JP2015533305A5 - - Google Patents

Claims (38)

A medical device comprising:
With balloons;
A coating on at least a portion of the balloon;
Wherein the coating comprises particles of a pharmaceutical formulation,
Each particle of the pharmaceutical formulation is at least partially encapsulated in a polymeric material;
A medical device characterized by that.   The medical device of claim 1, wherein at least 50% of the surface area of the pharmaceutical formulation is encapsulated in the polymeric material.   The medical device of claim 1, wherein at least 75% of the surface area of the pharmaceutical formulation is encapsulated in a polymeric material.   The medical device of claim 1, wherein at least 90% of the surface area of the pharmaceutical formulation is encapsulated in the polymeric material.   The medical device of claim 1, wherein at least 95% of the surface area of the pharmaceutical formulation is encapsulated in the polymeric material.   The medical device of claim 1, wherein the polymer layer has an average thickness of 2 microns to 20 microns. The medical device according to claim 1, characterized in that the pharmaceutical preparation has a crystallinity of 25% to 95%. The medical device of claim 1, wherein the encapsulated pharmaceutical formulation has an average particle size of less than 1 micron. The medical device of claim 1, wherein the encapsulated pharmaceutical formulation has an average particle size of 1 to 10 microns. The medical device according to claim 1, wherein the weight ratio between the pharmaceutical formulation and the polymeric material is from 40:60 to 60:40. The medical device of claim 1, wherein the pharmaceutical formulation is at least partially encapsulated in the polymeric material by spray drying a mixture of the pharmaceutical formulation, the polymeric material, and the solvent. The medical device according to claim 11, wherein the mixture is a solution and the solvent is a polar aprotic solvent. The medical device according to claim 11, wherein the mixture is a slurry and the solvent is water. The medical device of claim 1, wherein the pharmaceutical formulation is at least partially encapsulated in the polymeric material by adding particles of the polymeric material to the pharmaceutical formulation in a rotating container. 15. The medical device of claim 14, wherein the particles of polymeric material have an average particle size from 10 microns to 100 microns. 15. The medical device of claim 14, wherein the particles of polymeric material are added at a rate of 100 to 1000 [mu] g per minute. The pharmaceutical formulation is at least partially encapsulated in the polymeric material by forming an emulsion-based mixture comprising the pharmaceutical formulation and the polymeric material and separating the pharmaceutical formulation encapsulated in the polymer from the emulsion-based mixture. The medical device of claim 1, characterized in that: The medical device according to claim 1, wherein the pharmaceutical preparation is rapamycin. The medical device of claim 1, wherein the polymeric material comprises a bioabsorbable polymer. Bioabsorbable polymers include: polylactide (PLA); poly (lactide-co-glycolide) (PLGA); polyanhydride; polyorthoester; poly (N- (2-hydroxypropyl) methacrylamide); poly (dl- Poly (l-lactide) (LPLA); polyglycolide (PGA); poly (dioxanone) (PDO); poly (glycolide-co-trimethylene carbonate) (PGA-TMC); poly (l- Poly (dl-lactide-co-glycolide) (PGA-DLPLA); poly (l-lactide-co-dl-lactide) (LPLA-DLPLA); poly (glycolide-) Co-trimethylene) carbonate-co-dioxanone (PDO-PGA-TMC), poly Alkenyl alcohol (PVA), poly-arginine, and medical device of claim 19 which is selected from the group, it is characterized in comprising a mixture or copolymer thereof. 21. The medical device of claim 20, wherein the bioabsorbable polymer is selected from the group consisting of PLGA, PVA, polyarginine, and mixtures thereof. The medical device according to claim 1, further comprising a binder deposited on the outer surface of the encapsulated particles of the pharmaceutical formulation. 23. The medical device of claim 22, wherein the weight ratio between the binder and the polymeric material is from 1:99 to 25:75. 23. The medical device of claim 22, wherein the binder is applied by spraying and drying a solution of the binder on the encapsulated particles of the pharmaceutical formulation. 25. The medical device of claim 24, wherein the solution includes a binder and water. The binders are polyarginine, polyarginine 9-L-pArg, DEAE-dextran (diethylaminoethyl cellulose-dextran), DMAB (didodecyldimethylammonium bromide), PEI (polyethyleneimine), TAB (tetradodecylammonium bromide) and 23. The medical device of claim 22, comprising at least one of DMTAB (dimethylditetradecyl ammonium bromide). 23. The medical device of claim 22, wherein the binder is polyarginine. 28. The medical device of claim 27, wherein the polyarginine has an average molecular weight of about 70 kDa. 28. The medical device according to claim 27, wherein the average molecular weight of polyarginine is 5-15 kDa. The medical device according to claim 1, wherein the encapsulated particles of the pharmaceutical preparation are deposited on the balloon by using an eSTAT coating process. The medical device of claim 1, wherein the medical device releases at least 3% of the pharmaceutical formulation upon inflation of the balloon. A method of forming crystalline rapamycin encapsulating a polymer, the method comprising:
  Forming an emulsion-based mixture comprising a pharmaceutical formulation and a polymeric material;
  Evaporating a portion of the emulsion-based mixture; and
  Filtering the remaining emulsion-based mixture
Including methods. 33. The method of claim 32, further comprising resuspending and lyophilizing the encapsulated pharmaceutical formulation. 35. The method of claim 32, wherein the emulsion-based mixture is formed by combining a first polymer solution, a second polymer solution, a third polymer solution, and a pharmaceutical formulation. The method of claim 34, wherein the first polymer solution comprises a first polymer and an organic solvent. 36. The method of claim 35, wherein the first polymer solution is mixed with the second polymer solution, allowing the organic solvent to evaporate. 35. The method of claim 34, wherein the second polymer solution has a polymer concentration of about 0.5% to about 2%. The emulsion-based mixture is a mixture of a first polymer solution and a second polymer solution to form an emulsion, a pharmaceutical formulation and a third polymer solution are mixed to form a suspension, and the emulsion and suspension 35. The method of claim 34, wherein the method is formed by combining liquids.