Traditional Chinese medicine composition for treating ulcerative colitis and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating ulcerative colitis. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 5-30 parts of cortex phellodendri, 5-30 parts of herba artemisiae scopariae, 6-18 parts of fructus gardeniae, 6-18 parts of cortex fraxini, 6-18 parts of herba artemisiae annuae, 5-30 parts of poria cocos, 5-30 parts of rhizoma atractylodis macrocephalae, 5-10 parts of fructus evodiae, 5-10 parts of fructus amomi rotundus, 5-10 parts of gypsum and 0.2-8 parts of liquorice root. The traditional Chinese medicine composition provided by the invention can be prepared into a patch for treating ulcerative colitis, especially for treating damp-heat intestine accumulation type ulcerative colitis. The traditional Chinese medicine composition provided by the invention can be transdermally absorbed, so that a first-pass effect is avoided, and gastrointestinal stimulation is reduced; the intestinal immunity and flora are regulated in a multi-target manner, and the recurrence rate is reduced; acupuncture point stimulation enhances local drug concentration and improves curative effect.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and in particular relates to a traditional Chinese medicine composition for treating ulcerative colitis and application thereof. Background Art

[0002] Ulcerative colitis (UC) is a chronic, nonspecific inflammatory intestinal disease characterized by bloody mucus in the stool, abdominal pain, and diarrhea. The etiology of UC remains unclear, but studies suggest a clear correlation with genetics, immunity, and environmental factors.

[0003] Researchers have discovered that an immune imbalance between helper T cells (Th17) and regulatory T cells (Treg) plays a key role in the pathogenesis of ulcerative colitis (UC). The intestinal microbiome comprises the intestinal flora, intestinal epithelial cells, and the mucus layer. Maintaining a stable intestinal microbiome requires a balanced intestinal flora and a balanced Th / Treg balance. Studies have shown that an imbalance between helper T cells (Th17) and regulatory T cells (Treg), which differentiate from CD4+ T cells, can contribute to the development of UC. Studies have confirmed that within the intestinal immune environment, regulatory T cells (Treg) can regulate the activity of Th17 cells and sIgA, thereby regulating intestinal immune function. This balance is crucial for maintaining intestinal immune homeostasis. Disturbances in the intestinal microbiome can lead to abnormal expression of inflammatory factors and abnormal bacterial metabolites, which in turn affect intestinal epithelial cells, disrupt the epithelial barrier, and lead to decreased intestinal mucosal barrier function, inducing an inflammatory response and promoting the development of UC.

[0004] In recent years, treatment strategies and research advances for UC have continuously evolved, and the goal of UC treatment has continuously evolved, from the initial goal of "symptom improvement" to "clinical remission" and "steroid-free remission," to the currently recognized "mucosal healing," and with the future goal of achieving "histological healing." The STRIDE study proposed that the latest treatment targets should include steroid-free remission and mucosal healing as short-term goals, and altering the natural course of the disease and preventing adverse outcomes such as intestinal damage as long-term goals. Modern medical treatments for UC primarily include 5-aminosalicylic acid, glucocorticoids, immunomodulatory drugs, and biologic drugs. 5-aminosalicylic acid is used to treat mild to moderate UC, while moderate to severe UC can be treated with therapies targeting specific inflammatory pathways, such as monoclonal antibodies targeting TNFα, α4β7 integrin, IL-12, and IL-23, and small molecule inhibitors of JAKs and S1P. Furthermore, new treatment options are still under investigation. Studies have shown that the intestinal bacterial metabolite 12-ketolithocholic acid can prevent UC exacerbations by promoting VDR expression, inhibiting ILC3 secretion of the proinflammatory cytokine IL-17A, and suppressing colitis exacerbation in mice. However, current clinical UC treatments have problems such as hormone dependence, adverse reactions and drug resistance, which still need to be solved.

[0005] While modern medical treatments are diverse, they still have some shortcomings. Traditional Chinese Medicine (TCM), with its unique advantages, offers new insights and approaches for the treatment of UC. TCM treatment of UC features multiple components, multiple targets, multiple pathways, and a holistic approach. It boasts a rich therapeutic approach, few adverse reactions, and widespread application. TCM primarily works by regulating inflammatory cytokines, the intestinal microbiota, and the immune system, while also protecting the intestinal mucosa. The advantages of TCM in treating UC include: ① Significant efficacy: TCM demonstrates significant advantages in inducing clinical remission, synergizing with Western medications to enhance efficacy and reduce toxicity, improving patient quality of life, and preventing relapse. ② Low relapse rate: TCM treatment can reduce the relapse rate of UC. ③ Minimal toxicity and side effects: Compared to Western medications, TCM has fewer toxic side effects. ④ Multi-target regulation: TCM exerts its therapeutic effects by modulating multiple signaling pathways, demonstrating comprehensive, balanced regulation across multiple targets, multiple links, and multiple systems. ⑤ Intestinal microbiota regulation: Combining TCM with Western medication not only enhances efficacy but also enhances the activity of probiotics in the gut, inhibiting the growth of pathogenic bacteria, and accelerating the repair of the intestinal mucosal barrier. Currently, commonly used Chinese patent medicines include Hudi Enteric-coated Capsules, Wuwei Kushen Enteric-coated Capsules, Bawei Xilei Powder, and Fufang Kushen Colon-coated Capsules. These Chinese patent medicines have demonstrated efficacy in treating ulcerative colitis, particularly in improving clinical symptoms, reducing relapse rates, and improving patients' quality of life, with minimal side effects. The advantages of Traditional Chinese Medicine (TCM) in treating ulcerative colitis lie in its holistic approach and personalized treatment, enabling tailored treatment tailored to each patient's specific condition. While TCM is highly effective in treating ulcerative colitis, oral administration of TCM is associated with a first-pass effect, and patient compliance needs to be improved. Summary of the Invention

[0006] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating ulcerative colitis.

[0007] Another object of the present invention is to provide a use of the traditional Chinese medicine composition in the preparation of a medicine for treating ulcerative colitis.

[0008] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0009] A first aspect of the present invention provides a traditional Chinese medicine composition for treating ulcerative colitis, which is prepared from the following components in parts by weight: 5-30 parts of Phellodendron amurense, 5-30 parts of Artemisia capillaris, 6-18 parts of Gardenia jasminoides, 6-18 parts of Fraxinus fraxinus, 6-18 parts of Artemisia annua, 5-30 parts of Poria cocos, 5-30 parts of Atractylodes macrocephala, 5-10 parts of Evodia rutaecarpa, 5-10 parts of white cardamom, 5-10 parts of gypsum, and 0.2-8 parts of liquorice.

[0010] Most preferably, the Chinese medicine composition for treating ulcerative colitis is made from the following components in parts by weight:

[0011] 15 parts of Phellodendron chinense, 15 parts of Artemisia capillaris, 12 parts of Gardenia jasminoides, 12 parts of Fraxinus fraxinus, 12 parts of Artemisia annua, 15 parts of Poria cocos, 15 parts of Atractylodes macrocephala, 8 parts of Evodia rutaecarpa, 8 parts of White Amomum villosum, 8 parts of Gypsum, and 3 parts of Licorice.

[0012] Most preferably, the Chinese medicine composition for treating ulcerative colitis is made from the following components in parts by weight:

[0013] 15 parts of Phellodendron chinense, 15 parts of Artemisia capillaris, 12 parts of Gardenia jasminoides, 12 parts of Fraxinus fraxinus, 12 parts of Artemisia annua, 15 parts of Poria cocos, 15 parts of Atractylodes macrocephala, 7.5 parts of Evodia rutaecarpa, 7.5 parts of white cardamom, 7.5 parts of Gypsum, and 0.6 part of Licorice.

[0014] Most preferably, the Chinese medicine composition for treating ulcerative colitis is made from the following components in parts by weight:

[0015] 5 parts of Phellodendron chinense, 5 parts of Artemisia capillaris, 18 parts of Gardenia jasminoides, 18 parts of Fraxinus fraxinus, 18 parts of Artemisia annua, 5 parts of Poria, 5 parts of Atractylodes macrocephala, 10 parts of Evodia rutaecarpa, 10 parts of White Amomum villosum, 10 parts of Gypsum, and 8 parts of Licorice.

[0016] Most preferably, the Chinese medicine composition for treating ulcerative colitis is made from the following components in parts by weight:

[0017] 30 parts of Phellodendron chinense, 30 parts of Artemisia capillaris, 6 parts of Gardenia jasminoides, 6 parts of Fraxinus chinensis, 6 parts of Artemisia annua, 30 parts of Poria cocos, 30 parts of Atractylodes macrocephala, 5 parts of Evodia rutaecarpa, 5 parts of White Amomum villosum, 5 parts of Gypsum, and 2 parts of Licorice.

[0018] Most preferably, the Chinese medicine composition for treating ulcerative colitis is made from the following components in parts by weight:

[0019] 18 parts of Phellodendron chinense, 18 parts of Herba Artemisiae Scopariae, 15 parts of Gardeniae, 15 parts of Cortex Fraxini, 15 parts of Artemisia annua, 18 parts of Poria, 18 parts of Atractylodes macrocephala, 8 parts of Evodia rutaecarpa, 8 parts of White Amomum villosum, 8 parts of Gypsum, and 4 parts of Radix Glycyrrhizae.

[0020] In the traditional Chinese medicine composition for treating ulcerative colitis, the mass ratio of Phellodendron chinense to Artemisia capillaris is 1:1, and the mass ratio of Gardenia jasminoides, Fraxinus frassin and Artemisia annua is 1:1:1.

[0021] The second aspect of the present invention provides a use of the traditional Chinese medicine composition in preparing a medicament for treating ulcerative colitis.

[0022] The ulcerative colitis particularly refers to ulcerative colitis of the damp-heat accumulation type.

[0023] The third aspect of the present invention provides a patch, which is made of a composite matrix, a thick paste extracted from Phellodendron chinense, Artemisia capillaris, Gardenia jasminoides, Fraxinus fraxinus, Artemisia annua, Poria cocos, Atractylodes macrocephala, Evodia rutaecarpa, and white cardamom in a traditional Chinese medicine composition for treating ulcerative colitis, gypsum, and ultrafine powder made from liquorice, wherein the composite matrix includes acrylic pressure-sensitive adhesive, liquid paraffin, azone, menthol, and glycerin.

[0024] The mass ratio of the acrylic pressure-sensitive adhesive, liquid paraffin, azone, menthol and glycerin is 8:4:1:1:2.

[0025] The mass ratio of the composite matrix to the thick paste is 1:1-2, preferably 1:1.4.

[0026] A fourth aspect of the present invention provides a method for preparing the patch, comprising the following steps:

[0027] Add 5-10 times (preferably 8 times) of purified water to soak Phellodendron amurense, Artemisia capillaris, Gardenia jasminoides, Fraxinus chinensis, Artemisia annua, Poria cocos, Atractylodes macrocephala, Evodia rutaecarpa, and Cardamomum villosum in water for 20-40 minutes, preferably 30 minutes, and decoct for 2-4 times (preferably 3 times), each time for 0.5-2 hours (preferably 1 hour). Combine the extracts and concentrate under reduced pressure until the relative density reaches 1.1-1.4 (preferably 1.25) to obtain a thick paste.

[0028] Grind gypsum and liquorice into ultrafine powder and pass through a 200-mesh sieve to obtain ultrafine powder;

[0029] Mix the thick paste with the ultrafine powder, add glycerin and purified water to form phase A;

[0030] Heat the acrylic pressure-sensitive adhesive and liquid paraffin to 40-60°C (preferably 50°C) and mix well to obtain phase B;

[0031] Slowly add phase A to phase B and mix, add azone and menthol, and stir evenly to obtain an ointment;

[0032] The ointment was evenly applied on the base material, and the ointment was covered with release paper (silicone oil paper, 3M™ 1022, thickness 0.08 mm) on the top layer. The ointment was dried (hot air circulation drying at a temperature of 45°C for 25 minutes) and cut to obtain a patch.

[0033] The base material is a medical non-woven backing material (Xinlong Holding Co., Ltd., size 60 cm × 100 cm × 0.2 mm).

[0034] The ointment is evenly coated on the base material with a thickness of 0.1 to 0.5 mm (preferably 0.2 mm).

[0035] The fifth aspect of the present invention provides a use of the patch in preparing a medicament for treating ulcerative colitis.

[0036] In the traditional Chinese medicine composition of the present invention, the monarch drugs Phellodendron chinense and Artemisia capillaris clear away heat and dampness; the assistant drugs Gardenia jasminoides, Fraxinus chinensis and Artemisia annua enhance the heat-clearing and dampness-eliminating effects; the adjuvant drugs Poria cocos and Atractylodes macrocephala invigorate the spleen and eliminate dampness, preventing the monarch drug from damaging the spleen and stomach; Evodia rutaecarpa and White cardamom warm the middle and resolve turbidity, preventing the monarch drug from being too cold; the auxiliary drugs Gypsum gypsum and Licorice harmonize the medicinal properties.

[0037] The properties, flavor, meridians and functions of the Chinese medicinal raw materials of the present invention are as follows:

[0038] Phellodendron chinense: Nature and flavor: bitter, cold. Meridians entered: Kidney, bladder, and large intestine. Indications: Clears heat and dampness, purges fire and detoxifies, and reduces asthenic fever. It is used for damp-heat diarrhea, jaundice, leukorrhea, and stranguria caused by heat; bone steaming, fatigue, night sweats, and spermatorrhea; sores, swelling, and itching caused by eczema.

[0039] Artemisia capillaris: Nature and flavor: Bitter, pungent, slightly cold. Meridians entered: Spleen, Stomach, Liver, and Gallbladder. Benefits: Clears damp-heat, promotes bile secretion, and reduces jaundice. It is primarily used to treat damp-heat jaundice and dysuria, and is also commonly used for itching caused by eczema.

[0040] Gardenia: Nature and flavor: bitter, cold. Meridians entered: Heart, Lung, and Triple Burner. Indications: Purges heat and relieves restlessness, clears heat and dampness, cools the blood and detoxifies. Used for restlessness due to febrile illness, damp-heat jaundice, painful and astringent stranguria caused by blood in the intestines, and vomiting and bleeding caused by blood heat; externally used for sores, swellings, sprains, and pain.

[0041] Cortex Fraxini: Nature and flavor: bitter, astringent, cold. Meridians entered: Liver, Gallbladder, and Large Intestine. Efficacy: Clears heat and dampness, astringes and stops dysentery, stops leukorrhea, and improves eyesight. Indications: Damp-heat diarrhea, leukorrhea, and genital itching, red, swollen, and painful eyes due to liver heat, and pannus.

[0042] Artemisia annua: Nature and flavor: bitter, pungent, cold. Meridians entered: Liver and Gallbladder. Indications: Clears heat from internal heat, relieves bone steaming, relieves summer heat, stops malaria, and reduces jaundice. It is used for yin damage caused by pathogenic warming, nighttime fever and morning coolness, yin deficiency fever, bone steaming and fatigue fever, summer heat exogenous infection, malaria-induced chills and fever, and damp-heat jaundice.

[0043] Poria: Nature and flavor: Sweet, mild, neutral. Meridians entered: Spleen, Heart, and Kidney. Benefits: Promotes diuresis and eliminates dampness, strengthens the spleen, and calms the mind. Indications: Edema, oliguria, phlegm and fluid retention, dizziness and palpitations, spleen deficiency, poor appetite, loose stools and diarrhea, restlessness, palpitations, and insomnia.

[0044] Atractylodes macrocephala: Nature and flavor: sweet, bitter, warm. Meridians entered: Spleen and Stomach. Indications: Strengthens the spleen and replenishes Qi, eliminates dampness and promotes diuresis, stops sweating, and stabilizes the fetus. It is used for spleen deficiency, poor appetite, abdominal distension and diarrhea, phlegm and fluid retention, dizziness and palpitations, edema, spontaneous sweating, and fetal restlessness.

[0045] Evodia rutaecarpa: Properties and flavors: Pungent, bitter, hot; slightly toxic. Meridians entered: Liver, spleen, stomach, and kidney. Indications: Dispels cold and relieves pain, reduces adverse reactions and stops vomiting, and boosts yang and stops diarrhea. Indications: Headaches, abdominal pain, and hernias caused by cold stagnation in the liver meridian; vomiting caused by stomach cold, and diarrhea caused by cold deficiency; and externally treats mouth sores and eczema.

[0046] White Cardamom: Nature and Flavor: Pungent, Warming. Meridians Entered: Lung, Spleen, and Stomach. Indications: Eliminates dampness and promotes Qi circulation, warms the middle and stops vomiting, and stimulates appetite and aids digestion. It is used for dampness and turbidity in the middle, abdominal distension, indigestion, the initial onset of damp-heat syndrome, and vomiting caused by stomach cold.

[0047] Gypsum: Nature and flavor: Sweet, pungent, extremely cold. Meridians entered: Lung and Stomach. Indications: Clears heat and purges fire, relieves restlessness and thirst, and astringes and promotes tissue regeneration (calcined). Raw gypsum is used for high fever, thirst, wheezing and coughing due to lung heat, and excessive stomach fire. Calcined gypsum is used externally for persistent ulcers, itchy eczema, and burns caused by water or fire.

[0048] Licorice: Nature and flavor: Sweet, neutral. Meridians entered: Heart, Lung, Spleen, and Stomach. Indications: Tonifies the spleen and replenishes Qi, clears heat and detoxifies, eliminates phlegm and relieves cough, relieves pain, and harmonizes various medicinal herbs. It is used for spleen and stomach deficiency, fatigue, palpitations, shortness of breath; cough with excessive phlegm, carbuncles, sores, and cramps and pain in the limbs. It is often used as an adjuvant in prescriptions.

[0049] Due to the adoption of the above technical solution, the present invention has the following advantages and beneficial effects:

[0050] The Chinese medicine composition provided by the present invention, formulated as a patch, is used to treat ulcerative colitis, particularly in patients with damp-heat accumulation in the intestines according to Traditional Chinese Medicine (TCM) criteria. The patch achieves efficient and safe treatment through the following core advantages:

[0051] The Chinese medicine composition provided by the present invention is efficiently absorbed through the skin, avoiding the first-pass effect and gastrointestinal irritation: the patch of the present invention adopts advanced transdermal drug delivery technology. The key penetration enhancer, azone, is scientifically formulated into the matrix, which significantly enhances the ability of the active ingredients of the drug to penetrate the skin barrier. The drug is directly absorbed into the blood through the skin capillaries, completely avoiding the "first-pass effect" of the liver faced by oral administration, and greatly improving the bioavailability of the drug. At the same time, this method of administration completely bypasses the diseased gastrointestinal tract, fundamentally eliminating the direct stimulation of the drug to ulcers and inflamed intestinal mucosa, significantly improving the safety of medication and patient compliance, and is especially suitable for patients in the active stage with gastrointestinal symptoms such as nausea, vomiting, and abdominal pain.

[0052] The traditional Chinese medicine composition provided by the present invention synergistically regulates multiple targets, improving immune balance and microbiome, and reducing recurrence. The formula selects herbs such as Phellodendron amurense, Artemisia capillaris, Gardenia jasminoides, Fraxinus chinensis, and Artemisia annua to clear heat, dampness, and toxins. It also incorporates Poria cocos and Atractylodes macrocephala to invigorate the spleen and dispel dampness, Evodia rutaecarpa and Cardamomum villosum to warm the middle and dissolve dampness and promote qi circulation, Gypsum to clear heat and purge fire, and Licorice to harmonize the herbs. These herbs work together to clear heat and dampness, invigorate the spleen and stomach, and harmonize qi and blood. Modern pharmacological studies have shown that the active ingredients in the formula act at multiple targets in the intestine. On the one hand, they modulate local intestinal immune responses, particularly by correcting the imbalanced Th17 / Treg cell ratio, alleviating excessive inflammatory responses. On the other hand, they regulate the intestinal microbiome, inhibiting the overgrowth of harmful bacteria, promoting the colonization of beneficial bacteria, and repairing intestinal barrier function. This multi-pathway, multi-target synergistic effect not only effectively controls acute symptoms but also fundamentally improves the intestinal environment, significantly reducing the recurrence rate of the disease.

[0053] The Chinese medicine composition provided by the present invention is delivered through acupuncture point targeting, which enhances meridian conduction and increases local concentration: the patch of the present invention is designed to be applied to specific acupuncture points (such as Tianshu, Guanyuan, Dachangshu, Zusanli, and Pishu). This is not only a simple selection of drug delivery sites, but also combines the theory of meridians in traditional Chinese medicine. While the drug ingredients are absorbed through the skin, they stimulate the meridians by stimulating the acupuncture points, guiding the drug effects to act precisely on the abdomen and related internal organs (especially the intestines and spleen and stomach), achieving a dual therapeutic effect of drug + acupuncture point stimulation. This targeted effect can significantly increase the effective concentration of the drug in the local diseased intestine, enhance the efficacy of clearing heat and dampness, strengthening the spleen and stomach, while improving the microcirculation of the abdomen and intestines, promoting the dissipation of inflammation and tissue repair, thereby synergistically improving the overall therapeutic effect.

[0054] The traditional Chinese medicine composition provided by the present invention is formulated into a patch using an advanced formulation process, ensuring sustained release, comfort, and stability. The patch is prepared using a rigorous scientific process. The medicinal materials are decocted and concentrated to produce a thick paste. Gypsum and licorice are ultrafinely ground into powder, significantly increasing the specific surface area and promoting dissolution and transdermal absorption. These two ingredients are then mixed with glycerin and purified water to form phase A. The matrix utilizes a high-performance acrylic pressure-sensitive adhesive as the primary adhesive material, with liquid paraffin added to adjust viscosity. This composite matrix, when combined with the drug, provides excellent sustained-release adhesive properties, ensuring sustained and stable release and transdermal delivery of the drug ingredient. The addition of menthol effectively alleviates skin irritation and increases patient comfort. Glycerin provides moisturizing and plasticizing properties, maintaining the patch's flexibility and skin moisturization, facilitating drug penetration. The final ointment is precisely coated onto medical non-woven fabric using automated equipment, covered with release paper, gently dried, die-cut, and packaged in nitrogen-filled aluminum-plastic bags, maximizing drug stability and shelf life.

[0055] In summary, the Chinese medicine composition provided by the present invention is made into a Chinese medicine patch. Through an innovative transdermal administration route, a carefully formulated multi-target compound, a synergistic mechanism combined with acupoint stimulation, and advanced sustained-release transdermal preparation technology (including key process points such as azone to promote penetration, acrylic pressure-sensitive adhesive to sustain release, menthol to soothe, glycerin to moisturize, ultrafine grinding to enhance absorption, and nitrogen-filled packaging for stability), it provides a special external treatment solution for patients with damp-heat accumulation in the intestine type ulcerative colitis that is efficient, safe, convenient, and can reduce recurrence. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] Figure 1 Schematic diagram of the colon mucosa of Case 1 before and after treatment. DETAILED DESCRIPTION

[0057] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. Those skilled in the art should understand that the following specific description is illustrative rather than restrictive and should not be used to limit the scope of protection of the present invention.

[0058] Example 1

[0059] A Chinese medicine composition for treating ulcerative colitis is prepared from the following components:

[0060] Phellodendron amurense 15g, Artemisia capillaris 15g, Gardenia 12g, Qinpi 12g, Artemisia annua 12g, Poria 15g, Atractylodes macrocephala 15g, Evodia rutaecarpa 8g, White cardamom 8g, Gypsum 8g, Licorice 3g.

[0061] A method for preparing a patch comprises the following steps:

[0062] According to the above ratio, add 8 times purified water to Phellodendron amurense, Artemisia capillaris, Gardenia jasminoides, Qinpi, Artemisia annua, Poria cocos, Atractylodes macrocephala, Evodia rutaecarpa, and White Cardamom, soak for 30 minutes, decoct and extract 3 times, each time for 1 hour, combine the extracts, and concentrate under reduced pressure to a relative density of 1.25 to obtain 45g of thick paste.

[0063] Gypsum and licorice were ultrafinely ground and passed through a 200-mesh sieve to obtain 11 g of ultrafine powder.

[0064] Mix 45g of thick paste with 11g of ultrafine powder, add 4g of glycerin and 32g of purified water to form phase A;

[0065] The model of the acrylic pressure-sensitive adhesive is 3MTM 1577, the model of the liquid paraffin is USP grade white oil 70#, and the azone is a pharmaceutical grade azone with a purity of 99%.

[0066] Heat 16 g of acrylic pressure-sensitive adhesive and 8 g of liquid paraffin to 50°C and mix well to obtain phase B;

[0067] Slowly add phase A to phase B and mix, then add 2 g of azone and 2 g of menthol and stir well to obtain 120 g of ointment;

[0068] Using a fully automatic coating and laminating machine (DC3082, Changzhou Jianzhi Machinery Factory), 120 g of ointment was evenly coated on a medical non-woven fabric backing material (Xinlong Holding Co., Ltd., size 60 cm × 100 cm × 0.2 mm) with a coating thickness of 0.2 mm (ointment dosage of about 2 g / patch), and the ointment was covered with a release paper (silicone oil paper, 3M TM 1022, 0.08 mm thick), dried (hot air circulation drying at 45°C for 25 minutes), and cut into patches (10 cm × 10 cm) using a circular die cutter. The patches were placed in an aluminum-plastic bag and protected with nitrogen to obtain 60 traditional Chinese medicine patches for the treatment of ulcerative colitis.

[0069] The mass ratio of the acrylic pressure-sensitive adhesive, liquid paraffin, azone, menthol and glycerin is 8:4:1:1:2.

[0070] The mass ratio of the composite matrix to the thick paste is 1:1.4.

[0071] Example 2

[0072] A Chinese medicine composition for treating ulcerative colitis is prepared from the following components:

[0073] Phellodendron amurense 15g, Artemisia capillaris 15g, Gardenia 12g, Qinpi 12g, Artemisia annua 12g, Poria 15g, Atractylodes macrocephala 15g, Evodia rutaecarpa 7.5g, White cardamom 7.5g, Gypsum 7.5g, Licorice 0.6g.

[0074] The patch was prepared according to the method of Example 1.

[0075] Example 3

[0076] A Chinese medicine composition for treating ulcerative colitis is prepared from the following components:

[0077] Phellodendron 5g, Artemisia capillaris 5g, Gardenia 18g, Qinpi 18g, Artemisia annua 18g, Poria 5g, Atractylodes macrocephala 5g, Evodia rutaecarpa 10g, White cardamom 10g, Gypsum 10g, Licorice 8g.

[0078] The patch was prepared according to the method of Example 1.

[0079] Example 4

[0080] A Chinese medicine composition for treating ulcerative colitis is prepared from the following components:

[0081] Phellodendron 30g, Artemisia capillaris 30g, Gardenia 6g, Qinpi 6g, Artemisia annua 6g, Poria 30g, Atractylodes macrocephala 30g, Evodia rutaecarpa 5g, White cardamom 5g, Gypsum 5g, Licorice 2g.

[0082] The patch was prepared according to the method of Example 1.

[0083] Example 5

[0084] A Chinese medicine composition for treating ulcerative colitis is prepared from the following components:

[0085] Phellodendron amurense 18g, Artemisia capillaris 18g, Gardenia 15g, Qinpi 15g, Artemisia annua 15g, Poria 18g, Atractylodes macrocephala 18g, Evodia rutaecarpa 8g, White cardamom 8g, Gypsum 8g, Licorice 4g.

[0086] The patch was prepared according to the method of Example 1.

[0087] Example 6

[0088] Clinical trial plan

[0089] 1. General Information

[0090] A total of 120 patients with ulcerative colitis (UC) of the damp-heat accumulation type who visited the anorectal outpatient department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated with Shanghai University of Traditional Chinese Medicine between January 2024 and January 2025 were randomly divided into an observation group (60 patients) treated with acupoint plaster therapy combined with mesalazine and a control group (60 patients) treated with oral mesalazine alone. There were no statistically significant differences in baseline data, including age, gender, and disease duration, between the two groups (P > 0.05).

[0091] 2. Diagnostic criteria

[0092] Western medicine diagnosis: refer to the "Guidelines for the Diagnosis and Treatment of Ulcerative Colitis in China (2023·Xi'an)".

[0093] ① Clinical manifestations: Persistent or recurrent diarrhea, bloody and mucousy stools, abdominal pain, and tenesmus. Severe cases may also present with varying degrees of systemic symptoms, including weight loss, fever, tachycardia, fatigue, and even nausea and vomiting. The course of illness typically ranges from 4 to 6 weeks, though some cases may last less than 4 weeks. However, diarrhea lasting less than 6 weeks should be carefully differentiated from infectious enteritis. Common extraintestinal manifestations of UC include joint damage (such as peripheral arthritis and spondyloarthritis), mucocutaneous manifestations (such as oral ulcers, erythema nodosum, and pyoderma gangrenosum), ocular lesions (such as iritis, scleritis, and uveitis), hepatobiliary disorders (such as fatty liver, primary sclerosing cholangitis, and cholelithiasis), and thromboembolic disease. Complications include toxic megacolon, intestinal perforation, massive lower gastrointestinal bleeding, intestinal intraepithelial neoplasia, and carcinoma.

[0094] ② Colonoscopic manifestations: Under colonoscopy, UC lesions often start from the rectum, are continuous and diffusely distributed, and the lesions are mostly superficial. Active stage: Mild inflammation: erythema, mucosal congestion and disappearance of vascular texture. Moderate inflammation: disappearance of vascular morphology, bleeding adheres to the mucosal surface, erosion, often accompanied by a rough granular appearance and increased mucosal fragility (contact bleeding). Severe inflammation: spontaneous mucosal bleeding and ulcers. Normal mucosal appearance can be seen in the remission period, and some patients may have pseudopolyp formation or scar-like changes. Patients with long-term disease: Mucosal atrophy leads to disappearance of the colon bag morphology, intestinal stenosis, and inflammatory (pseudo) polyps. Patients with cytomegalovirus infection may see irregular, deep chisel-like or longitudinal ulcers, some with large patches of mucosal loss.

[0095] ③ Mucosal biopsy: During the active phase, the following may be observed: 1) Diffuse, acute, and chronic inflammatory cell infiltration within the lamina propria, including neutrophils, lymphocytes, plasma cells, and eosinophils, particularly neutrophil infiltration between epithelial cells (i.e., cryptitis), which may even lead to the formation of crypt abscesses. Increased plasma cells at the crypt base are considered the earliest light microscopic feature of ulcerative colitis. 2) Altered crypt architecture, with irregular crypt size and morphology, branching, budding, and disordered arrangement, and a decrease in goblet cells. 3) Mucosal surface erosion, shallow ulceration, and granulation tissue may be observed. During the remission phase, mucosal erosion or ulcer healing may be observed; neutrophil infiltration of the lamina propria may decrease or disappear, and chronic inflammatory cell infiltration may decrease. Alterations in crypt architecture may be retained, such as branching, reduction, or atrophy of crypts, and Paneth cell metaplasia may be observed distal to the splenic flexure of the colon.

[0096] ④ Imaging manifestations: UC imaging manifestations are characterized by continuous, symmetrical, uniform, mild thickening of the colon wall and a smooth serosal surface. In the early stages of UC, the mucosa is affected and there may be no abnormal imaging manifestations. As the disease progresses, multiple small ulcers and inflammatory polyps may be shown on the mucosal surface. Some patients may also show intestinal stenosis, intestinal rigidity, shallowing or disappearance of colonic pouches, and intestinal shortening.

[0097] TCM diagnostic criteria: Refer to the "Expert Consensus on Diagnosis and Treatment of Ulcerative Colitis with Integrated Traditional Chinese and Western Medicine" published by the Chinese Society of Integrated Traditional Chinese and Western Medicine in 2023 for the diagnosis of damp-heat intestinal syndrome in ulcerative colitis, as follows:

[0098] ① Main symptoms: abdominal pain, diarrhea, mucus, pus and blood in stool; tenesmus and burning sensation in the anus.

[0099] ② Secondary symptoms: fever; short and dark urine; dry and bitter mouth; bad breath.

[0100] ③Tongue and pulse: red tongue, yellow and greasy tongue coating, slippery and rapid pulse.

[0101] This syndrome can be diagnosed if two or more main symptoms and two or more secondary symptoms are present at the same time.

[0102] 3. Intervention measures

[0103] Observation Group:

[0104] ① Mesalazine enteric-coated tablets 1g orally 3 times a day;

[0105] ② The patch prepared in Example 1 was applied to acupuncture points such as Tianshu, Guanyuan, Dachangshu, Zusanli, and Pishu, one patch per day for 6 hours each time, for 4 consecutive weeks.

[0106] Control group: Oral mesalazine enteric-coated tablets 1g tid for 4 consecutive weeks.

[0107] 4. Observation indicators

[0108] Main Outcome Measures: Modified Mayo score and Traditional Chinese Medicine syndrome score.

[0109] The Mayo scoring criteria are shown in Table 1:

[0110] Table 1

[0111] The scoring criteria for TCM syndromes refer to the section "Guidelines for Clinical Research of New TCM Drugs for the Treatment of Chronic Nonspecific Ulcerative Colitis" in the "Guidelines for Clinical Research of New TCM Drugs" (2002). The scoring principles are as follows: the main symptoms are divided into none, mild, moderate, and severe according to the severity, with scores of 0, 3, 6, and 9 respectively. The secondary symptoms are divided into none, mild, moderate, and severe according to the severity, with scores of 0, 1, 2, and 3 respectively. The main symptoms include: abdominal pain, diarrhea, mucus, pus, and blood in the stool; tenesmus and anal burning. Secondary symptoms include: fever; short and dark urine; dry and bitter mouth; and bad breath. The specific scoring criteria are shown in Table 2:

[0112] Table 2

[0113] Secondary indicators: peripheral blood IL10, IL17, CRP, and ESR levels.

[0114] Safety indicators: liver and kidney function, skin allergic reactions.

[0115] Experimental results:

[0116] 1. The comparison results of the modified Mayo score before and after treatment are shown in Table 3. From the data in Table 3, it can be seen that after treatment, the modified Mayo score of the observation group was significantly lower than that of the control group (P < 0.01).

[0117] Table 3

[0118] Note: Compared with before treatment, P < 0.05; *Compared with the control group after treatment, P < 0.01.

[0119] 2. The results of TCM syndrome efficacy evaluation are shown in Table 4. As can be seen from the table, the total effective rate of the observation group was 93.3% (56 / 60), which was significantly higher than that of the control group (76.7% (46 / 60)) (P < 0.05).

[0120] Table 4

[0121] 3. The results of changes in inflammatory factors are shown in Tables 5 to 8. As can be seen from Tables 5 and 6, after treatment, the IL17 level in the observation group decreased significantly, the IL10 level increased, and the inflammation control was better than that in the control group (P < 0.05).

[0122] Table 5

[0123] Table 6

[0124] Note: Compared with before treatment, *P < 0.05; **Compared with the control group after treatment, P < 0.01.

[0125] The comparison results of CRP levels of the two groups of patients before and after treatment are shown in Table 7:

[0126] Table 7

[0127] The comparison results of ESR levels of the two groups of patients before and after treatment are shown in Table 8:

[0128] Table 8

[0129] Note: **Compared with the control group after treatment, P < 0.01.

[0130] 4. Safety Evaluation

[0131] Two patients (3.3%) in the observation group experienced mild itching at the application site, which did not affect treatment; four patients (6.7%) in the control group experienced gastrointestinal discomfort. Liver and kidney function remained normal in both the observation and control groups.

[0132] The comparison results of liver function indicators of the two groups of patients before and after treatment are shown in Table 9:

[0133] Table 9

[0134] The comparison results of renal function indicators of the two groups of patients before and after treatment are shown in Table 10:

[0135] Table 10

[0136] Note: There were no statistically significant differences in all liver and kidney function indicators among the three groups (P > 0.05).

[0137] Typical clinical cases

[0138] Case 1: A 42-year-old male with a 3-year history of ulcerative colitis presented with abdominal pain and 68 episodes of mucus and bloody stools daily. Colonoscopy revealed diffuse erosions extending from the rectum to the sigmoid colon. Patients were treated with the patch prepared in Example 1, applied daily to the Tianshu and Dachangshu points for 6 hours each time. Mesalazine enteric-coated tablets 1g were also taken orally 3 times a day. After 4 weeks of treatment, bowel movement frequency decreased to 2 per day, mucus and bloody stools disappeared, and the Mayo Clinic score decreased from 5 to 2. No recurrence was observed during 6-month follow-up. Figure 1 Schematic diagrams of the colon mucosa of Case 1 before and after treatment, wherein the upper figure is a schematic diagram before treatment; the lower figure is a schematic diagram after treatment. It can be seen from the figures that the colon mucosa healed after 4 weeks of treatment with the patch prepared in Example 1 of the present invention combined with mesalazine enteric-coated tablets.

[0139] Case 2: A 38-year-old female patient with active ulcerative colitis (UC) had elevated IL-17 (42 pg / mL). The patch prepared in Example 1 was applied daily to the Tianshu and Dachangshu points for 6 hours each time. Mesalazine enteric-coated tablets 1g were taken orally 3 times a day. After 4 weeks of treatment, IL-17 decreased to 15 pg / mL. Colonoscopy showed mucosal healing, and the Traditional Chinese Medicine (TCM) syndrome score decreased from 12 to 6.

[0140] Case 3: A 45-year-old male with a 2-year history of ulcerative colitis. Main complaints: abdominal pain, diarrhea (5-6 times / day), and mucus, pus, and blood in the stool (4-5 times / day). Colonoscopy revealed congestion and edema of the rectal and sigmoid colon mucosa, with scattered erosions (modified Mayo score 7). The patch prepared in Example 1 was applied daily (6 hours / day) to the Tianshu, Guanyuan, Dachangshu, and Zusanli points, combined with oral mesalamine 1g 3 times a day. After 4 weeks of treatment, the abdominal pain disappeared, and bowel movements were 1-2 times / day without mucus, pus, or blood in the stool. The modified Mayo score decreased to 2, and the Traditional Chinese Medicine syndrome score decreased from 10 to 3. A follow-up colonoscopy showed mucosal healing, and no recurrence was observed during the 3-month follow-up.

[0141] The patch prepared in Example 1 of the present invention combined with mesalazine enteric-coated tablets can significantly improve the clinical symptoms of patients with damp-heat intestinal UC, regulate the Th17 / Treg immune balance, and reduce the level of inflammatory factors. The total effective rate is 93.3%, and the safety is good, providing an innovative solution for the external treatment of UC.

[0142] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as above in terms of a preferred embodiment, it is not intended to limit the present invention. Any technician familiar with the present invention can make slight changes or modifications to equivalent embodiments using the above-mentioned technical contents without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the solution of the present invention.

Claims

1. A Chinese medicine composition for treating ulcerative colitis, characterized in that: The invention is prepared from the following components in parts by weight: 5-30 parts of Phellodendron amurense, 5-30 parts of Artemisia capillaris, 6-18 parts of Gardenia jasminoides, 6-18 parts of Fraxinus fraxinus, 6-18 parts of Artemisia annua, 5-30 parts of Poria cocos, 5-30 parts of Atractylodes macrocephala, 5-10 parts of Evodia rutaecarpa, 5-10 parts of White cardamom, 5-10 parts of Gypsum, and 0.2-8 parts of Licorice root. In the traditional Chinese medicine composition for treating ulcerative colitis, the mass ratio of Phellodendron chinense to Artemisia capillaris is 1:1, and the mass ratio of Gardenia jasminoides, Fraxinus frassin and Artemisia annua is 1:1:

1.

2. The Chinese medicine composition for treating ulcerative colitis according to claim 1, characterized in that The traditional Chinese medicine composition for treating ulcerative colitis is prepared from the following components in parts by weight: 15 parts of phellodendron amurense, 15 parts of capillaris, 12 parts of gardenia jasminoides, 12 parts of qinpi, 12 parts of artemisia annua, 15 parts of poria, 15 parts of atractylodes macrocephala, 8 parts of evodia rutaecarpa, 8 parts of white cardamom, 8 parts of gypsum, and 3 parts of liquorice.

3. The Chinese medicine composition for treating ulcerative colitis according to claim 1, characterized in that The traditional Chinese medicine composition for treating ulcerative colitis is prepared from the following components in parts by weight: 15 parts of phellodendron amurense, 15 parts of scutellaria baicalensis, 12 parts of gardenia jasminoides, 12 parts of qinpi cortex, 12 parts of artemisia annua, 15 parts of poria, 15 parts of atractylodes macrocephala, 7.5 parts of evodia rutaecarpa, 7.5 parts of white cardamom, 7.5 parts of gypsum, and 0.6 parts of liquorice.

4. The Chinese medicine composition for treating ulcerative colitis according to claim 1, characterized in that The traditional Chinese medicine composition for treating ulcerative colitis is prepared from the following components in parts by weight: 5 parts of phellodendron amurense, 5 parts of capillaris, 18 parts of gardenia jasminoides, 18 parts of qinpi, 18 parts of artemisia annua, 5 parts of poria, 5 parts of atractylodes macrocephala, 10 parts of evodia rutaecarpa, 10 parts of white cardamom, 10 parts of gypsum, and 8 parts of liquorice.

5. The Chinese medicine composition for treating ulcerative colitis according to claim 1, characterized in that The traditional Chinese medicine composition for treating ulcerative colitis is prepared from the following components in parts by weight: 30 parts of Phellodendron amurense, 30 parts of Artemisia capillaris, 6 parts of Gardenia jasminoides, 6 parts of Fraxinus fraxinus, 6 parts of Artemisia annua, 30 parts of Poria cocos, 30 parts of Atractylodes macrocephala, 5 parts of Evodia rutaecarpa, 5 parts of White Amomum villosum, 5 parts of Gypsum, and 2 parts of Licorice.

6. The Chinese medicine composition for treating ulcerative colitis according to claim 1, characterized in that The traditional Chinese medicine composition for treating ulcerative colitis is prepared from the following components in parts by weight: 18 parts of Phellodendron amurense, 18 parts of Artemisia capillaris, 15 parts of Gardenia jasminoides, 15 parts of Fraxinus fraxinus, 15 parts of Artemisia annua, 18 parts of Poria cocos, 18 parts of Atractylodes macrocephala, 8 parts of Evodia rutaecarpa, 8 parts of White Amomum villosum, 8 parts of Gypsum, and 4 parts of Licorice.

7. Use of the traditional Chinese medicine composition according to any one of claims 1 to 6 in the preparation of a medicament for treating ulcerative colitis.

8. A patch, characterized in that The patch is made of a composite matrix, a thick paste extracted from Phellodendron chinense, Artemisia capillaris, Gardenia jasminoides, Fraxinus fraxinus, Artemisia annua, Poria cocos, Atractylodes macrocephala, Evodia rutaecarpa, and White Cardamom in the traditional Chinese medicine composition for treating ulcerative colitis according to any one of claims 1 to 6, gypsum, and ultrafine powder made from liquorice, wherein the composite matrix includes acrylic pressure-sensitive adhesive, liquid paraffin, azone, menthol, and glycerin.

9. A method for preparing the patch according to claim 8, characterized in that: The following steps are involved: Soak Phellodendron amurense, Artemisia capillaris, Gardenia jasminoides, Fraxinus chinensis, Artemisia annua, Poria cocos, Atractylodes macrocephala, Evodia rutaecarpa, and White Cardamom in 5-10 times purified water, decoct and extract 2-4 times, each time for 0.5-2 hours, combine the extracts, and concentrate under reduced pressure until the relative density is 1.1-1.4 to obtain a thick paste; Grind gypsum and liquorice into ultrafine powder and pass through a 200-mesh sieve to obtain ultrafine powder; Mix the thick paste with the ultrafine powder, add glycerin and purified water to form phase A; Heat the acrylic pressure-sensitive adhesive and liquid paraffin to 40-60°C and mix well to obtain phase B; Slowly add phase A to phase B and mix, add azone and menthol, and stir evenly to obtain an ointment; The ointment is evenly coated on the base material, the upper layer of the ointment is covered with release paper, dried, and cut to obtain a patch.

10. Use of the patch prepared by the method according to claim 9 in preparing a medicament for treating ulcerative colitis.

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