CN104274549A

CN104274549A - Application of traditional Chinese medicine composition to prepare medicines for preventing atherosclerosis

Info

Publication number: CN104274549A
Application number: CN201310274740.XA
Authority: CN
Inventors: 王磊; 王宏涛; 唐思文; 李淳瑞
Original assignee: Hebei Yiling Pharmaceutical Research Institute Co Ltd
Current assignee: Hebei Yiling Pharmaceutical Research Institute Co Ltd
Priority date: 2013-07-03
Filing date: 2013-07-03
Publication date: 2015-01-14

Abstract

The invention discloses application of a traditional Chinese medicine composition to prepare medicines for preventing atherosclerosis, belongs to the field of application of traditional Chinese medicines. The traditional Chinese medicine composition is composed of ginseng, hirudo, scolopendra, scorpio, ground beetle, periostracum cicadae, radix paeoniae rubra, borneol and the like. The traditional Chinese medicine composition is used by combining atorvastatin and aspirin for inhibiting NF-kappaB signal pathway activation. The traditional Chinese medicine composition is small in side effect and good in effect.

Description

A kind of Chinese medicine composition is preparing the application in prevention of arterial anti-atherosclerotic agent

Technical field

The invention belongs to application in TCM field, be specifically related to a kind of novelty teabag of Chinese medicine composition.

Background technology

Atherosclerosis (AS) is the main pathological basis of multiple cardiocerebrovasculaevents events, relates to lipid metabolic disorder, endothelial injury, coagulation disorder etc.Be characterized in ductus arteriosus wall thicken hardening, to follow the string and tube chamber reduces, because the lipid outward appearance gathered on endarterium is yellow medicated porridge sample, be therefore called atherosclerosis.Mainly involve big-and-middle-sized tremulous pulse, its clinical manifestation is mainly based on the symptom of afflicted organ.To primary disease pathogenesis, there is multiple theory to set forth from different perspectives, comprise lipid and infiltrate theory, thrombosis theory, smooth muscle cell clonal theory etc.In recent years most scholar supports " endothelial injury reaction theory ".Think the final all damaged arteries inner membrances of the various Major Risk Factors of primary disease, and the result of the formation of atherosclerotic lesion inflammation-fibroproliferative reaction that to be tremulous pulse make inner film injury.

NF-κ B is present in vascular endothelial cell, smooth muscle cell and macrophage, be key link and the co-channel of the regulatory transcription inflammation factor (as chemotactic factor and adhesion molecule etc.), its activation is a key factor of the initial generation of AS.In NF-κ B Classical pathway, I κ K/I κ B/NF-κ B is the system of organic connections, plays an important role in the transcribing of AS inflammation target gene.Under different stimulating factor effects, different stream signal can cause I κ B(NF-kB inhibitor) protein phosphorylation and degrading, cause NF-κ B to activate, the former then depends on I κ K(I κ B kinases) regulation and control.

Summary of the invention

The object of the invention is to provide a kind of Chinese medicine composition and is preparing the atherosis application of prevention of arterial, particularly combines the application in atorvastatin, aspirin suppression NF-κ B signal path pharmacological activation.

This Chinese medicine composition is made up of the crude drug of following weight portion:

Radix Ginseng 3-10 Hirudo 3-11 Eupolyphaga Seu Steleophaga 5-10 Olibanum (processed) 1-5 Radix Paeoniae Rubra 3-9 Lignum Dalbergiae Odoriferae 1-5 Lignum Santali Albi 1-5 Scorpio 3-9 Periostracum Cicadae 3-12 Scolopendra 1-3 Borneolum Syntheticum 1-7 Semen Ziziphi Spinosae (parched) 3-10.

As optimal way, this Chinese medicine composition is made up of the crude drug of following weight portion:

Radix Ginseng 6 Hirudo 10 Eupolyphaga Seu Steleophaga 7 Olibanum (processed) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferae 2

Lignum Santali Albi 2 Scorpio 7 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosae (parched) 5.

Or:

Radix Ginseng 10 Hirudo 3 Eupolyphaga Seu Steleophaga 10 Olibanum (processed) 5 Radix Paeoniae Rubra 9 Lignum Dalbergiae Odoriferae 5

Lignum Santali Albi 5 Scorpio 9 Periostracum Cicadae 12 Scolopendra 3 Borneolum Syntheticum 1 Semen Ziziphi Spinosae (parched) 10.

Or:

Radix Ginseng 3 Hirudo 11 Eupolyphaga Seu Steleophaga 5 Olibanum (processed) 1 Radix Paeoniae Rubra 3 Lignum Dalbergiae Odoriferae 1

Lignum Santali Albi 1 Scorpio 3 Periostracum Cicadae 3 Scolopendra 1 Borneolum Syntheticum 7 Semen Ziziphi Spinosae (parched) 3.

The active component of Chinese medicine composition is made up of following ingredients:

A mean diameter be less than 100 μm Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga, Periostracum Cicadae and Olibanum (processed) medicated powder;

B Borneolum Syntheticum medicated powder;

The volatile oil that c is extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi;

The alcohol-extracted extract of alcohol extract after d Radix Ginseng ethanol extraction after concentrated;

The water extracted immersing paste that the Aqueous extracts of the Aqueous extracts after the Aqueous extracts of the Lignum Dalbergiae Odoriferae after e extract component c and Lignum Santali Albi medicinal residues, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) decoct with water and the medicine residues of Radix Ginseng after extract component d filters, be condensed into after mixing.

In Chinese medicine composition of the present invention, as the latin name of the crude drug of active component and processing method thereof from " Chinese medicine voluminous dictionary " (in July, 1977, the first edition, Shanghai science tech publishing house) and " Chinese Pharmacopoeia " (version in 2005, Chemical Industry Press).

The preparation formulation of Chinese medicine composition of the present invention is capsule, tablet, granule, powder, oral liquid or pill.

For enabling above-mentioned dosage form realize, the acceptable adjuvant of pharmacy need be added when preparing these dosage forms, such as: filler, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctives, antiseptic, substrate etc.Filler comprises: starch, pregelatinized Starch, lactose, mannitol, chitin, microcrystalline Cellulose, sucrose etc.; Disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc.; Lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.; Suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc.; Binding agent comprises, starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; Sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.; Correctives comprises: sweeting agent and various essence; Antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, acetic acid chloroethene are fixed, Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods; Substrate comprises: PEG6000, PEG4000, insect wax etc.

The capsule that the present invention applies described Chinese medicine composition is made preferably by following preparation method:

A) each crude drug is taken according to weight ratio;

B) pulverizing medicinal materials technique:

By Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and Periostracum Cicadae five kinds of worm medicines after cleaning, washing process and clean the Olibanum (processed) after the process of preparing Chinese medicine and prepare burden by prescription, pulverized by pulverizer, medicated powder fineness reaches more than 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication technique, makes medicated powder mean diameter be less than 100 μm; Medical material to be comminuted, after cleaning, drying sterilizing, is prepared burden;

C) concentrated and drying process is extracted:

Use water extraction again after Lignum Dalbergiae Odoriferae and the first extracting in water volatile oil of Lignum Santali Albi, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) decoct with water, after Aqueous extracts filters, and one-tenth extractum to be concentrated; After Radix Ginseng ethanol extraction, then use water extraction, alcohol extract is condensed into alcohol-extracted extract after reclaiming ethanol, and Aqueous extracts is condensed into the water extracted immersing paste after filtering and mixing with all Aqueous extracts;

D) preparation process:

In Fluidbedgranulatingdrier, add superfine powder flour, then step c) gained extraction extractum is sprayed into granulation; By the granule made through granulate, add Borneolum Syntheticum fine powder, spray into the volatile oil extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, by capsule filler filling after mixing, make capsule.

Or capsule is made up of following steps:

A) each crude drug is taken according to weight ratio;

B) pulverizing medicinal materials technique:

C) concentrated and drying process is extracted:

Use water extraction again after Lignum Dalbergiae Odoriferae and the first extracting in water volatile oil of Lignum Santali Albi, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) decoct with water, after Aqueous extracts filters, and one-tenth extractum to be concentrated; After Radix Ginseng ethanol extraction, then use water extraction, alcohol extract is condensed into alcohol-extracted extract after reclaiming ethanol, and Aqueous extracts is condensed into the water extracted immersing paste after filtering and mixing with all Aqueous extracts, and extractum Direct spraying is dried to spray powder;

D) preparation process:

By superfine powder flour and step c) be added in Fluidbedgranulatingdrier together with gained spray drying powder, then spray solvent and make granule; By the granule made through granulate, add Borneolum Syntheticum fine powder, spray into the volatile oil extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, by capsule filler filling after mixing, make capsule.

In order to verify effect of the present invention, do following experiment

materials and methods

?1 experiment material

1.1 laboratory animal

The male ApoE of SPF level ^-/-mice 140, body weight 20 ~ 22g, is purchased from Peking University's Experimental Animal Center, (strain C57BL/6J, purchased from American Jackson laboratory), credit number: SCXK(capital) 2006-2008.With the male C of genetic background ₅₇bL/6J mice 20, body weight 20 ~ 22g, is purchased from Beijing Vital River Experimental Animals Technology Co., Ltd., credit number: SCXK(capital) 2006-0009.Raise in Hebei Yiling Pharmaceutical Research Institute's pharmacology barrier experiments room, illumination 12 hours/day, temperature 20-23 DEG C, relative humidity 40-60%.

1.2 Experimental agents

1.3 main agents

1.4 equipment and equipment

2 experimental techniques

2.1 modelings, grouping and administration

ApoE ^-/-mice adapt to nursing within 3 days, be divided into model group, ATO(atorvastatin afterwards at random) group, ASP(aspirin) group, the TXL(present composition) group, A+A(atorvastatin associating aspirin) group, the ATS-L(present composition associating atorvastatin, aspirin low dose group) group, ATS-H(ATS high dose group) group, amount to 7 groups (n=20), (heat forms: carbohydrate 20.1% in continuous high fat nursing, fat 59.8%, protein 20.1%).Choose homology C57BL/ 6J mice 20, as Normal group simultaneously.Wherein ATO group is with 6.0mg/kg/d gavage (anthropomorphic quantity 40mg/d); ASP group is with 25mg/kg.d gavage (anthropomorphic quantity 150mg/d); TXL group is with 1.5g/kg.d gavage (anthropomorphic quantity 4.56g crude drug/d); ATO+ASP group adds ASP 25mg/kg/d gavage with ATO 6.0mg/kg.d; ATS-L group adds TXL 1.5g/kg.d with ATO 3.0mg/kg.d and adds ASP 12.5mg/kg.d gavage; ATS-H group adds TXL 1.5g/kg.d with ATO 6.0mg/kg.d and adds ASP 25mg/kg.d gavage.Normal group and model group give isopyknic normal saline, and after 12 weeks, fasting 12h, conventional putting to death is detected.

2.2 Indexs measure and method

2.2.1 the mrna expression of aortic tissue I κ K β, I κ Ba, NF-κ Bp65

Adopt real time fluorescent quantitative reverse transcriptional PCR (RT-PCR) detection method:

Sample reception: experiment end, anesthesia is got blood and is put to death mice, left ventricle perfusion PBS, the iliac artery crotch of the whole aorta of anatomical isolation to ventral aorta is started from aorta initial part, comprise and be separated left side brachiocephalic trunk tremulous pulse and innominate artery three branches, 0.9% normal saline flushing blood stains, carefully peel off adventitial tissue, put into Liquid nitrogen storage rapidly.

RNA extracts: get about 100mg and be organized in ice bathing homogenizer, add 1ml Trizol, grind to form homogenate rapidly, add 200 μ l chloroforms, and concussion 30S, places 5 min on ice.4 DEG C, 12000 rpm, centrifugal 10 min, get upper water phase transfer in another 1.5ml centrifuge tube, add isopyknic isopropyl alcohol, put upside down mixing ,-20 DEG C of standing 2h.Then 4 DEG C, 12000 rpm, centrifugal 20 min, abandon supernatant, add 1ml 75% ethanol, mix gently, 4 DEG C, 12000 rpm, centrifugal 10min, exhaustion supernatant, dries under room temperature, and add the deionized water dissolving precipitation of 20 μ l DEPC process ,-80 DEG C save backup.

The purity of RNA and integrity detection: get RNA solution 4ul, detect through 1% agarose gel electrophoresis, obviously visible 28S, 18S band, and 28S is the twice of 18S band, and 5S band is more weak, and disperse, show that RNA degraded is less, integrity is good.OD is measured respectively with 756 type ultraviolet spectrophotometers ₂₆₀with OD ₂₈₀, OD ₂₆₀/ OD ₂₈₀ratio, between 1.8-2.0, shows that the RNA protein contamination extracted is little, therefore can in follow-up reverse transcription reaction.

Reverse transcription (RT):

42 DEG C of reverse transcription 50min, 95 DEG C of 5min deactivation reverse transcription.

Syber Green fluorescence quantitative PCR detection:

PCR reactant liquor table composed as follows:

PCR thermal circulation parameters: 96 DEG C of 4min, then three-step reactions: 94 DEG C of 30S, 58 DEG C of 30s, 72 DEG C of 30s, carry out 40 circulations, in each circulation the 3rd step namely: 72 DEG C of 30s collect fluorescence signals.

Real-time fluorescence quantitative PCR interpretation of result: after amplification, enters interpretation of result interface, take GAPDH as internal reference gene, compared with matched group, obtains the relative quantification value (RQ value) of destination gene expression, RQ value is used for statistical analysis.

Primer sequence:

2.2.2 the protein expression of aortic tissue I κ K β, I κ Ba, P-I κ Ba and NF-κ Bp65

Adopt Western blot detection method, sample reception: experiment end, left ventricle perfusion PBS, whole piece aorta is carefully peeled off to iliac artery crotch from aorta initial part, comprise left side brachiocephalic trunk tremulous pulse and innominate artery three branches, 0.9% normal saline flushing blood stains, carefully peel off adventitial tissue, put into Liquid nitrogen storage rapidly.

Organize total protein extraction: get and organize about 100mg, add 1ml cell pyrolysis liquid (1 % NP40,150 mmol/L NaCl, 50 mmol/L Tris-HCl, pH7.5,10% glycerol, 1 mmol/L Na ₃vO ₄, 1mmol/L PMSF, 1mmol/L DTT) in, ice bath homogenate, abundant cracking 20 min, 4 DEG C, centrifugal 10 min of 8000 rpm, collect supernatant, carry out protein quantification with Nanodrop2000 spectrophotometer.

Sds polyacrylamide gel electrophoresis: record 12% separation gel and 5% concentrated glue, get equal protein sample and 5 × SDS sample-loading buffer (0.1mmol/ L Tris-HCl, pH 6.8,20% glycerol, 0.1% bromophenol blue, 10% beta-mercaptoethanol, 4%SDS) mix homogeneously, 100 DEG C of boiling water bath heating 5min make albuminous degeneration.After cooling, be splined in 12 % PAGE gel wells with micro sample adding appliance.90 voltage stabilizing electrophoresis are about 30min, enter after separation gel until bromophenol blue, use 120 V voltage stabilizing electrophoresis instead, move to bottom gel, about 2h to bromophenol blue leading edge, take out gel.

Half-dried transferring film: after electrophoresis, half-dried transferring film (transferring film buffer is 48 mmol/L Tris, 39 mmol/L glycine, 1.3 mmol/L SDS, 20% methanol, pH 9.2) is carried out to gel.Half dry type transferring film groove negative electrode upper, anode under.Protein moving direction from top to bottom.Transfer current 50 ~ 250 mA, transfer time 20 ~ 60 min.

Close: transferring film is complete, take out PVDF film, be placed in TTBS (10 mmol/L Tris-HCl, pH 8.0,150 mmol/L NaCl, the 0.05 % Tween-20) confining liquid containing 5 % defatted milk powder, room temperature closes 2 h.

One anti-binding: the pvdf membrane after closing is inserted primary antibodie solution/β-actin(1:1000 that TTBS dilutes (1:500)) diluent, 4 DEG C of slow shaken over night.

Wash film: take out pvdf membrane and put into the plate filling appropriate TTBS, room temperature washes film, each 10 min, totally 3 times.

Two anti-bindings: pvdf membrane is inserted in right amount with in two anti-solution of the horseradish peroxidase-labeled of TTBS 1:10000 dilution, room temperature reaction 2 h.

Chemoluminescence method detects: first wash film 3 times, each 10min by TTBS room temperature, then uses TBS (10 mmol/L Tris-HCl, pH 8.0,150 mmol/L NaCl) to wash film 1 time, about 5 min.Antibodies zone chemoluminescence method detects.

Analyze: by film scanning, under Labworks software, absorbance scoring scan is carried out to band, using β-actin as internal reference, with the relative expression quantity of albumen for the purpose of the ratio of the film gray value/β-actin internal reference film gray value of genes of interest, carry out statistical analysis.

3 statistical procedures

Enumeration data represents with mean ± standard deviation, adopts SPSS13.0 to add up.First test of normality is carried out, meet the data of normal distribution, mean compares with one factor analysis of variance (One-Way ANOVA), compare between two and adopt least significant difference (least significant difference, LSD), with P < 0.05 for there being statistical significance.

result

?the mrna expression of 1 aortic tissue I κ K β, I κ Ba, NF-κ Bp65

Compare with Normal group, the mrna expression of model group mouse aorta I κ K β, NF-κ Bp65 significantly raises (P < 0.01), and I κ B α mrna expression significantly lowers (P < 0.01); Compare with model group, except ATO group I κ K β mrna expression is without except significant change (P > 0.05), other each medication groups all can reduction I κ K β in various degree, NF-κ Bp65 mrna expression, raise I κ B α mrna expression (P<0.05, P<0.01); Compare between each medication group: TXL group I κ K β mrna expression level is starkly lower than ATO group (P<0.05), all the other index mrna expression levels and ATO group, the more equal no significant difference of ASP group (P > 0.05); A+A, ATS-L group I κ K β, NF-κ Bp65 mrna expression level are starkly lower than three prescription group (P<0.05, P<0.01), I κ B α mrna expression aspect all apparently higher than three prescriptions with group (P<0.05, P<0.01); ATS-H group I κ K β, NF-κ Bp65 mrna expression level are starkly lower than A+A and ATS-L group (P<0.01, P<0.05), IKB α mrna expression level is apparently higher than A+A and ATS-L group (P<0.01, P<0.05) (table 1).

The protein expression of 2 aortic tissue I κ K β, I κ B α, p-I κ Ba and NF-κ Bp65

Compare with normal group, the protein expression of model group mouse aorta I κ K β, p-I κ Ba, NF-κ Bp65 significantly raises (P < 0.01), and I κ B α protein expression is significantly lowered (P < 0.01); Compare with model group, except ATO group I κ K β protein expression is without except significant change (P > 0.05), other each medication groups all can reduction I κ K β, p-I κ Ba in various degree, NF-κ Bp65 protein expression, raise I κ B α protein expression (P<0.05, P<0.01); Compare between each medication group: TXL group I κ K β protein expression level is starkly lower than ATO group (P<0.05), all the other protein expression levels and ATO group, the more equal no significant difference of ASP group (P > 0.05); A+A and ATS-L organizes I κ K β, p-I κ Ba, NF-κ Bp65 protein expression level is starkly lower than three prescription group (P<0.05, P<0.01), I κ B α protein expression all apparently higher than three prescriptions with group (P<0.05, P<0.01); ATS-H group I κ K β, p-I κ Ba, NF-κ Bp65 protein expression level are starkly lower than A+A and ATS-L group (P<0.01, P<0.05), IKB α protein expression level is apparently higher than A+A and ATS-L group (P<0.01, P<0.05) (Fig. 1 ~ 5).

Brief summary

Nuclear Factor-Kappa B (nuclear factor-kappaB, NF-κ B), be mainly present in mononuclear cell, blood vessel endothelium and smooth muscle cell, P50/P65 heterodimer is the principal mode of its activity.Research finds, NF-κ B can with the kB site generation specific binding at inflammatory reaction, the necessary cytokine profiles of cell adhesion, the isogenic promoter of adhesion factor or enhancer position, and start and regulate and control transcribing of these genes, in AS pathological process, there is important function.EMSA technology confirms that mankind AS tissue macrophages, endotheliocyte and SMC exist obvious NF-κ B and activate first.Also the activation of NF-κ B can be detected with the coronary artery endothelial cell of pig after high fat feeding.During high fat, oxygen-derived free radicals release obviously strengthens, by oxidoreduction activation NF-κ B, thus start endotheliocyte related cell adhesion molecule (ICAM-1, VCAM-1), monocyte chemoattractant protein (MCP-1), the transcribing and copying of M-CSF (GM-CSF), its protein expression is increased, thus promote that the local of mononuclear cell and endotheliocyte is sticked, moves and broken up, increase the weight of the formation of foam cell, start the generation of AS.And the generation of inflammatory factor and release increase, activate again NF-κ B signal path further, cause initial inflammatory signals constantly to amplify, accelerate AS process.This result of study shows high fat induction ApoE ^-/-in mice AS, mRNA and the protein expression of aorta NF-κ Bp65 obviously raise, mRNA and the protein expression of ATS two dosage group aorta NF-κ Bp65 are obviously significantly lowered, be better than model group and other each medication groups, under pointing out high smectic state, NF-κ B is activated, body inflammatory reaction strengthens, ATS obviously can suppress the activation of NF-κ B after intervening, effect is better than three prescriptions and uses and two Western medicine couplings, may be that ATS strengthens one of reason of antiinflammatory curative effect.

The I κ B α degraded caused in the signal transduction activation I κ K β catalysis I κ B α phosphorylation of NF-κ B Classical pathway middle and upper reaches complexity is key point.I κ B Profilin (inhibitory κ B, I κ B) when cell is in quiescent condition, P50/P65 heterodimer is combined with NF-κ B Profilin (I κ B α) monomer the trimer compositions formed makes NF-κ B be present in endochylema with inactivated state.When signal various after cell irriate activates I kappa b kinase (I κ B kinase, I κ K) complex via different modes, wherein take as the leading factor with the activation of I κ K β ^[9], 32 in the I κ K β phosphorylation I κ B α after activation and 36 serine residues, I κ B α degrades, and itself and p50/p65 are dissociated, thus activates NF-κ B, and transposition is in karyon, starts special target gene and transcribes.Therefore, I κ K β/I κ B α/NF-κ B, as the entirety of organic connections, regulates and controls the series of genes expression that inflammatory reaction, immunoreation etc. are correlated with.Use various means to block arbitrary link in I κ K β/I κ B α/NF-κ B signal path theoretically and all can reach certain therapeutic effect to relevant disease.

The NF-kB activity that statins can suppress many factors to bring out strengthens, and research finds that atorvastatin is by reducing I κ B α phosphorylation and the human vascular endothelial NF-kB activity suppressing lipopolysaccharide to cause of degrading further.It is the competitive inhibitor of I κ K β ATP-binding site that aspirin is also proved to be.Research finds that aspirin can be the activity of dose-dependent inhibition I κ K β, and the phosphorylation of I κ B α and the activation of NF-κ B afterwards.Chinese medicine composition of the present invention is as Chinese medicine compound preparation, have and significantly suppress blood vessel endothelium inflammatory effect, previously research has confirmed that it can directly suppress high fat to damage rabbit aorta NF-κ B nuclear translocation, reduces adhesion factor gene and protein expression, alleviates AS pathology damage.Three kinds of medicines all can act on a certain link in the classical activated channel of NF-κ B, to disturb transcribing of the correlation factor that activated by NF-κ B signal transduction pathway.This result of study is presented at high fat induction ApoE ^-/-in mice AS model, in aortic tissue, the mRNA of I κ K β and protein expression all significantly raise, and mRNA and the protein expression of I κ B α are significantly lowered, and the albumen of p-I κ B α also obviously raises.The mRNA of ATO group I κ K β and protein expression are without significant change, but the mRNA of I κ B α and protein expression are significantly lowered, and the albumen of p-I κ B α obviously raises; MRNA and the protein expression of TXL and ASP group I κ K β are all significantly lowered, and mRNA and the protein expression of I κ B α all significantly raise, and the albumen of p-I κ B α is also obviously lowered.And the mRNA of three prescription group NF-κ Bp65 and protein expression are all significantly lowered; The mRNA of ATS two dosage group I κ K β and NF-κ Bp65 of three medicine couplings and protein expression are lowered more obvious, the mRNA of I κ B α and protein expression raise more remarkable, the protein expression of p-I κ B α is also obviously lowered, and effect is obviously better than three prescriptions and uses and two Western medicine couplings.High fat is pointed out to induce ApoE ^-/-in mice AS process, I κ K β/I κ B α/NF-κ B signal path is activated, cause terminal NF-κ Bp65 increased activity, start inflammatory reaction, the necessary cytokine profiles of cell adhesion, the isogenic transcript and expression of adhesion factor, participate in the formation of AS.AST is by the different links of interference I κ K β/I κ B α/NF-κ B signal path, and the collaborative activation suppressing NF-κ Bp65, plays potentiation antiinflammatory action.

Accompanying drawing explanation

Fig. 1 is each medication group I κ K β, p-I κ Ba, p65 I κ B α protein expression figure;

Fig. 2 be each medication group I κ K β protein ratio comparatively;

Fig. 3 be each medication group p-I κ Ba protein ratio comparatively;

Fig. 4 be each medication group I κ B α protein ratio comparatively;

Fig. 5 be each medication group p65 protein ratio comparatively;

Wherein, 1. normal group, 2. model group, 3. ATO group, 4.ASP; 5.TXL; 6.A+A; 7.ATS-L; 8.ATS-H.

Detailed description of the invention

Embodiment 1:

A) crude drug formula is:

Radix Ginseng 39.6g Hirudo 72.6g Eupolyphaga Seu Steleophaga 46.2g Olibanum (processed) 13.2g Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 19.8g Periostracum Cicadae 46.2g Scolopendra 6.6g Borneolum Syntheticum 33g Semen Ziziphi Spinosae (parched) 33g;

B) pulverizing medicinal materials technique:

By Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and Periostracum Cicadae five kinds of worm medicines after cleaning, washing process and clean the Olibanum (processed) after the process of preparing Chinese medicine and prepare burden by prescription, pulverized by pulverizer, medicated powder fineness reaches more than 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication technique, makes medicated powder mean diameter be less than 30 μm; Medical material to be comminuted, after cleaning, drying sterilizing, is prepared burden;

C) concentrated and drying process is extracted:

Use water extraction again after Lignum Dalbergiae Odoriferae and the first extracting in water volatile oil of Lignum Santali Albi, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) add suitable quantity of water and decoct secondary, each 3 hours, merge Aqueous extracts, after filtration, and one-tenth extractum to be concentrated; Radix Ginseng with appropriate 70% ethanol extraction secondary, each 3 hours, merge extractive liquid, reclaim ethanol extremely without alcohol taste, use water extraction again, it is 1.05 alcohol-extracted extracts that alcohol extract is condensed into 60 DEG C of mensuration relative densities, and Aqueous extracts is concentrated into 60 DEG C after filtering and mixing with above-mentioned all Aqueous extracts and measures the clear paste that relative density is 1.05, for subsequent use;

D) preparation process:

In Fluidbedgranulatingdrier, add superfine powder flour, then step c) gained extraction extractum is sprayed into granulation; By the granule made through granulate, add Borneolum Syntheticum fine powder, spray into the volatile oil extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, by capsule filler filling after mixing, make 1000 capsules.

The consumption of medicine of the present invention is each 2-4 grain, daily three times.

Embodiment 2

A) crude drug formula is:

Radix Ginseng 66g Hirudo 52.8g Eupolyphaga Seu Steleophaga 46.2g Olibanum (processed) 13.2g

Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 59.4g

Periostracum Cicadae 46.2g Scolopendra 6.6g Borneolum Syntheticum 33g Semen Ziziphi Spinosae (parched) 33g

B) pulverizing medicinal materials technique:

By Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and Periostracum Cicadae five kinds of worm medicines after cleaning, washing process and clean the Olibanum (processed) after the process of preparing Chinese medicine and prepare burden by prescription, pulverized by pulverizer, medicated powder fineness reaches more than 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication technique, makes medicated powder mean diameter be less than 70 μm; Medical material to be comminuted, after cleaning, drying sterilizing, is prepared burden;

C) concentrated and drying process is extracted:

Use water extraction again after Lignum Dalbergiae Odoriferae and the first extracting in water volatile oil of Lignum Santali Albi, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) add suitable quantity of water and decoct secondary, each 3 hours, merge Aqueous extracts, after filtration, and one-tenth extractum to be concentrated; Radix Ginseng with appropriate 70% ethanol extraction secondary, each 3 hours, merge extractive liquid, reclaim ethanol extremely without alcohol taste, use water extraction again, alcohol extract is condensed into relative density and is determined as 1.0 alcohol-extracted extracts at 60 DEG C, and Aqueous extracts is concentrated into 60 DEG C after filtering and mixing with above-mentioned all Aqueous extracts and measures the clear paste that relative density is 1.0, for subsequent use;

D) preparation process:

Superfine powder flour is added, then by step c in Fluidbedgranulatingdrier) gained extracts extractum and sprays into granulation; By the granule made through granulate, add Borneolum Syntheticum fine powder, spray into the volatile oil extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, preparation process is pressed into 1000 routinely.

The consumption of medicine of the present invention is each 2-4 sheet, daily three times.

Embodiment 3: the preparation of pill

A) crude drug formula is:

Radix Ginseng 39.6g Hirudo 66g Eupolyphaga Seu Steleophaga 46.2g Olibanum (processed) 13.2g

Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 46.2g

B) pulverizing medicinal materials technique:

By Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and Periostracum Cicadae five kinds of worm medicines after cleaning, washing process and clean the Olibanum (processed) after the process of preparing Chinese medicine and prepare burden by prescription, pulverized by pulverizer, medicated powder fineness reaches more than 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication technique, makes medicated powder mean diameter 10 μm; Medical material to be comminuted, after cleaning, drying sterilizing, is prepared burden;

C) concentrated and drying process is extracted:

Use water extraction again after Lignum Dalbergiae Odoriferae and the first extracting in water volatile oil of Lignum Santali Albi, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) add suitable quantity of water and decoct secondary, each 3 hours, merge Aqueous extracts, after filtration, and one-tenth extractum to be concentrated; Radix Ginseng with appropriate 70% ethanol extraction secondary, each 3 hours, merge extractive liquid, reclaim ethanol extremely without alcohol taste, use water extraction again, it is 1.0 alcohol-extracted extracts that alcohol extract is condensed into 60 DEG C of mensuration relative densities, and Aqueous extracts is concentrated into 60 DEG C after filtering and mixing with above-mentioned all Aqueous extracts and measures the clear paste that relative density is 1.1, for subsequent use;

D) preparation process:

Preparation process routinely, makes 1000 pills.

Embodiment 4

A) crude drug formula

Radix Ginseng 30g Hirudo 110 g Eupolyphaga Seu Steleophaga 50 g Olibanum (processed) 10 g Radix Paeoniae Rubra 30 g Lignum Dalbergiae Odoriferae 10 g Lignum Santali Albi 10 g Scorpio 30 g Periostracum Cicadae 30g Scolopendra 10g Borneolum Syntheticum 70g Semen Ziziphi Spinosae (parched) 30g;

B) pulverizing medicinal materials technique:

By Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and Periostracum Cicadae five kinds of worm medicines after cleaning, washing process and clean the Olibanum (processed) after the process of preparing Chinese medicine and prepare burden by prescription, pulverized by pulverizer, medicated powder fineness reaches more than 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication technique, makes medicated powder mean diameter 20 μm; Medical material to be comminuted, after cleaning, drying sterilizing, is prepared burden;

C) concentrated and drying process is extracted:

Use water extraction again after Lignum Dalbergiae Odoriferae and the first extracting in water volatile oil of Lignum Santali Albi, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) add suitable quantity of water and decoct secondary, each 3 hours, merge Aqueous extracts, after filtration, and one-tenth extractum to be concentrated; Radix Ginseng with appropriate 70% ethanol extraction secondary, each 3 hours, merge extractive liquid, reclaim ethanol extremely without alcohol taste, use water extraction again, it is 1.1 alcohol-extracted extracts that alcohol extract is condensed into 60 DEG C of mensuration relative densities, and Aqueous extracts is concentrated into 60 DEG C after filtering and mixing with above-mentioned all Aqueous extracts and measures the clear paste that relative density is 1.1, for subsequent use;

D) preparation process:

Preparation process routinely, makes granule.

Embodiment 5

A) crude drug formula

Radix Ginseng 100g Hirudo 30 g Eupolyphaga Seu Steleophaga 100 g Olibanum (processed) 50 g Radix Paeoniae Rubra 90 g Lignum Dalbergiae Odoriferae 50 g Lignum Santali Albi 50 g Scorpio 90 g Periostracum Cicadae 120 g Scolopendra 30 g Borneolum Syntheticum 10 g Semen Ziziphi Spinosae (parched) 100 g;

B) pulverizing medicinal materials technique:

By Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and Periostracum Cicadae five kinds of worm medicines after cleaning, washing process and clean the Olibanum (processed) after the process of preparing Chinese medicine and prepare burden by prescription, pulverized by pulverizer, medicated powder fineness reaches more than 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication technique, makes medicated powder mean diameter 50 μm; Medical material to be comminuted, after cleaning, drying sterilizing, is prepared burden;

C) concentrated and drying process is extracted:

Use water extraction again after Lignum Dalbergiae Odoriferae and the first extracting in water volatile oil of Lignum Santali Albi, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) add suitable quantity of water and decoct secondary, each 3 hours, merge Aqueous extracts, after filtration, and one-tenth extractum to be concentrated; Radix Ginseng with appropriate 70% ethanol extraction secondary, each 3 hours, merge extractive liquid, reclaim ethanol extremely without alcohol taste, use water extraction again, it is 1.0 alcohol-extracted extracts that alcohol extract is condensed into 60 DEG C of mensuration relative densities, and Aqueous extracts is concentrated into 60 DEG C after filtering and mixing with above-mentioned all Aqueous extracts and measures the clear paste that relative density is 1.0, for subsequent use;

D) preparation process:

Preparation process routinely, makes powder.

Embodiment 6

A) crude drug formula

Radix Ginseng 60g Hirudo 110 g Eupolyphaga Seu Steleophaga 100 g Olibanum (processed) 20 g Radix Paeoniae Rubra 50 g Lignum Dalbergiae Odoriferae 20 g Lignum Santali Albi 20 g Scorpio 73g Periostracum Cicadae 70 g Scolopendra 10 g Borneolum Syntheticum 50 g Semen Ziziphi Spinosae (parched) 50 g;

B) pulverizing medicinal materials technique:

By Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and Periostracum Cicadae five kinds of worm medicines after cleaning, washing process and clean the Olibanum (processed) after the process of preparing Chinese medicine and prepare burden by prescription, pulverized by pulverizer, medicated powder fineness reaches more than 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication technique, makes medicated powder mean diameter 60 μm; Medical material to be comminuted, after cleaning, drying sterilizing, is prepared burden;

C) concentrated and drying process is extracted:

D) preparation process:

Preparation process routinely, makes oral liquid.

Embodiment 7

Crude drug formula is: Radix Ginseng 30g Hirudo 30g Eupolyphaga Seu Steleophaga 50g Olibanum (processed) 10g Radix Paeoniae Rubra 30g Lignum Dalbergiae Odoriferae 10g Lignum Santali Albi 10g Scorpio 30g Periostracum Cicadae 30g Scolopendra 10g Borneolum Syntheticum 10g Semen Ziziphi Spinosae (parched) 30g.Other preparation process are with embodiment 1.

Embodiment 8

Crude drug formula is: Radix Ginseng 100g Hirudo 30g Eupolyphaga Seu Steleophaga 70g Olibanum (processed) 50g Radix Paeoniae Rubra 90g Lignum Dalbergiae Odoriferae 50g Lignum Santali Albi 50g Scorpio 90g Periostracum Cicadae 120g Scolopendra 30g Borneolum Syntheticum 70g Semen Ziziphi Spinosae (parched) 100g.Other preparation process are with embodiment 2.

Claims

1. a Chinese medicine composition is preparing the application in prevention of arterial anti-atherosclerotic agent, this Chinese medicine composition is made up of the crude drug of following weight portion: Radix Ginseng 3-10 Hirudo 3-11 Eupolyphaga Seu Steleophaga 5-10 Olibanum (processed) 1-5 Radix Paeoniae Rubra 3-9 Lignum Dalbergiae Odoriferae 1-5 Lignum Santali Albi 1-5 Scorpio 3-9 Periostracum Cicadae 3-12 Scolopendra 1-3 Borneolum Syntheticum 1-7 Semen Ziziphi Spinosae (parched) 3-10, it is characterized in that the application of this Chinese medicine composition in preparation associating atorvastatin, aspirin suppression NF-κ B signal path pharmacological activation.

2. application according to claim 1, is characterized in that, this Chinese medicine composition is made up of the crude drug of following weight portion:

3. application according to claim 1, is characterized in that, this Chinese medicine composition is made up of the crude drug of following weight portion:

4. application according to claim 1, is characterized in that, this Chinese medicine composition is made up of the crude drug of following weight portion:

5. the application according to any one of claim 1-4, is characterized in that, the active component of described Chinese medicine composition is made up of following ingredients:

B Borneolum Syntheticum medicated powder;

6. the application according to any one of claim 1-4, is characterized in that, the preparation formulation of this Chinese medicine composition is capsule, tablet, granule, powder, oral liquid or pill.

7. application according to claim 6, is characterized in that, described capsule is made up of following steps:

A) each crude drug is taken according to weight ratio;

B) pulverizing medicinal materials technique:

C) concentrated and drying process is extracted:

D) preparation process:

8. application according to claim 6, is characterized in that, described capsule is made up of following steps:

A) each crude drug is taken according to weight ratio;

B) pulverizing medicinal materials technique:

C) concentrated and drying process is extracted:

D) preparation process: