CN103417786A - Semen arecae prepareta extractive capable of promoting gastrointestinal motility and preparing method thereof - Google Patents
Semen arecae prepareta extractive capable of promoting gastrointestinal motility and preparing method thereof Download PDFInfo
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Abstract
The invention belongs to the field of medicine, and discloses a semen arecae prepareta extractive capable of promoting gastrointestinal motility and a preparing method thereof. The method for preparing the semen arecae prepareta extractive includes the steps of extracting semen arecae prepareta 1-3 times by using 30%-70% ethyl alcohol, wherein each time lasts for 0.5-2h; combining and filtering extracting solutions; obtaining the semen arecae prepareta extractive by concentrating the extracting solutions to be dry. Preparations of the extractive can be obtained by adding proper pharmaceutic adjuvant into the semen arecae prepareta extractive and adopting conventional preparation technologies, and then the oral drug preparations such as tablets, capsules, granules, dripping pills and oral solutions and the injectable drug preparations such as freeze-dried powder and hydro-acupuncture preparations can be obtained. The extractive and the preparations thereof have the significant function of promoting gastrointestinal motility, and as shown in toxicity tests at earlier stages, the emen arecae prepareta extractive is nontoxic and can be prepared into food, health food and drugs.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to Semen Arecae Prepareta extract promoted gastrointestinal peristalsis and preparation method thereof.
Background technology
Gastrointestinal promotes medicine, claims again medicine for stomach dynamic, and being to increase the class medicine that gastrointestinal propulsive effect is wriggled.Clinical treatment of disliking vomiting for gastrointestinal distension, esophageal reflux, gastroparesis, functional dyspepsia and chemicotherapy patient.Clinical practice at present is mainly to take chemical medicine as main, and the medicine for stomach dynamic in first, second and third generation commonly used has:
1, stomach oxygen Emetisan.As metoclopramide, paspertin metoclopramide, vomit that sense is flat, Metoclopramide.This is first generation medicine for stomach dynamic, and clinical practice history at most, is come out nearly 40 years so far from the sixties in 20th century, determined curative effect.But disagreeable is that life-time service is prone to the extrapyramidal symptoms, i.e. performance has amyostasia, lower limb muscles tic, torticollis etc., and the untoward reaction such as dizziness, drowsiness, lactogenic also can be arranged.Other also has constipation, diarrhoea, erythra, galactorrhea, gynaecomastia etc., but more rare, drug withdrawal disappears.Anemia of pregnant woman, women breast-feeding their children, children's, old people should be cautious use of.
2, domperidone (Domperidone, Domperidone, domperidone): be second filial generation medicine for stomach dynamic.China went into operation in 1997, had now become domestic topmost medicine for stomach dynamic, acted on stronger.This product easily absorbs, and oral, intramuscular injection, intravenous drip or rectally all can.The clinical gastroparesis caused for a variety of causes, functional dyspepsia, gastroesophageal reflux, nausea and vomiting etc.But to postoperative or due to anesthesia or the vomiting that causes of chemotherapy invalid.Anemia of pregnant woman and baby below 1 years old are cautious use of.Side effect has xerostomia, diarrhoea, erythra.
3, mosapride: be novel third generation medicine for stomach dynamic, be mainly used in treating the esophageal reflux disease, use after chronic gastritis and operation.Can strengthen gastrointestinal motility, but not affect gastric acid secretion.It without the side effect such as extrapyramidal system and reaction and diarrhoea, better tolerance, is its advantage.
Chinese medicine is the rarity of the Chinese nation, is the treasure that the Chinese nation accumulates in the process combated the disease for a long time.We fully use modern science and technology on the basis of development based on inheritance Advantages of TCM characteristic, promote Chinese medicine modernization and internationalization, and to meet the growing requirements of health care of era development and the people, this is the responsibility that history is given us.
The dry mature seed that Semen Arecae is babassu Semen Arecae Areca catechu L..Its effect anthelmintic; Removing food stagnancy; The therapeutic method to keep the adverse QI flowing downwards; Row water; Preventing the attack (or recurrence) of malaria.Malnutrition due to parasitic infestation; Dyspepsia; Abdominal distention; Heavy after dysentery; Foot gas; Edema; Malaria.Semen Arecae is containing total alkaloids 0.3%-0.6%, be mainly arecoline (arecoline), and a small amount of arecaidine (arecaidin), (guvacoline) guvacolines, demethyl arecaidine (guvacine), different demethyl arecaidine (isoguvacine), arecolidine (arecolidine), homarecoline (homoarecoline) etc., all exist with tannic acid (tannic acid) combining form.Also containing tannin approximately 15%, dextrorotation cachou extract (catechin) is inside arranged, left-handed epicatechin (epicatechin), former cyanidin (procyanidin) A-1, B-1 and B-2 and two series compounds that are called Semen Arecae tannin (arecatannin) A, B, dimer, trimer, the tetramer, pentamer that these two series are all former cyanidin.Again fatty approximately 14%, in base, main fatty acid has lauric acid (lauric acid), myristic acid (myristic acid), Palmic acid (palmitic acid), stearic acid (stearic acid), two (2-ethylhexanol) esters [bis (2-ethylhexyl) phthalate] of oleic acid (oleic acid) and a small amount of modern phthalic acid etc.Also containing aminoacid, mainly containing proline (proline) accounts for more than 15%, and tryptophan (TCMLIByptophane), methionine (methionine), cruel propylhomoserin (tyrosine), arginine (arginine), phenylalanine (phenylalanine) etc.Another containing mannose (mannose), galactose (galactose), sucrose (sucrose), areca red (areca red) and Saponin etc.The Preparation process product that Semen Arecae Prepareta is Semen Arecae.
The medication of Semen Arecae tradition is water boiling and extraction, and bibliographical information or existing patent report are that high concentration alcohol extraction or different organic solvents are extracted, and this main pharmacodynamics composition with the promotion gastrointestinal smooth muscle of reporting at present is that biological alkali components is relevant.
The present invention finds by research, the material base that Semen Arecae promotes gastrointestinal smooth muscle to shrink not is entirely the alkaloids composition, the invention provides a kind of Semen Arecae Prepareta extract and preparation thereof, function with significant promotion gastrointestinal peristalsis, and toxic and side effects is little, for developing a kind of new Chinese medicine that strengthens gastric motility, lay a good foundation.
Summary of the invention
Technical problem solved by the invention is to provide a kind of Semen Arecae Prepareta extract that promotes gastrointestinal peristalsis and preparation method thereof, and Semen Arecae Prepareta extract of the present invention can be prepared as follows:
Scheme one: Semen Arecae Prepareta adopts 30%～70% ethanol extraction 1～3 time, and each 0.5～2 hour, merge extractive liquid,, filtered, and filtrate is concentrated into dry, obtains.
Scheme two: the Semen Arecae Prepareta extract adopts following method to make: Semen Arecae Prepareta adopts 6～16 times of amounts of 30%～70% ethanol to extract 1～3 time, and each 0.5～2 hour, merge extractive liquid,, filtered, and filtrate is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.
Wherein, the preferred 40%～60%v/v of concentration of alcohol.
Bibliographical information, Semen Arecae promotes that the main pharmacodynamics composition of gastrointestinal peristalsis is the alkaloids composition, is mainly arecoline and arecaidine.The present invention finds by experimental study: 1, Semen Arecae promotes that the main pharmacodynamics composition of gastrointestinal peristalsis is not only the alkaloids such as arecoline, arecaidine, demethyl arecaidine, because, in the living product of Semen Arecae, alkaloid is high than Semen Arecae Prepareta, but promotes that the drug action Semen Arecae Prepareta of gastrointestinal peristalsis is stronger than raw areca.Therefore, the present invention there is no and takes total alkaloids or arecoline or receive the cream rate in Study on extraction is evaluation index, but directly takes the pharmacodynamics test evaluation index.
The present invention, by the toxicity of postgraduate's Semen Arecae, Semen Arecae Prepareta, finds that Semen Arecae Prepareta toxicity is little, and safety is good, substantially belongs to nontoxic level, the adverse consequences that can avoid the toxicity of raw areca to bring.
In order to utilize the Semen Arecae Prepareta extract, the Semen Arecae Prepareta extract can be added to common medicinal supplementary material, preparation process is made oral formulations or ejection preparation routinely.Oral formulations can adopt the common dosage forms such as tablet, capsule, granule, drop pill or oral liquid.Ejection preparation can adopt the dosage forms such as freeze-dried powder or liquid drugs injection.
The invention has the beneficial effects as follows:
1, Semen Arecae Prepareta extract provided by the invention is a kind of safe and effective extract that can significantly promote gastrointestinal peristalsis.
2, according to the experimental result of this Semen Arecae Prepareta extract, can be developed into food, health food or medicine, particularly be developed to health food or new medicine, can fill up the blank of current Chinese patent medicine gastro-kinetic agent, due to its good safety and effectiveness, for the patient provides a kind of new selection, be conducive to patient body health.
The specific embodiment
Semen Arecae Prepareta extract of the present invention can adopt following two kinds of methods preparation:
One is: Semen Arecae Prepareta adopts 30%～70% ethanol extraction 1～3 time, and each 0.5～2 hour, merge extractive liquid,, filtered, and filtrate is concentrated into dry, obtains.Concentration of alcohol is 40%～60%v/v preferably.
It two is: Semen Arecae Prepareta adopts 6～16 times of amounts of 30%～70% ethanol to extract 1～3 time, and each 0.5～2 hour, merge extractive liquid,, filtered, and filtrate is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.Concentration of alcohol is 40%～60%v/v preferably.
Below by specific description of embodiments of the present invention the explanation but do not limit the present invention.
One, Semen Arecae, Semen Arecae Prepareta medical material assay
According to " content assaying method under Semen Arecae item of Chinese pharmacopoeia version in 2010 carries out assay to Semen Arecae, Semen Arecae Prepareta medical material.
[assay]
Chromatographic condition and system suitability be take the strong cation exchange bonded silica gel as filler (SCX-strong cation-exchanging resin post); Mobile phase: acetonitrile-phosphoric acid solution (2 → 1000, strong ammonia solution condition pH value to 3.8) volume ratio is 55:45; The detection wavelength is 215nm.Theoretical cam curve is calculated and should be not less than 3000 by the arecoline peak.
It is appropriate that Arecoline hydrobromide is got in the preparation of reference substance solution, accurately weighed, adds mobile phase and make the solution of every 1ml containing 0.1mg, obtains (arecoline weight=hydrosulphuric acid arecoline weight/1.5214).
The about 0.3g of this product powder (crossing sieve No. five) is got in the preparation of need testing solution, accurately weighed, put in tool plug conical flask, 50ml adds diethyl ether, add again carbonate solution buffer (get sodium carbonate 1.91g and sodium bicarbonate 0.56g, add water and make to be dissolved into 100ml, obtain) 3ml, place jolting constantly 30 minutes; Reflux 30 minutes, divide and get ether solution, adds in the evaporating dish that fills phosphoric acid solution (5 → 1000) 1ml; The residue heating and refluxing extraction 2 times (30ml, 20ml) that adds diethyl ether, each 15 minutes, merge ether solution and put in same evaporating dish, fling to ether, residue adds 50% acetonitrile solution and dissolves, and is transferred in the 25ml measuring bottle, adds 50% acetonitrile to scale; Shake up, filter, get subsequent filtrate, obtain.
Algoscopy is accurate reference substance solution and the need testing solution 10 μ l of drawing respectively, and the injection liquid chromatography, measure, and obtains.
Table 1 Semen Arecae, Semen Arecae Prepareta medical material assay result
Above result shows, Semen Arecae, Semen Arecae Prepareta medical material all meet the pharmacopeia regulation.From the Semen Arecae to the Semen Arecae Prepareta, the content of arecoline descends approximately 60%.
Two, the different processed product pharmacodynamic studies of Semen Arecae
Carry out pharmacodynamic experiment research by Semen Arecae being given birth to the samples such as product, Semen Arecae parching to brown, Semen Arecae parching to brown, Semen Arecae stir-fry carbon early stage,
The effect of finding Semen Arecae Prepareta enhancing gastrointestinal smooth muscle is the strongest, Semen Arecae extract studied therefore the present invention focuses.
The embodiment of the present invention one:
1, Semen Arecae Prepareta 200g, add 10 times of amounts of water, extracts 3 times, and each 1.5 hours, merge extractive liquid,, filtered, and filtrate is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.
2, Semen Arecae Prepareta 200g, add 10 times of amounts of 40% ethanol, extracts 3 times, and each 1.5 hours, merge extractive liquid,, filtered, and filtrate recycling ethanol is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.
3, Semen Arecae Prepareta 200g, add 10 times of amounts of 50% ethanol, extracts 3 times, and each 1.5 hours, merge extractive liquid,, filtered, and filtrate recycling ethanol is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.
4, Semen Arecae Prepareta 200g, add 10 times of amounts of 60% ethanol, extracts 3 times, and each 1.5 hours, merge extractive liquid,, filtered, and filtrate recycling ethanol is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.
5, Semen Arecae Prepareta 200g, add 10 times of amounts of 90% ethanol, extracts 3 times, and each 1.5 hours, merge extractive liquid,, filtered, and filtrate recycling ethanol is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.
1, arecoline, guvacine assay in extract
Chromatographic condition and system suitability be take the strong cation exchange bonded silica gel as filler (SCX-strong cation-exchanging resin post); With acetonitrile-phosphoric acid solution (2 → 1000, strong ammonia solution condition pH value to 3.8), be (55:45) mobile phase; The detection wavelength is 215nm.Theoretical cam curve is calculated and should be not less than 3000 by the arecoline peak.
The preparation of reference substance precision respectively takes Arecoline hydrobromide, hydrobromic acid demethyl arecaidine standard substance 10mg, adds respectively in 2 50mL measuring bottles, with 40% dissolve with methanol standardize solution, makes arecoline mother solution, demethyl arecaidine mother solution.Accurate arecoline mother solution 1mL, the demethyl arecaidine mother solution 1mL of drawing joins in the 10mL measuring bottle respectively, with mobile phase dilution standardize solution, makes the mixing mother solution.The accurate 2mL mixing mother solution of drawing joins in the 5mL measuring bottle respectively again, with mobile phase dilution standardize solution, stand-by.
The preparation of need testing solution is got Semen Arecae (Semen Arecae Prepareta) extract 0.5g in the 50mL conical flask, precision adds 0.001M phosphoric acid solution 30mL, backflow 30min, filter, and gets 1mL filtrate and add 1mL85% phosphoric acid, with 0.45 μ m filter, filter, collect filtrate, get 1mL filtrate and add 40% methanol solution dilution in the 10mL measuring bottle, and adjust pH3-4 with 30% ammonia spirit, standardize solution, standby.
Algoscopy is accurate reference substance solution and the need testing solution 10 μ l of drawing respectively, and the injection liquid chromatography, measure, and obtains.
Arecoline, guvacine assay result in table 2 extract
| Different solvents | Arecoline (mg/g crude drug) | Guvacine (mg/g crude drug) |
| Water | 0.32 | 0.25 |
| 40% ethanol | 0.46 | 0.29 |
| 50% ethanol | 0.48 | 0.28 |
| 60% ethanol | 0.51 | 0.31 |
| 90% ethanol | 0.67 | 0.22 |
2, on the impact of smooth muscle, myenteron at the bottom of rat isolated stomach
Press cholinergic pathway sill strip test method, the de-cervical vertebra of the fasting male SD rat of 48 hours is put to death, open rapidly abdominal cavity, get the harmonization of the stomach small intestinal, in the Ke of pre-cooling-Heng Shi liquid, clean up gastric content, at the bottom of getting stomach, cut off gastral cavity along lesser gastric curvature, spread out, with shears, along the circular muscle direction, intersect at the bottom of by stomach and cut off 2～3 road otch, make it to form longer stomach bar, one section of the flesh bar of clip 1.5cm～2cm.Stomach smooth muscle one end is fixed on the glass crotch of constant temperature water bath independence inner tube bottom, can passes into mist, the other end is fixed on tension pick-up, and in constant temperature water bath, temperature is 37 ℃, makes the temperature of independent inner tube remain on 37 ℃, continues to pass into 95 ﹪ O
2With 5 ﹪ CO
2Mist.Flesh bar temperature under the preload of 2g is bathed, and within every 20 minutes, changes once fresh krebs solution (37 ℃), about 1 hour, after the spontaneous activity steadily of flesh bar, is adding medicine.The inner tube capacity is 20mL, determines that after preliminary experiment administration concentration is the 0.5g/mL crude drug, and dosage is respectively 540,80,160 μ l.Be the easypro contracting waveform of stomach bottom annular flesh under normal circumstances after waveform is steady.Be the stomach smooth muscle contracting waveform that relaxes after dosing during waveform stabilization after dosing, before next administration, with 37 ℃ of krebs solutions flushing stomach bars repeatedly, add again the medicine of another dosage after the activity of flesh bar is steady.Trace successively the impact of each medicine on the easypro contracting waveform of stomach bottom annular flesh.Get the intestinal bar, tested with method.
By test 5,10,20,40,80,160,320,640 μ l, having determined that dosage 80 μ l reach the highest substantially due to early stage, is 40-160 μ l therefore dosage is selected in this use.Result of the test in Table 3, table 4.
Table 3 different solvents is to the easypro contracting information slip of rat stomach fundus smooth muscle
Table 4 different solvents is to the easypro contracting information slip of rat myenteron
Known according to result of the test, the extract of high concentration ethanol and water extraction promotes that the gastrointestinal smooth muscle contractility is poor, and the ability that the extract that low-concentration ethanol extracts strengthens the gastrointestinal smooth muscle contraction is the strongest.
3, the impact of and intestinal propulsion emptying on normal Mouse Stomach
84 Kunming mouses evenly are divided into to 7 groups according to body weight, 12 every group, are respectively blank group, mosapride citrate group, water extraction group, 40% ethanol extraction group, 50% ethanol extraction group, 60% ethanol extraction group, 90% ethanol extraction group.Every mice is pressed the administration of 3g/kg body weight, medicinal liquid is diluted to 0.3g/mI, every mice is pressed the administration of 0.1mL/kg body weight, blank group gives the equal-volume distilled water, the mosapride citrate group is made into 1mg/mL concentration by mosapride citrate, every mice is fixed on same time administration by the 0.1mI/10g body weight every day, and 3d continues medication.Fasting 18h before last administration, after last administration finishes 40min, carry out semi-solid paste of trophism and (get the 10g sodium carboxymethyl cellulose, be dissolved in the 250mL distilled water, add respectively 16g milk powder, 8g sugar, 8g starch and 2g active carbon end, stir, be mixed with the black semisolid pastel of the about 300g of 300mL) gavage, every mice gives solid pastes by the 0.4mL/lOg body weight, after solid pastes gavage 20min, the de-neck of mice is put to death, and dissection is drawn materials.
Get before stomach pylorus and cardia ligation, get stomach, with filter paper, dry rear title full weight, then along greater gastric curvature, cut off body of stomach, dry the title net weight after washing away gastric content.The difference of stomach full weight stomach function regulating net weight of take is the gastric residue weight, and calculating the percentage ratio that the gastric residue accounts for the fills with weight of semi-solid paste is the gastric residual rate.
Get the small intestinal of pylorus to ileocecus, put into formalin solution, taking out directly is laid on blank sheet of paper gently, measure pylorus to ileocecus total length and pylorus and stick with paste the distance in forward position to black solid, the distance that pylorus to the black semisolid of take is stuck with paste forward position accounts for that pylorus carries out small intestinal length to the percentage rate of ileocecus total length as the intestinal propulsion rate and solid pastes advances measurement of length, carries out the mensuration of intestinal propulsion function.
The impact of the different extracts of table 5 and intestinal propulsion emptying on normal Mouse Stomach
* compare P<0.05 with the blank group, * * compares P<0.01 with blank group.
The Stomach residue rate of positive group and the apparent in view minimizing (P<0.05) of blank group, 90% ethanol extraction group Mouse Stomach residual rate relatively increases with blank group, water extraction group, 40% ethanol extraction group, 50% ethanol extraction group, 60% ethanol extraction group Mouse Stomach residual rate obviously reduce, and with the blank group, significant difference (P<0.01) are relatively arranged; The alvine pushing rate of positive group and the apparent in view increase of blank group (P<O.05).The blank group of water extraction group intestinal impelling ratio increases, but not statistically significant.40% ethanol extraction group, 50% ethanol extraction group, 60% ethanol extraction group alvine pushing rate increase, and with the blank group, statistical significance (P<O.05) are relatively arranged.Illustrate that 40% ethanol extraction group, 50% ethanol extraction group, 60% ethanol extraction group can obviously improve gastric emptying and the intestinal propulsion rate of mice.
Claims (9)
1. promote the Semen Arecae Prepareta extract of gastrointestinal peristalsis, it is characterized in that: described Semen Arecae Prepareta extract adopts following method to make: Semen Arecae Prepareta adopts 30%～70%v/v ethanol extraction 1～3 time, each 0.5～2 hour, merge extractive liquid,, filter, filtrate is concentrated into dry, obtains.
2. promote the Semen Arecae Prepareta extract of gastrointestinal peristalsis, it is characterized in that: described Semen Arecae Prepareta extract adopts following method to make: Semen Arecae Prepareta adopts 6～16 times of amounts of 30%～70%v/v ethanol to extract 1～3 time, each 0.5～2 hour, merge extractive liquid,, filter, filtrate is concentrated into the clear paste that relative density is 1.08～1.20, and drying obtains.
3. Semen Arecae Prepareta extract according to claim 1 and 2, is characterized in that: the ethanol that described ethanol is 40%～60%v/v.
4. Semen Arecae Prepareta extract according to claim 1 and 2 is characterized in that: by the Semen Arecae Prepareta extract, add common medicinal supplementary material, preparation process is made oral formulations or ejection preparation routinely.
5. Semen Arecae Prepareta extract according to claim 4, it is characterized in that: described oral formulations is tablet, capsule, granule, drop pill or oral liquid.
6. Semen Arecae Prepareta extract according to claim 4, it is characterized in that: described ejection preparation is freeze-dried powder or liquid drugs injection.
7. the preparation method of the Semen Arecae Prepareta extract of promotion gastrointestinal peristalsis claimed in claim 1, it is characterized in that: step is as follows: Semen Arecae Prepareta adopts 30%～70%v/v ethanol extraction 1～3 time, each 0.5～2 hour, merge extractive liquid,, filter, filtrate is concentrated into dry, gets final product.
8. the preparation method of the Semen Arecae Prepareta extract of promotion gastrointestinal peristalsis claimed in claim 2, it is characterized in that: step is as follows: Semen Arecae Prepareta adopts 6～16 times of amounts of 30%～70%v/v ethanol to extract 1～3 time, each 0.5～2 hour, merge extractive liquid,, filter, filtrate is concentrated into the clear paste that relative density is 1.08～1.20, and drying gets final product.
9. according to the preparation method of the Semen Arecae Prepareta extract of the described promotion gastrointestinal peristalsis of claim 7 or 8, it is characterized in that: the ethanol that described ethanol is 40%～60%v/v.
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| CN110609005A (en) * | 2019-10-22 | 2019-12-24 | 海南大学 | Antioxidant activity detection and compound application of plant-derived antioxidant |
| WO2022178913A1 (en) * | 2021-02-26 | 2022-09-01 | 海南葫芦娃药业集团股份有限公司 | Areca nut extract capable of improving gastric motility, preparation process therefor, and application thereof |
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| WO2022178913A1 (en) * | 2021-02-26 | 2022-09-01 | 海南葫芦娃药业集团股份有限公司 | Areca nut extract capable of improving gastric motility, preparation process therefor, and application thereof |
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Application publication date: 20131204 |