CN1943771A - The pharmaceutical for treatment of vascular lesion through actions on the NEI network - Google Patents

The pharmaceutical for treatment of vascular lesion through actions on the NEI network Download PDF

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CN1943771A
CN1943771A CNA2005101051800A CN200510105180A CN1943771A CN 1943771 A CN1943771 A CN 1943771A CN A2005101051800 A CNA2005101051800 A CN A2005101051800A CN 200510105180 A CN200510105180 A CN 200510105180A CN 1943771 A CN1943771 A CN 1943771A
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rhizoma
collateral
herba
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CN1943771B (en
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吴以岭
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Hebei Yiling Pharmaceutical Research Institute Co Ltd
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Hebei Yiling Pharmaceutical Research Institute Co Ltd
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Abstract

This invention provides drugs which are already known to be able to act effectively on informational molecules of the NET and their acceptors or influence informational molecules and their acceptors' signal transduction pathways, and their applications in preparing medicine for angiopathy treatment. The said drugs include single Chinese herbs, compound Chinese herbs and their preparations, chemical effective constituents, medicinal compounds and their preparations, biologic effective constituents, medicinal compounds and materials for their preparations. It also provides a new kind of drugs which can effectively act on the said mutual informational molecules of the NET and their acceptors, or influence their signal transduction pathways so as to treat angiopathy; and furthermore provides these drugs' preparation methods.

Description

By acting on the medicine of NEI network treatment vascular lesion
Technical field
The present invention relates to the medicine that a class is used for the treatment of vascular lesion; More particularly, relate to that a class can actively act on the total informational molecule (as neurotransmitter, neuropeptide, hormone, cytokine) of nerve-endocrine-immune system network (NEI network) thereby and receptor, maybe can influence the medicine of the signal transduction pathway treatment vascular lesion of total informational molecule and receptor thereof; The preparation method that also further relates to these medicines.
Background technology
Vascular conditions such as cerebrovascular, cardiovascular diseases, peripheral angiopathy and diabetic microvascular complication become the major disease of serious harm human health, and wherein cerebrovascular, cardiovascular diseases are respectively and cause human first and third dead disease.According to " CCEP project implementation status in 2004 and achievement ", annual nearly 2,600,000 people of China die from acute cardio cerebral angiopathy, average people's death every days 7000, per 12 seconds dead 1 people.Thereby urgent need is set up novel drugs, new way and the new method of the vascular lesion control that is with Chinese characteristics, comprises traditional Chinese medicine.
(nerve-endocrine-immunological network Neuro-endocrine-immunityNetwork) is the advanced problems of contemporary medical science and molecular biology research to the NEI network, and its notion is proposed in 1977 by Besedovsky.Each performs its own functions for nerve, endocrine, immune system, coordinates mutually again; Studies confirm that more and more nervous system is by its peripheral nervous synapse widely and excretory neurotransmitter thereof and numerous endocrine hormone even also have the excretory cytokine of neurocyte, is regulating and control functions of immune system jointly; And the various kinds of cell factor that immune system produces by immunocyte and hormonelike material feedback effect are in neuroendocrine system, the biological agents basis that three systems carry out information communication is various neurotransmitteies, neuropeptide, cytokine, hormone etc., its cell surface all has the receptor that receives these informational molecules, simultaneously also can secrete these informational molecules, thereby make three big function systems form the multi-C stereo network structure of human body homeostatic mechanism.The forward position of basic medical research is not only in the research of modern NEI network, at clinical medicine domain great development is arranged also.Progress on Molecular Biology makes us can more in depth understand the gene expression and the regulatory mechanism of various hormones, cytokine etc. and receptor thereof, thus more profoundly between understanding nerve, endocrine, the immune system connecting each other and in morbidity with the important value in treating.It at first is introduced in the etiological study of autoimmune diseasees such as rheumatoid arthritis, systemic lupus erythematosus (sle), and has obtained gratifying achievement.
Simultaneously, nerve, endocrine, each system of immunity role in generation of vascular conditions such as atherosclerosis, acute myocardial infarction, heart failure, hypertension, cerebral infarction, diabetic nephropathy, diabetic peripheral neuropathy, diabetic renal papillary necrosis and evolution process also obtains people's attention day by day.As being example with the atherosclerosis: in recent years, the neuro humor factor that is derived from nervous system inside is subjected to people's attention gradually to the influence that atherosclerosis forms, the main matter basis that the excretory angiotensin of nervous system, neuropeptide tyrosine, vasoactive intestinal peptide, somatostatin and informational molecules such as angiopeptin, calcitonin-gene-related peptide are regulated as neuro humor, can be used as mediator or modified on the one hand, by influencing the neuronic activity of cardiovascular center, realize adjusting to cardiovascular activity; On the other hand, directly or indirectly vasoactive influences the function of blood vessel endothelium and the propagation of smooth muscle cell, and atherosclerotic formation is played an important role.The effect of cytokines such as immune system and excretory interleukin thereof, tumor necrosis factor, interferon in the inflammatory cascade reaction process that atheromatous plaque forms and blood vessel wall takes place also obtained people's common recognition in addition.
Comprehensive documents and materials analysis in recent years, though nerve, endocrine, each subsystem of immunity be existing the argumentation in the mechanism of vascular conditions and control, but also there is not utilization NEI network theory to inquire into the report of research and treatment of vascular pathological changes at present, result through Institute of Medical Information of Chinese Academy of Medical Sciences retrieval CBMdisc (1978-2005) and United States Medicine bibliographic data base (1966-2005) shows, does not retrieve the domestic and foreign literature report of " nerve, endocrine, immunological network and vascular lesion dependency ".
The said channels of Chinese medicine be from do not go out through the pulsation horizontal stroke, segmentation successively, crisscross, spread all over whole body, be distributed widely in the network structure between internal organs, be the activity of earning a bare living and keep human internal environment's stable network system.Channels is divided into the network (gas network) of meridians and the network (blood network) of venation again, and the network operation of meridians is through gas, and the network of venation moves blood, is bringing into play the normal physiological function of " qi warming body, blood nourishing " jointly." through gas " permeates into internal organs skin, extremity bones of the body collectively by gas network face, excite vitality, keep human body substance metabolism and energy metabolism, bring into play warmly supplement nutrition, defend to protect, information is passed on, regulate the effect of control, realize information transmission and orthofunction between internal organs, keep the stable state of body internal and external environment.Gas network and NEI network in the functional status research of the outlook on life of the homeostatic mechanism of multi-C stereo network system, life movement, total system, life movement, to meet aspect the common features such as transformation of biology-psychology-social medicine pattern height similar, disclose gas network and NEI network and have high correlation and inherent concordance.Informational molecule such as neurotransmitter, neuropeptide, hormone, cytokine and receptor thereof are not only the general biological agents basis of NEI network, also should be the Basic of Biology of gas network on molecular level simultaneously.Comprehensive above understanding, the inventor proposes the notion of " gas network-NEI network " thus.
Based on the relevant network ens morbi characteristic of QI and blood, QI and blood can be divided can not be from, qi being the governor of blood, and gas network pathological changes can cause venation systolic and diastolic function and blood operation obstacle.The proposition of " gas network-NEI network " notion, can make people go understanding neural from visual angle widely, endocrine, immunity each system and regulate and control not normal influence to vascular lesion, more in depth inquire into " gas network-NEI network " mechanism of action in the blood vessel pathogenic process, help more profoundly to be familiar with the pathology development law that development takes place vascular lesion, simultaneously also help disclosing the action pathway of medicine in vascular lesion, effect link and action target spot, and under the network ens morbi instructs, can use bimillennium traditional collateral dredging method of treatment and the level of preventing and treating of the collateral dredging medicine major disease that improves this type of serious harm human health.
Summary of the invention
The inventor creatively connects gas network-NEI and vascular lesion and find, can actively act on NEI network total said informational molecule and receptor thereof by using, or the medicine of the signal transduction pathway of said total informational molecule and receptor thereof (comprises single medicinal material, Chinese medicine composition and preparation thereof, the chemistry effective ingredient, Pharmaceutical composition and preparation thereof, biological effective components, Pharmaceutical composition and preparation thereof), just can treat vascular lesion, and screened corresponding medicine in view of the above, be used for the treatment of vascular lesion, such as hypertension, coronary heart disease, diabetes, hyperlipemia and clinically with arteriosclerosis, thrombosis, other disease that microcirculation disturbance etc. are relevant.
Therefore, an object of the present invention is, provide that seven classes of dividing by traditional Chinese medical science network ens morbi are known actively to act on the total informational molecule of NEI network (neurotransmitter for example, neuropeptide, hormone, cytokine) and receptor, and/or the medicine of the signal transduction pathway of total informational molecule and receptor thereof (comprises single medicinal material, Chinese medicine composition and preparation thereof, the chemistry effective ingredient, Pharmaceutical composition and preparation thereof, biological effective components, Pharmaceutical composition and preparation thereof) at preparation treatment vascular lesion, comprise cardiovascular and cerebrovascular disease, hyperlipemia, the diabetes microvascular complication is (as diabetes complicated retinopathy, nephropathy, cardio cerebrovascular affection etc., diabetic foot), application in the medicine of thrombosis etc.
Another object of the present invention is, thereby provides the class can be by positive role in total said informational molecule and the receptor thereof of NEI network or can actively influence the novel drugs (comprising single medicinal material, Chinese medicine composition and preparation thereof, chemical effective ingredient, Pharmaceutical composition and preparation, biological effective components, Pharmaceutical composition and preparation thereof) of the signal transduction pathway treatment vascular lesion of said total informational molecule and receptor thereof;
A further purpose of the present invention is that the preparation method of these medicines is provided.
The informational molecule relevant with the NEI network comprises following a few class at least:
(1) neurotransmitter and hormone: acetylcholine, dopamine, norepinephrine, epinephrine, 5-hydroxy tryptamine, histamine, glutamic acid, Aspartic Acid, γ-An Jidingsuan, glycine, P material and other tachykinin, opioid peptide (beta-endorphin, dynorphin, enkephalin), HRP and neurohypophysis peptide (somatostatin), vasopressin, oxytocin, brain-gut peptide (vasoactive intestinal peptide, gastrin, secretin, cholecystokinin, neurotensin, motilin, glucagon, gastrin releasing peptide etc.), calcitonin-gene-related peptide, neuropeptide tyrosine, Angiotensin II, atrial natriuretic peptide, adenosine, ATP, nitric oxide, carbon monoxide, arachidonic acid and derivant thereof (prostaglandins), neurosteroid, thyroliberin (ACTH), thyrotropin (TSH), chorionic-gonadotropin hormone (CG), lutropin (LH), follicle stimulating hormone (FSH), prolacrin (PRL), corticotropin releasing hormone (CRH), growth hormone releasing hormone (CHRH), parathyroid hormone-related protein, insulin like growth factor;
(2) cytokine: interferons (IFN-α, IFN-β, IFN-γ), interleukin class (IL) IL-(1~18), tumor necrosis factor (TNF-α, TNF-β), colony stimulating factor (granulocyte-CSF, macrophage-CSF, grain macrophage-CSF), erythropoietin, transforming growth factor (TGF-α, TGF-β).
(3) receptor comprises: cell surface receptor (ion channel receptor, G protein coupling receptor, tyrosine protein kinase coupling receptor, enzymatic activity receptor) and intracellular receptor.
(4) intracellular signal transduction pathway comprises: Ras protein signal path, the Rho path, the signal pipeline of second messenger system, the receptor tyrosine kinase signal transduction pathway, nonreceptor tyrosine kinase signal pathway (Src nonreceptor tyrosine kinase signal pathway, Bcr/Abl nonreceptor tyrosine kinase signal pathway, the JAK-STAT signal transduction pathway), receptor coupling connection serine/threonine kinase signal transduction (TGF-β/Smad signal transduction pathway), phosphatidylinositol 3-kinase (PI3K)-AKT path, the adhesion molecule signal pathway, the nuclear receptor signal transduction, the Wnt signal transduction, the MAPK signal transduction pathway, the apoptosis signal pathway, the cell cycle regulating signal pathway, Notch signal transduction pathway etc.
The inventor has totally investigated effect and the mechanism of these informational molecules in the morbidity of vascular lesion in conjunction with modern medicine, and specifically studies and estimated the effect of medicine in the treatment vascular lesion that influences these biomolecule.
Specifically, through studying for a long period of time, the inventor has filtered out the seven class medicines that act on above-mentioned NEI network information molecule from Chinese medicine, this seven classes medicine is respectively: flourish channels class, the smooth network class of gas, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, dispelling wind and removing obstruction in the collateral class, the dispelling toxins and dredging collaterals class medicine of supporting; And find that these Chinese medicines or Chinese medicine composition can play treatment vascular lesion, the especially effect of cardiovascular and cerebrovascular disease by acting on above one or more informational molecule or receptor or passage, and, can bring into play better therapeutical effect by this seven classes medicine is carried out various combination.
Therefore, one aspect of the present invention relates to and is selected from flourish channels class, the smooth network class of gas of supporting, the disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, the dispelling wind and removing obstruction in the collateral class, the application of one or more medicines of dispelling toxins and dredging collaterals apoplexy due to endogenous wind in the medicine of preparation treatment vascular lesion, wherein:
The flourish channels apoplexy due to endogenous wind medicated bag of supporting is drawn together: the Radix Astragali, Cornu Cervi Pantotrichum, Colla Corii Asini, Radix Adenophorae (Radix Glehniae), Radix Ophiopogonis, Placenta Hominis, Radix Aconiti Lateralis Preparata, Cortex Cinnamomi, Rhizoma Zingiberis, Radix Rehmanniae, Radix Panacis Quinquefolii, Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Rhizoma Dioscoreae, Radix Glycyrrhizae, Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Radix Polygoni Multiflori, Herba Dendrobii, Fructus Lycii, Fructus Ligustri Lucidi, Herba Taxilli, Herba Epimedii, Radix Morindae Officinalis, Herba Cistanches, Semen Cuscutae, the Cortex Eucommiae, Radix Dipsaci, Herba Epimedii, Radix Achyranthis Bidentatae.
The smooth network apoplexy due to endogenous wind of gas medicated bag is drawn together: Bulbus Allii Macrostemonis, Lignum Dalbergiae Odoriferae, Olibanum, Ramulus Cinnamomi, Lignum Santali Albi, Herba Asari, Moschus, Borneolum Syntheticum, Semen Strychni, Herba Ephedrae, Flos Inulae, Herba Menthae, Folium Mori, Flos Chrysanthemi, Radix Bupleuri, Rhizoma Cimicifugae, Herba Pogostemonis, Herba Eupatorii, Cortex Magnoliae Officinalis, Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride, the Radix Aucklandiae, Rhizoma Cyperi, Fructus Aurantii Immaturus.
Disperse blood stasis and dredge collateral apoplexy due to endogenous wind medicated bag is drawn together: Hirudo, Eupolyphaga Seu Steleophaga, Caulis Spatholobi, Radix Angelicae Sinensis, Semen Persicae, Tabanus, Radix Et Rhizoma Rhei, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Flos Carthami, Rhizoma Corydalis, Radix Curcumae, Herba Leonuri, Radix Achyranthis Bidentatae, Radix Notoginseng, Cortex Acanthopancis, Cortex Moutan, Rhizoma Corydalis, Olibanum, Myrrha, Bombyx Batryticatus, Fructus Polygoni Orientalis, Semen Vaccariae, Oletum Trogopterori, Rhizoma Corydalis.
Resolving mass and removing the obstruction of the collateral apoplexy due to endogenous wind medicated bag is drawn together: Carapax Trionycis, Rhizoma Curcumae, Squama Manis, rhizoma sparganic, Semen Crataegi, Semen Citri Reticulatae, Nidus Vespae, the speckle insect destructive of the roots of seedlings, Concha Ostreae, Os Draconis, Sanguis Draxonis, Ramulus Euonymi, Sargassum, Thallus Laminariae (Thallus Eckloniae).
The collateral dredging apoplexy due to endogenous wind medicated bag that eliminates the phlegm is drawn together Rhizoma Typhonii, Semen Sinapis Albae, Succus Bambusae, Fructus Gleditsia, Rhizoma Arisaematis, Concretio Silicea Bambusae, Retinervus Luffae Fructus, Rhizoma Atractylodis, Fructus Amomi Rotundus, Fructus Amomi, Semen Alpiniae Katsumadai, the Rhizoma Pinelliae, Semen Armeniacae Amarum, Radix Platycodonis, Flos Farfarae, Fructus Perillae, Bulbus Fritillariae Uninbracteatae, Folium Eriobotryae.
Dispelling wind and removing obstruction in the collateral apoplexy due to endogenous wind medicated bag is drawn together Ramulus Uncariae Cum Uncis, Scolopendra, Pheretima, Bombyx Batryticatus, Cornu Saigae Tataricae, Scorpio, Periostracum Cicadae, Zaocys, Radix Tripterygii Wilfordii, Caulis Lonicerae, Caulis Sinomenii, Caulis Piperis Kadsurae, Caulis Trachelospermi, Herba Aristolochiae, Flos Chrysanthemi, Herba Schizonepetae, Radix Saposhnikoviae, Folium Perillae, Rhizoma Gastrodiae, Concha Haliotidis, Rhizoma Et Radix Notopterygii, Radix Angelicae Pubescentis, Radix Clematidis, Radix Gentianae Macrophyllae.
Dispelling toxins and dredging collaterals apoplexy due to endogenous wind medicated bag is drawn together Calculus Bovis, Rhizoma Smilacis Glabrae, Gypsum Fibrosum, the Rhizoma Anemarrhenae, Cornu rhinocerotis, Radix Gentianae, Spica Prunellae, Flos Lonicerae, Fructus Forsythiae, Radix Isatidis, Folium Isatidis, Herba Taraxaci, Radix Scutellariae, Rhizoma Coptidis, Cortex Phellodendri, Fructus Gardeniae, the Radix Pulsatillae, Radix Scrophulariae, Radix Paeoniae Rubra, Herba Hedyotidis Diffusae.
Another aspect of the present invention relates to providing and can be used for treating vascular lesion, for example hypertension, coronary heart disease, diabetes, hyperlipemia and clinically with the pharmaceutical composition of diseases associated such as arteriosclerosis, thrombosis, microcirculation disturbance, at least two classes (comprising two classes) that belong to comprising of Chinese medicine composition of above seven apoplexy due to endogenous wind, each class has at least a Chinese medicine, for example a kind of, two or more Chinese medicines.
Under all situations of Chinese medicine composition, the weight ratio of any two kinds of raw material of Chinese medicine can be 0.1-2: 0.1-2 in the compositions, preferred 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2, for example, a kind of Chinese medicine composition comprises A and B, and the weight ratio of A and B can be 0.1-2: 0.1-2 so, preferred 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2.If a kind of Chinese medicine composition comprises that the weight ratio of A, B and three kinds of raw material, A so: B: C of C can be 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2, the rest may be inferred.
According to a preferred embodiment, Chinese medicine composition of the present invention comprises and is selected from least a of flourish each apoplexy due to endogenous wind of supporting channels class and disperse blood stasis and dredge collateral class.
According to a preferred embodiment of the invention, Chinese medicine composition of the present invention comprises at least a of each apoplexy due to endogenous wind of being selected from eliminate the phlegm collateral dredging class and dispelling wind and removing obstruction in the collateral class.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, each apoplexy due to endogenous wind of smooth network class of gas and disperse blood stasis and dredge collateral class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the smooth network class of gas, disperse blood stasis and dredge collateral class, each apoplexy due to endogenous wind of the collateral dredging class of eliminating the phlegm and dispelling wind and removing obstruction in the collateral class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, the smooth network class of gas, disperse blood stasis and dredge collateral class, each apoplexy due to endogenous wind of the collateral dredging class of eliminating the phlegm and dispelling wind and removing obstruction in the collateral class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, dispelling wind and removing obstruction in the collateral class, each apoplexy due to endogenous wind of dispelling toxins and dredging collaterals class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, the smooth network class of gas, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, each apoplexy due to endogenous wind of dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, the smooth network class of gas, each class of disperse blood stasis and dredge collateral class and resolving mass and removing the obstruction of the collateral class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, the smooth network class of gas, disperse blood stasis and dredge collateral class, each apoplexy due to endogenous wind of the resolving mass and removing the obstruction of the collateral class and the collateral dredging class of eliminating the phlegm at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, the smooth network class of gas, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, each apoplexy due to endogenous wind of the collateral dredging class of eliminating the phlegm and dispelling wind and removing obstruction in the collateral class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the smooth network class of gas, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, each apoplexy due to endogenous wind of dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, each apoplexy due to endogenous wind of dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, each apoplexy due to endogenous wind of dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the collateral dredging class of eliminating the phlegm, each apoplexy due to endogenous wind of dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises at least a of each apoplexy due to endogenous wind of being selected from dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, disperse blood stasis and dredge collateral class, each apoplexy due to endogenous wind of resolving mass and removing the obstruction of the collateral class and dispelling toxins and dredging collaterals class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, each apoplexy due to endogenous wind of the collateral dredging class of eliminating the phlegm and dispelling wind and removing obstruction in the collateral class at least a.
According to another preferred embodiment of the present invention, Chinese medicine composition of the present invention comprises and is selected from the flourish channels class of supporting, the smooth network class of gas, disperse blood stasis and dredge collateral class, each apoplexy due to endogenous wind of resolving mass and removing the obstruction of the collateral class and dispelling wind and removing obstruction in the collateral class at least a.
According to a preferred embodiment, Chinese medicine composition of the present invention comprises Radix Ginseng and Radix Salviae Miltiorrhizae, and the weight ratio of the two is 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2.
According to another preferred embodiment, Chinese medicine composition of the present invention comprises Scolopendra+Rhizoma Pinelliae+Scorpio, three's weight ratio is 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2.
According to another preferred embodiment, Chinese medicine composition of the present invention comprises Scolopendra+Rhizoma Arisaematis+Caulis Spatholobi+Fructus Aurantii Immaturus, four weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2.
According to another preferred embodiment, Chinese medicine composition of the present invention comprises Scolopendra+Rhizoma Pinelliae+Hirudo+Radix Ginseng+Ramulus Cinnamomi, five weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2.
According to another preferred embodiment, Chinese medicine composition of the present invention comprises the Radix Astragali+Rhizoma Smilacis Glabrae+Radix Angelicae Pubescentis+Rhizoma Chuanxiong+Carapax Trionycis+Rhizoma Arisaematis, six weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2.
According to another preferred embodiment, Chinese medicine composition of the present invention comprises Scolopendra+Rhizoma Pinelliae+Hirudo+Radix Ginseng+Ramulus Cinnamomi+Carapax Trionycis+Radix Paeoniae Rubra, wherein seven weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2.
Can prepare Chinese medicine composition of the present invention according to a conventional method, for example can get the filtrate merging of each time and make oral liquid by various raw materials are boiled one or many with the decocting of the 200%-1000% of raw material gross weight; Perhaps, make powder, or make the honeyed pill or the watered pill by with various raw material pulverizing; Perhaps boil one or many by the decocting that various raw materials is added the 200%-1000% of raw material gross weight, the filtrate of getting each time merges, and concentrates, and makes concentrated pill or capsule; After perhaps for example ethanol, acetone etc. extract the effective ingredient of various raw materials by water or organic solvent, again all effective ingredient are merged, make suitable dosage form with excipient, for example granular preparation or injection formulation.
Chinese medicine composition of the present invention can take any dosage form that is suitable for clinical practice such as oral liquid, capsule, tablet, decoction pieces, injection, pill, concentrate formulation, granular preparation to exist.Chinese medicine composition of the present invention is not limited to any particular dosage form.
The Chinese medicine type combination of compositions can decide according to tcm clinical practice is dialectical.For example, clinical syndrome differentiation is QI and blood deficiency and stagnation of heart-blood, can adopt flourish support channels class and and the combination of disperse blood stasis and dredge collateral class medicine.Clinical syndrome differentiation is that expectorant turbidly is jammed, blood vessels stagnate the person, can adopt the Chinese medicine composition of eliminate the phlegm collateral dredging class and dispelling wind and removing obstruction in the collateral class.To be that expectorant is turbid be jammed clinical syndrome differentiation, and ailment said due to cold or exposure, the evil invasion and attack of poison channels can adopt the collateral dredging class of eliminating the phlegm, the Chinese medicine composition of dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class.
The dosage of Chinese medicine composition of the present invention is not special restriction, but can decide according to patient's body weight, age, disease specific, dosage form, doctor's clinical experience, but dosage is 5-400g raw material dose summation/day usually, preferred 30-200g raw material dose summation/day can be in single or divided doses.
The specific embodiment
Below to content involved in the present invention in conjunction with following specific embodiment and pharmacological testing content, be elaborated one by one.
Embodiment 1 one classes belong to flourish and support the channels class and pass through to regulate the Chinese medicine of NEI network with the treatment vascular conditions
The flourish channels medicine of supporting is grown negative and positive of qi and blood deficiency in the flourish replenishing vital QI with drugs of warm nature network mainly based on tonic, is mainly used in the not flourish card of network void.This type of medicine is representative with the Radix Ginseng, also comprises: the Radix Astragali, Cornu Cervi Pantotrichum, Colla Corii Asini, Radix Adenophorae (Radix Glehniae), Radix Ophiopogonis, Placenta Hominis, Radix Aconiti Lateralis Preparata, Cortex Cinnamomi, Rhizoma Zingiberis, Radix Rehmanniae, Radix Panacis Quinquefolii, Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Rhizoma Dioscoreae, Radix Glycyrrhizae, Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Radix Polygoni Multiflori, Herba Dendrobii, Fructus Lycii, Fructus Ligustri Lucidi, Herba Taxilli, Herba Epimedii, Radix Morindae Officinalis, Herba Cistanches, Semen Cuscutae, the Cortex Eucommiae, Radix Dipsaci, Herba Epimedii, Radix Achyranthis Bidentatae.
Medicine is represented in test: Radix Ginseng
The experiment exercise question: Radix Ginseng is to the influence of rats with acute myocardial infarction sympathetic nerve mediator and renin-angiotensin system
Purpose: observe the influence of Radix Ginseng to rats with acute myocardial infarction sympathetic nerve mediator and renin-angiotensin system (RAS).
Method: cause the myocardial infarction animal model by rat ligation ramus descendens anterior arteriae coronariae sinistrae (LAD), measure myocardial infarction area, serum norepinephrine (NE) and epinephrine (E) content, serum angiotensin converting enzyme (ACE) and plasma renin (R) activity.
The result: Radix Ginseng to acute myocardial infarction after the 24h rat can obviously dwindle myocardial infarction area, obviously reduce serum N E, E content and serum serum ACE and blood plasma R activity.
Conclusion: Radix Ginseng has protective effect to acute myocardial ischemia, may-adrenal medulla sympathetic with its inhibition be overexcited, and minimizing catecholamine (CA) is secreted in a large number and suppressed RAS and activate, and reduces Angiotensin II and generates, and the mechanism of regulating the NEI network is relevant.
Embodiment 2 one classes belong to the smooth network class of gas and pass through to regulate the Chinese medicine of NEI network with the treatment vascular conditions
The smooth network class of gas mainly adopts the hot fragrant gas of acrid, and unobstructed network gas is mainly used in the network stagnation of QI that treatment runs in the gas network and stagnates, and also the blood operation of venation is had the smooth effect of dredging simultaneously.This type of medicine is the representative medicine with Bulbus Allii Macrostemonis, Lignum Dalbergiae Odoriferae, also comprises: Olibanum, Ramulus Cinnamomi, Lignum Santali Albi, Herba Asari, Moschus, Borneolum Syntheticum, Semen Strychni, Herba Ephedrae, Flos Inulae, Herba Menthae, Folium Mori, Flos Chrysanthemi, Radix Bupleuri, Rhizoma Cimicifugae, Herba Pogostemonis, Herba Eupatorii, Cortex Magnoliae Officinalis, Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride, the Radix Aucklandiae, Rhizoma Cyperi, Fructus Aurantii Immaturus.
Medicine is represented in test: Radix Bupleuri
The experiment exercise question: Radix Bupleuri is to the influence of Hypertensive Rats neuroendocrine-immune system
Purpose: observe the influence of Radix Bupleuri, treat hypertensive mechanism of action to inquire into Radix Bupleuri to multinomial microcosmic indexs such as Hypertensive Rats nerve, endocrine, immunity.
Method: all animals all are divided into two groups at random in 1: 1 ratio, experimental group and blank group, and be 1 month the course of treatment.Experiment adopts high performance chromatograph to measure plasma norepinephrine (NE), epinephrine (E), dopamine (DA)
Content; Employing is put and is exempted from method mensuration blood plasma beta-endorphin, ET, NO, calcitonin-gene-related peptide, neuropeptide tyrosine etc.; Adopt laser light scattering turbidimetry for Determination blood plasma immunoglobulin IgG, IgA;
The result: vaso-excitor materials such as the NE of experimental group, ET, neuropeptide tyrosine, beta-endorphin reduce; And expansion angiogenic substance content such as epinephrine, dopamine, NO, calcitonin-gene-related peptide increase by two groups of there was no significant differences of blood plasma immunoglobulin IgG, IgA.
Conclusion: Radix Bupleuri may be by regulating neuroendocrine system, improves the diastolic function of blood vessel and plays hypotensive effect.
Embodiment 3 one classes belong to the disperse blood stasis and dredge collateral class and pass through to regulate the Chinese medicine of NEI network with the treatment vascular conditions
The disperse blood stasis and dredge collateral medicine is mainly used in the resistance of the channels stasis of blood, on behalf of medicine, it Hirudo, Caulis Spatholobi, Eupolyphaga Seu Steleophaga are arranged, and also comprises: Radix Angelicae Sinensis, Semen Persicae, Tabanus, Radix Et Rhizoma Rhei, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Flos Carthami, Rhizoma Corydalis, Radix Curcumae, Herba Leonuri, Radix Achyranthis Bidentatae, Radix Notoginseng, Cortex Acanthopancis, Cortex Moutan, Rhizoma Corydalis, Olibanum, Myrrha, Bombyx Batryticatus, Fructus Polygoni Orientalis, Semen Vaccariae, Oletum Trogopterori, Rhizoma Corydalis.
Medicine is represented in test: Eupolyphaga Seu Steleophaga
The experiment exercise question: Eupolyphaga Seu Steleophaga is to the influence of experimental atherosclerosis rabbit vascular endothelium dysfunction
Purpose: observe the influence of Eupolyphaga Seu Steleophaga to experimental atherosclerosis rabbit vascular endothelium dysfunction;
Method: duplicate the rabbit Atherosclerosis Model, measure the damage of endotheliocyte anti-peroxidation, antithrombotic forms, and the vasoactive polypeptide expression;
The result: Eupolyphaga Seu Steleophaga can reduce serum lipid peroxide content, rising blood plasma prostaglandin (PGI 2), nitric oxide (NO) and calcitonin-gene-related peptide level, reduce thromboxane A 2(TXA 2) level, but and the overexpression of antagonism Endothelin-mRNA (ET-mRNA) endotheliocyte (EC), smooth muscle cell (SMC), macrophage in aortic tunica intima;
Conclusion: the prompting Eupolyphaga Seu Steleophaga may be one of important mechanisms of its study of anti-atherogenic effect by the informational molecule in the NEI network being regulated and then being improved vascular endothelial function.
Embodiment 4 one classes belong to the resolving mass and removing the obstruction of the collateral class and pass through to regulate the Chinese medicine of NEI network with the treatment vascular conditions
The resolving mass and removing the obstruction of the collateral medicine is usually used in pathogen and delays channels, and the turbid cohesion of blood stasis and expectorant is shaped to cease and forms long-pending pathological changes.On behalf of medicine, it Carapax Trionycis, Rhizoma Curcumae are arranged, and also comprises: Squama Manis, rhizoma sparganic, Semen Crataegi, Semen Citri Reticulatae, Nidus Vespae, the speckle insect destructive of the roots of seedlings, Concha Ostreae, Os Draconis, Sanguis Draxonis, Ramulus Euonymi, Sargassum, Thallus Laminariae (Thallus Eckloniae).
Medicine is represented in test: Rhizoma Curcumae
Experiment exercise question: the atherosclerotic research of Rhizoma Curcumae water extract Chinese People's Anti-Japanese Military and Political College Mus
Purpose: observe the antiatherogenic effect of Rhizoma Curcumae water extract;
Method: adopt classical nursing method to duplicate the atherosclerotic model of rabbit, feed high lipid food, irritate continuous 12 weeks of stomach Rhizoma Curcumae water extract simultaneously.Experiment finishes the back blood sampling and measures nitric oxide, P material, Endothelin, VEGF (VEGF), interleukin 3, interleukin 8, M-CSF (MCSF) and tumor necrosis factor (TNF-α);
Result: Rhizoma Curcumae can obviously raise serum levels of nitric oxide, P material, reduce serum endothelin, VEGF (VEGF), interleukin 3, the level of interleukin 8, M-CSF (MCSF) and tumor necrosis factor (TNF-α);
Conclusion: Rhizoma Curcumae water extract can be by regulating informational molecules such as neurotransmitter in the NEI network, cytokine, and the inflammation-inhibiting reaction improves vascular endothelial function and brings into play antiatherogenic effect.
Embodiment 5 one classes belong to eliminates the phlegm the collateral dredging class and passes through to regulate the Chinese medicine of NEI network with the treatment vascular conditions
The collateral dredging class of eliminating the phlegm medicine is usually used in the channels stasis of blood resistance based on phlegm-damp.Its representative drugs has Rhizoma Typhonii, Semen Sinapis Albae, Succus Bambusae, also comprises: Fructus Gleditsia, Rhizoma Arisaematis, Concretio Silicea Bambusae, Retinervus Luffae Fructus, Rhizoma Atractylodis, Fructus Amomi Rotundus, Fructus Amomi, Semen Alpiniae Katsumadai, the Rhizoma Pinelliae, Semen Armeniacae Amarum, Radix Platycodonis, Flos Farfarae, Fructus Perillae, Bulbus Fritillariae Uninbracteatae, Folium Eriobotryae.
Medicine is represented in test: Concretio Silicea Bambusae
The experiment exercise question: Concretio Silicea Bambusae is to the research of hyperlipemia hyperamization endothelial cell damaging action
Purpose: observe the influence of Concretio Silicea Bambusae to the damage of hyperlipemia hyperamization endothelial cell;
Method: select healthy male Japan large ear rabbit for use, be divided into matched group, model group, Chinese drug-treated group at random, give with animal high fat diet nursing and set up hyperlipemia model, after the model success, Chinese drug-treated group gives the Concretio Silicea Bambusae water extract and irritates stomach, each is organized in 6 weeks back execution animal, gather animal blood and thoracic aorta specimen, detect indexs such as low density lipoprotein, LDL, high density lipoprotein, monocyte chemoattractant protein-1, c reactive protein, ICAIU, Endothelin and receptor expression, gamma interferon;
The result: Chinese drug-treated group is compared with model group, and high density lipoprotein, gamma interferon in its blood and the tissue raise obviously, and monocyte chemoattractant protein-1, c reactive protein, ICAIU, Endothelin and receptor expression are reduction in various degree;
Conclusion: Concretio Silicea Bambusae causes injury of vascular endothelial cells to hyperlipemia and has significant protective effect, and this protective effect may realize by regulating the NEI network.
Embodiment 6 one classes belong to the dispelling wind and removing obstruction in the collateral class and pass through to regulate the Chinese medicine of NEI network with the treatment vascular conditions
Dispelling wind and removing obstruction in the collateral class medicine be utilization hot loose dispel the wind or the endogenous wind stopping relieving convulsion go into the network medicine, disease such as the treatment ailment said due to cold or exposure attacks tic, spasm due to the network, shake, tremble.Its representational medicine has Ramulus Uncariae Cum Uncis, Scolopendra, Pheretima, also comprises: Bombyx Batryticatus, Cornu Saigae Tataricae, Scorpio, Periostracum Cicadae, Zaocys, Radix Tripterygii Wilfordii, Caulis Lonicerae, Caulis Sinomenii, Caulis Piperis Kadsurae, Caulis Trachelospermi, Herba Aristolochiae, Flos Chrysanthemi, Herba Schizonepetae, Radix Saposhnikoviae, Folium Perillae, Rhizoma Gastrodiae, Concha Haliotidis, Rhizoma Et Radix Notopterygii, Radix Angelicae Pubescentis, Radix Clematidis, Radix Gentianae Macrophyllae.
Medicine is represented in test: Pheretima
Experiment exercise question: the atherosclerotic research of the anti-rabbit of Pheretima
Purpose: observe the antiatherogenic effect of aqueous extract of earthworm;
Method: adopt classical nursing method to duplicate the atherosclerotic model of rabbit, feed high lipid food, irritate continuous 12 weeks of stomach aqueous extract of earthworm simultaneously, experiment finishes the ear blood sampling and measures carbon monoxide, Endothelin, Angiotensin II, neuropeptide tyrosine, interleukin II, interleukin 10 is observed pathology, and flow cytometer detects the smooth muscle cell proliferation cycle;
The result: Pheretima can obviously raise serum carbon monoxide and interleukin 10 level, reduce Endothelin, Angiotensin II, neuropeptide tyrosine and interleukin II, suppress division, the propagation of vascular smooth muscle cell;
Conclusion: Pheretima can be improved vascular endothelial function by regulating the expression of the total informational molecule in the NEI network, suppresses the propagation of vascular smooth muscle and brings into play antiatherogenic effect.
Embodiment 7 one classes belong to the dispelling toxins and dredging collaterals class and by regulating the NEI network with the Chinese medicine of treatment vascular conditions or contain the combination medicine of this type of Chinese medicine
The dispelling toxins and dredging collaterals class is usually used in the disease that malicious heresy stagnates and causes in channels.Its representational medicine has Calculus Bovis, also comprises: Rhizoma Smilacis Glabrae, Gypsum Fibrosum, the Rhizoma Anemarrhenae, Cornu rhinocerotis, Radix Gentianae, Spica Prunellae, Flos Lonicerae, Fructus Forsythiae, Radix Isatidis, Folium Isatidis, Herba Taraxaci, Radix Scutellariae, Rhizoma Coptidis, Cortex Phellodendri, Fructus Gardeniae, the Radix Pulsatillae, Radix Scrophulariae, Radix Paeoniae Rubra, Herba Hedyotidis Diffusae.
Medicine is represented in test: Rhizoma Smilacis Glabrae
The experiment exercise question: Rhizoma Smilacis Glabrae is to the effect of diabetic nephropathy rat neuroendocrine system
Purpose: observe the regulating action of Rhizoma Smilacis Glabrae to diabetic nephropathy rat neuroendocrine system;
Method: utilize tail vein injection streptozotocin (STZ) method, set up the diabetes rat animal model, the research Rhizoma Smilacis Glabrae is to the influence of indexs such as rat blood sugar, glucagon, pituitary growth hormone, erythrocyte immune adhesion, hypothalamus neurotransmitter;
The result: Rhizoma Smilacis Glabrae has effects such as the blood plasma of reduction glucagon, pituitary growth hormone, raising erythrocyte immune adhesion function, and the realization of this effect enlivens relevant with inhibition hypothalamus dopaminergic neuron and adrenergic neuron dysfunction.
Conclusion: by neuroendocrine function in the adjusting NEI network and erythrocyte immune adhesion function is one of important mechanisms of Rhizoma Smilacis Glabrae treatment diabetic nephropathy.
Embodiment 8 one classes are by regulating the NEI network with one or more the Chinese medicine composition medicine in the optional two class medicines in the seven class medicines of treatment vascular conditions
Medicine is represented in test: Radix Ginseng+Radix Salviae Miltiorrhizae (1: 1)
Purpose: observe of the influence of this compound recipe to rats with acute myocardial infarction sympathetic nerve mediator and renin-angiotensin system (RAS).
Method: cause the myocardial infarction animal model by rat ligation ramus descendens anterior arteriae coronariae sinistrae (LAD), measure myocardial infarction area, serum norepinephrine (NE) and epinephrine (E) content, serum angiotensin converting enzyme (ACE) and plasma renin (R) activity.
The result: this compound recipe to acute myocardial infarction after the 24h rat can obviously dwindle myocardial infarction area, obviously reduce serum N E, E content and serum ACE and blood plasma R activity.
Conclusion: this compound recipe has protective effect to acute myocardial ischemia, may-adrenal medulla sympathetic with its inhibition be overexcited, and minimizing catecholamine (CA) is secreted in a large number and suppressed RAS and activate, and reduces Angiotensin II and generates, and it is relevant to regulate the NEI network mechanism.
Embodiment 9 one classes are by regulating the NEI network with one or more the Chinese medicine composition medicine in the optional three class medicines in the seven class medicines of treatment vascular conditions
Medicine is represented in experiment: Scolopendra+Rhizoma Pinelliae+Scorpio (2: 1: 2)
Purpose: observe the antiatherogenic effect of this compound recipe;
Method: adopt classical nursing method to duplicate the atherosclerotic model of rabbit, feed high lipid food, irritate continuous 12 weeks of this compound recipe of stomach simultaneously, experiment finishes the ear blood sampling and measures nitric oxide, Endothelin, Angiotensin II, neuropeptide tyrosine, interleukin II, interleukin 10 is observed pathology, and flow cytometer detects the smooth muscle cell proliferation cycle;
The result: this compound recipe can obviously raise serum levels of nitric oxide and interleukin 10 level, reduce Endothelin, Angiotensin II, neuropeptide tyrosine and interleukin II, suppress division, the propagation of vascular smooth muscle cell;
Conclusion: this compound recipe can improve vascular endothelial function by regulating the total informational molecule in the NEI network, suppresses the propagation of vascular smooth muscle and brings into play antiatherogenic effect.
Embodiment 10 1 classes are by regulating the NEI network with one or more the Chinese medicine composition medicine in the optional four class medicines in the seven class medicines of treatment vascular conditions
Medicine is represented in test: Scolopendra+Rhizoma Arisaematis+Caulis Spatholobi+Fructus Aurantii Immaturus (1: 1: 3: 2)
Purpose: observe this compound recipe to the influence of NEI network in the coronary vasospasm regulating action;
Method: select healthy Japan large ear rabbit for use, be divided into matched group at random, the spasm group, the collateral dredging group, after around the utilization high fat diet is fed, auricular vein injection ergometrine is set up the coronary spasm model, and after injection 0.5h, 1h, 4h, 8h, 12h, 24h puts to death animal respectively, gather blood, the coronary artery specimen, detect Endothelin (ET) in blood and the tissue, norepinephrine (NE), nitric oxide (NO), neuropeptide tyrosine, vasopressin (AVP), tumor necrosis factor, il-1, the variation of the indexs such as activity of endothelial nitric oxide synthase (eNOS), immunohistochemical method detects the expression of endothelial nitric oxide synthase (eNOS) and Angiotensin-Converting (ACE);
Result: compare with the spasm group, levels such as ET, the NE in collateral dredging group blood and the tissue, ACE, neuropeptide tyrosine, AVP, tumor necrosis factor, il-1 have reduction in various degree, the NO level raises to some extent, and eNOS expresses and is strong positive in the arterial endothelium tissue, and the ACE expression weakens to some extent;
Conclusion: this compound recipe can be alleviated coronary vasospasm to a certain extent, and its mechanism that plays a role may be relevant with adjusting NEI network.
Embodiment 11 1 classes are by regulating the NEI network with one or more the Chinese medicine composition medicine in the optional five class medicines in the seven class medicines of treatment vascular conditions
Medicine is represented in test: Scolopendra+Rhizoma Pinelliae+Hirudo+Radix Ginseng+Ramulus Cinnamomi (2: 1: 2: 1: 3)
Purpose: observe the curative effect of this compound recipe to the rat chronic myocardial infarction model;
Method: select the SD rat for use, be divided into matched group, model group and collateral dredging group at random, the utilization high fat diet adds the narrow method of Ameroid garlands rugosity and sets up the chronic myocardial infarction model, irritate stomach in giving compound recipe two weeks (when blood fat increases) with above three kinds of medicines, and respectively at putting to death animal collection blood and thoracic aorta, heart preparation 4,8,12,16 weeks, the area of myocardial infarction is observed in the variation of nitric oxide in detection blood plasma and the tissue, SOD, MDA, ET, Angiotensin II, IL-10, IL-6 etc., light microscopic down;
The result: compare with model group, the area of myocardial infarction reduces to some extent under the collateral dredging group light microscopic, and nitric oxide in blood plasma and the aortic tissue, IL-10 content, SOD is active obviously raises, and MDA, ET, Angiotensin II, IL-6 level significantly reduce;
Conclusion: this compound recipe has certain effect to chronic myocardial infarction, and its mechanism that plays a role is to realize by the informational molecule of regulating in the NEI network.
Embodiment 12 1 classes are by regulating the NEI network with one or more the Chinese medicine composition medicine in the optional six class medicines in the seven class medicines of treatment vascular conditions
Medicine is represented in test: the Radix Astragali+Rhizoma Smilacis Glabrae+Radix Angelicae Pubescentis+Rhizoma Chuanxiong+Carapax Trionycis+Rhizoma Arisaematis (1: 2: 1: 2: 0.5: 2)
Purpose: observe this compound recipe to the regulating action of diabetic nephropathy rat neuroendocrine system and the influence of erythrocyte immune adhesion function;
Method: utilize tail vein injection streptozotocin (STZ) method, set up the diabetes rat animal model, study of the influence of this compound recipe to indexs such as rat blood sugar, glucagon, pituitary growth hormone, erythrocyte immune adhesion, hypothalamus neurotransmitteies;
The result: this compound recipe has effects such as the fasting glucose of reduction, blood plasma glucagon, pituitary growth hormone, raising erythrocyte immune adhesion function, and the realization of this effect enlivens relevant with inhibition hypothalamus dopaminergic neuron and adrenergic neuron dysfunction.
Conclusion: by neuroendocrine function and erythrocyte immune adhesion function in the adjusting NEI network is one of important mechanisms of this compound treatment diabetic nephropathy.
Embodiment 13 1 classes are by regulating the NEI network with one or more the Chinese medicine composition medicine in the optional seven class medicines in the seven class medicines of treatment vascular conditions
Medicine is represented in test: Scolopendra+Rhizoma Pinelliae+Hirudo+Radix Ginseng+Ramulus Cinnamomi+Carapax Trionycis+Radix Paeoniae Rubra (2: 1: 2: 2: 1: 0.5: 1)
Purpose: observe the curative effect of this compound recipe to the rat chronic myocardial infarction model;
Method: select the SD rat for use, be divided into matched group, model group and collateral dredging group at random, the utilization high fat diet adds the narrow method of Ameroid garlands rugosity and sets up the chronic myocardial infarction model, irritate stomach in giving compound recipe two weeks (when blood fat increases) with above three kinds of medicines, and respectively at putting to death animal collection blood and thoracic aorta, heart preparation 4,8,12,16 weeks, the area of myocardial infarction is observed in the variation of nitric oxide in detection blood plasma and the tissue, SOD, MDA, ET, Angiotensin II, IL-10, IL-6 etc., light microscopic down;
The result: compare with model group, the area of myocardial infarction reduces to some extent under the collateral dredging group light microscopic, and nitric oxide in blood plasma and the aortic tissue, IL-10 content, SOD is active obviously raises, and MDA, ET, Angiotensin II, IL-6 level significantly reduce;
Conclusion: this compound recipe has certain effect to chronic myocardial infarction, and its mechanism that plays a role may be to realize by the informational molecule of regulating in the NEI network.
Above according to for example clear the present invention of specific embodiments, but it will be apparent to those skilled in that, under situation without departing from the spirit and scope of the present invention, can on basis of the present invention, make many variations and change, these variations and change comprise within the scope of the invention.

Claims (10)

1. the medicine of the known signal transduction pathway that can actively act on the total informational molecule of nerve-endocrine-immune system network (NEI network) and receptor thereof or total informational molecule of influence and receptor thereof is in preparation treatment vascular lesion, the especially application in the medicine of cardiovascular and cerebrovascular disease.
2. according to the application of claim 1, wherein said medicine comprises that one or more are selected from the material of single medicinal material, Chinese medicine composition and preparation thereof, chemical effective ingredient, Pharmaceutical composition and preparation, biological effective components, Pharmaceutical composition and preparation thereof.
3. according to the application of claim 2, wherein said medicine comprises that a class or multiclass are selected from the single medicinal material of following classification, Chinese medicine composition and preparation thereof: flourish channels class, the smooth network class of gas of supporting, the disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, the dispelling wind and removing obstruction in the collateral class, the dispelling toxins and dredging collaterals class; Each class has at least a single medicinal material, Chinese medicine composition or its preparation;
The flourish channels class single medicinal material of supporting comprises: the Radix Astragali, Cornu Cervi Pantotrichum, Colla Corii Asini, Radix Adenophorae (Radix Glehniae), Radix Ophiopogonis, Placenta Hominis, Radix Aconiti Lateralis Preparata, Cortex Cinnamomi, Rhizoma Zingiberis, Radix Rehmanniae, Radix Panacis Quinquefolii, Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Rhizoma Dioscoreae, Radix Glycyrrhizae, Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Radix Polygoni Multiflori, Herba Dendrobii, Fructus Lycii, Fructus Ligustri Lucidi, Herba Taxilli, Herba Epimedii, Radix Morindae Officinalis, Herba Cistanches, Semen Cuscutae, the Cortex Eucommiae, Radix Dipsaci, Herba Epimedii, Radix Achyranthis Bidentatae;
The smooth network class of gas single medicinal material comprises; Bulbus Allii Macrostemonis, Lignum Dalbergiae Odoriferae, Olibanum, Ramulus Cinnamomi, Lignum Santali Albi, Herba Asari, Moschus, Borneolum Syntheticum, Semen Strychni, Herba Ephedrae, Flos Inulae, Herba Menthae, Folium Mori, Flos Chrysanthemi, Radix Bupleuri, Rhizoma Cimicifugae, Herba Pogostemonis, Herba Eupatorii, Cortex Magnoliae Officinalis, Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride, the Radix Aucklandiae, Rhizoma Cyperi, Fructus Aurantii Immaturus;
Disperse blood stasis and dredge collateral class single medicinal material comprises: Hirudo, Eupolyphaga Seu Steleophaga, Caulis Spatholobi, Radix Angelicae Sinensis, Semen Persicae, Tabanus, Radix Et Rhizoma Rhei, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Flos Carthami, Rhizoma Corydalis, Radix Curcumae, Herba Leonuri, Radix Achyranthis Bidentatae, Radix Notoginseng, Cortex Acanthopancis, Cortex Moutan, Rhizoma Corydalis, Olibanum, Myrrha, Bombyx Batryticatus, Fructus Polygoni Orientalis, Semen Vaccariae, Oletum Trogopterori, Rhizoma Corydalis;
Resolving mass and removing the obstruction of the collateral class single medicinal material comprises: Carapax Trionycis, Rhizoma Curcumae, Squama Manis, rhizoma sparganic, Semen Crataegi, Semen Citri Reticulatae, Nidus Vespae, the speckle insect destructive of the roots of seedlings, Concha Ostreae, Os Draconis, Sanguis Draxonis, Ramulus Euonymi, Sargassum, Thallus Laminariae (Thallus Eckloniae);
The collateral dredging class of eliminating the phlegm single medicinal material comprises: Rhizoma Typhonii, Semen Sinapis Albae, Succus Bambusae, Fructus Gleditsia, Rhizoma Arisaematis, Concretio Silicea Bambusae, Retinervus Luffae Fructus, Rhizoma Atractylodis, Fructus Amomi Rotundus, Fructus Amomi, Semen Alpiniae Katsumadai, the Rhizoma Pinelliae, Semen Armeniacae Amarum, Radix Platycodonis, Flos Farfarae, Fructus Perillae, Bulbus Fritillariae Uninbracteatae, Folium Eriobotryae;
Dispelling wind and removing obstruction in the collateral class single medicinal material comprises: Ramulus Uncariae Cum Uncis, Scolopendra, Pheretima, Bombyx Batryticatus, Cornu Saigae Tataricae, Scorpio, Periostracum Cicadae, Zaocys, Radix Tripterygii Wilfordii, Caulis Lonicerae, Caulis Sinomenii, Caulis Piperis Kadsurae, Caulis Trachelospermi, Herba Aristolochiae, Flos Chrysanthemi, Herba Schizonepetae, Radix Saposhnikoviae, Folium Perillae, Rhizoma Gastrodiae, Concha Haliotidis, Rhizoma Et Radix Notopterygii, Radix Angelicae Pubescentis, Radix Clematidis, Radix Gentianae Macrophyllae;
Dispelling toxins and dredging collaterals class single medicinal material comprises: Calculus Bovis, Rhizoma Smilacis Glabrae, Gypsum Fibrosum, the Rhizoma Anemarrhenae, Cornu rhinocerotis, Radix Gentianae, Spica Prunellae, Flos Lonicerae, Fructus Forsythiae, Radix Isatidis, Folium Isatidis, Herba Taraxaci, Radix Scutellariae, Rhizoma Coptidis, Cortex Phellodendri, Fructus Gardeniae, the Radix Pulsatillae, Radix Scrophulariae, Radix Paeoniae Rubra, Herba Hedyotidis Diffusae.
4. thereby by the novel drugs of positive role in the signal transduction pathway treatment vascular lesion of the total said informational molecule of NEI network and receptor or said total informational molecule of positive impact and receptor thereof.
5. according to the medicine of claim 4, wherein said medicine comprises that one or more are selected from the material of single medicinal material, Chinese medicine composition and preparation thereof, chemical effective ingredient, Pharmaceutical composition and preparation, biological effective components, Pharmaceutical composition and preparation thereof.
6. according to the medicine of claim 5, wherein said medicine comprises that a class or multiclass are selected from the single medicinal material of following classification, Chinese medicine composition and preparation thereof: flourish channels class, the smooth network class of gas of supporting, the disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, the dispelling wind and removing obstruction in the collateral class, the dispelling toxins and dredging collaterals class; Each class has at least a single medicinal material, Chinese medicine composition or its preparation;
The flourish channels class single medicinal material of supporting comprises: the Radix Astragali, Cornu Cervi Pantotrichum, Colla Corii Asini, Radix Adenophorae (Radix Glehniae), Radix Ophiopogonis, Placenta Hominis, Radix Aconiti Lateralis Preparata, Cortex Cinnamomi, Rhizoma Zingiberis, Radix Rehmanniae, Radix Panacis Quinquefolii, Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, Rhizoma Dioscoreae, Radix Glycyrrhizae, Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Radix Polygoni Multiflori, Herba Dendrobii, Fructus Lycii, Fructus Ligustri Lucidi, Herba Taxilli, Herba Epimedii, Radix Morindae Officinalis, Herba Cistanches, Semen Cuscutae, the Cortex Eucommiae, Radix Dipsaci, Herba Epimedii, Radix Achyranthis Bidentatae;
The smooth network class of gas single medicinal material comprises: Bulbus Allii Macrostemonis, Lignum Dalbergiae Odoriferae, Olibanum, Ramulus Cinnamomi, Lignum Santali Albi, Herba Asari, Moschus, Borneolum Syntheticum, Semen Strychni, Herba Ephedrae, Flos Inulae, Herba Menthae, Folium Mori, Flos Chrysanthemi, Radix Bupleuri, Rhizoma Cimicifugae, Herba Pogostemonis, Herba Eupatorii, Cortex Magnoliae Officinalis, Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride, the Radix Aucklandiae, Rhizoma Cyperi, Fructus Aurantii Immaturus;
Disperse blood stasis and dredge collateral class single medicinal material comprises: Hirudo, Eupolyphaga Seu Steleophaga, Caulis Spatholobi, Radix Angelicae Sinensis, Semen Persicae, Tabanus, Radix Et Rhizoma Rhei, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Flos Carthami, Rhizoma Corydalis, Radix Curcumae, Herba Leonuri, Radix Achyranthis Bidentatae, Radix Notoginseng, Cortex Acanthopancis, Cortex Moutan, Rhizoma Corydalis, Olibanum, Myrrha, Bombyx Batryticatus, Fructus Polygoni Orientalis, Semen Vaccariae, Oletum Trogopterori, Rhizoma Corydalis;
Resolving mass and removing the obstruction of the collateral class single medicinal material comprises: Carapax Trionycis, Rhizoma Curcumae, Squama Manis, rhizoma sparganic, Semen Crataegi, Semen Citri Reticulatae, Nidus Vespae, the speckle insect destructive of the roots of seedlings, Concha Ostreae, Os Draconis, Sanguis Draxonis, Ramulus Euonymi, Sargassum, Thallus Laminariae (Thallus Eckloniae);
The collateral dredging class of eliminating the phlegm single medicinal material comprises: Rhizoma Typhonii, Semen Sinapis Albae, Succus Bambusae, Fructus Gleditsia, Rhizoma Arisaematis, Concretio Silicea Bambusae, Retinervus Luffae Fructus, Rhizoma Atractylodis, Fructus Amomi Rotundus, Fructus Amomi, Semen Alpiniae Katsumadai, the Rhizoma Pinelliae, Semen Armeniacae Amarum, Radix Platycodonis, Flos Farfarae, Fructus Perillae, Bulbus Fritillariae Uninbracteatae, Folium Eriobotryae;
Dispelling wind and removing obstruction in the collateral class single medicinal material comprises: Ramulus Uncariae Cum Uncis, Scolopendra, Pheretima, Bombyx Batryticatus, Cornu Saigae Tataricae, Scorpio, Periostracum Cicadae, Zaocys, Radix Tripterygii Wilfordii, Caulis Lonicerae, Caulis Sinomenii, Caulis Piperis Kadsurae, Caulis Trachelospermi, Herba Aristolochiae, Flos Chrysanthemi, Herba Schizonepetae, Radix Saposhnikoviae, Folium Perillae, Rhizoma Gastrodiae, Concha Haliotidis, Rhizoma Et Radix Notopterygii, Radix Angelicae Pubescentis, Radix Clematidis, Radix Gentianae Macrophyllae;
Dispelling toxins and dredging collaterals class single medicinal material comprises: Calculus Bovis, Rhizoma Smilacis Glabrae, Gypsum Fibrosum, the Rhizoma Anemarrhenae, Cornu rhinocerotis, Radix Gentianae, Spica Prunellae, Flos Lonicerae, Fructus Forsythiae, Radix Isatidis, Folium Isatidis, Herba Taraxaci, Radix Scutellariae, Rhizoma Coptidis, Cortex Phellodendri, Fructus Gardeniae, the Radix Pulsatillae, Radix Scrophulariae, Radix Paeoniae Rubra, Herba Hedyotidis Diffusae.
7. according to the medicine of claim 6, wherein said vascular lesion is meant hypertension, coronary heart disease, diabetes, hyperlipemia and clinically with diseases associated such as arteriosclerosis, thrombosis, microcirculation disturbance; The weight ratio that comprises in the said compositions, be selected from different classes of any two kinds of raw material of Chinese medicine can be 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2.
8. according to any one medicine among the claim 4-7, be selected from following combination comprising any one:
Comprise and be selected from flourish each at least a single medicinal material of each apoplexy due to endogenous wind of supporting channels class and disperse blood stasis and dredge collateral class; Or
Comprise each at least a single medicinal material of each apoplexy due to endogenous wind that is selected from eliminate the phlegm collateral dredging class and dispelling wind and removing obstruction in the collateral class; Or
Comprise and be selected from flourish each at least a single medicinal material of each apoplexy due to endogenous wind of supporting channels class, the smooth network class of gas and disperse blood stasis and dredge collateral class; Or
Comprise each at least a single medicinal material of each apoplexy due to endogenous wind that is selected from the smooth network class of gas, disperse blood stasis and dredge collateral class, the collateral dredging class of eliminating the phlegm and dispelling wind and removing obstruction in the collateral class; Or
Comprise and be selected from flourish each at least a single medicinal material of each apoplexy due to endogenous wind of supporting channels class, the smooth network class of gas, disperse blood stasis and dredge collateral class, the collateral dredging class of eliminating the phlegm and dispelling wind and removing obstruction in the collateral class; Or
Comprise and be selected from flourish each at least a single medicinal material of each apoplexy due to endogenous wind of supporting channels class, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, dispelling wind and removing obstruction in the collateral class, dispelling toxins and dredging collaterals class; Or
Comprise and be selected from flourish each at least a single medicinal material of each apoplexy due to endogenous wind of supporting channels class, the smooth network class of gas, disperse blood stasis and dredge collateral class, resolving mass and removing the obstruction of the collateral class, the collateral dredging class of eliminating the phlegm, dispelling wind and removing obstruction in the collateral class and dispelling toxins and dredging collaterals class.
9. medicine according to Claim 8 is selected from following combination comprising any one:
Comprise Radix Ginseng and Radix Salviae Miltiorrhizae, the weight ratio of the two is 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2; Or
Comprise Scolopendra+Rhizoma Pinelliae+Scorpio, three's weight ratio is 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2; Or
Comprise Scolopendra+Rhizoma Arisaematis+Caulis Spatholobi+Fructus Aurantii Immaturus, four weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2; Or
Comprise Scolopendra+Rhizoma Pinelliae+Hirudo+Radix Ginseng+Ramulus Cinnamomi, five weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2; Or
Comprise the Radix Astragali+Rhizoma Smilacis Glabrae+Radix Angelicae Pubescentis+Rhizoma Chuanxiong+Carapax Trionycis+Rhizoma Arisaematis, six weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2; Or
Comprise Scolopendra+Rhizoma Pinelliae+Hirudo+Radix Ginseng+Ramulus Cinnamomi+Carapax Trionycis+Radix Paeoniae Rubra, wherein seven weight ratio is: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2: 0.1-2, preferred 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5: 0.5-1.5, more preferably 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2: 0.8-1.2.
10. method for preparing according to any described medicine among the claim 4-9, comprise the said effective ingredient that one or more are selected from single medicinal material, Chinese medicine composition and preparation thereof, chemical effective ingredient, Pharmaceutical composition and preparation, biological effective components, Pharmaceutical composition and the preparation thereof is combined with in case of necessity one or more pharmaceutic adjuvants, for example use conventional pharmaceutic adjuvant and/or use conventional formulation method to make it combination.
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