CN102526649A - Actinolite pill integrative new formulation preparation technology and production method thereof - Google Patents

Abstract

The invention relates to actinolite pill integrative new formulation preparation technology and a production method thereof; the effective components comprise the following raw materials by weight: 2 parts of actinolite, 3 parts of fructus evodiae, 1 parts of prepared rehmannia roots, 3 parts of achyranthes roots, 3 parts of dried ginger, and 3 parts of bighead atractylodes rhizome. The production process comprises: ultrasonic jet milling, alcohol water extraction, ultrasonic crushing extraction, water decoction concentration, ultrasonic spray drying, nanometer grinding, high pressure homogenization, nanoparticle preparation, and the like. The invention emphasizes the utilization of the advantages of multiple synergism and multiple targeting of nanometer carrier combination technology. After large-scale production, the production cost is greatly reduced; the product quality is greatly improved; and the medicament targeting and sustained and controlled release performance are stronger. Both internal and external administration can be employed, and administration can be performed at four time periods respectively based on meridian flowing and human body qi-blood flowing rules. Film agents and transdermal agents can be prepared, respectively pasted at different parts of human body based on meridian flowing and human body qi-blood flowing rules, and directly absorbed through skin.

Description

A kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof

Technical field

The present invention relates to a kind of Actinolitum rounding mould assembly novel form technology of preparing, the invention still further relates to a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof.

Background technology

Chinese medicine decocting liquid compound recipe drug effect chemical reaction is too many because of chemical constituent; Temporarily also do not disclosed its mysterious veil; But some mysterious black box drug actions are just ensconced in the Chinese medicine decocting liquid in the Chinese medicinal formulae, can not ask Chinese medicine westernization, the modernization of Chinese medicine simply most and only use monomer and effective site.The Chinese medicine water drug-decocting concentrating liquid could not be given it up! When the Chinese medicinal formulae water decocts; Because prescription closes chemical environment complicated in high temperature and the solution when frying in shallow oil; Reaction such as complexation, hydrolysis, oxidation, reduction between intrinsic material possibly take place in solution; Thereby some novel substance that did not have originally in the generation solution, these novel substances produce drug actions such as potentiation, attenuation or modification to full side.New component forms the research of mechanism, stability and drug effect thereof in the reinforcement Chinese medicinal formulae decocting liquid; To improving Chinese medicine compound and new drug level; Progressively dwindle Chinese medicine compound and new Chinese medicine and international gap; Crucial meaning is arranged, also increased new way and new source simultaneously for the research and development new Chinese medicine.

China's drug control relevant laws and regulations regulation changes dosage form and manages as new drug research.The backwardness of preparation level not only influences the performance of curative effect of medication; And cause the medicine added value low; Directly influencing the market competition and industrial economy benefit, is to cause China's medical industry product quantity to occupy prostatitis, the world and the output value only is equivalent to the one of the main reasons of one or two transnational drugmaker.

New drug, novel form exploitation level can embody the economy and the technical strength of the medical industry of a country.China's oral formulations accounts for 2/3 of various whole body drug-delivery preparations, and accelerating development and promoting oral sustained-release preparation is the work that current urgent need will be done.

The Actinolitum circle comes from " Song's formulary of peaceful benevolent dispensary ".The side is by two liang of Actinolitum (steeping in wine is partly said, carefully ground), Fructus Evodiae (soup is washed seven times, roasting, little stir-fry) three minutes, and Radix Rehmanniae Preparata one or two, Radix Achyranthis Bidentatae (going Seedling, steeping in wine, roasting), universe Rhizoma Zingiberis Recens (big gun), the Rhizoma Atractylodis Macrocephalae, each three is grouped into.Function cures mainly: it is cool to control the sub-deficiency of five ZANG-organs of married woman, and impairment caused by overstrain is excessive, and the wind and cold knot is fought, and infertility for a long time causes sterilization then and do not produce.These medicine clothes, accumulation of pathogenic cold is eliminated in big beneficial uterus.

Actinolitum:

Actinolitum is the crystalline schist of typical contact metamorphism formation and the contact zones of igneous rock.Sometimes also occur in the crystalline schist of metamorphism formation.Actinolitum is mineral common in the skarn, with symbiosis such as the tremolite, allochites.Actinolitic composition is that (wherein: FeO 6～13% for Mg, Fe++) 5 (Si4O11) 2 (OH) 2, and CaO 13.8%, and MgO 24.6%, and SiO2 58.8%, and H2O 2.8% for Ca2.(Mg, Fe2+) 5 [Si4O11] 2 (OH) 2 (tremolite) still contain a small amount of calcite or have hornblend concurrently and chlorite (aluminosilicate that contains magnesium ferrum aluminum) etc. the hydroxyl silicate Ga2 of main calcic, magnesium, ferrum.In addition, Actinolitum also is the essential mineral in some schist and the hydrothermal alteration basic volcanic rocks, with Talcum, chlorite symbiosis.Nature and flavor are salty, temperature.Return through kidney channel.The effect warming the kidney to invigorate YANG.Cure mainly part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels deficiency and coldness, the cold numbness of waist knee joint, impotence in male, woman's cold womb, mass in the abdomen metrorrhagia.

The pharmacological action of Fructus Evodiae:

1. the effect to the central nervous system is mainly analgesic activity, and its analgesic composition is rutaecarpin, rutaecarpine, isoevodiamine and obaculactone.10% ethanol extraction of intravenous injection Fructus Evodiae can make rabbit body temperature raise, and also can improve the threshold value of the mouth limit muscle group contracture that electricity irritation rabbit tooth marrow causes, its action intensity and aminophenazone are suitable.Fructus Evodiae water decoction 5g/kg and 20g/kg all can significantly postpone the pain sensation response time, can keep not disappear in 2.5 hours.Oral Fructus Evodiae has the town to tell effect, and with Rhizoma Zingiberis Recens clothes together, town's effect of telling can be reinforced.But also have report to point out, Fructus Evodiae decoct and acetone extractum are irritated stomach to dog respectively, the vomiting of dog due to 4% copper sulfate is not all had the town tell effect.

2. the effect evodol-water extract 0.03-0.24g/kg to cardiovascular system produces dependency pressor effect and the contractility that improves diaphragm for the quiet notes of anesthetized cat, but triethylammonium tetrakis can not antagonism.Also causing for clear-headed rats by intraperitoneal injection boosts.The both sides nephrectomy, phentolamine or gains in depth of comprehension Andu significantly reduce its boosting.Experiment shows: Fructus Evodiae decoct, electuary and distillate; Quiet notes and filling stomach all have remarkable hypotensive effect, and dose dependent is arranged, and the blood pressure lowering persistent period is longer; Generally reach more than 3 hours; The not obvious heart rate that influences during blood pressure lowering, but intramuscular injection then hypotensive effect very a little less than, experimental renal hypertension dog and normal rabbit are also had hypotensive effect.The Radix Glycyrrhizae decoct can make the hypotensive effect forfeiture of Fructus Evodiae.Fructus Evodiae does not have the blocking-up effect to neuroganglion, but the booster reaction that can cause antiadrenergic drug, norepinephrine, pituitrin.Have report to think, the evodol water extract produces through excited alpha-receptor and beta-receptor cardiovascular effect.Data shows: the hypotensive effect of Fructus Evodiae produces through various active composition, number of mechanisms.The hypotensive effect of Fructus Evodiae is relevant with the expansion peripheral blood vessel; Because of diphenhydramine can be cancelled its hypotensive effect, so also maybe be relevant with histamine.But it is irrelevant with cholinergic nerve and receptor thereof.Dehydroevodiamine is one of antihypertensive compositions, and it has the blood vessel dilating effect, in blood pressure lowering, and decreased heart rate, the effect that reduces diastolic pressure is better than systolic pressure; Because indometacin can part, Quadrafos can more fully cancel its hypotensive effect, the prompting hypotensive effect synthesizes relevant with prostaglandin.Demethylcoclaurine also is an antihypertensive compositions, and its blood pressure lowering increases heart rate simultaneously and reduces peripheral vascular resistance, and this effect can be blocked by propranolol, explains that its hypotensive effect is relevant with excited beta-receptor.

3. the effect research to digestive system shows: evodine contained in the Fructus Evodiae is an amaroid, and the bitterness digestion promoting function is arranged, and its contained volatile oil has fragrant digestion promoting function again.The methanolic extract of Fructus Evodiae has the effect of Chinese People's Anti-Japanese Military and Political College's Mus water logging stress ulcer; Water decoction also has anti-hydrochloric acid gastric ulcer and indometacin adds the effect of ethanol gastric ulcer, and water logging irritability and ligation pylorus ulcer are had the tendency that suppresses formation.Activity has two-way function to Fructus Evodiae to rat small intestine in vitro, and is excited during low concentration, suppresses spontaneous contraction movement during high concentration, can antagonism nicotine, physostigmine, acetylcholine, histamine, barium chloride, phentolamine, reserpine be to the excitation of rat small intestine in vitro; Also can resist six hydrocarbon quaternary amines, atropine and epinephrine inhibitory action to rat small intestine in vitro, but can not the antagonism diphenhydramine, papaverine, verapamil, methadone be to the inhibitory action of isolated rabbit small intestinal.Show that excited intestinal tube effect of Fructus Evodiae and acetylcholine nerve and M-cholinoceptor are irrelevant, its inhibitory action maybe be not too big with adrenergic nerve and alpha-receptor relation, and maybe be relevant with direct excited beta-receptor.The Fructus Evodiae water decoction is given mice oral (20g/kg), can significantly reduce the large intestine irritative diarrhea number of times that Folium Sennae causes; The small intestinal irritative diarrhea number of times that Oleum Ricini is caused also has the tendency of minimizing.The slow down gastrointestinal propulsion of normal mouse of Fructus Evodiae, also can the antagonism morphine or atropine to the inhibition of the gastrointestinal propulsion of mice, the prompting Fructus Evodiae helps regulating the intestinal effect of body to the two-way function of intestinal tube.Diarrhoea and lienteric diarrhea to due to the gastrointestinal dysfunction are also effective.Fructus Evodiae can make intestinal tube excited, and its contained cGMP possibly participate in the intestinal tube activity.The active effect of the excited intestinal tube of Fructus Evodiae maybe through choline-like, histamine appearance, the effect of antiadrenergic drug appearance or through wherein two or through one of them realization.

4. the sympathetic composition oxedrine of the plan in the effect Fructus Evodiae of uterine smooth muscle there is lax isolated uterine effect, removes the then excited rat uterus of residual liquid of intending sympathetic composition and the relexation that can resist oxedrine.The composition in its excited uterus is dehydroevodiamine, rutaecarpine and rutamine.Dehydroevodiamine possibly be the 5-hydroxytryptamine receptor agonist, and its excited uterus interaction energy can not be blocked by atropine by the blocking-up of dimethyl ergometrine.

5. other effect Fructus Evodiae decocts have stronger inhibitory action to vibrio cholera; To trichophyton, Trichophyton concentricunm, permitted dermatophytess such as blue achorion, Du's big belly microspore tinea bacterium difficult to understand, rust budlet spore tinea bacterium, ulotrichy budlet spore tinea bacterium, Gypsum Fibrosum appearance budlet spore tinea bacterium, epidermophyton inguinale, star-shaped nocardia inhibitory action in various degree all arranged.Fructus Evodiae water extract and 50% methanolic extract have the anti-caries effect.Evoxine has antivirus action to the mice that infects Colombia SK strain virus.Experiment in vitro, Fructus Evodiae decoct and alcohol, ether extract can be killed ascaris suum, Lumbricus and Hirudo external.The Fructus Evodiae decoct gives that rabbit is oral to have a diuresis; Healthy subjects is oral also to have diuresis.The diuresis composition is rutaecarpin and rutaecarpine.

The pharmacological action of Radix Rehmanniae Preparata:

Comparison shows that about Radix Rehmanniae Preparata and Radix Rehmanniae drug effect to post-thrombotic syndrome effect in the blood vessel: in the thick Radix Rehmanniae Preparata of home-made Fel Sus domestica shape can strong inhibition liver hemorrhagic necrosis kitchen range and simple necrosis.And a little less than the effect of Radix Rehmanniae Preparata antithrombase.Application of fiber fibrillarin flat band method is inquired into the activation to fibrinolytic system through the plasminogen activation, find that Radix Rehmanniae Preparata has activation, and the Radix Rehmanniae does not have this effect.Also there is report to think, before and after the Radix Rehmanniae parch to black anastalsis is arranged all, and anastalsis do not strengthen after the Radix Rehmanniae charcoal processing.Decocting liquid haemostatic effect to Radix Rehmanniae, Radix Rehmanniae Preparata, fresh rehmannia charcoal, charred RADIX REHMANNIAE is analyzed, as a result there was no significant difference.Experiment is found: bosom celebrating Radix Rehmanniae Preparata water decoction is irritated clothes; Can make losing weight of hyperthyroidism type deficiency of YIN rat be able to alleviate; 24 hours amounts of drinking water and urine amount obviously reduce, and blood plasma T3, T4 concentration level are significantly improved (being that T3 reduces, T4 raises) and AD (aldosterone in the blood plasma) level obviously raises.Prove that it truly has stronger nourishing yin effect.And think that tentatively the effect of Radix Rehmanniae Preparata enriching yin and nourishing kidney is with to improve in the body AD level relevant.The Radix Rehmanniae Preparata water decoction is given mouse gavaging, can obviously increase the activity of glutathion peroxidase (GSH-Px) in the animal serum; Reduce the content of lipid peroxide in the serum.Can make the activity of superoxide dismutase in the blood (SOD) that rising is to a certain degree arranged, but not have statistical meaning.Catalase activity in the blood there is not influence.Protein metabolism has certain effect to Radix Rehmanniae Preparata to rat part internal organs.Radix Rehmanniae Preparata is oral to have the mitotic effect of the epithelial cell of inhibition.Experiment shows: but with the Radix Rehmanniae Preparata be principal agent LIUWEI DIHUANG TANG to normal mouse except that weight increase, prolong the swimming time, outside the physical strength reinforcing; Can also reduce the rate of bringing out of the mice model of forestomach scale cancer that nitrososarcosine-ethyl-ester causes; Make the animal spleen lymphatic nodule germinal center active proliferation of accepting chemical carcinogen; Initial stage at the inoculation transplanted tumor can strengthen the huge activate the phagocytic capacity of biting system of monokaryon; The ratio of albumin and globulin in the raising tumor animal blood is like the time-to-live that can prolong tumor animal.

The pharmacological action of Radix Achyranthis Bidentatae:

1. the effect Radix Achyranthis Bidentatae alcohol extract to cardiovascular system all has certain inhibitory action to isolated frog heart and anesthetized cat at systemic heart.Decoct also has the obvious suppression effect to the anesthetized dog cardiac muscle.Radix Achyranthis Bidentatae decoct or alcohol extract are given intravenous injections such as anesthetized dog, cat, rabbit; Of short duration hypotensive effect is all arranged, and excited with breathing during blood pressure drops, nothing tolerates phenomenon rapidly; The mechanism of hypotensive effect mainly is the release of histamine, also suppresses relevant with the expansion peripheral blood vessel with heart simultaneously.The Radix Achyranthis Bidentatae decocting liquid is injected to rabbit vein, can bring high blood pressure down immediately, go up again afterwards, but level before in a hour, being lower than administration all the time.The Radix Achyranthis Bidentatae fluid extract is used for animals such as Canis familiaris L., rabbit and Bufo siccus, make the blood pressure drops effect, but the time is not long; Counter after the recovery have an effect that blood pressure was once slightly being risen.Also have report to point out, from the coarse wool Radix Achyranthis Bidentatae, separate obtaining one and contain two kinds of alkaloidal mixture, it can make anaesthetized dog blood pressure raise, and breathes excitedly, and heart contraction is strengthened.Radix Achyranthis Bidentatae still has the rat of reduction whole blood viscosity, packed cell volume, the exponential effect of red blood cell condensation, and can prolong rats prothrombin time and blood plasma recalcification time.Still have experiment to show: Radix Achyranthis Bidentatae can make the animal blood viscosity degradation, and blood flow quickens; The animal blood clotting is accelerated, can be avoided or alleviate the internal hemorrhage that causes because of the blood vessel breakage.

2. no matter excited uterus and antifertility action Radix Achyranthis Bidentatae fluid extract or decoct are pregnant to the isolated rabbit uterus, unpregnancy all has excitation.To shrinking unable mice isolated uterine, then make to shrink and strengthen.Unpregnancy uterus to cat is the effect of relaxing, and strong contraction is then taken place in pregnant uterus.The total Saponin of Radix Achyranthis Bidentatae can make the rat uterus shrinkage amplitude increase, and frequency is accelerated, and tension force increases, and the uterine contraction area enlarges markedly before than administration.The total Saponin of Radix Achyranthis Bidentatae is concentration dependence excitation: 0.5mg/ml to the isolated rat uterus can cause the maximum collapse in uterus; When concentration increased to 1.0mg/ml, the corresponding increase of its contraction intensity was not obvious, only showed as the uterus area and shrank the peak reach, and shorten incubation period.All there is appreciable stimulating action in isolated rat uterus under the different physiological conditions, but to a little less than the effect very of children uterus in age, the strongest to pregnant uterus effect in evening.Experiment shows: the total Saponin of Radix Achyranthis Bidentatae was given behind the rabbit topical in 1～4 minute, unpregnancy and in pregnant rabbit in the body uterus all intensive contraction can appear, excitation generally continues effect in 25 minutes and weakens gradually.Have report to point out, no matter be in vivo or external after the indometacin pretreatment, all obviously weaken of the excitation of the total Saponin of Radix Achyranthis Bidentatae to the isolated rat uterus.The total Saponin of prompting Radix Achyranthis Bidentatae possibly be excited rat uterus through the release of PG.The experiment proof: the effect of the excited rat uterus of the total Saponin of Radix Achyranthis Bidentatae and the release of acetylcholine are irrelevant.Radix Achyranthis Bidentatae benzene extractives 50～80mg/kg, chloroform extract 80～120mg/kg all have obvious antifertility and antiearly pregnancy effect, and the former still has obvious anti-implantation effect.The total Saponin of Radix Achyranthis Bidentatae has significant antifertility action to mouse stomach, and its effect strengthens with the increase of dosage; And tangible anti-implantation effect arranged.But the rat oral gavage administration is not then had the antifertility effect, also do not have the induced abortion effect.There is report to point out that ecdysterone is the effective ingredient of Radix Achyranthis Bidentatae antifertility.

3. antiinflammatory, analgesic activity Radix Achyranthis Bidentatae medicated wine have obvious therapeutic action to rat formaldehyde property swelling of the feet.Radix Achyranthis 200% extracting solution has stronger resist inflammation on repercussive function, but this effect is not to be through due to the adrenal cortex release 17-hydroxy-11-dehydrocorticosterone.Have report to think that the anti-inflammation detumescence mechanism of Radix Achyranthis Bidentatae is the human body immunity improving function, the activation mouse macrophage is united to the phagocytosis of antibacterial and blood vessel dilating, improvement circulation, is promoted inflammatory lesion absorption etc.Radix Achyranthis Bidentatae has analgesic activity, and Radix Achyranthis Bidentatae decoct lumbar injection can suppress " writhing response " due to antimony potassium tartrate or the acetic acid.Experiment shows: it is best that Radix Achyranthis Bidentatae analgesic effect is produced in Henan, and injecting can the appearance effect in 10 minutes.

4. gastrointestinal effect zoopery is proved: Radix Achyranthis Bidentatae is given anesthetized dog, anesthesia or normal rabbit intravenous injection, can make its stomach motion after of short duration excitement, transfer inhibition to.Radix Achyranthis Bidentatae has inhibitory action to the mice intestine in vitro.The Cavia porcellus intestinal tube there is the reinforcement contraction.

5. other effect Radix Achyranthis Bidentatae decocts or alcohol extract have slight diuresis for anesthetized rabbit or dog intravenous injection.Radix Achyranthis Bidentatae decoct lumbar injection can not resist because the mice convulsion that strychnine, pentetrazole and caffeine cause, but after injection half an hour, animal appearance slightly is tired and movable and weakens, center of origin suppresses phenomenon.Ecdysterone in the Radix Achyranthis Bidentatae does not have influence to euglycemia, but the hyperglycemia reduction that glucagon, AIS, alloxan etc. are caused, and the liver function of improvement is arranged, reduce the effect of serum cholesterol.Contain insecticide steroidal metamorphosis hormone in the Radix Achyranthis Bidentatae, can promote protein synthesis.Behind mouse peritoneal injection or oral ecdysterone or inokosterone, the amount by the aminoacid synthetic protein is significantly increased, its effect is similar with the effect of protein anabolic hormone 4-chlorotestosterone by force.Radix Achyranthis Bidentatae still has the anti-ageing effect of lengthening the life.

The pharmacological action of Rhizoma Zingiberis:

Rhizoma Zingiberis contains volatile oil, and main component is a zingiberene.The Rhizoma Zingiberis acrid in the mouth, hot in nature.Return spleen, stomach, the heart, lung meridian.Rhizoma Zingiberis has warming spleen and stomach for dispelling cold, and recuperating depleted YANG is promoted blood circulation, the effect of dampness expectorant.The Rhizoma Zingiberis pharmacological action is following:

1. to the influence of digestive system: Rhizoma Zingiberis adds ethanol property, salt acidity and ligation pylorus gastric ulcer to stress ulcer, indomethacin all has obvious inhibitory action.Rhizoma Zingiberis contains armaticity volatile oil, and digestive tract is had slight stimulation, intestinal tension force, the rhythm and pace of moving things and wriggling is strengthened, thereby promote the gastrointestinal digestive function.Irritate clothes Rhizoma Zingiberis Recens decoct to dog and can make gastric secretion and free acid secretion increase, the activity doctor of lipolytic enzyme | learn education network and collect the arrangement reinforcement.Rhizoma Zingiberis can also strengthen salivation, strengthens the eupepsy to starch.Rhizoma Zingiberis extractum can suppress the emetic action of copper sulfate, but to pigeon by Folium Digitalis Purpureae, the vomiting unrestraint effect that dog is brought out by apomorphine, tell and acts in prompting Rhizoma Zingiberis town is tip property.The mixture of zingiberone and ginger ketenes is the effective ingredient that tell in the town.

2. to the influence of cardiovascular system: Rhizoma Zingiberis can make guinea-pig heart room autonomic movement strengthen, and its heart tonifying composition is gingerol and ginger ketenes.Contain the Rhizoma Zingiberis rat blood serum and the better protect effect is arranged cultivating the scarce sugar property damage of neonatal rat myocardial cell anoxia.The shogaol intravenous injection can make rat blood pressure be three phasic properties and change.Rhizoma Zingiberis Recens volatile oil, gingerol and shogaol can distend the blood vessels, blood circulation promoting.Shogaol can suppress the contraction of norepinephrine (NA) to mesenteric vein.

3. the water of Rhizoma Zingiberis, ether extract all have tangible antiinflammatory action; All can suppress the doctor that ear swelling that xylene causes and carrageenin cause | learn education network and collect the arrangement rat paw edema; The rare ketone of Rhizoma Zingiberis Recens can obviously suppress histamine and acetic acid induced mice capillary permeability increases, and suppresses granulation hyperplasia.Rhizoma Zingiberis water extract, Rhizoma Zingiberis volatile oil or Rhizoma Zingiberis phenolic acid property position, the antiphlogistic while can significantly be reduced ascorbic content among the rat adrenal gland, explains that the antiinflammatory action of Rhizoma Zingiberis possibly produce through promoting adrenocortical function.

4. Rhizoma Zingiberis ether extract, water extract all have analgesic activity, can reduce acetic acid and cause the mouse writhing reaction times, and be dose-effect relationship.Simultaneously can also prolong the mice thermostimulation response latency.

5. antithrombotic: the Rhizoma Zingiberis water extract has the obvious suppression effect to ADP, the inductive platelet aggregation of collagenase, postpones experimental thrombosis and forms, and ginger ketenes generation also active to tame rabbit platelet Cycloxygenase and TXA2 has inhibitory action.Rhizoma Zingiberis volatile oil also has antithrombotic effect, and can obviously prolong the kaolin APFI.

The pharmacological action of the Rhizoma Atractylodis Macrocephalae:

Rhizoma Atractylodis Macrocephalae property is bitter, sweet, temperature.Return spleen, stomach warp.Have invigorating the spleen and benefiting QI, the dampness diuretic, hidroschesis, antiabortive.Be used for insufficiency of the spleen lack of appetite, abdominal distention is had loose bowels, the phlegm retention vertigo and palpitation, and edema, spontaneous perspiration, invigorating the spleen and benefiting QI, the dampness diuretic, hidroschesis, antiabortive etc.Effects such as the Rhizoma Atractylodis Macrocephalae has adjustment gastrointestinal motility function, antiulcer, protects the liver, enhancing human body immunity function, anti-stress, enhancing hemopoietic function; Its dampness diuretic effect is relevant with diuresis; And antiabortive effect is relevant with the effect of inhibition uterine contraction.The Rhizoma Atractylodis Macrocephalae also has effects such as antioxidation, slow down aging, blood sugar lowering, anticoagulation, antitumor.Concrete pharmacological action is following:

The Rhizoma Atractylodis Macrocephalae has adjustment gastrointestinal motility function.Rhizoma Atractylodis Macrocephalae decocting liquid has excitation to gastrointestinal motility, and Rhizoma Atractylodis Macrocephalae volatile oil then has inhibitory action.The autonomic movement of Rhizoma Atractylodis Macrocephalae volatile oil inhibition intestinal tube and the effect of antagonism barium chloride are stronger, and the effect of the juniper camphor antagonism acetylcholine in the volatile oil is stronger.The acetone extract gastric infusion of the Rhizoma Atractylodis Macrocephalae has the obvious suppression effect to rat stomach mucosa injury due to hydrochloric acid-ethanol.Through duodenal administration pylorus ligation rat gastric secretion there is inhibitory action, reduces gastric acidity, reduce gastric acid and pepsic output.Mouse stomach Rhizoma Atractylodis Macrocephalae decocting liquid can be prevented and treated the hepatic injury due to the carbon tetrachloride, alleviates hepatic glycogen minimizing and hepatocellular degeneration necrosis, promotes hepatocyte to increase, and the ALT of rising is descended.The Rhizoma Atractylodis Macrocephalae can significantly strengthen the ability of leukocytes phagocytic staphylococcus aureus.Rhizoma Atractylodis polysaccharide has the effect of recovery to lymphocytic propagation function, and improves the survival rate of immunosuppressed mice spleen cell In vitro culture, prolongs lymphocyte life span, corrects T subsets distribution disturbance state, and low IL-2 level is significantly improved.The Rhizoma Atractylodis Macrocephalae has the effect of resisting fatigue and adrenal cortex reinforcing function.The Rhizoma Atractylodis Macrocephalae has the mouse red blood cell of promotion hemoposieis.Mouse subcutaneous injection Rhizoma Atractylodis Macrocephalae decocting liquid 3 days has remarkable promotion hemopoietic progenitor cell of red blood cell line nucleus formation.Rat, rabbit, irritate stomach or intravenous injection Rhizoma Atractylodis Macrocephalae decocting liquid or fluid extract greatly, have obvious and persistent diuresis, can promote the especially discharge of sodium of electrolyte.The diuresis mechanism of the Rhizoma Atractylodis Macrocephalae possibly heavily absorb with the inhibition electrolyte, and the drainage that increases Na+, K+, CI-is relevant.The antiabortive effect of the Rhizoma Atractylodis Macrocephalae is relevant with its inhibition uterine contraction effect.The alcohol extract of the Rhizoma Atractylodis Macrocephalae and ligroin extraction shrink the spontaneity of unpregnancy mice isolated uterine; And the uteri excitation property contraction that oxytocin, Herba Leonuri cause all presented remarkable inhibitory action; And the inhibitory action enhancing with the drug level increase, the amount effect relationship.Rhizoma Atractylodis Macrocephalae Wheat Protein.Can effectively suppress lipid peroxidation, reduce the content of organizing MDA, avoid the destruction of harmful substance, can resist mice and HRBC's autoxidation haemolysis the histiocyte 26S Proteasome Structure and Function.The Rhizoma Atractylodis Macrocephalae has the effect that delays the aging of Aged Mice kidney, and the kidney structure of aged mouse is had clear improvement.Rabbit is irritated clothes Rhizoma Atractylodis Macrocephalae decocting liquid to be had the oxidation utilization of glucose in the acceleration bodies and hypoglycemic activity is arranged.Its prothrombin time significant prolongation behind the rat oral gavage Rhizoma Atractylodis Macrocephalae decocting liquid.After healthy subjects is taken Rhizoma Atractylodis Macrocephalae decocting liquid or alcohol leaching liquid, the equal significant prolongation of its prothrombin time and clotting time.The Rhizoma Atractylodis Macrocephalae has cytotoxicity to oncocyte, can reduce the rate of increase of oncocyte, lowers the aggressive of tumor tissue, improves the ability of body antitumor reaction.Rhizoma Atractylodis Macrocephalae volatile oil has inhibitory action to mice ehrlich carcinoma, lymphosarcoma ascitic type, the esophageal carcinoma (Ecal09), sarcoma 180 etc.

Novelty and breakthrough that the present invention has essence are to have found out the key point that Actinolitum circle modern Chinese medicine novel form Chinese and western medicine theory combines; The present invention will in time fill up the blank of researching and developing " Actinolitum rounding mould assembly novel form " field both at home and abroad in utilization " nano-carrier GC-MS " 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 through international one-level novelty assessment report and patent retrieval.Utilize domestic and international data base to carry out update search; Comprehensive domestic and foreign literature is read, is analyzed contrast and obtains to draw a conclusion: " the integrated novel form of GC-MS research and development Nano medication " project; Its innovative point: nanosphere, nanocapsule, polymer micelle, solid ester matter nanoparticle, magnetic nano particle, immune nano grain, nano-emulsion, suspensoid, vesicle, pharmacosomes, microcapsule, nanoparticle, millimicro ball, the millimicro that 1) adopts the Chinese medicine nano-powder be rich in trace element, medicine monomer, effective site, effective part group, Chinese medical concrete, water drug-decocting concentrating liquid etc. to go out the different-grain diameter size with the different pharmaceutical preparing carriers assisted etc., and mixing is respectively charged into to unite simultaneously in soft, the hard capsule and uses 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 then; 2) utilization nano-carrier GC-MS 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 public reported in the document at home, this Project Comprehensive technical characterstic has certain novelty and novelty.Science and technology is looked into new numbering: 200921c0704948.

Further: this integrated novel form technology of preparing is to have integrated the advantage separately of the traditional Chinese medical science, doctor trained in Western medicine; With the organic conception of theory of Chinese medical science and collaborative idea and the determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs of paying attention between medicine is the overall strategy tactical thinking; In conjunction with modern western pharmacology, pharmacokinetics, toxicology, pharmaceutics scheduling theory; Pay attention to the effectiveness and the therapeutic effect of certified Chinese medicine one matter monomer treatment, pay attention to Chinese medicine active substance, effective site and active substance crowd the treatment mass action that disease played.Pay attention to the contained trace element of Chinese medicine to the treatment assosting effect that disease played.The effective ingredient of the used Chinese medicine of this Chinese medicine compound is clear and definite, and medicine effect has obtained admitting of modern medicine.Pay attention to utilization nano-carrier GC-MS development modern Chinese medicine.These will promote the development of China's Chinese medicine industry.

Summary of the invention:

The object of the invention is exactly the problems referred to above that exist in the prior art in order to solve, and a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof are provided.

The object of the invention is realized through following technical scheme:

A kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof, wherein: this integrated novel form raw materials of effective components and weight proportion---2 parts of Actinolitum, 3 parts of Fructus Evodiaes, 1 part of Radix Rehmanniae Preparata, 3 parts of Radix Achyranthis Bidentataes, 3 parts of universe Rhizoma Zingiberis Recens, 3 parts of the Rhizoma Atractylodis Macrocephalaes.

Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, selenium.Above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof; Wherein: medicine is become medicine support material medicine with preparing carriers; Crude drug can be one or more combinations in nanoparticle, nanoparticle, micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, the microcapsule etc., and can as required one or more be mixed.Described protection domain is not only the said medicine support material medicine in the said scope, is also included within to prepare on its basis or add the curative effect that other do not influence its disease of controlling, and just makes the pharmaceutical carrier crude drug of its better efficacy.Further; Above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof; Wherein: the drug carrier material that this novel form is selected for use, activating agent, help excipient substances such as Emulsion, dispersant be gelatin, albumin, starch and derivant thereof, alginate, beta-schardinger dextrin-, protein, chitosan and derivant thereof, lactose, hydroxypropyl emthylcellulose, ethyl cellulose, cellulose acetate phthalate, metering system acetate, polylactic acid, cyanoacrylate, semisolid poe, triglyceride (as in three stearic acid, three Palmic acids, three lauric acids, three oleic acid etc., the glyceride of LCFA), in glyceride (, containing the synthetic glyceride of list, two, triglyceride), cholesterol, Polyethylene Glycol, microcrystalline wax, whale ester type waxes, erythrocyte, Montmorillonitum, tea powder etc. one or more like glyceryl monostearate.Described excipient substance is not only the said medicine adjuvant in the said 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; Above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof; Wherein: said integrated novel form adopts medicament nano powder body, micro-powder, medicine monomer, effective ingredient, effective site, active substance crowd, Chinese medical concrete, water drug-decocting concentrating liquid and different drug adjuvant, pharmaceutical carrier to unite use according to indexs such as the pharmacology of traditional Chinese medical science global theory, compatibility theory and medicine, drug effect, medicine generation, toxicitys.And can mix its one or more according to the preparation needs.

Again further; Above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof, wherein: the integrated novel form end product that finally can form is: tablet, powder, suppository, stick, granule, soft capsule, hard capsule, effervescent, drop pill, aerosol, unguentum, oral solution, slow releasing tablet, controlled release tablet.

A kind of Actinolitum rounding mould assembly novel form technology of preparing 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 powder and micron, subsequent use.

Step 2: get 30%--90% alcohol-water solution mixed soaking 1-2 days that 60% Actinolitum, Fructus Evodiae, Radix Rehmanniae Preparata powder and micron doubly measure with 6-12; Reflux, extract, 3 times; Extract water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol gets extract with subsequent use.

Step 3: get 60% Radix Achyranthis Bidentatae, universe Rhizoma Zingiberis Recens, Rhizoma Atractylodis Macrocephalae powder and micron; Adopt the ultrasonic dispersing extraction equipment of independent research to disperse respectively to extract; Ultrasonic power is: 800W-3000W, supersonic frequency: 28KHz--120KHz, to pulverize extraction time be 10-100 minute, extract with subsequent use.

Step 4: with step 2, step 3 gained Chinese medicine extract, adopt the nanon ball-mill of independent research to grind 4-16 hour, get particle size distribution and be the nano powder of 50-1000 nanometer, subsequent use.

Step 5: get each Chinese medicine powder and micron of 40%, boiled 3 times with the traditional Chinese medicine extracting machine decocting after being soaked in water two hours, decocting liquid merges and filters, and filtrating concentrates, Chinese medical concrete or water drug-decocting concentrating liquid with subsequent use.

Step 6: with step 2, step 3, step 4 gained Chinese medicine extract, nano powder as required with and the different property of medicine, pharmacological actions; Can adopt technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to prepare respectively, obtain medicine materials such as different drug monomer, effective site, active substance crowd.

Step 7: above-mentioned gained medicine material is adopted the different drug adjuvant, and " preparation part of standards standard was with " requirement of version Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " in 2005 in waiting adopts the high pressure breast to spare method respectively in the Chinese pharmacopoeia by version in 2010; Inclusion technique; Solid state technology; Polishing; Solvent-fusion method; Squeezing and pressing method; Complex coacervation; Emulsion-crosslinking method; The polymerization dispersion method; Fusion method; Technology such as freeze-drying are prepared into nanoparticle; Nanoparticle; The micron liposome; Nanometer liposome; Solid lipid nanoparticle; Nanometer polymer micelle; Pharmacosomes; Nano-emulsion; Lipid microsphere; Microcapsule; Microemulsion; Lipid liquid; Nanometer film; Nanometer suspension liquid; Crude drug such as microcapsule.The crude drug particle diameter is between 10 nanometers-10 micron.

Step 8: " preparation part of standards code requirement in the Chinese pharmacopoeia was got in the crude drug such as step 5 gained Chinese medical concrete or water drug-decocting concentrating liquid and step 7 gained nanoparticle, liposome, nano-emulsion, microcapsule one or more and is mixed by formula proportion by version in 2010.

Step 9: in GMP10000 level toilet, with above-mentioned mixed raw materials medicine adopt the fully-automatic capsule filling machine respectively fill become hard capsule and soft capsule.Also can by version in 2010 " Chinese pharmacopoeia related preparations standard criterion is processed the above-mentioned end product of other type.

Step 10: the end product of processing 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.

Above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof; Wherein: the Chinese medicine of using in said step 1, step 2, the step 3 is pulverized and method for distilling; Described protection domain 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, breaking method, method for distilling and the technology of more advanced, more environmental protection.

Further; Above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof, wherein: crude drug such as the dissimilar nanoparticle that employing different pharmaceutical adjuvant is prepared in the medicine monomer in the said step 6, active substance, effective site technology of preparing and the said step 7, nano-emulsion.The described protection domain of this claim is not only described technology of preparing and method, as required, be also included within add on its basis or use other better effects if, more economical, upgrade, the method for preparing and the technology of more advanced, more environmental protection.

Further; Above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof; Wherein: its key point 1 is different utilization nano-carrier GC-MSs different according to the particle diameter of crude drug and the property of medicine, can produce the gentle controlled capability of different targeting property.

Again further, above-mentioned a kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof, wherein: its key point 2 is to develop simultaneously by interior external administration, can take four time periods respectively by midnight-noon and ebb-flow doctrine, energy and blood of human body flowing law.Also can be prepared into membrane, transdermal agent is attached to the human body different parts respectively by the energy and blood of human body flowing law, can directly absorb through skin.

The outstanding substantive distinguishing features and the obvious improvement of technical scheme 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 Actinolitum circle Chinese and western medicine theory combines; The present invention will in time fill up the blank of researching and developing " Actinolitum rounding mould assembly novel form " field both at home and abroad in utilization " nano-carrier GC-MS " with theory of integrated Chinese and western medicine; Product has the targeting advantage such as wide that distributes, and does not have identical or similar bibliographical information both at home and abroad.Show substantive progressive and novelty of the present invention through 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, is analyzed contrast and obtains to draw a conclusion: " the integrated novel form of GC-MS research and development Nano medication " project; Its innovative point: nanosphere, nanocapsule, polymer micelle, solid ester matter nanoparticle, magnetic nano particle, immune nano grain, nano-emulsion, suspensoid, vesicle, pharmacosomes, microcapsule, nanoparticle, millimicro ball, the millimicro that 1) adopts the Chinese medicine nano-powder be rich in trace element, medicine monomer, effective site, effective part group, Chinese medical concrete, water drug-decocting concentrating liquid etc. to go out the different-grain diameter size with the different pharmaceutical preparing carriers assisted etc., and mixing is respectively charged into to unite simultaneously in soft, the hard capsule and uses 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 then; 2) utilization nano-carrier GC-MS 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 public reported in the document at home, this Project Comprehensive technical characterstic has certain novelty and novelty.Science and technology is looked into new numbering: 200921c0704948.

Further; This integrated novel form technology of preparing and production method thereof are to have integrated the advantage separately of the traditional Chinese medical science, doctor trained in Western medicine; With the organic conception of theory of Chinese medical science and collaborative idea and the determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs of paying attention between medicine is the overall strategy tactical thinking; In conjunction with modern western pharmacology, pharmacokinetics, toxicology, pharmaceutics scheduling theory; Pay attention to the effectiveness and the therapeutic effect of certified Chinese medicine one matter monomer treatment, pay attention to Chinese medicine active substance, effective site and active substance crowd the treatment assosting effect that disease played.Pay attention to the contained trace element of Chinese medicine to the treatment assosting effect that disease played.The effective ingredient of the used Chinese medicine of this Chinese medicine compound is clear and definite, and medicine effect has obtained admitting of modern medicine.Pay attention to the different nano-carrier dosage form technologies of preparing of Chinese medicine and unite use.Be to adopt Chinese medicine crude drug nano-powder, monomer, effective site, effective part group, Chinese medicine concentrated extract, water drug-decocting concentrating liquid, nano-medicament carrier etc. to unite use on the compatibility.These various Chinese traditional powder particle diameter major parts of filling a prescription are the granule of 50～1000 nanometers.Adopting different nano-medicament carriers to be prepared into nanoparticle, nanosphere, nanocapsule, solid ester matter nanoparticle, nano-emulsion, vesicle, pharmacosomes, microcapsule, nanoparticle, millimicro ball, millimicro assists etc.Its particle size distribution is between 10 microns of 10 nanometers----.Theoretical according to difference, the difference of slow controlled release time and the traditional Chinese medical science monarch of pharmacology, targeting then, reasonable compatibility mixes, and is respectively charged among hard capsule and the soft capsule.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 property of the overall coordination therapeutical effect of this Chinese medicine compound novel form, slow controlled capability are stronger, and curative effect is more outstanding, and toxic and side effects still less.Multichip carrier and multiple medicines thing monomer etc. are united use, have broken through the traditional monarch compatibility theory of the traditional Chinese medical science, for the modern Chinese medicine development provides a practical effective novel form compatibility program.Be to have substantial technological innovation to break through.

The object of the invention, advantage and characteristics will make an explanation through the non-limitative illustration of following preferred embodiment.These embodiment only are the prominent examples of using technical scheme 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 requirement protection of the present invention.

The specific embodiment

A kind of Actinolitum rounding mould assembly novel form technology of preparing and production method thereof, its special feature is: processing the raw materials of effective components composition does by weight ratio---2 parts of Actinolitum, 3 parts of Fructus Evodiaes, 1 part of Radix Rehmanniae Preparata, 3 parts of Radix Achyranthis Bidentataes, 3 parts of universe Rhizoma Zingiberis Recens, 3 parts of the Rhizoma Atractylodis Macrocephalaes.

Further; Play the synergy of standing like the legs of a tripod on the Actinolitum rounding mould assembly new drug formulation compatibility of the present invention: 1, prepare nanometer, micro-powder, the bioavailability after strengthening Actinolitum circle curative effect and significantly improve prepared slices of Chinese crude drugs cell wall breaking with this with the prepared slices of Chinese crude drugs; 2, with Chinese medicine extract and select the 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 Actinolitum circle with this; 3, prepare Chinese medical concrete, water drug-decocting concentrating liquid with the prepared slices of Chinese crude drugs, strengthen the temporary transient unpredictable drug effect that reactions such as the unique complexation of Actinolitum circle Chinese medicine compound, hydrolysis, oxidation, reduction bring with this and keep and strengthened traditional Chinese medical science organic conception, monarch notion.More than three aspects associatings compatibility use; Different according to Nano medication particle diameter and character; Can reach effects such as many targeting, many collaborative, slow controlled releases, and play useful effect to strengthening the medicine pharmacologically active, effective ingredient pharmacological action effect is significantly higher than conventional formulation.

Production method of the present invention may further comprise the steps:

At first, get each prepared slices of Chinese crude drugs pretreatment, insert pulverizer after the weighing and be crushed to the 80-200 order, adopt supersonic airstream to be crushed to the 1-10 micron then, get different Chinese medicine powder and micron, subsequent use.Get 30%--90% alcohol-water solution mixed soaking 1-2 days that 60% Actinolitum, Fructus Evodiae, Radix Rehmanniae Preparata powder and micron doubly measure with 6-12; Reflux, extract, 3 times; Extract water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol gets extract with subsequent use.Get 60% Radix Achyranthis Bidentatae, universe Rhizoma Zingiberis Recens, Rhizoma Atractylodis Macrocephalae powder and micron; Adopt the ultrasonic dispersing extraction equipment of independent research to disperse respectively to extract; Ultrasonic power is: 800W-3000W, supersonic frequency: 28KHz--120KHz, extraction time are 10-100 minute, get extract with subsequent use.With above-mentioned gained Chinese medicine extract, adopt the nanon ball-mill of independent research to grind 4-16 hour, get particle size distribution and be the nano powder of 50 nanometers-1000 nanometer, subsequent use.Get each Chinese medicine powder and micron 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 filtrating concentrates, and gets Chinese medical concrete or water drug-decocting concentrating liquid with subsequent use.With above-mentioned gained Chinese medicine extract, nano powder as required with and the different property of medicine, pharmacological actions; Can adopt technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to prepare respectively, obtain medicine materials such as different drug monomer, effective site, active substance crowd.Above-mentioned gained medicine material is adopted different drug adjuvant and carrier, and " related preparations part of standards standard was with " requirement of version Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " in 2005 in waiting adopts the high pressure breast to spare method respectively in the Chinese pharmacopoeia by version in 2010; Inclusion technique; Solid state technology; Polishing; Solvent-fusion method; Squeezing and pressing method; Complex coacervation; Emulsion-crosslinking method; The polymerization dispersion method; Fusion method; Technology such as freeze-drying are prepared into nanoparticle; Nanoparticle; The micron liposome; Nanometer liposome; Solid lipid nanoparticle; Nanometer polymer micelle; Pharmacosomes; Nano-emulsion; Lipid microsphere; Microcapsule; Microemulsion; Lipid liquid; Nanometer film; Nanometer suspension liquid; Crude drug such as microcapsule.The crude drug particle size distribution of preparing is between 10 nanometers-10 micron." preparation part of standards code requirement in the Chinese pharmacopoeia was got in the crude drug such as above-mentioned gained Chinese medical concrete or water drug-decocting concentrating liquid and above-mentioned gained nanoparticle, liposome, nano-emulsion, microcapsule one or more and is mixed by formula proportion by version in 2010.In GMP10000 level toilet, with above-mentioned mixed raw materials medicine adopt the fully-automatic capsule filling machine respectively fill become hard capsule and soft capsule.Also can process the above-mentioned end product of other type by the related preparations standard criterion.The end product of processing 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 processes the raw materials of effective components composition---2 parts of Actinolitum, 3 parts of Fructus Evodiaes, 1 part of Radix Rehmanniae Preparata, 3 parts of Radix Achyranthis Bidentataes, 3 parts of universe Rhizoma Zingiberis Recens, 3 parts of the Rhizoma Atractylodis Macrocephalaes.

Its manufacture process is following: in GMP10000 level toilet with extractum, nanoparticle, microcapsule, nanoparticle in 4: 2: 2: after 2 ratios are mixed; Adopt a version " preparation part of Chinese pharmacopoeia hard capsule standard in 2010; Do not add adjuvant, antiseptic; Adopt fully-automatic capsule filling machine fill hard capsule, process hard capsule.Carry out several again, bottle, seal, paste labeling, play exterior and interior packings such as sign indicating number, vanning.Unify instantaneously sterilising by production batch at last, and open the sterilization report.

" embodiment two "

Press the following crude drug of preceding method preparation: water drug-decocting concentrating liquid, nanometer liposome, nano-emulsion, microemulsion.

It processes the raw materials of effective components composition---2 parts of Actinolitum, 3 parts of Fructus Evodiaes, 1 part of Radix Rehmanniae Preparata, 3 parts of Radix Achyranthis Bidentataes, 3 parts of universe Rhizoma Zingiberis Recens, 3 parts of the Rhizoma Atractylodis Macrocephalaes.

Its manufacture process is following: in GMP10000 level toilet with water drug-decocting concentrating liquid, nanometer liposome, nano-emulsion, microemulsion in 4: 2: 2: after 2 ratios are mixed; Adopt a version " preparation part of Chinese pharmacopoeia soft capsule standard in 2010; Do not add adjuvant, antiseptic; Adopt full-automatic soft capsule filling machine packing soft capsule, process soft capsule.Carry out several again, bottle, seal, paste labeling, play exterior and interior packings such as sign indicating number, vanning.Unify instantaneously sterilising by production batch at last, and open the sterilization report.

" embodiment three "

Press the following crude drug of preceding method preparation: extractum, nanoparticle, nano-emulsion.

It processes the raw materials of effective components composition---2 parts of Actinolitum, 3 parts of Fructus Evodiaes, 1 part of Radix Rehmanniae Preparata, 3 parts of Radix Achyranthis Bidentataes, 3 parts of universe Rhizoma Zingiberis Recens, 3 parts of the Rhizoma Atractylodis Macrocephalaes.

Its manufacture process is following: after in the GMP10000 level toilet extractum, nanoparticle, nano-emulsion being mixed in 4: 3: 3 ratios, " a preparation part of Chinese pharmacopoeia membrane standard, filmogen adopts polyvinyl alcohol, processes membrane to adopt version in 2010.Adorn box again, seal, paste labeling, play exterior and interior packings such as sign indicating number, vanning.Unify instantaneously sterilising by production batch at last, and open the sterilization report.Every membrane area size is the 2-40 square centimeter, and every medicine film pasted 12-72 hour, pasted the medicine position: positions such as neck, chest, back part, abdominal part, shank, foot bottom, Ashi point.

Can find out through above-mentioned text description: novelty and breakthrough that the present invention has essence are to have found out the key point that Actinolitum circle Chinese medicine compound Chinese and western medicine theory combines, and the compound compatibility of modern Chinese medicine and technology of preparing can change the pharmacokinetic parameter of medicine monomer, effective ingredient or effective part group.This has proved the scientific meaning of Chinese medicine compound compatibility from the pharmacokinetics level." very just being harmonious; negative and positive intercommunication, coordinating water and fire, precise and tiny circle melt; greatness lies in the capacity " is the elite in the classical works such as Chinese Zhou Yi, Taoism, Huang di's Canon of Medicine, is simple philosophy doctrine thought, also is the research and development thinking and the basic guiding theory of the integrated novel form of this medicine.The traditional Chinese medical science always just has the doctor to be prone to saying of homology, skill of a doctor homology.This precise and tiny circle of the present invention just melts integration theoretical basis.Among the present invention: monomer, effective site, nanoparticle and carrier etc. be strange, be tiny, be cloudy.Traditional Chinese medical science organic conception, Chinese medical concrete, water drug-decocting concentrating liquid etc. be just, be grand, be the sun.Very just be harmonious then negative and positive intercommunication, the negative and positive intercommunication is then coordinating water and fire, is the optimum balance attitude.Doctor trained in Western medicine research is precise and tiny, and theory of Chinese medical science is that circle melts, and both very just are harmonious, and have just really embodied the organic conception of the combination of Chinese and Western medicine, and " close " is that " integration " is for holding.The tidemark that greatness lies in the capacity, the coordinating water and fire the present invention of being only asked most.This integrated novel form is through the reasonable compatibility of Chinese medicine monomer, effective site, active substance, Chinese medicine active substance crowd, 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 through skin.

See that further the various Chinese medicine particle diameter major parts that the present invention prepares are the granule of 50～1000 nanometers.Adopt different nano-medicament carriers and technology can be prepared into nanoparticle, nanosphere, solid ester plastid, nano-emulsion, pharmacosomes, microgranule, millimicro ball, little assist etc.Its particle size distribution is between 10 microns of 10 nanometers----.Theoretical according to difference, the difference of slow controlled release time and the traditional Chinese medical science monarch of medicine pharmacology, targeting then, reasonable compatibility mixes, and can be respectively charged among hard capsule and the soft capsule.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 property, 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, and modern Chinese medicine prepares and production has proposed a practical effective novel form compatibility program for Actinolitum is justified.Be to have substantial innovation and technological break-through.

Claims (10)

1. Actinolitum rounding mould assembly novel form technology of preparing and production method thereof is characterized in that: 2 parts of this novel form raw materials of effective components and weight proportion---Actinolitum, 3 parts of Fructus Evodiaes, 1 part of Radix Rehmanniae Preparata, 3 parts of Radix Achyranthis Bidentataes, 3 parts of universe Rhizoma Zingiberis Recens, 3 parts of the Rhizoma Atractylodis Macrocephalaes.

Wherein, said each Chinese medicine is rich in one or more trace element such as organic zinc, selenium.

2. a kind of Actinolitum rounding mould assembly novel form technology of preparing according to claim 1 and production method thereof; It is characterized in that: medicine is become medicine support material medicine with preparing carriers; Crude drug can be one or more combinations in nanoparticle, nanoparticle, micron liposome, nanometer liposome, solid lipid nanoparticle, nanometer polymer micelle, pharmacosomes, nano-emulsion, lipid microsphere, microcapsule, microemulsion, lipid liquid, nanometer film, nanometer suspension liquid, the microcapsule etc., and can as required one or more be mixed.The described protection domain of this claim is not only the said medicine support material medicine in the said scope, is also included within to prepare on its basis or add the curative effect that other do not influence its disease of controlling, and just makes the pharmaceutical carrier crude drug of its better efficacy.

3. according to claim 1,2 described a kind of Actinolitum rounding mould assembly novel form technology of preparing and production methods thereof; It is characterized in that: the drug carrier material that this novel form is selected for use, activating agent, help excipient substances such as Emulsion, dispersant be gelatin, albumin, starch and derivant thereof, alginate, beta-schardinger dextrin-, protein, chitosan and derivant thereof, lactose, hydroxypropyl emthylcellulose, ethyl cellulose, cellulose acetate phthalate, metering system acetate, polylactic acid, cyanoacrylate, semisolid poe, triglyceride (as in three stearic acid, three Palmic acids, three lauric acids, three oleic acid etc., the glyceride of LCFA), in glyceride (, containing the synthetic glyceride of list, two, triglyceride), cholesterol, Polyethylene Glycol, microcrystalline wax, whale ester type waxes, erythrocyte, Montmorillonitum, tea powder etc. one or more like glyceryl monostearate.The described protection domain of this claim is not only the said medicine adjuvant in the said 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 described a kind of Actinolitum rounding mould assembly novel form technology of preparing and production methods thereof; It is characterized in that: said integrated novel form adopts medicament nano powder body, micro-powder, medicine monomer, effective ingredient, effective site, active substance crowd, Chinese medical concrete, water drug-decocting concentrating liquid and different drug adjuvant, pharmaceutical carrier to unite use according to indexs such as the pharmacology of traditional Chinese medical science global theory, compatibility theory and medicine, drug effect, medicine generation, toxicitys.And can mix its one or more according to the preparation needs.

5. according to claim 1 or 2 or 3 or 4 any described a kind of Actinolitum rounding mould assembly novel form technology of preparing and production methods thereof, it is characterized in that: the integrated novel form end product that finally can form is: tablet, powder, suppository, stick, granule, soft capsule, hard capsule, effervescent, drop pill, aerosol, unguentum, oral solution, slow releasing tablet, controlled release tablet.

6. Actinolitum rounding mould assembly novel form technology of preparing 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 powder and micron, subsequent use.

Step 2: get 30%--90% alcohol-water solution mixed soaking 1-2 days that 60% Actinolitum, Fructus Evodiae, Radix Rehmanniae Preparata powder and micron doubly measure with 6-12; Reflux, extract, 3 times; Extract water solublity, pure dissolubility, three kinds of active drug compositions of ester dissolubility simultaneously, recovered alcohol gets extract with subsequent use.

Step 3: get 60% Radix Achyranthis Bidentatae, universe Rhizoma Zingiberis Recens, Rhizoma Atractylodis Macrocephalae powder and micron; Adopt the ultrasonic dispersing extraction equipment of independent research to disperse respectively to extract; Ultrasonic power is: 800W-3000W, supersonic frequency: 28KHz--120KHz, extraction time are 10-100 minute, get extract with subsequent use.

Step 4: with step 2, step 3 gained Chinese medicine extract, adopt the nanon ball-mill of independent research to grind 4-16 hour, get particle size distribution and be the nano powder of 50-1000 nanometer, subsequent use.

Step 5: get each Chinese medicine powder and micron of 40%, boiled 3 times with the traditional Chinese medicine extracting machine decocting after being soaked in water two hours, decocting liquid merges and filters, and filtrating concentrates, extractum or water drug-decocting concentrating liquid with subsequent use.

Step 6: with step 2, step 3, step 4 gained Chinese medicine extract, nano powder as required with and the different property of medicine, pharmacological actions; Can adopt technology such as leafing, macroporous absorption, gel molecular screening, mould separation, ultracentrifugation to prepare respectively, obtain medicine materials such as different drug monomer, effective site, active substance crowd.

Step 7: above-mentioned gained medicine material is adopted different drug adjuvant and carrier, and " related preparations part of standards standard was with " requirement of version Chinese pharmacopoeia appendix XIXE " microcapsule; microsphere; with the Liposomal formulation guideline " in 2005 in waiting adopts the high pressure breast to spare method respectively in the Chinese pharmacopoeia by version in 2010; Inclusion technique; Solid state technology; Polishing; Solvent-fusion method; Squeezing and pressing method; Complex coacervation; Emulsion-crosslinking method; The polymerization dispersion method; Fusion method; Technology such as freeze-drying are prepared into nanoparticle; Nanoparticle; The micron liposome; Nanometer liposome; Solid lipid nanoparticle; Nanometer polymer micelle; Pharmacosomes; Nano-emulsion; Lipid microsphere; Microcapsule; Microemulsion; Lipid liquid; Nanometer film; Nanometer suspension liquid; Crude drug such as microcapsule.The crude drug particle diameter is between 10 nanometers-10 micron.

Step 8: " preparation part of standards code requirement in the Chinese pharmacopoeia was got in the crude drug such as step 5 gained Chinese medical concrete or water drug-decocting concentrating liquid and step 7 gained nanoparticle, liposome, nano-emulsion, microcapsule one or more and is mixed by formula proportion by version in 2010.

Step 9: in GMP10000 level toilet, with above-mentioned mixed raw materials medicine adopt the fully-automatic capsule filling machine respectively fill become hard capsule and soft capsule.Also can by version in 2010 " Chinese pharmacopoeia related preparations standard criterion is processed the above-mentioned end product of other type.

Step 10: the end product of processing 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. a kind of Actinolitum rounding mould assembly novel form technology of preparing according to claim 6 and production method thereof; It is characterized in that: pulverizing of using in said step 1, step 2, the step 3 and method for distilling; 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, breaking method, method for distilling and the technology of more advanced, more environmental protection.

8. a kind of Actinolitum rounding mould assembly novel form technology of preparing according to claim 7 and production method thereof; It is characterized in that: crude drug such as the dissimilar nanoparticle that employing different pharmaceutical adjuvant is prepared in the medicine monomer in the said step 6, active substance, effective site technology of preparing and the said step 7, nano-emulsion; The described protection domain of this claim is not only described technology of preparing and method; As required, be also included within add on its basis or use other better effects if, more economical, upgrade, the method for preparing and the technology of more advanced, more environmental protection.

9. a kind of Actinolitum rounding mould assembly novel form technology of preparing according to claim 8 and production method thereof; It is characterized in that: its key point 1 is different utilization nano-carrier GC-MSs different according to the particle diameter of crude drug and the property of medicine, can produce the gentle controlled capability of different targeting property.

10. a kind of Actinolitum rounding mould assembly novel form technology of preparing according to claim 9 and production method thereof is characterized in that: its key point 2 is to develop simultaneously by interior external administration, can take four time periods respectively by midnight-noon and ebb-flow doctrine, energy and blood of human body flowing law.Also can be prepared into membrane, transdermal agent is attached to the human body different parts respectively by the energy and blood of human body flowing law, can directly absorb through skin.