Long-acting moisturizing contact lens eye lotion and preparation method thereof

Abstract

The invention belongs to the technical field of medical instruments, and provides a long-acting moisturizing contact lens eye lotion and a preparation method thereof. The contact lens eye moistening liquid provided by the invention is prepared from the following components in parts by mass: 0.01 to 0.5 part of gamma-polyglutamic acid, 0.5 to 1.2 parts of electrolyte component, 0.1 to 1.0 part of osmotic pressure regulator, 0.01 to 0.1 part of poloxamer 407 and 96 to 99.5 parts of buffer solution. According to the contact lens eye lotion disclosed by the invention, long-acting moisturizing, low irritation, high stability and excellent lens compatibility are realized through structural synergy of the polyglutamic acid and the electrolyte, functional synergy of the polyglutamic acid and the preservative and environmental synergy of the buffer solution and the osmotic pressure regulator, and the physiological function of natural tears is simulated.

Description

TECHNICAL FIELD

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

[0002] With the popularization of contact lenses, eye discomfort problems are increasingly prominent, about 70% of wearers have symptoms of dry eye, foreign body sensation, etc. due to decreased tear film stability. The physiological function of natural tears depends on the synergistic effect of its complex component system and structure, mainly including: the aqueous layer (98wt%) provides a moist environment, electrolytes (Na + , K + , Ca 2+ , etc.) maintain cell function, the mucin layer ensures tear film adhesion, and the lipid layer reduces evaporation.

[0003] The existing eye drop products have the following technical defects: (1) single component limitation: most products use sodium hyaluronate as the core moisturizing component, lack of multi-component synergistic design, the moisturizing duration is only 2-3h, and the ion balance environment of natural tears cannot be simulated; (2) irritation problem: traditional preservatives (such as benzalkonium chloride) can inhibit bacteria, but can damage the intercellular junction of corneal epithelial cells, leading to ocular surface sensitivity, especially for contact lens wearers, preservatives are easy to accumulate on the lens surface, and aggravate irritation; (3) insufficient stability: lack of synergistic stability mechanism among components, prone to delamination, abnormal viscosity due to pH fluctuation or ion strength change during storage, affecting the use effect; (4) poor lens compatibility: some high molecular weight moisturizing agents can interact with silicone hydrogel lenses, resulting in decreased lens oxygen permeability or precipitation.

[0004] Therefore, it is of great significance to study a contact lens eye drop with long-acting moisturizing, low irritation, high stability and excellent lens compatibility and a preparation method thereof. SUMMARY

[0005] The purpose of the present application is to provide a long-acting moisturizing contact lens eye drop and a preparation method thereof, which solves the problems of greater irritation, poor stability and poor lens compatibility of existing contact lens eye drops.

[0006] In order to achieve the above-mentioned purpose of the application, the present application provides the following technical scheme:

[0007] The present application provides a long-acting moisturizing contact lens eye drop, which comprises the following components in mass fraction:

[0008] 0.01-0.5 parts of gamma-polyglutamic acid, 0.5-1.2 parts of electrolyte component, 0.1-1.0 parts of osmotic pressure regulator, 0.01-0.1 parts of poloxamer 407 and 96-99.5 parts of buffer solution.

[0009] Preferably, the electrolyte component comprises sodium chloride, potassium chloride, calcium chloride and magnesium chloride, and the molar ratio of sodium chloride, potassium chloride, calcium chloride and magnesium chloride is 140:5-8:1-1.5:0.1-0.5.

[0010] Preferably, the osmotic pressure regulator is one or more of glycerol, propylene glycol and sorbitol.

[0011] Preferably, the buffer solution is a phosphate buffer solution, and the pH value of the phosphate buffer solution is 7-7.8.

[0012] Preferably, the molecular weight of the gamma-polyglutamic acid is 20-60 kDa.

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

[0014] The gamma-polyglutamic acid, the electrolyte component, the osmotic pressure regulator, the buffer solution and the poloxamer 407 are mixed and filtered to obtain the contact lens eye drop.

[0015] Preferably, the mixing time is 20-40 min, and the mixing temperature is 25-45 DEG C.

[0016] Preferably, the pore size of the filter is 0.2-0.25 mu m.

[0017] Via the technical solution, compared with the prior art, the application has the following beneficial effects:

[0018] The contact lens eye drop realizes long-acting moisturizing, low irritation, high stability and excellent lens compatibility by the structural synergy of the polyglutamic acid and the electrolyte, the functional synergy of the preservative, the environmental synergy of the buffer solution and the osmotic pressure regulator, and simulates the physiological function of natural tear.

[0019] The contact lens eye drop obtained by the application has the following characteristics:

[0020] (1) long-acting moisturizing: the reticular crosslinking structure of the polyglutamic acid and the electrolyte realizes moisturizing for 6-8 h;

[0021] (2) high stability: the synergy of the buffer solution and the osmotic pressure regulator makes the product not stratified and the viscosity change rate less than 10% when stored for 3 months at 5-40 DEG C;

[0022] (3) excellent lens compatibility: the electrically neutral design of the composite film reduces lens precipitation, has little influence on oxygen permeability, and is suitable for various materials such as silicone hydrogel and hydrogel;

[0023] (4) Biomimetic adaptability: It simulates the ion ratio and pH environment of natural tears, and increases the tear film breakup time (BUT) from less than 5s before use to more than 5s, significantly improving eye comfort. Detailed Implementation

[0024] This invention provides a long-lasting moisturizing contact lens eye drops, the contact lens eye drops comprising the following components in parts by weight:

[0025] 0.01–0.5 parts of γ-polyglutamic acid, 0.5–1.2 parts of electrolyte components, 0.1–1.0 parts of osmotic pressure regulator, 0.01–0.1 parts of poloxamer 407, and 96–99.5 parts of buffer solution.

[0026] In this invention, the mass fraction of the γ-polyglutamic acid is preferably 0.1 to 0.4 parts, more preferably 0.15 to 0.35 parts, and even more preferably 0.2 to 0.3 parts; the mass fraction of the electrolyte component is preferably 0.6 to 1.1 parts, more preferably 0.7 to 1 part, and even more preferably 0.8 to 0.9 parts; the mass fraction of the osmotic pressure regulator is preferably 0.2 to 0.9 parts, more preferably 0.4 to 0.8 parts, and even more preferably 0.5 to 0.6 parts; the mass fraction of the poloxamer 407 is preferably 0.02 to 0.08 parts, more preferably 0.03 to 0.07 parts, and even more preferably 0.05 to 0.06 parts; and the mass fraction of the buffer solution is preferably 96.5 to 99 parts, more preferably 97 to 98.5 parts, and even more preferably 97.5 to 98 parts.

[0027] In this invention, the electrolyte components preferably include sodium chloride, potassium chloride, calcium chloride, and magnesium chloride. The molar ratio of sodium chloride, potassium chloride, calcium chloride, and magnesium chloride is preferably 140:5-8:1-1.5:0.1-0.5, more preferably 140:5.5-7:1.1-1.4:0.2-0.4, and even more preferably 140:6-6.5:1.2-1.3:0.3-0.35.

[0028] In this invention, the osmotic pressure regulator is preferably one or more of glycerol, propylene glycol, and sorbitol.

[0029] In this invention, the buffer solution is preferably a phosphate buffer solution, and the pH value of the phosphate buffer solution is preferably 7 to 7.8, more preferably 7.2 to 7.7, and even more preferably 7.4 to 7.5.

[0030] In this invention, the molecular weight of the γ-polyglutamic acid is preferably 20-60 kDa, more preferably 30-50 kDa, and even more preferably 40-45 kDa.

[0031] In this invention, the amount of osmotic pressure regulator added is such that it can synergistically regulate osmotic pressure with the electrolyte. The regulated osmotic pressure is preferably 280–320 mOsm / L, more preferably 290–310 mOsm / L, and even more preferably 300–305 mOsm / L.

[0032] In this invention, the carboxyl group (-COOH) on the polyglutamic acid molecular chain dissociates into a negatively charged group at a pH of 7–7.8, reacting with Ca in the electrolyte. 2+ and Mg 2+ (Divalent cations) form a network cross-linked structure through charge bridging, which significantly improves the mechanical strength and water-locking capacity of the hydration membrane.

[0033] In this invention, the hydrophilic polyoxyethylene segments of poloxamer 407 form hydrogen bonds with the hydroxyl groups of polyglutamic acid, constructing a lubricating outer layer on the surface of the hydrated film and reducing the coefficient of friction. At the same time, the micelles formed by the self-assembly of its hydrophobic polyoxypropylene segments are anchored by the polyglutamic acid network structure and released slowly, which greatly prolongs the antibacterial duration of the contact lens eye drops, and reduces the minimum inhibitory concentration and irritation.

[0034] This invention also provides a method for preparing a long-lasting moisturizing contact lens eye drop, comprising the following steps:

[0035] The contact lens lubricant was obtained by mixing γ-polyglutamic acid, electrolyte components, osmotic pressure regulator, buffer solution and poloxamer 407 and then filtering.

[0036] In this invention, the mixing time is preferably 20-40 min, more preferably 25-35 min, and even more preferably 30-32 min; the mixing temperature is preferably 25-45°C, more preferably 30-40°C, and even more preferably 34-36°C.

[0037] In this invention, the mixing is preferably carried out by adding electrolyte components and osmotic pressure regulator to the buffer solution and stirring once, then adding polyglutamic acid and stirring a second time, and finally adding poloxamer 407 and mixing well to complete the mixing.

[0038] The stirring time for one stirring session is preferably 4 to 7 minutes, more preferably 5 to 6 minutes; the stirring temperature for one stirring session is preferably 25 to 32°C, more preferably 26 to 30°C, and even more preferably 27 to 28°C; and the stirring speed for one stirring session is preferably 280 to 320 rpm, more preferably 290 to 310 rpm, and even more preferably 300 rpm.

[0039] The preferred time for the secondary stirring is 28-34 min, more preferably 29-33 min, and even more preferably 30-32 min. The preferred temperature for the secondary stirring is 38-43℃, more preferably 39-42℃, and even more preferably 40-41℃. The preferred speed for the secondary stirring is 120-160 rpm, more preferably 130-150 rpm, and even more preferably 140 rpm.

[0040] In this invention, the pore size of the filter is preferably 0.2-0.25 μm, more preferably 0.21-0.24 μm, and even more preferably 0.22-0.23 μm.

[0041] 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.

[0042] In this invention, the parts in the examples and comparative examples are all parts by mass.

[0043] Example 1

[0044] In this embodiment, the components and their contents are as follows: 0.25 parts γ-polyglutamic acid (molecular weight of 50 kDa), 0.75 parts electrolyte components (sodium chloride, potassium chloride, calcium chloride and magnesium chloride in a molar ratio of 140:6:1.2:0.3), 0.55 parts glycerol, 0.05 parts poloxamer 407 and 98.4 parts phosphate buffer (pH value of 7.4);

[0045] Preparation method:

[0046] After adding electrolyte components and glycerol to phosphate buffer, stir at 300 rpm at 30°C for 6 min. Then add γ-polyglutamic acid and stir at 140 rpm at 40°C for 30 min until the γ-polyglutamic acid is completely hydrated and the solution is clear and transparent. After cooling to 25°C, add poloxamer 407, stir well, and then filter aseptically through a 0.22 μm microporous membrane to obtain contact lens lubricating solution.

[0047] Example 2

[0048] In this embodiment, the components and their contents are as follows: 0.1 parts γ-polyglutamic acid (molecular weight 40kDa), 0.85 parts electrolyte components (sodium chloride, potassium chloride, calcium chloride and magnesium chloride in a molar ratio of 140:6.5:1.3:0.35), 0.4 parts propylene glycol, 0.03 parts poloxamer 407 and 98.62 parts phosphate buffer (pH 7.5);

[0049] The other steps are the same as in Example 1.

[0050] Example 3

[0051] In this embodiment, the components and their contents are as follows: 0.4 parts γ-polyglutamic acid (molecular weight of 40 kDa), 1 part electrolyte component (sodium chloride, potassium chloride, calcium chloride and magnesium chloride in a molar ratio of 140:6.5:1.3:0.35), 0.8 parts propylene glycol, 0.08 parts poloxamer 407 and 97.72 parts phosphate buffer (pH value of 7.5);

[0052] The other steps are the same as in Example 1.

[0053] Comparative Example 1

[0054] Replace "poloxamer 407" with "benzalkonium chloride" in Example 1, and follow the same steps as in Example 1.

[0055] Comparative Example 2

[0056] Replace “γ-polyglutamic acid” in Example 1 with the same mass fraction of phosphate buffer, and follow the same steps as in Example 1.

[0057] Comparative Example 3

[0058] Replace “0.55 parts glycerol” in Example 1 with “1.2 parts glycerol”, and follow the same steps as in Example 1.

[0059] The following performance tests were conducted on the contact lens lubricants obtained in Examples 1-3 and Comparative Examples 1-3.

[0060] Moisture retention test: 0.5g of sample was accurately weighed and spread evenly in a specific petri dish in a constant temperature and humidity chamber at 20℃ and 45% RH, and the initial weight W0 was recorded. The sample was then weighed every 1 hour thereafter (W0). t ), calculate the water evaporation rate: Evaporation rate (%) = [(W0 - W t [(W0)×100%] Record the time (T) required for the water evaporation rate to reach 50%. 50 ), T 50 The longer the duration, the better the moisturizing effect. The test results are shown in Table 1.

[0061] Lubricity test: An in vitro coefficient of friction (COF) meter was used. A standard silicone hydrogel contact lens material was used as the upper sample, and a fresh, excised porcine cornea was used as the lower sample. Under a PBS lubricating environment at 37°C, a fixed positive pressure was applied, and reciprocating friction was performed. The instrument automatically calculated and recorded the dynamic coefficient of friction (COF). A lower COF indicates better lubrication performance. The test results are shown in Table 1.

[0062] Stability test: The samples were placed in a constant temperature and humidity chamber at 40℃ and 75% relative humidity for 3 months. Samples were taken at the end of October and March, and the viscosity change rate was measured at 25℃ using a rotational viscometer: viscosity change rate (%) = [(η3-η0) / η0] × 100%.

[0063] Lens compatibility: Silicone hydrogel lenses from the same batch were immersed in the sample solution and PBS (control) for 72 hours respectively. After rinsing with PBS, the oxygen permeability of the lenses was measured using a lens oxygen permeability (Dk) meter. The rate of change in oxygen permeability was calculated as follows: Rate of change (%) = [(Dk)] 样品 [-Dk control) / Dk control]×100%. The smaller the rate of change, the less impact it has on the oxygen permeability of the lens, and the better the compatibility.

[0064] Table 1. Performance test results of contact lens eye drops obtained in Examples 1-3 and Comparative Examples 1-3

[0065]

[0066] As shown in Table 1, the contact lens lubricating solutions obtained in Examples 1-3 are comprehensively superior to those in Comparative Examples 1-3 in terms of durability, lubricity, stability, and oxygen permeability. The moisturizing durability of the lubricating solutions obtained in Examples 1-3 is nearly twice that of Comparative Examples 1-3; the coefficient of friction of Examples 1 and 3 is as low as 0.097-0.098, significantly improving wearing comfort, while the coefficient of friction of the comparative examples is as high as 1.132-1.141; in addition, the viscosity change rate and the negative impact on lens oxygen permeability of the examples are much lower than those of Comparative Examples 1-3, which comprehensively demonstrates that the formulations of the examples have outstanding advantages in prolonging the action time, maintaining stability, and reducing interference with lens performance.

[0067] 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 long-lasting moisturizing contact lens solution, characterized in that, The contact lens lubricant comprises the following components in parts by weight: 0.01–0.5 parts of γ-polyglutamic acid, 0.5–1.2 parts of electrolyte components, 0.1–1.0 parts of osmotic pressure regulator, 0.01–0.1 parts of poloxamer 407, and 96–99.5 parts of buffer solution.

2. The long-lasting moisturizing contact lens eye drop according to claim 1, characterized in that, The electrolyte components include sodium chloride, potassium chloride, calcium chloride and magnesium chloride, with a molar ratio of 140:5~8:1~1.5:0.1~0.

5.

3. The long-lasting moisturizing contact lens eye drop according to claim 2, characterized in that, The osmotic pressure regulator is one or more of glycerol, propylene glycol, and sorbitol.

4. The long-lasting moisturizing contact lens eye drop according to claim 2 or 3, characterized in that, The buffer solution is a phosphate buffer solution with a pH of 7 to 7.

8.

5. The long-lasting moisturizing contact lens eye drop according to claim 4, characterized in that, The molecular weight of the γ-polyglutamic acid is 20–60 kDa.

6. A method for preparing a long-lasting moisturizing contact lens eye drop according to any one of claims 1 to 5, characterized in that, Includes the following steps: The contact lens lubricant was obtained by mixing γ-polyglutamic acid, electrolyte components, osmotic pressure regulator, buffer solution and poloxamer 407 and then filtering.

7. The method for preparing a long-lasting moisturizing contact lens eye drop according to claim 6, characterized in that, The mixing time is 20–40 min, and the mixing temperature is 25–45 °C.

8. The method for preparing a long-lasting moisturizing contact lens eye drop according to claim 6, characterized in that, The pore size of the filter is 0.2 to 0.25 μm.

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