Traditional Chinese medicine composition for treating herpes zoster neuralgia and preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating herpes zoster neuralgia and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicine, the traditional Chinese medicine composition for treating herpes zoster neuralgia is composed of scalded peach kernel, safflower, angelica sinensis, radix rehmanniae recen, ligusticum wallichii, radix paeoniae rubra, radix cyathulae, platycodon grandiflorum, radix bupleuri, fructus aurantii stir-fried with bran, vinegar-processed corydalis tuber, stir-fried spina date seed, vine of multiflower knotweed and liquorice. The traditional Chinese medicine composition has the effects of promoting qi to activate blood, dispersing blood stasis to relieve pain and calming the heart and tranquilizing the mind, is clinically used for treating herpes zoster neuralgia and animal pharmacological experiments show that the traditional Chinese medicine composition is remarkable in curative effect and free of untoward effects, realizes organic combination of macroscopic regulation and microcosmic targeting on treatment of herpes zoster neuralgia, and has a wide application prospect. When the traditional Chinese medicine composition for treating herpes zoster neuralgia is used as a decoction, the decoction method is simple, and the warm taking effect is good; when the traditional Chinese medicine composition is used as granules, through strict optimization of preparation process parameters, the granules are good in formability, the process parameters are stable and reliable during actual production, and the traditional Chinese medicine composition has the advantages of convenience in carrying and taking, stable curative effect and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for treating herpetic neuralgia, and a preparation method and application thereof. Background Art

[0002] Herpes zoster (HZ) is one of the more common diseases in clinical practice. According to the latest monitoring data from the Centers for Disease Control and Prevention in the United States, its incidence has been increasing in recent years and is becoming younger. In addition to the characteristic unilateral clustered blisters on the skin, it is usually accompanied by obvious pathological neuralgia, namely herpetic zoster-related neuralgia (ZRN). According to the course of the disease pain, it is mainly divided into acute herpetic neuralgia (AHN), subacute herpetic neuralgia (SHN) and postherpetic neuralgia (PHN). If ZRN is not promptly, effectively and reasonably intervened in the early stage, the patient is likely to develop PHN. Data show that about 29.8% of HZ patients will develop into PHN, and because of the persistence of pain and the difficulty in curing it, patients will suffer from insomnia, anxiety, depression, etc., which seriously damages the physical and mental health of patients, affects the quality of daily life, and brings great medical care and economic burdens to individuals and society.

[0003] The main methods of modern medicine for treating SHN and PHN are oral medications and minimally invasive surgery. Although they can relieve pain, they do not improve sleep well, have a long treatment cycle, and long-term oral analgesics are prone to adverse reactions.

[0004] Traditional Chinese medicine has long known about herpes zoster neuralgia. It believes that this disease is mostly caused by herpes zoster entering the collaterals over a long period of time, dampness and heat and other toxic evils lurking in the body for a long time, which block the collaterals to varying degrees, malfunction of qi and blood circulation, and blood stasis in the collaterals, resulting in pain due to obstruction. Treatment is mainly based on prescriptions for promoting blood circulation and removing blood stasis, unblocking collaterals and relieving pain, and the dosage is adjusted according to the symptoms. Since traditional Chinese medicine often uses natural Chinese medicine as raw materials, it is inexpensive and can achieve the effect of improving drug efficacy and not producing toxic side effects for a relatively long time through reasonable compatibility and selection of medicinal flavors, and has good treatment prospects.

[0005] Therefore, it is of great significance to develop a Chinese medicine composition for treating herpes zoster neuralgia that can effectively treat herpes zoster neuralgia, accelerate the recovery process of the disease, and reduce the toxic and side effects of Western medicines. Summary of the invention

[0006] The purpose of the present invention is to provide a Chinese medicine composition for treating herpes zoster neuralgia and its preparation method and application, so as to solve the following technical problems:

[0007] How to effectively treat herpes zoster neuralgia by using a Chinese medicine composition for treating herpes zoster neuralgia.

[0008] The purpose of the present invention can be achieved through the following technical solutions:

[0009] In a first aspect, the present invention discloses a Chinese medicine composition for treating herpes zoster neuralgia, which is composed of the following components in parts by weight:

[0010] 10-20 parts of stewed peach kernels, 10-20 parts of safflower, 10-20 parts of angelica, 15-30 parts of raw rehmannia, 5-20 parts of chuanxiong, 5-20 parts of red peony root, 10-20 parts of chuanxiong, 5-10 parts of platycodon, 5-10 parts of bupleurum, 5-10 parts of stir-fried aurantium with bran, 15-30 parts of vinegar corydalis, 15-30 parts of stir-fried spiny jujube kernels, 15-30 parts of Polygonum multiflorum, and 5-10 parts of liquorice.

[0011] In a second aspect, the present invention discloses a method for preparing the above-mentioned Chinese medicine composition for treating herpetic neuralgia, wherein the Chinese medicine composition for treating herpetic neuralgia is prepared into a decoction, comprising the following steps:

[0012] Step 1: prepare and mix the raw material components according to the proportion, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep for 1 hour after boiling, and filter to obtain filter material 1 and filtrate 1;

[0013] Step 2: add 8 times the amount of water to filter material 1, then heat and boil, keep boiling for 1 hour, filter to obtain filter material 2 and filtrate 2, combine filtrate 1 and filtrate 2 to obtain a Chinese medicine composition decoction for treating herpes zoster neuralgia.

[0014] In a third aspect, the present invention discloses a method for preparing the above-mentioned Chinese medicine composition for treating herpetic neuralgia, wherein the Chinese medicine composition for treating herpetic neuralgia is prepared into granules, comprising the following steps:

[0015] Step 1: prepare and mix the raw material components according to the proportion, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep for 1 hour after boiling, and filter to obtain filter material 1 and filtrate 1;

[0016] Step 2, adding 8 times the amount of water to the filter material 1, then heating and boiling, keeping it for 1 hour after boiling, filtering to obtain the filter material 2 and the filtrate 2, combining the filtrate 1 and the filtrate 2, and obtaining a Chinese medicine composition decoction for treating herpes zoster neuralgia;

[0017] Step 3, concentrating the decoction into a clear paste, adding dextrin, stirring until the material becomes soft, granulating, drying, whole grains, and packaging to obtain the Chinese medicine composition granules for treating herpetic neuralgia.

[0018] Furthermore, in step three, the relative density of the clear paste is 1.30 at 30°C.

[0019] Furthermore, the added amount of the dextrin is 1.28 times that of the clear paste.

[0020] Furthermore, in step three, alcohol is added at the same time as dextrin, the mass fraction of the alcohol is 95%, and the amount of the alcohol added accounts for 2.5% of the total mass.

[0021] Furthermore, the drying temperature is 70°C-75°C, and the drying time is 1 hour.

[0022] In a third aspect, the present invention further discloses a use of the above-mentioned traditional Chinese medicine composition for treating herpes zoster neuralgia, which is used for treating herpes zoster neuralgia.

[0023] Beneficial effects of the present invention:

[0024] 1. The Chinese medicine composition for treating herpetic neuralgia of the present invention is composed of 14 Chinese medicines including stewed peach kernel, safflower, angelica, raw rehmannia root, chuanxiong, red peony root, Sichuan cyathula, platycodon, bupleurum, bran fried aurantium, vinegar corydalis, fried spiny jujube seed, Polygonum multiflorum, and liquorice. In the prescription, peach kernel can break blood stasis and relieve dryness, and safflower can promote blood circulation, remove blood stasis and relieve pain, and they are all monarch medicines. Red peony root and chuanxiong help the monarch to promote blood circulation and remove blood stasis, and cyathula enters the blood, is good at descending, can remove blood stasis, dredge blood vessels, make blood not stagnate in the chest, and phlegm and heat do not disturb, and they are all minister medicines. Raw rehmannia root nourishes yin and blood, and angelica nourishes blood, so that blood stasis is removed without hurting the body; red peony root clears heat and cools blood to clear blood stasis and heat. The three nourish blood and yin, clear heat and promote blood circulation, and are all adjuvant medicines. Platycodon and Fructus Aurantii Immaturus act one by one to ascend and the other by one to descend, which can relieve chest tightness and promote qi circulation. Platycodon can also carry medicine upward, while Bupleurum can soothe the liver and relieve depression, and ascend to the clear yang. Used together with Platycodon and Fructus Aurantii Immaturus, it is especially good at regulating qi and removing stagnation, so that qi and blood can flow. Corydalis yanhusuo promotes qi and relieves pain, while Polygonum multiflorum and Semen Ziziphi Spinosae nourish blood and soothe the mind. All of them are adjuvants, and the whole formula has the functions of promoting qi and blood circulation, removing stasis and relieving pain, and tranquilizing the mind. Clinical use in the treatment of herpes zoster neuralgia and animal efficacy experiments have shown that it has significant efficacy without adverse reactions, achieving an organic combination of macro-control and micro-targeting in the treatment of herpes zoster neuralgia.

[0025] 2. The Chinese medicine composition for treating herpetic neuralgia of the present invention can be prepared into a decoction of Chinese medicine composition for treating herpetic neuralgia or granules of Chinese medicine composition for treating herpetic neuralgia according to treatment needs. When used as a decoction, the decocting method is simple and the effect of warm administration is good; when used as granules, after strict preparation parameters, such as relative density of clear paste, amount of dextrin, amount of ethanol, etc., the granules can have good formability, and the process parameters in actual production are stable, reliable, reasonable and stable. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The present invention will be further described below in conjunction with the accompanying drawings.

[0027] Figure 1 This is a graph showing the results of the preliminary safety evaluation (HE staining) of the Chinese medicine composition granules for treating herpetic neuralgia of the present invention. DETAILED DESCRIPTION

[0028] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] The experimental methods in the following examples, unless otherwise specified, are all conventional methods, and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial channels.

[0030] Example 1

[0031] This embodiment discloses a traditional Chinese medicine composition for treating herpetic neuralgia, which is composed of the following components in parts by weight: 10g of stewed peach kernel, 10g of safflower, 10g of angelica, 10g of raw rehmannia, 10g of chuanxiong, 10g of red peony root, 10g of chuanxiong, 5g of platycodon, 10g of bupleurum, 5g of stir-fried fructus aurantii with bran, 15g of vinegar-corydalis, 15g of stir-fried spiny jujube kernel, 15g of Polygonum multiflorum, and 5g of liquorice; all of the above components are from Wuxi Traditional Chinese Medicine Hospital.

[0032] The above Chinese herbal components are decocted into an edible decoction (decocted by the Chinese Herbal Decoction Center of Wuxi Traditional Chinese Medicine Hospital), and the method is as follows: prepare the raw material components according to the proportion and mix them, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep it for 1 hour after boiling, filter to obtain filter material 1 and filtrate 1; add 8 times the amount of water to filter material 1, then heat and boil, keep it for 1 hour after boiling, filter to obtain filter material 2 and filtrate 2; combine filtrate 1 and filtrate 2, and bag them, 200 mL per bag.

[0033] Experimental Example 1

[0034] A randomized controlled trial was used to test the efficacy of the Chinese medicine composition for treating herpes zoster neuralgia disclosed in Example 1, and patients meeting the symptoms of herpes zoster neuralgia were selected for the experiment. The specific method was carried out in sequence according to the following process 1 to process 6.

[0035] 1. Determine the diagnostic criteria for herpes zoster neuralgia symptoms

[0036] 1. Western medicine diagnostic criteria

[0037] The diagnostic criteria for SHN and PHN were formulated with reference to the "Chinese expert consensus on short-term spinal cord stimulation for the treatment of herpetic-related neuralgia-A Chinese nationwide expert consensus": ① There is a clear history of herpes zoster. The rash has appeared for one month or more since the onset of herpes zoster, and there is still neuralgia or recurrent pain in the skin corresponding to the nerve distribution area; ② The nature of the pain can be burning, electric shock, knife-like, needle-like or tearing. One type of pain can be dominant, or multiple pains can coexist; ③ The degree of pain varies, and there is no definite relationship with the severity of the rash.

[0038] 2. TCM diagnostic criteria

[0039] According to the discussion of herpes zoster in the TCM Diagnosis and Treatment Guidelines for Herpes zoster (2014 Revised Edition), the diagnostic criteria for qi stagnation and blood stasis syndrome of TCM are proposed: ① Main symptoms: After the rash subsides, the local pain continues and is unbearable, radiating to the surrounding area. In severe cases, the pain can last for several months or more. ② Associated symptoms: chest and flank distension and discomfort, emotional anxiety; dark purple tongue or ecchymosis, white fur, and stringy pulse.

[0040] 3. Inclusion criteria

[0041] ① Meet the diagnostic criteria of TCM syndrome differentiation (Qi stagnation and blood stasis type); ② Meet the Western medicine diagnostic criteria for herpes zoster neuralgia, and the pain area is limited to the innervation range of T1 to T12 nerves on one side; ③ The patient age limit is 50 to 80 years old, including these two age groups; ④ The visual analogue scale (VAS) is ≥ 4 points; ⑤ No related drugs have been taken or applied externally within 3 days before treatment; ⑥ The patient or family member has given informed consent and can voluntarily sign the informed consent form.

[0042] 4. Exclusion criteria

[0043] ① Pregnant or lactating women; ② Those with severe local infections or other skin diseases that may interfere with diagnosis and treatment; ③ Those with neuralgia caused by other diseases or other influencing factors; ④ Those with primary diseases of the heart, brain, kidney, liver and other systems, malignant tumors, bleeding tendency, autoimmune diseases and mental illness; ⑤ Those with allergic constitution or allergies to the ingredients (traditional Chinese medicine, western medicine) to be used in this study; ⑥ Those with severe cognitive impairment and unable to complete the relevant questionnaire scores; ⑦ Those who find it difficult to make a correct evaluation of the effectiveness and safety of the treatment, and those who do not cooperate with the investigation and have poor compliance.

[0044] 5. Elimination and shedding standards

[0045] (1) Exclusion criteria: ① Those who have serious adverse events and should stop the trial; ② Those who are not suitable to continue participating in the trial due to other complications or special physiological changes during the study; ③ Those who have insufficient compliance or refuse to continue treatment; ④ Those who voluntarily request to withdraw from the clinical trial.

[0046] (2) Dropout criteria: patients who did not receive complete treatment and testing and were lost to follow-up.

[0047] 2. Selection of patients in the control group and the observation group

[0048] Based on the above diagnostic criteria for herpes zoster neuralgia symptoms, 60 patients who met the criteria and were treated in Wuxi Hospital of Traditional Chinese Medicine from March to August 2024 were selected and divided into a control group (n=30) and an observation group (n=30) using a random number table method.

[0049] 1. Control group: 11 males (36.67%) and 19 females (63.33%), aged 55 to 80 years old, with an average age of (71.60±7.87) years old; weight 30 to 85 kg, with an average weight of (60.20±12.04) kg; disease course 2 to 9 months, with an average disease course of (2.37±1.10) months.

[0050] 2. Observation group: 12 males (40.00%) and 18 females (60.00%); aged 50-80 years old, with an average age of (70.63±9.15) years old; weight 45-80 kg, with an average weight of (60.57±9.24) kg; disease course 2-7 months, with an average disease course of (2.53±1.43) months.

[0051] There was no significant difference in the general information of the two groups of patients (P>0.05), and they were comparable, as shown in Table 1 below:

[0052] Table 1 Comparison of general information of patients in the two groups

[0053]

[0054] 3. Determine the treatment plan for patients in the control group and observation group

[0055] 1. Control group

[0056] ① Basic Western medicine treatment: Gabapentin capsules (Zhejiang Yongtai Pharmaceutical Co., Ltd., approval number H20223321, 0.3g), 0.3g / time, taken in increasing frequency of 1 time / day, 2 times / day, and 3 times / day in the first 3 days to adapt to the drug. From the 4th day, the patient will maintain a dose of 0.3g 3 times a day for 4 consecutive weeks.

[0057] ②Ultrasound-guided thoracic paravertebral nerve block: Place the Siemens P300 low-frequency convex array ultrasound probe in parallel at a horizontal position 2.5 cm away from the target thoracic spinous process and perform a transverse axial scan to determine the position of the thoracic spinous process, transverse process, pleura and costotransverse ligament under ultrasound, and then use color Doppler mode to confirm that there are no vulnerable blood vessels in the puncture path. Then, under real-time ultrasound guidance, use a 10-cm-long No. 7 puncture needle and use the in-plane technique to penetrate the skin and accurately enter the intertransverse ligament until it reaches the paravertebral space. After confirming that there is no blood in the aspiration, inject 10 ml of compound anti-inflammatory analgesic solution. The liquid consists of the following ingredients: 7.8 ml of 0.9% sodium chloride injection (China Otsuka Pharmaceutical Co., Ltd., approval number H20043271), 1 ml of bupivacaine hydrochloride injection (Shanghai Zhaohui Pharmaceutical Co., Ltd., approval number H20056442), 0.2 ml of dexamethasone acetate injection (Chengdu Tiantaishan Pharmaceutical Co., Ltd., approval number H51020723) and 1 ml of vitamin B12 injection (Shijiazhuang Yinhu Pharmaceutical Co., Ltd., approval number H14022573). The correct injection is determined by observing the forward displacement of the pleura and the widening of the paravertebral space through ultrasound images, once a week, for 4 consecutive weeks.

[0058] 2. Observation Group

[0059] On the basis of the treatment plan of the control group, a Chinese medicine treatment plan was added. The specific Chinese medicine treatment plan was as follows: a decoction of the Chinese medicine composition for treating herpetic neuralgia of Example 1 was prepared daily for administration, and the patient took it warm after meals every morning and evening. One course of treatment was 2 weeks, and the treatment was continued for 4 weeks.

[0060] 4. Establishment of evaluation criteria for the treatment effects of the control group and the observation group

[0061] 1. Sleep quality

[0062] The Athens Insomnia Scale (AIS) scores of the two groups of patients were recorded before treatment, 2 weeks and 4 weeks after treatment to evaluate sleep quality. There are 8 scoring items in total, each with 4 levels. The cumulative scores of each item are statistically added to get the total score. A score of <4 points indicates no sleep disorder, a score of 4-6 points indicates sleep disorder, and a score of >6 points indicates insomnia.

[0063] 2. Serum Th1 / Th2 cytokine levels

[0064] Before treatment and 4 weeks after treatment, 5 ml of peripheral venous blood was collected from the patients. The blood samples were centrifuged at 3000 rpm for 10 minutes, and the separated supernatant was then stored in a low-temperature refrigerator at -80°C for subsequent use. The levels of Th1 cytokine interleukin-2 (IL-2) and Th2 cytokines interleukin-6 (IL-6) and interleukin-10 (IL-10) in the serum of the two groups of patients were detected by enzyme-linked immunosorbent assay (ELISA). The ELISA kits were purchased from Wuxi Weiwo Baisai Biotechnology Co., Ltd., with the catalog numbers EK0416, EK0397, and EK0410, respectively.

[0065] 3. Efficacy Index

[0066] The evaluation was formulated in accordance with the published “Guidelines for Clinical Research of New Chinese Medicines”

[10] , with the VAS score reduction rate (set with reference to the nimodipine method) as the basis for the evaluation results. The efficacy index = (VAS score before treatment - VAS score after treatment) / VAS score before treatment × 100%, which was divided into cure (skin pain completely or almost completely disappeared, and normal life was restored, efficacy index ≥ 95%), marked effect (skin pain was significantly reduced, and daily life conditions were significantly improved, 70% ≤ efficacy index < 95%), effective (skin pain was improved, and daily life conditions were slightly improved, 30% ≤ efficacy index < 70%), and ineffective (skin pain was not significantly reduced, or even aggravated, and daily life conditions did not improve or even worsened, efficacy index < 30%). The total effective rate = (number of clinically cured cases + number of markedly effective cases + number of effective cases) / total number of cases in this group × 100%.

[0067] 4. Adverse reaction rate

[0068] The possible adverse reactions that occurred during the treatment of the two groups were recorded. The incidence of adverse reactions = number of cases of adverse reactions / total number of cases in this group × 100%.

[0069] 5. Statistics and comparison of the treatment effects between the control group and the observation group

[0070] Based on the evaluation criteria of the treatment effect of the control group and the observation group, the collected case data were statistically analyzed using SPSS24.0 statistical software. The measurement data were presented in the form of mean ± standard deviation (±s). If the data obeyed the normal distribution and the variance was equal, the t test was used. If the data obeyed the normal distribution but the variance was unequal, the t' test was used. If it did not obey the normal distribution, the non-parametric test was used. The count data were expressed as n (%) and analyzed using the chi-square test. P value <0.05 was considered statistically significant.

[0071] 1. Comparison of VAS scores between the control group and the observation group

[0072] After 1, 2, 3 and 4 weeks of treatment, the VAS scores of the two groups of patients decreased compared with those before treatment, and the difference before and after treatment was statistically significant (P < 0.05). Before and 1 week after treatment, there was no statistically significant difference in VAS scores between the two groups (P > 0.05), but after 2, 3 and 4 weeks of treatment, the VAS scores of the observation group were lower than those of the control group, and the difference was statistically significant (P < 0.05), as shown in Table 2 below:

[0073] Table 2 Comparison of VAS scores between the two groups before and after treatment (points, )

[0074] Group n Before treatment 1 week of treatment 2 weeks of treatment 3 weeks of treatment 4 weeks of treatment Control group 30 6.50±1.78 5.47±1.74* 4.63±1.90* 3.50±2.10* 2.90±2.34* Observation Group 30 6.77±1.77 5.13±1.48* <![CDATA[3.50±1.33* # ]]> <![CDATA[2.27±1.39* # ]]> <![CDATA[1.40±1.35* # ]]>

[0075] Note: Compared with the same group before treatment, *P<0.05; compared with the control group at the same time point, # P<0.05

[0076] 2. AIS score results of the control group and the observation group

[0077] After 2 and 4 weeks of treatment, the AIS scores of the two groups of patients were lower than those before treatment, and the difference before and after treatment was statistically significant (P < 0.05). Before treatment, there was no statistically significant difference in AIS scores between the two groups (P > 0.05), but after 2 and 4 weeks of treatment, the AIS score of the observation group was lower than that of the control group, and the difference was statistically significant (P < 0.05), as shown in Table 3 below:

[0078] Table 3 Comparison of AIS scores between the two groups before and after treatment (points, )

[0079] Group n Before treatment 2 weeks of treatment 4 weeks of treatment Control group 30 13.27±5.88 8.53±3.99* 5.10±2.59* Observation Group 30 13.03±5.87 6.03±2.82*# 3.03±2.17*#

[0080] Note: Compared with the same group before treatment, *P<0.05; compared with the control group at the same time point, #P<0.05

[0081] 3. Comparison of Th1 / Th2 cytokine levels between the control group and the observation group

[0082] After 4 weeks of treatment, the IL-2 levels of the two groups of patients increased compared with those before treatment, while the IL-6 and IL-10 levels decreased, and the difference before and after the treatment was statistically significant (P < 0.05). Before treatment, there was no statistically significant difference in the levels of IL-2, IL-6, and IL-10 between the two groups (P > 0.05), but after 4 weeks of treatment, the IL-2 level in the observation group was higher than that in the control group, while the IL-6 and IL-10 levels were lower than those in the control group, and the difference was statistically significant (P < 0.05), as shown in Table 4 below:

[0083] Table 4 Comparison of serum Th1 / Th2 cytokine levels between the two groups before and after treatment (pg / ml, )

[0084]

[0085]

[0086] Note: Compared with the same group before treatment, *P<0.05; compared with the control group after treatment, #P<0.05

[0087] 4. Comparison of clinical efficacy between the control group and the observation group

[0088] After the treatment, the total effective rate of the control group was 73.33%, while that of the observation group was 93.33%. The efficacy of the observation group was better than that of the control group, and the difference was statistically significant (P < 0.05), as shown in Table 5 below:

[0089] Table 5 Comparison of clinical efficacy between the two groups of patients [cases (%)]

[0090] Group n get well Significant effect efficient invalid Total effective Control group 30 7(23.33) 6(20.00) 9(30.00) 8(26.67) 22(73.33) Observation Group 30 11(36.67) 12(40.00) 5(16.67) 2(6.67) 28(93.33)#

[0091] Note: Compared with the control group, #P<0.05

[0092] 5. Comparison of adverse reaction rates between the control group and the observation group

[0093] In the control group, one patient reported dizziness (3.33%), another reported chest tightness (3.33%), and one patient in the observation group had abdominal pain (3.33%). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05), as shown in Table 6 below:

[0094] Table 6 Comparison of the incidence of adverse reactions between the two groups of patients [cases (%)]

[0095] Group n Dizziness Chest tightness stomach ache Total occurrence Control group 30 1(3.33) 1(3.33) 0(0.00) 2(6.67) Observation Group 30 0(0.00) 0(0.00) 1(3.33) 1(3.33)#

[0096] Note: Compared with the control group, #P>0.05

[0097] 6. Analyze and summarize the comparison results between the control group and the observation group and draw conclusions

[0098] 1. By comparing the results, it can be observed that the VAS scores of the two groups of patients showed a downward trend after 1, 2, 3 and 4 weeks of treatment. Especially after the 2nd, 3rd and 4th week of treatment, the VAS scores of the observation group were significantly lower than those of the control group. This result shows that the Chinese medicine composition prescription for the treatment of herpes zoster neuralgia combined with paravertebral nerve block therapy has a positive effect on alleviating patients' neuropathic pain.

[0099] 2. Further analysis found that after the 2nd and 4th weeks of treatment, the AIS scores of both groups of patients decreased, and the decrease in the observation group was more obvious, indicating that the combined therapy can not only effectively relieve pain, but also significantly reduce insomnia, thereby improving the overall sleep quality of patients. Some studies have emphasized the connection between insomnia and pain tolerance, believing that in PHN patients, insomnia will reduce pain tolerance and increase sensitivity to pain, and that improved sleep quality is positively correlated with reduced pain intensity, which is consistent with the results of this experiment.

[0100] 3. The results of this experiment showed that after 4 weeks of treatment, the serum IL-2 levels of both groups of patients increased, while the IL-6 and IL-10 levels decreased. These changes in the observation group were more significant than those in the control group, indicating that the Zhuyu Tongluo prescription can regulate the level of immune cytokines in the body, correct the Th1 / Th2 imbalance, reduce inflammatory response, improve the body's immune function, and promote disease recovery.

[0101] 4. In this experiment, 1 case of dizziness and 1 case of chest tightness occurred in the control group, and 1 case of abdominal pain occurred in the observation group. The symptoms of the three patients were relieved without any special treatment. Blood pressure, electrocardiogram, blood routine, liver and kidney function examinations were performed, and no abnormalities were found. The treatment methods of both groups were safe and reliable, and the total effective rate of the group treated with Zhuyu Tongluo prescription was significantly higher than that of the group treated with western medicine alone.

[0102] In summary, this experiment confirms that the Chinese medicine composition for treating herpetic neuralgia in Example 1 of the present invention is effective in relieving pain in patients with qi stagnation and blood stasis type, and can not only effectively improve the sleep quality of patients, but also enhance the body's immune function, thereby having a positive impact on the treatment of SHN and PHN patients.

[0103] In order to further demonstrate the effect of the Chinese medicine composition for treating herpetic neuralgia of the present invention in relieving pain in patients with qi stagnation and blood stasis, the following examples are set up on the basis of Example 1, and the effect test is carried out on each group of examples.

[0104] Example 2

[0105] This embodiment discloses a traditional Chinese medicine composition for treating herpetic neuralgia, which is composed of the following components in parts by weight: 20g of stewed peach kernel, 20g of safflower, 20g of angelica, 20g of raw rehmannia, 9g of chuanxiong, 20g of red peony root, 20g of chuanxiong, 9g of platycodon, 9g of bupleurum, 9g of stir-fried fructus aurantii with bran, 30g of vinegar corydalis, 30g of stir-fried spiny jujube kernel, 20g of radix polygoni multiflori, and 10g of licorice; all of the above components are from Wuxi Traditional Chinese Medicine Hospital.

[0106] The above Chinese medicine components are decocted into an edible decoction (decocted by the Chinese Medicine Decoction Center of Wuxi Traditional Chinese Medicine Hospital), and the method is the same as that of Example 1.

[0107] The prescription of this embodiment is used to treat the patient, as follows:

[0108] Patient Wu XX, female, 80 years old, hospital number: 202317776, first visit date: 2023.06.07;

[0109] Chief complaint: rash on the left side of the chest and back accompanied by pain and discomfort for 40 days;

[0110] Current medical history: The patient had pain in the left chest and back without obvious cause 40 days ago, and the rash showed a large number of erythema, herpes, redness, swelling and congestion. He went to an external hospital for treatment. After treatment of nerve nutrition and analgesia, the patient's left chest and back skin was basically scabbed, the scab had fallen off, and local dark red pigmentation was present. The pain was manifested as continuous acupuncture pain and distension, with occasional explosive pain, pain score of 7, and awakening from pain at night. Now: The patient is conscious and mentally sound, with pain in the left chest and back, which is like acupuncture, and sometimes nausea and vomiting, without aversion to cold or fever, without coughing or sputum, without obvious weight loss, no abdominal pain or diarrhea, poor sleep, normal urination, and constipation. The patient is conscious and mentally sound, with a painful face, moderate body shape, clear language, and no abnormal odor. The tongue is dark red, the fur is thin and white, and the pulse is stringy and thin.

[0111] Past history: history of hypertension for 20 years, the highest ever reaching 180 / 100 mmHg, usually treated with oral amlodipine besylate tablets 2.5 mg QD, valsartan capsules 80 mg QD, and metoprolol succinate sustained-release tablets 23.75 mg QD; had coronary heart disease for 10 years, usually treated with oral clopidogrel bisulfate tablets 75 mg QD, and atorvastatin calcium tablets 10 mg QN; had hypothyroidism for 8 years, usually treated with oral levothyroxine sodium 25 ug QD.

[0112] TCM diagnosis: Herpes zoster (a typical case of qi stagnation and blood stasis);

[0113] Western medicine diagnosis: 1. Herpes zoster neuralgia 2. Hypertension stage 3 (extremely high risk) 3. Coronary atherosclerotic heart disease 4. Hypothyroidism.

[0114] Treatment plan: The prescription of this embodiment is 1 dose (2 bags) per day, taken warm twice a day in the morning and evening, 7 doses are decocted.

[0115] At discharge: the patient's pain was significantly relieved, sleep at night was significantly improved, and the VAS score changed from 7 to 3.

[0116] Example 3

[0117] This embodiment discloses a traditional Chinese medicine composition for treating herpetic neuralgia, which is composed of the following components in parts by weight: 10g of stewed peach kernel, 10g of safflower, 10g of angelica, 10g of raw rehmannia, 10g of chuanxiong, 10g of red peony root, 10g of chuanxiong, 5g of platycodon, 10g of bupleurum, 5g of stir-fried fructus aurantii with bran, 15g of vinegar-corydalis, 15g of stir-fried spiny jujube kernel, 15g of Polygonum multiflorum, and 5g of liquorice; all of the above components are from Wuxi Traditional Chinese Medicine Hospital.

[0118] The above Chinese medicine components are decocted into an edible decoction (decocted by the Chinese Medicine Decoction Center of Wuxi Traditional Chinese Medicine Hospital), and the method is the same as that of Example 1.

[0119] The prescription of this embodiment is used to treat the patient, as follows:

[0120] Patient Tian XX, female, 60 years old, hospital number: 202325638, first visit date: 2023.08.08;

[0121] Chief complaint: pain in the right side of the chest and back for more than 2 months;

[0122] Current medical history: The patient had pain in the right side of the chest and back without obvious cause 2 months ago, and the rash showed a large number of erythema, herpes, redness, swelling and congestion. He then went to the dermatology department of our hospital for treatment. After antiviral, nerve nutrition, and analgesia treatment, the patient's right chest and back skin had scabs, the scabs had fallen off, and local dark red pigmentation, the pain was manifested as continuous needle-like and burning pain, with occasional explosive pain, pain score of 8, and awakening from pain at night. At present: The patient is conscious and mentally sound, with pain in the right side of the chest and back, like needles, nausea and vomiting, no aversion to cold, fever, no cough, sputum, no obvious weight loss, no abdominal pain and diarrhea, sometimes dizziness and discomfort, poor sleep, normal urination, and constipation. The tongue is dark red, the fur is thin and white, and the pulse is stringy and thin.

[0123] Past history: 15-year history of hypertension, the highest ever reaching 180 / 100 mmHg, usually treated with olmesartan hydrochlorothiazide tablets and carvedilol tablets orally; 10-year history of diabetes, usually treated with metformin extended-release tablets and saxagliptin orally, and epalrestat orally for the prevention and treatment of neuropathy; 3-year history of lacunar infarction, currently feels dizzy and uncomfortable from time to time.

[0124] TCM diagnosis: Herpes zoster (a typical case of qi stagnation and blood stasis);

[0125] Western medicine diagnosis: 1. Herpes zoster neuralgia 2. Hypertension stage 3 (extremely high risk) 3. Type 2 diabetes 4. Personal history of cerebral infarction.

[0126] Treatment plan: The prescription of this embodiment is 1 dose (2 bags) per day, taken warm twice a day in the morning and evening, 7 doses are decocted.

[0127] At discharge: the patient's pain was significantly relieved, sleep at night was significantly improved, and the VAS score changed from 8 to 2.

[0128] Example 4

[0129] This embodiment discloses a traditional Chinese medicine composition for treating herpetic neuralgia, which is composed of the following components in parts by weight: 15g of stewed peach kernel, 15g of safflower, 20g of angelica, 20g of raw rehmannia, 10g of chuanxiong, 10g of red peony root, 10g of chuanxiong, 5g of platycodon, 9g of bupleurum, 5g of stir-fried aurantium with bran, 30g of vinegar-corydalis, 30g of stir-fried jujube kernel, 30g of Polygonum multiflorum, and 5g of liquorice; all of the above components are from Wuxi Traditional Chinese Medicine Hospital.

[0130] The above Chinese medicine components are decocted into an edible decoction (decocted by the Chinese Medicine Decoction Center of Wuxi Traditional Chinese Medicine Hospital), and the method is the same as that of Example 1.

[0131] The prescription of this embodiment is used to treat the patient, as follows:

[0132] Patient Jiang XX, female, 85 years old, hospital number: 202401353, first visit date: 2024.01.10;

[0133] Chief complaint: rash and pain on the left side of the neck and shoulder for more than 1 month;

[0134] Current medical history: The patient had pain in the left neck and shoulder without obvious cause one month ago, and the rash showed a large number of erythema, herpes, redness, swelling and congestion. He then went to the dermatology department of an external hospital for treatment. After antiviral, nerve nutrition, and analgesic treatment, the patient's left neck and shoulder skin was basically scabbed, the scab partially fell off, and there were local patches of dark red pigmentation. The pain was intermittent needle-like and burning pain, with occasional explosive pain, pain score 9, and awakening from pain at night. Now: The patient is conscious and mentally sound, with pain in the left neck and shoulder, which is needle-like, and sometimes nausea and vomiting, without chills, fever, cough, sputum, no obvious weight loss, no abdominal pain and diarrhea, poor sleep, normal urination, and constipation. The tongue is dark red, the fur is thin and white, and the pulse is stringy and thin.

[0135] Past medical history: He had a history of hypertension for more than ten years, with the highest blood pressure reaching 180 / 100 mmHg, and usually took oral irbesartan tablets for treatment.

[0136] TCM diagnosis: Herpes zoster (a typical case of qi stagnation and blood stasis);

[0137] Western medicine diagnosis: 1. Herpes zoster neuralgia 2. Hypertension stage 3 (extremely high risk).

[0138] Treatment plan: The prescription of this embodiment is 1 dose (2 bags) per day, taken warm twice a day in the morning and evening, 7 doses are decocted.

[0139] At discharge: the patient's pain was significantly relieved, sleep at night was significantly improved, and the VAS score changed from 9 to 4.

[0140] Example 5

[0141] This embodiment discloses a traditional Chinese medicine composition for treating herpetic neuralgia, which is composed of the following components in parts by weight: 15g of stewed peach kernel, 15g of safflower, 20g of angelica, 20g of raw rehmannia, 10g of chuanxiong, 10g of red peony root, 10g of chuanxiong, 5g of platycodon, 9g of bupleurum, 5g of stir-fried aurantium with bran, 30g of vinegar-corydalis, 30g of stir-fried jujube kernel, 30g of Polygonum multiflorum, and 5g of liquorice; all of the above components are from Wuxi Traditional Chinese Medicine Hospital.

[0142] The above Chinese medicine components are decocted into an edible decoction (decocted by the Chinese Medicine Decoction Center of Wuxi Traditional Chinese Medicine Hospital), and the method is the same as that of Example 1.

[0143] The prescription of this embodiment is used to treat the patient, as follows:

[0144] Patient Wang XX, female, 89 years old, hospital number: 202426989, first visit date: 2024.07.30;

[0145] Chief complaint: rash and pain on the right side of waist and abdomen for more than 4 months;

[0146] Current medical history: The patient had pain in the right waist and abdomen without obvious cause 4 months ago, and the rash showed a large number of erythema, herpes, redness, swelling and congestion. Then he went to the dermatology department of our hospital for treatment. After antiviral, nerve nutrition, analgesia and other treatments, the patient's right waist and abdomen skin was basically scabbed, the scab had fallen off, and local dark red pigmentation. Later, he was hospitalized in our department for paravertebral nerve block treatment, radiofrequency or microwave ablation (right T10-12), and epidural catheter injection treatment. The pain improved and he was discharged from the hospital. Recently, the subjective symptoms have worsened, and the pain score is 8. Now: The patient is conscious and mentally sound, with pain in the right waist and abdomen, which is needle-like, and there is nausea and vomiting from time to time, no chills, fever, no cough, sputum, no obvious weight loss, no abdominal pain and diarrhea, poor sleep, normal urination, and constipation. The patient is conscious and mentally sound, with a painful face, moderate body shape, clear language, and no abnormal odor. The tongue is dark red, the fur is thin and white, and the pulse is stringy and thin.

[0147] Past history: history of "hypertension" for many years, the highest reaching 160 / 100 mmHg, usually treated with oral felodipine sustained-release tablets and valsartan; history of dizziness, treated with oral betahistine; history of osteoporosis, treated with oral alfacalcidol and risedronate.

[0148] TCM diagnosis: Herpes zoster (typical case of qi stagnation and blood stasis)

[0149] Western medicine diagnosis: 1. Herpes zoster neuralgia 2. Hypertension stage 2 (high risk) 3. Osteoporosis.

[0150] Treatment plan: The prescription of this embodiment is 1 dose (2 bags) per day, taken warm twice a day in the morning and evening, 7 doses are decocted.

[0151] At discharge: the patient's pain was significantly relieved, sleep at night was significantly improved, and the VAS score changed from 8 to 3.

[0152] From the summary of Examples 2-5, it can be known that the Chinese medicine composition for treating herpes zoster neuralgia of Examples 2-5 has a good therapeutic effect on patients with herpes zoster neuralgia. Combined with the test results of the Chinese medicine composition for treating herpes zoster neuralgia of Example 1, it can be further explained that the Chinese medicine composition for treating herpes zoster neuralgia of the present invention is effective in relieving pain in patients with qi stagnation and blood stasis type.

[0153] Example 6

[0154] This embodiment discloses a method for preparing a decoction of a Chinese medicine composition for treating herpetic neuralgia based on Embodiments 1-5. The Chinese medicine compositions for treating herpetic neuralgia in Embodiments 1-5 are all decocted by the preparation method, and the specific steps are as follows:

[0155] Step 1: prepare and mix the raw material components according to the proportion, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep for 1 hour after boiling, and filter to obtain filter material 1 and filtrate 1;

[0156] Step 2: Add 8 times the amount of water to filter material 1, then heat and boil, keep boiling for 1 hour, filter to obtain filter material 2 and filtrate 2, and combine filtrate 1 and filtrate 2.

[0157] Experimental Example 2

[0158] The preparation effect test of the preparation method of the Chinese medicine composition decoction for treating herpetic neuralgia disclosed in Example 6 was carried out, and the specific method was carried out in sequence according to the following process 1 to process 5.

[0159] 1. Select experimental instruments and test drugs

[0160] 1. Instrument

[0161] (1) Agilent 1200 high performance liquid chromatograph (Agilent, USA);

[0162] (2) DAD diode array detector (Agilent, USA);

[0163] (3) BSA224S-CW electronic balance (Sartorius, Germany);

[0164] (4) KQ-300E ultrasonic cleaning machine (Kunshan Ultrasonic Instrument Co., Ltd.);

[0165] (5) RE52CS rotary evaporator (Shanghai Yarong Biochemical Instrument Factory).

[0166] 2. Drug testing

[0167] (1) Hydroxysafflor yellow A reference substance (batch number: 111637-202412, purity: 97.7%), purchased from China Food and Drug Administration;

[0168] (2) Paeoniflorin reference substance (batch number: 110736-202447, purity: 98.1%), purchased from China Food and Drug Inspection Institutes;

[0169] (3) The acetonitrile used in the HPLC was of chromatographic grade, the water was of ultrapure water, and the other reagents were of analytical grade.

[0170] 2. Establishment of the determination method of hydroxysafflor yellow A and paeoniflorin

[0171] (1) Chromatographic conditions

[0172] Chromatographic column: XBridge C18 (250 mm × 4.6 mm, 5 μm);

[0173] Column temperature: 30℃; Mobile phase:

[0174] Acetonitrile (A)-0.1% phosphoric acid water (B), gradient elution (0-7 min, 10%-15% A; 7-12 min, 15%-23% A; 12-17 min, 23%-27% A; 17-35 min, 27%-29%);

[0175] Detection wavelength: 230, 350 nm; flow rate: 1.0 mL·min-1; injection volume: 10 μL.

[0176] (2) Solution preparation

[0177] A. Preparation of reference solution: Accurately weigh appropriate amounts of hydroxysafflor yellow A and paeoniflorin reference substances, place them in volumetric flasks, and add 80% methanol to prepare mixed reference solutions with concentrations of 120 and 610 μg·mL-1, respectively.

[0178] B. Preparation of test solution: Accurately pipette 2 mL of the extract into a 10 mL volumetric flask, add 80% methanol to dilute to the scale, ultrasonicate (100 W, 40 kHz) for 10 min, shake well, filter, and take the filtrate as the test solution.

[0179] C. Preparation of negative sample solution: According to the Chinese medicine combination prescription for treating herpetic neuralgia of the present invention and the preparation method disclosed in Example 6, weigh the whole prescription pieces lacking safflower and lacking red peony root respectively for preparation, and then prepare according to the preparation method of the test solution to obtain the negative sample solution lacking safflower and the negative sample solution lacking red peony root.

[0180] (3) Linear relationship investigation

[0181] Accurately pipette 0.25, 0.50, 1.0, and 3.0 mL of the mixed reference solution respectively, dilute to 5 mL volumetric flask with methanol, inject according to the conditions under the "Chromatographic Conditions" item, and record the peak area. Draw a standard curve with the reference concentration (X, μg·mL-1) as the abscissa and the peak area (Y) as the ordinate. The results show that the concentrations of hydroxysafflor yellow A and paeoniflorin reference substances show good linear relationships in the range of 6-36 μg·mL-1 and 30.5-183 μg·mL-1, respectively, as shown in Table 7 below:

[0182] Table 7 Linear relationship investigation results

[0183]

[0184] (4) Determination of hydroxysafflor yellow A and paeoniflorin in safflower and red peony root slices

[0185] The samples were determined according to the methods under the [Content Determination] items of Carthamus tinctorius and Paeonia lactiflora in Part I of the 2020 edition of the Chinese Pharmacopoeia. Accurately weigh 0.4 g of safflower powder (passed through a No. 3 sieve) and prepare the test solution in accordance with the law. The results were calculated based on the dry product, and the content of hydroxysafflor yellow A (C27H32O16) in the safflower slices was 2.65%, which was in line with the provisions of the decoction pieces under the item of Carthamus tinctorius (Part I of the 2020 edition of the Chinese Pharmacopoeia); accurately weigh 0.5 g of Paeonia lactiflora crude powder, and prepare the test solution in accordance with the law. The results were calculated based on the dry product, and the content of paeoniflorin (C23H28O11) in the Paeonia lactiflora slices was 4.06%, which was in line with the provisions of the decoction pieces under the item of Paeonia lactiflora (Part I of the 2020 edition of the Chinese Pharmacopoeia).

[0186] 3. Orthogonal test of preparation method

[0187] (1) Orthogonal experimental design

[0188] The whole prescription medicinal materials were weighed according to the following prescription amount: 5g of stewed peach kernel, 5g of safflower, 5g of angelica, 5g of raw rehmannia root, 5g of chuanxiong, 5g of red peony root, 5g of Sichuan cyathula, 2.5g of platycodon, 5g of bupleurum, 2.5g of fried aurantium with bran, 7.5g of vinegar corydalis, 7.5g of fried spiny jujube kernel, 7.5g of Polygonum multiflorum, and 2.5g of liquorice, a total of 70g, 9 portions were taken for each, and soaked for 30 minutes. Orthogonal design experiment L9 (34) was adopted, and three factor levels A (decoction time), B (decoction times), and C (water addition amount) were selected. The orthogonal test scheme shown in Table 8 below was carried out according to the preparation method disclosed in Example 6, and the water was decocted and filtered, and the filtrate was combined and concentrated to 200mL to obtain 9 sample solutions of orthogonal test.

[0189] Table 8 Sample solution factors A, B, and C of 9 orthogonal tests

[0190]

[0191] (2) Determination of extract yield

[0192] Pipette 50 mL of each of the 9 samples into an evaporating dish of constant weight, and heat in a water bath until nearly dry. Dry in an oven at 105°C for 5 hours, cool for 30 minutes, and weigh. Dry for another 2 hours, cool, and weigh until constant weight. The extract yields of samples 1 to 9 are 21.80%, 29.76%, 35.25%, 24.85%, 33.82%, 35.71%, 28.22%, 32.97%, and 36.72%, respectively.

[0193] (3) Determination of the content and transfer rate of hydroxysafflor yellow A and paeoniflorin in samples

[0194] Accurately draw 2mL of the concentrated sample solution, place it in a 10mL volumetric flask, add 80% methanol to dilute to the scale, ultrasonicate for 10min, shake well, filter, and take the filtrate as the test solution. Inject according to the conditions under the "Chromatographic Conditions", record the peak area, and calculate the content of hydroxysafflor yellow A and paeoniflorin in the sample. Then calculate the transfer rate (%) of hydroxysafflor yellow A and paeoniflorin in the extract according to the following formula: transfer rate of hydroxysafflor yellow A (%) = content of hydroxysafflor yellow A in the decoction / content of hydroxysafflor yellow A in safflower × 100%; transfer rate of paeoniflorin (%) = content of paeoniflorin in the decoction / content of paeoniflorin in red peony × 100%.

[0195] The results of the orthogonal test of hydroxysafflor yellow A content and transfer rate are shown in Table 9 below:

[0196] Table 9 Orthogonal test results of hydroxysafflor yellow A content and transfer rate

[0197]

[0198]

[0199] The results of the orthogonal test of paeoniflorin content and transfer rate are shown in Table 10 below:

[0200] Table 10 Results of orthogonal test of paeoniflorin content and transfer rate

[0201]

[0202] 4. Analysis of orthogonal test results

[0203] The three factors of decoction time (A), decoction times (B), and water addition (C) were selected. The D factor was a blank item, which was used as an error item to estimate the experimental error in the orthogonal test calculation. Based on the fact that hydroxysafflor yellow A and paeoniflorin are the main active ingredients of safflower and red peony respectively, and the detection methods are mature, with good separation and strong specificity, the weights of forsythin and berberine are 40% respectively; taking into full consideration that this prescription is a compound Chinese medicine preparation for clinical use, its pharmacodynamic material basis is the joint action of multiple components, reflecting the evaluation of other compatible medicinal materials in the prescription, and the weight of extract yield is 20%. The orthogonal test optimization was carried out using comprehensive scoring indicators to ensure the reliability and rationality of the extraction process research. The extract yield, hydroxysafflor yellow A and paeoniflorin transfer rate were taken as the inspection indicators, and each indicator was scored comprehensively according to the proportion of 20%, 40%, and 40%, respectively. The total score was used as the optimization indicator for intuitive analysis and variance analysis.

[0204] The orthogonal test design and results are shown in Table 11 below:

[0205] Table 11 Orthogonal experimental design and results

[0206]

[0207]

[0208] Note: Comprehensive score = (sample extract yield / maximum extract yield in the sample) × 0.2 + (sample hydroxysafflor yellow A transfer rate / maximum hydroxysafflor yellow A transfer rate in the sample) × 0.4 + (sample paeoniflorin transfer rate / maximum paeoniflorin transfer rate in the sample) × 0.4

[0209] The variance analysis table between factors is shown in Table 12 below:

[0210] Table 12 Results of variance analysis among factors

[0211]

[0212] Note: F0.05(2,2)=19, F0.01(2,2)=99

[0213] According to the range R analysis in Table 11, the influencing factors are as follows: number of decoctions > amount of water added > decoction time. According to the K value, A3 = A2 > A1, B3 > B2 > B1, C1 > C3 > C2, and the optimal extraction process is A2B3C1, that is, add 8 times the amount of water, extract three times, each time for 1 hour. Through variance analysis, the results show that decoction time, number of decoctions, and amount of water added have no significant effect on the experiment. Combined with economic benefits and actual production and preparation conditions, the optimal extraction process is finally determined to be adding 8 times the amount of water, soaking for 30 minutes, keeping it for 1 hour after boiling, filtering it while hot, adding 8 times the amount of water to the residue, keeping it for 1 hour after boiling, filtering, and combining the extracts, which is the best extraction process.

[0214] 5. Verification test of preparation method

[0215] Weigh 5g of stewed peach kernel, 5g of safflower, 5g of angelica, 5g of raw rehmannia, 5g of chuanxiong, 5g of red peony root, 5g of Sichuan cyathula, 2.5g of platycodon, 5g of bupleurum, 2.5g of fried aurantium with bran, 7.5g of vinegar corydalis, 7.5g of fried spiny jujube kernel, 7.5g of radix polygoni multiflori, 2.5g of licorice, add 8 times of water, soak for 30min, keep for 1h after boiling, and filter while hot. Add 8 times of water to the residue, keep for 1h after boiling, filter with gauze while hot, combine the extracts, and concentrate to 200mL. Determine the extract yield, hydroxysafflor yellow A and paeoniflorin transfer rate, respectively, and the results are shown in Table 13 below:

[0216] Table 13 Extract yield, hydroxysafflor yellow A and paeoniflorin transfer rate results

[0217]

[0218] By analyzing the data in Table 13, it can be found that the obtained result is close to the maximum value of the orthogonal result. Therefore, it can be judged that the preparation method of the Chinese medicine composition decoction for treating herpetic neuralgia in Example 6 is feasible and stable.

[0219] Example 7

[0220] This example discloses a method for preparing a Chinese medicine composition granule for treating herpetic neuralgia based on Example 6, and the specific steps are as follows:

[0221] Step 1: prepare and mix the raw material components according to the proportion, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep for 1 hour after boiling, and filter to obtain filter material 1 and filtrate 1;

[0222] Step 2, add 8 times the amount of water to filter material 1, then heat and boil, keep boiling for 1 hour, filter to obtain filter material 2 and filtrate 2, combine filtrate 1 and filtrate 2 to obtain a combined liquid;

[0223] Step 3. Concentrate the combined liquid to a clear paste with a relative density of 1.30 at 30°C, add dextrin and 95% ethanol by mass, the ratio of dextrin to the clear paste is 1:1.28, and the amount of ethanol is 2.5% of the total mass; according to the standard of "holding into a ball and falling apart when pressed lightly", the mixed auxiliary materials are made into a soft material, and the prepared soft material is prepared into granules by extrusion using a 14-mesh sieve, and the prepared granules are placed at 70-75°C for drying. After drying for 1 hour, use a 16-mesh sieve to sieve and package again.

[0224] The preparation effect test of the preparation method of the Chinese medicine composition granules for treating herpetic neuralgia disclosed in Example 7 was carried out, and the specific method was carried out in sequence according to the following process 1 to process 6.

[0225] 1. Single density test (30℃)

[0226] The Chinese medicine composition granules for treating herpetic neuralgia were prepared according to the preparation method of Example 7, except that when selecting the relative density of the clear paste, the relative density of the clear paste was concentrated to 1.10, 1.15, 1.20, 1.25, and 1.30, respectively, the ratio of the drug-excipient (dextrin) ratio was set to 1:1.5, 95% ethanol was used as a wetting agent for investigation, and granulation was performed after uniform mixing. The molding rate of the obtained Chinese medicine composition granules for treating herpetic neuralgia was tested, and the test results are shown in Table 14 below:

[0227] Table 14 Single density test results

[0228]

[0229] By analyzing the data in Table 14, it can be learned that when the relative density of the clear paste is 1.30, the forming rate of the particles of the traditional Chinese medicine composition for treating herpetic neuralgia is the best, so 1.30 is the optimal relative density of the clear paste.

[0230] 2. Test on the dosage ratio of single dextrin and clear paste

[0231] The Chinese medicine composition granules for treating herpetic neuralgia were prepared according to the preparation method of Example 7, except that when selecting the dosage ratio of dextrin to clear paste, the dosage ratio of dextrin to clear paste was set to 1:1, 1:1.25, 1:1.5, 1:1.75, and 1:2, respectively, the relative density of the clear paste was concentrated to an optimal 1.30 (30° C.), 95% ethanol was used as a wetting agent for investigation, and granulation was performed after uniform mixing. The molding rate of the obtained Chinese medicine composition granules for treating herpetic neuralgia was tested, and the test results are shown in Table 15 below:

[0232] Table 15 Test results of the dosage ratio of single dextrin and clear paste

[0233]

[0234] By analyzing the data in Table 15, it can be found that when the dosage ratio of dextrin to clear paste is 1:1.25, the molding rate of the particles of the traditional Chinese medicine composition for treating herpetic neuralgia is the best, so 1:1.25 is the optimal ratio of clear paste to dextrin.

[0235] 3. Single ethanol dosage test

[0236] The Chinese medicine composition granules for treating herpetic neuralgia were prepared according to the preparation method of Example 7, except that when selecting the proportion of ethanol dosage, 95% ethanol was used as a wetting agent for investigation, and the dosage was 0, 1%, 2%, and 3% of the total mass. The relative density of the clear paste was concentrated to 1.30 (30° C.), and the dextrin ratio was set to 1:1.5. After mixing evenly, granulation was performed, and the molding rate of the obtained Chinese medicine composition granules for treating herpetic neuralgia was tested. The test results are shown in Table 16 below:

[0237] Table 16 Single ethanol addition test results

[0238]

[0239] By analyzing the data in Table 15, it can be learned that when the amount of ethanol added accounts for 3% of the total mass, the molding rate of the particles of the traditional Chinese medicine composition for treating herpetic neuralgia is the best, so 1:1.25 is the optimal ratio of clear paste to dextrin.

[0240] 4. Orthogonal test

[0241] 1. Set up orthogonal test items and methods

[0242] (1) Formation rate: Take a certain amount of granules, collect the particles that can pass through the No. 1 sieve but not through the No. 5 sieve, and calculate according to the formula: Formation rate (%) = m0 / m×100; where: m0 is the mass of particles that pass through the No. 1 sieve but not through the No. 5 sieve; m is the total mass of the weighed particles.

[0243] (2) Hausner ratio (HR): Take a certain amount of granules and put them into a dry measuring cylinder. Record the apparent volume V0 and tap to determine the compacted volume VF. Calculate the Hausner ratio and take the average of three replicates. Hausner ratio = V0 / VF.

[0244] (3) Determination of the angle of repose: The fixed funnel method was used to determine the angle of repose. The angle of repose of different excipients in the granules was calculated according to the formula and the average value was taken after three parallel tests; α(°) = arctan(H / R); where H is the height of the bottom of the funnel from the coordinate paper, and R is the radius of the bottom of the cone measured by the coordinate paper.

[0245] (4) Determination of moisture absorption rate: Weigh the constant weight granules accurately, transfer them into a constant weight weighing bottle, open the lid, and place them in a NaCl supersaturated desiccator for 48 hours; moisture absorption rate (%) = (mass of granules after moisture absorption - mass of granules before moisture absorption) / mass of granules before moisture absorption × 100.

[0246] (5) Dissolution time: Weigh 5 g of qualified granules and place them in 100 mL of hot water (100°C). Stir with a glass rod and observe immediately. All soluble granules should be dissolved. Calculate the dissolution time and take the average of three replicates.

[0247] 2. Orthogonal Experimental Design

[0248] Select three factor levels A (relative density of clear paste), B (ratio of dextrin to clear paste), and C (amount of ethanol), and prepare Chinese medicine composition granules for treating herpetic neuralgia according to the preparation method disclosed in Example 7 (the only difference is that the factor levels A, B, and C are changed accordingly), and 9 granule samples of orthogonal test are obtained, as shown in Table 17 below:

[0249] Table 17 Factors A, B, and C of 9 orthogonal test granule samples

[0250]

[0251]

[0252] Then, the molding rate, angle of repose, bulk density and moisture absorption rate of the 9 groups of granule samples were determined according to the orthogonal test test items and methods. Finally, the score of each sample was calculated, and intuitive analysis and variance analysis were performed.

[0253] The orthogonal test design and results are shown in Table 18 below:

[0254] Table 18 Orthogonal experimental design and results

[0255]

[0256] Note: Comprehensive score = 40% × forming rate + 20% × moisture absorption rate + 20% × dissolution time + 10% × angle of repose + 10% × Hausner ratio.

[0257] The variance analysis table between factors is shown in Table 19 below:

[0258] Table 19 Results of variance analysis between factors

[0259]

[0260] Note: F0.05(2,2)=19, F0.01(2,2)=99

[0261] According to the range R analysis in Table 18, the influencing factors are as follows: ethanol dosage > dextrin to clear paste dosage ratio > relative density of clear paste. According to the K value, A2>A1>A3, B3>B2>B1, C1>C2>C3. The preliminary molding process is A2B3C1, that is, the filtrate is concentrated into a clear paste with a relative density of 1.30 (30°C). Add 1.28 times the amount of dextrin, use 95% alcohol as a wetting agent, and add 2.5% of the total mass.

[0262] According to Table 19, the variance analysis shows that the density of the liquid medicine, the ratio of dextrin to the clear paste, and the amount of ethanol have no significant effect on the experiment. The molding process is preliminarily determined to be the relative density of the clear paste is 1.30 (30°C), 1.28 times the amount of dextrin is added, 95% alcohol is used as a wetting agent, 2.5% of the total mass is added, stirred into a soft material, granulated, the particles are dried at 70-75°C for 1h, granulated, and packaged, that is, the important composition particle preparation method disclosed in Example 7 is the best preparation method.

[0263] The optimal amount of ethanol was selected according to the molding rate after granulation.

[0264] 5. Verification test of preparation method

[0265] 1. Forming effect verification

[0266] Weigh 5g of stewed peach kernel, 5g of safflower, 5g of angelica, 5g of raw rehmannia, 5g of chuanxiong, 5g of red peony root, 5g of chuanxiong, 2.5g of platycodon, 5g of bupleurum, 2.5g of fried aurantium with bran, 7.5g of vinegar corydalis, 7.5g of fried spiny jujube kernel, 7.5g of radix polygoni multiflori, and 2.5g of liquorice; weigh three portions in total. Add 8 times the amount of water, soak for 30min, keep for 1h after boiling, filter while hot, add 8 times the amount of water to the residue, keep for 1h after boiling, filter, combine the extracts, concentrate the clear paste to a relative density of 1.30 (30℃), add 1.28 times the amount of dextrin, use 95% alcohol as a wetting agent, add 2.5% of the total mass, stir to make a soft material, granulate, dry the granules at 70-75℃, granulate, and package. The results of the investigation are shown in Table 20 below:

[0267] Table 20 Investigation results of molding effect verification

[0268]

[0269] By analyzing the data in Table 20, it can be seen that under the preparation method of Example 7, the prepared Chinese medicine composition particles for treating herpetic neuralgia have good formability.

[0270] Example 8

[0271] Example 7

[0272] This embodiment discloses a method for preparing a Chinese medicine composition granule for treating herpes zoster neuralgia, and the specific steps are as follows:

[0273] Step 1: prepare and mix the raw material components according to the proportion, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep for 1 hour after boiling, and filter to obtain filter material 1 and filtrate 1;

[0274] Step 2, add 8 times the amount of water to filter material 1, then heat and boil, keep boiling for 1 hour, filter to obtain filter material 2 and filtrate 2, combine filtrate 1 and filtrate 2 to obtain a combined liquid;

[0275] Step 3. Concentrate the combined liquid to a clear paste with a relative density of 1.30 at 30°C, and the usage ratio of dextrin to clear paste is 1:1.28; make the mixed auxiliary materials into a soft material according to the standard of "forming a ball by hand and falling apart by light pressure", and prepare the prepared soft material into granules by extrusion using a 14-mesh sieve, and place the prepared granules at 70-75°C for drying. After drying for 1 hour, use a 16-mesh sieve again to sieve and package.

[0276] The preparation method of the Chinese medicine composition granules for treating herpetic neuralgia in Example 8 was pilot tested, as follows:

[0277] Feed amount for pilot test: 6kg of stewed peach kernel, 6kg of safflower, 6kg of angelica, 6kg of raw rehmannia, 6kg of chuanxiong, 6kg of red peony root, 6kg of chuanxiong, 3kg of platycodon, 6kg of bupleurum, 3kg of fried aurantium with bran, 9kg of vinegar corydalis, 9kg of fried spiny jujube kernel, 9kg of Polygonum multiflorum, and 3kg of licorice; three portions in total.

[0278] (1) Pilot equipment: Details are shown in Table 21 below:

[0279] Table 21 Manufacturers of pilot equipment

[0280]

[0281] Note: Dextrin (production batch number 231116, Shaanxi Aoke Pharmaceutical Excipients Co., Ltd.) was used in the pilot test.

[0282] (2) Pilot method: The preparation method disclosed in Example 8 is followed, that is, 84 kg of the above 14 ingredients are added with 8 times the amount of water, soaked for 30 min, heated to boil for the first time, kept for 1 h after boiling, filtered, and 8 times the amount of water is added for the second time, heated to boil, kept for 1 h after boiling, filtered, and the two filtrates are combined. The combined liquid is concentrated to a clear paste with a relative density of 1.30 at 30°C, and dextrin is added. The ratio of dextrin to clear paste is 1:1.28; the mixed auxiliary materials are made into a soft material according to the standard of "holding into a ball and dispersing when lightly pressed", and the prepared soft material is prepared into granules by extrusion using a 14-mesh screen, and the prepared granules are placed at 70-75°C for drying. After drying for 1 h, they are sieved again using a 16-mesh screen and packaged.

[0283] (3) Pilot results: According to the requirements of the General Rules for Preparations (Chinese Pharmacopoeia 2020 Edition Part IV 0104 Granules), three batches of pilot samples were tested for particle size, moisture, solubility, filling volume difference, microbial limit, and content determination. The results are shown in Table 22 below:

[0284] Table 22 Pilot results of three batches of pilot samples

[0285]

[0286] By analyzing the data in Table 22, it can be found that the pilot process parameters of the Chinese medicine composition granules for treating herpetic neuralgia disclosed in Example 8 are stable, reliable, reasonable and stable.

[0287] Experimental Example 3

[0288] The Chinese medicine composition granules for treating herpetic neuralgia of the present invention were subjected to a neuralgia efficacy evaluation test, and the experimental method was carried out in sequence according to the following process 1 to process 5.

[0289] 1. Determine the experimental materials

[0290] 1. Reagents and medicines

[0291] (1) Resin toxin (batch number TC0309-230423) was purchased from Sichuan Jingcui Tiancheng Pharmaceutical Technology Co., Ltd.;

[0292] (2) Tween 80 (lot number 20150113);

[0293] (3) Anhydrous ethanol, purchased from Sinopharm Chemical Reagent Co., Ltd.;

[0294] (4) Pregabalin capsules (batch number H20203040), purchased from Qilu Pharmaceutical (Hainan) Co., Ltd.;

[0295] (5) 4% paraformaldehyde (lot number MA0192), purchased from Dalian Meilun Biotechnology Co., Ltd.;

[0296] (6) Pentobarbital sodium (batch number 030415) was purchased from Guangdong Taicheng Pharmaceutical Co., Ltd.;

[0297] (7) Normal saline, purchased from Shijiazhuang Siyao Co., Ltd.;

[0298] (8) The Chinese medicine composition granules for treating herpetic neuralgia of the present invention (batch number 20240126) are prepared by the preparation room of Wuxi Traditional Chinese Medicine Hospital.

[0299] 2. Instruments

[0300] (1) Aesthesio fiber filament type 514000-20C (Shanghai Yuyan Scientific Instrument Co., Ltd.);

[0301] (2) ZS-INP intelligent hot plate instrument (Beijing Zhongshidichuang Technology Development Co., Ltd.);

[0302] (1) Sorvall legend Micro21R low-temperature high-speed centrifuge (Thermo Fisher Scientific, USA);

[0303] (2) Milli-Q ultrapure water device (Millipore, USA).

[0304] 2. Animals

[0305] 50 male SD (Sprague-Dawley) rats, weighing 200-220 g, were purchased from Sprague Biotechnology (Suzhou) Co., Ltd., license number SCXK (Suzhou) 2022-0006. Animal husbandry conditions: temperature (24 ± 2) °C, humidity 60% ± 5%; free drinking water and food, adaptive feeding for 1 week. The animal experiments involved in this study strictly followed the various ethical management regulations on animal experiments of the Ethics Committee of the Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, and obtained approval documents (approval number 2024 (animal) -011).

[0306] 2. Determine the experimental method

[0307] 1. Establishment of herpetic neuralgia model: Establish a rat model of postherpetic neuralgia (PHN) induced by resin toxin (RTX). 10% Tween 80, 10% anhydrous ethanol and 0.9% saline were mixed, and RTX solution was prepared according to the ratio of 1 mg RTX and 10 ml solvent (1 ml Tween 80, 1 ml anhydrous ethanol, 8 ml saline), and fully dissolved by ultrasound. Each rat was intraperitoneally injected with 1 ml each time, once a day, for three consecutive days. Before and after modeling, the mechanical stimulation paw withdrawal threshold and thermal stimulation paw withdrawal latency of each rat were measured to confirm the success of the modeling.

[0308] 2. Animal grouping and administration: 50 male rats were randomly divided into a blank group (C), a model group (M), a pregabalin administration group (P, 13.5 mg·kg-1·d-1), a low-dose group of Chinese medicine composition granules for the treatment of herpes zoster neuralgia (L, 7.2 g·kg-1·d-1, 1 times the clinical equivalent dosage), and a high-dose group of Chinese medicine composition granules for the treatment of herpes zoster neuralgia (H, 10.8 g·kg-1·d-1, 1.5 times the clinical equivalent dosage), with 10 rats in each group. Except for the blank group, the PHN rat model was established in the other groups according to the above modeling method, and the blank group rats were injected with an equal dose of 0.9% saline by intraperitoneal vein. After the modeling was successful, the high-dose and low-dose groups of Chinese medicine composition granules for the treatment of herpes zoster neuralgia and the pregabalin administration group were gavaged, and the blank group and the model group were gavaged with an equal dose of 0.9% saline, and the gavage was continued for 14 days.

[0309] 3. Biological sample collection and disposal: After the last administration, the rats in each group were anesthetized with 10% chloral hydrate, and blood was collected from the abdominal aorta. The blood samples were kept at room temperature for 2 hours and rotated at 3500 r / min. -1 After centrifugation for 15 minutes, serum was collected and stored at -80°C. After blood collection, heart, liver, spleen, lung and kidney tissues were collected, washed with saline and fixed with 4% paraformaldehyde. The dorsal horn and dorsal root ganglion of the L4-L6 segment of the rat spinal cord were collected and stored at -80°C.

[0310] 4. Pharmacodynamic evaluation: The mechanical stimulation paw withdrawal threshold and thermal stimulation paw withdrawal latency were measured before and after modeling, 7 days and 14 days after administration.

[0311] (1) Determination of mechanical stimulation paw withdrawal threshold of rats: 5 transparent acrylic boxes (10cm×10cm×20cm with a hollow bottom) were placed side by side on a 1cm×1cm wire mesh rack, and 5 rats were placed each time. The rats were placed in the box to adapt for 5-10 minutes and reach a quiet state. Fibers with different pressure values ​​(0.4g, 0.6g, 1.4g, 2.0g, 4.0g, 6.0g, 10.0g, 15.0g) were used in order from small to large to vertically stimulate the skin on the outer edge of the plantar of the right hind limb of the rat from bottom to top (avoiding the foot pad and selecting the thin and tender skin). The intensity was gradually increased to a certain stimulation intensity, and the right hind foot was observed to see whether there was a contraction reaction (retraction, licking the foot, shaking the leg, etc.). The minimum stimulation intensity when the contraction reaction occurred was recorded as the mechanical stimulation paw withdrawal threshold (PWT).

[0312] (2) Determination of thermal stimulation paw withdrawal latency in rats: Set the temperature of the hot plate instrument to 55°C. After the temperature stabilizes, remove the plexiglass cover on the hot plate instrument, place the rat's hind paw on the hot plate, and step on the foot switch at the same time to start timing. When the rat is felt to have obvious evasive movements, step on the switch again to lock the time and record it as one thermal stimulation paw withdrawal latency. The average of the two paw withdrawal latencies is taken as the thermal stimulation paw withdrawal latency (PWL) of the rat. In order to avoid causing serious damage to the sole of the rat, the maximum exposure time for each exposure is set to 60 seconds. If the rat does not respond after more than 60 seconds, its foot should be immediately removed from the hot plate to avoid burns, and its paw withdrawal latency is calculated as 60 seconds.

[0313] 5. Elisa detection of inflammatory factors (TNF-α, IL-1β, IL-6) and pain factors (β-EP, CGPR) in rat serum

[0314] Rat serum samples were taken, and the standard and test samples were diluted according to the instructions of the kit. The OD values ​​were detected at 450nm absorbance on a microplate reader, and the serum TNF-α, IL-1β, IL-6, β-EP, and CGPR levels of rats in each group were calculated according to different OD values.

[0315] 6. Safety evaluation

[0316] The organs and tissues were fixed with 4% paraformaldehyde solution, rinsed overnight, dehydrated with 75% to 100% ethanol gradient series, and then embedded in paraffin to make 5μm slices. The slices were dewaxed once with xylene, soaked in anhydrous ethanol, 95% ethanol, 85% ethanol, and 75% ethanol in sequence, washed with tap water, and stained with hematoxylin-eosin (HE). The organs of the rats were observed under a microscope to evaluate their safety.

[0317] 3. Experimental Results

[0318] 1. Evaluation of the efficacy of Chinese medicine composite granules for the treatment of herpes zoster neuralgia in the treatment of PHN

[0319] (1) Mechanical stimulation paw withdrawal threshold determination: After RTX injection, the mechanical stimulation paw withdrawal threshold of the model group rats was significantly reduced compared with the blank group. After administration, compared with the model group, the paw withdrawal threshold of the high and low dosage groups of the Chinese medicine composition granules for treating herpetic neuralgia was significantly improved, while the model group showed a continuous decline. The specific results are shown in Table 23 below:

[0320] Table 23 PWT values ​​of rats in each group at different time points (mean ± SD, g, n = 6)

[0321]

[0322] Note: *p<0.05, **p<0.01, compared with the blank group; #p<0.05, ##p<0.01, ###p<0.001, compared with the model group.

[0323] (2) Determination of thermal stimulation paw withdrawal latency: After RTX injection, the thermal stimulation paw withdrawal latency of the model group rats was significantly prolonged compared with the blank group. After administration, compared with the model group, the thermal stimulation paw withdrawal latency of the high and low dosage groups of the Chinese medicine composition for treating herpes zoster neuralgia decreased significantly, while the model group continued to prolong. The specific results are shown in Table 24 below:

[0324] Table 24 PWL values ​​of rats in each group at different time points (mean ± SD, s, n = 6)

[0325]

[0326]

[0327] Note: *p<0.05, **p<0.01, ***p<0.001, compared with the blank group; #p<0.05, ##p<0.01, ###p<0.001, compared with the model group.

[0328] (3) Detection of TNF-α, IL-1β, IL-6, β-EP, and CGPR levels in rat serum: Compared with the blank group, the levels of TNF-α, IL-1β, IL-6, and CGPR in the model group were significantly increased (p < 0.01), and there was no statistically significant difference in β-EP level (p > 0.05). Compared with the model group, the levels of TNF-α, IL-6, and CGPR in the low-dose group of the Chinese medicine composition granules for the treatment of herpes zoster neuralgia were significantly reduced (p < 0.05); the levels of IL-6 and CGPR in the high-dose group of the Chinese medicine composition granules for the treatment of herpes zoster neuralgia were significantly reduced (p < 0.05). The levels of TNF-α, IL-6, and CGPR in the low-dose group of the Chinese medicine composition granules for the treatment of herpes zoster neuralgia were significantly reduced (p < 0.05); the levels of IL-6 and CGPR in the high-dose group of the Chinese medicine composition granules for the treatment of herpes zoster neuralgia were significantly reduced (p < 0.05), as shown in Table 25 below:

[0329] Table 25 Serum TNF-α, IL-1β, IL-6, β-EP, and CGPR levels in rats of each group (mean±SD, pg / ml, n=6)

[0330]

[0331]

[0332] Note: *p<0.05, **p<0.01, ***p<0.001, compared with the blank group; #p<0.05, ##p<0.01, ###p<0.001, compared with the model group.

[0333] (4) Preliminary safety evaluation: For the blank group (normal), model group (model), pregabalin administration group (P), low-dose group of Chinese medicine composition granules for treating herpes zoster neuralgia (ZYTL-L), and high-dose group of Chinese medicine composition granules for treating herpes zoster neuralgia (ZYTL-H), spleen, lung, liver, heart and kidney tissues of rats in each group were taken for pathological staining 14 days after administration. The results showed that high-dose and low-dose administration of Chinese medicine composition granules for treating herpes zoster neuralgia did not cause organ lesions in rats. The results are shown in Table 2. Figure 1 , indicating that the drug has good safety.

[0334] 4. Experimental Conclusion

[0335] A rat model of herpes zoster neuralgia induced by resin toxin was established. After high and low doses of Chinese medicine composition granules for the treatment of herpes zoster neuralgia, the mechanical stimulation paw withdrawal threshold of PHN rats was significantly increased, the thermal stimulation paw withdrawal latency was reduced, and the levels of inflammatory factors TNF-α, IL-6 and CGPR in PHN rats were significantly reduced. The above results show that the Chinese medicine composition granules for the treatment of herpes zoster neuralgia have a good pharmacodynamic effect on PHN. Pathological histological evaluation shows that the preparation has good safety.

[0336] The above is a detailed description of an embodiment of the present invention, but the content is only a preferred embodiment of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the patent coverage of the present invention.

Claims

1. A Chinese medicine composition for treating herpes zoster neuralgia, characterized in that: It is composed of the following components in parts by weight: 10-20 parts of stewed peach kernels, 10-20 parts of safflower, 10-20 parts of angelica, 15-30 parts of raw rehmannia, 5-20 parts of chuanxiong, 5-20 parts of red peony root, 10-20 parts of chuanxiong, 5-10 parts of platycodon, 5-10 parts of bupleurum, 5-10 parts of stir-fried aurantium with bran, 15-30 parts of vinegar corydalis, 15-30 parts of stir-fried spiny jujube kernels, 15-30 parts of Polygonum multiflorum, and 5-10 parts of liquorice.

2. A method for preparing a Chinese medicine composition for treating herpetic neuralgia according to claim 1, characterized in that: The steps include: Step 1: prepare and mix the raw material components according to the proportion, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep for 1 hour after boiling, and filter to obtain filter material 1 and filtrate 1; Step 2: add 8 times the amount of water to filter material 1, then heat and boil, keep boiling for 1 hour, filter to obtain filter material 2 and filtrate 2, combine filtrate 1 and filtrate 2 to obtain a Chinese medicine composition decoction for treating herpes zoster neuralgia.

3. A method for preparing a Chinese medicine composition for treating herpetic neuralgia according to claim 1, characterized in that: The steps include: Step 1: prepare and mix the raw material components according to the proportion, add 8 times the amount of water, soak for 30 minutes, then heat and boil, keep for 1 hour after boiling, and filter to obtain filter material 1 and filtrate 1; Step 2, adding 8 times the amount of water to the filter material 1, then heating and boiling, keeping it for 1 hour after boiling, filtering to obtain the filter material 2 and the filtrate 2, combining the filtrate 1 and the filtrate 2, and obtaining a Chinese medicine composition decoction for treating herpes zoster neuralgia; Step 3, concentrating the decoction into a clear paste, adding dextrin, stirring until the material becomes soft, granulating, drying, whole grains, and packaging to obtain the Chinese medicine composition granules for treating herpetic neuralgia.

4. The method for preparing the Chinese medicine composition for treating herpetic neuralgia according to claim 3, characterized in that: In step three, the relative density of the clear paste is 1.30 at 30°C.

5. The method for preparing the Chinese medicine composition for treating herpetic neuralgia according to claim 3, characterized in that: In step three, the amount of dextrin added is 1.28 times that of the clear paste.

6. The method for preparing the Chinese medicine composition for treating herpetic neuralgia according to claim 3, characterized in that: In step three, alcohol is added at the same time as dextrin, the mass fraction of the alcohol is 95%, and the amount of the alcohol added accounts for 2.5% of the total mass.

7. The method for preparing the Chinese medicine composition for treating herpetic neuralgia according to claim 3, characterized in that: In step three, the drying temperature is 70° C.-75° C., and the drying time is 1 hour.

8. Use of the Chinese medicine composition for treating herpetic neuralgia according to claim 1, characterized in that: Used to treat herpes zoster neuralgia.

9. The use of the Chinese medicine composition for treating herpetic neuralgia according to claim 8, characterized in that: The herpetic neuralgia includes subacute herpetic neuralgia and postherpetic neuralgia.

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