CN109224038B - Traditional Chinese medicine composition containing channel-inducing medicine evodia rutaecarpa for treating blood stasis collateral blocking type hepatic fibrosis and preparation method and application thereof - Google Patents
Traditional Chinese medicine composition containing channel-inducing medicine evodia rutaecarpa for treating blood stasis collateral blocking type hepatic fibrosis and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine composition containing a channel-inducing medicine evodia for treating blood stasis collateral blocking type hepatic fibrosis, a preparation method and application thereof, wherein the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 6-15 parts of fructus evodiae, 15-45 parts of salvia miltiorrhiza, 10-30 parts of curcuma zedoary, 10-20 parts of turmeric, 15-30 parts of citron, 10-20 parts of rheum officinale, 15-40 parts of serissa serissoides, 10-25 parts of hawthorn and 10-20 parts of cupressa glauca. The traditional Chinese medicine composition disclosed by the invention is wide in raw material source, low in price and small in side effect, can improve the liver function of a blood stasis collateral blocking type hepatic fibrosis rat, reduce the hepatic fibrosis marker content and blood viscosity in blood, improve the liver histopathology, has a remarkable curative effect on the blood stasis collateral blocking type hepatic fibrosis, and is a great innovation for treating the blood stasis collateral blocking type hepatic fibrosis.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a traditional Chinese medicine composition containing a channel-inducing medicine evodia rutaecarpa for treating blood stasis collateral blocking type hepatic fibrosis, and a preparation method and application thereof.
Background
Hepatic Fibrosis (HF) is a pathological state caused by acute and chronic liver injury caused by various factors (such as hepatitis virus, alcohol, drugs, parasites and the like) in a repair process, and is characterized in that a large amount of abnormal hyperplasia and precipitation of fibrous tissues in a junction area and liver lobules cause structural deformation of a liver, thereby causing or further aggravating damage to the function of the liver. 25-40% of the liver fibrosis can be developed into cirrhosis, and the liver fibrosis is the early stage of cirrhosis. The data show that global liver cirrhosis lethality increases year by year, from approximately 67 million in 1980 to 100 million in 2010 (Mokdad AA, Lopez AD, Shahraz S, et al. liver cirrhosis mortalities in 187countries between 1980and 2010: a systematic analysis. BMC Med,2014,12: 145.). The liver diseases of China are the most heavily burdened in the world, and according to incomplete statistics, patients with chronic viral hepatitis reach tens of millions, wherein about 10 percent of patients with chronic hepatitis are likely to develop liver fibrosis, and other liver diseases such as autoimmune hepatitis, alcoholic liver disease, non-alcoholic fatty liver, cholestasis and the like can also cause liver fibrosis. Therefore, effective drug treatment is performed in the hepatic fibrosis stage, which is very important for restraining the progress of the disease to the liver cirrhosis.
There is no name of liver fibrosis and description of etiology and pathogenesis of liver fibrosis in traditional Chinese medicine. Clinically, the symptoms of liver fibrosis are various, and according to the clinical manifestations, liver fibrosis can be classified into the categories of diseases such as "liver being", "hypochondriac pain", "jaundice", "accumulation", etc., and the causes of the diseases are related to the affection of damp-heat and epidemic toxin, diet and irregularity, excessive drinking, emotional factors, excessive lying and movement, obesity, etc. Common traditional Chinese medicine symptoms of hepatic fibrosis include liver-qi stagnation, liver-kidney yin deficiency, spleen-kidney yang deficiency, blood stasis blocking collaterals, damp-heat aquatic weeds stagnation and water-dampness blocking 6 types. Although the syndromes have common clinical manifestations, such as hepatosplenomegaly, wiry pulse, and elevated serological indexes, each syndrome has its own special symptoms, and may be associated with certain elevated serological indexes. The research on the correlation between serological indexes and liver fibrosis syndrome indicates that the rise of serum fibrosis indexes is closely related to the traditional Chinese medicine syndrome, wherein the rise of blood stasis collateral blocking serum liver fibrosis indexes is most obvious and is obviously higher than other syndrome types (Majiahong, Jiaya Long, Fang Korea, and the like). the correlation research on the differentiation type of chronic hepatitis B liver fibrosis and the correlation between liver fibrosis pathology and serological indexes is carried out.A liver disease magazine, 2012 and 22(4): 205-.
At present, the treatment aiming at the hepatic fibrosis is limited to control the etiology, and an ideal treatment medicine is lacked. Research shows that many drugs have good anti-fibrosis function in vitro experiments, but have poor in vivo curative effect because most therapeutic drugs cannot form high accumulation in liver and cannot reach effective therapeutic concentration (Van Qian, Lechen, Joe Jian, and the like. research on drug delivery system for treating liver fibrosis is advanced. Chinese university of pharmacy, 2018, 49(3): 263-271.).
The theory of traditional Chinese medicine considers that in the formula compatibility, the action of the channel-guiding drugs is emphasized or concentrated on specific parts to guide the drugs to reach the meridians and viscera directly, thereby improving the curative effect. The channel-inducing medicine is a carrier of the targeted curative effect of the traditional Chinese medicine, has high similarity with the targeted drug delivery in the modern medicine, can make the efficacy of the medicine directly reach the focus if the channel-inducing medicine is used properly, and obviously improves the curative effect.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a traditional Chinese medicine composition containing a channel-inducing medicine evodia fruit for treating blood stasis and collateral obstruction type hepatic fibrosis and a preparation method and application thereof.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a traditional Chinese medicine composition containing a channel-inducing medicine fructus evodiae for treating blood stasis collateral blocking type hepatic fibrosis comprises the following raw material medicines in parts by weight: 6-15 parts of fructus evodiae, 15-45 parts of salvia miltiorrhiza, 10-30 parts of curcuma zedoary, 10-20 parts of turmeric, 15-30 parts of citron, 10-20 parts of rheum officinale, 15-40 parts of serissa serissoides, 10-25 parts of hawthorn and 10-20 parts of cupressa glauca.
Preferably, the traditional Chinese medicine composition containing the channel-inducing medicine evodia for treating blood stasis collateral blocking type hepatic fibrosis comprises the following raw material medicines in parts by weight: 9 parts of fructus evodiae, 30 parts of salvia miltiorrhiza, 20 parts of curcuma zedoary, 15 parts of turmeric, 20 parts of citron, 15 parts of rheum officinale, 30 parts of serissa serissoide, 18 parts of hawthorn and 15 parts of prunus mume.
The weight parts in the present invention may be those known in the medical field such as μ g, mg, g or kg.
The evodia rutaecarpa in the technical scheme of the invention is dry nearly mature fruit of rutaecarpa, Euodia rutaecarpa (Juss.) Benth, var. officinalis (Dode) Huang or evodia rutaecarpa (Juss.) Benth.
The Salvia miltiorrhiza in the technical scheme of the invention is dried roots and rhizomes of Salvia miltiorrhiza bge.
The Curcuma zedoary in the technical scheme of the invention is dried rhizome of Curcuma zedoaria Phaeocaulis Val, Curcuma kwangensis S.G.Lee et C.F.Liang or Curcuma wenyujin Y.H.Chen et C.Ling of Zingiberaceae.
The turmeric in the technical scheme of the invention is dried rhizome of Curcuma longa L.
The citron is the dried mature fruit of the rutaceae Citrus citri Citrus medica L or Citrus wilsoni Tanaka.
The rhubarb in the technical scheme of the invention is the dried root and rhizome of Rheum palmatum L, Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. of Asclepiadaceae.
The Serissa in the technical scheme of the invention is dry whole herb of Serissa japonica (Thunb.) Thunb. or serissoides (DC.) Druce of Serissa in Rubiaceae.
The hawthorn in the technical scheme of the invention is dried mature fruit of Crataegus pinmatifolia Bge, var, major N.E.Br. or Crataegus pincatifida Bgc.
The flos mume is dried flower bud of Prunus mume Sieb. et Zucc. of Rosaceae.
The raw materials for preparing the traditional Chinese medicine composition are monarch drugs, wherein the salvia miltiorrhiza is bitter and cold, the blood circulation is promoted, the stasis is removed, the carbuncle is cured, the zedoary breaks the blood and promotes the circulation of qi, the rhubarb can remove the blood stasis and the heat stasis, and the blood circulation is promoted, the stasis is removed and the pain is relieved; the turmeric has the functions of both blood and qi, warming and dispersing and removing stagnation, the citron has the functions of soothing liver and regulating qi, and the prunus mume has the functions of soothing liver and harmonizing stomach, and the three are ministerial drugs; the hawthorn, as an adjuvant drug, can eliminate turbid pathogen and reduce lipid, the serissa serissoide can promote diuresis and activate collaterals, and the hawthorn, the salvia miltiorrhiza, the zedoary and the rhubarb can enhance the functions of activating blood and dissipating blood stasis when being matched with the salvia miltiorrhiza, the zedoary and the rhubarb; evodia rutaecarpa, fructus evodiae, which mainly enters liver meridian, not only disperses cold pathogen of liver meridian but also disperses depression of liver qi, is a channel-inducing drug of liver meridian and can directly reach the disease site, so it is a guiding drug. The medicines are combined to play the roles of promoting blood circulation, removing blood stasis, soothing the liver and dredging collaterals.
The traditional Chinese medicine composition containing the channel-inducing medicine evodia rutaecarpa is preferably an oral preparation, including decoction, oral liquid, granules, tablets, capsules, pills or granules and the like, and the dosage forms can be prepared by the conventional method in the field.
More preferably, the traditional Chinese medicine composition containing the channel-inducing medicine evodia is decocted with water, and the preparation method comprises the following steps: mixing the raw materials, adding water with the weight 4-8 times that of the mixed raw materials, soaking for 1.5-3 hours, decocting for 15-45 minutes, and filtering; adding water with the weight 5-10 times that of the filter residue into the filter residue, decocting for 30-60 minutes, and filtering; mixing the filtrates, and making into decoction.
More preferably, the traditional Chinese medicine composition containing the channel-inducing medicine evodia rutaecarpa adopts granules, and the preparation method comprises the following steps:
1) mixing and crushing evodia rutaecarpa, curcuma zedoary, curcuma longa, citron, prunus mume and serissa serissoide into coarse powder, adding 50-80% (v/v) ethanol which is 6-10 times of the weight of the coarse powder, soaking for 1-3 hours, then carrying out reflux extraction for 2-3 times, 1-2 hours each time, combining extracting solutions, recovering ethanol, concentrating the extracting solution, carrying out vacuum drying to obtain an extract, crushing the extract into fine powder, and sieving the fine powder with a 80-mesh sieve;
2) mixing the salvia miltiorrhiza, the rheum officinale and the hawthorn, adding water according to a material-liquid ratio of 1:10, soaking for 1-2 hours, performing reflux extraction, concentrating an extracting solution, drying to obtain an extract, crushing the extract into fine powder, and sieving by using a 80-mesh sieve;
3) mixing the sieved extract powder obtained in the steps 1) and 2), adding 1.0-1.5 times of microcrystalline cellulose, 0.5-0.9 times of lactose and 1.5-2.0 times of polyvinylpyrrolidone K30 aqueous solution with the mass fraction of 5% by weight of the mixed powder, uniformly mixing, granulating, drying, grading and bagging to obtain the finished product.
More preferably, the traditional Chinese medicine composition containing the channel-inducing medicine evodia is a tablet, and the preparation method comprises the following steps:
1) mixing and crushing evodia rutaecarpa, curcuma zedoary, curcuma longa, citron, prunus mume and serissa serissoide into coarse powder, adding 50-80% (v/v) ethanol which is 6-10 times of the weight of the coarse powder, soaking for 1-3 hours, then carrying out reflux extraction for 2-3 times, 1-2 hours each time, combining extracting solutions, recovering ethanol, concentrating the extracting solution, carrying out vacuum drying to obtain an extract, crushing the extract into fine powder, and sieving the fine powder with a 80-mesh sieve;
2) mixing the salvia miltiorrhiza, the rheum officinale and the hawthorn, adding water according to a material-liquid ratio of 1:10, soaking for 1-2 hours, performing reflux extraction, concentrating an extracting solution, drying to obtain an extract, crushing the extract into fine powder, and sieving by using a 80-mesh sieve;
3) mixing the sieved extract powder obtained in the step 1) and the step 2), adding 1.0-1.5 times of microcrystalline cellulose, 0.5-0.9 times of lactose, 1.5-2.0 times of polyvinylpyrrolidone K30 aqueous solution with the mass fraction of 5% and 0.03-0.07 times of talcum powder, uniformly mixing, granulating and tabletting to obtain the finished product.
The invention also provides application of the traditional Chinese medicine composition in preparing a medicine for treating blood stasis collateral blocking type hepatic fibrosis.
The blood stasis collateral blocking type hepatic fibrosis in the technical scheme of the invention means that the disease not only meets the hepatic fibrosis diagnosis standard of western medicine, but also meets the differentiation standard of blood stasis collateral blocking of traditional Chinese medicine.
The inventor of the invention discovers through research that the composition of the red sage root, the zedoary, the turmeric and the rhubarb has a certain treatment effect on blood stasis and collateral obstruction type hepatic fibrosis, the citron, the serissa serissoide, the hawthorn and the prunus mume have a certain improvement effect on blood stasis and collateral obstruction type hepatic fibrosis, but the effect is not obvious, when the composition is used in combination with the composition of the red sage root, the zedoary, the turmeric and the rhubarb, the composition has a better synergistic effect, and the evodia rutaecarpa has a lack of curative effect on blood stasis and collateral obstruction type hepatic fibrosis, but has a remarkable synergistic effect on the composition when the composition is used in combination with the composition. The traditional Chinese medicine composition containing the channel-inducing medicine evodia rutaecarpa provided by the invention has a particularly good effect on treating blood stasis collateral blocking type hepatic fibrosis, and is small in side effect and low in price.
Drawings
FIG. 1 shows the HE staining results of rat liver tissues under a microscope, wherein the HE staining results comprise a normal control group A, a model control group B, a comparative drug 1 group C, a comparative drug 2 group D, a comparative drug 3 group E, a comparative drug 4 group F and a group G of the invention.
FIG. 2 shows the results of Masson staining of rat liver tissues under a microscope, wherein the group A comprises a normal control group, a model B control group, a C contrast drug 1 group, a D contrast drug 2 group, an E contrast drug 3 group, an F contrast drug 4 group and a G invention group.
Detailed Description
The following examples further illustrate the embodiments of the present invention in detail.
EXAMPLE 1 oral liquid preparation (Water decoction) and preparation thereof
1. Weighing the following raw material medicaments according to the prescription amount
2. Preparation method
Mixing the raw materials according to the prescription amount, adding water with the weight 4 times that of the mixed raw materials, soaking for 2 hours, decocting for 20 minutes, and filtering; adding water 6 times the weight of the filter residue into the filter residue, decocting for 40 minutes, and filtering; mixing the two filtrates to obtain decoction.
EXAMPLE 2 oral liquid preparation (Water decoction) and preparation thereof
1. Weighing the following raw material medicaments according to the prescription amount
2. Preparation method
Mixing the raw materials according to the prescription amount, adding water with the weight 4 times that of the mixed raw materials, soaking for 2 hours, decocting for 20 minutes, and filtering; adding water 6 times the weight of the filter residue into the filter residue, decocting for 40 minutes, and filtering; mixing the two filtrates to obtain decoction.
Example 3 oral solid preparation (granule) and preparation thereof
1. Weighing the following raw material medicaments according to the prescription amount
2. Preparation method
1) Mixing fructus evodiae, Curcumae rhizoma, Curcuma rhizome, fructus Citri, flos Pruni mume and herba Serissae Japonicae, pulverizing into coarse powder, adding 70% (v/v) ethanol 8 times of the coarse powder, soaking for 2 hr, reflux-extracting for 3 times (1.5 hr each time), mixing extractive solutions, recovering ethanol, concentrating the extractive solution, vacuum drying to obtain extract, pulverizing into fine powder, and sieving with 80 mesh sieve.
2) Mixing Saviae Miltiorrhizae radix, radix et rhizoma Rhei, and fructus crataegi, adding water according to a material-to-liquid ratio of 1:10, soaking for 1.5 hr, reflux extracting, concentrating the extractive solution, drying to obtain extract, pulverizing the extract into fine powder, and sieving with 80 mesh sieve.
3) Mixing the sieved extract powders obtained in the steps 1) and 2), adding 1.2 times of microcrystalline cellulose, 0.7 times of lactose and 1.8 times of polyvinylpyrrolidone K30 aqueous solution with mass fraction of 5% by weight of the mixed powder, uniformly mixing, granulating, drying, grading and bagging to obtain the finished product.
Example 4 oral solid preparation (tablet) and preparation thereof
1. Weighing the following raw material medicaments according to the prescription amount
2. Preparation method
1) Mixing fructus evodiae, Curcumae rhizoma, Curcuma rhizome, fructus Citri, flos Pruni mume and herba Serissae Japonicae, pulverizing into coarse powder, adding 70% (v/v) ethanol 8 times of the coarse powder, soaking for 2 hr, reflux-extracting for 3 times (1.5 hr each time), mixing extractive solutions, recovering ethanol, concentrating the extractive solution, vacuum drying to obtain extract, pulverizing into fine powder, and sieving with 80 mesh sieve.
2) Mixing Saviae Miltiorrhizae radix, radix et rhizoma Rhei, and fructus crataegi, adding water according to a material-to-liquid ratio of 1:10, soaking for 1.5 hr, reflux extracting, concentrating the extractive solution, drying to obtain extract, pulverizing the extract into fine powder, and sieving with 80 mesh sieve.
3) Mixing the sieved extract powder obtained in the steps 1) and 2), adding 1.2 times of microcrystalline cellulose, 0.7 times of lactose, 1.8 times of polyvinylpyrrolidone K30 aqueous solution with the mass fraction of 5% and 0.05 times of talcum powder, uniformly mixing, granulating and tabletting to obtain the finished product.
Example 5 Effect of a Chinese medicinal composition comprising Evodia rutaecarpa as a channel-inducing agent on blood stasis collateral blocking type hepatic fibrosis
1. Experimental and comparative drugs:
in this experiment, the decoction obtained in example 1 (heated in a water bath and concentrated to 1.80g/ml of crude drug) was used as the experimental drug, and the following comparative drugs were prepared:
comparative drug 1: mixing 3000g of salvia miltiorrhiza, 1500g of rheum officinale, 2000g of curcuma zedoary and 1500g of curcuma longa, adding water with the weight 4 times that of the mixed raw materials, soaking for 2 hours, decocting for 20 minutes, and filtering; adding water 6 times the weight of the filter residue into the filter residue, decocting for 40 minutes, and filtering; mixing the two filtrates to obtain decoction, heating in water bath, and concentrating to obtain extract containing crude drug 0.84 g/ml.
Comparative drug 2: mixing 2000g of citron, 3000g of serissa serissoide, 1800g of hawthorn and 1500g of flos Pruni mume, adding water with the weight 4 times that of the mixed raw materials, soaking for 2 hours, decocting for 20 minutes, and filtering; adding water 6 times the weight of the filter residue into the filter residue, decocting for 40 minutes, and filtering; mixing the two filtrates to obtain decoction, heating in water bath, and concentrating to obtain extract containing crude drug 0.87 g/ml.
Comparative drug 3: mixing Saviae Miltiorrhizae radix 3000g, radix et rhizoma Rhei 1500g, Curcumae rhizoma 2000g, Curcuma rhizome 1500g, fructus Citri 2000g, Serissa japonica 3000g, fructus crataegi 1800g, and flos Pruni mume 1500g, adding water 4 times the weight of the mixed raw materials, soaking for 2 hr, decocting for 20 min, and filtering; adding water 6 times the weight of the filter residue into the filter residue, decocting for 40 minutes, and filtering; mixing the two filtrates to obtain decoction, heating in water bath, and concentrating to obtain extract containing crude drug 1.71 g/ml.
Comparative drug 4: taking 900g of fructus evodiae, adding 4 times of water by weight, soaking for 2 hours, decocting for 20 minutes, and filtering; adding water 6 times the weight of the filter residue into the filter residue, decocting for 40 minutes, and filtering; mixing the two filtrates to obtain decoction, heating in water bath, and concentrating to obtain extract containing crude drug 0.09 g/ml.
2. Method of producing a composite material
2.1 establishment and grouping administration of blood stasis collateral blocking type hepatic fibrosis model
Male SPF grade SD rats 70 were randomly divided into 7 groups of 10 rats by body weight. Normal control group: distilled water for intragastric perfusion without molding; model control group: after the model is made, distilled water is supplied to the stomach; 4 control groups of comparative drugs: respectively gavage and administering contrast drugs 1-4 after molding; the invention group: after the molding, the decoction obtained in example 1 was administered by gavage (heated in water bath and concentrated to 1.80g/ml crude drug content); the experimental drug and the comparative drug are both administered at the 3 rd week of the model, 1 time a day, 10ml/kg of the corresponding drug each time, and 8 weeks continuously.
The method for establishing the blood stasis collateral blocking type hepatic fibrosis model comprises the following steps: the rats except the normal control group are injected with 2ml/kg of the mass fraction of 0.5 percent of the dimethyl nitrosamine into the abdominal cavity for 3 consecutive days from 1 week, 2 days and 3 weeks from the 1 st week, 1 time per day for 4 weeks, and are injected with 0.1mg/kg of norepinephrine into the tail vein from the 2 nd week, 1 time per day, and the molding is finished from the 4 th week; meanwhile, Bovine Serum Albumin (BSA) is injected into tail vein of 0.125g/kg body weight on day 1 and day 10 of the molding process. The normal group rats were injected with physiological saline at the corresponding time points.
2.2 liver function and hepatic fibrosis marker assays
24h after the last administration, the rats were anesthetized and then blood was taken from the abdominal aorta, serum was isolated, and the activities of alanine Aminotransferase (ALT), aspartate Aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were measured, and the contents of Laminin (LN), Hyaluronic Acid (HA) and procollagen type III (PCIII), which are markers of hepatic fibrosis, in the serum were measured by ELISA method to observe the effects on liver function and fibrosis.
2.3 hemorheology testing
3ml of blood was quickly injected into an anticoagulation tube, and the whole blood viscosity (low, medium, high cut) was measured with a ZL9000 automatic hemorheology tester (Beijing Zhonghuangwei science and technology development Co., Ltd.). Another part of the blood sample is stood for 30min, centrifuged for 30min, and the upper plasma is separated to measure the plasma viscosity so as to observe the effect on the blood rheology of rats.
2.4 histopathological Observation of the liver
The liver tissue is fixed by formaldehyde, embedded by conventional paraffin, sliced and stained by conventional HE, and the pathological form of the liver tissue is observed under a microscope so as to observe the treatment effect of the traditional Chinese medicine composition on the blood stasis collateral blocking type hepatic fibrosis.
3. Results
3.1 Effect on liver function
In hepatic fibrosis, the structure of hepatic cell membrane is destroyed, ALT, AST, ALP and the like in hepatic cells leak into blood, so the activity of ALT, AST and ALP in blood serum reflects the degree of impaired liver function to a certain extent. In the present invention, blood of each group of animals 24 hours after the last administration was collected, and ALT, AST, ALP activities in serum were measured to evaluate liver functions of rats. The results are shown in Table 1.
TABLE 1 Effect on liver function in rats
Note: p compared to model control group<0.05，**P<0.01; compared with the group of the comparative drug 3,△P<0.05，△△P<0.01。
as can be seen from Table 1, for liver function of blood stasis collateral obstruction type hepatic fibrosis rat, the combination of Salvia miltiorrhiza, Curcumae rhizoma, Curcuma rhizome, and radix et rhizoma Rhei (comparative drug 1) and the combination of citron, Serissa serissoides, fructus crataegi, and flos Pruni mume (comparative drug 2) have certain improvement effect, and when the two are combined (comparative drug 3), the improvement effect on liver function is obviously improved. Although fructus evodiae has no curative effect on liver function of rats with blood stasis collateral blocking type hepatic fibrosis, when the fructus evodiae is used in combination with the composition (the invention), the fructus evodiae has remarkable synergistic effect on the composition (compared with a comparative medicament 3, P is less than 0.01).
3.2 Effect on hepatic fibrosis markers
HA is an important component of extracellular matrix, and can be increased when other indexes of hepatic fibrosis are not abnormal in early stage, and the content of HA is positively correlated with the degree of hepatic fibrosis. When hepatic fibrosis occurs, LN in the antrum is obviously deposited and released into the blood, so that the LN content in the serum is increased. PC III is cleaved by N-terminal enzyme and enters peripheral blood, and increases with the activity of liver fiber synthesis. The contents of HA, LN and PC III in serum are highly related to the degree of hepatic fibrosis, and are sensitive markers reflecting hepatic fibrosis. The invention detects the contents of HA, LN and PC III in the serum of rats after administration, and the result is shown in Table 2.
TABLE 2 Effect on rat liver fibrosis markers
Note: p compared to model control group<0.05，**P<0.01; compared with the group of the comparative drug 3,△P<0.05，△△P<0.01。
as shown in Table 2, the combination of Danshen root, zedoary, turmeric and rhubarb (comparative drug 1) and the combination of citron, serissa serissoide, hawthorn and flos Pruni mume (comparative drug 2) can reduce the content of LN, HA and PC III in the serum of rats with blood stasis collateral obstruction type hepatic fibrosis, and the effect of reducing the marker of hyperfibrosis is obviously improved when the two are used together (comparative drug 3). Evodia rutaecarpa, when used in combination with the above composition (the present invention), has a significant synergistic effect on the above composition (P <0.05 compared to comparative drug 3).
3.3 Effect on hemorheology
During the generation and development of fibrosis, various pathological products start a blood coagulation mechanism, release various vasoactive factors and cytokines, cause the abnormality of a blood coagulation-fibrinolysis system and the dysfunction of platelets of an organism, and enable blood to be in a highly condensed and viscous state. The slowness and stasis of blood flow can affect the normal perfusion of blood in the microcirculation, cause microcirculation disturbance, and aggravate cell damage and fibrotic lesions. Hemorheology can quantitatively reflect physiological and pathological changes of microcirculation. The results of the post-administration university hemorheology tests are shown in table 3.
TABLE 3 Effect on rat hemorheology
Note: p compared to model control group<0.05，**P<0.01; compared with the group of the comparative drug 3,△P<0.05，△△P<0.01。
as shown in Table 3, the composition of Salvia miltiorrhiza, Curcuma zedoaria, Curcuma longa and Rheum officinale (comparative drug 1) and the composition of Salvia miltiorrhiza, Curcumae rhizoma, Curcuma longa, Rheum officinale, citron, Serissa japonica, Crataegus pinnatifida and Prunus mume (comparative drug 3) can reduce the blood viscosity, the high blood viscosity, the medium viscosity, the low blood viscosity and the plasma viscosity of blood stasis collateral blocking type hepatic fibrosis rats, and the composition of citron, Serissa japonica, Crataegus pinnatifida and Prunus mume (comparative drug 2) has no obvious effect on the blood rheology of blood stasis collateral blocking type hepatic fibrosis rats. When the evodia rutaecarpa is used in combination with the composition (the present invention), the effect of lowering blood viscosity of the traditional Chinese medicine composition (comparative drug 3) can be enhanced (P is less than 0.05 compared with comparative drug 3).
3.4 Effect on liver histopathology
FIG. 1 is a microscopic HE staining result of rat liver tissue, and the picture shows that the normal control group rat liver lobules have complete structure, liver cords are regular and radially arranged, and liver cells have no degeneration and necrosis; the rat liver lobule structure of the model control group is disordered, the hepatic cord is broken, the hepatic cell necrosis is obvious, a large amount of lymphocytes infiltrate in a sink region, and the collagen fibers thicken and thicken; compared with the model group, the liver histopathology of the comparative drug group 4 has no obvious change, the comparative drugs groups 1, 2 and 3 have different degrees of improvement, and the liver histopathology of the invention group is improved most obviously.
FIG. 2 is the result of Masson's staining of rat liver tissue under a microscope, and the picture shows that only a small amount of collagen fibers are visible in the hepatic tissue of the normal control group in the zone of the sink; collagen fibers between the model control group vascular zone and the central vein are obviously increased to form fibrous mediastinum and complete or incomplete pseudolobule is formed by the intersection; compared with the model control group, the liver tissue collagen fibers of the comparative drug 4 group are not reduced, the liver tissue collagen fibers of the comparative drugs 1, 2 and 3 groups are reduced in different degrees, and the liver tissue collagen fibers of the invention group are obviously reduced.
4 conclusion
The traditional Chinese medicine composition can improve the liver function of a blood stasis collateral blocking type hepatic fibrosis rat, reduce the hepatic fibrosis marker content and blood viscosity in blood, improve liver histopathology and have a remarkable curative effect on the blood stasis collateral blocking type hepatic fibrosis.
Although the invention has been described in detail hereinabove with respect to a general description and specific embodiments thereof, it will be apparent to those skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (8)
1. A traditional Chinese medicine composition containing a channel-inducing medicine fructus evodiae for treating blood stasis collateral blocking type hepatic fibrosis is characterized by comprising the following raw material medicines in parts by weight: 6-15 parts of fructus evodiae, 15-45 parts of salvia miltiorrhiza, 10-30 parts of curcuma zedoary, 10-20 parts of turmeric, 15-30 parts of citron, 10-20 parts of rheum officinale, 15-40 parts of serissa serissoides, 10-25 parts of hawthorn and 10-20 parts of cupressa glauca.
2. The traditional Chinese medicine composition containing the channel-inducing medicine evodia rutaecarpa for treating blood stasis collateral blocking type hepatic fibrosis according to claim 1, which is characterized by preferably comprising the following raw material medicines in parts by weight: 9 parts of fructus evodiae, 30 parts of salvia miltiorrhiza, 20 parts of curcuma zedoary, 15 parts of turmeric, 20 parts of citron, 15 parts of rheum officinale, 30 parts of serissa serissoide, 18 parts of hawthorn and 15 parts of prunus mume.
3. A method for preparing the Chinese medicinal composition as claimed in claim 1 or 2, wherein the Chinese medicinal composition is prepared into an oral preparation.
4. The method for preparing a Chinese medicinal composition according to claim 3, wherein the oral preparation is a decoction, an oral liquid, a granule, a tablet, a capsule or a pill.
5. The preparation method of the traditional Chinese medicine composition according to claim 4, wherein the preparation method of the water decoction comprises the following steps: mixing the raw materials, adding water with the weight 4-8 times that of the mixed raw materials, soaking for 1.5-3 hours, decocting for 15-45 minutes, and filtering; adding water with the weight 5-10 times that of the filter residue into the filter residue, decocting for 30-60 minutes, and filtering; mixing the filtrates, and making into decoction.
6. The preparation method of the traditional Chinese medicine composition according to claim 4, wherein the preparation method of the granules comprises the following steps:
1) mixing and crushing evodia rutaecarpa, curcuma zedoary, curcuma longa, citron, prunus mume and serissa serissoide into coarse powder, adding 50-80% (v/v) ethanol which is 6-10 times of the weight of the coarse powder, soaking for 1-3 hours, then carrying out reflux extraction for 2-3 times, 1-2 hours each time, combining extracting solutions, recovering ethanol, concentrating the extracting solution, carrying out vacuum drying to obtain an extract, crushing the extract into fine powder, and sieving the fine powder with a 80-mesh sieve;
2) mixing the salvia miltiorrhiza, the rheum officinale and the hawthorn, adding water according to a material-liquid ratio of 1:10, soaking for 1-2 hours, performing reflux extraction, concentrating an extracting solution, drying to obtain an extract, crushing the extract into fine powder, and sieving by using a 80-mesh sieve;
3) mixing the sieved extract powder obtained in the steps 1) and 2), adding 1.0-1.5 times of microcrystalline cellulose, 0.5-0.9 times of lactose and 1.5-2.0 times of polyvinylpyrrolidone K30 aqueous solution with the mass fraction of 5% by weight of the mixed powder, uniformly mixing, granulating, drying, grading and bagging to obtain the finished product.
7. The preparation method of the traditional Chinese medicine composition according to claim 4, wherein the preparation method of the tablet comprises the following steps:
1) mixing and crushing evodia rutaecarpa, curcuma zedoary, curcuma longa, citron, prunus mume and serissa serissoide into coarse powder, adding 50-80% (v/v) ethanol which is 6-10 times of the weight of the coarse powder, soaking for 1-3 hours, then carrying out reflux extraction for 2-3 times, 1-2 hours each time, combining extracting solutions, recovering ethanol, concentrating the extracting solution, carrying out vacuum drying to obtain an extract, crushing the extract into fine powder, and sieving the fine powder with a 80-mesh sieve;
2) mixing the salvia miltiorrhiza, the rheum officinale and the hawthorn, adding water according to a material-liquid ratio of 1:10, soaking for 1-2 hours, performing reflux extraction, concentrating an extracting solution, drying to obtain an extract, crushing the extract into fine powder, and sieving by using a 80-mesh sieve;
3) mixing the sieved extract powder obtained in the step 1) and the step 2), adding 1.0-1.5 times of microcrystalline cellulose, 0.5-0.9 times of lactose, 1.5-2.0 times of polyvinylpyrrolidone K30 aqueous solution with the mass fraction of 5% and 0.03-0.07 times of talcum powder, uniformly mixing, granulating and tabletting to obtain the finished product.
8. Use of the Chinese medicinal composition of claim 1 or 2 in preparing a medicament for treating blood stasis collateral blocking type hepatic fibrosis.
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