A traditional Chinese medicine composition for acute gouty arthritis and a preparation method and application thereof

Abstract

The application provides a traditional Chinese medicine composition for acute gouty arthritis and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following components in percentage by mass: traditional Chinese medicine nano-phase state 5-30%, carbomer 940 1-5%, glycerol 3-12%, sodium hyaluronate 0.02-0.2%, 1,3-butanediol 1-6%, propylene glycol 1-8%, triethanolamine 1-8%, and the balance is distilled water; and the traditional Chinese medicine nano-phase state is made of cassia twig, red peony root, ephedra, anemarrhena, mirabilite, gardenia, and borneol. The traditional Chinese medicine composition has remarkable curative effect and is safe and reliable, solves the shortcomings of small drug loading and large odor of plaster, reduces the loss of functional components, strengthens the ability of the drug to penetrate the treatment site, and prolongs the release process of the drug.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and specifically relates to a traditional Chinese medicine composition for acute gouty arthritis, its preparation method, and its application. Background Technology

[0002] Gouty arthritis (GA) is a metabolic rheumatic disease caused by the precipitation of supersaturated urate from the blood or synovial fluid, forming crystals that deposit in the synovial bursae, synovium, cartilage, and other tissues of the joints. This leads to the chemotactic recruitment of leukocytes and the release of various inflammatory mediators, resulting in a local inflammatory response. Gouty arthritis is the most common type of inflammatory arthritis.

[0003] With rising economic levels, excessive purine intake and reduced physical activity have become the norm, leading to a year-on-year increase in the incidence of gouty arthritis, making it a common disease in developed regions. Global epidemiological surveys show that with economic development and improved living standards, the incidence and hospitalization rates of GA are increasing annually, and the disease is showing a trend towards affecting younger people.

[0004] Currently, Western medicine primarily treats acute gouty arthritis with colchicine, hormones, and nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce swelling and relieve pain, but this approach carries risks such as diarrhea, blood sugar fluctuations, and liver and kidney damage. Meanwhile, numerous studies have also utilized traditional Chinese medicine (TCM) to treat acute gouty arthritis, focusing on clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and reducing swelling and relieving pain. The main herbs used include rhubarb, scutellaria baicalensis, coptis chinensis, phellodendron chinense, honeysuckle, ampelopsis japonica, salvia miltiorrhiza, notoginseng, lithospermum erythrorhizon, safflower, angelica sinensis, trichosanthes kirilowii, and astragalus membranaceus. Currently, there are no commercially available targeted TCM topical preparations. Most studies primarily focus on clearing heat and detoxifying, lacking topical preparations specifically addressing the complex pattern of cold and heat in gout, and the internal stagnation of heat in the body.

[0005] Acute gouty arthritis manifests as redness, swelling, heat, and pain. Although the symptoms fall under the category of "heat arthritis" in traditional Chinese medicine, clinical findings show that many gout patients are triggered by exposure to cold pathogens, such as cold water, air conditioning, or consumption of cold foods like seafood. Upon closer examination, the generation of this heat toxicity is related to the long-term accumulation of cold and dampness, which transforms into heat. Under the induction of external factors such as cold pathogens, wind pathogens, and heat toxicity, the disease develops. Therefore, clinical treatment should combine cold and warm methods, focusing on clearing heat and expelling pathogens, and promoting blood circulation. This is combined with topical medications that have a rapid local effect and can exert their heat-clearing, swelling-reducing, and pain-relieving effects through the skin.

[0006] Current treatments for acute gouty arthritis primarily involve external physical therapy, such as herbal compresses and topical ointments. However, some ointments and tinctures are not specifically targeted at gouty arthritis. For example, diclofenac sodium is a nonsteroidal anti-inflammatory drug (NSAID) with poor specificity, and long-term use can lead to nephrotoxicity. Therefore, it is necessary to further develop drugs with proven efficacy, minimal side effects, and high safety for the treatment of acute gouty arthritis. Summary of the Invention

[0007] To overcome the shortcomings of existing technologies, this invention provides a traditional Chinese medicine composition for acute gouty arthritis, which is characterized by significant efficacy, safety, reliability, and ease of use. Specifically, by applying the traditional Chinese medicine composition of this invention topically, patients with acute gouty arthritis can avoid a series of adverse reactions caused by oral medications, thus preventing side effects. Simultaneously, this invention also provides a method for preparing the aforementioned traditional Chinese medicine composition for acute gouty arthritis. Through research on formulation processes, the shortcomings of small drug loading and strong odor in plasters are overcome, the loss of active ingredients is reduced, the ability of the drug to penetrate the treatment site is enhanced, and the drug release process is prolonged.

[0008] This invention is implemented through the following aspects.

[0009] In a first aspect, a traditional Chinese medicine composition for acute gouty arthritis is provided, the composition comprising the following components by weight percentage: 5-30% traditional Chinese medicine nano-phase material, 1-5% carbomer 940, 3-12% glycerin, 0.02-0.2% sodium hyaluronate, 1-6% 1,3-butanediol, 1-8% propylene glycol, 1-8% triethanolamine, and the balance being distilled water;

[0010] The traditional Chinese medicine nanophase material is made from the following raw materials in parts by weight: 0.5-8 parts of cinnamon twig, 0.5-8 parts of red peony root, 1-5 parts of ephedra, 0.5-8 parts of anemarrhena rhizome, 2-15 parts of mirabilite, 1-10 parts of gardenia fruit, and 1-8 parts of borneol.

[0011] The raw materials of the traditional Chinese medicine composition of this invention have the following sources and functions:

[0012] Cinnamon twig: The dried tender twig of the cinnamon tree (Cinnamomum cassia), a plant in the Lauraceae family. It is pungent, sweet, and warm in nature, possessing various effects such as inducing sweating and relieving muscle tension, and warming and unblocking the meridians. The *Shennong Bencao Jing* records that it can "benefit the joints," and the *Mingyi Bielu* states that it can invigorate the meridians, exerting the effects of warming and unblocking the meridians, promoting blood circulation, and relieving pain. Cinnamon twig has the nature of wind and wood, promoting the flow of qi in the body while soothing the liver and relieving stagnation, and promoting the transformation of dampness in the spleen. Therefore, it also has the effect of soothing the liver and invigorating the spleen. When combined with red peony root, it can unblock the meridians, relieve pain, and invigorate blood circulation. Cinnamon twig contains volatile oils, phenols, organic acids, polysaccharides, glycosides, coumarins, and tannins, and has the effects of inducing sweating and relieving muscle tension, warming and unblocking the meridians, assisting yang qi, and calming and descending qi.

[0013] Red peony root: The dried root of Paeonia lactiflora or Paeonia veitchii, both belonging to the Ranunculaceae family. It tastes bitter and is slightly cold in nature, with a strong purgative effect. It has the functions of clearing heat and cooling blood, dispersing blood stasis and relieving pain, promoting blood circulation and reducing swelling. Clinically, it is often used for heat entering the blood level, traumatic injuries, carbuncles, and sores. Modern research shows that the active ingredients of red peony root can inhibit platelet aggregation, regulate endocrine function, and have various pharmacological effects such as anti-tumor, anti-inflammatory, antibacterial, antidepressant, improving microcirculation, and inhibiting the production of inflammatory factors.

[0014] Ephedra: The dried herbaceous stem of *Ephedra sinica*, *Ephedra intermedia*, or *Ephedra equisetifolia*, belonging to the Ephedraceae family. It is pungent, slightly bitter, and warm in nature, and is a primary herb for relieving exterior syndromes. It can clear the lungs and open the pores, regulate water metabolism, and reduce swelling. The *Shennong Bencao Jing* records that ephedra can "induce sweating, eliminate cold and heat, and break up masses and accumulations." Ephedra is pungent and dispersing, moving without lingering, dispelling wind, relieving pain, and allowing the three evils of wind, cold, and dampness residing in the joints to be dispersed. The main components of ephedra are alkaloids, which reduce inflammatory factors, lessen the degree of joint damage, promote blood circulation in the affected limb, relieve pain, and slow disease progression.

[0015] Anemarrhena asphodeloides: The dried rhizome of the plant Anemarrhena asphodeloides, belonging to the Liliaceae family. It tastes bitter and sweet, and is cold in nature. It has the effects of clearing heat and purging fire, nourishing yin and moistening dryness. When combined with Paeonia lactiflora, Anemarrhena asphodeloides can clear heat from the middle jiao, nourish yin, and counteract the warming and drying properties of Ephedra sinica. Modern research shows that the active ingredients in Anemarrhena asphodeloides have significant effects in antipyretics and anti-inflammation.

[0016] Glauber's salt: A crystalline form refined from the sulfate mineral Glauber's salt (of the Glauber's salt group). It has a bitter, salty, and cold nature. Glauber's salt has laxative, moisturizing, softening, dispersing, and lithospermic effects. Clinically, it is commonly reported to be used to treat erysipelas, gouty arthritis, gallstones, mastitis, and skin diseases. It can be absorbed through the skin, increasing local blood drug concentration to achieve anti-inflammatory, swelling-reducing, and pus-draining effects.

[0017] Gardenia: The dried, ripe fruit of the gardenia plant (family Rubiaceae). It is cold in nature and bitter in taste, and has the effects of clearing lung heat, stopping coughs caused by lung heat, cooling the blood, and detoxifying. It is used for boils and sores caused by fire toxins, and externally for sprains and contusions. It has anti-inflammatory, antioxidant, soothing, sedative, and sleep-improving effects, and treats sprains and contusions. Among its active ingredients, geniposide has a soft tissue protective effect, can promote the proliferation of ligament fibroblasts and the synthesis of collagen, and improve ligament damage.

[0018] Borneol: Natural borneol is a processed resin or crystalline extract from the trunk of the Dipterocarpus natans plant (family Dipterocarpaceae). Synthetic borneol is chemically synthesized from raw materials such as turpentine and camphor. It is bitter, slightly cold, and cooling in nature, possessing the functions of clearing heat and detoxifying, reducing swelling and relieving pain, and promoting tissue regeneration and wound healing. Modern research shows that borneol has anti-inflammatory, analgesic, and antibacterial properties, and can improve the bioavailability of other drugs. It can affect the distribution of drugs, prolong the duration of action, and thus improve the efficacy of drugs. As an adjuvant, it is often used in combination with Glauber's salt to enhance the bioavailability of Glauber's salt.

[0019] Traditional Chinese medicine (TCM) treats gout from the perspective of "heat-induced arthralgia," focusing on clearing heat and detoxifying to alleviate symptoms of redness, swelling, heat, and pain. However, this invention, through clinical observation, reveals that many gout patients are influenced by cold factors, such as exposure to cold environments, consumption of cold foods, and inadequate local warmth, which can trigger gout attacks. Coldness leads to stagnation, resulting in poor circulation in the meridians of the extremities, causing dampness and toxins to accumulate and transform into heat, forming a complex pattern of cold and heat-induced arthralgia. Based on these clinical observations, the topical TCM composition for treating acute gouty arthritis in this invention breaks through the limitations of traditional single-method approaches of clearing heat and detoxifying, achieving an organic combination of clearing heat and detoxifying to reduce swelling with promoting blood circulation, dispelling wind, and unblocking meridians. In this prescription, Gardenia and Glauber's salt are used as the principal herbs, leveraging their heat-clearing and swelling-reducing properties to quickly alleviate acute symptoms of redness, swelling, heat, and pain. Simultaneously, based on traditional Chinese medicine theory, Cinnamon twig, Ephedra, and Red peony root are innovatively added as assistant herbs. Cinnamon twig warms and unblocks the meridians, while Ephedra is pungent and dispersing, clearing the meridians and dispelling cold. Their synergistic effect helps to expel cold pathogens from the body. Combined with Red peony root to nourish blood, promote blood circulation, and dispel numbness, it clears the pathways for pathogens to escape. Anemarrhena rhizome is used as an adjuvant herb, enhancing the heat-clearing and numbness-dispelling effects while balancing the warming and drying properties of the assistant herbs. Finally, Borneol is used as the guiding herb, not only clearing heat and reducing swelling but also enhancing transdermal absorption, ensuring the medication reaches the lesion directly.

[0020] While existing drug treatments for acute gouty arthritis have some effectiveness, they can cause adverse reactions. Common traditional Chinese medicine powdered topical applications are inconvenient, slow-acting, difficult to store, and prone to bacterial infection. Currently known ointments with anti-swelling and analgesic functions often involve topical application of powdered traditional Chinese medicine, which is inconvenient to use, has a strong odor, limited efficacy, low drug loading capacity, poor transdermal absorption, short duration of effect, and drawbacks such as irritation, allergies, and premature aging.

[0021] To address the aforementioned shortcomings in existing technologies, this invention designs a treatment route for acute gouty arthritis based on drug dosage form and administration route, using a topical application method. The active ingredients of traditional Chinese medicine extracts are combined with a matrix to form a "pain-relieving and wind-dispelling" gel. In this design, the components of the traditional Chinese medicine extracts can interact to aggregate or self-assemble into aggregates, using the gel as a carrier medium for the active ingredients, thus increasing the content of the active ingredients.

[0022] Specifically, this invention involves first extracting the above-mentioned traditional Chinese medicine (TCM) raw materials through reflux, followed by repeated dialysis separation to obtain TCM nanoparticles. This allows for the effective extraction and concentration of the active components of the TCM. Further, carbomer, glycerin, sodium hyaluronate, 1,3-butanediol, propylene glycol, triethanolamine, etc., are added to form a gel. The resulting product not only effectively solves the problems of inconvenience, slow effect, low risk of infection, and uncertain function in existing physical therapy methods, avoiding a series of adverse reactions after drug administration, but also adheres tightly to the site of action for a longer period, avoiding the first-pass effect of oral administration. The gel has the characteristics of high drug concentration, low volatility, and long-lasting effect, thereby increasing the local drug concentration and prolonging the drug release or diffusion process.

[0023] This invention prepares a gel by separating the active ingredients of a compound extract into a nano-phase. Carbomer 940 is a very important rheology modifier. Neutralized carbomer is an excellent gel matrix with important uses such as thickening and suspension. It has good stability, short rheological properties, high viscosity, high clarity, low ionic resistance, and shear resistance, making it suitable for gels and creams. Sodium hyaluronate is a component of human skin and is one of the most widely distributed acidic mucosaccharides in the human body. It exists in the matrix of connective tissue and has good moisturizing and repairing effects, while also enhancing the efficacy of medicines. It has high viscosity in aqueous solution, with a 1% aqueous solution forming a gel, and can act as a thickener and stabilizer.

[0024] Preferably, the traditional Chinese medicine composition for acute gouty arthritis of the present invention comprises the following components by mass percentage: 10-20% traditional Chinese medicine nanophase material, 1-4% carbomer 940, 5-10% glycerin, 0.02-0.1% sodium hyaluronate, 1-4% 1,3-butanediol, 1-5% propylene glycol, 1-6% triethanolamine, and the balance being distilled water.

[0025] More preferably, the product comprises the following components by mass percentage: 15% of traditional Chinese medicine nano-phase material, 1.5% of carbomer 940, 10% of glycerin, 0.05% of sodium hyaluronate, 2.5% of 1,3-butanediol, 2.5% of propylene glycol, 3.0% of triethanolamine, and the balance being distilled water.

[0026] For the traditional Chinese medicine raw materials of the traditional Chinese medicine composition for acute gouty arthritis of the present invention, the traditional Chinese medicine nanophase material is preferably made from the following raw materials in parts by weight: 1-5 parts of cinnamon twig, 1-5 parts of red peony root, 1-3 parts of ephedra, 1-5 parts of anemarrhena rhizome, 3-12 parts of mirabilite, 2-6 parts of gardenia fruit, and 1-5 parts of borneol.

[0027] More preferably, the traditional Chinese medicine nanophase material is made from the following raw materials in parts by weight: 1 part cinnamon twig, 1-2 parts red peony root, 1 part ephedra, 1-2 parts anemarrhena rhizome, 5-10 parts mirabilite, 2-3 parts gardenia fruit, and 1 part borneol.

[0028] Specifically, the preparation method of the traditional Chinese medicine nanoparticles includes the following steps:

[0029] A. Take a dialysis bag with a relative molecular mass cutoff of 100-400, put it into distilled water containing 1-3 wt.% sodium bicarbonate and 0.5-2 mmol / L EDTA-Na2 at pH 8, boil for 5-15 minutes, cool, and store in 30-70% ethanol at 1-6℃ for later use.

[0030] B. Weigh out the following ingredients according to the specified proportions: cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite, and gardenia fruit. Place them in a round-bottom flask, add 5-15 times the volume of water, soak for 20-40 minutes, reflux for 10-30 minutes, filter while hot, add 5-15 times the volume of water to the residue, reflux for 10-30 minutes, filter while hot through a 100-300 mesh filter cloth, combine the filtrates, and concentrate under reduced pressure to 0.3-1.0 g / ml to obtain the total extract of the compound Chinese medicine.

[0031] C. At room temperature, centrifuge the total extract of the compound Chinese medicine from step B at 7000-10000 rpm for 20-40 min, collect the precipitate, and set aside for later use;

[0032] D. Take the dialysis bag from step A, add the supernatant from step C (centrifugation), place it in a beaker containing ultrapure water, and dialyze for 20-40 minutes. Remove the sample from the dialysis bag, centrifuge at 10000-13000 rpm for 20-40 minutes, aspirate the supernatant, and combine the trace precipitate with the precipitate from step C. Repeat the above dialysis and centrifugation steps 3-6 times, combine the precipitates, and set aside for later use.

[0033] E. Weigh borneol, add anhydrous ethanol to make a 5-15% borneol alcohol solution, add the precipitate combined in step D, stir well, and you will get the traditional Chinese medicine nano-phase material.

[0034] The topical Chinese medicine composition for treating acute gouty arthritis of the present invention can be formulated into a gel form, or further formulated into a gel, paste, ointment, spray or plaster for use.

[0035] In a second aspect, a method for preparing a traditional Chinese medicine composition for acute gouty arthritis according to the present invention is provided, comprising the following steps:

[0036] (1) Preparation of nano-phase materials of traditional Chinese medicine:

[0037] A. Take a dialysis bag with a relative molecular mass cutoff of 100-400, put it into distilled water containing 1-3 wt.% sodium bicarbonate and 0.5-2 mmol / L EDTA-Na2 at pH 8, boil for 5-15 minutes, cool, place in 30-70% ethanol, and store at 1-6℃ for later use.

[0038] B. Weigh out the following ingredients according to the specified proportions: cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite, and gardenia fruit. Place them in a round-bottom flask, add 5-15 times the volume of water, soak for 20-40 minutes, reflux for 10-30 minutes, filter while hot, add 5-15 times the volume of water to the residue, reflux for 10-30 minutes, filter while hot through a 100-300 mesh filter cloth, combine the filtrates, and concentrate under reduced pressure to 0.3-1.0 g / ml to obtain the total extract of the compound Chinese medicine.

[0039] C. At room temperature, centrifuge the total extract of the compound Chinese medicine from step B at 7000-10000 rpm for 20-40 min, collect the precipitate, and set aside for later use;

[0040] D. Take the dialysis bag from step A, add the supernatant from step C (centrifugation), place it in a beaker containing ultrapure water, and dialyze for 20-40 minutes. Remove the sample from the dialysis bag, centrifuge at 10000-13000 rpm for 20-40 minutes, aspirate the supernatant, and combine the trace precipitate with the precipitate from step C. Repeat the above dialysis and centrifugation steps 3-6 times, combine the precipitates, and set aside for later use.

[0041] E. Weigh borneol, add anhydrous ethanol to make a 5-15% borneol alcohol solution, add the precipitate combined in step D, stir well, and you will get the traditional Chinese medicine nano-phase material.

[0042] (2) Weigh out Carbomer 940 and sodium hyaluronate respectively, add distilled water, heat and stir to make them completely swollen, then add glycerin, traditional Chinese medicine nano-phase material, 1,3-butanediol and propylene glycol, and make up the remainder with distilled water;

[0043] (3) Add triethanolamine to the mixed solution in step (2) to adjust the pH to 4-7, stir slowly and evenly in the same direction until a clear, fine and uniform yellow transparent gel is formed, fill, sterilize and package to obtain the product.

[0044] Preferably, the preparation steps of traditional Chinese medicine nanoparticles include:

[0045] A. Take a dialysis bag with a relative molecular mass cutoff of 200, put it into distilled water containing 2 wt.% sodium bicarbonate and 1 mmol / L EDTA-Na2 at pH 8, boil for 10 min, cool, place in 50% ethanol, and store at 4℃ for later use.

[0046] B. Weigh out the following ingredients according to the proportions: cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite, and gardenia fruit. Place them in a round-bottom flask, add 12 times the volume of water and soak for 30 minutes. Reflux for 20 minutes and filter while hot. Add 10 times the volume of water to the residue and reflux for 20 minutes. Filter while hot through a 200-mesh filter cloth. Combine the filtrates and concentrate under reduced pressure to 0.5 g / ml to obtain the total extract of the compound Chinese medicine.

[0047] C. At room temperature, centrifuge the total extract of the compound Chinese medicine from step B at 10,000 rpm for 30 min, collect the precipitate, and set aside for later use;

[0048] D. Take the dialysis bag from step A, add the supernatant from step C after centrifugation, place it in a beaker containing ultrapure water and dialyze for 30 minutes. Take out the sample from the dialysis bag, centrifuge at 13000 rpm for 30 minutes, aspirate the supernatant, and combine the trace precipitate with the precipitate from step C. Repeat the above dialysis and centrifugation steps 3-6 times, combine the precipitates, and set aside for later use.

[0049] E. Weigh borneol, add anhydrous ethanol to make a 5-12% borneol alcohol solution, add the precipitate combined in step D, stir well, and you will get the traditional Chinese medicine nanophase material.

[0050] In a third aspect, the use of the traditional Chinese medicine composition of the present invention in the preparation of a medicament for treating acute gouty arthritis is provided, the medicament being administered topically.

[0051] Furthermore, the dosage form of the drug is a gel, paste, ointment, spray, or patch.

[0052] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0053] (1) This invention realizes that the administration route for treating acute gouty arthritis is set as topical application, which can reduce the probability and dosage of oral analgesics, prevent side effects, solve the shortcomings of small drug loading and strong odor of plasters, reduce the loss of active ingredients, enhance the ability of drugs to penetrate the treatment site, and prolong the drug release process.

[0054] (2) In terms of Chinese medicine formulation, this invention continues the traditional advantages of treating gout and heat-induced arthralgia by using gardenia and Glauber's salt to clear heat, activate blood circulation, reduce swelling and relieve pain, and quickly alleviate the symptoms of red, swollen and hot joints. On the other hand, in response to the internal pathogenesis of gout induced by cold evil and the complex combination of cold and heat, it innovatively incorporates warming and activating medicinal materials, namely cinnamon twig, which can activate blood circulation and regulate menstruation, and warm and disperse cold evil; ephedra, which is pungent and dispersing, can dispel cold and dampness on the body surface. The two are combined with red peony root, which activates blood circulation and regulates menstruation, and anemarrhena rhizome, which clears heat and stagnation, to form a treatment system that takes into account both the exterior and interior, uses both cold and warm, and regulates yin and yang. In this combination, cinnamon twig and red peony root can both dredge the meridians, dispel pain, and promote blood circulation by leveraging the warming and unblocking power of cinnamon twig, and avoid dryness by relying on the heat-clearing and blood-activating properties of red peony root while nourishing and activating blood. Ephedra is pungent and dispersing, activates blood circulation and removes pain, and can dispel wind, relieve pain, and expel the three evils of wind, cold and dampness that have lingered in the joints from the inside to the outside. When combined with red peony root, it can warm the meridians, dispel cold and relieve pain, while avoiding damage to yin fluid by leveraging the blood-nourishing effect of red peony root, and will not trap evil. The synergy between ephedra and cinnamon twig further enhances the effects of warming the meridians, unblocking the meridians, dispelling cold and relieving pain. In addition, the effects of borneol in clearing heat, reducing swelling and promoting transdermal absorption make this Chinese medicine composition particularly suitable for acute gouty arthritis caused by a mixture of cold and heat and the accumulation of wind, cold and dampness in the body over a long period of time. It is more in line with the pathogenesis, has a deeper effect, and effectively makes up for the shortcomings of traditional single heat-clearing treatment. It can better unblock the meridians, expel evil to the outside, and improve the range of motion and prognosis of gouty joints.

[0055] (3) In terms of dosage form, this invention targets specific traditional Chinese medicine nanoparticles and selects carbomer, glycerin, sodium hyaluronate, 1,3-butanediol, propylene glycol, triethanolamine and distilled water as the carrier medium composition, which ensures the relief and release of the active ingredients, increases the penetration to the painful site, and promotes skin absorption. It is an effective way to improve the administration route for the treatment of acute gouty arthritis. Adding the active ingredients in the form of nanoparticles has significant advantages in terms of drug loading, promoting drug absorption and improving drug bioavailability. Attached Figure Description

[0056] Figure 1 This is a schematic diagram of the preparation process of the nano-phase in the preparation method of the topical Chinese medicine composition for treating acute gouty arthritis of the present invention.

[0057] Figure 2 This is a diagram illustrating the comparison within the joint symptom scoring group.

[0058] Figure 3 This is a diagram illustrating the comparison between joint symptom score groups.

[0059] Figure 4 This is a diagram illustrating the comparison of VAS pain scores within a joint group.

[0060] Figure 5 This is a schematic diagram showing the differences between VAS pain score groups for joints.

[0061] Figure 6This is a schematic diagram showing the comparison of joint swelling scores within each group.

[0062] Figure 7 This is a schematic diagram comparing the joint swelling scores between groups.

[0063] Figure 8 This is a schematic diagram showing the comparison within the joint mobility limitation score group.

[0064] Figure 9 This is a schematic diagram comparing the scores of groups with limited joint mobility.

[0065] Figure 10 This is a diagram showing the patient's condition before medication.

[0066] Figure 11 The patient's condition after 2 days of medication.

[0067] Figure 12 The image shows the patient's condition before medication.

[0068] Figure 13 The patient's condition after 3 days of medication is shown in the image.

[0069] Figure 14 The image shows the patient's condition before medication.

[0070] Figure 15 The patient's condition after 3 days of medication is shown in the image.

[0071] Figure 16 A representative photograph of MSU-induced ankle swelling in rats captured 12 hours after injection.

[0072] Figure 17 The hindfoot use scores of AGA rats at different time points after modeling were compared among the groups.

[0073] Figure 18 Comparison of ankle skin temperature at different time points after modeling in each group of AGA rats.

[0074] Figure 19 This is the VAS rating scale. Detailed Implementation

[0075] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0076] Example 1:

[0077] Composition of Chinese medicinal materials: 1.5 kg of cinnamon twig, 2 kg of red peony root, 1.5 kg of ephedra, 2 kg of anemarrhena rhizome, 8 kg of mirabilite, 2.5 kg of gardenia fruit, and 1.5 kg of borneol.

[0078] The raw material composition of the traditional Chinese medicine preparation is as follows: 1 kg Carbomer 940, 5 kg Glycerin, 0.05 kg Sodium Hyaluronate, 15 kg Traditional Chinese Medicine Nanoparticles, 2 kg 1,3-Butanediol, 3 kg Propylene Glycol, 2.5 kg Triethanolamine, and the balance is distilled water, totaling 100 kg.

[0079] like Figure 1 As shown, the preparation method is as follows: (1) Preparation of traditional Chinese medicine nanoparticles: Take a dialysis bag with a relative molecular mass cutoff of 150, put it into distilled water containing 1.5wt.% sodium bicarbonate and 1mmol / L EDTA-Na2 at pH 8 and boil for 10min. Cool it and place it in 50% ethanol. Store it at 3℃ for later use. Weigh out cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite and gardenia according to the proportion. Place them in a round bottom flask, add 10 times the volume of water and soak for 20min. Reflux extract for 15min. Filter while hot. Add 10 times the volume of water to the residue and reflux extract for 25min. Filter while hot through a 150-mesh filter cloth. Combine the filtrates and concentrate under reduced pressure to 0.5g / ml to obtain the total extract of compound traditional Chinese medicine. At room temperature, centrifuge the total extract of compound traditional Chinese medicine at 10000rpm for 30min and collect the precipitate for later use. Take a dialysis bag and add the centrifuged mixture. The supernatant was placed in a beaker containing ultrapure water and dialyzed for 25 minutes. The sample in the dialysis bag was taken out and centrifuged at 13000 rpm for 25 minutes. The supernatant was aspirated and the trace precipitate was combined with the previous precipitate. The above dialysis and centrifugation steps were repeated 3 times and the precipitates were combined. Borneol was weighed and anhydrous ethanol was added to make a 10% borneol alcohol solution. The combined precipitate was added and stirred evenly to obtain the Chinese medicine nanophase material. (2) Carbomer 940 and sodium hyaluronate were weighed separately, added to distilled water, heated and stirred to make them completely swollen, and then glycerol, Chinese medicine nanophase material, 1,3-butanediol and propylene glycol were added. The remainder was made up with distilled water. (3) Triethanolamine was added to the mixed solution in step (2) to adjust the pH to 5. The mixture was slowly and evenly stirred in the same direction until a clear, delicate and uniform yellow transparent gel was formed. The gel was filled, sterilized and packaged to obtain the product.

[0080] Example 2:

[0081] Composition of Chinese medicinal materials: 1 kg of cinnamon twig, 1.5 kg of red peony root, 1 kg of ephedra, 2 kg of anemarrhena rhizome, 10 kg of mirabilite, 3 kg of gardenia fruit, and 1 kg of borneol.

[0082] The raw material composition of the traditional Chinese medicine preparation is as follows: 1.5 kg Carbomer 940, 10 kg Glycerin, 0.05 kg Sodium Hyaluronate, 15 kg Traditional Chinese Medicine Nanoparticle 2, 2.5 kg 1,3-Butanediol, 2.5 kg Propylene Glycol, 5 kg Triethanolamine, and the balance is distilled water, totaling 100 kg.

[0083] like Figure 1 As shown, the preparation method is as follows: (1) Preparation of traditional Chinese medicine nanoparticles: Take a dialysis bag with a molecular weight cutoff of 200, put it into distilled water containing 2wt.% sodium bicarbonate and 1mmol / L EDTA-Na2 at pH 8 and boil for 10min. Cool it and place it in 50% ethanol. Store it at 4℃ for later use. Weigh out cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite and gardenia according to the proportion, put them in a round bottom flask, add 12 times the volume of water and soak for 30min. Reflux extract for 20min. Filter while hot. Add 10 times the volume of water to the residue and reflux extract for 20min. Filter while hot through a 200-mesh filter cloth. Combine the filtrates and concentrate under reduced pressure to 0.5g / ml to obtain the total extract of compound traditional Chinese medicine. Centrifuge the total extract of compound traditional Chinese medicine at 9000rpm for 30min at room temperature and collect the precipitate for later use. Take a dialysis bag and add the supernatant after centrifugation. The liquid was placed in a beaker containing ultrapure water and dialyzed for 30 min. The sample in the dialysis bag was taken out and centrifuged at 12000 rpm for 40 min. The supernatant was taken out and the trace precipitate was combined with the previous precipitate. The above dialysis and centrifugation steps were repeated 5 times and the precipitates were combined. Borneol was weighed and anhydrous ethanol was added to make a 10% borneol solution. The combined precipitate was added and stirred evenly to obtain the Chinese medicine nanophase material. (2) Carbomer 940 and sodium hyaluronate were weighed separately, added to distilled water, heated and stirred to make it completely swollen, and then glycerol, Chinese medicine nanophase material, 1,3-butanediol and propylene glycol were added. The remainder was made up with distilled water. (3) Triethanolamine was added to the mixed solution in step (2) to adjust the pH to 7. The mixture was slowly and evenly stirred in the same direction until a crystal clear, delicate and uniform yellow transparent gel was formed. The gel was filled, sterilized and packaged to obtain the product.

[0084] Example 3:

[0085] Composition of Chinese medicinal materials: 1 kg of cinnamon twig, 2 kg of red peony root, 1 kg of ephedra, 1.5 kg of anemarrhena rhizome, 5 kg of mirabilite, 2.5 kg of gardenia fruit, and 1 kg of borneol.

[0086] The raw material composition of the traditional Chinese medicine preparation is as follows: 2 kg of carbomer 940, 8 kg of glycerin, 0.05 kg of sodium hyaluronate, 18 kg of traditional Chinese medicine nano-phase material, 3 kg of 1,3-butanediol, 4 kg of propylene glycol, 3 kg of triethanolamine, and the balance is distilled water, totaling 100 kg.

[0087] like Figure 1As shown, the preparation method is as follows: (1) Preparation of traditional Chinese medicine nanoparticles: Take a dialysis bag with a molecular weight cutoff of 200, put it into distilled water containing 2.5wt.% sodium bicarbonate and 0.9mmol / L EDTA-Na2 at pH 8 and boil for 12min. Cool it and place it in 45% ethanol. Store it at 5℃ for later use. Weigh out cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite and gardenia according to the proportion, put them in a round bottom flask, add 12 times the volume of water and soak for 35min. Reflux extract for 25min. Filter while hot. Add 13 times the volume of water to the residue and reflux extract for 25min. Filter while hot through a 200-mesh filter cloth. Combine the filtrates and concentrate under reduced pressure to 0.7g / ml to obtain the total extract of compound traditional Chinese medicine. At room temperature, centrifuge the total extract of compound traditional Chinese medicine at 7000rpm for 35min and collect the precipitate for later use. Take a dialysis bag and add the centrifuged mixture. The supernatant was placed in a beaker containing ultrapure water and dialyzed for 30 min. The sample in the dialysis bag was taken out and centrifuged at 10,000 rpm for 35 min. The supernatant was aspirated and the trace precipitate was combined with the previous precipitate. The above dialysis and centrifugation steps were repeated 6 times and the precipitates were combined. Borneol was weighed and anhydrous ethanol was added to make a 13% borneol alcohol solution. The combined precipitate was added and stirred evenly to obtain the Chinese medicine nanophase material. (2) Carbomer 940 and sodium hyaluronate were weighed separately, added to distilled water, heated and stirred to make them completely swollen, and then glycerol, Chinese medicine nanophase material, 1,3-butanediol and propylene glycol were added. The remainder was made up with distilled water. (3) Triethanolamine was added to the mixed solution in step (2) to adjust the pH to 6. The mixture was slowly and evenly stirred in the same direction until a clear, delicate and uniform yellow transparent gel was formed. The gel was filled, sterilized and packaged to obtain the product.

[0088] Example 4:

[0089] Composition of Chinese medicinal materials: 1.0 kg of cinnamon twig, 4 kg of red peony root, 3 kg of ephedra, 1 kg of anemarrhena rhizome, 10 kg of mirabilite, 4 kg of gardenia fruit, and 3 kg of borneol.

[0090] The raw material composition of the traditional Chinese medicine preparation is as follows: 2.5 kg of carbomer 940, 8 kg of glycerin, 0.1 kg of sodium hyaluronate, 10 kg of traditional Chinese medicine nano-phase material 4, 2.5 kg of 1,3-butanediol, 3.5 kg of propylene glycol, 3 kg of triethanolamine, and the balance is distilled water, totaling 100 kg.

[0091] like Figure 1As shown, the preparation method is as follows: (1) Preparation of traditional Chinese medicine nanoparticles: Take a dialysis bag with a molecular weight cutoff of 400, put it into distilled water containing 1.5wt.% sodium bicarbonate and 1.5mmol / L EDTA-Na2 at pH 8 and boil for 8 minutes. Cool it and place it in 55% ethanol. Store it at 3℃ for later use. Weigh out cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite and gardenia according to the proportion, put them in a round bottom flask, add 10 times the volume of water and soak for 25 minutes. Reflux extract for 30 minutes. Filter while hot. Add 10 times the volume of water to the residue and reflux extract for 20 minutes. Filter while hot through a 100-mesh filter cloth. Combine the filtrates and concentrate under reduced pressure to 0.8g / ml to obtain the total extract of compound traditional Chinese medicine. At room temperature, centrifuge the total extract of compound traditional Chinese medicine at 10000rpm for 30 minutes and collect the precipitate for later use. Take a dialysis bag and add the centrifuged product. The supernatant was placed in a beaker containing ultrapure water and dialyzed for 30 min. The sample in the dialysis bag was taken out and centrifuged at 12000 rpm for 25 min. The supernatant was aspirated and the trace precipitate was combined with the previous precipitate. The above dialysis and centrifugation steps were repeated 4 times and the precipitates were combined. Borneol was weighed and anhydrous ethanol was added to make a 12% borneol alcohol solution. The combined precipitate was added and stirred evenly to obtain the Chinese medicine nanophase material. (2) Carbomer 940 and sodium hyaluronate were weighed separately, added to distilled water, heated and stirred to make them completely swollen, and then glycerol, Chinese medicine nanophase material, 1,3-butanediol and propylene glycol were added. The remainder was made up with distilled water. (3) Triethanolamine was added to the mixed solution in step (2) to adjust the pH to 4. The mixture was slowly and evenly stirred in the same direction until a crystal clear, delicate and uniform yellow transparent gel was formed. The gel was filled, sterilized and packaged to obtain the product.

[0092] Example 5:

[0093] The ingredients of the Chinese medicinal materials are: 6 kg of cinnamon twig, 2 kg of red peony root, 4 kg of ephedra, 3 kg of anemarrhena rhizome, 13 kg of mirabilite, 7 kg of gardenia fruit, and 7 kg of borneol.

[0094] The raw material composition of the traditional Chinese medicine preparation is as follows: 2.0 kg carbomer 940, 6 kg glycerin, 0.15 kg sodium hyaluronate, 12 kg traditional Chinese medicine nano-phase material 5, 2.8 kg 1,3-butanediol, 3.6 kg propylene glycol, 3.1 kg triethanolamine, and the balance is distilled water, totaling 100 kg.

[0095] like Figure 1As shown, the preparation method is as follows: (1) Preparation of traditional Chinese medicine nanoparticles: Take a dialysis bag with a molecular weight cutoff of 100, put it into distilled water containing 3wt.% sodium bicarbonate and 2mmol / L EDTA-Na2 at pH 8 and boil for 5 minutes. Cool it and place it in 35% ethanol. Store it at 1℃ for later use. Weigh out cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite and gardenia according to the proportion, put them in a round bottom flask, add 6 times the volume of water and soak for 25 minutes. Reflux extract for 20 minutes and filter while hot. Add 10 times the volume of water to the residue and reflux extract for 25 minutes. Filter while hot through a 200-mesh filter cloth. Combine the filtrates and concentrate under reduced pressure to 1.0g / ml to obtain the total extract of compound traditional Chinese medicine. At room temperature, centrifuge the total extract of compound traditional Chinese medicine at 8000rpm for 35 minutes and collect the precipitate for later use. Take a dialysis bag and add the supernatant after centrifugation. , place in a beaker containing ultrapure water and dialyze for 25 min, take out the sample from the dialysis bag, centrifuge at 11000 rpm for 25 min, aspirate the supernatant, combine the trace precipitate with the previous precipitate, repeat the above dialysis and centrifugation steps 6 times, and combine the precipitates obtained; weigh borneol, add anhydrous ethanol to make a 9% borneol alcohol solution, add the combined precipitate, stir well, and obtain the Chinese medicine nano-phase material; (2) weigh carbomer 940 and sodium hyaluronate respectively, add distilled water, heat and stir to make it completely swollen, then add glycerol, Chinese medicine nano-phase material, 1,3-butanediol and propylene glycol, and make up the remainder with distilled water; (3) add triethanolamine to the mixed solution in step (2) to adjust the pH to 6, stir slowly and evenly in the same direction until a crystal clear, delicate and uniform yellow transparent gel is formed, fill, sterilize and package, and obtain.

[0096] Experimental Example 1:

[0097] The intervention effect of the gel of Example 1 of this invention on acute gouty arthritis was studied by administering the gel to a rat model of acute gouty arthritis.

[0098] 1. Experimental Design

[0099] 1.1 Basic feeding.

[0100] Forty-two SPF-grade male SD rats (180-220g) were selected and acclimatized for 7 days. The environment was 22±2℃ and 50%±10% with free access to standard rat food and pure water. The bedding was changed every 3 days, and the activity and fecal condition were observed.

[0101] 1.2 Animal modeling methods.

[0102] Thirty-six rats were randomly selected to prepare an acute gouty arthritis model. The method was as follows: (1) From day 1 to day 7, the rats were fed a high-fat, high-purine diet and their tails were immersed in cold water (3 cm deep) at 0-4°C for 10 minutes each day to construct a mixed cold and heat syndrome model; (2) On day 7, after intraperitoneal injection of tribromoethanol for anesthesia, 0.2 mL of sodium urate solution (25 mg / ml) was injected into the right ankle joint to induce acute inflammation.

[0103] 1.3 Administration method.

[0104] Six normally fed rats were used as the control group. Thirty-six rats after modeling were randomly divided into six groups of six each. The following composition was administered to the rats on days 8-14 at 9:00 a.m. each day.

[0105] (1) Control group: standard diet + 1 mL / 100 g of normal saline by gavage + 0.4 g of normal saline applied to joints each time;

[0106] (2) Model group: standard diet + 1 mL / 100 g of normal saline by gavage + 0.4 g of normal saline applied to joints each time;

[0107] (3) The present invention group (pain-relieving and wind-dispelling gel group): After degreasing the skin of the joints, apply 0.4g of the gel of Example 1 and wrap with plastic wrap for 30 minutes;

[0108] (4) Comparative Group 1 (Gardenia, Glauber's Salt, and Borneol Group): Gardenia, Glauber's Salt, and Borneol were prepared into a gel at a mass ratio of 1:3:2. The preparation method and administration method were the same as those of the present invention group.

[0109] (5) Control group 2 (diclofenac sodium group): After degreasing the skin of the joints, apply 0.4g of diclofenac sodium cream and wrap with plastic wrap for 30 minutes;

[0110] (6) Control group 3 (Guizhi Shaoyao Zhimu Decoction Gavage Group): Guizhi, Chishao and Zhimu were decocted in water at a mass ratio of 4:4:5 and administered by gavage at a dose of 12g / kg / d.

[0111] (7) Control group 4 (Guizhi Shaoyao Zhimu Decoction for external use): Guizhi, Chishao and Zhimu were prepared into an ointment in a mass ratio of 1:1:2. After degreasing the skin of the joints, 0.4g of the ointment was applied and wrapped with plastic wrap for 30 minutes.

[0112] 1.4 Detection Indicators

[0113] (1) Behavioral studies: hindfoot use score during walking (0-4 points, record lifting behavior for 5 minutes);

[0114] Table 1 Walking Heel Use Rating

[0115]

[0116] (2) Physical signs: The diameter of the ankle joint of each group of rats was measured with vernier calipers before modeling and at 4h, 8h, 12h, 24h and 48h after modeling. The ankle joint swelling was calculated as follows: ankle joint swelling = (ankle joint diameter after modeling - ankle joint diameter before modeling) / ankle joint diameter before modeling. The local skin temperature of the ankle joint of each group of rats was measured with an infrared thermometer. The entire experimental process was performed by the same person (to ensure the accuracy of the measurement as much as possible). Each group was measured 3 times, and the average value was taken as the result.

[0117] (3) Serum indicators: uric acid (SUA), C-reactive protein (CRP) and inflammatory factors (IL-1β, TNF-α, IL-6).

[0118] 2. Experimental Results

[0119] 2.1 Comparison of joint swelling in AGA rats at different time points in each group.

[0120] In the control group, rats showed mild ankle swelling after injection of saline. Compared with the control group, the swelling in the model group was significantly increased at 4, 12, 24, 48, and 72 hours after modeling (P < 0.01), peaking at 12 hours, indicating successful modeling. Figure 16 .

[0121] Table 2 Comparison of ankle joint swelling in AGA rats at different time points in each group ( ±s, n=6)

[0122] Note: Compared with the control group, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01.

[0123]

[0124] The results in Table 2 show that, 72 hours after modeling, the joint swelling was ranked from highest to lowest as follows: Model group > Control group 2 > Control group 3 > Control group 1 > Control group 4 > Invention group > Control group. This indicates that the drugs that can effectively relieve joint swelling are ranked as follows: Invention group > Control group 4 > Control group 1 > Control group 3 > Control group 2.

[0125] 2.2 Comparison of hindfoot use scores at different time points in different groups of AGA rats.

[0126] The control group rats had normal gait. Compared with the control group, the model group rats showed increased hindfoot use scores at 4, 12, 24, 48, and 72 hours after modeling (P < 0.05). At 72 hours after modeling, the hindfoot use scores, ranked from highest to lowest, were: Model Group > Control Group 2 > Control Group 3 > Control Group 1 > Control Group 4 > Invention Group = Control Group. This indicates that in terms of reducing hindfoot use scores and improving joint function, the drug's effectiveness, ranked from best to worst, was: Invention Group > Control Group 4 > Control Group 1 > Control Group 3 > Control Group 2. See details... Figure 17 .

[0127] 2.3 Comparison of ankle skin temperature at different time points in different groups of AGA rats.

[0128] The skin temperature of rats in the control group was normal, fluctuating around 36℃. Compared with the control group, the ankle skin temperature of rats in the model group increased at 4, 12, 24, 48, and 72 hours after modeling (P < 0.001). At 72 hours after modeling, the ankle skin temperature was ranked from highest to lowest as follows: Model group > Control group 2 > Control group 3 > Control group 1 > Control group 4 > This invention group > Control group. This indicates that the order of drugs for lowering ankle skin temperature is: This invention group > Control group 4 > Control group 1 > Control group 3 > Control group 2. See details... Figure 18 .

[0129] 2.4 Comparison of serum ALT, AST, BUN, and CREA levels in different groups of AGA rats.

[0130] There were no statistically significant differences in serum ALT, AST, BUN, and CREA levels among the AGA rat groups after treatment (P > 0.05), as shown in Table 3.

[0131] Table 3 Comparison of serum ALT, AST, BUN, and CREA levels in AGA rats from different groups ( ±s, n=6)

[0132]

[0133] 2.5 Comparison of serum CRP and SUA levels in different groups of AGA rats.

[0134] Compared with the control group, the serum SUA and CRP levels of rats in the model group were significantly increased (P<0.01); compared with the model group, the CRP levels of the present invention group, control group 4, control group 3, and control group 1 were significantly decreased (P<0.05); the SUA levels of the present invention group and control group 4 were significantly decreased (P<0.05), as shown in Table 4.

[0135] Table 4 Comparison of serum CRP and SUA levels in AGA rats of different groups ±s, n=6)

[0136]

[0137] Note: Compared with the control group, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01.

[0138] 2.6 Comparison of serum IL-1β, IL-6 and TNF-α levels in different groups of AGA rats.

[0139] Compared with the control group, the serum levels of IL-1β, IL-6, and TNF-α in the model group rats were significantly increased (P<0.01); compared with the model group, the IL-1β levels in the present invention group and control group 4 were significantly decreased (P<0.05); the IL-6 levels in the present invention group, control group 4, control group 3, and control group 1 were significantly decreased (P<0.05); the TNF-α levels in the present invention group, control group 4, and control group 1 were significantly decreased (P<0.05), as shown in Table 5.

[0140] Table 5 Comparison of serum IL-1β, IL-6, and TNF-α levels in different AGA groups ( ±s, n=6)

[0141]

[0142] Note: Compared with the control group, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01.

[0143] 3. Results Analysis

[0144] This study established a rat model of acute gouty arthritis (AGA) and compared the effects of different drug administration regimens on joint symptoms, serum biochemical indicators, and inflammatory factors. The results are summarized below:

[0145] (1) Improvement effect on local joint symptoms.

[0146] Joint swelling: The joint swelling of rats in the model group was significantly higher than that in the control group 4-72 hours after modeling (P<0.01), and reached its peak at 12 hours, confirming successful modeling. Among all drug-treated groups, the group of the present invention showed the best effect in reducing joint swelling, with the lowest swelling at 72 hours (0.03±0.01), which was superior to other drug-treated groups, suggesting that the group of the present invention has a more significant effect in reducing joint swelling.

[0147] Foot use score after walking: The foot use score of rats in the model group was increased due to joint pain, while the score of the present invention group at 72h was the same as that of the control group and significantly lower than that of other drug administration groups, indicating that it has the best effect in improving joint function and restoring normal gait, and the control group was the second best.

[0148] Ankle skin temperature: The ankle skin temperature in the model group was significantly increased. The skin temperature recovery in the present invention group was the best at 72 hours, which was better than other drug administration groups, indicating that it has a significant advantage in relieving fever symptoms caused by local inflammation of the joint.

[0149] (2) Effects on serum biochemical indicators.

[0150] Liver and kidney function indicators (ALT, AST, BUN, CREA): There were no statistically significant differences in serum ALT, AST (liver function) and BUN, CREA (kidney function) levels among the rat groups after treatment (P>0.05), indicating that none of the administration regimens had a significant adverse effect on the liver and kidney function of rats and the safety profile was good.

[0151] Uric acid and inflammation-related markers (SUA, CRP): Serum uric acid (SUA) and C-reactive protein (CRP) levels in the model group were significantly higher than those in the control group (P < 0.01). In this invention group, both SUA and CRP levels were significantly reduced (P < 0.05 or P < 0.01), and the improvement in CRP was superior to that in control group 3 and control group 2, suggesting that it has outstanding effects in reducing uric acid and inhibiting systemic inflammatory response.

[0152] Regulation of inflammatory factors: Serum levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α were significantly elevated in the model group (P < 0.01). The inhibitory effect of the present invention group and control group 4 on IL-1β was the most significant (P < 0.05 or P < 0.01); the present invention group showed the best effect in reducing IL-6 (P < 0.01); the present invention group, control group 4, and control group 1 all showed significant inhibitory effects on TNF-α (P < 0.05). In summary, the present invention group has a better overall effect in downregulating multiple pro-inflammatory factors and reducing inflammatory damage.

[0153] (3) Overall conclusion.

[0154] In terms of improving joint swelling, function, and inflammatory markers, the drug efficacy, from best to worst, was: Invention Group > Control Group 4 > Control Group 1 > Control Group 3 > Control Group 2. All dosing regimens did not affect liver and kidney function in rats, indicating reliable safety. The Invention Group may reduce uric acid levels by inhibiting the release of pro-inflammatory factors such as IL-1β, IL-6, and TNF-α, thereby alleviating local joint swelling, pain, and fever, while rapidly restoring joint function. This is the optimal intervention regimen in this experiment.

[0155] Experimental Example 2:

[0156] This section investigates a randomized controlled clinical trial of a traditional Chinese medicine composition for the treatment of acute gouty arthritis according to the present invention.

[0157] 1. Treatment plan

[0158] 1.1 Basic treatment: (1) Conduct disease knowledge education and emphasize regular diet and regular daily routine; (2) During the treatment period, strict dietary management should be implemented, limiting the intake of high-purine foods, controlling weight, and limiting smoking and alcohol; (3) Choose shoes with good warmth and loose fit for the feet; (4) It is recommended to rest in bed, elevate the affected limbs, and carry out moderate joint function training 72 hours after the swelling has completely subsided; (5) Ensure sufficient water intake every day, and it is recommended to choose alkaline drinks such as soda water to promote the metabolism of uric acid in the body.

[0159] 1.2 Group Treatment

[0160] Group A: (1) Select the site of pain onset as the application site, clean the local skin, apply the product of this invention (Example 1) to the painful area for 2 hours, then remove and clean the skin. Apply once a day. (2) Take oral Western medicine (diclofenac sodium sustained-release capsule 50mg / capsule), 1 capsule / time, once a day. (3) The treatment course is 5 days.

[0161] Group B: (1) Select the site of pain onset as the application site, clean the local skin, grind gardenia, borneol and Glauber's salt into powder, mix with a small amount of water to form a paste, apply to the painful area, cover with gauze, if it falls off, fix with medical tape, leave for 2 hours, then remove and clean the skin. Apply once a day. (2) Take oral Western medicine (diclofenac sodium sustained-release capsule 50mg / capsule), 1 capsule / time, once a day. (3) Treatment course is 5 days.

[0162] Group C: (1) Oral administration of Western medicine only (diclofenac sodium sustained-release capsule 50mg / capsule), 1 capsule / time, once a day. (2) Treatment course of 5 days.

[0163] 2. Data Collection

[0164] 2.1 Safety assessment: The subjects were monitored for drug safety throughout the course of treatment, and abnormal symptoms were treated according to the pre-set intervention procedure. Subjects who withdrew or were lost to follow-up were classified, statistically analyzed and causally analyzed.

[0165] 2.2 Joint Symptom Score

[0166] (1) Pain level.

[0167] The Visual Analogue Scale (VAS) was used as a standardized tool to quantify the pain intensity during the acute phase of gouty arthritis. This scale uses a linear scale design, with a scoring range of 0 to 10, where 0 corresponds to "no discomfort" and 10 represents "unbearable pain." In practice, patients were asked to mark the location of their pain sensation on the marked line, with the starting point designated as a painless state and the ending point defined as an extreme pain state. See details... Figure 19 .

[0168] (2) Joint tenderness score.

[0169] 0 points: No tenderness;

[0170] 0-2 points: Mild tenderness (normal range of motion intact, requires pressure stimulation to elicit);

[0171] 2-4 points: Moderate tenderness (accompanied by protective posture and reduced passive range of motion of the joint);

[0172] 4-6 points: Severe tenderness (evoking defensive withdrawal movements, with a significant reduction in passive range of motion >50%).

[0173] (3) Joint swelling score.

[0174] 0 points: No swelling;

[0175] 0-2 points: Mild swelling (skin lines are partially preserved, and bony anatomical landmarks are identifiable);

[0176] 2-4 points: Swelling (loss of skin texture, blurred but palpable bony landmarks);

[0177] 4-6 points: Severe swelling (significantly increased skin tension with translucency, complete obscuring of bony structures);

[0178] (4) Joint movement restriction score.

[0179] 0 points: Unrestricted;

[0180] 0-2 points: Slight limitations (minor interference with daily activities, limited instrumental activities)

[0181] 2-4 points: Limited (can only complete basic self-care actions, requires assistance to complete transfer actions)

[0182] 4-6 points: Severely limited (completely dependent on assistive devices, unable to switch between sitting and standing positions)

[0183] 3. Comparison of general patient conditions and safety assessment

[0184] This study included 90 patients, and general information such as gender and age were analyzed in the experimental and control groups. The mean age of group A was (45.10±12.72) years, group B was (42.43±11.56) years, and group C was (39.16±12.64) years (see Table 6). No drug-related adverse events were observed in any participant during the trial period.

[0185] Table 6 Comparison of General Patient Information

[0186]

[0187] 4. Comparison of joint symptom scores before and after treatment in the three groups

[0188] Before treatment, there were no significant differences in joint symptom scores and TCM syndrome scores among the three groups. After treatment, both joint symptom scores and TCM syndrome scores in all three groups were significantly lower than before treatment (P<0.001). The decrease in joint symptom scores between group A and group B was statistically significant (P<0.05); the decrease in joint symptom scores between group B and group C was statistically significant (P<0.05); and the joint symptom scores in groups A and C were significantly lower than those in the control group (P<0.001). See Table 7. Figure 2 , Figure 3 .

[0189] Table 7 Comparison of joint symptom scores before and after treatment (points, ±s)

[0190]

[0191] Note: * P<0.05, ** P<0.01, *** P<0.001, the difference is statistically significant.

[0192] 5. Comparison of symptom scores before and after treatment

[0193] Before treatment, there were no significant differences in VAS pain scores, joint swelling scores, and joint mobility limitation scores among the three groups. After treatment, VAS pain scores, joint swelling scores, and joint mobility limitation scores in all three groups were significantly lower than before treatment (P<0.001), and the joint mobility limitation score in group A was significantly lower than that in groups B and C (P<0.05). There were no statistically significant differences in VAS pain scores and joint swelling scores between groups A and B or C after treatment. (See Table 8-10) Figures 4 to 9 .

[0194] Table 8 Comparison of VAS pain scores before and after treatment (points, ±s)

[0195]

[0196] Note: * P<0.05, ** P<0.01, *** P<0.001, the difference is statistically significant.

[0197] Table 9 Comparison of joint swelling scores before and after treatment (points, ±s)

[0198]

[0199] Note: * P<0.05, ** P<0.01, *** P<0.001, the difference is statistically significant.

[0200] Table 10 Comparison of joint range of motion limitation scores before and after treatment (points, ±s)

[0201]

[0202] Note: * P<0.05, ** P<0.01, *** P<0.001, the difference is statistically significant.

[0203] 6. Results Analysis

[0204] Comparison of the three groups of patients before and after treatment was conducted using paired-samples t-tests, with P < 0.05 considered statistically significant. Statistical analysis showed that P(A) < 0.001; P(B) < 0.001; P(C) < 0.001, all indicating significant differences. This demonstrates that the combination of oral Western medicine and the external application of "heat-clearing and swelling-reducing" traditional Chinese medicine powder combined with oral Western medicine significantly improved the joint symptoms of patients with acute gouty arthritis. Independent-samples t-tests were performed on the joint symptom scores of the three groups after treatment. P(AvsB) = 0.04, P(AvsC) < 0.001, indicating statistically significant differences. This suggests that the combination of oral Western medicine and the treatment of the present invention is more effective in addressing joint symptoms than the external application of "heat-clearing and swelling-reducing" traditional Chinese medicine powder or oral Western medicine alone.

[0205] Comparing the three groups of patients before and after treatment, statistical analysis showed significant differences in pain (P(A) <0.001, P(B) <0.001, P(C) <0.001), swelling (P(A) <0.001, P(B) <0.001, P(C) <0.001), and limited mobility (P(A) <0.001, P(B) <0.001, P(C) <0.001). This indicates that the combination of oral Western medicine and the combination of powdered "heat-clearing and swelling-reducing" traditional Chinese medicine with oral Western medicine in the present invention group can significantly improve the patients' joint pain, swelling, and limited mobility. Independent samples t-tests were performed on each of the three groups after treatment, and no statistically significant differences were found in pain improvement between any of the groups. Regarding the joint swelling score, P(AvsC) < 0.01; regarding the joint mobility limitation score, P(AvsB) = 0.02, P(AvsC) = 0.01, indicating that compared with the treatment of "clearing heat and reducing swelling" Chinese medicine powder applied externally combined with oral Western medicine and treatment of oral Western medicine alone, the treatment of the present invention combined with oral Western medicine can improve the degree of joint swelling and mobility limitation in patients.

[0206] Experimental Example 3: Typical Case

[0207] Case 1: Mr. Meng, a 32-year-old resident of Beijing, had a 10-year history of gout. On March 1, 2024, after a long-distance hike, he experienced redness, swelling, and pain in his left first metatarsophalangeal joint after washing his feet in icy stream water, making it impossible for him to bear weight. He was treated with the combination of this invention and oral Western medicine. The pain lessened after one dose, and after two days of treatment, the pain and swelling significantly decreased, allowing him to walk normally. See [link / details]. Figure 10 , Figure 11 .

[0208] Case 2: Mr. Zhang, a 28-year-old resident of Beijing, had a 5-year history of gout with intermittent attacks. He sought medical attention on June 9, 2024, after experiencing a gout attack two days following playing ice hockey. His left knee was swollen and painful, making it difficult to identify bony landmarks and causing difficulty in knee flexion and extension. After three days of treatment with the combination of this invention and oral Western medicine, the swelling significantly decreased, knee movement returned to normal, and pain was relieved. (See details...) Figure 12 , Figure 13 .

[0209] Case 3: Mr. Hu, a 38-year-old resident of Beijing, had a 3-year history of gout, with two attacks in the past 2 years. On May 13, 2024, after drinking iced beer and exercising, he experienced redness, swelling, heat, and pain in the right first metatarsophalangeal joint and dorsum of the foot, making it difficult to walk. He was treated with the combination of the formula of this invention and oral Western medicine. The pain was relieved after one day of medication, and the redness and swelling in his foot subsided after three days. Figure 14 , Figure 15 .

Claims

1. A traditional Chinese medicine composition for treating acute gouty arthritis, characterized in that, The ingredients, by weight percentage, are as follows: 5-30% nano-phase of traditional Chinese medicine, 1-5% carbomer 940, 3-12% glycerin, 0.02-0.2% sodium hyaluronate, 1-6% 1,3-butanediol, 1-8% propylene glycol, 1-8% triethanolamine, and the balance being distilled water. The traditional Chinese medicine nanophase material is made from the following raw materials in parts by weight: 0.5-8 parts of cinnamon twig, 0.5-8 parts of red peony root, 1-5 parts of ephedra, 0.5-8 parts of anemarrhena rhizome, 2-15 parts of mirabilite, 1-10 parts of gardenia fruit, and 1-8 parts of borneol. The preparation method of the traditional Chinese medicine nanoparticles includes the following steps: A. Take a dialysis bag with a relative molecular mass cutoff of 100-400, put it into distilled water containing 1-3 wt.% sodium bicarbonate and 0.5-2 mmol / L EDTA-Na2 at pH 8, boil for 5-15 minutes, cool, and store in 30-70% ethanol at 1-6℃ for later use. B. Weigh out the following ingredients according to the specified proportions: cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite, and gardenia fruit. Place them in a round-bottom flask, add 5-15 times the volume of water, soak for 20-40 minutes, reflux for 10-30 minutes, filter while hot, add 5-15 times the volume of water to the residue, reflux for 10-30 minutes, filter while hot through a 100-300 mesh filter cloth, combine the filtrates, and concentrate under reduced pressure to 0.3-1.0 g / ml to obtain the total extract of the compound Chinese medicine. C. At room temperature, centrifuge the total extract of the compound Chinese medicine from step B at 7000-10000 rpm for 20-40 min, collect the precipitate, and set aside for later use; D. Take the dialysis bag from step A, add the supernatant from step C (centrifugation), place it in a beaker containing ultrapure water, and dialyze for 20-40 minutes. Remove the sample from the dialysis bag, centrifuge at 10000-13000 rpm for 20-40 minutes, aspirate the supernatant, and combine the trace precipitate with the precipitate from step C. Repeat the above dialysis and centrifugation steps 3-6 times, combine the precipitates, and set aside for later use. E. Weigh borneol, add anhydrous ethanol to make a 5-15% borneol alcohol solution, add the precipitate combined in step D, stir well, and you will get the traditional Chinese medicine nano-phase material.

2. The traditional Chinese medicine composition for treating acute gouty arthritis according to claim 1, characterized in that, The composition by weight percentage includes: 10-20% Chinese herbal nanoparticles, 1-4% carbomer 940, 5-10% glycerin, 0.02-0.1% sodium hyaluronate, 1-4% 1,3-butanediol, 1-5% propylene glycol, 1-6% triethanolamine, and the balance being distilled water.

3. The traditional Chinese medicine composition for treating acute gouty arthritis according to claim 2, characterized in that, The composition by weight percentage includes: 15% Chinese herbal nano-phase material, 1.5% carbomer 940, 10% glycerin, 0.05% sodium hyaluronate, 2.5% 1,3-butanediol, 2.5% propylene glycol, 3.0% triethanolamine, and the balance being distilled water.

4. A traditional Chinese medicine composition for treating acute gouty arthritis according to any one of claims 1-3, characterized in that, The traditional Chinese medicine nanophase material is made from the following raw materials in parts by weight: 1-5 parts cinnamon twig, 1-5 parts red peony root, 1-3 parts ephedra, 1-5 parts anemarrhena rhizome, 3-12 parts mirabilite, 2-6 parts gardenia fruit, and 1-5 parts borneol.

5. The traditional Chinese medicine composition for treating acute gouty arthritis according to claim 4, characterized in that, The traditional Chinese medicine nanophase material is made from the following raw materials in parts by weight: 1 part cinnamon twig, 1-2 parts red peony root, 1 part ephedra, 1-2 parts anemarrhena rhizome, 5-10 parts mirabilite, 2-3 parts gardenia fruit, and 1 part borneol.

6. The traditional Chinese medicine composition for treating acute gouty arthritis according to claim 5, characterized in that... The dosage forms are gels, pastes, ointments, sprays, or plasters.

7. A method for preparing a traditional Chinese medicine composition for treating acute gouty arthritis according to any one of claims 1-6, characterized in that, Includes the following steps: (1) Preparation of nano-phase materials of traditional Chinese medicine: A. Take a dialysis bag with a relative molecular mass cutoff of 100-400, put it into distilled water containing 1-3 wt.% sodium bicarbonate and 0.5-2 mmol / L EDTA-Na2 at pH 8, boil for 5-15 minutes, cool, place in 30-70% ethanol, and store at 1-6℃ for later use. B. Weigh out the following ingredients according to the specified proportions: cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite, and gardenia fruit. Place them in a round-bottom flask, add 5-15 times the volume of water, soak for 20-40 minutes, reflux for 10-30 minutes, filter while hot, add 5-15 times the volume of water to the residue, reflux for 10-30 minutes, filter while hot through a 100-300 mesh filter cloth, combine the filtrates, and concentrate under reduced pressure to 0.3-1.0 g / ml to obtain the total extract of the compound Chinese medicine. C. At room temperature, centrifuge the total extract of the compound Chinese medicine from step B at 7000-10000 rpm for 20-40 min, collect the precipitate, and set aside for later use; D. Take the dialysis bag from step A, add the supernatant from step C (centrifugation), place it in a beaker containing ultrapure water, and dialyze for 20-40 minutes. Remove the sample from the dialysis bag, centrifuge at 10000-13000 rpm for 20-40 minutes, aspirate the supernatant, and combine the trace precipitate with the precipitate from step C. Repeat the above dialysis and centrifugation steps 3-6 times, combine the precipitates, and set aside for later use. E. Weigh borneol, add anhydrous ethanol to make a 5-15% borneol alcohol solution, add the precipitate combined in step D, stir well, and you will get the traditional Chinese medicine nano-phase material. (2) Weigh out Carbomer 940 and sodium hyaluronate respectively, add distilled water, heat and stir to make them completely swollen, then add glycerin, traditional Chinese medicine nano-phase material, 1,3-butanediol and propylene glycol, and make up the remainder with distilled water; (3) Add triethanolamine to the mixed solution in step (2) to adjust the pH to 4-7, stir slowly and evenly in the same direction until a clear, fine and uniform yellow transparent gel is formed, fill, sterilize and package to obtain the product.

8. The method for preparing a traditional Chinese medicine composition for treating acute gouty arthritis according to claim 7, characterized in that, The preparation steps of traditional Chinese medicine nanoparticles include: A. Take a dialysis bag with a relative molecular mass cutoff of 200, put it into distilled water containing 2 wt.% sodium bicarbonate and 1 mmol / L EDTA-Na2 at pH 8, boil for 10 min, cool, place in 50% ethanol, and store at 4℃ for later use. B. Weigh out the following ingredients according to the proportions: cinnamon twig, red peony root, ephedra, anemarrhena rhizome, mirabilite, and gardenia fruit. Place them in a round-bottom flask, add 12 times the volume of water and soak for 30 minutes. Reflux for 20 minutes and filter while hot. Add 10 times the volume of water to the residue and reflux for 20 minutes. Filter while hot through a 200-mesh filter cloth. Combine the filtrates and concentrate under reduced pressure to 0.5 g / ml to obtain the total extract of the compound Chinese medicine. C. At room temperature, centrifuge the total extract of the compound Chinese medicine from step B at 10,000 rpm for 30 min, collect the precipitate, and set aside for later use; D. Take the dialysis bag from step A, add the supernatant from step C after centrifugation, place it in a beaker containing ultrapure water and dialyze for 30 minutes. Take out the sample from the dialysis bag, centrifuge at 13000 rpm for 30 minutes, aspirate the supernatant, and combine the trace precipitate with the precipitate from step C. Repeat the above dialysis and centrifugation steps 3-6 times, combine the precipitates, and set aside for later use. E. Weigh borneol, add anhydrous ethanol to make a 5-12% borneol alcohol solution, add the precipitate combined in step D, stir well, and you will get the traditional Chinese medicine nanophase material.

9. Use of the traditional Chinese medicine composition according to any one of claims 1-6 in the preparation of a medicament for treating acute gouty arthritis.

10. The use according to claim 9, characterized in that... The drug is for external use only.

11. The use according to claim 10, characterized in that... The dosage form of the drug is a gel, paste, ointment, spray, or patch.

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