公开(公告)号：EP0477050A2

公开(公告)日：1992-03-25

申请号：EP91402275.1

申请日：1991-08-20

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma, Gen-Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno, Den'Ichi ,  Oshima, Haruyuki Tategaoka-Danchi 2-10-513

IPC分类号： C12N1/20 ,  C12P19/04 ,  A61K31/735

CPC分类号： C12R1/425 ,  A61K35/74 ,  A61K45/05 ,  C12P19/04 ,  C12R1/01 ,  Y02A50/475 ,  Y10S514/885

摘要： Novel LPS having the following physical properties, novel bacilli providing those LPS, and novel immunity stimulators, analgesics, and antiwithdrawal agents, and novel veterinary immunity stimulators, analgesics, and antiwithdrawal agents containing LPS selected from the group consisting of those LPSs and mixtures thereof.
LPS1

Dominant molecular weight: 5,000 ± 1,000 as determined by SDS-PAGE method
Phosphorus number: 2 ± 1 / 5,000 (m.w.)
Hexosamine number: 9 ± 1 / 5,000 (m.w.)
KDO number: 2 ± 1 / 5,000 (m.w.)

LPS2

Dominant molecular weight: 6,500 ± 2,500 as determined by SDS-PAGE method
Phosphorus number: 1 to 2 / 5,000 (m.w.)
Hexosamine number: 7 ± 1 / 5,000 (m.w.)
KDO number: 1 to 2 / 5,000 (m.w.)

LPS3

Dominant molecular weight: 6,500 ± 2,500 as determined by SDS-PAGE method
Phosphorus number: 2 ± 1 / 5,000 (m.w.)
Hexosamine number: 5 ± 1 / 5,000 (m.w.)
KDO number: 2 ± 1 / 5,000 (m.w.)

公开(公告)号：EP0472467A3

公开(公告)日：1993-03-17

申请号：EP91402276.9

申请日：1991-08-20

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma, Gen-Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno, Den'Ichi ,  Oshima, Haruyuki Tategaoka-Danchi 2-10-513

IPC分类号： A61K37/20

CPC分类号： C12R1/425 ,  A61K35/74 ,  A61K45/05 ,  C12P19/04 ,  C12R1/01 ,  Y02A50/475 ,  Y10S514/885

摘要： An analgesic composition comprising an effective amount of at least one member of LPS whose macrophage activation ED₅₀ is 0.4 - 100 ng/ml of culture solution in terms of its limulus test-positive LPS content observed on a sigmoid curve prepared by determining the ability of the LPS to activate the TNF productivity of macrophage cultured in vitro , and plotting the macrophage activation ability (%) along the axis of ordinate wherein the ability is estimated to be 0 % in the case where it corresponds to the quantity of TNF produced by macrophage with no LPS added thereto, and 100 % is assigned to the macrophage activation ability which provides the maximal and constant quantity of TNF produced by the macrophage and plotting the limulus test-positive LPS content of the LPS along the axis of abscissa on a logarithmic scale, in admixture with a pharmaceutically or veterinarily acceptable carrier, such that when administered to an animal, high cholesterol level of said animal is prevented or cured; and
   a method of treating pain of an animal comprising administration to said animal an amount of the above composition effective to prevent or cure the pain of said animal.

公开(公告)号：EP0477050A3

公开(公告)日：1993-03-17

申请号：EP91402275.1

申请日：1991-08-20

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma, Gen-Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno, Den'Ichi ,  Oshima, Haruyuki Tategaoka-Danchi 2-10-513

IPC分类号： C12N1/20 ,  C12P19/04 ,  A61K31/735

CPC分类号： C12R1/425 ,  A61K35/74 ,  A61K45/05 ,  C12P19/04 ,  C12R1/01 ,  Y02A50/475 ,  Y10S514/885

摘要： Novel LPS having the following physical properties, novel bacilli providing those LPS, and novel immunity stimulators, analgesics, and antiwithdrawal agents, and novel veterinary immunity stimulators, analgesics, and antiwithdrawal agents containing LPS selected from the group consisting of those LPSs and mixtures thereof.
LPS1
Dominant molecular weight: 5,000 ± 1,000 as determined by SDS-PAGE method Phosphorus number: 2 ± 1 / 5,000 (m.w.) Hexosamine number: 9 ± 1 / 5,000 (m.w.) KDO number: 2 ± 1 / 5,000 (m.w.)
LPS2
Dominant molecular weight: 6,500 ± 2,500 as determined by SDS-PAGE method Phosphorus number: 1 to 2 / 5,000 (m.w.) Hexosamine number: 7 ± 1 / 5,000 (m.w.) KDO number: 1 to 2 / 5,000 (m.w.)
LPS3
Dominant molecular weight: 6,500 ± 2,500 as determined by SDS-PAGE method Phosphorus number: 2 ± 1 / 5,000 (m.w.) Hexosamine number: 5 ± 1 / 5,000 (m.w.) KDO number: 2 ± 1 / 5,000 (m.w.)

公开(公告)号：EP0472467A2

公开(公告)日：1992-02-26

申请号：EP91402276.9

申请日：1991-08-20

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma, Gen-Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno, Den'Ichi ,  Oshima, Haruyuki Tategaoka-Danchi 2-10-513

IPC分类号： A61K37/20

CPC分类号： C12R1/425 ,  A61K35/74 ,  A61K45/05 ,  C12P19/04 ,  C12R1/01 ,  Y02A50/475 ,  Y10S514/885

摘要： An analgesic composition comprising an effective amount of at least one member of LPS whose macrophage activation ED₅₀ is 0.4 - 100 ng/ml of culture solution in terms of its limulus test-positive LPS content observed on a sigmoid curve prepared by determining the ability of the LPS to activate the TNF productivity of macrophage cultured in vitro , and plotting the macrophage activation ability (%) along the axis of ordinate wherein the ability is estimated to be 0 % in the case where it corresponds to the quantity of TNF produced by macrophage with no LPS added thereto, and 100 % is assigned to the macrophage activation ability which provides the maximal and constant quantity of TNF produced by the macrophage and plotting the limulus test-positive LPS content of the LPS along the axis of abscissa on a logarithmic scale, in admixture with a pharmaceutically or veterinarily acceptable carrier, such that when administered to an animal, high cholesterol level of said animal is prevented or cured; and
   a method of treating pain of an animal comprising administration to said animal an amount of the above composition effective to prevent or cure the pain of said animal.

摘要翻译： 一种镇痛组合物，其包含有效量的至少一种LPS成员，其巨噬细胞活化ED 50为0.4-100ng / ml培养液，其鲎试验阳性LPS含量在通过测定 LPS激活体外培养的巨噬细胞的TNF产生，并绘制沿纵坐标轴的巨噬细胞活化能力（％），其中在与巨噬细胞产生的TNF的量相对应的情况下，该能力估计为0％ 没有添加LPS，并且赋予巨噬细胞活化能力100％，其提供由巨噬细胞产生的TNF的最大和恒定量，并沿着横坐标绘制LPS的鲎试验阳性LPS含量以对数标度绘制， 与药学或兽医学上可接受的载体混合，使得当施用于动物时，防止所述动物的高胆固醇水平或 治愈; 以及治疗动物疼痛的方法，包括向所述动物施用一定量的上述组合物，其有效预防或治愈所述动物的绒毛。

公开(公告)号：EP0462021A2

公开(公告)日：1991-12-18

申请号：EP91401622.5

申请日：1991-06-17

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma, Gen'Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno, Den'Ichi ,  Oshima, Haruyuki

IPC分类号： A61K37/20 ,  A61K35/78 ,  A61K35/74

CPC分类号： A61K36/02 ,  A61K36/06 ,  A61K36/07 ,  A61K36/899 ,  A61K2300/00

摘要： A cholesterol-lowering composition comprising an effective amount of at least one member of LPS whose macrophage activation ED₅₀ is 0.4 - 100 ng/ml of culture solution in terms of its limulus test-positive LPS content observed on a sigmoid curve prepared by determining the ability of the LPS to activate the TNF productivity of macrophage cultured in vitro , and plotting the macrophage activation ability (%) along the axis of ordinate wherein the ability is estimated to be 0 % in the case where it corresponds to the quantity of TNF produced by macrophage with no LPS added thereto, and 100 % is assigned to the macrophage activation ability which provides the maximal and constant quantity of TNF produced by the macrophage and plotting the limulus test-positive LPS content of the LPS along the axis of abscissa on a logarithmic scale, in admixture with a pharmaceutically or veterinarily acceptable carrier, such that when administered to an animal, high cholesterol level of said animal is prevented or cured; and
   a method of treating high cholesterol level of an animal comprising administration to said animal an amount of the above composition effective to prevent or cure the high cholesterol level of said animal.

摘要翻译： 一种胆固醇降低组合物，其包含有效量的至少一种LPS成分，其巨噬细胞活化ED 50为0.4-100ng / ml培养液，其鲎试验阳性LPS含量在通过测定能力制备的乙状曲线上观察到 的LPS以激活体外培养的巨噬细胞的TNF生产力，并绘制沿纵坐标轴的巨噬细胞活化能力（％），其中在对应于由TNFα产生的TNF的量的情况下，该能力估计为0％ 没有添加LPS的巨噬细胞，100％被赋予巨噬细胞活化能力，其提供由巨噬细胞产生的TNF的最大和恒定量，并沿着横坐标绘制LPS的鲎试验阳性LPS含量为对数 与药学或兽医学上可接受的载体混合，使得当施用于动物时，所述动物的高胆固醇水平是预先 通风或治愈; 以及治疗动物的高胆固醇水平的方法，包括向所述动物施用一定量的上述有效预防或治愈所述动物的高胆固醇水平的组合物。

公开(公告)号：EP0477050B1

公开(公告)日：1997-05-21

申请号：EP91402275.1

申请日：1991-08-20

申请人： Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma, Gen-Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno, Den'Ichi ,  Oshima, Haruyuki Tategaoka-Danchi 2-10-513

IPC分类号： C12N1/20 ,  C12P19/04 ,  A61K31/735

CPC分类号： C12R1/425 ,  A61K35/74 ,  A61K45/05 ,  C12P19/04 ,  C12R1/01 ,  Y02A50/475 ,  Y10S514/885

摘要： An analgesic composition comprising an effective amount of at least one member of LPS whose macrophage activation ED50 is 0.4 - 100 ng/ml of culture solution in terms of its limulus test-positive LPS content observed on a sigmoid curve prepared by determining the ability of the LPS to activate the TNF productivity of macrophage cultured in vitro, and plotting the macrophage activation ability (%) along the axis of ordinate wherein the ability is estimated to be 0 % in the case where it corresponds to the quantity of TNF produced by macrophage with no LPS added thereto, and 100 % is assigned to the macrophage activation ability which provides the maximal and constant quantity of TNF produced by the macrophage and plotting the limulus test-positive LPS content of the LPS along the axis of abscissa on a logarithmic scale, in admixture with a pharmaceutically or veterinarily acceptable carrier, such that when administered to an animal, high cholesterol level of said animal is prevented or cured; and a method of treating pain of an animal comprising administration to said animal an amount of the above composition effective to prevent or cure the lain of said animal.

公开(公告)号：EP0533517A1

公开(公告)日：1993-03-24

申请号：EP92402319.5

申请日：1992-08-20

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Tsukioka, Daisuke ,  Yoshimura, Kiyoshi ,  Oshima, Haruyuki ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

IPC分类号： A61K31/715 ,  C12P19/04

CPC分类号： C12P19/04 ,  A61K31/715 ,  Y10S435/822 ,  Y10S514/885

摘要： Novel antiwithdrawal agents and veterinary antiwithdrawal agents are disclosed which contain LPS representative of which having the following physical properties:
LPS1

Dominant molecular weight: 5,000 ± 1,000 as determined by SDS-PAGE method
Phosphorus number: 2 ± 1 / 5,O00 (m-w.)
Hexosamine number: 9 ± 1 / 5,000 (m.w.)
KDO number: 2 ± 1 / 5,000 (m.w.)

LPS2

Dominant molecular weight: 6,500: ± 2,500 as determined by SDS-PAGE method
Phosphorus number: 1 to 2 / 5,000 (m.w.)
Hexosamine number: 7 ± 1 / 5,000 (m.w.)
KDO number: 1 to 2 / 5,000 (m.w.)

LPS3

Dominant molecular weight: 6,500 ± 2,500 as determined by SDS-PAGE method
Phosphorus number: 2 ± 1 / 5,000 (m.w.)
Hexosamine number: 5 ± 1 / 5,000 (m.w.)
KDO number: 2 ± 1 / 5,000 (m.w.)

摘要翻译： 公开了含有代表具有以下物理性质的LPS的新型抗抽出剂和兽用抗抽穗剂：LPS1主要分子量：5,000 +/- 1,000，通过SDS-PAGE法测定磷数：2 +/- 1 / 5,000 （mw。）己糖胺数：9 +/- 1 / 5,000（mw）KDO数：2 +/- 1 / 5,000（mw）LPS2主要分子量：6,500：+/- 2,500，通过SDS-PAGE法测定磷数 ：1〜2 / 5,000（mw）己糖胺数：7 +/- 1 / 5,000（mw）KDO数：1〜2 / 5,000（mw）LPS3主要分子量：6,500 +/- 2,500，通过SDS-PAGE法测定 磷数：2 +/- 1 / 5,000（mw）己糖胺数：5 +/- 1 / 5,000（mw）KDO数：2 +/- 1 / 5,000（mw）e

公开(公告)号：EP0462020A2

公开(公告)日：1991-12-18

申请号：EP91401621.7

申请日：1991-06-17

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma,Gen'Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno Den'Ichi ,  Oshima ,Haruyuki

IPC分类号： A61K37/20 ,  A61K35/78 ,  A61K35/74

CPC分类号： A61K36/02 ,  A61K36/06 ,  A61K36/07 ,  A61K36/899 ,  Y02A50/473 ,  A61K2300/00

摘要： An anti-herpes composition comprising an effective amount of at l east one member of LPS whose macrophage activation ED₅₀ is 0.4 - 100 ng/ml of culture solution in terms of its limulus test-positive LPS content observed on a sigmoid curve prepared by determining the ability of the LPS to activate the TNF productivity of macrophage cultured in vitro , and plotting the macrophage activation ability (%) along the axis of ordinate wherein the ability is estimated to be 0 % in the case where it corresponds to the quantity of TNF produced by macrophage with no LPS added thereto, and 100 % is assigned to the macrophage activation ability which provides the maximal and constant quantity of TNF produced by the macrophage and plotting the limulus test-positive LPS content of the LPS along the axis of abscissa on a logarithmic scale, in admixture with a pharmaceutically or veterinarily acceptable carrier, such that when administered to an animal, herpes of said animal is cured; and
   a method of treating herpes of an animal comprising administration to said animal an amount of the above composition effective to cure the herpes of said animal.

摘要翻译： 一种抗疱疹组合物，其包含有效量的至少一种LPS的成员，其巨噬细胞活化ED 50为0.4-100ng / ml培养液，其鲎试验阳性LPS含量在通过测定能力制备的乙状曲线上观察到 的LPS以激活体外培养的巨噬细胞的TNF生产力，并绘制沿纵坐标轴的巨噬细胞活化能力（％），其中在对应于由TNFα产生的TNF的量的情况下，该能力估计为0％ 没有添加LPS的巨噬细胞，100％被赋予巨噬细胞活化能力，其提供由巨噬细胞产生的TNF的最大和恒定量，并且沿着横坐标绘制LPS的鲎试验阳性LPS含量为对数 与药学或兽医学上可接受的载体混合，使得当施用于动物时，所述动物的疱疹被固化; 以及治疗动物疱疹的方法，包括向所述动物施用一定量的上述有效治愈所述动物疱疹的组合物。

公开(公告)号：EP0462021A3

公开(公告)日：1992-04-29

申请号：EP91401622.5

申请日：1991-06-17

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma, Gen'Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno, Den'Ichi ,  Oshima, Haruyuki

IPC分类号： A61K37/20 ,  A61K35/78 ,  A61K35/74

CPC分类号： A61K36/02 ,  A61K36/06 ,  A61K36/07 ,  A61K36/899 ,  A61K2300/00

摘要： A cholesterol-lowering composition comprising an effective amount of at least one member of LPS whose macrophage activation ED₅₀ is 0.4 - 100 ng/ml of culture solution in terms of its limulus test-positive LPS content observed on a sigmoid curve prepared by determining the ability of the LPS to activate the TNF productivity of macrophage cultured in vitro , and plotting the macrophage activation ability (%) along the axis of ordinate wherein the ability is estimated to be 0 % in the case where it corresponds to the quantity of TNF produced by macrophage with no LPS added thereto, and 100 % is assigned to the macrophage activation ability which provides the maximal and constant quantity of TNF produced by the macrophage and plotting the limulus test-positive LPS content of the LPS along the axis of abscissa on a logarithmic scale, in admixture with a pharmaceutically or veterinarily acceptable carrier, such that when administered to an animal, high cholesterol level of said animal is prevented or cured; and
   a method of treating high cholesterol level of an animal comprising administration to said animal an amount of the above composition effective to prevent or cure the high cholesterol level of said animal.

公开(公告)号：EP0462020A3

公开(公告)日：1992-04-29

申请号：EP91401621.7

申请日：1991-06-17

申请人： CHIBA FLOUR MILLING CO. LTD. ,  Soma, Gen-Ichiro ,  Mizuno, Den'Ichi

发明人： Soma,Gen'Ichiro ,  Yoshimura, Kiyoshi ,  Tsukioka, Daisuke ,  Mizuno Den'Ichi ,  Oshima ,Haruyuki

IPC分类号： A61K37/20 ,  A61K35/78 ,  A61K35/74

CPC分类号： A61K36/02 ,  A61K36/06 ,  A61K36/07 ,  A61K36/899 ,  Y02A50/473 ,  A61K2300/00

摘要： An anti-herpes composition comprising an effective amount of at l east one member of LPS whose macrophage activation ED₅₀ is 0.4 - 100 ng/ml of culture solution in terms of its limulus test-positive LPS content observed on a sigmoid curve prepared by determining the ability of the LPS to activate the TNF productivity of macrophage cultured in vitro , and plotting the macrophage activation ability (%) along the axis of ordinate wherein the ability is estimated to be 0 % in the case where it corresponds to the quantity of TNF produced by macrophage with no LPS added thereto, and 100 % is assigned to the macrophage activation ability which provides the maximal and constant quantity of TNF produced by the macrophage and plotting the limulus test-positive LPS content of the LPS along the axis of abscissa on a logarithmic scale, in admixture with a pharmaceutically or veterinarily acceptable carrier, such that when administered to an animal, herpes of said animal is cured; and
   a method of treating herpes of an animal comprising administration to said animal an amount of the above composition effective to cure the herpes of said animal.