CN102283926A - Preparation technology and production method for novel integrated dosage form of liver fire-purging and stomach-regulating pill - Google Patents
Preparation technology and production method for novel integrated dosage form of liver fire-purging and stomach-regulating pill Download PDFInfo
- Publication number
- CN102283926A CN102283926A CN2010102011430A CN201010201143A CN102283926A CN 102283926 A CN102283926 A CN 102283926A CN 2010102011430 A CN2010102011430 A CN 2010102011430A CN 201010201143 A CN201010201143 A CN 201010201143A CN 102283926 A CN102283926 A CN 102283926A
- Authority
- CN
- China
- Prior art keywords
- medicine
- preparing
- novel form
- technology
- nano
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention relates to a preparation technology and production method for a novel integrated dosage form of a liver fire-purging and stomach-regulating pill. The novel integrated dosage form comprises the following raw materials containing effective ingredients: 6 parts by weight of coptis chinensis and 1 part of fructus evodiae. The production method comprises the steps including supersonic airflow pulverizing, alcohol water extraction, ultrasonic crushing extraction, water frying concentration, supersonic spraying and drying, high-pressure homogenizing, nano-grinding, 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
Technical field
The present invention relates to the integrated novel form technology of preparing of a kind of Zuojin Wan, the invention still further relates to integrated novel form technology of preparing of a kind of Zuojin Wan 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, otherwise modern Chinese medicine can be gone astray! 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 quickening new Chinese medicine developmental research speed, improve 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.At China's national situation, 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.
Zuojin Wan be for Zhu Danxi " danxi's experiential therapy. the fire six " name side, have another name called back make ball (" danxi's experiential therapy. fire six " volume one), cornel connects ball (" Elementary Medicine " volume seven), Zhu and connects ball (" collection of prescriptions with notes "), helps golden ball (" the Zhang Shi doctor is logical " volume 16) etc., former side is made up of Rhizoma Coptidis six liang of (frying with Sucus Zingberis) and Fructus Evodiaes one or two (using the salt blister), be the end altogether, making the watered pill or cake is ball, and the plain soup clothes down.Modern times are often got the end, and general with water is ball, obeys 3g at every turn; Or go into decoction in former ratio and take.Effect energy clearing away liver-fire, stopping nausea and vomiting by lowering the adverse flow of QI.The distending pain over the hypochondrium that is used for the treatment of the Liver Channel hyperactivity of fire, vomiting acid regurgitation, gastric upset and eructation, bitter taste in the mouth and dry throat, red tongue, wiry and frequent pulse.Zuojin Wan is through China secular a large amount of clinical uses, confirms that already it is evident in efficacy and has no side effect.For its novel form development provides good basis.
Rhizoma Coptidis nature and flavor bitter cold in the Zuojin Wan, the fire of the clear eliminating pathogen in the liver stomach of energy, six times of consumptions, are equipped with hot Fructus Evodiae warming the liver sending down the abnormal ascending QI, and can alleviate the fraud that the Rhizoma Coptidis bitter cold is upset one's stomach as monarch drug in Fructus Evodiae.The property of two medicines, a Wen Yihan, opposite fully, Fructus Evodiae plays the usefulness of using corrigent; One hardship is fallen a suffering and is opened, and catharsis liver gastric qi machine falls and lets out the contrary gas of liver stomach altogether, works coordinate wonderful.The meaning of its compatibility, there are many argumentations in doctor family, as prince connect " ancient prescription choosing annotate " meaning " running course of channel, a left side rises the right side and falls, medicinal toil, the respectful row that falls is in Sheng Dao, so day left golden.Fructus Evodiae is gone into the diffusing gas of liver, falls very prompt; Raw in the bitter dry stomach of Rhizoma Coptidis wins the heat in the stomach ... be decrease its gas with drop-down it, the method for seven damages is also "; Also as " collection of prescriptions with notes " say: " excess of the liver is then had a pain, and the son of heart person liver rushes down its son actually, so be monarch with the Rhizoma Coptidis eliminating heart-fire, makes the fire gold that is unable to, and goldenly can make woodenly, and then liver is put down.Fructus Evodiae is hot, the cloudy liver that can go into to faint, and promoting QI circulation for relieving depression, again can heat conduction descending, so think using corrigent.An one cold heat, cold person's routine treatment, hot person's contrary treatment.”
Modern pharmacological research shows that Zuojin Wan can be antibacterial.Adopt the plate punch method, add Zuojin Wan solution, cultivate 24h, Zuojin Wan is stronger to the antibacterial power of staphylococcus aureus, vibrio cholera, group B streptococcus, and is inferior slightly to the bacteriostasis of dysentery bacterium, escherichia coli, Bacillus typhi.Can ease pain, use hot plate method, give mouse stomach with Zuojin Wan 6g/ (kg.d), 5d can improve mice analgesia threshold value continuously, and relatively there were significant differences with the normal saline group; Use writhing method, give mouse stomach with Zuojin Wan 6g/ (kg.d), continuous 5d, the writhing response that 0.5% acetic acid is caused has remarkable inhibitory action, and relatively there were significant differences with the normal saline group.Can also antiinflammatory, give rat oral gavage with Zuojin Wan 1g/ (kg.d), 6d can suppress cott on pellet-induced granuloma formation continuously, and relatively there were significant differences with the normal saline group.
Novelty and breakthrough that the present invention has essence are to have found out the key point that Zuojin Wan 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 Zuojin Wan " 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 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 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 the different nano-carrier dosage form technologies of preparing of Chinese medicine and unite use.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 Zuojin Wan 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 Zuojin Wan and production method thereof, wherein: this nanometer Chinese medicine raw materials of effective components and weight proportion---
6 parts of Rhizoma Coptidis, 1 part of Fructus Evodiae.
Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, organic selenium.
Integrated novel form technology of preparing of above-mentioned a kind of Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan and production method thereof, it may further comprise the steps:
Step 1: get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, standby.
Step 2: get 30%--90% alcohol-water solution that 60% Rhizoma Coptidis micropowder doubly measures 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.
Step 3: get 60% Fructus Evodiae 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 swing 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 latest edition " 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 size distribution of preparing 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.Every contains Rhizoma Coptidis and is no less than 40mg with berberine hydrochloride.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 Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan and production method thereof, wherein: its key point 1 is different utilization nano-carrier multiple techniques different according to the nanometer particle size 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 Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan " 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 medicine nanometer particle size 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 Zuojin Wan and production method thereof, its special feature is: making the raw materials of effective components composition is by weight ratio---6 parts of Rhizoma Coptidis, 1 part of Fructus Evodiae.
Further, play the synergy of standing like the legs of a tripod on the integrated new drug formulation compatibility of Zuojin Wan of the present invention: 1, prepare nanometer, micro-powder, the bioavailability after strengthening the Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan 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% Rhizoma Coptidis micropowder doubly measures 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% Fructus Evodiae 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 swing 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.Every contains Rhizoma Coptidis and is no less than 40mg with berberine hydrochloride.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---6 parts of Rhizoma Coptidis, 1 part of Fructus Evodiae.
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.Every contains Rhizoma Coptidis and is no less than 40mg with berberine hydrochloride.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---6 parts of Rhizoma Coptidis, 1 part of Fructus Evodiae.
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.Every contains Rhizoma Coptidis and is no less than 40mg with berberine hydrochloride.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---6 parts of Rhizoma Coptidis, 1 part of Fructus Evodiae.
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 gram contains Rhizoma Coptidis and is no less than 40mg with berberine hydrochloride, 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 Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan and production method thereof is characterized in that: 6 parts of this novel form raw materials of effective components and weight proportion---Rhizoma Coptidis, 1 part of Fructus Evodiae.Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, organic selenium.
2. integrated novel form technology of preparing of a kind of Zuojin Wan 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 Zuojin Wans 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 Zuojin Wan 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 Zuojin Wan 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 Zuojin Wan and production method thereof is characterized in that may further comprise the steps:
Step 1: get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, standby.
Step 2: get 30%--90% alcohol-water solution that 60% Rhizoma Coptidis micropowder doubly measures 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.
Step 3: get 60% Fructus Evodiae 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 swing 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 size distribution of preparing 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.Every contains Rhizoma Coptidis and is no less than 40mg with berberine hydrochloride.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 Zuojin Wan according to claim 6 and production method thereof; it is characterized in that: the Chinese medicine of using in described step 1, step 2, the step 3 is pulverized 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 Zuojin Wan 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, 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 Zuojin Wan 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 nanometer particle size 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 Zuojin Wan 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102011430A CN102283926A (en) | 2010-06-17 | 2010-06-17 | Preparation technology and production method for novel integrated dosage form of liver fire-purging and stomach-regulating pill |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102011430A CN102283926A (en) | 2010-06-17 | 2010-06-17 | Preparation technology and production method for novel integrated dosage form of liver fire-purging and stomach-regulating pill |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102283926A true CN102283926A (en) | 2011-12-21 |
Family
ID=45330862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102011430A Pending CN102283926A (en) | 2010-06-17 | 2010-06-17 | Preparation technology and production method for novel integrated dosage form of liver fire-purging and stomach-regulating pill |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102283926A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105209053A (en) * | 2013-03-15 | 2015-12-30 | 爱默思公司 | Composition and method for preventing, reducing, alleviating or treating idiopathic vomiting |
| US10548935B2 (en) | 2013-03-15 | 2020-02-04 | Mars, Incorporated | Composition and method for preventing, reducing, alleviating or treating idiopathic vomiting |
| CN112618624A (en) * | 2021-01-18 | 2021-04-09 | 广州中医药大学第一附属医院 | Traditional Chinese medicine composition for treating digestive system diseases and preparation method and application thereof |
-
2010
- 2010-06-17 CN CN2010102011430A patent/CN102283926A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105209053A (en) * | 2013-03-15 | 2015-12-30 | 爱默思公司 | Composition and method for preventing, reducing, alleviating or treating idiopathic vomiting |
| US10441623B2 (en) | 2013-03-15 | 2019-10-15 | Mars, Incorporated | Dietary composition and method for preventing, reducing, alleviating or treating idiopathic vomiting |
| US10548935B2 (en) | 2013-03-15 | 2020-02-04 | Mars, Incorporated | Composition and method for preventing, reducing, alleviating or treating idiopathic vomiting |
| US11419912B2 (en) | 2013-03-15 | 2022-08-23 | Mars, Incorporated | Dietary composition for preventing, reducing, alleviating or treating idiopathic vomiting |
| CN112618624A (en) * | 2021-01-18 | 2021-04-09 | 广州中医药大学第一附属医院 | Traditional Chinese medicine composition for treating digestive system diseases and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102283895A (en) | Preparation technology and production method of integrated novel Lingguizhugan decoction dosage form | |
| CN102100894A (en) | Preparation technology of new integrative formulation of free wanderer powder and production method thereof | |
| CN102100899A (en) | Preparation technology of new integrative formulation of prepared common monkshood daughter root decoction for regulating middle | |
| CN102283927A (en) | Technology for preparing novel integrated dosage form of windflower decoction | |
| CN102100813A (en) | Preparation technology of new integrative formulation of poria five powder and production method thereof | |
| CN102100751A (en) | Preparation technology of new integrative formulation of largetrifoliolious bugbane rhizome and kudzuvine root decoction and production method thereof | |
| CN102283926A (en) | Preparation technology and production method for novel integrated dosage form of liver fire-purging and stomach-regulating pill | |
| CN102283892A (en) | Preparation technology and production method of integrated novel Sanzi Yangqin decoction dosage form | |
| CN102100895A (en) | Technology for preparing novel integrative dosage form of decoction for tonifying middle-Jiao and Qi | |
| CN102100888A (en) | Preparation technology and production method of new integrative formulation of major green-blue dragon decoction | |
| CN102283937A (en) | Technology for preparing novel integrated dosage form of stomach-clearing powder and production method thereof | |
| CN102283944A (en) | Technology for preparing novel integrated dosage form of lung heat expelling powder and production method thereof | |
| CN102846746A (en) | Preparation process of integration-type novel formulation of Aconitum carmichaeli decoction and production method thereof | |
| CN102284042A (en) | Integrated novel form preparation technology for Wuqisan and production method thereof | |
| CN102283954A (en) | Integrated novel form preparation technology for polyporus umbellatus decoction and production method thereof | |
| CN102100762A (en) | Preparation technology of new integrative formulation of baical skullcap root decoction and production method thereof | |
| CN102100892A (en) | Preparation technology and production method of integrated Xiaojianzhong decoction novel dosage form | |
| CN102895615A (en) | Preparation technology and production method for integrated new formulation of tangerine peel and bamboo shavings decoction | |
| CN102552595A (en) | Siqitang integrated novel dosage form and production method thereof | |
| CN102100897A (en) | Preparation technology and preparation method of novel integrative Erchen decoction dosage form | |
| CN102283994A (en) | Integrated novel form preparation technology for powder for activating vessels and production method thereof | |
| CN102847092A (en) | Preparation process of integration-type novel formulation of Evodia rutaecarpa decoction and production method thereof | |
| CN102526287A (en) | Preparation technology and production method of novel yellow decoction integrated dosage form | |
| CN102284024A (en) | Preparation technology of integrated novel Weijing decoction dosage form | |
| CN102100756A (en) | Preparation technology of integrated rhubarb and aconite decoction novel dosage form |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20111221 |