An oral traditional Chinese medicine composition for treating multiple myeloma and a preparation method thereof

Abstract

This invention relates to the field of traditional Chinese medicine composition technology, and particularly to an oral traditional Chinese medicine composition for treating multiple myeloma and its preparation method. It comprises the following components in parts by weight: Bupleurum chinense 10-12 parts, Cyperus rotundus 8-10 parts, Curcuma longa 8-10 parts, Oroxylum indicum 5-6 parts, Angelica sinensis 8-10 parts, Paeonia lactiflora 8-10 parts, Atractylodes macrocephala 10-12 parts, Poria cocos 10-12 parts, Codonopsis pilosula 8-10 parts, Glycyrrhiza uralensis (processed) 5-6 parts, Agrimonia pilosa 6-8 parts, Bambusa textilis 8-10 parts, Mentha haplocalyx 4-6 parts, and Zingiber officinale 4-6 parts. The composition provided by this invention not only directly inhibits the growth of myeloma cells, but also comprehensively improves the survival prognosis of model animals by regulating liver and spleen function, improving immune status, and reducing phlegm-heat and blood stasis. It provides a stable, safe, and easily promoted oral traditional Chinese medicine preparation for the clinical treatment of multiple myeloma.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to an oral traditional Chinese medicine composition for treating multiple myeloma and its preparation method. Background Technology

[0002] Multiple myeloma (MM) is a malignant hematologic malignancy originating from plasma cells, characterized by the abnormal clonal proliferation of plasma cells in the bone marrow, often leading to bone destruction, kidney damage, anemia, and immune dysfunction. The disease is prevalent in middle-aged and elderly individuals, and its incidence is increasing annually with the aging population. Currently, first-line clinical treatment mainly relies on chemotherapy drugs (such as bortezomib and lenalidomide), glucocorticoids, and autologous stem cell transplantation. Although these treatments prolong patient survival to some extent, long-term use easily leads to drug resistance and significant side effects, such as peripheral neuropathy, bone marrow suppression, and secondary infections, severely impacting patients' quality of life and treatment adherence.

[0003] Traditional Chinese medicine (TCM) plays an increasingly important role in the comprehensive treatment of malignant tumors, especially in reducing the toxic side effects of chemotherapy, reversing drug resistance, improving immune function, and prolonging survival. In TCM, multiple myeloma falls under the categories of "bone pain," "asthenia," and "abdominal masses," with its pathogenesis often attributed to kidney deficiency and essence depletion, internal accumulation of blood stasis and toxins, and phlegm-dampness obstructing the meridians. Based on the principles of "strengthening the body's resistance and eliminating pathogenic factors," "tonifying the kidney and promoting blood circulation," and "detoxifying and removing blood stasis," clinical reports have shown that TCM decoctions, prepared Chinese medicines, or integrated TCM and Western medicine treatments have achieved certain therapeutic effects. However, most existing TCM preparations are used in the form of traditional decoctions or simple extracts, which have drawbacks such as large dosages, unclear active ingredients, and difficulties in quality control.

[0004] The development of oral traditional Chinese medicine (TCM) compound preparations for multiple myeloma is still in its early stages. While some TCM formulations are disclosed in existing patents and literature, most formulas involve numerous ingredients, unclear relationships between the principal, assistant, and adjuvant herbs, and lack systematic integration with modern pharmacology and pharmaceutical processes. In particular, there is a lack of prescriptions specifically designed to target the disease's specific pathological processes (such as bone marrow microenvironment regulation, osteoclast activation inhibition, and myeloma cell cycle arrest). Furthermore, existing formulations are mostly in the form of decoctions or capsules, which suffer from low bioavailability, slow onset of action, and poor patient compliance with long-term use, making it difficult to meet the clinical needs for stable disease control and reduced relapse.

[0005] Therefore, developing a well-formulated, clearly defined, controllable, convenient, and stable oral traditional Chinese medicine composition is of significant practical importance for the clinical treatment of multiple myeloma. This invention, guided by traditional Chinese medicine theory and combined with modern molecular pharmacology and pharmaceutical technology, provides a traditional Chinese medicine composition targeting common syndromes of multiple myeloma (such as kidney deficiency and blood stasis with toxicity). The aim is to synergistically enhance anti-myeloma activity, reduce the toxicity of chemotherapy drugs, and improve bone damage and anemia, thereby improving the overall quality of life and treatment benefits for patients. Summary of the Invention

[0006] The purpose of this invention is to provide an oral traditional Chinese medicine composition for treating multiple myeloma and its preparation method.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides an oral traditional Chinese medicine composition for treating multiple myeloma, comprising the following components in parts by weight: Bupleurum chinense 10-12 parts, Cyperus rotundus 8-10 parts, Curcuma longa 8-10 parts, Oroxylum indicum 5-6 parts, Angelica sinensis 8-10 parts, Paeonia lactiflora 8-10 parts, Atractylodes macrocephala 10-12 parts, Poria cocos 10-12 parts, Codonopsis pilosula 8-10 parts, Glycyrrhiza uralensis (processed) 5-6 parts, Agrimonia pilosa 6-8 parts, Bambusa textilis 8-10 parts, Mentha haplocalyx 4-6 parts, and Zingiber officinale 4-6 parts.

[0008] This invention provides a method for preparing the aforementioned traditional Chinese medicine composition, comprising the following steps: (1) Mix Bupleurum, Cyperus, Curcuma, Oroxylum indicum, Angelica sinensis, Paeonia lactiflora, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, Glycyrrhiza uralensis (processed), Agrimonia pilosa, Bambusa textilis, and fresh ginger with water, soak them, and then decoct for 25-30 minutes. Add mint 5-10 minutes before the end of the decoction and filter out the first decoction. (2) Mix the dregs with water and decoct for 20-25 minutes, then filter the second decoction. (3) Combine the first decoction and the second decoction to obtain the decoction.

[0009] Preferably, the mass ratio of Bupleurum, Cyperus, Curcuma, Oroxylum indicum, Angelica sinensis, Paeonia lactiflora, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, Glycyrrhiza uralensis, Agrimonia pilosa, Bambusa textilis, and Zingiber officinale to water in step (1) is 1:6~9.

[0010] Preferably, the soaking temperature in step (1) is 45~55℃.

[0011] Preferably, the soaking time in step (1) is 4 to 6 hours.

[0012] Preferably, the mass ratio of the dregs to water in step (2) is 1:4~6.

[0013] This invention provides the application of the oral traditional Chinese medicine composition for treating multiple myeloma in the preparation of drugs for treating multiple myeloma.

[0014] Compared with the prior art, the present invention has the following beneficial effects: The formula uses Bupleurum as the chief herb, which is light, clear, and ascending, specifically targeting the liver and gallbladder to relieve stagnant Qi, aligning with the principle of "relieving stagnation of wood." Cyperus rotundus regulates Qi and soothes the liver, Curcuma longa invigorates blood and relieves stagnation, and Oroxylum indicum soothes the liver and harmonizes the stomach. These three herbs regulate Qi without causing dryness, working synergistically with Bupleurum to regulate Qi. Angelica sinensis nourishes and harmonizes blood, and Paeonia lactiflora softens the liver and astringes Yin. These two herbs tonify the liver to assist its function, ensuring that the Qi is released without depleting Yin and blood. These five herbs serve as assistant herbs. Atractylodes macrocephala strengthens the spleen and dries dampness, Poria cocos drains dampness and calms the mind, Codonopsis pilosula is sweet and neutral and tonifies Qi, and Glycyrrhiza uralensis (processed) tonifies and harmonizes the middle Jiao. These four herbs strengthen the spleen to prevent the liver from becoming excessive, reflecting the principle of "when seeing liver disease, knowing that the liver transmits to the spleen, one should first strengthen the spleen." Agrimonia pilosa detoxifies and reduces swelling. When combined with Paeonia lactiflora, it has the effects of synergistically stopping bleeding, softening the liver and relieving pain, and tonifying deficiency and supporting the body's resistance. Bambusa textilis is sweet and cold, clearing away phlegm and calming the mind, preventing Qi stagnation from transforming into fire and generating phlegm. These six herbs serve as adjuvant herbs. Peppermint is pungent and cool, dispersing and penetrating, guiding the medicine to the liver; ginger warms the stomach and harmonizes the middle jiao, and also has medicinal properties. Both are guiding herbs.

[0015] The essence of this formula lies in its combined approach of soothing, nourishing, clearing, and astringing, harmonizing both Qi and blood. Bupleurum, combined with Cyperus, Curcuma, and Oroxylum indicum, amplifies its ability to relieve stagnation without disrupting Qi; Angelica sinensis and Paeonia lactiflora, paired with Agrimonia pilosa, nourish blood and soften the liver, preventing wind-heat from becoming excessive. Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, and Glycyrrhiza uralensis strengthen the spleen and stomach to replenish the body's resources, ensuring the proper functioning of the middle Jiao (spleen and stomach); Bambusa textilis clears the heart and resolves phlegm, preventing stagnant heat from transforming fluids into phlegm and disturbing the mind. Mentha and Zingiber officinale, with their light and penetrating properties, guide the entire formula towards the liver and spleen, ensuring the smooth flow of Qi without stagnation. The combined effects of these herbs soothe the liver, relieve stagnation, strengthen the spleen, nourish blood, protect Yin, and clear phlegm and heat. This formula is suitable for cases of liver stagnation and spleen deficiency with mild phlegm and heat, accompanied by mental depression, poor appetite, and restlessness in the hypochondrium. The formula can be adjusted according to the patient's condition, considering the specific symptoms of cold / heat and deficiency / excess.

[0016] The oral traditional Chinese medicine composition provided by this invention features a refined formulation with clear principal-assistant-adjuvant relationships, a controllable preparation method, sufficient dissolution of active ingredients, and convenient decoction administration. This composition not only directly inhibits the growth of myeloma cells but also comprehensively improves the survival prognosis of model animals by regulating liver and spleen function, improving immune status, and alleviating phlegm-heat and blood stasis. Experiments have verified that all ingredients in the formula are indispensable, ensuring the scientific validity and completeness of the formulation. This provides a stable, safe, and easily applicable oral traditional Chinese medicine preparation for the clinical treatment of multiple myeloma. Detailed Implementation

[0017] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0018] Example 1

[0019] An oral Chinese medicine composition for treating multiple myeloma comprises the following components in parts by weight: Bupleurum chinense 12 parts, Cyperus rotundus 10 parts, Curcuma longa 10 parts, Oroxylum indicum 6 parts, Angelica sinensis 10 parts, Paeonia lactiflora 10 parts, Atractylodes macrocephala 12 parts, Poria cocos 12 parts, Codonopsis pilosula 10 parts, Glycyrrhiza uralensis (processed) 6 parts, Agrimonia pilosa 8 parts, Bambusa textilis 10 parts, Mentha haplocalyx 6 parts, and Zingiber officinale 6 parts.

[0020] Preparation method: (1) Mix Bupleurum, Cyperus, Curcuma, Oroxylum indicum, Angelica sinensis, Paeonia lactiflora, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, Glycyrrhiza uralensis (processed), Agrimonia pilosa, Bambusa textilis, and fresh ginger with water. The total mass of the medicinal materials and the mass ratio of water are 1:9. Soak at 55°C for 6 hours. Then decoct for 30 minutes. Add mint 10 minutes before the end of the decoction. Filter the first decoction.

[0021] (2) Mix the dregs with water at a mass ratio of 1:6, decoct for 25 minutes, and filter out the second decoction.

[0022] (3) Combine the first decoction and the second decoction to obtain the decoction.

[0023] Example 2

[0024] An oral Chinese medicine composition for treating multiple myeloma comprises the following components in parts by weight: Bupleurum chinense 10 parts, Cyperus rotundus 8 parts, Curcuma longa 8 parts, Oroxylum indicum 5 parts, Angelica sinensis 8 parts, Paeonia lactiflora 8 parts, Atractylodes macrocephala 10 parts, Poria cocos 10 parts, Codonopsis pilosula 8 parts, Glycyrrhiza uralensis (processed) 5 parts, Agrimonia pilosa 6 parts, Bambusa textilis 8 parts, Mentha haplocalyx 4 parts, and Zingiber officinale 4 parts.

[0025] Preparation method: (1) Mix Bupleurum, Cyperus, Curcuma, Oroxylum indicum, Angelica sinensis, Paeonia lactiflora, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, Glycyrrhiza uralensis (processed), Agrimonia pilosa, Bambusa textilis, and fresh ginger with water. The total mass of the medicinal materials and the mass ratio of water are 1:6. Soak at 45°C for 4 hours. Then decoct for 25 minutes. Add mint 5 minutes before the end of the decoction. Filter the first decoction.

[0026] (2) Mix the dregs with water at a mass ratio of 1:4, decoct for 20 minutes, and filter out the second decoction.

[0027] (3) Combine the first decoction and the second decoction to obtain the decoction.

[0028] Example 3

[0029] An oral Chinese medicine composition for treating multiple myeloma comprises the following components in parts by weight: Bupleurum chinense 11 parts, Cyperus rotundus 9 parts, Curcuma longa 9 parts, Oroxylum indicum 5.5 parts, Angelica sinensis 9 parts, Paeonia lactiflora 9 parts, Atractylodes macrocephala 11 parts, Poria cocos 11 parts, Codonopsis pilosula 9 parts, Glycyrrhiza uralensis (processed) 5.5 parts, Agrimonia pilosa 7 parts, Bambusa textilis 9 parts, Mentha haplocalyx 5 parts, and Zingiber officinale 5 parts.

[0030] Preparation method: (1) Mix Bupleurum, Cyperus, Curcuma, Oroxylum indicum, Angelica sinensis, Paeonia lactiflora, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, Glycyrrhiza uralensis (processed), Agrimonia pilosa, Bambusa textilis, and fresh ginger with water. The total mass of the medicinal materials and the mass ratio of water are 1:7.5. Soak at 50°C for 5 hours. Then decoct for 28 minutes. Add mint 7.5 minutes before the end of the decoction. Filter the first decoction.

[0031] (2) Mix the dregs with water at a mass ratio of 1:5, decoct for 23 minutes, and filter out the second decoction.

[0032] (3) Combine the first decoction and the second decoction to obtain the decoction.

[0033] Comparative Example 1

[0034] The other methods are the same as in Example 3, except that Agrimonia pilosa is not added.

[0035] Comparative Example 2

[0036] The other methods are the same as in Example 3, except that Bupleurum and Cyperus are not added.

[0037] Comparative Example 3

[0038] The other methods are the same as in Example 3, except that no Tianzhuhuang is added.

[0039] Comparative Example 4

[0040] The other methods are the same as in Example 3, except that no wood butterfly is added.

[0041] Experimental Example 1

[0042] (1) Experimental materials and animal husbandry

[0043] SPF-grade female BALB / c mice, 6-8 weeks old and weighing 18-22 g, were purchased from Wuhan BASF Biotechnology Co., Ltd. After a one-week acclimatization period, the mice were further housed in an SPF-grade laboratory with a relative humidity of 45%-60%, a temperature of 18-20℃, and a 12-hour / 12-hour light / dark cycle, with free access to standard sterilized feed and purified water. Multiple myeloma RPMI8226 cell line was purchased from Shanghai Enzyme Research Institute Co., Ltd., and cultured in RPMI1640 medium (Thermo Fisher Scientific) containing 10% fetal bovine serum, penicillin (100 U / mL), and streptomycin (100 mg / L) in a 37℃, 50% CO2, saturated humidity incubator. After 3-4 passages, cells in the logarithmic growth phase were harvested, and cell density was adjusted with RPMI1640 medium. Trypan blue staining confirmed a viability of >95%.

[0044] (2) Model establishment, grouping and administration

[0045] Healthy BALB / c mice were subcutaneously inoculated with RPMI8226 cells (6 × 10⁻⁶). 5 A multiple myeloma model was established using 1 mouse per group. After inoculation, the mental state, appetite, and activity level of mice in each group were observed daily, and body weight and tumor volume were recorded weekly. The longest diameter (a) and shortest vertical diameter (b) of the tumor were measured using calipers, and the tumor volume (mm³) was calculated using the formula a × b² / 2. When the tumor volume reached 100–120 mm³, the mice were randomly divided into 8 groups of 6 mice each, and administered the decoctions prepared according to the methods in Examples 1–3 and Comparative Examples 1–4 by gavage. The dosage for each group was 0.2 mL / 10 g, administered every other day for a total of 15 doses.

[0046] (3) Observation indicators

[0047] 1. Mouse survival time: Record the number of days from tumor cell inoculation to death for each mouse.

[0048] 2. Tumor inhibition rate: The tumor volume of mice in each group was measured 24 h after the last administration, and the tumor inhibition rate was calculated according to the formula: Tumor inhibition rate (%) = [1 - (tumor volume after administration - tumor volume before administration) / tumor volume before administration] × 100%, and the results are expressed as average values.

[0049] Table 1. Mice survival time

[0050] Table 2 Tumor Inhibition Rate

[0051] Analysis of the results in Tables 1 and 2 leads to the following conclusions: In terms of survival time, the traditional Chinese medicine compositions prepared in Examples 1-3 of this invention can significantly prolong the survival of mice with multiple myeloma, with Example 3 showing particularly outstanding results. In contrast, the survival time of mice in each comparative group was significantly shortened, indicating that the above-mentioned components have an indispensable synergistic effect in prolonging survival in the overall formula. In particular, the absence of Bupleurum and Cyperus rotundus in the formula led to the most significant decrease in survival time, highlighting the core position of the principal herbs in supporting the body's resistance, eliminating pathogenic factors, and regulating Qi.

[0052] Regarding tumor inhibition rate, Examples 1-3 all exhibited high tumor inhibition effects, and the tumor inhibition effects were stable among the examples, indicating that the composition of the present invention has good anti-myeloma activity under the optimized ratio and preparation process. The tumor inhibition rates of the comparative groups were significantly lower than those of the example groups, with Comparative Example 2, lacking Bupleurum and Cyperus, showing the largest decrease in tumor inhibition rate, further verifying the key role of liver-soothing and mood-regulating drugs in inhibiting myeloma growth. Simultaneously, the absence of Agrimonia pilosa, Bambusa textilis, or Oroxylum indicum also weakened the tumor inhibition effect to varying degrees, reflecting the rationality of the formula's multi-target synergistic anti-tumor combination of "soothing, nourishing, clearing, and astringing."

[0053] The combined results of these two indicators demonstrate that the oral traditional Chinese medicine composition of this invention, through the organic combination of principal, assistant, and adjuvant herbs, can effectively improve the survival prognosis and inhibit tumor growth in mice with multiple myeloma. The synergistic effects of each herb, with the absence or reduction of any herb significantly reducing efficacy, prove the scientific validity and completeness of the formulation design. Example 3 showed the best performance in both survival time and tumor inhibition rate, and its preparation parameters can serve as a reference for optimal process selection.

[0054] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. An oral traditional Chinese medicine composition for treating multiple myeloma, characterized in that, The formula includes the following components in parts by weight: Bupleurum chinense 10-12 parts, Cyperus rotundus 8-10 parts, Curcuma longa 8-10 parts, Oroxylum indicum 5-6 parts, Angelica sinensis 8-10 parts, Paeonia lactiflora 8-10 parts, Atractylodes macrocephala 10-12 parts, Poria cocos 10-12 parts, Codonopsis pilosula 8-10 parts, Glycyrrhiza uralensis (processed) 5-6 parts, Agrimonia pilosa 6-8 parts, Bambusa textilis 8-10 parts, Mentha haplocalyx 4-6 parts, and Zingiber officinale 4-6 parts.

2. The preparation method of the traditional Chinese medicine composition according to claim 1, characterized in that, Includes the following steps: (1) Mix Bupleurum, Cyperus, Curcuma, Oroxylum indicum, Angelica sinensis, Paeonia lactiflora, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, Glycyrrhiza uralensis (processed), Agrimonia pilosa, Bambusa textilis, and fresh ginger with water, soak them, and then decoct for 25-30 minutes. Add mint 5-10 minutes before the end of the decoction and filter out the first decoction. (2) Mix the dregs with water and decoct for 20-25 minutes, then filter the second decoction. (3) Combine the first decoction and the second decoction to obtain the decoction.

3. The production method according to claim 2, characterized by, The mass ratio of Bupleurum, Cyperus, Curcuma, Oroxylum indicum, Angelica sinensis, Paeonia lactiflora, Atractylodes macrocephala, Poria cocos, Codonopsis pilosula, Glycyrrhiza uralensis (processed), Agrimonia pilosa, Bambusa textilis, and Zingiber officinale to water in step (1) is 1:6~9.

4. The preparation method according to claim 2, characterized in that, The soaking temperature in step (1) is 45~55℃.

5. The preparation method according to claim 2, characterized in that, The soaking time in step (1) is 4 to 6 hours.

6. The preparation method according to claim 2, characterized in that, The mass ratio of the dregs to water in step (2) is 1:4~6.

7. The use of the oral traditional Chinese medicine composition for treating multiple myeloma as described in claim 1 in the preparation of a drug for treating multiple myeloma.

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