Temperature-sensitive contact lens eye moistening gel and preparation method thereof

Abstract

The invention belongs to the technical field of contact lens care, and provides temperature-sensitive contact lens eye-moistening gel and a preparation method thereof. The temperature-sensitive contact lens eye-moistening gel is prepared from the following raw materials in parts by mass: a gel matrix, a surfactant, an osmotic pressure regulator, an active component, a chelating agent, a buffering agent and the balance of injection water, the composition of the gel matrix is defined. Chitosan, sodium hyaluronate and polyvinyl alcohol are compounded to serve as a gel matrix, a polyelectrolyte compound is formed, gelation time is shortened, gel strength and swelling resistance are improved, biocompatibility is improved, and drug-loaded delivery of active ingredients is achieved; the gel matrix and the surfactant are reasonably selected, the viscosity of the solution is increased, the gelation time is shortened, the excellent effect of relieving eye fatigue and dryness is achieved, the wearing comfort of the contact lens is remarkably improved, and the oxygen permeation effect of the contact lens is not obviously reduced after gel forming.

Description

Technical Field

[0001] This invention relates to the field of contact lens care technology, and in particular to a temperature-sensitive contact lens moisturizing gel and its preparation method. Background Technology

[0002] Contact lenses have become a substitute for eyeglasses, primarily used to correct vision defects. Their convenience has made them popular with consumers. However, during wear, protein deposits and metabolic waste products can accumulate, causing discomfort and potentially damaging the eyes in extreme conditions. Contact lens eye drops / gels are eye care products specifically designed for contact lens wearers, primarily used to relieve discomfort such as dryness and fatigue caused by prolonged contact lens wear. Most eye drops on the market are hormone- or antibiotic-based, and improper use can cause irreversible eye damage. Eye gels, due to their sustained drug release, are favored by contact lens wearers. While liquid at room temperature, eye gels transform into a gel upon application to the eye, achieving local retention and sustained release. Active pharmaceutical ingredients can be delivered to the eye through the eye gel for controlled and continuous release.

[0003] Eye-moisturizing gels typically use poloxamer as the gel matrix, supplemented with osmotic pressure regulators, surfactants, and other auxiliary agents, as well as corresponding active pharmaceutical ingredients, to achieve eye moisturizing, eye protection, and delivery of specific medications. For contact lens wearers, eye-moisturizing gels need to offer diverse functions, such as long-lasting hydration to reduce friction between the contact lens and the cornea; shortened gel formation time for longer drug action; maintaining corneal surface osmotic pressure balance; reducing mechanical irritation of the eyelids from the contact lens edge to minimize foreign body sensation; and maintaining high oxygen permeability after gel formation, among other things. Currently, eye-moisturizing gels are not comprehensive in their functions; while maintaining long-lasting lubrication, they sacrifice some drug release and oxygen permeability, resulting in a less than ideal experience for contact lens wearers.

[0004] Therefore, developing eye-moisturizing gels suitable for contact lenses to comprehensively improve the wearer's experience is a direction for ongoing research. Summary of the Invention

[0005] The purpose of this invention is to provide a temperature-sensitive contact lens moisturizing gel and its preparation method, addressing the shortcomings of existing technologies.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a temperature-sensitive contact lens moisturizing gel, which, by mass fraction, comprises the following ingredients:

[0008] The composition consists of 3-8% gel matrix, 0.3-3% surfactant, 0.2-1% osmotic pressure regulator, 2-6% active ingredient, 0.05-2% chelating agent, 0.03-1% buffer, and the balance being water for injection.

[0009] The gel matrix contains chitosan, sodium hyaluronate, and polyvinyl alcohol.

[0010] Preferably, the mass ratio of chitosan, sodium hyaluronate, and polyvinyl alcohol is 0.5–3:0.5–5:1.

[0011] Preferably, the active ingredient comprises an active pharmaceutical ingredient and / or a nutritional ingredient;

[0012] The active pharmaceutical ingredient includes one or more of cyclosporine A, acyclovir, sodium hyaluronate, and carbomer;

[0013] The nutrients include plant extracts.

[0014] Preferably, the surfactant comprises one or more of polyvinylpyrrolidone, sodium dodecyl sulfonate, and poloxamer.

[0015] Preferably, the osmotic pressure regulator comprises one or more of sodium chloride, potassium chloride, and calcium chloride;

[0016] The chelating agent comprises one or more of sodium alginate, sodium ethylenediaminetetraacetate, and sodium hexametaphosphate;

[0017] The buffer contains one or more of borates, citrates, acetates, and carbonates.

[0018] This invention also provides a method for preparing the aforementioned temperature-sensitive contact lens lubricating gel, comprising the following steps:

[0019] 1) Mix chitosan, sodium hyaluronate, polyvinyl alcohol and water for injection in part 1, and stir to obtain a gel matrix solution;

[0020] 2) Mix the surfactant, osmotic pressure regulator, active ingredient, chelating agent, buffer, and second-part injection water, and stir to obtain a mixture;

[0021] 3) Add the mixture to the gel matrix solution and stir to obtain the thermosensitive contact lens moisturizing gel.

[0022] Preferably, the mass ratio of the first part of the injected water to the second part of the injected water is 1:2 to 4.

[0023] Preferably, the stirring speed in step 1) is 100-200 rpm and the stirring time is 20-40 min.

[0024] Preferably, the stirring speed in step 2) is 300-500 rpm and the stirring time is 30-60 min.

[0025] Preferably, the stirring speed in step 3) is 500-800 rpm and the stirring time is 20-40 min.

[0026] The beneficial effects of this invention are:

[0027] 1) This invention uses chitosan, sodium hyaluronate, and polyvinyl alcohol as a gel matrix. The electrostatic interaction between anions and cations allows the positively charged chitosan and the negatively charged sodium hyaluronate to form a polyelectrolyte complex, shortening the gelation time. Polyvinyl alcohol increases the degree of physical cross-linking of the system, improving gel strength and anti-swelling ability. Chitosan itself has analgesic, anti-inflammatory, and antibacterial effects, while sodium hyaluronate promotes the retention and exchange of tears on the corneal surface. The combined use of chitosan, sodium hyaluronate, and polyvinyl alcohol improves biocompatibility and enables drug delivery of active ingredients.

[0028] 2) Using the gel matrix of the present invention, the viscosity of the solution is increased and the gelation time is shortened under the action of surfactants;

[0029] 3) This invention prepares a temperature-sensitive contact lens moisturizing gel by rationally selecting gel matrix and surfactant, and supplementing it with osmotic pressure regulator, chelating agent and buffer. It can form a gel quickly and has excellent effects on relieving eye fatigue and dryness, significantly improving the comfort of wearing contact lenses. Moreover, the gel does not cause a significant decrease in the oxygen permeability of contact lenses after gel formation. The chelating agent can bind metal ions and improve protein deposition. Detailed Implementation

[0030] This invention provides a temperature-sensitive contact lens moisturizing gel, which, by mass fraction, comprises the following ingredients:

[0031] The composition consists of 3-8% gel matrix, 0.3-3% surfactant, 0.2-1% osmotic pressure regulator, 2-6% active ingredient, 0.05-2% chelating agent, 0.03-1% buffer, and the balance being water for injection.

[0032] The gel matrix contains chitosan, sodium hyaluronate, and polyvinyl alcohol.

[0033] In this invention, the temperature-sensitive contact lens moisturizing gel comprises, by mass fraction, the following ingredients:

[0034] The gel matrix comprises 3-8%, preferably 4-7%, more preferably 5-6%; surfactant comprises 0.3-3%, preferably 0.8-2.5%, more preferably 1-2%, and more preferably 1.5%; osmotic pressure regulator comprises 0.2-1%, preferably 0.5-0.8%, more preferably 0.6-0.7%; active ingredient comprises 2-6%, preferably 3-5%, more preferably 3.5-4.5%, and more preferably 4%; chelating agent comprises 0.05-2%, preferably 0.1-1.8%, more preferably 0.5-1.2%, and more preferably 0.7-1%; buffer comprises 0.03-1%, preferably 0.1-0.8%, more preferably 0.25-0.65%, and more preferably 0.4-0.5%; and the balance is water for injection.

[0035] In this invention, the injection water is preferably sterile water.

[0036] In this invention, the mass ratio of chitosan, sodium hyaluronate and polyvinyl alcohol is preferably 0.5-3:0.5-5:1, more preferably 1-2.5:1.5-4:1, and even more preferably 1.5-2:2-3:1.

[0037] In this invention, the molecular weight of the chitosan is preferably 30,000 to 100,000, and more preferably 50,000 to 80,000;

[0038] The molecular weight of the sodium hyaluronate is preferably 500,000 to 1,000,000, and more preferably 600,000 to 800,000;

[0039] The molecular weight of the polyvinyl alcohol is preferably 20,000 to 70,000, and more preferably 40,000 to 50,000.

[0040] In this invention, the active ingredient preferably comprises an active pharmaceutical ingredient and / or a nutritional ingredient;

[0041] The active pharmaceutical ingredient preferably includes one or more of cyclosporine A, acyclovir, sodium hyaluronate, and carbomer;

[0042] The nutrients preferably include plant extracts.

[0043] In this invention, the plant extract preferably includes one or more of the following: peony extract, aloe extract, perilla extract, and cassia seed extract.

[0044] In this invention, the surfactant preferably comprises one or more of polyvinylpyrrolidone, sodium dodecyl sulfonate, and poloxamer.

[0045] In this invention, the osmotic pressure regulator preferably comprises one or more of sodium chloride, potassium chloride, and calcium chloride;

[0046] The chelating agent preferably comprises one or more of sodium alginate, sodium ethylenediaminetetraacetate, and sodium hexametaphosphate;

[0047] The buffer preferably comprises one or more of borates, citrates, acetates, and carbonates.

[0048] In this invention, the borate is preferably sodium borate, the citrate is preferably sodium citrate, the acetate is preferably sodium acetate, and the carbonate is preferably sodium carbonate.

[0049] This invention also provides a method for preparing the aforementioned temperature-sensitive contact lens lubricating gel, comprising the following steps:

[0050] 1) Mix chitosan, sodium hyaluronate, polyvinyl alcohol and water for injection in part 1, and stir to obtain a gel matrix solution;

[0051] 2) Mix the surfactant, osmotic pressure regulator, active ingredient, chelating agent, buffer, and second-part injection water, and stir to obtain a mixture;

[0052] 3) Add the mixture to the gel matrix solution and stir to obtain the thermosensitive contact lens moisturizing gel.

[0053] In this invention, the mass ratio of the first part of the injectable water to the second part of the injectable water is preferably 1:2 to 4, more preferably 1:2.5 to 3.5, and even more preferably 1:3.

[0054] In this invention, the stirring speed in step 1) is preferably 100-200 rpm, more preferably 120-180 rpm, and even more preferably 150 rpm; the stirring time is preferably 20-40 min, more preferably 25-35 min, and even more preferably 30 min.

[0055] In this invention, the stirring speed in step 2) is preferably 300-500 rpm, more preferably 350-450 rpm, and even more preferably 400 rpm; the stirring time is preferably 30-60 min, more preferably 40-50 min, and even more preferably 45 min.

[0056] In this invention, the stirring speed in step 3) is preferably 500-800 rpm, more preferably 600-700 rpm, and even more preferably 650 rpm; the stirring time is preferably 20-40 min, more preferably 25-35 min, and even more preferably 30 min.

[0057] In this invention, it is preferable to perform sterilization treatment after stirring in step 1), after stirring in step 2), and after stirring in step 3.

[0058] The sterilization process is preferably membrane filtration sterilization.

[0059] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0060] In the embodiments and comparative examples of the present invention, the osmotic pressure regulator is sodium chloride, the chelating agent is sodium ethylenediaminetetraacetate, the buffer is sodium citrate, and the injection water is sterile water.

[0061] Example 1

[0062] A temperature-sensitive contact lens moisturizing gel, by mass fraction, is made from the following raw materials:

[0063] The composition consists of 5% gel matrix, 3% surfactant, 0.2% osmotic pressure regulator, 4% active ingredient, 0.7% chelating agent, 0.03% buffer, and the remainder is water for injection.

[0064] The gel matrix consists of chitosan, sodium hyaluronate, and polyvinyl alcohol in a mass ratio of 1.5:0.5:1. The molecular weight of chitosan is 50,000, that of sodium hyaluronate is 500,000, and that of polyvinyl alcohol is 40,000. The surfactant is polyvinylpyrrolidone with a molecular weight of 50,000, and the active ingredient is peony extract.

[0065] Preparation method of thermosensitive contact lens moisturizing gel: Chitosan, sodium hyaluronate, polyvinyl alcohol, and water for injection (part 1) are mixed and stirred at 150 rpm for 30 min. The mixture is then sterilized through a 0.22 μm polyvinylidene fluoride (PVDF) filter membrane to obtain a gel matrix solution. Surfactant, osmotic pressure regulator, active ingredient, chelating agent, buffer, and water for injection (part 2) are mixed and stirred at 300 rpm for 60 min. The mixture is then sterilized through a 0.22 μm PVDF filter membrane to obtain a mixed solution. This mixed solution is added to the gel matrix solution and stirred at 800 rpm for 20 min. The mixture is then sterilized through a 0.22 μm PVDF filter membrane to obtain the thermosensitive contact lens moisturizing gel. The mass ratio of water for injection (part 1) to water for injection (part 2) is 1:3.

[0066] Example 2

[0067] The mass ratio of chitosan, sodium hyaluronate, and polyvinyl alcohol in Example 1 was modified to 3:2:1, while other aspects remained the same as in Example 1.

[0068] Example 3

[0069] The mass ratio of chitosan, sodium hyaluronate, and polyvinyl alcohol in Example 1 was modified to 0.5:5:1, while other aspects remained the same as in Example 1.

[0070] Example 4

[0071] The surfactant in Example 1 was replaced with sodium dodecyl sulfonate.

[0072] Example 5

[0073] A temperature-sensitive contact lens moisturizing gel, by mass fraction, is made from the following raw materials:

[0074] The composition consists of 3% gel matrix, 1.5% surfactant, 0.6% osmotic pressure regulator, 2% active ingredient, 2% chelating agent, 0.4% buffer, and the remainder is water for injection.

[0075] The gel matrix consists of chitosan, sodium hyaluronate, and polyvinyl alcohol in a mass ratio of 1.5:0.5:1. The molecular weight of chitosan is 100,000, that of sodium hyaluronate is 700,000, and that of polyvinyl alcohol is 20,000. The surfactant is sodium dodecyl sulfonate, and the active ingredient is sodium hyaluronate.

[0076] The preparation method of the thermosensitive contact lens moisturizing gel is the same as in Example 1.

[0077] Example 6

[0078] A temperature-sensitive contact lens moisturizing gel, by mass fraction, is made from the following raw materials:

[0079] The composition consists of 8% gel matrix, 0.3% surfactant, 1% osmotic pressure regulator, 6% active ingredient, 0.05% chelating agent, 1% buffer, and the remainder is water for injection.

[0080] The gel matrix consists of chitosan, sodium hyaluronate, and polyvinyl alcohol in a mass ratio of 1.5:0.5:1. The molecular weight of chitosan is 20,000, that of sodium hyaluronate is 1 million, and that of polyvinyl alcohol is 70,000. The surfactant is poloxamer 407, and the active ingredient is cassia seed extract.

[0081] The preparation method of the thermosensitive contact lens moisturizing gel is the same as in Example 1.

[0082] Comparative Example 1

[0083] The gel matrix in Example 1 was replaced with poloxamer 407 and poloxamer 188 in a mass ratio of 2:1, and everything else was the same as in Example 1.

[0084] Comparative Example 2

[0085] The mass ratio of chitosan, sodium hyaluronate, and polyvinyl alcohol in Example 1 was modified to 1.5:0.5:3, while other aspects remained the same as in Example 1.

[0086] Comparative Example 3

[0087] The mass ratio of chitosan, sodium hyaluronate, and polyvinyl alcohol in Example 1 was modified to 5:0.5:1, while other aspects remained the same as in Example 1.

[0088] Comparative Example 4

[0089] The polyvinyl alcohol in Example 1 is omitted, and everything else is the same as in Example 1.

[0090] Comparative Example 5

[0091] Sodium hyaluronate in Example 1 is omitted; otherwise, it is the same as in Example 1.

[0092] The thermosensitive contact lens lubricating gels prepared in Examples 1-6 and Comparative Examples 1-5 were placed in a water bath at 37°C, and the time required for them to change from a solution state to a gel state was recorded. The results are shown in Table 1.

[0093] Table 1 Phase transition time of thermosensitive contact lens lubricating gel

[0094]

[0095]

[0096] Fifty-five volunteers who had worn contact lenses for more than six months and experienced discomfort such as dryness and foreign body sensation during wear were randomly selected and divided into 11 groups. Each group received one drop of the eye-moisturizing gel from Examples 1-6 and Comparative Examples 1-5, twice daily. After one week, the effectiveness of the lenses was assessed, and the average score within each group was taken. The assessment results are shown in Table 2. The scoring criteria were: 1 point - poor, 2 points - poor, 3 points - average, 4 points - good, 5 points - good, 6 points - very good.

[0097] Table 2. Effectiveness rating of thermosensitive contact lens eye gel

[0098] Eye Gel score Eye Gel score Example 1 5.3 Comparative Example 1 3.5 Example 2 4.9 Comparative Example 2 3.2 Example 3 4.6 Comparative Example 3 4.2 Example 4 5.5 Comparative Example 4 2.9 Example 5 5.6 Comparative Example 5 2.8 Example 6 5.1 —— ——

[0099] As can be seen from Tables 1 and 2, the thermosensitive contact lens lubricating gels prepared in Examples 1 to 6 can achieve a gel phase transition within 40 seconds at 37°C, meeting the needs of eye use and providing a better experience for contact lens wearers; while the phase transition time of the thermosensitive contact lens lubricating gels prepared in Comparative Examples 1 to 5 is significantly prolonged, failing to meet the usage scenarios of lubricating gels and resulting in a poor user experience; Comparative Examples 4 and 5 are not suitable for the eyes because they cannot gel for a long time.

[0100] As can be seen from the above embodiments, the present invention provides a temperature-sensitive contact lens moisturizing gel that can achieve rapid gel formation and has long-lasting moisturizing and eye-protecting effects, providing a good user experience for contact lens wearers.

[0101] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A temperature-sensitive contact lens moisturizing gel, characterized in that, By mass fraction, it contains the following raw materials: The composition consists of 3-8% gel matrix, 0.3-3% surfactant, 0.2-1% osmotic pressure regulator, 2-6% active ingredient, 0.05-2% chelating agent, 0.03-1% buffer, and the balance being water for injection. The gel matrix contains chitosan, sodium hyaluronate, and polyvinyl alcohol.

2. The thermosensitive contact lens lubricating gel according to claim 1, characterized in that, The mass ratio of chitosan, sodium hyaluronate, and polyvinyl alcohol is 0.5–3:0.5–5:

1.

3. The thermosensitive contact lens lubricating gel according to claim 1 or 2, characterized in that, The active ingredients include active pharmaceutical ingredients and / or nutritional ingredients; The active pharmaceutical ingredient includes one or more of cyclosporine A, acyclovir, sodium hyaluronate, and carbomer; The nutrients include plant extracts.

4. The thermosensitive contact lens lubricating gel according to claim 3, characterized in that, The surfactant comprises one or more of polyvinylpyrrolidone, sodium dodecyl sulfonate, and poloxamer.

5. The thermosensitive contact lens lubricating gel according to claim 4, characterized in that, The osmotic pressure regulator contains one or more of sodium chloride, potassium chloride, and calcium chloride; The chelating agent comprises one or more of sodium alginate, sodium ethylenediaminetetraacetate, and sodium hexametaphosphate; The buffer contains one or more of borates, citrates, acetates, and carbonates.

6. The method for preparing the thermosensitive contact lens moisturizing gel according to any one of claims 1 to 5, characterized in that, It includes the following steps: 1) Mix chitosan, sodium hyaluronate, polyvinyl alcohol and water for injection in part 1, and stir to obtain a gel matrix solution; 2) Mix the surfactant, osmotic pressure regulator, active ingredient, chelating agent, buffer, and second-part injection water, and stir to obtain a mixture; 3) Add the mixture to the gel matrix solution and stir to obtain the thermosensitive contact lens moisturizing gel.

7. The preparation method according to claim 6, characterized in that, The mass ratio of the first part of the injected water to the second part of the injected water is 1:2 to 4.

8. The preparation method according to claim 6 or 7, characterized in that, Step 1) The stirring speed is 100-200 rpm, and the stirring time is 20-40 min.

9. The preparation method according to claim 8, characterized in that, Step 2) The stirring speed is 300-500 rpm, and the stirring time is 30-60 min.

10. The preparation method according to claim 9, characterized in that, Step 3) The stirring speed is 500-800 rpm, and the stirring time is 20-40 min.

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