公开(公告)号：US06627194B1

公开(公告)日：2003-09-30

申请号：US08694315

申请日：1996-08-08

Applicant: Haruo Yoshii ,  Mitsuru Naiki ,  Yuriko Fukata

Inventor： Haruo Yoshii ,  Mitsuru Naiki ,  Yuriko Fukata

IPC: A61K39395

CPC classification number: C07K16/18 ,  A61K38/00 ,  Y10S424/81 ,  Y10S530/868

Abstract: Activated immunoglobulin which is useful as an eosinophilia-suppressing agent, immunomodulating agent, therapeutic agent for autoimmune diseases, anfiinflammatory agent and antiallergic agent is obtained by admixing immunoglobulin with a histamine component and then substantially or completely removing the histamine component. The histamine component may be removed or separated by dialysis, gel filtration, adsorption chromatography, ion exchange chromatography, or affinity chromatography. The method imparts pharmacological activity which is not inherently available in immunoglobulin of the natural type to immunoglobulin. The activated immunoglobulin of the present invention has an immunomodulating action which is clearly different from that of conventional immunosuppressive agents. It is useful as a therapeutic agent for autoimmune diseases such as chronic rheumatoid arthritis, systemic lupus erythematodes and multiple sclerosis as well as for various immunodeficiency syndromes wherein the immune system is not functioning properly. The activated immunoglobulin of the present invention may be also used as a pharmaceutical agent for eosinophilia caused by infectious diseases, parasitic diseases, diseases of respiratory organs, autoimmune diseases, malignant tumors, etc. In addition, the product of the invention may be used as an excellent antiinflammatory agent and antiallergic agent, and so is highly useful as a pharmaceutical.

Abstract translation: 通过将免疫球蛋白与组胺成分混合，然后基本上或完全除去组胺成分，得到可用作嗜酸性粒细胞增多抑制剂，免疫调节剂，自身免疫性疾病治疗剂，抗炎药和抗过敏药物的活性免疫球蛋白。 组胺组分可以通过透析，凝胶过滤，吸附色谱，离子交换层析或亲和层析来去除或分离。 该方法赋予在天然免疫球蛋白免疫球蛋白免疫球蛋白中本身不具有的药理学活性。 本发明的活化免疫球蛋白具有与常规免疫抑制剂明显不同的免疫调节作用。 它可用作自身免疫疾病如慢性类风湿性关节炎，系统性红斑狼疮和多发性硬化以及各种免疫缺陷综合征的治疗剂，其中免疫系统不能正常运作。 本发明的活化免疫球蛋白也可以用作由感染性疾病，寄生虫病，呼吸器官疾病，自身免疫性疾病，恶性肿瘤等引起的嗜酸性粒细胞增多的药剂。此外，本发明的产品可以用作 优异的抗炎剂和抗过敏剂，因此作为药物是非常有用的。

公开(公告)号：US5856113A

公开(公告)日：1999-01-05

申请号：US687778

申请日：1996-07-31

Applicant: Haruo Yoshii ,  Yuriko Fukata

Inventor： Haruo Yoshii ,  Yuriko Fukata

IPC: G01N33/53 ,  G01N33/531 ,  G01N33/535 ,  G01N33/80 ,  G01N33/555

CPC classification number: G01N33/80

Abstract: Fragments of cell membrane of erythrocyte are used as an antigen for insolubilization in enzyme immunoassay to provide a highly sensitive, excellent quantitative method for measuring anti-erythrocyte antibody. The cell membrane fragments of erythrocyte are the residual membrane fraction after removal of soluble cytoplasm proteins which interfere with the absorbance analysis of enzyme-linked immunosorbent assay (ELISA). The cell membrane fragments of erythrocyte which are used as an antigen may be prepared by destroying the erythrocytes to obtain a cell membrane fragment fraction and a cytoplasm protein fraction. The two fractions may be separated or fractionated by gel filtration, ultrafiltration or centrifugation to isolate the cell membrane fragment fraction. A solution of the cell membrane fragments of erythrocyte is substantially transparent and is useful as an insolubilized antigen for ELISA. The antigen is shelf stable for extended periods when stored in a cool, dark location. An antigen which consists of erythrocyte membrane fragments can be prepared by simple operations and, therefore, it is possible to easily obtain large quantities of antigen for insolubilization.

Abstract translation: 红细胞的细胞膜片段用作酶免疫测定中的不溶性抗原，为测定抗红细胞抗体提供了高灵敏度，优异的定量方法。 红细胞的细胞膜片段是去除可溶性细胞质蛋白后的残留膜部分，其干扰酶联免疫吸附测定（ELISA）的吸光度分析。 用作抗原的红细胞的细胞膜片段可以通过破坏红细胞来获得细胞膜片段和细胞质蛋白质级分来制备。 可以通过凝胶过滤，超滤或离心分离或分离两个级分以分离细胞膜片段级分。 红细胞的细胞膜片段的溶液基本上是透明的，可用作ELISA的不溶抗原。 当存放在阴凉，阴凉的地方时，抗原可长时间保持稳定。 由红细胞膜片段组成的抗原可以通过简单的操作制备，因此可以容易地获得大量的用于不溶解的抗原。

公开(公告)号：US5780026A

公开(公告)日：1998-07-14

申请号：US287249

申请日：1994-08-08

Applicant: Haruo Yoshii ,  Yuriko Fukata

Inventor： Haruo Yoshii ,  Yuriko Fukata

IPC: A61K39/395 ,  A61P7/00 ,  A61P29/00 ,  A61P37/00 ,  A61P43/00 ,  A61K35/14 ,  A61K35/16

CPC classification number: A61K39/395 ,  Y10S514/826 ,  Y10S514/885 ,  Y10S514/887

Abstract: In the present invention, pharmaceutical compositions containing a histamine-added gamma-globulin as an effective component are used as an immunomodulating agent, a suppressive agent for eosinophilia, and as an antiinflammatory agent. The immunomodulating action is unexpectedly different from the action of conventional immunosuppressive agents. Accordingly, the compositions are useful as a pharmaceutical agent for the therapy of diseases associated with an abnormal immune system such as chronic articular rheumatism, systemic lupus erythematosus, multiple sclerosis, etc. and various types of immunodeficiency syndromes. In addition, the pharmaceutical compositions exhibit suppressive action upon hypereosinophilicity. They may be used as a therapeutic agent for infectious diseases, parasitic diseases, respiratory diseases, autoimmune diseases and eosinophilia caused by malignant tumors. The compositions are excellent antiinflammatory agents.

公开(公告)号：US06566386B2

公开(公告)日：2003-05-20

申请号：US09840331

申请日：2001-04-23

Applicant: Haruo Yoshii ,  Yuriko Fukata

Inventor： Haruo Yoshii ,  Yuriko Fukata

IPC: A61K31417

CPC classification number: A61K39/395 ,  Y10S424/81 ,  Y10S530/868 ,  A61K2300/00

Abstract: In the present invention, pharmaceutical compositions containing a histamine-added gamma-globulin as an effective component are used as an immunomodulating agent, a suppressive agent for eosinophilia, and as an antiinflammatory agent. The immunomodulating action is unexpectedly different from the action of conventional immunosuppressive agents. Accordingly, the compositions are useful as a pharmaceutical agent for the therapy of diseases associated with an abnormal immune system such as chronic articular rheumatism, systemic lupus erythematosus, multiple sclerosis, etc. and various types of immunodeficiency syndromes. In addition, the pharmaceutical compositions exhibit suppressive action upon hypereosinophilicity. They may be used as a therapeutic agent for infectious diseases, parasitic diseases, respiratory diseases, autoimmune diseases and eosinophilia caused by malignant tumors. The compositions are excellent antiinflammatory agents.

公开(公告)号：US06187803B1

公开(公告)日：2001-02-13

申请号：US09013202

申请日：1998-01-26

Applicant: Haruo Yoshii ,  Yuriko Yamazaki

Inventor： Haruo Yoshii ,  Yuriko Yamazaki

IPC: A61K31415

CPC classification number: C07K16/44 ,  A61K47/6803 ,  A61K2039/505

Abstract: A drug preparation for oral administration containing histamine-added immunoglobulin as an effective component may be used for prevention or treatment of allergic diseases such as bronchial asthma, allergic rhinitis, vasomotor rhinitis, urticaria, chronic eczema and atopic dermatitis; autoimmune diseases such as multiple sclerosis, chronic rheumatoid arthritis and systemic lupus erythematodes; various immunodeficiency syndromes; and also eosinophilia or various inflammatory diseases caused by infectious diseases, parasitic diseases, diseases of respiratory organs, autoimmune diseases, and malignant tumors. The drug preparation which can be administered orally can be taken by patients easier than an injectable preparation without loss of effectiveness. Therefore, the drug preparation for oral administration of the present invention is practical and highly useful.

Abstract translation: 用于含有组胺加免疫球蛋白作为有效成分的口服给药制剂可用于预防或治疗过敏性疾病如支气管哮喘，过敏性鼻炎，血管舒缩性鼻炎，荨麻疹，慢性湿疹和特应性皮炎; 自身免疫性疾病如多发性硬化，慢性类风湿性关节炎和系统性红斑狼疮; 各种免疫缺陷综合征 以及由感染性疾病，寄生虫病，呼吸器官疾病，自身免疫疾病和恶性肿瘤引起的嗜酸粒细胞增多或各种炎性疾病。 可以口服给药的药物制剂可以比注射制剂容易地服用，而不会失去有效性。 因此，本发明的口服给药制剂是实用且非常有用的。

公开(公告)号：US06440978B2

公开(公告)日：2002-08-27

申请号：US09833274

申请日：2001-04-12

Applicant: Haruo Yoshii ,  Akihiro Fujita

Inventor： Haruo Yoshii ,  Akihiro Fujita

IPC: A61K31505

CPC classification number: A61K31/519 ,  Y10S514/858 ,  Y10S514/859 ,  Y10S514/86 ,  Y10S514/861 ,  Y10S514/862 ,  Y10S514/863 ,  Y10S514/864

Abstract: The present invention provides a therapeutic agent for dermatitis, particularly a therapeutic agent for atopic dermatitis, which is very safe and which shows few adverse side-effects in comparison to, for example, steroidal agents. The present invention relates to a therapeutic agent containing a compound represented by the following formula (I) or a pharmaceutically acceptable salt or hydrate thereof as an effective ingredient: wherein R is hydrogen or a halogen. The therapeutic agent for dermatitis according to the present invention effectively and in a dose-dependent manner suppresses antigen-induced swelling in a mouse ear, a recognized animal model for atopic dermatitis, and suppresses the antigen-induced flare-up reaction in mice which occurred with the swelling reaction. In addition, no adverse reaction in the skin are observed.

Abstract translation: 本发明提供了一种用于皮炎的治疗剂，特别是特应性皮炎的治疗剂，其是非常安全的，并且与例如类固醇剂相比显示出很少的不利副作用。 本发明涉及含有由下式（I）表示的化合物或其药学上可接受的盐或水合物作为有效成分的治疗剂：其中R是氢或卤素。 根据本发明的有效和剂量依赖性的皮炎治疗剂抑制小鼠耳中抗原诱导的肿胀，这是认知的特应性皮炎的动物模型，并且抑制了发生的小鼠中的抗原诱发的起反应 伴随肿胀反应。 此外，没有观察到皮肤的不良反应。