Application of traditional Chinese medicine composition in preparation of medicine for herpes zoster

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating herpes zoster, which is characterized in that the traditional Chinese medicine composition is prepared from prepared monkshood, dried ginger, honey-fried licorice root, honeysuckle, spina gleditsiae, humulus scandens, pogostemon cablin and pericarpium citri reticulatae. The composition provided by the invention can promote the absorption of herpes zoster, shorten the scabbing and healing time of herpes zoster, and significantly reduce the heat pain threshold, and has a good treatment effect on herpes zoster.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, relates to a new use of a traditional Chinese medicine composition, and specifically relates to an application of the traditional Chinese medicine composition in preparing a medicine for herpes zoster. Background Art

[0002] Herpes zoster is a viral infection caused by the reactivation of the varicella-zoster virus (the virus that causes chickenpox), which manifests as a painful rash. The varicella-zoster virus is a member of the herpes virus family (herpesvirus type 3). The virus is neurotropic and can remain dormant in the dorsal root ganglia of the spinal cord or the sensory ganglia of the cranial nerves for a long time. When the body is stimulated by some kind of stimulus (such as trauma, fatigue, malignant tumors or weakness after illness, etc.), which causes the body's resistance to decrease, the latent virus is activated and travels down along the sensory nerve axons to the skin in the area innervated by the nerve to replicate and produce blisters. At the same time, the affected nerves become inflamed and necrotic, causing neuralgia, which affects the patient's quality of life. Herpes zoster has two main symptoms: one is the rash, which is distributed along the nerves and often only appears on one side of the body, and the herpes is distributed in clusters; the other is pain, which varies in manifestation and degree, including dull pain, radiating pain, knife-like pain, lightning pain, tearing pain, etc. Generally speaking, patients can be cured in about a week of medication, but about 9%-34% of patients will experience postherpetic neuralgia, and the incidence of neuralgia will gradually increase with age. In view of the above problems, the field of traditional Chinese medicine should actively intervene in the prevention and treatment of herpes zoster and develop prescriptions for the symptoms. Summary of the invention

[0003] In order to solve the above technical problems, the present invention provides a use of a Chinese medicine composition in the preparation of a drug for herpes zoster, wherein the Chinese medicine composition is prepared from cooked aconite root, dried ginger, roasted licorice root, honeysuckle, Gleditsia sinensis, Ipomoea australis, patchouli and dried tangerine peel. The use may be any method that is beneficial to improving the corresponding symptoms of the patient, including treatment or prevention.

[0004] Specifically, the use for herpes zoster includes significantly shortening the time for herpes scab formation and healing, and lowering the heat pain threshold.

[0005] The present invention also provides an application of a traditional Chinese medicine composition in preparing a drug for treating neuralgia, wherein the neuralgia is preferably postherpetic neuralgia.

[0006] Further, the Chinese medicine composition comprises: 1-50 parts of cooked aconite, 1-50 parts of dried ginger, 1-50 parts of roasted licorice, 1-50 parts of honeysuckle, 1-50 parts of Gleditsia sinensis, 1-50 parts of Ipomoea australis, 1-50 parts of patchouli, and 1-50 parts of dried tangerine peel. The composition of the present invention can be directly ground into powder, or it can be an extract prepared by conventional means in the art. The Chinese medicine used in the composition of the present invention can also be used in the form of direct grinding into powder, extracts, or other processed forms.

[0007] Furthermore, the Chinese medicine composition includes: 10-20 parts of cooked aconite, 10-15 parts of dried ginger, 20-25 parts of roasted licorice, 10-15 parts of honeysuckle, 10-20 parts of Gleditsia sinensis, 20-30 parts of Ipomoea australis, 10-12 parts of patchouli, and 5-10 parts of tangerine peel.

[0008] Furthermore, the Chinese medicine composition includes: 10-12 parts of cooked aconite, 12-15 parts of dried ginger, 20-22 parts of roasted licorice, 10-12 parts of honeysuckle, 10-12 parts of Gleditsia sinensis, 20-22 parts of Ipomoea australis, 10-12 parts of patchouli, and 5-6 parts of tangerine peel.

[0009] Preferably, the Chinese medicine composition comprises: 10 parts of cooked aconite root, 15 parts of dried ginger, 20 parts of roasted licorice root, 10 parts of honeysuckle, 10 parts of Gleditsia sinensis, 20 parts of Ipomoea australis, 10 parts of patchouli, and 5 parts of tangerine peel.

[0010] In some embodiments, the aforementioned medicine further comprises a medically acceptable carrier and / or excipient. Specifically, the carrier or excipient may be a carrier or excipient commonly used in the art, including fillers, disintegrants, lubricants, suspending agents, adhesives, sweeteners, flavoring agents, preservatives, and substrates, specifically including but not limited to starch, lactose, glucose, sodium carboxymethyl cellulose, ethyl cellulose and methyl cellulose, malt, gelatin, polyols (such as propylene glycol, glycerol, mannitol), compressed tablets, etc., to help improve the stability of the pharmaceutical composition or increase the activity, or produce an acceptable taste or smell in the case of oral administration.

[0011] In some embodiments, the composition can be prepared into granules, tablets, capsules, pills, oral solutions, oral suspensions or oral emulsions using existing traditional Chinese medicine preparation methods, thereby facilitating clinical administration.

[0012] Furthermore, the preparation method of the traditional Chinese medicine composition includes taking cooked aconite, dried ginger, roasted licorice, honeysuckle, Gleditsia sinensis, Ipomoea australis, patchouli, and tangerine peel, adding 8 to 12 times the total mass of water of the raw materials, heating to boiling, keeping slightly boiling for 1 to 2 hours, and obtaining a first decoction and medicinal residues after separation; for the second time, taking the medicinal residues obtained after the first decoction, adding 6 to 10 times the total mass of water of the raw materials, heating to boiling, keeping slightly boiling for 1 to 2 hours, and obtaining a second decoction and medicinal residues after separation; combining the first decoction and the second decoction to prepare a decoction, and decompressing and concentrating the decoction filtrate to obtain a clear paste, and crushing it.

[0013] When the composition of the present invention is used as a drug for treating herpes zoster, an oral solution can be used. Severe patients are given one dose per day, divided into 2 to 3 oral or nasogastric administrations, once every 6 to 8 hours; critical patients are given two doses per day, divided into two oral or nasogastric administrations in the morning and evening, once every 8 to 12 hours; mild patients are given one dose per day, orally or nasogastric administration. Each dose is 150 to 250 ml.

[0014] When the medicine is in the form of granules or tablets, the dosage is converted into a decoction dose and then taken orally.

[0015] Clinical trials have shown that the pharmaceutical composition of the present invention can significantly reduce the deterioration of patients, especially for severe and critical patients. Moreover, it also has a certain therapeutic effect on severe and critical patients.

[0016] The composition of the present invention can promote the absorption of herpes zoster, shorten the time of herpes scab formation and healing, and significantly reduce the heat pain threshold, indicating that the Chinese medicine composition has a certain therapeutic and analgesic effect on herpes zoster and neuralgia. DETAILED DESCRIPTION

[0017] As mentioned above, the present invention aims to provide a use of a Chinese medicine composition in the preparation of a drug for treating herpes zoster. The following will be described in detail in conjunction with the contents of a specific experiment.

[0018] The following experiments, if no specific conditions are specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The APIs or excipients, reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be purchased commercially. Unless otherwise specified, all percentages, ratios, proportions or parts are by weight.

[0019] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention.

[0020] Example 1 Preparation of Chinese medicine composition

[0021] Take 10 kg of cooked aconite, 15 kg of dried ginger, 20 kg of roasted licorice, 10 kg of honeysuckle, 10 kg of Gleditsia sinensis, 20 kg of Ipomoea australis, 10 kg of Patchouli, and 5 kg of dried tangerine peel, add 8 times the total mass of water of the raw materials, heat to boiling, keep slightly boiling for 1 hour, and separate to obtain the first decoction and residue; for the second time, take the residue obtained after the first decoction, add 8 times the total mass of water of the raw materials, heat to boiling, keep slightly boiling for 1 hour, and separate to obtain the second decoction and residue; combine the first decoction and the second decoction to obtain a decoction, reduce the pressure on the decoction filtrate and concentrate it to obtain a clear paste, grind it into fine powder to obtain a Chinese medicine composition, add an appropriate amount of maltodextrin, mix well, and granulate to obtain Chinese medicine composition granules.

[0022] Experimental Example 2 Effect of Chinese herbal medicine combination on VZV-induced herpes zoster in rabbits

[0023] 1. Experimental Materials

[0024] 1.1 Animals

[0025] New Zealand rabbits, ordinary grade, 12 pieces, weighing 1.8-2.2kg, half male and half female, provided by Life Breeding Farm in Pukou District, Nanjing.

[0026] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, single cage breeding.

[0027] 1.2 Drugs, etc.

[0028] The Chinese medicine composition prepared in Example 1 was provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; acyclovir tablets were provided by Guangdong BIDI Pharmaceutical Co., Ltd., batch number 20230103; varicella-zoster virus (VZV) was provided by the ABSL-2+ laboratory of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.

[0029] 1.3 Instruments

[0030] Electronic balance (Sartorius Scientific Instruments, model BS224S); Electronic balance (G&G, model TC3K).

[0031] 2. Dosage design

[0032] The daily dosage of the Chinese medicine composition is 100 g of crude drug / day. According to the body surface area conversion method, the equivalent dose for rabbits is 100 g / 60 kg*3.1=5.17 g of crude drug / kg.

[0033] The daily dosage of acyclovir tablets is 4g / day. According to the body surface area conversion method, the equivalent dose for rabbits is 4g / 60kg*3.1=0.21g / kg.

[0034] 3. Experimental Methods

[0035] The rabbits were adaptively fed for 5 days, with free access to feed and water, and randomly divided into a model group, an acyclovir group, and a Chinese medicine combination group according to body weight, with 4 rabbits in each group, half male and half female.

[0036] The rabbits were observed for 2 days after depilation and confirmed to be healthy. After that, 1 mL of VZV virus (concentration 1×10 6 PFU / mL) to prepare the herpes zoster rabbit model. The model group was given double distilled water, and the acyclovir and Chinese medicine composition groups were given corresponding doses of drugs, 10mL / kg intragastric administration, once a day, for 7 consecutive days. The herpes condition, scab time and recovery time were observed with the naked eye every day. The scab time is the time from the start of treatment to the herpes completely drying up and scab; the recovery time is the time from the start of treatment to the disappearance of all experimental symptoms.

[0037] 4. Statistical methods

[0038] The results were statistically analyzed using t-test.

[0039] 5. Experimental Results

[0040] After the rabbits were inoculated with VZV virus, herpes gradually developed within 1 to 2 days. The herpes swelled and became round. The wall of the herpes was bright and clear and then gradually became turbid. The blister groups gradually appeared and showed a trend of expansion. The skin between the herpes groups was normal. In addition, the rabbits showed decreased appetite, slowed breathing, and increased body temperature.

[0041] After administration of double distilled water, acyclovir and Chinese medicine combination, the crusting time and healing time of acyclovir and Chinese medicine combination groups were statistically different from those of the model group (P<0.05). See Table 1.

[0042] Table 1 Effects of VZV on herpes zoster in rabbits

[0043]

[0044] Note: Compared with the model group, *P<0.05.

[0045] 6. Experimental conclusion

[0046] The Chinese medicine composition can promote the absorption of herpes zoster and shorten the time of herpes scab formation and healing, indicating that the Chinese medicine composition has a certain therapeutic effect on herpes zoster.

[0047] Experimental Example 3 Effect of Chinese herbal medicine combination on VZV-induced neuralgia in mice

[0048] 1. Experimental Materials

[0049] 1.1 Animals

[0050] C57BL / 6J mice, SPF grade, weighing 18-22 g, female, were provided by the Comparative Medicine Center of Yangzhou University.

[0051] Rearing environment: room temperature 20-26℃, relative humidity controlled at 40-70%. Raise in separate cages, 5 per cage.

[0052] 1.2 Drugs

[0053] The Chinese medicine composition was prepared according to the method of Example 1 and provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; acyclovir tablets, Guangdong Buddy Pharmaceutical Co., Ltd., batch number 20230103; chloral hydrate, Sinopharm Chemical Reagent Co., Ltd., batch number 20200320; varicella-zoster virus (VZV), provided by ABSL-2+ Laboratory, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.

[0054] 1.3 Instruments

[0055] Electronic balance (Sartorius Scientific Instruments, model BS224S); animal weighing scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model ACX-SC-DA); intelligent hot plate instrument (Tianjin Zongke Technology Co., Ltd., model YLS-6B).

[0056] 2. Dosage design

[0057] The daily dosage of the Chinese medicine composition is 100 g of crude drug / day. According to the body surface area conversion method, the equivalent dose for mice is 100 g / 60 kg*12.3=20.5 g of crude drug / kg.

[0058] The daily dosage of acyclovir tablets is 4 g / day. According to the body surface area conversion method, the equivalent dose for mice is 4 g / 60 kg*12.3=0.82 g / kg.

[0059] 3. Experimental Methods

[0060] The normal pain threshold of C57BL / 6J female mice was measured on a hot plate at (55±0.5)℃. The positive index is the time when the mouse starts to lick its hind paw. Less than 5s indicates an allergic reaction, and more than 30s indicates a too slow reaction. Mice with allergic or too slow reactions are not used. Female mice with a pain threshold of 5 to 30s were taken. After using 10% chloral hydrate, the left lower limb and back were depilated with a depilatory agent and the depilated area was rinsed with clean water. After 3 days, animals with smooth and undamaged depilatory areas were selected to enter the following experiments. Animals with skin injuries were eliminated and supplemented with an equal number of animals. They were randomly divided into 3 groups, namely the model group, the acyclovir group, and the Chinese medicine combination group, with 10 mice in each group. In the experimental group, 10ul of VZV (concentration of 1×10 6PFU / mL). Each drug group was given oral administration from the day of inoculation, the model group was given double distilled water, and the acyclovir and Chinese medicine combination groups were given corresponding doses of drugs, 20mL / kg oral administration, once a day for 7 consecutive days. The heat pain threshold was measured on the 7th day after inoculation.

[0061] 4. Statistical methods

[0062] The results were statistically analyzed using t-test.

[0063] 5. Experimental Results

[0064] After mice were inoculated with VZV virus, the heat pain threshold increased significantly, which is consistent with the literature that postherpetic neuralgia (PHN) often manifests as highly sensitive tenderness, but the heat pain threshold is abnormally absent. Compared with the model group, acyclovir and the Chinese medicine combination can significantly reduce the heat pain threshold, with statistically significant differences (P<0.001). See Table 2.

[0065] Table 2 Effects on VZV-induced neuropathic pain in mice

[0066]

[0067] Note: Compared with the model group, ***P<0.001.

[0068] 6. Experimental conclusion

[0069] The Chinese herbal composition can reduce the thermal pain threshold, indicating that the Chinese herbal composition has a certain analgesic effect on neuralgia.

[0070] The above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for herpes zoster, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 1-50 parts of cooked aconite root, 1-50 parts of dried ginger, 1-50 parts of roasted licorice root, 1-50 parts of honeysuckle, 1-50 parts of Gleditsia sinensis thorns, 1-50 parts of Ipomoea australis, 1-50 parts of patchouli, and 1-50 parts of tangerine peel.

2. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following components by weight: 10-20 parts of cooked aconite root, 10-15 parts of dried ginger, 20-25 parts of roasted licorice root, 10-15 parts of honeysuckle, 10-20 parts of Gleditsia sinensis thorns, 20-30 parts of Ipomoea australis, 10-12 parts of patchouli, and 5-10 parts of tangerine peel.

3. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following components by weight: 10-12 parts of cooked aconite root, 12-15 parts of dried ginger, 20-22 parts of roasted licorice root, 10-12 parts of honeysuckle, 10-12 parts of Gleditsia sinensis thorns, 20-22 parts of Ipomoea australis, 10-12 parts of patchouli, and 5-6 parts of tangerine peel.

4. The use according to claim 1, characterized in that: The traditional Chinese medicine composition consists of the following components: 10 parts of cooked aconite root, 15 parts of dried ginger, 20 parts of roasted licorice root, 10 parts of honeysuckle, 10 parts of Gleditsia sinensis thorns, 20 parts of Ipomoea australis, 10 parts of patchouli, and 5 parts of tangerine peel.

5. The use according to any one of claims 1 to 4, characterized in that: The medicament for treating herpes zoster includes pharmaceutically acceptable excipients or additives.

6. The use according to claim 5, characterized in that The pharmaceutically acceptable adjuvants or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

7. The use according to claim 6, characterized in that: The dosage form of the herpes zoster drug includes an oral dosage form, an injection dosage form or an external dosage form.

8. The use according to claim 4, characterized in that: The medicine is in the form of granules, tablets, capsules, pills, oral solutions, oral suspensions or oral emulsions.

9. The use according to claims 1-4, characterized in that: The preparation method of the traditional Chinese medicine composition comprises the following steps: taking cooked aconite root, dried ginger, roasted licorice root, honeysuckle, thorn of Gleditsia sinensis, five-clawed dragon, patchouli, and tangerine peel, adding 8 to 12 times of water equivalent to the total mass of the raw materials, heating to boiling, maintaining a slight boiling for 1 to 2 hours, and obtaining a first decoction and medicinal residues after separation; a second time, taking the medicinal residues obtained after the first decoction, adding 6 to 10 times of water equivalent to the total mass of the raw materials, heating to boiling, maintaining a slight boiling for 1 to 2 hours, and obtaining a second decoction and medicinal residues after separation; combining the first decoction and the second decoction to prepare a decoction, and reducing the pressure to concentrate the decoction filtrate to obtain a clear paste, and crushing it.

10. Use of a Chinese medicine composition in preparing a drug for treating neuralgia, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 1-50 parts of cooked aconite root, 1-50 parts of dried ginger, 1-50 parts of roasted licorice root, 1-50 parts of honeysuckle, 1-50 parts of Gleditsia sinensis thorns, 1-50 parts of Ipomoea australis, 1-50 parts of patchouli, and 1-50 parts of tangerine peel.

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