CN102284045A - Banxia Houpo Tang integrated novel dosage form preparation technology and production method thereof - Google Patents
Banxia Houpo Tang integrated novel dosage form preparation technology and production method thereof Download PDFInfo
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Abstract
The invention relates to Banxia Houpo Tang integrated novel dosage form preparation technology and a production method thereof. TheBanxia Houpo Tang integrated novel dosage form contains the following raw materials by weight portions: 12 portions of Banxia, 9 portions of Houpo, 12 portions of tackahoe, 9 portions of gingers and 6 portions of folium. The production process includes the following steps of pulverization by ultrasonic airflow, extraction by alcohol water, pulverization and extraction by ultrasonic wave, concentration by decocting, drying by ultrasonic sprayer, nanometer grinding, high-pressure homogenization, nano-grain preparation and the like. The preparation technology has the advantages of nanometer carrier coupling technique such as multiple cooperations, multiple targets and the like. After the mass production is realized, the production cost can be greatly reduced, the product quality can be greatly improved, and the targeting and the slow release property of the medicine are stronger. The medicine can be taken orally or used externally and can be taken in four periods of time according to the midnight-noon ebb-flow and the blood circulation principle of the human body. The medicine also can be prepared into a membrane form and a transdermal agent to be respectively adhered onto different parts of the human body according to the midnight-noon ebb-flow and the blood circulation principle of the human body and can be directly absorbed by the skin.
Description
Technical field
The present invention relates to the integrated novel form technology of preparing of a kind of BANXIA HOUPU TANG, the invention still further relates to integrated novel form technology of preparing of a kind of BANXIA HOUPU TANG 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.BANXIA HOUPU TANG is derived from Han dynasty Zhang Zhongjing " Medical Treasures of the Golden Chamber ", and is square by the Rhizoma Pinelliae, Cortex Magnoliae Officinalis, and Poria, Rhizoma Zingiberis Recens, Folium Perillae is formed.Function: promoting QI to circulate and dispersing the agglomeration of the pathogens, lowering the adverse-rising QI and eliminating phlegm.Cure mainly globus hystericus, stagnation of QI causing phlegm retention if any thing resistance, is coughed up and can not told in the pharynx, can swallow any more, and chest and diaphragm is full vexed, or coughs or vomit, and tongue fur is white and moist or white greasy, the slow or stringy and rolling pulse of stringy pulse.Modern times are usually used in treating diseases such as hysteria, stomach neurosis, chronic pharyngitis, chronic bronchitis, esohagismus.
The pharmacological action of BANXIA HOUPU TANG: mainly contain calmness, antiallergic is pressed down the emesis of vomitting, and promotes effects such as function of intestinal canal.BANXIA HOUPU TANG 4g/kg took for mice continuously 6, can significantly suppress autonomic movement, and more apparent in dark active stage effect especially, this effect is sustainable two days after the drug withdrawal; But, illustrate that we have significant sedation with 2g/kg and 4g/kg dosage significant prolongation cyclobarbital induced mice righting reflex loss time also.BANXIA HOUPU TANG has remarkable inhibitory action to the Cavia porcellus passive cutaneous anaphylaxis, PCA, and to 2,4-dinitro-chloro-benzene induced mice delayed hypersensitivity also has inhibitory action, and we are described, and anaphylaxis has the activity of inhibition to I type familial combined hyperlipidemia.Cortex Magnoliae Officinalis and Folium Perillae tool physiologically active in the side are if full side removes Folium Perillae. and inhibitory action obviously descends.The volatility main component perillaldehyde of Folium Perillae also has remarkable inhibitory action to type anaphylaxis of Cavia porcellus I and the allergy of mice IV type.The experiment of anesthetized cat shows that quiet notes 400mg/kg BANXIA HOUPU TANG can significantly suppress the laryngeal reflex of electricity irritation superior laryngeal nerve, and effect was kept 20-30 minute.Form in the flavour of a drug, Folium Perillae (120mg/kg), Cortex Magnoliae Officinalis (140mg/kg) also can suppress laryngeal reflex due to the electricity irritation, and its excess-three flavor does not then have this effect.BANXIA HOUPU TANG can be improved water stress rats stomach and gather venular blood circulation.
The pharmacological action of the Rhizoma Pinelliae: Rhizoma Pinelliae, Rhizoma Pinelliae (processed with Rhizoma Zingiberis Recens), Rhizoma Zingiberis Recens are soaked the decoct of the Rhizoma Pinelliae and the Alumen Rhizoma Pinelliae, 0.6-1g/kgig or iv, cough due to cat iodine liquid injection thoracic cavity or the electricity irritation superior laryngeal nerve there is tangible antitussive effect, Rhizoma Pinelliae preparation has significant inhibitory effect to the salivation that pilocarpine causes, the vomiting that the Rhizoma Pinelliae causes Apomorphinum, Folium Digitalis Purpureae, copper sulfate all has certain town to tell effect.Pinellin 1.25mg/ml (in 0.9%NaCl) sc0.2ml is 50% to the pregnant rate that presses down of early pregnancy mice.Rhizoma Pinelliae trypsin inhibitor only suppresses trypsin to amide, ester, hemoglobin and caseic hydrolysis, can not suppress chymase, bradykinin is released a piece enzyme, subtilisin and papain to the hydrolysis of substrate separately.From the scope of chemical molecular size, Rhizoma Pinelliae trypsin inhibitor should belong to the macromole inhibitor.During Rhizoma Pinelliae decocting liquid 200% concentration 26.5ml/kg prevention administration, the rat ventricular arrhythmia that barium chloride is brought out has tangible antagonism (P＜0.05).Rhizoma Pinelliae extractum is inhibitory action to the exsomatize heart and Cor Leporis.Pinellin also is a kind of phytohemagglutinin, and it and rabbit erythrocyte have single-minded hemagglutinative vigor, and concentration is low to moderate every 1ml2 μ g and still has agglutination.Pinellin be at present known unique with mannose not with the bonded a kind of protein of glucose with agglutinin effect.
The pharmacological action of Cortex Magnoliae Officinalis: magnolol and iso-agnolol have special and persistent central muscular flaccidity activity. and magnocurarine (magnocurarine) has the striped muscle blocking effect, the evidence of Bufo siccus motor end plate is because block nerves is got excited in the transmission of soleplate, make the motor nerve ending paralysis, causing the paralysis phenomenon of the loose property of whole body motion. the Cortex Magnoliae Officinalis decoct has broad-spectrum antibacterial action, and is external to staphylococcus aureus, Hemolytic streptococcus, diphtheria corynebacterium, bacillus subtilis, dysentery bacterium, Canis familiaris L. budlet spore tinea bacterium, the homocentricity trichophyton, trichophyton, trichophyton etc. all have inhibitory action; 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 Poria: pachyman (PPS), the tool anti-tumor activity. carboxymethyl pachymose tool immunological enhancement and antitumor action .25% Poria alcohol preserved material are given normal rabbit lumbar injection 0.5g/Kg, diuresis appears. proves with adrenalectomized rat experiment, diuresis is relevant with the absorption that influences renal tubules Na+. and pachymaran has inhibitory action to murine sarcoma S180, suppression ratio reaches 96.88%. and cultivates in the Poria mycelium that obtains from artificial deep layer, can extract pachyman F1 and H11, the obvious anti-tumor activity of tool. pachyman has potentiation to the immunologic function of normal and tumor-bearing mice, can strengthen macrophage phagocytosis of mice. Poria water, ethanol, ether extract all has the contraction of enhancing to isolated frog heart, accelerate heart rate function. decoct is Poria cum Radix Pini's injection particularly, and animal is had sedation.
The pharmacological action of Folium Perillae: the rabbit with Folium Perillae decoct and the heating of preserved material 2g/kg oral administration typhoid fever polyvalent vaccine has faint refrigeration function.Folium Perillae can suppress aureus growth in vitro.Folium Perillae extractum is 200-1600mg/ml to 6 kinds of mycobiotic agar culture minimum inhibitory concentrations (MIC); Perillaldehyde in the extractum plays main bacteriostasis.It is oral that perilla oil 0.35ml/kg gives rabbit; Blood glucose is risen; After main component perillaldehyde in the oil was made oxime (Oxime), the blood glucose increasing effect was stronger than perilla oil.Folium Perillae water extract can shorten blood clotting time, blood plasma recalcification time and activated partial thromboplastin time to the intravenous injection of tame rabbit ear table, illustrates that the Folium Perillae intrinsic coagulation system has facilitation, and also not obvious to the influence of extrinsic coagulation system.Isolated Perilla ketone from Folium Perillae has the enterokinesia of promotion effect to rat, and the enteral prods motion is quickened, and this is because Perill ketone expands about flesh to intestinal stimulation to be arranged.Isolated perillaldehyde, Stigmasterol, Dill apiole all have sedation from Folium Perillae, can prolong the length of one's sleep of the rat of phenobarbital minimizing, wherein median effective dose=1.57mg/kg of Dill apiole.1: 20 concentration of Folium Perillae water decoction has inhibitory action to viral ECHO11 strain.
Rhizoma Zingiberis Recens is the active drug of treatment hydrochloric acid-ethanol ulcer, and its effective ingredient is a zingiberene, has the effect of protection Gastric Mucosal Cells.In fragrance is good for the stomach crude drug, particularly contain terpenoid derived essential oils such as zingiberene in the zingiberaceous plant more, be one of the effective ingredient of crude drug that is good for the stomach.The Rhizoma Zingiberis Recens decoct is the two-way function that suppresses with excited to the secretion of dog gastric acid and gastric juice, suppresses in initial a few hours, then continues with the excitement of long period later on.Rhizoma Zingiberis Recens can make the pepsin effect weaken, and the effect of lipolytic enzyme strengthens.But the amylase in the Rhizoma Zingiberis Recens heavy damage pancreatin makes pancreatin significantly descend to the Digestion of starch.Also can suppress the beta amylase in the amylase, hinder starch saccharification.The water extract of Rhizoma Zingiberis Recens has significant absorption facilitation, strengthens its bioavailability, gives full play to curative effect.Experiment shows: oil of Rhizoma Zingiberis Recens has therapeutical effect to rat carbon tetrachloride liver damage, and serum SGPT is reduced; The mouse carbon tetrachloride liver damage there is preventive effect, and can reduces BSP retention amount.The shogaol extract has excitation to anesthetized cat vasomotor center and respiratory center, and heart is also had direct excitation.The water extract of Rhizoma Zingiberis Recens can significantly reduce the amount that human blood platelets labelling arachidonic acid (AA) generates TXB 2 and PGS, reduces the formation of the peroxide in the PG, and the effect of strong inhibition platelet aggregation is arranged.Ginger extract all has obvious inhibitory action to staphylococcus aureus, Staphylococcus albus, Bacillus typhi, bacterium sonnei, bacillus pyocyaneus, and its effect is dependence with concentration.Especially the inhibitory action with staphylococcus aureus and Staphylococcus albus is the strongest.The Rhizoma Zingiberis Recens Wheat Protein.Rhizoma Zingiberis Recens extract also can suppress oxygen production and linoleic oxidation.
Novelty and breakthrough that the present invention has essence are to have found out the key point that BANXIA HOUPU TANG 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 BANXIA HOUPU TANG " 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG and production method thereof, wherein: this integrated novel form raw materials of effective components and weight proportion---
12 parts of the Rhizoma Pinelliaes, 9 parts of Cortex Magnoliae Officinalis, 12 parts in Poria, 9 parts in Rhizoma Zingiberis Recens, 6 parts of Folium Perillae.
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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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% the Rhizoma Pinelliae, Cortex Magnoliae Officinalis, Poria 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% Rhizoma Zingiberis Recens, Folium Perillae micropowder, adopt the ultrasonic dispersing pulverizing 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, Chinese medicine 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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, 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 made 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG " 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.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 BANXIA HOUPU TANG and production method thereof, its special feature is: making the raw materials of effective components composition is by weight ratio---
12 parts of the Rhizoma Pinelliaes, 9 parts of Cortex Magnoliae Officinalis, 12 parts in Poria, 9 parts in Rhizoma Zingiberis Recens, 6 parts of Folium Perillae.
Further, play the synergy of standing like the legs of a tripod on the integrated new drug formulation compatibility of BANXIA HOUPU TANG of the present invention: 1, prepare nanometer, micro-powder, the bioavailability after strengthening the BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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, gets each prepared slices of Chinese crude drugs pretreatment, inserts 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, and standby.Get 30%--90% alcohol-water solution that 60% the Rhizoma Pinelliae, Cortex Magnoliae Officinalis, Poria micropowder doubly measure with 6-12 and mix and soaked 1-2 days, reflux, extract, 3 times is extracted water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol, extract with standby.Get 60% Rhizoma Zingiberis Recens, Folium Perillae micropowder, adopt the ultrasonic dispersing pulverizing 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, Chinese medicine 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---
12 parts of the Rhizoma Pinelliaes, 9 parts of Cortex Magnoliae Officinalis, 12 parts in Poria, 9 parts in Rhizoma Zingiberis Recens, 6 parts of Folium Perillae.
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---
12 parts of the Rhizoma Pinelliaes, 9 parts of Cortex Magnoliae Officinalis, 12 parts in Poria, 9 parts in Rhizoma Zingiberis Recens, 6 parts of Folium Perillae.
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---
12 parts of the Rhizoma Pinelliaes, 9 parts of Cortex Magnoliae Officinalis, 12 parts in Poria, 9 parts in Rhizoma Zingiberis Recens, 6 parts of Folium Perillae.
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 12-72 hour, 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG and production method thereof is characterized in that: this novel form raw materials of effective components and weight proportion---
12 parts of the Rhizoma Pinelliaes, 9 parts of Cortex Magnoliae Officinalis, 12 parts in Poria, 9 parts in Rhizoma Zingiberis Recens, 6 parts of Folium Perillae.
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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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% the Rhizoma Pinelliae, Cortex Magnoliae Officinalis, Poria 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% Rhizoma Zingiberis Recens, Folium Perillae micropowder, adopt the ultrasonic dispersing pulverizing 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 BANXIA HOUPU TANG 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 BANXIA HOUPU TANG according to claim 7 and production method thereof; it is characterized in that: the medicine monomer in the described step 6; active substance; the dissimilar nanoparticle that adopts the different pharmaceutical adjuvant to be prepared in effective site technology of preparing and the described step 7; crude drug such as nano-emulsion; 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; upgrade; more advanced; the more preparation method of environmental protection and technology.
9. integrated novel form technology of preparing of a kind of BANXIA HOUPU TANG 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 BANXIA HOUPU TANG 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 made 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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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106138541A (en) * | 2015-03-13 | 2016-11-23 | 信阳农林学院 | The fresh Rhizoma Pinelliae processing technique processed in a kind of place of production |
| CN106390065A (en) * | 2016-10-26 | 2017-02-15 | 北京大品种联盟科技咨询有限公司 | Application of traditional Chinese medicine preparation in treating and/or preventing laryngo-pharyngeal reflux |
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2010
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106138541A (en) * | 2015-03-13 | 2016-11-23 | 信阳农林学院 | The fresh Rhizoma Pinelliae processing technique processed in a kind of place of production |
| CN106138541B (en) * | 2015-03-13 | 2021-04-16 | 信阳农林学院 | Processing technology of fresh rhizoma pinelliae preparata in producing area |
| CN106390065A (en) * | 2016-10-26 | 2017-02-15 | 北京大品种联盟科技咨询有限公司 | Application of traditional Chinese medicine preparation in treating and/or preventing laryngo-pharyngeal reflux |
| CN106390065B (en) * | 2016-10-26 | 2018-03-23 | 北京大品种联盟科技咨询有限公司 | Purposes of the pinellia tuber and magnolia bark Chinese medicine preparation in treatment and/or prevention reflux sphagitis medicine is prepared |
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