# US 9,040,069 B2 · Process for manufacturing a stationary state of crystalline polymer of a biodegradable polymer matrix carrying an active substance and a polymer matrix produced thereby > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,069 B2 - Document ID: US9040069B2 - Status: Granted - Kind: B2 - Application number: 11/482,484 - Filed: 2006-07-07 - Published: 2008-01-10 - Granted: 2015-05-26 - Earliest claimed: 2006-07-07 - Assignees: Biotronik Vi Patent AG - Applicants: Tobias Diener - Inventors: Tobias Diener - Web page: https://patentgrep.com/patent/US9040069B2 ## CPC - A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)} - A61L 31/10: Macromolecular materials - A61L 2300/00: Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) ## Abstract A method for manufacturing a stationary state of polymer crystallinity of an active substance charged polylactide matrix for a stent, comprising the steps of: preparing the active substance charged polylactide matrix containing (a) a polylactide in amorphous or semicrystalline modification or with amorphous domains, and (b) at least one active substance on a surface or in a cavity of the stent communicating with the surface; and heating of the active substance charged polylactide matrix to a temperature ranging from TG-20° C. to TS-10° C., where TG represents a glass transition temperature and TS a melting temperature of the crystallites of the polylactide. ## Claims ### Claim 1 A method for manufacturing a storage stable stationary state of polymer crystallinity of an active substance charged polylactide matrix for a stent, the method comprising: (i) preparing the active substance charged polylactide matrix containing, (a) a semicrystalline polylactide, wherein the polylactide has a glass transition temperature TG of from 60-70° C. and a melting temperature TS of from 170-180° C., with an average TG and TS, (TG+TS/2) of 115° C. to 125° C., where TG represents a glass transition temperature and TS a melting temperature of the crystallites of the polylactide, and (b) at least one active substance, wherein the active substance charged polylactide matrix is on a surface or in a cavity of the stent communicating with the surface; and (ii) heating the active substance charged polylactide matrix to a temperature ranging from 45° C. to 55° C. for one week to form the storage stable stationary state of polymer crystallinity of the active substance charged polylactide matrix containing less than 10% by weight of amorphous polymer domains that can be crystallized at room temperature based on the total weight of polylactide. ### Claim 2 (depends on 1) The method of claim 1, wherein the polylactide is a poly-L-lactide. ### Claim 3 (depends on 1) The method of claim 1, wherein step (i) is carried out by applying a finely dispersed aerosol to a surface of the stent by means of a rotary atomiser. ### Claim 4 (depends on 3) The method of claim 3, wherein the aerosol has an average droplet size of <70 μm. ### Claim 5 (depends on 3) The method of claim 3, wherein the aerosol is applied so as to apply a coating having a thickness on the lumen side in a range of about 3-7 μm. ### Claim 6 (depends on 1) The method of claim 1 wherein the active substance is a fibrate. ### Claim 7 (depends on 6) The method of claim 6 wherein the fibrate is a lipid reducer group fibrate. ### Claim 8 (depends on 7) The method of claim 7 wherein the lipid reducer group fibrate is bezafibrate. ### Claim 9 (depends on 1) The method of claim 1 wherein the storage stability is independent of the level of the active substance charged in the active substance charged polylactide matrix. ### Claim 10 (depends on 1) The method of claim 1 wherein the active substance elution is increased compared to the active substance elution of the active substance charged polylactide matrix without heating. ### Claim 11 (depends on 1) A stent with a polylactide matrix according to claim 1. ### Claim 12 A method for manufacturing a storage stable stationary state of polymer crystallinity of an active substance charged polylactide matrix for a stent, the method comprising: (i) preparing the active substance charged polylactide matrix containing, (a) a semicrystalline polylactide, wherein the polylactide has a glass transition temperature TG of from 60-70° C. and a melting temperature TS of from 170-180° C., with an average TG and TS, (TG+TS/2) of 115° C. to 125° C., where TG represents a glass transition temperature and TS a melting temperature of the crystallites of the polylactide, and (b) at least one active substance, wherein the active substance charged polylactide matrix is on a surface or in a cavity of the stent communicating with the surface; and (ii) heating the active substance charged polylactide matrix to a temperature ranging from 45° C. to 55° C. for one week to form the storage stable stationary state of polymer crystallinity of the active substance charged polylactide matrix containing less than 10% by weight of amorphous polymer domains that can be crystallized at room temperature based on the total weight of polylactide, and wherein an active substance elution is increased compared to an active substance elution of a polylactide matrix without heating. ### Claim 13 (depends on 12) The method of claim 12, wherein the polylactide is a poly-L-lactide. ### Claim 14 (depends on 12) The method of claim 12, wherein step (i) is carried out by applying a finely dispersed aerosol to a surface of the stent by means of a rotary atomiser, and wherein the aerosol has an average droplet size of <70 μm. ### Claim 15 (depends on 14) The method of claim 14, wherein the aerosol is applied so as to apply a coating having a thickness on the lumen side in a range of about 3-7 μm. ### Claim 16 (depends on 12) The method of claim 12 wherein the active substance is a fibrate. ### Claim 17 (depends on 16) The method claim 16 wherein the fibrate is benzfibrate. ### Claim 18 (depends on 12) The method of claim 12 wherein the storage stability is independent of the level of the active substance charged in the active substance charged polylactide matrix.