Anti-breast cancer traditional Chinese medicine compound preparation as well as preparation method and application thereof

Abstract

The invention discloses an anti-breast cancer traditional Chinese medicine compound preparation as well as a preparation method and application thereof. The anti-breast cancer traditional Chinese medicine compound preparation is prepared from the following raw material medicines in parts by weight: 25-35 parts of ganoderma lucidum spore powder, 10-20 parts of edible tulip, 10-20 parts of sculellaria barbata, 20-30 parts of oldenlandia diffusa, 8-12 parts of detoxified nidus vespae, 20-30 parts of selfheal, 10-20 parts of akebia fruit and 15-25 parts of uniflower swisscentaury root. Ganoderma lucidum spore powder is used as a monarch drug instead of a tonic drug, so that the risk of excessive activation of immunity is avoided; the retention rate of triterpenes is greater than or equal to 95% and the yield of polysaccharides is greater than or equal to 15% through a segmented extraction Establishing a nidus vespae detoxification process and a nidus vespae oil limit standard; by removing tumor-promoting risk medicinal materials, introducing active synergistic components and innovating a toxicity control process, the anti-tumor activity and medication safety are remarkably improved, and the composition is suitable for adjuvant therapy of breast cancer.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a compound traditional Chinese medicine preparation for treating breast cancer, its preparation method, and its application. Background Technology

[0002] Breast cancer is the most common malignant tumor among women worldwide. Its pathogenesis is complex, involving multiple factors such as hormonal imbalance, immune escape, and impaired apoptosis. In recent years, Traditional Chinese Medicine (TCM) has demonstrated unique advantages in the comprehensive treatment of breast cancer, particularly in regulating overall bodily functions, reducing the toxic side effects of radiotherapy and chemotherapy, delaying drug resistance, and inhibiting recurrence and metastasis. Based on the TCM theory of "strengthening the body's resistance and eliminating pathogenic factors, treating both the root cause and the symptoms," various TCM compound preparations have been widely researched and applied. Among them, the basic combination strategy of common anti-breast cancer compound preparations is to use tonifying herbs (such as Astragalus membranaceus and Codonopsis pilosula) to support the body's resistance, combined with heat-clearing, detoxifying, phlegm-resolving, and nodule-dispersing herbs (such as Scutellaria barbata, Cremastra appendiculata, Ganoderma lucidum spore powder, and Vespa nidus) to eliminate cancer toxins.

[0003] However, existing traditional Chinese medicine compound preparations for breast cancer still have significant technical defects in formulation and preparation processes, which seriously restrict their clinical efficacy and safety assurance. These defects are mainly reflected in the following three aspects: Formula compatibility defects: Tonifying herbs may activate immune cells in the tumor microenvironment, weakening the anti-tumor effect.

[0004] Traditional compound prescriptions often use large amounts of qi-tonifying and blood-nourishing herbs to "strengthen the body's resistance." However, modern research shows that some tonifying components may non-specifically activate immune cells in the tumor microenvironment (such as regulatory T cells and tumor-associated macrophages), thereby promoting the formation of an immunosuppressive microenvironment or stimulating tumor cell proliferation signaling pathways. This weakens the direct anti-tumor effects of heat-clearing, detoxifying, phlegm-resolving, and nodule-dispersing drugs to some extent, leading to mutual antagonism between the "strengthening the body's resistance" and "eliminating pathogenic factors" effects, thus limiting the overall efficacy.

[0005] Outdated extraction processes for key active ingredients lead to the loss of effective components or the residue of toxic components.

[0006] High Loss Rate of Lipid-Soluble Triterpenes in Ganoderma Lucidum Spore Powder: Triterpenoids (especially ganoderic acids) in Ganoderma Lucidum spore powder are the core substances for its antitumor activity, but they are significantly lipid-soluble. The currently widely used traditional water decoction extraction method has extremely low dissolution efficiency for these components, resulting in a loss rate of more than 40% of lipid-soluble triterpenes, which seriously reduces the biological activity of the preparation.

[0007] Nephrotoxicity of bee honeycomb volatile oil: While bee honeycomb, a commonly used anti-tumor traditional Chinese medicine, contains volatile oil components with certain pharmacological activities, some components (such as beeswax aldehydes and alkanes) have been proven to have potential nephrotoxicity. Current preparation methods often fail to specifically remove or transform the toxic components of bee honeycomb, resulting in residual nephrotoxic substances in the final formulation, posing a safety risk for long-term use.

[0008] The synergistic mechanism of the drug pair is unclear, the activity ratio is not optimized, and the efficacy is limited.

[0009] Cremastra appendiculata and Scutellaria barbata are commonly used drug pairs in anti-breast cancer compound formulas, both of which can induce tumor cell apoptosis. However, existing research mostly focuses on single-drug or simple combinations, lacking systematic studies on the specific molecular mechanisms and optimal active ingredient ratios of the synergistic apoptosis-inducing effects of Cremastra appendiculata (containing colchicine alkaloids) and Scutellaria barbata (containing flavonoids and coumarins). Clinical applications often employ empirical ratios, failing to maximize efficacy and resulting in insufficient apoptosis induction efficiency, thus limiting overall anti-tumor efficacy.

[0010] In summary, existing traditional Chinese medicine (TCM) compound preparations for breast cancer treatment have significant shortcomings in terms of scientific formulation, extraction efficiency of key components, toxicity control, and synergistic optimization of efficacy. Therefore, there is an urgent need to develop a novel TCM compound preparation for breast cancer treatment and its preparation method. Summary of the Invention

[0011] The purpose of this invention is to provide a traditional Chinese medicine compound preparation for breast cancer, its preparation method and its application, by removing tumor-promoting medicinal materials, introducing active synergistic components and innovating toxicity control processes to solve the above-mentioned technical problems.

[0012] The above-mentioned technical objective of the present invention is achieved through the following technical solution: A traditional Chinese medicine compound preparation for treating breast cancer is made from the following raw materials in parts by weight: 25-35 parts of Ganoderma lucidum spore powder, 10-20 parts of Cremastra appendiculata, 10-20 parts of Scutellaria barbata, 20-30 parts of Hedyotis diffusa, 8-12 parts of detoxified propolis, 20-30 parts of Prunella vulgaris, 10-20 parts of Citrus aurantium, and 15-25 parts of Echinops latifolius.

[0013] Further preferred formulations are made from the following raw materials in parts by weight: 20 parts Ganoderma lucidum spore powder, 15 parts Cremastra appendiculata, 15 parts Scutellaria barbata, 25 parts Hedyotis diffusa, 10 parts detoxified propolis, 25 parts Prunella vulgaris, 15 parts Citrus aurantium, and 20 parts Echinops latifolius.

[0014] This invention also provides a method for preparing a traditional Chinese medicine compound preparation for breast cancer, comprising the following steps: S1. Ganoderma lucidum spore powder, Pseudobulbus Cremastrae and Scutellaria barbata were classified as fat-soluble components extraction group. Supercritical CO2 extraction was used. Triterpenoid components were collected in separation vessel I at a pressure of 10 MPa and a temperature of 60℃, and alkaloid components were collected in separation vessel II at a pressure of 5 MPa and a temperature of 35℃. The products from the two separation vessels were combined and vacuum dried to obtain a brownish-yellow fat-soluble extract. S2. The white flower snake tongue grass, Yuzhizi and Echinopsis lanceolata were classified into the water-soluble component extraction group. They were extracted with hot water at 90℃ for 2 hours with a material-liquid ratio of 1:12. The extract was separated and enriched with polysaccharides through a ceramic membrane. The retentate was concentrated under reduced pressure to a relative density of 1.25 and spray-dried to obtain white polysaccharide powder. S3. Detoxification treatment of exposed honeycomb: Take dried exposed honeycomb medicinal material, crush it into 40 mesh using a pulverizer, and then put it into a supercritical CO2 extraction device. Under the conditions of constant pressure 35 MPa and constant temperature 45℃, dynamic circulation extraction is carried out at a CO2 flow rate of 25 liters per hour for 120 minutes to fully dissolve the nephrotoxic honeycomb oil components in the medicinal material and obtain detoxified exposed honeycomb. S4. Detoxified honeycomb and Prunella vulgaris were classified into the heat-sensitive component extraction group. They were extracted with 50% ethanol at 40℃ using dynamic countercurrent extraction to protect the flavonoid components. The ethanol was recovered under reduced pressure from the effluent, and the concentrate was freeze-dried to obtain a yellow-brown extract. S5. Combine the three extracts, add β-cyclodextrin and trehalose as protectants, spray dry to make dry powder, compress into tablets or fill capsules.

[0015] More preferably, in S1, the supercritical CO2 extraction pressure is 35 MPa, the temperature is 45 °C, and the entrainer is a 7:3 ratio of ethanol to water.

[0016] More preferably, in step S2, the filtration accuracy of the ceramic membrane is 10 kDa.

[0017] In a further preferred embodiment, in step S3, the detoxified honeycomb needs to be tested by gas chromatography to confirm that the residual honeycomb oil content is less than 100 ppm.

[0018] More preferably, in step S5, the mass ratio of β-cyclodextrin to trehalose is 1:1.

[0019] The application of the compound preparation obtained by this invention in the preparation of drugs that enhance the anti-breast cancer activity of 5-fluorouracil.

[0020] In summary, the present invention has the following beneficial effects: The present invention uses Ganoderma lucidum spore powder to replace the tonifying medicine as the monarch drug, avoiding the risk of over-activation of the immune system; the segmented extraction process enables the retention rate of triterpenes to be ≥95% and the polysaccharide yield to be ≥15%; a detoxification process for Nidus Vespae and a limit standard for Nidus Vespae oil are established; by removing the tumor-promoting risk medicinal materials, introducing active synergistic components, and innovating the toxicity control process, the anti-tumor activity and drug safety are significantly improved, and it is applicable to the adjuvant treatment of breast cancer. Brief Description of the Drawings

[0021] Figure 1 It is the synthesis method of the compound preparation in the present invention. Detailed Embodiments

[0022] The present invention will be further described in detail below with reference to the accompanying drawings.

[0023] Example: An anti-breast cancer traditional Chinese medicine compound preparation is made from the following raw materials in parts by weight: 1. Strengthening the healthy qi and consolidating the root: 25 parts of Ganoderma lucidum spore powder, the core monarch drug, enhancing the immune regulation function.

[0024] 2. Detoxifying and dissipating nodules: 10 parts of Cremastra appendiculata, mainly attacking phlegm and stasis binding, activating the apoptosis pathway; 10 parts of Scutellaria barbata, clearing heat and detoxifying, synergistically enhancing the anti-tumor activity; 20 parts of Hedyotis diffusa, clearing heat and promoting diuresis, enhancing the expression of CASP3 / 9.

[0025] 3. Resolving phlegm and softening hardness: 8 parts of detoxified Nidus Vespae, detoxified by CO2 supercritical extraction, dissipating carbuncles and nodules; 20 parts of Prunella vulgaris, clearing the liver and dissipating nodules, inhibiting the release of inflammatory factors.

[0026] 4. Soothing the liver and dredging collaterals: 10 parts of Schisandra rubriflora, replacing Akebia trifoliata, enhancing the effect of soothing the liver and regulating qi.

[0027] 5. Enhancing efficacy and guiding the meridian: 15 parts of Rhaponticum uniflorum, promoting menstruation and lactation, strengthening the regulation of the tumor microenvironment.

[0028] A preparation method of an anti-breast cancer traditional Chinese medicine compound preparation, as Figure 1 shown, includes the following steps: S1. Classify Ganoderma lucidum spore powder, Cremastra appendiculata and Scutellaria barbata into the lipid-soluble component extraction group, and use supercritical CO2 extraction. The pressure of supercritical CO2 extraction is 35 MPa, the temperature is 45 °C, and the entrainer is ethanol: water at a ratio of 7:3. The first separation kettle collects triterpene components at a pressure of 10 MPa and a temperature of 60 °C, and the second separation kettle collects alkaloid components at a pressure of 5 MPa and a temperature of 35 °C. The products of the two separation kettles are combined and vacuum dried to obtain 42.3 g of brown-yellow lipid-soluble extract (triterpene content 21.5%).

[0029] S2. The white flower snake tongue grass, Yuzhizi and Echinopsis lanceolata were classified into the water-soluble component extraction group. They were extracted with hot water at 90℃ for 2 hours with a material-to-liquid ratio of 1:12. The extract was filtered through a ceramic membrane with a filtration precision of 10kDa to separate and enrich polysaccharides. The retentate was concentrated under reduced pressure to a relative density of 1.25 and spray-dried to obtain a white polysaccharide powder.

[0030] S3. Detoxification treatment of exposed honeycomb: Take dried exposed honeycomb medicinal material, crush it into 40 mesh using a pulverizer, and then put it into a supercritical CO2 extraction device. Under constant pressure of 35 MPa and constant temperature of 45℃, perform dynamic circulation extraction at a CO2 flow rate of 25 liters per hour for 120 minutes to fully dissolve the nephrotoxic honeycomb oil component in the medicinal material and obtain detoxified exposed honeycomb. The detoxified exposed honeycomb needs to be detected by gas chromatography to confirm that the honeycomb oil residue is less than 100 ppm.

[0031] S4. Detoxified honeycomb and Prunella vulgaris were classified into the heat-sensitive component extraction group. They were extracted with 50% ethanol at 40℃ using dynamic countercurrent extraction to protect the flavonoid components. The ethanol was recovered from the effluent under reduced pressure, and the concentrate was freeze-dried to obtain a yellow-brown extract.

[0032] S5. Combine the three extracts, add β-cyclodextrin and trehalose in a mass ratio of 1:1 as protectants, spray dry to make dry powder, and compress into tablets or fill capsules.

[0033] Table 1 Key process control points in the preparation process Process advantages description 1. High triterpene retention technology: Supercritical CO2 extraction replaces traditional alcohol extraction, increasing the extraction rate of ganoderic acid B from 58% to 92.5%. Optimized entrainer (ethanol-water 7:3) improves the recovery rate of polar triterpenes by 37%.

[0034] 2. Polysaccharide activity protection technology: small molecule impurities (pigments, etc.) are removed by ceramic membrane separation, and the β-glucan helical structure is maintained by low-temperature spray drying (instantaneous heating <3 seconds).

[0035] 3. Precise control of toxic components: The exposed honeycomb double-stage supercritical detoxification first removes honeycomb oil, then extracts active ingredients, and GC-FID controls honeycomb oil residue in real time.

[0036] 4. Heat-sensitive component protection solution: Countercurrent extraction temperature ≤40℃, flavonoid retention rate is increased by 42% compared with conventional reflux extraction. Freeze-drying replaces vacuum drying to avoid oxidation of phenolic acid components.

[0037] This process achieves the following results through targeted extraction technology, activity protection strategy, and precise toxicity control: triterpenoid retention rate ≥95%; polysaccharide yield ≥15%; flavonoid degradation rate ≤5%; and toxicity compliance rate 100%.

[0038] Example 2 differs from Example 1 in that it contains: 20 parts of Ganoderma lucidum spore powder, 15 parts of Cremastra appendiculata, 15 parts of Scutellaria barbata, 25 parts of Hedyotis diffusa, 10 parts of detoxified propolis, 25 parts of Prunella vulgaris, 15 parts of Evodia rutaecarpa, and 20 parts of Echinops latifolius.

[0039] Example 3 differs from Example 1 in that it contains 35 parts of Ganoderma lucidum spore powder, 20 parts of Cremastra appendiculata, 20 parts of Scutellaria barbata, 30 parts of Hedyotis diffusa, 12 parts of detoxified propolis, 30 parts of Prunella vulgaris, 20 parts of Evodia rutaecarpa, and 25 parts of Echinops latifolius.

[0040] Efficacy verification: In vitro: IC50 on MCF-7 cells 50 =78.4μg / mL, an increase of 38.6% compared to the original formula; In vivo: Tumor inhibition rate in nude mice was 61.2% (P<0.01), CD4 + / CD8 + The ratio increased by 1.8 times; Toxicity reduction: Combined use of 5-FU reduced the incidence of myelosuppression from 45% to 18%.

[0041] Clinical value positioning: This compound has a significant effect on triple-negative breast cancer (TNBC): the tumor inhibition rate in the xenograft model is 61.2%; the number of lung metastatic nodules is reduced by 73.5%; its core mechanism lies in the simultaneous inhibition of EMT (downregulation of Vimentin by 68%) and maintenance of stemness (reducing the proportion of ALDH+ cells to 4.1%).

[0042] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. A traditional Chinese medicine compound preparation for treating breast cancer, characterized in that... It is made from the following raw materials in parts by weight: 25-35 parts of Ganoderma lucidum spore powder, 10-20 parts of Cremastra appendiculata, 10-20 parts of Scutellaria barbata, 20-30 parts of Hedyotis diffusa, 8-12 parts of detoxified propolis, 20-30 parts of Prunella vulgaris, 10-20 parts of Evodia rutaecarpa, and 15-25 parts of Echinops latifolius.

2. The traditional Chinese medicine compound preparation for treating breast cancer according to claim 1, characterized in that... It is made from the following raw materials in parts by weight: 20 parts of Ganoderma lucidum spore powder, 15 parts of Cremastra appendiculata, 15 parts of Scutellaria barbata, 25 parts of Hedyotis diffusa, 10 parts of detoxified propolis, 25 parts of Prunella vulgaris, 15 parts of Evodia rutaecarpa and 20 parts of Echinops latifolius.

3. The method for preparing a traditional Chinese medicine compound preparation for breast cancer according to claim 2, characterized in that, Includes the following steps: S1. Ganoderma lucidum spore powder, Pseudobulbus Cremastrae and Scutellaria barbata were classified as fat-soluble components extraction group. Supercritical CO2 extraction was used. Triterpenoid components were collected in separation vessel I at a pressure of 10 MPa and a temperature of 60℃, and alkaloid components were collected in separation vessel II at a pressure of 5 MPa and a temperature of 35℃. The products from the two separation vessels were combined and vacuum dried to obtain a brownish-yellow fat-soluble extract. S2. The white flower snake tongue grass, Yuzhizi and Echinopsis lanceolata were classified into the water-soluble component extraction group. They were extracted with hot water at 90℃ for 2 hours with a material-liquid ratio of 1:

12. The extract was separated and enriched with polysaccharides through a ceramic membrane. The retentate was concentrated under reduced pressure to a relative density of 1.25 and spray-dried to obtain white polysaccharide powder. S3. Detoxification treatment of exposed honeycomb: Take dried exposed honeycomb medicinal material, crush it into 40 mesh using a pulverizer, and then put it into a supercritical CO2 extraction device. Under the conditions of constant pressure 35 MPa and constant temperature 45℃, dynamic circulation extraction is carried out at a CO2 flow rate of 25 liters per hour for 120 minutes to fully dissolve the nephrotoxic honeycomb oil components in the medicinal material and obtain detoxified exposed honeycomb. S4. Detoxified honeycomb and Prunella vulgaris were classified into the heat-sensitive component extraction group. They were extracted with 50% ethanol at 40℃ using dynamic countercurrent extraction to protect the flavonoid components. The ethanol was recovered under reduced pressure from the effluent, and the concentrate was freeze-dried to obtain a yellow-brown extract. S5. Combine the three extracts, add β-cyclodextrin and trehalose as protectants, spray dry to make dry powder, compress into tablets or fill capsules.

4. The preparation method of a traditional Chinese medicine compound preparation for treating breast cancer according to claim 3, characterized in that: In S1, the supercritical CO2 extraction pressure is 35 MPa, the temperature is 45 °C, and the entrainer is a 7:3 ratio of ethanol to water.

5. The preparation method of a traditional Chinese medicine compound preparation for treating breast cancer according to claim 4, characterized in that: In step S2, the filtration accuracy of the ceramic membrane is 10 kDa.

6. The method for preparing a traditional Chinese medicine compound preparation for breast cancer according to claim 5, characterized in that: In S3, the detoxified honeycomb needs to be tested by gas chromatography to confirm that the residual honeycomb oil content is less than 100 ppm.

7. The preparation method of a traditional Chinese medicine compound preparation for breast cancer according to claim 6, characterized in that: In step S5, the mass ratio of β-cyclodextrin to trehalose is 1:

1.

8. The use of the compound preparation according to any one of claims 1-7 in the preparation of a drug that enhances the anti-breast cancer activity of 5-fluorouracil.

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