公开(公告)号：US4724210A

公开(公告)日：1988-02-09

申请号：US764128

申请日：1985-08-09

Applicant: Tetsuya Oka ,  Kunio Ohkuma ,  Tetsuo Kawahara ,  Mitsuo Sakoh

Inventor： Tetsuya Oka ,  Kunio Ohkuma ,  Tetsuo Kawahara ,  Mitsuo Sakoh

IPC: C12N15/09 ,  A61K39/145 ,  C12N7/00 ,  C12N7/02 ,  C12R1/91 ,  A61K39/12

CPC classification number: C12N7/00 ,  A61K39/12 ,  A61K39/145 ,  C12N2760/16134 ,  C12N2760/16151

Abstract: Disclosed is a method for the purification of an influenza virus, which comprises subjecting a solution containing the influenza virus to column chromatography using, as a gel for chromatography, a sulfuric acid ester of cellulose or a crosslinked polysaccharide. The method can provide highly purified influenza virus which is useful for obtaining an effective vaccine against influenza.

Abstract translation: 公开了一种用于纯化流感病毒的方法，其包括使用含有流感病毒的溶液进行柱色谱，使用色谱凝胶作为纤维素或交联多糖的硫酸酯。 该方法可以提供高度纯化的流感病毒，其可用于获得针对流感的有效疫苗。

公开(公告)号：US20100183672A1

公开(公告)日：2010-07-22

申请号：US12376625

申请日：2007-08-06

Applicant: Tomomi Kanehara ,  Hiroyuki Yokote ,  Kunio Ohkuma ,  Masahiko Kuranaga ,  Shigeru Morikawa

Inventor： Tomomi Kanehara ,  Hiroyuki Yokote ,  Kunio Ohkuma ,  Masahiko Kuranaga ,  Shigeru Morikawa

IPC: A61K39/285 ,  A61P31/20

CPC classification number: A61K39/275 ,  A61K39/12 ,  A61K2039/5254 ,  C12N2710/24134

Abstract: A safer live smallpox vaccine, which contains a lowered content of revertants, is provided. A process for manufacturing a live smallpox vaccine which comprises steps of: inoculating a master seed solution of an attenuated vaccinia virus to an appropriate number of containers (1 to n wherein n is an integer) of rabbit kidney cells and incubating them; inoculating a portion of the cultured solution obtained from each container to RK-13 cells and to Vero E6 cells and incubating them to thereby select containers which contain a cultured solution that forms plaques in RK-13 cells but not in Vero E6 cells; and preparing a drug substance of vaccine using the aforementioned cultured solution (working seed solution), and a live smallpox vaccine prepared in the aforementioned process.

Abstract translation: 提供了一种更安全的活的天花疫苗，其中含有较低含量的反转体。 一种活天花疫苗的制造方法，包括以下步骤：将减毒痘苗病毒的母种子溶液接种到适合数量的兔肾细胞的容器（1至n，其中n为整数）并孵育; 将从每个容器获得的培养溶液的一部分接种到RK-13​​细胞和Vero E6细胞并孵育，从而选择含有在RK-13​​细胞中形成斑块但不在Vero E6细胞中的培养溶液的容器; 并使用上述培养液（工作种子溶液）制备疫苗的药物物质，以及在上述方法中制备的活天花疫苗。

公开(公告)号：US08030020B2

公开(公告)日：2011-10-04

申请号：US12376625

申请日：2007-08-06

Applicant: Tomomi Kanehara ,  Hiroyuki Yokote ,  Kunio Ohkuma ,  Masahiko Kuranaga ,  Shigeru Morikawa

Inventor： Tomomi Kanehara ,  Hiroyuki Yokote ,  Kunio Ohkuma ,  Masahiko Kuranaga ,  Shigeru Morikawa

IPC: C12P1/00 ,  C12N5/00

CPC classification number: A61K39/275 ,  A61K39/12 ,  A61K2039/5254 ,  C12N2710/24134

Abstract: A safer live smallpox vaccine, which contains a lowered content of revertants, is provided. A process for manufacturing a live smallpox vaccine which comprises steps of: inoculating a master seed solution of an attenuated vaccinia virus to an appropriate number of containers (1 to n wherein n is an integer) of rabbit kidney cells and incubating them; inoculating a portion of the cultured solution obtained from each container to RK-13 cells and to Vero E6 cells and incubating them to thereby select containers which contain a cultured solution that forms plaques in RK-13 cells but not in Vero E6 cells; and preparing a drug substance of vaccine using the aforementioned cultured solution (working seed solution), and a live smallpox vaccine prepared in the aforementioned process.

Abstract translation: 提供了一种更安全的活的天花疫苗，其中含有较低含量的反转体。 一种活天花疫苗的制造方法，包括以下步骤：将减毒痘苗病毒的母种子溶液接种到适合数量的兔肾细胞的容器（1至n，其中n为整数）并孵育; 将从每个容器获得的培养溶液的一部分接种到RK-13​​细胞和Vero E6细胞并孵育，从而选择含有在RK-13​​细胞中形成斑块但不在Vero E6细胞中的培养溶液的容器; 并使用上述培养液（工作种子溶液）制备疫苗的药物物质，以及在上述方法中制备的活天花疫苗。

公开(公告)号：US5292506A

公开(公告)日：1994-03-08

申请号：US783148

申请日：1991-10-28

Applicant: Masaharu Oki ,  Hideya Tsuge ,  Kunio Ohkuma ,  Tetsuya Oka

Inventor： Masaharu Oki ,  Hideya Tsuge ,  Kunio Ohkuma ,  Tetsuya Oka

IPC: A61K38/00 ,  A61K38/14 ,  A61K39/00 ,  A61K39/145 ,  C07K9/00 ,  A61K39/12 ,  A61K37/00 ,  A61K37/10

CPC classification number: A61K39/145 ,  A61K39/12 ,  A61K39/39 ,  C07K9/005 ,  A61K2039/5555 ,  A61K38/00 ,  A61K39/00 ,  C12N2760/16134 ,  Y10S424/812

Abstract: Novel muramyldipeptide derivatives such as [6-0-(2-tetradecylhexadecanoyl)-N-acetylmuramoyl]-L-alanyl-D-glutamamide and [6-0-(2-tetradecylhexadecanoyl)-N-acetylmuramoyl]-L-alanyl-N -methyl-D-glutamamide are provided. The muramyldipeptide derivatives are excellent compound as an adjuvant or a constituting component of virosome vaccine. An influenza vaccine comprises a complex of the muramyldipeptide derivative and an influenza virus antigen. The influenza vaccine has excellent antibody-producing capacity and safety.

Abstract translation: 新的胞壁酰二肽衍生物如（6-0-（2-十四烷基十六烷酰基）-N-乙酰基氨基甲酰基）-L-丙氨酰-D-谷氨酰胺和（6-0-（2-十四烷基十六烷酰基）-N-乙酰基甲酰基）-L-丙氨酰-N 甲基-D-谷氨酰胺。 胞壁酰二肽衍生物是作为病毒颗粒疫苗的佐剂或构成成分的优异化合物。 流感疫苗包含胞壁酰二肽衍生物和流感病毒抗原的复合物。 流感疫苗具有优异的抗体生产能力和安全性。

公开(公告)号：US4725547A

公开(公告)日：1988-02-16

申请号：US764132

申请日：1985-08-09

Applicant: Kuniaki Sakamoto ,  Kunio Ohkuma ,  Tetsuo Kawahara ,  Mitsuo Sakoh

Inventor： Kuniaki Sakamoto ,  Kunio Ohkuma ,  Tetsuo Kawahara ,  Mitsuo Sakoh

IPC: C12N15/09 ,  A61K39/205 ,  C12N7/00 ,  C12N7/02 ,  C12R1/91 ,  A61K39/12

CPC classification number: C12N7/00 ,  A61K39/12 ,  A61K39/205 ,  A61K2039/5252 ,  C12N2760/20134 ,  C12N2760/20151

Abstract: Disclosed is a method for the purification of rabic virus, which comprises subjecting a solution containing the rabic virus to column chromatography using, as a gel for chromatography, a sulfuric acid ester of cellulose or a crosslinked polysaccharide. The method can provide highly purified rabic virus which is useful for obtaining an effective vaccine against rabies.

Abstract translation: 公开了一种用于纯化狂犬病毒的方法，其包括使用含有所述狂犬病病毒的溶液进行柱色谱，使用色谱法作为凝胶进行纤维素或交联多糖的硫酸酯。 该方法可以提供高度纯化的狂犬病病毒，其可用于获得针对狂犬病的有效疫苗。

公开(公告)号：US4826687A

公开(公告)日：1989-05-02

申请号：US867539

申请日：1986-05-28

Applicant: Kuniaki Nerome ,  Akira Oya ,  Kunio Ohkuma ,  Atsuo Inoue

Inventor： Kuniaki Nerome ,  Akira Oya ,  Kunio Ohkuma ,  Atsuo Inoue

IPC: A61K39/102 ,  A61K9/127 ,  A61K9/50 ,  A61K39/145 ,  A61K39/39 ,  A61P31/12 ,  A61P31/16 ,  A61K39/22 ,  A61K39/12 ,  B01J13/02

CPC classification number: A61K39/145 ,  A61K39/12 ,  A61K9/1271 ,  A61K9/1272 ,  A61K9/1277 ,  A61K9/5068 ,  A61K2039/5555 ,  A61K2039/55555 ,  C12N2760/16134 ,  Y10S436/829 ,  Y10S514/885 ,  Y10T428/2984

Abstract: This invention relates to a novel influenza vaccine comprising a complex of HANA antigen and an MDP derivative.The novel vaccine is prepared by mixing an influenza HANA antigen and at least one MDP derivative in a suitable medium; solubilizing the resulting mixture with a surface active agent capable of being removed by dialysis, the solubilization being conducted in the presence or absence of cholesterol, lecithin and dicetyl phosphate or a mixture thereof; and then removing the surface active agent therefrom by dialysis to obtain an influenza vaccine comprising artificial vesicle-like particles of a complex of HANA antigen and MDP derivative, where the MDP derivative forms a membrane of the particle (corresponding to the lipid membrane of natural influenza virus particle) on the surface of which there exists the HANA antigen being bonded to the MDP derivative so as to form the complex. Thus, said artificial vesicle-like particle of the HANA antigen-MDP derivative complex has nearly the same particle size and shape as the natural influenza virus particle.The novel vaccine has an improved immunogenicity compared with the conventional vaccine.

Abstract translation: 本发明涉及包含HANA抗原和MDP衍生物的复合物的新型流感疫苗。 通过将流感HANA抗原和至少一种MDP衍生物混合在合适的培养基中来制备新型疫苗; 将所得混合物与能够通过透析除去的表面活性剂溶解，所述溶解在胆固醇，卵磷脂和磷酸二鲸蜡酯或其混合物存在或不存在下进行; 然后通过透析除去表面活性剂，得到包含HANA抗原和MDP衍生物的复合物的人造囊泡状颗粒的流感疫苗，其中MDP衍生物形成颗粒膜（对应于天然流感的脂质膜 病毒颗粒），其表面上存在与MDP衍生物键合的HANA抗原，以形成复合物。 因此，HANA抗原-MDP衍生物复合物的所述人造囊泡状颗粒具有与天然流感病毒颗粒几乎相同的粒度和形状。 与常规疫苗相比，新型疫苗具有改善的免疫原性。