CN102283961A - Preparation technology and production method for novel integrated dosage form of lenitive pill - Google Patents

Abstract

The invention relates to a preparation technology and production method for a novel integrated dosage form of lenitive pill. The novel integrated dosage form comprises the following raw materials containing effective ingredients: 18 parts by weight of hawthorn, 6 parts by weight of medicated leaven, 9 parts by weight of Pinellia ternata, 9 parts by weight of Poria cocos, 3 parts by weight of dried tangerine or orange peel, 3 parts by weight of fructus forsythia and 3 parts by weight of semen raphani. The production method comprises the steps including supersonic airflow pulverizing, alcohol water extraction, ultrasonic crushing extraction, water frying concentration, nano-grinding, high-pressure homogenizing, nano-particle preparation and the like. According to the novel integrated dosage form disclosed by the invention, the advantages, such as multi-cooperation, multi-targeting and the like, are embodied by utilizing a nano-carrier joint application technology; after the scale production is realized, the production cost can be greatly reduced; the product quality can be greatly increased; the targeting property and the slow controlled release property of drugs are stronger; internal and external drug deliveries can be realized at the same time; the drugs can be taken respectively during four time periods according to meridional lingers and a human blood flow law; the drugs can also be prepared into film agents and transdermal agents which can be respectively pasted on different positions of human bodies according to the meridional lingers and the human blood flow law; and the drugs can be directly absorbed through skin.

Description

Integrated novel form technology of preparing of a kind of lenitive pill and production method thereof

Technical field

The present invention relates to the integrated novel form technology of preparing of a kind of lenitive pill, the invention still further relates to integrated novel form technology of preparing of a kind of lenitive pill 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.

The lenitive pill prescription derives from " danxi's experiential therapy ".Square by 6 liang of Fructus Crataegis, 2 liang of Massa Medicata Fermentata, 3 liang of the Rhizoma Pinelliaes, 3 liang in Poria, 1 liang of Pericarpium Citri Reticulatae, 1 liang of Fructus Forsythiae, 1 liang of medicine of Semen Raphani is formed.Go up to last, steamed cake is a ball, and is big as Semen Firmianae.Prescription effect dyspepsia and intestinal stasis relieving stomach function regulating.Prescription cures mainly food stagnation and stagnates, the chest and diaphragm feeling of fullness, and abdominal distention stomachache, belching and acid regurgitation, the anorexia vomiting and nausea, or food stagnation addiction piece is arranged in the abdomen, or stool lets out dysentery.The excessive taste that injure of invalid diet, the dyspepsia gastrointestinal, mechanism of qi is hindered, so abdominal distention; Stomach-QI being unable to descend normally is told so dislike vomiting due to improper diet; Down under the pressure of intestinal, so loose stool and diarrhea.Fructus Crataegi disappears carnivorous greasy long-pendingly in the side, and the Massa Medicata Fermentata food and drink is old long-pending; Semen Raphani rapid digestion of food face mental disorder is long-pending; Rhizoma Pinelliae Preparata, Pericarpium Citri Reticulatae promoting qi circulation, resolving food retention preventing or arresting vomiting; Poria spleen invigorating eliminating dampness by diuresis antidiarrheal; Fructus Forsythiae heat clearing away eliminating stagnation.

The pharmacological action of Fructus Crataegi: the effect that Fructus Crataegi has to be increased myocardial contraction, increase cardiac output, decreased heart rate.Experimental results show that: Fructus Crataegi has persistent hypotensive effect.It is for oral administration that Fructus Crataegi is made syrup, and tangible hypotensive effect is arranged.The different various hyperlipidemia models that partly different animals caused that extract of Fructus Crataegi have more sure effect for reducing fat.Experiment shows: the Fructus Pyri Pashiae aqueous extract can significantly reduce serum total cholesterol content, and it acts on significantly greater than pantethin.Clinically make tablet, treatment hypertriglyceridemia 75 examples, effective percentage 81% with Fructus Crataegi extract.Can increase enzyme in the stomach, facilitating digestion after Fructus Crataegi is for oral administration; Wherein contained lipase also can promote the digestion of fatty food stagnation.Fructus Crataegi in will he, Fu Shi, the Song, this close dysentery bacterium has stronger antibacterial action; Bacillus pyocyaneus, staphylococcus aureus, escherichia coli, Bacillus proteus, anthrax bacillus, group B streptococcus, diphtheria corynebacterium, Bacillus typhi etc. all there is antibacterial action.The stem and leaf of Fructus Crataegi also has stronger antibacterial action to staphylococcus aureus, anthrax bacillus.The concocting method difference does not have obvious influence to the antibacterial action of Fructus Crataegi, and Fructus Crataegi and Fructus Crataegi (parched to brown) do not have significant difference to Fu Shi, bacterium sonnei, Bacillus proteus, colibacillary effect.Fructus Crataegi has the effect of shrinking the uterus.Because uterine contraction can make the interior clot of uterine cavity be easy to discharge, and helps the uterine involution in puerperal.In addition, Fructus Crataegi energy blood vessel dilating, releasing congestion state and Fructus Crataegi have certain sedation, so puerperal abdonimal pain, menstrual pain are had analgesic effect.The Fructus Crataegi aqueous extract has the effect of removing free radical, and its ability and dosage of removing free radical has tangible dose-effect relationship; Depolymerization has protective effect to the free yl induction hyaluronic acid; And hepatoprotective effect is arranged, can obviously suppress the effect of chronic alcoholism model mice liver activity of adenosine deaminase.Fructus Crataegi has the effect of remarkable enhancing humoral immunization and cellular immune function.Folium Crataegi extractum has gentleness, slow and persistent diuresis, and is less to electrolytical influence during diuresis.Under the Gastric pH condition, hawthorn extract can be eliminated the prerequisite material of synthetic nitrosamine, can blocking nitrosamine formation synthetic, certain protective effect on cancer risk is arranged.Fructus Crataegi also has expelling tenia and spasmolytic, sedation.

The pharmacological action of Massa Medicata Fermentata: the main component of Massa Medicata Fermentata contains yeast, amylase, volatile oil, glycoside, fatty oil and vitamin B etc.Still contain enzyme, ergosterol, protein etc.According to this product ingredient, can be by the formation of coenzyme being brought into play influence to substance metabolism; And, promote human body to proteinic digestion, absorption and utilization in the food by the oxidation energy supply.

The pharmacological action of the Rhizoma Pinelliae: Rhizoma Pinelliae Preparata has the town to tell effect, and Rhizoma Pinelliae then has emetic action, illustrates that emetic the telling with the town of the Rhizoma Pinelliae belongs to respectively due to two kinds of heterogeneities.Tell in Rhizoma Pinelliae town may be relevant with the inhibition vomiting center.The Rhizoma Pinelliae has antitussive and phlegm-dispelling functions.Rare alcohol of the Rhizoma Pinelliae or water diffuse out liquid zoopery mice with tumor hepatocarcinoma (HCA), murine sarcoma S180 and human cervical carcinoma (HeLa) cell are all had the obvious suppression effect.Simultaneously, experiment shows that Rhizoma Pinelliae polysaccharide component has polymorphonuclear leukocyte (PMN) activation and antitumor action.The cultured tumor cells in vitro experiment shows that also each processed product total alkaloids of the Rhizoma Pinelliae all has inhibitory action to the growth of chronic myelogenous leukemia cell (K562).Rhizoma Zingiberis Recens is soaked the IC 50 of total alkaloids that the Rhizoma Pinelliae, Rhizoma Zingiberis Recens boil the Rhizoma Pinelliae, the vitriol Rhizoma Pinelliae, the Rhizoma Zingiberis Recens vitriol Rhizoma Pinelliae all less than 100 μ g/ml, and the strongest with the effect of the anti-K562 growth of tumour cell of the vitriol Rhizoma Pinelliae.Pinellin 30mg/kg subcutaneous injection has the pregnant effect of tangible drought resisting to mice, and the antiearly pregnancy rate can reach 100%.The Rhizoma Pinelliae has antiarrhythmic effect.Pinellin also is a kind of phytohemagglutinin, and it and rabbit erythrocyte have single-minded hemagglutinative vigor, and concentration is low to moderate every milliliter 2 μ g and still has agglutination.Someone separates from the Rhizoma Pinelliae and obtains the macromole trypsin inhibitor.5% Rhizoma Pinelliae infusion has the effect of anti-dermatophyte.

The pharmacological action of Poria: 25% Poria alcohol preserved material is given normal rabbit lumbar injection 0.5g/Kg, diuresis occurs.Prove that with adrenalectomized rat experiment diuresis is relevant with the absorption that influences renal tubules Na+.Pachymaran has inhibitory action to murine sarcoma S180, and suppression ratio reaches 96.88%.White man worker's deep layer is cultivated in the Poria mycelium that obtains, and 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 have the contraction of enhancing, accelerate heart rate function isolated frog heart.Decoct is Poria cum Radix Pini's injection particularly, and animal is had sedation.

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 0.02g (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 Fructus Forsythiae: Fructus Forsythiae is a kind of wide spectrum and effective antimicrobial agents, in vitro tests has inhibitory action to many antibacterials, as to staphylococcus aureus, Hemolytic streptococcus, Diplococcus pneumoniae, bacillus pyocyaneus, Bacillus typhi, leptospira etc.The antimicrobial main effective ingredient of Fructus Forsythiae is Fructus Forsythiae fat glycoside and forsythin.Fructus Forsythiae can suppress Folium Digitalis Purpureae to Columba livia intravenous injection emetic action, reduces the vomiting number of times, but does not change the incubation period of vomiting, and it is similar with the effect of injection chlorpromazine after 2 hours that effect is told in its town.Fructus Forsythiae has the effect that obviously alleviates liver degeneration and necrosis to the rat of the hepatic injury that carbon tetrachloride causes, make hepatic glycogen and the rna content recovery or approaching normal of most of animals, serum glutamic pyruvic transminase is active significantly to be reduced, this shows the anti-liver injury effect, and the clinical observation Fructus Forsythiae has effect preferably to acute hepatitis.In addition, Fructus Forsythiae also has effects such as antiinflammatory, blood pressure lowering.

The pharmacological action of Semen Raphani: Semen Raphani gives birth to product and the processed product through frying, processing can make the shrinkage amplitude of isolated rabbit intestinal increase, but the tonicity of isolated rabbit intestinal is not had obvious influence; Three kinds of goods all can be to the inhibitory action of antiadrenergic drug to intestinal tube.Semen Raphani (parched) has tangible progradation to mouse small intestine; Three kinds of preparations all have inhibitory action to the mice gastric emptying.Semen Raphani water logging agent (1: 3) in vitro to Trichophyton concentricunm, permitted dermatophytess such as blue achorion, Du's big belly microspore tinea bacterium difficult to understand, rust microspore's tinea bacterium, ulotrichy microspore's tinea bacterium, star-shaped nocardia in various degree inhibitory action all arranged.Semen Raphani contains antibiotic substance, and its effective ingredient is a raphanin.Staphylococcus and escherichia coli there is remarkable inhibitory action; Also can suppress growths such as streptococcus, pyococcus, streptococcus pneumoniae, escherichia coli.Raphanin also has inhibitory action to virus, is sensitivity with DNA viruses than RNA viruses.Semen Raphani water-alcohol extract is given cat and dog intravenous injection, and very significantly hypotensive effect is arranged; Extractum is irritated harmonization of the stomach kidney type Hypertensive Rats to rabbit and is irritated stomach, and significant hypotensive effect is also arranged.Semen Raphani can obviously prolong the blood pressure lowering time.The rat Semen Raphani extract of feeding for a long time can disturb it thyroxinic synthetic.The Semen Raphani aqueous extract is given rats by intraperitoneal injection, and granulomatous inflammatory hyperplasia has obvious inhibitory action to the Fructus Crotonis oiliness, but a little less than the impervious effect.By separating the B-sitosterol that proposes in the Semen Raphani certain antitussive, phlegm-dispelling functions are arranged, for Semen Raphani treatment tracheitis provides rationale; This composition still can be treated the human serum cholesterol and be raise, prevents coronary atherosclerosis, and prompting is also having certain effect aspect the treatment coronary heart disease.

Novelty and breakthrough that the present invention has essence are to have found out the key point that lenitive pill 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 lenitive pill " 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 lenitive pill 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 lenitive pill and production method thereof, wherein: this integrated novel form raw materials of effective components and weight proportion---18 parts of Fructus Crataegis, 6 parts of Massa Medicata Fermentata, 9 parts of the Rhizoma Pinelliaes, 9 parts in Poria, 3 parts of Pericarpium Citri Reticulataes, 3 parts of Fructus Forsythiaes, 3 parts of Semen Raphanis.

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 lenitive pill 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 lenitive pill 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 lenitive pill 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 lenitive pill 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 lenitive pill 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% Fructus Crataegi, Massa Medicata Fermentata, the Rhizoma Pinelliae, 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% Pericarpium Citri Reticulatae, Fructus Forsythiae, Semen Raphani 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 lenitive pill 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 lenitive pill 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 lenitive pill 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 lenitive pill 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 lenitive pill 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 lenitive pill " 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 lenitive pill and production method thereof, its special feature is: making the raw materials of effective components composition is by weight ratio---18 parts of Fructus Crataegis, 6 parts of Massa Medicata Fermentata, 9 parts of the Rhizoma Pinelliaes, 9 parts in Poria, 3 parts of Pericarpium Citri Reticulataes, 3 parts of Fructus Forsythiaes, 3 parts of Semen Raphanis.

Further, play the synergy of standing like the legs of a tripod on the integrated new drug formulation compatibility of lenitive pill of the present invention: 1, prepare nanometer, micro-powder, the bioavailability after strengthening the lenitive pill 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 lenitive pill 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 lenitive pill 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% Fructus Crataegi, Massa Medicata Fermentata, the Rhizoma Pinelliae, Poria 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% Pericarpium Citri Reticulatae, Fructus Forsythiae, Semen Raphani 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---18 parts of Fructus Crataegis, 6 parts of Massa Medicata Fermentata, 9 parts of the Rhizoma Pinelliaes, 9 parts in Poria, 3 parts of Pericarpium Citri Reticulataes, 3 parts of Fructus Forsythiaes, 3 parts of Semen Raphanis.

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---18 parts of Fructus Crataegis, 6 parts of Massa Medicata Fermentata, 9 parts of the Rhizoma Pinelliaes, 9 parts in Poria, 3 parts of Pericarpium Citri Reticulataes, 3 parts of Fructus Forsythiaes, 3 parts of Semen Raphanis.

Its manufacture process is as follows: in 10000 grades of toilets of GMP 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---18 parts of Fructus Crataegis, 6 parts of Massa Medicata Fermentata, 9 parts of the Rhizoma Pinelliaes, 9 parts in Poria, 3 parts of Pericarpium Citri Reticulataes, 3 parts of Fructus Forsythiaes, 3 parts of Semen Raphanis.

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 lenitive pill 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 lenitive pill 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 lenitive pill and production method thereof is characterized in that: 18 parts of this novel form raw materials of effective components and weight proportion---Fructus Crataegis, 6 parts of Massa Medicata Fermentata, 9 parts of the Rhizoma Pinelliaes, 9 parts in Poria, 3 parts of Pericarpium Citri Reticulataes, 3 parts of Fructus Forsythiaes, 3 parts of Semen Raphanis.

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 lenitive pill 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 lenitive pills 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 lenitive pill 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 lenitive pill 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 lenitive pill 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% Fructus Crataegi, Massa Medicata Fermentata, the Rhizoma Pinelliae, 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% Pericarpium Citri Reticulatae, Fructus Forsythiae, Semen Raphani 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 lenitive pill 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 lenitive pill 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 lenitive pill 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 lenitive pill 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.