【WO2019201701A1】用作生物分子递送或吸附系统的肌醇六磷酸盐【专利】

((51)International Patent Classification:A61K47/00(2006.01)A61K39/00(2006.01)A61K31/6615(2006.01)(21)International Application Number:PCT/EP2019/059078(22)International Filing Date:10April2019(10.04.2019)(25)Filing Language:English(26)Publication Language:English(30)Priority Data:18167427.616April2018(16.04.2018)EP(71)Applicant:CRODA DENMARK A/S[DK/DK];Elsen-bakken23,3600Frederikssund(DK).(72)Inventors:DUROUX,Laurent;Hvalsovej42A2tv.,2700Bronshoj(DK).LINDBLAD,Erik;FrederiksbergAlle19B.3.sal tv.,1820Frederiksberg(DK).(74)Agent:KARFOPOULOS,Alexis;Croda Europe Limit¬ed,Cowick Flail,Snaith,Goole,East Yorkshire DN149AA(GB).(81)Designated States(unless otherwise indicated,for everykind o f national protection available):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.(84)Designated States(unless otherwise indicated,for everykind o f regional protection available):ARIPO(BW,GH,GM,KE,LR,LS,MW,MZ,NA,RW,SD,SL,ST,SZ,TZ,UG,ZM,ZW),Eurasian(AM,AZ,BY,KG,KZ,RU,TJ,TM),European(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,Cl,CM,GA,GN,GQ,GW,KM,ML,MR,NE,SN,TD,TG).Published:—with international search report(Art.21(3))(54)Title:PHYTATES FOR USE AS A BIOMOLECULES DELIVERY OR ADSORPTION SYSTEM(57)Abstract:The present invention relates to mineral micro-particles comprising phytate(inositol hexaphosphate,IP6).More partic¬ularly,the invention provides salts of phytic acid with multivalent metal ions such as Ca+and Mg+for use in biomolecules delivery or adsorption systems,methods for their production and uses thereof,such as for use as a vaccine adjuvant..PHYTATES FOR USE AS A BIOMOLECULES DELIVERY OR ADSORPTION SYSTEMTECHNICAL FIELDThe present invention relates t o mineral micro-particles comprising phytate and one or more multivalent cations M+,M3+or organic polycations.More particularly,the invention provides such mineral micro-particles for use in biomolecules delivery or adsorption systems,such as for use as vaccine adjuvants.BACKGROUND O F THE INVENTIONMineral adjuvants,such as aluminum-containing adjuvants,including aluminum phosphate,aluminum hydroxide and calcium phosphate,have been used successfully for decades t o enhance the immune response against killed,inactivated and subunit vaccine antigens.Aluminum adjuvants are,at present,the most widely used adjuvants in both veterinary and human vaccines.Calcium phosphate has so far only been used t o a limited extent as an adjuvant in commercial veterinary vaccines,but has been used as an adjuvant in vaccines against diphtheria,tetanus, Bordetella pertussis and poliomyelitis(Relyveld,1986;Coursaget et al.,1986),commercialised by Institut Pasteur.Calcium phosphate was also used as an adjuvant in the I PAD series of vaccines by Institut Pasteur for approx.25years.Further,calcium phosphate has been tested as an adjuvant in experimental vaccines with the gpl60antigen from H IV(Relyveld and Chermann,1994).Both aluminium hydroxide and calcium phosphate have been used as adjuvants in commercialised adsorbed allergen preparations for hyposensitization of allergic patients(Relyveld et al.,1985).This application is particularly interesting,partly because allergic patients develop antigen-specific IgE type antibodies,which can lead t o mast cell degranulation and anaphylaxia.With the calcium phosphate adjuvant,the literature data suggest that this adjuvant does not give lead t o significant stimulation of IgE antibodies.Vassilev(Vassilev,1978)compared t o the reaction in terms of passive cutaneous anaphylaxia(PCA)in guinea pigs after two immunizations with either aluminium or calcium phosphate adjuvant using tetanus toxoid as antigen.It was found that calcium phosphate treated guinea pigs only had insignificant IgE titres compared t o the group that had received Al-adjuvanted vaccines.The research in this field is however sparse and there are at present no data on the interleukin profile after immunization with calcium phosphate t o illustrate possible underlying differences in the mechanisms behind such a difference.。