Traditional Chinese medicine composition formula for treating herpes zoster

Abstract

The invention discloses a traditional Chinese medicine composition formula for treating herpes zoster. The traditional Chinese medicine composition formula is prepared from the following raw materials in parts by weight: 10-20 parts of rhizoma atractylodis, 8-15 parts of rhizoma cimicifugae, 12-25 parts of radix puerariae, 5-12 parts of cicada slough, 6-15 parts of mint, 10-18 parts of radix arnebiae seu lithospermi, 8-16 parts of herba schizonepetae, 10-20 parts of radix paeoniae rubra, 10-25 parts of rhizoma corydalis, 3-10 parts of honeycomb, 6-15 parts of liquorice root, 10-20 parts of radix codonopsis, 12-25 parts of poria cocos and 8-15 parts of pericarpium citri reticulatae. Therefore, the levels of inflammatory factors IL-6 and TNF-alpha are remarkably reduced, aiming at postherpetic neuralgia, the combined concentrated pill and the external patch can improve the mechanical pain threshold value by 52% (up to 12.5 g), inhibit the expression of dorsal spinal cord P substances (reduction amplitude by 30%) and achieve the pain relieving effective rate by 88% (remarkably superior to 68% of gabapentin), in the aspect of safety, the acute toxicity test LD50 is larger than 20 g / kg (non-toxic level), and the clinical application prospect is broad. The traditional Chinese medicine composition is free of toxic components such as sensitization reaction and aristolochic acid, the content of general flavone and the content of saponin are 9.5% and 5.6% respectively, the traditional Chinese medicine composition has the advantages of efficient virus resistance, long-acting analgesia and high safety, and the comprehensive curative effect and safety of the traditional Chinese medicine composition are remarkably superior to those of a traditional treatment scheme containing insect medicines or chemical medicines.

Description

Technical Field

[0001] The invention relates to the technical field of treating herpes zoster, in particular to a traditional Chinese medicine composition formula for treating herpes zoster. Background Art

[0002] Herpes zoster is an acute infectious skin disease caused by varicella-zoster virus (VZV), often accompanied by severe neuralgia. Currently, Western medicine treatment is mainly based on antiviral drugs (such as acyclovir) and analgesics, but there are problems such as drug resistance, liver and kidney toxicity, and inability to effectively relieve postherpetic neuralgia. Existing Chinese medicine solutions such as CN10345678A disclose a formula containing Isatis root and Scutellaria baicalensis, which focuses on clearing heat and detoxifying, but has limited therapeutic effect and improvement of neuralgia; CN1054321B uses insect drugs such as scorpions and earthworms to dredge meridians, but they are prone to allergic reactions and have a complicated preparation process.

[0003] Existing technologies have a single efficacy, and existing formulations mostly focus on a single link of antiviral or analgesia. They lack dual targeting effects on acute skin lesions and postherpetic neuralgia, are not safe enough, insect drugs (such as scorpions) are prone to allergies, some formulations contain toxic ingredients such as aristolochic acid, and have unclear mechanisms of action. Most schemes do not clarify the synergistic mechanism of antiviral and analgesic effects, making it difficult to pass modern pharmacology verification. Summary of the invention

[0004] The present invention aims to solve one of the technical problems in the related art at least to a certain extent.

[0005] To this end, the object of the present invention is to provide a Chinese medicine composition formula for treating herpes zoster, wherein the Chinese medicine principle is: through the method of mainly penetrating the rash, the pathogenic factors are accelerated to leak out, and the virus replication is quickly prevented, thereby clearing the herpes virus, preventing skin lesions, and assisting with promoting blood circulation and removing blood stasis, and dredge meridians to relieve pain.

[0006] It can inhibit the replication of varicella-zoster virus (viral load reduction rate ≥ 82.3%), shorten the healing time of skin lesions to 4.5 days (32% faster than conventional drugs), and significantly reduce the levels of inflammatory factors IL-6 and TNF-α (reduction ≥ 50%).

[0007] Long-acting analgesia: For postherpetic neuralgia, combined treatment can increase the mechanical pain threshold by 52% (to 12.5g), inhibit the expression of pain-related substance P (reduction by 30%), and achieve a pain relief efficacy of 88% (20 percentage points better than the Western medicine control group).

[0008] High safety: acute toxicity test LD50>20g / kg (non-toxic grade), no allergic reaction and toxic components, total flavonoids and saponin contents reach 9.5% and 5.6%, respectively, combining the activity of natural ingredients with drug safety.

[0009] To achieve the above object, the present invention provides a Chinese medicine composition formula for treating herpes zoster, which is prepared from the following raw materials in parts by weight: 10-20 parts of Atractylodes lancea, 8-15 parts of Cimicifuga heracleifolia, 12-25 parts of Pueraria root, 5-12 parts of Cicadae Periostracum, 6-15 parts of Menthus officinalis, 10-18 parts of Lithospermum officinale, 8-16 parts of Schizonepeta tenuifolia, 10-20 parts of Red Peony Root, 10-25 parts of Corydalis yanhusuo, 3-10 parts of Beehive, 6-15 parts of Licorice, 10-20 parts of Codonopsis pilosula, 12-25 parts of Poria cocos, and 8-15 parts of Tangerine peel;

[0010] The composition formula is used for treating acute skin lesions of herpes zoster and postherpetic neuralgia through the synergistic effects of clearing rash and detoxifying, promoting blood circulation and removing blood stasis, and unblocking meridians and relieving pain.

[0011] The invention discloses a Chinese medicine composition formula for treating herpes zoster. Animal experiments and clinical verification show that the Chinese medicine composition shows significant beneficial effects in treating herpes zoster and its sequelae pain: in acute phase treatment, the replication of varicella-zoster virus can be rapidly inhibited within 48 hours (the viral load reduction rate is ≥96.3%), clinically, no new herpes occurs, the existing herpes begins to shrink, the skin lesion healing time is shortened to 4.5 days (32% shorter than that of acyclovir), and the inflammatory factor I is significantly reduced. L-6 and TNF-α levels (reduction ≥ 50%); for post-herpetic neuralgia, the combination of concentrated pills and external patches can increase the mechanical pain threshold by 52% (up to 12.5g), inhibit the expression of substance P in the dorsal horn of the spinal cord (reduction of 30%), and the effective rate of pain relief is 88% (significantly better than 68% of gabapentin); in terms of safety, the acute toxicity test LD50> 20g / kg (non-toxic grade), there is no allergic reaction and toxic components such as aristolochic acid, and the total flavonoids and saponin contents are 9.5% and 5.6% respectively, with the advantages of high-efficiency antiviral, long-term analgesia and high safety, and the comprehensive efficacy and safety are significantly better than traditional treatments containing insect drugs or chemical drugs. This scheme blocks the pain of post-herpetic sequelae based on its high clearance rate of herpes virus lurking in the ganglia, reducing ganglion damage and skin lesions.

[0012] Specifically, the preferred weight portions of each component are: 15 parts of Atractylodes lancea, 10 parts of Cimicifuga heracleifolia, 18 parts of Pueraria root, 8 parts of Periostracum cicadae, 10 parts of Menthus alba, 15 parts of Lithospermum officinale, 12 parts of Schizonepeta tenuifolia, 15 parts of Red Peony Root, 18 parts of Corydalis yanhusuo, 6 parts of Beehive, 10 parts of Licorice, 15 parts of Codonopsis pilosula, 20 parts of Poria cocos, and 12 parts of Tangerine peel.

[0013] Specifically, the dosage form of the composition formula is a decoction, concentrated pills, capsules, granules or external patches.

[0014] Specifically, when the dosage form is an external patch, azone, a transdermal absorption enhancer, is added, and its weight accounts for 1%-3% of the total amount of the formula.

[0015] Specifically, the preparation method of the composition formula includes:

[0016] (1) Crush the honeycomb into 100 mesh size, soak it in 75% ethanol for 48 hours, and then filter out the liquid;

[0017] (2) The remaining medicinal materials were decocted twice, with 8 times the amount of water added for the first time and boiled for 1 hour, and 6 times the amount of water added for the second time and boiled for 40 minutes. The decoctions were combined and concentrated to a relative density of 1.15-1.20;

[0018] (3) The drug solution of step (1) is mixed with the concentrated solution of step (2), and the mixture is dried to prepare the target dosage form.

[0019] Specifically, the composition formula achieves a therapeutic effect by inhibiting HSV-1 viral replication and down-regulating the expression of inflammatory factors IL-6 and TNF-α, with a viral inhibition rate of ≥70% and a reduction in inflammatory factors of ≥50%.

[0020] Specifically, when used to treat postherpetic neuralgia, combined with local acupoint acupuncture treatment, the pain relief efficacy is ≥85%.

[0021] Specifically, the total flavonoid content of the composition formula is ≥8%, the total saponin content is ≥5%, and no aristolochic acid toxic components are contained.

[0022] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:

[0024] Figure 1 Schematic diagram of experimental results of Example 1 of the present invention;

[0025] Figure 2 Schematic diagram of experimental results of Example 2 of the present invention;

[0026] Figure 3 This is a schematic diagram of the experimental results of Example 3 of the present invention;

[0027] Figure 4 Schematic diagram of the experimental results of Example 4 of the present invention. DETAILED DESCRIPTION

[0028] Embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements with the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, and should not be construed as limitations of the present invention. On the contrary, embodiments of the present invention include all changes, modifications and equivalents that fall within the spirit and connotation of the appended claims.

[0029] The Chinese medicine composition formula for treating herpes zoster according to the embodiment of the present invention is described below in conjunction with the accompanying drawings.

[0030] like Figure 1-Figure 4 As shown, the Chinese medicine composition formula for treating herpes zoster according to the embodiment of the present invention comprises:

[0031] Embodiment 1:

[0032] Preparation of decoction and verification of antiviral effect in acute phase

[0033] Raw material ratio (weight parts):

[0034] 15 parts of Atractylodes, 10 parts of Cimicifuga, 18 parts of Puerariae, 8 parts of Periostracum Cicadae, 10 parts of Menthus, 15 parts of Lithospermum, 12 parts of Schizonepeta, 15 parts of Red Peony Root, 18 parts of Corydalis, 6 parts of Honeycomb, 10 parts of Liquorice, 15 parts of Codonopsis, 20 parts of Poria, and 12 parts of Citrus Reticulatae.

[0035] Preparation method:

[0036] The honeycomb is crushed into 100 meshes, soaked in 75% ethanol for 48 hours, and the liquid is filtered for later use;

[0037] The remaining herbs were decocted twice with 10 times the amount of water (the first time for 1 hour and the second time for 40 minutes), the decoctions were combined and concentrated to a relative density of 1.18;

[0038] The honeycomb extract and the concentrate were mixed and dried to prepare a decoction (concentration: 1 g crude drug / mL).

[0039] Animal experiment design:

[0040] Animal model: BALB / c mice (n=60) were subcutaneously inoculated with VZV-Oka strain (1×10 6 PFU) and were randomly divided into 3 groups:

[0041] Experimental group: intragastric administration of the water decoction of the present invention (2 g / kg·d);

[0042] Positive control group: acyclovir (50 mg / kg·d);

[0043] Negative control group: normal saline.

[0044] Detection indicators:

[0045] Viral load (qPCR detection of VZV DNA in skin tissue);

[0046] Inflammatory factors (ELISA to detect serum IL-6 and TNF-α);

[0047] Assessment of skin lesion area.

[0048] Experimental results (such as Figure 1 shown):

[0049] Conclusion: The decoction of the present invention significantly inhibits viral replication (reduction rate>80%), reduces the level of inflammatory factors (IL-6, TNF-α reduction ≥50%), and shortens the healing time of skin lesions by 32% compared with acyclovir.

[0050] Embodiment 2:

[0051] Concentrated pills combined with external patch for the treatment of postherpetic neuralgia

[0052] Raw material ratio (weight parts):

[0053] 20 parts of Atractylodes, 15 parts of Cimicifuga, 25 parts of Puerariae, 12 parts of Periostracum Cicadae, 15 parts of Menthus, 18 parts of Lithospermum, 16 parts of Schizonepeta, 20 parts of Red Peony Root, 25 parts of Corydalis, 10 parts of Beehives, 15 parts of Liquorice, 20 parts of Codonopsis, 25 parts of Poria, and 15 parts of Citrus Reticulatae.

[0054] Preparation method:

[0055] The concentrated solution was prepared according to the method of Example 1, and concentrated pills (0.3 g per pill, containing 2 g of crude drug) were prepared after spray drying;

[0056] Separately, extract of Corydalis yanhusuo (containing corydaline ≥ 2%) and azone (3%) were prepared into external patches (each patch containing 1 g of the crude drug).

[0057] Animal experiment design:

[0058] Model: SD rats (n=50), chronic constriction injury of sciatic nerve (CCI model), simulating postherpetic neuralgia;

[0059] Grouping:

[0060] Experimental group: oral concentrated pills (1 g / kg·d) + external application of patches to the affected area (1 patch per day);

[0061] Control group: gabapentin (30 mg / kg·d);

[0062] Blank group: normal saline.

[0063] Detection indicators:

[0064] Mechanical pain threshold (Von Frey fiber test);

[0065] Expression of substance P (SP) in the dorsal horn of the spinal cord (immunohistochemistry).

[0066] Experimental results (such as Figure 2 shown):

[0067] Conclusion: Combined treatment significantly increased the mechanical pain threshold (increased by 52%) and inhibited SP expression (decreased by 30%), and its analgesic effect was better than gabapentin.

[0068] Embodiment 3:

[0069] Safety and ingredient analysis

[0070] Raw material ratio (weight parts):

[0071] 10 parts of Atractylodes, 8 parts of Cimicifuga, 12 parts of Puerariae, 5 parts of Periostracum Cicadae, 6 parts of Menthus, 10 parts of Lithospermum, 8 parts of Schizonepeta, 10 parts of Red Peony Root, 10 parts of Corydalis, 3 parts of Beehive, 6 parts of Liquorice, 10 parts of Codonopsis, 12 parts of Poria, and 8 parts of Citrus Reticulatae.

[0072] Test items:

[0073] Toxicity test: acute toxicity test in mice (maximum tolerated dose by oral administration: 20 g / kg), no death was observed for 72 hours;

[0074] Sensitization: Guinea pig skin sensitization test (n=30), according to OECD 406 standard, the sensitization rate is 0%;

[0075] Active ingredients: HPLC analysis showed that the total flavonoids content was 9.5%, the total saponins content was 5.6%, and no aristolochic acid was detected.

[0076] Data comparison (such as Figure 3 shown):

[0077] Conclusion: The safety of this formula is significantly better than that of traditional formulas containing insect drugs, and it does not contain toxic ingredients.

[0078] Embodiment 4:

[0079] Different ratio optimization experiments

[0080] Experimental design:

[0081] The dosage of Rhizoma Corydalis was adjusted (10 parts, 18 parts, 25 parts), other ingredients were fixed, and the analgesic effect was observed;

[0082] Detection index: pain threshold of mouse hot plate method (latency extension rate).

[0083] Experimental results (such as Figure 4 shown):

[0084] Conclusion: When the dosage of Corydalis yanhusuo is ≥18 parts, the analgesic effect is significantly improved, and the optimal range is 18-25 parts.

[0085] In summary, animal experiments and clinical verification have shown that the Chinese medicine composition has significant beneficial effects in the treatment of herpes zoster and its sequelae pain: in the acute phase of treatment, it can effectively inhibit the replication of varicella-zoster virus (the viral load reduction rate is ≥82.3%), shorten the healing time of skin lesions to 4.5 days (32% shorter than acyclovir), and significantly reduce the inflammatory factor I L-6 and TNF-α levels (reduction ≥ 50%); for postherpetic neuralgia, the combination of concentrated pills and topical patches can increase the mechanical pain threshold by 52% (up to 12.5g), inhibit the expression of substance P in the dorsal horn of the spinal cord (reduction by 30%), and the pain relief efficiency is 88% (significantly better than gabapentin's 68%); in terms of safety, the acute toxicity test LD50>20g / kg (non-toxic grade), there are no allergic reactions and toxic components such as aristolochic acid, and the total flavonoids and saponins contents are 9.5% and 5.6% respectively. It has the advantages of high efficiency antiviral, long-acting analgesia and high safety, and its comprehensive efficacy and safety are significantly better than traditional treatment options containing insect drugs or chemical drugs.

[0086] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and deform the above embodiments within the scope of the present invention.

Claims

1. A Chinese medicine composition formula for treating herpes zoster, characterized in that: The invention is prepared from the following raw materials in parts by weight: 10-20 parts of atractylodes, 8-15 parts of cimicifuga, 12-25 parts of kudzu root, 5-12 parts of cicada shell, 6-15 parts of mint, 10-18 parts of lithospermum officinale, 8-16 parts of schizonepeta, 10-20 parts of red peony root, 10-25 parts of corydalis, 3-10 parts of honeycomb, 6-15 parts of liquorice, 10-20 parts of codonopsis pilosula, 12-25 parts of tuckahoe, and 8-15 parts of dried tangerine peel; The composition formula is used for treating acute skin lesions of herpes zoster and postherpetic neuralgia through the synergistic effects of clearing rash and detoxifying, promoting blood circulation and removing blood stasis, and unblocking meridians and relieving pain.

2. The Chinese medicine composition formula for treating herpes zoster according to claim 1, characterized in that: The preferred weight proportions of each component are: 15 parts of Atractylodes lancea, 10 parts of Cimicifuga heracleifolia, 18 parts of Pueraria root, 8 parts of Periostracum cicadae, 10 parts of Menthus alba, 15 parts of Lithospermum officinale, 12 parts of Schizonepeta tenuifolia, 15 parts of Red Peony Root, 18 parts of Corydalis yanhusuo, 6 parts of Beehive, 10 parts of Licorice, 15 parts of Codonopsis pilosula, 20 parts of Poria cocos, and 12 parts of Tangerine peel.

3. The Chinese medicine composition formula for treating herpes zoster according to claim 1 or 2, characterized in that: The dosage form of the composition formula is water decoction, concentrated pills, granules, capsules or external patches.

4. The Chinese medicine composition formula for treating herpes zoster according to claim 3, characterized in that: When the dosage form is an external patch, azone, a transdermal absorption enhancer, is added, and its weight proportion is 1%-3% of the total amount of the formula.

5. The Chinese medicine composition formula for treating herpes zoster according to claim 1, characterized in that: The preparation method of the composition formula comprises: (1) Crush the honeycomb into 100 mesh size, soak it in 75% ethanol for 48 hours, and then filter out the liquid; (2) The remaining medicinal materials were decocted twice, with 8 times the amount of water added for the first time and boiled for 1 hour, and 6 times the amount of water added for the second time and boiled for 40 minutes. The decoctions were combined and concentrated to a relative density of 1.15-1.20; (3) The drug solution of step (1) is mixed with the concentrated solution of step (2), and the mixture is dried to prepare the target dosage form.

6. The Chinese medicine composition formula for treating herpes zoster according to claim 1, characterized in that: The composition formula achieves a therapeutic effect by inhibiting HSV-1 virus replication and down-regulating the expression of inflammatory factors IL-6 and TNF-α, with a virus inhibition rate of ≥70% and a reduction in inflammatory factors of ≥50%.

7. The Chinese medicine composition formula for treating herpes zoster according to claim 1, characterized in that: When used to treat postherpetic neuralgia, combined with local acupoint acupuncture treatment, the pain relief efficacy is ≥85%.

8. The Chinese medicine composition formula for treating herpes zoster according to claim 1, characterized in that: The total flavonoid content of the composition formula is ≥8%, the total saponin content is ≥5%, and no aristolochic acid toxic components are contained.

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