CN104225463B - Traditional Chinese medicine composition for treating hormone-dependent tumors and preparation method of traditional Chinese medicine composition - Google Patents

Traditional Chinese medicine composition for treating hormone-dependent tumors and preparation method of traditional Chinese medicine composition Download PDF

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CN104225463B
CN104225463B CN201410426304.4A CN201410426304A CN104225463B CN 104225463 B CN104225463 B CN 104225463B CN 201410426304 A CN201410426304 A CN 201410426304A CN 104225463 B CN104225463 B CN 104225463B
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radix
chinese medicine
medicine composition
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CN104225463A (en
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蔡大勇
王月崎
李萍萍
邹忠梅
孙红
王秀萍
邓博
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Beijing deyitang Pharmaceutical Co., Ltd
Institute of Medicinal Plant Development of CAMS and PUMC
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Abstract

The invention discloses a traditional Chinese medicine composition for treating hormone-dependent tumors and a preparation method of the traditional Chinese medicine composition, belonging to the field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following components in parts by weight: 8-20 parts of Chinese thorowax root, 4-23 parts of turmeric root-tuber, 2-23 parts of astragalus, 1-18 parts of tangerine peel, 1-20 parts of danshen root, 1-18 parts of gamboge, 1-17 parts of root-bark of tree peony, 1-17 parts of liquoric root, 1-17 parts of sophora flower, 1-17 parts of redroot gromwell root, 1-17 parts of common selfheal fruit-spike and 1-17 parts of curcuma zedoary. According to the traditional Chinese medicine composition disclosed by the invention, by virtue of the collaborative compatibility effects among the traditional Chinese medicine components, the traditional Chinese medicine composition can be effectively used for treating the hormone-dependent tumors particularly hormone-dependent breast cancer, is significant in curative effect and small in side effect, and can be used for improving the survival rate and survival quality of patients taking the composition.

Description

A kind of Chinese medicine composition being used for the treatment of hormone-dependent tumor and preparation method thereof
Technical field
The present invention relates to the field of Chinese medicines, particularly a kind of Chinese medicine composition being used for the treatment of hormone-dependent tumor and preparation method thereof.
Background technology
The malignant tumor that the propagation that hormone-dependent tumor, especially hormone-dependent breast cancer refer to cancerous cell controls by hormone, usually occurs in breast glandular epithelium tissue, is one of common malignant tumor of women.According to statistics, breast cancer incidence accounts for the 7-10% of the various Cancer Mortality of whole body, and the especially normal women sent out between 40 ~ 60 years old, before and after menopause, has a strong impact on patient's physical and mental health, even jeopardize patient vitals.So to hormone-dependent tumor, especially the treatment of hormone-dependent breast cancer is very necessary.
At present in the treatment clinical course of hormone-dependent tumor, the main medicine used has following several;
1) tamoxifen: three oxygen aniline are the non-steroidal estrogen antagonist kind anti-cancer drugs of chemosynthesis, but its side effect is larger, such as, make user's endocrine-metabolic anomaly, cause the increase of flush, hectic fever, body weight, Nausea and vomiting, have harmful effect to liver, nervus centralis, cardiovascular and reproductive system etc.And it is cloudy and embryonal breast carcinoma is invalid to three.
2) Trastuzumab: Trastuzumab is the Humanized monoclonal antibodies that recombinant DNA derives, but user can cause vasodilation after using, there are dyspepsia, nausea and vomiting, depression, anxiety, many toxic and side effects such as dizzy, and cloudy and embryonal breast carcinoma is invalid to three.
3) paclitaxel: the effective Chinese medicine monomer of paclitaxel, but resource is extremely limited, causes it expensive.
Inventor finds that prior art at least exists following problem:
The side effects of pharmaceutical drugs that prior art provides are large, and therapeutical effect lacks the specificity that hormone relies on.
Summary of the invention
Embodiment of the present invention technical problem to be solved is, provides little Chinese medicine composition being used for the treatment of hormone-dependent tumor of a kind of side effect and preparation method thereof.Concrete technical scheme is as follows:
First aspect, embodiments provide a kind of Chinese medicine composition being used for the treatment of hormone-dependent tumor, comprise the composition of following weight portion: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
As preferably, described Chinese medicine composition comprises the composition of following weight portion: Radix Bupleuri 13-15 part, Radix Curcumae 9-18 part, Radix Astragali 7-18 part, Pericarpium Citri Reticulatae 3-15 part, Radix Salviae Miltiorrhizae 3-17 part, Resina garciniae 3-15 part, Cortex Moutan 2-12 part, Radix Glycyrrhizae 2-12 part, Flos Sophorae 2-12 part, Radix Arnebiae (Radix Lithospermi) 2-12 part, Spica Prunellae 2-12 part, Rhizoma Curcumae 2-12 part.
Particularly, the dosage form of described Chinese medicine composition is tablet, capsule, pill, granule, Emulsion, ointment, spray, slow releasing preparation, Controlled release formulation or particles medication agents.
Second aspect, embodiments provides a kind of medicine, comprises any one Chinese medicine composition above-mentioned for the treatment of effective dose.
Further, described medicine also comprises the other drug composition with described Chinese medicine composition compatibility, and pharmaceutically acceptable carrier and/or adjuvant.
Particularly, described adjuvant is dextrin and aspartame.
The third aspect, embodiments provides a kind of preparation method of Chinese medicine composition, comprising:
Step a, Radix Bupleuri, Radix Salviae Miltiorrhizae, Resina garciniae, Pericarpium Citri Reticulatae, Flos Sophorae, Cortex Moutan, Radix Arnebiae (Radix Lithospermi), Radix Curcumae, Rhizoma Curcumae to be mixed and after pulverizing, obtain mixture, weight is utilized to be that the ethanol that described mixture weight 8-10 volume fraction is doubly 70-90% carries out extraction 2-3 time to described mixture, each 1-3h, obtain the first extracting solution and medicinal residues
Step b, carry out concentrating under reduced pressure to described first extracting solution, obtain the first thick paste, the proportion of described first thick paste is 1.2-1.5;
Step c, utilize weight to be described medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae gross weight the mixture of 10-12 water doubly to described medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae carry out extraction 2-3 time, each 1-1.5h, obtain the second extracting solution;
Steps d, carry out concentrating under reduced pressure to described second extracting solution, obtain the second thick paste, the proportion of described second thick paste is 1.2-1.5;
Step e, by described first thick paste and described second thick paste mixing, and be processed into Chinese medicine preparation, obtain described Chinese medicine composition;
In described Chinese medicine composition, the weight proportion of each composition is: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
Further, described step e comprises: by described first thick paste and described second thick paste mixing, add dextrin and aspartame, mix homogeneously, using volume fraction be the ethanol of 85% as wetting agent, described Chinese medicine composition is processed into Chinese medicinal granule;
The weight ratio of described Chinese medicinal granule and described aspartame is 1:0.008-0.012;
The weight ratio of described Chinese medicinal granule and described dextrin is 1:0.7-1.2.
Fourth aspect, the embodiment of the present invention additionally provides a kind of preparation method of Chinese medicine composition, comprising:
Step α, Radix Bupleuri, the Radix Astragali, Pericarpium Citri Reticulatae, Radix Salviae Miltiorrhizae, Resina garciniae, Cortex Moutan, Radix Glycyrrhizae, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) and Spica Prunellae mixed and carries out water boiling and precipitation with ethanol after pulverizing, obtaining the 3rd extracting solution;
Step β, Radix Curcumae, Rhizoma Curcumae mixed and extracts after pulverizing, obtaining volatile oil;
Step γ, by described 3rd extracting solution and described volatile oil mix homogeneously, and be processed into Chinese medicine preparation, obtain described Chinese medicine composition;
In described Chinese medicine composition, the weight proportion of each composition is: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
Further, described step γ comprises: after described 3rd extracting solution and described volatile oil mix homogeneously, utilize volume fraction be 5% propylene glycol carry out microemulsified, then utilize concentration be the soybean oil of 40% as outer oil phase, described Chinese medicine composition is processed into drop pill.
The beneficial effect that the technical scheme that the embodiment of the present invention provides is brought is:
On the one hand, the Chinese medicine composition that the embodiment of the present invention provides, by the Radix Bupleuri of 8-20 part, Radix Curcumae part of 4-23g, the Radix Astragali of 2-23 part, the Pericarpium Citri Reticulatae of 1-18 part, the Radix Salviae Miltiorrhizae of 1-20 part, the Resina garciniae of 1-18 part, the Cortex Moutan of 1-17 part, the Radix Glycyrrhizae of 1-17 part, the Flos Sophorae of 1-17 part, the Radix Arnebiae (Radix Lithospermi) of 1-17 part, collaborative compatibility effect between the Spica Prunellae of 1-17 part and the Rhizoma Curcumae of 1-17 part, this Chinese medicine composition is enable to be effective to hormone-dependent tumor, especially the treatment of hormone-dependent breast cancer, not only evident in efficacy, and side effect is little, improve survival rate and the life quality of medication patient.
On the other hand, embodiments providing a kind of preparation method of Chinese medicine composition, by extracting the active component in above-mentioned each Chinese medicine ingredients, improve the utilization rate of Chinese medicine ingredients, and concentrating under reduced pressure is carried out to extracting solution, prepare the Chinese medicine composition that drug effect is good.The method is simple to operation, is convenient to large-scale industrial and produces.
Accompanying drawing explanation
In order to be illustrated more clearly in the technical scheme in the embodiment of the present invention, below the accompanying drawing used required in describing embodiment is briefly described, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skill in the art, under the prerequisite not paying creative work, other accompanying drawing can also be obtained according to these accompanying drawings.
Fig. 1 is the optical microscope figure of the mammary gland tissue after the HE dyeing of each group of nude mice that the embodiment of the present invention 6 provides;
Fig. 2 is the optical microscope figure of the uterine cancer cell after the HE dyeing of each group of nude mice that the embodiment of the present invention 6 provides;
Fig. 3 is the optical microscope figure of the ovary tissue after the HE dyeing of each group of nude mice that the embodiment of the present invention 6 provides.
Wherein, in above-mentioned each accompanying drawing, × 100, × 200 and × 400 amplifications referring to optical microscope are respectively 100,200 and 400.
Detailed description of the invention
For making technical scheme of the present invention and advantage clearly, below in conjunction with accompanying drawing, embodiment of the present invention is described further in detail.
First aspect, embodiments provide a kind of Chinese medicine composition being used for the treatment of hormone-dependent tumor, comprise the composition of following weight portion: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
Inventor passes through hormone-dependent tumor, especially the pathogeny of hormone-dependent breast cancer is studied, take the treatment of eliminating pathogenic factor for supporting vital QI, select above-mentioned several Chinese medicine ingredients in conjunction with pharmacology and be applied to clinical, good effect is achieved to the treatment of above-mentioned disease.The pharmacological action of above-mentioned each Chinese medicine ingredients is as follows:
Radix Bupleuri, Radix Curcumae is soothing the liver, and Cortex Moutan is regulated the flow of vital energy, and is monarch drug altogether; Radix Astragali QI invigorating, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) removing heat from blood are ministerial drug altogether; Rhizoma Curcumae, Radix Salviae Miltiorrhizae, Resina garciniae, Spica Prunellae blood stasis-eliminating and stagnation-dissipating are adjuvant drug altogether; Pericarpium Citri Reticulatae, Radix Glycyrrhizae coordinating the actions of various ingredients in a prescription, priming return through, altogether for making medicine.
Visible, the Chinese medicine composition that the embodiment of the present invention provides, by the collaborative compatibility effect between above-mentioned each composition, this Chinese medicine composition is enable to be effective to hormone-dependent tumor, especially the treatment of hormone-dependent breast cancer, effectively improve tired, the indigestion and loss of appetite symptom such as to become thin of the common depression agitation of patient, distending pain of the breast, scleroma unbounded, hectic fever, evident in efficacy.And the side effect of this Chinese medicine composition is little, patient takes safer, and improves survival rate and the life quality of medication patient.In addition, each Chinese medicine ingredients aboundresources in this Chinese medicine composition, takes conveniently, makes the cost of this Chinese medicine composition lower, be more conducive to applying of this Chinese medicine composition.
In order to make this Chinese medicine composition to hormone-dependent tumor, especially the therapeutic effect of hormone-dependent breast cancer is better, the embodiment of the present invention additionally provides a kind of preferred Chinese medicine composition, comprises the composition of following weight portion: Radix Bupleuri 13-15 part, Radix Curcumae 9-18 part, Radix Astragali 7-18 part, Pericarpium Citri Reticulatae 3-15 part, Radix Salviae Miltiorrhizae 3-17 part, Resina garciniae 3-15 part, Cortex Moutan 2-12 part, Radix Glycyrrhizae 2-12 part, Flos Sophorae 2-12 part, Radix Arnebiae (Radix Lithospermi) 2-12 part, Spica Prunellae 2-12 part, Rhizoma Curcumae 2-12 part.
Particularly, the dosage form of above-mentioned Chinese medicine composition can elect tablet, capsule, pill, granule, Emulsion, ointment, spray, slow releasing preparation, Controlled release formulation or particles medication agents as, preferred particulates agent.
Particularly, the administering mode of this Chinese medicine composition can be the mode of drug administration by injection (such as, intravenous injection, articular cavity local injection or intramuscular injection etc.) or oral administration (such as oral or gavage).Preferred oral administering mode, 5-20g on the one, every day 1-3 time.The person that has regional glandular enlargement, dosage when every day, head took doubles.
Second aspect, embodiments provides a kind of medicine, comprises any one Chinese medicine composition above-mentioned for the treatment of effective dose.
Wherein, above-mentioned " treatment effective dose " refers to and produces the treatment function of hormone-dependent tumor or activity to human or animal, and can the amount that accepts by human or animal.
Be understandable that, this medicine also has treatment hormone-dependent tumor, especially the effect of hormone-dependent breast cancer, and side effect is less.
Further, this medicine can also comprise the other drug composition with above-mentioned Chinese medicine composition compatibility, and pharmaceutically acceptable carrier and/or adjuvant.
In the embodiment of the present invention, in order to improve the drug effect of this medicine or not affect this traditional Chinese medicine composition for treating hormone-dependent tumor, under the prerequisite of the especially drug effect of hormone-dependent breast cancer, give this Chinese medicine composition other drug effects, this medicine can also comprise the other drug composition with above-mentioned Chinese medicine composition compatibility." ingredient " herein can be Chinese medicine ingredients.
In addition, in order to improve this Chinese medicine composition take effect and patient take comfort level, and be convenient to be prepared into various form of Chinese drug, this Chinese medicine composition also comprises pharmaceutically acceptable carrier and/or adjuvant further.
Wherein, " pharmaceutically acceptable carrier and/or adjuvant " refers to and is applicable to human or animal and without excessive bad side reaction (as toxicity, stimulation and allergy), namely has carrier and/or the adjuvant of rational benefit/risk ratio.For example, this carrier can be capsule for medicine, liposome, cholesterol, chitosan etc.; This adjuvant can be dextrin and aspartame.
The third aspect, embodiments provides a kind of preparation method of Chinese medicine composition, comprises the following steps:
Step 101, Radix Bupleuri, Radix Salviae Miltiorrhizae, Resina garciniae, Pericarpium Citri Reticulatae, Flos Sophorae, Cortex Moutan, Radix Arnebiae (Radix Lithospermi), Radix Curcumae, Rhizoma Curcumae to be mixed and after pulverizing, obtain mixture, weight is utilized to be that the ethanol that this mixture weight 8-10 volume fraction is doubly 70-90% carries out extraction 2-3 time to this mixture, each 1-3h, obtains the first extracting solution and medicinal residues.
In step 101, the ethanol being 70-90% by use volume fraction, as extractant, improves the extraction ratio of above-mentioned Chinese medicine ingredients.Wherein, the extraction process described in the embodiment of the present invention is state of the art, and the embodiment of the present invention does not do concrete restriction to it at this.
Be understandable that, in the embodiment of the present invention, before each Chinese medicine ingredients of use prepares Chinese medicine composition, pretreatment need be carried out to each Chinese medicine ingredients, such as drying etc.
Making the complete stripping of the active substance in each Chinese medicine ingredients to be beneficial to, needing to carry out pulverization process to it,
Step 102, carry out concentrating under reduced pressure to this first extracting solution, obtain the first thick paste, the proportion of this first thick paste is 1.2-1.5.
Wherein, " concentrating under reduced pressure " described in the embodiment of the present invention is state of the art, and the embodiment of the present invention does not do concrete restriction to it at this.
Step 103, utilize that weight is medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae gross weight the mixture of 10-12 water doubly to above-mentioned medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae carry out extraction 2-3 time, each 1-1.5h, obtain the second extracting solution.
Step 104, carry out concentrating under reduced pressure to the second extracting solution, obtain the second thick paste, the proportion of this second thick paste is 1.2-1.5.
Step 105, by the first thick paste and described second thick paste mixing, and be processed into Chinese medicine preparation, obtain Chinese medicine composition.
In step 102 and 103, by the proportion of the first thick paste and the second thick paste is defined as 1.2-1.5, make the stability of the effective ingredient in each Chinese medicine ingredients the highest, the uniformity is the most consistent, the simplest and the most direct with follow-up adjuvant hybrid technique.
Wherein, step 101-102 and step 103-105 there is no the restriction of sequencing.
What the embodiment of the present invention provided above-mentionedly prepares in the method for Chinese medicine composition, and each composition mixes by following weight proportion: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
Particularly, step 105 also comprises: by the first thick paste and the second thick paste mixing, add dextrin and aspartame, mix homogeneously, using volume fraction be the ethanol of 85% as wetting agent, this Chinese medicine composition is processed into Chinese medicinal granule;
The weight ratio of this Chinese medicinal granule and aspartame is 1:0.008-0.012, preferred 1:0.1; The weight ratio of this Chinese medicinal granule and described dextrin is 1:0.7-1.2.
Be understandable that, the Chinese medicinal granule that this is prepared can also be processed further, be processed into electuary or capsule, so that the orally using of patient.
Fourth aspect, the embodiment of the present invention additionally provides a kind of preparation method preparing drops Chinese medicine composition, comprising:
Step 201, Radix Bupleuri, the Radix Astragali, Pericarpium Citri Reticulatae, Radix Salviae Miltiorrhizae, Resina garciniae, Cortex Moutan, Radix Glycyrrhizae, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) and Spica Prunellae mixed and carries out water boiling and precipitation with ethanol after pulverizing, obtaining the 3rd extracting solution.
Wherein, " water boiling and precipitation with ethanol " is state of the art, and the embodiment of the present invention does not do concrete restriction to it at this.
Step 202, Radix Curcumae, Rhizoma Curcumae mixed and extracts after pulverizing, obtaining volatile oil.
Wherein, the extraction process of traditional medicine volatile oil is also state of the art, and the embodiment of the present invention does not do concrete restriction to it at this.
Step 203, by the 3rd extracting solution and volatile oil mix homogeneously, and be processed into Chinese medicine preparation, obtain Chinese medicine composition;
The embodiment of the present invention provide this prepare in the method for the Chinese medicine composition of drops, each composition mixes by following weight proportion: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
Particularly, step 203 comprises: after the 3rd extracting solution and volatile oil mix homogeneously, utilize volume fraction be 5% propylene glycol carry out microemulsified, then utilize concentration be the soybean oil of 40% as outer oil phase, this Chinese medicine composition is processed into drop pill.
Below further the present invention will be described by specific embodiment.
Unreceipted condition person in following specific embodiment, all carries out according to this area normal condition.Agents useful for same or instrument unreceipted production firm person are can by commercially available conventional products.
Embodiment 1
Present embodiments provide a kind of Chinese medicine composition being used for the treatment of hormone-dependent tumor, comprise the composition of following weight portion: Radix Bupleuri 20 parts, Radix Curcumae 20 parts, the Radix Astragali 18 parts, Pericarpium Citri Reticulatae 17 parts, Radix Salviae Miltiorrhizae 16 parts, Resina garciniae 18 parts, Cortex Moutan 1 part, 3 parts, Radix Glycyrrhizae, 10 parts, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) 12 parts, Spica Prunellae 15 parts, Rhizoma Curcumae 8 parts.
This Chinese medicine composition is prepared by the following method:
According to the proportioning of above-mentioned each Chinese medicine ingredients, Radix Bupleuri, Radix Salviae Miltiorrhizae, Resina garciniae, Pericarpium Citri Reticulatae, Flos Sophorae, Cortex Moutan, Radix Arnebiae (Radix Lithospermi), Radix Curcumae, Rhizoma Curcumae to be mixed and after pulverizing, obtain mixture, weight is utilized to be the volume fraction of this mixture weight 10 times to be the ethanol of 80% to carry out extraction 3 times to this mixture, each 3h, obtains the first extracting solution and medicinal residues.Concentrating under reduced pressure is carried out to this first extracting solution, obtains the first thick paste that proportion is 1.4.Utilize that weight is medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae gross weight the mixture of the water of 12 times to above-mentioned medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae carry out extraction 2 times, each 1h, obtain the second extracting solution.Concentrating under reduced pressure is carried out to the second extracting solution, obtains the second thick paste that proportion is 1.2.By the first thick paste and described second thick paste mixing, add dextrin and aspartame, mix homogeneously, using volume fraction be the ethanol of 85% as wetting agent, this Chinese medicine composition is processed into Chinese medicinal granule.Wherein, the weight ratio of this Chinese medicinal granule and aspartame is 1:0.1; The weight ratio of this Chinese medicinal granule and dextrin is 1:0.7.
Embodiment 2
Present embodiments provide a kind of Chinese medicine composition being used for the treatment of hormone-dependent tumor, comprise the composition of following weight portion: Radix Bupleuri 14 parts, Radix Curcumae 17 parts, the Radix Astragali 7 parts, Pericarpium Citri Reticulatae 14 parts, Radix Salviae Miltiorrhizae 17 parts, Resina garciniae 10 parts, Cortex Moutan 11 parts, 10 parts, Radix Glycyrrhizae, 2 parts, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) 12 parts, Spica Prunellae 10 parts, Rhizoma Curcumae 10 parts.
This Chinese medicine composition is prepared by the following method:
According to the proportioning of above-mentioned each Chinese medicine ingredients, Radix Bupleuri, Radix Salviae Miltiorrhizae, Resina garciniae, Pericarpium Citri Reticulatae, Flos Sophorae, Cortex Moutan, Radix Arnebiae (Radix Lithospermi), Radix Curcumae, Rhizoma Curcumae to be mixed and after pulverizing, obtain mixture, weight is utilized to be the volume fraction of this mixture weight 8 times to be the ethanol of 70% to carry out extraction 2 times to this mixture, each 2h, obtains the first extracting solution and medicinal residues.Concentrating under reduced pressure is carried out to this first extracting solution, obtains the first thick paste that proportion is 1.5.Utilize that weight is medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae gross weight the mixture of the water of 10 times to above-mentioned medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae carry out extraction 3 times, each 1.5h, obtain the second extracting solution.Concentrating under reduced pressure is carried out to the second extracting solution, obtains the second thick paste that proportion is 1.3.By the first thick paste and described second thick paste mixing, add dextrin and aspartame, mix homogeneously, using volume fraction be the ethanol of 85% as wetting agent, this Chinese medicine composition is processed into Chinese medicinal granule.Wherein, the weight ratio of this Chinese medicinal granule and aspartame is 1:0.09; The weight ratio of this Chinese medicinal granule and dextrin is 1:1.2.
Embodiment 3
Present embodiments provide a kind of Chinese medicine composition being used for the treatment of hormone-dependent tumor, comprise the composition of following weight portion: Radix Bupleuri 13 parts, Radix Curcumae 9 parts, the Radix Astragali 18 parts, Pericarpium Citri Reticulatae 15 parts, Radix Salviae Miltiorrhizae 17 parts, Resina garciniae 8 parts, Cortex Moutan 2 parts, 2 parts, Radix Glycyrrhizae, 9 parts, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) 10 parts, Spica Prunellae 4 parts, Rhizoma Curcumae 9 parts.
This Chinese medicine composition is prepared by the following method:
According to the proportioning of above-mentioned each Chinese medicine ingredients, Radix Bupleuri, the Radix Astragali, Pericarpium Citri Reticulatae, Radix Salviae Miltiorrhizae, Resina garciniae, Cortex Moutan, Radix Glycyrrhizae, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) and Spica Prunellae mixed and carries out water boiling and precipitation with ethanol after pulverizing, obtaining extracting solution.Radix Curcumae, Rhizoma Curcumae mixed and extracts after pulverizing, obtaining volatile oil.After this extracting solution and volatile oil mix homogeneously, utilize volume fraction be 5% propylene glycol carry out microemulsified, then utilize concentration be the soybean oil of 40% as outer oil phase, this Chinese medicine composition is processed into drop pill.
Embodiment 4
The present embodiment has investigated the impact that Chinese medicine composition provided by the invention grows lotus human breast carcinoma MCF-7 nude mouse tumor, and concrete operations are as follows:
Get the female Balb/c nude mice of non-copulation (3-4 week age, 16-18g) 18, get two and do not do any process, be blank group; Then inoculate MCF-7 breast cancer cell by the left breast fat pad of residue 16 nude mices, tumor grows to 100-300mm 3shi Suiji divides 8 groups, is respectively model group and the 1st to the 7th experimental group.Wherein, blank group does not do any process; Model group presses 0.1ml (10g) -1dosage, the carboxymethyl cellulose (Carboxyl Methyl Cellulose, CMC) of gavage 0.1%, continuous 28 days; The Chinese medicine composition adopting embodiment 1 to provide carries out administration to the 1st to the 7th experimental group, and administering mode is by geometric ratio dosage (k=10 1/2≈ 3.16), be 0.152 ~ 152.288gkg by the extractum crude drug total of Chinese medicine composition -1(dosage as shown in table 1).Observe the situations such as nude mice spirit, diet and activity every day, weigh weekly 2 nude mice body weight and measure most major diameter (a)-transverse diameter (b) of subcutaneous transplantation tumor, calculating gross tumor volume V (mm 3)=1/6 π ab 2.Putting to death nude mice after 28 days, complete stripping subcutaneous tumors tuberosity, is the weight of the balance Fast Measurement tumor of 0.0001g by precision.Result is as shown in table 1:
Impact that table 1 various dose Qingdu granule grows nude mouse tumor ( n i=2)
As shown in Table 1, the Chinese medicine composition that the embodiment of the present invention provides has obvious inhibitory action to nude mice lotus human breast carcinoma, and its tumour inhibiting rate becomes positive correlation with dosage.
Embodiment 5
The MCF-7 Human Breast Cancer Cells that collection In vitro culture is in exponential phase makes single cell suspension, with 5 × 10 6the inoculum density of/200 μ l is inoculated in nude mice mammary fat pad.When gross tumor volume grows to about 100-300mm 3time, nude mice is divided into 4 groups at random by body weight and gross tumor volume equilibrium, often organizes 7, respectively administration every day 0.1ml10g -1.Get the nude mice of the non-inoculated tumour same period as blank group (non-inoculated tumour, administration 0.1%CMC); And the nude mice of these 4 groups of inoculated tumours is respectively model group (administration 0.1%CMC); Tamoxifen group (administration tamoxifen 5.6mgkg -1), Quercetin group (administration Quercetin 34.0mgkg -1) and Chinese medicine composition group (adopt the Chinese medicine composition that provides of the embodiment of the present invention 2 to carry out administration, dosage is 18gkg -1), above-mentioned each group of equal administration 28 days.Then statistical analysis is done to tumour inhibiting rate.
Result shows, compared with model group, gross tumor volume and the tumor quantity of the nude mice of tamoxifen group, Quercetin group and Chinese medicine composition group all show downward trend, wherein tumour inhibiting rate is respectively 38.52% (Chinese medicine composition group, P<0.01), 24.27% (Quercetin group, P<0.05) and 29.66% (tamoxifen group, P<0.01).
Visible, the Chinese medicine composition that the embodiment of the present invention provides has obvious inhibitory action for nude mice lotus human breast carcinoma, and its curative effect is better than tamoxifen.
From above-described embodiment, the angiogenesis that Chinese medicine composition provided by the invention can suppress mankind mastopathy cell to induce and immunologic escape.Chinese medicine composition of the present invention has the theoretical foundation that Chinese medical book is recorded, meet the Therapeutic Principle of the modern clinic traditional Chinese medical science, obtain the conclusion support of the clinical leading case of meta-analysis, clinical treatment relates to precancerous lesion, cancer related inflammation, cancer in situ, infiltrating carcinoma, the independent medication of metastatic carcinoma or the case verification of drug combination.
Embodiment 6
The mammary gland tissue of the present embodiment to the nude mice of blank group in embodiment 5, model group, tamoxifen group, Quercetin group and Chinese medicine composition group carries out hematoxylin-eosin staining (Hematoxylin-Eosin staining, HE dyes), then carry out under an optical microscope low (× 100), in (× 200), high power (× 400) object lens microphotograph, show structure and the cellular morphology of its linked groups.
Fig. 1 is the optical microscope figure of the mammary gland tissue after the HE dyeing of above-mentioned each group of nude mice.As shown in Figure 1, blank group mammary structure and cellular morphology normally, do not find obvious pathological changes.Breast cancer tissue's structure of model group inoculation growth is clear, and cancer nests sharpness of border size is more consistent, and without lumen of gland spline structure, cancerous cell arrangement is directionless nonpolarity; Blood capillary enriches, without significant interstitial fibers bundle; Belong to the typical structure of infiltrating duct carcinoma.Cancerous cell size and form is different, and pleomorphism is obvious, and endochylema enriches red dye, easily finds mitosis figures.Easily find degeneration, necrosis or the blood supply dependency secondary affection such as hemorrhage.Tamoxifen group inoculation breast cancer tissue's structure and cell size form are similar with model group; Blood supply dependency secondary affection is common.Quercetin group inoculation breast cancer tissue's structure and cell size form are similar with model group; Blood supply dependency secondary affection is common, and occurs that host glass sample becomes.Chinese medicine composition group: inoculation breast cancer tissue's structure and cell size form is similar with model group; Blood supply dependency secondary affection is common, and occurs that host glass sample becomes change.
Fig. 2 is the optical microscope figure of the uterine cancer cell after the HE dyeing of above-mentioned each group of nude mice.As shown in Figure 2, the uterine cancer cell structure of above-mentioned each group and cell size form are normal, without difference between remarkable group.
Fig. 3 is the optical microscope figure of the ovary tissue after the HE dyeing of above-mentioned each group of nude mice.As shown in Figure 3, above-mentioned each group of ovary tissue structure and cell size form are normal, without difference between remarkable group.
Embodiment 7
The present embodiment has investigated the expression of above-mentioned each group of nude mice carcinoma cell VEGF (VEGF) and VEGF R2 (VEGFR2) in embodiment 5 respectively, and result is as shown in table 2.Visible, compared with model group, the relative expression levels of the VEGFmRNA in the tumor tissues of tamoxifen group, Quercetin group and Chinese medicine composition group reduces 46.8% (P<0.05), 50.2% (P<0.01) and 42.2% (P<0.01) respectively.Which illustrating Chinese medicine composition provided by the invention by lowering VEGF gene expression, suppressing breast cancer tumour angiogenesis.
And, compared with model group, tamoxifen group, Quercetin group also reduce compared with model group with the VEGFR2mRNA relative expression levels in the tumor tissues of Chinese medicine composition group, reduce 35.0% (P<0.05), 41.0% (P<0.05) and 57.4% (P<0.01) respectively.Which illustrating Chinese medicine composition provided by the invention by lowering VEGFR2 gene expression, suppressing breast cancer tumour angiogenesis.
VEGF and VEGFR2mRNA relative expression levels in table 2 tumor tissues ( n i=7)
Compared with model group, ap<0.05, aap<0.01; Compared with tamoxifen, bp<0.05, bbp<0.01; Compared with Quercetin group, cp<0.05, ccp<0.01.
Embodiment 8
The Chinese medicine composition that the present embodiment utilizes embodiment 3 to provide, to mouse stomach, investigates the acute toxicity testing of this Chinese medicine composition: kunming mice is with maximum volume Chinese medicine composition gavage (20mLkg -1), administration maximum concentration is 3gmL -1, observe 1 week animal without death, zero difference between body weight and organ coefficient group.Illustrate that the anxious malicious maximum tolerated dose of mouse stomach administration is 60gkg -1above, its safety is higher.
Then, the Chinese medicine composition utilizing embodiment 3 to provide to the administration of SD rat oral gavage, to investigate the subacute toxicity of this Chinese medicine composition.Wherein, respectively gastric infusion 2 weeks (2.84gkg are carried out to rat by following Three doses -1, 9gkg -1, 28.4gkg -1), result shows rat non-toxic reaction, zero difference between body weight and organ coefficient group; The general form of system pathological observation 24 organ and organizational structure, without group difference, without pathological change.The Chinese medicine composition which illustrating the embodiment of the present invention provides is taken for 1 time and is repeatedly taken without obvious acute toxicity and cumulative toxicity.Its safety is higher, and side effect is lower, has higher safe handling.
The foregoing is only preferred embodiment of the present invention, not in order to limit the scope of the invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.

Claims (10)

1. be used for the treatment of a Chinese medicine composition for hormone-dependent tumor, comprise the composition of following weight portion: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
2. Chinese medicine composition according to claim 1, it is characterized in that, described Chinese medicine composition comprises the composition of following weight portion: Radix Bupleuri 13-15 part, Radix Curcumae 9-18 part, Radix Astragali 7-18 part, Pericarpium Citri Reticulatae 3-15 part, Radix Salviae Miltiorrhizae 3-17 part, Resina garciniae 3-15 part, Cortex Moutan 2-12 part, Radix Glycyrrhizae 2-12 part, Flos Sophorae 2-12 part, Radix Arnebiae (Radix Lithospermi) 2-12 part, Spica Prunellae 2-12 part, Rhizoma Curcumae 2-12 part.
3. Chinese medicine composition according to claim 1 and 2, is characterized in that, the dosage form of described Chinese medicine composition elects tablet, capsule, pill, granule, Emulsion, ointment, spray, slow releasing preparation, Controlled release formulation or particles medication agents as.
4. a medicine, comprises the Chinese medicine composition described in any one of claim 1-3 for the treatment of effective dose.
5. medicine according to claim 4, is characterized in that, described medicine also comprises the other drug composition with described Chinese medicine composition compatibility, and pharmaceutically acceptable carrier and/or adjuvant.
6. medicine according to claim 5, is characterized in that, described adjuvant is dextrin and aspartame.
7. a preparation method for Chinese medicine composition according to claim 1, comprising:
Step a, Radix Bupleuri, Radix Salviae Miltiorrhizae, Resina garciniae, Pericarpium Citri Reticulatae, Flos Sophorae, Cortex Moutan, Radix Arnebiae (Radix Lithospermi), Radix Curcumae, Rhizoma Curcumae to be mixed and after pulverizing, obtain mixture, weight is utilized to be that the ethanol that described mixture weight 8-10 volume fraction is doubly 70-90% carries out extraction 2-3 time to described mixture, each 1-3h, obtains the first extracting solution and medicinal residues;
Step b, carry out concentrating under reduced pressure to described first extracting solution, obtain the first thick paste, the proportion of described first thick paste is 1.2-1.5;
Step c, utilize weight to be described medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae gross weight the mixture of 10-12 water doubly to described medicinal residues, the Radix Astragali, Radix Glycyrrhizae and Spica Prunellae carry out extraction 2-3 time, each 1-1.5h, obtain the second extracting solution;
Steps d, carry out concentrating under reduced pressure to described second extracting solution, obtain the second thick paste, the proportion of described second thick paste is 1.2-1.5;
Step e, by described first thick paste and described second thick paste mixing, and be processed into Chinese medicine preparation, obtain described Chinese medicine composition;
In described Chinese medicine composition, the weight proportion of each composition is: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
8. method according to claim 7, is characterized in that, described step e comprises: by described first thick paste and described second thick paste mixing, add dextrin and aspartame, mix homogeneously, using volume fraction be the ethanol of 85% as wetting agent, described Chinese medicine composition is processed into Chinese medicinal granule;
The weight ratio of described Chinese medicinal granule and described aspartame is 1:0.008-0.012;
The weight ratio of described Chinese medicinal granule and described dextrin is 1:0.7-1.2.
9. a preparation method for Chinese medicine composition according to claim 1, comprising:
Step α, Radix Bupleuri, the Radix Astragali, Pericarpium Citri Reticulatae, Radix Salviae Miltiorrhizae, Resina garciniae, Cortex Moutan, Radix Glycyrrhizae, Flos Sophorae, Radix Arnebiae (Radix Lithospermi) and Spica Prunellae mixed and carries out water boiling and precipitation with ethanol after pulverizing, obtaining the 3rd extracting solution;
Step β, Radix Curcumae, Rhizoma Curcumae mixed and extracts after pulverizing, obtaining volatile oil;
Step γ, by described 3rd extracting solution and described volatile oil mix homogeneously, and be processed into Chinese medicine preparation, obtain described Chinese medicine composition;
In described Chinese medicine composition, the weight proportion of each composition is: Radix Bupleuri 8-20 part, Radix Curcumae 4-23 part, Radix Astragali 2-23 part, Pericarpium Citri Reticulatae 1-18 part, Radix Salviae Miltiorrhizae 1-20 part, Resina garciniae 1-18 part, Cortex Moutan 1-17 part, Radix Glycyrrhizae 1-17 part, Flos Sophorae 1-17 part, Radix Arnebiae (Radix Lithospermi) 1-17 part, Spica Prunellae 1-17 part, Rhizoma Curcumae 1-17 part.
10. method according to claim 9, it is characterized in that, described step γ comprises: after described 3rd extracting solution and described volatile oil mix homogeneously, utilize volume fraction be 5% propylene glycol carry out microemulsified, then utilize concentration be the soybean oil of 40% as outer oil phase, described Chinese medicine composition is processed into drop pill.
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