Pharmaceutical composition for preventing and / or treating leucopenia caused by chemotherapy and preparation method thereof
Through specific formulations and processing of traditional Chinese medicine, the lack of targeted treatment for leukopenia after chemotherapy has been addressed, resulting in improved immune function and white blood cell levels in chemotherapy patients, thus resolving the problem of weakened immunity after chemotherapy.
Patent Information
- Application Number
- CN202511869103.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-11
- Publication Date
- 2026-03-17
AI Technical Summary
Existing Chinese herbal formulas lack specificity in treating chemotherapy-induced leukopenia, resulting in poor efficacy or slow onset of action. Furthermore, unprocessed drugs may affect efficacy or cause adverse reactions.
This treatment uses a combination of traditional Chinese medicines, including red ginseng, prepared rehmannia root, morinda root, tangerine peel, dodder seed, atractylodes rhizome, yam, astragalus root, poria cocos, achyranthes root, cistanche, cinnamon, angelica root, wolfberry fruit, deer antler, fennel, and licorice root, which are processed in a specific way to create a synergistic effect and enhance the efficacy of tonifying the liver and kidneys. It is used in conjunction with the chemotherapy drug 5-fluorouracil to promote the proliferation of lymphocytes and monocytes.
It effectively prevents and treats chemotherapy-induced leukopenia, enhances the immune function of chemotherapy patients, increases white blood cell levels by promoting the proliferation of lymphocytes and monocytes, and reduces the side effects of chemotherapy.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of technology, and more particularly to a pharmaceutical composition for the prevention and / or treatment of chemotherapy-induced leukopenia and a method for its preparation. Background Technology
[0002] Leukopenia is a common side effect of chemotherapy for cancer, which reduces the patient's ability to fight infection. In severe cases, it can lead to the termination of chemotherapy and affect the treatment effect.
[0003] In the field of traditional Chinese medicine, the treatment concept of "strengthening the body's resistance and eliminating pathogenic factors" has always been emphasized. In the treatment of tumors, the use of traditional Chinese medicine to "strengthen the body's resistance" in order to reduce the toxic side effects of chemotherapy has become an important adjunctive treatment method. Summary of the Invention
[0004] Research has revealed several traditional Chinese medicine formulas for increasing white blood cell counts in existing technologies. These formulas primarily focus on tonifying qi and blood, and nourishing the liver and kidneys. However, they often lack specificity for the complex pathogenesis of "qi and blood deficiency, spleen and kidney weakness, and stagnation of cold pathogens" caused by the potent and toxic effects of chemotherapy drugs, resulting in poor clinical efficacy or slow onset of action.
[0005] However, this invention has found that a traditional Chinese medicine composition composed of red ginseng, prepared rehmannia root, morinda root, tangerine peel, dodder seed, atractylodes rhizome, yam, astragalus root, poria cocos, achyranthes root, cistanche, cinnamon, angelica root, wolfberry fruit, deer antler, fennel, white peony root, and licorice has excellent efficacy in treating chemotherapy-induced leukopenia. Based on this, this invention provides a pharmaceutical composition for the prevention and / or treatment of chemotherapy-induced leukopenia and its preparation method, wherein the traditional Chinese medicine composition comprises a combination of the aforementioned ingredients.
[0006] Specifically, in the first aspect, the present invention provides a traditional Chinese medicine composition, the raw materials of which include: red ginseng, prepared rehmannia root, morinda root, tangerine peel, dodder seed, atractylodes rhizome, yam, astragalus root, poria cocos, achyranthes root, cistanche, cinnamon, angelica root, wolfberry fruit, deer antler, fennel, white peony root, and licorice.
[0007] According to the traditional Chinese medicine composition provided by the present invention, the dodder seed is stir-fried dodder seed; And / or, the Atractylodes macrocephala is stir-fried Atractylodes macrocephala; And / or, the Astragalus membranaceus is processed Astragalus membranaceus; And / or, the Cistanche deserticola is processed Cistanche deserticola; And / or, the fennel is salted fennel; And / or, the white peony root is white peony root stir-fried with wine; And / or, the licorice is processed licorice.
[0008] The stir-fried dodder seed (also often recorded as stir-fried dodder seed) is obtained by stir-frying dodder seed using the stir-frying method.
[0009] The stir-fried Atractylodes macrocephala (also often recorded as stir-fried Atractylodes macrocephala) is prepared by processing Atractylodes macrocephala slices or chunks together with auxiliary materials. The auxiliary materials are selected from one or more combinations of hearth soil, talc powder, and wheat bran.
[0010] The processed Astragalus (also often recorded as Astragalus (processed)), also known as "honey-processed Astragalus" or "roasted Astragalus", is a product made by mixing Astragalus slices with refined honey, letting it sit for a while to moisten, and then stir-frying it over a low heat until it is no longer sticky.
[0011] The processed Cistanche deserticola (also often recorded as processed Cistanche deserticola), also known as "wine-processed Cistanche deserticola", is a processed product made by mixing Cistanche deserticola slices with a certain amount of rice wine, letting it soak, and then steaming or stir-frying it.
[0012] Salt-processed fennel (also often recorded as fennel (processed)) is a processed product made by mixing fennel with salt water, letting it sit to moisten, and then stir-frying until dry.
[0013] The aforementioned wine-fried white peony root (also often recorded as white peony root (wine-fried)) is a processed product made by mixing white peony root slices with yellow rice wine, letting it sit for a short time to moisten, and then stir-frying it over a low heat until dry.
[0014] The prepared licorice (also often recorded as prepared licorice), also known as "honey-processed licorice" or "roasted licorice", is a processed product made by mixing licorice slices with refined honey, letting it sit for a while, and then stir-frying it over a low heat until it is no longer sticky.
[0015] Generally speaking, the core purpose of processing Chinese medicine is to reduce toxicity and enhance efficacy, and to harmonize the properties of the medicine. If the medicinal materials are not processed, they are unlikely to exert their ideal therapeutic effects, and may even cause adverse reactions.
[0016] For example, dodder seed: Dodder seed has a pungent, sweet, and neutral flavor, and enters the liver, kidney, and spleen meridians. Its functions include tonifying the liver and kidneys, consolidating essence and reducing urination, calming the fetus, improving eyesight, and stopping diarrhea. Roasted dodder seed is easier to grind and prepare.
[0017] Atractylodes macrocephala: Bitter and sweet in taste, it enters the spleen and stomach meridians. Its functions include strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating and calming the fetus. Stir-frying it can mitigate its drying properties. Furthermore, stir-frying it with wheat bran allows it to enter the middle jiao (middle burner), enhancing its spleen-strengthening and diarrhea-stopping effects.
[0018] Astragalus: Astragalus has a sweet taste and enters the lung and spleen meridians. Its functions include tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, generating fluids and nourishing blood, promoting circulation and relieving pain, promoting pus drainage and detoxification, and promoting tissue regeneration. Its qi-tonifying effect is relatively mild, and it also has the properties of promoting growth and moving to the exterior. Honey-processed astragalus has an enhanced sweet and warm qi-tonifying effect, and it also has the effect of tonifying the middle jiao and replenishing qi, as well as moisturizing dryness.
[0019] Cistanche deserticola: Sweet and salty in taste. It enters the kidney and large intestine meridians, and functions to tonify kidney yang, nourish essence and blood, and moisten the intestines to relieve constipation. Its medicinal properties are slightly drying, with a strong warming effect. After being processed with wine, it becomes sweet and salty in taste, and warm in nature, but not drying, which enhances its warming and tonifying effects on the liver and kidneys, and also improves the circulation of qi and blood.
[0020] Fennel: Fennel has a pungent and warm flavor, and enters the liver, kidney, and spleen meridians. Its functions include dispelling cold, relieving pain, regulating qi, and harmonizing the stomach. After fennel is salted, its pungent and dispersing effects are slightly weakened, while its effects of warming the kidneys, dispelling cold, and relieving pain are enhanced.
[0021] White peony root: White peony root has a bitter and sour taste, and enters the liver and spleen meridians. Its functions include calming the liver and relieving pain, nourishing blood and regulating menstruation, astringing yin and stopping sweating, and its nature is cold. Stir-frying white peony root with wine can mitigate its sour and cold nature, and is good at harmonizing the middle jiao, relieving spasms, softening the liver and relieving pain.
[0022] Licorice: Sweet and neutral in nature, it enters the heart, lung, spleen, and stomach meridians. Its functions include tonifying the spleen and replenishing qi, clearing heat and detoxifying, resolving phlegm and relieving cough, alleviating spasms and pain, and harmonizing other herbs. Honey processing enhances its spleen-tonifying, stomach-strengthening, and qi-replenishing effects.
[0023] If the above-mentioned drugs are not processed, their core efficacy of tonifying the liver and kidneys will be affected. Furthermore, the imbalance of drug properties and the greasy nature of the drugs will exacerbate the disorder of the pathogenesis, increase the risk of the body's tolerance to chemotherapy, and violate the principle of "differentiation of syndromes and treatment, appropriate drug properties, and aiming for balance" in traditional Chinese medicine physiotherapy.
[0024] In this invention, chemotherapy drugs can damage the spleen and stomach, leading to insufficient production of qi and blood, and consequently, directly causing deficiency of essence and blood. Treatment primarily focuses on tonifying the kidneys and strengthening the spleen. According to traditional Chinese medicine theory, processing drugs can enhance their efficacy, reduce the inherent properties of raw drugs, and improve medication safety.
[0025] For example, raw Atractylodes macrocephala is slightly drying, with a stronger effect in drying dampness and promoting diuresis; stir-fried Atractylodes macrocephala has a weaker pungent and dispersing nature, but its spleen-strengthening and qi-tonifying effects are enhanced. Huang Yuanyu pointed out that raw Astragalus membranaceus is slightly cooling, suitable for clearing the exterior and astringing sweat; roasted Astragalus membranaceus is sweet and warm, with enhanced qi-tonifying power, improving its spleen-strengthening and qi-tonifying effects. The spleen is the source of qi and blood production, and sufficient middle qi can promote the transformation of food essence into qi and blood. Raw Paeonia lactiflora is cold in nature, good at clearing heat and astringing yin. After chemotherapy, patients often have blood deficiency and blood stasis, and raw Paeonia lactiflora is not suitable; wine-processed Paeonia lactiflora has a weaker cold nature, and wine can invigorate blood, enhancing its blood-nourishing and blood-invigorating effects. Raw Cistanche deserticola is more inclined to moisten the intestines and promote bowel movements, while processed Cistanche deserticola has enhanced kidney-warming and essence-tonifying effects and is warm without being drying, effectively replenishing the liver and kidney essence and blood depleted by chemotherapy. Raw Fennel is more inclined to warm the middle and regulate qi. After chemotherapy, patients are prone to cold stagnation in the lower jiao; after salt-processing, Fennel guides the medicine to the kidney, enhancing its kidney-warming, cold-dispersing, liver-warming, and pain-relieving effects.
[0026] Although the raw materials of the traditional Chinese medicine composition of this invention are all commonly used drugs in the field, this invention is a summary and refinement based on long-term clinical practice. These 18 traditional Chinese medicines were screened from a large number of related drugs and formulated in a specific ratio to enable each component to exert a synergistic effect, effectively preventing and / or treating leukopenia caused by chemotherapy. In particular, according to the principle that "those who are good at tonifying Yang must seek Yang within Yin, so that Yang can be endlessly generated with the assistance of Yin," this formula combines Rehmannia glutinosa (processed) with deer antler to avoid simply warming Yang and depleting Yin fluids. Red ginseng greatly tonifies the original Qi and strengthens the power of Qi and blood generation; Qi is the commander of blood, and blood is the mother of Qi, so it is combined with Angelica sinensis to take into account both "Qi" and "blood." Furthermore, the dosage of Angelica sinensis is twice that of white peony root (processed with wine), following the principle of "tonifying blood as the main focus and harmonizing blood as the secondary focus." Morinda officinalis and processed Cistanche deserticola assist deer antler in warming and tonifying kidney Yang and strengthening tendons and bones; Lycium barbarum assists Rehmannia glutinosa (processed) in nourishing Yin and liver, achieving a synergistic effect of principal and assistant herbs, tonifying both Yin and Yang, and regulating Qi and blood. The spleen is the source of qi and blood, and the foundation of acquired constitution. The formula uses Atractylodes macrocephala, Dioscorea opposita, and Poria cocos to strengthen the spleen and replenish qi, preventing the cloying and cloying nature of tonifying herbs like Rehmannia glutinosa and deer antler from hindering digestion. Tangerine peel regulates qi and invigorates the spleen, preventing the stagnation caused by tonifying herbs. Cinnamon warms and tonifies kidney yang, guiding fire back to its source; salted fennel warms the kidneys, dispels cold, regulates qi, and harmonizes the stomach; Achyranthes bidentata guides the medicine downwards; stir-fried Cuscuta chinensis assists the principal and assistant herbs in consolidating kidney essence; and licorice harmonizes all the herbs. Furthermore, the dosage of cinnamon and salted fennel is mild, embodying the principle of "generating qi with a little fire," suitable for patients with weakened constitutions after chemotherapy.
[0027] According to the traditional Chinese medicine composition provided by the present invention, the traditional Chinese medicine composition comprises, by weight parts: 145-155 parts of red ginseng, 295-305 parts of prepared rehmannia root, 145-155 parts of morinda root, 70-80 parts of dried tangerine peel, 145-155 parts of stir-fried dodder seed, 70-80 parts of stir-fried atractylodes macrocephala, 145-155 parts of yam, 95-105 parts of prepared astragalus root, 145-155 parts of poria cocos, 95-105 parts of achyranthes bidentata, 145-155 parts of prepared cistanche deserticola, 95-105 parts of cinnamon, 145-155 parts of angelica sinensis, 95-105 parts of wolfberry fruit, 70-80 parts of deer antler, 70-80 parts of salt-processed fennel, 70-80 parts of wine-fried white peony root, and 45-55 parts of prepared licorice root.
[0028] According to the traditional Chinese medicine composition provided by the present invention, the traditional Chinese medicine composition comprises, by weight parts: 150 parts red ginseng, 300 parts prepared rehmannia root, 150 parts morinda root, 75 parts tangerine peel, 150 parts stir-fried dodder seed, 75 parts stir-fried atractylodes rhizome, 150 parts yam, 100 parts prepared astragalus root, 150 parts poria cocos, 100 parts achyranthes root, 150 parts prepared cistanche deserticola, 100 parts cinnamon, 150 parts angelica root, 100 parts wolfberry fruit, 75 parts deer antler, 75 parts salt-processed fennel, 75 parts stir-fried white peony root with wine, and 50 parts prepared licorice root.
[0029] Secondly, the present invention also provides the use of the traditional Chinese medicine composition described above in the prevention and / or treatment of leukopenia caused by chemotherapy.
[0030] Thirdly, the present invention also provides a method for preparing a medicament for preventing and / or treating chemotherapy-induced leukopenia, comprising: the traditional Chinese medicine composition as described above.
[0031] According to the preparation method provided by the present invention, the chemotherapy is a chemotherapy using fluorouracil drugs.
[0032] The drug is prepared for use in combination with the chemotherapy drug 5-fluorouracil, and is administered before, during, or after administration of the chemotherapy drug.
[0033] According to the preparation method provided by the present invention, the drug is used to promote the proliferation of lymphocytes and / or monocytes.
[0034] The experiment verified that the drug increases the white blood cell level of the subjects by promoting the proliferation of lymphocytes and / or monocytes.
[0035] According to the preparation method provided by the present invention, the drug is an oral formulation.
[0036] The oral formulation may be, for example, a tablet, capsule, or granule.
[0037] The drug may consist of a traditional Chinese medicine composition and a pharmaceutically acceptable carrier; The pharmaceutically acceptable carrier refers to a conventional drug carrier in the pharmaceutical field, selected from one or more of the following: fillers, binders, disintegrants, lubricants, solubilizers, suspending agents, wetting agents, pigments, fragrances, solvents, surfactants, or flavoring agents.
[0038] The filler is selected from starch, pregelatinized starch, dextrin, glucose, sucrose, lactose, lactitol, microcrystalline cellulose, mannitol, sorbitol or xylitol, preferably sorbitol, microcrystalline cellulose, lactose or pregelatinized starch; The disintegrant is selected from crospovidone sodium carboxymethyl cellulose, crospovidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch or starch, preferably crospovidone, low-substituted hydroxypropyl cellulose or sodium carboxymethyl starch; The lubricant is selected from magnesium stearate, talc, micronized silica gel, PEG4000, PEG6000, sodium lauryl sulfate, with magnesium stearate and talc being preferred. The adhesive is selected from sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, povidone, starch paste, sucrose, powdered sugar, glue, gelatin, and polyethylene glycol, with hydroxypropyl methyl cellulose and povidone being preferred. The solubilizer is selected from sodium hydroxide, potassium hydroxide, sodium bicarbonate, meglumine, L-lysine, and L-arginine, with sodium hydroxide and meglumine being preferred. The suspending agent is selected from micronized silica gel, beeswax, cellulose, and solid polyethylene glycol; The wetting agent is selected from glycerin, Tween-80, ethoxylated castor oil or lecithin; The solvent is selected from ethanol, liquid polyethylene glycol, isopropanol, Tween-80, glycerin, propylene glycol or vegetable oil, and the vegetable oil is selected from soybean oil, castor oil, peanut oil, blended oil, etc. The surfactant is selected from sodium dodecylbenzenesulfonate, stearic acid, polyoxyethylene-polyoxypropylene copolymer, fatty acid sorbitan, or polysorbate (Tween), etc. The flavoring agent is selected from aspartame, sucralose, flavoring, stevia, acesulfame potassium, citric acid, or sodium saccharin.
[0039] According to the preparation method provided by the present invention, the dosage of the drug, converted to the human equivalent dose for rats, is 2.0 g / kg.
[0040] Fourthly, the present invention also provides a medicament for preventing and / or treating chemotherapy-induced leukopenia, which is prepared by the method described above.
[0041] Chemotherapy patients often suffer from "deficiency of both qi and blood, weakness of the spleen and kidneys, and stagnation of cold pathogens." This invention provides a pharmaceutical composition and its preparation method for preventing and / or treating chemotherapy-induced leukopenia. Through the combined effects of red ginseng, prepared rehmannia root, morinda root, tangerine peel, dodder seed, atractylodes rhizome, yam, astragalus root, poria cocos, achyranthes root, cistanche, cinnamon, angelica root, wolfberry fruit, deer antler, fennel, white peony root, and licorice, taking some components as examples, ginseng in the formula greatly replenishes vital energy and is a key medicine for treating prolonged blood loss and summer heat-induced qi deficiency; it is a core and indispensable ingredient in this formula. Furthermore, the Qing Dynasty medical text *Ben Cao Zheng* states that yam "strengthens the spleen and replenishes deficiency, nourishes essence and strengthens the kidneys, treats various deficiencies and injuries, and heals the five types of fatigue and seven types of injury." This medicine enters the lung and stomach meridians, calming the spirit; combined with atractylodes rhizome, poria cocos, and licorice, which tonify the spleen, it is an excellent medicine for treating various deficiency-related diseases and is indispensable in this formula. After being processed with salt, fennel seeds guide the medicine to the kidneys. Their warm nature allows them to warm the kidneys, dispel cold, regulate qi, and harmonize the stomach. They not only enhance the warming and nourishing effects of yang-tonifying herbs like deer antler and Morinda officinalis, improving spleen and kidney yang deficiency after chemotherapy, but also regulate qi and relieve chest congestion, mitigating the cloying nature of tonifying herbs like Rehmannia glutinosa and Cistanche deserticola, preventing "tonification from hindering the stomach," and aiding the spleen and stomach in the digestion and absorption of tonifying drugs. As a key component of this formula, the herbal composition of this invention achieves the prevention and / or treatment of chemotherapy-induced leukopenia. Specifically, it is used in combination with the chemotherapy drug 5-fluorouracil, administered before, during, or after chemotherapy drug administration, to increase the subject's white blood cell level by promoting the proliferation of lymphocytes and / or monocytes. Attached Figure Description
[0042] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0043] Figure 1 This describes the specific process of administering the corresponding drug via gavage in Test Example 1 provided by the present invention. Detailed Implementation
[0044] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.
[0045] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels. The preparation process for some raw materials is as follows: Preparation Example 1 A method for preparing stir-fried dodder seeds, the process of which is as follows: take clean dodder seeds, place them in a stir-frying container, heat them over a low flame, stir-fry until they make a slight popping sound, at which point the surface turns yellow and releases a fragrance, remove them and let them cool.
[0046] Preparation Example 2 A method for preparing stir-fried Atractylodes macrocephala, the process is as follows: first heat the pot, sprinkle in wheat bran (the amount is 10% of the weight of Atractylodes macrocephala), when it smokes, put in the slices of Atractylodes macrocephala, stir constantly, stir-fry until the surface of Atractylodes macrocephala is dark yellow or dark brown and a caramel aroma is released, take it out, sift out the wheat bran, and let it cool.
[0047] Preparation Example 3 A method for preparing Astragalus membranaceus, the process is as follows: take refined honey (the amount used is 25% of the weight of Astragalus membranaceus), dilute it with an appropriate amount of boiling water, pour it into clean Astragalus membranaceus slices and mix well, let it sit to moisten, place it in a frying container, heat it over a low heat, fry until it is no longer sticky, take it out and let it cool.
[0048] Preparation Example 4 A method for preparing Cistanche deserticola, the process is as follows: take clean Cistanche deserticola slices, mix them with rice wine (the amount is 30% of the weight of Cistanche deserticola), put them in a sealed container to moisten until the wine is absorbed, put them in a steamer and steam until the surface turns black (about 6-8 hours), take them out and sun dry or oven dry.
[0049] Preparation Example 5 A method for preparing salted fennel seeds, the process of which is as follows: take clean fennel seeds, mix them with salt water (the amount of salt is 2% of the weight of fennel seeds), let them soak, place them in a frying container, heat them over a low heat, fry them until they turn slightly yellow, remove them, and let them cool.
[0050] Preparation Example 6 A method for preparing stir-fried white peony root with wine, the process is as follows: take clean white peony root slices, mix them with yellow wine (the amount is 10% of the weight of white peony root), let them sit for a while, put them in a stir-frying container, heat them over a low heat, stir-fry until slightly dry, take them out, and let them cool.
[0051] Preparation Example 7 A method for preparing licorice, the process is as follows: take refined honey (the amount used is 25% of the weight of licorice), dilute it with an appropriate amount of boiling water, pour it into clean licorice slices and mix well, let it sit to moisten, place it in a frying container, heat it over a low heat, fry it until it turns dark yellow and is no longer sticky, take it out and let it cool.
[0052] Example 1 A traditional Chinese medicine composition, comprising: 150g red ginseng, 300g prepared rehmannia root, 150g morinda root, 75g dried tangerine peel, 150g stir-fried dodder seed, 75g stir-fried atractylodes macrocephala, 150g yam, 100g prepared astragalus root, 150g poria cocos, 100g achyranthes bidentata, 150g prepared cistanche deserticola, 100g cinnamon, 150g angelica sinensis, 100g wolfberry, 75g deer antler, 75g salt-processed fennel, 75g stir-fried white peony root with wine, and 50g prepared licorice root.
[0053] Test Example 1: Animal Experiment (1) Model preparation and grouping of drugs SPF-grade male Wistar rats. After 4 days of acclimatization, they were randomly divided into 5 groups of 8 rats each: Blank control group; Model group; The high-dose group of the traditional Chinese medicine composition in Example 1; Dosage group of the traditional Chinese medicine composition in Example 1; The low-dose group of the traditional Chinese medicine composition in Example 1.
[0054] After 5 days of gavage administration of the corresponding drugs (the blank control group and the model group were given drinking water), 5-FU (100 mg / kg) was injected intraperitoneally once daily for 4 consecutive days (the blank control group was given physiological saline intraperitoneally). Drug administration continued concurrently with model establishment. Samples were collected 24 hours after the last administration. The specific procedure is as follows: Figure 1 As shown.
[0055] The dosage and concentration of each group of drugs are shown in Table 1 below.
[0056] Table 1 (2) Detection method (2.1) Weight detection: The weight of rats was measured and recorded on D0, D5, D7 and D9 respectively, and the weight gain of each group of animals after the start of chemotherapy was statistically analyzed.
[0057] (2.2) Whole blood white blood cell count: Rats were anesthetized by intraperitoneal injection, blood was collected from the abdominal aorta, anticoagulated with EDTA, and the whole blood white blood cell count was detected by a blood cell analyzer.
[0058] (3) Test results (3.1) Weight gain The experimental results are shown in Table 2 below.
[0059] Table 2 Effects on body weight gain in rats with chemotherapy-induced (5-Fu) leukopenia (g, expressed as mean) Table 2 shows the comparison with the blank control group. ** This indicates that p < 0.01.
[0060] As can be seen from Table 2: Compared with the blank control group, there was no significant change in the weight gain of each group on day 5 (p>0.05), but the weight gain of each group decreased significantly on days 7 and 9 (p<0.01).
[0061] Compared with the model group, on day 5, the weight gain of rats in the high- and medium-dose groups of the traditional Chinese medicine composition of Example 1 showed an increasing trend, but no statistical difference was observed (all p > 0.05); on days 7 and 9, the weight gain of rats in the high-, medium-, and low-dose groups of the traditional Chinese medicine composition of Example 1 all showed an increasing trend, but no statistical difference was observed (all p > 0.05).
[0062] (3.2) Whole blood white blood cell count The experimental results are shown in Table 3 below. WBC represents white blood cell count, LYM represents lymphocytes, MON represents monocytes, and NEUT represents neutrophils.
[0063] Table 3 Effects on white blood cell count and differential in rats with chemotherapy-induced (5-Fu) leukopenia (expressed as mean value). Table 3 shows the comparison with the blank control group. * This indicates that p < 0.05. ** This indicates p < 0.01; compared with the model group. # This indicates that p < 0.05. ## This indicates that p < 0.01.
[0064] Compared with the blank control group, the whole blood WBC count of rats in each group was significantly decreased (all p<0.01); compared with the model group, the whole blood WBC count of rats in the high-dose group of the traditional Chinese medicine composition in Example 1 was significantly increased (p<0.05), and the whole blood WBC count of rats in the medium and low-dose groups of the traditional Chinese medicine composition in Example 1 showed an increasing trend, but no statistical difference was observed (all p>0.05).
[0065] Compared with the blank control group, the whole blood LYM count of rats in each group was significantly reduced (all p<0.01); compared with the model group, the whole blood LYM count of rats in the medium dose group of the traditional Chinese medicine composition in Example 1 was significantly increased (p<0.05), and the whole blood LYM count of rats in the high and low dose groups of the traditional Chinese medicine composition in Example 1 showed an increasing trend, but no statistical difference was observed (all p>0.05).
[0066] Compared with the blank control group, the whole blood MON count of rats in each group showed a significant decreasing trend (p>0.05); compared with the model group, the whole blood MON count of rats in the high-dose group of the traditional Chinese medicine composition in Example 1 was significantly increased (p<0.05), while the whole blood MON count of rats in the medium and low-dose groups of the traditional Chinese medicine composition in Example 1 did not show significant changes (both p>0.05).
[0067] Compared with the blank control group, there was no significant change in the whole blood NEUT count of rats in the model group (p>0.05); compared with the model group, the whole blood NEUT count of rats in the high-dose group of the traditional Chinese medicine composition in Example 1 showed a significant increasing trend, but no statistical difference was observed (p>0.05); the whole blood NEUT count of rats in the medium and low-dose groups of the traditional Chinese medicine composition in Example 1 did not show significant changes (both p>0.05).
[0068] Test Example 2: Lymphocyte Proliferation Experiment (1) Primary spleen lymphocyte culture Aseptically remove the spleen. Draw 1 ml of Hanks buffer into a syringe and inject it into the spleen along its long axis. Inject 2 ml of Hanks buffer into a sterile glass petri dish and squeeze out the spleen cells. Slightly tilt and let stand for 1-2 minutes (to allow spleen residue to settle). Aspirate the supernatant from the spleen cell suspension and centrifuge at 3000 rpm for 3 minutes, then aspirate the supernatant. Using a 200 μl pipette, aspirate the Hanks buffer to disperse the lymphocytes in the middle layer, and transfer approximately 2 ml of the supernatant to a new 15 ml Eppendorf tube. Add 3 times the volume of erythrocyte lysis buffer (approximately 6 ml), gently vortex or invert to mix, and incubate on ice for 15 minutes, mixing twice during this period. Centrifuge at 450 g for 10 minutes at 4°C to pellet the lymphocytes. Repeat this process twice. Resuspend the cells in 2 ml of culture medium. Add 2 ml of culture medium to a cell culture flask, add the spleen cell suspension to the flask, mix well, and incubate at 37°C in a CO2 incubator for later use.
[0069] (2) Preparation of drug-containing serum from the traditional Chinese medicine composition of Example 1 Twenty SPF-grade SD rats, 7-8 weeks old and weighing 220-240g, were randomly divided into a blank control group and a group containing the traditional Chinese medicine composition of Example 1, with 10 rats in each group, after 3-5 days of acclimatization.
[0070] The equivalent dose of the test drug in humans and rats, calculated based on body surface area, is 2 g / (kg•d). The test drug suspension with a concentration of 200 mg / ml is prepared by adding distilled water and set aside for later use.
[0071] In Example 1, the rats in the traditional Chinese medicine composition group were administered the drug orally twice daily at a volume of 10 mL / kg for 3 consecutive days.
[0072] The blank control group rats were given an equal volume of distilled water.
[0073] One hour after administration on the morning of the 4th day (with fasting but no water restriction for 12 hours prior to administration), anesthesia was administered via intraperitoneal injection of 50 mg / kg of 1.0% sodium pentobarbital. Blood was then drawn from the abdominal aorta and allowed to stand for 2 hours. After centrifugation at 3500 r / min for 10 min (centrifugation radius of 10 cm), the serum was collected, inactivated in a water bath at 56℃ for 30 min, aseptically aliquoted, and stored at -80℃ for later use.
[0074] (3) Lymphocyte proliferation experiment Primary mouse spleen lymphocytes, adjusted to a cell concentration of 2×10⁻⁶. 6 / ml, take 100μl / well of a 96-well culture plate, and incubate overnight at 37℃. Dissolve LPS in PBS and adjust the concentration to 0.1mg / ml for later use. Grouping and administration methods are as follows: ① Blank control group: 100 μl / well of 10% FBS was added; ② Model group: 10 μl / well of LPS (final concentration of 5 μg / ml) + 90 μl / well of 10% FBS; ③ Blank serum group: 10 μl / well of LPS was added + 90 μl / well of 30% rat blank serum was added; ④ The traditional Chinese medicine composition containing serum from Example 1: 10 μl / well of LPS was added and 90 μl / well of serum containing 30% concentration of the traditional Chinese medicine composition from Example 1 was added.
[0075] Each group had 6 replicates. After culturing for 24 hours, 10 μl of CCK-8 solution was added to each well, and the cells were cultured for another 2 hours. The absorbance was measured at 450 nm, and the cell proliferation rate was calculated. Cell proliferation rate (%) = D(λ) drug administration wells / D(λ) blank control wells × 100%.
[0076] (4) Experimental results The test results are shown in Table 4 below.
[0077] Table 4. Effects of drug-containing serum on LPS-induced splenic lymphocyte proliferation (expressed as mean value) In Table 4, # is compared with the blank control group. ## This indicates that P < 0.01. ### This indicates that P < 0.001; * Compared with the blank serum group, *** This means P < 0.001.
[0078] As shown in Table 4, the proliferation rate of spleen lymphocytes after LPS induction was 115.48%, which was statistically different from that of the normally cultured blank control group. p <0.01); Rat blank serum had a certain inhibitory effect on LPS-induced splenic lymphocyte proliferation, with a cell proliferation rate of 90.50%, which was significantly lower than that of the blank control group ( p <0.001); After administration of the serum containing the traditional Chinese medicine composition of Example 1, the lymphocyte proliferation rate increased to 155.05%, which was significantly different from that of the rat blank serum group ( p <0.001), indicating that the serum containing the traditional Chinese medicine composition of Example 1 can promote LPS-induced proliferation of splenic lymphocytes.
[0079] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. A traditional Chinese medicine composition, characterized in that, The raw materials include: red ginseng, prepared rehmannia, baiji- tian, dried tangerine or orange peel, cuscuta, white atractylodes, Chinese yam, milk- vetch root, poria, cyathula, cistanche, cassia, angelica, medlar, pilose asiabell y, cumin, white peony root, and licorice.
2. The traditional Chinese medicine composition according to claim 1, characterized in that, The cuscuta is stir-fried cuscuta; And / or, the white atractylodes is stir-fried white atractylodes; And / or, the milk-vetch root is processed milk-vetch root; And / or, the cistanche is processed cistanche; And / or, the cumin is salt-processed cumin; And / or, the white peony root is wine-stir-fried white peony root; And / or, the licorice is processed licorice.
3. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition comprises, by weight fraction: red ginseng 145-155 parts, prepared rehmannia 295-305 parts, baiji-tian 145-155 parts, dried tangerine or orange peel 70-80 parts, stir-fried cuscuta 145-155 parts, stir-fried white atractylodes 70-80 parts, Chinese yam 145-155 parts, processed milk-vetch root 95-105 parts, poria 145-155 parts, cyathula 95-105 parts, processed cistanche 145-155 parts, cassia 95-105 parts, angelica 145-155 parts, medlar 95-105 parts, pilose asiabell y 70-80 parts, salt-processed cumin 70-80 parts, wine-stir-fried white peony root 70-80 parts, and processed licorice 45-55 parts.
4. The traditional Chinese medicine composition according to claim 3, characterized in that, The traditional Chinese medicine composition comprises, by weight fraction: red ginseng 150 parts, prepared rehmannia 300 parts, baiji-tian 150 parts, dried tangerine or orange peel 75 parts, stir-fried cuscuta 150 parts, stir-fried white atractylodes 75 parts, Chinese yam 150 parts, processed milk-vetch root 100 parts, poria 150 parts, cyathula 100 parts, processed cistanche 150 parts, cassia 100 parts, angelica 150 parts, medlar 100 parts, pilose asiabell y 75 parts, salt-processed cumin 75 parts, wine-stir-fried white peony root 75 parts, and processed licorice 50 parts.
5. The traditional Chinese medicine composition of any one of claims 1-4 for use in preventing and / or treating leukopenia caused by chemotherapy.
6. A method for preparing a medicament for preventing and / or treating leukopenia caused by chemotherapy, characterized by, comprising: The traditional Chinese medicine composition of any one of claims 1-4.
7. The preparation method according to claim 6, characterized in that, The chemotherapy is chemotherapy using fluorouracil drugs.
8. The preparation method according to claim 6 or 7, characterized in that, The drug is used for promoting proliferation of lymphocytes and / or monocytes.
9. The method of any one of claims 6 to 8, wherein the method further comprises the step of: The drug is an oral preparation.
10. A medicament for preventing and / or treating chemotherapy-induced leukopenia, characterized by, The drug is prepared by the preparation method of any one of claims 5-9. The traditional Chinese medicine composition comprises, by weight fraction: red ginseng 145-155 parts, prepared rehmannia 295-305 parts, baiji-tian 145-155 parts, dried tangerine or orange peel 70-80 parts, stir-fried cuscuta 145-155 parts, stir-fried white atractylodes 70-80 parts, Chinese yam 145-155 parts, processed milk-vetch root 95-105 parts, poria 145-155 parts, cyathula 95-105 parts, processed cistanche 145-155 parts, cassia 95-105 parts, angelica 145-155 parts, medlar 95-105 parts, pilose asiabell y 70-80 parts, salt-processed cumin 70-80 parts, wine-stir-fried white peony root 70-80 parts, and processed licorice 45-55 parts.