Traditional Chinese medicine ointment for treating herpes zoster as well as preparation method and application thereof

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine ointment for treating herpes zoster and a preparation method and application thereof. The traditional Chinese medicine ointment is prepared from the following raw materials in parts by weight: 10-20 parts of raw sanguisorba officinalis, 10-20 parts of spina gleditsiae, 10-20 parts of raw liquorice and 5-15 parts of rhizoma smilacis glabrae. According to the traditional Chinese medicine ointment, the raw sanguisorba officinalis, the spina gleditsiae, the raw liquorice and the rhizoma smilacis glabrae are reasonably combined for use according to the theory of syndrome differentiation and treatment of traditional Chinese medicine, and the ointment has the effects of diminishing inflammation, relieving pain, promoting blood circulation, detoxifying, expelling pus and promoting tissue regeneration.

Description

Technical Field

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

[0002] Herpes zoster (HZ) is a neurocutaneous viral disease that may occur at any age. HZ is sporadic, with a lifetime prevalence of 25-50% worldwide. HZ is an acute viral skin disease caused by infection with the varicella-zoster virus (VZV). People with low immunity often present with chickenpox or latent infection after the first infection with VZV. The virus then moves to the sensory nerve endings of the skin and lurks in the dorsal root ganglia of the spinal cord. Under the stimulation of various triggers, the virus is reactivated to invade the ganglia, causing inflammation and necrosis. Therefore, the skin lesions and pain of patients with herpes zoster are often distributed along one side of the peripheral nerves. The primary infection of VZV mainly occurs in childhood. HZ can cause a variety of complications, including postherpetic neuralgia (PHN), conjunctivitis, encephalitis, ear function damage, visceral function damage, etc. The pain associated with persistent herpes zoster is the most common complication of the disease.

[0003] There is no record of postherpetic neuralgia in ancient Chinese medicine. Herpes zoster is equivalent to "snake sores" in Chinese medicine. The cause of the disease is related to external evil, diet, and emotions. Improper treatment of herpes zoster can lead to pain after the skin lesions disappear. Modern doctors call it postherpetic neuralgia (PHN), and believe that the key to the occurrence of this disease is the blockage of the meridians. The remaining evil stays, blood stasis is stored, and the blockage causes pain; the internal organs are out of harmony, the meridians are not nourished, and the lack of nourishment causes pain. According to the severity of the disease and the deficiency and excess of the symptoms and the root cause, a variety of treatment ideas such as treatment based on poison, treatment based on stasis, treatment based on deficiency, and treatment based on internal organs have been proposed. Combined with traditional Chinese medicine external treatments such as fire needles, acupuncture, and buried needles, the analgesic effect is obvious and the adverse reactions are few. It has become a popular choice for the treatment of PHN. Topical medications are indispensable for the treatment of herpes zoster. Good topical medications can prevent, treat and alleviate the symptoms of postherpetic neuralgia. The invention adopts the treatment mode of external ointment to obtain an effective traditional Chinese medicine ointment and is applied to the clinical treatment of herpes zoster, which can enhance the clinical efficacy and alleviate the pain of patients. Summary of the invention

[0004] In view of the above-mentioned deficiencies, the present invention provides a traditional Chinese medicine ointment for treating herpes zoster based on the theory of traditional Chinese medicine, and a preparation method and application thereof, which has the effects of anti-inflammatory and analgesic, promoting blood circulation and detoxification, and draining pus and promoting tissue regeneration, and can be safely applied to all stages of herpes zoster.

[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0006] A traditional Chinese medicine ointment for treating herpes zoster is prepared from the following raw materials in parts by weight: 10-20 parts of raw sanguisorba officinalis, 10-20 parts of gleditsia sinensis, 10-20 parts of raw liquorice, and 5-15 parts of smilax glabra.

[0007] Preferably, the Chinese medicine ointment is made of the following raw materials in parts by weight: 20 parts of raw Sanguisorba officinalis, 10 parts of Gleditsia sinensis, 10 parts of raw licorice, and 10 parts of Smilax glabra.

[0008] Preferably, the Chinese medicine ointment is made of the following raw materials in parts by weight: 10 parts of raw Sanguisorba officinalis, 20 parts of Gleditsia sinensis, 20 parts of raw licorice, and 10 parts of Smilax glabra.

[0009] Furthermore, the present invention also provides a method for preparing a traditional Chinese medicine ointment for treating herpes zoster, comprising the following steps:

[0010] (1) Weigh raw Sanguisorba officinalis, Gleditsia sinensis, raw Licorice root, and Smilax glabra according to the prescribed amount, add water and boil for 3 times, add 8-12 times the amount of water for the first time, boil for 1-3 hours, and filter; add 6-10 times the amount of water for the second time, boil for 0.5-2 hours, and filter; add 4-8 times the amount of water for the third time, boil for 20-40 minutes, and filter; combine the three filtrates, concentrate under reduced pressure to an extract with a relative density of 1.50 g / mL at 60° C., and set aside;

[0011] (2) placing the oil phase component in a beaker, heating in a water bath until melted, and continuing to heat to 70°C-80°C to obtain an oil phase solution;

[0012] (3) Place glycerin, emulsifier, preservative, and purified water in another beaker, heat in a water bath until completely dissolved, then add the extract, stir evenly, and continue heating to 70°C-80°C to obtain an aqueous solution;

[0013] (4) At the same temperature, slowly add the aqueous solution to the oil phase solution while stirring, stop stirring when the solution is cooled to 40-50° C., and naturally cool to room temperature to obtain the Chinese medicine ointment.

[0014] Preferably, step (1) comprises: weighing raw Sanguisorba officinalis, Gleditsia sinensis, raw licorice and Smilax glabra according to the prescribed amount, adding water and decocting for 3 times, adding 10 times the amount of water for the first time, decocting for 2 hours, and filtering; adding 8 times the amount of water for the second time, decocting for 1 hour, and filtering; adding 6 times the amount of water for the third time, decocting for 30 minutes, and filtering; combining the three filtrates, concentrating under reduced pressure to an extract with a relative density of 1.50 g / mL at 60° C., and setting aside.

[0015] Preferably, the oil phase component in step (2) includes one or more of stearic acid, white vaseline, and glyceryl monostearate.

[0016] Preferably, the emulsifier in step (3) includes one or more of triethanolamine and sodium lauryl sulfate.

[0017] Preferably, the preservative in step (3) is selected from ethylparaben or phenoxyethanol.

[0018] Preferably, the stirring speed in step (4) is 200-400 rpm.

[0019] Furthermore, the present invention also provides the use of the traditional Chinese medicine ointment in preparing a medicine for treating herpes zoster.

[0020] Raw Sanguisorba officinalis: The root of Sanguisorba officinalis and Sanguisorba officinalis of the Rosaceae family. It is bitter, sour, cold, and non-toxic. Sanguisorba officinalis is cold in nature and has the effect of clearing away heat and detoxifying. It is mainly used to treat sores, carbuncle, swelling and pain, eczema, vulva itching, burns caused by water or fire, and snake and insect bites.

[0021] Gleditsia thorn: Gleditsia thorn is the thorn of Gleditsia sinensis and Gleditsia sinensis, which belong to the genus Gleditsia of the Leguminosae family. It has the functions of removing wind, removing toxins, reducing swelling and draining pus. It can treat carbuncles, sores, leprosy and ringworm.

[0022] Raw licorice: It has the effects of harmonizing the stomach and relieving urgency, moistening the lungs, detoxifying, and harmonizing various medicines. It is used raw to treat sore throat, carbuncle swelling, fetal toxicity in children, and drug and food poisoning.

[0023] Smilax glabra: clears away heat and detoxifies, removes dampness, and promotes joint function. Modern pharmacological studies have shown that it can be used for limb cramps and muscle and bone pain caused by syphilis and mercury poisoning; damp-heat stranguria, leucorrhea, carbuncle, scrofula, and scabies.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The Chinese medicine ointment of the present invention is based on the theory of TCM syndrome differentiation and treatment, and uses raw Sanguisorba officinalis, Gleditsia sinensis, raw liquorice and Rhizoma Smilacis Glabrae in reasonable combination, with the effects of anti-inflammatory and analgesic, blood circulation and detoxification, pus discharge and granulation. Compared with the multi-flavor complex prescription in the prior art, the prescription of the present invention is streamlined, the curative effect is clear, and each component cooperates with each other, and the symptoms caused by herpes zoster can be significantly alleviated. In addition, the present invention adopts water-in-oil type matrix, by screening the oil phase component and the emulsifier type, it is beneficial to the release of the active ingredient in the ointment and the penetration of the stratum corneum, and it is easy to operate, and the sense of use is refreshing and not greasy, and there is good spreadability, and the patient is easy to accept. The Chinese medicine ointment of the present invention has the advantages of low cost, safety and reliability, and remarkable effect, and provides a new means for alleviating the symptoms of herpes zoster patients. DETAILED DESCRIPTION

[0026] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only some embodiments of the present invention, rather than all embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work are within the scope of protection of the present invention. The materials, reagents, etc. used, unless otherwise specified, are reagents and materials available from commercial sources.

[0027] Example 1 Chinese medicine ointment for treating herpes zoster

[0028] Prescription quantity: by weight, 20 parts of raw Sanguisorba officinalis, 10 parts of Gleditsia sinensis, 10 parts of raw licorice, and 10 parts of Smilax glabra.

[0029] Preparation method:

[0030] (1) Weigh raw Sanguisorba officinalis, Gleditsia sinensis, raw licorice, and Smilax glabra according to the prescribed amount, add water and boil for 3 times. For the first time, add 10 times the amount of water, boil for 2 hours, and filter; for the second time, add 8 times the amount of water, boil for 1 hour, and filter; for the third time, add 6 times the amount of water, boil for 30 minutes, and filter; combine the three filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.50 g / mL at 60°C, and set aside;

[0031] (2) Place 10 g of stearic acid, 5 g of white vaseline, and 5 g of glyceryl monostearate in a beaker, heat in a water bath until melted, and continue heating to 75° C. to obtain an oil phase solution;

[0032] (3) Place 15 g of glycerol, 10 g of triethanolamine, 0.5 g of phenoxyethanol, and 80 g of purified water in another beaker, heat in a water bath until completely dissolved, then add 10 g of the extract, stir evenly, and continue heating to 75° C. to obtain an aqueous phase solution;

[0033] (4) At the same temperature, slowly add the aqueous solution to the oil phase solution while stirring at a stirring speed of 300 rpm. Stop stirring when the solution is cooled to 45° C. and cool naturally to room temperature to obtain the Chinese medicine ointment.

[0034] Example 2 Chinese medicine ointment for treating herpes zoster

[0035] Prescription quantity: by weight, 10 parts of raw Sanguisorba officinalis, 20 parts of Gleditsia sinensis, 20 parts of raw licorice, and 10 parts of Smilax glabra.

[0036] Preparation method:

[0037] (1) Weigh raw Sanguisorba officinalis, Gleditsia sinensis, raw licorice, and Smilax glabra according to the prescribed amount, add water and boil for 3 times. For the first time, add 10 times the amount of water, boil for 2 hours, and filter; for the second time, add 8 times the amount of water, boil for 1 hour, and filter; for the third time, add 6 times the amount of water, boil for 30 minutes, and filter; combine the three filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.50 g / mL at 60°C, and set aside;

[0038] (2) Place 10 g of stearic acid, 5 g of white vaseline, and 5 g of glyceryl monostearate in a beaker, heat in a water bath until melted, and continue heating to 75° C. to obtain an oil phase solution;

[0039] (3) Place 15 g of glycerol, 10 g of sodium lauryl sulfate, 0.5 g of ethylparaben, and 80 g of purified water in another beaker, heat in a water bath until completely dissolved, then add 10 g of the extract, stir evenly, and continue heating to 75° C. to obtain an aqueous solution;

[0040] (4) At the same temperature, slowly add the aqueous solution to the oil phase solution while stirring at a stirring speed of 300 rpm. Stop stirring when the solution is cooled to 45° C. and cool naturally to room temperature to obtain the Chinese medicine ointment.

[0041] Comparative Example 1 (Compared with Example 1, the prescription amount is different)

[0042] Prescription quantity: by weight, 5 parts of raw Sanguisorba officinalis, 25 parts of Gleditsia sinensis, 5 parts of raw licorice, and 20 parts of Smilax glabra.

[0043] The preparation method is the same as that of Example 1.

[0044] Comparative Example 2 (Compared with Example 1, the prescription amount is different)

[0045] Prescription quantity: by weight, 25 parts of raw Sanguisorba officinalis, 5 parts of Gleditsia sinensis, 5 parts of raw licorice, and 20 parts of Smilax glabra.

[0046] The preparation method is the same as that of Example 1.

[0047] Comparative Example 3 (Compared with Example 1, using pangolin instead of Gleditsia sinensis)

[0048] Prescription quantity: by weight, 20 parts of raw Sanguisorba officinalis, 10 parts of pangolin, 10 parts of raw licorice, and 10 parts of wild yam.

[0049] The preparation method is the same as that of Example 1.

[0050] Comparative Example 4 (Compared with Example 1, using Sophora japonica flower instead of Sanguisorba officinalis)

[0051] Prescription quantity: by weight, 20 parts of Sophora japonica flowers, 10 parts of Gleditsia sinensis, 10 parts of raw licorice, and 10 parts of Smilax glabra.

[0052] The preparation method is the same as that of Example 1.

[0053] Comparative Example 5 (Compared with Example 1, using different types of oil phase components and emulsifiers)

[0054] Preparation method: Compared with Example 1, octadecyl alcohol and isononyl isononanoate are used to replace stearic acid and white vaseline respectively, and glyceryl monostearate is used to replace triethanolamine.

[0055] Comparative Example 6 (Chinese medicine formula for external use for treating herpes zoster in prior art CN105412722A)

[0056] A Chinese medicine formula for external use to treat herpes zoster is prepared from the following raw materials in parts by weight: 15 grams of borneol, 10 grams of realgar, 20 grams of smilax glabra, 30 grams of acutus agkistrodon, and 20 grams of sanguisorba officinalis. Preparation method: Dry the borneol, realgar, smilax glabra, acutus agkistrodon, and sanguisorba officinalis in the sun, and grind them together into foam.

[0057] Pharmacological efficacy experimental study

[0058] Experimental animals

[0059] Healthy SPF-grade Kunming female mice weighing (20±2) g were selected and purchased from Liaoning Changsheng Biotechnology Co., Ltd. Before the experiment, they were adaptively fed for 1 week and had free access to water and food.

[0060] Dosage

[0061] One day before the experiment, the mouse abdomen was depilated, and the depilation range was about 3cm 2 The commonly recommended dose for a 60kg subject is 0.3g / 5cm 2 According to the equivalent dose conversion of body surface area, the dosage for a 20g mouse is 0.04g / cm 2 Therefore, the dosage for mice in this experiment was 0.04 g / cm 2 ×3cm 2 =0.12g.

[0062] Experimental methods

[0063] In an experimental environment with a constant temperature of 22°C, the temperature of the hot plate was precisely controlled to 55°C ± 0.5°C. Mice were selected as experimental animal models and placed on the hot plate one by one. The time (in seconds) taken by the mice to lick their hind feet was defined as the reaction time. The average of the reaction time obtained from two measurements was taken as the basic pain threshold before administration. In this process, individual mice whose licking time was shorter than 5 seconds or longer than 30 seconds were eliminated. After screening, 80 qualified mice were obtained and randomly divided into 10 groups, 8 in each group. The specific groups included a blank control group, a Voltaren positive control group (the latex dose was 0.12 g / mouse, produced by Beijing Novartis Pharmaceuticals Co., Ltd.), Example 1-2 group, and Comparative Example 1-6 group. According to the established grouping scheme, the corresponding dose of the tested ointment was evenly applied to the surface of the mouse abdominal skin, covered with a breathable film and medical gauze, and fixed with medical tape to ensure that the drug was in full contact with the skin. The drug action lasted for no less than 4 hours after each administration, and the drug was administered once a day for 3 consecutive days. At 30 minutes, 60 minutes, and 90 minutes after the last administration, the mice were placed on the hot plate again, and the time required for the mice to lick their hind feet was recorded as the pain threshold after administration.

[0064] At the same time, the acetic acid writhing experiment was carried out. Following the same experimental preparatory process as above, 80 qualified mice were selected and randomly divided into 10 groups of 8 mice in each group. The grouping was consistent with the hot plate method experiment. According to the grouping results, the corresponding dose of ointment was carefully and evenly applied to the abdomen of the mouse, covered with a breathable film and medical gauze and fixed with medical tape to ensure that the drug was in contact with the skin for at least 4 hours after each administration. The drug was administered once a day for 3 consecutive days. One hour after the last administration, each mouse was intraperitoneally injected with 0.6% glacial acetic acid solution at a dose of 0.1 mL / 10 g. The frequency of writhing caused by pain stimulation in the mouse was then closely observed and recorded within 15 minutes.

[0065] Experimental Results

[0066] 1. Comparison of pain thresholds of mice in each group (see Table 1)

[0067] Table 1 Comparison of pain threshold of mice before and after treatment

[0068]

[0069]

[0070] 2. Comparison of the number of writhing times of mice in each group (see Table 2)

[0071] Table 2 Number of writhing of mice in each group

[0072]

[0073] It can be seen from the hot plate method experimental results in Table 1 that after administration, both Example 1-2 group and Voltaren group had analgesic effects in three time periods. Among them, at 30 minutes and 60 minutes, the analgesic effects of Example 1-2 group and Voltaren group were similar, but after 90 minutes, the pain threshold of mice in Example 1-2 group was significantly higher than that in Voltaren group, which shows that the Chinese medicine ointment in Example 1-2 group has a better long-term anti-inflammatory and analgesic effect. Similarly, it can be seen from the acetic acid twisting method experimental results in Table 2 that Example 1-2 group has a better anti-inflammatory and analgesic effect than Voltaren group.

[0074] From the experimental results of Example 1 and Comparative Examples 1-5, when the ratio of Gleditsia sinensis, Radix Sanguisorbae, Radix Glycyrrhizae, and Radix Smilacis Glabrae is 2:1:1:1 or 1:2:2:1, the anti-inflammatory and analgesic effect is the best. When similar medicinal flavors such as Flos Sophorae and Scabra are used to replace Radix Sanguisorbae and Gleditsia sinensis, the anti-inflammatory and analgesic effect is significantly reduced. Regarding the selection of ointment auxiliary ingredients, considering that the water phase in the oil-in-water matrix accounts for a large proportion, it is easy to spoil and breed bacteria, so preservatives-hydroxyethyl ethyl ester or phenoxyethanol are added; in order to prevent the evaporation of water in the ointment and maintain the moist microenvironment of the wound surface, moisturizing agent glycerol is added; oil phase and emulsion form can reduce the volatilization of drug moisture, and the selection of appropriate types of oil phase components and emulsifiers can help the drug adhere and strengthen the hydration of the drug and the stratum corneum of the skin, which is beneficial to the release of active pharmaceutical ingredients in the ointment and the penetration of the stratum corneum. It can be seen that the present invention screens and optimizes the prescription of Chinese medicine ointment from the aspects of prescription ratio, replacement of similar medicinal flavors, selection of oil phase components and emulsifier types, so that the prescription and compatibility of Chinese medicine ointment are more reasonable, the curative effect is more clear, and the components cooperate with each other, which can significantly alleviate the symptoms caused by herpes zoster. From the experimental results of Example 1 and Comparative Example 6, compared with the multi-flavor complex prescriptions in the prior art, the prescription of the present invention is more streamlined, the curative effect of anti-inflammatory and analgesic is clearer, and while reducing costs and simplifying the preparation process, significant therapeutic effects are also achieved.

[0075] In summary, the Chinese medicine ointment of the present invention adopts a specific combination of raw materials and dosage ratio, has reasonable compatibility, low cost, wide drug source, high bioavailability, and has a good effect on the treatment of postherpetic neuralgia.

[0076] The above description is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several modifications or equivalent substitutions can be made to the technical solution without departing from the principle of the present invention. These modifications or equivalent substitutions should also be regarded as the protection scope of the present invention.

Claims

1. A Chinese medicinal ointment for treating herpes zoster, characterized in that: The traditional Chinese medicine ointment is prepared from the following raw materials in parts by weight: 10-20 parts of raw Sanguisorba officinalis, 10-20 parts of Gleditsia sinensis, 10-20 parts of raw liquorice, and 5-15 parts of Smilax glabra.

2. The Chinese medicine ointment according to claim 1, characterized in that, The Chinese medicine ointment is prepared from the following raw materials in parts by weight: 20 parts of raw Sanguisorba officinalis, 10 parts of Gleditsia sinensis, 10 parts of raw liquorice, and 10 parts of Smilax glabra.

3. The Chinese medicine ointment according to claim 1, characterized in that, The Chinese medicine ointment is prepared from the following raw materials in parts by weight: 10 parts of raw Sanguisorba officinalis, 20 parts of Gleditsia sinensis, 20 parts of raw liquorice, and 10 parts of Smilax glabra.

4. A method for preparing a Chinese medicinal ointment for treating herpes zoster according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) Weigh raw Sanguisorba officinalis, Gleditsia sinensis, raw Licorice root, and Smilax glabra according to the prescribed amount, add water and boil for 3 times, add 8-12 times the amount of water for the first time, boil for 1-3 hours, and filter; add 6-10 times the amount of water for the second time, boil for 0.5-2 hours, and filter; add 4-8 times the amount of water for the third time, boil for 20-40 minutes, and filter; combine the three filtrates, concentrate under reduced pressure to an extract with a relative density of 1.50 g / mL at 60° C., and set aside; (2) placing the oil phase component in a beaker, heating in a water bath until melted, and continuing to heat to 70°C-80°C to obtain an oil phase solution; (3) Place glycerin, emulsifier, preservative, and purified water in another beaker, heat in a water bath until completely dissolved, then add the extract, stir evenly, and continue heating to 70°C-80°C to obtain an aqueous solution; (4) At the same temperature, slowly add the aqueous phase solution to the oil phase solution while stirring, stop stirring when the solution is cooled to 40-50° C., and naturally cool to room temperature to obtain the Chinese medicine ointment.

5. The preparation method according to claim 4, characterized in that: Step (1) is: weigh raw sanguisorba officinalis, gleditsia sinensis, raw licorice and rhizoma smilax according to the prescribed amount, add water and boil for 3 times, add 10 times the amount of water for the first time, boil for 2 hours, and filter; add 8 times the amount of water for the second time, boil for 1 hour, and filter; add 6 times the amount of water for the third time, boil for 30 minutes, and filter; combine the three filtrates, and concentrate under reduced pressure to an extract with a relative density of 1.50 g / mL at 60° C. for later use.

6. The preparation method according to claim 4, characterized in that: The oil phase component in step (2) includes one or more of stearic acid, white vaseline, and glyceryl monostearate.

7. The preparation method according to claim 4, characterized in that: The emulsifier in step (3) includes one or more of triethanolamine and sodium lauryl sulfate.

8. The preparation method according to claim 4, characterized in that: The preservative in step (3) is selected from ethylparaben or phenoxyethanol.

9. The preparation method according to claim 4, characterized in that: The stirring speed in step (4) is 200-400 rpm.

10. Use of the traditional Chinese medicine ointment according to any one of claims 1 to 3 in preparing a medicine for treating herpes zoster.

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