JP2005526791A - Composition for treating gastric ulcer and method for producing the same - Google Patents

Abstract

The present invention relates to a novel synergistic herb composition for the treatment of gastric ulcer, a method for producing the synergistic herb composition, and a method for treating gastric ulcer using the composition. More specifically, the present invention relates to pyloric ligation. The present invention relates to a novel synergistic herb composition effective against an induced ulcer model and a histamine-induced ulcer model.

Description

  The present invention relates to a novel synergistic herbal composition for the treatment of gastric ulcers. More specifically, the present invention relates to a novel synergistic herb composition effective against a pyloric ligation-induced ulcer model and a histamine-induced ulcer model. The invention also relates to a method for producing the composition. The present invention further relates to a method for treating gastric ulcer using the composition.

  Various theories have been proposed as the cause of ulcers in humans. In particular, it has been clarified that administration of non-steroidal anti-inflammatory drugs to cure stress, rheumatic diseases, etc. is closely related to ulceration, mainly due to relatively excessive gastric or duodenal acid secretion . Therefore, in order to prevent and cure ulcer formation, it is important to suppress acid secretion.

  On the other hand, Helicobactor pylori, a gonococcal resident in the stomach, was thought to induce ulcers by generating ammonia due to its strong urease activity. It is the greatest cause of ulcer recurrence because it survives permanently in mucus and mucous membranes. Therefore, it was thought that if this bacterium was killed, recurrence of the ulcer could be prevented.

  Regarding the medicinal properties of Blechnum orintale, KMNadkarni, Indian Materia Medica (1976) Vol.1, p.1287, Popular Prakashan Pvt. Ltd., Mumbai and KRKirtikar, Indian Medicinal Plants (1975) Vol.1, p.608 For reference, Dehradun, published by Bishen Singh Mahendrapal Singh.

  Regarding the various medicinal effects of Vitis vinifera, PK Warrier, Indian Medicinal Plants-A compendium of 500 species (1994-1996) Vol. 5, p. 396 and The wealth of India (1950-1980), Vol. 10, p. 556, Council of Scientific and Industrial Research published for reference.

  Regarding the various medicinal properties of Aegle marmelos, K. Narayana Iyer and M. Kolammal, Pharmacognosy of Ayurvedic Drugs (1963) Vol. 2, p. 80, Department of Pharmacognosy, University of Kerala, Trivandrum and The Wealth of India (1950 -1980) Vol.1, p.34, published by Council of Scientific and Industrial Research.

  Regarding the various medicinal properties of Withania somnifra, KMNadkarni, Indian Materia Medica (1976) Vol.1, p.1239-94, Popular Prakashan Pvt. Ltd., Mumbai; KRKirtikar, Indian Medicinal Plants (1975) Vol.2 , p. 1776, published by Bishen Singh Mahendrapal Singh, Dehradun; PK Warrier, Indian Medicinal Plants-A compendium of 500 species (1994-1996) Vol. 5, p. 409; K. Narayana Iyer and M. Kolammal, Pharmacognosy of Ayurvedic Drugs (1963) Vol. 8, p. 34, published by Department of Pharmacognosy, University of Kerala, Trivandrum; The Wealth of India (1950-1980) Vol. 10, p. 585, published by Council of Scientific and Industrial Research; and SS Handa, Indian Herbal Pharmacopoeia (1998) Vol.1, p.171, published by Regional Research Laboratory, Jammu and IDMA, Mumbai.

  Regarding the various medicinal properties of Feronia elephantum, KMNadkarni, Indian Materia Medica (1976) Vol.1, p.536, Popular Prakashan Pvt. Ltd., Mumbai; KRKirtikar, Indian Medicinal Plants (1975) Vol.1, p. 997, published by Bishen Singh Mahendrapal Singh, Dehradun; PK Warrier, Indian Medicinal Plants-A compendium of 500 species (1994-1996) Vol. 3, p. 327-29; and The Wealth of India (1950-1980) Vol. 4, p.19, published by Council of Scientific and Industrial Research.

  Regarding the various medicinal properties of Punica grantum, KMNadkarni, Indian Materia Medica (1976) Vol.1, p.1031, Popular Prakashan Pvt. Ltd., Mumbai; PKWarrier, Indian Medicinal Plants-A compendium of 500 species (1994 -1996) Vol.4, p.396; and Illustrated manual of herbal drugs used in Ayurveda (1996) YKSarin, p.218.

  Regarding various pharmacological effects of Ziniber officnale, KMNadkarni, Indian Materia Medica (1976) Vol.1, p.1031, Popular Prakashan Pvt. Ltd., Mumbai; KRKirtikar, Indian Medicinal Plants (1975) Vol.4, p. 2436, published by Bishen Singh Mahendrapal Singh, Dehradun; PK Warrier, Indian Medicinal Plants-A compendium of 500 species (1994-1996) Vol. 5, p. 431, published by Orient Longman, Chennai; and The Ayurvedic Pharmacopoeia of India (1986 ) Vol.1, p.104. Published by Ministry of Health and Family Welfare, India is helpful.

  Regarding the various medicinal effects of Piper nigrum, KMNadkarni, Indian Materia Medica (1976) Vol.1, p.478, Popular Prakashan Pvt. Ltd., Mumbai; PKWarrier, Indian Medicinal Plants-A compendium of 500 species (1994 -1996) Vol.2, p.368, published by Orient Longman, Chennai; Medicinal plants of India (1987), GVSatyavati, Vol.2, p.429, published by Indian Council of Medical Research; The Wealth of India (1950- 1980) Vol. 8, p. 98, published by Council of Scientific and Industrial Research; and YKSarin, Illustrated manual of herbal drugs used in Ayurveda (1996) p. 268.

  Regarding the various medicinal properties of Piper longum, KMNadkarni, Indian Materia Medica (1976) Vol.1, p.966, Popular Prakashan Pvt. Ltd., Mumbai; PKWarrier, Indian Medicinal Plants-A compendium of 500 species (1994 -1996) Vol.4, p.290, published by Orient Longman, Chennai; K. Narayana Iyer and M. Kolammal, Pharmacognosy of Ayurvedic Drugs (1963) Vol.9, p.49, Department of Pharmacognosy, University of Kerala, Trivandrum; and The Wealth of India (1950-1980) Vol. 8, p. 98, published by Council of Scientific and Industrial Research.

  Regarding the various medicinal properties of Azadirachta indica, KRKirtikar, Indian Medicinal Plants (1975) Vol.1, p.536-540, published by Bishen Singh Mahendrapal Singh, Dehradun; PKWarrier, Indian Medicinal Plants-A compendium of 500 species -1996) Vol.1, p.203-5, published by Orient Longman; and K. Narayana Iyer and M. Kolammal, Pharmacognosy of Ayurvedic Drugs (1963) Vol.3, p.23, issued by Department of Pharmacognosy, University of Kerala , Trivandrum is helpful.

  The composition of the present invention should not be treated as obvious, since none of the cited examples is capable of exerting all the advantages of the present invention.

Object of the invention

  The main object of the present invention is to provide a novel synergistic herbal composition for the treatment of gastric ulcers. Another object of the present invention is to provide a method for producing the composition. Still another object of the present invention is to provide a method for treating gastric ulcer using the composition.

Summary of the Invention

  The present invention provides a novel synergistic herbal composition for the treatment of gastric ulcers. More specifically, the present invention relates to a novel synergistic herb composition effective against a pyloric ligation-induced ulcer model and a histamine-induced ulcer model. Moreover, the present invention provides a method for producing the composition. The present invention further provides a method for treating gastric ulcer using the composition.

Detailed Description of the Invention

  According to a first object of the present invention, a novel synergistic herbal composition for the treatment of gastric ulcer is provided, said composition essentially from one or more sites of Aegle marmelos and Withania somnifra and optionally Blechnum. Extracts from one or more sites of orintale, Vitis vinifera, Feronia elephantum, Punica grantum, Ziniber officnale, Piper nigrum, Piper longum and Azadirachta indica together with one or more pharmaceutically acceptable additives / carriers Contains.

  More particularly, the present invention provides a novel synergistic herb composition for the treatment of gastric ulcers, which consists essentially of 4-10% by weight of an extract of Aegle marmelos and 4-11% by weight of an extract of Withania somnifra. 5-8% by weight of Blechnum orintale extract, 5-11% by weight of Vitis vinifera, 5-9% by weight of Feronia elephantum extract, 8-11% by weight of Punica grantum extract One or more of Ziniber officnale extract 4-9 wt%, Piper nigrum extract 2-11 wt%, Piper longum extract 8-12 wt% and Azadirachta indica extract 2-11 wt% Contains along with pharmaceutically acceptable additives / carriers.

  In an embodiment of the invention, the extract is an aqueous extract. In another embodiment of the invention, the plant part of Aegle marmelos, Withania somnifra and Blechnum orintale is a root. In yet another embodiment of the invention, the plant parts of Vitis vinifera, Feronia elephantum, Piper nigrum and Piper longum are fruits. In yet another embodiment of the present invention, the plant part of Punica grantum is fruit skin. In another embodiment of the invention, the plant part of Ziniber officnale is a rhizome. In another embodiment of the invention, the plant part of Azadirachta indica is bark.

  According to a second object of the present invention, there is provided a process for the preparation of a novel synergistic herb composition for the treatment of gastric ulcers, said process essentially from one or more sites of Aegle marmelos and Withania somnifra and To obtain extracts from one or more sites of Blechnum orintale, Vitis vinifera, Feronia elephantum, Punica grantum, Ziniber officnale, Piper nigrum, Piper longum and Azadirachta indica, which are one or more pharmaceutically acceptable additives / carriers And mixed with.

  In an embodiment of the invention, the extract of the above method comprises 4-10% by weight of an extract of Aegle marmelos and 4-11% by weight of an extract of Withania somnifra, optionally 5-8% by weight of an extract of Blechnum orintale, Vitis vinifera 5-11 wt% extract, Feronia elephantum extract 5-9 wt%, Punica grantum extract 8-11 wt%, Ziniber officnale extract 4-9 wt%, Piper nigrum extract 2-11 Crushing by weight, 8-12% by weight of Piper longum extract and 2-11% by weight of Azadirachta indica extract into fine pastes and mixing them with one or more pharmaceutically acceptable additives / carriers Is obtained.

  In another embodiment of the invention, the extract is an aqueous extract. In yet another embodiment of the present invention, the plant part of Aegle marmelos, Withania somnifra and Blechnum orintale is a root. In yet another embodiment of the invention, the plant parts of Vitis vinifera, Feronia elephantum, Piper nigrum and Piper longum are fruits. In another embodiment of the present invention, the plant part of Punica grantum is fruit skin. In another embodiment of the invention, the plant part of Ziniber officnale is a rhizome. In an embodiment of the invention, the plant part of Azadirachta indica is bark.

  According to a third object of the present invention, there is provided a method for treating gastric ulcer in a subject comprising essentially 4-10% by weight of an extract of Aegle marmelos and 4-11% by weight of an extract of Withania somnifra. 5 to 8% by weight of Blechnum orintale extract, 5 to 11% by weight of extract of Vitis vinifera, 5 to 9% by weight of extract of Feronia elephantum, 8 to 11% by weight of extract of Punica grantum, One or more pharmaceuticals containing 4-9% by weight of Ziniber officnale extract, 2-11% by weight of Piper nigrum extract, 8-12% by weight of Piper longum extract and 2-11% by weight of Azadirachta indica extract It consists of administering an effective amount of the synergistic herb composition contained together with an acceptable additive / carrier.

  In an embodiment of the present invention, the subject is a mammal including a human. In another embodiment of the invention, 50-100 mg of composition is administered to a subject per kg body weight. In yet other embodiments of the invention, the composition takes the form of a tablet, capsule, syrup or any other form known in the art. In yet another embodiment of the invention, the composition is administered orally, intramuscularly and any other conventional manner. In another embodiment of the invention, the composition is used for therapeutic and prophylactic treatment of gastric ulcers. In another embodiment of the invention, the subject is administered in a single bolus dose or multiple doses.

Brief description of the table <br/> In the table attached to the description ,
Table 1 shows the effect of Omeprazole (standard drug) and novel herbal composition (HF) on the Cold Restraint Ulcer (CRU) model.
Table 2 compares the protective rate of Omeprazole and herbal composition (HF) against the cold-restrained ulcer (CRU) model.
Table 3 represents the effect of Omeprazole and herbal composition (HF) on the aspirin-induced ulcer model.
Table 4 represents the protection rate of Omeprazole and herbal composition (HF) against the aspirin-induced ulcer model.
Table 5 shows the effect of Omeprazole and herbal composition (HF) on histamine-induced duodenal ulcers in guinea pigs.

Table 6 represents the protection rate of Omeprazole and herbal composition (HF) against histamine-induced duodenal ulcers in guinea pigs.
Table 7 represents the effect of Omeprazole and herbal composition (HF) on the ethanol-induced ulcer model.
Table 8 represents the protection rate of Omeprazole and herbal composition (HF) against the alcohol-induced ulcer model.
Table 9 represents the effect of Omeprazole and herbal composition (HF) on pyloric ligation-induced ulcers.
Table 10 represents the protection rate of Omeprazole and herbal composition (HF) against pyloric ligation-induced ulcers.
Table 11 represents the composition of the herbal composition (HF) of the present invention.

  The present invention will be further described with reference to the following experiments, which are given for the purpose of illustration and therefore should in no way be construed as limiting the scope of the invention.

Experimental protocol :
In vivo experiments :
We performed several experiments under separately induced ulcer conditions to test the effectiveness of the herbal composition and tabulate it later. The effect of the herbal composition was compared with the known anti-ulcer drug “Omeprazole”.

Experiment 1: Effect on cold restraint ulcer (CRU) model Method: In order to prevent food droppings, adult rats with 150-175 g weight of bisexual body weight were fasted in a metal cage with a raised bottom and allowed to drink water freely. It was. Study drug was administered 45 minutes prior to animal fixation. Rats were fixed in restraint cages and kept at 4 ° C. for 2 hours in a BOD incubator (according to the method of Senay and Levine 1967). The animals were sacrificed immediately after the restraint period. The abdomen was cut open; the stomach was removed, incised along the large vagina, and the gastric lesion was observed with a Magnascope (5 × magnification).

The following random scoring systems were used to grade lesion severity and intensity:
1. Missing epithelium = 10
2. Dot and obvious bleeding = 20
3.1 or 2 ulcers = 30
4.3 or more ulcers = 40
5. Perforated ulcer = 50

The presence of these lesions was considered as a positive ulcer-induced response and was expressed as the rate of rats showing gastric lesions. Ulcer severity is expressed as the ulcer index, which is the average score of gastric lesions of all rats in one group. The term ulcer index is defined as follows:
Ulcer index (UI) = Us + Up × 10 ⁻¹
Where Us = mean ulcer severity score, and Up = percentage protection of ulcerated animals is calculated as follows:
Protection rate = (C−T / C) × 100
Where C = number of animals showing ulcer response in control group and T = number of animals showing ulcer response in test group

The effect of the herbal composition of the present invention, hereinafter referred to as “HF”, on the Cold Restrained Ulcer Model (CRU) is shown in Table 1. The effect of the standard drug “Omeprazole” is also shown at the end of Table 1. The protection rates of the herbal composition (HF) and Omeprazole of the present invention against the CRU model are listed in Table 2 shown at the end of the description.
Conclusion : The composition of the present invention is significantly effective in the CRU model.

Experiment 2: Effect on aspirin-induced gastric ulcer model Method: Gastric ulcer was induced by aspirin according to the method of Djahanguiri (1969). Aspirin (150 mg / Kg) was administered orally as a suspension in gum arabic, the animals were sacrificed 5 hours after aspirin treatment, and the ulcer index was calculated along with the protective index.

The effect of HF on aspirin-induced gastric ulcer is shown in Table 3. The effect of the standard drug “Omeprazole” is also shown at the end of the table. The protection rates of the inventive herbal composition (HF) and Omeprazole against this model are listed in Table 4 shown at the end of the description.
Conclusion : The herbal composition of the present invention is effective against an aspirin-induced gastric ulcer model.

Experiment 3: Effect on histamine-induced ulcer model
Method :
1. The animals were fasted for 24 hours under free access to water.
2. The drug was administered orally 1 hour before histamine administration.
3. Histamine 0.25 mg / Kg 7 times at 30 minute intervals i. m. The guinea pig induced 100% duodenal ulceration (according to the method of Watt and Eagleton 1964).
4). The animals were sacrificed half an hour after the last injection under ether anesthesia.
5. The stomach was removed with the duodenum, washed thoroughly, and examined for lesions. The ulcer index and protective index were calculated.

The effect of HF on histamine-induced duodenal ulcer is shown in Table 5. The effect of the standard drug “Omeprazole” is also shown at the end of the table. The protection rate of the herbal composition of the present invention (HF) and Omeprazole against histamine-induced duodenal ulcer is listed in Table 6 shown at the end of the description.
Conclusion : The herbal composition “HF” of the present invention shows a significant anti-ulcer effect on this model.

Experiment 4: Effects on alcohol-induced gastric ulcer in rats
Method :
1. Adult rats weighing 150-175 g of both sexes were removed and fasted for 24 hours under free access to water.
2. The test drug was administered (po) 45 minutes before alcohol administration.
3. 1 ml of cold anhydrous alcohol was administered (po) to rats (according to Wittetal).
4. Immediately after 1 hour, the animals were anesthetized, the abdomen was cut open, the stomach was removed, an incision was made along the greater curvature, and the gastric lesions were observed.
-The ulcer was examined with a Magnascope at a magnification of 5x.
Absolute ethanol lesions are seen as black-like lesions classified into plaques of various sizes, usually parallel to the main axis of the stomach.
5. The lesion length is measured and summed to give a total lesion score, then calculated and displayed as a percentage.

The effect of HF on the alcohol-induced gastric ulcer model is shown in Table 7. The effect of the standard drug “Omeprazole” is also shown at the end of the table. The protection rates of the herbal composition of the present invention (HF) and Omeprazole against the alcohol-induced ulcer model are listed in Table 8 shown at the end of the description.
Conclusion : The composition of the present invention does not show any significant effect on the alcohol-induced gastric ulcer model.

Experiment 5: Effect on pyloric ligation-induced ulcer model
Method :
1. To prevent food droppings, the animals were fasted for 24 hours in a cage with a mesh-raised bottom and allowed free access to water.
2. Rats received the vehicle in the control group and each drug in the experimental group 45 minutes before ligation.
3. The animals were anesthetized, the abdomen was cut open under the xiphoid process, and the pyloric portion of the stomach was lifted and ligated slightly to avoid any damage to nearby blood vessels (following the method of Shay et al. 1945).
4). The animals were sutured and kept for 4 hours under free access to water.
5.4 hours later, the animals were sacrificed under ether anesthesia, and the stomach was examined by incision along the greater curvature.
6). The stomach was thoroughly washed and the ulcer index was scored like other ulcer models.
The effect of HF on pyloric ligation-induced ulcers is shown in Table 9. The effect of the standard drug “Omeprazole” is also shown at the end of the description in Table 9. The protection rate of the herbal composition of the present invention (HF) and Omeprazole against pyloric ligation-induced ulcers is listed in Table 10 shown at the end of the description.
Conclusion : In comparison, the herbal composition shows high anti-ulcer activity. The anti-ulcer activity of the herbal composition is higher than that of Omeprazole.

Experiment 6: Production of herbs and compositions
Method :
All herbs are washed, dried and crushed for animal testing purposes. All herbs are removed in proportions as indicated in Table 11. Add water, boil and concentrate to the proper consistency. The ingredients of a standard “herbal composition” (HF) and their proportions according to one aspect of the present invention are listed in Table 11 shown at the end of the description. The parts of herbs that can be used are also listed. The placebo formulation is adjusted to resemble the taste, smell and appearance of the Ayurvedic herbal formulation.

Claims (23)

  Extracts obtained essentially from plant parts of Aegle marmelos and Withania somnifra and optionally from plant parts of Blechnum orintale, Vitis vinifera, Feronia elephantum, Punica grantum, Ziniber officnale, Piper nigrum, Piper longum and Azadirachta indica A novel synergistic herb composition for the treatment of gastric ulcer comprising together with more than one pharmaceutically acceptable additive / carrier.   Essentially comprising 4-10% by weight of an extract of Aegle marmelos and 4-11% by weight of an extract of Withania somnifra, optionally 5-8% by weight of an extract of Blechnum orintale, 5-11% of an extract of Vitis vinifera Wt%, Feronia elephantum extract 5-9 wt%, Punica grantum extract 8-11 wt%, Ziniber officnale extract 4-9 wt%, Piper nigrum extract 2-11 wt%, Piper longum extract A composition according to claim 1, comprising 8-12% by weight extract and 2-11% by weight extract of Azadirachta indica together with one or more pharmaceutically acceptable additives / carriers.   The composition of claim 1, wherein the extract is an aqueous extract.   The composition according to claim 1, wherein the plant parts of Aegle marmelos, Withania somnifra and Blechnum orintale are roots.   The composition according to claim 1, wherein the plant parts of Vitis vinifera, Feronia elephantum, Piper nigrum and Piper longum are fruits.   The composition according to claim 1, wherein the plant part of Punica grantum is fruit peel.   The composition according to claim 1, wherein the plant part of Ziniber officnale is a rhizome.   The composition according to claim 1, wherein the plant part of Azadirachta indica is bark.   Obtain extracts from plant parts of essentially Aegle marmelos and Withania somnifra and optionally from plant parts of Blechnum orintale, Vitis vinifera, Feronia elephantum, Punica grantum, Ziniber officnale, Piper nigrum, Piper longum and Azadirachta indica A process for the production of a novel synergistic herb composition for the treatment of gastric ulcer, comprising mixing with one or more pharmaceutically acceptable additives / carriers.   4-10% by weight of an extract of Aegle marmelos and 4-11% by weight of an extract of Withania somnifra, optionally 5-8% by weight of an extract of Blechnum orintale, 5-11% by weight of an extract of Vitis vinifera, Feronia elephantum extract 5-9%, Punica grantum extract 8-11%, Ziniber officnale extract 4-9%, Piper nigrum extract 2-11%, Piper longum extract 8 10. Obtained by crushing -12 wt% and Azadirachta indica extract 2-11 wt% into a fine paste and mixing them with one or more pharmaceutically acceptable additives / carriers. the method of.   The method according to claim 10, wherein the extract is an aqueous extract.   11. The method according to claim 10, wherein the plant parts of Aegle marmelos, Withania somnifra and Blechnum orintale are roots.   The method according to claim 10, wherein the plant parts of Vitis vinifera, Feronia elephantum, Piper nigrum and Piper longum are fruits.   The method according to claim 10, wherein the plant part of Punica grantum is fruit skin.   The method according to claim 10, wherein the plant part of Ziniber officnale is a rhizome.   The method according to claim 10, wherein the plant part of Azadirachta indica is bark.   Essentially comprising 4-10% by weight of an extract of Aegle marmelos and 4-11% by weight of an extract of Withania somnifra, optionally 5-8% by weight of an extract of Blechnum orintale, 5-11% of an extract of Vitis vinifera Wt%, Feronia elephantum extract 5-9 wt%, Punica grantum extract 8-11 wt%, Ziniber officnale extract 4-9 wt%, Piper nigrum extract 2-11 wt%, Piper longum extract Administering an effective amount of a synergistic herb composition comprising 8-12 wt% extract and 2-11 wt% Azadirachta indica extract together with one or more pharmaceutically acceptable additives / carriers A method for treating gastric ulcer in a subject comprising the steps of:   The method according to claim 17, wherein the subject is a mammal including a human.   18. The method of claim 17, wherein 50-100 mg of composition is administered to a subject per kg body weight.   18. The method of claim 17, wherein the composition takes a tablet, capsule, syrup or any other form known in the art.   18. A method according to claim 17, wherein the composition is administered orally, intramuscularly and any other conventional manner.   The method according to claim 17, wherein the composition is used for therapeutic and prophylactic treatment of gastric ulcer.   18. The method of claim 17, wherein the subject is administered in a single bolus dose or multiple doses.