AU2002239545A1 - Improved ophthalmic and contact lens solutions with a peroxide source and a cationic polymeric preservative - Google Patents
Improved ophthalmic and contact lens solutions with a peroxide source and a cationic polymeric preservativeInfo
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Description
Improved Ophthalmic and Contact Lens Solutions With a Peroxide Source and a Cationic Polymeric Preservative
Cross-Reference to Related Applications
This application claims the benefit of U.S. Provisional Patent Application Serial Nos. 60/246,689, filed November 8, 2000, 60/246,707, filed November 8, 2000, 60/246,708, filed November 8, 2000, and 60/246,709, filed November 8, 2000.
Background
This invention relates to ophthalmic solutions used to treat eyes, to deliver active pharmaceutical agents to eyes and to treat ophthalmic devices that in use directly contact corneal tissues. Ophthalmic solutions are used to regularly treat and condition eyes and articles and devices that are regularly used in eyes, such as contact lenses. Because of the intimate contact that such solutions have with corneal tissue, several problems or concerns are regularly presented. For instance, for solutions directly in contact with corneal tissue the compatibility of the solution with the tissue, its ability to not damage or irritate, is important. This compatibility issue is also important for solutions used to treat devices that contact corneal tissue, such as contact lenses and the like. Furthermore, prolonged contact with corneal tissue can lead to the accumulation of material on corneal tissue, or on devices in contact with the solution that then leads to adverse reactions.
Preservative efficacy is measured by the amount that a solution decreases the viability of bacterial or fungal populations. In general, there is an expected trade-off between preservative efficacy and corneal tissue compatibility, as well as "comfort." Furthermore, the field of the invention relates to preservative systems that are broad ranged, and effective against not only bacterial, but also fungal sources of infection.
U..S. Pat. No. 4.758.595 (Ogunbiyi, et al.) discloses that polyhexamethylene biguanide (PHMB) and its water-soluble salts can fulfill minimal disinfection and be harmless to the eye and the lens, if used with a specific buffer, a surfactant, and in specific concentrations.
International Patent Publication No. WO 91/01763 discloses that solutions having very low concentrations of peroxide, i.e., from 0.01 to 0.5 percent more preferably
0.05 to 0.2 percent can provide disinfection without requiring neutralization. Use of the present invention greatly enhances the microbiocidal efficacy of peroxide in such low concentrations.
The present invention relates to improved solutions used in ophthalmic applications, where the improvement is increased preservative and anti-microbial efficacy. In particular it has been found that solutions comprising low levels of polyhexamethylene biguinide (PHMB) and a peroxide source, show increased preservative and anti-microbial activity over state of the art ophthalmic solutions.
Summary of the Invention
The present invention relates to ophthalmic solutions that are broad ranged and effective in low concentrations relative to state of the art systems. In particular it has been found that ophthalmic solutions comprising 0.0100 to 0.0001 percent by weight of a peroxide producing agent and 0.1 to about 500 parts per million by weight (PPM) of a, cationic, polymeric preservative display an effective preservative capacity, and an increased capacity over state-of-the-art preservative systems.
The invention also relates to articles of manufacture that employ the solution in their operation. For instance, vials employed to store contact lenses for sale may be filled using the solution
Detailed Description of the Invention
The present invention relates to ophthalmic solutions that are broad ranged and effective in low concentrations relative to state of the art systems. In particular it has been found that ophthalmic solutions comprising comprising 0.0100 to 0.0001 percent by weight of a peroxide producing agent and 0.1 to about 500 parts per million by weight (PPM) of a cationic, polymeric display improved effective preservative capacity, and greater capacity over state-of-the-art preservative systems.
Peroxide sources include hydrogen peroxide, sodium persulfate, sodium perborate decahydrate, sodium peroxide and urea peroxide, peracetic acid, an organic peroxy compound,
The cationic polymeric preservative includes polymeric biguanides such as polymeric hexamethylene biguanides (PHMB), and combinations thereof. Such cationic polymeric biguanides, and water-soluble salts thereof, having the following formula:
wherein Z is an organic divalent bridging group which may be the same or different throughout the polymer, n is on average at least 3, preferably on average 5 to 20, and X1 and X2 are
One group of water-soluble polymeric biguanides will have number average molecular weights of at least 1 ,000 and more preferably will have number average molecular weights from 1 ,000 to 50,000. Suitable water-soluble salts of the free bases include, but are not limited to hydrochloride, borate, acetate, gluconate, sulfonate, tartrate and citrate salts.
The above-disclosed biguanides and methods of preparation are described in the literature. For example, U.S. Pat. No. 3,428,576 describes the preparation of polymeric biguanides from a diamine and salts thereof and a diamine salt of dicyanimide.
Most preferred are the polymeric hexamethylene biguanides, commercially available, for example, as the hydrochloride salt from Zeneca (Wilmington, Del.) under the trademark CosmocilTM CQ. Such polymers and water-soluble salts are referred to as polyhexamethylene (PHMB) or polyaminoptopyl biguanide (PAPB). The term
polyhexamethylene biguanide, as used herein, is meant to encompass one or more biguanides have the following formula:
wherein Z, X1 and X2 are as defined above and n is from 1 to 500.
Depending on the manner in which the biguanides are prepared, the predominant compound falling within the above formula may have different X1 and X2 groups or the same groups, with lesser amounts of other compounds within the formula. Such compounds are known and are disclosed in U.S. Pat. No. 4,758.595 and British Patent 1 ,432,345, which patents are hereby incorporated. Preferably, the water- soluble salts are compounds where n has an average value of 2 to 15, most preferably 3 to 12.
In another embodiment, a polymeric biguanide is used in combination with a bis(biguanide) compound. Polymeric biguanides, in combination with bisbiguanides such as alexidine, are effective in concentrations as low as 0.00001 weight percent (0.1 ppm). It has also been found that the bactericidal activity of the solutions may be enhanced or the spectrum of activity broadened through the use of a combination of such polymeric biguanides with alexidine or similar biguanides.
An optional non-biguanide disinfectant/gennicide can be employed as a solution preservative, but it may also function to potentiate, complement or broaden the spectrum of microbiocidal activity of another germicide. This includes microbiocidally effective amounts of germicides which are compatible with and do not precipitate in the solution, in concentrations ranging from about 0.00001 to about 0.5 weight percent, and more preferably, from about 0.0001 to about 0.1 weight percent. Suitable complementary germicidal agents include, but are not limited to, quaternary ammonium compounds or polymers, thimerosal or other phenylmercuric salts, sorbic
acid, alkyl triethanolamines, and mixtures thereof. Representative examples of the quaternary ammonium compounds are compositions comprised of benzalkonium halides or, for example, balanced mixtures of n-alkyl dimethyl benzyl ammonium chlorides. Other examples include polymeric quaternary ammonium salts used in ophthalmic applications such as poly[(dimethyliminio)-2-butene-1 ,4-diyl chloride], [4- tris(2-hydroxyethyl) ammonio]-2-butenyl-w-[tris(2-hydroxyethyl)ammonio]dichloride (chemical registry number 75345-27-6) generally available as polyquaternium 1 (r) from ONYX Corporation, or those described in U.S. Pat. No. 6,153,568.
The acid-addition salts of the germicides used in the present composition may be derived from an inorganic or organic acid. In most circumstances it is preferable that the salts be derived from an acid which is readily water soluble and which affords an anion which is suitable for human usage, for example a pharmaceutically-acceptable anion. Examples of such acids are hydrochloric, hydrobromic, phosphoric, sulphuric, acetic, D-gluconic, 2-pyrrolidino-5-carboxylic, methanesulphonic, carbonic, lactic and glutamic acids.
Peroxide sources may also be included in the formulations of the present invention and are exemplified by hydrogen peroxide, and such compounds , which provide an effective resultant amount of hydrogen peroxide, such as sodium perborate decahydrate, sodium peroxide, urea peroxide and peracetic acid, an organic peroxy compound.
The pH of the present solutions should be maintained within the range of 5.0 to 8.0, more preferably about 6.0 to 8.0, most preferably about 6.5 to 7.8. Suitable buffers may be added, such as boric acid, sodium borate, potassium citrate, citric acid, sodium bicarbonate, Bis-Tris Propane, TRIS, and various mixed phosphate buffers (including combinations of Na2HPO4, NaH2PO4 and KH2PO ) and mixtures thereof. Borate buffers are useful for enhancing the efficacy of PAPB. Generally, buffers will be used in amounts ranging from about 0.05 to 2.5 percent by weight, and preferably, from 0.1 to 1.5 percent.
The solutions of the present invention may further contain other additives including but not limited to buffers, tonicity agents, demulcents, wetting agents, preservatives,
sequestering agents (chelating agents), surface active agents, and enzymes.
Ophthalmologically acceptable chelating agents useful in the present invention include amino carboxylic acid compounds or water-soluble salts thereof, including ethylenediaminetetraacetic acid, nitrilotriacetic acid, diethylenetriamine pentaacetic acid, hydroxyethylethylenediaminetriacetic acid, 1 ,2-diaminocyclohexanetetraacetic acid, ethylene glycol bis (beta-aminoethyl ether) in N, N, N', N' tetraacetic acid (EGTA), aminodiacetic acid and hydroxyethylamino diacetic acid. These acids can be used in the form of their water soluble salts, particularly their alkali metal salts. Especially preferred chelating agents are the di-, tn- and tetra-sodium salts of ethylenediaminetetraacetic acid (EDTA), most preferably disodium EDTA (Disodium Edetate).
Other chelating agents such as citrates and polyphosphates can also be used in the present invention. The citrates which can be used in the present invention include citric acid and its mono-, di-, and tri-alkaline metal salts. The polyphosphates which can be used include pyrophosphates, triphosphates, tetraphosphates, trimetaphosphates, tetrametaphosphates, as well as more highly condensed phosphates in the form of the neutral or acidic alkali metal salts such as the sodium and potassium salts as well as the ammonium salt.
The solutions of the invention are compatible with both rigid gas permeable and hydrophilic contact lenses and other ophthalmic devices and instruments during storage, cleaning, wetting, soaking, rinsing and disinfection.
A typical aqueous solution of the present invention may contain additional ingredients which would not affect the basic and novel characteristics of the active ingredients described earlier, such as tonicity agents, surfactants and viscosity inducing agents, which may aid in either the lens cleaning or in providing lubrication to the eye. Suitable tonicity agents include sodium chloride, potassium chloride, glycerol or mixtures thereof The tonicity of the solution is typically adjusted to approximately 240-310 milliosmoles per kilogram solution (mOsm/kg) to render the solution compatible with ocular tissue and with hydrophilic contact lenses. In one embodiment, the solution contains 0.01 to 0.5 weight percent sodium chloride.
The solutions employed in the present invention may also include surfactants such as a polyoxyethylene-polyoxypropylene nonionic surfactant which, for example, can be selected from the group of commercially available surfactants having the name poloxamine or poloxamer, as adopted by The CTFA International Cosmetic Ingredient Dictionary. The poloxamine surfactants consist of a poly(oxypropylene)- poly(oxyethylene) adduct of ethylene diamine having a molecular weight from about 7,500 to about 27,000 wherein at least 40 weight percent of said adduct is poly(oxyethylene), has been found to be particularly advantageous for use in conditioning contact lenses when used in amounts from about 0.01 to about 15 weight percent. Such surfactants are available from BASF Wyandotte Corp., Wyandotte, Mich., under the registered trademark "Tetronic". The poloxamers are an analogous series of surfactants and are polyoxyethylene, polyoxypropylene block polymers available from BASF Wyandotte Corp., Parsippany, N.J. 07054 under the trademark "Pluronic".
The HLB of a surfactant is known to be a factor in determining the emulsification characteristics of a nonionic surfactant. In general, surfactants with lower HLB values are more lipophilic, while surfactants with higher HLB values are more hydrophilic. The HLB values of various poloxamines and poloxamers are provided by BASF Wyandotte Corp., Wyandotte, Mich. Preferably, the HLB of the surfactant in the present invention is at least 18, more preferably 18 to 32, based on values reported by BASF.
Additional compatible surfactants that are known to be useful in contact wetting or rewetting solutions can be used in the solutions of this invention. The surfactant should be soluble in the lens care solution and non-irritating to eye tissues. Satisfactory non-ionic surfactants include polyethylene glycol esters of fatty acids, e.g. coconut, polysorbate, polyoxyethylene or polyoxypropylene ethers of higher alkanes (Cι2-C-|8). Examples of the class include polysorbate 20 (available from ICI Americas Inc., Wilmington, Del. 19897 under the trademark Tween ® 20), polyoxyethylene (23) lauryl ether (Brij ® 35), polyoxyethylene (40) stearate (Myrj ® 52), polyoxyethylene (25) propylene glycol stearate (Atlas ® G 2612). Brij ® 35, Myrj ® 52 and Atlas ® G 2612 are trademarks of, and are commercially available from, ICI Americas Inc., Wilmington, Del. 19897.
Various other surfactants suitable for in the invention can be readily ascertained, in view of the foregoing description, from McCutcheon's Detergents and Emulsifiers, North American Edition, McCutcheon Division, MC Publishing Co., Glen Rock, N.J. 07452 and the CTFA International Cosmetic Ingredient Handbook, Published by The Cosmetic, Toiletry, and Fragrance Association, Washington, D.C. however, the preferred surfactants are commercially available surfactants sold under the trademark cremaphor tm by BASF and which are polyoxyethoxylated castor oils.
Suitable viscosity inducing agents can include lecithin or the cellulose derivatives such as hydroxymethylcellulose, hydroxypropylcellulose and methylcellulose in amounts similar to those for surfactants, above.
EXAMPLE 1
A set of aqueous solutions containing Pluronic F127 (0.1 %) and glycerin (2%) was prepared the pH was adjusted to pH 7.65. Polyhexamethylene biquanide (PHMB) was added to half of this solution to yield a final concentration of 1 ppm. Another set of aqueous solutions containing hydrogen peroxide (60 ppm), Pluronic ® F127 (0.1%) and glycerin (2.3%) was prepared the pH was adjusted to pH 7.35. Polyhexamethylene biquanide (PHMB) was added to half of this solution to yield a final concentration of 1 ppm.
Each of these solutions were tested for their activity against S. aureus and C. albicans. The data are summarized in the following table.
S. aureus C. albicans
Formulation 4 hours 4 hours
No preservative 0.05 -0.09 PHMB 4.03 2.40
Hydrogen peroxide 1.95 1.06 Hydrogen peroxide, PHMB > 4.73 3.08
Marketed Product 1 * > 4.73 0.54 Marketed Product 2 ** > 4.73 2.57
* marketed product 1 having the general composition: A sterile isotonic aqueous solution containing sodium chloride, polyoxyethylene polyoxypropylene block copolymer, sodium phosphate dibasic, sodium phosphate monobasic, and preserved with edetate disodium dihydrate 0.025% and polyhexanide 0.0001%.
** marketed product 2 having the general composition: A sterile, isotonic solution that contains HYDRANATE®(hydroxyalkylphosphonate), boric acid, edetate disodium, poloxamine, sodium borate and sodium chloride; preserved with DYMED® (polyaminopropyl biquanide) 0.0001 %.
The results demonstrate the improved efficacy of the polyhexamethylene biquanide - hydrogen peroxide combination against S. aureus and C. albicans. The effectiveness was superior to that found in either commercially marketed products.
Example 2 PHMB - Peroxide
Formulations were prepared by dissolving L-histidine or Bis-Tris Propane in water. The pH of the solutions were adjusted to 7.3 with 1 N hydrochloric acid. Hydrogen peroxide, Dequest ® 2010 and polyhexamethylenebiguanide HCI (PHMB) were added to these solutions. The formulations were diluted to volume with water. Each of these solutions were tested for their activity against C. albicans (ATCC 10231 ) following a two hour exposure. The activity is expressed as a log reduction from the initial inoculum. The compositions, concentrations and activity of each of the solutions are summarized in the following table.
Log Preservative Buffer Hydrogen Dequest
Reduction Peroxide 2010
1.59 Bis-Tris Propane 0.2% none none 0.006%
2.05 Bis-Tris Propane 0.2% none 0.006% 0.006%
1.25 L-histdine 0.2% none none 0.006%
1.85 L-histdine 0.2% none 0.006% 0.006%
The results demonstrate the improved antifungal efficacy of the polyhexamethylene biguanide - hydrogen peroxide combination against C. albicans.
Example 3
PHMB -
Formulations were prepared by dissolving L-histidine, Bis-Tris Propane, or Tricine in water. The pH of the solutions were adjusted to 7.3 with 1 N hydrochloric acid. Glycerin, hydrogen peroxide, Dequest 2010 and polyhexamethylenebiguanide HCI (PHMB) were added to these solutions. The formulations were diluted to volume with water. Each of these solutions were tested for their activity against C. albicans (ATCC 10231 ) following a two hour exposure. The activity is expressed as a log reduction from the initial inoculum. The compositions, concentrations and activity of each of the solutions are summarized in the following table.
Log Preservative Buffer Glycerin Hydrogen Dequest Reduction Peroxide 2010
1.60 PHMB 0.0001 % L-Histidine 0.2% none none none 2.38 PHMB 0.0001 % L-Histidine 0.2% none 0.006% none
1.27 PHMB 0.0001 % L-Histidine 0.2% none none 0.006% 2.25 PHMB 0.0001% L-Histidine 0.2% none 0.006% 0.006%
1.08 PHMB 0.0001% L-Histidine 0.2% none none 0.003% 2.04 PHMB 0.0001% L-Histidine 0.2% none 0.006% 0.003%
1.57 PHMB 0.0001 % L-Histidine 0.2% 0.50% none none 2.15 PHMB 0.0001 % L-Histidine 0.2% 0.50% 0.006% none
1.25 PHMB 0.0001 % L-Histidine 0.2% 0.50% none 0.006% 2.04 PHMB 0.0001% L-Histidine 0.2% 0.50% 0.006% 0.006%
1.08 PHMB 0.0001% L-Histidine 0.2% 0.50% none 0.003% 1.93 PHMB 0.0001% L-Histidine 0.2% 0.50% 0.006% 0.003%
2.80 PHMB 0.0001% Bis-Tris Propane 0.2% none none none 3.69 PHMB 0.0001% Bis-Tris Propane 0.2% none 0.006% none
2.20 PHMB 0.0001% Bis-Tris Propane 0.2% none none 0.006% 3.18 PHMB 0.0001 % Bis-Tris Propane 0.2% none 0.006% 0.006%
2.18 PHMB 0.0001 % Bis-Tris Propane 0.2% none none 0.003% 3.05 PHMB 0.0001 % Bis-Tris Propane 0.2% none 0.006% 0.003%
2.78 PHMB 0.0001 % Bis-Tris Propane 0.2% 0.50% none none 3.32 PHMB 0.0001 % Bis-Tris Propane 0.2% 0.50% 0.006% none
2.29 PHMB 0.0001% Bis-Tris Propane 0.2% 0.50% none 0.006% 3.29 PHMB 0.0001% Bis-Tris Propane 0.2% 0.50% 0.006% 0.006%
2.13 PHMB 0.0001% Bis-Tris Propane 0.2% 0.50% none 0.003% 3.31 PHMB 0.0001 % Bis-Tris Propane 0.2% 0.50% 0.006% 0.003%
1.64 PHMB 0.0001 % Tricine 0.2% none none none 2.05 PHMB 0.0001 % Tricine 0.2% none 0.006% none
1.16 PHMB 0.0001 % Tricine 0.2% none none 0.006% 1.76 PHMB 0.0001% Tricine 0.2% none 0.006% 0.006%
1.17 PHMB 0.0001% Tricine 0.2% none none 0.003% 1.78 PHMB 0.0001% Tricine 0.2% none 0.006% 0.003%
The results demonstrate the improved antifungal against C. albicans in each paired formulation, when 0.006% hydrogen peroxide is added. The data demonstrates that the increased activity is independent on the presence of Dequest 2010.
Example 4
PHMB - Peroxide
Formulations were prepared by dissolving Tricine, Citiric Acid, Bicine, L- histidine.Glycine, or Lysine in water. The pH of the solutions were adjusted to 7.3 with 1 N hydrochloric acid. Hydrogen peroxide, Dequest ® 2010 and polyhexamethylenebiguanide HCI (PHMB) were added to these solutions. The formulations were diluted to volume with water. Each of these solutions were tested for their activity against C. albicans (ATCC 10231) following a two hour exposure. The activity is expressed as a log reduction from the initial inoculum. The compositions, concentrations and activity of each of the solutions are summarized in the following table.
Log Hydrogen Deques 2010 Reduction Preservative Buffer Peroxide
1.90 PHMB 0.0001 % Tricine 0.2% none none 2.09 PHMB 0.0001% Tricine 0.2% 0.006% 0.003%
0.25 PHMB 0.0001 % Citric Acid 0.2% none none
0.70 PHMB 0.0001 % Citric Acid 0.2% 0.006% 0.003%
2.01 PHMB 0.0001 % Bicine 0.2% none none
2.47 PHMB 0.0001 % Bicine 0.2% 0.006% 0.003%
2.01 PHMB 0.0001% Histidine 0.2% none none
2.42 PHMB 0.0001 % Histidine 0.2% 0.006% 0.003%
1.94 PHMB 0.0001 % Glycine 0.2% none none
2.89 PHMB 0.0001 % Glycine 0.2% 0.006% 0.003%
2.69 PHMB 0.0001 % Lysine 0.2% none none
2.84 PHMB 0.0001 % Lysine 0.2% 0.006% 0.003%
The results demonstrate the improved antifungal efficacy of the polyhexamethylene biguanide - hydrogen peroxide combination.
Example 5 PHMB - Peroxide
Formulations were prepared by dissolving Bis-Tris Propane, L-histidine, or Tricine in water. The pH of the solutions were adjusted to 7.3 with 1 N hydrochloric acid. The tonicity agent, hydrogen peroxide, Dequest 2010 and polyhexamethylenebiguanide HCI (PHMB) were added to these solutions. The formulations were diluted to volume with water. Each of these solutions were tested for their activity against C. albicans (ATCC 10231 ) following a two hour exposure. The activity is expressed as a log reduction from the initial inoculum. The compositions, concentrations and activity of each of the solutions are summarized in the following table.
Log Hydrogen Deques' Reduction Preservative Buffer Tonicity Agent Wetting Agent Peroxide 2010
3.85 PHMB 0.0001% Bis-Tris Propane none Cremophor RH 40 none none
0.2%
4.70 PHMB 0.0001% Bis-Tris Propane none Cremophor RH 40 0.006% 0.003%
0.2%
2.42 PHMB 0.0001% L-Histidine 0.2% none Cremophor RH 40 none none
3.34 PHMB 0.0001% L-Histidine 0.2% none Cremophor RH 40 0.006% 0.003%
2.17 PHMB 0.0001% Tricine none Cremophor RH 40 none none
2.69 PHMB 0.0001% Tricine none Cremophor RH 40 0.006% 0.003%
3.70 PHMB 0.0001% Bis-Tris Propane glycerin 3% Cremophor RH 40 none none 0.2%
4.40 PHMB 0.0001% Bis-Tris Propane glycerin 3% Cremophor RH 40 0.006% 0.003% 0.2%
2.19 PHMB 0.0001% L-Histidine 0.2% glycerin 3% Cremophor RH 40 none none
2.94 PHMB 0.0001% L-Histidine 0.2% glycerin 3% Cremophor RH 40 0.006% 0.003%
2.19 PHMB Tricine glycerin 3% Cremophor RH none none 0.0001% 40
2.45 PHMB 0.0001% Tricine glycerin 3% Cremophor RH 40 0.006% 0.003%
2.19 PHMB 0.0001% L-Histidine 0.2% propylene glycol Cremophor RH 40 none none 3%
2.95 PHMB 0.0001% L-Histidine 0.2% propylene glycol Cremophor RH 40 0.006% 0.003% 3%
4.40 PHMB 0.0001% Bis-Tris Propane sorbitol 5% Cremophor RH 40 none none 0.2%
4.70 PHMB 0.0001% Bis-Tris Propane sorbitol 5% Cremophor RH 40 0.006% 0.003% 0.2%
3.36 PHMB 0.0001 % L-Histidine 0.2% sorbitol 5% Cremophor RH 40 none none
3.92 PHMB 0.0001 % L-Histidine 0.2% sorbitol 5% Cremophor RH 40 0.006% 0.003%
2.54 PHMB 0.0001 % L-Histidine 0.2% inositol 5% Cremophor RH 40 none none
3.08 PHMB 0.0001 % L-Histidine 0.2% inositol 5% Cremophor RH 40 0.006% 0.003%
The data shows that the addition of 0.006% hydrogen peroxide to polyhexamethylene biguanide provides increased antifungal ctivity against C.
albicans. Consistent results were found in the presence of Cremophor RH40 with histidine, tricine, Bis-Tris Propane, glycerin, propylene glycol, and soribitol.
Claims (7)
1. An ophthalmic solution comprising 0.01 to 0.0001 percent by weight of a peroxide producing agent and 0.1 to 500 parts per million of a cationic, polymeric preservative.
2. The solution of claim 1 wherein said cationic, polymeric preservative represented by the chemical formula:
X1 — f-Z NH C NH C NH-Jn-Z X2
NH NH
wherein Z is an organic divalent bridging group which may be the same or different throughout the polymer, n is on average at least 3, and X1 and X2 are chosen from the group consisiting of:
3. The solution of Claim 1 where said peroxide source is chosen from the group consisting of hydrogen peroxide, sodium perborate decahydrate, sodium persulfate. sodium peroxide, urea peroxide and peracetic acid.
4. The solution of Claim 1 that further comprises 0.05 to 2.5 percent by weight of a buffer chosen from the group consisting of boric acid, sodium borate, potassium citrate, citric acid, sodium bicarbonate, TRIS, Na2HPO , NaH2PO4 and KH2PO4, and mixtures thereof.
5. The solution of Claim 4 that further comprises a surfactant.
6. A contact lens vial comprising: a vial; a contact-lens; and a sufficient amount of a solution to immerse said contact lens, wherein said solution comprises 0.01 to 0.0001 percent by weight of a peroxide producing agent and 0.1 to 500 ppm of a cationic, polymeric preservative.
7. The solution of Claim 4 wherein n is equal to on average 5 to 20
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24670800P | 2000-11-08 | 2000-11-08 | |
| US24668900P | 2000-11-08 | 2000-11-08 | |
| US24670900P | 2000-11-08 | 2000-11-08 | |
| US24670700P | 2000-11-08 | 2000-11-08 | |
| US60/246,707 | 2000-11-08 | ||
| US60/246,709 | 2000-11-08 | ||
| US60/246,708 | 2000-11-08 | ||
| US60/246,689 | 2000-11-08 | ||
| PCT/US2001/046882 WO2002040062A2 (en) | 2000-11-08 | 2001-11-08 | Improved ophthalmic and contact lens solutions with a peroxide source and a cationic polymeric preservative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002239545A1 true AU2002239545A1 (en) | 2002-08-01 |
| AU2002239545B2 AU2002239545B2 (en) | 2006-10-05 |
Family
ID=27500231
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002239545A Ceased AU2002239545B2 (en) | 2000-11-08 | 2001-11-08 | Improved ophthalmic and contact lens solutions with a peroxide source and a cationic polymeric preservative |
| AU3954502A Pending AU3954502A (en) | 2000-11-08 | 2001-11-08 | Improved ophthalmic and contact lens solutions with a peroxide source and a cationic polymeric preservative |
| AU2002251685A Ceased AU2002251685B8 (en) | 2000-11-08 | 2001-11-08 | Improved ophthalmic and contact lens solutions containing forms of vitamin B |
| AU2595002A Pending AU2595002A (en) | 2000-11-08 | 2001-11-08 | L-histidine in ophthalmic solutions |
| AU2002225950A Ceased AU2002225950B2 (en) | 2000-11-08 | 2001-11-08 | L-histidine in ophthalmic solutions |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU3954502A Pending AU3954502A (en) | 2000-11-08 | 2001-11-08 | Improved ophthalmic and contact lens solutions with a peroxide source and a cationic polymeric preservative |
| AU2002251685A Ceased AU2002251685B8 (en) | 2000-11-08 | 2001-11-08 | Improved ophthalmic and contact lens solutions containing forms of vitamin B |
| AU2595002A Pending AU2595002A (en) | 2000-11-08 | 2001-11-08 | L-histidine in ophthalmic solutions |
| AU2002225950A Ceased AU2002225950B2 (en) | 2000-11-08 | 2001-11-08 | L-histidine in ophthalmic solutions |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20060078626A1 (en) |
| EP (5) | EP3045168A1 (en) |
| JP (6) | JP2004525865A (en) |
| CN (3) | CN1212848C (en) |
| AT (3) | ATE405265T1 (en) |
| AU (5) | AU2002239545B2 (en) |
| CA (3) | CA2428994C (en) |
| CY (3) | CY1108439T1 (en) |
| DE (3) | DE60141039D1 (en) |
| DK (3) | DK1331902T3 (en) |
| ES (4) | ES2578679T3 (en) |
| PT (3) | PT1339414E (en) |
| WO (3) | WO2002038077A2 (en) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030129083A1 (en) * | 1997-11-26 | 2003-07-10 | Advanced Medical Optics, Inc. | Multi purpose contact lens care compositions including propylene glycol or glycerin |
| US9492582B2 (en) * | 2000-11-08 | 2016-11-15 | Fxs Ventures, Llc | Ophthalmic and contact lens solutions containing simple saccharides as preservative enhancers |
| US20070110782A1 (en) * | 2000-11-08 | 2007-05-17 | Fxs Ventures, Llc | L-histidine in ophthalmic solutions |
| US9308264B2 (en) | 2000-11-08 | 2016-04-12 | Fxs Ventures, Llc | Ophthalmic contact lens solutions containing forms of vitamin B |
| US20060127496A1 (en) * | 2000-11-08 | 2006-06-15 | Bioconcept Laboratories | L-histidine in ophthalmic solutions |
| US20070104744A1 (en) * | 2000-11-08 | 2007-05-10 | Fxs Ventures, Llc | Ophthalmic and contact lens solutions containing forms of vitamin b |
| US20070098813A1 (en) * | 2000-11-08 | 2007-05-03 | Fxs Ventures, Llc | Ophthalmic and contact lens solutions with a peroxide source and a preservative |
| CN1281283C (en) | 2001-01-09 | 2006-10-25 | 路易斯·约翰·瓦赫纳尔 | Procedure and composition of treatment and/or care of eye |
| US8541472B2 (en) | 2001-12-05 | 2013-09-24 | Aseptica, Inc. | Antiseptic compositions, methods and systems |
| JP4634024B2 (en) * | 2003-10-23 | 2011-02-16 | 株式会社シード | Contact lens solution |
| US20050214382A1 (en) | 2004-03-29 | 2005-09-29 | Erning Xia | Zinc preservative composition and method of use |
| DE602005018515D1 (en) * | 2004-10-01 | 2010-02-04 | Menicon Co Ltd | METHOD FOR STERILIZING PACKAGED CONTACT LENSES WITH PACKAGING SOLUTION |
| EP2754350A3 (en) * | 2005-10-25 | 2014-11-12 | Dow Global Technologies LLC | Antimicrobial composition and method |
| JP5068762B2 (en) * | 2005-11-16 | 2012-11-07 | ノバルティス アーゲー | Lens care solution |
| US20090092574A1 (en) * | 2006-12-29 | 2009-04-09 | Scott Richard W | Ophthalmic And Otic Compositions Of Facially Amphiphilic Polymers And Oligomers And Uses Thereof |
| US8278309B2 (en) | 2008-10-27 | 2012-10-02 | Polymedix, Inc. | Synthetic mimetics of host defense and uses thereof |
| JP2013516470A (en) * | 2010-01-07 | 2013-05-13 | ポリメディックス・インコーポレーテッド | Anti-heparin compounds |
| RU2450515C1 (en) * | 2010-12-01 | 2012-05-20 | Федеральное государственное учреждение "Межотраслевой научно-технический комплекс "Микрохирургия глаза" имени академика С.Н. Федорова Федерального агентства по высокотехнологичной медицинской помощи" | Preserving agent for donor cornea |
| US20130264213A1 (en) * | 2010-12-21 | 2013-10-10 | Basf Se | Composition for metal electroplating comprising leveling agent |
| TWI480039B (en) * | 2011-03-10 | 2015-04-11 | Pegavision Corp | Aqueous composition for contact lens |
| JP5833745B2 (en) | 2011-05-16 | 2015-12-16 | セルシューティクス・コーポレーション | Compounds for use in the treatment of mucositis |
| DE102012014581A1 (en) * | 2012-07-24 | 2014-01-30 | Azoba Health Care Ag | vitamin preparation |
| JP6413658B2 (en) * | 2014-01-08 | 2018-10-31 | 日油株式会社 | Eye drops |
| CN105168221A (en) * | 2015-10-14 | 2015-12-23 | 康普药业股份有限公司 | Medicine composition for treating beriberi |
| TWI634205B (en) * | 2016-06-27 | 2018-09-01 | 晶碩光學股份有限公司 | Solution for treating contact lens |
| EP3552601A1 (en) | 2018-04-11 | 2019-10-16 | Karl Bodenschatz | Pharmaceutical composition containing dexpanthenol and polihexanide |
| CN109381480B (en) * | 2018-11-15 | 2021-02-09 | 江苏聚锦生物医疗科技有限责任公司 | Compound polyhexamethylene biguanide disinfectant and preparation method thereof |
| WO2021248008A1 (en) | 2020-06-05 | 2021-12-09 | Innovation Pharmaceuticals Inc. | Arylamide compounds for treatment and prevention of viral infections |
Family Cites Families (120)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US482689A (en) * | 1892-09-13 | James mcdermott | ||
| US2976576A (en) * | 1956-04-24 | 1961-03-28 | Wichterle Otto | Process for producing shaped articles from three-dimensional hydrophilic high polymers |
| US3429576A (en) * | 1965-08-28 | 1969-02-25 | Yoshiaki Ikeda | Golf club having level indicating means and weight means |
| US3503393A (en) * | 1966-05-19 | 1970-03-31 | Blease Anaesthetic Equip Ltd | Patient controlled respiratory apparatus |
| DE1667942B2 (en) * | 1967-03-15 | 1977-05-12 | Ceskoslovenska Akademie Ved, Prag | METHOD AND DEVICE FOR STERILE STORAGE OF OBJECTS FROM SWELLED HYDOGELS, IN PARTICULAR OF CONTACT LENSES |
| US3689673A (en) * | 1970-11-10 | 1972-09-05 | Barnes Hind Pharm Inc | The process of soaking and sterilizing hydrophilic soft contact lenses with chlorhexidene |
| US3755561A (en) * | 1971-03-22 | 1973-08-28 | Burton Parsons & Co Inc | Bactericidal contact lens solution |
| FR2199470B1 (en) * | 1971-06-21 | 1977-12-30 | Wave Energy Systems | |
| US4022834A (en) * | 1972-03-16 | 1977-05-10 | A/S Farmaceutisk Industri | Antibacterially active hexamethylene-bis-biguanides |
| US3888782A (en) * | 1972-05-08 | 1975-06-10 | Allergan Pharma | Soft contact lens preserving solution |
| US3876768A (en) * | 1972-11-06 | 1975-04-08 | Hydrophilics Int Inc | Sterilization of soft, hydrophilic acrylate and methacrylate copolymer materials |
| US3911107A (en) * | 1972-12-18 | 1975-10-07 | Flow Pharma Inc | Iodine composition and dissipating solution |
| US3910296A (en) * | 1973-04-20 | 1975-10-07 | Allergan Pharma | Method of removing proteinaceous deposits from contact lenses |
| US3943251A (en) * | 1973-06-27 | 1976-03-09 | Medow Norman B | Ophthamological use of hydrastis compounds |
| US4029817A (en) * | 1973-09-24 | 1977-06-14 | Allergan Pharmaceuticals | Soft contact lens preserving solutions |
| GB1562899A (en) * | 1975-06-17 | 1980-03-19 | Wellcome Found | Pharmaceutical compositions containing substituted 9-( -d-arabnofuranosyl)purine-5'-phosphate and salts thereof |
| US4046706A (en) * | 1976-04-06 | 1977-09-06 | Flow Pharmaceuticals, Inc. | Contact lens cleaning composition |
| IT1063325B (en) * | 1976-05-19 | 1985-02-11 | Brevitex Ets Exploit | DEVICE FOR SPREADING THE CROSSBODY FRAMES |
| US4136173A (en) * | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Mixed xanthan gum and locust beam gum therapeutic compositions |
| US4209817A (en) * | 1978-03-15 | 1980-06-24 | Square D Company | Circuit breaker having an electronic fault sensing and trip initiating unit |
| US4394381A (en) * | 1979-04-13 | 1983-07-19 | George F. And Irene Sherrill 1978 Trust No. 1 | Method for the relief of pain |
| US4361549A (en) * | 1979-04-26 | 1982-11-30 | Ortho Pharmaceutical Corporation | Complement-fixing monoclonal antibody to human T cells, and methods of preparing same |
| JPS599600B2 (en) * | 1980-11-14 | 1984-03-03 | 花王株式会社 | Shampoo - Composition |
| US4361548A (en) * | 1980-11-28 | 1982-11-30 | Bausch & Lomb Incorporated | Contact lens disinfecting and preserving solution (polymeric) |
| US4361458A (en) * | 1981-02-13 | 1982-11-30 | The Wurlitzer Company | Piano soundboard and method of making same |
| US4354952A (en) * | 1981-03-12 | 1982-10-19 | Bausch & Lomb Incorporated | Contact lens disinfecting and preserving solution comprising chlorhexidine and salts thereof |
| US4525346A (en) * | 1981-09-28 | 1985-06-25 | Alcon Laboratories, Inc. | Aqueous antimicrobial ophthalmic solutions |
| US4820352A (en) * | 1983-01-10 | 1989-04-11 | Bausch & Lomb Incorporated | Cleaning and conditioning solutions for contact lenses and methods of use |
| JPS6038323A (en) * | 1983-08-10 | 1985-02-27 | Sankyo Co Ltd | Ophthalmic anti-inflammatory agent |
| US4758595A (en) * | 1984-12-11 | 1988-07-19 | Bausch & Lomb Incorporated | Disinfecting and preserving systems and methods of use |
| US4836986A (en) * | 1984-09-28 | 1989-06-06 | Bausch & Lomb Incorporated | Disinfecting and preserving systems and methods of use |
| US4748189A (en) * | 1985-04-19 | 1988-05-31 | Ciba-Geigy Corporation | Ophthalmic solutions and methods for improving the comfort and safety of contact lenses |
| USRE32672E (en) * | 1985-09-09 | 1988-05-24 | Allergan, Inc. | Method for simultaneously cleaning and disinfecting contact lenses using a mixture of peroxide and proteolytic enzyme |
| JPH0672866B2 (en) * | 1986-03-19 | 1994-09-14 | 本田技研工業株式会社 | Oxygen concentration detector |
| US4863900A (en) * | 1987-01-15 | 1989-09-05 | The Research Foundation Of State University Of New York | Method for reducing viral transmission with poly-L-histidine |
| US4783488A (en) * | 1987-01-31 | 1988-11-08 | Bausch & Lomb Incorporated | Contact lens wetting solution |
| US5246708A (en) * | 1987-10-28 | 1993-09-21 | Pro-Neuron, Inc. | Methods for promoting wound healing with deoxyribonucleosides |
| US5624958A (en) * | 1987-12-31 | 1997-04-29 | Isaacs; Charles E. | Disinfecting contact lenses |
| US5192535A (en) * | 1988-02-08 | 1993-03-09 | Insite Vision Incorporated | Ophthalmic suspensions |
| JPH01211595A (en) * | 1988-02-18 | 1989-08-24 | Kikkoman Corp | Novel n-acetyl-beta-d-glucosamine derivative, production thereof and utilization thereof to reagent for measuring n-acetyl-beta-d-glucosamidase activity |
| SG64856A1 (en) * | 1988-08-04 | 1999-05-25 | Novartis Ag | A method of preserving ophthalimic solutions and composition thereof |
| US5607698A (en) * | 1988-08-04 | 1997-03-04 | Ciba-Geigy Corporation | Method of preserving ophthalmic solution and compositions therefor |
| US5089261A (en) * | 1989-01-23 | 1992-02-18 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US5182258A (en) * | 1989-03-20 | 1993-01-26 | Orbon Corporation | Systemic delivery of polypeptides through the eye |
| US4891423A (en) * | 1989-03-20 | 1990-01-02 | Stockel Richard F | Polymeric biguanides |
| US5175161A (en) * | 1989-04-06 | 1992-12-29 | Sankyo Company, Limited | Occular hypotensive agents |
| JP2893537B2 (en) * | 1989-07-20 | 1999-05-24 | 東海電化工業株式会社 | Histidine-hydrogen peroxide adduct and method for producing the same |
| US4988710A (en) * | 1989-08-25 | 1991-01-29 | Washington University | Aryl-cycloalkyl-alkanolamines for treatment of cholinergic neurotoxins |
| US5078908A (en) * | 1989-10-02 | 1992-01-07 | Allergan, Inc. | Methods for generating chlorine dioxide and compositions for disinfecting |
| US4997626A (en) * | 1990-01-05 | 1991-03-05 | Allergan, Inc. | Methods to disinfect contact lenses |
| US5279673A (en) * | 1990-01-05 | 1994-01-18 | Allergan, Inc. | Methods to disinfect contact lenses |
| US5300296A (en) * | 1989-11-06 | 1994-04-05 | Frank J. Holly | Antimicrobial agent for opthalmic formulations |
| GB9002422D0 (en) * | 1990-02-03 | 1990-04-04 | Boots Co Plc | Anti-microbial compositions |
| US5174872A (en) * | 1990-06-08 | 1992-12-29 | Technicon Instruments Corporation | Metal-free buffer for ion selective electrode-based assays |
| US5422073A (en) * | 1990-12-27 | 1995-06-06 | Allergan, Inc. | Method and composition for disinfecting contact lenses |
| JPH04226666A (en) * | 1990-12-29 | 1992-08-17 | Tome Sangyo Kk | Method for disinfecting and cleaning contact lens |
| US5460808A (en) | 1991-05-15 | 1995-10-24 | Chanel, Inc. | Mascara composition |
| US5523012A (en) * | 1991-07-19 | 1996-06-04 | Ciba-Geigy Corporation | Hydrogen peroxide disinfection solutions |
| NZ243749A (en) * | 1991-08-30 | 1994-11-25 | Allergan Inc | Composition for neutralising and indicating the absence of peroxide comprising a neutralising compound and vitamin b-12 |
| US5439572A (en) * | 1991-12-02 | 1995-08-08 | Isoclear, Inc. | Lens protective encasement packet |
| EP0690728B1 (en) * | 1993-01-07 | 1998-11-25 | Polymer Technology Corporation | Preservative system for contact lens solutions |
| AU6363694A (en) * | 1993-03-18 | 1994-10-11 | Polymer Technology Corporation | Alcohol-containing abrasive composition for cleaning contact lenses |
| DE4345199C2 (en) * | 1993-05-22 | 1995-10-12 | Asta Medica Ag | Use of dihydrolipoic acid to suppress intolerance reactions in the border area of implants with living body tissue |
| ES2122288T3 (en) * | 1993-05-26 | 1998-12-16 | Fresenius Ag | ANTI-INFECTIOUS. |
| US5968904A (en) * | 1993-06-04 | 1999-10-19 | Demegen, Inc. | Modified arginine containing lytic peptides and method of making the same by glyoxylation |
| US5561107A (en) * | 1993-06-04 | 1996-10-01 | Demeter Biotechnologies, Ltd. | Method of enhancing wound healing by stimulating fibroblast and keratinocyte growth in vivo, utilizing amphipathic peptides |
| IL109762A0 (en) | 1993-06-18 | 1994-08-26 | Allergan Inc | Method for treating hypoxia-associated ocular complications |
| US5661130A (en) * | 1993-06-24 | 1997-08-26 | The Uab Research Foundation | Absorption enhancers for drug administration |
| US5449658A (en) * | 1993-12-07 | 1995-09-12 | Zeneca, Inc. | Biocidal compositions comprising polyhexamethylene biguanide and EDTA, and methods for treating commercial and recreational water |
| US5591773A (en) * | 1994-03-14 | 1997-01-07 | The Trustees Of Columbia University In The City Of New York | Inhibition of cataract formation, diseases resulting from oxidative stress, and HIV replication by caffeic acid esters |
| US5361287A (en) * | 1994-03-29 | 1994-11-01 | B&W Fuel Company | Nuclear fuel assembly lower end fitting |
| NZ283658A (en) * | 1994-04-04 | 1999-09-29 | William R Freeman | Compositions and treatment of increased intraocular pressure with phosphonyl-alkyloxy-pyrimidines/purines (nucleosides) |
| US5674450A (en) * | 1994-04-28 | 1997-10-07 | Johnson & Johnson Medical, Inc. | Vapor sterilization using a non-aqueous source of hydrogen peroxide |
| US5547990A (en) * | 1994-05-20 | 1996-08-20 | Lonza, Inc. | Disinfectants and sanitizers with reduced eye irritation potential |
| US5494937A (en) * | 1994-07-22 | 1996-02-27 | Alcon Laboratories, Inc. | Saline solution for treating contact lenses |
| AU3070395A (en) * | 1994-07-22 | 1996-02-22 | Alcon Laboratories, Inc. | Use of low molecular weight amino acids in ophthalmic compositions |
| US5849291A (en) * | 1994-10-17 | 1998-12-15 | Symbollon Corporation | Opthalmic non-irritating iodine medicament |
| CA2160962C (en) * | 1994-10-20 | 2009-12-29 | Junya Inoue | Reagent for analyzing solid components in urine and method for analyzing solid components by employing the same |
| JP3968131B2 (en) * | 1994-11-28 | 2007-08-29 | サンスター株式会社 | Antibacterial preparation |
| JP3442168B2 (en) * | 1994-11-30 | 2003-09-02 | 旭化成アイミー株式会社 | Care products |
| US6024954A (en) * | 1994-12-12 | 2000-02-15 | Allergan | Compositions and methods for disinfecting contact lenses and preserving contact lens care products |
| US5739178A (en) * | 1995-05-15 | 1998-04-14 | Allergan | Polymer, article and method for inhibiting the growth of ocular pathogens in eye care products |
| US5611464A (en) * | 1995-05-30 | 1997-03-18 | Ciba Geigy Corporation | Container for preserving media in the tip of a solution dispenser |
| US5718895A (en) * | 1995-11-16 | 1998-02-17 | Alcon Laboratories, Inc. | Enzymes with low isoelectric points for use in contact lens cleaning |
| US5780450A (en) * | 1995-11-21 | 1998-07-14 | Alcon Laboratories, Inc. | Use of adenosine uptake inhibitors for treating retinal or optic nerve head damage |
| US5965736A (en) * | 1996-01-16 | 1999-10-12 | Lumigen, Inc. | Compositions and methods for generating red chemiluminescence |
| ES2210404T3 (en) * | 1996-01-22 | 2004-07-01 | BAUSCH & LOMB INCORPORATED | DOUBLE NEUTRALIZATION SYSTEM FOR TREATMENT WITH IODINE OF CONTACT LENSES. |
| EP0880356A4 (en) * | 1996-02-16 | 2002-03-27 | Univ California | Antimicrobial peptides and methods of use |
| AR006274A1 (en) * | 1996-03-18 | 1999-08-11 | Bio Lab Inc | PRE-MIXED COMPOSITION FOR RINSING WATER, METHODS FOR RINSING WATER AND METHOD FOR INCREASING THE USEFUL LIFE OF HYDROGEN PEROXIDE IN POOL WATER. |
| US6358897B1 (en) * | 1996-06-07 | 2002-03-19 | Alcon Laboratories, Inc. | Alkyl trypsin compositions and methods of use in contact lens cleaning and disinfecting systems |
| US5719110A (en) * | 1996-08-14 | 1998-02-17 | Allergan | Contact lens care compositions with inositol phosphate components |
| JP3829380B2 (en) * | 1996-12-18 | 2006-10-04 | 住友化学株式会社 | Pest repellent and pest repellent method |
| US5952320A (en) * | 1997-01-07 | 1999-09-14 | Abbott Laboratories | Macrocyclic inhibitors of matrix metalloproteinases and TNFα secretion |
| US5945446A (en) * | 1997-02-10 | 1999-08-31 | Laubc Biochemicals, Corporation | Process for preparing synthetic soil-extract materials and medicaments based thereon |
| US6022732A (en) * | 1997-04-09 | 2000-02-08 | Allergan | Hydrogen peroxide destroying compositions and methods of using same |
| RU2127100C1 (en) * | 1997-04-17 | 1999-03-10 | Борзенок Сергей Анатольевич | Ocular drops "pyrotonik" |
| US5811446A (en) * | 1997-04-18 | 1998-09-22 | Cytos Pharmaceuticals Llc | Prophylactic and therapeutic methods for ocular degenerative diseases and inflammations and histidine compositions therefor |
| US5925320A (en) * | 1997-06-04 | 1999-07-20 | Jones; John P. | Air purification system |
| JPH11137649A (en) * | 1997-11-10 | 1999-05-25 | Tomey Technology Kk | Method for cleaning and disinfecting contact lens |
| ID24946A (en) * | 1997-11-12 | 2000-08-31 | Bausch & Lomb | CONTACT LENS TREATMENT WITH WATER SOLUTION CONSIST OF ALKALI CARBONAT |
| US6056920A (en) * | 1997-12-12 | 2000-05-02 | Vertex Pharmaceuticals Incorporated | Process for identifying a solvent condition suitable for determining a biophysical property of a protein |
| JPH11249087A (en) * | 1997-12-18 | 1999-09-17 | Tome:Kk | Light agent for contact lens |
| JPH11189533A (en) * | 1997-12-25 | 1999-07-13 | Taisho Pharmaceut Co Ltd | Eye drop |
| JP4065591B2 (en) * | 1998-01-07 | 2008-03-26 | Ｈｏｙａヘルスケア株式会社 | Contact lens solution and contact lens cleaning method using the same |
| US6156563A (en) * | 1998-01-29 | 2000-12-05 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Method for clarifying cane sugar juice |
| JP3883739B2 (en) * | 1998-05-22 | 2007-02-21 | 株式会社メニコン | Contact lens bactericidal solution |
| US6117869A (en) * | 1998-08-04 | 2000-09-12 | Warner-Lambert Company | Compounds for and methods of inhibiting matrix metalloproteinases |
| US6162393A (en) * | 1998-08-06 | 2000-12-19 | Ndt, Inc. | Contact lens and ophthalmic solutions |
| KR20010031258A (en) * | 1998-08-21 | 2001-04-16 | 요시다 쇼지 | Compositions for contact lenses |
| US6309596B1 (en) * | 1998-12-15 | 2001-10-30 | Bausch & Lomb Incorporated | Treatment of contact lenses with aqueous solution comprising a biguanide disinfectant stabilized by a poloxamine |
| JP2000347142A (en) * | 1999-06-02 | 2000-12-15 | Tomey Corp | Cleaning and preserving liquid agent for contact lens |
| US7678836B2 (en) * | 1999-11-04 | 2010-03-16 | Fxs Ventures, Llc | Method for rendering a contact lens wettable |
| JP2001302518A (en) * | 2000-02-15 | 2001-10-31 | Rohto Pharmaceut Co Ltd | Method for improving action and agent for improving action |
| JP2002104971A (en) * | 2000-09-27 | 2002-04-10 | Lion Corp | Ophthalmic composition |
| CN1468107A (en) * | 2000-10-03 | 2004-01-14 | 千寿制药株式会社 | Eye drops |
| US8557868B2 (en) * | 2000-11-04 | 2013-10-15 | Fxs Ventures, Llc | Ophthalmic and contact lens solutions using low molecular weight amines |
| AR034200A1 (en) * | 2001-01-12 | 2004-02-04 | Novartis Ag | AGENT FOR THE CARE OF CONTACT LENSES, ITS USE, AND CLEANING PROCEDURE |
| US6550862B2 (en) * | 2001-06-14 | 2003-04-22 | Cosco Management, Inc. | Juvenile vehicle seat cup holder |
| US6624203B1 (en) * | 2001-11-08 | 2003-09-23 | Francis X. Smith | Nucleic acid bases used in ophthalmic solutions |
| US6617291B1 (en) * | 2001-11-08 | 2003-09-09 | Francis X. Smith | Ophthalmic and contact lens solutions |
-
2001
- 2001-11-08 AU AU2002239545A patent/AU2002239545B2/en not_active Ceased
- 2001-11-08 DK DK01999161T patent/DK1331902T3/en active
- 2001-11-08 DK DK01993437.1T patent/DK1339414T3/en active
- 2001-11-08 CN CNB018218164A patent/CN1212848C/en not_active Expired - Fee Related
- 2001-11-08 JP JP2002542434A patent/JP2004525865A/en active Pending
- 2001-11-08 ES ES08014693.9T patent/ES2578679T3/en not_active Expired - Lifetime
- 2001-11-08 CN CNB01821813XA patent/CN1212847C/en not_active Expired - Fee Related
- 2001-11-08 WO PCT/US2001/046762 patent/WO2002038077A2/en active Application Filing
- 2001-11-08 DE DE60141039T patent/DE60141039D1/en not_active Expired - Lifetime
- 2001-11-08 EP EP16155318.5A patent/EP3045168A1/en not_active Withdrawn
- 2001-11-08 ES ES01993437T patent/ES2337446T3/en not_active Expired - Lifetime
- 2001-11-08 AT AT01999161T patent/ATE405265T1/en active
- 2001-11-08 CN CNB018218148A patent/CN1263463C/en not_active Expired - Fee Related
- 2001-11-08 PT PT01993437T patent/PT1339414E/en unknown
- 2001-11-08 EP EP01993437A patent/EP1339414B1/en not_active Expired - Lifetime
- 2001-11-08 JP JP2002540667A patent/JP4580143B2/en not_active Expired - Fee Related
- 2001-11-08 ES ES01999161T patent/ES2311035T3/en not_active Expired - Lifetime
- 2001-11-08 CA CA2428994A patent/CA2428994C/en not_active Expired - Lifetime
- 2001-11-08 CA CA2434961A patent/CA2434961C/en not_active Expired - Lifetime
- 2001-11-08 JP JP2002562269A patent/JP5258139B2/en not_active Expired - Fee Related
- 2001-11-08 ES ES01987313T patent/ES2311555T3/en not_active Expired - Lifetime
- 2001-11-08 DK DK01987313T patent/DK1337262T3/en active
- 2001-11-08 WO PCT/US2001/046841 patent/WO2002062260A2/en active Application Filing
- 2001-11-08 PT PT01987313T patent/PT1337262E/en unknown
- 2001-11-08 WO PCT/US2001/046882 patent/WO2002040062A2/en active Application Filing
- 2001-11-08 AU AU3954502A patent/AU3954502A/en active Pending
- 2001-11-08 EP EP08014693.9A patent/EP1992340B1/en not_active Expired - Lifetime
- 2001-11-08 EP EP01999161A patent/EP1331902B1/en not_active Expired - Lifetime
- 2001-11-08 EP EP01987313A patent/EP1337262B1/en not_active Expired - Lifetime
- 2001-11-08 AU AU2002251685A patent/AU2002251685B8/en not_active Ceased
- 2001-11-08 CA CA002428997A patent/CA2428997A1/en not_active Abandoned
- 2001-11-08 AU AU2595002A patent/AU2595002A/en active Pending
- 2001-11-08 AU AU2002225950A patent/AU2002225950B2/en not_active Ceased
- 2001-11-08 DE DE60135572T patent/DE60135572D1/en not_active Expired - Lifetime
- 2001-11-08 PT PT01999161T patent/PT1331902E/en unknown
- 2001-11-08 AT AT01987313T patent/ATE406167T1/en active
- 2001-11-08 US US10/544,149 patent/US20060078626A1/en not_active Abandoned
- 2001-11-08 AT AT01993437T patent/ATE454157T1/en active
- 2001-11-08 DE DE60135478T patent/DE60135478D1/en not_active Expired - Lifetime
-
2008
- 2008-10-23 CY CY20081101189T patent/CY1108439T1/en unknown
- 2008-10-23 CY CY20081101188T patent/CY1108438T1/en unknown
-
2010
- 2010-01-21 CY CY20101100066T patent/CY1110596T1/en unknown
- 2010-05-27 JP JP2010121081A patent/JP5301498B2/en not_active Expired - Fee Related
-
2013
- 2013-01-24 JP JP2013010972A patent/JP5868338B2/en not_active Expired - Fee Related
-
2015
- 2015-10-13 JP JP2015201977A patent/JP5923211B2/en not_active Expired - Lifetime
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