CN113181331A

CN113181331A - Application of Tibetan medicine composition in preparing medicine for preventing and/or treating diabetic peripheral neuropathy

Info

Publication number: CN113181331A
Application number: CN202110587145.6A
Authority: CN
Inventors: 雷菊芳; 刘凯列; 陈维武; 陈伦举; 车向宜; 李峰; 刁习霞
Original assignee: Tibetan Cheezheng Tibetan Medicine Co ltd
Current assignee: Tibetan Cheezheng Tibetan Medicine Co ltd
Priority date: 2021-05-27
Filing date: 2021-05-27
Publication date: 2021-07-30
Also published as: WO2022247922A1

Abstract

The invention relates to the technical field of Tibetan medicine, in particular to application of a Tibetan medicine composition in preparing a medicine for preventing and/or treating diabetic peripheral neuropathy, wherein the Tibetan medicine composition comprises the following raw material medicines: the invention firstly discovers that the Tibetan medicine composition can improve the sensitivity of nerve endings of a mouse with a diabetic peripheral nerve injury model, relieve hypoalgesia and limb numbness symptoms caused by the diabetic peripheral nerve injury, and improve the motor nerve conduction speed of the mouse with the diabetic peripheral nerve injury model, so that the Tibetan medicine composition can prevent and/or treat the diabetic peripheral nerve injury and prevent and/or treat the diabetic peripheral neuropathy and is a potential medicine for the diabetic peripheral neuropathy.

Description

Application of Tibetan medicine composition in preparing medicine for preventing and/or treating diabetic peripheral neuropathy

Technical Field

The invention relates to the technical field of Tibetan medicine, in particular to application of a Tibetan medicine composition in preparing a medicine for preventing and/or treating diabetic peripheral neuropathy.

Background

Diabetes mellitus is a group of metabolic diseases which are caused by multiple causes and are characterized by chronic hyperglycemia, and long-term carbohydrate, fat and protein metabolic disorders caused by relative insufficient insulin secretion or reduced sensitivity of target cells to insulin can cause multiple system damages, so that chronic progressive lesions, hypofunction and failure of tissues and organs such as eyes, kidneys, nerves, hearts, blood vessels and the like can be caused. The diabetic neuropathy is a complication caused by damage of chronic hyperglycemia to a nervous system, and the clinical morbidity of the diabetic neuropathy can reach 47% -91%. Diabetic neuropathy mainly includes diabetic central neuropathy and peripheral neuropathy, which are more common in the latter.

The diseases related to diabetic central neuropathy include ischemic cerebrovascular diseases (such as cerebral arteriosclerosis, cerebral infarction, occlusive angiopathy, cerebral ischemia, apoplexy, paraquat, etc.), cognitive dysfunction, epilepsy, chronic encephalopathy, etc. (see "development of research on diabetes and central nervous system neuropathy"). For cognitive dysfunction of diabetes, on the basis of reducing blood sugar by insulin, the western medicine mostly adopts combined treatment of a cerebral vasodilator and neuropeptide, and the traditional Chinese medicine mostly adopts a traditional Chinese medicine prescription for tonifying kidney, improving intelligence, promoting blood circulation and removing blood stasis (see Liangxiao spring, the summary of research and western medicine for cognitive function impairment of diabetes, and the seventh national conference of diabetes and western medicine combined with diabetes). For ischemic cerebrovascular diseases, the western medicine mostly adopts dehydrating agent or diuretic therapy to reduce intracranial pressure, thrombolytic therapy to improve blood circulation, or anticoagulant therapy to inhibit thrombosis, and other treatment means. The traditional Chinese medicine is mainly treated by pinellia ternate and tall gastrodia tuber decoction, Sijunzi decoction, peach red Siwu decoction, Angong Niuhuang pills and the like (see Niqing, the diagnosis and treatment of the combination of the traditional Chinese medicine and the Western medicine for treating the diabetes mellitus and the vascular disease).

The disease symptoms associated with diabetic peripheral neuropathy are mainly sensory disturbances including symmetric pain and paresthesia in the extremities, more frequent in the lower extremities than in the upper extremities, intermittent or persistent attacks, burning or shock-like pain, and aggravated at rest or at night. The sensation of the distal extremities of the limbs is abnormal and has the sensation of numbness, worm crawling and ant walking, which can be felt as "gloves" or "socks". Dyskinesia and even diabetic feet can appear along with the development of the disease, and are the main reason of non-traumatic amputation in clinic at present. At present, the medicines clinically used in western medicine for treating diabetic peripheral neuropathy mainly include the following types: (1) opioid analgesics, such as morphine; (2) antidepressants, such as naproxen; (3) local anesthetics, such as lidocaine; (4) neurotrophins, mecobalamin, and the like. However, the traditional medicines still have various defects, such as high probability of side effects and adverse reactions of opioid analgesics, antidepressants and local anesthetics, high cost, limited or insufficient efficacy of mecobalamin and slow effect. Therefore, there is a high necessity for a drug effective for the prevention and/or treatment of diabetic peripheral neuropathy.

The white vein ointment is prepared from Curcuma rhizome, semen Myristicae, radix Et rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, artificial Moschus, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli, and trona. Has effects of relaxing muscles and tendons and activating collaterals. The medicine is widely used for treating white pulse disease, paralysis, hemiplegia, tendon rigidity, meridian and tendon fracture, hand and foot spasm, claudication and the like caused by trauma in clinic. At present, no research report on the prevention and treatment of diabetic peripheral neuropathy by adopting white vein ointment or related Tibetan medicine compositions is available.

Disclosure of Invention

Therefore, the invention aims to provide the application of the Tibetan medicine composition in preparing the medicine for preventing and/or treating diabetic peripheral neuropathy.

Specifically, the Tibetan medicine composition comprises the following raw material medicines: turmeric, nutmeg, nardostachys chinensis, actinolite, licorice, artificial musk, dried ginger, caraway, calamus, zanthoxylum and trona.

In a specific embodiment, the diabetic peripheral neuropathy is caused by diabetic peripheral nerve damage.

As a preferred embodiment, the Tibetan medicine composition comprises the following raw material medicines in parts by weight: 30-40 parts of turmeric, 10-15 parts of nutmeg, 15-25 parts of nardostachys chinensis, 10-15 parts of actinolite, 15-20 parts of liquorice, 0.1-0.2 part of artificial musk, 20-30 parts of dried ginger, 25-35 parts of caraway, 15-20 parts of acorus calamus, 10-15 parts of pepper and 15-20 parts of trona.

In a preferred embodiment, the Tibetan medicine composition is a composition obtained by crushing and mixing the raw material medicines, or an extract obtained by mixing the raw material medicines and then extracting the mixture by a conventional extraction method, or a composition obtained by mixing the extracts obtained by respectively extracting the raw material medicines.

As a preferable embodiment, the medicament is an oral dosage form or an external dosage form which is processed into the conventional dosage form in the field by the conventional preparation process of the Tibetan medicine composition.

As a preferred embodiment, the oral dosage form is selected from granules, pills, capsules, tablets or oral liquid, the external dosage form is selected from ointment, emplastrum, aerosol, spray, wet dressing, lotion or gel, and the conventional preparation process comprises the steps of crushing, decocting, percolating, leaching, ultrasonic treatment or steam distillation of medicinal materials.

As a preferred embodiment, the medicament further comprises a pharmaceutically acceptable carrier; the pharmaceutically acceptable carrier is selected from at least one of pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adherents, integration agents, permeation enhancers, pH regulators, buffers, plasticizers, surfactants, thickeners, encapsulation agents, humectants, absorbents, diluents, flocculants, deflocculants, filter aids, release retardants, polymeric matrix materials, and film-forming materials.

As a preferred embodiment, the pharmaceutical formulation is an ointment, which further comprises an ointment base.

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

as a preferred embodiment, the ointment base comprises polysorbate 80, liquid paraffin, glycerin, methylparaben and water, and preferably, the mass ratio of polysorbate 80, liquid paraffin, glycerin, methylparaben and water is 1-10: 20-60: 20-60: 0.5-2: 200-400.

As a preferred embodiment, the ointment is prepared by a method comprising the steps of:

pulverizing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona, mixing with ointment base, adding artificial Moschus, and mixing.

The invention also provides an application of the Tibetan medicine composition or the pharmaceutical preparation in preparing a medicine, wherein the medicine has the following applications:

(1) treating diabetic peripheral nerve injury, and increasing motor nerve conduction velocity;

(3) relieving abnormal sensation caused by diabetic peripheral nerve injury.

Pharmacological experimental research shows that the Tibetan medicine composition can improve the sensitivity of nerve endings of a diabetic peripheral nerve injury model mouse and relieve hypoalgesia and limb numbness symptoms caused by diabetic peripheral nerve injury. The Tibetan medicine composition can prevent and/or treat diabetic peripheral nerve injury, and improve the motor nerve conduction velocity of a diabetic peripheral nerve injury model mouse, so that the Tibetan medicine composition can prevent and/or treat diabetic peripheral neuropathy and is a potential medicine for the diabetic peripheral neuropathy.

Detailed Description

The following examples are provided to further understand the present invention, not to limit the scope of the present invention, but to provide the best mode, not to limit the content and the protection scope of the present invention, and any product similar or similar to the present invention, which is obtained by combining the present invention with other prior art features, falls within the protection scope of the present invention.

The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.

EXAMPLE 1 ointment

The embodiment provides a Tibetan medicine composition, which comprises the following raw materials: 36.3g of curcuma longa, 12.1g of nutmeg, 19.4g of nardostachys chinensis, 12.1g of actinolite, 17.0g of liquorice, 0.17g of artificial musk, 24.2g of dried ginger, 31.5g of caraway, 17.0g of calamus, 12.1g of pepper and 18.2g of trona.

The ointment of the Tibetan medicine composition comprises the following components in percentage by mass of 1000 g: 36.3g of curcuma longa, 12.1g of nutmeg, 19.4g of nardostachys chinensis, 12.1g of actinolite, 17.0g of liquorice, 0.17g of artificial musk, 24.2g of dried ginger, 31.5g of caraway, 17.0g of calamus, 12.1g of pepper, 18.2g of trona, 80g of liquid paraffin, 80g of glycerol, 10g of polysorbate 80, 10g of methylparaben and the balance of water.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona according to the above formula, pulverizing into coarse powder, mixing, and adding liquid paraffin, glycerol, polysorbate 80, methyl hydroxybenzoate and water. Stirring at 80 deg.C to obtain paste, cooling to 38 deg.C, adding artificial Moschus, stirring to obtain ointment 1000g, standing at room temperature for 4.5 hr, and packaging.

Example 2 Wet application agent

The embodiment provides a Tibetan medicine composition, which comprises the following raw materials: 30g of curcuma longa, 15g of nutmeg, 15g of nardostachys chinensis, 15g of actinolite, 15g of liquorice, 0.2g of artificial musk, 20g of dried ginger, 35g of caraway, 15g of calamus, 15g of pepper and 20g of trona.

The wet compress agent of the Tibetan medicine composition comprises the following raw materials: 36.3g of curcuma longa, 12.1g of nutmeg, 19.4g of nardostachys chinensis, 12.1g of actinolite, 17.0g of liquorice, 0.17g of artificial musk, 24.2g of dried ginger, 31.5g of caraway, 17.0g of calamus, 12.1g of pepper and 18.2g of trona.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, artificial Moschus, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona according to the above formula, pulverizing into coarse powder, and mixing; adding appropriate amount of 60 vt% ethanol, soaking, percolating with 60 vt% ethanol as solvent, collecting percolate to obtain Tibetan medicinal composition percolate, making non-woven fabric into carrier, soaking in the fine filtrate, slicing, sealing, and packaging to obtain wet compress agent.

EXAMPLE 3 tablets

The embodiment provides a Tibetan medicine composition, which comprises the following raw materials: 40g of curcuma longa, 10g of nutmeg, 25g of rhizoma nardostachyos, 10g of actinolite, 20g of liquorice, 0.1g of artificial musk, 30g of dried ginger, 25g of caraway, 20g of calamus, 10g of pepper and 15g of trona.

The raw material formula of the tablet of the Tibetan medicine composition comprises: 40g of curcuma longa, 10g of nutmeg, 25g of rhizoma nardostachyos, 10g of actinolite, 20g of liquorice, 0.1g of artificial musk, 30g of dried ginger, 25g of caraway, 20g of calamus, 10g of pepper, 15g of trona, 90g of starch and 5g of magnesium stearate.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli, artificial Moschus and trona according to the above formula, pulverizing into coarse powder, mixing, adding starch, mixing, granulating, adding magnesium stearate, and tabletting.

Example 4 ointment

The embodiment provides a Tibetan medicine composition, which comprises the following raw materials: 40g of curcuma longa, 10.5g of nutmeg, 25g of nardostachys chinensis, 10.2g of actinolite, 20g of liquorice, 0.1g of artificial musk, 30g of dried ginger, 25.5g of caraway, 20g of acorus calamus, 10.3g of pepper and 15.5g of trona.

The ointment of the Tibetan medicine composition comprises the following components in percentage by mass of 4000 g: 40g of curcuma longa, 10g of nutmeg, 25g of rhizoma nardostachyos, 10g of actinolite, 20g of liquorice, 0.1g of artificial musk, 30g of dried ginger, 25g of caraway, 20g of calamus, 10g of pepper, 15g of trona, 320g of liquid paraffin, 320g of glycerin, 80g of polysorbate 80, 8g of methylparaben and the balance of water.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona according to the above formula, pulverizing into coarse powder, mixing, and adding liquid paraffin, glycerol, polysorbate 80, methyl hydroxybenzoate and water. Stirring at 80 deg.C to make into paste, cooling to 38 deg.C, adding artificial Moschus, stirring to obtain 1000g ointment, standing at room temperature for 4 hr, and packaging.

EXAMPLE 5 ointment

The ointment of the Tibetan medicine composition comprises the following components in percentage by mass of 400 g: 36.3g of curcuma longa, 12.1g of nutmeg, 19.4g of nardostachys chinensis, 12.1g of actinolite, 17.0g of liquorice, 0.17g of artificial musk, 24.2g of dried ginger, 31.5g of caraway, 17.0g of calamus, 12.1g of pepper, 18.2g of trona, 20g of liquid paraffin, 20g of glycerol, 10g of polysorbate 10, 2g of methylparaben and the balance of water.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona according to the above formula, pulverizing into coarse powder, mixing, and adding liquid paraffin, glycerol, polysorbate 80, methyl hydroxybenzoate and water. Stirring at 80 deg.C to make into paste, cooling to 38 deg.C, adding artificial Moschus, stirring to obtain 1000g ointment, standing at room temperature for 5 hr, and packaging.

EXAMPLE 6 gels

The gel of the Tibetan medicine composition comprises the following components in percentage by mass of 1000 g: 36.3g of curcuma longa, 12.1g of nutmeg, 19.4g of nardostachys chinensis, 12.1g of actinolite, 17.0g of liquorice, 0.17g of artificial musk, 24.2g of dried ginger, 31.5g of caraway, 17.0g of calamus, 12.1g of pepper, 18.2g of trona, 94010.0 g of carbomer, 30g of glycerol, 2.0g of methylparaben, 3.0g of polysorbate 80 and the balance of water.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona according to the above formula, pulverizing into coarse powder, and mixing to obtain medicinal powder. Adding 200g of water into carbomer 940, swelling at 70 deg.C overnight, adding glycerol, methyl hydroxybenzoate, polysorbate 80 and medicinal powder, stirring to obtain gel, adding artificial Moschus and water, stirring to obtain 1000g of gel, and packaging.

Example 7 emplastrum

The emplastrum of the Tibetan medicine composition comprises the following components: 36.3g of curcuma longa, 12.1g of nutmeg, 19.4g of nardostachys chinensis, 12.1g of actinolite, 17.0g of liquorice, 0.17g of artificial musk, 24.2g of dried ginger, 31.5g of caraway, 17.0g of calamus, 12.1g of pepper, 18.2g of trona, 30g of rubber, 50g of rosin and 40g of zinc oxide.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona according to the above formula, decocting with water for 2 times, 8 times of water for 2 hr for the first time, 6 times of water for 1 hr for the second time, mixing filtrates, concentrating to density of 1.15-1.25g/cm³Clear paste (45 +/-2 ℃). Soaking rubber, Colophonium, and zinc oxide in ethanol, stirring, recovering ethanol to obtain a paste, adding the fluid extract into the paste, coating on non-woven fabric backing, and packaging to obtain 1000 plasters.

EXAMPLE 8 Aerosol preparation

The aerosol of the Tibetan medicine composition comprises: 36.3g of curcuma longa, 12.1g of nutmeg, 19.4g of nardostachys chinensis, 12.1g of actinolite, 17.0g of liquorice, 0.17g of artificial musk, 24.2g of dried ginger, 31.5g of caraway, 17.0g of calamus, 12.1g of pepper, 18.2g of trona, 2.0g of methylparaben, 8020.0 g of polysorbate and 100g of ethanol.

The preparation method comprises the following steps: weighing Curcuma rhizome, semen Myristicae, radix Et rhizoma Nardostachyos, Actinolitum, Glycyrrhrizae radix, Zingiberis rhizoma, fructus Cari Carvi, rhizoma Acori Calami, fructus Zanthoxyli and trona according to the above formula, percolating with 10 times of ethanol, recovering ethanol from percolate, and concentrating to density of 1.05-1.10g/cm³Clear paste (30 +/-2 ℃). Mixing the fluid extract, methyl hydroxybenzoate, polysorbate 80 and ethanol, filtering, adding water to 1000ml, and filtering again. Subpackaging into bottle with spray valve to obtain the final product.

Experimental example 1

1. Experimental animals: male (Lepr) ko/ko genotype mice were model mice, SPF grade, 8 weeks old, 35-55g in weight, 80. Male (Lepr) wt/wt genotype mice served as control mice, SPF grade, 8 weeks old, 20-30g in weight, 10. The experimental animals are provided by Jiangsu Jiejiaokang biotechnology limited.

2. Preparation of test drugs

The ointment prepared in example 1 of the present invention was administered to test animals at the dose shown in Table 1 using the ointment base as a placebo.

Wherein the ointment matrix used in the placebo group is prepared by taking 80g of liquid paraffin, 80g of glycerin, 10g of polysorbate 80, 10g of methyl hydroxybenzoate and 628g of water, stirring at 80 ℃ to prepare an ointment, and standing at room temperature for 4.5 hours.

Table 1 experimental dose design

	Dosage to be administered	Area of administration (cm)²)
			Test drug Low dose group	0.1g crude drug/kg animal body weight	0.5×0.5
Test drug medium dose group	0.3g crude drug/kg animal body weight	0.5×1.5
			High dose group of test drugs	0.9g crude drug/kg animal body weight	1.5×1.5
Placebo group (model control group)	0g crude drug/kg animal body weight	1.5×1.5

3. Experimental methods

(1) The administration method comprises the following steps: a diabetic peripheral neuropathy model was naturally developed using male (Lepr) ko/ko genotype db/db mice, and the effect of different doses of the test agent on peripheral neuropathy was observed. Male (Lepr) wt/wt genotype mice were used as normal controls. Animals freely ingest food and water, (Lepr) ko/ko genotype mice, after hyperglycemia occurs, measure MCV, SCV and blood glucose once a week, when MCV shows obvious conduction velocity reduction, model mice are randomly and evenly divided into 5 groups according to MCV, pain threshold and blood glucose, wherein the groups are respectively a model control group, a test drug group (a low dose group, a medium dose group and a high dose group) and a positive drug group, and each group comprises 10 mice. The thigh of the mouse is shaved, the placebo and the tested drugs are respectively smeared on the sciatic nerve part of the leg of the mouse in the model control group and the test drug group, the application thickness of each dose group is consistent, the area is shown in the table, and the administration period is 8 weeks. Wherein the dosage of the low dose group is 0.1g crude drug/kg animal body weight, the dosage of the medium dose group is 0.3g crude drug/kg animal body weight, the dosage of the high dose group is 0.9g crude drug/kg animal body weight, and the model control group is administered with ointment matrix with the same volume as the high dose group. The positive drug group had a mecobalamin solution (solvent is distilled water, mass concentration is 0.015mg/ml) intragastrically once a day, intragastrically volume: 20mL/kg animal body weight, administration cycle 8 weeks.

(2) Testing of pain threshold

And placing each group of mice on a suspended iron wire grid in a transparent glass observation box for free movement, after combing and exploring movements of the mice basically disappear, vertically stimulating the bottoms of the feet of the mice by using standardized fiber yarns for 5 seconds, and recording the stimulation strength of the mice after stimulation when the mice quickly contract or lick the feet. The measurement is carried out 3 times, each time interval (3-5) min, 3 average values are taken as the pain threshold of the mouse, and the measurement is carried out once every two weeks during grouping and after administration.

(3) Testing of motor nerve conduction velocity

The measurement is carried out by adopting an electronic stimulator and a physiological signal data acquisition system. The mouse is anesthetized and fixed on a mouse plate, the left hind leg is straightened and fixed, a stimulating electrode is inserted into the left ischial incisal track, a recording electrode is placed at the ankle joint, a reference electrode is placed between the stimulating electrode and the recording electrode, and all electrodes are needle electrodes in the test. The method is characterized in that square wave stimulation is adopted, the wave width is 1ms, the interval between every two stimulations is 5s, the latency period is recorded, namely the time from the stimulation of a stimulation electrode to the appearance of the potential of muscle, each rat measures the third order wave to obtain an average value, the length between the stimulation electrode and a recording electrode is measured by a vernier caliper to serve as the conduction distance, and MCV is the motor nerve conduction distance/latency period. The measurements were made at the time of grouping and every two weeks after administration.

4. Results of the experiment

(1) Effect on pain threshold in spontaneously diabetic mice

Before administration, the pain threshold of the mice in the model control group is obviously higher than that of the mice in the normal control group (2.3 +/-0.6 vs1.1 +/-0.2 g, and P is less than 0.001), which indicates that the spontaneous diabetic mice generate hypoalgesia. No significant difference (P >0.05) was observed between each administration group and the model control group, and the results are shown in Table 2.

After the administration is carried out for 2-8 weeks, compared with a normal control group, the pain threshold of the model control group is always obviously higher than that of the normal control group (P < 0.01-0.001). Compared with a model control group, the pain threshold of a model mouse can be reduced to different degrees (P is less than 0.05-0.001) by 0.1, 0.3 and 0.9g of the test drug/kg after the administration for 2-8 weeks; after administration for 2-8 weeks, the positive drug mecobalamin 0.3mg/kg can lower the pain threshold of model mice to different degrees (P < 0.05-0.001), and the results are shown in Table 2.

Compared with the model control group, the administration period of the test drug is 4-8 weeks, and 0.9g of the test drug/kg of the test drug can reduce the pain threshold of the model mouse to different degrees (P is less than 0.05). After administration (4-8 weeks), the positive drug mecobalamin 0.3mg/kg can lower the pain threshold of model mice to different degrees (P <0.05), and the results are shown in Table 3.

TABLE 2 Effect of test drugs on pain threshold in spontaneously diabetic mice: (

n＝10)

Compared with the normal control group,^△△P<0.01，^△△△P<0.001; p compared to model control group<0.05，**P<0.01，***P<0.001; n: number of samples.

TABLE 3 Effect of test drugs on threshold Difference in spontaneous diabetic mice: (

n＝10)

P <0.01 compared to model control group; n: number of samples.

Through analysis, the following results are obtained: the test drug can reduce the pain threshold of the model mouse, and the drug effect has no significant difference with mecobalamin, which shows that the test drug can improve the sensitivity of the nerve ending of the diabetic model mouse with neuropathy. Therefore, the symptoms of numbness of limbs of the diabetic peripheral neuropathy patients can be relieved.

(2) Influence result on motor nerve conduction velocity of mice with peripheral neuropathy caused by spontaneous diabetes

Before administration, the motor nerve conduction velocity of the model control group mice is significantly lower than that of the normal control group (4.29 +/-0.67 vs5.90 +/-1.18 m/s, P < 0.01;). No significant difference (P >0.05) was observed between each of the administered groups and the model control group, and the results are shown in Table 4.

After the administration for 2-8 weeks, compared with a normal control group, the motor nerve conduction velocity of the mice in the model control group is always remarkably higher than that in the normal control group (P < 0.05-0.001). Compared with the model control group, the test drug 0.3g and 0.9g crude drug/kg can improve the motor nerve conduction velocity of the model mouse to different degrees (P is less than 0.05-0.001) after administration for 4-8 weeks; after the administration for 6-8 weeks, the positive drug mecobalamin 0.3mg/kg can improve the motor nerve conduction velocity of the model mouse to different degrees (P is less than 0.05-0.01), and the results are shown in Table 4.

Compared with the model control group, the difference value of the test drug and the drug before administration is compared, the test drug 0.9g crude drug/kg can improve the motor nerve conduction velocity of the model mouse to different degrees (P <0.05) after administration for 4-8 weeks. After the administration for 4-8 weeks, the positive drug mecobalamin 0.3mg/kg can improve the motor nerve conduction velocity of the model mouse to different degrees (P <0.05), and the results are shown in Table 5.

Table 4 effect on MCV in spontaneously diabetic mice: (

n＝10)

Compared with the normal control group,^△P<0.05，^△△P<0.01，^△△△P<0.001; p compared to model control group<0.05，**P<0.01，***P<0.001; n: number of samples.

Table 5 effect on MCV differential in spontaneously diabetic mice: (

n＝10)

Compared with the model control group,^*P<0.05; n: number of samples.

And (4) conclusion: a spontaneous diabetic peripheral neuropathy mouse model is adopted, and test drugs 0.1, 0.3 and 0.9g of crude drugs/kg are continuously administered for 2-8 weeks, so that the pain threshold and the sciatic nerve motor nerve conduction speed of the model mouse can be improved to different degrees, and the result shows that the test drugs can relieve the sensory disturbance of the diabetic model mouse by improving the sciatic nerve motor conduction speed of the diabetic mouse.

It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims

1. The application of a Tibetan medicine composition in preparing a medicine for preventing and/or treating diabetic peripheral neuropathy is characterized in that the Tibetan medicine composition comprises the following raw material medicines: turmeric, nutmeg, nardostachys chinensis, actinolite, licorice, artificial musk, dried ginger, caraway, calamus, zanthoxylum and trona.

2. The use of claim 1, wherein the diabetic peripheral neuropathy is caused by diabetic peripheral nerve injury.

3. The use according to claim 1 or 2, wherein the Tibetan medicinal composition comprises the following raw material medicines in parts by weight: 30-40 parts of turmeric, 10-15 parts of nutmeg, 15-25 parts of nardostachys chinensis, 10-15 parts of actinolite, 15-20 parts of liquorice, 0.1-0.2 part of artificial musk, 20-30 parts of dried ginger, 25-35 parts of caraway, 15-20 parts of acorus calamus, 10-15 parts of pepper and 15-20 parts of trona.

4. The use of any one of claims 1-3, wherein the Tibetan medicinal composition is prepared by pulverizing and mixing the raw materials, or extracting the raw materials by a conventional extraction method after mixing, or mixing the extracts obtained by extracting the raw materials respectively.

5. The use of any of claims 1-4, wherein the Tibetan medicinal composition is processed into the conventional pharmaceutical preparation in the field by the conventional preparation process, the pharmaceutical preparation is an oral dosage form or an external dosage form,

the oral preparation is selected from granules, pills, capsules, tablets or oral liquid, the external preparation is selected from ointment, emplastrum, aerosol, spray, wet dressing, lotion or gel, and the conventional preparation process comprises the steps of crushing, decocting, percolating, leaching, ultrasonic treatment or steam distillation of medicinal materials.

6. The use of claim 5, wherein the pharmaceutical formulation further comprises a pharmaceutically acceptable carrier; the pharmaceutically acceptable carrier is selected from at least one of pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adherents, integration agents, permeation enhancers, pH regulators, buffers, plasticizers, surfactants, thickeners, encapsulation agents, humectants, absorbents, diluents, flocculants, deflocculants, filter aids, release retardants, polymeric matrix materials, and film-forming materials.

7. The use of claim 5 or 6, wherein the pharmaceutical preparation is an ointment, the ointment further comprises an ointment base, and preferably, the mass ratio of the Tibetan medicine composition to the ointment base is 0.5: 9.5-5: 5.

8. the use according to claim 7, wherein the ointment base comprises polysorbate 80, liquid paraffin, glycerin, methylparaben and water, preferably, the mass ratio of polysorbate 80, liquid paraffin, glycerin, methylparaben and water is 1-10: 20-60: 20-60: 0.5-2: 200-400.

9. Use according to claim 7 or 8, characterized in that the ointment is prepared by a process comprising the following steps:

10. Use of a Tibetan medicinal composition or a pharmaceutical preparation as claimed in any of claims 1 to 9 for the manufacture of a medicament for use as:

(1) treating diabetic peripheral nerve injury, and increasing nerve conduction velocity;

(2) relieving abnormal sensation caused by diabetic peripheral nerve injury.