A pain relief preparation, its preparation method and application

Abstract

The present invention belongs to the technical field of pain relief preparations, and particularly relates to a pain relief preparation, a preparation method thereof and an application. The pain relief preparation is composed of (+)-camphene, a propylene glycol extract of Bupleurum chinense DC. and pharmaceutically acceptable excipients. Among them, the mass ratio of (+)-camphene to the propylene glycol extract of Bupleurum chinense DC. is 1-2.5:1. The propylene glycol extract of Bupleurum chinense DC. is prepared by the following method: Bupleurum chinense DC. is ground into powder, mixed with propylene glycol, extracted by ultrasonic treatment, filtered, the filtrate is collected and dried to obtain the propylene glycol extract of Bupleurum chinense DC. The present invention also provides a preparation method of the pain relief preparation, and proves the application of the pain relief preparation in relieving acute pain and postherpetic neuralgia, expanding the types of pain relief preparations.

Description

Technical Field

[0001] The present invention belongs to the technical field of pain relief preparations, and particularly relates to a pain relief preparation, a preparation method thereof, and an application thereof. Background Art

[0002] Many diseases are accompanied by pain symptoms, such as bacterial infections, viral infections, etc. Pain will affect the normal life of patients. Therefore, it is necessary to relieve pain.

[0003] In the prior art, the means for relieving pain mainly include: taking preparations such as ibuprofen and paracetamol, performing local anesthesia with lidocaine patches, etc., pulsed radiofrequency treatment, and short-term spinal cord electrical stimulation. Among them, the means of relieving pain with preparations are more convenient and more widely used. For example, the preparations that can be currently used to relieve pain symptoms include: (1) antiviral preparations, such as acyclovir tablets, valacyclovir tablets, etc., which can help kill viruses in the body and relieve pain symptoms; (2) non-steroidal anti-inflammatory preparations: such as ibuprofen tablets, indomethacin tablets, diclofenac sodium sustained-release capsules, etc., which can help relieve fever and pain; (3) central nervous system preparations: such as gabapentin capsules, pregabalin capsules, etc., which can mildly inhibit the central nervous system and relieve discomfort symptoms such as itching; (4) tricyclic antidepressant preparations: such as amitriptyline hydrochloride tablets, imipramine hydrochloride tablets, etc., patients with postherpetic neuralgia may experience symptoms such as anxiety and depression due to long-term pain, resulting in the perception of increased pain. At this time, the above preparations can be used for treatment; (5) traditional Chinese medicine preparations for promoting blood circulation and regulating qi, such as Chaihu Shugan Powder, Taohong Siwu Decoction, Xuefu Zhuyu Decoction, etc., which can help promote blood circulation to remove blood stasis and then relieve pain symptoms. However, due to the differences in the constitutions of different patients, their sensitivities and drug resistances to the existing analgesic preparations are different, so it is necessary to continue to develop pain relief preparations. Summary of the Invention

[0004] In order to solve the above technical problems, the present invention provides a pain relief preparation, a preparation method thereof, and an application thereof. The pain relief preparation can relieve acute pain and can also relieve postherpetic neuralgia.

[0005] The object of the present invention is to provide a pain relief preparation, which is composed of (+)-camphene, the propylene glycol extract of Bupleurum chinense, and pharmaceutically acceptable excipients. Among them, the mass ratio of (+)-camphene to the propylene glycol extract of Bupleurum chinense is 1-2.5:1. The propylene glycol extract of Bupleurum chinense is prepared according to the following method: Bupleurum chinense is ground into powder, mixed with propylene glycol, ultrasonically extracted, filtered, the filtrate is collected, and dried to obtain the propylene glycol extract of Bupleurum chinense.

[0006] According to the research results of the present invention, after (+)-camphene is combined with the propylene glycol extract of Bupleurum chinense, and then formulated with pharmaceutically acceptable excipients to form a mixture preparation, (+)-camphene and the propylene glycol extract of Bupleurum chinense have a synergistic analgesic effect in relieving acute pain or postherpetic neuralgia. In addition, in the pain relief preparation of the present invention, (+)-camphene is mainly used to relieve pain related to nerve injury, and it can regulate the body's immune function and inhibit pain signal conduction; the propylene glycol extract of Bupleurum chinense contains saikosaponins, volatile oils and sterols, which can promote blood circulation and reduce the conduction of pain signals; therefore, after (+)-camphene is combined with the propylene glycol extract of Bupleurum chinense, the effect of reducing pain signal conduction is enhanced, acute pain can be relieved, and it also has an obvious relieving effect on postherpetic neuralgia.

[0007] In addition, according to the research results of the present invention, when (+)-camphene acts alone, its analgesic effect in relieving acute pain or postherpetic neuralgia is weak; when the propylene glycol extract of Bupleurum chinense acts alone, its analgesic effect in relieving acute pain or postherpetic neuralgia is also weak.

[0008] In addition, after Bupleurum chinense is ground into powder, the particle size becomes smaller and the surface area increases, making the contact with the solvent propylene glycol more sufficient. With the assistance of ultrasonic extraction, saikosaponins, volatile oils and sterols can be dissolved in propylene glycol. After filtration, collection of the filtrate and drying operations, a propylene glycol extract of Bupleurum chinense rich in saikosaponins, volatile oils and sterols can be obtained.

[0009] Preferably, in the pain relief preparation, the mass ratio of (+)-camphene to the propylene glycol extract of Bupleurum chinense is 2:1, and the pain relief effect is relatively good.

[0010] Preferably, in the pain relief preparation, the conditions for ultrasonic extraction are ultrasonic extraction for 30 minutes at a power of 400W. Under these ultrasonic conditions, the solubility of saikosaponins, volatile oils and sterols in propylene glycol is high.

[0011] Preferably, the specific preparation method of the propylene glycol extract of Bupleurum chinense is as follows: Bupleurum chinense is ground into powder with a mesh size of 40, mixed with propylene glycol in a ratio of 1 kg: 8 L, ultrasonic extracted for 30 minutes at a power of 400W, filtered through a 50-mesh sieve, and the collected filtrate is dried to obtain the propylene glycol extract of Bupleurum chinense.

[0012] Preferably, in the pain relief preparation, the pharmaceutically acceptable excipients include at least any one of the following situations:

[0013] (a) The pharmaceutically acceptable excipients are a combination of propylene glycol and water;

[0014] (b) The pharmaceutically acceptable excipient is propylene glycol;

[0015] (c) A combination of pharmaceutically acceptable excipients, hydroxypropyl-β-cyclodextrin, propylene glycol, and water.

[0016] It should be noted that the "combination" in the pharmaceutically acceptable excipients refers to raw materials that use multiple pharmaceutically acceptable excipients. These raw materials can be mixed and then used, or used separately.

[0017] Preferably, in the pain relief preparation, the concentration of (+)-borneol in the pain relief preparation is 60 ng / mL to 80 ng / mL.

[0018] Preferably, in the pain relief preparation, the concentration of (+)-borneol in the pain relief preparation is 75 ng / mL.

[0019] The present invention provides a method for preparing a pain relief preparation, which comprises mixing (+)-borneol, the propylene glycol extract of Bupleurum chinense DC., and pharmaceutically acceptable excipients, and the obtained mixture is the pain relief preparation.

[0020] Preferably, when the pharmaceutically acceptable excipient is a combination of propylene glycol and water; the method for preparing the pain relief preparation includes: dissolving (+)-borneol in propylene glycol to obtain a (+)-borneol liquid; dissolving the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense DC.; mixing the (+)-borneol liquid with the propylene glycol extract liquid of Bupleurum chinense DC. to obtain a pain relief preparation, which is suitable for intramuscular injection.

[0021] Preferably, when the pharmaceutically acceptable excipient is propylene glycol; the method for preparing the pain relief preparation includes: dissolving (+)-borneol in propylene glycol to obtain a (+)-borneol liquid; dissolving the propylene glycol extract of Bupleurum chinense DC. in propylene glycol to obtain a propylene glycol extract liquid of Bupleurum chinense DC.; mixing the (+)-borneol liquid with the propylene glycol extract liquid of Bupleurum chinense DC. to obtain a pain relief preparation, which is suitable for nasal drops.

[0022] Preferably, when the pharmaceutically acceptable excipient is a combination of excipient hydroxypropyl-β-cyclodextrin, propylene glycol, and water; the method for preparing the pain relief preparation includes: encapsulating (+)-borneol in hydroxypropyl-β-cyclodextrin to obtain a (+)-borneol liquid; dissolving the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense DC.; mixing the (+)-borneol liquid with the propylene glycol extract liquid of Bupleurum chinense DC. to obtain a pain relief preparation, which is suitable for intramuscular injection.

[0023] The present invention provides an application of a pain relief preparation, and the application refers to relieving acute pain or relieving postherpetic neuralgia.

[0024] Preferably, in the application of the pain relief preparation, the postherpetic neuralgia is pain caused by varicella-zoster virus.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The pain relief preparation of the present invention is composed of borneol, the propylene glycol extract of Bupleurum chinense, and pharmaceutically acceptable excipients; wherein, the mass ratio of borneol to the propylene glycol extract of Bupleurum chinense is 1-2.5:1; the preparation method of the propylene glycol extract of Bupleurum chinense is as follows: grind Bupleurum chinense into powder, mix it with propylene glycol, extract by ultrasonic wave, filter, collect the filtrate, and dry it to obtain the propylene glycol extract of Bupleurum chinense. After the combination of borneol and the propylene glycol extract of Bupleurum chinense, together with pharmaceutically acceptable excipients, a mixture preparation is formed. In the pain relief preparation of the present invention for relieving acute pain or postherpetic neuralgia, borneol and the propylene glycol extract of Bupleurum chinense have a synergistic analgesic effect. Detailed implementation manners

[0027] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention will be further described below with reference to specific embodiments.

[0028] In the description of the present invention, unless otherwise specified, the reagents used are commercially available, and the methods used are conventional techniques in the art.

[0029] In the following examples and experimental processes, borneol was purchased from Jiangxi Linkelong Borneol Technology Co., Ltd., which is made from the fresh branches and leaves of Cinnamomum camphora of the Lauraceae family. The content of borneol is ≥96%, and the packaging specification is 500 g / bag. According to medical research results, borneol has analgesic, anti-inflammatory, and sleep-improving effects.

[0030] Bupleurum chinense was purchased from a traditional Chinese medicine store. According to medical research results, Bupleurum chinense has the effects of antipyretic and anti-inflammatory, soothing the liver and relieving depression, lifting yang qi, and reconciling the shaoyang.

[0031] In the pain relief preparation of the present invention, the substances that play a role in relieving pain are borneol and the propylene glycol extract of Bupleurum chinense. After the two are combined with pharmaceutically acceptable excipients, they can be made into intramuscular injections or nasal drops, both of which have the effect of relieving pain, and the relieving pain refers to acute pain or relieving postherpetic neuralgia.

[0032] When the pharmaceutically acceptable excipients are a combination of propylene glycol and water; the preparation method of the pain relief preparation includes: dissolving borneol in propylene glycol to obtain a borneol liquid; dissolving the propylene glycol extract of Bupleurum chinense in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense; mixing the borneol liquid with the propylene glycol extract liquid of Bupleurum chinense to obtain a pain relief preparation, which is suitable for intramuscular injection. Among them, the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1.

[0033] When the pharmaceutically acceptable excipient is propylene glycol, the preparation method of the pain relief preparation includes: dissolving borneol in propylene glycol to obtain a borneol liquid; dissolving the propylene glycol extract of Bupleurum chinense in propylene glycol to obtain a propylene glycol extract liquid of Bupleurum chinense; mixing the borneol liquid with the propylene glycol extract liquid of Bupleurum chinense to obtain a pain relief preparation suitable for nasal drops.

[0034] When the pharmaceutically acceptable excipient is a combination of excipient hydroxypropyl-β-cyclodextrin, propylene glycol and water, the preparation method of the pain relief preparation includes: encapsulating borneol in hydroxypropyl-β-cyclodextrin to obtain a borneol liquid; dissolving the propylene glycol extract of Bupleurum chinense in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense; mixing the borneol liquid with the propylene glycol extract liquid of Bupleurum chinense to obtain a pain relief preparation suitable for intramuscular injection. Among them, the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1.

[0035] The following takes the dosage form of intramuscular injection and related animal experiments to illustrate the examples of the present invention and the corresponding pain relief effect.

[0036] Example 1

[0037] A pain relief preparation is composed of borneol, the propylene glycol extract of Bupleurum chinense and a pharmaceutically acceptable excipient; among them, the mass ratio of borneol to the propylene glycol extract of Bupleurum chinense is 1:1.

[0038] The preparation method of the propylene glycol extract of Bupleurum chinense is as follows: grind Bupleurum chinense into a powder of 40 meshes, mix it with propylene glycol according to the ratio of 1 kg: 8 L, carry out ultrasonic extraction for 30 min at a power of 400 W, filter with a 50-mesh sieve, and the collected filtrate is freeze-dried at -20 °C to obtain the propylene glycol extract of Bupleurum chinense.

[0039] The pharmaceutically acceptable excipient is a combination of propylene glycol and water.

[0040] The preparation method of the pain relief preparation is as follows: dissolve borneol in propylene glycol to obtain a borneol liquid; dissolve the propylene glycol extract of Bupleurum chinense in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; based on the mass ratio of borneol to the propylene glycol extract of Bupleurum chinense being 1:1, prepare the borneol liquid and the propylene glycol extract liquid of Bupleurum chinense, and then mix the borneol liquid with the propylene glycol extract liquid of Bupleurum chinense to obtain a pain relief preparation, and the concentration of borneol in the pain relief preparation is 75 ng / mL.

[0041] Example 2

[0042] A pain relief preparation, which consists of (+)-camphol, the propylene glycol extract of Bupleurum chinense DC., and pharmaceutically acceptable excipients; wherein, the mass ratio of (+)-camphol to the propylene glycol extract of Bupleurum chinense DC. is 1.5:1.

[0043] The preparation method of the propylene glycol extract of Bupleurum chinense DC. is as follows: Grind Bupleurum chinense DC. into powder with a mesh size of 40, mix it with propylene glycol according to the ratio of 1 kg: 8 L, perform ultrasonic extraction for 30 min at a power of 400 W, filter through a 50-mesh sieve, and freeze-dry the collected filtrate at -20 °C to obtain the propylene glycol extract of Bupleurum chinense DC.

[0044] The pharmaceutically acceptable excipients are a combination of propylene glycol and water.

[0045] The preparation method of the pain relief preparation is as follows: Dissolve (+)-camphol in propylene glycol to obtain a (+)-camphol liquid; dissolve the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense DC.; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; Prepare the (+)-camphol liquid and the propylene glycol extract liquid of Bupleurum chinense DC. according to the mass ratio of (+)-camphol to the propylene glycol extract of Bupleurum chinense DC. being 1.5:1, and then mix the (+)-camphol liquid and the propylene glycol extract liquid of Bupleurum chinense DC. to obtain the pain relief preparation, and the concentration of (+)-camphol in the pain relief preparation is 75 ng / mL.

[0046] Example 3

[0047] A pain relief preparation, which consists of (+)-camphol, the propylene glycol extract of Bupleurum chinense DC., and pharmaceutically acceptable excipients; wherein, the mass ratio of (+)-camphol to the propylene glycol extract of Bupleurum chinense DC. is 2:1.

[0048] The preparation method of the propylene glycol extract of Bupleurum chinense DC. is as follows: Grind Bupleurum chinense DC. into powder with a mesh size of 40, mix it with propylene glycol according to the ratio of 1 kg: 8 L, perform ultrasonic extraction for 30 min at a power of 400 W, filter through a 50-mesh sieve, and freeze-dry the collected filtrate at -20 °C to obtain the propylene glycol extract of Bupleurum chinense DC.

[0049] The pharmaceutically acceptable excipients are a combination of propylene glycol and water.

[0050] The preparation method of the pain relief preparation is as follows: Dissolve (+)-camphol in propylene glycol to obtain a (+)-camphol liquid; dissolve the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense DC.; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; Prepare the (+)-camphol liquid and the propylene glycol extract liquid of Bupleurum chinense DC. according to the mass ratio of (+)-camphol to the propylene glycol extract of Bupleurum chinense DC. being 2:1, and then mix the (+)-camphol liquid and the propylene glycol extract liquid of Bupleurum chinense DC. to obtain the pain relief preparation, and the concentration of (+)-camphol in the pain relief preparation is 75 ng / mL.

[0051] Example 4

[0052] A pain relief preparation, which is composed of (+)-campherenol, the propylene glycol extract of Bupleurum chinense DC., and pharmaceutically acceptable excipients; wherein, the mass ratio of (+)-campherenol to the propylene glycol extract of Bupleurum chinense DC. is 2.5:1.

[0053] The preparation method of the propylene glycol extract of Bupleurum chinense DC. is as follows: Grind Bupleurum chinense DC. into a powder of 40 meshes, mix it with propylene glycol according to the ratio of 1 kg: 8 L, perform ultrasonic extraction for 30 min at a power of 400 W, filter through a 50-mesh sieve, and lyophilize the collected filtrate at -20 °C to obtain the propylene glycol extract of Bupleurum chinense DC.

[0054] The pharmaceutically acceptable excipients are a combination of propylene glycol and water.

[0055] The preparation method of the pain relief preparation is as follows: Dissolve (+)-campherenol in propylene glycol to obtain a (+)-campherenol liquid; dissolve the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a liquid of the propylene glycol extract of Bupleurum chinense DC.; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; calculate based on the mass ratio of (+)-campherenol to the propylene glycol extract of Bupleurum chinense DC. being 2.5:1, prepare the (+)-campherenol liquid and the liquid of the propylene glycol extract of Bupleurum chinense DC., and then mix the (+)-campherenol liquid and the liquid of the propylene glycol extract of Bupleurum chinense DC. to obtain the pain relief preparation, and the concentration of (+)-campherenol in the pain relief preparation is 75 ng / mL.

[0056] Example 5

[0057] A pain relief preparation, which is composed of (+)-campherenol, the propylene glycol extract of Bupleurum chinense DC., and pharmaceutically acceptable excipients; wherein, the mass ratio of (+)-campherenol to the propylene glycol extract of Bupleurum chinense DC. is 2:1.

[0058] The preparation method of the propylene glycol extract of Bupleurum chinense DC. is as follows: Grind Bupleurum chinense DC. into a powder of 40 meshes, mix it with propylene glycol according to the ratio of 1 kg: 8 L, perform ultrasonic extraction for 30 min at a power of 400 W, filter through a 50-mesh sieve, and lyophilize the collected filtrate at -20 °C to obtain the propylene glycol extract of Bupleurum chinense DC.

[0059] The pharmaceutically acceptable excipients are a combination of propylene glycol and water.

[0060] The preparation method of the pain relief preparation is as follows: Dissolve (+)-campherenol in propylene glycol to obtain a (+)-campherenol liquid; dissolve the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a liquid of the propylene glycol extract of Bupleurum chinense DC.; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; calculate based on the mass ratio of (+)-campherenol to the propylene glycol extract of Bupleurum chinense DC. being 2:1, prepare the (+)-campherenol liquid and the liquid of the propylene glycol extract of Bupleurum chinense DC., and then mix the (+)-campherenol liquid and the liquid of the propylene glycol extract of Bupleurum chinense DC. to obtain the pain relief preparation, and the concentration of (+)-campherenol in the pain relief preparation is 60 ng / mL.

[0061] Example 6

[0062] A pain relief preparation is composed of (+)-campheol, the propylene glycol extract of Bupleurum chinense DC., and pharmaceutically acceptable excipients; wherein, the mass ratio of (+)-campheol to the propylene glycol extract of Bupleurum chinense DC. is 2:1.

[0063] The preparation method of the propylene glycol extract of Bupleurum chinense DC. is as follows: Grind Bupleurum chinense DC. into powder with a mesh size of 40, mix it with propylene glycol according to the ratio of 1 kg: 8 L, perform ultrasonic extraction for 30 min at a power of 400 W, filter through a 50-mesh sieve, and freeze-dry the collected filtrate at -20 °C to obtain the propylene glycol extract of Bupleurum chinense DC.

[0064] The pharmaceutically acceptable excipients are a combination of propylene glycol and water.

[0065] The preparation method of the pain relief preparation is as follows: Dissolve (+)-campheol in propylene glycol to obtain a (+)-campheol liquid; dissolve the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense DC.; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; based on the mass ratio of (+)-campheol to the propylene glycol extract of Bupleurum chinense DC. being 2:1, prepare the (+)-campheol liquid and the propylene glycol extract liquid of Bupleurum chinense DC., and then mix the (+)-campheol liquid and the propylene glycol extract liquid of Bupleurum chinense DC. to obtain the pain relief preparation, and the concentration of (+)-campheol in the pain relief preparation is 80 ng / mL.

[0066] The differences between Examples 1 to 4 lie in the different mass ratios of (+)-campheol to the propylene glycol extract of Bupleurum chinense DC. In Example 1, the mass ratio of (+)-campheol to the propylene glycol extract of Bupleurum chinense DC. is 1:1; in Example 2, the mass ratio of (+)-campheol to the propylene glycol extract of Bupleurum chinense DC. is 1.5:1; in Example 3, the mass ratio of (+)-campheol to the propylene glycol extract of Bupleurum chinense DC. is 2:1; in Example 4, the mass ratio of (+)-campheol to the propylene glycol extract of Bupleurum chinense DC. is 2.5:1. The differences between Examples 3, 5 and 6 lie in that the concentrations of (+)-campheol in the pain relief preparation are 75 ng / mL, 60 ng / mL, and 80 ng / mL respectively.

[0067] The dosage forms of Examples 1 to 6 are all intramuscular injection agents, and the usage methods are all intramuscular injection.

[0068] Next, explore the analgesic effects of the pain relief preparations of Examples 1 to 6.

[0069] Experiment 1. Intramuscular injection experiment of virus model

[0070] (1) Main experimental materials and animals

[0071] CV-1 cells: Purchased from Shanghai Yaji Biotechnology Co., Ltd., and the brand is Yaji Biology.

[0072] Complete medium: DMEM / F12.

[0073] Female mice: body weight 30±0.2g.

[0074] (2) Grouping and modeling

[0075] Take CV-1 cells in complete culture medium to make a cell suspension, inoculate it in a culture dish, and the inoculation concentration is 5×10 5 Pieces / cm 2 , and then infected with varicella-zoster virus. When more than 80% of CV-1 cells were infected with varicella-zoster virus, the infected cells were collected, washed in 0.1 mol / L, pH 7.2 phosphate buffer, and resuspended to obtain a concentration of 10×10 7 The varicella-zoster virus is specifically VZV-rOka, which is provided by Xiamen University.

[0076] 132 female mice were randomly divided into 11 groups, with 12 mice in each group; the names of the 11 groups were blank group, model group, borneol group, propylene glycol extract of Bupleurum group, Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, Example 6 group and drug control group.

[0077] The treatment of female mice in the blank group was as follows: 50 μL of normal saline was injected subcutaneously into the left toe.

[0078] The treatment of the remaining groups was as follows: 50 μL of virus inoculum was injected subcutaneously and intramuscularly at the left toe of female mice, and the changes in the paw withdrawal threshold of female mice in the experimental group were observed from the day after intramuscular injection, and the paw withdrawal threshold was measured by a pressure analgesia instrument. The paw withdrawal threshold of female mice began to decline continuously from the second day after intramuscular injection of the virus inoculum, and the paw withdrawal threshold dropped to a lower level and stabilized at this pain threshold level on the 12th day after intramuscular injection of the virus inoculum, indicating that this postherpetic neuralgia model has been successfully established.

[0079] (3) Processing

[0080] The blank group served as the healthy control group and was intramuscularly injected with 0.9 g / 100 mL of normal saline.

[0081] The model group was injected intramuscularly with 0.9 g / 100 mL of normal saline.

[0082] The dextroborneol group was injected intramuscularly with only 75 ng / mL dextroborneol propylene glycol solution; this was used to observe the pain relief of female mice under the action of dextroborneol alone.

[0083] The propylene glycol extract group of Bupleurum was only intramuscularly injected with 75ng / mL propylene glycol extract liquid of Bupleurum to observe the pain relief of female mice under the action of propylene glycol extract of Bupleurum alone.

[0084] The pain relief preparation of Example 1 was intramuscularly injected into the Example 1 group.

[0085] The pain relief preparation of Example 2 was intramuscularly injected into the Example 2 group.

[0086] The pain relief preparation of Example 3 was intramuscularly injected into the Example 3 group.

[0087] The pain relief preparation of Example 4 was intramuscularly injected into the Example 4 group.

[0088] The pain relief preparation of Example 5 was intramuscularly injected into the Example 5 group.

[0089] The pain relief preparation of Example 6 was intramuscularly injected into the Example 6 group.

[0090] The pain relief preparation of the drug control group was intramuscularly injected into the drug control group.

[0091] The specific intramuscular injection volume was referred to Table 1.

[0092] During the intramuscular injection experiment of the virus model, the propylene glycol solution of (+)-camphene was obtained by dissolving (+)-camphene in propylene glycol. The propylene glycol extract liquid of Bupleurum chinense DC. was obtained by dissolving the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture, and in the water-propylene glycol mixture, the volume ratio of water to propylene glycol was 10:1. The pain relief preparation of the drug control group was obtained by changing the propylene glycol extract of Bupleurum chinense DC. in Example 3 to the water extract of Bupleurum chinense DC., and the preparation method of the water extract of Bupleurum chinense DC. was as follows: Bupleurum chinense DC. was ground into a powder of 40 meshes, mixed with deionized water according to the ratio of 1 kg: 8 L, ultrasonically extracted at a power of 400 W for 30 min, filtered through a 50-mesh sieve, and the collected filtrate was freeze-dried at -20 °C to obtain the water extract of Bupleurum chinense DC.

[0093] Table 1 Treatment methods for female mice in different groups

[0094]

[0095] (4) Pain index test

[0096] The mechanical withdrawal threshold of the right hind limb of female mice was measured using a von Frey Filament tactile algesimeter. The stimulation intensity was recorded when female mice showed foot lifting, foot licking or avoidance behavior. Each female mouse was measured 5 times, and the average value of the 3 times after removing the maximum and minimum values was taken as the mechanical withdrawal threshold. The results are shown in Table 2.

[0097] Table 2 Treatment results for female mice in different groups

[0098]

[0099] Herpes zoster is an infectious disease that affects the nerves and skin and is caused by the varicella-zoster virus. Herpes zoster often occurs on the trunk, including the chest, abdomen, and back, mainly causing pain and rashes, without accompanying other special symptoms. Generally, there are no special sequelae after timely treatment. Some patients with herpes zoster can develop postherpetic neuralgia, a type of chronic pain. Patients with postherpetic neuralgia usually experience pain for a long time, which mainly includes neuralgia, stabbing pain, numbness, etc. The nature of the pain is diverse and can be burning, electric shock-like, knife-like, needle-like, or tearing-like. Postherpetic neuralgia affects the normal life of patients. Therefore, it is necessary to develop preparations for relieving postherpetic neuralgia.

[0100] From the results in Table 2, it can be seen that the groups of Example 1 to Example 6 can significantly relieve postherpetic neuralgia. The effects of the drug control group, the (+)-borneol group, and the propylene glycol extract group of Bupleurum chinense DC. in relieving postherpetic neuralgia are significantly lower than those of the groups of Example 1 to Example 6. P <0.05.

[0101] Experiment 2. Intramuscular injection experiment for acute pain model

[0102] (1) Experimental animals

[0103] SD rats: body weight 250 ± 10.2 g.

[0104] (2) Model establishment

[0105] 132 SD rats were randomly divided into 11 groups, with 12 rats in each group; the names of the 11 groups were the blank group, the model group, the (+)-borneol group, the propylene glycol extract group of Bupleurum chinense DC., the group of Example 1, the group of Example 2, the group of Example 3, the group of Example 4, the group of Example 5, the group of Example 6, and the drug control group.

[0106] 6 hours before model establishment in SD rats, food was withheld, and water was withheld 1 hour before model establishment. The SD rats were placed in a 1 L transparent glass container with cotton balls soaked in isoflurane liquid to make the SD rats lose consciousness. A 1 cm long incision was made from 0.5 cm proximal to the sole of the foot of the SD rats towards the toes, the skin was incised, and then the sole muscle was picked up with ophthalmic forceps and cut longitudinally while keeping the origin, insertion, and attachment of the muscle intact. After pressing to stop bleeding, the skin was sutured with a fine needle to complete the establishment of the acute pain model.

[0107] (3) Treatment

[0108] The blank group served as the healthy control group and was intramuscularly injected with normal saline at a concentration of 0.9 g / 100 mL.

[0109] The model group was intramuscularly injected with normal saline at a concentration of 0.9 g / 100 mL.

[0110] The (+)-campherenol group was only intramuscularly injected with a propylene glycol solution of 75 ng / mL (+)-campherenol.

[0111] The (+)-campherenol group was only intramuscularly injected with a propylene glycol extract liquid of 75 ng / mL Bupleuri Radix.

[0112] The group of Example 1 was intramuscularly injected with the pain relief preparation of Example 1.

[0113] The group of Example 2 was intramuscularly injected with the pain relief preparation of Example 2.

[0114] The group of Example 3 was intramuscularly injected with the pain relief preparation of Example 3.

[0115] The group of Example 4 was intramuscularly injected with the pain relief preparation of Example 4.

[0116] The group of Example 5 was intramuscularly injected with the pain relief preparation of Example 5.

[0117] The group of Example 6 was intramuscularly injected with the pain relief preparation of Example 6.

[0118] The drug control group was intramuscularly injected with the pain relief preparation of the drug control group.

[0119] Among them, the propylene glycol solution of (+)-campherenol was obtained by dissolving it in propylene glycol. The propylene glycol extract liquid of Bupleuri Radix was obtained by dissolving the propylene glycol extract of Bupleuri Radix in a water-propylene glycol mixture, and in the water-propylene glycol mixture, the volume ratio of water to propylene glycol was 10:1. The pain relief preparation of the drug control group was obtained by changing the propylene glycol extract of Bupleuri Radix in Example 3 to the water extract of Bupleuri Radix. The preparation method of the water extract of Bupleuri Radix was as follows: Bupleuri Radix was ground into a powder of 40 meshes, mixed with deionized water according to the ratio of 1 kg: 8 L, ultrasonically extracted at a power of 400 W for 30 min, filtered through a 50-mesh sieve, and the collected filtrate was freeze-dried at -20 °C to obtain the water extract of Bupleuri Radix.

[0120] The specific intramuscular injection amount was referred to Table 3.

[0121] Table 3 Treatment methods of SD rats in different groups

[0122]

[0123] (4) Pain index test

[0124] Referring to the method of Experiment 1 above, the mechanical stimulation paw withdrawal threshold was tested, and the results were shown in Table 4.

[0125] Table 4 Treatment results of SD rats in different groups

[0126]

[0127] Relieving acute pain is of great significance in many aspects, which is reflected in multiple levels such as physiology, psychology, disease treatment, and social economy. For example, it can avoid physiological dysfunction, promote wound healing, relieve anxiety and fear, improve sleep quality, enhance patient compliance, and reduce the occupation of medical resources, etc.

[0128] As can be seen from the results in Table 4, the groups of Example 1 to Example 6 can significantly relieve acute pain, while the effects of relieving acute pain in the drug control group, the (+)-borneol group, and the propylene glycol extract group of Bupleurum chinense DC. are significantly lower than those of the groups of Example 1 to Example 6. P <0.05.

[0129] It should be noted that when the present invention involves numerical ranges, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the adopted step methods are the same as those in the examples, in order to avoid redundancy, the present invention describes the preferred embodiments. Although the preferred embodiments of the present invention have been described, once those skilled in the art know the creative concept of the present invention, they can make additional changes and modifications to these embodiments, and these changes and modifications all fall within the scope of the present invention.

[0130] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. If these modifications and variations of the present invention belong to the scope of equivalent technologies of the present invention, the present invention also intends to include these changes and deformations.

Claims

1. Use of a pain relief preparation in the manufacture of a medicament for relieving postherpetic neuralgia, characterized in that, The pain relief preparation consists of (+)-camphene, the propylene glycol extract of Bupleurum chinense DC., and pharmaceutically acceptable excipients; wherein, the mass ratio of the (+)-camphene to the propylene glycol extract of Bupleurum chinense DC. is 1 - 2.5:1; The propylene glycol extract of Bupleurum chinense DC. is prepared by the following method: Grind Bupleurum chinense DC. into powder, mix it with propylene glycol, perform ultrasonic extraction, filter, collect the filtrate, and dry it to obtain the propylene glycol extract of Bupleurum chinense DC.

2. Use of the pain relief preparation according to claim 1 in the preparation of a drug for relieving postherpetic neuralgia, characterized in that, The mass ratio of the (+)-camphene to the propylene glycol extract of Bupleurum chinense DC. is 2:

1.

3. Use of the pain relief preparation according to claim 1 in the preparation of a drug for relieving postherpetic neuralgia, characterized in that, The conditions of the ultrasonic extraction are ultrasonic extraction for 30 min at a power of 400 W.

4. Use of the pain relief preparation according to claim 3 in the preparation of a drug for relieving postherpetic neuralgia, characterized in that, The pharmaceutically acceptable excipients are any of the following situations: (a) The pharmaceutically acceptable excipients are a combination of propylene glycol and water; (b) The pharmaceutically acceptable excipients are propylene glycol; (c) The pharmaceutically acceptable excipients are a combination of hydroxypropyl-β-cyclodextrin, propylene glycol, and water.

5. Use of the pain relief preparation according to claim 1 in the preparation of a medicament for relieving postherpetic neuralgia, characterized in that, The concentration of (+)-camphene in the pain relief preparation is 60 ng / mL - 80 ng / mL.

6. Use of the pain relief preparation according to claim 1 in the preparation of a drug for relieving postherpetic neuralgia, characterized in that, The concentration of (+)-camphene in the pain relief preparation is 75 ng / mL.

7. Use of the pain relief preparation according to claim 1 in the preparation of a drug for relieving postherpetic neuralgia, characterized in that, The preparation method of the pain relief preparation includes: Mix the (+)-camphene, the propylene glycol extract of Bupleurum chinense DC., and the pharmaceutically acceptable excipients, and the obtained mixture is the pain relief preparation.

8. Use of the pain relief preparation according to claim 4 in the preparation of a drug for relieving postherpetic neuralgia, characterized in that, The preparation method of the pain relief preparation includes: Dissolve (+)-camphene in propylene glycol to obtain a (+)-camphene liquid; Dissolve the propylene glycol extract of Bupleurum chinense DC. in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of Bupleurum chinense DC.; Mix the (+)-camphene liquid with the propylene glycol extract liquid of Bupleurum chinense DC. to obtain the pain relief preparation.

9. Use of the pain relief preparation according to claim 1 in the preparation of a drug for relieving postherpetic neuralgia, characterized in that, The drug for relieving postherpetic neuralgia is a drug for relieving the pain caused by varicella-zoster virus.

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