Pharmaceutical composition for treating colon cancer

Abstract

The invention relates to the technical field of medicines, and particularly discloses a pharmaceutical composition for treating colon cancer, which is prepared from 20 to 40 parts of astragalus polysaccharide extract, 15 to 30 parts of ginsenoside Rg3 derivative, 10 to 20 parts of ganoderic acid G nanocrystal, 5 to 15 parts of angelica volatile oil microemulsion, 5 to 10 parts of matrine solid dispersion and 10 to 20 parts of auxiliary components, according to the invention, astragalus polysaccharide (immune activation), ginsenoside Rg3 liposome (anti-angiogenesis), ganoderic acid G nanocrystals (microenvironment regulation), angelica volatile oil microemulsion (metastasis inhibition) and matrine solid dispersion (apoptosis induction) are integrated through a heterogeneous system to form a natural pharmaceutical composition with four-channel synergistic effect of'immunity-blood vessel-metastasis-apoptosis'. The treatment effect is greatly improved, and the defects that a traditional natural extract medicine composition for treating colon cancer is poor in effect and insufficient in drug resistance are overcome.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and in particular, to a pharmaceutical composition for treating colon cancer. Background Art

[0002] Colon cancer is a malignant tumor that occurs in the mucosal epithelium of the colon (the main part of the large intestine), and is prone to occur at the junction of the rectum and the sigmoid colon, with adenocarcinoma being the most common. Its incidence is closely related to genetic factors (such as familial adenomatous polyposis, hereditary non-polyposis colorectal cancer), poor eating habits (high-fat and low-fiber diet, excessive intake of processed meat), chronic intestinal inflammation (such as ulcerative colitis), malignant transformation of intestinal polyps, etc., and it mainly occurs in the middle-aged and elderly population.

[0003] For the treatment of colon cancer, the existing treatment methods are mainly divided into surgical treatment and drug treatment. However, there are still many deficiencies in the existing pharmaceutical compositions for treating colon cancer. There are problems of drug resistance for chemotherapy, targeted and immunotherapeutic drugs. Targeted drugs have a narrow indication due to tumor heterogeneity, the synergistic mechanism of combined drugs is unclear and may produce antagonism or toxicity superposition. In terms of safety, chemotherapy drugs have significant systemic toxicity, and immunotherapy is prone to trigger autoimmune reactions, affecting the tolerance and compliance of patients, and is not suitable for the elderly. Existing natural extract drugs are safe, but they have problems such as unclear composition, single target, and poor bioavailability, resulting in poor treatment effects.

[0004] Therefore, it is necessary to design a pharmaceutical composition for treating colon cancer to solve the problems of unclear composition, single target, and poor bioavailability of the existing pharmaceutical compositions for treating colon cancer extracted from natural sources. Summary of the Invention

[0005] In view of this, the present invention provides a pharmaceutical composition for treating colon cancer, aiming to solve the problems of unclear treatment composition, single target, insufficient drug resistance, and poor bioavailability of the existing pharmaceutical compositions for treating colon cancer extracted from natural sources.

[0006] On the one hand, the present invention provides a pharmaceutical composition for treating colon cancer, comprising the following components in parts by mass:

[0007] 20 - 40 parts of astragalus polysaccharide extract, 15 - 30 parts of ginsenoside Rg3 derivative, 10 - 20 parts of ganoderic acid G nanocrystals, 5 - 15 parts of angelica volatile oil microemulsion, 5 - 10 parts of matrine solid dispersion, and 10 - 20 parts of auxiliary components.

[0008] Furthermore, the auxiliary components are mixed from a pH-responsive carrier material, an antioxidant, and an osmotic pressure regulator according to a mass ratio of 15:4:9.

[0009] Furthermore, the preparation method of the astragalus polysaccharide extract is as follows: After ultrasonic extraction of astragalus decoction pieces, the supernatant is obtained by centrifugation, the supernatant is concentrated to 1 g / mL, three times the volume of ethanol is added for drying, and the astragalus polysaccharide extract is obtained after purification.

[0010] Furthermore, the preparation method of the ginsenoside Rg3 derivative is as follows: Ginsenoside Rg3 and distearoyl phosphatidylcholine are co-dissolved in a chloroform-methanol mixed solvent, and the solvent is evaporated to dryness in a water bath until a lipid film is formed. Subsequently, the residual solvent is blown dry, and phosphate buffer solution is added for ultrasonic treatment until the film is completely hydrated to obtain a dispersion. The dispersion is extruded through a polycarbonate membrane to obtain the ginsenoside Rg3 derivative.

[0011] Furthermore, the preparation method of ganoderic acid G nanocrystals is as follows: The ethanol extract of ganoderma spores is dissolved in a methanol-water mixed solvent, and after separation by high performance liquid chromatography (HPLC), it is eluted, concentrated and dried in sequence to obtain ganoderic acid G crystals. After the ganoderic acid G crystals are dissolved in absolute ethanol, 0.5% stabilizer is added to obtain a primary suspension. The primary suspension is subjected to high-pressure circulation treatment and then freeze-dried to obtain the ganoderic acid G nanocrystals.

[0012] Furthermore, the preparation method of the angelica volatile oil microemulsion is as follows: Ligustilide, Tween 80, and glycerol are mixed in a ratio of 1:3:2, and dropped into phosphate buffer solution with a pH of 6.8, and the angelica volatile oil microemulsion is obtained after ultrasonic emulsification.

[0013] Furthermore, the preparation method of the matrine solid dispersion is as follows: Matrine and polyethylene glycol 6000 are dissolved in ethanol in a ratio of 1:5, and the matrine solid dispersion is obtained after spray drying.

[0014] On the other hand, the present invention also provides a preparation method of the pharmaceutical composition for treating colon cancer, comprising the following preparation steps:

[0015] The astragalus polysaccharide extract, ginsenoside Rg3 derivative, ganoderic acid G nanocrystals, angelica volatile oil microemulsion, matrine solid dispersion and auxiliary components are stirred at room temperature to obtain the pharmaceutical composition for treating colon cancer.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: After natural ingredients such as astragalus polysaccharide, ginsenoside Rg3 derivative, ganoderic acid G, angelica volatile oil, and matrine are transformed by nanocrystal, microemulsion, and solid dispersion technologies, a four-pathway synergistic system of "immune activation - anti-angiogenesis - metastasis inhibition - apoptosis induction" is constructed, breaking through the limitations of traditional Chinese medicine components being vague and having a single target, and significantly enhancing the inhibitory effect on drug-resistant colon cancer such as KRAS mutant type and MSS / pMMR type; at the same time, a pH-responsive chitosan carrier is used to construct a targeted delivery system, greatly improving the bioavailability of natural ingredients, reducing the irritation to normal intestinal mucosa, and reducing diarrhea and myelosuppression. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] By reading the following detailed description of the preferred embodiments, various other advantages and benefits will become clear to those of ordinary skill in the art. The drawings are only for the purpose of showing the preferred embodiments and are not considered to be a limitation of the present invention. Moreover, throughout the drawings, the same reference numerals are used to represent the same components. In the drawings:

[0018] Figure 1 It is a flowchart of the preparation method of the pharmaceutical composition for treating colon cancer provided by the embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0019] The exemplary embodiments of the present disclosure will be described in more detail below with reference to the drawings. Although the exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided so that the present disclosure can be more thoroughly understood and the scope of the present disclosure can be completely conveyed to those skilled in the art. It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other. The present invention will be described in detail below with reference to the drawings and in conjunction with the embodiments.

[0020] After natural ingredients such as astragalus polysaccharide, ginsenoside Rg3 derivative, ganoderic acid G, angelica volatile oil, and matrine are transformed by nanocrystal, microemulsion, and solid dispersion technologies, a four-pathway synergistic system of "immune activation - anti-angiogenesis - metastasis inhibition - apoptosis induction" is constructed, breaking through the limitations of traditional Chinese medicine components being vague and having a single target, and significantly enhancing the inhibitory effect on drug-resistant colon cancer such as KRAS mutant type and MSS / pMMR type; a pH-responsive chitosan carrier is used to construct a targeted delivery system, greatly improving the bioavailability of natural ingredients, reducing the irritation to normal intestinal mucosa, and reducing diarrhea and myelosuppression.

[0021] On the one hand, as Figure 1 shown, in some embodiments of the present application, a pharmaceutical composition for treating colon cancer includes the following components in parts by mass:

[0022] 20 - 40 parts of astragalus polysaccharide extract, 15 - 30 parts of ginsenoside Rg3 derivative, 10 - 20 parts of ganoderic acid G nanocrystal, 5 - 15 parts of angelica volatile oil microemulsion, 5 - 10 parts of matrine solid dispersion, and 10 - 20 parts of auxiliary components.

[0023] Preferably, it is 30 - 40 parts of astragalus polysaccharide extract, 20 - 30 parts of ginsenoside Rg3 derivative, 15 - 20 parts of ganoderic acid G nanocrystal, 10 - 15 parts of angelica volatile oil microemulsion, 8 - 10 parts of matrine solid dispersion, and 15 - 20 parts of auxiliary components.

[0024] More preferably, it is 30 parts of astragalus polysaccharide extract, 20 parts of ginsenoside Rg3 derivative, 15 parts of ganoderic acid G nanocrystal, 10 parts of angelica volatile oil microemulsion, 8 parts of matrine solid dispersion, and 15 parts of auxiliary components.

[0025] It can be understood that the astragalus polysaccharide in the present invention reverses the immunosuppression of MDSCs by activating the cGAS - STING pathway, synergistically blocks angiogenesis mediated by VEGF / VEGFR2 with ginsenoside Rg3, and reduces the nutrient supply of drug - resistant cells.

[0026] It can be understood that ganoderic acid G in the present invention inhibits TGF - β1 secreted by CAFs, relieves its inhibitory effect on T cells. At the same time, matrine induces apoptosis of chemotherapy - resistant cells (such as HCT116 / 5 - FU) by up - regulating the Bax / Bcl - 2 ratio, solving the defect of insufficient anti - drug resistance of single components;

[0027] It can be understood that the angelica volatile oil in the present invention can target and inhibit the adhesion molecules between tumor cells and endothelial cells, block the key steps of liver metastasis, and fill the blank of the weak effect of existing natural drugs on metastatic foci.

[0028] It can be understood that the present invention constructs a "four - pathway synergistic system of immune activation - anti - angiogenesis - metastasis inhibition - apoptosis induction" by transforming natural components such as astragalus polysaccharide, ginsenoside Rg3 derivative, ganoderic acid G, angelica volatile oil, and matrine through nanocrystal, microemulsion, and solid dispersion technologies, breaking through the limitations of traditional Chinese medicine components being fuzzy and having single targets, and significantly enhancing the inhibitory effect on drug - resistant colon cancer such as KRAS - mutant type and MSS / pMMR type; a targeted delivery system is constructed using a pH - responsive chitosan carrier, greatly improving the bioavailability of natural components, reducing the irritation to normal intestinal mucosa, and reducing diarrhea and myelosuppression.

[0029] In some embodiments of the present application, the auxiliary components are mixed by a pH - responsive carrier material, an antioxidant, and an osmotic pressure regulator according to a mass ratio of 15:4:9.

[0030] Specifically, the pH-responsive carrier material is preferably carboxymethyl chitosan, the antioxidant is preferably vitamin E succinate, and the osmotic pressure regulator is preferably sodium chloride; the degree of deacetylation of the carboxymethyl chitosan is ≥90%.

[0031] It can be understood that carboxymethyl chitosan, as a pH-responsive carrier, can stably load natural active ingredients and target the release in the acidic environment of the colon. Vitamin E succinate effectively inhibits the oxidation of polyphenol extracts at a low dose, and sodium chloride precisely adjusts the osmotic pressure to the physiological safety range of 290-300 mOsm / kg to avoid irritation to the intestinal mucosa. This specific ratio is not disclosed in the existing natural medicine compositions, and the stability and targeted delivery efficiency of the preparation are improved through the synergistic effect among the components.

[0032] It can be understood that the pH-responsive carrier material, antioxidant, and osmotic pressure regulator are mixed in a mass ratio of 15:4:9, which not only ensures the stable loading and targeted delivery of the active ingredients by the carrier material but also inhibits the oxidative degradation of natural ingredients by a low-dose antioxidant. At the same time, sodium chloride adjusts the osmotic pressure of the system to the physiologically compatible range to avoid the risk of hemolysis or cell damage.

[0033] In some embodiments of the present application, the preparation method of the astragalus polysaccharide extract is as follows: After ultrasonic extraction of astragalus decoction pieces, the supernatant is taken by centrifugation, the supernatant is concentrated to 1 g / mL, three times the volume of ethanol is added for drying, and the astragalus polysaccharide extract is obtained after purification.

[0034] Specifically, the parameters of the ultrasonic extraction are preferably: power 300 W, temperature 60 °C, time 40 min; the ethanol is preferably a 95% ethanol solution, the drying is preferably vacuum drying, and the purification is specifically carried out by purification using a DEAE-cellulose column.

[0035] Specifically, the finally prepared astragalus polysaccharide extract has a molecular weight of 5-15 kDa, a purity of ≥90%, is rich in α-1,4-glucan and β-1,3-glucan, and has an immune-enhancing effect of activating dendritic cells (DCs) and promoting the secretion of IL-12.

[0036] In some embodiments of the present application, the preparation method of the ginsenoside Rg3 derivative is as follows: Ginsenoside Rg3 and distearoyl phosphatidylcholine are co-dissolved in a chloroform-methanol mixed solvent, evaporated to dryness in a water bath until a lipid-like film is formed, and then the residual solvent is blown dry, and phosphate buffer solution is added for ultrasonic treatment until the film is completely hydrated to obtain a dispersion liquid. The dispersion liquid is extruded through a polycarbonate membrane to obtain the ginsenoside Rg3 derivative.

[0037] Specifically, the mass ratio of ginsenoside Rg3 to distearoyl phosphatidylcholine is 1:5; the volume ratio of chloroform to methanol in the chloroform-methanol mixed solvent is 2:1; the temperature for evaporation to dryness in a water bath is preferably 40°C, and the rotation speed is preferably 80 rpm; the phosphate buffer solution is a phosphate buffer solution with a pH of 7.4 containing 0.9% sodium chloride.

[0038] Specifically, the drying of the residual solvent is specifically carried out by drying with nitrogen for 30 minutes; the ultrasonic treatment is specifically carried out in a 37°C water bath with a power of 200 W, and it is paused for 15 seconds every 30 seconds of treatment.

[0039] Specifically, when the dispersion is extruded through a polycarbonate membrane again, the dispersion is passed through an extruder equipped with a polycarbonate membrane with a pore size of 100 nm and reciprocally extruded 10 times under a pressure of 100 bar, and the extruded liquid is collected to obtain a stable ginsenoside Rg3 derivative.

[0040] It can be understood that the ginsenoside Rg3 derivative prepared by the enzymatic hydrolysis method can specifically inhibit the phosphorylation of tumor cell VEGFR2 and the protein stability of HIF-1α, blocking angiogenesis and hypoxia adaptation.

[0041] In some embodiments of the present application, the preparation method of ganoderic acid G nanocrystals is as follows: dissolve the ethanol extract of ganoderma spore powder in a methanol-water mixed solvent, separate by high performance liquid chromatography (HPLC), and then carry out elution, concentration and drying in sequence to obtain ganoderic acid G crystals. After dissolving the ganoderic acid G crystals in absolute ethanol, add 0.5% of a stabilizer to obtain a primary suspension, and subject the primary suspension to high-pressure circulation treatment and then freeze-dry to obtain the ganoderic acid G nanocrystals.

[0042] Specifically, the elution, concentration and drying are specifically as follows: separate by high performance liquid chromatography (HPLC), collect the elution peak with a retention time of 28 - 30 minutes at a wavelength of 254 nm, and obtain ganoderic acid G crystals with a purity of ≥98% through vacuum concentration and freeze-drying.

[0043] Specifically, when dissolving ganoderic acid G crystals in absolute ethanol, 5 ml of absolute ethanol is required for every 100 mg of ganoderic acid G crystals.

[0044] Specifically, the high-pressure circulation treatment is specifically carried out 5 times under a pressure of 100 MPa using a high-pressure homogenizer.

[0045] Specifically, the stabilizer is poloxamer 188, and the addition amount is 0.5% of the solution volume; the volume ratio of methanol to water in the methanol-water mixed solvent is 4:1.

[0046] It is understandable that using high-pressure homogenization technology to prepare Ganoderenic acid G nanocrystals (particle size 50 - 80 nm) dispersed in anhydrous ethanol can targetedly inhibit the NF-κB pathway and tumor-associated fibroblasts (CAFs) from secreting TGF-β, reversing the immunosuppressive microenvironment.

[0047] In some embodiments of the present application, the preparation method of the Angelica sinensis volatile oil microemulsion is as follows: Ligustilide, Tween 80, and glycerol are mixed in a ratio of 1:3:2, and then dropped into a phosphate buffer solution with a pH of 6.8, and the Angelica sinensis volatile oil microemulsion is obtained after ultrasonic emulsification; the ultrasonic emulsification time is preferably 30 minutes.

[0048] It is understandable that the O / W type microemulsion prepared from the Angelica sinensis ether extract, Tween 80, and glycerol can block tumor cell migration and liver metastasis by inhibiting the CXCR4 / CXCL12 axis;

[0049] In some embodiments of the present application, the preparation method of the matrine solid dispersion is as follows: Matrine and polyethylene glycol 6000 (PEG6000) are dissolved in ethanol in a ratio of 1:5, and the matrine solid dispersion is obtained after spray drying; the inlet temperature of the spray drying is preferably 180°C, and the flow rate is preferably 5 ml / min.

[0050] It is understandable that the matrine solid dispersion prepared by using PEG6000 as a carrier and the solvent-spray drying method can selectively induce the mitochondrial apoptosis pathway of p53 wild-type colon cancer cells and simultaneously enhance the infiltration of CD8+ T cells;

[0051] On the other hand, some embodiments of the present invention also provide a preparation method of the drug composition for treating colon cancer, including the following preparation steps:

[0052] The Astragalus polysaccharide extract, Ginsenoside Rg3 derivative, Ganoderenic acid G nanocrystals, Angelica sinensis volatile oil microemulsion, matrine solid dispersion, and auxiliary components are stirred at room temperature to obtain the drug composition for treating colon cancer; the time of the room temperature stirring is preferably 2 hours.

[0053] It is understandable that in the preparation process of the present invention, through technologies such as enzymatic transformation and high-pressure homogenization, the water-soluble modification of lipophilic components and the precise control of particle size are realized, solving the defects of poor stability and weak targeting of natural drugs, and the raw materials are easily available and the cost is low (70% lower than targeted drugs). At the same time, by regulating the AMPK / mTOR pathway and the caspase apoptosis pathway, it has both direct killing and immune activation dual effects, making up for the blank of the insufficient anti-metastasis and anti-stem cell capabilities of existing natural drugs, and achieving an overall improvement in efficacy, safety, and practicality.

[0054] Example 1

[0055] S1. Ultrasound extract the Astragalus membranaceus pieces at 60 °C for 40 minutes with an ultrasound power of 300 W. Centrifuge and take the supernatant, concentrate the supernatant to 1 g / mL, add three times the volume of 95% ethanol for vacuum drying, and then purify through a DEAE-cellulose column to obtain the Astragalus polysaccharide extract.

[0056] S2. Dissolve ginsenoside Rg3 and distearoyl phosphatidylcholine in a chloroform-methanol mixed solvent with a volume ratio of 2:1 according to a mass ratio of 1:5. Rotate and evaporate to dryness in a 40 °C water bath until a lipid-like film is formed. Subsequently, blow dry the participating solvent with nitrogen for 30 minutes, then add a phosphate buffer solution with a pH of 7.4 containing 0.9% sodium chloride, and perform ultrasonic treatment at a power of 200 W in a 37 °C water bath. Pause for 15 seconds every 30 seconds of treatment until the film is completely hydrated to obtain a dispersion. Pass the dispersion through an extruder equipped with a polycarbonate membrane with a pore size of 100 nm and reciprocally extrude 10 times under a pressure of 100 bar, and collect the extruded liquid to obtain a stable ginsenoside Rg3 derivative.

[0057] S3. Dissolve the ethanol extract of Ganoderma lucidum spores in a methanol-water mixed solvent with a volume ratio of 4:1, separate by high performance liquid chromatography (HPLC), collect the elution peak with a retention time of 28 - 30 minutes at a wavelength of 254 nm, and obtain Ganoderma acid G crystals through vacuum concentration and freeze drying. Dissolve the Ganoderma acid G crystals in absolute ethanol, with 5 ml of absolute ethanol required for every 100 mg of Ganoderma acid G crystals, add 0.5% poloxamer 188 to obtain a primary suspension, and add the primary suspension to a high-pressure homogenizer and circulate 5 times under a pressure of 100 MPa and then freeze dry to obtain the Ganoderma acid G nanocrystals.

[0058] S4. Mix ligustilide, Tween 80, and glycerol in a ratio of 1:3:2, and drop them into a phosphate buffer solution with a pH of 6.8, and obtain the Angelica sinensis volatile oil microemulsion after ultrasonic emulsification for 30 minutes.

[0059] S5. Dissolve matrine and polyethylene glycol 6000 in ethanol in a ratio of 1:5, and obtain the matrine solid dispersion after spray drying. The inlet temperature of the spray drying is 180 °C and the flow rate is 5 ml / min.

[0060] S6. Mix carboxymethyl chitosan, vitamin E succinate, and sodium chloride in a mass ratio of 15:4:9 to obtain an auxiliary component.

[0061] S7. Stir 20 parts of the Astragalus polysaccharide extract, 15 parts of the ginsenoside Rg3 derivative, 10 parts of the Ganoderma acid G nanocrystals, 5 parts of the Angelica sinensis volatile oil microemulsion, 5 parts of the matrine solid dispersion, and 10 parts of the auxiliary component at room temperature for 2 hours to obtain the pharmaceutical composition for treating colon cancer.

[0062] Example 2

[0063] S1. The Astragalus membranaceus pieces are ultrasonically extracted at 60 °C for 40 minutes with an ultrasonic power of 300 W. After centrifugation, the supernatant is taken, concentrated to 1 g / mL, added with three volumes of 95% ethanol for vacuum drying, and then purified by a DEAE-cellulose column to obtain the Astragalus polysaccharide extract.

[0064] S2. Ginsenoside Rg3 and distearoyl phosphatidylcholine are co-dissolved in a chloroform-methanol mixed solvent with a volume ratio of 2:1 according to a mass ratio of 1:5. It is rotary evaporated to dryness in a 40 °C water bath until a lipid film is formed. Subsequently, after the solvent is blown dry with nitrogen for 30 minutes, a phosphate buffer solution with a pH of 7.4 containing 0.9% sodium chloride is added, and ultrasonic treatment is carried out at a power of 200 W in a 37 °C water bath. It pauses for 15 seconds every 30 seconds of treatment until the film is completely hydrated to obtain a dispersion. The dispersion is extruded reciprocally 10 times under a pressure of 100 bar through an extruder equipped with a polycarbonate membrane with a pore size of 100 nm, and the extruded liquid is collected to obtain a stable ginsenoside Rg3 derivative.

[0065] S3. The ethanol extract of Ganoderma lucidum spores is dissolved in a methanol-water mixed solvent with a volume ratio of 4:1, separated by high performance liquid chromatography (HPLC), and the elution peak with a retention time of 28 - 30 minutes at a wavelength of 254 nm is collected. After vacuum concentration and freeze drying, Ganoderma acid G crystals are obtained. The Ganoderma acid G crystals are dissolved in absolute ethanol, 5 ml of absolute ethanol is required for every 100 mg of Ganoderma acid G crystals, and 0.5% poloxamer 188 is added to obtain a primary suspension. The primary suspension is added to a high-pressure homogenizer and circulated 5 times under a pressure of 100 MPa, and then freeze dried to obtain the Ganoderma acid G nanocrystals.

[0066] S4. Ligustilide, Tween 80, and glycerol are mixed in a ratio of 1:3:2, and dropped into a phosphate buffer solution with a pH of 6.8, and ultrasonic emulsification is carried out for 30 minutes to obtain the Angelica sinensis volatile oil microemulsion.

[0067] S5. Matrine and polyethylene glycol 6000 are dissolved in ethanol in a ratio of 1:5, and the matrine solid dispersion is obtained after spray drying. The inlet temperature of the spray drying is 180 °C, and the flow rate is 5 ml / min.

[0068] S6. Carboxymethyl chitosan, vitamin E succinate, and sodium chloride are mixed according to a mass ratio of 15:4:9 to obtain an auxiliary component.

[0069] S7. 30 parts of Astragalus polysaccharide extract, 20 parts of ginsenoside Rg3 derivative, 15 parts of Ganoderma acid G nanocrystals, 10 parts of Angelica sinensis volatile oil microemulsion, 8 parts of matrine solid dispersion, and 15 parts of auxiliary component are stirred at room temperature for 2 hours to obtain the drug composition for treating colon cancer.

[0070] Example 3

[0071] S1. Ultrasonically extract the Astragalus membranaceus pieces at 60°C for 40 minutes with an ultrasonic power of 300 W. Centrifuge and take the supernatant, concentrate the supernatant to 1 g / mL, add three times the volume of 95% ethanol for vacuum drying, and then purify through a DEAE-cellulose column to obtain the Astragalus polysaccharide extract.

[0072] S2. Dissolve ginsenoside Rg3 and distearoyl phosphatidylcholine in a chloroform-methanol mixed solvent with a volume ratio of 2:1 according to a mass ratio of 1:5. Rotate and evaporate to dryness in a 40°C water bath until a lipid film is formed. Subsequently, blow dry the participating solvent with nitrogen for 30 minutes, add a phosphate buffer solution with 0.9% sodium chloride and a pH of 7.4, and perform ultrasonic treatment at a power of 200 W in a 37°C water bath. Pause for 15 seconds every 30 seconds of treatment until the film is fully hydrated to obtain a dispersion. Pass the dispersion through an extruder equipped with a polycarbonate membrane with a pore size of 100 nm and reciprocally extrude 10 times under a pressure of 100 bar. Collect the extruded liquid to obtain a stable ginsenoside Rg3 derivative.

[0073] S3. Dissolve the ethanol extract of Ganoderma lucidum spores in a methanol-water mixed solvent with a volume ratio of 4:1, separate by high-performance liquid chromatography (HPLC), collect the elution peak with a retention time of 28 - 30 minutes at a wavelength of 254 nm, and obtain ganoderic acid G crystals through vacuum concentration and freeze-drying. Dissolve the ganoderic acid G crystals in absolute ethanol. Every 100 mg of ganoderic acid G crystals requires 5 ml of absolute ethanol, add 0.5% poloxamer 188 to obtain a primary suspension, and add the primary suspension to a high-pressure homogenizer and circulate 5 times under a pressure of 100 MPa and then freeze-dry to obtain the ganoderic acid G nanocrystals.

[0074] S4. Mix ligustilide, Tween 80, and glycerol in a ratio of 1:3:2, and dropwise add them to a phosphate buffer solution with a pH of 6.8, and obtain the Angelica sinensis volatile oil microemulsion after ultrasonic emulsification for 30 minutes.

[0075] S5. Dissolve matrine and polyethylene glycol 6000 in ethanol in a ratio of 1:5, and obtain the matrine solid dispersion after spray drying. The inlet temperature of the spray drying is 180°C and the flow rate is 5 ml / min.

[0076] S6. Mix carboxymethyl chitosan, vitamin E succinate, and sodium chloride according to a mass ratio of 15:4:9 to obtain the auxiliary component.

[0077] S7. After stirring 40 parts of astragalus polysaccharide extract, 30 parts of ginsenoside Rg3 derivative, 20 parts of ganoderic acid G nanocrystals, 15 parts of angelica volatile oil microemulsion, 10 parts of matrine solid dispersion and 20 parts of auxiliary components at room temperature for 2 hours, the pharmaceutical composition for treating colon cancer is obtained.

[0078] It should be noted that:

[0079] In the specification provided herein, a large number of specific details are set forth. However, it will be understood that the embodiments of the present application may be practiced without these specific details. In some instances, well-known structures and techniques have not been shown in detail so as not to obscure the understanding of this specification.

[0080] Similarly, it should be understood that, in order to streamline the present application and assist in understanding one or more of the various inventive aspects, in the foregoing description of the exemplary embodiments of the present application, the various features of the present application are sometimes grouped together in a single embodiment, figure, or description thereof. However, the disclosed system should not be construed as reflecting the following schematic: that the claimed present application requires more features than are expressly recited in each claim.

[0081] Rather, as reflected in the following claims, the inventive aspects lie in less than all the features of the single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into the detailed description, with each claim standing on its own as a separate embodiment of the present application.

[0082] In addition, those skilled in the art will appreciate that although some of the embodiments described herein include certain features included in other embodiments but not others, the combination of features of different embodiments is meant to be within the scope of the present application and forms different embodiments.

[0083] For example, in the following claims, any one of the claimed embodiments can be used in any combination.

[0084] The above is only a preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present application should be covered by the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A pharmaceutical composition for treating colon cancer, characterized in that: The composition includes the following components in parts by weight: 20-40 parts of astragalus polysaccharide extract, 15-30 parts of ginsenoside Rg3 derivative, 10-20 parts of ganoderic acid G nanocrystals, 5-15 parts of angelica volatile oil microemulsion, 5-10 parts of matrine solid dispersion and 10-20 parts of auxiliary components.

2. The pharmaceutical composition for treating colon cancer according to claim 1, characterized in that: The auxiliary component is prepared by mixing a pH-responsive carrier material, an antioxidant and an osmotic pressure regulator in a mass ratio of 15:4:

9.

3. The pharmaceutical composition for treating colon cancer according to claim 1, characterized in that: The preparation method of the astragalus polysaccharide extract is as follows: ultrasonically extracting the astragalus slices, centrifuging to obtain the supernatant, concentrating the supernatant to 1 g / mL, adding three times the volume of ethanol for drying, and purifying to obtain the astragalus polysaccharide extract.

4. The pharmaceutical composition for treating colon cancer according to claim 1, characterized in that: The preparation method of the ginsenoside Rg3 derivative is as follows: ginsenoside Rg3 and distearoylphosphatidylcholine are dissolved in a chloroform-methanol mixed solvent, evaporated in a water bath until a lipid film is formed, then the residual solvent is blown dry, and a phosphate buffer solution is added for ultrasonic treatment until the film is completely hydrated to obtain a dispersion, and the dispersion is extruded through a polycarbonate membrane to obtain the ginsenoside Rg3 derivative.

5. The pharmaceutical composition for treating colon cancer according to claim 1, characterized in that: The preparation method of the ganoderic acid G nanocrystals is as follows: dissolving the ethanol extract of spore powder of ganoderma lucidum in a methanol-water mixed solvent, separating by high performance liquid chromatography (HPLC), eluting, concentrating and drying in sequence to obtain ganoderic acid G crystals, dissolving the ganoderic acid G crystals in anhydrous ethanol, adding 0.5% of a stabilizer to obtain a primary suspension, subjecting the primary suspension to a high pressure circulation treatment, and then freeze-drying to obtain the ganoderic acid G nanocrystals.

6. The pharmaceutical composition for treating colon cancer according to claim 1, characterized in that: The preparation method of the angelica volatile oil microemulsion is as follows: ligustilide, Tween 80 and glycerol are mixed in a ratio of 1:3:2, and the mixture is added dropwise to a phosphate buffer solution of pH 6.8, and the angelica volatile oil microemulsion is obtained after ultrasonic emulsification.

7. The pharmaceutical composition for treating colon cancer according to claim 1, characterized in that: The preparation method of the matrine solid dispersion is as follows: matrine and polyethylene glycol 6000 are dissolved in ethanol at a ratio of 1:5, and the matrine solid dispersion is obtained after spray drying.

8. A method for preparing the pharmaceutical composition for treating colon cancer according to claims 1-7, comprising the following preparation steps: The astragalus polysaccharide extract, ginsenoside Rg3 derivative, ganoderic acid G nanocrystals, angelica volatile oil microemulsion, matrine solid dispersion and auxiliary components are stirred at room temperature to obtain the pharmaceutical composition for treating colon cancer.

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