WO2013133440A1 - Inhibiteur de prolifération cellulaire et solution destinée à la conservation de cellules ou d'organes - Google Patents

Inhibiteur de prolifération cellulaire et solution destinée à la conservation de cellules ou d'organes Download PDF

Info

Publication number
WO2013133440A1
WO2013133440A1 PCT/JP2013/056632 JP2013056632W WO2013133440A1 WO 2013133440 A1 WO2013133440 A1 WO 2013133440A1 JP 2013056632 W JP2013056632 W JP 2013056632W WO 2013133440 A1 WO2013133440 A1 WO 2013133440A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
organ
niprl
cell
dilrg
Prior art date
Application number
PCT/JP2013/056632
Other languages
English (en)
Japanese (ja)
Inventor
鈴木　幸一
邦雄 今井
裕隆 勝崎
友紀 中条
順良 江幡
Original Assignee
国立大学法人岩手大学
国立大学法人三重大学
積水メディカル株式会社
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 国立大学法人岩手大学, 国立大学法人三重大学, 積水メディカル株式会社 filed Critical 国立大学法人岩手大学
Publication of WO2013133440A1 publication Critical patent/WO2013133440A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0205—Chemical aspects
    • A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
    • A01N1/0215—Disinfecting agents, e.g. antimicrobials for preserving living parts
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids

Definitions

  • the present invention relates to a cell growth inhibitor, a cell or organ preservation solution.
  • organ transplant surgery has been widely performed. If the organ damage in the patient is very large and recovery by normal treatment cannot be expected, the donor organ is transplanted to the recipient and treated.
  • the transplanted organ removed from the donor (donor) for the transplantation operation is in a state where the blood flow is interrupted and there is no supply of oxygen via the blood flow (ischemic state), and the transplantation takes several minutes to several hours. Saved.
  • the storage conditions such as the storage temperature and the storage solution may not be appropriately selected, or a long time may be required for transplantation.
  • a substrate or functional disorder may occur in the transplanted organ.
  • graft dysfunction may be observed due to microcirculatory disturbance with increased coagulation activity and thrombus formation after transplantation.
  • Such a disorder is generally called a post-ischemic reperfusion disorder of a transplanted organ.
  • organ preservation methods investigated methods for preventing these symptoms and preserving organs for transplantation in a physiologically favorable state.
  • the organ preservation methods reported to date are roughly classified into two methods: 1) perfusion method, and 2) simple immersion preservation method.
  • the perfusion method performs organ perfusion during the preservation period, supplies the cells with necessary oxygen and nutrients, and removes waste products, thereby maintaining organ metabolism and extending the preservation period.
  • organ preservation by the perfusion method involves various factors such as perfusion temperature, perfusion pressure, perfusion flow rate, and composition of the perfusate, and detailed optimum conditions have not been established.
  • the simple immersion preservation method is a method for preventing tissue damage due to oxygen deficiency by keeping organs at a low temperature and suppressing cell metabolism, and is widely used in clinical settings as a simple and effective method. ing. Specifically, a method is generally used in which blood components are washed from the blood vessel bed of the organ using a low-temperature preservation solution from an inflowing blood vessel or the like before or after the removal, and the extracted organ is immersed in the preservation solution.
  • Well-known organ preservation solutions include Eurocollins solution containing glucose and various electrolytes, and Wisconsin solution containing impermeable components, colloid osmotic pressure components, energy metabolism promoting components and hormones, respectively. It has been.
  • Eurocollins solution is effective for highly viable kidneys, but it is said that the protective effect on tissues and cells is not sufficient for organs other than kidneys, and Wisconsin solution is not suitable as a preparation. It is said to be stable and has the disadvantage of having to be stored at low temperatures after preparation.
  • Patent Documents 1, 2, and 3 various organ preservation solutions have been proposed (for example, Patent Documents 1, 2, and 3).
  • some of these organ preservation solutions have problems such as difficulty in preparation and homeostasis, and low solubility.
  • any of the above organ preservation solutions it is necessary to keep the organ at a low temperature, so that there is a fundamental problem that the functional recovery of the organ after transplantation is hindered. Furthermore, it has been pointed out as a point to be improved that a cooling device or the like is required and the burden of transporting the organ is large.
  • the present inventors have an amino acid sequence, aspartic acid-isoleucine-leucine-arginine-glycine (DILRG), and a C-terminal amidation in the research on Stherniidae's Antheraea yamamai.
  • DILRG aspartic acid-isoleucine-leucine-arginine-glycine
  • a novel peptide having a molecular weight of 570.96 has been found, and a patent has been obtained by clarifying the dormancy control action and cancer cell growth inhibitory action of this peptide (Patent Documents 4 and 5).
  • This peptide is also named “Yamamarin” by the present inventors.
  • Non-patent Document 1 a conjugate with palmitic acid (named “C16-Yamamarin”). ) Has been reported (Non-patent Document 1).
  • C16-DILRG-NH 2 C16-yamamarine
  • organ preservation solution containing C16-yamamarin as an active ingredient.
  • C16-yamamarine C16-DILRG-NH 2
  • C16-DILRG-NH 2 C16-yamamarine
  • DILRG-NH 2 yamamarine
  • solubility It is very low. Therefore, for example, when C16-yamamarin (C16-DILRG-NH 2 ) is applied to cell growth inhibitors and organ (cell) preservation solutions, an effective concentration of C16-yamamarin (C16-DILRG-NH 2 ) When a medium or a preservation solution containing it is prepared, an active ingredient (C16-Yamamarin (C16-DILRG-NH 2 )) may be precipitated, leaving room for further study in terms of practicality.
  • an object of the present invention is to provide a novel compound useful as an active ingredient of a cell growth inhibitor, a cell or organ preservation solution.
  • it prevents the occurrence of reperfusion injury after ischemia of the transplanted organ, and also provides an organ preservation solution that exhibits a sufficient preservation effect even if the preservation temperature of the organ is not lowered, and in particular, the active ingredient is a solution for use. It is an object to provide a highly practical organ preservation solution that does not precipitate in the medium.
  • the present invention provides the following compounds, cell growth inhibitors, cells or organ preservation solutions, and the like.
  • the acyl group preferably has 6 to 28 carbon atoms.
  • the acyl group preferably has 12 to 20 carbon atoms.
  • the acyl group preferably has 16 carbon atoms.
  • a cell growth inhibitor comprising the compound as an active ingredient.
  • the concentration of the active ingredient is preferably 0.1 ⁇ M to 1000 ⁇ M.
  • a method for preserving cells or organs comprising immersing cells or organs in the preservation solution.
  • the compound contained as an active ingredient in the preservation solution preferably has an acyl group having 6 to 28 carbon atoms.
  • the concentration of the active ingredient in the preservation solution is preferably 0.1 ⁇ M to 1000 ⁇ M.
  • the temperature of the preservation solution is preferably 5 to 37 ° C.
  • a cell culture method comprising culturing cells in a medium to which the cell growth inhibitor is added.
  • the cell growth inhibitor of the present invention can remarkably suppress cell growth. Therefore, the subculture interval can be changed flexibly, and further, the precipitation of active ingredients during use is suppressed and the handling is easy, so the labor of cell culture workers and the like can be significantly reduced. . Further, the preservation solution of the present invention is excellent in practicality because it can effectively and easily preserve cells or organs and suppresses the precipitation of active ingredients.
  • FIG. 6 is a graph confirming changes in cell growth inhibitory effect depending on the concentration of C16-NIPRL-NH 2 added to K562 cells and the number of culture days.
  • FIG. 6 is a graph comparing the growth inhibitory effects of C16-NIPRL-NH 2 , C16-DILRG-NH 2 (C16-Yamamarin), and DILRG-NH 2 (Yamamarin) on K562 cells.
  • N-terminal acylated NIPRL-NH 2 A novel peptide derivative (hereinafter sometimes referred to as N-terminal acylated NIPRL-NH 2 ) is useful as an active ingredient in a cell growth inhibitor, a cell or organ preservation solution, and the active ingredient is a solution. It was newly discovered that it does not precipitate in it.
  • This peptide derivative (N-terminal acylated NIPRL-NH 2 ) has a different basic skeleton (amino acid sequence) from that of conventional Yamamarin (DILRG-NH 2 ).
  • N-terminal acylated NIPRL-NH 2 is represented by the following chemical formula.
  • R in the formula represents an acyl group
  • this N-terminal acylated NIPRL-NH 2 has “asparagine-isoleucine-proline-arginine-leucine (NIPRL)” as a basic skeleton, and the C-terminal.
  • NIPRL-NH 2 can be synthesized by introducing an acyl group into the N-terminus of a peptide in which is amidated (hereinafter sometimes referred to as “NIPRL-NH 2 ”).
  • NIPRL-NH 2 a product produced by a known peptide synthesis method can be used, and it can also be obtained by other methods. However, in consideration of economy, mass productivity, etc., the peptide synthesis method Acquisition by is preferred.
  • the acyl group can be introduced by a known method.
  • the cell growth inhibitor of the present invention contains the above compound, N-terminal acylated NIPRL-NH 2 as an active ingredient.
  • the cells to be targeted by the cell growth inhibitor of the present invention are not particularly limited.
  • stem cells for example, stem cells, skin cells, mucosal cells, hepatocytes, pancreatic islet cells, nerve cells, chondrocytes isolated from human or non-human animal tissues , Including endothelial cells, epithelial cells, bone cells, muscle cells, and further, sperm of animals such as livestock and fish, eggs or fertilized eggs, insect cells, plant cells and the like.
  • the cell growth inhibitor of the present invention is, for example, an appropriate amount for cells cultured in a known medium (Iskov modified Dulbecco medium, Iskov medium, RPMI medium, Dulbecco MEM medium, MEM medium, F12 medium, etc.) For example, a final concentration of about 0.1 ⁇ M to 10 mM) can be used.
  • the amount of addition of the cell growth inhibitor of the present invention can be appropriately set in consideration of the type of cultured cells and the period during which cell growth should be suppressed.
  • various other known components can be added on the condition that the growth inhibitory activity is not inhibited.
  • Specific examples include components such as penicillin, streptomycin, sodium pyruvate, vitamins, amino acids, thioglycerol, calcium chloride, and serum albumin.
  • the cell growth inhibitor of the present invention By using the cell growth inhibitor of the present invention, it is possible to suppress the growth of cultured cells and flexibly change the interval of subculture, so that the labor of cell culture workers and the like can be significantly reduced. .
  • the cell growth inhibitor of the present invention can be used even when the concentration of the cell growth inhibitor in the medium is set to a range suitable for culture.
  • the active ingredient (N-terminal acylated NIPRL-NH 2 ) is prevented from being precipitated, is easy to handle, and can be cultured in a suitable environment, so that the labor of cell culture workers and the like is further reduced.
  • the cell or organ preservation solution of the present invention contains the above compound, N-terminal acylated NIPRL-NH 2 as an active ingredient.
  • the N-terminal acylated NIPRL-NH 2 reversibly suppresses the oxygen consumption of cells and organs, the Yamamarin (DILRG-NH 2 ) or C16-Yamamarin (C16-DILRG-NH 2 ) Is based on the same mechanism (see Patent Document 6).
  • the preservation solution of the present invention is prepared as a solution containing N-terminal acylated NIPRL-NH 2.
  • N-terminal acylated NIPRL-NH 2 For example, when a transplanted organ is preserved, the organ is immersed in the preservation solution during the preservation period. By reducing the consumption and removing the organ from the preservation solution before transplantation, the oxygen consumption of the organ can be returned to normal again. Therefore, organ damage caused by oxygen deficiency can be prevented.
  • N-terminal acylated NIPRL-NH 2 is a very short small molecule with 5 amino acids as the skeleton of the chemical structure. For example, it is easy to prepare a stock solution and maintain homeostasis. . In addition, it can be stored at room temperature, has excellent storability and handleability, and can be stored for a long time.
  • the concentration of N-terminal acylated NIPRL-NH 2 in the preservation solution is, for example, in the range of 0.1 ⁇ M to 1000 ⁇ M, preferably 1 ⁇ M to 100 ⁇ M. It is preferable to do this.
  • the cells to be stored with the preservation solution of the present invention are not particularly limited, and include, for example, various cells exemplified as the target of the cell growth inhibitor.
  • the organs that are the target of the preservation solution of the present invention are not particularly limited, and examples include skin, blood vessels, cornea, kidney, heart, liver, umbilical cord, intestine, nerve, lung, placenta, pancreas, and the like.
  • the preservation solution of the present invention can be composed of N-terminal acylated NIPRL-NH 2 alone.
  • one or two or more of the components generally incorporated in organ preservation solutions can be incorporated. it can.
  • components that can be blended in the preservation solution of the present invention for example, sugars such as glucose, maltose, sucrose, lactose, raffinose, trehalose, mannitol, hydroxyethyl starch, pullulan, gluconic acid, lactic acid, Organic acids such as acetic acid, propionic acid, ⁇ -hydroxybutyric acid, citric acid, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, hydrogen phosphate Electrolytes such as dipotassium, sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, vitamins such as L-ascorbic acid and vitamin E, amino acids such as glycine
  • the preservation solution of the present invention can be used in combination with known organ preservation solutions such as Eurocollins solution and Wisconsin solution, thereby improving the organ preservation ability and practicality of conventional organ preservation solutions. You can also be used in combination with known organ preservation solutions such as Eurocollins solution and Wisconsin solution, thereby improving the organ preservation ability and practicality of conventional organ preservation solutions. You can also be used in combination with known organ preservation solutions such as Eurocollins solution and Wisconsin solution, thereby improving the organ preservation ability and practicality of conventional organ preservation solutions. You can also
  • the preferable application temperature as a condition for using the preservation solution of the present invention is 5 to 37 ° C, particularly preferably 25 to 37 ° C. Since the preservation solution of the present invention does not necessarily need to preserve an organ at a low temperature as in the prior art, the function of the organ after transplantation is smoothly restored. Of course, there is a problem of functional recovery in organ transplantation, but the temperature of the preservation solution can be lowered (for example, 5 ° C. or lower), and in this case, cells and organs can be preserved for a longer period of time. .
  • the concentration of the active ingredient (N-terminal acylated NIPRL-NH 2 ) in the preservation solution is set to a range suitable for organ preservation, the active ingredient (N Since the precipitation of terminal acylated NIPRL-NH 2 ) is suppressed, it is excellent in handleability and practicality.
  • N-terminal acylated NIPRL-NH 2 (NIPRL peptide with N-terminal acylation and C-terminal amidation) Peptide synthesizer (PSSM-8, manufactured by Shimadzu Corporation) used, N-terminal free on the resin by conventional methods, protecting groups (NH 2) with peptide: asparagine - isoleucine - proline - arginine - were synthesized leucine -NH 2 (NIPRL-NH 2) .
  • the peptide resin is suspended in a mixed solvent of dimethylformamide (DMF) and pyridine, and palmitic acid (C16 carboxylic acid) and WSCD (1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride) are added at room temperature. Stir overnight. After completion of the reaction, the resin was collected by filtration and washed with DMF and methanol. The acylated peptide resin thus obtained was cut off and cocktail-treated by a conventional method, and crude N-terminal acylated NIPRL-NH 2 (C16-NIPRL-) having an acyl group having 16 carbon atoms (palmitoyl group) at the N-terminus. NH 2 ) was obtained.
  • DMF dimethylformamide
  • WSCD 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride
  • acylation of the peptide resin with the mixture of palmitic acid and WSCD performed here can also be achieved by treatment with the corresponding carboxylic acid chloride (palmitoyl chloride).
  • the peptide is mixed with an equal amount of matrix (saturated with 40% acetonitrile / 0.1% TFA ⁇ -CHCA) on the sample plate, dried, and structured by MALDI-TOF MS (Discovery, manufactured by Shimadzu Corporation) It was confirmed.
  • palmitoyl group is introduced to the N-terminal by introducing palmitoyl group (acylation), and C16-NIPRL- NH 2 can also be synthesized.
  • the molecular weight of C16-NIPRL-NH 2 was 849.16.
  • peptide derivatives used in the following examples were synthesized by the same method as described above by appropriately changing the peptide chain of the basic skeleton and the acylating reagent. Specifically, for comparison with C16-NIPRL-NH 2, Yamamarin (DILRG-NH 2) and N-terminal acylated Yamamarin (C6, C10, C16- DILRG- NH 2) other, the following peptide derivatives Synthesized.
  • Penetratin-DILRG-NH 2 Compound in which the C-terminal of a peptide having an amino acid 16-residue sequence of “RQIKIWFQNRRMKWKK” is acid amide-bonded to the N-terminal of DILRG-NH 2
  • Oligoarginine-DILRG-NH 2 A compound in which a peptide C-terminal having the 10-residue amino acid sequence of “RRRRRRRRRR” is acid amide-bonded to the N-terminal of DILRG-NH 2 ⁇ Reference: Biochemistry (Vol. 81, No.
  • AHPN-DILRG-NH 2 and AHPN-FGPRL-NH 2 (3) AHPN-DILRG-NH 2 and AHPN-FGPRL-NH 2 : AHPN (6- (3- (1-Adamantyl) -4-hydroxyphenyl) -2-naphtalene carboxylic acid) is converted to DILRG-NH 2 or FGPRL-NH Compound with acid amide bond to N-terminal of 2
  • K562 chronic myelogenous leukemia
  • RPMI1640 with 10% FBS
  • K562 CML, chronic myelogenous leukemia
  • FBS FBS
  • a K562 cell solution at a concentration of 1 ⁇ 10 5 Cell / mL into a 96-well microplate at 100 ⁇ L / well
  • each of the peptide derivatives was treated with yamamarin (DILRG-NH 2 ) is dissolved in phosphate buffer, and other peptide derivatives are dissolved in DMSO, adjusted to the final concentration (described in Table 1 below), and 10 ⁇ L of yamamarin (DILRG-NH 2 ) is added to each well.
  • peptide derivatives were added at 0.5 ⁇ L. After culturing at 37 ° C. and 5% CO 2 for 48 hours, the number of cells was measured using a Premix WST-1 reagent (manufactured by Takara Bio Inc.). That is, after directly adding 10 ⁇ L of Premix WST-1 reagent to each well, the mixture was reacted at 37 ° C. under 5% CO 2 for 1 hour, and the absorbance was measured at 450/620 nm.
  • Premix WST-1 reagent manufactured by Takara Bio Inc.
  • the number of cells was measured using a Premix WST-1 reagent (Takara Bio Inc.). That is, after directly adding 10 ⁇ L of Premix WST-1 reagent to each well, the mixture was reacted at 37 ° C. under 5% CO 2 for 1 hour, and the absorbance was measured at 450/620 nm.
  • NHDF normal human skin fibroblasts
  • NHDF dedicated medium manufactured by LIFELINE
  • Yamamarin DILRG-NH 2
  • DMSO DMSO
  • Premix WST-1 reagent manufactured by Takara Bio Inc.
  • the number of cells was measured using Premix WST-1 reagent (manufactured by Takara Bio Inc.). That is, after directly adding 10 ⁇ L of Premix WST-1 reagent to each well, the mixture was reacted at 37 ° C. under 5% CO 2 for 2 hours, and the absorbance was measured at 450/620 nm.
  • the number of cells was measured using a Premix WST-1 reagent (manufactured by Takara Bio Inc.). That is, after directly adding 10 ⁇ L of Premix WST-1 reagent to each well, the mixture was reacted at 37 ° C. under 5% CO 2 for 1 hour, and the absorbance was measured at 450/620 nm. 3 days after addition of DILRG-NH 2 (Yamamarin) 10 mM, C16-DILRG-NH 2 (C16-Yamamarin) 25 ⁇ M, C16-NIPRL-NH 2 : 0.1 ⁇ M, 1 ⁇ M, 10 ⁇ M, 25 ⁇ M (all final concentrations) The cell growth control effect on the cells was compared.
  • a Premix WST-1 reagent manufactured by Takara Bio Inc.
  • FIG. 1 is a graph confirming the change in cell growth inhibitory effect depending on the concentration of C16-NIPRL-NH 2 added to K562 cells and the number of culture days.
  • C16-NIPRL-NH 2 showed a concentration of several percent at 1 ⁇ M and 50% at 10 ⁇ M on the third day after addition.
  • %, 25 ⁇ M it was found that the cell growth inhibitory effect was about 75%. It was also found that when the addition concentration was 25 ⁇ M, the cell growth inhibitory effect appeared significantly from the first day of addition, and the effect persisted for at least 3 or 4 days (FIG. 1).
  • FIG. 2 is a graph comparing the growth inhibitory effects of C16-NIPRL-NH 2 , C16-DILRG-NH 2 (C16-Yamamarin), and DILRG-NH 2 (Yamamarin) on K562 cells.
  • C16-NIPRL-NH 2 was used at the same concentration as C16-DILRG-NH 2 (C16-Yamamarin) (25 ⁇ M)
  • it exhibited a cell growth inhibitory effect that was about twice as high.
  • the cell growth inhibitory effect of C16-NIPRL-NH 2 is shown as about 20% increase of DILRG-NH 2 (Yamamarin), but when converted from the fact that the concentration of Yamamarin used is 10 mM.
  • C16-NIPRL-NH 2 is, DILRG-NH 2 (Yamamarin), C16-DILRG-NH 2 compared to (C16-Yamamarin), to exhibit cytostatic at low concentrations was found (Fig. 2) .
  • C16-DILRG-NH 2 and C16-NIPRL-NH 2 were added at the same effective concentration (12.5 ⁇ M) to three commonly used media, C16-DILRG-NH 2 was in culture. In the NHDF dedicated medium, crystal precipitation was observed, but C16-NIPRL-NH 2 showed no crystal precipitation in any medium. Therefore, when C16-NIPRL-NH 2 is used at an effective concentration, it does not precipitate crystals in the medium in the normal medium compared to C16-DILRG-NH 2 during cultivation, and is highly practical. Was confirmed.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Dentistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un nouveau composé représenté par la formule chimique (1) utilisé comme principe actif d'un inhibiteur de prolifération cellulaire et comme solution destinée à la conservation de cellules ou d'organes.
PCT/JP2013/056632 2012-03-09 2013-03-11 Inhibiteur de prolifération cellulaire et solution destinée à la conservation de cellules ou d'organes WO2013133440A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012-053798 2012-03-09
JP2012053798A JP5900921B2 (ja) 2012-03-09 2012-03-09 細胞増殖抑制剤、細胞または臓器の保存液

Publications (1)

Publication Number Publication Date
WO2013133440A1 true WO2013133440A1 (fr) 2013-09-12

Family

ID=49116907

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/056632 WO2013133440A1 (fr) 2012-03-09 2013-03-11 Inhibiteur de prolifération cellulaire et solution destinée à la conservation de cellules ou d'organes

Country Status (2)

Country Link
JP (1) JP5900921B2 (fr)
WO (1) WO2013133440A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3023790B1 (ja) * 1999-05-31 2000-03-21 農林水産省蚕糸・昆虫農業技術研究所長 遺伝子Ａｎｙ―ＲＦならびに休眠制御物質およびその製造方法
JP3579711B2 (ja) * 2000-03-22 2004-10-20 独立行政法人農業生物資源研究所 ガン細胞増殖抑制剤
JP2010239963A (ja) * 2009-03-19 2010-10-28 Iwate Univ 細胞または臓器の保存液および保存方法
JP2011051916A (ja) * 2009-08-31 2011-03-17 Iwate Univ 昆虫の休眠卵誘導剤、昆虫の休眠卵産出方法および害虫の防除方法
JP2011051917A (ja) * 2009-08-31 2011-03-17 Iwate Univ Ｆｉｂｒｉｌｌａｒｉｎ保有細胞増殖抑制剤

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3023790B1 (ja) * 1999-05-31 2000-03-21 農林水産省蚕糸・昆虫農業技術研究所長 遺伝子Ａｎｙ―ＲＦならびに休眠制御物質およびその製造方法
JP3579711B2 (ja) * 2000-03-22 2004-10-20 独立行政法人農業生物資源研究所 ガン細胞増殖抑制剤
JP2010239963A (ja) * 2009-03-19 2010-10-28 Iwate Univ 細胞または臓器の保存液および保存方法
JP2011051916A (ja) * 2009-08-31 2011-03-17 Iwate Univ 昆虫の休眠卵誘導剤、昆虫の休眠卵産出方法および害虫の防除方法
JP2011051917A (ja) * 2009-08-31 2011-03-17 Iwate Univ Ｆｉｂｒｉｌｌａｒｉｎ保有細胞増殖抑制剤

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
KEN TATEISHI ET AL.: "Konchu Baiyo Saibokabu o Mochiita C16-Yamamarin no Amino-san Chikantai no Kentei", HEISEI 22 NENDO SANSHI KONCHU KINO RIYO GAKUJUTSU KOENKAI, THE JAPANESE SOCIETY OF SERICULTURAL SCIENCE DAI 80 KAI KOEN YOSHISHU, vol. 80, 2010, pages 37, 219 *
MASAKATSU KAMIYA: "Structure-activity relationship of a novel pentapeptide with cancer cell growth-inhibitory activity", JOURNAL OF PEPTIDE SCIENCE, vol. 16, no. 5, 2010, pages 242 - 248 *
PING YANG ET AL.: "A palmitonyl conjugate of an insect pentapeptide causes growth arrest in mammalian cells and mimics the action of diapause hormone", JOURNAL OF INSECT BIOTECHNOLOGY AND SERICOLOGY, vol. 76, 2007, pages 63 - 69 *
YOSINORI SATO ET AL.: "A palmitoyl conjugate of insect pentapeptide Yamamarin arrests cell proliferation and respiration", PEPTIDES, vol. 31, 2010, pages 827 - 833 *

Also Published As

Publication number Publication date
JP2013184957A (ja) 2013-09-19
JP5900921B2 (ja) 2016-04-06

Similar Documents

Publication Publication Date Title
KR101061293B1 (ko) 허혈 예방을 위한 보호 용액
JP2006115837A (ja) 細胞凍結保存用組成物
JPH089521B2 (ja) 極洋の魚類から単離および精製された熱ヒステリシスタンパク質
KR100855354B1 (ko) 관류세척 보존 용액
JP6027300B2 (ja) 細胞または臓器の保存液および保存方法
US9055739B2 (en) Compositions for cryopreservation of cells
US20050233299A1 (en) Method for preserving organs for transplantation with a HGF-containing solution
CN110495450B (zh) 一种细胞冻存运输液及其应用
KR20210143833A (ko) Dmso가 없는 동결 보존액 및 그 제조방법과 응용
US20160302406A1 (en) Organ preservation and/or perfusion
JP2006306821A (ja) 細胞・組織の凍結障害防止液及び凍結保存法
CA3057214A1 (fr) Nouveaux procedes de surrefrigeration pour la conservation d'echantillons biologiques
KR20200118422A (ko) 동결보존용 조성물 및 이의 사용 방법
CN111418580A (zh) 干细胞冻存液及冻存方法
EP3685665A1 (fr) Conservation de cellules souches
JP5900921B2 (ja) 細胞増殖抑制剤、細胞または臓器の保存液
JP5771376B2 (ja) 細胞増殖抑制剤、細胞または臓器の保存液
WO2008127959A1 (fr) Utilisation de l'ergothionéine et/ou de ses dérivés pour conserver les cellules
Komatsu et al. Oxygenated thawing and rewarming alleviate rewarming injury of cryopreserved pancreatic islets
WO2021183653A1 (fr) Compositions pour prolonger la conservation viable et la durée de conservation d'organes et de tissus
Tomalty et al. Chilling injury in human kidney tubule cells after subzero storage is not mitigated by antifreeze protein addition
JP2008094752A (ja) 生体材料を保護する機能を有するペプチド
KR102463256B1 (ko) 카페인 등을 이용한 지방조직 저온 또는 동결 보관용 조성물 및 이를 이용한 지방 조직의 보관 방법
AU2006349615B2 (en) Organ preservation and/or perfusion
WO2024018051A1 (fr) Compositions de plasmine stables pour la conservation et le reconditionnement d'organes

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13758060

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13758060

Country of ref document: EP

Kind code of ref document: A1