Contact lens eye-moistening liquid based on lipidosome and preparation method of contact lens eye-moistening liquid

Abstract

The invention provides a lipidosome-based contact lens eye lotion and a preparation method thereof, and belongs to the technical field of contact lens care. The contact lens eye moistening liquid provided by the invention is prepared from the following raw materials in parts by weight: 0.5 to 2 parts of hyaluronic acid, 0.005 to 0.1 part of hydroxypropyl methyl cellulose, 0.1 to 1 part of double vitamin liposome, 0.01 to 0.5 part of ethylenediamine tetraacetic acid, 0.5 to 2 parts of osmotic pressure regulator, 0.1 to 2 parts of pH regulator and 95 to 99 parts of water. According to the invention, fat-soluble VE and water-soluble VB12 are compositely embedded through a liposome slow release technology, and a synergistic moisturizing network of multi-molecular-weight sodium hyaluronate and hydroxypropyl methylcellulose is combined, so that nanocrystallization and stable dispersion of fat-soluble components are realized.

Description

Technical Field

[0001] This invention relates to the field of contact lens care technology, and in particular to a liposome-based contact lens lubricant and its preparation method. Background Technology

[0002] With the rising global myopia rate and increasing demand for cosmetic lenses, the user base for contact lenses is constantly expanding. However, eye health problems caused by long-term contact lens wear are also becoming increasingly serious, including dry eye syndrome and oxidative stress damage. Contact lenses trap moisture in the tear film, disrupting the natural dynamics of tear fluid, leading to dry and burning eyes. Traditional eye drops only provide 2-4 hours of hydration, which is far from sufficient for 16 hours of wear. Furthermore, lenses absorb lipids from the tear film and are exposed to ultraviolet light, which can induce lipid peroxidation, leading to elevated malondialdehyde levels and reactive oxygen species attacking the corneal epithelium, causing punctate corneal erosions.

[0003] For example, Chinese invention patent application CN115461652A discloses a technique for embedding vitamin E into a silicone hydrogel lens matrix, achieving a sustained-release effect through physical encapsulation. However, the active ingredient in this technique cannot be released to the ocular surface, and vitamin E cannot be released from the contact lens, which may actually worsen dry eye symptoms. Another example is Chinese invention patent application CN118480411A, which discloses a technique for encapsulating water-soluble vitamin B12 with liposomes and combining it with hyaluronic acid for moisturizing. However, this technique cannot deliver fat-soluble active ingredients, being limited to encapsulating water-soluble vitamin B12, and fails to solve the problems of nano-sizing and stable dispersion of fat-soluble components such as vitamin E; furthermore, the release rate of vitamin B12 liposomes in the composite moisturizing layer is too fast, failing to provide a long-lasting moisturizing effect.

[0004] Therefore, it is particularly important to provide a contact lens eye drop that has a long-lasting moisturizing effect and can achieve nano-sized and stable dispersion of fat-soluble ingredients. Summary of the Invention

[0005] The purpose of this invention is to provide a liposome-based contact lens lubricant and its preparation method, in order to solve the technical problems of excessively fast release rate, short wetting time, and inability to achieve nano-sized and stable dispersion of lipid-soluble components in the prior art.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a liposome-based contact lens lubricant, comprising the following raw materials in parts by weight: Hyaluronic acid 0.5-2 parts, Hydroxypropyl methylcellulose 0.005~0.1 parts, Divitamin liposomes 0.1-1 part, 0.01~0.5 parts of ethylenediaminetetraacetic acid (EDTA). Osmotic pressure regulator 0.5~2 parts, pH adjuster 0.1~2 parts, 95-99 parts water.

[0007] Furthermore, the hyaluronic acid is a mixture of hyaluronic acid with three molecular weights: low molecular weight, medium molecular weight, and high molecular weight. The molecular weights of the low molecular weight, medium molecular weight, and high molecular weight hyaluronic acid are 50,000 to 200,000 Da, 200,000 to 1,000,000 Da, and 1,000,000 to 4,000,000 Da, respectively. The mass ratio of the low molecular weight, medium molecular weight, and high molecular weight hyaluronic acid is 0.1~0.3:0.2~0.4:0.4~0.6.

[0008] Furthermore, the dual vitamin liposomes are vitamin E and vitamin B12, and the mass ratio of vitamin E to vitamin B12 is 1:2~5.

[0009] Furthermore, the osmotic pressure regulator includes sodium chloride and / or potassium chloride.

[0010] Furthermore, the pH adjuster includes boric acid and / or disodium phosphate.

[0011] This invention also provides a method for preparing a liposome-based contact lens lubricant, comprising the following steps: 1) Dissolve phospholipids, cholesterol and vitamin E in chloroform, then remove chloroform by rotary evaporation under nitrogen protection to obtain an oil phase; dissolve vitamin B12 in water to obtain an aqueous phase; add the aqueous phase to the oil phase for homogenization to obtain a liposome suspension, and finally add aldehyde-modified chitosan to mix to obtain a dual vitamin liposome. 2) Dissolve high molecular weight hyaluronic acid in water, then cool it for the first time before adding medium molecular weight hyaluronic acid and mixing. Then cool it for the second time before adding low molecular weight hyaluronic acid and hydroxypropyl methylcellulose and mixing to obtain a transparent colloid. 3) Add ethylenediaminetetraacetic acid and bisvitamin liposomes to the transparent colloid and mix. Finally, add the osmotic pressure regulator and pH regulator.

[0012] Furthermore, in step 1), the ratio of phospholipids, cholesterol, vitamin E, and chloroform is 1g:0.2~0.3g:0.04~0.2g:3~5mL; The mass ratio of VB12 to water is 1:12~20; The mass ratio of VE to aldehyde-modified chitosan is 0.04~0.2:0.05~0.1.

[0013] Furthermore, in step 1), the dissolution temperature is 30~50℃; The VB12 dissolves in water at a temperature of 50~70℃; The pressure of the homogenizer is 700~900 bar; The mixing is carried out by stirring at a temperature of 30-50°C for 1-3 hours. The particle size of the dual-vitamin liposomes is 100~200nm.

[0014] Furthermore, in step 2), the dissolution temperature is 70~90℃, the first cooling temperature is 40~60℃, and the second cooling temperature is 20~40℃; The mixing time is 20-40 minutes.

[0015] Furthermore, in step 3), the mixing temperature is 15~35℃, the mixing is carried out by stirring, and the stirring speed is 80~120rpm.

[0016] The beneficial effects of this invention are: This invention reduces water molecule permeation by utilizing the hydrophobic barrier of vitamin E, thereby indirectly reducing the diffusion rate of vitamin B12; the internal aqueous phase of vitamin B12 maintains the osmotic pressure stability of liposomes, preventing sudden release of vitamin E, and achieving a sustained-release effect through the synergistic effect of vitamin E and vitamin B12. This invention constructs a multi-level HA / HPMC network to achieve a triple moisturizing mechanism of "rapid penetration - gap filling - long-lasting water retention". By using liposome sustained-release technology to encapsulate lipid-soluble vitamin E and water-soluble vitamin B12, combined with the synergistic moisturizing network of high molecular weight sodium hyaluronate (HA) and hydroxypropyl methylcellulose (HPMC), it solves the problems of nano-sized and stable dispersion of lipid-soluble components such as vitamin E, as well as the technical problem of excessively rapid release rate of vitamin B12 liposomes in the composite moisturizing layer, thus achieving dual protection against dry eyes and oxidative stress. Detailed Implementation

[0017] This invention provides a liposome-based contact lens lubricant, comprising the following raw materials in parts by weight: Hyaluronic acid 0.5-2 parts, Hydroxypropyl methylcellulose 0.005~0.1 parts, Divitamin liposomes 0.1-1 part, 0.01~0.5 parts of ethylenediaminetetraacetic acid (EDTA). Osmotic pressure regulator 0.5~2 parts, pH adjuster 0.1~2 parts, 95-99 parts water.

[0018] In this invention, the content of hyaluronic acid is preferably 0.6 to 1.9 parts by mass, and more preferably 0.7 to 1.8 parts by mass.

[0019] In this invention, the hyaluronic acid is a mixture of hyaluronic acid with three molecular weights: low molecular weight, medium molecular weight, and high molecular weight. The molecular weights of the low molecular weight, medium molecular weight, and high molecular weight hyaluronic acid are 50,000 to 200,000 Da, 200,000 to 1,000,000 Da, and 1,000,000 to 4,000,000 Da, respectively. The mass ratio of the low molecular weight, medium molecular weight, and high molecular weight hyaluronic acid is 0.1~0.3:0.2~0.4:0.4~0.6, preferably 0.15~0.25:0.25~0.35:0.45~0.55, and more preferably 0.2:0.3:0.5.

[0020] In this invention, the role of low molecular weight hyaluronic acid is to quickly penetrate into the micropores on the lens surface; the role of medium molecular weight hyaluronic acid is to fill the gaps in the HA network; and the role of high molecular weight hyaluronic acid is to form an outer physical barrier to reduce moisture evaporation.

[0021] In this invention, the content of hydroxypropyl methylcellulose is preferably 0.008 to 0.09 parts by weight, and more preferably 0.01 to 0.08 parts by weight.

[0022] In this invention, the role of hydroxypropyl methylcellulose is to reduce the coefficient of friction between the lens and the cornea, enhance lubrication, and improve wearing comfort.

[0023] In this invention, the content of the dual vitamin liposomes is preferably 0.2 to 0.9 parts by weight, and more preferably 0.3 to 0.8 parts by weight.

[0024] In this invention, the dual vitamin liposomes are vitamin E and vitamin B12, and the mass ratio of vitamin E to vitamin B12 is 1:2~5, preferably 1:2.5~4.5, and more preferably 1:3~4.

[0025] In this invention, the role of VE is to inhibit tear film lipid peroxidation; the role of VB12 is to promote corneal epithelial repair.

[0026] In this invention, the content of ethylenediaminetetraacetic acid is preferably 0.05 to 0.45 parts by mass, and more preferably 0.1 to 0.4 parts by mass.

[0027] In this invention, the content of the osmotic pressure regulator is preferably 0.6 to 1.8 parts by weight, and more preferably 0.7 to 1.5 parts by weight.

[0028] In this invention, the osmotic pressure regulator includes sodium chloride and / or potassium chloride, preferably sodium chloride.

[0029] In this invention, the content of the pH adjuster is preferably 0.15 to 1.8 parts by mass, and more preferably 0.2 to 1.5 parts by mass.

[0030] In this invention, the pH adjuster includes boric acid and / or disodium phosphate, preferably boric acid.

[0031] In this invention, the water content is preferably 95.5 to 98.5 parts by mass, and more preferably 96 to 98 parts by mass.

[0032] This invention also provides a method for preparing a liposome-based contact lens lubricant, comprising the following steps: 1) Dissolve phospholipids, cholesterol and vitamin E in chloroform, then remove chloroform by rotary evaporation under nitrogen protection to obtain an oil phase; dissolve vitamin B12 in water to obtain an aqueous phase; add the aqueous phase to the oil phase for homogenization to obtain a liposome suspension, and finally add aldehyde-modified chitosan to mix to obtain a dual vitamin liposome. 2) Dissolve high molecular weight hyaluronic acid in water, then cool it for the first time before adding medium molecular weight hyaluronic acid and mixing. Then cool it for the second time before adding low molecular weight hyaluronic acid and hydroxypropyl methylcellulose and mixing to obtain a transparent colloid. 3) Add ethylenediaminetetraacetic acid and bisvitamin liposomes to the transparent colloid and mix. Finally, add the osmotic pressure regulator and pH regulator.

[0033] In this invention, in step 1), the ratio of phospholipids, cholesterol, vitamin E, and chloroform is 1g:0.2~0.3g:0.04~0.2g:3~5mL, preferably 1g:0.22~0.28g:0.06~0.18g:3.5~4.5mL, and more preferably 1g:0.25g:0.1~0.15g:4mL; The mass ratio of VB12 to water is 1:12~20, preferably 1:13~19, and more preferably 1:14~18; The mass ratio of VE to aldehyde-modified chitosan is 0.04~0.2:0.05~0.1, preferably 0.06~0.1:0.06~0.09, and more preferably 0.1~0.15:0.07~0.085.

[0034] In this invention, in step 1), the dissolution temperature is 30~50℃, preferably 35~45℃, and more preferably 40℃; The temperature at which VB12 dissolves in water is 50~70℃, preferably 55~65℃, and more preferably 60℃; The pressure of the homogenizer is 700~900 bar, preferably 750~850 bar, and more preferably 800 bar; The mixing is carried out by stirring, and the stirring temperature is 30~50℃, preferably 35~45℃, more preferably 40℃; the stirring time is 1~3h, preferably 1.5~2.5h, more preferably 2h; The particle size of the dual-vitamin liposomes is 100-200 nm, preferably 120-180 nm, and more preferably 140-160 nm.

[0035] In this invention, in step 2), the dissolution temperature is 70~90℃, preferably 75~85℃, and more preferably 80℃; the first cooling temperature is 40~60℃, preferably 45~55℃, and more preferably 50℃; the second cooling temperature is 20~40℃, preferably 25~35℃, and more preferably 30℃. The mixing time is independently 20-40 min, preferably 25-35 min, and more preferably 30 min.

[0036] In this invention, in step 3), the mixing temperature is 15~35℃, preferably 20~30℃, and more preferably 25℃; the mixing is carried out by stirring, and the stirring speed is 80~120rpm, preferably 85~115rpm, and more preferably 90~110rpm.

[0037] 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.

[0038] Example 1

[0039] 1g of phospholipids, 0.25g of cholesterol, and 0.1g of vitamin E were dissolved in 4mL of chloroform at 40℃. The chloroform was then removed by rotary evaporation under nitrogen protection to obtain the oil phase. 0.3g of vitamin B12 was dissolved in 4.5g of water at 60℃ to obtain the aqueous phase. The aqueous phase was added to the oil phase and homogenized at 800 bar to obtain a liposome suspension. Finally, 0.0825g of aldehyde-modified chitosan was added and mixed to obtain bivitamin liposomes with a particle size of 150nm. Dissolve 0.5 parts of high molecular weight hyaluronic acid with a molecular weight of 2 million Da in 97 parts of water at 80°C, then cool to 50°C and add 0.3 parts of medium molecular weight hyaluronic acid with a molecular weight of 500,000 Da. After cooling to 30°C again, add 0.2 parts of low molecular weight hyaluronic acid with a molecular weight of 100,000 Da and 0.05 parts of hydroxypropyl methylcellulose to obtain a transparent colloid. Add 0.02 parts of ethylenediaminetetraacetic acid and 0.5 parts of dual vitamin liposomes to a transparent colloid and mix at 100 rpm and 30°C. After mixing evenly, add 1 part of sodium chloride and 0.5 parts of boric acid and mix well to obtain contact lens lubricant.

[0040] Example 2

[0041] Compared with Example 1, the difference in Example 2 is that 0.8 parts of hyaluronic acid, 0.08 parts of hydroxypropyl methylcellulose, 0.2 parts of bisvitamin liposomes, 0.03 parts of ethylenediaminetetraacetic acid, 1 part of sodium chloride, 0.5 parts of boric acid, and 98 parts of water are used.

[0042] Example 3

[0043] Compared with Example 1, the difference is that in Example 3, there are 1.7 parts of hyaluronic acid, 0.03 parts of hydroxypropyl methylcellulose, 0.7 parts of bisvitamin liposomes, 0.01 parts of ethylenediaminetetraacetic acid, 1 part of sodium chloride, 0.5 parts of boric acid, and 96 parts of water.

[0044] Comparative Example 1

[0045] The difference between this example and Example 1 is that the molecular weight of hyaluronic acid in Comparative Example 1 is 1.5 million Da.

[0046] Comparative Example 2

[0047] The difference between Comparative Example 2 and Example 1 is that VB12 was not added.

[0048] Comparative Example 3

[0049] The difference between this example and Example 1 is that Comparative Example 3 did not include Vitamin E.

[0050] Comparative Example 4

[0051] The difference between this example and Example 1 is that hydroxypropyl methylcellulose was not added in Comparative Example 4.

[0052] Comparative Example 5

[0053] Compared with Example 1, the difference lies in the following in Comparative Example 5: 2.5 parts hyaluronic acid, 0.05 parts hydroxypropyl methylcellulose, 0.05 parts bisvitamin liposomes, 0.1 parts ethylenediaminetetraacetic acid, 0.5 parts sodium chloride, 0.3 parts boric acid, and 97.5 parts water.

[0054] The performance of the contact lens lubricating solutions prepared in Examples 1-3 and Comparative Examples 1-5 was tested, and the test results are shown in Table 1.

[0055] Table 1. Performance test results of contact lens eye drops prepared in Examples 1-3 and Comparative Examples 1-5

[0056] As can be seen from the above embodiments, the present invention provides a liposome-based contact lens lubricating solution and its preparation method. The contact lens lubricating solution comprises the following raw materials in parts by weight: 0.5-2 parts hyaluronic acid, 0.005-0.1 parts hydroxypropyl methylcellulose, 0.1-1 parts dual-vitamin liposomes, 0.01-0.5 parts ethylenediaminetetraacetic acid, 0.5-2 parts osmotic pressure regulator, 0.1-2 parts pH regulator, and 95-99 parts water. The present invention uses liposome sustained-release technology to encapsulate lipid-soluble vitamin E and water-soluble vitamin B12, combined with a synergistic moisturizing network of high molecular weight sodium hyaluronate and hydroxypropyl methylcellulose. As shown in Table 1, the contact lens lubricating solution prepared by the present invention has a long moisturizing effect and achieves nano-sized and stable dispersion of lipid-soluble components.

[0057] 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 liposome-based contact lens lubricant, characterized in that, Including the following parts by weight of raw materials: Hyaluronic acid 0.5-2 parts, Hydroxypropyl methylcellulose 0.005~0.1 parts, Divitamin liposomes 0.1-1 part, 0.01~0.5 parts of ethylenediaminetetraacetic acid (EDTA). Osmotic pressure regulator 0.5~2 parts, pH adjuster 0.1~2 parts, 95-99 parts water.

2. The liposome-based contact lens lubricant according to claim 1, characterized in that, The hyaluronic acid is a mixture of low molecular weight, medium molecular weight and high molecular weight hyaluronic acid, with molecular weights of 50,000~200,000 Da, 200,000~1,000,000 Da and 1,000,000~4,000,000 Da, respectively. The mass ratio of the low molecular weight, medium molecular weight, and high molecular weight hyaluronic acid is 0.1~0.3:0.2~0.4:0.4~0.

6.

3. The liposome-based contact lens lubricant according to claim 1 or 2, characterized in that, The dual vitamin liposomes are vitamin E and vitamin B12, and the mass ratio of vitamin E to vitamin B12 is 1:2~5.

4. The liposome-based contact lens lubricant according to claim 3, characterized in that, The osmotic pressure regulator includes sodium chloride and / or potassium chloride.

5. The liposome-based contact lens lubricant according to claim 4, characterized in that, The pH adjuster includes boric acid and / or disodium phosphate.

6. A method for preparing a liposome-based contact lens lubricating solution according to any one of claims 1 to 5, characterized in that, Includes the following steps: 1) Dissolve phospholipids, cholesterol and vitamin E in chloroform, then remove chloroform by rotary evaporation under nitrogen protection to obtain an oil phase; dissolve vitamin B12 in water to obtain an aqueous phase; add the aqueous phase to the oil phase for homogenization to obtain a liposome suspension, and finally add aldehyde-modified chitosan to mix to obtain a dual vitamin liposome. 2) Dissolve high molecular weight hyaluronic acid in water, then cool it for the first time before adding medium molecular weight hyaluronic acid and mixing. Then cool it for the second time before adding low molecular weight hyaluronic acid and hydroxypropyl methylcellulose and mixing to obtain a transparent colloid. 3) Add ethylenediaminetetraacetic acid and bisvitamin liposomes to the transparent colloid and mix. Finally, add the osmotic pressure regulator and pH regulator.

7. The method for preparing liposome-based contact lens lubricating solution according to claim 6, characterized in that, In step 1), the ratio of phospholipids, cholesterol, vitamin E, and chloroform is 1g: 0.2~0.3g: 0.04~0.2g: 3~5mL; The mass ratio of VB12 to water is 1:12~20; The mass ratio of VE to aldehyde-modified chitosan is 0.04~0.2:0.05~0.

1.

8. The method for preparing liposome-based contact lens lubricating solution according to claim 7, characterized in that, In step 1), the dissolution temperature is 30~50℃; The VB12 dissolves in water at a temperature of 50~70℃; The pressure of the homogenizer is 700~900 bar; The mixing is carried out by stirring at a temperature of 30-50°C for 1-3 hours. The particle size of the dual-vitamin liposomes is 100~200nm.

9. The method for preparing liposome-based contact lens lubricating solution according to claim 7 or 8, characterized in that, In step 2), the dissolution temperature is 70~90℃, the first cooling temperature is 40~60℃, and the second cooling temperature is 20~40℃; The mixing time is 20-40 minutes.

10. The method for preparing liposome-based contact lens lubricating solution according to claim 9, characterized in that, In step 3), the mixing temperature is 15~35℃, the mixing is carried out by stirring, and the stirring speed is 80~120rpm.

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