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1. 发明申请

WO2012170952A2 COMPOUNDS FOR TARGETING DRUG DELIVERY AND ENHANCING SIRNA ACTIVITY 审中-公开
标题翻译：用于靶向药物递送和增强SIRNA活性的化合物
公开(公告)号：WO2012170952A2
公开(公告)日：2012-12-13
申请号：PCT/US2012/041753
申请日：2012-06-08
申请人： NITTO DENKO CORPORATION , NIITSU, Yoshiro , PAYNE, Joseph E. , HOU, Zheng , GAUDETTE, John A. , NAGARAJAN, Sridhar C. , KNOPOV, Victor , WITTE, Richard P. , AHMADIAN, Mohammad , PERELMAN, Loren A. , TANAKA, Yasunobu , AKOPIAN, Violetta , KARMALI, Priya
发明人： NIITSU, Yoshiro , PAYNE, Joseph E. , HOU, Zheng , GAUDETTE, John A. , NAGARAJAN, Sridhar C. , KNOPOV, Victor , WITTE, Richard P. , AHMADIAN, Mohammad , PERELMAN, Loren A. , TANAKA, Yasunobu , AKOPIAN, Violetta , KARMALI, Priya
IPC分类号： C07C237/08 , A61K31/16 , A61P1/16 , C07C237/22 , C07C323/60 , C07C333/04
CPC分类号： C07C237/08 , A61K9/1271 , C07C237/22 , C07C323/60 , C07C333/04
摘要： Here described are compounds of formula I: wherein R 1 and R 2 is independently selected from a group consisting of C 10 to C 18 alkyl, C 12 to C 18 alkenyl, and oleyl group; wherein R 3 and R 4 are independently selected from a group consisting of C 1 to C 6 alkyl, and C 2 to C 6 alkanol; wherein X is selected from a group consisting of -CH 2 -, -S-, and -O- or absent; wherein Y is selected from -(CH 2 )n, -S(CH 2 ) n , -O(CH 2 ) n -, thiophene, -SO 2 (CH 2 ) n -, and ester, wherein n = 1 -4; wherein a = 1 -4; wherein b=l -4; wherein c=l-4; and wherein Z is a counterion; and compounds consisting of the structure (targeting molecule) m -linker-(targeting molecule) n , wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including one or both of these compounds which are useful for the delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.
摘要翻译：这里描述的是式I化合物：其中R 1和R 2独立地选自C 10至C 18烷基，C 12至C 18烯基和油基; 其中R3和R4独立地选自C1-C6烷基和C2-C6链烷醇; 其中X选自-CH 2 - ， - S-和-O-或不存在; 其中Y选自 - （CH 2）n，-S（CH 2）n，-O（CH 2）n - ，噻吩，-SO 2（CH 2）n - 和酯，其中n = 1-4; 其中a = 1-4; 其中b = 1-4; 其中c = 1-4; 并且其中Z是抗衡离子; 以及由结构（靶向分子）m-接头（靶向分子）n组成的化合物，其中靶向分子是靶细胞上具有特异性受体的类视黄醇或脂溶性维生素; 其中m和n独立地为0,1,2或3; 并且其中所述接头包含聚乙二醇（PEG）或PEG样分子，以及包含这些化合物中的一种或两种可用于递送治疗剂的组合物和药物制剂; 以及使用这些组合物和药物制剂的方法。

2. 发明申请

WO2012170957A3 RETINOID-LIPOSOMES FOR ENHANCING MODULATION OF HSP47 EXPRESSION 审中-公开
标题翻译：维甲酸 - 脂质体用于增强HSP47表达的调节
公开(公告)号：WO2012170957A3
公开(公告)日：2013-04-11
申请号：PCT/US2012041761
申请日：2012-06-08
申请人： NITTO DENKO CORP , QUARK PHARMACEUTICALS INC , NNTSU YOSHIRO , PAYNE JOSEPH E , KNOPOV VICTOR , AKOPIAN VIO ETTA , W TTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , FEINSTEIN ELENA , AVK N-NAHUM SHARON , KAL NSKI HAGAR , METT IGOR , MINOMI KENJIRO , Y NG WENBIN , LUI YUN
发明人： NNTSU YOSHIRO , PAYNE JOSEPH E , KNOPOV VICTOR , AKOPIAN VIO ETTA , W TTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , FEINSTEIN ELENA , AVK N-NAHUM SHARON , KAL NSKI HAGAR , METT IGOR , MINOMI KENJIRO , Y NG WENBIN , LUI YUN
IPC分类号： C12N15/113 , A61K31/713 , C12N15/11
CPC分类号： A61K9/1271 , A61K9/127 , A61K31/713 , C07H21/02 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/14 , C12N2320/32 , C12N2320/52
摘要： What is described are pharmaceutical compositions comprising a double-stranded nucleic acid molecule comprising a sense strand and an antisense strand wherein the sense and antisense strands are selected from the oligonucleotides described as SERPINH1_2 (SEQ ID NOS: 60 and 127), SERPTNHl_45a (SEQ ID NOS: 98 and 165), and SERPTNH1_51 (SEQ ID NOS: 101 and 168), and drug carrier comprising a mixture of a retinoid and a lipid vesicle, and methods of using these pharmaceutical compositions to treat a disease associated with hsp47 espresssion, including fibrosis.
摘要翻译：所描述的是包含双链核酸分子的药物组合物，所述双链核酸分子包含有义链和反义链，其中有义链和反义链选自描述为SERPINH1_2（SEQ ID NOS：60和127），SERPTNH1_45a（SEQ ID NO： NOS：98和165）和SERPTNH1_51（SEQ ID NOS：101和168），以及包含类视色素和脂质囊泡混合物的药物载体，以及使用这些药物组合物治疗与hsp47表达相关的疾病的方法，包括纤维化。

3. 发明申请

WO0105373A9 METHODS AND APPARATUS FOR PREPARATION OF LIPID VESICLES 审中-公开
标题翻译：用于制备脂质体的方法和装置
公开(公告)号：WO0105373A9
公开(公告)日：2002-08-29
申请号：PCT/CA0000842
申请日：2000-07-14
申请人： INEX PHARMACEUTICALS CORP , KNOPOV VICTOR , DZUBANOV KIRILL , HARPER KEVIN , CULLIS PIETER R
发明人： KNOPOV VICTOR , DZUBANOV KIRILL , HARPER KEVIN , CULLIS PIETER R
IPC分类号： A61J3/07 , A61K9/127 , A61K9/133 , A61K31/7125 , A61K45/00 , A61K47/10 , A61K47/12 , A61K47/16 , A61K47/18 , A61K47/24 , A61K47/28 , A61K48/00
CPC分类号： A61K9/1278 , A61K9/1272 , A61K9/1277
摘要： Improved production of lipid vesicles is achieved using an apparatus for preparation of a lipid vesicle that includes: (a) a first reservoir for receiving a buffer composition; (b) a static mixer for agitating buffer composition in the first reservoir; (c) a second reservoir for receiving a lipid solution; (d) a dispensing head for introducing lipid solution from the second reservoir into the first reservoir, and (e) a connector joining the second reservoir to the dispensing head for conducting lipid solution from the second reservoir to the dispensing head. The dispensing head has formed therein one or more injection ports having a diameter of 2 mm or less. To use the apparatus, one first prepares a solution of ethanolic lipid comprising from about 1 to about 100 mg/ml lipid in at least 90% by weight ethanol. This ethanolic lipid is injected directly into aqueous buffer through the injection port to make a lipid/buffer mixture, which is mixed by turbulent passage through a static mixer. The resulting lipid vesicles, prior to an extrusion step, are in about 10 % or more by weight ethanol, and have average diameter of from about 80 nm to about 200 nm.
摘要翻译：使用用于制备脂质囊泡的装置实现脂质囊泡的改进的产生，其包括：（a）用于接收缓冲组合物的第一储存器; （b）用于在第一储存器中搅拌缓冲剂组合物的静态混合器; （c）用于接收脂质溶液的第二储存器; （d）用于将脂质溶液从第二储存器引入第一储存器的分配头，以及（e）将第二储存器连接到分配头的连接器，用于将脂溶液从第二储存器传导到分配头。分配头在其中形成有一个或多个直径为2mm或更小的注射口。为了使用该装置，首先首先在至少90重量％的乙醇中制备包含约1至约100mg / ml脂质的乙醇脂质溶液。该乙醇脂质通过注射口直接注入含水缓冲液中以制备脂质/缓冲液混合物，通过静态混合器通过湍流混合。在挤出步骤之前，所得的脂质囊泡的重量在约10％或更多的乙醇中，平均直径为约80nm至约200nm。

4. 发明申请

WO2013185116A1 LIPIDS FOR THERAPEUTIC AGENT DELIVERY FORMULATIONS 审中-公开
标题翻译：用于治疗药物递送配方的药物
公开(公告)号：WO2013185116A1
公开(公告)日：2013-12-12
申请号：PCT/US2013/044849
申请日：2013-06-07
申请人： PAYNE, Joseph, E. , GAUDETTE, John, A. , HOU, Zheng , AHMADIAN, Mohammad , YU, Lei , KNOPOV, Victor , AKOPIAN, Violetta , KARMALI, Priya , WITTE, Richard, P. , SAFARZADEH, Neda , YING, Wenbin , ZHANG, Jun
发明人： PAYNE, Joseph, E. , GAUDETTE, John, A. , HOU, Zheng , AHMADIAN, Mohammad , YU, Lei , KNOPOV, Victor , AKOPIAN, Violetta , KARMALI, Priya , WITTE, Richard, P. , SAFARZADEH, Neda , YING, Wenbin , ZHANG, Jun
IPC分类号： C07C271/16 , C07D333/40 , C07C317/44 , C07C321/14 , C07C333/04 , C07C235/08 , C07C237/08 , C07D207/16 , A61K47/16 , A61K47/18 , A61K47/22
CPC分类号： A61K47/20 , A61K9/1272 , A61K47/14 , A61K47/18 , A61K47/22 , C07C235/08 , C07C237/08 , C07C237/16 , C07C271/16 , C07C317/44 , C07C323/60 , C07C333/04 , C07D207/16 , C07D333/38 , C07D333/40 , Y10T428/2998
摘要： The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.
摘要翻译：该描述针对可用于增强脂质体中治疗剂递送的可离子化脂质。

5. 发明申请

WO2012170957A2 RETINOID-LIPOSOMES FOR ENHANCING MODULATION OF HSP47 EXPRESSION 审中-公开
标题翻译：用于增强HSP47表达调控的反义脂质体
公开(公告)号：WO2012170957A2
公开(公告)日：2012-12-13
申请号：PCT/US2012041761
申请日：2012-06-08
申请人： NITTO DENKO CORP , QUARK PHARMACEUTICALS INC , NNTSU YOSHIRO , PAYNE JOSEPH E , KNOPOV VICTOR , AKOPIAN VIO ETTA , W TTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , FEINSTEIN ELENA , AVK N-NAHUM SHARON , KAL NSKI HAGAR , METT IGOR , MINOMI KENJIRO , Y NG WENBIN , LUI YUN
发明人： NNTSU YOSHIRO , PAYNE JOSEPH E , KNOPOV VICTOR , AKOPIAN VIO ETTA , W TTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , FEINSTEIN ELENA , AVK N-NAHUM SHARON , KAL NSKI HAGAR , METT IGOR , MINOMI KENJIRO , Y NG WENBIN , LUI YUN
IPC分类号： A61K48/00 , A61K38/17
CPC分类号： A61K9/1271 , A61K9/127 , A61K31/713 , C07H21/02 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/14 , C12N2320/32 , C12N2320/52
摘要： What is described are pharmaceutical compositions comprising a double-stranded nucleic acid molecule comprising a sense strand and an antisense strand wherein the sense and antisense strands are selected from the oligonucleotides described as SERPINH1_2 (SEQ ID NOS: 60 and 127), SERPTNHl_45a (SEQ ID NOS: 98 and 165), and SERPTNH1_51 (SEQ ID NOS: 101 and 168), and drug carrier comprising a mixture of a retinoid and a lipid vesicle, and methods of using these pharmaceutical compositions to treat a disease associated with hsp47 espresssion, including fibrosis.
摘要翻译：所描述的是包含包含有义链和反义链的双链核酸分子的药物组合物，其中有义链和反义链选自描述为SERPINH1_2的寡核苷酸（SEQ ID NO：60和127），SERPTNH1_45a（SEQ ID NO： NOS：98和165）和SERPTNH1_51（SEQ ID NO：101和168）和包含类视黄醇和脂质囊泡的混合物的药物载体，以及使用这些药物组合物治疗与hsp47浓缩有关的疾病的方法，包括纤维化。

6. 发明申请

WO2012170952A9 COMPOUNDS FOR TARGETING DRUG DELIVERY AND ENHANCING SIRNA ACTIVITY 审中-公开
公开(公告)号：WO2012170952A9
公开(公告)日：2013-02-21
申请号：PCT/US2012041753
申请日：2012-06-08
申请人： NITTO DENKO CORP , NIITSU YOSHIRO , PAYNE JOSEPH E , HOU ZHENG , GAUDETTE JOHN A , NAGARAJAN SRIDHAR C , KNOPOV VICTOR , WITTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , AKOPIAN VIOLETTA , KARMALI PRIYA
发明人： NIITSU YOSHIRO , PAYNE JOSEPH E , HOU ZHENG , GAUDETTE JOHN A , NAGARAJAN SRIDHAR C , KNOPOV VICTOR , WITTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , AKOPIAN VIOLETTA , KARMALI PRIYA
IPC分类号： C07C237/08 , A61K31/16 , A61P1/16 , C07C237/22 , C07C323/60 , C07C333/04
CPC分类号： C07C237/08 , A61K9/1271 , C07C237/22 , C07C323/60 , C07C333/04
摘要： Here described are compounds of formula I: wherein R1 and R2 is independently selected from a group consisting of C10 to C18 alkyl, C12 to C18 alkenyl, and oleyl group; wherein R3 and R4 are independently selected from a group consisting of C1 to C6 alkyl, and C2 to C6 alkanol; wherein X is selected from a group consisting of -CH2-, -S-, and -O- or absent; wherein Y is selected from -(CH2)n, -S(CH2)n, -O(CH2)n-, thiophene, -SO2(CH2)n-, and ester, wherein n = 1 -4; wherein a = 1 -4; wherein b=l -4; wherein c=l-4; and wherein Z is a counterion; and compounds consisting of the structure (targeting molecule)m-linker-(targeting molecule)n, wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including one or both of these compounds which are useful for the delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.

7. 发明申请

WO2012170957A8 RETINOID-LIPOSOMES FOR ENHANCING MODULATION OF HSP47 EXPRESSION 审中-公开
公开(公告)号：WO2012170957A8
公开(公告)日：2012-12-13
申请号：PCT/US2012/041761
申请日：2012-06-08
申请人： NITTO DENKO CORPORATION , NIITSU, Yoshiro , PAYNE, Joseph E. , KNOPOV, Victor , AKOPIAN, Violetta , WITTE, Richard P. , AHMADIAN, Mohammad , PERELMAN, Loren A. , TANAKA, Yasunobu , FEINSTEIN, Elena , AVKIN-NAHUM, Sharon , KALINSKI, Hagar , METT, Igor , MINOMI, Kenjiro , YING, Wenbin , LIU, Yun
发明人： NIITSU, Yoshiro , PAYNE, Joseph E. , KNOPOV, Victor , AKOPIAN, Violetta , WITTE, Richard P. , AHMADIAN, Mohammad , PERELMAN, Loren A. , TANAKA, Yasunobu , FEINSTEIN, Elena , AVKIN-NAHUM, Sharon , KALINSKI, Hagar , METT, Igor , MINOMI, Kenjiro , YING, Wenbin , LIU, Yun
IPC分类号： C12N15/113 , C12N15/11 , A61K31/713
摘要： What is described are pharmaceutical compositions comprising a double-stranded nucleic acid molecule comprising a sense strand and an antisense strand wherein the sense and antisense strands are selected from the oligonucleotides described as SERPINH1_2 (SEQ ID NOS: 60 and 127), SERPTNHl_45a (SEQ ID NOS: 98 and 165), and SERPTNH1_51 (SEQ ID NOS: 101 and 168), and drug carrier comprising a mixture of a retinoid and a lipid vesicle, and methods of using these pharmaceutical compositions to treat a disease associated with hsp47 espresssion, including fibrosis.

8. 发明申请

WO2012170952A4 COMPOUNDS FOR TARGETING DRUG DELIVERY AND ENHANCING SIRNA ACTIVITY 审中-公开
标题翻译：靶向药物递送和增强SIRNA活性的化合物
公开(公告)号：WO2012170952A4
公开(公告)日：2013-05-30
申请号：PCT/US2012041753
申请日：2012-06-08
申请人： NITTO DENKO CORP , NIITSU YOSHIRO , PAYNE JOSEPH E , HOU ZHENG , GAUDETTE JOHN A , NAGARAJAN SRIDHAR C , KNOPOV VICTOR , WITTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , AKOPIAN VIOLETTA , KARMALI PRIYA
发明人： NIITSU YOSHIRO , PAYNE JOSEPH E , HOU ZHENG , GAUDETTE JOHN A , NAGARAJAN SRIDHAR C , KNOPOV VICTOR , WITTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , AKOPIAN VIOLETTA , KARMALI PRIYA
IPC分类号： C07C237/08 , A61K31/16 , A61P1/16 , C07C237/22 , C07C323/60 , C07C333/04
CPC分类号： C07C237/08 , A61K9/1271 , C07C237/22 , C07C323/60 , C07C333/04
摘要： Here described are compounds of formula I: wherein R1 and R2 is independently selected from a group consisting of C10 to C18 alkyl, C12 to C18 alkenyl, and oleyl group; wherein R3 and R4 are independently selected from a group consisting of C1 to C6 alkyl, and C2 to C6 alkanol; wherein X is selected from a group consisting of -CH2-, -S-, and -O- or absent; wherein Y is selected from -(CH2)n, -S(CH2)n, -O(CH2)n-, thiophene, -SO2(CH2)n-, and ester, wherein n = 1 -4; wherein a = 1 -4; wherein b=l -4; wherein c=l-4; and wherein Z is a counterion; and compounds consisting of the structure (targeting molecule)m-linker-(targeting molecule)n, wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including one or both of these compounds which are useful for the delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.
摘要翻译：这里描述的是式I的化合物：其中R 1和R 2独立地选自由C 10至C 18烷基，C 12至C 18烯基和油烯基组成的组; 其中R3和R4独立地选自C1-C6烷基和C2-C6链烷醇; 其中X选自-CH 2 - ， - S-和-O-或不存在; 其中Y选自 - （CH2）n，-S（CH2）n，-O（CH2）n-，噻吩，-SO2（CH2）n-和酯，其中n = 1-4; 其中a = 1-4; 其中b = 1-4; 其中c = 1-4; 并且其中Z是抗衡离子; 和由结构（靶向分子）m-连接体 - （靶向分子）n组成的化合物，其中靶向分子是在靶细胞上具有特定受体的类视黄醇或脂溶性维生素; 其中m和n独立地为0,1,2或3; 并且其中接头包含聚乙二醇（PEG）或PEG-样分子，以及包含用于递送治疗剂的这些化合物中的一种或两种的组合物和药物制剂; 以及使用这些组合物和药物制剂的方法。

9. 发明申请

WO2012170952A3 COMPOUNDS FOR TARGETING DRUG DELIVERY AND ENHANCING SIRNA ACTIVITY 审中-公开
标题翻译：用于靶向药物递送和增强SIRNA活性的化合物
公开(公告)号：WO2012170952A3
公开(公告)日：2013-04-11
申请号：PCT/US2012041753
申请日：2012-06-08
申请人： NITTO DENKO CORP , NIITSU YOSHIRO , PAYNE JOSEPH E , HOU ZHENG , GAUDETTE JOHN A , NAGARAJAN SRIDHAR C , KNOPOV VICTOR , WITTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , AKOPIAN VIOLETTA , KARMALI PRIYA
发明人： NIITSU YOSHIRO , PAYNE JOSEPH E , HOU ZHENG , GAUDETTE JOHN A , NAGARAJAN SRIDHAR C , KNOPOV VICTOR , WITTE RICHARD P , AHMADIAN MOHAMMAD , PERELMAN LOREN A , TANAKA YASUNOBU , AKOPIAN VIOLETTA , KARMALI PRIYA
IPC分类号： C07C237/08 , A61K31/16 , A61P1/16 , C07C237/22 , C07C323/60 , C07C333/04
CPC分类号： C07C237/08 , A61K9/1271 , C07C237/22 , C07C323/60 , C07C333/04
摘要： Here described are compounds of formula I: wherein R1 and R2 is independently selected from a group consisting of C10 to C18 alkyl, C12 to C18 alkenyl, and oleyl group; wherein R3 and R4 are independently selected from a group consisting of C1 to C6 alkyl, and C2 to C6 alkanol; wherein X is selected from a group consisting of -CH2-, -S-, and -O- or absent; wherein Y is selected from -(CH2)n, -S(CH2)n, -O(CH2)n-, thiophene, -SO2(CH2)n-, and ester, wherein n = 1 -4; wherein a = 1 -4; wherein b=l -4; wherein c=l-4; and wherein Z is a counterion; and compounds consisting of the structure (targeting molecule)m-linker-(targeting molecule)n, wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including one or both of these compounds which are useful for the delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.
摘要翻译：这里描述的是式I化合物：其中R 1和R 2独立地选自C 10至C 18烷基，C 12至C 18烯基和油基; 其中R3和R4独立地选自C1-C6烷基和C2-C6链烷醇; 其中X选自-CH 2 - ， - S-和-O-或不存在; 其中Y选自 - （CH 2）n，-S（CH 2）n，-O（CH 2）n - ，噻吩，-SO 2（CH 2）n - 和酯，其中n = 1-4; 其中a = 1-4; 其中b = 1-4; 其中c = 1-4; 并且其中Z是抗衡离子; 以及由结构（靶向分子）m-接头（靶向分子）n组成的化合物，其中靶向分子是靶细胞上具有特异性受体的类视黄醇或脂溶性维生素; 其中m和n独立地为0,1,2或3; 并且其中所述接头包含聚乙二醇（PEG）或PEG样分子，以及包含这些化合物中的一种或两种可用于递送治疗剂的组合物和药物制剂; 以及使用这些组合物和药物制剂的方法。

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