ORAL ANTIMICROBIAL PHARMACEUTICAL COMPOSITIONS
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 tablet comprising granules and at least one hydrophilic compound, wherein the granules comprise:
(a) rifamycin SV;
(b) at least one amphiphilic compound; and
(c) at least one lipophilic compound.
2 . The tablet according to claim 1 , wherein the at least one hydrophilic compound is selected from the group consisting of a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, a polyvinyl alcohol, a carboxyvinyl polymer, a carboxyvinyl copolymer, a polysaccharide derivative, a hyaluronic acid, a glucuronic acid, a glucosamine and a pectin.
3 . The tablet according to claim 1 , wherein the at least one hydrophilic compound is a hydroxyalkyl cellulose or a carboxyalkyl cellulose.
4 . The tablet according to claim 1 , wherein the at least one hydrophilic compound is a hydrophilic copolymeric substance.
5 . The tablet according to claim 1 , wherein the at least one hydrophilic compound is a hydrogel.
6 . The tablet according to claim 1 , wherein the at least one amphiphilic compound is selected from the group consisting of lecithin, a sphingomyelin, a phospholipid, a ceramide, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenated alkyl and a sorbitan derivative.
7 . The tablet according to claim 1 , wherein the at least one amphiphilic compound is lecithin.
8 . The tablet according to claim 1 , wherein the at least one lipophilic compound is selected from the group consisting a wax, stearic acid and stearin.
9 . The tablet according to claim 1 , wherein the at least one lipophilic compound is stearic acid.
10 . The tablet according to claim 1 , further comprising a gastro-resistant film coating.
11 . The tablet according to claim 10 , wherein the gastro-resistant film coating comprises acrylic and/or methacrylic acid polymers, or copolymers, or cellulose phthalate derivatives.
12 . The tablet according to claim 10 , wherein the gastro-resistant film coating comprises acrylic and methacrylic acid copolymers.
13 . A tablet coated with a gastro-resistant film, wherein the gastro-resistant film comprises methacrylic acid polymers and/or copolymers, and the tablet comprises:
(i) a hydrophilic copolymeric substance; and
(ii) granules in the hydrophilic copolymeric substance, wherein the granules comprise:
(a) rifamycin SV;
(b) lecithin; and
(c) stearic acid.
14 . A tablet comprising rifamycin SV, at least one amphiphilic compound, at least one lipophilic compound and at least one hydrophilic compound prepared by a process comprising the steps:
(a) mixing rifamycin SV, at least one amphiphilic compound and at least one lipophilic compound to form a first mixture;
(b) granulating the first mixture to form granules;
(c) mixing the granules with at least one hydrophilic compound to form a second mixture; and
(d) tableting the second mixture to form a tablet.
15 . The tablet according to claim 14 , wherein the at least one hydrophilic compound is selected from the group consisting of a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, a polyvinyl alcohol, a carboxyvinyl polymer, a carboxyvinyl copolymer, a polysaccharide derivative, a hyaluronic acid, a glucuronic acid, a glucosamine and a pectin.
16 . The tablet according to claim 14 , wherein the at least one hydrophilic compound is a hydroxyalkyl cellulose or a carboxyalkyl cellulose.
17 . The tablet according to claim 14 wherein the at least one hydrophilic compound is a hydrophilic copolymeric substance.
18 . The tablet according to claim 14 , wherein the at least one hydrophilic compound is a hydrogel.
19 . The tablet according to claim 14 , wherein the at least one amphiphilic compound is selected from the group consisting of lecithin, a sphingomyelin, a phospholipid, a ceramide, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenated alkyl and a sorbitan derivative.
20 . The tablet according to claim 14 , wherein the at least one amphiphilic compound is lecithin.
21 . The tablet according to claim 14 , wherein the at least one lipophilic compound is selected from the group consisting a wax, stearic acid and stearin.
22 . The tablet according to claim 14 , wherein the at least one lipophilic compound is stearic acid.
23 . The tablet according to claim 14 , wherein the tablet further comprises a gastro-resistant film coating prepared by (e) coating the tablet of step (d).
24 . The tablet according to claim 23 , wherein the gastro-resistant film coating comprises acrylic and/or methacrylic acid polymers, or copolymers, or cellulose phthalate derivatives.
25 . The tablet according to claim 23 , wherein the gastro-resistant film coating comprises acrylic and methacrylic acid copolymers.
26 . A tablet comprising rifamycin SV, at least one amphiphilic compound, at least one lipophilic compound and at least one hydrophilic compound prepared by a process comprising the steps:
(a) mixing rifamycin SV and at least one amphiphilic compound to form a first mixture;
(b) mixing the first mixture with the at least one lipophilic compound to form a second mixture;
(c) mixing the second mixture with the at least one hydrophilic compound to form a third mixture; and
(d) tableting the third mixture to form a tablet.
27 . The tablet according to claim 26 , wherein the at least one hydrophilic compound is selected from the group consisting of a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, a polyvinyl alcohol, a carboxyvinyl polymer, a carboxyvinyl copolymer, a polysaccharide derivative, a hyaluronic acid, a glucuronic acid, a glucosamine and a pectin.
28 . The tablet according to claim 26 , wherein the at least one hydrophilic compound is a hydroxyalkyl cellulose or a carboxyalkyl cellulose.
29 . The tablet according to claim 26 wherein the at least one hydrophilic compound is a hydrophilic copolymeric substance.
30 . The tablet according to claim 26 , wherein the at least one hydrophilic compound is a hydrogel.
31 . The tablet according to claim 26 , wherein the at least one amphiphilic compound is selected from the group consisting of lecithin, a sphingomyelin, a phospholipid, a ceramide, an alkyl block copolymer, a salt of a sulphated alkyl acid, a polyoxyethylenated alkyl and a sorbitan derivative.
32 . The tablet according to claim 26 , wherein the at least one amphiphilic compound is lecithin.
33 . The tablet according to claim 26 , wherein the at least one lipophilic compound is selected from the group consisting a wax, stearic acid and stearin.
34 . The tablet according to claim 26 , wherein the at least one lipophilic compound is stearic acid.
35 . The tablet according to claim 26 , wherein the tablet further comprises a gastro-resistant film coating prepared by (e) coating the tablet of step (d).
36 . The tablet according to claim 35 , wherein the gastro-resistant film coating comprises acrylic and/or methacrylic acid polymers, or copolymers, or cellulose phthalate derivatives.
37 . The tablet according to claim 35 , wherein the gastro-resistant film coating comprises acrylic and methacrylic acid copolymers.
38 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 1 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis.
39 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 1 , wherein the pathological condition is travellers' diarrhoea.
40 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 1 , wherein the pathological condition is diverticular disease and/or diverticulitis.
41 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 13 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis.
42 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 13 , wherein the pathological condition is travellers' diarrhoea.
43 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 13 , wherein the pathological condition is diverticular disease and/or diverticulitis.
44 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 14 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis.
45 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 14 , wherein the pathological condition is travellers' diarrhoea.
46 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 14 , wherein the pathological condition is diverticular disease and/or diverticulitis.
47 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 26 , wherein the pathological condition is infectious colitis, bacillary dysentery, pseudomembranous colitis, travellers' diarrhoea, diverticular disease and/or diverticulitis.
48 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 26 , wherein the pathological condition is travellers' diarrhoea.
49 . A method of treating a pathological condition of the colon comprising administering to a patient in need thereof the controlled release oral pharmaceutical composition according to claim 26 , wherein the pathological condition is diverticular disease and/or diverticulitis.