Unit galenical formulation for local hormonotherapy of vaginal dryness

• US 6,060,077 A
• Filed: 06/05/1998
• Issued: 05/09/2000
• Est. Priority Date: 10/05/1995
• Status: Expired due to Fees

• Current Assignee: Laboratoire Innothera Societe Anonyme
• Original Assignee: Laboratoire Innothera Societe Anonyme
• Inventors: Meignant, Catherine
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/051,242
• Time in Patent Office: 704 Days
• Field of Search: 424/434, 424/435
• US Class Current: 424/434
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/801 Drug
• CPC Class Codes: Y10S 977/906 Drug delivery
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition

Abstract

A galenical formulation is intended for local, essentially non systemic, treatment of vaginal dryness, in particular in the menopausal woman. It comprises a free natural estrogen, in particular a micronized or vectorized estrogen, selected from 17β-estradiol and its salts in solution or in suspension in a lipophilic agent, with an estrogen content which corresponds to an equivalent unit dose of at most 15 μg, preferably less than 10 μg, of 17β-estradiol, a hydrophilic gel-forming bioadhesive agent, a gelling agent for the lipophilic agent and a hydrodispersible agent. The soft capsule form comprises a hard or soft outer envelope containing gelatin and glycerine and a non aqueous liquid or semi-liquid inner phase containing the lipophilic agent with the estrogen in solution or in suspension, the bioadhesive agent and the hydrophilic gelling agent for the lipophilic agent. The slow release vaginal suppository comprises a non aqueous hard or semi-soft solid homogeneous phase containing the lipophilic agent with the estrogen in solution or in suspension, the hydrophilic bioadhesive gel-forming agent, the gelling agent for the lipophilic agent and the hydrodispersible agent.

Claims

1. A pharmaceutical medicament for local, essentially non-systemic, treatment of vaginal dryness, in particular in the menopausal woman, characterized by a unit galenical formulation comprising a natural estrogen selected from the group consisting of 17β

-estradiol and its salts and its derivatives in solution or in suspension in a lipophilic agent, with an estrogen content which corresponds to an equivalent unit dose of at most 15 μ

g, preferably less than 10 μ

g, of 17β

-estradiol, a hydrophilic gel-forming bioadhesive agent, a gelling agent for the lipophilic agent, and a hydrodispersible agent.

2. The medicament of claim 1, in which the estrogen is present in its free form.

3. The medicament of claim 1, in which the estrogen is present in its vectorized form.

4. The medicament of claim 3, in which the estrogen is vectorized by encapsulation in nanoparticle type vectors.

5. The medicament of claim 4, in which the estrogen is vectorized by encapsulation in particulate supramolecular biovector type vectors.

6. The medicament of claim 1, in capsule form comprising a hard or soft solid outer envelope containing gelatin and a non aqueous liquid or semi-liquid inner phase containing the lipophilic agent with the estrogen in solution or in suspension, the hydrophilic gel-forming bioadhesive agent, the gelling agent for the lipophilic agent and the hydrodispersible agent.

7. The medicament of claim 6, in the form of a soft capsule, in which the outer envelope contains glycerine.

8. The medicament of claim 6, in which the lipophilic agent is selected from liquid triglycerides.

9. The medicament of claim 6, in which the hydrophilic gel-forming bioadhesive agent is selected from the group consisting of carboxyvinylic acids, hydroxypropylcellulose, carboxymethylcellulose, gelatin, xanthane gum, guar gum, aluminum silicate and mixtures thereof.

10. The medicament of claim 6, in which the gelling agent for the lipophilic agent is hydrophobic colloidal silica.

11. The medicament of claim 6, in which the hydrodispersible agent is selected from the group consisting of polyoxyethylene glycols, polyoxyethylene glycol 7-glyceryl-cocoate and mixtures thereof.

12. The medicament of claim 6, in which the composition of the inner phase is:

space="preserve" listing-type="tabular">______________________________________ Free or vectorized 17β

-estradiol 2.5 μ

g to 15 μ

g Hydroxypropylcellulose 120 mg Hydrophobic colloidal silica 50 mg to 80 mg Polyoxyethylene glycol 7-glyceryl-cocoate 400 mg Liquid triglycerides q.s. 1600 mg. ______________________________________

13. The medicament of claim 1, in the form of a slow release vaginal suppository comprising a non aqueous hard or semi-soft solid homogeneous phase containing the lipophilic agent with the estrogen in solution or in suspension, the hydrophilic gel-forming bioadhesive agent, the gelling agent for the lipophilic agent and the hydrodispersible agent.

14. The medicament of claim 13, in which the lipophilic agent is selected from solid triglycerides with a melting point of about 35°

C., carnauba wax, cocoa butter and mixtures thereof.

15. The medicament of claim 13, in which the hydrophilic gel-forming bioadhesive agent is selected from the group consisting of carboxyvinylic acids, hydroxypropylcellulose, carboxymethylcellulose, gelatin, xanthane gum, guar gum, aluminum silicate and mixtures thereof.

16. The medicament of claim 3, in which the gelling agent for the lipophilic agent is hydrophobic colloidal silica.

17. The medicament of claim 13, wherein the gel comprises a hydrophilic emollient component selected from the group consisting of glycerine, propylene glycols, polyoxyethylene glycols, and mixtures thereof.

18. The medicament of claim 13, in which the composition is:

space="preserve" listing-type="tabular">______________________________________ Free or vectorized 17β

-estradiol 2.5 μ

g to 15 μ

g Hydroxypropylcellulose 80 mg Hydrophobic colloidal silica 5 mg to 60 mg Polyoxyethylene glycol 50 mg to 200 mg Carboxyvinylic acid 8 mg Solid triglycerides q.s. 1600 mg. ______________________________________

19. The medicament of claim 2, in which the estrogen is micronized.

20. The medicament of claim 3, in which the estrogen is micronized.