»
`
`dy
`
`,
`
`CN 101468214
`
`© TXPCNEA / EPOCN101468214 A 20090701
`
`The presentinventi n relates to a kind of Deuterated water f r ophthalmological operation, also relateto its
`preparation method.A kind of Deuterated water for ophthalmological operation is characterized in that, it is 100%
`perfluorodecalin.Its preparation methodis to be the complete airtight synthetic rectification purification then that raw
`material carries out perfluorodecalin with naphthalene+hydrogenated naphthalene and naphthalane.Perfluorodecalin
`proportion is more than 1.9, and is safe and reliable as Deuterated water for ophthalmological operation, has n_
`side
`effect.
`
`A kind of Deuterated water for ophthalmological operation and preparation method thereof
`Technical field
`The present invention relates to a kind of Deuterated water for ophthalmological operation, also relate to its
`preparation method.
`Background technology
`Vitrectomy" operation abbreviation " Bo Qie "; conventional vitrectomy operation is that three 1.5 millimeters otch is
`done at 3-4 millimeter place behind eye cornea; form the ophthalmic illuminator by special optical fibers; at the
`microscopically of fine definition; utilize cutting head that vitreous excision is also extracted out; utilize gas
`r heavy
`water that the retina pressing is resetted again, and endolaser sealing ceasma reachesretina and resets.
`Summary of the invention
`The first aspect of purpose of the present invention is to propose a kind of Deuterated water for ophthalmological
`operation.
`Akind of Deuterated water for ophthalmological operation is characterized in that, it is 100% perfluorodecalin.
`Perfluorodecalin proportion is more than 1.9, and is safe and reliable as Deuterated water for ophthalmological
`operation, has no side effect.
`The second aspectof purposeof the present invention is topropose the preparation method of this Deuterated water
`for ophthalmological operation.
`Akind of method for preparing above-mentioned Deuterated water for ophthalmological operation is characterized in
`that, may further comprise the steps:
`A, in1 stage reactor, add potassium hydrogen fluoride, adopt 80 °C ~ 100 °C heating to react, the nascentstate
`fluorine that producesis directly put into 2 grades of catalytic reactors and is directly made cobalt trifluoride with the
`metailic cobalt reaction, and heating makescatalytic reactor temperature reach 200 °C ~ 300 °C;
`B, get naphthalene and be dissolved in the vaporizer thatfills hydrogenated naphthalene, the weightratio of
`naphthalene and hydrogenated naphthalene is 1:4~1:7, the mixed solution evaporation back of naphthalene and
`hydrogenated naphthalene is added in the reactor vaporizer heating with gaseous form, and productis collected in
`the crude product container;
`Behind c, reinforced the finishing, through distilled water wash, the desiccant drying gets thick product
`perfluorodecalin with gleanings in the crude product container, and reflux in 20% KOH alcoholic solution till the
`solution pH value is greater than 12, after leaving standstill, is told lower floor, drying;
`D, carry out molecule rectification purification through the dried crude product perfluorodecalin of alkali cleaning with
`dephlegmator with above-mentioned, dephlegmatoris madefiller with recording wire, theoretical cam curve 49 ~65,
`3.07 centimetres/plate of theoretical layer height, use the GC trace analysis in the distillation process, 140 °C ~142 °C
`collections of control temperature are the perfluorodecalin elaboration;
`E, the perfluorodecalin elaboration filtered with Seitz filter after, be sub-packedin the special vial.
`The preparation method of Deuterated water for ophthalmological operation of the present invention, productive rate
`height, the purity height of the perfluorodecalin that obtains.
`The specific embodiment
`For technological means, creation characteristic that the present invention is realized, reach purpose and effectis
`easy to understand, below in conjunction with the specific embodiment, further set forth the present invention.
`Deuterated water for ophthalmological operation of the present invention is a kind of fluorocarbons, fluorocarbons of
`a greatvariety, the synthesis technique method f purification has nothing in commonwith each other, can produce
`different chemical compounds accordingt different synthesis conditi ns, perfluorodecalin of the present invention,
`with regard to 140~142°C_ fits boiling p ints, proportionis m re than 1.9,andthem lecular formula of
`perfluorodecalin is C in the enf rcement 10 F 18 ,m Jecular weight is 462.
`
`Page |
`
`19.02.2018 19:44:02
`
`

`

`f Deuterated waterf rophthalmol gical operation of the present inventi nis 100%
`The raw material
`perfluor decalin, is to be that the complete airtight synthetic and rectification purificati nthat raw material carries ut
`perfluorodecalin makes with naphthalenet+thydrogenated naphthalene and naphthalane, and chemical equati nis as
`follows:
`
`t.
`CN101468214
`c
`
`EM1I309937200-idf0001
`
`EMI1309937200-idf0002
`
`Concrete preparation methodis as follows:
`A, in1 stage reactor, add potassium hydrogen fluoride, adopt 80 °C ~100 °C heating to react, the nascent state
`fluorine that producesis directly put into 2 grades of catalytic reactors and is directly made cobalt trifluoride with the
`metallic cobalt reaction, and heating makes catalytic reactor temperature reach 200 °C ~ 300 °C;
`B, get naphthalene and be dissolved in the vaporizer thatfills hydrogenated naphthalene, the weightratio of
`naphthalene and hydrogenated naphthalene is 1:4~ 1:7, the mixed solution evaporation back of naphthalene and
`hydrogenated naphthalene is added in the reactor vaporizer heating with gaseous form, and productis collected in
`the crude product container;
`Behind c, reinforced the finishing, through distilled water wash, anhydrous sodium sulfate drying gets thick product
`perfluorodecalin with gleanings in the crude product container, and reflux in the 20%KOHalcoholic solution till the
`solution pH value is greater than 12, after leaving standstill, is told lower floor, drying;
`D, carry out molecule rectification purification through the dried crude product perfluorodecalin of alkali cleaning with
`dephlegmator with above-mentioned, dephlegmator is made filler with recording wire, theoretical cam curve 49~65,
`3.07 centimetres/plate of theoretical layer height, use the GC trace analysis in the distillation process, 140 °C ~142 °C
`collections of control temperature are the perfluorodecalin elaboration;
`E, the perfluorodecalin elaboration filtered with Seitz filter after, be sub-packed in the special vial.
`Perflu rodecalin is to determine according to its inherent physicochemical property as the application of Deuterated
`water for ophthalmological operation.Fluorination reaction temperature, the time of interpolation, the ratio that feeds
`intake etc.are all influential to the productive rate of perfluorodecalin, are dissolved intmethod of hydrogen
`naphthalene with naphthalene, can avoid the reinforced difficulty of solid, and can make course of reaction be difficult
`for pr ducing overheated and cruelly towards phenomenon.Makethat output, the quality of product are all very
`_ Stable, its action principleis:
`1, surface tension is little, and the adhesion of building becauseof the perfluorodecalin molecule is low, so surface
`tension is little, is about 1/4th of water.
`2, than great, density is high,
`The Main physical of perfluorodecalin, chemical property parameter are:
`1, molecular formula: C 10 F 18
`2, molecular weight: 462
`3, proportion: >) 1.9g/cm <3 > 25 °C
`4,b iling point: 140~142
`5, surface tension: <20mN/m
`6, viscosity: 2.66mPa.s
`7, xygen solubility: >} =45 (25 °C £ 0.5 °C Vo1%).
`8, carbon dioxide dissolubility: ) =150 (25 °C +0.5 °C Vo1%).
`9, chemical constitution:
`
`EMI309937200-idf0003
`
`Emb diment1
`
`2,akind of meth df rpreparing the described Deuterated water for ophthalmological operation of claim 1 is
`characterized in that, may further comprise the steps:
`
`Page 2
`
`19.02.2018 19:44:02
`
`

`

`CN101468214
`
`react, the nascentstate fluorine of
`A, add p _tassium hydrogen fluoride in 1 stage reactor,ad pt80°C fheatingt
`generati nis directly put into 2 grades of catalytic reactors and is directly made cobalttrifluoride with the metallic
`c balt reaction, and heating makescatalytic reactor temperature reach 200 °C;
`B, get naphthalene and bedissolved in the vaporizerthatfills hydrogenated naphthalene, the weight ratio of
`naphthalene and hydrogenated naphthaleneis 1:4, the mixed solution evaporation back of naphthalene and
`hydrogenated naphthalene is addedin the reactor vaporizer heating with gaseous form, and productis collected in
`the crude product container;
`,
`Behind c,reinforced the finishing, through distilled water wash, anhydrous sodium sulfate drying gets thick pr duct
`perfluorodecalin with gleanings in the crude product container, and reflux in the 20%KOH alcoholic solution till the
`s lution pH value is greater than 12, after leaving standstill, is told lowerfloor, drying;
`D, carry out molecule rectification purification through the dried crude product perfluorodecalin of alkali cleaning with
`dephlegmator with above-mentioned, dephlegmatoris madefiller with recording wire, theoretical cam curve 49~65,
`3.07 centimetres/plate of theoretical layer height, use the GC trace analysis in thedistillation process, 140 °C ~ 142 °C
`collections of control temperature are the perfluorodecalin elaboration;
`E, the perfluorodecalin elaboration filtered with Seitz filter after, be sub-packed in the special vial.
`Embodiment 2
`2, akind of method for preparing the described Deuterated water for ophthalmological operation of claim 1 is
`characterized in that, may further comprise the steps:
`A, add potassium hydrogen fluoride in 1 stage reactor, adopt 100 °C of heating to react, the nascent state fluorine of
`generationis directly put into 2 grades of catalytic reactors and is directly made cobalttrifluoride with the metallic
`cobalt reaction, and heating makescatalytic reactor temperature reach 300 °C;
`B, get naphthalene and be dissolvedin the vaporizer thatfills hydrogenated naphthalene, the weightratio of
`naphthalene and hydrogenated naphthaleneis 1:7, the mixed solution evaporation back of naphthalene and
`hydrogenated naphthaleneis added in the reactor vaporizer heating with gaseous form, and productis collected in
`the crude product container;
`Behind c,reinforced the finishing, through distilled water wash, anhydrous sodium sulfate drying gets thick product
`perfluorodecalin with gleanings in the crude product container, and reflux in the 20%KOHalcoholic solutiontill the
`solution pH value is greater than 12, after leaving standstill, is told lower floor, drying;
`D, carry out molecule rectification purification throughthe dried crude product perfluorodecalin of alkali cleaning with
`dephlegmator with above-mentioned, dephlegmatoris madefiller with recording wire, theoretical cam curve 49 ~65,
`3.07 centimetres/plate of theoretical layer height, use the GC trace analysisin the distillation process, 140 °C ~142 °C
`collections of control temperature are the perfluorodecalin elaboration;
`E, the perfluorodecalin elaboration filtered with Seitz filter after, be sub-packedin the special vial.
`More than show and described ultimate principle of the present invention, principal character and advantage of the
`present invention.The technical staff of the industry should understand; the present invention is not restricted to the
`described embodiments; that describes in the foregoing description and the description justillustrates principle of the
`present invention; the present invention also has various changes and modifications without departing from the spirit
`and scopeofthe present invention, and these changes and improvementsall fall in the claimed scope of the invention.
`The claimed scope of the present invention is defined by appending claims and equivalent thereof.
`
`[Claims]
`1,a kind of Deuterated water for ophthalmological operation is characterized in that, it is 100% perfluorodecalin.
`2, akind of method for preparing the described Deuterated water for ophthalmological operation of claim 1 is
`characterized in that, may further comprise the steps:
`A, in1 stage reactor, add potassium hydrogen fluoride, adopt 60 °C ~120 °C heating to react, the nascent state
`flu rine that producesis directly put into 2 grades of catalytic reactors and is directly made cobalt trifluoride with the
`metallic cobalt reaction, and heating makes catalytic reactor temperature reach 150 °C ~350 °C;
`B, get naphthalene and be dissolved in the vaporizer thatfills hydrogenated naphthalene, the weight ratio f
`naphthalene and hydrogenated naphthalene is 1:1~1:10, the mixed solution evaporation back of naphthalene and
`hydrogenated naphthaleneis added in the react rvap rizer heating with gase us form, and pr ductis collected in
`the crude product c ntainer;
`
`Page 3
`
`19.02.2018 19:44:02
`
`

`

`Behindc, reinf rced the finishing, through distilled water wash, the desiccant drying gets thick pr duct
`perfiuor decalin with gleanings in the crude pr duct container, and reflux in 20% KOH alc holics luti n till the
`s luti n pH valueis greater than 12, after leaving standstill, is told lowerfloor, drying;
`D, carry out molecule rectification purification thr ugh the dried crude product perfluorodecalin of alkali cleaning with
`dephlegmator with above-menti ned, dephiegmat ris madefiller with recording wire, theoretical cam curve 49 ~65,
`3.07 centimetres/piate of theoretical layer height, use the GC trace analysis in the distillation process, 140 °C~ 142 °C
`c llections of control temperature are the perfluorodecalin elaboration;
`E, the perfluorodecalin elaboration filtered with Seitz filter after, be sub-packed in the special vial.
`
`CN101468214
`3
`
`Page 4
`
`19.02.2018 19:44:02
`
`

`

`[19] HEREMEBER
`
`.
`
`a
`>
`
`s
`
`AN 43
`
`.
`
`[21] His= 200710173379. 6
`
`[51] Int. Cl.
`A61L 31/00 (006.01 )
`CO7C 17/12 @006. 01 )
`
`
`[43] FAA 2009477 51H
`
`[11] HF= CN 1014682144
`
`[22] RIGA 2007. 12.27
`[21] HiS= 200710173379. 6
`[71] BigA _LEET RAAES A]
`
`§=200237 EET ARE BIR TIT ST.
`font
`pe
`[72] aA & ft
`
`[74] Seley LRAOR REA BS
`al
`IBA FR ab
`
`BAY EEKAG1 GL PLAS 6
`
`[54] HAZE
`— Fh AB}PAR A Ht akBe Hl AH TIE
`[57] f=
`AS FCA Be — FPAE PAR BK, Ee A EL fil]
`eri. = PARA} SP OR BK, JOR EAE TT. SLA
`100% HIA he.|IAG TIE AE LAE + SUR
`
`Fe bt A SRS EFT4 ZS ot WY oe eA GRJ
`atk,
`AP RUZEREEKHEZE 1.9 DA kK. EER RIF AR A
`
`KRAZE SE, Tm.
`
`

`

`200710173379.6
`
`Mm A Ee hk
`
`SL/1R
`
`1, —PPIRRP ARBk, SORRGEZEF, BOA 100% HIMAEKE.
`
`2. ApeSCAB 1 PTIAMERBEARD KAY, FORRGEZET. fade
`
`LX PR 2b ae:
`
`a. 7E 1 RIRWAAMARMILA, KAY 60°C~120°C NWT RPV, PEE
`
`BES RARMA 2 RELRNE PSSeRVARS=abe, DO
`
`AEHEC Be DVaiidEIA BI) 150°C ~350°C;
`
`b. RAATRAALANA, RSA ELE 1: 1~1: 10,
`
`KS 2SBeAsIMHS FO ULE IEARWASTERARA, DY
`
`POUPAA ih ASE FP
`
`cy WEG Ha, REL Aas ACERZEAEBAR, FERRIPIER, FAH=
`
`Meas, TE 20%KOH CRAP OAS, EAM pH (AF 12 ALE,
`
`Hea, 2th Fla, Pies
`
`da HFRABEAIRJes EA ch SeSRC SDPREEAT3}FGA,
`
`PUREDAAR, He 49~65, HIRE 3.07 BOK, FELT
`
`HW GC FRR, PERIE 140°C~142CIKE, BIN SRAGOAL,
`
`ec. HemaDAR RENE, DETR
`
`

`

`200710173379. 6
`
`it
`
`BA a
`
`1/65
`
`— FHAREF AR A 7kA SE
`
`RAK th
`
`AS BWA Be—BRRALP ARS BK, KEEReHETIE
`
`BmRiza
`
`EASE” PORTER “BOD” , FSRBP REZE_A BRAAR 3-4
`
`SEA= 1.5 SKIN, TREHl 6 SAEE IR PY RR AAS, CET
`
`MRE eee P, AAIRAR, BR ARH
`
`ARES P Shc,
`
`IRA ROGASSL, AFL bo RIA BI) 5Sfiz.
`
`AMAA
`
`AB AC AR) ES 8 — aTZEB Hs —ABPR Bk
`
`—PREP ORBK, SORRECET. HA 100%H EMAC.
`
`ERASETE LODE, FAIRERAB KRE HSE, FCRIE.
`
`AB AC AAA SS BSS AyTE TBE HY PPRPRA BK IBI
`
`—AP BeERAPORBUKIT, FORRMIEZET.
`
`fUdBLL RRR:
`
`a, TE 1 BIRWANALSE, SRA 80°C~100°C WFAWET RO, FREI
`
`PERMEIRMA 2 REM P SSRWARISa, Ie
`
`HEM, BeWatiinFEIKFl] 200°C ~300°C;
`
`b. RAATRHALANARe, RAABBW 1: 4~1: 7,
`
`15 ARBCMEASA UAC IEBR BJs WAASBA RRA, RY
`
`FUSE FAB ihBS
`
`

`

`200710173379. 6
`
`ui
`
`WW B 2/enm
`
`. DVBSEH IS, HRA SeRK, PRAIA, TE
`
`niceeaebt, FE 20%KOH CAAPA, BERK pH fhAF 12 W1E,
`
`HES. WHER, FR:
`
`ds KF ERAREFBR Jes BAB is ZeASIC 2DCREDE ToDPO, 2
`
`FELISPAN 2 VEAL, FRORe 49~65, FRIAE 3.07 EKA, HERE
`
`HH GC BRERAHT, PEM RE 140°C~ 142°C, EDNAASOR AG
`
`ec, EPRAOE Th AE RYRAEYEA. oePe elBP
`
`AS AC AA TAR AORBP ORKIS TIE, POR, SIARH AL
`
`—
`Bm.
`
`Aikist
`
`Ay EAS Fe AA SEERAER. BU VPRETE. AREA WSTH TA,
`
`FRASH ASHER, BEAR
`
`AROS RR URALER kKPLA, RLRES,
`
`AMIERATIESAH, HERRARAHAERAN, AR
`
`BAW ASRASKE, BEALWE A 140~142°C, LEHEZE 1.9 DILL, Seiieh-eameewEny
`Ft CFigs BFE 462.
`
`ASACB BRR HUBBEER BakRL 100%2MBEBE, FEWIZE+ SUL EER
`
`Hehe hy BURLUETTEEA ASARAL, HRst
`
` KH>P3 BaAGEBe F,+ Coq?CoF3
`
`OO + OCHSHeo
`
`APRll0 F
`
`

`

`200710173379. 6
`
`ui
`
`WW B 33/6m
`
`a,7E 1 RRMA ARIA, RA 80°C~100°C NFARETT RY, PRE
`
`HW eVER RABMA 2 SHER +S eae RWaISSbh, DO
`
`AL HEAL, Be SV ailBEIK Bl] 200°C ~300°C;
`
`b. RAVATRAALRMBRE, BAAN BELA 1: 4~1: 7,
`
`HAE BeAS EAR PU SUE IEARa WASTE A Re eA, I DY
`
`PBTFA AAS
`
`c. ESE, Ai AAURDA ARB KYOIR, FOKMRIATHE,
`
`HAPs iheAe,FE 20%KOH CRA POA at, EAM pH(AKF 12 4
`
`ik, #Be, TUTE, Fee:
`
`dy EXRASGRETFIRIE HEL isSROdPEE ATODORL,
`
`FEA ANE ESE), BELCHER 49~65, PRIOR ES 3.07 BOKAR, FATE
`
`HF GC BRERA)BT, FEHIYARE 140°C~142 CK, APMC :
`
`ce. BERMASO ih ARIEIE. ATaA
`
`GEE ARAL ARA KASA, RB BEAPETRE
`
`AULROOEBE, MSPORIN TA), BORAT ECBITARCHIeM, DAS
`
`ARF+E, FREE DUES AE, TidBBEDEA BP et
`
`ARRUMMA. PET MMB. AY+e. HERB:
`
`1, RMKA), APMAMATAHMAAAIC, PORK, AK
`
`KID az
`
`2. thAY im,
`
`SRAEB. WAFERSRA:
`
`1. FsK: CF is
`
`

`

`200710173379. 6
`
`uo
`
`HW
`
`OB B4/onm
`
`2. FH: 462
`
`3, EKH: >1.9g/em?
`
`25°
`
`4, Wi: 140~142
`
`5. #iHsK57: <20mN/m
`
`6, #iH: 2.66mPa.s
`
`7. FURR: 245 (25C405C Vol%).
`
`8. —SULBAAERE: 2150 (25°C+0.5C Vol%).
`
`9.AZ:
`
`CFLE)
`
`SE UEP1
`
`2. RSOBES 1 PIA ERRISERAKIA, SORPEET, te
`
`LAFRR:
`
`ar FEL RRMA AIARCS, SAY 80°C DOFNRET RO, PAE BITEAS
`
`PARMA 2 SERPS SRERNAS=LE, DORE he
`
`DaeYlEIABI] 200°C ;
`
`b. RRATRAALRNARE HT, BHAA BLOW 1: 4, ARR
`
`dtMREASFURNES TERIMARA, Bee
`
`SRTAH i BS
`
`cy INESEHRIS, KA AR ASRKR, FOER78
`
`KAP" in eee, FE 20%KOH CRAPA, EBA pH (PAT 12 4
`
`ik, ES, ai Pe, Tees
`
`

`

`200710173379. 6
`
`uo OB OB5/om
`
`d. KEIRAREFER JS BY 48h AeSAREFEST 9FO,
`
`
`EUR GAA (ESE, HOSRH 49~65, HORE 3.07 SOKA, FTE
`
`HAN GC ERERSoT, PERI140°C~142°C, BDA SARoA
`
`e, RPASO an A Ee YRSEEa, STOR rlAAP
`
`SEWEP 2
`
`2. FH llAP SESE 1 AR ARBER BOK, REET a
`
`ELF ER:
`
`a, HEL RRMA DARL, SRR 100°C DUETRB. PPAR TE
`
`ARBBMA2RHRV PSSBH RMARSSMC, DOREHE
`
`J PYASUEIA Fl 300°C ;
`
`b. MARAT RARLANAREH, BSAARR1: 7, BRR
`
`28NEVES ALAR NRABR ER a UATEAee A, BU AUC
`
`STASE
`
`|
`
`c. DUELSEHEI, HAA AASAe8ERR, FTO7KRA,
`
`APAeA,ZE20%KOH ZARAAl, BBA pH(AAT 12 4
`
`ik, Ba, Aw bE, PRR;
`
`d. KfEARGUEFER OA oeAR EETDO,
`
`FECATT22 (EIB, FEVOPSA 49~65, HECRie= 3.07 BOK, FateTS
`
`HF GC ERERAHT, FERRE 140C~142CKE, ASMAGA:
`
`e, BRERAGeH LSE EAE, 2M TRel BRIA
`
`DA _b Se aSANI TAS BE EASRB SEIE PNRAR. ANAT
`
`

`

`200710173379. 6
`
`ui
`
`WW B Be/enm
`
`PBRATAMIA TAR, AS RBA ANSEEIR SEHEA BRB, LS SEA ALP
`
`TAIRA Re Be BASAC BA ERB, CEN IDB eS AS Be BhA Yd 9HE ASAe BE
`
`SASTARE, REEAEEBBABERER AS ACH A. ARAL
`
`FA 222 SREP Yt FB] EA BAA AY BE SRSS FL Eo
`
`