WO2004084915A1 - Utilisation de n-acetyl-d-aminoglycosamine dans le traitement d'inflammations non specifiques associees a des facteurs physiques ou chimiques - Google Patents

Utilisation de n-acetyl-d-aminoglycosamine dans le traitement d'inflammations non specifiques associees a des facteurs physiques ou chimiques Download PDF

Info

Publication number
WO2004084915A1
WO2004084915A1 PCT/CN2004/000280 CN2004000280W WO2004084915A1 WO 2004084915 A1 WO2004084915 A1 WO 2004084915A1 CN 2004000280 W CN2004000280 W CN 2004000280W WO 2004084915 A1 WO2004084915 A1 WO 2004084915A1
Authority
WO
WIPO (PCT)
Prior art keywords
physical
acetylglucosamine
test
treatment
chemical factors
Prior art date
Application number
PCT/CN2004/000280
Other languages
English (en)
French (fr)
Inventor
Qiwang Xu
Junkang Liu
Zetao Yuan
Original Assignee
Third Military Medical University, Chinese People's Liberation Army, P.R. Of China
Bio-Wave Institute Of Suzhou Hi-Tech New District Corporation, Ltd.
Beijing Sino-Hongkong Dafu Science & Technology Of Biowave Co., Ltd
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 Third Military Medical University, Chinese People's Liberation Army, P.R. Of China, Bio-Wave Institute Of Suzhou Hi-Tech New District Corporation, Ltd., Beijing Sino-Hongkong Dafu Science & Technology Of Biowave Co., Ltd filed Critical Third Military Medical University, Chinese People's Liberation Army, P.R. Of China
Priority to US10/551,258 priority Critical patent/US20070178161A1/en
Priority to JP2006504206A priority patent/JP2006521298A/ja
Priority to EP04723952A priority patent/EP1611894A4/en
Publication of WO2004084915A1 publication Critical patent/WO2004084915A1/zh

Links

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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • 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
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • N-acetylglucosamine in the treatment and control of non-specific inflammation caused by physicochemical factors
  • the present invention relates to the use of N-acetylglucosamine and its pharmaceutically acceptable salts in the treatment of non-specific inflammation and symptom control caused by physical and chemical factors, and N-acetylglucosamine and its pharmaceutically acceptable salts in the preparation of Application of medicines for treating non-specific inflammation and controlling symptoms caused by physical and chemical factors.
  • the common physical factors include burning, exposure, crushing, frostbite, blunt tears, etc.
  • the chemical factors are usually strong acid, alkali burns or lime burns.
  • the body can develop non-specific inflammation under the effect of the above factors. 5 It is expressed as local congestion, edema, secretion and exudation, increased pain, 9 and even skin damage and necrosis.
  • the mechanism of non-specific inflammation is that under normal circumstances, all levels of the body's life activities are coordinated with each other and proceed normally. When physical or chemical changes occur suddenly, they can directly damage the structure of tissue cells, such as fleas, and cause the cell structure to be destroyed or cause the environment of cells to deteriorate.
  • This biphasic change gives N-acetylglucosamine a random high-affinity interaction with body components such as cells and subcellular biomolecules, thereby stabilizing the configuration and conformation of these components and preventing the original Changes caused by adverse factors continue to expand.
  • N- acetyl glucosamine is a chemical reagent, one after another since the 1990s is for the treatment of periodontitis (W09102530A!), Microbial infections (WO9718790A 3), inflammatory bowel disease ( ), Corneal diseases (JP10287570A 2 ), prostatic hypertrophy (missing 51 articles 15) and other diseases, and beauty (JPS901370 ⁇ A 2 ) 3 ⁇ 4 shampoo preparations (JP2011505A 2 ) and so on. At present, no one has used it for the preparation of a pharmaceutical preparation for treating nonspecific inflammation and controlling symptoms caused by physicochemical factors.
  • N-acetylglucosamine and its pharmaceutically acceptable salts can quickly and effectively treat non-specific inflammation and control symptoms caused by physical and / or chemical factors, and prevent further expansion of damage, thereby completing the present invention invention.
  • N-acetylglucosamine and its pharmaceutically acceptable salts in the treatment of non-specific inflammation caused by physical and / or chemical factors.
  • Another object of the present invention is to provide the use of N-acetylglucosamine and a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of non-specific inflammation caused by physical and / or chemical factors.
  • Another object of the present invention is to provide treatment of non-specific causes caused by physical and chemical factors.
  • a method of heterosexual inflammation comprising administering to a patient a pharmaceutical composition comprising an effective amount of N-acetylglucosamine or a pharmaceutically acceptable salt thereof.
  • N-acetylglucosamine or a pharmaceutically acceptable salt thereof as an active ingredient, optionally combined with various pharmaceutical excipients or carriers known in the art, to prepare water.
  • Agent, liquor, ointment, powder or injection for treating and controlling non-specific inflammation caused by physical and / or chemical factors.
  • N-acetylglucosamine N-acetyl-D-glucosamine
  • molecular formula C 8 H 1S N0 6
  • structural formula (I) is represented as follows:
  • Examples of pharmaceutically acceptable salts of -acetyl-D-glucosamine that can be used in the present invention include, but are not limited to, those salts formed with inorganic acids, such as hydrochloride, hydrobromide, borate, phosphate , Sulfates, bisulfates and hydrogen phosphates, and those with organic acids such as citrate, benzoate, ascorbate, methyl sulfate, picrate, fumarate, malay Salt, malonate, succinate, tartrate, mesylate and glucose small phosphate.
  • inorganic acids such as hydrochloride, hydrobromide, borate, phosphate , Sulfates, bisulfates and hydrogen phosphates
  • organic acids such as citrate, benzoate, ascorbate, methyl sulfate, picrate, fumarate, malay Salt, malonate, succinate, tartrate, mesylate and glucose small phosphate.
  • the content of N-acetylglucosamine or a pharmaceutically acceptable salt thereof may generally be 0.1-10% by weight.
  • N-acetylglucosamine or a pharmaceutically acceptable salt thereof may be combined with various pharmaceutical excipients or carriers known in the art to prepare, for example, a water, liquor, cream, powder or injection form .
  • the pharmaceutical composition of the present invention can be administered by various routes, such as injection, oral, topical application, topical cleaning, or a combination thereof.
  • the active ingredient of the drug of the present invention N-acetylglucosamine or a pharmaceutically acceptable salt thereof
  • a solution or suspension For intramuscular or intravenous application, it can be diluted with diluents such as 0.9% physiological saline for injection, sterile water for injection or 0.5% lidocaine hydrochloride, and further diluted with 5% glucose solution or 0.9% physiological saline for injection.
  • diluents such as 0.9% physiological saline for injection, sterile water for injection or 0.5% lidocaine hydrochloride
  • 5% glucose solution or 0.9% physiological saline for injection for the preparation of a topical ointment
  • a topical ointment such as petrolatum may be used as an excipient 0
  • the present invention comprises N- acetylglucosamine or a pharmaceutically acceptable salt thereof pharmaceutical compositions may be administered in a single dose or multiple daily dose administration of a dose of the pharmaceutical composition of the present invention, ⁇ subject of administration depending on the age, condition , The symptoms to be treated and the way of administration. Generally, however, for an adult patient weighing about 75 kg, the pharmaceutical composition of the present invention is administered at a daily dose of 1 to 1000 g of stigma 5, preferably 10 to 1 g of sacron, based on the active ingredient.
  • N-acetylglucosamine or its pharmaceutically acceptable salt promotes cell redistribution and stabilizes lysosomal membranes in adverse environments by regulating biological waves, thereby treating and controlling Non-specific inflammation and prevent further expansion of damage.
  • the compound has almost no toxicity and overcomes many side effects brought by the use of drugs such as hormones in the treatment of non-specific inflammation.
  • Proteus mirabilis should meet the following biochemical response characteristics: kinetic (+), urease (+), lactose (-), glucose (+), H 2 S (-), phenylalanine deaminase (+ ).
  • LB medium Improved LB medium (composition: 1% tryptone, 0.5% yeast extract, 1% sodium chloride, 0.1% glucose, 0.002% TTC, PH7.2-7.4) D
  • Test sample A compound of formula (IX) 5 with a final concentration of 0 5% was added to a LIB plate to seed Proteus mirabilis in the same way, and cultured for 9 hours at 37 ° C.
  • Acute toxicology test including oral, intravenous and maximum dose test
  • Twenty Wistar rats were selected and randomly divided into two groups, the control group and the test group. Both groups used gauze distilled water to cover the heat, which caused burn models. The animals in the control group were not treated, and the animals in the test group were treated with "compound (1)" solid powder and applied locally. Results After 3 days, there were 8 scabs in the experimental group and only 2 scabs in the control group, with pus accumulation still under the scab. There was a significant difference in burn response between the two.
  • mice Thirty Kunming mice were randomly selected and randomly divided into 2 groups, that is, 10 in the control group and 20 in the test group. Both groups used a blunt tear method to cause nonspecific damage to the thigh muscles of the hind limbs of the mice after the iliac tear. It is manifested by the inability of the injured limb to flex and flex freely, local swelling, and pain (cannot touch).
  • the control group was provided with 10 mice normally, and the test group was given an N-acetylglucosamine aqueous solution with a drug concentration of 5% by weight. 10 mice were injected intraperitoneally and 10 were administered by local intramuscular injection. The injection volume was 1 liter. Results After 7 days of administration, the animal responses were different between the two groups.
  • N-acetylglucosamine A small amount of glucose and petroleum jelly are added together to make a paste, the concentration is 1 g / 10 g, and it is applied to the affected part. The dosage varies according to the size of the wound, and it is used continuously for 3 days. It can be seen that the facial abrasion wounds healed quickly and no scars were left on the face.
  • Example 6 Frostbite Treatment Test
  • test group Twenty patients with varying degrees of frostbite were observed among the trainees.
  • the test group was administered locally with a 10% by weight aqueous solution of N-acetylglucosamine. According to symptoms and individual conditions, the dosages were 1 to 10 liters per day Not waiting. The test group showed early recovery, and then reduced inflammation and swelling. In the other 10 control groups, the symptoms persisted, and the inflammatory manifestations of redness, swelling and pain were obvious.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Toxicology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)

Description

N -乙酰氨基葡萄糖在治疗和控制物理 化学因素致非特异性炎症中的应用 技术领域
本发明涉及 N-乙酰氨基葡萄糖和其药物可接受的盐在治疗 物理、 化学因素引起的非特异性炎症及控制症状中的应用， 及 N- 乙酰氨基葡萄糖和其药物可接受的盐在制备用于治疗物理、 化学 因素引起的非特异性炎症及控制症状的药物中的应用。
背景技术
引起非特异性炎症的因素种类多样， 其中常见的物理因素涉 及灼热， 曝晒， 挤压， 冷冻伤， 钝性撕裂等; 化学因素常见的有 强酸、 强碱灼伤或石灰烫伤等。 机体在上述因素作用下可发生非 特异性炎症 5 表示为局部充血 水肿 分泌渗出增加 疼痛 9 甚 至出现皮肤损伤 坏死，但在局部不能查到特异的感染性病原体 故称为非特异性炎症。 非特异性炎症发生的机理在于， 正常情况 下机体生命活动的各个层次相互协调， 正常进行。 当物理的或化 学的变化因素急骤发生时 , 可直接破坏组织细胞的结构蚤白等成 分， 使细胞结构被破坏或引起细胞所处环境的恶化。 此时原有的 细胞代谢过程仍然延续， 从而导致局部环境中乳酸、 丙酮酸等三 羧酸循环的中间产物堆积， 并由于缺乏能量的供应和 H+的堆积， 使溶酶体膜的稳定性降低， 从而造成对自身细胞一系列的非特异 性炎症过程。 目前国内外对治疗非特异性炎症尚缺乏有效方法， 常采用局部沖洗、湿敷和输液的支持疗法，主要是对抗继发感染， 属于保守维持疗法， 不能控制和阻止进一步的扩大损伤， 因此需 要开发新的治疗药物。
本发明人在进行"生物波，，理论的研究过程中， 建立了生物波 动生长模型。 经过研究认识到， 这种波动有其内在的调节机制： 某些化学物质参与生物波动过程的调节， 把病态的周期性慢波转 变成正常的生理性混沌快波， 这类物质被称为促波因子。 经分离 提纯和鉴定， 确定一种促波因子为 N-乙酰氨基葡萄糖。 N-乙酰氨 基葡萄糖具有一般的手性药物的特点，又非同于一般的手性药物， 而表现出两种对映体的相互转变的自体振荡过程。 这种双相性改 变赋予 N-乙酰氨基葡萄糖以一种随机性的与体内成分如细胞、亚 细胞生物大分子等之间的高亲和力相互作用， 从而稳定这些成分 的构型、 构象， 阻止原有不良因素引起的改变继续扩大。
N-乙酰氨基葡萄糖是一种化学试剂， 二十世纪九十年代以来 陆续被用 于治疗牙周炎 ( W09102530A! )、 微生物感染 ( WO9718790A3 )、 炎性肠病 (
Figure imgf000003_0001
)、 角膜疾病 ( JP10287570A2 ), 前列腺肥大 (漏51篇15 ) 等疾病以及美容 ( JPS901370§A2 )¾ 洗发制剂 （JP2011505A2 )等。 目前尚无人将 其用于制备治疗物理 化学因素引起的非特异性炎症和控制症状 的药物制剂中。
本发明人惊异地发现， N-乙酰氨基葡萄糖及其药物可接受的 盐能迅速有效地治疗物理和 /或化学因素引起的非特异性炎症和 控制症状， 并且阻止损伤的进一步扩大， 从而完成了本发明。 发明内容
因此，本发明的一个目的是提供 N-乙酰氨基葡萄糖及其药物 学可接受的盐在治疗物理和 /或化学因素引起的非特异性炎症中 的应用。
本发明的另一个目的是提供 N-乙酰氨基葡萄糖及其药物学 可接受的盐在制备用于治疗物理和 /或化学因素引起的非特异性 炎症的药物中的应用。
本发明的再一个目的是提供治疗物理、 化学因素引起的非特 异性炎症的方法， 包括给病人包含有效量的 N-乙酰氨基葡萄糖或 其药物学可接受的盐的药物組合物。
本发明的上述目的是这样实现的： 采用 N-乙酰氨基葡萄糖或 其药物学可接受的盐作为活性成分， 任选地与本领域已知的各种 药物赋形剂或载体结合， 制备成水剂、 酒剂、 膏剂、 散剂或注射 剂型， 用于治疗和控制物理和 /或化学因素引起的非特异性炎症。
所述的 N-乙酰氨基葡萄糖全名为 N -乙酰基 - D -氨基葡萄 糖， 分子式为 C8H1SN06, 其结构式 （I )表示如下：
Figure imgf000004_0001
可用于本发明的 -乙酰基 - D -氨基葡萄糖的药物可接受 的盐的实例包括但不限于： 与无机酸形成的那些盐， 如盐酸盐、 氢溴酸盐、 硼酸盐、 磷酸盐、 硫酸盐、 硫酸氢盐和磷酸氢盐， 以 及与有机酸形成的那些盐， 如柠檬酸盐、 苯甲酸盐、 抗坏血酸盐、 甲基硫酸盐、 苦味酸盐、 富马酸盐、 马来酸盐、 丙二酸盐、 琥珀 酸盐、 酒石酸盐、 甲磺酸盐和葡萄糖小磷酸盐。
在本发明的药物组合物中， N-乙酰氨基葡萄糖或其药物可接 受的盐含量一般可为 0.1-10%重量。 如上所述， N-乙酰氨基葡萄糖或其药物学可接受的盐可以与 本领域已知的各种药物赋形剂或载体结合， 以制备成例如水剂、 酒剂、 膏剂、 散剂或注射剂型。 本发明的药物组合物可以通过各 种途径给药， 例如注射、 口服、 局部涂敷、 局部清洗， 或其组合。
根据药物组合物的剂型选择赋形剂或载体的种类和用量是本 领域的公知技术。 例如对于肠胃外给药， 可以将本发明药物的活 性成分 N-乙酰氨基葡萄糖或其药物学可接受的盐溶解或分散于 例如注射用水， 油性溶剂如脂油等， 制成溶液或悬浮液。 在肌内 或静脉应用时可用稀释剂如注射用 0.9%生理盐水、灭菌注射用水 或 0.5%盐酸利多卡因稀释， 还可再用 5%葡萄糖溶液或注射用 0.9%生理盐水进一步稀释。 或者， 为了制备外敷用的软膏剂， 可 以使用例如凡士林作为赋形剂 0
本发明的包含 N-乙酰氨基葡萄糖或其药物学可接受的盐的 药物组合物可以每天单剂量给药或多剂量给药 β 本发明药物组合 物的给药量根据给药对象的年龄、 病情、 需治疗的症状以及给药 方式等而变。但一般对于体重约为 75公斤成年病人来说，本发明 的药物組合物以每天 1-1000藝 亳克的剂量给药5 优选 10-1卿龍 亳克， 以活性組分计。
虽然不希望受特定理论的束缚， 但是据信， Ν-乙酰氨基葡萄 糖或其药物学可接受的盐通过调节生物波， 促进细胞再分布和稳 定不利环境下的溶酶体膜， 从而治疗并控制非特异性炎症和阻止 损伤的进一步扩大。 该化合物几乎没有毒性, 克服了激素等药物 应用于非特异性炎症治疗所带来的诸多副作用。 具体实施方式
下面结合实施例进一步说明本发明及其有益效果， 但是应该 明白， 这些实施例仅是为了举例说明本发明， 而不在任何方面构 成对本发明范围的限制。 实施例 1. 式 （I )化合物的促波试验
1、 试验材料和方法：
1.1 样品： 式 （I )化合物純品。
1.2 试猃材料：
菌种： 奇异变形杆菌应符合如下生化反应特征： 动力 (+)、 尿 素酶 (+)、 乳糖（ -）、 葡萄糖 (+)、 H2S( - )、 苯丙氨酸脱氨酶 (+)。
培养基： 改良 LB培养基（组成成分： 1 %胰蛋白胨、 0.5%酵 母提取物、 1 %氯化钠、 0.1%葡萄糖、 0.002%TTC、 PH7.2-7.4 )D
1.3 试验方法：
对照样： 在 LB平板中心点种奇异变形杆菌， 37 培养 9小 时；
试验样： 在 LIB平板中加入终浓度为 0 5%的式（Ϊ )化合物 5 同法点种奇异变形杆菌， 37 培养 9小时。
2、 试验结果及评价：
在对照样中显示出不断向外扩展 间隔 3小时的同 ^环； 在 试 样中3 不但形成每隔 3小时出现的同心环 而且与对照相比， 在每条环上显示出许多细小的波动环。
本试验采用生物波波动试验模型， 用以研究式（I )化合物的 促波作用， 结果可见式（I )化合物不仅可以使细菌细胞表现正常 的生物波特征， 而且使这种波动表现出更加微细的波动方式 , 表 明式（I )化合物对生物波动是有促进作用的。 这种促波作用有助 于解释式 （I ) 化合物治疗物理和 /或化学因素引起的非特异性炎 症及其症状控制的机理。 实施例 2. 式 （I )化合物的毒理试检 进行式 （I )化合物的毒理试验， 包括：
1、 急性毒理试验： 包括口服、 静脉注射和最大极限量给药试 验；
2、 Ames试验；
3、 小鼠骨髓细胞微核试验；
4、 鼠精子畸性试验；
5、 小鼠睾丸染色体畸变试验；
6、 慢性致死试验；
7、 亚慢性毒性 （90夭喂养）试验；
8、 传统致畸试验;
试臉结论表明： 式 （I )化合物急性毒性试验剂量超过 2g/kg 时， 仍未出现急性中毒反应； 在长期毒性试验中， 最高剂量已达 到 lg/kgs 经四周试验观察 未出现中毒反应； 在生殖试验中 5 从常规剂量 7醒 g/kg喂小鼠 5 经三次传代 s 证明式 （Ϊ )化合物对 小鼠受孕、 妊娠、 分娩、 哺乳及仔鼠发育均无影响。 这些试验证 明式（I )化合物属无毒物质。 实施例 3. 动物试臉
1、 烧伤试验:
选择 Wistar大鼠 20只， 随机分为 2組， 即对照組和试验组。 两组均采用纱布蒸馏水热捂的办法， 造成烧伤模型。 对照组动物 不进行治疗， 试验組动物采用"式 ( 1 )化合物 "固体粉末敷在局部 治疗。 结果 3天后， 试驗组大鼠有 8只结痂， 而对照组大鼠只有 2 只大鼠结痂， 且痂下仍有脓液积聚， 两者在烧伤反应上有明显 区别。
当用 N-乙酰氨基葡萄糖盐酸盐代替 N-乙酰氨基葡萄糖进行 试验时， 试验組大鼠有 6只结痂， 创面修复完好， 与对照组有显 著差别。
1、 钝性撕裂动物试验
随机选取昆明种小鼠 30只， 随机分为 2组， 即对照組 10只 和试验组 20只。 两组均采用钝性撕裂的方法，对小鼠后肢的大腿 肌肉造成飩性撕裂后組织的非特异性损伤。 表现为受伤侧肢体不 能自由伸屈和随意运动， 局部肿胀， 疼痛 （不能触摸）。 对照組 10只小鼠正常饲养，试验组给 N-乙酰氨基葡萄糖水溶液， 药物浓 度为 5%重量， 10只以腹腔注射， 10只以局部肌肉注射方式给药， 注射量均为 1亳升。 结果用药 7天后， 两组之间动物反应不同。 对照组动物病变在原有基础上继续发展或维持， 有 4只发展为受 伤侧肢瘫痪， 并且另有 4只伸屈功能障碍。 试验组小鼠除 1只瘫 痪外（出现于腹腔注射组）， 其佘均可自由地活动。 两组相比， 差 别非常显箸 β
该试验中当用 Ν-乙酰氨基葡萄糖硫酸盐代替 Ν-乙酰氨基葡 萄糖时 （剂量、 给药方法等均同上）， 得到同上所述相近的结杲。 试验组有 2只小鼠出现伸屈功能障碍, 2只受伤侧肢瘫痪， 与对 照组相比 有较明显差别 Β 实施例 4. 烧伤治疗试验
在第三军医大学西南医院烧伤科联合研究中，曾选择 10例烧 伤病人， 在其自愿情况下对创面使用 Ν-乙酰氨基葡萄糖无菌散 剂， 使用剂量根据创面大小不等， 连续使用 3天， 从第 4天起观 察，可见创面四周的新生组织不断生出，每天向中心扩张 l-2mm， 同时伴随水肿减轻， 血管慢慢收缩， 分泌物减少。 实施例 5. 外伤治疗试验
收集 8例外伤患者， 多为面部和前臂擦伤。 以 N-乙酰氨基葡 萄糖少许与凡士林加在一起制成涂膏，浓度为 1克 /10克，涂在患 部， 使用剂量根据创面大小不等， 连用 3天。 可见面部擦伤创面 迅速愈合并且面部不留疤痕。 实施例 6. 冷冻伤治疗试验
在学员中观察 20名具有不同程度冷冻伤的患者，试验组采用 N-乙酰氨基葡萄糖 10%重量水溶液局部给药，根据症状和个体情 况，给药剂量分别为每日 1亳升至 10亳升不等。试验組表现为早 期恢复， 进而消炎消肿。 另 10名对照组， 症状一直持续， 红、 肿、 痛的炎性表现明显。

Claims

权 利 要 求
1. N-乙酰氨基葡萄糖或其药物可接受的盐在制备用于治疗物 理、 化学因素引起的非特异性炎症的药物中的应用。
2. 权利要求 1 的应用， 其中所述药物为水剂、 酒剂、 膏剂、 散剂或注射剂型。
3. 权利要求 1或 2的应用， 其中所述药物中 N-乙酰氨基葡萄 糖的浓度为 0.1-10%重量。
4. 权利要求 1或 2的应用，其中所述药物以 l-100000mg/天〃 5 公斤体重的剂量给药， 剂量以活性组分计。
5. 治疗物理、 化学因素引起的非特异性炎症的方法， 包括给 病人包含有效量的 N-乙酰氨基葡萄糖或其药物学可接受的盐的 药物组合物 β
6. 权利要求 5的方法 s 其中所迷药物组合物为水剂 酒剂 膏剂、 散剂或注射剂型。
7. 权利要求 5或 6的方法，其中所述药物以 l-100000mg/天 /75 公斤体重的剂量给药 剂量以活性组分计 a
8. N-乙酰氨基葡萄糖或其药物可接受的盐在治疗物理、 化学 因素引起的非特异性炎症中的应用。
PCT/CN2004/000280 2003-03-27 2004-03-29 Utilisation de n-acetyl-d-aminoglycosamine dans le traitement d'inflammations non specifiques associees a des facteurs physiques ou chimiques WO2004084915A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US10/551,258 US20070178161A1 (en) 2003-03-27 2004-03-29 Use of n-acetryl-d-glucosamine in treating and controlling non-specific inflammations caused by physical or chemical factors
JP2006504206A JP2006521298A (ja) 2003-03-27 2004-03-29 物理的又は化学的因子により生じる非特異的炎症の治療及び抑制におけるｎ‐アセチル‐ｄ‐グルコサミンの使用
EP04723952A EP1611894A4 (en) 2003-03-27 2004-03-29 USE OF N-ACETYL-D-AMINOGLYCOSAMINE IN THE TREATMENT OF NON-SPECIFIC INFLAMMATIONS ASSOCIATED WITH PHYSICAL OR CHEMICAL FACTORS

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN03108278.5 2003-03-27
CNB031082785A CN1232257C (zh) 2003-03-27 2003-03-27 N－乙酰氨基葡萄糖在制备治疗和控制物理化学因素致非特异性炎症的药物中的应用

Publications (1)

Publication Number Publication Date
WO2004084915A1 true WO2004084915A1 (fr) 2004-10-07

Family

ID=33035134

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2004/000280 WO2004084915A1 (fr) 2003-03-27 2004-03-29 Utilisation de n-acetyl-d-aminoglycosamine dans le traitement d'inflammations non specifiques associees a des facteurs physiques ou chimiques

Country Status (5)

Country Link
US (1) US20070178161A1 (zh)
EP (1) EP1611894A4 (zh)
JP (1) JP2006521298A (zh)
CN (1) CN1232257C (zh)
WO (1) WO2004084915A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2005112948A1 (ja) * 2004-05-21 2008-03-27 国立大学法人鳥取大学 創傷の治療又は処置のための薬剤

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021029443A1 (en) * 2019-08-14 2021-02-18 RIM, Chol Hak Local hemostatic composition

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5913708A (ja) 1982-07-14 1984-01-24 Shiseido Co Ltd 化粧料
US4772591A (en) 1985-09-25 1988-09-20 Peritain, Ltd. Method for accelerated wound healing
EP0372730A2 (en) * 1988-11-18 1990-06-13 University Of British Columbia N-acetyl glucosamine as a cytoprotective agent
WO1990008549A1 (de) 1989-01-26 1990-08-09 Ulrich Speck N-acetylglucosamin-zubereitungen zur buccalen anwendung
US5217962A (en) * 1992-01-28 1993-06-08 Burton Albert F Method and composition for treating psoriasis
US5623064A (en) 1993-12-01 1997-04-22 Marine Polymer Technologies, Inc. Poly-β-1→-4-N-acetylglucosamine
WO1997018790A2 (en) 1995-11-22 1997-05-29 The Research And Development Institute, Inc. Therapeutic and diagnostic agents for the treatment of microbial infections
JPH10287570A (ja) 1997-04-09 1998-10-27 Seikagaku Kogyo Co Ltd 角膜障害症治癒促進剤
US6046179A (en) 1998-04-17 2000-04-04 Murch; Simon Composition for and treatment of inflammatory bowel disease by colon administration of N-acetylglucosamine
CN1372931A (zh) 2001-02-28 2002-10-09 中国人民解放军第三军医大学 N－乙酰－d－氨基葡萄糖在制备治疗宫颈糜烂药物中的应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3232836A (en) * 1959-08-24 1966-02-01 Pfizer & Co C Facilitating healing of body surface wounds by intravenous administration of n-acetyl glucosamine, glucosamine, or pharmaceutically acceptable acid salts of glucosamine
US4647453A (en) * 1984-10-18 1987-03-03 Peritain, Ltd. Treatment for tissue degenerative inflammatory disease

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5913708A (ja) 1982-07-14 1984-01-24 Shiseido Co Ltd 化粧料
US4772591A (en) 1985-09-25 1988-09-20 Peritain, Ltd. Method for accelerated wound healing
EP0372730A2 (en) * 1988-11-18 1990-06-13 University Of British Columbia N-acetyl glucosamine as a cytoprotective agent
WO1990008549A1 (de) 1989-01-26 1990-08-09 Ulrich Speck N-acetylglucosamin-zubereitungen zur buccalen anwendung
US5217962A (en) * 1992-01-28 1993-06-08 Burton Albert F Method and composition for treating psoriasis
US5623064A (en) 1993-12-01 1997-04-22 Marine Polymer Technologies, Inc. Poly-β-1→-4-N-acetylglucosamine
WO1997018790A2 (en) 1995-11-22 1997-05-29 The Research And Development Institute, Inc. Therapeutic and diagnostic agents for the treatment of microbial infections
JPH10287570A (ja) 1997-04-09 1998-10-27 Seikagaku Kogyo Co Ltd 角膜障害症治癒促進剤
US6046179A (en) 1998-04-17 2000-04-04 Murch; Simon Composition for and treatment of inflammatory bowel disease by colon administration of N-acetylglucosamine
CN1372931A (zh) 2001-02-28 2002-10-09 中国人民解放军第三军医大学 N－乙酰－d－氨基葡萄糖在制备治疗宫颈糜烂药物中的应用

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2005112948A1 (ja) * 2004-05-21 2008-03-27 国立大学法人鳥取大学 創傷の治療又は処置のための薬剤

Also Published As

Publication number Publication date
JP2006521298A (ja) 2006-09-21
CN1232257C (zh) 2005-12-21
CN1533774A (zh) 2004-10-06
US20070178161A1 (en) 2007-08-02
EP1611894A4 (en) 2007-10-10
EP1611894A1 (en) 2006-01-04

Similar Documents

Publication Publication Date Title
US20090191288A1 (en) Composition to Treat Herpes, Pseudomonas, Staph, Hepatitis and Other Infectious Diseases
BG64522B1 (bg) Средство за лечение на вирусни инфекциозни заболявания
US9662360B2 (en) Treatment of herpes, pseudomonas, staph, and hepatitis
NO832392L (no) Fenyl-alfa-acyloksyacetamid-derivater og deres terapeutiske benyttelse, samt fremstilling derav
CN101518522A (zh) 大蒜素外用制剂及其制备方法
EP0988040A1 (en) Use of glucosamine and glucosamine derivatives for quick alleviation of itching or localized pain
US6992073B2 (en) Use of N-acetyl-D-glucosamine in the manufacture of a medicament for treating cervical erosion
WO2004084915A1 (fr) Utilisation de n-acetyl-d-aminoglycosamine dans le traitement d'inflammations non specifiques associees a des facteurs physiques ou chimiques
CN100408041C (zh) 一种治疗外阴和/或阴道感染疾病的药物组合物
US7704976B2 (en) Use of N-acetyl-D-glucosamine for preparing medicines for urogenital tract infection's treatment and prevention
US4753942A (en) Method for the treatment of inflammatory conditions
WO2018161890A1 (zh) 小檗碱在制备治疗急性软组织损伤的药物中的应用
US8765717B2 (en) Meloxicam and glucosamine formulation and uses thereof
KR20040018335A (ko) 성 기능 장애의 예방 및 치료에 유용한 약제의 제조에서ｎ-아세틸-ｄ-글루코사민의 용도
WO2002067946A1 (fr) Utilisation de la n-acetyl-d-glucosamine dans la preparation de compositions pharmaceutiques utilisees dans la suppression des effets secondaires causes par la radiotherapie et la chimiotherapie
CN112156088B (zh) 一种化合物在制备结核分枝杆菌抑制剂中的用途
WO2002067947A1 (fr) Utilisation de n-acetyl-d-glucosamine dans la preparation de compositions pharmaceutiques utilisees dans le traitement adjuvant d'une maladie anoperineale
US20070197470A1 (en) Use of n-acetyl-d-aminogylcosamine in preparation of drugs for modulating microorganisms on mucous membrane
WO2002067944A1 (fr) Utilisation de n-acetyl-d-glucosamine dans la fabrication d'un produit pharmaceutique destine au traitement du mal des transports
JP2001163782A (ja) 皮膚疾患治療用外用剤
WO2004084913A1 (fr) Utilisation de n-acetyl-d-aminoglycosamine pour le traitement de lesions locales ou de symptomes systematiques associes a des reactions auto-immunes
JPH0725686B2 (ja) 胃潰瘍治療薬
KR20040012779A (ko) 외음부질염 및 질증을 치료하기 위한 항진균제를 포함하는조성물
JPS58500326A (ja) 炎症性ビ−ルス感染症、にきび、皮膚炎及び関節炎の治療
JP2001163781A (ja) 皮膚組織障害治療・予防・改善用外用剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DPEN Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2006504206

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 2004723952

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2004723952

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2007178161

Country of ref document: US

Ref document number: 10551258

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 10551258

Country of ref document: US