Eye protection liquid for improving eye microcirculation and preparation method thereof

Abstract

The invention provides eye protection liquid for improving eye microcirculation and a preparation method thereof, and belongs to the technical field of medical configuration products. The composition comprises the following components: surface-modified magnetic nanoparticles, a calendula extract, a fermented dogwood extract, xanthophyll, taurine, sodium hyaluronate, hydrolyzed sodium hyaluronate, soya bean lecithin, borneol and fermented vegetable oil. The efficiency of active ingredients is improved through a double-fermentation technology, magnetic targeting and multi-channel compounding are combined, and the preparation method has remarkable advantages in the field of improving periorbital microcirculation. The traditional Chinese medicine composition has an obvious relieving effect on asthenopia and dry skin around eyes; the components of the eye microcirculation eye protection liquid are mild, and adverse reactions such as allergy cannot be caused.

Description

Technical Field

[0001] The invention belongs to the technical field of medical preparations, and in particular relates to an eye protection solution for improving eye microcirculation and a preparation method thereof. Background Art

[0002] The functional state of the ocular microcirculation directly determines the health of the visual system. Anatomically, the ocular microcirculatory system consists of the short posterior ciliary arteries, the central retinal artery, and its branches. Through a network of capillaries approximately 10 microns in diameter, it delivers oxygen and nutrients to retinal nerve cells, the lens, the cornea, and other tissues, while also metabolizing carbon dioxide and metabolic waste. This sophisticated vascular network requires a blood flow exchange of approximately 0.3 ml / g of tissue per second to maintain the normal electrophysiological activity of retinal photoreceptor cells. Insufficient microcirculatory perfusion triggers a cascade of pathological reactions.

[0003] Modern lifestyles are systematically disrupting ocular microcirculatory homeostasis. Among people who use electronic devices for more than 6 hours a day, 72% experience a slowing of ophthalmic artery blood flow (Doppler ultrasound shows that the flow rate is 18-25 cm / s lower than normal). Blue light radiation can induce vascular endothelial cell damage by activating the NLRP3 inflammasome in retinal pigment epithelial cells; and the increased chest pressure caused by long-term sitting can increase the resistance of ophthalmic venous return by more than 40%, forming a state of "ocular blood stasis". Microcirculatory disorders are the common pathological basis of many eye diseases. In the pathogenesis of dry eye, microcirculatory disorders around the meibomian gland alveoli can lead to hypoxia of lipid-secreting cells, reducing the stability of the tear film; in the early stages of diabetic retinopathy, the first thing that appears is capillary occlusion caused by pericyte apoptosis, which then develops into microaneurysms and neovascularization.

[0004] Existing eye protection methods have significant limitations. Commercially available anti-fatigue eye drops often contain vasoconstrictors, which, while temporarily relieving red eyes, can worsen microcirculatory disorders due to vasospasm. Physical therapies such as hot compresses only temporarily increase local temperature and fail to address the underlying issue of endothelial dysfunction.

[0005] From the perspective of physiological necessity, the high metabolic characteristics of eye tissue (retinal oxygen consumption accounts for 15% of the whole body) determine its high dependence on microcirculation; from the perspective of disease prevention, improving microcirculation can play a key role in myopia control, dry eye prevention and treatment, early intervention of diabetic retinopathy and other fields. Summary of the Invention

[0006] The object of the present invention is to provide an eye protection liquid for improving eye microcirculation and a preparation method thereof in response to the above problems.

[0007] Ingredients calculated in percentages:

[0008]

[0009]

[0010] The fermented cornus officinalis extract is obtained by fermenting cornus officinalis with Bacillus subtilis and then purifying it;

[0011] The fermented vegetable oil is obtained by fermenting vegetable oil with Candida albicans produced by bumblebees and then purifying the fermented vegetable oil.

[0012] Preferably, the vegetable oil is at least one of jojoba oil and sweet almond oil.

[0013] Preferably, vegetable oil is mixed with an aqueous medium to form a fermentation substrate and inoculated with activated Candida bumblebee; and then fermented at 28-32°C, pH 5.0-6.0, and an OD value of at least 40% for at least 72 hours;

[0014] After fermentation, the mixture is sterilized and centrifuged to obtain the upper oil phase; the oil phase is dehydrated and then molecularly distilled to collect the main fraction at 160-180°C.

[0015] Preferably, the aqueous culture medium contains at least the following components in percentage by mass:

[0016] At least 1% yeast extract;

[0017] At least 2% glucose

[0018] At least 1% peptone

[0019] At least 0.1% magnesium sulfate

[0020] At least 2.5% of a nonionic lipophilic emulsifier.

[0021] Preferably, the preparation method of the fermented cornus extract is as follows: taking cornus fruit, removing the core, crushing and sieving, and then sterilizing;

[0022] After sterilization, the product is enzymatically hydrolyzed with pectinase and cellulase; after enzymatic hydrolysis, the enzyme is inactivated and the filtrate is filtered to obtain the filtrate;

[0023] The filtrate is inoculated with activated Bacillus subtilis and aerobically fermented at 37-40°C, pH 6.2-6.7, and a ventilation rate of 0.6-1.0 vvm for at least 48 hours;

[0024] After fermentation, the product is sterilized and centrifuged to obtain the supernatant, which is then passed through an 800Da filter membrane. The filtered solution is then dried to form a solid.

[0025] Preferably, during the aerobic fermentation of the filtrate, an auxiliary carbon source, an auxiliary nitrogen source, dipotassium hydrogen phosphate and manganese sulfate are added.

[0026] Preferably, when enzymatic hydrolysis is performed using pectinase and cellulase, the temperature is controlled at 45-50° C. and the pH is 4.5-5.5.

[0027] Preferably, the following components are also included:

[0028] Phenoxyethanol 0.2-0.6%

[0029] Disodium EDTA 0.01-0.05%

[0030] The present invention also provides the use of the above-mentioned eye protection liquid for improving eye microcirculation in the preparation of medical supplies.

[0031] In this invention, the fermented Cornus officinalis extract alleviates dry eye symptoms by inhibiting the NF-κB pathway, reducing the expression of inflammatory factors such as IL-1β, IL-6, and TNF-α. It also improves periocular microcirculation, alleviating visual fatigue and blurred vision. The Cornus officinalis extract is fermented with Bacillus subtilis to enhance the bioavailability of iridoid glycosides (such as morroniside), and is purified by ultrafiltration to enhance transdermal absorption.

[0032] The content of free fatty acids and phytosterols in fermented vegetable oil increases, which repairs the lipid layer on the ocular surface and reduces tear evaporation.

[0033] Surface-modified magnetic nanoparticles precisely locate the capillaries around the eyes under the guidance of the external magnetic field, thereby increasing the local concentration of the drug; inducing the recovery of the negative charge on the surface of red blood cells, disaggregating adhered cells, and increasing blood oxygen supply.

[0034] Flavonoids in calendula extract (such as quercetin) inhibit inflammatory factors such as TNF-α and IL-6, and relieve conjunctival congestion; in addition, its polysaccharide components promote corneal epithelial cell adhesion and accelerate wound healing.

[0035] The effects of lutein, taurine, etc. are relatively clear and common, so I will not go into details.

[0036] Large-molecule sodium hyaluronate forms a film on the ocular surface, and small-molecule hydrolyzed sodium hyaluronate penetrates deep into the cornea; it has a long-lasting moisturizing effect; at the same time, it can activate CD44 receptors and promote corneal epithelial migration.

[0037] Soy lecithin phosphatidylcholine integrates into damaged cell membranes, restoring barrier integrity; it also acts as a surfactant.

[0038] The ingredients in this invention have the following synergistic effects:

[0039] Targeted delivery and enhanced penetration: Magnetic nanoparticles and borneol open intercellular spaces, allowing the magnetic particles to penetrate deep into the ciliary capillaries under the guidance of a magnetic field. Soy lecithin and lutein lecithin liposomes enhance lutein solubility and facilitate transcorneal transport.

[0040] Synergistic anti-inflammatory and microcirculatory improvement: Calendula and fermented Cornus officinalis: Calendula's anti-inflammatory effects inhibit vascular leakage, while cornusin directly dilates blood vessels. Fermented vegetable oil and taurine: Gamma-linolenic acid in vegetable oil downregulates prostaglandin PGE2, while taurine regulates osmotic pressure, jointly alleviating angioedema.

[0041] Synergy of antioxidant and light damage protection: Lutein and Cornus officinalis ferment: Lutein neutralizes singlet oxygen induced by blue light, and Cornus officinalis iridoid glycosides scavenge mitochondrial superoxide anions, forming a dual antioxidant chain.

[0042] Moisturizing and repairing synergy: Sodium hyaluronate and fermented plant oil: large molecule hyaluronic acid locks in moisture, small molecule hyaluronic acid penetrates and repairs, and the sterols in the fermented oil repair the lipid barrier, achieving "surface-deep" three-dimensional moisturizing.

[0043] This invention utilizes dual fermentation technology to enhance the potency of active ingredients, combined with magnetic targeting and multi-pathway compounding, offering significant advantages in improving periocular microcirculation. It significantly relieves visual fatigue and dry skin around the eyes. The ingredients in this eye microcirculation eye protection solution are mild and will not cause allergic reactions. DETAILED DESCRIPTION

[0044] In the description of the present invention, the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly specify the number of the technical features indicated. Therefore, a feature specified as "first" or "second" may explicitly or implicitly include one or more of the specified features. In the description of the present invention, "plurality" means two or more, unless otherwise specifically defined.

[0045] In the description of the present invention, the term "for example" is used to mean "used as an example, illustration or illustration". Any embodiment of the present invention described as "for example" is not necessarily to be construed as being more preferred or advantageous than other embodiments. The following description is given to enable any person skilled in the art to implement and use the present invention. In the following description, details are listed for the purpose of explanation. It should be understood that a person of ordinary skill in the art can recognize that the present invention can be implemented without using these specific details. In other examples, well-known structures and processes are not elaborated in detail to avoid obscuring the description of the present invention with unnecessary details. Therefore, the present invention is not intended to be limited to the embodiments shown, but is consistent with the widest scope consistent with the principles and features disclosed herein.

[0046] Unless otherwise specified, the experimental methods used in the specific embodiments are all conventional methods, and the materials, reagents, etc. used are all commercially available unless otherwise specified.

[0047] In the present invention, unless otherwise specified, “%” represents mass percentage; the raw materials, reagents, etc. used are conventional commercial products.

[0048] In the present invention, the water used is preferably pure water (RO water).

[0049] Some of the raw materials used in the present invention are as follows:

[0050] Surface-modified magnetic nanoparticles: chitosan-coated ferroferric oxide nanoparticles

[0051] Bombus-derived Candida: scientific name Starmerella bombicola

[0052] Bacillus subtilis: Latin name L. rhamnosus

[0053] Jojoba oil: jojoba (SIMMONDSIA CHINENSIS) seed oil

[0054] Sweet almond oil: Sweet almond oil, also known as sweet almond (PRUNUS AMYGDALUS ULCIS) oil

[0055] Calendula extract: Calendula officinalis flower extract

[0056] Cornus officinalis: refers to Cornus officinalis.

[0057] Example 1

[0058] The preparation of the fermented cornus officinalis extract comprises the following steps:

[0059] S1: Take fresh Cornus officinalis fruit, wash it, remove the core, crush it, sieve it at low temperature to a particle size of 10 mesh, and then sterilize it;

[0060] S2: Cellulase (20 U / g artichoke leaf) and pectinase (15 U / g artichoke leaf) were mixed; the solid-liquid ratio was adjusted to 1:8 (adjusted with water) and enzymatic hydrolysis was carried out at 45-50°C and pH 4.5-5.0 (adjusted with citric acid) for 2 h;

[0061] After the enzymatic hydrolysis was completed, the temperature was raised to 85°C and maintained for 10 minutes to inactivate the enzyme; the filtrate was collected by centrifugation (3000 g, 15 minutes).

[0062] S3: Prepare the substrate according to the following ratio and add an appropriate amount of sterile water to adjust the water content; prepare the activated Bacillus subtilis into 1×10 7 The suspension of CFU / mL was inoculated at a ratio of 5%, and then cultured according to the following conditions.

[0063] Substrate composition:

[0064] 100 parts of filtrate, 2 parts of glucose, 1 part of yeast extract powder, 0.5 parts of casein peptone, 0.5 parts of beef extract powder, 0.75 parts of dipotassium hydrogen phosphate, 0.05 parts of manganese sulfate, and 0.1 parts of Tween 80.

[0065] Fermentation conditions: temperature 37-40°C, pH 6.2-6.7, ventilation rate 0.6-0.8 vvm in the first 24 hours, 0.8-1.0 vvm after 24 hours; aerobic fermentation for 48 hours.

[0066] S4: After the fermentation is completed, the fermentation is sterilized and centrifuged to obtain the supernatant, which is then passed through an 800Da filter membrane. The filtered solution is then dried to form a solid.

[0067] Example 2

[0068] The preparation of fermented vegetable oil comprises the following steps:

[0069] S1: Different oils were mixed with aqueous medium in a 1:1 volume ratio and homogenized by a microfluidizer, and then sterilized by autoclaving at 121°C for 20 min to prepare the fermentation substrate.

[0070] The aqueous medium contains the following ingredients: 1% yeast extract, 2% glucose, 1% peptone, 0.1% magnesium sulfate, 2.5% Span 80; the balance is deionized water;

[0071] S2: fermentation of substrate and inoculation with activated Candida bombus;

[0072] Fermentation was carried out at 28-32°C, pH 5.0-6.0, OD value ≥ 40%, and aeration of 0.6 vvm for 72 h;

[0073] S3: After fermentation, the mixture was inactivated at 100°C for 15 min, followed by centrifugation at 9000 g for 20 min to collect the upper oil phase. The oil phase was vacuum dehydrated, and the main fraction at 160–180°C was collected by molecular distillation.

[0074] Example 3

[0075] The preparation of eye protection solution for improving ocular microcirculation comprises the following steps:

[0076] S1: Weigh each component as described in Table 1 below;

[0077] S2: Mix all components evenly and store in sealed container.

[0078] Table 1 Eye drops for improving eye microcirculation

[0079]

[0080]

[0081] Table 1 (Continued) Eye drops for improving eye microcirculation

[0082] Raw material (mass percentage) / serial number 5 6 7 8 Surface-modified magnetic nanoparticles 0.10 0.10 0.10 0.10 Calendula extract 1.0 1.0 1.0 0 Fermented Cornus officinalis extract 2 0 0 3 Commercially available Cornus officinalis extract 0 2 2 0 Lutein 0.10 0.10 0.10 0.10 Taurine 0.30 0.30 0.30 0.30 Sodium hyaluronate 0.05 0.05 0.05 0.05 Hydrolyzed sodium hyaluronate 0.01 0.01 0.01 0.01 Soy lecithin 0.2 0.2 0.2 0.2 borneol 0.01 0.01 0.01 0.01 Fermented jojoba oil 0 1 0 1 Fermented sweet almond oil 0 0 0 0 Jojoba oil (commercially available) 0 0 1 0 Sweet almond oil (commercially available) 1 0 0 0 Phenoxyethanol 0 0 0 0 Disodium EDTA 0 0 0 0 water to 100% to 100% to 100% to 100%

[0083] Eye irritation test

[0084] The eye irritation of the samples prepared in Example 3 to rabbits was examined by the Draize eye irritation test. The eyes of the rabbits were observed after continuous administration, and the results showed that there was no secretion or congestion; all samples were non-irritating.

[0085] Experimental study on the effect of tear secretion on dry eye model rats

[0086] Grouping: D1, 45 rats with qualified corneal fluorescence staining scores and tear secretion were selected and divided into 9 groups (model control group and 8 experimental groups), with 5 rats in each group and no significant statistical difference.

[0087] Modeling: On D2, 20 μL of hypertonic solution was instilled into the conjunctival sac of both eyes of the animal, 5 times / day, with an interval of about 2 hours between each instillation, for 27 consecutive days. After instillation, the animal's eyelids were passively closed for about 90 seconds to establish the model.

[0088] Administration: The model control group received no additional medication, while the experimental groups were administered the eye protection solutions prepared in Example 3 (sprayed 12 times a day, approximately equivalent to 3 times the clinical dosage) for 20 consecutive days.

[0089] Test: The tear secretion (mm2) of each group of rats was measured on D10 and D20, and the mean was calculated. The results are shown in Table 2.

[0090] Table 2 The results of tear secretion measurement of each group of rats

[0091]

[0092]

[0093] The results in Table 2 show that after 20 days of continuous administration, the tear secretion of rats with samples No. 1-3 in Example 3 essentially returned to normal, effectively treating dry eye in rats. Furthermore, as the active ingredient content in the samples increased, the therapeutic rate also increased. Sample No. 4 used commercial jojoba oil, and Sample No. 5 used commercial sweet almond oil instead of the fermented jojoba oil in Sample No. 1. The therapeutic efficacy was significantly reduced, demonstrating the necessity of the fermentation step in the present invention. Similarly, Sample No. 6 used commercial Cornus officinalis extract instead of the fermented Cornus officinalis extract in Sample No. 1, and the therapeutic efficacy was even more significantly reduced. Sample No. 7, which used both commercial jojoba oil and Cornus officinalis extract, showed an even further decline in therapeutic efficacy. This indicates that the Cornus officinalis fermentation step in the present invention has a more significant impact on the therapeutic efficacy than the fermentation of vegetable oils. Sample No. 8 removed the Calendula officinalis extract and replaced it with an equal amount of fermented Cornus officinalis extract. However, its therapeutic efficacy was somewhat reduced compared to Sample No. 1, demonstrating the synergistic effect of the Calendula officinalis extract and the fermented Cornus officinalis extract.

[0094] The above detailed description is a specific description of one feasible embodiment of the present invention. This embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. An eye protection solution for improving eye microcirculation, characterized in that: Ingredients calculated in percentages: The fermented cornus officinalis extract is obtained by fermenting cornus officinalis with Bacillus subtilis and then purifying it; The fermented vegetable oil is obtained by fermenting vegetable oil with Candida albicans produced by bumblebees and then purifying the fermented vegetable oil.

2. The eye protection solution for improving eye microcirculation according to claim 1, characterized in that: The vegetable oil is at least one of jojoba oil and sweet almond oil.

3. The eye protection solution for improving eye microcirculation according to claim 1, characterized in that: The method for preparing the fermented vegetable oil comprises: taking vegetable oil, mixing and emulsifying it with an aqueous medium to prepare a fermentation substrate, and inoculating it with activated Candida bumblebee; and then fermenting it for at least 72 hours at 28-32° C., pH 5.0-6.0, and an OD value of at least 40%. After fermentation, the oil phase is sterilized and centrifuged to obtain the upper oil phase; the oil phase is dehydrated and then molecularly distilled to collect the main fraction at 160-180°C.

4. The eye protection solution for improving eye microcirculation according to claim 3, characterized in that: The aqueous culture medium contains at least the following components in percentage by mass: At least 1% yeast extract; At least 2% glucose At least 1% peptone At least 0.1% magnesium sulfate At least 2.5% of a nonionic lipophilic emulsifier.

5. The eye protection solution for improving eye microcirculation according to claim 1, characterized in that: The preparation method of the fermented cornus officinalis extract comprises the following steps: taking cornus officinalis fruits, removing the core, crushing and sieving, and then sterilizing; After sterilization, the product is enzymatically hydrolyzed with pectinase and cellulase; after enzymatic hydrolysis, the enzyme is inactivated and the filtrate is filtered to obtain the filtrate; The filtrate is inoculated with activated Bacillus subtilis and aerobically fermented at 37-40°C, pH 6.2-6.7, and a ventilation rate of 0.6-1.0 vvm for at least 48 hours; After fermentation, the product is sterilized and centrifuged to obtain the supernatant, which is then passed through an 800Da filter membrane. The filtered solution is then dried to form a solid.

6. The eye protection solution for improving eye microcirculation according to claim 5, characterized in that: During the aerobic fermentation of the filtrate, an auxiliary carbon source, an auxiliary nitrogen source, dipotassium hydrogen phosphate and manganese sulfate are added.

7. The eye protection solution for improving eye microcirculation according to claim 5, characterized in that: When using pectinase and cellulase for enzymatic hydrolysis, the temperature is controlled at 45-50°C and the pH is 4.5-5.

5.

8. The eye protection solution for improving eye microcirculation according to claim 1, characterized in that: Also includes the following components: Phenoxyethanol 0.2-0.6% Disodium EDTA 0.01-0.05%.

9. Use of the eye protection solution for improving ocular microcirculation according to claims 1-8 in the preparation of medical supplies.

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