Use of a hydrophilic matrix comprising a polyacrylic acid derivative, a cellulose ether and a disintegrant in the manufacture of a medicament for treating female genital disorders.

• US 20110091555A1
• Filed: 07/21/2007
• Published: 04/21/2011
• Est. Priority Date: 06/29/2006
• Status: Active Grant

• Current Assignee: Polichem, SA (Grupo Corporativo Landon SL)
• Original Assignee: Polichem, SA (Grupo Corporativo Landon SL)
• Inventors: Mailland, Federico, De Luigi Bruschi, Stefano
• Granted Patent: US 8,865,201 B2
• Time in Patent Office: Days
• US Class Current: 424/487
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 9/0039 Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis

Abstract

A hydrophilic matrix is disclosed which comprises:

a) at least one polyacrylic acid derivative in preferred amounts of 0.5-40%,
b) at least one cellulose ether in preferred amounts of 30-90% and
c) at least one disintegrant in preferred amounts of 2-50%,
with respect to the weight of the matrix.

This matrix is used in combination with at least one pharmaceutically acceptable active principle for manufacturing solid bioadhesive controlled release formulations for the treatment of vaginal disorders, such as vulvovaginal candidiasis, bacterial vaginosis or trichomoniasis.

According to a preferred embodiment, the matrix is used in amounts of about 5-60% and the active principle in amounts of about 2-70%, with respect to the weight of the formulation.

Claims

1-29. -29. (canceled)

30. A method for the treatment of female genital disorders in a patient in need of such a treatment, which comprises administering to the patient a formulation containing a hydrophilic matrix, said hydrophilic matrix comprising:

a) at least one polyacrylic acid derivative in amounts of 0.5-40% with respect to the weight of the matrix;

b) at least one cellulose ether; and

c) at least one disintegrant selected from modified celluloses, including cross-linked sodium carboxymethylcellulose, cross-linked polyvinylpyrrolidone, including crospovidone, natural starches, including maize starch, potato starch, directly compressible starches, modified starches, including carboxymethylstarches and sodium starch glycolate, starch derivatives including amylose, alginic acid and sodium alginate, and microcrystalline cellulose;

and at least one pharmaceutically acceptable active principle.

31. The method of claim 30, wherein the at least one disintegrant is cross-linked sodium carboxymethylcellulose.

32. The method of claim 30, wherein the at least one polyacrylic acid derivative is present in amounts of 2-40%, the at least one cellulose ether is present in amounts of 30-90% and the at least one disintegrant is present in amounts of 2-50%, with respect to the weight of the matrix.

33. The method of claim 32, wherein the at least one polyacrylic acid derivative is present in amounts of 2-30%, the at least one cellulose ether is present in amounts of 30-90% and the at least one disintegrant is present in amounts of 2-50%, with respect to the weight of the matrix.

34. The method of claim 30, wherein the at least one polyacrylic acid derivative is present in amounts of 1-20%, the at least one cellulose ether is present in amounts of 40-80% and the at least one disintegrant is present in amounts of 5-40%, with respect to the weight of the matrix.

35. The method of claim 30, wherein the at least one polyacrylic acid derivative is polyacrylic acid cross-linked with polyalkenyl ethers of sugars or polyalcohols.

36. The method of claim 35, wherein the at least one polyacrylic acid derivative is carbomer.

37. The method of claim 30, wherein the at least one polyacrylic acid derivative is a polyacrylic acid cross-linked with divinylglycol.

38. The method of claim 37, wherein the at least one polyacrylic acid derivative is polycarbophil.

39. The method of claim 30, wherein the at least one cellulose ether is selected from hydroxyalkylcellulose, alkylcellulose, carboxymethylcellulose and salts thereof.

40. The method of claim 30, wherein the at least one cellulose ether is a hydroxyalkylcellulose selected from hydroxypropylmethylcellulose, hydroxylpropylcellulose and hydroxyethylcellulose and/or an alkylcellulose selected from methylcellulose and ethylcellulose.

41. The method of claim 30, wherein the formulation is solid.

42. The method of claim 41, wherein the matrix of the solid formulation is present in amounts of about 5-60%, and the at least one active principle is present in amounts of about 2-70%, with respect to the weight of the formulation.

43. The method of claim 42, wherein the matrix is present in amounts of about 20-40%, and the at least one active principle is present in amounts of about 5-50%, with respect to the weight of the formulation.

44. The method of claim 41, wherein the formulation further comprises pharmaceutically acceptable fillers, excipients and/or adjuvants.

45. The method of claim 41, wherein the at least one active principle is selected from antimycotic, antibiotic, antiviral, antimicrobial or chemotherapeutic agents and hormones.

46. The method of claim 45, wherein the antimycotic agent is selected from hydroxy-2-pyridone compounds, imidazole derivatives, polyene derivatives, allylamine derivatives, triazole derivatives, morpholine derivatives, griseofulvin compounds, acidic compounds, tolnaphtate, flucytosine and salts thereof.

47. The method of claim 45, wherein the antimycotic agent is ciclopirox or ciclopirox olamine.

48. The method of claim 45, wherein the antibiotic or other antimicrobial agent is selected from aminoglycosides, tetracyclines, macrolides, quinolones, sulfonamides alone or combined with diaminopyridines, penicilline compounds, cephalosporins and other β

-lactam antibiotics, lincosamides, antiprotozoarians, antibacterials, antiseptics and salts thereof.

49. The method of claim 45, wherein the antibiotic is selected from nifuratel, metronidazole, tinidazole and clindamycin.

50. The method according to claim 45, wherein the antiviral agent is selected from idoxuridine, acyclovir, penciclovir, podophyllotoxin and imiquimod.

51. The method of claim 45, wherein the hormone is selected from oestradiol, ethinyloestradiol, estriol, promestriene, hydroxyprogesterone, progesterone, medroxyprogesterone, dihydrogesterone, nomegestrol, noretisterone, tibolone, testosterone, prasterone, mesterolone and any phytoestrogen.

52. The method of claim 44, wherein the excipient is selected from ascorbic acid, lactic acid and salts thereof.

53. The method of claim 41, wherein the solid formulation is a tablet.

54. The method of claim 53, wherein the solid formulation is a bioadhesive tablet.

55. The method according to claim 41, wherein the solid formulation is a controlled release formulation.

56. The method of claim 41, wherein said solid formulation is administered in the vaginal cavity.

57. The method of claim 30, wherein the female genital disorder(s) is a cervical and/or vaginal infection caused by fungi, bacteria, protozoa or viruses.

58. The method of claim 30, wherein the female genital disorder(s) is genital hypotrophy, genital atrophy, genital loss of elasticity, and/or vaginal dryness.