Traditional Chinese medicine compound tablet for treating osteosarcoma and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine compound tablet for treating osteosarcoma and a preparation method of the traditional Chinese medicine compound tablet, the tablet takes a Huanghome medicine circle osteosarcoma basic formula as a core, is prepared from 18 medicinal materials such as rhizoma pleionis, berba aristolochiae mollissimae, angelica sinensis and the like, and is optimized by a modern pharmaceutical technology. The preparation method comprises the following steps: performing enzymolysis and detoxification on radix aconiti and radix aconiti kusnezoffii, performing nanocrystallization on natural copper, performing freeze-drying-superfine grinding on insect medicines, extracting other medicinal materials, mixing, combining with a bone targeting carrier, and tabletting. The invention solves the problems of high toxicity, low bioavailability, poor targeting property and the like of the traditional prescription, has the advantages of obvious toxicity reduction, obvious synergism, stable active components, optimized dosage form, compliance of process and the like, and is suitable for treating osteosarcoma.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine compound preparations and anti-tumor drugs, in particular to a traditional Chinese medicine compound tablet for treating osteosarcoma and a preparation method thereof. Background Art

[0002] Osteosarcoma is a common malignant bone tumor. Traditional treatments are associated with significant side effects and high recurrence rates. Traditional Chinese medicine (TCM) offers unique advantages in osteosarcoma treatment, but clinical applications of traditional TCM formulas face numerous limitations: Toxicity: Radix Aconitum (Chuanwu) and Radix Aconitum (Kouwu) contain diester alkaloids (such as aconitine), which are highly toxic and difficult to control with traditional decoctions, leading to adverse reactions such as cardiotoxicity. Low bioavailability: The active peptides of insect-derived drugs (scorpions and centipedes) are easily destroyed, and mineral drugs (natural copper) are poorly absorbed by the body, limiting their efficacy. Poor targeting: Drugs are dispersed throughout the body, resulting in low concentrations at the site of bone tumors, impacting efficacy. Formulation defects: Traditional decoctions suffer from unstable dosages, inconvenience, and storage difficulties.

[0003] The Huang Family Medical Circle's basic osteosarcoma formula (documented in the Huang Family Medical Circle Essentials for Cancer Prevention and Treatment) has demonstrated some efficacy in clinical practice, but the aforementioned issues limit its widespread application. Therefore, there is an urgent need to optimize this traditional formula through modern pharmaceutical technology to achieve the goals of "reducing toxicity, increasing efficacy, and achieving targeted delivery." Summary of the Invention

[0004] The purpose of the present invention is to provide a traditional Chinese medicine compound tablet for treating osteosarcoma and a preparation method thereof, aiming to solve the problems of high toxicity, low bioavailability, poor targeting, unstable active ingredients and unreasonable dosage form existing in traditional Chinese medicine prescriptions for treating osteosarcoma.

[0005] According to the purpose of the present invention, the present invention provides a traditional Chinese medicine compound tablet for treating osteosarcoma. The tablet is composed of the following raw materials in parts by weight: 25-35 parts of Psoralea corylifolia, 25-35 parts of Rhizoma Cynoglossi, 25-35 parts of Rhizoma Anemarrhenae, 25-35 parts of Rhizoma Sarcosae, 25-35 parts of Rhizoma Astragali, 10-15 parts of Rhizoma Chuanwu, 10-15 parts of Rhizoma Aconitum, 10-15 parts of Rhizoma Aconitum, 10-15 parts of Rhizoma Curcumae, 8-10 parts of Sanguisorba Officinalis, 5-7 parts of Scorpio, 2-5 parts of Scolopendra, 8-12 parts of Radix Penicillae Sinensis, 8-12 parts of Rhizoma Psoraleae, 8-12 parts of Rhizoma Drynariae, 8-12 parts of Copper Root, 5-7 parts of Dipsacus asper, and 5-7 parts of Licorice.

[0006] Furthermore, the invention is composed of the following raw materials in parts by weight: 30 parts of Tripterygium wilfordii, 30 parts of Rhizoma Cynanchifoliae, 30 parts of Radix Angelicae Sinensis, 30 parts of Radix Sarcosinae, 30 parts of Radix Astragali, 12 parts of Radix Aconiti Kusnezoffii, 12 parts of Rhizoma Trigonosciae, 12 parts of Rhizoma Curcumae, 9 parts of Sanguisorba Officinalis, 6 parts of Scorpio, 3 parts of Scolopendra, 10 parts of Herba Polygoni Multiflori, 10 parts of Psoralea corylifolia, 10 parts of Rhizoma Drynariae, 10 parts of Copper Root, 6 parts of Dipsacus asper, and 6 parts of Licorice.

[0007] Further, the tablet has a 45-minute cumulative dissolution rate of ≥ 85%, an acute toxicity test rat LD50 ≥ 18.3 g / kg, a hERG potassium channel inhibition rate of ≤ 3%, an adsorption amount in bone tissue of ≥ 4.8 times that of a common tablet, a tumor site radioactivity uptake rate of ≥ 3.6 times that of a common tablet, and a similarity of ≥ 96% to the common peak of the original decoction using HPLC fingerprint detection.

[0008] According to another object of the present application, the present application provides a preparation method of the above-mentioned traditional Chinese medicine compound tablet for treating osteosarcoma, comprising the following steps: a) Enzymatic detoxification of Chuanwu and Caowu; b) Nanometer treatment of natural copper; c) Freeze-drying and ultrafine grinding of scorpion and centipede; d) Extraction of the remaining medicinal materials; e) Mixing all the extracts and excipients, and then combining with the bone targeting carrier to press tablets.

[0009] Further, in step a), the specific process of enzymatic detoxification of Chuanwu and Caowu is as follows: β-glucosidase is added in an acetic acid buffer or a citric acid buffer with a pH of 5.0-5.2, the enzyme dosage is 200-220 U / g of medicinal materials, the reaction is carried out at 45-48°C for 3.5-4 hours, and the buffer solution dosage is 20-25 times the weight of the medicinal materials; after enzymolysis, ultrafiltration membrane with a molecular weight cutoff of 3000 daltons is used for purification, and the aconitine residual amount is ≤ 0.01 ppm.

[0010] Further, in step b), natural copper reacts with citric acid at a molar ratio of 1:2-1:2.1 to generate copper citrate nanoclusters at 60-65°C, the particle size of the nanoclusters is 5-10 nm, and the copper residual amount is ≤ 2 ppm.

[0011] Further, in step c), scorpion and centipede are pre-frozen at -40 to -45°C for 4-5 hours before ultrafine grinding, the D90 of the ground particles is ≤ 10 μm, and the active peptide retention rate is ≥ 95%.

[0012] Further, in step d), the extraction of the remaining medicinal materials includes: Water extraction: decoct Radix Angelicae Sinensis, Radix Astragali, Rhizoma Sparganii, Rhizoma Curculiginis, Fructus Psoraleae, Drynariae Rhizoma, Ramulus et Caulis Lloydiae, and Radix Glycyrrhizae 3 times, add 8-9 times the amount of water for the first time, decoct for 2-2.5 hours, add 6-7 times the amount of water for the second and third times, decoct for 1.5-2 hours, and combine and concentrate the filtrate to 1:1 (g / mL); Alcohol extraction: use 70-75% ethanol to reflux extract Sanguis Draconis and Rhizoma Psoraiae 2 times, each for 1.5-2 hours, and recover ethanol to obtain extract; Extraction of volatile oil: collect volatile oil from Herba Polygoni Multiflori and Herba Cynoglossi by steam distillation, and include it in β-cyclodextrin. The mass ratio of volatile oil to β-cyclodextrin is 1:6-1:7.

[0013] Furthermore, in step e), the bone-targeting carrier is a hydroxyapatite-hyaluronic acid complex, and its preparation method includes: precipitating a hydroxyapatite precursor and a medicinal material extract in a microreactor, coating the surface with hyaluronic acid with a molecular weight of 8000-10000 Daltons, and mixing with cross-linked sodium carboxymethyl cellulose after freeze-drying, with a drug loading of 90.5±2.3%; using a fluidized bed granulation method with an inlet air temperature of 60-65°C and an outlet air temperature of 40-42°C. The tablet weight after tableting is 0.5 g / tablet and the hardness is 8-11 kN.

[0014] Beneficial effects of the present invention: The traditional Chinese medicine compound tablets for treating osteosarcoma of the present invention and the preparation method thereof have the following advantages: first, the toxicity is greatly reduced: the residual aconitine content of Chuanwu and Caowu after enzymatic hydrolysis is ≤0.01ppm, the LD50 in rats is above 18.3g / kg, which is 2.7 times that of traditional water decoctions, the hERG potassium channel inhibition rate is ≤3%, and the safety is improved; second, the synergy is significantly enhanced: the bone-targeted carrier enables the drug adsorption amount in bone tissue to be more than 4.8 times that of ordinary tablets, the radioactive uptake rate at the tumor site is increased by 3.6 times, and the therapeutic effect is improved by 2.3 times; third, the active ingredients are stable: the retention rate of insect drug active peptides is ≥95%, the natural copper nanoclusters have high bioavailability and the copper residue is ≤2ppm; fourth, the dosage form is optimized: the cumulative dissolution of the tablets in 45 minutes is ≥85%, the tablets have good stability, and are easy to take and store. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 is a flow chart of a method according to an embodiment of the present invention; DETAILED DESCRIPTION The following is a further description of specific embodiments of the present invention. It should be noted that the description of these embodiments is intended to facilitate understanding of the present invention and does not constitute a limitation of the present invention. In addition, the technical features involved in the various embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

[0016] Example 1 A traditional Chinese medicine compound tablet for treating osteosarcoma, based on the Huang Family Medical Circle osteosarcoma basic formula and optimized through modern pharmaceutical technology. The specific technical solution is as follows: Formula composition The medicine is composed of the following ingredients by weight: 25 parts of sedge, 25 parts of rabdosia, 25 parts of angelica, 25 parts of farfugium, 25 parts of milkvetch, 10 parts of monkshood, 10 parts of grass monkshood, 10 parts of rhizoma sparganii, 10 parts of zedoary turmeric, 8 parts of dragon's blood, 5 parts of scorpion, 2 parts of centipede, 8 parts of herba selaginellae, 8 parts of psoralea, 8 parts of drynaria, 8 parts of natural copper, 5 parts of dogwood, and 5 parts of licorice.

[0017] Example 2 A traditional Chinese medicine compound tablet for treating osteosarcoma, which is optimized by modern pharmaceutical technology based on the osteosarcoma basic formula of Huangjia Yiqun, has the following technical solutions. Composition of the formula The medicine is composed of the following ingredients by weight: 35 parts of sedge, 35 parts of rabdosia, 35 parts of angelica, 35 parts of farfugium, 35 parts of milkvetch, 15 parts of monkshood, 15 parts of grass monkshood, 15 parts of rhizoma sparganii, 15 parts of zedoary turmeric, 10 parts of dragon's blood, 7 parts of scorpion, 5 parts of centipede, 12 parts of herba selaginellae, 12 parts of psoralea, 12 parts of drynaria, 12 parts of natural copper, 7 parts of dogwood, and 7 parts of licorice.

[0018] Example 3 A traditional Chinese medicine compound tablet for treating osteosarcoma, which is optimized by modern pharmaceutical technology based on the osteosarcoma basic formula of Huangjia Yiqun, has the following technical solutions. Composition of the formula The medicine is composed of the following ingredients by weight: 30 parts of sedge, 30 parts of rabdosia, 30 parts of angelica, 30 parts of farfugium, 30 parts of milkvetch, 12 parts of monkshood, 12 parts of grass monkshood, 12 parts of rhizoma sparganii, 12 parts of zedoary turmeric, 9 parts of dragon's blood, 6 parts of scorpion, 3 parts of centipede, 10 parts of herba selaginellae, 10 parts of psoralea, 10 parts of drynaria, 10 parts of natural copper, 6 parts of dogwood, and 6 parts of licorice.

[0019] Key process optimization Toxic component conversion: β-glucosidase is used to hydrolyze the double-ester alkaloids in monkshood and grass monkshood into low-toxicity single-ester alkaloids, with the residual amount controlled to be less than or equal to 0.01 ppm; Mineral drug nanocrystallization: natural copper reacts with citric acid to form copper citrate nanoclusters (particle size 5-10 nm), which improves the bioavailability and reduces the heavy metal residue; Insect drug stabilization: scorpion and centipede are treated by freeze-drying and ultrafine grinding to retain more than 95% of the active peptides, with the particle size controlled to be less than or equal to 10 μm; Bone-targeted delivery: the hydroxyapatite-hyaluronic acid complex is used as a carrier to improve the accumulation of the drug in the bone tumor site, with the drug loading amount reaching 90.5±2.3%; Extraction process: water extraction, alcohol extraction, and volatile oil extraction are combined to maximize the retention of effective components; Tablet forming: after fluidized bed granulation, tabletting is performed to control the tablet weight, hardness and dissolution rate, and ensure the stability of the dosage form.

[0020] Example 4 A traditional Chinese medicine compound tablet for treating osteosarcoma is composed of the following raw materials by weight: Yunzigou 30 parts, Xungufeng 30 parts, Danggui 30 parts, Zhongjie Feng 30 parts, Huangqi 30 parts, Chuanwu 12 parts, Cao Wu 12 parts, Sanleng 12 parts, E Zhi 12 parts, Xuejie 9 parts, Quanxie 6 parts, Wugong 3 parts, Tougucao 10 parts, Buguzhi 10 parts, Gushu Bu 10 parts, Zhenzhuang 10 parts, Xuduan 6 parts, Gancao 6 parts.

[0021] As shown in Figure 1 the preparation method of the above-mentioned traditional Chinese medicine compound tablet for treating osteosarcoma, comprising the following steps: a) enzymatic detoxification of Chuanwu and Cao Wu; b) nanocrystallization treatment of Zhenzhuang; c) freeze-drying and ultrafine grinding of Quanxie and Wugong; d) extraction of the remaining medicinal materials; e) mixing all the extracts and excipients, and tabletting after combining with bone targeting carriers.

[0022] Specifically, in step a), the specific process of enzymatic detoxification of Chuanwu and Cao Wu is as follows: β-glucosidase is added in a buffer solution with pH 5.0-5.2, the enzyme dosage is 200-220 U / g of medicinal materials, and the reaction is carried out at 45-48℃ for 3.5-4 hours.

[0023] Among them, the buffer solution is acetic acid buffer or citric acid buffer, and the dosage is 20-25 times the weight of the medicinal materials.

[0024] In step a), after enzymatic hydrolysis, ultrafiltration membrane with a molecular weight cutoff of 3000 daltons is used for purification, and the aconitine residual amount is ≤0.01 ppm.

[0025] Specifically, in step b), Zhenzhuang reacts with citric acid at a molar ratio of 1:2-1:2.1 to generate copper citrate nanoclusters at 60-65℃, and the particle size of the nanoclusters is 5-10 nm.

[0026] Specifically, in step c), Quanxie and Wugong are pre-frozen at-40 to-45℃ for 4-5 hours before ultrafine grinding, and the D90 of the ground particles is ≤10 μm, and the active peptide retention rate is ≥95%.

[0027] Specifically, in step d), the extraction of the remaining medicinal materials includes: Water extraction: decocted 3 times with water for Angelica sinensis, Astragalus membranaceus, Trigonosciadium japonicum, Curcuma zedoaria, Psoralea corylifolia, Drynaria fortunei, Dipsacus root, and Licorice root. The first time, add 8-9 times the amount of water and simmer for 2-2.5 hours. The second and third times, add 6-7 times the amount of water and simmer for 1.5-2 hours. The combined filtrates were concentrated to a 1:1 ratio (g / mL). Alcohol extraction: Use 70-75% ethanol to reflux extract twice, each time for 1.5-2 hours, and recover the ethanol to obtain the extract; Extraction of volatile oil: collect volatile oil from Herba Polygoni Multiflori and Herba Cynoglossi by steam distillation, and include it in β-cyclodextrin. The mass ratio of volatile oil to β-cyclodextrin is 1:6-1:7.

[0028] Specifically, in step e), the bone-targeting carrier is a hydroxyapatite-hyaluronic acid complex, and its preparation method includes: precipitating a hydroxyapatite precursor and a medicinal material extract in a microreactor, coating the surface with hyaluronic acid with a molecular weight of 8,000-10,000 Daltons, and mixing with cross-linked sodium carboxymethyl cellulose after freeze-drying.

[0029] The drug loading of the bone-targeted carrier was 90.5±2.3%.

[0030] In step e), fluidized bed granulation is adopted, with an air inlet temperature of 60-65°C and an air outlet temperature of 40-42°C.

[0031] Specifically, the tablets of this embodiment have a tablet weight of 0.5 g / tablet, a hardness of 8-11 kN, and a cumulative dissolution rate of ≥85% within 45 minutes.

[0032] The Chinese medicine compound tablets of this embodiment, in an acute toxicity test, showed a rat LD50 of ≥18.3 g / kg, an hERG potassium channel inhibition rate of ≤3%, an adsorption rate in bone tissue of 4.8 times that of ordinary tablets, and a radioactive uptake rate in tumor sites of 3.6 times that of ordinary tablets.

[0033] The residual copper content of the compound Chinese medicine tablets of this embodiment after conversion of natural copper is ≤2ppm. The compound Chinese medicine tablets of this embodiment, when tested by HPLC fingerprint, have a common peak similarity of ≥96% with the water decoction of the original formula.

[0034] Example 5 like Figure 1 As shown, a Chinese medicine compound tablet for treating osteosarcoma, the preparation of the Chinese medicine compound tablet comprises the following steps: Medicinal material pretreatment Detoxification of Aconiti Carmichaelii and Radix Aconiti Kusnezoffii: Take 12g of Aconiti Carmichaelii crude powder and 12g of Radix Aconiti Kusnezoffii crude powder, add 20 times the amount of pH 5.0 acetate buffer, add 2400U of β-glucosidase (200U / g medicinal material), stir at 45℃ for 4 hours, inactivate the enzyme at 80℃, and concentrate through a 3000Da ultrafiltration membrane. The residual aconitine is detected to be 0.008ppm. Native copper treatment: 10 g of native copper powder was reacted with 4.2 g of citric acid (molar ratio 1:2) at 60°C for 2 h to generate a copper citrate nanocluster solution (particle size 7.5 nm). Insect drug treatment: 6g of whole scorpion and 3 centipedes were pre-frozen at -40℃ for 4 hours and then ultrafinely crushed. The particle size test showed D50 = 3.2μm, D90 = 8.6μm, and the active peptide retention rate was 96.2%.

[0035] Extraction process Water extraction group: 8 herbs including Angelica sinensis, Astragalus membranaceus, Trillium gracile, Curcuma zedoaria, Psoralea corylifolia, Drynaria fortunei, Dipsacus root, and Licorice root were decocted three times with water (8 times the amount of water for the first decocting time, 2 hours; 6 times the amount of water for the second and third decocting times, 1.5 hours each). The filtrates were combined and concentrated to a 1:1 (g / mL) extract. Alcohol extraction group: Xuejie and Xungufeng were extracted twice with 70% ethanol under reflux (1.5 hours each time), and the ethanol was recovered to obtain the extract; Volatile oil group: Herba Polygoni Multiflori and Herba Sarcandrae were collected by steam distillation, included with β-cyclodextrin (volatile oil:β-cyclodextrin = 1:6), and dried to obtain inclusion complex.

[0036] Tablet forming Mixing: Evenly mix the enzymatically hydrolyzed Radix Aconiti Kusnezoffii extract, the Radix Aconiti Kusnezoffii extract, the natural copper nanoclusters, the insect powder, the water extract, the alcohol extract and the volatile oil inclusion compound; Carrier addition: Add hydroxyapatite-hyaluronic acid carrier (drug loading 90.5%) and cross-linked carboxymethyl cellulose sodium (disintegrant) and mix; Granulation and tableting: fluidized bed granulation (inlet air temperature 60℃, outlet air temperature 40℃), granule tableting, control tablet weight 0.5g / tablet, hardness 8-10kN.

[0037] Example 6 like Figure 1 As shown, a Chinese medicine compound tablet for treating osteosarcoma, the preparation of the Chinese medicine compound tablet comprises the following steps: Medicinal material pretreatment Detoxification of Aconitum carmichaelii and Aconitum kusnezoffii: Take 12g of Aconitum carmichaelii crude powder and 12g of Aconitum kusnezoffii crude powder, add 25 times the amount of pH 5.2 citric acid buffer, add 2600U β-glucosidase, stir at 48℃ for 3.5 hours, inactivate the enzyme at 85℃, and concentrate through a 3000Da ultrafiltration membrane. The residual aconitine is detected to be 0.006ppm. Native copper treatment: 10 g of native copper powder was reacted with 4.5 g of citric acid (molar ratio 1:2.1) at 65 °C for 1.5 h to generate a copper citrate nanocluster solution (particle size 6.2 nm). Insect drug treatment: take 6g scorpion, 3 centipedes, -45 ℃ pre-freezing 5 hours after ultrafine grinding, particle size detection D50=2.8μm, D90=7.9μm, active peptide retention rate 97.5%.

[0038] Extraction process Water extraction group: 8 kinds of medicinal materials such as angelica, radix astragali, etc. are added with water and decocted for 3 times (9 times the amount of water for the first time, decocting for 2.5 hours; 7 times the amount of water for the second and third times, decocting for 2 hours), and the filtrate is combined and concentrated to 1:1 (g / mL) extract; Alcohol extraction group: dragon's blood, xun guifeng, add 75% ethanol reflux extraction 2 times (2 hours each time), recover ethanol to get extract; Volatile oil group: tougucao, zhongjie wind, water vapor distillation to collect volatile oil, and β-cyclodextrin (volatile oil: β-cyclodextrin = 1:7) is packaged, and the package is dried.

[0039] Tablet forming Mixing: as in example 3; Carrier addition: add hydroxyapatite-hyaluronic acid carrier (drug loading 91.2%) and crosslinked carboxymethyl cellulose sodium, and mix; Granulation and tabletting: fluidized bed granulation (inlet air temperature 65℃, outlet air temperature 42℃), granule tabletting, control tablet weight 0.5g / tablet, hardness 9-11kN.

[0040] Performance testing Dissolution: 90.3% cumulative dissolution in 45 minutes; Acute toxicity: LD50=19.1g / kg in rats; Targeting: bone tissue adsorption is 5.1 times that of ordinary tablets.

[0041] Compared with the prior art, the present application has the following beneficial effects: Significant attenuation: after enzymatic hydrolysis of chuanwu and caowu, the aconitine residual amount is ≤0.01ppm, the LD50 of rats reaches 18.3g / kg (2.7 times that of traditional water decoction), and the hERG potassium channel inhibition rate is ≤3% (the traditional prescription is 22%), and the safety is greatly improved; Obvious synergistic effect: the bone targeting carrier makes the drug adsorption in bone tissue 4.8 times that of ordinary tablets, the tumor site radioactivity uptake rate increases by 3.6 times, and the curative effect increases by 2.3 times; Stable active ingredients: the active peptide retention rate of insect drugs is ≥95%, the bioavailability of natural copper nanoclusters is significantly improved, and heavy metal accumulation (copper residue ≤2ppm) is avoided; Optimized dosage form: tablet 45 minutes cumulative dissolution ≥85%, good stability (degradation rate of active ingredients <5% in 6 months of accelerated test), convenient to take and store; Process compliance: in line with the processing standards of Fuzi in Chinese Pharmacopoeia, FDA Q3D elemental impurity guidelines and international requirements for stability, with industrialization potential.

[0042] While the embodiments of the present patent have been shown and described, it is to be understood that the embodiments can be varied, modified, substituted and changed by those skilled in the art without departing from the principles and spirit of the present patent, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicinal compound tablet for treating osteosarcoma, characterized in that: The invention is composed of the following raw materials in parts by weight: 25-35 parts of Psoralea corylifolia, 25-35 parts of Rhizoma Cynanchifoliae, 25-35 parts of Radix Angelicae Sinensis, 25-35 parts of Rhizoma Sarcosae, 25-35 parts of Radix Astragali, 10-15 parts of Radix Aconiti Kusnezoffii, 10-15 parts of Rhizoma Trigonidis, 10-15 parts of Rhizoma Curcumae, 8-10 parts of Sanguisorba Officinalis, 5-7 parts of Scorpio, 2-5 parts of Scolopendra, 8-12 parts of Herba Polygoni Multiflori, 8-12 parts of Psoralea corylifolia, 8-12 parts of Rhizoma Drynariae, 8-12 parts of Copper Root, 5-7 parts of Dipsacus asper, and 5-7 parts of Radix Glycyrrhizae.

2. A Chinese medicine compound tablet for treating osteosarcoma, characterized in that: The invention is composed of the following raw materials in parts by weight: 30 parts of Psoralea corylifolia, 30 parts of Rhizoma Cynanchifoliae, 30 parts of Radix Angelicae Sinensis, 30 parts of Radix Sarcandrae, 30 parts of Radix Astragali, 12 parts of Radix Aconiti Kusnezoffii, 12 parts of Rhizoma Trigonidis, 12 parts of Rhizoma Curcumae, 9 parts of Sanguisorba Officinalis, 6 parts of Scorpio, 3 parts of Scolopendra, 10 parts of Herba Polygoni Multiflori, 10 parts of Psoralea corylifolia, 10 parts of Rhizoma Drynariae, 10 parts of Copper Root, 6 parts of Dipsacus asper, and 6 parts of Radix Glycyrrhizae.

3. The Chinese medicinal compound tablet for treating osteosarcoma according to claim 1, characterized in that: The tablet has a cumulative dissolution rate of ≥85% within 45 minutes, an LD50 of ≥18.3 g / kg in rats in an acute toxicity test, an hERG potassium channel inhibition rate of ≤3%, an adsorption amount in bone tissue of more than 4.8 times that of ordinary tablets, a radioactive uptake rate in tumor sites of more than 3.6 times that of ordinary tablets, and a common peak similarity of ≥96% with the original formula water decoction detected by HPLC fingerprint.

4. The method for preparing the Chinese medicinal compound tablet for treating osteosarcoma according to claim 1, wherein: The following steps are involved: a) Enzymatic detoxification of Aconitum carmichaelii and Aconitum kusnezoffii; b) Natural copper nano-processing; c) Freeze-dried and ultrafinely crushed scorpions and centipedes; d) Extraction of other medicinal materials; e) Mix all extracts and excipients, combine with bone targeting carrier and then compress into tablets.

5. The method for preparing the Chinese medicinal compound tablet for treating osteosarcoma according to claim 4, characterized in that: In step a), the specific process of enzymatic detoxification of Aconitum carmichaelii and Aconitum kusnezoffii is as follows: adding β-glucosidase to an acetate buffer or citric acid buffer at pH 5.0-5.2, the enzyme dosage is 200-220 U / g of medicinal material, reacting at 45-48° C. for 3.5-4 hours, and the amount of buffer used is 20-25 times the weight of the medicinal material; after enzymatic hydrolysis, purification is performed using an ultrafiltration membrane with a molecular weight cutoff of 3000 Daltons, and the residual aconitine content is ≤0.01 ppm.

6. The method for preparing the Chinese medicinal compound tablet for treating osteosarcoma according to claim 4, characterized in that: In step b), native copper and citric acid react at a molar ratio of 1:2-1:2.1 at 60-65° C. to generate copper citrate nanoclusters. The nanoclusters have a particle size of 5-10 nm and a copper residue of ≤2 ppm.

7. The method for preparing the Chinese medicinal compound tablet for treating osteosarcoma according to claim 4, characterized in that: In step c), the scorpion and centipede are pre-frozen at -40 to -45°C for 4-5 hours and then ultrafinely ground. The D90 of the ground particles is ≤10 μm, and the active peptide retention rate is ≥95%.

8. The method for preparing the Chinese medicinal compound tablet for treating osteosarcoma according to claim 4, characterized in that: In step d), the extraction of the remaining medicinal materials includes: Water extraction: decocted 3 times with water for Angelica sinensis, Astragalus membranaceus, Trigonosciadium japonicum, Curcuma zedoaria, Psoralea corylifolia, Drynaria fortunei, Dipsacus root, and Licorice root. The first time, add 8-9 times the amount of water and simmer for 2-2.5 hours. The second and third times, add 6-7 times the amount of water and simmer for 1.5-2 hours. The combined filtrates were concentrated to a 1:1 ratio (g / mL). Alcohol extraction: Use 70-75% ethanol to reflux extract twice, each time for 1.5-2 hours, and recover the ethanol to obtain the extract; Extraction of volatile oil: collect volatile oil from Herba Polygoni Multiflori and Herba Cynoglossi by steam distillation, and include it in β-cyclodextrin. The mass ratio of volatile oil to β-cyclodextrin is 1:6-1:

7.

9. The method for preparing the Chinese medicinal compound tablet for treating osteosarcoma according to claim 4, characterized in that: In step e), the bone-targeting carrier is a hydroxyapatite-hyaluronic acid complex, and its preparation method includes: precipitating a hydroxyapatite precursor and a medicinal extract in a microreactor, coating the surface with hyaluronic acid with a molecular weight of 8,000-10,000 Daltons, and mixing with cross-linked sodium carboxymethyl cellulose after freeze-drying to achieve a drug loading of 90.5±2.3%; using a fluidized bed granulation method with an inlet air temperature of 60-65°C and an outlet air temperature of 40-42°C. The tablet weight after tableting is 0.5 g / tablet and the hardness is 8-11 kN.

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