CN110819464B

CN110819464B - Hard corneal contact lens care solution and preparation method thereof

Info

Publication number: CN110819464B
Application number: CN201910961780.9A
Authority: CN
Inventors: 龙雨
Original assignee: Shaanxi Renkang Pharmaceutical Co ltd
Current assignee: Shaanxi Renkang Pharmaceutical Co ltd
Priority date: 2019-10-11
Filing date: 2019-10-11
Publication date: 2020-12-08
Anticipated expiration: 2039-10-11
Also published as: CN110819464A

Abstract

The invention discloses a hard corneal contact lens care solution and a preparation method thereof, the hard corneal contact lens care solution comprises sitaxel, polyaminopropyl biguanide, edetate disodium, poloxamer, polyoxyethylene hydrogenated castor oil, hydroxyethylidene diphosphonic acid, hydroxypropyl betacyclodextrin, hydroxypropyl methylcellulose, propylene glycol, glycerol, mannitol, boric acid, sodium chloride and tris (hydroxymethyl) aminomethane, and can successfully treat proteins and bacteria adhered to a lens to achieve the effects of cleaning the lens and residual proteins; the anti-inflammation oil-in-water emulsion has the advantages that the connection of ICAM-1 is blocked, inflammation caused by corneal cell proliferation is prevented, and meanwhile, the anti-inflammation oil-in-water emulsion has good lubricity and reduces discomfort of a wearer in the initial wearing stage; has good oxygen transmission rate.

Description

Hard corneal contact lens care solution and preparation method thereof

Technical Field

The invention belongs to the technical field of care solution, and particularly relates to hard corneal contact lens care solution and a preparation method thereof.

Background

Rigid Gas Permeable Contact lenses (RGPs), which are called "breathing Contact lenses", are composed mainly of silicon-based fluorides, wherein polymers such as silicon and fluorine can greatly increase the oxygen throughput, reduce the ophthalmic inflammation and discomfort of the wearer, and are rapidly popularized in the global scope. The main problems of the nursing liquid matched with the nursing liquid are as follows:

1. because the RGP is worn differently from soft lenses, the RGP does not need to be taken off and cleaned every day, and thus the accumulation and proliferation of corneal cells of the eye are very easy to generate in the wearing process. Cell proliferation not only causes a decrease in RGP oxygen throughput, but also causes corneal inflammation, resulting in discomfort to the wearer. Therefore, the RGP care solution is different from the common soft lens care solution, and not only needs to clean substances such as residual protein on the lens, but also needs to ensure the adaptability of the lens and the cornea and reduce cell proliferation.

2. Different from the traditional soaking type care solution, the RGP care solution ensures that the lens is clean and sterilized and cannot influence the oxygen permeability of the lens.

The RGP mainly contains silicon-based fluoride, and can cause lens deformation after being soaked in a traditional care solution for a long time, mainly because part of bactericidal compounds and lens silicides are subjected to chemical reaction, so that the lens silicides are damaged, and the service life of the lens is influenced.

Disclosure of Invention

The hard corneal contact lens care solution and the preparation method thereof provided by the invention have good antibacterial effect, have the functions of cleaning, protein removal and metal ion removal, effectively improve the attachment rate of effective components, and have good oxygen transmission rate.

The specific technical scheme is as follows:

a hard corneal contact lens care solution comprises the following raw materials in parts by weight: 1-3 parts of sitaxel, 0.5-1.5 parts of polyaminopropyl biguanide, disodium edetate EDTA-2Na1-3 parts, 10-30 parts of poloxamer, 3-9 parts of polyoxyethylene hydrogenated castor oil, 2-6 parts of hydroxyethylidene diphosphonic acid, 5-15 parts of hydroxypropyl betacyclodextrin, 7-21 parts of hydroxypropyl methylcellulose, 10-30 parts of propylene glycol, 10-30 parts of glycerol, 20-60 parts of mannitol, 16-48 parts of boric acid, 3.4-10.2 parts of sodium chloride and 13-39 parts of tris (hydroxymethyl) aminomethane.

Preferably, the preparation method of the hard corneal contact lens care solution comprises the following steps:

weighing ammonia water, tetraethoxysilane, fluorocarbon surfactant and ethanol in corresponding parts, dividing the ethanol into two uniform parts, respectively mixing the two parts with the tetraethoxysilane and the ammonia water, stirring the mixture by magnetic force for 10min, gradually dripping the alcohol solution of the ammonia water into the alcohol solution of the tetraethoxysilane, and stirring the mixture for 5min while dripping; heating to 60 deg.C, using ultrasonic oscillator with power of 1200W and frequency of 60KHz, slowly dripping propylene glycol and glycerol in the oscillation process, ultrasonically oscillating for 20min, and stirring for 2 h. Adding 0.1 wt% of fluorine surfactant into the reaction system, and then fully stirring and uniformly mixing to obtain silicon dioxide nano sol; filling low-pressure pure inert gas into a high-vacuum chamber, placing sodium chloride particles into a high-temperature evaporator, heating to 1500 ℃ by a heating device to gasify sodium chloride, bringing sodium chloride steam into a cooling rod filled with liquid nitrogen by inert gas convection, and collecting the generated sodium chloride nanoparticles; and mixing the raw materials with the silica nano sol to prepare the care solution.

Preferably, the preparation material ratio of the silica nano sol is as follows: 1-2 parts of ammonia water, 15-25 parts of ethyl orthosilicate, 0.01-0.1 part of fluorosurfactant, 78-88 parts of ethanol, 3-10 parts of propylene glycol and 3-10 parts of glycerol.

Preferably, the preparation method of the care solution comprises the following specific steps:

soaking hydroxypropyl methylcellulose and hydroxypropyl betacyclodextrin in water for 4-6 hr; adding water into the polyaminopropyl biguanide, edetate disodium, poloxamer, polyoxyethylene hydrogenated castor oil, hydroxyethylidene diphosphonic acid, propylene glycol, glycerol, treated sodium chloride, boric acid, tris (hydroxymethyl) aminomethane and lithostat, heating to 50 ℃, and dissolving for later use; and then mixing mannitol and the silicon dioxide nano sol according to the volume ratio of 1:200, putting the mixture into a stirrer, heating to 50 ℃, stirring for 10min, and cooling to room temperature to obtain the care solution.

Preferably, the obtained care solution is treated by an ultrafiltration device with the aperture of 100A degrees.

Preferably, the silica nanosol is used as a carrier liquid of a hard corneal contact lens care solution.

Has the advantages that:

1. the invention adopts the mutual matching of the sitagliptin (Lifitegrast) and other raw materials, and effectively blocks the combination of the two through simulating the structure of intercellular adhesion molecules and lymphocyte function-related antigen necklace parts, thereby inhibiting the adhesion between leukocytes and endothelial cells, blocking the connection of ICAM-1 and preventing the inflammation caused by the proliferation of corneal cells.

2. The invention adopts the combination of the sitaxel, the polyoxyethylene hydrogenated castor oil, the hydroxyethylidene diphosphonic acid and the polyaminopropyl biguanide, and the terminal guanidine group of the polyaminopropyl biguanide can interact with groups and elements in organisms to generate destructive effect, so the polyaminopropyl biguanide is frequently applied to disinfection and sterilization. Through soaking treatment, the protein and bacteria adhered to the lens can be successfully treated by the poly-aminopropyl biguanide and the hydroxyethylidene diphosphonic acid, so that the effects of cleaning the lens and residual protein are achieved; the sitagliptin acts on a contact part of a lens and the cornea of an eye in a mode of attaching the lens to block the connection of ICAM-1, prevents inflammation caused by the proliferation of corneal cells, and the polyoxyethylene hydrogenated castor oil increases the lubrication between the cornea and the lens, reduces the uncomfortable feeling of a wearer in the initial wearing period, reduces the friction between the lens and the cornea and prevents the cornea from being hyperemic and inflamed.

3. Since part of the active ingredient of the present invention needs to be attached to the lens to exert its effect, such as sitaxel and polyoxyethylene hydrogenated castor oil, etc., it is difficult to achieve a good attaching effect with a common aqueous solution. The lens soaked in the common aqueous solution has the effective component adhesion rate of only 18.5 percent of sitaxel and 10.2 percent of polyoxyethylene hydrogenated castor oil. If the traditional organic solvent is adopted, the adhesion rate of active ingredients can be effectively improved, however, the oxygen permeability of the lens can be seriously influenced, and part of the organic solvent can cause fluoride and silicide of the lens to be damaged, so that the lens is deformed, and the service life of the lens is influenced. According to the invention, the mannitol and the silicon dioxide nano sol are mixed according to the volume ratio of 1:200 and then placed into a stirrer, heated to 50 ℃, stirred for 10min and cooled to room temperature, so that the active ingredients in the invention can be effectively supported, and the adhesive property is strong, and no irritation is caused to eyes. Because RGP is the lens that is used for the eye, and the active ingredient of nursing liquid is mostly nonpolar organic matter again, so the metal ion nanometer sol of commonly using not only can not effectively bear the active ingredient in the nursing liquid, still can produce the stimulation to the eye, produces the side effect. The method can fully exert the high bearing capacity of the nano sol without generating side effects, and the adhesion rate of the effective components is 68.5 percent of sitaxel and 82.2 percent of polyoxyethylene hydrogenated castor oil which are obviously improved compared with aqueous solution, and the oxygen permeability is increased, so that the oxygen permeability of the lens is not hindered.

4. The silica nano sol has stronger bearing capacity, but sodium chloride exists in the effective component of the invention, and sodium chloride particles are larger and can not be carried by the nonpolar silica nano sol, so the invention adopts the steps of placing the sodium chloride particles in a high-temperature evaporator, heating the sodium chloride particles to 1500 ℃ by a heating device, gasifying the sodium chloride, and smashing the sodium chloride particles into nano particles by an inert gas convection mode. The nano sodium chloride can be completely supported by the silica nano sol, cannot generate granular sensation in the care solution, and can meet the osmotic pressure regulation effect. The method adopts a mode of placing sodium chloride particles in a high-temperature evaporator, heating the sodium chloride particles to 1500 ℃ through a heating device to gasify the sodium chloride, bringing sodium chloride vapor into a cooling rod filled with liquid nitrogen through inert gas convection, and collecting generated sodium chloride nanoparticles, so that the sodium chloride is better dissociated into ions, and the osmotic pressure of the sodium chloride is better exerted; the suspension was freeze-dried rapidly with liquid nitrogen to remove water and ammonia, and a porous composite was obtained, which was a product with good stability.

5. In the transportation process, the nursing liquid is easy to deteriorate at high temperature, the nursing liquid is not easy to deteriorate at low temperature, but the nursing liquid is easy to condense at low temperature, is not suitable for storage and transportation and affects the use of the nursing liquid, the method of heating to 60 ℃, adopting an ultrasonic oscillator, the power of 1200W and the frequency of 60KHz, slowly dripping propylene glycol and glycerol in the oscillation process, stirring for 2 hours after ultrasonic oscillation for 20 minutes, adding 0.1 weight percent of fluorine surfactant in a reaction system, and then fully stirring and mixing uniformly to obtain silicon dioxide nano sol ensures the stability of a diffusion double electric layer, ensures the electrostatic interaction among particles to be kept in a stable state, simultaneously can ensure zeta potential, Brownian motion and enough solvent barrier to play good coalescence stability and kinetic stability in the whole system, and avoids the condensation phenomenon caused by weakening of one party, meanwhile, one third of propylene glycol and glycerol in parts by weight are added into the silica sol, other substances are not added, the sol molecules can be filled, the molecular distance is increased, and the silica molecules are blocked to prevent aggregation and agglomeration; in addition, the sol is treated by an ultrasonic oscillation method, so that the forming of the sol can be effectively accelerated, the movement of silicon dioxide molecules can be accelerated, and the molecular gap is enlarged, so that the finally obtained care solution has good low-temperature resistance, is not easy to coagulate, and is suitable for storage and transportation.

Drawings

FIG. 1: bar graph of cytostatic rate;

FIG. 2: a schematic diagram of drug adhesion results;

FIG. 3: schematic diagram of the application part of the gauze piece for skin irritation test, wherein 1-head part, 2-application care solution, 3-application normal saline, 4-tail part, 5-application normal saline and 6-application care solution are adopted.

Detailed Description

The present invention will be described in detail with reference to examples.

Example 1:

the preparation material ratio of the silica nanosol of the present embodiment is as follows: 1.5 parts of ammonia water; 20 parts of ethyl orthosilicate; 0.5 part of fluorine surfactant; 78 parts of ethanol; 3 parts of propylene glycol and 6 parts of glycerol; dividing ethanol into two parts, respectively mixing with ethyl orthosilicate and ammonia water, magnetically stirring for 10min, gradually dripping ammonia water alcoholic solution into ethyl orthosilicate alcoholic solution, and stirring while dripping (5 min). Heating to 60 deg.C, using ultrasonic oscillator with power of 1200W and frequency of 60KHz, slowly dripping propylene glycol and glycerol in the oscillation process, ultrasonically oscillating for 20min, and stirring for 2 h. Adding fluorine surfactant into the reaction system, and then fully stirring and uniformly mixing to obtain the silicon dioxide nano sol. The method comprises the steps of filling low-pressure pure inert gas into a high-vacuum chamber, putting sodium chloride particles into a high-temperature evaporator, and heating to 1500 ℃ through a heating device to gasify sodium chloride. Sodium chloride vapor was substituted into a liquid nitrogen filled cooling bar by inert gas convection. The produced sodium chloride nanoparticles were collected.

The nursing liquid of the embodiment is prepared according to the following weight parts:

composition (I)	Mass ratio of
		Litista Lifitegrast	1
Polyaminopropylbiguanide PHMB	0.5
		Edetate disodium EDTA-2Na	1
Poloxamer 407	10
		Polyoxyethylene hydrogenated castor oil RH40	3
Hydroxyethylidene diphosphonic acid HYDRAMOL	2
		Hydroxypropyl betacyclodextrin HP-beta-CD	5
Hydroxypropyl methylcellulose HPMC	7
		Propylene glycol	12
Glycerol	24
		Mannitol	20
Sodium chloride	3.4
		Boric acid	16
Tris (hydroxymethyl) aminomethane	13

Soaking hydroxypropyl methylcellulose and hydroxypropyl betacyclodextrin in water for 4-6 hr; adding water into the polyaminopropyl biguanide, edetate disodium, poloxamer, polyoxyethylene hydrogenated castor oil, hydroxyethylidene diphosphonic acid, propylene glycol, treated sodium chloride, boric acid, tris (hydroxymethyl) aminomethane and lithospermate, heating to 50 ℃, and dissolving for later use; and then mixing mannitol and the silicon dioxide nano sol according to the volume ratio of 1:200, putting the mixture into a stirrer, heating to 50 ℃, stirring for 10min, and cooling to room temperature to obtain the care solution.

Example 2:

the preparation material ratio of the silicon dioxide nano sol is as follows: 1 part of ammonia water, 20.9 parts of ethyl orthosilicate, 0.1 part of fluorosurfactant, 78 parts of ethanol, 4 parts of propylene glycol and 5 parts of glycerol;

dividing ethanol into two parts, respectively mixing with ethyl orthosilicate and ammonia water, magnetically stirring for 10min, gradually dripping ammonia water alcoholic solution into ethyl orthosilicate alcoholic solution, and stirring while dripping (5 min). Heating to 60 deg.C, using ultrasonic oscillator with power of 1200W and frequency of 60KHz, slowly dripping propylene glycol and glycerol in the oscillation process, ultrasonically oscillating for 20min, and stirring for 2 h. Adding a fluorine surfactant into the reaction system, and then fully stirring and uniformly mixing to obtain silicon dioxide nano sol; the method comprises the steps of filling low-pressure pure inert gas into a high-vacuum chamber, putting sodium chloride particles into a high-temperature evaporator, and heating to 1500 ℃ through a heating device to gasify sodium chloride. Sodium chloride vapor was substituted into a liquid nitrogen filled cooling bar by inert gas convection. The produced sodium chloride nanoparticles were collected.

The nursing liquid is prepared according to the following mass ratio:

soaking hydroxypropyl methylcellulose and hydroxypropyl betacyclodextrin in water for 4-6 hr; adding water into the polyaminopropyl biguanide, edetate disodium, poloxamer, polyoxyethylene hydrogenated castor oil, hydroxyethylidene diphosphonic acid, propylene glycol, treated sodium chloride, boric acid, tris (hydroxymethyl) aminomethane and lithospermate, heating to 50 ℃, and dissolving for later use; and then mixing mannitol and the silicon dioxide nano sol according to the volume ratio of 1:200, putting the mixture into a stirrer, heating to 50 ℃, stirring for 10min, and cooling to room temperature to obtain the care solution. And (4) filling the care solution, sealing, inspecting by a lamp, and packaging in an inner package.

Example 3.

The preparation material ratio of the silicon dioxide nano sol is as follows: 1.8 percent of ammonia water; 22% of tetraethoxysilane; 0.09% of fluorine surfactant; 77.73% of ethanol; 7 parts of propylene glycol and 4 parts of glycerol;

dividing ethanol into two parts, respectively mixing with ethyl orthosilicate and ammonia water, magnetically stirring for 10min, gradually dripping ammonia water alcoholic solution into ethyl orthosilicate alcoholic solution, and stirring while dripping (5 min). Heating to 60 deg.C, using ultrasonic oscillator with power of 1200W and frequency of 60KHz, slowly dripping propylene glycol and glycerol in the oscillation process, ultrasonically oscillating for 20min, and stirring for 2 h. Adding a fluorine surfactant into the reaction system, and then fully stirring and uniformly mixing to obtain silicon dioxide nano sol; the method comprises the steps of filling low-pressure pure inert gas into a high-vacuum chamber, putting sodium chloride particles into a high-temperature evaporator, and heating to 1600 ℃ through a heating device to gasify sodium chloride. Sodium chloride vapor was substituted into a liquid nitrogen filled cooling bar by inert gas convection. The produced sodium chloride nanoparticles were collected.

The nursing liquid is prepared according to the following mass ratio:

Example 4.

The preparation material ratio of the silicon dioxide nano sol is as follows: 2% of ammonia water; 25% of tetraethoxysilane; 0.1% of fluorine surfactant; 72.9 percent of ethanol; 9 parts of propylene glycol and 10 parts of glycerol;

dividing ethanol into two parts, respectively mixing with ethyl orthosilicate and ammonia water, magnetically stirring for 10min, gradually dripping ammonia water alcoholic solution into ethyl orthosilicate alcoholic solution, and stirring while dripping (5 min). Heating to 60 deg.C, using ultrasonic oscillator with power of 1200W and frequency of 60KHz, slowly dripping propylene glycol and glycerol in the oscillation process, ultrasonically oscillating for 20min, and stirring for 2 h. Adding a fluorine surfactant into the reaction system, and then fully stirring and uniformly mixing to obtain silicon dioxide nano sol; the method comprises the steps of filling low-pressure pure inert gas into a high-vacuum chamber, putting sodium chloride particles into a high-temperature evaporator, and heating to 1600 ℃ through a heating device to gasify sodium chloride. Sodium chloride vapor was substituted into a liquid nitrogen filled cooling bar by inert gas convection. The produced sodium chloride nanoparticles were collected. The nursing liquid is prepared according to the following mass ratio:

Relevant experimental data or figures

1. Retinostat dose selection experiment

Adopting human corneal cell culture, placing RGP into different culture dishes, adding care solution containing different dosages of sitaxel, counting corneal cells after 24h, and respectively setting blank groups (without the care solution), 1% of the sitaxel group, 3% of the sitaxel group, 5% of the sitaxel group, 8% of the sitaxel group and 10% of the sitaxel group. The cell count of each group was calculated based on the cell count of the blank group. The inhibition ratios of the groups are shown in FIG. 1.

According to experimental data, the cell proliferation rate of the sitaxel is increased along with the dosage, and when the dosage reaches 5%, the cell proliferation rate is not changed obviously along with the dosage. Therefore 5% was chosen as the sitagliptin dose.

2. Experiment of drug attachment rate

The nursing liquid prepared by the invention is subjected to a drug attachment rate experiment, RGP is soaked for 12 hours and then taken out, the RGP attached drug is collected, and the attachment rate of the sitaxel and the polyoxyethylene hydrogenated castor oil is calculated. Examples 1-4 are solutions prepared according to the process of the present invention, and the comparative example is otherwise the same as example 1 except that comparative example 1 does not employ silica as the carrier, i.e., an aqueous solution of the solution. The results of the experiment are shown in FIG. 2.

According to the experimental data, the adhesion rate of the water solution of the comparative example, namely the care solution is 18.5 percent of sitaxel and 10.2 percent of polyoxyethylene hydrogenated castor oil; the adhesion rate of the care solution prepared by the embodiments 1-4 is 68.5-66.2% of sitaxel, 82.2-85.5% of polyoxyethylene hydrogenated castor oil, and the adhesion rate of the drug can be obviously improved.

3. Sol congealing point and repeated freeze-thaw test

At normal temperature and normal pressure, the temperature of the samples 1-4 is reduced at a speed of 1 ℃/min, the states of the care solutions of the samples 1-4 are observed, and the test temperature is recorded after the sol is completely condensed. After all the examples are coagulated, the temperature is continuously reduced to-20 ℃, then the temperature is increased at the speed of 1 ℃/min, and after the room temperature is recovered, the examples are observed whether the recovery property is recovered. The temperature rise and fall test was then repeated 10 times and the test results were recorded.

Meanwhile, a comparative example was set, wherein other parameters of comparative example 1 were the same as those of example 1 except that glycerin + propylene glycol was not added, and other parameters of comparative example 2 were the same as those of example 1 except that only glycerin + propylene glycol was added without ultrasonic oscillation, and the experimental results are shown in the following table.

	Setting Point temperature (. degree. C.)	Whether the character is recovered after repeated freeze thawing
			Example 1	-9.2	Is that
Example 2	-9.4	Is that
			Example 3	-8.8	Is that
Example 4	-8.9	Is that
			Comparative example 1	4.8	Whether or not
Comparative example 2	-1.9	Whether or not

From the above experiments, it can be seen that the care solution prepared by the invention has good low temperature resistance and can recover the shape of the care solution.

4. Oxygen transmission rate test

The oxygen transmission rate of RGP after soaking the RGP in the nursing liquid of examples 1-4 for 12h was measured by using a C230M (2019) oxygen transmission rate measuring system, and the measurement results are shown in the following table.

	Oxygen transmission rate (cm)³/(m²·d))
		RGP	423.22
Example 1	408.65
		Example 2	410.55
Example 3	422.88
		Example 4	415.86

From the experimental data, the difference ratio of the oxygen transmission rate of the nursing liquid prepared by the invention after soaking to the oxygen transmission rate of the non-soaked RGP is 1.7-2.8%, which shows that the nursing liquid prepared by the invention has good oxygen transmission rate to the RGP.

5. Safety test of Care solution

5.1 animals

6 New Zealand white rabbits are selected, the body weight is 2.5-3.5 kg, and the female rabbit and the male rabbit are half in each case.

5.2 eye irritation test

Staining with 2% fluorescein sodium 24 hours before experiment, inspecting rabbit eyes with slit lamp, selecting 3 healthy New Zealand white rabbits without any eye disease and inflammation, dripping 0.1ml of nursing solution into conjunctival sac under left eye, passively closing eyes for 2s, using the group as nursing solution group, and dripping equal amount of physiological saline into right eye with the same method, and using the group as normal control group. The rabbit eye was examined for conjunctiva, iris, cornea, etc. 1, 24, 48, and 72 hours after eye dropping using slit lamps and scored according to the following table injury scoring system.

Note: is positive

The rabbit eyes are inspected by a slit lamp before and 1, 24, 48 and 72 hours after the administration of one eye irritation experiment, eye conjunctiva, cornea, iris and other injuries are observed, the irritation reaction scores of the eye conjunctiva, iris and conjunctiva of each animal at each observation time point are added to obtain a total score, and the total score of each group is divided by the total number of the animals to obtain the irritation score. After administration, compared with the normal control group of clinical common eye washing liquid physiological saline, the two groups have no irritation reactions such as eyelid edema, secretion increase and the like at any stage, and the eye irritation score is 0.

5.3 multiple skin irritation experiments

In 3 new zealand white rabbits, 24 hours before the experiment, hairs on both sides of the spine were shaved off with a razor in an area of about 10cm × 15 cm. Taking a plurality of 2.5cm multiplied by 2.5cm sized two-layer gauze blocks, dripping 0.5mL of sample solution into each gauze block for soaking, pasting the gauze blocks on the exposed skin of the rabbit according to the figure 3, pasting care solution (care solution group) on 2 and 6 skins, pasting normal saline (normal control group) on 3 and 5 skins, covering a layer of sealing film and two layers of dry gauze on the gauze blocks, and finally fixing by medical transparent dressing for 6 hours every day for continuous application for 5 days. After each application, the test substance was removed with warm water, and skin reactions were observed at 1 hour, 24 hours, 48 hours, and 72 hours after the removal of the test substance on day 5, and the stimulation intensity was evaluated according to the stimulation reaction type in accordance with the skin reaction scoring system score [1] of section 10 of "biological evaluation of medical instruments" 2005.

After being continuously applied for 5 times, the rabbits of the care solution group and the normal control group have no abnormal performance during the application period, the scores of the care solution group and the normal control group before treatment are both 0, and the skin irritation scores at all time points after application are not significantly different (all P is more than 0.05), which is detailed in the following table.

Group of	n	1h	24h	48h	72h
						Normal control group	3	0.325±0.025	0.335±0.025	0.318±0.025	0.323±0.025
Nursing liquid set	3	0.318±0.052	0.317±0.052	0.320±0.052	0.322±0.052

Experiments prove that the care solution is safe and effective and has no irritation.

Claims

1. A hard corneal contact lens care solution is characterized by comprising the following raw materials in parts by weight: 1-3 parts of sitaxel, 0.5-1.5 parts of poly aminopropyl biguanide, 1-3 parts of edetate disodium, 10-30 parts of poloxamer, 3-9 parts of polyoxyethylene hydrogenated castor oil, 2-6 parts of hydroxyethylidene diphosphonic acid, 5-15 parts of hydroxypropyl betacyclodextrin, 7-21 parts of hydroxypropyl methylcellulose, 10-30 parts of propylene glycol, 10-30 parts of glycerol, 20-60 parts of mannitol, 16-48 parts of boric acid, 3.4-10.2 parts of sodium chloride and 13-39 parts of tris (hydroxymethyl) aminomethane;

the preparation method of the hard corneal contact lens care solution comprises the following steps:

weighing ammonia water, tetraethoxysilane, fluorocarbon surfactant and ethanol in corresponding parts, dividing the ethanol into two uniform parts, respectively mixing the two parts with the tetraethoxysilane and the ammonia water, stirring the mixture by magnetic force for 10min, gradually dripping the alcohol solution of the ammonia water into the alcohol solution of the tetraethoxysilane, and stirring the mixture for 5min while dripping; heating to 60 ℃, adopting an ultrasonic oscillator with the power of 1200W and the frequency of 60KHz, slowly dripping propylene glycol and glycerol in the oscillation process, carrying out ultrasonic oscillation for 20min, stirring for 2h, adding a fluorine surfactant into a reaction system, and fully stirring and uniformly mixing to obtain silicon dioxide nano sol; filling low-pressure pure inert gas into a high-vacuum chamber, placing sodium chloride particles into a high-temperature evaporator, heating to 1500 ℃ by a heating device to gasify sodium chloride, bringing sodium chloride steam into a cooling rod filled with liquid nitrogen by inert gas convection, and collecting the generated sodium chloride nanoparticles; mixing the raw materials with the silica nano sol to prepare a care solution;

the preparation method of the care solution comprises the following specific steps:

2. The method for preparing a hard corneal contact lens care solution as claimed in claim 1, wherein the silica nanosol is prepared from the following materials: 1-2 parts of ammonia water, 15-25 parts of ethyl orthosilicate, 0.01-0.1 part of fluorosurfactant, 78-88 parts of ethanol, 3-10 parts of propylene glycol and 3-10 parts of glycerol.

3. The method for preparing a hard corneal contact lens solution as defined in claim 1, wherein the solution obtained is treated by an ultrafiltration device having a pore size of 100A °.

4. The method for preparing a hard corneal contact lens care solution as claimed in claim 1, wherein the silica nanosol is used as a carrier solution for the hard corneal contact lens care solution.