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RED BLOOD CELL PROTECTIVE AGENT

Foreign code F180009547
File No. S2017-0336-C0
Posted date Nov 2, 2018
Country WIPO
International application number 2018JP005391
International publication number WO 2018151243
Date of international filing Feb 16, 2018
Date of international publication Aug 23, 2018
Priority data
  • P2017-028738 (Feb 20, 2017) JP
Title RED BLOOD CELL PROTECTIVE AGENT
Abstract Provided is a red blood cell protective agent that allows for longer-term storage and safer use of a red blood cell-containing solution (e.g., red blood cell concentrate). When red blood cells are stored for a long period of time, phosphatidylserine (PS) is expressed on the surface of the red blood cell membranes. This red blood cell protective agent contains a histidine-rich glycoprotein (HRG) as an active component. HRG suppresses PS expression on red blood cell surfaces, and allows for longer-term storage and safer use of a red blood cell-containing solution.
Outline of related art and contending technology BACKGROUND ART
A blood product transfusion preparation red blood cells, plasma product, formulation and the whole blood platelet product and the like. Formulations are red blood cells, blood plasma, blood cells and platelets and remove the majority of the present invention. (Red blood cell: RBC) is the red blood cells, red blood cells and stored for a long time break down a dielectric film, release of hemoglobin, so-called hemolysis occurs. Is the blood concentrate, acid-sodium citrate-dextrose (Acid-citrate-dextrose) ACD solution including citric acid sodium-sodium phosphate-dextrose (Citrate-phosphate-dextrose) including CPD solution has been used more in the past. Further de-to compensate for the loss by reaction with the adenine, in recent years are adenine is added to the storage solution. 2-3 ° C. is the storage temperature after the valid period is 3 weeks and the blood, can be extended for up to 6 conditions is called. Continuously refrigerated storage of red blood cells however, a reduction in the consumption of glucose, metabolic wastes (i.e., lactic acid and a hydrogen ion) was confirmed to increase. Such a reduction in the metabolism of glucose, adenosine triphosphate (ATP) is depleted, causing a degradation of the red blood cells. After separating the cells from whole blood, red blood cells have been developed for storing. For example, (trade name) (AS-1) Adsol, (trade name) (AS-3) Nutricel, (trade name) (AS-5) Optosol Erythro-sol (trade name) and the like. These AS (AS-1, and the AS-3 AS-2) is, saline, adenine, glucose, as well as the 'protective agent of the cell membrane' a small amount of citric acid and/or as in the mannitol. Adenine and dextrose, at least one of the protective film 1 in an amount of sugar, blood pH buffer system for storage of the compositions and methods disclosed (Patent Document 1) is for.
Glycoprotein apoAII (Histidine-rich glycoprotein; HRG) is, in the year 1972 to about 80kDa molecular weight identified by Heimburger et al (1972) plasma protein. A total of 507 amino acids, wherein the histidine containing protein histidine and 66 high there, primarily synthesized in the liver, about 100-150μg/ml human is considered very high concentration present in the plasma. HRG is, the adjustment of the fibrinolytic system and coagulation line involved in the regulation of angiogenesis has been known (Non-Patent Document 1). Further, by administering the polypeptide HRG method of inhibiting angiogenesis, HRG polypeptide, a polypeptide an antibody that binds to the receptor and HRG, HRG-deficient plasma and polynucleotides, HRG vector encoding the polypeptide and host cells, the product and the pharmaceutical composition has been disclosed (Patent Document 2). In addition, relates to the field of angiogenesis, including HRG from the subfragments of the central region of the anti-angiogenic activity of the polypeptide is substantially pure of the continuous (Patent Document 3) there is a disclosure relating to the use. Further, the active ingredients of the neutrophils HRG-vascular endothelial cell adhesion inhibitor (Patent Document 4) is also described.
However, the safety of the red blood cells by HRG, the effect of stability will be, has not been reported. To protect the red blood cells has been desired the development of additional methods.
Scope of claims (In Japanese)請求の範囲
[請求項1]
ヒスチジンリッチ糖タンパク質を有効成分として含有する、赤血球保護剤。
[請求項2]
赤血球の保護が、ヒスチジンリッチ糖タンパク質により赤血球膜表面のホスファチジルセリンの発現を抑制することによる、請求項1に記載の赤血球保護剤。
[請求項3]
赤血球の保護が、赤血球細胞内のカルシウムイオン濃度を低下することによる、請求項1に記載の赤血球保護剤。
[請求項4]
赤血球の保護が、赤血球細胞内の抗酸化酵素の遊離を抑制することによる、請求項1に記載の赤血球保護剤。
[請求項5]
ヒスチジンリッチ糖タンパク質を有効成分として含有する、赤血球含有溶液の安定化剤。
[請求項6]
請求項1~4のいずれかに記載の赤血球保護剤を含む、赤血球含有溶液の安定化剤。
[請求項7]
請求項5又は6に記載の安定化剤を赤血球含有溶液に添加することを特徴とする、赤血球含有溶液の安定化方法。
[請求項8]
ヒスチジンリッチ糖タンパク質を有効成分として含有する、赤血球膜表面のホスファチジルセリン発現抑制剤。
[請求項9]
ヒスチジンリッチ糖タンパク質を赤血球含有溶液に添加することを特徴とする、赤血球膜表面のホスファチジルセリン発現抑制方法。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • Inventor
  • NISHIBORI, Masahiro
  • WAKE, Hidenori
  • ZHONG, Hui
  • MORI, Shuji
  • SAKAGUCHI, Masakiyo
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG

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