Compositions for veterinary and medical applications
Compositions including polymeric dialdehydes and compounds of where R 1 , R 2 , R 7 , R 8 , R 9 , and R 10 may be the same or different and are selected from H, CH 3 , OH, OCH 3 , C 2 H 5 , OC 2 H 5 OCH 2 Ph, OCH 2 PhNO 2 , F or Cl; R 3 , R 4 , R 5 , R 6 may be the same or different and are selected from H, CH 3 , OCH 3 , C 2 H 5 , OC 2 H 5 OCH 2 Ph, OCH 2 PhNO 2 , F or Cl, or R 5 and R 6 are the same or different and are selected from H, CH 3 , OCH 3 , C 2 H 5 , OC 2 H 5 OCH 2 Ph, OCH 2 PhNO 2 , F or Cl and R 3 and R 4 together are ═O, or R 4 and R 6 are the same or different and are selected from H, CH 3 , OCH 3 , C 2 H 5 , OC 2 H 5 OCH 2 Ph, OCH 2 PhNO 2 , F or Cl and R 3 and R 5 together form a double bond or are ═O, or R 3 and R 4 , are the same or different and are selected from H, CH 3 , OCH 3 , C 2 H 5 , OC 2 H 5 OCH 2 Ph, OCH 2 PhNO 2 , F or Cl and R 5 and R 6 together are ═O; R 11 and R 12 together form ═CH 2 , or R 11 and R 12 may be the same or different and are independently selected from the group consisting of H, CH 3 , CH 2 CH 3 and CH 2 CH 2 CH 3 ; and X is selected from the group consisting of Cl, Br, SO 4 , I and R 13 COO, where R 13 is CH 3 or poly acids, for the treatment of gastrointestinal functional disorders or related conditions as well as for the promotion of general health and weight gain in animals including humans.
1. A composition comprising a synergistically effective amount of a compound of Formula (1) and a dialdehyde polysaccharide for the treatment of gastrointestinal (GI) functional disorders or related conditions or for promoting weight gain in animals, where Formula (1) consists of:
where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are hydrogen and R 11 and R 12 together form ═CH 2 ; and
X is selected from the group consisting of Cl, Br, SO 4 , I and R 13 COO, where R 13 is CH 3 or poly acids.
2. A composition according to claim 1 wherein the GI functional disorders or related conditions are selected from the group consisting of Irritable Bowel Syndrome (IBS); Inflammatory Bowel Disease (IBD), Colitis, Crohn's disease and coeliac disease.
3. A composition according to claim 1 wherein the animals are selected from the group consisting of humans and other primates, birds, ungulates, sheep, cervidae and swine, fish, crustaceans, molluscs, reptiles, rodents, canines and felines.
4. A composition according to claim 1 for promoting weight gain in humans, birds, ungulates, fish, reptiles, rodents, canines or felines.
5. A composition according to claim 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are hydrogen, R 11 and R 12 together form ═CH 2 and X − is Cl so that the compound of Formula (1) is berberine chloride.
6. A composition comprising a synergistically effective amount of a compound of Formula (1) and a polymeric dialdehyde wherein the polymeric dialdehyde is a dialdehyde polysaccharide of Formula (2), wherein Formula (1) consists of:
where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are hydrogen and R 11 and R 12 together form ═CH 2 ; and
X is selected from the group consisting of Cl, Br, SO 4 , I and R 13 COO, where R 13 is CH 3 or poly acids;
and where Formula (2) consists of:
wherein each of the monomers R p and R r , are independently selected from the group consisting of:
and each monomer R q is independently selected from the group consisting of:
wherein each R 14 may be the same or different and is independently selected from the group consisting of CH 2 OH, COOH, CH 2 OCH 2 COOH and CH 2 OR 15 , where R 15 is selected from the group consisting of CH 2 C 6 H 4 COOH, C 6 H 4 COOH and CH 2 (CH 2 ) y COOH where y=1 to 20;
wherein p 1 . . . p n may be the same or different and are each independently selected from the range 0 to n; q 1 . . . q n may be the same or different and are each independently selected from the range 1 to m; r 1 . . . r n may be the same or different and are each independently selected from the range of 0 to n, n is an integer greater than 0 and m is an integer greater than 1; and wherein
q
1
+
⋯
+
q
n
p
1
+
⋯
+
p
n
+
q
1
+
⋯
+
q
n
+
r
1
+
⋯
+
r
n
⨯
100
%
≥
30
%
.
7. A composition according to claim 6 wherein each R p and R r are (A) and R q is (D), so that the dialdehyde polysaccharide is oxidised cellulose.
8. A composition according to claim 7 wherein Formula (1) is berberine chloride and wherein the oxidised cellulose is 30 to 100% oxidised monomer.
9. A composition according to claim 8 wherein the oxidised cellulose comprises from 40 to 60% oxidised monomer.
10. A composition according to claim 7 wherein R 14 is CH 2 OH or CH 2 OCH 2 COOH.
11. A composition according to claim 6 wherein each R p and R r are (B) and R q is (E), so that the dialdehyde polysaccharide is oxidised starch or dextrin.
12. A composition according to claim 6 wherein each R p and R r are (C) and R q is (F) and/or (G) so that the dialdehyde polysaccharide is oxidised dextran.
13. A composition according to claim 6 , wherein:
q
1
+
⋯
+
q
n
p
1
+
⋯
+
p
n
+
q
1
+
⋯
+
q
n
+
r
1
+
⋯
+
r
n
⨯
100
%
≥
40
%
.
14. A composition according to claim 6 , wherein:
40
%
≤
q
1
+
⋯
+
q
n
p
1
+
⋯
+
p
n
+
q
1
+
⋯
+
q
n
+
r
1
+
⋯
+
r
n
⨯
100
%
≤
60
%
.
15. A composition according to claim 6 wherein the compound of Formula (2) has a molecular weight of from 1,000 to 1,000,000 Daltons.
16. A composition according to claim 15 wherein the compound of Formula (2) has a molecular weight of from 10,000 to 750,000 Daltons.
17. A composition according to claim 6 wherein the compound of Formula (2) is water-insoluble and has a particle size of from 5μ to 100μ.
18. A composition according to claim 17 wherein the compound of Formula (2) has a particle size of from 5μ to 30μ.
19. A composition according to claim 6 , where the weight ratio of Formula (1) to Formula (2) ranges from 1:1 to 1:100.
20. A composition according to claim 19 wherein the weight ratio of Formula (1) to Formula (2) ranges from 1:10 to 1:40.
21. A composition including a compound of Formula (1) and a dialdehyde polysaccharide for the treatment of gastrointestinal (GI) functional disorders or related conditions or for promoting weight gain in animals, where Formula (1) is:
where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are hydrogen and R 11 and R 12 together form ═CH 2 ; and
X is selected from the group consisting of Cl, Br, SO 4 , I and R13COO, where R 13 is CH3 or poly acids
and wherein the compound of Formula (1) is present at a concentration that provides a dosage of less than about 6 mg/kg/day and the dialdehyde polysaccharide is present at a concentration that provides a dosage of less than about 250 mg/kg/day.
22. The composition of claim 21 wherein the compound of Formula (1) is present at a concentration that provides a dosage of less between about 0.5 mg-6 mg/kg/day and the dialdehyde polysaccharide is present at a concentration that provides a dosage of about 5 mg-200 mg/kg/day.
23. A composition including a compound of Formula (1) and a dialdehyde polysaccharide for the treatment of gastrointestinal (GI) functional disorders or related conditions or for promoting weight gain in animals, where Formula (1) is:
where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are hydrogen and R 11 and R 12 together form ═CH 2 ; and
X is selected from the group consisting of Cl, Br, SO4, I and R13COO, where R13 is CH3 or poly acids
and wherein the compound of Formula (1) is present at a concentration that provides a dosage of less than about 6 mg/kg/day and the dialdehyde polysaccharide is present at a concentration that provides a dosage of less than about 250 mg/kg/day, wherein the dialdehyde polysaccharide is 40% oxidized cellulose.