Compositions, liquid films and methods of making and use for treating rheumatoid arthritis

Abstract

The application discloses a composition for treating rheumatoid arthritis, a liquid film and a preparation method and application, relates to the technical field of traditional Chinese medicines, and comprises the following raw medicinal materials in parts by weight: Baiji 15-25 parts, Chuanqiong 25-35 parts, Cisquifeng 25-35 parts, Fangji 25-35 parts, Qingfengteng 25-35 parts, Rhizoma Curcumae 25-35 parts, Jixueteng 25-35 parts, Yansu 25-35 parts, Mody 15-25 parts, Cangshu 25-35 parts, Duhuo 15-25 parts, Qianghuo 15-25 parts, Shengjiang 25-35 parts, Baijiezi 20-30 parts, Maowuzao 25-35 parts, Wugong 10-20 parts, Eshu 15-25 parts, Weilingxian 25-35 parts, Zhizheng 15-25 parts and Yousong 20-30 parts; and the application can solve the technical problem of gastrointestinal discomfort and allergic adverse reactions caused by rheumatoid arthritis drugs.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a composition, liquid membrane, preparation method, and application for treating rheumatoid arthritis. Background Technology

[0002] Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by joint inflammation, pain, swelling, and functional impairment. It typically begins in the small joints of the proximal interphalangeal joints of the fingers, metacarpophalangeal joints, and wrists, gradually affecting multiple joints symmetrically. Ultimately, it presents with typical inflammatory joint changes, such as prolonged morning stiffness, swelling, and pain, which can lead to severe joint deformities.

[0003] Currently, drug therapy is the core treatment for rheumatoid arthritis. On the one hand, nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control pain and reduce inflammation, while antirheumatic drugs improve the condition. However, adverse reactions may occur during medication, such as gastrointestinal discomfort, immune system suppression, and infection. On the other hand, traditional Chinese medicine reagents can be used externally to improve the condition and relieve pain. However, external application may lead to adverse reactions, such as skin allergies, skin ulcers, fever, or infection. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the purpose of this invention is to provide a composition, liquid membrane, preparation method and application for treating rheumatoid arthritis, aiming to solve the problems of gastrointestinal discomfort and allergic adverse reactions caused by existing rheumatoid arthritis drugs.

[0005] A first aspect of the present invention is to provide a composition for treating rheumatoid arthritis, the composition comprising, by weight, the following active pharmaceutical ingredient:

[0006] Angelica dahurica 15-25 parts, Ligusticum chuanxiong 25-35 parts, Tribulus terrestris 25-35 parts, Stephania tetrandra 25-35 parts, Sinomenium acutum 25-35 parts, Curcuma longa 25-35 parts, Spatholobus suberectus 25-35 parts, Corydalis yanhusuo 25-35 parts, Commiphora myrrha 15-25 parts, Atractylodes lancea 25-35 parts, Angelica pubescens 15-25 parts, Notopterygium incisum 15-25 parts, fresh ginger 25-35 parts, Sinapis alba 20-30 parts, Uncaria rhynchophylla 25-35 parts, Scolopendra subspinipes 10-20 parts, Curcuma zedoaria 15-25 parts, Clematis chinensis 25-35 parts, processed Aconitum carmichaelii 15-25 parts, Pinus tabuliformis 20-30 parts.

[0007] Compared with the prior art, the beneficial effects of the present invention are as follows: the composition for treating rheumatoid arthritis provided by the present invention alleviates the pain symptoms of rheumatoid arthritis and reduces the occurrence of adverse reactions. Specifically, the composition comprises the following raw materials in parts by weight: Angelica dahurica 15-25 parts, Ligusticum chuanxiong 25-35 parts, Tribulus terrestris 25-35 parts, Stephania tetrandra 25-35 parts, Sinomenium acutum 25-35 parts, Curcuma longa 25-35 parts, Spatholobus suberectus 25-35 parts, Corydalis yanhusuo 25-35 parts, Commiphora myrrha 15-25 parts, Atractylodes lancea 25-35 parts, Angelica pubescens 15-25 parts, Notopterygium incisum 15-25 parts, fresh ginger 25-35 parts, and Sinapis alba 25-35 parts. The formula consists of 20-30 parts of *Illicium verum*, 25-35 parts of *Cephalotaxus fortunei*, 10-20 parts of *Scolopendra subspinipes*, 15-25 parts of *Curcuma zedoaria*, 25-35 parts of *Clematis chinensis*, 15-25 parts of processed *Aconitum carmichaelii*, and 20-30 parts of *Pinus tabuliformis*. Through the combination and compatibility of these various raw materials, it possesses the characteristics of dispelling wind, cold, and dampness, promoting blood circulation, unblocking meridians, and relieving pain, thereby achieving the effect of alleviating rheumatoid arthritis. Each raw material is pungent and warm in nature, and the combined formula has anti-allergic effects. No adverse reactions have been observed during long-term clinical use, unlike the common adverse reactions of traditional external application Chinese medicines. This solves the technical problem of gastrointestinal discomfort and allergic reactions caused by rheumatoid arthritis medications.

[0008] According to one aspect of the above technical solution, the weight ratio of the Stephania tetrandra, the Tribulus terrestris and the Atractylodes lancea is 1:(0.8-1.2):(0.8-1.2).

[0009] According to one aspect of the above technical solution, the raw materials include the following parts by weight: 20 parts Angelica dahurica, 30 parts Ligusticum chuanxiong, 30 parts Tribulus terrestris, 30 parts Stephania tetrandra, 30 parts Sinomenium acutum, 30 parts Curcuma longa, 30 parts Spatholobus suberectus, 30 parts Corydalis yanhusuo, 20 parts Commiphora myrrha, 30 parts Atractylodes lancea, 20 parts Angelica pubescens, 20 parts Notopterygium incisum, 30 parts fresh ginger, 25 parts white mustard seed, 30 parts Uncaria rhynchophylla, 15 parts Scolopendra subspinipes, 20 parts Curcuma zedoaria, 30 parts Clematis chinensis, 20 parts processed Aconitum carmichaelii, and 25 parts Pinus tabuliformis.

[0010] A second aspect of the present invention is to provide a liquid membrane for treating rheumatoid arthritis, the liquid membrane comprising the above-described composition for treating rheumatoid arthritis, the liquid membrane further comprising a film-forming agent, a penetration enhancer, and a plasticizer.

[0011] According to one aspect of the above technical solution, the film-forming agent accounts for 6%-15% by mass, the penetration enhancer accounts for 5%-20% by mass, the plasticizer accounts for 1%-10% by mass, and the active pharmaceutical ingredient accounts for 10%-50% by mass.

[0012] According to one aspect of the above technical solution, the film-forming agent includes polyvinyl butyral and polyvinyl alcohol, the penetration enhancer includes propylene glycol or dodecyl N,N-dimethylaminoisopropionate or dodecyl N,N-dimethylaminoacetic acid, and the plasticizer includes glycerol and polyethylene glycol.

[0013] According to one aspect of the above technical solution, the mass ratio of polyvinyl butyral to polyvinyl alcohol is 1:(1-3), and the mass ratio of glycerol to polyethylene glycol is 1:(0.5-1).

[0014] A third aspect of the present invention is to provide a method for preparing a liquid membrane for treating rheumatoid arthritis, the method comprising:

[0015] The active pharmaceutical ingredient is added to an ethanol solution of a first preset concentration at a preset solid-liquid ratio, and the mixture is refluxed and extracted twice. The filtrates are combined and concentrated under reduced pressure to obtain the drug extract.

[0016] Add the film-forming agent to a predetermined volume of deionized water, heat and stir to mix evenly, then add the plasticizer and mix evenly to obtain the film-forming solution;

[0017] The drug extract is added dropwise to the film-forming solution with stirring to dissolve it. Then, a penetration enhancer is added and the mixture is stirred until homogeneous to obtain the liquid film.

[0018] According to one aspect of the above technical solution, the preset solid-liquid ratio is 1:(8-12), the first preset concentration is 60%-90%, and the preset volume is 100ml.

[0019] A third aspect of the present invention is to provide an application of the liquid membrane for treating rheumatoid arthritis as described above in the treatment of rheumatoid arthritis. Attached Figure Description

[0020] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0021] Figure 1 This is a flowchart of the method for preparing the liquid membrane for treating rheumatoid arthritis according to the present invention. Detailed Implementation

[0022] To make the objectives, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Several embodiments of the present invention are shown in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that the disclosure of the present invention will be more thorough and complete.

[0023] It should be noted that when an element is referred to as being "fixed to" another element, it can be directly on the other element or there may be an intervening element. When an element is considered to be "connected" to another element, it can be directly connected to the other element or there may be an intervening element. The terms "vertical," "horizontal," "left," "right," "upper," "lower," and similar expressions used herein are for illustrative purposes only and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as limiting the invention.

[0024] In this invention, unless otherwise expressly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances. The term "and / or" as used herein includes any and all combinations of one or more of the related listed items.

[0025] This invention provides a composition for treating rheumatoid arthritis, the composition comprising the following parts by weight of active pharmaceutical ingredient:

[0026] Angelica dahurica 15-25 parts, Ligusticum chuanxiong 25-35 parts, Tribulus terrestris 25-35 parts, Stephania tetrandra 25-35 parts, Sinomenium acutum 25-35 parts, Curcuma longa 25-35 parts, Spatholobus suberectus 25-35 parts, Corydalis yanhusuo 25-35 parts, Commiphora myrrha 15-25 parts, Atractylodes lancea 25-35 parts, Angelica pubescens 15-25 parts, Notopterygium incisum 15-25 parts, fresh ginger 25-35 parts, Sinapis alba 20-30 parts, Uncaria rhynchophylla 25-35 parts, Scolopendra subspinipes 10-20 parts, Curcuma zedoaria 15-25 parts, Clematis chinensis 25-35 parts, processed Aconitum carmichaelii 15-25 parts, Pinus tabuliformis 20-30 parts.

[0027] Angelica dahurica: Enters the stomach, large intestine, and lung meridians. It is pungent and warm in nature. It dispels wind and dampness, clears the nasal passages and relieves pain, reduces swelling and drains pus. It is used for colds with headache, supraorbital neuralgia, nasal congestion, sinusitis, toothache, leukorrhea, and sores and swelling.

[0028] Preferably, the amount of Angelica dahurica is 15-25 parts, for example, it can be 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0029] Chuanxiong (Ligusticum striatum): Enters the liver, gallbladder, and pericardium meridians. It is pungent and warm in nature. It invigorates blood circulation, promotes qi circulation, dispels wind, and relieves pain. It is used for irregular menstruation, amenorrhea, dysmenorrhea, abdominal masses and pain, chest and rib pain, traumatic swelling and pain, headache, and rheumatic pain.

[0030] Preferably, the amount of Ligusticum chuanxiong is 25-35 parts, for example, it can be 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0031] Tribulus terrestris: Enters the Liver, Lung, Kidney, and Heart meridians. Taste and nature: Bitter and pungent; neutral. Functions: Calms the Liver; relieves depression; dispels wind and improves vision. Mainly used for headaches; dizziness; chest and rib pain; breast pain; blocked milk ducts; amenorrhea; red and pterygium; urticaria and itching; vitiligo; sores and carbuncles; scrofula.

[0032] Preferably, the amount of Tribulus terrestris is 25-35 parts, for example, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0033] Fangji (Stephania tetrandra): Enters the bladder and lung meridians. It is bitter and cold in nature. It promotes diuresis and reduces swelling, dispels wind and relieves pain. It is used for edema, beriberi, difficulty urinating, eczema, sores, rheumatic pain, and hypertension.

[0034] Preferably, the amount of Fangji is 25-35 parts, for example, it can be 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0035] *Sinomenium acutum*: Enters the liver and spleen meridians. Its flavor is bitter and pungent, and its nature is neutral. It dispels wind and dampness, unblocks the meridians, and promotes urination. It is used for rheumatic pain, joint swelling, numbness, and itching.

[0036] Preferably, the amount of *Sinomenium acutum* is 25-35 parts, for example, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0037] Turmeric: Enters the spleen and liver meridians. It is pungent, bitter, and warm in nature. It breaks up blood stasis, promotes qi circulation, unblocks meridians, and relieves pain. It is used for stabbing pain in the chest and hypochondrium, amenorrhea, abdominal masses, rheumatic shoulder and arm pain, and swelling and pain from falls and injuries.

[0038] Preferably, the amount of turmeric is 25-35 parts, for example, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0039] Chicken Blood Vine: Enters the Liver and Kidney meridians. Its properties are bitter, sweet, and warm. It nourishes blood, invigorates blood circulation, and unblocks the meridians. It is used for irregular menstruation, blood deficiency and chlorosis, numbness and paralysis, and rheumatic pain.

[0040] Preferably, the amount of chicken blood vine is 25-35 parts, for example, it can be 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0041] Corydalis Rhizome: Enters the Liver and Spleen meridians. It is pungent, bitter, and warm in nature. It invigorates blood circulation, regulates qi, and relieves pain. It is used for chest and rib pain, abdominal pain, amenorrhea, dysmenorrhea, postpartum blood stasis, and traumatic swelling and pain.

[0042] Preferably, the amount of Corydalis is 25-35 parts, for example, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0043] Myrrh: Enters the liver, spleen, heart, and kidney meridians. Taste and nature: bitter; neutral. Invigorates blood circulation and relieves pain; reduces swelling and promotes tissue regeneration. Mainly used for chest and abdominal pain due to blood stasis; dysmenorrhea; amenorrhea; abdominal masses; traumatic injuries; carbuncles and sores; intestinal abscesses; and red, swollen, and painful eyes.

[0044] Preferably, the amount of myrrh is 15-25 parts, for example, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0045] Atractylodes lancea: Enters the spleen, stomach, and liver meridians. It is pungent, bitter, and warm in nature. It dries dampness, strengthens the spleen, dispels wind and cold, and improves eyesight. It is used for abdominal distension, diarrhea, edema, beriberi, rheumatic pain, common cold due to wind-cold, and night blindness.

[0046] Preferably, the Atractylodes lancea is used in 25-35 parts, for example, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0047] Angelica pubescens: Enters the kidney and bladder meridians. It is pungent, bitter, and slightly warm in nature. It dispels wind and dampness, relieves pain and numbness. It is used for wind-cold-dampness arthralgia, lower back and knee pain, and headache due to latent wind in the Shaoyin meridian.

[0048] Preferably, the amount of Angelica pubescens is 15-25 parts, for example, it can be 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0049] Notopterygium root: Enters the bladder and kidney meridians. It is pungent, bitter, and warm in nature. It dispels cold, wind, dampness, and pain. It is used for headaches due to wind-cold, rheumatic pain, and shoulder and back pain.

[0050] Preferably, the amount of Notopterygium root is 15-25 parts, for example, it can be 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0051] Ginger: Enters the lung, spleen, and stomach meridians. It is pungent and slightly warm in nature. It relieves exterior syndromes and dispels cold, warms the middle jiao and stops vomiting, resolves phlegm and stops coughing. It is used for common cold due to wind-cold, vomiting due to stomach cold, and cough with phlegm due to cold.

[0052] Preferably, the amount of ginger is 25-35 parts, for example, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0053] White mustard seed: Enters the lung, liver, spleen, stomach, and pericardium meridians. It is pungent and warm in nature. It resolves phlegm and eliminates fluid retention; disperses nodules and reduces swelling. It is mainly used for cough and asthma with excessive phlegm; chest fullness and hypochondriac pain; numbness of limbs; joint swelling and pain; phlegm-dampness accumulation; and carbuncles and boils.

[0054] Preferably, the amount of white mustard seeds is 20-30 parts, for example, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts or 30 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0055] Cat's Claw Herb: Enters the Liver and Lung meridians. Its properties are sweet and pungent; warm; neutral. It detoxifies, resolves phlegm, and dissipates nodules. It is used to treat scrofula, tuberculosis, pharyngitis, boils, snake bites, malaria, migraines, and toothache.

[0056] Preferably, the amount of cat's claw grass is 25-35 parts, for example, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0057] Centipede: Enters the Liver Meridian. It is pungent and warm in nature; poisonous. It calms wind and relieves spasms, dissipates toxins and nodules, unblocks meridians and relieves pain. Used for infantile convulsions, spasms, facial paralysis due to stroke, hemiplegia, tetanus, stubborn rheumatism, sores, scrofula, and snake bites.

[0058] Preferably, the number of centipedes is 10-20 parts, for example, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0059] Curcuma zedoaria: Enters the liver and spleen meridians. It is pungent and bitter in flavor and warm in nature. It promotes qi circulation and breaks up blood stasis; eliminates stagnation and relieves pain. It is used to treat heart pain due to blood stasis; food stagnation; abdominal distension and pain; amenorrhea due to blood stasis; dysmenorrhea; abdominal masses; and traumatic injuries.

[0060] Preferably, the amount of Curcuma zedoaria is 15-25 parts, for example, it can be 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0061] Clematis chinensis: Enters the Bladder Meridian. Its properties are pungent, salty, and warm. It dispels wind and dampness, unblocks the meridians, and relieves pain. It is used for rheumatic pain, numbness of limbs, muscle contractures, difficulty in flexion and extension, and bone obstruction in the throat.

[0062] Preferably, the amount of Clematis chinensis is 25-35 parts, for example, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, 30 parts, 31 parts, 32 parts, 33 parts, 34 parts or 35 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0063] Prepared Aconitum carmichaelii: Enters the Heart, Liver, Spleen, and Kidney meridians. Its properties are pungent, bitter, hot, and highly toxic. It dispels wind and dampness, warms the meridians, disperses cold, and relieves pain. It is used to treat wind-cold-dampness arthralgia, joint pain, numbness of limbs, hemiplegia, headache, cold pain in the heart and abdomen, hernia pain due to cold, traumatic injuries and bruises, carbuncles and boils; and can also be used for anesthesia and pain relief.

[0064] Preferably, the amount of processed Aconitum carmichaelii is 15-25 parts, for example, it can be 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0065] Pine resin: Enters the liver and kidney meridians; bitter and warm in nature. It dispels wind, dries dampness, relaxes muscles and tendons, and unblocks the meridians. It treats arthralgia, muscle spasms, beriberi, rheumatism, and traumatic injuries with blood stasis.

[0066] Preferably, the amount of pine resin is 20-30 parts, for example, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts or 30 parts, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0067] The composition of the present invention for treating rheumatoid arthritis is mainly used to treat wind-cold-dampness syndrome and phlegm-blood stasis syndrome, the basic pathogenesis of which is wind-dampness, phlegm-blood stasis, and obstruction of the meridians.

[0068] Furthermore, the principal herbs, primarily used to dispel wind and dampness, unblock meridians, nourish blood, and promote blood circulation, include: Fangji (Stephania tetrandra), Qingfengteng (Sinomenium acutum), Cangzhu (Atractylodes lancea), Chuanxiong (Ligusticum striatum), Cijili (Tribulus terrestris), Jixueteng (Spatholobus suberectus), and Yanhusuo (Corydalis yanhusuo). Among these, Fangji promotes diuresis and reduces swelling, dispels wind and relieves pain; Qingfengteng dispels wind and dampness, unblocks meridians, promotes urination, and enters the meridians, effectively treating wind-related diseases, thus treating all types of joint pain and numbness; Cangzhu (Atractylodes lancea) eliminates dampness and strengthens the spleen, relieving dampness-related body pain; Chuanxiong (Ligusticum striatum) invigorates blood circulation, promotes qi circulation, dispels wind and relieves pain, enters the blood level, and can dispel all wind and regulate all qi, making it a qi-regulating herb in the blood. Cijili (Tribulus terrestris): It is effective in dispersing and breaking up pathogens, specifically entering the lungs and liver, clearing stagnation in the lungs and relieving liver stasis, thus treating wind-related arthralgia, eye diseases, mastitis, and other ailments. It is a warm, bitter, pungent, and dispersing herb, used for expelling pathogens, and has no tonifying effect. Jianghuang (Curcuma longa) breaks up blood stasis, promotes qi circulation, unblocks meridians, and relieves pain. Chicken blood vine nourishes blood, invigorates blood circulation, clears the meridians, removes blood stasis, generates new blood, and promotes smooth flow of blood through the meridians; Corydalis invigorates blood, promotes qi circulation, relieves pain, and its warming properties harmonize the body, allowing qi to flow smoothly; its pungent properties moisten and disperse, thus invigorating blood. The invigoration of blood and the flow of qi can resolve stagnation in the blood and qi, thus specifically treating various pains throughout the body.

[0069] The assistant herbs strengthen the dispelling of wind and dampness, unblocking of meridians, and resolving of phlegm. These assistant herbs include: pine resin, angelica pubescens, notopterygium incisum, processed aconite root, angelica dahurica, white mustard seed, cat's claw herb, and clematis chinensis. Among them, pine resin dispels wind, dries dampness, relaxes muscles, and unblocks meridians. It treats arthralgia, arthralgia with pain in the limbs as if they are falling apart, and is mainly used for chronic wind in the joints, wind deficiency, and foot numbness and pain. When roasted, it treats bone diseases and can dry dampness in the blood. It moves through the meridians, treats phlegm-fire, muscle and bone pain, dampness-induced weakness, and strengthens muscles and bones. Angelica pubescens dispels wind and dampness, unblocks numbness and relieves pain. It is good at moving blood, dispelling wind, dampness, and cold. For all wind-related symptoms, such as inability to bend or straighten the head and neck, inability to flex or straighten the waist and knees, or numbness and pain making walking difficult, these are all caused by wind and cold, or damage from summer heat and dampness; angelica pubescens, with its bitter, pungent, and warm properties, must be used to activate qi and blood and dispel cold pathogens. Angelica pubescens can clear the airways from the top of the head to the knees, dispersing latent wind in the kidney meridian. It is effective for neck and shoulder stiffness, hip and leg pain, and weakness and numbness in the feet, making movement impossible. It can treat wind, as wind overcomes dampness, and specifically dispels dampness. Angelica pubescens is bitter, pungent, and slightly warm; compared to Notopterygium incisum, its properties are milder. It effectively targets and treats wind-induced dryness in the Kidney meridian of the Foot-Shaoyin, where latent wind fails to emerge, causing headaches. Therefore, it is indispensable for treating dampness and numbness in the feet, preventing movement. It is also effective for toothache caused by wind-toxin, dizziness, and blurred vision, as it counteracts what it overcomes. Furthermore, where there is wind, there is always dampness; therefore, Notopterygium incisum treats dampness and wandering wind, while Angelica pubescens treats dampness and latent wind. Notopterygium incisum has a clear qi, promoting qi circulation and dispersing pathogenic factors from the Ying and Wei levels, while Angelica pubescens has a turbid qi, promoting blood circulation and warming and nourishing the Ying and Wei levels. Notopterygium incisum has the function of releasing exterior pathogens, while Angelica pubescens has the power to assist in releasing exterior pathogens. Notopterygium root dispels cold, wind, dampness, and pain, primarily treating pain throughout the body and joints, expelling wind-evil from the skin, eliminating both new and old wind-dampness, and purging necrotic tissue and carbuncles. Prepared Aconitum carmichaelii dispels wind and dampness; warms the meridians; dispels cold and relieves pain. Aconitum carmichaelii root is warm and drying, descending in nature, with a rapid and effective dispersing effect, opening the pores and expelling cold and dampness quickly. It is effective for arthritis, beriberi, cold hernia, cold accumulation, and abdominal pain. Angelica dahurica root is pungent and warm in flavor, with a strong aroma, and is most effective at drying dampness. It dispels wandering wind from the skin, relieves stomach cold, abdominal pain, and cold-dampness pain throughout the body. White mustard seed resolves phlegm and eliminates phlegm; disperses nodules and reduces swelling, relieving phlegm stagnation in the meridians, numbness of the limbs, joint swelling and pain, and damp phlegm accumulation. Uncaria rhynchophylla detoxifies; resolves phlegm and disperses nodules. Clematis chinensis dispels wind and dampness, unblocks the meridians and relieves pain; it is potent and rapid, moving without lingering, and opens the twelve meridians. It is used to treat wind, dampness, phlegm, and obstruction in the meridians, which can lead to gout, joint pain, swelling, or numbness.

[0070] The adjuvant herbs enhance the effects of the principal and assistant herbs in unblocking meridians and resolving blood stasis. These adjuvant herbs include: myrrh, centipede, turmeric, and ginger. Myrrh invigorates blood circulation, relieves pain, reduces swelling, and promotes tissue regeneration. Centipede calms wind, relieves spasms, dissipates toxins and nodules, unblocks meridians, and relieves pain. It is effective against stubborn rheumatism and arthralgia, as it has the fastest penetrating power, reaching both internal organs and external meridians, opening up any areas where qi and blood are stagnant. Turmeric promotes qi circulation, breaks up blood stasis, and relieves pain. Ginger warms the meridians, dispels cold, and relieves pain. Through the combination and compatibility of these various raw materials, the formula possesses the characteristics of dispelling wind, cold, and dampness, invigorating blood circulation, unblocking meridians, and relieving pain, thereby achieving the effect of alleviating rheumatoid arthritis. The individual raw materials are pungent and warm in nature, and the combined formula has anti-allergic effects. No adverse reactions have been observed during long-term clinical use, and common adverse reactions of traditional external application Chinese medicines such as skin allergies, skin ulcers, fever, and infection have not occurred.

[0071] It should be noted that the weight ratio of the aforementioned Fangji, the aforementioned Tribulus terrestris, and the aforementioned Atractylodes lancea is 1:(0.8-1.2):(0.8-1.2). This application, by adding Tribulus terrestris and Fangji, promotes blood circulation, dispels wind, relieves pain, stops itching, and prevents allergies. Atractylodes lancea also alleviates the side effects of Tribulus terrestris on the digestive system, specifically the stomach and spleen. The proportions of the three raw materials are adjusted to dispel wind, cold, and dampness, promote blood circulation, unblock meridians, and relieve pain, thereby alleviating the effects of rheumatoid arthritis.

[0072] In addition, the present invention also provides a liquid membrane for treating rheumatoid arthritis, comprising the above-mentioned composition for treating rheumatoid arthritis, wherein the liquid membrane further comprises a film-forming agent, a penetration enhancer, and a plasticizer. Through the combined action of the film-forming agent, the penetration enhancer, and the plasticizer, it has advantages such as high efficacy, strong adhesion, easy fixation, good appearance, resistance to detachment, no need for bandaging, strong drug penetration, and convenient use.

[0073] Preferably, the film-forming agent accounts for 6%-15% of the mass, the penetration enhancer accounts for 5%-20% of the mass, the plasticizer accounts for 1%-10% of the mass, and the active pharmaceutical ingredient accounts for 10%-50% of the mass. The film-forming agent shortens the film-forming time of the active pharmaceutical ingredient, prevents it from falling off, and improves air permeability, tensile strength, and elongation at break. The plasticizer effectively reduces hardness, and the penetration enhancer effectively increases the penetration amount of the active pharmaceutical ingredient, thereby improving efficacy.

[0074] Furthermore, the film-forming agent includes polyvinyl butyral and polyvinyl alcohol, wherein the mass ratio of polyvinyl butyral to polyvinyl alcohol is 1:(1-3). By mixing polyvinyl butyral and polyvinyl alcohol in a specific ratio, the complexing ability and polarity of hydroxyl groups are improved, the film-forming time is reduced, the viscosity is increased, and the film-forming quality is improved.

[0075] Furthermore, the plasticizer includes glycerol and polyethylene glycol, with a mass ratio of glycerol to polyethylene glycol of 1:(0.5-1). This will form relatively strong hydrogen bonds with the film-forming agent, further improving viscosity, tensile strength, and breaking strength, enhancing the adhesion of the active pharmaceutical ingredient, and facilitating the release and diffusion of the active pharmaceutical ingredient.

[0076] Furthermore, the penetration enhancer includes propylene glycol or dodecyl N,N-dimethylaminoisopropionate or dodecyl N,N-dimethylaminoacetic acid.

[0077] In addition, the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis, the method comprising steps S10-S12:

[0078] Step S10: Add the active pharmaceutical ingredient to an ethanol solution of a first preset concentration at a preset solid-liquid ratio, reflux and extract twice, combine the filtrates, concentrate under reduced pressure to obtain the drug extract;

[0079] Furthermore, the preset solid-liquid ratio is 1:(8-12), and the volume of the concentrate to the mass ratio of the raw drug is 1:1, that is, the concentration of the drug extract is 1g / ml.

[0080] Step S11: Add the film-forming agent to a preset volume of deionized water, heat and stir to mix evenly, add the plasticizer and mix evenly to obtain the film-forming solution;

[0081] Further, with a preset volume of 100ml, heat to 85℃-95℃ and stir until homogeneous.

[0082] Step S12: The drug extract is added dropwise to the film-forming solution with stirring to dissolve it. Then, a penetration enhancer is added and stirred until homogeneous to obtain the liquid film.

[0083] The volume of the added drug extract is 10ml-20ml.

[0084] It should be noted that the prepared liquid membrane has the characteristics of good film-forming properties, suitable membrane strength, good flexibility and adhesion.

[0085] Furthermore, the present invention also provides the application of the liquid membrane for treating rheumatoid arthritis as described above in the treatment of rheumatoid arthritis.

[0086] The present invention is further illustrated below with specific embodiments:

[0087] Example 1

[0088] The first embodiment of the present invention provides a composition for treating rheumatoid arthritis, the composition comprising the following parts by weight of active pharmaceutical ingredient:

[0089] Angelica dahurica 15-25 parts, Ligusticum chuanxiong 25-35 parts, Tribulus terrestris 25-35 parts, Stephania tetrandra 25-35 parts, Sinomenium acutum 25-35 parts, Curcuma longa 25-35 parts, Spatholobus suberectus 25-35 parts, Corydalis yanhusuo 25-35 parts, Commiphora myrrha 15-25 parts, Atractylodes lancea 25-35 parts, Angelica pubescens 15-25 parts, Notopterygium incisum 15-25 parts, fresh ginger 25-35 parts, Sinapis alba 20-30 parts, Uncaria rhynchophylla 25-35 parts, Scolopendra subspinipes 10-20 parts, Curcuma zedoaria 15-25 parts, Clematis chinensis 25-35 parts, processed Aconitum carmichaelii 15-25 parts, Pinus tabuliformis 20-30 parts.

[0090] Among them, Angelica dahurica 20 parts, Ligusticum chuanxiong 30 parts, Tribulus terrestris 30 parts, Stephania tetrandra 30 parts, Sinomenium acutum 30 parts, Curcuma longa 30 parts, Spatholobus suberectus 30 parts, Corydalis yanhusuo 30 parts, Commiphora myrrha 20 parts, Atractylodes lancea 30 parts, Angelica pubescens 20 parts, Notopterygium incisum 20 parts, fresh ginger 30 parts, Sinapis alba 25 parts, Uncaria rhynchophylla 30 parts, Scolopendra subspinipes 15 parts, Curcuma zedoaria 20 parts, Clematis chinensis 30 parts, processed Aconitum carmichaelii 20 parts, and Pinus tabuliformis 25 parts.

[0091] In addition, this embodiment also provides a liquid membrane for treating rheumatoid arthritis, comprising the above-mentioned composition for treating rheumatoid arthritis, wherein the liquid membrane further comprises a film-forming agent, a penetration enhancer, and a plasticizer. The film-forming agent accounts for 8% by mass, the penetration enhancer accounts for 7% by mass, the plasticizer accounts for 2% by mass, and the active pharmaceutical ingredient accounts for 25% by mass.

[0092] Further, the film-forming agent includes polyvinyl butyral and polyvinyl alcohol, wherein the mass ratio of polyvinyl butyral to polyvinyl alcohol is 1:2; the plasticizer includes glycerol and polyethylene glycol, wherein the mass ratio of glycerol to polyethylene glycol is 1:0.8; and the penetration enhancer includes propylene glycol or dodecyl N,N-dimethylaminoisopropionate or dodecyl N,N-dimethylaminoacetic acid.

[0093] Specifically, the penetration enhancer is N,N-dimethylaminoisopropionic acid dodecyl ester.

[0094] Accordingly, this embodiment also provides a method for preparing a liquid membrane for treating rheumatoid arthritis, the method comprising steps S10-S12:

[0095] Step S10: Add the active pharmaceutical ingredient to an ethanol solution of a first preset concentration at a preset solid-liquid ratio, reflux and extract twice, combine the filtrates, concentrate under reduced pressure to obtain the drug extract;

[0096] Furthermore, the preset solid-liquid ratio is 1:10, the volume ratio of the concentrated extract to the mass ratio of the raw drug is 1:1, that is, the concentration of the drug in the drug extract is 1g / ml, and the first preset concentration is 80%.

[0097] Specifically, 100g of the raw drug is added to ten times the amount of 80% ethanol solution, and the mixture is refluxed and extracted twice. The filtrates are combined until the concentration of the drug in the extract is 1g / ml.

[0098] Step S11: Add the film-forming agent to a preset volume of deionized water, heat and stir to mix evenly, add the plasticizer and mix evenly to obtain the film-forming solution;

[0099] Further, with a preset volume of 100ml, heat to 85℃-95℃ and stir until homogeneous.

[0100] Specifically, 40g of film-forming agent is added to 100ml of deionized water, heated to 85℃-95℃ and stirred until homogeneous, and then 10g of plasticizer is added and mixed until homogeneous to obtain the film-forming solution.

[0101] Step S12: The drug extract is added dropwise to the film-forming solution with stirring to dissolve it. Then, a penetration enhancer is added and stirred until homogeneous to obtain the liquid film.

[0102] The volume of the added drug extract is 10ml-20ml.

[0103] Specifically, the drug extract is added dropwise to the film-forming solution with stirring to dissolve it. Then, 35g of penetration enhancer is added and stirred evenly. Finally, deionized water is added until the weight reaches 500g, thus obtaining the liquid membrane.

[0104] Example 2

[0105] A second embodiment of the present invention provides a composition for treating rheumatoid arthritis. The composition for treating rheumatoid arthritis in this embodiment differs from the composition for treating rheumatoid arthritis in the following ways:

[0106] Angelica dahurica 20 parts, Ligusticum chuanxiong 25 parts, Tribulus terrestris 35 parts, Stephania tetrandra 25 parts, Sinomenium acutum 35 parts, Curcuma longa 25 parts, Spatholobus suberectus 35 parts, Corydalis yanhusuo 35 parts, Commiphora myrrha 20 parts, Atractylodes lancea 25 parts, Angelica pubescens 20 parts, Notopterygium incisum 20 parts, fresh ginger 30 parts, white mustard seed 25 parts, Uncaria rhynchophylla 30 parts, Scolopendra subspinipes 15 parts, Curcuma zedoaria 20 parts, Clematis chinensis 30 parts, processed Aconitum carmichaelii 20 parts, Pinus tabuliformis 25 parts.

[0107] Example 3

[0108] A third embodiment of the present invention provides a composition for treating rheumatoid arthritis. The composition for treating rheumatoid arthritis in this embodiment differs from the composition for treating rheumatoid arthritis in the first embodiment in that:

[0109] Angelica dahurica 20 parts, Ligusticum chuanxiong 35 parts, Tribulus terrestris 25 parts, Stephania tetrandra 35 parts, Sinomenium acutum 25 parts, Curcuma longa 35 parts, Spatholobus suberectus 25 parts, Corydalis yanhusuo 25 parts, Commiphora myrrha 20 parts, Atractylodes lancea 35 parts, Angelica pubescens 20 parts, Notopterygium incisum 20 parts, fresh ginger 30 parts, white mustard seed 25 parts, Uncaria rhynchophylla 30 parts, Scolopendra subspinipes 15 parts, Curcuma zedoaria 20 parts, Clematis chinensis 30 parts, processed Aconitum carmichaelii 20 parts, Pinus tabuliformis 25 parts.

[0110] Example 4

[0111] The fourth embodiment of the present invention provides a composition for treating rheumatoid arthritis. The composition for treating rheumatoid arthritis in this embodiment differs from the composition for treating rheumatoid arthritis in the first embodiment in that:

[0112] Angelica dahurica 15 parts, Ligusticum chuanxiong 30 parts, Tribulus terrestris 30 parts, Stephania tetrandra 30 parts, Sinomenium acutum 30 parts, Curcuma longa 30 parts, Spatholobus suberectus 30 parts, Corydalis yanhusuo 30 parts, Commiphora myrrha 20 parts, Atractylodes lancea 30 parts, Angelica pubescens 25 parts, Notopterygium incisum 15 parts, fresh ginger 30 parts, white mustard seed 20 parts, Uncaria rhynchophylla 35 parts, Scolopendra subspinipes 15 parts, Curcuma zedoaria 20 parts, Clematis chinensis 25 parts, processed Aconitum carmichaelii 25 parts, Pinus tabuliformis 30 parts.

[0113] Example 5

[0114] The fifth embodiment of the present invention provides a composition for treating rheumatoid arthritis. The composition for treating rheumatoid arthritis in this embodiment differs from the composition for treating rheumatoid arthritis in the first embodiment in that:

[0115] Angelica dahurica 25 parts, Ligusticum chuanxiong 30 parts, Tribulus terrestris 30 parts, Stephania tetrandra 30 parts, Sinomenium acutum 30 parts, Curcuma longa 30 parts, Spatholobus suberectus 30 parts, Corydalis yanhusuo 30 parts, Commiphora myrrha 20 parts, Atractylodes lancea 30 parts, Angelica pubescens 15 parts, Notopterygium incisum 25 parts, fresh ginger 30 parts, white mustard seed 15 parts, Uncaria rhynchophylla 25 parts, Scolopendra subspinipes 15 parts, Curcuma zedoaria 20 parts, Clematis chinensis 35 parts, processed Aconitum carmichaelii 15 parts, Pinus tabuliformis 35 parts.

[0116] Example 6

[0117] The sixth embodiment of the present invention provides a composition for treating rheumatoid arthritis. The composition for treating rheumatoid arthritis in this embodiment differs from the composition for treating rheumatoid arthritis in the first embodiment in that:

[0118] Angelica dahurica 20 parts, Ligusticum chuanxiong 30 parts, Tribulus terrestris 30 parts, Stephania tetrandra 30 parts, Sinomenium acutum 30 parts, Curcuma longa 30 parts, Spatholobus suberectus 30 parts, Corydalis yanhusuo 30 parts, Commiphora myrrha 25 parts, Atractylodes lancea 30 parts, Angelica pubescens 20 parts, Notopterygium incisum 20 parts, fresh ginger 25 parts, white mustard seed 25 parts, Uncaria rhynchophylla 30 parts, Scolopendra subspinipes 10 parts, Curcuma zedoaria 25 parts, Clematis chinensis 30 parts, processed Aconitum carmichaelii 20 parts, Pinus tabuliformis 25 parts.

[0119] Example 7

[0120] The seventh embodiment of the present invention provides a composition for treating rheumatoid arthritis. The composition for treating rheumatoid arthritis in this embodiment differs from the composition for treating rheumatoid arthritis in the first embodiment in that:

[0121] Angelica dahurica 20 parts, Ligusticum chuanxiong 30 parts, Tribulus terrestris 30 parts, Stephania tetrandra 30 parts, Sinomenium acutum 30 parts, Curcuma longa 30 parts, Spatholobus suberectus 30 parts, Corydalis yanhusuo 30 parts, Commiphora myrrha 15 parts, Atractylodes lancea 30 parts, Angelica pubescens 20 parts, Notopterygium incisum 20 parts, fresh ginger 35 parts, white mustard seed 25 parts, Uncaria rhynchophylla 30 parts, Scolopendra subspinipes 20 parts, Curcuma zedoaria 15 parts, Clematis chinensis 30 parts, processed Aconitum carmichaelii 20 parts, Pinus tabuliformis 25 parts.

[0122] Example 8

[0123] The eighth embodiment of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0124] The mass ratio of polyvinyl butyral to polyvinyl alcohol is 1:1.

[0125] Example 9

[0126] The ninth embodiment of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0127] The mass ratio of polyvinyl butyral to polyvinyl alcohol is 1:3.

[0128] Example 10

[0129] The tenth embodiment of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing a liquid membrane for treating rheumatoid arthritis in this embodiment differs from other methods for preparing liquid membranes for treating rheumatoid arthritis in that:

[0130] The mass ratio of glycerol to polyethylene glycol is 1:0.5.

[0131] Example 11

[0132] The eleventh embodiment of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing a liquid membrane for treating rheumatoid arthritis in this embodiment differs from other methods for preparing liquid membranes for treating rheumatoid arthritis in that:

[0133] The mass ratio of glycerol to polyethylene glycol is 1:1.

[0134] Example 12

[0135] The twelfth embodiment of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0136] The penetration enhancer includes propylene glycol.

[0137] Example 13

[0138] The thirteenth embodiment of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0139] The penetration enhancer includes N,N-dimethylaminoacetic acid dodecyl ester.

[0140] Comparative Example 1

[0141] The first comparative example of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0142] The film-forming agent includes polyvinyl butyral.

[0143] Comparative Example 2

[0144] The second comparative example of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0145] The film-forming agent includes polyvinyl alcohol.

[0146] Comparative Example 3

[0147] The third comparative example of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0148] The plasticizer includes glycerin.

[0149] Comparative Example 4

[0150] The fourth comparative example of the present invention provides a method for preparing a liquid membrane for treating rheumatoid arthritis. The method for preparing the liquid membrane for treating rheumatoid arthritis in this embodiment differs from the method for preparing the liquid membrane for treating rheumatoid arthritis in the first embodiment in that:

[0151] The plasticizer includes polyethylene glycol.

[0152] animal experiments

[0153] Preparation of a rat arthritis model

[0154] After 3 days of acclimatization, 10 male rats were randomly selected as the normal control group. Male rats in the control group received a subcutaneous injection of 0.1 ml of physiological saline in the right hind paw. The remaining male rats were injected subcutaneously with 0.1 ml of Freund's complete adjuvant into the right hind paw to establish an adjuvant-induced arthritis model in SD rats. Swelling of the right hind paw was measured on day 10 after inflammation induction. Right hind paw swelling = right hind paw ankle joint circumference - left hind paw ankle joint circumference. Arthritis scoring criteria: Based on the degree and extent of joint redness and swelling, as well as the degree of joint swelling and deformity in rats with arthritis, a score of 0-4 was assigned; 0 points: normal; 1 point: erythema and mild swelling in the ankle joint; 2 points: erythema and mild swelling from the ankle to the metacarpophalangeal joint; 3 points: erythema and mild swelling from the ankle to the toe joint or erythema and moderate swelling from the ankle to the metacarpophalangeal joint; 4 points: erythema and severe swelling from the ankle to the toe joint. Each foot was scored separately, and the scores of all four limbs were added together to obtain the arthritis score, with a maximum score of 16 points per rat.

[0155] Male rats modeling arthritis were randomly divided into a control group and six groups (Example 1, Example 2, Example 3, Example 4, Example 5, and Example 6), with 10 rats in each group. The control group did not receive the liquid film, while the male rats in the Example 1, Example 2, Example 3, Example 4, Example 5, and Example 6 groups received the corresponding liquid film application twice daily, seven times a week, for 30 days as one treatment course.

[0156] Please refer to Table 1 below, which shows the parameters corresponding to Embodiments 1 to 7 of the present invention.

[0157] Table 1

[0158]

[0159] Based on the data from Examples 1 to 7, as well as the blank group and the control group, it can be seen that the liquid membrane with optimized formulation can effectively relieve rheumatoid arthritis.

[0160] Skin allergy test

[0161] Hair was removed from both sides of the back of each male rat, with each side measuring 3cm x 3cm. No skin damage was observed at the hair removal sites on each rat. The areas were then gently wiped clean with warm water. A sensitization contact experiment was conducted on the hairless skin on the left side of the male rats, with the left side designated as the treatment area and the right side as the control area. Ten male rats were used in each group. A liquid film was applied to the treatment area, while the control area was treated with a drug-free excipient, twice daily. Local skin allergic reactions, such as erythema and edema, were observed visually under natural light (the appearance of erythema or edema indicates a skin allergic reaction; a sensitization rate of less than 10% is considered no sensitization, 10%–30% as mild sensitization, 30%–60% as moderate sensitization, 60%–80% as severe sensitization, and over 90% as extreme sensitization). Simultaneously, the rats' mental state and systemic allergic reaction symptoms were closely monitored.

[0162] Please refer to Table 2 below, which shows the allergy tests of Examples 1 to 7 of the present invention.

[0163] Table 2

[0164]

[0165] Based on the data from Examples 1 to 7, it can be seen that the liquid film with optimized formulation can effectively reduce common adverse reactions of traditional external application of Chinese medicine, such as skin allergies, skin ulcers, fever, and infection.

[0166] Please refer to Table 3 below, which shows the performance parameters of the above-described embodiments 1, 8 to 13, and comparative examples 1 to 4 of the present invention.

[0167] Table 3

[0168]

[0169] Based on the data from Examples 1, 8 to 13, and Comparative Examples 1 to 4, it can be seen that the combined action of film-forming agents, penetration enhancers, and plasticizers can shorten film-forming time, increase tensile strength and elongation at break, and improve permeability, thereby enhancing drug efficacy.

[0170] Case examples:

[0171] The Visual Analogue Scale (VAS) uses a ruler to mark a horizontal line of 0-10 cm on paper, with scores in millimeters (mm). The scoring range is 0-100 mm, with higher scores indicating greater pain intensity. Patients mark points on the line according to their pain intensity, and the length of the mark is measured. Scoring criteria: 0-4 mm: no pain; 5-44 mm: mild pain; 45-75 mm: moderate pain; 75-100 mm: severe pain.

[0172] Case 1: Mr. Hu, male, 60 years old, was admitted to the hospital in March 2023 due to swelling and pain in both wrists, elbows, shoulders, knees, and ankles, and was diagnosed with rheumatoid arthritis. His VAS pain score was 80. After applying the liquid film of this invention for 7 days, the swelling and pain in all joints were relieved, and his VAS pain score was 30.

[0173] Case 2: Ms. Zhu, 54 years old, was admitted to the hospital in March 2023 due to swelling and pain in both wrists, shoulders, and knees, and was diagnosed with rheumatoid arthritis. Her VAS pain score was 82. After applying the liquid film of this invention for 16 days, the pain in all joints was relieved, and her VAS pain score was 25.

[0174] Case 3: Mr. Cao, male, 77 years old, was admitted to the hospital in May 2023 due to swelling and pain in the proximal interphalangeal joints of both hands, shoulders, elbows, wrists, knees, and ankles, and was diagnosed with rheumatoid arthritis. His VAS pain score was 92. After applying the liquid film of this invention for 20 days, the pain in each joint improved, and his VAS pain score was 15.

[0175] Case 4: Ms. Zhong, 82 years old, was admitted to the hospital in May 2023 due to swelling and pain in the shoulder, elbow, knee, ankle, and metacarpophalangeal joints, and was diagnosed with rheumatoid arthritis. Her VAS pain score was 97. After applying the liquid film of this invention for 9 days, the swelling and pain in all joints were relieved, and her VAS pain score was 25.

[0176] Case 5: Ms. Cai, 44 years old, was admitted to the hospital in June 2023 due to swelling and pain in the wrist, metacarpophalangeal joints, proximal interphalangeal joints, knee, and metatarsophalangeal joints, and was diagnosed with rheumatoid arthritis. Her VAS pain score was 88. After applying the liquid film of this invention for 7 days, the swelling and pain in all joints were relieved, and her VAS pain score was 30.

[0177] Case 6: Ms. Liu, 57 years old, was admitted to the hospital in July 2023 due to swelling and pain in both wrist joints and was diagnosed with rheumatoid arthritis. Her VAS pain score was 85. After applying the liquid film of this invention for 7 days, the swelling and pain in all joints were relieved, and her VAS pain score was 20.

[0178] In summary, the optimized liquid film formula can effectively relieve rheumatoid arthritis and reduce common adverse reactions of traditional topical Chinese medicine, such as skin allergies, skin ulcers, fever, and infection.

[0179] In the description of this specification, references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0180] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this patent should be determined by the appended claims.

Claims

1. A liquid membrane for treating rheumatoid arthritis, characterized in that, The liquid film comprises a composition for treating rheumatoid arthritis, a film-forming agent, a penetration enhancer, and a plasticizer. The film-forming agent comprises polyvinyl butyral and polyvinyl alcohol, wherein the mass ratio of polyvinyl butyral to polyvinyl alcohol is 1:(1-3). The composition comprises the following parts by weight of active pharmaceutical ingredients. composition: Angelica dahurica 15-25 parts, Ligusticum chuanxiong 25-35 parts, Tribulus terrestris 25-35 parts, Stephania tetrandra 25-35 parts, Sinomenium acutum 25-35 parts, Curcuma longa 25-35 parts, Spatholobus suberectus 25-35 parts, Corydalis yanhusuo 25-35 parts, Commiphora myrrha 15-25 parts, Atractylodes lancea 25-35 parts, Angelica pubescens 15-25 parts, Notopterygium incisum 15-25 parts, fresh ginger 25-35 parts, Sinapis alba 20-30 parts, Uncaria rhynchophylla 25-35 parts, Scolopendra subspinipes 10-20 parts, Curcuma zedoaria 15-25 parts, Clematis chinensis 25-35 parts, processed Aconitum carmichaelii 15-25 parts, Pinus tabuliformis 20-30 parts, the weight ratio of Stephania tetrandra, Tribulus terrestris and Atractylodes lancea is 1:(0.8-1.2):(0.8-1.2).

2. The liquid membrane for treating rheumatoid arthritis according to claim 1, characterized in that, The composition comprises the following raw materials in parts by weight: 20 parts Angelica dahurica, 30 parts Ligusticum chuanxiong, 30 parts Tribulus terrestris, 30 parts Stephania tetrandra, 30 parts Sinomenium acutum, 30 parts Curcuma longa, 30 parts Spatholobus suberectus, 30 parts Corydalis yanhusuo, 20 parts Commiphora myrrha, 30 parts Atractylodes lancea, 20 parts Angelica pubescens, 20 parts Notopterygium incisum, 30 parts fresh ginger, 25 parts Sinapis alba, 30 parts Uncaria rhynchophylla, 15 parts Scolopendra subspinipes, 20 parts Curcuma zedoaria, 30 parts Clematis chinensis, 20 parts processed Aconitum carmichaelii, and 25 parts Pinus tabuliformis.

3. The liquid membrane for treating rheumatoid arthritis according to claim 1, characterized in that, The film-forming agent accounts for 6%-15% of the mass, the penetration enhancer accounts for 5%-20% of the mass, the plasticizer accounts for 1%-10% of the mass, and the active pharmaceutical ingredient accounts for 10%-50% of the mass.

4. The liquid membrane for treating rheumatoid arthritis according to claim 3, characterized in that, The penetration enhancer includes propylene glycol or dodecyl N,N-dimethylaminoisopropionate or dodecyl N,N-dimethylaminoacetic acid, and the plasticizer includes glycerol and polyethylene glycol.

5. The liquid membrane for treating rheumatoid arthritis according to claim 4, characterized in that, The mass ratio of the glycerol to the polyethylene glycol is 1:(0.5-1).

6. A method for preparing a liquid membrane for treating rheumatoid arthritis, characterized in that, The preparation method is used to prepare the liquid membrane for treating rheumatoid arthritis according to any one of claims 1-5, the method comprising: Add the raw drug to a 60%-90% ethanol solution at a solid-liquid ratio of 1g:(8-12)mL, reflux and extract twice, combine the filtrates, concentrate under reduced pressure to obtain the drug extract; Add the film-forming agent to 100 mL of deionized water, heat and stir to mix evenly, then add the plasticizer and mix evenly to obtain the film-forming solution; The drug extract is added dropwise to the film-forming solution with stirring to dissolve it. Then, a penetration enhancer is added and the mixture is stirred until homogeneous to obtain the liquid film.

7. The use of a liquid membrane for treating rheumatoid arthritis as described in any one of claims 1-5 in the preparation of a medicament for treating rheumatoid arthritis.

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