Application of albizia chinensis branch extract in preparation of medicine for preventing and treating gastric ulcer

Abstract

The invention belongs to the technical field of medicines, and discloses a preparation method of an albizia chinensis branch extract and application of the albizia chinensis branch extract in preparation of medicines for preventing and treating gastric ulcer. Specifically, the invention relates to a preparation method for preparing the albizia chinensis branch extract by crushing, extracting and purifying albizia chinensis branches, a pharmaceutical composition containing the albizia chinensis branch extract, and application of the albizia chinensis branch extract in preparation of medicines for preventing and treating gastric ulcer or chronic gastritis diseases caused by various factors such as ethanol.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and relates to an Albizia chinensis (Osbeck) Merr. branch extract and a preparation method thereof. The invention also relates to the medical use of the Albizia chinensis (Osbeck) Merr. branch extract (YSZ) in the preparation of a substance for treating gastric ulcer. Background Art

[0002] Gastric ulcer is a common disease of the digestive system and is prone to recurrence. With the accelerated pace of modern life, increased mental stress and work pressure, as well as bad eating habits such as alcoholism, the incidence of gastric ulcer is on the rise, endangering people's physical and mental health. At present, the most clinically used anti-ulcer Western medicines are mainly drugs such as ranitidine and omeprazole. Although the recent efficacy of Western medicine is obvious, it has adverse reactions and toxic side effects after taking the medicine. Therefore, people begin to look for and dig out new anti-ulcer drugs with high efficiency and low toxicity from traditional Chinese herbal medicines.

[0003] The yingshu tree Albizia chinensis (Osbeck) Merr. is a plant of the genus Albizia in the Leguminosae family. Its medicinal part is the bark, which contains tannins and has the effects of astringing and stopping diarrhea, astringing and promoting tissue regeneration. It is mainly used to treat enteritis, diarrhea, and dysentery (National Collection of Chinese Herbal Medicines, compiled by the National Collection of Chinese Herbal Medicines Compilation Group, second edition, volume 2, 1986, PP768). It is also recorded that the bark of the yingshu tree contains triterpenoid saponins (also known as oxytocin from albizzia), which has the effect of contracting the uterus (Chinese Medicine Dictionary, compiled by Jiangsu New Medical College, 1998, volume 1, PP937).

[0004] In recent years, we have found that Albizia chinensis extract has sedative and hypnotic activity (China Patent Publication No. CN 101766676A), and Albizia bark extract has pharmacological activity in inhibiting proton pump activity and treating gastric ulcer or chronic gastritis (China Patent Publication No. CN 103054932B). So far, there has been no report on the pharmacological activity of Albizia chinensis branch extract in preventing and treating gastric ulcer or chronic gastritis caused by various factors such as alcohol. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a new type of medicine for treating gastric ulcer and chronic gastritis, namely, Albizia chinensis branch extract.

[0006] Another technical problem to be solved by the present invention is to provide a method for preparing the twig extract of Jacaranda chinensis and the twig extract of Jacaranda chinensis obtained by the method.

[0007] Another technical problem to be solved by the present invention is to provide a pharmaceutical composition, comprising an extract of twigs of the Chinese jasmine tree as an active ingredient and a carrier commonly used in the pharmaceutical field.

[0008] Another technical problem to be solved by the present invention is to provide an application of the extract of twigs of the Chinese jasmine tree in the preparation of a medicine for treating gastric ulcer disease.

[0009] In order to solve the technical problem of the present invention, the present invention adopts the following technical scheme:

[0010] The present invention relates to a twig extract of a medicine for treating gastric ulcer disease, and the preparation method thereof is as follows:

[0011] (1) The raw medicinal materials of the Chinese yew tree are crushed and extracted with a solvent, and the extract is concentrated to obtain the Chinese yew tree extract.

[0012] The preferred raw medicinal material of the Chinese yarrow tree is a branch of the Chinese yarrow tree. The raw medicinal material of the Chinese yarrow tree is dried and appropriately crushed to increase the contact area with the solvent and improve the efficiency.

[0013] The extraction solvent of the raw medicinal material can be an alcohol solvent or a mixed solvent of water and alcohol.

[0014] Preferred alcohols include ethanol, methanol, isopropanol, butanol, etc., with ethanol being most preferred.

[0015] The ethanol concentration may be 60-100% by volume; the preferred concentration is 80-95% by volume.

[0016] The volume / weight ratio of the solvent volume to the original medicinal material weight (unit: liter / kg) used during extraction is 4 to 12:1, preferably 8 to 10:1.

[0017] The extraction can be carried out under static or dynamic conditions, preferably under dynamic conditions, such as stirring. In order to improve the efficiency of the extraction, ultrasound or the like can be used.

[0018] The extraction temperature is in the range of room temperature (eg, 20° C.) to the reflux temperature of the solvent, and preferably the reflux temperature of the solvent.

[0019] The extraction can be carried out continuously or intermittently. In the case of intermittent extraction, it can be repeated 1 to 5 times, preferably 3 to 4 times.

[0020] The extraction time is 1-5 hours, preferably 2-3 hours.

[0021] The extracts are combined, heated and concentrated under normal pressure or reduced pressure into a paste, preferably under reduced pressure.

[0022] The preferred preparation method of the Albizia chinensis extract is as follows: weigh the crushed Albizia chinensis branches, reflux with 80-95% ethanol 2-4 times, each time for 2-3 hours; combine the extracts, and concentrate the extracts under reduced pressure to obtain the Albizia chinensis (Osbeck) Merr extract.

[0023] (2) The extract of the elm tree is further separated by polyamide column chromatography and gradient eluted with an alcohol solvent to obtain the elm tree component A.

[0024] The jacaranda extract is dissolved in 10-30% ethanol, preferably 20% ethanol.

[0025] The amount of the polyamide adsorbent used is 25 to 80 times, preferably 35 to 40 times, the weight of the sample.

[0026] The eluent may be a mixed solvent of alcohol and water; preferred alcohol solvents are methanol and ethanol, and the most preferred alcohol solvent is ethanol.

[0027] The amount of the elution solvent used is 3-10 times the volume of the polyamide dry powder, and preferably the amount of the eluent used is 6-7 times the volume of the polyamide dry powder.

[0028] The mixture was eluted with 10-30% ethanol, and the eluate was collected and recovered under reduced pressure to obtain component A of the elixir tree.

[0029] The preferred polyamide column chromatography purification step includes: dissolving the elm tree extract in 20% ethanol, adding it to a 30-60 mesh polyamide column that is 30-40 times the weight of the extract, eluting with 20% ethanol, the amount of elution solvent being 5-7 times the volume of the polyamide dry powder, collecting the 20% ethanol eluate and concentrating it to obtain the elm tree component A.

[0030] (3) The component A of the elm tree is purified again by non-polar macroporous resin column chromatography and gradient eluted with an alcohol solvent to obtain the elm tree branch extract.

[0031] The jacaranda component A is dissolved in 5-20% ethanol, preferably 20% ethanol.

[0032] The non-polar macroporous resin filler is preferably AB-8 or D101 type non-polar macroporous resin.

[0033] The amount of non-polar macroporous resin column adsorbent used (measured in wet apparent density) is 6 to 12 times the weight of component A, preferably 8 to 10 times.

[0034] The eluent may be a mixed solvent of alcohol and water; preferred alcohol solvents are methanol and ethanol, and the most preferred alcohol solvent is ethanol.

[0035] The amount of the elution solvent used is 5-10 times the volume of the macroporous resin (measured in wet apparent density), and preferably the amount of the eluent used is 6-8 times the volume of the macroporous resin.

[0036] 20% ethanol and 80-100% ethanol were used in sequence for gradient elution, and the 80-100% ethanol eluate was recovered under reduced pressure to obtain the twig extract of the Chinese cycad.

[0037] The preferred macroporous resin column chromatography purification step includes: dissolving the elm component A in 10-20% ethanol, adding it to a non-polar macroporous resin column that is 8-10 times the weight of the elm component A, and gradient eluting with 20% ethanol and 80-95% ethanol in sequence, with the amount of elution solvent being 6-8 times the volume of the macroporous resin (measured in wet apparent density), and concentrating the 80-95% ethanol eluate to obtain the elm branch extract.

[0038] The invention relates to a pharmaceutical composition, comprising an extract of twigs of the Chinese cycad extracted by the method of the invention and a pharmaceutically acceptable carrier.

[0039] The present invention also relates to a pharmaceutical composition containing the extract of the present invention as an active ingredient and conventional pharmaceutical excipients or adjuvants. Usually, the pharmaceutical composition of the present invention contains 0.1 to 95% by weight of the extract of the present invention.

[0040] The present invention also provides a pharmaceutical composition, which comprises a pharmaceutically effective dose of the twig extract of the jacaranda tree and / or the jacaranda tree extracted by the method of the present invention as an active ingredient and a pharmaceutically acceptable carrier.

[0041] The pharmaceutical composition of the extract of the present invention can be prepared according to methods well known in the art. When used for this purpose, if necessary, the extract of the present invention can be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants to prepare a suitable application form or dosage form that can be used as a human or veterinary drug.

[0042] The extract of the present invention or the pharmaceutical composition containing it can be administered in a unit dosage form, and the administration route can be enteral or parenteral, such as oral, intravenous, intramuscular, subcutaneous, intraperitoneal, nasal, oral mucosa, eyes, lungs and respiratory tract, skin, vagina, rectum, etc., preferably oral administration.

[0043] The dosage form can be a liquid dosage form, a solid dosage form or a semisolid dosage form. Liquid dosage forms can be solutions (including true solutions and colloidal solutions), emulsions (including o / w types, w / o types and multiple emulsions), suspensions, injections (including water injections, powder injections and infusions), eye drops, nasal drops, lotions and liniments, etc. Solid dosage forms can be tablets (including ordinary tablets, enteric-coated tablets, lozenges, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules (including hard capsules, soft capsules, enteric-coated capsules), granules, powders, micropills, dropping pills, suppositories, films, patches, aerosols (powders), sprays, etc.; semisolid dosage forms can be ointments, gels, pastes, etc.

[0044] The extract of the present invention can be made into common preparations, sustained-release preparations, controlled-release preparations, targeted preparations and various microparticle drug delivery systems.

[0045] In order to prepare the unit dosage form into tablets, various excipients known in the art can be widely used, including diluents, binders, wetting agents, disintegrants, lubricants, and glidants. The diluent may be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; the wetting agent may be water, ethanol, isopropanol, etc.; the binder may be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, acacia gum slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinyl pyrrolidone, polyethylene dipropylene glycol, etc.; the disintegrant may be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and tectonic acid, calcium carbonate, polyoxyethylene sorbitan fatty acid ester, sodium dodecyl sulfate; the lubricant and glidant may be talc, silicon dioxide, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc.

[0046] The tablets can be further made into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or double-layer tablets and multi-layer tablets.

[0047] In order to make the dosing unit into a pill, various carriers known in the art can be widely used. Examples of carriers include diluents and absorbents, such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, polyvinyl pyrrolidone, lauric acid macrogol glyceride, kaolin, talc, etc.; binders, such as gum arabic, yellow gum, gelatin, ethanol, honey, liquid sugar, rice paste or flour paste, etc.; disintegrants, such as agar powder, dry starch, alginate, sodium dodecyl sulfate, methyl cellulose, ethyl cellulose, etc.

[0048] In order to prepare the administration unit as a suppository, various carriers known in the art can be widely used. Examples of carriers include polyethylene glycol, lecithin, cocoa butter, higher alcohols, esters of higher alcohols, gelatin, semi-synthetic glycerides, and the like.

[0049] In order to prepare the dosing unit into a capsule, the active ingredient extract of the present invention is mixed with the above-mentioned various carriers, and the resulting mixture is placed in a hard gelatin capsule or a soft capsule. The active ingredient extract of the present invention can also be prepared into a microcapsule, suspended in an aqueous medium to form a suspension, or can be loaded into a hard capsule or prepared as an injection for use.

[0050] For example, the extract of the present invention is made into an injection preparation, such as a solution, a suspension solution, an emulsion, or a freeze-dried powder injection. This preparation can be aqueous or non-aqueous, and can contain one and / or more pharmacodynamically acceptable carriers, diluents, adhesives, lubricants, preservatives, surfactants, or dispersants. For example, the diluent can be selected from water, ethanol, polyethylene glycol, 1,3-propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene isostearyl alcohol, polyoxyethylene sorbitol fatty acid esters, etc. In addition, in order to prepare an isotonic injection, an appropriate amount of sodium chloride, glucose, or glycerol can be added to the injection preparation. In addition, conventional cosolvents, buffers, pH regulators, etc. can also be added. These adjuvants are commonly used in the art.

[0051] In addition, if necessary, colorants, preservatives, perfumes, flavoring agents, sweeteners or other materials may be added to the pharmaceutical preparations.

[0052] In order to achieve the purpose of medication and enhance the therapeutic effect, the drug or pharmaceutical composition of the present invention can be administered by any known administration method.

[0053] The dosage of the extract pharmaceutical composition of the present invention depends on many factors, such as the nature and severity of the disease to be prevented or treated, the sex, age, weight, personality and individual response of the patient or animal, the route of administration, the number of administrations, and the purpose of treatment. Therefore, the therapeutic dose of the present invention can vary widely. Generally speaking, the dosage of the pharmaceutical ingredients in the present invention is well known to those skilled in the art. It can be appropriately adjusted according to the actual amount of the drug contained in the final preparation of the extract composition of the present invention to achieve the requirements of its therapeutically effective amount and complete the prevention or treatment purpose of the present invention. The daily suitable dosage range of the extract of the present invention The dosage of the extract of the present invention is 0.001-150 mg / Kg body weight, preferably 0.1-100 mg / Kg body weight, more preferably 1-60 mg / Kg body weight, and most preferably 2-50 mg / Kg body weight. The above dosage can be administered in a single dosage form or divided into several, such as two, three or four dosage forms. This is limited by the clinical experience of the doctor administering the drug and the dosage regimen including the use of other treatment methods. The total dose required for each treatment can be divided into multiple doses or administered in one dose. The extract or composition of the present invention can be taken alone, or used in combination with other therapeutic drugs or symptomatic drugs and the dosage can be adjusted.

[0054] The present invention studies the inhibitory effect of the twig extract on ethanol-induced acute gastric ulcer in rats and acetic acid-induced chronic gastric ulcer in rats, proving that the twig extract has significant effects on resisting acute and chronic gastric ulcers and gastritis.

[0055] Beneficial technical effects

[0056] The raw material of the twig extract of the present invention is twig, which is easy to obtain and renewable. The preparation process of the twig extract is simple and suitable for industrial production.

[0057] The invention provides a new natural medicine for the treatment of gastric ulcer and chronic gastritis, and has a particularly good inhibitory effect on gastric ulcer induced by ethanol, which is equivalent to the positive medicine rabeprazole sodium. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1 . Flow chart of preparation of extract of twigs of jacaranda

[0059] Figure 2 .Inhibitory effect of extracts from twigs of Jacaranda on ethanol-induced gastric ulcer in rats

[0060] Figure 3 .Inhibitory effect of extracts from twigs of Jacaranda on acetic acid-induced gastric ulcer in rats DETAILED DESCRIPTION

[0061] The following examples and drug activity experiments are used to further illustrate the present invention. The examples are only for illustration and cannot limit the scope of the present invention.

[0062] Example 1 Preparation method of twig extract of twig of yarrow

[0063] Weigh 2 kg of crude powder of YSZ branches, reflux it with 8 volumes of 95% ethanol for three times, each time for 3 hours; the extract is concentrated under reduced pressure to obtain 107 g of extract, and then dissolved in 20% ethanol. The 20% ethanol-soluble part is added to a 6500 ml polyamide (30-60 mesh) column, eluted with 6L 20% ethanol, and the 20% ethanol eluate is concentrated to dryness to obtain 75 g of YSZ component A. YSZ component A is then separated by a D101 non-polar macroporous resin column, and gradient eluted with 20% ethanol and 95% ethanol in turn. The 95% ethanol eluate is collected and concentrated to obtain 7 g of YSZ branch extract. ( Figure 1 )

[0064] Pharmacological experiments

[0065] Experimental Example 1 Protective effect of YSZ, an extract of jacaranda branches, on ethanol-induced gastric ulcer in rats

[0066] Experimental methods:

[0067] Male rats fasted for 24 hours but not water were randomly divided into 4 groups, including model group, YSZ (25 and 50 mg / kg) group and positive drug rabeprazole sodium group. The model group was gavaged with solvent, and the other groups were gavaged with the corresponding test substance. After 30 minutes, the rats in each group were gavaged with 95% ethanol 5 ml / kg. After 4-6 hours, the animals were killed, the stomach was taken out, and the stomach was flattened and photographed. The images were used to measure the bleeding area of ​​the rat's front stomach using Image J software.

[0068] Experimental results:

[0069] like Figure 2 As shown in the results, the inhibitory rates of 25mg / kg and 50mg / kg doses of YSZ on ethanol-induced gastric ulcer in rats were 89.9% and 98.3% respectively (p<0.001). This indicates that YSZ has a good preventive and therapeutic effect on acute gastric ulcer caused by ethanol, which is comparable to the positive drug rabeprazole sodium. Figure 2 (Ulcer index is expressed as X±SD, n=8. Compared with the model group, *p<0.05, **p<0.01) Experimental Example 2 Therapeutic effect of YSZ, an extract of twigs of Jacaranda, on chronic acetic acid-induced gastric ulcer in rats

[0070] Experimental methods:

[0071] Rats were fasted for 24 hours and anesthetized with sodium pentobarbital. 20 μl of acetic acid was injected into the glandular stomach near the pylorus. The animals were randomly divided into groups on the second day after surgery and began to be medicated once a day for 10 consecutive days. The stomach was removed and fixed 24 hours after the last medication. The stomach was flattened and photographed, and the ulcer area was measured using Image J software.

[0072] Experimental results:

[0073] like Figure 3 As shown in the figure, in the rat model of chronic gastric ulcer induced by acetic acid, the test drug YSZ, a 150 mg / kg extract of yam twigs, reduced the gastric ulcer area of ​​rats by 64% compared with the model group, indicating that the effect of YSZ, a yam twig extract, in promoting the healing of gastric ulcers is obvious. Figure 3 As shown (the ulcer area is expressed as X±SD, n=8. Compared with the model group, ****p<0.0001).

Claims

1. A use of an extract of twigs of the Chinese yam tree for preparing a drug for preventing and treating acute or chronic gastric ulcer disease or chronic gastritis, characterized in that: The preparation method of the twig extract of the Chinese yarrow comprises the following steps: Step A: taking crushed twigs of the Chinese twig, refluxing them with 4-10 liters of 60-100% ethanol per kilogram of medicinal material for 2-4 times, each time for 2-3 hours; combining the extracts, and concentrating the extracts under reduced pressure to obtain a twig extract; Step B: Dissolve the cypress extract obtained in step A in 10-30% ethanol, add it to a 30-90 mesh polyamide column which is 30-40 times the weight of the extract, elute with 10-30% ethanol, the amount of elution solvent is 5-10 times the volume of 30-90 mesh polyamide dry powder, collect the 10-30% ethanol eluate and concentrate to obtain cypress component A. Step C: Dissolve the cypress component A obtained in step B in 20% ethanol, add it to a non-polar macroporous resin column (measured in wet apparent density) which is 10-15 times the weight of component A, elute with 20% and 80-100% ethanol solutions in turn, the amount of elution solvent is 5-8 times the volume of the macroporous resin, collect the 80-100% ethanol eluate and concentrate to obtain the cypress branch extract.

2. A pharmaceutical composition, characterized in that Contains the twig extract of claim 1 as an effective ingredient, and a pharmaceutically acceptable carrier.

3. The use according to claim 1, characterized in that The acute gastric ulcer is an ethanol-induced gastric ulcer.

4. The use according to claim 1, characterized in that The chronic gastric ulcer is gastric ulcer induced by acetic acid.

5. Use of twigs of the Chinese cypress tree in the preparation of medicines for preventing or treating acute or chronic gastric ulcers or chronic gastritis.

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