Oral antimicrobial pharmaceutical compositions
View Patent ↗The present invention relates to oral pharmaceutical compositions with controlled and/or programmed release containing at least one active ingredient having antimicrobial and/or anti-infectious activity for the treatment of infections of the large intestine, in particular the colon.
1. A controlled release oral pharmaceutical composition comprising:
(1) a tablet core comprising a homogeneous structure comprising (a) rifamycin SV in an amount effective for the treatment of an infection of the colon, (b) at least one lipophilic substance having a melting point less than about 90° C, (c) at least one amphiphilic substance and (d) at least one hydrophilic substance; and
(2) a coating on said tablet core, said coating comprising a gastro-resistant substance, wherein said controlled release oral pharmaceutical composition releases said rifamycin SV substantially in the large intestine.
2. The controlled release oral pharmaceutical composition of claim 1 , wherein said controlled release oral pharmaceutical composition releases said rifamycin SV solely in the colon.
3. The controlled release oral pharmaceutical composition of claim 1 , wherein said rifamycin SV comprises rifamycin SV or a pharmaceutically acceptable salt thereof.
4. The controlled release oral pharmaceutical composition of claim 1 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution for 2 hours in an environment at pH 1.
5. The controlled release oral pharmaceutical composition of claim 1 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution for 1 hour in an environment at pH 6.4.
6. The controlled release oral pharmaceutical composition of claim 1 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution for 2 hours in an environment at pH 1 and is resistant to dissolution for 1 hour in an environment at pH 6.4.
7. The controlled release oral pharmaceutical composition of claim 1 , wherein said gastro-resistant substance comprises at least one methacrylic acid polymer.
8. The controlled release oral pharmaceutical composition of claim 1 , wherein said rifamycin SV comprises from about 20% to about 60% by weight of the total weight of said controlled release oral pharmaceutical composition.
9. The controlled release oral pharmaceutical composition of claim 1 , wherein said infection of the colon is caused by gram negative bacteria, gram positive bacteria, or a combination of gram negative bacteria and gram positive bacteria.
10. The controlled release oral pharmaceutical composition of claim 1 , wherein said infection of the colon is infectious colitis, bacillary dysentery, colitis, or diverticulitis.
11. The controlled release oral pharmaceutical composition of claim 1 , wherein said infection of the colon causes diarrhea.
12. The controlled release oral pharmaceutical composition of claim 1 , wherein said infection of the colon causes hyperammonaemia.
13. The controlled release oral pharmaceutical composition of claim 1 , wherein said hydrophilic substance comprises at least one of a hydroxyalkylcellulose, an alkylcellulose, a carboxyalkylcellulose, a polyvinyl alcohol, a carboxyvinyl polymer, a carboxyvinyl copolymer, a polysaccharide, hyduronic acid, glucoronic acid, a glucosamine, or a pectin.
14. The controlled release oral pharmaceutical composition of claim 1 , wherein said amphiphilic substance comprises at least one of a phospholipid, a ceramide, a sphingomyelin, lecithin, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenealkyl, or sorbitan.
15. The controlled release oral pharmaceutical. composition of claim 14 , wherein said amphiphilic substance is lecithin.
16. The controlled release oral pharmaceutical composition of claim 1 , wherein said lipophilic substance comprises at least one of beeswax, carnuba wax, stearic acid, or stearin.
17. A controlled release oral pharmaceutical composition according to claim 1 , wherein said lipophilic substance comprises from about 1% to about 3.4% by weight of the total weight of the controlled release oral pharmaceutical composition.
18. The controlled release oral pharmaceutical composition of claim 1 , wherein said hydrophilic substance comprises from about 8.4% to about 23% by weight of the total weight of the controlled release oral pharmaceutical composition.
19. The controlled release oral pharmaceutical composition of claim 1 , wherein said rifamycin SV is in the form of a sodium salt.
20. The controlled release oral pharmaceutical composition of claim 19 , wherein said sodium salt of rifamycin SV comprises from about 20% to about 60% by weight of the total weight of said controlled release oral pharmaceutical composition.
21. The controlled release oral pharmaceutical composition of claim 13 , wherein said amphiphilic substance comprises at least one of a phospholipid, a ceramide, a sphingomyelin, lecithin, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenealkyl, or sorbitan.
22. The controlled release oral pharmaceutical composition of claim 21 , wherein said amphiphilic substance is lecithin.
23. The controlled release oral pharmaceutical composition of claim 13 , wherein said lipophilic substance comprises at least one of beeswax, carnuba wax, stearic acid, or stearin.
24. The controlled release oral pharmaceutical composition of claim 21 , wherein said lipophilic substance comprises at least one of beeswax, carnuba wax, stearic acid, or stearin.
25. The controlled release oral pharmaceutical composition of claim 22 , wherein said lipophilic substance comprises at least one of beeswax, carnuba wax, stearic acid, or stearin.
26. The controlled release oral pharmaceutical composition of claim 24 , wherein said gastro-resistant substance comprises at least one methacrylic acid polymer.
27. The controlled release oral pharmaceutical composition of claim 25 , wherein said gastro-resistant substance comprises at least one methacrylic acid polymer.