METHOD OF PRODUCING A COMPOSITION FROM AN OLEOGEL AND AN AQUEOUS GEL AND THE COMPOSITION

• US 20110158920A1
• Filed: 12/31/2007
• Published: 06/30/2011
• Est. Priority Date: 12/29/2006
• Status: Abandoned Application

• Current Assignee: Aptys Pharmaceuticals SAS
• Original Assignee: Ardana Bioscience Limited
• Inventors: Fisher, Julian Robert Walker, Morley, Timothy
• Application Number:
  US12/521,715
• Publication Number:
  US 20110158920A1
• Time in Patent Office: Days
• US Class Current: 424/59
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/375 the alcohol moiety containing more than one hydroxy group
• CPC Class Codes: A61K 8/63 Steroids; Derivatives thereof
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/8147 Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

A method for producing a bigel, the method comprising: (a) providing an oleogel comprising at least one oily agent gelled with at least one cellulose polymer; (b) providing an aqueous gel comprising at least one component whose viscosity is pH dependent, such as a carbomer; (c) mixing the oleogel and the aqueous gel together to form a bigel; and (d) subsequently adjusting the viscosity of the bigel under high flow and low shear stirring to obtain a bigel of a desired viscosity.

Claims

1. A method of producing a bigel, the method comprising:

(a) providing an oleogel comprising at least one oily agent gelled with at least one cellulose polymer;

(b) providing an aqueous gel comprising at least one component whose viscosity is pH dependent;

(c) mixing the oleogel and the aqueous gel together to form a bigel; and

(d) subsequently adjusting the viscosity of the bigel under high flow and low shear mixing to obtain a bigel of a desired viscosity.

2. A method according to claim 1 wherein the at least one cellulose polymer in the oleogel is selected from ethylcellulose, non-sodium carboxymethylcellulose, and mixtures thereof.

3. A method according to claim 1 wherein the at least one cellulose polymer in the oleogel is ethylcellulose.

4. A method according to claim 3 wherein the ethylcellulose is present in a proportion of between about 0.05% and 9% by weight of the bigel composition.

5. A method according to claim 1 wherein the oily agent in the oleogel is selected from mono-, di-, and triglycerides of synthetic, semi-synthetic and natural origin, and mixtures thereof.

6. A method according to claim 5 wherein the mono-, di-, and triglycerides of semi-synthetic origin comprise a mixture of polyoxy ethylenated oleic glycerides obtained by alcoholysis of natural plant oil.

7. A method according to claim 5 wherein the mono-, di-, and triglycerides of natural origin are selected from oils of plant origin, such as sweet almond oil, argan oil and palm oil.

8. A method according to claim 1 wherein the oily agent comprises a mixture of capric/caprylic triglycerides.

9. A method according to claim 1 wherein the oleogel further comprises one or both of propylene glycol isostearate and propylene glycol laurate, each present, independently, in a proportion of between about 0.1 and 5% by weight of the bigel composition.

10. A method according to claim 9 wherein the oleogel comprises ethylcellulose, propylene glycol isostearate and propylene glycol laurate and an oily agent.

11. A method according to claim 10 wherein the ethylcellulose, propylene glycol isostearate and propylene glycol laurate are present, in total, in a proportion of between about 2% and 6% by weight of the bigel composition.

12. A method according to claim 10 wherein the ethylcellulose, propylene glycol isostearate and propylene glycol laurate are present, in relative proportions of about 2-10:

2-10;

80-96, respectively.

13. A method according to claim 1 wherein step (a) of providing an oleogel, comprises making an oleogel as defined in any of claims 1-12.

14. A method according to claim 1 wherein the aqueous gel comprises at least one gelling agent whose viscosity varies and is pH dependent, selected from carbomers and sodium carboxymethylcellulose, and mixtures thereof.

15. A method according to claim 14 wherein the carbomer is selected from Carbopol®

Ultrez 10, Carbopol®

71G, Carbopol®

910, Carbopol®

934, Carbopol®

934P, Carbopol®

940, Carbopol®

971P, Carbopol®

974, Carbopol®

974P, Carbopol®

980, Carbopol®

981, and Carbopol®

1342 NF.

16. A method according to claim 14 wherein the aqueous gel further comprises at least one gelling agent selected from poloxamers (Pluronics®

), acacia, alginic acid, bentonite, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulo se, gelatin magnesium aluminum silicate (Veegum®

), methylcellulose, polyvinyl alcohol, sodium alginate, tragacanth, and xanthan gum, and mixtures thereof.

17. A method according to claim 14 wherein the aqueous gel has a viscosity of between 100-1,000 cP (100-1,000 mPa·

s) when measured using a Lamy VRM-08 with an MS DIN 1.9 module at 23°

C.

18. A method according to claim 14 wherein the aqueous gel has a pH of between 2.5 and 4.

19. A method according to claim 1 wherein step (b) of providing an aqueous gel comprises making an aqueous gel comprising at least one gelling agent whose viscosity varies and is pH dependent.

20. A method according to claim 1 wherein the oleogel and aqueous gel are mixed in step (c) using high-shear mixing.

21. A method according to claim 1 wherein the at least one component whose viscosity is pH dependent comprises sodium carboxymethylcellulose, and the oleogel and aqueous gel are mixed in step (c) using low-shear mixing.

22. A method according to claim 1 wherein the adjustment step (d) comprises adding a pH adjusting agent selected from sodium hydroxide, potassium hydroxide, sodium methylparaben, sodium propylparaben, amino methyl propanol, sodium EDTA and triethanolamine.

23. A method according to claim 1 wherein adjusting step (d) comprises bringing the pH to between pH 4 and pH 6.

24. A method according to claim 1 wherein adjusting step (d) comprises bringing the pH to between pH 6 and pH 7.5.

25. A method according to claim 1 wherein the adjustment in step (d) raises the viscosity of the bigel to between 1,000-30,000 cP (1-30 Pa·

s), and preferably between 20,000-30,000 cP (20-30 Pa·

s), measured using a Lamy VRM-08 with an MS DIN 1.9 module at 23°

C.

26. A method according to claim 1 wherein the adjustment in step (d) raises the viscosity of the bigel to between 30,000-150,000 cP (30-150 Pa·

s), and preferably between 80,000-140,000 cP (80-140 Pa·

s), measured using a Lamy VRM-08 with an MS DIN 1.3 module at 23°

C.

27. A method according to claim 1 wherein the high flow and low shear mixing is conducted using a combination of a planetary mixer at about 40-45 rpm and a Silverson type mixer at about 1500 rpm.

28. A method according to claim 1 wherein the high flow and low shear mixing is conducted using a turbine or Ystral®

mixer.

29. A method according to claim 1 wherein adjusting in step (d) is conducted under a vacuum.

30. A method according to claim 1 wherein an emulsifying agent is not added.

31. A method according to claim 1 further comprising the step of adding at least one preservative selected from sodium methylparaben, sodium propylparaben and sorbic acid.

32. A method according to claim 1 further comprising the step of adding at least one active pharmaceutical ingredient (API).

33. A method according claim 32 wherein the at least one API is selected from hormones, antimicrobial agents, allergens, vaccines, dermatologically active ingredients, cancer chemotherapeutic agents, anti-inflammatory agents, wound repair agents, analgesics, local anesthetics and anti-itch agents.

34. A method according claim 33 wherein the at least one API is a hormone selected from testosterone, progesterone and oestradiol.

35. A method according claim 34 wherein both testosterone and progesterone, or both testosterone and oestradiol, or both progesterone and oestradiol, are added.

36. A method according to claim 33 wherein the at least one anti-microbial agent is selected from antibacterial agents, antifungal agents and antiviral agents.

37. A method according to claim 1 further comprising the step of adding at least one further component selected from texture agents, antioxidants, dyes, or fragrances, moisturisers, sunscreens, anti-free-radical agents and skin regenerator agents.

38. A method according to claim 37 wherein the least one antioxidant is selected from butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT).

39. A method according to claim 1 wherein the bigel is packaged and presented for use in medicine.

40. A method according to claim 1 wherein the bigel is packaged and presented for cosmetic use.

41. A bigel obtainable by the method of claim 1.

42. A method of producing a bigel from an oleogel and an aqueous gel, characterised in that after the oleogel and the aqueous gel have been mixed together, the pH of the mixture is adjusted under high flow and low shear stirring to obtain a bigel having a desired viscosity.

43. A composition comprising:

at least one active agent selected from steroid hormones, glucosteroids and antimicrobial agents, each at 0.1-5% by weight;

a carbomer at 0.4-2% by weight;

caprylic/capric triglycerides at 10-30% by weight;

propylene glycol laurate, ethylcellulose and propylene glycol isostearate, at 1-10% by weight; and

water.

44. A composition according to claim 43 wherein the steroid hormone is selected from testosterone, progesterone and oestradiol.

45. A composition according to claim 44 comprising testosterone and progesterone, testosterone and oestradiol, or progesterone and oestradiol.

46. A composition according to claim 43 wherein the glucosteroid is selected from cortisol, hydrocortisone, cortisone acetate, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, beclomethasone, fludrocortisone acetate, deoxycorticosterone acetate and aldosterone.

47. A composition according to claim 43 wherein the antimicrobial agent is selected from antibacterial agents, antifungal agents and antiviral agents.

48. A composition according to claim 43 wherein the steroid hormone is a contraceptive hormone selected from progestogen, norethisterone, dydrogesterone, levonorgestrel, medroxyprogesterone, norgestrel, tinolone, dydrogesterone, desogestrone, drospirenone, gestodene, levonorgestrel, norelgestromin and norethisterone.

49. A composition according to claim 43 wherein each of the at least one active agents is present, independently, at about 0.5-2% by weight.

50. A composition according to claim 43 wherein the ethylcellulose, propylene glycol isostearate and propylene glycol laurate are present in relative proportions of about 2-10:

2-10;

80-96, respectively.

51. A composition according to claim 43 and having a pH of between 4-7.

52. A composition according to claim 43 further comprising any one or more of:

sorbic acid at between 0.05-0.4% by weight;

sodium methylparaben at between 0.05-0.4% by weight;

sodium propylparaben at between 0.05-0.4% by weight;

ethanol at between 1-10% by weight;

BHA at between 0.05-0.4% by weight; and

BHT at between 0.05-0.4% by weight.

53. A composition according to claim 43 that is a bigel.

54. A medicine comprising the composition according to claim 43.