# US 2014/0194448 A1 · Transvaginal phosphodiesterase inhibitors for infertility treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0194448 A1 - Document ID: US20140194448A1 - Status: Published application - Kind: A1 - Application number: 14/128,953 - Filed: 2012-06-20 - Published: 2014-07-10 - Earliest claimed: 2011-06-23 - Assignees: Prokrea Bcn, S.L. - Inventors: Maria Carmen Pardina Palleja; Miguel Angel Vaz-Romero Uña - Web page: https://patentgrep.com/patent/US20140194448A1 ## CPC - A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir - A61K 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil - A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline - A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to a new application of phosphodiesterase inhibitors for couple infertility treatment which forms an effective alternative to the invasive assisted reproductive techniques such as conjugal artificial insemination and which consists of the transvaginal administration of a phosphodiesterase inhibitor immediately before and/or after coitus. It also relates to dosage forms suitable for the intravaginal administration of phosphodiesterase inhibitors. ## Claims ### Claim 1 A phosphodiesterase inhibitor for use in the treatment of couples with infertility administered transvaginally. ### Claim 2 (depends on 1) The phosphodiesterase inhibitor for use according to claim 1, characterized in that it is selected from the group consisting of a phosphodiesterase 1 (PDE1) inhibitor, a phosphodiesterase 3 (PDE3) inhibitor, a phosphodiesterase 4 (PDE4) inhibitor and a non-selective phosphodiesterase inhibitor, and a combination thereof. ### Claim 3 (depends on 2) The phosphodiesterase inhibitor for use according to claim 2, characterized in that it is selected from the group consisting of pentoxifylline, rolipram, milrinone and ibudilast. ### Claim 4 (depends on 3) The phosphodiesterase inhibitor for use according to claim 3, characterized in that it is pentoxifylline. ### Claim 5 (depends on 1) The phosphodiesterase inhibitor for use according to claim 1, characterized in that the infertility is substantially caused by male infertility. ### Claim 6 (depends on 5) The phosphodiesterase inhibitor for use according to claim 5, characterized in that the male infertility is due to anomalies in semen characteristics. ### Claim 7 (depends on 6) The phosphodiesterase inhibitor for use according to claim 6, characterized in that the male infertility is due to asthenozoospermia. ### Claim 8 (depends on 1) The phosphodiesterase inhibitor for use according to claim 1, characterized in that the dose of the phosphodiesterase inhibitor is comprised between 200 mg and 800 mg in each administration. ### Claim 9 (depends on 1) The phosphodiesterase inhibitor for use according to claim 1, characterized in that the phosphodiesterase inhibitor is administered in combination with an ovulation-inducing drug. ### Claim 10 (depends on 1) The phosphodiesterase inhibitor for use according to claim 1, characterized in that the phosphodiesterase inhibitor is administered before and/or after coitus. ### Claim 11 (depends on 1) The phosphodiesterase inhibitor for use according to claim 1, characterized in that the treatment is applied as a complement to the artificial insemination technique. ### Claim 12 (depends on 1) The phosphodiesterase inhibitor for use according to claim 1, characterized in that it is administered in the form of a pharmaceutical composition comprising a phosphodiesterase inhibitor and at least one pharmaceutically acceptable excipient. ### Claim 13 (depends on 12) The phosphodiesterase inhibitor for use according to claim 12, characterized in that the pharmaceutical composition is in the form of an ovule, vaginal suppository, vaginal tablet, cream, ointment, paste, gel or foam. ### Claim 14 (depends on 13) The phosphodiesterase inhibitor for use according to claim 13, characterized in that the composition is in the form of gel, ointment or cream. ### Claim 15 (depends on 14) The phosphodiesterase inhibitor for use according to claim 14, characterized in that the composition is in the form of gel. ### Claim 16 A pharmaceutical composition in the form of hydrophilic gel for transvaginal administration comprising a phosphodiesterase inhibitor, a polyhydroxy alcohol, water, a carbomer and an alkaline agent. ### Claim 17 (depends on 16) The composition according to claim 16, characterized in that the phosphodiesterase inhibitor is selected from the group consisting of a phosphodiesterase 1 (PDE1) inhibitor, a phosphodiesterase 3 (PDE3) inhibitor, a phosphodiesterase 4 (PDE4) inhibitor and a non-selective phosphodiesterase inhibitor, and a combination thereof. ### Claim 18 (depends on 17) The composition according to claim 17, characterized in that the phosphodiesterase inhibitor is selected from the group consisting of pentoxifylline, rolipram, milrinone and ibudilast. ### Claim 19 (depends on 18) The composition according to claim 18, characterized in that the phosphodiesterase inhibitor is pentoxifylline. ### Claim 20 (depends on 16) The composition according to claim 16, characterized in that the polyhydroxy alcohol is selected from the group consisting of propylene glycol, dipropyleneglycol, glycerin, 1,2,6-hexanetriol, sorbitol, polyethylene glycol 100 (PEG100), polyethylene glycol 200 (PEG200), polyethylene glycol 300 (PEG300) and polyethylene glycol 400 (PEG400). ### Claim 21 (depends on 20) The composition according to claim 20, characterized in that the polyhydroxy alcohol is propylene glycol. ### Claim 22 (depends on 16) The composition according to claim 16, characterized in that the carbomer has a viscosity comprised between 25000 and 700000 mPa·s determined in an aqueous carbomer solution at 0.5% by weight/volume and at a pH value comprised between 6 and 11. ### Claim 23 (depends on 22) The composition according to claim 22, characterized in that the carbomer has a viscosity comprised between 40000 and 60000 mPa·s determined in an aqueous carbomer solution at 0.5% by weight/volume and at pH comprised between 6 and 11. ### Claim 24 (depends on 16) The composition according to claim 16, characterized in that the alkaline agent is selected from the group consisting of L-lysine, L-arginine, borax, potassium hydroxide, sodium hydroxide, ammonia, sodium bicarbonate, aminomethylpropanol , tetrahydroxypropylethylenediamine, tromethamine, ethoxylated cocoamine (cocamine PEG15), diisopropanolamine, triisopropanolamine, and triethanolamine. ### Claim 25 (depends on 24) The composition according to claim 24, characterized in that the alkaline agent is triethanolamine. ### Claim 26 (depends on 16) The composition according to claim 16, characterized in that the proportion of the phosphodiesterase inhibitor by weight is comprised between 2% and 10%. ### Claim 27 (depends on 26) The composition according to claim 26, characterized in that the composition comprises a phosphodiesterase inhibitor in a proportion by weight comprised between 2% and 10%, propylene glycol in a proportion by weight comprised between 2% and 15%, carbomer in a proportion by weight comprised between 0.5% and 2%, triethanolamine in a proportion by weight comprised between 0.1% and 1% and water in a proportion by weight comprised between 75% and 95%. ### Claim 28 (depends on 16) The composition according to claim 16, characterized in that the composition has a pH comprised between 5.5 and 7.5. ### Claim 29 (depends on 16) A kit characterized in that it includes the composition according to claim 16 and instructions for administrating same. ### Claim 30 (depends on 29) The kit according to claim 29, characterized in that it includes three single-doses of phosphodiesterase inhibitor between 200 mg and 800 mg in each of them.