Polymeric composition for solubilizing poorly water soluble drugs and process for the preparation thereof

{
  "publication_number": "US6616941B1",
  "country": "US",
  "kind": "B1",
  "title": "Polymeric composition for solubilizing poorly water soluble drugs and process for the preparation thereof",
  "abstract": "A composition capable of forming a micelle in body fluids or in an aqueous medium and that can be injected into the body undiluted or as a diluted solution in an aqueous medium and method of preparation are disclosed. The composition comprises an amphiphilic block copolymer having a hydrophilic poly(alkyleneglycol) component and hydrophobic biodegradable polymer component, suspended in a poly (alkyleneglycol) medium. Such composition is used in the solubilization and administration of a poorly water-soluble drug.",
  "claims": [
    "1. A composition capable of forming a polymeric micelle in a body fluid or an aqueous medium, said composition comprising an amphiphilic block copolymer having a hydrophilic poly(alkylene glycol) A block component and hydrophobic biodegradable polymer B block component, said amphiphilic block copolymer being suspended in a liquid poly(ethylene glycol) medium wherein the poly (ethylene glycol) is represented by the formula: R - O - CH 2 CH 2 - (O CH 2 CH 2) n - O - R wherein R is hydrogen, C 1 -C 4 alkyl, benzyl, or acyl; and n is an integer of 3-220, wherein the poly (ethylene glycol) has an average molecular weight in the range of 200 to 10,000 Daltons.",
    "2. The composition of claim 1, wherein the block copolymer is within the range of 5 to 95 wt %, and the poly(ethylene glycol) medium is within the range of 5 to 95 wt % based on the total weight of said composition.",
    "3. The composition of claim 1, wherein the amphiphilic block copolymer is selected from the group consisting of AB diblock, ABA triblock and BAB triblock copolymers.",
    "4. The composition of claim 3, wherein the amphiphilic block copolymer is selected from the group consisting of AB diblock and ABA triblock copolymers.",
    "5. The composition of claim 1, wherein the hydrophilic A block component is within the range of 40 to 80 wt % based on the total weight of the block copolymer.",
    "6. The composition of claim 1, wherein the hydrophilic poly(alkylene glycol) A block component is poly(ethylene glycol) or monomethoxy poly(ethylene glycol).",
    "7. The composition of claim 6, wherein the hydrophilic poly(alkylene glycol) has an average molecular weight in the range of 1,000 to 15,000 Daltons.",
    "8. The composition of claim 1, wherein the hydrophobic biodegradable polymer B block component is selected from the group consisting of polylactide, copolymer of lactide and glycolide, copolymer of D,L-lactide and glycolide, polycaprolactone, polyanhydride, polyorthoester, copolymer of lactide and 1,4-dioxan-2-one, and copolymer of caprolactone and 1,4-dioxan-2-one.",
    "9. The composition of claim 8, wherein the hydrophobic biodegradable polymer, has an average molecular weight in the range of 1,000 to 10,000 Daltons.",
    "10. A hydrophobic drug containing biodegradable polymeric composition capable of solubilizing said hydrophobic drug in a hydrophilic environment to form a solution, said composition comprising a hydrophobic drug physically entrapped within but not covalently bound to a biodegradable polymeric drug carrier comprising an amphiphilic block copolymer having a hydrophilic poly(alkylene glycol) component and hydrophobic biodegradable polymer component being suspended in a poly(ethylene glycol) medium wherein the poly (ethylene glycol) is represented by the formula: R - O - CH 2 CH 2 - (O CH 2 CH 2) n - O - R wherein R is hydrogen, C 1 -C 4 alkyl, benzyl, or acyl; and n is an integer of 3-220, wherein the poly (ethylene glycol) has an average molecular weight in the range of 200 to 10,000 Daltons.",
    "11. The composition of claim 10, wherein the hydrophobic drug is in the range of 0.1 to 50 wt % based on the total weight of the block copolymer.",
    "12. The composition of claim 10, wherein the hydrophobic drug has a solubility of less than 10 mg/mL.",
    "13. The composition of claim 12, wherein the hydrophobic drug is selected from the group consisting of anticancer agents, antifungal agents, steroids, antiinflammatory agents, sex hormones, immunosuppressants, antiviral agents, anesthetics, antiemetics, and antihistamine agents.",
    "14. The composition of claim 13, wherein the hydrophobic drug is selected from the group consisting of paclitaxel, camptothecin, doxorubicin, cisplatin, 5-fluorouracil, cyclosporine A, amphotericin B, itraconazole, ketoconazole, indomethacin, testosterone, estradiol, dexamethasone, prednisolone, and triamcinolone acetonide.",
    "15. The composition of claim 10, further comprising an organic solvent selected from the group consisting of ethanol, acetic acid, lactic acid, glycolic acid, N-methyl-2-pyrrolidone, benzyl alcohol, glycerin, N,N-dimethyl acetamide, propylene glycol, diethyl amine, and mixtures thereof.",
    "16. A method for preparing a hydrophobic drug containing biodegradable polymeric micelle composition capable of solubilizing said hydrophobic drug in a hydrophilic environment to form a solution, comprising the steps of: 1) preparing a mixture containing an amphiphilic block copolymer having a hydrophilic poly(alkylene glycol) component and hydrophobic biodegradable polymer component, a hydrophobic drug, and a poly(ethylene glycol); 2) subjecting the resulting mixture to one step selecting from the group consisting of: (a) stirring at 30 to 100° C.; (b) stirring at 30 to 100° C. while adding an organic solvent into said mixture; and (c) dissolving said mixture in an organic solvent followed by evaporating the solvent."
  ],
  "description_excerpt": "This application is a 371 of PCT/KR00/00885 filed on Aug. 10, 2000.\n\nThe present invention relates to a biodegradable polymeric composition containing a block copolymer having a hydrophilic poly(alkylene glycol) component and a hydrophobic biodegradable polymer component suspended in a poly(ethylene glycol) medium, and to a method for the preparation thereof. The composition can effectively solubilize a hydrophobic drug and forms a solution which can be stored as a stable liquid formulation. Furthermore, the composition can be injected into the body undiluted or as a diluted solution in an aqueous medium, and therefore is useful for the intravenous administration of poorly water soluble drugs.\n\nMany important drugs are hydrophobic and have limited solubility in water. In order to attain the expected therapeutic effect from such drugs, it is usually required that a solubilized form of the drug be administered to a patient. Therefore, solubilization of a poorly water soluble drug is key technology in the preparation of a formulation for oral or parenteral, especially intravenous, administration of the drug. Common methods used for solubilization of poorly water soluble drugs are: i) dissolving the drug in a co-solvent of a water-miscible organic solvent and water; ii) modifying the drug as a salt that can be soluble in water; iii) forming a soluble drug-complex using a complexing agent; and iv) micellizing the drug in an aqueous medium with a surfactant. (Leon Lachman, “The Theory and Practice of Industrial Pharmacy”, Lea & Febiger, Philadelphia, 1986).",
  "cpc": [
    "A61K 47/10",
    "A61K 9/1075",
    "C08L 101/14",
    "C08L 2203/02",
    "C08L 2205/05",
    "C08L 67/00",
    "C08L 67/04",
    "C08L 71/02"
  ],
  "ipc": [
    "A61K 31/337",
    "A61K 31/35",
    "A61K 31/365",
    "A61K 31/405",
    "A61K 31/495",
    "A61K 31/513",
    "A61K 31/565",
    "A61K 31/568",
    "A61K 31/573",
    "A61K 33/24",
    "A61K 38/00",
    "A61K 45/00",
    "A61K 47/10",
    "A61K 47/12",
    "A61K 47/16",
    "A61K 47/18",
    "A61K 47/22",
    "A61K 47/34",
    "A61K 9/107",
    "A61K 9/51",
    "C08L 101/14",
    "C08L 101/16",
    "C08L 67/00",
    "C08L 71/02"
  ],
  "assignees": [
    "Samyang Corp"
  ],
  "inventors": [
    "Min-Hyo Seo",
    "In-Ja Choi"
  ],
  "filing_date": "2000-08-10",
  "publication_date": "2003-09-09",
  "grant_date": "2003-09-09",
  "priority_date": "1999-08-14",
  "application_number": "US-80748701-A",
  "family_id": "19607214",
  "cited_by_count": 72,
  "citations": [
    "US5429826A",
    "US5449513A",
    "WO1995010265A1",
    "US5665428A",
    "US5702717A",
    "EP0921139A1",
    "KR19990069033A"
  ]
}