Rhizoma atractylodis macrocephalae preparation and application thereof

Abstract

The invention discloses a rhizoma atractylodis macrocephalae preparation and application thereof, belongs to the technical field of medical medicines, and particularly relates to a rhizoma atractylodis macrocephalae preparation formed by compounding a rhizoma atractylodis macrocephalae active matter and an auxiliary agent. Atractylodes macrocephala koidz rhizomes are cleaned and dried to prepare atractylodes macrocephala koidz powder, the atractylodes macrocephala koidz powder is subjected to reflux extraction treatment by mixing with water, reflux extraction treatment by mixing with an alcohol solution and steam distillation treatment by mixing with water to obtain an atractylodes macrocephala koidz water extraction product, an atractylodes macrocephala koidz alcohol extraction product and an atractylodes macrocephala koidz water distillation product, and the atractylodes macrocephala koidz preparation is prepared by mixing the products. An auxiliary agent can be added to be compounded with the bighead atractylodes rhizome active matter, and microbial lipopeptide, lipopeptide derivatives, medical solvents and the like can be used as the auxiliary agent. The rhizoma atractylodis macrocephalae preparation can prevent and treat peripheral nerve injury caused by tumor drugs, promote repair of peripheral nerve apoptosis caused by anti-tumor drugs, promote the neurotrophic factor expression level of nerve cells and promote repair and regeneration of nervous tissues.

Description

Technical Field

[0001] This invention belongs to the field of medical pharmaceutical technology, specifically relating to a preparation of Atractylodes macrocephala and its uses. Background Technology

[0002] Anti-tumor drugs play a crucial role in cancer treatment, but their side effects cannot be ignored, especially chemotherapy-induced peripheral neuropathy (CIPN). CIPN is damage to the peripheral nervous system caused by chemotherapy drugs, mainly manifesting as numbness, pain, and paresthesia in the limbs, severely impacting patients' quality of life and treatment outcomes. Currently, Western medicine treats CIPN primarily with symptomatic relief, lacking specific drugs, while traditional Chinese medicine shows unique advantages in alleviating CIPN.

[0003] CIPN is a common dose-limiting toxicity of chemotherapy, with an incidence rate as high as 70%. Platinum-based drugs (such as cisplatin and oxaliplatin) and taxanes are the main causative agents of CIPN. The pathogenesis of CIPN is not fully understood, but it may be related to oxidative stress, mitochondrial dysfunction, inflammatory response, and nerve axon damage. The clinical manifestations of CIPN are diverse, including sensory abnormalities (such as numbness and tingling), motor disorders (such as muscle weakness), and autonomic dysfunction (such as constipation and dizziness). These symptoms not only reduce patients' quality of life but may also lead to a reduction or interruption of chemotherapy dosage, thus affecting the efficacy of cancer treatment. Currently, Western medicine treats CIPN primarily with symptomatic relief, commonly using analgesics, antidepressants, and anticonvulsants; however, these drugs have limited efficacy and may cause side effects. Therefore, developing safe and effective treatment methods is a current research focus.

[0004] Traditional Chinese medicine (TCM) theory considers CIPN to fall under the category of "Bi syndrome," and its pathogenesis is closely related to deficiency of Qi and blood, stagnation of cold pathogens, and obstruction of the meridians by blood stasis. TCM can effectively alleviate CIPN symptoms through its effects of harmonizing Qi and blood, warming the meridians and promoting blood circulation, and removing blood stasis. In recent years, numerous studies have confirmed the efficacy of compound TCM formulas (such as the modified Huangqi Guizhi Wuwu Decoction) in improving CIPN symptoms. Furthermore, single-herb extracts of TCM (such as Angelica sinensis, Astragalus membranaceus, and Spatholobus suberectus) have also been shown to have neuroprotective effects. However, existing research mainly focuses on compound TCM formulas, with relatively insufficient research on single herbs and their active ingredients.

[0005] Currently, the main preventative measure for peripheral neuropathy caused by antitumor drugs is ice gloves, while clinical treatment primarily involves observation and symptomatic relief. Ice gloves are the primary preventative measure in clinical practice to reduce blood flow to the limbs, thereby mitigating the damage of antitumor drugs to the nervous system. However, for patients already experiencing peripheral neuropathy caused by antitumor drugs, oral neurotrophic drugs are the main treatment, but the therapeutic effect is unsatisfactory. Summary of the Invention

[0006] The purpose of this invention is to provide a preparation of Atractylodes macrocephala that increases blood vessel diameter, blood velocity, vascular pulsatility index, reduces peripheral blood inflammatory factors, can prevent and treat peripheral nerve damage caused by tumor drugs, promote the repair of peripheral nerve apoptosis induced by anti-tumor drugs, promote the expression level of neurotrophic factors in nerve cells, and promote the repair and regeneration of nerve tissue, as well as its uses.

[0007] The purpose of this invention is to provide an application of Atractylodes macrocephala extract in the prevention and treatment of peripheral neuropathy caused by antitumor drugs, providing a safe, effective and economical new method for the prevention and treatment of peripheral neuropathy caused by antitumor drugs in clinical practice.

[0008] The technical solution adopted by the present invention to achieve the above objectives is as follows: A preparation of Atractylodes macrocephala, comprising: active ingredient of Atractylodes macrocephala and excipients, wherein the amount of excipients used is 0.01-150 wt% of the active ingredient of Atractylodes macrocephala. Clinical trials of this invention have shown that topical application of Atractylodes macrocephala extract can significantly improve peripheral neuropathy and inflammatory damage to peripheral nerve tissue caused by antitumor chemotherapy drugs, improve nerve conduction velocity and inflammatory damage in peripheral nerve tissue, and promote nerve cell growth.

[0009] Atractylodes macrocephala preparations protect peripheral nerve tissue damaged by anti-tumor chemotherapy drugs, promote the repair and proliferation of nerve tissue, and inhibit the inflammatory damage and apoptosis of peripheral nerves caused by anti-tumor chemotherapy drugs, thereby protecting peripheral nerve tissue from apoptosis.

[0010] This invention provides a safe, effective, and economical new method for the prevention and treatment of peripheral neuropathy caused by antitumor chemotherapy drugs in clinical practice.

[0011] Preferably, the active ingredient of Atractylodes macrocephala includes at least one of the following: Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala water vapor extract.

[0012] More preferably, the active ingredients of Atractylodes macrocephala are Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala water vapor extract; The amount of Atractylodes macrocephala alcohol extract used is 50-150 vol of Atractylodes macrocephala water extract used; or, the amount of Atractylodes macrocephala steamed product used is 50-150 vol of Atractylodes macrocephala water extract used.

[0013] More preferably, in the preparation of the Atractylodes macrocephala water extract, Atractylodes macrocephala is mixed with water and extracted by reflux to obtain the Atractylodes macrocephala water extract; or, In the preparation of the Atractylodes macrocephala ethanol extract, Atractylodes macrocephala is mixed with an alcohol solution and extracted by reflux to obtain the Atractylodes macrocephala ethanol extract; or, In the preparation of Atractylodes macrocephala water distillation product, Atractylodes macrocephala is mixed with water and then steam distilled to obtain the Atractylodes macrocephala water distillation product.

[0014] Preferably, in the preparation of Atractylodes macrocephala powder, the rhizomes of Atractylodes macrocephala are washed, dried, and then crushed to 20-40 mesh using a pulverizer to obtain Atractylodes macrocephala powder. In the drying process, the rhizomes of Atractylodes macrocephala are dried until the moisture content is below 8%.

[0015] Preferably, in the preparation of the Atractylodes macrocephala water extract, Atractylodes macrocephala powder is mixed with pure water, refluxed at 90-100℃ for 2-8 hours, the residue is removed by filtration, concentrated to 10-30 vol% at 20-60℃, ethanol is added and allowed to stand to precipitate polysaccharides, the supernatant is collected by centrifugation, and the Atractylodes macrocephala water extract is obtained.

[0016] More preferably, in the preparation of the Atractylodes macrocephala water extract, the amount of Atractylodes macrocephala powder used is 5-15 wt% of pure water, and the amount of ethanol used is 400-600 wt% of pure water.

[0017] Preferably, in the preparation of the Atractylodes macrocephala ethanol extract, Atractylodes macrocephala powder is mixed with an ethanol solution, refluxed at 60-80℃ for 2-8 hours, the residue is removed by filtration, and the ethanol is concentrated and recovered to obtain the Atractylodes macrocephala ethanol extract.

[0018] More preferably, in the preparation of the Atractylodes macrocephala ethanol extract, the ethanol solution is a mixture of ethanol and water, and the ethanol content in the ethanol solution is 60-70 wt%.

[0019] More preferably, in the preparation of Atractylodes macrocephala ethanol extract, the amount of Atractylodes macrocephala powder used is 5-25 wt% of the ethanol solution.

[0020] Preferably, in the preparation of the Atractylodes macrocephala water-distilled product, Atractylodes macrocephala powder is mixed with pure water, steam distilled for 2-8 hours, the volatile oil is collected by oil-water separation, and dehydrated with anhydrous sodium sulfate to obtain the Atractylodes macrocephala water-distilled product.

[0021] More preferably, in the preparation of the Atractylodes macrocephala water-distilled product, the amount of Atractylodes macrocephala powder used is 10-30 wt% of pure water.

[0022] This invention discloses a method for preparing a preparation of Atractylodes macrocephala, which involves mixing active ingredients of Atractylodes macrocephala to obtain the preparation.

[0023] Preferably, the active ingredients of Atractylodes macrocephala include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract and Atractylodes macrocephala water vapor extract, wherein the amount of Atractylodes macrocephala alcohol extract used is 50-150 vol% of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala water vapor extract used is 50-150 vol% of Atractylodes macrocephala water extract.

[0024] Preferably, the excipients include at least one of water, alcohol, ester, ether and biological agents.

[0025] More preferably, the alcohol agent includes at least one selected from methanol, ethanol, propylene glycol, isopropanol, ethylene glycol, and polyethylene glycol; or, Ethers include at least one of diethyl ether, diethylene glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol diethyl ether, ethylene glycol monobutyl ether, and ethylene glycol dibutyl ether; or, Ester agents include at least one of polyethylene glycol laurate, propylene glycol laurate, and glyceryl caprylate; or, Biological agents include at least one of microbial lipopeptides, lipopeptide derivatives, polypeptides, and polypeptide derivatives.

[0026] Atractylodes macrocephala active ingredients can reduce neurological inflammation induced by antitumor drugs, protect nerve cells from inflammatory death, and activate the transmission of neurotrophic growth factor (NGF) in nerve cells, thus protecting nerve cells from neurological damage. When microbial lipopeptides and / or lipopeptide derivatives are combined with Atractylodes macrocephala active ingredients to form Atractylodes macrocephala preparations, these preparations exhibit even better effects, demonstrating superior efficacy in reducing neurological inflammation induced by antitumor drugs, protecting nerve cells from inflammatory death, activating the transmission of NGF in nerve cells, and protecting nerve cells from neurological damage.

[0027] More preferably, the excipient is a microbial lipopeptide, which is isolated from Bacillus licheniformis through fermentation culture.

[0028] More preferably, in the preparation of microbial lipopeptides, Bacillus licheniformis strain is inoculated into the fermentation medium at an inoculation amount of 1% by volume, cultured for 0.5-7 days, centrifuged to separate the bacterial cells and supernatant, the bacterial cells are broken to obtain the lysate, the supernatant and the lysate are mixed, extracted with an extractant, the organic phase is separated, vacuum distilled, and freeze-dried to obtain microbial lipopeptides.

[0029] More preferably, in the preparation of microbial lipopeptides, the fermentation medium contains 20 g / L corn steep liquor, 20 g / L glucose, 3 g / L sodium gluconate, 2 g / L yeast extract, 2 g / L ammonium sulfate, 2 g / L disodium hydrogen phosphate, 2 g / L dipotassium hydrogen phosphate, 2 g / L calcium chloride, 1 g / L calcium carbonate, 0.5 g / L magnesium sulfate, 0.5 g / L potassium chloride, and 0.03 g / L ferric chloride. The pH is adjusted to neutral, and the remainder is water. The bacterial cells are disrupted using an ultrasonic disruptor at a temperature of 25°C and a frequency of 25 kHz. The extraction solvent is dichloromethane.

[0030] More preferably, the excipient is a lipopeptide derivative, which is derived from microbial lipopeptides and a derivatizing agent.

[0031] More preferably, in the preparation of the lipopeptide derivative, the derivatizing agent is mixed with deionized water, the pH is adjusted to 4-6, an EDC / NHSS solution is added and stirred, the mixture is treated at 30-50℃ for 10-60 min, then microbial lipopeptides are added, and the reaction is carried out at 30-50℃ for 2-8 h. After the reaction is completed, EDC and NHSS are removed by ultrafiltration, and the mixture is freeze-dried to obtain the lipopeptide derivative.

[0032] More preferably, in the preparation of the lipopeptide derivative, the derivatizing agent includes D-glucosamine and N,N-dimethylglycine, wherein the amount of D-glucosamine used is 0.05-0.5 wt% of deionized water, and the amount of N,N-dimethylglycine used is 20-100 wt% of D-glucosamine. More preferably, in the preparation of the lipopeptide derivative, the amount of EDC used is 10-50 wt% of D-glucosamine.

[0033] More preferably, in the preparation of the lipopeptide derivative, the amount of NHSS used is 10-50 wt% of D-glucosamine.

[0034] More preferably, in the preparation of the lipopeptide derivative, the amount of microbial lipopeptide used is 400-1000 wt% of D-glucosamine.

[0035] More preferably, the derivatizing agent includes D-glucosamine and / or N,N-dimethylglycine.

[0036] More preferably, the excipients include medical solvents or pharmaceutical solvents.

[0037] The present invention also discloses a preparation of Atractylodes macrocephala preparation, wherein the active ingredient of Atractylodes macrocephala is mixed with an excipient to obtain the preparation.

[0038] Preferably, the active ingredients of Atractylodes macrocephala include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract and Atractylodes macrocephala water vapor extract, wherein the amount of Atractylodes macrocephala alcohol extract used is 50-150 vol% of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala water vapor extract used is 50-150 vol% of Atractylodes macrocephala water extract.

[0039] Preferably, the amount of excipient used is 0.02-150 wt% of the active ingredient of Atractylodes macrocephala.

[0040] More preferably, the excipient includes microbial lipopeptides, and the amount of microbial lipopeptides used is 0.5-10 wt% of the active ingredient of Atractylodes macrocephala.

[0041] More preferably, the excipients include lipopeptide derivatives, and the amount of lipopeptide derivatives used is 0.5-10 wt% of the active ingredient of Atractylodes macrocephala.

[0042] More preferably, the excipient includes 2-acetamido-2-deoxy-D-galactosamide, and the amount of 2-acetamido-2-deoxy-D-galactosamide used is 0.02-1 wt% of the active ingredient of Atractylodes macrocephala. After using the active ingredient of Atractylodes macrocephala and the lipopeptide derivative, 2-acetamido-2-deoxy-D-galactosamide can be further added. With the use of the active ingredient of Atractylodes macrocephala and the lipopeptide derivative, the further compounding of 2-acetamido-2-deoxy-D-galactosamide has a better effect.

[0043] This invention discloses the use of a preparation of Atractylodes macrocephala in the preparation of a drug for preventing and treating neuropathy caused by tumor drugs.

[0044] This invention involves washing and drying the rhizomes of Atractylodes macrocephala to produce powder, which is then subjected to reflux extraction with water, reflux extraction with an alcohol solution, and steam distillation with water to obtain aqueous, alcoholic, and steam-distilled extracts of Atractylodes macrocephala. These extracts are then mixed to prepare a preparation of Atractylodes macrocephala. This invention can also incorporate excipients to compound the active ingredients of Atractylodes macrocephala. Excipients can include microbial lipopeptides, lipopeptide derivatives, and medical solvents. Therefore, it has the following beneficial effects: it can increase blood vessel diameter, increase blood velocity, increase vascular pulsatility index, reduce peripheral blood inflammatory factors, prevent and treat peripheral nerve damage caused by anti-tumor drugs, promote the repair of peripheral nerve apoptosis induced by anti-tumor drugs, promote the expression level of neurotrophic factors in nerve cells, and promote the repair and regeneration of nerve tissue. Therefore, this invention is a preparation of Atractylodes macrocephala that increases blood vessel diameter, increases blood velocity, increases vascular pulsatility index, reduces peripheral blood inflammatory factors, prevents and treats peripheral nerve damage caused by anti-tumor drugs, promotes the repair of peripheral nerve apoptosis induced by anti-tumor drugs, promotes the expression level of neurotrophic factors in nerve cells, and promotes the repair and regeneration of nerve tissue, as well as its uses. Attached Figure Description

[0045] Figure 1This is a wavelength scan of microbial lipopeptides.

[0046] Figure 2 This is a graph showing the rate of decrease in peripheral blood inflammatory factors. Detailed Implementation

[0047] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0048] The concepts involved in this application will first be described with reference to the accompanying drawings. It should be noted that the following descriptions of various concepts are only for the purpose of making the content of this application easier to understand and do not constitute a limitation on the scope of protection of this application; furthermore, the embodiments and features in the embodiments of this application can be combined with each other unless otherwise specified. This application will now be described in detail with reference to the accompanying drawings and embodiments.

[0049] The research basis and results of this invention: From January to December 2024, 100 female breast cancer patients with CIPN induced by taxane-based chemotherapy were recruited from the Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine. Random numbers were generated using SPASS 26.0 software. The random numbers and group assignments were placed in opaque envelopes and sealed, with the serial number affixed to the outside of the envelope. Envelopes with corresponding serial numbers were selected according to the patients' order of visit, and patients were randomly assigned in a 1:1 ratio to either the Atractylodes macrocephala group or the Western medicine group, with 50 patients in each group. During the study, treatment and assessment personnel were separated; that is, the assessment personnel were unaware of the patients' grouping and treatment details, and data analysis was conducted by a third party.

[0050] Diagnostic criteria The diagnostic criteria for breast cancer are based on "Diagnosis and Treatment of Breast Diseases" and "Comprehensive Treatment of Breast Cancer". The CIPN assessment and grading are based on the National Cancer Institute-common terminology criteria for adverse events Version 5.0 (NCI-CTCAE V5.0).

[0051] Inclusion criteria ① Female breast cancer patients aged 18 to 75 years; ② Developing grade I or higher CIPN symptoms due to the use of taxane chemotherapy drugs (including paclitaxel, albumin-bound paclitaxel, docetaxel liposomes, etc.); ③ Possessing daily living abilities, with a Karnofsky Performance Status (KPS) score >60, and able to independently complete all treatments; ④ No serious heart, liver, brain, kidney, or other organ diseases, and no serious mental illness; ⑤ Not using analgesics within 2 weeks prior to enrollment; ⑥ Voluntarily participating in this study and signing an informed consent form.

[0052] Exclusion criteria ① CIPN caused by non-taxane chemotherapy drugs; ② Pregnant women, or those with other serious diseases, end-stage cachexia, etc.; ③ CIPN caused by other diseases, such as diabetic peripheral neuropathy; ④ Those who do not cooperate with treatment or are participating in other acupuncture or drug clinical trials.

[0053] Removal and shedding criteria ① Patients were mistakenly included because they did not meet the inclusion criteria; ② Patients with poor compliance, or who could not tolerate drug treatment, or who were allergic to Atractylodes macrocephala-related components, were unable to complete the treatment and follow-up as required, and withdrew on their own.

[0054] Criteria for Termination Those whose condition progresses or develops serious complications during the study process, and who are deemed unsuitable to continue treatment after evaluation.

[0055] Treatment Western medicine group The patient was given 0.5 mg of mecobalamin tablets (Eisai China Pharmaceutical Co., Ltd., National Drug Approval Number H20143107, 0.5 mg) orally, three times a day, for four consecutive weeks.

[0056] Traditional Chinese Medicine Group Take 15g of Atractylodes macrocephala preparation, apply it to the limbs and massage for 15 minutes every morning and before going to bed, twice a day, for 4 consecutive weeks.

[0057] The preparation of Atractylodes macrocephala preparations is as follows: Atractylodes macrocephala rhizomes are washed, dried, and crushed to 30 mesh to obtain Atractylodes macrocephala powder. During the drying process, the Atractylodes macrocephala rhizomes are dried until the moisture content is below 8%. The Atractylodes macrocephala powder is mixed with pure water and extracted by reflux at 100℃ for 4 hours. The residue is removed by filtration, and the mixture is concentrated to 20 vol% at 40℃. Ethanol is added, and the mixture is allowed to stand to precipitate polysaccharides. The supernatant is collected by centrifugation to obtain the Atractylodes macrocephala water extract. The amount of Atractylodes macrocephala powder used is 10 wt% of pure water. The amount of ethanol used is 500 wt% of pure water. The Atractylodes macrocephala powder is mixed with the ethanol solution and extracted by reflux at 70℃ for 4 hours. The residue is removed by filtration, and the ethanol is concentrated to recover the extract, yielding the Atractylodes macrocephala alcohol extract. The ethanol solution is a mixture of ethanol and water, with an ethanol content of 70 wt%. The amount of Atractylodes macrocephala powder used is 12.5 wt% of the ethanol solution. The Atractylodes macrocephala powder is mixed with pure water and steam distilled for 4 hours. The volatile oil is collected by oil-water separation and dehydrated with anhydrous sodium sulfate to obtain the Atractylodes macrocephala water distillation product. The amount of Atractylodes macrocephala powder used is 20 wt% of pure water; the water extract, alcohol extract and steamed product of Atractylodes macrocephala are mixed in a volume ratio of 1:1:1 to obtain the Atractylodes macrocephala preparation.

[0058] Therapeutic effect observation Observation indicators The following indicators were assessed during follow-up visits before treatment, after treatment, and 4 weeks after the completion of all treatments. Key outcome indicators The Functional Assessment of Cancer Therapy / Gynaecologic Oncology Group-Neurotoxicity (FACT / GOG-Ntx) scoring system consists of 11 items: 4 sensory items, 2 auditory items, 3 motor items, and 2 functional impairment items. It demonstrates good reliability and validity in the Chinese cancer population. Each item is scored from mild to severe as 0, 1, 2, 3, and 4 points, with a total score ranging from 0 to 44 points. Higher scores indicate more severe neuropathy. Secondary outcome indicators (1) Peripheral neurotoxicity grading of the National Cancer Institute (NCI-CTCAE V5.0): Chemotherapy-induced peripheral neuropathy is classified into four grades from mild to severe, which is the standard scale for grading the severity of CIPN. Grade I: Loss of tendon reflexes or numbness (including pinprick), but without affecting function; Grade II: Loss of sensation or numbness (including pinprick), affecting function but not affecting daily living activities; Grade III: Loss of sensation or numbness (including pinprick), affecting daily living activities; Grade IV: Sensorimotor neuropathy, significantly interfering with daily living activities. In addition to the above four grades, in this study, grade 0 indicates that the patient has no CIPN symptoms or has completely recovered from CIPN. (2) Visual analogue scale (VAS) score for peripheral nerve pain: VAS was used to assess peripheral nerve pain caused by chemotherapy drugs at each time point. The total score ranged from 0 to 10 points, with 0 points indicating no pain, 1 to 3 points indicating mild pain, 4 to 6 points indicating moderate pain, and 7 to 10 points indicating severe pain. (3) The European Organisation for the Study and Treatment of Cancer Patients’ Quality of Life (EORTCQLQ-CIPN 20) scores patients’ quality of life. The assessment scale mainly includes three aspects: sensory nerves, motor nerves and autonomic nerves, with a total of 20 items. The description of the condition is divided into four levels from mild to severe, with a total score of 20 to 80 points.

[0059] (4) ECOG score: The ECOG score is divided into 6 levels from 0 to 5 based on the patient's activity level. A score of 0 represents that the patient's activity level is completely normal, and a score of 5 represents that the patient is dead. The higher the score, the worse the quality of life.

[0060] (5) Safety evaluation: Observe and record various adverse events such as allergies and subcutaneous hematomas that occur during the study, record the treatment process, and evaluate whether the patient can continue to participate in this study.

[0061] (6) Efficacy evaluation criteria: Based on clinical practice experience, self-formulated efficacy evaluation criteria were used to evaluate clinical efficacy after treatment. Significant effect: FACT / GOG-Ntx score decreased by ≥6 points compared to before treatment; Effective: FACT / GOG-Ntx score decreased by 3 to <6 points compared to before treatment; Ineffective: FACT / GOG-Ntx score decreased by <3 points or worsened. Mechanism Indicators (1) Doppler ultrasound examination of the limb blood vessels: Before and after treatment, the arteries of the lower limbs were examined using a color Doppler ultrasound diagnostic instrument. The dorsalis pedis artery was examined about 3 cm distal to the affected ankle joint, and the blood vessel diameter, blood flow velocity and pulsatility index were recorded.

[0062] (2) Peripheral blood inflammatory factors: The levels of peripheral blood inflammatory factors interleukin-1 and interleukin-6 were measured before treatment.

[0063] Statistical processing SPSS 23.0 software was used for statistical analysis of the data. All data were first subjected to a normality test, with different test methods applied depending on whether the data were normally distributed. Normally distributed continuous data were expressed as mean ± standard deviation (x ± s), while non-normally distributed data were expressed as median and interquartile range. The independent samples t-test was used for between-group comparisons of two groups of count data, and the paired samples t-test was used for within-group comparisons of two groups of count data. For non-normally distributed continuous data, the median and interquartile range were used to express the level of change, and the Mann-Whitney U test was used for between-group comparisons of non-normally distributed data. The chi-square test was used for count data.

[0064] Research Results This study included 100 patients, all of whom completed treatment-related studies. There were no statistically significant differences among the groups in terms of age, disease duration, body mass index (BMI), KPS score, number of chemotherapy sessions and regimens, and whether the tumor had metastasized (P > 0.05), indicating comparability (see Table 1).

[0065] Table 1. Data on peripheral neuropathy induced by taxane chemotherapy in female breast cancer patients in each group.

[0066] Table 2 shows the comparison of FACT / GOG-Ntx scores, VAS scores, EORTC QLQ-CIPN 20 scores, and ECOG scores of patients in each group before and after treatment at each time point.

[0067] Before treatment, there were no statistically significant differences in FACT / GOG-Ntx scores, VAS scores, EORTC QLQ-CIPN 20 scores, and ECOG scores among the different groups (P > 0.05), indicating comparability. After treatment, the FACT / GOG-Ntx and EORTC QLQ-CIPN 20 scores significantly decreased in both groups (P < 0.05), while there were no significant differences in VAS and ECOG scores (P > 0.05). Compared with the Western medicine group, the reduction in FACT / GOG-Ntx and EORTC QLQ-CIPN 20 scores was more significant in the traditional Chinese medicine group (P < 0.05).

[0068] Table 2. Scores of patients in each group before and after treatment

[0069] Note: Compared with the pre-treatment values ​​in this group, *P<0.05; compared with the control group at the same time point, #P<0.05; Table 3 shows the comparison of limb blood flow and peripheral blood inflammatory factors at different time points before and after treatment in each group of patients.

[0070] Before treatment, there were no statistically significant differences in the vascular conditions (vascular diameter, blood flow velocity, pulsatility index) and peripheral blood inflammatory factors (IL-6, IL-1) between the two groups (P > 0.05), indicating comparability. After treatment, both groups showed significant improvement in the vascular conditions (vascular diameter, blood flow velocity, pulsatility index) and peripheral blood inflammatory factors (IL-6, IL-1) (P < 0.05). Compared with the Western medicine group, the improvement in the vascular conditions (vascular diameter, blood flow velocity, pulsatility index) and peripheral blood inflammatory factors (IL-6, IL-1) of the lower extremities was more significant in the traditional Chinese medicine group (P < 0.05).

[0071] Table 3. Comparison of limb blood flow and peripheral blood inflammatory factors at different time points before and after treatment in each group of patients.

[0072] Note: Compared with the pre-treatment values ​​in this group, *P<0.05; compared with the control group at the same time point, #P<0.05; The effective rates of each group of patients after treatment are shown in Table 4.

[0073] After treatment, the overall effective rate of the traditional Chinese medicine group was 88.0%, which was significantly higher than that of the Western medicine group (70.0%) (P<0.05).

[0074] Table 4. Effective rate results of each group of patients after treatment

[0075] Compared with the control group at the same time, #P<0.05.

[0076] Example 1: A method for preparing a preparation of Atractylodes macrocephala. Preparation of Atractylodes macrocephala powder: The rhizomes of Atractylodes macrocephala were washed, dried, and then crushed to 30 mesh using a pulverizer to obtain Atractylodes macrocephala powder. During the drying process, the rhizomes of Atractylodes macrocephala were dried until the moisture content was below 8%.

[0077] Preparation of Atractylodes macrocephala water extract: Atractylodes macrocephala powder was mixed with pure water and extracted by reflux at 100℃ for 4 hours. The residue was removed by filtration, and the mixture was concentrated to 20 vol% at 40℃. Ethanol was added and allowed to stand to precipitate the polysaccharides. The supernatant was collected by centrifugation to obtain the Atractylodes macrocephala water extract. The amount of Atractylodes macrocephala powder used was 10 wt% of pure water. The amount of ethanol used was 500 wt% of pure water.

[0078] Preparation of Atractylodes macrocephala ethanol extract: Atractylodes macrocephala powder was mixed with an ethanol solution and extracted by reflux at 70℃ for 4 hours. The residue was removed by filtration, and the ethanol was concentrated and recovered to obtain the extract. The ethanol solution was a mixture of ethanol and water, with an ethanol content of 70 wt%. The amount of Atractylodes macrocephala powder used was 12.5 wt% of the ethanol solution.

[0079] Preparation of Atractylodes macrocephala hydrosol product: Atractylodes macrocephala powder was mixed with pure water and steam distilled for 4 hours. The volatile oil was collected after oil-water separation and dehydrated with anhydrous sodium sulfate to obtain the Atractylodes macrocephala hydrosol product. The amount of Atractylodes macrocephala powder used was 20 wt% of pure water.

[0080] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed to obtain the preparations. The active ingredients of Atractylodes macrocephala include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala water-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala water-distilled product used is 100 vol% of the Atractylodes macrocephala water extract.

[0081] Example 2: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 1 lies in the preparation of the Atractylodes macrocephala preparation. Microbial lipopeptides were added during the preparation of the Atractylodes macrocephala preparation.

[0082] Preparation of microbial lipopeptides: Bacillus licheniformis strain was inoculated into fermentation medium at a volume fraction of 1% and cultured for 5 days. The bacterial cells and supernatant were separated by centrifugation. The bacterial cells were then disrupted to obtain a lysate. The supernatant and lysate were mixed and extracted using an extractant. The organic phase was separated, distilled under reduced pressure, and freeze-dried to obtain the microbial lipopeptides. The fermentation medium contained 20 g / L corn steep liquor, 20 g / L glucose, 3 g / L sodium gluconate, 2 g / L yeast extract, 2 g / L ammonium sulfate, 2 g / L disodium hydrogen phosphate, 2 g / L dipotassium hydrogen phosphate, 2 g / L calcium chloride, 1 g / L calcium carbonate, 0.5 g / L magnesium sulfate, 0.5 g / L potassium chloride, and 0.03 g / L ferric chloride. The pH was adjusted to neutral, with the remainder being water. The bacterial cells were disrupted using an ultrasonic disruptor at 25℃ and a frequency of 25 kHz. Dichloromethane was used as the extractant. The preservation number of Bacillus licheniformis is CGMCC No. 5686.

[0083] The present invention performed wavelength scanning on the microbial lipopeptides prepared above, and the results are as follows: Figure 1 As shown.

[0084] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-distilled product used is 100 vol%. The excipients include microbial lipopeptides, which are used at 1.2 wt% of the active ingredients of Atractylodes macrocephala.

[0085] Example 3: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 2 lies in the preparation of the Atractylodes macrocephala preparation. A lipopeptide derivative was added during the preparation of the Atractylodes macrocephala preparation.

[0086] Preparation of lipopeptide derivatives: The derivatizing agent was mixed with deionized water, the pH was adjusted to 5, and an EDC / NHSS solution was added and stirred. The mixture was treated at 40℃ for 30 min, then microbial lipopeptides were added, and the reaction was carried out at 40℃ for 4 h. After the reaction was completed, EDC and NHSS were removed by ultrafiltration, and the lipopeptide derivatives were obtained by freeze drying. The derivatizing agent included D-glucosamine and N,N-dimethylglycine. The amount of D-glucosamine used was 0.1 wt% of deionized water, the amount of N,N-dimethylglycine used was 60 wt% of D-glucosamine, the amount of EDC used was 30 wt% of D-glucosamine, the amount of NHSS used was 30 wt% of D-glucosamine, and the amount of microbial lipopeptides used was 700 wt% of D-glucosamine.

[0087] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-distilled product used is 100 vol%. The excipients include lipopeptide derivatives, and the amount of lipopeptide derivatives used is 1.2 wt% of the active ingredients of Atractylodes macrocephala.

[0088] Example 4: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the lipopeptide derivative.

[0089] Preparation of lipopeptide derivatives: The derivatizing agent was mixed with deionized water, the pH was adjusted to 5, and an EDC / NHSS solution was added and stirred. The mixture was treated at 40℃ for 30 min, then microbial lipopeptides were added, and the reaction was carried out at 40℃ for 4 h. After the reaction was completed, EDC and NHSS were removed by ultrafiltration, and the lipopeptide derivatives were obtained by freeze drying. The derivatizing agent included D-glucosamine and N,N-dimethylglycine. The amount of D-glucosamine used was 0.2 wt% of deionized water, the amount of N,N-dimethylglycine used was 80 wt% of D-glucosamine, the amount of EDC used was 30 wt% of D-glucosamine, the amount of NHSS used was 30 wt% of D-glucosamine, and the amount of microbial lipopeptides used was 700 wt% of D-glucosamine.

[0090] Example 5: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the Atractylodes macrocephala preparation.

[0091] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-distilled product used is 100 vol%. The excipients include lipopeptide derivatives, which are used at 3.9 wt% of the active ingredients of Atractylodes macrocephala.

[0092] Example 6: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the Atractylodes macrocephala preparation. 2-acetamido-2-deoxy-D-galactosamide was added during the preparation of the Atractylodes macrocephala preparation.

[0093] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-dried product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-dried product used is 100 vol%. The excipients include lipopeptide derivatives and 2-acetamido-2-deoxy-D-galactosamide. The amount of lipopeptide derivative used is 1.2 wt% of the active ingredients of Atractylodes macrocephala, and the amount of 2-acetamido-2-deoxy-D-galactosamide used is 0.3 wt% of the active ingredients of Atractylodes macrocephala.

[0094] Example 7: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the Atractylodes macrocephala preparation. 2-acetamido-2-deoxy-D-galactosamide was added during the preparation of the Atractylodes macrocephala preparation.

[0095] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-distilled product used is 100 vol%. The excipients include lipopeptide derivatives and 2-acetamido-2-deoxy-D-galactosamide. The amount of lipopeptide derivative used is 1.2 wt% of the active ingredients of Atractylodes macrocephala, and the amount of 2-acetamido-2-deoxy-D-galactosamide used is 0.5 wt% of the active ingredients of Atractylodes macrocephala.

[0096] Example 8: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 1 lies in the preparation of the Atractylodes macrocephala preparation. Isopropanol was added during the preparation of the Atractylodes macrocephala preparation.

[0097] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-distilled product used is 100 vol% of the amount of Atractylodes macrocephala water extract. The excipients include isopropanol, which is used at 50 wt% of the amount of active ingredients of Atractylodes macrocephala.

[0098] Example 9: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 2 lies in the preparation of the Atractylodes macrocephala preparation. Isopropanol was added during the preparation of the Atractylodes macrocephala preparation.

[0099] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-distilled product used is 100 vol%. The excipients include microbial lipopeptides and isopropanol. The amount of microbial lipopeptides used is 1.2 wt% of the active ingredients of Atractylodes macrocephala, and the amount of isopropanol used is 50 wt% of the active ingredients of Atractylodes macrocephala.

[0100] Example 10: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the Atractylodes macrocephala preparation. Isopropanol was added during the preparation of the Atractylodes macrocephala preparation.

[0101] Preparation of Atractylodes macrocephala preparations: The active ingredients of Atractylodes macrocephala are mixed with excipients to obtain the preparations. The active ingredients include Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam-distilled product. The amount of Atractylodes macrocephala alcohol extract used is 100 vol% of the amount of Atractylodes macrocephala water extract, and the amount of Atractylodes macrocephala steam-distilled product used is 100 vol%. The excipients include lipopeptide derivatives and isopropanol. The amount of microbial lipopeptide used is 1.2 wt% of the active ingredients of Atractylodes macrocephala, and the amount of isopropanol used is 50 wt% of the active ingredients of Atractylodes macrocephala.

[0102] Comparative Example 1: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the lipopeptide derivative. D-glucosamine was not added in the preparation of the lipopeptide derivative; other reagents and amounts were the same as those in Example 3.

[0103] Comparative Example 2: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the lipopeptide derivative. N,N-dimethylglycine was not added in the preparation of the lipopeptide derivative; other reagents and amounts were the same as those in Example 3.

[0104] Comparative Example 3: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 3 lies in the preparation of the lipopeptide derivative. In the preparation of the lipopeptide derivative, the amount of D-glucosamine used is 0.1 wt% of deionized water, the amount of N,N-dimethylglycine used is 60 wt% of D-glucosamine, and the other reagents and amounts are the same as those in Example 3.

[0105] Comparative Example 4: A method for preparing a preparation of Atractylodes macrocephala. The difference between this embodiment and Example 6 lies in the preparation of the Atractylodes macrocephala preparation. No lipopeptide derivatives were added in the preparation of the Atractylodes macrocephala preparation; other reagents and their amounts are the same as those in Example 6.

[0106] Experimental example: The expression levels of peripheral blood inflammatory factor IL-1 were tested using samples prepared in Examples 1-10 and Comparative Examples 1-4 according to the research method. The expression levels of peripheral blood inflammatory factor IL-1 without using samples were used as a control. The decrease rate of peripheral blood inflammatory factors was obtained as follows: Figure 2As shown, S1 is Example 1, S2 is Example 2, S3 is Example 3, S4 is Example 4, S5 is Example 5, S6 is Example 6, S7 is Example 7, S8 is Example 8, S9 is Example 9, S10 is Example 10, D1 is Comparative Example 1, D2 is Comparative Example 2, D3 is Comparative Example 3, and D4 is Comparative Example 4. In this invention, after washing and drying the rhizomes of Atractylodes macrocephala, Atractylodes macrocephala powder is prepared. Then, it is subjected to reflux extraction with water, reflux extraction with alcohol solution, and steam distillation with water to obtain Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala steam distillation product. These are mixed to prepare Atractylodes macrocephala preparation. In cell experiments, it can increase the IL-1 reduction rate in cells, indicating that the present invention... Atractylodes macrocephala preparations can reduce IL-1 expression in cells. This invention can also add excipients to the active ingredients of Atractylodes macrocephala. Adding microbial lipopeptides prepared from Bacillus licheniformis can increase the rate of IL-1 reduction in cells, but the effect is relatively low. In this invention, after derivatizing the microbial lipopeptides with D-glucosamine and N,N-dimethylglycine, the resulting lipopeptide derivatives, at the same dosage, show significantly better effects than the microbial lipopeptides. In the preparation of the lipopeptide derivatives, increasing the dosage of D-glucosamine and N,N-dimethylglycine can further improve the effect of the Atractylodes macrocephala preparations. Increasing the dosage of the lipopeptide derivatives during the preparation of Atractylodes macrocephala preparations can also improve the effect. This invention can also use 2-acetamido-2-deoxy-D-galactosamide in combination with the above-mentioned lipopeptide derivatives in Atractylodes macrocephala preparations, which can further increase the rate of IL-1 reduction in cells, indicating that the combined application of 2-acetamido-2-deoxy-D-galactosamide and lipopeptide derivatives in Atractylodes macrocephala preparations can reduce IL-1 expression in cells. In this invention, medical solvents such as isopropanol can also be added. The use of medical solvents cannot increase the rate of IL-1 reduction in cells, that is, medical solvents will not change the expression of IL-1 in cells.

[0107] The embodiments and / or implementation methods described above are merely preferred embodiments and / or implementation methods for implementing the technology of the present invention, and are not intended to limit the implementation methods of the technology of the present invention in any way. Any person skilled in the art can make some modifications or alterations to other equivalent embodiments without departing from the scope of the technical means disclosed in the content of the present invention, but they should still be regarded as the technology or embodiments that are substantially the same as the present invention.

[0108] This document uses specific examples to illustrate the principles and implementation methods of this application. The descriptions of the above embodiments are only for the purpose of helping to understand the methods and core ideas of this application. The above descriptions are only preferred embodiments of this application. It should be noted that due to the limitations of written expression, while there are objectively infinite specific structures, those skilled in the art can make several improvements, modifications, or changes without departing from the principles of this application, and can also combine the above technical features in an appropriate manner. These improvements, modifications, changes, or combinations, or the direct application of the inventive concept and technical solution to other situations without modification, should all be considered within the scope of protection of this application.

Claims

1. A preparation of Atractylodes macrocephala, comprising: The active ingredient and excipients of Atractylodes macrocephala are used, with the amount of excipients being 0.01-150 wt% of the active ingredient.

2. The Atractylodes macrocephala preparation according to claim 1, characterized in that: The active ingredient of Atractylodes macrocephala includes at least one of the following: Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract, and Atractylodes macrocephala water vapor extract.

3. A preparation of Atractylodes macrocephala according to claim 2, characterized in that: The active ingredients of Atractylodes macrocephala are Atractylodes macrocephala water extract, Atractylodes macrocephala alcohol extract and Atractylodes macrocephala water vapor product; The amount of Atractylodes macrocephala alcohol extract used is 50-150 vol of Atractylodes macrocephala water extract used; or, the amount of Atractylodes macrocephala steamed product used is 50-150 vol of Atractylodes macrocephala water extract used.

4. A preparation of Atractylodes macrocephala according to claim 2, characterized in that: In the preparation of the Atractylodes macrocephala water extract, Atractylodes macrocephala is mixed with water and extracted by reflux to obtain the Atractylodes macrocephala water extract. or, In the preparation of the Atractylodes macrocephala alcohol extract, Atractylodes macrocephala is mixed with an alcohol solution and extracted by reflux to obtain the Atractylodes macrocephala alcohol extract. or, In the preparation of the Atractylodes macrocephala water-distilled product, Atractylodes macrocephala is mixed with water and then steam distilled to obtain the Atractylodes macrocephala water-distilled product.

5. A preparation of Atractylodes macrocephala according to claim 1, characterized in that: The excipients include at least one of water, alcohol, ester, ether and biological agents.

6. A preparation of Atractylodes macrocephala according to claim 5, characterized in that: The alcohol agent includes at least one of methanol, ethanol, propylene glycol, isopropanol, ethylene glycol, and polyethylene glycol; or, The ether agent includes at least one selected from diethyl ether, diethylene glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol diethyl ether, ethylene glycol monobutyl ether, and ethylene glycol dibutyl ether; or, The ester agent includes at least one of polyethylene glycol laurate, propylene glycol laurate, and glyceryl caprylate; or, The biological agent includes at least one of microbial lipopeptides, lipopeptide derivatives, polypeptides, and polypeptide derivatives.

7. A preparation of Atractylodes macrocephala according to claim 5, characterized in that: The excipient is a microbial lipopeptide, which is isolated from Bacillus licheniformis through fermentation culture.

8. A preparation of Atractylodes macrocephala according to claim 5, characterized in that: The excipient is a lipopeptide derivative, which is derived from microbial lipopeptides and a derivatizing agent.

9. A preparation of Atractylodes macrocephala according to claim 1, characterized in that: The excipients include medical solvents or pharmaceutical solvents.

10. Use of any one of the Atractylodes macrocephala preparations according to claims 1-9 in the preparation of a drug for preventing and treating neuropathy caused by tumor drugs.

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