External traditional Chinese medicine preparation formula for treating limb swelling and pain after venomous snake bites and preparation method of external traditional Chinese medicine preparation formula

Abstract

The invention discloses an external traditional Chinese medicine preparation formula for treating limb swelling and pain after venomous snake bites. The external traditional Chinese medicine preparation formula is characterized by comprising the following raw materials in parts by weight: 5-7 parts of paris polyphylla, 5-7 parts of Chinese lobelia, 2-4 parts of plantain herb, 2-4 parts of radix angelicae, 5-7 parts of lalang grass rhizome, 5-7 parts of hypericum japonicum, 4-6 parts of moutan bark, 4-6 parts of rheum officinale and 4-6 parts of golden cypress. The traditional Chinese medicine raw materials in scientific proportion are combined with a standard preparation process, through the synergistic effect of the composite efficacy module, the core problem that an existing external snake wound medicine is insufficient in pertinence and weak in synergism is solved, the application scene is further expanded, the use safety is improved, and the traditional Chinese medicine composition is worthy of popularization and application. Furthermore, the treatment effect on limb swelling and pain caused by bite of agkistrodon halys, agkistrodon acutus and trimeresurus trimeresurus can be remarkably improved.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine external preparations, specifically to a formulation and preparation method of a topical traditional Chinese medicine preparation for treating swelling and pain in the limbs after a venomous snake bite. Background Technology

[0002] Snakebites are a common acute traumatic condition in hilly and mountainous areas of southern my country. Among them, vipers, pit vipers, and bamboo pit vipers are highly venomous snakes with a wide distribution and high incidence of bites in my country. Their venom has a complex composition (containing hemolysins, neurotoxins, cytotoxins, etc.). After biting a human, it can quickly cause local swelling and severe pain in the limb. If not treated promptly and effectively, it may lead to local tissue congestion and necrosis, microcirculatory disorders, and in severe cases, even affect limb function, posing a significant threat to the patient's health and quality of life. Therefore, the development of topical treatment drugs for limb swelling and pain after bites from the above-mentioned specific venomous snakes is of great clinical urgency.

[0003] While some topical medications currently used clinically for limb swelling and pain following venomous snake bites have "heat-clearing and detoxifying" or "swelling-reducing and pain-relieving" effects, they still have many technical shortcomings in practical application and cannot meet the treatment needs for bites from vipers, pit vipers, and bamboo pit vipers.

[0004] Treatments for specific snake species lack specificity: Most existing topical medications are broad-spectrum snakebite treatments, failing to incorporate the pathological mechanisms of viper, pit viper, and bamboo pit viper venom, which are based on "local heat toxin accumulation and blood stasis." This results in limited relief of limb swelling and pain caused by bites from these snakes, often leading to "detoxification without swelling reduction" or "swelling reduction without pain relief," failing to simultaneously address the two core issues of heat toxin and blood stasis.

[0005] Weak synergistic effect of formulation: Most existing formulations have single ingredients or vague compatibility logic, relying only on 1-2 heat-clearing and detoxifying herbs (such as honeysuckle and dandelion), lacking a multi-effect synergistic design of "heat-clearing and detoxifying - swelling-reducing and pain-promoting diuresis and detoxification - cooling blood and dispersing blood stasis", and failing to form a complete chain of action against the local pathological reaction caused by snake venom, resulting in slow drug efficacy, long swelling and pain relief period, and prolonged patient suffering.

[0006] In summary, given the specific clinical need for limb swelling and pain after bites from vipers, pit vipers, and bamboo pit vipers, the current topical treatments lack specificity and synergy. Developing a topical traditional Chinese medicine preparation that is scientifically formulated, has strong synergistic effects, is easy to prepare, has high safety, and can effectively address limb swelling and pain after bites from these snake species has become an urgent technical problem to be solved in this field. Summary of the Invention

[0007] The purpose of this invention is to address the technical shortcomings of existing topical snakebite treatment drugs, such as slow onset of action and weak synergistic effect. This invention provides a topical traditional Chinese medicine preparation for treating limb swelling and pain after venomous snake bites, which has a scientific formula, strong synergistic effect, rapid onset of action, high safety, and simple preparation method.

[0008] To achieve the above-mentioned technical objectives and effects, the present invention is implemented through the following technical solution:

[0009] A topical traditional Chinese medicine preparation for treating swelling and pain in the limbs after a venomous snake bite is composed of the following ingredients in parts by weight: 5-7 parts of Paris polyphylla, 5-7 parts of Lobelia chinensis, 2-4 parts of Plantago asiatica, 2-4 parts of Angelica dahurica, 5-7 parts of Imperata cylindrica, 5-7 parts of Clematis chinensis, 4-6 parts of Paeonia suffruticosa, 4-6 parts of Rheum palmatum, and 4-6 parts of Phellodendron chinense.

[0010] A method for preparing a topical traditional Chinese medicine preparation for treating swelling and pain in the limbs after a venomous snake bite, characterized by the following steps:

[0011] S1. Selection of medicinal materials: Select nine raw medicinal materials, namely Paris polyphylla, Lobelia chinensis, Plantago asiatica, Angelica dahurica, Imperata cylindrica, Clematis chinensis, Paeonia suffruticosa, Rheum palmatum, and Phellodendron chinense, for later use.

[0012] S2. Crushing process: The nine raw medicinal materials are crushed. During the crushing process, the particle size of the crushed medicinal materials is controlled by a 5mm sieve to ensure that all crushed medicinal materials can pass through the 5mm sieve to obtain coarse powder.

[0013] S3. Sterilization and drying: The crude medicinal powder obtained in S2 is placed in a humid heat environment at 105℃ (sterilized by high-temperature steam) and sterilized for 30 minutes. After sterilization, it is dried at 105℃ for 120-240 minutes to obtain sterilized and dried crude medicinal powder.

[0014] S4. Crushing and sieving: The coarse powder of the medicinal materials after sterilization and drying in S3 is crushed and then sieved through a 100-mesh sieve. The fine powder of the medicinal materials that passes through the 100-mesh sieve is collected.

[0015] S5. Blending process: The fine powder of medicinal materials collected in S4 is blended together to obtain intermediate products;

[0016] S6. Sampling of intermediate products: Sampling of the intermediate products obtained in S5;

[0017] S7. Repackaging: After the intermediate product passes the inspection, it is repackaged to obtain a topical Chinese medicine preparation for treating swelling and pain in the limbs after a venomous snake bite.

[0018] Preferably, this topical Chinese medicine preparation is used in the preparation of a medicine for treating limb swelling and pain after bites from vipers, five-step snakes, and bamboo pit vipers.

[0019] Application of topical Chinese medicine preparations for treating swelling and pain in limbs after snake bites: Topical Chinese medicine preparations are used to treat swelling and pain in limbs accompanied by minor skin damage after snake bites. When using, mix the fine powder of the medicinal materials with 0.9% sodium chloride injection at a weight ratio of 3:1 to form a paste, apply it to the swollen and damaged areas, and cover it with sterile gauze after application.

[0020] Preferably, the weight ratio of Paris polyphylla to Lobelia chinensis is 1:1 (6 parts: 6 parts), and the weight ratio of Plantago asiatica to Imperata cylindrica is 1:2 (3 parts: 6 parts).

[0021] Preferably, the raw materials also include 2-4 parts of Ligusticum chuanxiong and 3-5 parts of Lonicera japonica.

[0022] Preferably, the weight ratio of Ligusticum chuanxiong to Paeonia suffruticosa in the original formula is 1:1.7 (3 parts: 5 parts).

[0023] Preferably, the total weight ratio of honeysuckle to the original formula of Paris polyphylla and Lobelia chinensis is 1:3 (4 parts: (6 parts + 6 parts)).

[0024] Preferably, the preparation steps follow the preparation method of external Chinese medicine preparations for treating limb swelling and pain after snake bites. In the S2 crushing process, Chuanxiong, honeysuckle and the original nine medicinal materials are crushed together. The S3 sterilization and drying, S4 pulverization and sieving, and S5 total mixing are all carried out simultaneously with the original nine medicinal materials. In the total mixing, Chuanxiong fine powder and Moutan bark fine powder are first premixed according to the "equal amount incremental method", then honeysuckle fine powder, Paris polyphylla fine powder and Lobelia chinensis fine powder are premixed, and finally combined with the fine powders of the remaining medicinal materials and mixed together.

[0025] The beneficial effects of this invention are:

[0026] This invention combines scientifically proportioned Chinese herbal raw materials with standardized preparation processes. Through the synergistic effect of compound efficacy modules, it not only solves the core problems of existing external snakebite medications—"insufficient targeting and weak synergy"—but also further expands applicable scenarios and improves safety, thereby significantly improving the treatment effect on limb swelling and pain after bites from vipers, pit vipers, and bamboo pit vipers. Specifically, Paris polyphylla and Lobelia chinensis serve as core detoxifying herbs, with a 1:1 weight ratio ensuring potent heat-clearing, detoxifying, swelling-reducing, and pain-relieving effects. They synergistically address the core cause of "heat toxin accumulation" in snake venom, quickly relieving severe pain. Paeonia suffruticosa and rhubarb cool the blood. The formula, combined with the preferred blend of Ligusticum chuanxiong (in a 1:1.7 ratio with Paeonia suffruticosa), enhances the effects of clearing the meridians and dispersing blood stasis, simultaneously addressing limb swelling caused by "qi and blood stasis," and avoiding the phenomenon of "detoxification without reducing swelling" and "reducing swelling without relieving pain." Plantain and Imperata cylindrica, in a 1:2 ratio, work synergistically to promote diuresis and detoxification, accelerating the excretion of snake venom metabolites and shortening the swelling and pain relief period. Angelica dahurica assists in reducing swelling and relieving pain, while Phellodendron amurense enhances its heat-clearing and dampness-drying effects, reducing local inflammatory reactions. The preferred blend of Lonicera japonica (in a 1:3 ratio with Paris polyphylla and Lobelia chinensis) further enhances its heat-clearing and detoxifying activity, synergistically strengthening the anti-toxic effect with the core medicinal materials.

[0027] Meanwhile, the preparation process employs 105℃ moist heat sterilization and 100-mesh sieving to control particle fineness, ensuring the sterility and safety of the medicinal materials while facilitating the release of active ingredients. The "equal-volume incremental method" in the total mixing stage ensures uniform mixing of all components, avoiding uneven local efficacy. The application method, combined with 0.9% sodium chloride injection at a 3:1 ratio, minimizes irritation and is suitable for minor skin abrasions, reducing the risk of secondary damage and expanding the scope of application. The preparation process requires no complex equipment, is simple and controllable, and the optimized formula does not require additional process steps for the addition of medicinal materials, facilitating clinical promotion and large-scale production. Ultimately, it achieves a multi-effect combination of "detoxification, swelling reduction, pain relief, toxic elimination, and repair," fully meeting the urgent clinical needs for emergency treatment of snake bites. Detailed Implementation

[0028] To more clearly illustrate the technical solutions of the embodiments of the present invention, the present invention will be described in detail below with reference to the embodiments.

[0029] A topical traditional Chinese medicine preparation for treating swelling and pain in the limbs after a venomous snake bite is composed of the following ingredients in parts by weight: 5-7 parts of Paris polyphylla, 5-7 parts of Lobelia chinensis, 2-4 parts of Plantago asiatica, 2-4 parts of Angelica dahurica, 5-7 parts of Imperata cylindrica, 5-7 parts of Clematis chinensis, 4-6 parts of Paeonia suffruticosa, 4-6 parts of Rheum palmatum, and 4-6 parts of Phellodendron chinense.

[0030] A method for preparing a topical traditional Chinese medicine preparation for treating swelling and pain in the limbs after a venomous snake bite, characterized by the following steps:

[0031] S1. Selection of medicinal materials: Select nine raw medicinal materials, namely Paris polyphylla, Lobelia chinensis, Plantago asiatica, Angelica dahurica, Imperata cylindrica, Clematis chinensis, Paeonia suffruticosa, Rheum palmatum, and Phellodendron chinense, for later use.

[0032] S2. Crushing process: The nine raw medicinal materials are crushed. During the crushing process, the particle size of the crushed medicinal materials is controlled by a 5mm sieve to ensure that all crushed medicinal materials can pass through the 5mm sieve to obtain coarse powder.

[0033] S3. Sterilization and drying: The crude medicinal powder obtained in S2 is placed in a humid heat environment at 105℃ (sterilized by high-temperature steam) and sterilized for 30 minutes. After sterilization, it is dried at 105℃ for 120-240 minutes to obtain sterilized and dried crude medicinal powder.

[0034] Specifically, the coarse powder of medicinal materials collected by S2 is evenly spread in the tray of the moist heat drying and sterilization equipment (the spreading thickness does not exceed 3cm to ensure uniform heating). After turning off the equipment, the parameters are set as follows: first, the coarse powder of medicinal materials is sterilized in a moist heat environment at 105℃ for 30 minutes; after sterilization, the equipment temperature is maintained at 105℃, and the coarse powder of medicinal materials is dried for a period of 120-240 minutes (adjusted according to the initial moisture content of the coarse powder of medicinal materials; if the initial moisture content is high, the drying time is extended, and if the initial moisture content is low, the drying time is shortened). During the drying process, the moisture content of the coarse powder of medicinal materials is sampled and tested periodically until the moisture content of the coarse powder of medicinal materials is ≤9% (mass fraction). Then, the drying is stopped, the dried and sterilized coarse powder of medicinal materials is taken out, cooled to room temperature, and stored for later use.

[0035] S4. Crushing and sieving: The coarse powder of the medicinal materials after sterilization and drying in S3 is crushed and then sieved through a 100-mesh sieve. The fine powder of the medicinal materials that passes through the 100-mesh sieve is collected.

[0036] Specifically, the coarse powder of the medicinal materials after cooling in S3 is fed into an ultrafine pulverizing device for pulverization. After pulverization, the powder is transferred to a vibrating sieve and sieved using a 100-mesh standard pharmacopoeia sieve. The fine powder that passes through the 100-mesh sieve is collected. The coarse powder remaining on the sieve is returned to the ultrafine pulverizing device for pulverization again. The pulverization-sieving operation is repeated until all the powder can pass through the 100-mesh sieve, ensuring that the particle size of the finally collected fine powder meets the 100-mesh standard and is ready for use.

[0037] S5. Blending process: The fine powder of medicinal materials collected in S4 is blended together to obtain intermediate products;

[0038] Specifically, all the 100-mesh fine powder of medicinal materials collected in S4 is put into the pharmaceutical mixer. After turning off the mixer, the mixing parameters are set as follows: mixing speed is 15-20 r / min, and mixing time is 15-20 min. During the mixing process, a small amount of fine powder of medicinal materials is taken from different sampling points of the mixer (including the top, middle, bottom and outlet of the mixer) every 5 min. The mixing uniformity of the samples is verified by the "equal amount addition method" until the mixing uniformity RSD (relative standard deviation) of the samples at all sampling points is ≤3%. The fine powder of medicinal materials is judged to be mixed uniformly, the mixing is stopped, and the intermediate product is obtained for later use.

[0039] S6. Sampling of intermediate products: Sampling of the intermediate products obtained in S5;

[0040] Specifically, intermediate product sampling and testing: In accordance with the sampling requirements for intermediate products of topical preparations, a sufficient amount of sample is extracted from the intermediate product obtained in S5, and the following items are tested on the sample: ① Particle size test: The sieving method is used for testing, and more than 95% of the sample is required to pass through a 100-mesh sieve; ② Moisture test: The drying method is used for testing, and the moisture content of the sample is required to be ≤9%; After all the test items are qualified, proceed to the next step; If there are any unqualified items in the test items, it is necessary to return to step (5) for total mixing or step (4) for pulverization and sieving until the intermediate product is qualified.

[0041] S7. Repackaging: After the intermediate product passes inspection, it is repackaged to obtain a topical traditional Chinese medicine preparation for treating swelling and pain in the limbs after snake bites.

[0042] Specifically, the intermediate product (fine powder of medicinal materials) that has passed the S6 test is transferred into an automated pharmaceutical dispensing equipment. The dispensing parameters are set as follows: quantitative dispensing is performed according to the clinical single-use dosage (5-10g per bag / bottle, the specific dispensing amount can be adjusted according to market demand and clinical usage habits); the dispensing containers are sealed containers that meet pharmaceutical standards (such as aluminum-plastic composite film bags, pharmaceutical high-density polyethylene bottles). After dispensing, the containers are immediately sealed (aluminum-plastic composite film bags are sealed by heat pressing, and pharmaceutical plastic bottles are sealed with screw caps and sealing gaskets). After sealing, a label is affixed to the surface of the container (the label indicates the product name, specifications, batch number, production date, expiration date, ingredients, usage and dosage, storage conditions, etc.), thus obtaining the finished external Chinese medicine preparation for treating limb swelling and pain after snake bites.

[0043] This topical traditional Chinese medicine preparation is used in the preparation of a medicine for treating limb swelling and pain after bites from vipers, pit vipers, and bamboo pit vipers. It is worth noting that the core mechanism of action of this invention targets the common pathological characteristics of "heat toxin accumulation, blood stasis, and slow venom metabolism" after snake bites, exerting its therapeutic effect through the synergistic effects of "clearing heat and detoxifying, reducing swelling and relieving pain, promoting blood circulation and unblocking collaterals, and promoting diuresis and detoxification." Vipers, pit vipers, and bamboo pit vipers are typical application targets of this invention, verified through experiments. Their venom components (mainly hemolysin and cytotoxin) and post-bite pathological manifestations are consistent with those of other common venomous snakes such as pit vipers and cobras. Therefore, the scope of application includes, but is not limited to, the above three types of snakes.

[0044] External application of traditional Chinese medicine preparations is used to treat swelling and pain in limbs with minor skin damage after snake bites. When using, mix the fine powder of the medicinal material with 0.9% sodium chloride injection at a weight ratio of 3:1 to form a paste, apply it to the swollen and damaged areas, and cover it with sterile gauze after application.

[0045] The weight ratio of Paris polyphylla to Lobelia chinensis was 1:1 (6 parts: 6 parts), and the weight ratio of Plantago asiatica to Imperata cylindrica was 1:2 (3 parts: 6 parts).

[0046] The raw materials also include 2-4 parts of Ligusticum chuanxiong and 3-5 parts of Lonicera japonica.

[0047] It is worth noting that in the original nine medicinal herbs, Paris polyphylla and Lobelia chinensis were the principal herbs, mainly used to clear heat and detoxify, reduce swelling and relieve pain; Plantago asiatica and Imperata cylindrica were the assistant herbs, mainly used to promote diuresis and detoxify; Angelica dahurica, Gentiana scabra, and Paeonia suffruticosa were the adjuvant herbs, mainly used to dispel wind, invigorate blood, cool blood and disperse blood stasis; Rheum palmatum and Phellodendron chinense were the guiding herbs, mainly used to clear heat and dry dampness; the newly added Ligusticum chuanxiong enters the liver, gallbladder and pericardium meridians, can invigorate blood and promote qi circulation, dispel wind and unblock collaterals, and its ligustrazine can improve local microcirculation disorders after snake bites, enhance the blood-cooling and blood-dispersing effects of Paeonia suffruticosa, and accelerate the excretion of venom metabolites; Lonicera japonica It enters the lung, heart, and stomach meridians, and can clear heat and detoxify, and disperse wind-heat. The chlorogenic acid and luteolin it contains can enhance the heat-clearing and detoxifying effects of Paris polyphylla and Lobelia chinensis, while inhibiting secondary bacterial infection at the bite site (Staphylococcus and Streptococcus easily grow in the mouth and wound of venomous snakes), making up for the lack of "anti-secondary infection" effect of the original formula. Together with the original nine medicinal materials, they form a four-dimensional synergistic system of "clearing heat and detoxifying, promoting diuresis and detoxification, promoting blood circulation and unblocking collaterals, and anti-infection and wound protection", which specifically solves the four core pathological problems of "toxicity, swelling, bruising and infection" after venomous snake bites.

[0048] Using the same animal model of the five-step snake venom as the formulation of claim 1 (40 healthy rabbits, subcutaneously injected with 0.2 mL of 0.5 mg / mL five-step snake venom in the right hind limb), the animals were randomly divided into 3 groups (the formulation group of claim 1, the new composition group of claim 2, and the blank control group), with 10 animals in each group. The administration method was "mixing the fine powder of the medicinal material with 0.9% sodium chloride injection to form a paste and applying it topically, 3 times a day". The key indicators were recorded as follows:

[0049] Group Swelling subsidence time (h) Pain relief time (h) Secondary infection rate (%) Effectiveness (%) Claim 1 Formulation group 28±3.2 12±2.1 15 100 Claim 6 adds a new composition group 22±2.8 9±1.8 0 100 Blank control group 96±6.5 48±5.2 80 20

[0050] Experimental results showed that after adding Ligusticum chuanxiong and Lonicera japonica, the swelling reduction time of the preparation was shortened by 21.4% and the pain relief time was shortened by 25% compared with the original formula, and secondary infection was eliminated. This confirms that the "blood-activating and meridian-clearing" effect of Ligusticum chuanxiong can accelerate the discharge of local toxins and blood stasis, and the "heat-clearing and detoxifying" effect of Lonicera japonica can block the infection pathway. The combined effect of the two with the original formula is significantly better than the original formula alone, and there are no adverse reactions such as skin irritation or allergies (skin irritation test showed that there was no redness, swelling, exudation, or hair loss at the application site on rabbits).

[0051] The weight ratio of Ligusticum chuanxiong to Paeonia suffruticosa in the original formula was 1:1.7 (3 parts: 5 parts). This ratio was determined through a "gradient ratio verification experiment": three groups of preparations were prepared according to the ratios of "Ligusticum chuanxiong: Paeonia suffruticosa" = "1:1", "1:1.7", and "1:2.5". The microcirculation improvement effect on snakebite model animals (local blood flow was detected by laser Doppler flowmeter) showed that at the "1:1.7" ratio, the blood flow at the bite site of the animals increased by 42% compared with the baseline value after the bite, which was better than the "1:1" ratio (28% increase) and the "1:2.5" ratio (33% increase). This proves that this ratio can maximize the synergistic effect of "blood-activating and blood-cooling" of Ligusticum chuanxiong and Paeonia suffruticosa, and avoid excessive local vasodilation caused by excessive Ligusticum chuanxiong or slight impact on coagulation function caused by excessive Paeonia suffruticosa.

[0052] The total weight ratio of honeysuckle to the original formula of Paris polyphylla and Lobelia chinensis is 1:3 (4 parts: (6 parts + 6 parts)). This ratio was determined through an "antibacterial effect verification experiment": using the paper disc diffusion method, the diameter of the inhibition zone against Staphylococcus aureus (a common pathogen in snake bites) was tested for different proportions of honeysuckle. The results showed that the diameter of the inhibition zone at the "1:3" ratio was 18.2 mm, which was better than the "1:4" ratio (15.5 mm) and the "1:2" ratio (16.8 mm), and did not affect the core efficacy of Paris polyphylla and Lobelia chinensis in reducing swelling and relieving pain (the swelling reduction time was not prolonged). This proves that this ratio can maintain the core therapeutic effect of the original formula while strengthening the anti-cold effect, and avoid the imbalance of the efficacy of the medicinal materials.

[0053] The preparation steps follow the method for preparing topical Chinese medicine preparations for treating swelling and pain in the limbs after snake bites. In the S2 crushing process, Ligusticum chuanxiong, Lonicera japonica and the original nine medicinal materials are crushed together. The S3 sterilization and drying, S4 pulverization and sieving, and S5 total mixing processes are all carried out simultaneously with the original nine medicinal materials. In the total mixing process, the fine powder of Ligusticum chuanxiong and the fine powder of Paeonia suffruticosa are premixed according to the "equal amount incremental method". Then the fine powder of Lonicera japonica, Paris polyphylla, and Lobelia chinensis are premixed. Finally, the fine powders of the remaining medicinal materials are combined and mixed together.

[0054] Example of a topical traditional Chinese medicine preparation for treating swelling and pain in the limbs after a venomous snake bite.

[0055] I. Basic Experimental Information

[0056] 1. Experimental Model Construction

[0057] Sixty healthy rabbits (weighing 2.0-2.5 kg, half male and half female) were selected and fed acclimatized for 3 days. A limb swelling and pain model caused by venomous snake bites was established: 0.2 mL of 0.5 mg / mL five-step snake venom solution (five-step snake venom purchased from Kunming Institute of Zoology, Chinese Academy of Sciences, and qualified for purity testing) was injected subcutaneously into the lateral side of the right hind leg of each rabbit. Two hours after injection, obvious redness and swelling (swelling area diameter ≥3 cm) were observed at the injection site, and the rabbits showed limited limb movement (lameness). The model was then determined to be successfully established.

[0058] 2. Definition of detection indicators

[0059] Swelling subsidence time: From the first dose of medication until the swelling at the injection site shrinks to ≤0.5cm and there is no tenderness upon palpation;

[0060] Pain relief time: The pain rating scale (0 points: no pain response; 1 point: leg retraction upon slight touch; 2 points: active avoidance of touch; 3 points: limb tremors while resting; 4 points: persistent agitation and biting of the affected limb) was used to measure the time from the first dose of medication until the score stabilized at ≤1 point.

[0061] Secondary infection rate: 72 hours after administration, observe whether there is exudation, suppuration or skin ulceration at the injection site, and calculate the proportion of infected rabbits in the total number of rabbits in the group;

[0062] Efficacy rate: The percentage of rabbits in the group that met the criteria of "swelling subsides + pain relief + no secondary infection";

[0063] Skin irritation: During the course of medication, observe the application site daily for redness, swelling, oozing, or hair loss. If no such reactions occur throughout the course of treatment, it is considered "non-irritating". Specific Implementation

[0064] Example 1 (Basic formulation, corresponding to claims 1 and 5)

[0065] 1.1 Formulation Composition (parts by weight)

[0066] Paris polyphylla 6 parts, Lobelia chinensis 6 parts (Paris polyphylla: Lobelia chinensis = 1:1), Plantago asiatica 3 parts, Imperata cylindrica 6 parts (Plantago asiatica: Imperata cylindrica = 1:2), Clematis chinensis 6 parts, Paeonia suffruticosa 5 parts, Rheum palmatum 5 parts, Phellodendron chinense 5 parts.

[0067] 1.2 Preparation method (corresponding to claim 2)

[0068] S1: Select the above nine medicinal materials;

[0069] S2: Put the nine medicinal herbs into the universal crusher, control the particle size through a 5mm mesh screen, and collect the coarse powder of the herbs after crushing.

[0070] S3: Spread the coarse powder evenly on the tray of the moist heat sterilization drying oven (spreading thickness 2cm), sterilize at 105℃ for 30min, and continue drying at 105℃ for 180min. The moisture content is tested to be 6.2% (meeting the requirement of ≤9%).

[0071] S4: Put the dry coarse powder into the ultra-fine pulverizer, pulverize it and pass it through a 100-mesh sieve. The remaining coarse powder is pulverized again and finally the 100-mesh fine powder is collected.

[0072] S5: Add the fine powder into the three-dimensional motion mixer, rotate at 18 r / min, mix for 18 min, take a sample to test the mixing uniformity RSD=2.1% (≤3%), and obtain the intermediate product;

[0073] S6: Take samples of intermediate products and test particle size (98% passing through a 100-mesh sieve) and moisture (6.2%) to determine compliance (the aforementioned tests must be carried out on the premise that the raw materials selected in step S1 have been inspected in advance (meeting the standards of the current edition of the Chinese Pharmacopoeia, Part I, and the content of key components meets the standards)).

[0074] S7: Packed in pharmaceutical aluminum-plastic composite film bags, 8g per bag (single dose), and heat-sealed (125℃, 4s) to obtain the finished product.

[0075] 1.3 Method of administration

[0076] For the scenario of "minor skin damage after snake bite" (corresponding to claim 4): Take 8g of the finished fine powder and mix it with 0.9% sodium chloride injection at a weight ratio of 3:1 to form a paste. Apply the paste evenly to the swollen and damaged area of ​​the right hind limb of the rabbit (damaged area ≤0.3cm²), with a thickness of 2mm. Cover with sterile gauze after application, and repeat 3 times a day.

[0077] Example 2 (adding Ligusticum chuanxiong and Lonicera japonica, corresponding to claims 6, 7, 8, and 9)

[0078] 2.1 Formulation composition (parts by weight)

[0079] In the basic formula of Example 1, 3 parts of Ligusticum chuanxiong and 4 parts of Lonicera japonica were added, wherein:

[0080] Chuanxiong (Ligusticum striatum): Mudanpi (Paeonia suffruticosa) = 3 parts: 5 parts = 1:1.7;

[0081] Honeysuckle : (Paris polyphylla + Lobelia chinensis) = 4 parts : (6 parts + 6 parts) = 1 : 3.

[0082] 2.2 Preparation method (corresponding to claim 9)

[0083] S1-S2: Select and put the chuanxiong (containing ≥0.8% chuanxiong alkaloids) and honeysuckle (containing ≥1.5% chlorogenic acid) together with the original nine medicinal materials into a crusher, crush them through a 5mm aperture screen, and collect the mixed coarse powder;

[0084] S3: Same as Example 1, but with a moisture content of 6.0% after drying;

[0085] S4: Same as in Example 1, collect 100-mesh fine powder;

[0086] S5: When mixing the total mixture, first premix using the "equal increment method": ① Mix 3g of fine powder of Ligusticum chuanxiong with 5g of fine powder of Paeonia suffruticosa for 5 minutes; ② Mix 4g of fine powder of Lonicera japonica with 6g of fine powder of Paris polyphylla and 6g of fine powder of Lobelia chinensis for 5 minutes; Add the two premixed powders together with the remaining fine powders of medicinal materials (3g of Plantago asiatica, 6g of Imperata cylindrica, 6g of Gynostemma pentaphyllum, 5g of Rheum palmatum, and 5g of Phellodendron chinense) into a three-dimensional motion mixer, rotate at 18 r / min, mix for 18 minutes, and check the mixing uniformity RSD=1.8%;

[0087] S6-S7: Same as Example 1, intermediate products are repackaged after passing inspection.

[0088] 2.3 Method of administration

[0089] Same as Example 1.

[0090] Example 3 (Basic formulation variables, corresponding to the weight range of claim 1)

[0091] 3.1 Formulation composition (parts by weight)

[0092] 5 parts of Paris polyphylla, 7 parts of Lobelia chinensis, 2 parts of Plantago asiatica, 4 parts of Angelica dahurica, 5 parts of Imperata cylindrica, 7 parts of Clematis chinensis, 4 parts of Paeonia suffruticosa, 6 parts of Rheum palmatum, and 4 parts of Phellodendron chinense (all within the range of "5-7 parts", "2-4 parts", and "4-6 parts" in claim 1).

[0093] 3.2 Preparation method

[0094] Same as Example 1 (drying time 120 min, moisture content 7.5%; total mixing time 15 min, RSD=2.8%).

[0095] 3.3 Method of administration

[0096] Same as Example 1.

[0097] III. Proportional Settings

[0098] Comparative Example 1 (lacking the main ingredient, Paris polyphylla)

[0099] Formula: Remove Paris polyphylla from Example 1, and keep the dosage of other medicinal materials unchanged (6 parts Lobelia chinensis, 3 parts Plantago asiatica, 6 parts Imperata cylindrica, etc.); the preparation method and administration method are the same as in Example 1.

[0100] Comparative Example 2 (Deviating from the preferred ratio)

[0101] Formula: 10 parts of Paris polyphylla, 3 parts of Lobelia chinensis, 5 parts of Plantago asiatica, and 3 parts of Imperata cylindrica (deviating from the range of "5-7 parts" and "2-4 parts" in claim 1, and Paris polyphylla: Lobelia chinensis = 10:3 ≠ 1:1, Plantago asiatica: Imperata cylindrica = 5:3 ≠ 1:2); the preparation method and administration method are the same as in Example 1.

[0102] Comparative Example 3 (Traditional Snakebite Topical Formula)

[0103] Formula: 3 parts realgar, 5 parts alum, 2 parts borneol, 6 parts honeysuckle, 6 parts dandelion, 6 parts violet (a commonly used traditional formula in clinical practice); Preparation method: only pulverized through an 80-mesh sieve, without 105℃ moist heat sterilization; Administration method: same as in Example 1.

[0104] Comparative Example 4 (Basic Formula without Ligusticum chuanxiong and Lonicera japonica)

[0105] The formula and preparation method are the same as in Example 1, except that the method of administration is "fine powder + distilled water to make a paste" (instead of 0.9% sodium chloride injection).

[0106] Blank control group

[0107] An equal amount of 0.9% sodium chloride injection solution was applied only to the right hind limb of the model rabbit three times a day, without using any traditional Chinese medicine preparations.

[0108] IV. Comparison of Experimental Data and Analysis of Results

[0109] 1. Comparison table of efficacy data for each group

[0110] Group Number of rabbits in the experiment (none) Swelling subsidence time (h) Pain relief time (h) Secondary infection rate (%) Effectiveness (%) Skin irritation Example 1 8 28.5±3.1 12.2±2.0 12.5（1 / 8） 100（8 / 8） Non-irritating Example 2 8 21.8±2.7 8.9±1.7 0（0 / 8） 100（8 / 8） Non-irritating Example 3 8 31.2±3.4 14.5±2.2 12.5（1 / 8） 100（8 / 8） Non-irritating Comparative Example 1 8 55.7±4.6 27.8±3.4 37.5（3 / 8） 75（6 / 8） Non-irritating Comparative Example 2 8 44.9±4.1 21.6±3.0 25（2 / 8） 87.5（7 / 8） Non-irritating Comparative Example 3 8 61.8±5.2 31.9±4.0 50（4 / 8） 62.5（5 / 8） Mild irritation (redness and swelling appeared in 2 animals) Comparative Example 4 8 29.1±3.2 12.8±2.1 25（2 / 8） 87.5（7 / 8） Non-irritating Blank control group 8 95.6±6.4 47.8±5.1 87.5（7 / 8） 12.5（1 / 8） -

[0111] Results Analysis

[0112] (1) Validation of the effectiveness of the basic formulation (Examples 1 and 3 vs. Comparative Examples 1 and 2 and the blank group)

[0113] The swelling subsidence time (28.5h) and pain relief time (12.2h) of Example 1 (preferred ratio) were significantly shorter than those of Comparative Example 1 (lacking Paris polyphylla, 55.7h / 27.8h), proving that Paris polyphylla is the core heat-clearing and detoxifying component, and its absence significantly reduces the efficacy.

[0114] The efficacy rate of Example 1 (100%) was higher than that of Comparative Example 2 (deviated from the preferred ratio, 87.5%), and the swelling subsided in 14.4 hours, indicating that the preferred ratio of "Paris polyphylla: Lobelia chinensis = 1:1, Plantago asiatica: Imperata cylindrica = 1:2" in claim 5 can maximize the synergistic effect of the medicinal materials.

[0115] The efficacy rates of Examples 1 and 3 were both 100%, significantly higher than that of the blank group (12.5%), verifying that the weight ranges of "5-7 parts", "2-4 parts", and "4-6 parts" in claim 1 are scientifically reasonable and can stably exert the drug's efficacy.

[0116] (2) Synergistic effect of adding Ligusticum chuanxiong + Lonicera japonica (Example 2 vs Example 1, Comparative Example 4)

[0117] The swelling subsidence time (21.8h) in Example 2 was shortened by 23.5% compared to Example 1, the pain relief time (8.9h) was shortened by 27.0%, and the secondary infection rate decreased from 12.5% ​​to 0, which confirms that the blood-activating and meridian-clearing effects of Ligusticum chuanxiong can accelerate the excretion of toxins and blood stasis, and the antibacterial effect of Lonicera japonica can block the infection pathway (corresponding to the formulation design of claims 6, 7, and 8).

[0118] The efficacy of Example 2 was superior to that of Comparative Example 4 (without Ligusticum chuanxiong and honeysuckle, and mixed with distilled water), further demonstrating that the combination of the added medicinal material and "mixed with 0.9% sodium chloride injection" can enhance the therapeutic effect.

[0119] (3) Advantages of the present invention compared with traditional formulations (Example 1 vs. Comparative Example 3)

[0120] The swelling subsidence time of Example 1 was 53.9% shorter than that of Comparative Example 3 (traditional formula), and the efficacy rate (100%) was significantly higher than that of the traditional formula (62.5%). Moreover, there was no skin irritation. Comparative Example 3, on the other hand, was not sterilized and contained realgar, which posed a risk of microbial contamination (secondary infection rate of 50%) and skin irritation. This proves that the present invention is superior to the traditional formula in terms of efficacy, safety and process rationality.

[0121] In the description of this specification, references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0122] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. A formula of external use of traditional Chinese medicine for treating swollen and painful limbs after snake bite, characterized in that: It is composed of the following raw materials by weight fraction: 5-7 parts of rhizoma paridis, 5-7 parts of lobelia, 2-4 parts of plantago, 2-4 parts of angelica, 5-7 parts of imperata, 5-7 parts of ground ivy, 4-6 parts of cortex moutan, 4-6 parts of rhubarb, and 4-6 parts of phellodendron. ​ 2. The preparation method of the external use traditional Chinese medicine preparation for treating the swollen and painful limbs after snake bites according to claim 1, characterized in that: It comprises the following steps: S1, selecting medicinal materials: selecting rhizoma paridis, lobelia, plantago, angelica, imperata, ground ivy, cortex moutan, rhubarb, and phellodendron as nine kinds of raw medicinal materials for standby; S2, crushing treatment: crushing the nine kinds of raw medicinal materials, and controlling the particle size of the crushed medicinal material particles by a 5mm mesh screen during the crushing process to ensure that the crushed medicinal material particles can all pass through the 5mm mesh screen, thereby obtaining medicinal material coarse powder; S3, sterilization and drying: placing the medicinal material coarse powder obtained in S2 in a humid heat environment at 105°C, first performing 30min of sterilization treatment, and then continuing to perform 120-240min of drying treatment at 105°C, thereby obtaining sterilized and dried medicinal material coarse powder; S4, crushing and sieving: crushing the sterilized and dried medicinal material coarse powder obtained in S3, and then sieving the crushed material through a 100 mesh screen to collect medicinal material fine powder that passes through the 100 mesh screen; S5, total mixing treatment: total mixing the medicinal material fine powder collected in S4 to obtain an intermediate product; S6, sampling of the intermediate product: sampling the intermediate product obtained in S5; S7, packaging: after the intermediate product is detected to be qualified, packaging it, thereby obtaining the external use traditional Chinese medicine preparation for treating limb swelling and pain after snake bite.

3. The external use of traditional Chinese medicine preparation for treating the limb swelling and pain after snake bite according to claim 2, characterized in that, The external use traditional Chinese medicine preparation is used for treating limb swelling and pain after snake bite.

4. The use of the external preparation of traditional Chinese medicine for treating the swollen and painful limbs after snake bites according to claim 3, characterized in that, The external use traditional Chinese medicine preparation is used for treating limb swelling and pain after snake bite.

5. The external use of traditional Chinese medicine preparation formula for treating the pain and swelling of the lower limbs after snake bites according to claim 1, characterized in that, The weight ratio of rhizoma paridis to lobelia in the raw medicinal materials is 1:1, and the weight ratio of plantago to imperata is 1:

2.

6. The external use traditional Chinese medicine preparation formula for treating the swollen and painful limbs after snake bite injury according to claim 1 or 5, characterized in that: The raw medicinal materials further comprise 2-4 parts of ligusticum and 3-5 parts of honeysuckle.

7. The topical traditional Chinese medicine preparation formula for treating limb swelling and pain after a venomous snake bite as described in claim 6, characterized in that: The weight ratio of ligusticum to cortex moutan in the original formula is 1:1.

7.

8. The external use traditional Chinese medicine preparation for treating the swollen and painful limbs after snake bite according to claim 6, characterized in that: The weight ratio of honeysuckle to the total weight of rhizoma paridis and lobelia in the original formula is 1:

3.

9. The preparation method of the external use traditional Chinese medicine preparation for treating the swollen and painful limbs after snake bites according to claim 6, characterized in that, The preparation steps of claim 2 are followed, and in the crushing treatment of S2, ligusticum and honeysuckle are crushed together with the original nine kinds of medicinal materials, and S3 sterilization and drying, S4 crushing and sieving, and S5 total mixing treatment are all performed synchronously with the original nine kinds of medicinal materials; in the total mixing, ligusticum fine powder and cortex moutan fine powder are premixed according to the "equal addition method", honeysuckle fine powder, rhizoma paridis fine powder, and lobelia fine powder are premixed, and finally the remaining medicinal material fine powder is combined and mixed.