CN102100785A - Preparation technique for xiao chengqi decoction in a novel formed formulation and production method thereof - Google Patents

Abstract

The invention relates to a preparation technique for xiao chengqi decoction (Chinese medicine decoction for reconditioning qi) in a novel formed formulation and a production method thereof. The xiao chengqi decoction comprises the following raw materials as active ingredients in percentages by weight: 12 parts of rheum officinale, 6 parts of mangnolia officinalis and 9 parts of fruit of immature citron. The production process comprises the following steps of extraction with alcohol-water, ultrasonic pulverization and extraction, microwave extraction, concentration by water decocting, spray drying at supersonic speed, high pressure homogenization, nanometer grinding, preparation of nanoparticles and the like. The xiao chengqi decoction has the advantages of multi-synergism and multi-targeting functions of nano traditional Chinese medicine and the like. After the xiao chengqi decoction is produced in industrial scales, the production cost can be greatly reduced, the product quality can be improved and the targeting and slow controlled release of the medicament can be stronger. After the medicament is made into a pellicle, the pellicle can be adhered to human skins and used for transdermal absorption treatment.

Description

Integrated novel form technology of preparing of a kind of Xiao Chengqi Tang and production method thereof

Technical field

The present invention relates to the integrated novel form of a kind of Xiao Chengqi Tang, the invention still further relates to integrated novel form technology of preparing of a kind of Xiao Chengqi Tang and production method thereof.

Background technology

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.

The principal mode of tcm clinical practice medication is a Chinese medicine compound, it is the concrete utilization of traditional Chinese medical science principle-method-recipe-medicines, embody Chinese traditional treatment and paid attention to strengthening vital QI to eliminate pathogenic factors, the rule of whole sight such as treating both the principal and secondary aspects of a disease, systematology and determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, be multisystem, many target spots and the Therapeutic Method of bringing into play comprehensive drug action at many levels, all these non-single component can be summarized and reached.The compound recipe drug effect is not only relevant with effective substance or effective substance group, and also relevant with auxiliary element.

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.

Xiao Chengqi Tang comes from Eastern Han Dynasty's Zhang Zhongjing treatise on Febrile Diseases.Xiao Chengqi Tang is one of famous prescription of Zhang Zhongjing initiative.Form by Radix Et Rhizoma Rhei, Cortex Magnoliae Officinalis, Fructus Aurantii Immaturus.Radix Et Rhizoma Rhei purging heat to relax the bowels in the side, Cortex Magnoliae Officinalis circulation of qi promoting loose full, the Fructus Aurantii Immaturus dispelling the stagnated QI painful abdominal mass that disappears, and all medicines share, and can gently descend accumulation of heat, except that the painful abdominal mass that completely disappears.Cure mainly typhoid fever excess syndrome of YANG MING FU-organ card.The delirium hectic fever, constipation, breast abdomen feeling of fullness, yellow fur, slippery and rapid pulse, dysentery from the beginning of, pestilence pain in the abdomen, or distension and fullness in the abdomen, tenesmus person.Modern times are used for the treatment of intestinal obstruction, operation back gastrointestinal dysfunction, paraplegia constipation, intestinal tract cleaning, chronic gastritis, hepatitis, biliary tract, chronic pulmonary heart disease, child disease etc.

Each tame argumentation: " interior platform side view ": card belongs to positive bright person, is all and can descends also, as if severe fullness sensation in the abdomen, severe excess syndrome person, belongs to DACHENGQI TANG.Modern this big heat, hard stool not as for severe excess syndrome, only belongs to Xiao Chengqi Tang also.With the Radix Et Rhizoma Rhei is monarch, and swings except that pathogenic heat; With the Fructus Aurantii Immaturus is minister, and broken solid; With the Cortex Magnoliae Officinalis is that assistant makes, and expel stagnation is also dry in transferring." hospital examines ": heresy then expires at the part of the body cavity above the diaphragm housing the heart and lungs, and heresy is then done to expand middle Jiao, makes hectic fever in the stomach actually, and sun is taken advantage of in the heart then mad, and heat is done appetite and then breathed heavily, and trifoliate orange, Piao remove the feeling of fullness of the part of the body cavity above the diaphragm housing the heart and lungs, and Radix Et Rhizoma Rhei swings the excess-heat in the stomach.Though this its interior syndrome becomes, disease is not critical, and painful abdominal mass, full, dry, reality, heavily fortified point are still complete all, with the side of being master, then gas is also suitable, holds gas for a short time so say." the attached wing of typhoid fever ": all diseases of husband are affection of wind all, not the going of dirty thing because the having some setbacks of gas, so attack long-pending agent, must be with the medicine of circulation of qi promoting with master, highly then do harm to.Holding is system, and this holds the reason of gas.Disease is gone and vigour is not hindered again, and this justice of holding gas also; Radix Et Rhizoma Rhei times Cortex Magnoliae Officinalis is that the gas medicine is a minister, and name is held gas for a short time.Flavor is few, and property is slow, make for a short time, and its clothes are desired slightly regulating stomach-QI also, so say little.Three things are regardless of order with frying in shallow oil, and clothes only four close, and this asks genuine logical, thus without awns disappear high, and be distal to the sharp of Radix Et Rhizoma Rhei, thus be called little with agent.Press in " reformulating popular Treatise on Febrile Diseases " what Xiushan Mountain: the small intestine fire internal organs, and non-hardship is obstructed, so monarch is with the bitter cold of the army of giving birth to, to wash small intestinal; Minister falls with the hardship of Fructus Aurantii Immaturus, through pylorus; But bitter non-suffering is obstructed, and Gu Zuo helps the success of general's World War I also with the toil of Cortex Magnoliae Officinalis.This is positive bright excess-heat, the good recipe of penting up small intestinal." ancient prescription choosing annotate ": the person that holds gas, below hold also, follow the example of ground, lid ground be the road of money lifes with restricted, so as if excess syndrome of YANG MING FU-organ, stercoroma is not all right in order to gush the machine of letting out with bitter for stomach, the tunnel mistake is to go in fact with method for making.Radix Et Rhizoma Rhei Sichuan Cortex Magnoliae Officinalis (processed), bitter flavor prevailing over pungent flavor also, Cortex Magnoliae Officinalis system Fructus Aurantii Immaturus, pungent flavor prevailing over sour flavor also, acid is real to win gastric qi, it is bitter that hot stercoroma goes to open the constipated of large intestine to change the waste matter of small intestinal, genuine logical, cloudy air bearing holds gas so say.Solely control excess of the stomach, so say little.

Modern pharmacological research shows: it mainly contains antibiotic, protects the liver, and reduces effects such as vascular permeability.

1. antibiotic: the in-vitro antibacterial test confirms that Xiao Chengqi Tang stock solution and concentrated solution all have antibacterial action to escherichia coli and staphylococcus, and the Xiao Chengqi Tang concentrated solution is particularly evident to the staphylococcus antibacterial action.

2. protect the liver: Xiao Chengqi Tang has the restoration and protection effect to the carbon tetrachloride hepatic injury rat liver.Xiao Chengqi Tang group and hepatic injury group compare, and the lobules of liver damage zone dwindles, and the hepatocyte fat drop reduces, and RNA increases, and glycogen increases, enzymes such as SDH (succinate dehydrogenase, mitochondrion marker enzyme) increased activity.Electron microscopic observation, Xiao Chengqi Tang group rough endoplasmic reticulum dense arrangement, it is normal that structure of mitochondria is recovered, and quantity increases.Its mechanism of action may be by stoping the mitochondrial damage of endoplasmic reticulum, promote protein synthesis and improve the cell aerobic metabolism, thereby promote the reparation of cell, recovering liver function.

3. reduction vascular permeability: mouse tail vein injects the 125I-albumin, and the radioactive activity of measuring in the mouse peritoneal liquid shows that Xiao Chengqi Tang can reduce vascular permeability, suppresses foreign body and oozes out from blood circulation, reduces the quantity that foreign body enters the abdominal cavity.

Novelty and breakthrough that the present invention has essence are to have found out the key point that Xiao Chengqi Tang nanometer Chinese medicine compound 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 Xiao Chengqi Tang " field with theory of integrated Chinese and western medicine, product has the targeting advantage such as wide that distributes, and does not have identical or similar bibliographical information both at home and abroad.Research and development have reached world lead level.Show substantive progressive and novelty of the present invention by international one-level novelty assessment report and patent 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.

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 Xiao Chengqi Tang and production method thereof are provided.

Purpose of the present invention is achieved through the following technical solutions:

Integrated novel form technology of preparing of a kind of Xiao Chengqi Tang and production method thereof, wherein: this integrated novel form raw materials of effective components and weight proportion---

12 parts of Radix Et Rhizoma Rhei, 6 parts of Cortex Magnoliae Officinalis, 9 parts of Fructus Aurantii Immaturuss.

Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, organic selenium.Described Chinese medicine is not only the above-mentioned Chinese medicine of respectively distinguishing the flavor of of described amount ranges, and other do not influence its disease of controlling to be also included within its basic upward interpolation, and just make the medicine of its better efficacy.

Integrated novel form technology of preparing of above-mentioned a kind of Xiao Chengqi Tang and production method thereof, wherein: medicine is become medicine support material medicine with preparing carriers, crude drug can be one or more combinations in nanoparticle, nanoparticle, micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, the microcapsule etc., and can one or more be mixed according to different needs.Described crude drug is not only the above-mentioned raw materials medicine in the described scope, and other do not influence its disease of controlling to be also included within its basic upward preparation interpolation, and just make the crude drug of its better efficacy.

Further, integrated novel form technology of preparing of above-mentioned a kind of Xiao Chengqi Tang and production method thereof, wherein: the drug carrier material that this novel form is selected for use, activating agent, help Emulsion, excipient substances such as dispersant are gelatin, albumin and 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 and 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 is (as glyceryl monostearate, contain list, two, the synthetic glyceride of triglyceride), steroidal class (cholesterol etc.), Polyethylene Glycol, wax class (microcrystalline wax, whale ester type waxes), erythrocyte, Montmorillonitum, in the bentonite 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 Xiao Chengqi Tang and production method thereof, wherein: the integrated novel form end product that finally can form is: tablet, powder, suppository, stick, granule, soft capsule, hard capsule, effervescent, drop pill, aerosol, injection, unguentum, oral solution, slow releasing tablet, controlled release tablet.

Again further, integrated novel form technology of preparing of above-mentioned a kind of Xiao Chengqi Tang and production method thereof, wherein: indexs such as said integrated novel form is moving according to pharmacology, drug effect, the medicine of traditional Chinese medical science global theory, compatibility theory and medicine, toxicity, adopt 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 pharmaceutical carriers.And can mix its one or more as required.

Integrated novel form technology of preparing of a kind of Xiao Chengqi Tang and production method thereof, it may further comprise the steps:

Step 1: get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, standby.

Step 2: get 30%-90% alcohol-water solution that 60% Radix Et Rhizoma Rhei 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% Cortex Magnoliae Officinalis micropowder, adopt the high-frequency ultrasonic of independent research to disperse the pulverizing extraction equipment 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: get 60% Fructus Aurantii Immaturus micropowder, adopt the swing nanon ball-mill of independent research to grind 4-16 hour, particle size distribution be the nano powder of 50-1000 nanometer, standby.

Step 5: 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.

Step 6: with step 2, step 3, step 4 gained Chinese medicine extract, nano powder difference according to different needs and the property of medicine, pharmacology, " the corresponding code requirement of standard preparation adopts technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to be prepared respectively in the Chinese pharmacopoeia, gets medicine materials such as different pharmaceutical monomer, effective site, active substance by latest edition.

Step 7: the said medicine raw material is adopted different excipient substances, and " preparation part of standards standard is with " the even method of high pressure breast is adopted in the requirement among the Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " etc. respectively in the Chinese pharmacopoeia by latest edition, inclusion technique, solid state technology, polishing, solvent-fusion method, the Double helix 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: by " preparation part of standards code requirement in the Chinese pharmacopoeia is got in the crude drug such as step 5 gained Chinese medical concrete or water drug-decocting concentrating liquid and step 7 gained 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, microcapsule one or more and mixed.

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 latest edition " 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 Xiao Chengqi Tang and production method thereof, wherein: the Chinese medicine of using in described step 1, step 2, the step 3 is pulverized and extracting method, described above-mentioned technology of preparing and the method for not only referring to, as required, be also included within add on its basis or use other better effects if, more economical, upgrade, more advanced breaking method, extracting method and technology.

Further, integrated novel form technology of preparing of above-mentioned a kind of Xiao Chengqi Tang and production method thereof, wherein: the medicine monomer in the described step 6, active substance, effective site technology of preparing, described above-mentioned technology of preparing and the method for not only referring to, as required, be also included within add on its basis or use other better effects if, more economical, upgrade, more advanced preparation method and technology.

Further, integrated novel form technology of preparing of above-mentioned a kind of Xiao Chengqi Tang and production method thereof, wherein: the dissimilar crude drug such as nanoparticle that adopt the different pharmaceutical adjuvant to be prepared in the described step 7, described above-mentioned technology of preparing and the method for not only referring to, as required, be also included within add on its basis or use other better effects if, more economical, upgrade, more advanced preparation method and technology.

Again further, integrated novel form technology of preparing of above-mentioned a kind of Xiao Chengqi Tang and production method thereof, wherein: its key point is the different and property of medicine and use the different of carrier according to the nanometer particle size of crude drug, can produce the different targeting controlled capability that eases up.

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 Xiao Chengqi Tang nanometer Chinese medicine compound 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 Xiao Chengqi Tang " field with theory of integrated Chinese and western medicine, product has the targeting advantage such as wide that distributes, and does not have identical or similar bibliographical information both at home and abroad.Research and development have reached world lead level.Show substantive progressive and novelty of the present invention by international one-level novelty assessment report and patent 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.

Novelty and breakthrough that the present invention has essence are to have found out the key point that Xiao Chengqi Tang nanometer Chinese medicine compound Chinese and western medicine theory combines, and the compound compatibility of nanometer Chinese medicine can change the pharmacokinetic parameter of effective ingredient or parts formulation.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, Tai Ji, Buddhism, Taoism, Huang di's Canon of Medicine, is simple philosophic thinking, 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, road doctor's homology.This theoretical basis of the present invention just.Among the present invention: medicine monomer, effective site, nanoparticulate carriers etc. be strange, be tiny, be cloudy.Traditional Chinese medical science organic conception thought, 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 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.

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 in 10 nanometers---between 10 microns.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.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, in be western usefulness, westernly a practical effective novel form compatibility program has been proposed for middle usefulness.Be to have substantial technological break-through and theory of integrated Chinese and western medicine breakthrough.Will promote scientific and technological content and traditional Chinese medical science reform plays important exemplary role for the traditional traditional Chinese medical science.Also will promote the development of China's Chinese medicine industry.

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 Xiao Chengqi Tang and production method thereof, its special feature is: making the raw materials of effective components composition is by weight ratio---

12 parts of Radix Et Rhizoma Rhei, 6 parts of Cortex Magnoliae Officinalis, 9 parts of Fructus Aurantii Immaturuss.

Further, play the synergy of standing like the legs of a tripod on the integrated new drug formulation compatibility of Xiao Chengqi Tang of the present invention: 1, prepare nanometer, micro-powder, strengthen Xiao Chengqi Tang therapeutic effect and not clear active substance group's therapeutical effect 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 Xiao Chengqi Tang with this; 3, prepare Chinese medical concrete, water drug-decocting concentrating liquid with the prepared slices of Chinese crude drugs, the temporary transient unpredictable drug effect of bringing with this reaction such as complexation, hydrolysis, oxidation, reduction of strengthening Xiao Chengqi Tang Chinese medicine compound uniqueness also keeps and has strengthened traditional Chinese medical science organic conception, monarch notion.More than three aspects associatings compatibility use, different according to Nano medication particle diameter and character, can reach effects such as many targeting, many collaborative, slow controlled releases, and play useful effect to strengthening the medicine pharmacologically active, effective ingredient pharmacological action effect is significantly higher than conventional formulation.

Production method of the present invention may further comprise the steps: at first, gets each prepared slices of Chinese crude drugs pretreatment, inserts pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, and standby.Get 30%-90% alcohol-water solution that 60% Radix Et Rhizoma Rhei 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% Cortex Magnoliae Officinalis 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.Get 60% Fructus Aurantii Immaturus micropowder, adopt the swing nanon ball-mill of independent research to grind 4-16 hour, obtain the nano powder that particle size distribution is the 50-1000 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 above-mentioned gained Chinese medicine extract, nano powder difference according to different needs and the property of medicine, pharmacology, " the corresponding code requirement of standard preparation adopts technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to be prepared respectively in the Chinese pharmacopoeia, gets medicine materials such as different pharmaceutical monomer, effective site, active substance by latest edition.The said medicine raw material is adopted different excipient substances, and " preparation part of standards standard is with " the even method of high pressure breast is adopted in the requirement among the Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " etc. respectively in the Chinese pharmacopoeia by latest edition, inclusion technique, solid state technology, polishing, solvent-fusion method, the Double helix 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.By " preparation part of standards code requirement in the Chinese pharmacopoeia is got in the crude drug such as above-mentioned gained Chinese medical concrete or water drug-decocting concentrating liquid and above-mentioned gained 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, microcapsule one or more and mixed.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 latest edition " Chinese pharmacopoeia related preparations standard criterion is made the above-mentioned end product of other type.The end product of making is carried out several respectively, bottles, adorns box, seals, pastes labeling, plays exterior and interior packings such as sign indicating number, vanning.Packaged product is transported to the appointed place by production batch and unifies instantaneously sterilising, and opens the sterilization report.

" embodiment one "

Press the following crude drug of preceding method preparation:

Extractum, nanoparticle, microcapsule, nanoparticle.

It makes the raw materials of effective components composition---

12 parts of Radix Et Rhizoma Rhei, 6 parts of Cortex Magnoliae Officinalis, 9 parts of Fructus Aurantii Immaturuss.

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 latest edition " Chinese pharmacopoeia preparation part hard capsule standard, 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, nanometer suspension liquid.

It makes the raw materials of effective components composition---

12 parts of Radix Et Rhizoma Rhei, 6 parts of Cortex Magnoliae Officinalis, 9 parts of Fructus Aurantii Immaturuss.

Its manufacture process is as follows:

In GMP10000 level toilet with water drug-decocting concentrating liquid, liposome, nano-emulsion, microemulsion, nanometer suspension liquid in 5: 1: 1: after ratio was mixed in 2: 1, adopt latest edition " Chinese pharmacopoeia preparation part soft capsule standard, 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, solid lipid nanoparticle, nano-emulsion.

It makes the raw materials of effective components composition---

12 parts of Radix Et Rhizoma Rhei, 6 parts of Cortex Magnoliae Officinalis, 9 parts of Fructus Aurantii Immaturuss.

Its manufacture process is as follows:

In GMP10000 level toilet with extractum, solid lipid nanoparticle, nano-emulsion in 4: 3: 3: after 2 ratios were mixed, " Chinese pharmacopoeia preparation part membrane standard, filmogen adopted polyvinyl alcohol, makes membrane to adopt latest edition.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 content of dispersion is the 1.2-5 gram, 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: 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 Xiao Chengqi Tang " field with theory of integrated Chinese and western medicine, product has the targeting advantage such as wide that distributes, and does not have identical or similar bibliographical information both at home and abroad.Novelty and breakthrough that the present invention has essence are to have found out the key point that Xiao Chengqi Tang nanometer Chinese medicine compound Chinese and western medicine theory combines, and the various Chinese medicine nanometer particle size major parts of preparing are the granule of 50～1000 nanometers.Adopting different nano-medicament carriers to be prepared into nanoparticle, nanosphere, nanocapsule, solid ester matter nanoparticle, magnetic nano particle, immune nano grain, nano-emulsion, vesicle, pharmacosomes, microcapsule, nanoparticle, millimicro ball, millimicro assists etc.Its particle size distribution is in 10 nanometers---between 10 microns.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, in be western usefulness, westernly a practical effective novel form compatibility program has been proposed for middle usefulness.Be to have substantial technological break-through and theory of integrated Chinese and western medicine breakthrough.Will promote scientific and technological content and traditional Chinese medical science reform plays important exemplary role for the traditional traditional Chinese medical science.

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.

Claims (10)

1. integrated novel form technology of preparing of Xiao Chengqi Tang and production method thereof is characterized in that: this integrated novel form raw materials of effective components and weight proportion---

12 parts of Radix Et Rhizoma Rhei, 6 parts of Cortex Magnoliae Officinalis, 9 parts of Fructus Aurantii Immaturuss.

Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, organic selenium.The described protection domain of this claim is not only the above-mentioned Chinese medicine of respectively distinguishing the flavor of of described amount ranges, and other do not influence its disease of controlling to be also included within its basic upward interpolation, and just make the medicine of its better efficacy.

2. integrated novel form technology of preparing of a kind of Xiao Chengqi Tang according to claim 1 and production method thereof, it is characterized in that: medicine is become medicine support material medicine with preparing carriers, crude drug can be one or more combinations in nanoparticle, nanoparticle, micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, the microcapsule etc., and can one or more be mixed according to different needs.The described protection domain of this claim is not only the above-mentioned raw materials medicine in the described scope, and other do not influence its disease of controlling to be also included within its basic upward preparation interpolation, and just make the crude drug of its better efficacy.

3. according to claim 1, integrated novel form technology of preparing of 2 described a kind of Xiao Chengqi Tang and production method thereof, it is characterized in that: the drug carrier material that this novel form is selected for use, activating agent, help Emulsion, excipient substances such as dispersant are gelatin, albumin and 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 and 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 is (as glyceryl monostearate, contain list, two, the synthetic glyceride of triglyceride), steroidal class (cholesterol etc.), Polyethylene Glycol, wax class (microcrystalline wax, whale ester type waxes), erythrocyte, Montmorillonitum, in the bentonite 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 Xiao Chengqi Tang and production methods thereof, it is characterized in that: the integrated novel form end product that finally can form is: tablet, powder, suppository, stick, granule, soft capsule, hard capsule, effervescent, drop pill, aerosol, injection, unguentum, oral solution, slow releasing tablet, controlled release tablet.

5. according to claim 1 or 2 or 3 or 4 any integrated novel form technology of preparing of described a kind of Xiao Chengqi Tang and production methods thereof, it is characterized in that: indexs such as said integrated novel form is moving according to pharmacology, drug effect, the medicine of traditional Chinese medical science global theory, compatibility theory and medicine, toxicity, adopt 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, carrier.And can mix its one or more as required.

6. integrated novel form technology of preparing of Xiao Chengqi Tang and production method thereof is characterized in that may further comprise the steps:

Step 1: get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine micropowder, standby.

Step 2: get 30%--90% alcohol-water solution that 60% Radix Et Rhizoma Rhei 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% Cortex Magnoliae Officinalis micropowder, adopt the high-frequency ultrasonic of independent research to disperse the pulverizing extraction equipment 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: get 60% Fructus Aurantii Immaturus micropowder, adopt the swing nanon ball-mill of independent research to grind 4-16 hour, particle size distribution be the nano powder of 50-1000 nanometer, standby.

Step 5: 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.

Step 6: with step 2, step 3, step 4 gained Chinese medicine extract, nano powder difference according to different needs and the property of medicine, pharmacology, " the corresponding code requirement of standard preparation adopts technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to be prepared respectively in the Chinese pharmacopoeia, gets medicine materials such as different pharmaceutical monomer, effective site, active substance by latest edition.

Step 7: the said medicine raw material is adopted different excipient substances, and " preparation part of standards standard is with " the even method of high pressure breast is adopted in the requirement among the Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " etc. respectively in the Chinese pharmacopoeia by latest edition, inclusion technique, solid state technology, polishing, solvent-fusion method, the Double helix 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: by " preparation part of standards code requirement in the Chinese pharmacopoeia is got in the crude drug such as step 5 gained Chinese medical concrete or water drug-decocting concentrating liquid and step 7 gained 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, microcapsule one or more and mixed.

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 latest edition " 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 Xiao Chengqi Tang 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 add on its basis or use other better effects if, more economical, upgrade, more advanced breaking method, extracting method and technology.

8. integrated novel form technology of preparing of a kind of Xiao Chengqi Tang according to claim 7 and production method thereof; it is characterized in that: the medicine monomer in the described step 6, active substance, effective site technology of preparing; 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, more advanced preparation method and technology.

9. integrated novel form technology of preparing of a kind of Xiao Chengqi Tang according to claim 8 and production method thereof; it is characterized in that: the dissimilar crude drug such as nanoparticle that adopt the different pharmaceutical adjuvant to be prepared in the described step 7; 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, more advanced preparation method and technology.

10. integrated novel form technology of preparing of a kind of Xiao Chengqi Tang according to claim 9 and production method thereof, it is characterized in that: its key point is the different and property of medicine and use the different of carrier according to the nanometer particle size of crude drug, can produce the different targeting controlled capability that eases up.