External detumescence pharmaceutical composition and preparation method thereof

Abstract

The invention belongs to the technical field of medicine, and provides an external detumescence pharmaceutical composition and a preparation method thereof, the external detumescence pharmaceutical composition comprises, by weight, 18-22 parts of mirabilite, 0.05-0.15 part of borneol, 5-15 parts of schizonepeta volatile oil and 3-7 parts of angelica volatile oil. The herba schizonepetae volatile oil and the radix angelicae sinensis volatile oil which have the property of combining medicines with auxiliary medicines are creatively used for preparing the transdermal patch, so that the efficacy of the herba schizonepetae volatile oil and the efficacy of the radix angelicae sinensis can be exerted, and the herba schizonepetae volatile oil and the radix angelicae sinensis volatile oil cooperate with the mirabilite and the borneol to exert the curative effect, enhance the anti-inflammatory, swelling-relieving and pain-relieving effects, play a role in promoting permeation and enhance the transdermal permeation of effective components; the bioavailability is improved. The external detumescence pharmaceutical composition disclosed by the invention has a synergistic effect and remarkable anti-inflammatory and detumescence effects.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines and relates to an external detumescent medicine composition and a preparation method thereof. Background Art

[0002] Swelling was first recorded in Huangdi Neijing Lingshu Zhanglun: "The cold qi is below, the Yingwei is stagnant, the cold qi goes up, the true qi and the evil qi attack each other, and the two qi fight against each other, which causes swelling." Swelling is caused by abnormal water metabolism, and swelling is related to poor qi movement.

[0003] Modern medicine believes that swelling refers to the clinical manifestation of the increase in volume of muscle, skin, mucous membrane and other tissues due to inflammation or congestion during the course of the disease.

[0004] Bone injury and soft tissue swelling generally have clear causes, such as fractures and trauma. The reason is that swelling is a stress response of tissue cells. The most direct manifestation of bone injury and soft tissue swelling is local swelling and pain, which requires timely treatment of swelling and analgesia. If reasonable treatment is not adopted, it may lead to local tissue necrosis, delayed fracture healing, local joints, etc., causing more serious consequences.

[0005] Knee osteoarthritis, also known as degenerative knee arthritis or senile knee arthritis, is usually caused by factors such as joint injury, degeneration, and excessive weight. Common symptoms include knee pain, swelling, and movement disorders. Knee swelling can cause stiffness in the muscles and ligaments around the joint, further aggravating movement disorders, severely reducing the quality of life, and causing great distress to the patient's body and mind.

[0006] Hydrogel patch is a new type of transdermal drug delivery carrier made of water-soluble polymer materials, moisturizers, water and fillers. It has the unique advantages of large drug loading capacity, high transdermal drug absorption efficiency, no allergy and no irritation, moderate viscosity without tearing the skin, soft paste without foreign body sensation, long drug action time and easy use. It does not affect the normal physiological activities and life of patients, and is also particularly suitable as a carrier for transdermal drug delivery of traditional Chinese medicine. Actively developing traditional Chinese medicine hydrogel external application patches for detumescence has important clinical application value and social significance. Summary of the invention

[0007] In order to make up for the deficiencies of the prior art, the present invention provides a new external detumescent pharmaceutical composition with reasonable formula, good efficacy and safe medication, and the pharmaceutical composition has significant anti-inflammatory and detumescent effects.

[0008] The invention also provides a method for preparing the external detumescence medicine composition.

[0009] The present invention also provides medical use of the external detumescence medicine composition.

[0010] The present invention also provides a patch containing the external detumescent medicine composition.

[0011] The present invention also provides a method for preparing a patch containing the external detumescent medicine composition.

[0012] Specifically, the technical problem to be solved by the present invention is achieved through the following technical solutions.

[0013] The invention provides an external detumescent medicinal composition, which consists of mirabilite and borneol.

[0014] Specifically, the external detumescent pharmaceutical composition is composed of 18-22 parts of mirabilite, 0.05-0.15 parts of borneol, 5-15 parts of schizonepeta volatile oil and 3-7 parts of angelica volatile oil by weight.

[0015] In one embodiment of the present invention, the external detumescent pharmaceutical composition is composed of 20 parts of mirabilite, 0.1 parts of borneol, 10 parts of schizonepeta volatile oil and 5 parts of angelica volatile oil by weight.

[0016] Furthermore, the preparation method of the schizonepeta volatile oil is as follows: the schizonepeta decoction pieces are extracted by steam distillation or supercritical CO2 extraction to obtain the volatile oil.

[0017] Furthermore, the preparation method of the Nepeta volatile oil is as follows: Nepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed Nepeta is extracted in water for 30 minutes to obtain Nepeta volatile oil.

[0018] Furthermore, the preparation method of the angelica volatile oil is as follows: the angelica slices are extracted by steam distillation or supercritical CO2 extraction to obtain the volatile oil.

[0019] Furthermore, the preparation method of the angelica volatile oil is as follows: the angelica is crushed into 100 mesh fine powder, extracted by supercritical extraction under the conditions of pressure 35MPa and temperature 45°C, the extraction time is 2h, the number of extractions is 1, and the carbon dioxide flow rate is 30mL / min to obtain angelica volatile oil.

[0020] The preparation method of the external detumescent medicine composition of the present invention is as follows: grind and mix Glauber's salt and borneol according to weight, and then add schizonepeta volatile oil and angelica volatile oil to obtain the medicine composition.

[0021] The external detumescence pharmaceutical composition of the present invention can be prepared into an external preparation according to conventional methods.

[0022] Furthermore, the dosage form of the external preparation is a lotion, a patch, a paste, an ointment, a gel, a film coating or a papule.

[0023] Furthermore, the dosage form of the external preparation is a patch.

[0024] The invention provides use of an external detumescence medicine composition in preparing a detumescence treatment medicine.

[0025] The invention provides use of an external detumescent medicine composition in preparing a medicine for treating swelling caused by knee osteoarthritis.

[0026] The present invention also provides a patch of an external detumescent drug composition, which is composed of a backing layer, a drug-containing adhesive layer and a protective layer. The drug-containing adhesive layer is composed of the following components in percentage by weight: 35%-45% of the external detumescent composition, 35%-45% of a hydrophilic gel skeleton, 10%-20% of a moisturizer, 0.5%-3% of a transdermal penetration enhancer and 0%-0.1% of a preservative.

[0027] Furthermore, the external detumescent composition is composed of 18-22 parts of Glauber's salt, 0.05-0.15 parts of borneol, 5-15 parts of Schizonepeta volatile oil and 3-7 parts of Angelica dahurica volatile oil by weight.

[0028] Furthermore, the hydrophilic gel skeleton is one or more of hydroxypropyl methylcellulose, hydroxyethyl cellulose or hydroxypropyl cellulose.

[0029] Furthermore, the moisturizing agent is glycerin or polyethylene glycol 400.

[0030] Furthermore, the transdermal penetration enhancer is azone or propylene glycol.

[0031] Furthermore, the preservative is ethylparaben or methylparaben.

[0032] The preparation method of the external detumescent pharmaceutical composition of the present invention is as follows:

[0033] (1) Grinding sodium sulfate and borneol by weight, mixing, and then adding volatile oil of schizonepeta tenuifolia and volatile oil of angelica sinensis to obtain a topical pharmaceutical composition; (2) Adding water to a hydrophilic gel skeleton, leaving it for 24 hours to fully swell, mixing it in a water bath and adding a moisturizer, stirring and mixing it thoroughly to obtain a transparent and viscous hydrogel matrix; (3) Dispersing the topical pharmaceutical composition obtained in step (1) in the hydrogel matrix prepared in step (2), adding a transdermal penetration enhancer and a preservative, mixing them evenly, removing bubbles by ultrasonication, applying it on a backing layer while it is hot, and covering it with a protective layer after drying to obtain a topical pharmaceutical composition.

[0034] In the pharmaceutical composition of the present invention, mirabilite is salty, bitter, cold in nature, and belongs to the stomach meridian and the large intestine meridian. It has the functions of purging and relieving constipation, moistening dryness and softening hard masses, clearing away heat and reducing swelling. It is mainly used to treat damp-heat stagnation, abdominal distension and pain, dry stool, intestinal carbuncle swelling and pain, and externally treats mastitis, hemorrhoid swelling and pain, etc.; borneol is pungent, bitter, slightly cold in nature, and belongs to the liver meridian and the lung meridian. It can open the mind and refresh the mind, clear away heat and relieve pain. It is mainly used to treat febrile coma, convulsion, stroke and phlegm syncope, qi stagnation and sudden syncope, coma caused by evil, chest obstruction and heart pain, red eyes, mouth sores, sore throat, pus in the ear canal, etc. The external-use pharmaceutical composition composed of mirabilite, borneol, schizonepeta volatile oil and angelica volatile oil of the present invention has synergistic effect and plays the role of anti-inflammatory and reducing swelling.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] (1) The present invention creatively uses Nepeta tenuifolia volatile oil and Angelica sinensis volatile oil, which have the property of "drug-adjuvant combination", for the preparation of transdermal patches, which can not only exert the pharmacological effects of Nepeta tenuifolia and Angelica sinensis themselves, but also synergize with Glauber's salt and borneol to exert therapeutic effects, enhance the anti-inflammatory, anti-edema and analgesic effects, and play a role in promoting penetration, thereby enhancing the transdermal penetration of the active ingredients and increasing their bioavailability.

[0037] (2) External treatment with Chinese medicine is an important part of traditional Chinese medicine. Through external administration, the medicine can directly reach the diseased area, thereby achieving the purpose of eliminating pathogens and curing diseases. The external detumescence drug composition of the present invention produces a synergistic effect, and has a significant anti-inflammatory and detumescence effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Comparison of foot swelling in each group

[0039] Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01; compared with Example 1 group, & P<0.05, && P<0.05.

[0040] Figure 2 Comparison of serum TNF-α in each group

[0041] Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01; compared with Example 1 group, & P<0.05, && P<0.05.

[0042] Figure 3Comparison of serum IL-1β in each group

[0043] Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01; compared with Example 1 group, & P<0.05, && P<0.05.

[0044] Figure 4 Comparison of serum IL-6 in each group

[0045] Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01; compared with Example 1 group, & P<0.05, && P<0.05.

[0046] Figure 5 Comparison of serum IL-10 in each group

[0047] Compared with the sham operation group, # P<0.05, ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01; compared with Example 1 group, & P<0.05, && P<0.05.

[0048] Figure 6 To compare the clinical efficacy of each group. Specific embodiments

[0049] The content of the present invention is further described in detail below through specific implementation methods, but this should not be understood as the scope of the above subject matter of the present invention is limited to the following examples. The following examples are used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. If a person of ordinary skill in the art modifies or replaces the technical solution of the present invention with an equivalent without departing from the essence and scope of the technical solution of the present invention, it still belongs to the scope of protection of the present invention.

[0050] Example 1

[0051] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 42.9% of an external detumescent composition, 40.0% of a hydrophilic gel skeleton, 15.0% of a moisturizer, 2.0% of a transdermal penetration enhancer and 0.1% of a preservative.

[0052] The external detumescent composition consists of 20 parts of mirabilite, 0.1 parts of borneol, 10 parts of schizonepeta volatile oil and 5 parts of angelica volatile oil by weight.

[0053] The hydrophilic gel skeleton is hydroxypropyl methylcellulose, the moisturizer is glycerin, the transdermal penetration enhancer is azone, and the preservative is ethyl hydroxybenzoate.

[0054] The preparation method of Nepeta volatile oil is as follows: Nepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed Nepeta is extracted in water for 30 minutes to obtain Nepeta volatile oil.

[0055] The preparation method of angelica volatile oil is as follows: angelica is crushed into 100 mesh fine powder, extracted by supercritical extraction under the conditions of pressure 35 MPa and temperature 45°C, the extraction time is 2 hours, the number of extractions is 1 time, and the carbon dioxide flow rate is 30 mL / min to obtain angelica volatile oil.

[0056] The preparation method of the external detumescent pharmaceutical composition of the present invention is as follows:

[0057] (1) Grinding sodium sulfate and borneol by weight, mixing, and then adding volatile oil of schizonepeta tenuifolia and volatile oil of angelica sinensis to obtain a topical pharmaceutical composition; (2) Adding water to a hydrophilic gel skeleton, leaving it for 24 hours to fully swell, mixing it in a water bath and adding a moisturizer, stirring and mixing it thoroughly to obtain a transparent and viscous hydrogel matrix; (3) Dispersing the topical pharmaceutical composition obtained in step (1) in the hydrogel matrix prepared in step (2), adding a transdermal penetration enhancer and a preservative, mixing them evenly, removing bubbles by ultrasonication, applying it on a backing layer while it is hot, and covering it with a protective layer after drying to obtain a topical pharmaceutical composition.

[0058] Example 2

[0059] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 35.0% of an external detumescent composition, 41.9% of a hydrophilic gel skeleton, 20.0% of a moisturizer, 3.0% of a transdermal penetration enhancer and 0.1% of a preservative.

[0060] The external detumescent composition consists of 18 parts of mirabilite, 0.15 parts of borneol, 8 parts of schizonepeta volatile oil and 5 parts of angelica volatile oil by weight.

[0061] The hydrophilic gel skeleton is hydroxyethyl cellulose, the moisturizing agent is glycerin, the transdermal penetration enhancer is azone, and the preservative is methylparaben.

[0062] The preparation method of Nepeta volatile oil is as follows: Nepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed Nepeta is extracted in water for 30 minutes to obtain Nepeta volatile oil.

[0063] The preparation method of angelica volatile oil is as follows: angelica is crushed into 100 mesh fine powder, extracted by supercritical extraction under the conditions of pressure 35 MPa and temperature 45°C, the extraction time is 2 hours, the number of extractions is 1 time, and the carbon dioxide flow rate is 30 mL / min to obtain angelica volatile oil.

[0064] The preparation method is the same as Example 1.

[0065] Example 3

[0066] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer. The drug-containing adhesive layer is composed of the following components in percentage by weight: 35.0% of an external detumescent composition, 45.0% of a hydrophilic gel skeleton, 20.0% of a moisturizer and 3.0% of a transdermal penetration enhancer.

[0067] The external detumescent composition consists of 22 parts of mirabilite, 0.05 parts of borneol, 10 parts of schizonepeta volatile oil and 5 parts of angelica volatile oil by weight.

[0068] The hydrophilic gel skeleton is hydroxypropyl cellulose, the moisturizing agent is polyethylene glycol 400, and the transdermal penetration enhancer is azone.

[0069] The preparation method of Nepeta volatile oil is as follows: Nepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed Nepeta is extracted in water for 30 minutes to obtain Nepeta volatile oil.

[0070] The preparation method of angelica volatile oil is as follows: angelica is crushed into 100 mesh fine powder, extracted by supercritical extraction under the conditions of pressure 35 MPa and temperature 45°C, the extraction time is 2 hours, the number of extractions is 1 time, and the carbon dioxide flow rate is 30 mL / min to obtain angelica volatile oil.

[0071] The preparation method is the same as Example 1.

[0072] Example 4

[0073] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 45.0% of an external detumescent composition, 35.0% of a hydrophilic gel skeleton, 17.9% of a moisturizer, 2.0% of a transdermal penetration enhancer and 0.1% of a preservative.

[0074] The external detumescent composition is composed of 20 parts of mirabilite, 0.05 parts of borneol, 15 parts of schizonepeta volatile oil and 3 parts of angelica volatile oil by weight.

[0075] The hydrophilic gel skeleton is hydroxyethyl cellulose, the moisturizer is polyethylene glycol 400, the transdermal penetration enhancer is propylene glycol, and the preservative is ethyl hydroxybenzoate.

[0076] The preparation method of Nepeta volatile oil is as follows: Nepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed Nepeta is extracted in water for 30 minutes to obtain Nepeta volatile oil.

[0077] The preparation method of angelica volatile oil is as follows: angelica is crushed into 100 mesh fine powder, extracted by supercritical extraction under the conditions of pressure 35 MPa and temperature 45°C, the extraction time is 2 hours, the number of extractions is 1 time, and the carbon dioxide flow rate is 30 mL / min to obtain angelica volatile oil.

[0078] The preparation method is the same as Example 1.

[0079] Example 5

[0080] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 45.0% of an external detumescent composition, 44.0% of a hydrophilic gel skeleton, 10.0% of a moisturizer, 0.5% of a transdermal penetration enhancer and 0.1% of a preservative.

[0081] The external detumescent composition is composed of 22 parts of mirabilite, 0.1 parts of borneol, 5 parts of schizonepeta volatile oil and 7 parts of angelica volatile oil by weight.

[0082] The hydrophilic gel skeleton is hydroxypropyl cellulose, the moisturizing agent is glycerin, the transdermal penetration enhancer is propylene glycol, and the preservative is methylparaben.

[0083] The preparation method of Nepeta volatile oil is as follows: Nepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed Nepeta is extracted in water for 30 minutes to obtain Nepeta volatile oil.

[0084] The preparation method of angelica volatile oil is as follows: angelica is crushed into 100 mesh fine powder, extracted by supercritical extraction under the conditions of pressure 35 MPa and temperature 45°C, the extraction time is 2 hours, the number of extractions is 1 time, and the carbon dioxide flow rate is 30 mL / min to obtain angelica volatile oil.

[0085] The preparation method is the same as Example 1.

[0086] Example 6

[0087] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 40.5% of an external detumescent composition, 40.4% of a hydrophilic gel skeleton, 18.0% of a moisturizer, 1.0% of a transdermal penetration enhancer and 0.1% of a preservative.

[0088] The external detumescent composition is composed of 22 parts of mirabilite, 0.05 parts of borneol, 15 parts of schizonepeta volatile oil and 7 parts of angelica volatile oil by weight.

[0089] The hydrophilic gel skeleton is hydroxypropyl methylcellulose, the moisturizer is glycerin, the transdermal penetration enhancer is azone, and the preservative is ethyl hydroxybenzoate.

[0090] The preparation method of Nepeta volatile oil is as follows: Nepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed Nepeta is extracted in water for 30 minutes to obtain Nepeta volatile oil.

[0091] The preparation method of angelica volatile oil is as follows: angelica is crushed into 100 mesh fine powder, extracted by supercritical extraction under the conditions of pressure 35 MPa and temperature 45°C, the extraction time is 2 hours, the number of extractions is 1 time, and the carbon dioxide flow rate is 30 mL / min to obtain angelica volatile oil.

[0092] The preparation method is the same as Example 1.

[0093] Comparative Example 1

[0094] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 42.9% of an external detumescent composition, 40.0% of a hydrophilic gel skeleton, 15.0% of a moisturizer, 2.0% of a transdermal penetration enhancer and 0.1% of a preservative.

[0095] The external detumescence composition is composed of 20 parts of mirabilite, 0.1 parts of borneol and 15 parts of angelica volatile oil by weight.

[0096] The hydrophilic gel skeleton is hydroxypropyl methylcellulose, the moisturizer is glycerin, the transdermal penetration enhancer is azone, and the preservative is ethyl hydroxybenzoate.

[0097] The preparation method is similar to that of Example 1.

[0098] Comparative Example 2

[0099] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 42.9% of an external detumescent composition, 40.0% of a hydrophilic gel skeleton, 15.0% of a moisturizer, 2.0% of a transdermal penetration enhancer and 0.1% of a preservative.

[0100] The external detumescence composition is composed of 20 parts of mirabilite, 0.1 parts of borneol and 15 parts of schizonepeta volatile oil by weight.

[0101] The hydrophilic gel skeleton is hydroxypropyl methylcellulose, the moisturizer is glycerin, the transdermal penetration enhancer is azone, and the preservative is ethyl hydroxybenzoate.

[0102] The preparation method is similar to that of Example 1.

[0103] Comparative Example 3

[0104] The pharmaceutical composition patch of the present invention is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 42.9% of an external detumescent composition, 40.0% of a hydrophilic gel skeleton, 15.0% of a moisturizer, 2.0% of a transdermal penetration enhancer and 0.1% of a preservative.

[0105] The external detumescent composition is composed of 20 parts of mirabilite, 1.5 parts of borneol, 10 parts of schizonepeta volatile oil and 5 parts of angelica volatile oil by weight.

[0106] The hydrophilic gel skeleton is hydroxypropyl methylcellulose, the moisturizer is glycerin, the transdermal penetration enhancer is azone, and the preservative is ethyl hydroxybenzoate.

[0107] The preparation method is similar to that of Example 1.

[0108] Comparative Example 4

[0109] Compared with Example 1, the difference is that the hydrophilic gel skeleton is different, that is, the hydrophilic gel skeleton is carbomer, and the other components and amounts are the same.

[0110] The preparation method is similar to that of Example 1.

[0111] Efficacy Example 1 Anti-swelling and anti-inflammatory effects of the Chinese medicine composition of the present invention on adjuvant arthritis rats

[0112] 1. Establishment of rat model of joint swelling

[0113] 64 male SPF SD rats, weighing 180-220g, were given free access to water and diet. The room temperature in the feeding room was maintained at 25±1°C, and the light-dark cycle was 12h. After 1 week of adaptive feeding, 8 rats were randomly selected as the normal control group according to body weight, and the remaining rats were the modeling group. The normal control group rats were injected with 0.1mL of normal saline into the plantar of the hind foot, and the remaining groups of rats were injected with 0.1mL of complete Freund's adjuvant into the plantar of the hind foot. Redness and swelling of the hind foot were visible 1h after injection, indicating that the modeling was successful. The rats with successful modeling were randomly divided into the model control group, the embodiment 1 group, the embodiment 2 group, the comparative example 1 group, the comparative example 2 group, the comparative example 3 group, and the comparative example 4 group, with 8 rats in each group. The normal control group and the model control group rats were smeared with equal volumes of solvent on their feet, and the remaining groups of rats were smeared with corresponding drugs on their feet, once a day. Continuous 21d.

[0114] 2. Model observation and indicator detection

[0115] 2.1 Rat foot volume measurement

[0116] During the intervention period, the paw volume of rats was measured once every 7 days using a toe volume meter.

[0117] Foot swelling degree = (toe volume after modeling - toe volume before modeling) / toe volume before modeling × 100%

[0118] 2.2 Specimen Collection

[0119] After the last administration, the rats in each group were fasted for 8 hours and then anesthetized. Blood was collected from the abdominal aorta and centrifuged at 3000 rpm for 10 minutes. Serum was collected and stored at -80°C for detection by the kit.

[0120] 2.3 Detection of rat cytokines

[0121] Take the serum samples collected under "2.2" and detect the serum cytokines TNF-α, IL-1β, IL-6, and IL-10 of rats in each group according to the method in the kit instructions.

[0122] 3. Statistical methods

[0123] SPSS 22.0 software was used for data processing, and the data were expressed as mean ± standard deviation. The data of each group were subjected to normal distribution test and variance homogeneity test, and the inter-group comparison was performed with one-way analysis of variance, with P < 0.05 as the difference being statistically significant.

[0124] 4. Experimental Results

[0125] 4.1 Effect of the Chinese medicine composition of the present invention on foot swelling in rats of each group

[0126] Compared with the normal control group, the foot swelling of rats in the model control group was significantly increased. Compared with the model control group, the foot swelling of rats in Example 1 and Example 2 groups was significantly reduced. The effect of improving foot swelling in Example 1 group was better than that in the control group. Figure 1 .

[0127] 4.2 Effect of the Chinese medicine composition of the present invention on serum TNF-α in rats of each group

[0128] Compared with the normal control group, the serum TNF-α of the rats in the model control group was significantly increased. Compared with the model control group, the serum TNF-α of the rats in Example 1 and Example 2 groups was significantly reduced. The effect of improving serum TNF-α in Example 1 group was better than that in the control group. Figure 2 .

[0129] 4.3 Effect of the Chinese medicine composition of the present invention on serum IL-1β in rats of each group

[0130] Compared with the normal control group, the serum IL-1β of the rats in the model control group was significantly increased. Compared with the model control group, the serum IL-1β of the rats in Example 1 and Example 2 groups was significantly reduced. The effect of improving serum IL-1β in Example 1 group was better than that in the control group. Figure 3 .

[0131] 4.4 Effect of the Chinese medicine composition of the present invention on serum IL-6 in rats of each group

[0132] Compared with the normal control group, the serum IL-6 of the rats in the model control group was significantly increased. Compared with the model control group, the serum IL-6 of the rats in Example 1 and Example 2 groups was significantly reduced. The effect of improving serum IL-6 in Example 1 group was better than that in the control group. Figure 4 .

[0133] 4.5 Effect of the Chinese medicine composition of the present invention on serum IL-10 in rats of each group

[0134] Compared with the normal control group, the serum IL-10 of the rats in the model control group was significantly reduced. Compared with the model control group, the serum IL-10 of the rats in Example 1 and Example 2 groups was significantly increased. The effect of improving serum IL-10 in Example 1 group was better than that in the control group. Figure 5 .

[0135] In the adjuvant arthritis rat model, tuberculosis bacteria, as external antigens, induce immune responses in the body's tissues, thereby stimulating a series of inflammatory responses and increased capillary permeability, resulting in local tissue redness and swelling. Therefore, inhibiting the outbreak of inflammatory responses can effectively alleviate tissue redness and swelling.

[0136] The Chinese medicine composition of the present invention significantly reduces the degree of foot swelling and the levels of inflammatory cytokines such as serum TNF-α, IL-1β, IL-6, etc. in arthritis model rats, and increases the level of serum anti-inflammatory factor IL-10, thereby playing an anti-inflammatory and detumescent role. The therapeutic effect of the Chinese medicine composition Example 1 group on arthritis foot swelling is better than that of the other groups.

[0137] Clinical example: Observation on the clinical efficacy of the topical detumescent drug of the present invention on acute ankle sprain

[0138] 1. General Information

[0139] 124 patients with acute ankle sprains in our hospital were selected and met the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases". The inclusion criteria were sprains with swelling and pain in the ankle joint, difficulty in movement; no damage to the skin of the injured area; X-rays to exclude fractures and dislocations; injury time less than 24 hours; no allergy to the applied drugs. There were 78 male patients and 46 female patients.

[0140] The patients were randomly divided into control group, experimental group 1, experimental group 2 and experimental group 3, with 31 subjects in each group. Among them, there were 20 males and 11 females in the control group, with an average age of (30.5±12.7) years old; there were 19 males and 9 females in experimental group 1, with an average age of (33.1±10.2) years old; there were 21 males and 10 females in experimental group 2, with an average age of (31.8±9.2) years old; there were 18 males and 13 females in experimental group 3, with an average age of (34.9±11.6) years old.

[0141] There was no statistical difference in the general information of patients in each group (P>0.05), and they were comparable.

[0142] 2. Treatment Methods

[0143] The control group used ice to compress the injured part. The test group 1 applied Example 1 to the patient's part, the test group 2 applied Example 2 to the patient's part, and the test group 3 applied Comparative Example 1 to the patient's part 2-3 times a day, and the recovery was checked after three days. Each group treated the red and swollen part within 24 hours after the injury and fixed it with a bandage.

[0144] 3. Observation indicators

[0145] Cure criteria: Swelling and pain disappear, and the patient can walk freely. Significantly effective criteria: Slight swelling and pain are not obvious, and walking is slightly painful. Effective criteria: Swelling and pain are reduced, and walking becomes laborious. Ineffective criteria: Swelling and pain are not relieved, and the patient cannot walk normally.

[0146] Total effective rate = (number of clinically cured + markedly effective + effective) cases / total number of cases × 100%.

[0147] 4. Statistical methods

[0148] SPSS 22.0 software was used for data processing. The data of each group were subjected to normal distribution test and variance homogeneity test, and the inter-group comparison was performed with one-way analysis of variance, with P < 0.05 as the difference being statistically significant.

[0149] 5. Comparison of clinical efficacy

[0150] Table 1 Comparison of clinical efficacy

[0151] Group Number of cases / case Total effective rate / % Control group 40 35.48 Test Group 1 40 93.54 Test Group 2 40 61.29 Experiment 3 groups 40 48.38

[0152] Depend on Figure 6 As shown in Table 1, the total effective rate of the control group was 35.48%, the total effective rate of the test group 1 was 93.54%, the total effective rate of the test group 2 was 61.29%, and the total effective rate of the test group 3 was 48.38%. The clinical efficacy of the test group 1 in reducing swelling and improving ankle sprains was significantly better than that of the control group, the test groups 2 and the test groups 3.

[0153] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A pharmaceutical composition for external use to reduce swelling, characterized in that: The external detumescent medicine composition consists of 18-22 parts of mirabilite, 0.05-0.15 parts of borneol, 5-15 parts of schizonepeta volatile oil and 3-7 parts of angelica volatile oil by weight.

2. The external detumescent pharmaceutical composition according to claim 1, characterized in that: The external detumescence medicine composition consists of 20 parts of mirabilite, 0.1 parts of borneol, 10 parts of schizonepeta volatile oil and 5 parts of angelica volatile oil by weight.

3. The external detumescent pharmaceutical composition according to any one of claims 1 or 2, characterized in that: The preparation method of the schizonepeta volatile oil is as follows: Schizonepeta decoction pieces are extracted by steam distillation or supercritical CO2 extraction to obtain volatile oil; The preparation method of the angelica volatile oil is as follows: the angelica slices are extracted by steam distillation or supercritical CO2 extraction to obtain the volatile oil.

4. The external detumescent pharmaceutical composition according to claim 3, characterized in that: The preparation method of the schizonepeta volatile oil is as follows: schizonepeta is crushed, extracted under the conditions of a pressure of 5 MPa and a temperature of 140° C., and the crushed schizonepeta is extracted in water for 30 minutes to obtain the schizonepeta volatile oil.

5. The external detumescent pharmaceutical composition according to claim 3, characterized in that: The preparation method of the angelica volatile oil is as follows: the angelica is crushed into 100 mesh fine powder, and extracted by supercritical extraction under the conditions of pressure 35MPa and temperature 45°C, the extraction time is 2h, the extraction number is 1, and the carbon dioxide flow rate is 30mL / min to obtain the angelica volatile oil.

6. The external detumescent pharmaceutical composition according to claim 1, characterized in that: The preparation method of the external medicine composition patch is as follows: grind and mix Glauber's salt and borneol according to weight, and then add schizonepeta volatile oil and angelica volatile oil to obtain the patch.

7. A patch of a pharmaceutical composition for external use to reduce swelling, characterized in that: The adhesive layer is composed of a backing layer, a drug-containing adhesive layer and a protective layer, wherein the drug-containing adhesive layer is composed of the following components in percentage by weight: 35%-45% of an external detumescent composition, 35%-45% of a hydrophilic gel skeleton, 10%-20% of a moisturizer, 0.5%-3% of a transdermal penetration enhancer and 0%-0.1% of a preservative; The external detumescent composition consists of 18-22 parts of mirabilite, 0.05-0.15 parts of borneol, 5-15 parts of schizonepeta volatile oil and 3-7 parts of angelica volatile oil by weight.

8. The patch of the external detumescent pharmaceutical composition according to claim 7, characterized in that: The hydrophilic gel skeleton is one or more of hydroxypropyl methylcellulose, hydroxyethyl cellulose or hydroxypropyl cellulose; the moisturizer is glycerol or polyethylene glycol 400; the transdermal penetration enhancer is azone or propylene glycol; and the preservative is ethylparaben or methylparaben.

9. The patch of the external detumescent pharmaceutical composition according to claim 7, characterized in that: The preparation method is as follows: (1) Grind and mix Glauber's salt and borneol by weight, then add volatile oil of Schizonepeta tenuifolia and volatile oil of Angelica sinensis to obtain an external medicine composition; (2) Add water to a hydrophilic gel skeleton, place for 24 hours to fully swell, mix on a water bath and add a moisturizer, stir and mix thoroughly to obtain a transparent and viscous hydrogel matrix; (3) Disperse the external medicine composition obtained in step (1) in the hydrogel matrix prepared in step (2), add a transdermal penetration enhancer and a preservative, mix evenly, remove bubbles by ultrasound, apply it on a backing layer while hot, and cover it with a protective layer after drying to obtain the external medicine composition.

10. Use of the external detumescent pharmaceutical composition according to claim 1 or the patch of the external detumescent pharmaceutical composition according to claim 7 in the preparation of detumescent drugs.

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