Pharmaceutical solutions and emulsions containing taxol

{
  "publication_number": "US5407683A",
  "country": "US",
  "kind": "A",
  "title": "Pharmaceutical solutions and emulsions containing taxol",
  "abstract": "Compositions of matter are provided comprising a pharmaceutically effective amount of taxol or a tumor-active analog thereof solubilized in a pharmaceutically acceptable carrier comprising an oil having a dipole moment of between about 0.5 Debyes and about 2.0 Debyes, and preferably between about 1.6 and about 1.7 Debyes. Oils from marine organisms having an ether lipid as a major component thereof are preferred. Methods of solubilizing taxol or tumor-active taxol analogs in the pharmaceutically acceptable oils of this invention are provided comprising forming a first solution by dissolving taxol in a preliminary solvent such as an anhydrous alcohol, then adding sufficient oil to solubilize said first solution. Taxol-in-oil solutions are used to prepare oil-in-water emulsions for pharmaceutical use in anti-tumor therapy by means known to the art using known surfactants. Self-emulsifying glasses comprising taxol or tumor-active taxol analogs are also provided comprising a water-soluble, nonsurface active matrix compound and taxol-oil solutions. Emulsions are readily formed from such glasses by contacting the glass with an aqueous phase.",
  "claims": [
    "1. A composition of matter comprising a pharmaceutically effective amount of taxol or a tumor-active analog thereof, completely solubilized in a squalene or squalane oil.",
    "2. The composition of matter of claim 1 comprising a pharmaceutically effective amount of taxol completely solubilized in said squalene or squalane oil.",
    "3. The composition of matter of claim 2 which contains at least about 0.5 mg/ml taxol.",
    "4. The composition of matter of claim 3 in emulsion form.",
    "5. The emulsion of claim 4 which does not contain a surfactant.",
    "6. A composition of matter consisting essentially of a pharmaceutically effective amount of taxol completely solubilized in a squalene or squalane oil.",
    "7. The composition of matter of claim 6 containing about 10 mg/ml of taxol.",
    "8. A method for solubilizing taxol or a tumor-active taxol analog in a pharmaceutically acceptable carrier which is a squalene or squalane oil comprising the steps of: (a) solubilizing taxol or said taxol analog in an anhydrous alcohol; (b) mixing the alcohol solution of (a) with a sufficient amount of said pharmaceutically acceptable carrier to solubilize said alcohol solution therein; and (c) removing said anhydrous alcohol from said carrier solution formed in step (b) by rotary evaporation thereby resulting in a carrier solution in which said taxol or taxol analog is completely solubilized in said squalene or squalane oil."
  ],
  "description_excerpt": "This application is a C-I-P of Ser. No. 07/830,058, filed Feb. 3, 1992, which is a C-I-P of Ser. No. 07/531,847, filed Jun. 1, 1990, both now abandoned.\n\nThis invention is in the field of pharmaceutical compositions, specifically compositions containing the anti-cancer drug, taxol.\n\nTaxol is a poorly water soluble alkaloid isolated from several species of Western Yew. Taxol exhibits antimitotic properties and is presently undergoing phase I clinical trials for the treatment of cancers. Taxol has been shown to be active against leukemia, colon, breast, melanoma, sarcomas, and Lewis lung tumor systems. Tarr et al. (1987) Pharm. Res. 4:162-165; Horwitz (1992) TIPS 13:134-131. In vitro studies indicate that concentrations of taxol (0.1-10.0 μg/ml, stabilize microtubules, thus disrupting normal cell division. Rowinsky et al. (1990) J. Natl. Cancer Inst. 82:1247-1259.\n\nTaxol is a complex diterpene having a taxane ring system with a four-membered oxetane ring and an ester sidechain at position C-13, as follows: ##STR1##\n\nIn an attempt to increase taxol's solubility and develop more feasible clinical formulations, investigators have acylated carbons of taxol's taxene ring at the 7-position and 10-position. These efforts have yielded compounds that retain activity. Rowinsky et al. (1990) J. Natl. Cancer Inst. 82:1247-1259.\n\nBecause of its poor solubility in water and many oils, taxol has been administered in formulations using cremophors. Cremophors are polyoxyethylated castor oils. The current Sigma taxol formulation most widely used consists of ethanol:cremophor EL:isotonic saline (5:5:90).",
  "cpc": [
    "A23D 7/00",
    "A61K 31/335",
    "A61K 47/06",
    "A61K 47/44",
    "A61K 9/0019",
    "A61K 9/107"
  ],
  "ipc": [
    "A21D 10/00",
    "A21D 2/18",
    "A23D 7/00",
    "A61K 31/335",
    "A61K 47/06",
    "A61K 47/44",
    "A61K 8/06",
    "A61K 9/107"
  ],
  "assignees": [
    "Research Corp Technologies Inc"
  ],
  "inventors": [
    "Merrick L. Shively"
  ],
  "filing_date": "1992-10-01",
  "publication_date": "1995-04-18",
  "grant_date": "1995-04-18",
  "priority_date": "1990-06-01",
  "application_number": "US-95528292-A",
  "family_id": "25496612",
  "cited_by_count": 137,
  "citations": [
    "US3723134A",
    "US5011532A",
    "US5032400A"
  ]
}