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EP-3804695-B1 - A VAGINAL CONTRACEPTIVE COMPOSITION FOR REINFORCEMENT OF MUCUS BARRIER PROPERTIES

EP3804695B1EP 3804695 B1EP3804695 B1EP 3804695B1EP-3804695-B1

Inventors

  • CROUZIER, THOMAS
  • Schimpf, Ulrike

Dates

Publication Date
20260506
Application Date
20191011

Claims (10)

  1. A vaginal contraceptive composition comprising one or more active ingredients and a physiological acceptable gelling agent, wherein at least one of the one or more active ingredients is a mucoadhesive polymer, wherein said mucoadhesive polymer has a molecular weight (M w ) between 20.000 Da and 100.000 Da, wherein said mucoadhesive polymer consists of a plurality of monomer units linked to each other via ether bonds, ester bonds, amide bonds, or combinations hereof, wherein the monomer units are a combination of D-glucosamine and N-acetyl-D-glucosamine, and wherein at least 50% of the monomer units comprise at least one amino group.
  2. The vaginal contraceptive composition according to claim 1, wherein the vaginal contraceptive composition is not a foam.
  3. The vaginal contraceptive composition according to any preceding claim, wherein the mucoadhesive polymer has a molecular weight between 20.000 Da and 90.000 Da, such as between 30.000 Da and 75.000 Da, such as between 30.000 Da and 60.000 Da, such as between 30.000 Da and 50.000 Da, such as between 30.000 Da and 40.000 Da.
  4. The vaginal contraceptive composition according to any preceding claim, wherein at least 55% of the monomer units comprise at least one amino group, such as at least 60% of the monomer units comprise at least one amino group, such as at least 65% of the monomer units comprise at least one amino group, such as at least 70% of the monomer units comprise at least one amino group.
  5. The vaginal contraceptive composition according to any preceding claim, wherein the at least one amino group is a primary amine.
  6. The vaginal contraceptive composition according to any preceding claim, wherein at least 50% is D-glucosamine and 50% or less is N-acetyl-D-glucosamine, such as between 50% and 100% is D-glucosamine and between 0% and 50% is N-acetyl-D-glucosamine, such as at least 65% is D-glucosamine and 35% or less is N-acetyl-D-glucosamine, such as between 65% and 100% is D-glucosamine and between 0% and 35% is N-acetyl-D-glucosamine.
  7. The vaginal contraceptive composition according to any preceding claim, wherein the physiological acceptable gelling agent is selected from hydroxyethyl cellulose (HEC), glycerol, hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose, guar gum, or combinations hereof.
  8. The vaginal contraceptive composition according to any preceding claim, wherein the mucoadhesive polymer is in a concentration of between 0.05 wt.% and 10.0 wt.% of the total weight of the vaginal contraceptive composition.
  9. The vaginal contraceptive composition according to any preceding claim, wherein pH of the composition is between 2.0 and 7.0, such as between 2.5 and 6.5, such as between 3.0 and 6.0.
  10. Use of a vaginal contraceptive composition according to any of claims 1-9 as a contraceptive agent.

Description

Technical Field The invention relates to a vaginal contraceptive composition comprising one or more active ingredients and a physiological acceptable gelling agent, wherein at least one of the one or more active ingredients is a mucoadhesive polymer. The invention also relates to uses of such a vaginal contraceptive composition in therapy or contraception. The mucoadhesive polymer can cross-link the mucus layer without aggregating the mucus. Background art The citation and incorporation of patent documents herein is done for convenience only and does not reflect any view of the validity, patentability, and/or enforceability of such patent documents. There is a rapidly growing number of women that are unhappy with hormonal contraceptives but cannot find alternatives that are both convenient (no implantations, easy to use, flexible to use) and effective (over 90% efficacy in a typical use case). Indeed, 125 million couples in Europe and the US use birth control and hormonal contraceptives (pill, patch, implant, ring, etc.) are by far the most used birth control method. However, an increasing awareness of the side effects caused by hormones is upending the market for contraceptives. There are now robust evidence for side effects of hormonal contraceptives. Three studies including between 0.5 million and 1.8 million women show that the use of hormonal contraceptives increases women's rate of taking antidepressants by 23% and for teens the rate nearly doubles (Charlotte Wessel Skovlund, Lina Steinrud Mørch, Lars Vedel Kessing, and Øjvind Lidegaard. 2016. "Association of Hormonal Contraception With Depression." JAMA Psychiatry 73 (11): 1154-62), increases women's rate of suicide attempt by 197% and the suicide rate by 308% (Charlotte Wessel Skovlund, Lina Steinrud Mørch, Lars Vedel Kessing, Theis Lange, and Øjvind Lidegaard. 2017. "Association of Hormonal Contraception With Suicide Attempts and Suicides." The American Journal of Psychiatry, November) and increases the risk of developing breast cancer by 9% when used for less than a year and up to 38% when used for 10 years (Lina S. Mørch, Charlotte W. Skovlund, Philip C. Hannaford, Lisa Iversen, Shona Fielding, and Øjvind Lidegaard. 2017. "Contemporary Hormonal Contraception and the Risk of Breast Cancer." The New England Journal of Medicine 377 (23): 2228-39). Many women now wish to move away from hormonal contraception, but they are unable to find suitable alternatives. The current alternatives are either inconvenient (condoms, diaphragms) or invasive (copper and hormone eluting implants) and can be poorly effective in actual use case (for instance condoms are only 85% effective on average). There are over 400 square meters of epithelial surfaces hidden within the body of a human being, including the lung, gastrointestinal tract, and the female reproductive tract. The wet epithelial surfaces rely on a mucus gel for protection from dehydration, shear stress, and infections. Besides water, mucus mainly contains mucin biopolymers mixed with proteins, lipids, and salts. Mucins are large glycoproteins, which consist of an extended central protein core densely conjugated with oligosaccharides that can account for up to 50% of the molecule's molecular weight. Mucins have a central role in the protective function, creating a barrier, which serves as a size exclusion and affinity-based selective filter, preventing many deleterious molecules from reaching the epithelial surface. Mucoadhesive polymers have been used for drug delivery due to their adhesive properties. For instance, they have been used to deliver drugs to inflammation sites. Mucoadhesive polymers are typically assembled into materials or a gel alongside a drug, the intent being to concentrate the drug at the surface of the mucus layer and improve drug delivery. WO2004069230 relates to pharmaceutical compositions containing a physiologically active agent, i.e. a drug, and a release sustaining or mucoadhesive agent e.g. chitosan, which serves to prolong the release of the active agent from the composition. Another use for chitosan is in female contraception. One example of such may be found in CN102895256, which relates to chitosan gel foaming agent suitable for a female contraception and fungicidal effect and a preparation method thereof, and belongs to the technical field of foaming agent production. According to this disclosure, chitosan molecules are trapped in a solid foam matrix in association with polyacrylic acid, which physically prevents sperm passage. Additionally, the chitosan has a molecular weight distribution of 2000-5000 Da, a deacetylation degree above 95%, and a concentration of 5-10 wt.%, whereas the polyacrylic acid is in a concentration of 1-3 wt.%. Another example of chitosan for female contraception may be found in WO2018185321, which relates to a mucoadhesive polymer, more specifically chitosan, which can cross-link the mucus layer without aggregating the mucus. The chitosan consisting