Traditional Chinese medicine ointment for treating herpes zoster through external application as well as preparation method and application of traditional Chinese medicine ointment

Abstract

The invention provides a traditional Chinese medicine ointment for treating herpes zoster through external application as well as a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The traditional Chinese medicine ointment for treating herpes zoster through external application comprises astragalus membranaceus, Indian kalimeris herb, liquorice, snake slough, needle sand, realgar, flax ash and mature vinegar. Wherein the radix astragali is used as a monarch drug for tonifying qi, drawing toxin and promoting tissue regeneration; the realgar is used for detoxifying, resisting inflammation and easing pain, and is a ministerial drug; the snake slough has the effects of dispelling wind and arresting itching, astringing and promoting tissue regeneration, the needle sand has the effects of astringing and drying dampness, and the flax ash has the effects of astringing And the mature vinegar is used for regulating, activating blood and promoting permeation, and is used as a conductant drug. All the medicines are combined to achieve the effects of resisting viruses, diminishing inflammation, relieving pain and repairing, and have a remarkable effect on treating herpes zoster. Animal experiment results show that the traditional Chinese medicine ointment can relieve central hyperalgesia and peripheral nervous system injury caused by varicella-zoster virus.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine ointment for external application to treat herpes zoster, and a preparation method and application thereof. Background Art

[0002] Herpes zoster is an acute inflammatory skin disease caused by the varicella-zoster virus. The virus is neurotropic and can remain dormant in the neurons of the dorsal root ganglia of the spinal cord for a long time after infection. When the body's resistance is reduced, the virus can grow and multiply again and move along the nerve fibers to the skin, causing severe inflammation of the invaded nerves and skin. Its main symptoms are clustered blisters distributed along the nerves, accompanied by obvious neuralgia, which seriously affects the patient's quality of life.

[0003] At present, there are many clinical treatments for herpes zoster. Western medicine mostly uses antiviral drugs, such as acyclovir and ganciclovir. Although these drugs can inhibit viral replication and alleviate symptoms to a certain extent, they have adverse reactions, such as nausea, vomiting, diarrhea, etc., and long-term use may also lead to drug resistance. At the same time, for some patients, the use of antiviral drugs alone is difficult to effectively relieve the symptoms of neuralgia. Hormonal drugs such as dexamethasone and prednisolone have a certain effect in reducing inflammatory responses, but long-term or improper use will bring serious side effects such as decreased immunity, increased blood sugar, osteoporosis, and easy recurrence.

[0004] In the field of traditional Chinese medicine, external treatment is considered an important supplement to the treatment of herpes zoster because of its direct access to the diseased area and few side effects. Traditional Chinese medicine external application often uses drugs such as realgar, phellodendron, and borneol to clear away heat and detoxify, promote blood circulation and relieve pain, and inhibit viral replication and relieve inflammation and pain through local penetration. However, existing Chinese medicine external application preparations have the following problems: First, the formula compatibility and dosage are not optimized, and some medicinal materials are highly irritating and easy to cause skin allergies; second, traditional preparation processes (such as decoction and concentration or coarse powder paste) are difficult to effectively extract active ingredients (such as terpenoid compounds), resulting in low bioavailability; third, the dosage form has poor stability, affecting efficacy and safety.

[0005] Therefore, there is an urgent need to develop a Chinese medicine compound ointment with scientific formulation, standardized preparation process, and antiviral, anti-inflammatory and analgesic effects to make up for the shortcomings of existing therapies and improve patient compliance and treatment safety. Summary of the invention

[0006] The object of the present invention is to provide a traditional Chinese medicine ointment for external application to treat herpes zoster, a preparation method and an application thereof. The traditional Chinese medicine ointment provided by the present invention has antiviral, anti-inflammatory and analgesic effects, can effectively treat herpes zoster, relieve postherpetic neuralgia and promote the healing of herpes.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] The invention provides a traditional Chinese medicine ointment for external application to treat herpes zoster, comprising the following raw materials in parts by weight: 15-25 parts of astragalus, 10-20 parts of amaranth, 8-12 parts of liquorice, 5-8 parts of snake skin, 1-3 parts of needle sand, 1-3 parts of realgar, 3-5 parts of sesame ash, 30-50 parts of aged vinegar and 10-15 parts of auxiliary materials.

[0009] Preferably, the auxiliary material is one or both of white vaseline and honey.

[0010] Preferably, the aging time of the aged vinegar is 3 years or more.

[0011] Preferably, the flax ash is obtained by calcining flax ash at 700-800° C. for 1-2 hours.

[0012] The invention provides a preparation method of the above-mentioned traditional Chinese medicine ointment, comprising: extracting astragalus through pulse electric field to obtain astragalus extract; extracting amaranth and licorice through ethanol ultrasonic method to obtain amaranth-licorice extract; performing ultrasonic enzymolysis on snake exuviae through composite enzyme to obtain snake exuviae extract; and mixing the astragalus extract, amaranth-licorice extract, snake exuviae extract, needle sand, realgar, sesame ash, aged vinegar and auxiliary materials to obtain the traditional Chinese medicine ointment.

[0013] Preferably, the solvent for the pulse electric field extraction is an ethanol solution with a volume percentage of 40%-50%, the solid-liquid ratio of the extracted astragalus and the solvent is 1:8-12 g / mL, the electric field strength is 10-15 kV / cm, the pulse width is 30-40 μs, the number of pulses is 5-10, the temperature is 30-40°C, and the time is 5-10 min.

[0014] Preferably, in the ethanol ultrasonic extraction, ethanol solution is used as the extraction solvent, the volume percentage of the ethanol solution is 80%-90%, the solid-liquid ratio of the total amount of Amaranthus and Licorice extracted by ultrasonic extraction and the solvent is 1:5-10g / mL, the extraction temperature is 60-70°C, the number of times is 1-3 times, and each time is 30-40min.

[0015] Preferably, the complex enzyme consists of keratinase and trypsin.

[0016] More preferably, the temperature of the ultrasonic enzymatic hydrolysis is 40-45°C, the pH value is 7.5-8.5, the power is 200-300W, the frequency is 40-50kHz, and the time is 30-40min.

[0017] The present invention also provides application of the above-mentioned traditional Chinese medicine ointment in preparing medicine for treating herpes zoster.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] The present invention provides a Chinese medicine ointment for external application to treat herpes zoster, comprising: astragalus, amaranth, liquorice, snake slough, needle sand, realgar, sesame ash, and aged vinegar. Astragalus invigorates qi, detoxifies and promotes tissue regeneration as the main medicine; amaranth clears away heat and detoxifies, cools blood and relieves swelling, and realgar detoxifies, resists inflammation and relieves pain as the ministerial medicine; snake slough dispels wind and stops itching, astringes and promotes tissue regeneration, needle sand astringes and dries dampness, and sesame ash astringes and resists bacteria as the adjuvant medicine; liquorice harmonizes various medicines, relieves urgency and relieves pain, and aged vinegar harmonizes, promotes blood circulation and promotes infiltration as the guiding medicine. The combination of various medicines has the effects of antiviral, anti-inflammatory, analgesic and repairing, and has a significant effect on the treatment of herpes zoster. Animal experimental results show that the Chinese medicine ointment of the present invention can significantly relieve pain reactions in the treatment of herpes zoster and relieve peripheral nervous system damage caused by varicella-zoster virus. DETAILED DESCRIPTION

[0020] The invention provides a traditional Chinese medicine ointment for external application to treat herpes zoster, comprising the following raw materials in parts by weight: 15-25 parts of astragalus, 10-20 parts of amaranth, 8-12 parts of liquorice, 5-8 parts of snake skin, 1-3 parts of needle sand, 1-3 parts of realgar, 3-5 parts of sesame ash, 30-50 parts of aged vinegar and 10-15 parts of auxiliary materials.

[0021] The auxiliary material of the present invention is one or two of white vaseline and honey.

[0022] The aging time of the aged vinegar of the present invention is 3 years or more.

[0023] The sesame ash of the present invention is preferably obtained by calcining sesame ash at 700-800°C for 1-2 hours, and more preferably by calcining sesame ash at 750°C for 1.5 hours and then crushing. The sesame ash obtained by the preparation method of the present invention has good antibacterial activity and astringent and anti-inflammatory effects.

[0024] The main drug of the Chinese medicinal ointment of the present invention is astragalus, which has the effects of invigorating qi and removing toxins, promoting skin repair, enhancing local immunity, inhibiting virus replication, shortening the course of herpes zoster, and can target the pathogenesis of herpes zoster of insufficient vital energy and internal toxic evil, and enhance the body's antiviral ability.

[0025] The auxiliary drugs of the Chinese medicine ointment of the present invention are amaranth and realgar. Amaranth can clear away heat and detoxify, cool blood and reduce swelling, directly inhibit the activity of herpes virus, and relieve skin redness, swelling, heat and pain; realgar has a detoxifying effect, and has an anti-inflammatory and analgesic effect on skin ulcers caused by herpes virus; the combination of the two can enhance the antiviral effect of the main drug astragalus, and quickly control the spread of herpes.

[0026] The adjuvants of the Chinese medicine ointment of the present invention are snake slough, needle sand and sesame ash. Snake slough can dispel wind and relieve itching, relieve neuralgia and promote epidermal regeneration; needle sand can astringe and dry dampness, reduce herpes exudate and prevent secondary infection; sesame ash can absorb toxins and assist in repairing damaged skin barriers.

[0027] The Chinese medicine ointment of the present invention comprises liquorice and aged vinegar. Licorice harmonizes various medicines, relieves pain and enhances the stability of drug efficacy; aged vinegar softens cuticle, activates blood circulation and removes blood stasis, promotes drug transdermal absorption and enhances local permeability.

[0028] The Chinese medicine ointment of the present invention comprises astragalus, amaranth and realgar which can inhibit virus replication, inhibit bacterial infection and reduce the risk of postherpetic neuralgia; the analgesic effect of realgar combined with the analgesic effect of licorice can quickly relieve acute pain; the astringent effect of snake slough, needle sand and sesame ash can reduce inflammatory exudation and promote scab healing; needle sand and aged vinegar can reduce the risk of pustule transformation. The combination of the medicines has the effects of antiviral, anti-inflammatory, analgesic and repairing, and has a significant effect on the treatment of herpes zoster.

[0029] The invention provides a preparation method of the above-mentioned traditional Chinese medicine ointment, comprising: extracting astragalus through pulse electric field to obtain astragalus extract; extracting amaranth and licorice through ethanol ultrasonic method to obtain amaranth-licorice extract; performing ultrasonic enzymolysis on snake exuviae through composite enzyme to obtain snake exuviae extract; and mixing the astragalus extract, amaranth-licorice extract, snake exuviae extract, needle sand, realgar, sesame ash, aged vinegar and auxiliary materials to obtain the traditional Chinese medicine ointment.

[0030] The solvent for the pulse electric field extraction of the present invention is preferably an ethanol solution with a volume percentage of 40%-50%, more preferably an ethanol solution with a volume percentage of 45%, the solid-liquid ratio is preferably 1:8-12g / mL, more preferably 1:10g / mL, the electric field strength is preferably 10-15kV / cm, more preferably 13kV / cm, the pulse width is preferably 30-40μs, more preferably 35μs, the number of pulses is preferably 5-10, more preferably 8, the temperature is preferably 30-40°C, more preferably 35°C, the time is preferably 5-10min, more preferably 8min. The pulse electric field extraction method can be used to extract the active ingredients used to treat herpes zoster in Astragalus efficiently at low temperature, thereby improving the efficacy.

[0031] In the ethanol ultrasonic extraction of the present invention, ethanol solution is used as the extraction solvent, the volume percentage of the ethanol solution is preferably 80%-90%, more preferably 85%, the solid-liquid ratio of the total amount of ultrasonically extracted Amaranthus and licorice to the solvent is preferably 1:5-10 g / mL, more preferably 1:8 g / mL, the extraction temperature is preferably 60-70°C, more preferably 65°C, the number of times is preferably 1-3 times, each time is preferably 30-40 min, more preferably 35 min.

[0032] The composite enzyme of ultrasonic enzymolysis of the present invention is preferably composed of keratinase and trypsin. The keratinase was purchased from Anhui Weimao Biotechnology Co., Ltd., with an enzyme activity of 100,000 U / g, and the item number is enzyme preparation 01; the trypsin was purchased from Xi'an Xinlu Biotechnology Co., Ltd., with an enzyme activity of 100,000 U / g, and the item number is XL-134; the mass ratio of the keratinase and trypsin is preferably 1:2-5, more preferably 1:3; the amount of the composite enzyme added is preferably 3-8% of the weight of the snake slough, more preferably 5%. The temperature of the ultrasonic enzymolysis is preferably 40-45°C, more preferably 42°C, the pH value is preferably 7.5-8.5, more preferably 8, the power is preferably 200-300W, more preferably 250W, the frequency is preferably 40-50kHz, more preferably 45kHz, and the time is preferably 30-40min, more preferably 35min. The present invention innovatively uses keratinase and trypsin as a composite enzyme to extract the effective ingredients in snake sloughs, which can increase and enrich the content of small molecule peptides and amino acids in snake sloughs that clear away heat and detoxify, reduce swelling and relieve pain, and enhance the drug activity of snake slough extracts in the treatment of herpes zoster.

[0033] The present invention also provides application of the above-mentioned traditional Chinese medicine ointment in preparing medicine for treating herpes zoster.

[0034] The method for using the Chinese medicinal ointment of the present invention is: after gently cleaning the affected area with warm water or a mild, non-irritating cleaning product, apply the Chinese medicinal ointment of the present invention on the affected area, 4 to 6 times a day, and a course of treatment of 7 to 10 days.

[0035] In the present invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0036] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] In the following embodiments, unless otherwise specified, all of them are conventional methods.

[0038] Unless otherwise specified, the materials, reagents, etc. used in the following examples and comparative examples can be obtained from commercial sources.

[0039] Keratinase was purchased from Anhui Weimao Biotechnology Co., Ltd. with an enzyme activity of 100,000 U / g and the catalog number enzyme preparation 01; trypsin was purchased from Xi'an Xinlu Biotechnology Co., Ltd. with an enzyme activity of 100,000 U / g and the catalog number XL-134; collagenase was purchased from Shanxi Tanrun Biotechnology Co., Ltd. with an enzyme activity of 100,000 U / g and the catalog number TR272; papain was purchased from Jiangsu Libin Bioengineering Co., Ltd. with an enzyme activity of 100,000 U / g and the catalog number 0215.

[0040] Example 1

[0041] Preparation of Chinese medicine ointment

[0042] (1) Selecting mature and dry sesame, drying at 60° C. to a moisture content of 2 wt %, calcining at 700° C. for 1.5 h, naturally cooling to 25° C., grinding through a 150-mesh sieve, and obtaining sesame ash;

[0043] (2) accurately weighing 20 parts of astragalus, 15 parts of amaranth, 10 parts of liquorice, 7 parts of snake skin, 2 parts of needle sand, 2 parts of realgar, 4 parts of sesame ash, 40 parts of aged vinegar (aged for 4 years), 8 parts of white vaseline and 5 parts of honey according to weight;

[0044] (3) crushing the astragalus root through a 400-mesh sieve, adding 45% (v / v) ethanol solution at a solid-liquid ratio of 1:10 g / mL, extracting by pulsed electric field at an electric field strength of 13 kV / cm, a pulse width of 35 μs, a pulse number of 8, and a temperature of 35° C. for 8 min, filtering, concentrating the filtrate under reduced pressure, and drying to obtain an astragalus root extract;

[0045] (4) Grinding Amaranthus and Licorice respectively, passing through a 200-mesh sieve, mixing, adding 85% (v / v) ethanol solution at a solid-liquid ratio of 1:8 g / mL, extracting at 65° C. for 35 min, filtering, adding 85% (v / v) ethanol solution to the residue at a solid-liquid ratio of 1:8 g / mL, extracting at 65° C. for 35 min, filtering, combining the filtrate, concentrating the filtrate under reduced pressure, and drying to obtain Amaranthus-Licorice extract;

[0046] (5) The snake skin was crushed and passed through a 300-mesh sieve, and distilled water was added according to a solid-liquid ratio of 1:20 g / mL. After soaking for 2 hours, a composite enzyme (composed of keratinase and trypsin in a mass ratio of 1:3) of 5% of the mass of the snake skin was added, and ultrasonic enzymolysis was performed at 42°C, pH 8, 250W, and 45kHz for 35 minutes, and the enzyme was inactivated at 85°C for 10 minutes. The filtrate was filtered, and the filtrate was concentrated and dried under reduced pressure to obtain a snake skin extract;

[0047] (6) Astragalus extract, Amaranthus-licorice extract, snake slough extract, needle sand, realgar, sesame ash and aged vinegar were mixed, stirred at 1000 r / min and 45°C for 20 min, white vaseline (pre-treated: heated to melt at 52°C) and honey were added, stirred at 200 r / min and 52°C for 15 min, and sterilized to obtain a Chinese medicine ointment.

[0048] Example 2

[0049] Preparation of Chinese medicine ointment

[0050] (1) Selecting mature and dry sesame, drying at 55° C. to a moisture content of 3 wt %, calcining at 600° C. for 2 h, naturally cooling to 25° C., grinding through a 120-mesh sieve, and obtaining sesame ash;

[0051] (2) accurately weighing 15 parts of astragalus, 10 parts of amaranth, 8 parts of liquorice, 5 parts of snake skin, 1 part of needle sand, 1 part of realgar, 3 parts of sesame ash, 30 parts of aged vinegar (aged for 3 years), 6 parts of white vaseline and 4 parts of honey according to weight;

[0052] (3) crushing the astragalus root through a 300-mesh sieve, adding 40% (v / v) ethanol solution at a solid-liquid ratio of 1:8 g / mL, extracting by pulsed electric field for 10 min at an electric field strength of 10 kV / cm, a pulse width of 30 μs, a pulse number of 5, and a temperature of 30° C., filtering, concentrating the filtrate under reduced pressure, and drying to obtain an astragalus root extract;

[0053] (4) Grinding Amaranthus and Licorice respectively through a 150-mesh sieve, mixing, adding 80% (v / v) ethanol solution at a solid-liquid ratio of 1:5 g / mL, extracting at 60° C. for 30 min, filtering, extracting the residue twice according to the above extraction method, combining the filtrate, concentrating the filtrate under reduced pressure, and drying to obtain Amaranthus-Licorice extract;

[0054] (5) The snake skin was crushed and passed through a 200-mesh sieve, distilled water was added according to a solid-liquid ratio of 1:15 g / mL, and after soaking for 2.5 hours, a complex enzyme (composed of keratinase and trypsin in a mass ratio of 1:2) of 3% of the mass of the snake skin was added, and ultrasonic enzymolysis was performed at 40°C, pH 7.5, 200W, and 40kHz for 40 minutes, and the enzyme was inactivated at 80°C for 15 minutes, filtered, and the filtrate was concentrated under reduced pressure and dried to obtain a snake skin extract;

[0055] (6) Astragalus extract, Amaranthus-licorice extract, snake slough extract, needle sand, realgar, sesame ash and aged vinegar were mixed, stirred at 900 r / min and 40°C for 30 min, white vaseline (pre-treated: heated to melt at 50°C) and honey were added, stirred at 150 r / min and 50°C for 20 min, and sterilized to obtain a Chinese medicine ointment.

[0056] Example 3

[0057] Preparation of Chinese medicine ointment

[0058] (1) Selecting mature and dry sesame, drying at 65° C. to a moisture content of 1 wt %, calcining at 800° C. for 1 h, naturally cooling to 25° C., grinding through a 200-mesh sieve, and obtaining sesame ash;

[0059] (2) accurately weighing 25 parts of astragalus, 20 parts of amaranth, 12 parts of liquorice, 8 parts of snake skin, 3 parts of needle sand, 3 parts of realgar, 5 parts of sesame ash, 50 parts of aged vinegar (aged for 5 years), 9 parts of white vaseline and 7 parts of honey according to weight;

[0060] (3) crushing the astragalus root through a 450-mesh sieve, adding 50% (v / v) ethanol solution at a solid-liquid ratio of 1:12 g / mL, extracting by pulsed electric field at an electric field strength of 15 kV / cm, a pulse width of 40 μs, a pulse number of 10, and a temperature of 40° C. for 5 min, filtering, concentrating the filtrate under reduced pressure, and drying to obtain an astragalus root extract;

[0061] (4) Grinding Amaranthus and Licorice respectively through a 250-mesh sieve, mixing, adding 90% (v / v) ethanol solution at a solid-liquid ratio of 1:10 g / mL, extracting at 70° C. for 40 min, filtering, concentrating the filtrate under reduced pressure, and drying to obtain Amaranthus-Licorice extract;

[0062] (5) The snake skin was crushed and passed through a 350 mesh sieve, distilled water was added according to a solid-liquid ratio of 1:25 g / mL, and after soaking for 2.5 hours, a composite enzyme (composed of keratinase and trypsin in a mass ratio of 1:5) of 8% of the mass of the snake skin was added, and ultrasonic enzymolysis was performed at 45°C, pH 8.5, 300W, and 50kHz for 30 minutes, and the enzyme was inactivated at 90°C for 8 minutes, filtered, and the filtrate was concentrated under reduced pressure and dried to obtain a snake skin extract;

[0063] (6) Astragalus extract, Amaranthus-licorice extract, snake slough extract, needle sand, realgar, sesame ash and aged vinegar were mixed, stirred at 1200 r / min and 48°C for 18 min, white vaseline (pre-treated: heated to melt at 55°C) and honey were added, stirred at 250 r / min and 55°C for 12 min, and sterilized to obtain a Chinese medicine ointment.

[0064] Comparative Example 1

[0065] The difference between this comparative example and Example 1 is that the ethanol solutions in step (3) and step (4) are replaced with distilled water.

[0066] Comparative Example 2

[0067] The difference between this comparative example and Example 1 is that step (5) is: crush the snake skin and pass it through a 300-mesh sieve, add distilled water at a solid-liquid ratio of 1:20 g / mL, soak for 2 hours, add 5% of the weight of the snake skin by complex enzyme (composed of collagenase and papain at a weight ratio of 1:3), ultrasonically hydrolyze for 35 minutes at 45°C, pH 7, 250W, and 45kHz, inactivate the enzyme at 85°C for 10 minutes, filter, and concentrate the filtrate under reduced pressure and dry to obtain a snake skin extract.

[0068] Comparative Example 3

[0069] The difference between this comparative example and Example 1 is that the aged vinegar is replaced by distilled water.

[0070] Comparative Example 4

[0071] The difference between this comparative example and Example 1 is that Astragalus is replaced by Scutellaria baicalensis.

[0072] Comparative Example 5

[0073] The difference between this comparative example and Example 1 is that: in step (5), the snake slough is crushed and passed through a 300-mesh sieve, distilled water is added according to a solid-liquid ratio of 1:20 g / mL, and after soaking for 2 hours, keratinase of 5% by weight of the snake slough is added, and ultrasonic enzymolysis is performed at 45°C, pH 7.5, 250W, and 45kHz for 35 minutes, the enzyme is inactivated at 85°C for 10 minutes, and the filtrate is filtered, and the filtrate is concentrated under reduced pressure and dried to obtain a snake slough extract.

[0074] Comparative Example 6

[0075] The difference between this comparative example and Example 1 is that: in step (5), the snake slough is crushed and passed through a 300-mesh sieve, distilled water is added according to a solid-liquid ratio of 1:20 g / mL, and after soaking for 2 hours, 5% trypsin by weight of the snake slough is added, and ultrasonic enzymolysis is performed at 37°C, pH 8, 250W, and 45kHz for 35 minutes, the enzyme is inactivated at 85°C for 10 minutes, and the filtrate is filtered, and the filtrate is concentrated under reduced pressure and dried to obtain a snake slough extract.

[0076] Animal experiments

[0077] An animal model of chronic infection with varicella-zoster virus was established with reference to the invention patent CN115040594A.

[0078] Preparation of varicella-zoster virus inoculum: MRC-5 cells were added to the culture medium DMEM / F12 to prepare a cell suspension. After counting the cells, 5 × 10 4 / cm 2 The concentration of 15×10 was inoculated into the culture flask, and then the MRC-5 cells were infected with varicella-zoster virus VZV. After 2 days of infection, the infected cells were collected and prepared into a virus inoculated cell suspension in PBS solution with a concentration of about 15×10 6pcs / 100μL.

[0079] A total of 130 SD rats weighing 300-320 g were randomly selected as the blank group. 50 μL of saline was injected into the left toe of the rats, and 50 μL of virus-inoculated cell suspension was injected into the left toe of other rats. Abnormal mechanical pain threshold after 3 days indicated successful modeling. 110 rats with successful modeling were selected and divided into a model group, a positive group (3% acyclovir cream), Example 1-3 group and Comparative Example 1-6 group, with 10 rats in each group. On the third day of modeling, 10 mg of the corresponding ointment was applied to the soles of the feet of the positive group, Example 1-3 group and Comparative Example 1-6 group, respectively, and the drug was administered continuously for 21 days.

[0080] (1) Testing of analgesic effects of traditional Chinese medicine ointments

[0081] The mechanical pain threshold can reflect the effect of drugs on neuralgia. An increase in the mechanical pain threshold indicates that the drug has a relieving effect on neuralgia.

[0082] The mechanical pain thresholds of rats in each group were tested before modeling and on the 7th and 21st days of drug administration. The specific results are shown in Table 1.

[0083] The method for detecting the mechanical pain threshold is as follows: a rat is placed alone in a transparent box until the rat's sniffer response disappears. The skin on the outer edge of the rat's right hind foot is subjected to the pressure generated by von Frey fiber filaments (0.2-30g pressure value), and the pressure gradually increases. When the rat shows a foot withdrawal reaction or licks its toes, the test is stopped and the intensity of the stimulus is recorded, which is the mechanical pain threshold.

[0084] Table 1 Mechanical pain threshold of rats in each group of Chinese medicine ointment (g)

[0085] Group Before modeling Day 7 of medication Day 21 of medication Blank Group 29.10±1.27 28.95±1.17 29.34±1.04 Model Group 27.36±1.37 10.30±0.29 6.97±0.32 Positive group 28.97±1.25 16.63±0.55 25.62±0.94 Example 1 27.41±1.13 15.24±0.43 23.93±0.78 Example 2 28.22±1.31 14.96±0.28 22.70±0.62 Example 3 27.23±0.94 14.52±0.32 22.55±0.50 Comparative Example 1 28.76±1.36 12.19±0.30 20.08±0.35 Comparative Example 2 27.58±1.29 13.07±0.41 21.47±0.46 Comparative Example 3 27.84±1.12 12.58±0.39 20.26±0.21 Comparative Example 4 29.67±1.14 11.84±0.24 19.31±0.43 Comparative Example 5 28.67±1.38 11.73±0.22 18.36±0.38 Comparative Example 6 27.53±1.06 11.46±0.25 18.07±0.35

[0086] As can be seen from the data in Table 1, the mechanical pain thresholds of rats in each group before modeling are not much different, indicating that there is no significant difference between the groups. Compared with the positive group, Examples 1-3 can also significantly improve the mechanical pain threshold of rats. As can be seen from the comparison between Example 1 and Comparative Example 1, different solvents extract different components in Chinese medicine, resulting in different drug effects; as can be seen from the comparison between Example 1 and Comparative Example 2 and Comparative Example 5-6, different enzymes are used to enzymolyze snake sloughs, which may generate different polypeptides and amino acids, thereby affecting the drug effect. There is a synergistic effect between keratinase and trypsin, and the two enzymolyze snake sloughs, which can improve the efficacy of Chinese medicine ointment in relieving itching, relieving neuralgia, and promoting epidermal regeneration; as can be seen from the comparison between Example 1 and Comparative Example 3, aged vinegar has the effects of promoting blood circulation and removing blood stasis, promoting penetration, and can improve drug effect relative to distilled water; as can be seen from the comparison between Example 1 and Comparative Example 4, changing the monarch medicine has a significant effect on the therapeutic effect. The results of Table 1 show that the Chinese medicine ointment of the present invention can significantly relieve the central pain caused by varicella-zoster virus.

[0087] (2) Therapeutic effects of Chinese medicine ointments

[0088] After infection with varicella-zoster virus, a series of immune responses will be induced in the body and the levels of multiple cytokines will change significantly. Inflammatory factors can reflect the therapeutic effect of drugs on herpes zoster. The therapeutic effect of traditional Chinese medicine ointment was examined by measuring the levels of IL-6 and TNF-α in rat blood.

[0089] 24 hours after the last administration, the rats in each group were decapitated and blood was collected. The blood was centrifuged at 3000 r / min for 15 min, and the IL-6 and TNF-α levels in the plasma were determined using ELISA kits. The specific results are shown in Table 2.

[0090] Table 2 IL-6 and TNF-α levels in rats in each group

[0091]

[0092]

[0093]

[0094] As shown in Table 2, the positive group, the embodiment group and the comparative example group significantly reduced the IL-6 and TNF-α contents relative to the model group, indicating that each group of ointments can inhibit the release of proinflammatory factors to varying degrees, and alleviate the central hyperalgesia and peripheral nervous system damage caused by varicella-zoster virus. As shown in the data comparison of Example 1 and Comparative Examples 1-6, the Chinese medicine ointment prepared by the method of the present invention can better inhibit the expression of IL-6 and TNF-α. As shown in the data comparison of Example 1 and Comparative Examples 5-6, there is a synergistic effect between keratinase and trypsin, which can improve the Chinese medicine ointment to inhibit the release of proinflammatory factors, alleviate central hyperalgesia and peripheral nervous system damage. The difference in IL-6 and TNF-α contents in the blood of the positive group and the embodiment 1-3 group of rats is not large, indicating that the Chinese medicine ointment obtained by the preparation method of the present invention has a significant effect in treating herpes zoster.

[0095] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicinal ointment for external application to treat herpes zoster, characterized in that: The invention comprises the following raw materials in parts by weight: 15-25 parts of astragalus, 10-20 parts of amaranth, 8-12 parts of liquorice, 5-8 parts of snake skin, 1-3 parts of needle sand, 1-3 parts of realgar, 3-5 parts of sesame ash, 30-50 parts of aged vinegar and 10-15 parts of auxiliary materials.

2. The Chinese medicine ointment according to claim 1, characterized in that The auxiliary materials are one or two of white vaseline and honey.

3. The Chinese medicine ointment according to claim 1, characterized in that, The aging time of the aged vinegar is 3 years or more.

4. The Chinese medicine ointment according to claim 1, characterized in that, The flax ash is obtained by calcining flax ash at 700-800° C. for 1-2 hours.

5. The method for preparing the Chinese medicine ointment according to any one of claims 1 to 4, characterized in that: include: Astragalus is extracted by pulse electric field to obtain Astragalus extract; Amaranthus and licorice were extracted by ethanol ultrasonic to obtain Amaranthus-licorice extract; The snake exuviae are hydrolyzed by ultrasonic compound enzymes to obtain the snake exuviae extract; The astragalus extract, the amaranth-licorice extract, the snake exuvia extract, needle sand, realgar, sesame ash, aged vinegar and auxiliary materials are mixed to obtain the traditional Chinese medicine ointment.

6. The preparation method according to claim 5, characterized in that: The solvent for the pulse electric field extraction is an ethanol solution with a volume percentage of 40%-50%, the solid-liquid ratio of the extracted astragalus to the solvent is 1:8-12g / mL, the electric field strength is 10-15kV / cm, the pulse width is 30-40μs, the number of pulses is 5-10, the temperature is 30-40℃, and the time is 5-10min.

7. The preparation method according to claim 5, characterized in that: In the ethanol ultrasonic extraction, ethanol solution is used as the extraction solvent, the volume percentage of the ethanol solution is 80%-90%, the solid-liquid ratio of the total amount of ultrasonically extracted Amaranthus and licorice to the solvent is 1:5-10g / mL, the extraction temperature is 60-70°C, the number of times is 1-3, and each time is 30-40min.

8. The preparation method according to claim 5, characterized in that: The complex enzyme consists of keratinase and trypsin.

9. The preparation method according to claim 5, characterized in that: The temperature of the ultrasonic enzymolysis is 40-45° C., the pH value is 7.5-8.5, the power is 200-300 W, the frequency is 40-50 kHz, and the time is 30-40 min.

10. Use of the Chinese medicinal ointment according to any one of claims 1 to 4 or the Chinese medicinal ointment obtained by the preparation method according to any one of claims 5 to 9 in preparing a drug for treating herpes zoster.

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