Traditional Chinese medicine targeted multilayer tablet for resisting uterine cancer and preparation method of traditional Chinese medicine targeted multilayer tablet

Abstract

The invention discloses an anti-uterine cancer traditional Chinese medicine targeted multilayer tablet and a preparation method thereof, and is characterized in that the anti-uterine cancer traditional Chinese medicine targeted multilayer tablet is prepared from the following components by weight: 150-250g of edible tulip, 75-90g of toad skin, 150-200g of centipede, 80-120g of astragalus membranaceus, 100-150g of fructus viticis, 50-80g of ganoderma lucidum spore powder, 50-60g of sculellaria barbata, 100-150g of semen coicis, 20-40g of liquorice and 60-100g of oldenlandia diffusa. The medicine effect can be improved, and growth, metastasis and diffusion of tumors can be effectively inhibited.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, and in particular to a targeted multilayer tablet of traditional Chinese medicine for treating uterine cancer and its preparation method. Background Technology

[0002] Uterine cancer is divided into two types: bleeding and non-bleeding. Non-bleeding cancer is characterized by a localized abnormal increase in tumor size; bleeding cancer is characterized by cancer of the uterine myometrium, cervix, or endometrium. In the early stages, there is no bleeding or only a small amount of bleeding. In the middle stages, the bleeding is slightly more, with intermittent bleeding. In the late stages, the bleeding is heavy, irregular, and contains a large amount of clots. In severe cases, the uterus may ulcerate and become necrotic tissue. Metastatic cancer can spread from the lower abdomen, abdomen, heart, liver, lungs, and head to the whole body, with several metastatic tumors in the neck, armpits, and groin. This can consume a large amount of nutrients from the body and ultimately lead to death.

[0003] Currently, traditional Chinese medicine (TCM) treatments for uterine tumors have several shortcomings: firstly, their efficacy is not significant; secondly, their effects are relatively slow; and thirdly, they cannot address both the symptoms and the root cause. Many uterine cancer patients experience reduced survival time because medications cannot effectively control tumor growth, metastasis, and spread, or because the cancer recurs after discontinuing medication. Summary of the Invention

[0004] The purpose of this invention is to provide a targeted multilayer tablet of traditional Chinese medicine for treating uterine cancer and its preparation method, which can improve efficacy and effectively inhibit tumor growth, metastasis and spread.

[0005] The above-mentioned technical objective of the present invention is achieved through the following technical solution: A targeted multilayer tablet of traditional Chinese medicine for treating uterine cancer is characterized by being made from the following components in the following weight proportions: 150-250g of Pseudobulbus Cremastrae, 75-90g of Toad Skin, 150-200g of Centipede, 80-120g of Astragalus, 100-150g of Vitex trifolia, 50-80g of Ganoderma lucidum spore powder, 50-60g of Scutellaria barbata, 100-150g of Coix lacryma-jobi, 20-40g of Glycyrrhiza uralensis, and 60-100g of Hedyotis diffusa.

[0006] Further: It is made from the following components in the following weight proportions: 200g of Pseudobulbus Cremastrae, 80g of toad skin, 150g of centipede, 100g of Astragalus membranaceus, 120g of Vitex trifolia, 60g of Ganoderma lucidum spore powder, 50g of Scutellaria barbata, 100g of Coix lacryma-jobi, 30g of Glycyrrhiza uralensis, and 80g of Hedyotis diffusa.

[0007] This invention also provides a method for preparing a multi-layered targeted tablet of traditional Chinese medicine for treating uterine cancer, comprising the following steps: Step 1: Multi-level extraction Fat-soluble components: often extracted with supercritical CO2 at 28 MPa and 45°C, and used in combination with 5% ethyl acetate as an entrainer; Water-soluble components: extracted with subcritical water at 120℃ and 5MPa and dynamically circulated 3 times; Step 2, preparation of targeted nanoparticles: The *Cremastra appendiculata* was processed into nanoparticles using a thin film-ultrasound method. Then, *Coix lacryma-jobi* was added to an emulsifier and homogenized under high pressure to prepare *Coix lacryma-jobi* oil nanoemulsion. PLGA, colchicine, and folic acid-PEG3350 were dissolved in dichloromethane and injected into an aqueous phase containing 0.5% F68. The mixture was ultrasonically processed using a probe, concentrated by ultrafiltration, and then freeze-dried to obtain nanoparticles with a particle size of 189±7nm. Step 3: Multi-layer sheet forming: Immediate-release layer: Astragalus polysaccharide freeze-dried powder and Scutellaria barbata flavonoids are mixed evenly and granulated by roller pressing. Sustained-release layer: Mix the Pseudobulbus Cremastrae nanoparticles and Ganoderma lucidum polysaccharides evenly, then add 5% HPMC binder and wet granulate; Enteric coating: Centipede polypeptides were loaded onto sucrose microspheres and coated with a bottom coating after setting the working parameters of the fluidized bed; Tableting: The tablets are sequentially filled with a sustained-release layer, enteric-coated microcapsules, and an immediate-release layer, and the pressure of the tablet press is controlled at 15 kN for tableting.

[0008] Furthermore: In step two, the emulsifier is prepared in a ratio of Labrasol:TPGS = 3:1.

[0009] Furthermore: In step three, the hardness of dry granulation is 50-60N.

[0010] Furthermore: In step three, the rolling pressure is 8 MPa.

[0011] Furthermore: In step three, the coating parameters of the fluidized bed are: inlet air temperature 45±1℃, atomization pressure 0.8MPa, and coating weight gain 12±0.5%.

[0012] In summary, the present invention has the following beneficial effects: Firstly, this invention can improve drug efficacy and effectively inhibit tumor growth, metastasis, and spread; Secondly, this invention induces apoptosis of cancer cells by allowing the nanoparticles of *Cremastra appendiculata* to accumulate within the tumor, while simultaneously inhibiting the VEGF pathway and microvascular density through centipede polypeptides. Attached Figure Description

[0013] Figure 1 This is a process flow diagram of the present invention. Detailed Implementation

[0014] The present invention will be further described in detail below with reference to the accompanying drawings.

[0015] In the description of this invention, it should be understood that the terms "upper", "lower", "left", "right", "front", "rear", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0016] Example, refer to Figure 1 A multi-layered Chinese medicine tablet for treating uterine cancer is made from the following components in the indicated weight proportions: 200g of Pseudobulbus Cremastrae, 80g of Toad Skin, 150g of Centipede, 100g of Astragalus, 120g of Vitex trifolia, 60g of Ganoderma lucidum spore powder, 50g of Scutellaria barbata, 100g of Coix lacryma-jobi, 30g of Glycyrrhiza uralensis, and 80g of Hedyotis diffusa.

[0017] A method for preparing a multi-layered targeted tablet of traditional Chinese medicine for treating uterine cancer includes the following steps: Step 1: Multi-level extraction Fat-soluble components: often extracted with supercritical CO2 at 28 MPa and 45°C, and used in combination with 5% ethyl acetate as an entrainer; Water-soluble components: extracted with subcritical water at 120℃ and 5MPa and dynamically circulated 3 times; Step 2, preparation of targeted nanoparticles: The *Cremastra appendiculata* was processed into nanoparticles using a thin film-ultrasound method. Then, *Coix lacryma-jobi* was added to an emulsifier prepared by a ratio of Labrasol:TPGS=3:1 and homogenized under high pressure to prepare *Coix lacryma-jobi* oil nanoemulsion. PLGA, colchicine, and folic acid-PEG3350 were dissolved in dichloromethane and injected into an aqueous phase containing 0.5% F68. The mixture was ultrasonically processed using a probe, concentrated by ultrafiltration, and then freeze-dried to obtain nanoparticles with a particle size of 189±7nm. Step 3: Multi-layer sheet forming: Immediate-release layer: Astragalus polysaccharide freeze-dried powder and Scutellaria barbata flavonoids are mixed evenly and dry granulation is achieved by applying 8 MPa pressure through roller pressing, and the hardness of the granules is controlled to be 50-60 N. Sustained-release layer: Mix the Pseudobulbus Cremastrae nanoparticles and Ganoderma lucidum polysaccharides evenly, then add 5% HPMC binder and wet granulate; Enteric coating: Centipede polypeptides were loaded onto sucrose microcapsules, and the fluidized bed operating parameters were set as follows: inlet air temperature 45±1℃ and atomization pressure 0.8MPa, followed by bottom spray coating to achieve a coating weight gain of 12±0.5%. Tableting: The tablets are sequentially filled with a sustained-release layer, enteric-coated microcapsules, and an immediate-release layer, and the pressure of the tablet press is controlled at 15 kN for tableting.

[0018] Prescription composition and processing techniques Setting up experiments Model: BALB / c nude mouse uterine cancer xenograft (HeLa cell line, subcutaneous inoculation) Grouping (n=10): Experimental group: Multilayer tablets of this invention (daily gavage, equivalent human dose 20mg / kg) Control group 1: Traditional decoction (same dosage); Control group 2: Cisplatin (3 mg / kg, intraperitoneal injection); Control group 3: Blank excipients; Treatment duration: 21 days; Evaluation indicators: Tumor Inhibition Rate (TGI) = (1 - Tumor weight in experimental group / Tumor weight in control group) × 100% Immune markers: CD8+ / Treg ratio detected by flow cytometry.

[0019] Experimental data Efficiency Enhancement Mechanism Direct killing: Pseudobulbus Cremastrae nanoparticles accumulate in tumors, induce apoptosis of cancer cells, and increase Caspase-3 activity; Immune synergy: Ganoderma lucidum polysaccharide-zinc polymer activates dendritic cells and increases the proportion of CD83+ cells; Anti-angiogenesis: Centipede polypeptide inhibits the VEGF pathway and reduces microvascular density.

[0020] Basis for the bioavailability of centipede polypeptides: Traditional problem: The degradation rate of peptides in gastric acid is >89% (bioavailability of the untreated group is 11%).

[0021] Technical countermeasures: Enteric coating (EUDRAGIT® L100, 12% weight gain), dissolves at pH ≥ 6.8; Enzymatic purification: removal of <5kDa sensitizing peptides and >15kDa neurotoxins; Results: Bioavailability reached 82.1% (intestinal absorption rate was determined by LC-MS / MS). The in vivo antitumor activity was increased by 7.3 times (compared to uncoated peptides).

[0022] 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 inventive modifications to this embodiment as needed, but as long as they are within the scope of the claims of the present invention, they are protected by patent law.

Claims

1. A multi-layered targeted traditional Chinese medicine tablet for treating uterine cancer, characterized in that, It is made from the following components in the following weight proportions: 150-250g of Pseudobulbus Cremastrae, 75-90g of Toad Skin, 150-200g of Centipede, 80-120g of Astragalus, 100-150g of Vitex trifolia, 50-80g of Ganoderma lucidum spore powder, 50-60g of Scutellaria barbata, 100-150g of Coix lacryma-jobi, 20-40g of Glycyrrhiza uralensis, and 60-100g of Hedyotis diffusa.

2. The targeted multi-layered tablet for treating uterine cancer according to claim 1, characterized in that: It is made from the following ingredients in the following weight proportions: 200g of Pseudobulbus Cremastrae, 80g of toad skin, 150g of centipede, 100g of Astragalus membranaceus, 120g of Vitex trifolia, 60g of Ganoderma lucidum spore powder, 50g of Scutellaria barbata, 100g of Coix lacryma-jobi, 30g of Glycyrrhiza uralensis, and 80g of Hedyotis diffusa.

3. The method for preparing a multi-layered targeted traditional Chinese medicine tablet for uterine cancer according to claim 1, characterized in that, Includes the following steps: Step 1: Multi-level extraction Fat-soluble components: often extracted with supercritical CO2 at 28 MPa and 45°C, and used in combination with 5% ethyl acetate as an entrainer; Water-soluble components: extracted with subcritical water at 120℃ and 5MPa and dynamically circulated 3 times; Step 2, preparation of targeted nanoparticles: The *Cremastra appendiculata* was processed into nanoparticles using a thin film-ultrasound method. Then, *Coix lacryma-jobi* was added to an emulsifier and homogenized under high pressure to prepare *Coix lacryma-jobi* oil nanoemulsion. PLGA, colchicine, and folic acid-PEG3350 were dissolved in dichloromethane and injected into an aqueous phase containing 0.5% F68. The mixture was ultrasonically processed using a probe, concentrated by ultrafiltration, and then freeze-dried to obtain nanoparticles with a particle size of 189±7nm. Step 3: Multi-layer sheet forming: Immediate-release layer: Astragalus polysaccharide freeze-dried powder and Scutellaria barbata flavonoids are mixed evenly and granulated by roller pressing. Sustained-release layer: Mix the Pseudobulbus Cremastrae nanoparticles and Ganoderma lucidum polysaccharides evenly, then add 5% HPMC binder and wet granulate; Enteric coating: Centipede polypeptides were loaded onto sucrose microspheres and coated with a bottom coating after setting the working parameters of the fluidized bed; Tableting: The tablets are sequentially filled with a sustained-release layer, enteric-coated microcapsules, and an immediate-release layer, and the pressure of the tablet press is controlled at 15 kN for tableting.

4. The method for preparing a multi-layered targeted traditional Chinese medicine tablet for uterine cancer according to claim 3, characterized in that: In step two, the emulsifier is prepared in a ratio of Labrasol:TPGS = 3:

1.

5. The method for preparing a multi-layered targeted traditional Chinese medicine tablet for uterine cancer according to claim 3, characterized in that: In step three, the hardness of dry granulation is 50-60 N.

6. The method for preparing a multi-layered targeted traditional Chinese medicine tablet for uterine cancer according to claim 3, characterized in that: In step three, the rolling pressure is 8 MPa.

7. The method for preparing a multi-layered targeted traditional Chinese medicine tablet for uterine cancer according to claim 3, characterized in that: In step three, the coating parameters of the fluidized bed are: inlet air temperature 45±1℃, atomization pressure 0.8MPa, and coating weight gain 12±0.5%.

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