Sustained release formulations comprising very low molecular weight polymers

Patent metadata

Field	Value
Publication number	US-9724397-B2
Application number	US-44743107-A
Country	US
Kind code	B2
Filing date	Oct 26, 2007
Priority date	Oct 27, 2006
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

The present invention relates to a parenteral, sustained and controlled release, semisolid formulation comprising an end-capped oligomer and at least one active substance without any supplementary viscosity reducing agent or excipient.

First claim

The invention claimed is:

1. A composition comprising:
(a) an end-capped, biodegradable polymer or copolymer having a weight average molecular weight of from about 500 to about 5,000 Daltons;
wherein the polymer or copolymer is a polylactide, polyglycolide, poly(lactide-co-glycolide), poly(lactic acid), or poly(glycolic acid) that is end-capped with an alkyl moiety; and

(b) a pharmaceutically active substance;
wherein the pharmaceutically active substance is recombinant human growth hormone (rhGH), growth hormone releasing hormone (GHRH), insulin-like growth factor (IGF), a GLP-1 analog, luteinizing hormone releasing hormone (LHRH), LHRH analog, or somatostatin analog;

wherein the composition:
is a sustained and controlled release semi-solid that does not include diluents, plasticizers, solvents or excipients; and
releases the pharmaceutically active substance over a period of at least one week following administration in an aqueous physiological environment.

2. The composition of claim 1 , wherein the alkyl moiety is an alkyl group containing from 5 to 18 carbon atoms.

3. The composition of claim 1 , wherein the alkyl moiety is an alkyl group containing from 5 to 12 carbon atoms.

4. The composition of claim 1 , wherein the alkyl moiety is an alkyl group containing 5 carbon atoms.

5. The composition of claim 1 , wherein the composition forms a sustained release semi-solid formulation/depot implant at an application or injection temperature between about 15° and about 50° C.

6. The composition of claim 5 , wherein the composition forms a sustained release semi-solid formulation/depot implant at an application or injection temperature between about 25° and about 40° C.

7. The composition of claim 1 , wherein the molecular weight of the polymer or copolymer is between about 700 and 3,000 Daltons.

8. The composition of claim 1 , wherein the pharmaceutically active substance is recombinant human growth hormone (rhGH) or growth hormone releasing hormone (GHRH).

9. The composition of claim 1 , wherein the pharmaceutically active substance is an insulin-like growth factor (IGF) or a pharmaceutically acceptable salt thereof.

10. The composition of claim 1 , wherein the pharmaceutically active substance is a GLP-1 analog or a pharmaceutically acceptable salt thereof.

11. The composition of claim 1 , wherein the pharmaceutically active substance is luteinizing hormone releasing hormone (LHRH), a LHRH analog, or a pharmaceutically acceptable salt thereof.

12. The composition of claim 1 , wherein the pharmaceutically active substance is a somatostatin analog or a pharmaceutically acceptable salt thereof.

13. The composition of claim 1 , wherein about 0.001% to about 70% (w/w) of the composition is a pharmaceutically active substance or a mixture of pharmaceutically active substances.

14. A process for the preparation of the composition of claim 1 , comprising:
(a) introducing the active substance or mixture thereof into a first syringe;
(b) introducing the polymer or copolymer into a second syringe;
(c) fitting a piston onto the first syringe;
(d) fitting a piston onto the second syringe;
(e) connecting the first syringe with the second syringe using a cone connector;
(f) removing air from the first syringe; and
(g) mixing the contents of the first and second syringe,
wherein the process is carried out without adjunction of diluents, plasticizers, solvents, or excipients.

15. The process of claim 14 , wherein one or more steps is carried out at a temperature between about 5° C. and about 60° C.

16. The process of claim 14 , further comprising the step of mixing the polymer or copolymer with the active substance or mixture thereof at a temperature between about 5° C. and about 60° C.

17. The process of claim 16 , wherein the active substance or mixture thereof is a powder.

18. A composition made by the process of claim 16 .

19. The composition of claim 7 , wherein the polymer or copolymer has a weight average molecular weight of between about 800 and about 2,000 Daltons.

20. The composition of claim 13 , wherein about 0.1% to about 30% (w/w) of the composition is a pharmaceutically active substance or mixture of pharmaceutically active substances.

21. The composition of claim 20 , wherein about 2% to about 30% (w/w) of the composition is a pharmaceutically active substance or mixture of pharmaceutically active substances.

22. The process of claim 15 , wherein the temperature is room temperature.

23. The process of claim 16 , wherein the temperature is room temperature.

24. The process of claim 16 , wherein the mixing is performed in a blender.

25. The process of claim 24 , wherein the polymer or copolymer is first added to the blender and the active substance or mixture thereof is added while mixing.

26. The composition of claim 1 , wherein the insulin-like growth factor is IGF-1.

27. The composition of claim 1 , wherein the composition releases the pharmaceutically active substance over a period of at least one month following administration in an aqueous physiological environment.

28. The composition claim 1 , wherein the composition releases the pharmaceutically active substance over a period of at least 21 days following administration in an aqueous physiological environment.

29. The composition of claim 1 , wherein the alkyl moiety is a linear alkyl.

30. A composition consisting of:
(a) an end-capped, biodegradable polymer or copolymer having a weight average molecular weight of from about 800 to about 2,000 Daltons, or a mixture thereof;
wherein the polymer or copolymer is a polylactide, polyglycolide, poly(lactide-co-glycolide), poly(lactic acid), or poly(glycolic acid), and
wherein the polymer or copolymer is end-capped with an alkyl moiety; and

(b) at least one pharmaceutically active substance;
wherein the composition is a semi-solid.

31. The composition of claim 11 , wherein the LHRH analog is triptorelin.

32. The composition of claim 1 , wherein the pharmaceutically active substance is growth hormone releasing hormone (GHRH).

Assignees

• Cherif-Cheikh Roland
• De Sousa Delgado Anne-Paula
• Lacombe Frédéric
• Lachamp Laurence
• Bourissou Didier
• Ipsen Pharma Sas

Inventors

• Cherif-Cheikh Roland
• De Sousa Delgado Anne-Paula
• Lacombe Frédéric
• Lachamp Laurence
• Bourissou Didier

Classifications

• A61P5/34

  Gestagens · CPC title

• A61P5/10

  of the posterior pituitary hormones, e.g. oxytocin, ADH · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P31/10

  Antimycotics · CPC title