CA1053578A - Sterilizing an article with iodophor containing aldehydic reducing agent - Google Patents

Abstract

A B S T R A C T

A method of sterilizing an article comprises contacting the article with an aqueous solution of an iodophor also containing sufficient of an organic aldehydic reducing agent to reduce the available iodine level of the solution to substantially zero within a period of from 30 minutes to eight hours preferably from 1 to 4 hours; the reaction products of the iodophor and the reducing agent being non-toxic and non-irritant. The method of the invention may be applied to articles formed of hydrophilic polymer, e.g. contact lenses, in which cases the iodophor is preferably a complex of iodine with a hydrophilic polymer or a nonionic surface active agent and the reducing agent is formic acid or an alkali metal salt thereof.

Description

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~053S78 This invention i~ concerned with improvements in and relating to the sterilization of articles, The use of aqueous solutions cont.aining available iodine for steriliz.in.g articles is well established. Cornmonly, xuch sterilization is effected by contacting the article to be sterili.~ed with the sterilizing solution, often by immersing the article thereinc After removing the articlefrorn contact with the sterilizing solution it is often desirable to remove, for example by rinsing with water~
any adherent sterilizing solution from the article, particularly when the article is to be brought into contact, directly or indirectly with human tissue, ~-.

It has now been found, in accordance with the present invention, that it is not necessary to remove any adherent sterilizing solution provided that the steri.lizing solution with whlch the article to be sterilized is brought into contact also contains a reducing agent capable of reducing the available iodine level of the sterilizing solution to substantially zero (with the production of non-toxic and non-irritant reaction products) in a period of at least 30 minutes, Thus it has been found tllat the sterilizing capacity or effectiveness of a sterilizing solution containing available iodine as sterilizin~ agent is not adversely impaired by the presellce of a reducing agent for reducing the level of available iodine provided -- 1 -- , ,. .

that the reducillg agen~t does not react with the iodine too last, i.e. doe5 not reduce the available iodine level to substarltially zero in less than 30 minutes. ~he reducing agent shou]d be present in an amount to reduce substantially all of the a~ailable iodine and pre~erably the reducing agent and amoun-t thereof should be such that substantially all o~
the avai]able iodine is reduced within a perio~ of not more than eight hours.

Accordingly, the present invention provides a method of sterilizing an article which comprises contacting the article with an aqueous solution of an iodophor also contain-ing sufficient of an organic aldehydic reducing agent to reduce the available iodine level of the solution to substan-tially zero within a period of from 30 minutes to eight hours;
the reaction products of the iodophor and the reducing agent being non-toxic and non-irritant.

~ he term "iodophor" as used herein is intended to refer to ~ water-soluble complex of iodine with an organic complexin~ agent which complex, on SO]UtiO]l in water, yields a~-ailable (i.e.titratable) iodine. Suitable complexi~g agents include hydrophilic, water-soluble polymers such as cellulose ethers, polyvirlylpyrrolidone and polyvinyl alcohol and anionic, cation~c, nonionic ænd amphoteric surface active agents such as polyalkoxylated alkylphenols (e.g. nonylphenoxypoly (ethyleneoxy) ethanol), polyalkoxylated alkanols, long chain quarternary amines, all~yl sulphates (e.g. sodium lauryl sulphate) and alkylarylsulphonates (e.g.sodium alk~lbenzene sulphonates). A particularly preferred iodophor for use in the mcthod oL l~le inverltion is a polyvinylpyrroli~one com~lex (so-c~Lled "Povidonc Iodine", hereinafter sir~pl~
referred to as PVP/I2 complex).

~he iodophor should be present in the sterilizing solution in an amount sufficient to give a sterilizing level of available iodine beariDg in mind -the fact that the solution will also contai~ a reducing agent which will act to reduce the level of available iodine. In general, it has been fo~m d that provided the available iodine level is at least 5 ppm for a period o~ at least 15 minutes effective steril-i~ation will be achieved. Accordingly~ the iodophor will generally be present in the solution to give an initial available iodine level (i.e. the level of available iodine as determined by titration before -the addition of or reaction with the reducing agent or con~act with the article to be sterilized) o~ at least 10 ppm, pre~erably at least 20 ppm.
~he initia1 availa~le ioLine level will ordin~ril~J not nee to be above 300 ppm and is preferably from 25 to 100 ppm and most preferably is about 50 ppm.

As indicated above, the reducing agent employed in the method of the invention is an organic aldehydic reducing agent and this term is intended to refer to a cornpound cor-taining a group -CH0 or which-evolves groups containing such a grouping or dissolution in water (e.g. hexamine)~ Preferred aldehydic reducing agents for use in accordance with the invention include reducing ~arboxy1ic acids (especially ~ormic acid) alld salts (especially alkali metal salts) thereof and reducing sugars, e~g. glucose and arabinose. A particularly preferred reducing agent is sodium ~orma-te. Such reducing ageIlts reduce the available iodine -to iodide ions and in the process are themselves converte~ to non-toxic and non-irritant products~

~he initial steri]izing so]u-tion mus-t contain sufficient of -the reducing agent to reduce the available iodine level of the solution to substantiall~ zero (i.e.
an available iodine level of 1 pp~ or less, i.e. a level virtually lmdetectable by conventional analytical techniques) `
at commonly encountered ambient temperatures (e.g. 5-40C).
Accordingly the reducing agent must be present in molar excess over the available iodine. ~he actual molar excess of reducing agent will depend upon the nature of the iodophor and the ~e~ucing agent but generally it is preferred that the reducing agent be present in an at least tenfold molar amount relative to the available iodine in the iodophor, more preferably in an amount of from 10 to 800 moles per mole of avaiiable iodine, mosJG preferably in an amoun-t of from 100 to 500 moles per mole of available iodine.

As will be appreciated, in accordance with the method of the invention the article to be sterilized is immersed in the iodophor/reducing agent solution and allowed to remain immersed therein until the available iodine has been reduced to su~stantially zero (for example as indicated by the colour change of the solution from am~er to clear). ~he article may then be removed therefrom and il brought into contact, directly or indirectly, ~lith human tissue will have no uDdesira~le tcxic or irri-tant `effects. ~hus, the sterilizing method of the invention finds particular use in the sterilization of articles , :

~ 053578 which are intended to come into contac-t with h~n tissue, e.~. surgica] instruments and especially, contact lenses.
~he invention may also be applied to the sterilization of articles made of metal corrodible by thc action of available iodine. In accordance with a preferrea embodiment of the invention the sterilizing method is applied to contact lenses, especially so-called "soft" con-tac-t lenses or other articles made of similar hydrophilic polymers.

It is the common prac-tice to store contact lenses made of h~Jdrophobic polymers such as polymethylme-thacrylate (so-called "hard lenses"), in water or saline when the lenses are not in use since5 if they are not so stored, the lenses tend to undergo sligh-t contrac-tion or deformation since the polymers of which they are formed are not wholly h~drophobic and absorb small quantities of water. In the case of so-called "soft" contact lenses, i.e. those formed of hydrophilic ool.ymers ~ f~ ely lightly ~;rossi.i.:~lk~d ~oly~ne~ orr copo?y~ners of hydrophilic monomers such as hydroxyalkyl acrylates or methacrylates (eOg. hydroxyethyl methacrylate) or vinyl pyrrolidone, storage of the lens in water or saline when not in use is mandatory since such polymers when in use contain

2~/o or more of water (i.e. are in the form of "hydrogels") ~nd hence undergo considerable deformation on drying and if allowed to dry out coinpletely become unacceptably brittle.
It is most desirable that some degree of sterilization be effected whilst the lens is stored in the appropriate liquid in order that the lens ma-~ be maintained in an accepta~bly sterile condition for use. ~his may, in some cases, be 1053S~8 achievcd by heat sterilization of -the liquid containing -the lens but this is often unadvisable since some of the polymers are heat-sensitive, especially at sterllization temperatures.
Accordin~ly, in the case o~ the "hard" lenses it has been the practice to incorporate bactericides in the storage liquid, commonly used bac-tericides being, for example, chlorhexidine and quarternar~ germicides such as benzalkonium chloride. Solutions containin gthese bactericides however, are inappropriate for the "soft" lenses since in the case of such polymers, the bactericide has been found to become pre-ferentially concentrated within the hydrogel or polymer ma-trix. Accordingly, the lenses when removed from the storage solution can contain an unacceptably high concentratlon of bactericide which is subsequently elu-ted by the tear fluid when in position in the eye an~ may have a long or short term irritant effect.

1~)53578 The method of the invention may be applied to such "soft" contact lenses or articles made of similar hydrophilic polymers (hereinafter sirnply referred to as "lenses"), IIowever, the polymers of the lenses are, as indicated above, in the form of hydr~gels and contain substarltial amounts of water. Accordingly the lenses themselves may absorb available iodine and it is therefore necessary to reduce (by means of the reducing agent) the iodine in the lenses to substantially zero for two reasons. Firstly, the presence of available iodine in the lense may cause a short or long term 1~ irritancy effect in the wearer's eye if the iodine is not substantially removed, Secondly, the lens on absorbing iodine acquire~ a yellowish/
amber coloration and clearly the lens must be clear before being worn and hence the iodine must be substantially removed, The proble~D
is exacerbated by the fact that it appears that in many cases the a~ailable iodine may preferentially concentrate in the lens as c~p~Gsed to the sterilizing solution. In order for the reducing agent to reduce the iodine in the lens it appears that it is necessary for the reducing agent to pass from the sterilizmg solution into the water contained in the lens hydrogel since otherwise an unduly long period of time (i,e, considerably in e~cess OI eight hours) may be required to clear the lens of iodine. This is believed to be due to the fact that If the reducing agent camlot enter the lens hydrogel water it can only react with a~allable iodine at the surface of the lens and that the iodine from the body of the lens is only slowly liberated at the lens ~5 surface, Accordingly the reducing agent employed in the sterilization ., -.i ~
1~53578 of a lcns should be one capab:Le of entering the water of the lens hydrogel and not all reducing agents are apparently capable of so doing or if so are unduly irritant to the ocular tissue. Howevcr, it has ~een found that formic acid and its alkali metal ~alts (especially sodium formate) do meet the nece~sary criteria. ~rther, the iodophor (i.e.
complexing agent) should be non-irritant to ocular tissue and it has been found that iodophors derived from hydrophilic polymers ~r nonionic surface active agents are not so irritant and are thus suitable for use in the sterilization of lenses.

Another factor which comes into consideration in the sterilization o~ lenses ~ormed of hydrophilic polymers is the nature of the polymer itself. ~hus such lenses are commonly derived from hydroxyl alkyl acrylates (e.g. hydroxy-ethyl methacrylate) and/or vinyl pyrrolidone as constituentmonomers to provide the desired hydrophilic polymers. It has been found that polymers derived from mo~omers containing too great a proportion of vinyl pyrrolidone are very difficult to clear of iodine and, hence, it appears that the sterili~ing method of the present invention is generally not sui-ta~le Ior the sterilization of polymers derived from more than 35% by weight of ~inyl pyrrolidone, ùnless ot~er modifying monomers, such as methacrylic acid, are present. It will in any event be a simple matter to establish, oy simp~e test, whether any particular polymer may be satisfactorily sterilized usi~g the method of the invention.
~ he p~ of any residual liquid in contact with the soft lens should be from 5.0 to 8.0,prefera~1y 6.5 to 7.5,and hence it is desiral)lc tha~ a pll adjlJ~itcr, ~enerally a l)ufle system, such as a pllosphatc bufler systcrrl be added to the sterilization solution, to bring the pH of the final liquid to the desired level. It has also been found that adjustment of pH to this level, especially to a level of about 7.1, markedly improves the effectiveness of some reagents, It is also desirable that the tonicity of the final solution, after reaction with the reducing agent, be approximately equal to that of the eye fluids and, hence, it is also most desirable that a tonicity adjusting agent, generally sodium chloride, be added to the sterilization solution.

- The buffers are suitably present in arnounts to give from 100 to 10, 000 ppm of buffer in the sterilization solution when used in tile treat~nent of 50 ppm availablo iodine so'utions~ ~he tonicity adjusting agents should be present in the composition in an amount sufficient to render the solution approximately isotonic with human tears, When calculating the amount of sterilizing agent reagent, buffering agen~ and/or tonicity adjusting to be present in the compositions of the invention, account must be takén of the strength of the iodine or iodine complex sterilization solution produced and the amount to be treated. A 50 ppm available iodine solu~ion has been fourld to be very su.itable for sterilizing soft con~act lenses. Generally the lenses will be brought into co.ntact with the sterilization solution in a so-called "lens case" having a capacity of irorn 5 - 25 ml, preferably about 10 ml.

~he sterilizing solution used in accordance with the invention will be prepared by d.issolving the iodophor and re~ucing a~ent (and possibly tonicity adjusting agent and buffer) in water. ..

Considering only the iodophor and reducing agent the mixed solution may be prepared by:-(1) dissolving solid iodophor and solid reducing agent in the desired amount of water;
(2) mixing -together individual pre~or.me~ ~olr~ti.ons -~5 of the reducing agent and iodophor;
~3) mixing apl~eformed solution of iodGphGr with water and dissolving therein solid reducing -".
agent;
(4) mixing apreformed solution of reducing agent with water and dissolving therein solid iodophor;
(5) dissolving solid reducing a~ent in aprefo~med solution of iodophor,or (~) dissolving solid iodophor in apreformea solu~ion of reducing agent.

In all the above cases the amounts of iodophor and reducing agent and water (which may be solvent water where solutions o~ iodophor and/or reaucing agent are employed) will, of course, 'be such as to provide a final sterilizing solution having the desired initial concentration of iodophor -, ~OS~3S78 (J ( ' Il t.
~ (c~r~ gly i~ will ~e s~?n t:hat ;n methods (l), (3), (4~, (5) and (6) the iocloi~]--or and/or re(lllciny agent may L)e added as a solid and for col~venience of operation it is preferred that the solid iodopilor or redllci3lg ac~ent be formulated in solid unit dos.~ge form (e.y. a tab]et) contain;ng the appropriate amount of iodophor or reducin~ agent for addi~ion to a pre-determined amount of water (say for example about 10 ml in the case of a solution for sterilizing soft lenses in a lens case).
It will be appreciated that in some cases it is not possible to formulate iodophors in solid orm in which case methods (1), (4) and (6) will not be appropriate but solid iodophors are avail-able (e.g. the PVP/I2 complex) and thus may be used in these methods of operation. The solid unit dosage form may contain ingredients other than the iodophor or reducing agent and thus, in the case of the sterilization of soft lenses may contain buffing agents and/or tonicity adjusting agents. Further, in this latter case, the unit dosage fo~m should not contain any insoluble excipient which will give rise to solid contaminate in the sterilizing solution which will adhere to the lens and then irritate the eye. This problem may be overcome by simply using sodium chloride (a tonicity adjusting agent) as excipient.
Solid unit dosage forms for containing iodophor or reducing - ~
agent suitable for the sterilization of soft lenses in approp- ~ `
riate amounts are themselves new and are provided as a further feature of the invention.

.
. . .

~ c~ordin<~Ly the invel~ion also provi-les a solld unit doss~e for contailliny from 2 to 30 mg (preferably from 2-10 mg) of an iodophor which is a con~plex of iodine with a hydrophilic polymer or a nonionic surface active agent, the unit dosage form prelerably also containlng sodium chloride. The invention also provides a solid unit dosage form containing from 20 to 300 mg of an alkali metal formate, preferably sodium formate, the unit dosage form preferably also containing sodium chloride and/or a buffering agent.
Methods (2), (3), (4), (5) and (6) also require the use of a preformed solution of iodophor or reducing agent. In these instances it should be noted that not all iodophors (e.g.
PI~/I2 complex) gi~e stable solutions at the generally low (e.g.
50 ppm) available iodine concentrations envisaged in the practice of the invention and thus method (6) may be inappropriate and in the case of methods (2) and (3) the preferred iodophor solution may be a relatlvely concentrated solution (e.g. have a concen-tration of from 0.5 to 5% of available iodine) the bulk of the watér content of the sterilizing solution being made up by the water of the reducing agent solution (method 2) or the added water (methoa 3). :~
Of the methods outlined above, methods (2), (3), (5) and (6) are the more preferred and methods ~3? and (6) are the most preferred. A further embodiment of the invention is, , therefore, directed towards two-part packs for carrying and ~ -methods (2), (3), (5) and (6~. Thus, the invention also provides two-part packs comprising:-

3~ ~ ~

, :

3~053578 (a) an aqueolls solution of an iodophor and a:n an aqueous solution of a reducing agent;
(b) an aqueous solu-tion of an isodophor and a solid dosage unit form carrying a reducing agent; and (c) an aqueous solution of a reducing agent and a solid dosage unit form carr~ing an isodophor.
~he two-part pack (b) will be slli-table for carrying out methods (3) and (6) but in -the former case the aqueous isodophor solution will generally be a relatively concentra-ted solution (as it may be in thecase of pack (a) for carrying out method (2))whereas in -the latter case it will generally be a more dilute solution containing available iodine at the desired initial level.
~he solutions may be put up in individual containers (which may be sterilized in -the case of -the reducing agent solution) or in multidose contaiIlers (in which case a reduc-ing agent solution may also contain a preservative bacteric;~e, for e~ample one also capable of reducing available iodine, e.g. glutaraldehyde). Where the sterilizing solution is intended for the stèrilization of sof-t lenses the solution may also contain a tonicity adjusting agent; thus in the case of the iodophor solution/reducing agent solid unit dosage for~
system the buffer and tonicity adjusting agents are advantag-eously present i~ the dosage unit form whereas in the case of the reducing agent solution/icdophor solid uni-t dosage form system the buffer is advantageousl~J present in -the solution ~-~d the tonicity adjusting agent in the unit dosage form.

105357~
The dosage unit form may take any suitable form, preferably a dry solid Form. However, having regard to the requirement that the composition leaves no insoluble particulate matter in the sterilization solution either as a result of the reaction or due to excipients tsince this might irritate the eye) it is most convenient to simply tablet the ingredients without any excipient.
For sterilization of soft lenses the reducing agent solution should be sterile and, to this end, may be made up in the form of sterilized (autoclavable) or irradiated unit doses (e.g. containing about lO ml of the solution) in suitable auto-clavable containers such as bottles or plastics laminated foil sachets with low moisture vapour permeability, or in the form of a multidose composition to be contained in a suitable container and also containing a sterilizing or antibacterial agent. Such an antibacterial agent should be one which does not concentrate in soft hydrophilic polymers and most preferably is one which itself reacts with iodine to produce harmless and non-irritant products, e.g. glutaraldehyde.
In order that the invention may be well understood the following Examples are given by way of illustration only.
Example l PVP/I2 tablets for addition to lO ml sachets of sodium formate solution had the following composition.
PVP/I2 5 mg/tablet Sodium chloride 35 mg/tablet Boric acid 1.25 mg/tablet 10~3578 The PVT'/I2 and sodi~n c;hloride wcre each passed throug}l a 60 mesh sieve and then m~ ed together. Boric acid (passing -through an ~0 mesh sieve) was added to the mixt~re as lubricant. '~he mixed powders werc tabletted using 5/32 inch punches and dies.

~ he sodium formate soluticn had the following composition:-- Sodium formate 0.5 % by weight Sodi~n dihydrogen phospha-te 0~023% by weight Disodium hydrogen phosphate 0.~00% by weight Distilled Water 100 % by weight q`he solution was prepared by dissolving the salts in water and was then put up in 10 m] lots in polypropylene/
aluminium/nylon sachets which were then sterilized b~ auto~
claving. ~he pX o~ the bulk solution was 7.3, that of the sterillzed so]utlon 7.3 and thatof the spen-t solution (i~e.
one obtained by reaction with a PVP/I2 tablet) was 7.1.

xample 2 Sodium ~ormate tablets for addi-tion to 10 ml ]ots of 20 50 ppm PVP/I2 solution had the followiLg composition:
Sodium formate 50 mg/tablet Sodium dihydrogen phosphate 2.3 mg/tablet Disodium hydrogen phosphate 10 mg/tablet Borlc acid 2.5 mg/tablet Sodium chloride 35.2 mg/tablet 1053~8 The tablets were prepared by mixing the powdered ingredients and tabletting the mixed powders using 3/16 inch punches.
The PVP/I2 solution for use with the above tablets is made up by adding 0.05 ml of a 1% available iodic solution aqueous solution of P~P/I2 (e.g. from a dropper) to 10 ml of distilled water (e.g. contained in a lens case).
Example 3 An aqueous sterilization solution is made up by adding 0.05 ml of a 1% available iodic aqueous solution of PVP/I2 to 10 ml of the sodium formate solution of Example 1.
The sterilizing activity of the combined tablets and solution of Example 1 was tested by preparing a test solution from two tablets and two sachets to give a total volume of test solution of 20 ml. This volume of solution was employed since the test procedure required removal of 2 ml aliquot at periodic intervals.
The solution was tested individually for activity against the following organisms:-Staphyloco_cus aureus NCTC 6571 Pseudomonas aeruginosa NCTC 6780 Escherischia coli NCTC 86, and Candida Albicans The tests were carried ~y adding, to 20 ml of the test solution 105 _ 106 organism/ml of the organism by the addition of a standardised suspension of the organism in 0.25 strength Ringer solution.

lOS3S78 The innoculated solutions were maintained at 24-26C
and 2 ml aliquots removed at 1 minute after addition of the test organislll and 15 minutes after addition of the test or~anism.
The aliquots (in 2 x 1 ml lots) were transferred to 18 ml of Neutralizing medium and then incubated at 37C for 40 hours to establish the prèsence or absence of organisms. i -In a similar set of tests the forrnate solution was replaced by a solution containing the buffer only.
` The results are shown in the followin~ Table.
-- ~
Time (mins) to s erilize solution Test organismsPVPI2/Formate PvpI2/Buffer S. aureus lS 15 P. acruginosa 15 15 E. coli 15 15 ~ bicans <1 <1 ¦

'~, `

-~

~he a~o~e tcs-ts l~cre rcpcatcd e~cep-t that a pair oE
soft contacl lenses (hereinafter referred to as lenses A and ~) wexe present in -the solution. ~he results obtained were subs-tantially the sa~e. ~ens A was formed of poly (hydroxye-thyl methacr~late) cross-linked wi-th 0.27-0.~% of e-thylene glycol dimethacrylate. ~ens ~ was found of a copolymer of 2-hydroxy-l-methox~-prop~ l methacrylate vinyl pyrrolidone and ~ethyl methacrylate containing ~0% of vinyl pyrrolidone.

A number of experiments were carried out to investigate the rate of decomposition of iodophor solutions using various reducing agen-ts. ~he results are summarized in the following table.

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NOT~S.

(1) Experiment carried out in presence of lens A, le~s clear after 2 hours.
(2) ~ntorax believed to be an 12/ C0880 complex (C0880 is nonylphenoxy - polyox~ethylene ethanol).
Experiment carried out in presence of lens A, lens clear within 1 hour.
(3) ~xperiment carried out in presence of lens A, lens clear within 2 hours.

(4) ~xperiment carried out in presence of lens ~, lens clear after 5 hours.
~ xperiment carried out in presence of "Soflon"
lens (believed to contain at least 35~ vinyl pyrrolidone,) lens ~till yellow after 24 h~ur~.
(6) Wescodyne believed to comprise polythoxypoly-prox~ ethanol/I2 - 7.75%, nonyl phenyl ether of propyk~e glycol/I2- 3.7y, water and acid to 10~/o. Experiment carried out in presence of lens A, lens clear after 3 hours.
(7) ~xperiment carried out in presence of lens B, lens clear within 3 hours.
~8)Dermaran is stated to be a complex of iodine - with 10% nonionic surface active agent and 10% acetone.
~xperiment carried out in presence of lens A, lens clear after 3 hours.
~9) ~xperiment carri~d out i~ presence of lens lens clear within 6 hours.

(10) Ioprep i~ believed to be an iodine co~plex with l~/o of nonylphenoxy polyethylerle glycol. E,xp~rimen-t carried out in presence of lens A, lens clear after 2 hours.

(11) Experi~ent carried out in presence of len~ ~ lens clear after 5 hours.

In a further series of ex~eriments the uptake of iodine from a PVP/12 solution into lenses and discs made of polymer A and polymer ~.

~o determine the uptake of iodine by the lenses, the colour change was observed spectrophotometrically.

q`he lenses were soaked in 50 ppm PVP/12 solutions and th~ i,odine uptake by the lens measured. Discs of polymer ~ and polymer ~ that were cut from cas-t sheeting were also treated in this way. All readings were at ~75 nm.
': .
q'he polymer A samples reached a maximum value o~
about 2 mg 12/ml of lens material in 2 hours. ~his is a conce~tration of about 40 times that of the ~oaking solu-tion. ~here appeared to be no signilicant different between the polymer~ lenses and discs once corrected for thickness. Polymer ~ lenses concentrated the iodine to such an extent that the colour produced was too s-trong to be measured after 30 minutes.

q`he release of iodine was observed under the s~me conditio~s as only a tablet containing 50 mg of sodium formate (as accured in Example 2) was added at zero time, this dissolved completely in about 15 minutes. Qgain, both pol~er A and polymer ~ lenses and discs were used.

. lOS3578 ~he iodine content of the PVP solut-ion decreases to zero over 1 hour. ~he polymer A le.nses and discs conccn-trate the iodine solution approximately ei~ht times tha-t of the starting soluti.on, giving a maximum value of 400 ppm 12 which decreases -to zero over 3 hours~ ~he polymer lenses and discs concentrate the iodine even further, approximat-ely 20 -times that of -~he original solu-tion., approximat~ly 2.5 times that of polymer ~, giving a maximum value of 1,000 ppm decreasing to zero in about 8 hours. ~he polymer B film appears to release the iodine slightly fas-ter than -the pol~mer lenses.
.

. - 27 -~53578 In furthcr experiments the uptake of Iodine from the iodophor, namely Wescodyne and Antorax a-t 50 ppm available iodine levels into lenses made of polymers A and ~ was investigated. l'he experiments were carried out at ambient temperature and the iodine was induced by the addition of one tablet according to ~Xamp]e 2.
~he results are summerised in the fo]lowing table.

_ ___ i Time taken to reduce maximum Iodophu ~ens. Maximum I I2 concentra~ on to concentra~o~ _

5~t 25~ Zero _ _ _ .
PolymeI i Wescody~n)e A 200 30 40 80 1. Polymer 1000 90 140 ~ 5 hrS
Antorax Polymer 1&0 50 20 40 t ~ ~r~dc~r~ ) A
~ Antorax Polymer1800 55 130~ 5 hrs~
.' /~ ~ I . ., . _ ' __.

l. ~he ocular response of the PVPI2/forma~ s~stem of ~xam~le l used with Snoflex and polymer A lenses has been assessed in a 28 day lens wearing study in 10 rabbits.
For each material, all eyes were ~itted with lenses, which were worn 6 hours dail~ for 28 ccnsecutive days.
When removed from the eyes, all left lenses were sterilised in PVP/~2~forma-~e, and all righ-t lenses were sterilised by boiling in saline.
~o evidence of ocular irritation was seen with the slit l~np.
2. The oculal respon~e ot' the above system has been assessed in a s-tudy using 12 volvnteers (6 polyme,r A;

6 Snol'lex).
No evidence of ocular di.scomfort has been recorded in 3 polyrner A and 3 Snoflex wearers following 7 days use o.t.' the test solution.
In tests to establisll the long term effect of' the ste,ilization system according to -the invention lenses made of polyme~ A a~d B were repeated'ly il~nersed in solution made by combining -the tablets of and sachets of Exarnple 1 for a period of 4 hours. ~his procedure was repeated a -total of ~00 times and no appreciable change in wei~ht or other characteristics were noted for the ., lenses.

~ 29 - . . - . . , ~ , . .. - ~: .

Claims (18)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method of sterilizing an article which comprises contacting the article with an aqueous solution of an iodophor also containing sufficient of an organic aldehydic reducing agent to reduce the available iodine level of the solution to substantially zero within a period of from 30 minutes to 8 hours at 20 to 25°C; the reaction products of the iodophor and the reducing agent being non-toxic and non-irritant.

2. A method as claimed in claimed 1 in which the iodophor comprises a complex of iodine with a complexing agent selected from the group consisting of hydrophilic polymers and surface active agents.

3. A method as claimed in claim 2 in which the iodophor is a polyvinylpyrrolidone/iodine complex.

4. A method as claimed in claim 1 in which the solution contains sufficient reducing agent to reduce the available iodine level of the solution to substantially zero within a period of fro 1 to 4 hours.

5. A method as claimed in claim 1 in which the sterilizing solution contains sufficient iodophor to give an initial available iodine concentration of at least 20 ppm.

6. A method as claimed in claim. 5 in which the sterilizing solution contains sufficient iodophor to give an initial available iodine concentration of from 20 to 300 ppm.

7. A method as claimed in claim 6 in which the sterilizing solution contains sufficient iodophor to give an initial available iodine level of from 25 to 100 ppm.

8. A method as claimed in claim 1 in which the reducing agent is selected from the group consisting of reducing agent sugars and reducing organic carboxylic acids and salts thereof.

9. A method as claimed in claim 8 in which the reducing agent is sodium formate.

10. A method as claimed in claim 1 in which the reducing agent is present in an amount of from 10 to 800 moles, per mole of iodine in iodophor.

11. A method as claimed in claim 10 in which the reducing agent is present in an amount of from 100 to 400 moles per mole of iodine in the iodophor.

12. A method as claimed in claim 1 in which the article to be sterilized is formed of a hydrophilic polymer, the iodophor is a complex of iodine with a hydrophilic polymer or a nonionic surface active agent and reducing agent is formic acid or an alkali metal salt thereof.

13. A method as claimed in claim 12 in which the article is a contact lens.

14. A method as claimed in claim 12 in which the solution also contains a buffering agent to give the solution a final pH of from 5 to 8.

15. A method as claimed in claim 14 in which the solution contains a buffering agent in an amount sufficient to give the solution a final pH of from 7 to 7. 5.

16. A method as claimed in claim 12 in which the solution also contains a tonicity adjusting agent.

17. A method as claimed in claim 1 in which the sterilizing solution is prepared by adding a solid unit dosage form containing the iodophor to an aqueous solution of the reducing agent.

18. A method as claimed in claim 1 in which the sterilizing solution is prepared by adding a solid unit dosage for containing the reducing agent to an aqueous solution of the iodophor.