A Chinese medicine composition for preventing and treating oxaliplatin-induced peripheral neuropathic pain, and its preparation method and application

Through a composition containing a variety of traditional Chinese medicine ingredients, the treatment of peripheral neuropathic pain caused by oxaliplatin using topical methods has solved the problem of poor efficacy of existing treatment methods, and achieved significant improvement of pain symptoms and improved quality of life Effect.

CN116942783BActive Publication Date: 2025-02-11ENSHI TUJIA & MIAO AUTONOMOUS PREFECTURE CENT HOSPITAL
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Patent Information

Application Number
CN202311003094.3
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-08-10
Publication Date
2025-02-11
Estimated Expiration
2043-08-10

AI Technical Summary

Technical Problem

The peripheral neuropathic pain caused by chemotherapy drugs such as oxaliplatin, the existing treatment methods are not effective and have great side effects, and it is urgent to find safe and effective treatment methods.

Method used

Provided is a traditional Chinese medicine composition, including astragalus, cinnamon twig, white peony, geranium, angelica, reed root, orchid cypress leaves, motherwort, Qianliguang, loofah, aloe, jujube, fairy grass and su The solution diluted by external methods is subjected to constant temperature washing, which is used to prevent and treat peripheral neuropathic pain caused by oxaliplatin.

Benefits of technology

It significantly improves peripheral nerve pain caused by oxaliplatin, improves the quality of life of patients, and is simple in preparation and safe and easy to use.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention provides a Chinese medicine composition having the function of significantly improving oxaliplatin-induced peripheral neuropathic pain, and a preparation method and application thereof. The Chinese medicine composition is composed of astragalus, cinnamon twig, white peony root, geranium, flue gastrodia elata, ginger, angelica, reed root, cypress leaf, motherwort, senecio, loofah, aloe, acanthopanax bark, jujube, curculigo orchioides, and sappan wood.
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Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for preventing and treating oxaliplatin-induced peripheral neuropathic pain, and a preparation method and application thereof. Background Art

[0002] Chemotherapy-induced peripheral neuropathic pain (CIPNP) is neuropathic pain caused by chemotherapy drugs such as taxanes, platinums, and vinca alkaloids. Literature reports show that more than 60% of patients who use chemotherapy drugs will experience varying degrees of peripheral neuropathy, which is mainly manifested as hyperalgesia, burning pain, and tingling in a stocking-like distribution. Symptoms persist or worsen after drug withdrawal, which is a factor that seriously affects the quality of life of chemotherapy patients. Patients often change their treatment plans or even give up chemotherapy due to unbearable pain. The current first-line drugs for treatment are mainly antidepressants and anticonvulsants, but they only relieve symptoms, have unsatisfactory efficacy, and have large side effects. Therefore, there is an urgent need to find safe and effective treatment methods. Natural Chinese herbal medicine raw materials are easy to obtain, safe and effective, but the efficacy of oral Chinese medicine alone is not good, so the external use of Chinese medicine has more advantages. Summary of the invention

[0003] In view of the deficiencies in the prior art, the object of the present invention is to provide a Chinese medicine composition and a preparation method and application thereof, and in particular to provide a Chinese medicine composition for preventing and treating oxaliplatin-induced peripheral neuropathic pain and a preparation method and application thereof.

[0004] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0005] In the first aspect, the present invention provides a Chinese medicine composition for preventing and treating peripheral neuropathic pain caused by oxaliplatin, wherein the raw materials for preparing the Chinese medicine composition are: 1-30 parts of astragalus, 1-30 parts of cassia twig, 3-30 parts of white peony root, 3-30 parts of geranium, 3-20 parts of liquidambar formosana, 1-20 parts of ginger, 1-30 parts of angelica, 5-30 parts of reed root, 2-20 parts of oriental arborvitae, 1-15 parts of motherwort, 1-30 parts of senecio, 2-15 parts of loofah, 2-15 parts of aloe, 1-20 parts of acanthopanax bark, 1-20 parts of jujube, 3-20 parts of curculigo, and 3-20 parts of sappan wood. The various Chinese medicines involved in the present invention can be purchased from general Chinese medicine stores, and their specifications meet the standards of the Chinese Pharmacopoeia.

[0006] Preferably, the raw materials for preparing the traditional Chinese medicine composition are: 5-20 parts of astragalus, 5-20 parts of cinnamon twig, 10-20 parts of white peony root, 5-25 parts of geranium, 10-18 parts of rhizoma liquidambar formosana, 5-15 parts of ginger, 5-25 parts of angelica, 10-25 parts of reed rhizome, 5-18 parts of orientalis leaves, 3-10 parts of motherwort, 2-25 parts of senecio, 5-10 parts of luffa, 5-10 parts of aloe, 5-15 parts of acanthopanax bark, 5-15 parts of jujube, 5-18 parts of curculigo, and 5-18 parts of sappan wood.

[0007] More preferably, the raw materials for preparing the traditional Chinese medicine composition are: 20 parts of astragalus, 20 parts of cinnamon twig, 18 parts of white peony root, 20 parts of geranium, 15 parts of rhizoma liquidambar formosana, 10 parts of ginger, 22 parts of angelica, 16 parts of rhizoma reticulatae, 9 parts of orientalis leaves, 5 parts of motherwort, 20 parts of senecio, 7 parts of luffa, 6 parts of aloe, 10 parts of acanthopanax bark, 10 parts of jujube, 12 parts of curculigo, and 12 parts of sappan wood.

[0008] In a second aspect, the present invention provides a method for preparing the Chinese medicine composition, characterized in that it comprises the following steps:

[0009] S1. Weigh the Chinese medicinal materials by weight, wash and dry the above Chinese medicinal materials for later use;

[0010] S2. Take the washed and dried astragalus, cinnamon twig, white peony root, ginger, angelica, acanthopanax bark, and sappan wood, add water at a liquid-to-material ratio of 2:1-8:1, soak for 20-120 minutes, then add the remaining Chinese medicinal materials, first boil over high heat, then simmer over low heat for 0.5-3 hours, filter and concentrate to obtain the Chinese medicine composition.

[0011] Furthermore, the liquid-to-solid ratio is 5:1, the soaking time is 45 minutes, and the decoction time is 2.5 hours.

[0012] In a third aspect, the present invention provides a method for using the Chinese medicine composition in preventing and treating oxaliplatin-induced peripheral neuropathic pain, specifically: the method of use is external use, after diluting the prepared medicine solution, soaking and washing the patient's limbs at a constant temperature.

[0013] In a fourth aspect, the present invention provides a use of the traditional Chinese medicine composition in the preparation of a drug for preventing and treating oxaliplatin-induced peripheral neuropathic pain.

[0014] Among them, Astragalus memeranaceus (Fisch.) Bge. Var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. of the genus Astragalus in the Leguminosae family has the effects of strengthening the spleen and replenishing the middle, raising yang and lifting the sunken, strengthening the body's defense system, promoting urination, and removing toxins and promoting muscle growth. It is mainly used to treat spleen qi deficiency syndrome, lung qi deficiency syndrome, qi deficiency and spontaneous sweating syndrome, qi and blood deficiency, sores that are difficult to heal or ulcers that are difficult to heal, or sores that are difficult to heal after a long time.

[0015] Among them, cinnamon twig is the tender branch of Cinnamomum cassia Presl., a plant of Lauraceae. It has the effects of sweating and relieving muscles, warming and unblocking meridians, promoting yang and transforming qi, and balancing and descending qi. It is often used for colds, cold pain in the abdomen, amenorrhea due to cold blood, joint pain, phlegm and fluid retention, edema, palpitations, etc.

[0016] White peony root is the dried root of Paeonia lactiflora Pall., a plant of the Ranunculaceae family. It has the effects of nourishing blood and regulating menstruation, restraining yin and stopping sweating, softening the liver and relieving pain, and calming liver yang. It is often used for blood deficiency and chlorosis, irregular menstruation, spontaneous sweating, night sweats, flank pain, abdominal pain, cramps in the limbs, headache and dizziness.

[0017] Among them, geranium is the whole herb with fruits of the plants of Geranium family, including Erodium stephanianum Willd., Geranium wilfordii Maxim., Geranium sibiricum L., Geranium nepalense Sweet, Geranium dahuricum DC. It has the effects of dispelling wind and dredging collaterals, activating blood circulation, clearing away heat and removing dampness. It is often used for rheumatic arthralgia, numbness of the skin, soreness of tendons and bones, injuries from falls, diarrhea, dysentery, and sores.

[0018] Among them, Liquidambar formosana Hance is the dried mature infructescence of Liquidambar formosana Hance, a plant of the Hamamelidaceae family. It has the effects of dispelling wind and activating collaterals, promoting diuresis, and regulating menstruation. It is often used for joint pain, numbness and spasm, edema, insufficient milk, and amenorrhea.

[0019] Among them, ginger is the fresh rhizome of the perennial herb ginger of the ginger family. Ginger tastes spicy and is slightly warm in nature. It enters the lung, spleen, and stomach meridians. It has the effects of dispelling cold, warming the middle and stopping vomiting, warming the lungs and stopping coughs, and detoxifying. It is often used for colds caused by wind and cold, cold spleen and stomach syndrome, vomiting caused by stomach cold, cough caused by lung cold, and detoxification of fish and crabs.

[0020] Among them, Angelica sinensis is the dried root of Angelica sinensis (Oliv.) Diels, a plant of the Umbelliferae family. It has the effects of nourishing blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and relieving constipation. It is often used for blood deficiency and sallow complexion, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, injuries from falls, carbuncles, ulcers, and constipation caused by dry intestines. Wine Angelica sinensis promotes blood circulation and regulates menstruation. It is used for amenorrhea and dysmenorrhea, rheumatic arthralgia, and injuries from falls.

[0021] Among them, reed root is the fresh or dried rhizome of the monocotyledonous plant Phragmites australis. It has the effects of clearing away heat and promoting body fluid, relieving restlessness, stopping vomiting, and promoting diuresis. It is often used for fever and thirst in febrile diseases, vomiting due to stomach heat, cough due to lung heat, and thick and yellow phlegm.

[0022] Among them, Platycladus orientalis leaves are the dried branches and leaves of Platycladus orientalis (L.) Franco, a plant of the Cupressaceae family. It has the effects of cooling blood and stopping bleeding, promoting hair growth and darkening hair. It is often used for vomiting blood, epistaxis, hemoptysis, blood in the stool, metrorrhagia, blood heat and hair loss, and premature graying of hair.

[0023] Among them, motherwort is the fresh or dried aerial part of the Labiatae plant Leonurus japonicus Houtt. It has the effects of promoting blood circulation and regulating menstruation, promoting diuresis and reducing swelling, clearing away heat and detoxifying. It is used for irregular menstruation, dysmenorrhea, amenorrhea, lochia retention, edema, oliguria, sores and swelling.

[0024] Among them, Senecio scandens Buch.-Ham. is a plant of the genus Senecio in the Asteraceae family. The whole plant is used as medicine. It has the effects of clearing away heat and detoxifying, cooling blood and reducing swelling, clearing the liver and improving eyesight, killing insects and relieving itching. It is often used for wind-fire red eyes, sores, boils, swelling, skin eczema, dysentery and abdominal pain.

[0025] Among them, loofah is the vascular bundle of the dried mature fruit of Luffa cylindrica (L.) Roem., a plant of the Cucurbitaceae family. It has the effects of dispelling wind, unblocking meridians, activating blood circulation, and promoting lactation. It is often used to treat arthralgia, cramps, chest and flank pain, milk obstruction, and mastitis.

[0026] Among them, aloe vera is a concentrated dry product of leaf juice of Aloe vera L., Aloe vera L. var. chinensis (Haw.) Berger., and Aloe ferox Mill. of the Liliaceae family. It has the effects of purgation, liver cleansing, and insecticide. It is often used for constipation due to heat accumulation, headache due to liver fire, conjunctivitis, abdominal pain due to worm accumulation, scabies, and hemorrhoids and fistulas.

[0027] Among them, Acanthopanax bark is the dried root bark of Acanthopanar gracilistμlus W.W.Smith, a plant of the Araliaceae family. It has the effects of removing rheumatism, nourishing the liver and kidneys, strengthening tendons and bones, and promoting diuresis and reducing swelling. It is often used for rheumatic arthritis, weakness of tendons and bones, delayed walking in children, physical weakness, edema, and beriberi.

[0028] Among them, jujube is the mature fruit of the plant jujube of the Rhamnaceae family. Functions and indications: tonifying the spleen and stomach, replenishing qi and promoting body fluid, regulating the Ying and Wei, and detoxifying drugs. It can treat weak stomach, poor appetite, weak spleen, loose stools, insufficient qi, blood and body fluids, disharmony between Ying and Wei, palpitations, and impotence in women.

[0029] Among them, Curculigo is the dried rhizome of Curculigo orchioides Gaertn. of the Amaryllis family. It has the effects of tonifying kidney yang, strengthening tendons and bones, and removing cold and dampness. It is often used for impotence, cold sperm, weak tendons and bones, cold numbness of the waist and knees, and cold diarrhea due to yang deficiency.

[0030] Among them, the wood of Caesalpinia sappan L., a tree of the Leguminosae family, has the effects of removing blood stasis, promoting menstruation, and healing wounds. It is often used for blood stasis, amenorrhea, postpartum blood stasis and pain, and pain caused by falls.

[0031] The beneficial effects of the present invention are:

[0032] In the Chinese medicine composition involved in the present invention, astragalus, cinnamon twig, geranium, and angelica are the main drugs, which warm the meridians and dredge the meridians, and nourish the blood; white peony root, fennel, and cauliflower are the ministerial drugs, which dispel wind and activate the collaterals, cool blood and reduce swelling; Phragmites australis, Platycladus orientalis, Acanthopanax cortex, jujube, and Sappan wood are the adjuvant drugs, which cool blood and stop bleeding, tonify the kidney and strengthen the tendons, and reduce swelling and relieve pain; Leonurus japonicus, luffa, aloe, curculigo, and ginger are the guiding drugs, which dispel cold and dredge the meridians, and warm the middle and relieve the exterior. All the drugs are used together to achieve the effects of warming the meridians and dredge the meridians, cooling blood and activating blood circulation, and dispelling cold and relieving pain. The seventeen kinds of Chinese medicine ingredients complement each other and synergize with each other, and have very significant effects in preventing and treating peripheral neuropathic pain caused by oxaliplatin, and can significantly improve the quality of life of patients, and the preparation method is simple, safe and convenient to use, and is an effective Chinese medicine prescription for preventing and treating peripheral neuropathic pain caused by oxaliplatin. DETAILED DESCRIPTION

[0033] In order to better understand the present invention, the embodiments of the present invention are described in detail below in conjunction with examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention.

[0034] Embodiment 1:

[0035] A traditional Chinese medicine composition for preventing and treating oxaliplatin-induced peripheral neuropathic pain, comprising the following raw materials: 1-30 parts of astragalus, 1-30 parts of cassia twig, 3-30 parts of white peony root, 3-30 parts of geranium, 3-20 parts of liquidambar formosana, 1-20 parts of ginger, 1-30 parts of angelica, 5-30 parts of reed root, 2-20 parts of oriental arborvitae leaves, 1-15 parts of motherwort, 1-30 parts of senecio, 2-15 parts of luffa, 2-15 parts of aloe, 1-20 parts of acanthopanax cortex, 1-20 parts of jujube, 3-20 parts of curculigo and 3-20 parts of sappan wood.

[0036] A method for preparing the Chinese medicine composition comprises the following steps:

[0037] S1. Weigh the Chinese medicinal materials by weight, wash and dry the above Chinese medicinal materials for later use;

[0038] S2. Take the washed and dried astragalus, cinnamon twig, white peony root, ginger, angelica, and acanthopanax bark, add water at a liquid-to-material ratio of 3:1, soak for 30 minutes, then add the remaining Chinese medicinal materials, boil over high heat first, then simmer over low heat for 1.5 hours, filter and concentrate to 200 ml to obtain the Chinese medicine composition.

[0039] Embodiment 2:

[0040] A traditional Chinese medicine composition for preventing and treating oxaliplatin-induced peripheral neuropathic pain, comprising the following raw materials: 5-20 parts of astragalus, 5-20 parts of cassia twig, 10-20 parts of white peony root, 5-25 parts of geranium, 10-18 parts of liquidambar formosana, 5-15 parts of ginger, 5-25 parts of angelica, 10-25 parts of reed rhizome, 5-18 parts of oriental arborvitae leaves, 3-10 parts of motherwort, 2-25 parts of senecio, 5-10 parts of luffa, 5-10 parts of aloe, 5-15 parts of acanthopanax cortex, 5-15 parts of jujube, 5-18 parts of curculigo and 5-18 parts of sappan wood.

[0041] S1. Weigh the Chinese medicinal materials by weight, wash and dry the above Chinese medicinal materials for later use;

[0042] S2. Take the washed and dried astragalus, cinnamon twig, white peony root, ginger, angelica, and acanthopanax bark, add water at a liquid-to-material ratio of 8:1, soak for 120 minutes, then add the remaining Chinese medicinal materials, boil over high heat first, then simmer over low heat for 3 hours, filter and concentrate to 200 ml to obtain the Chinese medicine composition.

[0043] Embodiment 3:

[0044] A traditional Chinese medicine composition for preventing and treating oxaliplatin-induced peripheral neuropathic pain, comprising the following raw materials: 20 parts of astragalus, 20 parts of cassia twig, 18 parts of white peony root, 20 parts of geranium, 15 parts of rhizoma liquidambar formosana, 10 parts of ginger, 22 parts of angelica, 16 parts of rhizoma reticulatae, 9 parts of orientalis leaves, 5 parts of motherwort, 20 parts of senecio radix, 7 parts of luffa, 6 parts of aloe, 10 parts of acanthopanax cortex, 10 parts of jujube, 12 parts of curculigo and 12 parts of sappan wood.

[0045] A method for preparing the Chinese medicine composition comprises the following steps:

[0046] S1. Weigh the Chinese medicinal materials by weight, wash and dry the above Chinese medicinal materials for later use;

[0047] S2. Take the washed and dried astragalus, cinnamon twig, white peony root, ginger, angelica, and acanthopanax bark, add water at a liquid-to-material ratio of 5:1, soak for 45 minutes, then add the remaining Chinese medicinal materials, boil them over high heat, then simmer over low heat for 2.5 hours, filter and concentrate to 200 ml to obtain the Chinese medicine composition.

[0048] Embodiment 4:

[0049] The model of peripheral neuropathic pain induced by oxaliplatin was established by intraperitoneal injection of oxaliplatin. The establishment method of the model was specifically improved by the method described in the reference (Holmes J, Stanko J, Varchenko M, et al. Comparative Neurotoxicity of Oxaliplatin, Cisplatin, and Ormaplatin in a Wistar Rat Model [J]. Toxicological Sciences, 1998, 46 (2): 342-351.), and 30 SD rats were divided into a control group, a model group, and a treatment group, with 10 rats in each group. Except for the control group, rats in the other groups were intraperitoneally injected with 4 mg / kg of oxaliplatin on the 1st, 3rd, 5th, 7th, 10th, and 14th days of the experiment. After the 14th day of the experiment, a stable oxaliplatin-induced peripheral neuropathy model was established. Mechanical allodynia test and cold stimulus allergic reaction test were performed before modeling, before administration after successful modeling, and after administration. After the model was successfully established, three transparent plastic boxes with covers were taken, and the drug solution prepared in Example 3 (diluted with deionized water at room temperature to contain 100 ml / L of drug solution) was poured into one of the plastic boxes so that the four feet of the rats could be immersed in it. The same volume of deionized water at room temperature was poured into the other two plastic boxes, and the three groups of rats were placed in the plastic boxes to soak their four feet, maintaining a constant temperature, 25 minutes each time, once a day, 7 days as a course of treatment, and 3 courses of treatment were carried out continuously. During the administration period, all groups were monitored for general conditions and toxic reactions, and mechanical allodynia tests and cold stimulus allergic reactions tests were performed weekly.

[0050] Evaluation indicators and results:

[0051] (1) Mechanical allodynia test

[0052] The evaluation method is: using an electric Von Frey analgesic tester, the probe stimulates the sole of the rat's foot, and the stimulation intensity can be recorded in g. The specific method is: the rat is placed on a metal net and covered with a transparent plexiglass cover. The rat is allowed to adapt to the environment for 15 minutes before the test. After the combing and exploration activities basically disappear, a 4 g Von-Frey fiber is used to stimulate the sole of the rat's hind limb. Each side of the sole is measured 5 times, and the interval between 2 stimulations is more than 6 seconds. The rat's rapid foot-lifting reaction during the stimulation time or immediately after the fiber is removed is recorded as a positive reaction, while the foot-lifting reaction caused by physical activity is not recorded as a positive reaction. During the test, the number of foot-lifting of both hind limbs is recorded, and the percentage of foot retraction is calculated (number of positive reactions ÷ 10 × 100%). The foot-lifting reaction of the rat's sole stimulated by 4 g Von-Frey fiber is a mechanical allodynia reaction. Behavioral tests were performed before modeling (day 0), before drug administration after successful modeling (day 14), and on days 7, 14, and 21 (i.e., day 21, day 28, and day 35) during drug administration. Behavioral tests were performed 1 h after drug administration. The results of behavioral tests are shown in Table 1. The results showed that after successful modeling, rats in the model group and the treatment group showed obvious mechanical hyperalgesia compared with the control group. After drug administration, the hyperalgesia of rats in the treatment group was significantly reduced compared with that in the model group, and the percentage of foot retraction was also significantly reduced. Until the end of the experiment, the difference between the hyperalgesia of rats in the treatment group and the control group was getting smaller and smaller, and after the end of the experiment, the hyperalgesia of rats in the model group was still significantly different from that in the other two groups.

[0053] Table 1 Comparison of paw retraction percentages of rats in each group of Von-Frey 4g at different time points (mean ± SD, %)

[0054]

[0055] Note: Compared with the normal group, *P <0.05, **P <0.01; compared with the model group, #P <0.05, ##P <0.01 (the same below).

[0056] (2) Cold stimulation allergic reaction test

[0057] The evaluation method is as follows: the rat cold stimulus allergic reaction is tested by acetone spraying method in reference ([1] Flatters SJL, Bennett GJ. Ethosuximidereverses paclitaxel- and vincristine-induced painful peripheral neuropathy. [J]. Pain, 2004, 109(1-2):150-161.). The rat is placed on a metal net and covered with a transparent plexiglass cover. The rat is allowed to adapt to the environment for 15 minutes before the test. After the combing and exploration activities have basically disappeared, 50 μL of acetone is sprayed on the surface skin of the rat's hind paw. The time when acetone starts to spray is 0, and the time is counted for 40 seconds. The number of times the rat retracts its paw within 40 seconds is counted. The left and right sides are each 3 times, for a total of 6 times. Behavioral tests were performed before modeling (day 0), before drug administration after successful modeling (day 14), and on days 7, 14, and 21 (i.e., day 21, day 28, and day 35) during drug administration. All behavioral tests were performed 1 hour after drug administration. The results are shown in Table 2. According to Table 2, after successful modeling, the number of foot retraction reflexes after acetone stimulation in the model group and the treatment group was significantly increased compared with the control group, as manifested by lifting the foot, shaking the foot, and licking the foot. After the start of drug administration, the sensory hypersensitivity reaction caused by cold stimulation in the rats in the treatment group began to decrease. Until the end of the experiment, the number of foot retraction reflexes induced by cold stimulation in the treatment group was not much different from that in the control group, while the number of foot retraction reflexes induced by cold stimulation in the model group after the end of the experiment was significantly different from that in the other two groups.

[0058] Table 2 Comparison of the number of cold-stimulated paw withdrawals in rats of each group at different time points (mean ± SD, times)

[0059]

[0060] (3) Detection of differential expression of inflammatory factors IL-1β and TNF-α

[0061] The evaluation method is: ELISA kit detection. 24h after the last administration of rats, each group of rats were anesthetized with 10% chloral hydrate 0.3 mL / kg, and then killed by breaking the neck below the scapula with a rat guillotine, and quickly placed on ice. The L4-L6 spinal cord was immersed in 4% tissue fixative (4% paraformaldehyde in PBS solution) and fixed overnight. After fixation, conventional ethanol gradient dehydration was performed. 100 mg of the above dehydrated tissues were taken from each group and quickly placed in a 1.5 mL EP tube, 1 mL PBS was added, ultrasonic homogenized, centrifuged at 4000 r / min in a 4℃ refrigerated centrifuge for 10 min, and 100 μL of the supernatant was taken. The operation was carried out according to the ELISA kit operating instructions. Standards and samples were added, warmed and reacted, color developed (blue), and the reaction was stopped (blue turned yellow). The absorbance at 450 nm was observed using an enzyme reader, and the detection was performed within 15 min after the reaction was stopped. The calculated concentration was expressed in pg / mg. The results are shown in Table 3. It can be seen that compared with the control group, the levels of IL-1β and TNF-α in the model group increased. Compared with the model group, the levels of IL-1β and TNF-α in the treatment group decreased.

[0062] Table 3 Changes in inflammatory factor levels in rats in each group (mean ± standard deviation, pg / mg)

[0063]

[0064] In summary, oxaliplatin can induce neuropathic pain in rats, which is manifested as allodynia caused by mechanical stimulation, hyperalgesia caused by cold stimulation, and a significant increase in inflammatory factors. After treatment with the Chinese medicine composition involved in the present invention, the allodynia caused by mechanical stimulation and hyperalgesia caused by cold stimulation in the treatment group rats were greatly improved, and the difference was statistically significant compared with the model group, and the inflammatory factors in the treatment group rats were significantly reduced compared with the model group, indicating that the external use of the Chinese medicine composition involved in the present invention can significantly improve the peripheral neuropathy caused by oxaliplatin.

[0065] The applicant declares that the present invention illustrates a Chinese medicine composition for preventing and treating oxaliplatin-induced peripheral neuropathic pain and its preparation method and application through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0066] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0067] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A Chinese medicine composition for external use for preventing and treating oxaliplatin-induced peripheral neuropathic pain, characterized in that: The composition comprises the following raw materials: 1-30 parts of astragalus, 1-30 parts of cassia twig, 3-30 parts of white peony root, 3-30 parts of geranium, 3-20 parts of liquidambar formosana, 1-20 parts of ginger, 1-30 parts of angelica, 5-30 parts of reed root, 2-20 parts of oriental arborvitae, 1-15 parts of motherwort, 1-30 parts of senecio, 2-15 parts of loofah, 2-15 parts of aloe, 1-20 parts of acanthopanax bark, 1-20 parts of jujube, 3-20 parts of curculigo, and 3-20 parts of sappan wood; The preparation method of the external Chinese medicine composition comprises the following steps: S1. Weigh the Chinese medicinal materials by weight, wash and dry the above Chinese medicinal materials for later use; S2. Take the washed and dried astragalus, cinnamon twig, white peony root, ginger, angelica, and acanthopanax bark, add water at a liquid-to-material ratio of 2:1-8:1, soak for 20-120 minutes, then add the remaining Chinese medicinal materials, first boil over high heat, then simmer over low heat for 0.5-3 hours, filter and concentrate to obtain the external Chinese medicine composition.

2. The external Chinese medicine composition according to claim 1, characterized in that: The invention is composed of the following raw materials: 5-20 parts of astragalus, 5-20 parts of cassia twig, 10-20 parts of white peony root, 5-25 parts of geranium, 10-18 parts of rhizoma liquidambar formosana, 5-15 parts of ginger, 5-25 parts of angelica, 10-25 parts of reed root, 5-18 parts of oriental arborvitae leaves, 3-10 parts of motherwort, 2-25 parts of senecio, 5-10 parts of luffa, 5-10 parts of aloe, 5-15 parts of acanthopanax bark, 5-15 parts of jujube, 5-18 parts of curculigo and 5-18 parts of sappan wood.

3. The external Chinese medicine composition according to claim 2, characterized in that: The invention is composed of the following raw materials: 20 parts of astragalus, 20 parts of cassia twig, 18 parts of white peony root, 20 parts of geranium, 15 parts of flue gastrodia elata, 10 parts of ginger, 22 parts of angelica, 16 parts of reed root, 9 parts of oriental arborvitae, 5 parts of motherwort, 20 parts of senecio, 7 parts of luffa, 6 parts of aloe, 10 parts of acanthopanax bark, 10 parts of jujube, 12 parts of curculigo and 12 parts of sappan wood.

4. The external Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The liquid-to-solid ratio in the preparation method is 5:1, the soaking time is 45 minutes, and the decoction time is 2.5 hours.

5. Use of the external Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for preventing and treating oxaliplatin-induced peripheral neuropathic pain.

Citation Information

Patent Citations

  • Application of traditional Chinese medicine composition in chemotherapy of neuropathic pain

    CN116370598A