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1. 发明授权

US5962214A Method of preparing tissues and cells for vitrification 失效
标题翻译：制备组织和玻璃化细胞的方法
公开(公告)号：US5962214A
公开(公告)日：1999-10-05
申请号：US31893
申请日：1998-02-27
申请人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi , Thomas Maciag
发明人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi , Thomas Maciag
IPC分类号： A01N1/02
CPC分类号： A01N1/0247 , A01N1/02 , A01N1/0221
摘要： The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor .beta.1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor .beta.1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffi nose, sucrose, mannitol, etc.), medium (such as agents with intermediate molecular weights of around 600-2,000) and high (such as hydroxyethyl starch) molecular weight agents osmotic buffering agents. The invention is also directed to new post-transplantation treatments such as the use of transforming growth factor .beta.1, N-acetylcysteine and aurothioglucose.
摘要翻译：本发明涉及器官和组织灌注领域。更具体地，本发明涉及通过向其中引入可玻璃化浓度的冷冻保护剂来制备用于冷冻保存的器官如肾脏和肝脏的方法。为了制备用于低温保存的器官，供体人或动物以常规方式治疗，并且还可以用伊洛前列素或其它血管扩张剂和/或转化生长因子β1治疗。或者或另外，可以冷冻保存伊洛前列素或其他血管扩张剂，和/或将生长因子β1直接转化到其动脉中。本发明还涉及通过使用低（例如拉菲鼻，蔗糖，甘露醇等），培养基（例如中等分子量约600-2,000的试剂）从其中除去其中的冷冻保护剂的方法来制备移植器官，和高（如羟乙基淀粉）分子量试剂渗透缓冲剂。本发明还涉及新的移植后治疗，例如使用转化生长因子β1，N-乙酰半胱氨酸和嘌呤硫代葡萄糖。

2. 发明授权

US5723282A Method of preparing organs for vitrification 失效
标题翻译：玻璃化器官的制备方法
公开(公告)号：US5723282A
公开(公告)日：1998-03-03
申请号：US292001
申请日：1994-08-18
申请人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi , Thomas Maciag
发明人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi , Thomas Maciag
IPC分类号： A01N1/02
CPC分类号： A01N1/0247 , A01N1/02 , A01N1/0221
摘要： The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor .beta.1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor .beta.1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffinose, sucrose, mannitol, etc.), medium (such as agents with intermediate molecular weights of around 600-2,000) and high (such as hydroxyethyl starch) molecular weight agents osmotic buffering agents. The invention is also directed to new post-transplantation treatments such as the use of transforming growth factor .beta.1, N-acetylcysteine and aurothioglucose. Further, the invention relates to a method of vitrification of organs comprising a multi-step method of introducing increasing concentrations of cryoprotectant with osmotic equilibration of the organ and decreases in temperature prior to perfusion with vitrifiable concentrations of cryoprotectant at about -5.degree. C. to -35.degree. C.
摘要翻译：本发明涉及器官和组织灌注领域。更具体地，本发明涉及通过向其中引入可玻璃化浓度的冷冻保护剂来制备用于冷冻保存的器官如肾脏和肝脏的方法。为了制备用于低温保存的器官，供体人或动物以常规方式治疗，并且还可以用伊洛前列素或其它血管扩张剂和/或转化生长因子β1治疗。或者或另外，可以冷冻保存伊洛前列素或其他血管扩张剂，和/或将生长因子β1直接转化到其动脉中。本发明还涉及通过使用低（例如棉子糖，蔗糖，甘露醇等）的培养基（例如具有约600-2,000中等分子量的试剂）从其中除去冷冻保护剂的方法来制备用于移植的器官和高（如羟乙基淀粉）分子量试剂渗透缓冲剂。本发明还涉及新的移植后治疗，例如使用转化生长因子β1，N-乙酰半胱氨酸和嘌呤硫代葡萄糖。此外，本发明涉及一种器官玻璃化方法，其包括多步骤方法，其在器官的渗透平衡下引入增加浓度的冷冻保护剂，并在灌注之前温度降低，在约-5℃至可冷冻浓度的冷冻保护剂至 -35℃

3. 发明授权

US06187529B1 Method for preparing organs for transplantation after cryopreservation 失效
标题翻译：冷冻保存后移植器官的制备方法
公开(公告)号：US06187529B1
公开(公告)日：2001-02-13
申请号：US09066809
申请日：1998-04-28
申请人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi , Thomas Maciag
发明人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi , Thomas Maciag
IPC分类号： A01N102
CPC分类号： A01N1/0247 , A01N1/02 , A01N1/0221
摘要： The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor &bgr;1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor &bgr;1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffinose, sucrose, mannitol, etc.), medium (such as agents with intermediate molecular weights of around 600-2,000) and high (such as hydroxyethyl starch) molecular weight agents osmotic buffering agents. The invention is also directed to new post-transplantation treatments such as the use of transforming growth factor &bgr;1, N-acetylcysteine and aurothioglucose.
摘要翻译：本发明涉及器官和组织灌注领域。更具体地，本发明涉及通过向其中引入可玻璃化浓度的冷冻保护剂来制备用于冷冻保存的器官如肾脏和肝脏的方法。为了制备用于低温保存的器官，供体人或动物以常规方式治疗，也可以用伊洛前列素或其它血管扩张剂和/或转化生长因子β1进行治疗。或者或另外，待冷冻保存的器官可以给予伊洛前列素或其它血管扩张剂，和/或将生长因子β1直接转化入其动脉。本发明还涉及通过使用低（例如棉子糖，蔗糖，甘露醇等）的培养基（例如具有约600-2,000中等分子量的试剂）从其中除去冷冻保护剂的方法来制备用于移植的器官和高（如羟乙基淀粉）分子量试剂渗透缓冲剂。本发明还涉及新的移植后治疗，例如使用转化生长因子β1，N-乙酰半胱氨酸和嘌呤硫代葡萄糖。

4. 发明申请

US20050100876A1 Method of cryopreservation of tissues by vitrification 有权
标题翻译：通过玻璃化冷冻保存组织的方法
公开(公告)号：US20050100876A1
公开(公告)日：2005-05-12
申请号：US10646802
申请日：2003-08-25
申请人： Bijan Khirabadi , Ying Song , Kelvin Brockbank
发明人： Bijan Khirabadi , Ying Song , Kelvin Brockbank
IPC分类号： A01N1/02 , A61K35/12 , A61K35/44
CPC分类号： A01N1/02 , A01N1/0221 , A01N1/0284 , A61K35/44
摘要： A method for vitrification of a tissue or organ includes immersing the tissue or organ in increasing concentrations of cryoprotectant solution at a temperature greater than −15° C. to a cryoprotectant concentration sufficient for vitrification; cooling the tissue or organ at an average rate of from 2.5-100° C. per minute to a temperature between −80° C. and the glass transition temperature; and further cooling the tissue or organ at an average rate less than 30° C. per minute to a temperature below the glass transition temperature to vitrify the tissue or organ. After the vitrified tissue or organ has been stored, the tissue or organ may be removed from vitrification by warming the tissue or organ at an average rate of from 20-40° C. per minute to a temperature between −80° C. and the glass transition temperature; further warming the tissue or organ at a rate greater than 80° C. per minute to a temperature above −75° C.; and reducing the concentration of the cryoprotectant. Tissues or organs treated in this manner exhibit near normal functions, for example, blood vessels exhibit near normal smooth muscle contractility and normal graft functions.
摘要翻译：一种组织或器官的玻璃化方法包括将组织或器官在高于-15℃的温度下浸入浓度越来越高的冷冻保护剂浓度至足以进行玻璃化的冷冻保护剂浓度; 以2.5-100℃/分钟的平均速率将组织或器官冷却至-80℃和玻璃化转变温度之间的温度; 并且将组织或器官进一步以低于30℃/分钟的平均速率冷却到低于玻璃化转变温度的温度以使组织或器官玻璃化。在玻璃化组织或器官被储存之后，组织或器官可以通过将组织或器官以20-40℃/分钟的平均速率加热到-80℃和-80℃之间的温度而从玻璃化中除去玻璃化转变温度; 以大于80℃/分钟的速度将组织或器官进一步升温至-75℃以上的温度; 并降低冷冻保护剂的浓度。以这种方式处理的组织或器官表现出接近正常的功能，例如，血管表现出接近正常的平滑肌收缩和正常的移植功能。

5. 发明授权

US5821045A Methods for removal of cryoprotectant from organs prior to transplantation 失效
标题翻译：移植前从器官中除去冷冻保护剂的方法
公开(公告)号：US5821045A
公开(公告)日：1998-10-13
申请号：US455027
申请日：1995-05-31
申请人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi
发明人： Gregory M. Fahy , Bijan Khirabadi , Yasumitsu Okouchi
IPC分类号： A01N1/02
CPC分类号： A01N1/0247 , A01N1/02 , A01N1/0221
摘要： The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor .beta.1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor .beta.1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffinose, sucrose, mannitol, etc.), medium (such as agents with intermediate molecular weights of around 600-2,000) and high (such as hydroxyethyl starch) molecular weight agents osmotic buffering agents. The invention is also directed to new post-transplantation treatments such as the use of transforming growth factor .beta.1, N-acetylcysteine and aurothioglucose.
摘要翻译：本发明涉及器官和组织灌注领域。更具体地，本发明涉及通过向其中引入可玻璃化浓度的冷冻保护剂来制备用于冷冻保存的器官如肾脏和肝脏的方法。为了制备用于低温保存的器官，供体人或动物以常规方式治疗，并且还可以用伊洛前列素或其它血管扩张剂和/或转化生长因子β1治疗。或者或另外，可以冷冻保存伊洛前列素或其他血管扩张剂，和/或将生长因子β1直接转化到其动脉中。本发明还涉及通过使用低（例如棉子糖，蔗糖，甘露醇等）的培养基（例如具有约600-2,000中等分子量的试剂）从其中除去冷冻保护剂的方法来制备用于移植的器官和高（如羟乙基淀粉）分子量试剂渗透缓冲剂。本发明还涉及新的移植后治疗，例如使用转化生长因子β1，N-乙酰半胱氨酸和嘌呤硫代葡萄糖。

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