초록 ▼

The invention relates to a preparation comprising a carrier phase and at least one further phase which cannot be mixed with the carrier phase or only partially mixed therewith, wherein the change in ambient conditions alters the viscosity of the carrier phase. The invention also relates to a method

The invention relates to a preparation comprising a carrier phase and at least one further phase which cannot be mixed with the carrier phase or only partially mixed therewith, wherein the change in ambient conditions alters the viscosity of the carrier phase. The invention also relates to a method for the production thereof and to particles and implants containing said preparations. The inventive preparations can contain various active substances with a delayed release action.

대표청구항 ▼

The invention claimed is: 1. A method of forming a solid implant or solid microparticles in a subject, the method comprising the steps of: a) providing a liquid polymer-containing carrier phase, a second phase and optionally at least one active compound, said second phase being capable of forming a

The invention claimed is: 1. A method of forming a solid implant or solid microparticles in a subject, the method comprising the steps of: a) providing a liquid polymer-containing carrier phase, a second phase and optionally at least one active compound, said second phase being capable of forming a dispersion with the carrier phase; b) mixing the liquid polymer-containing carrier phase and the second phase to form a dispersion, said liquid polymer-containing carrier phase being the internal phase and said second phase being the external phase of the dispersion; and c) administering the dispersion to a subject thereby solidifying the polymer-containing carrier phase to form the solid microparticles or a solid implant in the subject. 2. The method of claim 1 further comprising the step of changing the viscosity of the carrier phase, wherein the change in viscosity is accomplished by contacting the dispersion with the subject, changing the pH of a medium to which the dispersion is exposed, changing the temperature of a medium to which the dispersion is exposed, changing the ionic strength of a medium to which the dispersion is exposed, or a combination thereof. 3. The method of claim 1, wherein the internal carrier phase of the dispersion has a particle size primarily smaller than about 200 μm prior to administration to the subject. 4. The method of claim 1, wherein the internal carrier phase of the dispersion has a particle size primarily in the colloidal size range prior to administration to the subject. 5. The method of claim 1 prior to the step of mixing, further comprising the step of: storing the carrier phase and second phase separately. 6. The method of claim 1 prior to the step of mixing, further comprising the step of: storing the carrier phase and second phase in contact with one another but in a non-dispersed or only partially dispersed state. 7. The method of claim 1 wherein the carrier phase comprises a carrier material comprising a water-soluble polymer or a polymer which is soluble in aqueous fluids. 8. The method of claim 1 wherein the carrier phase comprises a carrier material comprising a water-insoluble polymer or a lipid. 9. The method of claim 7 or 8 wherein the carrier material comprises a cellulose-derivative, acrylate-derivative, polylactide, polylactide-derivative, polysaccharide, polysaccharide-derivative, carrier melt, or a combination thereof. 10. The method of claim 1 further comprising the steps of: providing at least one active compound; and including the at least one active compound in the dispersion. 11. The method of claim 10 further comprising the step of: providing a viscosity-increasing substance, stabilizer, release modifying agent, substance that affects the residence time of the microparticles or implant at the site of administration, bioadhesive material, penetration enhancers, or a combination thereof. 12. The method of claim 10 wherein the at least one active compound is released over an extended period of time at the site of administration. 13. The method of claim 10 wherein an initial rapid release of the active compound at the site of administration is avoided. 14. The method of claim 1 wherein the carrier phase comprises water, an organic solvent or a mixture thereof. 15. The method of claim 14 wherein the organic solvent is selected from the group consisting of ethanol, acetone, butanol, ethylformate, pentanol, n-propanol, iso-propanol, tetrahyrdofuran, triethylcitrate, triacetin, propylene glycol, glycerol, polyethylene glycol, ethylacetate, methylacetate, dimethylformamide, dimethylsulfoxide, dimethylacetamide, 2-pyrrolidone, N-methyl-2-pyrrolidone and a mixture thereof. 16. The method of claim 14 wherein the second phase is miscible or partially miscible with water. 17. The method of claim 14 wherein the second phase is immiscible with water. 18. The method of claim 1 wherein the second phase comprises a natural, semisynthetic or synthetic lipid, oil, wax, triglyceride, glycerol, glycol, or a mixture thereof. 19. The method of claim 18 wherein the second phase comprises cottonseed oil, soybean oil, safflower oil, hydrated peanut oil, olive oil, castor oil, Miglycol, silicone oil, isopropylmyristate, ethyloleate, paraffin, propylene glycol, poly(ethylene glycol), or a mixture thereof. 20. The method of claim 1 further comprising the steps of: providing a third phase; and mixing the carrier phase and the second phase or mixing the dispersion with the third phase, wherein the second phase is immiscible or only partially miscible with the third phase. 21. The method of claim 1 further comprising the step of: providing a viscosity-increasing substance, stabilizer, release modifying agent, substance that affects the residence time of the microparticles or implant at the site of administration, bioadhesive material, penetration enhancer, or a combination thereof. 22. The method of claim 1 wherein the dispersion exhibits thixotropic rheological behavior. 23. The method of claim 1 wherein the step of administering comprises parenteral, peroral, subcutaneous, rectal, buccal, vaginal, nasal, sublingual, periodontal, or transdermal administration to the subject. 24. The method of claim 10 wherein the carrier phase comprises water, an organic solvent or a mixture thereof. 25. A system for forming solid microparticles or a solid implant in a subject, the system comprising: an administrable dispersion; at least one storage compartment; and administration means; wherein the administrable dispersion comprises a liquid polymer-containing carrier phase dispersed within a second phase and optionally comprises at least one active compound, the carrier phase being capable of forming a dispersion with the second phase; the at least one storage compartment retains the dispersion prior to administration; the dispersion is administrable to a subject by way of the administration means; the dispersion has been formed by mixing the carrier phase with the second phase and thereby forming the administrable dispersion; and the polymer-containing carrier phase in the dispersion solidifies and forms the solid microparticles or a solid implant after administration to a subject. 26. The system of claim 25 wherein the internal carrier phase of the dispersion has a particle size primarily smaller than about 200 μm prior to administration to the subject. 27. The system of claim 25 wherein the internal carrier phase of the dispersion has a particle size primarily in the colloidal size range prior to administration to the subject. 28. The system of claim 25 comprising: a first storage compartment capable of storing the carrier phase; and a second storage compartment capable of storing the second phase such that the carrier phase and second phase are separate; and dispersion means adapted to form a dispersion of the carrier phase within the second phase. 29. The system of claim 25 comprising one storage component capable of storing the carrier phase and second phase, prior to dispersing, in contact with one another but in a non-dispersed or only partially dispersed state; and dispersion means adapted to form a dispersion of the carrier phase within the second phase. 30. The system of claim 25 wherein the carrier phase comprises a carrier material comprising a water-soluble polymer or a polymer which is soluble in aqueous fluids. 31. The system of claim 25 wherein the carrier phase comprises a carrier material comprising a water-insoluble polymer or a lipid. 32. The system of claim 30 or 31 wherein the carrier material comprises a cellulose-derivative, acrylate-derivative polylactide, polylactide-derivative, polysaccharide, polysaccharide-derivative, carrier melt, or a combination thereof. 33. The system of claim 25 wherein the carrier phase comprises water, an organic solvent or a mixture thereof. 34. The system of claim 33 wherein the organic solvent is selected from the group consisting of ethanol, acetone, butanol, ethylformate, pentanol, n-propanol, iso-propanol, tetrahydrofuran, triethylcitrate, triacetin, propylene glycol, glycerol, polyethylene glycol, ethylacetate, methylacetate, dimethylformamide, dimethylsulfoxide, dimethylacetamide, 2-pyrrolidone, N-methyl-2-pyrrolidone and a mixture thereof. 35. The system of claim 25 wherein the second phase is miscible or partially miscible with water. 36. The system of claim 25 wherein the second phase is immiscible with water. 37. The system of claim 25 further comprising a third phase, wherein the third phase, the carrier phase and the second phase together form the dispersion, and the second phase is immiscible or only partially miscible with the third phase. 38. The system of claim 25 wherein the second phase comprises a natural, semisynthetic or synthetic lipid, oil, wax, triglyceride, glycerol, glycol, or a mixture thereof. 39. The system of claim 25 wherein the second phase comprises cottonseed oil, soybean oil, hydrated peanut oil, olive oil, castor oil, Miglyol, silicone oil, isopropylmyristate, ethyloleate, paraffin, propylene glycol, poly(ethylene glycol), or a mixture thereof. 40. The system of claim 25 further comprising at least one active compound in the dispersion. 41. The system of claim 40 further comprising a viscosity-increasing substance, stabilizer, release modifying agent, substance that affects the residence time of the microparticle or implant at the site of administration, bioadhesive material, penetration enhance, or a combination thereof in the dispersion. 42. The system of claim 40 wherein the at least one active compound is released over an extended period of time at the site of administration. 43. The system of claim 40 wherein an initial rapid release of at least one active compound at the site of administration is avoided. 44. The system of claim 25 further comprising a viscosity-increasing substance, stabilizer, release modifying agent, substance that affects the residence time of the microparticle or implant at the site of administration, bioadhesive material, penetration enhancers, or a combination thereof in the dispersion. 45. The system of claim 25 wherein the administration means is adapted for parenteral, peroral, subcutaneous, rectal, buccal, vaginal, nasal, sublingual, periodontal, or transdermal administration of the dispersion to a subject. 46. An administrable dispersion that forms a solid implant or solid microparticles in a subject to which it is administered, the dispersion comprising: an internal liquid polymer-containing carrier phase dispersed within an external second phase, the carrier phase being capable of forming a dispersion with the second phase; and optionally at least one active compound; wherein the polymer-containing carrier phase in the dispersion solidifies and forms the solid microparticles or a solid implant after administration to a subject. 47. The dispersion of claim 46 wherein the particle size of the dispersion is primarily smaller than about 200 μm in size prior to administration to the subject. 48. The dispersion of claim 46 wherein the particle size of the dispersion is primarily in the colloidal size range prior to administration to the subject. 49. The dispersion of claim 46 wherein the carrier phase comprises a carrier material comprising a water-soluble polymer or a polymer which is soluble in aqueous fluids. 50. The dispersion of claim 46 wherein the carrier phase comprises a carrier material comprising a water-insoluble polymer. 51. The dispersion of claim 49 or 50 wherein the carrier material comprises a cellulose-derivative, acrylate-derivative, polylactide, polylactide-derivative, polysaccharide, polysaccharide-derivative, carrier melt, or a combination thereof. 52. The dispersion of claim 46 wherein the carrier phase comprises water, an organic solvent or a mixture thereof. 53. The dispersion of claim 52 wherein the organic solvent is selected from the group consisting of ethanol, acetone, butanol, ethylformate, pentanol, n-propanol, iso-propanol, tetrahydrofuran, triethylcitrate, triacetin, propylene glycol, glycerol, polyethylene glycol, ethylacetate, methylacetate, dimethylformamide, dimethylsulfoxide, dimethylacetamide, 2-pyrrolidone, N-methyl-2-pyrrolidone and a mixture thereof. 54. The dispersion of claim 46 wherein the second phase is miscible or partially miscible with water. 55. The dispersion of claim 46 wherein the second phase is immiscible with water. 56. The dispersion of claim 46 further comprising a third phase, wherein the third phase, the carrier phase and the second phase together form the dispersion, and the second phase is immiscible or only partially immiscible with the third phase. 57. The dispersion of claim 46 wherein the second phase comprised a natural, semisynthetic or synthetic lipid, oil, wax, triglyceride, glycerol, glycol, or a mixture thereof. 58. The dispersion of claim 46 wherein the second phase comprises cottonseed oil, soybean oil, safflower oil, hydrated peanut oil, olive oil, castor oil, Miglyol, silicone oil, isopropylmyristate, ethyloleate, paraffin, glycerol, propylene glycol, poly(ethylene glycol) or a mixture thereof. 59. The dispersion of claim 46 further comprising at least one active compound in the dispersion. 60. The dispersion of claim 59 further comprising a viscosity-increasing substance, stabilizer, release modifying agent, substance that affects the residence time of the microparticle or implant at the site of administration, bioadhesive material, penetration enhancer, or a combination thereof in the dispersion. 61. The dispersion of claim 59 wherein the at least one active compound is released over an extended period of time at the site of administration. 62. The dispersion of claim 59 wherein an initial rapid release of at least one active compound at the site of administration is avoided. 63. The dispersion of claim 46 further comprising a viscosity-increasing substance, stabilizer, release modifying agent, substance that affects the residence time of the microparticle or implant at the site of administration, bioadhesive material, penetration enhancer, or a combination thereof in the dispersion. 64. The dispersion of claim 46 wherein the dispersion is administered to a subject by a parenteral, peroral, subcutaneous, rectal, buccal, vaginal, nasal, sublingual, periodontal, or transdermal route. 65. The method of claim 24 wherein the organic solvent is selected from the group consisting of ethanol, acetone, butanol, ethylformate, pentanol, n-propanol, iso-propanol, tetrahydrofuran, triethylcitrate, triacetin, propylene glycol, glycerol, polyethylene glycol, ethylacetate, methylacetate, dimethylformamide, dimethylsulfoxide, dimethylacetamide, 2-pyrrolidone, N-methyl-2-pyrrolidone and a mixture thereof.