CN102526322A - Preparation technology and production method of novel integrated Jiaoai decoction dosage form - Google Patents

Abstract

The invention relates to a preparation technology and production method of a novel integrated Jiaoai decoction dosage form. The novel integrated dosage form comprises the following raw mateirals containing active ingredients in parts by weight: 2 parts of donkey-hide gelatin, 2 parts of Ligusticum wallichii, 2 parts of baked licorice, 3 parts of angelica, 3 parts of Folium Artemisiae argyi, 4 parts of white paeony root and 4 parts of prepared rehmannia root. The production process comprises the following steps: supersonic jet milling, alcohol-water extraction, ultrasonic milling and extraction, decoction in water and concentration, supersonic spray drying, nanoscale grinding, high-pressure homogenization, nanoparticle preparation and the like. According to the invention, the advantages of multiple collaboration, multiple targets and the like embodied by utilizing the nano carrier combined technology are emphasized; after large scale production, the production cost can be substantially lowered, the product quality can be remarkably improved and the targeting and slow/controlled release property of the medicines is enhanced; the dosage form can be simultaneously administrated internally and externally and can be taken in four time periods respectively according to the midnight-noon ebb-flow and the human blood flow rule; and the dosage form can be prepared into film agents and transdermal agents which can be respectively stuck to different parts of human bodies according to the midnight-noon ebb-flow and the human blood flow rule and can be directly absorbed by skin.

Description

Integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction and production method thereof

Technical field

The present invention relates to the integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction, the invention still further relates to integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction 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.

Ass-hide Glue and Argyi Leaf Decoction comes from " Song's formulary of peaceful benevolent dispensary ".The side is by Colla Corii Asini (broken, fry dry), Rhizoma Chuanxiong, Radix Glycyrrhizae (processing), each two liang; Radix Angelicae Sinensis, Folium Artemisiae Argyi (little stir-fry), each three liang; Radix Paeoniae Alba, ripe universe Radix Rehmanniae, each four liang of composition.Function cures mainly: control the impairment caused by overstrain vim and vigour, dash to appoint deficiently, menorrhagia drenches drop and leaks down, and is continuous day after day, umbilicus abdomen pain, and gestation will take the photograph inappropriate, frequent fetal movement, abdominal pain with tenesmus.Or the impairment caused by overstrain collaterals of the uterus, abdominal pain during pregnancy leaks blood, the vexed unrest of lumbago, or, rob the heart on the tire because of decreasing, and run quickly to dash and lose heart, and, dash and appoint the deficiency of vital energy because of galactopoiesis, can not keep within bounds, continuous through the stranguria with blood drop, prolong and draw life, gradually become to win thin.

The pharmacological action of Colla Corii Asini:

The refined soln of Colla Corii Asini can be made plasma expander, makes the cat increased blood pressure of traumatic shock, and the generation of erythrocyte, haemachrome is had facilitation.40% Colla Corii Asini solution 15ml/kg irritates stomach, and the rabbit injury of lung that oleic acid is caused has protective effect, and the lung microcirculation improves, and the lung coefficient is less than matched group, no edema, and the lung pathology variation is light than matched group; Can improve the boiling hot back of rabbit ear vascular permeability and increase, expansion rabbit bulbar conjunctiva blood capillary makes blood flow little slow, and haematocrit and whole blood contrast viscosity are all descended, and erythrocyte electrophoretic time shortens.Colla Corii Asini aqueous solution 2.5g/kg or 5.0g/kg irritated stomach 7 days, and mice can obviously be improved rosette and formed percentage rate, and the spleen atrophy due to the antagonism hydrocortisone shows that the pair cell immunologic function has facilitation; Simultaneously can improve carbon clearance speed, enhanced natural killer cell (NK) activity, showing has the promotion non-specific immunity.Colla Corii Asini 18g/ day is added in the feedstuff feeds, and experimental nephritis rabbit is had improvement, obtain positive nitrogen balance, and matched group still is a negative nitrogen balance.

The pharmacological action of Rhizoma Chuanxiong:

The Rhizoma Chuanxiong decoct is to Bufo siccus and the frog heart of exsomatizing, and when concentration is 10-5～10-4, makes contractive amplitude increase, heart rate slow slightly.Ligustrazine is dirty and dabbling guinea-pig heart is dirty before anoxia or during anoxia that the effect of the myocardium shrinkage function of inhibition arranged to guinea-pig heart.Ligustrazine has the significant protection effect to myocardial ischemia reperfusion injury, and it is active to increase blood SOD, suppresses LDH and MDA content and rises.Rhizoma Chuanxiong and extract thereof all have effects such as coronary artery dilating, increase coronary flow, reduction myocardium keto consumption.Rhizoma Chuanxiong can significantly increase the Medulla Leporis seu Oryctolagi blood flow, and its effect is superior to papaverine and low molecular dextran.Ligustrazine can make the anesthetized dog cerebral blood flow significantly increase, and vascular resistance descends.The mechanism of action of Rhizoma Chuanxiong control cerebral ischemia, with dynorphin A1-13 appearance immunologic active material in raising blood plasma and the marrowbrain, activation of platelet in the body when suppressing cerebral ischemia, the TXA2-PGI2 dysequilibrium is relevant in the correction circulation.Rhizoma Chuanxiong can improve pia mater encephali microcirculation and fluidised form, increases cerebrovascular pulsation blood volume.Rhizoma Chuanxiong, Rhizoma Chuanxiong total alkaloids and ligustrazine descend the anesthetized dog vascular resistance, and brain, femoral artery and lower extremity blood flow are increased.Rhizoma Chuanxiong alkaloid, phenol property part and ligustrazine can suppress potassium chloride and the contraction of epinephrine to the stripped thoracic aorta bar of rabbit.Rhizoma Chuanxiong extractum, infusion, ethanol infusion, alcohol leaching liquid and alkaloid are to anesthesia actions such as dog, cat, rabbits, no matter intramuscular injection or intravenous injection all have remarkable and persistent hypotensive effect.Ligustrazine has the strong inhibition effect external to ADP, collagen, thrombin, the inductive rabbit platelet aggregation of arachidonic acid.Accumulative platelet is had depolymerisation, and can reduce ADP induced platelet electrophoresis is slowed down rate and PAR, its effect is identical with aspirin and persantin.Ligustrazine is through cAMP content (concentration) anticoagulant in platelet increasing or the blood plasma.Can the film load be increased, thereby platelet aggregation is suppressed through the ca2+ on its platelet membrane of displacement again.Ligustrazine has erythrocyte and platelet surface electric charge, the blood viscosity lowering of raising, improves the hemorheological property effect.The stripped gravid uterus test of rabbit shows that Rhizoma Chuanxiong extractum strengthens uterine contraction, becomes contracture eventually; Anaesthetize in the anti-uterus that makes of heavy dose, and contraction stops.Rhizoma Chuanxiong effective ingredient cyclobutenyl mouth lactone and butyl alkene lactone have very strong inhibition uterine contraction effect, and the animal tracheal smooth muscle is had significant relexation.Ferulic acid and neutral compound also have spasmolysis.Ligustrazine can make protein decreased every day of rabbit Masugi nephritis, has certain effect to alleviating glomerule pathological changes, the formation of inhibition crescent and glomerule fibrosis.Rhizoma Chuanxiong, ligustrazine, ferulic acid and volatile oil are used the rabbit renal failure that can alleviate due to the glycerol in advance.

Ligustrazine causes the smooth muscle spasms such as isolated helical strips of guinea, pulmonary artery bar and irritated lung tissue of breathing heavily due to the medium to leukotriene C, D4, histamine, prostaglandin F2 2, indometacin etc. all has certain inhibitory action.Rhizoma Chuanxiong has obvious sedation.Movable inhibited to animal brain when Rhizoma Chuanxiong volatile oil is a small amount of has excitation to medulla oblongata respiratory center, vasomotor center and spinal reflex maincenter.The Rhizoma Chuanxiong decoct has certain curative effect to animal radiation sickness experimental therapy.Its water solublity crude preparation by using all has protective effect to radio exposure and the chlormethine damage of rat, mice and dog.Ligustrazine alleviates radiation fibrosis of lung for reducing radioactive proliferation of fibrous tissue, the radioactive skin fibrosis, and radioactivity intestinal adhesion all has effect.Chuanxiong rhizome oral can promote the to fracture union of fracture of rat and rabbit and the absorption of hematoma.Rhizoma Chuanxiong has the effect of vitamin antagonist E deficiency disease.Ligustrazine can increase the renal blood flow of anesthetized rabbit, and can diuresis.It is synthetic that ligustrazine can suppress DNA.The in vitro tests Rhizoma Chuanxiong has obvious inhibitory action to large intestine, dysentery, distortion, green pus, typhoid fever, Salmonella paratyphi and vibrio cholera etc.Some pathogenic dermatophytes also there is inhibitory action.Sodium ferulate has anti peroxidation of lipid and reduces complement hemolysis, suppresses complement 3b (c) and the bonded effect of erythrocyte membrane.

The pharmacological action of Radix Glycyrrhizae:

Remove that flavonoid glycosides has obvious protective effect to the rat experiment ulcer in extractum and the Radix Glycyrrhizae of glycyrrhizin.

Radix Glycyrrhizae extractum, glycyrrhizin and enoxolone all have promotion sodium to healthy subjects and animal, the effect of water retention; Low dose of glycyrrhizin (every 100ug) can make rat chest gland atrophy and adrenal gland's weight increase, and produces the effect of glucocorticoid cortisone appearance.Then the effect of glucocorticoid appearance is not obvious when heavy dose of, only presents the effect of mineralocorticoid appearance.Radix Glycyrrhizae extractum and glycyrrhizin all have certain detoxification ability to some drugs poisoning, alimentary toxicosis, interior metabolism product poisoning.The effective ingredient of Detoxication is a glycyrrhizin; Detoxification machine is made as glycyrrhizin has adsorption to poisonous substance; Glycyrrhizin hydrolyzate glucuronic acid can combine with poisonous substance; And GLYCYRRHIN have the effect of adrenocortical hormone appearance, the result of the aspect combined factors effects such as detoxification ability of enhancing liver.Enoxolone has tangible central antitussive effect, and heavy dose of enoxolone can make mouse breathing suppress.Glycyrrhizin, glycyrrhetate still have anti-inflammatory and antiallergic, anti-liver injury, anti-promoting, antibiotic, anti AIDS virus (glycyrrhizin) effect in addition.

The pharmacological action of Radix Angelicae Sinensis:

The Radix Angelicae Sinensis nature and flavor are sweet, hot, temperature.Return liver, the heart, spleen channel.Function with cure mainly: enrich blood and invigorate blood circulation, menstruction regulating and pain relieving, loosening bowel to relieve constipation.Be used for blood deficiency and yellow complexion, dizzy cardiopalmus, menoxenia, amenorrhea dysmenorrhea, asthenia cold abdominalgia, dryness of the intestine constipation, rheumatic arthralgia, injury from falling down, ulcer sores.The Radix Angelicae Sinensis (processed with wine) promoting blood circulation to restore menstrual flow.Be used for the amenorrhea dysmenorrhea, rheumatic arthralgia, injury from falling down.The pharmacological action of Radix Angelicae Sinensis: Radix Angelicae Sinensis and sodium ferulate thereof have tangible anti thrombotic action.Rat experiment shows that Radix Angelicae Sinensis can make the thrombosis dry weight significantly reduce, and the thrombosis growth rate descends than matched group, thrombosis contraction in length, plasma prothrombin time and KPTT significant prolongation.Radix Angelicae Sinensis is the traditional Chinese medical science key medicine of " enriching blood, invigorate blood circulation ", clinically shows better curative effect with experimentation. and the Radix Angelicae Sinensis infusion gives that mice is oral significantly to promote hemoglobin and erythrocytic generation. and its anti-anemia effect maybe be relevant with compositions such as contained vitamin B12, nicotinic acid, folinic acid and biotin, folic acid.Ferulic acid has the effect that suppresses the liver synthetic cholesterol. and the antioxidation of Radix Angelicae Sinensis and composition ferulic acid thereof and free radical scavenging effect are concerning blood vessel wall; Has the injury-free effect of protection inner membrance; Make lipid in the entering of arterial wall with shift out and keep normal dynamic equilibrium, also be unfavorable for platelet adhesion and be gathered on the blood vessel wall; Its cholesterol reducing effect can suppress lipidosis in blood vessel wall; Its antiplatelet function can stop mural thrombus to form again, and three kinds of pharmacological actions of this of Radix Angelicae Sinensis and composition ferulic acid thereof are coordinated mutually, are expected to produce antiatherogenic effect.

Radix Angelicae Sinensis has very significant activation external to people's blood superoxide dismutase (SOD).The whole bag of tricks proof ferulic acid is a kind of antioxidant.Radix Angelicae Sinensis has effect for reducing blood fat to hyperlipemia, and its effect is similar with medicines such as clofibrates.To in animal and human's isolated cells 2, the 3-diphosphonic acid generates that facilitation is arranged, and reduces the affinity of hemoglobin and oxygen, promote to be with oxygen hemoglobin release oxygen in tissue, thereby increased the function of erythrocyte transports oxygen.Radix Angelicae Sinensis pours into the cerebral tissue MDA after to cerebral anoxia, ischemia again and increases the obvious suppression effect is arranged.Contained ferulic acid has direct minimizing H2O2 content, and combines with membrane phospholipid acyl ethanolamine, through direct elimination free radical, and the infringement of antagonism radical pair tissues such as inhibited oxidation reaction and radical reaction.

Radix Angelicae Sinensis early has report to central nervous system's inhibitory action.The Japan scholar reports that Japanese Taihe county Radix Angelicae Sinensis volatile oil has effects such as calmness, hypnosis, analgesia, anesthesia.Ligustilide has inhibitory action widely to the central nervous system, and has and the tranquilizer similar action, and no obvious syngignoscism own only plays the effect of strengthening hypnotic.Therefore, tentatively think Radix Angelicae Sinensis to the inhibitory action of nervus centralis, possible ligustilide is the main component that pharmacologically active occurs, and its effect relates to the cerebral limbic system probably, but actually why its mechanism of action, remains further research.

Radix Angelicae Sinensis all has antibacterial action to external dysentery, typhoid fever, paratyphoid fever, escherichia coli, diphtheria corynebacterium, vibrio cholera and a, B Hemolytic streptococcus etc.These article of Po can reduce the mice capillary permeability.External can be quickened rabbit ear wound healing, and contrafluxion, leukocyte and fiber are soaked into, and newborn epithelium regeneration has hemostasis and strengthens the tip Circulation local organization.Explain that Radix Angelicae Sinensis has antibiotic, antiinflammation.The clinical diseases such as suppurative maxillary sinusitis, acute nephritis, bone phlebitis, scleroderma and psoriasis that can be used for.The Radix Angelicae Sinensis hot water extract has the obvious suppression effect when its adjuvant arthritis acute attack to chronic rheumatoid sexually transmitted disease (STD) experimental animal model.

The pharmacological action of Folium Artemisiae Argyi:

Oleum Folium Artemisiae Argyi and Folium Artemisiae Argyi decocting liquid have bacteriostasis preferably.With Folium Artemisiae Argyi ward is carried out the sootiness sterilization, can make airborne total number of bacteria rate of descent reach 73%.Report is arranged, and Folium Artemisiae Argyi and Folium Artemisiae Argyi merge Rhizoma Atractylodis and are used for the ward sterilization, and effect obviously is superior to electronic sterilizer, and the moxa roll sootiness still can reduce the bacterial reproduction of burn wound.Fire victim's wound surface is after the moxa roll sootiness, and wound surface bacterium colony slip 74.64% is treated with moxibustion behind the Cavia porcellus mycobacterium tuberculosis infection; The peritoneal exudate smear for microscopic examination is the result show; Big Monocyte has been swallowed the percentage of cells of antibacterial, and moxibustion group is obviously higher, and average 17.75%.Tuberculosis guinea pig intraperitoneal injection fast knot nuclear bacillus liquid, the peritoneal exudate smear, full-brown macrophage is more in the moxibustion group smear, and phagocytosis is stronger.The Folium Artemisiae Argyi hot water extract has strong ACA composition.Give mouse stomach 3d with Folium Artemisiae Argyi oil with 0.5ml/kg, abdominal cavity inflammatory exudation leukocytes phagocytic rate is obviously increased.Irritate clothes or intramuscular injection or aerosol delivery with Oleum Folium Artemisiae Argyi to Cavia porcellus, the asthma that is caused by histamine or acetylcholine is all had antiasthmatic effect.Oleum Folium Artemisiae Argyi has resistance inhibitor action to the release of sensitized guinea pig lung tissue and tracheal smooth muscle slow reacting substance (SRS-A).Oleum Folium Artemisiae Argyi spraying sucks, irritates stomach or intramuscular injection and Cavia porcellus sucked the panting property tic that acetylcholine and histamine cause obvious antiasthmatic effect is arranged.The 4-terpinenol that from Folium Artemisiae Argyi, proposes is irritated stomach also has remarkable antiasthmatic effect.Alpha-terpineol is irritated clothes and Cavia porcellus is sucked the asthma that acetylcholine and histamine bring out protective effect is promptly arranged, and trans carveol also is the effective ingredient of relievining asthma.Oleum Folium Artemisiae Argyi has slight relexation to guinea-pig isolated trachea; The bronchoconstriction that Oleum Folium Artemisiae Argyi Emulsion can obviously cause antihistamine.

The hot water extract of Folium Artemisiae Argyi (polysaccharide) adds in people's the serum, the SC value is descended, and prove that this is the complement activation result.Shan Tianshi finds to have intensive ACA among the living Folium Artemisiae Argyi hot water extract, and active main component is an acidic polysaccharose.Oleum Folium Artemisiae Argyi is irritated stomach has obvious antitussive effect to the guinea pig cough that the acrylic aldehyde citric acid causes, and volatile oil component 4-terpinenol is irritated stomach also has tangible antitussive effect.Oleum Folium Artemisiae Argyi has inhibitory action to the contractility of the Bufo siccus heart that exsomatizes, extrasomatic rabbit heart, the contraction that Oleum Folium Artemisiae Argyi can cause antiadrenergic drug and histamine.Can strengthen anastalsis behind the Folium Artemisiae Argyi system carbon, Folium Artemisiae Argyi Blood clotting after hot-working is handled can significantly strengthen.Oleum Folium Artemisiae Argyi suspension (every 1ml contains Oleum Folium Artemisiae Argyi 75u1) 8ml/kg makes the normal rat bile flow increase by 91.5% through the duodenum drug administration by injection; 3ml/kg increases by 89%, and the carbon tetrachloride poisoning rat is also had choleretic effect, but; Mice also there is choleretic effect.The Folium Artemisiae Argyi decoct is excitation to unpregnancy rabbit isolated uterine, makes to shrink to strengthen, and can cause the contraction of tetanic property, keeps more than the 1h.Experiment proof Folium Artemisiae Argyi has effects such as anti-alimentary tract tumor, breast carcinoma.In addition, the moxa-moxibustion of pharmacological evaluation proof has effects such as enhance immunity, antitumor, shock, hepatoprotective, control cerebrovascular disease, but also antiulcer, digestion promoting, analgesia, analgesic etc.; Pharmacological evaluation has also disclosed sick mechanism such as moxibustion treatment epidemic hemorrhagic fever, diabetes, schizophrenia, adrenal cortex atrophy.

The pharmacological action of the Radix Paeoniae Alba:

Radix Paeoniae Alba bitter in the mouth, acid, cold nature.Go into liver, spleen channel.Function: nourishing blood to suppress the hyperactive liver, slow middle pain relieving, astringing YIN to stop sweating.Cure mainly: the breast abdomen pain over the hypochondriac region, limb pain twin, dysentery stomachache, headache, dizzy, spontaneous sweating, fever due to yin deficiency, menoxenia, metrorrhagia, leukorrhagia.Radix Paeoniae Alba pharmacological action:

The writhing response that the paeoniflorin Dichlorodiphenyl Acetate causes has significant analgesia role, share with the methanol complex of Radix Glycyrrhizae, and the two Dichlorodiphenyl Acetate writhing response has the synergic antalgic effect.White peony root's total glycoside (TGP) suppresses the mouse writhing reaction to morphine, clonidine has synergism.The analgesic activity of white peony root's total glycoside can not be blocked by Allylnoroxymorphone, and the GPI longitudinal muscle that also not influencing LCF stimulates shrinks.The analgesic activity of the prompting Radix Paeoniae Alba is not due to the excited opiate receptor.The white peony root's total glycoside site of action is at high-level center.White peony root's total glycoside can obviously suppress the mice activity; The mice mobbing reaction that electricity irritation is caused also has obvious inhibitory action.The Radix Paeoniae Alba hydrotrope can obviously prolong the time-to-live of myocardial ischemia due to the isoproterenol; Antagonism is changed by the electrocardiogram that pituitrin causes; Increase the nutrient flow amount of mouse cardiac muscle.Show in the body experiment: the Radix Paeoniae Alba has vasoconstrictive and the effect that increases Peripheral resistance, and white peony root's total glycoside can make the rabbit diastolic pressure raise, and dp/dtmax increases; Decreased heart rate; Phentolamine strengthens the NA boosting in addition to its no blocking-up effect of boosting, and strengthens the effect of intensity of heart sounds.

Paeoniflorin has spasmolysis preferably, and its spasmolysis is the result that it directly acts on the intestinal tube smooth muscle.The leachate of paeoniflorin and Radix Paeoniae all has the spontaneous contraction of inhibition to the guinea pig in vitro small intestinal, the effect of reduction tonicity, and the intestinal tube that acetylcholine is caused shrinks obviously effect of nothing, but can suppress the intestinal tube contraction that barium chloride causes.It is relevant with adenosine appearance material that the effect of the Radix Paeoniae Alba is considered to, but theophylline can not suppress the effect of Radix Paeoniae fully, so the effect of Radix Paeoniae still has other materials to participate in except outside the Pass having with adenosine appearance material.The glycocide of Radix Paeoniae is excitation to the motion of mice isolated uterine during low concentration, then be inhibitory action during high concentration.The uterine contraction that paeoniflorin causes oxytocin has the obvious suppression effect.

Radix Paeoniae Alba extract raises to hepatic injury due to the D-galactosamine and SGPT has tangible antagonism, SGPT is reduced, and make hepatocellular pathological changes recover normal with downright bad.The lactic acid dehydrogenase that the rat acute hepatic injury that the ethanol extraction of the Radix Paeoniae Alba can make aflatoxin B1 cause is showed and the gross activity of isozyme raise and are minimized.White peony root's total glycoside possibly have protective effect to hepatocyte injury, therefore the transaminase is reduced.White peony root's total glycoside has antiinflammatory and function dependency ground immunoregulation effect to adjuvant arthritis rats.Radix Paeoniae Alba extract can significantly suppress the impatient property of rat Ovum Gallus domesticus album inflammation edema, and granuloma induced by implantation of cotton pellets is also had its outgrowth effect of inhibition.

Research shows: the Radix Paeoniae Alba has potentiation to the phagocytic function of macrophage.White peony root's total glycoside has regulating action to phagocytosis of macrophages; White peony root's total glycoside produces interleukin-1 to lipopolysaccharide-induced rat abdominal cavity macrophage and has the effect that low concentration promotes and high concentration suppresses; Because interleukin-1 all plays an important role in the formation of immunomodulating and chronic inflammation disease; Therefore can think that the generation that white peony root's total glycoside is regulated interleukin-1 possibly be its performance immunomodulating and prevent and treat one of arthritic mechanism.The immunity of Radix Paeoniae Alba pair cell also has certain influence.White peony root's total glycoside not only can promote specificity T to regulate inducing of cell in vivo with external, also can increase non-specific T and regulate inducing of cell.White peony root's total glycoside induces different T to regulate cell has tangible function and concentration dependent characteristic, and this possibly be the basis of its performance immunoregulation effect.Research shows: the Radix Paeoniae Alba still can influence humoral immunization.The Radix Paeoniae Alba can promote the generation of splenocyte antibody, strengthens mice specifically to the erythrocytic humoral response property of immunity.There is report to think that Radix Paeoniae Alba hydrotrope lumbar injection can obviously prolong the normobaric hypoxia time-to-live of mice.White peony root's total glycoside maybe be through cooling effect and is directly improved the hypoxia-bearing capability that the Cellular respiration function improves mice, and its main site of action maybe be receptor related with H1-the central nervous system.

Zoopery proves: the Radix Paeoniae Alba has preventive effect to rat stress ulcer; Rat at the ligation pylorus; The two is suppressing aspect the gastric secretion synergism is arranged paeoniflorin and Radix Glycyrrhizae methanolic extract, and the gastric acidity secretion is slight rises improving appetite but the extracting solution of Radix Paeoniae root then can make.

Have report to point out, the Radix Paeoniae Alba has that antibacterial action is strong, the characteristics of has a broad antifungal spectrum.Radix Paeoniae Alba decoct has stronger inhibitory action to shigella dysenteriae in vitro, and staphylococcus is also had inhibitory action.Radix Paeoniae Alba tincture can suppress bacillus pyocyaneus.Radix Paeoniae Alba decoct also shows inhibitory action to some pathogenic fungus.Experiment in vitro finds that Radix Paeoniae Alba extract can alleviate the weight in wet base of platelet thrombus, suppresses thrombosis.To the platelet aggregation of ADP and arachidonic acid-induction, antagonism is all arranged, d-cachou extract and progallin A then are the effective ingredient of antithrombotic and platelet aggregation.The Radix Paeoniae Alba extract high concentration has obvious inhibitory action to the pancreas in rat amylase activity; Do not influence enzyme activity when concentration is not more than 16mg/ml, but can make CCK-8 induce tiring of pancreatic acini secreting amylase to reduce by 10 times, but do not influence the secretion that secretin stimulates.Have certain active substance in this selectively acting explanation Radix Paeoniae Alba water soluble ingredient, but the CCK-8 receptor on the antagonism pancreatic acinar cell film.

The pharmacological action of Radix Rehmanniae:

1. blood sugar lowering: live part (R-BP-F) lumbar injection of bosom celebrating Radix Rehmanniae has the blood sugar lowering effect to alloxan induced mice artificial diabetes.

2. hemostasis: the Radix Rehmanniae, Radix Rehmanniae Preparata decoct, fresh rehmannia charcoal, charred RADIX REHMANNIAE are irritated stomach, all can shorten blood coagulation time (capillary tube method) to mice.

3. anti-disseminated inravascular coagulation: Radix Rehmanniae 70% methanolic extract suppresses the rat platelet aggregation that ADP causes, and the antithrombase effect is arranged, and the rat disseminated inravascular coagulation that endotoxin is caused has antagonism.Effects such as anti inflammatory immunity, anti-hepatic injury are still arranged in addition.

Novelty and breakthrough that the present invention has essence are to have found out the key point that Ass-hide Glue and Argyi Leaf Decoction 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 " the integrated novel form of Ass-hide Glue and Argyi Leaf Decoction " 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 integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction and production method thereof are provided.

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

Integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction and production method thereof, wherein: this integrated novel form raw materials of effective components and weight proportion---2 parts in Colla Corii Asini, 2 parts of Rhizoma Chuanxiongs, 2 parts of Radix Glycyrrhizae Preparatas, 3 parts of Radix Angelicae Sinensis, 3 parts of Folium Artemisiae Argyis, 4 parts of the Radix Paeoniae Albas, 4 parts of Radix Rehmanniae Preparata.

Wherein, described each Chinese medicine is rich in one or more trace element such as organic zinc, selenium.Integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf 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 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; Integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf Decoction 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; Integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf Decoction 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; Integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf 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, unguentum, oral solution, slow releasing tablet, controlled release tablet.

Integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf 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 powder and micron, subsequent use.

Step 2: get 30%--90% alcohol-water solution mixed soaking 1-2 days that 60% Colla Corii Asini, Rhizoma Chuanxiong, Radix Glycyrrhizae Preparata, Radix Angelicae Sinensis 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% Folium Artemisiae Argyi, the Radix Paeoniae Alba, Radix Rehmanniae Preparata 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.

Integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf Decoction 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; Integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf Decoction 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; Integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf Decoction 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, integrated novel form technology of preparing of above-mentioned a kind of Ass-hide Glue and Argyi Leaf Decoction 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, 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 the Ass-hide Glue and Argyi Leaf Decoction Chinese and western medicine theory combines; The present invention will in time fill up the blank of researching and developing " the integrated novel form of Ass-hide Glue and Argyi Leaf Decoction " 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

Integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction and production method thereof, its special feature is: processing the raw materials of effective components composition does by weight ratio---2 parts in Colla Corii Asini, 2 parts of Rhizoma Chuanxiongs, 2 parts of Radix Glycyrrhizae Preparatas, 3 parts of Radix Angelicae Sinensis, 3 parts of Folium Artemisiae Argyis, 4 parts of the Radix Paeoniae Albas, 4 parts of Radix Rehmanniae Preparata.

Further; Play the synergy of standing like the legs of a tripod on the integrated new drug formulation compatibility of Ass-hide Glue and Argyi Leaf Decoction of the present invention: 1, prepare nanometer, micro-powder, the bioavailability after strengthening the Ass-hide Glue and Argyi Leaf Decoction 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 Ass-hide Glue and Argyi Leaf Decoction 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 Ass-hide Glue and Argyi Leaf Decoction 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% Colla Corii Asini, Rhizoma Chuanxiong, Radix Glycyrrhizae Preparata, Radix Angelicae Sinensis 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% Folium Artemisiae Argyi, the Radix Paeoniae Alba, Radix Rehmanniae Preparata 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 in Colla Corii Asini, 2 parts of Rhizoma Chuanxiongs, 2 parts of Radix Glycyrrhizae Preparatas, 3 parts of Radix Angelicae Sinensis, 3 parts of Folium Artemisiae Argyis, 4 parts of the Radix Paeoniae Albas, 4 parts of Radix Rehmanniae Preparata.

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 in Colla Corii Asini, 2 parts of Rhizoma Chuanxiongs, 2 parts of Radix Glycyrrhizae Preparatas, 3 parts of Radix Angelicae Sinensis, 3 parts of Folium Artemisiae Argyis, 4 parts of the Radix Paeoniae Albas, 4 parts of Radix Rehmanniae Preparata.

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 in Colla Corii Asini, 2 parts of Rhizoma Chuanxiongs, 2 parts of Radix Glycyrrhizae Preparatas, 3 parts of Radix Angelicae Sinensis, 3 parts of Folium Artemisiae Argyis, 4 parts of the Radix Paeoniae Albas, 4 parts of Radix Rehmanniae Preparata.

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 Ass-hide Glue and Argyi Leaf Decoction 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, for the Ass-hide Glue and Argyi Leaf Decoction modern Chinese medicine prepares and production has proposed a practical effective novel form compatibility program.Be to have substantial innovation and technological break-through.

Claims (10)

1. integrated novel form technology of preparing of Ass-hide Glue and Argyi Leaf Decoction and production method thereof is characterized in that: 2 parts in this novel form raw materials of effective components and weight proportion---Colla Corii Asini, 2 parts of Rhizoma Chuanxiongs, 2 parts of Radix Glycyrrhizae Preparatas, 3 parts of Radix Angelicae Sinensis, 3 parts of Folium Artemisiae Argyis, 4 parts of the Radix Paeoniae Albas, 4 parts of Radix Rehmanniae Preparata.

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

2. integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf 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 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, the integrated novel form technology of preparing of 2 described a kind of Ass-hide Glue and Argyi Leaf 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 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 integrated novel form technology of preparing of described a kind of Ass-hide Glue and Argyi Leaf Decoction 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 integrated novel form technology of preparing of described a kind of Ass-hide Glue and Argyi Leaf Decoction and production methods thereof, it is characterized in that: the integrated novel form end product that finally can form is: tablet, powder, suppository, stick, granule, soft capsule, hard capsule, effervescent, drop pill, aerosol, unguentum, oral solution, slow releasing tablet, controlled release tablet.

6. integrated novel form technology of preparing of Ass-hide Glue and Argyi Leaf 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 powder and micron, subsequent use.

Step 2: get 30%--90% alcohol-water solution mixed soaking 1-2 days that 60% Colla Corii Asini, Rhizoma Chuanxiong, Radix Glycyrrhizae Preparata, Radix Angelicae Sinensis 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% Folium Artemisiae Argyi, the Radix Paeoniae Alba, Radix Rehmanniae Preparata 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. integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction 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. integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction 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. integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction 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. integrated novel form technology of preparing of a kind of Ass-hide Glue and Argyi Leaf Decoction 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, directly absorb through skin.