{
    "title": "HydroxyChloroQuine Patents : Synthesis & Therapy",
    "inventor_name": null,
    "publication_year": null,
    "device_name": null,
    "goal": "Provide an efficient, environmentally friendly method for preparing and refining hydroxychloroquine and its sulfate with high purity and controlled impurity levels.",
    "problem_addressed": "Existing hydroxychloroquine synthesis methods suffer from low yields, high impurity levels, use of toxic solvents (e.g., phenol, chloroform), hazardous high-pressure equipment, and large amounts of hazardous waste.",
    "concept_summary": "The invention discloses a purification process that crystallizes crude hydroxychloroquine in a mixed solvent of a ketone (e.g., acetone, methyl ethyl ketone) and an ester (e.g., ethyl acetate). The process includes controlled temperature crystallization, filtration, washing, and optional pH-adjusted extraction steps using sodium hydroxide. The method yields hydroxychloroquine of >99.9 % purity and hydroxychloroquine sulfate of >99.8 % purity while minimizing toxic solvents and waste.",
    "detailed_description": null,
    "category": "Chemistry & Chemical Processes",
    "principles": [
        "Crystallization",
        "Solvent extraction",
        "pH adjustment",
        "Inert-gas protection",
        "Temperature control"
    ],
    "scientific_domains": [
        "Chemistry",
        "Pharmaceutical Sciences",
        "Chemical Engineering"
    ],
    "mechanisms_of_action": [
        "Crystallization from mixed ketone/ester solvent",
        "Filtration and washing of crystals",
        "Alkaline extraction of crude product",
        "pH-controlled precipitation"
    ],
    "materials": [
        "acetone",
        "methyl ethyl ketone",
        "methyl isobutyl ketone",
        "2-pentanone",
        "methyl acetate",
        "ethyl acetate",
        "propyl acetate",
        "isopropyl acetate",
        "butyl acetate",
        "acetic acid",
        "4,7-dichloroquinoline",
        "5-(N-ethyl-N-2-hydroxyethylenediylamino)-2-pentylamine (hydroxychloroquine side-chain compound)",
        "sodium hydroxide",
        "sodium carbonate",
        "potassium hydroxide",
        "water",
        "nitrogen",
        "argon",
        "helium",
        "carbon dioxide"
    ],
    "energy_sources": [],
    "inputs": [
        "crude hydroxychloroquine (>=92 % content)",
        "mixed solvent (ketone + ester)",
        "inert gas (N_2, Ar, He, CO_2)",
        "aqueous sodium hydroxide solution (6-10 % w/w)",
        "water"
    ],
    "outputs": [
        "refined hydroxychloroquine (purity >99.9 %)",
        "hydroxychloroquine sulfate (purity >99.8 %)"
    ],
    "claimed_performance": "Purity of refined hydroxychloroquine >99.9 %; single impurity <=0.06 %; total impurities <0.04 %. Purity of hydroxychloroquine sulfate >=99.8 %; single impurity <=0.06 %.",
    "experimental_evidence": "The abstract states that the refined product can reach 99.9 % purity with impurity limits as described, but no quantitative experimental data or independent replication is provided.",
    "replication_status": null,
    "keywords": [
        "hydroxychloroquine",
        "purification",
        "crystallization",
        "solvent mixture",
        "pharmaceutical synthesis",
        "API manufacturing"
    ],
    "related_technologies": [
        "High-performance liquid chromatography (HPLC) analysis",
        "Solvent extraction techniques",
        "Industrial crystallization equipment"
    ],
    "controversy_level": "low",
    "confidence_score": 0.95,
    "practicability_score": 0.85,
    "fringe_score": 0.1,
    "evidence_strength": 0.4,
    "risk_score": 0.2,
    "trl_estimate": 7,
    "source_urls": [
        "https://worldwide.espacenet.com/patent/search"
    ],
    "organizations": [],
    "applications": [
        "Production of antimalarial drug hydroxychloroquine",
        "Manufacture of hydroxychloroquine sulfate tablets for lupus erythematosus and rheumatoid arthritis"
    ],
    "limitations": [
        "Requires handling of organic solvents (ketones, esters) that are flammable",
        "Needs inert-gas atmosphere and precise temperature control",
        "Scale-up may be limited by solvent recovery infrastructure"
    ],
    "open_questions": [
        "Economic comparison with existing industrial processes",
        "Environmental impact of solvent waste and recovery efficiency",
        "Long-term stability of the high-purity product during storage"
    ],
    "red_flags": [],
    "evidence_quotes": [
        "The purity of the refined product of the hydroxychloroquine prepared by the method can reach 99.9%, a maximum content of a single impurity is controlled within 0.06%, and a total content of other impurities is lower than 0.04%;",
        "Purity of the hydroxychloroquine sulfate prepared from the hydroxychloroquine can reach 99.8%, and a maximum content of a single impurity is controlled within 0.06%.",
        "The mixed solvent is preferably one or more of methyl ethyl ketone and ethyl acetate, acetone and methyl acetate, 2-pentanone and isopropyl acetate, and methyl isobutyl ketone and butyl acetate.",
        "The ketone solvent may be a C3 to C9 alkyl ketone, particularly acetone, methyl ethyl ketone, methyl isobutyl ketone, or 2-pentanone.",
        "The ester solvent may be an acetate solvent, particularly methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, or acetic acid."
    ]
}