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WO2016044999A1 - 绿原酸在制备治疗银屑病的药物中的用途 - Google Patents

绿原酸在制备治疗银屑病的药物中的用途 Download PDF

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Publication number
WO2016044999A1
WO2016044999A1 PCT/CN2014/087211 CN2014087211W WO2016044999A1 WO 2016044999 A1 WO2016044999 A1 WO 2016044999A1 CN 2014087211 W CN2014087211 W CN 2014087211W WO 2016044999 A1 WO2016044999 A1 WO 2016044999A1
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psoriasis
chlorogenic acid
preparation
group
regard
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French (fr)
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张洁
朱丽娜
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Sichuan Jiuzhang Biotechnology Co Ltd
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Sichuan Jiuzhang Biotechnology Co Ltd
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Priority to PCT/CN2014/087211 priority Critical patent/WO2016044999A1/zh
Priority to EP14902765.8A priority patent/EP3199151B1/en
Priority to US15/513,401 priority patent/US9884036B2/en
Publication of WO2016044999A1 publication Critical patent/WO2016044999A1/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics

Definitions

  • the present invention relates to the use of chlorogenic acid for the preparation of a medicament for the treatment of psoriasis.
  • Psoriasis commonly known as “psoriasis”
  • psoriasis is a common and easily recurrent chronic inflammatory skin disease characterized by mica-like scaly, red membranous disease, and punctiform hemorrhage.
  • the incidence rate in China is about 0.123%.
  • the incidence of psoriasis is on the rise. It has obvious seasonality at the beginning, and it is winter and heavy in summer. It can be caused by both men and women. The current cause is unknown, and there is still no effective treatment.
  • Psoriasis is currently classified into type 4, psoriasis vulgaris, arthritic psoriasis, erythrodermic psoriasis, and pustular psoriasis, with more than 99% of psoriasis vulgaris.
  • Psoriasis vulgaris is common psoriasis, while the other three types are called special psoriasis.
  • psoriasis vulgaris is generally divided into 4 types: blood heat type (blood heat and wind dry type), blood deficiency type (blood deficiency and wind dry type), blood dry type, blood stasis type (stagnation) Skin type);
  • blood heat type blood heat and wind dry type
  • blood deficiency type blood deficiency and wind dry type
  • blood dry type blood stasis type (stagnation) Skin type
  • the pustular type is generally classified as sepsis type (damp heat type)
  • the erythroder type is venom type (blood heat poison type)
  • the joint type is cold type or Rheumatism and resistance.
  • the main clinical manifestations of psoriasis vulgaris are: white stalks, shiny film and spotted hemorrhage.
  • the main pathological manifestations are: parakeratosis.
  • a small abscess composed of neutrophils can be seen, and the granular layer becomes thin or disappears.
  • the spinous layer is thickened and the epidermis is prolonged.
  • the dermal papillary vessels are twisted and expanded, and the wall is slightly thickened. Mild to moderate inflammatory cell infiltration in the upper part of the dermis.
  • Psoriasis vulgaris is more common, accounting for more than 90%.
  • Pustular psoriasis is a type of condition that is more severe in psoriasis, with generalized psoriasis and localized psoriasis. Clinically, it is characterized by aseptic pustules of miliary size based on generalized erythema around the body, often accompanied by hyperthermia and elevated white blood cells and hypoproteinemia, and may even be life-threatening. This type is rare in clinical practice, accounting for 0.77% of patients with psoriasis.
  • the pathology of psoriasis is that the epidermal keratinocytes are not fully mature, the cells are filled with air, and the refracted light becomes the silvery white mica-like scales seen in the clinic; the dermal papillary swelling in the dermis protrudes into the epidermis and approaches the stratum corneum.
  • Scaling the scales can damage the nipple blood vessels and cause spotted bleeding.
  • Western medicine believes that the occurrence of psoriasis is mainly related to autoimmune, metabolic and endocrine dysfunction, and climate change, mood swings, infection, trauma and so on are predisposing factors.
  • pathogenesis of psoriasis is complex and has not yet been fully elucidated. Its pathogenesis can be roughly summarized as follows: on the basis of a certain genetic background, a variety of pathogenic factors stimulate the body's immune system to cause T The cell-based immune system is dysfunctional, and the inflammatory cells migrate to the epidermis and locally infiltrate, causing local inflammation and abnormal proliferation of keratinocytes, eventually leading to the pathological changes of psoriasis.
  • Psoriasis is a common chronic inflammatory skin disease with keratinocyte hyperplasia, inflammatory cell infiltration and neovascularization as the main pathological changes. It is a common and frequently-occurring disease in dermatology. The etiology of this disease is unknown and difficult to treat. It is still not completely eradicated. At present, Western medicine uses vitamin A acid and immunosuppressive agents to treat the disease. It has advantages in controlling psoriasis activities, but there are many adverse reactions and recurrence rate after drug withdrawal. Higher problems.
  • the technical solution of the present invention is to provide a new use of chlorogenic acid.
  • the medicament is prepared by using an effective amount of chlorogenic acid as an active ingredient, and adding a pharmaceutically acceptable auxiliary or auxiliary component.
  • the drug is a drug for treating psoriasis vulgaris and pustular psoriasis.
  • the pharmaceutical preparation contains 1 to 3000 mg of chlorogenic acid per preparation unit.
  • the medicinal preparation uses chlorogenic acid in a dose of 10 to 40 mg/kg.
  • the agent is an oral preparation, a topical preparation or an injection.
  • Psoriasis is an immunologically abnormal chronic inflammatory proliferative skin disease induced by multiple genetic factors and stimulated by multiple environmental factors.
  • the prevalence rate of natural population in the world is 0.1%-3%, and the prevalence rate in China The rate was 0.123% and the annual incidence was 0.1%.
  • the disease does not endanger human life, its course is long and stubborn and difficult to treat. In severe cases, it can cause disabling psoriatic arthritis, erythrodermic shoulder disease, and even affect the eyes, liver, kidney, and cardiovascular. Organs such as lungs, which seriously affect the quality of life of patients. Some patients may have psychological disorders such as shame, nervousness, anxiety, depression, etc.
  • Chlorogenic acid is a small molecule compound, which is a biological response modifier, focusing on overall regulation. It has a good effect on reconstituting the immune function and has no damage to liver and kidney. It can be used for a long time without causing side effects on the body. Effective, improve the quality of life of patients, has a significant effect on psoriasis, especially for psoriasis vulgaris and pustular psoriasis, so chlorogenic acid has a broad application prospects in the treatment of psoriasis.
  • Awei A capsule purchased from Chongqing Huabang Pharmaceutical Co., Ltd., batch number: 2013010 chlorogenic acid, provided by Sichuan Jiuzhang Biotechnology Co., Ltd., batch number: 1306015% Xindean raw material 100g, Hubei Kangbaotai Fine Chemical Co., Ltd., batch number 20130525 emulsion
  • the substrate is provided by the preparation room of West China Pharmaceutical College, Sichuan University.
  • the guinea pigs were started after 1 week of adaptive feeding.
  • the guinea pigs were depilated and randomly divided into blank group and experimental group. There were 12 blank groups and 48 experimental groups.
  • the experimental group was evenly applied to the dorsum of both sides of the guinea pig with 5% anti-analing agent.
  • the blank group was applied with a blank matrix, and the thickness of each application was about 1.0 mm, 4 times/d for 14 days, which caused pathological changes of psoriasis vulgaris. . After 14 days, 2 in the blank group and 4 in the experimental group were used for pathological examination.
  • guinea pig ear tissue had parakeratosis and hyperkeratosis, the granular layer became thin, the inflammatory cells infiltrated, the dermal vasodilatation, and the mastoid Prominent, suggesting successful modeling.
  • 44 guinea pigs in the remaining experimental group were divided into 4 groups according to the body mass and modeling conditions, which were model group, positive group, low dose chlorogenic acid group and high dose chlorogenic acid group. 11 only.
  • the blank group and the model group were given 0.9% sodium chloride solution; the positive drug control group was given 2.64 mg/kg of Avi A capsule suspension, the gastric perfusion amount was 1 mL/100 g each time, 2 times/d; the chlorogenic acid was low.
  • the dose group was intramuscularly administered with 20 mg/kg, and the high dose chlorogenic acid group was administered intramuscularly with 40 mg/kg, and the volume was 0.2 ml/10 g once daily.
  • Histopathological score assessment was performed according to the Baker method: 2.0 points for Munro small abscess in the stratum corneum; 0.5 point for excessive keratinization; 1.0 point for parakeratosis; 1.0 point for thinning or disappearance of granular layer; 1.0 point for acanthosis hypertrophy; Prolonged, basal layer undulating, according to the light, medium and heavy degrees of 0.5, 1.0, 1.5 points; dermal mononuclear and polymorphonuclear cell infiltration, according to light, medium and heavy degrees of 0.5, 1.0, 2.0 points; The mastoid protrusion was markedly 0.5 points; the superficial dermal vasodilator was 0.5 points.
  • the histological pathology of the positive group and the chlorogenic acid group was significantly improved.
  • the pathological sections of the ear of guinea pig are shown in Fig. 1 to Fig. 5.
  • the pathological changes of psoriasis in the guinea pig ear of each group are shown in Fig. 6.
  • Chlorogenic acid provided by Sichuan Jiuzhang Biotechnology Co., Ltd., batch number: 130601
  • Kunming mice were randomly divided into 3 groups. Blank control group: per day, about 0.5 ml of peanut oil was used for intragastric administration; chlorogenic acid high dose group (20 mg ⁇ kg -1 ), each mouse was intraperitoneally injected with 0.4 ml/20 g; chlorogenic acid low dose group (10 mg ⁇ kg - 1 ) Each mouse was intraperitoneally injected with 0.4 ml/20 g. Observation phase points: when not administered (day 0), days 1, 2, 4, and 6 after administration.
  • a 1 cm 2 sterile gelatin sponge was soaked in 0.75% zymosan A for 30 min, surgically placed in the peritoneal cavity of the mice, and normal feeding was given. At 24 hours after operation, 5 mice were sacrificed at the same time point, and the gelatin sponge was taken out and placed in 0.5 ml of cell eluate for 30 min at 37 ° C. The gelatin sponge was rinsed with 0.01 ml/L PBS 0.5 ml respectively.
  • the eluate was collected, centrifuged to a volume of 0.5 ml after passing through a 40 ⁇ m nylon mesh, and the above eluate was subjected to cell sorting and counting by an automatic blood cell meter to read the number of polymorphonuclear leukocytes (PMN).
  • PMN polymorphonuclear leukocytes
  • PMN plays an important role in the pathogenesis of pustular psoriasis. Pustular regression in patients with pustular psoriasis is accompanied by a significant decrease in PMN chemotactic activity. If the drug can inhibit the chemotactic activity of normal PMN, it indicates that the drug can treat pustular silver by inhibiting PMN chemotactic activity. The role of psoriasis.
  • chlorogenic acid can significantly inhibit the chemotactic activity of PMN in normal mice, and the inhibition effect of PMN chemotactic activity in mice with high dose of chlorogenic acid is stronger in the lower dose group.
  • Chlorogenic acid can inhibit the expression of PMN surface adhesion molecules in pustular psoriasis patients, and chlorogenic acid has a good effect in the treatment of pustular psoriasis.

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Abstract

绿原酸在制备治疗银屑病的药物中的用途。绿原酸是小分子化合物，为生物反应调节剂，着重于整体调节，对于重建免疫功能自稳状态有良好作用，且对肝肾无损害作用，可长期使用，对机体不产生毒副作用，安全有效，复发率低，提高患者的生活质量，对银屑病有显著的疗效，对寻常型银屑病、脓疽型银屑病作用尤为明显，故绿原酸治疗银屑病有广阔的应用前景。

Description

绿原酸在制备治疗银屑病的药物中的用途 技术领域
本发明涉及绿原酸在制备治疗银屑病的药物中的用途。
背景技术
银屑病俗称“牛皮癣”，是一种常见的并易复发的慢性炎症性皮肤病，以云母状鳞屑、红膜症、点状出血为临床特征，在我国的发病率约为0.123％。近年来,银屑病发病呈上升趋势，其初期有明显的季节性，呈冬重夏轻，无论男女老幼皆可发病，目前病因未明，尚缺乏有效的治疗方法。
银屑病目前分为4型，寻常型银屑病、关节病型银屑病、红皮病型银屑病和脓疱型银屑病，其中寻常型银屑病占99％以上。寻常型银屑病为普通型银屑病，而其他三型称为特殊型银屑病。根据历代中医名家经验总结,寻常型银屑病一般分为4型：即血热型(血热风燥型)，血虚型(血虚风燥型)，血燥型，血瘀型(瘀滞肌肤型)；特殊型银屑病中，脓疱型一般辨证为脓毒型(湿热蕴毒型)，红皮病型为毒热型(血热毒盛型)，关节型为寒湿型或风湿痹阻型。
寻常型银屑病的主要临床表现为：白色麟屑、发亮薄膜和点状出血。主要病理表现为：角化不全，在角层内或角层下，可见由中性粒细胞构成的小脓肿(Munro小脓肿)，颗粒层变薄或消失。棘层增厚，表皮突延长。真皮乳头部血管扭曲扩张，管壁轻度增厚。真皮上部轻度到中度炎症细胞浸润。寻常型银屑病较为常见，大约占90％以上。
脓疱型银屑病是银屑病中病情较为严重的一种类型,分泛发性银屑病及局限性银屑病。临床上以周身泛发红斑基础上粟粒大小的无菌性脓疱为特征，常伴有高热及白细胞升高和低蛋白血症，甚至可以危及生命。本型在临床上较少见，约占银屑病人的0.77％。
银屑病组织病理为表皮角质细胞不能完全成熟，细胞束之间充满空气，并折射光线成为临床上所见的银白色云母状鳞屑；真皮内的乳头水肿胀大突入表皮接近角质层，临床上搔刮鳞屑可损伤乳头血管而出现点状出血。西医认为，银屑病的发生主要与自身免疫、代谢及内分泌功能紊乱有关，而气候变化、情绪波动、感染、外伤等为诱发因素。
银屑病发病机制复杂，目前尚未完全得以阐明，其发病机制大致可以概括为：在一定遗传背景的基础上，多种致病因子刺激机体免疫系统引起以T 细胞为主的免疫系统功能紊乱，炎症细胞移行到表皮并在局部浸润，造成局部炎症和角质形成细胞异常增生，最终导致银屑病病理改变的发生。
银屑病是一种常见的以角质形成细胞过度增生、炎症细胞浸润和新生血管形成为主要病理改变的慢性炎症性皮肤病，为皮肤科常见病、多发病。本病病因不明，治疗困难，尚无法完全根除，目前西药多使用维A酸及免疫抑制剂治疗该病，其在控制银屑病活动方面具有优势，但存在不良反应多、停药后复发率高等问题。
发明内容
本发明的技术方案是提供了绿原酸的新用途。
本发明绿原酸在制备治疗银屑病的药物中的用途。
其中，所述的药物是以有效量的绿原酸为活性成分，加上药学上可接受的辅料或者辅助性成分制备而成的制剂。所述的药物是治疗寻常型银屑病、脓疱型银屑病的药物。
其中，所述的药物制剂中每制剂单位含有绿原酸1～3000mg。
其中，所述的药物制剂中绿原酸的使用剂量为10～40mg/kg。
其中，所述的药剂是口服制剂、外用制剂或者注射剂。
银屑病是一种由多基因遗传决定的、多环境因素刺激诱导的免疫异常性慢性炎症性增生性皮肤病，在世界范围内自然人群患病率为0.1％-3％，我国患病率为0.123％，年发病率为0.1％。尽管该病不危及人的生命，但其病程长且顽固难治，严重者可发生致残性银屑病性关节炎、红皮病型银肩病，甚至累及眼、肝脏、肾脏、心血管、肺等器官，从而严重影响患者的生活质量。有些患者可出现心理障碍如羞愧、紧张、焦虑、忧郁等，不愿参加社交活动，影响日常生活，给患者身体和心理带来极大的痛苦。由于该病反复发作，常需反复治疗，因而给患者及其家庭带来沉重的经济负担。目前银屑病无法治愈，传统的治疗除中药外多为免疫抑制剂及维A酸类药物，长期应用这些药物易产生依赖性及肝肾损害等严重的副作用。
绿原酸是小分子化合物，为生物反应调节剂，着重于整体调节，对于重建免疫功能自稳状态有良好作用，且对肝肾无损害作用，可长期使用，对机体不产生毒副作用，安全有效，提高患者的生活质量，对银屑病有显著的疗效，尤其对寻常型银屑病和脓疱型银屑病作用尤为明显，故绿原酸治疗银屑病有广阔的应用前景。
附图说明
图1空白组
图2模型组
图3阳性组
图4绿原酸低剂量组
图5绿原酸高剂量组
图6各组豚鼠耳部银屑病样病理变化Baker评分(注：与空白组比较，**P<0.01；与模型组比较，##P<0.01。)
具体实施方式
试验例1本发明绿原酸治疗银屑病的药效试验(寻常型银屑病模型)
实验研究：
1.材料
1)动物
雄性豚鼠，体质量350-400g，四川大学试验动物中心提供。动物级别：一级，许可证号：第10号。
2)药品与试剂
阿维A胶囊，购自重庆华邦制药股份有限公司，批号：2013010绿原酸，四川九章生物科技有限公司提供，批号：1306015％心得安原料100g，湖北康宝泰精细化工有限公司，批号20130525乳剂基质由四川大学华西药学院制剂室提供
2.实验方法
1)模型制备及分组
豚鼠60只，适应性饲养1周后开始实验，将豚鼠双耳去毛，随机分为空白组和实验组。空白组12只，实验组48只。实验组用5％心得安乳剂均匀涂于豚鼠双侧耳背，空白组涂抹空白基质，每次涂抹厚度约1.0mm，4次/d，共14天，使其产生寻常型银屑病样病理改变。14天后，空白组取2只、实验组取4只用于病理检测，结果显示豚鼠耳组织出现角化不全及角化过度，颗粒层变薄，炎细胞浸润，真皮浅层血管扩张，乳突突出，提示造模成功。将所剩实验组44只豚鼠根据体质量和造模情况用随机数字表法分为4个组，分别是模型组、阳性组、绿原酸低剂量组、绿原酸高剂量组，每组11只。
2)给药
空白组和模型组给予0.9％氯化钠溶液；阳性药对照组给予阿维A胶囊混悬剂2.25mg/kg，灌胃量均为每次1mL/100g，2次/d；绿原酸低剂量组肌肉注射给予20mg/kg，绿原酸高剂量组肌肉注射给予40mg/kg，容量为0.2ml/10g，1次/d。
3)取材及处理
给药14d后取材，腹腔注射12％水合氯醛，0.35mL/100g，麻醉后，腹主动脉取血处死，剪取豚鼠双耳组织，固定于10％甲醛溶液中。取豚鼠耳组 织，石蜡包埋，切片，常规HE染色，中性树胶封片。光学显微镜下观察耳部病理变化，在10×20视野下观察并拍照。参照Baker法进行组织病理积分评估：角质层有Munro小脓肿计2.0分；过度角化0.5分；角化不全1.0分；颗粒层变薄或消失计1.0分；棘层肥厚计1.0分；皮突延长、基底层迂曲起伏，根据轻、中、重程度分别计0.5、1.0、1.5分；真皮层单一核及多形核细胞浸润，根据轻、中、重程度分别计0.5、1.0、2.0分；乳突突出明显计0.5分；真皮浅层毛细血管扩张计0.5分。
4)对肝功肾功能的影响
处死豚鼠前，经腹腔静脉抽血，采用酶法检测尿素氮和肌酐，采用速率法检测谷丙转氨酶和谷草转氨酶。
3.统计学方法
所有数据均用SPSS 13.0统计软件处理，实验结果计量资料用x±s表示，以P<0.05为差异具有统计学意义。多样本均数比较采用方差分析。
4.结果
1)光镜观察结果显示，空白组角质层薄，呈网状交织，几乎无颗粒层清晰，约1-2层；棘层细胞3-5层；基底层为单层柱状细胞，表皮突平坦；真皮层未见浅层毛细管扩张，少量分布淋巴细胞。模型组可见角化过度，角化不全，颗粒层变薄或消失，棘层肥厚，真皮毛细血管扩张等现象，还可见真皮层有轻中度炎细胞浸润。给药后，阳性组和绿原酸组，其皮损组织病理有明显改善。豚鼠耳部的病理切片见图1-图5，各组豚鼠耳部银屑病病理变化Baker评分见图6。
统计结果显示，空白组、各个给药组与模型组相比，Baker评分数具有显著性差异(P<0.01)，提示造模成功，各个给药组对改善豚鼠银屑病样病变有效。阳性组与绿原酸高、低剂量组评分无显著性差异。绿原酸低剂量组评分优于高剂量组，量效关系不呈剂量依赖型。各个给药组光镜下观察可见过度角化和角化不全现象减轻，颗粒层增加，棘层变薄，炎性细胞浸润程度降低，提示绿原酸能够治疗银屑病。
2)对肝功肾功能的影响
单因素方差分析显示，阳性对照组尿素氮、血肌酐、谷丙转氨酶(ALT)、谷草转氨酶(AST)明显高于其他各组(P<0.05)，见表1。提示绿原酸对肝肾功能具有保护作用，安全性好。
表1绿原酸对豚鼠肝肾功的影响
Figure PCTCN2014087211-appb-000001
注：与空白组比较，*P<0.05。
试验例2本发明绿原酸治疗银屑病的药效试验(脓疱型银屑病)
实验研究：
1.材料
1)动物
昆明种小鼠，体质量18-22g，四川大学试验动物中心提供。动物级别：一级，许可证号：第10号。
2)药物
绿原酸，四川九章生物科技有限公司提供，批号：130601
2.实验方法
1)动物分组
昆明种小鼠随机均分为3组。空白对照组：根据体重每天用0.5ml左右的花生油灌胃；绿原酸高剂量组(20mg·kg-1)，各鼠腹腔注射0.4ml/20g；绿原酸低剂量组(10mg·kg-1)、各鼠腹腔注射0.4ml/20g。观察时相点：未给药时(0天)，给药后第1、2、4、6天。
2)实验方法
将一块1cm2的无菌明胶海绵在0.75％酵母聚糖A中浸泡30min后，手术置入小鼠的腹膜腔中，并给予正常喂饲。术后24小时，断颈处死同一时相点的5只小鼠，取出明胶海绵，分别置于0.5ml的细胞洗脱液中37℃孵育30min，以0.01mol/LPBS0.5ml分别漂洗明胶海绵3次，收集洗脱液，过40μm尼龙筛网后离心定容至0.5ml，以全自动血细胞仪对上述洗脱液进行细胞分类计数，读取多形核白细胞(PMN)的数量。
3.结果
绿原酸不同剂量组在不同时相点的PMN迁移数量的比较见表2。绿原酸不同剂量组间PMN迁移数量有显著性差异(P<0.01)，同组内各时间点PMN迁移数量也有显著性差异(P<0.01)。
表2绿原酸不同剂量组在不同时相点的PMN迁移数量(×109/L)
Figure PCTCN2014087211-appb-000002
4.结论
PMN在脓疱型银屑病的发病中具有十分重要的作用。脓疱型银屑病患者的脓疱消退的同时伴有PMN趋化活性的显著减低，如果药物能够抑制正常PMN的趋化活性，说明药物可通过抑制PMN趋化活性从而具有治疗脓疱型银屑病的作用。
上述实验结果表明，绿原酸可以显著抑制正常小鼠PMN的趋化活性，绿原酸高剂量组对小鼠PMN趋化活性的抑制作用较低剂量组更强。绿原酸可抑制脓疱型银屑病患者PMN表面黏附分子的表达，从而绿原酸在治疗脓疱型银屑病方面具有良好功效。

Claims (6)

  1. 绿原酸在制备治疗银屑病的药物中的用途。
  2. 根据权利要求1所述的用途，其特征在于：所述的药物是治疗寻常型银屑病、脓疱型银屑病的药物。
  3. 根据权利要求1或2所述的用途，其特征在于：所述的药物是以有效量的绿原酸为活性成分，加上药学上可接受的辅料或者辅助性成分制备而成的制剂。
  4. 根据权利要求3所述的用途，其特征在于：所述的药物制剂中每制剂单位含有绿原酸1～3000mg。
  5. 根据权利要求4所述的用途，其特征在于：所述的药物制剂中绿原酸的使用剂量为10～40mg/kg。
  6. 根据权利要求3-5任意一项所述的用途，其特征在于：所述的药剂是口服制剂、外用制剂或者注射剂。
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JP2007223948A (ja) * 2006-02-23 2007-09-06 Api Co Ltd 血管新生抑制剤
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