Astaxanthin composition for treating dry eye, method of preparing the same, and use thereof

Abstract

The present application belongs to the field of dry eye treatment, and relates to a astaxanthin composition for treating dry eye, a preparation method and application thereof. The astaxanthin composition comprises 25-35 parts of astaxanthin, 20-30 parts of algal polysaccharide, 5-10 parts of salidroside, 2-3 parts of menthol, 1-2 parts of borneol and 0.5-1 part of lutein according to weight. The composition of the present application comprises astaxanthin, algal polysaccharide, salidroside, menthol, borneol and lutein. These components act together, especially the synergistic effect of astaxanthin, algal polysaccharide and salidroside, so that the composition has remarkable curative effect in treating dry eye and can effectively relieve the symptoms of dry eye. In addition, compared with some artificially synthesized drugs, the components of the composition of the present application come from natural biomass, which is safer and has low side effects when used.

Description

Technical Field

[0001] This invention relates to the field of dry eye treatment technology, specifically to an astaxanthin composition for treating dry eye, its preparation method, and its application. Background Technology

[0002] Dry eye syndrome is a common eye condition characterized by insufficient tear production, excessive evaporation, or abnormal tear composition. Symptoms include eye pain, a foreign body sensation, blurred vision, and dryness. In severe cases, patients may experience burning, soreness, redness, pain, and photophobia. Therefore, timely and effective treatment of dry eye syndrome is necessary.

[0003] With changes in modern lifestyles, prolonged use of electronic screens and air-conditioned environments have exacerbated the incidence of dry eye syndrome. Currently, the main treatment methods for dry eye syndrome include the following:

[0004] 1. Artificial tears eye drops: This is the most common way to relieve symptoms by replenishing tears to reduce dryness and discomfort in the eyes.

[0005] 2. Oral medications: Some oral medications can increase tear secretion or improve tear quality.

[0006] While the above treatments can alleviate the symptoms of dry eye to some extent, they also have limitations and side effects. For example, long-term use of artificial tears may put a burden on the cornea, and oral medications may cause adverse reactions.

[0007] Astaxanthin is widely found in the biological world and is one of the main carotenoids in marine organisms. Astaxanthin is one of the strongest known antioxidants, with an antioxidant capacity far exceeding that of other antioxidants such as vitamin E and beta-carotene. It can scavenge free radicals, protect cells from oxidative damage, enhance the body's immunity, and slow down skin aging. In the eye area, astaxanthin is mostly used to relieve eye strain and prevent myopia; current technology rarely uses astaxanthin to treat dry eye syndrome.

[0008] Therefore, there is a need to develop a product containing astaxanthin that can effectively treat dry eye syndrome and reduce side effects. Summary of the Invention

[0009] (a) Technical problems to be solved

[0010] To address the problems of poor treatment efficacy and side effects of existing technologies for treating dry eye syndrome using artificial tears and oral medications, this invention provides an astaxanthin composition for treating dry eye syndrome, its preparation method, and its application.

[0011] (II) Technical Solution

[0012] To achieve the above objectives, the main technical solutions adopted by the present invention include:

[0013] In a first aspect, the present invention provides an astaxanthin composition for treating dry eye syndrome, comprising, by weight, 25-35 parts astaxanthin, 20-30 parts seaweed polysaccharide, 5-10 parts rhodioloside, 2-3 parts menthol, 1-2 parts borneol and 0.5-1 parts lutein; wherein the astaxanthin is encapsulated by nanoliposomes.

[0014] The astaxanthin composition for treating dry eye as described above preferably comprises, by weight, 30 parts astaxanthin, 25 parts seaweed polysaccharide, 8 parts rhodioloside, 3 parts menthol, 2 parts borneol and 1 part lutein.

[0015] The astaxanthin composition for treating dry eye syndrome as described above preferably also includes 1-2 parts of vitamin C.

[0016] Secondly, the present invention provides a method for preparing the above-mentioned astaxanthin composition, comprising the following steps:

[0017] S1: Provides astaxanthin encapsulated in nanoliposomes;

[0018] S2: Mix seaweed polysaccharide, rhodioloside, menthol, borneol and lutein to obtain a mixture;

[0019] S3: Astaxanthin encapsulated in nanoliposomes is mixed with the mixture to obtain a composition.

[0020] In the preparation method of the astaxanthin composition as described above, preferably, in step S1, astaxanthin, lecithin and cholesterol are dissolved in an organic solvent, mixed evenly and then the organic solvent is removed to obtain a uniform lipid membrane; then an aqueous solution is added to the lipid membrane to hydrate the lipid membrane, and then ultrasonic treatment is performed to obtain astaxanthin encapsulated by nanoliposomes.

[0021] In the preparation method of the astaxanthin composition as described above, preferably, in step S1, the mass ratio of astaxanthin, lecithin and cholesterol is (200-300):(10-20):(50-100);

[0022] The organic solvent is ethanol; the mixture of astaxanthin, lecithin, cholesterol and organic solvent is subjected to rotary evaporation under reduced pressure of 40-60 mbar and temperature of 40-42℃ to remove the organic solvent.

[0023] In the preparation method of the astaxanthin composition as described above, preferably, in step S1, the aqueous phase solution is a phosphate buffer solution, and the volume-to-mass ratio of the aqueous phase solution to the lipid membrane, v:w, is (2-3) mL:1 g.

[0024] The ultrasonic treatment power is 150-200W, the ultrasonic treatment time is 6-10 minutes, and there is a 20-30 second pause after every 1-2 minutes of treatment.

[0025] Thirdly, the present invention provides the application of the above-mentioned astaxanthin composition or the astaxanthin composition prepared by the above-mentioned preparation method in an eye patch.

[0026] Fourthly, the present invention provides the use of the above-mentioned astaxanthin composition or the astaxanthin composition prepared by any one of claims 4-7 in eye drops or eye ointments.

[0027] Fifthly, the present invention provides the application of the above-mentioned astaxanthin composition or the astaxanthin composition prepared by any one of claims 4-7 in a nasal mucosa ointment.

[0028] (III) Beneficial Effects

[0029] The composition of this invention includes astaxanthin, seaweed polysaccharides, rhodioloside, menthol, borneol, and lutein. These components work synergistically to significantly treat dry eye syndrome and effectively relieve its symptoms. Furthermore, compared to some synthetic drugs, the composition of this invention is derived from natural biomass, making it safer to use and with fewer side effects.

[0030] The astaxanthin, seaweed polysaccharide, and rhodioloside in this invention have a synergistic effect. Compared with one or two single effective components, the combined effect of astaxanthin, seaweed polysaccharide, and rhodioloside ensures that the composition of this invention has a better therapeutic effect on dry eye syndrome. Detailed Implementation

[0031] To better explain and facilitate understanding of the present invention, the present invention will be described in detail below with reference to specific embodiments.

[0032] The present invention provides an astaxanthin composition for treating dry eye syndrome, comprising, by weight, 25-35 parts astaxanthin, 20-30 parts seaweed polysaccharide, 5-10 parts rhodioloside, 2-3 parts menthol, 1-2 parts borneol and 0.5-1 parts lutein.

[0033] Preferably, the astaxanthin composition for treating dry eye syndrome, by weight, includes 30 parts astaxanthin, 25 parts seaweed polysaccharide, 8 parts rhodioloside, 3 parts menthol, 2 parts borneol, and 1 part lutein, and may also include 1-2 parts vitamin C.

[0034] The functions of each component in the astaxanthin composition of the present invention are as follows:

[0035] Astaxanthin: As a powerful antioxidant, it can scavenge free radicals, protect eye cells from free radical damage, reduce eye inflammation, maintain the integrity of the eye barrier, and accelerate the repair of eye tissues.

[0036] Seaweed polysaccharides: possess natural antioxidant properties, provide excellent moisturizing effects, help maintain a moist environment around the eyes, form a protective film around the eyes, reduce water evaporation, thereby increasing the stability of the tear film, and also help build and strengthen the eye barrier, promoting the repair of eye tissues.

[0037] Rhodioloside: It has anti-fatigue and immunomodulatory effects, helps reduce eye inflammation, and can also improve the health of eye tissues by enhancing local blood circulation and nutrient supply, and enhance the eye barrier's defense mechanism through immunomodulatory effects.

[0038] Menthol and borneol: can bring a cooling sensation, relieve eye discomfort, and also have a certain anti-inflammatory effect.

[0039] Lutein: It can protect retinal cells, prevent macular degeneration, and also has antioxidant and anti-inflammatory effects.

[0040] The astaxanthin composition of this invention exhibits significant efficacy in treating dry eye syndrome due to the synergistic effect of its multiple components, effectively alleviating the symptoms. Compared to some synthetic drugs, the composition of this invention is derived from natural biomass, making it safer to use and resulting in fewer side effects.

[0041] The astaxanthin, seaweed polysaccharide, and rhodioloside in this invention have a synergistic effect. Compared with one or two single effective components, the combined effect of astaxanthin, seaweed polysaccharide, and rhodioloside ensures that the composition of this invention has a better therapeutic effect on dry eye syndrome. The absence of any one or two of these components will reduce the therapeutic effect on dry eye syndrome.

[0042] Although astaxanthin is a potent antioxidant, it is sensitive to light, heat and oxygen and is easily degraded. Therefore, more preferably, the astaxanthin in the above-mentioned astaxanthin composition can be encapsulated by nanoliposomes.

[0043] Nanoliposomes can provide a stable microenvironment for astaxanthin, protecting it from external factors and extending its shelf life and duration of use. Furthermore, nanoliposomes can achieve sustained release of astaxanthin, allowing it to be gradually released into the eye for a continuous effect, reducing the need for frequent dosing. During use, nanoliposomes can also increase the permeability and retention time of astaxanthin in ocular tissues, thereby improving its bioavailability.

[0044] The preparation method of the above-mentioned astaxanthin composition includes the following steps:

[0045] S1: Provides astaxanthin encapsulated in nanoliposomes.

[0046] S2: Mix seaweed polysaccharide, rhodioloside, menthol, borneol, and lutein to obtain a mixture. In this step, seaweed polysaccharide, rhodioloside, menthol, borneol, and lutein can be dissolved in a small amount of deionized water or buffer solution to mix with astaxanthin encapsulated in nanoliposomes.

[0047] S3: Astaxanthin encapsulated in nanoliposomes is mixed with the mixture to obtain a composition.

[0048] Preferably, step S1 specifically includes: dissolving astaxanthin, lecithin and cholesterol in an organic solvent, mixing them evenly and then removing the organic solvent to obtain a uniform lipid membrane, then adding an aqueous solution to the lipid membrane to hydrate the lipid membrane, and then performing ultrasonic treatment to obtain astaxanthin encapsulated by nanoliposomes.

[0049] The mass ratio of astaxanthin, lecithin, and cholesterol was (200-300):(10-20):(50-100), and the organic solvent was ethanol. Specifically, the mixture of astaxanthin, lecithin, cholesterol, and organic solvent was subjected to rotary evaporation under reduced pressure of 40-60 mbar and temperature of 40-42℃ to remove the organic solvent.

[0050] The aqueous solution is preferably a phosphate buffer solution, and the volume-to-mass ratio (v:w) of the aqueous solution to the lipid membrane is (2-3) mL:1 g. In this invention, the lipid membrane is prepared into nanoliposomes by ultrasonic dispersion. The ultrasonic treatment power is 150-200 W, the ultrasonic treatment time is 6-10 min, and there is a 20-30 s pause after every 1-2 min of treatment. The lipid membrane comprises the total weight of lecithin, astaxanthin, and cholesterol.

[0051] As a major component of lipid membranes, lecithin has good biocompatibility. Cholesterol can be inserted into the bilayer structure of lecithin and regulate the fluidity and stability of the membrane through interaction with phospholipid molecules. Cholesterol can make liposome membranes more stable and less prone to rupture, which helps to improve the encapsulation efficiency of astaxanthin and also improves the biocompatibility of nanoliposomes.

[0052] The aqueous solution used in this invention is preferably a phosphate buffer solution. The pH of the phosphate buffer solution is typically around 7.4, which is crucial for maintaining the stability of liposomes and preventing lipid aggregation or degradation. Adding phosphate buffer solution hydrates the lipid membrane, facilitating uniform dispersion of liposomes in the aqueous phase and ensuring a good particle size distribution in the formed liposomes.

[0053] The astaxanthin composition provided by this invention or the astaxanthin composition prepared by the above-described method can be applied to eye patches, eye drops, and eye ointments. Specifically, the necessary raw materials for the preparation of the product can be added to the liquid composition to obtain eye patches, eye drops, and eye ointments. During the preparation of eye patches, eye drops, and eye ointments, potassium sorbate can be added as a preservative, and sodium hyaluronate, which has good water-retention capacity, can also be added. Furthermore, the astaxanthin composition provided by this invention or the astaxanthin composition prepared by the above-described method can be applied to nasal mucosa ointments and can be applied to the nasal mucosa for use.

[0054] To further clarify the present invention and its technological advancements, the following description is provided in conjunction with specific embodiments and technical effects.

[0055] Example 1

[0056] This embodiment provides an astaxanthin composition for treating dry eye syndrome, comprising, by weight, 30 parts astaxanthin, 25 parts seaweed polysaccharide, 8 parts rhodioloside, 3 parts menthol, 2 parts borneol and 1 part lutein.

[0057] The preparation method of the astaxanthin composition in this embodiment is as follows:

[0058] S1: Astaxanthin, lecithin, and cholesterol were dissolved in ethanol, mixed thoroughly, and then the mixture was rotary evaporated in a rotary evaporator at 50 mbar and 40°C to remove the ethanol, yielding a uniform lipid film. The mass ratio of astaxanthin, lecithin, and cholesterol was 250:25:75.

[0059] Then, phosphate buffer was added to the lipid membrane, followed by sonication at a power of 150W for 8 minutes, with a 20-second pause after each 1-minute sonication interval, resulting in astaxanthin encapsulated in nanoliposomes. The volume-to-mass ratio of phosphate buffer to lipid membrane was 2.5 mL:1 g.

[0060] S2: Dissolve seaweed polysaccharide, rhodioloside, menthol, borneol and lutein in phosphate buffer to obtain a mixture.

[0061] S3: Astaxanthin encapsulated in nanoliposomes is mixed with the mixture to obtain a composition.

[0062] Example 2

[0063] This embodiment provides an astaxanthin composition for treating dry eye syndrome, comprising, by weight, 25 parts astaxanthin, 20 parts seaweed polysaccharide, 5 parts rhodioloside, 2 parts menthol, 1 part borneol and 0.5 parts lutein.

[0064] The preparation method of the astaxanthin composition in this embodiment is as follows:

[0065] S1: Astaxanthin, lecithin, and cholesterol were dissolved in ethanol, mixed thoroughly, and then the mixture was rotary evaporated in a rotary evaporator at 60 mbar and 42°C to remove the ethanol, yielding a uniform lipid film. The mass ratio of astaxanthin, lecithin, and cholesterol was 200:10:50.

[0066] Then, phosphate buffer was added to the lipid membrane, followed by sonication at a power of 200W for 6 minutes, with a 30-second pause after every 2 minutes, to obtain astaxanthin encapsulated in nanoliposomes. The volume-to-mass ratio of phosphate buffer to lipid membrane was 3 mL:1 g.

[0067] S2: Dissolve seaweed polysaccharide, rhodioloside, menthol, borneol and lutein in phosphate buffer to obtain a mixture.

[0068] S3: Astaxanthin encapsulated in nanoliposomes is mixed with the mixture to obtain a composition.

[0069] Example 3

[0070] This embodiment provides an astaxanthin composition for treating dry eye syndrome, comprising, by weight, 35 parts astaxanthin, 30 parts seaweed polysaccharide, 10 parts rhodioloside, 2.5 parts menthol, 1.2 parts borneol and 0.8 parts lutein.

[0071] The preparation method of the astaxanthin composition in this embodiment is as follows:

[0072] S1: Astaxanthin, lecithin, and cholesterol were dissolved in ethanol, mixed thoroughly, and then the mixture was rotary evaporated in a rotary evaporator at 40 mbar and 41°C to remove the ethanol, yielding a uniform lipid film. The mass ratio of astaxanthin, lecithin, and cholesterol was 300:20:100.

[0073] Then, phosphate buffer was added to the lipid membrane, followed by sonication at a power of 180W for 10 minutes, with a 20-second pause after each 1-minute sonication session. This yielded astaxanthin encapsulated in nanoliposomes. The volume-to-mass ratio of phosphate buffer to lipid membrane was 2 mL:1 g.

[0074] S2: Dissolve seaweed polysaccharide, rhodioloside, menthol, borneol and lutein in phosphate buffer to obtain a mixture.

[0075] S3: Astaxanthin encapsulated in nanoliposomes is mixed with the mixture to obtain a composition.

[0076] Example 4

[0077] This embodiment provides an astaxanthin composition for treating dry eye syndrome, comprising, by weight, 28 parts astaxanthin, 26 parts seaweed polysaccharide, 6 parts rhodioloside, 2 parts menthol, 1 part borneol and 0.6 parts lutein.

[0078] The preparation method of the astaxanthin composition in this embodiment is as follows:

[0079] S1: Astaxanthin, lecithin, and cholesterol were dissolved in ethanol, mixed thoroughly, and then the mixture was rotary evaporated in a rotary evaporator at 45 mbar and 41°C to remove the ethanol, yielding a uniform lipid film. The mass ratio of astaxanthin, lecithin, and cholesterol was 230:16:60.

[0080] Then, phosphate buffer was added to the lipid membrane, followed by sonication at a power of 160W for 7 minutes, with a 30-second pause after every 2 minutes, resulting in astaxanthin encapsulated in nanoliposomes. The volume-to-mass ratio of phosphate buffer to lipid membrane was 2.28 mL:1 g.

[0081] S2: Dissolve seaweed polysaccharide, rhodioloside, menthol, borneol and lutein in phosphate buffer to obtain a mixture.

[0082] S3: Astaxanthin encapsulated in nanoliposomes is mixed with the mixture to obtain a composition.

[0083] Comparative Example 1

[0084] This comparative example provides an astaxanthin composition for treating dry eye syndrome, which differs from Example 1 in that the astaxanthin content is 0.

[0085] Comparative Example 2

[0086] This comparative example provides an astaxanthin composition for treating dry eye syndrome, which differs from Example 1 in that the content of seaweed polysaccharide is 0.

[0087] Comparative Example 3

[0088] This comparative example provides an astaxanthin composition for treating dry eye syndrome, which differs from Example 1 in that the content of rhodioloside is 0.

[0089] Test 1:

[0090] 1. Animal preparation:

[0091] Several healthy 8-week-old BALB / c mice (excluding mice with corneal problems, abnormal fluorescence staining, and significant differences in tear secretion between the two eyes) were randomly divided into four groups: blank control group, negative control group, experimental group 1, experimental group 2, experimental group 3, experimental group 4, experimental group 5, experimental group 6, and experimental group 7. Each group contained 6 mice, and each group had 12 eyes. The corneal staining score was calculated using the average value of the number of eyes.

[0092] 2. Dry eye modeling and drug administration:

[0093] Mice in the blank control group were fed normally without any treatment.

[0094] Dry eye syndrome was induced by instilling 0.2% benzalkonium chloride solution into the eyes of mice in the negative control group and experimental groups 1-7 three times a day for 14 consecutive days.

[0095] Administration:

[0096] Blank control group: fed normally without any treatment.

[0097] Negative control group: Infused with physiological saline daily.

[0098] Experimental Groups 1-7: Each group was instilled with eye drops made from the compositions prepared in Examples 1-4 and Comparative Examples 1-3.

[0099] Dosage: 3 times a day for 14 consecutive days.

[0100] 3. Result Detection:

[0101] On day 15 after establishing the dry eye model, blank control mice and mice that had completed the model were stained with a 0.25% sodium fluorescein solution. Specifically, the 0.25% sodium fluorescein solution was left on the ocular surface of each group of mice for 10 seconds, and then excess stain was rinsed off with a 0.9% sodium chloride solution. The ocular surface was dried with cotton swabs, and the slit lamp light source was adjusted to cobalt blue light. The eyes of each group of mice were exposed under the slit lamp for observation. After adjusting the magnification, photos were taken, and the staining of the sodium fluorescein solution on the corneas of mice in different groups was recorded. The corneas of mice were divided into four quadrants: superior temporal, inferior temporal, superior nasal, and inferior nasal. Each quadrant was scored from 0 to 3 points, and each corneal score was the sum of the scores of the four quadrants. The scoring results are shown in Table 1. The corneal staining scores in Table 1 are the mean ± standard deviation. The scoring rules are as follows: no staining is 0 points; 1-30 punctate stains (mild) is 1 point; more than 30 punctate stains but the stains have not merged (moderate) is 2 points; corneal punctate stains that have merged, filamentous structures, and ulcers (severe) are 3 points.

[0102] Table 1. Statistical table of corneal staining scores in the blank group, negative control group, and each experimental group.

[0103]

[0104] A lower corneal score indicates a higher degree of corneal epithelial repair and better eye recovery in mice, while a higher score indicates more severe corneal damage.

[0105] Table 1 shows that the corneas of mice in the blank control group (which did not undergo modeling or drug administration) remained at a normal level throughout. The corneal epithelial staining area of ​​mice in the negative control group and experimental groups 1-7 increased significantly after modeling. Without additional drug administration, the corneal epithelial staining area of ​​mice in the negative control group further increased after 14 days. After 14 days of drug administration, the corneal epithelial staining area of ​​mice in experimental groups 1-4 returned to normal levels. The degree of corneal epithelial staining area repair was not significant in experimental groups 5-7, indicating that astaxanthin, seaweed polysaccharide, and rhodioloside have a synergistic effect, and the therapeutic effect is superior to that of any single or two effective components.

[0106] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An astaxanthin composition for treating dry eye syndrome, characterized in that, The product comprises, by weight, 30 parts astaxanthin, 25 parts seaweed polysaccharide, 8 parts rhodioloside, 3 parts menthol, 2 parts borneol, and 1 part lutein; the astaxanthin is encapsulated in nanoliposomes. The preparation method of the astaxanthin composition includes the following steps: S1: Astaxanthin, lecithin, and cholesterol are dissolved in an organic solvent, mixed thoroughly, and the organic solvent is removed to obtain a uniform lipid membrane. An aqueous solution is then added to the lipid membrane to hydrate it, followed by ultrasonic treatment to obtain astaxanthin encapsulated in nanoliposomes. The mass ratio of astaxanthin, lecithin, and cholesterol is 250:25:

75. The aqueous solution is a phosphate buffer solution, and the volume-to-mass ratio of the aqueous solution to the lipid membrane is 2.5 mL:1 g. The organic solvent is ethanol. The mixture of astaxanthin, lecithin, cholesterol, and the organic solvent is subjected to rotary evaporation at a reduced pressure of 40-60 mbar and a temperature of 40-42 °C to remove the organic solvent. The ultrasonic treatment power is 150-200W, the ultrasonic treatment time is 6-10min, and there is a 20-30s pause after every 1-2min of treatment; S2: Mix seaweed polysaccharide, rhodioloside, menthol, borneol and lutein to obtain a mixture; S3: Astaxanthin encapsulated in nanoliposomes is mixed with the mixture to obtain a composition; The astaxanthin composition is used to prepare eye patches, eye drops, eye ointments, or nasal mucosa ointments.

2. The use of the astaxanthin composition according to claim 1 in the preparation of eye patches.

3. The use of the astaxanthin composition according to claim 1 in the preparation of eye drops or eye ointment.

4. The use of the astaxanthin composition according to claim 1 in the preparation of nasal mucosal ointment.

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