WO2017020862A1 - Application d'une composition de polygonum capitatum dans le traitement d'une gastrite - Google Patents

Application d'une composition de polygonum capitatum dans le traitement d'une gastrite Download PDF

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WO2017020862A1
WO2017020862A1 PCT/CN2016/093627 CN2016093627W WO2017020862A1 WO 2017020862 A1 WO2017020862 A1 WO 2017020862A1 CN 2016093627 W CN2016093627 W CN 2016093627W WO 2017020862 A1 WO2017020862 A1 WO 2017020862A1
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weight
parts
pharmaceutical composition
composition according
group
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PCT/CN2016/093627
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English (en)
Chinese (zh)
Inventor
王子厚
张声生
周益成
张姝
胡伏莲
朱洁
张丽艳
丁莉梅
莫非
荣祖元
罗昭逊
叶茂华
何云
朱菊红
朱晓龙
郑伟霞
马领弟
任燕君
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浙江众康药业有限公司
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Priority claimed from PCT/CN2015/086157 external-priority patent/WO2017020280A1/fr
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Publication of WO2017020862A1 publication Critical patent/WO2017020862A1/fr

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    • 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)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/718—Coptis (goldthread)

Definitions

  • the invention belongs to the field of traditional Chinese medicine, and particularly relates to a pharmaceutical composition comprising a flower bud and a berberine, and the preparation thereof for anti-inflammatory, common gastritis, anti-ulcer, especially for preventing/treating chronic gastritis caused by Helicobacter pylori, and The use of drugs for diseases associated with Helicobacter pylori infection.
  • the head flower bud is the dry whole grass or aboveground part of the Polygonum capitatum Buch.-Ham.ex D.Don. It is a commonly used medicine in the folk areas of China, especially in the Miao area.
  • the head flower is sweet, spicy and cool; it has the functions of clearing away heat and dampness, detoxification and relieving pain, and blood stasis, diuretic and drenching.
  • pharmacological studies have shown that the head flower bud has a wide range of pharmacological activities, including analgesic, cooling, diuretic, anti-inflammatory, antibacterial and the like.
  • H.pylori H.p or HP in this context
  • HP infection is an important cause of a variety of chronic stomach diseases such as peptic ulcer, gastritis, and gastric cancer.
  • PPI proton pump inhibitor
  • expectorant the eradication rate is 90%.
  • these drug eradication programs have problems of toxic side effects, easy secondary resistance, double infection, and patient dependence.
  • H.pylori is a damp-heat and detoxification, which belongs to the category of "evil gas". It is difficult for a single Chinese medicine to cope with the complex and changeable condition of the disease. The role of the symptoms.
  • the invention is based on the single-flavored medicine of the head flower, and the other Chinese medicine is used to form the head flower bud composition, which improves the anti-Hp activity and has a good antibacterial effect on the gram-resistant bacteria, especially the methicillin-resistant epidermis.
  • Staphylococcus methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus.
  • the addition of heat-clearing and detoxifying, tonic, diuresis, qi, blood circulation, dehumidification, phlegm, blood circulation, warming, dispelling cold, digestion can reduce the adverse reactions of single-flavor drugs.
  • the composition has heat and dampness, spleen and qi.
  • the object of the present invention is to provide a pharmaceutical composition comprising a flower bud, a berberine, and a composition for preparing an effective anti-inflammatory, common gastritis, in particular, an anti-ulcer, prevention/treatment of chronic gastritis caused by Helicobacter pylori, And the use of drugs for diseases associated with H. pylori infection.
  • a first aspect of the present invention provides a pharmaceutical composition, characterized in that the composition comprises a head flower bud and a berberine.
  • Preferred compositions include 10 to 90 parts by weight of the head flower and 1 to 10 parts by weight of the berberine.
  • the composition consists of a head flower bud, a berberine, a tonic drug, a water-wetting drug, and a drug.
  • the present invention also provides a process for the preparation of the above pharmaceutical composition extract.
  • the present invention also discloses formulations containing a pharmaceutical composition which is formulated with a pharmaceutically acceptable excipient into a pharmaceutically acceptable oral formulation.
  • the oral preparation is selected from various available regular release preparations and sustained release preparations.
  • the sustained-release preparation is selected from the group consisting of a skeleton type, a membrane-controlled type, an osmotic pump type, and a gastric retention type sustained-release preparation.
  • the gastric retention type sustained release preparation is preferably a gastric floating agent.
  • the invention also discloses the use of any of the pharmaceutical compositions of the invention for the preparation of an anti-inflammatory drug.
  • the anti-inflammatory is for the prevention/treatment of gastritis.
  • the gastritis is chronic gastritis.
  • the chronic gastritis is caused by Helicobacter pylori.
  • the invention also discloses the use of any of the pharmaceutical compositions of the invention in the manufacture of an anti-ulcer drug.
  • the ulcer includes gastric ulcer, duodenal ulcer, peptic ulcer.
  • the present invention also discloses the use of any of the pharmaceutical compositions of the present invention for the preparation of a medicament for preventing/treating a disease associated with H. pylori infection.
  • the diseases associated with Helicobacter pylori infection include gastric ulcer, duodenal ulcer, peptic ulcer, acute gastritis, superficial gastritis, atrophic gastritis, gastric mucosa-associated lymphoma, gastric cancer, recurrence of peptic ulcer, Gastric mucosal atrophy, intestinal metaplasia, gastrointestinal dysfunction, and their complications.
  • the present invention provides a novel pharmaceutical composition
  • a novel pharmaceutical composition comprising a head flower bud and a berberine.
  • Preferred compositions include 10 to 90 parts by weight of the head flower and 1 to 10 parts by weight of the berberine.
  • the composition consists of a head flower bud, a berberine, a tonic drug, a water-wetting drug, and a qi medicine.
  • the composition comprises 10 to 90 parts by weight of the head flower, 1 to 10 parts by weight of the berberine, 2 to 30 parts by weight of the tonic drug, 3 to 60 parts by weight of the water-wetting drug, and 2 to 20 parts by weight of the drug.
  • the tonic drugs according to the present invention include, but are not limited to, licorice, codonopsis, atractylodes, white peony, jujube, ginseng, tea, astragalus, and huangjing.
  • the water-wetting agent according to the present invention includes, but is not limited to, cockroaches, knotweed, and earthworms.
  • the qi medicines of the present invention include, but are not limited to, dried tangerine peel, woody fragrant, citrus aurantium, fragrant sage, perilla stalk, August stalk, and earthworm mustard.
  • the preferred tonics are selected from the group consisting of Codonopsis, Astragalus, Atractylodes, Radix Paeoniae Alba, and Polygonatum.
  • the preferred water-wetting type is selected from the group consisting of cockroaches, knotweed, and earthworms.
  • the preferred gas is selected from the group consisting of tangerine peel, woody, citrus, and fragrant.
  • compositions of the invention are as follows:
  • compositions are selected from any of the following groups:
  • composition according to the first aspect of the present invention characterized in that the composition is obtained by extracting the head flower buds and other medicinal materials with an inorganic or organic solvent alone or in a mixed solvent.
  • composition according to the first aspect of the present invention characterized in that the composition is obtained by extracting and mixing the head flower buds and other medicinal materials with two or more mixed solvents of water and ethanol, acetone, and ethyl acetate.
  • a pharmaceutical composition according to the first aspect of the present invention characterized in that the composition is obtained by extracting 5-30 times of water from the head flower and other herbs.
  • composition according to the first aspect of the present invention characterized in that the composition is obtained by extracting 5-30 times of a 30-100% organic solution of the head flower buds and other medicinal materials.
  • the pharmaceutical composition according to the first aspect of the present invention characterized in that the composition is extracted from 5-30 times of 30-99% of lower alcohol (C1-C5), acetone, acetic acid solution by head flower buds and other medicinal materials. And get.
  • lower alcohol C1-C5
  • acetone acetic acid solution by head flower buds and other medicinal materials. And get.
  • composition obtained by extracting 5-30 times of a 30-99% aqueous solution of ethanol as an extraction solvent.
  • the aqueous ethanol solution is preferably a 70% ethanol solution, and the solution is selected to be 6-8 times.
  • composition according to the first aspect of the present invention characterized in that the composition is obtained by extracting and mixing 5-15 times of a mixed solution of an alcohol and an ester of 5-95% of an anthraquinone and other medicinal materials.
  • composition according to the first aspect of the present invention characterized in that the composition is obtained by extracting and extracting 5-15 times of a mixed solution of 5-95% ethanol and ethyl acetate as an extraction solvent. .
  • composition according to the first aspect of the present invention characterized in that the composition is obtained by extracting 5 to 20 times of ethyl acetate, petroleum ether and diethyl ether from the head flower and other herbs.
  • composition prepared according to the method comprising the steps of: 5 to 30 times (e.g., 5 to 15 times, for example, 6 to 12) of the medicinal material constituting the composition.
  • water water
  • ethanol ethanol aqueous solution decoction and / or reflux extraction 1 to 5 times (for example, 2 to 3 times)
  • each 0.5 to 5 hours for example, 0.5 to 3 hours, for example, 1 to 3 hours
  • the filtrate was concentrated and dried.
  • composition prepared according to the method comprising the steps of: taking a medicinal material constituting the composition, adding 5 to 30 times (for example, 5 to 15 times, for example, 6 to 12 times) water is decoctioned at 50-100 ° C for 1 to 5 times (for example, 2 to 3 times), 0.5 to 5 hours each time (for example, 0.5 to 3 hours, for example, 1 to 3 hours), filtered and combined
  • the extract is concentrated to a thick paste having a relative density of 1.1 to 1.5 (for example, 1.2 to 1.4), and dried under reduced pressure.
  • composition prepared according to the method comprising the steps of: taking a medicinal material constituting the composition, adding 5 to 30 times (for example, 5 to 15 times, for example, 6 to 12 times) 30 to 99% of B
  • the alcohol aqueous solution is refluxed and extracted 1 to 5 times (for example, 2 to 3 times) for 0.5 to 5 hours (for example, 0.5 to 3 hours, for example, 1 to 3 hours), and the extract is filtered and combined, 60 to 90 ° C (for example, 65 °).
  • the above pharmaceutical composition further comprises one or more other drugs selected from the group consisting of: an antimicrobial agent, a proton pump inhibitor, a gastric mucosal protective agent, an antacid, and an H2 receptor antagonist.
  • Preferred antimicrobial agents include, but are not limited to, penicillins such as amoxicillin, macrolides such as clarithromycin, and nitrazoles such as metronidazole.
  • Preferred proton pump inhibitors include, but are not limited to, omeprazole, lansoprazole, pantoprazole
  • Preferred gastric mucosal protective agents include, but are not limited to, sucralfate, smecta
  • Preferred antacids such as aluminum hydroxide magnesium
  • Preferred H2 receptor antagonists such as cimetidine, ranitidine, famotidine.
  • the invention also discloses a method for preparing a pharmaceutical composition extract, characterized in that the step of the method is selected from any one or more of the following:
  • (1-7) is obtained by extracting and obtaining 5 to 15 times of a mixed solvent of 5 to 95% of an alcohol and an ester;
  • the invention includes all of the pharmaceutical composition extracts prepared by the above methods.
  • a second aspect of the invention provides a pharmaceutical formulation composition.
  • compositions of the present invention further comprise one or more non-toxic physiologically acceptable carriers.
  • the acceptable carriers include any excipients known in the art and excipients that function as controlled release. Commonly used excipients include diluents, binders, wetting agents, disintegrants, lubricants, glidants, porogens, plasticizers, fillers, solubilizers, and emulsifiers.
  • the diluent may be, but not limited to, starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.;
  • the humectant may be but not Limited to water, ethanol, isopropanol, etc.
  • the binder may be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, gum arabic, gelatin pulp, sodium carboxymethyl cellulose, methyl fiber , hydroxypropyl methylcellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.
  • disintegrants can be, but are not limited to, dry starch, microcrystalline cellulose, low substitution Hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, croscarmellose sodium, sodium carboxymethyl star
  • the excipient that acts to slow release is selected from one or more of a hydrophilic gel material, a waxy material, and an insoluble material.
  • the hydrophilic gel material may be selected from the group consisting of hydroxypropylmethylcellulose, carbopol, sodium carboxymethylcellulose and alginate
  • the waxy lipid material may be selected from the group consisting of cetyl alcohol and ten.
  • the insoluble material may be selected from the group consisting of ethyl cellulose, acrylic resin, polyoxyethylene and polyethylene.
  • coloring agents may also be added to the pharmaceutical preparations as needed.
  • the invention also relates to formulations comprising a pharmaceutical composition and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition Any dosage form suitable for human or animal use can be prepared by combining the composition with one or more pharmaceutically acceptable solid or liquid excipients and/or adjuvants.
  • the formulation can be prepared according to methods well known in the art.
  • the composition of the present invention is usually contained in a pharmaceutical preparation in an amount of 6 to 12 g.
  • the pharmaceutical preparation of the present invention is preferably an oral preparation for the purpose of administration and enhancing the therapeutic effect.
  • the oral preparation prepared by the pharmaceutical composition of the present invention comprises a granule, a tablet, a pill, a capsule, an oral liquid preparation and the like, and a sustained release preparation comprising a skeleton type and a film.
  • Controlled, osmotic pump type, gastric retention type sustained release controlled release preparation, microcapsule, nanoparticle, liposome and other drug new carrier sustained release controlled release preparation, gastric retention type controlled release preparation is preferably gastric floating Agent.
  • the preparation process of the preparation is as follows:
  • the raw material was 31% of the composition, 31% of the IV acrylic resin, 31% of stearyl alcohol, 7% of MCC101, and an appropriate amount of magnesium stearate was added, and the film was directly compressed by a dry method to obtain a floating tablet of the first calyx composition.
  • a third aspect of the invention provides the use of a pharmaceutical composition for the preparation of an anti-inflammatory drug.
  • the use according to the third aspect of the present invention is characterized in that the anti-inflammatory is for preventing/treating gastritis.
  • the use according to the third aspect of the invention is characterized in that the gastritis is chronic gastritis.
  • the use according to the third aspect of the present invention is characterized in that the chronic gastritis is caused by H. pylori.
  • a fourth aspect of the invention provides the use of a pharmaceutical composition for the preparation of an anti-ulcer drug.
  • the use according to the fourth aspect of the present invention is characterized in that the ulcer comprises a gastric ulcer, a duodenal ulcer, a peptic ulcer.
  • a fifth aspect of the present invention provides the use of a pharmaceutical composition for the preparation of a medicament for preventing/treating a disease associated with H. pylori infection.
  • the disease associated with H. pylori infection includes gastric ulcer, duodenal ulcer, peptic ulcer, acute gastritis, superficial gastritis, atrophic gastritis, stomach Mucosa-associated lymphoma, gastric cancer, recurrent peptic ulcer, gastric mucosal atrophy, intestinal metaplasia, and their complications.
  • extraction may be impregnation at normal temperature, or extraction at elevated temperatures (e.g., boiling and/or reflux), or a combination of these modes of operation. It may further comprise further processing the extract, such as further purification, such as solvent removal, precipitation removal impurities, solvent extraction, resin adsorption separation, and the like.
  • extract will include extracts of any purity that can be used to achieve any of the objectives of the invention, and the extraction purity of the extract can vary over a wide range.
  • the beneficial effects of the present invention are that the composition also increases the unilateral anti-gastric ulcer activity.
  • the inhibition rate of water-extracting composition B (1.5g/kg) against ethanolic ulcer in rats was 81.1% (p ⁇ 0.01), higher than that of head buds 36.4% (1.5g/kg) and berberine 42.4% (3g/kg).
  • the inhibition rate of water extract composition A (0.75g/kg) against ethanolic ulcer in rats was 74.0% (p ⁇ 0.01); the inhibition rate of water extracting composition A (3g/kg) on reserpine ulcer in mice 64.8% (p ⁇ 0.01), higher than the head flower unilateral 60.4 (6g / kg) and berberine 49.4% (6g / kg).
  • the composition has a good effect on the treatment of chronic gastritis caused by H. pylori.
  • the water extracting compositions A and B (the raw material content of the head flower buddha 526.67 mg/ml, medium dose) were higher than the unilateral (high, medium and low doses) of the head flower buds, and the Hp rate was 95.57% and 97.32%, respectively (P ⁇ 0.05);
  • Water extracting compound B has better curative effect on the inflammation of gastritis than the single dose of the top flower bud; the water extracting compositions B and C are significantly improved compared with omeprazole; the water extracting compositions A, B and C are better than Amo
  • the Xilin group has a good effect.
  • composition composition of the invention has the functions of clearing heat and dampness, spleen and qi. It is used for spleen and stomach qi deficiency, stomach heat pain caused by dampness and heat resistance, phlegm and blood stasis, nausea and vomiting, loss of appetite, etc., while eradicating Hp, regulating gastrointestinal balance, preventing spleen and stomach damage, liver and spleen.
  • Figure 1 shows the gastric mucosal inflammation in SD rats in the experimental group.
  • Example 2 Referring to the same method as in Example 1, except that 750 g of medicinal herbs, 75 g of fried berberine, 250 g of Codonopsis pilosula, 250 g of medlar, and 150 g of dried tangerine peel were weighed, and the extract powder of the present example was obtained, 154 g.
  • Example 2 The same procedure as in Example 1 was carried out, except that 900 g of the medicinal material calyx was weighed and extracted, and 89 g of the extract powder of this example was obtained.
  • Example 2 The same procedure as in Example 1 was carried out, except that 660 g of the medicinal material of Rhizoma Coptidis was weighed, and 133 g of the extract powder of this example was obtained.
  • the method was the same as in the same manner as in Example 5 except that 300 g of medicinal materials, 30 g of fried berberine, 100 g of Codonopsis pilosula, 100 g of medlar, and 60 g of dried tangerine peel were weighed, and the extract powder of this example was obtained, 95 g.
  • Example 5 Referring to the same method as in Example 5, except that 300 g of the medicinal flower head flower, 30 g of fried berberine, 100 g of Codonopsis pilosula, 100 g of medlar, and 100 g of Schisandra were weighed, and the extract powder of this example was obtained, 102 g.
  • Example 5 The same procedure as in Example 5 was carried out except that 520 g of the Rhizoma Coptidis medicinal material was weighed, and the extract powder of this example was obtained, 95 g.
  • Example 2 Referring to the same method as in Example 1, the difference was that 80 kg of head flower buds, 8 kg of fried berberine, and 16 kg of raw licorice were weighed and extracted to obtain 8.1 kg of the extract powder of this example.
  • Example 2 Referring to the same method as in Example 1, the difference was that 54 kg of the flower head flower, 5.6 kg of fried berberine, 17.6 kg of Codonopsis pilosula, 17.6 kg of medlar, and 10.4 kg of dried tangerine peel were weighed, and the extract powder of this example was obtained, 17.0 kg.
  • Example 2 Referring to the same method as in Example 1, the difference was that 48 kg of the flower head flower, 4.8 kg of fried berberine, 16 kg of Codonopsis pilosula, 16 kg of medlar, and 16 kg of Schisandra were weighed, and the extract powder of this example was obtained, 20.0 kg.
  • Example 14 Preparation of fried yellow water extract extract powder
  • Example 2 Referring to the same method as in Example 1, the difference was that 76 kg of the medicinal material was weighed and extracted, and the extract powder of this example was obtained, 3.1 kg.
  • Example 2 The same procedure as in Example 1 was carried out except that 500 g of the head flower buds, 50 g of fried berberine, and 100 g of raw licorice were weighed and extracted to obtain the extract powder of the present example, 64.2 g.
  • Example 2 The same procedure as in Example 1 was carried out except that 300 g of the medicinal material head flower, 30 g of fried berberine, 100 g of Codonopsis pilosula, 100 g of medlar, and 60 g of dried tangerine peel were weighed, and the extract powder of this example was obtained, 78 g.
  • Example 2 The same procedure as in Example 1 was carried out, except that 300 g of the medicinal flower head flower, 30 g of fried berberine, 100 g of Codonopsis pilosula, 100 g of medlar, and 100 g of Schisandra were weighed, and the extract powder of this example was obtained, 85.4 g.
  • Example 2 The same procedure as in Example 1 was carried out, except that 600 g of the medicinal plant head flower was weighed and extracted, and the extract powder of this example was obtained, 50.2 g.
  • Example 2 The same procedure as in Example 1 was carried out except that 300 g of the medicinal material head flower, 30 g of fried berberine, 100 g of Codonopsis pilosula, and 100 g of medlar were weighed, and the extract powder of this example was obtained, 78.8 g.
  • Example 5 The same procedure as in Example 5 was carried out except that 300 g of the medicinal material calyx, 30 g of fried berberine, 100 g of Codonopsis pilosula, and 100 g of medlar were weighed, and the extract powder of this example was obtained, 79 g.
  • Example 2 The same procedure as in Example 1 was carried out except that 300 g of the medicinal material head flower, 30 g of fried berberine, 100 g of medlar, and 60 g of dried tangerine peel were weighed, and the extract powder of this example was obtained, 64 g.
  • Example 5 The same procedure as in Example 5 was carried out except that 300 g of the medicinal material head flower, 30 g of fried berberine, 100 g of medlar, and 60 g of dried tangerine peel were weighed, and the extract powder of this example was obtained, 66 g.
  • Example 2 Referring to the same method as in Example 1, the difference was that 300 g of the medicinal material calyx, 30 g of fried berberine, 100 g of Codonopsis pilosula, and 100 g of Schisandra were weighed, and the extract powder of the present example was obtained, 80 g.
  • Example 5 Referring to the same method as in Example 5, the difference was that 300 g of the medicinal material head flower, 30 g of fried berberine, 100 g of Codonopsis pilosula, and 100 g of schisandra were weighed, and the extract powder of this example was obtained, 84 g.
  • Example 2 The same procedure as in Example 1 was carried out except that 300 g of the medicinal material head flower, 30 g of fried berberine, 100 g of medlar, and 100 g of schisandra were weighed, and the extract powder of this example was obtained, 86 g.
  • Example 5 The same procedure as in Example 5 was carried out except that 300 g of the medicinal material head flower, 30 g of fried berberine, 100 g of medlar, and 100 g of schisandra were weighed, and the extract powder of this example was obtained, 88 g.
  • Test Example 1 Protective effect of composition on reserpine caused by gastric mucosa
  • mice 140 SPF grade KM mice, ⁇ 70, weighing 17 ( ⁇ 1) g, supplied by Chengdu Dashuo Biotechnology Co., Ltd., production license number SCXK (chuan) 2008-24.
  • Ranitidine capsules purchased from Southwest Synthetic Pharmaceutical Co., Ltd.
  • Reserpine injection purchased from Tianjin Jinyao Pharmaceutical Co., Ltd.
  • CMC purchased from Chengdu Kelong Chemical Reagent Factory.
  • the head of the flower water bill of lading is provided by Guiyang Medical College, the batch number is 14196, and the crude drug content is 10.35g/g.
  • Sample solution preparation Prepare a suspension of the desired concentration with 0.5% CMC before use.
  • the quarantine period uses the tail marking method, that is, the animal number is indicated by a marker line at the end of the rat. Prior to administration, they were grouped by stratified randomization grouping method and labeled with picric acid staining.
  • the blank control group and the model control group were given 0.5% mg/ml of CMC, and the first flower bud composition was selected from three dose groups of 3, 6, and 12 g/kg.
  • the positive control group was ranitidine 0.2g/kg, the first flower bud and the berberine single group 6g/kg. Each group of animals was intragastrically administered once a day for 6 days. After the 6th day, the rats were fasted to avoid water. When fasting to 18 hours, except for the blank control group, each group of animals was given subcutaneous injection of reserpine 10 mg. /kg (ie 0.1ml/10g).
  • the animals were sacrificed 6 hours after the injection of reserpine.
  • the whole stomach was removed after ligation of the pylorus and the cardia.
  • 2 ml of 4% formaldehyde solution was injected into the stomach gland, and then immersed in a 4% formaldehyde solution.
  • the gastric cavity was dissected along the large curvature of the stomach, the stomach wall was unfolded, washed with running water, and the number of ulcers in the glandular stomach of each animal was recorded by a magnifying glass or a stereo microscope.
  • Body weight before administration and before anatomy
  • Model control group indicates that P ⁇ 0.05 by inter-group analysis of variance; ** indicates that the model control group was tested by Dunnet multiple comparison test P ⁇ 0.01
  • the three prescriptions of the head flower bud composition showed good curative effect on the reserpine gastric ulcer in mice, and there was a statistically significant difference. Each dose had no significant effect on the body weight of the animal.
  • the high-dose ulcer inhibition rate of the low-dose of the first flower bud composition A and the flower bud composition B and the flower bud composition C exceeded 60% (P ⁇ 0.01).
  • Test Example 2 Protective effect of the first flower bud composition on ethanol-induced gastric mucosa 1
  • mice were randomly divided into 11 groups, 12 rats/group, half male and half female.
  • the blank control group and the model control group were given 0.5% mg/ml CMC
  • the first flower bud composition was selected from two dose groups of 1.5 and 6 g/kg
  • the positive control group was ranitidine 0.1 g/kg
  • the head flower buds single group was 1.5.
  • g/kg Huanglian unilateral group 3g/kg.
  • Each group of animals was intragastrically administered once a day for 6 days. After the 6th day, the rats were fasted to avoid water. When fasting to 47 hours, except for the blank control group, each group of animals had 5 ml/kg of absolute ethanol. (ie 0.5ml/100g).
  • the animals were sacrificed 1 hour after the administration of ethanol, and the whole stomach was taken after ligating the pylorus and the cardia. 5 ml of 4% formaldehyde solution was injected into the stomach gland, and then immersed in a 4% formaldehyde solution. After 30 minutes, the stomach cavity was opened along the large curvature of the stomach, the stomach wall was unfolded, washed with running water, and the flocculation damage on the gastric mucosa was carefully observed. The length was measured with a vernier caliper, and the strip-shaped damage was greater than 1 mm, and the measurement length was measured per mm. Minute. If the strip width is greater than 1 mm, the score is doubled and the total score is taken as the ulcer index.
  • Model control group indicates that P ⁇ 0.05 by inter-group analysis of variance; *, ** indicates that the model control group was tested by Dunnet multiple comparison test P ⁇ 0.05, P ⁇ 0.01
  • Test Example 3 Protective effect of the first flower bud composition on ethanol-induced gastric mucosa 2
  • the model control group was given 0.5% mg/ml CMC
  • the first flower bud composition was selected to be 0.75, 1.5 g/kg in two dose groups
  • the positive control group was ranitidine 0.1 g/kg
  • the first group was 1.5 g/kg.
  • the administration protocol is referred to Test Example 5. The results are shown in Table 6.
  • Model control group indicates that P ⁇ 0.05 by inter-group analysis of variance; *, ** indicates that the model control group was tested by Dunnet multiple comparison test P ⁇ 0.05, P ⁇ 0.01
  • Test Example 4 The treatment of chronic gastritis caused by Helicobacter pylori by the first flower bud composition
  • H.pylori colonization in the gastric mucosa of rats and chronic inflammatory pathological changes in the gastric mucosa were judged as successful modeling.
  • Metronidazole, amoxicillin, clarithromycin, and omeprazole were 10.53 mg/mL, 17.54 mg/mL, 8.77 mg/mL, and 0.35 mg/mL.
  • concentrations of amoxicillin, clarithromycin and omeprazole were 17.54 mg/mL, 8.77 mg/mL and 0.35 mg/mL, respectively.
  • H.pylori eradication According to the rat gastric mucosal urease test, Giemsa staining and bacterial microaerobic culture results, it is determined whether there is H.pylori colonization on the surface of rat gastric mucosa, and all the methods are negative. It was eradicated for H.pylori. If it was not eradicated, the H.pylori clearance ability of rat gastric mucosa was evaluated by the density of H.pylori in rat gastric mucosa. Compared with the model group, the inhibitory effect of H.pylori on gastric mucosa of each group was statistically analyzed.
  • Inflammatory improvement effect According to histopathological changes after HE staining of rat gastric mucosa, microscopic observation of gastric mucosal integrity, glandular arrangement and lamina intestinal infiltration of inflammatory cells, evaluation of model group and treatment group of rat stomach The degree of inflammation development of the mucosa.
  • Measurement data Statistical analysis was performed using SPSS 11.5 software. The T-test (Independent-Sample T test) was used for comparison between the two groups. One-way ANOVA was used for comparison between groups. The variance was not measured by LSD test. Analysis of variance was performed using Dunnett-t, P ⁇ 0.05 was statistically significant.
  • H. pylori infection in SD rats Eight weeks after H. pylori infection in SD rats, the gastric mucosa of rats was taken for bacterial microaerophilic culture. The results showed that the planting density of H. pylori was about 105 cfu/g.
  • HE staining of SD rat gastric mucosa showed no obvious inflammatory changes in the gastric mucosa of the blank group; erosion, lymphocytic infiltration and granuloma necrosis were observed in the gastric mucosa of the model group, and lymphocytes involved the submucosa.
  • the mucosal pathological score showed that the model group score was significantly higher than that of the blank group. There was a statistically significant difference between the two groups (P ⁇ 0.05), suggesting that H. pylori infection in SD rats can cause pathological changes in chronic gastritis.
  • the gastric mucosa Giemsa staining, rapid urease test and bacterial culture test showed that there were a large number of H. pylori colonization in the gastric mucosa of the model group, and the colonization of H. pylori in the gastric mucosa of each group was decreased.
  • the Giemsa staining of the gastric mucosa of the mice in the intervention group showed that there were different numbers of H.pylori in the gastric pits and mucosal surface.
  • the results of bacterial microaerobic culture showed that the density of Hp in the gastric mucosa of the high- and medium-dose mice was higher.
  • the model group was significantly reduced (P ⁇ 0.05) and inhibited more than 90% of bacterial proliferation (Table 7).
  • HE staining showed that compared with the model group, a large number of lymphocytes infiltrated in the gastric mucosa and submucosa of the 11th group, and some of them were small in the form of a small lesion (Fig. 1c). Lymphocytes were scattered (Fig. 1d), and a small amount of scattered lymphocytes were seen in the mucosa and submucosa of the 13th group (Fig. 1e). Examples 12 and 13 improved the HAG.
  • the composition was combined with omeprazole treatment, and the lymphocytes of Example 11 in combination with the omeprazole treatment group were significantly reduced compared to the treatment of the simple composition group (Fig. 1j).
  • the mucosa and submucosa were scattered in lymphocytes (Fig. 1g).
  • the mucosa layer to the muscle layer of the head buds were easy to see lymphocytes, and some lymphocytes were clustered together (Fig. 1h).
  • lymphocytes involved the muscular layer, and the mucosa showed erosion (Fig. 1i). Therefore, compared with the single flower bud, the improvement effect of Example 12 is better than that of the top, middle and low doses.
  • Examples 12 and 13 were significantly better than omeprazole; the groups of Examples 11, 12 and 13 were better than the amoxicillin group; the control layer of the control group showed a small amount of scattered lymphocytes (Fig. 1f); The group was significantly improved compared to the Example 14 group.

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Abstract

L'invention concerne une composition pharmaceutique comprenant des racines de Polygonum capitatum et de coptide, et une application de celle-ci pour préparer un médicament permettant de résister à l'inflammation, en particulier de résister à un ulcère, de prévenir et/ou de traiter la gastrite chronique et la gastrite commune provoqués par Helicobacter pylori et de maladies liées à une infection par Helicobacter pylori.
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CN107890539A (zh) * 2017-08-15 2018-04-10 程玉峰金章 一种治疗胃病的中药
CN113413366A (zh) * 2021-06-30 2021-09-21 宁夏医科大学 一种治疗慢性胃炎的干混悬型口服原位凝胶及其制备方法

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