Drug-releasing system of biodegradable polymer type

• US 20040076676A1
• Filed: 08/20/2003
• Published: 04/22/2004
• Est. Priority Date: 02/27/2001
• Status: Active Grant

• Current Assignee: Kakuji Tojo, Senju Pharmaceutical Company Limited
• Original Assignee: Kakuji Tojo, Senju Pharmaceutical Company Limited
• Inventors: Fujikawa, Yoshiko, Tojo, Kakuji
• Granted Patent: US 7,850,993 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

A method for producing compression-melt molded product using polylactic acid powder is described. The method comprises the steps of: 1) heat-melting polylactic acid having a weight-average molecular weight of 3,000-40,000 at 140-220° C., 2) allowing the melted polylactic acid to cool down to solidify at an ordinary or a lower temperature, 3) pulverizing the solidified polylactic acid at an ordinary temperature into powder, and 4) compressing the powder or a mixture powder prepared by addition of another ingredient, e.g., a biologically active compound, to the carrier powder in a mold at an ordinary temperature to cause the polylactic acid to melt into a molded product of a predetermined shape.

Claims

1. A method for production of a polylactic acid-based compression-melt molded product comprising the steps of:

1) heat-melting polylactic acid having a weight-average molecular weight of 3,000-40,000 at 140-220°

C.,

2) allowing the melted polylactic acid to cool down to solidify at an ordinary or a lower temperature,

3) pulverizing the solidified polylactic acid at an ordinary temperature into powder, and

4) compressing the powder or a mixture powder prepared by addition of another ingredient to the carrier powder in a mold at an ordinary temperature to cause the polylactic acid to melt into a molded product of a predetermined shape.

3. The method for production of claim 1 or 2, wherein the polylactic acid is DL-polylactic acid, D-polylactic acid or L-polylactic acid.

4. The method for production of claim 1 or 2, wherein the polylactic acid is DL-polylactic acid and the weight-average molecular weight of the polylactic acid is 8,000-30,000.

5. The method for production of claim 1 or 2, wherein the polylactic acid is D-polylactic acid or L-polylactic acid and the weight-average molecular weight of the polylactic acid is 3,000-30,000.

6. The method for production of one of claims 1 to 5, wherein the weight ratio of the another ingredient or the biologically active compound to polylactic acid is not more than ⅖

in the mixture powder.

7. The method of one of claims 1 to 6, wherein the mold has a cylindrical inner surface and the mixture powder is compressed in the direction of the axis of the mold.

13. The method of one of claims 1 to 12, wherein the another ingredients or the biologically active compound is selected from the group consisting of antibiotics, antimicrobials, antivirals, vascularization suppressors, anti-glaucoma agents, anti-cataract agents, anticancer agents and vaccine antigens.

14. A molded product of polylactic acid obtainable according to the method of claim 1.

2. A method for production of a biodegradable polymer-based drug releasing system comprising the steps of:

1) heat-melting polylactic acid having a weight-average molecular weight of 3,000-40,000 at 140-220°

C.,

2) allowing the melted polylactic acid to cool down to solidify at an ordinary or a lower temperature,

3) pulverizing the solidified polylactic acid at an ordinary temperature into powder, and

4) mixing the powder with a powder of a biologically active compound and compressing thus prepared mixture powder in a mold at an ordinary temperature to cause the polylactic acid to melt into a molded product of a predetermined shape.

8. A method for production of a biodegradable polymer-based drug releasing system comprising the steps of:

1) heat-melting polylactic acid having a weight-average molecular weight of 3,000-40,000 at 140-220°

C.,

2) allowing the melted polylactic acid to cool down to solidify at an ordinary or a lower temperature,

3) pulverizing the solidified polylactic acid at an ordinary temperature into powder, and

4) compressing, at an ordinary temperature, the powder or a mixture powder prepared by mixing the powder with a powder of a biologically active compound in an amount giving a weight ratio of the latter powder to the former of not more than ⅖

in a mold which is removably provided with a column-like core cylinder placed along the axis of the mold, to form a molded product defining a column-like hollow region,

5) removing the core cylinder and either pouring into the hollow region a mixture powder prepared by mixing powder produced through a process in which polylactic acid having a weight-average molecular weight of 3,000-40,000 is heat-melted at 140-220°

C., then cooled down to solidify at an ordinary or a lower temperature and pulverized at an ordinary temperature and powder of a biologically active compound in an amount giving a weight ratio of the latter powder to the former of not more than ⅖

, or inserting into the hollow region a molded product produced by compressing the mixture powder at an ordinary temperature, and

6) compressing the mixture powder, or the molded product therefrom, in the hollow region at an ordinary temperature to cause the polylactic acid in the mixture powder to melt and the mixture powder to be molded appressed against the inner wall of the hollow region, thereby obtaining a united molded product.

9. The method for production of a biodegradable polymer-based drug releasing system of claim 8 comprising the steps of:

1) pouring in the mold onto the end face of the molded product with the exposed hollow region produced according to claim 8 powder produced by a process in which polylactic acid having a weight-average molecular weight of 3,000-40,000 is heat-melted at 140-220°

C., then cooled down to solidify at an ordinary or a lower temperature and pulverized at an ordinary temperature or a mixture powder prepared by mixing said powder and powder of a biologically active compound in an amount giving a weight ratio of the latter powder to the former of not more than ⅖

, and

2) compressing said powder or the mixture powder in the direction of the axis of the mold at an ordinary temperature to cause the polylactic acid to melt, thereby molding the polylactic acid powder or the mixture powder, thus giving one united molded product together with the molded product produced according to claim 8.

10. A method for production of a biodegradable polymer-based drug-releasing system comprising the steps of:

1) heat-melting polylactic acid having a weight-average molecular weight of 3,000-40,000 at 140-220°

C.,

2) allowing the melted polylactic acid to cool down to solidify at an ordinary or a lower temperature,

3) pulverizing the solidified polylactic acid at an ordinary temperature into powder, and

4) compressing, at an ordinary temperature, the powder or a mixture powder prepared by mixing the former powder with a powder of a biologically active compound in an amount giving a weight ratio of the latter powder to the former of not more than ⅖

, in a mold which is removably provided with a column-like core cylinder placed along the axis of the mold to form a molded product defining a column-like hollow region,

5) removing the core cylinder and pouring into the hollow region a biologically active compound or a composition containing the same,

6) pouring onto the end face of the molded product with the exposed hollow region, powder produced by a process in which polylactic acid having a weight-average molecular weight of 3,000-40,000 is heat-melted at 140-220°

C., then cooled down to solidify at an ordinary or a lower temperature and pulverized at an ordinary temperature or a mixture powder prepared by mixing said powder and powder of a biologically active compound in an amount giving a weight ratio of the latter powder to the former of not more than ⅖

, and

7) compressing said powder or the mixture powder in the direction of the axis of the mold at an ordinary temperature to cause the polylactic acid to melt, thereby molding the polylactic acid powder or the mixture powder, thus giving one united molded product containing in the hermetically sealed hollow region a biologically active compound or a composition thereof.

11. The method of one of claims 8-10, wherein the polylactic acid is selected from the group consisting of DL-polylactic acid having the weight-average molecular weight of 8,000-30,000 and D- or L-polylactic acid having the weight-average molecular weight of 3,000-30,000.

12. The method of one of claims 8 to 11, wherein the bulk density of the molded product of polylactic acid is 700-4,000 mg/cm³ in the produced biodegradable polymer-based drug releasing system.

15. A biodegradable polymer-based drug releasing system obtainable according to the method of one of claims 2 to 13.