Use of a Tibetan medicine composition in the preparation of a medicament for preventing and / or treating diabetic peripheral neuropathy

Abstract

The present application relates to the technical field of Tibetan medicine, and particularly relates to application of a Tibetan medicine composition in preparation of a medicine for preventing and / or treating diabetic peripheral neuropathy, wherein the Tibetan medicine composition comprises the following raw medicines: turmeric, mace, sweet cinnamon, actinolite, licorice, artificial musk, dried ginger, Tibetan cumin, Tibetan aconite, Sichuan pepper and alkali flower, and the present application first discovers that the Tibetan medicine composition can improve the sensitivity of nerve endings of a diabetic peripheral nerve injury model mouse, relieve the symptoms of hypalgesia and limb numbness caused by diabetic peripheral nerve injury, and improve the motor nerve conduction velocity of the diabetic peripheral nerve injury model mouse, which indicates that the Tibetan medicine composition can prevent and / or treat diabetic peripheral nerve injury, prevent and / or treat diabetic peripheral neuropathy, and is a potential medicine for diabetic peripheral neuropathy.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of Tibetan medicine, and particularly relates to application of a Tibetan medicine composition in preparation of a medicine for preventing and / or treating diabetic peripheral neuropathy. BACKGROUND

[0002] Diabetes is a group of metabolic diseases caused by multiple causes characterized by chronic hyperglycemia, long-term carbohydrate, fat, protein metabolic disorders due to relative lack of insulin secretion or target cell sensitivity to insulin, which can cause multiple system damage, leading to chronic progressive lesions, functional decline and failure of eye, kidney, nerve, heart, blood vessels and other tissues and organs. Among them, diabetic neuropathy is a complication caused by long-term chronic hyperglycemia on the nervous system, and its clinical incidence can reach 47%-91%. Diabetic neuropathy mainly includes diabetic central neuropathy and peripheral neuropathy, especially the latter.

[0003] The diseases related to diabetic central neuropathy include ischemic cerebrovascular diseases (such as cerebral arteriosclerosis, cerebral infarction, occlusive vascular disease, cerebral ischemia, stroke, hemiplegia, etc.), cognitive dysfunction, epilepsy, chronic encephalopathy, etc. (see Research Progress of Diabetes and Central Nervous System Neuropathy). For diabetic cognitive dysfunction, on the basis of insulin hypoglycemic, western medicine often uses cerebrovascular dilators and neuropeptide combination therapy, and traditional Chinese medicine often uses kidney and blood circulation treatment (see Liang Xiaochun, Research Summary of Chinese and Western Medicine on Diabetic Cognitive Dysfunction, the Seventh National Symposium on Diabetes Combination of Traditional Chinese and Western Medicine). For ischemic cerebrovascular disease, western medicine often uses dehydration or diuretic therapy to reduce intracranial pressure, thrombolytic therapy to improve blood circulation, or anticoagulant therapy to inhibit thrombus formation, etc. Traditional Chinese medicine often uses Banxia Tianma Decoction, Sijunzi Decoction combined with Taohong Siwu Decoction, and Angong Niuhuang Pill, etc. (see Ni Qing, Diagnosis and Treatment of Diabetes Vascular Disease in Combination of Traditional Chinese and Western Medicine).

[0004] The disease symptoms associated with diabetic peripheral neuropathy are mainly sensory disorders, including symmetrical pain and paresthesia in the limbs, more common in lower limbs than in upper limbs, intermittent or continuous onset, burning or electric shock-like pain, aggravated at rest or at night. Paresthesia and numbness in the distal extremities, crawling, and ant-like sensation, can present as "glove" or "sock" sensory disorders. With the development of the disease, motor disorders and even diabetic foot may occur, which is the main cause of non-traumatic amputation in current clinical practice. Currently, the drugs used in the treatment of diabetic peripheral neuropathy in clinical practice mainly include the following categories: (1) opioid analgesics, such as morphine; (2) antidepressants, such as naproxen; (3) local anesthetics, such as lidocaine; (4) neurotrophic drugs, such as mecobalamin. However, traditional drugs still have various defects, such as high side effects and adverse reactions and high cost of opioid analgesics, antidepressants, and local anesthetics, limited or insufficient efficacy of mecobalamin, and slow onset. Therefore, there is an urgent need for a drug that can effectively prevent and / or treat diabetic peripheral neuropathy.

[0005] Bailai ointment is composed of turmeric, mace, sweet cinnamon, actinolite, licorice, artificial musk, dried ginger, Tibetan cumin, Tibetan aconite, Sichuan pepper, and alkali flower. It has the effect of relaxing muscles and activating collaterals. It is widely used in clinic for treating white vein disease, paralysis, hemiplegia, tendon rigidity, meridian and tendon injury caused by trauma, hand and foot spasm, claudication, and the like. Currently, there is no research report on the use of Bailai ointment or related Tibetan medicine compositions for preventing and treating diabetic peripheral neuropathy. SUMMARY

[0006] Therefore, the purpose of the present application is to provide a Tibetan medicine composition for use in the preparation of a drug for preventing and / or treating diabetic peripheral neuropathy.

[0007] Specifically, the Tibetan medicine composition comprises the following raw medicinal materials: turmeric, mace, sweet cinnamon, actinolite, licorice, artificial musk, dried ginger, Tibetan cumin, Tibetan aconite, Sichuan pepper, and alkali flower.

[0008] As a specific embodiment, the diabetic peripheral neuropathy is caused by diabetic peripheral nerve injury.

[0009] As a preferred embodiment, the Tibetan medicine composition comprises the following raw medicinal materials: turmeric 30-40 parts, mace 10-15 parts, sweet cinnamon 15-25 parts, actinolite 10-15 parts, licorice 15-20 parts, artificial musk 0.1-0.2 parts, dried ginger 20-30 parts, Tibetan cumin 25-35 parts, Tibetan aconite 15-20 parts, Sichuan pepper 10-15 parts, and alkali flower 15-20 parts, in terms of weight fraction.

[0010] As a preferred embodiment, the Tibetan medicine composition is a composition obtained by mixing each raw medicine powder, or an extract obtained by extracting each raw medicine after mixing, or a composition obtained by mixing each extract obtained by extracting.

[0011] As a preferred embodiment, the medicine is a Tibetan medicine composition processed into a conventional oral dosage form or a topical dosage form by a conventional preparation process.

[0012] As a preferred embodiment, the oral dosage form is selected from granules, pills, capsules, tablets or oral liquids, and the topical dosage form is selected from ointments, plasters, aerosols, sprays, wet compresses, lotions or gels, and the conventional preparation process includes medicine powdering, decocting, percolating, leaching, ultrasonic or steam distillation.

[0013] As a preferred embodiment, the medicine further comprises a pharmaceutically acceptable carrier; the pharmaceutically acceptable carrier is selected from at least one of a pharmaceutically acceptable solvent, a solubilizer, a cosolvent, an emulsifier, a coloring agent, a binder, a disintegrant, a filler, a lubricant, a wetting agent, an osmotic pressure regulator, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an aromatic agent, an anti-adhesion agent, an integrating agent, a penetration enhancer, a pH regulator, a buffer, a plasticizer, a surfactant, a thickening agent, an inclusion agent, a humectant, an absorbent, a diluent, a flocculating agent, a deflocculating agent, a filtration aid, a release retardant, a high molecular skeleton material and a film-forming material.

[0014] As a preferred embodiment, the medicine preparation is an ointment, and the ointment further comprises an ointment base.

[0015] In a more preferred embodiment, the mass ratio of the Tibetan medicine composition and the ointment base is 0.5:9.5-5:5.

[0016] As a preferred embodiment, the ointment base comprises polysorbate 80, liquid paraffin, glycerol, hydroxybenzoate and water, and preferably, the mass ratio of polysorbate 80, liquid paraffin, glycerol, hydroxybenzoate and water is 1-10:20-60:20-60:0.5-2:200-400.

[0017] As a preferred embodiment, the preparation method of the ointment comprises the following steps:

[0018] Turmeric, nutmeg, sweet cinnamon, actinolite, licorice, dried ginger, Tibetan cumin, Tibetan aconite, Sichuan pepper and alkali flowers are taken, powdered, mixed with the ointment base, and mixed with artificial musk to obtain the ointment.

[0019] The application also provides a use of the Tibetan medicine composition or the medicine preparation of any of the application in the preparation of a medicine, and the medicine has the following uses:

[0020] (1) treating diabetic peripheral nerve injury, improving motor nerve conduction velocity;

[0021] (3) relieving paresthesia caused by diabetic peripheral nerve injury.

[0022] Pharmacological experimental studies show that the Tibetan medicine composition can improve the sensitivity of the nerve endings of diabetic peripheral nerve injury model mice, relieve the symptoms of hypalgesia and limb numbness caused by diabetic peripheral nerve injury. Moreover, the Tibetan medicine composition can prevent and / or treat diabetic peripheral nerve injury and improve the motor nerve conduction velocity of diabetic peripheral nerve injury model mice, indicating that the Tibetan medicine composition can prevent and / or treat diabetic peripheral neuropathy and is a potential drug for diabetic peripheral neuropathy. DETAILED DESCRIPTION

[0023] The following examples are provided to better further understand the present application and are not limited to the best mode, and do not limit the content and scope of protection of the present application. Any person under the inspiration of the present application or the combination of the present application with other prior art features can obtain any product identical or similar to the present application, which falls within the scope of protection of the present application.

[0024] In the examples, the specific experimental steps or conditions are not specified, and can be performed according to the conventional experimental steps described in the literature. The reagents or instruments used are not specified by the manufacturer, and are conventional reagent products that can be obtained by purchase.

[0025] Example 1 ointment

[0026] The present embodiment provides a Tibetan medicine composition, and the raw material formula is as follows: turmeric 36.3g, mace 12.1g, sweet cinnamon 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, and alkali flower 18.2g.

[0027] The ointment of the above-mentioned Tibetan medicine composition, with a total mass of 1000g, comprises: turmeric 36.3g, mace 12.1g, sweet cinnamon 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, and alkali flower 18.2g, liquid paraffin 80g, glycerol 80g, 10g polysorbate 80, hydroxybenzyl 10g, and the balance is water.

[0028] Preparation: according to the above formula turmeric, nutmeg, sweet cinnamon, actinolite, licorice, dried ginger, Amomum tsangii, Acorus gramineus, Zanthoxylum bungeanum and alkali flowers are weighed, crushed into coarse powder, mixed, and then liquid paraffin, glycerol, polysorbate 80, hydroxybenzyl alcohol and water are added. Paste is prepared at 80°C, cooled to 38°C, and then artificial musk is added and stirred evenly to obtain 1000g of ointment. The ointment is placed at room temperature for 4.5 hours and then packaged.

[0029] Example 2 wet compress

[0030] The present example provides a Tibetan medicine composition, and the raw material formula is as follows: turmeric 30g, nutmeg 15g, sweet cinnamon 15g, actinolite 15g, licorice 15g, artificial musk 0.2g, dried ginger 20g, Amomum tsangii 35g, Acorus gramineus 15g, Zanthoxylum bungeanum 15g, and alkali flowers 20g.

[0031] The wet compress of the above-mentioned Tibetan medicine composition includes: turmeric 36.3g, nutmeg 12.1g, sweet cinnamon 19.4g, actinolite 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Amomum tsangii 31.5g, Acorus gramineus 17.0g, Zanthoxylum bungeanum 12.1g, and alkali flowers 18.2g.

[0032] Preparation: according to the above formula turmeric, nutmeg, sweet cinnamon, actinolite, licorice, artificial musk, dried ginger, Amomum tsangii, Acorus gramineus, Zanthoxylum bungeanum, and alkali flowers are weighed, crushed into coarse powder, mixed, and then soaked in an appropriate amount of 60vt% ethanol. Then, percolation is performed using 60vt% ethanol as the solvent, and the percolate is collected to obtain the percolate of the Tibetan medicine composition. Non-woven fabric is used as the carrier and immersed in the filtrate, and then the product is sliced, sealed and packaged to obtain the wet compress.

[0033] Example 3 tablet

[0034] The present example provides a Tibetan medicine composition, and the raw material formula is as follows: turmeric 40g, nutmeg 10g, sweet cinnamon 25g, actinolite 10g, licorice 20g, artificial musk 0.1g, dried ginger 30g, Amomum tsangii 25g, Acorus gramineus 20g, Zanthoxylum bungeanum 10g, and alkali flowers 15g.

[0035] The tablet of the above-mentioned Tibetan medicine composition includes: turmeric 40g, nutmeg 10g, sweet cinnamon 25g, actinolite 10g, licorice 20g, artificial musk 0.1g, dried ginger 30g, Amomum tsangii 25g, Acorus gramineus 20g, Zanthoxylum bungeanum 10g, alkali flowers 15g, 90g starch, and 5g magnesium stearate.

[0036] Preparation: according to the above formula turmeric, nutmeg, sweet cinnamon, actinolite, licorice, dried ginger, Amomum tsangii, Acorus gramineus, Zanthoxylum bungeanum, Zanthoxylum bungeanum, artificial musk and alkali flowers are weighed, crushed into coarse powder, mixed, and then starch is added for mixing, granulation, and magnesium stearate is added for tabletting.

[0037] Example 4 ointment

[0038] The present example provides a Tibetan medicine composition, the raw material formula is as follows: turmeric 40g, nutmeg 10.5g, sweet pine 25g, sunstone 10.2g, licorice 20g, artificial musk 0.1g, dried ginger 30g, Tibetan cumin 25.5g, aconite 20g, pepper 10.3g, alkali flower 15.5g.

[0039] The ointment of the above-mentioned Tibetan medicine composition, with a total mass of 4000g, comprises: turmeric 40g, nutmeg 10g, sweet pine 25g, sunstone 10g, licorice 20g, artificial musk 0.1g, dried ginger 30g, Tibetan cumin 25g, aconite 20g, pepper 10g, alkali flower 15g, liquid paraffin 320g, glycerol 320g, 80g polysorbate 80, hydroxybenzyl 8g, and the balance is water.

[0040] Method of preparation: according to the above formula, turmeric, nutmeg, sweet pine, sunstone, licorice, dried ginger, Tibetan cumin, aconite, pepper and alkali flower are weighed and crushed into coarse powder, mixed, liquid paraffin, glycerol, polysorbate 80, hydroxybenzyl and water are added. Stir at 80°C to make ointment, cool to 38°C, add artificial musk, stir evenly, prepare 1000g of ointment, place at room temperature for 4 hours, and then pack.

[0041] Example 5 ointment

[0042] The present example provides a Tibetan medicine composition, the raw material formula is as follows: turmeric 36.3g, nutmeg 12.1g, sweet pine 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, aconite 17.0g, pepper 12.1g, alkali flower 18.2g.

[0043] The ointment of the above-mentioned Tibetan medicine composition, with a total mass of 400g, comprises: turmeric 36.3g, nutmeg 12.1g, sweet pine 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, aconite 17.0g, pepper 12.1g, alkali flower 18.2g, liquid paraffin 20g, glycerol 20g, 10g polysorbate 10, hydroxybenzyl 2g, and the balance is water.

[0044] Method of preparation: according to the above formula, turmeric, nutmeg, sweet pine, sunstone, licorice, dried ginger, Tibetan cumin, aconite, pepper and alkali flower are weighed and crushed into coarse powder, mixed, liquid paraffin, glycerol, polysorbate 80, hydroxybenzyl and water are added. Stir at 80°C to make ointment, cool to 38°C, add artificial musk, stir evenly, prepare 1000g of ointment, place at room temperature for 4 hours, and then pack.

[0045] Gelatin of the Tibetan medicine composition

[0046] The present example provides a Tibetan medicine composition, the raw material formula is as follows: turmeric 36.3g, mace 12.1g, sweetgrass 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, alkali flower 18.2g.

[0047] The gelatin of the above-mentioned Tibetan medicine composition, with a total mass of 1000g, comprises: turmeric 36.3g, mace 12.1g, sweetgrass 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, alkali flower 18.2g, carbomer 940 10.0g, glycerol 30g, hydroxybenzyl 2.0g, 3.0g polysorbate 80, and the rest is water.

[0048] The preparation method is as follows: according to the above formula, turmeric, mace, sweetgrass, sunstone, licorice, dried ginger, Tibetan cumin, Tibetan aconite, Sichuan pepper and alkali flower are weighed and crushed into coarse powder, mixed to obtain medicinal powder. Carbomer 940 is swelled in 200g water at 70℃ overnight, and then glycerol, hydroxybenzyl, polysorbate 80 and medicinal powder are added and stirred to prepare gelatin. Artificial musk and the rest of water are added, stirred evenly, and 1000g of gelatin is prepared and packaged.

[0049] Example 7 Plaster

[0050] The present example provides a Tibetan medicine composition, the raw material formula is as follows: turmeric 36.3g, mace 12.1g, sweetgrass 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, alkali flower 18.2g.

[0051] The plaster of the above-mentioned Tibetan medicine composition comprises: turmeric 36.3g, mace 12.1g, sweetgrass 19.4g, sunstone 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, alkali flower 18.2g, rubber 30g, rosin 50g, zinc oxide 40g.

[0052] The preparation method is as follows: according to the above formula, turmeric, mace, sweetgrass, sunstone, licorice, dried ginger, Tibetan cumin, Tibetan aconite, Sichuan pepper and alkali flower are weighed and crushed into coarse powder, mixed to obtain medicinal powder. Carbomer 940 is swelled in 200g water at 70℃ overnight, and then glycerol, hydroxybenzyl, polysorbate 80 and medicinal powder are added and stirred to prepare gelatin. Artificial musk and the rest of water are added, stirred evenly, and 1000g of gelatin is prepared and packaged. 3The paste is prepared by mixing the above-mentioned ingredients with ethanol, filtering, adding water to 1000ml, filtering again, and then dispensing into bottles with spray valves.

[0053] Example 8 Aerosol

[0054] The present example provides a Tibetan medicine composition, and the raw material formula is as follows: turmeric 36.3g, nutmeg 12.1g, sweet cinnamon 19.4g, actinolite 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, and alkali flower 18.2g.

[0055] The aerosol of the above-mentioned Tibetan medicine composition comprises: turmeric 36.3g, nutmeg 12.1g, sweet cinnamon 19.4g, actinolite 12.1g, licorice 17.0g, artificial musk 0.17g, dried ginger 24.2g, Tibetan cumin 31.5g, Tibetan aconite 17.0g, Sichuan pepper 12.1g, alkali flower 18.2g, methylparaben 2.0g, polysorbate 80 20.0g, and ethanol 100g.

[0056] Method: According to the above formula, turmeric, nutmeg, sweet cinnamon, actinolite, licorice, dried ginger, Tibetan cumin, Tibetan aconite, Sichuan pepper, and alkali flower are weighed, and then 10 times the amount of ethanol is used for percolation. The percolate is recovered by ethanol, and then concentrated to a density of 1.05-1.10g / cm 3 The paste is prepared by mixing the above-mentioned ingredients with ethanol, filtering, adding water to 1000ml, filtering again, and then dispensing into bottles with spray valves.

[0057] Experimental Example 1

[0058] 1. Experimental animals: male (Lepr) ko / ko genotype mice as model mice, SPF level, 8 weeks old, body weight 35-55g, 80. Male (Lepr) wt / wt genotype mice as control mice, SPF level, 8 weeks old, body weight 20-30g, 10. Experimental animals are provided by Jiangsu Jizhuangkang Biotechnology Co., Ltd.

[0059] 2. Preparation of test drugs

[0060] The ointment prepared in Example 1 of the present application is used, and another ointment base is used as a placebo to give the test animals according to the dosage shown in Table 1.

[0061] The ointment base used in the placebo group is prepared by mixing liquid paraffin 80g, glycerol 80g, polysorbate 80 10g, methylparaben 10g, and water 628g at 80°C, stirring to make paste, and then placing at room temperature for 4.5 hours.

[0062] Table 1 Experimental dose design

[0063] Dose of administration Area of administration (cm 2 )]]> Low dose group of test drug 0.1 g of crude drug amount / kg of animal body weight 0.5×0.5 Medium dose group of test drug 0.3 g of crude drug amount / kg of animal body weight 0.5×1.5 High dose group of test drug 0.9 g of crude drug amount / kg of animal body weight 1.5×1.5 Placebo group (model control group) 0 g of crude drug amount / kg of animal body weight 1.5×1.5

[0064] 3. Experimental method

[0065] (1) Administration method: Male (Lepr) ko / ko genotype db / db mice were used to naturally form a diabetic peripheral neuropathy model, and the effects of different doses of the test drug on peripheral neuropathy were observed. Male (Lepr) wt / wt genotype mice were used as normal control group. Animals were allowed to freely ingest food and water, and after (Lepr) ko / ko genotype mice developed hyperglycemia, MCV, SCV and blood glucose were measured once a week. When MCV showed a significant decrease in conduction velocity, the model mice were randomly and evenly divided into groups according to MCV, pain threshold and blood glucose, and randomly divided into 5 groups, namely model control group, test drug group (low dose group, medium dose group and high dose group), positive drug group, 10 in each group. The thighs of the mice were shaved, and the placebo and test drug were applied to the sciatic nerve of the mouse leg in the model control group and the test drug group, respectively, once a day, and the thickness of each dose group was consistent. The area is shown in the table above, and the administration period is 8 weeks. Among them, the low dose group was given 0.1 g of crude drug / kg of animal body weight, the medium dose group was given 0.3 g of crude drug / kg of animal body weight, and the high dose group was given 0.9 g of crude drug / kg of animal body weight. The model control group was given the same volume of ointment base as the high dose group. The positive drug group was given intragastrically once a day with methylcobalamin solution (solvent: distilled water, mass concentration: 0.015 mg / ml), and the intragastric volume was 20 mL / kg of animal body weight. The administration period was 8 weeks.

[0066] (2) Test of pain threshold

[0067] The mice in each group were placed on the suspended wire grid inside the transparent glass observation box and allowed to move freely. After their grooming and exploring activities basically disappeared, a standardized fiber was used to stimulate the plantar part vertically for 5 seconds, and the stimulation intensity at which the experimental mice showed rapid foot withdrawal or foot licking reaction was recorded. Measure 3 times, with an interval of (3-5) min each time, and take the average value of 3 times as the pain threshold of the mouse. The grouping and determination of the pain threshold were performed every two weeks after administration.

[0068] (3) Test of motor nerve conduction velocity

[0069] The experiment employed an electronic stimulator and a physiological signal data acquisition system. Mice were anesthetized and fixed on a mouse board with their left hind leg straightened and immobilized. A stimulating electrode was inserted at the left sciatic notch, and a recording electrode was placed at the ankle joint. A reference electrode was positioned between the stimulating and recording electrodes. All electrodes used in the experiment were needle electrodes. Square wave stimulation was used with a pulse width of 1 ms, with a 5-second interval between each stimulus. The latency period, i.e., the time from the generation of stimulation by the electrode to the appearance of a potential in the muscle, was recorded. Three measurements were taken for each rat, and the average value was calculated. The length between the stimulating and recording electrodes was measured using calipers as the conduction distance. MCV = motor nerve conduction distance / latency period. Measurements were taken every two weeks during grouping and after drug administration.

[0070] 4. Experimental Results

[0071] (1) Results of the effect on pain threshold in spontaneously diabetic mice

[0072] Before drug administration, the pain threshold of mice in the model control group was significantly higher than that in the normal control group (2.3±0.6 vs 1.1±0.2 g, P<0.001), indicating that spontaneously diabetic mice had developed decreased pain perception. There were no significant differences between the drug administration groups and the model control group (P>0.05), and the results are shown in Table 2.

[0073] During the administration period (2–8 weeks), the pain threshold of the model control group was consistently significantly higher than that of the normal control group (P<0.01–0.001). Compared with the model control group, during the administration period (2–8 weeks), the test drug at doses of 0.1, 0.3, and 0.9 g crude drug / kg reduced the pain threshold of the model mice to varying degrees (P<0.05–0.001); during the administration period (2–8 weeks), the positive control drug methylcobalamin at 0.3 mg / kg reduced the pain threshold of the model mice to varying degrees (P<0.05–0.001). The results are shown in Table 2.

[0074] Compared with the control group, the difference between the test drug (0.9 g crude drug / kg) and the control group was calculated. After 4–8 weeks of administration, the pain threshold of the model mice was reduced to varying degrees (P<0.05). After 4–8 weeks of administration, the positive control drug (methylcobalamin) (0.3 mg / kg) was reduced to varying degrees (P<0.05). The results are shown in Table 3.

[0075] Table 2. Effects of the test drug on the pain threshold in spontaneously diabetic mice. n=10)

[0076]

[0077] Compared with the normal control group, △△ P<0.01, △△△ P<0.001; Compared with the model control group, *P<0.05, **P<0.01, ***P<0.001; n: sample size.

[0078] Table 3 Effects of test drugs on pain threshold difference of spontaneous diabetic mice n=10

[0079]

[0080] Compared with model control group, *P<0.01; n: sample number.

[0081] By analysis, it is known that test drugs can reduce pain threshold of model mice, and there is no significant difference in efficacy with methycobal, which shows that test drugs can improve nerve ending sensitivity of diabetic model mice with nerve lesion. Therefore, it can relieve symptoms of limb numbness of patients with diabetic peripheral neuropathy.

[0082] (2) Effects of test drugs on motor nerve conduction velocity of spontaneous diabetic peripheral neuropathy mice

[0083] Before administration, motor nerve conduction velocity of model control group mice was significantly lower than that of normal control group (4.29±0.67 vs 5.90±1.18 m / s, P<0.01;). Compared with model control group, no significant difference was found in each administration group (P>0.05), and the results are shown in Table 4.

[0084] After administration (2-8) weeks, motor nerve conduction velocity of model control group mice was always significantly higher than that of normal control group (P<0.05-0.001). Compared with model control group, test drugs 0.3, 0.9 g crude drug / kg could improve motor nerve conduction velocity of model mice in different degrees (P<0.05-0.001) after administration (4-8) weeks; positive drug methycobal 0.3 mg / kg could improve motor nerve conduction velocity of model mice in different degrees (P<0.05-0.01) after administration (6-8) weeks, and the results are shown in Table 4.

[0085] Compared with before administration, test drug 0.9 g crude drug / kg could improve motor nerve conduction velocity of model mice in different degrees (P<0.05) after administration (4-8) weeks. Positive drug methycobal 0.3 mg / kg could improve motor nerve conduction velocity of model mice in different degrees (P<0.05) after administration (4-8) weeks, and the results are shown in Table 5.

[0086] Table 4 Effects of test drugs on MCV of spontaneous diabetic mice n=10

[0087]

[0088] Compared with normal control group, △ P<0.05, △△ P<0.01,△△△ P<0.001; *P<0.05, **P<0.01, ***P<0.001 compared with model control group; n: sample number.

[0089] Table 5 Effect of different drugs on MCV difference of spontaneous diabetes mellitus mice n=10

[0090]

[0091] Compared with model control group, * P<0.05; n: sample number.

[0092] Conclusion: Using spontaneous diabetes mellitus peripheral neuropathy mouse model, the test drug 0.1, 0.3, 0.9g crude drug / kg continuous administration (2-8) weeks, can improve the pain threshold of model mice, sciatic nerve motor nerve conduction velocity, indicating that the test drug can improve the sciatic motor nerve conduction velocity of diabetic mice to relieve sensory disturbance of diabetic model mice.

[0093] Obviously, the above examples are only examples for clearly illustrating, but not limit the embodiments. For those skilled in the art, on the basis of the above description, other different forms of changes or variations can also be made. Here, it is not necessary and also impossible to enumerate all the embodiments. The obvious changes or variations derived therefrom are still within the protection scope of the present application.

Claims

1. Use of a Tibetan medicine composition in the preparation of a medicament for the prevention and / or treatment of diabetic peripheral neuropathy, characterized in that, The Tibetan medicine composition is prepared from the following raw medicinal materials in parts by weight: turmeric 30-40 parts, mace 10-15 parts, sweet cinnamon 15-25 parts, actinolite 10-15 parts, licorice 15-20 parts, artificial musk 0.1-0.2 parts, dried ginger 20-30 parts, Tibetan cumin 25-35 parts, Tibetan aconite 15-20 parts, Sichuan pepper 10-15 parts, and alkali flower 15-20 parts.

2. Use according to claim 1, characterized in that, The Tibetan medicine composition is a composition obtained by mixing the raw medicinal materials after being ground, or an extract obtained by extracting the raw medicinal materials after being mixed, or a composition obtained by mixing the extracts obtained by extracting the raw medicinal materials respectively.

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