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1. 发明授权

US07141542B2 Method for stabilizing biomolecules in liquid formulations 有权
公开(公告)号：US07141542B2
公开(公告)日：2006-11-28
申请号：US10020799
申请日：2001-11-30
申请人： Siu Man L. Cowan , Vincent McGinniss , Donna T. Palmer , Steven M. Risser , Richard S. Brody
发明人： Siu Man L. Cowan , Vincent McGinniss , Donna T. Palmer , Steven M. Risser , Richard S. Brody
IPC分类号： A61K38/00 , A61K38/28 , A61K31/715
CPC分类号： A61K9/0078 , A61K9/0073 , A61K38/28 , A61K47/10 , A61K47/26
摘要： The invention is directed to a stable formulation of a biologically active protein useful for aerosol delivery to the respiratory tract of a patient in need of treatment comprising: (a) a carrier liquid comprising from about 10% to from about 100% V/V water and from about 0% to from about 90% V/V of an organic liquid; (b) a biologically effective amount of a protein suspended or dissolved in a carrier liquid; and (c) a stabilizing effective amount of a derivatized carbohydrate stabilizing agent suspended or dissolved in said carrier liquid. The stable formulations of the invention may optionally contain about 0.1% to about 5.0% W/V of a pharmaceutically acceptable excipient.

2. 发明授权

US5686262A Recycle process for the production of low-cost soluble collagen 失效
标题翻译：生产低成本可溶性胶原蛋白的回收工艺
公开(公告)号：US5686262A
公开(公告)日：1997-11-11
申请号：US488368
申请日：1995-06-07
申请人： David J. Fink , Richard S. Brody
发明人： David J. Fink , Richard S. Brody
IPC分类号： A61K38/00 , C07K14/78 , D21H11/14 , D21H17/22 , D21H21/18 , D21H17/00 , C12P21/00 , C12P21/06 , C07K3/12
CPC分类号： C07K14/78 , D21H17/22 , A61K38/00 , D21H11/14 , D21H21/18
摘要： The invention includes a method that provides a low cost aqueous solution of solubilized collagen by the steps of: (a) providing an aqueous ground slurry of insoluble collagen and adjusting the pH of said slurry to obtain activity for a proteolytic enzyme added in Step b; (b) adding said proteolytic enzyme to said pH adjusted slurry; (c) reacting the slurry and enzyme of Step b and/or recycled insoluble collagen and enzyme from Step e at a temperature, T, and for a time, t, effective for forming a solution increased in solubilized collagen; (d) adding additional water and insoluble collagen to said solution of Step c and mixing; (e) separating at least some of the solution of Step d containing solubilized collagen from insoluble collagen, whereby at least a portion of said insoluble collagen and proteolytic enzyme is recycled to Step c, and the separated solution containing solubilized collagen is withdrawn as product; an alternative embodiment provides for the direct production of solubilized collagen without the recycle step.
摘要翻译：本发明包括通过以下步骤提供低成本的溶解胶原水溶液的方法：（a）提供不溶性胶原的水性研磨浆液并调节所述浆液的pH以获得在步骤b中添加的蛋白水解酶的活性; （b）将所述蛋白水解酶加入到所述pH调节浆液中; （c）使步骤b的浆液和酶和/或来自步骤e的再循环不溶性胶原蛋白和酶在温度T下反应一段时间t，以有效形成溶解胶原中增加的溶液; （d）向步骤c的所述溶液中加入额外的水和不溶性胶原并混合; （e）将含有可溶化胶原蛋白的步骤d的至少一部分溶液从不溶性胶原中分离，由此将至少一部分所述不溶性胶原和蛋白水解酶再循环至步骤c，将含有溶解胶原的分离液作为产物取出; 替代实施例提供了直接生产溶解胶原蛋白而没有循环步骤。

3. 发明授权

US5460967A Recycle process for the production of low-cost soluble collagen 失效
标题翻译：生产低成本可溶性胶原蛋白的回收工艺
公开(公告)号：US5460967A
公开(公告)日：1995-10-24
申请号：US250803
申请日：1994-05-27
申请人： David J. Fink , Richard S. Brody
发明人： David J. Fink , Richard S. Brody
IPC分类号： A61K38/00 , C07K14/78 , D21H11/14 , D21H17/22 , D21H21/18 , C12P21/00 , C12N9/99
CPC分类号： C07K14/78 , D21H17/22 , A61K38/00 , D21H11/14 , D21H21/18
摘要： The invention includes a method that produces a low cost aqueous solution of solubilized collagen by the steps of: (a) providing an aqueous ground slurry of insoluble collagen and adjusting the pH of said slurry to obtain activity for a proteolytic enzyme added in Step b; (b) adding said proteolytic enzyme to said pH adjusted slurry; (c) reacting the slurry and enzyme of Step b and/or recycled insoluble collagen and enzyme from Step e at a temperature, T, and for a time, t, effective for forming a solution increased in solubilized collagen; (d) adding additional water and insoluble collagen to said solution of Step c and mixing; (e) separating at least some of the solution of Step d containing solubilized collagen from insoluble collagen, whereby at least a portion of said insoluble collagen and proteolytic enzyme is recycled to Step c, and the separated solution containing solubilized collagen is withdrawn as product; an alternative embodiment provides for the direct production of solubilized collagen without the recycle step.
摘要翻译：本发明包括通过以下步骤产生低成本的溶解胶原水溶液的方法：（a）提供不溶性胶原的水性研磨浆液并调节所述浆液的pH以获得在步骤b中添加的蛋白水解酶的活性; （b）将所述蛋白水解酶加入到所述pH调节浆液中; （c）使步骤b的浆液和酶和/或来自步骤e的再循环不溶性胶原蛋白和酶在温度T下反应一段时间t，以有效形成溶解胶原中增加的溶液; （d）向步骤c的所述溶液中加入额外的水和不溶性胶原并混合; （e）将含有可溶化胶原蛋白的步骤d的至少一部分溶液从不溶性胶原中分离，由此将至少一部分所述不溶性胶原和蛋白水解酶再循环至步骤c，将含有溶解胶原的分离液作为产物取出; 替代实施例提供了直接生产溶解胶原蛋白而没有循环步骤。

4. 发明授权

US5714042A Paper strengthened with solubilized collagen and method 失效
标题翻译：用增溶的胶原和方法增强纸张
公开(公告)号：US5714042A
公开(公告)日：1998-02-03
申请号：US483720
申请日：1995-06-07
申请人： Kenneth E. Hughes , David C. Masterson , David J. Fink , Barbara A. Metz , Gordon E. Pickett , Paul M. Gemmer , Richard S. Brody
发明人： Kenneth E. Hughes , David C. Masterson , David J. Fink , Barbara A. Metz , Gordon E. Pickett , Paul M. Gemmer , Richard S. Brody
IPC分类号： A61K38/00 , C07K14/78 , D21H11/14 , D21H17/22 , D21H21/18 , D21H17/00
CPC分类号： C07K14/78 , D21H17/22 , A61K38/00 , D21H11/14 , D21H21/18
摘要： A method for making a collagen strengthened cellulosic sheet by providing a cellulosic pulp slurry; adding solubilized collagen to the pulp slurry, and mixing for a time effective for interaction of the cellulosic pulp slurry and solubilized collagen; forming the interacted cellulosic pulp slurry and solubilized collagen into a sheet; and drying the sheet; also, a method for using solubilized collagen for strengthening paper by mixing the solubilized collagen with a cellulosic pulp slurry; and making a cellulosic pulp product from the mixture and drying.
摘要翻译：一种通过提供纤维素浆浆制备胶原增强的纤维素片的方法; 将溶解的胶原蛋白加入到纸浆中，并混合一段有效的纤维素浆浆和溶解胶原的相互作用的时间; 将相互作用的纤维素浆浆和溶解的胶原蛋白形成片; 并干燥片材; 还有，通过将溶解的胶原与纤维素浆浆混合来使用溶解的胶原来增强纸的方法; 并从混合物中制备纤维素纸浆产物并干燥。

5. 发明授权

US5700353A Paper strengthened with solubilized collagen and method 失效
标题翻译：用增溶的胶原和方法增强纸张
公开(公告)号：US5700353A
公开(公告)日：1997-12-23
申请号：US477856
申请日：1995-06-07
申请人： Kenneth E. Hughes , David C. Masterson , David J. Fink , Barbara A. Metz , Gordon E. Pickett , Paul M. Gemmer , Richard S. Brody
发明人： Kenneth E. Hughes , David C. Masterson , David J. Fink , Barbara A. Metz , Gordon E. Pickett , Paul M. Gemmer , Richard S. Brody
IPC分类号： A61K38/00 , C07K14/78 , D21H11/14 , D21H17/22 , D21H21/18 , D21H17/00
CPC分类号： C07K14/78 , D21H17/22 , A61K38/00 , D21H11/14 , D21H21/18
摘要： A method for making a collagen strengthened cellulosic sheet by providing a cellulosic pulp slurry; adding solubilized collagen to the pulp slurry, and mixing for a time effective for interaction of the cellulosic pulp slurry and solubilized collagen; forming the interacted cellulosic pulp slurry and solubilized collagen into a sheet; and drying the sheet; also, a method for using solubilized collagen for strengthening paper by mixing the solubilized collagen with a cellulosic pulp slurry; and making a cellulosic pulp product from the mixture and drying.
摘要翻译：一种通过提供纤维素浆浆制备胶原增强的纤维素片的方法; 将溶解的胶原蛋白加入到纸浆中，并混合一段有效的纤维素浆浆和溶解胶原的相互作用的时间; 将相互作用的纤维素浆浆和溶解的胶原蛋白形成片; 并干燥片材; 还有，通过将溶解的胶原与纤维素浆浆混合来使用溶解的胶原来增强纸的方法; 并从混合物中制备纤维素纸浆产物并干燥。

6. 发明授权

US06896894B2 Proteins stabilized with polysaccharide gums 失效
标题翻译：用多糖胶稳定的蛋白质
公开(公告)号：US06896894B2
公开(公告)日：2005-05-24
申请号：US10012667
申请日：2001-10-30
申请人： Richard S. Brody , Sreedhara Alavattam
发明人： Richard S. Brody , Sreedhara Alavattam
IPC分类号： A61K9/00 , A61K9/19 , A61K47/36 , A61F2/02
CPC分类号： A61K9/0024 , A61K9/19 , A61K47/36
摘要： Described are heat stable aqueous solutions or gels comprising a biologically effective amount of a protein and an effective stabilizing amount of a polysaccharide gum as well as heat stable solutions or gels suitable for use in an implantable drug delivery device at body temperature. Also disclosed are lyophilized compositions having biologically activity, where such lyophilized compositions are formed by lyophilizing the stabilized solutions or gels of the invention.
摘要翻译：描述了包含生物有效量的蛋白质和有效稳定量的多糖胶的热稳定水溶液或凝胶，以及适用于体温可植入药物递送装置的热稳定溶液或凝胶。还公开了具有生物活性的冻干组合物，其中通过冻干本发明的稳定化溶液或凝胶形成这种冻干组合物。

7. 发明授权

US5324524A Yeast derived mitogen 失效
标题翻译：酵母衍生有丝分裂原
公开(公告)号：US5324524A
公开(公告)日：1994-06-28
申请号：US695656
申请日：1991-05-06
申请人： Joyce M. Durnford , Richard S. Brody
发明人： Joyce M. Durnford , Richard S. Brody
IPC分类号： A61K36/06 , A61K38/00 , A61P43/00 , C07K14/395 , A61K35/72
CPC分类号： C07K14/395 , A61K38/00
摘要： A substantially pure mitogen is obtained from yeast. Medicaments containing the same and methods of treatment using the same are described.
摘要翻译：从酵母获得基本上纯的丝裂原。描述含有相同的药物和使用其的治疗方法。

8. 发明申请

US20080219951A1 Stabilization of Biologically Active Proteins With Mixtures of Polysaccharides and Amino Acid Based Compounds 审中-公开
标题翻译：用多糖和氨基酸化合物的混合物稳定生物活性蛋白质
公开(公告)号：US20080219951A1
公开(公告)日：2008-09-11
申请号：US11972023
申请日：2008-01-10
申请人： Richard S. Brody , Sreedhara Alavattam , William M. Fountain , Randy L. Jones
发明人： Richard S. Brody , Sreedhara Alavattam , William M. Fountain , Randy L. Jones
IPC分类号： A61K38/21 , A61K39/395 , A61K38/43 , A61K31/56 , A61K38/00 , A61K38/25
CPC分类号： A61K9/19 , A61K9/0024 , A61K38/212 , A61K38/217 , A61K38/443 , A61K38/4826 , A61K47/36
摘要： The invention provides heat stable aqueous solutions or gels comprising a biologically active protein and a stabilizing effective amount of a mixture of a polysaccharide and an amino acid based compound. The invention also discloses stabilized solutions or gels suitable for use in an implantable drug delivery device at body temperature, and a device containing the stabilized solution or gels.
摘要翻译：本发明提供了包含生物活性蛋白质和稳定有效量的多糖和基于氨基酸的化合物的混合物的热稳定水溶液或凝胶。本发明还公开了适用于体温可植入药物递送装置的稳定化溶液或凝胶，以及含有稳定化溶液或凝胶的装置。

9. 发明授权

US07060299B2 Biodegradable microparticles that stabilize and control the release of proteins 失效
标题翻译：稳定和控制蛋白质释放的可生物降解的微粒
公开(公告)号：US07060299B2
公开(公告)日：2006-06-13
申请号：US10750475
申请日：2003-12-31
申请人： Sreedhara Alavattam , Richard S. Brody
发明人： Sreedhara Alavattam , Richard S. Brody
IPC分类号： A61K9/64 , A61K9/22 , A61K9/14
CPC分类号： A61K9/1617 , A61K9/1647 , A61K9/1652 , A61K9/19
摘要： Disclosed herein are biodegradable microparticle compositions, and methods for the generation of biodegradable and biocompatible microparticles that stabilize proteins and also control the kinetics of release of proteins over a period of several weeks to several months under physiological conditions.
摘要翻译：本文公开了可生物降解的微粒组合物，以及用于产生稳定蛋白质的生物可降解和生物相容性微粒的方法，并且还在生理条件下在数周至数月的时间内控制蛋白质释放的动力学。

10. 发明授权

US5736010A Paper strengthened with solubilized collagen and method 失效
公开(公告)号：US5736010A
公开(公告)日：1998-04-07
申请号：US475486
申请日：1995-06-07
申请人： Kenneth E. Hughes , David C. Masterson , David J. Fink , Barbara A. Metz , Gordon E. Pickett , Paul M. Gemmer , Richard S. Brody
发明人： Kenneth E. Hughes , David C. Masterson , David J. Fink , Barbara A. Metz , Gordon E. Pickett , Paul M. Gemmer , Richard S. Brody
IPC分类号： A61K38/00 , C07K14/78 , D21H11/14 , D21H17/22 , D21H21/18 , D21H17/00
CPC分类号： C07K14/78 , D21H17/22 , A61K38/00 , D21H11/14 , D21H21/18
摘要： A method for making a collagen strengthened cellulosic sheet by providing a cellulosic pulp slurry; adding solubilized collagen to the pulp slurry, and mixing for a time effective for interaction of the cellulosic pulp slurry and solubilized collagen; forming the interacted cellulosic pulp slurry and solubilized collagen into a sheet; and drying the sheet; also, a method for using solubilized collagen for strengthening paper by mixing the solubilized collagen with a cellulosic pulp slurry; and making a cellulosic pulp product from the mixture and drying.

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