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1. 发明授权

US07524981B2 Phospholipid derivatives and process for the production there 有权
标题翻译：磷脂衍生物及其生产工艺
公开(公告)号：US07524981B2
公开(公告)日：2009-04-28
申请号：US10541309
申请日：2003-12-12
申请人： Kazuhiro Kubo , Chika Itoh , Syunsuke Ohhashi , Tohru Yasukohchi , Yusuke Ohkawa , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
发明人： Kazuhiro Kubo , Chika Itoh , Syunsuke Ohhashi , Tohru Yasukohchi , Yusuke Ohkawa , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
IPC分类号： C07C9/02
CPC分类号： A61K9/127 , A61K8/14 , A61K8/553 , A61K9/0014 , A61K9/1273 , A61K47/24 , A61Q19/00 , C07F9/10 , C08G65/2609 , C08G65/3353 , C08G2650/34
摘要： A phospholipid derivative represented by the following formula (1): wherein [PG]k represents a residue of polyglycerin having a polymerization degree of k, wherein k is 2 to 50, R1CO and R2CO independently represent an acyl group having 8 to 22 carbon atoms, symbol “a” independently represents an integer of 0 to 5, symbol “b” independently represents 0 or 1, M represents hydrogen atom, an alkali metal atom, an ammonium, or an organic ammonium, and k1, k2, and k3 represent numbers satisfying the following conditions: 1≦k1≦(k+2)/2, 0≦k2, and k1+k2+k3=k+2. The phospholipid derivative is highly safe for living bodies and can be suitably utilized in drug delivery systems such as liposome, and the like.
摘要翻译：由下式（1）表示的磷脂衍生物：其中[PG] k表示聚合度为k的聚甘油的残基，其中k为2〜50，R1CO和R2CO独立地表示碳原子数为8〜22的酰基符号“a”独立地表示0〜5的整数，符号“b”独立地表示0或1，M表示氢原子，碱金属原子，铵或有机铵，k1，k2和k3表示满足以下条件的数字：1 <= k1 <=（k + 2）/ 2,0 <= k2，k1 + k2 + k3 = k + 2。磷脂衍生物对于活体是高度安全的，并且可以适用于药物递送系统如脂质体等。

2. 发明申请

US20060210618A1 Phospholipid derivatives and process for the production there 有权
标题翻译：磷脂衍生物及其生产工艺
公开(公告)号：US20060210618A1
公开(公告)日：2006-09-21
申请号：US10541309
申请日：2003-12-12
申请人： Kazuhiro Kubo , Chika Itoh , Syunsuke Ohhashi , Tohru Yasukohchi , Yusuke Ohkawa , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
发明人： Kazuhiro Kubo , Chika Itoh , Syunsuke Ohhashi , Tohru Yasukohchi , Yusuke Ohkawa , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
IPC分类号： A61K9/127 , C07F9/02 , A61K31/66
CPC分类号： A61K9/127 , A61K8/14 , A61K8/553 , A61K9/0014 , A61K9/1273 , A61K47/24 , A61Q19/00 , C07F9/10 , C08G65/2609 , C08G65/3353 , C08G2650/34
摘要： A phospholipid derivative represented by the following formula (1): wherein [PG]k represents a residue of polyglycerin having a polymerization degree of k, wherein k is 2 to 50, R1CO and R2CO independently represent an acyl group having 8 to 22 carbon atoms, symbol “a” independently represents an integer of 0 to 5, symbol “b” independently represents 0 or 1, M represents hydrogen atom, an alkali metal atom, an ammonium, or an organic ammonium, and k1, k2, and k3 represent numbers satisfying the following conditions: 1≦k1≦(k+2)/2, 0≦k2, and k1+k2+k3=k+2. The phospholipid derivative is highly safe for living bodies and can be suitably utilized in drug delivery systems such as liposome, and the like.
摘要翻译：由下式（1）表示的磷脂衍生物：其中[PG] k表示聚合度为k的聚甘油的残基，其中k为2至50，R 1 CO和R SUP > 2 CO独立地表示具有8至22个碳原子的酰基，符号“a”独立地表示0至5的整数，符号“b”独立地表示0或1，M表示氢原子，碱金属原子，铵或有机铵，k1，k2和k3表示满足以下条件的数：1 <= k1 <=（k + 2）/ 2,0 <= k2，k1 + k2 + k3 = k + 2。磷脂衍生物对于活体是高度安全的，并且可以适用于药物递送系统如脂质体等。

3. 发明授权

US07399877B2 Phospholipid derivative 有权
标题翻译：磷脂衍生物
公开(公告)号：US07399877B2
公开(公告)日：2008-07-15
申请号：US10549630
申请日：2004-03-19
申请人： Chika Itoh , Syunsuke Ohhashi , Kazuhiro Kubo , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
发明人： Chika Itoh , Syunsuke Ohhashi , Kazuhiro Kubo , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
IPC分类号： C07F9/02
CPC分类号： A61K9/127 , C07F9/10 , C11D1/345
摘要： A phospholipid derivative represented by the following formula (I) wherein R1CO and R2CO independently represent an acyl group; R3 represents hydrogen atom, or a hydrocarbon group; symbol “a” represents an integer of 0 to 4; symbol “b” represents 0 or 1, provided that when a is 0, b is 0; X represents hydrogen atom, an alkali metal atom, an ammonium, or an organic ammonium; A1O and A3O represent an oxyalkylene group containing oxyethylene group, wherein the ratio of the oxyethylene group to the oxyalkylene group in A1O and A3O is 0.5 or larger in terms of a weight ratio; A2O represents an oxyalkylene group; symbols “m” and “q” represent an average molar number of added oxyalkylene groups; and symbol “n” represent an average molar number of added oxyalkylene groups; provided that m, n and q satisfy the following conditions: 5≦m≦600, 1≦n≦45, 0≦q≦200, 10≦m+n+q≦600, 0.04≦n/(m+n+q), and q/(m+n+q)≦0.8, which can thicken the water shell of liposome surface by suppressing the spreading of the polyalkylene oxide structure on the surface and thus increase stability of the liposome
摘要翻译：由下式（I）表示的磷脂衍生物，其中R 1 CO和R 2 CO独立地表示酰基; R 3表示氢原子或烃基; 符号“a”表示0〜4的整数，符号“b”表示0或1，条件是当a为0时，b为0; X表示氢原子，碱金属原子，铵或有机铵; A 1 O和A 3 O表示含氧化乙烯基的氧化烯基，其中A 1 O 3中的氧乙烯基与氧化烯基的比例 O和A 3 O以重量比计为0.5以上; O 2表示氧化烯基; 符号“m”和“q”表示加成的氧化烯基团的平均摩尔数; 符号“n”表示加成的氧化烯基的平均摩尔数; 条件是m，n和q满足以下条件：5 <= m <= 600,1 <= n <= 45,0 <= q <= 200,10 <= m + n + q <= 600,0.04 < = n /（m + n + q）和q /（m + n + q）<= 0.8，这可以通过抑制聚环氧烷结构在表面上的扩散而增加脂质体表面的水壳，从而增加稳定性的脂质体

4. 发明授权

US07495116B2 Phospholipid derivative 有权
标题翻译：磷脂衍生物
公开(公告)号：US07495116B2
公开(公告)日：2009-02-24
申请号：US10508704
申请日：2003-03-28
申请人： Chika Itoh , Kazuhiro Kubo , Syunsuke Ohhashi , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
发明人： Chika Itoh , Kazuhiro Kubo , Syunsuke Ohhashi , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
IPC分类号： C07C9/02
CPC分类号： A61K47/24 , A61K8/14 , A61K8/553 , A61K8/556 , A61K8/86 , A61K9/1271 , A61Q19/00 , C07F9/10 , C08G65/2609 , C08G65/3353
摘要： A phospholipid derivative represented by the formula (1) (Z represents a residue of a compound having 3 to 10 hydroxyl groups; AO represents an oxyalkylene group having 2 to 4 carbon atoms; R1CO and R2CO represent an acyl group having 8 to 22 carbon atoms; X represents hydrogen atom, an alkali metal atom, ammonium or an organic ammonium; “a” represents an integer of 0 to 4; “b” represents 0 or 1; Q represents hydrogen atom or methyl group; m represents an average number of moles of the oxyalkylene group added; and m, k1, k2, and k3 are numbers satisfying the following conditions: 3≦m≦200, 9≦m×(k1+k2+k3)≦1000, 1≦k1≦2, 0≦k2≦9 and 0≦k3≦9, and 3≦k1+k2+k3≦10), which is highly safe for living bodies, and is suitably used for solubilization and dispersion of physiologically active substances and the like, or in the fields of drug delivery systems such as liposomes and cosmetics.
摘要翻译：由式（1）表示的磷脂衍生物（Z表示具有3〜10个羟基的化合物的残基; AO表示碳原子数2〜4的氧化烯基）; R1CO和R2CO表示碳原子数为8〜22的酰基 ; X表示氢原子，碱金属原子，铵或有机铵;“a”表示0〜4的整数，“b”表示0或1; Q表示氢原子或甲基; m表示氧化亚烷基的摩尔数; m，k1，k2和k3是满足以下条件的数：3 <= m <= 200,9 [= mx（k1 + k2 + k3）<= 1000,1 1 = <= 2，0 <= k2 <= 9，0 <= k3 <= 9，3 <= k1 + k2 + k3 = 10），对生物体来说安全性高，适用于溶解分散的生理活性物质等，或药物递送系统如脂质体和化妆品领域。

5. 发明申请

US20070031481A1 Phospolipid derivative 有权
标题翻译：磷脂衍生物
公开(公告)号：US20070031481A1
公开(公告)日：2007-02-08
申请号：US10549630
申请日：2004-03-19
申请人： Chika Itoh , Syunsuke Ohhashi , Kazuhiro Kubo , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
发明人： Chika Itoh , Syunsuke Ohhashi , Kazuhiro Kubo , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Takahashi , Hitoshi Yamauchi
IPC分类号： A61K9/127 , A61K31/685 , C07F9/02
CPC分类号： A61K9/127 , C07F9/10 , C11D1/345
摘要： A phospholipid derivative represented by the following formula (I) wherein R1CO and R2CO independently represent an acyl group; R3 represents hydrogen atom, or a hydrocarbon group; symbol “a” represents an integer of 0 to 4; symbol “b” represents 0 or 1, provided that when a is 0, b is 0; X represents hydrogen atom, an alkali metal atom, an ammonium, or an organic ammonium; A1O and A3O represent an oxyalkylene group containing oxyethylene group, wherein the ratio of the oxyethylene group to the oxyalkylene group in A1O and A3O is 0.5 or larger in terms of a weight ratio; A2O represents an oxyalkylene group; symbols “m” and “q” represent an average molar number of added oxyalkylene groups; and symbol “n” represent an average molar number of added oxyalkylene groups; provided that m, n and q satisfy the following conditions: 5≦m≦600, 1≦n≦45, 0≦q≦200, 10≦m+n+q≦600, 0.04≦n/(m+n+q), and q/(m+n+q)≦0.8, which can thicken the water shell of liposome surface by suppressing the spreading of the polyalkylene oxide structure on the surface and thus increase stability of the liposome.
摘要翻译：由下式（I）表示的磷脂衍生物，其中R 1 CO和R 2 CO独立地表示酰基; R 3表示氢原子或烃基; 符号“a”表示0〜4的整数，符号“b”表示0或1，条件是当a为0时，b为0; X表示氢原子，碱金属原子，铵或有机铵; A 1 O和A 3 O表示含氧化乙烯基的氧化烯基，其中A 1 O 3中的氧乙烯基与氧化烯基的比例 O和A 3 O以重量比计为0.5以上; O 2表示氧化烯基; 符号“m”和“q”表示加成的氧化烯基团的平均摩尔数; 符号“n”表示加成的氧化烯基的平均摩尔数; 条件是m，n和q满足以下条件：5 <= m <= 600,1 <= n <= 45,0 <= q <= 200,10 <= m + n + q <= 600,0.04 < = n /（m + n + q）和q /（m + n + q）<= 0.8，这可以通过抑制聚环氧烷结构在表面上的扩散而增加脂质体表面的水壳，从而增加稳定性的脂质体。

6. 发明申请

US20060110436A1 Phospholipid derivative 有权
标题翻译：磷脂衍生物
公开(公告)号：US20060110436A1
公开(公告)日：2006-05-25
申请号：US10529692
申请日：2003-09-30
申请人： Syunsuke Ohhashi , Kazuhiro Kubo , Chika Itoh , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Kurosawa , Hitoshi Yamauchi
发明人： Syunsuke Ohhashi , Kazuhiro Kubo , Chika Itoh , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Kurosawa , Hitoshi Yamauchi
IPC分类号： A61K31/795 , C08F291/00 , A61K9/127
CPC分类号： C08F8/40 , A61K8/14 , A61K8/8164 , A61K9/127 , A61K9/1271 , A61K9/1278 , A61K31/795 , A61Q19/00 , C08F220/28 , C08F222/06 , C08L53/00 , C08F222/04 , C08L2666/02
摘要： A phospholipid derivative, utilizable for modification of liposomes and the like, which is a copolymer containing, as essential component units, a component unit A represented by the formula (1), a component unit B represented by the formula (2A) and/or the formula (2B), and a component unit C represented by the formula (3) [R1 and R2 represent hydrogen atom or methyl group, provided that R1 and R2 do not simultaneously represent methyl group; R3 represents a divalent hydrocarbon group having 1 to 3 carbon atoms; AO represents an oxyalkylene group having 2 to 4 carbon atoms; m represents an average molar number of the added oxyalkylene groups and is a number in the range represented as 4≦m≦100; R4 represents hydrogen atom, a hydrocarbon group or acyl group having 1 to 20 carbon atoms; R5CO and R6CO represent an acyl group having 8 to 24 carbon atoms; R7 represents a divalent hydrocarbon group having 2 to 4 carbon atoms; and X and Y represent hydrogen atom, an alkali metal atom, ammonium or an organic ammonium] wherein a molar ratio of the component unit A relative to a total of the component unit B and the component unit C is from 7/3 to 3/7, and the component unit C is contained at a ratio of from 1 to 4 moles per 1 mole of the copolymer.
摘要翻译：可用于脂质体改性的磷脂衍生物等，其是以式（1）表示的成分单元A，式（2A）表示的成分单元B和/或式式（2B）和式（3）表示的成分单元C [R 1和R 2]表示氢原子或甲基，条件是R 0 > 1 和R 2不同时表示甲基; R 3表示具有1至3个碳原子的二价烃基; AO表示碳原子数2〜4的氧化烯基， m表示加成的氧化烯基的平均摩尔数，是在4≤M≤100的范围内的数字; R 4表示氢原子，碳原子数为1〜20的烃基或酰基， R 5 CO和R 6 CO表示具有8至24个碳原子的酰基; R 7表示具有2至4个碳原子的二价烃基; 并且X和Y表示氢原子，碱金属原子，铵或有机铵]，其中组分单元A相对于组分单元B和组分单元C的总量的摩尔比为7/3至3 / 7，组分单元C的含量相对于1摩尔共聚物为1〜4摩尔。

7. 发明授权

US07531604B2 Phospholipid derivative 有权
标题翻译：磷脂衍生物
公开(公告)号：US07531604B2
公开(公告)日：2009-05-12
申请号：US10529692
申请日：2003-09-30
申请人： Syunsuke Ohhashi , Kazuhiro Kubo , Chika Itoh , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Kurosawa , Hitoshi Yamauchi
发明人： Syunsuke Ohhashi , Kazuhiro Kubo , Chika Itoh , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Kurosawa , Hitoshi Yamauchi
IPC分类号： C08F8/32 , C08F8/40 , A61K9/127 , A61K47/32 , A61P35/00
CPC分类号： C08F8/40 , A61K8/14 , A61K8/8164 , A61K9/127 , A61K9/1271 , A61K9/1278 , A61K31/795 , A61Q19/00 , C08F220/28 , C08F222/06 , C08L53/00 , C08F222/04 , C08L2666/02
摘要： A phospholipid derivative, utilizable for modification of liposomes and the like, which is a copolymer containing, as essential component units, a component unit A represented by the formula (1), a component unit B represented by the formula (2A) and/or the formula (2B), and a component unit C represented by the formula (3) [R1 and R2 represent hydrogen atom or methyl group, provided that R1 and R2 do not simultaneously represent methyl group; R3 represents a divalent hydrocarbon group having 1 to 3 carbon atoms; AO represents an oxyalkylene group having 2 to 4 carbon atoms; m represents an average molar number of the added oxyalkylene groups and is a number in the range represented as 4≦m≦100; R4 represents hydrogen atom, a hydrocarbon group or acyl group having 1 to 20 carbon atoms; R5CO and R6CO represent an acyl group having 8 to 24 carbon atoms; R7 represents a divalent hydrocarbon group having 2 to 4 carbon atoms; and X and Y represent hydrogen atom, an alkali metal atom, ammonium or an organic ammonium] wherein a molar ratio of the component unit A relative to a total of the component unit B and the component unit C is from 7/3 to 3/7, and the component unit C is contained at a ratio of from 1 to 4 moles per 1 mole of the copolymer.
摘要翻译：可用于脂质体改性的磷脂衍生物等，其是以式（1）表示的成分单元A，式（2A）表示的成分单元B和/或式式（2B）和式（3）表示的成分单元C [R1和R2表示氢原子或甲基，条件是R1和R2不同时表示甲基; R3表示碳原子数为1〜3的二价烃基; AO表示碳原子数2〜4的氧化烯基， m表示加成的氧化烯基的平均摩尔数，为4≤m≤100的范围内的数; R4表示氢原子，碳原子数为1〜20的烃基或酰基， R5CO和R6CO表示碳原子数为8〜24的酰基， R 7表示碳原子数为2〜4的二价烃基; 并且X和Y表示氢原子，碱金属原子，铵或有机铵]，其中组分单元A相对于组分单元B和组分单元C的总量的摩尔比为7/3至3 / 7，组分单元C的含量相对于1摩尔共聚物为1〜4摩尔。

8. 发明申请

US20050220856A1 Phospholipid derivative 有权
标题翻译：磷脂衍生物
公开(公告)号：US20050220856A1
公开(公告)日：2005-10-06
申请号：US10508704
申请日：2003-03-28
申请人： Chika Itoh , Kazuhiro Kubo , Syunsuke Ohhashi , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Kurosawa , Hitoshi Yamauchi
发明人： Chika Itoh , Kazuhiro Kubo , Syunsuke Ohhashi , Tohru Yasukohchi , Hiroshi Kikuchi , Norio Suzuki , Miho Kurosawa , Hitoshi Yamauchi
IPC分类号： A61K8/14 , A61K8/55 , A61K8/86 , A61K9/127 , A61P35/00 , A61Q19/00 , C07F9/10 , C08G65/26 , C08G65/335 , C07F9/02
CPC分类号： A61K47/24 , A61K8/14 , A61K8/553 , A61K8/556 , A61K8/86 , A61K9/1271 , A61Q19/00 , C07F9/10 , C08G65/2609 , C08G65/3353
摘要： A phospholipid derivative represented by the formula (1) (Z represents a residue of a compound having 3 to 10 hydroxyl groups; AO represents an oxyalkylene group having 2 to 4 carbon atoms; R1CO and R2CO represent an acyl group having 8 to 22 carbon atoms; X represents hydrogen atom, an alkali metal atom, ammonium or an organic ammonium; “a” represents an integer of 0 to 4; “b” represents 0 or 1; Q represents hydrogen atom or methyl group; m represents an average number of moles of the oxyalkylene group added; and m, k1, k2, and k3 are numbers satisfying the following conditions: 3≦m≦200, 9≦m×(k1+k2+k3)≦1000, 1≦k1≦2, 0≦k2≦9 and 0≦k3≦9, and 3≦k1+k2+k3≦10), which is highly safe for living bodies, and is suitably used for solubilization and dispersion of physiologically active substances and the like, or in the fields of drug delivery systems such as liposomes and cosmetics.
摘要翻译：由式（1）表示的磷脂衍生物（Z表示具有3〜10个羟基的化合物的残基; AO表示碳原子数2〜4的氧化烯基，R 1，CO， SO 2表示碳原子数为8〜22的酰基，X表示氢原子，碱金属原子，铵或有机铵，“a”表示0〜4的整数，“b”表示 0或1; Q表示氢原子或甲基; m表示加入的氧化烯基的平均摩尔数; m，k1，k2和k3为满足以下条件的数：3 <= m <= 200,9 <= mx（k1 + k2 + k3）<= 1000,1 <= k1 <= 2,0 <= k2 <= 9，0 <= k3 = 9，3 <= k1 + k2 + k3 = 10 ），其对于活体是高度安全的，并且适合用于生理活性物质等的溶解和分散，或者在药物递送系统如脂质体和化妆品领域中。

9. 发明授权

US06679822B2 Polyalkylene oxide-modified phospholipid and production method thereof 有权
标题翻译：聚环氧烷改性磷脂及其制备方法
公开(公告)号：US06679822B2
公开(公告)日：2004-01-20
申请号：US10086430
申请日：2002-03-04
申请人： Kazuhiro Kubo , Chika Itoh , Syunsuke Ohhashi , Tohru Yasukohchi
发明人： Kazuhiro Kubo , Chika Itoh , Syunsuke Ohhashi , Tohru Yasukohchi
IPC分类号： C07F902
CPC分类号： C07F9/10 , A61K8/14 , A61K8/86 , A61Q19/00 , C08G65/3356
摘要： A polyalkylene oxide-modified phospholipid represented by formula (1) defined in the specification, has a monoacyl phospholipid content of not more than 3% by weight and a content of a base having a nitrogen atom of not more than 0.02% by weight.
摘要翻译：由说明书中定义的式（1）表示的聚环氧烷改性磷脂的单酰基磷脂含量不超过3重量％，氮原子含量不大于0.02重量％。

10. 发明授权

US07198945B2 Cell having modified cell membrane 有权
标题翻译：细胞具有改变的细胞膜
公开(公告)号：US07198945B2
公开(公告)日：2007-04-03
申请号：US10211587
申请日：2002-08-05
申请人： Teruyuki Nagamune , Chika Itoh , Tohru Yasukohchi , Syunsuke Ohhashi , Kazuhiro Kubo
发明人： Teruyuki Nagamune , Chika Itoh , Tohru Yasukohchi , Syunsuke Ohhashi , Kazuhiro Kubo
IPC分类号： C12N5/00
CPC分类号： C12N5/0006
摘要： A cell in which a reaction product of a substance to be modified and an amphipathic compound is non-covalently bound to a cell membrane, wherein said compound has the following features: (1) having one or more aliphatic hydrocarbon groups at one end; (2) having one or more portions containing a hydrophilic group in a molecule; and (3) having one or more reactive functional groups which are capable of covalently binding with the substance to be modified at an end different from the end in the above (1).
摘要翻译：其中待修饰物质和两亲性化合物的反应产物与细胞膜非共价结合的细胞，其中所述化合物具有以下特征

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