CA2098472C - Contact lens care product for hard and soft contact lenses - Google Patents
Contact lens care product for hard and soft contact lenses Download PDFInfo
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- CA2098472C CA2098472C CA 2098472 CA2098472A CA2098472C CA 2098472 C CA2098472 C CA 2098472C CA 2098472 CA2098472 CA 2098472 CA 2098472 A CA2098472 A CA 2098472A CA 2098472 C CA2098472 C CA 2098472C
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Abstract
The present invention relates to contact lens care products comprising an aminopropyl biguanide or a salt thereof, especially a compound of formula I
(see formula I) wherein n is an integer from 1 to 500, or a salt thereof, and the so-called tris buffer (trometamol) or a homolog thereof leaving up to 10 carbon atoms or a salt thereof. The invention relates also to the use of such a contact lens care product for cleaning and disin-fecting contact lenses.
(see formula I) wherein n is an integer from 1 to 500, or a salt thereof, and the so-called tris buffer (trometamol) or a homolog thereof leaving up to 10 carbon atoms or a salt thereof. The invention relates also to the use of such a contact lens care product for cleaning and disin-fecting contact lenses.
Description
Contact lens care product for hard and soft contact lenses The present invention relates to a contact lens care product for hard and soft contact lenses, comprising a (poly)aminopropyl biguanide and a special buffer.
Contact lens care products comprising an aminopropyl biguanide are already known. For 'example, GB 1432 345 describes ophthalmic compositions and compositions for disin-fecting contact lenses comprising an ophthalmologically acceptable polymeric biguanide.
Only phosphate buffers are disclosed as suitable buffers in that context.
EP-A1-180 309 also discloses.disinfecting and preserving solutions for contact lenses, comprising a biguanide and a buffer. The biguanide is again of the aminopropyl biguanide type. As buffer especially borate buffers are proposed. Additional buffers mentioned are citrate buffers, bicarbonate buffers and mixed phosphate buffers.
In contrast, the present invention relates to contact lens care products comprising an aminopropyl biguanide or a salt thereof and as buffer the so-called tris buffer (trometamol) or a homolog thereof having up to 10 carbon atoms or a salt thereof. The invention relates also to the use of such a contact lens care product for cleaning and disinfecting contact lenses.
-1a-According to one aspect of the present invention, there is provided a contact lens care product comprising an aminopropyl biguanide of formula NH NH
HzN-(CHz)3 (CHz)3-N-C-N-C-N-(CHz)3 (CHz)3-NHz H H H n (I) or a salt thereof and as buffer from 0.05 to less than 1.2 percent by weight of a compound of formula (CHz) y OH
to H~ (CHz)X-i-NHz (CHz) Z OH
(III) or a salt thereof, wherein n is an integer from 1 to 500, x, y and z are each independently of the others an integer, at least 1, and the sum of x, y and z is from 3 to 9.
The aminopropyl biguanides to be used according to the invention are especially those of formula I
NH NH
HzN- (CHz) 3 (CHz) 3 -H -C-H-C-H-(CHz) 3 n (CHz) 3' NHz (I) wherein n is an integer from 1 to 500; it is also possible to use salts of compounds of formula I, especially ophthalmologically acceptable salts thereof.
The compounds of formula I are known. Their preparation is described, for example, in C~B 702 268 and GB 1 152 24?.. In addition, those compounds are also commercially available, for example as Vant~xil~, Cosmocil~ or as Arlagard~E from ICI
Chemicals.
Depending on the manner in which they have been prepared, the compounds of formula I
rnay comprise certain amounts of a secondary product of formula II
NH NH
H2N-(CH2)3~H2)3-NH-C-rTH-~-NH-(CH2)~(CH2)3-NH-C-NH-CN (II) -J n o:r salts thereof, wherein n is likewise an integer from 1 to 500. Mixtures of compounds of formula I with those of formuhr II can likewise be used according to the invention. The proportion of compounds of formula II, based on the total amount of compounds of formula I and compounds of formula II., is preferably less than 20 percent by weight, more preferably less than from 2 to 10 percent by weight and is especially preferably zero percent by weight.
The index n in formulae I and lI is preff;rably from 1 to 200, especially from 2 to 100, more especially from 2 to 50 arid most especially from 3 to 12. Depending on the value of the index n in formula I or II, the molecular weight of the aminopropyl biguanides that can be: used is as low as the molecular weight of the monomer of formula I (n =
1), or in the raurge of approximately 600 to 1600 if oligomers are used, i.e. when n is, for example, from 3 to 8, or alternatively in the range of from approximately 50 000 to approximately 90 0100 if n is significantly higher, for e;cample approximately 270 to 500.
In the contact lens care products according to the invention, the compound of formula I is used preferably in an amount, based on the total amount of the contact lens care product, which is advantageously formulated as .an aqueous solution, of from 0.1 to 100 ppm (0.00001 - 0.01 percent by weight), especially in an amount of from 0.5 to 50 ppm (Ci.OC1005 - 0.005 percent by weight) and more especially in an amount of from 1 to ppm (0.0001 - 0.001 percenr. by weight), for example 1, 2 or 5 ppm.
S~rlts of compounds of formula I and formula II that are suitable within the scope of the present invention are water-soluble salts that are advantageously ophthalmologically acceptable. Suitable salts are those with inorganic or organic acids, for example hydro-chlorides, hydrobromides, borates, acetates, gluconates, sulfonates, maleates, ascorbates, 2Q~84'~2 _3_ tartrates or citrates.
T'he trometamol and its homologs having up to 10, preferably from 5 to 7, carbon atoms used according to the invention preferably are the compounds of formula III
( i H2 Iy-OH
HO-(CH2)X-C-NH2 (III) (CH2 )Z OH
v~~herein x, y and z are each independently of the others an integer, at least 1, and the sum of x, y and z is from 3 to 9, preferably from 3 to 6, or a salt thereof.
Special preference is given to 2-amino-2-hydroxymethyl-1,3-propanediol (trometamol), which corresponds to a compound of formula III wherein each of x and y and z is 1. The compound trometamol is a:~so referred to as tris buffer.
Trometamol and its homologs leaving up to 10 carbon atoms are already known.
Their use in medicaments for the treatment of inf7,ammations of the eye has already been disclosed in EP-A2-242 328. Compositions for the disinfection of contact lenses, comprising 1.2 tromethamine/tromethamine hydrochloride and 1 ppm polyhexamethylene biguanide hydrochloride, are already kno~,vn from WO 92/11876. Compounds of formula III
are, rr,,oreover, also commercially available.
The amount of trometamol used as buffer in the contact lens care products according to the invention, based on the total amount of the contact lens care product, is preferably from 0.05 to 5 percent by weiglht, preferably from 0.1 to 2.5 percent by weight and especially preferably from approximately 0.2 to approximately 1.5 percent by weight. The amount of trometamol used as huffer in the contact lens care products according to the invention, based on the total amount of the contact lens care product, is more especially from 0.05 to less than 1.2 percent by weight or from 0.05 to less than 0.8 percent by weight, very especially from 0.1 to 0.6 percent by weight, especially from 0.1 to less than 0.6 percent by weight, for example up to 0.5 percent by weight.
2-Amino-2-hydroxymethyl-1,3-propane.diol or a homolog thereof having up to 10 carbon atoms, or a salt thereof, can be used alone as buffer. Alternatively, one of the above-mentioned compounds can be used together with a salt thereof. Again, preference is given 20984'2 here to the use of ophthalmolo;gically acceptable salts, such as the salts mentioned above in connection with compounds of formula I. Especially suitable are the hydrochlorides or maleates of compounds of formula III, i.e., for example, a combination of 2-amino-2-hydroxymethyl-1,3-propanediol with the hydrochloride of 2-amino-2-hydroxymethyl-1,3-propanediol, or a combination of 2-amino-2-hydroxymethyl-1,3-propanediol with the maleate of 2-amino-2-hydroxymethyl-1,3-propanediol or 2-amino-2-hydroxymethyl-1,3-propanediol, to which smaa.l amounts of hydrochloric acid are added.
T'he contact lens care products according to the invention preferably do not comprise buffers other than compounds of formula III. They may, however, comprise other buffers in addition to one or more compounds of formula III.
The contact lens care products according to the invention are preferably formulated in such a manner that they are isotonic wish lachrymal fluid. They may in general comprise additives that are customary fo:r contact lens care products. Those include, for example, compounds that influence tonicity, surface-active compounds, compounds that influence viscosity, or complex formers. The contact lens care products according to the invention comprise those or other customary additives in amounts that vary within the range of the values familiar to the person skilled in the art.
A. solution that is isotonic with lachrymal fluid is generally understood to be a solution the concentration of which corresponds to the concentration of a 0.9 % sodium chloride solution. Departures therefrom are entirely possible, provided that the contact lenses to be treated are not damaged thereby. Isotonicity with lachrymal fluid or a different desired tonicity can be established by t:he addition of organic or inorganic compounds that influence tonicity. The former can be used, for example, in amounts of approximately 1 to 4.5 percent by weight, the latter in amounts of approximately 0.1 to 1.3 percent by weight.
In general, the amount of the compound that influences tonicity that is added is such that the tonicity of the composition according to the invention is especially in the range of from 200 to 450 milliosmols, preferably in the range of from approximately 270 to approximately 330 milliosmols. Typical organic compounds of that type are, for example, glycerol, urea, propylene glycol or sugars, such as mannitol or sorbitol, and typical inorganic compounds of that type are especially potassium chloride and sodium chloride.
Mixtures of those compounds with one another can also be used according to the invention.
Suitable surface-active compounds are mentioned, for example, in EP-A2-180 309.
Examples of especially suitable representatives that can be used according to the invention are poloxamer types and miranol types,. Other representatives are known to a person skilled in the art. Those compounds can be used, for example, in amounts of up to 20 percent by weight, espe:ciahly in amounts of from 0.4 to 5 percent by weight.
Suitable compounds that influence viscosity are also known to a person skilled in the art.
Examples of especially suitabhe representatives that can be used according to the invention are polyvinyl alcohol, hydroxyethylcellulose, hydroxypropylmethylcellulose and poly-a~~rylic acid. Typical amounts for those: compounds are from 0.1 to 2 percent by weight.
A,n especially suitable complex; former is especially ethylenediaminetetraacetic acid, ahbreviated to EDTA, and salts thereof, such as sodium salts. Typical amounts for those c~~mpounds are from 0.01 to 1 percent by weight.
The contact lens care products according to the invention are suitable for all types of contact lenses. These include capeciall;y so-called hard and soft contact lenses, and also so-called hard-flexible or highly gas-permeable contact lenses. The contact lens care products according to the invention exhibit an antimicrobial action and, also, a cleaning acaion. Depending on the specific intended use, the contact lens care products according to the invention can be used as cleaning; solutions, disinfectants, or, for example, as solutions for storing, rinsing, abetting or soaking contact lenses. All those solutions are distinguished by good cleaning; and disinfecting action and a high degree of tolerability in a single solution.
In addition, while exhibiting better antvnicrobial activity, the contact lens care products according to the invention surprisingly exhibit significantly better cytotoxicity properties than do the care producta known from the prior art, for example Bausch &
Lomb's Kombi solution. The overall spectrum of properties of the contact lens care products according to the invention is therefore considered to be significantly superior to the properties of the contact lens care products known from the prior art.
The contact lens care products according to the invention are prepared in a manner known Q~r se, especially by conventional mixing of the constituents with water or dissolving of the constituents in water.
2(~984'~2 T'he compositions according to the invention are especially suitable for cleaning and disin-fecting contact lenses. The contact lens; care products according to the invention are used in a manner known her se, for example by bringing a contact lens into contact with the contact lens care product for a period o:f time sufficient for cleaning or disinfection.
>r~epending on the type of lens and the degree of contamination, a period of from several rr~inutes to about 24 hours, prei:erably up to approximately 4 to 12 hours, is sufficient.
A. preferred solution according to the invention comprises, for example, a~ninopropyl biguanide 0.0005 to 0.05 mg/ml 2-amino-2-hydroxymethyl-1,3~-propanediol 0.67 to 4.03 mg/ml 2-amino-2-hydroxymethyl-1,3--propanediol . HCl 2.64 to 4.02 mg/ml, the total amount of buffer being preferably less than 8 mg/ml and especially less than 6 mg/ml, and may preferably also comprise:
NaCI or KCl 3 to 9 mg/ml especially 5.5 to 9 mg/ml surface-active compound 5 to 30 mg/ml EDTA 0.1 to 2 mg/ml.
A solution according to the invention that is likewise preferred comprises, for example, aminopropyl biguanide 0.0005 to 0.05 mg/ml 2-amino-2-hydroxymethyl-1,3-propanediol 1.00 to 4.00 mg/ml especially about 2.5 mg/ml and small amounts of HCl to establish the desired pH range.
The desired pH range of the compositions according to the invention is especially approx-imately 7.0 to 7.5, preferably from 7.1 to 7.4 and especially preferably 7.3.
T:he following Examples serve to illustrate the invention. They are not, however, intended to limit the scope of the invention in any way, and especially not to the subject-matter of the Examples.
2~~~~"~2 _7-F;xample 1: Formulation for soft contact lenses 1 ml of solution comprises:
aminopropyl biguanide (Arlagard~) 0.005 mg 2-amino-2-hydroxymethyl-1,3-propanediol 0.97 mg 2-amino-2-hydroxymethyl-1,3-propanediol ~ HCl 6.61 mg 1'TaCI 6.6 mg poloxamer 407 10 mg >=;DTA 1 mg.
>=;xample 2: Formulation for herd contact lenses 1 ml of solution comprises:
aminopropyl biguanide (Arlag;ard~) 0.005 mg 2-amino-2-hydroxymethyl-1,3-propanediol 0.97 mg 2-amino-2-hydroxymethyl-1,3-propanediol 6.61 mg ~ HCl rfaCl 6.6 mg poloxamer 407 10 mg EDTA 1 mg polyvinyl alcohol 14 mg.
Example 3: Formulation for soft contact lenses 1 ml of solution comprises:
aminopropyl biguanide (Arlag~~rd E~) 0.005 mg 2-amino-2-hydroxymethyl-1,3--propanediol 1.39 mg 2-amino-2-hydroxymethyl-1,3-propanediol ~ HCl 6.06 mg I~ aCI 5.5 mg p~~loxamer 407 10 mg EDTA 1 mg.
Example 4: Antimicrobial acti'r~
The formulation of Example 3 is tested against the following test organisms:
Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Aspergillus niger. The following Table shows the initial inoculum as well as the number of organisms 20984'2 _g_ still to be found after the formulation of Example 3 has been allowed to act for a period of 4. hours and of 6 hours:
7.'est organism initial number of number of inc~culum organisms organisms after after 4 hours 6 hours Facherichia coli 6.8 - 105 0 0 Staphylococcus aureus8.9' ~ 105 0 0 F'seudomonas aeruginosa1.0' - 106 0 0 C:andida albicans 1.1 - 106 2.7 - 105 1.8 - 105 ~cspergillus niger 1.1 - 106 b.2 - 105 1.1 - 106 I:n contrast, the following values are determined for Bausch & Lomb's Renu solution comprising aminopropyl bigu~~nide (0..'i ppm) and a borate buffer:
Test organism initial number of number of inoculum organisms organisms after after 4 hours 6 hours F,scherichia coli 6.8 - 105 9.5 - 101 4.3 - 101 Staphylococcus aureus8.9 - 105 5.7 - 101 3.8 - 101 Pseudomonas aeruginosa1.0 ~ 106 0 0 C'andida albicans l . l - 106 4.9 - 105 6.2 - 105 A,spergillus niger 1.1 - 106 5.5 ~ 105 4.3 - 105 Example 5: Cytotoxicity test In order to determine the cytot~~xic potential, the formulation of Example 3 is subjected to the growth inhibition test and compared with Bausch & Lomb's Kombi solution.
In this teat the decrease in cell growth in the presence of toxic compounds is determined by c~~mparing the protein content of treated cell cultures with the protein content of untreated call cultures after 72 hours' incubation. The test solutions are serially diluted with the cell culture medium (DMEM-FCS j. L 929 cell cultures are incubated for 72 hours in the presence of solutions of various concentrations. It is found that the solution according to 20984'2 presence of solutions of various concentrations. It is found that the solution according to the invention induces cytotoxic effects only at concentrations of 20 % v/v, while the Kombi solution already induces cytotoxic effects at concentrations of 5 % v/v.
In the test carried out, the protein content is a measure of the cell growth or the inhibition of growth induced by toxic substances. Growth inhibition of more than 30 %
compared with untreated cultures is considered to be a clear cytotoxic effect.
Solution A): Formulation according to Example 3 Concentration of the solution (% v/v] 20.0 10.0 5.0 2.5 1.3 0.6 Growth inhibition [%] 32 11 4 4 2 0 Solution B): Kombi solution from Bausch & Lomb Concentration of the solution [% v/v] 20.0 10.0 5.0 2.5 1.3 0.6 Growth inhibition [%] 92 68 40 25 11 7 These results demonstrate that the Kombi solution already induces cytotoxic effects at a dilution lower by a factor of 4, namely at 5 % v/v, compared with the formulation accord-ing to Example 3 with which such effects occur only with 20 % v/v solutions.
Example 6: Formulation fo:r hard contact lenses 1 ml of solution comprises:
polyaminopropyl biguanide: (Cosmocil~)0.002 mg 2-amino-2-hydroxymethyl-1,3-propanediol2.5 mg NaCI 7.5 mg poloxamer 407 10 mg hydroxyethylcellulose 3.2 mg EDTA 1 mg HCl to adjust pH
20984'~~
Example 7: Formulation fo:r soft contact lenses 1 ml of solution comprises:
polyaminopropyl biguanide: (Cosmocil~) 0.001 mg 2-amino-2-hydroxymethyl-1,3-propanediol2.45 mg NaCI 7.4 mg poloxamer 407 1.0 mg EDTA ~ 0.25 mg HCl to adjust pH
Example 8: Antimicrobial activity The formulation according to Example 6 is tested against the following test organisms:
Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Aspergillus niger. The following Table indicates the initial inoculum and the number of organisms still to be found .after the formulation of Example 6 has been allowed to act for a period of 6 hours:
Test organism initial number of inoculum organisms after 6 hours Escherichia coli 1.1 106 0 -Staphylococcus aureus1.4 106 0 -Pseudomonas aeruginosa1.3 106 0 -Candida albicans 1.2 i06 4.1 ~ 105 -Aspergillus niger 5.7 i05 2.8 - 105 -Example 9: Cytotoxicit~te;~t Analogously to Example 5 'the formulation according to Example 6 is subjected to the growth inhibition test. The test shows that the solution according to the invention induces only extremely slight cytotoxic effects even at concentrations of 20 % v/v, while the Kombi solution already induces significant cytotoxic effects at concentrations of 5 % v/v (see Example 5).
209$4'2 Solution according to Exar~iple 6 Concentration of solution [% v/v] 20.0 10.0 5.0 2.5 1.3 0.6 growth inhibition [%] 12 S 0 0 0 3
Contact lens care products comprising an aminopropyl biguanide are already known. For 'example, GB 1432 345 describes ophthalmic compositions and compositions for disin-fecting contact lenses comprising an ophthalmologically acceptable polymeric biguanide.
Only phosphate buffers are disclosed as suitable buffers in that context.
EP-A1-180 309 also discloses.disinfecting and preserving solutions for contact lenses, comprising a biguanide and a buffer. The biguanide is again of the aminopropyl biguanide type. As buffer especially borate buffers are proposed. Additional buffers mentioned are citrate buffers, bicarbonate buffers and mixed phosphate buffers.
In contrast, the present invention relates to contact lens care products comprising an aminopropyl biguanide or a salt thereof and as buffer the so-called tris buffer (trometamol) or a homolog thereof having up to 10 carbon atoms or a salt thereof. The invention relates also to the use of such a contact lens care product for cleaning and disinfecting contact lenses.
-1a-According to one aspect of the present invention, there is provided a contact lens care product comprising an aminopropyl biguanide of formula NH NH
HzN-(CHz)3 (CHz)3-N-C-N-C-N-(CHz)3 (CHz)3-NHz H H H n (I) or a salt thereof and as buffer from 0.05 to less than 1.2 percent by weight of a compound of formula (CHz) y OH
to H~ (CHz)X-i-NHz (CHz) Z OH
(III) or a salt thereof, wherein n is an integer from 1 to 500, x, y and z are each independently of the others an integer, at least 1, and the sum of x, y and z is from 3 to 9.
The aminopropyl biguanides to be used according to the invention are especially those of formula I
NH NH
HzN- (CHz) 3 (CHz) 3 -H -C-H-C-H-(CHz) 3 n (CHz) 3' NHz (I) wherein n is an integer from 1 to 500; it is also possible to use salts of compounds of formula I, especially ophthalmologically acceptable salts thereof.
The compounds of formula I are known. Their preparation is described, for example, in C~B 702 268 and GB 1 152 24?.. In addition, those compounds are also commercially available, for example as Vant~xil~, Cosmocil~ or as Arlagard~E from ICI
Chemicals.
Depending on the manner in which they have been prepared, the compounds of formula I
rnay comprise certain amounts of a secondary product of formula II
NH NH
H2N-(CH2)3~H2)3-NH-C-rTH-~-NH-(CH2)~(CH2)3-NH-C-NH-CN (II) -J n o:r salts thereof, wherein n is likewise an integer from 1 to 500. Mixtures of compounds of formula I with those of formuhr II can likewise be used according to the invention. The proportion of compounds of formula II, based on the total amount of compounds of formula I and compounds of formula II., is preferably less than 20 percent by weight, more preferably less than from 2 to 10 percent by weight and is especially preferably zero percent by weight.
The index n in formulae I and lI is preff;rably from 1 to 200, especially from 2 to 100, more especially from 2 to 50 arid most especially from 3 to 12. Depending on the value of the index n in formula I or II, the molecular weight of the aminopropyl biguanides that can be: used is as low as the molecular weight of the monomer of formula I (n =
1), or in the raurge of approximately 600 to 1600 if oligomers are used, i.e. when n is, for example, from 3 to 8, or alternatively in the range of from approximately 50 000 to approximately 90 0100 if n is significantly higher, for e;cample approximately 270 to 500.
In the contact lens care products according to the invention, the compound of formula I is used preferably in an amount, based on the total amount of the contact lens care product, which is advantageously formulated as .an aqueous solution, of from 0.1 to 100 ppm (0.00001 - 0.01 percent by weight), especially in an amount of from 0.5 to 50 ppm (Ci.OC1005 - 0.005 percent by weight) and more especially in an amount of from 1 to ppm (0.0001 - 0.001 percenr. by weight), for example 1, 2 or 5 ppm.
S~rlts of compounds of formula I and formula II that are suitable within the scope of the present invention are water-soluble salts that are advantageously ophthalmologically acceptable. Suitable salts are those with inorganic or organic acids, for example hydro-chlorides, hydrobromides, borates, acetates, gluconates, sulfonates, maleates, ascorbates, 2Q~84'~2 _3_ tartrates or citrates.
T'he trometamol and its homologs having up to 10, preferably from 5 to 7, carbon atoms used according to the invention preferably are the compounds of formula III
( i H2 Iy-OH
HO-(CH2)X-C-NH2 (III) (CH2 )Z OH
v~~herein x, y and z are each independently of the others an integer, at least 1, and the sum of x, y and z is from 3 to 9, preferably from 3 to 6, or a salt thereof.
Special preference is given to 2-amino-2-hydroxymethyl-1,3-propanediol (trometamol), which corresponds to a compound of formula III wherein each of x and y and z is 1. The compound trometamol is a:~so referred to as tris buffer.
Trometamol and its homologs leaving up to 10 carbon atoms are already known.
Their use in medicaments for the treatment of inf7,ammations of the eye has already been disclosed in EP-A2-242 328. Compositions for the disinfection of contact lenses, comprising 1.2 tromethamine/tromethamine hydrochloride and 1 ppm polyhexamethylene biguanide hydrochloride, are already kno~,vn from WO 92/11876. Compounds of formula III
are, rr,,oreover, also commercially available.
The amount of trometamol used as buffer in the contact lens care products according to the invention, based on the total amount of the contact lens care product, is preferably from 0.05 to 5 percent by weiglht, preferably from 0.1 to 2.5 percent by weight and especially preferably from approximately 0.2 to approximately 1.5 percent by weight. The amount of trometamol used as huffer in the contact lens care products according to the invention, based on the total amount of the contact lens care product, is more especially from 0.05 to less than 1.2 percent by weight or from 0.05 to less than 0.8 percent by weight, very especially from 0.1 to 0.6 percent by weight, especially from 0.1 to less than 0.6 percent by weight, for example up to 0.5 percent by weight.
2-Amino-2-hydroxymethyl-1,3-propane.diol or a homolog thereof having up to 10 carbon atoms, or a salt thereof, can be used alone as buffer. Alternatively, one of the above-mentioned compounds can be used together with a salt thereof. Again, preference is given 20984'2 here to the use of ophthalmolo;gically acceptable salts, such as the salts mentioned above in connection with compounds of formula I. Especially suitable are the hydrochlorides or maleates of compounds of formula III, i.e., for example, a combination of 2-amino-2-hydroxymethyl-1,3-propanediol with the hydrochloride of 2-amino-2-hydroxymethyl-1,3-propanediol, or a combination of 2-amino-2-hydroxymethyl-1,3-propanediol with the maleate of 2-amino-2-hydroxymethyl-1,3-propanediol or 2-amino-2-hydroxymethyl-1,3-propanediol, to which smaa.l amounts of hydrochloric acid are added.
T'he contact lens care products according to the invention preferably do not comprise buffers other than compounds of formula III. They may, however, comprise other buffers in addition to one or more compounds of formula III.
The contact lens care products according to the invention are preferably formulated in such a manner that they are isotonic wish lachrymal fluid. They may in general comprise additives that are customary fo:r contact lens care products. Those include, for example, compounds that influence tonicity, surface-active compounds, compounds that influence viscosity, or complex formers. The contact lens care products according to the invention comprise those or other customary additives in amounts that vary within the range of the values familiar to the person skilled in the art.
A. solution that is isotonic with lachrymal fluid is generally understood to be a solution the concentration of which corresponds to the concentration of a 0.9 % sodium chloride solution. Departures therefrom are entirely possible, provided that the contact lenses to be treated are not damaged thereby. Isotonicity with lachrymal fluid or a different desired tonicity can be established by t:he addition of organic or inorganic compounds that influence tonicity. The former can be used, for example, in amounts of approximately 1 to 4.5 percent by weight, the latter in amounts of approximately 0.1 to 1.3 percent by weight.
In general, the amount of the compound that influences tonicity that is added is such that the tonicity of the composition according to the invention is especially in the range of from 200 to 450 milliosmols, preferably in the range of from approximately 270 to approximately 330 milliosmols. Typical organic compounds of that type are, for example, glycerol, urea, propylene glycol or sugars, such as mannitol or sorbitol, and typical inorganic compounds of that type are especially potassium chloride and sodium chloride.
Mixtures of those compounds with one another can also be used according to the invention.
Suitable surface-active compounds are mentioned, for example, in EP-A2-180 309.
Examples of especially suitable representatives that can be used according to the invention are poloxamer types and miranol types,. Other representatives are known to a person skilled in the art. Those compounds can be used, for example, in amounts of up to 20 percent by weight, espe:ciahly in amounts of from 0.4 to 5 percent by weight.
Suitable compounds that influence viscosity are also known to a person skilled in the art.
Examples of especially suitabhe representatives that can be used according to the invention are polyvinyl alcohol, hydroxyethylcellulose, hydroxypropylmethylcellulose and poly-a~~rylic acid. Typical amounts for those: compounds are from 0.1 to 2 percent by weight.
A,n especially suitable complex; former is especially ethylenediaminetetraacetic acid, ahbreviated to EDTA, and salts thereof, such as sodium salts. Typical amounts for those c~~mpounds are from 0.01 to 1 percent by weight.
The contact lens care products according to the invention are suitable for all types of contact lenses. These include capeciall;y so-called hard and soft contact lenses, and also so-called hard-flexible or highly gas-permeable contact lenses. The contact lens care products according to the invention exhibit an antimicrobial action and, also, a cleaning acaion. Depending on the specific intended use, the contact lens care products according to the invention can be used as cleaning; solutions, disinfectants, or, for example, as solutions for storing, rinsing, abetting or soaking contact lenses. All those solutions are distinguished by good cleaning; and disinfecting action and a high degree of tolerability in a single solution.
In addition, while exhibiting better antvnicrobial activity, the contact lens care products according to the invention surprisingly exhibit significantly better cytotoxicity properties than do the care producta known from the prior art, for example Bausch &
Lomb's Kombi solution. The overall spectrum of properties of the contact lens care products according to the invention is therefore considered to be significantly superior to the properties of the contact lens care products known from the prior art.
The contact lens care products according to the invention are prepared in a manner known Q~r se, especially by conventional mixing of the constituents with water or dissolving of the constituents in water.
2(~984'~2 T'he compositions according to the invention are especially suitable for cleaning and disin-fecting contact lenses. The contact lens; care products according to the invention are used in a manner known her se, for example by bringing a contact lens into contact with the contact lens care product for a period o:f time sufficient for cleaning or disinfection.
>r~epending on the type of lens and the degree of contamination, a period of from several rr~inutes to about 24 hours, prei:erably up to approximately 4 to 12 hours, is sufficient.
A. preferred solution according to the invention comprises, for example, a~ninopropyl biguanide 0.0005 to 0.05 mg/ml 2-amino-2-hydroxymethyl-1,3~-propanediol 0.67 to 4.03 mg/ml 2-amino-2-hydroxymethyl-1,3--propanediol . HCl 2.64 to 4.02 mg/ml, the total amount of buffer being preferably less than 8 mg/ml and especially less than 6 mg/ml, and may preferably also comprise:
NaCI or KCl 3 to 9 mg/ml especially 5.5 to 9 mg/ml surface-active compound 5 to 30 mg/ml EDTA 0.1 to 2 mg/ml.
A solution according to the invention that is likewise preferred comprises, for example, aminopropyl biguanide 0.0005 to 0.05 mg/ml 2-amino-2-hydroxymethyl-1,3-propanediol 1.00 to 4.00 mg/ml especially about 2.5 mg/ml and small amounts of HCl to establish the desired pH range.
The desired pH range of the compositions according to the invention is especially approx-imately 7.0 to 7.5, preferably from 7.1 to 7.4 and especially preferably 7.3.
T:he following Examples serve to illustrate the invention. They are not, however, intended to limit the scope of the invention in any way, and especially not to the subject-matter of the Examples.
2~~~~"~2 _7-F;xample 1: Formulation for soft contact lenses 1 ml of solution comprises:
aminopropyl biguanide (Arlagard~) 0.005 mg 2-amino-2-hydroxymethyl-1,3-propanediol 0.97 mg 2-amino-2-hydroxymethyl-1,3-propanediol ~ HCl 6.61 mg 1'TaCI 6.6 mg poloxamer 407 10 mg >=;DTA 1 mg.
>=;xample 2: Formulation for herd contact lenses 1 ml of solution comprises:
aminopropyl biguanide (Arlag;ard~) 0.005 mg 2-amino-2-hydroxymethyl-1,3-propanediol 0.97 mg 2-amino-2-hydroxymethyl-1,3-propanediol 6.61 mg ~ HCl rfaCl 6.6 mg poloxamer 407 10 mg EDTA 1 mg polyvinyl alcohol 14 mg.
Example 3: Formulation for soft contact lenses 1 ml of solution comprises:
aminopropyl biguanide (Arlag~~rd E~) 0.005 mg 2-amino-2-hydroxymethyl-1,3--propanediol 1.39 mg 2-amino-2-hydroxymethyl-1,3-propanediol ~ HCl 6.06 mg I~ aCI 5.5 mg p~~loxamer 407 10 mg EDTA 1 mg.
Example 4: Antimicrobial acti'r~
The formulation of Example 3 is tested against the following test organisms:
Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Aspergillus niger. The following Table shows the initial inoculum as well as the number of organisms 20984'2 _g_ still to be found after the formulation of Example 3 has been allowed to act for a period of 4. hours and of 6 hours:
7.'est organism initial number of number of inc~culum organisms organisms after after 4 hours 6 hours Facherichia coli 6.8 - 105 0 0 Staphylococcus aureus8.9' ~ 105 0 0 F'seudomonas aeruginosa1.0' - 106 0 0 C:andida albicans 1.1 - 106 2.7 - 105 1.8 - 105 ~cspergillus niger 1.1 - 106 b.2 - 105 1.1 - 106 I:n contrast, the following values are determined for Bausch & Lomb's Renu solution comprising aminopropyl bigu~~nide (0..'i ppm) and a borate buffer:
Test organism initial number of number of inoculum organisms organisms after after 4 hours 6 hours F,scherichia coli 6.8 - 105 9.5 - 101 4.3 - 101 Staphylococcus aureus8.9 - 105 5.7 - 101 3.8 - 101 Pseudomonas aeruginosa1.0 ~ 106 0 0 C'andida albicans l . l - 106 4.9 - 105 6.2 - 105 A,spergillus niger 1.1 - 106 5.5 ~ 105 4.3 - 105 Example 5: Cytotoxicity test In order to determine the cytot~~xic potential, the formulation of Example 3 is subjected to the growth inhibition test and compared with Bausch & Lomb's Kombi solution.
In this teat the decrease in cell growth in the presence of toxic compounds is determined by c~~mparing the protein content of treated cell cultures with the protein content of untreated call cultures after 72 hours' incubation. The test solutions are serially diluted with the cell culture medium (DMEM-FCS j. L 929 cell cultures are incubated for 72 hours in the presence of solutions of various concentrations. It is found that the solution according to 20984'2 presence of solutions of various concentrations. It is found that the solution according to the invention induces cytotoxic effects only at concentrations of 20 % v/v, while the Kombi solution already induces cytotoxic effects at concentrations of 5 % v/v.
In the test carried out, the protein content is a measure of the cell growth or the inhibition of growth induced by toxic substances. Growth inhibition of more than 30 %
compared with untreated cultures is considered to be a clear cytotoxic effect.
Solution A): Formulation according to Example 3 Concentration of the solution (% v/v] 20.0 10.0 5.0 2.5 1.3 0.6 Growth inhibition [%] 32 11 4 4 2 0 Solution B): Kombi solution from Bausch & Lomb Concentration of the solution [% v/v] 20.0 10.0 5.0 2.5 1.3 0.6 Growth inhibition [%] 92 68 40 25 11 7 These results demonstrate that the Kombi solution already induces cytotoxic effects at a dilution lower by a factor of 4, namely at 5 % v/v, compared with the formulation accord-ing to Example 3 with which such effects occur only with 20 % v/v solutions.
Example 6: Formulation fo:r hard contact lenses 1 ml of solution comprises:
polyaminopropyl biguanide: (Cosmocil~)0.002 mg 2-amino-2-hydroxymethyl-1,3-propanediol2.5 mg NaCI 7.5 mg poloxamer 407 10 mg hydroxyethylcellulose 3.2 mg EDTA 1 mg HCl to adjust pH
20984'~~
Example 7: Formulation fo:r soft contact lenses 1 ml of solution comprises:
polyaminopropyl biguanide: (Cosmocil~) 0.001 mg 2-amino-2-hydroxymethyl-1,3-propanediol2.45 mg NaCI 7.4 mg poloxamer 407 1.0 mg EDTA ~ 0.25 mg HCl to adjust pH
Example 8: Antimicrobial activity The formulation according to Example 6 is tested against the following test organisms:
Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Aspergillus niger. The following Table indicates the initial inoculum and the number of organisms still to be found .after the formulation of Example 6 has been allowed to act for a period of 6 hours:
Test organism initial number of inoculum organisms after 6 hours Escherichia coli 1.1 106 0 -Staphylococcus aureus1.4 106 0 -Pseudomonas aeruginosa1.3 106 0 -Candida albicans 1.2 i06 4.1 ~ 105 -Aspergillus niger 5.7 i05 2.8 - 105 -Example 9: Cytotoxicit~te;~t Analogously to Example 5 'the formulation according to Example 6 is subjected to the growth inhibition test. The test shows that the solution according to the invention induces only extremely slight cytotoxic effects even at concentrations of 20 % v/v, while the Kombi solution already induces significant cytotoxic effects at concentrations of 5 % v/v (see Example 5).
209$4'2 Solution according to Exar~iple 6 Concentration of solution [% v/v] 20.0 10.0 5.0 2.5 1.3 0.6 growth inhibition [%] 12 S 0 0 0 3
Claims (11)
1. A contact lens care product comprising an aminopropyl biguanide of formula or a salt thereof and as buffer from 0.05 to less than 1.2 percent by weight of a compound of formula or a salt thereof, wherein n is an integer from 1 to 500, x, y and z are each independently of the others an integer, at least 1, and the sum of x, y and z is from 3 to 9.
2. A contact lens care product according to claim 1 wherein the aminopropyl biguanide is a mixture of a compound of formula I, or a salt thereof, wherein n is an integer from 1 to 500, with a compound of formula II, or a salt thereof, wherein n is likewise an integer from 1 to 500.
3. A contact lens care product according to claim 1 wherein the aminopropyl biguanide is a compound of formula I
wherein n is an integer from 1 to 500, or a salt of a compound of formula I, and wherein the buffer is trometamol or a salt thereof.
wherein n is an integer from 1 to 500, or a salt of a compound of formula I, and wherein the buffer is trometamol or a salt thereof.
4. A contact lens care product according to claim 1 comprising as a buffer from 0.05 to less than 0.8 percent by weight of a compound of formula (III) or a salt thereof.
5. A contact lens care product according to claim 1 comprising as a buffer from 0.1 to 0.6 percent by weight of a compound of formula (III) or a salt thereof.
6. A contact lens care product according to claim 1 comprising aminopropyl biguanide 0.0005 to 0.05 mg/ml 2-amino-2-hydroxymethyl-1,3-propanediol 1.00 to 4.00 mg/ml especially about 2.5 mg/ml and HC1 to establish a pH of from 7.0 to 7.5.
7. A contact lens care product according to any one of claims 1 to 6 comprising in addition one or more additives selected from compounds that influence tonicity, surface-active compounds, compounds that influence viscosity and complex formers.
8. A contact lens care product according to claim 1 comprising polyaminopropyl biguanide (Cosmocil®) 0.002 mg/ml 2-amino-2-hydroxymethyl-1,3-propanediol 2.5 mg/ml NaCl 7.5 mg/ml poloxamer 407 10 mg/ml hydroxyethylcellulose 3.2 mg/ml EDTA 1 mg/ml and HCl to adjust the pH.
9. A contact lens care product according to claim 1 comprising aminopropyl biguanide (Cosmocil® 0.001 mg/ml 2-amino-2-hydroxymethyl-1,3-propanediol 2 mg/ml NaCl 7.4 mg/ml poloxamer 407 1.0 mg/ml EDTA 0.25 mg/ml and HC1 to adjust the pH.
10. The use of a contact lens care product according to any one of claims 1 to 9 for one or both of cleaning and disinfecting a contact lens.
11. A method of cleaning or disinfecting a contact lens which comprises bringing a contact lens care product according to any one of claims 1 to 9 into contact with a contact lens for a period of time sufficient for one or both of cleaning and disinfection.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP92810467 | 1992-06-17 | ||
| EP92810467.8 | 1992-06-17 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2098472A1 CA2098472A1 (en) | 1993-12-18 |
| CA2098472C true CA2098472C (en) | 2004-01-06 |
Family
ID=8211941
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2098472 Expired - Lifetime CA2098472C (en) | 1992-06-17 | 1993-06-15 | Contact lens care product for hard and soft contact lenses |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JP3423357B2 (en) |
| AT (1) | ATE337023T1 (en) |
| CA (1) | CA2098472C (en) |
| DE (1) | DE59310389D1 (en) |
| FI (1) | FI932683A (en) |
| IL (1) | IL105972A (en) |
| MX (1) | MX9303587A (en) |
| NO (1) | NO307450B1 (en) |
| NZ (1) | NZ247890A (en) |
| SG (1) | SG47420A1 (en) |
| TW (1) | TW203128B (en) |
| ZA (1) | ZA934268B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1259542A (en) * | 1984-09-28 | 1989-09-19 | Francis X. Smith | Disinfecting and preserving solutions for contact lenses and methods of use |
| JP3698832B2 (en) * | 1996-10-08 | 2005-09-21 | 株式会社メニコン | Contact lens solution |
| DE69735963T2 (en) | 1996-12-13 | 2007-01-25 | Alcon Laboratories, Inc., Fort Worth | Amino-containing ophthalmic compositions |
| ZA9811445B (en) | 1997-12-19 | 1999-08-16 | Alcon Lab Inc | Aminobiguanides and the use thereof to disinfect contact lenses and preserve pharmaceutical compositions. |
| JP2002532462A (en) | 1998-12-18 | 2002-10-02 | アルコン ラボラトリーズ，インコーポレイテッド | Bis-amide polybiguanides and their use for sterilizing contact lenses and for preserving pharmaceutical compositions |
| EP1140805A1 (en) | 1998-12-18 | 2001-10-10 | Alcon Laboratories, Inc. | Amido polybiguanides and the use thereof as antimicrobial agents |
| JP4902064B2 (en) * | 2000-08-16 | 2012-03-21 | 株式会社クラレ | Contact lens solution |
| JP5092138B2 (en) * | 2001-08-30 | 2012-12-05 | ライオン株式会社 | Contact lens mounting fluid |
| JP4634024B2 (en) * | 2003-10-23 | 2011-02-16 | 株式会社シード | Contact lens solution |
| WO2012005311A1 (en) * | 2010-07-06 | 2012-01-12 | ロート製薬株式会社 | Composition for contact lens care |
| JP2012145967A (en) * | 2012-05-07 | 2012-08-02 | Lion Corp | Contact lens wetting solution |
| JP5673721B2 (en) * | 2013-04-04 | 2015-02-18 | ライオン株式会社 | Contact lens mounting fluid |
-
1992
- 1992-07-25 TW TW81105907A patent/TW203128B/en not_active IP Right Cessation
-
1993
- 1993-06-08 AT AT93810410T patent/ATE337023T1/en not_active IP Right Cessation
- 1993-06-08 DE DE59310389T patent/DE59310389D1/en not_active Expired - Lifetime
- 1993-06-08 SG SG1996000995A patent/SG47420A1/en unknown
- 1993-06-10 IL IL10597293A patent/IL105972A/en not_active IP Right Cessation
- 1993-06-11 FI FI932683A patent/FI932683A/en unknown
- 1993-06-15 CA CA 2098472 patent/CA2098472C/en not_active Expired - Lifetime
- 1993-06-15 NZ NZ24789093A patent/NZ247890A/en unknown
- 1993-06-16 MX MX9303587A patent/MX9303587A/en unknown
- 1993-06-16 ZA ZA934268A patent/ZA934268B/en unknown
- 1993-06-16 JP JP14450893A patent/JP3423357B2/en not_active Expired - Lifetime
- 1993-06-16 NO NO932224A patent/NO307450B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO932224L (en) | 1993-12-20 |
| AU660090B2 (en) | 1995-06-08 |
| CA2098472A1 (en) | 1993-12-18 |
| SG47420A1 (en) | 1998-04-17 |
| NO307450B1 (en) | 2000-04-10 |
| FI932683A (en) | 1993-12-18 |
| ZA934268B (en) | 1993-12-17 |
| ATE337023T1 (en) | 2006-09-15 |
| DE59310389D1 (en) | 2006-10-05 |
| NO932224D0 (en) | 1993-06-16 |
| TW203128B (en) | 1993-04-01 |
| IL105972A (en) | 1999-09-22 |
| JPH0667123A (en) | 1994-03-11 |
| MX9303587A (en) | 1994-01-31 |
| JP3423357B2 (en) | 2003-07-07 |
| IL105972A0 (en) | 1993-10-20 |
| FI932683A0 (en) | 1993-06-11 |
| AU4125293A (en) | 1993-12-23 |
| NZ247890A (en) | 1994-12-22 |
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