WO2016078609A1 - 左旋沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡中的应用 - Google Patents

左旋沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡中的应用 Download PDF

Info

Publication number
WO2016078609A1
WO2016078609A1 PCT/CN2015/095101 CN2015095101W WO2016078609A1 WO 2016078609 A1 WO2016078609 A1 WO 2016078609A1 CN 2015095101 W CN2015095101 W CN 2015095101W WO 2016078609 A1 WO2016078609 A1 WO 2016078609A1
Authority
WO
WIPO (PCT)
Prior art keywords
salbutamol
skin
salt
sulfate
group
Prior art date
Application number
PCT/CN2015/095101
Other languages
English (en)
French (fr)
Inventor
徐玲
谭以知
谭律雅
Original Assignee
苏州君宁新药开发中心有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 苏州君宁新药开发中心有限公司 filed Critical 苏州君宁新药开发中心有限公司
Priority to AU2015349153A priority Critical patent/AU2015349153B2/en
Publication of WO2016078609A1 publication Critical patent/WO2016078609A1/zh

Links

Images

Classifications

    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone

Definitions

  • the present invention relates to a medicament, in particular to a pharmaceutical preparation for the treatment of skin damage, ulceration and delayed healing caused by wounds, burns, acne, tumors, diabetes and the like, as an external preparation of levorotatory (R) albuterol salt and a combination thereof.
  • a pharmaceutical preparation for the treatment of skin damage, ulceration and delayed healing caused by wounds, burns, acne, tumors, diabetes and the like as an external preparation of levorotatory (R) albuterol salt and a combination thereof.
  • the racemic albuterol is a beta receptor agonist containing a chiral center, an enantiomer with opposite optical properties - the R (left-handed) configuration of salbutamol and the S (dextrorotatory) configuration of salbutamol.
  • L-salbutamol has a variety of anti-inflammatory effects, can stimulate T cells under the action of plant lectin, inhibit the proliferation and secretion of IL-2 and interferon gamma.
  • the existing literature (CN 101203214B) has reported that L-R-salbutamol can treat cutaneous lupus erythematosus, and treatment with DEL (disc lupus erythematosus) and SCLE (subacute lupus erythematosus) shows a significant reduction in the leptin of the l-salbutamol group compared with the placebo group. . It can also treat other connective tissue diseases. L-Salbutamol may inhibit such abnormal autonomic responses by stimulating T cells.
  • Lupus and connective tissue diseases are autoimmune diseases. It is often associated with the body's own humoral antibodies or T cell abnormalities, and does not involve trauma and infection. However, the existing literature does not report whether L-salbutamol inhibits skin tissue ulcers and/or combined bacterial infections caused by external trauma, burns, burns, tumors, diabetes or infections, as well as wound wounds that can promote wounds caused by the above-mentioned causes. Heal.
  • autoimmune diseases such as lupus erythematosus and connective tissue diseases
  • external wounds, burns, burns, tumors, diabetes, or infections cause skin tissue ulcers and/or combined bacterial infections.
  • Skin ulcer is a localized defect or ulceration of the skin or mucosal surface tissue. The surface is often covered with pus, necrotic tissue or suede. After the scar, it can be caused by infection, trauma, nodules or tumor rupture. Its size, shape, depth, development process, etc. are also inconsistent.
  • chronic skin ulcers are common and frequently-occurring diseases with long course and difficult to cure.
  • the cause of the disease may be trauma, burns, burns, hemorrhoids, or may be co-infection, eczema, diabetes and cancerous cancer, or a combination of the above factors.
  • L-R-salbutamol (sulfate) has the following structure:
  • L-(R)-salbutamol or a pharmaceutically acceptable salt thereof in the present invention, includes a salt formed with a usual pharmaceutically acceptable organic or inorganic acid, including a sulfate or hydrogen sulfate, a hydrochloride, a hydrobromide salt. , dihydrogen phosphate, methanesulfonate, bromide, acetate, oxalate, maleate, fumarate, succinate, 2-naphthyl sulfate, gluconate, Molybdate, tartrate, lactate, etc., pyruvate, isethionate, besylate, p-toluenesulfonate, and the like.
  • a salt formed with a usual pharmaceutically acceptable organic or inorganic acid including a sulfate or hydrogen sulfate, a hydrochloride, a hydrobromide salt.
  • L-R-salbutamol can also be prepared as an external preparation such as a topical ointment, spray, patch, powder, granule or the like, or a suppository or ointment for use in a body cavity, and an injection or a variety of sustained-release agents for the skin muscle.
  • an external preparation such as a topical ointment, spray, patch, powder, granule or the like, or a suppository or ointment for use in a body cavity, and an injection or a variety of sustained-release agents for the skin muscle.
  • the invention also encompasses a novel combination of use with hormonal drugs.
  • L-(R)-salbutamol and a pharmaceutically acceptable salt thereof can be used in combination with various corticosteroids, and can be prepared in various ratios to prepare the above-mentioned various preparations for external use for treating wounds, burns, burns, tumors.
  • corticosteroids include, for example, budesonide, ciclesonide, beclomethasone dipropionate, mometasone furoate, flunisolide, fluticasone propionate, triamcinolone acetonide, fluticasone, and the like, and physiologically An acceptable salt or solvent.
  • the invention also encompasses a novel combination of anti-inflammatory and immunomodulatory agents.
  • a therapeutic amount of L-R-salbutamol and a pharmaceutically acceptable salt thereof with an anti-inflammatory or immunomodulatory agent such as an interleukin receptor antagonist, a leukocyte stimulating factor, a tumor necrosis factor (TNF) antibody, an interferon, an integrin, etc. Used in combination.
  • an anti-inflammatory or immunomodulatory agent such as an interleukin receptor antagonist, a leukocyte stimulating factor, a tumor necrosis factor (TNF) antibody, an interferon, an integrin, etc. Used in combination.
  • the invention also includes a novel external antibiotic and other skin wound treatment chemicals, biological drugs or botanical drugs, such as ofloxacin or levofloxacin, amoxicillin, erythromycin, epidermal growth factor, etc. Combination use of drugs.
  • the combination treatment of the above combination preparation can be prepared into an external preparation such as a plaster, a patch, a spray, a powder, a granule or a suppository in a body cavity or various sustained release agents.
  • an external preparation such as a plaster, a patch, a spray, a powder, a granule or a suppository in a body cavity or various sustained release agents.
  • Combinations may be by simultaneous, sequential, or separate modes of administration to increase the therapeutic index or to provide a positive synergistic effect of the drug.
  • the amount of the above anti-inflammatory agent can be adjusted depending on the symptoms and age and the therapeutic target of the main drug.
  • the preparation method of L-salbutamol cream is as follows: Preparation of hydrophobic phase: accurately weigh (by volume) 5% petrolatum, 10% paraffin oil, 5% gelatin, 6% glyceryl monostearate, plus 0.5% Tween 80 (26.5% in total), heated to 70 ° C. Preparation of hydrophilic phase: Accurately weigh (by volume) 0.5% L-salbutamol sulfate, 5% propylene glycol, 0.5% benzyl alcohol, and add water to 73.5%. Heat to 70 ° C. The two phases were mixed (100%) and the mixture was cooled with stirring, which was a L-salbutamolol paste. The ratio of L-salbutamol and excipients can also be adjusted according to requirements, such as from 0.01% to 99%. Salbutamol.
  • mice weighing 25-29 g were randomly assigned to four experimental groups A, B, C, and D, 15 in each group, which caused an acute trauma model in the hair removal area of the back skin of the mouse.
  • a full-thickness skin resection is performed, resulting in a round hole of 8 mm in diameter (or two incisions, one on the back and one on the buttocks). They are kept in separate cages.
  • the four groups A, B, C and D were respectively applied with homemade L-salbutamol ointment, blank adjuvant and positive control drug (ofloxacin).
  • Mode of administration once daily (extension to 2 to 3 mm, thickness of about 0.5 mm).
  • the morphological changes of the wound were observed every day, the wound diameter was photographed and measured, and the wound scarring time and healing time were recorded.
  • the wound was healed with the wound closed, the surface was dry, the eschar was detached, and the recovery was normal, and the healing time was recorded.
  • the whole skin of the wound with normal surrounding tissue was taken every 5 days, fixed in 10% formalin, paraffin sections were prepared, HE staining, histopathological changes were observed under light microscope, and the growth of granulation tissue and re-epithelialization were observed. Variety.
  • Area calculation method Aseptic film trace area, or localized wound area measured by transparent sulfuric acid paper.
  • the wound area plane measurement method
  • Percentage of wound healing: healing rate original face - now wound / original face.
  • the wound area was analyzed by one-way repeated measurement data analysis.
  • mice After several days of observation, it was found that the percentage of wound healing in the mice was 85.7% in the L-salbutamol group, 84.5% in the positive control group, and 48.5% in the blank adjuvant group. At the same time period, the healing area of the mice in the drug-administered group was significantly larger than that in the blank adjuvant mice. See the comparison of the effect of L-salvadine sulfate ointment on skin wound healing in mice.
  • mice weighing 26-28 g were randomly assigned to two experimental groups, A and B, each group of 5, which caused an acute trauma model in the hair removal area of the back skin of the mouse, and a full-thickness skin with a circular puncher. Excised, resulting in a circular hole with a diameter of 8 mm. They are kept in separate cages.
  • a and B groups were separately applied with homemade L-salbutamol ointment and levo-sulphate and levofloxacin compound ointment. Mode of administration: once daily (extension to 2 to 3 mm, thickness of about 0.5 mm).
  • mice After several days of observation, it was found that the percentage of wound healing in mice was 88% in the L-salbutamol group and 90% in the compound group. At the same time, the L-Salbutamol combination group was small. The healing area of the rats was significantly greater than that of the L-salbutamol group.

Landscapes

  • Health & Medical Sciences (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

本发明提供左旋（R）沙丁胺醇的药用盐或其药物制剂，及其在制备用于治疗因创伤、褥疮、肿瘤、糖尿病或合并感染等导致的皮肤溃疡、损伤、化脓和延迟愈合等疾病的药物中的用途。所述药物制剂包含左旋沙丁胺醇的药用盐，或左旋沙丁胺醇的药用盐和激素、抗生素或抗炎药物。

Description

左旋沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡中的应用 技术领域
本发明涉及药物，具体涉及左旋(R)沙丁胺醇药盐及其组合的外用制剂，在治疗因创伤、烧伤、褥疮、肿瘤、糖尿病等原因引起的皮肤损伤、溃疡和延迟愈合中的药物应用。
背景技术：
消旋体沙丁胺醇是含有一个手性中心的β受体激动剂，具有相反旋光特性的对映异构体――R(左旋)构型沙丁胺醇和S(右旋)构型沙丁胺醇。药理研究发现：R构型沙丁胺醇和消旋体沙丁胺醇能够缓和肺部气道对一些致痉挛剂引起的的反应，即促进气管平滑机舒张，而S构型沙丁胺醇不仅不能舒张气管平滑肌而且在某些时候还会加剧支气管收缩；通过对人支气管离体实验发现，S构型沙丁胺醇能刺激肥大细胞加速由组胺和白细胞介导素4(LTC4)引起的收缩的可能性，S构型沙丁胺醇还会加剧嗜曙红细胞分泌嗜曙红过氧化酶。另一方面，研究表明左旋沙丁胺醇具有多种抗炎作用，可以在植物凝集素的作用下刺激T细胞，抑制IL-2和干扰素γ的增殖和分泌。现有文献(CN 101203214B)已经报道左旋R沙丁胺醇可以治疗皮肤红斑狼疮症，DEL(盘状红斑狼疮)和SCLE(亚急性红斑狼疮)的治疗显示，给左旋沙丁胺醇组比给安慰剂组硬块明显减少。同时可以治疗其它结缔组织疾病。左旋沙丁胺醇则可能通过刺激T细胞，抑制这类异常自体反应。
红斑狼疮和结缔组织疾病属于自身免疫性疾病。往往与机体自身的体液性抗体或T细胞异常反应有关，不涉及创伤和感染。然而现有文献并未报道左旋沙丁胺醇是否以抑制由于外部创伤、烧伤、烫伤、肿瘤、糖尿病或感染等引起的皮肤组织溃疡和(或合并)细菌性感染，以及可以促进上述原因创伤导致的创面伤口愈合。
发明内容：
与红斑狼疮和结缔组织疾病等自身免疫疾病不同，外部创伤、烧伤、烫伤、肿瘤、糖尿病或感染等引起皮肤组织溃疡和(或合并)细菌性感染。皮肤溃疡是皮肤或黏膜表面组织的局限性缺损、溃烂，其表面常覆盖有脓液、坏死组织或痂皮，愈后遗有瘢痕，可由感染、外伤、结节或肿瘤的破溃等所致，其大小、形态、深浅、发展过程等也不一致。常合并慢性感染，创口经久不愈。慢性皮肤溃疡是常见病、多发病，病程长、难以治愈。其致病原因可能是外伤、烧伤、烫伤、褥疮、也可能是合并感染、湿疹、糖尿病和肿瘤癌变，或上述因素的合并出现。
本发明意外的发现，使用左旋R沙丁胺醇的皮肤外用制剂可以被应用于治疗组织创伤和 (或合并)细菌性感染引起的上述皮肤溃疡，促进组织溃疡创面的恢复。从而促进伤口的愈合。左旋R沙丁胺醇(硫酸盐)具有以下结构：
Figure PCTCN2015095101-appb-000001
本发明中左旋(R)沙丁胺醇或其药学上可接受的盐，包括与通常的药学上可接受的有机或无机酸形成的盐，包括硫酸盐或硫酸氢盐、盐酸盐、氢溴酸盐、磷酸二氢盐、甲基磺酸盐、溴化盐、醋酸盐、草酸盐、马来酸盐、富马酸盐、琥珀酸盐、2-萘基硫酸盐、葡糖酸盐、拧檬酸盐、酒石酸盐、乳酸盐等、丙酮酸盐、羟乙基磺酸盐、苯磺酸盐、对甲苯磺酸盐等。
左旋R沙丁胺醇还可以制备成外用的膏剂、喷剂、贴剂、粉剂、颗粒剂等外用剂型或用体腔的栓剂、膏剂，以及于皮表肌肉的注射剂或各类缓释剂。
本发明还包括一种全新的与激素类药物的组合使用。本发明中左旋(R)沙丁胺醇以及它药学上可接受的盐，可以和各类皮质类固醇联合使用，以不同比例组合，制成上述各类制剂，外用用于治疗由于创伤、烧伤、烫伤、肿瘤、湿疹、糖尿病或感染等引起的皮肤组织溃疡和(或合并)细菌性感染，以及促进上述原因创伤导致的创面伤口愈合。发挥相加或协同的治疗效果。上述皮质类固醇包括：如布地奈德、环索奈德、二丙酸倍氯米松、糠酸莫米松、氟尼缩松、氟替卡松丙酸酯、曲安奈德、、氟替卡松、等以及它们的生理学上可接受的盐或溶剂。
本发明还包括一种全新的与抗炎和免疫调节剂药物的组合使用。即用治疗量的左旋R沙丁胺醇以及其药学上可接受的盐与抗炎或免疫调节剂，如白介素受体拮抗剂、白细胞刺激因子、肿瘤坏死因子(TNF)抗体、干扰素及整合素等等组合使用。
本发明还包括一种全新的与抗生素类药物如氧氟沙星或左氧氟沙星、阿莫西林、红霉素等常用的外用抗生素和其它皮肤创伤治疗化学药、生物药或植物药，表皮生长因子等药物的组合使用。
上述组合制剂组合治疗可以制备成外用制剂，如膏剂、贴剂、喷剂、粉剂、颗粒剂或体腔内的栓剂或各类缓释剂。外用或体腔内使用用于治疗由于创伤、烧伤、烫伤、肿瘤、湿疹、糖尿病或感染等引起的皮肤组织溃疡和(或合并)细菌性感染，以及促进上述原因创伤导致的创面伤口愈合。发挥相加或协同的治疗效果。
组合可以是通过同时的、续贯的、或分别的给药方式，从而提高治疗指数或起到药物的正向协同作用。上述抗炎药剂的用量范围可根据症状和年龄以及主药的治疗目标加以调整。
本发明的特征和优点在下文的详细说明中显而易见。然而，应理解的是，该详细说明和这些具体实施例以及同时给出的本发明的实施方式仅作说明使用，因为本领域技术人员根据所述详细说明很容易发现本发明的精神和范围内的各种变更和修改。
附图说明
图1左旋硫酸沙丁胺醇膏剂对小鼠皮肤创伤愈合的效果比较
实施例1：
左旋沙丁胺醇乳膏剂的制备
左旋沙丁胺醇乳膏剂的制备方法如下：制备疏水相：准确称量(按体积)5％的矿脂，10％的石蜡油，5％的明胶，6％单硬脂酸甘油酯、加0.5％的Tween80(共26.5％)，加热至70℃。制备亲水相：准确称量(按体积)0.5％左旋沙丁胺醇硫酸盐，5％丙二醇、0.5％苯甲醇，加水至73.5％。加热至70℃。两相混合(100％)，在搅拌下冷却该混合物，即为左旋沙丁胺醇膏剂。左旋沙丁胺醇和辅料的比例也可以根据需求而调整，比如从0.01％－99％.沙丁胺醇。
实施例2:
左旋硫酸沙丁胺醇膏剂对小鼠皮肤创伤的实验研究
将60只体重为25-29g的KM小鼠随机分配到A、B、C、D四个实验组，每组15只，在小鼠背部皮肤脱毛区造成急性创伤模型，用圆形打孔器做全层皮肤切除，造成直径为8mm的圆孔(或者两个切口，一个在背部，一个在臀部)。单只分笼饲养。A、B、C、D四组分别涂抹自制的左旋沙丁胺醇软膏、空白辅料和阳性对照药物(氧氟沙星)。给药方式：每天给药一次(外延至2～3mm，厚度约0.5mm)。
每天观察创面形态变化，照相并测量创面直径，记录创面结痂时间和愈合时间。以创面封闭、表面干燥、焦痂脱落、恢复正常为愈合，并记录愈合时间。每5天取附带周围正常组织的创面全层皮肤，经10％福尔马林固定，制备石蜡切片，HE染色，在光镜下观察组织病理改变，重点观察创面肉芽组织生长及再上皮化的变化。
面积计算方法：无菌薄膜描记面积，或用透明硫酸纸描记法测局部创面面积。用image pro图像处理软件计算创口面积(平面测量法)。创面愈合百分比：愈合率＝原创面-现创面/原创面。创面面积做单因素重复测量数据方差分析。
结果：经过数八天的观察，可以发现，小鼠创伤面积愈合的百分比，在给左旋沙丁胺醇组小鼠为85.7％，阳性对照药组为84.5％，而空白辅料组为48.5％。在同一时间段，给药组小鼠的愈合面积明显大于空白辅料小鼠。见附图左旋硫酸沙丁胺醇膏剂对小鼠皮肤创伤愈合的效果比较。
实施例3:
左旋硫酸沙丁胺醇和左氧氟沙星复方软膏剂对小鼠皮肤创伤的实验研究
将10只体重为26-28g的KM小鼠随机分配到A、B两个实验组，每组5只，在小鼠背部皮肤脱毛区造成急性创伤模型，用圆形打孔器做全层皮肤切除，造成直径为8mm的圆孔。单只分笼饲养。A、B两组分别涂抹自制的左旋沙丁胺醇软膏和左旋硫酸沙丁胺醇及左氧氟沙星复方软膏。给药方式：每天给药一次(外延至2～3mm，厚度约0.5mm)。
按前述(实例2)方法观察和计算创口面积(平面测量法)和创面愈合百分比。
结果：经过数八天的观察，可以发现，小鼠创伤面积愈合的百分比，在给左旋沙丁胺醇组小鼠为88％，复方药组为90％，在同一时间段，给左旋沙丁胺醇复方药组小鼠的愈合面积明显大于左旋沙丁胺醇组小鼠。
以上所述，仅是本发明的说明实施例，并非对本发明作任何形式上的限制，任何熟悉本专业的技术人员，在不脱离本发明技术方案范围内，当可利用上述揭示的方法及技术内容作出些许的更动或修饰为等同变化的等效实施例，但凡是依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰，均仍属于本发明技术方案的范围内。

Claims (15)

  1. 左旋沙丁胺醇药盐或其组合制剂，在制备用于治疗皮肤及粘膜创伤、溃疡和创面延迟愈合等疾病的药物中的应用。
  2. 根据权利要求1所述的应用，其特征在于，所述药盐包括硫酸盐或硫酸氢盐、盐酸盐、氢溴酸盐、磷酸二氢盐、甲基磺酸盐、溴化盐、醋酸盐、草酸盐、马来酸盐、富马酸盐、琥珀酸盐、2-萘基硫酸盐、葡糖酸盐、拧檬酸盐、酒石酸盐、乳酸盐等、丙酮酸盐、羟乙基磺酸盐、苯磺酸盐、对甲苯磺酸盐等。
  3. 根据权利要求1或2所述的应用，其特征在于，所述的组合制剂包含左旋沙丁胺醇药盐以及皮质类固醇，所述皮质类固醇选自布地奈德、环索奈德、二丙酸倍氯米松、糠酸莫米松、氟尼缩松、氟替卡松丙酸酯、曲安奈德、氟替卡松等以及它们的生理学上可接受的盐或溶剂。
  4. 根据权利要求1或2所述的应用，其特征在于，所述的组合制剂包含左旋沙丁胺醇药盐以及抗炎或免疫调节剂，所述抗炎或免疫调节剂选自白介素受体拮抗剂、白细胞刺激因子、肿瘤坏死因子(TNF)抗体、干扰素及整合素等。
  5. 根据权利要求1或2所述的应用，其特征在于，所述的组合制剂包含左旋沙丁胺醇药盐以及抗生素类药物，所述抗生素类药物选自氧氟沙星、左氧氟沙星、阿莫西林、或红霉素等常用的外用抗生素和其它皮肤创伤治疗化学药、生物药或植物药，表皮生长因子等药物。
  6. 根据前述任一权利要求所述的应用，其特征在于，所述左旋沙丁胺醇药盐或其组合制剂为外用膏剂、贴剂、擦剂、喷剂、粉剂、颗粒剂、滴剂，或体腔内的栓剂，或各类缓释剂。
  7. 根据权利要求1或2所述的应用，其特征在于，所述的皮肤溃疡和创伤疾病为皮肤或黏膜或角膜表面组织的限局性缺损、充血、溃疡，溃烂其表面常覆盖有脓液、坏死组织或痂皮和不愈合创面。
  8. 根据权利要求1或2所述的应用，其特征在于，所述的皮肤溃疡和创伤疾病的致病原因为外伤、烧伤、烫伤、褥疮、也可能是感染、湿疹、糖尿病和组织癌变，或上述因素的合并出现。
  9. 一种用于治疗皮肤及粘膜创伤、溃疡和创面延迟愈合等疾病的药物制剂，其特征在于，包含左旋沙丁胺醇药盐。
  10. 根据权利要求9所述的药物制剂，其特征在于，所述左旋沙丁胺醇药盐包括硫酸盐或硫酸氢盐、盐酸盐、氢溴酸盐、磷酸二氢盐、甲基磺酸盐、溴化盐、醋酸盐、草酸盐、马来酸盐、富马酸盐、琥珀酸盐、2-萘基硫酸盐、葡糖酸盐、拧檬酸盐、酒石酸盐、乳酸盐等、丙酮酸盐、羟乙基磺酸盐、苯磺酸盐、对甲苯磺酸盐等。
  11. 根据权利要求9或10所述的药物制剂，其特征在于，还包含下列物质：
    皮质类固醇，选自布地奈德、环索奈德、二丙酸倍氯米松、糠酸莫米松、氟尼缩松、氟替卡松丙酸酯、曲安奈德、氟替卡松、等以及它们的生理学上可接受的盐或溶剂；或者
    抗炎或免疫调节剂，选自白介素受体拮抗剂、白细胞刺激因子、肿瘤坏死因子(TNF)抗体、干扰素及整合素等；或者
    抗生素类药物，选自氧氟沙星、左氧氟沙星、阿莫西林、或红霉素等常用的外用抗生素和其它皮肤创伤治疗化学药、生物药或植物药，表皮生长因子等。
  12. 根据权利要求9-11任一所述的药物制剂，其特征在于，所述药物制剂为外用膏剂、贴剂、擦剂、喷剂、粉剂、颗粒剂、滴剂，或体腔内的栓剂，或各类缓释剂。
  13. 一种治疗皮肤及粘膜创伤、溃疡和创面延迟愈合等疾病的方法，包括使用左旋沙丁胺醇药盐或其组合制剂。
  14. 根据权利要求13所述的方法，其特征在于，所述组合制剂包含左旋沙丁胺醇药盐以及下列物质：
    皮质类固醇，选自布地奈德、环索奈德、二丙酸倍氯米松、糠酸莫米松、氟尼缩松、氟替卡松丙酸酯、曲安奈德、氟替卡松、等以及它们的生理学上可接受的盐或溶剂；或者
    抗炎或免疫调节剂，选自白介素受体拮抗剂、白细胞刺激因子、肿瘤坏死因子(TNF)抗体、干扰素及整合素等；或者
    抗生素类药物，选自氧氟沙星、左氧氟沙星、阿莫西林、或红霉素等常用的外用抗生素和其它皮肤创伤治疗化学药、生物药或植物药，表皮生长因子等。
  15. 根据权利要求13或14所述的方法，其特征在于，所述左旋沙丁胺醇药盐包括硫酸盐或硫酸氢盐、盐酸盐、氢溴酸盐、磷酸二氢盐、甲基磺酸盐、溴化盐、醋酸盐、草酸盐、马来酸盐、富马酸盐、琥珀酸盐、2-萘基硫酸盐、葡糖酸盐、拧檬酸盐、酒石酸盐、乳酸盐等、丙酮酸盐、羟乙基磺酸盐、苯磺酸盐、对甲苯磺酸盐等。
PCT/CN2015/095101 2014-11-21 2015-11-20 左旋沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡中的应用 WO2016078609A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2015349153A AU2015349153B2 (en) 2014-11-21 2015-11-20 Application of levalbuterol formulation in treatment of skin and mucous membrane traumatic ulcers

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201410667739.8 2014-11-21
CN201410667739.8A CN104606177B (zh) 2014-11-21 2014-11-21 左旋(r)沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡的药物应用

Publications (1)

Publication Number Publication Date
WO2016078609A1 true WO2016078609A1 (zh) 2016-05-26

Family

ID=53141001

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2015/095101 WO2016078609A1 (zh) 2014-11-21 2015-11-20 左旋沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡中的应用

Country Status (3)

Country Link
CN (1) CN104606177B (zh)
AU (1) AU2015349153B2 (zh)
WO (1) WO2016078609A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104606177B (zh) * 2014-11-21 2018-02-02 苏州君宁新药开发中心有限公司 左旋(r)沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡的药物应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101378790A (zh) * 2006-01-31 2009-03-04 大卫·瓦尚 用于促进多细胞生物的组织愈合的组合物和方法
CN104606177A (zh) * 2014-11-21 2015-05-13 苏州君宁新药开发中心有限公司 左旋(r)沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡的药物应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE602006015387D1 (de) * 2005-04-13 2010-08-26 Astion Dev As Beta-2 Adrenoceptor Agonisten zur Behandlung von Bindegewebserkrankungen der Haut
GB0805535D0 (en) * 2008-03-27 2008-04-30 Univ Leicester Scar prevention
GB2513297A (en) * 2013-03-08 2014-10-29 Univ Leicester Methods

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101378790A (zh) * 2006-01-31 2009-03-04 大卫·瓦尚 用于促进多细胞生物的组织愈合的组合物和方法
CN104606177A (zh) * 2014-11-21 2015-05-13 苏州君宁新药开发中心有限公司 左旋(r)沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡的药物应用

Also Published As

Publication number Publication date
AU2015349153A1 (en) 2017-07-13
AU2015349153B2 (en) 2019-03-21
CN104606177A (zh) 2015-05-13
CN104606177B (zh) 2018-02-02

Similar Documents

Publication Publication Date Title
US11975005B2 (en) Treatment of respiratory diseases
US20100152304A1 (en) Pharmaceutical composition comprising periplaneta americana or its ethanol extract and a method of using the same for treating inflammations
WO2019024758A1 (zh) 一种糖苷类化合物在制备用于治疗肝纤维化药物中的应用
EA029649B1 (ru) Гель на основе полифенолов гранатовой кожуры для лечения воспалительных заболеваний в гинекологии и способ его приготовления
CN105250696A (zh) 一种促进皮肤伤口愈合的中药凝胶剂及其制备方法
EP3320901A1 (en) Application of dimethylamino micheliolide
WO2016078609A1 (zh) 左旋沙丁胺醇制剂在治疗皮肤及粘膜创伤溃疡中的应用
CN109223860A (zh) 一种复方五行草喷剂
CN116196323B (zh) 香蒲新苷在制备降尿酸和/或治疗肾损伤药物中的应用
WO2020143744A1 (en) New formulations containing leukotriene receptor antagonists
TW201513894A (zh) 含埃克替尼的皮膚外用藥物組合物及其應用
JP7335954B2 (ja) 白頭翁サポニンｂ４の抗急性痛風性関節炎の医薬における用途
Halim et al. A comparison study on the effectiveness of local honey and salicylate gel for treatment of minor recurrent aphtous stomatitis
CN113613640A (zh) 肾上腺素能β2受体激动剂R-对映体在治疗炎症性肠病及其肠外疾病的新应用
CN110652510B (zh) 中乌宁在制备防治肾纤维化药物中的应用
JP2022531154A (ja) 炎症により引き起こされる自己免疫性皮膚疾患を治療するための化合物及びその使用
CN105233258A (zh) 一种祛痘的组合物
RU2710541C1 (ru) Способ лечения ангулярного хейлита, возникшего вследствие дефицита рибофлавина
WO2024077977A1 (zh) 紫草酸在制备治疗糖尿病溃疡药物中的应用
CN104491462B (zh) 一种治疗烫伤的药物组合物
CN114984056B (zh) 一种治疗克罗恩病的天然产物提取物及其应用
WO2019104587A1 (zh) 一种药物组合物及其用途
RU2539418C1 (ru) Способ лечения местно-распространенного рака орофарингеальной зоны
CN114366732B (zh) 泰妙菌素在制备用于治疗银屑病的药物中的应用
JP7462783B2 (ja) 口腔潰瘍の治療におけるアネモシドｂ４の医学的使用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15861216

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2015349153

Country of ref document: AU

Date of ref document: 20151120

Kind code of ref document: A

122 Ep: pct application non-entry in european phase

Ref document number: 15861216

Country of ref document: EP

Kind code of ref document: A1