Ph-dependent vaginal compositions and methods of treatment of vaginal disorders

Abstract

The present invention provides a pH dependent vaginal composition delivering a therapeutically effective amount of at least one active essentially at a pH above 4.5. The composition provides a diagnostic visual pH indication of the presence of vulvovaginitis at pH above 4.5. In the absence of such indication, the treatment may be discontinued. Another visual signal is the retrieval of the unchanged composition, which also points to a normal pH at or below 4.5 and absence of vulvovaginitis.

What is claimed is: 
     
         1 . A method of treatment of vaginal disorders associated with a vaginal pH reading higher than 4.5, comprising:
 administering to a patient in need thereof a vaginal composition comprising a therapeutically effective amount of at least one active agent and a pH-dependent polymer allowing the active agent delivery at pH higher than 4.5, and optionally a pH indicator; and   retrieving the vaginal composition, wherein retrieval of an unchanged composition, a visual indication of a pH below 4.5 or combination thereof is a visual signal of the absence of vaginal disorders and a signal to discontinue treatment.   
     
     
         2 . The method of treatment of  claim 1 , wherein the vaginal disorder is selected from vulvovaginitis, bacterial vaginosis, trichomoniasis, yeast infection, candida, atrophic vaginitis, viruses, parasites, allergens and sexually transmitted infections. 
     
     
         3 . The method of treatment of  claim 1 , wherein the vaginal disorder is selected from bacterial vaginosis and vulvovaginitis. 
     
     
         4 . The method of treatment of  claim 1 , wherein the at least one active agent is selected from the group consisting of butoconazole, clotrimazole, miconazole, terconazole, tioconazole, clindamycin, fluconazole, metronidazole, nystatin, estrogens, progestogens, and combinations thereof. 
     
     
         5 . The method of treatment of  claim 1 , wherein the at least one active agent is metronidazole. 
     
     
         6 . The method of treatment of  claim 1 , comprising administering a therapeutically effective amount of the pH-dependent vaginal composition to the subject one to three times per day, for one to seven days. 
     
     
         7 . The method of treatment of  claim 1 , wherein the composition is a pH-dependent vaginal capsule, a pH-dependent vaginal insert, a pH-dependent suppository, a pH-dependent cream, a pH-dependent gel, a pH-dependent foam, or a pH-dependent suspension. 
     
     
         8 . The method of treatment of  claim 7 , wherein the composition is a capsule and wherein the capsule wall is configured to disintegrate at pH values greater than pH 4.5 and is water insoluble at a pH of 4.5 and below. 
     
     
         9 . The method of treatment of  claim 7 , wherein the composition is a capsule comprising a pH-dependent polymer coating and, wherein upon administration of the composition, the pH-dependent polymer coating disintegrates at pH 4.5 to deliver the at least one active agent. 
     
     
         10 . The method of treatment of  claim 7 , wherein the composition is configured to deliver the at least one active in a sustained release manner. 
     
     
         11 . The method of treatment of  claim 1 , wherein the vaginal composition is formulated as a matrix comprising a pH-dependent polymer configured to deliver the at least one active agent at pH values greater than 4.5. 
     
     
         12 . The method of treatment of  claim 9 , wherein the pH-dependent polymer coating is configured to disintegrate at pH values greater than pH 4.5, is water insoluble at a pH of 4.5 and below, and is water soluble at a pH greater than 4.5. 
     
     
         13 . The method of treatment of  claim 9 , wherein the pH-dependent polymer coating is configured to disintegrate at pH values greater than pH 4.5 and is water soluble at a pH greater than 5. 
     
     
         14 . The method of treatment of  claim 9 , wherein the pH-dependent polymer coating is configured to disintegrate at pH values greater than pH 4.5 and is water soluble at a pH greater than 5.5. 
     
     
         15 . The method of treatment of  claim 9 , wherein the pH-dependent polymer coating is water soluble at a pH greater than 6. 
     
     
         16 . The method of treatment of  claim 7 , wherein the pH dependent vaginal composition is contained in a pouch configured to retrieve the composition, wherein the pouch comprises a tape configured to retrieve the pouch. 
     
     
         17 . The method of treatment of  claim 16 , wherein the tape is impregnated with a pH indicator to provide a visual indication of the vaginal pH, wherein the visual indication is indicative of the presence of a vaginal disorder at pH above 4.5 or of a normal vaginal pH at or below 4.5. 
     
     
         18 . The method of  claim 1  wherein the composition is a matrix, a capsule or a suppository. 
     
     
         19 . A method of treatment of vaginal disorders associated with a vaginal pH reading higher than 4.5, comprising:
 administering to a patient in need thereof a vaginal composition comprising a therapeutically effective amount of at least one active agent and a pH-dependent polymer coating, wherein the active agent is delivered at pH higher than 4.5, wherein the pH-dependent polymer coating is configured to disintegrate at pH values greater than pH 4.5, is water insoluble at a pH of 4.5 and below, and is water soluble at a pH greater than 4.5; and   retrieving the vaginal composition, wherein retrieval of an unchanged composition is a visual signal of the absence of vaginal disorders and a signal to discontinue treatment.   
     
     
         20 . The method of  claim 19  wherein the composition is a matrix, a capsule or a suppository.