Stable gel mixture in the form of a mixture of oleogel and aqueous gel, process for its preparation, pharmaceutical and cosmetic compositions comprising it, and use of the pharmaceutical compositions

• US 6,187,323 B1
• Filed: 12/03/1998
• Issued: 02/13/2001
• Est. Priority Date: 06/03/1998
• Status: Expired due to Term

• Current Assignee: Aptys Pharmaceuticals SAS
• Original Assignee: Zentrx, Inc.
• Inventors: Aiache, Jean-Marc, Gauthier, Pascale
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Ware, Todd D.
• Application Number:
  US09/204,089
• Time in Patent Office: 803 Days
• Field of Search: 424/401, 424/78.02, 424/443, 424/447, 424/449, 514/944, 514/969
• US Class Current: 424/401
• 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 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• 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 31/585 containing lactone rings, e.g. oxandrolone, bufalin
• CPC Class Codes: A61K 8/042 Gels
• 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: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C08J 3/075 Macromolecular gels

Abstract

The present invention relates to a stable gel mixture, having a substantially uniform appearance, which stable gel mixture comprises at least one oleogel and of at least one aqueous gel, the oleogel comprising at least one oily agent gelled with at least one cellulose polymer. The present invention also relates to a pharmaceutical composition comprising this gel, to the use of this pharmaceutical composition as a reservoir for active ingredients in a transdermal release system, as well as to a cosmetic composition comprising this gel. This gel has remarkable stability and a fresh and pleasant feel.

Claims

1. A stable gel mixture, that has a substantially uniform appearance and that comprises at least one oleogel and at least one aqueous gel, the oleogel comprising at least one oily agent gelled with at least one cellulose polymer.

2. The stable gel mixture according to claim 1, wherein the cellulose polymer is an ethylcellulose, a non-sodium containing carboxymethylcellulose, or a mixture thereof.

3. The stable gel mixture according to claim 1, wherein the oily agent is a mono-, di- and triglycerides of synthetic, semisynthetic or natural origin, or a mixtures thereof.

4. The stable gel mixture according to claim 3, wherein the oily agent is selected from the group consisting of a synthetic di- or triglyceride;

a propylene glycol isostearate;

a mixture of polyoxyethylenated oleic glycerides and an oil of plant origin.

5. The stable gel mixture according to claim 1, wherein the cellulose polymer is an ethyl-cellulose, present in a proportion of between about 1% and about 10% by weight relative to the total weight of the oleogel;

wherein the oily agent comprises a mixture of polyoxyethylenated oleic glycerides, present in a proportion of between about 5% and about 90% by weight, relative to the total weight of the oleogel; and

wherein the ratio of the weight of oleogel to the weight of aqueous gel is between about 10;

90 and about 90;

10.

6. The stable gel mixture according to claim 5, wherein the oleogel further comprises propylene glycol isostearate, in a proportion of between about 5% and about 90% by weight, relative to the total weight of the oleogel.

7. The stable gel mixture according to claim 1, wherein the aqueous gel comprises at least one gelling agent selected from the group consisting of carbomers, poloxamers, sodium carboxymethylcellulose and mixtures thereof, wherein the gelling agent is present in a proportion of between about 0.1% and about 10% by weight, relative to the total weight of the aqueous gel, and wherein the ratio of the weight of oleogel to the weight of aqueous gel is between about 10:

90 and about 90;

10.

8. The stable gel mixture according to claim 7, wherein the gelling agent is a carbomer, present in a proportion of between about 0.1% and about 5% by weight, relative to the total weight of the aqueous gel.

9. A process for the preparation of the stable gel mixture according to claim 1, comprising the steps of:

a) forming an oleogel, the viscosity of the oleogel formed being adjusted, where necessary by heating, to a value of between about 20 and about 40 Pa.s;

b) forming an aqueous gel, the viscosity of the aqueous gel formed being adjusted, where necessary by heating, to a value of between about 10 and about 30 Pa.s; and

c) incorporating the oleogel formed into the aqueous gel or vice versa, with non-shear stirring, until a stable gel mixture of substantially uniform appearance is obtained.

10. A stable pharmaceutical composition, which can be administered topically, orally or parenterally, comprising a stable gel mixture according to claim 1, and at least one pharmaceutically active ingredient in at least one of the oleogels or the aqueous gels.

11. The pharmaceutical composition according to claim 10, wherein the oleogel comprises at least a first active ingredient and the aqueous gel comprises at least a second active ingredient, wherein the first and second active ingredients are incompatible or compatible with each other.

12. The pharmaceutical composition according to claim 10, wherein the oleogel comprises β

-oestradiol, in a proportion of between 0.1% and about 5% by weight, relative to the total weight of the oleogel;

wherein the aqueous gel comprises progesterone, in a proportion of between about 1% and about 6% by weight, relative to the total weight of the aqueous gel; and

wherein the ratio of the weight of oleogel to the weight of aqueous gel is between about 10;

90 and about 90;

10.

13. The pharmaceutical composition according to claim 10, wherein the oleogel comprises testosterone, in a proportion of between 0.1% and 6% by weight, relative to the total weight of the oleogel;

wherein the aqueous gel comprises testosterone, in a proportion of between about 1% and about 10% by weight, relative to the total weight of the aqueous gel; and

wherein the ratio of the weight of oleogel to the weight of aqueous gel is between about 10;

90 and about 90;

10.

14. The pharmaceutical composition according to claim 10, wherein the active ingredient is a sulphur-containing active ingredient.

15. The composition according to claim 14, wherein the sulphur-containing active ingredient is spironolactone present in the oleogel in a proportion of between about 0.5% and about 10% by weight, relative to the total weight of the oleogel, and wherein the ratio of the weight of oleogel to the weight of aqueous gel is between about 10:

90 and about 90;

10.

16. A method for preparing a transdermal releasing composition comprising adding at least one active ingredient to the pharmaceutical composition according to claim 10, wherein the pharmaceutical composition according to claim 10 serves as an active ingredient reservoir in a transdermal release system.

17. A stable cosmetic composition, comprising the stable gel mixture according to claim 1, wherein at least one of the oleogels or the aqueous gels comprise at least one cosmetically active ingredient.

18. The cosmetic composition according to claim 17, wherein the cosmetically active ingredient is a body-care oil.