CN111714521B - Periplaneta americana intestinal flora metabolite extract, preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products - Google Patents
Periplaneta americana intestinal flora metabolite extract, preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products Download PDFInfo
- Publication number
- CN111714521B CN111714521B CN202010640421.6A CN202010640421A CN111714521B CN 111714521 B CN111714521 B CN 111714521B CN 202010640421 A CN202010640421 A CN 202010640421A CN 111714521 B CN111714521 B CN 111714521B
- Authority
- CN
- China
- Prior art keywords
- extract
- periplaneta americana
- intestinal flora
- preparing
- butanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000284 extract Substances 0.000 title claims abstract description 104
- 241000238675 Periplaneta americana Species 0.000 title claims abstract description 92
- 230000000968 intestinal effect Effects 0.000 title claims abstract description 51
- 239000002207 metabolite Substances 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 230000003110 anti-inflammatory effect Effects 0.000 title claims abstract description 20
- 230000000767 anti-ulcer Effects 0.000 title claims abstract description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 47
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims abstract description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000003208 petroleum Substances 0.000 claims abstract description 23
- 239000006185 dispersion Substances 0.000 claims abstract description 21
- 238000000605 extraction Methods 0.000 claims abstract description 17
- 210000003608 fece Anatomy 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000001914 filtration Methods 0.000 claims abstract description 11
- 238000010992 reflux Methods 0.000 claims abstract description 9
- 239000002021 butanolic extract Substances 0.000 claims abstract description 5
- 239000002024 ethyl acetate extract Substances 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims description 20
- 239000000706 filtrate Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 229940127557 pharmaceutical product Drugs 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 27
- 230000000694 effects Effects 0.000 abstract description 15
- 239000002994 raw material Substances 0.000 abstract description 10
- 229940126680 traditional chinese medicines Drugs 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 19
- 239000000843 powder Substances 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 14
- 239000003814 drug Substances 0.000 description 12
- 230000002550 fecal effect Effects 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 208000025865 Ulcer Diseases 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 208000007107 Stomach Ulcer Diseases 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000002496 gastric effect Effects 0.000 description 8
- 201000005917 gastric ulcer Diseases 0.000 description 8
- 238000005303 weighing Methods 0.000 description 8
- 239000002034 butanolic fraction Substances 0.000 description 7
- 239000002038 ethyl acetate fraction Substances 0.000 description 7
- 230000008961 swelling Effects 0.000 description 7
- 231100000397 ulcer Toxicity 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 125000001033 ether group Chemical group 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 238000010298 pulverizing process Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000012449 Kunming mouse Methods 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002481 ethanol extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000036269 ulceration Effects 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 241000223218 Fusarium Species 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229910021485 fumed silica Inorganic materials 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000009290 xinmailong Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
- A61K35/64—Insects, e.g. bees, wasps or fleas
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Insects & Arthropods (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a periplaneta americana intestinal flora metabolite extract, a preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products. The extract is prepared from periplaneta americana feces as a raw material by ethanol reflux extraction, filtration and concentration to prepare an extract, water dispersion, petroleum ether, ethyl acetate and n-butanol extraction, and then ethyl acetate extract and n-butanol extract are collected, so that the extract has the effects of anti-inflammatory and anti-ulcer, and the efficacy is superior to that of the periplaneta americana body extract.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a periplaneta americana intestinal flora metabolite extract, a preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products.
Background
The American cockroach (Periplaneta americana L.) is a sickle insect belonging to the family Fusarium, the medical history of the American cockroach can be traced to Shennong's herbal meridian, and the American cockroach is recorded in Hunan province Chinese medicinal material standard (2009 edition) at present, and has the effects of strengthening spleen, eliminating sore, promoting blood circulation, dredging collaterals, inducing diuresis, reducing edema, healing sore and promoting granulation. In recent years, researchers have developed researches on chemical components, biological activities and the like of the periplaneta americana, and developed preparations such as Xinmailong injection, rehabilitation new liquid, ganlong capsules, xiaozhen Yiganpian and the like, so that the medicinal value of the periplaneta americana is improved.
In China, the animal intestinal flora metabolite, namely the excrement, has a long history of taking medicines. However, because people have difficulty in sensory acceptance of the fecal traditional Chinese medicine, the application of the fecal traditional Chinese medicine is more limited, so the periplaneta americana feces is still regarded as waste or is only used in fertilizers and feeds at present.
Gastric ulcer is a common digestive tract disease, and is caused by gastric mucosa barrier disruption and self-digestion of gastric mucosa by gastric acid and pepsin, and pathogenic factors include nonsteroidal anti-inflammatory drugs, alcohol, conditional stress, helicobacter pylori and the like. Inflammation is a complex defensive response of organisms with vascular systems to damaging factors, manifested clinically as redness, swelling, heat and pain and dysfunction at the site of inflammation, possibly accompanied by varying degrees of systemic response. Both are common clinical diseases. There is no report on the use of periplaneta americana intestinal flora metabolite extracts for the preparation of anti-ulcer or anti-inflammatory products.
Disclosure of Invention
Aiming at the problem that the American cockroach intestinal flora metabolite is not used for preparing anti-ulcer or anti-inflammatory products at present, the invention provides a preparation method of the American cockroach intestinal flora metabolite extract.
The invention also provides a periplaneta americana intestinal flora metabolite extract.
The invention also provides an application of the periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory or anti-ulcer products.
In order to achieve the above purpose, the embodiment of the invention adopts the following technical scheme:
a method for preparing a periplaneta americana intestinal flora metabolite extract comprises the steps of reflux-extracting periplaneta americana excrement by using 20-90% (v/v) ethanol water solution, filtering, preparing the obtained filtrate into an extract, and dispersing the extract in water to prepare a dispersion liquid; extracting the dispersion liquid with petroleum ether, ethyl acetate and n-butanol in sequence, and collecting ethyl acetate extract and n-butanol extract.
Experiments prove that the periplaneta americana intestinal flora metabolite extract obtained by the preparation method disclosed by the invention has a remarkable treatment effect on mice with gastric ulcer models, has a remarkable inhibition effect on auricle swelling of the mice caused by dimethylbenzene, and shows that the periplaneta americana intestinal flora metabolite extract obtained by the preparation method has the effects of resisting inflammation and ulcer, and can be used for preparing corresponding products, so that the periplaneta americana has higher medicinal added value.
Preferably, the reflux extraction is carried out for 1 to 3 times, each time for 1 to 3 hours.
Preferably, the preparation method of the extract comprises the following steps: concentrating under reduced pressure at 55-75deg.C to obtain the extract. Concentration under these conditions allows recovery of all ethanol.
Preferably, the petroleum ether is petroleum ether at 60-90 ℃.
Preferably, the extraction is carried out by extracting with petroleum ether, ethyl acetate and n-butanol for 3-5 times respectively, and combining the extracts of each solvent.
Preferably, the mass of the water is 3-10 times of the mass of the extract.
Preferably, the volumes of petroleum ether, ethyl acetate and n-butanol are respectively 1 to 3 times of the volume of water.
Preferably, the preparation method further comprises concentrating and drying the ethyl acetate extract and the n-butanol extract, and drying to obtain an ethyl acetate part and an n-butanol part, which are more convenient to store, use and further process into a preparation than the extract.
The embodiment of the invention also provides the periplaneta americana intestinal flora metabolite extract, which is prepared by the preparation method of the periplaneta americana intestinal flora metabolite extract.
The embodiment of the invention also provides application of the periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory and anti-ulcer products.
The periplaneta americana intestinal flora metabolite extract has anti-inflammatory and anti-ulcer effects, can be used for preventing and treating inflammation and gastric ulcer, and can effectively improve corresponding symptoms.
Preferably, the product is a pharmaceutical product. The periplaneta americana intestinal flora metabolite extract can be prepared into medicines and can be clinically used for patients suffering from inflammation or gastric ulcer. The dosage forms of the medicine include, but are not limited to, tablets, granules, capsules, powder, oral liquid and the like.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention. The following examples were carried out under the condition that the American cockroach fecal sample was taken from the GAP culture base of American cockroach, stone mountain, of the pharmaceutical Co., ltd. Of Yunnan, and the feeding condition of the American cockroach was strictly carried out according to GAP standard, and the main ingredient of the feed was bean ingredient.
Example 1
The embodiment of the invention provides a periplaneta americana intestinal flora metabolite extract, which is prepared by the following steps: the periplaneta americana faeces is taken as a raw material, crushed and sieved by a 20-mesh sieve to obtain the periplaneta americana faeces coarse powder. Weighing 1kg of periplaneta americana fecal coarse powder, adding 5L of 20% (v/v) ethanol water solution, carrying out reflux extraction for 2 times, extracting for 1.5 hours each time, filtering, combining filtrate, and recovering ethanol under reduced pressure at 55 ℃ to obtain extract; adding 3 times of water into the obtained extract according to the mass ratio (m/m), stirring and dispersing uniformly, dispersing the dispersion, sequentially extracting the dispersion with petroleum ether (60-90 ℃) which is 1 time of the volume of the dispersion, ethyl acetate and n-butanol, extracting each solvent for 3 times, respectively merging the extracts of the solvents, concentrating and recovering the solvents, and drying to obtain a petroleum ether part, an ethyl acetate part and an n-butanol part of the total extract extracted by the organic solvent and a water-soluble part remained after the n-butanol extraction; the ethyl acetate fraction and the n-butanol fraction were collected and mixed to obtain 78.26g of an extract.
Example 2
The embodiment of the invention provides a periplaneta americana intestinal flora metabolite extract, which is prepared by the following steps: the periplaneta americana faeces is taken as a raw material, crushed and sieved by a 20-mesh sieve to obtain the periplaneta americana faeces coarse powder. Weighing 1kg of periplaneta americana fecal coarse powder, adding 8L of 90% (v/v) ethanol water solution, carrying out reflux extraction for 2 times, extracting for 1 hour each time, filtering, combining filtrate, and recovering ethanol under reduced pressure at 75 ℃ to obtain extract; adding 5 times of water into the obtained extract according to the mass ratio (m/m), stirring and dispersing uniformly, dispersing the mixture, sequentially extracting the dispersion with petroleum ether (60-90 ℃) which is 1.5 times of the volume of the dispersion, ethyl acetate and n-butanol, extracting each solvent for 5 times, respectively merging the extracts of the solvents, concentrating and recovering the solvents, and drying to obtain a petroleum ether part, an ethyl acetate part and an n-butanol part of the total extract extracted by the organic solvent and a water-soluble part remained after the n-butanol extraction; the ethyl acetate fraction and the n-butanol fraction were collected and mixed to obtain 53.28g of an extract.
Example 3
The embodiment of the invention provides a periplaneta americana intestinal flora metabolite extract, which is prepared by the following steps: the periplaneta americana faeces is taken as a raw material, crushed and sieved by a 20-mesh sieve to obtain the periplaneta americana faeces coarse powder. Weighing 1kg of periplaneta americana fecal coarse powder, adding 12L of 50% (v/v) ethanol water solution, reflux-extracting for 3 times, extracting for 2 hours each time, filtering, mixing filtrates, and recovering ethanol under reduced pressure at 65 ℃ to obtain extract; adding 10 times of water into the obtained extract according to the mass ratio (m/m), stirring and dispersing uniformly, dispersing the dispersion, sequentially extracting the dispersion with petroleum ether (60-90 ℃) which is 3 times of the volume of the dispersion, ethyl acetate and n-butanol, extracting each solvent for 5 times, respectively merging the extracts of the solvents, concentrating and recovering the solvents, and drying to obtain a petroleum ether part, an ethyl acetate part and an n-butanol part of the total extract extracted by the organic solvent and a water-soluble part remained after the n-butanol extraction; the ethyl acetate fraction and the n-butanol fraction were collected and mixed to obtain 65.05g of an extract.
Example 4
The embodiment of the invention provides a periplaneta americana intestinal flora metabolite extract, which is prepared by the following steps: the periplaneta americana faeces is taken as a raw material, crushed and sieved by a 20-mesh sieve to obtain the periplaneta americana faeces coarse powder. Weighing 1kg of periplaneta americana fecal coarse powder, adding 10L of 35% (v/v) ethanol water solution, carrying out reflux extraction for 3 times, extracting for 1 hour each time, filtering, combining filtrate, and recovering ethanol under reduced pressure at 55 ℃ to obtain extract; adding 8 times of water into the obtained extract according to the mass ratio (m/m), stirring and dispersing uniformly, dispersing the dispersion, sequentially extracting the dispersion with petroleum ether (60-90 ℃) 2 times of the volume of the dispersion, ethyl acetate and n-butanol, extracting each solvent for 4 times, respectively merging the extracts of the solvents, concentrating and recovering the solvents, and drying to obtain petroleum ether part, ethyl acetate part and n-butanol part of the total extract extracted by the organic solvent and the water-soluble part remained after the n-butanol extraction; the ethyl acetate fraction and the n-butanol fraction were collected and mixed to obtain 73.56g of an extract.
Example 5
The embodiment of the invention provides a periplaneta americana intestinal flora metabolite extract, which is prepared by the following steps: the periplaneta americana faeces is taken as a raw material, crushed and sieved by a 20-mesh sieve to obtain the periplaneta americana faeces coarse powder. Weighing 1kg of periplaneta americana fecal coarse powder, adding 20L of 70% (v/v) ethanol water solution, carrying out reflux extraction for 1 time and 3 hours, filtering, combining filtrate, and recovering ethanol under reduced pressure at 70 ℃ to obtain extract; adding 7 times of water into the obtained extract according to the mass ratio (m/m), stirring and dispersing uniformly, dispersing the mixture, sequentially extracting the dispersion with petroleum ether (60-90 ℃) of 2.5 times of the volume of the dispersion, ethyl acetate and n-butanol, extracting each solvent for 5 times, respectively merging the extracts of the solvents, concentrating and recovering the solvents, and drying to obtain a petroleum ether part, an ethyl acetate part and an n-butanol part of the total extract extracted by the organic solvent and a water-soluble part remained after the n-butanol extraction; the ethyl acetate fraction and the n-butanol fraction were collected and mixed to obtain 58.85g of an extract.
Example 6
The embodiment of the invention provides a periplaneta americana intestinal flora metabolite extract, which is prepared by the following steps: the periplaneta americana faeces is taken as a raw material, crushed and sieved by a 20-mesh sieve to obtain the periplaneta americana faeces coarse powder. Weighing 1kg of periplaneta americana fecal coarse powder, adding 15L of 80% (v/v) ethanol water solution, carrying out reflux extraction for 3 times, extracting for 1 hour each time, filtering, combining filtrate, and recovering ethanol under reduced pressure at 65 ℃ to obtain extract; adding 6 times of water into the obtained extract according to the mass ratio (m/m), stirring and dispersing uniformly, dispersing the dispersion, sequentially extracting the dispersion with petroleum ether (60-90 ℃) 2 times of the volume of the dispersion, ethyl acetate and n-butanol, extracting each solvent for 3 times, respectively merging the extracts of the solvents, concentrating and recovering the solvents, and drying to obtain a petroleum ether part, an ethyl acetate part and an n-butanol part of the total extract extracted by the organic solvent and a water-soluble part remained after the n-butanol extraction; the ethyl acetate fraction and the n-butanol fraction were collected and mixed to obtain 60.37g of an extract.
Example 7
The embodiment of the invention provides an application of a periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory and anti-ulcer medicines.
The preparation method comprises the following steps: pulverizing the American cockroach intestinal flora metabolite extract obtained in the example 1, uniformly mixing with microcrystalline cellulose, PVP, sodium carboxymethylcellulose and magnesium stearate, and tabletting to obtain tablets.
Example 8
The embodiment of the invention provides an application of a periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory and anti-ulcer medicines.
The preparation method comprises the following steps: pulverizing the American cockroach intestinal flora metabolite extract obtained in the example 2, adding fumed silica and a flavoring agent, uniformly mixing, and subpackaging to obtain powder.
Example 9
The embodiment of the invention provides an application of a periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory and anti-ulcer medicines.
The preparation method comprises the following steps: mixing the American cockroach intestinal flora metabolite extract obtained in the example 3 with auxiliary materials such as thickening agent, flavoring agent, antioxidant and the like, sterilizing, and packaging to prepare the oral liquid.
Example 10
The embodiment of the invention provides an application of a periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory and anti-ulcer medicines.
The preparation method comprises the following steps: pulverizing the American cockroach intestinal flora metabolite extract obtained in the example 4, mixing with dextrin and starch slurry, granulating, adding talcum powder after finishing, mixing, and filling a 4# hard capsule shell to obtain the hard capsule.
Example 11
The embodiment of the invention provides an application of a periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory and anti-ulcer medicines.
The preparation method comprises the following steps: pulverizing the American cockroach intestinal flora metabolite extract obtained in the example 5, mixing with soybean oil, fully dispersing, sealing in a soft capsule material, and preparing into soft capsules.
Example 12
The embodiment of the invention provides an application of a periplaneta americana intestinal flora metabolite extract in preparing anti-inflammatory and anti-ulcer medicines.
The preparation method comprises the following steps: granulating the American cockroach intestinal flora metabolite extract obtained in the example 6 with microcrystalline cellulose, sugar powder and water, adding magnesium stearate after finishing, mixing, subpackaging and preparing granules.
Comparative example 1
The comparative example provides a periplaneta americana extract, the preparation method of which is based on the example 3, takes periplaneta americana as a raw material, and only carries out ethanol extraction, and the specific operation is as follows: the periplaneta americana coarse powder is obtained by taking periplaneta americana as a raw material, crushing and sieving with a 20-mesh sieve. Weighing 1kg of periplaneta americana coarse powder, adding 12L of 50% (v/v) ethanol, reflux-extracting for 3 times, extracting for 2 hours each time, filtering, mixing filtrates, and recovering ethanol under reduced pressure at 65 ℃ to obtain extract.
Comparative example 2
The comparative example provides a periplaneta americana intestinal flora metabolite extract, the preparation method is based on the example 3, only ethanol extraction is carried out, and the specific operation is as follows: the periplaneta americana faeces is taken as a raw material, crushed and sieved by a 20-mesh sieve to obtain the periplaneta americana faeces coarse powder. Weighing 1kg of periplaneta americana fecal coarse powder, adding 12L of 50% (v/v) ethanol, reflux-extracting for 3 times, extracting for 2 hours each time, filtering, mixing filtrates, and recovering ethanol under reduced pressure at 65deg.C to obtain extract.
Comparative example 3
This comparative example provides an extract of the metabolites of the intestinal flora of periplaneta americana, prepared in the same way as example 3, with only the ethyl acetate fraction.
Comparative example 4
This comparative example provides an extract of the metabolites of the intestinal flora of periplaneta americana, prepared in the same manner as in example 3, with only the n-butanol fraction.
Effect example 1
The effect example provides a pharmacodynamics experiment of the periplaneta americana intestinal flora metabolite extract to acute gastric ulcer model mice.
1. Experimental sample
The extract obtained in example 3 of the present invention; the extracts obtained in comparative examples 1 to 4.
2. Experimental method
2.1 animal model building and group administration
70 clean male Kunming mice, with a weight of 20+ -2 g, are provided by the Chinese medical science academy of hematopathy Hospital, and after one week of adaptive feeding, are randomly divided into 7 groups of 10 mice each, respectively: the sample, comparative example 1, comparative example 2, comparative example 3, comparative example 4, model, and blank groups of example 3 of the present invention were each given by gastric administration for 1 week (the doses of each group were the same, and were all 100 mg/kg), and the blank and model groups were given an equal volume of 0.5wt% CMC-Na solution. Mice were fasted for 24h before the end of the experiment, and after 1.5h of last gastric lavage administration, absolute ethanol (0.2 mL each) was injected by a gastric lavage method to create an acute gastric ulcer model, and normal groups were given the same dose of normal saline for gastric lavage. After 1h of forbidden food, the animal is sacrificed. And measuring corresponding pharmacodynamic indexes.
2.2 detection of gastric ulcer related indicators
The gastric tissue of each group of mice was taken, the length and width of the gastric congestion or diffuse bleeding strips were measured by vernier calipers, the ulcer area was calculated, and the ulcer inhibition rate was calculated.
2.3 statistical methods
The test data are statistically analyzed by SPSS22.0 statistical software, and the statistical data are obtained by mean value +/-standard deviationRepresentation ofThe comparison between groups uses one-way analysis of variance.
3. Experimental results
The area of ulcers and the rate of inhibition of ulcers in each group of mice are shown in Table 1.
Note that: in comparison with the set of models, * P<0.05, ** P<0.01。
the results in table 1 show that in the treatment of mice with acute gastric ulcer model, each group of samples has better treatment effect, and compared with the model group, the ulcer areas are smaller to a certain extent, and all the samples show significant differences (P <0.05 or 0.01); among the samples, the samples of the present invention showed the most remarkable anti-ulcer effect, the minimum ulcer area was 58.52% in each group, and the inhibition rate was significantly better than that of the other groups.
Effect example 2
The effect example provides a pharmacodynamics experiment of mice auricle swelling caused by paraxylene extracted from the periplaneta americana intestinal flora metabolite.
1. Experimental sample
The extract obtained in example 3 of the present invention; the extracts obtained in comparative examples 1 to 4.
2. Experimental method
2.1 animal model building and group administration
60 clean male Kunming mice, with a weight of 20+ -2 g, are provided by the Chinese medical science academy of hematopathy Hospital, and after one week of adaptive feeding, are randomly divided into 6 groups of 10 mice each, respectively: the sample, comparative example 1, comparative example 2, comparative example 3, comparative example 4, and model groups of example 3 of the present invention were each given by gastric administration for 1 week (the administration dose of each group was the same, and was 100 mg/kg), and the blank group was given an equal volume of 0.5% CMC-Na solution. Mice were fasted for 24h before the end of the experiment, and after 1h of last gastric administration, xylene was applied to both front and back of the right ear of the mice, 0.1ml per mouse, left ear as control. After 1h, animals are sacrificed, round lugs are respectively punched at the same parts of two lugs by using an 8mm diameter puncher, and the mass is weighed by using an electronic balance. The left and right ear weight difference and the swelling inhibition were calculated.
2.2 statistical methods
The test data are statistically analyzed by SPSS22.0 statistical software, and the statistical data are obtained by mean value +/-standard deviationThe comparison between groups is shown by one-way analysis of variance.
3. Experimental results
The ear weight differences and swelling inhibition rates of the mice in each group are shown in Table 2.
Note that: in comparison with the set of models, * P<0.05, ** P<0.01。
the results in table 2 show that in the acute inflammation model experiment of the auricle swelling of the mice caused by the xylene, each group of samples except the group of comparative example 4 has better treatment effect, and compared with the model group, the difference value of the ear weight is obviously reduced, and the difference value is obvious (P <0.05 or 0.01); among the samples, the anti-inflammatory effect of the samples of the present invention was most remarkable, the difference in the ear weight was the smallest among the groups, the inflammation inhibition rate was 55.69%, and it was remarkably superior to the other groups.
The extract of the invention has obvious anti-inflammatory and anti-ulcer effects by combining the pharmacodynamic experimental results. According to the invention, the ethyl acetate part and the n-butanol part in the alcohol extract are mixed for use, so that the anti-inflammatory and anti-ulcer effects are obviously improved, the synergistic effect is obvious, and the medicinal effect is superior to that of the American cockroach body extract.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, or alternatives falling within the spirit and principles of the invention.
Claims (10)
1. A preparation method of a periplaneta americana intestinal flora metabolite extract is characterized by comprising the following steps: reflux extracting periplaneta americana feces with 20-90% (v/v) ethanol water solution, filtering, preparing the obtained filtrate into extract, and dispersing in water to prepare dispersion liquid; extracting the dispersion liquid with petroleum ether, ethyl acetate and n-butanol in sequence, and collecting ethyl acetate extract and n-butanol extract.
2. The method for preparing the periplaneta americana intestinal flora metabolite extract according to claim 1, which is characterized in that: the reflux extraction is carried out for 1 to 3 times, and each time is 1 to 3 hours.
3. The method for preparing the periplaneta americana intestinal flora metabolite extract according to claim 1, which is characterized in that: the preparation method of the extract comprises the following steps: concentrating under reduced pressure at 55-75deg.C to obtain the extract.
4. The method for preparing the periplaneta americana intestinal flora metabolite extract according to claim 1, which is characterized in that: the petroleum ether is petroleum ether at 60-90 ℃.
5. The method for preparing the periplaneta americana intestinal flora metabolite extract according to claim 1, which is characterized in that: the extraction is to extract with petroleum ether, ethyl acetate and n-butanol for 3-5 times respectively, and the extracts of each solvent are combined.
6. The method for preparing the periplaneta americana intestinal flora metabolite extract according to claim 1, which is characterized in that: the mass of the water is 3-10 times of the mass of the extract; and/or
The volumes of petroleum ether, ethyl acetate and n-butanol are respectively 1-3 times of the volume of water.
7. The method for preparing the periplaneta americana intestinal flora metabolite extract according to any one of claims 1 to 6, which is characterized in that: the preparation method also comprises concentrating and drying the ethyl acetate extract and the n-butanol extract.
8. A periplaneta americana intestinal flora metabolite extract characterized in that it is prepared by the method of preparing the periplaneta americana intestinal flora metabolite extract according to any one of claims 1-7.
9. Use of the periplaneta americana intestinal flora metabolite extract of claim 8 for the preparation of an anti-inflammatory, anti-ulcer product.
10. Use according to claim 9, said product being a pharmaceutical product.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010640421.6A CN111714521B (en) | 2020-07-06 | 2020-07-06 | Periplaneta americana intestinal flora metabolite extract, preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010640421.6A CN111714521B (en) | 2020-07-06 | 2020-07-06 | Periplaneta americana intestinal flora metabolite extract, preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111714521A CN111714521A (en) | 2020-09-29 |
CN111714521B true CN111714521B (en) | 2023-04-28 |
Family
ID=72572150
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010640421.6A Active CN111714521B (en) | 2020-07-06 | 2020-07-06 | Periplaneta americana intestinal flora metabolite extract, preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111714521B (en) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012094834A1 (en) * | 2011-01-14 | 2012-07-19 | 广东药学院 | Compound traditional chinese medicine extract for prevention and treatment of glycometabolism disorders and preparation method thereof |
CN102885855A (en) * | 2012-11-10 | 2013-01-23 | 昆明赛诺制药有限公司 | Production method for preparing medicine for treating peptic ulcer by periplaneta americana extract |
CN104940239A (en) * | 2014-03-27 | 2015-09-30 | 成都百草和济科技有限公司 | Cockroach extract, and preparation method and use thereof |
CN109700830A (en) * | 2019-02-15 | 2019-05-03 | 昆明赛诺制药股份有限公司 | A kind for the treatment of gastritis and the drug of peptic ulcer in good taste and preparation method thereof |
CN110755456A (en) * | 2019-11-29 | 2020-02-07 | 云南中医药大学 | Antifungal medicine composition consisting of American cockroach extract and antifungal medicine |
CN111249311A (en) * | 2020-01-19 | 2020-06-09 | 天津中医药大学 | Extract of metabolic products of intestinal flora in periplaneta americana feces as well as preparation method and application of extract |
-
2020
- 2020-07-06 CN CN202010640421.6A patent/CN111714521B/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012094834A1 (en) * | 2011-01-14 | 2012-07-19 | 广东药学院 | Compound traditional chinese medicine extract for prevention and treatment of glycometabolism disorders and preparation method thereof |
CN102885855A (en) * | 2012-11-10 | 2013-01-23 | 昆明赛诺制药有限公司 | Production method for preparing medicine for treating peptic ulcer by periplaneta americana extract |
CN104940239A (en) * | 2014-03-27 | 2015-09-30 | 成都百草和济科技有限公司 | Cockroach extract, and preparation method and use thereof |
CN109700830A (en) * | 2019-02-15 | 2019-05-03 | 昆明赛诺制药股份有限公司 | A kind for the treatment of gastritis and the drug of peptic ulcer in good taste and preparation method thereof |
CN110755456A (en) * | 2019-11-29 | 2020-02-07 | 云南中医药大学 | Antifungal medicine composition consisting of American cockroach extract and antifungal medicine |
CN111249311A (en) * | 2020-01-19 | 2020-06-09 | 天津中医药大学 | Extract of metabolic products of intestinal flora in periplaneta americana feces as well as preparation method and application of extract |
Non-Patent Citations (4)
Title |
---|
山橿治疗胃溃疡及镇痛抗炎有效部位的筛选;张涛等;《中医学报》;20110501(第05期);597-599 * |
洋虫抗消化性溃疡的活性筛选;曹东等;《中国民族医药杂志》;20081015(第10期);54-57 * |
美洲大蠊不同提取物及不同提取方法对肿瘤细胞的细胞毒性作用;余昕等;《中国实验方剂学杂志》;20160805(第15期);摘要、第154页第2.1.2、2.1.4节 * |
美洲大蠊提取物对乙醇致小鼠急性胃溃疡的预防作用;邹俊波等;《中成药》;20161120(第11期);摘要 * |
Also Published As
Publication number | Publication date |
---|---|
CN111714521A (en) | 2020-09-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100497396C (en) | Dendrobium candidum polysaccharide extractive, medicine composition thereof and its preparation and use | |
CN1621041A (en) | Pharmaceutical composition with pain easing function | |
CN101732668B (en) | Preparation method of Chinese medicinal composition for treating urinary system infection | |
CN1970032B (en) | Chinese medicine containing honeysuckle flower and weeping forsythia for treating cold | |
CN1806821A (en) | Rhinitis-treating medicine | |
CN1250277C (en) | Medicine with antiphlogistic, analgetic, microbiostatic and diuretic effects | |
CN101843659A (en) | Traditional Chinese medicine granular formulation for preventing and treating influenza and preparation method thereof | |
CN102228547B (en) | Application of traditional Chinese medicine composition in preparing medicaments treating pancreatitis and/or cholecystitis | |
CN111714521B (en) | Periplaneta americana intestinal flora metabolite extract, preparation method thereof and application thereof in preparing anti-inflammatory or anti-ulcer products | |
CN102940750B (en) | Medicine composition for treating gout | |
CN101073625B (en) | Medicinal composition with anti-infective and anti-inflammatory functions | |
CN101474258B (en) | Ficus microcarpa var.pusillifolia extract, extracting method and application of the extract | |
CN102940747B (en) | Medicine composition for treating gout | |
CN1264554C (en) | Chinese drug composition for treating viral infection of upper respiratory tract and preparing process thereof | |
CN107865932B (en) | Traditional Chinese medicine composition with weight losing effect | |
CN1824099A (en) | Diffusing-freeing lung rectifying medicinal preparation and its new preparation method | |
CN1282479C (en) | Slowly-released traditional Chinese medicine adhering tablet for treating mouth mucous diseases and its prepn. method | |
CN115364179B (en) | Traditional Chinese medicine composition for reducing blood uric acid as well as preparation method and application thereof | |
CN103316103A (en) | Coccidian-expelling and dysentery-stopping mixture for livestock and preparation method thereof | |
CN114470114B (en) | Application of Mailuoshutong preparation in preparation of medicine for treating constipation | |
CN103230568B (en) | Benorilate vitamin B1 particle for children and preparation process thereof | |
AU2021105111A4 (en) | Drug for treating cancer pain, preparation method and use thereof | |
CN109498737B (en) | Pharmaceutical composition for treating metabolic diseases and preparation method and application thereof | |
CN1236788C (en) | Medicine for curing upper respiratory tract infection and preparation method of its granule preparation | |
CN109908120B (en) | Effective component of Dryopteris stenoptera, extraction method and application thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |