A traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy.

Abstract

A traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy is prepared from the following medicinal materials in the indicated weight ratios: 6-150 parts Astragalus membranaceus, 2-50 parts Angelica sinensis, 2-50 parts Eclipta prostrata, 2-50 parts Ligustrum lucidum, 2-50 parts Psoralea corylifolia, and 2-30 parts Cuscuta chinensis. This composition can exert effects on hematopoietic function through multiple components and pathways, effectively improving bone marrow suppression caused by chemotherapy. It can be used to synergistically with chemotherapy, improve chemotherapy completion rate, and enhance quality of life during chemotherapy, with significant effects.

Description

[0001] This application is a divisional application of the invention patent application filed on March 27, 2019, with application number 2019102368542 and invention title "Traditional Chinese Medicine Composition for Treating Myelosuppression During Chemotherapy". Technical Field

[0002] This invention belongs to the technical field of traditional Chinese medicine compositions, specifically relating to a traditional Chinese medicine composition for treating bone marrow suppression caused by chemotherapy for malignant tumors and its preparation method. Background Technology

[0003] According to the latest epidemiological survey results, in 2014, the incidence of colorectal cancer in my country ranked third among malignant tumors, after lung cancer and stomach cancer, and its mortality rate ranked fifth among malignant tumors. Chemotherapy is crucial in the treatment of colorectal cancer. However, the adverse reactions of chemotherapy limit the tolerance and adherence of colorectal cancer patients, preventing some patients from benefiting from chemotherapy. Recent research data shows that for stage II / III colon cancer patients, the completion rate of 6 months of standard chemotherapy is only 64%.

[0004] Western medicine's measures for preventing and treating adverse reactions to chemotherapy have limited effectiveness. In my country, traditional Chinese medicine (TCM) is widely used and has proven effective in preventing and treating adverse reactions caused by chemotherapy for tumors. However, due to the diverse schools of thought within TCM, the principles, methods, prescriptions, and medicines for treating malignant tumors vary greatly, and the composition of prescriptions is complex. Furthermore, the complex pharmacological components of Chinese herbs often lead to skepticism from Western medicine regarding their impact on the metabolism and safety of chemotherapy drugs, hindering the use and promotion of TCM in synergistic chemotherapy for tumors.

[0005] Therefore, developing new traditional Chinese medicines that are simple in composition, safe, effective, and easy to use in clinical practice is of great practical significance. Summary of the Invention

[0006] This invention aims to provide a traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy. The composition has relatively simple, safe, and effective medicinal components and is easy to promote. The composition is prepared from the following medicinal materials in the indicated weight ratios: 6-150 parts Astragalus membranaceus, 2-50 parts Angelica sinensis, 2-50 parts Eclipta prostrata, 2-50 parts Ligustrum lucidum, 2-50 parts Psoralea corylifolia, and 2-30 parts Cuscuta chinensis.

[0007] Preferably, the traditional Chinese medicine composition is prepared from the following medicinal materials in the indicated weight ratios: 15-60 parts of raw Astragalus membranaceus, 5-20 parts of Angelica sinensis, 5-20 parts of Eclipta prostrata, 5-20 parts of Ligustrum lucidum, 5-20 parts of Psoralea corylifolia, and 5-20 parts of Cuscuta chinensis.

[0008] Preferably, the traditional Chinese medicine composition is prepared from the following medicinal materials in the indicated weight ratios: 30 parts raw Astragalus membranaceus, 10 parts Angelica sinensis, 10 parts Eclipta prostrata, 10 parts Ligustrum lucidum, 10 parts Psoralea corylifolia, and 10 parts Cuscuta chinensis.

[0009] Preferably, the traditional Chinese medicine composition is a decoction, granules, oral liquid, capsules, or pills.

[0010] Preferably, the decoction of the traditional Chinese medicine composition is prepared by the following method: (I) weigh each traditional Chinese medicine material according to the weight ratio, place all the materials in cold water so that the cold water covers the materials by 2-3 cm, and soak for 1 hour; (II) bring to a boil over high heat, then simmer over low heat for 30 minutes, and take the decoction; (III) add water to the dregs in step (II) so that the water covers the dregs by 2-3 cm, bring to a boil over high heat, then simmer over low heat for 20 minutes, remove the dregs, and take the decoction; and (IV) combine the decoction obtained in step (II) and the decoction obtained in step (III) to obtain the decoction of the traditional Chinese medicine composition.

[0011] Preferably, the granules of the traditional Chinese medicine composition are prepared by the following method: (1) preparing granules of each of the traditional Chinese medicine materials; and (2) mixing the above six granules in corresponding weight parts to obtain the granules of the traditional Chinese medicine composition.

[0012] The granules of each Chinese medicinal herb are prepared according to the following processes.

[0013] Raw Astragalus: Using raw Astragalus slices as raw material, the volatile oil is first extracted, and then 5-10 times the weight of the medicinal material is added to the residue. After two water extractions, the water extracts are combined, concentrated under reduced pressure, and spray-dried to obtain raw Astragalus granules. Each gram of raw Astragalus granules is equivalent to 3-5 grams of raw herb.

[0014] Angelica sinensis: Using Angelica sinensis slices as raw material, the volatile oil is first extracted, and then 5-10 times the weight of the medicinal material is added to the residue. After two water extractions, the water extracts are combined, concentrated under reduced pressure, and spray-dried to obtain Angelica sinensis granules. Each gram of Angelica sinensis granules is equivalent to 3-5 grams of raw herb.

[0015] Eclipta prostrata: Using Eclipta prostrata slices as raw material, soak the raw medicinal material in water for 30-60 minutes, remove the stems, dry and pulverize, add 5-10 times the amount of water, bring to a boil over high heat, then simmer over low heat for 1 hour, take the filtrate, concentrate the filtrate under reduced pressure and dry to obtain Eclipta prostrata granules.

[0016] Privet fruit: Using privet fruit slices as raw material, soak the raw privet fruit in water for 30-60 minutes, remove the stems, dry and crush it, add 5-10 times the weight of the raw material in water, bring to a boil over high heat, then simmer over low heat for 1 hour, take the filtrate, concentrate the filtrate under reduced pressure and dry it to obtain privet fruit granules.

[0017] Psoralea corylifolia: Using Psoralea corylifolia slices as raw material, the raw material is subjected to two consecutive water extractions with 5-10 times the weight of the medicinal material. The filtrates are combined and concentrated under reduced pressure to obtain a concentrated solution. The concentrated solution is dried to obtain a granular intermediate. An appropriate amount of dextrin is mixed into the granular intermediate as an excipient, and the mixture is granulated using a dry granulation machine to obtain a Psoralea corylifolia formulation granule preparation. Each gram of Psoralea corylifolia granule preparation is equivalent to 5-8 grams of raw Psoralea corylifolia.

[0018] Cuscuta: Add 5-10 times the weight of water to the raw Cuscuta medicinal material, enzymatically hydrolyze and extract the Cuscuta medicinal material with cellulase and / or pectinase, filter to obtain filtrate, concentrate the filtrate under reduced pressure to form a clear paste, and dry to obtain Cuscuta granules.

[0019] Based on the chemotherapy drugs, adjuvant chemotherapy drugs, and the patient's physiological characteristics, the main adverse reaction during the second phase of chemotherapy is bone marrow suppression. The kidneys are considered the foundation of innate constitution, governing bone and marrow production, while the spleen is the foundation of acquired constitution, governing digestion and absorption. Therefore, Traditional Chinese Medicine (TCM) treats this by strengthening the spleen and kidneys, and replenishing essence and marrow. Through this theoretical innovation, the aforementioned TCM composition was developed, which effectively improves bone marrow suppression during the second phase of chemotherapy.

[0020] This traditional Chinese medicine composition is simple in structure. Years of clinical practice have shown that when used in conjunction with chemotherapy drugs during treatment, it can increase the completion rate of chemotherapy for colorectal cancer to 78%, thus allowing more patients to benefit from chemotherapy. At the same time, it can significantly improve patients' quality of life during chemotherapy. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail. It should be understood that the specific embodiments described in the specification are merely illustrative and are not intended to limit the scope of protection of this invention.

[0022] Example 1: Formulation of a Traditional Chinese Medicine Composition

[0023] The traditional Chinese medicine composition provided by this invention is prepared from the following medicinal materials in the indicated weight ratios: 6-150 parts of raw Astragalus membranaceus, 2-50 parts of Angelica sinensis, 2-50 parts of Eclipta prostrata, 2-50 parts of Ligustrum lucidum, 2-50 parts of Psoralea corylifolia, and 2-30 parts of Cuscuta chinensis. Preferably, the traditional Chinese medicine composition is prepared from the following medicinal materials in the indicated weight ratios: 15-60 parts of raw Astragalus membranaceus, 5-20 parts of Angelica sinensis, 5-20 parts of Eclipta prostrata, 5-20 parts of Ligustrum lucidum, 5-20 parts of Psoralea corylifolia, and 5-20 parts of Cuscuta chinensis. Most preferably, the traditional Chinese medicine composition is prepared from the following medicinal materials in the indicated weight ratios: 30 parts of raw Astragalus membranaceus, 10 parts of Angelica sinensis, 10 parts of Eclipta prostrata, 10 parts of Ligustrum lucidum, 10 parts of Psoralea corylifolia, and 10 parts of Cuscuta chinensis.

[0024] This traditional Chinese medicine composition is a clinically experienced formula, modified from Dang Gui Bu Xue Tang and Er Zhi Wan based on years of clinical practice. It is suitable for treating and / or alleviating bone marrow suppression caused by chemotherapy.

[0025] Dang Gui Bu Xue Tang (Angelica Blood-Nourishing Decoction) originates from Li Dongyuan's *Treatise on Differentiation of Internal and External Injuries*, and is a classic formula in Traditional Chinese Medicine for invigorating Qi and generating blood. Studies have shown that Astragalus primarily promotes the proliferation of erythroid progenitor cells, while Angelica primarily promotes the proliferation of granulocyte and macrophage progenitor cells. Animal experiments have demonstrated that Dang Gui Bu Xue Tang enhances hematopoietic capacity in mice through multiple effective components and mechanisms: by regulating the hematopoietic microenvironment and balancing the expression of hematopoietic regulatory factors EPO, TPO, and GM-CSF, it promotes the transition of bone marrow hematopoietic cells from G0 / G1 to G2 / M and S phases; it promotes the expression of the anti-apoptotic gene Bcl-2 and the proliferative gene cmy-cmRNA in bone marrow nucleated cells; and it upregulates the expression of the Notch 1 receptor gene and its ligands Jagged 1 and HES 1 in bone marrow cells, thereby promoting intramedullary cell proliferation and inhibiting apoptosis.

[0026] Erzhi Wan originates from *Yifang Jijie* (Collection of Medical Prescriptions) and is composed of two ingredients: Ligustrum lucidum (privet fruit) and Eclipta prostrata (eclipta prostrata). Ligustrum lucidum is best harvested on the winter solstice, while Eclipta prostrata is best harvested on the summer solstice, hence the name Erzhi Wan (Two Solstice Pill). The kidneys store essence, govern bones and produce marrow, and are a water organ, responsible for storing essence and transforming it into blood (*Lvshantang Leibian*, "Differentiation of Blood"). "Blood belongs to the category of essence" (*Jingyue Quanshu*, "Blood Syndrome"). "The kidneys store essence, and essence is what is formed" (*Zhubing Yuanhou Lun*, "Hypoxia Jingxue Chu Hou"). Since essence and blood share the same origin, tonifying the kidneys is crucial in the treatment of blood deficiency. Animal experiments have shown that Erzhi Wan increases white blood cells, red blood cells, and platelets to varying degrees in mice with blood deficiency, with a particularly significant effect on the recovery of white blood cells and platelets. Ligustrum lucidum can effectively improve leukopenia caused by radiotherapy and chemotherapy.

[0027] The remaining two medicinal ingredients in the herbal composition of this invention are Cuscuta chinensis and Psoralea corylifolia. Studies have shown that Cuscuta chinensis extract can induce colony-stimulating factors, thereby promoting the proliferation and differentiation of hematopoietic stem cells. Simultaneously, Cuscuta chinensis aqueous extract can inhibit the growth of papillary carcinoma in mouse models and inhibit the proliferation and differentiation of human gastric cancer cells cultured in vitro. Psoralea corylifolia aqueous extract can increase white blood cells, red blood cells, and platelets in cyclophosphamide-induced mouse models, with the most significant effect on increasing white blood cells.

[0028] The traditional Chinese medicine composition provided by this invention can be prepared into decoctions, granules, oral liquids, capsules, or pills using suitable processes known in the art. This composition can exert its effects on hematopoietic function through multiple components and pathways, effectively improving bone marrow suppression caused by chemotherapy.

[0029] Example 2: Preparation of a Traditional Chinese Medicine Decoction Based on a Traditional Chinese Medicine Composition

[0030] Select high-quality, authentic medicinal materials and weigh them according to the following weight ratio: 30 parts raw Astragalus membranaceus, 10 parts Angelica sinensis, 10 parts Eclipta prostrata, 10 parts Ligustrum lucidum, 10 parts Psoralea corylifolia, and 10 parts Cuscuta chinensis.

[0031] The decoction of traditional Chinese medicine composition is prepared by the following method.

[0032] First, add cold water to cover the herbs by 2-3 cm and soak for 1 hour. Bring to a boil over high heat, then simmer over low heat for 30 minutes. Remove the liquid. Next, add water to the dregs until they are 2-3 cm above the dregs. Bring to a boil over high heat, then simmer over low heat for 20 minutes. Remove the dregs and collect the liquid. Combine the two liquids to obtain a decoction of the traditional Chinese medicine composition.

[0033] Example 3: Preparation of granules of traditional Chinese medicine composition

[0034] Traditional Chinese medicinal herbs that meet the processing standards are selected as raw materials, and various Chinese medicinal materials are weighed according to the following weight ratio: 30 parts of raw Astragalus membranaceus, 10 parts of Angelica sinensis, 10 parts of Eclipta prostrata, 10 parts of Ligustrum lucidum, 10 parts of Psoralea corylifolia, and 10 parts of Cuscuta chinensis.

[0035] Granule formulations of each medicinal herb can be prepared using any suitable process known to those skilled in the art. As an example, granule formulations of each medicinal herb can be prepared as follows.

[0036] Raw Astragalus: First, extract the volatile oil. Add 5-10 times the weight of the raw herb to the residue and perform two water extractions. Combine the water extracts, concentrate under reduced pressure, and spray dry to obtain its granules. Each gram of Astragalus granules is equivalent to 3-5 grams of raw herb.

[0037] Angelica sinensis: First, extract the volatile oil. Add 5-10 times the weight of the medicinal material to the residue and perform two water extractions. Combine the water extracts, concentrate under reduced pressure, and spray dry to obtain its granules. Each gram of Angelica sinensis granules is equivalent to 3-5 grams of raw herb.

[0038] Eclipta prostrata: Soak the raw medicinal material in water for 30-60 minutes, remove the stems, dry and pulverize it, then add 5-10 times the amount of water, bring to a boil over high heat, then simmer over low heat for 1 hour, collect the filtrate, concentrate the filtrate under reduced pressure and dry it to obtain the granule preparation of Eclipta prostrata.

[0039] Privet fruit: Soak the raw medicinal material in water for 30-60 minutes, remove the stems, dry and pulverize it, then add 5-10 times the amount of water, bring to a boil over high heat, then simmer over low heat for 1 hour, collect the filtrate, concentrate the filtrate under reduced pressure and dry it to obtain granules of privet fruit.

[0040] Psoralea corylifolia: The raw material of Psoralea corylifolia is extracted twice with water at a ratio of 5-10 times. The filtrates are combined and concentrated under reduced pressure to obtain a concentrated solution. The concentrated solution is dried to obtain a granular intermediate. An appropriate amount of dextrin is mixed into the granular intermediate as an excipient, and granulation is performed using a dry granulation machine to obtain a granular preparation of Psoralea corylifolia. Each gram of Psoralea corylifolia granular preparation is equivalent to 5-8 grams of raw herb.

[0041] Cuscuta: Add 5-10 times the weight of water to the cuscuta according to its quality, and perform enzymatic hydrolysis and water extraction with cellulase and / or pectinase. Filter to obtain the filtrate, concentrate the filtrate under reduced pressure to obtain a clear extract, and dry to obtain granules of cuscuta.

[0042] The above six granule preparations are mixed to obtain a granule preparation of the traditional Chinese medicine composition. This granule preparation can be further prepared into capsules.

[0043] Recent research data indicates that the completion rate of standard 6-month chemotherapy for stage II / III colorectal cancer patients is only 64%. Gastrointestinal reactions and bone marrow suppression are the main adverse reactions of chemotherapy. The inventors observed 200 chemotherapy patients in an outpatient setting, and the results showed that using the traditional Chinese medicine composition described in this application during chemotherapy could increase the completion rate of chemotherapy for colorectal cancer to 78%, and for other types of tumors, it increased the completion rate by 15%-20%. Simultaneously, the traditional Chinese medicine composition described in this application significantly improved patients' fatigue and other discomforts during chemotherapy, improving their quality of life during this period.

[0044] The above embodiments are merely descriptions of preferred embodiments of the present invention and are not intended to limit the concept and scope of protection of the present invention. Various modifications and improvements made to the technical solutions of the present invention by those skilled in the art without departing from the design concept of the present invention should fall within the scope of protection of the present invention. The technical content for which protection is sought in this invention has been fully described in the claims.

Claims

1. A traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy for colorectal cancer, characterized in that, The traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in the indicated weight ratios: Raw Astragalus membranaceus 15-60 parts, Angelica sinensis 5-20 parts, Eclipta prostrata 5-20 parts, Ligustrum lucidum 5-20 parts, Psoralea corylifolia 5-20 parts, Cuscuta chinensis 5-20 parts.

2. The traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy for colorectal cancer according to claim 1, characterized in that, The traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in the indicated weight ratios: 30 parts raw Astragalus membranaceus, 10 parts Angelica sinensis, 10 parts Eclipta prostrata, 10 parts Ligustrum lucidum, 10 parts Psoralea corylifolia, and 10 parts Cuscuta chinensis.

3. The traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy for colorectal cancer according to claim 1, characterized in that: The traditional Chinese medicine composition is a decoction, granules, oral liquid, capsule, or pill.

4. The traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy for colorectal cancer according to claim 3, characterized in that, The decoction of the traditional Chinese medicine composition is prepared by the following method: (I) Weigh out each Chinese medicinal herb according to the weight ratio, place all the herbs in cold water so that the cold water covers the herbs by 2-3 cm, and soak for 1 hour; (II) Bring to a boil over high heat, then simmer over low heat for 30 minutes and extract the medicinal liquid; (III) Continue adding water until it covers the dregs from step (II) by 2-3 cm. Bring to a boil over high heat, then reduce to a simmer and cook for 20 minutes. Remove the dregs and collect the liquid. (IV) Combine the medicinal juice obtained in step (II) and the medicinal juice obtained in step (III) to obtain the decoction of the traditional Chinese medicine composition.

5. The traditional Chinese medicine composition for treating bone marrow suppression during chemotherapy for colorectal cancer according to claim 3, characterized in that: The granules of the traditional Chinese medicine composition are prepared by the following method: (1) Granules of each Chinese medicinal herb are prepared according to the following processes, wherein: Raw Astragalus: Using raw Astragalus slices as raw material, the volatile oil is first extracted, and 5-10 times the weight of the medicinal material is added to the residue. After two water extractions, the water extracts are combined, concentrated under reduced pressure, and spray-dried to obtain raw Astragalus granules. Each gram of raw Astragalus granules is equivalent to 3-5 grams of raw herb. Angelica sinensis: Using Angelica sinensis slices as raw material, the volatile oil is first extracted, and 5-10 times the weight of the medicinal material is added to the residue. After two water extractions, the water extracts are combined, concentrated under reduced pressure, and spray-dried to obtain Angelica sinensis granules. Each gram of Angelica sinensis granules is equivalent to 3-5 grams of raw herb. Eclipta prostrata: Using Eclipta prostrata slices as raw material, soak the raw medicinal material of Eclipta prostrata in water for 30-60 minutes, remove the stems, dry and pulverize, add 5-10 times the amount of water of the medicinal material, bring to a boil over high heat, simmer over low heat for 1 hour, take the filtrate, concentrate the filtrate under reduced pressure and dry to obtain Eclipta prostrata granules. Privet fruit: Using privet fruit slices as raw material, soak the raw privet fruit in water for 30-60 minutes, remove the stems, dry and pulverize, add 5-10 times the weight of the raw material in water, bring to a boil over high heat, then simmer over low heat for 1 hour, take the filtrate, concentrate the filtrate under reduced pressure and dry it to obtain privet fruit granules. Psoralea corylifolia: Using Psoralea corylifolia slices as raw material, the raw material is subjected to two consecutive water extractions with 5-10 times the weight of the medicinal material, and the filtrates are combined. The filtrate is concentrated under reduced pressure to obtain a concentrated solution. The concentrated solution is dried to obtain a granule intermediate. An appropriate amount of dextrin is mixed into the granule intermediate as an excipient, and the mixture is granulated by a dry granulation machine to obtain a Psoralea corylifolia formulation granule preparation. Each gram of Psoralea corylifolia granule preparation is equivalent to 5-8 grams of raw Psoralea corylifolia. Cuscuta: Add 5-10 times the weight of water to the raw material of Cuscuta, enzymatically hydrolyze and extract the raw material of Cuscuta with cellulase and / or pectinase, filter to obtain filtrate, concentrate the filtrate under reduced pressure to form a clear paste, and dry to obtain Cuscuta granules. (2) The above six granule preparations are mixed to obtain the granules of the traditional Chinese medicine composition.