Oral liquid for treating weakness after illness and regulating immunity after radiotherapy and chemotherapy and preparation method of oral liquid

Abstract

The invention discloses oral liquid for treating weakness after illness and regulating immunity after radiotherapy and chemotherapy and a preparation method, and relates to the technical field of health care products. The oral liquid comprises the following components: astragalus membranaceus, lucid ganoderma, liquorice, chrysanthemum, coix seeds and oysters. By optimizing a formula and an extraction method, the effect of improving immunity is enhanced, adverse reaction after radiotherapy is relieved, meanwhile, the components are safe and have no adverse effect on the liver, and the storage stability of the active components is higher.

Description

Technical Field

[0001] The invention relates to the technical field of health care products, and in particular to an oral liquid for regulating immunity after illness and chemotherapy and a preparation method thereof. Background Art

[0002] Cytotoxicity is one of the main ways that chemotherapeutic drugs inhibit the rapid growth of malignant tumors. At the same time, chemotherapeutic drugs inhibit the normal growth of bone marrow cells, causing bone marrow suppression. Bone marrow suppression is mainly manifested by leukopenia, anemia, and thrombocytopenia. Therefore, leukopenia can lead to an increased risk of complications of infection and sepsis after chemotherapy, and is one of the important manifestations of chemotherapy-induced immunodeficiency. T lymphocytes are an important component of the body's immune system, and they are involved in important processes such as tumor immune surveillance, cell killing, and immune regulation. Chemotherapy and radiotherapy usually cause a rapid decline in the patient's immunity. Clinically, blood transfusions or cytokine drugs are often used to assist in reducing chemotherapy-induced immunodeficiency, but long-term large-scale blood transfusions pose a risk of infection, and cytokine drugs have a single effect and are expensive.

[0003] Therefore, low immunity caused by radiotherapy and chemotherapy is an urgent problem to be solved in the clinical application of radiotherapy and chemotherapy drugs. At the same time, physical weakness caused by illness is also a manifestation of the failure of immunity to recover in time.

[0004] Wang Bing et al. studied the effect of Junzi Fuzheng Decoction on reducing toxicity, enhancing efficacy and enhancing immunity of patients with colorectal cancer after surgery. They found that after 6 cycles of chemotherapy, the CD3 + , CD4 + , CD8 + The level of leukemia in the patients with colorectal cancer increased significantly, and the difference was statistically significant compared with the chemotherapy group alone (P < 0.05). Therefore, Junzi Fuzheng Decoction combined with chemotherapy drugs can inhibit tumor growth in patients with colorectal cancer, improve the quality of life, reduce the adverse reactions caused by postoperative chemotherapy, and improve the immune function of patients.

[0005] Chinese patent CN101129607A discloses a Chinese medicine oral liquid for treating immune function damage after chemotherapy in patients with esophageal cancer, characterized in that it is composed of the following drug raw materials in weight percentage: 9-11% of ginseng, 18-22% of astragalus, 8-10% of cordyceps, 9-11% of atractylodes, 14-16% of tuckahoe, 8-10% of liquorice, 11-13% of angelica, and 14-16% of wolfberry. The Chinese medicine oral liquid for treating immune function damage after chemotherapy in patients with esophageal cancer shows obvious therapeutic effects in peripheral blood immunoglobulin, serum cytokine interleukin, blood picture, and clinical symptoms, has no toxic side effects, and can reduce the treatment cost of patients.

[0006] At present, there is still a shortage of health care products for treating weakness after illness and regulating immunity after radiotherapy and chemotherapy. Summary of the invention

[0007] In view of this, the purpose of the present invention is to provide an oral liquid and a preparation method for regulating immunity in patients with weakness after illness and after radiotherapy and chemotherapy. By optimizing the formula and extraction method, the effect of improving immunity is enhanced and the adverse reactions after radiotherapy are alleviated. At the same time, the ingredients are safe and have no adverse effects on the liver. At the same time, the storage stability of the active ingredients is higher.

[0008] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0009] In one aspect, the present invention provides an oral liquid for regulating immunity after illness and chemotherapy, comprising the following ingredients: astragalus, ganoderma lucidum, liquorice, chrysanthemum, coix seed and oyster.

[0010] Preferably, the oral liquid comprises the following ingredients in parts by weight: 10-20 parts of astragalus, 10-20 parts of ganoderma lucidum, 10-20 parts of licorice, 7-14 parts of chrysanthemum, 5-10 parts of coix seeds and 5-10 parts of oyster.

[0011] Further preferably, the oral liquid comprises the following ingredients in parts by weight: 15 parts of astragalus, 15 parts of ganoderma lucidum, 15 parts of licorice, 10 parts of chrysanthemum, 5 parts of coix seed and 5 parts of oyster.

[0012] In another aspect, the present invention provides a method for preparing the oral liquid, comprising the following steps:

[0013] (1) adding water to the formulated amount of coix seed and oyster, adjusting the pH to 7.5-10, extracting 2-4 times, and combining to obtain an extract;

[0014] (2) applying the extract obtained in step (1) to a macroporous resin column, and eluting with 20-35% ethanol aqueous solution, 40-50% ethanol aqueous solution, and 75-85% ethanol aqueous solution in sequence, collecting 40-50% of the eluate, drying, and completely removing the solvent to obtain a solid;

[0015] (3) Add the prescribed amount of Astragalus, Ganoderma lucidum, Licorice, and Chrysanthemum to water and boil for 2-4 times, combine the filtrates, and concentrate to a density of 1.02-1.10 g / cm 3 , get the extract;

[0016] (4) Mix the solids, extract and water to adjust the solid content to 5-20%, add crystal sugar, stir and dissolve to obtain the oral solution.

[0017] Preferably, in step (1), the extraction conditions are: adding 5-10 times the total weight of the medicinal materials in water each time, extracting at 50-90°C for 4-6 hours, and more preferably, adding 8 times the total weight of the medicinal materials in water each time, extracting at 75°C for 5 hours.

[0018] Preferably, in step (1), the pH is adjusted to 8.0.

[0019] Preferably, in step (1), the extraction is performed twice.

[0020] Preferably, in step (2), the macroporous resin is selected from AB-8 macroporous resin or DA201-C macroporous resin, and more preferably DA201-C macroporous resin.

[0021] Preferably, step (2) is specifically as follows: subjecting the filtrate obtained in step (1) to a macroporous resin column at a flow rate of 0.5-1.5 BV / h, eluting with 20-35% ethanol aqueous solution, 40-50% ethanol aqueous solution, and 75-85% ethanol aqueous solution in sequence, with the elution volume being 2-4 BV, collecting 40-50% of the eluate, drying, and completely removing the solvent to obtain a solid.

[0022] Preferably, step (2) is specifically as follows: subjecting the filtrate obtained in step (3) to a macroporous resin column at a flow rate of 0.8 BV / h, eluting with 30% ethanol aqueous solution, 45% ethanol aqueous solution, and 82% ethanol aqueous solution in sequence, with the elution volume being 2 BV each, collecting 45% of the eluate, drying, and completely removing the solvent to obtain a solid.

[0023] Preferably, in step (3), the decoction extraction is specifically as follows: first adding water in an amount of 10-20 times the weight of the medicinal material, extracting for 3-5 hours, filtering, adding water in an amount of 5-15 times the weight of the residue again, extracting for 1-3 hours, and combining the filtrate.

[0024] Further preferably, in step (3), the decoction extraction is specifically as follows: adding 15 times the weight of the medicinal material in water for the first time, extracting for 4 hours, filtering, adding 10 times the weight of the residue in water again, extracting for 2 hours, and combining the filtrate.

[0025] Preferably, in step (4), the solid content is 10%.

[0026] Preferably, in step (4), the crystal sugar content is 0.5-5% of the oral liquid, more preferably 3%.

[0027] The beneficial effects of the present invention are:

[0028] (1) The present invention uses astragalus, ganoderma lucidum, liquorice, chrysanthemum, coix seed and oyster in a specific ratio, which has good effects of improving immunity and alleviating adverse reactions after radiotherapy.

[0029] (2) The oral liquid of the present invention is prepared by a specific preparation process, which significantly improves the effect of the oral liquid and improves the stability of the active ingredients, ensuring the quality of the oral liquid is stable under long-term storage, does not add preservatives, and has high safety. The optimized preparation process obtains a product with better immunity-enhancing effect. DETAILED DESCRIPTION

[0030] In order to make the technical means, creative features, purpose and efficacy of the present invention easy to understand, the present invention is further explained in conjunction with specific embodiments below, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without creative work all belong to the protection scope of the present invention. In the following embodiments, unless otherwise specified, the operating methods used are conventional operating methods, the equipment used are conventional equipment, and the equipment materials used in each embodiment are the same.

[0031] Example 1

[0032] Embodiment 1 medicine formula is as follows:

[0033] 15 parts of astragalus, 15 parts of ganoderma lucidum, 15 parts of liquorice, 10 parts of chrysanthemum, 5 parts of coix seeds, and 5 parts of oyster.

[0034] Follow these steps to prepare:

[0035] (1) Add water to the formulated amount of coix seed and oyster, adjust the pH to 8.0, extract twice, add 8 times the total weight of the medicinal materials of water each time, extract at 75°C for 5 hours, and combine the extracts;

[0036] (2) The extract obtained in step (1) was loaded onto a DA201-C macroporous resin column at a flow rate of 0.8 BV / h, and eluted with 30% ethanol aqueous solution, 45% ethanol aqueous solution, and 82% ethanol aqueous solution in sequence, with the elution volume being 2 BV each, and 45% of the eluate was collected and dried to completely remove the solvent to obtain a solid;

[0037] (3) Add water to the formula amount of Astragalus, Ganoderma lucidum, Licorice, and Chrysanthemum and boil them. First, add 15 times the weight of the medicinal materials in water, extract for 4 hours, filter, add 10 times the weight of water to the residue again, extract for 2 hours, combine the filtrate, and concentrate to a density of 1.02-1.10 g / cm 3 , get the extract;

[0038] (4) The solids, extract and water are mixed to adjust the solid content to 10%, and crystal sugar is added to an amount of 3% of the oral solution, and stirred to dissolve to obtain the oral solution.

[0039] Example 2

[0040] Embodiment 2 medicine formula is as follows:

[0041] 10 parts of astragalus, 20 parts of ganoderma lucidum, 20 parts of liquorice, 7 parts of chrysanthemum, 5 parts of coix seeds, and 5 parts of oyster.

[0042] The preparation method is the same as that of Example 1.

[0043] Example 3

[0044] Embodiment 3 medicine prescription is as follows:

[0045] 20 parts of astragalus, 10 parts of ganoderma lucidum, 10 parts of liquorice, 14 parts of chrysanthemum, 10 parts of coix seeds, and 10 parts of oyster.

[0046] The preparation method is the same as that of Example 1.

[0047] Comparative Example 1

[0048] The drug formulation of Comparative Example 1 is as follows:

[0049] 25 parts of astragalus, 20 parts of ganoderma lucidum, 5 parts of liquorice, 5 parts of chrysanthemum, 2 parts of coix seed, and 8 parts of oyster.

[0050] The preparation method is the same as that of Example 1.

[0051] Comparative Example 2

[0052] The drug formulation of Comparative Example 2 is as follows:

[0053] 10 parts of astragalus, 10 parts of ganoderma lucidum, 20 parts of liquorice, 15 parts of chrysanthemum, 9 parts of coix seeds, and 1 part of oyster.

[0054] The preparation method is the same as that of Example 1.

[0055] Example 4

[0056] Embodiment 4 medicine formula is as follows:

[0057] 15 parts of astragalus, 15 parts of ganoderma lucidum, 15 parts of liquorice, 10 parts of chrysanthemum, 5 parts of coix seeds, and 5 parts of oyster.

[0058] Follow these steps to prepare:

[0059] (1) Add water to the formulated amount of coix seed and oyster, adjust the pH to 8.0, extract twice, add 5 times the total weight of the medicinal materials of water each time, extract at 50°C for 6 hours, and combine the extracts;

[0060] (2) The extract obtained in step (1) was loaded onto a DA201-C macroporous resin column at a flow rate of 1.5 BV / h, and eluted with 35% ethanol aqueous solution, 50% ethanol aqueous solution, and 85% ethanol aqueous solution in sequence, with an elution volume of 4 BV each, and 50% of the eluate was collected and dried to completely remove the solvent to obtain a solid;

[0061] (3) Add water to the formula amount of Astragalus, Ganoderma lucidum, Licorice, and Chrysanthemum and boil them. First, add 20 times the weight of the medicinal materials in water, extract for 5 hours, filter, add 5 times the weight of water to the residue again, extract for 1 hour, combine the filtrate, and concentrate to a density of 1.02-1.10 g / cm 3 , get the extract;

[0062] (4) The solids, extract and water are mixed to adjust the solid content to 10%, and crystal sugar is added to an amount of 3% of the oral solution, and stirred to dissolve to obtain the oral solution.

[0063] Example 5

[0064] Embodiment 5 medicine prescription is as follows:

[0065] 15 parts of astragalus, 15 parts of ganoderma lucidum, 15 parts of liquorice, 10 parts of chrysanthemum, 5 parts of coix seeds, and 5 parts of oyster.

[0066] Follow these steps to prepare:

[0067] (1) Add water to the formulated amount of coix seed and oyster, adjust the pH to 8.0, extract twice, add 10 times the total weight of the medicinal materials of water each time, extract at 90°C for 4 hours, and combine the extracts;

[0068] (2) The extract obtained in step (1) was loaded onto a DA201-C macroporous resin column at a flow rate of 0.5 BV / h, and eluted with 20% ethanol aqueous solution, 40% ethanol aqueous solution, and 75% ethanol aqueous solution in sequence, with the elution volume being 2 BV each, and 40% of the eluate was collected and dried to completely remove the solvent to obtain a solid;

[0069] (3) Add water to the formula amount of Astragalus, Ganoderma lucidum, Licorice, and Chrysanthemum and boil them. First, add 10 times the weight of the medicinal materials in water, extract for 3 hours, filter, add 15 times the weight of the residue in water again, extract for 3 hours, combine the filtrate, and concentrate to a density of 1.02-1.10 g / cm 3 , get the extract;

[0070] (4) The solids, extract and water are mixed to adjust the solid content to 10%, and crystal sugar is added to an amount of 3% of the oral solution, and stirred to dissolve to obtain the oral solution.

[0071] Example 6

[0072] The difference from Example 1 is that AB-8 macroporous resin is used in step (2), and the rest is the same.

[0073] Comparative Example 3

[0074] The difference from Example 1 is that in step (2), the eluate of 30% ethanol water is collected to prepare a solid, and the rest is the same.

[0075] Comparative Example 4

[0076] The difference from Example 1 is that in step (2), the eluate of 82% ethanol water is collected to prepare a solid, and the rest is the same.

[0077] Comparative Example 5

[0078] (1) Add water to the formulated amount of coix seed, oyster, astragalus, ganoderma, licorice, and chrysanthemum and boil them. First, add 15 times the weight of the medicinal materials in water, extract for 4 hours, filter, add 10 times the weight of water to the residue again, extract for 2 hours, combine the filtrate, and concentrate to a density of 1.02-1.10 g / cm 3 , get the extract;

[0079] (2) Mix the extract and water, adjust the solid content to 10%, add crystal sugar, the crystal sugar content is 3% of the oral liquid, stir and dissolve, and obtain the oral liquid.

[0080] Comparative Example 6

[0081] (1) Add water to the formulated amount of coix seed, oyster, astragalus, ganoderma, licorice, and chrysanthemum, adjust the pH to 8.0, extract twice, add 8 times the total weight of the medicinal materials of water each time, extract at 75°C for 5 hours, and combine the extracts;

[0082] (2) The extract obtained in step (1) was loaded onto a DA201-C macroporous resin column at a flow rate of 0.8 BV / h, and eluted with 30% ethanol aqueous solution, 45% ethanol aqueous solution, and 82% ethanol aqueous solution in sequence, with the elution volume being 2 BV each, and 45% of the eluate was collected and dried to completely remove the solvent to obtain a solid;

[0083] (3) The solids, extract and water are mixed to adjust the solid content to 10%, and crystal sugar is added to an amount of 3% of the oral solution, and stirred to dissolve to obtain the oral solution.

[0084] Results

[0085] 1. Animal experiments

[0086] 1.1 Lymphocyte transformation rate

[0087] Detection method: Male mice weighing 18-22g were adaptively fed for one week and randomly divided into groups, with 10 mice in each group. The experimental groups were administered with the compositions prepared in Examples 1-6 and Comparative Examples 1-6, respectively, at a dosage of 30mL / kg / day, and the control group was administered with an equal amount of normal saline, and 0.6mL of water was orally administered. On the 1st and 3rd day after administration, each mouse was intramuscularly injected with 6mg / kg of phytohemagglutinin. On the 6th day, blood slides were taken, stained with Wright staining, and examined under a microscope. The results are as follows:

[0088]

[0089]

[0090] In the table, compared with the control group, *P<0.05, **P<0.01.

[0091] The results show that the oral liquid prepared in the embodiment of the present invention can significantly improve the transformation rate of lymphocytes, and the degree of improvement is significantly better than that of the comparative example.

[0092] 1.2 Protective effect on immunosuppressed mice

[0093] Female mice weighing 18-22g were adaptively raised for one week and randomly divided into groups of 10 mice per group. The experimental groups were respectively administered the compositions prepared in Examples 1-6 and Comparative Examples 1-6, with a dosage of 30mL / kg / day, and the control group and the model group were administered with an equal amount of normal saline, and 0.6mL of water was administered orally. Except for the control group, the remaining groups were intraperitoneally injected with cyclophosphamide 40mg / kg for two consecutive days after 3 weeks of administration. After 4 weeks of gavage, the mice were killed by dislocation, the thymus and spleen were removed, the surface dirt was removed with filter paper, weighed, and the thymus index and spleen index were calculated.

[0094]

[0095]

[0096] In the table, compared with the control group, *P<0.05; compared with the model group, #P<0.05.

[0097] The results showed that the oral liquids prepared in Examples 1-6 of the present invention can significantly improve the thymus index and spleen index of immunosuppressed mice.

[0098] 1.3 Protective effect on FLV-infected mice

[0099] Female SPF BALB / C mice weighing 18-22g were adaptively raised for one week and randomly divided into groups, with 10 mice in each group. Except for the control group, the other groups were intraperitoneally injected with FLV (Friend type murine leukemia virus), and the administration began 1 day after the virus injection. Mice infected with FLV will rapidly develop severe immunodeficiency. The experimental groups were respectively administered with the compositions prepared in Examples 1-6 and Comparative Examples 1-6, with a dosage of 30mL / kg / day. The control group and the model group were administered with an equal amount of physiological saline, and 0.6mL of water was orally administered. After 3 weeks of infection, the mice were killed by dislocation, the spleen was aseptically removed, and placed in a small dish containing an appropriate amount of sterile Hanks solution. The spleen was gently shredded with tweezers, filtered through a 200-mesh sieve, and a single cell suspension was prepared for the mouse NK cell activity test.

[0100]

[0101]

[0102] In the table, compared with the control group, *P<0.05, **P<0.01; compared with the model group, #P<0.05, ##P<0.01.

[0103] The results show that both the example and the comparative example can significantly improve the NK cell activity of mice infected with FLV. From the perspective of specific activity values, the example has more advantages.

[0104] 2. Clinical trials

[0105] Observation subjects: patients diagnosed with tumors by histopathology or cytology, receiving radiotherapy 5 times a week, with a primary lesion dose of 800-1000 CGY / week, mainly patients with nasopharyngeal carcinoma, lung cancer, etc.

[0106] Observation method: 60 patients were divided into two groups. The treatment group was given the oral solution prepared in Example 1 and started drinking it two days before the start of radiotherapy, 30 mL × 5 times a day for 4 weeks. The control group was not given any medicine, and the radiotherapy response of the subjects was recorded every week.

[0107] 1. Check and record the total white blood cell count.

[0108] 2. Observe six items: dizziness, nausea, vomiting, dry throat, sore throat and oral mucosal congestion.

[0109] The total white blood cell count results are as follows:

[0110] Group Number of cases Before radiotherapy Radiotherapy for 3 weeks Rate of change Control group 30 6640±1300 5270±1200 20.6％ Treatment Group 30 6760±1400 6520±1600 3.6％

[0111] The results showed that the decrease in the total white blood cell count of the patients who drank the oral solution of Example 1 was significantly reduced.

[0112] The number of cases of radiotherapy reactions is as follows:

[0113]

[0114]

[0115] The results showed that after drinking the oral liquid of Example 1, the number of patients experiencing dizziness, nausea, vomiting, dry throat, sore throat and oral mucosal congestion decreased significantly.

[0116] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. An oral liquid for regulating immunity after illness and chemotherapy, characterized in that: Includes the following ingredients: Astragalus, Ganoderma Lucidum, Licorice, Chrysanthemum, Coix Seed and Oyster.

2. The oral liquid according to claim 1, characterized in that The oral liquid comprises the following ingredients in parts by weight: 10-20 parts of astragalus, 10-20 parts of ganoderma lucidum, 10-20 parts of liquorice, 7-14 parts of chrysanthemum, 5-10 parts of coix seeds and 5-10 parts of oyster.

3. The oral liquid according to claim 2, characterized in that The oral liquid comprises the following ingredients in parts by weight: 15 parts of astragalus, 15 parts of ganoderma lucidum, 15 parts of liquorice, 10 parts of chrysanthemum, 5 parts of coix seeds and 5 parts of oyster.

4. The method for preparing the oral liquid according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) adding water to the formulated amount of coix seed and oyster, adjusting the pH to 7.5-10, extracting 2-4 times, and combining to obtain an extract; (2) applying the extract obtained in step (1) to a macroporous resin column, and eluting with 20-35% ethanol aqueous solution, 40-50% ethanol aqueous solution, and 75-85% ethanol aqueous solution in sequence, collecting 40-50% of the eluate, drying, and completely removing the solvent to obtain a solid; (3) Add the prescribed amount of Astragalus, Ganoderma lucidum, Licorice, and Chrysanthemum to water and boil for 2-4 times, combine the filtrates, and concentrate to a density of 1.02-1.10 g / cm 3 , get the extract; (4) Mix the solid, extract and water to adjust the solid content to 5-20%, add crystal sugar, stir and dissolve to obtain the oral solution.

5. The preparation method according to claim 4, characterized in that: In step (1), the extraction conditions are: adding 5-10 times the total weight of the medicinal materials with water each time, extracting at 50-90° C. for 4-6 hours; the extraction is repeated twice.

6. The preparation method according to claim 4, characterized in that: In step (1), the pH is adjusted to 8.

0.

7. The preparation method according to claim 4, characterized in that: In step (2), the macroporous resin is selected from AB-8 macroporous resin or DA201-C macroporous resin.

8. The preparation method according to claim 7, characterized in that: The macroporous resin is DA201-C macroporous resin.

9. The preparation method according to claim 4, characterized in that: Step (2) is specifically as follows: applying the filtrate obtained in step (1) to a macroporous resin column at a flow rate of 0.5-1.5 BV / h, eluting with 20-35% ethanol aqueous solution, 40-50% ethanol aqueous solution, and 75-85% ethanol aqueous solution in sequence, with the elution volume being 2-4 BV each, collecting 40-50% of the eluate, drying, and completely removing the solvent to obtain a solid; Preferably, step (2) is specifically as follows: subjecting the filtrate obtained in step (3) to a macroporous resin column at a flow rate of 0.8 BV / h, eluting with 30% ethanol aqueous solution, 45% ethanol aqueous solution, and 82% ethanol aqueous solution in sequence, with the elution volume being 2 BV each, collecting 45% of the eluate, drying, and completely removing the solvent to obtain a solid.

10. The preparation method according to claim 4, characterized in that: In step (3), the decoction extraction is specifically as follows: firstly adding water in an amount of 10-20 times the weight of the medicinal material, extracting for 3-5 hours, filtering, adding water in an amount of 5-15 times the weight of the residue again, extracting for 1-3 hours, and combining the filtrate.

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