TWI610679B - Use of an ethanol extract of chinese herb and a pharmaceutical composition containing the ethanol extract of chinese herb and a steroid - Google Patents

Use of an ethanol extract of chinese herb and a pharmaceutical composition containing the ethanol extract of chinese herb and a steroid Download PDF

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TWI610679B
TWI610679B TW105139426A TW105139426A TWI610679B TW I610679 B TWI610679 B TW I610679B TW 105139426 A TW105139426 A TW 105139426A TW 105139426 A TW105139426 A TW 105139426A TW I610679 B TWI610679 B TW I610679B
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skin diseases
chinese herbal
herbal medicine
ethanol extract
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TW201821095A (en
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潘一紅
溫淑芳
呂居勳
姚心然
莊凱安
林士弘
李明翰
謝岱儒
許博堯
吳信頡
呂亦晃
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財團法人工業技術研究院
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Abstract

本發明提供一種中草藥萃取物用於製備治療皮膚疾病之藥物的用途，其中該中草藥萃取物的一製備原料包括甘草、柴胡、黃芩、五味子與芍藥。 The invention provides a Chinese herbal medicine extract for use in preparing a medicine for treating skin diseases, wherein a preparation raw material of the Chinese herbal medicine extract includes licorice, bupleurum, scutellaria baicalensis, Schisandra chinensis and peony.

Description

中草藥乙醇萃取物之用途與含此中草藥乙醇萃取物 與類固醇之醫藥組成物 Chinese herbal medicine ethanol extract and its use Pharmaceutical composition with steroids

本發明係關於一種中草藥萃取物之用途與含此中藥萃取物與類固醇之醫藥組成物。 The invention relates to the use of a Chinese herbal medicine extract and a medicinal composition containing the Chinese medicine extract and a steroid.

皮膚疾病為全球最常見的疾病，大約有1/3的人口於其一生中會出現一種病理性皮膚問題，而在於健康照護支出中，皮膚相關醫療支出也高達25%。 Skin disease is the most common disease in the world. About 1/3 of the population will have a pathological skin problem in their lifetime, and skin care medical expenses are up to 25% in health care expenditures.

皮膚疾病分成四大類，分別為皮膚炎(例如，過敏性和接觸性)、癌症(例如，黑色素瘤)、免疫疾病(例如，乾癬)以及感染性皮膚疾病(例如，細菌，真菌和病毒感染)。 Skin diseases fall into four broad categories: dermatitis (e.g., allergic and contact), cancer (e.g., melanoma), immune diseases (e.g., psoriasis), and infectious skin diseases (e.g., bacterial, fungal, and viral infections) .

外用類固醇已被廣泛使用於各類皮膚疾病，尤其是異位性皮膚炎與乾癬，而於嚴重之皮膚炎病患，其類固醇使用劑量更高。許多被歸類於類固醇(steroid)之化合物，例如倍他米松(betamethasone)或氫化波尼松(prednisolone)對於治療發炎性疾病的效果非常好，然而，這些化合物長期使用卻也可能造成病患的皮膚萎縮。病患若於類固醇治療期間出現皮膚萎縮之現象，則一般被認為是類固醇反應者(steroid responders)。皮膚萎縮對於已經 然而，即使是正常皮膚，在長期使用類固醇的情形下，亦會出現皮膚損傷之副作用。 Topical steroids have been widely used in various skin diseases, especially atopic dermatitis and psoriasis, and in severe dermatitis patients, the dosage of steroids is higher. Many compounds classified as steroids, such as betamethasone or prednisolone, are very effective in treating inflammatory diseases. However, the long-term use of these compounds may also cause disease in patients. Skin atrophy. Patients with skin atrophy during steroid treatment are generally considered steroid responders. Skin atrophy for already However, even with normal skin, the side effects of skin damage can occur with long-term steroid use.

因此，類固醇之安全替代藥物的研發及/或如何維持外用類固醇治療之療效並減少副作用是一個重要議題。 Therefore, the development of safe alternatives to steroids and / or how to maintain the efficacy of topical steroid therapy and reduce side effects is an important issue.

本發明提供一種中草藥萃取物用於製備治療皮膚疾病之藥物的用途，其中該中草藥萃取物的一製備原料包括甘草、柴胡、黃芩、五味子與芍藥。 The invention provides a Chinese herbal medicine extract for use in preparing a medicine for treating skin diseases, wherein a preparation raw material of the Chinese herbal medicine extract includes licorice, bupleurum, scutellaria baicalensis, Schisandra chinensis and peony.

本發明還提供一種中草藥萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該中草藥萃取物的一製備原料包括甘草、柴胡、黃芩、五味子與芍藥。 The invention also provides a Chinese herbal medicine extract for use in preparing a medicament for improving the side effects of steroids for treating skin diseases, wherein a raw material for the preparation of the Chinese herbal medicine extract includes licorice, bupleurum, scutellariae, schisandra and paeonia lactiflora.

本發明另提供一種減緩皮膚疾病之醫藥組成物，包括：一中藥萃取物，其中該中草藥萃取物的一製備原料包括甘草、柴胡、黃芩、五味子以及芍藥；以及一類固醇，其中該中藥萃取物具有降低該類固醇所產生之副作用的功效及/或相較於單獨使用該類固醇具有降低該類固醇所需之有效劑量的功效。 The present invention also provides a medicinal composition for slowing skin diseases, including: a Chinese medicine extract, wherein a raw material for preparing the Chinese herbal medicine extract includes licorice root, Bupleurum chinensis, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora; and a steroid, wherein the Chinese medicine extract It has the effect of reducing the side effects produced by the steroid and / or the effect of reducing the effective dose required for the steroid compared to using the steroid alone.

第1A圖顯示，於咪喹莫特(imiquimod,IMQ)誘導之類乾癬動物模式實驗中，控制組、對照組與四個實驗組之小鼠的皮膚照片。 FIG. 1A shows photographs of skins of mice in a control group, a control group, and four experimental groups in an animal model experiment of psoriasis induced by imiquimod (IMQ).

第1B圖顯示於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與四個實驗組之小鼠之IL-17A、IL-6、TNF-α與S100A7的基因表現量。 Figure 1B shows the expression levels of IL-17A, IL-6, TNF-α, and S100A7 genes in mice of the control group, control group, and four experimental groups in an animal model experiment of psoriasis induced by imiquimod.

第2A圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，對照組與三個實驗組(PT-A(100mg)軟膏處理組、PT-A-1(100mg)軟膏處理組、PT-A-2(100mg)軟膏處理組)之小鼠的皮膚照片。 Figure 2A shows that in an animal model experiment of psoriasis induced by imiquimod, the control group and three experimental groups (PT-A (100 mg) ointment-treated group, PT-A-1 (100 mg) ointment-treated group, PT -A-2 (100 mg) ointment-treated mice) skin photos.

第2B圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與三個實驗組(PT-A(100mg)軟膏處理組、PT-A-1(100mg)軟膏處理組、PT-A-2(100mg)軟膏處理組)之小鼠之脫屑加發紅的嚴重程度評分。 Fig. 2B shows that in an animal model experiment of psoriasis induced by imiquimod, the control group, the control group, and the three experimental groups (PT-A (100 mg) ointment treatment group, PT-A-1 (100 mg) ointment treatment) Group, PT-A-2 (100 mg) ointment treated group) mice were scored for the severity of desquamation and redness.

第3圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與實驗組(PT-A-DS(100mg/kg)腹腔注射處理組)之小鼠的皮膚照片及皮膚樣本之蘇木素-伊紅(hematoxylin and eosin)染色結果。 Figure 3 shows skin photographs of mice in the control group, control group, and experimental group (PT-A-DS (100mg / kg) intraperitoneal injection treatment group) in an animal model experiment of psoriasis induced by imiquimod. Hematoxylin and eosin staining results of skin samples.

第4A圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與兩個實驗組(PT-A(10mg)軟膏處理組與PT-A(100mg)軟膏處理組)之小鼠的皮膚照片。 Figure 4A shows the control group, control group, and two experimental groups (PT-A (10 mg) ointment-treated group and PT-A (100 mg) ointment-treated group) in an animal model experiment of psoriasis induced by imiquimod. Photo of mouse skin.

第4B圖顯示於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與兩個實驗組(PT-A(10mg)軟膏處理組與PT-A(100mg)軟膏處理組)之小鼠之IL-17A、IL-23與IL-22的基因表現量。 Figure 4B shows the control group, control group, and two experimental groups (PT-A (10 mg) ointment-treated group and PT-A (100 mg) ointment-treated group) in an animal model experiment of psoriasis induced by imiquimod. Gene expression of IL-17A, IL-23 and IL-22 in mice.

第4C圖顯示於咪喹莫特誘導之類乾癬動物模式實驗中，對照組與實驗組(PT-A(100mg)軟膏處理組)之小鼠之以CD68、CD4、Neutrophil、Ki-67及CD31抗體進行免疫組織染色的結果。 Figure 4C shows CD68, CD4, Neutrophil, Ki-67, and CD31 of mice in the control group and the experimental group (PT-A (100mg) ointment-treated group) in an animal model experiment of psoriasis induced by imiquimod. Results of immunohistochemical staining of antibodies.

第5A圖顯示，於1-氟-2,4-二硝基苯(1-fluoro-2,4-dinitrobenzene,DNFB)誘導動物接觸性皮膚炎模式 實驗中，控制組、正對照組與實驗組(PT-A(50mg)軟膏處理組)之小鼠耳朵的增加厚度。 Figure 5A shows a model of contact dermatitis induced by 1-fluoro-2,4-dinitrobenzene (DNFB) in animals In the experiment, the ears of the mice in the control group, the positive control group, and the experimental group (PT-A (50 mg) ointment treated group) increased in thickness.

第5B圖顯示，於1-氟-2,4-二硝基苯誘導動物接觸性皮膚炎模式實驗中，控制組、正對照組與實驗組(PT-A(50mg)軟膏處理組)之小鼠發炎部分皮膚樣本之照片與CD4免疫組織染色分析的結果。 Fig. 5B shows that in the 1-fluoro-2,4-dinitrobenzene-induced animal contact dermatitis model experiment, the control group, the positive control group, and the experimental group (PT-A (50mg) ointment-treated group) were smaller. Photographs of skin samples from inflamed rats and results of CD4 immunohistochemical analysis.

第6A圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與三組個實驗組(PT-A(100mg)軟膏處理組、Rinderon-V(0.06%，台灣鹽野義)軟膏處理組以及Daivonex(0.005%,LEO Pharma)軟膏處理組)之小鼠的皮膚照片。 Figure 6A shows that in an animal model experiment of psoriasis induced by imiquimod, the control group, control group, and three experimental groups (PT-A (100 mg) ointment-treated group, Rinderon-V (0.06%, Taiwan salt) Ye Ye) ointment-treated group and Daivonex (0.005%, LEO Pharma) ointment-treated mice) skin photos.

第6B圖顯示於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與三組實驗組(PT-A(100mg)軟膏處理組、Rinderon-V(0.06%，台灣鹽野義)軟膏處理組以及Daivonex(0.005%,LEO Pharma)軟膏處理組)之小鼠之IL-17A、IL-6、TNF-α與S100A7的基因表現量。 Figure 6B shows the control group, control group, and three groups of experimental groups (PT-A (100mg) ointment-treated group, Rinderon-V (0.06%, Shiinoi, Taiwan) in an experimental model of psoriasis induced by imiquimod. ) Gene expression levels of IL-17A, IL-6, TNF-α and S100A7 in mice of ointment-treated group and Daivonex (0.005%, LEO Pharma) ointment-treated mice).

第7A圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組(IMQ)、對照組(IMQ+媒劑)與三個實驗組(IMQ+BD(類固醇)軟膏處理組、IMQ+BD+PT-A軟膏處理組(25mg)與Daivobet(LEO Pharma)軟膏處理組)之小鼠的皮膚照片。 Figure 7A shows that in an animal model experiment of psoriasis induced by imiquimod, the control group (IMQ), the control group (IMQ + vehicle), and the three experimental groups (IMQ + BD (steroid) ointment treatment group, IMQ + Skin photographs of mice in the BD + PT-A ointment treatment group (25 mg) and Daivobet (LEO Pharma) ointment treatment group).

第7B圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與三個實驗組(BD(類固醇)軟膏處理組、BD+PT-A軟膏處理組(25mg)與Daivobet(LEO Pharma)軟膏處理組)之小鼠 之脫屑加發紅的嚴重程度評分。 Fig. 7B shows that in an animal model experiment of psoriasis induced by imiquimod, the control group, the control group, and the three experimental groups (BD (steroid) ointment-treated group, BD + PT-A ointment-treated group (25 mg), and Daivobet (LEO Pharma) ointment-treated mice) Scoring and redness severity scores.

第7C圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與三個實驗組(BD(類固醇)軟膏處理組、BD+PT-A軟膏處理組(25mg)與Daivobet(LEO Pharma)軟膏處理組)之小鼠皮膚樣本之蘇木素-伊紅(hematoxylin and eosin)染色結果。 Figure 7C shows that in an animal model experiment of psoriasis induced by imiquimod, the control group, the control group, and the three experimental groups (BD (steroid) ointment-treated group, BD + PT-A ointment-treated group (25mg), and Daivobet (LEO Pharma) ointment treatment group) mouse skin samples were stained with hematoxylin and eosin.

第7D圖顯示，於咪喹莫特誘導之類乾癬動物模式實驗中，控制組、對照組與三個實驗組(BD(類固醇)軟膏處理組、BD+PT-A軟膏處理組(25mg)與Daivobet(LEO Pharma)軟膏處理組)之以Ki-67抗體進行免疫組織染色的結果。 Figure 7D shows that in the imiquimod-induced psoriasis animal model experiment, the control group, the control group, and the three experimental groups (BD (steroid) ointment-treated group, BD + PT-A ointment-treated group (25mg), and Daivobet (LEO Pharma) ointment treatment group) The results of immunohistochemical staining with Ki-67 antibody.

第8A-1與8A-2圖顯示控制組(媒劑(vehicle))以及五個實驗組(氟輕松(fluocinonide)(0.05%；中效類固醇)軟膏處理組、氟輕松+PT-A(0.25%)軟膏處理組(PT-A比氟輕松之重量比為5：1)、氟輕松+PT-A(5%)軟膏處理組(PT-A比氟輕松之重量比為100：1)、PT-A(5%)軟膏處理組以及丙酸氯氟美松(clobetasol propionate)(0.05%)軟膏處理組)之小鼠的皮膚照片。 Figures 8A-1 and 8A-2 show the control group (vehicle) and five experimental groups (fluocinonide (0.05%; intermediate-acting steroids) ointment treatment group, fluocinolone + PT-A (0.25 %) Ointment treatment group (PT-A to fluocinolone weight ratio is 5: 1), Fluocinolone + PT-A (5%) ointment treatment group (PT-A to fluocinolone weight ratio is 100: 1), Skin photographs of mice in the PT-A (5%) ointment treated group and clobetasol propionate (0.05%) ointment treated group).

第8B-1與8B-2圖顯示控制組(媒劑)以及五個實驗組(氟輕松(0.05%；中效類固醇)軟膏處理組、氟輕松+PT-A(0.25%)軟膏處理組(PT-A比氟輕松之重量比為5：1)、氟輕松+PT-A(5%)軟膏處理組(PT-A比氟輕松之重量比為100：1)、PT-A(5%)軟膏處理組以及丙酸氯氟美松(0.05%)軟膏處理組)之小鼠的皮膚樣本的蘇木素-伊紅染色結果。 Figures 8B-1 and 8B-2 show the control group (vehicle) and the five experimental groups (fluocinolone (0.05%; intermediate-acting steroid) ointment treatment group, fluocinolone + PT-A (0.25%) ointment treatment group ( The weight ratio of PT-A to fluocinolone is 5: 1), the fluorine treatment + PT-A (5%) ointment treatment group (the weight ratio of PT-A to fluocinolone is 100: 1), PT-A (5% ) Results of hematoxylin-eosin staining of skin samples from mice treated with ointment and clofluxamone propionate (0.05%).

第8C圖顯示控制組(媒劑)以及五個實驗組(氟輕松(0.05%； 中效類固醇)軟膏處理組、氟輕松+PT-A(0.25%)軟膏處理組(PT-A比氟輕松之重量比為5：1)、氟輕松+PT-A(5%)軟膏處理組(PT-A比氟輕松之重量比為100：1)、PT-A(5%)軟膏處理組以及丙酸氯氟美松(0.05%)軟膏處理組)之小鼠之發紅、脫屑及皮膚厚度的嚴重程度評分。 Figure 8C shows the control group (vehicle) and the five experimental groups (floxacin (0.05%; Intermediate steroid) ointment treatment group, fluocinolone + PT-A (0.25%) ointment treatment group (PT-A to fluocinolone weight ratio is 5: 1), fluocinolone + PT-A (5%) ointment treatment group Redness and desquamation in mice (weight ratio of PT-A to fluocinolone of 100: 1), PT-A (5%) ointment treatment group and cloflomethasone propionate (0.05%) ointment treatment group) And skin thickness severity scores.

第9A圖顯示，控制組(媒劑)以及三個實驗組(PT-A(含量25mg/g)軟膏處理組、可立舒乳膏(CLOBETASOL Cream，混合乳膏基劑丙酸氯氟美松含量為0.25mg/g)處理組以及妥膚淨親水軟膏(TOPSYM Cream，混合乳膏基劑氟輕松含量為0.25mg/g)處理組)之小鼠的耳朵厚度。 Figure 9A shows the control group (vehicle) and the three experimental groups (PT-A (content 25mg / g) ointment treatment group, CLOBETASOL Cream, mixed cream base clofomethasone propionate Ear thickness of mice in the treatment group (content: 0.25 mg / g) and the treatment group (TOPSYM Cream, mixed cream base with fluocinolone content of 0.25 mg / g).

第9B圖顯示，控制組(媒劑)以及三個實驗組(PT-A(含量25mg/g)軟膏處理組、可立舒乳膏(CLOBETASOL Cream，混合乳膏基劑丙酸氯氟美松含量為0.25mg/g)處理組與妥膚淨親水軟膏(TOPSYM Cream，混合乳膏基劑氟輕松含量為0.25mg/g)處理組)之小鼠的皮膚樣本的蘇木素-伊紅染色結果。 Figure 9B shows the control group (vehicle) and the three experimental groups (PT-A (content 25mg / g) ointment treatment group, CLOBETASOL Cream, mixed cream base clofomethasone propionate Hematoxylin-eosin staining results of skin samples from mice treated with TOPSYM Cream (TOPSYM Cream, mixed cream base with fluocinolone content of 0.25 mg / g) treated mice).

第10A圖顯示，控制組(媒劑)、對照組(Clobetasol)及兩組實驗組(PT-A(含量25mg/g)軟膏處理組與PT-A(含量25mg/g)混合可立舒乳膏(CLOBETASOL Cream含量0.25mg/g)(Clobetasol+PT-A)之軟膏處理組)之小鼠的耳朵厚度。 Figure 10A shows that the control group (vehicle), the control group (Clobetasol), and the two experimental groups (PT-A (content 25mg / g) ointment-treated group and PT-A (content 25mg / g) mixed with cresyl milk Ear thickness of mice with a cream (CLOBETASOL Cream content of 0.25 mg / g) (Clobetasol + PT-A) ointment treatment group).

第10B圖顯示，控制組(媒劑)、對照組(Clobetasol)及兩組實驗組(PT-A(含量25mg/g)軟膏處理組與PT-A(含量25mg/g)混合可立舒乳膏(CLOBETASOL Cream含量0.25mg/g) (Clobetasol+PT-A)之軟膏處理組)之小鼠的皮膚樣本的蘇木素-伊紅染色結果。 Figure 10B shows that the control group (vehicle), the control group (Clobetasol), and the two experimental groups (PT-A (content 25mg / g) ointment-treated group and PT-A (content 25mg / g) mixed with cresol milk Cream (CLOBETASOL Cream 0.25mg / g) (Clobetasol + PT-A) ointment-treated group) The results of hematoxylin-eosin staining on skin samples of mice.

第11A圖顯示，控制組(未經任何處理)、對照組(Rinderon-V(0.06%)軟膏處理組)及實驗組(PT-A(含量25mg/g)軟膏處理組之小鼠的皮膚外觀。 Figure 11A shows the skin appearance of mice in the control group (without any treatment), the control group (Rinderon-V (0.06%) ointment treatment group) and the experimental group (PT-A (content 25mg / g) ointment treatment group). .

第11B圖顯示，控制組(未經任何處理)、對照組(Rinderon-V(0.06%)軟膏處理組)及實驗組(PT-A(含量25mg/g)軟膏處理組)之小鼠皮膚樣本的蘇木素-伊紅染色結果。 Figure 11B shows mouse skin samples from the control group (without any treatment), the control group (Rinderon-V (0.06%) ointment treatment group), and the experimental group (PT-A (content 25mg / g) ointment treatment group). Hematoxylin-eosin staining results.

第12圖顯示，PT-A(含量25mg/g)軟膏處理之人類皮膚重覆刺激性與過敏性試驗結果。於人種欄中，C代表高加索人(Caucasian)，H代表拉丁美洲人(Hispanic)；於反應欄位中，Dc(Discontinued)意指受試者缺席無法測試；於分數欄位中，N/A(Not applicable)代表由於受試者缺席致分數無法計算。 Figure 12 shows the results of repeated irritation and allergy tests on human skin treated with PT-A (content 25mg / g) ointment. In the ethnographic column, C stands for Caucasian, H stands for Latino (Hispanic); in the response field, Dc (Discontinued) means that the subject cannot be tested in absence; in the score field, N / A (Not applicable) means the score cannot be calculated due to the absence of the subject.

在本發明一實施態樣中，提供一種中草藥萃取物用於製備治療皮膚疾病之藥物的用途。 In one aspect of the present invention, a Chinese herbal medicine extract is provided for use in preparing a medicament for treating skin diseases.

上述皮膚疾病可包括自體免疫相關皮膚疾病或感染性皮膚疾病。而上述自體免疫相關皮膚疾病的例子，可包括，但不限於乾癬、過敏性皮膚炎、異位性皮膚炎等。 The aforementioned skin diseases may include autoimmune-related skin diseases or infectious skin diseases. Examples of the above-mentioned autoimmune-related skin diseases may include, but are not limited to, psoriasis, allergic dermatitis, and atopic dermatitis.

於本發明之中草藥萃取物用於製備治療皮膚疾病之藥物的用途中，上述中草藥萃取物的一製備原料可包括甘草、柴胡、黃芩、五味子與芍藥。在一實施例中，上述中草藥萃取物的 一製備原料係由甘草、柴胡、黃芩、五味子與芍藥所組成。 In the use of the Chinese herbal medicine extract of the present invention for preparing a medicine for treating skin diseases, a raw material for preparing the Chinese herbal medicine extract may include licorice, Bupleurum, Scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora. In one embodiment, the A preparation raw material is composed of licorice, bupleurum, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora.

上述甘草的例子可包括生甘草、炙甘草等，但不限於此。而上述柴胡則可包括，但不限於，生北柴胡、高氏柴胡等。上述黃芩可包括例如枯黃芩、條黃芩等，但不限於此。又，上述五味子的例子則可包括，但不限於，北五味子、南五味子等。此外，上述芍藥則可包括，但不限於赤芍、白芍、牡丹等。 Examples of the foregoing licorice may include raw licorice, licorice, etc., but are not limited thereto. The aforementioned Bupleurum may include, but is not limited to, raw North Bupleurum, Gao's Bupleurum and the like. The Scutellaria baicalensis may include, for example, Scutellaria baicalensis, Scutellaria baicalensis, etc., but is not limited thereto. In addition, examples of the above-mentioned schisandra may include, but are not limited to, north schisandra and south schisandra. In addition, the aforementioned peony medicine may include, but is not limited to, red peony, white peony, peony and the like.

又於上述中草藥萃取物的製備原料中，甘草、柴胡、黃芩、五味子與芍藥的重量比可為約1-5：1-5：1-5：1-5：1-5，但不限於此。在一實施例中，於上述中草藥萃取物的製備原料中，甘草、柴胡、黃芩、五味子與芍藥的重量比可為約1：1：1：1：1。 In the preparation materials of the Chinese herbal medicine extract, the weight ratio of licorice root, bupleurum root, scutellaria baicalensis, schisandra and paeonia lactiflora may be about 1-5: 1-5: 1-5: 1-5: 1-5, but is not limited to this. In one embodiment, in the raw materials for preparing the Chinese herbal medicine extract, the weight ratio of licorice root, bupleurum root, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora may be about 1: 1: 1: 1: 1: 1.

而獲得上述中草藥萃取物之方式並無特別限制，可以目前本技術領域所知之各種方式來獲得。在一實施例中，可藉由包括以下步驟之一萃取方法所獲得：首先將前述製備原料中之甘草、柴胡、黃芩、五味子與芍藥混合以形成一原料混合物，然後，將原料混合物以一溶劑進行一萃取製程。在另一實施例中，則可藉由包括以下步驟之另一萃取方法所獲得：首先將上述製備原料中之甘草、柴胡、黃芩、五味子與芍藥分別以一溶劑進行萃取以產生一甘草萃取物、一柴胡萃取物、一黃芩萃取物、一五味子萃取物與一芍藥萃取物，接著，將上述甘草萃取物、柴胡萃取物、黃芩萃取物、五味子萃取物與芍藥萃取物進行混合。 The method for obtaining the Chinese herbal medicine extract is not particularly limited, and can be obtained by various methods known in the art. In an embodiment, it can be obtained by an extraction method including one of the following steps: firstly mixing licorice root, bupleurum, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora in the aforementioned preparation raw materials to form a raw material mixture; The solvent is subjected to an extraction process. In another embodiment, it can be obtained by another extraction method including the following steps: firstly extracting licorice root, bupleurum root, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora in the above preparation raw materials with a solvent to produce a licorice extract Extract, a Bupleurum extract, a Scutellaria baicalensis extract, a Schisandra chinensis extract, and a Paeonia lactiflora extract. Next, the above-mentioned licorice extract, Bupleurum extract, Scutellaria baicalensis extract, Schisandra chinensis extract and Paeonia lactiflora extract are mixed.

而上述用以進行萃取製程之溶劑可包括水或一有機溶劑，但不限於此。上述之有機溶劑可包括，但不限於醇類、酮類、酸類、酯類等。又，上述醇類的例子可包括甲醇、乙醇等，但不限於此。在一實施例中，上述溶劑可為乙醇。在一特定實施 例中，上述溶劑可為30%乙醇。在另一特定實施例中，上述溶劑可為75%乙醇。 The solvent used for the extraction process may include water or an organic solvent, but is not limited thereto. The above organic solvents may include, but are not limited to, alcohols, ketones, acids, esters, and the like. Examples of the alcohols include, but are not limited to, methanol and ethanol. In one embodiment, the solvent may be ethanol. In a specific implementation In an example, the solvent may be 30% ethanol. In another specific embodiment, the solvent may be 75% ethanol.

在一實施例中，於上述中草藥萃取物的一製備原料中，甘草為生甘草、柴胡為北柴胡、黃芩為枯黃芩、五味子為北五味子且芍藥為赤芍。上述生甘草、北柴胡、枯黃芩、北五味子與赤芍的重量比可為約1：1：1：1：1，但不限於此。又，於一特定實施例中，上述中草藥萃取物的一製備原料包括生甘草、北柴胡、枯黃芩、北五味子與赤芍，而生甘草、北柴胡、枯黃芩、北五味子與赤芍的重量比可為約1：1：1：1：1，且上述中草藥萃取物係藉由包括以下步驟之一萃取方法所獲得：將製備原料中之該生甘草、該北柴胡、該枯黃芩、該北五味子與該赤芍混合以形成一原料混合物，之後將原料混合物以一溶劑進行一萃取製程。又於此特定實施例中，所述用以進行萃取製程之溶劑可為乙醇，例如30%乙醇、75%乙醇等。 In one embodiment, in a preparation raw material of the Chinese herbal medicine extract, licorice is raw licorice, Bupleurum is Bei Chaihu, Scutellaria baicalensis is Scutellaria baicalensis, Schisandra chinensis is Schisandra chinensis and paeonia lactiflora is red peony. The weight ratio of the raw licorice, Bupleurum grandiflora, Scutellaria baicalensis, Schisandra chinensis and red scallion may be about 1: 1, but is not limited thereto. Also, in a specific embodiment, a raw material for the preparation of the Chinese herbal medicine extract includes raw licorice, bei chaihu, scutellaria baicalensis, schisandra chinensis, and red scallion, and raw licorice, bei haihu, scutellaria baicalensis, schisandra chinensis, and scallion The weight ratio can be about 1: 1: 1: 1: 1, and the Chinese herbal medicine extract is obtained by an extraction method including one of the following steps: the raw licorice root, the beihaihu, the dried Scutellaria baicalensis, the Schisandra chinensis and the red scallion are mixed to form a raw material mixture, and then the raw material mixture is subjected to an extraction process with a solvent. In this specific embodiment, the solvent used for the extraction process may be ethanol, such as 30% ethanol, 75% ethanol, and the like.

於上述本發明之中草藥萃取物用於製備治療皮膚疾病之藥物的用途中，所製備之治療皮膚疾病的藥物可為局部給藥劑型或全身給藥劑型，但不限於此。在一實施例中，所製備之治療皮膚疾病的藥物為局部給藥劑型，且此局部給藥劑型的例子可包括，但不限於軟膏、乳劑、液劑、凝膠等。 In the use of the Chinese herbal medicine extract of the present invention for the preparation of a medicament for treating skin diseases, the medicament for treating the skin diseases may be a local administration form or a systemic administration form, but is not limited thereto. In one embodiment, the prepared medicine for treating skin diseases is a topical dosage form, and examples of the topical dosage form may include, but are not limited to, ointments, emulsions, liquids, gels, and the like.

以上述任一種中草藥萃取物所製備出之治療皮膚疾病的藥物，具有高度之安全性，且不會對個體產生不良作用。又，以上述任一種中草藥萃取物所製備出之治療皮膚疾病的藥物，對於治療各種皮膚疾病，具有優良的功效，特別是對於具有發炎症狀之皮膚疾病，具有優異之減緩發炎效果。 The medicine for treating skin diseases prepared by using any of the above Chinese herbal medicine extracts is highly safe and does not cause adverse effects on individuals. In addition, the medicine for treating skin diseases prepared by using any of the Chinese herbal medicine extracts described above has excellent efficacy in treating various skin diseases, especially for skin diseases with inflammation symptoms, and has an excellent anti-inflammatory effect.

在另一實施例中，對於上述本發明之中草藥萃取物用於製備治療皮膚疾病之藥物的用途而言，可更包括將前述任一中草藥萃取物與一類固醇一起用於製備治療皮膚疾病之藥物的用途。於此實施例中，中草藥萃取物與類固醇之重量比可為約5：1-200：1，但不限於此。在一特定實施例中，中草藥萃取物與類固醇之重量比可為約83：1。而在另一特定實施例中，中草藥萃取物與類固醇之重量比可為約5：1。而在又另一特定實施例中，中草藥萃取物與類固醇之重量比可為約100：1。 In another embodiment, for the use of the herbal extract of the present invention for preparing a drug for treating skin diseases, the method may further include using any one of the foregoing Chinese herbal extracts with a steroid to prepare a drug for treating skin diseases. the use of. In this embodiment, the weight ratio of the Chinese herbal medicine extract to the steroid may be about 5: 1-200: 1, but is not limited thereto. In a specific embodiment, the weight ratio of the Chinese herbal medicine extract to the steroid may be about 83: 1. In another specific embodiment, the weight ratio of the Chinese herbal medicine extract to the steroid may be about 5: 1. In yet another specific embodiment, the weight ratio of the Chinese herbal medicine extract to the steroid may be about 100: 1.

而上述類固醇可為任何適合用於皮膚治療的類固醇，例如可***(dexamethasone)、氟米(fluorometholone)、甲羥松(medrysone)、倍他米松(betamethasone)、曲安西龍(triamcinolone)、潑尼松(prednisone)、潑尼松龍(prednisolone)、氫化可的松(hydrocortisone)等，但不限於此。 The steroid may be any steroid suitable for skin treatment, such as dexamethasone, fluorometholone, medrysone, betamethasone, triamcinolone, Prednisone, prednisolone, hydrocortisone, and the like are not limited thereto.

又，於上述將前述任一中草藥萃取物與一類固醇一起用於製備治療皮膚疾病之藥物的用途的實施例中，所製備之治療皮膚疾病的藥物也同樣可為局部給藥劑型或全身給藥劑型，但不限於此。在一特定實施例中，所製備之治療皮膚疾病的藥物為局部給藥劑型，且此局部給藥劑型的例子可包括，但不限於軟膏、乳劑、液劑、凝膠等。 Moreover, in the above-mentioned embodiment of the use of any one of the foregoing Chinese herbal medicine extracts together with a steroid to prepare a medicine for treating skin diseases, the medicine for treating skin diseases prepared may also be a local administration form or a systemic administration agent. Type, but not limited to this. In a specific embodiment, the prepared medicine for treating skin diseases is a topical dosage form, and examples of the topical dosage form may include, but are not limited to, ointments, emulsions, liquids, gels, and the like.

由上述任一種中草藥萃取物搭配類固醇所製備出之治療皮膚疾病的藥物，對於治療各種皮膚疾病，具有優良的功效，特別是對於具有發炎症狀之皮膚疾病，具有優異之減緩發炎效果。又，於此藥物中，中藥萃取物可具有降低所搭配之類固醇所產生的副作用的功效，及/或相較於單獨使用此類固醇時所需之有 效劑量，藉由搭配中藥萃取物此類固醇所需有效劑量得以降低。 The medicine for treating skin diseases prepared from any of the Chinese herbal medicine extracts and steroids has excellent efficacy for treating various skin diseases, especially for skin diseases with inflammation symptoms, and has excellent anti-inflammatory effects. In addition, in this medicine, Chinese herbal extracts can have the effect of reducing the side effects of the steroids used, and / or compared with those required when using such steroids alone The effective dose can be reduced by matching with the traditional Chinese medicine extract such steroids.

在本發明另一實施態樣中，提供一種中草藥萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途。 In another aspect of the present invention, a Chinese herbal medicine extract is provided for use in the preparation of a medicament for improving the side effects of steroid treatment of skin diseases.

上述類固醇可為任何適合用於皮膚治療的類固醇。而適合用於皮膚治療的類固醇的例子則可包括，但不限於可***、氟米、甲羥松、倍他米松、曲安西龍、潑尼松、潑尼松龍、氫化可的松等。 The aforementioned steroid may be any steroid suitable for use in skin treatment. Examples of steroids suitable for skin treatment may include, but are not limited to, dexamethasone, flumizone, methasone, betamethasone, triamcinolone, prednisone, prednisone, hydrocortisone Wait.

而上述皮膚疾病可包括自體免疫相關皮膚疾病或感染性皮膚疾病。而上述自體免疫相關皮膚疾病的例子，可包括，但不限於乾癬、過敏性皮膚炎、異位性皮膚炎等。 The aforementioned skin diseases may include autoimmune-related skin diseases or infectious skin diseases. Examples of the above-mentioned autoimmune-related skin diseases may include, but are not limited to, psoriasis, allergic dermatitis, and atopic dermatitis.

又，上述以類固醇治療皮膚疾病之副作用意指，以類固醇治療皮膚疾病時所可能引發之任何不良情況或狀態，例如皮膚變薄及/或血管擴張等，但不限於此。 In addition, the above-mentioned side effect of treating skin diseases with steroids means any adverse condition or condition that may be caused when treating skin diseases with steroids, such as skin thinning and / or vasodilation, but is not limited thereto.

又，對於本發明中草藥萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途而言，於此所述之中草藥萃取物可為前方中草藥萃取物用於製備治療皮膚疾病之藥物的用途之相關段落中所提及的任一種中草藥萃取物，故不再於此重複贅述。 In addition, for the use of the Chinese herbal medicine extract of the present invention for preparing a medicament for improving the side effects of steroids for treating skin diseases, the Chinese herbal medicine extract described herein can be the use of the front Chinese herbal medicine extract for preparing a medicine for treating skin diseases Any of the Chinese herbal extracts mentioned in the relevant paragraphs will not be repeated here.

此外，於上述本發明之中草藥萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途中，所製備之藥物可為局部給藥劑型或全身給藥劑型，但不限於此。在一實施例中，所製備之藥物為局部給藥劑型，且此局部給藥劑型的例子可包括，但不限於軟膏、乳劑、液劑、凝膠等。 In addition, in the use of the herbal extract of the present invention for the preparation of a medicament for improving the side effects of steroids for treating skin diseases, the prepared medicament may be a topical or systemic dosage form, but is not limited thereto. In one embodiment, the prepared medicine is a topical dosage form, and examples of the topical dosage form may include, but are not limited to, ointments, emulsions, liquids, gels, and the like.

在本發明又另一實施態樣中，提供一種減緩皮膚疾 病的醫藥組成物。 In yet another aspect of the present invention, a skin alleviation is provided. Sick medical composition.

上述皮膚疾病可包括自體免疫相關皮膚疾病或感染性皮膚疾病。而上述自體免疫相關皮膚疾病的例子，可包括，但不限於乾癬、過敏性皮膚炎、異位性皮膚炎等。 The aforementioned skin diseases may include autoimmune-related skin diseases or infectious skin diseases. Examples of the above-mentioned autoimmune-related skin diseases may include, but are not limited to, psoriasis, allergic dermatitis, and atopic dermatitis.

本發明減緩皮膚疾病的醫藥組成物可包括，但不限於一中草藥萃取物與一類固醇。 The pharmaceutical composition for reducing skin diseases of the present invention may include, but is not limited to, a Chinese herbal medicine extract and a steroid.

本發明之減緩皮膚疾病的醫藥組成物所包含的中草藥萃取物，可為前方中草藥萃取物用於製備治療皮膚疾病之藥物的用途之相關段落中所提及的任一種中草藥萃取物，故不再於此重複贅述。 The Chinese herbal medicine extract contained in the medicinal composition for slowing skin diseases of the present invention may be any one of the Chinese herbal medicine extracts mentioned in the relevant paragraphs on the use of the previous Chinese herbal medicine extract to prepare a medicine for treating skin diseases, so it is no longer Repeated descriptions are repeated here.

而本發明之減緩皮膚疾病的醫藥組成物所包含的類固醇，則可為任何適合用於皮膚治療的類固醇。適合用於皮膚治療的類固醇的例子可包括，可***、氟米、甲羥松、倍他米松、曲安西龍、潑尼松、潑尼松龍、氫化可的松等，但不限於此。 The steroid contained in the pharmaceutical composition for slowing skin diseases of the present invention may be any steroid suitable for skin treatment. Examples of steroids suitable for use in skin treatment may include, but are not limited to, dexamethasone, flumide, methasone, betamethasone, triamcinolone, prednisone, prednisone, hydrocortisone, and the like this.

於本發明之減緩皮膚疾病的醫藥組成物中，中草藥與類固醇之含量並無特別限制，只要所形成之醫藥組成物具有治療皮膚疾病之功效即可。上述中草藥萃取物與類固醇之重量比可為約5：1-200：1，但不限於此。在一實施例中，中草藥萃取物與類固醇之重量比可為約83：1。在另一實施例中，中草藥萃取物與類固醇之重量比可為約5：1。而在又另一實施例中，中草藥萃取物與類固醇之重量比可為約100：1。 In the medicinal composition for slowing skin diseases of the present invention, the content of Chinese herbal medicine and steroids is not particularly limited, as long as the formed medicinal composition has the effect of treating skin diseases. The weight ratio of the Chinese herbal medicine extract to the steroid may be about 5: 1-200: 1, but is not limited thereto. In one embodiment, the weight ratio of the Chinese herbal extract to the steroid may be about 83: 1. In another embodiment, the weight ratio of the Chinese herbal medicine extract to the steroid may be about 5: 1. In yet another embodiment, the weight ratio of the Chinese herbal extract to the steroid may be about 100: 1.

本發明之減緩皮膚疾病的醫藥組成物可為局部給藥劑型或全身給藥劑型，但不限於此。在一實施例中，本發明之減緩皮膚疾病的醫藥組成物為局部給藥劑型，且此局部給藥劑型的 例子可包括，但不限於軟膏、乳劑、液劑、凝膠等。 The medicinal composition for reducing skin diseases of the present invention may be a local administration form or a systemic administration form, but is not limited thereto. In one embodiment, the pharmaceutical composition for slowing skin diseases of the present invention is a topical dosage form, and the topical dosage form Examples may include, but are not limited to, ointments, creams, liquids, gels, and the like.

在另一實施例中，上述本發明之減緩皮膚疾病的醫藥組成物可更包括一藥學上可接受之媒劑、載體或鹽類。 In another embodiment, the pharmaceutical composition for reducing skin diseases of the present invention may further include a pharmaceutically acceptable vehicle, carrier, or salt.

藥學上可接受之媒劑可做為活性成分之稀釋劑、分散劑或載體。藥學上可接受之媒劑可包括常在皮膚護理產品中使用的材料，如水、液體或固體軟化劑、矽酮油、乳化劑、溶劑、濕潤劑、增稠劑、粉末、噴射劑與類似物。 A pharmaceutically acceptable vehicle can be used as a diluent, dispersant or carrier for the active ingredient. Pharmaceutically acceptable vehicles can include materials commonly used in skin care products, such as water, liquid or solid softeners, silicone oils, emulsifiers, solvents, wetting agents, thickeners, powders, sprays and the like .

媒劑可佔上述組合物之80-99.9wt%，較佳為85-95wt%，並可以在沒有其它佐劑的存在下構成組合物的其餘部份。 The vehicle may account for 80-99.9 wt%, preferably 85-95 wt% of the above composition, and may constitute the remainder of the composition in the absence of other adjuvants.

又，前述組合物也可更包括其它特殊的皮膚受益活化物，如防曬劑及皮膚淡化劑。媒劑也可以進一步包括如抗氧化劑、香料、遮光劑、防腐劑、著色劑及緩衝液之類的佐劑。 In addition, the aforementioned composition may further include other special skin benefit activating agents, such as sunscreen agents and skin lightening agents. The vehicle may further include adjuvants such as antioxidants, perfumes, sunscreens, preservatives, colorants, and buffers.

此外，前述之所有組合物於一實施例中皆可製作成一皮膚塗劑型式包括，但不限於，乳劑、膏劑、凝膠、噴劑、化妝水、洗髮水或幕斯等。一般來說，皮膚噴劑可由噴霧狀共聚物所組成，例如，聚乙烯吡咯烷酮、醋酸乙烯及其類似物，且其可具有化妝水之功能。皮膚凝膠的製備方法與噴劑類似，但其為凝膠狀且無乙醇的存在，可附著於皮膚上。皮膚幕斯為利用壓力釋放泡沫。皮膚乳劑為一疏水性或親水性乳劑、膏劑、凝膠、潤膚劑、噴劑、塗劑、皮膚調理水、洗髮水或幕斯。另外，更可添加適合的成份至皮膚乳劑，此額外添加的成份包括凡士林、蠟、羊毛脂、矽、微脂體、蔬菜、礦物油、增塑劑、香料、防腐劑、促滲透劑、pH值調整劑或其他適合用於局部皮膚的成份。此額外的成份可濕潤皮膚，穩定活性化合物，增加前述組合物-皮膚的接 觸，局部區域的濃度，控制組合物的釋放。 In addition, all the aforementioned compositions can be made into a skin lotion in one embodiment, including, but not limited to, emulsions, creams, gels, sprays, lotions, shampoos, or moses. Generally, skin sprays may be composed of a spray-like copolymer, such as polyvinylpyrrolidone, vinyl acetate, and the like, and they may have the function of a lotion. The preparation method of skin gel is similar to spray, but it is gel-like and free of ethanol, and can be attached to the skin. Skin Moss uses pressure to release foam. The skin emulsion is a hydrophobic or hydrophilic emulsion, ointment, gel, emollient, spray, lotion, skin conditioning water, shampoo or mousse. In addition, suitable ingredients can be added to the skin emulsion. The additional ingredients include petrolatum, wax, lanolin, silicon, microlipids, vegetables, mineral oils, plasticizers, spices, preservatives, penetration enhancers, pH Value modifiers or other ingredients suitable for topical skin. This additional ingredient moisturizes the skin, stabilizes the active compound, and increases the aforementioned composition-to-skin connection Touch, the concentration of the local area, to control the release of the composition.

前述藥學上可接受之載體可包括，但不限於溶劑、分散媒(dispersion medium)、套膜(coating)、抗菌與抗真菌試劑與一等滲透壓與吸收延遲(absorption delaying)試劑等與藥學投予相容者。對於不同的給藥方式，可利用一般方法將藥學組合物配置成劑型(dosage form)。 The aforementioned pharmaceutically acceptable carriers may include, but are not limited to, solvents, dispersion media, coatings, antibacterial and antifungal agents, and first-class osmotic pressure and absorption delaying agents, etc. To compatible. For different modes of administration, general methods can be used to configure the pharmaceutical composition into a dosage form.

又，上述藥學上可接受之鹽類可包括，但不限於鹽類包括無機陽離子，例如，鹼金屬鹽類，如鈉、鉀或胺鹽，鹼土金族鹽類，如鎂、鈣鹽，含二價或四價陽離子之鹽類，如鋅、鋁或鋯鹽。此外，也可是為有機鹽類，如二環己胺鹽類、甲基-D-葡糖胺，胺基酸鹽類，如精胺酸、離胺酸、組織胺酸、麩胺酸醯胺。 In addition, the above pharmaceutically acceptable salts may include, but are not limited to, salts including inorganic cations, for example, alkali metal salts such as sodium, potassium or amine salts, alkaline earth gold salts such as magnesium and calcium salts, containing Divalent or tetravalent cation salts, such as zinc, aluminum or zirconium salts. In addition, it can also be organic salts, such as dicyclohexylamine salts, methyl-D-glucosamine, amino acid salts, such as arginine, lysine, histamine, and glutamine. .

本發明醫藥組成物給藥可以非口服、口服、經由吸入噴霧(inhalation spray)或藉由植入貯存器(implanted reservoir)的方式。非口服可包括塗擦患部、皮下(subcutaneous)、皮內(intracutaneous)靜脈內(intravenous)、肌肉內(intramuscular)、關節內(intraarticular)動脈(intraarterial)、滑囊(腔)內(intrasynovial)、胸骨內(intrasternal)蜘蛛膜下腔(intrathecal)、疾病部位內(intralesional)注射以及灌注技術。 The pharmaceutical composition of the present invention can be administered parenterally, orally, via an inhalation spray, or by an implanted reservoir. Parenteral administration may include rubbing the affected area, subcutaneous, intracutaneous intravenous, intramuscular, intraarticular intraarterial, intrasynovial, sternum Intrasternal intrathecal, intralesional injection and perfusion techniques.

塗擦之局部用藥成分的形式可包括軟膏、乳劑、液劑、凝膠等，但不限於此。 The form of rubbing topical ingredients may include, but is not limited to, ointments, creams, liquids, gels, and the like.

口服成分的形式可包括，但不限定於，藥錠、膠囊、乳劑(emulsions)、水性懸浮液(aqueous suspensions)、分散液(dispersions)與溶液。 The form of the oral ingredient may include, but is not limited to, tablets, capsules, emulsions, aqueous suspensions, dispersions, and solutions.

上述本發明之任一種減緩皮膚疾病的醫藥組成物，對於減緩各種皮膚疾病，皆具有優良的功效，特別是對於具有發炎症狀之皮膚疾病，具有優異之減緩及/或治療皮膚發炎效果。又，於此醫藥組成物中，中藥萃取物可具有降低所搭配之類固醇所產生的副作用的功效，及/或相較於單獨使用此類固醇時所需之有效劑量，藉由搭配中藥萃取物此類固醇所需有效劑量得以降低。 Any of the pharmaceutical compositions for slowing skin diseases of the present invention described above has excellent effects for slowing various skin diseases, especially for skin diseases with inflammation symptoms, and has excellent slowing and / or treating skin inflammation effects. In addition, in this medicinal composition, the traditional Chinese medicine extract can have the effect of reducing the side effects produced by the steroids used, and / or compared with the effective dose required when such steroids are used alone, The effective dose required for steroids is reduced.

實施例 Examples

A.各種試驗萃取物之製備 A. Preparation of various test extracts

1.外用軟膏劑型 1. Ointment for external use

(1)藉由30%乙醇溶液萃取之枯黃芩、北柴胡、生甘草、赤芍及北五味子複方藥材萃取物、黃芩單方萃取物、柴胡單方萃取物以及黃芩及柴胡複方藥材萃取物 (1) Withered 30% ethanol solution of Scutellaria baicalensis, Bei Chaihu, raw licorice, Radix scutellariae and Schisandra chinensis compound medicinal material extract, Scutellaria baicalensis extract, Bupleurum single extract, and Scutellaria baicalensis and Bupleurum compound extract

將以下四種不同複方及單方的中草藥配方(1)黃芩、北柴胡、甘草、芍藥及北五味子複方藥材(重量比1：1：1：1：1)(PT-A)、(2)黃芩單方(SR)、(3)柴胡單方(BR)以及(4)黃芩及柴胡複方藥材(重量比1：1)(SR+BR)，分別進行下述萃取程序： The following four different compound and unilateral Chinese herbal medicine formulas are: Scutellaria baicalensis (SR), (3) Bupleurum single (BR), and (4) Scutellaria baicalensis and Bupleurum compound herbs (weight ratio 1: 1) (SR + BR) were subjected to the following extraction procedures:

將中草藥配方以10倍重量之30%乙醇溶液加熱萃取1小時，以獲得一第一萃取液。將第一萃取液取出，再將經萃取之前述配方同樣以10倍重量之30%乙醇溶液再加熱萃取1小時，以獲得第二次萃取液。然後，將兩次萃取液混合。將所得之萃取液以100mesh篩網進行過濾，再經減壓濃縮，之後進行冷凍乾燥。 The Chinese herbal medicine formula is heated and extracted with 10% weight 30% ethanol solution for 1 hour to obtain a first extract. The first extraction liquid is taken out, and the previously extracted formula is similarly heated and extracted with a 30% ethanol solution of 10 times the weight for another hour to obtain a second extraction liquid. Then, the two extracts were mixed. The obtained extract was filtered through a 100 mesh sieve, concentrated under reduced pressure, and then freeze-dried.

將中草藥配方冷凍乾燥粉末(1g)與95%酒精(1.4g)、聚乙二醇400(10g)、聚乙二醇4000(4.5g)、和聚氧乙烯氫化蓖麻油(0.15g)，及高純度的去離子水(deionized water)(2.95ml) 加熱至60℃並混合到均勻，以製作成外用軟膏劑型。 Freeze-dried powder of Chinese herbal medicine (1g) with 95% alcohol (1.4g), polyethylene glycol 400 (10g), polyethylene glycol 4000 (4.5g), and polyoxyethylene hydrogenated castor oil (0.15g), and High-purity deionized water (2.95ml) Heat to 60 ° C and mix until homogeneous to make an ointment for external use.

即，獲得以下所列四種軟膏：(1)黃芩、北柴胡、甘草、芍藥及北五味子複方藥材(重量比1：1：1：1：1)(PT-A)之軟膏、(2)黃芩單方(SR)之軟膏、(3)柴胡單方(BR)之軟膏以及(4)黃芩及柴胡複方藥材(重量比1：1)(SR+BR)之軟膏。 That is, four ointments listed below were obtained: (1) ointment of Scutellaria baicalensis, Bei Chaihu, licorice, paeonia lactiflora and compound Schisandra chinensis (weight ratio 1: 1: 1: 1: 1: 1) (PT-A), (2 ) Ointment of Scutellaria baicalensis (SR), (3) Ointment of scutellaria chinensis (BR) and (4) Ointment of Scutellaria baicalensis and Bupleurum compound (weight ratio 1: 1) (SR + BR)

(2)藉由30%乙醇溶液分別萃取各單方藥材並將各單方萃取物混合所獲得之混合萃取物 (2) A mixed extract obtained by extracting each unilateral medicinal material separately by 30% ethanol solution and mixing each unilateral extract

將以下五種不同單方中草藥，黃芩、北柴胡、甘草、芍藥、北五味子單方分別進行以下萃取製程： The following five different unilateral Chinese herbal medicines, Scutellaria baicalensis, Bei Chaihu, licorice, Paeonia lactiflora, and Schisandra chinensis were subjected to the following extraction processes:

將單一中草藥以10倍重量之30%乙醇溶液加熱萃取1小時，以獲得一第一萃取液。將第一萃取液取出，再將經萃取之前述配方同樣以10倍重量之30%乙醇溶液再加熱萃取1小時，以獲得第二次萃取液。然後，將兩次萃取液混合。將所得之萃取液以100mesh篩網進行過濾。 A single Chinese herbal medicine is heated and extracted with a 30% ethanol solution of 10 times the weight for 1 hour to obtain a first extract. The first extraction liquid is taken out, and the previously extracted formula is similarly heated and extracted with a 30% ethanol solution of 10 times the weight for another hour to obtain a second extraction liquid. Then, the two extracts were mixed. The obtained extract was filtered through a 100 mesh sieve.

即，分別獲得黃芩單方、北柴胡單方、甘草單方、芍藥單方、北五味子單方之濾液。 That is, the filtrates of Scutellaria baicalensis S. unicorne, B. Chaihu S. unicorne, Glycyrrhiza serrata unis.

混合前述五種濾液，以獲得黃芩、北柴胡、甘草單方、芍藥與北五味子之混合濾液(PT-A-1)，再將其經減壓濃縮，之後進行冷凍乾燥。 The aforementioned five kinds of filtrates were mixed to obtain a mixed filtrate (PT-A-1) of Scutellaria baicalensis, Bei Chaihu, Licorice Unicorn, Paeonia lactiflora and Schisandra chinensis, and then concentrated under reduced pressure, followed by freeze-drying.

冷凍乾燥粉末(1g)與95%酒精(1.4g)、聚乙二醇400(10g)、聚乙二醇4000(4.5g)、和聚氧乙烯氫化蓖麻油(0.15克)，及高純度的去離子水(2.95ml)加熱至60℃混合到均勻，製作成軟膏劑型。 Freeze-dried powder (1g) with 95% alcohol (1.4g), polyethylene glycol 400 (10g), polyethylene glycol 4000 (4.5g), and polyoxyethylene hydrogenated castor oil (0.15g), and high purity Deionized water (2.95ml) was heated to 60 ° C and mixed to make an ointment.

即，獲得30%乙醇萃取之黃芩、北柴胡、甘草、芍藥 及北五味子之萃取液混合物(PT-A-1)之軟膏。 That is, Scutellaria baicalensis, Bupleurum chinensis, Licorice, Paeonia lactiflora extracted with 30% ethanol And ointment of Kita schisandra extract mixture (PT-A-1).

(3)藉由75%乙醇溶液萃取之黃芩、北柴胡、甘草、芍藥及北五味子複方藥材萃取物 (3) Extract of Scutellaria baicalensis, Bei Chaihu, licorice, Paeonia lactiflora and Schisandra chinensis compound medicine extracted with 75% ethanol solution

將黃芩、北柴胡、甘草、芍藥及北五味子複方以10倍重量之75%乙醇溶液加熱萃取1小時，以獲得一第一萃取液。將第一萃取液取出，再將經萃取之前述配方同樣以10倍重量之75%乙醇溶液再加熱萃取1小時，以獲得第二次萃取液。然後，將兩次萃取液混合。將所得之萃取液以100mesh篩網進行過濾，再經減壓濃縮，之後進行冷凍乾燥。 The Scutellaria baicalensis, Bei Chai Hu, licorice, Paeonia lactiflora and Schisandra chinensis compound are heated and extracted with a 75% ethanol solution of 10 times the weight for 1 hour to obtain a first extract. The first extraction liquid is taken out, and the previously extracted formula is also heated and extracted with a 75% ethanol solution of 10 times the weight for another hour to obtain a second extraction liquid. Then, the two extracts were mixed. The obtained extract was filtered through a 100 mesh sieve, concentrated under reduced pressure, and then freeze-dried.

將冷凍乾燥粉末(1g)與95%酒精(1.4g)、聚乙二醇400(10g)、聚乙二醇4000(4.5g)、和聚氧乙烯氫化蓖麻油(0.15g)，及高純度的去離子水(2.95ml)加熱至60℃並混合到均勻，以製作成外用軟膏劑型。 Freeze-dried powder (1g) with 95% alcohol (1.4g), polyethylene glycol 400 (10g), polyethylene glycol 4000 (4.5g), and polyoxyethylene hydrogenated castor oil (0.15g), and high purity The deionized water (2.95 ml) was heated to 60 ° C. and mixed until homogeneous to make an ointment for external use.

即，獲得75%乙醇萃取之黃芩、北柴胡、甘草、芍藥及北五味子複方藥材(重量比1：1：1：1：1)(PT-A-2)之軟膏。 That is, an ointment of Scutellaria baicalensis, Bei Chai Hu, licorice root, Paeonia lactiflora and Schisandra chinensis compound medicine (weight ratio 1: 1: 1: 1: 1: 1) (PT-A-2) extracted with 75% ethanol was obtained.

(4)類固醇軟膏 (4) Steroid ointment

將二丙酸倍他米松(Betamethasone dipropionate)粉末(0.006g)、95%酒精(1.4g)、聚乙二醇400(10g)、聚乙二醇4000(4.5g)、和聚氧乙烯氫化蓖麻油(0.15g)，及高純度的去離子(DI)水(3.944ml)加熱至60℃混合到均勻，製作成外用軟膏劑型(BD)。 Betamethasone dipropionate powder (0.006 g), 95% alcohol (1.4 g), polyethylene glycol 400 (10 g), polyethylene glycol 4000 (4.5 g), and polyoxyethylene hydrogenated castor Sesame oil (0.15g) and high-purity deionized (DI) water (3.944ml) were heated to 60 ° C and mixed until homogeneous to prepare an external ointment (BD).

(5)黃芩、北柴胡、甘草、芍藥及北五味子複方藥材與類固醇之混合軟膏 (5) Mixed ointment of Scutellaria baicalensis, Bei Chai Hu, licorice, Paeonia lactiflora and Schisandra chinensis compound medicinal materials and steroids

將PT-A乾燥粉末(0.5g)、二丙酸倍他米松粉末(0.006g)、95%酒精(1.4g)、聚乙二醇400(10g)、聚乙二醇4000(4.5g)、 和聚氧乙烯氫化蓖麻油(0.15g)，及高純度的去離子水(3.444ml)加熱至60℃混合到均勻，製作成外用軟膏劑型(PT-A+BD)。 PT-A dry powder (0.5g), betamethasone dipropionate powder (0.006g), 95% alcohol (1.4g), polyethylene glycol 400 (10g), polyethylene glycol 4000 (4.5g), And polyoxyethylene hydrogenated castor oil (0.15g), and high-purity deionized water (3.444ml) were heated to 60 ° C and mixed to make an external ointment (PT-A + BD).

2.液體劑型 2. Liquid dosage form

將70mg PT-A乾燥粉末以7ml溶劑(10% DMSO與90%三辛酸甘油酯(glyceryl trioctanoate))調配為液體劑型，濃度為10mg/ml。 70 mg of PT-A dry powder was formulated into a liquid dosage form with 7 ml of a solvent (10% DMSO and 90% glyceryl trioctanoate) at a concentration of 10 mg / ml.

B.實驗方法與結果 B. Experimental methods and results

1.實施例1 1. Example 1

複方組合物降低咪喹莫特(imiquimod,IMQ)誘導之類乾癬動物模式皮膚疾病之功效評估 Efficacy of the compound composition in reducing imiquimod (IMQ) -induced skin diseases of animal models of psoriasis

利用咪喹莫特誘導之類乾癬動物模式來評估萃取物對於降低皮膚疾病之影響。其實施步驟如下： Animal models of psoriasis induced by imiquimod were used to evaluate the effect of extracts on reducing skin diseases. The implementation steps are as follows:

首先將Balb/c小鼠(6~8週齡)背部毛髮剃除，並將小鼠分成控制組、對照組與四組實驗組，其中四組實驗組分別為PT-A(100mg)軟膏處理組、SR(100mg)軟膏處理組、BR(100mg)軟膏處理組、SR+BR(100mg)軟膏處理組。 First, shave the back hair of Balb / c mice (6-8 weeks old), and divide the mice into a control group, a control group and four experimental groups, of which the four experimental groups are treated with PT-A (100 mg) ointment. Group, SR (100 mg) ointment treatment group, BR (100 mg) ointment treatment group, SR + BR (100 mg) ointment treatment group.

控制組中未給予小鼠任何處理；對照組則將62.5mg之咪喹莫特乳膏(Aldara；3M Pharmaceuticals)塗抹於小鼠背部，每天給予一次咪喹莫特乳膏，連續給予六天，以誘導小鼠皮膚乾癬症狀產生；而於四組之實驗組中，則先將62.5mg之咪喹莫特乳膏塗抹於小鼠背部，接著對各組分別局部塗抹測試軟膏(100mg)，每天給予一次咪喹莫特乳膏與各實驗組軟膏，連續給予六天。 No treatment was given to the mice in the control group; 62.5 mg of imiquimod cream (Aldara; 3M Pharmaceuticals) was applied to the back of the control group, and imiquimod cream was administered once a day for six consecutive days. In order to induce the symptoms of psoriasis on mice skin, in the experimental group of the four groups, 62.5mg of imiquimod cream was first applied to the back of the mice, and then the test ointment (100mg) was applied topically to each group daily. Imiquimod cream and ointment of each experimental group were given once for six consecutive days.

之後評估動物背部皮膚疾病之程度，包括發紅、脫 屑等項目，並照相。將動物犧牲後，取其背部發炎部位皮膚進行組織的基因表現量檢測，包括IL-17A、IL-6、TNF-α、S100A7等。結果如第1A圖與第1B圖所顯示。 Then assess the extent of skin disease on the back of the animal, including redness, exfoliation Crumbs and other items and photographed. After the animal is sacrificed, the gene expression of the tissues including IL-17A, IL-6, TNF-α, S100A7, etc. is detected on the skin of the back inflammation site. The results are shown in Figures 1A and 1B.

第1A圖顯示，對照組相對於控制組在給予咪喹莫特後，可明顯造成小鼠皮膚發紅與脫屑現象，然而在實驗組中之同時給予咪喹莫特與PT-A後，則可減輕小鼠皮膚疾病現象。但其他三組實驗組並無改善小鼠皮膚疾病現象(第1A圖)。 Figure 1A shows that after the administration of imiquimod to the control group, the skin redness and desquamation of the mice can be significantly caused. However, in the experimental group, imiquimod and PT-A were given at the same time. Can reduce the skin disease phenomenon in mice. But the other three experimental groups did not improve the skin disease phenomenon in mice (Figure 1A).

第1B圖顯示，在基因表現量上，相較於控制組，對照組之IL-17A、IL-6、TNF-α及S100A7均有明顯增加情形，然而於塗抹PT-A軟膏動物之組織，其基因表現量則有下降之趨勢，其中以IL-6、TNF-α及S100A7之表現量與對照組相較下達顯著差異(* p<0.05，***p<0.001)。 Figure 1B shows that in terms of gene expression, compared with the control group, IL-17A, IL-6, TNF-α, and S100A7 in the control group were significantly increased. However, in the tissues of animals coated with PT-A ointment, The gene expression level showed a downward trend. Among them, the expression levels of IL-6, TNF-α and S100A7 were significantly different from those of the control group (* p <0.05, *** p <0.001).

2.實施例2 2.Example 2

複方組合物萃取方式對降低咪喹莫特誘導之類乾癬動物模式皮膚疾病之功效評估 Efficacy evaluation of compound composition extraction method on reducing imiquimod-induced psoriasis in animal models of skin diseases

主要實驗方法與實施例1之相同(並未再設置控制組)，而實驗組則改為PT-A(100mg)軟膏處理組、PT-A-1(100mg)軟膏處理組、PT-A-2(100mg)軟膏處理組的三組實驗組，以評估萃取方式對功效的影響。 The main experimental method is the same as that in Example 1 (the control group is not set), and the experimental group is changed to the PT-A (100mg) ointment treatment group, the PT-A-1 (100mg) ointment treatment group, and PT-A- Two (100 mg) ointment-treated groups were used to evaluate the effect of extraction methods on efficacy.

各實驗組每天給予一次咪喹莫特乳膏及試驗軟膏(100mg)，連續給予六天。 Each experimental group was given imiquimod cream and test ointment (100 mg) once a day for six consecutive days.

之後評估動物背部皮膚疾病之程度，包括發紅、脫屑等項目，且依照脫屑加發紅嚴重程度給予0-8分(最嚴重者給予8分，無症狀者給予0分)並照相。結果如第2A圖與第2B圖所顯示。 The degree of skin disease on the back of the animal was evaluated afterwards, including redness and desquamation, and 0-8 points were given according to the severity of desquamation and redness (8 points in the most severe cases and 0 points in asymptomatic cases) and photographed. The results are shown in Figures 2A and 2B.

依據第2A圖與第2B圖可知，相對於對照組在給予咪喹莫特後之發紅與脫屑現象，實驗組中之同時給予咪喹莫特與100mg PT-A後，可減輕小鼠皮膚疾病現象(第2A圖)，且其改善脫屑情形具有顯著差異(第2B圖)，而PT-A-1與PT-A-2組別無法顯著改善小鼠皮膚疾病情形。 According to Figures 2A and 2B, compared with the control group's redness and desquamation after administration of imiquimod, in the experimental group, simultaneous administration of imiquimod and 100 mg of PT-A can reduce mice. The skin disease phenomenon (Figure 2A), and its improvement in desquamation has a significant difference (Figure 2B), while the PT-A-1 and PT-A-2 groups could not significantly improve the skin disease in mice.

3.實施例3 3. Example 3

腹腔注射PT-A-DS對小鼠類乾癬皮膚疾病之功效評估 Evaluation of the efficacy of intraperitoneal injection of PT-A-DS on psoriasis-like skin diseases in mice

透過咪喹莫特誘導之類乾癬動物模式評估本發明PT-A對於皮膚疾病之影響。其實施步驟如下： The effects of PT-A of the present invention on skin diseases were evaluated by animal models of psoriasis induced by imiquimod. The implementation steps are as follows:

首先將Balb/c小鼠(6~8週齡)背部毛髮剃除，並將小鼠分成控制組、對照組以及實驗組。 First, the hair of Balb / c mice (6-8 weeks old) was shaved, and the mice were divided into control group, control group and experimental group.

控制組中未給予小鼠任何處理；對照組將62.5mg含咪喹莫特乳膏(Aldara；3M Pharmaceuticals)塗抹於小鼠背部，每天給予一次咪喹莫特乳膏，連續給予六天以誘導小鼠皮膚乾癬症狀產生；而實驗組則將62.5mg之咪喹莫特乳膏塗抹於小鼠背部，接著透過腹腔注射給予PT-A-DS(100mg/kg)(溶劑為10% DMSO與90%三辛酸甘油酯(glyceryl trioctanoate))，每天給予一次咪喹莫特乳膏與PT-A-DS(100mg/kg)，連續給予六天。 No treatment was given to the mice in the control group; 62.5 mg of imiquimod cream (Aldara; 3M Pharmaceuticals) was applied to the back of the control group, and imiquimod cream was administered once a day for six consecutive days to induce Symptoms of psoriasis on the skin of mice occurred; while the experimental group applied 62.5mg of imiquimod cream to the back of the mice, and then administered PT-A-DS (100mg / kg) by intraperitoneal injection (solvent: 10% DMSO and 90 % Glyceryl trioctanoate), imiquimod cream and PT-A-DS (100 mg / kg) were administered once a day for six consecutive days.

之後犧牲小鼠，並將其發炎部位皮膚取下浸泡於4%甲醛(formaldehyde)進行固定，接著將樣品以縱切成6μm厚度後，再以蘇木素-伊紅(hematoxylin and eosin)染色，以評估皮膚疾病程度，包括上皮厚度、角化不全或增生等。結果如第3圖所示。 Mice were sacrificed, and the skin at the inflammation site was removed and immersed in 4% formaldehyde for fixation. Then the samples were slit to a thickness of 6 μm, and then stained with hematoxylin and eosin for evaluation. The degree of skin disease, including epithelial thickness, keratosis, or hyperplasia. The results are shown in Figure 3.

第3圖顯示，對照組相對於控制組在給予咪喹莫特 後，可明顯造成小鼠皮膚出現發紅、脫屑及上皮增厚現象，然而，在實驗組中同時給予咪喹莫特與腹腔注射PT-A後，則可減輕小鼠皮膚疾病現象。 Figure 3 shows that the control group was given imiquimod in comparison to the control group. Later, it can obviously cause redness, desquamation, and thickening of epithelium in mice. However, in the experimental group, imiquimod and intraperitoneal injection of PT-A can alleviate the skin disease in mice.

4.實施例4 4.Example 4

PT-A對降低小鼠類乾癬皮膚疾病之功效評估 Evaluation of PT-A on reducing psoriasis-like skin disease in mice

本實施例中，透過咪喹莫特誘導之類乾癬動物模式來評估PT-A軟膏對於皮膚疾病之影響。其實施步驟如下： In this example, the effect of PT-A ointment on skin diseases was evaluated through the animal model of psoriasis induced by imiquimod. The implementation steps are as follows:

首先將Balb/c小鼠(6~8週齡)背部毛髮剃除，並將小鼠分成控制組、對照組以及兩組實驗組，其中兩組實驗組分別為PT-A(10mg)軟膏處理組與PT-A(100mg)軟膏處理組。 First Balb / c mice (6-8 weeks old) were shaved off their back hair, and the mice were divided into control group, control group and two experimental groups, of which the two experimental groups were treated with PT-A (10mg) ointment. The group was treated with PT-A (100 mg) ointment.

控制組中未給予小鼠任何處理；對照組則將62.5mg之咪喹莫特乳膏(Aldara；3M Pharmaceuticals)塗抹於小鼠背部，每天給予一次咪喹莫特乳膏，連續給予六天，以誘導小鼠皮膚乾癬症狀產生；而實驗組則將62.5mg之咪喹莫特乳膏塗抹於小鼠背部，接著局部塗抹PT-A(10mg與100mg)，每天給予一次咪喹莫特乳膏與PT-A軟膏，連續給予六天。 No treatment was given to the mice in the control group; 62.5 mg of imiquimod cream (Aldara; 3M Pharmaceuticals) was applied to the back of the control group, and imiquimod cream was administered once a day for six consecutive days. In order to induce the symptoms of skin psoriasis in mice, the experimental group applied 62.5mg of imiquimod cream to the back of the mice, followed by topical application of PT-A (10mg and 100mg), and gave imiquimod cream once a day. With PT-A ointment, given for six consecutive days.

之後評估動物背部皮膚疾病之程度，包括發紅、脫屑等項目。將動物犧牲後，取其背部發炎部位皮膚進行組織之基因表現量檢測，包括IL-17A、IL-23、IL-22等，並將其發炎部位皮膚取下浸泡於4%甲醛進行固定，接著將樣品以縱切成6μm厚度後，再分別以CD68、CD4、Neutrophil、Ki-67及CD31抗體進行免疫組織染色，以評估皮膚疾病部位之免疫細胞浸潤、細胞增生及血管新生等現象。結果如第4A圖、第4B圖與第4C圖所示。 The degree of skin disease on the back of the animal is then assessed, including items such as redness and desquamation. After the animal is sacrificed, the skin of the back of the inflammation site is taken to detect the gene expression of the tissue, including IL-17A, IL-23, IL-22, etc., and the skin of the inflammation site is removed and immersed in 4% formaldehyde to fix. The samples were cut to a thickness of 6 μm, and then immunohistochemical staining with CD68, CD4, Neutrophil, Ki-67, and CD31 antibodies was performed to evaluate the immune cell infiltration, cell proliferation, and angiogenesis of skin disease sites. The results are shown in Figures 4A, 4B, and 4C.

第4圖顯示，對照組相對於控制組在給予咪喹莫特 後，可明顯造成小鼠背部皮膚增厚現象，然而在實驗組中之同時給予咪喹莫特與100mg PT-A後，則可減輕小鼠皮膚疾病現象。 Figure 4 shows that the control group was given imiquimod in comparison to the control group. Later, it can obviously cause skin thickening in the back of mice. However, in the experimental group, imiquimod and 100 mg of PT-A were given at the same time, which could reduce the skin disease in mice.

在基因表現量上，相較於控制組，對照組之IL-17、IL-23及IL-22均有明顯增加情形，然而於塗抹PT-A軟膏動物之組織，其基因表現量則有下降之趨勢；與對照組相較下，100mg PT-A組別之IL-17、IL-23及IL-22的表現量達顯著差異，而100mg PT-A組別之IL-22的表現量則具有顯著差異(* p<0.05，**p<0.01)(第4B圖)。 In terms of gene expression, compared with the control group, IL-17, IL-23, and IL-22 in the control group all increased significantly. However, in the tissues of animals with PT-A ointment, the gene expression decreased. Compared with the control group, the expression levels of IL-17, IL-23 and IL-22 in the 100 mg PT-A group were significantly different, while the expression levels of IL-22 in the 100 mg PT-A group were significantly different. Significant differences (* p <0.05, ** p <0.01) (Figure 4B).

此外，相對於對照組之給予咪喹莫特，在實驗組中之同時給予咪喹莫特與100mg PT-A後，可降低小鼠皮膚CD68、CD4、Neutrophils、Ki-67及CD31的表現量或數目(第4C圖)。 In addition, compared with the control group, the administration of imiquimod in the experimental group can reduce the expression of CD68, CD4, Neutrophils, Ki-67 and CD31 in mice. Or number (Figure 4C).

5.實施例5 5.Example 5

PT-A對降低1-氟-2,4-二硝基苯(1-fluoro-2,4-dinitrobenzene,DNFB)誘導動物接觸性皮膚炎之作用 Effect of PT-A on reducing 1-fluoro-2,4-dinitrobenzene (DNFB) -induced contact dermatitis in animals

本實施例中，透過1-氟-2,4-二硝基苯誘導動物接觸性皮膚炎模式來評估PT-A對降低接觸性皮膚疾病之影響。其實施步驟如下： In this example, the effect of PT-A on reducing contact skin diseases was evaluated by 1-fluoro-2,4-dinitrobenzene-induced contact dermatitis model in animals. The implementation steps are as follows:

將C57BL/6小鼠分成控制組、正對照組及實驗組以進行不同處理。首先將提供0.5% DNFB於各組小鼠(控制組、正對照組與實驗組之塗藥部，分別為腹部、耳朵與耳朵)，連續給予五天後，進行下述測試。 C57BL / 6 mice were divided into control group, positive control group and experimental group for different treatments. First, 0.5% DNFB was provided to the mice in each group (the control group, the positive control group and the experimental group were coated with the abdomen, ears and ears respectively), and the following tests were performed after five consecutive days of administration.

於控制組中，為將0.2% DNFB塗抹於小鼠腹部；於正對照組中，將臨得隆(Rinderon)(0.5mg/g)塗抹於小鼠耳朵；於實 驗組中，則將PT-A(50mg)軟膏塗抹於小鼠耳朵。 In the control group, 0.2% DNFB was applied to the abdomen of mice; in the positive control group, Rinderon (0.5mg / g) was applied to the ears of mice; In the test group, PT-A (50 mg) ointment was applied to mouse ears.

以上各別處理經過18小時後，再評估動物接觸性過敏反應之程度，並於動物犧牲後，進行發炎部位皮膚之CD4免疫組織染色分析。結果如第5A圖與第5B圖所示。 After 18 hours of each of the above treatments, the extent of the animal's contact allergic reaction was re-evaluated, and after the animal was sacrificed, CD4 immunohistochemical staining analysis was performed on the skin of the inflammation site. The results are shown in Figures 5A and 5B.

第5A圖與第5B圖顯示，相對於控制組之給予1-氟-2,4-二硝基苯，實驗組給予PT-A後，可降低小鼠皮膚增厚程度以及CD4浸潤數目，與正對照組給予Rinderon之試驗結果相近。 Figures 5A and 5B show that, compared with the control group given 1-fluoro-2,4-dinitrobenzene, the experimental group given PT-A can reduce the degree of skin thickening and CD4 infiltration in mice, and The positive control group gave similar results to Rinderon.

6.實施例6 6. Example 6

PT-A與市售產品之降低小鼠類乾癬皮膚疾病之功效評估比較 Evaluation of the efficacy of PT-A and commercially available products in reducing psoriasis-like skin diseases in mice

本實施例中，透過咪喹莫特誘導之類乾癬動物模式來評估PT-A與市售產品之功效比較。實施步驟如下： In this example, the efficacy comparison between PT-A and commercially available products was evaluated through the animal model of psoriasis induced by imiquimod. The implementation steps are as follows:

首先將Balb/c小鼠(6-8週齡)背部毛髮剃除，並將小鼠分成控制組、對照組以及三組實驗組，其中三組實驗組分別為PT-A(100mg)軟膏處理組、Rinderon-V(0.06%，台灣鹽野義)軟膏處理組以及Daivonex(0.005%,LEO Pharma)軟膏處理組。 First, the hair of Balb / c mice (6-8 weeks old) was shaved, and the mice were divided into a control group, a control group and three experimental groups, of which the three experimental groups were treated with PT-A (100 mg) ointment. Group, Rinderon-V (0.06%, Shiinoi, Taiwan) ointment treatment group and Daivonex (0.005%, LEO Pharma) ointment treatment group.

控制組中未給予小鼠任何處理；對照組則將62.5mg含咪喹莫特乳膏(Aldara；3M Pharmaceuticals)塗抹於小鼠背部，每天給予一次咪喹莫特乳膏，連續給予六天，以誘導小鼠皮膚乾癬症狀產生；而實驗組則將62.5mg咪喹莫特乳膏塗抹於小鼠背部，接著局部塗抹測試軟膏，每天給予一次咪喹莫特乳膏與測試軟膏，連續給予六天。 No treatment was given to the mice in the control group; 62.5 mg of imiquimod cream (Aldara; 3M Pharmaceuticals) was applied to the back of the control group, and imiquimod cream was administered once a day for six consecutive days. In order to induce the symptoms of psoriasis on the skin of mice, the experimental group applied 62.5mg of imiquimod cream to the back of the mice, and then applied the test ointment topically. The imiquimod cream and test ointment were given once a day for six consecutive times. day.

之後評估動物背部皮膚疾病之程度，包括發紅、脫屑等項目，並照相。將動物犧牲後，取其背部發炎部位皮膚進行 組織之基因表現量檢測，包括IL-17A、TNF-α、IL-6、S100A7等。結果如第6A圖與第6B圖所示。 The degree of skin disease on the back of the animal, including items such as redness and desquamation, was then assessed and photographed. After sacrificing the animal, take the skin from the back of the inflammation site Detection of tissue gene expression, including IL-17A, TNF-α, IL-6, S100A7, etc. The results are shown in Figures 6A and 6B.

第6A圖顯示，對照組相對於控制組在給予咪喹莫特後，可明顯造成小鼠皮膚發紅與脫屑現象，然而在實驗組中之同時給予咪喹莫特與PT-A或Rinderon後，則可減輕小鼠皮膚疾病現象。 Figure 6A shows that after the administration of imiquimod, the control group can significantly cause skin redness and desquamation in mice compared with the control group. However, in the experimental group, imiquimod and PT-A or Rinderon were given at the same time. Later, it can reduce the skin disease phenomenon in mice.

第6B圖，在基因表現量上，相較於控制組，對照組之IL-17A、TNF-α、IL-6及S100A7均有明顯增加情形，然而於塗抹PT-A或Rinderon軟膏動物之組織，其基因表現量則有下降之趨勢，其中以IL-6、TNF-α及S100A7之表現量與對照組相較下達顯著差異(* p<0.05，** p<0.01，***p<0.001)。Daivonex組別於TNF-α及S100A7之表現量與對照組相較下雖達顯著差異，但未明顯改善小鼠皮膚脫屑現象。 Figure 6B. In terms of gene expression, compared with the control group, IL-17A, TNF-α, IL-6, and S100A7 in the control group were significantly increased. However, the tissues of animals treated with PT-A or Rinderon ointment were significantly increased. , Its gene expression has a downward trend, in which the expression of IL-6, TNF-α and S100A7 is significantly different from the control group (* p <0.05, ** p <0.01, *** p < 0.001). Although the expression of Daivonex group over TNF-α and S100A7 was significantly different from the control group, it did not significantly improve the skin desquamation in mice.

7.實施例7 7.Example 7

PT-A與類固醇軟膏合併使用對降低小鼠類乾癬皮膚疾病之功效評估 Evaluation of the efficacy of PT-A combined with steroid ointment on reducing psoriasis-like skin disease in mice

透過咪喹莫特誘導之類乾癬動物模式來評估PT-A加上類固醇軟膏對於皮膚疾病之影響。其實施步驟如下： The effects of PT-A plus steroid ointments on skin diseases were evaluated in animal models of psoriasis induced by imiquimod. The implementation steps are as follows:

首先將Balb/c小鼠(6-8週齡)背部毛髮剃除，並將小鼠分成控制組、對照組以及三組實驗組，三組實驗組分別為BD(類固醇)軟膏處理組、BD+PT-A軟膏處理組(PT-A比BD之重量比為83：1)與Daivobet(LEO Pharma)軟膏處理組。各組每隻動物每次處理塗抹25mg軟膏。 First, Balb / c mice (6-8 weeks of age) were shaved off their back hair, and the mice were divided into control group, control group and three experimental groups. The three experimental groups were BD (steroid) ointment treatment group and BD. + PT-A ointment treatment group (PT-A to BD weight ratio is 83: 1) and Daivobet (LEO Pharma) ointment treatment group. Each animal in each group was treated with 25 mg of ointment.

控制組中將62.5mg之咪喹莫特乳膏(Aldara；3M Pharmaceuticals)塗抹於小鼠背部，每天給予一次咪喹莫特乳膏，連續給予六天，以誘導小鼠皮膚乾癬症狀產生；對照組則將62.5mg之咪喹莫特乳膏塗抹於小鼠背部，接著局部塗抹軟膏基劑；實驗組則將62.5mg之咪喹莫特乳膏塗抹於小鼠背部，接著局部塗抹測試軟膏，每天給予一次咪喹莫特乳膏與測試軟膏，連續給予六天。 In the control group, 62.5 mg of imiquimod cream (Aldara; 3M (Pharmaceuticals) was applied to the back of mice, and imiquimod cream was administered once a day for six consecutive days to induce the symptoms of psoriasis on the skin of the mice; the control group applied 62.5mg of imiquimod cream to the back of mice Then, the ointment base was applied topically; the experimental group applied 62.5 mg of imiquimod cream to the back of the mice, and then the test ointment was applied topically. The imiquimod cream and the test ointment were given once a day for six consecutive days. .

之後評估動物背部皮膚疾病之程度，包括脫屑、發紅等項目，且依照脫屑加發紅之嚴重程度給予0-8分(最嚴重者給予8分，無症狀者給予0分)並照相。將動物犧牲後，將其發炎部位皮膚取下浸泡於4%甲醛進行固定，接著將樣品以縱切成6μm厚度後，再以蘇木素-伊紅染色，以評估皮膚疾病程度，包括上皮厚度、角化不全或增生等，並分別以Ki-67抗體進行免疫組織染色，以評估皮膚疾病部位之細胞增生現象。結果如第7A圖至第7D圖所示。 Then evaluate the degree of skin diseases on the back of the animal, including desquamation, redness, etc., and give 0-8 points according to the severity of desquamation and redness (8 points for the most severe, 0 points for asymptomatic) and take pictures . After the animal was sacrificed, the skin of its inflamed area was removed and immersed in 4% formaldehyde for fixation, and then the sample was cut to a thickness of 6 μm and then stained with hematoxylin-eosin to evaluate the degree of skin disease, including epithelial thickness, horn Insufficiency or hyperplasia, etc., and immunohistochemical staining with Ki-67 antibody, respectively, to evaluate cell proliferation in skin disease sites. The results are shown in Figures 7A to 7D.

依據第7A圖至第7D圖可知，控制組在給予咪喹莫特後，可明顯造成小鼠皮膚出現發紅、脫屑及上皮增厚現象(第7A圖與第7C圖)，然而在實驗組中同時給予咪喹莫特與BD+PT-A後，則可減輕小鼠皮膚疾病現象，包括顯著減輕脫屑及發紅現象(第7B圖)，與控制組相較下達顯著差異(* p<0.05，** p<0.01，***p<0.001)，減少上皮增厚(第7C圖)以及減少Ki-67表現量(第7D圖)，反觀BD與Daivobet實驗組則無法顯著改善小鼠皮膚疾病現象。 Based on Figures 7A to 7D, it can be seen that after the administration of imiquimod in the control group, the skin of the mice can obviously cause redness, desquamation, and thickening of the epithelium (Figures 7A and 7C). However, in the experiment, The combination of imiquimod and BD + PT-A in the group can reduce the skin disease phenomenon in mice, including significantly reducing the phenomenon of desquamation and redness (Figure 7B), which is significantly different from the control group (* p <0.05, ** p <0.01, *** p <0.001), reducing epithelial thickening (Figure 7C) and reducing Ki-67 performance (Figure 7D), in contrast, the BD and Daivobet experimental groups could not improve significantly. Skin disease in mice.

8.實施例8 8.Example 8

PT-A與中效類固醇軟膏合併使用與強酵類固醇對降 低小鼠類乾癬皮膚疾病之功效比較 Combination of PT-A and intermediate-acting steroid ointment with strong fermenting steroids Comparison of efficacy of psoriasis-like skin diseases in low mice

透過咪喹莫特誘導之類乾癬動物模式來評估PT-A加上中效類固醇軟膏對於皮膚疾病的影響。其實施步驟如下： The effects of PT-A plus intermediate-acting steroid ointments on skin diseases were evaluated in animal models of psoriasis induced by imiquimod. The implementation steps are as follows:

首先將C57BL/6小鼠(6~8週齡)背部毛髮剃除，並將小鼠分成控制組、對照組以及五組實驗組，五組實驗組分別為氟輕松(fluocinonide)(0.05%；中效類固醇)軟膏處理組、氟輕松+PT-A(0.25%)軟膏處理組(PT-A比氟輕松之重量比為5：1)、氟輕松+PT-A(5%)軟膏處理組(PT-A比氟輕松之重量比為100：1)、PT-A(5%)軟膏處理組以及丙酸氯氟美松(clobetasol propionate)(0.05%)軟膏處理組。各組每隻動物每次處理塗抹25mg軟膏。 First, C57BL / 6 mice (6-8 weeks old) were shaved off their back hair, and the mice were divided into control group, control group and five experimental groups. The five experimental groups were fluocinonide (0.05%; Intermediate steroid) ointment treatment group, fluocinolone + PT-A (0.25%) ointment treatment group (PT-A to fluocinolone weight ratio is 5: 1), fluocinolone + PT-A (5%) ointment treatment group (The weight ratio of PT-A to fluocinolone is 100: 1), the PT-A (5%) ointment treatment group and the clobetasol propionate (0.05%) ointment treatment group. Each animal in each group was treated with 25 mg of ointment.

控制組中將62.5mg之咪喹莫特乳膏(Aldara；3M Pharmaceuticals)塗抹於小鼠背部，每天給予一次咪喹莫特乳膏，連續給予六天，以誘導小鼠皮膚乾癬症狀產生；對照組則將62.5mg之咪喹莫特乳膏塗抹於小鼠背部，接著局部塗抹軟膏基劑；實驗組則將62.5mg之咪喹莫特乳膏塗抹於小鼠背部，接著局部塗抹25mg之測試軟膏，每天給予一次咪喹莫特乳膏與測試軟膏，連續給予六天。 In the control group, 62.5 mg of imiquimod cream (Aldara; 3M Pharmaceuticals) was applied to the backs of the mice, and imiquimod cream was administered once a day for six consecutive days to induce the symptoms of skin psoriasis in mice; control In the group, 62.5mg of imiquimod cream was applied to the back of the mouse, and then the ointment base was applied topically. In the experimental group, 62.5mg of imiquimod cream was applied to the back of the mouse, and then 25mg was applied topically. Ointment, imiquimod cream and test ointment were given once a day for six consecutive days.

之後評估動物背部皮膚疾病之程度，包括脫屑、發紅及皮膚厚度等三個項目，且依照以上三項個別之嚴重程度給予0-12分(最嚴重者給予12分，無症狀者給予0分)並照相。將動物犧牲後，將其發炎部位皮膚取下浸泡於4%甲醛進行固定，接著將樣品以縱切成6μm厚度後，再以蘇木素-伊紅染色，以評估皮膚疾病程度，包括上皮厚度、角化不全或增生等。結果如第8A-1、8A-2、8B-1、8B-2與8C圖所示。 Then evaluate the degree of skin disease on the back of the animal, including three items such as desquamation, redness, and skin thickness, and give 0-12 points according to the above three individual severity (12 points for the most severe, 0 for asymptomatic) Points) and take pictures. After the animal was sacrificed, the skin of its inflamed area was removed and immersed in 4% formaldehyde for fixation, and then the sample was cut to a thickness of 6 μm and then stained with hematoxylin-eosin to evaluate the degree of skin disease, including epithelial thickness, horn Incomplete or hyperplasia. The results are shown in Figures 8A-1, 8A-2, 8B-1, 8B-2, and 8C.

依據第8A-1與8A-2及第8B-1與8B-2圖可知，相較於控制組，實驗組同時給予氟輕松+PT-A後，可減輕小鼠皮膚疾病現象，包括減輕發紅、脫屑及上皮增厚現象(第8A-1與8A-2及第8B-1與8B-2圖)，且與控制組相較，顯示顯著差異(** p<0.01，***p<0.001)(第8C圖)。其中，相較於氟輕松處理組，實驗組之氟輕松+PT-A，可提高小鼠皮膚疾病之改善程度，包括減輕發紅、脫屑及上皮增厚現象(第8A-1與8A-2及第8B-1與8B-2圖)，尤其是氟輕松+PT-A(0.25%)軟膏處理組，且與氟輕松組相較，顯示顯著差異(## p<0.01)(第8C圖)。而氟輕松+PT-A(5%)軟膏處理組雖有提高改善程度之趨勢，但與氟輕松組相較未達顯著差異(not significant,ns)。 According to Figures 8A-1 and 8A-2 and Figures 8B-1 and 8B-2, it can be seen that compared with the control group, the experimental group can be treated with fluocinolone + PT-A at the same time, which can reduce the skin disease phenomenon in mice, including reducing hair loss. Redness, desquamation, and thickening of the epithelium (Figures 8A-1 and 8A-2 and Figures 8B-1 and 8B-2), and compared with the control group, showed significant differences (** p <0.01, *** p <0.001) (Figure 8C). Among them, compared with the fluorinated treatment group, the fluorinated treatment + PT-A in the experimental group can improve the degree of skin disease improvement in mice, including reducing redness, desquamation and thickening of epithelium (Sections 8A-1 and 8A- 2 and Figures 8B-1 and 8B-2), especially the fluocinolone + PT-A (0.25%) ointment treatment group, and compared with the fluocinolone group, it shows a significant difference (## p <0.01) (# 8C Figure). The fluocinolone + PT-A (5%) ointment treatment group had a tendency to improve the degree of improvement, but it did not reach a significant difference (not significant, ns) compared with the fluocinolone group.

9.實施例9 9.Example 9

PT-A對影響小鼠耳朵皮膚厚度之分析 Analysis of PT-A on the thickness of mouse ear skin

首先將ICR小鼠(7-9週齡)分成控制組(媒劑(Vehicle))以及三組實驗組，其中三組實驗組分別為PT-A(含量25mg/g)軟膏處理組、可立舒乳膏(CLOBETASOL Cream，混合乳膏基劑丙酸氯氟美松含量為0.25mg/g)處理組以及妥膚淨親水軟膏(TOPSYM Cream，混合乳膏基劑氟輕松含量為0.25mg/g)處理組。 First, ICR mice (7-9 weeks of age) were divided into control group (vehicle) and three experimental groups, of which the three experimental groups were PT-A (content 25mg / g) ointment-treated group, and Keli The treatment group of CLOBETASOL Cream (clofetasone propionate, 0.25 mg / g mixed cream base) and TOPSYM Cream (TOPSYM Cream, mixed cream base, fluocinolone content of 0.25 mg / g) ) Processing group.

控制組耳朵每天塗抹一次乳膏基劑(不含有效成分)10mg；而實驗組則耳朵每天分別塗抹一次10mg之測試乳膏，連續塗抹十四天。 The control group applied 10 mg of cream base (without active ingredients) once a day; the experimental group applied 10 mg of test cream once a day for 14 days.

塗藥前以及塗藥後每2至4天測量耳朵厚度，並將塗藥前之耳朵厚度設為100%，觀察耳朵厚度變化情形。將動物犧牲 後，將其發炎部位皮膚取下浸泡於4%甲醛進行固定，接著將樣品以縱切成6μm厚度後，再以蘇木素-伊紅染色，以評估皮膚疾病程度，包括上皮厚度、角化不全或增生等。結果如第9A圖與第9B圖所示。 Measure ear thickness before and every 2 to 4 days after application, and set the ear thickness before application to 100%, and observe the change in ear thickness. Sacrifice the animal Then, the skin of the inflamed area was removed and immersed in 4% formaldehyde for fixation, and then the sample was cut to a thickness of 6 μm, and then stained with hematoxylin-eosin to evaluate the degree of skin diseases, including epithelial thickness, incomplete keratosis, or Hyperplasia, etc. The results are shown in Figures 9A and 9B.

依據第9A圖與第9B圖可知，PT-A實驗組之耳朵厚度變化與控制組一致，並未造成明顯變化，然而在實驗組之可立舒乳膏及妥膚淨親水軟膏兩組塗藥7至14天後，其耳朵厚度分別為塗藥前厚度的71-79%及80-81%，有明顯變薄之趨勢(與控制組比較，*p<0.05，**p<0.01)。 According to Figures 9A and 9B, it can be seen that the ear thickness changes in the PT-A experimental group are consistent with the control group and have not caused significant changes. However, in the experimental group, Kelishu cream and Tuofujing ointment were applied in two groups. After 7 to 14 days, the ear thickness was 71-79% and 80-81% of the thickness before application, respectively, and there was a clear tendency to thin (compared with the control group, * p <0.05, ** p <0.01).

10.實施例10 10.Example 10

PT-A對於降低類固醇所造成之皮膚厚度之影響分析 Effect of PT-A on reducing skin thickness caused by steroids

本實施例中，連續塗抹混有類固醇之PT-A軟膏評估其對於耳朵皮膚厚度之影響。其實施步驟如下： In this example, the effect of PT-A ointment mixed with steroids on the thickness of ear skin was continuously applied. The implementation steps are as follows:

首先將ICR小鼠(7-9週齡)分成控制組(媒劑)、對照組(Clobetasol)及兩組實驗組，其中兩組實驗組分別為PT-A(含量25mg/g)軟膏處理組與PT-A(含量25mg/g)混合可立舒乳膏(CLOBETASOL Cream含量0.25mg/g)(Clobetasol+PT-A)(PT-A比CLOBETASOL之重量比為100：1)之軟膏處理組。 First, ICR mice (7-9 weeks of age) were divided into control group (vehicle), control group (Clobetasol) and two experimental groups, of which the two experimental groups were PT-A (content 25mg / g) ointment treatment group Ointment treatment group that was mixed with PT-A (content 25mg / g), Kelishu cream (CLOBETASOL Cream content 0.25mg / g) (Clobetasol + PT-A) (PT-A to CLOBETASOL weight ratio 100: 1) .

控制組耳朵每天塗抹一次乳膏基劑(不含有效成分)10mg；對照組耳朵每天塗抹一次10mg之可立舒乳膏(CLOBETASOL Cream，混合乳膏基劑後丙酸氯氟美松含量0.25mg/g)；實驗組兩組則耳朵每天分別塗抹一次10mg之測試軟膏，連續塗抹14天。 The control group applied 10 mg of cream base (without active ingredients) once a day; the control group applied 10 mg of CLOBETASOL Cream once a day, and mixed the cream base with clofometasone propionate 0.25 mg. 10g of test ointment were applied to the ears of the two groups in the experimental group once a day for 14 consecutive days.

塗藥前以及塗藥後每2至4天測量耳朵厚度，並將塗 藥前之耳朵厚度設為100%，觀察耳朵厚度變化情形。將動物犧牲後，將其發炎部位皮膚取下浸泡於4%甲醛進行固定，接著將樣品以縱切成6μm厚度後，再以蘇木素-伊紅染色，以評估皮膚疾病程度，包括上皮厚度、角化不全或增生等。結果如第10A圖與第10B圖所示。 Measure ear thickness before and every 2 to 4 days after application, and apply The ear thickness before the medicine was set to 100%, and the change in ear thickness was observed. After the animal was sacrificed, the skin of its inflamed area was removed and immersed in 4% formaldehyde for fixation, and then the sample was cut to a thickness of 6 μm and then stained with hematoxylin-eosin to evaluate the degree of skin disease, including epithelial thickness, horn Incomplete or hyperplasia. The results are shown in Figures 10A and 10B.

依據第10A圖與第10B圖可知，實驗組之PT-A組耳朵厚度變化與控制組一致，並未造成明顯變化；實驗組之PT-A混合可立舒乳膏組耳朵厚度明顯變薄，塗藥7至14天後為塗藥前厚度的77-83%，與對照組71-79%相近(與控制組比較，* p<0.05，**p<0.01)，然而PT-A混合可立舒乳膏組塗藥後3天約為塗藥前厚度的86%，明顯較對照組73%厚(與對照組比較，# p<0.05)。 According to Figures 10A and 10B, it can be seen that the ear thickness of the PT-A group in the experimental group is consistent with the control group without causing significant changes; the ear thickness of the PT-A mixed Kelishu cream group in the experimental group is significantly thinner. 7 to 14 days after application, it is 77-83% of the thickness before application, which is similar to the control group of 71-79% (compared with the control group, * p <0.05, ** p <0.01), but PT-A mixed can The Lishu cream group was about 86% of the thickness before the application 3 days after application, which was significantly thicker than the control group by 73% (compared with the control group, # p <0.05).

11.實施例11 11.Example 11

PT-A與市售產品引起皮膚不良反應之作用評估比較 Comparison of effects of PT-A and commercial products on skin adverse reactions

首先將C57BL/6小鼠(6-8週齡)背部毛髮剃除，並將小鼠分成控制組、對照組以及實驗組。 First, C57BL / 6 mice (6-8 weeks of age) were shaved with their back hair, and the mice were divided into control group, control group and experimental group.

於控制組中未給予小鼠任何處理；於對照組中則將10mg Rinderon軟膏塗抹於小鼠背部，每天給予一次，連續給予60天；而於實驗組中則將10mg PT-A軟膏塗抹於小鼠背部，每天給予一次，連續給予60天。 No treatment was given to the mice in the control group; 10 mg of Rinderon ointment was applied to the back of the mice in the control group, once a day for 60 days; and 10 mg of PT-A ointment was applied to the experimental group. The rats were given back once a day for 60 days.

之後評估動物背部皮膚不良反應之程度，包括乾燥、發紅、脫屑等項目，並照相。將動物犧牲後，取其背部未塗抹軟膏部位之皮膚(控制組)或塗抹軟膏部位之(對照組及實驗組)皮膚進行組織之蘇木素-伊紅染色，結果如第11A圖與第11B圖所示。 The extent of adverse skin reactions, including dryness, redness, and desquamation, was evaluated and photographed. After sacrificing the animals, take the hematoxylin-eosin staining of the tissue on the back of the skin (control group) or on the skin (control group and experimental group) where the ointment is not applied. The results are shown in Figures 11A and 11B. Show.

第11A圖顯示，對照組相對於控制組在給予Rinderon後，可明顯造成小鼠皮膚乾燥與脫屑現象，然而在實驗組中給予PT-A 60天後，小鼠皮膚維持正常外觀，與控制組相同。 Figure 11A shows that after the administration of Rinderon, the control group can significantly cause dryness and desquamation of the skin of the mice. However, after the administration of PT-A in the experimental group for 60 days, the skin of the mice maintained a normal appearance. The group is the same.

第11B圖顯示，對照組相對於控制組可明顯造成小鼠表皮變薄現象，然而在實驗組中給予PT-A 60天後，小鼠皮膚表皮維持正常厚度，與控制組相同。 Figure 11B shows that the control group can significantly reduce the epidermis of the mice compared to the control group. However, 60 days after the administration of PT-A in the experimental group, the skin epidermis of the mice maintained a normal thickness, the same as that of the control group.

12.實施例12 12.Example 12

人類皮膚重覆刺激性與過敏性試驗結果。 Repeated irritation and allergic test results on human skin.

本實施例中，共測試50個受試者，首先將PT-A(含量25mg/g)軟膏塗於低敏性之貼布上，再覆蓋於受試者之背後肩胛骨下區域。於24小時之後，拆除貼布。每隔2天重覆測試，於一週內進行3次測試，連續3週進行刺激性試驗。於第2-9次測試前以及進行過敏性試驗前，觀察皮膚發紅與水腫情形，共9次結果。 In this example, a total of 50 subjects were tested. First, a PT-A (content 25mg / g) ointment was applied to a low-sensitivity patch, and then the subscapular area behind the subject was covered. After 24 hours, remove the patch. Repeat the test every 2 days, perform 3 tests within a week, and perform the irritation test for 3 consecutive weeks. Before the 2-9th test and before the allergy test, the skin redness and edema were observed. A total of 9 results were obtained.

10-14天後，50個受試者再次以PT-A(含量25mg/g)軟膏塗抹於其背後肩胛骨下區域。於24與48小時後，分別評估其皮膚發紅與水腫情形，此為過敏性試驗。結果如第12圖所示。。 After 10-14 days, 50 subjects were reapplied with PT-A (25mg / g) ointment to the subscapular area behind their backs. After 24 and 48 hours, the skin redness and edema were evaluated, and this was an allergy test. The results are shown in Figure 12. .

第12圖結果顯示，PT-A不會引起人類皮膚刺激性與過敏性反應。 Figure 12 shows that PT-A does not cause irritating and allergic reactions to human skin.

13.實施例13 13.Example 13

PT-A於大白兔皮膚重覆刺激性試驗結果 Repeated irritation test results of PT-A on the skin of white rabbits

首先將3隻2.0-3.0kg紐西蘭大白兔背部毛髮剃除，再將PT-A(含量25mg/g)軟膏塗於1吋×1吋大小之紗布上，並以人工敷料固定貼附於背部之右側區域24小時後，拆除紗布及人工敷料，並以蒸餾水清洗受測皮膚，連續17天塗抹。對照物質 (前10天為注射用蒸餾水，後7天為無樣品軟膏)，則同樣塗於相同大小之紗布上，並以人工敷料固定貼附於左側區域。24小時後，拆除紗布及人工敷料，並以蒸餾水清洗受測皮膚，連續17天塗抹。 First, shave the back hair of three 2.0-3.0kg New Zealand white rabbits, and then apply PT-A (content 25mg / g) ointment on a gauze of 1 inch x 1 inch, and fix it with artificial dressing. After 24 hours on the right side of the back, remove the gauze and artificial dressing, and wash the skin under test with distilled water, and apply it for 17 consecutive days. Reference substance (The first 10 days is distilled water for injection, and the next 7 days is sample-free ointment), then apply the same size to the gauze of the same size, and fix it on the left area with artificial dressing. After 24 hours, remove the gauze and artificial dressing, and wash the test skin with distilled water, and apply it for 17 consecutive days.

每天拆除人工敷料及紗布後，開始觀察動物皮膚是否產生紅斑及浮腫情形，觀察時間連續17天。依皮膚反應判定基準表加以評分，再以此評分之分數計算出皮膚單次刺激性係數PII(primary irritation index)，得出之係數評估皮膚在測試物質重覆投予後所產生之刺激反應，結果如表1所示。 After removing the artificial dressing and gauze every day, start to observe whether the skin of the animal has erythema and edema, and the observation time is 17 consecutive days. Scoring according to the skin response judgment reference table, and then calculating the skin's single irritation coefficient PII (primary irritation index) based on the score, the obtained coefficient evaluates the skin's irritation response after repeated administration of the test substance. Results As shown in Table 1.

Figure TWI610679BD00001
Figure TWI610679BD00001
Figure TWI610679BD00002
Figure TWI610679BD00002

原發刺激分數(primary irritation score,PIS) Primary irritation score (PIS)

原發刺激分數=實驗組分數-對照組分數 Primary stimulation score = number of experimental components-control group score

編號1001：19-3=16 Number 1001: 19-3 = 16

編號1002：0-0=0 Number 1002: 0-0 = 0

編號1003：8-1=7 Number 1003: 8-1 = 7

皮膚單次刺激性係數PII Skin single irritation coefficient PII

皮膚單次刺激性係數PII=原發刺激分數分數/測試天數 Skin single irritation coefficient PII = score of primary irritation / test days

編號1001：16/17=0.9(輕度刺激) No. 1001: 16/17 = 0.9 (mild stimulation)

編號1002：0/17=0(無刺激) No. 1002: 0/17 = 0 (no stimulation)

編號1003：7-17=0.4(無刺激) No. 1003: 7-17 = 0.4 (no stimulation)

表1結果顯示，PT-A軟膏於1隻動物顯示為輕度刺激性反應，其餘2隻則為無刺激性。 The results in Table 1 show that PT-A ointment showed a mild irritant response in one animal and the other two were non-irritating.

雖然本發明已以較佳實施例揭露如上，然其並非用以限定本發明，任何熟習此技藝者，在不脫離本發明之精神和範圍內，當可作些許之更動與潤飾，因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。 Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications and retouching without departing from the spirit and scope of the present invention. Therefore, the present invention The scope of protection shall be determined by the scope of the attached patent application.

Claims (32)

一種中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該中草藥乙醇萃取物的一製備原料係由甘草、柴胡、黃芩、五味子與芍藥所組成。 A Chinese herbal medicine ethanol extract is used for preparing a medicine for treating skin diseases. A raw material for preparing the Chinese herbal medicine ethanol extract is composed of licorice, bupleurum, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora. 如申請專利範圍第1項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中於該製備原料中，該甘草、該柴胡、該黃芩、該五味子與該芍藥的重量比為約1-5：1-5：1-5：1-5：1-5。 The use of the Chinese herbal medicine ethanol extract as described in item 1 of the patent scope for preparing a medicine for treating skin diseases, wherein in the preparation raw material, the weight ratio of the licorice root, the bupleurum root, the scutellaria baicalensis, the Schisandra chinensis and the peony It is about 1-5: 1-5: 1-5: 1-5: 1-5: 1-5. 如申請專利範圍第1項所述之中草乙醇藥萃取物用於製備治療皮膚疾病之藥物的用途，其中該中草藥乙醇萃取物係藉由包括以下步驟之一萃取方法所獲得：(a)將該製備原料中之甘草、柴胡、黃芩、五味子與芍藥混合以形成一原料混合物；以及(b)將該原料混合物以乙醇進行一萃取製程。 The use of Chinese herbal medicine ethanol extract as described in item 1 of the scope of patent application for preparing a medicine for treating skin diseases, wherein the Chinese herbal medicine ethanol extract is obtained by an extraction method including one of the following steps: (a) Licorice, Bupleurum, Scutellaria baicalensis, Schisandra chinensis and Paeonia lactiflora in the prepared raw materials are mixed to form a raw material mixture; and (b) the raw material mixture is subjected to an extraction process with ethanol. 如申請專利範圍第1項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該甘草包括生甘草或炙甘草，該柴胡包括生北柴胡或高氏柴胡，該黃芩包括枯黃芩或條黃芩，該五味子包括北五味子或南五味子，而該芍藥包括赤芍、白芍或牡丹。 The use of the Chinese herbal medicine ethanol extract as described in item 1 of the scope of the patent application for preparing a medicine for treating skin diseases, wherein the licorice includes raw licorice or licorice root, the Bupleurum includes raw North Bupleurum or Gao Bupleurum, the Scutellaria baicalensis includes Scutellaria baicalensis or Scutellaria baicalensis, the Schisandra chinensis comprises northern Schisandra chinensis or southern Schisandra chinensis, and the paeonia lactiflora includes red peony, white peony or peony. 如申請專利範圍第1項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該甘草為生甘草、該柴胡為北柴胡、該黃芩為枯黃芩、該五味子為北五味子且該 芍藥為赤芍。 The use of the Chinese herbal medicine ethanol extract as described in item 1 of the scope of patent application for the preparation of a medicament for treating skin diseases, wherein the licorice is raw licorice, the Bupleurum is Bei Chai Hu, the Scutellaria baicalensis is withered Scutellaria baicalensis, and the Schisandra chinensis is Bei Schisandra chinensis Paeonia lactiflora is red peony. 如申請專利範圍第5項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中於該製備原料中，該生甘草、該北柴胡、該枯黃芩、該北五味子與該赤芍的重量比為約1：1：1：1：1。 The use of the Chinese herbal medicine ethanol extract as described in item 5 of the scope of patent application for preparing a medicine for treating skin diseases, wherein in the preparation raw material, the raw licorice root, the beihaihu, the withered scutellaria baicalensis, the north schisandra and the The weight ratio of red peony is about 1: 1: 1: 1: 1: 1. 如申請專利範圍第6項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該中草藥乙醇萃取物係藉由包括以下步驟之一萃取方法所獲得：將該製備原料中之該生甘草、該北柴胡、該枯黃芩、該北五味子與該赤芍混合以形成一原料混合物；以及將該原料混合物以乙醇進行一萃取製程。 The use of the Chinese herbal medicine ethanol extract as described in item 6 of the application for preparing a medicine for treating skin diseases, wherein the Chinese herbal medicine ethanol extract is obtained by an extraction method including one of the following steps: The raw licorice, the beihaihu, the scutellaria baicalensis, the schisandra chinensis and the red schisandra are mixed to form a raw material mixture; and the raw material mixture is subjected to an extraction process with ethanol. 如申請專利範圍第1項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該皮膚疾病包括自體免疫相關皮膚疾病或感染性皮膚疾病。 The use of the Chinese herbal medicine ethanol extract as described in item 1 of the scope of the patent application for preparing a medicine for treating skin diseases, wherein the skin diseases include autoimmune-related skin diseases or infectious skin diseases. 如申請專利範圍第8項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該自體免疫相關皮膚疾病包括乾癬、過敏性皮膚炎或異位性皮膚炎。 The use of the Chinese herbal medicine ethanol extract as described in item 8 of the scope of patent application for preparing a medicine for treating skin diseases, wherein the autoimmune-related skin diseases include psoriasis, allergic dermatitis or atopic dermatitis. 如申請專利範圍第1項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該治療皮膚疾病之藥物為局部給藥劑型，且該局部給藥劑型包括軟膏、乳劑、液劑或凝膠。 The use of the Chinese herbal medicine ethanol extract as described in item 1 of the scope of patent application for preparing a medicine for treating skin diseases, wherein the medicine for treating skin diseases is a topical dosage form, and the topical dosage form includes an ointment, an emulsion, a liquid Agent or gel. 如申請專利範圍第1項所述之中草藥乙醇萃取物用於製備 治療皮膚疾病之藥物的用途，更包括將該中草藥乙醇萃取物與一類固醇一起用於製備治療皮膚疾病之藥物的用途。 Chinese herbal medicine ethanol extract as described in the first patent application scope for preparation The use of a medicine for treating skin diseases further includes the use of the Chinese herbal medicine ethanol extract together with a steroid for preparing a medicine for treating skin diseases. 如申請專利範圍第11項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該中草藥乙醇萃取物與該類固醇之重量比為約5：1-200：1。 The use of the Chinese herbal medicine ethanol extract as described in item 11 of the scope of the patent application for preparing a medicine for treating skin diseases, wherein the weight ratio of the Chinese herbal medicine ethanol extract to the steroid is about 5: 1-200: 1. 如申請專利範圍第11項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該類固醇包括***、氟米、甲羥松、倍他米松、曲安西龍、潑尼松、潑尼松龍或氫化可的松。 The use of the Chinese herbal medicine ethanol extract as described in item 11 of the scope of patent application for the preparation of a medicament for treating skin diseases, wherein the steroid includes dexamethasone, flume, methasone, betamethasone, triamcinolone, prednisolone Pine, prednisolone or hydrocortisone. 如申請專利範圍第11項所述之中草藥乙醇萃取物用於製備治療皮膚疾病之藥物的用途，其中該治療皮膚疾病之藥物為局部給藥劑型，且該局部給藥劑型包括軟膏、乳劑、液劑或凝膠。 The use of the Chinese herbal medicine ethanol extract as described in item 11 of the scope of patent application for preparing a medicine for treating skin diseases, wherein the medicine for treating skin diseases is a topical dosage form, and the topical dosage form includes an ointment, an emulsion, a liquid Agent or gel. 一種中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該中草藥乙醇萃取物的一製備原料係由甘草、柴胡、黃芩、五味子與芍藥所組成。 A Chinese herbal medicine ethanol extract is used for preparing medicines for improving the side effects of steroids for treating skin diseases, wherein a preparation raw material of the Chinese herbal medicine ethanol extract is composed of licorice, bupleurum, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中於該製備原料中，該甘草、該柴胡、該黃芩、該五味子與該芍藥的重量比為約1-5：1-5：1-5：1-5：1-5。 The use of the Chinese herbal medicine ethanol extract as described in item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of steroids for the treatment of skin diseases, wherein in the preparation raw material, the licorice, the bupleurum, the scutellaria baicalensis, the schisandra and The weight ratio of the peony is about 1-5: 1-5: 1-5: 1-5: 1-5: 1-5. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其 中該中草藥乙醇萃取物係藉由包括以下步驟之一萃取方法所獲得：(a)將該製備原料中之甘草、柴胡、黃芩、五味子與芍藥混合以形成一原料混合物；以及(b)將該原料混合物以乙醇進行一萃取製程。 The use of Chinese herbal medicine ethanol extract as described in item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of treating skin diseases with steroids, which The Chinese herbal medicine ethanol extract is obtained by an extraction method including one of the following steps: (a) mixing licorice root, bupleurum, scutellaria baicalensis, Schisandra chinensis and peony in the preparation raw material to form a raw material mixture; and (b) mixing The raw material mixture is subjected to an extraction process with ethanol. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該甘草包括生甘草或炙甘草，該柴胡包括生北柴胡或高氏柴胡，該黃芩包括枯黃芩或條黃芩，該五味子包括北五味子或南五味子，而該芍藥包括赤芍、白芍或牡丹。 The use of the Chinese herbal medicine ethanol extract as described in item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of steroids for the treatment of skin diseases, wherein the licorice includes raw licorice or licorice, and the chaihu includes Bupleurum, the Scutellaria baicalensis includes Scutellaria baicalensis or Scutellaria baicalensis, the Schisandra chinensis comprises northern Schisandra chinensis or southern Schisandra chinensis, and the paeonia lactiflora includes red peony, white peony or peony. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該甘草為生甘草、該柴胡為北柴胡、該黃芩為枯黃芩、該五味子為北五味子且該芍藥為赤芍。 The Chinese herbal medicine ethanol extract according to item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of steroids for treating skin diseases, wherein the licorice is raw licorice, the Bupleurum is Bei Chaihu, and the Scutellaria baicalensis is withered The Schisandra chinensis is northern Schisandra chinensis and the peony is red peony. 如申請專利範圍第19項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中於該製備原料中，該生甘草、該北柴胡、該枯黃芩、該北五味子與該赤芍的重量比為約1：1：1：1：1。 The use of Chinese herbal medicine ethanol extract as described in item 19 of the scope of patent application for the preparation of a medicament for improving the side effects of steroids for treating skin diseases, wherein in the preparation raw material, the raw licorice root, the beihaihu, the scutellaria baicalensis, The weight ratio of the Schisandra chinensis to the red scallion is about 1: 1: 1: 1: 1: 1. 如申請專利範圍第20項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該中草藥乙醇萃取物係藉由包括以下步驟之一萃取方法所獲得： 將該製備原料中之生甘草、該北柴胡、該枯黃芩、該北五味子與該赤芍混合以形成一原料混合物；以及將該原料混合物以乙醇進行一萃取製程。 The use of the Chinese herbal medicine ethanol extract as described in item 20 of the patent application for preparing a medicament for improving the side effects of steroids for treating skin diseases, wherein the Chinese herbal medicine ethanol extract is obtained by an extraction method including one of the following steps: The raw licorice, the beihaihu, the scutellaria baicalensis and the Schisandra chinensis in the preparation raw material are mixed with the red scallion to form a raw material mixture; and the raw material mixture is subjected to an extraction process with ethanol. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該皮膚疾病包括感染性皮膚疾病或自體免疫相關皮膚疾病。 The use of the Chinese herbal medicine ethanol extract as described in item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of steroid treatment of skin diseases, wherein the skin diseases include infectious skin diseases or autoimmune-related skin diseases. 如申請專利範圍第22項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該自體免疫相關皮膚疾病包括乾癬、過敏性皮膚炎或異位性皮膚炎。 The use of the Chinese herbal medicine ethanol extract as described in item 22 of the patent application for the preparation of a medicament for improving the side effects of steroids for treating skin diseases, wherein the autoimmune-related skin diseases include psoriasis, allergic dermatitis or atopic skin inflammation. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該副作用包括皮膚變薄及/或血管擴張。 The use of the Chinese herbal medicine ethanol extract as described in item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of steroid treatment of skin diseases, wherein the side effects include skin thinning and / or vasodilation. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該類固醇包括***，氟米，甲羥松，倍他米松，曲安西龍，潑尼松，潑尼松龍或氫化可的松。 The use of Chinese herbal medicine ethanol extract as described in item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of steroids for the treatment of skin diseases, wherein the steroid includes dexamethasone, flume, methasone, betamethasone, koji Ansiron, prednisone, prednisone or hydrocortisone. 如申請專利範圍第15項所述之中草藥乙醇萃取物用於製備改善以類固醇治療皮膚疾病之副作用之藥物的用途，其中該改善以類固醇治療皮膚疾病之副作用之藥物為局部給藥劑型，且該局部給藥劑型包括軟膏、乳劑、液劑或凝膠。 The use of Chinese herbal medicine ethanol extract as described in item 15 of the scope of patent application for the preparation of a medicament for improving the side effects of steroids for treating skin diseases, wherein the medicament for improving the side effects of steroids for treating skin diseases is a topical dosage form, and the Topical dosage forms include ointments, creams, liquids or gels. 一種減緩皮膚疾病之醫藥組成物，包括：一中藥乙醇萃取物，其中該中草藥乙醇萃取物的一製備原料係由甘草、柴胡、黃芩、五味子與芍藥所組成；以及一類固醇，其中該中藥乙醇萃取物具有降低該類固醇所產生之副作用的功效及/或及/或相較於單獨使用該類固醇具有降低該類固醇所需之有效劑量的功效。 A medicinal composition for alleviating skin diseases, comprising: a Chinese medicine ethanol extract, wherein a preparation raw material of the Chinese herbal medicine ethanol extract is composed of licorice root, bupleurum, scutellaria baicalensis, Schisandra chinensis and paeonia lactiflora; and a steroid, wherein the Chinese medicine ethanol The extract has the effect of reducing the side effects produced by the steroid and / or has the effect of reducing the effective dose required for the steroid compared to using the steroid alone. 如申請專利範圍第27項所述之減緩皮膚疾病之醫藥組成物，其中於該製備原料中，該甘草、該柴胡、該黃芩、該五味子與該芍藥的重量比為約1-5：1-5：1-5：1-5：1-5。 The pharmaceutical composition for reducing skin diseases according to item 27 of the scope of the patent application, wherein in the preparation raw material, the weight ratio of the licorice root, the bupleurum root, the scutellaria baicalensis, the schisandra and the peony is about 1-5: 1 -5: 1-5: 1-5: 1-5. 如申請專利範圍第27項所述之減緩皮膚疾病之醫藥組成物，其中該中草藥乙醇萃取物與該類固醇之重量比為約5：1-200：1。 As described in item 27 of the scope of patent application, the medical composition for reducing skin diseases, wherein the weight ratio of the Chinese herbal medicine ethanol extract to the steroid is about 5: 1-200: 1. 如申請專利範圍第27項所述之減緩皮膚疾病之醫藥組成物，其中該類固醇包括***、氟米、甲羥松、倍他米松，曲安西龍、潑尼松、潑尼松龍或氫化可的松。 The medicinal composition for reducing skin diseases according to item 27 of the scope of patent application, wherein the steroid includes dexamethasone, flume, methasone, betamethasone, triamcinolone, prednisone, prednisone or Hydrocortisone. 如申請專利範圍第27項所述之減緩皮膚疾病之醫藥組成物，其中該醫藥組成物為局部給藥劑型或全身給藥劑型。 The medical composition for reducing skin diseases according to item 27 of the scope of application for a patent, wherein the pharmaceutical composition is a local administration form or a systemic administration form. 如申請專利範圍第27項所述之減緩皮膚疾病之醫藥組成物，其中該醫藥組成物為局部給藥劑型，其中該局部給藥劑型包括軟膏、乳劑、液劑或凝膠。 The medicinal composition for reducing skin diseases according to item 27 of the application, wherein the medicinal composition is a topical dosage form, and the topical dosage form includes an ointment, an emulsion, a liquid, or a gel.
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