CN105878489B

CN105878489B - Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method thereof

Info

Publication number: CN105878489B
Application number: CN201610090199.0A
Authority: CN
Inventors: 涂翔; 钟森
Original assignee: Individual
Current assignee: Individual
Priority date: 2015-02-17
Filing date: 2016-02-17
Publication date: 2020-01-14
Anticipated expiration: 2036-02-17
Also published as: CN106138102A; CN105878490A; CN105878490B; CN105878325A; CN105878489A; CN105878488A; CN106138144A; CN105878321A; CN106138344A; CN105878326A; CN106138152A

Abstract

The invention belongs to the field of medicines, and particularly relates to a pharmaceutical composition for inhibiting tumor angiogenesis and a preparation method thereof.

Description

Pharmaceutical composition for inhibiting tumor angiogenesis and preparation method thereof

Technical Field

Background

Angiogenesis is the process of sprouting new blood vessels from existing blood vessels. This process is associated with vascular endothelial cell migration and proliferation. The process of embryonic development is accompanied by angiogenesis. But angiogenesis rarely occurs in adults, except for wound healing, female menstrual periods, and some pathological processes (such as cancer).

Angiogenesis is of great importance to the growth, metastasis and prognosis of malignant solid tumors. Angiogenesis is necessary for further growth of malignant solid tumors after they break through the epithelial basement membrane. The newly formed blood vessel in tumor has its own unique structural characteristics, is represented by incomplete vessel wall, has no smooth muscle component, and is only composed of porous endothelial cells and sheet basement membrane. Most scholars believe that the structural features of the new blood vessels make it possible for distant metastasis of malignant tissues. Therefore, quantification of new blood vessels in malignant solid tumors is considered to be an important independent prognostic marker.

Carapax Trionycis is the dorsal scale of Trionyx sinensis Wiegmann of Trionychidae. Salty and cold in nature. Nourish yin and suppress yang, soften hardness and dissipate nodulation, defervesce and remove steaming. Can be used for treating fever due to yin deficiency, internal stirring of deficiency wind, amenorrhea, abdominal mass, and malaria. The using amount is 9-24 g. Modern medicine shows that processed products of turtle shells include two kinds, namely turtle shell and vinegar turtle shell. Modern studies have shown that turtle shells contain collagen (collagen), calcium carbonate, calcium phosphate, iodine, etc. The extract content of carapax Trionycis is the most. The dorsal and ventral scallion contain 11 elements such as calcium, phosphorus, sodium, magnesium, potassium, zinc, iron, manganese, cobalt, copper, arsenic, etc. The pharmacological effects are as follows:

1. strengthening action: the turtle polysaccharide is administrated by intragastric administration for 15-20 days at a ratio of 0.5 g/kg, 1.0 g/kg and 2.0g/kg, and can significantly improve anoxia tolerance and anti-freezing effect of mice, prolong swimming time of mice, and resist fatigue.

2. The immunity promoting effect is as follows: the turtle polysaccharide is perfused for 15-20 days at the concentration of 0.5, 1.0 and 2.0g/kg, so that the hemolytic capacity of plaque forming cells of the mice can be obviously improved, and the generation of hemolysin antibodies can be promoted; and enhance delayed type hypersensitivity of mice.

3. Has antitumor effect. The turtle shell powder is orally taken at 280mg/kg, has an inhibiting effect on mouse transplanted parenchymal cancer MH134, reduces the diameter of a tumor, and obviously lightens the weight of the tumor. Has no obvious effect on ascites carcinoma. The nude mice inoculated with human intestinal cancer cells take turtle shell powder orally at a dose of 800mg/kg every day, after 35 days of treatment, compared with a control group, the tumor inhibition rate is 92.15%, the tumor necrosis area reaches 67%, compared with a 5-fluorouracil (5-Fu) group, the nude mice have the advantage of not causing the decrease of the number of host leucocytes, which indicates that the turtle shell powder has the inhibition effect on human intestinal cancer, small side effect and far lighter inhibition on bone marrow than 5-Fu.

4. And (3) the other: soaking Bufo siccus in 0.5% or 1.0% turtle polysaccharide Renger solution to increase contraction height and line area and prolong continuous contraction time. The product can inhibit proliferation of connective tissue, and eliminate agglomeration; it also has the effect of increasing plasma protein, and can be used for treating anemia caused by liver disease.

Radix Rhapontici is the dried root of Asteraceae plant Agkistrodon japonicus. Bitter in taste and cold in nature. Has the effects of clearing away heat and toxic materials, eliminating carbuncle, promoting lactation, relaxing muscles and tendons, and dredging collaterals. Can be used for treating acute mastitis, swelling and pain, carbuncle, cellulitis, sore, scrofula, breast milk obstruction, and spasm due to damp arthralgia. The application amount is 5-9 g. Modern researches show that the rhaponticum uniflorum has the following pharmacological actions:

1. has effects on central nervous system, and the like with the effect of Echinacea alkaloid, and small dose can excite animal, large dose can cause spasm, and later general inhibition can occur, and the medicine has reviving effect on sleep of mice caused by barbital, and can excite neuromuscular device and promote recovery process of peripheral nerve.

2. The influence on cardiovascular system, the echinocandin can cause blood pressure reduction and cardiac contractility enhancement to anaesthetized cats, the cardiac contractility tension can be increased and the contraction amplitude can be weakened to the isolated frog heart, the high concentration can stop the systolic period of the heart, and the isolated rabbit ear can show vasodilatation.

3. In addition, echinocandin can increase the tension of the isolated intestinal canal of the cat and inhibit the isolated intestinal canal of the rabbit.

The pericarpium Citri Reticulatae viride is pericarp of dried young fruit or immature fruit of Citrus reticulata Blanco of Rutaceae and its cultivar. Bitter and pungent in flavor and warm in nature. Has the effects of soothing liver, breaking qi, removing food retention and resolving stagnation. Can be used for treating distending pain in chest and hypochondrium, hernia pain, nodules of breast, mammary abscess, food stagnation, qi stagnation, and abdominal pain. The usage amount is 3-l 0 g. The processed product of pericarpium Citri Reticulatae viride includes pericarpium Citri Reticulatae viride and vinegar pericarpium Citri Reticulatae viride.

Flos Chrysanthemi Indici is the dry head-shaped inflorescence of wild Chrysanthemum of Compositae, and has slightly cold nature and bitter and pungent taste. Has the effects of clearing away heat and toxic materials, dispelling pathogenic wind, and calming the liver. Can be used for treating furuncle, carbuncle, swelling, conjunctival congestion, swelling and pain, headache, and vertigo. The application amount is 9-15 g. Modern researches show that the wild chrysanthemum can treat respiratory tract inflammation, cervicitis, carbuncle, furuncle, cold, upper respiratory tract infection and the like.

Although turtle shells, radix rhapontici, pericarpium citri reticulatae viride and wild chrysanthemum flowers are reported to have an anti-tumor effect, the anti-tumor effect on angiogenesis is not found.

Disclosure of Invention

The invention solves the first technical problem of providing a pharmaceutical composition for inhibiting tumor angiogenesis.

The pharmaceutical composition of the invention takes uniflower swisscentaury root and green tangerine orange peel or vinegar green tangerine orange peel as raw material medicines, and the weight ratio is as follows:

1-10 parts of uniflower swisscentaury root, and 1-10 parts of green tangerine peel or vinegar green tangerine peel;

preferably, 2-8 parts of uniflower swisscentaury root and 2-8 parts of green tangerine peel or vinegar green tangerine peel;

most preferably 5 parts of uniflower swisscentaury root, and 5 parts of green tangerine peel or vinegar green tangerine peel.

The pharmaceutical composition for inhibiting tumor angiogenesis is a medicament prepared by taking uniflower swisscentaury root, green tangerine orange peel or vinegar green tangerine peel as main raw materials and adding pharmaceutically conventional auxiliary materials according to a pharmaceutically conventional method.

In the technical scheme, the medicament is an oral preparation or an injection. The medicine is administered by oral administration, intramuscular injection, intravenous infusion or intraperitoneal injection.

In the technical scheme, the oral preparation is water decoction, powder, granules, capsules, tablets, oral liquid, mixture or syrup.

In the technical scheme, the conventional auxiliary materials comprise diluents, excipients, fillers, adhesives, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants and the like which are conventional in the pharmaceutical field.

The second technical problem to be solved by the present invention is to provide a method for preparing the pharmaceutical composition for inhibiting tumor angiogenesis in the above technical scheme, which comprises the following steps:

the method comprises the following steps: pulverizing the raw materials into fine powder, and mixing to obtain powder; or

The second method comprises the following steps: pulverizing the above materials into fine powder, and making into capsule; or

The third method comprises the following steps: pulverizing the raw materials into fine powder, and tabletting to obtain tablet; or

The method four comprises the following steps: decocting the raw materials with water, and filtering to obtain decoction; or

The method five comprises the following steps: decocting the raw materials with water, filtering to obtain decoction, and drying the decoction; or

The method six: decocting the raw materials with water, concentrating the extractive solution, and granulating to obtain granule; or

The method comprises the following steps: decocting the above materials with water, concentrating the extractive solution, granulating, and making into capsule; or

The method eight: decocting the above materials with water, concentrating the extractive solution, granulating, and tabletting to obtain tablet; or

The method comprises the following steps: decocting the above materials in water, and making into decoction, or adding conventional adjuvants to make into oral liquid, syrup, and mixture.

In the technical scheme, the water content of the dried decoction liquid is lower than 5 percent in the method five.

The composition can be made into oral preparation or injection, and the conventional adjuvants include diluent, excipient, filler, binder, humectant, disintegrant, absorption enhancer, surfactant, adsorption carrier, lubricant, etc.

In conclusion, the pharmaceutical composition for inhibiting tumor angiogenesis has the advantages of obvious curative effect, safety and no toxicity, and provides a brand new choice for clinically inhibiting tumor angiogenesis and treating tumors.

Drawings

FIG. 1 photomontage of juvenile fish with turtle shell intervention

FIG. 2 shows fluorescence microscopy of turtle Shell intervened juvenile fish

FIG. 3 shows fluorescence microscopy images of turtle Shell intervened in the dorsal aorta of juvenile fish

FIG. 4 light mirror image of juvenile fish with intervention of green tangerine peel

FIG. 5 fluorescent microscope display of immature fish with green skin intervention

FIG. 6 fluorescent microscope display of the dorsal aorta of young fish with intervention of pericarpium Citri Reticulatae viride

FIG. 7 optical lens drawing of the intervention of wild chrysanthemum flowers for juvenile fish

FIG. 8 fluorescence microscopy display of wild chrysanthemum interfered juvenile fish

FIG. 9 is a fluorescent microscope display of the aorta dorsum of the young fish intervened by wild chrysanthemum

FIG. 10 light mirror image of larval fish with reed-dropping intervention

FIG. 11 fluorescence microscopy display of Rhapontic intervened juvenile fish

FIG. 12 is a fluorescent microscope image of the aorta dorsum of young fish with rhaponticum uniflorum intervention

FIG. 13 light microscopy of juvenile fish for positive control-PTK 787 intervention

FIG. 14 fluorescence microscopy of juvenile fish with positive control-PTK 787 intervention

FIG. 15 Positive control-PTK 787 Interferon juvenile Fish Back aorta fluorescence microscopy display

FIG. 16 negative Control-light microscopy of juvenile fish with Vehicle Control (0.1% DMSO) intervention

FIG. 17 shows fluorescence microscopy of juvenile fish with negative Control-Vehicle Control (0.1% DMSO) intervention

FIG. 18 shows the negative Control-vessel Control (0.1% DMSO) intervened by the fluorescence microscopy of the dorsal aorta of young fish

Detailed Description

The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.

Firstly, the test for inspecting the inhibition of tumor angiogenesis by using turtle shells, uniflower swisscentaury roots, green tangerine peels and wild chrysanthemum flowers is as follows:

1. materials and methods

1.1 materials

The Chinese herbs were purchased from Sichuan Huichun Tang medicine Co. All reagents were purchased from Sigma-Aldrich Co, (st. louis, MO), PTK787(vatalanib) from seleckchem. The experiment was performed using fli1a-EGFP transgenic zebrafish. The zebra fish is bred according to a standard environment.

1.2 preparation of reagents

Weighing 450g of traditional Chinese medicine, decocting with 8 times of water for 3 times, each time for 1 hour, combining the 3 water decoctions, concentrating to about 400ml on a 800W electric furnace, passing through a 100-mesh screen (residue sample), uniformly coating the mixture in an evaporating dish, placing the evaporating dish in an electric heating forced air drying oven, drying discontinuously at 60 ℃ for 62 hours, and continuing to dry in a glass drier at room temperature until an extract with the moisture content of less than 5% (determined by a drying method) is prepared.

1.3 Experimental procedures

Embryos at 22 hours post fertilization were placed in 12-well plates (30 embryos per well) and intervened with the chinese medicine for 26 hours. The Chinese medicinal water extract is dissolved in 0.1% dimethyl sulfoxide (DMSO), and the concentration of the Chinese medicinal water extract added into each well is 200 μ g/ml. The positive control group was 5 μ g/ml PTK787 (Wattanib vatalanib, a vascular endothelial growth factor receptor antagonist) and the negative control group was 0.1% DMSO. At 48 hours post fertilization, the young fish were anesthetized with tricaine and photographed using Nikon SMZ 1500 fluorescence microscopy analysis. Internode blood vessel formation is the main index for evaluating the effect of traditional Chinese medicine. And simultaneously, the toxicity of the traditional Chinese medicine is also evaluated.

1.4 results and conclusions

The light microscope picture, fluorescence microscope picture and back aorta fluorescence microscope picture of the juvenile fish intervened by turtle shell, radix Rhapontici, green tangerine orange peel, wild chrysanthemum, positive control-PTK 787 and positive control-PTK 787 are respectively shown in figures 1-18.

All 30 juvenile fishes intervened by 4 traditional Chinese medicines of turtle shell, radix rhapontici, green tangerine orange peel and wild chrysanthemum flower and PTK787 have angiogenesis defects. Light microscope and fluorescence microscope show that compared with the negative control of 0.1% DMSO, juvenile fish intervened by 4 traditional Chinese medicines of turtle shell, uniflower swisscentaury root, green tangerine orange peel and wild chrysanthemum flower forms fewer complete internode blood vessels. The high power mirror showed that the dorsal aortic seedling could only be observed occasionally. The 5. mu.g/ml PTK787 positive control was able to completely inhibit the internodal and dorsal longitudinal vessels. The traditional Chinese medicine does not cause death or teratogenesis of the zebra fish. No neurotoxicity or organ toxicity of the Chinese medicine was found.

Secondly, the experiment for investigating the combined application of the turtle shell, the uniflower swisscentaury root, the green tangerine orange peel and the wild chrysanthemum flower for inhibiting the tumor angiogenesis is as follows:

1. materials and methods

1.1 materials

Carapax Trionycis, radix Rhapontici, pericarpium Citri Reticulatae viride, and flos Chrysanthemi Indici are all available from Sichuan Huichun Tang pharmaceutical Co. All reagents were purchased from Sigma-Aldrich co. (st. The experiment was performed using fli1a-EGFP transgenic zebrafish. The zebra fish is bred according to a standard environment.

1.2 preparation of reagents

Weighing 500g of traditional Chinese medicine, decocting with 8 times of water for 3 times, each time for 1 hour, combining the 3 water decoctions, concentrating to about 400ml on a 800W electric furnace, passing through a 100-mesh screen (residue sample), uniformly coating the mixture in an evaporating dish, placing the evaporating dish in an electric heating forced air drying oven, drying discontinuously at 60 ℃ for 62 hours, and continuing to dry in a glass drier at room temperature until an extract with the moisture content of less than 5% (determined by a drying method) is prepared.

Wherein, when the traditional Chinese medicines are applied singly, 500g of turtle shell, uniflower swisscentaury root, green tangerine orange peel and wild chrysanthemum are respectively weighed; when the Chinese medicines are combined in pairs, 250g of turtle shell, uniflower swisscentaury root, green tangerine peel and wild chrysanthemum are respectively weighed and then mixed according to compatibility for use; when the three traditional Chinese medicines are combined for application, 167g of turtle shell, uniflower swisscentaury root, green tangerine peel and wild chrysanthemum are respectively weighed and then mixed according to compatibility for use; when the four traditional Chinese medicines are combined for application, 125g of turtle shell, uniflower swisscentaury root, green tangerine orange peel and wild chrysanthemum flower are respectively weighed and mixed for use.

1.3 Experimental procedures

Embryos at 22 hours post fertilization were placed in 12-well plates (30 embryos per well) and intervened with the chinese medicine for 26 hours. The Chinese medicinal water extract is dissolved in 0.1% dimethyl sulfoxide (DMSO), and the concentration of the Chinese medicinal water extract added into each well is 200 μ g/ml. At 48 hours post fertilization, the young fish were anesthetized with tricaine and photographed using Nikon SMZ 1500 fluorescence microscopy analysis. The number and inhibition rate of intact internode blood vessels are the main indexes for evaluating the effect of the traditional Chinese medicine. The number of intact internodal vessels (ISVs) was counted, i.e.: the number of internodal vessels connecting the Dorsal Aorta (DA) to the Dorsal Longitudinal Anastomotic Vein (DLAV). Data results are expressed as means (minimum, maximum). The inhibition rate was calculated according to the following formula:

inhibition ratio (%) - (1-ISV)_{Number of Chinese herbs}/ISV_{Number of negative control groups})×100。

1.4 the results are as follows:

1.4.1 pairwise combination results are shown in tables 1-6:

TABLE 1 quantitative comparison of the inhibition of neovascularization by Rhapontic Swisscents + wild Chrysanthemum

The results show that the effect of the combination of the uniflower swisscentaury root and the wild chrysanthemum flower on inhibiting the neovascularization is very significant and different from the effect of the uniflower swisscentaury root on inhibiting the neovascularization (P < 0.01); compared with wild chrysanthemum, the difference has no statistical significance, but the inhibition rate is still improved.

TABLE 2 quantitative comparison of Rhaponticus and Citrus reticulata Blanco for angiogenesis inhibition

The results show that the effect of the radix rhapontici and pericarpium citri reticulatae viride combination on inhibiting the new blood vessels is very significant and different from that of the radix rhapontici statistically (P is less than 0.01); compared with green tangerine orange peel, the difference is very significant (P <0.001) in statistical significance.

TABLE 3 quantitative comparison of the inhibition of neovascularization by wild chrysanthemum and green tangerine orange peel

The results show that the effect of the combination of the wild chrysanthemum flower and the green tangerine peel for inhibiting the neovascularization is very significant difference (P is less than 0.01) with statistical significance compared with the wild chrysanthemum flower; compared with green tangerine orange peel, the difference is very significant (P <0.001) in statistical significance.

TABLE 4 quantitative comparison of inhibition of neovascularization by turtle Shell + wild chrysanthemum

The results show that compared with turtle shells, the effect of the combination of turtle shells and wild chrysanthemum flowers on inhibiting the neovascularization has extremely significant difference (P is less than 0.01) with statistical significance; compared with wild chrysanthemum, the difference has no statistical significance, but the inhibition rate is still improved.

TABLE 5 quantitative comparison of inhibition of neovascularization by turtle Shell + Rhaponticus

The results show that compared with turtle shells, the effect of the combination of turtle shells and uniflower swisscentaury on inhibiting the neovascularization has very significant difference (P is less than 0.01) in statistical significance; compared with uniflower swisscentaury, the difference is very significant in statistical significance (P < 0.001).

TABLE 6 quantitative comparison of inhibition of neovascularization by turtle Shell + Green Tangerine Peel

The results show that compared with turtle shells, the effect of the combination of turtle shell and green tangerine peel for inhibiting the neovascularization has extremely significant difference (P is less than 0.01) with statistical significance; compared with green tangerine orange peel, the difference is very significant (P <0.001) in statistical significance.

1.4.2 the results are shown in tables 7-10:

TABLE 7 quantitative comparison of Rhaponticus, Chrysanthemum indicum and Citrus reticulata viride for angiogenesis inhibition

The above results show that the effect of the combination of radix Rhapontici + flos Chrysanthemi Indici + pericarpium Citri Reticulatae viride in inhibiting angiogenesis is very significant (P <0.01) compared with the effect of using radix Rhapontici, pericarpium Citri Reticulatae viride and flos Chrysanthemi Indici alone. Compared with the radix rhapontici and pericarpium Citri Reticulatae viride, the combination of radix Rhapontici, flos Chrysanthemi Indici and pericarpium Citri Reticulatae viride has a very significant difference (P <0.01) in statistical significance; compared with the uniflower swisscentaury root and wild chrysanthemum, the major difference (P <0.05) in statistical significance exists; compared with wild chrysanthemum flower and green tangerine peel, the difference has no statistical significance, but the inhibition rate is still slightly improved.

TABLE 8 quantitative comparison of the inhibition of neovascularization by wild chrysanthemum flower, turtle shell and green tangerine peel

The results show that the combination of wild chrysanthemum, turtle shell and green tangerine orange peel has a very significant difference (P <0.01) in statistical significance in the effect of inhibiting the neovascularization compared with the effect of singly using turtle shell, green tangerine orange peel and wild chrysanthemum. Compared with the combination of turtle shell and green tangerine orange peel, the combination of the wild chrysanthemum, the turtle shell and the green tangerine orange peel has extremely obvious effect of inhibiting the neovascularization (P is less than 0.01); compared with wild chrysanthemum flower and turtle shell, the difference is significant in statistical significance (P is less than 0.05); compared with wild chrysanthemum flower and green tangerine peel, the difference has no statistical significance, but the inhibition rate is still slightly improved.

TABLE 9 quantitative comparison of the inhibition of neovascularization by wild chrysanthemum flower + turtle shell + rhaponticum uniflorum

The results show that the effect of the combination of the wild chrysanthemum, the turtle shell and the uniflower swisscentaury root for inhibiting the neovascularization is very significant (P is less than 0.01) compared with the effect of singly using the turtle shell and the uniflower swisscentaury root; compared with the wild chrysanthemum alone, the wild chrysanthemum has statistically significant difference (P < 0.05). Compared with the combination of turtle shell and uniflower swisscentaury root, the combination of the wild chrysanthemum, the turtle shell and the uniflower swisscentaury root has a statistically significant difference (P is less than 0.05); compared with the wild chrysanthemum flower + turtle shell and the wild chrysanthemum flower + uniflower swisscentaury root, the difference is not statistically significant, but the inhibition rate is still slightly improved.

TABLE 10 quantitative comparison of inhibition of neovascularization by turtle shell + green tangerine orange peel + rhaponticum uniflorum

The results show that the effect of the combination of turtle shell, green tangerine orange peel and uniflower swisscentaury root on inhibiting the neovascularization is very different from that of the combination of turtle shell, green tangerine orange peel and uniflower swisscentaury root which is singly used in a statistical sense (P is less than 0.01). Compared with the combination of the green tangerine orange peel and the uniflower swisscentaury root, the combination of the turtle shell, the green tangerine orange peel and the uniflower swisscentaury root has extremely obvious statistically significant difference (P is less than 0.01); compared with turtle shell and uniflower swisscentaury, the difference is statistically significant (P is less than 0.05); compared with turtle shell and green tangerine peel, the difference has no statistical significance, but the inhibition rate is still slightly improved.

1.4.3 the four combination results are shown in Table 11:

TABLE 11 quantitative results of inhibition of neovascularization by turtle shell + rhaponticum uniflorum + green tangerine orange peel + wild chrysanthemum flower

The above results show that:

1) compared with the single use of turtle shell, radix rhapontici, pericarpium citri reticulatae viride and flos chrysanthemi indici, the effect of the radix rhapontici, flos chrysanthemi indici + pericarpium citri reticulatae viride and turtle shell combination for inhibiting the neovascularization has extremely obvious difference (P is less than 0.01) with statistical significance.

2) The effect of the combination of the uniflower swisscentaury root, the wild chrysanthemum flower, the green tangerine peel and the turtle shell for inhibiting the neovascularization is compared with the combination of the turtle shell, the uniflower swisscentaury root, the green tangerine peel and the wild chrysanthemum flower in pairs: compared with the uniflower swisscentaury root and green tangerine peel, the uniflower swisscentaury root and wild chrysanthemum flower, the turtle shell and green tangerine peel, the turtle shell and the uniflower swisscentaury root, the statistical significance difference is very significant (P is less than 0.01); compared with wild chrysanthemum flower and green tangerine peel, the difference has no statistical significance, but the inhibition rate is still slightly improved.

3) The effect of the combination of the uniflower swisscentaury root, the wild chrysanthemum flower, the green tangerine peel and the turtle shell for inhibiting the neovascularization is compared with the combination of the turtle shell, the uniflower swisscentaury root, the green tangerine peel and the wild chrysanthemum flower in pairs: compared with wild chrysanthemum flower, turtle shell, uniflower swisscentaury root and turtle shell, green tangerine orange peel and uniflower swisscentaury root, the statistical significance difference is achieved (P is less than 0.05); compared with the wild chrysanthemum flower, turtle shell, green tangerine orange peel and the uniflower swisscentaury root, wild chrysanthemum flower and green tangerine orange peel, the inhibition rate is still slightly improved although the difference has no statistical significance.

In conclusion, the turtle shell, the uniflower swisscentaury root, the green tangerine peel and the wild chrysanthemum flower adopted by the invention can be used as medicines singly or in combination, and no incompatibility appears during combination use, so that the traditional Chinese medicine composition has an obvious effect on inhibiting tumor angiogenesis, and provides a brand new choice for clinically inhibiting tumor angiogenesis and treating tumors.

Claims

1. A pharmaceutical composition for inhibiting tumor angiogenesis, comprising: the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight:

2-8 parts of uniflower swisscentaury root and 2-8 parts of green tangerine orange peel or vinegar green tangerine orange peel.

2. The pharmaceutical composition for inhibiting tumor angiogenesis according to claim 1, wherein: the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight:

5 parts of uniflower swisscentaury root and 5 parts of green tangerine peel or vinegar green tangerine peel.

3. The pharmaceutical composition for inhibiting tumor angiogenesis according to claim 1 or 2, wherein: the medicine is prepared by taking radix rhapontici, pericarpium citri reticulatae viride or vinegar pericarpium citri reticulatae viride as raw material medicines and adding pharmaceutically conventional auxiliary materials according to a pharmaceutically conventional method.

4. The pharmaceutical composition for inhibiting tumor angiogenesis according to claim 3, wherein: the medicament is an oral preparation or an injection.

5. The pharmaceutical composition for inhibiting tumor angiogenesis according to claim 4, wherein: the oral preparation is water decoction, powder, granule, capsule, tablet, oral liquid, mixture or syrup.

6. The method for preparing the pharmaceutical composition for inhibiting tumor angiogenesis according to claim 1 or 2, wherein the pharmaceutical composition comprises: the method comprises the following steps:

7. The method for preparing a pharmaceutical composition for inhibiting tumor angiogenesis according to claim 6, wherein: method five the dried decoction is brought to a water content of less than 5%.