CN86105023A - 延长生长促进激素的释放 - Google Patents
延长生长促进激素的释放 Download PDFInfo
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- CN86105023A CN86105023A CN198686105023A CN86105023A CN86105023A CN 86105023 A CN86105023 A CN 86105023A CN 198686105023 A CN198686105023 A CN 198686105023A CN 86105023 A CN86105023 A CN 86105023A CN 86105023 A CN86105023 A CN 86105023A
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Classifications
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- 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
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A—HUMAN NECESSITIES
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- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
本发明涉及能在动物中延长生长激素的释放的生长激素配方。所述配方包含油赋形剂及有效量的生长激素的过渡金属络合物。本发明也涉及通过给动物服用所述生长促进配方来促进动物生长的方法。
Description
大量与动物服用生长激素相关的问题是所需要处理的次数问题,因而造成所需付出的劳动成本不断增长的结果。另外,供人类食用的动物,特别是如牛和羊等反类动物,都是在进行催膘饲养之前,在相当长的时间内是放牧饲养的。因此,导致通过注射服用激素显现其有可行性,从经济观点上来看也是不实际的。
在美国专利第4,333,919号中公开过一已知受控释放配方。该配方包含把生长激素与从基本上不含聚合反应催化剂的乳酸羟基乙酸衍生的共聚物混合。在此参考资料中公开的生长促进激素的实例包括聚酯如莫能菌素(monensin)、盐霉素(salinomycin)、拉沙里菌素(lasalocid)及相关的化合物。这些生长促进剂通过改变在动物的瘤胃中的食物的崩溃而起作用。因此,这些药剂须投置于动物的瘤胃或蜂窝瘤胃方为有效。证实这些生长促进药剂在促进生长方面是有效的,同时,往往需要给反动物服用具生理活性肽组合物,例如可进一步促进动物生长的激素。
遗憾的是,从来未知这些生长促进激素是属于导入动物的肠道内的受控释放配方或传送系统。因此,有要求提供给反类动物或其他动物用,能延长生长促进激素的释放的生长促进配方的需要是存在的。
本发明涉及供给动物用的延长生长激素的释放的生长促进配方。更具体说涉及关于生长促进配方,包含把油赋形剂与生长促进激素的过渡金属混合。生长激素的金属络合物较其以自由形式的生长激素本身的溶解度为低,因而在注射到动物体内就会有较慢的释放速度。
本发明提供的生长促进配方包含电赋形剂和有效量的生长促进激素的金属络合物。这配方容许在服用所述配方后可以在延长期内向动物传送有效剂量的生长促进剂。本发明的配方包含各种生长促进激素的过渡金属络合物。适宜的生长促进激素包括具生理活性多肽组合物,例如人类、牛类、马类、羊类、鸟类和猪类的生长促进激素。
本发明中所用的生长激素可用各种动物的脑下重体腺通过用提取法而后用浓缩技术而获取。用再生DNA方法生产的生长激素也是适宜的。已知有适宜于本发明的各种激素的氨基酸顺序。例如在“化学技术百科全书”第三版、第十二集、第549-552页,Kirk、Othmer出版社,C.H.Li叙述的论文中的人类生长促进激素的氨基酸顺序。在“核酸研究”第10期7197页(1982)R.P.Woyc-hik叙述的论文中的牛类生长激素的氨基酸顺序。在“生物化学和生物物理学公报”156期493-508页(1973)C.H刘等人叙述的论文中的羊类的生长激素的氨基酸顺序。在“脱氧核糖核酸(DNA)”第2期37.45页(1983)P.H.Seeburg等人叙述的论文中的猪类的生长激素的氨基酸顺序。上述叙述氨基酸顺序的参考资料以它们的整体内容结合到本发明而作为参考资料。除上述外,可通过从氧基酸的氨基末端删去直至12个氨基酸残基也可制造已改进生长激素的过渡金属络合物。
各种过渡金属均可与生长促进激素进行络合反应。这种金属包括有锌、铜、锰、钴、铁及其同类,以锌为最好。这些金属络合化通常是通过将生长促进激素和所述金属的水溶性形式在水溶液中进行混合而形成。该水溶性化合物包括有该金属的醋酸盐、硫酸盐、溴化物、甲酸盐、乳酸盐、丙酸盐、氯化物及其同类。一般说来,依赖于具体的生长促进激素而定,但每摩尔生长激素至少须有1摩尔、最好2摩尔或更多摩尔的过渡金属可供与该激素进行络合化反应。
生长促进激素的金属络合物是分散在增稠的油赋形剂中。如本专业的熟练技术人员所了解的,所述的油赋形剂必须是生物可容性。该油赋形剂提供传送金属激素络合物的载体同时动物服用后可抑制住由动物的体液中可能获取的各种络合物。能提供给本发明载体的油类有矿物油及包括下列但不为其所限定的诸如:花生油、芝麻籽油及黄豆油等植物油。由于生长激素的金属络合物通常为固体,因此须有充分数量的油以便把配方注射或通过如植入动物体内。通常油的量是由约90%至约99%该增稠油赋形剂的重量。而且以包含从约95%至约98%总配方的重量为最好。
除了油之外,亦可加入各种已知辅助剂或者赋形剂以便进一步延长络合着金属的生长激素的释放率。这种辅助剂包括蜂蜡、单硬酯酸铝、巴西扇棕、石蜡及其同类。这些附加物的数量,通常以总配方重量的约1%至约10%。上述辅助剂的存在以总配方的重量剃以约2%至约5%最好。特别好的增稠油赋形剂包括花生油和单硬酯酸铝的混合物和黄豆油和蜂蜡的混合物。
本发明提供的特别好的配方包括对实现促进反类动物或其他动物的生长的非常有用的可被生物降解的剂量形式,它包含按重量计从约50%至0.01%,最好为从约30%至约0.10%的锌络合的生长激素,该激素密切地分散在整个增稠油赋形剂中,该油赋剂包含按重量计从约90%至约99%的花生油和按重量计从约1%至约10%的单硬酯酸铝。
本发明还提供连续地实现促进动物的生长的方法,该方法包括给动物服用有效数量的延长释放配方。该配方由按重量计从约0.1%至约30%的过渡金属络合生长促进素与按重量计从约70%至约99.9%的增稠油赋形剂混合而成的而所述增稠油赋形剂则包含按重量计从约90%至约99%的植物油与按重量计从约1%至约10%的蜂蜡或单硬酯酸铝。按照本发明的方法,在动物服用所述配方后,动物可在一段延长的时间内接受连续有效剂量的生长促进激素。按照本发明的最好方法包括给动物服用有效量的配方,该配方包括按重量计从约10%至约0.5%的金属络合的生长促进激素与按重量计从约90%至约99.5%的增稠油赋剂混合。该增稠油赋形剂为包含按重量计从约95%至约98%的植物油与按重量计从约5%至约2%的蜂蜡或单硬酯酸铝的混合物所组成。
该生长促进配方可用若干方法服用。一个方法为注射。另一方法是借助植入药物的器械进行服用。已知有若干植入药物的器械可使用本发明的配方。植入药物的器械通常包含一泵或型片,通过它将贮液器中药物导入周围的组织中。当服用的方法是借助植入传送器械时,可选择除去使用油而只简单地使用过渡金属络合物。其他固体药物剂如前所述的赋形剂或辅助剂是可任意选择使用的。在这种情况下,过渡金属络合物的数量范围按重量计为固体生长促进配方的约50%至99.9%,而最好的范围为从约50%至80%。
下面提供说明本发明实例,但在任何情况下,不是也不可解释成为对本发明的限制。
实例1
生产猪类的生长激素一锌络合物。
在500毫升埃伦逐厄氏(Erlenmeyev)烧瓶中放置500毫克猪类生长激素(巴劳(Parlow)4640-c)和400毫升0.075N氯化钿溶液其PH已调整至7.在室温下将所述混合物搅拌24小时(磁搅拌器),而后以9000转/分的离心机离心旋转20分钟以分离小量不溶物质。将上清液从不溶物质(干燥后为60毫克)倾析,而后通过0.2薄膜滤器消毒之。
将该猪生长激素溶液放置于500毫升血清瓶中,并在磁搅拌条件下将20毫升无菌0.01M醋酸锌滴加,将混合物搅拌15分钟,以及用0.1N氢氧化钠调整PH至达7.4。将沉积物和溶液等分的转移到两个250毫升的离心瓶中并存放在温度为5℃的冰箱中过夜。将离心瓶中的物体再用转速为9000转分的离心机旋转离心20分钟,再把上清液倾析。把上清液分成两等份各装入500毫升的消血毒清瓶,壳层冷冻,并冷冻干燥两天得2.34克产品。将沉淀的锌络合的生长激素(ZnpGH)淤浆化在100毫升消毒的去离子水中,用9000转/分的离心机旋转离心20分钟,并从上清液中分离出来。将上液冷冻干燥得36.5毫克物质。把已洗涤的Zn PGH在室温条件下真空干燥给出0.290g产品。在Zn PGH中每摩尔PGH含有2.35摩尔锌,并发现与在hypox率生长测定中未络合化的猪类生长激素同样有活性。将所获2.34克盐溶解在10毫升的水中并用离心机离心。将所获得的上清液倾析,将沉淀物真空干燥,获得240毫克的固体。将各种分离出的固体用生物放射试验方法进行蛋白质分析,而用AA(原子吸收光谱)来分析锌含量。其结果列于表1中。
表1
分离出固体Zn PGH制品的成分
馏分说明 蛋白质重量 锌 平均重量增益
(生物放射) (%) 速度生长测定
290毫克Zn PGH 305.95±36.6 6998 21.2
36.5毫克从Zn PGH洗涤 9.22±3.87 2.84 22.7
240毫克从浓缩上清液 40.56±27 0.8674 11.9(无活性)
实例2
p GH-铜络合物
在磁搅拌的50毫升离心管中放置50毫克PGH(巴劳(p arl-oW)4640-C)及40毫升0.075M氯化钾该混合物在室温下搅拌24小时,而后用9000转/分旋转离心20分钟。上清液从不溶物(干燥后13.5毫克)中倾析、并将之与2毫升的0.01M醋酸铜。将反应混合物存放在5℃的冰箱中过夜,并用离心机分离铜的络合物。将络合物用10毫升水洗涤并在室温下真空干燥,产生27.8毫克铜-猪类生长激素络合物(CupPH)。借助AA测出CupGH中含有0.6043%铜,在速率生长测定中证实与未络合的p GH一样有活性,并借助生物放射测出含61.7%蛋白质。
实例3
用消毒的珀金斯-艾尔末(Perkin-Elmer)溴化钾药丸压制机在5000-6000磅压力下将ZnpGH(264毫克)压进1/2英寸药丸中。把药丸用消毒的研钵和槌捣碎成粉末,并用消毒的60-目筛节,产出202毫克细白色锌络合物。
在125毫升血清瓶中装进5克Mallin Ckrodt N.F.单硬酯酸铝和100毫升p lanter′s花生油(91.6克)。在热盘上用磁搅拌把混合物加热至150℃。并组持2小时。冷却至室温后,凝胶化的花生油用软膏刀搅拌,并把25毫升(22.34克)的混合物转送到50毫升的烧杯中。然后将200毫克60-目ZnpGH加到该花生油中,用3片SS-搅拌器以750转分搅拌所得上述混合物直至获得均匀悬浮液(15分钟)将一部分(5毫升)悬浮体抽进4个消毒的5毫升可随意使用的注射器中。将注射器存放在冷却设备里直至第2天。
实验4
动物研究
为证实本发明的配方的延长释放,4只重量各为120磅的阉猪注射5毫升按实例3中所述步骤制备的配方液。每个配方包含40毫升的锌络合的猪类生长激素。所述5毫升的配方是皮下注射到各猪的颈部。由猪的颈静脉抽取血样,并借助放射免疫测定法(RIA)分析其中生长的激素。在注射生长激素前已抽取血样供内部对照之用。表2列出根据抽血日期进行放射免疫测定的结果。
表2
猪中生长激素的血液浓度(毫微克/毫升)皮下注射ZnpGH配方后
1号猪 2号猪 3号猪 4号猪 (p GH)
注射前 -1 3.8 1.2 2.5 5.8 7.6±2.15
注射前 0 1.2 4.0 3.0 7.2 8.1±1.7
注射后 1 45.8 45.0 34.7 34.4 128±33.1
注射后 5 20.6 7.2 7.8 9.1 18.8±7.7
注射后 7 9.4 5.2 6.3 6.6 12.5±2.1
注射后 9 7.5 5.3 8.6 10.8 13.9±2.0
实例5
下列实例证实在给猪服用生长激素(p GH)后三个不同贮放系统的有效性。在服用各种配方之前,让九只阉猪适应圈养的条件,并使用列于下表的猪食料。
表3
饲料成分
项目 g
磨粉黄粟米 73.5
黄豆饲料-44% 23.5
磷酸二钙 1.2
石灰粉 0.8
盐 0.5
Dawes维生素预混料 0.5
100.0
计算成分(以-饲喂为基)
粗蛋白质 16.8
钙 0.62
磷 0.54
为比较一种金属络合的生长激素的有效性,使用了三个不同配方。配方1包含花生油及5%(重量/体积)单硬酯酸铝并含有8毫克/毫升的未络合的收巴劳(Parlow)猪类生长激素(批AFP-S324 C)的混合物。配方2包含黄豆油及4.5%(重量/体积)蜂蜡并含有8毫克/毫升的未络合的巴劳(Parlow)猪类生长激素(批AFP-S324 C)的混合物。配方3包含花生油及5%(重量/体积)单硬酯酸铝并含有8毫克/毫升ZnpGH的混合物。
两只猪在耳基处皮下注射5毫升化合物1。三只猪只以同样方式注射化合物2。四只猪也以同样方式注射化合物3。
定期地从各动物的前大静脉抽取20毫升血液。把血清样分离,并进行血清生长激素、血清尿氮(BUN)分析。
血液测定结果列于表4及表5中。
表4
在猪中BUN,p GH及葡萄糖浓度
在花生油单硬酯酸铝或黄豆油蜂蜡中服用非络合的p GH
平均值
化合物1 化合物2
p GH/花生 标准偏差 黄豆油 标准偏差
油单硬酯酸铝 蜂蜡
血清尿素氮(毫克/毫升)
0小时 11.41 (0.54) 13.33 (0.50)
3小时 13.49 (1.39) 14.46 (0.50)
6小时 11.79 (0.24) 13.21 (0.48)
24小时 4.33 (0.76) 5.63 (0.56)
2天 6.54 (1.18) 10.18 (2.03)
3天 7.55 (0.84) 9.45 (1.29)
7天 11.90 (0.73) 12.23 (0.86)
10天 9.69 (0.37) 10.16 (1.34)
15天 10.19 (1.16) 10.76 (0.68)
血清葡萄糖(毫克/毫升)
0小时 65.99 (12.39) 76.06 (9.52)
3小时 99.08 (3.03) 96.55 (6.89)
6小时 118.09 (13.60) 105.09 (6.74)
24小时 124.62 (10.14) 117.78 (4.82)
2天 93.13 (14.10) 94.74 (12.77)
3天 93.13 (5.59) 104.61 (11.09)
7天 102.85 (12.18) 99.27 (12.96)
10天 77.94 (7.18) 92.07 (4.78)
15天 85.91 (3.32) 91.73 (21.27)
血清生长激素(毫微克/毫升)
0小时 1.1* 3.7 (2.9)
3小时 76.1 (47.2) 64.5 (5.3)
6小时 97.5 (53.2) 93.0 (12.8)
24小时 84.6 (37.1) 57.9 (4.5)
2天 19.5 (3.5) 15.7 (2.8)
3天 14.4 (3.6) 7.3 (2.4)
7天 1.6 (0.3) 0.1*
*从一样品中得到的值
表5
猪中BUN、p GH及葡萄糖浓度
在花生油单体硬酯酸铝中服用ZnpGH
平均值
化合物3
ZnpGH/花生油单 标准偏差
硬酯酸铝
血清尿素氮(毫克/毫升):
-1天 12.63 (2.44)
0小时 9.30 (3.35)
24小时 7.19 (1.53)
5天 10.49 (3.41)
7天 10.71 (3.11)
9天 16.99 (4.56)
血清葡萄糖(毫克/毫升):
-1天 102.74 (4.52)
0小时 92.41 (7.28)
24小时 140.30 (4.64)
5天 99.10 (6.10)
7天 94.16 (11.70)
9天 125.22 (48.93)
血清生长激素(毫微克/毫升):
-1天 3.3 (2.0)
0小时 3.9 (2.5)
24小时 40.0 (6.3)
5天 11.2 (6.3)
7天 6.9 (1.8)
9天 8.1 (2.3)
上述表中的数据显示血清尿素氮浓度对三组动物是在注射后稍许下降,经7天后才恢复到0时值。葡萄糖浓度对三组动物在大多数血液样品中在第一天抽取最后血样时是高于未注射时的浓度。那些注射化合物1改化合物2的猪只在注射后3小时内血清p GH上升并在三天内一直保持在高的(超过底线值)浓度。那些服用锌络合的猪类生长激素的猪的血清浓度,在注射后也陡然上升,并在第9天的血清样品中发现仍然是高的。因此,用金属络合生长激素,如用锌在花生油/单硬酯酸铝的基质中络合生长激素增长了释放生长激素的时间,与未络合的生长激素释放时间相比,前者增长了200%,并显示对动物没有不利的影响。
Claims (18)
1、一种能延长生长促进激素释放的生长促进配方,其特征在于所述配方包括油赋形剂及有效量的生长促进激素的金属络合物。
2、一种能延长生长促进激素释放的生长促进配方,其特征在于所述配方饮食按重量计从约0.10%至约30%的生长促进激素的过渡金属络合物及按重量计从约70%至约99.9%的油赋形剂,该油赋形剂包括按重量计从约90%至99%选自包括矿物油。花生油、黄豆油及芝麻籽油及按重量计从约1%至10%辅助剂。
3、按权利要求2所述的配方,其特征在于其中所述辅助剂是选自包括蜂蜡、单硬酯酸铝、巴扇棕及石蜡的一组辅助剂。
4、延长生长促进激素的释放的配方,其特征在于其中所述配方包括按重量计从约10%至约0.5%的金属络合生长促进激素及按重量计从90%至约99.5%的增稠油赋形剂、该增稠油赋形剂包含按重量计从约95%至约98%的植物油及按重量计从约5%至约2%的蜂蜡或单硬酯酸铝。
5、按权利要求4要求的生长促进激素配方,其特征在于其中所述的生长促进激素是选自鸟类的、人类的、鸟类的、猪类的、羊类的或牛类的生长促进激素。
6、按权利要求5所述的生长促进激素配方,其特征在于其中所述的生长激素是猪的生长激素。
7、按权利要求4所述的生长促进配方,其特征在于其中所述的金属是选自包括锌、铜、锰、钴及铁的一组金属。
8、按权利要求7的生长促进激素配方,其特征在于其中所述的金属是锌。
9、一种生长促进组合物,其特征在于所述组合物包含生长促进激素的过渡金属络合物中所述生长促进激素是选自一组包括猪类的、羊类的、人类的、鸟类的、马类的及牛类的生长促进激素。
10、按权利要求9所述的生长促进组合物,其特征在于其中所述的金属是选自包括锌、铜、锰、钴及铁的一组金属。
11、按权利要求10所述的生长促进组合物,其特征在于其中所述激素是选自猪精、牛类的、马类的、人类的、鸟类的及羊类的生长激素。
12、按权利要求9所述的生长促进组合物,其特征在于其中所述的过渡金属络合物是与辅助剂混合。
13、按权利要求12所述的生长促进组合物,其特征在于其中所述的过渡金属是以辅助剂和过渡金属络合物的按总混合物的重量计从约50%至99.9%的量的情况存在在于组合物中。
14、按权利要求13所述的生长促进组合物,其特征在于其中所述的过渡金属是按重量计从约50%至约80%的量存在于组合物中。
15、连续地实现促进物生长的方法,其特征在于所述的方法包括给所述的动物服用有效量的按权利要求1所述的组合物。
16、一种连续地实现促进动物生长的方法,其特征在于所述的方法包括给所述的动物服用有效量的按权利要求2所述的组合物。
17、一种连续地实现促进动物生长的方法,其特征在于所述的方法包括给所述的动物服用有效量的按权利要求4所述的组合物。
18、一种连续地实现促进动物生长的方法,其特征在于所述的方法包括给所述的动物服用有效量的按权利要求9的组合物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US76440085A | 1985-08-12 | 1985-08-12 | |
US764,400 | 1985-08-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN86105023A true CN86105023A (zh) | 1988-02-24 |
Family
ID=25070628
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN198686105023A Pending CN86105023A (zh) | 1985-08-12 | 1986-08-12 | 延长生长促进激素的释放 |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP0216485A1 (zh) |
JP (1) | JPS6248635A (zh) |
KR (1) | KR870001825A (zh) |
CN (1) | CN86105023A (zh) |
AU (1) | AU596112B2 (zh) |
BR (1) | BR8603848A (zh) |
DK (1) | DK384286A (zh) |
ES (1) | ES2000864A6 (zh) |
IL (1) | IL79681A (zh) |
NZ (1) | NZ217175A (zh) |
PT (1) | PT83187B (zh) |
ZA (1) | ZA866052B (zh) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0343696B1 (en) * | 1984-10-04 | 1996-01-03 | Monsanto Company | Zinc-associated somatotropins |
ZA866218B (en) * | 1985-08-23 | 1988-03-30 | Lilly Co Eli | Injectable sustained release formulation |
CA1257199A (en) * | 1986-05-20 | 1989-07-11 | Paul Y. Wang | Preparation containing bioactive macromolecular substance for multi-months release in vivo |
EP0277043A3 (en) * | 1987-01-30 | 1989-08-23 | IMCERA Group Inc. | Method for recovering somatotropins from dilute aqueous solution |
US4863736A (en) * | 1987-03-16 | 1989-09-05 | Monsanto Company | Somatotropin prolonged release |
US5122512A (en) * | 1988-09-12 | 1992-06-16 | Pitman-Moore, Inc. | Swine growth promoting composition |
AU653325B2 (en) * | 1990-02-12 | 1994-09-29 | Lucky Limited | A composition durably releasing bioactive polypeptides |
US5780599A (en) * | 1990-07-13 | 1998-07-14 | Novo Nordisk A/S | Growth hormone crystals and a process for production of growth hormone crystals |
US6894023B1 (en) | 1990-07-13 | 2005-05-17 | Novo Nordisk A/S | Growth hormone crystals and a process for production of these GH-crystals |
DK168790D0 (zh) * | 1990-07-13 | 1990-07-13 | Novo Nordisk As | |
AU1757092A (en) * | 1991-03-28 | 1992-11-02 | Genentech Inc. | Stable growth hormone metal ion formulations |
YU87892A (sh) * | 1991-10-01 | 1995-12-04 | Eli Lilly And Company Lilly Corporate Center | Injektibilne formulacije produženog otpuštanja i postupci za njihovo dobijanje i primenu |
US6022858A (en) * | 1991-12-20 | 2000-02-08 | Novo Nordisk A/S | Pharmaceutical formulation of human-growth hormone pretreated with zinc salt |
US6087324A (en) * | 1993-06-24 | 2000-07-11 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
SE9303068D0 (sv) * | 1993-09-21 | 1993-09-21 | Kabi Pharmacia Ab | New use |
ATE197398T1 (de) * | 1994-09-09 | 2000-11-11 | Takeda Chemical Industries Ltd | Zubereitung mit verzögerter freigabe eines metallsalz eines peptids |
CA2224381A1 (en) | 1995-06-27 | 1997-01-16 | Takeda Chemical Industries, Ltd. | Method of producing sustained-release preparation |
US6191107B1 (en) | 1997-09-26 | 2001-02-20 | Takeda Chemical Industries, Ltd. | Complex of human growth hormone and zinc |
US6451347B1 (en) * | 1999-03-01 | 2002-09-17 | Alkermes Controlled Therapeutics, Inc. | Method for purifying human growth hormone |
KR20090007504A (ko) | 2000-02-24 | 2009-01-16 | 몬산토 테크놀로지 엘엘씨 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
ES2253375T3 (es) | 2000-04-19 | 2006-06-01 | Genentech, Inc. | Formulaciones de liberacion sostenida. |
AU2001271491A1 (en) | 2000-06-26 | 2002-01-08 | Monsanto Technology Llc | Non-aqueous surfactant-containing formulations for extended release of somatotropin |
US6664234B1 (en) | 2000-06-30 | 2003-12-16 | Monsanto Technology Llc | Non-aqueous injectable formulation preparation with pH adjusted for extended release of somatotropin |
TWI283182B (en) | 2000-08-07 | 2007-07-01 | Nektar Therapeutics | Inhalable spray dried 4-helix bundle protein powders having minimized aggregation |
EP1372729B1 (en) | 2001-02-23 | 2009-04-08 | Genentech, Inc. | Erodible polymers for injection |
IL159048A0 (en) * | 2001-06-21 | 2004-05-12 | Genentech Inc | Sustained release formulation |
NZ571243A (en) * | 2002-12-31 | 2010-04-30 | Altus Pharmaceuticals Inc | Complexes of protein crystals and ionic polymers comprising human growth hormone and protamine |
WO2004060310A2 (en) | 2002-12-31 | 2004-07-22 | Altus Pharmaceuticals Inc. | Human growth hormone crystals and methods for preparing them |
CN104017063A (zh) | 2009-12-21 | 2014-09-03 | Ambrx公司 | 经过修饰的猪促生长素多肽和其用途 |
EA201290541A1 (ru) | 2009-12-21 | 2013-05-30 | Амбркс, Инк. | Модифицированные бычьи соматотропиновые полипептиды и их применение |
JP6564369B2 (ja) | 2013-12-09 | 2019-08-21 | デュレクト コーポレイション | 薬学的活性剤複合体、ポリマー複合体、ならびにこれらを伴う組成物及び方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB885798A (en) * | 1958-12-06 | 1961-12-28 | Organon Labor Ltd | Preparations of the growth hormone |
DK100792C (da) * | 1961-05-23 | 1965-01-18 | Dumex Ltd As | Fremgangsmåde til fremstilling af et præparat med protraheret vitamin B12-virkning. |
DE2158123A1 (de) * | 1970-12-02 | 1972-06-08 | Ciba-Geigy Ag, Basel (Schweiz) | Neue pharmazeutische Präparate |
US4333919A (en) * | 1979-09-12 | 1982-06-08 | Eli Lilly And Company | Growth promotant controlled release formulations and method of treatment |
-
1986
- 1986-08-11 IL IL79681A patent/IL79681A/xx unknown
- 1986-08-12 KR KR1019860006617A patent/KR870001825A/ko not_active Application Discontinuation
- 1986-08-12 CN CN198686105023A patent/CN86105023A/zh active Pending
- 1986-08-12 NZ NZ217175A patent/NZ217175A/xx unknown
- 1986-08-12 ES ES8601040A patent/ES2000864A6/es not_active Expired
- 1986-08-12 BR BR8603848A patent/BR8603848A/pt unknown
- 1986-08-12 ZA ZA866052A patent/ZA866052B/xx unknown
- 1986-08-12 AU AU61092/86A patent/AU596112B2/en not_active Withdrawn - After Issue
- 1986-08-12 DK DK384286A patent/DK384286A/da not_active Application Discontinuation
- 1986-08-12 JP JP61187933A patent/JPS6248635A/ja active Pending
- 1986-08-12 EP EP86306237A patent/EP0216485A1/en not_active Ceased
- 1986-08-12 PT PT83187A patent/PT83187B/pt not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
AU596112B2 (en) | 1990-04-26 |
AU6109286A (en) | 1987-02-19 |
IL79681A0 (en) | 1986-11-30 |
NZ217175A (en) | 1989-11-28 |
ZA866052B (en) | 1987-03-25 |
KR870001825A (ko) | 1987-03-28 |
BR8603848A (pt) | 1987-03-24 |
EP0216485A1 (en) | 1987-04-01 |
ES2000864A6 (es) | 1988-03-16 |
DK384286D0 (da) | 1986-08-12 |
PT83187B (pt) | 1988-07-01 |
DK384286A (da) | 1987-02-13 |
PT83187A (en) | 1986-09-01 |
JPS6248635A (ja) | 1987-03-03 |
IL79681A (en) | 1991-06-10 |
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