CN1315504C - Extract for treating functional indigestion and its medicine composition - Google Patents
Extract for treating functional indigestion and its medicine composition Download PDFInfo
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- CN1315504C CN1315504C CNB2005101176505A CN200510117650A CN1315504C CN 1315504 C CN1315504 C CN 1315504C CN B2005101176505 A CNB2005101176505 A CN B2005101176505A CN 200510117650 A CN200510117650 A CN 200510117650A CN 1315504 C CN1315504 C CN 1315504C
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Abstract
The present invention discloses an extract for curing functional indigestion and a medicine composition thereof. An extract takes white atractylodes rhizome, immature bitter orange, Chinese thorowax root and haws as raw materials and is prepared by the method containing the following steps: (1) part of the white atractylodes rhizome is taken and is crushed into fine powder; (2) the immature bitter orange and the haws are extracted by alkali alcohol, and the pH value of an extracting solution is mixed by acid and then the extracting solution is concentrated into extractum; (3) the immature bitter orange, medicine dregs of the haw, the Chinese thorowax root and residual white atractylodes rhizome which are extracted by step(2) are extracted by water; the pH value of the extracting solution is mixed into neutrality by acid; the extracting solution is concentrated and is added with alcohol to cause alcohol contents to reach 50 to 80%, and supernatant liquid is leached and is concentrated into extractum; (4) fine powder which is obtained by step (1) and the extractum which is obtained by steps (2) and (3) are combined and evenly mixed.
Description
Technical field
The present invention relates to a kind of Chinese medicine compound extract and preparation and detection method, specifically, relate to a kind of extract for the treatment of functional dyspepsia and pharmaceutical composition thereof and purposes, detection method.Belong to field of medicaments.
Background technology
Functional dyspepsia is a kind of global frequently-occurring disease, commonly encountered diseases, and the symptom of functional dyspepsia mainly is abdominal distention, stomachache, feel sick, vomiting and acid regurgitation etc., and the inducement of morbidity mainly is that gastric motility is not normal, stomach perception allergy.Hesperian hospital admission patient's statistics shows that FD patient is 2%～3% of medical patient's sum, accounts for 20%～40% of digestive system disease.Account for gastrointestinal special outpatient clinic patient more than 1/3 according to domestic statistics.No matter analysis expert, medicine for stomach dynamic are at home or in the world, are brand-new field, and whole research also just has only the time more than 10 years, is the field of chemical medicine basically.There is 3,000,000,000 yuan the market share in China digestive tract power reinforcing medicine market.Have only minority chemical drugss such as motilium, cisapride at present, so Chinese medicine is very big in this field market opportunity.
The Rhizoma Atractylodis Macrocephalae is the dry rhizome of feverfew Rhizoma Atractylodis Macrocephalae Atractylodes macrocephala Koidz..Bitter in the mouth, sweet, warm in nature.Mainly contain invigorating the spleen and benefiting QI, dampness diuretic, hidroschesis, antiabortive effect.Be used for insufficiency of the spleen lack of appetite, abdominal distention is had loose bowels, phlegm retention vertigo and palpitation, edema, spontaneous perspiration, the treatment of frequent fetal movement.The Rhizoma Atractylodis Macrocephalae contains volatile oil about 1.4%, main component is atractylol (atractylol), atractylone (atractylon), selinene (selina-4 (15)-7 (11)-dine-8-one), sesquiterpene lactones chemical compound atractylodes lactone (atractylenolide) I, II, III etc.Also contain multiple acetylene compound in the Rhizoma Atractylodis Macrocephalae.In addition, also contain vitamin A in the Rhizoma Atractylodis Macrocephalae.Pharmacological effect studies show that Rhizoma Atractylodis Macrocephalae decoct can make rabbit intestine in vitro spontaneous activity tonicity raise, and shrinkage amplitude strengthens, obviously antagonism Ach and BaCl
2Due to the intestinal tube spasm.Experimental observation has been arranged than of the influence of heavy dose of Rhizoma Atractylodis Macrocephalae water decoction (0.1mg/10g body weight) to the mice gastrointestinal propulsion, the result shows: it is 73.28 ± 5.59 that Rhizoma Atractylodis Macrocephalae water decoction 0.1mg/10g body weight advances percent to the mice gastrointestinal, matched group is 43.68 ± 1.25, gastrointestinal advances percent to increase by 29.6% (P＜0.01), shows that Rhizoma Atractylodis Macrocephalae water decoction 0.1mg/10g body weight has obvious booster action to the mice gastrointestinal propulsion; Rhizoma Atractylodis Macrocephalae decoct was irritated stomach one month, can promote the mice weight increase and strengthen swimming endurance.It is reported that the Rhizoma Atractylodis Macrocephalae can strengthen the phagocytic function of reticuloendothelial system.When leukopenia, the Rhizoma Atractylodis Macrocephalae has the leukogenic effect Rhizoma Atractylodis Macrocephalae can also improve lymhocyte transformation rate and natural rosette formation rate, promotes cellular immune function, and obviously increases the content of IgG; External, the Rhizoma Atractylodis Macrocephalae can strengthen the function of leukocytes phagocytic staphylococcus aureus, and the effect that the Rhizoma Atractylodis Macrocephalae has " strengthening the spleen and stomach, strong health " and improves body resistance against diseases is described; Experiment in vitro shows that the neutral oil in the Rhizoma Atractylodis Macrocephalae volatile oil has obvious inhibitory action to esophageal cancer cell.
Fructus Aurantii Immaturus is the dry young fruit of rutaceae Citrus aurantium Linn. Citrus aurantium L. and variety or Fructus Citri sinensis Citrussinensis Osbeck.Bitter in the mouth, suffering, acid, warm in nature.Return spleen, stomach warp.The dispelling the stagnated QI removing food stagnancy is arranged, the effect of the diffusing painful abdominal mass of reducing phlegm.Be used for stopping in stagnant, the feeling of fullness distending pain, heavy behind the dysentery, constipation, the expectorant vapour lock thoracic obstruction that stagnates, blocked-up chest; Gastroptosis, proctoptosis, the treatment of uterine prolapse.Main chemical compositions have hesperidin (Hesperidin), neohesperidin (Neohesperidin), naringin (Naringin), lonicerin (Lonicerin), rhoifolin (Rhoifolin), Neosynephrine (oxedrine, Synephrine) etc.In addition, also fatty, protein, carbohydrate, carotene, riboflavin, calcium, phosphorus, ferrum etc.The isolated frog heart perfusion experiment shows that the Fructus Aurantii Immaturus decoct can make heart contractility strengthen, and amplitude increases.It is strong that Fructus Aurantii Immaturus decocting liquid makes the gastrointestinal of stomach, intestinal fistula Canis familiaris L. shrink the rhythm and pace of moving things, is excitatory state, but suppress Canis familiaris L. in the body bowel movement.Fructus Aurantii Immaturus has the intestinal smooth muscle of enhancing tensity and position phasic property contractile function; The Fructus Aurantii Immaturus decoct all has appreciable stimulating action to the fistula of uterus that unpregnancy reaches pregnant rabbit isolated uterine, uterus on the throne and unpregnancy rabbit, and the uterus rhythm and pace of moving things is increased.
Radix Bupleuri is the dry root of umbelliferae bupleurum Bupleurum chinense DC..Bitter in the mouth, cold nature.Return liver, gallbladder meridian.Reconciling superficies and interior is arranged, soothing the liver, the effect of yang invigorating.Be used for cold, fever, alternate attack of chill and fever, distending pain in the chest and hypochondrium, menoxenia; Uterine prolapse, the treatment of proctoptosis.The Radix Bupleuri master contains volatile oil, Saponin, organic acid, alcohols etc.The test of rat pylorus ligation shows that kaikosides can obviously suppress gastric secretion, and pepsin activity is reduced, and the tendency that reduces ulcer coefficient is arranged.Bupleurum preparation has significant protective effect to the experimental tremulous pulse hepatic injury due to bacillary (antityphoid vaccine), carbon tetrachloride and penicillin mould.
Fructus Crataegi is the dry mature fruit of rosaceous plant Fructus Pyri Pashiae Crataegus pinnatifida Bge.var.major N.E.Br. or Fructus Crataegi Crataegus pinnatifida Bge..Sour in the mouth, sweet, slightly warm in nature.Return spleen, stomach, Liver Channel.Promoting digestion and invigorating the stomach is arranged, the effect of circulation of qi promoting dissipating blood stasis.Be used for meat stagnation, gastral cavilty distension, dysentery stomachache, congestion amenorrhea, postpartum stagnation, trusted subordinate's twinge, hernia pain; Diseases such as hyperlipemia.Fructus Crataegi mainly contains Crataegolic acid (Crataegolic acid, maslinic acid), organic acid such as chlorogenic acid (Chlorogenic acid), ursolic acid, oleanolic acid, malic acid, flavone compound has Quercetin, vitexin (Vitexin) etc., in addition, still contain stigmasterol, vanillin, carotene, vitamin, glycoside, saccharide, fat, tannin and calcium, phosphorus, ferrum etc.Pharmacological effect studies show that, can increase enzyme in the stomach, facilitating digestion behind the Fructus Crataegi clothes; Its contained lipase also can promote the digestion of fatty food stagnation; Experimentation proves that Fructus Crataegi has stronger antibacterial action to will Hayes, Fu Shi, Song Nei Shi, Si Mishishi dysentery bacterium; Green pus liver bacterium, staphylococcus aureus, escherichia coli, Bacillus proteus, anthrax bacillus, group B streptococcus, diphtheria corynebacterium, Bacillus typhi all there is antibacterial action; In addition, Fructus Crataegi also has blood fat reducing, increases coronary flow, heart tonifying, diuresis, antioxidation, raise immunity and protective effect on cancer risk.
Summary of the invention
Based on the research of prior art, the invention provides a kind of Chinese medicine compound extract that is used for the treatment of functional dyspepsia, and comprise the pharmaceutical composition of this extract as active constituents of medicine, and their purposes, and its quality of medicinal material detection method is provided.Take following technical scheme:
Extract of the present invention, make by following bulk drugs: the Rhizoma Atractylodis Macrocephalae, Fructus Aurantii Immaturus, Radix Bupleuri and Fructus Crataegi, by weight calculating the Rhizoma Atractylodis Macrocephalae: Fructus Aurantii Immaturus: Radix Bupleuri: Fructus Crataegi=1～4: 1～3: 1～2: 1～2, this extract prepares by the method that comprises following steps:
(1) gets the Rhizoma Atractylodis Macrocephalae partly, be ground into fine powder;
(2) extract Fructus Aurantii Immaturus and Fructus Crataegi with alkaline alcohol, to neutral, reconcentration is to cream with sour adjust pH for extracting solution;
(3) Fructus Aurantii Immaturus, the medicinal residues of Fructus Crataegi and the Rhizoma Atractylodis Macrocephalae of Radix Bupleuri and surplus after step (2) is extracted use water extraction, extracting solution with sour adjust pH to neutral, concentrated, add ethanol and make and contain pure measuring and reach 50～80%, the leaching supernatant is concentrated into cream;
(4) cream of the fine powder of combining step (1) gained and step (2), (3) gained, mixing.
Above-mentioned described extract, the Rhizoma Atractylodis Macrocephalae is wherein preferably used Rhizoma Atractylodis Macrocephalae (parched).
Above-mentioned described extract, wherein said alkaline alcohol, alkali are sodium hydroxide or potassium hydroxide, perhaps the methoxide of sodium or potassium, ethylate, carbonate or bicarbonate;
Above-mentioned described extract, wherein said alkaline alcohol, alcohol is preferably ethanol for containing the alcohol of 1～3 carbon atom.
Above-mentioned described extract, wherein said acid are mineral acid, and example hydrochloric acid, phosphoric acid, sulphuric acid etc. perhaps are organic acid, as citric acid etc.; Be preferably hydrochloric acid.
As preferably, above-mentioned described extract prepares by the method that comprises following steps:
(1) gets 1/3 Rhizoma Atractylodis Macrocephalae of measuring and be ground into fine powder;
(2) Fructus Aurantii Immaturus, Fructus Crataegi with 65% ethanol that contains 1% sodium hydroxide as solvent in 25 ℃ ± 2 ℃ lixiviates three times, each 24 hours, merge immersion, to neutral, reclaim ethanol with the hydrochloric acid adjust pH, being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃);
(3) Fructus Aurantii Immaturus, the medicinal residues of Fructus Crataegi and the Rhizoma Atractylodis Macrocephalae of Radix Bupleuri and surplus after step (2) is extracted decoct with water each 0.5 hour three times, added for the first time behind the water merceration 0.5 hour, with the hydrochloric acid adjust pH to neutral, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.20～1.35 (50 ℃), adds ethanol, makes to contain alcohol amount and reach 70%, left standstill 24 hours, the leaching supernatant reclaims ethanol, and being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃);
(4) thick paste of drying steps (2) and (3) gained is pulverized, and carries out mixing with the Rhizoma Atractylodis Macrocephalae fine powder of step (1) gained.
A kind of pharmaceutical composition of the present invention, it comprises above-mentioned described extract as active constituents of medicine, with adjuvant pharmaceutically commonly used, by the pharmaceutical preparation technology of routine, makes pharmaceutical preparation.
Wherein, as preferred version, above-mentioned pharmaceutical composition is a dispersible tablet.Described dispersible tablet calculates by weight, 337.5 parts of Rhizoma Atractylodis Macrocephalae (parched)s, and 225 parts of Fructus Aurantii Immaturuss, 168.75 parts of Radix Bupleuri, 168.75 parts of Fructus Crataegis make 1000 as follows:
(1) gets 1/3 Rhizoma Atractylodis Macrocephalae of measuring and be ground into fine powder;
(2) Fructus Aurantii Immaturus, Fructus Crataegi with 65% ethanol that contains 1% sodium hydroxide as solvent in 25 ℃ ± 2 ℃ lixiviates three times, each 24 hours, merge immersion, to neutral, reclaim ethanol with the hydrochloric acid adjust pH, being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃);
(3) Fructus Aurantii Immaturus, the medicinal residues of Fructus Crataegi and the Rhizoma Atractylodis Macrocephalae of Radix Bupleuri and surplus after step (2) is extracted decoct with water each 0.5 hour three times, added for the first time behind the water merceration 0.5 hour, with the hydrochloric acid adjust pH to neutral, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.20～1.35 (50 ℃), adds ethanol, makes to contain alcohol amount and reach 70%, left standstill 24 hours, the leaching supernatant reclaims ethanol, and being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃);
(4) thick paste of drying steps (2) and (3) gained is pulverized, and carries out mixing with the Rhizoma Atractylodis Macrocephalae fine powder of step (1) gained;
(5) add microcrystalline Cellulose and correctives in the fine powder behind the mixing of step (4) gained, make granule, drying adds lubricant and low-substituted hydroxypropyl cellulose, is pressed into 1000.
Wherein, microcrystalline Cellulose be in disintegrating agent, with respect to the weight of the fine powder behind the described mixing, its consumption 35%～60%, preferred 45%～50%.
Wherein, low-substituted hydroxypropyl cellulose is for adding disintegrating agent, with respect to the weight of the fine powder behind the described mixing, and its consumption 5%～15%, preferred 10%～12%.
Wherein, described correctives can be correctives pharmaceutically commonly used, steviosin for example, and saccharin sodium, aspartame etc. are preferably aspartame, and the weight of the fine powder of its consumption after with respect to described mixing is 0.5%～2%, preferred 1%.
Wherein, described lubricant can be lubricant pharmaceutically commonly used, Pulvis Talci for example, magnesium stearate, stearic acid etc.; Be preferably magnesium stearate, the weight of the fine powder of its consumption after with respect to described mixing is 0.2%～1%, preferred 0.5%.
Wherein, system during granule available water, ethanol etc. as solvent, preferred water, with respect to the weight of the fine powder behind the described mixing, amount of water is 10%～35% during the system granule, preferred 20%～25%.
Above-mentioned described extract, pharmaceutical composition, perhaps dispersible tablet, can be by comprising with the next item down or the step more than as quality determining method:
(1) discriminating of the Rhizoma Atractylodis Macrocephalae: sample extracts with petroleum ether, extract carries out thin layer and differentiates that lamellae is a silica gel g thin-layer plate, and developing solvent is petroleum ether (60～90 ℃)-ethyl acetate (17.5: 2.5), developer is 10% ethanol solution of sulfuric acid, with Rhizoma Atractylodis Macrocephalae medical material in contrast;
(2) discriminating of Fructus Aurantii Immaturus: sample extracts with methanol, extract carries out thin layer and differentiates, lamellae is the silica gel g thin-layer plate with the preparation of 0.5% sodium hydroxide, developing solvent is the upper solution of n-butyl alcohol-glacial acetic acid-water (4: 1: 5), developer is 3% aluminum chloride alcoholic solution, with the Fructus Aurantii Immaturus medical material in contrast:
(3) discriminating of Radix Bupleuri: sample extracts with methanol, the water saturated n-butanol extraction of extract, the washing of n-butanol extracting liquid reuse ammonia solution, discard ammoniacal liquor, the saturated water washing of n-butyl alcohol of n-butyl alcohol liquid, discard water liquid, n-butyl alcohol liquid evaporate to dryness, residue adds methanol makes dissolving, as need testing solution, carries out thin layer and differentiates, lamellae is a silica gel g thin-layer plate, developing solvent is lower floor's solution of chloroform-methanol-water (7: 3: 1), and developer is the sulfuric acid solution of 2% paradime thylaminobenzaldehyde, with the Radix Bupleuri medical material in contrast;
(4) discriminating of Fructus Crataegi: the samples with water heating extraction, extracting solution adjust pH to 2 is put cold, filter filtering residue oven dry, porphyrize, add diethyl ether merceration 24 hours filters, and filtrate is waved most ether, residue adds dehydrated alcohol makes dissolving, as need testing solution, carries out thin layer and differentiates, lamellae is a silica gel g thin-layer plate, developing solvent is cyclohexane extraction-acetone-ethyl acetate (12: 3: 1), and developer is 10% ethanol solution of sulfuric acid, with ursolic acid in contrast;
(5) high effective liquid chromatography for measuring Hesperidin (C
23H
34O
15) content, wherein, be filler with octadecylsilane chemically bonded silica, be mobile phase with acetonitrile-0.01% phosphoric acid solution (18: 82), the detection wavelength is 283nm, number of theoretical plate calculates by the Hesperidin peak should be not less than 1500.
Above-mentioned described extract, pharmaceutical composition, perhaps dispersible tablet can be used for preparing the medicine for the treatment of functional dyspepsia.Described medicine has invigorating the spleen and regulating the stomach, and the function of painful abdominal mass of disappearing of regulating the flow of vital energy can be used as digestive tract power reinforcing medicine, the functional dyspepsia that be used for the treatment of that gastric motility is not normal, stomach perception allergy etc. causes, and disease is seen abdominal distention, stomachache, is felt sick, vomiting and acid regurgitation etc.
In the prescription, the Rhizoma Atractylodis Macrocephalae returns taste through being monarch drug, and spleen invigorating helps the fortune removing dampness; Fructus Aurantii Immaturus returns the liver stomach through being ministerial drug, therapeutic method to keep the adverse QI flowing downwards intestinal stasis relieving, relieving distension and oppression; Adjuvant drug Radix Bupleuri both can rise the clearing heat in QI system of taste, but the pent-up of soothing liver-QI gas again, and with Fructus Aurantii Immaturus mutually 5, ascending the clear and descending the turbid is begged to surrender in the liter, makes mechanism of qi and smooth.Another adjuvant drug hawthorn digesting spleen invigorating is share with the monarch drug Rhizoma Atractylodis Macrocephalae, with the long-pending fortuneization that helps that helps digestion.Show that from the result of zoopery and initial stage clinical observation aspect functional dyspepsia symptoms such as the insufficiency of the spleen stagnation of QI of treatment, incoordination between the liver and stomach receive better curative effect.
The zoopery result also points out before clinical: extract of the present invention or pharmaceutical composition can promote normally to reach the gastric emptying that atropine is handled mice; Increase rat total acidity gastric juice and pepsin activity; Accelerate intestinal propulsion motion normal and atropine processing mice.In addition, this product also has certain sedation.
The specific embodiment
Further illustrate content of the present invention below by embodiment.But the scope of the present invention is not limited to following embodiment.
Embodiment 1
Get Fructus Aurantii Immaturus 91.5g, Fructus Crataegi 66g, add 65% ethanol that contains 1% sodium hydroxide and make solvent in 25 ℃ ± 2 ℃ lixiviates three times, add for the first time 6 times of amount ethanol, lixiviate 24 hours adds 4 times of amount ethanol for the second time, for the third time, lixiviate 12 hours, merge lixiviating solution, filter, filtrate is extremely neutral with the hydrochloric acid adjust pH, reclaim ethanol, be concentrated into the concentrated solution that every 1ml is equivalent to 0.5g Fructus Aurantii Immaturus crude drug.Get the concentrated solution that is equivalent to 0.03g Fructus Aurantii Immaturus crude drug, the accurate title, decide, and puts in the tool plug conical flask, the accurate methanol 50ml that adds, close plug claims to decide weight, supersound process (power 250W, frequency 50kHz) 40 minutes is put cold, claim to decide weight again, supply the weight that subtracts mistake with methanol, shake up, filter, get subsequent filtrate 10 μ l, high performance liquid chromatography records content of hesperidin 12.55%.
Embodiment 2
Get Fructus Aurantii Immaturus 91.5g, Fructus Crataegi 66g, add 65% ethanol that contains 1% sodium hydroxide and make solvent in 25 ℃ ± 2 ℃ lixiviates three times, each 24 hours, add for the first time 6 times of amount ethanol, add 4 times of amount ethanol for the second time, for the third time, merge lixiviating solution, filter, filtrate to neutral, is reclaimed ethanol with the hydrochloric acid adjust pH, is concentrated into the concentrated solution that every 1ml is equivalent to 0.5g Fructus Aurantii Immaturus crude drug.Record content of hesperidin 13.98% according to embodiment one same procedure.
Embodiment 3
Get Fructus Aurantii Immaturus 91.5 g, Fructus Crataegi 66g, add 65% ethanol that contains 1% sodium hydroxide and make solvent in 25 ℃ ± 2 ℃ lixiviate secondaries, add for the first time 6 times of amount ethanol, lixiviate 48 hours, 4 times of amount ethanol for the second time, lixiviate 24 hours, merge lixiviating solution, filter, filtrate is extremely neutral with the hydrochloric acid adjust pH, reclaim ethanol, be concentrated into the concentrated solution that every 1ml is equivalent to 0.5g Fructus Aurantii Immaturus crude drug.Record content of hesperidin 12.70% according to embodiment one same procedure.
Embodiment 4
Get the medicinal residues after embodiment 2 lixiviates, with Rhizoma Atractylodis Macrocephalae 91.5g, Radix Bupleuri 66g mixes, put in the electric heating extraction pot, decoct with water three times, each 0.5 hour, add 10 times of water gagings for the first time, merceration 0.5 hour, to neutral, add 8 times of water gagings for the second time, for the third time, collecting decoction with the hydrochloric acid adjust pH, filter, filtrate is concentrated into the concentrated solution that every 1ml is equivalent to the total medical material of 1g.Take by weighing the concentrated solution that is equivalent to the total medical material of 10.5g and add water to 20ml, extract 5 times, each 15ml with water saturated n-butyl alcohol jolting, merge n-butanol extracting liquid, put in the evaporating dish of having weighed and evaporate, be dried to constant weight, the accurate title, decide, and it is heavy to calculate extract, and n-butanol extract weighs 3.47%.
Embodiment 5
Get the medicinal residues after embodiment 2 lixiviates, with Rhizoma Atractylodis Macrocephalae 91.5g, Radix Bupleuri 66g mixes, put in the electric heating extraction pot, decoct with water secondary, add 10 times of water gagings, merceration 0.5 hour for the first time, extremely neutral with the hydrochloric acid adjust pH, decocted 1 hour, 8 times of water gagings decoct 0.5 hour collecting decoction for the second time, filter, filtrate is concentrated into the concentrated solution that every 1ml is equivalent to the total medical material of 1g.Record n-butanol extract according to embodiment 4 same procedure and weigh 3.14%.
Embodiment 6
Get the Rhizoma Atractylodis Macrocephalae (stir-fry) 170.65g, Fructus Aurantii Immaturus 114.4g, Radix Bupleuri 82.5g, Fructus Crataegi 82.5g.Get 1/3 Rhizoma Atractylodis Macrocephalae, be ground into fine powder; Fructus Aurantii Immaturus, Fructus Crataegi two flavor medical materials are made solvent in 25 ℃ ± 2 ℃ lixiviates three times with 65% ethanol that contains 1% sodium hydroxide, and each 24 hours, merge immersion, to neutral, reclaim ethanol with the hydrochloric acid adjust pH, being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃); Medicinal residues and all the other Radix Bupleuri, the Rhizoma Atractylodis Macrocephalae decoct with water three times, each 0.5 hour, add for the first time behind the water merceration 0.5 hour, to neutral, collecting decoction filters with the hydrochloric acid adjust pH, filtrate is concentrated into the clear paste that relative density is 1.20～1.35 (50 ℃), adds ethanol, makes to contain alcohol amount and reach 65%, left standstill 24 hours, the leaching supernatant reclaims ethanol, being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃), dry above-mentioned two kinds of thick pastes are pulverized, with Rhizoma Atractylodis Macrocephalae fine powder mixing.
Embodiment 7
Get the Rhizoma Atractylodis Macrocephalae (stir-fry) 337.5g, Fructus Aurantii Immaturus 225g, Radix Bupleuri 168.75g, Fructus Crataegi 168.75g.Get 1/3 Rhizoma Atractylodis Macrocephalae, be ground into fine powder; Fructus Aurantii Immaturus, Fructus Crataegi two flavor medical materials are made solvent in 25 ℃ ± 2 ℃ lixiviates three times with 65% ethanol that contains 1% sodium hydroxide, and each 24 hours, merge immersion, to neutral, reclaim ethanol with the hydrochloric acid adjust pH, being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃); Medicinal residues and all the other Radix Bupleuri, the Rhizoma Atractylodis Macrocephalae decoct with water three times, each 0.5 hour, add for the first time behind the water merceration 0.5 hour, to neutral, collecting decoction filters with the hydrochloric acid adjust pH, filtrate is concentrated into the clear paste that relative density is 1.20～1.35 (50 ℃), adds ethanol, makes to contain alcohol amount and reach 70%, left standstill 24 hours, the leaching supernatant reclaims ethanol, being concentrated into relative density is the thick paste of 1.30～1.35 (50 ℃), dry above-mentioned two kinds of thick pastes are pulverized, with Rhizoma Atractylodis Macrocephalae fine powder mixing.
Embodiment 8
Get the fine powder behind the mixing of embodiment 7 gained,, add 45% microcrystalline Cellulose and 1% aspartame with respect to fine powder amount, add 20% water and make granule, drying adds the low-substituted hydroxypropyl cellulose of 0.5% magnesium stearate and 10%, be pressed into 1000, make dispersible tablet.
Embodiment 9
Get the fine powder behind the mixing of embodiment 7 gained,, add 35% microcrystalline Cellulose and 1% aspartame with respect to fine powder amount, add 15% water and make granule, drying adds the low-substituted hydroxypropyl cellulose of 0.5% magnesium stearate and 15%, be pressed into 1000, make dispersible tablet.
Embodiment 10:(contrast test)
Sample 1: with embodiment 8, but do not add low-substituted hydroxypropyl cellulose, make dispersible tablet.
Sample 2: with embodiment 8, low-substituted hydroxypropyl cellulose is taked interior addition, promptly adds before granulation with microcrystalline Cellulose, makes dispersible tablet.
Embodiment 11:(tests disintegration)
Method: check according to Chinese Pharmacopoeia version in 2005 inspection technique disintegration (appendix XII A).The result is as shown in table 1.
Table 1 disintegration
| Sample | Technology | Disintegration |
| Embodiment 8 embodiment 9 embodiment 10 samples 1 embodiment 10 samples 2 | Adding low-substituted hydroxypropyl cellulose in the microcrystalline cellulose adds and adds low-substituted hydroxypropyl cellulose in the microcrystalline cellulose and add to add in the microcrystalline cellulose to add in the low-substituted hydroxypropyl cellulose in the microcrystalline cellulose and add | 50 seconds 60 seconds 240 seconds 200 seconds |
Embodiment 12
Get 6 of the dispersible tablets of embodiment 8, porphyrize adds petroleum ether 20ml, jolting 2 minutes, and merceration 2 hours filters, and filtrate evaporate to dryness, residue add petroleum ether 1ml makes dissolving, as need testing solution.Other gets Rhizoma Atractylodis Macrocephalae control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (Chinese Pharmacopoeia version appendix in 2005 VI B), draw each 8 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with petroleum ether (60～90 ℃)-ethyl acetate (17.5: 2.5) is developing solvent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing in 105 ℃, puts under the ultra-violet lamp (365nm) and inspects.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
Embodiment 13
Get 6 of the dispersible tablets of embodiment 8, porphyrize adds methanol 20ml, puts in the water-bath reflux 20 minutes, filters, and filtrate evaporate to dryness, residue add methanol 5ml makes dissolving, as need testing solution.Other gets Fructus Aurantii Immaturus control medicinal material 0.5g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (Chinese Pharmacopoeia version appendix in 2005 VI B), draw each 3 μ l of above-mentioned two kinds of solution, put respectively on the silica gel g thin-layer plate of same usefulness 0.5% sodium hydroxide preparation, upper solution with n-butyl alcohol-glacial acetic acid-water (4: 1: 5) is developing solvent, launch, take out, dry, spray is put under the ultra-violet lamp (365nm) and is inspected with 3% aluminum chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
Embodiment 14
Get 6 of the dispersible tablets of embodiment 8, porphyrize adds methanol 40ml, puts in the water-bath reflux 30 minutes, filter, filtrate evaporate to dryness, residue add water 20ml makes dissolving, extract 3 times with water saturated n-butyl alcohol jolting, each 15ml merges n-butanol extracting liquid, add ammonia solution washing 2 times, each 20ml discards ammoniacal liquor, the saturated water washing of n-butyl alcohol 2 times of n-butyl alcohol liquid, each 20ml discards water liquid, n-butyl alcohol liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Radix Bupleuri control medicinal material 0.5g, adds methanol 20ml, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (Chinese Pharmacopoeia version appendix in 2005 VI B), draw need testing solution 10 μ l, control medicinal material solution 2 μ l, putting respectively on same silica gel g thin-layer plate, is developing solvent with lower floor's solution of chloroform-methanol-water (7: 3: 1), launches below 10 ℃, take out, dry, spray is with the sulfuric acid solution of 2% paradime thylaminobenzaldehyde, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
Embodiment 15
Get 6 of the dispersible tablets of embodiment 8, porphyrize adds water 30ml, heats adjust pH to 2 10 minutes, put coldly, filter, the filtering residue oven dry, porphyrize, 20ml adds diethyl ether, merceration 24 hours filters, and filtrate is waved most ether, and residue adds dehydrated alcohol 1ml makes dissolving, as need testing solution.Other gets the ursolic acid reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 0.2mg, in contrast product solution.Test according to thin layer chromatography (Chinese Pharmacopoeia version appendix in 2005 VI B), draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-acetone-ethyl acetate (12: 3: 1) is developing solvent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing in 105 ℃.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
Embodiment 16
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every 1ml contains 0.1mg, promptly.
The preparation sample thief of need testing solution is an amount of, and porphyrize is got about 0.15g, the accurate title, decide, and puts in the tool plug conical flask, the accurate methanol 50ml that adds, close plug claims to decide weight, supersound process (power 250W, frequency 50kHz) 40 minutes, put coldly, claim to decide weight again, supply the weight that subtracts mistake with methanol, shake up, filter, get subsequent filtrate, promptly.
The chromatographic determination condition
Chromatographic column: Dikma C
18, 5 μ m, 4.60 * 150mm rustless steel packed column.
Column temperature: 35 ℃
Flow velocity: 1.0ml/min
Detect wavelength: 283nm
Sample size: 10ul
Mobile phase: acetonitrile-0.01% phosphoric acid solution (18: 82).
Record in embodiment 8 and the 9 dispersible tablet samples, content of hesperidin is respectively 22.57mg/ sheet and 21.65mg/ sheet.
Claims (10)
1. an extract is made by following bulk drugs: the Rhizoma Atractylodis Macrocephalae, Fructus Aurantii Immaturus, Radix Bupleuri and Fructus Crataegi, by weight calculating the Rhizoma Atractylodis Macrocephalae: Fructus Aurantii Immaturus: Radix Bupleuri: Fructus Crataegi=1～4: 1～3: 1～2: 1～2, it is characterized in that this extract prepares by the method that comprises following steps:
(1) gets the Rhizoma Atractylodis Macrocephalae partly, be ground into fine powder;
(2) extract Fructus Aurantii Immaturus and Fructus Crataegi with alkaline alcohol, to neutral, reconcentration is to cream with sour adjust pH for extracting solution;
(3) Fructus Aurantii Immaturus, the medicinal residues of Fructus Crataegi and the Rhizoma Atractylodis Macrocephalae of Radix Bupleuri and surplus after step (2) is extracted use water extraction, extracting solution with sour adjust pH to neutral, concentrated, add ethanol and make and contain pure measuring and reach 50～80%, the leaching supernatant is concentrated into cream;
(4) cream of the fine powder of combining step (1) gained and step (2), (3) gained, mixing.
2. extract according to claim 1, the wherein said Rhizoma Atractylodis Macrocephalae are Rhizoma Atractylodis Macrocephalae (parched).
3. extract according to claim 1 and 2, the alkali of wherein said alkaline alcohol are hydroxide, methoxide, ethylate, carbonate or the bicarbonate of sodium or potassium, and the alcohol of alkaline alcohol is the alcohol that contains 1～3 carbon atom.
4. extract according to claim 1 and 2, wherein said acid are mineral acid or organic acid.
5. according to each described extract of claim 1-4, wherein said extract prepares by the method that comprises following steps:
(1) gets 1/3 Rhizoma Atractylodis Macrocephalae of measuring and be ground into fine powder;
(2) Fructus Aurantii Immaturus, Fructus Crataegi with 65% ethanol that contains 1% sodium hydroxide as solvent in 25 ℃ ± 2 ℃ lixiviates three times, each 24 hours, merge immersion, to neutral, reclaim ethanol with the hydrochloric acid adjust pH, 1.30～1.35 thick paste when being concentrated into relative density and being 50 ℃;
(3) Fructus Aurantii Immaturus, the medicinal residues of Fructus Crataegi and the Rhizoma Atractylodis Macrocephalae of Radix Bupleuri and surplus after step (2) is extracted decoct with water each 0.5 hour three times, added for the first time behind the water merceration 0.5 hour, with the hydrochloric acid adjust pH to neutral, collecting decoction, filter, 1.20～1.35 clear paste added ethanol when filtrate was concentrated into relative density and is 50 ℃, made to contain the alcohol amount and reach 70%, left standstill 24 hours, the leaching supernatant reclaims ethanol, 1.30～1.35 thick paste when being concentrated into relative density and being 50 ℃;
(4) thick paste of drying steps (2) and (3) gained is pulverized, and carries out mixing with the Rhizoma Atractylodis Macrocephalae fine powder of step (1) gained.
6. pharmaceutical composition for the treatment of functional dyspepsia, it is characterized in that by as each described extract of claim 1-5 of active constituents of medicine and pharmaceutically conventional adjuvant formed.
7. pharmaceutical composition according to claim 6 is characterized in that it is a dispersible tablet, calculates by weight, and 337.5 parts of Rhizoma Atractylodis Macrocephalae (parched)s, 225 parts of Fructus Aurantii Immaturuss, 168.75 parts of Radix Bupleuri, 168.75 parts of Fructus Crataegis make 1000 as follows;
(1) gets 1/3 Rhizoma Atractylodis Macrocephalae of measuring and be ground into fine powder;
(2) Fructus Aurantii Immaturus, Fructus Crataegi with 65% ethanol that contains 1% sodium hydroxide as solvent in 25 ℃ ± 2 ℃ lixiviates three times, each 24 hours, merge immersion, to neutral, reclaim ethanol with the hydrochloric acid adjust pH, 1.30～1.35 thick paste when being concentrated into relative density and being 50 ℃;
(3) Fructus Aurantii Immaturus, the medicinal residues of Fructus Crataegi and the Rhizoma Atractylodis Macrocephalae of Radix Bupleuri and surplus after step (2) is extracted decoct with water each 0.5 hour three times, added for the first time behind the water merceration 0.5 hour, with the hydrochloric acid adjust pH to neutral, collecting decoction, filter, 1.20～1.35 clear paste added ethanol when filtrate was concentrated into relative density and is 50 ℃, made to contain the alcohol amount and reach 70%, left standstill 24 hours, the leaching supernatant reclaims ethanol, 1.30～1.35 thick paste when being concentrated into relative density and being 50 ℃;
(4) thick paste of drying steps (2) and (3) gained is pulverized, and carries out mixing with the Rhizoma Atractylodis Macrocephalae fine powder of step (1) gained;
(5) add microcrystalline Cellulose and aspartame in the fine powder behind the mixing of step (4) gained, make granule, drying adds magnesium stearate and low-substituted hydroxypropyl cellulose, is pressed into 1000.
8. pharmaceutical composition according to claim 7, wherein in step (5), weight with respect to the fine powder behind the described mixing, the consumption of microcrystalline Cellulose is 35%～60%, the consumption of low-substituted hydroxypropyl cellulose is 5%～15%, the aspartame consumption is 0.5%～2%, and the magnesium stearate consumption is 0.2%～1%, and amount of water is 10%～35% during the system granule.
9. each described extract of claim 1-5 or each described pharmaceutical composition of claim 6-8 application in preparation treatment functional dyspepsia medicine.
10. the detection method of each described extract of claim 1-5 or each described pharmaceutical composition of claim 6-8, it is characterized in that comprising be selected from following more than one or one:
(1) discriminating of the Rhizoma Atractylodis Macrocephalae: sample extracts with petroleum ether, extract carries out thin layer and differentiates that lamellae is a silica gel g thin-layer plate, and developing solvent is 60～90 ℃ of petroleum ether: ethyl acetate is 17.5: 2.5, developer is 10% ethanol solution of sulfuric acid, with Rhizoma Atractylodis Macrocephalae medical material in contrast;
(2) discriminating of Fructus Aurantii Immaturus: sample extracts with methanol, extract carries out thin layer and differentiates, lamellae is the silica gel g thin-layer plate with the preparation of 0.5% sodium hydroxide, developing solvent is a n-butyl alcohol: glacial acetic acid: water is 4: 1: 5 upper solution, developer is 3% aluminum chloride alcoholic solution, with the Fructus Aurantii Immaturus medical material in contrast; (3) discriminating of Radix Bupleuri: sample extracts with methanol, the water saturated n-butanol extraction of extract, the washing of n-butanol extracting liquid reuse ammonia solution, discard ammoniacal liquor, the saturated water washing of n-butyl alcohol of n-butyl alcohol liquid, discard water liquid, n-butyl alcohol liquid evaporate to dryness, residue adds methanol makes dissolving, as need testing solution, carries out thin layer and differentiates, lamellae is a silica gel g thin-layer plate, developing solvent is a chloroform: methanol: water is lower floor's solution of 7: 3: 1, and developer is the sulfuric acid solution of 2% paradime thylaminobenzaldehyde, with the Radix Bupleuri medical material in contrast;
(4) discriminating of Fructus Crataegi: the samples with water heating extraction, extracting solution adjust pH to 2 is put cold, filter filtering residue oven dry, porphyrize, add diethyl ether merceration 24 hours filters, and filtrate is waved most ether, residue adds dehydrated alcohol makes dissolving, as need testing solution, carries out thin layer and differentiates, lamellae is a silica gel g thin-layer plate, developing solvent is a cyclohexane extraction: acetone: ethyl acetate is 12: 3: 1, and developer is 10% ethanol solution of sulfuric acid, with ursolic acid in contrast;
(5) high effective liquid chromatography for measuring content of hesperidin wherein, is a filler with octadecylsilane chemically bonded silica, with acetonitrile: 0.01% phosphoric acid solution be 18: 82 be mobile phase, the detection wavelength is 283nm, number of theoretical plate calculates by the Hesperidin peak should be not less than 1500.
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| CN101336986B (en) * | 2007-07-06 | 2011-09-28 | 王�锋 | Medicine composition detection method |
| CN104095998A (en) * | 2014-08-01 | 2014-10-15 | 王雪雁 | Traditional Chinese medicine extract with functions of invigorating spleen and harmonizing stomach as well as preparation process and application thereof |
| CN105920112B (en) * | 2016-06-07 | 2019-11-26 | 浙江省中医院 | A kind of Chinese medicine composition and its application |
| CN107260854A (en) * | 2017-06-30 | 2017-10-20 | 山西双人药业有限责任公司 | Zhizhukuanzhong capsule and preparation method thereof |
| CN109596768B (en) * | 2018-12-31 | 2020-03-20 | 海南葫芦娃药业集团股份有限公司 | Detection method of infantile indigestion removing granules |
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| CN1483441A (en) * | 2003-03-12 | 2004-03-24 | 焦智源 | Formula for Weitaihe (stomach medicine) and preparation process thereof |
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Non-Patent Citations (1)
| Title |
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| 枳实消痞散加减治疗功能性消化不良150例分析 张仁有待，中医药临床杂志，第17卷第2期 2005 * |
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Assignee: Zhongshan ZEUS Pharmaceutical Co., Ltd. Assignor: Zhou Zhuohe Contract fulfillment period: 2007.6.2 to 2012.6.1 contract change Contract record no.: 2009440000017 Denomination of invention: Extract for treating functional indigestion and its medicine composition Granted publication date: 20070516 License type: Exclusive license Record date: 20081223 |
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Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2007.6.2 TO 2012.6.1; CHANGE OF CONTRACT Name of requester: ZHONGSHAN CITY ZHONGZHI PHARMACEUTICAL CO., LTD. Effective date: 20081223 |