TW203128B - The protection method for hard and soft contact lens - Google Patents

Abstract

This invention relates to contact lens dressing in which comprising aminopropylbiguanid and salts thereof, especially of compound of formula I(see claim 1), in which n is an integer of 1 to 500 or salts of formula I, and the Tris-Buffer (trigydroxymethylaminomethane) or its homologous comprised at least C10(the 10rd power) and salts thereof. This invention also relates to the application of cleaning and disinfection by the contact lens dressing.

Description

L03128 Λ 6 it ο V. Description of the invention () The present invention relates to a protective agent for hard and soft contact lenses containing (poly) liminoguanidine (Aminopropylbiguanide) and a special buffer. Protective agents for contact lenses containing alanine are known. For example, the ophthalmic composition described in British Patent Nos. 1, 4 2 3, and 3 4 5 and the disinfection composition of the oval glasses include an ophthalmologically approved biguanide polymer. However, suitable buffers in these compositions are all phosphate buffers. European Patent A1-180, No. 309, published in the disinfection and protection solution of big glasses, contains biguanide and buffer solution. The biguanide is also of the amine-propane type. The buffer solution is particularly a borate buffer solution. In addition, it can also be a citrate salt, hydrogen sulfonate and mixed phosphate buffer solution. However, the contact lens protector of the present invention contains alaproguanidine or its salt and the buffer is trimethylolamine (TRIS or Trometaaiol®) or its homologues or salts containing up to C10. The invention also relates to the application of such contact lens protectant in cleaning and disinfecting contact lenses. The amidoguanidine used in the present invention is especially shown in formula I:

NH H2N- (CH2) 3 (I) (please read the precautions before writing this page) The Ministry of Economic Affairs Central Standards Bureau Beigong Consumer Cooperative Printed Department Eyes are the special formula I ο ο 5 to 1 0 is the salt η, which can be represented by Xu Yinghua and so on-containing this E record, < E > la system number ΑΓ its 43 or, 2 '® 0 2 1 know 5 i J 1 C already, 〇ij 1 t is η and a is f is V 6 I in 2 name 2 products 70 purchased by the company Publicly available Xueli Chemical Specialized Items [01 Guohe t This paper standard uses the Chinese National Standard (CNS) A 4 specifications (210X297 mm > 81. 7. 20,000 ^ (11) ^ 03128 Λ 6 ι > ο V. Description of the invention (During the production of compound II by the employee consumption cooperation of the Central Bureau of Standards of the Ministry of Economic Affairs, there will be fixed by-products II or their salts, ΝΗ ΝΗ νηH2N- (CH2) 3 ^ CH2) 3-NH-C- NH- (I: -NH- (CH2) j- (CH2) 3-NH-(!:-NH-CN (11) where η is also 1 to 500. Compounds I and II can be used according to the invention A mixture of compound II is preferably 20% or less of the total weight of compounds I and II, particularly preferably 2 to 10% or less, and most preferably 0%. The index η in formulas I and II is preferably 1 to 200, particularly preferably 2 to 100, particularly preferably 2 to 50, and most preferably 3 to 12. The value of η in formula I or II depends on the molecular weight of the applicable aminetidine, for example, if η is as low as 1, Formula I is that the molecular weight of the monomer is the molecular weight of the monomer; if η is 3 to 8, the molecular weight is the molecular weight of the oligomer About 600 to 1600; if the η value is higher, such as about 270 to 5Q0, the molecular weight range is about 5,0G0 to about 90,000. In the contact lens protective agent of the present invention, the compound I is preferably accounted for 0.1 to 100ppm by weight (0.G0001 to 0.01%), particularly preferably 0.5 to 50ppb (0. 0 0 0 0 5 to 0.0 0 5%), preferably 1 to 10 ?? | 〇 ((). 〇001 to 0. () 01%), for example, 5 ?? 111 (0.0005%) 0 Suitable salts of compounds I and Η of the present invention refer to ophthalmologically approved water-soluble salts, which are the reaction of the compound with inorganic or organic acids Formed by, such as hydrochloride, hydrobromide, borate, acetate, gluconate, sulfonic acid (please read the back-end precautions # fill out this page) β Β home «quasi (CNS) Τ 4 specifications (210 father 297 mm) 8 !. 7. 20,0005 ^ (1!)

5. Description of the invention () Salt, tartrate or citrate. The trimethylolmethane used in the present invention and the homologues containing up to c10, preferably cs-, are shown in formula III:

(CH2) y-〇H HO- (CH2) x-C-NH2 (ΠΙ)

'(CH2) 2-〇H In the formula, X, y and Z are independent of each other, and are integers of at least 1, and the sum of x + y + z is 3 to 9, preferably 3 to 6, and salts thereof can also be used. Preferably, X, y, and z are all 1, that is, the formula III is 2-amine-2-hydroxymethyl-1,3-propanediol. This compound is commonly known as TRIS buffer. TRIS and homologues up to C10 are known, and European Patent A2-242,328 states that it can be used in anti-inflammatory drugs for eyes. Compound m is also commercially available. In the contact lens protector of the present invention, the T RIS buffer accounts for 0.05 to preferably 0.1 to 2.5% of the total weight of the contact lens protection, and most preferably about 0.2 to about 1.5%. The buffering agent can be printed by 2-amine-2-hydroxymethyl-1,3-propanedi, the Ministry of Economic Affairs Central Standards Bureau Employee Consumer Cooperative (please read the precautions first and write this page) alcohol (卽 三 hydroxy Methylamine methane) or homologues containing C10 or salts thereof. Mixtures of the aforementioned compounds and their salts can also be used. The salts are of course ophthalmologically approved salts. Also suitable is the hydrochloride salt of compound III, for example, a mixture of 2-amine-2-hydroxymethyl-1,3-propanediol and its hydrochloride salt. Although the contact lens protector of the present invention may contain one or more compounds, it is preferable not to contain the compound m as a buffer. The protective agent for contact lenses of the present invention is preferably formulated to be mixed with tears and other pressures. The paper size is not the same as that of the Chinese sleeper «quasi (CNS) T4 specification (210X297)> 81. 7. 20,000 ^ (11) ^ 03128

Printed by the Beigong Consumer Cooperative of the Ministry of Economic Affairs, Standards Bureau, M Λ 6 ι> ο_ V. Description of the invention (). It may generally contain additives commonly used in contact lens protectors, such as osmotic pressure regulators, surfactants, viscosity agents or complexing agents. The amount of these and other commonly used additives in the protector for horn glasses of the present invention is familiar to experts. The concentration of the solution containing tear water and other osmotic pressure regulator is the same as the concentration of the salt water containing 0.95! As long as the treated contact lens is not damaged, its concentration can vary within a certain range. Tear osmotic pressure or other desired osmotic pressure can be adjusted with organic or inorganic osmotic pressure regulators. The former can be used in an amount of about 1 to 3.5% by weight, while the latter can be used in an amount of about 0.1 to 1.3% by weight. Typical organic substances of this type are, for example, glycerin, urea, propylene glycol or sugars, such as mannose; typical inorganic substances of this type are especially vaporized calcium or sodium chloride. Mixtures of these compounds can be used according to the invention. Suitable surfactants are described in European Patent A2-180, 309. Particularly suitable representative examples that can be used in the present invention are hydroxyalkylene type (P ο 1 ο X a hier ®) or Milan alcohol type (Miranol ®) surfactants, and other surfactants known to experts. The amount of these substances can be up to 20% by weight, especially 0.4 to 5% by weight. Suitable viscosity modifiers are also known to experts. Other suitable materials which can be used in the present invention are, for example, polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropylmethylcellulose or polyacrylic acid. Typical amounts are 0.1 to 2% by weight. Particularly suitable complexing agents are in particular ethylenediaminetetraacetic acid (slightly EDTA) and its salts, such as the sodium salt. The typical dosage of these substances is 0.01 to 1% by weight (please read the precautions before filling in this page) Binding · Threading--6-This paper standard is not used in Zhongming "Home Sample Standard (CNS) A 4 Specifications (210X297 mm) 81. 7. 20,000 ^ (II) 203128 Printed by the Employee Consumer Cooperative of the Bureau of Standards of the Ministry of Economic Affairs V. Description of the invention Comparing with the previous solution, the better protective agent for contact lens lens is according to the present invention. 0 · 0 0 0 5 to 0 · 6 7 to 4. The hard and soft lenses of the shape glasses. This cleaning function can be done. The storage and cleaning capacity is high, so the protective agent, in comparison, the full protective agent of the fungus active and more protective agent is suitable for all types of contact lenses, package lenses, and so-called semi-hard or highly invented contact lens protective agents There must be sterilization. For special purposes, the present invention is a cleaning agent, disinfectant, or wetting or softening solution for contact lenses. All such solutions can have both cleaning and disinfecting functions. For example, Bausch & Lomb The contact lens protector invented by Kombi exhibits surprisingly good cytotoxicity. Therefore, the "..." of the present invention is significantly better than the previous contact lenses. The dissolved 0.05 mg / 03 mg / ml solution contains, for example: ml of alanine, 64 to 7. G2 mg / ml is particularly preferred and still contains 3 to 9 mg / ml 5 to 30 mg / ml 0.1 to 2 mg / ml is not to limit the present invention (please read the precautions before filling this page) Binding · Binding-2-amine-2 -hydroxymethyl-1, 3-propanol 2-amine-2 -Hydroxymethyl-1,3-propanediamine • Hydrochloride vaporized sodium or potassium vaporized surfactant EDT A Scope Example Description The present invention The paper scale is used in the country a National Standard (CNS) f 4 Specifications (210x297 g *) 81. 7. 20,000 ^ (II) 0312b Λ 6 V. Description of the invention (: Soft-type Chen Xing Sui Xi Xi g square 1 ml solution 0.005 mg 0.97 mg 6.6 1 Mg 6.6 mg 10 mg 1 mg Example 2: Hard formula; Contains: Alanine (Arlagard®) 2-amine-2-hydroxymethyl-1, 3-propanediol 2-amine-2-hydroxymethyl-1 , 3-Propanediol. Hydrogenate sodium gasification Surfactant (Poloxamer® 407) EDT A 铷 形 _ 钟 用 方 (Please read the back-to-back precautions #Cube write this page) 1 ml of solution 0 0 0 5 mg 0.97 mg 6. 6 1 mg 6 . 6 mg 10 mg 1 mg 14 mg Example 3: Soft form contains alanine (Arlagard®) 2-amine-2-hydroxymethyl-1, 3-propanediol 2-amine-2-hydroxymethyl-1 , 3-Propanediol. Hydrochloride Sodium Chloride Surfactant (Poloxamer® 407) EDTA Polyvinyl Alcohol_Formal Bell Use: > BR Square Pack-Order_ Line · Central Ministry of Economic Affairs Employee Consumer Cooperative Print 1 ml of solution containing 0.005 mg of amine-propanediguanide (Arlagard®E) 1.39 mg of 2-amine-2-hydroxymethyl-1, 3-propanediol 6.10 mg 5.5 mg of amine-2-hydroxyl Methyl-1,3-propanediol • Hydrohydrate sodium gasification This paper standard is not used in China National Standard (CNS) A 4 (210x297 g *) 81. 7. 20t000iic (I!)% 03128 Λ 6 Ministry of Economic Affairs Printed by the Central Bureau of Standards EX Gongxiao Cooperative V. Description of the invention () 10 mg of surfactant (P 〇1 〇 丨 X a .me Γ⑧ 4 0 7) 1 mg of E DT A Example Left * Kill m If the formulation of Example 3 was used to test the fighting effect of the following bacteria: Escherichia coli aureus, M. aureus, M. aeruginosa *, Streptococcus spp. 9 black bacterium 〇 The following table lists the number of original inoculations>, and the treatment of the formulation of Example 3 4 And the number of bacteria after 6 hours; test the bacterial count 4 hours after the original inoculation of the bacterial species 6 hours after the number of bacteria The number of bacteria intestinal m 6. 8X1 0 E 0 0 Aureus aureus 8. 9X1 0-0 0 marginal membrane Bacillus 1.0) < 1 0 e 0 0 Streptococcus 1.1 X 1 0 e 2. 7 X 1 0 5 1. 8 X 1 0 Aspergillus niger 1.1 X 1 0 e 6. 2 X 1 0 5 1. IX 10 Example fS: Emperor detoxification test p. Growth inhibition test Comparative Example 3 The cytotoxicity of the formulation and the Kombi® solution produced by Bausch & L 0 B b. In this test, the protein content in the treated cell culture medium and the protein content in the untreated cell culture medium after 7 2 hours of incubation are compared to know the inhibition of cell growth in the presence of toxic substances. The test solution is a series of Cell culture medium dilution (D HE M-FC S) 0 Incubate the cell culture medium in various high-concentration solutions for 7 2 hours. The results show that the concentration of the solution of the present invention at 20% volume will cause the cell poisoning effect »Ko mb > The solution is at 5% -9-(please read the back-to-back precautions # fill in this page) The paper size is easy to use Zhongming country «quasi (CNS) T 4 specifications (210 father 297 male dragon) 81.7 . 20,000 ^ (11) Printed by the Ministry of Economic Affairs, Central Bureau of Punctuation, and β Cooperative Society pm .____ V. Description of the invention () The volume concentration is the phenomenon of cell poisoning. In this test, the protein content obtained by cell growth will be inhibited by toxic substances to reduce the protein content. Comparing the untreated culture, the growth inhibition rate is greater than 3G%, which obviously has the effect of cytotoxicity. Solution A: The concentration of the formulation solution according to Example 3 is 2 GG 1 0. 0 5.0 2. 5 1. 3 0. F (% volume) Growth inhibition rate 3 2 1 1 4 4 2 0 (%) Solution B: Bausch & The concentration of Koaibi® solution produced by Lomb Company is 2 0.0 1 0. 0 5. 0 2.5 1. 3 0 .t (% volume) Growth inhibition rate 92 6 8 40 25 11 7 (° / 〇) From the above data, Kombi® When the solution is diluted 4 times (that is, the concentration is 5: ϋ volume), it has the effect of cell poisoning, and compared with Example 3, the phenomenon starts at 20% volume concentration. (Please read the precautions first and then write this page) Installation · Thread _ -10- This paper size is easy to use in the B sleeper «quasi (CNS) T4 specifications (210x297; 81. 7. 20,00 ) ¾ (II)

Claims (1)

£ 03128 Λ7 B7 C7 D7 VI. Patent application No. 8 1 1 0 5 9 ti No. 7 Patent Case for "Protection Agent for Hard and Soft Oval Glasses" (Amended in February 2002) _ Agent, which contains amidoguanidine or its salt, and 2-amine-2-hydroxymethyl-1,3-propanediol as a buffer or its content. The same article or its salts. 2. The hard and soft contact lens protector according to item 1 of the patent application scope, in which the imiproguanidine compound formula I: NH H2N- (CH2) 3 ^ 2) 3-NH-C-NH- (I: -NH -(CH2) j- < CH2) 3- (I) where n is an integer from 1 to 500, or a salt of formula 1. 3. The hard and soft contact lens protector according to item 1 of the patent application scope, in which amidoguanidine is a compound of formula I or a salt thereof NH NH H2N- (CH2) 3HCH2) 3-NH-C-NH-c !: -NH-(CH2) 3j < CH2) 3-NH2 (I) --------------------------- install -------- 、 玎 --- ,, ---. ^ (Please read the precautions on the back before writing this page) The Ministry of Economic Affairs, China Bureau of Standards, β Industry and Consumer Cooperation, Du Yin K, where η is an integer from 1 to 500, The compound of formula Π or a mixture of its salts. This paper scale is applicable to China National Standard (CNS) A 4 specifications (210 X 297 mm) 03128 A7 B7 C7 D7 VI. Patent application scope NH H2N- (CH2) 3- (CH2) 3-NH-C-NH-C !: -NH- (CH2) ^ (CH2) 3-NH- (!: -NH-CN (π) where η is also an integer from 1 to 5 0 0 The hard and soft contact lens protector according to item No. of the scope of the patent application, in which the buffer is a compound of formula ffi or its salts: (CH2) y-〇HI HO- (CH2) xC-NH2 (CH2) z- OH (ΠΙ) where X, y and ζ are independent, the pseudo-integer is at least 1, and the sum of x + y + z is 3 to 9.. According to the patent application scope of the hard and soft contact lens protector, in which Amalidine Compound formula I: ------------------------ installed ------ ordered ------ line (please read the back side first Matters needing attention will be written on this page) Printed by the Ministry of Economic Affairs, Central Bureau of Standards, Wr & C Cooperative «NH II NH -C-NH- H2N- (CH2) 3 (tCH2) 3_NH-C_NH.iNH. (CH2 ^ CH2) rNH2 (I ) This paper scale is applicable to China National Standard (CNS) Grade 4 (210 X 297 mm) 03128 2.64 to 7.02 mg / ml Printed by the Central Standardization Bureau of the Ministry of Economic Affairs κε Gongxiao F Cooperative Society Λ7 B7 C7 .D7 k, application In the patent scope formula, n is an integer from 1 to 500, or a salt of formula I, and the buffer is pseudotrimethylolmethane or its salts. 6. The hard and soft contact lens protector according to the first item of the patent scope of the application, which contains 0.05 to 0.05 mg / ml aminoprimidine 0.67 to 4.03 mg / ml 2-amine -2-hydroxymethyl-1, 3-propanediol 2-amine-2-hydroxymethyl-1, 3-propanediol · hydrogen acid 7. According to the patent application scope item 1, the hard and soft type of protective glasses glasses, which It also contains additives selected from Osmotic® modifiers, surfactants, viscosity modifiers and complexing agents. 8. The hard and soft contact lens protector according to item 1 of the patent scope of the application, which contains 0.0005 to 0.05 mg / ml aminetinidine 0.67 to 4.03 mg / ml 2-amine- 2-Hydroxymethyl-1, 3-Propion ------------ Packing ----- 1T --- 1-- -Marry (please read the notes on the back before writing this page) 2.64 to 7.02 mg / ml 3 to 9 mg / ml 5 to 30 € g / ml 0.1 to 2 mg / ml diol 2-amine-2 -Hydroxymethyl-1,3-Propanediol • Hydroxyhydrogenate sodium oxychloride or chloride surfactant EDTA (Ethylenediaminetetraphenolic acid) -3-This paper applies to China National Standards (CNS) A4 specifications ( 210 X 297 mm) v 〇3i ^ ® B7 C7 D7 VI. Scope of patent application The lens-protected eye-shaped soft type I and the hard 0 items should be the 1st mirror-shaped eye-shaped model. According to Jie Genqing, the seed agent is 0 ---------------------- IT ------ Line * (Please read the precautions on the back before writing this page) The Central Standards Bureau of the Ministry of Economic Affairs and Industry Consumer Cooperation Du Yin «This paper is again applicable to the Chinese National Standard (CNS) A 4 specifications (210 X 297 X #)