External use medicine composition for clearing heat, removing swelling and resolving stasis, and application and preparation method thereof

Abstract

This invention provides a topical medicine composition for clearing heat, reducing swelling, and resolving blood stasis in the acute phase, along with its application and preparation method, belonging to the field of traditional Chinese medicine formulation technology. This topical medicine composition for clearing heat, reducing swelling, and resolving blood stasis in the acute phase consists of the following raw material components in parts by weight: 5-8 parts raw Phellodendron bark, 2-5 parts borneol, 8-12 parts red peony root, 4-8 parts Panax notoginseng tablets, 4-6 parts stir-fried ground beetle, 2-4 parts prepared myrrh, 2-4 parts prepared frankincense, 5-8 parts prepared Arisaema, 8-12 parts Liquidambar formosana, 8-12 parts Angelica dahurica, 8-12 parts peppermint, and 8-12 parts Trichosanthes kirilowii. This topical medicine composition for clearing heat, reducing swelling, and resolving blood stasis in the acute phase selects traditional Chinese medicinal materials with relatively weak blood-activating effects, which can avoid the risk of increased bleeding and swelling during acute use, achieving safe and effective early intervention for ankle or other injuries in the acute phase, thereby shortening the patient's recovery time.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a topical medicine composition for clearing heat, reducing swelling and removing blood stasis, its application and preparation method. Background Technology

[0002] Ankle sprains are common sports injuries in daily life, often caused by excessive twisting of the joint, leading to damage to ligaments, soft tissues, and capillaries. In the acute phase after a sprain (usually 0-72 hours), the local tissues are in a state of bleeding, edema, and inflammation, clinically manifesting as redness, swelling, heat, pain, and functional impairment. Improper treatment at this time can easily worsen the injury and delay healing.

[0003] Traditional Chinese medicine (TCM) considers the core pathogenesis of early-stage ankle or other injuries to be "blood stasis and qi stagnation, and accumulation of heat toxins." Currently, TCM plasters are widely used in the external treatment of ankle or other injuries due to their effects of promoting blood circulation, removing blood stasis, and relaxing muscles and tendons. However, traditional TCM plasters (such as Yunnan Baiyao plaster and musk analgesic plaster) often contain strong blood-activating ingredients such as peach kernel, safflower, and musk, which have a strong warming and dispersing nature and can promote local blood circulation. Using such plasters in the acute phase can actually dilate blood vessels, accelerate bleeding, exacerbate swelling, and even mask deeper tissue damage (such as ligament tears or fractures), delaying diagnosis and treatment. Furthermore, traditional TCM plasters contain little or no heat-clearing herbs, failing to adequately address the core pathogenesis of "heat toxin accumulation."

[0004] Modern medicine typically recommends the "RICE therapy" (including rest, ice packs, pressure bandages, and limb elevation) as the standard treatment principle during the acute phase, and explicitly prohibits the use of traditional Chinese medicine plasters that promote blood circulation. While the RICE therapy effectively controls swelling and pain, it lacks drug intervention, and patients relying solely on it often find the treatment limited and the recovery process slow. Furthermore, commonly used topical nonsteroidal anti-inflammatory drugs (NSAIDs) have significant drawbacks. For example, diclofenac sodium requires application 3-4 times daily, rubbing the ointment into the skin according to the size of the painful area, which is cumbersome. Massage can worsen swelling, and large applications carry the risk of absorption into the bloodstream and causing systemic side effects. Currently, most commercially available traditional Chinese medicine plasters are designed for the chronic phase, lacking products specifically for the acute phase.

[0005] Therefore, developing a topical ointment suitable for the acute phase of ankle or other injuries, which can achieve simultaneous treatment of "clearing heat, reducing swelling, and removing blood stasis" from the perspective of traditional Chinese medicine, has significant clinical significance and market value. Summary of the Invention

[0006] To overcome the problems existing in related technologies, one of the objectives of this invention is to provide a topical medicine composition for clearing heat, reducing swelling and removing blood stasis. This topical medicine composition for clearing heat, reducing swelling and removing blood stasis selects Chinese medicinal materials that have the effects of clearing heat and cooling blood, removing blood stasis and reducing swelling, but have a weak effect of promoting blood circulation. It can avoid the risk of increased bleeding and swelling during the acute phase of use, and achieve safe and effective early intervention in the acute phase of ankle joint or other injuries, thereby shortening the patient's recovery time.

[0007] A topical medicine composition for clearing heat, reducing swelling, and removing blood stasis, comprising the following raw medicinal components in parts by weight: 5-8 parts of raw Phellodendron bark, 2-5 parts of borneol, 8-12 parts of red peony root, 4-8 parts of Panax notoginseng, 4-6 parts of stir-fried ground beetle, 2-4 parts of processed myrrh, 2-4 parts of processed frankincense, 5-8 parts of processed Arisaema, 8-12 parts of Liquidambar formosana, 8-12 parts of Angelica dahurica, 8-12 parts of peppermint, and 8-12 parts of Trichosanthes kirilowii.

[0008] Furthermore, the external medicine composition for clearing heat, reducing swelling, and removing blood stasis is composed of the following raw material components in parts by weight: 6-8 parts of raw Phellodendron bark, 3-5 parts of borneol, 10-12 parts of red peony root, 6-8 parts of Panax notoginseng, 5-6 parts of stir-fried ground beetle, 3-4 parts of prepared myrrh, 3-4 parts of prepared frankincense, 6-8 parts of prepared Arisaema, 10-12 parts of Liquidambar formosana, 10-12 parts of Angelica dahurica, 9-12 parts of peppermint, and 10-12 parts of Trichosanthes kirilowii.

[0009] Furthermore, this topical medicine composition for clearing heat, reducing swelling, and removing blood stasis is composed of the following raw material components in parts by weight: 6 parts raw Phellodendron bark, 3 parts borneol, 10 parts red peony root, 3 parts prepared frankincense, 3 parts prepared myrrh, 5 parts stir-fried ground beetle, 6 parts Panax notoginseng, 6 parts prepared Arisaema heterophyllum, 10 parts Liquidambar formosana, 10 parts Angelica dahurica, 9 parts peppermint, and 10 parts Trichosanthes kirilowii.

[0010] Furthermore, the external medicine composition for clearing heat, reducing swelling, and removing blood stasis is composed of the following raw material components in parts by weight: 5-8 parts of raw Phellodendron bark, 5 parts of borneol, 10-12 parts of red peony root, 3-4 parts of prepared frankincense, 3-4 parts of prepared myrrh, 5-6 parts of stir-fried ground beetle, 4-6 parts of Panax notoginseng, 5-6 parts of prepared Arisaema heterophyllum, 10-12 parts of Liquidambar formosana, 10-12 parts of Angelica dahurica, 12 parts of peppermint, and 10-12 parts of Trichosanthes kirilowii.

[0011] Furthermore, the external medicine composition for clearing heat, reducing swelling and removing blood stasis is composed of the following raw material components in parts by weight: 5 parts of raw Phellodendron bark, 5 parts of borneol, 12 parts of red peony root, 3 parts of prepared frankincense, 4 parts of prepared myrrh, 6 parts of stir-fried ground beetle, 6 parts of Panax notoginseng, 5 parts of prepared Arisaema heterophyllum, 12 parts of Liquidambar formosana, 12 parts of Angelica dahurica, 12 parts of peppermint, and 12 parts of Trichosanthes kirilowii.

[0012] Furthermore, the dosage form of the acute-phase topical medication composition is a spray, a water-based solution, a gel, a liniment, an ointment, a patch, or other pharmaceutically acceptable topical dosage form.

[0013] A second objective of this invention is to provide an application of an acute-phase topical drug composition in the preparation of a medicament for treating acute-phase injuries.

[0014] Furthermore, during the acute phase of injury, the aforementioned acute-phase topical medication composition was used in accordance with the RICE principle for treatment.

[0015] Furthermore, during the acute phase of injury, the treatment with the acute-phase topical medication composition and the ice application step are performed simultaneously; during the non-acute phase of injury, the acute-phase topical medication composition is applied as a hot compress to the affected area at a temperature of 40℃-50℃.

[0016] A third objective of this invention is to provide a method for preparing a topical medicine composition for clearing heat, reducing swelling, and removing blood stasis, used to prepare a plaster of the topical medicine composition for the acute phase as described above;

[0017] The method includes the following steps:

[0018] Obtain the matrix, and heat and stir the matrix until it is completely melted;

[0019] Obtain the active pharmaceutical ingredient according to the specified ratio, and grind the active pharmaceutical ingredient into powder;

[0020] Once the matrix has cooled to 65-70℃, add the raw drug powder to the matrix and stir evenly to obtain a paste.

[0021] The beneficial effects of this invention are:

[0022] The topical medication composition provided by this invention closely addresses the core pathogenesis of "blood stasis and qi stagnation, and heat toxin accumulation" in the early stages of ankle or other injuries. It emphasizes "clearing heat, cooling blood, and resolving blood stasis" while focusing on "relatively weak blood-activating" through scientific formulation of medicinal materials. This allows patients to receive medication treatment during the golden intervention period after injury, accelerating recovery. Peppermint, Phellodendron bark, and borneol are the principal herbs. Phellodendron bark is bitter and cold, a key herb for clearing heat and drying dampness, addressing the heat toxins formed by local blood stasis and heat after a sprain or strain. Borneol is pungent and aromatic, penetrating the skin to guide the other herbs directly to the affected area, and also has heat-clearing and pain-relieving effects. Peppermint is pungent and cool, dispelling wind and heat; its light and dispersing properties help borneol penetrate the medicine and provide a cooling sensation. The three herbs work together to clear and penetrate, jointly resolving the core contradiction of "heat toxins." Red peony root, Panax notoginseng, and Eupolyphaga sinensis are the assistant herbs; these three herbs form a powerful force for resolving blood stasis and reducing swelling. Red peony root clears heat, cools the blood, disperses blood stasis, and relieves pain; Panax notoginseng resolves blood stasis, stops bleeding, reduces swelling, and relieves pain, with the characteristic of not leaving blood stasis; Eupolyphaga sinensis is good at breaking up blood stasis and removing blood stasis, and is effective for deep stagnation and injury. Together, they enhance the blood-resolving and swelling-reducing power of the principal herb. Myrrh, frankincense, Arisaema heterophyllum, Trichosanthes kirilowii, and Angelica dahurica are adjuvant herbs, with a small amount of myrrh and frankincense added. The two complement each other, promoting qi and blood circulation, reducing swelling and promoting tissue regeneration, and specifically targeting pain caused by "qi stagnation and blood stasis". Arisaema heterophyllum dries dampness, resolves phlegm, reduces swelling and dissipates nodules, and is good at removing swelling caused by the mutual binding of phlegm and blood stasis. Trichosanthes kirilowii clears heat, generates fluids, reduces swelling and drains pus, assists Phellodendron chinense in clearing heat, and also prevents heat toxin from rotting flesh and forming pus. Angelica dahurica is pungent and warm, and can dispel cold, relieve pain, reduce swelling and drain pus. Its pungent and dispersing nature can help the medicine penetrate and prevent the overall formula from being too cold. Liquidambar formosana is the guiding herb, which can open up the twelve meridians, is good at dispelling wind, opening up the collaterals, promoting diuresis and reducing swelling, and guides the medicine to pass through the meridians of the whole body, especially good at clearing the joints of the limbs. This composition combines warming and cooling herbs, with a focus on cooling: although it includes warming herbs such as Angelica dahurica and frankincense, the overall medicinal properties lean towards cooling (Phellodendron chinense, Paeonia lactiflora, Trichosanthes kirilowii, Mentha haplocalyx, etc.). This clearly points to the pathogenesis of "blood stasis transforming into heat" in the acute phase. Panax notoginseng, Eupolyphaga sinensis, frankincense, and myrrh can promote blood circulation, relieve pain, and heal tendons and bones, but their medicinal properties are relatively mild, lacking the warming and dispersing properties of herbs like safflower and musk. This avoids the risk of increased bleeding and swelling due to excessive blood circulation when capillary bleeding has not yet stopped.

[0023] This application also provides a method for preparing the above-mentioned topical medicine composition for clearing heat, reducing swelling and removing blood stasis. The ointment prepared by this method can be used for the treatment of acute injuries, thereby shortening the patient's recovery time and improving the efficiency of the patient's recovery. Attached Figure Description

[0024] Figure 1 This is a flowchart of the preparation of the topical medicine composition plaster provided in the embodiments of this application.

[0025] Figure 2 Photographs showing the measurement of ankle swelling in mice;

[0026] Figure 3 A statistical graph showing the changes in body weight of mice in each group after using the topical medicine composition for clearing heat, reducing swelling and removing blood stasis of this application;

[0027] Figure 4 A schematic diagram showing the effect of using the topical medicine composition for clearing heat, reducing swelling, and removing blood stasis of this application on the swelling of the ankle joint in mice;

[0028] Figure 5 The image shows the swelling of the ankle joint in mice after using the topical medicine composition for clearing heat, reducing swelling and removing blood stasis as described in this application.

[0029] Figure 6 A schematic diagram showing the effect of the topical medicine composition for clearing heat, reducing swelling, and removing blood stasis of this application on the serum IL-1β level in mice;

[0030] Figure 7 Schematic diagram of HE staining results for mouse ankle joint tissue;

[0031] Figure 8 A histopathological scoring diagram of mouse ankle joint tissue;

[0032] Figure 9 A schematic diagram showing the results of Safranin-Fix-Green staining of mouse ankle cartilage;

[0033] Figure 10 This is a protein comparison diagram of the mouse ankle joint;

[0034] Figure 11 This is a schematic diagram showing the relative expression levels of NF-κB p65 protein in the mouse ankle joint. Detailed Implementation

[0035] Preferred embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While preferred embodiments of the invention are shown in the drawings, it should be understood that the invention may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that the invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0036] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The singular forms “a,” “the,” and “the” used in this invention and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used herein refers to and includes any or all possible combinations of one or more of the associated listed items.

[0037] It should be understood that although the terms "first," "second," "third," etc., may be used in this invention to describe various information, this information should not be limited to these terms. These terms are only used to distinguish information of the same type from one another. For example, without departing from the scope of this invention, first information may also be referred to as second information, and similarly, second information may also be referred to as first information. Thus, features defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0038] Currently, traditional Chinese medicine plasters are widely used in the topical treatment of acute ankle sprains and other acute injuries due to their effects of promoting blood circulation, removing blood stasis, and relaxing muscles and tendons. However, traditional Chinese medicine plasters (such as Yunnan Baiyao plaster and musk analgesic plaster) often contain strong blood-activating ingredients such as safflower and musk, which have a warming and penetrating nature and can promote local blood circulation. Using such plasters in the acute phase can actually dilate blood vessels, accelerate bleeding, and exacerbate swelling, even masking deeper tissue damage (such as ligament tears or fractures), delaying diagnosis and treatment. Furthermore, traditional Chinese medicine plasters do not contain or contain only a small amount of heat-clearing herbs, failing to adequately address the core pathogenesis of "heat toxin accumulation." Modern medicine generally recommends the "RICE therapy" (including rest, ice packs, pressure bandages, and elevation of the affected limb) as the standard treatment principle in the acute phase and explicitly prohibits the use of blood-activating Chinese medicine plasters. Although the RICE therapy can effectively control swelling and pain symptoms, it lacks drug intervention, and patients who only receive the RICE therapy often feel that the treatment is limited and the later recovery process is slow. Furthermore, commonly used topical nonsteroidal anti-inflammatory drugs (NSAIDs) have significant drawbacks. For example, diclofenac sodium requires application by rubbing the ointment into the skin according to the size of the painful area, and needs to be used 3-4 times daily. This method is rather cumbersome, and rubbing can worsen swelling. Applying it to large areas also carries the risk of absorption into the bloodstream and causing systemic side effects. Currently, most Chinese herbal plasters on the market are designed for the chronic phase, and there is a lack of Chinese herbal plasters specifically for the acute phase.

[0039] Based on this, this application provides a topical medicine composition for clearing heat, reducing swelling, and removing blood stasis.

[0040] This topical medicine composition consists of the following raw material components in parts by weight: 5-8 parts raw Phellodendron bark, 2-5 parts borneol, 8-12 parts red peony root, 4-8 parts Panax notoginseng, 4-6 parts stir-fried ground beetle, 2-4 parts prepared myrrh, 2-4 parts prepared frankincense, 5-8 parts prepared Arisaema, 8-12 parts Liquidambar formosana, 8-12 parts Angelica dahurica, 8-12 parts peppermint, and 8-12 parts Trichosanthes kirilowii.

[0041] It should be noted that this weight can be expressed in grams, kilograms, or other units, or as a proportional weight. For example, no limitation is made here; it can be set as needed. Proportional weights include, for example, 10g, 100g, or 200g. Specifically, for example, 30-90g of raw Phellodendron bark is equivalent to 3... 10g-9 10g, which is the corresponding weight portion.

[0042] In the early stages of acute injury, this topical medication composition is safe and effective, overcoming the traditional contraindication that "plasters are contraindicated in the acute phase." This composition closely addresses the core pathogenesis of "blood stasis and qi stagnation, and heat toxin accumulation" in the early stages of ankle or other injuries. It emphasizes "clearing heat, cooling blood, and removing blood stasis" while being less focused on "invigorating blood circulation," scientifically combining medicinal materials to ensure patients receive optimal treatment during the golden intervention period and accelerate recovery.

[0043] Among them, peppermint, phellodendron bark, and borneol are the principal herbs. Phellodendron bark is bitter and cold, and is an essential herb for clearing heat and drying dampness, addressing the heat toxicity formed by local bruising and heat after a sprain or strain. Borneol is pungent and aromatic, penetrating the skin and guiding the other herbs directly to the affected area, while also having the effect of clearing heat and relieving pain. Peppermint is pungent and cool, dispelling wind and heat; its light and dispersing properties help borneol penetrate the medicinal properties and bring a cooling sensation. The three herbs work together to clear heat and penetrate the skin, jointly resolving the core contradiction of "heat toxicity."

[0044] Red peony root, Panax notoginseng, and ground beetle are the assistant herbs, forming a powerful force for resolving blood stasis and reducing swelling. Red peony root clears heat, cools the blood, disperses blood stasis, and relieves pain; Panax notoginseng resolves blood stasis, stops bleeding, reduces swelling, and relieves pain, with the characteristic of not leaving blood stasis; ground beetle is good at breaking up blood stasis and removing blood stasis, and is effective for deep stagnation and injury. Together, they enhance the blood-resolving and swelling-reducing power of the principal herb.

[0045] Myrrh, frankincense, arisaema, trichosanthes root, and angelica root are used as adjuvant herbs, with a small amount of myrrh and frankincense added. These two herbs work synergistically to promote qi and blood circulation, reduce swelling and promote tissue regeneration, specifically targeting pain caused by "qi stagnation and blood stasis." Arisaema dries dampness, resolves phlegm, reduces swelling and dissipates nodules, effectively eliminating swelling caused by the mutual binding of phlegm and blood stasis. Trichosanthes root clears heat, generates fluids, reduces swelling and drains pus, assisting phellodendron bark in clearing heat and preventing the formation of pus from the putrefaction of heat toxins. Angelica root, being pungent and warm, can dispel cold, relieve pain, reduce swelling and drain pus; its pungent and dispersing nature helps the medicine penetrate deeply and prevents the overall formula from being too cold. Liquidambar formosana is used as the guiding herb, capable of unblocking the twelve meridians, effectively dispelling wind, clearing the collaterals, promoting diuresis and reducing swelling, guiding the other herbs through the meridians throughout the body, especially adept at clearing the joints of the limbs. This composition uses both warm and cold herbs, with cold as the primary element: although warm herbs such as angelica root and frankincense are used in the formula, the overall medicinal properties are biased towards cold (phellodendron bark, red peony root, trichosanthes root, and mint, etc.), clearly indicating the pathogenesis of "stasis transforming into heat" in the acute phase. Panax notoginseng, ground beetle, frankincense, and myrrh can promote blood circulation, relieve pain, and heal tendons and bones. However, their medicinal properties are relatively mild, lacking the warming and penetrating properties of herbs like safflower and musk. This avoids the risk of increased bleeding and swelling due to excessive blood circulation when capillary bleeding has not yet stopped. Clinical data confirms that this formula is safe to use in the acute phase and can maximize the therapeutic effect during the golden recovery period.

[0046] After acute treatment, this topical medication composition can continue to be used during non-acute injury periods. At this time, the composition can continue to promote blood circulation, remove blood stasis, and reduce swelling, which helps to shorten the recovery time and improve the recovery efficiency. In this case, there is no need to switch to other medications specifically for non-acute periods, making it convenient to use and cost-effective.

[0047] Specifically, after 72 hours (acute phase) following injury, the body enters a non-acute phase focused on tissue repair and functional recovery. At this time, the local "heat toxin" has cleared, and the condition transforms into "blood stasis and blocked meridians." The mechanism of action of this topical medication composition is adaptively adjusted accordingly.

[0048] 1) The formula is dominated by resolving blood stasis and dissipating nodules: Panax notoginseng and Eupolyphaga sinensis are the core ingredients, which strongly promote the absorption of hematomas and stagnant tissues by activating the fibrinolytic system and improving microcirculation. Frankincense and myrrh continuously inhibit chronic inflammation and prevent soft tissue adhesions.

[0049] 2) Initiating internal repair: Ingredients such as Panax notoginseng, frankincense, and myrrh can upregulate the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor, promote capillary angiogenesis and collagen synthesis, and provide a material basis for the structural repair of soft tissues such as ligaments and tendons.

[0050] Therefore, the composition of the present invention has the ability to intervene throughout the entire process: in the acute phase, it clears heat and cools blood to prevent aggravation, and in the non-acute phase, it promotes blood circulation and removes blood stasis to promote repair, thus realizing "one medicine for two purposes", simplifying the treatment plan and optimizing the rehabilitation process.

[0051] The drug claimed in this application is not a simple combination of medicinal materials, but rather achieves synergistic effects through a combination logic of "treating the root cause by clearing heat and cooling the blood, and treating the symptoms by gently resolving blood stasis." The heat-clearing components can reduce vascular permeability, thereby alleviating tissue fluid leakage at its source. The combination of borneol with frankincense and myrrh enhances the analgesic effect. The gentle blood-activating components can promptly initiate the tissue repair process after inflammation is controlled, clearing blood stasis and promoting ligament tissue regeneration.

[0052] The topical medication composition can be in the form of a spray, aqueous solution, gel, liniment, ointment, plaster, or other pharmaceutically acceptable topical dosage form. Preferably, the topical medication composition is a plaster gel for ease of preparation, storage, and use. In other embodiments, it can be prepared as a medicinal wine, plaster, or spray, etc., and is not limited thereto.

[0053] In a preferred embodiment, such as Figure 1 As shown, the topical pharmaceutical composition is prepared as a plaster, which further includes a base. Preferably, the base is selected from one or more of pharmaceutical petrolatum, lanolin, and polyethylene glycol. In other embodiments, the base may also be sesame oil or other lipids that can be formed into a paste.

[0054] Furthermore, the polyethylene glycols include polyethylene glycol 4000 and polyethylene glycol 6000, wherein polyethylene glycol 4000 and polyethylene glycol 6000 are mixed in a weight ratio of 1:1 to 3:1.

[0055] In practical applications, petrolatum is a powerful occlusive agent that forms a strong, water-impermeable, oily protective film on the skin's surface. It effectively reduces transepidermal water loss, allowing the stratum corneum to fully hydrate and soften. The increased intercellular spaces in the hydrated stratum corneum promote the penetration and absorption of medications, thereby enhancing their efficacy. This film effectively isolates the skin from external irritants, bacteria, and contaminants, providing additional protection for minor skin abrasions or sensitive skin that may have been exposed to acute injury, helping to prevent infection and reduce irritation.

[0056] Alternatively, a specific ratio (2:1) mixture of polyethylene glycol 4000 and 6000 can be used as the base. This base helps to precisely control the melting point and consistency of the ointment, ensuring that it softens and adheres to the skin at body temperature while remaining stable and non-flowing at room temperature. It exhibits stable physicochemical properties and is easy to apply and wash off. The polyethylene glycol base itself has good water solubility and transdermal absorption-enhancing effects, helping drug components to penetrate and absorb better without causing contraindications with traditional Chinese medicine ingredients. This base is non-irritating, has low allergenicity, and does not contain the tackifiers found in traditional rubber plasters, greatly reducing the risk of contact dermatitis in patients with allergies, resulting in high patient compliance.

[0057] The petrolatum or polyethylene glycol and other modern matrix materials have stable chemical properties, long shelf life, and a refreshing texture that is easy to control in terms of consistency, which meets the needs of modern pharmaceutical production and consumption.

[0058] Furthermore, the external medicinal composition is formulated as follows: 6-8 parts by weight of raw Phellodendron bark, 3-5 parts by weight of borneol, 10-12 parts by weight of Paeonia lactiflora, 6-8 parts by weight of Panax notoginseng, 5-6 parts by weight of stir-fried Eupolyphaga sinensis, 3-4 parts by weight of processed myrrh, 3-4 parts by weight of processed frankincense, 6-8 parts by weight of processed Arisaema heterophyllum, 10-12 parts by weight of Liquidambar formosana, 10-12 parts by weight of Angelica dahurica, 9-12 parts by weight of Mentha haplocalyx, and 10-12 parts by weight of Trichosanthes kirilowii. At this point, all components are in high doses, resulting in a relatively strong effect in clearing heat and reducing swelling, which is more conducive to reducing swelling at the affected area and shortening the recovery period.

[0059] Furthermore, the topical medication composition is applied to acute ankle sprains and other acute injuries; during the acute phase of these injuries, the topical medication composition is used in accordance with the RICE principle to accelerate the recovery of the affected area.

[0060] In some embodiments, the time interval between the application of the topical medication composition and the ice application step is no more than two hours to enhance the heat-clearing and swelling-reducing effect. The topical medication composition and the ice application step work synergistically to enhance the efficacy of peppermint, phellodendron bark, borneol, and the heat-clearing and blood-cooling effects of other ingredients. Combined with the ice application, this significantly enhances the swelling-reducing and analgesic effects after injury, shortening the recovery period.

[0061] Preferably, the time interval between the application of the topical medication composition and the ice application step is no more than one hour, further enhancing the anti-swelling and analgesic effects.

[0062] Preferably, the treatment with the topical medication composition and the ice application step are performed simultaneously. In some embodiments, when the topical medication composition is in the form of an ointment, the ointment is wrapped with gauze or other cloth after application, and ice cubes can be placed on top of the ointment to treat the affected area together. In some embodiments, the liquid of the topical medication composition can be directly soaked in gauze or other cloth and then applied to the affected area, followed by applying ice cubes to the affected area through the gauze or other cloth. In some embodiments, when the topical medication composition is in the form of a patch, the patch is applied to the affected area, and then ice cubes are placed on the back of the patch. Other methods can be used to perform the treatment with the topical medication composition and the ice application step simultaneously, which are not listed here but used as needed.

[0063] The topical medication composition of this application can be used within 24 hours of the acute phase, applying it to the affected area once a day for 4-6 hours each time, continuing for 7 days, which can promote good recovery of the affected area. In this case, there is no need to frequently change the medication or repeatedly massage it, making it simple and convenient to use. It also has minimal irritation to the skin and muscles, few side effects, and avoids adverse reactions such as aggravated swelling and pain caused by massage. This is mainly because the topical medication composition of this application has good drug penetration, allowing the efficacy to reach deep into muscles and other tissues without massage, which is conducive to the smooth recovery of the affected area. In addition, during the 4-6 hour application period, multiple ice packs can be applied simultaneously, each for 15-20 minutes, with intervals of 1-2 hours, which can greatly enhance the treatment of the affected area.

[0064] It should be noted that the combined use of this topical medication composition and the ice application step is not a simple additive effect, but rather produces a synergistic effect by complementing each other's weaknesses. The mechanism of action is analyzed as follows:

[0065] 1. Immediate analgesia and cooling

[0066] The effects of ice packs: 1) Lowering local temperature, inhibiting nerve ending conduction velocity, and providing rapid pain relief. 2) Constricting blood vessels, reducing throbbing pain.

[0067] Actions of the topical medication composition: 1) Borneol and menthol activate skin cold receptors (TRPM8 channels), producing a sustained "chemical cooling sensation". 2) Frankincense, myrrh, and Panax notoginseng inhibit the synthesis of peripheral pain-inducing substances (such as PGE2).

[0068] Synergistic effect: Dual-channel continuous analgesia, physical cooling provides immediate and powerful analgesia, and the cooling sensation of the drug and analgesic ingredients provide a lasting effect, covering the interval between ice application.

[0069] 2. Control bleeding and swelling

[0070] The effects of ice packs include: 1) Strongly constricting capillaries and reducing bleeding in the acute phase; 2) Lowering tissue metabolic rate and alleviating the initial inflammatory response.

[0071] Actions of the topical medication combination: 1) Phellodendron bark and red peony root reduce vascular permeability, thereby reducing inflammatory exudation through biochemical pathways. 2) Panax notoginseng has a bidirectional regulatory effect of "removing blood stasis and stopping bleeding," which can promote the absorption of blood stasis without aggravating bleeding.

[0072] Synergistic effect: Ice application forcibly constricts blood vessels, while the medication strengthens the blood vessel walls by reducing inflammation and permeability, thus inhibiting the extravasation of tissue fluid and blood from the source.

[0073] 3. Anti-inflammatory and heat-clearing effects

[0074] Effects of ice application: 1) Slows down local metabolism and reduces the release rate of inflammatory factors. 2) However, the effect is superficial and may rebound after cessation.

[0075] Actions of the topical medication combination: 1) Phellodendron bark, red peony root, and trichosanthes root directly inhibit key inflammatory pathways such as NF-κB and downregulate core inflammatory factors such as IL-1β and TNF-α. 2) Targeting the pathogenesis of "blood stasis transforming into heat," it clears away heat toxins.

[0076] Synergistic effect: Treating both the symptoms and the root cause, ice packs temporarily "suppress" the inflammatory response, while the medication "blocks" inflammation at the molecular level, achieving long-term anti-inflammatory effects and avoiding rebound.

[0077] 4. Drug penetration and utilization

[0078] The effects of ice packs: 1) Low temperatures temporarily tighten the stratum corneum of the skin, which is traditionally not conducive to drug absorption.

[0079] Actions of the topical medication composition: 1) Borneol and menthol are potent transdermal penetration enhancers that can overcome the penetration barrier caused by low temperatures. 2) When local blood flow is restored after ice application (reactive hyperemia), the drug absorption efficiency may actually increase.

[0080] Synergistic effect: The transdermal penetration enhancer of the drug ensures that the active ingredients can penetrate efficiently and reach deep damaged tissues even under ice application conditions.

[0081] Furthermore, during the acute phase of injury, the topical medication composition is refrigerated at 0°C-20°C until the temperature is suitable for skin contact before application to the affected area. Under these conditions, the medication's heat-clearing effect is enhanced, thereby strengthening its anti-swelling and analgesic effects.

[0082] Furthermore, during non-acute injury periods, the topical medication composition is applied as a hot compress to the affected area at a temperature of 40℃-50℃. Under these conditions, the hot compress enhances the therapeutic effect, causing local vasodilation, increased blood flow, and accelerated metabolism. Menthol and borneol exhibit stronger transdermal absorption under warm conditions, efficiently delivering blood-activating and stasis-removing components (such as notoginseng saponins and boswellic acid) into deep tissues. The warm environment enhances the bioactivity and reaction rate of the drug components, creating an "external heat and internal penetration" effect. The hot compress provides physical stimulation, while the cooling sensation of menthol balances the burning sensation, preventing overheating damage and improving patient tolerance, thus allowing for longer and more effective heat therapy. Therefore, the combination of the "physical unblocking" effect of the hot compress and the "chemical stasis removal" effect of the medication greatly accelerates the functional recovery process.

[0083] Furthermore, the "pungent and cooling" properties of peppermint can help disperse local "stagnant qi." Through its excellent transdermal penetration, it can effectively enhance the blood-activating, stasis-removing, and swelling-reducing effects of the formula, and improve the user experience, making the stasis-removing process more "refreshing" and less likely to generate heat. Combined with the blood circulation-promoting effect of hot compresses and the powerful "guiding" and penetrating effects of peppermint, the blood-activating, stasis-removing, and swelling-reducing effects can be greatly enhanced.

[0084] Menthol in peppermint is an excellent transdermal penetration enhancer. It can temporarily increase the permeability of the stratum corneum, helping other blood-activating and stasis-removing ingredients in the prescription (such as frankincense, myrrh, and ground beetle) to penetrate the skin more effectively and reach the deeper bruised tissue. This is equivalent to opening a "highway" for the drug, greatly improving the overall bioavailability of the drug.

[0085] Peppermint produces a "cooling" sensation to balance the burning sensation of a hot compress: Hot compresses can sometimes cause excessive burning and discomfort on the skin. The cooling sensation of peppermint can create a complex feeling of "cool first, then hot" or "cool on the outside, penetrating inside" with the warmth of the hot compress, improving comfort during use and allowing patients to tolerate longer or higher temperatures of the hot compress, thereby indirectly enhancing the effect of the hot compress.

[0086] Peppermint can also provide mild local anesthesia and relief from itching: menthol has mild anesthetic and antipruritic effects, which can relieve itching or dull pain that may occur during the recovery period of an injury.

[0087] Furthermore, during the injury period, applying cold compresses during the acute phase and applying hot compresses during the non-acute phase can greatly promote the reduction of swelling and repair of the affected area, thus shortening the recovery period.

[0088] Furthermore, the temperature for applying heat should be between 40℃ and 45℃ to prevent burns.

[0089] There are various forms of hot compresses, such as applying the ointment of the topical drug composition of this application to a moistened hot towel; or directly soaking the topical drug composition in hot water, cooling it to 40℃-50℃, and then applying it to the affected area with a towel soaked in the solution; if the affected area is convenient to soak in water, it can also be directly soaked in a solution containing the topical drug composition at 40℃-50℃ for treatment. Other forms of hot compresses are also possible, which will not be listed here.

[0090] When the external application formula is adjusted to include: 5-8 parts by weight of raw Phellodendron bark, 5 parts by weight of borneol, 10-12 parts by weight of Paeonia lactiflora, 3-4 parts by weight of processed frankincense, 3-4 parts by weight of processed myrrh, 5-6 parts by weight of stir-fried Eupolyphaga sinensis, 4-6 parts by weight of Panax notoginseng, 5-6 parts by weight of processed Arisaema heterophyllum, 10-12 parts by weight of Liquidambar formosana, 10-12 parts by weight of Angelica dahurica, 12 parts by weight of Mentha haplocalyx, and 10-12 parts by weight of Trichosanthes kirilowii, using this formula in conjunction with cold compresses during the acute phase enhances its heat-clearing effect, further reducing swelling and pain, and shortening the recovery period. When using this formula for hot compresses during the non-acute phase, the higher dosage of borneol and Mentha, along with its enhanced blood-activating and stasis-removing effects, further promotes stasis removal and swelling reduction, thereby further accelerating the healing process and shortening the recovery period.

[0091] This application also provides a method for preparing a topical medicine composition for clearing heat, reducing swelling, and removing blood stasis, used to prepare a plaster of the above-mentioned topical medicine composition;

[0092] The method includes the following steps:

[0093] S100. Obtain the matrix and heat and stir the matrix until it is completely melted;

[0094] S200. Obtain the active pharmaceutical ingredient according to the specified ratio and grind it into powder;

[0095] S300. After the matrix cools to 65-70℃, add the raw drug powder to the matrix and stir evenly to obtain the paste.

[0096] Furthermore, the preparation method also includes:

[0097] S400. After the ointment has cooled to room temperature, fill it into containers and affix a label for external use.

[0098] S500. Pack several individual small jars of ointment into a plastic bag, and then affix a special label to the outside of the plastic bag.

[0099] Individually packaged jars ensure that each use preserves the remaining ointment, maintaining product hygiene and preventing spoilage from repeated contact. The lightweight jars are convenient to carry, allowing users to use the ointment as needed and easily control the dosage per application.

[0100] Plastic sealable bags (especially vacuum-sealed ones) effectively isolate oxygen and moisture, slowing down drug oxidation and matrix rancidity, thereby extending the product's shelf life. The flexibility of multi-can packaging using plastic sealable bags makes them suitable for single-person treatment courses.

[0101] Example 1

[0102] The preparation method of this topical medicine composition for clearing heat, reducing swelling, and removing blood stasis is as follows:

[0103] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0104] Raw Phellodendron bark 5g, Borneol 2g, Red peony root 8g, Prepared frankincense 2g, Prepared myrrh 2g, Fried ground beetle 4g, Panax notoginseng slices 4g, Prepared Arisaema heterophyllum 5g, Liquidambar formosana 8g, Angelica dahurica 8g, Mentha haplocalyx 8g, Trichosanthes kirilowii 8g;

[0105] Obtain the petrolatum base and heat and stir until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0106] Then the ointment is filled and labeled:

[0107] In this embodiment, each component is used at the minimum dosage.

[0108] Example 2

[0109] The preparation method of this topical medicine composition for clearing heat, reducing swelling, and removing blood stasis is as follows:

[0110] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0111] Raw Phellodendron bark 6g, Borneol 3g, Red peony root 10g, Prepared frankincense 3g, Prepared myrrh 3g, Fried ground beetle 5g, Panax notoginseng slices 6g, Prepared arisaema 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Mentha haplocalyx 9g, Trichosanthes kirilowii 10g;

[0112] Obtain the petrolatum base and heat and stir until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0113] Then the ointment is filled and labeled:

[0114] The dosages of the heat-clearing, swelling-reducing, and blood-stasis-removing ointment in this embodiment are all medium-dose. This formulation of the ointment emphasizes both clearing heat and removing blood stasis: the medium-dose formula retains the characteristics of the main formula for clearing heat and cooling blood (such as Phellodendron bark, Red peony root, and Trichosanthes root) while also taking into account the medicinal power of removing blood stasis and reducing swelling (such as Panax notoginseng, Eupolyphaga sinensis, Frankincense, and Myrrh). Compared with the low-dose formula, its efficacy is stronger; compared with the high-dose formula, its medicinal properties are milder and less likely to cause excessive stimulation. This formulation of the heat-clearing, swelling-reducing, and blood-stasis-removing ointment is suitable for most patients with acute injuries, especially typical cases with both blood stasis and heat, and significant swelling and pain.

[0115] Example 3

[0116] The preparation method of this topical medicine composition for clearing heat, reducing swelling, and removing blood stasis is as follows:

[0117] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0118] Raw Phellodendron bark 8g, Borneol 5g, Red peony root 12g, Prepared frankincense 4g, Prepared myrrh 4g, Fried ground beetle 6g, Panax notoginseng slices 8g, Prepared arisaema 8g, Liquidambar formosana 12g, Angelica dahurica 12g, Mentha haplocalyx 12g, Trichosanthes kirilowii 12g;

[0119] Obtain the petrolatum base and heat and stir until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0120] Then the ointment is filled and labeled:

[0121] In this embodiment, each component is at its maximum dose.

[0122] Example 4

[0123] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0124] Obtain the following raw material components in grams: 6 grams of raw Phellodendron bark, 3 grams of borneol, 10 grams of red peony root, 8 grams of Panax notoginseng tablets, 5 grams of stir-fried ground beetle, 2 grams of prepared myrrh, 4 grams of prepared frankincense, 5 grams of prepared Arisaema heterophyllum, 8 grams of Liquidambar formosana, 8 grams of Angelica dahurica, 8 grams of peppermint, and 12 grams of Trichosanthes kirilowii.

[0125] Obtain the petrolatum base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0126] Then the paste is filled and labeled.

[0127] In this embodiment, borneol is used in a low dose, Panax notoginseng in a high dose, processed frankincense in a high dose, processed Arisaema heterophyllum in a low dose, Liquidambar formosana in a low dose, Angelica dahurica in a low dose, and Trichosanthes kirilowii in a high dose. The dosage for promoting blood circulation and removing blood stasis is increased, which is suitable for patients with more severe symptoms of blood stasis.

[0128] Example 5

[0129] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0130] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0131] Raw Phellodendron bark 5g, Borneol 5g, Red peony root 12g, Prepared frankincense 3g, Prepared myrrh 4g, Fried ground beetle 6g, Panax notoginseng slices 6g, Prepared arisaema 5g, Liquidambar formosana 12g, Angelica dahurica 12g, Mentha haplocalyx 12g, Trichosanthes kirilowii 12g;

[0132] Obtain the petrolatum base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0133] Then the paste is filled and labeled.

[0134] In this embodiment, peppermint, borneol, red peony root, prepared myrrh, stir-fried ground beetle, prepared arisaema, liquidambar formosana, and angelica dahurica are used in high doses to enhance heat-clearing effects and are suitable for patients with severe heat-toxicity symptoms.

[0135] Example 6

[0136] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0137] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0138] 5g raw Phellodendron bark, 3g borneol, 10g red peony root, 3g prepared frankincense, 4g prepared myrrh, 5g stir-fried ground beetle, 4g Panax notoginseng slices, 6g prepared Arisaema heterophyllum, 10g Liquidambar formosana, 10g Angelica dahurica, 12g peppermint, 12g Trichosanthes kirilowii.

[0139] Obtain the petrolatum base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0140] Then the ointment is filled and labeled:

[0141] In this embodiment, the dosages are as follows: high dose of peppermint, medium dose of raw phellodendron bark, medium dose of red peony root, medium dose of processed frankincense, high dose of processed myrrh, medium dose of stir-fried ground beetle, low dose of Panax notoginseng tablets, and high dose of Trichosanthes kirilowii root.

[0142] Example 7

[0143] The preparation method of this topical medicine composition for clearing heat, reducing swelling, and removing blood stasis is as follows:

[0144] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0145] Raw Phellodendron bark 6g, Borneol 3g, Red peony root 10g, Prepared frankincense 3g, Prepared myrrh 3g, Fried ground beetle 5g, Panax notoginseng 6g, Prepared arisaema 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Mentha haplocalyx 9g, Trichosanthes kirilowii 10g;

[0146] Obtain the sesame oil base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain the paste;

[0147] Then the paste is filled and labeled.

[0148] In this embodiment, the external medicine composition for clearing heat, reducing swelling, and removing blood stasis is selected from the traditional Chinese medicine ingredients used in Example 2, and sesame oil is used instead of petroleum jelly as the base. Sesame oil itself has the effects of moisturizing dryness and detoxifying, and has good compatibility with traditional Chinese medicine. The resulting plaster is traditionally believed to have better permeability, but after plastering, the hardness and viscosity of the plaster are poor, which affects the efficacy.

[0149] Comparative Example 1

[0150] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0151] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0152] Raw Phellodendron bark 6g, Borneol 3g, Red peony root 10g, Panax notoginseng slices 6g, Fried ground beetle 5g, Prepared myrrh 3g, Prepared frankincense 3g, Prepared arisaema 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Trichosanthes kirilowii 10g;

[0153] Obtain the petrolatum base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0154] Then the paste is filled and labeled.

[0155] The heat-clearing, swelling-reducing, and blood-stasis-removing ointment provided in this comparative example does not contain menthol.

[0156] Compared to the full formula, the heat-clearing, swelling-reducing, and blood-stasis-removing effects of this modified formula are significantly weakened. For symptoms of redness, swelling, heat, and pain caused by heat toxicity, the rate of swelling reduction is slower, and the analgesic effect is particularly diminished. Therefore, peppermint is indispensable in synergistically clearing heat.

[0157] Comparative Example 2

[0158] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0159] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0160] Borneol 3g, red peony root 10g, Panax notoginseng slices 6g, stir-fried ground beetle 5g, prepared myrrh 3g, prepared frankincense 3g, prepared arisaema 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Trichosanthes kirilowii 10g;

[0161] Obtain the petrolatum base and heat and stir until completely melted; after the base cools to 65-70℃, add the active pharmaceutical ingredient powder to the base and stir evenly to obtain a paste.

[0162] Then the paste is filled and labeled.

[0163] The heat-clearing, swelling-reducing, and blood-stasis-removing ointment provided in this comparative example lacks menthol and raw phellodendron bark. This formula essentially transforms into an ointment primarily focused on promoting blood circulation and removing blood stasis, rendering it almost ineffective for conditions with pronounced "heat" symptoms (such as the early stages of acute inflammation). Its applicability is significantly narrowed, failing to achieve the combined treatment of "clearing heat" and "removing blood stasis." Experimental verification shows that ointments without menthol and raw phellodendron bark have severely weakened or lost their "heat-clearing and blood-cooling" effects, thus becoming ordinary external ointments primarily focused on "promoting blood circulation and removing blood stasis," no longer suitable for the core pathogenesis of early-stage acute injuries.

[0164] Comparative Example 3

[0165] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0166] Raw Phellodendron bark 6g, Red peony root 10g, Prepared frankincense 3g, Prepared myrrh 3g, Fried ground beetle 5g, Panax notoginseng slices 6g, Prepared Arisaema heterophyllum 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Mentha haplocalyx 9g, Trichosanthes kirilowii 10g;

[0167] Obtain the petrolatum base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0168] Then the paste is filled and labeled.

[0169] The heat-clearing, swelling-reducing, and blood-stasis-removing ointment provided in this comparative example does not contain borneol.

[0170] Compared to the complete formula, the heat-clearing, swelling-reducing, and blood-stasis-removing ointment provided in this comparative ratio has significantly weakened heat-clearing and blood-cooling effects. Borneol plays multiple crucial roles in this topical medication composition, serving as a pivotal ingredient to ensure efficacy. Its presence allows the medication to safely and deeply penetrate the skin during the acute phase, enhances the blood-activating and stasis-removing abilities of the herbal remedies during the non-acute phase, and assists in clearing heat. Without borneol, its heat-clearing, swelling-reducing, and blood-stasis-removing effects are greatly diminished.

[0171] Comparative Example 4

[0172] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0173] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0174] Raw Phellodendron bark 6g, Borneol 3g, Red peony root 10g, Fried ground beetle 5g, Prepared myrrh 3g, Prepared frankincense 3g, Prepared arisaema 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Peppermint 9g, Trichosanthes kirilowii 10g;

[0175] Obtain the petrolatum base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0176] Then the paste is filled and labeled.

[0177] The heat-clearing, swelling-reducing, and blood-stasis-removing ointment provided in this comparative example does not contain Panax notoginseng tablets. Panax notoginseng is known as an essential medicine for treating wounds, and its effects in promoting blood circulation and relieving pain are remarkable. Without Panax notoginseng, the ointment provides slower relief from severe pain in the early stages of injury.

[0178] Comparative Example 5

[0179] The preparation method of this heat-clearing, swelling-reducing, and blood-stasis-removing ointment is as follows:

[0180] Obtain the following parts by weight of active pharmaceutical ingredient components:

[0181] Raw Phellodendron bark 6g, Borneol 3g, Red peony root 10g, Panax notoginseng slices 6g, Fried ground beetle 5g, Prepared myrrh 3g, Prepared frankincense 3g, Prepared arisaema 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Mentha haplocalyx 9g, Trichosanthes kirilowii 10g, Prunus persica 10g, Safflower 10g;

[0182] Obtain the petrolatum base and heat and stir the base until completely melted; after the base cools to 65-70℃, add the raw drug powder to the base and stir evenly to obtain an ointment;

[0183] Then the paste is filled and labeled.

[0184] In this comparative example of a heat-clearing, swelling-reducing, and blood-stasis-removing ointment, peach kernel and safflower are added to the original ingredients.

[0185] The formula is suitable for chronic injuries, bruises, and severe cases of blood stasis such as arthralgia. However, for acute cases or those with intense heat and toxicity, its excessive blood-breaking power may worsen local capillary bleeding, thus hindering initial swelling reduction. This demonstrates that the basic formula in this application achieves an optimal balance between clearing heat and resolving blood stasis, making it suitable for a wider range of patients with acute injuries.

[0186] Comparative Example 6

[0187] Treatment was administered using diclofenac diethylamine emulsion (DV) manufactured by Novartis Pharmaceuticals Co., Ltd. in Beijing, serving as a positive control group.

[0188] The characteristics of each formulation in Examples 1-7 and Comparative Examples 1-6 are summarized below, as shown in Table 1:

[0189] Table 1. Comparison of the characteristics of external medicine compositions for clearing heat, reducing swelling, and removing blood stasis.

[0190]

[0191] To verify the efficacy of the topical medication compositions for clearing heat, reducing swelling, and removing blood stasis in the above embodiments and comparative examples, the applicant conducted a systematic animal experimental study. An acute ankle sprain model was established using C57BL / 6 mice. The mice were divided into groups including a normal control group, a model group (no treatment after modeling), seven embodiment groups, and six comparative example groups (n=9 per group). The administration regimen was once daily for seven consecutive days. Detection points were day 3, day 7, and day 16. Ankle swelling (relative swelling, right / left side) was measured in all groups, and the ankle joint tissue was scored using HE staining (0-10 points).

[0192] To verify the efficacy and safety of the topical medicine composition for clearing heat, reducing swelling and removing blood stasis in the acute phase of ankle sprain, we also performed safranin O-fast green staining on the normal control group, model group, Example 2 group and Comparative Example 6 group (diclofenac group) on days 3, 7 and 16 to observe the pathological changes of ankle joint tissue. In addition, we combined ELISA and Western blot detection to detect the expression of IL-1β and NF-κB p65, and clarified the efficacy and possible mechanism of action of different medication methods.

[0193] Experimental materials

[0194] (I) Laboratory Animals

[0195] C57BL / 6 mice, standard grade, 135 mice in total, male, 18-22g.

[0196] (II) Experimental Drugs

[0197] Voltaren, 7 example control drugs and 5 comparative control drugs.

[0198] (III) Experimental Reagents

[0199] 4% paraformaldehyde, decalcification solution, dehydration and clearing reagent, hematoxylin-eosin staining kit, safranin O-fast green staining kit, neutral resin, protein extraction reagent, protein quantification reagent, BCA protein quantification kit, NF-κB p65 antibody, GAPDH antibody, secondary antibody, electrophoresis solution, transfer solution, blocking solution, developing solution, etc.

[0200] (iv) Experimental Instruments

[0201] ExcelsiorAS Automatic Dehydrator, Thermo Fisher Scientific:

[0202] Apdi HistoStar embedding machine, Thermo Fisher Scientific; Apdi HM340E paraffin microtome, Thermo Fisher Scientific.

[0203] KD-T1 plate spreader, Kedi Instrument Equipment Co., Ltd.; Axioscope 5 upright fluorescence microscope, Zeiss AG, Germany; NanoDropONE ultra-micro spectrophotometer, Thermo Fisher Scientific, Inc.; Thermo Micro 21R high-speed refrigerated centrifuge, Thermo Fisher Scientific, Inc.; 1658033 miniature vertical electrophoresis system, Bio-Rad Laboratories, Inc., USA; ChemiScope 6200Touch chemiluminescence imager, Shanghai Qinxiang Scientific Instruments Co., Ltd.

[0204] Experimental methods

[0205] (I) Animal grouping, modeling and drug administration

[0206] After 7 days of acclimatization, 135 C57BL / 6 mice were randomly divided into 15 groups of 9 mice each: normal control group, model group (no treatment after modeling), 7 example groups, and 6 comparative groups.

[0207] An acute ankle sprain model was established using a mechanical injury method. The normal control group received only anesthesia and immobilization, without any applied force. Mice in the other groups were anesthetized via intraperitoneal injection, and their hind limbs were immobilized. The right hind foot was then inverted (inversion) and flexed downwards (plantar flexion) to a specific angle (e.g., 180°) at a certain frequency (e.g., 100 times / minute) for a period of time (e.g., 4 minutes). Subsequently, a self-made cylinder was positioned over the mouse's right hind ankle joint, and a 400g metal block was dropped vertically from a height of 10cm inside the cylinder to impact the joint. No fractures or dislocations were observed upon palpation.

[0208] After successful modeling, the model group mice were not given any drugs. The mice in the topical drug composition groups of the examples and comparative examples were treated with the corresponding drugs evenly applied to the ankle joints and covered with infusion patches after modeling, once a day for 7 consecutive days. No drug administration was performed from day 8 to day 16.

[0209] (II) Detection Indicators and Methods

[0210] 1. Weight measurement

[0211] After the experiment began, the mice were weighed and the data were recorded on the first and last days of the experiment to analyze the changes in mouse weight.

[0212] 2. Observation and measurement of ankle joint swelling in mice

[0213] After the experiment on days 3, 7, and 16, the swelling morphology of the right ankle of all groups of mice was observed, and the ankle thickness at the level of the line connecting the medial and lateral malleoli of each mouse was measured using vernier calipers. See [link to relevant documentation]. Figure 2 The right / left ratio reflects the relative swelling of the right ankle. Photos of the right ankle were taken on days 3, 7, and 16 of treatment in mice from the normal control group, model group, Example 2 group, and Comparative Example 6 group (diclofenac group).

[0214] 3. HE staining for observation of ankle joint histology

[0215] On days 3, 7, and 16 after the experiment, all mice were anesthetized. The ankle joint was cut approximately 0.3 cm above and below the tip of the right lateral malleolus. The skin, muscles, tendons, and other tissues of the joint were removed, and the right hind foot ankle joint was excised. Excess tissue was removed, and other tissues were washed in PBS solution and placed in 4% fixative. The soft tissue on the lateral side of the ankle joint was partially transferred to cryovials after washing, flash-frozen in liquid nitrogen, and stored at -80°C for later use.

[0216] Ankle joint tissue specimens were fixed in 10% neutral formalin for 24 hours and then decalcified with EDTA decalcification solution (pH 7.2) for 2 weeks until the acupuncture needle could penetrate the bone tissue with slight resistance. Afterward, the decalcified femoral samples were dehydrated, embedded in paraffin, and cut into 5µm thick sections. Hematoxylin and eosin (H&E) staining was performed, including dewaxing and hydration, hematoxylin staining of the nuclei, differentiation, blue staining, eosin staining of the cytoplasm, dehydration, clearing, and air drying. The sections were then mounted with functional resin and dried. The prepared HE-stained sections were observed under an optical microscope to examine pathological changes in the ankle joint tissue, such as inflammatory cell infiltration, tissue edema, and ligament damage repair, and semi-quantitative analysis was performed.

[0217] The following criteria were used to evaluate joint pathology slides using a blinded method:

[0218] Table 2 Pathological Scoring Criteria

[0219]

[0220] 4. Safranin O-Fixed Green staining for observation of ankle joint tissue morphology

[0221] Ankle joint sections from mice in the normal control group, model group, Example 2 group, and Comparative Example 6 group (diclofenac group) were dewaxed and placed in water. Hematoxylin staining was performed for 7 min, followed by rinsing with running water for 10 min, 0.5% Fast Green staining for 8 min, rinsing with 1% acetic acid for 15 s, 0.1% Safranin O staining for 5 min, and staining with 95% ethanol, anhydrous ethanol, and xylene for 2 min each. After drying, the sections were mounted. The prepared stained sections were observed under an optical microscope to examine the pathological changes in the ankle joint tissue. Cartilage appeared red, with hypertrophic chondrocytes showing deeper staining; cortical bone appeared green, and woven bone appeared purplish-red.

[0222] 5. Serum IL-1β level measurement

[0223] After the experiment concluded on days 3, 7, and 16, whole blood was collected from mice in the normal control group, model group, Example 2 group, and Comparative Example 6 group (diclofenac group). The blood was allowed to stand for 2 hours, centrifuged at 3000 rpm for 10 minutes, and serum was collected and stored at -20℃ for later use. IL-1β levels were determined according to the kit instructions. IL-1β concentrations were calculated after measuring the optical density of the samples using an ELISA reader.

[0224] 6. Western blot method for detecting NF-κB protein expression.

[0225] The expression level of NF-κB protein in the ankle joint specimens of four groups of mice, namely the normal control group, the model group, the Example 2 group, and the Comparative Example 6 group (diclofenac group), was detected by Western blot.

[0226] (1) Protein extraction: Take an appropriate volume of lysis buffer and mix it with 1% PMSF. For each sample, add the corresponding volume of lysis buffer at a ratio of 1:100 (m:V) according to the obtained mass, and place it on ice for lysis for 5 min. Centrifuge at 4℃, 12000 rpm for 10 min, and pipette the supernatant to obtain the protein extract.

[0227] (2) Protein concentration determination: The protein concentration of each sample was determined using an ultra-micro spectrophotometer.

[0228] (3) Polyacrylamide gel electrophoresis (SDS-PAGE): Protein samples were denatured at 95℃ for 5 min and a loading solution was prepared for later use. The sample was loaded (10 μL, containing 20 μg of protein). 2 μL of protein marker was added to the adjacent wells of the edge samples. The electrophoresis conditions were adjusted to 200V and constant voltage electrophoresis was performed for 35 min.

[0229] (4) Transfer: Cut a 5x6cm piece 2 The PVDF membrane was injected with sufficient transfer buffer, the electrode was turned on, the transfer conditions were adjusted, and the current was 400mA for 35 minutes for transfer.

[0230] (5) Sealing: Immerse the PVDF membrane in a rapid sealing solution for 30 minutes.

[0231] (6) Incubation of primary antibody: Prepare antibody working solution by diluting the antibody with TBST buffer containing 5% (m:V) skim milk powder. Place the solution in a sealed PVDF membrane and incubate overnight at 4°C.

[0232] (7) Secondary antibody incubation: After incubation with the primary antibody, remove the PVDF membrane from the hybridization bag and immerse it in TBST. Shake for 5 minutes, repeating this step 3 times. Dilute the antibody with 5% (m:V) skim milk powder TBST buffer to prepare the secondary antibody working solution. Place the rinsed PVDF membrane in the solution, seal it with a film press, and incubate at room temperature for 2 hours. (8) ECL substrate chemiluminescence: Remove the PVDF membrane, immerse it in TBST, and develop and photograph it in a developing instrument. Analyze the gray values ​​of the protein bands using ImageJ software, with GAPDH as an internal control.

[0233] 7. Statistical Analysis of Experimental Results

[0234] Statistical software was used to analyze the experimental data. Quantitative data were expressed as mean ± standard deviation. ±S) indicates that one-way ANOVA was used for comparisons among multiple groups. If the difference was statistically significant, pairwise comparisons between groups were then performed. A p-value < 0.05 was considered statistically significant.

[0235] Experimental results

[0236] (I) Effects on mouse weight gain rate

[0237] Seven days after administration, the weight gain rate in the model group was significantly lower than that in the normal group (P < 0.01). The weight gain rate in the treated group showed an increasing trend compared to the model group. See also Figure 3 .

[0238] Note: In the experimental report, compared with the normal group, ##P<0.01. CT: normal group; MD: model group; FT: diclofenac sodium group; HY: topical medicine combination group for clearing heat, reducing swelling and removing blood stasis.

[0239] In the experiments of this application, the P-value is used to determine whether the experimental result is caused by random factors.

[0240] P < 0.01 means that the probability that the observed difference (such as drug effect) is not accidental is less than 1%, indicating that the difference is very significant and the experimental results are reliable.

[0241] In the chart annotations, symbols are typically used to mark the significance of different levels:

[0242] P < 0.05: Significant difference (random probability < 5%)

[0243] P < 0.01: The difference is highly significant (random probability < 1%).

[0244] In lab reports or statistical charts, "#P" is usually a special notation used to indicate a significant difference compared to a specific control group. Its meaning is similar to the more common "#P". Similar to "P", but different symbols are used to distinguish different comparison groups.

[0245] #P<0.05 and ##P<0.01 indicate significance compared to other specific groups (such as another drug group or time point).

[0246] (II) Effect on ankle swelling in mice

[0247] See Figure 4 and Figure 5 Three days after administration, compared with the normal group, the swelling of the right ankle joint in the model group was significantly increased (P<0.05). Seven days after administration, compared with the normal group, the swelling of the right ankle joint in the model group was significantly increased (P<0.01); compared with the model group, the swelling of the right ankle joint in the diclofenac group was significantly decreased (P<0.01). Sixteen days after administration, compared with the normal group, the swelling of the right ankle joint in the model group was significantly increased (P<0.01); compared with the model group, the swelling of the right ankle joint in the diclofenac group and the topical medication combination group (which clears heat, reduces swelling, and removes blood stasis) was significantly decreased (P<0.01).

[0248] Note: In this experiment, compared with the normal group, P < 0.01. Compared with the model group, P<0.05, P<0.01. CT: normal group; MD: model group; FT: diclofenac group; HY: topical medicine combination group for clearing heat, reducing swelling and removing blood stasis.

[0249] (III) Effects on mouse serum IL-1β

[0250] See Figure 6Three days after administration, compared with the normal group, the serum IL-1β level in the model group was significantly increased (P<0.05); compared with the model group, the serum IL-1β level in the diclofenac group and the topical medicine combination group for clearing heat, reducing swelling, and removing blood stasis was significantly decreased (P<0.01). Seven days after administration, the serum IL-1β level in the model group was significantly increased (P<0.01); compared with the model group, the serum IL-1β level in the diclofenac group was significantly decreased (P<0.01). Compared with the normal group, the serum IL-1β level in the model group was significantly increased (P<0.05); compared with the model group, the serum IL-1β level in the diclofenac group and the topical medicine combination group for clearing heat, reducing swelling, and removing blood stasis was significantly decreased (P<0.01, P<0.05).

[0251] Note: In this experiment, compared with the normal group, #P<0.05, ##P<0.01. Compared with the model group, P<0.05, P<0.01. CT: Normal group: MD: Model group: FT: Diclofenac group; HY: Topical medicine combination group for clearing heat, reducing swelling and removing blood stasis.

[0252] (iv) Effects on HE staining of mouse ankle joint tissue

[0253] HE staining results are as follows Figure 7 As shown, the pathology scoring results are as follows: Figure 8 The normal group mice showed clear articular cartilage structure, smooth surface, orderly cell arrangement, and no inflammatory cell infiltration. The model group mice showed rough articular cartilage surface, irregular cell arrangement, significant tissue thickening, and the presence of inflammatory cells; the pathological score was significantly higher than the normal group (P<0.01). Compared with the model group, the diclofenac group and the topical medication combination group showed reduced synovial tissue pathological damage, improved synovial tissue hyperplasia and thickening, improved cell morphology, reduced inflammatory cell infiltration, and significantly lower pathological scores (P<0.05).

[0254] Note: In this experiment, compared with the normal group, #P<0.05, ##P<0.01. Compared with the model group, P<0.05, P<0.01. CT: normal group; MD: model group; FT: diclofenac group; HY: topical medicine combination group for clearing heat, reducing swelling and removing blood stasis.

[0255] (v) Effects on Safranin-Fix-Green staining of mouse ankle cartilage tissue

[0256] Safranin binds to polysaccharides in the cartilage matrix, turning it bright red, while Fast Green binds to collagen fibers on the cartilage surface and in the subchondral bone, turning it blue-green. In the normal group, the cartilage matrix was bright red and evenly distributed, the articular cartilage was of uniform thickness, and the boundary between the cartilage and subchondral bone was clear. In the model group, the cartilage surface was rough, the safranin staining in the cartilage matrix was lighter than in the control group, the articular cartilage was uneven in thickness, chondrocytes were disordered, the number of chondrocytes was significantly reduced, and the cartilage matrix was almost unstained; see also Figure 9 Compared with the model group, the cartilage surface of the diclofenac group and the topical medicine combination group for clearing heat, reducing swelling and removing blood stasis was smoother, the degree of safranin staining was increased, the degree of fast green staining was decreased, the morphology and structure were between the blank group and the model group, and the boundary between cartilage and subchondral bone was clearer.

[0257] (vi) Effects on the expression level of NF-κB p65 protein in the ankle joint of mice

[0258] The NF-κB p65 protein levels in the model group, diclofenac group, and the topical medication combination group (for clearing heat, reducing swelling, and removing blood stasis) were statistically significantly different from those in the blank control group (P<0.01, P<0.05). See also Figure 10 , Figure 11 After 3 and 7 days of medication, compared with the control group, the NF-κB p65 protein level in the model group was significantly increased (P<0.01, P<0.05). Compared with the model group, the NF-κB p65 protein level in both the diclofenac group and the topical medicine combination group for clearing heat, reducing swelling and removing blood stasis decreased after administration, and the differences were statistically significant (P<0.01, P<0.05).

[0259] In this experiment, compared with the normal group, #P<0.05 and ##P<0.01. Compared with the model group, P<0.05, P<0.01. CT: normal group; MD: model group; FT: diclofenac group; HY: topical medicine combination group for clearing heat, reducing swelling and removing blood stasis.

[0260] IV. Experimental Conclusions

[0261] Table 3: Summary of ankle swelling and pathological scores in mice on days 3 and 7 after administration in Examples 1-7 and Comparative Examples 1-6.

[0262]

[0263] Note: Compared with the model group, P<0.05, P<0.01.

[0264] As shown in Table 3, all example groups exhibited significant anti-swelling and tissue repair effects (P<0.05 or P<0.01 compared to the model group). Among them, Example 3 (high dose) showed the strongest effect, with ankle swelling and pathological scores approaching those of the normal group. Examples 4-6, through personalized adjustments, demonstrated excellent performance in specific aspects (such as blood stasis removal or heat clearing), supporting the scientific basis of the formula adjustment, and all showed certain heat-clearing and blood stasis removal effects. Example 7 (sesame oil base) used simple and natural ingredients, and sesame oil itself has moisturizing and detoxifying effects, with acceptable results.

[0265] The comparative groups all showed worse results than the basic formula (Example 1). Comparative Example 1 (without peppermint) and Comparative Example 2 (without peppermint and Phellodendron bark) showed reduced heat-clearing ability and higher inflammatory markers; Comparative Example 3 (without borneol) and Comparative Example 4 (without Panax notoginseng) showed decreased blood-stasis-removing effect; Comparative Example 5 (with added peach kernel and safflower) actually aggravated swelling, confirming that it is not suitable for the acute phase.

[0266] The results of this experiment indicate that the topical medication composition for clearing heat, reducing swelling, and removing blood stasis has a significant therapeutic effect on acute ankle sprains. Its core mechanism lies in effectively downregulating the expression of the downstream inflammatory factor IL-1β by inhibiting the activation of the NF-κB signaling pathway, thereby reducing joint inflammation and tissue damage. Histological evidence further confirms that the drug treatment can significantly improve pathological changes such as synovial hyperplasia and inflammatory cell infiltration, and promote cartilage matrix repair. The topical medication composition for clearing heat, reducing swelling, and removing blood stasis exhibits a long-lasting effect, showing better tissue repair function in the later stages of injury.

[0267] The topical medicine composition for clearing heat, reducing swelling, and removing blood stasis exhibits a sustained and enhanced therapeutic effect in the later stages of injury, a characteristic that gives it a unique advantage in the recovery phase of acute injury. This study validates the therapeutic efficacy of the topical medicine composition for clearing heat, reducing swelling, and removing blood stasis at multiple levels, from molecular mechanisms to histomorphology. This not only provides a scientific basis for its clinical application but also reflects the multi-component, multi-target, and holistic regulatory characteristics of traditional Chinese medicine.

[0268] This application also collected clinical application data on the use of this topical medicine composition for clearing heat, reducing swelling, and removing blood stasis, as follows:

[0269] Clinical application data

[0270] I. Objects and Methods

[0271] 1. Clinical Data

[0272] (1) Data Source: A retrospective study was conducted on 90 patients with acute ankle sprains who visited the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine between January 1, 2024 and December 31, 2024. Patients were divided into a control group and an observation group based on their treatment methods. The observation group consisted of 45 patients (21 males and 24 females), aged 22–60 years, with a disease duration of 6–18 (11.33±3.27) h. The control group consisted of 45 patients (22 males and 23 females), aged 21–60 years, with a disease duration of 6–17 (11.20±3.19) h. There were no statistically significant differences between the two groups (P>0.05).

[0273] (2) Diagnostic criteria for acute ankle sprain (based on the "Standards for Diagnosis and Efficacy of Diseases in Traditional Chinese Medicine"): ① A clear history of ankle injury; ② Pain, local swelling, subcutaneous ecchymosis, and limping immediately after injury; ③ Significant local tenderness; if it is an inversion sprain, there will be severe pain in the lower front of the lateral malleolus when the foot is inverted; if it is an eversion sprain, there will be severe pain in the lower front of the medial malleolus when the foot is everted; ④ No fracture is seen on X-ray or CT scan. A diagnosis can be made if ①-④ are met.

[0274] (3) Inclusion criteria: ① Meets the diagnostic criteria for acute ankle sprain; ② Age 18-60 years; ③ Acute patients whose time of visit to the doctor is less than 24 hours after the injury; ④ Have not received any treatment after the injury; ⑤ Complete clinical data including patient age, gender, course of disease, treatment method, treatment time and evaluation of treatment effect.

[0275] (4) Exclusion criteria: ① Patients with other lower limb injuries; ② Patients with a history of chronic ankle instability and recurrent sprains; ③ Patients who are allergic to the drugs used in this study, or whose local skin is broken and not suitable for external application; ④ Patients with a history of severe cardiovascular and cerebrovascular diseases, gastrointestinal ulcers, coagulation dysfunction, liver and kidney dysfunction, etc.; ⑤ Patients with mental illness who cannot cooperate with the treatment; pregnant women.

[0276] 2. Method

[0277] Both groups of patients followed the RICE principle: Rest, Cold, Compression, and Elevation. Based on the RICE principle, patients with acute ankle sprains received external ankle brace immobilization for 2 weeks, intermittent ice application (15-20 minutes every 2 hours within 48 hours), and the affected lower limb was elevated 30°. For the first 3 days after injury, the focus was on rest, limb elevation, and active toe movement. After 3 days, safe activities could begin, with partial weight-bearing on the affected ankle. If pain was unbearable, crutches were used to assist walking.

[0278] The control group was given diclofenac diethylamine emulsion (Beijing Novartis Pharmaceutical Co., Ltd.) applied to the affected area, gently massaged to allow the drug to penetrate the skin, once in the morning, noon and evening, with an interval of 6-8 hours between each application, for 7 consecutive days.

[0279] The observation group was given the topical medicine composition of the present invention for clearing heat, reducing swelling, and removing blood stasis. The composition of the medicine is as follows:

[0280] Raw Phellodendron bark 6g, Borneol 3g, Red peony root 10g, Prepared frankincense 3g, Prepared myrrh 3g, Fried ground beetle 5g, Panax notoginseng slices 6g, Prepared arisaema 6g, Liquidambar formosana 10g, Angelica dahurica 10g, Mentha haplocalyx 9g, Trichosanthes kirilowii 10g. Administer every 4-6 hours, once daily, for 7 consecutive days.

[0281] Preparation method: Grind the above-mentioned Chinese herbal medicine slices into a fine powder of 100-150 mesh. Then heat petroleum jelly until completely melted. When the petroleum jelly cools to 70℃, pour in the fine powder and stir well to form a paste. Take an appropriate amount and apply it to the affected ankle with sterile gauze. During the acute phase, place ice cubes on top of the ointment through the gauze to treat the affected area. During the 4-6 hour period of application, apply ice multiple times, 15-20 minutes each time.

[0282] 3. Observation indicators

[0283] (1) Clinical efficacy evaluation criteria: The clinical efficacy evaluation criteria were formulated with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial Implementation)". Cure: Swelling and pain in the ankle joint completely subsided, and ankle joint movement was normal. Marked effect: Swelling and pain in the ankle joint basically subsided, and ankle joint movement was not restricted. Effective: Slight ecchymosis or swelling remained on the skin surface of the ankle joint, pain symptoms were somewhat reduced, and ankle joint movement improved. Ineffective: There was no significant improvement in ankle pain and swelling, and no change in ankle joint movement. Total effective rate (%) = (Number of cured cases + Number of markedly effective cases + Number of effective cases) / Total number of cases X100%. Evaluations were conducted at 3, 7, and 16 days after treatment.

[0284] (2) Ankle pain severity: The visual analogue scale (VAS) was used to assess ankle pain before treatment and at 3, 7, and 16 days after treatment. The score ranged from 0 to 10, with 0 representing no pain and 10 representing the most painful. Below 3: Mild pain that is tolerable; 4-6: Pain that affects sleep; 7-10: Severe pain that is unbearable and affects appetite and sleep.

[0285] (3) Ankle joint function: The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was used, including multiple aspects such as pain, function, voluntary movement and support, maximum walking distance, ground walking, paradoxical gait, forefoot and hindfoot movement, hindfoot movement, ankle-hindfoot stability, and foot alignment, with a total score of 100 points. The score was completed by the physician based on the patient's actual condition; a lower score indicated more limited ankle joint function. Assessments were conducted before treatment and at 3, 7, and 16 days after treatment.

[0286] (4) Quantitative assessment of ankle swelling: Based on the quantitative standards for injury grading in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine (Trial Implementation)" (using a scale method and comparing with the healthy side), the specific scoring standards are as follows: no swelling is scored as 1 point; slight swelling, with the center of swelling less than 0.5 cm high, is scored as 2 points; moderate swelling, with the center of swelling between 0.5-1 cm high, is scored as 3 points; and severe swelling, with the center of swelling exceeding 1 cm high, is scored as 4 points; the higher the score, the more severe the swelling. Assessments were conducted before treatment and at 3, 7, and 16 days after treatment.

[0287] 4. Statistical methods used SPSS 26.0 statistical software.

[0288] Quantitative data are expressed as mean ± standard deviation ( ±S) indicates the mean, and the t-test or rank-sum test is used for comparisons between groups: the results of count data are expressed as n (%).

[0289] II. Research Results

[0290] 1. Comparison of clinical efficacy between the two groups

[0291] Table 4 shows the results: After 7 days of treatment, the total effective rate in the experimental group was 95.56% (43 / 45), while that in the control group was 88.89% (40 / 45). The difference between the groups was statistically significant (χ²). 2 The results showed that the therapeutic effect of the experimental group was significantly better than that of the control group (P<0.05).

[0292] Table 4. Comparison of clinical efficacy between the two groups of subjects.

[0293]

[0294] 2. Comparison of ankle pain levels between the two groups

[0295] After paired-samples rank-sum test, the changes in VAS scores before and after treatment were significant in both groups. Specifically, within-group comparisons showed Z1=-4.806 for the experimental group and Z2=-4.808 for the control group, with P values ​​less than 0.05 for both groups. This strongly indicates that pain symptoms were significantly reduced in both groups after treatment. Further analysis of the differences in efficacy between the two groups revealed statistically significant differences in pain relief between the two groups on days 3 and 7 of treatment (P<0.05), meaning the experimental group showed a more significant pain relief effect. However, by day 16 of treatment, there was no significant difference in pain relief between the two groups (P>0.05), indicating that after two weeks of treatment, the pain relief status of the experimental and control groups was essentially consistent (see Table 5).

[0296] Table 5. VAS scores of the two groups of subjects before and after treatment.

[0297]

[0298] 3. Comparison of ankle joint mobility between the two groups

[0299] Within-group comparisons of AOFAS scores before and after treatment showed that, after paired-samples rank-sum test, the experimental group Z=-4.789, P<0.05, while the control group t=-34.291, P<0.05, indicating a statistically significant difference. This suggests that the AOFAS scores of both groups increased significantly after treatment. Between-group comparisons showed P<0.05, indicating a significant difference between the two groups, with the experimental group having a higher AOFAS score than the control group, suggesting that the experimental group was more effective in improving ankle joint function (see Table 6).

[0300] Table 6. AOFAS scores of the two groups of subjects before and after treatment

[0301]

[0302] 4. Quantitative assessment and comparison of the degree of ankle swelling between the two groups

[0303] Table 6 shows that before treatment, there was no statistically significant difference in ankle swelling scores between the two groups (P>0.05), indicating comparability. After treatment, the ankle swelling scores in both groups were significantly lower than before treatment (P<0.05), and the experimental group showed a significantly greater reduction in ankle swelling scores than the control group, with statistically significant differences (P<0.05 or P<0.01). (See Table 7)

[0304] Table 7. Quantitative assessment of ankle swelling before and after treatment in both groups of subjects.

[0305]

[0306] In the description of this specification, the terms "one embodiment," "some embodiments," "a specific implementation," "a particular implementation," "other implementations," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment, implementation, or example of the present invention. In this specification, the 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 above can also be combined in any suitable manner in one or more embodiments, implementations, or examples. The technical solutions described in this invention also include technical solutions formed by any one or more specific features, structures, materials, or characteristics described above, either individually or in combination.

[0307] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions, alterations, deletions of some features, additions of features, or recombinations of features to the above embodiments within the scope of the present invention without departing from the principles and spirit of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the innovative principles of the present invention shall still fall within the scope of the technical solutions of the present invention.

Claims

1. A topical medication composition for the acute phase of clearing heat, reducing swelling, and removing blood stasis, characterized in that, It is composed of the following raw medicinal materials in parts by weight: 5-8 parts raw Phellodendron bark, 2-5 parts borneol, 8-12 parts red peony root, 4-8 parts Panax notoginseng, 4-6 parts stir-fried ground beetle, 2-4 parts processed myrrh, 2-4 parts processed frankincense, 5-8 parts processed Arisaema, 8-12 parts Liquidambar formosana, 8-12 parts Angelica dahurica, 8-12 parts peppermint, and 8-12 parts Trichosanthes kirilowii.

2. The topical medication composition for clearing heat, reducing swelling, and removing blood stasis in the acute phase according to claim 1, characterized in that, It is composed of the following raw pharmaceutical ingredients in parts by weight: 6-8 parts of raw Phellodendron bark, 3-5 parts of borneol, 10-12 parts of red peony root, 6-8 parts of Panax notoginseng, 5-6 parts of stir-fried ground beetle, 3-4 parts of processed myrrh, 3-4 parts of processed frankincense, 6-8 parts of processed Arisaema heterophyllum, 10-12 parts of Liquidambar formosana, 10-12 parts of Angelica dahurica, 9-12 parts of peppermint, and 10-12 parts of Trichosanthes kirilowii.

3. The topical medication composition for clearing heat, reducing swelling, and removing blood stasis in the acute phase according to claim 2, characterized in that, It is composed of the following raw medicinal ingredients in parts by weight: 6 parts raw Phellodendron bark, 3 parts borneol, 10 parts red peony root, 3 parts prepared frankincense, 3 parts prepared myrrh, 5 parts stir-fried ground beetle, 6 parts Panax notoginseng, 6 parts prepared Arisaema heterophyllum, 10 parts Liquidambar formosana, 10 parts Angelica dahurica, 9 parts peppermint, and 10 parts Trichosanthes kirilowii.

4. The topical medication composition for clearing heat, reducing swelling, and removing blood stasis in the acute phase according to claim 1, characterized in that, It is composed of the following raw pharmaceutical ingredients in parts by weight: 5-8 parts of raw Phellodendron bark, 5 parts of borneol, 10-12 parts of red peony root, 3-4 parts of processed frankincense, 3-4 parts of processed myrrh, 5-6 parts of stir-fried ground beetle, 4-6 parts of Panax notoginseng, 5-6 parts of processed Arisaema heterophyllum, 10-12 parts of Liquidambar formosana, 10-12 parts of Angelica dahurica, 12 parts of peppermint, and 10-12 parts of Trichosanthes kirilowii.

5. The topical medication composition for clearing heat, reducing swelling, and removing blood stasis in the acute phase according to claim 4, characterized in that, It is composed of the following raw material components in parts by weight: 5 parts raw Phellodendron bark, 5 parts borneol, 12 parts red peony root, 3 parts prepared frankincense, 4 parts prepared myrrh, 6 parts stir-fried ground beetle, 6 parts Panax notoginseng, 5 parts prepared Arisaema heterophyllum, 12 parts Liquidambar formosana, 12 parts Angelica dahurica, 12 parts peppermint, and 12 parts Trichosanthes kirilowii.

6. The topical medication composition for clearing heat, reducing swelling, and removing blood stasis in the acute phase according to claim 1, characterized in that, The acute-phase topical medication composition is in the form of a spray, a water-based solution, a gel, a liniment, an ointment, a plaster, or other pharmaceutically acceptable topical dosage form.

7. Use of the acute-phase topical medicament composition according to any one of claims 1-6 in the preparation of a medicament for treating acute-phase injuries.

8. The application according to claim 7, characterized in that, During the acute phase of injury, the aforementioned acute-phase topical medication composition was used in accordance with the RICE principle.

9. In the application according to claim 8, during the acute phase injury, the treatment with the acute phase topical medication composition and the ice application step are performed simultaneously; during the non-acute phase injury, the acute phase topical medication composition is applied as a hot compress to the affected area at a temperature of 40°C-50°C.

10. A method for preparing an acute-phase topical medicine composition for clearing heat, reducing swelling, and removing blood stasis, characterized in that: For use in preparing the topical ointment of the acute phase drug composition as described in any one of claims 1-5; The method includes the following steps: Obtain the matrix, and heat and stir the matrix until it is completely melted; Obtain the active pharmaceutical ingredient according to the specified ratio, and grind the active pharmaceutical ingredient into powder; Once the matrix has cooled to 65-70℃, add the raw drug powder to the matrix and stir evenly to obtain a paste.

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