(19)
`
`3
`
`
`
`Europaisches Patentamt
`European Patent Office
`Office europeen des brevets ien des brevets
`
`
`^
`
`E P 0 9 2 3 9 5 0 A 2
`
`(12)
`
`EUROPEAN PATENT A P P L I C A T I O N
`
`(43) Date of publication:
`23.06.1999 Bulletin 1999/25
`
`(21) Application number: 98310417.5
`
`(22) Date of filing: 18.12.1998
`
`(84) Designated Contracting States:
`AT BE CH CY DE DK ES Fl FR GB GR IE IT LI LU
`MC NL PT SE
`Designated Extension States:
`AL LT LV MK RO SI
`
`(30) Priority: 18.12.1997 J P 34927397
`30.10.1998 JP 31017598
`
`(71) Applicant: TOMEY CORPORATION
`Nagoya-shi, Aichi-ken (JP)
`
`(72) Inventors:
`• Ibaraki, Keiko, c/o TOMEY CORP. General-Lab.
`Nagoya-shi, Aichi-ken (JP)
`
`(54)
`
`Liquid agent for contact lens
`
`A liquid agent for a contact lens, containing at
`(57)
`least one disinfecting component selected from the
`
`(51) |nt CI * A61 L 2/18, C1 1 D 3/48,
`C1 p 3/33 C-| -| D 3/37
`
`• Mizuno, Hideto, c/o TOMEY CORP. General-Lab.
`Nagoya-shi, Aichi-ken (JP)
`• Goshima, Takehiko,
`c/o TOMEY CORP. General-Lab.
`Nagoya-shi, Aichi-ken (JP)
`• Shimbo, Keiko, c/o TOMEY CORP. General-Lab.
`Nagoya-shi, Aichi-ken (JP)
`
`(74) Representative:
`Paget, Hugh Charles Edward et al
`MEWBURN ELLIS
`York House
`23 Kingsway
`London WC2B 6HP (GB)
`
`group consisting of Polyquaternium-6, Polyquaternium-
`7, Polyquaternium-16 and Polyquaternium-22, and a
`nonionic tonicity agent and/or an amino acid.
`
`CM
`<
`O
`IO
`O)
`CO
`CM
`O)
`o
`a .
`LU
`
`Printed by Jouve, 75001 PARIS (FR)
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1007, p. 1 of 17
`
`

`

`Description
`
`EP 0 923 950 A2
`
`[0001] The present application is based on Japanese Patent Applications Nos. 9-349273 and 10-310175 filed De-
`cember 18, 1997 and October 30, 1998, respectively, the content of which is incorporated hereinto by reference.
`
`BACKGROUND OF THE INVENTION
`
`Field of the Invention
`
`[0002] The present invention relates to a liquid agent for a contact lens, which exhibits an excellent disinfecting effect
`and assures a sufficiently high degree of safety to the eyes of the user, and which liquid agent can be suitably used
`as a cleaning and storing or preserving liquid for the contact lens.
`
`Discussion of the Related Art
`
`5
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`20
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`25
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`[0003] The contact lenses worn on the eyes of the user is likely to be soiled with deposits such as proteins and lipids
`which are included in the tear. The contact lenses need to be cleaned to remove such deposits therefrom. Further,
`during a long period of use of the contact lenses, microorganisms such as bacteria tend to adhere to and proliferate
`on the surfaces of the contact lenses while the contact lenses are stored after they have been removed from the eyes.
`Such microorganisms may cause infectious diseases, giving adverse influences on the eyes of the user. In view of the
`above, the contact lenses need to be cleaned before they are worn on the eyes. In particular, it is indispensable to
`disinfect soft contact lenses since the microorganisms are likely to proliferate on the surfaces of the soft contact lenses
`more often than those of the hard contact lenses, increasing a risk of causing the infectious diseases.
`[0004] For disinfecting the contact lenses, there have been practiced a thermal disinfecting method using a suitable
`boiling device for boiling the contact lenses, and a chemical disinfecting method using a suitable chemical disinfectant.
`The thermal disinfecting method requires a relatively long period of time to disinfect the contact lenses, using the boiling
`device. Accordingly, in recent years, the chemical disinfecting method has been attracting a greater attention than the
`thermal disinfecting method.
`In the chemical disinfecting method, the contact lenses are immersed in a liquid agent which exhibits a chem-
`[0005]
`ical disinfecting effect, so that the contact lenses can be sufficiently disinfected. Such a liquid agent is required to
`exhibit not only a high disinfecting effect, but also low toxicity to the eyes since the contact lenses are immersed in the
`liquid agent for a long time for disinfection.
`[0006] As the chemical disinfectant used in the chemical disinfecting method, chlorhexidine, quaternary ammonium
`salt and thimerosal are disclosed in JP-A-52-1 09953, JP-A-62-153217 and JP-A-63-59960. In order to obtain a suffi-
`ciently high disinfecting effect, these chemical disinfectants are included generally at a relatively high concentration in
`the liquid agent. In this case, the chemical disinfectants are likely to be uptaked in or adsorbed on the contact lenses,
`especially the soft contact lenses. It is reported that the eyes of the lens wearer suffer from troubles due to direct
`contact thereof with the contact lenses on which the disinfectants are adsorbed after the disinfecting treatment ("Journal
`of Japan Contact Lens Society" 34:267-276, 277-282, 1992, 35:219-225, 1993, 36:57-61, 1994, 37:35-39, 154-157,
`1995).
`[0007] To avoid the above problem, the contact lens may be disinfected by using a contact lens liquid agent in which
`the chemical disinfectant (germicide) is included at a relatively low concentration for assuring safety of the eyes. In
`this case, however, the disinfecting effect to be exhibited by the liquid agent is inevitably lowered, whereby the liquid
`agent cannot provide a satisfactory disinfecting or sterilizing effect, causing contamination of the contact lenses by the
`45 microorganisms.
`In order to solve the problem of adsorption of the disinfectants on the contact lenses, it is proposed to use a
`[0008]
`high molecular weight quaternary ammonium which exhibits a high disinfecting effect. By using the quaternary ammo-
`nium having a high molecular weight, the entry of the germicide into the contact lens is prevented. Examples of such
`a method are disclosed in JP-B-2-54804 which teaches the use of Polyquaternium-1 , and U.S. Patents Nos. 4361548
`and 4443429, which teach the use of Polyquaternium-6. None of the germicides disclosed in these patents, however,
`exhibit a satisfactory disinfecting effect when used in the formulations and compositions taught in those patents. There-
`fore, it has been desired to provide a contact lens liquid agent capable of exhibiting a sufficiently high disinfecting effect
`and a high degree of safety to the eyes.
`
`30
`
`35
`
`40
`
`so
`
`55
`
`SUMMARY OF THE INVENTION
`
`It is therefore an object of the present invention to provide a liquid agent for a contact lens, which is capable
`[0009]
`of providing sufficiently high disinfecting efficacy while having a low degree of toxicity to the eyes, and which can be
`
`2
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` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1007, p. 2 of 17
`
`

`

`EP 0 923 950 A2
`
`safely used in disinfecting the contact lens.
`[0010] The inventors have made an extensive study on various known cation polymers which are considered to have
`an antimicrobial activity or a disinfecting effect, in an attempt to utilize those cation polymers in a contact lens liquid
`agent as a disinfecting or sterilizing component. The study has revealed that some kinds of the cation polymers which
`are used as the materials of hair-care and skin-care cosmetics and which are called "Polyquaternium" under the CTFA
`(The Cosmetic Toiletry and Fragrance Association, Washington D.C.), have a low degree of toxicity to the eyes and a
`high degree of safety suitable as the disinfecting component to be used in the contact lens liquid agent. Further, the
`inventors have found that a combined use of a suitable cation polymer with a nonionic tonicity agent and/or an amino
`acid in the contact lens liquid agent effectively intensifies or enhances the antimicrobial activity or the disinfecting action
`of the cation polymer.
`[0011] The above object of the present invention may be attained according to the principle of the invention, which
`provides a liquid agent for a contact lens, containing at least one disinfecting component selected from the group
`consisting of Polyquaternium-6, Polyquaternium-7, Polyquaternium-16 and Polyquaternium-22, and a nonionic tonicity
`agent and/or an amino acid.
`[0012] The contact lens liquid agent according to the present invention contains suitably selected Polyquaternium
`as a component effective for disinfecting or sterilizing the contact lens, so that it exhibits an excellent disinfecting action
`and a high degree of safety owing to the considerably low toxicity of the Polyquaternium. Further, the combined use
`of the Polyquaternium and the nonionic tonicity agent and/or the amino acid provides a synergistically enhanced dis-
`infecting effect, whereby the present contact lens liquid agent can exhibit an excellent disinfecting effect even when
`the concentration of the Polyquaternium included therein is relatively low.
`[0013] Preferably, the disinfecting component is contained in the liquid agent at a concentration of 0.00000001-1.0
`w/v%, and the nonionic tonicity agent and/or the amino acid is/are contained at a concentration of 0.01 -20 w/v%.
`In the present invention, at least one of glycerin, propylene glycol and mannitol is preferably used as the
`[0014]
`nonionic tonicity agent while a low molecular weight amino acid having a molecular weight of 75-250 is preferably used
`as the amino acid. This arrangement is effective to synergistically enhance the disinfecting activity of the suitably
`selected Polyquaternium.
`[0015] The present contact lens liquid agent may further contain a buffer. Owing to the use of the buffer together
`with the suitable Polyquaternium (as the disinfecting component) and the nonionic tonicity agent and/or the amino acid,
`the disinfecting and sterilizing effect to be exhibited by the Polyquaternium is significantly enhanced. As the buffer, a
`borate buffer, a phosphate buffer, a citrate buffer or a tris(hydroxymethyl)aminomethane buffer is preferably used.
`
`5
`
`10
`
`is
`
`20
`
`25
`
`30
`
`DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
`
`35
`
`[0016] The disinfecting component of the present contact lens liquid agent is selected from substances called "Poly-
`quaternium" under the CTFA indicated above. In other words, at least one of Polyquaternium-6, Polyquaternium-7,
`Polyquaternium-16 and Polyquaternium-22 is used as the disinfecting component. Owing to the combined use of the
`suitably selected Polyquaternium and a nonionic tonicity agent and/or an amino acid, the present contact lens liquid
`agent exhibits a synergistically enhanced disinfecting effect.
`[0017] The above-described Polyquaternium is explained in detail on pages 462-463 of "CTFA International Cos-
`40 metic Ingredient Dictionary". For instance, the Polyquaternium-6 is a homopolymer of dimethyl diallyl ammonium chlo-
`ride. The Polyquaternium-7 is a polymeric quaternary ammonium salt formed of acrylamide and dimethyl diallyl am-
`monium chloride. The Polyquaternium-1 6 is a polymeric quaternary ammonium salt formed of methylvinylimidazolium
`chloride and vinylpyrrolidone. The Polyquaternium-22 is a copolymer of dimethyl diallyl ammonium chloride and acrylic
`acid.
`[0018] Among various kinds of the Polyquaternium indicated above, the Polyquaternium-6 which is the homopolymer
`of dimethyl diallyl ammonium chloride, and the Polyquaternium-7 which is a copolymer of dimethyl diallyl ammonium
`chloride are preferably used in the present contact lens liquid agent since they exhibit a high disinfecting effect and
`assure a high degree of safety. As the Polyquaternium-6, "Merquat-100" which is available from CALGON CORPO-
`RATION, U.S.A., and which is used as a material of hair-care and skin-care products is preferably used.
`[0019] The Polyquaternium suitably selected as the disinfecting component is used in combination with the nonionic
`tonicity agent and/or the amino acid, so that the antimicrobial action of the Polyquaternium is effectively enhanced, so
`that the contact lens liquid agent of the present invention can exhibit a sufficiently high disinfecting effect even if the
`concentration of the disinfecting component is considerably low, e.g., as low as 0.00000001 w/v%, as compared with
`that of the conventional contact lens liquid agents. In the present invention, the disinfecting component is included in
`the contact lens liquid agent at a concentration of generally at least 0.00000001 w/v%, preferably at least 0.0000001
`w/v%, more preferably at least 0.000001 w/v%. The upper limit of the disinfecting component included in the present
`contact lens liquid agent is generally 1 .0 w/v%, preferably 0.1 w/v%, more preferably 0.01 w/v%.
`[0020] The nonionic tonicity agent used in combination with the suitable Polyquaternium as the disinfecting compo-
`
`45
`
`so
`
`55
`
`3
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1007, p. 3 of 17
`
`

`

`EP 0 923 950 A2
`
`nent is selected from among various known nonionic tonicity agents such as glycerin, propylene glycol, mannitol,
`polyethylene glycol (having an average molecular weight of 100-400), glucose, diethylene glycol, sorbitol, xylitol and
`cyclodextrin. In addition, any other known nonionic tonicity agents may be used, provided that they assure sufficiently
`high safety suitable for the present contact lens liquid agent. Any one of, or any combination of, those nonionic tonicity
`agents may be employed. In particular, at least one of glycerin, propylene glycol and mannitol is preferably used as
`the nonionic tonicity agent to be included in the present contact lens liquid agent. The nonionic tonicity agent is also
`effective to adjust the osmotic pressure of the contact lens liquid agent. The osmotic pressure of the present contact
`lens liquid agent is adjusted to within a range of 200-400 mOsm, which substantially corresponds to a physiological
`osmotic pressure, to thereby prevent the eye irritation which would be otherwise caused when the contact lenses which
`have been treated by the liquid agent are worn on the eyes.
`[0021] The amino acid used in combination with the suitable Polyquaternium as the disinfecting component is se-
`lected from among various known compositions, each of which has a carboxyl group and an amino group in each
`molecule thereof. As the amino acid, it is preferable to use a low molecular weight amino acid having a molecular
`weight of 75-250 such as alanine, a-aminoadipic acid, a-aminobutyric acid, a-aminoisobutyric acid, arginine, aspar-
`agine, aspartic acid, isoleucine, creatine, glutamine, glutamic acid, glycine, histidine, cystine, tyrosine, tryptophan,
`valine, methionine, lysine, leucine, ornithine, phenylalanine, proline, phosphoserine, sarcosine, threonine, cysteine,
`serine, and salts thereof. Particularly preferably used are sodium L-glutamate, glycine, DL-alanine, DL-serine, L-his-
`tidine and L-glutamine. In particular, the sodium L-glutamate or glycine is preferably used as the low molecular weight
`amino acid. The amino acid also functions as a buffer, and it does not give an adverse influence on the size of the
`contact lens which is immersed in the liquid agent, so that the amino acid can be preferably used in the present contact
`lens liquid agent.
`[0022] The nonionic tonicity agent and/or the amino acid used in combination with the suitable Polyquaternium is/
`are included in the present contact lens liquid agent generally at a concentration of 0.01-20 w/v%, preferably at a
`concentration of 0.05-10 w/v%. If the amount of the nonionic tonicity agent and/or the amino acid is too small, the
`osmotic pressure of the contact lens liquid agent is undesirably low. On the other hand, an excessive amount of the
`nonionic tonicity agent and/or the amino acid increases the osmotic pressure of the liquid agent to an undesirably high
`level.
`[0023] The pH of the present contact lens liquid agent is adjusted to be held within a substantially neutral range,
`namely, in a range of 5-9, preferably in a range of 6-8, to permit the disinfecting component to exhibit a sufficiently high
`disinfecting and sterilizing effect while preventing the eye irritation when the contact lenses treated by the liquid agent
`are worn on the eyes. The pH value outside the above range of 5-9 may cause an eye irritation and other troubles.
`[0024] For effectively keeping the pH of the present contact lens liquid agent in the above range of 5-9 which assures
`the safety of the eyes, at least one buffer is added to the liquid agent. The buffer is added to the present contact lens
`liquid agent in orderto permit the disinfecting component to exhibit a satisfactory disinfecting and sterilizing effect while
`avoiding the eye irritation when the contact lenses which have been treated by the contact lens liquid agent are worn
`on the eyes.
`[0025] The buffer to be added to the present contact lens liquid agent may be suitably selected from among any
`known buffers such as a borate buffer, a phosphate buffer, a tris(hydroxymethyl)aminomethane buffer, and a citrate
`buffer. The buffer is included in the contact lens liquid agent in an amount of 0.05 w/v% or more, preferably 0.1 w/v%
`or more, since the buffering action of the buffer tends to be insufficient if the amount of the buffer is excessively small.
`On the other hand, an excessive amount of the buffer may cause an eye irritation when the contact lenses treated by
`the contact lens liquid agent are worn on the eyes. In view of this, the buffer is added to the liquid agent in an amount
`of not larger than 1 .2w/v%, preferably not larger than 0.8 w/v%.
`[0026] The present contact lens liquid agent may further contain a surface active agent for improving a cleaning
`effect to remove deposits such as lipids adhering to the contact lenses, and for increasing the viscosity of the liquid
`agent. Any kinds of the surface active agent such as cationic, anionic, amphoteric and nonionic may be employed at
`concentrations which do not adversely influence the effect of the present invention, as long as the selected surface
`active agent is safe to the living body without adversely influencing the material of the contact lenses.
`[0027] The present contact lens liquid agent may further contain other known additives such as a chelating agent,
`a thickener and a protein removing agent, provided that they are safe to the living body and do not give an adverse
`influence on the material of the contact lenses. The additives may be employed in combination, as needed, in amounts
`that do not inhibit the effect of the present invention.
`[0028] The present contact lens liquid agent which contains the suitably selected Polyquaternium (as the disinfecting
`component), the nonionic tonicity agent and/or the amino acid is/are easily prepared in a way as usually used for
`preparing an aqueous solution, without requiring any special procedure. Namely, the present contact lens liquid agent
`is obtained by dissolving each component in a predetermined amount of purified sterile water. The obtained contact
`lens liquid agent is transparent or clear, and is subjected to sterile filtration as needed.
`[0029] The contact lens is treated with the thus obtained liquid agent in the following manner. The contact lens which
`
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`

`

`EP 0 923 950 A2
`
`has been removed from the eye is accommodated in a container filled with the present contact lens liquid agent. The
`contact lens is immersed for disinfection in the contact lens liquid agent for a time period of from 10 minutes to 24
`hours, preferably from 30 minutes to 8 hours, more preferably from 1 hour to 6 hours. It is to be understood that the
`contact lens may be otherwise treated using the present contact lens liquid agent.
`[0030] According to the procedure described above, the contact lens can be easily and effectively disinfected without
`using the conventionally required boiling device. Since the suitably selected Polyquaternium as the disinfecting com-
`ponent assures a high degree of safety to the eyes, the contact lens can be disinfected with safety without causing
`any troubles with the eyes even when the contact lens is immersed in the present contact lens liquid agent for a relatively
`long period of time.
`[0031] The contact lens liquid agent according to the present invention can be applied to any known kinds of contact
`lenses such as low-water-content and high-water-content soft contact lenses, and hard contact lenses, irrespective of
`the materials of those contact lenses.
`[0032] To further clarify the concept of the present invention, some examples of the invention will be described. It is
`to be understood that the invention is not limited to the details of the illustrated examples, but may be embodied with
`various changes, modifications and improvements, which may occur to those skilled in the art without departing from
`the scope of the invention defined in the attached claims. The percentage in the following examples are on a weight/
`volume (w/v) basis unless otherwise specified.
`
`-Test for checking the disinfecting efficacy-
`
`[0033] As the test bacteria or fungi, S. m. (Serratia marcescens ATCC 1 3880) or C. a. (Candida albicans ATCC
`10231) was used. The S. m. was cultured by using a soybean-casein medium at 30°C for 24 hours while the C. a. was
`cultured by using a Glucose-Peptone medium at 30°C for 24 hours. Each of the thus cultured S. m. and C. a. was
`suspended with saline, to thereby provide a bacteria or fungi suspension of 108 cfu/ml.
`[0034] To evaluate the disinfecting effect of the present contact lens liquid agent, 1 0 ml of the liquid agent was poured
`into a disinfected test tube. 0.05 ml of the bacteria or fungi suspension prepared as described above was introduced
`into the test tube, and the test tube was stored in a thermostat kept at 23°C for a suitable period of time. Thereafter,
`a predetermined amount of the mixture was taken out of the test tube, and diluted with sterilized saline. For 1 ml of the
`diluted solution, a viable cell count was measured by a mixing dilution method. In the mixing dilution method, the mixture
`including the bacteria (S.m.) was cultured by using the soybean-casein medium at 30°C for 3 days while the mixture
`including the fungi (C.a.) was cultured by using the Glucose-Peptone medium at 30°C for 5 days. On the basis of the
`measured viable cell count, there was calculated a viable cell count of the mixture of the contact lens liquid agent and
`the bacteria or fungi suspension a predetermined time after mixing of the liquid agent and the bacteria or fungi sus-
`pension. Then, an amount of reduction of the bacteria or fungi was calculated in logarithm according to the following
`equation.
`
`Reduction amount [in logarithm] =
`
`LOG (the viable cell count per 1 ml of each bacteria or
`
`fungi suspension immediately after the preparation) -
`
`LOG (the viable cell count per 1 ml of each bacteria
`
`or fungi suspension after the treatment by the contact
`
`lens liquid agent)
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`<Example 1>
`
`55
`
`[0035] To examine the disinfecting efficacy of the present contact lens liquid agent, the following experiment was
`conducted. Initially, various specimens (Nos. 1-10) of the contact lens liquid agent were prepared so as to have re-
`spective compositions as indicated in the following Tables 1 and 2, by dissolving respective components in purified
`sterile water. As the disinfecting component, "Merquat 550" available from CALGON CORPORATION, U.S.A., "Luvi-
`quat FC 370" available from BASF, Germany, "SWANOL AM-101" available from Nikko Chemicals, Co., Ltd, Japan,
`"Merquat 280" and "Merquat 100" both available from CALGON CORPORATION, U.S.A. were used. Described in
`detail, the Merquat 550 is Polyquaternium-7 which is a copolymer of acrylamide and dimethyl diallyl ammonium chloride.
`
`5
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`

`IU
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`
`EP 0 923 950 A2
`
`The Lubiquat FC 370 is Polyquaternium-16 which is a copolymer of methylvinylimidazolium chloride and vinylpyrro-
`lidone. The SWANOL AM-101 is 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazoliumbetaine. The Merquat 280 is
`Polyquaternium-22 which is a copolymer of dimethyl diallyl ammonium chloride and acrylic acid. The Merquat 100 is
`Polyquaternium-6 which is a homopolymer of dimethyl diallyl ammonium chloride.
`[0036] Each of the thus prepared specimens of the contact lens liquid agent was examined of its disinfecting efficacy
`against the C.a. Namely, the fungi reduction amount four hours after mixing with the fungi suspension was obtained
`in accordance with the above-described disinfecting efficacy test. The results are also indicated in the Tables 1 and 2.
`
`T A B L E
`
`S p e c i m e n Nos .
`2
`
`3
`
`4
`
`1
`
`b o r i c a c i d
`
`(%)
`
`0.5
`
`0.5
`
`0.5
`
`0.5
`
`5
`
`0 . 5
`
`b o r a x
`
`(%)
`
`0 . 1 1
`
`0 . 1 1
`
`0 . 1 1
`
`0 . 1 1
`
`0 . 1 1
`
`s o d i u m c h l o r i d e
`
`fi
`o
`Tj g l y c e r i n
`■H
`o M e r q u a t 550
`Cu
`e
`0 L u v i q u a t FC 370
`
`(%)
`
`(%)
`
`(%)
`
`0 . 1 1 5
`
`0 . 6 3
`
`0 . 1 1 5
`
`0 . 6 3
`
`0 . 1 1 5
`
`1.7
`
`0.1
`
`0 . 1
`
`1.7
`
`1 . 7
`
`(%)
`
`0 . 0 1
`
`0 . 0 1
`
`SWANOL AM-101
`
`(%)
`
`f u n g i r e d u c t i o n a m o u n t
`(LOG c f u / m l )
`
`4.5
`
`0.1
`
`1.2
`
`0.2
`
`0 . 1
`
`0 . 3
`
`3
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1007, p. 6 of 17
`
`

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`5
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`10
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`25
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`55
`
`EP 0 923 950 A2
`
`T A B L E
`
`2
`
`S p e c i m e n Nos .
`7
`8
`
`9
`
`6
`
`b o r i c a c i d
`
`(%)
`
`0.5
`
`0.5
`
`0.5
`
`0.5
`
`b o r a x
`
`(%)
`
`0 . 1 1
`
`0 . 1 1
`
`0 . 1 1
`
`0 . 1 1
`
`s o d i u m c h l o r i d e
`
`g
`•H
`h g l y c e r i n
`tn
`Oj M e r q u a t 280
`0
`u M e r q u a t 100
`
`(%)
`
`(%)
`
`(%)
`
`1 0
`
`0 . 5
`
`0 . 1 1
`
`0 . 6 3
`
`(%)
`
`0 . 6 3
`
`0 . 6 3
`
`0 . 1 1
`
`2.0
`
`1 . 7
`
`0 . 0 0 1
`
`0 . 0 0 1
`
`0 . 0 0 1
`
`0 . 0 0 1
`
`SWANOL AM-101
`
`(%)
`
`f u n g i r e d u c t i o n a m o u n t
`(LOG c f u / m l )
`
`0 . 1
`
`0.3
`
`3.6
`
`0.1
`
`4.9
`
`0 . 1
`
`[0037] As is apparent from the results of the above Tables 1 and 2, the specimens Nos. 1 , 3, 7 and 9 of the contact
`lens liquid agent according to the present invention wherein the glycerin was added as the nonionic tonicity agent
`exhibited a significantly higher disinfecting effect than the specimens Nos. 2, 4, 8 and 10 of the contact lens liquid
`agent which did not include the glycerin. The disinfecting effect of the liquid agent specimens No. 5 and 6 which used
`the betaine substance as the disinfecting component was not improved even if the glycerin was added as the nonionic
`tonicity agent. It was thus confirmed that the betaine substance as the disinfecting component did not synergistically
`enhance the disinfecting effect even with the combined use with the nonionic tonicity agent (i.e., glycerin).
`
`<Example 2>
`
`[0038] To examine the influence of a buffer on the present contact lens liquid agent, three kinds of the liquid agent
`specimens Nos. 11-13 in the form of an aqueous solution were prepared, so as to have the respective compositions
`as indicated below.
`
`specimen No. 11 (pH = 7.2):
`0.001 %
`Merquat 100
`boric acid
`0.5 %
`borax
`0.11 %
`2.0 %
`glycerin
`
`specimen No. 1 2 (pH = 7.3)
`Merquat 100
`sodium dihydrogenphosphate (dihydrate)
`disodium hydrogenphosphate (dodecahydrate)
`glycerin
`
`0.001 %
`0.08 %
`0.52 %
`2.0 %
`
`7
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1007, p. 7 of 17
`
`

`

`EP 0 923 950 A2
`
`specimen No. 13 (pH = 7.3)
`Merquat 100
`tris(hydroxymethyl)aminomethane
`glycerin
`HCI
`
`0.001 %
`0.3 %
`2.0 %
`suitable amount
`
`[0039] These three specimens Nos. 1 1 -1 3 of the contact lens liquid agent were examined of their disinfecting effects
`against the S.m. and C.a., respectively. Namely, the bacteria and fungi reduction amounts two hours after mixing with
`the bacteria and the fungi suspensions were obtained. The results are indicated in the following Table 3.
`
`TABLE 3
`Specimen Nos.
`reduction amount of S.m. (Log cfu/ml)
`reduction amount of C.a. (Log cfu/ml)
`
`11
`4.1
`> 4.9
`
`13
`12
`> 4.9 > 4.9
`2.6
`3.5
`
`It will be understood from the above results that all of the borate buffer (included in the liquid agent specimen
`[0040]
`No. 11), the phosphate buffer (included in the liquid specimen No. 12) and the tris buffer (included in the liquid specimen
`No. 13) synergistically enhanced the disinfecting effect exhibited by the disinfecting component (i.e., Merquat 100).
`
`<Example 3>
`
`[0041] Specimens Nos. 14-19 of the contact lens liquid agent were obtained each as an aqueous solution, by using
`Polyq