CN118001343A - Preparation method of breast cancer resistant traditional Chinese medicine compound - Google Patents
Preparation method of breast cancer resistant traditional Chinese medicine compound Download PDFInfo
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Abstract
The invention discloses a preparation process of a traditional Chinese medicine compound for resisting breast cancer growth, which selects codonopsis pilosula, bupleurum, white paeony root, semen akebiae, indian iphigenia bulb, snakegourd peel, seaweed, fritillaria thunbergii, honeycomb, spina gleditsiae and guangdong seed as raw material formulas and prepares an oral preparation with common auxiliary materials of medicines. The traditional Chinese medicine compound can inhibit the growth of breast cancer, and has synergistic and toxicity-reducing effects by combining with a chemotherapeutic drug 5-fluorouracil.
Description
Technical Field
The invention relates to a preparation method of a traditional Chinese medicine compound for resisting breast cancer, belonging to the field of traditional Chinese medicines.
Background
Breast cancer is one of the common malignant tumors of women, 130 tens of thousands of new cases of breast cancer occur annually in the global scope, and more than 50 tens of thousands of people die due to breast cancer. Chemotherapy is the primary means of treating breast cancer, and can be used at various treatment sites during breast cancer treatment, and patients can receive chemotherapy before/after surgery, or as an adjunct to another therapy. Chemotherapy is often associated with side effects because it kills rapidly growing and isolated cells, including cancer cells and normal growing healthy cells.
Research shows that the advantages of multiple genes, multiple targets and low toxic and side effects of the traditional Chinese medicine are more and more obvious. The traditional Chinese medicine is used for maintaining chemotherapy, so that the treatment effect can be improved, the toxic effects of various chemotherapeutic drugs can be obviously reduced, and the survival rate of tumor patients can be improved. The 5-fluorouracil can inhibit thymine nucleotide synthetase, block the conversion of deoxypyrimidine nucleotide into thymine nucleotide, interfere DNA and RNA synthesis, is an atypical cell cycle specific chemotherapeutic drug, mainly acts on S phase and also acts on cells in other phases. However, due to the effects of tumor and individual heterogeneity, some patients remain insensitive to the drug or develop severe lethal toxic reactions. In clinical application, the adverse reactions such as gastrointestinal reaction and bone marrow suppression are relieved by limiting the dosage of the medicine, changing the administration route or selecting auxiliary medicines. In recent years, many researches on the combined application of traditional Chinese medicines and 5-fluorouracil have been reported, and the related prescription medicines are suggested to have the effects of improving the tumor inhibiting effect of 5-fluorouracil, improving the immune function and relieving the bone marrow inhibition.
Aiming at a breast cancer patient with liver depression and stasis, the invention selects the prescription taking liver soothing and stasis removing as the treatment rules, and selects the raw material prescription of pilose asiabell root, bupleurum, white paeony root, semen akebiae, indian iphigenia bulb, snakegourd peel, seaweed, thunberg fritillary bulb, honeycomb, spina gleditsiae and guangdong seed, so as to prepare the traditional Chinese medicine compound for resisting the growth of breast cancer, and the traditional Chinese medicine compound can play the effects of synergism and toxicity reduction when being used together with the chemotherapeutic medicine 5-fluorouracil.
The Chinese patent publication No. CN105727161A discloses a Chinese medicinal preparation for treating breast cancer and a preparation method thereof, which discloses a compound Chinese medicinal composition for treating breast cancer, and does not mention whether the Chinese medicinal composition can be combined with a chemotherapeutic medicine for treating breast cancer. The Chinese patent publication CN109248209A discloses a Chinese medicinal composition for resisting breast cancer, a Chinese medicinal preparation and a preparation method thereof, and discloses a Chinese medicinal composition for resisting breast cancer and a preparation method thereof, which can effectively kill breast cancer cells and can not be used in combination with chemotherapeutics to improve the effect of treating breast cancer.
Disclosure of Invention
The invention aims to provide a preparation method of a traditional Chinese medicine compound for resisting breast cancer growth, which has a good effect on inhibiting breast cancer growth through reasonable proportion and synergistic effect of the medicinal materials under the guidance of the theory of traditional Chinese medicine. The breast cancer is treated by combining the traditional Chinese medicine compound with the 5-fluorouracil, the advantages of dialectical treatment of the traditional Chinese medicine are fully exerted, the treatment effect of the medicine can be improved, the occurrence of serious toxic and side effects of chemotherapy can be also improved, and the sensitivity, the clinical good conversion rate and the life quality of tumor patients of the chemotherapeutic medicine are improved.
The traditional Chinese medicine compound for resisting breast cancer growth disclosed by the invention is prepared by combining radix codonopsis, radix bupleuri, radix paeoniae alba, semen akebiae, indian iphigenia bulb, pericarpium trichosanthis, seaweed, fritillaria thunbergii, nidus vespae, spina gleditsiae and semen vaccariae. Modern researches have shown that the above-mentioned herbs have effects of invigorating qi, promoting blood circulation, resisting tumor, etc., and the common combination has effects of dispersing stagnated liver qi, dispelling blood stasis, and resisting breast cancer.
The invention is characterized in that: the traditional Chinese medicine composition is a prescription selected by taking liver soothing and stasis dispelling as treatment rules aiming at breast cancer patients with liver depression and stasis, and has good effect on inhibiting breast cancer growth.
The raw materials for preparing the active components of the medicine of the invention are as follows: 10-60 parts of radix codonopsis pilosulae, 5-30 parts of radix bupleuri, 5-30 parts of white peony root, 5-30 parts of semen akebiae, 5-30 parts of Indian iphigenia bulb, 5-30 parts of snakegourd peel, 5-30 parts of seaweed, 10-60 parts of fritillaria thunbergii, 5-30 parts of honeycomb, 5-30 parts of spina gleditsiae and 10-60 parts of guangdong seed. Preferably 30 parts of radix codonopsis pilosulae, 15 parts of radix bupleuri, 15 parts of white peony root, 15 parts of semen akebiae, 15 parts of Indian iphigenia bulb, 15 parts of snakegourd peel, 15 parts of seaweed, 30 parts of fritillary bulb, 15 parts of honeycomb, 15 parts of spina gleditsiae and 30 parts of guangdong semen vaccariae.
The medicine of the invention can be prepared into conventional oral preparations such as oral liquid, granules, decoction and the like by adopting a conventional method of a traditional Chinese medicine preparation.
Mixing radix Codonopsis, bupleuri radix, radix Paeoniae alba, semen Aristolochiae, pseudobulbus Cremastrae seu pleiones, pericarpium Trichosanthis, sargassum, bulbus Fritillariae Thunbergii, nidus Vespae, spina Gleditsiae and semen Vaccariae at the above weight ratio, soaking in 8-12 times of water for 1-2 hr, preferably 10 times of water for 1.5 hr, decocting for 10-30 min, preferably 20 min, filtering under normal pressure, and collecting filtrate; adding 6-10 times of water, preferably 8 times of water into the filter residue, decocting for 10-20 minutes, preferably 15 minutes, filtering under normal pressure, and collecting filtrate; adding 4-8 times of water, preferably 6 times of water into the filter residue, decocting for 5-15 min, preferably 10 min, filtering under normal pressure, and collecting filtrate. Mixing the three filtrates, evaporating and concentrating to obtain extract, baking at 80deg.C in oven, and pulverizing into fine powder. The fine powder can be added with various conventional adjuvants, sweeteners, antiseptic, etc. required for preparing different dosage forms to prepare common Chinese medicinal preparation dosage forms such as oral liquid, granule, decoction, etc.
The invention is further illustrated below with reference to examples.
Drawings
In order that the invention may be more readily understood, a more particular description of the invention will be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings, in which
FIG. 1 is a diagram showing a test for the change in constitution of a mouse;
FIG. 2 is a graph showing the change in tumor volume of mice;
fig. 3 is a chart of tumor suppression rate test.
EXAMPLE 1 preparation of the oral liquid of the invention (taking ten times of raw materials as an example)
1. Weighing the following raw materials in parts by weight: 300 parts of radix codonopsis, 150 parts of radix bupleuri, 150 parts of white peony root, 150 parts of semen akebiae, 150 parts of Indian iphigenia bulb, 150 parts of snakegourd peel, 150 parts of seaweed, 300 parts of fritillaria thunbergii, 150 parts of honeycomb, 150 parts of spina gleditsiae and 300 parts of guangdong semen vaccariae.
2. Soaking radix Codonopsis, bupleuri radix, radix Paeoniae alba, semen Pittospori Glabrati, pseudobulbus Cremastrae seu pleiones, pericarpium Trichosanthis, sargassum, bulbus Fritillariae Thunbergii, nidus Vespae, spina Gleditsiae and semen Vaccariae in 10 times of water for 1.5 hr, decocting for 20min, filtering under normal pressure, and collecting filtrate; adding 8 times of water into filter residues, decocting for 15 minutes, filtering at normal pressure, and collecting filtrate; adding 6 times of water into the filter residue, and decocting for 10 minutes. Mixing the three filtrates, evaporating and concentrating to obtain extract, baking at 80deg.C in oven, and pulverizing into fine powder.
3. Soaking the above fine powder in boiling water, adding sweetener and antiseptic, removing residues to obtain juice, mixing, and packaging in sterile clean dry container.
EXAMPLE 2 preparation of the granules of the invention (taking ten times the raw material ratio as an example)
1. Weighing the following raw materials in parts by weight: 300 parts of radix codonopsis, 150 parts of radix bupleuri, 150 parts of white peony root, 150 parts of semen akebiae, 150 parts of Indian iphigenia bulb, 150 parts of snakegourd peel, 150 parts of seaweed, 300 parts of fritillaria thunbergii, 150 parts of honeycomb, 150 parts of spina gleditsiae and 300 parts of guangdong semen vaccariae.
2. Soaking radix Codonopsis, bupleuri radix, radix Paeoniae alba, semen Pittospori Glabrati, pseudobulbus Cremastrae seu pleiones, pericarpium Trichosanthis, sargassum, bulbus Fritillariae Thunbergii, nidus Vespae, spina Gleditsiae and semen Vaccariae in 10 times of water for 1.5 hr, decocting for 20min, filtering under normal pressure, and collecting filtrate; adding 8 times of water into filter residues, decocting for 15 minutes, filtering at normal pressure, and collecting filtrate; adding 6 times of water into the filter residue, and decocting for 10 minutes. Mixing the three filtrates, evaporating and concentrating to obtain extract, baking at 80deg.C in oven, and pulverizing into fine powder.
3. Adding appropriate amount of sugar powder and other adjuvants (starch, rhizoma Dioscoreae powder, dextrin, etc.), stirring, sieving with 10-12 mesh sieve, drying, and sieving with 8-14 mesh sieve.
EXAMPLE 3 preparation of the decoction of the invention (taking ten times the raw materials as an example)
1. Weighing the following raw materials in parts by weight: 300 parts of radix codonopsis, 150 parts of radix bupleuri, 150 parts of white peony root, 150 parts of semen akebiae, 150 parts of Indian iphigenia bulb, 150 parts of snakegourd peel, 150 parts of seaweed, 300 parts of fritillaria thunbergii, 150 parts of honeycomb, 150 parts of spina gleditsiae and 300 parts of guangdong semen vaccariae.
2. Soaking radix Codonopsis, bupleuri radix, radix Paeoniae alba, semen Pittospori Glabrati, pseudobulbus Cremastrae seu pleiones, pericarpium Trichosanthis, sargassum, bulbus Fritillariae Thunbergii, nidus Vespae, spina Gleditsiae and semen Vaccariae in 10 times of water for 1.5 hr, decocting for 20min, filtering under normal pressure, and collecting filtrate; adding 8 times of water into filter residues, decocting for 15 minutes, filtering at normal pressure, and collecting filtrate; adding 6 times of water into the filter residue, and decocting for 10 minutes. Mixing the three filtrates, evaporating and concentrating to obtain extract, baking at 80deg.C in oven, and pulverizing into fine powder.
3. Soaking the above fine powder in boiling water, removing residues, collecting juice, and mixing.
Experimental example 1 influence of the combination of 5-fluorouracil on tumor quality and volume of tumor-bearing mice with 4T1 breast cancer
(1) Tumor model construction
After 4T1 cell passage number weeks, cells in logarithmic growth phase were collected by pancreatin digestion, counted, resuspended in matrigel: pbs=1:1 ratio mixture, and the final concentration was adjusted to 1×10 7 cells/mL. And (3) preparing, transporting and taking the matrigel-containing liquid in the ice box in the whole process to prevent matrigel from solidifying.
After the mice are sterilized by alcohol, 200 mu L (containing 2X 10 6 cells) of cell suspension is taken by a 0.45X 16mm 1mL injector to be injected into the right armpit side of the mice, and experiments prove that the method can successfully construct a breast cancer tumor-bearing mouse model, and the success rate can reach more than 90 percent. The mice were vaccinated 3 days after tumor cells.
(2) Grouping and administration
70 Mice were randomly divided into 7 groups: normal group, model group, 5-fluorouracil (5-FU) group, chinese medicinal compound group, low-dose Chinese medicinal compound +5-FU, medium-dose Chinese medicinal compound +5-FU, and high-dose Chinese medicinal compound +5-FU.5-FU was administered by intraperitoneal injection at a dose of 30mg/kg body weight/day. Decocting 210g of the traditional Chinese medicine compound prescription drug of the invention into water decoction, and concentrating to 210mL, wherein the concentration of the extract is regarded as 1g/mL. The Chinese herbal medicine compound of the invention is singly administered by adopting a gastric lavage mode according to the medium dose of 30g/kg body weight/day dose. The low, medium and high doses of the traditional Chinese medicine compound in the combined administration group are respectively administered according to the dosage of 15 g/kg body weight/day, 30g/kg body weight/day by adopting a stomach irrigation mode. The experimental period was 15 days, and the body mass and tumor volume of the mice were recorded every 2 days, and the tumor volume was calculated using the formula v=0.5×a×b 2, where a represents the long diameter and b represents the short diameter.
Table 1 and FIG. 1 show that the quality of mice is slowly increased; table 2 and FIG. 2 show that the tumor volume change of mice, when the compound traditional Chinese medicine is combined with 5-FU, the tumor mass and volume of the mice with tumor of experimental end point 4T1 breast cancer gradually decrease along with the increase of the compound traditional Chinese medicine dosage compared with the single use of 5-FU, but the data of low dosage and medium dosage have no statistical significance (p is more than 0.05), and the high dosage has significant difference (p is less than 0.05). The inhibition effect of the combination of the low, medium and high doses of the traditional Chinese medicine compound and 5-FU has a gradually increasing trend, but the data of the traditional Chinese medicine compound have no statistical significance (p is more than 0.05). The result shows that the combination of the traditional Chinese medicine compound and the chemotherapeutic drug 5-fluorouracil can effectively inhibit the tumor quality and volume of the tumor-bearing mice with 4T1 breast cancer, and the curative effect of the combination of the high-dose traditional Chinese medicine compound and the 5-fluorouracil is best.
TABLE 1 variation in body constitution of mice before and after administrationn＝10)
Note that: p < 0.05, < p < 0.01, < p < 0.001, compared to the control group.
TABLE 2 tumor volume changes in mice before and after dosingn＝10)
Note that: p < 0.05, < p < 0.01, < p < 0.001, compared to the control group. # p < 0.05 compared to the 5-FU group, RJF-L+5-FU group.
Experimental example 2 influence of the combination of 5-fluorouracil on tumor suppression Rate of 4T1 breast cancer tumor-bearing mice
(1) Tumor model construction
After 4T1 cell passage number weeks, cells in logarithmic growth phase were collected by pancreatin digestion, counted, resuspended in matrigel: pbs=1:1 ratio mixture, and the final concentration was adjusted to 1×10 7 cells/mL. And (3) preparing, transporting and taking the matrigel-containing liquid in the ice box in the whole process to prevent matrigel from solidifying.
After the mice are sterilized by alcohol, 200 mu L (containing 2X 10 6 cells) of cell suspension is taken by a 0.45X 16mm 1mL injector to be injected into the right armpit side of the mice, and experiments prove that the method can successfully construct a breast cancer tumor-bearing mouse model, and the success rate can reach more than 90 percent. The mice were vaccinated 3 days after tumor cells.
(2) Grouping and administration
70 Mice were randomly divided into 7 groups: normal group, model group, 5-fluorouracil (5-FU) group, chinese medicinal compound decoction, low-dose Chinese medicinal compound +5-FU, medium-dose Chinese medicinal compound +5-FU, and high-dose Chinese medicinal compound +5-FU.5-FU was administered by intraperitoneal injection at a dose of 30mg/kg body weight/day. Decocting 210g of the traditional Chinese medicine compound prescription drug of the invention into water decoction, and concentrating to 210mL, wherein the concentration of the extract is regarded as 1g/mL. The Chinese herbal medicine compound of the invention is singly administered by adopting a gastric lavage mode according to the medium dose of 30g/kg body weight/day dose. The low, medium and high doses of the traditional Chinese medicine compound in the combined administration group are respectively administered according to the dosage of 15 g/kg body weight/day, 30g/kg body weight/day by adopting a stomach irrigation mode. Mice were sacrificed on day 15 and tumor mass was removed to calculate mass and tumor inhibition rate.
Table 3 and FIG. 3 show that each group has obvious inhibition effect (p < 0.001) on tumor growth of 4T1 breast cancer tumor-bearing mice by 5-FU, chinese herbal compound, low-dose Chinese herbal compound +5-FU, medium-dose Chinese herbal compound +5-FU and high-dose Chinese herbal compound +5-FU, compared with the model group, wherein the inhibition effect of single use of Chinese herbal compound water decoction is weakest, the inhibition effect is only 25.78%, the inhibition effect of high-dose Chinese herbal compound +5-FU is strongest, and the inhibition rate is 72.66%. Compared with the single use of 5-FU or traditional Chinese medicine compound, the tumor inhibition rate is obviously increased when the traditional Chinese medicine compound is combined with 5-FU, and the data has obvious difference (p is less than 0.05). The result shows that the combination of the traditional Chinese medicine compound and the chemotherapeutic 5-fluorouracil can inhibit the tumor growth of the tumor-bearing mice with 4T1 breast cancer, and the high-dose traditional Chinese medicine compound can effectively improve the tumor inhibition rate of the 5-fluorouracil.
TABLE 3 mass of each tumor mass and tumor inhibition rate at the end of the experimentn＝10)
Note that: tumor inhibition rate = (control-treatment-mass average)/control-mass average 100 or (control-mass-treatment-mass)/control-mass average 100/n. P < 0.05, < p < 0.01, < p < 0.001, compared to the control group. # p < 0.05 compared to the 5-FU group.
Claims (4)
1. A preparation method of a traditional Chinese medicine compound for resisting breast cancer growth is characterized in that aiming at a breast cancer patient with liver depression and stasis, a prescription is selected by taking liver soothing and stasis dispelling as treatment rules, and a traditional Chinese medicine preparation is prepared by the prescription and corresponding auxiliary materials.
2. The compound Chinese medicine according to claim 1, wherein the composition comprises radix codonopsis pilosulae 10-60 parts, radix bupleuri 5-30 parts, radix paeoniae alba 5-30 parts, semen akebiae 5-30 parts, edible tulip 5-30 parts, snakegourd peel 5-30 parts, seaweed 5-30 parts, fritillaria thunbergii 10-60 parts, nidus vespae 5-30 parts, spina gleditsiae 5-30 parts and guangdong seed 10-60 parts. Preferably 30 parts of radix codonopsis pilosulae, 15 parts of radix bupleuri, 15 parts of white peony root, 15 parts of semen akebiae, 15 parts of Indian iphigenia bulb, 15 parts of snakegourd peel, 15 parts of seaweed, 30 parts of fritillaria thunbergii, 15 parts of honeycomb, 15 parts of spina gleditsiae and 30 parts of guangdong semen vaccariae.
3. The preparation method of the traditional Chinese medicine compound combination according to claim 1 and 2, comprising the following steps:
(1) Mixing radix Codonopsis, bupleuri radix, radix Paeoniae alba, semen Aristolochiae, pseudobulbus Cremastrae seu pleiones, pericarpium Trichosanthis, sargassum, bulbus Fritillariae Thunbergii, nidus Vespae, spina Gleditsiae and semen Vaccariae at the above weight ratio, soaking in 8-12 times of water for 1-2 hr, preferably 10 times of water for 1.5 hr, decocting for 10-30 min, preferably 20min, filtering under normal pressure, and collecting filtrate; adding 6-10 times of water, preferably 8 times of water into the filter residue, decocting for 10-20 minutes, preferably 15 minutes, filtering under normal pressure, and collecting filtrate; adding 4-8 times of water, preferably 6 times of water into the filter residue, decocting for 5-15 min, preferably 10 min, filtering under normal pressure, and collecting filtrate.
(2) Mixing the three filtrates, evaporating, concentrating, and making into extract.
(3) Baking the extract in oven at 80deg.C until it is completely dried, and pulverizing into fine powder.
(4) The above fine powder can be added with conventional adjuvants, sweetener, antiseptic, etc. required for preparing different dosage forms, and made into common Chinese medicinal preparation dosage forms such as oral liquid, granule, decoction, etc.
4. The use of the Chinese medicinal composition as claimed in claim 1 or 2 for preparing a medicament having an anti-breast cancer growth effect.
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