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(self orientation method and composition of mother Mason chiama)

机译:(母亲梅森·奇亚玛的自我定位方法和组成)

摘要

Transmission refers to the method and composition of self-contained plateau stem cells (MSCs). The components include the compounds described in this application, which can guide MCC to express cell surface self-directed adhesion molecules, such as CD11a, and help MCC to adhere more firmly in the test tube section flow test, 1. To increase the binding with e-selectina or ICAM-1, and / or to show anti-inflammatory activity through in vivo system management of cell therapy using human MSCs. Besides,In order to find out the small molecular compounds and enhance the self conducting function of MSC, a systematic detection method was introduced. 1. Claim 1: methods for treating patients with injuries and injuries, including (a) the stages of providing high altitude stem cells (MSc);(b) Sanitary and phytosanitary measures are in contact with an effective number of compounds, including compounds (1) in the formula,so as to generate a composition comprising pretreated MSC, where the compound is capable of enhancing a self-steering function in pretreated MSC relative to that of untreated MSC, where said contact optionally includes incubation of the MSC with the compound composition; and (b) optionally, washing the pretreated MSCs; (c) administering an effective amount of the composition comprising pretreated MSCs, to the subject; where the compound has the structure of the formula (1) where: R¹ is selected from the series consisting of hydrogen, C₁₋₄-alkyl, phenyl-C₁₋₄-alkyl- and heteroaryl-C₁₋₄-alkyl-,where phenyl and heteroaryl are unsubstituted or substituted with substituents of the series consisting of halogen, C₁₋₄-alkyl and C₁₋₄-alkyl-O-;R2 and R3 are independently selected,e. In the halogen series, c83218331;R⁴ is selected from the series consisting of hydrogen and C₁₋₄-alkyl; R¹⁰ is selected from the series consisting of hydrogen, C₁₋₆-alkyl and Het¹,where C₁₋₆-alkyl is unsubstituted or substituted with R²⁰,Where hete1 has not been replaced or replaced by R2,R¹¹ is selected from the series consisting of hydrogen and C₁₋₄-alkyl, or R¹⁰ and R¹¹ together are a divalent group selected from the series consisting of the groups - (CH₂) ₘ-C (R²²) (R²³) - ( CH₂) ₙ- and - (CH₂) ₙ-N (R²⁴) - (CH₂) ₙ-,where the (CH₂) ₘ and (CH₂) restos residues are unsubstituted or substituted with C₁₋₄-alkyl; R²⁰ is selected from the series consisting of R³⁰-O-,R³¹-N (R³²) -,H N-C (3DNH) -S-Billy Dini and Hutt3. Het 'was not replaced by three cubic meters;R: 1 from c832131;where phenyl and pyridinyl are unsubstituted or substituted with substituents of the series consisting of halogen, C₁₋₄-alkyl and C₁₋₄-alkyl-O-;R²² is selected from the series consisting of hydrogen and C₁₋₄-alkyl; R²³ is selected from the series consisting of hydrogen, C₁₋₄-alkyl, R³¹-N (R³²) - and R³¹-N (R³²) -C₁₋₄-alkyl-;R se selecciona de la serie que consiste en hidr geno C -alquilo piridinilo-C -alquilo- y R -N (R) -C -alquilo-R³⁰,R³¹ and R³² are selected, independently of each other,from the series consisting of hydrogen and C₁₋₄-alkyl; R³³ is selected from the series consisting of C₁₋₄-alkyl; Het¹ is a saturated monocyclic 4- to 7-membered heterocycle, comprising a ring nitrogen atom, which is bonded via a ring carbon atom; Het² is a saturated monocyclic, 4- to 7-membered heterocycle comprising one or two ring nitrogen atoms, which is bonded via a ring carbon atom or a ring nitrogen atom; heteroaryl is a 5-membered or 6-membered heterocyclic, monocyclic, aromatic,It consists of one or two identical or different ring atoms selected from the N, O and S series; a and B are selected independently from each other,In the series of 0, 1 and 2, m and N are selected independently,A series of 1 and 2. Claim 8: the method of claim 1, wherein the composite method of item (1),The chemical name of the compound is 3 - (8-carbamate-6, 7, 8, 9-tetrahydro-pyridine [1, 2-A] india-10-il) - 4 - (1-methyl-1h-india-3-il) - Pyridine-2, 5-dioxy; the formula structure of the compound is (2). Claim 19: a compound composed of an in vitro purified MSc and an effective number of compounds, as described in the present application, which can enhance the self directing function of the MSC,The compound can be selected from formula (1) or any formula (2) to (20). Requirement 20: a system determination method for identifying a small molecular compound, which can improve a selective MSc function, including all stages: (a) providing candidate components including small molecular candidate components; (b) providing MSc; (c) How to deal with sanitary and phytosanitary measures and make them have candidate components to produce treated sanitary and phytosanitary measures; (d) how to measure the characteristics of treated sanitary and phytosanitary measures;This characteristic includes the expression of one or more cell surface molecules in vitro, which can promote the self-directed function, the in vitro adhesion with no visible effect concentration treated in the slice flow test, and the anti-inflammatory activity managed by the in vivo system in the animal inflammatory model; (e) Compare one or more sanitary and phytosanitary characteristics to a negative control sanitary and phytosanitary characteristic, in which the negative control sanitary and phytosanitary measures are not treated or treated, while the negative control candidate components cannot enhance the self-management function of sanitary and phytosanitary measures;Y (f) recognizes small molecular compounds, which can enhance the self directing function of MSC. In this function, the compounds of small molecules treated in the negative control of MSC show higher performance of one or more cell surface molecules that can provide one self directing function, In the section flow test, the in vitro adhesion was increased, the activity of autoimmune disease was reduced in the animal model of in vivo system management, and the anti-inflammatory activity of in vivo system management was increased in the animal model of inflammation. Requirement 24: a purified MSc in vitro culture,Among them, Morgan Stanley Capital International said that the cell area of CD11a is higher than that of the planted Morgan Stanley Capital International, whose largest cell area is endogenous and not designed. 13. Claim 27: a method for the development of therapeutic components of pre-treatment sanitary and phytosanitary products capable of enhancing self-management functions, including: (a) the provision of sanitary and phytosanitary products at all stages of the population; (b) The MSc is explained by contacting the MSc composed of the compound in the application, in which the compound can enhance the self directing function of the MSc; in the compound,The alternative is formula (1) or any formula (2) to (20),The self directing function is: (1) to enhance the expression ability of cell surface molecules, so that they can play the self directing function, in which the cell surface molecules are CD11a optionally; (2) to enhance the viscosity of MSC to the test tube in the slice flow test, (III) enhance the combination of e-selectina or ICAM-1, and (IV) increase the self-directed and / or anti-inflammatory activities of sanitary and phytosanitary measures in combination with the in vivo system management of sanitary and phytosanitary measures in animal models of inflammation, (c) prepare single dose or multi dose arias, (d) Optionally,3. Freeze the pre-treatment sanitary and phytosanitary measures to produce the pre-treatment sanitary and phytosanitary measures and thus the therapeutic components of the pre-treatment sanitary and phytosanitary measures.
机译:传播是指自足的高原干细胞(MSCs)的方法和组成。这些成分包括本申请中描述的化合物,它们可以引导MCC表达细胞表面自定向粘附分子,例如CD11a,并帮助MCC在试管截面流量测试中更牢固地粘附,1。 e-selectina或ICAM-1,和/或通过使用人MSC的细胞治疗的体内系统管理显示抗炎活性。此外,为了发现小分子化合物并增强MSC的自传导功能,介绍了一种系统的检测方法。 1.权利要求1:治疗受伤和受伤患者的方法,包括(a)提供高海拔干细胞(MSc)的阶段;(b)卫生和植物检疫措施与有效数量的化合物接触,包括化合物( 1)在式中,以产生包含预处理的MSC的组合物,其中该化合物能够相对于未处理的MSC增强在预处理的MSC中的自转向功能,其中所述接触任选地包括将MSC与化合物一起孵育组成; (b)任选地,洗涤预处理的MSC; (c)对受试者施用有效量的包含预处理的MSC的组合物;其中化合物具有式(1)的结构,其中:R 1选自氢,C 1-烷基,苯基-C 1-烷基-和杂芳基-C 4-烷基-,其中苯基杂芳基和杂芳基未被取代或被卤素,C 1-8烷基和C 1-6烷基-O-组成的系列的取代基取代; R 2和R 3独立地选自,e。在卤素系列中,c83218331; R 5选自氢和C 1-烷基; R 15选自氢,C 1-4烷基和Het -1,其中C 1-6烷基未被取代或被R 254取代,其中hete1未被R 2取代或未被R 2取代,R 1-1选自下组:氢和C 1-4烷基,或R 15和R 11一起是选自以下基团的二价基团:(CH 2)ₘ-C(R 22)(R 223)-(CH 2)ₙ-和-(CH 2)consisting -N(R 20)-(CH 2)3-,其中(CH 2)3和(CH 2)restos残基未被取代或被C 1-烷基取代; R 30选自R 33 -O-,R 31 -N(R 32)-,H N-C(3DNH)-S-Billy Dini和Hutt3。 Het′没有被三立方米取代; R:c832131的R;其中苯基和吡啶基未被取代或被卤素,C 1-4烷基和C 1-4烷基-O-组成的系列取代基取代; R 22是选自氢和C 1-4烷基的序列; R 23选自氢,C 1-4烷基,R 1-3 -N(R 322)-和R 1-3 -N(R 322)-C 1-6烷基; R s选自热C。 -alquilo piridinilo -C -al基-R -N(R)-C -alquilo-R 30,R 31和R 32彼此独立地选自氢和C 1-4烷基; R 3-选自C 1-烷基; Het 1是饱和的单环4至7元杂环,其包含通过环碳原子键合的环氮原子; Het 2是包含一个或两个环氮原子的饱和单环,4至7元杂环,其通过环碳原子或环氮原子键合;杂芳基是5元或6元杂环,单环,芳族,它由一个或两个选自N,O和S系列的相同或不同的环原子组成; a和B彼此独立地选择;在0、1和2系列中,m和N独立地选择; 1和2系列。权利要求8:权利要求1的方法,其中, 1),该化合物的化学名称为3-(8-氨基甲酸酯-6、7、8、9-四氢吡啶[1,2-A]印度-10-il)-4-(1-甲基-1h -india-3-il)-吡啶-2,5-二氧基;该化合物的分子式为(2)。 19.如权利要求19所述的化合物,其由体外纯化的MSc和有效数量的化合物组成,如本申请所述,其可以增强MSC的自指导功能,所述化合物可以选自式(1)或任何式(2)至(20)。要求20:一种鉴定小分子化合物的系统确定方法,其可以改善选择性的MSc功能,包括所有阶段:(a)提供包括小分子候选组分的候选组分; (b)提供理学硕士; (c)如何处理卫生和植物检疫措施并使之具有产生经处理的卫生和植物检疫措施的候选成分; (d)如何测量经处理的卫生和植物检疫措施的特征;该特征包括在体外表达一种或多种细胞表面分子,这些分子可以促进自我指导的功能,在体外没有明显的作用浓度的粘附切片流动测试以及在动物炎症模型中由体内系统管理的抗炎活性; (e)将一项或多项卫生和植物检疫特性与阴性对照的卫生和植物检疫特性进行比较,在阴性对照的卫生和植物检疫特性中,未处理或未处理阴性对照的卫生和植物检疫措施,而阴性对照的候选成分不能增强卫生的自我管理功能Y(f)识别能够增强MSC自我指导功能的小分子化合物。在此功能中,在MSC阴性对照中处理的小分子化合物表现出一种或多种可提供一种自指导功能的细胞表面分子的更高性能。在切片流动试验中,体外粘附力增加,在体内动物系统管理的动物模型中,自身免疫性疾病减少,并且在动物动物模型中的体内系统管理的抗炎活性增加。要求24:纯化的MSc体外培养,其中,摩根士丹利资本国际公司说CD11a的细胞面积比已种植的摩根士丹利资本国际公司的细胞面积高,后者的最大细胞面积是内源性的,未经设计。 13.权利要求27:开发能够增强自我管理功能的预处理的卫生和植物检疫产品的治疗成分的方法,包括:(a)在人口的各个阶段提供卫生和植物检疫产品; (b)在本申请中通过与由化合物组成的MSc接触来解释MSc,其中该化合物可以增强MSc的自指导功能;在该化合物中,可以是式(1)或任何式(2)至(20)的替代物,其自我指导功能是:(1)增强细胞表面分子的表达能力,使其可以发挥自我指导功能,其中细胞表面分子任选为CD11a; (2)在切片流动测试中提高MSC对试管的粘度,(III)增强e-选择素或ICAM-1的组合,和(IV)增加自我导向和/或抗炎活性卫生和植物检疫措施与体内炎症动物模型的体内系统管理相结合,(c)准备单剂量或多剂量咏叹调,(d)可选,3。冻结预处理卫生和植物检疫措施,以生产预处理卫生和植物检疫措施,从而生产预处理卫生和植物检疫措施的治疗成分。

著录项

  • 公开/公告号AR099146A1

    专利类型

  • 公开/公告日2016-07-06

    原文格式PDF

  • 申请/专利号AR2015P100160

  • 发明设计人

    申请日2015-01-21

  • 分类号A61P29;A61K31/4025;A61K31/404;A61K35/28;A61P37;

  • 国家 AR

  • 入库时间 2022-08-21 14:27:35

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