枯草芽孢杆菌 | 68038-70-0

• 物质功能分类: 原料药 - 抗生素类药物 - 多肽类药
• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 中文名称: 枯草芽孢杆菌
• 中文别名: 杆菌肽锌；妥尔油脂肪酸
• 英文名称: Caswell No. 909A
• 英文别名: 4-[[2-[[2-(1-amino-2-methylbutyl)-4,5-dihydro-1,3-thiazole-4-carbonyl]amino]-4-methylpentanoyl]amino]-5-[[1-[[3-(2-amino-2-oxoethyl)-18-(3-aminopropyl)-12-benzyl-15-butan-2-yl-6-(carboxymethyl)-9-(4H-imidazol-4-ylmethyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclopentacos-21-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid;zinc
• CAS: 68038-70-0；1405-89-6
• 化学式: C66H103N17O16SZn
• 分子量: 1488.1
• InChiKey: QSNOBVJFKSQBBD-UHFFFAOYSA-N

物化性质

• 熔点：
  250 °C (dec.)
• 溶解度：
  10 mM HCl：5 mg/mL，澄清，微黄绿色
• LogP：
  -1.852 (est)
• 颜色/状态：
  Dry off-white to tan solid
• 密度：
  26-29 lb/cu ft

计算性质

• 辛醇/水分配系数(LogP)：
  -1.77
• 重原子数：
  101
• 可旋转键数：
  31
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  552
• 氢给体数：
  16
• 氢受体数：
  21

ADMET

毒理性

• 毒性总结

鉴定和使用：枯草杆菌是一种杆状、革兰氏阳性、需氧、能动的（周生鞭毛）细菌，在自然界中广泛存在。枯草杆菌常见于各种生态位，包括土壤、水和空气。该细菌通常产生蛋白酶和其他酶，这就是为什么该细菌的菌株常用于工业生产酶和其他化学品。该细菌还能产生一种内生孢子，使生物体能够耐受极端环境条件。它被用作微生物杀虫剂。人体研究：芽孢杆菌是一个大而多样的细菌属，包括苏云金芽孢杆菌、地衣芽孢杆菌、短小芽孢杆菌、蜡样芽孢杆菌和炭疽芽孢杆菌等物种。其中两种，B. cereus和B. anthracis，已知对人类和动物有病原性。因此，能够区分物种是非常重要的。存在生物化学测试和其他工具，可以正确识别所讨论的生物体，即B. subtilis。枯草杆菌种已知产生枯草菌素酶，据报道，在工业环境中反复接触该酶的个体会产生过敏或超敏反应。动物研究：一系列测试确定QST 713技术产品不具有病原性且无显著毒性。急性口服毒性/病原性、急性肺毒性/病原性和急性静脉毒性/病原性研究显示无显著毒性和缺乏病原性。正如任何微生物杀虫剂所预期的那样，QST 713确实引起了一种非常轻微的迟发型超敏反应，被认为是一种潜在的皮肤致敏剂。

IDENTIFICATION AND USE: Bacillus subtilis is a rod-shaped, gram positive, aerobic, motile (peritrichous flagella) bacterium that is ubiquitous in nature. Bacillus subtilis is commonly found in various ecological niches including soil, water and air. The bacterium commonly produces proteases and other enzymes which is why strains of the bacterium are commonly used for industrial production of enzymes and other chemicals. The bacterium also can produce an endospore which allows the organism to endure extreme environmental conditions. It is used as a microbial pesticide. HUMAN STUDIES: The genus Bacillus is a large, diverse genus of bacteria that includes species such as thuringiensis, licheniformis, pumilis, cereus and anthracis. Two of these species, B. cereus and B. anthracis, are known to be pathogenic to humans and animals. Because of this, the ability to differentiate species is extremely important. Biochemical tests and other tools exist which allow for the proper identification of the organism in question, B. subtilis. The Bacillus subtilis species is known to produce the enzyme subtilisin which has been reported to produce allergenic or hypersensitivity reactions to individuals repeatedly exposed to the enzyme in industrial settings. ANIMAL STUDIES: A battery of tests determined that QST 713 Technical product is not pathogenic and has no significant toxicity. The acute oral toxicity/pathogenicity, acute pulmonary toxicity/pathogenicity, and acute intravenous toxicity/ pathogenicity studies demonstrated no significant toxicity and a lack of pathogenicity. As would be expected for any microbial pesticide, QST 713 did elicit a very mild delayed hypersensitivity response and is considered a potential dermal sensitizer.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

枯草杆菌在其肉汤培养物的上清液中含有的代谢物特征被描述。这些代谢物含有细菌产生的生物活性成分，确保细胞生长和繁殖。这些成分对人类和动物胃肠道中的革兰氏阳性菌和革兰氏阴性菌病原体和条件性病原体具有抑菌和杀菌作用。细菌产生的酶（淀粉酶、蛋白酶、纤维素分解酶、脂肪酶、果胶酶）增加了制剂的拮抗性质，并促进其益生菌效果。

Characteristics of Bacillus subtilis metabolites contained in supernatants of its broth cultures are described. Metabolites contained bacterium-produced biologically active components ensuring cells growth and propagation. These components had bacteriostatic and bactericidal effect on gram-positive and gram-negative pathogenic and conditionally pathogenic microflora of gastrointestinal tract of human and animals. Enzymes produced by the bacterium (amylase, protease, cellulose-decomposing enzyme, lipase, pectinase) increased antagonistic properties of preparation and promote its probiotic effect.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

黄曲霉毒素B1（AFB1）因其广泛存在以及对公众健康的严重威胁，包括其致畸、致癌和致突变效应而受到关注。本研究旨在评估AFB1的毒性，并评估枯草杆菌ANSB060对黄河鲤鱼黄曲霉毒素中毒的改善效果。共750尾黄河鲤鱼幼鱼被分配到五个饮食处理组，持续60天。饮食C0代表负对照组，含有约50微克AFB1/千克饮食的M0饮食代表正对照组，而M0.25、M0.5和M1.0饮食则是在M0饮食中分别补充了0.25x10^9、0.5x10^9和1.0x10^9 CFU/千克饮食的枯草杆菌ANSB060。结果显示，补充菌株ANSB060可以恢复AFB1诱导的鲤鱼体重下降，并提高饲料转化率。ANSB060还可以缓解肝脏形态的变化，改善肝胰腺和肠道的消化酶活性，以及减少鲤鱼肝胰腺和性腺中AFB1的残留。结论是，ANSB060对患有黄曲霉毒素中毒的鲤鱼具有保护作用，并在饲料工业应用中具有潜在的应用前景。

Aflatoxin B1 (AFB1) elicits serious threats to public health due to its widespread occurrence, as well as its teratogenic, carcinogenic and mutagenic effects. This study aimed to evaluate the toxicity of AFB1 and assess the ameliorative efficacy of Bacillus subtilis ANSB060 on aflatoxicosis in Yellow River carp. A total of 750 juvenile Yellow River carp were allocated into five dietary treatments for 60 days. Diet C0 represented for the negative control, diet M0 containing about 50 ug AFB1/kg diet represented for the positive control, and diet M0.25, M0.5 and M1.0 was diet M0 supplemented with B. subtilis ANSB060 at a dose of 0.25x109, 0.5x109 and 1.0x109 CFU/kg diet, respectively. The results showed that supplementation of strain ANSB060 restored the reduced body weight and enhanced feed conversion ratio of carp induced by AFB1 towards normal. ANSB060 could also relieve the alterations in hepatic morphology, improve digestive enzyme activities of hepatopancreas and intestine, as well as decrease AFB1 residues in carp's hepatopancreas and gonad. It is concluded that ANSB060 has a protective effect in carp with aflatoxicosis, with a promising potential in feed industrial applications.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

无机三价砷是一种主要的环境污染物，人类暴露于其中会导致许多病理变化，包括角化病和癌症。在这里，我们分析了在砷酸钠氧化应激条件下，B. subtilis芽孢对人类正常角质细胞的影响。在诱导氧化应激之前，用芽孢预处理细胞能够保持正常的细胞内ROS、GSH和脂质过氧化水平，以及抑制MAPK级联的激活。此外，芽孢对细胞增殖显示出积极效果，这可能是由于它们与细胞表面的结合以及内源性过氧化氢酶的激活。我们发现芽孢通过Nrf-2的核转位发挥其保护作用，Nrf-2参与激活应激反应基因。这反过来又对砷酸钠应激损伤产生了保护作用，因为当细胞在用芽孢预处理之前受到应激时，氧化应激标志物被恢复到生理水平。因此，B. subtilis芽孢可以被认为是一种新的对抗正常人类角质细胞氧化应激的制剂。

Inorganic trivalent arsenic is a major environmental pollutant and exposure to human results in many pathologies, including keratosis and carcinoma. Here, we analyzed the effects of B. subtilis spores on human normal keratinocytes in the presence of sodium arsenite oxidative stress. Pre-treatment of cells with spores before inducing oxidative stress was able to keep normal levels of intracellular ROS, GSH and lipid peroxidation, as well as to inhibit the activation of the MAPK cascade. Moreover, spores showed a positive effect on cell proliferation, probably due to their binding on the cell surface and the activation of intracellular catalases. We found that spores exert their protective effect by the nuclear translocation of Nrf-2, involved in the activation of stress response genes. This, in turn, resulted in a protective effect against sodium arsenite stress injury, as oxidative stress markers were reported to physiological levels when cells were stressed before incubating them with spores. Therefore, B. subtilis spores can be considered as a new agent to counteract oxidative stress on normal human keratinocytes.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

立即急救：确保已经进行了充分去污。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、气囊面罩装置或口袋面罩，按训练进行操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者向前倾或将其置于左侧（如果可能，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。/病原体/

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Etiological Agents/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

饲料添加剂：杆菌肽锌与杆菌肽 杆菌肽锌

杆菌肽锌是杆菌肽与锌离子形成的络合物，属于多肽类抗生素。目前它是最广泛应用的抗生素类饲料添加剂之一，含锌量一般在2%～12%之间。

特性：

• 人工合成产品为白色或微黄色粉末状，具有特臭气味。
• 易潮解并形成弱碱性物质，易溶于水、甲醇及乙醇中。
• 对革兰氏阳性菌有强烈抗菌效果，并对部分革兰氏阴性菌也有一定作用。

在猪全价饲料中的添加浓度一般为10～100mg/kg。杆菌肽锌不被肠道吸收，在猪体内无残留问题，是一种安全可靠的抗生素类药物添加剂。然而，该产品毒性较强且不易被肠吸收，因此不适合用于全身性感染的治疗。

杆菌肽

杆菌肽是从苔藓样杆菌（Bacillus licheniformis）培养液中提取的一种多肽类抗生素。呈白色或淡黄色粉末状，无臭或微臭，味苦并具有吸湿性。易溶于水及乙醇，但在室温下不稳定，在pH值小于3时容易析出，并在pH值大于9时变得不稳。溶解后需存放在冰箱内冷藏，每毫克的效价不得少于55杆菌肽单位。

抗菌作用：

• 对革兰氏阳性菌具有较强的抗菌作用。
• 对革兰氏阴性菌无效。
• 适用于耐药性金黄色葡萄球菌（Staphylococcus aureus）严重感染。
• 内服不被吸收，仅用于肠道感染。
• 外用对敏感菌引起的体表、口腔、眼部感染及乳房炎有效。
• 长期使用可能损害肾脏。

杆菌肽锌是一种比杆菌肽更稳定的盐类药物。它在饲料中作为添加剂使用时，具有促进畜禽生长发育、预防肠道感染和提高饲料报酬等作用，其添加浓度与杆菌肽相同。

作用与用途 杆菌肽锌

• 对革兰氏阳性菌有较强的抗菌作用。
• 剂量一般为10～100mg/kg。大部分药物在2天内随粪便排出，不易残留于畜禽产品中。
• 细菌对杆菌肽锌产生耐药性的速度较慢，与其他抗生素之间无交叉耐药性。
• 与青霉素、链霉素、新霉素及多黏菌素等具有协同作用。

杆菌肽

• 属窄谱抗生素，主要针对革兰氏阳性菌有强大抗菌作用，对螺旋体和放线菌也有一定效果。
• 对革兰阴性杆菌无效。
• 可内服治疗家畜细菌性腹泻及猪的密螺旋体性痢疾。
• 与其他抗生素如青霉素、链霉素等联合使用可增强疗效。

总结

杆菌肽锌与杆菌肽均属于多肽类抗生素，对特定类型细菌具有显著的抗菌作用。它们主要用于促进畜禽生长、防治畜禽细菌性腹泻及由密螺旋体引起的猪血痢。尽管这些药物在饲料中作为添加剂时较为安全可靠，但使用时仍需严格遵循相关指南和规定。

文献信息

• Gastrin releasing peptide compounds
  申请人：——

  公开号：US20040253225A1

  公开（公告）日：2004-12-16

  New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is an optical label or a metal chelator (in the form complexed with a metal radionuclide or not), N—O—P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.

  本发明提供了用于诊断成像或治疗的新型化合物，其化学式为M-N—O—P-G，其中M是光学标记物或金属螯合剂（形式上与金属放射性核素络合或未络合），N—O—P是连接剂，G是GRP受体靶向肽。本发明还提供了使用该化合物对患者进行成像和/或提供放射治疗或光治疗的方法。还提供了制备诊断成像剂的方法和试剂盒。还提供了制备放射治疗剂的方法和试剂盒。
• Gastrin Releasing Peptide Compounds
  申请人：Cappelletti Enrico

  公开号：US20080008649A1

  公开（公告）日：2008-01-10

  New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure: wherein R 1 -R 5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided. Novel methods of treating prostate tumors or of delaying the progression of prostate tumors are also provided, including, methods of treating bone or soft tissue metastases of prostate cancer, methods for treating hormone sensitive and hormone refractory prostate cancer, methods for delaying the progression of hormone sensitive prostate cancer, for facilitating combination therapy in patients with hormone sensitive prostate cancer and for decreasing aberrant vascular permeability in patients with hormone sensitive prostate cancer.

  新的和改进的化合物可用于诊断成像或治疗，其化学式为M-N—O—P-G，其中M是具有以下结构的金属螯合剂： 其中R1-R5和FG如此定义（以金属放射性核素或未配合的形式），N—O—P是含有至少一个非α氨基酸环状基团、至少一个取代胆酸或至少一个非α氨基酸的连接物，而G是GRP受体靶向肽。在首选实施例中，M是Aazta金属螯合剂或其衍生物。本发明还提供了使用该化合物对患者进行成像和/或提供放射治疗或光治疗的方法。还提供了制备诊断成像试剂的方法和试剂盒。还提供了制备放射治疗试剂的方法和试剂盒。还提供了治疗前列腺肿瘤或延缓前列腺肿瘤进展的新方法，包括治疗前列腺癌骨骼或软组织转移的方法，治疗激素敏感和激素难治性前列腺癌的方法，延缓激素敏感前列腺癌进展的方法，促进激素敏感前列腺癌患者联合治疗的方法以及降低激素敏感前列腺癌患者异常血管渗透性的方法。
• GASTRIN RELEASING PEPTIDE COMPOUNDS
  申请人：Cappelletti Enrico

  公开号：US20110052491A1

  公开（公告）日：2011-03-03

  New and improved compounds for use in diagnostic imaging or therapy having the formula M—N—O—P—G, wherein M is an optical label or a metal chelator (in the form complexed with a metal radionuclide or not), N—O—P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.

  本发明涉及用于诊断成像或治疗的新型化合物，其化学式为M—N—O—P—G，其中M是光学标记或金属螯合剂（以与金属放射性核素形成络合物或非络合形式存在），N—O—P是连接剂，G是GRP受体靶向肽。本发明还提供了使用该化合物进行患者成像和/或提供放射治疗或光疗的方法。本发明还提供了制备诊断成像剂的方法和试剂盒。本发明还提供了制备放射治疗剂的方法和试剂盒。
• New therapeutic approaches for treating neuroinflammatory conditions
  申请人：Pharnext

  公开号：EP2236158A1

  公开（公告）日：2010-10-06

  The present invention discloses new compositions which can be used for the treatment of the neuroinflamation, in particular associated with neurodegenerative, autoimmune, infectious, toxic or traumatic disorders. More particularly, the invention relates to combined therapies for treating neuroinflammation by affecting extravasation cascade. The invention also discloses new methods for treating neuroinflammation pathological conditions in a subject.

  本发明公开了可用于治疗神经炎症的新组合物，尤其是与神经退行性疾病、自身免疫性疾病、感染性疾病、毒性疾病或创伤性疾病有关的神经炎症。更具体地说，本发明涉及通过影响外渗级联来治疗神经炎症的综合疗法。本发明还公开了治疗受试者神经炎症病理条件的新方法。
• IMPROVED GASTRIN RELEASING PEPTIDE COMPOUNDS
  申请人：Bracco Imaging, S.P.A.

  公开号：EP1706154A1

  公开（公告）日：2006-10-04