Frankincense : Medicinal Uses -- Articles & patents

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**Frankincense : Medicinal Uses**



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[**http://en.wikipedia.org/wiki/Frankincense**](http://en.wikipedia.org/wiki/Frankincense)

**Frankincense   
[ Excerpt ]**

  
Frankincense, also called olibanum, is an aromatic resin obtained
from trees of the genus Boswellia, particularly Boswellia sacra,
B. carteri, B. thurifera, B. frereana and B. bhaw-dajiana
(Burseraceae). The English word is derived from Old French "franc
encens" (i.e., high quality incense)[1] and is used in incense and
perfumes.  
  
There are four main species of Boswellia that produce true
frankincense and resin from each of the four is available in
various grades. The grades depend on the time of harvesting. The
resin is hand-sorted for quality.  
  
Frankincense is mentioned in the Bible as one of the three gifts
the wise men gave to the young child Jesus.  
  

![](Frankincense.jpg)

**Description**  
Flowers and branches of the Boswellia sacra tree, the species from
which most frankincense is derived  
  

![](Boswelliasacra.jpg)

  
Frankincense is tapped from the scraggly but hardy trees by
slashing the bark, which is called striping, and allowing the
exuded resin to bleed out and harden. These hardened resins are
called tears. There are several species and varieties of
frankincense trees, each producing a slightly different type of
resin. Differences in soil and climate create even more diversity
of the resin, even within the same species. Boswellia Sacra trees
are considered unusual for their ability to grow in environments
so unforgiving that they sometimes grow out of solid rock. The
initial means of attachment to the rock is unknown but is
accomplished by a bulbous disk-like swelling of the trunk. This
growth prevents it from being ripped from the rock during violent
storms. This feature is slight or absent in trees grown in rocky
soil or gravel. The trees start producing resin when they are
about eight to 10 years old.[2] Tapping is done two to three times
a year with the final taps producing the best tears due to their
higher aromatic terpene, sesquiterpene and diterpene content.
Generally speaking, the more opaque resins are the best quality.
Fine resin is produced in Somalia and along the northern coast of
Somalia, from which the Roman Catholic Church draws its
supplies.[3]  
  
Recent studies have indicated that frankincense tree populations
are declining, partly due to over-exploitation. Heavily tapped
trees produce seeds that germinate at only 16% while seeds of
trees that had not been tapped germinate at more than 80%. In
addition, burning, grazing, and attacks by the longhorn beetle
have reduced the tree population.[4] Conversion (clearing) of
frankincense woodlands to agriculture is also a major
threat.[5]...  
  
**Traditional medicine**  
Boswellia sacra tree, from which frankincense is derived, growing
inside Biosphere 2  
  
Frankincense resin is edible and is used in traditional medicines
in Africa and Asia for digestion and healthy skin. For internal
consumption, it is recommended that frankincense be translucent,
with no black or brown impurities. It is often light yellow with a
(very) slight greenish tint. It is often chewed like gum, but it
is stickier.  
  
In Ayurvedic medicine frankincense (Boswellia serrata), commonly
referred to in India as "dhoop," has been used for hundreds of
years for treating arthritis, healing wounds, strengthening the
female hormone system and purifying the air. The use of
frankincense in Ayurveda is called "dhoopan". In Somali,
Ethiopian, Arabian, and Indian cultures, it is suggested that
burning frankincense daily in the house brings good health.[17]  
  
**Frankincense essential oil**  
**Frankincense (Boswellia carteri) essential oil**  
The essential oil of frankincense is produced by steam
distillation of the tree resin. The oil's chemical components are
75% monoterpenes, sesquiterpenes, monoterpenoles, sesquiterpenols,
and ketones. It has a good balsamic sweet fragrance, while the
Indian frankincense oil has a very fresh smell. Steam or hydro
distilled frankincense oil does contain a number of boswellic
acids (triterpenoids) which represents a method of validating the
authenticity of the essential oil. The chemistry of the essential
oil is mainly monoterpenes and sesquiterpenes with small amounts
of diterpenoid components being the upper limit in terms of
molecular weight.[18][19][20] Frank A, Unger M. J Chromatogr A.
2006 Apr 21;1112(1-2):255-62. Analysis of frankincense from
various Boswellia species with inhibitory activity on human drug
metabolising cytochrome P450 enzymes using liquid chromatography
mass spectrometry after automated on-line extraction.  
  
**Perfume**  
Olibanum is characterized by a balsamic-spicy, slightly lemon,
fragrance of incense, with a conifer-like undertone. It is used in
the perfume, cosmetic and pharmaceutical industries.  
  
**Medical research**  
For therapy trials in ulcerative colitis, asthma and rheumatoid
arthritis there are only isolated reports and pilot studies from
which there is not yet sufficient evidence of safety and efficacy.
Similarly, the long-term effects and side effects of taking
frankincense has not yet been scientifically investigated.
Nonetheless, several preliminary studies have been published.  
  
**Frankincense**  
A 2008 study reported that frankincense smoke was a psychoactive
drug that relieves depression and anxiety in mice.[21][22] The
researchers found that the chemical compound incensole acetate[23]
was responsible for the effects.[21]  
  
In a different study, an enriched extract of "Indian Frankincense"
(usually Boswellia serrata) was used in a randomized,
double-blinded, placebo-controlled study of patients with
osteoarthritis. Patients receiving the extract showed significant
improvement in their arthritis in as little as seven days. The
compound caused no major adverse effects and, according to the
study authors, is safe for human consumption and long-term
use.[24]  
  
In a study published in 2009, it was reported that "Frankincense
oil appears to distinguish cancerous from normal bladder cells and
suppress cancer cell viability."[25]  
  
A 2012 study in healthy volunteers determined that exposure to
11-keto-I2-boswellic acid (KBA), a lead boswellic acid in the novel
solubilized frankincense extract Boswelan, is increased when taken
with food. However, simulations based on a two-compartment
pharmacokinetic model with single first-order absorption phase
proposed that the observed food interaction loses its relevance
for the simulated repeated-dose scenario.[26]  
  
In a 2012 study, researchers found that the "behavioral effect [of
insensole actetate] was concomitant to reduced serum
corticosterone levels, dose-dependent down-regulation of
corticotropin releasing factor and up-regulation of brain derived
neurotrophic factor transcripts IV and VI expression in the
hippocampus. These data suggest that IA modulates the
hypothalamicapituitaryaadrenal (HPA) axis and influences
hippocampal gene expression, leading to beneficial behavioral
effects supporting its potential as a novel treatment of
depressive-like disorders."[27]  
  
In 2013, Leicester University researchers announced findings that
AKBA (acetyl-11-keto-beta-boswellic acid), a chemical compound in
the resin, has cancer-killing properties and has the potential to
destroy ovarian cancer cells. The lead researcher from the
University's Department of Cancer Studies and Molecular Medicine
announced the findings after a year studying the AKBA compound
with ovarian cancer cell lines in vitro that showed it is
effective at killing late stage cancer cells. Kamla Al-Salmani
noted that among surprising findings were that some cells that had
become resistant to chemotherapy were killed during the in vitro
study. The efficacy of AKBA as a potential medicine for treatment
of cancers(colon, breast and prostate) has been tested. The
results are based on the preliminary and unverified findings of
the laboratory study, which marked the first study to identify an
ability to fight ovarian cancer. It is in early stages and, as of
2014, yet to be published in a peer-reviewed journal.[28][29][30]  
  
**Chemical composition**  
These are some of the chemical compounds present in frankincense:  
  
"acid resin (56 per cent), soluble in alcohol and having the
formula C20H32O4"[31]  
gum (similar to gum arabic) 30a36%[31]  
3-acetyl-beta-boswellic acid (Boswellia sacra)[32]  
alpha-boswellic acid (Boswellia sacra)[32]  
4-O-methyl-glucuronic acid (Boswellia sacra)[32]  
incensole acetate  
phellandrene[31]  
  


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[**http://news.bbc.co.uk/2/hi/middle\_east/8505251.stm**](http://news.bbc.co.uk/2/hi/middle_east/8505251.stm)

**Frankincense: Could it be a cure for
cancer?**  
  
[ Excerpt ]

  
**Cancer hope**  
But immunologist Mahmoud Suhail is hoping to open a new chapter in
the history of frankincense.  
  
Scientists have observed that there is some agent within
frankincense which stops cancer spreading, and which induces
cancerous cells to close themselves down. He is trying to find out
what this is.  
  
"Cancer starts when the DNA code within the cell's nucleus becomes
corrupted," he says. "It seems frankincense has a re-set function.
It can tell the cell what the right DNA code should be.  
  
"Frankincense separates the 'brain' of the cancerous cell - the
nucleus - from the 'body' - the cytoplasm, and closes down the
nucleus to stop it reproducing corrupted DNA codes."  
  
Working with frankincense could revolutionise the treatment of
cancer. Currently, with chemotherapy, doctors blast the area
around a tumour to kill the cancer, but that also kills healthy
cells, and weakens the patient. Treatment with frankincense could
eradicate the cancerous cells alone and let the others live.  
  
The task now is to isolate the agent within frankincense which,
apparently, works this wonder. Some ingredients of frankincense
are allergenic, so you cannot give a patient the whole thing.  
  
Dr Suhail (who is originally from Iraq) has teamed up with medical
scientists from the University of Oklahoma for the task.  
  
In his laboratory in Salalah, he extracts the essential oil from
locally produced frankincense. Then, he separates the oil into its
constituent agents, such as Boswellic acid.  
  
"There are 17 active agents in frankincense essential oil," says
Dr Suhail. "We are using a process of elimination. We have cancer
sufferers - for example, a horse in South Africa - and we are
giving them tiny doses of each agent until we find the one which
works."  
  
"Some scientists think Boswellic acid is the key ingredient. But I
think this is wrong. Many other essential oils - like oil from
sandalwood - contain Boswellic acid, but they don't have this
effect on cancer cells. So we are starting afresh."  
  
The trials will take months to conduct and whatever results come
out of them will take longer still to be verified. But this is a
blink of the eye in the history of frankincense.   
  


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**References**

  
Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta
Med 2006; 72(12): 1100-16.  
  
Khajuria A, et al. Immunomodulatory activity of biopolymeric
fraction BOS 2000 from Boswellia serrata. Phytother Res 2008;
22(3): 340-8.  
  
Kirste S, et al. Boswellia serrata acts on cerebral edema in
patients irradiated for brain tumors: a prospective, randomized,
placebo-controlled, double-blind pilot trial. Cancer 2011;
117(16): 3788-95.  
  
Park B, et al. Boswellic acid suppresses growth and metastasis of
human pancreatic tumors in an orthotopic nude mouse model through
modulation of multiple targets. PLoS One. 2011; 6(10): e26943
[epub].  
  
Suhail MM, et al. Boswellia sacra essential oil induces tumor
cell-specific apoptosis and suppresses tumor aggressiveness in
cultured human breast cancer cells. BMC Complement Altern Med
2011; 11: 129.  
  
Takahashi M, et al. Boswellic acid exerts antitumor effects in
colorectal cancer cells by modulating expression of the let-7 and
miR-200 microRNA family. Carcinogenesis 2012; 33(12): 2441-9.  
  
Yuan Y, et al. Acetyl-11-keto-beta-boswellic acid (AKBA) prevents
human colonic adenocarcinoma growth through modulation of multiple
signaling pathways. Biochim Biophys Acta 2013; 1830(10): 4907-16.  
  
Zhang YS, et al. Acetyl-11-keto-A-boswellic acid (AKBA) inhibits
human gastric carcinoma growth through modulation of the
Wnt/A-catenin signaling pathway. Biochim Biophys Acta 2013;
1830(6): 3604-15.  
  


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[**http://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/news/2013-12-23-can-frankincense-really-fight-cancer/**](http://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/news/2013-12-23-can-frankincense-really-fight-cancer/)23 Dec 2013  
  

**Can frankincense really fight cancer?**

  
aFrankincense afights cancera,a is the festive health headline
from the Mail Online. The aaromatic substance from the Nativity
story could help treat ovarian tumours,a it says.  
  
The news is based on a University of Leicester press release
entitled aChristmas gift brings treatment hope for cancer
patientsa. Unfortunately, many more Christmases are likely to pass
before anyone is treated with frankincense for ovarian cancer.  
  
This is because the news is based on positive early findings from
research carried out on the AKBA compound found in frankincense
and ovarian cancer cells in a lab.  
  
The press release says the researchers have been able to show the
ability of the compound to combat cancer cells in late-stage
ovarian cancer.  
  
This is festive news, and the press team at the University of
Leicester should be congratulated for their ingenuity. However,
limited conclusions can be drawn from the preliminary findings of
this laboratory study as it is yet to be published in a
peer-reviewed journal. And some of the claims should not be taken
at face value; in particular the press releaseas claim that
frankincense has no known side effects. Such claims would need
rigorous scientific evaluation before they could be verified.  
  
This research is still at a very early stage and as the press
release points out, frankincense is yet to be studied for the
treatment of ovarian cancer in humans.  
  
**What is ovarian cancer?**  
Ovarian cancer affects more than 6,500 women in the UK each year
and is the fifth most common cancer among women. As the symptoms
of ovarian cancer can be similar to those of other conditions, it
can be difficult to recognise, particularly in the early stages of
the disease. However, there are early symptoms to look out for,
such as persistent bloating, pain in the pelvis and lower stomach,
and difficulty eating.  
   
**Why is this in the news?**  
The story is based on a press release from the University of
Leicester about the findings of a study carried out by researchers
from the University. The researchers looked at a compound derived
from frankincense called acetyl-11-keto-beta-boswellic acid (AKBA)
and ovarian cancer cells.  
  
The study has not yet been published in a peer reviewed scientific
journal, so the findings reported should be treated with caution.
With only the press release available it is not possible to fully
appraise the design and methods of this study.  
  
The study appears to have been carried out in the laboratory for
about a year and was funded by the Omani government. No other
study methods are provided.  
  
It is possible that the press release is being issued now because
of the link between frankincense and Christmas.  
  
 **What is frankincense?**  
Frankincense is a fragrant plant resin that comes from the
Boswelllia sacra tree found across Africa and the Arabian
peninsula, including Yemen and Oman. It is one of the famous gifts
said to have been given by the Wise Men when they visited newborn
Jesus.  
  
Frankincense has been used as a folk medicine for centuries due to
its anti-inflammatory properties. Previous studies have linked the
AKBA compound as a potential treatment for other cancers as well
as osteoarthritis.  
  
 **What are the reported study findings?**  
In the press release and accompanying audio interview, Dr Mark
Evans from the University of Leicester, who supervised the
research, says: aWe have shown that this frankincense compound is
effective at killing ovarian cancer cells at realistic
concentrations.  
  
aWhat has been most surprising is that the cells we have tested
which are resistant to chemotherapy have shown to be more
sensitive to this compound, suggesting frankincense may indeed be
able to help overcome drug resistance, and lead to an improved
survival rate for patients with late-stage ovarian cancera.  
  
 **Conclusion**  
Very little can be said, based on the preliminary and unverified
findings of this laboratory study. The study is yet to be
published in a peer-reviewed journal and until this happens, it is
worth exercising a little healthy scepticism about the claims
being made and the time of year they are being made in. This
research is still at a very early stage and as the press release
points out, frankincense is yet to be studied for the treatment of
ovarian cancer in humans.  
  
The findings of this preliminary research do not affect the
current methods for treating ovarian cancer.  
  
**Links To The Headlines**  
Frankincense 'fights cancer': Aromatic substance from the Nativity
story could help treat ovarian tumours. Daily Mail. December 20
2013[**http://www.dailymail.co.uk/health/article-2526816/Frankincense-fights-cancer-Aromatic-substance-Nativity-story-help-treat-ovarian-tumours.html**](http://www.dailymail.co.uk/health/article-2526816/Frankincense-fights-cancer-Aromatic-substance-Nativity-story-help-treat-ovarian-tumours.html)  
  


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[**http://theresanoilforthat.blogspot.com/2012/02/frankincense-and-cancer.html**](http://theresanoilforthat.blogspot.com/2012/02/frankincense-and-cancer.html)

**Frankincense and Cancer**  
  
[ Excerpt ]

  
In a study published in March 2009 by the University of
Oklahoma Health Sciences Center it was reported
that"Frankincense oil appears to distinguish cancerous from
normal bladder cells and suppress cancer cell viability  
  
**Study: Frankincense may fight some cancers****January 31, 2006**A Virginia Tech scientist says frankincense oil might be
useful in treating malignant melanoma -- an aggressive cancer
that attacks humans and equines.  
  
Approximately 54,000 malignant melanoma cases are diagnosed
annually, according to the American Cancer Society, and there
are many similarities between malignant melanoma in horses and
malignant melanoma in people.  
  
Recognizing the opportunity for translational research, John
Robertson, a professor in the Virginia-Maryland Regional
College of Veterinary Medicine at Virginia Tech, has been
studying the disease and an experimental treatment involving
frankincense oil.  
  
Frankincense is a botanical oil distillate made from fermented
plants that contains boswellic acid, a component known to have
anti-neoplastic properties.  
  
During a recent presentation before a regional meeting of the
American Cancer Society in Roanoke, Va., Robertson -- director
of the college's Center for Comparative Oncology -- said he's
found the oil has fairly selective anti-tumor activity and
doesn't appear to disrupt normal cells."I think this research
on frankincense oil suggests that this ancient medicine may
have significant modern uses for chemotherapy of
non-resectable malignancies," said Robertson.  
  


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**<http://gulfnews.com/news/gulf/oman/oman-researchers-find-cancer-treatment-in-frankincense-1.1251>940**Muscat: Omani researchers at the University of Nizwa have
succeeded in producing a medicinally important compound from
Omani frankincense, luban, for breast cancer treatment.  
  
Dr Ahmad Sulaiman Al Harrasi, holder of the Universityas Chair
of Omanas Medicinal Plants and Marine Natural Products, said
researchers have succeeded in isolating and enhancing the
percentage of AKBA found in the resin of Omani frankincense.  
  
AKBA (beta-boswellic acid, keto-beta-boswellic acid, and
acetyl-keto-beta-boswellic acid) has been indicated in
apoptosis, or death of cancer cells, in particular brain
tumours and cells affected by leukaemia or colon cancer.  
  
Dr Al Harrasi pointed out that the research was done under the
chairmanship of Oman Medicinal Plants and Marine Natural
Products at the Nizwa University and was funded jointly by the
Oman Research Council and Nizwa University,  
  
This discovery, the Nizwa University scientist says, will play
a vital medicinal as well as economic role. aAKBA is very
costly,a he said, explaining the economic benefits to the
country.  
  
Omani media have claimed that a acurea for cancer had been
found, which Al Harrasi denies.  
  
aWe would like to dispel certain misgivings regarding our
discovery,a Dr Al Harrasi told Gulf News over the phone from
Nizwa, about 160km northwest of Muscat.  
  
aWe have not discovered a breast cancer cure and it is not
from oil as reported in some media and being circulated on
WhatsApp as well as social media,a he added  
  
The Assistant Dean for Scientific Studies and Research in
Nizwa University also clarified that the compound had not been
tested on humans. aWe experimented on various cancer cell
alliances for our research,a he clarified, adding that their
experiments on several cancer cells showed positive results.  
  
He also revealed that patent registration process was under
process and 60 to 70 per cent of work was done. aThe draft
[for patent] has been accepted,a he said  
  


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[**http://ecancer.org/news/465.php**](http://ecancer.org/news/465.php)

**Frankincense oil derived from Boswellia
carteri induces bladder tumor cell specific cytotoxicity**

**18 Mar 2009**  
**Frankincense oil - a potential treatment option for bladder
cancer**  
An enriched extract of the Somalian Frankincense herb
Boswellia carteri has been shown to kill off bladder cancer
cells. Frankincense oil is prepared from aromatic hardened gum
resins obtained by tapping Boswellia trees. One of the main
components of frankincense oil is boswellic acid, a component
known to have anti-neoplastic properties. Research presented
in the peer reviewed journal, BMC Complementary and
Alternative Medicine found that  Frankincense oil might
represent an alternative intravesical agent for bladder cancer
treatment.  
  
HK Lin and his team, from the University of Oklahoma Health
Sciences Center and Oklahoma City VA Medical Center, set out
to evaluate frankincense oil for its anti-tumour activity in
bladder cancer cells. The authors investigated the effects of
the oil in two different types of cells in culture: human
bladder cancer cells and normal bladder cells. The team found
that frankincense oil is able to discriminate between normal
and cancerous bladder cells in culture, and specifically kill
cancer cells.  
  
Within a range of concentration, frankincense oil suppressed
cell viability in bladder transitional carcinoma J82 cells but
not in UROtsa cells. Comprehensive gene expression analysis
confirmed that frankincense oil activates genes that are
responsible for cell cycle arrest, cell growth suppression,
and apoptosis in J82 cells. However, frankincense oil-induced
cell death in J82 cells did not result in DNA fragmentation, a
hallmark of apoptosis.  
  
Article: Frankincense oil derived from Boswellia carteri
induces tumor cell specific cytotoxicity  
Mark Barton Frank, Qing Yang, Jeanette Osban, Joseph T
Azzarello, Marcia R Saban, Ricardo Saban, Richard A Ashley,
Jan C Welter, Kar-Ming Fung and Hsueh-Kung Lin
http://www.biomedcentral.com/bmccomplementalternmed/  
  


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**VIDEO**

  
[**http://www.youtube.com/watch?v=hsJg\_kmvQDE?**](http://www.youtube.com/watch?v=hsJg_kmvQDE?)  
> FRANKINCENSE FOR CANCER - PRE CLINICAL RESULTS

  
[**http://kfor.com/2013/04/30/the-biblical-cure/**](http://kfor.com/2013/04/30/the-biblical-cure/)  
> Frankincense: The Biblical cure? | KFOR.com

  


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**PATENTS**

**Novel Salts Of Boswellic Acids And Selectively Enriched
Boswellic Acids And Processes For The Same****US2013116211**  
  
New salts or ion-pair complexes obtained by a reaction between
boswellic acids or selectively enriched
3-O-acetyl-11-keto-beta-boswellic acid (AKBA) or
11-keto-beta-boswellic acid (KBA) compounds obtained through a
new improved process, and an organic amine, more particularly
with glucosamine. These salts or ion pair complexes are useful
in nutraceuticals and in food supplements for
anti-inflammatory and analgesic treatment of joints and cancer
prevention or cancer therapeutic agents. These salts or ion
pair complexes could also be used in cosmetic or
pharmaceutical composition for external treatment of body
parts or organs to treat inflammatory diseases or cancer.  
  
[0001] This invention relates to novel salts or ion pair
complexes of substituted/unsubstituted boswellic acid with
certain organic bases particularly though not exclusively with
glucosamine. This invention also includes an improved process
for selectively enriching 3-O-acetyl-11-keto-[beta]-boswellic
acid and 11-keto-[beta]-boswellic acid hereinafter referred as
(AKBA) and (KBA) respectively from an extract containing a
mixture of boswellic acids.  
  
**BACKGROUND ART**  
[0002] Inflammation is a critical protective biological
process triggered by irritation, injury or infection,
characterized by redness and heat, swelling, loss of function
and pain. In addition to the foregoing induced conditions,
inflammation can also occur due to age related factors. Life
expectancy of general population has increased dramatically
during the past few decades due to efficient control of
infectious diseases and better access to nutritious food. This
positive enhancement in life span coupled with changing
environmental conditions elevated the incidence of chronic
age-related diseases such as arthritis, diabetes, cancer,
cardiovascular diseases, etc. Chronic inflammatory condition
and cancer have become emerging health concerns in a number of
countries across the globe and for people among all cultures.
Arthritis is one of the most debilitating diseases of modem
times. The quality of life for sufferers of these two diseases
and their families is severely affected. Non-steroidal
anti-inflammatory drugs are most commonly used remedies for
rheumatic diseases. Presently, there has been a tremendous
surge in demand for natural non-steroidal anti-inflammatory
drugs (NSAIDs) because of their established safety and
efficacy, through decades of usage by various cultures.  
  
[0003] The inflammatory and carcinogenesis processes are known
to be triggered by increased metabolic activity of arachidonic
acid. Arachidonic acid diverges down into two main pathways
during this process, the cyclooxygenase (COX) and lipoxygenase
(LOX) pathways. The COX pathways lead to prostaglandin and
thromboxane production and the LOX pathways leads to
leukotrienes (LTS) and hydroxyl eicosatetetraenoic acid
(HETEs). These classes of inflammatory molecules exert
profound biological effects, which enhance the development and
progression of human cancers,  
  
[0004] Leukotrienes and 5(S)-HETE are important mediators for
inflammatory, allergic and obstructive process. Leukotrienes
increase micro vascular permeability and are potent
chemotactic agents. Inhibition of 5-lipoxygenase indirectly
reduces the expression of TNF-[alpha] (a cytokine that plays a
key role in inflammation). 5-Lipoxygenase is therefore the
target enzyme for identifying inhibitors, which have potential
to cope with a variety of inflammations and
hypersensitivity-based human diseases including asthma,
arthritis, bowel diseases such as ulcerative colitis and
circulatory disorders such as shock and ischaemia.  
  
[0005] Similarly prostaglandins are intercellular messengers
that are produced in high concentration at the sites of
chronic inflammation and are capable of causing vasodilation,
increased vascular permeability and sensitizing pain
receptors. The pro-inflammatory prostaglandins (PGE2) are
produced by inducible isoform cyclooxygenase-2 (COX-2). The
prostaglandins that are important in gastrointestinal and
renal function are produced by the constitutively expressed
isoform, cyclooxygenase-1 (COX-1). COX-1 is the protective
housekeeper isoform and it regulates mucosal cell production
of mucous that provides a barrier between the acid and pepsin
present in gastric secretions. Non-selective COX inhibitors
thus produce serious side effects. Scientists around the world
are thus investing a major effort in identifying non-steroidal
anti-inflammatory drugs that inhibit 5-lipoxygenase and
cyclooxygenase-2 enzymes. As both COX-2 and 5-LOX are commonly
expressed in any kind of inflammatory condition, efforts are
currently being focused to obtain the so called dual acting
anti-inflammatory drugs that are able to inhibit both COX-2
and 5-LOX enzymes. Unfortunately, the odds of finding a new
dual acting natural NSAID that can truly alleviate the
symptoms of inflammatory diseases are very thin. Hence, the
researchers conceived the idea that using a combination of
drugs, one having the COX-2 inhibitory activity and the other
having 5-LOX inhibitory activity, as the next best option.  
  
[0006] Rheumatoid arthritis is a chronic inflammatory
condition that affects the lubricating mechanism and
cushioning of joints. As a result of this autoimmune disease
the bone surfaces are destroyed, which leads to stiffness,
swelling, fatigue and crippling pain. Osteoarthritis is the
common form of arthritis and results primarily from
progressive degeneration of cartilage glycoaminoglycons. The
damage is often compounded by a diminished ability to restore
and repair joint structures including cartilage. The smooth
surface of the cartilage becomes hard and rough creating
friction. As a result of this the joint gets deformed, painful
and stiff. Studies have indicated that over 40 million
Americans have osteoarthritis, including 80% of persons over
the age of 50. The major focus for osteoarthritis treatment,
should therefore involve agents that not only stimulate the
production of biological substances necessary for regeneration
of cartilage cells and proper joint function but also diminish
pain inflammation.  
  
[0007] It is therefore an object of the present invention to
provide a salt or ion pair complex as a dietary supplement,
that exhibits anti-arthritic properties without deleterious
side effects.  
  
**[0008] Boswellic Acids**  
[0009] Gum resin of Boswellia species known as Indian
frankincense has been used as an anti-inflammatory agent in
Traditional Ayurvedic Medicine in India. Ancient Ayurvedic
texts described its therapeutic use. Clinical trails performed
by CSIR laboratories in India have shown fair to excellent
results in 88% of the patients, with no adverse side effects
(Singh, G. B., Status report, anti-inflammatory drugs from
plant sources, 1982). A randomized, double blind, placebo
controlled clinical trials on patients with osteo-arthritis of
knee exhibited statistically significant improvement in the
pain, decreased swelling and increased knee flexion etc.
(Kimmatkar, Phytomedicine, 2003, 10, 3-7), The therapeutic
effects shown by Boswellia serrata extract were comparable to
those exhibited by sulfasalazine and mesalazine in patients
with ulcerative colitis. (Gupta, I., et al., Eur. J. Med.
Res., 1998, 3, 511-14 and Gerhardt, H., et. al.,
Gastroenterol., 2001, 39, 11-17). The source of
anti-inflammatory actions has been attributed to boswellic
acids (Safayhi, H., et al., Planta Medica, 1997, 63, 487-493
and J. Pharmacol. Exp. Ther., 1992, 261, 1143-46, both the
journals published from USA), a group of triterpene acids
isolated from the Boswellia resin (Pardhy, R. S., et al.,
Indian J. Chem., 1978, 16B, 176-178). These compounds exert
anti-inflammatory activity by inhibiting 5-lipoxygenase
(5-LOX). The boswellic acids also gained prominence recently
for their antiproliferative actions. Boswellic acids inhibited
several leukemia cell lines in vitro and inhibited melanoma
growth and induced apoptosis (Hostanska, K., et al.,
Anticancer Res., 2002, 22(5), 2853 -62). The acetyl boswellic
acids were found to be unique class of dual inhibitors of
human topoisomerases I and II a (Syrovets, T. et al., Mol.
Pharmacol., 2000, 58(1), 71-81). Immunomodulatory activity of
boswellic acids had been reported by Sharma et al. in
Phytotheraphy Research, 1996, 10, 107-112, published from USA.
A detailed study on the structural requirements for boswellic
acids indicated that of all the six acids,
3-O-acetyl-11-keto-[beta]-boswellic acid, hereinafter
referenced as AKBA shows most pronounced inhibitory activity
against 5-LOX (Sailer, E. R., et al., British J. Pharmacology,
1996, 117, 615-618). AKBA acts by unique mechanism, in which
it binds to 5-LOX in a calcium-dependent and reversible manner
and acts as a non-redox-type, non-competitive inhibitor
(Sailer, E. R., et al., Eur. J. Biochem., 1998, 256, 364-368).
The AKBA or a plant extract or composition containing it was
reported to be effective for topical application, as an agent
to soften lines and/or relax the skin (Alain, M., et. al.,
U.S. patent application No. 2004/0166178, dated Aug. 26,
2004). AKBA has thus become the subject of intensive research
for its potential for the treatment of chronic inflammatory
disorders.  
  
**[0010] Glucosamine**  
[0011] Glucosamine is a natural substance found in high
quantities in joint structures. The main function of
glucosamine in joint structures is to produce cartilage
components necessary for maintaining and repair joint tissue.
Glucosamine stimulates the formation of joint structural
components such as collagen, the protein of the fibrous
substances that holds the joints together and helps to
build-up the cartilage matrix, Collagen is the main component
of the shock-absorbing cushion called articular cartilage. It
is also a necessary nutrient in the production of synovial
fluid. Some people may lose the ability with age to produce
glucosamine, thereby inhibiting the grpwth of cartilage
destroyed during wear and tear in osteoarthritis patients
(Towheed, T. E., Arthritis and Rheumatism, 2003, 49, 601-604).
When taken orally as a dietary supplement in the form of
glucosamine sulfate, it has been shown to exert protective
effect against joint destruction and is selectively used by
joint tissues to promote healthy joint function and show
potential therapeutic effect in osteoarthritis (Perry, G. H.,
et al., Ann. Rheum. Dis., 1972, 31, 440-448).  
  
[0012] Several double-blind studies with glucosamine sulfate
showed therapeutic effects comparable to or even better than
non steroidal anti-inflammatory drugs in relieving the
symptoms of osteoarthritis (Vaz, A. L., Curr. Med, Res. Opin.,
1982, 8, 145-149; D'Ambrosia, E. D., et al.,
Pharmatherapeutica, 1982, 2, 504-508 and Tapadinhas, M. J., et
al., Pharmatherapeutica, 1982, 3, 157-168). The NSAIDs offer
only symptomatic relief, whereas glucosamine addresses the
root cause of osteoarthritis disease. It support body's
natural ability to tackle the disease on its own by providing
the building blocks to many structural components such as
glucosaminoglycons to repair the damage caused by
osteoarthritis. Glucosamine hydrochloride is used for this
study.  
  
**DISCLOSURE OF THE INVENTION**  
[0013] The organic solvent extract of the gum resin of
Boswellia serrata contain a total of six boswellic acids and
two timcallic acids. These acids are shown in FIG. 1, and are
represented by B1, B2, B3, B4, B5, B6, T1, T2 and T3. Studies
have indicated AKBA as the most potent an anti-inflammatory
agent among all the boswellic acids. The concentration of
AKBA, indicated as B2 in the FIG. 1, amounts only in the range
of 1-10% in the extract, but most often it is in the range of
2-3%. The potential usefulness of boswellic acids in general
and AKBA in particular can be a great incentive to take-up
further development of these compounds in all possible
aspects.  
  
[0014] The present invention is aimed at selective enrichment
of active compounds, KBA and AKBA to a therapeutically useful
range such as 30% to 100% from natural Boswellia extract using
a new improved process and then converting the enriched
compounds to a salt or ion pair complex with enhanced
solubility and improved therapeutic efficacy for use as an
anti-arthritic dietary supplement. The salt or ion pair
combination may be accomplished by using an acid function of
the boswellic acid and an amine function from amino organic
compounds, especially glucosamine.  
  
[0015] The enrichment of AKBA from natural Boswellia extract
was already described in international patent application (PCT
#WO 03/074063, dated. 12th September 2003) and also in US
patents (application #20030199581, publication dated 23 Oct.
2003 and application #20040073060, publication dated 15 Apr.
2004). The processes described in these patents involve
multi-step procedures and requires tedious work-up and
chromatographic purifications. The present invention is an
improved method, where in the acetylation and allylic
oxidation steps are conducted in a single pot. This process
eliminates the need for labor-intensive work-up following
acetylation and time consuming product drying before
proceeding to the oxidation step, as required by the processes
reported in the patents and journal articles. This process
also efficiently utilizes the un-reacted pyridine and acetic
anhydride from the acetylation step to form highly active
oxidizing systems such as CrO3/pyridine and CrO3/acetic
anhydride. The present invention effectively reduces the
overall reaction time for peracetylation and the oxidation
steps. The new process eliminates the presence of possible
chromium impurities in the KBA/AKBA enriched (30-40%) product
by acid/base treatment without any need for chromatography.  
  
[0016] A fraction enriched to 30-40% 11-keto-[beta]-boswellic
acid (KBA), can be accomplished by subjecting the crude
mixture to basic treatment, followed by filtration and
acidification of the mother liquor, and then separation of the
white solid by filtration and drying, It was then reacetylated
to obtain 30-40% AKBA enriched fraction, The fractions
enriched to higher percentage (40-100%) of KBA and AKBA can be
obtained by applying chromatographic methodology on hydrolysis
mixture and re-acetylation mixture, respectively.  
  
[0017] An ionic salt or ion pair complex of boswellic acids
containing AKBA in the range of 5 to 100% can be obtained by
using appropriately enhanced boswellic compound and a suitable
amine compound and adopting the representative procedure given
in the examples.  
  
[0018] This invention relates to novel salts or ion pair
complexes of boswellic acid and keto boswellic acid and acetyl
keto boswellic acid with glucosamine having the following
general formula.  
  
wherein R1 and R2 are H or taken together to form a keto
group;  
R3 is H or acyl group;  
X is an heterocyclic base or an organic bases represented by
NHR4R5R6:  
wherein R4, R5 and R6, are H or substituted or unsubtituted
lower or higher  
alkyl group or aryl group or cyclic alkyl group.  
  
[0024] Wherein the organic bases are glucosamine
(2-amino-2-deoxy-D-glucose), nicotinamide
(3-pyridinecarboxamide), pyridoxins
(5-hydroxy-6-methyl-3,4-pyridinedimethanol), caffeine
(3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dxone), creatine
(N-(aminoiminomethyl)-N-methylglycine), allantoin
(2,5-dioxo-4-imidazolidinyl)urea), Theobromine
(3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione), theophylline
(3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione), mesalamine
(5-amino-2-hydroxybenzoic acid), enfenamic acid
(2-[(2-phenylethyl)amino]benzoic acid), etofenamate
(2-[[3-(trifluoromethyl)phenyl]-amino]benzoic acid
2-(2-hydroxyethoxyethyl ester), flufenamic acid
(2-[[3-(trifluoromethyl)phenyl]amino]benzoic acid),
meclofenamic acid
(2-[(2,6-dichloro-3-methylphenyl)amino]benzoic acid),
mefenamic acid (2-[(2,3-dimethylphenyl)-amino]benzoic acid),
niflumic acid
(2-[[3-(trifluoromethyl)phenyl]-amino]-3-pyridinecarboxylic
acid), talniflumate
(2-[[3-(trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic
acid 1,3-dihydro-3-oxo-1-isobenzofuranyl ester), terofenamate
(2-[(2,6-dichloro-3-methylphenyl)-amino]benzoic acid
ethoxymethyl ester), tolfenamic acid
(2-[(3-chloro-2-methylphenyl)-amino]benzoic acid),
S-adenosylmethionine
((3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine
inner salt), 3-amino-4-hydroxybutyric acid, amixetrine
(1[2-(3-methylbutoxy)-2-phenylethyl]pyrrolidine), benzydamine
(N,N-dimethyl-3-[[1-(phenylmethyl)-1H-indazol-3-yl]oxy]-1-propanamine),
difenpiramide (N-2-pyridinyl-[1,1'-biphenyl]-4-acetamide),
ditazol (2,2'-[(4,5-diphenyl-2-oxazolyl)imino]-bisethanol),
emorfazone
(4-ethoxy-2-methyl-5-(4-morpholinyl)-3(2H)-pyridazinone),
fepradinol ((+-)-[alpha]-[[(2-hydroxy-1,
1-dimethylethyl)-amino]methyl]benzeneniethanol), paranyline
(4-(9H-fluoren-9-ylidenemethyl)benzene-carboximidamide),
perisoxal
([alpha]-(5-phenyl-3-isoxazolyl)-1-piperidineethanol).  
  
[0025] We have disclosed a simple method by which salts or
ion-pair complexes of boswellic acids with hetero-atom bases
(also referred to as 'organic base') can be made for their
inclusion in dietary or pharmaceutical compositions that
provide reduction in inflammation and other health benefits.
These salts or ion pair complexes are made by simple acid-base
reaction, as shown in eq, 1, between an organic acid (RCOOH)
and an organic base (NR4R5R6).  
  
RCOOH+NR4R5R6->RCOO<-+>NHR4R5R6 (equation 1)  
  
[0026] The new composition according to this invention may be
prepared by the following processes:  
  
(a) By reacting boswellic acids or ketoboswellic acid or
acetyl ketoboswellic acid with organic base.  
(b) By in situ generation of organic free base and reacting
with boswellic acids or ketoboswellic acid or acetyl
ketoboswellic acid.  
  
[0029] In the first process, stoichiometric equivalents of the
reactants are mixed to obtain the desired salts or ion pair
complexes. Preferably, the reaction is initiated by the slow
addition of organic free base, particularly, glucosamine free
base to an aqueous methanolic solution of boswellic acids.
Boswellic acids (48% by HPLC) may be obtained by a known
process of extraction from the gum resin of Boswellia serrata.
Glucosamine free base may be liberated from glucosamine
hydrochloride by anionic exchange resin treatment. The
enriched 11-ketoboswellic acid or 3-O-acetyl-11-ketoboswellic
acid (30%-100%) was obtained from the gum-resin of Boswellia
serrata using an improved method described herein.  
  
[0030] The salts or pair complexes prepared by this process
may contain between 10 to 70% of boswellic acids. 5-40% of
glucosamine.  
  
[0031] According to the second process of preparing the
compounds of this invention, stoichiometric quantities of
boswellic acids, potassium hydroxide and organic base salts,
particularly, glucosamine hydrochloride are reacted in aqueous
methanol medium.  
  
[0032] A further aspect of the present invention is a
pharmaceutical formulation comprising a compound as described
above in a pharmaceutically acceptable carrier (e.g., an
aqueous or a non aqueous carrier).  
  
[0033] A still further aspect of the present invention is a
method of treating inflammatory diseases, comprising
administering to a human or animal subject in need thereof a
treatment effective amount (e.g., an amount effective to
treat, slow the progression of, etc.) of a compound as
described above.  
  
[0034] Preferred embodiments relating to the improved process
of enriching AKBA in natural Boswellia extract and making the
salts or ion pair complexes are presented in examples 1 to 6.  
  
[0035] Though the following examples describe a specific
embodiment of this invention, obvious equivalents and
modifications known to persons skilled in the art are not
excluded from the scope of the appended claims.  
  
**EXAMPLE 1**  
**Isolation of 11-keto-[beta]-boswellic acid and
3-O-acetyl-11-keto-[beta]-boswellic acid**  
[0036] 1a). Single Pot Conversion of Boswellia Extract into
AKBA Enriched Fraction:  
  
[0037] To a solution of Boswellia serrata extract (85%, 10
kg,) in pyridine (5.4 L), in a 100 L all glass reactor
equipped with a water-cooled reflux condenser, was added
acetic anhydride (4.2 L) at room temperature and the mixture
was subjected to heating at 60-65[deg.] C. under stirring.
After 3 h, the mixture was cooled to ambient temperature and
diluted with acetic acid (24 L) and acetic anhydride (24 L).
The contents were cooled and treated slowly with chromium
trioxide (6.4 kg) while maintaining the temperature under
40[deg.] C. The stirring was continued for another 2 h after
the addition, and then the mixture was poured into ice water
and the contents were mixed thoroughly. The solid was
filtered, washed with water and dried in a vacuum oven to
obtain a residue (14 kg). The HPLC analysis of the crude
product showed complete conversion of boswellic acids B1, B4
and B6 to B2 (AKBA).  
  
[0038] 1b). Isolation of 30-40%
3-O-acetyl-11-keto-[beta]-boswellic acid: The above crude
reaction mixture (5 kg) was added to 4N hydrochloric acid (45
L) and heated at 60[deg.] C. for 4 h. The mixture was cooled
to ambient temperature and filtered. The precipitate was
washed with 4N HCl, followed by water and dried in a vacuum
oven to obtain AKBA enriched to 30-40% (2.8 kg).  
  
[0039] 1c). Isolation of 3-O-acetyl-11-keto-[beta]-boswellic
acid: The above, enriched compound (500 g) was subjected to
silica column chromatography using 5% to 30% ethyl
acetate/hexane mixtures. The fractions were monitored by TLC
and those containing AKBA (30%-60%) were combined and
subjected crystallization in hexane and ethyl acetate mixtures
to obtain fractions enriched up to 85% AKBA, Repeated
crystallization in the same solvent system yielded AKBA
enriched up to 100%.  
  
[0040] 1d). Isolation of 11-keto-[beta]-bowellic acid:
Alternatively, the crude mixture was dissolved in methanol and
subjected to base treatment (8N KOH), The precipitate was
separated by filtration and discarded. The mother liquor was
acidified and the off-white precipitate was filtered, washed
with water and dried under vacuum to obtain 30-40%
ketoboswellic acid (KBA). The 11-keto-[beta]-boswellic acid
mixture (200 g) obtained was adsorbed on 250 g of silica gel
and subjected column chromatography over 500 g of silica. The
column was eluted with hexane, 10% ethyl acetate/hexane, 20%
ethyl acetate/hexane and 30% ethyl acetate/hexane mixtures.
The fractions were monitored by TLC and the fractions
containing 11-keto-p-boswellic acid were combined and
evaporated and the residue was subjected to repeated
crystallization from ethyl/hexane mixtures to obtain pure
11-keto-[beta]-boswellic acid (45 g, 95-100%. purity).  
  
[0041] 1e). In a further variation of the process mentioned in
example 1a, the addition of acetic anhydride was eliminated.
Instead the peracetylated mixture was diluted with 20 L of
acetic acid and treated with CrO3 (6.4 kg) in 100 L of acetic
acid. The reaction mixture was quenched with excess water
after 24 h, and processed as described in example 1a,  
  
**EXAMPLE 2**  
[0042] Glucosamine salt of boswellic acids; To a solution of
boswellic acids (2 g, 48% boswellic acids) in 95% aqueous
methanol (50 mL) was added glucosamine free base solution (8.6
mL, 0.4 g) and stirred at rt for 1 h. Then the solvent was
evaporated under reduced pressure and dried to give
glucosamine salt or ion pair complex of boswellic acids as
gray colour powder (2.3 g), pH, 6,3, soluble in 90% aqueous
methanol.  
  
[0043] The analytical characteristics of the glucosamine salt
or ion pair complex of boswellic acids thus obtained are, B1,
4.75%, B2, 2,10%, B3, 5.44%, B4, 14.91%, B5, 2.18%, B6, 8.66%;
total: 38.04%; glucosamine (as free base) is 8.52%.  
  
**EXAMPLE 3**  
[0044] Glucosamine salt of boswellic acids (KCl): To a
solution of boswellic acids (5 g, 48% boswellic acids) in
methanol (125 mL) was added a solution of glucosamine
hydrochloride (2 g) in water (8 mL) and stirred at rt for 15
min. Then potassium hydroxide (0.52 g, 20% aqueous solution,
2.6 mL) was charged slowly for 10 min and the solution was
stirred at rt for 1 h. The solvent was evaporated under
reduced pressure and dried to give glucosamine salt or ion
pair complex of boswellic acids as gray colour powder (7.5 g),
pH, 6.8, soluble in 90% aqueous methanol.  
  
[0045] The analytical characteristics of the glucosamine salt
or ion pair complex of boswellic acids thus obtained are, B1,
4.04%, B2, 1.86%, B3, 4.65%, B4, 12.73%, B5, 1.76%, B6, 7.34%;
total: 32.38%; glucosamine (as free base) is 12.44%.  
  
**EXAMPLE 4**  
[0046] Glucosamine salt of boswellic acids (KCl): To a
solution of boswellic acids (5 g, 48% boswellic acids) in
methanol (125 mL) was added a solution of glucosamine
hydrochloride (4g) in water (11 mL) and stirred at rt for 15
min. Then potassium hydroxide (0.52 g, 20% aqueous solution,
2.6 mL) was charged slowly for 10 min and the solution was
stirred at rt for 1 h. The solvent was evaporated under
reduced pressure and dried to give glucosamine salt or ion
pair complex of boswellic acids as gray colour powder (9.6 g),
pH, 6.6, soluble in 90% aqueous methanol.  
  
[0047] The analytical characteristics of the glucosamine salt
or ion pair complex of boswellic acids thus obtained are, B1,
3.14%, B2, 1.37%, B3, 3.36%, B4, 9.75%, B5, 0.93%, B6, 4.76%;
total: 23.31%; glucosamine (as free base) is 27.16%.  
  
**EXAMPLE 5**  
[0048] Glucosamine salt of Acetyl ketoboswellic acid (KCl); To
a solution of acetyl ketoboswellic acid (5 g, 30% AKBA) in
methanol (100 mL) was added a solution of glucosamine
hydrochloride (0.63 g) in water (3 mL) and stirred at rt for
15 min. Then potassium hydroxide (0.164 g, 20% aqueous
solution, 0,82 mL) was charged slowly for 10 min and the
solution was stirred at rt for 1 h. The solvent was evaporated
under reduced pressure and dried to give glucosamine salt or
ion pair complex of acetyl ketoboswellic acid as gray colour
powder (4.8 g), pH, 6.7, soluble in 90% aqueous methanol.  
  
[0049] The analytical characteristics of the glucosamine salt
or ion pair complex of acetyl ketoboswellic acid thus obtained
are, AKBA is 27.68%; glucosamine (as free base) is 5.42%.  
  
**EXAMPLE 6**  
[0050] Glucosamine salt of Acetyl ketoboswellic acid (KCl): To
a solution of acetyl ketoboswellic acid (5 g, 30% AKBA) in
methanol (100 mL) was added a solution of glucosamine
hydrochloride (5 g) in water (15 mL) and stirred at rt for 15
min. Then potassium hydroxide (0.2 g, 20% aqueous solution,
1.0 mL) was charged slowly for 10 min and the solution was
stirred at rt for 1 h. The solvent was evaporated under
reduced pressure and dried to give glucosamine salt or ion
complex of acetyl ketoboswellic acid as gray colour powder
(9.3 g), pH, 5.6, soluble in 90% aqueous methanol.  
  
[0051] The analytical characteristics of the glucosamine salt
or ion pair complex of acetyl ketoboswellic acid thus obtained
are, AKBA is 15.30%; glucosamine (as free base) is 39.44%.  
  


---

  

**Novel anti-cancer purely natural
medicine (11-carbonyl-beta-acetyl boswellic acid)**  
**CN101724005**

  
The invention relates to a novel broad spectrum purely natural
medicine that can specifically inhibit phosphorylation of
protein T-kappa-B to prevent nuclear transport of T-kappa-B so
as to inhibit the growth of cancer cell, thereby treating
cancer. The novel medicine is a natural extractive, and has
the advantages of low production cost, high curative effect
and less side effect.  
  


---

  

**COMPOSITIONS AND METHODS FOR TREATING
AND PREVENTING INFLAMMATORY AND/OR DEGENERATIVE PROCESSES
IN HUMANS AND OTHER ANIMALS**  
**WO2007011674**

  
Disclosed are compositions useful for treating Alzheimer's
disease, atherosclerosis, arteriosclerosis, osteoarthritis and
other degenerative joint diseases, Huntington's chorea,
Parkinson's disease, optic atrophy, retinitis pigmentosa,
macular degeneration, muscular dystrophy, aging-associated
degenerative processes, asthma, dermatitis, laminitis,
pemphigoid, pemphigus, reactive airway disease (e.g., COPD,
IAD), inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis) , multiple sclerosis, rheumatoid
arthritis, periodontal disease, systemic lupus erythematosus,
sarcoidosis, psoriasis, type I diabetes, ischemia-reperfusion
injury, chronic inflammatory diseases, geriatric wasting,
cancer cachexia, cachexia associated with chronic
inflammation, sick feeling syndrome, and other inflammatory
and/or degenerative diseases, disorders, conditions,; and
processes in humans and other animals. In one embodiment, the
compositions include at least 4 of the following: a MMPl
inhibitor, a MMP2 inhibitor, a MMP3 inhibitor, a MMP7
inhibitor, a MMP9 inhibitor, an ADAMTS-4 inhibitor, a MMP13
inhibitor, and a MMP14 inhibitor. In another embodiment, the
compositions include a curcuminoid, a polymethoxylated
flavone, a catechin, and a boswellic acid.  
  


---

  

**WATER SOLUBLE BOSWELLIC ACIDS, THEIR
PREPARATION AND USE FOR TREATING IMFLAMMATORY
CONDITION**  
**WO02066491**

  
A new composition which can be formed through a method
comprising: (a) dissolving mixtures of boswellic acids in a
water and alcohol solution to form a mixture; (b) adding one
or more alkali salts to the mixture to form a salt solution;
(c) filtering the solution to separate un-reacted alkali salt
from a filtrate; and (d) recovering the soluble boswellic acid
mixture from the filtrate. Additionally, the new composition
can be formed by using super critical carbon dioxide. The new
composition can be used to alleviate numerous inflammatory
conditions, including, but not limited to, rheumatoid
arthritis and osteoarthritis, colon cancer, prostate cancer
and breast cancer, and a broad range of neurodegenerative
conditions, such as Alzheimer's disease and Parkinson's
disease. The composition can be administered parenterally,
orally, or topically.  
  
**BACKGROUND OF THE INVENTION :**   
[0003] Boswellia serrata is a large, branching, deciduous
tree, which grows abundantly in the dry, hilly parts of India.
The gum resin exudate of this tree, known in the vernacular
as"Salai guggal", has been used in the Ayurvedic system of
medicine for the management of arthritis, respiratory
diseases, and liver disorders.  
  
The major use of Boswellia serrata in modern medicine is as an
anti-arthritic and anti-inflammatory pharmacological agent.  
  
[0004] The active principles found in the gum resin,
specifically a combination of boswellic acids, have emerged as
effective non-steroidal anti-inflammatory compounds (NSAID's)
with broad biological activities and also a low ulcerogenic
index. Compared experimentally with the anti-inflammatory drug
phenylbutazone, boswellic acids did not produce injury to the
gastrointestinal mucosa. The most popular NSAID, aspirin,
although much better tolerated than its parent compound
salicylates, still has serious side effects, e. g.
gastrointestinal irritation and bleeding which limit its
long-term use. In addition, aspirin is contraindicated in
patients who have experienced asthma, urticaria (in general
allergic reactions), and should be administered with caution
in children and teenagers due to the risk of Reye syndrome.  
  
[00005] One way in which to explain how boswellic acids
function as NSAIDs in the treatment of inflammatory conditions
is to compare these natural compounds to aspirin without the
typical gastrointestinal irritation. Similar to aspirin,
boswellic acids inhibit the pathway leading from arachidonic
acid (a derivative of our body's phospholipids) to its
metabolic derivatives called leukotrienes and prostaglandins.  
  
An excess of leukotrienes and prostaglandins may be
responsible, directly or indirectly, for the classic signs of
inflammation ; redness (due to dilated vessels), swelling (due
to the blood vessels leaking out), pain (due to activation of
the pain receptors) and increased heat over the affected part
of the body. The specific biochemical mechanism of boswellic
acids differs from that of aspirin, however both compounds
result in the diminishment of the mediators of inflammation,
leukotrienes or prostaglandins, and the inflammation is
subdued.  
  
[0006] Studies designed to determine the anti-inflammatory
mechanism of boswellic acids indicate that their primary mode
of action involves the inhibition of 5lipoxygenase, the key
enzyme responsible in the formation of leukotrienes.  
  
Additionally, boswellic acids do not appear to impair the
peroxidation of arachidonic acid by iron and ascorbate. These
results suggest that boswellic acids are safe, specific,
non-redox inhibitors of leukotriene synthesis that operate
through a well defined mechanism.  
  
[0007] One of the most interesting properties of boswellic
acids is their anticomplementary activity. In in vitro
experiments boswellic acids prevented a wellknown
inflammatory"chain-reaction"involving several protein
compounds collectively known as"complement". This is due to
the inhibition of an enzyme that activates one of the
components of complement, C3 convertase. The domino effect of
the complement in the course of rheumatoid arthritis (or a
similar chronic inflammatory process) leads to a subsequent
elevation of the enzymes (e. g. cathepsins, glucuronidase and
human leukocyte elastase (HLE)) causing excessive catabolism
(wasting) of the joint-forming glycoproteins and
glycosaminoglycans.  
  
This tissue destructive process leads to continuously
worsening joint disfigurement, pain, and limited mobility. As
a consequence of complement-mediated tissue destruction, there
is an increased release of markers (metabolites) of the
connective tissue, e. g. hydroxyproline, hexosamine and uronic
acid. Boswellic acids have been found to decrease the levels
of tissue destructive enzymes and also of the levels of
urinary hydroxyproline, hexosamine and uronic acid in the
acute and chronic phases of experimental arthritis.  
  
[0008] There are four major b-boswellic acids involved in the
inhibition of 5lipoxygenase and related anti-inflammatory
events. These are: b-Boswellic Acid (BBA), Acetyl-b-Boswellic
Acid (ABBA), 11-keto-b-Boswellic Acid (KBBA), Acetyl-11-
keto-b-Boswellic (AKBBA), listed here in the order of
increasing anti-inflammatory properties.  
  
[0009] Boswellic acids have been found to be effective in
alleviation of numerous inflammatory conditions, including,
rheumatoid arthritis and osteoarthritis.  
  
[0010] A standardized extract of boswellic acids (200 mg tid)
was evaluated in a four week double blind, cross-over trial in
30 patients suffering from rheumatoid arthritis. The mean
arthritic score (sum of symptoms) and the biochemical index of
inflammation in the group receiving boswellic acids came down
significantly after the treatment. However, when the placebo
was substituted (crossover), the subjective and objective
indices of arthritis rose again. (See Majeed, M, Badmaev, V,
Gopinathan, S, Rajendran, R, Norton, T. Boswellin The
Anti-inflammatory Phytonutrient. Nutriscience Publishers, Inc.
Piscataway, N. J. 1996. pp. 78.) [0011] In another 20 patient,
double blind, crossover study a boswellia gum resin extract
(200 mg tid) combined in an herbomineral formula was evaluated
in the treatment of rheumatoid arthritis and separately in
osteoarthritis. Active and placebo treatments were given for a
period of three months. After a washout period of two weeks,
the regimens were crossed-over. The three month active therapy
resulted in a significant decrease in severity of pain,
morning stiffness, improved joint mobility score, grip
strength score and the overall disability score compared to
the placebo group. The biochemical index of inflammation was
also significantly improved due to the treatment. (See
Kulkarni, RR, Patki, PS, Jog, VP, Patwardhan, G & B.
Efficacy Of An Ayurvedic Formulation In Rheumatoid Arthritis:
A Double-Blind, Placebo Controlled, Cross-Over Study. Ind J
Pharmacol. 1992 ; 24: 98-101.) [0012] Ulcerative colitis is an
example of a chronic inflammatory process in the bowel, which
may be caused and/or aggravated by excessive leukotriene
production.  
  
Effects of Boswellia serrata gum resin (350 mg thrice daily
for 6 weeks) vs. the NSAID sulfasalazine was studied in
patients with ulcerative colitis. The tested parameters,
including stool properties, istolopathology of rectal
biopsies, and blood biochemistry improved after treatment with
the gum resin. As a result of the treatment, 82% of patients
went into remission, as compared to a 75% remission rate
obtained with sulfasalazine. (See Gupta, 1, Parihar, A,
Malhotra, P, Singh, GB, Ludtke, R, Safayhi, H, Ammon, HP.
Effects of Boswellia serrata gum resin in patients with
ulcerative colitis. Eur J Med Res. 1997 Jan; 2 (1) : 37-43.)
[0013] Boswellic acids were also tested in the management of
asthma, since a new generation of anti-asthmatic drugs is
based on the premise of being leukotriene inhibitors. In a
double blind, placebo-controlled study 40 patients with a
several years'history of bronchial asthma were treated with
300 mg tid of boswellia gum resin for a period of six weeks.
Seventy percent of the patients responded to the treatment as
evidenced by a reduction in dyspnea, ronchi, and number of
attacks, improvement in lung tests and blood biochemistry.
Only 27% of the patients receiving placebo showed clinical
improvement. (See Gupta, 1, Gupta, V, Parihar, A, Gupta, S,
Ludtke, R, Safayhi, H, Ammon, HP. Effects Of Boswellia Serrata
Gum Resin In Patients With Bronchial Asthma: Results Of A
Double-Blind, Placebo Controlled, 6-Week Clinical Study. Eur J
Med Res. 1998; 3: 511-514.) [0014] Finally, boswellic acids
also have use in the veterinary field. Several veterinarians
found success using boswellic acids in the treatment of
chronic inflammatory conditions in horses such as stifle
problems, sore backs, bowed tendons and bone spurs. In
addition, a preliminary study of boswellic acids in aging pet
dogs and cats showed beneficial effects in alleviating
arthritic conditions. (See Majeed, M, Badmaev, V, Gopinathan,
S, Rajendran, R, Norton, T. Boswellin The  
Anti-inflammatory Phytonutrient. Nutriscience Publishers, Inc.
Piscataway, N. J. 1996. pp. 78.) [0015] Sabinsa Corporation
manufactures different grades of Boswellic acids known under
the trademark Boswellin@, two of these are Boswellin
(standardized for 25% boswellic acids) and Boswellin Forte
(standardized for 40% boswellic acids).  
  
More specifically, the minimum amount of each boswellic acid
that must be present in these grades is:  
Boswellin Forte Boswellin BBA min. 11.0% 6.0% ABBA min. 8.0%
4.0% KBBA min. 7.0% 3.0% AKBBA min. 4.0% 1.5% [0016] Please
note that, of course, every acid may not be present in its
minimum amount as the required total percentages of boswellic
acids (40% and 25%) would not be met if this occurred.  
  
[0017] Such non-water soluble mixtures of BBA, ABBA, KBBA, and
AKBBA boswellic acids can be used as a pharmaceutical. Since
the ancient times, frankincense has been used in the
preparation of cosmetics and perfumes, and also as a fixative
in perfumes, soaps, creams, lotions and detergents.
Frankincense is a common name for Boswellia gum resin, and
Boswellia gum resin is a raw source from which boswellic acids
are extracted. The stabilizing effect of frankincense in
cosmetic preparations is directly related to the biological
properties of boswellic acids. The anti-inflammatory
properties of boswellic acids can also yield an interesting
applications for topical and cosmetic use of the extract of
Boswellia serrata. Boswellia cream for the management of
inflammatory conditions has been available for several years
in the US market. Its therapeutic composition includes,
roughly 5 wt. % boswellic acids, 0.025 wt. % capsaicin, an
extract of Capsicum annum fruits, and 10 wt. % methyl
salicylate.  
  
[0018] However, a problem associated with these formulations
is that they are not soluble in water. Therefore, there is a
great need in the field for water soluble boswellic acid
mixtures and salts.  
  
**SUMMARY OF THE INVENTION :**   
[0019] The new water-soluble composition can be formed through
a method comprising the steps of: (a) dissolving mixtures of
boswellic acids in a water and alcohol solution to form a
mixture; (b) adding one or more alkali salts to the mixture to
form a salt solution; (c) filtering the solution to separate
un-reacted alkali salt from a filtrate; and (d) recovering the
soluble boswellic acid mixture from the filtrate.  
  
[0020] Additionally, the new composition can be formed by
using super critical carbon dioxide. The new composition can
be used to alleviate numerous inflammatory conditions,
including, but not limited to, rheumatoid arthritis and
osteoarthritis, colon cancer, prostate cancer and breast
cancer, and a broad range of neurodegenerative conditions,
such as Alzheimer's disease and Parkinson's disease. It can
also be used in the prevention and treatment of cardiovascular
conditions such as stroke, coronary artery disease or
thrombophlebitis. The composition can be administered
parenterally, orally, or topically.  
  
**DETAILED DISCLOSURE :**   
[0021] As stated above, the composition can be formed by (a)
dissolving mixtures of boswellic acids in a water and alcohol
solution to form a mixture, (b) adding one or more alkali
salts to the mixture to form a salt solution, (c) filtering
the salt solution to separate un-reacted alkali salt from a
filtrate, and (d) recovering the soluble boswellic acid
mixture from the filtrate.  
  
[0022] Preferably, though, the method involves (a) dissolving
boswellin forte in a water and 5% methanol solution to form a
mixture, (b) adding one or more potassium salts to the mixture
to form a salt solution and then stirring the salt solution at
room temperature, (c) filtering the solution with a nutsche
filter to separate un-reacted potassium salts from a filtrate,
(d) recovering the soluble boswellic acid mixture from the
filtrate, (e) drying the filtrate with a vacuum drier at a
temperature of no more than 50 C, and (f) powdering the
filtrate.  
  
[0023] More preferably, the filtrate can be dried through
concentrating the filtrate free of the solvent to obtain a
solid, wherein this step also further comprises dissolving the
obtained solid in water to obtain a secondary mixture,
charcoalizing the secondary mixture, filtering the
charcoalized secondary mixture and spray-drying the resulting
product.  
  
[0024] Additionally, it is also possible to use the super
critical carbon dioxide method of obtaining the boswellic acid
mixture. Such a process would comprise the steps of (a)
dissolving a mixture of boswellic acids, preferably boswellin
forte, in a water and alcohol solution to form a mixture, (b)
adding one or more alkali salts to the mixture to form a salt
solution, (c) treating the salt solution with supercritical
carbon dioxide, (d) allowing the supercritical carbon dioxide
to evaporate to leave an oleoresin, (e) passing an alcohol
solution of the oleoresin through a column packed with an
anion exchange resin, and (f) collecting the soluble boswellic
acid mixture from the eluent. Furthermore, it is preferred
that the treatment of the salt solution take place for at
least 10 hours and that the alcohol solution be 5% methanol
and 95% water. Suitable resins include Amberjet 4200 (cl),
Amberlite IRA 410, Amberlite IRA 900, Dowex 1x2-100, Dowex
22cl, Dowex Marathon A2, Dowex MSA 1, Dowex 550 A, all of
which are Rohm-Haas or Dow products. The oleoresin is
preferably passed through the resin at a rate of 20-50 L per
hour.  
  
[0025] The processes described above produce a water soluble
composition, preferably comprising at least 12.5% by weight of
the alkali salt of BBA, at least 9.57% by weight of the alkali
salt of ABBA, at least 8.15% by weight of the alkali salt of
KBBA, and at least 3.72% by weight of the alkali salt of
AKBBA, the remainder of the water soluble composition being
organic acids or matter, and the alkali salts thereof. This
composition of boswellic acids is suitable for the treatment
of many inflammatory conditions including rheumatoid arthritis
and osteoarthritis, colon cancer, prostate cancer and breast
cancer, and a broad range of neurodegenerative conditions,
such as Alzheimer's disease and Parkinson's disease. It can
also be used in the prevention and treatment of cardiovascular
conditions such as stroke, coronary artery disease or
thrombophlebitis.  
  
[0026] The composition may be administered to the subject
orally, parenterally, or topically. For preparing
pharmaceutical compositions containing compounds of the
invention, inert, pharmaceutical acceptable carriers are used.
The pharmaceutical carrier can be either solid or liquid.
Solid form preparations include, for example, powders,
tablets, dispersible granules, capsules, creams, and cachets.  
  
[0027] A solid carrier can be one or more substances which can
also act as diluents, flavoring agents, solubilizers,
lubricants, suspending agents, binders, or tablet
disintegrating agents; it can also be an encapsulating
material. In powders, the carrier is generally a finely
divided solid which is in a mixture with the finely divided
active component. In tablets, the active compound is mixed
with the carrier having the necessary binding properties in
suitable proportions and compacted in the shape and size
desired.  
  
[0028] Powders and tablets preferably contain between about 5%
to about 70% by weight of the active ingredient. Suitable
carriers include, for example, magnesium carbonate, magnesium
stearate, talc, lactose, sugar, pectin, dextrin, starch,
tragacanth, methyl cellulose, sodium carboxymethyl cellulose,
a low-melting wax, cocoa butter and the like. The
pharmaceutical compositions can include the formulation of the
active compound with encapsulating material as a carrier
providing a capsule in which the active component (with or
without other carriers) is surrounded by a carrier, which is
thus in association with it. In a similar manner, cachets are
also included. Tablets, powders, cachets, and capsules can be
used as solid dosage forms suitable for oral administration.  
  
[0029] Liquid pharmaceutical compositions include, for
example, solutions suitable for oral or parenteral
administration, or suspensions, and emulsions suitable for
oral administration. Sterile water solutions of the active
component or sterile solutions of the active component in
solvents comprising water, ethanol, or propylene glycol are
examples of liquid compositions suitable for parenteral
administration.  
  
[0030] Sterile solutions can be prepared by dissolving the
active component in the desired solvent system, and then
passing the resulting solution through a membrane filter to
sterilize it or, alternatively, by dissolving the sterile
compound in a previously sterilized solvent under sterile
conditions.  
  
[0031] Aqueous solutions for oral administration can be
prepared by dissolving the active compound in water or other
appropriate solvents and adding suitable flavorants, coloring
agents, stabilizers, and thickening agents as desired. Aqueous
suspensions for oral use can be made by dispersing the finely
divided active component in water together with a viscous
material such as natural or synthetic gums, resins, methyl
cellulose, sodium carboxymethyl cellulose, and other
suspending agents known to the pharmaceutical formulation art.
Preferably, the pharmaceutical composition is in unit dosage
form. In such form, the composition is divided into unit doses
containing appropriate quantities of the boswellic acid
mixtures. The unit dosage form can be a-packaged preparation,
the package containing discrete quantities of the preparation,
for example, packeted tablets, capsules, and powders in vials
or ampules. The unit dosage form can also be a capsule,
cachet, or tablet itself, or it can be the appropriate number
of any of these packaged forms.  
  
[0032] The specific dosages employed, however, can be varied
depending upon the requirements of the patient, and the
severity of the condition being treated. The preferred dosage
of the alkali boswellic acid salts given is 50-800 mg per day.
More preferably, the dosage is 100-600 mg per day. Even more
preferred is a dosage of 150-300 mg per day. Most preferred is
a dosage of about 200 mg per day, which is preferably
administered by doses of 200 mg of the boswellic acid salt
composition 3 times a day. The determination of optimum
dosages for a particular situation is within the skill of the
art.  
  
**BRIEF DESCRIPTION OF DRAWINGS :**   
[0033] Figure 1: This diagram reflects the boswellic acid
composition of the Potassium Boswellin used in Example 1 and
the composition of the Boswellin forte used to create the
Potassium Boswellin used in Example 1.  
  
[0034] Figure 2: This diagram reflects the presence of the
four boswellic acids in the serum of Individual A at
5,10,20,40,80, and 160 minutes.  
  
[0035] Figure 3: This diagram reflects the presence of the
four boswellic acids in the serum of Individual B at
5,10,20,40,80, and 160 minutes [0036] Figure 4: This diagram
is a graph charting the serum levels of the various four
boswellic acids in the serum of Individual A at the
5,10,20,40,80, and 160 minute intervals.  
  
[0037] Figure 5: This diagram is a graph charting the serum
levels of the various four boswellic acids in the serum of
Individual B at the 5,10,20,40,80, and 160 minute intervals  
  
**EXAMPLES****Example 1:**  
An initial batch of 1 kg Potassium Boswellin was prepared
using 40% Boswellin Forte material (see Figure 1).  
  
Potassium Boswellin and Boswellin 40% were then orally
administered to two human volunteers who had spent the
previous 16 hours fasting. 1 gram of Potassium Boswellin was
given to Individual A and 1 gram of Boswellin 40% was given to
Individual B. Both the Potassium Boswellin and the Boswellin
40% were suspended in 35 mi of milk and given to the subjects
to consume. 5 ml of blood was withdrawn from the volunteers at
intervals of 5,10,20,40,80, and 160 minutes.  
  
The blood samples were collected into sterile centrifuge tubes
and left for 120 minutes to retract the clot. The samples were
then centrifuged to separate the serum. The serum was
transferred to sterile 2 mi vials and stored at 0 C-4 C
overnight.  
  
The serum samples were then brought to room temperature. 1 ml
of the serum was placed into a 10 ml stoppered volumetric
flask and 1 ml of 3 N HCI was added to it. This mixture was
then sonicated for 20 minutes to free the boswellic acid. The
volume of the mixture was then brought to 10 ml with methanol
and the resulting solution was sonicated for 10 minutes to
extract the boswellic acids and to precipitate the serum
proteins. This prepared sample was then transferred into
capped centrifuge tubes and centrifuged at 4,000 rpm for 10
minutes. The serum proteins were precipitated as sediment and
the clear supernatant was filtered through No. 1 filter paper.  
  
The clear supernatants were then subjected to a HPLC assay,
the results of which are shown in Figures 2-5. As can be
plainly seen, the serum with Potassium Boswellin shows that a
greater amount of boswellic acids have been absorbed by the
subject's bloodstream, thereby demonstrating the efficacy of
the present invention.  
  


---

  

**EXTRACT OF OLIBANUM (FRANKINCENSE GUM)
IN THE FORM OF NANOPARTICLES, AND USE THEREOF**  
**WO2006128634**

  
[ Machine translation ]  
  
The invention relates to a novel and improved nanoparticulate
form of a frankincense gum extract, containing, inter alia,
Boswellic acids and/or their derivatives. The nanoparticles
have advantageous properties for use in the treatment of
inflammatory diseases. Surprisingly, these advantages are
obtained both in topical application and oral administration.
When used in topical formulations, the nanoparticles are
better absorbed by the skin than are known, tacky extracts,
and they are thus suitable for the treatment, for example, of
neurodermatitis and/or actinic keratosis and/or basal cell
carcinoma and/or epithlioma and/or squamous cell carcinoma of
the skin. For example, in soft gel capsules that dissolve in
the small intestine, the nanoparticles have much improved
bioavailability, which also considerably improves oral
administration for treatment of inflammatory conditions.
Finally, the nanoparticles can also be used for coating stents
and implants.  
  
0001] extract from olibanum (incense) in the form of
nanoparticles and  
  
[0002] using the same  
  
[0003] The invention relates to a new and improved
nanoparticulate form of a Olibanumextraktes (incense extract)
containing, among other boswellic acids and / or derivatives
thereof.  
  
The dissolved Olibanumextrakt embedded in spherical particles
having a three-dimensional size in the nanometer (nm) range.  
  
The so-called nanoparticles have advantageous properties in
terms of a use for treating inflammatory diseases.  
Surprisingly these advantages are obtained both for a topical,
an oral administration as well as a surface coating of
implants.  
  
The nanoparticles are absorbed better when used in topical
formulations of the skin known as sticky extracts and thus
suitable for the treatment of, for example, atopic dermatitis
and / or actinic keratosis and / or basal cell carcinoma and /
or squamous and / or squamous cell carcinoma of the skin.  
  
For example, in enteric softgels show the olibanum
nanoparticles significantly improved bioavailability, which
also improves oral use in the treatment of inflammatory
conditions significantly.  
  
Finally, Olibanum nanoparticles can also be used for coating
of implants (vessel joint, bone, tooth) and surgical sutures.  
  
[0004] state of the art early in oriental folk medicine is the
use of incense, primarily in India and in the Near East, for
the treatment of various diseases, especially inflammation and
rheumatic joint diseases known.  
Even in recent times several medical applications have been
found for incense or Olibanumextrakte and especially for
boswellic acids and their derivatives.  
  
Inflammatory responses are measures of the organism, which
serve to remove the damaging tissue damages by causing foreign
bodies or the damaged part of the tissue repair and replace
tissue.  
  
Hence, inflammation is a physiological process.  
  
However, there are a number of situations in which functions
of organs are disturbed by inflammatory processes, especially
when they are shooting or chronic.  
  
Inflammation is triggered by the release of so-called
biochemical mediators of inflammation.  
  
There are two types of different inflammatory mediators that
are involved in the formation and maintaining inflammatory
prostaglandins and leukotrienes.  
  
The current therapy of inflammation occurs with drugs that are
predominantly in a position called the arachidonic acid
cascade, namely to block the part of the leads to the
formation of Prostaglandiene.  
  
The drugs used are among the steroidal and non-steroidal
anti-inflammatory drugs.  
  
The anti-inflammatory effects of these drugs is associated
with significant side effects.  
  
[0005] The anti-inflammatory effect of boswellic acids has
been repeatedly published (Safayhi, H., et.  
AI, Planta Medica 63, 487-493, 1997. J. Pharmacol. And Exp
Ther, 261, 1143-46, 1992). Sashwati et al investigated by
screening the human genome, the genetic basis of the
anti-inflammatory effect of Boswellia in microvascular
endothelial cells and found an inhibition of 5 -lipoxygenase,
a key enzyme in the biosynthesis of leukotrienes. The research
revealed that 3-O-acetyl-11-keto-boswellic acid is the most
potent as 5-lipoxygenase inhibitor among the boswellic acids.  
  
In addition, the boswellic acids prevented the
TNF-alpha-induced expression of metalloproteinases and of
mediators of apoptosis.  
  
It was also the expression of  VCAM-1 and ICAM-1
suppresses Olibanumextrakte.  
  
This research showed that Olibanumextrakt by influencing the
mechanisms of inflammation Signalmecha anti-inflammatory
effect (Sashwati, R., et al, DNA AND CELL BIOLOGY:. VoI 24,
Number 4, 2005).  
  
[0010] EP 552 657 A1 discloses that pure boswellic acid, the
physiologically compatible salts borrowed, derivatives thereof
and salts of derivatives or a herbal preparation containing
boswellic acid can fight inflammation, caused by increased
leukotriene formation.  
  
It is suggested in the treatment of inflammatory joint
diseases, epidermal lesions, allergic and chronic asthma,
Endoxinschock, inflammatory bowel disease and chronic
hepatitis with these compounds.  
  
[0011] WO 90/01937 reports that a-and ss-Boswelliaacetat
Boswelliaacetat and its analogs inhibit topoisomerase I and
topoisomerase II.  
  
Therefore, this document proposes to use the compounds for the
treatment of various cancers.  
  
[0012] WO 97/07796 uses boswellic acid, a physiologically
acceptable salt, derivative, a salt of said derivative or a
boswellic acid-containing herbal preparation for the
prophylaxis and / or the control of diseases that are caused
by increased Leukozytenelastaseoder PiasminaktivitAcurrencyt.  
  
Therefore, this document proposes to use the compounds in the
treatment of diseases such as emphysema, acute respiratory
distress syndrome, adult respiratory distress syndrome, cystic
fibrosis, chronic bronchitis, glomerulonephritis and
rheumatoid arthritis, and also to inhibit the growth and
metastasis of many cancers.  
  
[0013] WO 02/15916 discloses DihydroboswelliasAcurrencyuren,
physiologically acceptable salts thereof, and hydrogenated
extracts of boswellia.  
  
It is proposed to use these compounds for prophylactic and /
or therapeutic treatment of adverse physical and psychological
conditions, especially of somatic, psychosomatic and mental
disorders such as inflammatory processes, which are caused by
increased leukotriene formation, Leukozytenelastaseoder
PiasminaktivitAcurrencyt.  
The above diseases are, for example inflammatory joint
diseases, epidermal lesions, allergic and chronic asthma,
endotoxin, inflammatory bowel disease, chronic hepatitis,
pulmonary emphysema, acute respiratory distress syndrome,
shock lung, cystic fibrosis, chronic bronchitis,
glomerulonephritis and rheumatoid arthritis as well as
specific tumors and tumor metastases.  
  
[0015] DE 101 21 252 A1 describes the treatment of acne, a
hormone-induced inflammatory skin disease, the use of
lipoxygenase inhibitors alone or in combination with other
lipoxygenase inhibitors or with other anti-acne agents in a
suitable pharmaceutical composition, in particular by oral and
/ or locally-applied topically.  
  
[0016] In the publication U.S. 2004/0166178 A1 discloses the
use of 3-O-acetyl-11-keto-boswellic acid is described in a
formulation for topical application for relaxation of the skin
and for the treatment of facial wrinkles.  
  
[0017] In summary it can be said that incense and
Olibanumextrakte is known as a traditional natural remedies or
medicines to treat various physical and mental conditions.  
  
Because of the versatility of the applicability of the good
effect coupled with reduced side effects, there is a great
need to provide Olibanumextrakte in an improved form, and this
improved formulation for as many applications, such as topical
and oral administration as well as for coating implants and
should be suitable for surgical sutures.  
To skin diseases  
  
[0018] In the case of eczema (including atopic dermatitis,
eczema atopic, eczema diffusa, eczema disseminated, eczema
constitutionalis, endogenous eczema Besnier-prurigo) is a
chronic or chronically relapsing, in their morphological
aspect and overall process quite different types of
inflammatory skin disease which is accompanied by severe
itching.  
  
The eczema is hereditary and often occurs together with other
atopic diseases such as allergic rhinitis, allergic
conjunctivitis and allergic bronchial asthma on.  
  
Biochemically is neurodermatitis a fault in the humoral and
cellular immunity, the infection is associated with a high
activity of the skin.  
  
The current treatment of these inflammatory skin disorder is
often performed by means of the external application of
glucocorticoids in the form of ointments or creams.  
  
This inflammatory activity is indeed reduced, but the
treatment is associated with significant side effects with
cortisone.  
  
[0019] The incidence of "light skin cancer," meaning
Kanzerosen as actinic keratoses, basal cell carcinomas,
squamous cell carcinomas and squamous fall, takes explosively
in the temperate latitudes.  
  
The "light skin cancer" is ten times more common than
melanoma, the skin cancer known as black. Every seven years,
double the number of cases. One of the causes is sun exposure
and skin damage caused by UV radiation and the frequent use of
tanning beds.  
  
The actinic keratoses are now no longer classified as a
precancerous condition, but as an early cancer.  
Approximately every second German has over 60 years due to
many years of UV light exposure to actinic keratoses.  
  
Most actinic keratoses persist as long Carinoma in situ,
whereas 20% show spontaneous remission or develop into
invasive carcinomas spinozellAcurrencyre.  
  
There are now following therapeutic options: 1 Surgical
removal (eg As excision, curettage, cryosurgery), with mostly
100% remissions are obtained. However, there remain scars and
surrounding skin areas that were indeed exposed to the same UV
exposure, remain untreated.  
  
 2 Chemotherapies (eg As 5-fluorouracil or podophyllin)
reach up to 85% remissions and can be applied areally.  
However, they must be carried out over weeks, are painful and
can leave scars and pigmentation.  
  
[0021] 3 Photodynamic Therapy: After photosensitization by 5 -
aminolevulinic acid cream light to destroy the tumor cells.
Remissions and good cosmetic results can be achieved. For
this, the procedure is painful phototoxic reactions are
possible.  
  
[0022] 4 Immunomodulators: For example, with imiquimod or
diclofenac as a cream or gel remissions in up to 80% of cases
can be achieved and the actinic keratoses can be removed
without leaving any scars. The treatment is repeated, but it
takes at least 12 weeks and requires a high level of patient
compliance.  
  
[0023] In the above-mentioned skin diseases is a high
inflammatory activity with activation of inflammatory
mediators, such as prostaglandins and the 5-lipoxygenase. In
the skin lesions can be as in the basal cell carcinoma,
squamous and squamous skin cells degenerate prove. By
antiphlogistic drugs that interfere with the prostaglandin,
such as diclofenac, remission can be achieved, but these drugs
are known side effects.  
  
Boswellic acids that occur from Olibanumharz in the extract
have anti-inflammatory, antiproliferative and cytostatic
effects.  
  
The anti-inflammatory action based on inhibition of
5-lipoxygenase, in an essential enzyme for the synthesis of
leukotrienes (see, for B. Safayhi et al., Mol Pharm 47,
1212-1216, 1995. Sailer et al, Arch Pharm 329, 54-56, 1996)
and the inhibition of leukocyte elastase, as described in EP
854 709th  
  
Furthermore, boswellic acids have a cytostatic effect.  
  
It is reported more recently, of chemopreventive and
therapeutic effects of acetyl-keto-boswellic acids in the
treatment of various cancers.  
  
This seems to be the inhibition of topoisomerase-1, alpha
TopoisomeraseIl and induction of apoptosis through activation
of caspase-3 and -8 play a key role by boswellic acids
(Jian-Jun Liu, et. AI., Intern. J. of Molecular Medicine 10:.
501-505, 2002, Shao et al, Planta Medica 64, 328-331, 1998).
These effects appear to be suitable as boswellic acids for
treatment of tumors, as described in EP 871 437  
  
[0024] Treatment of inflammatory and malignant skin diseases
Olibanumextrakten and / or boswellic acids and derivatives
thereof is generally known in the prior art. However, arises
with the topical use of the extracts, the problem that they
are typically sticky and thus have the property not to be
absorbed by the skin and therefore can not operate in the
deeper skin layers.  
  
[0025] There is therefore a need, extracts of frankincense in
a form more available for topical applications to provide that
optimally penetrate into the skin to the skin in order to be
pharmacologically active either topically or systemically.  
  
 **Vascular disease**  
[0026] Atherosclerosis is the cause of heart attacks, strokes
and peripheral vascular occlusive disease of the extremities
and is a chronic inflammatory fibroproliferative disease of
the arterial wall, which is associated with an impaired immune
response.  
  
Inflammatory processes, the inner wall of arteries, the
intima, disturbed in their integrity and particularly loaded
vessel sections, for example on vessel bifurcations occur
injuries and lacerations of the intima.  
Inflammatory cells in the lesions themselves are deposited as
monocytes, macrophages, dendritic cells, mast cells and
neutrophils.  
Mast cells are transformed by taking up oxidized low-density
lipoproteins (LDL) in foam cells and to form the "lipid core"
of the so-called plaques, inflammatory ulcers in the vessel
wall.  
Reduce by chronic inflammation with activation of
metalloproteinases, enzymes, connective tissue and collagen,
the connective tissue sheath layer of the plaques is injured
and the lipid-containing core of the plaques come in contact
with the coagulation system of the blood, it forms very
quickly Gerinnungspfropf which closes the vessel .  
This process occurs in a coronary artery that supplied by the
vascular portion of the heart muscle dies from lack of oxygen.
A heart attack is the result. Atherosclerotic processes in the
brain that trigger strokes.  
  
[0027] The inflammation of the vessel wall are activated by
inflammatory mediators, such as prostaglandins and
leukotrienes released. Leukotrienes are formed via the
5-lipoxygenase cascade of inflammation. It has been shown that
5-lipoxygenase expressed in increasing concentrations at
various stages of atherosclerosis in the arterial wall
(Spanbroek, R.; PNAS, Vol 100, No. 3, 1238-1243, 2003). The
authors proposed a new model of atherosclerosis in which
mediated by the 5-lipoxygenase inflammatory activity in the
vessel wall is the cause of the progression of atherosclerotic
lesions.  
  
[0028] Inflammatory markers in the blood of patients with
atherosclerosis have elevated levels of C-reactive protein,
interleukin 116, tumor necrosis factor alpha (TNF-alpha), a
reduced antioxidant capacity, increased lipid peroxidation and
increased homocysteine ??concentrations.  
In the treatment of patients with coronary heart disease with
statins, that lipid-lowering drugs, in addition to a reduction
of the anti-inflammatory effects LDLCholesterinspiegels a
reduction was observed with the C-reactive protein
concentration.  
This effect was accompanied by a significant reduction in the
risk of sudden cardiac death and stroke and the significant
decrease in the lipid core forming lipoproteins (LDL) and
inflammatory activity has been attributed.  
  
[0029] The treatment of atherosclerosis, coronary heart
disease is classically with medications such as statins,
beta-blockers, ACE inhibitors, and acetylsalicylic acid, which
all require considerable side effects.  
  
[0030] Olibanumextrakte point, as explained in detail above,
anti-inflammatory and antiproliferative effects on cytostatic,
which is also known from the prior art.  
These effects make the extracts useful in the treatment of
inflammatory processes and vascular proliferative diseases,
arteriosclerosis, and side effects of conventional drugs can
be avoided.  
  
[0031] However, there is a need, extracts of frankincense in a
more bioavailable form for oral administration to provide.
implants  
  
[0032] As an example, stents: percutaneous transluminal
angioplasty (PTA) of blood vessels, especially the coronary
artery angioplasty (PTCA) is a very common way to eliminate
strictures or stenoses, which obstruct the blood supply of
human organs.  
  
Endovascular stents are used as a scaffold in order to prevent
a sudden arterial occlusion in the angioplasty.  
Stents may also reduce the restenosis rates as compared with a
conventional balloon angioplasty.  
  
Restenosis after stent implantation, however, provide at rates
20-30% remains a Problern in coronary arteries dar.  
Restenosis is the result of massive blood vessel damage with
induction of inflammation and endothelial cell proliferation
stimuli for the use of a stent.  
  
Rates of restenosis following stent implantation are also from
the stent design and material dependent.  
From WO 90/13332 and WO 91/12779 stent has become known, which
are coated with anti-inflammatory drugs gerinnungsund to
reduce restenosis rates.  
  
The erfolgversprechensten drugs that may reduce restenosis
rates effective agents include rapamycin (sirolimus (R)) and
paclitacel (Taxol (R)).  
  
[0033] Rapamycin is a macrolide antibiotic which has both
anti-inflammatory and antiproliferative properties.  
It prevents smooth muscle cell proliferation and reduces the
inflammatory response induced by stent implantation by
inhibition of proinflammatory cytokines (Suzuki et al.,
Circulation 104 (10), 1188-1193, 2001).  
  
[0034] One of the disadvantages of the currently discussed
eluting stents is the delayed epithelialization of the stent
inner surface, so that the antithrombotic therapy to prevent
must be in-stent thrombosis significantly prolonged time.
There is thus a need to provide an alternative means which is
suitable to coat stents.  
  
[0035] The object of the invention is therefore to provide
Olibanumextrakt in a form which can be used in pharmaceutical
and / or cosmetic and / or for the coating of the implant
surface, and thereby improves the corresponding means.  
  
This improvement should be guaranteed for different
application forms such as topical and oral administration.  
In the area of ??topical application is to be achieved in that
the or can be absorbed by the skin, the active compounds of
the Olibanumextrakts better.  
  
In the oral administration of Olibanumextrakt the active
ingredient to be more bioavailable.  
  
In the application for the coating of surfaces of implant
treatment of vascular disease is to be provided for example by
means of a stent in the form Olibanumextrakt within which
makes the coating of the stent with the active compound or
compounds of Olibanumextrakt possible.  
  
[0036] These objects are achieved by the subject matter of the
claims.  
  
[0037] Surprisingly it was found that Olibanumextrakte in
nanoparticulate form are perfectly suitable, on the one hand
in formulations for topical administration and the other in
formulations for oral administration significantly improve
their properties.  
  
When applied topically, the active ingredient (or active
ingredients) is much better absorbed by the skin than is the
case with the use of conventional extracts.  
  
For oral administration, preferably in enteric soft gel
capsules, the bioavailability of the active substance (or
substances) is considerably improved.  
  
It was also found that Olibanumextrakte in nanoparticulate
form are an excellent way to coat implants such as stents or
other (port system, joint prostheses, Herzschrittmaeher,
dental pins, screws, plates, Kirschner wires).  
  
Also has been found out that surgical sutures (eg As
polyethylene), and indwelling indwelling, vascular catheters
can be coated with Olibanumextrakt-Nanopartikenl.  
  
The devices mentioned can cause foreign body reactions in the
human body, which may be associated with inflammation and even
with Granulombildungen.  
  
Surprisingly, it has been found that the coating of the device
with OlibanumNanopartikeln prevent foreign body reaction or
can be counteracted.  
  
Ultimately, it has proved advantageous to add as additive to
Olibanumextrakt storage solutions for biological materials in
nanoparticulate form.  
  
These can be used in transport solutions for organs, as used
for example in organ transplantation.  
[0038] Olibanumextrakt can be obtained by, for example,
ethanol, methanol, ether or chloroform extraction extraction
of resin of olibanum. Preferably, such extracts are
lipophilic.  
  
[0039] According to a preferred embodiment of the invention
the Olibanumextrakt with acetyl-11-keto-boswellic acid is
enriched ss.  
  
Optionally, the hydrogenation of incense, and the
physiologically acceptable salts and derivatives, as well as
hydrogenated Olibanumextrakte can be used.  
  
Suitable [0040] According to the invention as an additive
containing boswellic acids are also herbal extracts, their
hydrogenation, boswellic acids, physiologically acceptable
salts of the boswellic acids, derivatives of boswellic acids,
herbal preparations containing boswellic acid or
acetyl-11-keto-boswellic acid ss-containing plant extracts.  
Also suitable are hydrogenation products of other ingredients
of the incense, such as from the other TirucallensAcurrencyure or
triterpenoid compounds, salts or derivatives thereof as well
as plant extracts containing these compounds.  
According to the invention are suitable as an additive
continue the hydrogenation of acetyl-11-keto-boswellic acid or
ss-ss-11-keto-boswellic acid or ss-boswellic acid, the latter
may contain small amounts of alpha or gammaBoswelliasAcurrencyure.  
  
Also suitable are hydrogenation of ss-boswellic acid,
BoswelliasAcurrencyureformiat ss, ss-boswellic acid,
acetyl-ss-boswellic acid, but also of the boswellic acids and
derivatives of boswellic acids, which are described in DE-A 42
01 903, of which reference is made to the will.  
  
[0041] boswellic acids, in particular acetyl-11-keto-boswellic
ss can, in a known manner to be obtained from boswellic
acid-containing plants.  
  
Suitable Boswelliaarten are: Boswellia serrata, Boswellia
carteri, Boswellia sacra, Boswellia papyrifera, Boswellia
frereana, boswellia or Boswellia thurifera glabra, but also
other members of the Boswellia family, or Commiphora family
can be used.  
  
[0042] As inventive hydrogenation can DihydroboswelliasAcurrencyuren,
their physiologically acceptable salts, derivatives thereof,
and physiological salts of derivatives, in particular
ss-dihydro-boswellic acid acetate, ss DihydroboswelliasAcurrencyure
formate, ss DihydroboswelliasAcurrencyure methyl ester,
acetyl-ss-dihydroboswelliasAcurrencyure, alpha dihydro-boswellic acid,
acetyl-a-formyl-a-dihydroboswelliasAcurrencyure and
dihydroboswelliasAcurrencyure be used.  
  
[0043] According to the invention are also suitable keto
DihydroboswelliasAcurrencyuren their physiologically acceptable salts,
derivatives thereof and physiological salts of the
derivatives, especially
acetyl-11-keto-ss-dihydroboswelliasAcurrencyure,
11-keto-ss-dihydroboswelliasAcurrencyure or formyl-11-keto-ss
-dihydroboswelliasAcurrencyure.  
The compounds useful according to the invention can be
obtained by hydrogenation, preferably by catalytic
hydrogenation.  
  
The hydrogenation of these compounds is carried out in a
manner known in the art, preferably so that the backbone of
the compound is selectively hydrogenated.  
  
Such a method is described for example in WO 02 / 15916th  
  
[0044] For the preparation of the inventive pharmaceutical
composition may further contain a hydrated plant extract is
from incense, for example, ethanol, methanol, chloroform
extraction, ether extraction, or obtained may be used.  
  
[0045] The Olibanumextrakte used in the invention include, in
particular ss-boswellic acid and / or acetyl-ss-boswellic acid
and / or acetyl-11-keto-ss-boswellic acid and / or
11-keto-ss-boswellic acid and optionally with acetyl-11-
beta.-keto-boswellic acid at levels higher than the natural
content enriched.  
  
[0046] In accordance with the invention physiologically
acceptable salts, especially the sodium, potassium, ammonium,
magnesium and calcium salts of the above compounds are
understood.  
  
Derivatives such as in particular Ci-C6 - alkyl esters of
DihydroboswelliasAcurrencyure understood, in which the carboxyl group
of the DihydroboswelliasAcurrencyure was esterified with a
corresponding alcohol.  
  
Such DihydroboswelliasAcurrencyurealkylester are for example the
methyl ester, ethyl ester, n-propyl, iso-propyl, n-butyl,
iso-butyl esters and the tertButylester
DihydroboswelliasAcurrencyuren.  
  
It is also possible that the hydroxyl group of the
DihydroboswelliasAcurrencyure is esterified with a physiologically
acceptable carboxylic acid, for B. a dbis C2o, in particular
having a CRC8 carboxylic acid, in particular formic acid or
acetic acid.  
  
Herbal preparations that can be used for the preparation of
the novel Olibanumextrakte are commercially available, for
example from the company PL-Thomas, New Jersey under the name
5-Loxin (TM).  
This is a standardized Olibanumextrakt of Boswellia serrata,
at least 30% of the acetyl-11-keto-ss-boswellic acid contains.  
  
[0047] According to the invention, however, can also
Olibanumextrakte and their hydrogenation products are used by
other preparations, in particular according to the invention
can also hydrogenation synthetically manufactured or natural
way derived ingredients of incense, especially
acetyl-11-keto-ss-boswellic acid and / or 11 -
beta.-keto-boswellic acid and / or ss-boswellic acid,
optionally in admixture with a-und/oder yBoswelliasAcurrencyure and /
or several of the derivatives according to the invention are
preferably used the boswellic acid, as described above, to
produce the drug.  
  
[0048] According to the invention, the medicament in addition
to the herein defined, based on incense ingredients or other
active ingredients, especially other herbal ingredients
contained.  
  
[0049] According to the invention is brought into a
nanoparticulate form with one or more of the optional
additives described above, the Olibanumextrakt.  
  
Preferably, the nanoparticles have a size in the range of 30
to 400 nm, preferably 60 to 200 nm, more preferably from 100
to 200 nm.  
  
Those skilled in the art will vary depending on use of the
medicine anvisierter known per se and suitably produce
nanoparticles.  
  
[0050] Since the Olibanumextrakt, especially the hydrogenated
Olibanumextrakt and especially the hydrogenated boswellic
acids and their derivatives and salts have a very low
toxicity, their compatibility is generally good.  
Your dosage can be easily selected by the treating physician
according to the severity of the condition being treated and
other factors such as the duration of the disease, possible
known incompatibilities of the patient's general condition of
the patient, etc..  
  
The drug according to the invention can be formulated so that
it is in unit doses one or more times daily, in particular
mono-to four times a day can be administered.  
  
[0051] For topical application, the inventive nanoparticles
can be incorporated into dermatocosmetic ointment bases, which
can be applied several times daily to the affected skin.  
  
The inventive pharmaceutical compositions may be, for example,
in solid, semisolid, or liquid form.  
Suitable creams, ointments, gels, lotions, etc.  
  
[0052] For oral administration come into consideration
tablets, granules, capsules, solutions, etc., which include
pharmaceutically acceptable additives in addition to the
invention nanoparticles.  
  
Furthermore, the pharmaceutical compositions may be in a
manner known in the art as liquid compositions for oral
administration.  
  
Preference for oral administration enteric softgels are thin.  
  
[0053] The invention is not to be bound by the following
statement, but probably have the novel nanoparticles of the
active substance (or substances) in enteric softgels to a
significantly improved bioavailability, since the
nanoparticles probably similar transport mechanisms in the
intestine as the Phosphatidylcholinmatrix triglycerides are
absorbed via chylomicrons.  
  
Other examples of suitable formulations and methods for their
preparation can be found in DE-A 44 44 288 and DE-A 44 45 728,
to the extent fully incorporated herein by reference.  
  
[0054] Finally, the invention nanoparticles of the active
ingredient (or ingredients) for coating
medikamenteneluierenden implants, such as stents, are
suitable.  
  
By the inhibitory effect on the proliferation of smooth muscle
cells in the vessel wall and by inhibiting the inflammatory
processes counteract the novel nanoparticles of in-stent
restenosis.  
  
According to the international medical literature, it comes
with the conventional stent within the first six months in 30%
of cases a stent closure or to an in-stent stenosis.  
  
For nanoparticles coated with the inventive stent is a high
probability that this closure rate can be significantly
reduced.  
  
[0055] By inhibiting effect on the proliferation of connective
tissue cells, and by inhibiting the inflammatory processes as
an additive to implant erfindungsmAcurrencyssen OlibanumNanopartikel
Cement (bone cement) act against the surface of implants of
FremdkAPrpergranulombildung and loosening of joint implants by
EntzA1/4ndungsund against degeneration processes.  
  
[0056] Examples  
  
[0057] Example 1:  
  
[0058] Use of the nanoparticles according to the invention as
a topical cream to treat inflammatory skin diseases,  
  
[0059] 1-5% (relative to the ointment base) of the novel
nanoparticles are applied morning and evening to the affected
skin and gently massaged.  
  
Inflammation is a visible reduction in pilot studies in
actinic keratosis, eczema and psoriasis already detectable
after one week.  
  
For example, the inflammatory lesions were completely healed
after a treatment period of 6 weeks at a cohort of 5 patients
with actinic keratoses in 3 patients.  
  
In one patient the result was confirmed histologically.  
  
In 2 patients, the skin lesions were significantly improved.  
  
[0060] Example 2:  
  
[0061] possibility of enhancing the effect of  
  
[0062] In inflammatory skin diseases according to the
invention nanoparticles were prepared as described in Example
1 above, is applied. In addition, activation was:  
  
[0063] 1 A soft laser, 785 nm, laser shower (from MKW Laser
System) with 14 x 10 mW power, 5 minutes in direct skin
contact times per two weeks and  
  
[0064] 2 With water-filtered infrared-A (from Hydrosun) for 20
min at 30 cm distance, two per week, performed once. The
infrared activation of nanoparticles according to the
invention was carried out 2 times a week.  
By activation with infrared led to a much faster effect.  
  
The postulated mechanism could be a direct activation of
boswellia triterpenes by energy absorption and improve the
penetration properties of the skin by a low-thermal radiation.  
  


---

  

**Optimized frankincense and myrrh
treating process**  
**CN1349813**

  
[ Machine translation ]  
  
The optimization treatment process of the Chinese medicinal
materials of frankincense and myrrh includes the following
steps: pulverizing, dissolving and extracting to obtain
volatility component, then using beta-CD to make mixing and
inclusion, cooling and filtering to obtain the invented
frankincense and myrrh extract. Before inclusion and after one
combined image structure of the volatile oil and beta-CD gets
obviously change, so that when the frankincense and myrrh are
used, it can reduce irritation to gastrointestinal tract, and
can reduce production of adverse reactions of abdominal pain,
nausea, vomiting, diarrhea, dyspepsia and anoraxia, etc. to
further raise medicine effect of frankincense and myrrh and
raise the preparation quality.  
  
The invention relates to the field of medicine, in particular
to a frankincense, myrrh optimization processes...  
  
The object of the present invention can be achieved by the
following measures:  
One kind of frankincense, myrrh optimized treatment process is
frankincense, myrrh become crushed particles With petroleum
ether, dissolved, extracted until a colorless, volatile
petroleum ether and volatile oil obtained, and then With A-CD
solution mixing, cooling, filtration can be.  
  
The invention will be further described in detail with
reference to Examples:  
  
process: take frankincense, myrrh, to crush a particle with
petroleum ether  
Solvent dissolved, extracted with Soxhlet extractor pumping
until colorless, and then in a water bath hood  
Within volatile petroleum ether to obtain volatile oil and
seal it back; Another A-CD was dissolved in distilled  
Water and placed DF-101 collector-type magnetic stirrer,
adding essential oil dissolved in ethanol,  
Maintaining a predetermined temperature, mixing a
predetermined time, and make up water, then in the
refrigerator to  
Chilled for 24 hours, with a dry pump suction filter, washed
with a small amount of ethanol, 60 ? dried for 2  
Hours, weighing, measuring oil content, and calculate the oil
utilization and yield...  
  
The results show that the temperature of the oil contained
utilization rate and the oil has a significant impact on the
yield of No significant effects feed ratio and stirring time
of oily rate has a significant impact on oil profits With a
yield rate and a significant effect



---

  
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excitability****CN103751386****Medicinal combination for inhibiting stallion sexual
excitability****CN103751385****TCM composition for treating mare mastitis****CN103751384****Medicinal combination for improving mare pregnancy rate****CN103751383****Medicinal combination for inhibiting mare oestrus****CN103751382****Fetus-protecting medicinal combination for mare at early
stage of pregnancy****CN103751381** **Pharmaceutical composition for induction of early-pregnant
mare abortion****CN103751380****TCM composition for treatment of mare ovarian cyst****CN103751379****TCM composition for treatment of mare hydrohytera****CN103751378****TCM composition for treatment of mare hysteromyoma****CN103751377****TCM composition for treatment of mare andromania****CN103751376****Pharmaceutical composition for raising mare sexual
excitation****CN103751375****Pharmaceutical composition for induction of mare
superovulation****CN103751374****TCM composition for treatment of mare failed in oestrus for
a long time****CN103751373****TCM composition for prevention of mare abortion****CN103751372****TCM composition for treatment of mare retained fetal
membranes****CN103751371****TCM composition for shortening mare luteal phase****CN103751370****TCM composition for raising stallion semen quality****CN103751369****Composite Chinese medicine for treating equus animal
orchitis****CN103751368****TCM composition for treatment of mare pyometra****CN103751367****TCM composition for treatment of mare ovarian atrophy****CN103751366****TCM composition for treatment of mare blennometritis****CN103751365****TCM composition for treatment of mare persistant corpus
luteum****CN103751364****Lotion with effect of bone righting****CN103751326****External TCM preparation for treating fasciitis and
preparation method thereof****CN103751310****TCM external preparation for treating intercostal neuralgia
and preparation method thereof****CN103751309****Anti-rheumatic, anti-inflammatory and antalgic
pharmaceutical composition****CN103751306****Plaster for treating rheumatism and preparation method
thereof****CN103736069** **TCM composition for treating protrusion of lumbar
intervertebral disc****CN103736067****Steaming therapy medicament for treating lumbocrural pain
and lumbar disc herniation****CN103736053****Tissue regeneration promoting plaster for traumatic
injuries****CN103736025****TCM preparation for treating insomnia and dreamful sleep****CN103736019****Medicament for treating hyperplasia of mammary glands and
preparation method thereof****CN103736016****Chinese herbal medicine formula for treating
arteriosclerosis and preparation method****CN103736007****Medicament for treating mammary hyperplasia****CN103736003****Chinese patent medicine for treating gastritis****CN103735979****Externally-used TCM lotion for treating mammary hyperplasia****CN103735953****Chinese medicinal mixture for treating perianal abscess****CN103735928****Plaster for treating cervical spondylosis****CN103735796****Pain relieving and inflammation diminishing compound
medicine for resisting rheumatalgia****CN103735777****Preparing method and use method of fire moxibustion
dredging dispersant for treating anemofrigid-damp arthralgia****CN103735766****TCM composition for treating hyperostosis and cold
arthritis and preparation method thereof****CN103735763****External medicinal liquor****CN103735759****Composition for treating toxic heat flaming-type systemic
scleroderma****CN103735747****Chinese medicinal formula for treating scald and burn****CN103735744****TCM spray for treating scalds and burns without scar****CN103735738****Preparation method of Chinese medicinal composition and
Chinese medicinal composition prepared by using preparation
method****CN103735712****Preparation method and application method of fire
moxibustion medicated thread for treating herpes zoster****CN103735651****Szechuan lovage rhizome health care wine for scrofula****CN103725577****Aggregation curcuma zedoary health-care wine****CN103725557****TCM composition for treating chronic atrophic gastritis****CN103721173****TCM composition used for treating stomachache****CN103721159****TCM preparation for treating functional dyspepsia****CN103721157****TCM formula for treating gastric diseases and preparation
method thereof****CN103721104****External TCM preparation for treating chronic nasosinusitis
and preparation method thereof****CN103721061****Frankincense health care wine for treatment of peptic ulcer****CN103721021****TCM composition used for treating pyogenic infection****CN103720978****TCM composition used for treating iliac vein thrombus****CN103720895****TCM prescription for treating cervical spondylosis and
preparation method thereof****CN103720893****TCM for treating spleen deficiency****CN103720868****Chinese herbal medicine for rapidly recovering after
fracture and preparation method thereof****CN103720855****Preparation method of liver-protecting medicine****CN103720811****Medicinal liquor for removing blood stasis and treating
bone fracture****CN103720807****TCM preparation for treating elytritis****CN103720749****Rheumatism patch and preparation method thereof****CN103705904****Hyperostosis patch and preparation method thereof****CN103705903****TCM preparation for treating pharyngitis****CN103705880****External TCM for treating supraclavicular or
infraclavicular (axillary) and inguinal lymphadenectasis****CN103705874****Steaming hot-compress paste for treating cervical
spondylosis and lumbar spondylosis****CN103705864****TCM for improving postoperative qi-yin deficiency of
thyroid cancer****CN103705863****External use medicinal liquor for relaxing tendons and
activating collaterals and preparation method thereof****CN103705858****TCM preparation for treating tenovaginitis of flexor
digitorum, as well as preparation and application thereof****CN103705852****Chinese medicament decoction for treating hyperostosis****CN103705801****TCM powder for stopping bleeding and diminishing
inflammation****CN103705735****Topical lotion for promoting to heal bone fractures****CN103705700****TCM preparation for treating acute gastroenteritis****CN103705692****TCM patch for treating cervical spondylosis****CN103705681****Ointment for treating rheumatism****CN103705679****Tong therapy medicine for treating knee osteoarthritis****CN103705673****Formula and preparation method of TCM for promoting
recovery and improving deficiency of qi and blood after
orthopedic surgery****CN103705621****Formula of paste for removing slough and promoting growth
of tissue regeneration****CN103705616****Externally applied TCM powder for treating burns and scalds****CN103705615****Method for preparing beauty treatment wax****CN103705408****Frankincense healthcare tea for peptic ulcer****CN103704391****TCM composition for treating amenorrhea****CN103690925****Moxibustion medicinal strip for treating rheumatic
arthralgia****CN103690905****Compound TCM preparation for treating trauma diseases such
as burn, scald, bedsore and the like****CN103690903****TCM decoction for treating stomach cancer****CN103690889****Plaster for relieving oppression and masses and preparation
method of plaster****CN103690887****External TCM fuming and washing lotion prescription for
treating gout****CN103690846****TCM formula for treating hyperplasia of mammary glands****CN103690722****TCM preparation for treating stroke****CN103690717****Muscle relaxing pills and preparation method thereof****CN103690714****External TCM foot bathing agent for warming and smoothing
foot blood vessels****CN103690708****TCM composition for treating dampness-heat-type hemorrhoids****CN103690702****Broad-spectrum antibacterial cream****CN103690698****TCM composition for treating blood-stasis-type hemorrhoids****CN103690658****TCM composition for treating intestinal-heat-type
hemorrhoids****CN103690640****Medicated wine for treating traumatic injury****CN103690623****TCM for treating prostatitis****CN103690614****TCM preparation for treating rheumatism****CN103690605****Preparation method of joint health care medicine oil****CN103690600****Puerpera health product****CN103689583****TCM formula for treating scapulohumeral periarthritis****CN103656604****Externally-applied medicine paste for treating burns and
preparation method of paste****CN103656593****TCM paste for treating cervical spondylosis and preparation
method of paste****CN103656592****Plaster capable of activating blood circulation to
dissipate stasis and preparation method thereof****CN103656578****Formula of neurologic surgery inflammation elimination and
pain relieving TCM****CN103656574****TCM for treating tumors and cancers****CN103656554****TCM tablet capable of relaxing meridian and activating
blood circulation and preparation method of tablet****CN103656523****TCM formula for treating gout****CN103656509****Application powder for removing toxicity and dredging
collaterals****CN103656506****TCM composition for treating diabetes complicated by
diabetic feet****CN103656488****TCM for curing thrombophlebitis****CN103656471****TCM honeyed pill for treating gastric cancer and
preparation method thereof****CN103656461****TCM for treating hysteromyoma****CN103656431****TCM for treating female hysteromyoma****CN103656430****TCM for treating hyperostosis****CN103656336****Medicine for treating optic atrophy and preparation method
of medicine****CN103656290****Externally-applied plaster and preparation method thereof****CN103656139****External application medicament for treating sprain****CN103656094****TCM capable of treating lung cancer****CN103656089****TCM powder for treating dental ulcer****CN103656088****TCM formula for treating varicosity****CN103656081****Externally-applied ointment for treating carbuncle and
furuncle and preparation method thereof****CN103656062****External-application plaster for treating hyperosteogeny****CN103656027****Special bone fracture treatment drug and preparation method
thereof****CN103656024****Pharmaceutical composition for treating rheumatism bone
disease and preparation method thereof****CN103656022****Buccal TCM formula for treating chronic pharyngitis****CN103656017****Preparation method of externally-used medicinal wine for
treating burns and scalds****CN103655944****Preparation method of anti-inflammatory TCM oil****CN103655934****TCM composition for treating prolapse of lumbar
intervertebral disc****CN103655897****Special TCM preparation for treating rheumatoid arthritis****CN103655895****Preparation method of external-application medicinal liquor
for treating arthritis****CN103655884****Unguent for treating scalds****CN103655818****TCM preparation for treating skin ulcers and preparation
method thereof****CN103655771****Preparation method of frankincense shower gel****CN103655331****Healthcare food for middle-aged women****CN103652880****TCM for treating tumor of chest wall and preparation method
thereof****CN103638476****TCM composition for treating thoracic obstruction****CN103638446****TCM composition capable of relieving pain****CN103638414****Internal medicinal liquor for treating traumatic injuries
and preparation method thereof****CN103638402****Medicament for treating wind-cold-dampness arthralgia and
preparation method of medicament****CN103638386****TCM decoction for treating intestinal carbuncle****CN103638308****Toxicity-removing and tissue regeneration-promoting paste
for treating ulcers and preparation method thereof****CN103638214****External TCM preparation for treating bedsore****CN103638173****Medicine for treating mycotic stomatitis****CN103638131****Traditional Chinese medicament preparation for fracture
healing****CN103638104****Antirheumatic health-care wine and preparation method
thereof****CN103627605****Soluble hemostatic gauze with functions of antisepsis and
anti-inflammation****CN103623461****TCM preparation for treating chronic gastritis and
preparation method thereof****CN103623388****External application medicine for treating eczematous
dermatitis and preparation method of powder of external
application medicine****CN103623309****Traditional Chinese herbal preparation for treating
thyromegaly and preparation method thereof****CN103623306****TCM formula for treating urinary calculus****CN103623284****TCM composition for treating hyperplasia of mammary glands****CN103623226****Compound medicine oil for treating scalds and burns and
preparation method thereof****CN103623198****Traumatic injury treatment paste and preparation method
thereof****CN103623162****Patch for promoting blood circulation to remove meridian
obstruction and eliminating cold to stop pain and preparation
method thereof****CN103623160****Soft tissue contusion treatment external washing TCM****CN103623043****Aromatic composition having stress-relieving and relaxing
effects and cosmetic composition containing same****CN103619322****Medicine for treating uterine prolapse and preparation
method thereof****CN103611144****Plaster for treating periostitis****CN103611134****Blood circulation promotion and pain alleviation gel and
preparation method thereof****CN103611133****Ointment for treating sore and furuncle and preparation
method thereof****CN103611084****TCM composition for treating scrofula****CN103611060****TCM composition for treating chronic appendicitis****CN103611001****Chinese medicinal anti-freckle composition, Chinese
medicinal anti-freckle preparation and Chinese medicinal
anti-freckle mask****CN103610926****Ointment for treating burns and scalds and preparation
method thereof****CN103610888****TCM composition for treating cervical erosion****CN103610880****Orally taken TCM for treating appendicitis of pregnancy****CN103610777****External Chinese medicinal composition for treating soft
tissue injuries****CN103610774****TCM for treating cerebral thrombosis****CN103610772****Foot-soaking TCM composition for treating diabetic feet****CN103610770****Cervical and lumbar rehabilitation pillow****CN103610360****Externally applied TCM for treatment of cervical
spondylosis****CN103599494****Externally-applied TCM ointment for treating traumatic
injury, catagma, old rheumatalgia and trauma and preparation
method thereof****CN103599441****TCM for treating female menopausal syndrome****CN103599406****Plaster having effects of promoting blood circulation to
remove blood stasis****CN103599402****Medicament for treating tuberculosis****CN103599375****TCM liquid extract for treating ankylosing spondylitis****CN103599294****TCM composition for treating fibroid****CN103599286****TCM ointment for treating osteoporosis****CN103599239****Eye cream and preparation method thereof****CN103599062****Externally used TCM wine for treating rheumatoid arthritis****CN103585614****Rheumatism ostalgia plaster****CN103585590****TCM for treating bone fracture and preparation method
thereof****CN103585579****TCM formula for relieving pain and removing paralysis****CN103585533****Spray for treating dermatophytosis****CN103585496****Medicinal liquor capable of relaxing muscles and
stimulating blood circulation rapidly and efficiently****CN103585375****TCM preparation for treating deep venous thrombosis of
lower limbs****CN103585315****Analgesic patch****CN103566343****Osteosynthesis TCM and preparation method thereof****CN103566305****Pellet used for treating bone fracture****CN103566278****TCM composition for treating toothache****CN103566233****TCM for treating mould****CN103566188****TCM for treating acute mastitis****CN103566154****Medicine for treating bone fracture****CN103566073****TCM enema agent for treating gynecologic inflammations****CN103566060****Medicament for treating herpes****CN103565989****TCM composition for treating breast pain and using method
thereof****CN103565985****TCM formula for treating cold dampness arthralgia****CN103565950****Swelling-eliminating and pain-relieving TCM capsule
preparation and preparation method thereof****CN103565925****Specific medicine for treating bedsore and promoting quick
healing of wound****CN103565921****Production method of health-care bone-strengthening wine****CN103555531****TCM composition for treating alactation****CN103550703****Medicament for treating breast cancer****CN103550695****Chinese medicinal composition for treating lumbar-leg pain****CN103550685****TCM formula of externally applied specific orthopaedic
dogskin plaster****CN103550648****External medicinal composition for treating pain from
rheumatism****CN103550620****TCM pills for treating lumbar spondylosis****CN103550617****Pharmaceutical composition for preventing and treating
cervical spondylosis and lumbar spondylosis****CN103550540****Drug for treating bone diseases****CN103550456****External TCM for treating rheumatic cervical spondylosis
and preparation method thereof****CN103550447****External preparation for treating hyperplasia of mammary
glands****CN103550442****TCM composition for treating hyperostosis****CN103550380****Medicinal liquor for treating intractable wind-cold pain****CN103550375****Capsule for expelling wind and damp****CN103550366****External tincture for treating wind-cold-dampness
arthralgia****CN103550365****Medicinal liquor for treating Bi pain****CN103550362****TCM plaster for treating pain in neck, shoulders, back and
legs****CN103550300****Bone strengthening and body building health care wine****CN103540509****Preparation method of postoperative pharmaceutical adjuvant
paste for anorectal diseases****CN103536959****TCM composition for treating dysmenorrheal****CN103536877****TCM for treating abdominal pain of endoretention of damp
heat****CN103536816****Traditional Chinese medicament for treating mammary gland
hyperplasia in lactation period****CN103536765****Medicine for treating lumbar disc herniation****CN103536760****Medicament for treating cystospasm and application thereof
to acupuncture point moxibustion****CN103536731****TCM composition with enhanced pain-relieving and calming
effects and preparation method thereof****CN103536701****Chinese medicinal ethosome gel patch for treating herpes
zoster and preparation method thereof****CN103536700****Drug for treating ischialgia****CN103536671****Osteosynthesis medicine for department of traumatology and
preparation method of osteosynthesis medicine****CN103536655****Chinese medicine composition for treating knee
osteoarthritis and preparation method of Chinese medicine
composition****CN103520654****TCM preparation used for treating gastritis****CN103520607****Medicinal liquor used for treating lumbocrural pain,
hyperostosis and sciatica****CN103520579****Compound essential oil for relieving sad mood****CN103520524****TCM pill for treating ronic pyogenic osteomyelitis****CN103520513****TCM for treating stasis-blocking-channel type chest
stuffiness and pains****CN103520459****Haemorrhoids medicine****CN103520453****Chinese medicinal patch for treating dysmenorrhea, and
preparation method and application thereof****CN103520437****External preparation for treating traumatic injury, stasis,
gall and soft tissue contusion****CN103520417****Pure TCM externally-applied bone-knitting paste****CN103520416****Medicament for treating traumatic injuries****CN103520415****External medicine for skin ulcer****CN103520345****TCM preparation used for treating traumatic injury****CN103520309****Plaster formula for treating waist, neck, shoulder and knee
pain****CN103520308****Externally-applied TCM capable of treating neurothlipsis
symptom caused by protrusion of intervertebral disc of human
body****CN103520307****Plaster formula for treating burns****CN103520259****Medicine used for treating orthopaedic diseases, and
preparation method thereof****CN103505697****TCM composition for treating primary bronchus lung cancer****CN103505670****Five-root decoction for treating infantile tonsillitis and
preparation method thereof****CN103505647****Externally applied TCM used for auxiliary treatment of
diabetes and complications of diabetes****CN103505545****Composition capable of growing and blackening hair****CN103505542****Scald treating ointment****CN103505502****Fracture rapid healing plaster prescription****CN103505499****Composite pawpaw glycoprotein icing powder and preparation
method thereof****CN103504108****TCM composition for treating cold abdominal pain, and
manufacturing method and application for TCM composition****CN103495146****Preparation method of TCM tablet for treating osteoporosis****CN103495011****Pharmaceutical composition and pharmaceutical preparation,
preparation method thereof and application thereof****CN103494999****Externally applied patch for treating gynecological myoma
of uterus and ovarian cyst****CN103494985****TCM for treating goat oral cavity ulceration and
preparation method thereof****CN103494984****TCM composition for treating intractable headache****CN103494980****TCM lotion for treating gynecological inflammations as well
as preparation method thereof****CN103494958****TCM for treating stiff neck****CN103494900****Method for preserving salted duck eggs with red cores by
using frying salt****CN103494249****Blood-lipid-lowering pure TCM solvent****CN103494188****Medicine for treating manic-depressive psychosis and
preparation method thereof****CN103479969****Chinese traditional medicine composition for preventing and
treating pig foot-and-mouth disease and preparation method
thereof****CN103479916****Tissue regeneration promoting ulcer recovering oil used for
treating diabetic foot ulcer****CN103479883****Chinese herbal composition for treating cervical, lumbar
and bone hyperplasia****CN103479840****TCM for treating ulcerative carbuncle****CN103479797****Compound essential oil for relieving aloneness****CN103479766****Preparation method of emulsifiable paste for physinatherapy****CN103479759****TCM composition for treating coronary heart disease angina
and application thereof****CN103479712****Formula and production method of ganoderma lucidum
blood-circulation-activating stasis-dissipating wine****CN103468546****Bone joint composite nutrient supplement and preparation
method thereof****CN103463624****Medicament for treating gynecological diseases****CN103463606****Plaster for treating frostbite and preparation method
thereof****CN103463595****Plaster for treating frostbite and preparation method of
plaster****CN103463594****Medicinal liquor for treating sprain and fracture and
preparation method of medicinal liquor for treating sprain and
fracture****CN103463572****TCM for treating periumbilial pains****CN103463546****TCM preparation for replenishing and activating blood and
dispelling wind and removing dampness****CN103463463****TCM preparation for treating rheumatism bone pain and
preparation method thereof****CN103463381****TCM for treating femoral head necrosis and using method
thereof****CN103463351****TCM composition for treating acute lumbar sprain****CN103463349****TCM for treating arthroncus of knee****CN103463304****TCM composition for treating eczema of scrotum as well as
preparation method and use thereof****CN103463297****Chinese patent medicine for treating herpes zostor****CN103463278****Mammary gland hyperplasia treatment drug composition and
preparation method thereof****CN103463276****Drug for treating acute injury pains****CN103463268****TCM liquid for external application and preparation process
thereof****CN103463267****TCM composition for treating lumbar disc herniation****CN103463241****TCM fumigation composition used for treating bone fracture
and using method thereof****CN103463233****FRANKINCENSE CHEWING GUM****WO2014003741****TCM COMPOUND GEL FOR EXTERNAL TREATMENT OF CANCER PAIN AND
PREPARATION METHOD FOR SAME****WO2014000452****TCM composition for treating chronic gastritis****CN103446559****Chinese medicinal composition used for stopping pain and
reducing swelling and preparation thereof****CN103446528****TCM ointment for treating burn and scald and preparation
method thereof****CN103446409****Pharmaceutical composition, pharmaceutical preparation** **CN103446398** **Externally applied plaster and oral medicament mainly
treating bone fracture and preparation method thereof****CN103446374****Externally applied medicine for treating hemorrhoids and
preparation method of externally applied medicine****CN103446363****TCM capsule preparation for treating lumbar disc herniation
and preparation method of TCM capsule preparation****CN103446360****Lavipeditum TCM preparation for curing talalgia****CN103446263****TCM composition for rapidly healing wounds****CN103446240****Anti-aging essential oil capable of whitening****CN103446011****Eye essential oil capable of reducing fine lines and
removing black eyes****CN103446010****TCM formula for treating rheumatic arthritis by TCM fuming
moxibustion therapy****CN103432558****TCM for treating scapulohumeral periarthritis and
preparation method thereof****CN103432537****TCM composition for treating endometriosis and preparation
method thereof****CN103432530****Traditional Kazakhstan enema pharmaceutical composition for
treating infertility and preparation method thereof****CN103432529****TCM composition for treating acute pancreatitis****CN103432469****External TCM composition for treating traumatic injuries,
carbuncle, furuncle, as well as skin and external diseases****CN103432396****TCM formula for treating femoral head necrosis by TCM
fuming moxibustion therapy****CN103432328****Preparation method for TCM for treating liver
depression-type acute cervical lymphnoditis****CN103432327****Externally used slough-removing tissue
regeneration-promoting powder for facilitating healing of open
wound, carbuncle, sore and ulceration****CN103432320****Traditional Kazakhstan externally applied pharmaceutical
composition for treating infertility and preparation method
thereof****CN103432314****TCM used for treating hemorrhoid and preparation method
thereof****CN103432303****TCM for treating osteomyelitis****CN103432297****TCM for treating urticaria****CN103432296****TCM preparation as well as preparation method and use****CN103432259****Herbal anti-hair loss shampoo****CN103432060****Neck nursing essential oil****CN103432033****Whitening and freckle-removing essential oil****CN103432032****Whitening essential oil capable of fading fine lines****CN103432031****Formula of decoction capable of relaxing muscles and
tendons, dispelling wind and strengthening body and bone, and
preparation method of decoction****CN103431458** **Chinese medicine for treating chronic soft tissue injury,
and preparation method thereof****CN103417887****Traditional Chinese herbal preparation for treating
prostatitis and diseases of urinary system****CN103417860****TCM preparation used for preventing and treating
postoperative complications of gastric cancer and preparation
method thereof****CN103417845****TCM composition for treatment of upper respiratory
infection and acute tonsillitis in children****CN103417817****Medicine composition for detoxicating and relieving sore
throat, and preparation method of medicine composition****CN103417795****TCM for treatment of cerebral hemorrhage****CN103417790****TCM for treating scald****CN103417782****TCM for treating surgical wounds****CN103417781****Bone fracture treatment plaster****CN103417780****Fixing powder****CN103417777****TCM for treating nerve headache and preparation method
thereof****CN103417681****TCM for treating lumbar disc herniation****CN103417631****Sterile and detumescent external medicine for treating
local pain and preparation method thereof****CN103417598****Moisturizing essential oil capable of removing blood
streaks on face of user****CN103417439****Moisturizing essential oil capable of shrinking pores****CN103417438****Chinese medicine composition for external use and
preparation method thereof****CN103405740****Chinese medicine preparation for treating joint pain of
middle aged and elderly people****CN103405733****External unguent for treating scald and burn and
preparation method thereof****CN103405731****TCM liniment for treating acnes and preparation method
thereof****CN103405698****Drug for treating hemiplegia and preparation method thereof****CN103405684****Plaster for treating bone disease****CN103405644****Plaster for treating skin and external diseases****CN103405627****TCM for treatment of knee osteoarthritis****CN103405564****Compound essential oil for enhancing happy feeling****CN103405549****Chinese medicine compound effective part with effect of
treating arthritis****CN103405487****Externally used compound TCM for treating cancer induced
bone pain****CN103394062****Medicine for treating ectopic pregnancy****CN103394039****Medicine for treating ovarian cyst****CN103394037****TCM composition used for treating urinary calculus****CN103394035****Medicament for treating sciatica****CN103394031****Bruising internal injury first-aid Chinese herbal medicine
composition and preparation method thereof****CN103394028****Anti-inflammatory resolutive liquid medicine for promoting
blood circulation to arrest pain****CN103393999****TCM for treating mammary tumor****CN103393985****Chinese medicinal composition for treating prostatitis and
its preparation method****CN103393956****TCM ointment for promoting postoperative wound healing, and
preparation method thereof****CN103393953****Tradtional Chinese medicine composition for treating bone
fracture and preparation method thereof****CN103393950****Drug for treatment of lumbago due to kidney-asthenia****CN103393904****Clinical-laboratory traumatic bactericidal
inflammation-diminishing drug and preparation method thereof,****CN103393902****Externally used TCM for treating hyperostosis and rheumatic
ostealgia and preparation method thereof****CN103393897****Bone-setting TCM decoction and preparation method thereof****CN103393895****Medicine for treating dysmenorrhea****CN103393877****Antirheumatic plaster and preparation method thereof****CN103393872****Externally used medicinal liquor for treating rheumatism,
arthralgia and traumatic injury****CN103393871****TCM composition for treating osteoarthritis****CN103393840****TCM for treating catatonic headache and preparation method
thereof****CN103393825****Medicine for treating sciatica****CN103393792****Application of frankincense extract in prevention and
treatment of cardio-cerebral-vascular disease or liver and
kidney injury****CN103393740****Decoction for treating liver cirrhosis****CN103386084****TCM patch****CN103386064****Externally applied medicinal liquor for curing pain****CN103386053****Liquid pain killer and preparation method thereof****CN103385996****Chinese herbal medicine composition for quick connection of
muscles and bones****CN103385985****Drug for treating cervical spondylosis****CN103385945****Formula for osteoproliferation and application method
thereof****CN103385944****Plaster for treating parotitis****CN103385942****Quick-acting rheumatism powder****CN103385930****Pharmaceutical composition for treating coronary heart
disease, preparation and preparation method thereof****CN103385921****TCM for treating hyperosteogeny****CN103385908****Rhinitis slow-release drug****CN103385907****Compound essential oil capable of fading eye fine lines****CN103385822****Compound essential oil for fading striae gravidarum and
obesity marks****CN103385810****Compound essential oil capable of fading spots****CN103385809****Externally used Chinese patent medicine for treating soft
tissue injury****CN103381259****TCM for treatment of hyperosteogeny and spondylopathy****CN103381235****Pain-killing paste for bone illness****CN103381231****Medicine for treating traumatic injuries, traumatic
arthralgia and pain caused by ecchymoma****CN103381230****TCM for treating trigeminal neuralgia and preparation
method thereof****CN103381224****Pharmaceutical composition for treating cervical vertebra
and lumbar vertebra diseases****CN103372183****Novel pure TCM spray for treating eczema****CN103372165****TCM for treating favus of scalp and preparation method
thereof****CN103372136****TCM for treating rheumatoid****CN103372115****Preparation method of TCM for treating snake-sore sequelae****CN103372094****TCM composition for treating hysteromyoma****CN103356969****Medicine for treating stomach cancer and preparation method
thereof****CN103356957****Chinese medicine composition for treating lumbar muscle
degeneration****CN103356953****Method for relieving cramp pain of bone and peripheral
tissue****CN103356950****TCM formula for treating costal chondritis****CN103356949** **Formula of TCM for treatment of scalds****CN103356896** **Method for extracting TCMs such as frankincense, myrrh and
rhizoma bletillae****CN103356893** **Aerosol spray for treating cervical spondylosis****CN103356864****Aerosol spray for treating cervical spondylosis****CN103356863****TCM for treating rheumatism****CN103356854****Aerosol spray for treating cervical spondylosis****CN103356850** **TCM preparation for treating femoral head aseptic necrosis****CN103356842****Chinese medicine decoction for early treatment of bone and
joint injury****CN103356825****Medicine for treating peptic ulcer and preparation method
thereof****CN103349728** **Compound essential oil for removing sense of fear****CN103349696**


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