Application of pancreatin combined lucid ganoderma in preparation of medicine for treating leucopenia

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of pancreatin combined lucid ganoderma to preparation of a medicine for treating leucopenia. Research finds that when the lucid ganoderma is independently used, the treatment effect on leucopenia is poor. Compared with the prior art, the pancreatin combined lucid ganoderma can significantly increase the number of leukocytes, the increase amount is higher than the sum of the increase amounts of the pancreatin and the lucid ganoderma when the pancreatin and the lucid ganoderma are independently used, it is indicated that the pancreatin combined lucid ganoderma can be used for treating the leucopenia, the combination of the pancreatin and the lucid ganoderma has a synergistic effect, and more choices are provided for clinical treatment of the leucopenia.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to use of pancreatic enzyme combined with ganoderma lucidum in preparing a medicine for treating leukopenia. Background Art

[0002] White blood cells are an important part of the immune system, responsible for resisting pathogens and monitoring the occurrence of tumors. Leukopenia is one of the common adverse reactions in tumor radiotherapy and chemotherapy. Its main pathogenesis is due to the lack of specificity of anti-tumor drugs. While killing tumor cells, they also cause serious damage to normal cells, especially the rapidly proliferating bone marrow hematopoietic cells, leading to a decrease in white blood cells or even a decrease in all blood cells. The symptoms of leukopenia are mostly manifested as decreased immunity and susceptibility to infection, which not only hinders the progress of tumor treatment, but also seriously affects the patient's quality of life. Therefore, preventing leukopenia is crucial during tumor radiotherapy and chemotherapy.

[0003] Leukopenia refers to a condition in which the white blood cell count in the blood is lower than the normal range. The normal white blood cell count for adults is usually 4-10×10 9 / L. At present, leukopenia is mainly treated with drugs that promote leukopoiesis, such as granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, etc. In addition, some new white blood cell-raising preparations such as immunomodulators are gradually gaining attention. For example, Tremella polysaccharide, as a representative of white blood cell-raising immunomodulators in fungal polysaccharide BRM (MYCO-BRM), has been used in the clinic as an adjuvant treatment for leukopenia caused by tumor radiotherapy and chemotherapy.

[0004] As a traditional medicinal fungus, Ganoderma has been widely studied for its potential use in immune regulation, especially in increasing the number of white blood cells. Since 2010, Ganoderma polysaccharide tablets have been approved by the State Food and Drug Administration for use as an adjuvant treatment for hematopoietic system damage and leukopenia. The research results of Zhang Jianying and other scholars also show that Ganoderma has a significant effect in preventing leukopenia caused by radiotherapy and chemotherapy.

[0005] However, when Lingzhi is used to treat leukocytopenia, its specific effect varies due to individual differences and compatibility methods. For example, the combination of the chemotherapy sensitizer Astragalus and Lingzhi can significantly improve the white blood cell-raising effect. Therefore, studying different types of Lingzhi and their compatibility methods is of great significance for the clinical application of Lingzhi in treating leukocytopenia.

[0006] Pancreatic enzyme is a digestive aid. It is a mixture of various enzymes extracted from the pancreas of animals (such as pigs, sheep or cows). The main ingredients include trypsin, pancreatic amylase and pancreatic lipase.

[0007] At present, there are no other reports on the combination of different types of Ganoderma lucidum and pancreatic enzymes for the treatment of leukocytopenia. Summary of the invention

[0008] In view of the problems of the prior art, the present invention provides a use of pancreatic enzyme combined with Ganoderma lucidum in preparing a medicine for treating leukocytopenia, wherein the Ganoderma lucidum is selected from Ganoderma lucidum No. 1.

[0009] Preferably, the ganoderma lucidum is a crude drug or an extract thereof, and the extract is prepared by: decocting with 2-20 times the volume of water for 1-4 times, each time for 0.5-2 h, combining the filtrate, and concentrating to 0.05-4 g crude drug / mL; Preferably, the dosage of the ganoderma lucidum is 0.5-12 g crude drug / kg, and the dosage of the pancreatic enzyme is 5-100 mg / kg.

[0010] Preferably, the leukopenia is induced by chemotherapy.

[0011] The present invention provides a combined medicine for treating leukocytopenia. The combined medicine is pancreatic enzyme and ganoderma lucidum administered separately or simultaneously. The ganoderma lucidum is selected from the medicine ganoderma lucidum No. 1.

[0012] Preferably, the ganoderma lucidum is a crude drug or an extract thereof, and the extract is prepared by: decocting with 2-20 times the volume of water for 1-4 times, each time for 0.5-2h, combining the filtrate, and concentrating to 0.05-4 g crude drug / mL; Preferably, the dosage of the ganoderma lucidum is 0.5-12 g crude drug / kg, and the dosage of the pancreatic enzyme is 5-100 mg / kg.

[0013] Preferably, the combination drug is used to treat leukopenia.

[0014] Preferably, the leukopenia is induced by chemotherapy.

[0015] The present invention also provides a pharmaceutical composition, which is prepared by using pancreatic enzyme and ganoderma lucidum as active ingredients and adding pharmaceutically acceptable adjuvants or auxiliary ingredients, wherein the ganoderma lucidum is selected from medicinal ganoderma lucidum No. 1.

[0016] Preferably, the weight ratio of Ganoderma lucidum to pancreatic enzyme is 5:1-2400:1.

[0017] The present invention has found through research that when Ganoderma lucidum is used alone, the therapeutic effect on leukocytopenia is poor. In contrast, pancreatic enzyme combined with Ganoderma lucidum can significantly increase the number of white blood cells, and the increase is higher than the sum of the increase when the two are used alone, indicating that pancreatic enzyme combined with Ganoderma lucidum can be used to treat leukocytopenia, and pancreatic enzyme and Ganoderma lucidum have a synergistic effect, which provides more options for the clinical treatment of leukocytopenia.

[0018] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0019] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. DETAILED DESCRIPTION

[0020] In the following examples and experimental examples, reagents and raw materials not specifically described are all commercially available products.

[0021] Example 1 Combination of pancreatic enzyme and ganoderma lucidum for increasing white blood cells This embodiment provides a combined drug of pancreatic enzyme and Ganoderma lucidum, which can be used simultaneously or separately, and the mass ratio of Ganoderma lucidum to pancreatic enzyme is 80:1.

[0022] As a preferred solution, the combined drug is an aqueous solution containing 0.2 g of Ganoderma Lucidum No. 1 / mL and 2.5 mg / mL of pancreatic enzyme.

[0023] Example 2 Combination of pancreatic enzyme and ganoderma lucidum for increasing white blood cells The method is the same as that in Example 1, except that the mass ratio of Ganoderma lucidum and pancreatic enzyme is 5:1. In a preferred embodiment, the combined drug is 0.05 g of Ganoderma lucidum No. 1 / mL aqueous solution and 10 mg / mL pancreatic enzyme solution, which are used independently.

[0024] Example 3 Combination of pancreatic enzyme and ganoderma lucidum for increasing white blood cell count The method is the same as that in Example 1, except that the mass ratio of Ganoderma lucidum to pancreatic enzyme is 2400:1. In a preferred embodiment, the combined drug is an aqueous solution containing 1.2 g of Ganoderma lucidum No. 1 / mL and 0.5 mg / mL of pancreatic enzyme.

[0025] The technical solution of the present invention is further illustrated by experiments below.

[0026] Experimental Example 1 Effect of pancreatic enzyme combined with Ganoderma lucidum on increasing white blood cell count in leukopenic mice 1. Experimental Methods 1. Experimental reagents and drugs: Cyclophosphamide was purchased from Baxter Oncology Gmbh with the national medicine approval number HJ20160467.

[0027] Pancreatic enzyme: derived from porcine pancreas, provided by DeBoer.

[0028] Medicinal Ganoderma Lucidum No. 1 is a variety approved by Sichuan Province (approval number: Sichuan Pharmaceutical 2009005), and the fruiting body is obtained through cultivation.

[0029] ZL214, Ganoderma lucidum, is derived from the patent with publication number CN 116491647 A. The fruiting body obtained by cultivation.

[0030] ZL18, Ganoderma lucidum, is derived from the patent with publication number CN 116200278 A. The fruiting body obtained by cultivation.

[0031] ZL76, Ganoderma lucidum, is derived from the patent with publication number CN 116491647 A. The fruiting body obtained by cultivation.

[0032] 2. Preparation of drug solution Pancreatic enzyme solution: Weigh an appropriate amount of pancreatic enzyme, add water to dissolve and make up to volume so that the final concentration of pancreatic enzyme is 2.5 mg / mL.

[0033] Ganoderma lucidum solution: After slicing Ganoderma lucidum, weigh the raw drug of Ganoderma lucidum, decoct it twice with 10 times the volume of water, 1 h each time, filter, combine the filtrate, concentrate to 0.4 g raw drug / mL under normal pressure, and store at -20℃ for later use. Dilute to 0.2 g raw drug / mL with distilled water before use.

[0034] Pancreatic enzyme combined with Ganoderma lucidum: Weigh an appropriate amount of pancreatic enzyme, add 0.2 g crude drug / ml Ganoderma lucidum solution to dissolve and make up to volume, so that the final concentration of pancreatic enzyme is 2.5 mg / mL.

[0035] 3. Experimental animals KM mice, 110, half male and half female, weighing 18-22 g, were purchased from Sibeifu (Beijing) Biotechnology Co., Ltd., Animal Production License No.: SCXK (Beijing) 2019-0010. KM mice were raised in the SPF Animal Laboratory of the Animal Experiment Center of Sichuan Academy of Traditional Chinese Medicine, Animal Use License No.: SYXK (Sichuan) 2023-0100.

[0036] 4. Animal modeling and drug administration Table 1 After 3 days of adaptive feeding, the mice were randomly divided into 11 groups according to their body weight, as shown in Table 1, namely, normal group, model group, Ganoderma lucidum ZL214 group, Ganoderma lucidum No. 1 group, Ganoderma lucidum ZL18 group, Ganoderma lucidum ZL76 group, pancreatic enzyme group, pancreatic enzyme + Ganoderma lucidum ZL214 group, pancreatic enzyme + Ganoderma lucidum No. 1 group, pancreatic enzyme + Ganoderma lucidum ZL18 group and pancreatic enzyme + Ganoderma lucidum ZL76 group, with 10 mice in each group. On the 4th, 5th and 6th days of the experiment, except for the mice in the normal group, the other mice were intraperitoneally injected with 3 mg / mL cyclophosphamide solution for 3 consecutive days, at a dose of 0.1 mL / 10g body weight. From the 1st to 7th days of the experiment, the other experimental groups except the normal group and the model group were gavaged with the corresponding drugs at a dose of 0.1 mL / 10g body weight, and the normal group and the model group were given an equal volume of distilled water. On the 8th day of the experiment, blood was collected from the canthal venous plexus of each mouse, and the number of white blood cells was determined using a hematology analyzer.

[0037] 2. Experimental Results Table 2 Note: Compared with the normal group, △ indicates P < 0.05, △△ Indicates P<0.01; compared with the model group, * indicates P<0.05, ** indicates P<0.01 As shown in Table 2. Compared with the model group, the number of white blood cells in the Ganoderma lucidum No. 1 group increased by about 0.5×10 9 / L, the increase effect was better, Lingzhi ZL214 group and Lingzhi ZL76 group also had a good effect of increasing white blood cells, while Lingzhi ZL18 group had a weaker effect of increasing white blood cells. The above results show that different types of Lingzhi have differences in increasing white blood cells, but the effect is not significant.

[0038] The number of white blood cells in the mice in the pancreatin group increased by 0.3×10 9 / L, the white blood cell count was better. When pancreatic enzymes were used in combination with Ganoderma lucidum, the white blood cell count of mice was not simply a superposition effect. The white blood cell count of mice in the pancreatic enzyme combined with Ganoderma lucidum No. 1 group increased significantly, reaching 1.4×10 9 / L, which is not only higher than the pancreatic enzyme group and the Ganoderma lucidum No. 1 group, but also higher than the sum of the two. The above results show that the combined use of pancreatic enzyme and Ganoderma lucidum No. 1 has a synergistic effect of increasing white blood cells.

[0039] In summary, through the research of experimental examples, it can be known that pancreatic enzyme combined with Ganoderma lucidum No. 1 can significantly improve the leukopenia caused by chemotherapy drugs. Pancreatic enzyme combined with Ganoderma lucidum can be used to treat leukopenia, which provides more options for the clinical treatment of leukopenia and has good application prospects.

Claims

1. Use of pancreatic enzyme combined with Ganoderma lucidum in the preparation of a drug for treating leukopenia, characterized in that: The ganoderma lucidum is selected from the medicinal ganoderma lucidum No.

1.

2. The use according to claim 1, characterized in that: The ganoderma lucidum is a crude drug or an extract thereof, and the extract is prepared by: decocting with 2-20 times the volume of water for 1-4 times, each time for 0.5-2 hours, combining the filtrate, and concentrating to 0.05-4 g crude drug / mL; And / or, the dosage of the ganoderma lucidum is 0.5-12 g crude drug / kg, and the dosage of the pancreatic enzyme is 5-100 mg / kg.

3. The use according to claim 1, characterized in that: The leukopenia is caused by chemotherapy.

4. A combined drug for treating leukopenia, characterized in that: The combined drug is pancreatic enzyme and ganoderma lucidum administered separately or simultaneously, and the ganoderma lucidum is selected from the medicinal ganoderma lucidum No.

1.

5. The combined drug according to claim 4, characterized in that: The ganoderma lucidum is a crude drug or an extract thereof, and the extract is prepared by: decocting with 2-20 times the volume of water for 1-4 times, each time for 0.5-2 hours, combining the filtrate, and concentrating to 0.05-4 g crude drug / mL; And / or, the dosage of the ganoderma lucidum is 0.5-12 g crude drug / kg, and the dosage of the pancreatic enzyme is 5-100 mg / kg.

6. The combined drug according to claim 4, characterized in that: The combined drug is used for treating leukopenia.

7. The combined drug according to claim 6, characterized in that: The leukopenia is caused by chemotherapy.

8. A pharmaceutical composition, characterized in that: The invention is prepared by taking pancreatic enzyme and ganoderma lucidum as active ingredients, and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients. The ganoderma lucidum is selected from medicinal ganoderma lucidum No.

1.

9. The pharmaceutical composition according to claim 8, characterized in that: The weight ratio of the ganoderma lucidum to pancreatic enzyme is 5:1-2400:1.

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