CN113633682B - Cream for treating herpes zoster and preparation method thereof - Google Patents

Abstract

The invention discloses an application of pulsatilla chinensis or an extract thereof in preparing a medicament for treating herpes zoster and a composition taking the pulsatilla chinensis extract as an active ingredient. The composition has no toxic or side effect on a human body, does not have adverse reaction and sequelae after being used by a patient, has an effect of treating herpes zoster obviously superior to that of acyclovir cream which is generally used clinically at present, is an externally-applied good medicine for treating herpes zoster of skin, avoids damage to gastrointestinal functions of the human body caused by oral administration of the medicine, achieves an obvious treatment effect, and has wide application value.

Description

Cream for treating herpes zoster and preparation method thereof

Technical Field

The invention belongs to the field of medicines, and particularly relates to a cream for treating herpes zoster and a preparation method thereof.

Background

Herpes zoster (herpes zoster) is a common acute mucocutaneous disease caused by Varicella Zoster Virus (VZV). After most patients are infected with varicella-zoster virus, the varicella-zoster virus firstly shows moist erythema, then develops into papule-soybean papule-like papule, is distributed in a cluster shape without fusion, then quickly becomes blister, the blister wall is tense and shiny, the blister liquid is clear, the periphery is surrounded by ruddy halo, and simultaneously, the symptoms of fever, hypodynamia, anorexia and the like are accompanied; the course of the disease is 2-3 weeks, the disease does not relapse after the disease is treated, and the immunity can be performed for the whole life. Some patients become virus-carrying patients after being infected without symptoms, because the virus has neurotropic property, the virus can be latent in neurons of spinal nerve heel ganglia for a long time after being infected, when the infected patients have low resistance or are tired and catch a cold, the virus can grow and propagate again and move to the skin along nerve fibers, so that the affected nerves and the skin generate strong inflammation, and the nerve pain and itching are accompanied with strong pain and itching, especially for old patients.

The incidence rate of herpes zoster is 0.14-0.48%, the difference of regions and ethnicities is not large, and the number of the middle-aged and the elderly is large. It is caused by lack of exercise, staying up all night, fatigue, mental stimulation, low immunity and resistance (leukemia, lymphoma, AIDS, systemic lupus erythematosus, etc.), local trauma, acute and chronic infectious diseases (cold, infectious hepatitis, tuberculosis, etc.), nervous system diseases (epidemic meningitis, myelitis, epilepsy, tuberculous meningitis, sciatica, etc.), operation, chemical or drug poisoning, malignant tumor, weakness after illness, etc. Every person has an incidence of 15-20% in a lifetime, the incidence is frequent in spring and autumn, the incidence is rarely caused in children (chickenpox is generated in children), adults are frequent, the incidence increases with the age after the age of 12 years, the incidence is stable to 0.3% after the age of 20-50 years, the incidence is 0.5% above the age of 50 years, the incidence is 0.7% above the age of 60 years, but no obvious gender distinction exists, the traditional Chinese medicine composition is a common disease and frequently-occurring disease of middle-aged and old people, the harm is extremely high, and the incidence shows a trend of increasing year by year.

At present, western medicine treatment for the disease comprises means such as medicine application and nerve block, wherein the medicine application comprises antiviral acyclovir, valaciclovir and famciclovir, the medicine can not radically cure neuralgia sequelae, neuralgia medicines such as paroxetine, fluvoxamine, carbamazepine, oxycodone and the like are also needed for treatment, and the nerve block means is adopted for severe pain. Although the methods are usually oral or invasive, the methods are effective, but the method is long in time, large in side effect of oral medicines, or unnecessary pain caused by invasive operation, high in economic burden and more in sequelae, so that natural effective medicines are searched, prepared into aqua or ointment and externally applied to affected parts to quickly and effectively prevent the spread of herpes zoster, and the herpes caused by herpes zoster virus is very necessary to be repaired efficiently in a short time.

Patent CN103479820A discloses a Chinese patent medicine for treating herpes zoster, which contains 8 kinds of medicinal flavors such as Chinese pulsatilla root, and has the disadvantages of many medicinal flavors, high cost, undefined preparation method, uncertain curative effect and unsuitability for clinical popularization and application.

Disclosure of Invention

The invention aims to provide application of pulsatilla chinensis or an extract thereof in preparing a medicament for treating herpes zoster.

Further, the extract is an ethanol extract.

Furthermore, the concentration of the ethanol is 50-80%.

Further, the medicament is an external preparation.

The invention also provides a composition for treating herpes zoster, which is an external preparation prepared from the following raw materials in parts by weight:

8-12 parts of stearic acid, 4-6 parts of vaseline, 1-3 parts of lanolin, 8-10 parts of glyceryl monostearate, 8-12 parts of glycerol, 4-8 parts of triethanolamine, 0.1-0.3 part of ethylparaben and 8-12 parts of a pulsatilla extract.

Further, the external preparation is prepared from the following raw materials in parts by weight:

10 parts of stearic acid, 5 parts of vaseline, 2 parts of lanolin, 9 parts of glyceryl monostearate, 10 parts of glycerol, 6 parts of triethanolamine, 0.2 part of ethylparaben and 10 parts of a pulsatilla extract.

Further, the preparation method of the pulsatilla chinensis extract comprises the following steps: extracting Pulsatilla chinensis with ethanol solution, filtering, concentrating the filtrate, dissolving in water, passing through resin, collecting ethanol eluate, and concentrating to obtain soft extract.

Further, the Chinese pulsatilla root extract is thick paste obtained by reflux extraction of Chinese pulsatilla root by adding 50-80% ethanol solution, filtration, concentration of filtrate to relative density of 1.00-1.20 at 60 ℃, dissolution by adding water, passing through AB-8 resin, collection of 30-60% ethanol eluent and concentration.

Further, the preparation is a water agent, an emulsion, a cream, an ointment, a film agent or a gel.

The invention finally provides a process for preparing the aforementioned composition, characterized in that: the method comprises the following steps:

(1) preparing an oil phase: taking stearic acid, vaseline, lanoline and glyceryl monostearate according to the formula ratio, heating to 80 ℃, melting into an oil phase, and stirring uniformly to obtain the oil phase;

(2) preparation of an aqueous phase: heating glycerol, triethanolamine and ethylparaben to 80 deg.C to dissolve into water phase, and stirring to obtain water phase;

(3) slowly adding the water phase into the oil phase under stirring, homogenizing and emulsifying at 80 deg.C for 5min, removing heating, stirring until the temperature is reduced to below 60 deg.C, adding radix Pulsatillae extract, stirring, adding water to desired volume, stirring, and cooling.

The composition for treating herpes zoster takes the pulsatilla chinensis bunge alcohol extract as an active ingredient, is low in price and convenient to use, and is proved by experiments to have no toxic or side effect on a human body, no adverse reaction and sequelae after the composition is used by a patient, the effect of treating herpes zoster is obviously superior to that of acyclovir cream which is generally used clinically at present, the composition is an externally-used good medicine for treating the herpes zoster of skin, the damage to the gastrointestinal function of the human body caused by oral medicines is avoided, the obvious treatment effect is achieved, and the composition has wide application value.

Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Detailed Description

EXAMPLE 1 preparation of a composition according to the invention

(1) Extract of Chinese pulsatilla root: extracting radix Pulsatillae with 8 times of v/w, ml/g 70% ethanol under reflux for 3 times, each for 2 hr, mixing extractive solutions, filtering, concentrating the filtrate to relative density of 1.05-1.10 at 60 deg.C, dissolving the filtrate with water, passing through AB-8 resin, eluting with 50% ethanol, and concentrating the eluate under reduced pressure to relative density of 1.20 at 60 deg.C to obtain soft extract.

(2) Oil phase: heating 8g of stearic acid, 4g of vaseline, 1g of lanolin and 8g of glyceryl monostearate to 80 ℃ to melt into an oil phase, stirring uniformly, and keeping the temperature for later use.

(3) Water phase: heating 8g of glycerol, 4g of triethanolamine and 0.1g of ethylparaben to 80 ℃ to dissolve into a water phase, stirring uniformly, and standing for later use.

(4) Slowly adding the water phase into the oil phase under stirring, keeping the temperature at 80 deg.C, homogenizing and emulsifying for 5min, removing heating, continuously stirring until the temperature is reduced to below 60 deg.C, adding radix Pulsatillae extract 8g, stirring, adding water to constant volume of 100mL, stirring, naturally cooling, vacuumizing, and canning.

Example 2 preparation of a composition according to the invention

(1) Extract of Chinese pulsatilla root: reflux-extracting radix Pulsatillae with 10 times of 70% ethanol for 3 times, each for 2 hr, mixing extractive solutions, filtering, concentrating the filtrate to relative density of 1.05-1.10 at 60 deg.C, dissolving the filtrate with water, passing through AB-8 resin, eluting with 50% ethanol, and concentrating the eluate under reduced pressure to relative density of 1.20 at 60 deg.C to obtain soft extract.

(2) Oil phase: heating 10g of stearic acid, 5g of vaseline, 2g of lanolin and 9g of glyceryl monostearate to 80 ℃ to melt into an oil phase, stirring uniformly, and keeping the temperature for later use.

(3) Water phase: 10g of glycerol, 6g of triethanolamine and 0.2g of ethylparaben, heating to 80 ℃ to dissolve the glycerol, the triethanolamine and the ethylparaben into a water phase, stirring the water phase uniformly, and standing for later use.

(4) Slowly adding the water phase into the oil phase under stirring, maintaining the temperature at 80 deg.C, homogenizing and emulsifying for 5min, removing heating, stirring until the temperature is reduced to below 60 deg.C, adding radix Pulsatillae extract 10g, stirring, adding water to desired volume of 100mL, stirring, naturally cooling, vacuumizing, and canning.

EXAMPLE 3 preparation of the composition of the invention

(1) Extract of pulsatilla chinensis regel: reflux-extracting radix Pulsatillae with 12 times of 70% ethanol for 3 times, each for 2 hr, mixing extractive solutions, filtering, concentrating the filtrate to relative density of 1.05-1.10 at 60 deg.C, dissolving the filtrate with water, passing through AB-8 resin, eluting with 50% ethanol, and concentrating the eluate under reduced pressure to relative density of 1.20 at 60 deg.C.

(2) Oil phase: 12g of stearic acid, 6g of vaseline, 3g of lanolin and 10g of glyceryl monostearate, heating to 80 ℃, melting into an oil phase, stirring uniformly, and keeping the temperature for later use.

(3) Water phase: heating 12g of glycerol, 8g of triethanolamine and 0.3g of ethylparaben to 80 ℃ to dissolve into a water phase, stirring uniformly, and standing for later use.

(4) Slowly adding the water phase into the oil phase under stirring, maintaining the temperature at 80 deg.C, homogenizing and emulsifying for 5min, removing heating, stirring until the temperature is reduced to below 60 deg.C, adding radix Pulsatillae extract 12g, stirring, adding water to desired volume of 100mL, stirring, naturally cooling, vacuumizing, and canning.

EXAMPLE 4 preparation of the composition of the invention

(1) Extract of Chinese pulsatilla root: reflux-extracting radix Pulsatillae with 10 times of 70% ethanol for 2 times, each for 1 hr, mixing extractive solutions, filtering, concentrating the filtrate to relative density of 1.05-1.10 at 60 deg.C, dissolving the filtrate with water, passing through AB-8 resin, eluting with 50% ethanol, and concentrating the eluate under reduced pressure to relative density of 1.20 at 60 deg.C to obtain soft extract.

(2) Oil phase: heating 10g of stearic acid, 5g of vaseline, 2g of lanolin and 9g of glyceryl monostearate to 80 ℃ to melt into an oil phase, stirring uniformly, and keeping the temperature for later use.

(3) Water phase: 10g of glycerol, 6g of triethanolamine and 0.2g of ethylparaben, heating to 80 ℃ to dissolve the glycerol, the triethanolamine and the ethylparaben into a water phase, stirring the water phase uniformly, and standing for later use.

(4) Slowly adding the water phase into the oil phase under stirring, maintaining the temperature at 80 deg.C, homogenizing and emulsifying for 5min, removing heating, stirring until the temperature is reduced to below 60 deg.C, adding radix Pulsatillae extract 10g, stirring, adding water to desired volume of 100mL, stirring, naturally cooling, vacuumizing, and canning.

The beneficial effects of the invention are illustrated by way of test examples below:

test example 1 toxicity test

1. Test animal

Selecting 50 healthy mice with the weight of 18-22 g, randomly dividing the mice into 5 groups, wherein each group comprises 10 mice, and the 1 st group is a blank control group; the creams prepared in examples 1 to 4 were tried in groups 2 to 5.

2. Method of producing a composite material

Depilating 2-5 groups of mice with depilating area of 3cm × 3cm, and applying 3g of cream on the depilatingHair part, twice daily. Observing for 20 days, the white mice survive healthily without any toxic and side effect, dissecting and observing the tissue state of each organ, calculating the organ coefficient, and detecting the blood biochemical index, wherein the organ coefficient (%) is the wet weight of the organ/body weight multiplied by 100%. Analyzing experimental data by SPSS 23.0 statistical software, and measuring data

The mean comparison of samples among multiple groups adopts one-factor analysis of variance, and the difference with P less than 0.05 has statistical significance.

3. Results

The main organs of heart, liver, spleen, lung and kidney of each group of mice are not abnormal by naked eyes, and specific results are shown in tables 1-2. As can be seen from Table 1, the weight and organ coefficient of the test group were not different (P > 0.05) compared with the white mice of the blank control group; as can be seen from Table 2, compared with the blank control group of white mice, the biochemical blood index of each test group of mice has no difference (P is more than 0.05), which indicates that the cream provided by the invention has no obvious influence on the biochemical blood index in the treatment process. Experiments prove that the cream for treating herpes zoster provided by the invention is externally used and nontoxic.

TABLE 1 body weight and organ index of mice in each group

TABLE 2 Biochemical index of blood of each group of mice

Group of	Blank control group	Example 1	Example 2	Example 3	Example 4
						GLU(mmol/L)	6.78±0.83	7.54±0.54	5.85±0.68	6.57±0.76	7.78±0.64
TP(g/L)	62.34±3.17	61.73±4.26	64.28±2.74	63.56±3.25	62.87±2.56
						ALB(g/L)	30.47±2.84	32.63±1.43	29.72±2.49	31.64±1.87	28.86±3.16
ALKP(U/L)	163.13±36.71	152.49±48.57	158.65±39.87	175.79±28.96	167.24±32.18
						GOT(U/L)	120.15±5.86	128.84±8.79	117.57±5.74	113.24±4.86	126.27±6.49
GPT(U/L)	68.47±15.75	75.27±10.57	63.45±13.74	65.48±14.85	70.95±14.43
						CREA(μmol/L)	65.14±3.54	63.28±2.74	60.96±3.19	62.72±4.15	67.42±2.41

Note: GLU-blood glucose, TP-total protein, ALB-albumin, ALKP-alkaline phosphatase, GOT-glutamic oxaloacetic transaminase, GPT-glutamic pyruvic transaminase, GREA-creatinine.

Test example 2 evaluation of trial Effect of cream for treating herpes zoster

1. Source of study

200 patients with herpes zoster of 25-60 years of age were recruited (male to female ratio 1: 1). The clinical symptoms of patients are manifested by symptoms of different degrees of muscular pain and numbness, fever, hypodynamia, malaise, inappetence, swelling and pain of local lymph nodes, burning skin of affected parts, hyperesthesia or neuralgia, irregular erythema, clustered blisters and the like.

2. Method of producing a composite material

Dividing the patients into 5 groups, each group comprises 40 patients, the first group is a control group, applying acyclovir cream, the second group to the fifth group are test groups, applying the creams prepared in the examples 1 to 4 respectively, 3g each time, once every morning and evening, uniformly applying the creams to the pain part, 7 days is a treatment course, continuously using 2 treatment courses, comprehensively comparing the treatment effect, analyzing the experimental data by SPSS 23.0 statistical software, and measuring the data to obtain the final product

Indicating, column t test, count data column χ ² And (6) checking.

The therapeutic effect evaluation standard refers to the relevant standard in the Chinese medicine disease diagnosis therapeutic effect standard to evaluate the therapeutic effect. And (3) healing: the rash completely disappeared, the pain completely disappeared, and the clinical symptoms and signs disappeared. The method has the following advantages: the degree of rash regression was > 30%, pain was significantly reduced, mild pain was still present, and some of the clinical signs were gone. And (4) invalidation: the degree of rash regression was < 30% and even worsened with no significant reduction or increase in pain. The cure rate and the effective rate are combined to be the total effective rate.

In addition, statistical comparisons of observations were made of the patients' blister time, pain relief time, and crusting time.

3. Results

The specific results are shown in tables 3-4.

TABLE 3 trial effect of cream for treatment of herpes zoster Table

Group of	Number of examples	Recovery method	Is effective	Invalidation	Total effective rate (%)
						Control group	40	14	15	11	72.5
Example 1	40	18	18	4	90.0*
						Example 2	40	22	15	3	92.5*
Example 3	40	20	16	4	90.0*
						Example 4	40	16	18	6	85.0*

Note: p < 0.05 compared to control.

It can be seen from table 3 that the total effective rates of examples 1 to 4 are all higher than those of the control group, and compared with the control group, the difference has statistical significance (P is less than 0.05), wherein the total effective rate of example 2 can reach 92.5%. Therefore, on the whole, the cream for treating herpes zoster prepared in the embodiments 1 to 4 of the invention has better treatment effect than acyclovir cream, and can improve the disease cure rate.

Table 4 comparison of time to clinical symptom improvement (d,

)

group of	Number of effective cases	Blister stopping time	Time to pain relief	Time to scab
					Control group	29	3.46±1.13	6.62±1.65	9.14±3.16
Example 1	36	1.86±0.54*	3.48±1.14*	6.78±1.13*
					Example 2	37	1.75±0.81*	3.25±0.61*	6.23±2.41*
Example 3	36	1.94±0.95*	3.61±0.78*	6.41±2.67*
					Example 4	34	2.12±0.47*	4.17±0.84*	7.27±3.24*

Note: p < 0.05 compared to control.

As can be seen from table 4: after treatment, patients of examples 1-4 had a shorter blister time, pain relief time, and scab formation time than the control group, with statistical differences (P < 0.05), with the shortest time in example 2. Therefore, the cream for treating herpes zoster, which is prepared in the embodiments 1 to 4 of the invention, can quickly diminish inflammation and relieve pain, shorten the course of disease, effectively improve the clinical symptoms of patients, relieve pain and improve the life of the patients

In conclusion, the composition has no toxic or side effect on a human body, no adverse reaction and sequelae after the composition is used by a patient, has an effect of treating herpes zoster obviously superior to that of acyclovir cream which is clinically and generally used at present, is an external good medicine for treating herpes zoster of skin, and has wide application value.

Claims (5)

1. Use of Pulsatillae radix extract in preparing medicine for treating herpes zoster;

the radix Pulsatillae extract is prepared by reflux-extracting radix Pulsatillae with 70% ethanol solution, filtering, concentrating the filtrate to relative density of 1.00-1.20 at 60 deg.C, dissolving in water, passing through AB-8 resin, collecting 50% ethanol eluate, and concentrating to obtain soft extract;

the medicine is an external preparation.

2. A composition for treating herpes zoster, comprising: the external preparation is prepared from the following raw materials in parts by weight:

8-12 parts of stearic acid, 4-6 parts of vaseline, 1-3 parts of lanolin, 8-10 parts of glyceryl monostearate, 8-12 parts of glycerol, 4-8 parts of triethanolamine, 0.1-0.3 part of ethylparaben and 8-12 parts of a pulsatilla root extract;

the radix Pulsatillae extract is prepared by reflux-extracting radix Pulsatillae with 70% ethanol solution, filtering, concentrating the filtrate to relative density of 1.00-1.20 at 60 deg.C, dissolving in water, passing through AB-8 resin, collecting 50% ethanol eluate, and concentrating to obtain soft extract.

3. The composition of claim 2, wherein: the external preparation is prepared from the following raw materials in parts by weight:

10 parts of stearic acid, 5 parts of vaseline, 2 parts of lanolin, 9 parts of glyceryl monostearate, 10 parts of glycerol, 6 parts of triethanolamine, 0.2 part of ethylparaben and 10 parts of a pulsatilla extract.

4. The composition according to claim 2 or 3, characterized in that: the preparation is aqua, emulsion, cream, ointment, film or gel.

5. A process for preparing the composition of any one of claims 2 to 4, characterized in that: it comprises the following steps:

(1) preparing an oil phase: taking stearic acid, vaseline, lanoline and glyceryl monostearate according to the formula ratio, heating to 80 ℃, melting into an oil phase, and stirring uniformly to obtain the oil phase;

(2) preparation of an aqueous phase: heating glycerol, triethanolamine and ethylparaben to 80 deg.C to dissolve into water phase, and stirring to obtain water phase;

(3) slowly adding the water phase into the oil phase under stirring, homogenizing and emulsifying at 80 deg.C for 5min, removing heating, stirring until the temperature is reduced to below 60 deg.C, adding radix Pulsatillae extract, stirring, adding water to desired volume, stirring, and cooling.