CN102100768A - Preparation technique for ephedra decoction in novel formed formulation and production method thereof - Google Patents

Abstract

The invention relates to a preparation technique for ephedra decoction in a novel formed formulation and a production method thereof. The ephedra decoction comprises the following raw materials as active ingredients in percentages by weight: 9 parts of ephedra, 6 parts of cassia twig, 6 parts of almond and 3 parts of liquorice. The production process comprises the following steps of extraction with alcohol-water, ultrasonic pulverization and extraction, microwave extraction, concentration by water decocting, spray drying, high pressure homogenization, nanometer grinding, preparation of nanoparticles and the like. The ephedra decoction has the advantages of multi-synergism and multi-targeting functions of nano traditional Chinese medicine and the like. After the ephedra 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 Ephedrae Decoction and production method thereof

Technical field

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

Background technology

New drug, novel form exploitation level can embody the economy and the technical strength of the medical industry of a country.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.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.China's drug control relevant laws and regulations regulation changes dosage form and manages as new drug research.

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.

Ephedrae Decoction comes from the treatise on Febrile Diseases of Han dynasty Zhang Zhongjing.Ephedrae Decoction is the representative prescription of relieving the exterior syndrome with drugs of pungent in flavor and warm in nature.Diaphoresis with drugs pungent in flavor and warm in nature is arranged, disperse the effect of separating from antiperspirant in the heresy of the wind and cold of showing.Cure mainly typhoid fever Solar watch excess syndrome.Herba Ephedrae bitter in the mouth suffering is warm in nature, is the special medicine of lung meridian, can send out human body more, and the effect of relieving the exterior syndrome by diaphoresis, depressed lung-energy dispersing is arranged, thus the monarch drug in the side of being, and the side's of being used as name.Because battalion is puckery to be defended strongly fragrantly, single use the Herba Ephedrae diaphoresis, but Xie Wei gas is strongly fragrant, so use dispelling cold by warming the meridian again, it is minister that saturating battalion reaches the Ramulus Cinnamomi of defending, and strengthens relieving the exterior syndrome by diaphoresis and dispersing wind and cold, removes body and aches.Breathing heavily of assertive evidence is that due to the superinverse, Herba Ephedrae, Ramulus Cinnamomi are all up and diffusing again by lung qi is strongly fragrant, is adjuvant drug so join the Semen Armeniacae Amarum that falls lung qi, dispersing wind and cold again, and one a surname one falls with Herba Ephedrae, strengthens the merit that resolving depression is relievingd asthma.Radix Glycyrrhizae Preparata can be in harmonious proportion a surname and fall fiber crops, Fructus Pruni, can relax the high strong property that fiber crops, osmanthus are harmonious again, makes the unlikely too quickly and damage healthy energy of sweating, is messenger drug and the justice of adjuvant drug of holding concurrently.Herba Ephedrae gets Ramulus Cinnamomi, defends the strongly fragrant of branch for one, the heresy of saturating battalion branchs, so Ke Qin comments Ephedrae Decoction to say: " this pursues high dose of evil diaphoresis also for game clock.”

Ephedrae Decoction mainly contains diaphoresis, and is analgesic, and anti-hypothermia is relievingd asthma, and antiviral is adjusted effects such as immunologic function.Modern clinical treatment influenza, infantile hyperpyrexia, bronchial asthma, the rheumatoid arthritis etc. of being mainly used in.Since the Han dynasty, the clinical application effect of Ephedrae Decoction is fully verified.

The Ephedrae Decoction pharmacological action:

1. diaphoresis: Ephedrae Decoction is typical diaphoresis side, adopts the perspiration quantitative measurement device, observes the perspiration of Ephedrae Decoction to rat. after finding that rats gavaged is equivalent to the Ephedrae Decoction of 30 times of people's consumptions, the sweat evaporation amount of sufficient sole of the foot portion is apparently higher than matched group in 2 hours.The perspiration of Ephedrae Decoction and square epheday intermedia, Ramulus Cinnamomi medicine are to relevant.Ephedrae Decoction is significant amount-effect dependency to the perspiration of rat, and recording its minimum effective dose is 0.04/kg (gastric infusion); The effect that is equivalent to clinical equivalent dosage half-life of disappearing is 2.54 hours; It is 16.39 hours that effect is held time; The effect peak time is 1.96 hours.In addition, Ephedrae Decoction can also promote the secretion of mice lachrymal gland and salivary gland.

2. analgesic: rabbit vein injection Ephedrae Decoction crude preparation by using has tangible antagonism to heating due to the triple vaccine.But also have report to think that the oral Ephedrae Decoction decoct of rabbit to the endotoxin pyrogenic animal, not only can not be lowered the temperature, the anti-heating animal heat that makes further rises.The heat effect of separating with heating rat due to fresh yeast is an index. the kinetic parameter of research Ephedrae Decoction refrigeration function, and its minimum onset amount is 0.189/kg, and be 6.4 hours action period, and biofacies is 1.11 hours when the elimination half-life of dose in the body.About diversity of each family report of Ephedrae Decoction refrigeration function, may be with route of administration, laboratory animal, pyrogen different relevant.

3. anti-hypothermia: utilize streptococcus pneumoniae to duplicate rat " class exterior cold " model, animal subcutaneous injection streptococcus pneumoniae viable bacteria, early stage at counteracting toxic substances, animal shiver with cold occurs, alarms hair, tired aversion to cold symptom such as crouch, fall with the anus relaxing the bowels with purgatives of warm nature simultaneously, the Ephedrae Decoction gastric infusion has tangible antagonism to this, show as animal aversion to cold sx, anus relaxing the bowels with purgatives of warm nature range of decrease degree reduces.In addition, Ephedrae Decoction descends to body temperature due to the rat intravenous injection antondin, and obvious antagonism is also arranged.

4. relieving asthma: Ephedrae Decoction can be alleviated bronchial muscular spasm.Its principal agent of relievining asthma is Herba Ephedrae (ephedrine), the ephedrine stable in properties, its mechanism of relievining asthma mainly is to promote adrenal gland's energy nerve and adrenal medullary chromaffin cell to discharge to remove Shen epinephrine and epinephrine, and the receptor, on the direct excited bronchial smooth muscle cell membrane, thereby activated adenyl cyclase, make ATP become cAMP, cAMP has inhibitory action to smooth muscle contraction.In addition, the water extract of Herba Ephedrae can stop the release of sensitive media, suppresses production of antibodies, can also direct excited alpha-2-adrenoceptor, make the vasoconstriction that do not disappear, and alleviate the swelling of bronchial mucosa, effectively to the outbreak of asthma and prevention.

5. antitussive: show with zooperies such as ammonia stimulus method or mechanical stimulus methods. the water solubility extract of Ephedrae Decoction and Herba Ephedrae all has tangible antitussive effect.The composition flavour of a drug of research Ephedrae Decoction find list Herba Ephedrae, Radix Glycyrrhizae, Semen Armeniacae Amarum, or Herba Ephedrae are joined Radix Glycyrrhizae, Radix Glycyrrhizae is joined Semen Armeniacae Amarum, and cough has obvious antitussive effect to the sulfur dioxide induced mice.

6. antiviral: as index, observe Ephedrae Decoction to the effect of RSV inhibition of proliferation with respiratory syncytial virus (RSV) incubation pnagus medius plaque number.Found that in the phage plaque forming process of RSV, the Ephedrae Decoction of 500 μ g/ml concentration can make the phage plaque number of RSV reduce 50%, thereby the prompting Ephedrae Decoction has the effect of the respiratory syncytial virus of anti-infantile common cold virus.

7. adjustment immunologic function: after the animals received cold stress, immunologic hypofunction occurs, be embodied in: total white blood cells and lymphocyte number descend; Atrophy of thymus gland; The mononuclear cell phagocytic function reduces; T cell transformation rate, phagocytic activity of leukocytes and hematid immunity function all descend to some extent.Ephedrae Decoction reduces immunologic function due to the cold stress, and tangible antagonism is arranged.In addition, Ephedrae Decoction can also obviously improve intact animal's antiendotoxin antibody horizontal.

8. synergistic antitumor effect: Ephedrae Decoction and antineoplastic agent cisplatin share, and can strengthen the anticancer effect of cisplatin to sarcoma S-180, Meth-A.Ephedrae Decoction also has certain cisplatin toxic action that alleviates, and rat kidney infringement due to the antagonism cisplatin to accepting the mice of fatal dose along aluminum, also has the certain protection effect.

Other: Ephedrae Decoction has certain inhibitory action to rat Ovum Gallus domesticus album foot sole of the foot portion inflammation.In addition, Ephedrae Decoction has obvious facilitation to mouse red blood cell glycolysis ability, and showing as the lactic acid production that the erythrocyte zymolysis produces in the unit interval obviously increases than matched group.

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 and abroad in the document, these project complex art characteristics have certain novelty and novelty.

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 therapeutical 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.At present, there is not identical or similar bibliographical information both at home and abroad.Proof the present invention research and development have reached world lead level.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 Ephedrae Decoction 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 Ephedrae Decoction and production method thereof, wherein: this integrated novel form raw materials of effective components and weight proportion---

9 parts in Herba Ephedrae, 6 parts of Ramulus Cinnamomi, 6 parts in Semen Armeniacae Amarum, 3 parts in Radix Glycyrrhizae

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 Ephedrae Decoction 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 Ephedrae Decoction 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 Ephedrae Decoction 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 Ephedrae Decoction 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, 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 Ephedrae Decoction 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% Herba Ephedrae, Ramulus Cinnamomi micropowder doubly measure with 6-12 and mix and soaked 1-2 days, reflux, extract, 3 times is extracted water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol, extract with standby.

Step 3: get 60% Semen Armeniacae Amarum 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% Radix Glycyrrhizae 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: above-mentioned gained medicine 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 Ephedrae Decoction 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 Ephedrae Decoction 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 Ephedrae Decoction 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 Ephedrae Decoction 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:

The present invention will in time fill up both at home and abroad in utilization " nano-carrier multiple techniques " with the blank in theory of integrated Chinese and western medicine research and development " the integrated novel form of Ephedrae Decoction " field, and product has the targeting advantage such as wide that distributes, and research and development have reached world lead level.No both at home and abroad identical or similar industrialization report." 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: 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.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 and abroad in the document, these project complex art characteristics have certain novelty and novelty.

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

9 parts in Herba Ephedrae, 6 parts of Ramulus Cinnamomi, 6 parts in Semen Armeniacae Amarum, 3 parts in Radix Glycyrrhizae

Further, play the synergy of standing like the legs of a tripod on the new drug formulation compatibility of the present invention: 1, prepare the Nano Chinese medicine powder body, strengthen its 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 Chinese medicine 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 the 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% Herba Ephedrae, Ramulus Cinnamomi micropowder doubly measure with 6-12 and mix and soaked 1-2 days, reflux, extract, 3 times is extracted water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol, extract with standby.Get 60% Semen Armeniacae Amarum 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% Radix Glycyrrhizae 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.Above-mentioned gained medicine 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 above-mentioned gained Chinese medical concrete or water drug-decocting concentrating liquid and each crude drug of above-mentioned gained 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---

9 parts in Herba Ephedrae, 6 parts of Ramulus Cinnamomi, 6 parts in Semen Armeniacae Amarum, 3 parts in Radix Glycyrrhizae

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---

9 parts in Herba Ephedrae, 6 parts of Ramulus Cinnamomi, 6 parts in Semen Armeniacae Amarum, 3 parts in Radix Glycyrrhizae

Its manufacture process is as follows:

In GMP10000 level toilet with water drug-decocting concentrating liquid, nanometer 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---

9 parts in Herba Ephedrae, 6 parts of Ramulus Cinnamomi, 6 parts in Semen Armeniacae Amarum, 3 parts in Radix Glycyrrhizae

Its manufacture process is as follows:

After in the GMP10000 level toilet extractum, solid lipid nanoparticle, nano-emulsion being mixed in 4: 3: 3 ratios, " Chinese pharmacopoeia preparation part membrane standard, filmogen adopts 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, to have the novelty and the breakthrough of essence be to have found out the key point that nanometer Chinese medicine compound Chinese and western medicine theory combines in the present invention.Simultaneously, utilization nano-carrier multiple techniques and theory of integrated Chinese and western medicine research and development " the integrated novel form of Ephedrae Decoction ", product has characteristics such as targeting distributes extensively, slow controlled release properties is strong.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.The various Chinese medicine nanometer particle size major parts that the present invention prepares 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.

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 Ephedrae Decoction " 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 industrialization report both at home and abroad.Research and development have reached world lead level.Show of the present invention substantive progressive by international one-level novelty assessment report and patent data library searching.Look into new result and do not see open report in the document at home and abroad, prove that complex art characteristics of the present invention have certain novelty and novelty.

Claims (10)

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

9 parts in Herba Ephedrae, 6 parts of Ramulus Cinnamomi, 6 parts in Semen Armeniacae Amarum, 3 parts in Radix Glycyrrhizae.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 Ephedrae Decoction 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 Ephedrae Decoctions 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 Ephedrae Decoction and production methods thereof, it is characterized in that: finally the end product that can form is: integrated novel forms such as 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 Ephedrae Decoction 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, 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.

6. integrated novel form technology of preparing of Ephedrae Decoction 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% Herba Ephedrae, Ramulus Cinnamomi micropowder doubly measure with 6-12 and mix and soaked 1-2 days, reflux, extract, 3 times, extract water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol gets extract with standby.

Step 3: get 60% Semen Armeniacae Amarum 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% Radix Glycyrrhizae 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: above-mentioned gained medicine 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 Ephedrae Decoction 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 Ephedrae Decoction 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 Ephedrae Decoction 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 Ephedrae Decoction 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.