Pain relieving preparation as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pain relieving preparations, and particularly relates to a pain relieving preparation as well as a preparation method and application thereof. The pain relieving preparation is composed of dextroborneol, a propylene glycol extract of radix bupleuri and pharmaceutically acceptable auxiliary materials, the mass ratio of dextroborneol to the propylene glycol extract of radix bupleuri is (1-2.5): 1, and the propylene glycol extract of radix bupleuri is prepared by the following steps: grinding radix bupleuri into powder, mixing the powder with propylene glycol, performing ultrasonic extraction, filtering, collecting filtrate, and drying to obtain the dextroborneol-propylene glycol extract of radix bupleuri. The propylene glycol extract of the radix bupleuri is obtained. The invention further provides a preparation method of the pain relieving preparation, application of the pain relieving preparation in relieving acute pain and post-herpes zoster neuralgia is proved, and the variety of the pain relieving preparation is expanded.

Description

Technical Field

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

[0002] Many diseases are accompanied by symptoms of pain, such as bacterial infection, viral infection, etc. Pain will affect the patient's normal life, so it is necessary to relieve pain.

[0003] In the prior art, the means of relieving pain mainly include: taking ibuprofen, acetaminophen and other preparations, using lidocaine patches for local anesthesia, pulsed radiofrequency treatment, and short-term spinal cord stimulation. Among them, preparations for relief are more convenient and have a wider range of applications. For example, the preparations that can be 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 analgesia; (3) central nervous system preparations: such as gabapentin capsules, pregabalin capsules, etc., which can Mildly inhibit the central nervous system and relieve itching and other discomfort symptoms; (4) Tricyclic antidepressant preparations: such as amitriptyline hydrochloride tablets, imipramine hydrochloride tablets, etc. Patients with postherpetic neuralgia may experience anxiety, depression and other symptoms due to long-term pain, which may lead to the perception of increased pain. At this time, the above preparations can be used for treatment; (5) Chinese medicine preparations for promoting blood circulation and regulating qi, such as Chaihu Shugan San, Taohong Siwu Tang, Xuefu Zhuyu Tang, etc., can help promote blood circulation and remove blood stasis, and then relieve pain symptoms. However, due to the differences in the physical constitution of different patients, their sensitivity and resistance to the analgesic preparations in the existing technology 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 and a preparation method and application thereof. The pain relief preparation can relieve acute pain and postherpetic neuralgia.

[0005] The object of the present invention is to provide a pain relief preparation, which is composed of borneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients, wherein the mass ratio of borneol to the propylene glycol extract of bupleurum is 1-2.5:1, and the propylene glycol extract of bupleurum is prepared according to the following method: grinding bupleurum into powder and mixing with propylene glycol, ultrasonic extraction, filtering, collecting the filtrate, and drying to obtain the propylene glycol extract of bupleurum.

[0006] According to the research results of the present invention, after dextroborneol is combined with the propylene glycol extract of Bupleurum, it is matched with pharmaceutically acceptable excipients to form a mixture preparation. In relieving acute pain or postherpetic neuralgia, dextroborneol and the propylene glycol extract of Bupleurum have a synergistic analgesic effect. In addition, in the pain relief preparation of the present invention, dextroborneol is mainly used to relieve pain related to nerve damage, which can regulate the body's immune function and inhibit pain transmission; the propylene glycol extract of Bupleurum contains saikosaponins, volatile oils and sterols, which can activate blood circulation and reduce the transmission of pain signals; therefore, after dextroborneol is combined with the propylene glycol extract of Bupleurum, the effect of reducing pain signal transmission is enhanced, acute pain can be relieved, and postherpetic neuralgia is also significantly relieved.

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

[0008] In addition, after bupleurum is ground into powder, the particle size becomes smaller and the surface area increases, allowing for more complete contact with the solvent propylene glycol. With the assistance of ultrasonic extraction, bupleurum saponins, volatile oils and sterols can be dissolved in propylene glycol. After filtering, collecting the filtrate and drying, a propylene glycol extract of bupleurum rich in bupleurum saponins, volatile oils and sterols can be obtained.

[0009] Preferably, in the pain relief preparation, the mass ratio of the dextroborneol to the propylene glycol extract of Bupleurum is 2:1, and the pain relief effect is better.

[0010] Preferably, in the pain relief preparation, the ultrasonic extraction is performed for 30 min at a power of 400 W. Under the ultrasonic condition, the solubility of saikosaponin, volatile oil and sterol in propylene glycol is high.

[0011] Preferably, the specific preparation method of the propylene glycol extract of Bupleurum is as follows: grind Bupleurum into 40 mesh powder, mix with propylene glycol at a ratio of 1kg: 8L, ultrasonically extract for 30 minutes at 400W power, filter with a 50 mesh sieve, and collect the filtrate to obtain the propylene glycol extract of Bupleurum.

[0012] Preferably, the pain relief preparation, the pharmaceutically acceptable excipients include at least any one of the following: (a) The pharmaceutically acceptable excipient is a combination of propylene glycol and water; (b) The pharmaceutically acceptable excipient is propylene glycol; (c) A combination of pharmaceutically acceptable excipients: hydroxypropyl β-cyclodextrin, propylene glycol and water.

[0013] It should be noted that the "combination" mentioned in the pharmaceutically acceptable excipients refers to raw materials using multiple pharmaceutically acceptable excipients, and these raw materials can be mixed before use or used separately.

[0014] Preferably, in the pain relief preparation, the concentration of dextroborneol in the pain relief preparation is 60 ng / mL to 80 ng / mL.

[0015] Preferably, in the pain relief preparation, the concentration of dextroborneol in the pain relief preparation is 75 ng / mL.

[0016] The invention provides a method for preparing a pain relief preparation. Dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable auxiliary materials are mixed to obtain a mixture which is the pain relief preparation.

[0017] Preferably, when the pharmaceutically acceptable excipient is a combination of propylene glycol and water; the preparation method of the pain relief preparation comprises: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of bupleurum; mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain a pain relief preparation suitable for intramuscular injection.

[0018] Preferably, when the pharmaceutically acceptable excipient is propylene glycol; the preparation method of the pain relief preparation comprises: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in propylene glycol to obtain the propylene glycol extract liquid of bupleurum; mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relief preparation suitable for nasal drops.

[0019] Preferably, the pharmaceutically acceptable excipient is a combination of excipients hydroxypropyl β-cyclodextrin, propylene glycol and water; the preparation method of the pain relief preparation comprises: encapsulating dextroborneol in the excipient hydroxypropyl β-cyclodextrin to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixed liquid to obtain a propylene glycol extract liquid of bupleurum; mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain a pain relief preparation suitable for intramuscular injection.

[0020] The present invention provides an application of a pain relief preparation, wherein the application refers to relieving acute pain or relieving postherpetic neuralgia.

[0021] Preferably, in the application of the pain relief preparation, the postherpetic neuralgia is pain caused by varicella-zoster virus.

[0022] Compared with the prior art, the present invention has the following beneficial effects: The pain relief preparation of the present invention is composed of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 1-2.5:1; the preparation method of the propylene glycol extract of bupleurum is as follows: grinding bupleurum into powder, mixing with propylene glycol, ultrasonic extraction, filtering, collecting the filtrate, and drying to obtain the propylene glycol extract of bupleurum. Dextroborneol and the propylene glycol extract of bupleurum are combined and then matched with pharmaceutically acceptable excipients to form a mixture preparation. In the pain relief preparation of the present invention, dextroborneol and the propylene glycol extract of bupleurum have a synergistic analgesic effect in relieving acute pain or postherpetic neuralgia. DETAILED DESCRIPTION

[0023] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention is further described below in conjunction with specific embodiments.

[0024] In the description of the present invention, unless otherwise specified, all reagents used are commercially available and all methods used are conventional techniques in the art.

[0025] In the following examples and experimental processes, borneol was purchased from Jiangxi Linke Borneol Technology Co., Ltd. It is made by extracting and processing fresh branches and leaves of camphor, a plant of the Lauraceae family, with a borneol content of ≥96% and a packaging specification of 500 g / bag. According to medical research results, borneol has analgesic, anti-inflammatory and sleep-improving effects.

[0026] Bupleurum was purchased from a Chinese herbal medicine store. According to medical research results, Bupleurum has the effects of relieving fever and inflammation, soothing the liver and relieving depression, raising yang energy, and reconciling the exterior and interior.

[0027] In the pain relief preparation of the present invention, the substances that relieve pain are dextroborneol and 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 pain relief refers to acute pain or relief of postherpetic neuralgia.

[0028] When the pharmaceutically acceptable excipient is a combination of propylene glycol and water; the preparation method of the pain relief preparation includes: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixed liquid to obtain a propylene glycol extract liquid of bupleurum; mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain a pain relief preparation suitable for intramuscular injection. The volume ratio of water to propylene glycol in the water-propylene glycol mixed liquid is 10:1.

[0029] When the pharmaceutically acceptable excipient is propylene glycol; the preparation method of the pain relief preparation includes: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in propylene glycol to obtain the propylene glycol extract liquid of bupleurum; mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relief preparation suitable for nasal drops.

[0030] When the pharmaceutically acceptable excipient is a combination of excipients hydroxypropyl β-cyclodextrin, propylene glycol and water; the preparation method of the pain relief preparation includes: encapsulating dextroborneol in the excipient hydroxypropyl β-cyclodextrin to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixed liquid to obtain a propylene glycol extract liquid of bupleurum; mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain a pain relief preparation suitable for intramuscular injection. The volume ratio of water to propylene glycol in the water-propylene glycol mixed liquid is 10:1.

[0031] The embodiments of the present invention and the corresponding pain relief effects are described below using the dosage form of intramuscular injection and related animal experiments.

[0032] Example 1 A pain relief preparation consists of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 1:1.

[0033] The preparation method of the propylene glycol extract of Bupleurum is as follows: grind Bupleurum into 40 mesh powder, mix with propylene glycol at a ratio of 1 kg: 8 L, ultrasonically extract for 30 minutes at 400 W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the propylene glycol extract of Bupleurum.

[0034] The pharmaceutically acceptable excipient is a combination of propylene glycol and water.

[0035] The preparation method of the pain relief preparation is as follows: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of bupleurum; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; taking the mass ratio of dextroborneol to the propylene glycol extract of bupleurum as 1:1, preparing dextroborneol liquid and propylene glycol extract liquid of bupleurum, and then mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relief preparation, and the dextroborneol concentration in the pain relief preparation is 75 ng / mL.

[0036] Example 2 A pain relief preparation consists of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 1.5:1.

[0037] The preparation method of the propylene glycol extract of Bupleurum is as follows: grind Bupleurum into 40 mesh powder, mix with propylene glycol at a ratio of 1 kg: 8 L, ultrasonically extract for 30 minutes at 400 W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the propylene glycol extract of Bupleurum.

[0038] The pharmaceutically acceptable excipient is a combination of propylene glycol and water.

[0039] The preparation method of the pain relief preparation is as follows: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of bupleurum; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; based on the mass ratio of dextroborneol to the propylene glycol extract of bupleurum being 1.5:1, dextroborneol liquid and propylene glycol extract liquid of bupleurum are prepared, and then the dextroborneol liquid and the propylene glycol extract liquid of bupleurum are mixed to obtain the pain relief preparation, and the dextroborneol concentration in the pain relief preparation is 75 ng / mL.

[0040] Example 3 A pain relief preparation consists of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 2:1.

[0041] The preparation method of the propylene glycol extract of Bupleurum is as follows: grind Bupleurum into 40 mesh powder, mix with propylene glycol at a ratio of 1 kg: 8 L, ultrasonically extract for 30 minutes at 400 W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the propylene glycol extract of Bupleurum.

[0042] The pharmaceutically acceptable excipient is a combination of propylene glycol and water.

[0043] The preparation method of the pain relief preparation is as follows: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of bupleurum; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; preparing dextroborneol liquid and propylene glycol extract liquid of bupleurum at a mass ratio of dextroborneol to propylene glycol extract of bupleurum of 2:1, and then mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relief preparation, and the dextroborneol concentration in the pain relief preparation is 75 ng / mL.

[0044] Example 4 A pain relief preparation consists of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 2.5:1.

[0045] The preparation method of the propylene glycol extract of Bupleurum is as follows: grind Bupleurum into 40 mesh powder, mix with propylene glycol at a ratio of 1 kg: 8 L, ultrasonically extract for 30 minutes at 400 W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the propylene glycol extract of Bupleurum.

[0046] The pharmaceutically acceptable excipient is a combination of propylene glycol and water.

[0047] The preparation method of the pain relief preparation is as follows: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of bupleurum; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; based on the mass ratio of dextroborneol to the propylene glycol extract of bupleurum being 2.5:1, dextroborneol liquid and propylene glycol extract liquid of bupleurum are prepared, and then the dextroborneol liquid and the propylene glycol extract liquid of bupleurum are mixed to obtain the pain relief preparation, and the dextroborneol concentration in the pain relief preparation is 75 ng / mL.

[0048] Example 5 A pain relief preparation consists of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 2:1.

[0049] The preparation method of the propylene glycol extract of Bupleurum is as follows: grind Bupleurum into 40 mesh powder, mix with propylene glycol at a ratio of 1 kg: 8 L, ultrasonically extract for 30 minutes at 400 W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the propylene glycol extract of Bupleurum.

[0050] The pharmaceutically acceptable excipient is a combination of propylene glycol and water.

[0051] The preparation method of the pain relief preparation is as follows: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of bupleurum; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; preparing dextroborneol liquid and propylene glycol extract liquid of bupleurum at a mass ratio of dextroborneol to propylene glycol extract of bupleurum of 2:1, and then mixing the dextroborneol liquid with the propylene glycol extract liquid of bupleurum to obtain the pain relief preparation, and the dextroborneol concentration in the pain relief preparation is 60 ng / mL.

[0052] Example 6 A pain relief preparation consists of dextroborneol, a propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; wherein the mass ratio of dextroborneol to the propylene glycol extract of bupleurum is 2:1.

[0053] The preparation method of the propylene glycol extract of Bupleurum is as follows: grind Bupleurum into 40 mesh powder, mix with propylene glycol at a ratio of 1 kg: 8 L, ultrasonically extract for 30 minutes at 400 W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the propylene glycol extract of Bupleurum.

[0054] The pharmaceutically acceptable excipient is a combination of propylene glycol and water.

[0055] The preparation method of the pain relief preparation is as follows: dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture to obtain a propylene glycol extract liquid of bupleurum; the volume ratio of water to propylene glycol in the water-propylene glycol mixture is 10:1; based on the mass ratio of dextroborneol to the propylene glycol extract of bupleurum being 2:1, dextroborneol liquid and propylene glycol extract liquid of bupleurum are prepared, and then the dextroborneol liquid and the propylene glycol extract liquid of bupleurum are mixed to obtain the pain relief preparation, and the dextroborneol concentration in the pain relief preparation is 80 ng / mL.

[0056] The difference between Examples 1 to 4 is that the mass ratios of borneol and the propylene glycol extract of Bupleurum are different. In Example 1, the mass ratio of borneol to the propylene glycol extract of Bupleurum is 1:1; in Example 2, the mass ratio of borneol to the propylene glycol extract of Bupleurum is 1.5:1; in Example 3, the mass ratio of borneol to the propylene glycol extract of Bupleurum is 2:1; in Example 4, the mass ratio of borneol to the propylene glycol extract of Bupleurum is 2.5:1. The difference between Examples 3, 5 and 6 is that the concentrations of borneol in the pain relief preparation are 75 ng / mL, 60 ng / mL and 80 ng / mL, respectively.

[0057] The dosage forms of Examples 1 to 6 are all intramuscular injections, and the methods of use are all intramuscular injections.

[0058] The analgesic effects of the pain relief preparations of Examples 1 to 6 are discussed below.

[0059] Experiment 1: Intramuscular injection experiment of virus model (1) Main experimental materials and animals CV-1 cells: purchased from Shanghai Yaji Biotechnology Co., Ltd., the brand is Yaji Bio.

[0060] Complete medium: DMEM / F12.

[0061] Female mice: body weight 30±0.2g.

[0062] (2) Grouping and modeling 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 / cm2 , 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.

[0063] 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.

[0064] The treatment of female mice in the blank group was as follows: 50 μL of normal saline was injected subcutaneously into the left toe.

[0065] 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.

[0066] (3) Processing The blank group served as the healthy control group and was intramuscularly injected with 0.9 g / 100 mL of normal saline.

[0067] The model group was injected intramuscularly with normal saline at a concentration of 0.9 g / 100 mL.

[0068] 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.

[0069] 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.

[0070] The pain relief preparation of Example 1 was injected intramuscularly in Group 1.

[0071] The pain relief preparation of Example 2 was injected intramuscularly in Group 2.

[0072] The pain relief preparation of Example 3 was injected intramuscularly in Group 3.

[0073] Group 4 of Example 4 was intramuscularly injected with the pain relief preparation of Example 4.

[0074] The pain relief preparation of Example 5 was injected intramuscularly in Group 5.

[0075] The pain relief preparation of Example 6 was injected intramuscularly in Group 6.

[0076] The drug control group was injected intramuscularly with the pain relief preparation of the drug control group.

[0077] Please refer to Table 1 for specific intramuscular injection doses.

[0078] During the virus model intramuscular injection experiment, the propylene glycol solution of dextroborneol was obtained by dissolving dextroborneol in propylene glycol. The propylene glycol extract liquid of Bupleurum was obtained by dissolving the propylene glycol extract of Bupleurum in a water-propylene glycol mixture, and the volume ratio of water to propylene glycol in the water-propylene glycol mixture was 10:1. The pain relief preparation of the drug control group was obtained by replacing the propylene glycol extract of Bupleurum in Example 3 with the water extract of Bupleurum, and the preparation method of the water extract of Bupleurum was as follows: Grind Bupleurum into 40 mesh powder, mix with deionized water at a ratio of 1kg: 8L, ultrasonically extract for 30min at 400W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the water extract of Bupleurum.

[0079] Table 1 Treatment methods of female mice in different groups

[0080] (4) Pain index test The mechanical stimulation paw withdrawal threshold of the right hind limb of female mice was measured using a Von Frey Filament tactile analgesia instrument. The stimulation intensity when the female mice lifted their paws, licked their paws, or avoided the paws was recorded. Each female mouse was measured 5 times, and the average of the 3 times after removing the maximum and minimum values ​​was taken as the mechanical stimulation paw withdrawal threshold. The results are shown in Table 2.

[0081] Table 2 Treatment results of female mice in different groups

[0082] Shingles is an infectious disease that affects the nerves and skin and is caused by the varicella-zoster virus. Shingles often occurs on the trunk, including the chest, abdomen and back, mainly causing pain and rash, without other special symptoms, and generally without special sequelae after timely treatment. Some patients with shingles may develop chronic pain called postherpetic neuralgia. Patients with postherpetic neuralgia usually experience prolonged pain, which mainly includes neuralgia, tingling, numbness, etc. The nature of the pain varies and may be burning, electric shock, knife-like, needle-like or tearing. Postherpetic neuralgia can affect the patient's normal life, so it is necessary to develop preparations to relieve postherpetic neuralgia.

[0083] From the results in Table 2, it can be seen that Example 1 to Example 6 can significantly relieve postherpetic neuralgia. However, the effects of the drug control group, the borneol group, and the propylene glycol extract of Bupleurum chinense group on relieving postherpetic neuralgia are significantly lower than those of Example 1 to Example 6. P <0.05.

[0084] Experiment 2: Intramuscular injection experiment of acute pain model (1) Experimental animals SD rats: body weight 250±10.2 g.

[0085] (2) Modeling 132 SD rats were randomly divided into 11 groups, with 12 rats 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.

[0086] The SD rats were fasted for 6 hours and water for 1 hour before modeling. The SD rats were placed in a 1L transparent glass container soaked with isoflurane liquid cotton balls to make them unconscious. A 1cm long incision was made from 0.5cm proximal to the sole of the SD rat to the toe, the skin was cut open, and then the sole muscle was picked up with ophthalmic forceps and cut longitudinally, while keeping the muscle's origin, insertion and attachment intact. After pressing to stop bleeding, the skin was sutured with a fine needle to complete the modeling of the acute pain model.

[0087] (3) Processing The blank group served as the healthy control group and was intramuscularly injected with 0.9 g / 100 mL of normal saline.

[0088] The model group was injected intramuscularly with normal saline at a concentration of 0.9 g / 100 mL.

[0089] The dextroborneol group was injected intramuscularly with 75 ng / mL dextroborneol in propylene glycol solution.

[0090] The dextroborneol group was only intramuscularly injected with 75 ng / mL propylene glycol extract of Bupleurum chinense.

[0091] The pain relief preparation of Example 1 was injected intramuscularly in Group 1.

[0092] The pain relief preparation of Example 2 was injected intramuscularly in Group 2.

[0093] The pain relief preparation of Example 3 was injected intramuscularly in Group 3.

[0094] Group 4 of Example 4 was intramuscularly injected with the pain relief preparation of Example 4.

[0095] The pain relief preparation of Example 5 was injected intramuscularly in Group 5.

[0096] The pain relief preparation of Example 6 was injected intramuscularly in Group 6.

[0097] The drug control group was injected intramuscularly with the pain relief preparation of the drug control group.

[0098] Wherein, the propylene glycol solution of dexamethicone is obtained by dissolving it in propylene glycol. The propylene glycol extract liquid of bupleurum is obtained by dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixture, and in the water-propylene glycol mixture, the volume ratio of water to propylene glycol is 10:1. The pain relief preparation of the drug control group is to replace the propylene glycol extract of bupleurum in Example 3 with the water extract of bupleurum, and the preparation method of the water extract of bupleurum is as follows: grind bupleurum into 40 mesh powder, mix with deionized water at a ratio of 1kg: 8L, ultrasonically extract for 30min at 400W power, filter with a 50 mesh sieve, and freeze-dry the collected filtrate at -20°C to obtain the water extract of bupleurum.

[0099] Please refer to Table 3 for specific intramuscular injection doses.

[0100] Table 3 Treatment methods of SD rats in different groups

[0101] (4) Pain index test The mechanical stimulation paw withdrawal threshold was tested according to the method of Experiment 1 above. The results are shown in Table 4.

[0102] Table 4 Treatment results of SD rats in different groups

[0103] Relieving acute pain is of great significance in many aspects, including physiology, psychology, disease treatment and socio-economic aspects. For example, it can avoid physiological dysfunction, promote wound healing, reduce anxiety and fear, improve sleep quality, improve patient compliance and reduce the use of medical resources.

[0104] From the results in Table 4, it can be seen that the acute pain can be significantly relieved in the Example 1 to Example 6 groups, while the acute pain relief effects of the drug control group, the borneol group, and the propylene glycol extract of Bupleurum chinense group were significantly lower than those of the Example 1 to Example 6 groups. P <0.05.

[0105] It should be noted that when the present invention involves a numerical range, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as those in the embodiments, in order to avoid redundancy, the present invention describes a preferred embodiment. Although the preferred embodiments of the present invention have been described, once those skilled in the art know the inventive concept of the present invention, they can make other changes and modifications to these embodiments, and these changes and modifications all fall within the scope of the present invention.

[0106] 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 fall within the scope of the equivalent technology of the present invention, the present invention is also intended to include these modifications and variations.

Claims

1. A pain relief preparation, characterized in that The invention is composed of dextroborneol, propylene glycol extract of bupleurum and pharmaceutically acceptable excipients; Wherein, the mass ratio of the dextroborneol to the propylene glycol extract of bupleurum is 1-2.5:1; The propylene glycol extract of Bupleurum chinense is prepared according to the following method: The bupleurum root is ground into powder and then mixed with propylene glycol, subjected to ultrasonic extraction, filtered, the filtrate is collected, and dried to obtain the propylene glycol extract of bupleurum root.

2. The pain relief preparation according to claim 1, characterized in that The mass ratio of the dextroborneol to the propylene glycol extract of bupleurum is 2:

1.

3. The pain relief preparation according to claim 1, characterized in that The ultrasonic extraction was performed under a power of 400 W for 30 min.

4. The pain relief preparation according to claim 3, characterized in that The pharmaceutically acceptable excipients include at least any of the following: (a) The pharmaceutically acceptable excipient is a combination of propylene glycol and water; (b) The pharmaceutically acceptable excipient is propylene glycol; (c) A combination of pharmaceutically acceptable excipients: hydroxypropyl β-cyclodextrin, propylene glycol and water.

5. The pain relief preparation according to claim 1, characterized in that The concentration of dextroborneol in the pain relief preparation is 60 ng / mL to 80 ng / mL.

6. The pain relief preparation according to claim 1, characterized in that The concentration of dextroborneol in the pain relief formulation is 75 ng / mL.

7. A method for preparing a pain relief preparation, characterized in that: The pain relief preparation is the pain relief preparation of claim 1; The preparation method comprises: The dextroborneol, the propylene glycol extract of bupleurum and pharmaceutically acceptable excipients are mixed to obtain a mixture that is a pain relief preparation.

8. A method for preparing a pain relief preparation, characterized in that: The pain relief preparation is the pain relief preparation of claim 4; The preparation method comprises: Dissolving dextroborneol in propylene glycol to obtain dextroborneol liquid; dissolving the propylene glycol extract of bupleurum in a water-propylene glycol mixed solution to obtain a propylene glycol extract liquid of bupleurum; The dextroborneol liquid is mixed with the propylene glycol extract liquid of bupleurum to obtain a pain relief preparation.

9. Use of a pain relief preparation, characterized in that: The application is to prepare the pain relief preparation according to claim 1 into a drug for relieving acute pain or relieving postherpetic neuralgia.

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

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