CN102284041A - Preparation technology and production method of integrated novel Pingwei powder dosage form - Google Patents
Preparation technology and production method of integrated novel Pingwei powder dosage form Download PDFInfo
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Abstract
The invention relates to preparation technology and production method of an integrated novel Pingwei powder dosage form. The integrated novel dosage form comprises the following active ingredients in parts by weight: 120 parts of rhizoma atractylodis, 90 parts of Magnolia officinalis, 60 parts of dried orange peel, 30 parts of radix glycyrrhizae preparata, 2 parts of ginger and 2 parts of Chinese dates. The production process comprises the following steps: supersonic jet milling, extraction in aqueous alcohol, ultrasonic milling and extraction, decoction in water and concentration, nanoscale grinding, high-pressure homogenization, nanoparticle preparation and the like. The preparation technology and production method have the following characteristics and progresses: the advantages of multiple collaboration, multiple targets and the like embodied by utilizing a nano carrier combined technology are emphasized; after large scale production, the production cost can be substantially lowered, the product quality can be substantially improved and the targeting and slow/controlled release properties of medicaments are stronger; the dosage form can be simultaneously administrated internally and externally and can be taken in four time slots respectively according to the midnight-noon ebb-flow and the human blood flow rule; and the dosage form can be prepared into film agents and transdermal agents and then the agents are respectively stuck to different parts of human bodies according to the midnight-noon ebb-flow and the human blood flow rule and can be directly absorbed through skins.
Description
Technical field
The present invention relates to the integrated novel form technology of preparing of a kind of Pingwei San, the invention still further relates to integrated novel form technology of preparing of a kind of Pingwei San and production method thereof.
Background technology
Chinese medicine decocting liquid compound recipe drug effect chemical reaction is too many because of chemical constituent, temporarily also not revealed its mysterious veil, but some mysterious black box drug actions are just ensconced in the Chinese medicine decocting liquid in the Chinese medicinal formulae, can not ask Chinese medicine westernization, the modernization of Chinese medicine simply most and only use monomer and effective site.The Chinese medicine water drug-decocting concentrating liquid could not be given it up! When the Chinese medicinal formulae water decocts, because prescription closes chemical environment complicated in high temperature when frying in shallow oil and the solution, reaction such as complexation, hydrolysis, oxidation, reduction between intrinsic material may take place in solution, thereby some novel substance that did not have originally in the generation solution, these novel substances produce drug actions such as potentiation, attenuation or modification to full side.New component forms the research of mechanism, stability and drug effect thereof in the reinforcement Chinese medicinal formulae decocting liquid, to improving Chinese medicine compound and new drug level, progressively dwindle Chinese medicine compound and new Chinese medicine and international gap, crucial meaning is arranged, also increased new way and new source simultaneously for the research and development new Chinese medicine.
China's drug control relevant laws and regulations regulation changes dosage form and manages as new drug research.The backwardness of preparation level not only influences the performance of curative effect of medication, and cause the medicine added value low, directly influencing the market competition and industrial economy benefit, is to cause China's medical industry product quantity to occupy prostatitis, the world and the output value only is equivalent to the one of the main reasons of one or two transnational drugmaker.
New drug, novel form exploitation level can embody the economy and the technical strength of the medical industry of a country.China's oral formulations accounts for 2/3 of various whole body drug-delivery preparations, and accelerating development and promoting oral sustained-release preparation is the work that current urgent need will be done.
Pingwei San derives from " hospital birdss of the same feather flock together ".The side is made up of for 2 pieces Rhizoma Atractylodis 120 grams, Cortex Magnoliae Officinalis 90 grams, old Pericarpium Citri tangerinae 60 grams, Radix Glycyrrhizae Preparata 30 grams, 2 in Rhizoma Zingiberis Recens, Fructus Jujubae.Smash sieve for loosing.Function: dampness activating the spleen, relieving QI stagnancy in the stomach.Cure mainly the spleen and stomach being stranded by dampness, distension and fullness in the abdomen, anorexia, tastelessness, vomiting is felt sick, and the belch acid regurgitation is often had loose bowels more, heavy, the tiredness with somnolence of limbs, white and greasy fur and thick, moderate pulse.
The pharmacological action of Pingwei San: mainly contain the effects such as aid digestion, antiulcer, antiinflammatory, resisting pathogenic microbes of being good for the stomach.Rhizoma Zingiberis Recens, Pericarpium Citri Reticulatae, Rhizoma Atractylodis, Cortex Magnoliae Officinalis contain armaticity volatile oil and gingerol among the we, and back three flavor medicine sufferings, hardship, oral have gentle stimulation to gastrointestinal mucosa, the secretion of facilitating digestion liquid, increase gastrointestinal motility, and suppress enteral abnormal fermentation, thereby strengthen digestive function, get rid of the enteral pneumatosis, and reach the aid digestion effect that is good for the stomach.Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex Magnoliae Officinalis have obvious inhibitory action to kinds of experiments ulcer model in the side.Rhizoma Zingiberis Recens, Pericarpium Citri Reticulatae, Radix Glycyrrhizae all have obviously inhibitory action to different inflammatory models in the side.Except that Fructus Jujubae, all the other 5 flavor medicines all have resisting pathogenic microbes effect in various degree in the Pingwei San.
The pharmacological action of Rhizoma Atractylodis: potassium atractylate has hypoglycemic activity to mice, rat, rabbit and dog, reduces muscle glycogen and hepatic glycogen simultaneously, suppresses glycogenesis, and oxygen consumption is reduced, and the blood lactic acid content increases.Rhizoma Atractylodis extract can make the obviously blood sugar level reduction of rising of rat through the streptozotocin pre-treatment.Rhizoma Atractylodis have significant inhibitory effect to stress ulcer.Energy shortage, the mucosa resistance that causes because of gastric mucosa blood deficiency, circulatory disturbance weakened, cause tissue necrosis and the ulcer that forms, Rhizoma Atractylodis have positive effect.Rhizoma Atractylodis have the effect that antihistamine stimulates gastric secretion, cause gastroxia and be changed to the ulcer of main cause with mucosa effective to histamine.Rhizoma Atractylodis have remarkable inhibitory action to gastric secretion, the mucosa ulcer that pylorus ligation ulcer, aspirin caused gastric mucosa destruction, the gastric acid surplus that can prevent gastric juice to store causes.The Rhizoma Atractylodis acetone extract can obviously promote gastrointestinal motility.Rhizoma Atractylodis also can suppress the activity of " insufficiency of the spleen " animal intestinal propulsion, and antagonism is had loose bowels; Can reduce serum copper and improve serum zinc, improve " insufficiency of the spleen " animal metabolism function, weight increase, and by improving serum levels of iron, it is synthetic to increase hemoglobin, improves erythrocytic function.Activity all has than the obvious suppression effect to the rabbit duodenum for the alcohol extract of Rhizoma Atractylodis and aqueous solution; The Hepar Mus cytotoxicity that Rhizoma Atractylodis bring out carbon tetrachloride has significant anti-hepatotoxic effect.Atractylodes lancea (Thunb.) DC. is irritated stomach, can significantly increase the drainage of rat sodium and potassium.Experiment in vitro proves that Rhzoma Atractylodis Lanceae volatile oil, eudesmol and hinesol have certain inhibitory action to esophageal cancer cell.
The pharmacological action of Cortex Magnoliae Officinalis: magnolol and iso-agnolol have special and persistent central muscular flaccidity activity.Magnocurarine (magnocurarine) has the striped muscle blocking effect, and the evidence of Bufo siccus motor end plate is because the block nerves impulsion in the transmission of soleplate, makes the motor nerve ending paralysis, causes the paralysis phenomenon of the loose property of whole body motion.The Cortex Magnoliae Officinalis decoct has broad-spectrum antibacterial action, and external all have inhibitory action to staphylococcus aureus, Hemolytic streptococcus, diphtheria corynebacterium, bacillus subtilis, dysentery bacterium, Canis familiaris L. budlet spore tinea bacterium, homocentricity trichophyton, trichophyton, trichophyton etc.; Certain anti-anthrax bacillus effect is arranged in the Cavia porcellus body.In addition, Cortex Magnoliae Officinalis is regulated effects such as smooth muscle, antiulcer, maincenter inhibition, blood pressure lowering, resisting pathogenic microbes, antitumor in addition.
The pharmacological action of Pericarpium Citri Reticulatae: the contained volatile oil of Pericarpium Citri Reticulatae, gastrointestinal tract is had gentle stimulation, but pneumatosis in the intestinal tube is got rid of in the secretion of facilitating digestion liquid, shown that fragrance is good for the stomach and the effectiveness of the wind dispelling therapeutic method to keep the adverse QI flowing downwards.To the experimental gastric ulcer that ligation rat pylorus forms, the subcutaneous injection methylhesperidin can obviously suppress the generation and the development of ulcer, and can suppress gastric secretion.Pericarpium Citri Reticulatae decoct, alcohol extract and hesperidin be the stripped and frog heart on the throne of energy excitement all, and contractility is strengthened, and heart rate is influenced not quite, but the excessive appearance on the contrary of dosage suppresses.Isolated rabbit perfusion Pericarpium Citri Reticulatae decoct coronary artery dilating.The commercially available Pericarpium Citri Reticulatae of the quiet notes of anesthetized dog or rabbit or Citrus chachiensis Hort. C. Suavissima Tanaka decoct or ethanol extract can make blood pressure raise rapidly, and tachyphylaxis does not take place repetitively administered.But more heavy dose of decoct is irritated stomach to dog, does not but have the effect of rising blood pressure.The contained volatile oil of Pericarpium Citri Reticulatae has the zest phlegm-dispelling functions, and sputum is easily brought up, and the main component of bringing into play this effect is limonene and pinene.Bright Pericarpium Citri Reticulatae decoct has dilating effect preferably to the rabbit bronchus.The Pericarpium Citri Reticulatae alcohol extract has than the effect of prednisone relaxation guinea-pig isolated trachea, and to 11 kinds of QI regulating medicine result of the tests of Rutaceae, it is the highest to tire with relievining asthma of Pericarpium Citri Reticulatae, its alcohol extract 0.2g (crude drug)/ml contraction of guinea-pig isolated trachea due to the antagonism histamine fully.Pericarpium Citri Reticulatae also has effects such as immunomodulating, antiinflammatory.
The pharmacological action of Radix Glycyrrhizae: remove that flavonoid glycosides has obvious protective effect to the rat experiment ulcer in the extractum of glycyrrhizin and the Radix Glycyrrhizae.Radix Glycyrrhizae extractum, glycyrrhizin and enoxolone all have promotion sodium to healthy people and animal, the effect of water retention; Low dose of glycyrrhizin (every 100ug) can make rat chest gland atrophy and adrenal gland's weight increase, and produces the effect of glucocorticoid cortisone sample.Then the effect of glucocorticoid sample is not obvious when heavy dose of, only presents the effect of mineralocorticoid sample.Radix Glycyrrhizae extractum and glycyrrhizin all have certain detoxification ability to some drugs poisoning, alimentary toxicosis, interior metabolism product poisoning.The effective ingredient of Detoxication is a glycyrrhizin, detoxification machine is made as glycyrrhizin has adsorption to poisonous substance, glycyrrhizin hydrolyzate glucuronic acid can combine with poisonous substance, and glycyrrhizin have the effect of adrenocortical hormone sample, the result of the aspect combined factors effects such as detoxification ability of enhancing liver.Enoxolone has tangible central antitussive effect, and heavy dose of enoxolone can make mouse breathing suppress.Glycyrrhizin, glycyrrhetate still have anti-inflammatory and antiallergic, anti-liver injury, anti-promoting, antibiotic, anti AIDS virus (glycyrrhizin) effect in addition.
The pharmacological action of Rhizoma Zingiberis Recens: the multiple composition of Rhizoma Zingiberis Recens all has maincenter to suppress, strengthen the effect of tranquilizing soporific and antagonism central stimulants.The ether extract of Rhizoma Zingiberis Recens and water extract all have significant analgesia role.The Rhizoma Zingiberis Recens preserved material can suppress gastric acidity and gastric secretion, and its effect that suppresses stress ulcer is relevant therewith.The ether extract of Rhizoma Zingiberis Recens and water extract all have tangible antiinflammatory action.The Rhizoma Zingiberis Recens ether extract has oxygen lack resistant function, can prolong the time-to-live of normobaric hypoxia and potassium cyanide poisoning anoxia in mice; Gingerade extract and Rhizoma Zingiberis Recens volatile oil are irritated the formation that stomach can obviously prevent the rat experiment thrombosis.Gingerade decocting liquid (10mg/ml) has the clotting time of prolongation and makes the partly soluble effect of fibrin.The Rhizoma Zingiberis Recens preserved material has the obvious suppression effect to the frog vomiting that peripheral emetic copper sulfate brings out; The Rhizoma Zingiberis Recens preserved material can suppress vascular permeability.Gingerol, ginger ketenes have significant molluscicide effect.
Novelty and breakthrough that the present invention has essence are to have found out the key point that Pingwei San modern Chinese medicine novel form Chinese and western medicine theory combines, the present invention will in time fill up both at home and abroad and use " nano-carrier multiple techniques " and researching and developing the blank in " the integrated novel form of Pingwei San " field with theory of integrated Chinese and western medicine, product has the targeting advantage such as wide that distributes, and does not have identical or similar bibliographical information both at home and abroad.Research and development have reached world lead level.Show substantive progressive and novelty of the present invention by international one-level novelty assessment report and patent retrieval.Utilize domestic and international data base to carry out update search, comprehensive domestic and foreign literature is read, analyzing contrast obtains to draw a conclusion: " the integrated novel form of multiple techniques research and development Nano medication " project, its innovative point: 1) adopt the Chinese medicine nano-powder that is rich in trace element, the medicine monomer, effective site, effective part group, Chinese medical concrete, water drug-decocting concentrating liquids etc. go out the nanosphere of different-grain diameter size with the different pharmaceutical preparing carriers, nanocapsule, polymer micelle, solid ester matter nanoparticle, magnetic nano particle, the immune nano grain, nano-emulsion, suspensoid, vesicle, pharmacosomes, microcapsule, nanoparticle, the millimicro ball, millimicro is assisted etc., and mixing is respectively charged into soft then, unite simultaneously in the hard capsule and use and be prepared into a kind of integrated novel form or be prepared into the integrated novel form of other types according to above method; 2) utilization nano-carrier multiple techniques and theory of integrated Chinese and western medicine research and development " the integrated novel form of Nano medication ", product have characteristics such as targeting distributes extensively, slow controlled release properties is strong; Do not see open report at home in the document, these project complex art characteristics have certain novelty and novelty.Science and technology is looked into new numbering: 200921c0704948.
Further: this integrated novel form technology of preparing is to have integrated the advantage separately of the traditional Chinese medical science, doctor trained in Western medicine, with the organic conception of theory of Chinese medical science and collaborative idea and the determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs of paying attention between medicine is the overall strategy tactical thinking, in conjunction with modern western pharmacology, pharmacokinetics, toxicology, pharmaceutics scheduling theory, pay attention to the effectiveness and the therapeutic effect of certified Chinese medicine one matter monomer treatment, pay attention to Chinese medicine active substance, effective site and active substance group the treatment mass action that disease played.Pay attention to the contained trace element of Chinese medicine to the treatment assosting effect that disease played.The effective ingredient of the used Chinese medicine of this Chinese medicine compound is clear and definite, and medicine effect has obtained admitting of modern medicine.Pay attention to utilization nano-carrier multiple techniques development modern Chinese medicine.These will promote the development of China's Chinese medicine industry.
Summary of the invention:
Purpose of the present invention is exactly in order to solve the above-mentioned problems in the prior art, and integrated novel form technology of preparing of a kind of Pingwei San and production method thereof are provided.
Purpose of the present invention is achieved through the following technical solutions:
Integrated novel form technology of preparing of a kind of Pingwei San and production method thereof, wherein: this integrated novel form raw materials of effective components and weight proportion---120 parts of Rhizoma Atractylodis, 90 parts of Cortex Magnoliae Officinalis, 60 parts of old Pericarpium Citri tangerinaes, 30 parts of Radix Glycyrrhizae Preparatas, 2 parts in Rhizoma Zingiberis Recens, 2 parts in Fructus Jujubae.
Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, selenium.Integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof, wherein: medicine is become medicine support material medicine with preparing carriers, crude drug can be one or more combinations in nanoparticle, nanoparticle, micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, the microcapsule etc., and can as required one or more be mixed.Described protection domain is not only the said medicine support material medicine in the described scope, is also included within to prepare on its basis or add the curative effect that other do not influence its disease of controlling, and just makes the pharmaceutical carrier crude drug of its better efficacy.
Further, integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof, wherein: the drug carrier material that this novel form is selected for use, activating agent, help Emulsion, excipient substances such as dispersant are gelatin, albumin, starch and derivant thereof, alginate, beta-schardinger dextrin-, protein, chitosan and derivant thereof, lactose, hydroxypropyl emthylcellulose, ethyl cellulose, cellulose acetate phthalate, the metering system acetate, polylactic acid, cyanoacrylate, the semisolid poe, triglyceride is (as three stearic acid, three Palmic acids, three lauric acids, in three oleic acid etc., the glyceride of long-chain fatty acid), glyceride (as glyceryl monostearate, contains list, two, the synthetic glyceride of triglyceride), cholesterol, Polyethylene Glycol, microcrystalline wax, the whale ester type waxes, erythrocyte, Montmorillonitum, in the tea powder etc. one or more.Described excipient substance is not only the said medicine adjuvant in the described scope, and other do not influence its disease of controlling to be also included within its basic upward interpolation, and just make the excipient substance of its better efficacy.
Further, integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof, wherein: said integrated novel form adopts medicament nano powder body, micro-powder, medicine monomer, effective ingredient, effective site, active substance group, Chinese medical concrete, water drug-decocting concentrating liquid to unite use with different excipient substance, pharmaceutical carrier according to indexs such as the pharmacology of traditional Chinese medical science global theory, compatibility theory and medicine, drug effect, medicine generation, toxicitys.And can mix its one or more according to the preparation needs.
Again further, integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof, wherein: the integrated novel form end product that finally can form is: tablet, powder, suppository, stick, granule, soft capsule, hard capsule, effervescent, drop pill, aerosol, unguentum, oral solution, slow releasing tablet, controlled release tablet.
Integrated novel form technology of preparing of a kind of Pingwei San and production method thereof, it may further comprise the steps:
Step 1: get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, standby.
Step 2: get 30%--90% alcohol-water solution that 60% Rhizoma Atractylodis, Cortex Magnoliae Officinalis, old Pericarpium Citri tangerinae micropowder doubly measure with 6-12 and mix and soaked 1-2 days, reflux, extract, 3 times, extract water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol gets extract with standby.
Step 3: get 60% Radix Glycyrrhizae Preparata, Rhizoma Zingiberis Recens, Fructus Jujubae micropowder, adopt the ultrasonic dispersing extraction equipment of independent research to disperse respectively to extract, ultrasonic power is: 800W-3000W, supersonic frequency: 28KHz--120KHz, to pulverize extraction time be 10-100 minute, extract with standby.
Step 4: with step 2, step 3 gained Chinese medicine extract, adopt the nanon ball-mill of independent research to grind 4-16 hour, get particle size distribution and be the nano powder of 50-1000 nanometer, standby.
Step 5: get each Chinese medicine micropowder of 40%, boiled 3 times with the traditional Chinese medicine extracting machine decocting after being soaked in water two hours, decocting liquid merges and filters, and filtrate concentrates, Chinese medical concrete or water drug-decocting concentrating liquid with standby.
Step 6: with step 2, step 3, step 4 gained Chinese medicine extract, nano powder as required with and the different property of medicine, pharmacological actions, can adopt technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to be prepared respectively, obtain medicine materials such as different medicine monomers, effective site, active substance group.
Step 7: adopt different excipient substances by version in 2010 " preparation part of standards standard and " requirement of version Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " in 2005 in waiting adopts the high pressure breast to spare method respectively in the Chinese pharmacopoeia above-mentioned gained medicine material, inclusion technique, solid state technology, polishing, solvent-fusion method, squeezing and pressing method, complex coacervation, emulsion-crosslinking method, the polymerization dispersion method, fusion method, technology such as freeze-drying are prepared into nanoparticle, nanoparticle, the micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, crude drug such as microcapsule.The crude drug particle diameter is between 10 nanometers-10 micron.
Step 8: " preparation part of standards code requirement in the Chinese pharmacopoeia was got in the crude drug such as step 5 gained Chinese medical concrete or water drug-decocting concentrating liquid and step 7 gained nanoparticle, liposome, nano-emulsion, microcapsule one or more and is mixed by formula proportion by version in 2010.
Step 9: in GMP10000 level toilet, with above-mentioned mixed raw materials medicine adopt the fully-automatic capsule filling machine respectively fill become hard capsule and soft capsule.Also can by version in 2010 " Chinese pharmacopoeia related preparations standard criterion is made the above-mentioned end product of other type.
Step 10: the end product of making is carried out several respectively, bottles, adorns box, seals, pastes labeling, plays exterior and interior packings such as sign indicating number, vanning.Packaged product is transported to the appointed place by production batch and unifies instantaneously sterilising, and opens the sterilization report.
Integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof; wherein: the Chinese medicine of using in described step 1, step 2, the step 3 is pulverized and extracting method; described protection domain is not only described technology of preparing and method; as required, be also included within and add on its basis or use other better effects if, more economical, renewal, breaking method more advanced, more environmental protection, extracting method and technology.
Further, integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof, wherein: crude drug such as the dissimilar nanoparticle that employing different pharmaceutical adjuvant is prepared in the medicine monomer in the described step 6, active substance, effective site technology of preparing and the described step 7, nano-emulsion.The described protection domain of this claim is not only described technology of preparing and method, as required, be also included within add on its basis or use other better effects if, more economical, upgrade, preparation method more advanced, more environmental protection and technology.
Further, integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof, wherein: its key point 1 is different utilization nano-carrier multiple techniques different according to the particle diameter of crude drug and the property of medicine, can produce the gentle controlled capability of different targeting.
Again further, integrated novel form technology of preparing of above-mentioned a kind of Pingwei San and production method thereof, wherein: its key point 2 is to develop simultaneously by interior external administration, can take four time periods respectively by midnight-noon and ebb-flow doctrine, energy and blood of human body flowing law.Also can be prepared into membrane, transdermal agent is attached to the human body different parts respectively by the energy and blood of human body flowing law, can directly absorb by skin.
The outstanding substantive distinguishing features and the obvious improvement of technical solution of the present invention is mainly reflected in:
Novelty and breakthrough that the present invention has essence are to have found out the key point that the Pingwei San Chinese and western medicine theory combines, the present invention will in time fill up both at home and abroad and use " nano-carrier multiple techniques " and researching and developing the blank in " the integrated novel form of Pingwei San " field with theory of integrated Chinese and western medicine, product has the targeting advantage such as wide that distributes, and does not have identical or similar bibliographical information both at home and abroad.Show substantive progressive and novelty of the present invention by international one-level novelty assessment report and patent data library searching.Utilize domestic and international data base to carry out update search, comprehensive domestic and foreign literature is read, analyzing contrast obtains to draw a conclusion: " the integrated novel form of multiple techniques research and development Nano medication " project, its innovative point: 1) adopt the Chinese medicine nano-powder that is rich in trace element, the medicine monomer, effective site, effective part group, Chinese medical concrete, water drug-decocting concentrating liquids etc. go out the nanosphere of different-grain diameter size with the different pharmaceutical preparing carriers, nanocapsule, polymer micelle, solid ester matter nanoparticle, magnetic nano particle, the immune nano grain, nano-emulsion, suspensoid, vesicle, pharmacosomes, microcapsule, nanoparticle, the millimicro ball, millimicro is assisted etc., and mixing is respectively charged into soft then, unite simultaneously in the hard capsule and use and be prepared into a kind of integrated novel form or be prepared into the integrated novel form of other types according to above method; 2) utilization nano-carrier multiple techniques and theory of integrated Chinese and western medicine research and development " the integrated novel form of Nano medication ", product have characteristics such as targeting distributes extensively, slow controlled release properties is strong; Do not see open report at home in the document, these project complex art characteristics have certain novelty and novelty.Science and technology is looked into new numbering: 200921c0704948.
Further, this integrated novel form technology of preparing and production method thereof are to have integrated the advantage separately of the traditional Chinese medical science, doctor trained in Western medicine, with the organic conception of theory of Chinese medical science and collaborative idea and the determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs of paying attention between medicine is the overall strategy tactical thinking, in conjunction with modern western pharmacology, pharmacokinetics, toxicology, pharmaceutics scheduling theory, pay attention to the effectiveness and the therapeutic effect of certified Chinese medicine one matter monomer treatment, pay attention to Chinese medicine active substance, effective site and active substance group the treatment assosting effect that disease played.Pay attention to the contained trace element of Chinese medicine to the treatment assosting effect that disease played.The effective ingredient of the used Chinese medicine of this Chinese medicine compound is clear and definite, and medicine effect has obtained admitting of modern medicine.Pay attention to the different nano-carrier dosage form technologies of preparing of Chinese medicine and unite use.Be to adopt Chinese medicine crude drug nano-powder, monomer, effective site, effective part group, Chinese medicine concentrated extract, water drug-decocting concentrating liquid, nano-medicament carrier etc. to unite use on the compatibility.These various Chinese traditional powder particle diameter major parts of filling a prescription are the granule of 50～1000 nanometers.Adopting different nano-medicament carriers to be prepared into nanoparticle, nanosphere, nanocapsule, solid ester matter nanoparticle, nano-emulsion, vesicle, pharmacosomes, microcapsule, nanoparticle, millimicro ball, millimicro assists etc.Its particle size distribution is between 10 microns of 10 nanometers----.According to difference, the difference and the traditional Chinese medical science monarch theory of slow controlled release time of pharmacology, targeting, reasonable compatibility mixes, and is respectively charged among hard capsule and the soft capsule then.Difference according to the dissolving of capsule material, disintegrate, jitter time can be prepared into targeted systems such as RE targeted system, stomach mucosa absorption system, small intestinal absorption system, colon absorption system respectively.Compare Chinese medicine and medicine monomer, the drug targeting of the overall coordination therapeutical effect of this Chinese medicine compound novel form, slow controlled capability are stronger, and curative effect is more outstanding, and toxic and side effects still less.Multichip carrier and multiple medicines thing monomer etc. are united use, have broken through the traditional monarch compatibility theory of the traditional Chinese medical science, for the modern Chinese medicine development provides a practical effective novel form compatibility program.Be to have substantial technological innovation to break through.
Purpose of the present invention, advantage and characteristics will make an explanation by the non-limitative illustration of following preferred embodiment.These embodiment only are the prominent examples of using technical solution of the present invention, and all technical schemes of taking to be equal to replacement or equivalent transformation and forming all drop within the scope of protection of present invention.
The specific embodiment
Integrated novel form technology of preparing of a kind of Pingwei San and production method thereof, its special feature is: making the raw materials of effective components composition is by weight ratio---120 parts of Rhizoma Atractylodis, 90 parts of Cortex Magnoliae Officinalis, 60 parts of old Pericarpium Citri tangerinaes, 30 parts of Radix Glycyrrhizae Preparatas, 2 parts in Rhizoma Zingiberis Recens, 2 parts in Fructus Jujubae.
Further, play the synergy of standing like the legs of a tripod on the integrated new drug formulation compatibility of Pingwei San of the present invention: 1, prepare nanometer, micro-powder, the bioavailability after strengthening the Pingwei San curative effect and significantly improve prepared slices of Chinese crude drugs cell wall breaking with this with the prepared slices of Chinese crude drugs; 2, with Chinese medicine extract and select suitable pharmaceutical carrier, prepare different Chemistry for Chinese Traditional Medicine monomers, effective ingredient, effective site etc., confirm and strengthen pharmacology, the efficacy of the chemical substance of Pingwei San with this; 3, prepare Chinese medical concrete, water drug-decocting concentrating liquid with the prepared slices of Chinese crude drugs, the temporary transient unpredictable drug effect of bringing with this reaction such as complexation, hydrolysis, oxidation, reduction of strengthening Pingwei San Chinese medicine compound uniqueness also keeps and has strengthened traditional Chinese medical science organic conception, monarch notion.More than three aspects associatings compatibility use, different according to Nano medication particle diameter and character, can reach effects such as many targeting, many collaborative, slow controlled releases, and play useful effect to strengthening the medicine pharmacologically active, effective ingredient pharmacological action effect is significantly higher than conventional formulation.
Production method of the present invention may further comprise the steps:
At first, get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, standby.Getting 30%--90% alcohol-water solution that 60% Rhizoma Atractylodis, Cortex Magnoliae Officinalis, old Pericarpium Citri tangerinae micropowder doubly measure with 6-12 mixes and soaked 1-2 days, reflux, extract, 3 times, extract water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol gets extract with standby.Get 60% Radix Glycyrrhizae Preparata, Rhizoma Zingiberis Recens, Fructus Jujubae micropowder, adopt the ultrasonic dispersing extraction equipment of independent research to disperse respectively to extract, ultrasonic power is: 800W 3000W, supersonic frequency: 28KHz--120KHz, extraction time are 10-100 minute, get extract with standby.With step 2, step 3 gained Chinese medicine extract, adopt the nanon ball-mill of independent research to grind 4-16 hour, get particle size distribution and be the nano powder of 50 nanometers-1000 nanometer, standby.Get each Chinese medicine micropowder of 40% and mix, boiled 3 times with the traditional Chinese medicine extracting machine decocting after being soaked in water two hours, decocting liquid merges and filters, and filtrate concentrates, and gets Chinese medical concrete or water drug-decocting concentrating liquid with standby.With step 2, step 3, step 4 gained Chinese medicine extract, nano powder as required with and the different property of medicine, pharmacological actions, can adopt technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to be prepared respectively, obtain medicine materials such as different medicine monomers, effective site, active substance group.Adopt different excipient substances and carrier by version in 2010 " related preparations part of standards standard and " requirement of version Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " in 2005 in waiting adopts the high pressure breast to spare method respectively in the Chinese pharmacopoeia above-mentioned gained medicine material, inclusion technique, solid state technology, polishing, solvent-fusion method, squeezing and pressing method, complex coacervation, emulsion-crosslinking method, the polymerization dispersion method, fusion method, technology such as freeze-drying are prepared into nanoparticle, nanoparticle, the micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, crude drug such as microcapsule.The crude drug particle size distribution of preparing is between 10 nanometers-10 micron." preparation part of standards code requirement in the Chinese pharmacopoeia was got in the crude drug such as step 5 gained Chinese medical concrete or water drug-decocting concentrating liquid and step 7 gained nanoparticle, liposome, nano-emulsion, microcapsule one or more and is mixed by formula proportion by version in 2010.In GMP10000 level toilet, with above-mentioned mixed raw materials medicine adopt the fully-automatic capsule filling machine respectively fill become hard capsule and soft capsule.Also can make the above-mentioned end product of other type by the related preparations standard criterion.The end product of making is carried out several respectively, bottles, adorns box, seals, pastes labeling, plays exterior and interior packings such as sign indicating number, vanning.Packaged product is transported to the appointed place by production batch and unifies instantaneously sterilising, and opens the sterilization report.
" embodiment one "
Press the following crude drug of preceding method preparation: extractum, nanoparticle, microcapsule, nanoparticle.
It makes the raw materials of effective components composition---120 parts of Rhizoma Atractylodis, 90 parts of Cortex Magnoliae Officinalis, 60 parts of old Pericarpium Citri tangerinaes, 30 parts of Radix Glycyrrhizae Preparatas, 2 parts in Rhizoma Zingiberis Recens, 2 parts in Fructus Jujubae.
Its manufacture process is as follows: in GMP10000 level toilet with extractum, nanoparticle, microcapsule, nanoparticle in 4: 2: 2: after 2 ratios are mixed, adopt a version " preparation part of Chinese pharmacopoeia hard capsule standard in 2010, do not add adjuvant, antiseptic, adopt fully-automatic capsule filling machine fill hard capsule, make hard capsule.Carry out several again, bottle, seal, paste labeling, play exterior and interior packings such as sign indicating number, vanning.Unify instantaneously sterilising by production batch at last, and open the sterilization report.
" embodiment two "
Press the following crude drug of preceding method preparation: water drug-decocting concentrating liquid, nanometer liposome, nano-emulsion, microemulsion.
It makes the raw materials of effective components composition---120 parts of Rhizoma Atractylodis, 90 parts of Cortex Magnoliae Officinalis, 60 parts of old Pericarpium Citri tangerinaes, 30 parts of Radix Glycyrrhizae Preparatas, 2 parts in Rhizoma Zingiberis Recens, 2 parts in Fructus Jujubae.
Its manufacture process is as follows: in GMP10000 level toilet with water drug-decocting concentrating liquid, nanometer liposome, nano-emulsion, microemulsion in 4: 2: 2: after 2 ratios are mixed, adopt a version " preparation part of Chinese pharmacopoeia soft capsule standard in 2010, do not add adjuvant, antiseptic, adopt full-automatic soft capsule filling machine packing soft capsule, make soft capsule.Carry out several again, bottle, seal, paste labeling, play exterior and interior packings such as sign indicating number, vanning.Unify instantaneously sterilising by production batch at last, and open the sterilization report.
" embodiment three "
Press the following crude drug of preceding method preparation: extractum, nanoparticle, nano-emulsion.
It makes the raw materials of effective components composition---120 parts of Rhizoma Atractylodis, 90 parts of Cortex Magnoliae Officinalis, 60 parts of old Pericarpium Citri tangerinaes, 30 parts of Radix Glycyrrhizae Preparatas, 2 parts in Rhizoma Zingiberis Recens, 2 parts in Fructus Jujubae.
Its manufacture process is as follows: after in the GMP10000 level toilet extractum, nanoparticle, nano-emulsion being mixed in 4: 3: 3 ratios, " a preparation part of Chinese pharmacopoeia membrane standard, filmogen adopts polyvinyl alcohol, makes membrane to adopt version in 2010.Adorn box again, seal, paste labeling, play exterior and interior packings such as sign indicating number, vanning.Unify instantaneously sterilising by production batch at last, and open the sterilization report.Every membrane area size is the 2-40 square centimeter, and every medicine film pasted 1272 hours, pasted the medicine position: positions such as neck, chest, back part, abdominal part, shank, foot bottom, Ashi point.
By above-mentioned text description as can be seen: novelty and breakthrough that the present invention has essence are to have found out the key point that Pingwei San Chinese medicine compound Chinese and western medicine theory combines, and the compound compatibility of modern Chinese medicine and technology of preparing can change the pharmacokinetic parameter of medicine monomer, effective ingredient or effective part group.This has proved the scientific meaning of Chinese medicine compound compatibility from the pharmacokinetics level." very just being harmonious; negative and positive intercommunication, coordinating water and fire, precise and tiny circle melt; greatness lies in the capacity " is the elite in the classical works such as Chinese Zhou Yi, Taoism, Huang di's Canon of Medicine, is simple philosophy doctrine thought, also is the research and development thinking and the basic guiding theory of the integrated novel form of this medicine.The traditional Chinese medical science always just has saying of the easy homology of doctor, skill of a doctor homology.This precise and tiny circle of the present invention just melts integration theoretical basis.Among the present invention: monomer, effective site, nanoparticle and carrier etc. be strange, be tiny, be cloudy.Traditional Chinese medical science organic conception, Chinese medical concrete, water drug-decocting concentrating liquid etc. be just, be grand, be the sun.Very just be harmonious then negative and positive intercommunication, the negative and positive intercommunication is then coordinating water and fire, is the optimum balance attitude.Doctor trained in Western medicine research is precise and tiny, and theory of Chinese medical science is that circle melts, and both very just are harmonious, and have just really embodied the organic conception of the combination of Chinese and Western medicine, and " close " is that " integration " is for holding.The tidemark that greatness lies in the capacity, the coordinating water and fire the present invention of being only asked most.This integrated novel form is by the reasonable compatibility of Chinese medicine monomer, effective site, active substance, Chinese medicine active substance group, extractum, water drug-decocting concentrating liquid, prepared slices of Chinese crude drugs nano-particle etc., can produce soft, hard capsule or dosage forms such as nanometer membrane, transdermal agent.Can develop simultaneously, can take four time periods respectively by interior external administration by midnight-noon and ebb-flow doctrine, energy and blood of human body flowing law.Can also do film former to nanometer Chinese medicine, transdermal agent is attached to the human body different parts, can directly absorb by skin.
See that further the various Chinese medicine particle diameter major parts that the present invention prepares are the granule of 50～1000 nanometers.Adopt different nano-medicament carriers and technology can be prepared into nanoparticle, nanosphere, solid ester plastid, nano-emulsion, pharmacosomes, microgranule, millimicro ball, little assist etc.Its particle size distribution is between 10 microns of 10 nanometers----.According to difference, the difference and the traditional Chinese medical science monarch theory of slow controlled release time of medicine pharmacology, targeting, reasonable compatibility mixes, and can be respectively charged among hard capsule and the soft capsule then.Difference according to the dissolving of capsule material, disintegrate, jitter time can be prepared into targeted systems such as RE targeted system, stomach mucosa absorption system, small intestinal absorption system, colon absorption system respectively.Compare Chinese medicine and medicine monomer or Western medicine, overall coordination therapeutical effect of this integrated novel form and drug targeting, slow controlled capability are stronger, and curative effect is more outstanding, and toxic and side effects still less.Having broken through the traditional monarch compatibility theory of the traditional Chinese medical science, is the innovation and the model of Chinese medicine tradition compatibility theory and traditional Chinese medical science pharmaceutics, for the preparation of Pingwei San modern Chinese medicine and production have proposed a practical effective novel form compatibility program.Be to have substantial preparation consolidation and innovation and technological break-through.
Claims (10)
1. integrated novel form technology of preparing of Pingwei San and production method thereof is characterized in that: 120 parts of this novel form raw materials of effective components and weight proportion---Rhizoma Atractylodis, 90 parts of Cortex Magnoliae Officinalis, 60 parts of old Pericarpium Citri tangerinaes, 30 parts of Radix Glycyrrhizae Preparatas, 2 parts in Rhizoma Zingiberis Recens, 2 parts in Fructus Jujubae.
Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, selenium.
2. integrated novel form technology of preparing of a kind of Pingwei San according to claim 1 and production method thereof, it is characterized in that: medicine is become medicine support material medicine with preparing carriers, crude drug can be one or more combinations in nanoparticle, nanoparticle, micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, the microcapsule etc., and can as required one or more be mixed.The described protection domain of this claim is not only the said medicine support material medicine in the described scope, is also included within to prepare on its basis or add the curative effect that other do not influence its disease of controlling, and just makes the pharmaceutical carrier crude drug of its better efficacy.
3. according to claim 1, integrated novel form technology of preparing of 2 described a kind of Pingwei Sans and production method thereof, it is characterized in that: the drug carrier material that this novel form is selected for use, activating agent, help Emulsion, excipient substances such as dispersant are gelatin, albumin, starch and derivant thereof, alginate, beta-schardinger dextrin-, protein, chitosan and derivant thereof, lactose, hydroxypropyl emthylcellulose, ethyl cellulose, cellulose acetate phthalate, the metering system acetate, polylactic acid, cyanoacrylate, the semisolid poe, triglyceride is (as three stearic acid, three Palmic acids, three lauric acids, in three oleic acid etc., the glyceride of long-chain fatty acid), glyceride (as glyceryl monostearate, contains list, two, the synthetic glyceride of triglyceride), cholesterol, Polyethylene Glycol, microcrystalline wax, the whale ester type waxes, erythrocyte, Montmorillonitum, in the tea powder etc. one or more.The described protection domain of this claim is not only the said medicine adjuvant in the described scope, and other do not influence its disease of controlling to be also included within its basic upward interpolation, and just make the excipient substance of its better efficacy.
4. according to claim 1 or 2 or 3 any integrated novel form technology of preparing of described a kind of Pingwei San and production methods thereof, it is characterized in that: said integrated novel form adopts medicament nano powder body, micro-powder, medicine monomer, effective ingredient, effective site, active substance group, Chinese medical concrete, water drug-decocting concentrating liquid to unite use with different excipient substance, pharmaceutical carrier according to indexs such as the pharmacology of traditional Chinese medical science global theory, compatibility theory and medicine, drug effect, medicine generation, toxicitys.And can mix its one or more according to the preparation needs.
5. according to claim 1 or 2 or 3 or 4 any integrated novel form technology of preparing of described a kind of Pingwei San and production methods thereof, it is characterized in that: the integrated novel form end product that finally can form is: tablet, powder, suppository, stick, granule, soft capsule, hard capsule, effervescent, drop pill, aerosol, unguentum, oral solution, slow releasing tablet, controlled release tablet.
6. integrated novel form technology of preparing of Pingwei San and production method thereof is characterized in that may further comprise the steps:
Step 1: get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, standby.
Step 2: get 30%--90% alcohol-water solution that 60% Rhizoma Atractylodis, Cortex Magnoliae Officinalis, old Pericarpium Citri tangerinae micropowder doubly measure with 6-12 and mix and soaked 1-2 days, reflux, extract, 3 times, extract water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol gets extract with standby.
Step 3: get 60% Radix Glycyrrhizae Preparata, Rhizoma Zingiberis Recens, Fructus Jujubae micropowder, adopt the ultrasonic dispersing extraction equipment of independent research to disperse respectively to extract, ultrasonic power is: 800W-3000W, supersonic frequency: 28KHz--120KHz, extraction time are 10-100 minute, get extract with standby.
Step 4: with step 2, step 3 gained Chinese medicine extract, adopt the nanon ball-mill of independent research to grind 4-16 hour, get particle size distribution and be the nano powder of 50-1000 nanometer, standby.
Step 5: get each Chinese medicine micropowder of 40%, boiled 3 times with the traditional Chinese medicine extracting machine decocting after being soaked in water two hours, decocting liquid merges and filters, and filtrate concentrates, extractum or water drug-decocting concentrating liquid with standby.
Step 6: with step 2, step 3, step 4 gained Chinese medicine extract, nano powder as required with and the different property of medicine, pharmacological actions, can adopt technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to be prepared respectively, obtain medicine materials such as different medicine monomers, effective site, active substance group.
Step 7: adopt different excipient substances and carrier by version in 2010 " related preparations part of standards standard and " requirement of version Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " in 2005 in waiting adopts the high pressure breast to spare method respectively in the Chinese pharmacopoeia above-mentioned gained medicine material, inclusion technique, solid state technology, polishing, solvent-fusion method, squeezing and pressing method, complex coacervation, emulsion-crosslinking method, the polymerization dispersion method, fusion method, technology such as freeze-drying are prepared into nanoparticle, nanoparticle, the micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, crude drug such as microcapsule.The crude drug particle diameter is between 10 nanometers-10 micron.
Step 8: " preparation part of standards code requirement in the Chinese pharmacopoeia was got in the crude drug such as step 5 gained Chinese medical concrete or water drug-decocting concentrating liquid and step 7 gained nanoparticle, liposome, nano-emulsion, microcapsule one or more and is mixed by formula proportion by version in 2010.
Step 9: in GMP10000 level toilet, with above-mentioned mixed raw materials medicine adopt the fully-automatic capsule filling machine respectively fill become hard capsule and soft capsule.Also can by version in 2010 " Chinese pharmacopoeia related preparations standard criterion is made the above-mentioned end product of other type.
Step 10: the end product of making is carried out several respectively, bottles, adorns box, seals, pastes labeling, plays exterior and interior packings such as sign indicating number, vanning.Packaged product is transported to the appointed place by production batch and unifies instantaneously sterilising, and opens the sterilization report.
7. integrated novel form technology of preparing of a kind of Pingwei San according to claim 6 and production method thereof; it is characterized in that: pulverizing of using in described step 1, step 2, the step 3 and extracting method; the described protection domain of this claim is not only described technology of preparing and method; as required, be also included within and add on its basis or use other better effects if, more economical, renewal, breaking method more advanced, more environmental protection, extracting method and technology.
8. integrated novel form technology of preparing of a kind of Pingwei San according to claim 7 and production method thereof; it is characterized in that: crude drug such as the dissimilar nanoparticle that employing different pharmaceutical adjuvant is prepared in the medicine monomer in the described step 6, active substance, effective site technology of preparing and the described step 7, nano-emulsion; the described protection domain of this claim is not only described technology of preparing and method; as required, be also included within add on its basis or use other better effects if, more economical, upgrade, preparation method more advanced, more environmental protection and technology.
9. integrated novel form technology of preparing of a kind of Pingwei San according to claim 8 and production method thereof, it is characterized in that: its key point 1 is different utilization nano-carrier multiple techniques different according to the particle diameter of crude drug and the property of medicine, can produce the gentle controlled capability of different targeting.
10. integrated novel form technology of preparing of a kind of Pingwei San according to claim 9 and production method thereof is characterized in that: its key point 2 is to develop simultaneously by interior external administration, can take four time periods respectively by midnight-noon and ebb-flow doctrine, energy and blood of human body flowing law.Also can be prepared into membrane, transdermal agent is attached to the human body different parts respectively by the energy and blood of human body flowing law, can directly absorb by skin.
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| CN102772771A (en) * | 2012-07-28 | 2012-11-14 | 李承平 | Medicine capsules for treating spleen and stomach wet hysteresis |
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| CN103393807A (en) * | 2013-08-13 | 2013-11-20 | 成都中医药大学 | Medicine composition for treating gastrointestinal disease, preparation method and use |
| CN104971325A (en) * | 2015-06-15 | 2015-10-14 | 兰州大学应用技术研究院有限责任公司 | Spleen reinforcing and stomach harmonizing traditional Chinese medicinal composition and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102552795A (en) * | 2012-03-09 | 2012-07-11 | 通化斯威药业股份有限公司 | Drug capable of increasing gastric motility and treating chronic gastritis and preparation method thereof |
| CN102772771A (en) * | 2012-07-28 | 2012-11-14 | 李承平 | Medicine capsules for treating spleen and stomach wet hysteresis |
| CN103146554A (en) * | 2013-03-08 | 2013-06-12 | 马胜清 | Red date liquorice liquor |
| CN103393807A (en) * | 2013-08-13 | 2013-11-20 | 成都中医药大学 | Medicine composition for treating gastrointestinal disease, preparation method and use |
| CN103393807B (en) * | 2013-08-13 | 2015-12-02 | 成都中医药大学 | A kind of treat gastrointestinal disease pharmaceutical composition and preparation method and purposes |
| CN104971325A (en) * | 2015-06-15 | 2015-10-14 | 兰州大学应用技术研究院有限责任公司 | Spleen reinforcing and stomach harmonizing traditional Chinese medicinal composition and preparation method thereof |
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