LY83583inhibitor of soluble guanylate cyclase and of cGMP production |
Sample solution is provided at 25 µL, 10mM.
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- Purity = 98.00%
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Cas No. | 91300-60-6 | SDF | Download SDF |
Chemical Name | 6-(phenylamino)-5,8-quinolinedione | ||
Canonical SMILES | O=C1C=C(Nc2ccccc2)C(=O)c2cccnc12 | ||
Formula | C15H10N2O2 | M.Wt | 250.3 |
Solubility | ≤3.8mg/ml in ethanol;25mg/ml in DMSO;25mg/ml in dimethyl formamide | Storage | Store at -20°C |
Physical Appearance | A crystalline solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. |
LY83583 is an inhibitor of soluble guanylate cyclase and of cGMP production [1].
Soluble Guanylate cyclase (sGC) is a heterodimeric enzyme involved in converting guanosine triphosphate to cyclic guanosine monophosphate. Soluble Guanylate cyclase is a critical component of the NO/cGMP signaling pathway, which has been involved in a number of important physiological processes, including smooth muscle relaxation and neurotransmission [2].
In human platelets, LY 83583 significantly antagonized the inhibitory effect of sodium nitroprusside and EDRF. LY 83583 attenuated the increases in intracellular cyclic GMP by sodium nitroprusside and EDRF [1]. Low concentrations of LY 83583 (≤ 0.1 μM) inhibited endothelium-dependent relaxations of rabbit aortic strips induced by acetylcholine or by the calcium ionophore A23187. Higher concentrations (≥ 0.3 μM) produced partial inhibition of relaxation to sodium nitroprusside and glyceryl trinitrate. LY 83583 (10 μM) showed no effect on cyclic AMP-mediated relaxations induced by isoprenaline or forskolin [3]. In cultured endothelial cells, treatment with LY 83583 (1 μM) rapidly and reversibly inhibited EDRF release. In the rat gastric fundus, LY 83583 (10 μM) inhibited the relaxation induced by nitric oxide (NO) [4]. In activated human neutrophils, LY-83583 (100 μM) inhibited the release of both LF and MPO after stimulation with FMLP or A-23187. LY-83583 reduced the cGMP-dependent protein kinase (G-kinase) activity [5].
References:[1] Mülsch A, Lückhoff A, Pohl U, et al. LY 83583 (6-anilino-5, 8-quinolinedione) blocks nitrovasodilator-induced cyclic GMP increases and inhibition of platelet activation[J]. Naunyn-Schmiedeberg"s archives of pharmacology, 1989, 340(1): 119-125.[2] Denninger J W, Marletta M A. Guanylate cyclase and the NO/cGMP signaling pathway[J]. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1999, 1411(2): 334-350.[3] Mülsch A, Busse R, Liebau S, et al. LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase[J]. Journal of Pharmacology and Experimental Therapeutics, 1988, 247(1): 283-288.[4] Barbier A J M, Lefebvre R A. Effect of LY 83583 on relaxation induced by non-adrenergic non-cholinergic nerve stimulation and exogenous nitric oxide in the rat gastric fundus[J]. European journal of pharmacology, 1992, 219(2): 331-334.[5] Wyatt T A, Lincoln T M, Pryzwansky K B. Regulation of human neutrophil degranulation by LY-83583 and L-arginine: role of cGMP-dependent protein kinase[J]. American Journal of Physiology-Cell Physiology, 1993, 265(1): C201-C211.
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1、该制剂为肌肉注射;
2、制备该微球过程中用到了二氯甲烷、乙醇、正庚烷、二甲基硅油。国家药典有机溶剂残留规定:二氯甲烷残留限度为0.06%;乙醇残留限度为0.5%;正庚烷残留限度0.5%;二甲基硅油药典中还为収载。目前自制微球的二氯甲烷残留约0.2%左右,正庚烷残留1.0%左右,乙醇残留0.3%左右,二甲基硅油暂未检测。很明显:二氯甲烷和正庚烷超标。后来测了一下原研制剂的有机溶剂残留:二氯甲烷残留约0.1%左右,正庚烷残留1.5%左右,乙醇残留0.2%左右。本人也制剂新手,请各位大神帮帮忙,积极发言。我这个长效缓释PLGA微球制剂中有机溶剂残留限应该定多少合适,我后期优化工艺时对上述有机残留应该控制到多少一下合适。
我最近用乳化交联法制备壳聚糖盐酸盐微球,药物是水不溶性(醋酸共晶体),将药物乙醇溶液加入到3%壳聚糖盐酸盐溶液中,混合均匀,加入到含2%span80的液体石蜡,油水比6:1,乳化半小时,加入1.5ml戊二醛,交联30min,离心,用石油醚,丙酮各洗两次,干燥,得微球。
但是我研磨微球,用乙醇溶解药物,超声3h,在紫外下根本检测不到药物,包封率就没法算,我测了药物在石油醚和丙酮中都有一定的溶解度,洗的时候溶剂层也有药物的颜色,是不是微球中的药物都被洗了出来?还是只是把游离的药物洗了出来?药物根本就没被包进去?但是药物在有机溶剂中都有一定的溶解度,我该怎么做?有大神愿意告知一二吗????
版主shitou0307留言:
因为你还没学会怎么提问
我理解就是一个是包裹,一个是镶嵌
1.微囊的形态与粒径及分布
2.微囊的载药量与包封率
3.微囊药物的释放速率
4.有机溶剂残留量
微囊与微球的载体材料
常用的载体材料:
1.天然高分子材料
(1)明胶
明胶是由氨基酸与肽交联形成的直链聚合物。
明胶分酸法明胶(A型)和碱法明胶(B型)。A型明胶等电点为7~9,B型明胶稳定而不易长菌,等电点为4.7~5.0。两者的成囊性无明显差别,作囊材的用量为20~100g/L 。
可生物降解,几乎无抗原性。
(2) 阿拉伯胶
一般常与明胶等量配合使用,作囊材的用量为20~100g/L,亦可与白蛋白配合作复合材料。
(3) 海藻酸盐
系多糖类化合物,常用稀碱从褐藻中提取而得。海藻酸钠可溶于不同温度的水中,不溶于乙醇、乙醚及其它有机溶剂;不同Mav产品的粘度有差异。可与甲壳素或聚赖氨酸合用作复合材料。因海藻酸钙不溶于水,故海藻酸钠可用CaCl2固化成囊。
(4) 壳聚糖
壳聚糖是由甲壳素脱乙酰化后制得的一种天然聚阳离子型多糖,可溶于酸或酸性水溶液,无毒、无抗原性,在体内能被溶菌酶等酶解,具有优良的生物降解性和成膜性,在体内可溶胀成水凝胶。
2.半合成高分子材料
作囊材的半合成高分子材料多系纤维素衍生物,其特点是毒性小、粘度大、成盐后溶解度增大。
(1) 羧甲基纤维素盐(CMC-Na)
常与明胶配合作复合囊材,一般分别配1~5g/L CMC-Na及30g/L明胶,再按体积比2:1混合。CMC-Na遇水溶胀,体积可增大10倍,在酸性液中不溶。水溶液粘度大,有抗盐能力和一定的热稳定性,不会发酵,也可以制成铝盐CMC-A1单独作囊材。
(2)醋酸纤维素酞酸酯(CAP)
在强酸中不溶解,可溶于pH>6的水溶液,在二氧六环、丙酮中溶解,水、乙醇中不溶。用作囊材时可单独使用,用量一般在30g/L左右,也可与明胶配合使用。
(3)乙基纤维素(EC)
化学稳定性高,适用于多种药物的微囊化,不溶于水、甘油或丙二醇,可溶于乙醇,易溶于乙醚,遇强酸易水解,故对强酸性药物不适宜。用乙基纤维素为囊材时,可加入增塑剂改善其可塑性。
(4)甲基纤维素(MC)
在水中溶胀成澄清或微浑浊的胶体溶液,在无水乙醇、氯仿或乙醚中不溶。用作囊材的用量为10~30g/L,亦可与明胶、CMC-Na、聚维酮(PVP)等配合作复合囊材。
(5)羟丙甲纤维素(HPMC)
冷水中能溶胀成澄清或微浑浊的胶体溶液,pH值4.0~8.0(1%溶液,25℃) ,无水乙醇、乙醚 或丙酮中几乎不溶。
3.合成高分子材料
有生物不降解的和生物降解的两类。
生物不降解、且不受pH影响的囊材有聚酰胺、硅橡胶等。
生物不降解、但可在一定pH条件下溶解的囊材有聚丙烯酸树脂类、聚乙烯醇等。
生物降解的材料:聚碳酸酯、聚氨基酸、聚乳酸(PLA)、乙交酯丙交酯共聚物(PLGA)、聚乳酸-聚乙二醇嵌段共聚物(PLA-PEG)ε-己内酯与丙交酯共聚物等。特点:无毒、成膜性好、化学稳定性高,可用于注射。
聚酯类是迄今研究最多、应用最广的生物降解的合成高分子,它们基本上都是羟基酸或其内酯的聚合物。
常用的羟基酸是乳酸(1actic acid)和羟基乙酸(glycolic acid)。乳酸缩合得到的聚酯称聚乳酸,用PLA表示,由羟基乙酸缩合得的聚酯称聚羟基乙酸,用PGA表示;由乳酸与羟基乙酸缩合而成的,用PLGA表示,亦可用PLG表示。有的共聚物经美国FDA批准,也作注射用微球、微囊以及组织埋植剂的载体材料。
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