Traditional Chinese medicine patch for treating subcutaneous ecchymosis as well as preparation method and application of traditional Chinese medicine patch

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a traditional Chinese medicine patch for treating subcutaneous ecchymosis and a preparation method and application thereof. The traditional Chinese medicine patch is prepared from medicine components and medicine-carrying gel, the medicine components are prepared from cortex moutan, radix paeoniae rubra and mirabilite, and the medicine-carrying gel is prepared from components in percentage by mass as follows: 30%-40% of a styrene-isoprene-styrene block copolymer, 19%-24% of a tackifier, 35%-40% of a softener, 4%-7% of inorganic salt and 0.1%-2% of sodium polyacrylate. The mass content of isoprene in the styrene-isoprene-styrene block copolymer is 65 to 80 percent. The traditional Chinese medicine composition has the advantages of no allergy, no stimulation, good heat resistance and shaping property, remarkable curative effect on subcutaneous ecchymosis and good pain relieving effect.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, specifically to a traditional Chinese medicine plaster for treating subcutaneous ecchymosis, its preparation method, and its uses. Background Technology

[0002] Subcutaneous ecchymosis is caused by damage to capillaries, veins, or arteries due to various reasons, or by disorders of the blood clotting system, such as thrombocytopenia, resulting in blood remaining in tissues outside the blood vessels. Common causes include various traumas, and procedures such as intravenous infusions, blood draws, and angiography can all cause subcutaneous ecchymosis and hematomas. Postoperative hematomas and ecchymoses can lead to local swelling and pain. The occurrence of subcutaneous ecchymosis and hematomas not only causes anxiety and tension in patients but also makes subsequent intravenous medication, blood collection, and punctures difficult, affecting treatment and even impacting early postoperative limb movement. Furthermore, it easily leads to bacterial growth and wound infection; if not treated promptly, it can cause serious complications such as compartment syndrome. The incidence of subcutaneous ecchymosis is high, especially after procedures involving significant vascular trauma, and larger ecchymoses are less likely to heal.

[0003] Currently, there is a lack of effective treatments for subcutaneous ecchymosis caused by various reasons. Generally, the natural absorption process is allowed. Clinically, interventions are only used for larger areas of subcutaneous ecchymosis, such as hot compresses, magnesium sulfate wet compresses, millimeter wave irradiation, and topical application of fresh aloe vera. Clinical data shows that the absorption of subcutaneous ecchymosis typically takes one week for mild cases and two to three weeks for severe cases. This significantly affects patients' emotions, prolongs hospital stays, and increases their psychological burden and hospitalization costs. Therefore, convenient and effective medications for treating subcutaneous ecchymosis are of great clinical significance.

[0004] In clinical practice, the commonly used external application method is wet compress, which involves thoroughly soaking a disposable compressed towel or sterile gauze in the medication and covering the ecchymosis or hematoma (avoiding puncture sites; puncture sites are covered and protected with sterile dressings). The coverage area extends more than 1 cm beyond the ecchymosis area. 2 -2cm 2 Then, wrap the outer layer with plastic wrap to prevent the medicine from staining clothes and the moisture in the medicine from evaporating, which would greatly reduce the efficacy. After the intervention, the local skin also needs to be wiped with warm water to keep the skin clean and dry. Each application lasts for 4 hours, and it needs to be used twice a day for a total of 8 hours until the skin is healed, which brings a lot of inconvenience to clinical nursing.

[0005] Clinically, ointments / soft creams are often used to treat ecchymosis. These are made by mixing the medication with petroleum jelly as a base, creating an ointment / soft cream that is then applied directly and evenly to the ecchymotic area. To prevent the ointment from staining clothing or the medication from detaching from the ecchymotic area and affecting efficacy, the outer layer is usually manually wrapped with sterile gauze or plastic wrap. Alternatively, a polyurethane sponge can be soaked in the ointment / soft cream until saturated, then removed and adhered to the affected area with pressure-sensitive adhesive tape. The skin is cleaned after each treatment, and the treatment is repeated until healed. Because ointments / soft creams are used, the skin is more difficult to clean, requiring the use of cleansing agents, which adds inconvenience to clinical care. Furthermore, the more steps involved in the care process, the greater the risk of wound infection.

[0006] For example, Chinese Patent Publication No. CN101172129A discloses a traditional Chinese medicine composition for treating subcutaneous ecchymosis, which is made from the following raw materials in parts by weight: 1-5 parts by weight of peony bark, 1-5 parts by weight of red peony root, and 1-5 parts by weight of Glauber's salt. It also discloses that the above-mentioned wet compress method or soft / oil ointment can be used for treatment.

[0007] Neither wet compresses nor ointments can facilitate the widespread, standardized, and convenient clinical application of the products. Therefore, developing a traditional Chinese medicine patch for treating subcutaneous ecchymosis is essential. Currently, no patch for the aforementioned traditional Chinese medicine composition is publicly available.

[0008] The existing technology (Wang Zhonghua. Research progress on the mechanism of action and clinical application of traditional Chinese medicine plasters [J]. Hebei Journal of Traditional Chinese Medicine, 2017, 39(3):6.) discloses that some adverse reactions may occur in the clinical application of traditional Chinese medicine plasters. Mild reactions may include local skin redness, itching, burning and mild stinging. Severe reactions may include local skin redness, swelling, allergy, pain, blisters of various sizes, ulceration, and even low-grade fever.

[0009] For compound traditional Chinese medicine plasters, in addition to reducing allergies and irritation, it is also necessary to improve the release rate of each active ingredient while ensuring good adhesion, thereby enhancing the therapeutic effect of the plaster. To achieve rapid release of the active ingredients, the composition of the drug-loaded gel needs to be screened.

[0010] Therefore, it is essential to develop a traditional Chinese medicine plaster for treating subcutaneous ecchymosis that can solve the above-mentioned technical problems and its preparation method. Summary of the Invention

[0011] The purpose of this invention is to overcome the shortcomings of the prior art by providing a traditional Chinese medicine patch for treating subcutaneous ecchymosis, its preparation method, and its uses. This traditional Chinese medicine patch has excellent adhesion properties to the skin and has the effects of promoting microcirculation, inhibiting platelet and erythrocyte aggregation, promoting blood circulation and removing blood stasis, relieving pain, anti-inflammation, antibacterial, hemostasis, and reducing swelling. It can be directly applied to the affected area and has good efficacy, safety, and ease of use, making it convenient for clinical promotion and use.

[0012] Subcutaneous ecchymosis and hematoma, in Traditional Chinese Medicine (TCM), are considered to be caused by external injury leading to local stagnation of Qi and blood, resulting in blood stasis and swelling and pain in the limbs. TCM believes that if blood vessels are not flowing smoothly, blood that has escaped its proper channels and overflows under the skin will not dissipate, forming ecchymosis. Treatment focuses on promoting blood circulation and removing blood stasis. Modern medical research suggests that the skin acts as an entry point for medication. After topical administration, TCM herbs that promote blood circulation and remove blood stasis are transported through the skin and mucous membranes, absorbed by the skin's capillary network, and enter the bloodstream. Most of the medication directly reaches the application site to exert its effect, creating a relatively dominant drug concentration locally and accelerating the dissipation of ecchymosis. Compared with traditional methods of hematoma prevention and treatment, TCM herbs have the effects of clearing the meridians, promoting blood circulation, removing blood stasis, and relieving pain, as well as a unique holistic, multi-target mechanism of action and the advantages of simplicity, economy, and safety.

[0013] This invention is achieved through the following technical solutions: The first aspect of this invention provides a traditional Chinese medicine patch for treating subcutaneous ecchymosis, comprising a medicinal component and a drug-loaded gel. The raw materials of the medicinal component include peony bark, red peony root, and mirabilite. The drug-loaded gel, by weight percentage, comprises the following components: 30-40% styrene-isoprene-styrene block copolymer, 19-24% thickener, 35-40% softener, 4-7% inorganic salts, and 0.1-2% sodium polyacrylate.

[0014] In a preferred embodiment of the present invention, the drug-loaded gel comprises the following components by weight percentage: 36% styrene-isoprene-styrene block copolymer, 20% tackifier, 38% softener, 4.9% inorganic salts, and 1% sodium polyacrylate.

[0015] The drug-loaded gel of the present invention is used for drug loading and has pressure-sensitive adhesive properties. The styrene-isoprene-styrene block copolymer is used as the skeleton material, sodium polyacrylate is used as the adhesive polymer material, the softener has good compatibility with the above components, and inorganic salts are used as fillers to change the excipients.

[0016] The peony bark used in this invention is the dried root bark of the peony plant (Paeonia suffruticosa), a member of the Ranunculaceae family. The roots are harvested in autumn, the fine rootlets are removed, the root bark is peeled off, and then it is sun-dried. It is bitter, pungent, and slightly cold in nature. It enters the heart, liver, and kidney meridians, and has the effects of clearing heat and cooling blood, promoting blood circulation and removing blood stasis. One of its main active ingredients, paeonol, has various pharmacological effects, such as antipyretic, analgesic, anti-inflammatory, antibacterial, anti-allergic, immune-enhancing, sedative, and hypnotic properties. It can protect the cardiovascular system, resist arrhythmia, resist arteriosclerosis, improve microcirculation, and also has antibacterial effects and inhibits skin pigment synthesis, promoting local microcirculation.

[0017] The red peony root in this invention is the root of *Paeonia lactiflora* or *Paeonia veitchii*, both belonging to the Ranunculaceae family. It is bitter and slightly cold in nature, and enters the liver meridian. It has the effects of clearing heat and cooling blood, dispersing blood stasis and relieving pain. Its main active ingredients are paeoniflorin, paeoniflorin lactone, hydroxypaeoniflorin, benzoylpaeoniflorin, and other compounds, which possess a wide range of pharmacological activities, including inhibiting platelet and erythrocyte aggregation, anticoagulation and antithrombosis, anti-atherosclerosis, protecting the heart and liver, and anti-tumor activity. It is commonly used to treat febrile diseases with rashes, hematemesis and epistaxis, red and swollen eyes, liver stagnation and hypochondriac pain, amenorrhea and dysmenorrhea, abdominal masses and pain, traumatic injuries, carbuncles and sores. Red peony root can clear heat from the blood and disperse blood stasis. It invigorates blood, has a dispersing and purging nature, and excels in invigorating blood, dispersing blood stasis, and relieving pain.

[0018] The Glauber's salt in this invention is a crystalline form of Glauber's salt, a sulfate mineral belonging to the Glauber's salt group, refined through processing. It mainly contains hydrated sodium sulfate (Na₂SO₄·10H₂O). It has a salty and bitter taste, and is cold in nature. It enters the stomach and large intestine meridians, and is used as a purgative, possessing the effects of purging heat and promoting bowel movements, moistening dryness and softening hard masses, and clearing heat and reducing swelling.

[0019] In one embodiment of the present invention, the amount of the drug component is 2%-50% of the total mass of the drug component and the drug-loaded gel.

[0020] Preferably, the amount of the drug component is 10%-50% of the total mass of the drug component and the drug-loaded gel.

[0021] In one embodiment of the present invention, the raw materials of the medicinal components include, by weight, 1-10 parts of peony bark, 1-10 parts of red peony root, and 1-10 parts of Glauber's salt.

[0022] Preferably, the raw materials of the medicinal ingredients include, by weight, 2-6 parts of peony bark, 1-4 parts of red peony root, and 1-4 parts of Glauber's salt.

[0023] In this invention, the number-average molecular weight (Mn) of the styrene-isoprene-styrene block copolymer used as the backbone material is between 80,000 and 180,000. Choosing a styrene-isoprene-styrene block copolymer with this molecular weight provides appropriate cohesion. If the molecular weight (Mn) is below 80,000, the cohesion of the backbone material is relatively small, and the prepared patch is prone to problems such as glue seepage, glue overflow, and residue after use. If the molecular weight is above 180,000, the cohesion of the backbone material is relatively large, which will result in poor applicability and deterioration of the processing performance of the patch.

[0024] In this invention, the isoprene content of the styrene-isoprene-styrene block copolymer in the skeleton material is between 65% and 80%. When the isoprene content is too high, it will lead to low drug loading, poor cohesion, and even the problem of paste flow. When the isoprene content is too low, it will lead to poor processing performance.

[0025] The mass percentage of styrene-isoprene-styrene block copolymer in the drug-loaded gel is between 5% and 60%, such as 5%, 10%, 20%, 30%, 40%, 50%, and 60%, preferably between 5% and 45%. When the mass percentage is less than 5%, the cohesion of the drug-loaded gel becomes very poor, and the prepared patch adhesive layer is prone to problems such as breakage, glue rot, glue seepage, and glue overflow, and the drug loading is very small; when the mass percentage is greater than 60%, the cohesion of the drug-loaded gel is too large, and the processing performance deteriorates.

[0026] The tackifier of this invention mainly includes one or more of the following: rosin resin and its derivatives such as rosin glycerol ester, hydrogenated rosin, or hydrogenated rosin glycerol ester; C5 petroleum resin and its derivatives; C9 petroleum resin; terpene resins; polyisobutylene; polyurethanes; polyamides; epoxy resins; polyacrylic acids; and silicones. Preferably, it includes one or more of the following: rosin resin and its derivatives such as rosin glycerol ester and hydrogenated rosin; C5 petroleum resin and its derivatives; polyisobutylene; polyurethanes; polyacrylic acids; and silicones. More preferably, it includes one or more of the following: rosin resin and its derivatives such as rosin glycerol ester and hydrogenated rosin; medium molecular weight polyisobutylene with a molecular weight between 20,000 and 50,000; and high molecular weight polyisobutylene with a molecular weight between 50,000 and 200,000.

[0027] The tackifier has a mass percentage content in the drug-loaded gel between 0.01% and 60%, such as 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, and 60%, preferably between 19% and 24%. When the tackifier content is higher than 24%, its peeling force is too great, causing severe pain to the skin during peeling, severely damaging the epidermal structure, and also significantly damaging the cohesion of the drug-loaded gel, affecting its drug loading capacity. During use, there is glue overflow around the patch, and serious residue remains on the skin surface.

[0028] In one embodiment of the present invention, the softener includes one or more of naphthenic oil, polyisobutylene, liquid paraffin, olive oil, soybean oil and their derivatives.

[0029] As one embodiment of the present invention, the soybean oil derivative includes at least one of epoxidized soybean oil and hydrogenated soybean oil.

[0030] The softener of the present invention is preferably an oil-based substance that has good compatibility with the styrene-isoprene-styrene block copolymer as a backbone material and exhibits good thermo-oxidative stability between 130°C and 200°C, such as polyisobutylene, naphthenic oil, liquid paraffin, soybean oil and its derivatives such as epoxidized soybean oil and hydrogenated soybean oil, or one or more thereof. The polyisobutylene is preferably low molecular weight polyisobutylene with a molecular weight range of 100-1000, more preferably 400-800, and even more preferably 600.

[0031] The softening agent has a mass percentage content in the drug-loaded gel between 8% and 60%, such as 8%, 10%, 12%, 15%, 20%, 30%, 40%, 50%, and 60%, preferably between 12% and 50%. When the mass percentage content of the softening agent is within the above range, the drug-loaded gel has good cohesiveness and a good solubility effect on the styrene-isoprene-styrene matrix material. At the same time, the prepared drug-loaded gel has a low softening point and good processing performance at a lower temperature. The low softening point and good processing performance have a protective effect on the drug components during the product processing, especially for thermo-oxidative unstable or volatile drug components, which can greatly reduce the degree of oxidation or decomposition due to high temperature or reduce the volatilization of volatile drug components. If the mass percentage of the softener is less than 8%, the dissolution effect of the styrene-isoprene-styrene block copolymer backbone material deteriorates, the dissolution time increases significantly, and the structure of the backbone material is damaged. At the same time, the prepared drug-loaded gel has a high softening point, strong cohesion, and poor processability. Moreover, high temperature will destroy the drug nutrients, especially thermo- and oxygen-unstable or volatile drug nutrients, making it unsuitable for preparing patch preparations. When the mass percentage of the softener is greater than 60%, its cohesion deteriorates, the excipient properties of the drug-loaded gel deteriorate, and problems such as glue leakage, glue overflow, and skin residue are prone to occur.

[0032] In one embodiment of the present invention, the mass ratio of the styrene-isoprene-styrene block copolymer to the softener is 0.9-1.0:1. Within this mass ratio range, the patch exhibits superior heat resistance and shape retention.

[0033] As one embodiment of the present invention, the inorganic salts include, but are not limited to, at least one of calcium carbonate, titanium dioxide, zinc oxide and talc.

[0034] The drug-loaded gel of the present invention may also selectively add other special additives that improve its excipient properties, cohesion, and drug dispersion, such as inorganic salts including calcium carbonate, titanium dioxide, zinc oxide, or talc fillers, whose mass percentage in the drug-loaded gel is between 0.01% and 10%, for example, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, preferably between 0.01% and 7%.

[0035] The drug-loaded gel of the present invention may also optionally contain a certain amount of sodium polyacrylate to enhance the drug-loaded gel’s ability to absorb sweat. The amount added is between 0.01% and 10% by mass, such as 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, preferably between 0.01% and 7%.

[0036] In one embodiment of the present invention, the herbal patch further includes a backing cloth. The backing cloth serves to adhere the medicinal ingredients and the drug-carrying gel.

[0037] Preferably, the backing fabric is one of non-woven fabric, woven fabric, biaxial elastic fabric, uniaxial elastic fabric, and polyurethane film.

[0038] As one embodiment of the present invention, the thickness of the backing fabric is between 5μm and 1500μm, preferably between 100μm and 1000μm. Backing fabrics within the above thickness range can provide good support without appearing "heavy" and can also provide good skin adhesion.

[0039] Preferably, the herbal patch further includes a protective layer.

[0040] More preferably, the protective layer includes at least one of release paper and release film.

[0041] In one embodiment of the present invention, the release film is made of at least one of PET, PE, PP, PU, ​​and PC. The release film or release paper of the present invention can be single-sided or double-sided. The thickness of the protective layer is between 0.01mm and 0.5mm, preferably between 0.03mm and 0.3mm. Selecting a protective layer with a thickness within this range offers advantages in product manufacturing processes, providing good processability and sufficient support.

[0042] In one embodiment of the present invention, the total content of the drug components and the drug-loaded gel in the traditional Chinese medicine patch is 50 g / m². 2 -300g / m 2 Drug composition: drug-loaded gel = 2:98-50:50 (drug composition accounts for 2%-50% of the total mass of the drug and drug-loaded gel mixture).

[0043] Preferably, the total content of the drug components and drug-loaded gel in the traditional Chinese medicine patch is 100 g / m³. 2 -300g / m 2 Drug composition: drug-loaded gel = 10:90-50:50 (drug composition accounts for 10%-50% of the total mass of the drug and drug-loaded gel mixture).

[0044] A second aspect of the present invention provides a method for preparing the above-mentioned traditional Chinese medicine plaster, comprising the following steps: (1) Boil peony bark and red peony root in water, concentrate the decoction and add Glauber's salt to obtain the medicinal components; (2) After the drug-loaded gel is melted, it is mixed evenly with the drug components to obtain a gel-drug mixture; (3) Apply the adhesive mixture to the backing cloth and cover it with a protective layer to obtain the final product.

[0045] The medicinal components of this invention's herbal patch are a concentrated decoction of peony bark and red peony root, mixed with Glauber's salt to form a medicinal extract. Its drug-carrying matrix is ​​a drug-carrying gel with a styrene-isoprene-styrene block copolymer as the backbone material. The medicinal extract and the drug-carrying gel are uniformly mixed and adhered to a backing cloth under specific process conditions to prepare the herbal patch. It has the effects of promoting microcirculation, inhibiting platelet and erythrocyte aggregation, promoting blood circulation and removing blood stasis, relieving pain, anti-inflammation, antibacterial, hemostasis, and reducing swelling. It also features excellent application performance, no allergies, no irritation, no pain upon removal, reusability, and a large dosage.

[0046] As one embodiment of the present invention, the preparation method includes the following steps: (1) Weigh each drug ingredient raw material according to its weight parts; (2) Boil peony bark and red peony root in water, concentrate the decoction and add Glauber's salt to obtain the medicinal components; (3) Add the prepared drug components from (2) into a storage tank equipped with a precision metering pump (drug pump) for later use; (4) Add each component of the drug-loaded gel for preparing the patch to a melting tank equipped with a precision metering pump (glue pump). After each component is completely melted, the adhesive solution is obtained and set aside. (5) Turn on the coating machine and accurately pump the drug components and adhesive into the coating machine through the drug pump and adhesive pump respectively. Quickly and evenly mix the adhesive and drug components. The mixing time is generally between 20s and 80s. (6) Apply the mixed adhesive mixture evenly to the backing cloth according to a certain content standard and cover it with a protective layer, and then die-cut it into patches of a certain size.

[0047] In one embodiment of the present invention, in step (1), peony bark and red peony root are decocted with water 2-6 times.

[0048] In one embodiment of the present invention, in step (1), the peony bark and red peony root are decocted with 2-7 times their weight of water 4 times, each time for 30-120 minutes.

[0049] The third aspect of the present invention provides the use of the above-mentioned traditional Chinese medicine patch or the traditional Chinese medicine patch prepared by the above-mentioned preparation method in the preparation of a drug for treating subcutaneous ecchymosis.

[0050] As one embodiment of the present invention, the subcutaneous ecchymosis refers to the state in which blood remains in the subcutaneous tissue.

[0051] As one embodiment of the present invention, the subcutaneous ecchymosis refers to a condition in which blood remains in the subcutaneous tissue due to damage to capillaries, veins, or arteries caused by various traumas or vascular punctures; or due to blood clotting system disorders.

[0052] The method of using the herbal patch of this invention: The treatment cycle of the patch of this invention depends on the severity of the condition. The following method of use and course of treatment are for guidance: Apply the patch to the affected area of ​​ecchymosis, extending 1-2 cm beyond the area of ​​the ecchymosis. 2 Each treatment should last at least 4 hours, twice a day, for 3 days as one course of treatment, until the ecchymosis heals and disappears.

[0053] The beneficial effects of the present invention are: The herbal plaster of the present invention has the effects of promoting blood circulation, removing blood stasis, and reducing swelling. It can effectively treat subcutaneous ecchymosis caused by various reasons, that is, the state of blood remaining in the subcutaneous tissue. For example, blood remaining in the subcutaneous tissue is caused by damage to capillaries, veins, and arteries due to various traumas, vascular punctures, etc.; or blood remaining in the subcutaneous tissue is caused by disorders of the blood coagulation system. Detailed Implementation

[0054] The present invention will be further described below with reference to specific embodiments, and the advantages and features of the present invention will become clearer as a result. However, these embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. Those skilled in the art should understand that modifications or substitutions can be made to the details and form of the technical solutions of the present invention without departing from the spirit and scope of the present invention, but all such modifications and substitutions fall within the protection scope of the present invention.

[0055] In all embodiments and comparative examples of this invention, the styrene-isoprene-styrene block copolymers are linear structures.

[0056] Example 1 In this embodiment, a drug-loaded gel sample was prepared according to the formulation in Table 1, denoted as Gel One, as follows: Table 1 Drug-loaded gel formulation

[0057] Note: The molecular weight of the styrene-isoprene-styrene block copolymer is Mn=180000, and the isoprene content is 80%; the number average molecular weight of polyisobutylene is 600.

[0058] Example 2 In this embodiment, drug-loaded gel samples were prepared according to the formulation in Table 2, as detailed below: Table 2 Drug-loaded gel formulations

[0059] Note: The molecular weight of the styrene-isoprene-styrene block copolymer is Mn=80000, and the isoprene content is 65%; the number average molecular weight of polyisobutylene is 600.

[0060] Comparative Example 1 The difference between this comparative example and Example 1 lies in the different ratios of styrene-isoprene-styrene block copolymer and polyisobutylene. Drug-loaded gel samples were prepared according to the formulations in Table 3, as detailed below: Table 3 Drug-loaded gel formulations

[0061] Note: The molecular weight, isoprene content, and number-average molecular weight of the styrene-isoprene-styrene block copolymer are the same as in Example 1.

[0062] Comparative Example 2 The difference between this comparative example and Example 1 lies in the different ratios of styrene-isoprene-styrene block copolymer and polyisobutylene. Drug-loaded gel samples were prepared according to the formulations in Table 4, as detailed below: Table 4 Drug-loaded gel formulations

[0063] Note: The molecular weight, isoprene content, and number-average molecular weight of the styrene-isoprene-styrene block copolymer are the same as in Example 1.

[0064] Comparative Example 3 The difference between this comparative example and Example 1 is that it does not contain hydrogenated rosin glycerol ester. The drug-loaded gel sample was prepared according to the formulation in Table 5, as follows: Table 5 Drug-loaded gel formulations

[0065] Note: The molecular weight, isoprene content, and number-average molecular weight of the styrene-isoprene-styrene block copolymer are the same as in Example 1, and the ratio of styrene-isoprene-styrene block copolymer to polyisoprene is the same as in Example 1.

[0066] Comparative Example 4 The only difference between this comparative example and Example 1 is the content of isoprene in the styrene-isoprene-styrene block copolymer, which is 85%. All other conditions are the same.

[0067] Comparative Example 5 The only difference between this comparative example and Example 1 is the content of isoprene in the styrene-isoprene-styrene block copolymer, which is 60%. All other conditions are the same.

[0068] Preparation Example 1 Blank patch preparation: The gel samples from Examples 1, 2, 1, 2, 4, and 5 were prepared into blank patch samples without the addition of any drug components according to the following preparation methods, namely Sample 1-1, Sample 2-1, Sample 3-1, Sample 4, Sample 6-1, and Sample 7-1.

[0069] (1) Add each component of the drug-loaded gel used to prepare the patch in Example 1, Example 2, Comparative Example 1 and Comparative Example 2 to a melting tank equipped with a precision metering pump (glue pump), and obtain the glue solution after complete melting for later use; (2) Turn on the coating machine and accurately pump the adhesive into the coating machine using the adhesive pump, at a rate of 200g / m³. 2 The content standard is evenly coated onto the non-woven backing fabric, covered with release paper, and then die-cut into patches of a certain size.

[0070] Preparation Example 2 This preparation example prepared a patch drug component for treating subcutaneous ecchymosis. The specific components and preparation process are as follows: The prescription includes: 2 parts by weight of peony bark, 2 parts by weight of red peony root, and 1 part by weight of Glauber's salt.

[0071] Drug component preparation process: (1) Weigh each medicinal material according to the weight ratio, decoct the peony bark and red peony root with 3 times the weight of water 4 times, decoct for 1 hour each time, and concentrate to a liquid with a relative density of 1.25 (60℃) for later use; (2) Add Glauber's salt to (1) and set aside.

[0072] Test Example 1 Heat resistance test: Take two patches each of the following prepared patch samples (7cm × 10cm): Sample 1-1, Sample 2-1, Sample 3-1, Sample 4, Sample 6-1, and Sample 7-1. Remove the release paper, heat at 60℃ for 2 hours, and observe after natural cooling as follows: Sample 1-1: The non-woven fabric backing showed no oil seepage, no excess adhesive around the edges, and the ointment surface (the drug-carrying gel surface applied to the skin) had a glossy appearance. The ointment surface remained sticky when touched with a finger and could still be repeatedly peeled off more than 10 times. No adhesive residue remained on the hand when touched, and no residue was left when removed from the skin. The cohesion and application performance were excellent, meeting the quality requirements for patch in the Chinese Pharmacopoeia.

[0073] Sample 2-1: The non-woven fabric backing showed no oil seepage, no excess adhesive around the edges, and the ointment surface (the drug-carrying gel surface applied to the skin) had a glossy appearance. The ointment surface remained sticky when touched with a finger and could still be repeatedly peeled off more than 10 times. No adhesive residue remained on the hand when touched, and no residue was left when removed from the skin. The cohesion and application performance were excellent, meeting the quality requirements for patch in the Chinese Pharmacopoeia.

[0074] Sample 3-1: The non-woven fabric backing showed no obvious oil seepage on the back, no obvious glue overflow around the edges, and the paste surface (the drug-carrying gel surface applied to the skin) had a glossy feel. The paste surface was still sticky when touched with a finger. It could only be repeatedly peeled and removed 7 times. When the paste surface was touched with a hand, there was no glue residue left on the hand. When it was applied to the skin and removed, there was a very slight and inconspicuous residue.

[0075] Sample 4: The non-woven fabric backing showed obvious glue seepage. When touched, the backing surface was noticeably sticky, with a significant amount of glue overflowing around the edges. When the paste was touched, glue residue remained on the hand. When removed from the skin, a considerable amount of residue remained, making it impossible to reapply. This indicates that its cohesiveness and adhesion performance are very poor, failing to meet the performance requirements of the patch and not complying with the quality requirements for patches in the Chinese Pharmacopoeia.

[0076] Sample 6-1: The non-woven fabric backing showed oil seepage on the back, with no excess adhesive around the edges. The paste surface (the drug-carrying gel surface applied to the skin) had a glossy appearance. The paste surface was still sticky when touched with a finger. It could only be repeatedly peeled and removed 6 times. When the paste surface was touched with a hand, there was no adhesive residue left on the hand. When it was applied to the skin and removed, there was no residue.

[0077] Sample 7-1: There was no obvious oil seepage on the back of the non-woven fabric backing, but there was slight glue overflow around the edges. The paste surface (the drug-carrying gel surface applied to the skin) had a glossy feel. The paste surface was still sticky when touched with a finger. It could only be repeatedly peeled and removed 4 times. When the paste surface was touched with a hand, there was glue residue on the hand. When it was applied to the skin and removed, there was some residue.

[0078] Test Example 2 Formability test: Take two pieces each of the patch samples 1-1, 2-1, 3-1, 4, 6-1 and 7-1 prepared in Preparation Example 1 (7cm × 10cm in size), place them in a constant temperature and humidity chamber at 37℃ and 64% relative humidity for 30 minutes, remove them, fix the samples on a flat steel plate with the steel plate at an angle of 60 degrees to the horizontal plane, and place them for 24 hours. Observe as follows: Sample 1-1: The ointment showed no dripping, exhibiting excellent performance and meeting the quality requirements for patch in the Chinese Pharmacopoeia.

[0079] Sample 2-1: The ointment showed no dripping, exhibiting excellent performance and meeting the quality requirements for patch in the Chinese Pharmacopoeia.

[0080] Sample 3-1: There was exudation on the back of the patch, and the cohesiveness of the drug-loaded gel was poor, which could not meet the performance requirements of the patch and did not meet the quality requirements of the Chinese Pharmacopoeia for patches.

[0081] Sample 4: There was seepage on the back of the patch and the drug-loaded gel overflowed from the non-woven fabric at the lower edge of the patch, indicating that the patch surface had some flow and displacement, the cohesion of the drug-loaded gel was poor, and it could not meet the performance requirements of the patch, and did not meet the quality requirements of the Chinese Pharmacopoeia for patches.

[0082] Sample 6-1: The presence of drug-loaded gel overflowing from the nonwoven fabric at the lower edge of the patch indicates that the patch surface has some flow and displacement, and the cohesion of the drug-loaded gel is poor, failing to meet the performance requirements of the patch.

[0083] Sample 7-1: The presence of drug-loaded gel overflowing from the nonwoven fabric at the lower edge of the patch indicates that the patch surface has some flow and displacement, and the cohesion of the drug-loaded gel is poor, failing to meet the performance requirements of the patch.

[0084] The results of Test Examples 1 and 2 show that the ratio of styrene-isoprene-styrene block copolymer to polyisobutylene, as well as the isoprene content in the styrene-isoprene-styrene block copolymer, significantly affects the heat resistance and cohesiveness of the drug-loaded gel. The ratio of styrene-isoprene-styrene block copolymer to polyisobutylene, and the isoprene content in the styrene-isoprene-styrene block copolymer, are not within the scope of this invention. In these cases, the heat resistance and cohesiveness of the drug-loaded gel are significantly reduced, and the reduced cohesiveness leads to a decrease in drug loading capacity.

[0085] Test Example 3 This experiment investigated the safety of the blank patch in this invention. The test sample used in the experiment was sample 1-1, and a skin irritation test was conducted on guinea pigs, as detailed below: Experimental animals: guinea pigs, 250-300g, half male and half female.

[0086] Animal husbandry requirements: The temperature in the animal room should be controlled at 22±2℃, the humidity at around 55%, and the ammonia concentration below 20ppm. A 12h:12h light-dark lighting system should be used, and ventilation should be carried out regularly. All animals should be fed a complete nutritional diet, each animal should be individually labeled, and they should be kept in stainless steel cages with free access to food and water.

[0087] Single-dose skin irritation of intact and damaged guinea pig skin: Healthy guinea pigs were divided into two groups of four each: one with normal skin and one with damaged skin. A self-comparison method was used, with half males and half females. 24 hours before the experiment, the treatment area was shaved, one patch on each side, with a 3cm × 3cm area removed. In the damaged skin group, a crisscross pattern was drawn at the treatment site until bleeding occurred. A blank patch (Sample 1-1) prepared according to this invention was applied to the left side of the shaved area as the test area, and the right side as the control area, fixed with gauze. The blank patch was removed after 24 hours. The skin at the treatment site was carefully observed for erythema and edema at 1 hour, 24 hours, and 72 hours, and skin irritation was evaluated according to the requirements of the new drug toxicology technical specifications.

[0088] Skin irritation assessment: (1) Scoring criteria: Erythema: No erythema 0 points; Mild erythema (barely visible) 1 point; Moderate erythema (clearly visible) 2 points; Severe erythema 3 points; Purplish-red erythema to mild eschar formation 4 points. Edema: No edema 0 points; Mild edema (barely visible) 1 point; Moderate edema (clearly raised) 2 points; Severe edema (skin raised 1mm, clear outline) 3 points; Severe edema (skin raised >1mm and enlarging) 4 points. Maximum total score 8 points.

[0089] (2) Evaluation criteria for skin irritation intensity: 0-0.49 points: no irritation; 0.50-2.99 points: mild irritation; 3.00-5.99 points: moderate irritation; 6.00-8.00 points: strong irritation.

[0090] After the administration of the drug, the control area and the test area of ​​sample 1-1 were compared and observed. There were no irritation reactions such as erythema, dry skin, or desquamation at the test sites, and the intensity of skin irritation reaction was <0.5 points. The above experimental results demonstrate that the patch in this invention can effectively prevent skin irritation.

[0091] Test Example 4 Preparation of medicated patches: The drug components prepared in Preparation Example 2 were added to the drug-loaded gels used in the preparation of patches in Examples 1, 2, 3, 4, and 5, respectively, and samples were prepared according to the following preparation methods. They were respectively recorded as Sample 1-2, Sample 2-2, Sample 5, Sample 6-2, and Sample 7-2, and the sample preparation effects were recorded.

[0092] Preparation of a patch for treating subcutaneous ecchymosis: (1) Add the prepared drug components from Preparation Example 2 into a storage tank equipped with a precision metering pump (pharmaceutical pump) for later use; (2) Add the drug-loaded gel for preparing the patch to a melting tank equipped with a precision metering pump (glue pump), and obtain the adhesive solution after the gel is completely melted; (3) Turn on the coating machine and pump the drug components and adhesive solution into the coating machine through the drug pump and adhesive pump respectively in a mass ratio of 20:80. Mix the adhesive solution and drug solution quickly and evenly at 90°C for 50 seconds to obtain the drug-adhesive mixture. (4) Mix the prepared adhesive mixture at 200g / m 2 The content standard is evenly coated onto the non-woven backing fabric, covered with release paper, and then die-cut into patches of a certain size.

[0093] The following conclusions were drawn from the preparation experiment with added chemicals: Sample 1-2 processing and preparation: The adhesive-medicine mixture showed excellent homogenization, the patch was generally flat, the backing fabric was naturally stretched, and the surface of the coated patch had a uniform color with no obvious color difference; indicating that the sample had excellent processing performance. Sample 2-2 processing and preparation: The adhesive-medicine mixture showed excellent homogenization, the patch was generally flat, the backing fabric was naturally stretched, and the surface of the coated patch had a uniform color with no obvious color difference; indicating that the sample had excellent processing performance. Sample 5 processing and preparation: Compared with the homogenization process of samples 1-2, under the same mixing conditions and mixing time, there is a clear mixing boundary between the drug component and the adhesive. When the mixture is observed to be uniform by the naked eye, the homogenization time increases to 4 times. The adhesive layer of the coated patch shows obvious discontinuous texture, the patch is curled, and there is a striped color difference on the patch surface, indicating that the sample has poor processing performance and affects the patch preparation. Sample 6-2 processing and preparation: The mixing effect of the adhesive and medicine was good when observed with the naked eye, but the adhesive layer of the applied patch had some discontinuous texture and some stripe color difference.

[0094] Sample 7-2 processing and preparation: The mixing effect of the adhesive and medicine was good when observed with the naked eye, but the adhesive layer of the applied patch had some discontinuous texture and some stripe color difference.

[0095] Test Example 5 Heat resistance test: Take two patches (7cm×10cm each) of the patch samples 1-2 and 2-2 prepared in test example 4, remove the release paper, heat at 60℃ for 2 hours, and let cool naturally. There is no oil seepage on the back of the non-woven fabric backing, the patch surface has a glossy feel, it is still sticky when touched with a finger, and it can still be repeatedly peeled and removed more than 10 times. All of these meet the quality requirements of the Chinese Pharmacopoeia for patches.

[0096] Test Example 6 Excipient test: Take two patches (7cm×10cm each) of the patch samples 1-2 and 2-2 prepared in test example 4, place them in a constant temperature and humidity chamber at 37℃ and 64% relative humidity for 30 minutes, take them out, fix the samples on a flat steel plate with the steel plate at an angle of 60 degrees to the horizontal plane, and place them for 24 hours. There is no dripping on the surface of the patch, which meets the quality requirements of the Chinese Pharmacopoeia for patch.

[0097] Test Example 7 Drug Dosage Comparison Experiment: Samples 1-2, 2-2, 6-2, and 7-2 of the patch prepared in Test Example 4 were compared. It was found that at the same drug dosage, the product quality of samples 6-2 and 7-2 was poor and did not meet the quality control standards. Comparison of samples 1-2, 6-2, and 7-2 indicates that the isoprene content of the styrene-isoprene-styrene block copolymer affects the cohesive strength; that is, the isoprene content of the styrene-isoprene-styrene block copolymer indirectly affects the drug loading. Specific results are as follows: Samples 1-2: Excellent application effect, no residue on the skin surface, and the skin surface is clean and not sticky. The surface of the applied sample is smooth, intact and undamaged. Sample 2-2: Excellent application effect, no residue on the skin surface, and the skin surface is clean and not sticky. The surface of the applied sample is smooth, intact and undamaged. Sample 6-2: After application, there was a lot of residue on the skin surface, and the surface of the applied sample was rough and obviously damaged. Sample 7-2: After application, there was a lot of residue on the skin surface, and the surface of the applied sample was rough and obviously damaged.

[0098] Clinical Trial Example 1: Results of the Clinical Trial of the Patch for Treating Subcutaneous Ecchymosis in this Invention (1) Research subjects The case studies included 65 hospitalized patients who developed local ecchymosis after DSA (cerebral angiography). All selected patients met the ecchymosis evaluation criteria: ecchymosis was defined as having a long diameter D of 0.5 cm or more, with 0.5 cm ≤ D < 2.0 cm being mild, 2.0 ≤ D < 5.0 cm being moderate, and D ≥ 5.0 cm being severe. If induration had formed, it was classified as severe.

[0099] The 65 patients were divided into a control group and an observation group: Control group 1: 21 cases, 12 males and 9 females, aged 49-71 (58.43±6.07) years; among them, 3 cases were mild, 11 cases were moderate and 7 cases were severe. Control group 2: 22 cases, 11 males and 11 females, aged 51-73 (59.18±5.79) years; among them, 5 cases were mild, 8 cases were moderate and 9 cases were severe. Observation group: 22 cases, 14 males and 8 females, aged 48-69 (57.91±5.41) years; among them, 3 cases were mild, 12 cases were moderate and 7 cases were severe.

[0100] The results of the three groups of blood routine tests were all within the normal range. There were no statistically significant differences in general information such as age, location of ecchymosis and operation technique (p>0.05), and they were comparable.

[0101] (2) Treatment methods Observation group: Apply the patch samples 1-2 prepared in test example 4 to the local area of ​​ecchymosis (avoiding the puncture point, which is covered and protected with a sterile dressing), with the area exceeding 1 cm of the ecchymosis area. 2 -2cm 2 Observe for any skin redness, swelling, itching, or allergic reactions during the application process. Apply the patches twice daily for 4 hours each time, for a total of 3 days.

[0102] Control Group 1: Wet dressing was prepared using the drug components prepared in Preparation Example 2. The specific method was as follows: a disposable compressed towel was used to soak and cover the ecchymosis area (avoiding the puncture point, which was covered and protected with a sterile dressing), extending the area beyond 1 cm of the ecchymosis area. 2 -2cm 2 Wrap the outer layer with plastic wrap to prevent the medicine from staining clothes and to prevent moisture evaporation from reducing efficacy. Apply twice daily for 4 hours each time, for a total of 3 days of treatment.

[0103] Control group 2: 50% magnesium sulfate solution was applied to the ecchymosis area using a disposable compressed towel (avoiding the puncture site, which was covered with a sterile dressing for protection), extending over 1 cm of the ecchymosis area. 2 -2cm 2 Wrap the outer layer with plastic wrap to prevent the medicine from staining clothes and to prevent moisture evaporation from reducing efficacy. Apply twice daily for 4 hours each time, for a total of 3 days of treatment.

[0104] Each of the three groups has a designated person responsible for daily observation, medication changes, assessment, and detailed record-keeping.

[0105] (3) Efficacy evaluation criteria All three groups underwent a 3-day treatment course, with data collection commencing after 3 days. Efficacy evaluation was conducted according to the "Standards for Diagnosis and Efficacy Assessment of Traditional Chinese Medicine Diseases." The area of ​​ecchymosis was roughly estimated by multiplying the longest axis of the ecchymosis by its short axis.

[0106] The treatment is considered ineffective if there is no change in the local ecchymosis or induration and no relief of pain; the local ecchymosis area shrinks by ≥3cm. 2 Significant improvement is indicated by changes in color, reduction in the size of the induration, and lessening of pain; complete disappearance of ecchymosis or a reduction in size of ≥6cm. 2 A full recovery is indicated by the disappearance of the nodules and the relief of pain.

[0107] (4) Clinical observation results 1) Comparison of therapeutic effects among the three groups The efficacy evaluation of all three groups showed that the intervention was more effective than the intervention, with the observation group showing a more significant effect (p=0.013), as shown in Table 6.

[0108] Table 6 Comparison of therapeutic effects among the three groups

[0109] 2) Comparison of three VAS groups All three groups showed a decrease in VAS (Visual Analogue Scale) scores after intervention compared to before intervention, with the observation group showing a more significant decrease (p=0.003), as shown in Table 7. Among these, "M(P0, P... 100 In the figure, M represents the median, P0 represents the minimum VAS score, and P 100 This represents the maximum value in the VAS score.

[0110] Table 7 Comparison of three groups of VAS

[0111] 3) Comparison of the dissipation time of the three groups of indurations In the observation group, 7 patients developed subcutaneous induration, and the average time for the induration to dissipate after intervention was 5-20 (14±4.93) hours; in control group 1, 7 patients developed subcutaneous induration, and the average time for the induration to dissipate after intervention was 11-25 (19±5.17) hours; in control group 2, 5 patients developed subcutaneous induration, and the average time for the induration to dissipate after intervention was 15-29 (21±5.48) hours (see Table 8).

[0112] Table 8 Comparison of induration dissipation time in three groups

[0113] Studies have shown that the therapeutic effect of the observation group was better than that of control groups 1 and 2 (p values ​​< 0.05), indicating that the traditional Chinese medicine patch for treating subcutaneous ecchymosis of the present invention is more effective in removing blood stasis. After intervention, the VAS pain scores of patients in all three groups decreased, and the decrease was more significant in the observation group (p values ​​< 0.05), suggesting that the traditional Chinese medicine patch for treating subcutaneous ecchymosis of the present invention has a good effect on improving limb pain.

[0114] The above detailed description is a specific description of one of the feasible embodiments of the present invention. This embodiment is not intended to limit the patent scope of the present invention. All equivalent implementations or modifications that do not depart from the present invention should be included within the scope of the technical solution of the present invention.

Claims

1. A traditional Chinese medicine plaster for treating subcutaneous ecchymosis, characterized in that, The product includes a pharmaceutical ingredient and a drug-loaded gel. The pharmaceutical ingredient is made from raw materials including peony bark, red peony root, and mirabilite. The drug-loaded gel, by weight percentage, includes the following components: 30-40% styrene-isoprene-styrene block copolymer, 19-24% tackifier, 35-40% softener, 4-7% inorganic salts, and 0.1-2% sodium polyacrylate. The isoprene content in the styrene-isoprene-styrene block copolymer is 65-80% by mass.

2. The traditional Chinese medicine plaster according to claim 1, characterized in that, The amount of the drug component used is 2%-50% of the total mass of the drug component and the drug-loaded gel.

3. The traditional Chinese medicine plaster according to claim 1, characterized in that, The drug-loaded gel comprises, by weight percentage, the following components: 36% styrene-isoprene-styrene block copolymer, 20% tackifier, 38% softener, 4.9% inorganic salts, and 1% sodium polyacrylate.

4. The traditional Chinese medicine plaster according to claim 1, characterized in that, The raw materials of the medicinal ingredients, by weight, include: 1-10 parts by weight of peony bark, 1-10 parts by weight of red peony root, and 1-10 parts by weight of Glauber's salt.

5. The traditional Chinese medicine plaster according to claim 4, characterized in that, The raw materials of the medicinal ingredients, by weight, include: 2-6 parts by weight of peony bark, 1-4 parts by weight of red peony root, and 1-4 parts by weight of Glauber's salt.

6. The traditional Chinese medicine plaster according to claim 5, characterized in that, The raw materials of the drug components, by weight, include: 2 parts by weight of peony bark, 2 parts by weight of red peony root, and 1 part by weight of Glauber's salt.

7. The traditional Chinese medicine plaster according to claim 1, characterized in that, The inorganic salts include at least one of calcium carbonate, titanium dioxide, zinc oxide, and talc; the tackifiers include one or more of rosin resin, rosin glycerol ester, hydrogenated rosin, hydrogenated rosin glycerol ester, C5 petroleum resin and its derivatives, C9 petroleum resin, epoxy resin, terpene resin, polyisobutylene, polyurethane, polyamide, polyacrylic acid, and silicone; the tackifier has a mass percentage of 5%-50% in the drug-loaded gel.

8. The traditional Chinese medicine plaster according to claim 1, characterized in that, The softener includes one or more of naphthenic oil, polyisobutylene, liquid paraffin, olive oil, soybean oil and their derivatives; the softener has a mass percentage of 12%-50% in the drug-loaded gel.

9. The traditional Chinese medicine plaster according to claim 1, characterized in that, The mass ratio of the styrene-isoprene-styrene block copolymer to the plasticizer is 0.9-1.0:1; the number average molecular weight of the styrene-isoprene-styrene block copolymer is 80,000-180,000.

10. The traditional Chinese medicine plaster according to any one of claims 1-9, characterized in that, The herbal plaster also includes a backing fabric and a protective layer. The backing fabric is one of non-woven fabric, woven fabric, biaxial elastic fabric, uniaxial elastic fabric, and polyurethane film. The thickness of the backing fabric is between 5μm and 1500μm. The protective layer includes at least one of release paper and release film. The thickness of the protective layer is between 0.01mm and 0.5mm.

11. The traditional Chinese medicine plaster according to claim 10, characterized in that, The total content of the drug components and drug-loaded gel in the traditional Chinese medicine patch is 50 g / m³. 2 -300g / m 2 .

12. The traditional Chinese medicine plaster according to any one of claims 1-9, characterized in that, The drug-loaded gel further includes an antioxidant; the antioxidant includes at least one of BHT264 and antioxidant 1010, and the antioxidant has a mass percentage of 0.01-1%.

13. A method for preparing a traditional Chinese medicine plaster according to any one of claims 10 or 11, characterized in that, The steps include: (1) Boil peony bark and red peony root in water, concentrate the decoction and add Glauber's salt to obtain the medicinal components; (2) After the drug-loaded gel is melted, it is mixed evenly with the drug components to obtain a gel-drug mixture; (3) Apply the adhesive mixture to the backing cloth and cover it with a protective layer to obtain the final product.

14. The preparation method according to claim 13, characterized in that, In step (1), peony bark and red peony root are decocted in water 1-8 times.

15. The preparation method according to claim 14, characterized in that, In step (1), peony bark and red peony root are decocted with 2-7 times their weight of water 2-6 times, each time for 30-120 minutes.

16. The preparation method according to claim 15, characterized in that, In step (1), the peony bark and red peony root are decocted four times with three times their weight of water, each time for 60 minutes.

17. The use of the traditional Chinese medicine patch according to any one of claims 1-12 or the traditional Chinese medicine patch prepared by any one of claims 13-16 in the preparation of a drug for treating subcutaneous ecchymosis.

18. The use according to claim 17, characterized in that, The aforementioned subcutaneous ecchymosis refers to the state in which blood remains in the subcutaneous tissue.

19. The use according to claim 18, characterized in that, The aforementioned subcutaneous ecchymosis refers to a condition in which blood remains in the subcutaneous tissue due to damage to capillaries, veins, or arteries caused by various traumas or vascular punctures; or due to blood clotting system disorders.

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