Semi-solid compositions and pharmaceutical products

Abstract

This invention relates to semi-solid compositions and semi-solid pharmaceutical products for use in the photodynamic treatment (PDT) of cancer, pre-cancerous conditions and non-cancerous conditions in the female reproductive system, the anus and the penis, preferably for use in PDT of endometrial, cervical, vulvar, vaginal, anal and penile dysplasia and HPV infections of the uterus, cervix, the vulva, the vagina, the anus and the penis. The semi-solid compositions and pharmaceutical products comprise an active ingredient which is 5-aminolevulinic acid (5-ALA) or a precursor or derivative of 5-ALA or pharmaceutically acceptable salts thereof. The invention relates further to methods of PDT of cancer, pre-cancerous conditions and non-cancerous conditions in the female reproductive system, the anus and the penis, wherein said semi-solid compositions and pharmaceutical products are used.

1 . Semi-solid pharmaceutical product for use in the photodynamic treatment of cancer, pre-cancerous conditions and non-cancerous conditions in the female reproductive system, the anus and the penis comprising
 a) an active ingredient selected from 5-ALA, a precursor of 5-ALA or a derivative of 5-ALA and pharmaceutically acceptable salts thereof;   b) one or more triglycerides; and   c) optionally one or more viscosity enhancers.   
     
     
         2 . Semi-solid pharmaceutical product according to  claim 1  wherein said active ingredient is a derivative of 5-ALA, preferably a 5-ALA ester or a pharmaceutically acceptable salt thereof. 
     
     
         3 . Semi-solid pharmaceutical product according to  claim 1  wherein said active ingredient is a compound of formula I or a pharmaceutically acceptable salt thereof
   R 2   2 N—CH 2 COCH 2 —CH 2 CO—OR 1   (I)
 
 wherein 
 R 1  represents a substituted or unsubstituted alkyl group; and 
 R 2  each independently represents a hydrogen atom or a group R 1 . 
 
     
     
         4 . Semi-solid pharmaceutical product according to  claim 1  wherein the one or more triglycerides are triglycerides of glycerol and 3 identical or different C 2 -C 22  fatty acids, more preferably 3 identical or different C 4 -C 18  fatty acids, even more preferably 3 identical or different C 6 -C 18  fatty acids and most preferably 3 identical or different C 6 -C 12  fatty acids. 
     
     
         5 . Semi-solid pharmaceutical product according to  claim 1  wherein the one or more triglycerides are liquid triglycerides and one or more viscosity enhancers are present. 
     
     
         6 . Semi-solid pharmaceutical product according to  claim 5  wherein the one or more viscosity enhancers are selected from cellulose and derivatives thereof, synthetic polymers, polyethylene glycols, vegetable gums, starch and starch derivatives, carrageenan, agar, gelatin, wax and waxy solids, preferably selected from a wax or a waxy solid, most preferably selected from a solid fatty alcohol or fatty acid. 
     
     
         7 . Semi-solid pharmaceutical product according to  claim 1  further comprising
 d) optionally one or more emulsifiers 
 e) optionally one or more mucoadhesive 
 f) optionally one or more pharmaceutically acceptable excipients other than b) and c), 
 g) optionally one or more surface penetration agents; and 
 h) optionally one or more chelating agents. 
 
     
     
         8 . Semi-solid pharmaceutical product according to  claim 1  wherein said semi-solid pharmaceutical product is water-free. 
     
     
         9 . Semi-solid pharmaceutical product according to  claim 1  contained in a drug delivery system, preferably contained in a drug delivery system selected from pessaries, diaphragms, caps, adhesive bandages or patches. 
     
     
         10 . Kit comprising a semi-solid pharmaceutical product according to  claim 1  and a drug delivery system, preferably a drug delivery system selected from pessaries, diaphragms, caps, adhesive bandages or patches. 
     
     
         11 . Semi-solid composition consisting of
 a) an active ingredient selected from 5-ALA, a precursor of 5-ALA or a derivative of 5-ALA and pharmaceutically acceptable salts thereof;   b) one or more triglycerides; and   c) optionally one or more viscosity enhancers.   
     
     
         12 . Semi-solid composition according to  claim 11 , wherein the active ingredient is a derivative of 5-ALA, preferably a 5-ALA ester or a pharmaceutically acceptable salt thereof, the one or more triglycerides is a liquid triglyceride, preferably selected from triglycerides of glycerol and 3 identical or different C 2 -C 22  fatty acids, more preferably 3 identical or different C 4 -C 18  fatty acids, even more preferably 3 identical or different C 6 -C 18  fatty acids and most preferably 3 identical or different C 6 -C 12  fatty acids and the one or more viscosity enhancers are present. 
     
     
         13 . Semi-solid composition according to  claim 12  wherein said one or more viscosity enhancers are selected from a wax or a waxy solid, most preferably selected from a solid fatty alcohol or fatty acid. 
     
     
         14 . Semi solid composition according to  claim 11  for use as a medicament. 
     
     
         15 . Semi-solid pharmaceutical product according to  claim 1  for use in the photodynamic treatment of cancer, pre-cancerous conditions and non-cancerous conditions in the female reproductive system, the anus and the penis, more preferably for use in photodynamic treatment of dysplasia and HPV infections in the female reproductive system, the anus and the penis, even more preferably endometrial, cervical, vaginal, vulvar, anal and penile dysplasia and HPV infections of the uterus, cervix, vagina, vulva, anus and penis.