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Title:
TLR4 AGENT, TISSUE HOMEOSTASIS AGENT, HEPATOCYTE GROWTH FACTOR INDUCER, TISSUE REPAIRING AGENT, AND SIRTUIN INDUCER HAVING HYALURONIC ACID FRAGMENTS AS ACTIVE INGREDIENTS THEREOF
Document Type and Number:
WIPO Patent Application WO/2013/125634
Kind Code:
A1
Abstract:
 Provided are a TLR4 agent, a tissue homeostasis agent, a hepatocyte growth factor inducer, a tissue repairing agent, and a sirtuin inducer using hyaluronic acid fragments. Hyaluronic acid fragments selected from sizes of 2-20 sugar units, inclusive, or a pharmaceutically acceptable salt or solvate thereof, are used as the active ingredients of a TLR4 agent, a tissue homeostasis agent, a hepatocyte growth factor inducer, a tissue repairing agent, and a sirtuin inducer. The hyaluronic acid fragments are preferably hyaluronic acid fragments selected from sizes of 3-10 sugar units, inclusive, and more preferably are hyaluronic acid fragments of 3 or 4 sugar units.

Inventors:
ASARI AKIRA (JP)
CODEE JEROEN (NL)
Application Number:
PCT/JP2013/054330
Publication Date:
August 29, 2013
Filing Date:
February 21, 2013
Export Citation:
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Assignee:
HYALURONAN RES INST INC (JP)
International Classes:
A61K31/728; A23L1/30; A61K8/60; A61K8/73; A61K31/7016; A61K31/702; A61P3/04; A61P3/06; A61P3/10; A61P9/10; A61P9/12; A61P11/00; A61P13/12; A61P17/16; A61P19/02; A61P21/00; A61P25/00; A61P25/28; A61P29/00; A61P35/00; A61P43/00; A61Q19/08
Domestic Patent References:
WO2004084912A12004-10-07
WO2002074318A12002-09-26
WO2002004471A12002-01-17
WO2002004471A12002-01-17
Foreign References:
JPH09227386A1997-09-02
JP2007291133A2007-11-08
JP2006335694A2006-12-14
JP2006327959A2006-12-07
JP2006327958A2006-12-07
JP2007153761A2007-06-21
JP2007153766A2007-06-21
JP2007084509A2007-04-05
JP2008266171A2008-11-06
JP2009292767A2009-12-17
JPS6413008A1989-01-17
JP2007126453A2007-05-24
JP2010059084A2010-03-18
JPS5213733A1977-02-02
Other References:
HEPING XU, ET AL.: "Effect of Hyaluronan Oligosaccharides on the Expression of Heat Shock Protein 72", J. BIOL. CHEM., vol. 277, no. 19, 2002, pages 17308 - 17314, XP055082071
GHATAK S, ET AL.: "Hyaluronan Oligosaccharides Inhibit Anchorage-independent Growth of Tumor Cells by Suppressing the Phosphoinositide 3-Kinase/Akt Cell Survival Pathway", J. BIOL. CHEM., vol. 277, no. 41, 2002, pages 38013 - 38020, XP055010454
CHUNXUN ZENG, ET AL.: "INHIBITION OF TUMOR GROWTH IN VIVO BY HYALURONAN OLIGOMERS", INT. J. CANCER, vol. 77, 1998, pages 396 - 401, XP002523574
"ANGIOGENESIS INDUCED BY DEGRADATION PRODUCTS OF HYALURONIC ACID", SCIENCE, vol. 228, 1985, pages 1324 - 1326, XP008020551
GIUSEPPE M. CAMPO ET AL.: "Hyaluronan differently modulates TLR-4 and the inflammatory response in mouse chondrocytes", BIOFACTORS, vol. 38, no. 1, 30 January 2012 (2012-01-30), pages 69 - 76, XP055082074, Retrieved from the Internet [retrieved on 20130517]
JO MILNER: "Cellular Regulation of SIRT1", CURR. PHARM. DES., vol. 15, no. 1, January 2009 (2009-01-01), pages 39 - 44, XP008162710
JACK FORD ET AL.: "JNK2-dependent regulation of SIRT1 protein stability", CELL CYCLE, vol. 7, no. 19, 2008, pages 3091 - 3097, XP003032409
SCIENCE, vol. 228, 1985, pages 1324 - 1326
AKIRA ASARI: "Medical Application of Hyaluronan", 2004, ELSEVIER, article "Chemistry and Biology of Hyaluronan", pages: 457 - 473
GLYCOBIOLOGY, vol. 12, no. 7, 2002, pages 421 - 426
WALVOORT MT; VOLBEDA AG; REINTJENS NR; VAN DEN ELST H; PLANTE OJ; OVERKLEEFT HS; VAN DER MAREL GA; CODÉE JD: "Automated Solid-Phase Synthesis of Hyaluronan Oligosaccharides", ORG. LETT., vol. 14, no. 14, 2012, pages 3776 - 3779
KABRA N; LI Z; CHEN L; LI B; ZHANG X; WANG C; YEATMAN T; COPPOLA D; CHEN J: "SirT1 is an inhibitor of proliferation and tumor formation in colon cancer", J BIOL. CHEM., vol. 284, no. 27, 3 July 2009 (2009-07-03), pages 18210 - 7
SAMUEL SM; THIRUNAVUKKARASU M; PENUMATHSA SV; PAUL D; MAULIK N: "Akt/FOX03a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress in rat in vivo model of myocardial infarction: switching gears toward survival and longevity", J AGRIC. FOOD CHEM., vol. 56, no. 20, 22 October 2008 (2008-10-22), pages 9692 - 8
OTA H; ETO M; OGAWA S; IIJIMA K; AKISHITA M; OUCHI Y: "SIRT1/eNOS axis as a potential target against vascular senescence, dysfunction and atherosclerosis", JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS, vol. 17, no. 5, 2010, pages 431 - 435
CARTER S; MIARD S; ROY-BELLAVANCE C; BOIVIN L; LI Z; PIBAROT P; MATHIEU P; PICARD: "Sirt1 inhibits resistin expression in aortic stenosis", PLOS ONE, vol. 7, no. 4, 2012, pages E35110
SHAKIBAEI M; BUHRMANN C; MOBASHERI A: "Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappaB ligand (RANKL) activation of NF-kappaB signaling and inhibit osteoclastogenesis in bone-derived cells", J BIOL CHEM., vol. 286, no. 13, 1 April 2011 (2011-04-01), pages 11492 - 505
SINGH UP; SINGH NP; SINGH B; HOFSETH LJ; PRICE RL; NAGARKATTI M; NAGARKATTI PS: "Resveratrol (trans-3,5,4'-trihydroxystilbene) induces silent mating type information regulation-1 and down-regulates nuclear transcription factor-kappaB activation to abrogate dextran sulfate sodium-induced colitis", J PHARMACOL. EXP. THER., vol. 332, no. 3, March 2010 (2010-03-01), pages 829 - 39
DONMEZ G; WANG D; COHEN DE; GUARENTE L: "SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10", CELL, vol. 142, no. 2, 23 July 2010 (2010-07-23), pages 320 - 32, XP028931126, DOI: doi:10.1016/j.cell.2010.06.020
DONMEZ G: "The Effects of SIRT1 on Alzheimer's Disease Models", INT. J. ALZHEIMERS DIS. 2012, 2012, pages 509529
WANG P; XU TY; GUAN YF; TIAN WW; VIOLLET B; RUI YC; ZHAI QW; SU DF; MIAO CY: "Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway", ANN. NEUROL., vol. 69, no. 2, February 2011 (2011-02-01), pages 360 - 74
HERRANZ D; MUNOZ-MARTIN M; CANAMERO M; MULERO F; MARTINEZ-PASTOR B; FERNANDEZ-CAPETILLO 0; SERRANO M: "Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer", NAT. COMMUN., vol. 1, 12 April 2010 (2010-04-12), pages 3
KABRA N; LI Z; CHEN L; LI B; ZHANG X; WANG C; YEATMAN T; COPPOLA D; CHEN J: "SirT1 is an inhibitor of proliferation and tumor formation in colon cancer", J. BIOL. CHEM., vol. 284, no. 27, 3 July 2009 (2009-07-03), pages 18210 - 7
WU Z; LIU MC; LIANG M; FU J: "Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure", BLOOD, vol. 119, no. 10, 8 March 2012 (2012-03-08), pages 2422 - 9
HWANG JW; CHUNG S; SUNDAR IK; YAO H; ARUNACHALAM G; MCBURNEY MW; RAHMAN I: "Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism: implication in pathogenesis of COPD", ARCH. BIOCHEM. BIOPHYS., vol. 500, no. 2, 15 August 2010 (2010-08-15), pages 203 - 9, XP027136703
FAN H; YANG HC; YOU L; WANG YY; HE WJ; HAO CM: "The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury", KIDNEY INT., 9 January 2013 (2013-01-09)
JUNG YJ; LEE JE; LEE AS; KANG KP; LEE S; PARK SK; LEE SY; HAN MK; KIM DH; KIM W: "SIRT1 overexpression decreases cisplatin-induced acetylation of NF- B p65 subunit and cytotoxicity in renal proximal tubule cells", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 419, no. 2, 9 March 2012 (2012-03-09), pages 206 - 10, XP028466222, DOI: doi:10.1016/j.bbrc.2012.01.148
CHEN YR; LAI YL; LIN SD; LI XT; FU YC; XU WC: "SIRT1 interacts with metabolic transcriptional factors in the pancreas of insulin-resistant and calorie-restricted rats", MOL. BIOL. REP., 6 January 2013 (2013-01-06)
SHIOTA A; SHIMABUKURO M; FUKUDA D; SOEKI T; SATO H; UEMATSU E; HIRATA Y; KUROBE H; MAEDA N; SAKAUE H: "Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice", CARDIOVASC, DIABETOL., vol. 11, 8 November 2012 (2012-11-08), pages 139, XP021128998, DOI: doi:10.1186/1475-2840-11-139
MOON MH; JEONG JK; LEE YJ; SEOL JW; JACKSON CJ; PARK SY: "SIRT1, a class III histone deacetylase, regulates TNF-a-induced inflammation in human chondrocytes", OSTEOARTHRITIS CARTILAGE, vol. 21, no. 3, March 2013 (2013-03-01), pages 470 - 80
MATSUSHITA T; SASAKI H; TAKAYAMA K; ISHIDA K; MATSUMOTO T; KUBO S; MATSUZAKI T; NISHIDA K; KUROSAKA M; KURODA R: "The overexpression of SIRT1 inhibited osteoarthritic gene expression changes induced by interleukin-1? in human chondrocytes", J ORTHOP. RES., 9 November 2012 (2012-11-09)
KOK SH; LIN LD; HOU KL; HONG CY; CHANG CC; HSIAO M; WANG JH; LAI EH; LIN SK: "Simvastatin inhibits Cyr61 expression in rheumatoid arthritis synovial fibroblasts through the regulation of SIRT1/Fox03a signaling", ARTHRITIS RHEUM., 12 December 2012 (2012-12-12)
LIU B; GHOSH S; YANG X; ZHENG H; LIU X; WANG Z; JIN G; ZHENG B; KENNEDY BK; SUH Y: "Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria", CELL METAB., vol. 16, no. 6, 5 December 2012 (2012-12-05), pages 738 - 50
JOO HY; WOO SR; SHEN YN; YUN MY; SHIN HJ; PARK ER; KIM SH; PARK JE; JU YJ; HONG SH: "SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: implications for cell survival after irradiation", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 424, no. 4, 10 August 2012 (2012-08-10), pages 681 - 6
TONKIN J; VILLARROYA F; PURI PL; VINCIGUERRA M: "SIRT1 signaling as potential modulator of skeletal muscle diseases", CURR. OPIN. PHARMACOL., vol. 12, no. 3, June 2012 (2012-06-01), pages 372 - 6
CODOCEDO JF; ALLARD C; GODOY JA; VARELA-NALLAR L; INESTROSA NC: "SIRT1 regulates dendritic development in hippocampal neurons", PLOS ONE, vol. 7, no. 10, 2012, pages E47073
LI L; GAO P; ZHANG H; CHEN H; ZHENG W; LV X; XU T; WEI Y; LIU D; LIANG C: "SIRT1 inhibits angiotensin II-induced vascular smooth muscle cell hypertrophy", ACTA BIOCHIM. BIOPHYS. SIN. (SHANGHAI, vol. 43, no. 2, February 2011 (2011-02-01), pages 103 - 9
LI H; XU M; LEE J; HE C; XIE Z: "Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice", AM. J. PHYSIOL. ENDOCRINOL. METAB., vol. 303, no. 10, 15 November 2012 (2012-11-15), pages E1234 - 44
NISHIMURA EK; GRANTER SR; FISHER DE: "Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche", SCIENCE, vol. 307, no. 5710, 4 February 2005 (2005-02-04), pages 720 - 4, XP002456150, DOI: doi:10.1126/science.1099593
JOHNSON AC; HEINZEL FP; DIACONU E; SUN Y; HISE AG; GOLENBOCK D; LASS JH; PEARLMAN E: "Activation of toll-like receptor (TLR)2, TLR4, and TLR9 in the mammalian cornea induces MyD88-dependent corneal inflammation", INVEST. OPHTHALMOL. VIS. SCI., vol. 46, no. 2, February 2005 (2005-02-01), pages 589 - 95
TUON FF; FERNANDES ER; DUARTE MI; AMATO VS: "The expression of TLR2, TLR4 and TLR9 in the epidermis of patients with cutaneous leishmaniasis", J. DERMATOL. SCI., vol. 59, no. 1, July 2010 (2010-07-01), pages 55 - 7, XP027074841, DOI: doi:10.1016/j.jdermsci.2010.04.009
YUAN ZQ; BENNETT L; CAMPO MS; NASIR L: "Bovine papillomavirus type 1 E2 and E7 proteins down-regulate Toll Like Receptor 4 (TLR4) expression in equine fibroblasts", VIRUS RES., vol. 149, no. 1, April 2010 (2010-04-01), pages 124 - 7, XP026934664, DOI: doi:10.1016/j.virusres.2010.01.008
WANG X; BI Z; WANG Y; WANG Y: "Increased MAPK and NF- B expression of Langerhans cells is dependent on TLR2 and TLR4, and increased IRF-3 expression is partially dependent on TLR4 following UV exposure", MOL. MED. REPORT, vol. 4, no. 3, May 2011 (2011-05-01), pages 541 - 6
SAHIN H; BORKHAM-KAMPHORST E; DO 0 NT; BERRES ML; KALDENBACH M; SCHMITZ P; WEISKIRCHEN R; LIEDTKE C; STREETZ KL; MAEDLER K: "Proapoptotic effects of the chemokine, CXCL 10 are mediated by the noncognate receptor TLR4 in hepatocytes", HEPATOLOGY, 19 September 2012 (2012-09-19)
BAI T; LIAN LH; WU YL; WAN Y; NAN JX: "Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells", INT. IMMUNOPHARMACOL., vol. 15, no. 2, 12 January 2013 (2013-01-12), pages 275 - 281, XP028989532, DOI: doi:10.1016/j.intimp.2012.12.020
CAPIRALLA H; VINGTDEUX V; ZHAO H; SANKOWSKI R; AL-ABED Y; DAVIES P; MARAMBAUD P: "Resveratrol mitigates lipopolysaccharide- and A?-mediated microglial inflammation by inhibiting the TLR4/NF- B/STAT signaling cascade", J. NEUROCHEM., vol. 120, no. 3, February 2012 (2012-02-01), pages 461 - 72
OKUN E; BARAK B; SAADA-MADAR R; ROTHMAN SM; GRIFFIOEN KJ; ROBERTS N; CASTRO K; MUGHAL MR; PITA MA; STRANAHAN AM: "Evidence for a developmental role for TLR4 in learning and memory", PLOS ONE, vol. 7, no. 10, 2012, pages E47522
HUTCHINSON MR; ZHANG Y; BROWN K; COATS BD; SHRIDHAR M; SHOLAR PW; PATEL SJ; CRYSDALE NY; HARRISON JA; MAIER SF: "Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4", EUR. J. NEUROSCI., vol. 28, no. 1, July 2008 (2008-07-01), pages 20 - 9, XP002606196, DOI: doi:10.1111/J.1460-9568.2008.06321.X
LEE IT; SHIH RH; LIN CC; CHEN JT; YANG CM: "Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells", CELL COMMUN. SIGNAL., vol. 10, no. 1, 15 November 2012 (2012-11-15), pages 33, XP021121773, DOI: doi:10.1186/1478-811X-10-33
GOOD DW; GEORGE T; WATTS BA: "3rd ''Lipopolysaccharide directly alters renal tubule transport through distinct TLR4-dependent pathways in basolateral and apical membranes", AM. J. PHYSIOL. RENAL PHYSIOL., vol. 297, no. 4, October 2009 (2009-10-01), pages F866 - 74
PERROS F; LAMBRECHT BN; HAMMAD H: "TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways", RESPIR. RES., vol. 12, 24 September 2011 (2011-09-24), pages 125, XP021109851, DOI: doi:10.1186/1465-9921-12-125
SU HY; MO BW; WEI JH; HUANG JW; WANG CM; ZENG JR; XU Q; LIN Y: "Effect of TLR4 on the migration of asthmatic airway smooth muscle cells induced by airway epithelial cells", ZHONGGUO YING YONG SHENG LI XUE ZA ZHI, vol. 28, no. 2, March 2012 (2012-03-01), pages 103 - 6
FRANTZ S; KOBZIK L; KIM YD; FUKAZAWA R; MEDZHITOV R; LEE RT; KELLY RA: "Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium", J. CLIN. INVEST., vol. 104, no. 3, August 1999 (1999-08-01), pages 271 - 80
ZBINDEN-FONCEA H; RAYMACKERS JM; DELDICQUE L; RENARD P; FRANCAUX M: "TLR2 and TLR4 activate p38 MAPK and JNK during endurance exercise in skeletal muscle", MED. SCI. SPORTS EXERC., vol. 44, no. 8, August 2012 (2012-08-01), pages 1463 - 72
AKBARSHAHI H; AXELSSON JB; SAID K; MALMSTROM A; FISCHER H; ANDERSSON R: "TLR4 dependent heparan sulphate-induced pancreatic inflammatory response is IRF3-mediated", J. TRANSL. MED., vol. 9, 21 December 2011 (2011-12-21), pages 219, XP021130935, DOI: doi:10.1186/1479-5876-9-219
AWLA D; ABDULLA A; REGNÉR S; THORLACIUS H: "TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate", INFLAMM. RES., vol. 60, no. 12, December 2011 (2011-12-01), pages 1093 - 8
LI H; XU H; SUN B: "Lipopolysaccharide regulates MMP-9 expression through TLR4/NF- B signaling in human arterial smooth muscle cells", MOL MED REPORT, vol. 6, no. 4, October 2012 (2012-10-01), pages 774 - 8
WALVOORT MT; VOLBEDA AG; REINTJENS NR; VAN DEN ELST H; PLANTE OJ; OVERKLEEFT HS; VAN DER MAREL GA; COD6E JD: "Automated Solid-Phase Synthesis of Hyaluronan Oligosaccharides", ORG. LETT., vol. 14, no. 14, 2012, pages 3776 - 3779
SALMINEN A; KAARNIRANTA K.: "Genetics vs. entropy: longevity factors suppress the NF-kappaB-driven entropic aging process", AGEING RES. REV., vol. 9, no. 3, July 2010 (2010-07-01), pages 298 - 314
Attorney, Agent or Firm:
MATSUI SHIGERU (JP)
Shigeru Matsui (JP)
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