GB2364640A - Composition for the treatment of peptic ulcer comprising American ginseng - Google Patents
Composition for the treatment of peptic ulcer comprising American ginseng Download PDFInfo
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- GB2364640A GB2364640A GB0017046A GB0017046A GB2364640A GB 2364640 A GB2364640 A GB 2364640A GB 0017046 A GB0017046 A GB 0017046A GB 0017046 A GB0017046 A GB 0017046A GB 2364640 A GB2364640 A GB 2364640A
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- american ginseng
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- 235000003140 Panax quinquefolius Nutrition 0.000 title claims abstract description 71
- 240000005373 Panax quinquefolius Species 0.000 title claims abstract description 66
- 208000008469 Peptic Ulcer Diseases 0.000 title claims abstract description 26
- 208000011906 peptic ulcer disease Diseases 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims description 8
- 239000000284 extract Substances 0.000 claims abstract description 104
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 87
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000007864 aqueous solution Substances 0.000 claims abstract description 16
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims abstract description 9
- 230000001376 precipitating effect Effects 0.000 claims abstract description 6
- 239000000706 filtrate Substances 0.000 claims description 33
- 239000000126 substance Substances 0.000 claims description 18
- 239000012528 membrane Substances 0.000 claims description 16
- 238000000108 ultra-filtration Methods 0.000 claims description 16
- 239000012465 retentate Substances 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 238000000502 dialysis Methods 0.000 claims description 6
- 239000006228 supernatant Substances 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 230000002441 reversible effect Effects 0.000 claims description 5
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000000718 duodenal ulcer Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims 2
- 201000005917 gastric ulcer Diseases 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 10
- 230000002467 anti-pepsin effect Effects 0.000 abstract description 5
- 235000008434 ginseng Nutrition 0.000 description 12
- 208000025865 Ulcer Diseases 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 235000002789 Panax ginseng Nutrition 0.000 description 9
- 240000004371 Panax ginseng Species 0.000 description 7
- 231100000397 ulcer Toxicity 0.000 description 7
- 244000131316 Panax pseudoginseng Species 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 5
- 230000000740 bleeding effect Effects 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000036269 ulceration Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 235000015961 tonic Nutrition 0.000 description 3
- 230000001256 tonic effect Effects 0.000 description 3
- 241000208340 Araliaceae Species 0.000 description 2
- 241000208343 Panax Species 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000013289 male long evans rat Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 229940121819 ATPase inhibitor Drugs 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 235000002791 Panax Nutrition 0.000 description 1
- 235000003181 Panax pseudoginseng Nutrition 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000362 adenosine triphosphatase inhibitor Substances 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 230000007074 memory dysfunction Effects 0.000 description 1
- LZCOQTDXKCNBEE-IKIFYQGPSA-N methscopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-IKIFYQGPSA-N 0.000 description 1
- 229960001383 methylscopolamine Drugs 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 235000008935 nutritious Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 238000009160 phytotherapy Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a pharmaceutical composition for preventing and/or treating peptic ulcer, including American ginseng or the extract thereof, and a method for preparing American ginseng extract, said method including extracting American ginseng with water or ethanol aqueous solution, and then ultrafiltrating, dialyzing, precipitating with ethanol, or performing reverse phase chromatography to obtain various fractions of extract with anti-peptic ulcer effect.
Description
<Desc/Clms Page number 1> ANTI-ULCER PHARMACEUTICAL COMPOSITION AND THE PREPARATION THEREOF BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to pharmaceutical compositions useful for the prevention and/or treatment of peptic ulcer diseases. More particularly, it relates to the use of American ginseng or the extract thereof as the active ingredient for the prevention and treatment of peptic ulcer diseases.
Description of the Related Arts American ginseng (Panax quip quefolium L.) is one species of Araliaceae, which is the North American variety of ginseng native to the United States and Canada. The Panax plants in Araliaceae, such as Panax ginseng, Panax quinquefolium, Panax pseudo-ginseng etc, have been used as a form of tonic in Chinese medicine for a long period of time, and Panax ginseng is traditionally considered a valuable medicinal material in China, Japan and Korea. After harvesting, Panax ginseng with good quality is generally treated with boiling water or steam to give red ginseng. Panax ginseng which has been dried by hot air or sunlight is called white ginseng or unprocessed ginseng. The American ginseng is an herbaceous perennial and its root is mainly used as a nutritious tonic agent. Its morphology is similar to Panax ginseng, but has less fiber-like or lateral roots. At present, the American ginseng is artificially cultivated
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in the United States, Mainland China and Russia. Many reports have shown some components of American ginseng are similar to Panax ginseng, including several kinds of ginseng saponins, oligosaccharides, volatile oils, amino acids, vitamins and trace elements. It is traditionally believed that both American ginseng and Panax ginseng possess effects of increasing physical strength, nourishing and preserving health, and prolonging life. Thus, they are regarded as mild tonics used for daily dietary or medicinal remedy.
Recently, a number of scientific reports show that the American ginseng indeed possesses a variety of physiological or pharmaceutical activities, including anti-aging (Xiao P.G. et. al., 1993, Journal of Ethnopharmacology 38 (2-3) :167-75) ; preventing atherosclerosis and hyperlipidemia (Li J. et. al., 1999, Life Science 64 (1) :53-62) ; protecting liver from injury (Yoshikawa, M. et. al., 1998, Chemical and Pharmaceutical Bulletin 46(4):647-54); enhancing the function of cardiovascular system (Kwan C. Y., 1995, Clinical and Experimental Pharmacology and Physiology-supplement 1:S297-9; Yang S., 1992, China Journal of Chinese Material Medica 17(9):555-7 and US Patent No. 4,708,949); preventing memory dysfunction and dementia (Benishin C. G., 1991, Pharmacology 42(4):223-9; Li Z. et. al., 1999, Journal of Pharmacy and Pharmacology 51(4):435-40; Lewis R. et. al., 1999, Phytotherapy Research 13 (1) :59-64) ; decreasing hyperglycemia (Oshima Y. et. al., 1987, Journal of Natural Products 50(2):188-90; Martinez S. and Staba E. J., 1984, Japanese Journal
<Desc/Clms Page number 3>
of Pharmacology 35 (2) :79-85) ; inhibition of breast cancer cells (Duda R. B. et. al., 1996, Annals of Surgical Oncology 3(6):515-20); enhancing physical strength; antiviral activity (US Patent No. 5, 071, 839); anti-oxidation; decreasing the side effects of anticancer chemotherapy and radiotherapy (US Patent No. 4, 9 4 5, 115) ; modulating gastric digestion (Yuan C. S. et. al., 1998, American Journal of Chinese Medicine 26(1):47-55); and increasing the immune function (US Patent No. 4,795,742) etc.
Recently, the population with gastrointestinal diseases has been increasing, especially in highly developmental countries. The causes of peptic ulcers include unrelieved daily pressure; excessive alcohol irritation; the side effects of drugs, such as aspirin or non-steroid anti- inflammatory drugs; or Helicobacter pyroli infection. The predominant drugs used to treat peptic ulcers include muscarinic antagonists, such as methscopolamine bromide; H2 blockers, such as cimetidine; antacids, such as aluminum hydroxide or magnesium hydroxide; H+/K+ ATPase inhibitor, such as omeprazole; antibacterial drugs, such as admixture of amoxicillin and metronidazole. Such drugs may be classified into two categories: one is used for physical protection of gastric mucosa to mitigate the irritation of the gastric acid to.the mucosa ulcer site; the other is used for chemically inhibiting the secretion of the gastric acid, to avoid ulceration produced from excessive gastric acid erosion. The prevalence of peptic ulcers and
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their high rate of recurrence may be due to patients' life style or seasonal change and many patients repeatedly suffer from peptic ulcers. Thus, there is a need for a safe, mild and effective drug for treating and preventing peptic ulcers.
SUMMARY OF THE INVENTION It is an object of the present invention to provide pharmaceutical compositions which are effective in preventing and/or treating peptic ulcer diseases, comprising an effective amount of American ginseng and/or the extract thereof, and a physiologically or pharmaceutically acceptable carrier.
An additional object of the present invention is to provide a process of preparing the extracts of the American ginseng described above, comprising the steps of (a) extracting American ginseng with a solvent with a polarity higher than 0.88 to obtain an extract; (b) filtering the extract to obtain a filtrate; and (c) centrifuging the filtrate to obtain a supernatant (total extract).
The preparation process according to the present invention may further comprise the means of ultrafiltrating, dialyzing, precipitating with ethanol, or performing reverse phase chromatography, to obtain certain fractions of American ginseng extract.
Another object of the present invention is to provide methods for preventing and/or treating a patient suffering from peptic ulcer, comprising administering an effective amount of American ginseng and/or the extracts thereof to said patient.
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DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, there is provided a process of preparing the pharmaceutical compositions comprising American ginseng or the extract thereof. First, American ginseng is extracted with a solvent with a polarity higher than 0.88 to obtain an extract. Suitable solvent includes water, ethanol, methanol or the mixtures thereof, preferably water or ethanol, and more preferably 10% - 80% ethanol aqueous solution. Next, the extract is filtered to remove plant residues, and then centrifuged to remove microparticles and impurities. The resulting supernatant (total extract) is concentrated into an appropriate concentration, and then further treated by one or more of the following processes: ultrafiltrating, dialyzing, precipitating with ethanol, or performing reverse phase chromatography, to obtain various fractions of American ginseng extract.
In the process described above, ultrafiltrating is a step in which the total extract is filtered by an ultrafiltration membrane with molecular weight cut off 1,000 or 3,000 to give a retentate and a filtrate. Dialyzing is a step in which the total extract is dialyzed by a membrane or dialysis bag with molecular weight cut off 500 to remove smaller molecules. Precipitating with ethanol is a step in which the filtrate obtained from ultrafiltration is concentrated to dryness and then dissolved with 50% - 100% ethanol to obtain the soluble portion. Performing reverse phase chromatography is a step in which the filtrate obtained from ultrafiltration is loaded onto a reverse phase polyaromatic resin column, such as Diaion HP-20 (Sigma, Cat.
<Desc/Clms Page number 6>
No. I-3605), to elute the active fraction of American ginseng extract.
All American ginseng extracts obtained from various processes of the present invention possess an anti-peptic ulcer effect. Moreover, these extracts may be added to a physiologically acceptable carrier and/or formulated with 'a pharmaceutically acceptable excipient to obtain a pharmaceutical composition which is effective in treating or preventing peptic ulcers. The term "peptic ulcer" used hereinbefore and hereinafter refers to gastric ulcers and/or duodenal ulcers.
Without intending to limit it in any manner, the present invention will be further illustrated by the following examples which are associated with the design of the extraction step (s) and the assessment of pharmacological activity.
EXAMPLE 1 2,000 ml of deionized water was added to 200 g of chopped American ginseng and then heated to boiling and further refluxed for 1 hour. The decoction was filtered through sieve gauge No. 200 (sieve pore 0.074 mm), and the filtrate (first filtrate) was collected. An additional 2,000 ml of deionized water was added to the residue of the American ginseng described above, and was refluxed and filtered as described above to give the second filtrate. These two filtrates were combined and centrifuged at 10,000 rpm for 30 minutes to remove microparticles and impurities. The supernatant (total extract) was then filtered through the ultrafiltration membrane with molecular weight cut off 1,000
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(Amicon, Cat. No. SlY1) to remove substances with molecular weight less than 1,000 dalton. The retentate containing substances with molecular weight greater than 1,000 dalton was concentrated under reduced pressure to give the extract I. The filtrate containing substances with molecular weight less than 1,000 dalton was concentrated to dryness, and then 90% ethanol solution was added to dissolve those substances.
The ethanol solution was filtered (Advantec No. 2) to obtain the soluble portion, and the resulting soluble portion was added into the extract I described above. The mixture was concentrated under reduced pressure to give the extract II. EXAMPLE 2 The total extract described in EXAMPLE 1 was treated through an ultrafiltration membrane with molecular weight cut off 3,000 (Amicon, Cat. No. S1Y3) to remove substances with molecular weight less than 3,000 dalton. The retentate containing substances with molecular weight greater than 3,000 dalton was concentrated under reduced pressure to give the extract III. The filtrate containing substances with molecular weight less than 3,000 dalton was loaded onto a column packed with Diaion HP-20 resin (Sigma, Cat. No. I- 3605). The column was first eluted with deionized water until the eluate was colorless, and then eluted with 950 ethanol and the eluate was collected. The 95% ethanol eluate was added into the extract III described above. The mixture was concentrated under reduced pressure to give the extract IV.
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EXAMPLE The total extract described in EXAMPLE 1 was loaded in a dialysis bag with molecular weight cut off 500 (Spectra/Por , Cat. No. 131 057). Both ends of the bag were sealed with clamps. The bag was placed in a bucket contained deionized water, in which the ratio of the supernatant and deionized water was 1:10. The total extract was dialyzed at 4 C with stirring thrice each for 20 hours. The solution remaining in dialysis bag was collected and concentrated under reduced pressure to give the extract.
EXAMPLE 4 1,000 ml of 80% ethanol solution was added to 100 g of chopped American ginseng and was heated to boiling and further refluxed for 1 hour. The decoction was filtered through sieve gauge No. 200, and the filtrate (first filtrate) was collected. An additional 1,000 ml of 80% ethanol solution was added to the residue of the ginseng and extracted as described above, to give the second filtrate. These two filtrates were combined and concentrated under reduced pressure to give the extract V.
EXAMPLE 5 Assessment of the pharrma n#l ogi c.a 1 a i vi tar o anti-peptic ulcer: The anti-peptic ulcer activity of American ginseng was assessed using the methods described by Robert A. et. al. (1979, Gastroenterology 77:433-443), and Takagi I. and Okabe S. .(1968, Japan J. Pharmacol. 18:9-18), which is summarized below.
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(1) The assessment of stress-induced ulcer: Male Long Evans rats, weighing 150 20 g, were administrated American ginseng extracts orally after being fasted for 18 hours, while the control rats were administrated the same volume of distilled water orally. After 1 hour, the rats were placed in a holder and partially immersed in water at 22 - 24 C for 4 hours. The rats were then sacrificed and their stomachs were opened along the greater curvature for evaluation of the degree of ulceration. Gastric ulceration was scored according to an arbitrary system: 0 = no bleeding 1 = spot bleeding 2 = slight bleeding 3 = severe bleeding and half stomach bloodstained 4 = very severe bleeding and entire stomach bloodstained
<Desc/Clms Page number 10>
Table 1. Effect of American ginseng extracts on stress- induced ulcer in rat. Treatment Dose N Inhibition (%)a (g/kg) Total Extract 4 10 27.5f2.4 Extract I 4 10 42.5 3.6 Extract II 4 6 37.5t5.1 Extract III 4. 10 42.5f3.6 Extract IV 4 6 51.2 3.8 Extract V 4 4 37.5 6.3
a: The inhibition rate (%) is calculated by the following equation: [(score of control animal)-(score of experimental animal)]/ (score of control animal) x 1000.
A11 the ulcer scores of the control rats were 4. (2) The assessment of ethanol-induced ulcer: Male Long Evans rats, weighing 150 20 g, were administrated American ginseng extracts orally after being fasted for 18 hours, while the control rats were administrated the same volume of distilled water orally. After 15 minutes, the rats were administered 1 ml of absolute ethanol. After 1 hour, the rats were sacrificed and gastric ulceration was scored according to an arbitrary system:
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0 = no lesions 1 = hyperaemia 2 = one or two slight lesions 3 = more than two slight lesions or severe lesions 4 = very severe lesions
Table 2. Effect of American ginseng extract on ethanolinduced ulcer in rat. Treatment Dose N Inhibition (o)' (g/kg) Total Extract 4 10 50.0 0.0 Extract 1 4 10 50.0 0.0 Extract 11 4 6 45.8 3.8 Extract 111 4 10 40.0 5.2
a: The inhibition rate (%) is calculated by the following equation: [(score of control animal)-(score of experimental animal)]/ (score of control animal) x 1000.
All the ulcer scores of the control rats were 4.
The results of pharmacological assessment shown in Tables 1 and 2 reveal that American ginseng extracts of the present invention possess excellent inhibition effects of gastric ulcers induced by stress and alcohol. In addition, according to the present invention, the American ginseng extracted with water or ethanol solution and further treated by ultrafiltration, dialysis, precipitation with ethanol, or
<Desc/Clms Page number 12>
reverse phase chromatography, possesses excellent anti- peptic ulcer effects.
While the invention has been particularly shown and described with the reference to the preferred embodiment thereof, it will be understood by those skilled in the art that various changes in form and details may be made without departing from the scope of the invention.
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Claims (1)
- WHAT I S CLAIMED IS: 1. A pharmaceutical composition for preventing and/or treating peptic ulcer, comprising: (i) an effective amount of American ginseng and/or the extract thereof; and (ii) a physiologically or pharmaceutically acceptable carrier or excipient. 2. The pharmaceutical composition according to claim 1, wherein said American ginseng is Panax quinquefolium L.. 3. The pharmaceutical composition according to claim 1, wherein said American ginseng extract is extracted with a solvent having a polarity higher than 0.88. 4. The pharmaceutical composition according to claim 3, wherein said American ginseng extract is extracted with 10% 80% ethanol aqueous solution. 5. The pharmaceutical composition according to claim 3, wherein said American ginseng extract is extracted with water. 6. The pharmaceutical composition according to claim 1, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, and filtered through an ultrafiltration membrane with molecular weight cut off 1,000 to give a retentate containing substances with molecular weight greater than<Desc/Clms Page number 14>1,000 dalton, and the retentate being concentrated to give an extract I. 7. The pharmaceutical composition according to claim 6, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, and filtered through an ultrafiltration membrane with molecular weight cut off 1,000 to give a filtrate containing substances with molecular. weight less than 1,000 dalton, the filtrate being concentrated to dryness,' ethanol solution is added to dissolve said substances, said ethanol solution is filtered to obtain a soluble portion, said soluble portion is added into said extract I as claimed in claim 6 to obtain a mixture, and said mixture is concentrated to give an extract II. 8. The pharmaceutical composition according to claim 1, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, filtered through an ultrafiltration membrane with molecular weight cut off 3,000 to give a retentate containing substances with molecular weight greater than 3,000 dalton, and the retentate being concentrated to give an extract III. 9. The pharmaceutical composition according to claim 8, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, filtered through an ultrafiltration membrane with molecular weight cut off 3,000 to give a filtrate containing substances with molecular weight less than 3,000 dalton, the filtrate being loaded onto a reverse phase column, eluted with water, followed by 95% ethanol solution and the<Desc/Clms Page number 15>e luate is collected, and then the 95% ethanol eluate is combined with said extract III in claim 8 and concentrated to give extract IV. 10. The pharmaceutical composition according to claim 1, wherein said American ginseng extract is extracted with 30% 90% ethanol aqueous solution followed by filtration and concentration to give extract V. 11. The pharmaceutical composition according to claim 1, wherein said peptic ulcer is a gastric ulcer or duodenal ulcer. 12. A process o f preparing American ginseng and/or an extract thereof for preventing and/or treating peptic ulcers, comprising the steps of: (a) treating American ginseng with a solvent with a polarity higher than 0.88 to obtain an extract; (b) filtering said extract to obtain a filtrate; and (c) centrifuging said filtrate and collecting the supernatant to give the total extract. 13. The process according to claim 12, further comprising the step of ultrafiltrating said total extract to give a retentate and a filtrate. 14. The process according to claim 13, wherein said ultrafi.ltrating is a step in which said total extract is filtered by means of an ultrafiltration membrane with molecular weight cut off 1,000 or 3,000 to remove smaller molecules.<Desc/Clms Page number 16>15. The process according to claim 12, further comprising the step of dialyzing said total extract. 16. The process according to claim 15, wherein said dialyzing is a step in which said total extract is dialyzed by means of a dialysis membrane with molecular weight cut off 500 to remove smaller molecules. 17. The process according to claim 13, further comprising a precipitating step in which said filtrate is concentrated to dryness and then dissolved with 50% - 100% ethanol to obtain the soluble portion. 18. The process according to claim 13, further comprising the step of performing reverse phase chromatography of said filtrate. 19. The process according to claim 18, wherein said reverse phase chromatography is performing with a reverse phase polyaromatic resin column. 20. The process according to claim 12, wherein said American ginseng extract is extracted with 10% - 80% ethanol aqueous solution. 21. The process according to claim 12, wherein said American ginseng extract is extracted with water.<Desc/Clms Page number 17>22. Use of a pharmaceutical composition as claimed in any one of claims 1 to 11 in the preparation of a medicament containing an effective amount of American ginseng and/or an extract thereof for the treatment of peptic ulcer in a mammal. 23. A pharmaceutical composition substantially as described herein. 24. A process of preparing American ginseng and/or an extract thereof substantially as described herein.<Desc/Clms Page number 18>WHAT IS CLAIMED IS 1. A pharmaceutical composition for preventing and/or treating peptic ulcer, comprising: (i) an effective amount of American ginseng and/or the extract thereof; and (ii) a physiologically or pharmaceutically acceptable carrier or excipient. 2. The pharmaceutical composition according to claim 1, wherein said American ginseng is Panax quinquefolium L.. 3. The pharmaceutical composition according to claim 1, wherein said American ginseng extract is extracted with a solvent having a polarity higher than 0.88. 4. The pharmaceutical composition according to claim 3, wherein said American ginseng extract is extracted with 10% 80% ethanol aqueous solution. 5. The pharmaceutical composition according to claim 3, wherein said American ginseng extract is extracted with water. 6. The pharmaceutical composition according to claim 1, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, and filtered through an ultrafiltration membrane with molecular weight cut off 1,000 to give a retentate containing substances with molecular weight greater than<Desc/Clms Page number 19>1,000 dalton, and the retentate being concentrated to give an extract I. 7. The pharmaceutical composition according to claim 6, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, and filtered through an ultrafiltration membrane with molecular weight cut off 1,000 to give a filtrate containing substances with molecular. weight less than 1,000 dalton, the filtrate being concentrated to dryness,' ethanol solution is added to dissolve said substances, said ethanol solution is filtered to obtain a soluble portion, said soluble portion is added into said extract I as claimed in claim 6 to obtain a mixture, and said mixture is concentrated to give an extract II. 8. The pharmaceutical composition according to claim 1, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, filtered through an ultrafiltration membrane with molecular weight cut off 3,000 to give a retentate containing substances with molecular weight greater than 3,000 dalton, and the retentate being concentrated to give an extract III. 9. The pharmaceutical composition according to claim 8, wherein said American ginseng extract is extracted with water or 10% - 80% ethanol aqueous solution, centrifuged, filtered through an ultrafiltration membrane with molecular weight cut off 3,000 to give a filtrate containing substances with molecular weight less than 3,000 dalton, the filtrate being loaded onto a reverse phase column, eluted with water, followed by 95% ethanol solution and the<Desc/Clms Page number 20>elua t e is collected, and then the 95% ethanol eluate is combined with said extract III in claim 8 and concentrated to give extract IV. 10. The pharmaceutical composition according to claim 1, wherein said American ginseng.extract is extracted with 300 90% ethanol aqueous solution followed by filtration and concentration to give extract V. 11. The pharmaceutical composition according to claim 1, wherein said peptic ulcer is a gastric ulcer or duodenal ulcer. 12. A process of obtaining American ginseng extract for a pharmaceutical composition as claimed in claim l for preventing and/or treating peptic ulcers, comprising the steps of: (a) treating American ginseng with a solvent with a polarity higher than 0.88 to obtain an extract; (b) filtering said extract to obtain a filtrate; and (c) centrifuging said filtrate and collecting the supernatant to give the total extract. 13. The process according to claim 12, further comprising the step of ultrafiltrating said total extract to give a retentate and a filtrate. 14. The process according to claim 13, wherein said ultrafi.ltrating is a step in which said total extract is filtered by means of an ultrafiltration membrane with molecular weight cut off 1,000 or 3,000 to remove smaller molecules.<Desc/Clms Page number 21>15. The process according to claim 12, further comprising the step of dialyzing said total extract. 16. The process according to claim 15, wherein said dialyzing is a step in which said total extract is dialyzed by means of a dialysis membrane with molecular weight cut off 500 to remove smaller molecules. 17. The process according to claim 13, further comprising a precipitating step in which said filtrate is concentrated to dryness and then dissolved with 50% - 100% ethanol to obtain the soluble portion. 18. The process according to claim 13, further comprising the step of performing reverse phase chromatography of said filtrate. 19. The process according to claim 18, wherein said reverse phase chromatography is performing with a reverse phase polyaromatic resin column. 20. The process according to, claim 12, wherein said American ginseng extract is extracted with 10% - 80% ethanol aqueous solution. 21. The process according to claim 12, wherein said American ginseng extract is extracted with water.<Desc/Clms Page number 22>22. Use of a pharmaceutical composition as claimed in any one of claims 1 to 11 in the preparation of a medicament containing an effective amount of American ginseng and/or an extract thereof for the treatment of peptic ulcer in a mammal. 23. A pharmaceutical composition substantially as described herein with reference to claim 1. 24. A process of preparing American ginseng and/or an extract thereof substantially as described herein with reference to claim 12.
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GB0017046A GB2364640B (en) | 2000-07-11 | 2000-07-11 | Anti-ulcer pharmaceutical composition and the preparation thereof |
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GB0017046A GB2364640B (en) | 2000-07-11 | 2000-07-11 | Anti-ulcer pharmaceutical composition and the preparation thereof |
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FR2797401A1 (en) * | 2000-01-11 | 2001-02-16 | Pharmaceutical Ind Tech & Dev | Compositions comprising American ginseng and/or its extract for the prevention and treatment of gastro-duodenal ulcers |
CN102793160A (en) * | 2011-05-28 | 2012-11-28 | 张文知 | Method for preparing American ginseng extract powder |
CN104688897A (en) * | 2015-03-03 | 2015-06-10 | 张远强 | Pharmaceutical composition for treating oral ulcer and preparation method thereof |
CN114028836A (en) * | 2021-09-26 | 2022-02-11 | 承创(常熟)医药科技有限公司 | Method for removing pigment and odor from plant extract |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN109394793A (en) * | 2018-12-29 | 2019-03-01 | 桂林医学院 | The Formica fusca extract and preparation method thereof for treating damp-heat type vulvitis |
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US4708949A (en) * | 1985-09-24 | 1987-11-24 | Yaguang Liu | Therapeutic composition from plant extracts |
US4795742A (en) * | 1985-09-24 | 1989-01-03 | Yaguang Liu | Therapeutic composition from plant extracts |
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WO1999030725A1 (en) * | 1997-12-12 | 1999-06-24 | C.V. Technologies Inc. | Processes of making north american ginseng fractions, products containing them, and use as immunomodulators |
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US4945115A (en) * | 1985-05-09 | 1990-07-31 | Yaguang Liu | Process for preparing ferulic acid |
US4708949A (en) * | 1985-09-24 | 1987-11-24 | Yaguang Liu | Therapeutic composition from plant extracts |
US4795742A (en) * | 1985-09-24 | 1989-01-03 | Yaguang Liu | Therapeutic composition from plant extracts |
US5071839A (en) * | 1987-11-02 | 1991-12-10 | Yaguang Liu | Safe pharmaceutical composition for decreasing side effects of antiviral drugs and increasing the immune function (SDI) II |
WO1999030725A1 (en) * | 1997-12-12 | 1999-06-24 | C.V. Technologies Inc. | Processes of making north american ginseng fractions, products containing them, and use as immunomodulators |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2797401A1 (en) * | 2000-01-11 | 2001-02-16 | Pharmaceutical Ind Tech & Dev | Compositions comprising American ginseng and/or its extract for the prevention and treatment of gastro-duodenal ulcers |
US6800304B2 (en) | 2000-01-11 | 2004-10-05 | Pharmaceutical Industry Technology And Development Center | Anti-ulcer pharmaceutical composition and the preparation thereof |
US6962719B1 (en) | 2000-01-11 | 2005-11-08 | Pharmaceutical Industry Technology And Development Center | Anti-ulcer pharmaceutical composition and the preparation thereof |
US6991815B2 (en) | 2000-01-11 | 2006-01-31 | Medical And Pharmaceutical Industry Technology And Development Center | Anti-ulcer pharmaceutical composition and the preparation thereof |
CN102793160A (en) * | 2011-05-28 | 2012-11-28 | 张文知 | Method for preparing American ginseng extract powder |
CN104688897A (en) * | 2015-03-03 | 2015-06-10 | 张远强 | Pharmaceutical composition for treating oral ulcer and preparation method thereof |
CN114028836A (en) * | 2021-09-26 | 2022-02-11 | 承创(常熟)医药科技有限公司 | Method for removing pigment and odor from plant extract |
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GB0017046D0 (en) | 2000-08-30 |
GB2364640B (en) | 2002-12-04 |
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