A topical liniment for treating psoriasis and its preparation method

Abstract

This invention relates to a topical tincture for treating psoriasis and its preparation method. The herbal formula comprises: 16-36 parts by weight of Psoralea corylifolia, 2-6 parts by weight of Cinnamomum cassia, 18-41 parts by weight of Zaocys dhumnades, 9-20 parts by weight of Bombyx mori excrement, and 9-20 parts by weight of Angelica dahurica. The above herbal formula is prepared as a tincture using 75% alcohol. Based on traditional empirical formulas and combined with the clinical symptoms of psoriasis in Traditional Chinese Medicine, this invention selects suitable herbs with photosensitive components. The formula exhibits good drug compatibility and interactions, and can be used independently or in combination with natural sunlight or ultraviolet radiation, greatly improving efficacy.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, and specifically relates to a topical liniment for treating psoriasis and its preparation method. This liniment is particularly suitable for use in conjunction with phototherapy. Background Technology

[0002] Psoriasis is a chronic, relapsing inflammatory skin disease, considered a typical immune-mediated disorder, characterized by erythematous scaling. In traditional medicine, it is known as "white lichen" or "cowhide rash." The disease progresses slowly, is prone to relapse, and negatively impacts patients' lives. The cause of psoriasis is unknown, and there is no cure; it remains a serious global problem. Western medicine considers psoriasis a polygenic hereditary disease resulting from the interaction of multiple factors, including genetic factors, immune factors, and exogenous and endogenous triggers such as infection, trauma, systemic medications, and neuropsychiatric factors. Through a common immune-mediated pathway, it ultimately leads to the proliferation of keratinocytes.

[0003] Current treatment methods for psoriasis generally include: 1. Topical medication, including both traditional Chinese medicine and Western medicine; 2. Physical therapy, including natural sunlight and ultraviolet light therapy; 3. Systemic drug therapy; 4. Combination therapy, etc.

[0004] Traditional Chinese medicine (TCM) offers diverse treatments for psoriasis. Xiao Dingyuan, a nationally renowned TCM doctor and a leading advocate of the Xiao family dermatology school in Fujian Province, developed a compound cinnamon tincture as an external treatment for psoriasis. This formula, composed of psoralea corylifolia, cinnamon, cuscuta chinensis, and tribulus terrestris, is simple yet potent, focusing on tonifying the kidneys, promoting blood circulation, moistening dryness, and dispelling wind. However, variations in the dosage of individual herbs within the formula are a significant factor affecting its efficacy, which is the subject of this invention. Summary of the Invention

[0005] The purpose of this invention is to develop a topical tincture of traditional Chinese medicine for treating psoriasis and its preparation method.

[0006] The technical solution of this invention is implemented as follows: A topical liniment for treating psoriasis, characterized in that: a traditional Chinese medicine formula: 16-36 parts by weight of Psoralea corylifolia, 2-6 parts by weight of Cinnamomum cassia, 18-41 parts by weight of Zaocys dhumnades, 9-20 parts by weight of Bombyx mori excrement, and 9-20 parts by weight of Angelica dahurica; the above traditional Chinese medicine formula is prepared into a tincture using 75% alcohol, with the amount of alcohol being 400-600 parts by weight.

[0007] A topical liniment for treating psoriasis, characterized by the following: a traditional Chinese medicine formula: 20-30 parts by weight of Psoralea corylifolia, 3-5 parts by weight of Cinnamomum cassia, 28-33 parts by weight of Zaocys dhumnades, 12-17 parts by weight of Bombyx mori excrement, and 12-17 parts by weight of Angelica dahurica; and 375-560 parts by weight of alcohol.

[0008] Furthermore, the traditional Chinese medicine formula consists of: 26 parts by weight of Psoralea corylifolia, 4 parts by weight of cinnamon, 30 parts by weight of Zaocys dhumnades, 15 parts by weight of silkworm excrement, and 15 parts by weight of Angelica dahurica; and 450-500 parts by weight of alcohol.

[0009] A method for preparing a topical ointment for treating psoriasis includes the following steps: 1. Selecting traditional Chinese medicine ingredients and alcohol; 2. Grinding the ingredients into coarse powder, with a particle size not exceeding 10 mesh; 3. Soaking the ingredients in a portion of the alcohol and stirring for at least 30 minutes to ensure all the coarse powder is in contact with and submerged in the alcohol; 4. Sealing and allowing the mixture to stand at a temperature of 10°C. 0 C-20 0 C. Soak for more than seven days in an environment with a relative humidity of 35%-75%; V. Filter and press the dregs, collect the pressed liquid, precipitate and take the clear liquid, and combine it with the filtrate to obtain the extract; VI. Add the remaining alcohol to the extract, mix well, and let it stand for 24 hours. Then take the clear liquid from the top and seal it in a light-proof container to obtain the finished liniment.

[0010] Based on traditional empirical formulas and combined with the clinical symptoms of psoriasis in traditional Chinese medicine, this invention selects suitable Chinese medicinal materials with photosensitive components. The formula has good drug compatibility and interaction, and can be used independently or in combination with natural light or ultraviolet radiation to greatly improve the efficacy. Detailed Implementation

[0011] The present invention will be further described below through specific implementation methods.

[0012] A topical tincture for treating psoriasis, formulated with the following traditional Chinese medicine ingredients: 26g of Psoralea corylifolia, 4g of Cinnamomum cassia, 30g of Zaocys dhumnades, 15g of Bombyx mori excrement, and 15g of Angelica dahurica; and 500g of alcohol. It is prepared into a tincture using the following steps.

[0013] Specific steps: 1. Select the Chinese herbal medicine ingredients and 75% alcohol; 2. Crush the herbs into coarse powder, with a particle size no larger than 10 mesh; 3. Soak the herbs in a portion of the alcohol, stirring for 30 minutes to ensure all the coarse powder is in contact with and submerged in the alcohol; 4. Seal and let stand at a temperature of 10°C. 0 C-20 0 C. Soak for seven days in an environment with a relative humidity of 35%-75%; V. Filter and press the residue, collect the pressed liquid, precipitate and take the clear liquid, and combine it with the filtrate to obtain the extract; VI. Add the remaining alcohol to the extract, mix well, and let it stand for 24 hours. Then take the clear liquid from the top and seal it in a light-proof container to make a topical liniment for psoriasis.

[0014] The clinical therapeutic effects of the above-prepared topical ointment for treating psoriasis are as follows:

[0015] Glossary: ​​The topical ointment for psoriasis of this invention is hereinafter referred to as "Compound Flavored Cinnamon Tincture";

[0016] The renowned traditional Chinese medicine doctor Xiao Dingyuan's experienced prescription is called "Compound Cinnamon Tincture".

[0017] Clinical subjects:

[0018] This study included 84 psoriasis patients who visited the Dermatology Department of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine in Fujian Province between November 2020 and June 2023. The patients included 44 males and 40 females, aged 18-65 years, with a disease duration of 4 months to 10 years. They were randomly divided into three groups using a random number table: an optimized treatment group, a treatment group with the original prescription, and a control group. The optimized treatment group consisted of 29 patients (15 males and 16 females) with a mean age of (39.82±13.28) years and a mean disease duration of (4.68±2.31) years. The original treatment group consisted of 27 patients (13 males and 14 females) with a mean age of (37.22±15.16) years and a mean disease duration of (4.33±1.91) years. The control group consisted of 28 patients (15 males and 13 females) with a mean age of (40.67±11.73) years and a mean disease duration of (4.55±2.14) years. There were no statistically significant differences in gender, age, disease duration, clinical classification, or stage of psoriasis among the three groups (P>0.05). All psoriasis patients who received treatment were informed and signed consent forms.

[0019] Treatment methods:

[0020] 1. Control group

[0021] Calcipotriol was applied topically. The method was as follows: apply a small amount to the affected skin area three times a week, following the instructions, and do not exceed 60 ml. Treatment lasted for 8 weeks. The calcipotriol used was the product of Leo Pharma Ltd. (Denmark), calcipotriol topical solution, approval number H20150664, trade name Dalixi, strength 0.005% (30 ml: 1.5 mg).

[0022] 2. Optimized treatment ratio group

[0023] Based on the previous research results of our research group, we proposed an optimized compound cinnamon tincture with the best drug ratio and concentration, applied topically in combination with natural light therapy. The optimized compound cinnamon tincture consists of psoralea corylifolia, cinnamon, black-striped snake, silkworm excrement, and angelica dahurica, prepared by adding 75% alcohol in a ratio of 26:4:30:15:15.

[0024] The patient was instructed to apply the optimized compound cinnamon tincture to the skin lesions, and to expose the lesions to natural sunlight three times a week after application. The method was to expose the medicated area to natural sunlight for 20-30 minutes between 8:00 and 10:00 in the morning after the medicated area had dried, for a total of 8 weeks.

[0025] 3. Treatment group with the original prescription ratio

[0026] The patient was given topical application of the original formula of Compound Cinnamon Tincture combined with natural sunlight therapy. The original formula of Compound Cinnamon Tincture consists of Psoralea corylifolia, Cinnamon, Cuscuta chinensis, and Tribulus terrestris, prepared by adding 75% alcohol in a ratio of 20:5:6:4.

[0027] The patient was instructed to apply compound cinnamon tincture to the lesions and expose them to natural sunlight three times a week after application. The method was to expose the medicated area to natural sunlight for 20-30 minutes between 8:00 and 10:00 in the morning after the medicated area had dried. The treatment lasted for 8 weeks.

[0028] Clinical efficacy:

[0029] The disease course was recorded before the start of treatment and at weeks 2, 4, 6 and 8 after treatment. The recorded indicators included: 1. Psoriasis Area and Severity Index (PASI); 2. Self-Assessment of Pruritus Symptoms (VAS); 3. Dermatological Quality of Life Index (DLQI).

[0030] The efficacy was evaluated according to the established assessment criteria, and the experimental results were analyzed using SPSS 25.0. The total effective rate of the optimized compound cinnamon tincture combined with natural light therapy was 93.10% (27 / 29), the total effective rate of the original compound cinnamon tincture combined with light therapy was 81.48% (22 / 27), and the total effective rate of the control group treated with calcipotriol was 71.43% (19 / 28). Compared with the original compound treatment group, the optimized treatment group showed a statistically significant difference in the pre- and post-treatment efficacy before and after treatment (P<0.05) using the χ2 test; the optimized treatment group also showed a statistically significant difference in the total effective rate compared with the control group (P<0.05) using the χ2 test. This indicates that all three groups can effectively improve the clinical symptoms of psoriasis, but the optimized treatment group is superior to the original compound treatment group and the control group, as shown in Table 1.

[0031]

[0032] Recurrence rate:

[0033] At the 8th week follow-up after the end of treatment, 2 cases were lost to follow-up in the optimized formula treatment group, 2 cases were lost to follow-up in the original formula treatment group, and 3 cases were lost to follow-up in the control group. After excluding the lost to follow-up cases, the recurrence rate at the 8th week follow-up after the end of treatment in the optimized formula treatment group was 22.22%, which was lower than the recurrence rates in the original formula treatment group and the control group (26.92% and 28.00%, respectively). The difference was statistically significant (P<0.05), as shown in Table 2.

[0034]

[0035] Summarize:

[0036] External application of traditional Chinese medicine is an important treatment method for psoriasis. The *Surgical Secrets* states regarding psoriasis, "These sores cannot be quickly healed with just one or two doses of qi-tonifying and blood-tonifying medicine; therefore, external treatment is essential," clearly indicating the stubborn and difficult-to-treat nature of this disease and emphasizing the importance of external treatment. Research on topical traditional Chinese medicine preparations for psoriasis treatment is beneficial for directly relieving symptoms and improving psoriatic skin lesions through local treatment, thereby enhancing the therapeutic effect. [7] Professor Xiao Dingyuan, a renowned traditional Chinese medicine doctor, is the seventh-generation inheritor of Fuzhou Xiao Family Surgery, a Fuzhou intangible cultural heritage. Based on over 60 years of medical experience, and considering the characteristics of psoriasis, such as its course, season of onset, and location, he proposed the pathogenesis concept of "kidney deficiency as the root cause, blood stasis as the manifestation." [2] For external application, a self-prepared "compound cinnamon tincture" (containing psoralea, cinnamon, dodder seed, and tribulus terrestris in a ratio of 20:5:6:4, with 75% alcohol) has been used and has shown excellent clinical efficacy.

[0037] Formulation of topical liniment for psoriasis and mouse experiments.

[0038] Through clinical observation, the research team found that psoriasis patients in Fujian Province with a long history of the disease often exhibit symptoms such as fatigue, dark erythema, slightly sticky scales, heaviness and discomfort in the limbs, cold extremities, and a deep, slippery pulse. The etiology can be attributed to external factors such as the lingering and difficult-to-treat dampness caused by geographical factors; and internal factors such as emotional distress leading to internal stagnation, dietary indiscretion resulting in phlegm accumulation, or prolonged illness and excessive use of cold-natured medications damaging the spleen and kidney yang. Therefore, patients with pre-existing spleen and kidney yang deficiency, leading to internal dampness, coupled with external dampness invasion, eventually experience blood stasis in the skin and meridians, resulting in stagnation of qi and blood and the onset of the disease. Thus, under the influence of multiple pathogenic factors, including internal and external factors, and the unique climate and seasons of Fujian Province, the psoriasis patients in Fujian Province often present with skin stasis caused by blood stasis and phlegm accumulation. Therefore, based on Professor Xiao Dingyuan's theoretical foundation and combined with clinical observation and practice, the research team proposed a treatment method of warming yang, dispelling dampness, and unblocking the meridians. This was further modified clinically by applying a compound cinnamon tincture with added ingredients (main components: psoralea corylifolia, cinnamon, silkworm excrement, black-striped snake, angelica dahurica, and 75% alcohol). This compound cinnamon tincture draws inspiration from the "Black Snake Wind-Expelling Decoction" formula. [9]The formula uses Psoralea corylifolia and cinnamon as the chief ingredients. Psoralea corylifolia has the function of tonifying the kidney and warming the spleen. The Compendium of Materia Medica states that "cinnamon strengthens tendons and bones and unblocks blood vessels." Psoralea corylifolia combined with the pungent, sweet and hot cinnamon can tonify fire and assist yang, warm the kidney and unblock the meridians, and circulate throughout the body. Zaocys dhumnades and silkworm excrement are the assistant ingredients. Zaocys dhumnades can not only dispel wind and dampness and unblock the meridians, but the Kaibao Materia Medica also states that it "treats various wind-related itching, rashes, scabies, and numbness of the skin." It can relieve itching and detoxify. Silkworm excrement can also remove dampness and turbidity, and invigorate blood and unblock the meridians. The two herbs combined can remove stubborn skin numbness and coldness caused by spleen and stomach yang deficiency. Angelica dahurica is the adjuvant ingredient. The Compendium of Materia Medica states that it is "the main medicine of Yangming, so it can also treat blood diseases." It can enter the lung and stomach meridians, so it is used as an adjuvant ingredient to dispel wind and dry dampness, invigorate blood and promote tissue regeneration. Alcohol is the guiding ingredient. The above herbs are soaked in alcohol to enhance their function of invigorating blood and unblocking the meridians. The "Wan Family Secret Surgical Heart Method" states that external treatment "must also consider the season, diagnose the pulse, differentiate between deficiency and excess, determine the severity, assess the course of the disease, and use the appropriate treatment accordingly, so as not to cause premature death." Therefore, combining treatment with seasonal sunlight exposure can help to strengthen Yang, dispel dampness, and unblock the meridians. At the same time, the Chinese herbal ingredients used in the optimized compound Zhi Gui Ding (a type of herbal tincture) have also made some progress in modern pharmacological research regarding their mechanism of action against psoriasis. For example, 8-methoxypsoralen and isopsoralen in Psoralea corylifolia, imperatorin in Angelica dahurica, pheophytin in silkworm excrement, and cinnamamide in cinnamon may all play a role in regulating psoriatic lesions. One of their mechanisms may involve photosensitizing Chinese herbal medicines inducing apoptosis of cells in psoriatic lesions, inhibiting the proliferation of keratinocytes, and delaying the secretion of inflammatory factors.

[0039] Previous clinical studies have shown that traditional Chinese medicine formulas have demonstrated efficacy in treating psoriasis. In our previous research, we conducted orthogonal drug compatibility experiments to compare and evaluate changes in the Psoriasis Area and Severity Index (PASI) score, epidermal thickness in skin tissue pathological sections, and changes in tissue interleukin-23 (IL-23) and interleukin-17 (IL-17) in mice after intervention. This led us to determine the optimal compatibility ratio for the compound herbal tincture: 26:4:30:15:15 for Psoralea corylifolia, Cinnamomum cassia, Zaocys dhumnades, Bombyx mori excrement, and Angelica dahurica. The screening of the compatibility ratios for the traditional Chinese medicine formula and a brief description of the mouse experiments are as follows:

[0040] 1. Laboratory animals

[0041] Ninety male BALB / c mice, 6-8 weeks old and 18-20g, were housed individually.

[0042] 2. Main drugs

[0043] Compound Zhi Gui Tincture; Imiquimod Cream (Sichuan Mingxin Pharmaceutical Co., Ltd., batch number 21010340); Vaseline (Nanchang Baiyun Pharmaceutical Co., Ltd., batch number 20200810, batch number 20220317), etc.

[0044] 3. Compound Cinnamon Tincture with Added Ingredients

[0045] After classifying the compound cinnamon tincture into principal, assistant, and adjuvant drugs, different compatibility schemes were generated through orthogonal drug compatibility experiment L9 (33), denoted as S1-S9. For details of the specific grouping, please refer to Table 3.

[0046]

[0047] The weight units in the table above are grams. The specific proportions of each component can also be regarded as part of the embodiment. The classic components J1 and J2 in the table above are the same, except that J1 has no light intervention and J2 has light intervention, and so on.

[0048] 4. Experimental Grouping

[0049] All mice were kept in an environment with 90%-95% humidity. They were anesthetized by intraperitoneal injection of sodium pentobarbital (80 mg / kg), and the hair on their backs was shaved to create an exposed area of ​​approximately 2 cm × 3 cm. They were housed individually in cages. Ninety male BALB / c mice were randomly divided into 15 groups of 6 mice each. The compound preparation regimen for the treatment group with added cinnamon tincture is shown in Table 4.

[0050]

[0051] 5. Experimental Results

[0052] The effects of Compound Jiawei Zhigui Tincture on imiquimod-induced psoriasis-like skin lesions in mice were investigated. The presence of erythema, scale thickness, and skin thickening in the Compound Jiawei Zhigui Tincture intervention group were all less pronounced than in the model group (M1) and the model-light-intervention group (M2) at the same time point. On day 14, compared to the model group, the erythema in the Compound Jiawei Zhigui Tincture intervention group was lighter in color, with fewer scales and less thickening. After day 14, the erythema in the model group gradually subsided, scales fell off, leaving only some fine debris, and the skin gradually became smooth. The skin lesions in the Compound Jiawei Zhigui Tincture intervention group also began to lessen from the levels observed on days 7-8, as shown in Table 5.

[0053]

[0054] The effects of Compound Jiawei Zhigui Tincture on the levels of IL-17 and IL-23 in the skin tissue of imiquimod-induced psoriasis-like mice were investigated. The levels of IL-17 and IL-23 in the skin tissue of the model group mice were significantly increased, approximately 1.5 times that of the normal group. The levels of IL-17 and IL-23 in the skin tissue of all groups treated with Compound Jiawei Zhigui Tincture were significantly lower than those in the model group (P<0.01). Among them, the levels in group S8 were 1 / 3 of those in the normal model group. Compared with other groups, the levels of IL-17 and IL-23 were significantly reduced (P<0.01), as shown in Table 6.

[0055]

[0056] By using different concentrations of compound cinnamon tincture with different combinations, different wavelengths of light, and different durations of light exposure, experiments were conducted on mice to screen out the optimal treatment regimen for psoriasis: "compound cinnamon tincture with optimized ratio combined with natural light exposure." The combined treatment regimen involved patients applying the optimized compound cinnamon tincture to the lesions, followed by natural sunlight exposure three times a week after application, and then exposing the treated area to natural sunlight for 20-30 minutes between 8:00-10:00 AM after drying.

[0057] Applying the experimental results to this clinical trial showed that the optimized compound cinnamon tincture can directly contact and act on the skin lesions, directly relieving symptoms and improving skin lesions through local treatment, thereby enhancing the therapeutic effect. Compared with the original formula treatment group and the control group, the optimized compound cinnamon tincture had a slightly better effect on the local areas of psoriasis (stasis skin syndrome), more effectively reducing the psoriasis area and severity index (PASI), relieving itching symptoms, improving the dermatology quality of life index (DLQI), and delaying the recurrence rate. Secondly, the optimized compound cinnamon tincture was formulated based on the specific conditions of previous experiments, possessing high controllability and transdermal absorption, enabling rapid absorption and penetration at the lesion site, thereby accelerating the therapeutic effect. Thirdly, compared with the control group, the optimized compound cinnamon tincture typically uses natural plant materials, exhibiting better safety and tolerability, with lower toxicity and side effects, less likelihood of systemic adverse reactions, and reduced risks of allergies and overtreatment.

Claims

1. A psoriasis treating external use liniment, characterized by: Traditional Chinese medicine formula: Fructus Psoraleae 16-36 parts by weight, Cinnamomi Cassiae 2-6 parts by weight, Rhabdophis nigrscens 18-41 parts by weight, Silkworm excrement 9-20 parts by weight, Radix Angelicae Dahuricae 9-20 parts by weight; The above traditional Chinese medicine formula is made into tincture with 75% alcohol, and the alcohol amount is 400-600 parts by weight.

2. A psoriasis treating external use liniment, characterized by: Traditional Chinese medicine formula: Fructus Psoraleae 20-30 parts by weight, Cinnamomi Cassiae 3-5 parts by weight, Rhabdophis nigrscens 28-33 parts by weight, Silkworm excrement 12-17 parts by weight, Radix Angelicae Dahuricae 12-17 parts by weight; alcohol amount 375-560 parts by weight.

3. The therapeutic psoriasis external use liniment according to claim 1 or 2, characterized in that: Traditional Chinese medicine formula: Fructus Psoraleae 26 parts by weight, Cinnamomi Cassiae 4 parts by weight, Rhabdophis nigrscens 30 parts by weight, Silkworm excrement 15 parts by weight, Radix Angelicae Dahuricae 15 parts by weight; alcohol amount 450-500 parts by weight.

4. A method for preparing the therapeutic external liniment for psoriasis according to claim 3, characterized by: The method comprises the following steps:

1. selecting traditional Chinese medicine and alcohol; 2. crushing into coarse powder, the size of the coarse powder is not more than 10 meshes; 3. soaking the traditional Chinese medicine in part of the alcohol and stirring, the stirring time is not less than 30 minutes, so that all the coarse powder is contacted with the alcohol and immersed; 4. sealing and standing, the temperature is 10 0 C-20 0 C. The relative humidity is 35%-75%, and the soaking time is more than 7 days; 5. filtering and squeezing the residue, collecting the precipitate of the squeezed liquid, taking the clear liquid, and combining the filtrate to obtain the soaking liquid; 6. adding the remaining alcohol into the soaking liquid and mixing, then standing for 24 hours, taking the upper clear liquid, sealing in a light-shielding container, and obtaining the finished product.

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