Eye protection patch based on solid nitric oxide slow release and low-temperature curing preparation process thereof

Abstract

The invention relates to the technical field of eyes, in particular to an eye protection patch based on solid nitric oxide slow release and a low-temperature curing preparation process thereof.The eye protection patch comprises an environment-friendly non-woven fabric carrier and active ingredients loaded on the environment-friendly non-woven fabric carrier, 0.5-2% of a ginger extract; 3-8% of menthol; 0.01%-0.1% of a cordyceps sinensis extract; 0.05 to 0.2 percent of soil mineral substances; 0.05 to 0.3 percent of lavender oil; 0.01 to 0.1 percent of solid nitric oxide; the method further comprises steps. S100, the gaseous NO is introduced into a condensation cavity with the temperature of-40 DEG C to be cured, and solid NO is formed; s200, mixing solid NO with mineral oil and a plant extract to form slurry; s300, a non-woven fabric is coated with the slurry; and S400, performing vacuum freeze drying and shaping. The preparation method has the effects of long-acting slow release, targeted synergism and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of eyes, in particular, to an eye-care patch based on solid nitric oxide release and a low-temperature solidification preparation process thereof. BACKGROUND

[0002] Long-term eye overuse can easily lead to blood circulation disorder of the eye, causing visual fatigue, vision loss and other problems. In the prior art, eye patches are mostly used for short-term relief through hot compress, cold compress or plant extracts (such as menthol), but lack of targeted regulation of blood circulation. Nitric oxide (NO) has the function of dilating blood vessels and improving microcirculation, but its gaseous form is difficult to store stably, and the prior art mostly uses NO donor compounds (such as nitroglycerin), which has the problems of uncontrollable release and low bioavailability. SUMMARY

[0003] To solve the above problems, the purpose of the present application is to provide an eye-care patch based on solid nitric oxide release and a low-temperature solidification preparation process thereof.

[0004] The present application provides the following technical solutions: an eye-care patch based on solid nitric oxide release and a low-temperature solidification preparation process thereof, which is composed of the following components in mass percentage:

[0005] An environmentally friendly non-woven fabric carrier and active ingredients loaded thereon:

[0006] Mineral oil 30-40%; ginger extract 0.5-2%; menthol 3-8%; cordyceps sinensis extract 0.01-0.1%; soil minerals 0.05-0.2%; lavender oil 0.05-0.3%; solid nitric oxide 0.01-0.1%.

[0007] Preferably, the solid nitric oxide is prepared by a low-temperature solidification process:

[0008] Condense gaseous NO into solid particles with a particle size of 1-10 μm at an environment of-50℃ to-30℃;

[0009] Mix the solid NO particles with the remaining ingredients and coat them on the non-woven fabric;

[0010] Vacuum freeze-dry and shape for 2 hours at a temperature of-45℃ and a pressure of 10 Pa.

[0011] Preferably, the condensation temperature is-40℃±2℃.

[0012] Preferably, the mass percentage of the active ingredients is:

[0013] Mineral oil 35%; ginger extract 1%; menthol 5%; cordyceps sinensis extract 0.05%; soil minerals 0.1%; lavender oil 0.1%; solid nitric oxide 0.05%.

[0014] A low-temperature curing preparation process of an eye-care patch based on solid nitric oxide slow release, comprising the steps of:

[0015] S100, passing gaseous NO into a -40 DEG C condensation cavity for solidification to form solid NO;

[0016] S200, mixing the solid NO with mineral oil and plant extract into a slurry;

[0017] S300, coating the slurry on non-woven fabric;

[0018] S400, vacuum freeze-drying and shaping.

[0019] An application of an eye-care patch based on solid nitric oxide slow release, which is used as a nursing device for relieving visual fatigue, improving retinal microcirculation or preventing vision impairment.

[0020] An application of an eye-care patch based on solid nitric oxide slow release, which is made into a cervical vertebra patch or a nose patch by using the environmentally friendly non-woven fabric carrier loaded with active ingredients.

[0021] Compared with the prior art, the present application has the following beneficial effects:

[0022] Through the innovative low-temperature curing process (-40 DEG C pulse condensation + vacuum gradient freeze-drying), gaseous nitric oxide is converted into solid microcrystals with a particle size of 1-10 microns, which are stably loaded on a gradient-pore non-woven fabric carrier, combined with a mineral oil-menthol-cordyceps sinensis ternary synergistic system, and three breakthrough effects are achieved: long-acting slow release: solid NO is continuously released for more than 24 hours (cumulative release rate 88%), and the transdermal absorption rate is increased by 300% compared with traditional NO donors; targeted synergistic effect: precise regulation of retinal microcirculation through choroid penetration, clinical verification of 50.4% increase in ophthalmic arterial blood flow velocity, and 33.3% reduction in visual fatigue relief time (18 minutes for taking effect); stable mass production: breaking through the bottleneck of industrial application of gaseous NO, NO residual rate ≥95% in the production process, realizing zero-volatilization coating and 3-hour rapid freeze-drying, and being the first solid NO eye delivery system that can be mass-produced in the world. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 The process flowchart in the present application. DETAILED DESCRIPTION

[0024] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application.

[0025] An eye protection patch based on solid nitric oxide slow release, which is composed of the following components in percentage by mass:

[0026] An environmentally friendly non-woven fabric carrier and active ingredients loaded thereon:

[0027] Mineral oil 30-40%; ginger extract 0.5-2%; menthol 3-8%; cordyceps sinensis extract 0.01-0.1%; soil minerals 0.05-0.2%; lavender oil 0.05-0.3%; solid nitric oxide 0.01-0.1%.

[0028] A low-temperature curing preparation process of an eye protection patch based on solid nitric oxide slow release, comprising the steps of: S100, gaseous NO is introduced into a -40℃ condensation cavity for curing to form solid NO; S200, solid NO is mixed with mineral oil and plant extract to form a slurry; S300, the slurry is coated on non-woven fabric; S400, vacuum freeze-drying is performed for shaping. Specifically:

[0029] Gaseous NO low-temperature curing: in an inert environment with oxygen content ≤5 ppm, gaseous NO is introduced into a condensation cavity at -50℃ to -30℃, and pulse-type gas inlet (5s ventilation / 10s pause, repeated 3 times) is adopted to obtain solid NO microcrystals with particle size of 1-10 μm; slurry gradient mixing: under argon protection, mineral oil is heated to 40℃→ginger extract is added→solid NO microcrystals are added→other ingredients such as menthol are mixed at low speed, first sheared at 2000 rpm for 10 min, and then stirred at 500 rpm for 15 min; low-temperature coating: the slurry is coated on a gradient-pore-size non-woven fabric (surface layer 5 μm / bottom layer 20 μm) at -15℃ environment, the coating thickness is 0.30±0.02 mm, and the temperature is monitored online by infrared to be ≤-10℃; vacuum freeze-drying: pre-freezing stage: -45℃ to -10℃, cooling rate 2℃ / min; main drying: -10℃ / 10 Pa, dew point ≤-40℃; desorption drying: 25℃ / 1 Pa, to water content ≤3%.

[0030] In step S100, the equipment requirements are:

[0031] Stainless steel condensation cavity (inner wall polished to Ra≤0.8 μm to prevent NO adsorption); liquid nitrogen circulating refrigeration system (temperature control accuracy ±1℃); vacuum sealed pipeline (oxygen content ≤10 ppm).

[0032] Operation procedure: high-purity nitrogen (99.99%) was introduced into the condensation cavity to replace air, and the operation was repeated 3 times until the oxygen content was less than 5 ppm; gaseous NO (purity ≥ 99.9%) was injected, and the flow rate was controlled to be 5 L / min; the cavity temperature was reduced to-40℃±2℃ by starting the liquid nitrogen circulation, and maintained for 30 minutes to completely solidify NO; the formation of uniform microcrystals (particle size 1-10 μm, detected by microscope) was observed through the cavity observation window.

[0033] In step S400, it is divided into three stages, as shown in the following table:

[0034] Stage Temperature / pressure Time Purpose Pre-freezing -45°C→-10°C (gradient cooling) 60 min Fixing slurry microstructure Main drying -10°C, 10 Pa 90 min Sublimation of free water Desorption drying 25°C, 1 Pa 30 min Removal of bound water (to moisture content ≤3%)

[0035] Verification: sampling detection: HPLC-fluorescence method was used to detect the NO content after drying, and the requirement was that the residual rate was ≥95% (compared with the initial loading amount).

[0036] The application will be further described below through specific examples.

[0037] Example 1

[0038] Clinical effect verification of the optimal formula of the application:

[0039] Test subjects: 60 long-term electronic screen users (age 25-45 years old), randomly divided into 3 groups:

[0040] Experimental group: eye protection stickers containing 0.05% solid NO were used;

[0041] Control group 1: commercially available menthol eye stickers (without NO);

[0042] Control group 2: eye stickers containing 0.05% nitroglycerin (NO donor).

[0043] Test method:

[0044] The eye stickers were used once a day, each time for 30 minutes, for 14 days;

[0045] Detection index:

[0046] Ocular arterial blood flow velocity (color Doppler ultrasound, unit: cm / s);

[0047] Visual fatigue score (VFS-16 scale, 0-100 points, the lower the score, the better);

[0048] Tear film stability (tear film break-up time TBUT, unit: seconds).

[0049] The data results are shown in Table 1 below:

[0050] Table 1

[0051] Detection index Experimental group (average) Control group 1 (average) Control group 2 (average) P value (experimental group vs. control) Ocular arterial blood flow velocity↑ 18.2 cm / s 12.1 cm / s 14.5 cm / s <0.01 Visual fatigue score↓ 32.5 points 48.7 points 41.2 points <0.001 Tear film stability (TBUT)↑ 12.3 seconds 8.5 seconds 9.8 seconds <0.01

[0052] According to Table 1 above, the experimental group improved the ophthalmic artery blood flow velocity by 50.4% (P < 0.01) compared with the control group 1 and by 25.5% compared with the NO donor group, proving that the solid-state NO slow-release technology has a significant advantage in improving the ocular microcirculation. In the visual fatigue score, the experimental group reduced the score to 32.5 points, which was 33.3% lower than the control group 1 (48.7 points) (P < 0.001) and better than the NO donor group (41.2 points). Combined with user feedback, it is attributed to the synergistic effect of NO and menthol: NO dilates blood vessels to increase oxygen supply, and menthol promotes ingredient penetration and instant cooling analgesia. The improvement of tear film stability (TBUT = 12.3 seconds in the experimental group) indicates that NO indirectly enhances the function of lacrimal glands by improving the blood circulation of the ocular surface, breaking through the limitations of traditional eye patches that only rely on moisturizing ingredients.

[0053] Example 2

[0054] Study the effect of process temperature on NO slow-release efficiency: as shown in Table 2 below.

[0055] Table 2

[0056] Process temperature NO initial loading (mg / cm²) 24h release rate (%) 48h cumulative release rate (%) -50℃ 0.51 38% 85% -40℃ 0.49 42% 88% -30℃ 0.47 50% 92% -20°C (comparative example) 0.32 82% 98% (depleted within 12h)

[0057] According to Table 2 above, when the curing temperature is ≤-30°C, NO forms a stable microcrystalline structure on the non-woven fabric (SEM detection shows a particle size of 1-5 μm), and the 24-hour release rate is controlled between 38-50%, achieving long-acting slow release. The-20°C group is insufficient due to insufficient temperature, and NO condensation is not sufficient (particle size > 20 μm), resulting in rapid volatilization after coating, with a 48-hour cumulative release rate of up to 98%, which cannot meet the continuous penetration requirements of the eye. Therefore, -40°C is the optimal process node (balance of energy consumption and effect), with a 24-hour release rate of 42% and a 48-hour cumulative release rate of 88%, which precisely matches the 8-hour / day usage cycle of eye care.

[0058] Example 3

[0059] Referring to the penetration experiment in Table 3 below, Group A: 0.05% solid-state NO + 5% menthol, Group B: 0.05% solid-state NO (without menthol), Group C: 5% menthol (without NO); Group D: blank non-woven fabric.

[0060] Time Group A Group B Group C Group D 0-2h 1.25 0.60 0.01 0 2-8h 0.85 0.35 0 0 8-24h 0.40 0.10 0 0

[0061] Table 3

[0062] From Table 3, the NO permeation rate of Group A in 0-2 hours reached 1.25 μg / cm2·h, which was 2.08 times of that of Group B (without menthol), proving that menthol as a penetration enhancer significantly improved the initial penetration efficiency of NO. In the 8-24 hour stage, Group A still maintained a release of 0.4 μg / cm2·h, while Group B decreased to 0.1 μg / cm2·h, indicating that the lipid microenvironment formed by mineral oil (35%) and cordyceps sinensis extract (antioxidant) together maintained the stability of NO.

[0063] The above examples are only used to illustrate the technical solutions of the present application, but not limit it.

Claims

1. An eye care patch based on solid nitric oxide sustained release, characterized in that, By the following components by mass percentage: An environmental non-woven fabric carrier, and active ingredients loaded thereon: Mineral oil 30-40%; ginger extract 0.5-2%; menthol 3-8%; cordyceps extract 0.01-0.1%; soil minerals 0.05-0.2%; lavender oil 0.05-0.3%; solid nitric oxide 0.01-0.1%.

2. The eye protection patch based on solid nitric oxide release according to claim 1, characterized in that, The solid nitric oxide is prepared by a low-temperature solidification process: Condensing gaseous NO into solid particles with a particle size of 1-10 μm at an environment of-50℃ to-30℃; Mixing the solid NO particles with the remaining ingredients and coating them on non-woven fabric; Vacuum freeze-drying and setting for 2 hours at a temperature of-45℃ and a pressure of 10 Pa.

3. The eye protection patch based on solid nitric oxide release according to claim 2, characterized in that, The condensing temperature is-40℃±2℃.

4. The eye protection patch based on solid nitric oxide release according to claim 1, characterized in that, The mass percentage of the active ingredients is: Mineral oil 35%; ginger extract 1%; menthol 5%; cordyceps extract 0.05%; soil minerals 0.1%; lavender oil 0.1%; solid nitric oxide 0.05%.

5. A low temperature solidification process for the preparation of an eye care patch based on solid nitric oxide release according to any one of claims 1 to 4, characterized in that, The steps include: S100, passing gaseous NO into a-40℃ condensing cavity for solidification to form solid NO; S200, mixing the solid NO with mineral oil and plant extract into slurry; S300, coating the slurry on non-woven fabric; S400, vacuum freeze-drying and setting.

6. The use of a solid nitric oxide sustained-release based eye care patch according to any one of claims 1-4, characterized in that, A care device for relieving visual fatigue, improving retinal microcirculation, or preventing vision impairment.

7. The use of an eye-protecting patch based on solid nitric oxide slow release according to any one of claims 1-4, characterized in that, The environmental non-woven fabric carrier carrying the active ingredients is made into cervical vertebrae patches and nose patches.

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