U.S. patent application number 12/945605 was filed with the patent office on 2011-03-10 for compositions and methods for the treatment of gastrointestinal indications.
This patent application is currently assigned to COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH. Invention is credited to Suresh Babu KATRAGADDA, Manjulatha KHANAPUR, Venkata Srinivas PULLELA, Muralidhar Gurachar PUROHIT, Janaswamy Madusudana RAO, Hari Babu TATIPAKA, Jhillu Singh YADAV.
Application Number | 20110059913 12/945605 |
Document ID | / |
Family ID | 38235442 |
Filed Date | 2011-03-10 |
United States Patent
Application |
20110059913 |
Kind Code |
A1 |
RAO; Janaswamy Madusudana ;
et al. |
March 10, 2011 |
COMPOSITIONS AND METHODS FOR THE TREATMENT OF GASTROINTESTINAL
INDICATIONS
Abstract
The present invention relates to identification of Oroxylum
indicum, Indian medicinal plant as a rich source for flavanoid
compounds. Mucoprotective and antigastric ulcer properties in the
flavone class of compounds isolated therefrom have been identified
along with a flavanoids mixture in substantial yields from hexane
and acetone extracts. The hexane extract was fractionated, purified
and the compounds identified as Oroxylin A, Chrysin and Baicalein.
The acetone extract was purified and the compounds obtained
identified as methoxy chrysin, Oroxyloside methyl ester and
chrysin-7-O-methyl glycoside.
Inventors: |
RAO; Janaswamy Madusudana;
(Andhra Pradesh, IN) ; KATRAGADDA; Suresh Babu;
(Andhra Pradesh, IN) ; TATIPAKA; Hari Babu;
(Andhra Pradesh, IN) ; KHANAPUR; Manjulatha;
(Andhra Pradesh, IN) ; PUROHIT; Muralidhar Gurachar;
(Andhra Pradesh, IN) ; PULLELA; Venkata Srinivas;
(Andhra Pradesh, IN) ; YADAV; Jhillu Singh;
(Andhra Pradesh, IN) |
Assignee: |
COUNCIL OF SCIENTIFIC AND
INDUSTRIAL RESEARCH
New Delhi
IN
|
Family ID: |
38235442 |
Appl. No.: |
12/945605 |
Filed: |
November 12, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11651106 |
Jan 9, 2007 |
7855200 |
|
|
12945605 |
|
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Current U.S.
Class: |
514/27 ;
514/233.5; 514/254.11; 514/320; 514/456 |
Current CPC
Class: |
A61K 31/7048 20130101;
A61P 1/04 20180101; A61K 31/353 20130101 |
Class at
Publication: |
514/27 ;
514/254.11; 514/456; 514/233.5; 514/320 |
International
Class: |
A61K 31/7048 20060101
A61K031/7048; A61K 31/496 20060101 A61K031/496; A61K 31/353
20060101 A61K031/353; A61K 31/5377 20060101 A61K031/5377; A61K
31/453 20060101 A61K031/453; A61P 1/04 20060101 A61P001/04 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 9, 2006 |
IN |
74/DEL/2006 |
Claims
1. Method for treatment of gastric ulcer comprising administering
to a subject a pharmaceutically acceptable amount of a
mucoprotective and antigastric ulcer agent selected the group
consisting of OA-5 and analogues thereof, selected in turn from the
group consisting of NMC-2, NMC-3, CHN-2, CHM-3, CPP-2, CG, and
CGL.
2.-6. (canceled)
7. The method of claim 1 wherein, OA-5 provides reduced glandular
ulcer index up to 78.22% induced by cold stress restraint
ulceration at dose level of 50 mg/kg of bodyweight in comparison
with the reference standard ranitidine up to 78.83% reduction of
ulcer index at dose level of 50 mg/kg of bodyweight.
8. The method of claim 1 wherein, OA-5 provides reduced glandular
ulcer index up to 75.45% induced by cold stress restraint
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with the reference standard ranitidine up to 78.83% reduction of
ulcer index at dose level of 50 mg/kg of bodyweight.
9. The method of claim 1 wherein, OA-5 provides reduced glandular
ulcer index up to 50.14% induced by cold stress restraint
ulceration at dose level of 15 mg/kg of bodyweight in comparison
with the reference standard ranitidine up to 78.83% reduction of
ulcer index at dose level of 50 mg/kg of bodyweight.
10. The method of claim 1 wherein, OA-5 provides reduced glandular
ulcer index up to 41.92% induced by cold stress restraint
ulceration at dose level of 10 mg/kg of bodyweight in comparison
with the reference standard ranitidine up to 78.83% reduction of
ulcer index at dose level of 50 mg/kg of bodyweight.
11. The method of claim 1 wherein, OA-5 provides reduced glandular
ulcer index up to 31.55% induced by cold stress restraint
ulceration at dose level of 5 mg/kg of bodyweight in comparison
with the reference standard ranitidine up to 78.83% reduction of
ulcer index at dose level of 50 mg/kg of bodyweight.
12. The method of claim 1 wherein, OA-5 provides marked gastric
mucosal protection up to 85.00% induced by 50% ethanol ulceration
at dose level of 50 mg/kg of bodyweight in comparison with
reference to the standard ranitidine up to 61.26% gastric mucosal
protection at dose level of 50 mg/kg of bodyweight in comparison
with the reference to standard omeprazole up to 67.51% gastric
mucosal protection at dose level of 30 mg/kg of bodyweight and in
comparison with the reference to standard sucralfate up to 87.5%
gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
13. The method of claim 1 wherein, OA-5 provides marked gastric
mucosal protection up to 82.5% induced by 50% ethanol ulceration at
dose level of 25 mg/kg of bodyweight in comparison with reference
to the standard ranitidine up to 61.26% gastric mucosal protection
at dose level of 50 mg/kg of bodyweight in comparison with the
reference to standard omeprazole up to 67.51% gastric mucosal
protection at dose level of 30 mg/kg of bodyweight and in
comparison with the reference to standard sucralfate up to 87.5%
gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
14. The method of claim 1 wherein, 0A-5 provides marked gastric
mucosal protection up to 60.61% induced by 50% ethanol ulceration
at dose level of 15 mg/kg of bodyweight in comparison with
reference to the standard ranitidine up to 61.26% gastric mucosal
protection at dose level of 50 mg/kg of bodyweight in comparison
with the reference to standard omeprazole up to 67.51% gastric
mucosal protection at dose level of 30 mg/kg of bodyweight and in
comparison with the reference to standard sucralfate up to 87.5%
gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
15. The method of claim 1 wherein, OA-5 provides marked gastric
mucosal protection up to 35.00% induced by 50% ethanol ulceration
at dose level of 10 mg/kg of bodyweight in comparison with
reference to the standard ranitidine up to 61.26% gastric mucosal
protection at dose level of 50 mg/kg of bodyweight in comparison
with the reference to standard omeprazole up to 67.51% gastric
mucosal protection at dose level of 30 mg/kg of bodyweight and in
comparison with the reference to standard sucralfate up to 87.5%
gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
16. The method of claim 1 wherein, OA-5 provides marked gastric
mucosal protection up to 30.01% induced by 50% ethanol ulceration
at dose level of 5 mg/kg of bodyweight in comparison with reference
to the standard ranitidine up to 61.26% gastric mucosal protection
at dose level of 50 mg/kg of bodyweight in comparison with the
reference to standard omeprazole up to 67.51% gastric mucosal
protection at dose level of 30 mg/kg of bodyweight and in
comparison with the reference to standard sucralfate up to 87.5%
gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
17. The method of claim 1 wherein, OA-5 provides elevation pH up to
4.95 induced by 50% ethanol ulceration at dose level of 50 mg/kg of
bodyweight comparison with reference standard ranitidine up to 4.96
pH elevation at dose level of 50 mg/kg of bodyweight in comparison
with the reference standard omeprazole up to 4.65 pH elevation at
dose level of 30 mg/kg of bodyweight and comparison with the
reference standard sucralfate up to 4.00 pH elevation at dose level
of 400 mg/kg of bodyweight.
18. The method of claim 1 wherein, OA-5 provides elevation pH up to
6.81 induced by 50% ethanol ulceration at dose level of 25 mg/kg of
bodyweight in comparison with reference standard ranitidine up to
4.96 pH elevation at dose level of 50 mg/kg of bodyweight in
comparison with the reference standard omeprazole up to 4.65 pH
elevation at dose level of 30 mg/kg of bodyweight and comparison
with the reference standard sucralfate up to 4.00 pH elevation at
dose level of 400 mg/kg of bodyweight.
19. The method of claim 1 wherein, OA-5 provides elevation pH up to
4.5 induced by 50% ethanol ulceration at dose level of 15 mg/kg of
bodyweight in comparison with reference standard ranitidine up to
4.96 pH elevation at dose level of 50 mg/kg of bodyweight in
comparison with the reference standard omeprazole up to 4.65 pH
elevation at dose level of 30 mg/kg of bodyweight and comparison
with the reference standard sucralfate up to 4.00 pH elevation at
dose level of 400 mg/kg of bodyweight.
20. The method of claim 1 wherein, OA-5 provides elevation pH up to
4.66 induced by 50% ethanol ulceration at dose level of 10 mg/kg of
bodyweight in comparison with reference standard ranitidine up to
4.96 pH elevation at dose level of 50 mg/kg of bodyweight in
comparison with the reference standard omeprazole up to 4.65 pH
elevation at dose level of 30 mg/kg of bodyweight and comparison
with the reference standard sucralfate up to 4.00 pH elevation at
dose level of 400 mg/kg of bodyweight.
21. The method of claim 1 wherein, OA-5 provides elevation pH up to
3.5 induced by 50% ethanol ulceration at dose level of 5 mg/kg of
bodyweight in comparison with reference standard ranitidine up to
4.96 pH elevation at dose level of 50 mg/kg of bodyweight in
comparison with the reference standard omeprazole up to 4.65 pH
elevation at dose level of 30 mg/kg of bodyweight and comparison
with the reference standard sucralfate up to 4.00 pH elevation at
dose level of 400 mg/kg of bodyweight.
22. The method of claim 1 wherein, OA-5 provides increase gastric
juice secretion up to 7.4 ml induced by 50% ethanol ulceration at
dose level of 50 mg/kg of bodyweight comparison with reference
standard ranitidine up to 5.0 ml gastric juice secretion at dose
level of 50 mg/kg of bodyweight in comparison with the reference
standard omeprazole up to 3.5 ml gastric juice secretion at dose
level of 30 mg/kg of bodyweight and comparison with the reference
standard sucralfate up to 4.00 ml gastric juice secretion at dose
level of 400 mg/kg of bodyweight.
23. The method of claim 1 wherein, OA-5 provides increase gastric
juice secretion up to 5.5 ml induced by 50% ethanol ulceration at
dose level of 25 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 5.0 ml gastric juice secretion at dose
level of 50 mg/kg of bodyweight in comparison with the reference
standard omeprazole up to 3.5 ml gastric juice secretion at dose
level of 30 mg/kg of bodyweight and comparison with the reference
standard sucralfate up to 4.00 ml gastric juice secretion at dose
level of 400 mg/kg of bodyweight.
24. The method of claim 1 wherein, OA-5 provides increase gastric
juice secretion up to 4.5 ml induced by 50% ethanol ulceration at
dose level of 15 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 5.0 ml gastric juice secretion at dose
level of 50 mg/kg of bodyweight in comparison with the reference
standard omeprazole up to 3.5 ml gastric juice secretion at dose
level of 30 mg/kg of bodyweight and comparison with the reference
standard sucralfate up to 4.00 ml gastric juice secretion at dose
level of 400 mg/kg of bodyweight.
25. The method of claim 1 wherein, OA-5 provides increase gastric
juice secretion up to 4.2 ml induced by 50% ethanol ulceration at
dose level of 10 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 5.0 ml gastric juice secretion at dose
level of 50 mg/kg of bodyweight in comparison with the reference
standard omeprazole up to 3.5 ml gastric juice secretion at dose
level of 30 mg/kg of bodyweight and comparison with the reference
standard sucralfate up to 4.00 ml gastric juice secretion at dose
level of 400 mg/kg of bodyweight.
26. The method of claim 1 wherein, OA-5 provides increase gastric
juice secretion up to 4.0 ml induced by 50% ethanol ulceration at
dose level of 5 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 5.0 ml gastric juice secretion at dose
level of 50 mg/kg of bodyweight in comparison with the reference
standard omeprazole up to 3.5 ml gastric juice secretion at dose
level of 30 mg/kg of bodyweight and comparison with the reference
standard sucralfate up to 4.00 ml gastric juice secretion at dose
level of 400 mg/kg of bodyweight.
27. The method of claim 1 wherein, OA-5 provides reduction in
acidity level up to 18.25 m Eg induced by 50% ethanol ulceration at
dose level of 50 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 26.74 m Eg mean level of reduction in
acidity at dose level of 50 mg/kg of bodyweight, in comparison with
the reference standard omeprazole up to 32.01 m Eg mean level of
reduction in acidity at dose level of 30 mg/kg of bodyweight and in
comparison with the reference standard sucralfate up to 52.00 m Eg
mean level of reduction in acidity at dose level of 400 mg/kg of
bodyweight.
28. The method of claim 1 wherein, OA-5 provides reduction in
acidity level up to 12.4 m Eg induced by 50% ethanol ulceration at
dose level of 25 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 26.74 m Eg mean level of reduction in
acidity at dose level of 50 mg/kg of bodyweight, in comparison with
the reference standard omeprazole up to 32.01 m Eg mean level of
reduction in acidity at dose level of 30 mg/kg of bodyweight and in
comparison with the reference standard sucralfate up to 52.00 m Eg
mean level of reduction in acidity at dose level of 400 mg/kg of
bodyweight.
29. The method of claim 1 wherein, OA-5 provides reduction in
acidity level up to 29.66 m Eg induced by 50% ethanol ulceration at
dose level of 15 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 26.74 m Eg mean level of reduction in
acidity at dose level of 50 mg/kg of bodyweight, in comparison with
the reference standard omeprazole up to 32.01 m Eg mean level of
reduction in acidity at dose level of 30 mg/kg of bodyweight and in
comparison with the reference standard sucralfate up to 52.00 m Eg
mean level of reduction in acidity at dose level of 400 mg/kg of
bodyweight.
30. The method as claimed in claim 1 wherein, OA-5 provides
reduction in acidity level up to 31.33 m Eg induced by 50% ethanol
ulceration at dose level of 10 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 26.74 m Eg mean level of
reduction in acidity at dose level of 50 mg/kg of bodyweight, in
comparison with the reference standard omeprazole up to 32.01 m Eg
mean level of reduction in acidity at dose level of 30 mg/kg of
bodyweight and in comparison with the reference standard sucralfate
up to 52.00 m Eg mean level of reduction in acidity at dose level
of 400 mg/kg of bodyweight.
31. The method as claimed in claim 1 wherein, OA-5 provides
reduction in acidity level up to 42.66 m Eg induced by 50% ethanol
ulceration at dose level of 5 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 26.74 m Eg mean level of
reduction in acidity at dose level of 50 mg/kg of bodyweight, in
comparison with the reference standard omeprazole up to 32.01 m Eg
mean level of reduction in acidity at dose level of 30 mg/kg of
bodyweight and in comparison with the reference standard sucralfate
up to 52.00 m Eg mean level of reduction in acidity at dose level
of 400 mg/kg of bodyweight.
32. The method as claimed in claim 1 wherein, OA-5 provides marked
gastric mucosal protection up to 79.85% induced by pylorus ligated
ulceration at dose level of 50 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
33. The method as claimed in claim 1 wherein, OA-5 provides marked
gastric mucosal protection up to 75.07% induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
34. The method as claimed in claim 1 wherein, OA-5 provides marked
gastric mucosal protection up to 70.07% induced by pylorus ligated
ulceration at dose level of 15 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
35. The method as claimed in claim 1 wherein, OA-5 provides marked
gastric mucosal protection up to 59.78% induced by pylorus ligated
ulceration at dose level of 10mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
36. The method as claimed in claim 1 wherein, OA-5 provides marked
gastric mucosal protection up to 46.80% induced by pylorus ligated
ulceration at dose level of 5 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
37. The method as claimed in claim 1 wherein, OA-5 provides
elevation pH up to 4.62 induced by pylorus ligated ulceration at
dose level of 50 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
38. The method as claimed in claim 1 wherein, OA-5 provides
elevation pH up to 5.62 induced by pylorus ligated ulceration at
dose level of 25 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
39. The method as claimed in claim 1 wherein, 0A-5 provides
elevation pH up to 4.35 induced by pylorus ligated ulceration at
dose level of 15 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
40. The method as claimed in claim 1 wherein, OA-5 provides
elevation pH up to 3.58 induced by pylorus ligated ulceration at
dose level of 10 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
41. The method as claimed in claim 1 wherein, OA-5 provides
elevation pH up to 3.25 induced by pylorus ligated ulceration at
dose level of 5 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
42. The method as claimed in claim 1 wherein, OA-5 provides
increase in gastric juice secretion up to 2.5 ml induced by pylorus
ligated ulceration at dose level of 50 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 1.82 ml gastric
juice secretion at dose level of 50 mg/kg of bodyweight.
43. The method as claimed in claim 1 wherein, OA-5 provides
increase in gastric juice secretion up to 2.1 ml induced by pylorus
ligated ulceration at dose level of 50 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 1.82 ml gastric
juice secretion at dose level of 50 mg/kg of bodyweight.
44. The method as claimed in claim 1 wherein, OA-5 provides
increase in gastric juice secretion up to 3.62 ml induced by
pylorus ligated ulceration at dose level of 15 mg/kg of bodyweight
in comparison with reference standard ranitidine up to 1.82 ml
gastric juice secretion at dose level of 50 mg/kg of
bodyweight.
45. The method as claimed in claim 1 wherein, OA-5 provides
increase in gastric juice secretion up to 3.5 ml induced by pylorus
ligated ulceration at dose level of 5 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 1.82 ml gastric
juice secretion at dose level of 50 mg/kg of bodyweight.
46. The method as claimed in claim 1 wherein, OA-5 provides
reduction in acidity level up to 32.66 m Eg induced by pylorus
ligated ulceration at dose level of 50 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 31.8 m Eg mean
level of reduction in acidity at dose level of 50 mg/kg of
bodyweight.
47. The method as claimed in claim 1 wherein, OA-5 provides
reduction in acidity level up to 30.18 m Eg induced by pylorus
ligated ulceration at dose level of 25 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 31.8 m Eg mean
level of reduction in acidity at dose level of 50 mg/kg of
bodyweight.
48. The method as claimed in claim 1 wherein, OA-5 provides
reduction in acidity level up to 30.25 m Eg induced by pylorus
ligated ulceration at dose level of 15 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 31.8 m Eg mean
level of reduction in acidity at dose level of 50 mg/kg of
bodyweight.
49. The method as claimed in claim 1 wherein, OA-5 provides
reduction in acidity level up to 42.9 m Eg induced by pylorus
ligated ulceration at dose level of 10 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 31.8 m Eg mean
level of reduction in acidity at dose level of 50 mg/kg of
bodyweight.
50. The method as claimed in claim 1 wherein, OA-5 provides
reduction in acidity level up to 45.5 m Eg induced by pylorus
ligated ulceration at dose level of 5 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 31.8 m Eg mean
level of reduction in acidity at dose level of 50 mg/kg of
bodyweight.
51. The method as claimed in claim 1 wherein, NMC-2 provides
reduced glandular ulcer index up to 59.67% induced by cold stress
restraint ulceration at dose level of 25 mg/kg of bodyweight in
comparison with the reference standard ranitidine up to 78.83%
reduction of ulcer index at dose level of 50 mg/kg of
bodyweight.
52. The method as claimed in claim 1 wherein, NMC-2 provides
gastric mucosal protection up to 57.5% induced by 50% ethanol
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 61.26% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight in
comparison with the reference to standard omeprazole up to 67.51%
gastric mucosal protection at dose level of 30 mg/kg of bodyweight
and in comparison with the reference to standard sucralfate up to
87.5% gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
53. The method as claimed in claim 1 wherein, NMC-2 provides
elevation pH up to 4.75 induced by 50% ethanol ulceration at dose
level of 25 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.96 pH elevation at dose level of 50
mg/kg of bodyweight in comparison with the reference standard
omeprazole up to 4.65 pH elevation at dose level of 30 mg/kg of
bodyweight and comparison with the reference standard sucralfate up
to 4.00 pH elevation at dose level of 400 mg/kg of bodyweight.
54. The method as claimed in claim 1 wherein, NMC-2 provides
increase gastric juice secretion up to 4.8 ml induced by 50%
ethanol ulceration at dose level of 25 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 5.0 ml gastric
juice secretion at dose level of 50 mg/kg of bodyweight in
comparison with the reference standard omeprazole up to 3.5 ml
gastric juice secretion at dose level of 30 mg/kg of bodyweight and
comparison with the reference standard sucralfate up to 4.00 ml
gastric juice secretion at dose level of 400 mg/kg of
bodyweight.
55. The method as claimed in claim 1 wherein, NMC-2 provides
reduction in acidity level up to 30.8 m Eg induced by 50% ethanol
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 26.74 m Eg mean level of
reduction in acidity at dose level of 50 mg/kg of bodyweight, in
comparison with the reference standard omeprazole up to 32.01 m Eg
mean level of reduction in acidity at dose level of 30 mg/kg of
bodyweight and in comparison with the reference standard sucralfate
up to 52.00 m Eg mean level of reduction in acidity at dose level
of 400 mg/kg of bodyweight.
56.-59. (canceled)
60. The method as claimed in claim 1 wherein, NMC-3 provides
reduced glandular ulcer index up to 57.92% induced by cold stress
restraint ulceration at dose level of 25 mg/kg of bodyweight in
comparison with the reference standard ranitidine up to 78.83%
reduction of ulcer index at dose level of 50 mg/kg of
bodyweight.
61. The method as claimed in claim 1 wherein, CHN-2 provides
reduced glandular ulcer index up to 56.12% induced by cold stress
restraint ulceration at dose level of 25 mg/kg of bodyweight in
comparison with the reference standard ranitidine up to 78.83%
reduction of ulcer index at dose level of 50 mg/kg of
bodyweight.
62. The method as claimed in claim 1 wherein, CHM-3 provides
reduced glandular ulcer index up to 52.64% induced by cold stress
restraint ulceration at dose level of 25 mg/kg of bodyweight in
comparison with the reference standard ranitidine up to 78.83%
reduction of ulcer index at dose level of 50 mg/kg of
bodyweight.
63. The method as claimed in claim 1 wherein, CPP-2 provides
reduced glandular ulcer index up to 61.44% induced by cold stress
restraint ulceration at dose level of 25 mg/kg of bodyweight in
comparison with the reference standard ranitidine up to 78.83%
reduction of ulcer index at dose level of 50 mg/kg of
bodyweight.
64. The method as claimed in claim 1 wherein, CHN-2 provides marked
gastric mucosal protection up to 58.44% induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
65. The method as claimed in claim 1 wherein, CHN-2 provides
elevation pH up to 4.25 induced by pylorus ligated ulceration at
dose level of 25 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
66. The method as claimed in claim 1 wherein, CHN-2 provides
increase in gastric juice secretion up to 1.8 ml induced by pylorus
ligated ulceration at dose level of 25 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 1.82 ml gastric
juice secretion at dose level of 50 mg/kg of bodyweight.
67. The method as claimed in claim 1 wherein, CHN-2 provides
reduction in acidity level up to 31.18 m Eg induced by pylorus
ligated ulceration at dose level of 25 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 31.8 m Eg mean
level of reduction in acidity at dose level of 50 mg/kg of
bodyweight.
68. The method as claimed in claim 1 wherein, CPP-2 provides marked
gastric mucosal protection up to 68.47% induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
69. The method as claimed in claim 1 wherein, CPP-2 provides
elevation pH up to 3.25 induced by pylorus ligated ulceration at
dose level of 25 mg/kg of body weight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
70. The method as claimed in claim 1 wherein, CPP-2 provides
increase in gastric juice secretion up to 2.6 ml induced by pylorus
ligated ulceration at dose level of 25 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 1.82 ml gastric
juice secretion at dose level of 50 mg/kg of bodyweight.
71. The method as claimed in claim 1 wherein, CPP-2 provides
reduction in acidity level up to 29.06 m Eg induced by pylorus
ligated ulceration at dose level of 25 mg/kg of bodyweight in
comparison with reference standard ranitidine up to 31.8 m Eg mean
level of reduction in acidity at dose level of 50 mg/kg of
bodyweight.
72.-73. (canceled)
74. The method as claimed in claim 1 wherein, CGL provides reduced
glandular ulcer index up to 50.22% induced by cold stress restraint
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with the reference standard ranitidine up to 78.83% reduction of
ulcer index at dose level of 50 mg/kg of bodyweight.
75. The method as claimed in claim 1 wherein, CG provides gastric
mucosal protection up to 52.5% induced by 50% ethanol ulceration at
dose level of 25 mg/kg of bodyweight in comparison with reference
to the standard ranitidine up to 61.26% gastric mucosal protection
at dose level of 50 mg/kg of bodyweight in comparison with the
reference to standard omeprazole up to 67.51% gastric mucosal
protection at dose level of 30 mg/kg of bodyweight and in
comparison with the reference to standard sucralfate up to 87.5%
gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
76. The method as claimed in claim 1 wherein, CG provides elevation
pH up to 5.9 induced by 50% ethanol ulceration at dose level of 25
mg/kg of bodyweight in comparison with reference standard
ranitidine up to 4.96 pH elevation at dose level of 50 mg/kg of
bodyweight in comparison with the reference standard omeprazole up
to 4.65 pH elevation at dose level of 30 mg/kg of bodyweight and
comparison with the reference standard sucralfate up to 4.00 pH
elevation at dose level of 400 mg/kg of bodyweight.
77. The method as claimed in claim 1 wherein, CG provides increase
gastric juice secretion up to 5.9 ml induced by 50% ethanol
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 5.0 ml gastric juice
secretion at dose level of 50 mg/kg of bodyweight in comparison
with the reference standard omeprazole up to 3.5 ml gastric juice
secretion at dose level of 30 mg/kg of bodyweight and comparison
with the reference standard sucralfate up to 4.00 ml gastric juice
secretion at dose level of 400 mg/kg of bodyweight.
78. The method as claimed in claim 1 wherein, CG provides reduction
in acidity level up to 41.33 m Eg induced by 50% ethanol ulceration
at dose level of 25 mg/kg of bodyweight in comparison with
reference standard ranitidine up to 26.74 m Eg mean level of
reduction in acidity at dose level of 50 mg/kg of bodyweight, in
comparison with the reference standard omeprazole up to 32.01 m Eg
mean level of reduction in acidity at dose level of 30 mg/kg of
bodyweight and in comparison with the reference standard sucralfate
up to 52.00 m Eg mean level of reduction in acidity at dose level
of 400 mg/kg of bodyweight.
79. The method as claimed in claim 1 wherein, CGL provides gastric
mucosal protection up to 62.5% induced by 50% ethanol ulceration at
dose level of 25 mg/kg of bodyweight in comparison with reference
to the standard ranitidine up to 61.26% gastric mucosal protection
at dose level of 50 mg/kg of bodyweight in comparison with the
reference to standard omeprazole up to 67.5% gastric mucosal
protection at dose level of 30 mg/kg of bodyweight and in
comparison with the reference to standard sucralfate up to 87.5%
gastric mucosal protection at dose level of 400 mg/kg of
bodyweight.
80. The method as claimed in claim 1 wherein, CGL provides
elevation pH up to 3.9 induced by 50% ethanol ulceration at dose
level of 25 mg/kg of bodyweight in comparison with reference
standard ranitidine up to 4.96 pH elevation at dose level of 50
mg/kg of bodyweight in comparison with the reference standard
omeprazole up to 4.65 pH elevation at dose level of 30 mg/kg of
bodyweight and comparison with the reference standard sucralfate up
to 4.00 pH elevation at dose level of 400 mg/kg of bodyweight.
81. The method as claimed in claim 1 wherein, CGL provides increase
gastric juice secretion up to 4.6 ml induced by 50% ethanol
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 5.0 ml gastric juice
secretion at dose level of 50 mg/kg of bodyweight in comparison
with the reference standard omeprazole up to 3.5 ml gastric juice
secretion at dose level of 30 mg/kg of bodyweight and comparison
with the reference standard sucralfate up to 4.00 ml gastric juice
secretion at dose level of 400 mg/kg of bodyweight.
82. The method as claimed in claim 1 wherein, CGL provides
reduction in acidity level up to 39 m Eg induced by 50% ethanol
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 26.74 m Eg mean level of
reduction in acidity at dose level of 50 mg/kg of bodyweight, in
comparison with the reference standard omeprazole up to 32.01 m Eg
mean level of reduction in acidity at dose level of 30 mg/kg of
bodyweight and in comparison with the reference standard sucralfate
up to 52.00 m Eg mean level of reduction in acidity at dose level
of 400 mg/kg of bodyweight.
83. The method as claimed in claim 1 wherein, CG provides marked
gastric mucosal protection up to 50.25% induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
84. The method as claimed in claim 1 wherein, CG provides elevation
pH up to 3.5 induced by pylorus ligated ulceration at dose level of
25 mg/kg of body weight in comparison with reference standard
ranitidine up to 4.75 pH elevation at dose level of 50 mg/kg of
bodyweight.
85. The method as claimed in claim 1 wherein, CG provides increase
in gastric juice secretion up to 1.5 ml induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 1.82 ml gastric juice
secretion at dose level of 50 mg/kg of bodyweight.
86. The method as claimed in claim 1 wherein, CG provides reduction
in acidity level up to 44.33 m Eg induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 31.8 m Eg mean level of
reduction in acidity at dose level of 50 mg/kg of bodyweight.
87. The method as claimed in claim 1 wherein, CGL provides marked
gastric mucosal protection up to 60.17% induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference to the standard ranitidine up to 78.39% gastric
mucosal protection at dose level of 50 mg/kg of bodyweight.
88. The method as claimed in claim 1 wherein, CGL provides
elevation pH up to 3.08 induced by pylorus ligated ulceration at
dose level of 25 mg/kg of body weight in comparison with reference
standard ranitidine up to 4.75 pH elevation at dose level of 50
mg/kg of bodyweight.
89. The method as claimed in claim 1 wherein, CGL provides increase
in gastric juice secretion up to 4.83 ml induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 1.82 ml gastric juice
secretion at dose level of 50 mg/kg of bodyweight.
90. The method as claimed in claim 1 wherein, CGL provides
reduction in acidity level up to 40 m Eg induced by pylorus ligated
ulceration at dose level of 25 mg/kg of bodyweight in comparison
with reference standard ranitidine up to 31.8 m Eg mean level of
reduction in acidity at dose level of 50 mg/kg of bodyweight.
91.-96. (canceled)
Description
[0001] This invention relates to identification of Oroxylum
indicum, Indian medicinal plant as a rich source for flavanoid
compounds. We have identified mucoprotective and antigastric ulcer
properties in the flavone class of compounds. The invention also
provides a flavanoids mixture obtained in substantial yield from
hexane and acetone extracts. The hexane extract was fractionated,
purified and the compounds identified as Oroxylin A, Chrysin and
Baicalein. The acetone extract was purified and the compounds
identified as methoxy chrysin, Oroxyloside methyl ester and
chrysin-7-O-methyl glycoside. Invention of potent antigastric-ulcer
compounds were accompanied with synthesis of few analogues derived
from the oroxylin and chrysin, which were isolated from this plant
in good yields. As per the results, oroxyloside methyl ester
compound showed potent activity against gastric ulcers induced by
aspirin, ethanol, stress and pylorus ligation.
[0002] Gastric or peptic ulcer constitutes a major disease that
affects human gastrointestinal tract and major health problem both
in terms of morbidity and mortality. The common clinical features
of peptic ulcers are hyperacid secretion and ulcer formation in the
stomach and duodenal part of the intestine. Peptic ulcer disease
(PUD) primarily effects the adult population in developed and
developing countries. The risk for peptic ulcer was highest in
generations born before the turn of the century and has declined in
all subsequent generations. Low family income, old age, smoking
lower educational attainment, ethnicity, increased gastric acid
output, Helicobacter pylori, NSAIDs and stress are that act as
significant and independent basic risk factors in PUD risk factor.
The prevalence of upper GI diseases is increasing in subjects aged
65 years and over. Almost 40% of GU (gastric ulcer) and 25% of DU
(duodenal ulcer) in the elderly patients are associated with the
use of non-steroidal anti-inflammatory drugs (NSAIDs).
Gastrointestinal (GI) side effects include ulcers (found at
endoscopy in 15-30% of patients using NSAIDs regularly),
complications such as upper GI bleeding (annual incidence of
1.0-1.5%) and development of upper GI symptoms such as dyspepsia
(occurring in up to 60% patients taking NSAIDs). NSAIDs are among
most widely used prescribed drugs world wide for anti-inflammatory,
analgesic and antipyretic effects, whereas low dose aspirin (also a
NSAID) is used for cardiovascular prophylaxis. Although the
therapeutic benefits of these drugs are substantial, their use is
limited by their gastroduodenal toxicity, some of which can be
serious or even fatal. Established risk factors for NSAIDs induced
GI complications are age, ulcer history, heavy alcohol consumption,
individual NSAIDs, dose association with corticoid or aspirin or
anticoagulant (ulcer heamorrhage). The therapeutical acquisition of
PUD of the year 2004 is the use of COX-2 inhibitors reduced
significantly the GI side effects of anti-inflammatory treatments.
Since cardiac adverse effects of certain COX-2 inhibitors (NSAIDs)
had been reported, the treatments with COX-2 inhibitors came widely
into question. Aspirin is a very useful medication for the
prevention of cardiovascular thrombotic events in patients with or
those at risk for cardiovascular disease (CVD). Patients being
treated with aspirin, even at 81 mg/day for cardioprotection,
should be assessed for factors that increase the risk for GI
injury.
[0003] Stress has wide spread effects on various body systems.
Stress has long been implicated as one of the risk factors for
coronary diseases. Stress, defined as an acute threat to
homeostasis, evokes an adaptive or allostatic response and can have
both a short and long term influence on the function of the
gastrointestinal tract. Stress ulceration of the stomach is
associated with clinical conditions like trauma, head injury,
burns, shock, sepsis and neurological disorders; and is now
regarded as a multifactorial phenomenon. It is reported to result
from interaction between mucosal, vascular and neuro-humoral
factors and the autonomic nervous system plays a crucial role.
Circulatory disturbances and the nutritional deficiency are thus
induced in the local tissue, which are then followed by a rapid
appearance of a deep ulcer.
[0004] Gastrointestinal complications frequently occur in patients
admitted to the intensive care unit. Of this ulceration and
bleeding related to stress-related mucosal disease can lengthen
hospitalization and increases mortality. The prophylactic regimen
chosen to prevent stress ulcer bleeding should take into account
the risk factors and underlying disease state of individual
patients to provide the best therapy to those most likely to
benefit.
[0005] Ethanol is common cause of acute gastric mucosal injury in
both human and animals. This gastritis may produce life-threatening
hemorrhage that requires surgical intervention. The mortality rate
of such an intervention is at least 30%. In the rat persistence of
gastric mucosal ischemia produces chronic ulceration of the
stomach. Several other factors are associated with ulcer formation
although this may be an indirect relationship such factors include
hereditary, smoking, elevated calcium level, corticosteroids in
high dose.
[0006] The majority of peptic ulcers causing growing burning or
aching pain in the region of the stomach made worse by or unrelated
to food. Pain tends to be worse at night and occurs usually 1 to 3
hours after food during the day. Additionally there may be food
aversion, weight loss, nausea, belching or bloating. There is great
individual variation and occasionally the pain may be referred to
the back or the upper quadrant of the abdomen. Complications
include bleeding, obstruction, perforation or intractable pain.
Prophylactic options for patients suffering with gastrointestinal
ulceration include antacids, sucralfate, histamine2-receptor
antagonists (H2RAs), prostaglandins, muscarinic M1-antagonists and
proton pump inhibitors. Therapy has been and still is largely
empirical.
[0007] The prostaglandin's fulfilled their early promise and
muscarinic M.sub.1-antagonists, although more selective than the
earlier anti-cholinergic agents, have limited application.
Inhibition of the H.sup.+/K.sup.+ ATPase by non-competitive agents
is limited to short-term administration and the development of a
potent selective gastrin antagonist is yet be realized.
[0008] Reduction of symptoms, nullifying the side effects and
improvement in quality of life are among the top priorities of
diseases for the suffering persons. Although these factors need to
be considered and balanced in evaluating new therapies for
widespread use. The reduction in risk in a specific patient
population should be considered before a particular regimen is
deemed ineffective or too costly.
[0009] The plants create unexpected and novel structure to protect
themselves from predator organism. By trail and error, several
plants and plant products are identified as drugs. Natural product
drugs although are highly effective and free from toxic side
effects, have a disadvantage with respect to short supply and
chemical structure, which makes their manufacture difficult or
impossible. Natural product drugs have been a source of lead
structure in drug design and development. Semi synthetic analogues
or synthetic analogues closely related to the natural product drug
of lead are synthesized and screened to disorder their action. In
the light of above descriptions, in our isolation work flavonoids
have been isolated which are potent antiulcer agents increasing the
gastric pH, mucosal lining of stomach and related disorders, led to
the identification of Oroxylum indicum, which contained in
substantial yields potent antiulcer flavonoids for the first
time.
[0010] Oroxylum indicum Vent has been advocated in traditional
medical practice of India for several diseases. In folklore
medicine in India, the powdered stem bark is used to treat
dysentery, diarrhea, sore throat, cough and bone fractures (Kausik,
P and Dhaman A. K, The medicinal plants and crude drugs of India,
2000, 398).
[0011] The main object of the invention is to examine and assess
the relation between plant-originated substances and their
bioactivity measured in terms of cytoprotective and antigastric
ulceric activities and to determinate if these effects are capable
of affecting the gastric mucosal lesions induced by absolute
ethanol, cold stress, aspirin and pylorus ligated.
[0012] Another object of the invention is to assign new activity as
anti ulcer compounds Oroxylin A, Chrysin, Baicalein, methoxy
chrysin, Oroxyloside methyl ester and chrysin-7-O-methyl glucoside,
isolated form either hexane extract or the acetone extract of
Oroxylum indicum and synthetic analogues form Oroxylin A and
chrysin. Further, these isolated and synthetic compounds are used
for therapeutically for control of ulcer and other like
diseases.
[0013] The present invention also relates to activity of these
compounds and oroxyloside methyl ester (new compound) and another
two compounds namely methoxy chrysin and chrysin-7-O-methyl
glucoside as first time isolated form this plant Oroxylum indicum.
All synthetic analogues prepared in the present invention is also
new synthetic compounds. This invention further identified a first
time anti ulcer activity using these compounds
[0014] In accordance with the objects of this invention the present
invention identified a new source namely Oroxylum indicum dried
stem bark possessing substantial yields and compounds have the
activity against gastric ulcer. This invention identifies presence
of isolated compounds Oroxylin A, Chrysin, Baicalein, methoxy
chrysin, Oroxyloside methyl ester and chrysin-7-O-methyl glucoside
and synthetic analogs of oroxylin-A as a acyl ester derivatives and
alkyl amino derivatives of chrysin.
[0015] The present invention also identifies for the first time
oroxyloside methyl ester as new naturally occurring compound from
acetone extract of Oroxylum indicum.
[0016] In another embodiment of the invention compound methoxy
chrysin is isolated for the first time from acetone extract of
Oroxylum indicum.
[0017] Still another embodiment of the present invention provides
process for the isolation of Oroxylin A, Chrysin, Baicalein,
methoxy chrysin, Oroxyloside methyl ester and chrysin-7-O-methyl
glycoside as anti ulcer compounds form Oroxylum indicum the said
process comprised following steps (1) hexane extract, (2) acetone
extract. [0018] a) extraction of dried stem bark of Oroxylum
indicum with hexane by using Soxhlet apparatus [0019] b) extract
was filtered to afford solid separate out [0020] c) subjecting the
residue to a first elution with 1% methanol in chloroform to obtain
Oroxylin A and [0021] d) subjecting the residue (step c) to a
second elution with 2% methanol in chloroform to obtain Chrysin and
[0022] e) subjecting the residue (step d) to a third elution with
3% methanol in chloroform to obtain Baicalein
[0023] A further object of the invention relates to the isolation
of these three compounds namely Oroxylin-A, Chrysin and Baicalein
from Oroxylum indicum with hexane extract.
[0024] Further more all these compounds isolated from Oroxylum
indicum shows anti-ulcer activity for the first time.
[0025] Further more extraction of dried stem bark of Oroxylum
indicum with acetone, and process for isolation of compounds along
with Oroxylin A, Chrysin and Baicalein, compounds Methoxy chrysin
and Oroxyloside methyl ester and chrysin-7-O-methyl glycoside the
said process comprising steps of [0026] a) subsequent extraction
with acetone of the hexane extracted material by the same procedure
to obtain the residue [0027] b) subjecting the residue to a first
elution with 1% methanol in chloroform to obtain Oroxylin A and
[0028] c) subjecting the residue (step b) to a second elution with
2% methanol in chloroform to obtain Chrysin and [0029] d)
subjecting the residue (step c) to a third elution with 3% methanol
in chloroform to obtain Baicalein [0030] e) subjecting the residue
(step d) to fourth elution with 4% methanol in chloroform to obtain
Methoxy chrysin [0031] f) subjecting the residue (step e) to a
fifth elution with 5% methanol in chloroform to obtain Oroxyloside
methyl ester [0032] g) subjecting the residue (step f) to a sixth
elution with 7% methanol in chloroform to obtain chrysin-7-O-methyl
glycoside.
[0033] Further invention identifies that in above said process
compound Oroxyloside methyl ester was identified as first isolated
natural compound and compounds methoxy chrysin and
chrysin-7-O-methyl glycoside identified as a first time isolated
compounds form this plant Oroxylum indicum, and the compound
Oroxyloside methyl ester shows excellent potent molecule for the
antiulcer activity and compound chrysin-7-O-methyl glycoside shows
very good activity against gastric ulcer.
[0034] Present invention relates to the identification of isolation
of potent antiulcer molecules from extracts of Oroxylum indicum,
which may find preventive as well as therapeutic applications for
the control of gastrointestinal toxicity along with other
complications further use in disorders where gastrointestinal
toxicity inhibition play an important role in prevention and
treatment of diseases not mentioned in this description.
[0035] The present invention relies on the identification of
Oroxylum indicum an Indian medicinal plant as possessing potent
where gastrointestinal toxicity inhibitors. The hexane extract of
dried stem bark of Oroxylum indicum constitutes 95% of three major
active principles identified as Oroxylin A, Chrysin, Baicalein and
acetone extract contains six major active principles, that contains
apart from Oroxylin A, Chrysin, Baicalein and compounds namely
methoxy chrysin, Oroxyloside methyl ester and chrysin-7-o methyl
glycoside and synthesized analogues of Oroxylin, Chrysin in
substantial yields. These mixtures and molecules may find
preventive as well as therapeutic application in controlling
disorders of gastrointestinal disorders and diseases.
[0036] These antigastric ulcer molecule(s) may be administrated by
any suitable conventional method prevalent in pharmaceutical
practice for the treatment of gastrointestinal toxicity, control
gastric pH and reduction ulcers risk factors in GI toxicity, and
also in disease condition such as inflammation, stress conditions,
NSAID therapy requiring inhibition of gastric acid output,
formation of mucosal lining, elevate the gastric acid pH for
prevention and treatment of diseases mentioned and not mentioned in
this invention.
[0037] The potent antiulcer OA-5 molecule in this invention
antagonize the aggressive factors, which play in the pathogenesis
of gastric lesions and augment defensive factors to protect the
gastric mucosal from injury. Application as the case of antigastric
ulcer molecules may preferably be taken orally and potentiate the
mechanism of action and hence impart better therapeutic action. The
antigastric ulcer molecules present in pharmaceutical preparation
in this invention may be formulated with any of the suitable
pharmaceutically acceptable additive, carrier, vehicle, food
preparations etc., suitable for human application. The materials
should be selected such that they should not interfere with the
potency and the property of the mixture or the molecule but
materials that can add to or improve the activity, are preferred
and can decided by the conventional art and the skills available in
formulary.
Effective dose:
[0038] Effective dose level and duration of drug administration may
be decided by the skill of ordinary art in order to bring
therapeutic parameter of the disease under consideration under the
control. The actual rate, amount of applications, and the time of
administration may vary depending upon the disease condition and
severity and may be irrespective of the concentration and duration
as described in the examples of this invention.
Synthesis of 7-O-acyl derivatives of Oroxylin A:
##STR00001##
[0039] Procedure: The corresponding acid, EDCI (0.836 mmol) and
HOBt (0.69 mmol) were cooled to 0.degree. C. and stirred in
anhydrous methylene chloride (5 ml) for 15-30 min under nitrogen
atmosphere. To this mixture, Oroxylin A (0.704 mmol) in anhydrous
N,N-dimethylformaldehye (3 ml) was added. The entire reaction
mixture was stirred at room temperature for 4-5 h under nitrogen.
After completion of the reaction (TLC), the reaction mixture was
poured into ice water and washed with methylene chloride
(2.times.10 ml). The combined organic layers were dried over
anhydrous sodium sulphate and concentrated under vacuum. Residue
was purified by column chromatography on silica gel (60-120 mesh)
to give corresponding 7-O-acyl derivatives of Oroxylin A ORPM-1 and
ORC-16 in good yields.
Preparation of alkyl amino derivatives of chrysin:
##STR00002##
General procedure for the preparation of 7-O-alkylamino derivatives
of Chrysin: i) General procedure for the preparation of 7-O-alkyl
derivatives of chrysin:
[0040] To a mixture of chrysin 1 (1 g, 3.93 mmol) and anhydrous
potassium carbonate (0.81 g, 5.8 mmol) in 20 ml acetone,
corresponding dibromoalkane (1,3-dibromo propane for 2a, 1,
4-dibromo butane for 2b. The mixture was refluxed under nitrogen
atmosphere for 3-4 h. After completion of the reaction potassium
carbonate was filtered and washed with excess of acetone
(2.times.50 ml). The combined acetone layers are concentrated under
vacuum. The residue was purified by column chromatography on silica
gel (60-120 mesh) to yield 7-O-bromoalkyl chrysin (2a, 2b) in pure
form.
ii) General procedure for the preparation of 7-O-alkyl amino
derivatives of chrysin:
[0041] To a mixture of bromoalkyl chrysin (2a, 2b) and anhydrous
potassium carbonate (2.41 g, 17.2 mmol) in 20ml acetonitrile,
corresponding amine was added. The mixture was refluxed under
nitrogen atmosphere for 3-4 h. After completion of the reaction,
the reaction mixture was brought to room temperature and was poured
into ice water and washed with methylene chloride (2.times.10 ml).
The combined organic layers were dried over anhydrous sodium
sulphate and concentrated under vacuum. The residue was purified by
column chromatography on silica gel (60-120mesh) to give the
corresponding 7-O-alkylamino derivatives of chrysin in very good
yields (60-80%).
Preparation glycoside derivatives of flavanoids:
##STR00003##
Procedure: 1) Acetic anhydride (2.5 ml) was added to a solution of
anhydrous D-glucose (1.0 g, 5.55 mmol) in 5 ml of pyridine and
stirred at RT for 8 hrs. The solution was evaporated in vacuo, the
syrupy residue dissolved in 25 ml of CHCl.sub.3 and washed with
water, saturated Na.sub.2SO.sub.4 and evaporated in vacuo gives
2,3,4,6 penta-O-acyl-D-galacto pyronose (2) with out further
purification the yield is 92%. 2). A solution of Hydrogen bromide
in glacial acetic acid (40%, 5ml) was added to a stirred solution
of (2) (1.17 g, 3.0 mmol) in 10 ml of acetic acid. Stirring was
continued at RT for 8 hrs, kept away form direct sunlight. The
reaction mixture is carefully poured in to 50 ml of ice water and
extracted with three times with CHCl.sub.3. The combine layers are
washed with saturated Na.sub.2SO.sub.4 solution and NaCl solution
and evaporated in vaccuo and this yellow syrupy residue is
dissolved in 5 ml of ether and allowed to crystallize at 5.degree.
c and resultant compound was gives the aceto bromo galactose (3)
yield was 72%. 3). Take the corresponding flavonoid (2.43 mmol)
dissolved in acetone and add anhydrous K.sub.2CO.sub.3 (0.4 g,
2.916 mmol) and stirrer for 15 min then add acetobromogalactose (3)
(1 g, 2.43 mmol) and stirrer at RT for 3-4 hrs. After completion of
reaction filter the reaction mixture and evaporated in vacuo,
purify with column chromatography and yielded 5a and 5b 85-90%. 4)
To a solution of 5a and 5b in methanol add methanolic KOH and
stirred for 1-2 hrs and after completion of reaction, evaporate the
methanol completely dissolved the reaction mixture in water and
extracted with CHCl.sub.3 two times and combine layers dried over
Na.sub.2SO.sub.4 and evaporated in vacuo gives 6a and 6b in pure
form without further purification. Yield 95%. 6). Preparation of
OA-5 Acid (7-O-glucoronide derivative of Oroxylin A):
##STR00004##
Procedure: Compound dissolved in methanolic KOH and reflux for
1-2hrs. After completion of reaction (monitored by TLC), methanol
completely dissolved the reaction mixture in water and extracted
with ethyl acetate two times and combine layers dried over
Na.sub.2SO.sub.4 and evaporated in vacuo gives corresponding acid
on column chromotogarphy. Yield: 85%.
[0042] In the following structures,
[0043] FIG. 1 represents formula of Oroxylin-A
[5,7-Dihydroxy-6-methoxy-2-phenylchromen-4-one]
[0044] FIG. 2 represents formula of Chrysin
[5,7-dihydroxy-2-phenyl-chromen-4-one]
[0045] FIG. 3 represents formula of Baicalein
[5,6,7-trihydroxy-2-phenyl-chromen-4-one]
[0046] FIG. 4 represents formula of Methoxy chrysin
[5-hydroxy-7-methoxy-2-phenyl-chromen-4-one]
[0047] FIG. 5 represents formula of Oroxoloside methyl ester
[3,4,5-trihydroxy-6-(6-methoxy-4-oxo-2-phenyl-4-H-chromen-7-yoloxy)
tetrahydro-pyran-2-carboxylicacid methyl ester]
[0048] FIG. 6 represents formula of chrysin-7-O-methyl glycoside
[3,4,5-trihydroxy-6-(4-oxo-2-phenyl-4-H-chromen-7-yoloxy)
tetrahydro-pyran-2-carboxylicacid methyl ester]
[0049] FIG. 7 represents formula of ORC-16 [Heptadecanoic acid
5-hydroxy-6-methoxy-4-oxo-2-phenyl-4H-chromen-7-yl ester]
[0050] FIG. 8 represents formula of ORPM-1 [4-methyl-benzoic acid
5-hydroxy-6-methoxy-4-oxo-2-phenyl-4-H-chromen-7-yl ester]
[0051] FIG. 9 represents formula CPP-2
[5-Hydroxy-2-phenyl-7-(3-piperidin-1-yl-propoxy)-chromen-4-one]
[0052] FIG. 10 represents formula of CHM-2
[5-Hydroxy-7-(3-morpholin-4-yl-propoxy)-2-phenyl chromen-4-one]
[0053] FIG. 11 represents formula of CHN-2 [7-(3-Dimethyl
amino-propoxy)-5-hydroxy-2-phenyl chromen-4-one]
[0054] FIG. 12 represents formula of NMC-2
[5-Hydroxy-7-[3-(4-methyl-piperzin-1-yl]-propoxy)-2-phenyl
chromen-4-one]
[0055] FIG. 13 represents formula of NMC-3
[5-Hydroxy-7-[4-(4-methyl-piperzin-1-yl]-butoxy)-2-phenyl
chromen-4-one]
[0056] FIG. 14 represents formula of CHM-3
[5-Hydroxy-7-(4-morpholin-4-yl-butoxy)-2-phenyl chromen-4-one]
[0057] FIG. 15 represents formula of OAG
[5-Hydroxy-6-methoxy-2-phenyl-7-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahy-
dro-pyran-2-yloxy)-chromen-4-one]
[0058] FIG. 16 represents formula of CG
[5-Hydroxy-2-phenyl-7-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran--
2-yloxy)-chromen-4-one]
[0059] FIG. 17 represents formula of OA-5 Acid
[3,4,5-Trihydroxy-6-(5-hydroxy-6-methoxy-4-oxo-2-phenyl-4H-chromen-7-ylox-
y)-tetrahydro-pyran-2-carboxylic acid].
##STR00005## ##STR00006## ##STR00007##
[0060] In another embodiment of the invention of Oroxylin A (FIG.
1) obtained from Oroxylum indicum has the following spectrochemical
and physical properties MP: 231-232.degree. C. IR (KBr)v.sub.max
3435, 2825, 1622, 1016 cm.sup.-1. .sup.1H NMR (200 MHz, CDCl.sub.3+
MeOH-d.sub.4) (.delta.) 7.82-7.86 (2H, m, H-2', 6'), 7.42-7.56 (3H,
m, H-3', 4', 5'), 6.62 (1H, s, H-8), 6.58 (1H, s, H-3), 3.96 (3H,
s, Ar-OMe). .sup.13C NMR (50 MHz, DMSO d.sub.6) .delta. 163.37
(C-2), 104.46 (C-3), 182.31 (C-4), 152.64 (C-5),130.80 (C-6),
157.62 (C-7), 94.49 (C-8), 152.79 (C-9), 104.71 (C-10), 131.60
(C-1'), 126.42 (C-2'), 129.20 (C-3'), 132.06 (C-4'), 60.06 (OMe).
EIMS:284 (M.sup.+, 100).
[0061] In another embodiment of the invention of Chrysin (FIG. 2)
obtained from Oroxylum indicum has the following spectral chemical
and physical properties MP: 285-286.degree. C. IR (KBr)v.sub.max
3450, 2925, 1626, 1024 cm.sup.-1. .sup.1H NMR (400 MHz, CDCl.sub.3+
MeOH-d.sub.4) (.delta.) 7.82-7.92 (2H, m, H-2', 6'), 7.44-7.58 (3H,
m, H-3', 4', 5'), 6.64 (1H, s, H-8), 6.44 (1H, s, H-3), 6.24 (1H,
s, H-6). .sup.13C NMR (50 MHz, DMSO d.sub.6) .delta.163.0 (C-2),
105.0 (C-3), 181.6 (C-4), 161.5 (C-5), 99.0 (C-6), 164.3 (C-7),
94.0 (C-8), 157.3 (C-9), 104.0 (C-10), 138.7 (C-1'), 126.1 (C-2'),
128.8 (C-3'), 131.6 (C-4'), 128.8 (C-5'), 126.1 (C-6'). EIMS:
M.sup.+254.
[0062] In another embodiment of the invention of Baicalein (FIG. 3)
obtained from Oroxylum indicum has the following spectral chemical
and physical properties MP: 223-226.degree. C. .sup.1H NMR (400
MHz, CDCl.sub.3+ MeOH-d.sub.4) (.delta.) 7.82-7.98 (2H, m, H-2',
6'), 7.44-7.60 (3H, m, H-3', 4', 5'), 6.62 (1H, s, H-8), 6.58 (1H,
s, H-3). .sup.13C NMR (50 MHz, DMSO d.sub.6) .delta.162.9 (C-2),
104.5 (C-3), 182.1 (C-4), 147.0 (C-5), 129.3 (C-6), 153.7 (C-7),
94.0 (C-8), 149.9 (C-9), 104.3 (C-10), 131.0 (C-1'), 126.2 (C-2'),
129.0 (C-3'), 131.7 (C-4'), 129.0 (C-5'), 126.2 (C-6). EIMS:270
(M.sup.+, 100).
[0063] In another embodiment of the invention of Methoxy chrysin
(FIG. 4) obtained from Oroxylum indicum has the following spectral
chemical and physical properties MP: 164.degree. C. (KBr)v.sub.max
3450, 2925, 1654, 1621, 1016 cm.sup.-1. .sup.1NMR (200 MHz,
CDCl.sub.3) (.delta.)13.0(1H, s, OH-5), 7.82-7.96 (2H, m, H-2',
6'), 7.44-7.60 (3H, m, H-3', 4', 5'), 6.62 (1H, s, H-8), 6.60 (1H,
s, H-3), 6.58 (1H, s, H-6), 3.96 (3H, s, OMe). .sup.13C NMR (300
MHz, CDCl.sub.3) (.delta.)164.08 (C-2), 105.04 (C-3), 182.88 (C-4),
164.08 (C-5), 93.97 (C-6), 153.31 (C-7), 93.97 (C-8), 153.31(C-9),
105.50 (C-10), 130.96 (C-1'), 126.24 (C-2'), 128.88 (C-3'), 131.26
(C-4'), 128.88 (C-5'), 126.24 (C-6'), 60.63 (Ar-OMe). EIMS:192
(M.sup.30 , 100).
[0064] In another embodiment of the invention of Oroxyloside methyl
ester (FIG. 5) obtained from Oroxylum indicum has the following
spectral chemical and physical properties MP: 201.degree. C. UV
.lamda..sub.max (MeOH)345, 285 nm. IR (KBr)v.sub.max 3395, 2924,
1735 (ester-C.dbd.O), 1618 (--C.dbd.O), 1461, 1359, 1224, 1076
cm.sup.-1, .sup.1H NMR (200 MHz, DMSO-d.sub.6) (.delta.) 12.78 (1H,
s, OH-5), 7.90-8.0 (2H, m, H-2', 6'), 7.48-7.60 (3H, m, H-3', 4',
5'), 6.84 (1H, s, H-8), 6.80(1H, s, H-3), 3.4-5.50 (m, sugar
protons), 3.78 (3H, s, OMe), 3.82 (3H, s, Ar-OMe). .sup.13C NMR
(300 MHz, DMSO-d.sub.6) (.delta.) 163.72 (C-2), 104.95 (C-3),
182.37 (C-4), 152.52 (C-5), 132.04 (C-6), 156.08 (C-7), 94.07
(C-8), 152.17 (C-9), 106.12 (C-10), 130.59 (C-1'), 126.35
(C-2',6'), 129.03 (C-3',5'), 132.06 (C-4'), 99.49 (C-1''),75.60
(C-2''), 75.25 (C-3''), 72.77 (C-4''), 71.18 (C-5''), 168.96
(C-6''), 60.21 (Ar-OMe), 51.81 (OMe). EIMS: 475 (M.sup.+1,
100).
[0065] In another embodiment of the invention of Chrysin-7-O-methyl
glycoside (FIG. 6) obtained from Oroxylum indicum has the following
spectral chemical and physical properties MP: 201.degree. C. UV
.lamda..sub.max, (MeOH)345, 285 nm. IR (KBr)v.sub.max 3390, 2928,
1735 (ester-C.dbd.O), 1610 (--C.dbd.O), 1465, 1345, 1210, 1055
cm.sup.-1. .sup.1H NMR (200 MHz, DMSO-d.sub.6) (.delta.) 12.70(1H,
s, OH-5), 7.92-8.05 (2H, m, H-2', 6'), 7.45-7.56 (3H, m, H-3', 4',
5'), 6.80 (1H, s, H-8),6.74 (1H, s, H-6) 6.68(1H, s, 3.4-5.50 (m,
sugar protons), 3.70(3H, s, OMe). .sup.13C NMR (300 MHz,
DMSO-d.sub.6) (.delta.) 162.65 (C-2), 104.64 (C-3), 181.97 (C-4),
152.05 (C-5), 98.56 (C-6), 155.60 (C-7), 94.23(C-8), 151.87 (C-9),
106.10 (C-10), 131.59 (C-1'), 126.05 (C-2',6'), 129.15 (C-3',5'),
132.00 (C-4'), 99.43 (C-1''),75.45 (C-2''), 75.05 (C-3''), 72.54
(C-4''), 70.98 (C-5''), 168.90 (C-6''), 51.81 (OMe). EIMS: 445
(M.sup.++1)
[0066] In another embodiment of the invention of synthetic
analogues from oroxylin-A obtained from Oroxylum indicum as acyl
derivatives namely 7-O-dodecyl oroxylin A (FIG. 7) the following
spectral chemical and physical properties MP: 101.2.degree. C.;
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta.12.82 (1H, s, OH-5),
7.88-7.92 (2H, m, H-2', 6'), 7.50-7.56 (3H, m, H-3', 4', 5'), 6.70
(1H, s, H-8), 6.64 (1H, s, H-3), 3.90 (3H, s, OMe), 2.62 (2H, t,
H-2''), 1.60-1.80 (2H, m, H-3''), 1.22-1.40 (16H, brs,
H-4''-H-11''), 084 (3H, t, H-12''). FABMS: 467 (M.sup.++1).
[0067] In another embodiment of the invention of synthetic
analogues from oroxylin-A obtained from Oroxylum indicum as acyl
derivatives named 7-O-(p-methylbenzoyl) oroxylin A (FIG. 8) the
following spectral chemical and physical properties MP: 203.degree.
C., .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 12.82 (1H, s, OH-5),
8.46 (2H, d, J=6Hz, H-2'', 6''), 7.82-7.84 (2H, m, H-2', 6'),
7.50-7.58 (3H, m. H-3', 4', 5'), 7.36 (2H, d, J 6 Hz, H-3'', 5''),
6.90 (1H, s, H-8), 6.70 (1H, s, H-3), 3.96 (3H, s, OMe), 2.52 (3H,
s, Ar-Me). FABMS: 429 (M.sup.++Na).
[0068] In another embodiment of the invention of synthetic
analogues from chrysin obtained from Oroxylum indicum as alkyl
amino derivatives 7-O-propyl (piperidinyl) Chrysin (FIG. 9) the
following spectral-chemical and physical properties: MP:
215.degree. C., .sup.1 NMR (300 MHz, CDCl.sub.3) .delta.12.50 (1H,
s, OH-5), 7.82-7.86 (2H, m, H-2', 6'), 7.44-7.58 (3H, m, H-3', 4',
5'), 6.66 (1H, s, H-8), 6.58 (1H, s, H-3), 6.39 (1H, s, H-6), 4.16
(2H, t, H-1''), 2.38-2.58 (6H, m, H-2''', 6''' and H-3''),
1.98-2.08 (2H, H-2''), 1.58-1.60 (4H, m, H-3''', 5'''), 1.41-1.50
(2H, m, H-4'''). FABMS: 402(M.sup.++Na).
[0069] In another embodiment of the invention of synthetic
analogues from chrysin obtained from Oroxylum indicum as alkyl
amino derivatives 7-O-propyl (morphinyl) chrysin (FIG. 10) the
following spectral chemical and physical properties: MP:
138.degree. C., .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.12.60 (1H,
s, OH-5), 7.86-7.90 (2H, m, H-2', 6'), 7.50-7.62 (3H, m, H-3', 4',
5'), 6.64 (1H, s, H-8), 6.46 (1H, s, H-3), 6.38 (1H, s, H-6), 4.18
(2H, t, H-1''), 3.82 (4H, t, H-3''', 5'''), 2.40-2.60 (6H, m,
H-2''', 6''', H-3''), 1.9-2.10 (2H, m, H-2''). FABMS: 382
(M.sup.++1).
[0070] In another embodiment of the invention of synthetic
analogues from chrysin obtained from Oroxylum indicum as alkyl
amino derivatives 7-O-propyl (N,N-Dimethyl) chrysin (FIG. 11) the
following spectral chemical and physical properties: MP
119-120.degree. C. , .sup.1 H NMR (400 MHz, CDCl.sub.3) 67 12.72
(1H, s, OH-5), 7.82-7.86 (2H, m, H-2', 6'), 7.50-7.58 (3H, m, H-3',
4', 5'), 6.64 (1H, s, H-8), 6.48 (1H, s, H-3), 6.38 (1H, s, H-6),
4.10 (2H, t, H-1''), 2.42 (2H, H-3''), 2.22 (6H, s, 2.times.Me),
1.98-2.02 (2H, m, H-2''). FABMS: 340 (M.sup.++1)
[0071] In another embodiment of the invention of synthetic
analogues from chrysin obtained from Oroxylum indicum as alkyl
amino derivatives 7-O-propyl (N-methyl piperizinyl) chrysin (FIG.
12) the following spectral chemical and physical properties: MP:
128-130.degree. C., .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.70
(1H, s, OH-5), 7.84-7.86 (2H, m, H-2', 6'), 7.46-7.58 (3H, m, H-3',
4', 5'), 6.64 (1H, s, H-8), 6.52 (1H, s, H-3), 6.18 (1H, s, H-6),
4.12 (2H, t, H-1''), 2.40-2.60 (9H, m, H-3''', 5''', H-3'' and
H-2''', 6'''), 2.30 (3H, s, Me), 1.90-2.10 (2H, m, H-2''). FABMS:
395 (M.sup.++1).
[0072] In another embodiment of the invention of synthetic
analogues from chrysin obtained from Oroxylum indicum as alkyl
amino derivatives 7-O-butyl (N-methyl piperizinyl) chrysin (FIG.
13) the following spectral chemical and physical properties: MP:
80.degree. C., .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 12.64 (1H,
s, OH-5), 7.76-7.86 (2H, m, H-2', 6'), 7.40-7.58 (3H, m, H-3', 4',
5'), 6.58 (1H, s, H-8), 6.40 (1H, s, H-3), 6.30 (1H, s, H-6), 4.0
(2H, t, H-1''), 2.80-3.0 (10H, m, H-2''', 6''', H-3''', 5''',
H-4''), 2.58 (3H, s, Me), 1.6-1.82 (4H, m, H-2'', 3''). FABMS: 431
(M.sup.++Na).
[0073] In another embodiment of the invention of synthetic
analogues from chrysin obtained from Oroxylum indicum as alkyl
amino derivatives 7-O-butyl (morphinyl) chrysin Chrysin (FIG. 14)
the following spectral chemical and physical properties MP:
130.degree. C., .sup.1 H NMR (300 MHz, CDCl.sub.3) .delta. 12.38
(1H, s, OH-5), 7.80-7.88 (2H, m, H-2', 6'), 7.50-7.58 (3H, m, H-3',
4', 5'), 6.72 (1H, s, H-8), 6.62 (1H, s, H-3), 6.40 (1H, s, H-6),
4.10 (2H, t, H-1''), 3.70-3.76 (4H, m, H-3''', 5'''), 2.40-2.50
(6H, m, H-2''', 6''', H-4''), 1.80-2.0 (2H, m, H-3'''), 1.60-1.80
(2H, m, H-2''). FABMS: 396 (M.sup.++1).
[0074] In another embodiment of the invention of synthetic
analogues from oroxylin A obtained from Oroxylum indicum as
glycoside derivatives OAG (FIG. 15) the following spectral chemical
and physical properties: .sup.1H NMR (200 MHz,
CDCl.sub.3+MeOH-d.sub.4) .delta.12.78 (1H, s, OH-5), 7.80-7.86 (2H,
m, H-2', 6'), 7.42-7.56 (3H, m, H-3', 4', 5'), 6.83 (1H, s, H-8),
6.50 (1H, s, H-3), 3.4-5.50 (m, sugar protons), 3.78 (3H, s, OMe),
3.92-3.96 (2H, d).
[0075] In another embodiment of the invention of synthetic
analogues from Chrysin obtained from Oroxylum indicum as glycoside
derivatives CG (FIG. 16) the following spectral chemical and
physical properties: .sup.1H NMR (200 MHz, CDCl.sub.3+MeOH-d.sub.4)
.delta.12.78 (1H, s, OH-5), 7.82-7.98 (2H, m, H-2', 6'), 7.44-7.60
(3H, m, H-3', 4', 5'), 6.63 (1H, s, H-8), 6.48(1H, s, H-3), 6.24
(1H, s, H-6), 3.4-5.50 (m, sugar protons), 3.90-3.93 (2H, d).
[0076] In another embodiment of the invention of synthetic
analogues from oroxyloside methyl ester obtained from Oroxylum
indicum as glycoside derivative OA-5 Acid (FIG. 17) the following
spectral chemical and physical properties: .sup.1H NMR (200 MHz,
MeOH-d.sub.4) (.delta.) 12.70 (1H, s, OH-5), 7.94-8.05 (2H, m,
H-2', 6'), 7.40-7.55 (3H, m, H-3', 4', 5'), 6.80 (1H, s, H-8), 6.57
(1H, s, H-3), 3,4-5.50 (m, sugar protons), 3.82 (3H, s,
Ar-OMe).
EXAMPLE 1
Experimental Protocol: Process of Isolation of Oroxylin A, Chrysin
and Baicalein
[0077] The dried powdered stem bark (200 g) was first defatted with
petrol in a soxlet apparatus. The bright yellow coloured powdered
solid was obtained after the filtration of the hexane extract. The
solid (2 g) was chromatographed over silica gel (60-120 mesh), 3.5
cm dia column loaded to a height of 60 cm. The column was
successively eluted with 1% methanol in chloroform to afford
Oroxylin-A. The yield of Oroxylin-A is around 1.2 g. Further
elution of the column with 2% methanol in chloroform afforded
chrysin. The yield of Chrysin is around 0.2 g. Further elution of
the column with 3% methanol in chloroform afforded Baicalein. The
yield of Baicalein is around 0.5 g.
Process of isolation of Methoxy chrysin, Oroxyloside methyl ester
and chrysin-7-O-methyl glycoside: The dried powdered stem bark (200
g) was successively extracted with hexane and acetone. The acetone
extract on evaporation afforded a dark brown colored residue (3 g).
The residue was chromatographed over silica gel (60-120 mesh), 3.5
cm dia column loaded to a height 60 cm. In addition to oroxylin A,
Chrysin and Baicalein two more compounds namely Methoxychrysin,
Oroxyloside methyl ester and chrysin-7-O-methyl gluconide were
isolated as follows. The column was successively eluted with 1%
methanol in chloroform to afford Oroxylin-A. The yield of
Oroxylin-A is around 0.2 g. Further elution of the column with 2%
methanol in chloroform afforded chrysin. The yield of Chrysin is
around 0.25 g. Further elution of the column with 3% methanol in
chloroform afforded Baicalein. The yield of Baicalein is around 1.5
g. Further elution of the column successively with 4% methonal in
chloroform afford Methoxy chrysin. The yield of methoxy chrysin is
around 0.5 g. Further elution of the column with 5% methonal in
chloroform afford Oroxyloside methyl ester. The yield of
Oroxyloside methyl ester is around 0.4 g. Further evolution of the
column with 7% methanol in chloroform afford chrysin-7-O-methyl
gluconide. The yield of the chrysin-7-O-methyl gluconide is around
0.3 g. All the above compounds were isolated in 95% purity.
[0078] The spectrochemical and physical properties of the all the
above compounds are discussed earlier. Further all the synthetic
analogues preparation and yields were discussed in earlier
procedures.
EXAMPLE 2
Experimental Method for Gastric Ulcer
[0079] The compounds taken under study for antigastric ulcer
screening by four different models were selected using experimental
albino rats: [0080] 1. Aspirin induced gastric ulceration [0081] 2.
Pylorus ligated gastric ulceration [0082] 3. Ethanol induced
gastric ulceration [0083] 4. Stress induced gastric ulceration
[0084] The commercially available drug ranitidine (sigma),
Omeprazole (sigma) and sucralfate (Merck) were used as reference
standard in experimental models. The Tween-80 (SD fine chemicals)
was used as vehicle for the administration of the drug, which is
used as control. The results obtained are presented in the
following tables.
2.1 Acetyl Salicylic Acid Induced Ulcer:
[0085] Antiulcer activity of the compounds under taken was studied.
The animals were divided into 20 groups of 6 animals each. Group 1
received the vehicle Tween 80 (1%, 1 ml) which served as the
control. Group 2 received ranitidine at a dose of 50-mg/kg body
weight, which served as standard for comparison. Group 3 to 20 at a
dose of 25 mg/kg body weight. Rats were administered per orally
with a daily dose of the compounds and the drug ranitidine for a
period of five days and then fasted for 24 hours. The narcotizing
agent acetyl salicylic acid (aspirin) at a dose of 200 mg/kg body
weight was administered as a suspension in tween-80 (1%), 30 min
after the drug administration each day. All drugs were administered
orally on the 6th day after the last administration of the drugs
and the ulcer inducing agent aspirin, the rats were killed by
cervical dislocation and their stomach were opened along the
greater curvature and washed with luke warm saline and examined
under a dissecting microscope. The ulcer index was calculated for
each stomach. The results are given in table no. 1.
2.2 Cold Restraint Induced Ulcers
[0086] The antiulcer activity of the compounds was studied. The
animals were divided into 21 groups of 7 animals each. Group 1
received the vehicle Tween 80 (1%, 1 ml) which served as the
control. Group 2 received ranitidine at a dose of 50-mg/kg body
weight, which served as standard for comparison. Group 3 to 21 at a
dose of 25 mg/kg body weight. Animals were deprived of food 48
hours before the experiment. The water was allowed for free access.
Rats were administered per orally with compounds and the drug
ranitidine. The water was removed 1 hour before restraint and
exposed to a temperature of 4.degree. C. for 2 hours. Two hours
after stress, the animals were sacrificed. The stressed animals
were opened along the greater curvature and the severity of gastric
ulcer was assessed in terms of mean ulcer index. Results are
tabulated below in table no. 2.
2.3 Ethanol Induced Ulcers
[0087] The animals were divided into 22 groups of 6 animals each.
Animals were deprived of food for 48 hours but had free access to
water. Group 1 received the vehicle Tween 80 (1%, 1 ml) which
served as the control. Group 2 received ranitidine at a dose of
50-mg/kg-body weight, which served as standard for comparison.
Group 3 to received Omeprazole at a dose of 30-mg/kg body weight,
which served as standard for comparison. Group 4 received
sucralfate at a dose of 400-mg/kg body weight, which served as
standard for comparison. Group 5 to 22 received at a dose of 25
mg/kg body weight. Lesions were induced 1 hour after ethanol
challenge animals. The stomach was ligated at the pylorus under
ether anesthesia. 4 hours after pylorus ligation, the animals were
sacrificed and the contents drained and centrifuges at 5000 rpm for
10 minutes. Aliquots of supernatant were used for determination of
total acid by titrating with 0.01N NaOH using topfers reagent and
phenolphthalein indicators. Results are tabulated in Table no.
3.
2.4 Pylorus Ligated Ulcers
[0088] The animals were divided into 19 groups of 6 animals each.
Animals were deprived of food for 48 hours but had free access to
water. Group 1 received the vehicle Tween 80 (1%, 1 ml) which
served as the control. Group 2 received ranitidine at a dose of
50-mg/kg-body weight, which served as standard for comparison.
Group 3 to 20 received at a dose of 25 mg/kg body weight. After one
hour of administration of drug the stomach was ligated at the
pylorus under ether anesthesia. 4 hours after pylorus ligation, the
animals were sacrificed and the contents drained and centrifuges at
5000 rpm for 10 minutes. Aliquots of supernatant were used for
determination of total acid by titrating with 0.01N NaOH using
topfers reagent and phenolphthalein indicators. Results are given
in table no. 4.
2.5 Acetyl Salicylic Acid Induced Ulcer:
[0089] The antiulcer activity of the compounds was studied. The
animals were divided into 19 groups of 6 animals each. Group 1
received the vehicle Tween 80 (1%, 1 ml) which served as the
control. Group 2 received ranitidine at a dose of 50-mg/kg-body
weight, which served as standard for comparison. Group 3 to 8 at a
dose of 50, 25, 15, 10 and 5 mg/kg body weight respectively. Rats
were administered per orally with a daily dose of the compounds and
the drug ranitidine to respective groups for a period of five days
and then fasted for 24 hours. The narcotizing agent acetyl
salicylic acid (aspirin) at a dose of 200 mg/kg body weight was
administered as a suspension in tween-80 (1%), 30 min after the
drug administration each day. All drugs were administered orally on
the 6th day after the last administration of the drugs and the
ulcer inducing agent aspirin, the rats were killed by cervical
dislocation and their stomach were opened along the greater
curvature and washed with luke warm saline and examined under a
dissecting microscope. The ulcer index was calculated for each
stomach and is given in Table 5.
2.6 Cold Restraint Induced Ulcers
[0090] The antiulcer activity of the compounds was studied. The
animals were divided into 8 groups of 6 animals each. Group 1
received the vehicle Tween 80 (1%, 1 ml) which served as the
control. Group 2 received ranitidine at a dose of 50-mg/kg body
weight, which served as standard for comparison. Group 3 to 8 at a
dose of 50, 25, 15, 10 and 5 mg/kg body weight respectively.
Animals were deprived of food 48 hours before the experiment. The
water was allowed for free access. Rats were administered per
orally with compounds and the drug ranitidine. The water was
removed 1 hour before restraint and exposed to a temperature of
4.degree. C. for 2 hours. Two hours after stress, the animals were
sacrificed. The stressed animals were opened along the greater
curvature and the severity of gastric ulcer was assessed in terms
of mean ulcer index. Results are given in Table 6.
2.7 Ethanol Induced Ulcers
[0091] The animals were divided into 9 groups of 6 animals each.
Animals were deprived of food for 48 hours but had free access to
water. Group 1 received the vehicle Tween 80 (1%, 1 ml) which
served as the control. Group 2 received ranitidine at a dose of
50-mg/kg-body weight, which served as standard for comparison.
Group 3 to received Omeprazole at a dose of 30-mg/kg body weight,
which served as standard for comparison. Group 4 received
sucralfate at a dose of 400-mg/kg body weight, which served as
standard for comparison. Group 5 to 9 received at a dose of 50, 25,
15, 10 and 5 mg/kg body weight respectively. Lesions were induced 1
hour after ethanol challenge animals. The stomach was ligated at
the pylorus under ether anesthesia. 4 hours after pylorus ligation,
the animals were sacrificed and the contents drained and
centrifuges at 5000 rpm for 10 minutes. Aliquots of supernatant
were used for determination of total acid by titrating with 0.01N
NaOH using topfers reagent and phenolphthalein indicators. Results
are given in Table 7.
2.8 Pylorus Ligated Ulcers
[0092] The animals were divided into 7 groups of 6 animals each.
Animals were deprived of food for 48 hours but had free access to
water. Group 1 received the vehicle Tween 80 (1%, 1 ml) which
served as the control. Group 2 received ranitidine at a dose of
50-mg/kg-body weight, which served as standard for comparison.
Group 3 to 7 received at a dose of 50, 25, 15, 10 and 5 mg/kg body
weight respectively. After one hour of administration of drug the
stomach was ligated at the pylorus under ether anesthesia. 4 hours
after pylorus ligation, the animals were sacrificed and the
contents drained and centrifuges at 5000 rpm for 10 minutes.
Aliquots of supernatant were used for determination of total acid
by titrating with 0.01N NaOH using topfers reagent and
phenolphthalein indicators. Results are given in Table 8.
TABLE-US-00001 TABLE 1 Ulcer protective effect of samples in acetyl
salicylic acid induced gastric lesions Ulcer Inhi- Group No. of
Average Dose index bition no. animals weight Treatment (mg/kg)
Mean(SE) % 1 6 180 Control 1 ml 45.12 (.+-.1.82) -- (1%) 2 6 180
Ranitidine 50 11.66 (.+-.3.00) 74.15 3 6 180 OA-5 25 11.06
(.+-.2.10) 74.55 4 6 180 Oroxylin 25 42.50 (.+-.1.70) 05.81 A 5 6
182 Chrysin 25 24.06 (.+-.0.24) 46.67 6 6 180 Baicalein 25 40.83
(.+-.3.09) 09.51 7 6 180 Methoxy 25 40.00 (.+-.2.88) 11.35 chrysin
8 6 181 ORC-16 25 39.13 (.+-.3.74) 13.27 9 6 182 ORPM-1 25 37.49
(.+-.3.27) 16.91 10 6 180 NMC-2 25 23.33 (.+-.6.00) 48.30 11 6 181
NMC-3 25 30.00 (.+-.5.62) 33.52 12 6 180 CHN-2 25 20.00 (.+-.4.21)
55.68 13 6 182 CHM-2 25 19.99 (.+-.6.66) 55.59 14 6 181 CHM-3 25
21.77 (.+-.3.65) 51.74 15 6 179 CPP-2 25 14.99 (.+-.3.07) 66.77 16
6 180 OA-G 25 30.66 (.+-.1.76) 32.05 17 6 180 OA-5 acid 25 23.33
(.+-.8.81) 48.30 18 6 180 CG 25 21.66 (.+-.3.33) 52.00 19 6 181 CGL
25 13.33 (.+-.1.66) 70.46 OA-5 = Oroxyloside methyl ester (FIG.: 5)
Oroxylin A = (FIG.: 1) Chrysin = (FIG.: 2) Baicalein = (FIG.: 3)
Methoxy chrysin = (FIG: 4) ORC-16 = (FIG.: 7) ORPM-1 = (FIG.: 8)
NMC-2 = (FIG.: 12) NMC-3 = (FIG.: 13) CHN-2 = (FIG.: 11) CHM-2 =
(FIG.: 10) CHM-3 = (FIG.: 14) CPP-2 = (FIG.: 9) OA-G = (FIG.: 15)
OA-5 acid = (FIG.: 17) CG = (FIG.: 16) CGL = (FIG.: 6)
TABLE-US-00002 TABLE 2 Effect of samples on gastric ulceration in
cold restraint rats Ulcer Inhi- Group No. of Average Dose index
bition no. animals weight Treatment (mg/kg) Mean (SE) % 1 7 170
Control 1 ml 40.17 (.+-.3.99) -- (1%) 2 7 170 Ranitidine 50 08.62
(.+-.2.85) 78.83 3 7 170 Diazepam 1 10.00 (.+-.2.18) 75.44 4 7 170
OA-5 25 9.997 (.+-.1.84) 75.45 5 7 171 Oroxylin 25 38.57 (.+-.4.04)
5.26 A 6 7 172 Chrysin 25 23.03 (.+-.0.25) 42.66 7 7 170 Baicalein
25 29.28 (.+-.2.52) 3.52 8 7 172 Methoxy 25 27.14 (.+-.2.85) 8.77
chrysin 9 7 170 ORC-16 25 35.00 (.+-.2.43) 14.03 10 7 171 ORPM-1 25
22.85 (.+-.2.85) 24.23 11 7 170 NMC-2 25 16.42 (.+-.2.76) 59.67 12
7 170 NMC-3 25 17.13 (.+-.3.40) 57.92 13 7 171 CHN-2 25 17.85
(.+-.2.97) 56.12 14 7 171 CHM-2 25 26.42 (.+-.0.92) 35.11 15 7 170
CHM-3 25 19.28 (.+-.4.08) 52.64 16 7 170 CPP-2 25 15.71 (.+-.2.60)
61.44 17 7 171 OA-G 25 32.33 (.+-.1.45) 19.52 18 7 172 OA-5 acid 25
23.33 (.+-.1.33) 41.93 19 7 170 CG 25 21.00 (.+-.2.00) 47.73 20 7
170 CGL 25 20.00 (.+-.1.73) 50.22
TABLE-US-00003 TABLE 3 Ulcer protective effect of samples on
ethanol induced gastric ulcers Group No. of Average Dose Gastric
Acidity Ulcer index Inhibition no. animals weight Treatment (mg/kg)
content pH Total m Eg Mean(SE) % 1 6 190 Control 1 ml (1%) 3.9
(.+-.0.02) 2.66 (.+-.0.22) 62.00 (.+-.2.71) 66.66 (.+-.1.66) -- 2 6
190 Ranitidine 50 5.0 (.+-.0.48) 4.96 (.+-.0.13) 26.74 (.+-.1.54)
25.83 (.+-.2.22) 61.26 3 6 190 Omeprazole 30 3.5 (.+-.0.68) 4.65
(.+-.0.19) 32.01 (.+-.1.52) 23.33 (.+-.2.21) 67.51 4 6 190
Sucralfate 400 3.01 (.+-.0.48) 3.00 (.+-.0.19) 58.00 (.+-.2.30)
08.33 (.+-.2.23) 87.50 5 6 190 OA-5 25 5.5 (.+-.0.30) 6.81
(.+-.0.26) 12.40 (.+-.2.30) 11.66 (.+-.4.47) 82.50 6 6 191 Oroxylin
A 25 4.0 (.+-.0.45) 3.19 (.+-.0.73) 48.24 (.+-.2.84) 48.33
(.+-.3.33) 27.50 7 6 190 Chrysin 25 4.20 (.+-.0.02) 3.20 (.+-.0.40)
48.00 (.+-.2.20) 60.66 (.+-.2.88) 09.01 8 6 191 Baicalein 25 3.5
(.+-.0.20) 3.33 (.+-.0.10) 45.21 (.+-.3.10) 43.33 (.+-.3.33) 20.00
9 6 192 Methoxy 25 3.9 (.+-.0.40) 2.91 (.+-.0.15) 49.20 (.+-.4.12)
46.66 (.+-.1.66) 15.01 chrysin 10 6 191 ORC-16 25 3.7 (.+-.0.10)
3.58 (.+-.0.23) 43.20 (.+-.3.86) 51.50 (.+-.1.05) 22.75 11 6 192
ORPM-1 25 3.0 (.+-.1.50) 3.50 (.+-.0.18) 44.24 (.+-.0.62) 47.50
(.+-.1.11) 28.75 12 6 190 NMC-2 25 4.8 (.+-.0.06) 4.75 (.+-.0.28)
30.26 (.+-.0.42) 28.33 (.+-.3.33) 57.50 13 6 189 NMC-3 25 4.5
(.+-.1.12) 4.50 (.+-.0.18) 33.48 (.+-.2.28) 42.50 (.+-.3.09) 36.25
14 6 190 CHN-2 25 3.2 (.+-.0.42) 5.14 (.+-.0.36) 28.10 (.+-.0.48)
38.33 (.+-.3.07) 42.50 15 6 190 CHM-2 25 2.8 (.+-.0.72) 4.00
(.+-.0.18) 38.28 (.+-.2.24) 40.11 (.+-.3.65) 25.00 16 6 190 CHM-3
25 3.8 (.+-.0.30) 4.16 (.+-.0.12) 37.10 (.+-.0.60) 42.50 (.+-.3.81)
36.25 17 6 190 CPP-2 25 3.2 (.+-.0.62) 3.33 (.+-.0.16) 44.60
(.+-.4.12) 28.83 (.+-.2.71) 36.25 18 6 190 OH-mix 25 2.6 (.+-.0.25)
4.33 (.+-.0.10) 35.20 (.+-.3.86) 35.10 (.+-.5.41) 32.50 19 6 190
OA-G 25 4.33 (.+-.0.11) 4.31 (.+-.0.11) 36.66 (.+-.0.88) 53.33
(.+-.6.66) 20.00 20 6 192 OA-5 acid 25 5.50 (.+-.0.28) 3.20
(.+-.0.17) 47.66 (.+-.1.45) 36.66 (.+-.3.33) 45.01 20 6 189 CG 25
5.90 (.+-.0.49) 5.90 (.+-.0.49) 20.01 (.+-.4.41) 31.66 (.+-.4.41)
52.50 21 6 189 CGL 25 4.60 (.+-.0.20) 3.91 (.+-.0.21) 39.00
(.+-.1.52) 25.00 (.+-.2.88) 62.50
TABLE-US-00004 TABLE 4 Antisecretory and ulcer protective effect of
samples in Pylorus ligated rats Average Group No. of weight Dose
Gastric Acidity Ulcer index Inhibition no. animals (g) Treatment
(mg/kg) content pH Total mEg Mean(SE) % 1 6 195 Control 1% 2.24
(.+-.0.22) 2.83 (.+-.0.33) 52.42 (.+-.3.28) 50.11 (.+-.3.65) -- 2 6
195 Ranitidine 50 1.82 (.+-.0.44) 4.75 (.+-.0.22) 31.8 (.+-.1.91)
10.83 (.+-.3.21) 78.39 3 6 196 OA-5 25 2.10 (.+-.0.34) 5.62
(.+-.0.19) 30.18 (.+-.0.50) 12.49 (.+-.3.74) 75.07 4 6 196 Oroxylin
A 25 2.30 (.+-.0.42) 2.74 (.+-.0.24) 55.24 (.+-.2.40) 50.80
(.+-.2.00) 0.00 5 6 192 Chrysin 25 1.85 (.+-.0.82) 4.00 (.+-.0.40)
56.00 (.+-.0.82) 37.21 (.+-.0.26) 25.74 6 6 195 Baicalein 25 2.00
(.+-.0.22) 3.01 (.+-.0.30) 49.21 (.+-.2.20) 40.66 (.+-.5.50) 18.86
6 195 Methoxy 25 2.20 (.+-.0.44) 3.20 (.+-.0.25) 47.20 (.+-.2.40)
48.80 (.+-.3.07) 2.62 chrysin 7 6 194 ORC-16 25 1.92 (.+-.0.20)
3.66 (.+-.0.20) 42.20 (.+-.2.20) 43.33 (.+-.2.10) 1354 8 6 195
ORPM-1 25 2.20 (.+-.0.22) 3.20 (.+-.0.25) 45.24 (.+-.0.30) 41.66
(.+-.2.78) 16.87 9 6 195 NMC-2 25 1.90 (.+-.0.62) 4.25 (.+-.0.14)
36.26 (.+-.2.80) 28.33 (.+-.0.10) 43.47 10 6 195 NMC-3 25 1.92
(.+-.0.20) 3.54 (.+-.0.15) 43.48 (.+-.2.50) 33.33 (.+-.2.47) 33.49
11 6 194 CHN-2 25 1.80 (.+-.0.46) 4.25 (.+-.0.09) 37.18 (.+-.4.20)
20.83 (.+-.2.00) 58.44 12 6 195 CHM-2 25 1.88 (.+-.0.62) 3.79
(.+-.0.20) 41.48 (.+-.3.20) 25.82 (.+-.2.00) 48.47 13 6 196 CHM-3
25 2.24 (.+-.0.22) 3.41 (.+-.0.16) 44.10 (.+-.2.20) 27.46
(.+-.3.00) 45.19 14 6 195 CPP-2 25 2.60 (.+-.0.24) 3.25 (.+-.0.11)
29.06 (.+-.2.20) 15.80 (.+-.2.71) 68.47 15 6 194 OH-mix 25 2.40
(.+-.0.24) 3.87 (.+-.0.19) 40.20 (.+-.2.10) 32.50 (.+-.1.11) 35.15
16 6 196 OA-G 25 4..50 (.+-.0.28) 3.20 (.+-.0.15) 41.66 (.+-.1.66)
35.00 (.+-.2.88) 30.16 17 6 195 OA-5 acid 25 2.16 (.+-.0.16) 3.03
(.+-.0.03) 41.00 (.+-.0.57) 38.33 (.+-.1.66) 23.51 18 6 195 CG 25
1.50 (.+-.0.28) 3.50 (.+-.0.28) 44.33 (.+-.2.33) 24.93 (.+-.1.66)
50.25 19 6 194 CGL 25 4.83 (.+-.0.44) 3.08 (.+-.0.22) 40.00
(.+-.1.15) 19.96 (.+-.6.66) 60.17 20 6 192 Chrysin 25 1.85
(.+-.0.82) 4.00 (.+-.0.40) 56.00 (.+-.0.82) 37.21 (.+-.0.26)
25.74
TABLE-US-00005 TABLE 5 Ulcer protective effect of OA - 5 in acetyl
salicylic acid induced gastric lesions Ulcer Inhi- Group No. of
Average Dose index bition no. animals weight Treatment (mg/kg)
Mean(SE) % 1 6 180 Control 1 ml 45.12 (.+-.1.82) -- (1%) 2 6 180
Ranitidine 50 11.66 (.+-.3.00) 74.15 3 6 180 OA-5 50 10.00
(.+-.3.50) 77.84 4 6 180 OA-5 25 11.06 (.+-.2.10) 74.55 5 6 180
OA-5 15 26.66 (.+-.7.20) 40.98 6 6 180 OA-5 10 26.66 (.+-.4.70)
40.98 7 6 181 OA-5 5 36.66 (.+-.2.72) 18.75
TABLE-US-00006 TABLE 6 Effect of OA - 5 on gastric ulceration in
cold restraint rats Ulcer Inhi- Group No. of Average Dose index
bition no. animals weight Treatment (mg/kg) Mean(SE) % 1 6 170
Control 1 ml 40.17 (.+-.3.99) -- (1%) 2 6 170 Ranitidine 50 08.62
(.+-.2.85) 78.83 3 6 170 Diazepam 1 10.00 (.+-.2.18) 75.44 4 6 170
OA-5 50 8.75 (.+-.2.16) 78.22 5 6 170 OA-5 25 9.99 (.+-.1.84) 75.45
6 6 170 OA-5 15 19.99 (.+-.5.4) 50.14 7 6 172 OA-5 10 23.33
(.+-.4.74) 41.92 8 6 171 OA-5 5 27.5 (.+-.4.14) 31.55
TABLE-US-00007 TABLE 7 Ulcer protective effect of OA - 5 on ethanol
induced gastric ulcers Group No. of Average Dose Gastric Acidity
Ulcer index Inhibition no. animals weight Treatment (mg/kg) content
pH Total m Eg Mean(SE) % 1 6 190 Control 1 ml (1%) 3.9 (.+-.0.02)
2.66 (.+-.0.22) 62.00 (.+-.2.71) 66.66 (.+-.1.66) -- 2 6 190
Ranitidine 50 5.0 (.+-.0.48) 4.96 (.+-.0.13) 26.74 (.+-.1.54) 25.83
(.+-.2.22) 61.26 3 6 190 Omeprazole 30 3.5 (.+-.0.68) 4.65
(.+-.0.19) 26.01 (.+-.1.52) 23.33 (.+-.2.21) 67.51 4 6 190
Sucralfate 400 3.0 (.+-.0.48) 3.00 (.+-.0.19) 58.00 (.+-.2.30)
08.33 (.+-.2.23) 87.50 5 6 190 OA-5 50 7.4 (.+-.0.72) 4.95
(.+-.0.43) 18.25 (.+-.7.10) 10.00 (.+-.6.23) 85.00 6 6 191 OA-5 25
5.5 (.+-.0.30) 6.81 (.+-.0.26) 12.40 (.+-.2.30) 11.66 (.+-.4.47)
82.50 7 6 192 OA-5 15 4.0 (.+-.0.82) 4.5 (.+-.0.13) 29.66
(.+-.1.36) 26.66 (.+-.4.71) 60.61 8 6 191 OA-5 10 4.2 (.+-.0.07)
4.66 .+-. (0.13) 31.33 (.+-.1.36) 43.33 (.+-.5.40) 35.00 9 6 191
OA-5 5 4.0 (.+-.0.45) 3.5 (.+-.0.40) 42.66 (.+-.3.95) 46.66
(.+-.0.80) 30.01
TABLE-US-00008 TABLE 8 Antisecretory and ulcer protective effect of
OA - 5 in Pylorus ligated rats Average Group No. of weight Dose
Gastric Acidity Ulcer index Inhibition no. animals (g) Treatment
(mg/kg) content pH Total mEg Mean(SE) % 1 6 190 Control 1% 2.24
(.+-.0.22) 2.83 (.+-.0.33) 52.42 (.+-.3.28) 50.11 (.+-.3.65) -- 2 6
190 Ranitidine 50 1.82 (.+-.0.44) 4.75 (.+-.0.22) 31.8 (.+-.1.91)
10.83 (.+-.3.21) 78.39 3 6 190 OA-5 50 2.50 (.+-.0.19) 4.62
(.+-.0.10) 32.66 (.+-.0.62) 10.10 (.+-.2.04) 79.85 4 6 191 OA-5 25
2.10 (.+-.0.34) 5.62 (.+-.0.19) 30.18 (.+-.0.50) 12.49 (.+-.3.74)
75.07 5 6 192 OA-5 15 3.62 (.+-.0.61) 4.35 (.+-.0.10) 30.25
(.+-.0.73) 15.00 (.+-.3.33) 70.07 6 6 190 OA-5 10 3.50 (.+-.0.62)
3.58 (.+-.0.24) 42.90 (.+-.2.37) 21.66 (.+-.3.04) 59.78 7 6 189
OA-5 5 2.06 (.+-.0.28) 3.25 (.+-.0.17) 45.50 (.+-.1.25) 26.66
(.+-.5.48) 46.80
* * * * *