An analgesic patch containing radix scophulariae and radix aconiti and a preparation method thereof

Abstract

The application discloses a painkilling preparation containing radix scophulariae and radix aconiti and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine. The preparation is a transdermal patch, which is composed of a backing layer, a drug depot layer and an anti-sticking layer. The drug depot layer contains traditional Chinese medicine active ingredients and patch auxiliaries such as pressure-sensitive adhesive and transdermal absorption accelerators. The traditional Chinese medicine active ingredients take radix scophulariae and radix aconiti as the core drug pair, and are supplemented with one or more of the following drugs: qi-regulating analgesic drugs, blood-removing qi-regulating drugs, blood-activating analgesic drugs, blood-stasis-removing analgesic drugs, warm-qi-activating cold-dispelling drugs, wind-dispelling cold-dispelling drugs and external analgesic drugs. The application is a modern traditional Chinese medicine external preparation prepared by a patch technology, and the drug can penetrate the skin and directly reach the lesion, thereby playing a therapeutic role on inflammatory pain, cancer pain and idiopathic pain. The preparation has the characteristics of large drug loading, good transdermal absorption, fast analgesic effect, long-acting effect and avoidance of oral toxicity risk.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine pharmaceutical technology, specifically relating to an analgesic transdermal patch with toad venom and Aconitum carmichaelii as the core drug pair, as well as the preparation method and application of the patch. Background Technology

[0002] Pain is a common clinical symptom that severely impacts patients' quality of life. Currently, clinical treatment of pain primarily relies on nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. However, long-term use of NSAIDs can easily cause side effects such as gastrointestinal reactions and liver and kidney damage; opioids, on the other hand, can lead to addiction, respiratory depression, nausea, and vomiting. Furthermore, oral administration results in the first-pass effect in the liver, leading to reduced drug bioavailability and difficulty in maintaining stable blood drug concentrations, thus failing to meet the need for continuous analgesia.

[0003] Traditional Chinese medicine external patches are absorbed through the skin, allowing the medication to directly reach the affected area. This avoids the first-pass effect of the liver and the inactivation effect of the gastrointestinal tract, offering advantages such as high local drug concentration, minimal systemic toxicity, and ease of use, making them an important means of pain management. Toad venom, a traditional Chinese medicine, has detoxifying, analgesic, and mind-clearing effects. Modern pharmacological research shows that toad venom contains active ingredients such as bufotoxin and bufotoxin base, exhibiting significant central and peripheral analgesic effects. Aconitum carmichaelii excels at dispelling wind and dampness, warming the meridians, and relieving pain. Its main active ingredient, aconitine alkaloids, can stimulate sensory nerve endings, initially producing a warming sensation followed by an anesthetic and analgesic effect, making it particularly effective for cold-related pain and rheumatic pain.

[0004] Although both toad venom and aconite have strong analgesic effects, they are also highly toxic, and using them alone in large doses carries significant risks. According to the traditional Chinese medicine principle of "mutual reinforcement," combining drugs with similar properties and effects can enhance their efficacy and reduce toxicity. Currently, while there are reports of single-herb preparations of toad venom or aconite, there is no complete technical solution that uses toad venom and aconite as the core drug pair, combined with other traditional Chinese medicines that promote qi circulation, relieve pain, break up blood stasis, and warm the interior to prepare a modern transdermal patch for treating various types of pain. Therefore, developing a compound traditional Chinese medicine patch with high drug loading, good transdermal absorption, rapid analgesic onset, and high safety is of significant clinical importance. Summary of the Invention

[0005] The purpose of this invention is to provide a transdermal patch containing toad venom and aconite, and its preparation method. The patch obtained by this invention uses toad venom and aconite as the core medicinal pair, working synergistically. Through the rational combination of multiple traditional Chinese medicines, and via transdermal administration, it significantly enhances the analgesic effect while reducing the risk of oral toxicity. This patch has advantages such as rapid onset of action, long-lasting effect, low irritation, and ease of use, and has excellent prospects for clinical application.

[0006] To achieve the above-mentioned technical effects, the present invention is implemented through the following measures:

[0007] This invention first discloses a traditional Chinese medicine composition containing toad venom and aconite root analgesic patch, comprising, by weight percentage:

[0008] Toad venom 0.1-10%, Aconitum carmichaelii 5-98%, heat-clearing and swelling-reducing drugs 0-20%, qi-regulating and pain-relieving drugs 0-30%, blood-breaking and qi-regulating drugs 0-20%, blood-activating and pain-relieving drugs 0-30%, warming and cold-dispersing drugs 0-20%, wind-dispelling and cold-dispersing drugs 0-20%.

[0009] Furthermore, the toad venom is toad venom or wine-processed toad venom, and the aconite is raw or processed aconite; the heat-clearing and swelling-reducing medicine is one or more of Paris polyphylla, Hibiscus leaf, dandelion, and Viola yedoensis; the qi-regulating and pain-relieving medicine is one or more of Zanthoxylum nitidum, Nardostachys jatamansi, Aucklandia lappa, and Corydalis yanhusuo; the blood-breaking and qi-regulating medicine is one or more of Curcuma zedoaria, Sparganium, and Curcuma longa; the blood-activating and pain-relieving medicine is one or more of Boswellia carterii, Carthamus tinctorius, Myrrh, Ligusticum chuanxiong, and Panax notoginseng; the warming and cold-dispersing medicine is one or more of Cinnamomum cassia, Piper longum, Kaempferia galanga, Syzygium aromaticum, and Zingiber officinale; and the wind-dispelling and cold-dispersing medicine is one or more of Asarum heterotropoides, Ephedra sinica, Aconitum carmichaelii, Notopterygium incisum, and Angelica pubescens.

[0010] Furthermore, the toad venom is toad venom, and the aconite is raw aconite.

[0011] The present invention also discloses an analgesic preparation comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable patch excipients.

[0012] Furthermore, the drug-approved patch excipients include: matrix material, moisturizer, transdermal absorption enhancer, backing material, and anti-adhesion material.

[0013] Furthermore, the analgesic is in the form of a patch, which consists of, from top to bottom: a backing layer, a drug reservoir layer, and an anti-adhesion layer.

[0014] Furthermore, the matrix material is one or more of polyvinyl alcohol, sodium carboxymethyl cellulose, glyceryl laurate, and hydroxypropyl methylcellulose; the moisturizer is one or more of glycerin, ethanol, or ethylene glycol; and the transdermal absorption enhancer is one or more of menthol, borneol, camphor, methyl salicylate, methanol, dimethyl sulfoxide, and azone.

[0015] Furthermore, the transdermal absorption enhancer is prepared by mixing camphor, azone, and propylene glycol in a weight ratio of 1:1~2:1~3.

[0016] The present invention also discloses a method for preparing any of the above-described analgesic agents, comprising:

[0017] The toad venom was pretreated to obtain pretreated toad venom for later use.

[0018] Aconitum carmichaelii, heat-clearing and swelling-reducing drugs, qi-regulating and pain-relieving drugs, blood-breaking and qi-regulating drugs, blood-activating and pain-relieving drugs, warming and cold-dispelling drugs, and wind-dispelling and cold-dispelling drugs are pulverized separately, heated with ethanol and refluxed three times, filtered, the filtrates are combined, and concentrated under reduced pressure to obtain a fluid extract.

[0019] The pretreated toad venom was incorporated into the fluid extract, the matrix material was fully swollen, and humectants and transdermal absorption enhancers were added and stirred evenly.

[0020] The above-mentioned active ingredients of traditional Chinese medicine are added to the matrix adhesive, stirred evenly, coated on the backing material, covered with an anti-sticking layer, and after drying and cutting, an analgesic preparation is obtained.

[0021] Furthermore, the toad venom pretreatment is selected from any of the following:

[0022] Toad venom is extracted twice by reflux with 90% ethanol, the reflux liquids are combined and concentrated to dryness for later use; or toad venom is pulverized to obtain toad venom powder for later use.

[0023] Furthermore, the drying conditions are vacuum drying at 30~60℃ for 10~30 minutes.

[0024] Prescription Explanation

[0025] This invention is based on the traditional Chinese medicine theory of pain syndrome, namely, "pain arises from obstruction and lack of nourishment." It targets pain caused by the interplay of cold, toxins, blood stasis, and stagnation, establishing a treatment principle of "warming yang and dispelling cold, detoxifying and opening the orifices, promoting blood circulation and qi flow, and unblocking the meridians and relieving pain." The entire formula uses toad venom and aconite as the principal herbs, working synergistically to directly target the root of the disease. It is supplemented with heat-clearing and swelling-reducing herbs, qi-regulating and pain-relieving herbs, blood-breaking and qi-regulating herbs, blood-activating and pain-relieving herbs, warming and cold-dispelling herbs, and wind-dispelling herbs. The comprehensive formula works synergistically to exert a multi-target, multi-pathway analgesic effect.

[0026] The patch prepared from the traditional Chinese medicine composition mainly exerts analgesic effects for external use. These analgesic effects include relief from various types of pain, such as peripheral pain, central pain, pricking pain, chemical irritation pain, nerve compression pain, and tumor pain.

[0027] Compared with the prior art, the present invention has the following outstanding advantages:

[0028] (1) Synergistic analgesic effect: This invention uses toad venom and aconite as the core drug pair, which complement each other, and is supplemented with a variety of Chinese medicines that promote blood circulation, regulate qi, warm the interior, dispel wind, and clear heat, forming a synergistic network of multiple components and multiple targets. Pharmacodynamic experiments have confirmed that the whole formula patch has a significant inhibitory effect on acetic acid-induced writhing response in mice, and the effect is better than that of single herbs or simple combinations.

[0029] (2) Broad analgesic spectrum: The patch of this invention can effectively combat various types of pain, such as inflammatory pain, cancer pain, and neuropathic pain, and is especially suitable for pain syndrome of cold coagulation and blood stasis type.

[0030] (3) Significantly reduced toxicity: This invention uses a transdermal drug delivery method, where the drug is delivered directly to the lesion through the skin, avoiding the first-pass effect of the liver and gastrointestinal irritation of oral preparations, and significantly reducing the systemic toxicity risk of toxic traditional Chinese medicines such as toad venom and aconite. At the same time, the patch is convenient to use and can be removed at any time, improving the safety of clinical drug use.

[0031] (4) Excellent pharmaceutical properties: By selecting the best matrix materials and transdermal absorption enhancers, this invention exhibits good adhesion, heat resistance, and excipient properties, with stable and controllable quality. The addition of transdermal absorption enhancers significantly improves the transdermal penetration rate of the active ingredients, ensuring rapid onset of action and sustained release.

[0032] (5) Good patient compliance: This invention is a topical dosage form with a low frequency of administration (once a day), does not stain clothing, and is easy to use. It is especially suitable for patients with chronic pain who need long-term analgesia, and significantly improves patients' medication compliance. Attached Figure Description

[0033] Figure 1 This is a schematic diagram of the layered structure of the analgesic transdermal patch of the present invention.

[0034] Figure 2 The effect of the patch of the present invention on the expression of GFAP in the spinal cord of S180 tumor compression pain model mice; wherein: A-normal group, B-model group, C-Example 1, D-Example 2, E-Example 3, F-Example 4, G-Example 5, H-Example 6, I-Example 7, J-Example 8.

[0035] Figure 3 The effect of the patch of the present invention on CD11b expression in the spinal cord of S180 tumor compression pain model mice; wherein: A-normal group, B-model group, C-Example 1, D-Example 2, E-Example 3, F-Example 4, G-Example 5, H-Example 6, I-Example 7, J-Example 8. Detailed Implementation

[0036] The present invention will be further described below with reference to embodiments, but the scope of protection of the present invention is not limited thereto.

[0037] Example 1:

[0038] 3.2g toad venom, 96.8g raw aconite root

[0039] Toad venom was extracted twice by reflux with 90% ethanol. The reflux liquids were combined and concentrated to dryness. The remaining Chinese medicinal materials were appropriately pulverized, extracted three times by reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. 10g of polyvinyl alcohol was added to an appropriate amount of water and allowed to swell fully. Then, 1.5g of glycerin, 6g of azone, 8g of propylene glycol, and 6g of camphor were added and stirred evenly. The above Chinese medicinal extracts were added to the matrix, stirred evenly, coated onto the backing material, covered with an anti-adhesive layer, and vacuum dried at 30℃ for 60 minutes. The resulting 4.5cm × 8cm patches were then cut.

[0040] Example 2:

[0041] Toad venom 2g, processed aconite root 30g, Zanthoxylum nitidum 12g, Curcuma zedoaria 10g, frankincense 15g, myrrh 15g, Asarum sieboldii 8g, cinnamon 8g

[0042] The toad venom was pulverized into a fine powder. The remaining Chinese medicinal herbs were appropriately pulverized, extracted three times by heating under reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. The toad venom powder was added to the above fluid extract and mixed thoroughly. 7g of polyvinyl alcohol and 3.5g of sodium carboxymethyl cellulose were added to an appropriate amount of water and allowed to swell completely. Then, 1.5g of glycerin, 3g of camphor, 4g of methyl salicylate, 3g of azone, and 10g of propylene glycol were added and stirred thoroughly. The above herbal extract was added to the base adhesive solution and stirred thoroughly. The mixture was then coated onto the backing material, covered with an anti-adhesive layer, and vacuum dried at 45℃ for 30 minutes. The resulting patch was then cut to a size of 4.5cm × 8cm.

[0043] Example 3:

[0044] 1.5g of toad venom, 25g of prepared aconite root, 5g of Zanthoxylum nitidum, 4g of Paris polyphylla, 4.2g of raw Aconitum carmichaelii, 4g of Hibiscus mutabilis leaf, 4g of Sparganium stoloniferum, 4g of Curcuma zedoaria, 5g of Carthamus tinctorius, 5g of clove, 4.2g of Asarum heterotropoides, 5g of cinnamon, 4.2g of Hemp seed, 5g of Piper longum, 5g of Nardostachys jatamansi, 5g of Kaempferia galanga, 5g of frankincense, 5g of myrrh.

[0045] The toad venom was pulverized into a fine powder. The remaining Chinese medicinal herbs were appropriately pulverized, extracted three times by heating under reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. The toad venom powder was added to the above fluid extract and mixed thoroughly. 7g of polyvinyl alcohol and 3.5g of sodium carboxymethyl cellulose were added to an appropriate amount of water and allowed to fully swell. Then, 1.5g of glycerin, 3g of menthol, 3g of borneol, 7g of camphor, 3g of methyl salicylate, 2g of benzyl alcohol, and 2g of dimethyl sulfoxide were added and stirred thoroughly. The above herbal extracts were added to the matrix and stirred thoroughly. The mixture was then coated onto a backing material, covered with an anti-adhesive layer, and vacuum dried at 40℃ for 20 minutes. The resulting patch, measuring 4.5cm × 8cm, was then cut.

[0046] Example 4:

[0047] 2g of toad venom, 35g of raw aconite, 15g of Paris polyphylla, 10g of Zanthoxylum nitidum, 8g of Sparganium stoloniferum, 10g of safflower, 10g of myrrh, 5g of Piper longum, and 5g of Asarum heterotropoides.

[0048] Toad venom was extracted twice by reflux with 90% ethanol. The reflux liquids were combined and concentrated to dryness. The remaining Chinese medicinal materials were appropriately pulverized, extracted three times by reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. 10g of polyvinyl alcohol was added to an appropriate amount of water and allowed to swell fully. Then, 1.5g of glycerin, 8g of camphor, 4g of menthol, and 8g of azone were added and stirred evenly. The above Chinese medicinal extracts were added to the matrix, stirred evenly, coated onto the backing material, covered with an anti-adhesive layer, and vacuum dried at 60℃ for 15 minutes. The resulting 4.5cm × 8cm patches were then cut.

[0049] Example 5:

[0050] Toad venom 1.8g, raw aconite root 32g, Paris polyphylla 10g, Nardostachys chinensis 8g, Sparganium stoloniferum 8g, frankincense 12g, myrrh 12g, galangal 6g, clove 6g, and sesame seeds 4.2g.

[0051] The toad venom was pulverized into a fine powder. The remaining Chinese medicinal herbs were appropriately pulverized, extracted three times by heating under reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. The toad venom powder was added to the above fluid extract and mixed thoroughly. 7g of polyvinyl alcohol and 3.5g of sodium carboxymethyl cellulose were added to an appropriate amount of water and allowed to swell completely. Then, 1.5g of glycerin, 6g of borneol, 6g of camphor, and 8g of azone were added and stirred thoroughly. The above herbal extract was added to the matrix and stirred thoroughly. The mixture was then coated onto a backing material, covered with an anti-adhesive layer, and vacuum dried at 30℃ for 30 minutes. The resulting patch, measuring 4.5cm × 8cm, was then cut.

[0052] Example 6:

[0053] Toad venom 2.5g, raw aconite root 35g, hibiscus leaf 7g, zedoaria root 18g, turmeric root 8g, frankincense 7g, myrrh 7g, cinnamon 7g, long pepper 7g, raw aconite root 3.5g

[0054] The toad venom was pulverized into a fine powder. The remaining Chinese medicinal herbs were appropriately pulverized, extracted three times by heating under reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. The toad venom powder was added to the above fluid extract and mixed thoroughly. 7g of polyvinyl alcohol and 3.5g of sodium carboxymethyl cellulose were added to an appropriate amount of water and allowed to swell completely. Then, 1.5g of glycerin, 6g of methyl salicylate, 5g of menthol, and 8g of azone were added and stirred thoroughly. The above herbal extracts were added to the matrix and stirred thoroughly. The mixture was then coated onto a backing material, covered with an anti-adhesive layer, and vacuum dried at 30℃ for 30 minutes. The resulting patch, measuring 4.5cm × 8cm, was then cut.

[0055] Example 7:

[0056] Toad venom 2g, raw aconite root 28g, hibiscus leaf 8g, zedoaria root 10g, turmeric root 10g, sparganium rhizome 10g, safflower 8g, myrrh 8g, long pepper 5g, galangal 5g, asarum root 3g, *Hypericum perforatum* 3g

[0057] The toad venom was pulverized into a fine powder. The remaining Chinese medicinal materials were appropriately pulverized, extracted three times by heating under reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. The toad venom powder was added to the above fluid extract and mixed thoroughly. 7g of polyvinyl alcohol and 3.5g of sodium carboxymethyl cellulose were added to an appropriate amount of water and allowed to swell completely. Then, 1.5g of glycerin, 10g of camphor, 4g of benzyl alcohol, and 6g of methyl salicylate were added and stirred thoroughly. The above Chinese medicinal extract was added to the base adhesive solution and stirred thoroughly. This mixture was then coated onto the backing material, covered with an anti-adhesive layer, and vacuum dried at 40℃ for 30 minutes. The resulting patch, measuring 4.5cm × 8cm, was then cut.

[0058] Example 8:

[0059] Toad venom 1.5g, raw aconite root 30g, Paris polyphylla 10g, Zanthoxylum nitidum 12g, Nardostachys jatamansi 12g, Curcuma zedoaria 8g, frankincense 8g, myrrh 8g, cinnamon 5.5g, raw Aconitum carmichaelii 5g

[0060] The toad venom was pulverized into a fine powder. The remaining Chinese medicinal herbs were appropriately pulverized, extracted three times by heating under reflux with 90% ethanol, filtered, and the filtrates were combined and concentrated under reduced pressure to obtain a fluid extract. The toad venom powder was added to the above fluid extract and mixed thoroughly. 7g of polyvinyl alcohol and 3.5g of sodium carboxymethyl cellulose were added to an appropriate amount of water and allowed to swell completely. Then, 1.5g of glycerin, 6g of camphor, 6g of menthol, and 8g of methyl salicylate were added and stirred thoroughly. The above herbal extracts were added to the base adhesive solution and stirred thoroughly. The mixture was then coated onto the backing material, covered with an anti-adhesive layer, and vacuum dried at 30℃ for 30 minutes. The resulting patch, measuring 4.5cm × 8cm, was then cut.

[0061] Experimental Example 1

[0062] Pharmacological properties of the analgesic preparations obtained in each group of examples

[0063] The results, including the determination of properties, adhesiveness, and bufotoxin content, are shown in Table 1.

[0064] (1) Adhesion performance test

[0065] The adhesive properties of the patches described in Examples 1-8 were tested using the rolling ball ramp stop method according to the method for determining adhesion under General Chapter 0952 of Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0066] (2) In vitro transdermal test

[0067] The transdermal performance of the patches described in Examples 1-8 was compared. Using a modified Franz diffusion cell, isolated rat skin was used as a skin model, and naphthalene was used as an internal standard. The camphor content in the receiving solution after 24 h was detected by GC-MS, and the cumulative permeation was calculated.

[0068] (3) Content determination

[0069] The content of toad venom base in the patches described in Examples 1-8 was determined. HPLC was used with a C18 column and a mobile phase of 0.3% acetic acid-water-acetonitrile (50:50); the detection wavelength was 296 nm.

[0070] Table 1. Pharmaceutical properties of the patch of the present invention

[0071]

[0072] Experimental Example 2

[0073] The analgesic activity of the analgesic preparations obtained in each group of examples was determined, and the specific results are shown in Table 2.

[0074] (1) Acetic acid writhing test

[0075] The peripheral analgesic activity of the patches described in Examples 1-8 was evaluated using an acetic acid-induced writhing model in mice. Kunming mice were treated daily with patches (1.5 cm × 1.5 cm) applied to the shaved abdominal area for 3 consecutive days. One hour after the last administration, mice were intraperitoneally injected with 0.6% glacial acetic acid solution (0.1 mL / 10 g), and the number of writhing responses (abdominal contraction, hind limb extension, and body twisting) observed in each mouse within 15 minutes of injection was recorded.

[0076] (2) Needle prick pain test

[0077] The mechanical pain threshold of the hind paw in mice was determined using von Frey fibers to evaluate the analgesic effect of the patches described in Examples 1-8 on mechanical stinging. Kunming mice underwent surgery, with a 0.5 cm longitudinal incision made in the midline of the right hind paw, and the subcutaneous tissue was dissected and sutured. 24 h post-surgery, the paw withdrawal threshold in response to von Frey fiber stimulation significantly decreased. The corresponding patch (1.0 cm × 1.0 cm) was applied to the shaved area of ​​the right hind paw once daily for 3 consecutive days. A series of von Frey fibers with different bending forces (0.008 g–2.0 g) were used to vertically stimulate the center of the right hind paw, with each stimulation lasting 1–2 s. The bending force threshold for rapid paw withdrawal or licking behavior was recorded.

[0078] (3) Tumor compression pain test

[0079] The analgesic activity of the patches described in Examples 1-8 against tumor compression pain was evaluated using the S180 tumor compression pain mouse model. S180 cells were inoculated around the sciatic nerve in the right hind limb of mice to establish a tumor compression pain model. Starting on day 10 of modeling, the corresponding drugs were applied to the affected area once daily for 7 consecutive days. Twelve hours after the last administration, blood was collected from each group of mice, and serum PGE2 levels were detected using ELISA. The lumbar spinal cord was rapidly isolated using the area below the last rib as an anatomical landmark, and the expression of GFAP (a marker of astrocytes) and CD11b (a marker of microglia) in the dorsal horn of the mouse spinal cord was detected using immunohistochemistry.

[0080] Table 2 Analgesic effect of the patch of the present invention

[0081]

[0082] Experimental Example 3

[0083] Immunohistochemical staining of mouse spinal cord GFAP and CD11b (see [link to relevant documentation]) Figure 2 , Figure 3 As can be seen, in the mouse model of sciatica caused by tumor compression, both astrocytes and microglia in the spinal cord tissue were significantly activated, manifested by an increase in the number of positive cells, cell proliferation and hypertrophy, darker staining, and a significant increase in processes. After intervention with the patch of the present invention (Examples 1-8), the activation of GFAP and CD11b in each treatment group was reduced to varying degrees, the number of positive cells was significantly reduced, and the staining became lighter. Among them, the effects of groups 2, 3, and 7 were the most prominent, and the other groups of examples also had a certain inhibitory effect. The results show that the transdermal patch of the present invention, which uses toad venom and Aconitum carmichaelii as the core drug pair, supplemented with drugs that promote qi circulation, blood circulation, warm the interior, and dispel wind, can inhibit spinal cord astrocytes and microglia, thereby blocking the central sensitization pathway of pain and exerting an analgesic effect.

Claims

1. A traditional Chinese medicine composition containing toad venom and aconite root analgesic patch, comprising, by weight percentage: Toad venom 0.1-10%, Aconitum carmichaelii 5-98%, heat-clearing and swelling-reducing drugs 0-20%, qi-regulating and pain-relieving drugs 0-30%, blood-breaking and qi-regulating drugs 0-20%, blood-activating and pain-relieving drugs 0-30%, warming and cold-dispersing drugs 0-20%, wind-dispelling and cold-dispersing drugs 0-20%.

2. The traditional Chinese medicine composition according to claim 1, wherein: The toad venom is toad venom or wine-processed toad venom, and the aconite is raw aconite or processed aconite; The heat-clearing and swelling-reducing medicine is one or more of Paris polyphylla, Hibiscus leaf, dandelion, and Viola yedoensis. The qi-regulating and pain-relieving drugs are one or more of the following: Zanthoxylum nitidum, Nardostachys chinensis, Aucklandia lappa, and Corydalis yanhusuo. The blood-breaking and qi-regulating herbs are one or more of the following: Curcuma zedoaria, Sparganium stoloniferum, and Curcuma longa. The blood-activating and pain-relieving drugs are one or more of the following: frankincense, safflower, myrrh, chuanxiong, and notoginseng; The warming and dispelling cold medicines mentioned are one or more of the following: cinnamon, long pepper, galangal, cloves, and dried ginger; The wind-dispelling and cold-dispersing herbs are one or more of the following: Asarum, Ephedra sinica, Aconitum carmichaelii, Notopterygium incisum, and Angelica pubescens.

3. An analgesic preparation comprising the traditional Chinese medicine composition of claim 1 or 2 and pharmaceutically acceptable patch excipients.

4. The analgesic preparation according to claim 3, wherein: The drug-acceptable patch excipients include: Matrix material, moisturizer, transdermal absorption enhancer, backing material, anti-sticking material.

5. The analgesic preparation according to claim 3, wherein: The analgesic is in the form of a patch, which consists of, from top to bottom: a backing layer, a drug reservoir layer, and an anti-adhesion layer.

6. The analgesic preparation according to claim 4, wherein: The matrix material is one or more of polyvinyl alcohol, sodium carboxymethyl cellulose, glyceryl laurate, and hydroxypropyl methylcellulose; The humectant is one or more of glycerin, ethanol or ethylene glycol; The transdermal absorption enhancer is one or more of menthol, borneol, camphor, methyl salicylate, methanol, dimethyl sulfoxide, and azone.

7. The analgesic preparation according to claim 6, wherein: The transdermal absorption enhancer is prepared by mixing camphor, azone, and propylene glycol in a weight ratio of 1:1~2:1~3.

8. A method for preparing an analgesic agent according to any one of claims 3 to 7, comprising: The toad venom was pretreated to obtain pretreated toad venom for later use. Aconitum carmichaelii, heat-clearing and swelling-reducing drugs, qi-regulating and pain-relieving drugs, blood-breaking and qi-regulating drugs, blood-activating and pain-relieving drugs, warming and cold-dispelling drugs, and wind-dispelling and cold-dispelling drugs are pulverized separately, heated with ethanol and refluxed three times, filtered, the filtrates are combined, and concentrated under reduced pressure to obtain a fluid extract. The pretreated toad venom was incorporated into the fluid extract, the matrix material was fully swollen, and a humectant and transdermal absorption enhancer were added and stirred evenly. The above-mentioned active ingredients of traditional Chinese medicine are added to the matrix adhesive, stirred evenly, coated on the backing material, covered with an anti-sticking layer, and after drying and cutting, an analgesic preparation is obtained.

9. The preparation method according to claim 8, wherein: The toad venom pretreatment is selected from any of the following: Toad venom is extracted twice by reflux with 90% ethanol, the reflux liquids are combined and concentrated to dryness for later use; or toad venom is pulverized to obtain toad venom powder for later use.

10. The preparation method according to claim 8, wherein: The drying conditions are vacuum drying at 30~60℃ for 10~30 minutes.

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