WO2004054594A1 - Inhibiteur de mort cellulaire - Google Patents

Inhibiteur de mort cellulaire Download PDF

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Publication number
WO2004054594A1
WO2004054594A1 PCT/JP2003/015412 JP0315412W WO2004054594A1 WO 2004054594 A1 WO2004054594 A1 WO 2004054594A1 JP 0315412 W JP0315412 W JP 0315412W WO 2004054594 A1 WO2004054594 A1 WO 2004054594A1
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WO
WIPO (PCT)
Prior art keywords
cell death
group
milt
cells
fish
Prior art date
Application number
PCT/JP2003/015412
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English (en)
Japanese (ja)
Inventor
Hiroaki Hirata
Seiji Shioda
Atsushi Takaki
Hirokazu Otaki
Masaji Matsunaga
Original Assignee
Nissan Chemical Industries, Ltd.
Nissei Bio Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nissan Chemical Industries, Ltd., Nissei Bio Co., Ltd. filed Critical Nissan Chemical Industries, Ltd.
Priority to AU2003303051A priority Critical patent/AU2003303051A1/en
Publication of WO2004054594A1 publication Critical patent/WO2004054594A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a substance having an inhibitory effect on late neuronal cell death caused by ischemia.
  • DNA and ribonucleic acid are macromolecules that are present in all living cells and preserve the genetic information of living organisms.
  • Nucleotides, which are constituents of these nucleic acids are also constituents of ATP, which is an energy source of living organisms, cAMP and cGMP, which are metabolic regulators, and NAD and FAD, which are enzymatic enzymes. Plays an important role in Nevertheless, the nutritional value of nucleic acids has received little attention until recently. However, recently, it has been reported that the intake of nucleic acids or nucleotides affects cell development, immune function, brain function, lipid metabolism, etc. (for example, Chandra, RK & Kumari, S.
  • Nutrition compositions for infants which are obtained by blending a ground material and a fractionated product, are known. It has been reported that the nutritional composition can be expected to have effects such as improvement of convenience, improvement of nitrogen use efficiency, improvement of absorption and absorption ability, suppression of onset of allergy, promotion of intestinal maturation, etc. by taking it. (For example, see Japanese Patent Application Laid-Open No. 8-238720, page 2.)
  • the brain is composed of nerve cells connected to each other via neurites. And if the connection between nerve cells is broken, it takes time, but the neurites can regenerate and reconnect and recover brain function, but if the nerve cells themselves are damaged and die, the nerve cells will Unlike other cells, they do not divide and reproduce, so brain function is not restored. It is also known that nerve cells in the brain are very vulnerable to ischemia. For example, somatic cells, such as limbs, eventually recover after reperfusion without blood flow for several hours, but cerebral ischemia can cause neuronal death in as little as 5 minutes, leading to serious sequelae. is there.
  • the excellent phagocytic effect of the milt extract of fish has been recognized, the details of the effect have not been elucidated yet, and no particular study has been made on the effect of suppressing cell death. It is presumed that the effect of milt extract is derived from its main component, protamine, a kind of nucleic acid and nucleoprotein, but if the details of the neurological effect can be elucidated, The timing, amount, etc. can be optimized, and a synergistic effect with other drugs can be expected, and the efficacy of the milt extract is expected to be significantly extended.
  • the present invention has been made in view of the above problems, and its object is to first clarify the details of the cranial neurological effect of a milt extract containing nucleic acid and protamine as main components, and to provide a more effective Finding uses. Another object is to provide a cell death inhibitor as understood from the description in the present specification and a food containing the same. Disclosure of the invention
  • the present inventors have conducted intensive studies and have found that a fish milt extract rich in nucleic acid and protamine can significantly suppress cell death, particularly nerve cell death.
  • the fish is a cell death inhibitor according to the first aspect, wherein the fish is selected from the group consisting of salmon, trout, and herring.
  • the cell death inhibitor according to the first aspect which is used for suppressing delayed neuronal death
  • the cell death inhibitor according to the third aspect which is used for suppressing delayed neuronal death caused by ischemia
  • a food comprising an effective amount of the cell death inhibitor according to the first to fourth aspects.
  • FIG. 1 is a graph illustrating the survival rate up to 7 days after ischemia for 25 minutes in the NF group and the NP group according to Test Example 1.
  • Figure 2 shows the hippocampus in which uninjured cells were stained with toluidine blue under an optical microscope according to Test Example 2.
  • Figures 2A and 2C show the NF group, and Figures 2B and 2D. Indicates the NP group.
  • FIG. 3 is a diagram showing the hippocampus in which TUNEL-stained cells damaged like apoptosis were enlarged by an optical microscope according to Test Example 2, and FIG. 3A and FIG. 3C show the NF group, and FIG. B and FIG. 3D show the NP group.
  • FIG. 4 is a schematic cross-sectional view of the hippocampus illustrating a region in which the number of cells was measured in Test Example 2.
  • the cytostatic agent of the present invention comprises an effective amount of a fish milt extract.
  • the fish milt extract of the present invention contains a nucleic acid and protamine which is a protein in a nucleoprotein as main components.
  • nucleic acids There are two types of nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), which store genetic information of living organisms. And among the fish milts are adenine (A), thymine (T), It contains a large amount of DNA consisting of four nucleotides, guanine (G) and cytosine (C). There have been reports in recent years that the intake of nucleic acids, including DNA, helps to improve the health of living organisms. However, prior to the present invention, it was unclear what effect would be exerted on living organisms.
  • Protamine is a basic protein that is abundant in milt of fish and binds to nucleic acids to form nucleoprotamine.
  • the arginine content is high, and nitrogen derived from arginine is equivalent to 25 to 90% of the total nitrogen content.
  • the fish milt extract of the present invention is produced, for example, by removing skin, muscle, blood vessels, etc. from fish milt and then purifying the same.
  • examples of the fish preferably include salmon, trout, herring, and ⁇ .
  • milt of fish such as salmon, trout, herring and ⁇ was used only for edible use, and most of them were discarded without being used.
  • the manufacturing cost can be reduced.
  • by treating with protease and nuclease it can be made water-soluble.
  • the cell death inhibitor of the present invention can be in various dosage forms.
  • a dosage form such as a powder, a granule, a tablet or a capsule can be obtained.
  • the water-solubilized product may be a solution or the like.
  • the cell inhibitor of the present invention can effectively suppress cell death caused by various factors.
  • the cell inhibitor of the present invention can effectively suppress cell death that occurs in cells at various sites due to ischemia, a phenomenon in which blood does not flow to cells.
  • the site include terminal sites such as a heart and a fingertip, a kidney, a penis, and the like.
  • the cell death inhibitor of the present invention increases ischemia by increasing blood flow in cells at these sites. Inhibit cell death due to In particular, the cell death inhibitor of the present invention is effective against delayed neuronal cell death in the brain after ischemia / reperfusion in stroke or the like and cell death in the heart due to ischemia in myocardial infarction or the like.
  • the cell death inhibitor in an amount of about 0.1 to 10 g, preferably 0.2 to 5 g per day, and it is administered once to three times a day.
  • the dosage may vary depending on the age, weight, and symptoms.
  • a cell death inhibitor comprising a milt extract of fish is added to food.
  • a cell death inhibitor comprising a milt extract of fish is added to food.
  • a milt extract was purified from salmon milt as follows.
  • the suspension was filtered to remove solids such as milt skin, and then spray-dried with a spray dryer to obtain a powdery substance.
  • This powdery substance was washed with ethanol to remove ethanol-soluble matter and water, and dried under reduced pressure to obtain 180 g of a powdered milt extract.
  • the milt extract obtained by force was a pale yellow powder, and its chemical and physical properties are shown below.
  • a water-soluble milt extract was prepared as follows.
  • Example 1 After the temperature of the suspension obtained in 1. of Example 1 was raised to 50 ° C., 0.1% of the milt was treated with PYN 3.0 (manufactured by Novo Nordisk Bioindustry Co., Ltd.). S, Main component: Contains trypsin from porcine stalks and trace amounts of chymotrybun. 1 g was added and reacted for 4 hours with stirring. During the reaction, the pH of the reaction solution was maintained at 6.0 to 6.3. No heating was performed during the reaction, and after 4 hours, the temperature of the reaction solution dropped to 44.7 ° C. After the reaction was completed, the temperature of the reaction solution was raised to 70 ° C. to inactivate the protease.
  • PYN 3.0 manufactured by Novo Nordisk Bioindustry Co., Ltd.
  • S Main component: Contains trypsin from porcine stalks and trace amounts of chymotrybun. 1 g was added and reacted for 4 hours with stirring. During the reaction, the pH of the reaction solution was maintained at
  • nuclease 0.1% of milt manufactured by Amano Pharmaceutical Co., Ltd., nuclease “Amano”, isolated from Penicilliumcitrinum bacteria. 1 g
  • the pH of the reaction solution was maintained at 5.0 to 5.5.
  • the temperature of the reaction solution was raised to 85 ° C to inactivate the nuclease.
  • the reaction was cooled to 35 ° C and the pH was adjusted to 7.0.
  • the reaction solution was continuously sent to a decanter to separate the supernatant, and the separated supernatant was sprayed with a spray dryer and dried to obtain 130 g of a powdery milt extract.
  • the nerve cell death inhibitory effect of the group to which the milt extract of Example 1 was administered (NP group) was evaluated as compared to the group to which the milt extract was not administered (the NF group). This effect is not limited to the milt extract of Example 1, but also applies to the milt extract of Example 2 which has been made water-soluble by enzymatic treatment with protease and nuclease.
  • Table 1 shows the composition of the feed given to each group.
  • Vitamin mixture 1.0 1.0
  • mice Six week old C57BL / 6 mice were used for the experiment. The mice are first maintained on a 12 hour light cycle, 23 ⁇ 2 ° C, 40 ⁇ 15% relative humidity on a normal diet and then for 7 days on the above diet corresponding to each experimental group. Then, experiments were performed.
  • the targeted neuronal cell death is a delayed neuronal cell death in the hippocampus that occurs after cerebral ischemia and reperfusion, and is caused by occluding both common carotid arteries in mice for a certain period of time and then reperfusion.
  • Test example 1 The targeted neuronal cell death is a delayed neuronal cell death in the hippocampus that occurs after cerebral ischemia and reperfusion, and is caused by occluding both common carotid arteries in mice for a certain period of time and then reperfusion.
  • the inhibitory effects on neuronal cell death were compared between the NF group and NP group of mice that had delayed neuronal cell death due to occlusion for 15 minutes.
  • FIG. 2 is a diagram showing the state of toluidine blue staining, wherein FIGS. 2A and 2C show the NF group, and FIGS. 2B and 2D show the NP group.
  • the scale bar is 400 ⁇ in FIGS. 2A and 2B, and 100 ⁇ m in FIGS. 2C and 2D.
  • FIG. 3 is a diagram showing the state of TUNEL staining, and FIGS. 3A and 3C show the NF group, and FIGS. 3B and 3D show the NP group.
  • the scale bar is the same as in Figure 2.
  • the number of cells stained with toluidine blue in the NF group was 18.4 on average, and the number of cells stained with TUNEL was 29.2 on average.
  • the number of cells stained with toluidine blue was 35.7 on average, and the number of cells stained with TUNEL was 9.3 on average.
  • one effect of a fish milt extract has been clarified by finding that a fish milt extract, whose effect was not known at all, is useful for suppressing cell death. Based on this, it is possible to optimize the target, timing, and amount of prescription, and to use it in combination with other drugs, thereby significantly increasing the effectiveness of milt extract.
  • the milt extract of the present invention also has an effect of promoting the blood flow of cells, and thus is useful not only for the nerve cells of the brain but also for the increase of the blood flow in the heart, fingertips, kidney, penis and the like.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
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  • Marine Sciences & Fisheries (AREA)
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  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
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  • Obesity (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention a trait à un inhibiteur de mort cellulaire caractérisé en ce qu'il contient un extrait de laitance comprenant des acides nucléiques et de la protamine en tant que principaux ingrédients. De préférence, cet inhibiteur de mort cellulaire est produit à partir d'un poisson choisi parmi le groupe constitué du saumon, de la truite, du hareng et de la morue. Il est notamment d'utilisation appropriée pour l'inhibition de mort de cellules nerveuses prolongée provoquée par l'ischémie.
PCT/JP2003/015412 2002-12-18 2003-12-02 Inhibiteur de mort cellulaire WO2004054594A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003303051A AU2003303051A1 (en) 2002-12-18 2003-12-02 Cell death inhibitor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002366637A JP2004196701A (ja) 2002-12-18 2002-12-18 細胞死抑制剤
JP2002-366637 2002-12-18

Publications (1)

Publication Number Publication Date
WO2004054594A1 true WO2004054594A1 (fr) 2004-07-01

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AU (1) AU2003303051A1 (fr)
WO (1) WO2004054594A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014202834A1 (fr) * 2013-06-18 2014-12-24 University Of Helsinki Protamine pour le traitement de lésions neuronales

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007117014A (ja) * 2005-10-28 2007-05-17 Nissan Chem Ind Ltd 関節リウマチ症予防のための栄養補助食品
JP5820127B2 (ja) * 2011-02-17 2015-11-24 フォーデイズ株式会社 アミロイド線維の形成を伴う神経変性疾患の予防・改善薬
KR20170001567A (ko) 2015-06-26 2017-01-04 주식회사 파마리서치프로덕트 어류의 정액 또는 정소로부터 분리된 dna 단편 혼합물을 포함하는 허혈성 장염의 예방 또는 치료용 조성물
KR102234367B1 (ko) * 2020-09-07 2021-03-31 바이오메디팜 어업회사법인 주식회사 연어의 정소로부터 고순도 피디알엔의 추출 방법

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0164036A1 (fr) * 1984-05-26 1985-12-11 Nissan Chemical Industries Ltd. Composition pour accélérer la récupération de la fonction des organes hématopoiétiques et son application
EP0216133A1 (fr) * 1985-08-16 1987-04-01 Nissan Chemical Industries Ltd. Agent de nutrition pour le système nerveux cérébrospinal
JPH0551325A (ja) * 1991-04-19 1993-03-02 Morinaga Milk Ind Co Ltd 神経成長因子産生促進剤
JPH08165246A (ja) * 1994-12-10 1996-06-25 Nisshoku Corp 生理活性促進剤ならびに生理活性促進カプセル剤
JPH08187059A (ja) * 1994-06-06 1996-07-23 J One Prod Kk 核酸食品の製造方法
JPH10215828A (ja) * 1997-02-04 1998-08-18 Nisshin Oil Mills Ltd:The 活性酸素種消去剤
JPH10218781A (ja) * 1997-02-04 1998-08-18 Nisshin Oil Mills Ltd:The 体調調整剤
JP2000169386A (ja) * 1998-12-10 2000-06-20 Sarude Yakuhin Kk 免疫機能賦活剤及び飲食物
WO2001012201A1 (fr) * 1999-08-12 2001-02-22 Alexandr Vilenovich Asafov Composition remplacant le plasma sanguin
JP2001061484A (ja) * 1999-06-23 2001-03-13 Sankyo Co Ltd アポトーシス抑制活性を有するポリヌクレオチド
JP2002350274A (ja) * 2001-05-25 2002-12-04 Ykk Architectural Products Inc サッシ性能予測方法およびサッシ性能予測プログラム
JP2003235504A (ja) * 2002-02-13 2003-08-26 Marino Forum 21 耐久力増強剤
JP2003335664A (ja) * 2002-05-15 2003-11-25 Fukumi Morishige アルギニンとｒｎａを含有する脳脊髄系神経栄養剤

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0164036A1 (fr) * 1984-05-26 1985-12-11 Nissan Chemical Industries Ltd. Composition pour accélérer la récupération de la fonction des organes hématopoiétiques et son application
EP0216133A1 (fr) * 1985-08-16 1987-04-01 Nissan Chemical Industries Ltd. Agent de nutrition pour le système nerveux cérébrospinal
JPH0551325A (ja) * 1991-04-19 1993-03-02 Morinaga Milk Ind Co Ltd 神経成長因子産生促進剤
JPH08187059A (ja) * 1994-06-06 1996-07-23 J One Prod Kk 核酸食品の製造方法
JPH08165246A (ja) * 1994-12-10 1996-06-25 Nisshoku Corp 生理活性促進剤ならびに生理活性促進カプセル剤
JPH10218781A (ja) * 1997-02-04 1998-08-18 Nisshin Oil Mills Ltd:The 体調調整剤
JPH10215828A (ja) * 1997-02-04 1998-08-18 Nisshin Oil Mills Ltd:The 活性酸素種消去剤
JP2000169386A (ja) * 1998-12-10 2000-06-20 Sarude Yakuhin Kk 免疫機能賦活剤及び飲食物
JP2001061484A (ja) * 1999-06-23 2001-03-13 Sankyo Co Ltd アポトーシス抑制活性を有するポリヌクレオチド
WO2001012201A1 (fr) * 1999-08-12 2001-02-22 Alexandr Vilenovich Asafov Composition remplacant le plasma sanguin
JP2002350274A (ja) * 2001-05-25 2002-12-04 Ykk Architectural Products Inc サッシ性能予測方法およびサッシ性能予測プログラム
JP2003235504A (ja) * 2002-02-13 2003-08-26 Marino Forum 21 耐久力増強剤
JP2003335664A (ja) * 2002-05-15 2003-11-25 Fukumi Morishige アルギニンとｒｎａを含有する脳脊髄系神経栄養剤

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MATSUNAGA M ET AL: "Nucleoprotamine diet derived from salmon soft roe protects mouse hippocampal nerons from delayed cell death after transient forebrain ischemia", NEUROSCI. RES., vol. 47, no. 3, November 2003 (2003-11-01), pages 269 - 276, XP002981584 *
MATSUNAGA M: "Tokushu apoptosis to hifu kagaku gaiinsei nucleotide (kakusan) ni yoru apoptosis ni yudo", FARAGRANCE JOURNAL, vol. 26, no. 6, 1998, pages 81 - 87, XP002981586 *
TAKAGI A ET AL: "Kaku-tanpakushitsu ga mouse zenno kyoketsugo no kaiba chihassei shinkei saiboshi o yobo suru", NIHON SHINKEI KAGAKU TAIKAI PROGRAM - SAROKUSHU, vol. 25, July 2002 (2002-07-01), pages 254, XP002981585 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014202834A1 (fr) * 2013-06-18 2014-12-24 University Of Helsinki Protamine pour le traitement de lésions neuronales
EP3010524A4 (fr) * 2013-06-18 2017-01-18 University of Helsinki Protamine pour le traitement de lésions neuronales
US9896488B2 (en) 2013-06-18 2018-02-20 University Of Helsinki Protamine in treatment of neuronal injuries
US10160791B2 (en) 2013-06-18 2018-12-25 University Of Helsinki Protamine in treatment of neuronal injuries

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AU2003303051A8 (en) 2004-07-09
JP2004196701A (ja) 2004-07-15

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