CA2002643A1 - Antioxidant-free epinephrine solution for ophthalmic use - Google Patents
Antioxidant-free epinephrine solution for ophthalmic useInfo
- Publication number
- CA2002643A1 CA2002643A1 CA 2002643 CA2002643A CA2002643A1 CA 2002643 A1 CA2002643 A1 CA 2002643A1 CA 2002643 CA2002643 CA 2002643 CA 2002643 A CA2002643 A CA 2002643A CA 2002643 A1 CA2002643 A1 CA 2002643A1
- Authority
- CA
- Canada
- Prior art keywords
- solution
- epinephrine
- amount
- accordance
- hydrochloric acid
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 title claims abstract description 36
- 229930182837 (R)-adrenaline Natural products 0.000 title claims abstract description 35
- 229960005139 epinephrine Drugs 0.000 title claims abstract description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 13
- 239000003708 ampul Substances 0.000 claims abstract description 9
- 208000002177 Cataract Diseases 0.000 claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract 14
- 239000011780 sodium chloride Substances 0.000 claims abstract 7
- 238000001356 surgical procedure Methods 0.000 claims abstract 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract 7
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims abstract 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract 4
- 229910001873 dinitrogen Inorganic materials 0.000 claims abstract 4
- 230000003385 bacteriostatic effect Effects 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims abstract 2
- 239000001509 sodium citrate Substances 0.000 claims abstract 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims abstract 2
- 239000000243 solution Substances 0.000 claims 31
- 229960005419 nitrogen Drugs 0.000 claims 3
- 239000003963 antioxidant agent Substances 0.000 claims 2
- 230000003078 antioxidant effect Effects 0.000 claims 2
- 229940083608 sodium hydroxide Drugs 0.000 claims 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims 2
- 239000008223 sterile water Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract 1
- 150000002500 ions Chemical class 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 description 1
- 241000283014 Dama Species 0.000 description 1
- 101100284769 Drosophila melanogaster hemo gene Proteins 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 240000002989 Euphorbia neriifolia Species 0.000 description 1
- 241001482237 Pica Species 0.000 description 1
- 241000893638 Taractes Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- JNSGIVNNHKGGRU-JYRVWZFOSA-N diethoxyphosphinothioyl (2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetate Chemical compound CCOP(=S)(OCC)OC(=O)C(=N/OC)\C1=CSC(N)=N1 JNSGIVNNHKGGRU-JYRVWZFOSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001886 ion microscopy Methods 0.000 description 1
- 101150080264 nit2 gene Proteins 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
An epinephrine-containing solution useful in cata-ract surgery in provided by a sulfite or antioxidant-free epinephrine solution. Before use, the sulfite or antioxidant-free epinephrine solution is contained in an ampule or similar airtight container under a blanket of oxygen-free nitrogen gas. Suitable sulfite or anti-oxidant-free epinephrine solution include a sterile, aqueous epinephrine solution wherein each mL thereof contains epinephrine in the amount 1.0 mg, hydrochloric acid in the amount 0.0005 mL and sodium chloride in the amount about 9.0 mg to render said solution substantial-ly isotonic, the solution having been adjusted to a pH
of 7.0 ? 0.1 with sodium citrate and/or citric acid.
Another useful epinephrine solution contains per mL
epinephrine in the amount 1.0 mg, hydrochloric acid in the amount 0.0005 mL, sodium chloride in the amount about 9.0 mg, the pH of said solution having been ad-justed to a value in the range 2.2-5.0 with sodium hydroxide and/or hydrochloric acid. Still another useful epinephrine-containing solution has the composi-tion per mL epinephrine in the amount 1.0 mg, hydrochloro-ric acid in the amount 0.0005 mL, the remainder being sterile or bacteriostatic water, the pH of said solution having been adjusted to a value in the range 2.2-5.0 with sodium hydroxide and/or hydrochloric acid.
An epinephrine-containing solution useful in cata-ract surgery in provided by a sulfite or antioxidant-free epinephrine solution. Before use, the sulfite or antioxidant-free epinephrine solution is contained in an ampule or similar airtight container under a blanket of oxygen-free nitrogen gas. Suitable sulfite or anti-oxidant-free epinephrine solution include a sterile, aqueous epinephrine solution wherein each mL thereof contains epinephrine in the amount 1.0 mg, hydrochloric acid in the amount 0.0005 mL and sodium chloride in the amount about 9.0 mg to render said solution substantial-ly isotonic, the solution having been adjusted to a pH
of 7.0 ? 0.1 with sodium citrate and/or citric acid.
Another useful epinephrine solution contains per mL
epinephrine in the amount 1.0 mg, hydrochloric acid in the amount 0.0005 mL, sodium chloride in the amount about 9.0 mg, the pH of said solution having been ad-justed to a value in the range 2.2-5.0 with sodium hydroxide and/or hydrochloric acid. Still another useful epinephrine-containing solution has the composi-tion per mL epinephrine in the amount 1.0 mg, hydrochloro-ric acid in the amount 0.0005 mL, the remainder being sterile or bacteriostatic water, the pH of said solution having been adjusted to a value in the range 2.2-5.0 with sodium hydroxide and/or hydrochloric acid.
Description
`` ~ Z~Z~
Pl~XRINE
Thi~ lnvRntlon r~ t~ epipneph~ine ~ompo~ltlon~
o~ ~olu~lon~ ~or ophth~lmlc purpo~. For example, the intr~camQxal us~ o~ ~pinephrine, dlluted o~ u~dilut~d, in th~ tnte~lor chamber ~a~ beon recomman~d ~or the control o~ interior Yeg~n~ ~ie~ding o~ lnad~quat~ pupillary dlla~tion ln rou~in~ round pupll cataract extrnctlon and ph~coamul~PIca~n. How~r, ~h~re ~re hazard~ in~ol~a~
in the U$2 0~ in~rAo~ular ep~naphrlne #olutlon~ ln ~t~-r~ct ~urger~. ~or ~xampl~, aee the work r~portad in the pap~ by ~. O. ~chwartz et al ent~tled "Hazards o~ ~ntra-ocular Irri~a~lng Solution~ '~n~ P~Q~h~ c~taract S~r~e~y", publl~hed ln Curr~nt::co~ t~ _~n _ ~a~act Surqary, ~leG~ed Proceedin~ o~ th~_5th Bl~nnlal ~ata-, S~. ~ouis, Mo., ~. V~ Mosby Co.
(19~5), pp. 26~-~76, ~horeln lt is r~por~ed that commer-cial ~pinephrin~ in a 1:1,000 concent~tion wa3 cl3~rly d~ma~ing t~ corne~l ~ndothellum. ;Accordlng ~ ~hi~
~rti~l~ lt wa~ ~oun~ that sodlum bi~ul ite p~ese~vative u~ed in con~n~ra~on~ pre~en~ in oo~m~rcial epinbph~in~
~olutlons dama~d th~ c~rn~l en~othellum. Such da~age, how~r, co~l:d ~ pr~van~ed ir commerclal e~in~ph~ne i~
dlluted at least ~vo ti~.~s, i.e. a conoHntrat~on no~ ~o exceed 1:5,000. Fur~h~r, ac~ording ~o this ar~icl~, a relati~ely no~mal endothalial truct~r~ c~n b~ o~served:
~ ~ on ~anni~g and t~an6m~s~ion microscopy ~hen th~ n~
i~ ~XpOs~d ~o dilute eplnephrlne or 1:1,000 conc~n~r~-tlon o~ ~plnephrlne wi~hout a p~e~rvative which, ~ccord ing to tha 4rticle, d~onstrateo ths ~fect o~ diluting th~ pre~erYati~e~ ra~her tha~ d~lut~nq ~he epln~phrlne it~
.
, .
:
~%~43 - -2~
Commercially a~a~lable ~pinephrlne in~eo~lon solu-tiosl~ O~ 000 t l mg~m~) ar~ ~vallA~le ~O~ ophthalm~c purposes ~ut, ~9 ln~ic~d, mU8~ 4e ~lluted tQ 1:5~000 (0.2 mq~L) .or l:lO,OOo (0. ~. mg/mL) due eo the low pH o~
~uch ~p~n~ph~n~ lnj~c~ion solution~ ~3.0-4.0) and ~he pre~an~e the~e~n o~ sodium blsul~lte. The concentratlon o~ s~dium ~lsul~lt~ ~0.5-2.0 ~/m~ comm~roial ~pl-nephrin~ ~olu~lon~ h~l been ~ound to ~ toxic ~o the oorn~l endoth~lium and at a p~ o~ 4.0 has produced corn~al ~de~a ln the cornea O~ al~lno r~b~lt~.
~ cord~r,qly, lt is ~n ob~ect o~ t~ls lnventlon to p~o~de epin~ph~lne solutions or eplnephrin~ ln~Qct~ons whic~ can b~ ~a~Qly employed ln ophthalmlc p~oa~dura~, suc~ ~ ln cataxact extractions.
It 18 another objact o~ ~i9 lnvention to provld~
epln~phrine solu~ions whi~h do no~ cau~ corn4al damag0 or a~ toxic to the corneal endothQlium~
~ yet ~noth~r objectlon o~ thl~ inven~lon to provld~ ~Able epinephrine injRc~lon~ or ~plnephrine -solu~on~ &ult~la for ophthalmic u~e.
H~w the~ ~nd oth~ ob~e~ts of ~hi~ l~v~n~ion ~r~
~chieved ~ill b~o~e apparen~ in ~he llght o~ th~ accom-p~ny~hg di~clo~ur~ In ~t l~a~ one embodlm~n~ ~ th~
p~a:~tlce~ oP ~ lnv~ntio~ at l~ast one o~ th~ ~oregolng o~j~c~s w~ll b~ achie~ad.
~ plne~h~lne lnj~ct~on~ or epinephrin~ ~olut~ons, p~rticularly ~uit~bl~ ~or opht~al~i~ u~e, cuch as ln ca~a~ac~ operatlons, hav2 be~n pr~pared whlc~ ar~ r~se o~
, 2~ 3 . ~
a pres~rv~tl~ or antLoxidan~, ~uch as a b1qUl~it~ ~.g.
so~ium bi~ul~1te. Su~h epinephrlne solutlon~ provide improvad ~pinephrlna compo~itlons ~or ~s~ by surgeon~ a~
l~rtg~ting ~olutionq to m~int~ln hemo~ ls ~or extr~
aap~ular ca~a~ac~ ex~rac~on ~nd phaco~mul~ia~tlon. ~n co~tr~st wlth co~m~rciall~ ~Yallabl~ ~plnephrine in~ec-tion~ or ~olution~ h~vlng ~he conc~ntration of eplneph-~ina of l S l , OOO ~ 1 mg/m~), which solu~lon~ beçAuse o~ th~
pr~s~nc~ o~ sQdium bi~ul~ite t~erein a~ a pre~rv~tlve or ~ntixodxlant and ~cau~e o~ low pH (3.0-~.0~, must dilut~d prior to u~e ~o an ~pin~ph~ine content o~
l:~,OO~ (O.l mg/mL~ or to An Gpin~phr~n~ conc~n~rat~on o~
l:lO,ooO tO.l ~g/mL), th~ eplnephrino ~olutlon~ ~n accor~
dan~e with this invantion sinca ~uoh solutlon~ ar~ pre-~rv~lv~ or antlox1dAnt-~ree,..i.~. d~.~4t.!.contain a ~ulfita, quch a~ sodium b~ul~it~ c~n;Abo~:u~ed..directly, a~ a ~tr~ng~h o~ l:l,OOO tl mg~mL) or, lf de~lred, dilu~-~d ~or ophthal~ic us~. Moreov~r, 1~ d~ired, th~ c~mpo-s1~ion~ in accordanc~ wlth thi~ ln~nti on can b~ ad~u~t2d ~o d~ d pH, such ~ a p~ o~ 7.0 l or a~ a pH in thQ
~a~ge 2.~-~Ø Da~irabl~ p~cial epl~ephrln~ compo-~it~ons or solution~ ln accord~nce:with thl~ l~v~ntlon are m~int~i~ed, prior t~ u~e, in an airtight or ~eaLed a~pul~ or ~on~alner whereln ~h~ epinaph~ine 801ution ~ontaln~ there~n i~ malnt~in~d und~r a blan~t of an oxyq~n-~ree g~8 or a~mospha~e, ~uch ~ ~n ~xygen~Pr~
nitrGgan g218~
T~e ~ollowlnq are 3x~pIeD o~ compo~i~lons in accor-dance ~lth ~hl~ in~ntlon~
20~ L3 An ~pinephr~n~ solution ln ac~or~ance with thl~ lnvsntlon ~a~ prapared without Any ~ul git~ or ~ntloxidant or pre-tl~re ~gont ther~in and ampule~ or ~ontalne~ the~e-oP ~ale~ under a ni~rog~n at~no~phere. The golut1 on was mada i80tonl~ by th~ addltiorl o~ ~odl~ ~hlo~ido 60 ~ to pro~lde a sod~um chloride concen~ratlon ln ~ solut~ or o~ 9 mg~mL to ma.ke th~ solution i~tonic. Tha pH of th~
~olution wa~ al~o adju~d to a valu~ o~ 7 . O + 1 by ~che addi~ion of ~od~um ~i~rat~ and~or cltrl ~ . A suit-~bl~ ~uch aompo~i~lon per 1~l1 wou~d contain:
Epinephrine - 1. 0 mg Hydrochloxi~ a~id (12N) - o. 0005 sn$.
Sad~um chlorid~ g~o mg Sterile wat~ romalnder AmpUle8 0~ con~in~a o~ such solutions, a.g. 1, 5 and 10 mL the~e~, would ba ~ d and sa~led under el nit~os~n a,~mo6p~era .
.,. , Othe~ ep~ n~ph~ln~ ~olutior.~ in ac~rdanço wi~h thl~
lnv~nt:l~r) would ~hav~ the foll~wing~ compo~ltion per mL:
Epin~p~f n~ mg Hy~lroc}lloric ~cld (l~N) - O . 0005 mL
So~ium ~hlorlde ~ ~ . o mg Ster~l~ wat~r ~ m~ ~ nà~r Su~h ~olution~ would l~awi~e ~ filled in ~ g~ tigh~
~onta~nor under ~ nit2~0gen a~mosphe~a, t~ G pH o~ the ~olution haYlng be~n ad ju~t~d ~:o a p~l ln th~ ra~n~ 2 . 2-2~ 43 ..
S . o wl t~ sodium hydroxid* and/or hydrochlorlc aci~ .
Anoth~r example o~ ~n eplnephrin~ compo3ition in accor-dan~ wlt~ thi~ lnventlon wo~ld contaln, par m~.
Epin~phrlne - l. O m~
~yd~ochloric a~id (12N) - O. 0005 sn~
Wat~r - remainder Such solut~ons ~ould 1~XQWiS~ b~ ~illed in a g~ tight or airtigh~ contslner or ampule undor a ni~rog~n a~cmosphere, th~ pH h~ving ~e~n ad~u~ted to ~ ~alue ln tt~e rang~ 2 . O^
5 . O by ~he addition o~ ~oc~ um hydroxld~ and~or ~ydro-chlori~ ~ld.
~ 3 will b~ apparent to tho~ killed ln th~ art ln th~ llght of ~ or~go~ng di~ ;:losure, many modirlc~-tlon~ sration~ and eub~t~ tu~cion~ a~e po~6i~1~ in the prhctlce of hi~ ventlon witho~t dep~rting ~rom t~o ~pi~it ~r 5COp~! thor~o~
-:
.
,, , ~
., ;
Pl~XRINE
Thi~ lnvRntlon r~ t~ epipneph~ine ~ompo~ltlon~
o~ ~olu~lon~ ~or ophth~lmlc purpo~. For example, the intr~camQxal us~ o~ ~pinephrine, dlluted o~ u~dilut~d, in th~ tnte~lor chamber ~a~ beon recomman~d ~or the control o~ interior Yeg~n~ ~ie~ding o~ lnad~quat~ pupillary dlla~tion ln rou~in~ round pupll cataract extrnctlon and ph~coamul~PIca~n. How~r, ~h~re ~re hazard~ in~ol~a~
in the U$2 0~ in~rAo~ular ep~naphrlne #olutlon~ ln ~t~-r~ct ~urger~. ~or ~xampl~, aee the work r~portad in the pap~ by ~. O. ~chwartz et al ent~tled "Hazards o~ ~ntra-ocular Irri~a~lng Solution~ '~n~ P~Q~h~ c~taract S~r~e~y", publl~hed ln Curr~nt::co~ t~ _~n _ ~a~act Surqary, ~leG~ed Proceedin~ o~ th~_5th Bl~nnlal ~ata-, S~. ~ouis, Mo., ~. V~ Mosby Co.
(19~5), pp. 26~-~76, ~horeln lt is r~por~ed that commer-cial ~pinephrin~ in a 1:1,000 concent~tion wa3 cl3~rly d~ma~ing t~ corne~l ~ndothellum. ;Accordlng ~ ~hi~
~rti~l~ lt wa~ ~oun~ that sodlum bi~ul ite p~ese~vative u~ed in con~n~ra~on~ pre~en~ in oo~m~rcial epinbph~in~
~olutlons dama~d th~ c~rn~l en~othellum. Such da~age, how~r, co~l:d ~ pr~van~ed ir commerclal e~in~ph~ne i~
dlluted at least ~vo ti~.~s, i.e. a conoHntrat~on no~ ~o exceed 1:5,000. Fur~h~r, ac~ording ~o this ar~icl~, a relati~ely no~mal endothalial truct~r~ c~n b~ o~served:
~ ~ on ~anni~g and t~an6m~s~ion microscopy ~hen th~ n~
i~ ~XpOs~d ~o dilute eplnephrlne or 1:1,000 conc~n~r~-tlon o~ ~plnephrlne wi~hout a p~e~rvative which, ~ccord ing to tha 4rticle, d~onstrateo ths ~fect o~ diluting th~ pre~erYati~e~ ra~her tha~ d~lut~nq ~he epln~phrlne it~
.
, .
:
~%~43 - -2~
Commercially a~a~lable ~pinephrlne in~eo~lon solu-tiosl~ O~ 000 t l mg~m~) ar~ ~vallA~le ~O~ ophthalm~c purposes ~ut, ~9 ln~ic~d, mU8~ 4e ~lluted tQ 1:5~000 (0.2 mq~L) .or l:lO,OOo (0. ~. mg/mL) due eo the low pH o~
~uch ~p~n~ph~n~ lnj~c~ion solution~ ~3.0-4.0) and ~he pre~an~e the~e~n o~ sodium blsul~lte. The concentratlon o~ s~dium ~lsul~lt~ ~0.5-2.0 ~/m~ comm~roial ~pl-nephrin~ ~olu~lon~ h~l been ~ound to ~ toxic ~o the oorn~l endoth~lium and at a p~ o~ 4.0 has produced corn~al ~de~a ln the cornea O~ al~lno r~b~lt~.
~ cord~r,qly, lt is ~n ob~ect o~ t~ls lnventlon to p~o~de epin~ph~lne solutions or eplnephrin~ ln~Qct~ons whic~ can b~ ~a~Qly employed ln ophthalmlc p~oa~dura~, suc~ ~ ln cataxact extractions.
It 18 another objact o~ ~i9 lnvention to provld~
epln~phrine solu~ions whi~h do no~ cau~ corn4al damag0 or a~ toxic to the corneal endothQlium~
~ yet ~noth~r objectlon o~ thl~ inven~lon to provld~ ~Able epinephrine injRc~lon~ or ~plnephrine -solu~on~ &ult~la for ophthalmic u~e.
H~w the~ ~nd oth~ ob~e~ts of ~hi~ l~v~n~ion ~r~
~chieved ~ill b~o~e apparen~ in ~he llght o~ th~ accom-p~ny~hg di~clo~ur~ In ~t l~a~ one embodlm~n~ ~ th~
p~a:~tlce~ oP ~ lnv~ntio~ at l~ast one o~ th~ ~oregolng o~j~c~s w~ll b~ achie~ad.
~ plne~h~lne lnj~ct~on~ or epinephrin~ ~olut~ons, p~rticularly ~uit~bl~ ~or opht~al~i~ u~e, cuch as ln ca~a~ac~ operatlons, hav2 be~n pr~pared whlc~ ar~ r~se o~
, 2~ 3 . ~
a pres~rv~tl~ or antLoxidan~, ~uch as a b1qUl~it~ ~.g.
so~ium bi~ul~1te. Su~h epinephrlne solutlon~ provide improvad ~pinephrlna compo~itlons ~or ~s~ by surgeon~ a~
l~rtg~ting ~olutionq to m~int~ln hemo~ ls ~or extr~
aap~ular ca~a~ac~ ex~rac~on ~nd phaco~mul~ia~tlon. ~n co~tr~st wlth co~m~rciall~ ~Yallabl~ ~plnephrine in~ec-tion~ or ~olution~ h~vlng ~he conc~ntration of eplneph-~ina of l S l , OOO ~ 1 mg/m~), which solu~lon~ beçAuse o~ th~
pr~s~nc~ o~ sQdium bi~ul~ite t~erein a~ a pre~rv~tlve or ~ntixodxlant and ~cau~e o~ low pH (3.0-~.0~, must dilut~d prior to u~e ~o an ~pin~ph~ine content o~
l:~,OO~ (O.l mg/mL~ or to An Gpin~phr~n~ conc~n~rat~on o~
l:lO,ooO tO.l ~g/mL), th~ eplnephrino ~olutlon~ ~n accor~
dan~e with this invantion sinca ~uoh solutlon~ ar~ pre-~rv~lv~ or antlox1dAnt-~ree,..i.~. d~.~4t.!.contain a ~ulfita, quch a~ sodium b~ul~it~ c~n;Abo~:u~ed..directly, a~ a ~tr~ng~h o~ l:l,OOO tl mg~mL) or, lf de~lred, dilu~-~d ~or ophthal~ic us~. Moreov~r, 1~ d~ired, th~ c~mpo-s1~ion~ in accordanc~ wlth thi~ ln~nti on can b~ ad~u~t2d ~o d~ d pH, such ~ a p~ o~ 7.0 l or a~ a pH in thQ
~a~ge 2.~-~Ø Da~irabl~ p~cial epl~ephrln~ compo-~it~ons or solution~ ln accord~nce:with thl~ l~v~ntlon are m~int~i~ed, prior t~ u~e, in an airtight or ~eaLed a~pul~ or ~on~alner whereln ~h~ epinaph~ine 801ution ~ontaln~ there~n i~ malnt~in~d und~r a blan~t of an oxyq~n-~ree g~8 or a~mospha~e, ~uch ~ ~n ~xygen~Pr~
nitrGgan g218~
T~e ~ollowlnq are 3x~pIeD o~ compo~i~lons in accor-dance ~lth ~hl~ in~ntlon~
20~ L3 An ~pinephr~n~ solution ln ac~or~ance with thl~ lnvsntlon ~a~ prapared without Any ~ul git~ or ~ntloxidant or pre-tl~re ~gont ther~in and ampule~ or ~ontalne~ the~e-oP ~ale~ under a ni~rog~n at~no~phere. The golut1 on was mada i80tonl~ by th~ addltiorl o~ ~odl~ ~hlo~ido 60 ~ to pro~lde a sod~um chloride concen~ratlon ln ~ solut~ or o~ 9 mg~mL to ma.ke th~ solution i~tonic. Tha pH of th~
~olution wa~ al~o adju~d to a valu~ o~ 7 . O + 1 by ~che addi~ion of ~od~um ~i~rat~ and~or cltrl ~ . A suit-~bl~ ~uch aompo~i~lon per 1~l1 wou~d contain:
Epinephrine - 1. 0 mg Hydrochloxi~ a~id (12N) - o. 0005 sn$.
Sad~um chlorid~ g~o mg Sterile wat~ romalnder AmpUle8 0~ con~in~a o~ such solutions, a.g. 1, 5 and 10 mL the~e~, would ba ~ d and sa~led under el nit~os~n a,~mo6p~era .
.,. , Othe~ ep~ n~ph~ln~ ~olutior.~ in ac~rdanço wi~h thl~
lnv~nt:l~r) would ~hav~ the foll~wing~ compo~ltion per mL:
Epin~p~f n~ mg Hy~lroc}lloric ~cld (l~N) - O . 0005 mL
So~ium ~hlorlde ~ ~ . o mg Ster~l~ wat~r ~ m~ ~ nà~r Su~h ~olution~ would l~awi~e ~ filled in ~ g~ tigh~
~onta~nor under ~ nit2~0gen a~mosphe~a, t~ G pH o~ the ~olution haYlng be~n ad ju~t~d ~:o a p~l ln th~ ra~n~ 2 . 2-2~ 43 ..
S . o wl t~ sodium hydroxid* and/or hydrochlorlc aci~ .
Anoth~r example o~ ~n eplnephrin~ compo3ition in accor-dan~ wlt~ thi~ lnventlon wo~ld contaln, par m~.
Epin~phrlne - l. O m~
~yd~ochloric a~id (12N) - O. 0005 sn~
Wat~r - remainder Such solut~ons ~ould 1~XQWiS~ b~ ~illed in a g~ tight or airtigh~ contslner or ampule undor a ni~rog~n a~cmosphere, th~ pH h~ving ~e~n ad~u~ted to ~ ~alue ln tt~e rang~ 2 . O^
5 . O by ~he addition o~ ~oc~ um hydroxld~ and~or ~ydro-chlori~ ~ld.
~ 3 will b~ apparent to tho~ killed ln th~ art ln th~ llght of ~ or~go~ng di~ ;:losure, many modirlc~-tlon~ sration~ and eub~t~ tu~cion~ a~e po~6i~1~ in the prhctlce of hi~ ventlon witho~t dep~rting ~rom t~o ~pi~it ~r 5COp~! thor~o~
-:
.
,, , ~
., ;
Claims (15)
1. A aqueous sulfite or antioxidant-free epineph-rine solution suitable for ophthalmic use com-prising epinephrine, hydrochloric acid, sodium chloride and sterile or bacteriostatic water, the resulting solution having a pH of 7.0 ? 0.1 adjusted with sodium citrate and/or citric acid, the amount of sodium chloride present in said solution being adjusted so that said solution is substantially isotonic.
2. An airtight ampule or container containing a solution in accordance with Claim 1, said solu-tion being contained within said ampule or container under a blanket of oxygen-free nitro-gen gas.
3. A solution in accordance with Claim 1 wherein each mL of said solution contains epinephrine in the amount 1.0 mg, hydrochloric acid in the amount 0.0005 mL, sodium chloride in the amount about 9.0 mg, the remainder being water.
4. A aqueous sulfite or antioxidant free epineph-rine solution suitable for ophthalmic use com-prising epinephrine, hydrochloric acid, sodium chloride and sterile or bacteriostatic water, the pH of the resulting epinephrine solution being adjusted to 2.20-5.0 with sodium hydrox-ide and/or hydrochloric acid.
5. An airtight ampule or container containing a solution in accordance with Claim 4, said solu-tion being contained within said ampule or container under a blanket of oxygen-free nitro-gen gas.
6. A solution in accordance with Claim 4 wherein each mL of said solution contains epinephrine in the amount 1.0 mg, hydrochloric acid in the amount 0.0005 mL, sodium chloride in the amount about 9.0 mg, the remainder being water.
7. A sulfite or antioxidant free epinephrine solu-tion suitable for ophthalmic use comprising epinephrine, hydrochloric acid and sterile water, the resulting solution having a pH ad-justed to a value in the range 2.2-5.0 with sodium hydroxide and/or hydrochloric acid.
8. An airtight ampule or airtight container con-taining a solution in accordance with Claim 7, said solution being contained within said ampule or container under a blanket of oxygen- free nitrogen gas.
9. A solution in accordance with Claim 7 wherein each mL of said composition contains epinephrine in the amount 1.0 mg, hydrochloric acid in the amount 0.005 mL, the remainder being water.
10. In human cataract surgery wherein an epineph-rine-containing solution is applied to the eye, the improvement which comprises employing an epinephrine solution in accordance with Claim 1.
11. In human cataract surgery wherein an epineph-rine-containing solution is applied to the eye, the improvement which comprises employing an epinephrine solution in accordance with Claim 3.
12. In human cataract surgery wherein an epineph-rine-containing solution is applied to the eye, the improvement which comprises employing an epinephrine solution in accordance with Claim 4.
13. In human cataract surgery wherein an epineph-rine-containing solution is applied to the eye, the improvement which comprises employing an epinephrine solution in accordance with Claim 6.
14. In human cataract surgery wherein an epineph-rine-containing solution is applied to the eye, the improvement which comprises employing an epinephrine solution in accordance with Claim 7.
15. In human cataract surgery wherein an epineph-rine-containing solution is applied to the eye, the improvement which comprises employing an epinephrine solution in accordance with Claim 9.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26906388A | 1988-11-09 | 1988-11-09 | |
| US269,063 | 1988-11-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2002643A1 true CA2002643A1 (en) | 1990-05-09 |
Family
ID=23025641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2002643 Abandoned CA2002643A1 (en) | 1988-11-09 | 1989-11-09 | Antioxidant-free epinephrine solution for ophthalmic use |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2002643A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2001833A1 (en) * | 2006-03-24 | 2008-12-17 | National Research Council of Canada | Anti-diabetic cataract compounds and their uses |
| US9283197B1 (en) * | 2014-08-15 | 2016-03-15 | Jugal K. Taneja | More potent and less toxic formulations of epinephrine and methods of medical use |
| US10004700B1 (en) * | 2017-05-16 | 2018-06-26 | Jugal K. Taneja | More potent and less toxic formulations of epinephrine and methods of medical use |
| US10285957B2 (en) | 2016-08-25 | 2019-05-14 | Imprimis Pharmaceuticals, Inc. | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof |
| US10993921B2 (en) * | 2013-10-03 | 2021-05-04 | Harrow Ip, Llc | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof |
| US11266611B2 (en) | 2017-05-16 | 2022-03-08 | Eton Pharmaceuticals, Inc. | More potent and less toxic formulations of epinephrine and methods of medical use |
-
1989
- 1989-11-09 CA CA 2002643 patent/CA2002643A1/en not_active Abandoned
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2001833A1 (en) * | 2006-03-24 | 2008-12-17 | National Research Council of Canada | Anti-diabetic cataract compounds and their uses |
| EP2001833A4 (en) * | 2006-03-24 | 2011-03-02 | Ca Nat Research Council | ANTIDIABETIC CATARACT COMPOUNDS AND THEIR APPLICATION |
| US10993921B2 (en) * | 2013-10-03 | 2021-05-04 | Harrow Ip, Llc | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof |
| US11045432B2 (en) | 2013-10-03 | 2021-06-29 | Harrow Ip, Llc | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof |
| US9283197B1 (en) * | 2014-08-15 | 2016-03-15 | Jugal K. Taneja | More potent and less toxic formulations of epinephrine and methods of medical use |
| US10285957B2 (en) | 2016-08-25 | 2019-05-14 | Imprimis Pharmaceuticals, Inc. | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof |
| US10004700B1 (en) * | 2017-05-16 | 2018-06-26 | Jugal K. Taneja | More potent and less toxic formulations of epinephrine and methods of medical use |
| US11266611B2 (en) | 2017-05-16 | 2022-03-08 | Eton Pharmaceuticals, Inc. | More potent and less toxic formulations of epinephrine and methods of medical use |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR0160443B1 (en) | Aqueous ophthalmic solutions and method for preserving the same | |
| EP0700249B1 (en) | Anti-infective agents | |
| DE69108469T2 (en) | Antiviral glove. | |
| US4550022A (en) | Tissue irrigating solution | |
| US4443432A (en) | Ophthmalic irrigating solution | |
| US5880107A (en) | Sodium hyaluronate based ophthalmic formulation for use in eye surgery | |
| US5487896A (en) | Antimicrobial glove comprising a rapid release matrix system for antiinfective agent delivery | |
| DE69333011T2 (en) | OXIDIZER AND POLYVINYLPYRROLIDONE CONTAINING DISINFECTANT SOLUTION FOR CONTACT LENSES | |
| CA2002643A1 (en) | Antioxidant-free epinephrine solution for ophthalmic use | |
| DE602004008651T2 (en) | LIQUID PREPARATION FOR CONTACT LENSES | |
| HU225329B1 (en) | Use of zinc or cobalt hyaluronate associate for the manufacture of pharmaceutical compositions of antimicrobial activity | |
| CN117137866A (en) | Ophthalmic compositions containing diquafos and cationic polymers | |
| DE2918799A1 (en) | OPHTHALMIC SOLUTION | |
| DE1667942A1 (en) | Device for storing and preserving objects made from swollen hydrogels, in particular contact lenses | |
| DE2658237C3 (en) | Use of cysteine or N-acetylcysteine | |
| US4837021A (en) | Two part tissue irrigating solution | |
| DE851240C (en) | Device for aseptic tooth and wound treatment | |
| YORK et al. | Polyvinylpyrrolidone iodine: corneal toxicology and epithelial healing in a rabbit model | |
| HARRIS et al. | In-office microwave disinfection of soft contact lenses | |
| GB2100599A (en) | Pharmaceutical preparation for treating glaucoma and ocular hypertension | |
| DE10000612A1 (en) | Aqueous active substance preparations, especially eye drops, nasal drops and nasal sprays, contain sodium chloride in place of preservatives | |
| Mørk | Polyvinylpyrrolidone‐iodine as a disinfectant in eye surgery for five years | |
| EP1522321B1 (en) | Method for disinfecting and/or cleaning contact lenses, using a liquid aqueous composition comprising at least one constituent of the aloe vera plant | |
| DE69320332T2 (en) | ANTIVIRAL CONDOMS | |
| DE19834087C1 (en) | Aqueous preservative solution for storage of animal tissue, especially porcine heart valves, contains sodium, potassium, magnesium and calcium salts, glucose and chelate former |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |