A pharmaceutical composition and its application in anti-tumor drugs and products

Abstract

This invention provides a pharmaceutical composition and its application in antitumor drugs, belonging to the technical field of traditional Chinese medicine compositions. The pharmaceutical composition provided by this invention includes rhubarb, turmeric, *Eriocaulon buergerianum*, asafoetida, costus root, clove, chebula, and cordyceps sinensis processed through specific steps. The rhubarb is obtained by slicing, processing with alcohol, stir-frying, pulverizing, and sieving; the turmeric is obtained by slicing, processing with alcohol, and stir-frying; the *Eriocaulon buergerianum* is obtained by processing with alcohol, stir-frying, vinegar, stir-frying, pulverizing, and sieving; the asafoetida is obtained by cutting into pieces and processing with alcohol; the costus root is obtained by slicing and processing with alcohol; and the clove is obtained by stir-frying, pulverizing, and sieving. The pharmaceutical composition provided by this invention can significantly inhibit the in vitro survival rate of HepG2 cells and effectively improve tumor volume and serum tumor markers AFP and TSGF levels in hepatocellular carcinoma mice, providing a promising prospect for the preparation of antitumor drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine compositions, and in particular relates to a medicine composition and its application in anti-tumor medicine and products. Background Art

[0002] Hepatocellular carcinoma is one of the malignant tumors with high morbidity and mortality worldwide. Although modern medicine has made certain progress in surgery, radiotherapy, chemotherapy, etc., no matter which treatment method is used, it has certain limitations and is far from achieving the ideal therapeutic effect. Therefore, more effective treatment methods and therapeutic drugs need to be developed.

[0003] Using traditional Chinese medicine to treat tumors is a unique treatment method in my country and has a long history. Compared with other drugs, Chinese medicine has very unique advantages in treating tumors, such as mild medicinal properties, which will not cause great pain to patients during treatment; comprehensive effects, which help to improve patients' resistance and prolong their life; less prone to recurrence after recovery and less toxic side effects. Chinese herbal medicine contains a variety of plant monomers with strong anti-tumor effects, which provides new ideas and methods for finding new anti-cancer drugs. However, how to separate and extract them and develop and utilize them reasonably is a difficult problem.

[0004] Chinese medicine processing is a pharmaceutical technology adopted according to the theory of traditional Chinese medicine, the needs of dialectical treatment and the properties of the medicine itself, and the different requirements of the preparation. At present, there are few studies on the processing technology of rhubarb, turmeric, nine-scented worm, asafoetida, costus root, clove drug combination, terminalia chebula and cordyceps sinensis. Therefore, providing a processed Chinese medicine composition has broad prospects in the treatment of tumors. Summary of the invention

[0005] In view of the above shortcomings, the present invention provides a pharmaceutical composition and its application and product in anti-tumor drugs. The pharmaceutical composition provided by the present invention comprises rhubarb, turmeric, schisandra, asafoetida, costus root, clove, terminalia chebula and cordyceps sinensis processed by specific steps. The rhubarb is obtained by slicing, making wine, frying, crushing and sieving; the turmeric is obtained by slicing, making wine, and frying; the schisandra is obtained by making wine, frying, vinegar, frying, crushing and sieving; the asafoetida is obtained by dicing and making wine; the costus root is obtained by slicing and making wine; the clove is obtained by frying, crushing and sieving. The pharmaceutical composition provided by the present invention can significantly inhibit the in vitro survival rate of HepG2 cells, can effectively improve the tumor volume and serum tumor markers AFP and TSGF levels of mice with hepatocellular carcinoma, and provides a good development prospect for the preparation of anti-tumor drugs.

[0006] The technical solution of the present invention is:

[0007] In one aspect, the present invention provides a pharmaceutical composition comprising rhubarb, turmeric, schisandra chinensis, asafoetida, costusroot, clove, terminalia chebula and cordyceps sinensis.

[0008] Specifically, the pharmaceutical composition comprises, by weight, 150-200 parts of rhubarb, 150-200 parts of turmeric, 112-150 parts of nine-scented insects, 75-100 parts of asafoetida, 75-100 parts of costusroot, 75-100 parts of cloves, 95-130 parts of terminalia chebula and 15-20 parts of cordyceps.

[0009] Preferably, the pharmaceutical composition comprises, by weight, 180 parts of rhubarb, 180 parts of turmeric, 135 parts of scutellaria baicalensis, 90 parts of asafoetida, 90 parts of costusroot, 90 parts of cloves, 117 parts of terminalia chebula and 18 parts of cordyceps.

[0010] Specifically, the preparation method of rhubarb, turmeric, nine-scented worm, asafoetida, costusroot, clove, terminalia chebula and cordyceps is as follows:

[0011] The rhubarb preparation method comprises: slicing the rhubarb, making with wine, frying, crushing and screening;

[0012] The turmeric processing method includes: slicing turmeric, making with wine, and frying;

[0013] The processing method of the nine-scented worm includes: making the nine-scented worm with wine, frying, making vinegar, frying, crushing and sieving;

[0014] The processing method of asafoetida comprises: cutting asafoetida into pieces and making with wine;

[0015] The processing method of costus root comprises: cutting costus root into slices and making with wine;

[0016] The processing method of cloves comprises: frying, crushing and screening the cloves.

[0017] Preferably, in the method for preparing rhubarb, the wine used for the wine making is rice wine, and the weight ratio of the rhubarb slices to the rice wine is 10-12:1.

[0018] Further preferably, in the method for preparing rhubarb, the weight ratio of the rhubarb slices to the rice wine is 12:1.

[0019] Preferably, in the method for processing rhubarb, the frying is performed at 180-200° C. for 10-15 min.

[0020] Further preferably, in the method for processing rhubarb, the frying is performed at 180° C. for 15 minutes.

[0021] Preferably, in the method for preparing rhubarb, the crushing and screening is crushing through an 80-mesh sieve.

[0022] Further preferably, the processing method of the rhubarb is as follows: remove impurities from the rhubarb, wash, slice, dry, and sieve out debris to obtain rhubarb slices. Add yellow wine to the rhubarb slices at a weight ratio of 12:1 to make them moist. After the yellow wine is completely absorbed, stir-fry at 180°C for 15 minutes. Crush and pass through an 80-mesh sieve to obtain the processed rhubarb.

[0023] Preferably, in the turmeric processing method, the wine used in the wine making is yellow rice wine, and the weight ratio of the turmeric slices to the yellow rice wine is 3-5:1.

[0024] Further preferably, in the turmeric processing method, the weight ratio of the turmeric slices to the rice wine is 5:1.

[0025] Preferably, in the processing method of turmeric, the frying is performed at 120-150° C. for 15-20 min.

[0026] Further preferably, in the turmeric processing method, the frying is frying at 120° C. for 20 minutes.

[0027] Further preferably, the processing method of the turmeric is: pick out impurities, wash, add 25°C water to cover the medicinal materials, soak for 1 hour, put into a basket to drain the water, transfer to a jar, cover and soak, soak thoroughly, take out, slice, dry in the sun, and obtain turmeric slices. Add yellow wine at a weight ratio of turmeric slices: yellow wine = 3:1, stir-fry at 120°C for 20 minutes, and obtain the processed turmeric.

[0028] Preferably, the method for preparing the nine-scented insect comprises: mixing the nine-scented insect with rice wine, steaming, frying after the rice wine is completely absorbed, adding rice vinegar, continuing to fry, and crushing and sieving.

[0029] Further preferably, the weight ratio of the nine-scented insects to rice wine is 10-12:1, and the weight ratio of the nine-scented insects to rice vinegar is 5-10:1.

[0030] Still more preferably, the weight ratio of the nine-scented insects to rice wine is 12:1, and the weight ratio of the nine-scented insects to rice vinegar is 10:1.

[0031] More preferably, the frying is performed at 180-200° C. for 8-10 min, and the continued frying is performed at 120-150° C. for 15-20 min.

[0032] Still more preferably, the frying is frying at 180° C. for 10 min, and the continued frying is frying at 150° C. for 15 min.

[0033] Further preferably, the crushing and screening is crushing through an 80-mesh sieve.

[0034] More preferably, the processing method of the nine-scented insect is as follows: according to the weight ratio of nine-scented insect to rice wine = 12:1, add rice wine to the nine-scented insect, mix well, and steam. After the rice wine is completely absorbed, stir-fry at 180°C for 10 minutes. According to the weight ratio of nine-scented insect to rice vinegar = 10:1, add rice vinegar, stir-fry at 150°C for 15 minutes. Crush and pass through an 80-mesh sieve to obtain the processed nine-scented insect.

[0035] Preferably, in the method for preparing asafoetida, the wine used for the wine preparation is rice wine, and the weight ratio of asafoetida to rice wine is 8-10:1.

[0036] Further preferably, in the method for preparing asafoetida, the weight ratio of asafoetida to rice wine is 10:1.

[0037] Further preferably, the processing method of the asafoetida is as follows: take the original asafoetida, remove impurities, cut into small pieces, add yellow wine at a weight ratio of asafoetida to yellow wine = 10:1, and soak. After the yellow wine is completely absorbed, it is set aside.

[0038] Preferably, in the method for processing costus root, the wine used for the wine making is rice wine, and the weight ratio of the costus root slices to rice wine is 10-15:1.

[0039] Further preferably, in the method for preparing costus root, the weight ratio of the costus root slices to rice wine is 15:1.

[0040] More preferably, the processing method of costus root is as follows: after washing the costus root raw material, add 25°C water to cover the material, soak for 20 minutes, remove it into a basket to drain the water, transfer it into a jar, cover it and let it soak, take it out after soaking, slice it, dry it in the sun, and obtain costus root slices. According to the weight ratio of costus root slices to rice wine of 15:1, add rice wine for soaking. After the rice wine is completely absorbed, the processed costus root is obtained.

[0041] Preferably, in the processing method of cloves, the frying is performed at 120-150° C. for 15-20 min.

[0042] Further preferably, in the processing method of cloves, the frying is performed at 120° C. for 20 minutes.

[0043] Preferably, in the processing method of cloves, the crushing and screening is crushing through a 100-mesh sieve.

[0044] More preferably, the processing method of cloves is: put cloves into a frying container, fry at 120° C. for 20 minutes, crush and pass through a 100-mesh sieve to obtain processed cloves.

[0045] Specifically, the processing method of the terminalia chebula comprises: removing impurities, washing, drying, and crushing through a 10-mesh sieve to obtain the processed terminalia chebula for later use.

[0046] Specifically, the processing method of Cordyceps sinensis is as follows: take the original medicinal materials, remove impurities, brush off the soil, sieve off the ash, and obtain the processed Cordyceps sinensis for later use.

[0047] Specifically, the preparation method of the pharmaceutical composition comprises:

[0048] S1, mix rhubarb, turmeric, schisandra, asafoetida, costusroot, clove, terminalia chebula and cordyceps, add ethanol for reflux extraction, collect the extract to obtain extract 1, and collect the residue for later use;

[0049] S2, adding ethanol to the residue for reflux extraction, collecting the extract to obtain extract 2;

[0050] S3, combining the extract 1 and the extract 2, recovering the ethanol, drying, and crushing to obtain a pharmaceutical composition.

[0051] Preferably, the ethanol added in step S1 is 80%-90% ethanol.

[0052] Further preferably, the ethanol added in step S1 is 85% ethanol.

[0053] Preferably, the adding of ethanol in step S1 is performed at a liquid-to-solid ratio of 10 mL:1 g.

[0054] Preferably, the temperature of the reflux extraction in step S1 is 80° C., and the extraction time is 1-2 h.

[0055] Preferably, the ethanol added in step S2 is 85% ethanol which is 5 times the amount of the medicinal residue.

[0056] Preferably, the temperature of the reflux extraction in step S2 is 80° C., and the extraction time is 2 h.

[0057] Preferably, the drying in step S3 is freeze-drying.

[0058] Preferably, the pulverizing in step S3 is pulverizing into 100 mesh powder.

[0059] In another aspect, the present invention provides use of the above-mentioned pharmaceutical composition in the preparation of anti-tumor drugs.

[0060] Specifically, the tumor includes, but is not limited to, a digestive system tumor, a respiratory system tumor, a musculoskeletal system tumor, a nervous system tumor, an endocrine system tumor, a circulatory system tumor, a urinary system tumor or a reproductive system tumor.

[0061] Preferably, the tumor is hepatocellular carcinoma.

[0062] On the other hand, the present invention provides a medicine containing the above-mentioned pharmaceutical composition, and the medicine also includes a pharmaceutically acceptable excipient.

[0063] Specifically, the pharmaceutically acceptable excipients include, but are not limited to, solvents, diluents, disintegrants, precipitation inhibitors, surfactants, glidants, adhesives, lubricants, dispersants, suspending agents, isotonic agents, thickeners, emulsifiers, preservatives, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, colorants, flavoring agents, sweeteners, ion exchangers, release agents, coating agents, flavoring agents or antioxidants.

[0064] Specifically, the dosage forms of the medicine include decoctions, granules, pills, powders, ointments, pills, wines, syrups, lozenges, lotions, gels, teas, nails, sticks, suppositories, kojis, pastes, cakes, lotions, oils, threads, strips, ironing agents, roasting agents or smoke agents.

[0065] Preferably, the dosage form of the drug is granules.

[0066] The beneficial effects of the present invention are:

[0067] The pharmaceutical composition provided by the present invention can significantly inhibit the in vitro survival rate of HepG2 cells, can effectively improve the tumor volume and serum tumor markers AFP and TSGF levels of hepatocellular carcinoma mice, and provides a good development prospect for the preparation of anti-tumor drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Figure 1 is the cell viability.

[0069] Figure 2 Figure 2 is the tumor growth curve; Figure A is the tumor growth curve of mice in the model control group; Figure B is the tumor growth curve of mice in the 5-FU group and the drug composition group.

[0070] Figure 3 The serum tumor markers AFP and TSGF levels were measured by Elisa; A in the figure is the AFP level; B is the TSGF level. DETAILED DESCRIPTION

[0071] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0072] Example 1 Preparation of pharmaceutical composition

[0073] 1. Preparation of API

[0074] 1.1 Preparation of Rhubarb

[0075] Remove impurities from rhubarb, wash, slice, dry, and sieve out debris to obtain rhubarb slices. Add yellow rice wine in a weight ratio of 12:1 to rhubarb slices for soaking. After the yellow rice wine is completely absorbed, stir-fry at 180℃ for 15 minutes. Crush through an 80-mesh sieve to obtain the processed rhubarb for later use.

[0076] 1.2 Preparation of Turmeric

[0077] Remove impurities, wash, add 25℃ water to cover the herbs, soak for 1 hour, remove into a basket to drain the water, transfer to a jar, cover and let it soak, remove after soaking, slice, dry in the sun, and get turmeric slices. Add yellow wine at a weight ratio of turmeric slices: yellow wine = 3:1, stir-fry at 120℃ for 20 minutes, and get the processed turmeric, set aside.

[0078] 1.3 Preparation of Jiuxiangchong

[0079] According to the weight ratio of nine-scented worms to rice wine = 12:1, add rice wine to the nine-scented worms, mix well, and let it soak. After the rice wine is completely absorbed, stir-fry at 180℃ for 10 minutes. According to the weight ratio of nine-scented worms to rice vinegar = 10:1, add rice vinegar and stir-fry at 150℃ for 15 minutes. Crush through an 80-mesh sieve to obtain the processed nine-scented worms and set aside.

[0080] 1.4 Preparation of Asafoetida

[0081] Take the original medicinal material of Ferula, remove impurities, cut into small pieces, add yellow wine at a weight ratio of Ferula: yellow wine = 10:1, and soak it. After the yellow wine is completely absorbed, set aside.

[0082] 1.5 Preparation of costusroot

[0083] After washing the original material of costus root, add 25℃ water to cover the material, soak for 20 minutes, remove it into a basket to drain the water, transfer it into a jar, cover it and let it soak thoroughly, take it out, slice it, dry it in the sun, and get costus root slices. According to the weight ratio of costus root slices to rice wine of 15:1, add rice wine to soak it. After the rice wine is completely absorbed, you will get the processed costus root, which is ready for use.

[0084] 1.6 Preparation of Cloves

[0085] Put cloves into a frying container, fry at 120℃ for 20 minutes, crush through a 100-mesh sieve, and get the processed cloves for later use.

[0086] 1.7 Preparation of Terminalia chebula

[0087] Remove impurities, wash and dry. Grind through a 10-mesh sieve to obtain the processed Terminalia chebula for later use.

[0088] 1.8 Preparation of Cordyceps sinensis

[0089] Take the original medicinal materials, remove impurities, brush off the dirt, sieve out the ash, and get the processed Cordyceps sinensis for later use.

[0090] 2. Preparation of pharmaceutical composition

[0091] 180g of rhubarb, 180g of turmeric, 135g of scutellaria baicalensis, 90g of asafoetida, 90g of costusroot, 90g of clove, 117g of terminalia chebula and 18g of cordyceps sinensis were mixed evenly, and then 85% ethanol (liquid-to-solid ratio was 10mL:1g) was added, and the mixture was boiled and refluxed at 80°C for 2 hours to obtain extract 1. The residue was boiled and refluxed at 80°C for 2 hours with 5 times the amount of 85% ethanol to obtain extract 2. Extract 1 and extract 2 were combined, and ethanol was recovered to obtain a medicinal solution, which was freeze-dried in a freeze dryer and air flow crushed into 100 mesh powder to obtain a pharmaceutical composition.

[0092] Example 2 Preparation of pharmaceutical composition

[0093] 1. Preparation of API

[0094] 1.1 Preparation of Rhubarb

[0095] Remove impurities from rhubarb, wash, slice, dry, and sieve out debris to obtain rhubarb slices. Add yellow rice wine in a weight ratio of 10:1 to rhubarb slices for soaking. After the yellow rice wine is completely absorbed, stir-fry at 200℃ for 10 minutes. Crush through an 80-mesh sieve to obtain the processed rhubarb for later use.

[0096] 1.2 Preparation of Turmeric

[0097] Remove impurities, wash, add 25℃ water to cover the herbs, soak for 1 hour, remove into a basket to drain the water, transfer to a jar, cover and let it soak, remove after soaking, slice, dry in the sun, and get turmeric slices. Add yellow wine at a weight ratio of turmeric slices: yellow wine = 5:1, stir-fry at 150℃ for 15 minutes, and get the processed turmeric, set aside.

[0098] 1.3 Preparation of Jiuxiangchong

[0099] According to the weight ratio of nine-scented worms to rice wine = 10:1, add rice wine to the nine-scented worms, mix well, and let it soak. After the rice wine is completely absorbed, stir-fry at 200℃ for 8min. According to the weight ratio of nine-scented worms to rice vinegar = 5:1, add rice vinegar, stir-fry at 120℃ for 20min. Crush through an 80-mesh sieve to obtain the processed nine-scented worms and set aside.

[0100] 1.4 Preparation of Asafoetida

[0101] Take the original medicinal material of Ferula, remove impurities, cut into small pieces, add yellow wine at a weight ratio of Ferula: yellow wine = 8:1, and soak it. After the yellow wine is completely absorbed, set aside.

[0102] 1.5 Preparation of costusroot

[0103] After washing the original material of costus root, add 25℃ water to cover the material, soak for 20 minutes, remove it into a basket to drain the water, transfer it into a jar, cover it and let it soak thoroughly, take it out, slice it, dry it in the sun, and get costus root slices. According to the weight ratio of costus root slices to rice wine of 10:1, add rice wine to soak it. After the rice wine is completely absorbed, the processed costus root is obtained and set aside.

[0104] 1.6 Preparation of Cloves

[0105] Put cloves into a frying container, fry at 150℃ for 15 minutes, crush through a 100-mesh sieve, and get the processed cloves for later use.

[0106] 1.7 Preparation of Terminalia chebula

[0107] Remove impurities, wash and dry. Grind through a 10-mesh sieve to obtain the processed Terminalia chebula for later use.

[0108] 1.8 Preparation of Cordyceps sinensis

[0109] Take the original medicinal materials, remove impurities, brush off the dirt, sieve out the ash, and get the processed Cordyceps sinensis for later use.

[0110] 2. Preparation of pharmaceutical composition

[0111] 150g of rhubarb, 150g of turmeric, 112.5g of scutellaria baicalensis, 75g of asafoetida, 75g of costusroot, 75g of clove, 97.5g of terminalia chebula and 15g of cordyceps sinensis were mixed evenly, and then 85% ethanol (liquid-to-solid ratio was 10mL:1g) was added, and the mixture was boiled and refluxed at 80°C for 2 hours to obtain extract 1. The residue was boiled and refluxed at 80°C for 2 hours with 5 times the amount of 85% ethanol to obtain extract 2. Extract 1 and extract 2 were combined, and ethanol was recovered to obtain a medicinal solution, which was freeze-dried in a freeze dryer and air flow crushed into 100 mesh powder to obtain a pharmaceutical composition.

[0112] Example 3 Preparation of pharmaceutical composition

[0113] 1. The preparation of the raw material is the same as in Example 1.

[0114] 2. Preparation of pharmaceutical composition

[0115] 200g of rhubarb, 200g of turmeric, 150g of scutellaria baicalensis, 100g of asafoetida, 100g of costusroot, 100g of clove, 130g of terminalia chebula and 20g of cordyceps were mixed evenly, and then 85% ethanol (liquid-to-solid ratio was 10mL:1g) was added, and the mixture was boiled and refluxed at 80°C for 2 hours to obtain extract 1. The residue was boiled and refluxed at 80°C for 2 hours with 5 times the amount of 85% ethanol to obtain extract 2. Extract 1 and extract 2 were combined, and ethanol was recovered to obtain a medicinal solution, which was freeze-dried in a freeze dryer and air flow crushed into 100 mesh powder to obtain a pharmaceutical composition.

[0116] Comparative Example 1 Preparation of pharmaceutical composition

[0117] The difference between Comparative Example 1 and Example 1 is only that: 1.1 The processing of rhubarb is different.

[0118] 1.1 Preparation of Rhubarb

[0119] Remove impurities from rhubarb, wash, slice, dry, sieve to remove debris, and obtain rhubarb slices. Stir-fry at 180℃ for 15min. Crush through 80-mesh sieve to obtain processed rhubarb, and set aside.

[0120] Comparative Example 2 Preparation of pharmaceutical composition

[0121] The difference between Comparative Example 2 and Example 1 is only that: 1.2 The processing of turmeric is different.

[0122] 1.2 Preparation of Turmeric

[0123] Remove impurities, wash, add 25℃ water to cover the herbs, soak for 1 hour, remove into a basket to drain the water, transfer to a jar, cover and let it soak, take it out, slice it, dry it in the sun, and get turmeric slices. Stir-fry at 120℃ for 20 minutes to get the processed turmeric, set aside.

[0124] Comparative Example 3 Preparation of pharmaceutical composition

[0125] The difference between Comparative Example 3 and Example 1 is only that: 1.3 The processing of the nine-scented insect is different.

[0126] 1.3 Preparation of Jiuxiangchong

[0127] According to the weight ratio of Jiuxiangchong: Huangjiu = 12:1, add Huangjiu to Jiuxiangchong, mix well, and let it soak. After the Huangjiu is completely absorbed, stir-fry at 180℃ for 10 minutes. Crush through an 80-mesh sieve to obtain the processed Jiuxiangchong, and set aside.

[0128] Comparative Example 4 Preparation of pharmaceutical composition

[0129] The difference between Comparative Example 4 and Example 1 is that: 1.1 the processing of rhubarb, 1.2 the processing of turmeric, and 1.3 the processing of nine fragrant insects are different.

[0130] 1.1 Preparation of Rhubarb

[0131] Remove impurities from rhubarb, wash, slice, dry, sieve to remove debris, and obtain rhubarb slices. Stir-fry at 180℃ for 15min. Crush through 80-mesh sieve to obtain processed rhubarb, and set aside.

[0132] 1.2 Preparation of Turmeric

[0133] Remove impurities, wash, add 25℃ water to cover the herbs, soak for 1 hour, remove into a basket to drain the water, transfer to a jar, cover and let it soak, take it out, slice it, dry it in the sun, and get turmeric slices. Stir-fry at 120℃ for 20 minutes to get the processed turmeric, set aside.

[0134] 1.3 Preparation of Jiuxiangchong

[0135] According to the weight ratio of Jiuxiangchong: Huangjiu = 12:1, add Huangjiu to Jiuxiangchong, mix well, and let it soak. After the Huangjiu is completely absorbed, stir-fry at 180℃ for 10 minutes. Crush through an 80-mesh sieve to obtain the processed Jiuxiangchong, and set aside.

[0136] Comparative Example 5 Preparation of pharmaceutical composition

[0137] The only difference between Comparative Example 5 and Example 1 is that the processing of 1.4 Ferula, the processing of 1.5 Aucklandia lappa, and the processing of 1.6 Cloves are different.

[0138] 1.4 Preparation of Asafoetida

[0139] Take the original medicinal material of Ferula, remove impurities, cut into small pieces, add rice vinegar according to the weight ratio of Ferula: rice vinegar = 10:1, and soak it. After the rice vinegar is absorbed, set aside.

[0140] 1.5 Preparation of costusroot

[0141] After washing the original costus root materials, add 25℃ water to cover the materials, soak for 20 minutes, scoop them into a basket to drain the water, transfer them into a jar, cover it and let it soak thoroughly, take it out, slice it, dry it in the sun, and get costus root slices for later use.

[0142] 1.6 Preparation of Cloves

[0143] Put cloves into a frying container, fry at 120℃ for 20 minutes, crush through a 100-mesh sieve, and get the processed cloves for later use.

[0144] Comparative Example 6 Preparation of Pharmaceutical Composition

[0145] The only differences between Comparative Example 6 and Example 1 are: 1.1 The processing of rhubarb, 1.2 The processing of turmeric, 1.3 The processing of nine-scented insect, 1.4 The processing of asafoetida, 1.5 The processing of costus root, and 1.6 The processing of cloves are different.

[0146] 1.1 Preparation of Rhubarb

[0147] Remove impurities from rhubarb, wash, slice, dry, sieve to remove debris, and obtain rhubarb slices. Stir-fry at 180℃ for 15min. Crush through 80-mesh sieve to obtain processed rhubarb, and set aside.

[0148] 1.2 Preparation of Turmeric

[0149] Remove impurities, wash, add 25℃ water to cover the herbs, soak for 1 hour, remove into a basket to drain the water, transfer to a jar, cover and let it soak, take it out, slice it, dry it in the sun, and get turmeric slices. Stir-fry at 120℃ for 20 minutes to get the processed turmeric, set aside.

[0150] 1.3 Preparation of Jiuxiangchong

[0151] According to the weight ratio of Jiuxiangchong: Huangjiu = 12:1, add Huangjiu to Jiuxiangchong, mix well, and let it soak. After the Huangjiu is completely absorbed, stir-fry at 180℃ for 10 minutes. Crush through an 80-mesh sieve to obtain the processed Jiuxiangchong, and set aside.

[0152] 1.4 Preparation of Asafoetida

[0153] Take the original medicinal material of Ferula, remove impurities, cut into small pieces, add rice vinegar according to the weight ratio of Ferula: rice vinegar = 10:1, and soak it. After the rice vinegar is absorbed, set aside.

[0154] 1.5 Preparation of costusroot

[0155] After washing the original costus root materials, add 25℃ water to cover the materials, soak for 20 minutes, scoop them into a basket to drain the water, transfer them into a jar, cover it and let it soak thoroughly, take it out, slice it, dry it in the sun, and get costus root slices for later use.

[0156] 1.6 Preparation of Cloves

[0157] Put cloves into a frying container, fry at 120℃ for 20 minutes, crush through a 100-mesh sieve, and get the processed cloves for later use.

[0158] Experimental Example 1 Effect of the drug composition on the survival rate of HepG2 cells

[0159] 1. Cultivation of human liver cancer cell line HepG2

[0160] Human hepatoma cell line HepG2 was purchased from Wuhan Punosai, catalog number CL-0103. It was cultured in DMEM high-glucose medium containing 10% v / v fetal bovine serum at 37°C and 5% CO2. It was digested with 0.25% trypsin.

[0161] 2. Preparation of DMEM high-glucose medium containing different drug composition solutions

[0162] The pharmaceutical compositions prepared in Examples 1-3 and Comparative Examples 1-6 were respectively prepared into 20% w / v aqueous solutions, boiled for 1 hour, and added to DMEM high-glucose medium to make the concentration of the pharmaceutical composition in the medium 10% (w / v). DMEM high-glucose medium containing different pharmaceutical compositions was obtained.

[0163] 3. HepG2 cell survival rate determination

[0164] Take cells in the logarithmic growth phase and add cell suspension at 1×10 4 The cells were inoculated at a density of 100 μL in a 96-well plate, and 100 μL DMEM high-glucose medium was added to each well and placed in an incubator. After the cells adhered to the wall, the old medium was discarded, and 100 μL DMEM high-glucose medium containing different drug compositions was added respectively. The control group was added with 100 μL DMEM high-glucose medium containing 0.01% DMSO. Three replicate wells were set up for each group. After culturing at 37°C for 48 hours, the original medium was discarded. 10 μL DMEM high-glucose medium containing MTS labeling reagent was added to each well (culture medium: MTS labeling reagent = 5:1) and cultured at 37°C for 2 hours. The absorbance value at 490 nm was detected and recorded using an enzyme reader to calculate the cell viability. Cell viability (%) = experimental group OD / control group OD × 100%.

[0165] Experimental Example 2 Study on the effect of the drug composition on mouse hepatocellular carcinoma

[0166] 1. Model construction and grouping

[0167] The present invention uses 20 SPF-grade BALB / c nude mice, male, 4-5 weeks old, 12-14 g. Each mouse is housed in a single cage, free to drink water and eat, and the cages, bedding, drinking water and food are all sterilized.

[0168] HepG2 cells in the logarithmic growth phase were suspended in serum-free DMEM to prepare a hepatoma cell (HepG2) suspension, and the concentration was adjusted to 1×10 7 / mL, the cell suspension was extracted with a 1mL syringe and inoculated into each group, and 0.2mL was inoculated into the subcutaneous tissue of the right axilla (forelimb) of each nude mouse (except the blank negative control group) to establish a liver cancer model. BALB / c nude mice were randomly divided into a blank control group, a model control group, a 5-FU (5-fluorouracil) group, and a drug combination group, with 5 mice in each group. One week after the injection of HepG2 cell suspension, drug administration began (D0), once a day, for 15 consecutive days.

[0169] Blank control group: intragastric administration of an equal volume of normal saline;

[0170] Model control group: gavage with an equal volume of normal saline;

[0171] 5-FU group: intragastrically administered 25 mg / kg 5-FU;

[0172] Drug composition group: 10 g / kg of the drug composition prepared in Example 1 was administered intragastrically.

[0173] 2. Inspection indicators

[0174] During the administration period, the long diameter (a) and short diameter (b) of the tumor were measured with a vernier caliper every 5 days, and the tumor volume (V = 1 / 2 × a × b²) was calculated and recorded. Irregularly shaped tumors: a is measured by the longest diameter, and b is measured by the middle value of the short diameter perpendicular to the longest diameter. One hour after the last administration, blood was collected from the eye sockets, and the supernatant was obtained after centrifugation. The serum tumor markers AFP and TSGF levels were detected by ELISA.

[0175] The test results showed that the drug composition group was able to reduce tumor volume and the levels of tumor markers AFP and TSGF, and the effect was comparable to that of the positive control group 5-FU group.

[0176] The above detailed description is a specific description of one of the feasible embodiments of the present invention, and the embodiment is not intended to limit the scope of the present invention. It should be pointed out that any equivalent implementation or change that does not deviate from the present invention should be included in the scope of the technical solution of the present invention. Therefore, the protection scope of the patent of the present invention shall be based on the attached requirements.

Claims

1. A pharmaceutical composition, characterized in that The pharmaceutical composition is composed of rhubarb, turmeric, schizonepeta tenuifolia, asafoetida, costusroot, clove, terminalia chebula and cordyceps sinensis; the preparation method of the rhubarb, turmeric, schizonepeta tenuifolia, asafoetida, costusroot, clove, terminalia chebula and cordyceps sinensis is as follows: The rhubarb preparation method is as follows: rhubarb slices, wine making, frying, crushing and sieving; the wine used in the wine making is yellow rice wine, and the weight ratio of the rhubarb slices to the yellow rice wine is 10-12:1; The turmeric processing method is as follows: slicing turmeric, making wine, and frying; the wine used in the wine making is yellow wine, and the weight ratio of the turmeric slices to the yellow wine is 3-5:1; The preparation method of the nine-scented insect is as follows: after the nine-scented insect is mixed with rice wine, it is steamed, and after the rice wine is completely absorbed, it is fried, and rice vinegar is added, and the frying is continued, and the mixture is crushed and sieved; the weight ratio of the nine-scented insect to the rice wine is 10-12:1, and the weight ratio of the nine-scented insect to the rice vinegar is 5-10:1; The processing method of the asafoetida is as follows: the asafoetida is cut into pieces and processed with wine; the wine used in the processing is yellow wine, and the weight ratio of the asafoetida to the yellow wine is 8-10:1; The processing method of costus root is as follows: cutting costus root into slices and making wine; The wine used in the wine making process is yellow rice wine, and the weight ratio of the costusroot slices to the yellow rice wine is 10-15:1; The processing method of cloves is as follows: frying cloves, crushing and sieving; The pharmaceutical composition comprises, by weight, 150-200 parts of rhubarb, 150-200 parts of turmeric, 112-150 parts of nine-scented insect, 75-100 parts of asafoetida, 75-100 parts of costusroot, 75-100 parts of clove, 95-130 parts of terminalia chebula and 15-20 parts of cordyceps; The preparation method of the pharmaceutical composition comprises: S1, mix rhubarb, turmeric, schisandra, asafoetida, costusroot, clove, terminalia chebula and cordyceps, add ethanol for reflux extraction, collect the extract to obtain extract 1, and collect the residue for later use; S2, adding ethanol to the residue for reflux extraction, collecting the extract to obtain extract 2; S3, combining the extract 1 and the extract 2, recovering the ethanol, drying, and crushing to obtain a pharmaceutical composition.

2. The pharmaceutical composition according to claim 1, characterized in that In the processing method of rhubarb, the frying is performed at 180-200° C. for 10-15 minutes.

3. The pharmaceutical composition according to claim 1, characterized in that In the preparation method of rhubarb, the crushing and screening is crushing through an 80-mesh sieve.

4. The pharmaceutical composition according to claim 1, characterized in that In the turmeric processing method, the frying is performed at 120-150° C. for 15-20 minutes.

5. The pharmaceutical composition according to claim 1, characterized in that In the processing method of the nine-scented insect, the frying is frying at 180-200° C. for 8-10 minutes, and the continued frying is frying at 120-150° C. for 15-20 minutes.

6. The pharmaceutical composition according to claim 1, characterized in that In the preparation method of the nine-scented insect, the crushing and screening is crushing through an 80-mesh sieve.

7. The pharmaceutical composition according to claim 1, characterized in that In the processing method of cloves, the frying is performed at 120-150° C. for 15-20 minutes.

8. The pharmaceutical composition according to claim 1, characterized in that In the processing method of cloves, the crushing and screening is crushing through a 100-mesh sieve.

9. Use of the pharmaceutical composition according to any one of claims 1 to 8 in the preparation of an anti-hepatocellular carcinoma drug.

10. A drug, characterized in that The medicine is composed of the pharmaceutical composition according to any one of claims 1 to 8 and pharmaceutically acceptable excipients.

11. The drug according to claim 10, characterized in that The dosage form of the medicine includes decoction, granules, pills, powders, ointments, pills, wine, syrups, lozenges, lotions, gels or teas.

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