A kind of composition and application thereof for the treatment of contact lenses
Technical field
The present invention relates to a kind of for cleaning, sterilization, storing contact lenses and as composition and the application thereof of intraocular wetting solution.
Technical background
Usually, contact lenses are divided into hard contact lenses and soft contact lens two large classes substantially. The hard contact lenses water content is below 10%, quite durable, simultaneously, the character of lens materials is not also carried electric charge, thereby, when wearing with this kind eyeglass, thereby and need not worry especially in the eyeglass absorption tear that materials such as protein-based, lipid or microorganism causes discomfort and the injury to eyeball, so the oculist generally agrees with to this kind of wearer's recommendation eyeglass. But because the hard contact lenses deformation behavior is relatively poor, it is strong to be worn in the eye foreign body sensation, and it is relatively poor just to wear adaptability, and the consumer is more prone to select to possess good deformation behavior, wears comfortable soft contact lens.
Current soft contact lens all is gel, hydrogel or the soft lens that the monomer polymerization of employing such as methacrylic acid-2-hydroxyethyl ester makes, its water affinity is very high, and most with electric charge, these characteristics determine that it is in use or preservation process, be easy to grow microorganism, be easy to depositing proteins and lipid, be easy to adsorb the Cucumber macromolecular substances of polarity (for example have), and all these materials all may damage wearer's eyeball. Solution is that eyeglass is effectively nursed, existing a lot of reports, as: (1) is killed the microorganism that grows---and no matter be in the use procedure or in storing (the polylysine method as described in the JP17418196); (2) eyeglass deposit (particularly protein) is removed---available proteolysis enzyme process or chemical method (such as the method as described in the United States Patent (USP) 3910296). In all cases, for fear of infection, soft contact lens all needs termly to carry out cleaning and disinfection (in some cases even all will carry out in every morning or evening) with conditioning liquid. But this has problem on the other hand: because height water affinity, it is (improper if the wearer nurses rules that eyeglass can residual absorbed portion conditioning liquid composition, residual composition can be more), along with eyeglass is worn again into intraocular, these compositions are also and then brought intraocular into, and a lot of components such as the bactericide reported in the prior art, active protease component, ion chelating agent etc., all may have spread effect to eyes. This brings another kind of uncomfortable even injury to the wearer again.
On the other hand, the wearing into the normal physiological state that has changed eyes of contact lenses, " barrier " of contact lenses effect stops that cornea causes the anoxic of ocular tissue with contacting of air. Simultaneously, need tear moistening except original angle, conjunctival surface, more than the inside and outside surface of eyeglass, cause the tear amount to lack, so that the wearer feels that eye dryness is with uncomfortable. In addition, because the attaching of contact lenses and eye mask is rotated, renewal and the exchange of tear have been hindered again, cause gathering of products of cellular metabolism, particularly be positioned at the tear layer of eyeglass rear surface, if can not flow for a long time renewal, will corneal produce very adverse influence. In order to address the above problem, people use the Eye Care liquid with certain eye health-care effect usually, such Eye Care liquid does not have the nursing role to eyeglass, in other words, people must prepare two kinds of liquid: be respectively applied to lens care and Eye Care when using contact lenses. This has increased again the inconvenience in people's use.
Thereby, be sought after a kind ofly can effectively cleaning contact lenses, can make again eyeglass after processing, can wear safely into eyes, and also can be used for nursing the multipurpose contact lens care solution of eyes in the nursing eyeglass while, with the needs of satisfying the market.
Summary of the invention
The present invention provides a kind of composition for the treatment of contact lenses and application thereof. Said composition is the aqueous solution that includes Sodium Hyaluronate, tonicity agents, surfactant, chelating agent, buffer and bactericide, can be used for cleaning, sterilization, stores contact lenses or as the intraocular wetting solution. Said composition is to eye effect safety, can keep eye moistening and improve the comfort level of contact lens wear person's eye.
The composition of the present composition and content are: the hyaluronic acid sodium content is 0.0001-1wt%, preferred 0.001-0.5wt%; Nonionic surface active agent content is 0.0001-30wt%, preferred 0.001-10wt%; Tonicity agents is to make composition osmotic pressure be adjusted to 220-350mOsm/
KgH
2O, preferred 280-310mOsm/KgH2The amount of O; Chelating agent content is 0.001-30wt%, preferred 0.01-10wt%; Buffer content is 0.005-5wt%, preferred 0.05-2.5wt%; Bactericide content is amount and the water surplus of its effective bacteriocidal concentration.
Hyaluronic acid (Hyaluronic acid) has another name called Hyaluronic Acid, is by extracting in the animal tissue or through the macromolecule mucopolysaccharide that bacterial fermentation obtains, being the macromolecular chain shape polysaccharide that is made of D-Glucose aldehydic acid and 2-Acetamido-2-deoxy-D-glucose amine. Different according to its degree of polymerization, molecular weight can be from several ten thousand to millions of dalton, wait the carboxyl on the glucuronic acid residue of space length to make it have unique character. As the essential material of a kind of physiology, hyaluronic acid is distributed widely in the tissue, is the Main Ingredients and Appearance that consists of connective tissue. Be distributed between histocyte in the matter main Physiological Functions such as performance cell adhesion, osmotic pressure adjusting as large molecule glycosaminoglycan. The animal eyeball vitreum contains a large amount of hyaluronic acids, and corneal stroma is to be produced by the hyaluronic acid network structure to the resistance of water fully, and this structure is to keeping cornea form stable tool important function. Hyaluronic acid also is clearly to protection and the affects on the growth of cell, and certain density hyaluronic acid can promote the cell increment. Hyaluronic acid is brought into play its important function by physics characteristics such as its viscoplasticity (macromolecular network structure) and high degree of hydration in body or outside the body, hyaluronic acid can promote obviously that anterior corneal surface water liquid retains and to improve cornea moist, the present invention is through experiment confirm, and hyaluronic acid makes the present composition can play well the effect of wetting contact lenses. The surfactant with good cleansing power that comprises in this composition and the bactericide with good bactericidal properties, and they may have potential excitant to eye mucosa, but the present composition experimental results show that seldom or almost do not show spread effect, wherein be exactly that the component hyaluronic acid has slowed down the possible spread effect of these components, also play simultaneously the repair to the damage keratocyte. Therefore, hyaluronic acid is to the wet performance of the eyeglass processed through the present composition and to increase eyeglass be to play a significantly greater role in the greasy property of anterior corneal surface.
Usually, when (pH neutral), its carboxyl dissociates hyaluronic acid in vivo, exists with the form of its salt, and the present invention mainly uses its sodium salt (be Sodium Hyaluronate, this paper to it referred to as HA).
Generally, the Sodium Hyaluronate that molecular weight is less than normal, more obvious to the protection nourishing effect of cell, molecular weight Sodium Hyaluronate bigger than normal then has significantly lubricated moistening effect. The Sodium Hyaluronate molecular weight that the present invention selects is 1 * 105-3×10
6, consumption is 0.0001-1wt%, take 0.001-0.5wt% as preferred.
Selecting as asking the maximum comfortable of eye and irriate not of bactericide, the toxicity such as chlohexidine and mercurous compounds are higher, generally will not select the stronger material of eye irritation; And quaternary ammonium salt such as benzalkonium chloride (Benzalkonium Chloride) are easily absorbed by soft lens, and be also inapplicable. The present invention selects safe bactericide to comprise one or more mixture in sorbic acid, polyaminopropyl biguanide (PAPB), EDTA, the iodine class etc. Its consumption is the amount of effective bacteriocidal concentration.
Tonicity agents is to make composition solution more comfortable to the user. The present composition is adjusted near the nature tear with tonicity agents, namely is equivalent to the osmotic pressure of 0.9wt% sodium chloride solution. Hypotonic and height oozes and will cause the eye pain and stimulate, and the tonicity agents commonly used such as normal operation NaCl, KCl also can select glucose, xylitol, glycerine etc. to be tonicity agents. Consumption is that adjusting composition osmotic pressure is 220-350mOsm/KgH2O is preferably 270-330mOsm/KgH2O, more preferably 280-310mOsm/KgH2The amount of O.
The present composition maintains pH6-8 for well with buffer, preferred pH7.0-7.4. Buffer can select borate, phosphate, carbonate, acetate, Tris (trihydroxy methyl ammonia methane), HEPES[4-(α-hydroxyethyl)-1-piperazine ethane sulfonic acid], any one or more mixture that can effectively play cushioning effect such as citrate, as long as its solution can be by biocompatible and the comfort level that do not affect eye all can select. Borate and phosphate are buffers preferably. Wherein more preferably borate buffer when playing cushioning effect, also can effectively play the effect of assisting sterilisation, and toxicity is lower. Generally, the consumption of buffer is about 0.005-5wt%, preferred 0.05-2.5wt%.
The present invention also comprises the surfactant that the deposit on the contact lenses is had cleaning active, to guarantee that this composition possesses good clenaing effect, they are by being combined with clastic facies with lipid, the protein of lens surface, make itself and eyeglass in conjunction with becoming loose, wash easily. Have in this area that many surfactants are all known to can be used as main cleaning agent, comprise anion surfactant, cationic surfactant, non-ionic surface active agent and amphoteric surfactant. The present invention is when the option table surface-active agent, pay attention to its cleaning performance, more pay attention to its biocompatibility and to the excitant of eyes, select chemistry and good biocompatibility, and can effectively play the nonionic surface active agent that reduces the surface tension of liquid effect, select one or more the mixture such as poloxamer (poloxamer is polyoxyethylene and polyoxypropylene block polymer), polyethylene glycol (PEG), polysorbate, polysiloxanes, polyoxyethylene alkyl ether, glyceride, glucose ester, ethoxylated phenol yuban, APG. Preferred poloxamer and PEG. The Poloxamer compound claims again poloxamine, and the title that to be ClFA Cosmetic Ingredient Dictionary adopt this class surfactant has about 7500-27000 molecular weight. This compounds can be from BASF Wyandotte corp., Wyandotte, and Michigan obtains with registration mark " Tetronic ". The common consumption of surfactant is 0.0001-30wt%, preferred 0.001-10wt%.
The present composition also comprises a certain amount of chelating agent with bind metal ion, and the proteins react of avoiding on metal ion and the eyeglass deposition and gathering also plays certain assisting sterilisation effect simultaneously. Chelating agent of the present invention is selected one or more the mixture in EDTA and sodium salt, glycine, citric acid, boric acid, gluconic acid, butanedioic acid, tartaric acid or the phosphate, preferred EDTA and sodium salt thereof. Usually its consumption is 0.001-30wt%, preferred 0.01-10wt%.
The present composition can be used for cleaning, sterilizes, stores contact lenses, also can be used as the intraocular wetting solution and is used for moistening eye and lubricated eyeglass.
Cleaning eyeglass can be exposed to eyeglass in this composition, preferably all be immersed in the composition, then can or stir eyeglass by friction (available clean finger pulp loss or other suitable vessel), then use this composition rinsing (or rushing Xian) eyeglass, the dirt of wash-out is washed away. Another scheme of cleaning eyeglass is that eyeglass is immersed in the sufficiently long time in this composition, and then rinsing can be finished lens cleaning a little. Because this composition seldom or does not almost have excitant, the eyeglass after the cleaning can directly be worn into intraocular.
This composition also can be used for sterilization and stores eyeglass, preferably eyeglass is immersed in certain hour in this composition fully, finishes the sterilization to eyeglass, and in this case, this composition also can be used for the storage of eyeglass.
The present composition also can be used as the intraocular wetting solution and directly splashes into the intraocular that wears contact lenses, is used for moistening eye and lubricated eyeglass. Perhaps, can in eye, take out contact lenses, wear into intraocular again after using this composition moistening a little. The present composition also can be used for being unworthy of wearing the intraocular of contact lenses as general intraocular wetting solution. Advantage of the present invention:
The present composition has rationally effectively prescription, and have suitable osmotic pressure and an acid-base value, make the HA that contains in the prescription can effectively alleviate the unfavorable factor that other component may have to eye mucosa potential stimulus, make the present composition seldom or almost do not show spread effect. The present composition has good effect to the removing of eyeglass residual protein, and clean rate can reach 39-56%. And colibacillus, green pus liver bacterium, the effective sterilizing rate of staphylococcus aureus all reached more than 99.99%, the sterilizing rate of Candida albicans is also reached more than 90%. And the present composition because component HA can increase cell proliferation, just can promote effectively that also composition is compatible with eyes simultaneously in effectively cleaning eyeglass proteinosis and effective killing microorganisms, and HA can effectively increase lubricity and the moisture retention of composition. Thereby this composition also can be used for alleviating owing to wear with the discomfort due to the contact lenses in the conditioning liquid while as lens cleaning, sterilization, storage simultaneously. Can reach the present composition and can effectively clean eyeglass deposition, the eyeglass after the cleaning is worn into intraocular safely, and have simultaneously increase eye comfortable, keep eye moistening, improve the function of tear exchange.
Preferred forms
Following specific embodiment will further specify preparation, use and the effect of the present composition. Be to be understood that these embodiment do not mean that limitation of the scope of the invention for illustrative purposes only. The final weight of composition solution is 1000 grams among the embodiment, and the weight of material is all with the gram expression.
Embodiment 1-2
Embodiment 1 and embodiment 2 (seeing Table 1) illustrate two preparation examples of present composition solution:
Table 1
Embodiment 1 | Embodiment 2 |
Component | Consumption (gram) | Component | Consumption (gram) |
NaCl
|
3.9
|
NaCl
|
3.85
|
HA (MW40 ten thousand) |
0.1
| HA (MW250 ten thousand) |
5.0
|
Sorbic acid |
6.7
| Sorbic acid |
6.7
|
HEPES
|
2.2
|
HEPES
|
2.2
|
Na
2HPO
4·2H
2O
|
0.9
|
Na
2HPO
4·2H
2O
|
0.9
|
NaH
2PO
4·H
2O
|
0.06
|
NaH
2PO
4·H
2O
|
0.06
|
Poloxamer |
10
| Poloxamer |
10
|
Polyaminopropyl biguanide |
2.0ppm
| Polyaminopropyl biguanide |
2.0ppm
|
Citric acid |
3.2
| Citric acid |
3.2
|
PEG400
|
20
|
PEG400
|
20
|
H
2O
| Add to 1000 |
H
2O
| Add to 1000 |
Preparation process: HA, Na2HPO·2H
2O、
NaH
2PO
4·H
2O, citric acid, 40 ℃ after the heating stirring and dissolving, are cooled to room temperature in a part of water, add all the other components, stir, and supply moisture to required weight, use NaOH solution or HCl solution to regulate pH to 7.2 ± 0.2, namely get composition solution. | | Preparation process: the NaOH solution of 20ml 10% is put water-bath heat to 70 ℃, drop into HA, stirring and dissolving is namely taken out, and adding citric acid solution while stirring again approaches neutrally to solution, and can get the HA stoste of thickness this moment. Get Na2HPO
4·2H
2O、NaH
2PO·H
2O, citric acid after 50 ℃ of heating stirring and dissolving, are cooled to room temperature, add HA stoste and other components, stir, and supply moisture to required weight, use NaOH solution or HCl solution to regulate pH to 7.2 ± 0.2, namely get composition solution. | |
Osmotic pressure |
308
| Osmotic pressure |
302
|
Acid-base value (pH value) |
7.17
| Acid-base value (pH value) |
7.25
|
Embodiment 3-6
With the described prescription of table 2 and be prepared into the composition with different amounts and molecular weight hyaluronic acid sodium by embodiment 1 method, test it to the impact of cell enlargement and comfort. Because cell experiment can accurately reflect the genotoxic potential of specimen objectively, conditioning liquid for contact lenses, normal this method that adopts is as the evaluation experimental of biocompatibility in the industry, as (reaction is classified as 0~4 grade to adopt the ISO9363-1 method of testing, progression is lower, and the biocompatibility of test material is better) or adopt the cell proliferation test of GB16886, weigh the biocompatibility of experiment material with relative relative growth rate (rgb value), the propagation degree is higher, and compatibility is better. The present invention adopts these two kinds of method of testings that embodiment 3-6 and reference examples 1 are tested and estimate simultaneously. After finishing cell experiment, proceed eye drip experiment and product beta test further product usefulness is estimated.
Table 2
| Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Reference examples 1 |
NaCl
|
4.4
|
4.4
|
4.4
|
4.4
|
4.4
|
Boric acid |
3.7
|
3.7
|
3.7
|
3.7
|
3.7
|
Boratex |
0.2
|
0.2
|
0.2
|
0.2
|
0.2
|
Na
2HPO
4·2H
2O
|
3.5
|
3.5
|
3.5
|
3.5
|
3.5
|
KH
2PO
4 |
0.5
|
0.5
|
0.5
|
0.5
|
0.5
|
KCl
|
0.2
|
0.2
|
0.2
|
0.2
|
0.2
|
PEG400
|
5
|
5
|
5
|
5
|
5
|
Poloxamer |
2.0
|
2.0
|
2.0
|
2.0
|
2.0
|
EDTA-2Na
|
1
|
1
|
1
|
1
|
1
|
HA
(MW=2.0×10
5)
|
0.01
| | |
5.0
| |
HA
(MW=1.8×10
6)
| |
0.1
| | | |
HA
(MW=1.8×10
6)
| | |
2.0
| | |
Sorbic acid |
2.0
|
2.0
|
2.0
|
2.0
|
2.0
|
H
2O
| Add to 1000 | Add to 1000 | Add to 1000 | Add to 1000 | Add to 1000 |
RGB(%)
|
130
|
119
|
117
|
121
| 100 (benchmark) |
Among four embodiment of above-described embodiment 3-6, different molecular weight (MW=2 * 10 have been selected respectively5And 1.8 * 106) Sodium Hyaluronate, change simultaneously its consumption to test it to the impact of cell enlargement and comfort, reference examples does not contain Sodium Hyaluronate. Five prescriptions all can reach the requirement (reaction rank: 0 grade) of ISO9361-1, when the method for employing GB GB16886 is tested, at second, four, seven day observation of cell propagation degree (RGB) of experiment, as benchmark, can obtain RGB result as shown in table 2 with reference examples 1. Above-mentioned cell experiment shows:
Real examination example all is better than reference examples, and cellular morphology is full among the embodiment, and the gap is fine and close, and cell number on average is higher than reference examples 10-20%. In each example, embodiment 3 is better than embodiment 4, and embodiment 4,5,6 is without large difference. This explanation, Sodium Hyaluronate is significantly to the effect of the compatibility of raising composition and organism, comparatively speaking, under the finite concentration, if the Sodium Hyaluronate molecular weight is on the low side, it is more obvious to improve the compatibility effect; If the Sodium Hyaluronate of HMW under finite concentration, also can more effectively promote the compatibility of composition and organism.
Carry out the eye drip test with the prepared composition solution of above embodiment 3-6 prescription, experimental subjects is divided into two groups, the group one be 20 without any eye illness, normal adults without contact lens wear history, the group second be 20 without eye illness, the healthy adult volunteer that above contact lens wear experience was arranged once, the comfort level to each example that the record experimental subjects is described is described (such as stimulation, uncomfortable, noninductive or comfortable); After eye drip experiment was finished, group one was proceeded experiment on probation, used embodiment and reference examples according to its routine use custom contrast, and embodiment and reference examples are used respectively a week, finish on probation after, lubricity and the performance of keeping humidity of sample are described, experimental result sees Table 3.
The result shows: with regard to total sensation, each embodiment is all without showing excitement or discomfort, level of comfort then is: experimental example 4=experimental example 6>embodiment 5=embodiment 3>reference examples, and the embodiment effect all is better than reference examples, especially feels the most comfortable with embodiment 4,6; With regard to lubricated, wettability, embodiment 5=embodiment 6>embodiment 4>embodiment 3>reference examples feels the most obvious with embodiment 5,6 especially. This result shows, in this composition, use HMW HA, with respect to LMW HA, even low consumption, more obvious lubricated sensation also can be arranged, but overall comfort level determines with the consumption height not only then, and depend on simultaneously molecular weight and consumption two factors, but generally speaking, adding HA is obvious with not adding the HA difference.
Table 3
Material | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Reference examples 1 |
Grouping | One | Two | One | Two | One | Two | One | Two | One | Two |
The eye drip experiment | Stimulate or discomfort |
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Noninductive |
8
|
3
|
2
|
1
|
5
|
6
|
1
|
3
|
15
|
16
|
Comfortable |
12
|
17
|
18
|
19
|
15
|
14
|
19
|
17
|
5
|
4
|
Experiment on probation: lubricated performance of keeping humidity evaluation | Obviously | |
7
| |
11
| |
15
| |
16
| |
0
|
Noninductive |
13
|
9
|
5
|
4
|
20
|
Embodiment 7-10
Prescription with following table 4 reaches the composition solution that is prepared into embodiment 7-10 by embodiment 1 method, deproteinized rate and the germicidal efficiency of test composition solution.
The composition that above-described embodiment adopts different buffers to form is tested its deproteinized cleaning efficiency and germicidal efficiency (the germicidal efficiency experimental technique adopts the method for GB15981-1995). Reference examples 2 (physiological saline) is without any sterilizing ability, each embodiment to Escherichia coli, Pseudomonas aeruginosa, the effective sterilizing rate of staphylococcus aureus all more than 99.99%, and to the sterilizing rate of Candida albicans also more than 90%.
Investigation can compare by following method the sedimental cleaning capacity of eyeglass: use composition solution to be tested to process the pretreated soft lens of albumin lysozyme soln, contrast liquid is at the ultraviolet light absorption value difference different (this is the protein difference that takes off) of processing the eyeglass front and back, take reference examples as benchmark, obtain relative deproteinized rate result as shown in table 4.
Experimental result shows: compare with simple physiological saline, each embodiment has good effect to the removing of eyeglass residual protein. Therein, embodiment 8,10 is better than embodiment 7,9,
The most obvious with embodiment 8 again, this shows that with respect to phosphoric acid buffer agent, the auxiliary deproteinized of borate buffer is more obvious.
Table 4
| Embodiment 7 | Embodiment 8 | Embodiment 9 | Embodiment 10 | Reference examples 2 |
NaCl
|
8.1
|
5.0
|
8.7
|
3.8
|
9.0
|
Na
2HPO
4·2H
2O
|
1.392
| |
0.900
|
5.642
| |
NaH
2PO
4·H
2O
|
0.354
| |
0.060
|
2.3
| |
Na
4B
2O
7·14H
2O
| |
0.9
| | | |
H
3BO
3 | |
6.4
| |
3.2
| |
EDTA-2Na
|
1.0
|
1.0
|
1.0
|
1.0
| |
Poloxamer |
2.0
|
2.0
|
2.0
|
2.0
| |
HA
(MW=1.2×10
6)
|
0.8
|
0.8
|
0.8
|
0.8
| |
Polyaminopropyl biguanide |
0.0010
|
0.0010
|
0.0010
|
0.0010
| |
H
2O
| Add to 1000 | Add to 1000 | Add to 1000 | Add to 1000 | Add to 1000 |
Deproteinized rate (%) |
44
|
56
|
39
|
47
| 0 (benchmark) |