Long-acting moisturizing contact lens lubricating liquid and preparation method thereof

Abstract

The invention belongs to the technical field of invisible eye care, and discloses a long-acting moisturizing contact lens lubricating liquid and a preparation method thereof. The contact lens lubricating liquid is prepared from the following components in percentage by mass: 0.05 to 0.2 percent of sodium hyaluronate, 0.1 to 0.5 percent of trehalose, 0.5 to 1.5 percent of polyethylene glycol diglycidyl ether, 0.3 to 0.8 percent of hydroxypropyl methylcellulose, 2 to 3 percent of poloxamer 407, 0.6 to 0.9 percent of sodium chloride, 0.0001 to 0.0005 percent of polyhexamethylene biguanide, 0.1 to 1.2 percent of chondroitin sulfate and the balance of phosphate buffer solution. The raw material components have a synergistic effect, so that the moisturizing duration can be effectively prolonged, the antibacterial efficiency is improved, and the friction coefficient is reduced. The moisturizing duration of the prepared contact lens lubricating liquid can reach 11.2 h, the minimum friction coefficient can be 0.04, and the wearing comfort of contact lenses can be improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a long-acting moisturizing contact lens lubricant and a preparation method thereof. BACKGROUND

[0002] With the popularization and application of contact lenses, the performance optimization of lubricant, as a key care product for maintaining lens moisture and wearing comfort, has been increasingly valued by the industry. However, the contact lens lubricant in the prior art still has the following technical problems to be solved:

[0003] Firstly, in terms of moisturizing performance, traditional lubricants generally use a single moisturizing component (such as hydroxyethyl cellulose or polyvinyl alcohol), which has a short moisturizing duration, and users need to frequently instill, which seriously affects the convenience of use. Although the moisturizing time can be prolonged by increasing the concentration of high molecular materials, it will result in too high viscosity of the solution, which destroys the physiological osmotic pressure of the tear fluid and may cause adverse reactions such as corneal edema.

[0004] Secondly, in terms of biocompatibility, the preservatives commonly used in commercial products (such as benzalkonium chloride) have obvious toxicity to corneal epithelial cells (in vitro experiments show that the cell survival rate is <80%), and long-term use may aggravate the symptoms of dry eyes. At the same time, the conventional formula lacks the repair function for corneal micro-damage caused by long-term wearing, and cannot meet the health needs of modern contact lens users.

[0005] Therefore, it is of great significance to research a contact lens lubricant with long-acting moisturizing effect and good biocompatibility and a preparation method thereof. SUMMARY

[0006] The present application provides a long-acting moisturizing contact lens lubricant and a preparation method thereof, which aims to solve the problem of short moisturizing time and frequent instillation of the contact lens lubricant in the prior art.

[0007] In order to achieve the above-mentioned application purpose, the present application provides the following technical solutions:

[0008] The present application provides a long-acting moisturizing contact lens lubricant, which is composed of the following components with mass fraction:

[0009] Sodium hyaluronate 0.05-0.2%, trehalose 0.1-0.5%, polyethylene glycol diglycidyl ether 0.5-1.5%, hydroxypropyl methyl cellulose 0.3-0.8%, poloxamer 407 2-3%, sodium chloride 0.6-0.9%, polyhexamethylene biguanide 0.0001-0.0005%, chondroitin sulfate 0.1-1.2%, and the balance is phosphate buffer.

[0010] Preferably, the concentration of the phosphate in the phosphate buffer is 0.01-0.03M;

[0011] The pH value of the phosphate buffer is 6.8-7.2.

[0012] Preferably, the molecular weight of the hypromellose is 20000-100000.

[0013] The application further provides a preparation method of the long-acting moisturizing contact lens lubricant, comprising the following preparation steps:

[0014] 1) mixing the phosphate buffer with the hypromellose to obtain a hypromellose solution;

[0015] 2) mixing the hypromellose solution, the pre-swollen poloxamer 407, the sodium hyaluronate, the chondroitin sulfate, the trehalose, the polyethylene glycol diglycidyl ether and the sodium chloride to obtain a mixed solution;

[0016] 3) adding the polyhexamethylene biguanide into the mixed solution, and filtering to obtain the contact lens lubricant.

[0017] Preferably, in the step 1), the temperature of the mixing is 48-55℃, the mixing time is 50-60min, and the mixing speed is 7000-8000rpm.

[0018] Preferably, in the step 2), the pre-swelling temperature of the poloxamer 407 is 0-4℃, and the pre-swelling time is 3-5h.

[0019] Preferably, in the step 2), the temperature of the mixing is 38-42℃, the mixing time is 30-50min, and the mixing speed is 200-300rpm.

[0020] Preferably, in the step 3), the temperature of the mixed solution is 20-30℃.

[0021] Preferably, in the step 3), the filter membrane is a polyvinylidene fluoride membrane, and the pore size of the polyvinylidene fluoride membrane is 0.2-0.25μm.

[0022] According to the above technical solution, compared with the prior art, the application has the following beneficial effects:

[0023] The raw material components in the application have a synergistic effect, which can effectively prolong the moisturizing time, improve the bacteriostatic efficiency and reduce the friction coefficient. The moisturizing time of the prepared contact lens lubricant can be up to 11.2h, the bacteriostatic rate is 99.99%, and the friction coefficient can be as low as 0.04, which can improve the comfort of wearing the contact lens. DETAILED DESCRIPTION

[0024] The application provides a long-acting moisturizing contact lens lubricant, which is composed of the following components in mass fraction:

[0025] Sodium hyaluronate 0.05-0.2%, trehalose 0.1-0.5%, polyethylene glycol diglycidyl ether 0.5-1.5%, hydroxypropyl methyl cellulose 0.3-0.8%, poloxamer 407 2-3%, sodium chloride 0.6-0.9%, polyhexamethylene biguanide 0.0001-0.0005%, chondroitin sulfate 0.1-1.2%, and the rest is phosphate buffer.

[0026] In the application, the mass fraction of sodium hyaluronate is preferably 0.08-0.18%, further preferably 0.1-0.16%, and more preferably 0.12-0.15%; the mass fraction of trehalose is preferably 0.2-0.4%, and further preferably 0.3%; the mass fraction of polyethylene glycol diglycidyl ether is preferably 0.7-1.3%, further preferably 0.8-1.2%, and more preferably 1-1.1%; the mass fraction of hydroxypropyl methyl cellulose is preferably 0.4-0.7%, further preferably 0.5-0.6%; the mass fraction of poloxamer 407 is preferably 2.2-2.8%, further preferably 2.3-2.6%, and more preferably 2.4-2.5%; the mass fraction of sodium chloride is preferably 0.65-0.85%, further preferably 0.7-0.8%, and more preferably 0.75%; the mass fraction of polyhexamethylene biguanide is preferably 0.0002-0.0004%, and further preferably 0.0003%; and the mass fraction of chondroitin sulfate is preferably 0.3-1%, further preferably 0.5-0.8%, and more preferably 0.6-0.7%.

[0027] In the application, the concentration of phosphate in the phosphate buffer is preferably 0.01-0.03M, further preferably 0.015-0.025M, and more preferably 0.02-0.022M.

[0028] The pH value of the phosphate buffer is preferably 6.8-7.2, further preferably 6.9-7.1, and more preferably 7.

[0029] In the application, the total concentration of phosphate is controlled to be 0.01-0.03M, which can avoid ion aggregation with poloxamer 407, thereby ensuring the stability of the temperature-sensitive gel.

[0030] In the application, the molecular weight of the hydroxypropyl methyl cellulose is preferably 20000-100000, further preferably 40000-80000, and more preferably 50000-60000.

[0031] In the application, sodium hyaluronate locks up moisture through hydrogen bond network, reduces the friction coefficient between the lens and the cornea, and can form a moisturizing network with trehalose to improve the moisture retention rate at 35 DEG C (i.e. body temperature), and enhance the temperature-sensitive response through the synergistic effect of poloxamer 407.

[0032] In the application, polyethylene glycol diglycidyl ether can prolong the wetting time; the hydroxypropyl methyl cellulose as a film forming agent can form a hydrophilic protective layer on the surface of the contact lens, thereby prolonging the wetting time, and can synergistically stabilize the osmotic pressure with sodium chloride.

[0033] In the application, the poloxamer 407 can reduce friction and enhance the comfort of wearing contact lenses; the polyhexamethylene biguanide enhances the antibacterial performance of the contact lens lubricating liquid; the chondroitin sulfate can inhibit the activity of hyaluronic acid sodium enzyme, thereby prolonging the moisturizing time.

[0034] The application also provides a preparation method of the long-acting moisturizing contact lens lubricating liquid, comprising the following preparation steps:

[0035] 1) mixing the phosphate buffer solution with the hydroxypropyl methyl cellulose to obtain a hydroxypropyl methyl cellulose solution;

[0036] 2) mixing the hydroxypropyl methyl cellulose solution, the pre-swollen poloxamer 407, the sodium hyaluronate, the chondroitin sulfate, the trehalose, the polyethylene glycol diglycidyl ether and the sodium chloride to obtain a mixed solution;

[0037] 3) adding the polyhexamethylene biguanide to the mixed solution, and filtering to obtain the contact lens lubricating liquid.

[0038] In the application, in step 1), the mixing temperature is preferably 48-55 DEG C, further preferably 50-54 DEG C, and more preferably 52-53 DEG C, the mixing time is preferably 50-60 min, further preferably 52-58 min, and more preferably 54-56 min, and the mixing speed is preferably 7000-8000 rpm, further preferably 7200-7800 rpm, and more preferably 7500-7600 rpm.

[0039] In the application, in step 2), the pre-swelling temperature of the poloxamer 407 is preferably 0-4 DEG C, further preferably 1-3 DEG C, and more preferably 2 DEG C, and the pre-swelling time is preferably 3-5 h, further preferably 3.5-4.5 h, and more preferably 4 h.

[0040] In the present application, in the step 2), the temperature of the mixing is preferably 38-42℃, further preferably 39-41℃, more preferably 40℃, the mixing time is preferably 30-50min, further preferably 35-45min, more preferably 40-42min, and the rotation speed of the mixing is preferably 200-300rpm, further preferably 220-280rpm, more preferably 240-250rpm.

[0041] In the present application, in the step 3), the temperature of the mixed solution is preferably 20-30℃, further preferably 22-28℃, more preferably 25-26℃.

[0042] In the present application, in the step 3), the filter membrane is preferably a polyvinylidene fluoride membrane, and the pore size of the polyvinylidene fluoride membrane is preferably 0.2-0.25μm, further preferably 0.21-0.24μm, more preferably 0.22-0.23μm.

[0043] In the present application, in the step 3), the purpose of the filtration is to further remove bacteria.

[0044] The technical solutions provided by the present application will be described in detail below in combination with the examples, but they should not be understood as limiting the scope of protection of the present application.

[0045] Example 1

[0046] In the present example, the raw material components and their mass fractions are as follows:

[0047] sodium hyaluronate 0.05%, trehalose 0.1%, polyethylene glycol diglycidyl ether 0.5%, hydroxypropyl methyl cellulose with a molecular weight of 20000 0.3%, poloxamer 407 2%, sodium chloride 0.6%, polyhexamethylene biguanide 0.0001%, chondroitin sulfate 0.1%, and the rest is phosphate buffer solution (pH 7.2, total phosphate concentration 0.01M, molar ratio of sodium dihydrogen phosphate to disodium hydrogen phosphate 0.9:1.1);

[0048] Preparation of the long-acting moisturizing contact lens lubricating solution in the present example:

[0049] Mix the phosphate buffer solution and hydroxypropyl methyl cellulose at 50℃ and a rotation speed of 7000rpm for 60min to obtain a hydroxypropyl methyl cellulose solution;

[0050] Pre-swelling of poloxamer 407 at 3℃ for 4h to obtain pre-swollen poloxamer 407;

[0051] The poloxamer 407, sodium hyaluronate, chondroitin sulfate, trehalose, polyethylene glycol diglycidyl ether and sodium chloride pre-swollen were sequentially added to the hydroxypropyl methyl cellulose solution at 40°C and 250 rpm, and the mixture was mixed for 45 min to obtain a mixed solution;

[0052] The mixed solution was cooled to 25°C, and then polyhexamethylene biguanide was added and mixed, and then filtered through a polyvinylidene fluoride membrane with a pore size of 0.22 μm to obtain a contact lens lubricating solution.

[0053] Example 2

[0054] The raw material components and their mass fractions in Example 1 were replaced with "sodium hyaluronate 0.12%, trehalose 0.3%, polyethylene glycol diglycidyl ether 1%, hydroxypropyl methyl cellulose with a molecular weight of 20000 0.55%, poloxamer 407 2.5%, sodium chloride 0.75%, polyhexamethylene biguanide 0.0003%, chondroitin sulfate 0.65%, and the balance was a phosphate buffer solution with a pH value of 7.2 and a total phosphate concentration of 0.01M (the molar ratio of sodium dihydrogen phosphate and disodium hydrogen phosphate was 0.9:1.1)", and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0055] Example 3

[0056] The raw material components and their mass fractions in Example 1 were replaced with "sodium hyaluronate 0.2%, trehalose 0.5%, polyethylene glycol diglycidyl ether 1.5%, hydroxypropyl methyl cellulose with a molecular weight of 20000 0.8%, poloxamer 407 3%, sodium chloride 0.9%, polyhexamethylene biguanide 0.0005%, chondroitin sulfate 1.2%, and the balance was a phosphate buffer solution with a pH value of 7.2 and a total phosphate concentration of 0.01M (the molar ratio of sodium dihydrogen phosphate and disodium hydrogen phosphate was 0.9:1.1)", and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0057] Example 4

[0058] The raw material components and their mass fractions in Example 1 were replaced with "sodium hyaluronate 0.08%, trehalose 0.2%, polyethylene glycol diglycidyl ether 0.8%, hydroxypropyl methyl cellulose with a molecular weight of 20000 0.4%, poloxamer 407 2.2%, sodium chloride 0.7%, polyhexamethylene biguanide 0.0002%, chondroitin sulfate 0.3%, and the balance was a phosphate buffer solution with a pH value of 7.2 and a total phosphate concentration of 0.01M (the molar ratio of sodium dihydrogen phosphate and disodium hydrogen phosphate was 0.9:1.1)", and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0059] Example 5

[0060] The raw material components and their mass fractions in Example 1 were replaced with "sodium hyaluronate 0.15%, trehalose 0.4%, polyethylene glycol diglycidyl ether 1.2%, hydroxypropyl methyl cellulose with a molecular weight of 20000 0.7%, poloxamer 407 2.8%, sodium chloride 0.85%, polyhexamethylene biguanide 0.0004%, chondroitin sulfate 0.9%, and the balance was a phosphate buffer with a pH value of 7.2 and a total phosphate concentration of 0.01M (wherein the molar ratio of sodium dihydrogen phosphate and disodium hydrogen phosphate was 0.9:1.1)", and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0061] Comparative Example 1

[0062] The "poloxamer 407" in Example 1 was deleted, and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0063] Comparative Example 2

[0064] The "polyethylene glycol diglycidyl ether" in Example 1 was deleted, and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0065] Comparative Example 3

[0066] The "balance was a phosphate buffer with a pH value of 7.2 and a phosphate concentration of 0.01M" in Example 1 was replaced with "balance was a phosphate buffer with a pH value of 6.5 and a phosphate concentration of 0.01M", and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0067] Comparative Example 4

[0068] The "mixing the phosphate buffer and hydroxypropyl methyl cellulose at 50°C at a speed of 7000 rpm for 60 min" in Example 1 was replaced with "mixing the phosphate buffer and hydroxypropyl methyl cellulose at 30°C at a speed of 7000 rpm for 60 min", and the other steps were the same as in Example 1 to obtain a contact lens lubricating solution.

[0069] The contact lens lubricating solutions obtained in Examples 1-5 and Comparative Examples 1-4 were respectively subjected to the following performance tests, and the test results are shown in Table 1.

[0070] Moisture retention time: 3 drops of contact lens lubricating solution were added to the surface of a contact lens, and the moisture retention time was counted under the condition of 35°C and 50% RH;

[0071] Bacteriostatic rate:

[0072] Preparation of bacterial suspension: take the test tubes of Staphylococcus aureus, Escherichia coli and Candida albicans stored at -20℃, thaw them at 37℃, and after complete thawing, transfer the thawed liquid into a 15mL centrifuge tube with a sterile disposable pipette, add the corresponding medium, and subculture overnight at 37℃. The next day, centrifuge the bacterial suspension at 3000rpm for 5min, add phosphate buffer and mix well, repeat the above operation, and finally dilute with sterile PBS to obtain a final concentration of about 10 5 cfu / m.

[0073] Test procedure: take three sterile 15mL test tubes, add an appropriate amount of the contact lens lubricant to be tested, add 500μL of the prepared bacterial suspension, mix well with a sterile disposable pipette, and after 4h, mix the solution well with a pipette, then take 100μL of the mixed solution and inoculate it into an appropriate amount of nutrient agar medium (for Staphylococcus aureus and Escherichia coli) and Sabouraud medium (for Candida albicans). Make two plates for each tube, and incubate at 35℃ for three days. Calculate the inhibition rate by viable cell counting method.

[0074] Inhibition rate (LR) = [Log 10 (I) - Log 10 (F)]

[0075] Wherein, I is the number of colonies of the control group, and F is the number of colonies after exposure to the solution to be tested.

[0076] Friction coefficient: according to the four-ball method of GB3142-90, the friction coefficient is measured by a four-ball friction and wear tester, with a friction system load of 30N and a ceramic ball diameter of 12.7mm. The experimental conditions are set as follows: rotation speed 1500r / min, temperature 37℃, and test time 30min.

[0077] Table 1: performance test results of the contact lens lubricant obtained in Examples 1-5 and Comparative Examples 1-4

[0078]

[0079]

[0080] As shown in Table 1, the moisturizing duration of the contact lens lubricant prepared by the present application can be as long as 11.2h, which is much longer than the 4.8h of the lubricants obtained in Comparative Examples 1-4. The inhibition rate of the lubricants obtained in Examples 1-5 against Staphylococcus aureus, Escherichia coli and Candida albicans can reach 99.99%, and the friction coefficient of the lubricants obtained in Examples 1-5 can be as low as 0.04, which can improve the comfort of wearing contact lenses.

[0081] The above merely describes the preferred embodiments of the present application, and it should be pointed out that, for those skilled in the art, several improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as falling within the protection scope of the present application.

Claims

1. A long-lasting moisturizing contact lens lubricant, characterized in that, It consists of components with the following mass fractions: Sodium hyaluronate 0.05-0.2%, trehalose 0.1-0.5%, polyethylene glycol diglycidyl ether 0.5-1.5%, hydroxypropyl methylcellulose 0.3-0.8%, poloxamer 407 2-3%, sodium chloride 0.6-0.9%, polyhexamethylene biguanide 0.0001-0.0005%, chondroitin sulfate 0.1-1.2%, with the balance being phosphate buffer.

2. The long-lasting moisturizing contact lens lubricant according to claim 1, characterized in that, The concentration of phosphate in the phosphate buffer solution is 0.01–0.03 M; The pH value of the phosphate buffer solution is 6.8 to 7.

2.

3. The long-lasting moisturizing contact lens lubricant according to claim 1, characterized in that, The molecular weight of the hydroxypropyl methylcellulose is 20,000 to 100,000.

4. A method for preparing a long-lasting moisturizing contact lens lubricant according to any one of claims 1 to 3, characterized in that, The preparation steps include the following: 1) Mix phosphate buffer with hydroxypropyl methylcellulose to obtain a hydroxypropyl methylcellulose solution; 2) Mix hydroxypropyl methylcellulose solution, pre-swollen poloxamer 407, sodium hyaluronate, chondroitin sulfate, trehalose, polyethylene glycol diglycidyl ether and sodium chloride to obtain a mixture; 3) Add polyhexamethylene biguanide to the mixture, filter, and obtain contact lens lubricant.

5. The method for preparing a long-lasting moisturizing contact lens lubricant according to claim 4, characterized in that, In step 1), the mixing temperature is 48-55℃, the mixing time is 50-60 min, and the mixing speed is 7000-8000 rpm.

6. The method for preparing a long-lasting moisturizing contact lens lubricant according to claim 5, characterized in that, In step 2), the pre-swelling temperature of poloxamer 407 is 0-4°C, and the pre-swelling time is 3-5 hours.

7. The method for preparing a long-lasting moisturizing contact lens lubricant according to claim 6, characterized in that, In step 2), the mixing temperature is 38–42°C, the mixing time is 30–50 min, and the mixing speed is 200–300 rpm.

8. A method for preparing a long-lasting moisturizing contact lens lubricant according to claim 6 or 7, characterized in that, In step 3), the temperature of the mixture is 20-30°C.

9. The method for preparing a long-lasting moisturizing contact lens lubricant according to claim 8, characterized in that, In step 3), the filtered membrane is a polyvinylidene fluoride membrane with a pore size of 0.2 to 0.25 μm.

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