A PHARMACEUTICAL COMPOSITION FOR REDUCING LOCAL FAT AND USES THEREOF

• US 20180250243A1
• Filed: 08/26/2016
• Published: 09/06/2018
• Est. Priority Date: 08/28/2015
• Status: Active Grant

• Current Assignee: Caliway Biopharmaceuticals Co., Ltd.
• Original Assignee: Caliway Biopharmaceuticals Co., Ltd.
• Inventors: LING, YU-FANG
• Granted Patent: US 10,610,496 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 36/82 Theaceae (Tea family), e.g. camellia
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 8/347 Phenols
• CPC Class Codes: A61K 8/86 Polyethers
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 19/06 for countering cellulitis

Abstract

The present invention provides a pharmaceutical composition for reducing localized fat, comprising drug-containing micelles made of surfactants, and curcumin encapsulated in said drug-containing micelles. This pharmaceutical composition for reducing localized fat can reduce the fat at the administration site, and has the advantages of high stability, high bioavailability for fat tissue, few side effects, and sustained release.

Claims

1. A pharmaceutical composition to be administered at a local site of a subject, comprising:

drug-containing micelles; and

curcuminoid encapsulated in said drug-containing micelles;

wherein, said drug-containing micelles are a microstructure formed by a pharmaceutically acceptable polyoxyethylene castor oil derivative, and the hydrophilic-lipophilic balance value (HLB value) of the polyoxyethylene castor oil derivative is greater than 10.

2. The pharmaceutical composition of claim 1, the polyoxyethylene castor oil derivative is at least one of Kolliphor ELP (also known as. Cremophor ELP), cremophor RH 40, and other polyoxyethylene castor oil derivatives, or combination thereof.

3. The pharmaceutical composition of claim 1, the weight ratio of the curcuminoid to the polyoxyethylene castor oil derivative is 1:

5˜

1;

500.

4. The pharmaceutical composition of claim 3, the weight ratio of the curcuminoid to the polyoxyethylene castor oil derivative is 1:

20˜

1;

150.

5. The pharmaceutical composition of claim 1, the concentration of curcuminoid in the pharmaceutical composition is 0.3˜

120 mg/g.

6. The pharmaceutical composition of claim 5, the concentration of curcuminoid in the pharmaceutical composition is 2˜

91 mg/g.

7. The pharmaceutical composition of claim 1, the diameter of the drug-containing micelles is 3˜

50 nm.

8. The pharmaceutical composition of claim 7, the diameter of the drug-containing micelles is 5˜

20 nm.

9. The pharmaceutical composition of claim 1, the curcuminoid is curcumin.

10. The pharmaceutical composition of claim 1, the pharmaceutical composition further comprises a pharmaceutically acceptable aqueous solution.

11. The pharmaceutical composition of claim 1, the pharmaceutical composition further comprises a second lipophilic drug-containing micelles;

the second lipophilic-drug containing micelle is a second microstructure formed by a second polyoxyethylene castor oil derivative, and a second lipophilic drug is encapsulated in said second drug-containing micelles.

12. The pharmaceutical composition of claim 11, the hydrophilic-lipophilic balance value (HLB value) of the second polyoxyethylene castor oil derivative is greater than 10.

13. The pharmaceutical composition of claim 11, the polyoxyethylene castor oil derivative is at least one of Kolliphor ELP (also known as. Cremophor ELP), cremophor RH 40, and other polyoxyethylene castor oil derivatives, or combination thereof.

14. The pharmaceutical composition of claim 11, the second lipophilic drug is at least one of quercetin, synephrin, puerarin, resveratrol, and other lipophilic drug except curcuminoid, or combination thereof.

15. The pharmaceutical composition of claim 11, the weight ratio of the curcuminoid to the second lipophilic drug is 30:

1˜

1;

10.

16. The pharmaceutical composition of claim 1, the pharmaceutical composition further comprises a hydrophilic drug.

17. The pharmaceutical composition of claim 16, the hydrophilic drug is at least one of green tea extract, epigallocatechin gallate, epicatechin, epicatechin gallate, epigallocatechin, gallocatechin gallate, gallocatechin, catechin gallate, catechin, epigallocatechin gallate (EGCG), caffeine, carnitine, L-carnitine, synephrine, chlorogenic acid, and other hydrophilic drugs, or combination thereof.

18. The pharmaceutical composition of claim 16, the weight ratio of the curcuminoid to the hydrophilic drug is 30:

1 to 1;

10.

19. A method for reducing the subcutaneous fat at a local site of a subject, comprising a step of administering a pharmaceutical composition to the local site of the subject, wherein, the pharmaceutical composition comprises:

drug-containing micelles; and

curcuminoid encapsulated in said drug-containing micelles;

wherein, the drug-containing micelle is a microstructure formed by a pharmaceutically acceptable non-ionic surfactant, and the hydrophilic-lipophilic balance value (HLB value) of the non-ionic surfactant is greater than 10.

20. The method of claim 19, the non-ionic surfactant is at least one of polysorbate 80 (Tween 80), 2-hydroxyethyl 12-hydroxyoctadecanoate (solutol HS 15), polyoxyethylene castor oil derivatives, and other non-ionic surfactants, or combination thereof.

21. The method of claim 20, the polyoxyethylene castor oil derivative is at least one of Kolliphor ELP (also known as. Cremophor ELP), cremophor RH 40, and other polyoxyethylene castor oil derivatives, or combination thereof.

22. The method of claim 19, the weight ratio of the curcuminoid to the non-ionic surfactant is 1:

5 to 1;

500.

23. The method of claim 19, the concentration of curcuminoid in the pharmaceutical composition is 0.3˜

120 mg/g.

24. The method of claim 19, the diameter of the drug-containing micelles is 3˜

50 nm.

25. The method of claim 19, the pharmaceutical composition further comprises a pharmaceutically acceptable aqueous solution.

26. The method of claim 19, the pharmaceutical composition further comprises a second lipophilic drug-containing micelles;

wherein, the second lipophilic drug-containing micelle is a second microstructure formed by a second non-ionic surfactant, and a second lipophilic drug is encapsulated in said second lipophilic drug-containing micelles.

27. The method of claim 26, the hydrophilic-lipophilic balance value (HLB value) of the second non-ionic surfactant is greater than 10.

28. The method of claim 26, the second non-ionic surfactant is at least one of polysorbate 80 (tween 80), 2-hydroxyethyl 12-hydroxyoctadecanoate (solutol HS 15), polyoxyethylene castor oil derivatives, and other non-ionic surfactants, or combination thereof.

29. The method of claim 28, the second non-ionic surfactant is at least one of Kolliphor ELP (Cremophor ELP), cremophor RH 40, and other polyoxyethylene castor oil derivatives, or combination thereof.

30. The method of claim 26, the second lipophilic drug is at least one of quercetin, synephrin, puerarin, resveratrol, and any lipophilic drug except curcuminoid, or combination thereof.

31. The method of claim 26, the weight ratio of the curcuminoid to the second lipophilic drug is 30:

1˜

1;

10.

32. The method of claim 19, the pharmaceutical composition further comprises a hydrophilic drug.

33. The method of claim 32, the hydrophilic drug is at least one of green tea extract, epigallocatechin gallate, epicatechin, epicatechin gallate, epigallocatechin, gallocatechin gallate, gallocatechin, catechin gallate, catechin, epigallocatechin gallate (EGCG), caffeine, carnitine, L-carnitine, synephrine, chlorogenic acid, and other hydrophilic drugs, or combination thereof.

34. The method of claim 19, the weight ratio of the curcuminoid to the hydrophilic drug is 30:

1 to 1;

10.

35. The method of claim 19, the step is to administer the pharmaceutical composition to the local site of the subject with a subcutaneous injection formulation, a subcutaneous fat layer injection formulation, a solution for implanted infusion, a cream formulation, a patch formulation, or other skin-absorption delivery systems.

36. The method of claim 19, the administered dosage of the pharmaceutical composition to be injected at the local site of the subject is 0.02˜

20 mg/cm².

37. The method of claim 19, the administered dosage of the pharmaceutical composition to be injected at the local site of the subject is 0.01˜

40 mg/kg.

38. The method of claim 19, the dosing frequency of the pharmaceutical composition to be administered at the local site of the subject is 1˜

12 times every other day to every 30 days.

39. The method of claim 19, the curcuminoid is curcumin.

40. The method of claim 19, the pharmaceutical composition further comprises at least one of a cosolvent, a suspending agent, and an oil phase excipient, or combination thereof.

41. The method of claim 40, the microstructure is co-formed by the non-ionic surfactant and at least one of the oil phase excipient and cosolvent.

42. A method for reducing body weight of a subject, comprising a step of administering a pharmaceutical composition to the subject, wherein, the pharmaceutical composition comprises:

drug-containing micelles; and

curcuminoid encapsulated in said drug-containing micelles;

wherein, the drug-containing micelle is a microstructure formed by a pharmaceutically acceptable non-ionic surfactant, and the hydrophilic-lipophilic balance value (HLB value) of the non-ionic surfactant is greater than 10.

43. The method of claim 42, the curcuminoid is curcumin.

44. The method of claim 42, the pharmaceutical composition further comprises a pharmaceutically acceptable aqueous solution.

45. The method of claim 42, the pharmaceutical composition further comprises a second lipophilic drug-containing micelles;

wherein, the second lipophilic drug-containing micelle is a second microstructure formed by a second non-ionic surfactant, a second lipophilic drug is encapsulated in said second lipophilic drug-containing micelles, and the second lipophilic drug is at least one of quercetin, synephrin, puerarin, resveratrol, and any lipophilic drug except curcuminoid, or combination thereof.

46. The method of claim 42, the pharmaceutical composition further comprises a hydrophilic drug, and the hydrophilic drug is at least one of green tea extract, epigallocatechin gallate, epicatechin, epicatechin gallate, epigallocatechin, gallocatechin gallate, gallocatechin, catechin gallate, catechin, epigallocatechin gallate (EGCG), caffeine, carnitine, L-carnitine, synephrine, chlorogenic acid, and other hydrophilic drugs, or combination thereof.

47. The method of claim 42, the step is to administer the pharmaceutical composition to a local site of the subject with a subcutaneous injection formulation, an intravenous injection formulation, or a subcutaneous fat layer injection formulation.

48. The method of claim 47, the administered dosage of the pharmaceutical composition to be injected at the local site of the subject is 0.2˜

16 mg/cm².

49. The method of claim 47, the administered dosage of the pharmaceutical composition to be injected at the local site of the subject is 0.4˜

40 mg/kg.

50. The method of claim 47, the dosing frequency of the pharmaceutical composition to be administered at the local site of the subject is 3˜

60 times every other day to every 20 days.

51. The method of claim 42, the pharmaceutical composition further comprises at least one of a cosolvent, a suspending agent, and an oil phase excipient, or combination thereof.

52. The method of claim 51, the microstructure is co-formed by the non-ionic surfactant and at least one of the oil phase excipient and cosolvent.

53. The method of claim 42, the step is to administer the pharmaceutical composition to the local site of the subject with a subcutaneous injection formulation, a subcutaneous fat layer injection formulation, an intravenous injection formulation, a solution for implanted infusion, a cream, a patch, or other skin-absorption delivery systems.