KR102648372B1 - Zeaxanthin-loaded ferrocene nanoparticles having improved stability, and use thereof - Google Patents

Abstract

The present invention relates to zeaxanthin-loaded ferrocene nanoparticles with improved stability and a use thereof. More specifically, the present invention relates to zeaxanthin encapsulated with ferrocene nanoparticles and uses thereof, for example, in antioxidants, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions or food compositions.

Description

Zeaxanthin-loaded ferrocene nanoparticles having improved stability, and use thereof}

The present invention relates to zeaxanthin-loaded ferrocene nanoparticles with improved stability and uses thereof. More specifically, the present invention relates to zeaxanthin encapsulated in ferrocene nanoparticles and its use, for example as an antioxidant, in pharmaceutical compositions, quasi-drug compositions, cosmetic compositions or food compositions.

The exploration of the synthesis of nanoparticles and their applications has fascinated researchers around the world, and as such, nanotechnology has become a rapidly growing and innovative research field. Nanoparticles with sizes ranging from 1 to 100 nm show improved properties due to their large surface area and quantum effects. It can be applied to various fields such as materials science, environmental research, electronics, energy harvesting, manufacturing industry, machinery industry, textile industry, and food industry. Novel nanomaterials have received increasing attention in recent years due to their usefulness in fields of biology, engineering, agriculture and food safety.

Meanwhile, zeaxanthin is a high-value substance belonging to the Xanthophyll series of carotenoids and is one of about 600 natural carotenoids. Zeaxanthin is well known as an antioxidant, eye health supplement, and colorant used in raising livestock and fish, and is also known to have anti-inflammatory and anticancer effects. Zeaxanthin is a free-radical scavenger, and it has been confirmed that it has a very strong free-end oxygen removal ability (antioxidant effect) in biological tissues.

[constitutional formula]

Zeaxanthin is distributed in a concentrated form near the center of the macula in the human eye retina, and is known to absorb blue light from strong ultraviolet rays and protect the eyes from oxidative stress caused by free radical generation. Through this role, it is effective in preventing degenerative eye diseases caused by aging, such as cataracts and macular degeneration, which can cause deterioration of vision, and is also known to be distributed in the heart and skin. In addition, zeaxanthin is in the spotlight as a colorant for animal feed to prevent discoloration because it efficiently colors the fat, skin, and egg yolk of animals. Therefore, zeaxanthin can be used in various industries such as health supplements for eye health, cosmetics, and feed additives, and various products are being developed. However, when applying zeaxanthin to various products, there are limitations such as reduced efficacy and color change due to its unstable nature and color. Accordingly, the need to develop products and technologies that improve these problems is emerging.

Prior literature

1. Korean Open Patent KR 10-2023-0091552

As a result of the present inventors' diligent efforts to improve the stability and physicochemical properties of zeaxanthin, when zeaxanthin was encapsulated in ferrocene nanoparticles, not only did the storage stability improve without precipitation or color change of zeaxanthin, but the activity was also significantly improved. After confirming that it can exhibit oxygen removal activity, the present invention was completed.

However, the problem to be solved by the present application is not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

According to a first embodiment, the present invention

Ferrocene-containing polymer; and

Disclosed are zeaxanthin-loaded ferrocene nanoparticles with improved stability, which include zeaxanthin loaded inside the ferrocene-containing polymer.

According to one embodiment of the present invention, the zeaxanthin may be contained in an amount of 0.5 to 8% by weight, preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight, based on the weight of the ferroic acid polymer. there is.

In one embodiment of the present invention, the ferrocene-containing polymer is ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and polyethylene glycol methyl ether methacrylate (poly(ethylene glycol) ) methyl ether methacrylate, PEGMA) may be included in a molar ratio of 1:1~10:1~5.

According to a second embodiment, the present invention

Antioxidant containing zeaxanthin-loaded ferrocene nanoparticles with improved stability according to the first embodiment as an active ingredient, pharmaceutical composition for preventing, treating or improving diseases caused by excessive production of active oxygen, cosmetic composition and food The composition is disclosed.

According to one embodiment of the present invention, diseases caused by excessive production of active oxygen in the pharmaceutical composition include stroke, Parkinson's disease, Alzheimer's disease, aging, heart disease, eye disease, ischemia, arteriosclerosis, skin disease, and asthma. , inflammation, arthritis, autoimmune disease, hyperlipidemia, liver disease, diabetes, cancer, chronic ulcer, burn or wound.

According to one embodiment of the present invention, the quasi-drug composition may be a disinfectant cleaner, shower foam, garnish, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment, or filter filler.

According to one embodiment of the present invention, the symptoms or diseases caused by active oxygen in the cosmetic composition or food composition may be skin aging, wrinkle formation, skin pigmentation, atopy, acne, psoriasis, or eczema.

According to one embodiment of the present invention, the cosmetic may be manufactured in the form of an ampoule, cream, lotion, lotion, essence, or pack.

According to one embodiment of the present invention, the food includes meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, and drink preparations. , alcoholic beverages, or vitamin complexes.

Zeaxanthin encapsulated with ferrocene nanoparticles according to the present invention not only has significantly improved storage stability without precipitation or color change, but also has excellent free radical removal activity, is stable, and has excellent biocompatibility, so it is used as an antioxidant and pharmaceutical agent. It is expected that it can be effectively used in the development of compositions, quasi-drug compositions, cosmetic compositions, or food compositions.

Meanwhile, the scope of the present invention is not limited by the effects described above.

Figure 1 shows the results of evaluating the size and dispersion of zeaxanthin-ferrocene nanoparticles according to Example 1.
Figure 2 shows the storage stability evaluation results of zeaxanthin-ferrocene nanoparticles according to Example 1.
Figure 3 shows the results of evaluating the DPPH radical scavenging ability of ZX@FNP2 according to Example 2.
Figure 4 shows the results of evaluating the ability of ZX@FNP2 to inhibit ROS generation according to Example 3.
Figure 5 shows the size and dispersion evaluation results of ZX@FNP2 according to Example 4.
Figure 6 shows the storage stability evaluation results of ZX@FNP2 according to Example 4.
Figure 7 shows the color stability evaluation results of ZX@FNP2 according to Example 4.

Hereinafter, zeaxanthin-loaded ferrocene nanoparticles with improved stability according to specific embodiments of the invention and their uses will be described in detail. However, this is presented as an example of the invention, and the scope of the invention is not limited thereby, and it is obvious to those skilled in the art that various modifications to the embodiment are possible within the scope of the invention. Throughout this specification, unless otherwise specified, “include” or “contains” refers to the inclusion of a certain component (or component) without particular limitation, excluding the addition of other components (or components). cannot be interpreted as

The term "antioxidant" used in this specification refers to the action of suppressing oxidation. The human body has a balance of prooxidants and antioxidants, but this balance is affected by various factors. If it becomes unbalanced and leans toward pro-oxidation, oxidative stress is induced, causing potential cell damage and pathological diseases. Reactive oxygen species (ROS), which are the direct cause of this oxidative stress, are unstable and highly reactive, easily reacting with various biological substances, and attacking macromolecules in the body, causing irreversible damage to cells and tissues, mutations, and mutations. It causes cytotoxicity and carcinogenesis. Reactive nitrogen species (RNS) such as NO, HNO ₂ ^and ONOO - are produced in large quantities due to the immune response of macrophages, neutrophils and other immune cells during inflammatory reactions, and ROS is also produced at this time. The above-described free radicals oxidize and destroy cells in the body, thereby exposing them to various diseases.

As used herein, the term "treatment" refers to an individual suffering from a disease or at risk of developing a disease, improving the condition of the individual, delaying the progression of the disease, delaying the onset of symptoms, or slowing the progression of symptoms, etc. It means any form of treatment or prevention that provides effects including. Accordingly, the term “treatment” includes prophylactic treatment of an individual, preventing the occurrence of symptoms. Additionally, the terms “treatment” and “prevention” are not intended to imply cure or complete elimination of symptoms.

As used herein, the term “improvement” may refer to any action that at least reduces the severity of a parameter, such as a symptom, associated with the alleviation or treatment of a condition.

1. Zeaxanthin-loaded ferrocene nanoparticles with improved stability

This invention

Ferrocene-containing polymer; and

The object of the present invention is to provide zeaxanthin-loaded ferrocene nanoparticles with improved stability, which include zeaxanthin loaded inside the ferrocene-containing polymer.

In the zeaxanthin-loaded ferrocene nanoparticles with improved stability according to the present invention, the zeaxanthin is present in an amount of 0.5 to 8% by weight, preferably 0.5 to 4% by weight, more preferably 1 to 4% by weight, based on the weight of the ferroic acid polymer. It may be contained in an amount of weight percent.

In the zeaxanthin-loaded ferrocene nanoparticles with improved stability according to the present invention, the ferrocene-containing polymer is ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and polyethylene glycol methyl ether. Methacrylate (poly(ethylene glycol) methyl ether methacrylate, PEGMA) may be included in a molar ratio of 1:1~10:1~5.

In the zeaxanthin-loaded ferrocene nanoparticles with improved stability according to the present invention, the size of the nanoparticles may be 10 to 300 nm, preferably 20 to 200 nm.

2. Use of zeaxanthin-loaded ferrocene nanoparticles with improved stability

The present invention seeks to provide the use of zeaxanthin-loaded ferrocene nanoparticles with improved stability in antioxidants, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, or food compositions.

(1) Antioxidants

The present invention seeks to provide an antioxidant containing zeaxanthin-loaded ferrocene nanoparticles with improved stability as an active ingredient.

In the antioxidant according to the present invention, the zeaxanthin may be contained in an amount of 0.5 to 8% by weight, preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight, based on the weight of the ferroic acid polymer. there is.

In the antioxidant according to the present invention, the ferrocene-containing polymer is ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and polyethylene glycol methyl ether methacrylate (poly(ethylene glycol) ) methyl ether methacrylate, PEGMA) may be included in a molar ratio of 1:1~10:1~5.

In the antioxidant according to the present invention, the size of the nanoparticles may be 10 to 300 nm, preferably 20 to 200 nm.

(2) Pharmaceutical composition

The present invention seeks to provide a pharmaceutical composition for the prevention or treatment of diseases caused by excessive production of active oxygen containing zeaxanthin-loaded ferrocene nanoparticles with improved stability as an active ingredient.

In the pharmaceutical composition according to the present invention, the zeaxanthin may be contained in an amount of 0.5 to 8% by weight, preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight, based on the weight of the ferroic acid polymer. You can.

In the pharmaceutical composition according to the present invention, the ferrocene-containing polymer is ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and polyethylene glycol methyl ether methacrylate (poly(ethylene) glycol) methyl ether methacrylate (PEGMA) may be included in a molar ratio of 1:1~10:1~5.

In the pharmaceutical composition according to the present invention, the nanoparticles may have a size of 10 to 300 nm, preferably 20 to 200 nm.

In the pharmaceutical composition according to the present invention, diseases caused by excessive production of active oxygen include stroke, Parkinson's disease, Alzheimer's disease, aging, heart disease, eye disease, ischemia, arteriosclerosis, skin disease, asthma, inflammation, and arthritis. , autoimmune disease, hyperlipidemia, liver disease, eye disease, diabetes, cancer, chronic ulcer, burn or wound. For example, the eye diseases include macular degeneration (e.g., macular degeneration due to aging), vision loss, cataracts, glaucoma, ocular peroxidation, retinal damage, dry eye, diabetic retinopathy, non-exudative age-related macular degeneration, and exudative Macular degeneration including age-related macular degeneration, choroidal neovascularization, retinopathy, acute and chronic macular neuroretinopathy, central serous chorioretinopathy, macular edema, acute multifocal lamellar pigment epitheliosis, birdshot retinochoroidopathy, posterior scleritis, Tortuous choroiditis, subretinal fibrosis, uveitis syndrome, retinal artery occlusion disease, central retinal vein occlusion, disseminated intravascular coagulation, branch retinal vein occlusion, hypertensive fundus changes, ocular ischemic syndrome, retinal artery microaneurysm, Coates Disease, foveal telangiectasia, hemiretinal vein occlusion, papillary phlebitis, central retinal artery occlusion, branch retinal artery occlusion, branchial angiitis, sickle cell retinopathy, vascular pattern retinopathy, familial exudative vitreoretinopathy, Eels disease, Proliferative vitreoretinopathy, proliferative diabetic retinopathy, tumor-related retinal diseases, congenital thickening of the retinal pigment epithelium (RPE), posterior uveal melanoma, choroidal hemangioma, choroidal osteoma, choroidal metastases, complex hamartoma of the retina and retinal pigment epithelium, It may be selected from the group consisting of retinoblastoma, angioproliferative tumor of the fundus, retinal astrocytoma, intraocular lymphoid tumor, myopic retinal degeneration and acute retinal pigment epitheliitis and glaucoma. The arthritis may be selected from the group consisting of osteoarthritis, degenerative arthritis, rheumatoid arthritis, osteochondritis dissecans, joint ligament damage, meniscus damage, joint malalignment, avascular necrosis, and juvenile idiopathic arthritis.

The pharmaceutical composition according to the present invention can be administered to patients by general oral or parenteral administration methods, and can be in any form, solid or liquid. Additionally, the pharmaceutical composition according to the present invention may further include one or more pharmaceutically acceptable liquid or solid carriers. Additionally, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. The solid preparation may include tablets, pills, powders, granules, capsules, pellets, fine granules or powders, and such solid preparations can be prepared by adding a carrier, excipient and/or diluent to the complex. The carrier, excipients and/or diluents include lactose, sucrose, dextrose, mannitol, malitol, sorbitol, xylitol, and erythritol. (erithritol), starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, polyvinyl pyrrolidone (polyvinyl pyrrolidone), magnesium stearate, and mineral oil. The liquid formulation may be a solution, suspension, or emulsion, and may contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives in addition to commonly used simple diluents such as water and liquid paraffin. Aqueous suspensions suitable for oral use may be prepared by dispersing the finely divided active ingredient in viscous substances such as natural or synthetic gums, resins, methyl cellulose, sodium carboxymethyl cellulose and known suspending agents. You can. Parenteral administration agents include injections, drops, fluids, ointments, sprays, suspensions, emulsions, and suppositories. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, cacao, laurin, glycerogelatin, etc. can be used.

(3) Quasi-drug composition

The present invention seeks to provide a quasi-drug composition for preventing or treating diseases caused by excessive production of active oxygen containing zeaxanthin-loaded ferrocene nanoparticles with improved stability as an active ingredient.

In the quasi-drug composition according to the present invention, the zeaxanthin may be contained in an amount of 0.5 to 8% by weight, preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight, based on the weight of the ferroic acid polymer. there is.

In the quasi-drug composition according to the present invention, the ferrocene-containing polymer is ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and polyethylene glycol methyl ether methacrylate (poly(ethylene glycol) ) methyl ether methacrylate, PEGMA) may be included in a molar ratio of 1:1~10:1~5.

In the quasi-drug composition according to the present invention, the size of the nanoparticles may be 10 to 300 nm, preferably 20 to 200 nm.

In the quasi-drug composition according to the present invention, the quasi-drug composition is characterized in that it is a disinfectant cleaner, shower foam, gagreen, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment, or filter filler.

(4) Cosmetic composition

The present invention seeks to provide a cosmetic composition for preventing or improving symptoms or diseases caused by excessive production of active oxygen containing zeaxanthin-loaded ferrocene nanoparticles with improved stability as an active ingredient.

In the cosmetic composition according to the present invention, the symptoms or diseases caused by the active oxygen are skin aging, wrinkle formation, skin pigmentation, atopy, acne, psoriasis or eczema.

In the cosmetic composition according to the present invention, the zeaxanthin may be contained in an amount of 0.5 to 8% by weight, preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight, based on the weight of the ferroic acid polymer. there is.

In the cosmetic composition according to the present invention, the ferrocene-containing polymer is ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and polyethylene glycol methyl ether methacrylate (poly(ethylene glycol) ) methyl ether methacrylate, PEGMA) may be included in a molar ratio of 1:1~10:1~5.

In the cosmetic composition according to the present invention, the size of the ursodeoxycholic acid nanoparticle complex may be 10 to 300 nm, preferably 20 to 200 nm.

In the cosmetic composition according to the present invention, the cosmetic may be manufactured in the form of an ampoule, cream, lotion, lotion, essence, or pack. Additionally, in order to facilitate storage and handling, carriers commonly used in formulations such as dextrin and cyclodextrin, and other arbitrary auxiliaries may be added.

(5) Food composition

The present invention seeks to provide a food composition for preventing or improving symptoms or diseases caused by free radicals containing zeaxanthin-loaded ferrocene nanoparticles with improved stability as an active ingredient.

In the food composition according to the present invention, the symptoms or diseases caused by the active oxygen are characterized by skin aging, wrinkle formation, skin pigmentation, atopy, acne, psoriasis or eczema.

In the food composition according to the present invention, the zeaxanthin may be contained in an amount of 0.5 to 8% by weight, preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight, based on the weight of the ferroic acid polymer. there is.

In the food composition according to the present invention, the ferrocene-containing polymer is ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and polyethylene glycol methyl ether methacrylate (poly(ethylene glycol) ) methyl ether methacrylate, PEGMA) may be included in a molar ratio of 1:1~10:1~5.

In the food composition according to the present invention, the size of the nanoparticles may be 10 to 300 nm, preferably 20 to 200 nm.

In the food composition according to the present invention, the food includes meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, and drink preparations. , characterized in that it is an alcoholic beverage or a vitamin complex.

In the food composition according to the present invention, the food composition contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, It may contain preservatives, glycerin, alcohol, carbonating agents used in carbonated drinks, etc. Additionally, the composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients can be used independently or in combination.

Hereinafter, various embodiments are presented to aid understanding of the invention. The following examples are provided to make the invention easier to understand, and the scope of protection of the invention is not limited to the following examples.

<Example>

Example 1. Preparation and characterization of zeaxanthin-ferrocene nanoparticles

1.1 Preparation of ferrocene polymer

Three types of monomers are used: ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA). Poly(FMMA- r -PEGMA- r -MA) polymer was prepared. First, FMMA (0.4 mmol) was added to MA and PEGMA according to the molar ratio shown in Table 1, then azovisisobutyronitrile (AIBN) was added and dissolved in 2 ml tetrahydrofuran (THF), and incubated at 70°C for 24 hours. The polymer was prepared by polymerization using magnetic stirring for a period of time.

polymer FMMA M.A. PEG Poly-PC-1 0.4 2 0 Poly-PC-2 0.4 1.5 0.5 Poly-PC-3 0.4 0 2

1.2 Preparation of zeaxanthin-loaded ferrocene nanoparticles

The prepared mixed solution containing ferrocene polymer, zeaxanthin, and ethanol (1 mL) was placed in a 4 mL vial, and the mixed solution was stabilized in a shaking rottery for 2 hours. The amount of zeaxanthin was added at 4% by weight (0.2mg) based on the weight of the ferrocene polymer. Next, 5ml of DI.Water was filled into a 20ml vial containing a magnetic bar, and then the mixed solution was added dropwise for 10 minutes at a speed of 530rpm. After dropwise, close the vial cap and stir for 60 minutes to stabilize the nanoparticles. After placing them in the dessicator, remove ethanol using a cold trap (fixation conditions: -40 degrees, time: 2h) to form zeaxanthin-containing ferrocene nanocapsules. got it At this time, zeaxanthin-loaded ferrocene nanoparticles (ZX@FNP) prepared using the above-prepared polymers Poly-PC-1, Poly-PC-2, and Poly-PC-3 were ZX, respectively. They were named @FNP1, ZX@FNP2, and ZX@FNP3.

1.3 Characteristic evaluation

To confirm the stability of the zeaxanthin-loaded ferrocene nanocapsules, size and PDI were measured. As a result, the size and dispersion of ZX@FNP2 and ZX@FNP3 were both found to be about 158 nm and less than 0.3 (Figure 1), and the size and dispersion remained constant even up to about 21 days after preparation, especially ZX@ In the case of FNP2, it was confirmed that it remained stable even after about 28 days after manufacturing (Figure 2).

Example 2. Evaluation of DPPH radical scavenging ability of ZX@FNP2

Confirmation of DPPH radical scavenging activity DPPH radical scavenging activity was used to measure antioxidant activity, and DPPH radical scavenging activity was measured by modifying the method of Blois (1958). 100ul of 0.2mM DPPH (2,2-diphenyl-1-picrylhydrazyl, Sigma) solution was dispensed into 100ul of each sample, left for 30 minutes, and the absorbance was measured at 520 nm using an ELISA reader (Thermo). The control group was measured in the same way by adding a solvent instead of the sample. In addition, in order to correct the absorbance value for the color of the sample itself, ethanol was added instead of 0.2 mM DPPH, the absorbance was measured, and the DPPH radical scavenging ability was calculated using the following equation 1:

[Equation 1]

DPPH radical scavenging ability = (1-absorbance of sample added/absorbance of no sample added)×100

As a result, it was confirmed that the DPPH radical scavenging activity of zeaxanthin itself was about 45%, while ZX@FNP2 showed an activity of about 60%, showing comparable results to the DMSO lysate (Figure 3).

Example 3. Evaluation of the ability of ZX@FNP2 to inhibit ROS generation

The cell line used in the test was the human keratinocytes HaCaT cell line, which was distributed at 8.0x103 per well in a 96-well black plate for fluorescence measurement and added to DMEM (Dulbeccos Modification of Eagles Medium) containing penicillin/streptomycin. , FBS 10%) medium was used, and the test samples were treated after culturing for 1 day at 37°C and 5% CO2 conditions. Serum-free DMEM (FBS free) was used as the medium used and cultured for 1 day at 37°C and 5% CO2 conditions. After adding the sample and culturing it for 24 hours, the remaining medium was removed by washing with HBSS (Hanks' Balanced Salt solution), and 100 μl of DCFH-DA (2',7'-Dichlorofluorescein diacetate, Sigma) prepared at 50 μM in HBSS was added. It was incubated for 1 hour at 37°C under 5% CO2 conditions and washed with HBSS. Afterwards, 100 μl of HBSS was treated with UVB 20 mJ/cm2. After 30 minutes of UV treatment, the fluorescence intensity of DCF (dichlorofluorescein) oxidized to ROS was measured using a fluorescence plate reader (Ex = 485 nm, Em = 530 nm). Measured values were calculated as % Control based on UV control.

As a result, ROS increased by about 50% through UV treatment, and ROS production was reduced by about 47% when treated with Trolox, a positive control group. When treated with ZX extract_D.W (ZX 1ppm), ROS generation was reduced by 15%, and when treated with ZX extract_DMSO (ZX 1ppm), it decreased by 28%, while when treated with ZX@FNP2 (1 ppm), it decreased by about 51%, indicating that ZX@FNP2 It was confirmed that the ROS scavenging ability was superior to that of DMSO lysate (Figure 4).

Example 4. Preparation and characterization of ZX@FNP2 according to the loading amount of zeaxanthin

4.1 Preparation of ZX@FNP2

A mixed solution containing 5 mg of the ferrocene polymer Poly-PC-2 prepared in the above example, zeaxanthin, and ethanol (1 mL) was placed in a 4 mL vial, and the mixed solution was stabilized in a shaking rottery for 2 hours. At this time, the amount of zeaxanthin varies in amounts of 1% by weight (0.05mg), 2% by weight (0.1mg), 4% by weight (0.2mg), and 8% by weight (0.4mg) based on the weight of the ferrocene polymer. Added. Next, 5ml of DI.Water was filled into a 20ml vial containing a magnetic bar, and then the mixed solution was added dropwise for 10 minutes at a speed of 530rpm. After dropwise, close the vial cap and stir for 60 minutes to stabilize the nanoparticles. After placing them in the dessicator, remove ethanol using a cold trap (fixation conditions: -40 degrees, time: 2h) to form zeaxanthin-containing ferrocene nanocapsules. got it

4.2 Characteristic evaluation

To confirm the stability of ZX@FNP2, size, PDI, and color were measured. As a result, when zeaxanthin was loaded in an amount of 0.5 to 4% by weight based on the weight of the ferrocene polymer, the size and dispersion were found to be less than about 150 nm and less than 0.2, respectively (FIG. 5), and about 14 days after production. The size and dispersion remained constant, and in particular, when zeaxanthin was loaded at 4% by weight based on the weight of the ferrocene polymer, it was confirmed that it remained stable even after about 28 days after production (FIG. 6). Meanwhile, in the case of color, it was confirmed that the color remained stable without any color change, except for a slight increase in turbidity when zeaxanthin was loaded at 8% by weight based on the weight of the ferrocene polymer even up to about 28 days after manufacture (Figure 7) .
This invention is a technology developed through a national research and development project under project number BT220140:
Task identification number: 220140
Task number: BT220140
Name of Ministry: Seoul Metropolitan Government
Name of project management (professional) organization: Seoul Business Agency
Research Project Name: 2022 Biomedical Technology Commercialization Support Project
Research project name: Development of new functional cosmetic material for ferrocene nanocapsules containing tetraterpenoids derived from microorganisms
Name of project carrying out organization: Ravio Co., Ltd.
Research period: 2022.09.01 ~ 2024.08.31

As the specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred implementation examples and do not limit the scope of the present invention. Accordingly, the practical scope of the present invention will be defined by the appended claims and their equivalents.

Claims (14)

Ferrocene-containing polymer; and
Zeaxanthin-loaded ferrocene nanoparticles with improved stability, comprising zeaxanthin loaded inside the ferrocene-containing polymer,
The ferrocene-containing polymer includes ferrocenylmethyl methacrylate (FMMA), methacrylic acid (MA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA). : 1~10 : Contained in a molar ratio of 1~5,
Zeaxanthin-loaded ferrocene nanoparticles with improved stability, characterized in that the zeaxanthin is contained in an amount of 0.5 to 4% by weight based on the weight of the ferrocene-containing polymer.
delete delete delete A pharmaceutical composition for preventing or treating diseases caused by excessive production of active oxygen comprising the zeaxanthin-loaded ferrocene nanoparticles with improved stability according to claim 1 as an active ingredient,
Diseases caused by excessive production of active oxygen are characterized by stroke, Parkinson's disease, Alzheimer's disease, aging, ischemia, arteriosclerosis, asthma, inflammation, arthritis, hyperlipidemia, diabetes, cancer, chronic ulcers, burns or wounds. Phosphorus, pharmaceutical composition.
delete A quasi-drug composition for preventing or improving diseases caused by excessive production of active oxygen containing the zeaxanthin-loaded ferrocene nanoparticles with improved stability according to claim 1 as an active ingredient,
Diseases caused by excessive production of active oxygen are stroke, Parkinson's disease, Alzheimer's disease, aging, ischemia, arteriosclerosis, asthma, inflammation, arthritis, hyperlipidemia, diabetes, cancer, chronic ulcers, burns or wounds. Phosphorus, quasi-drug composition.
In clause 7,
The quasi-drug composition is characterized in that it is a disinfectant cleaner, shower foam, garnish, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment, or filter filler.
A cosmetic composition for preventing or improving symptoms or diseases caused by excessive production of active oxygen comprising the zeaxanthin-loaded ferrocene nanoparticles with improved stability according to claim 1 as an active ingredient,
A cosmetic composition, wherein the symptom or disease caused by the active oxygen is skin aging or wrinkle formation.
delete According to clause 9,
A cosmetic composition, characterized in that the cosmetic is manufactured in the form of an ampoule, cream, lotion, lotion, essence, or pack.
A food composition for preventing or improving symptoms or diseases caused by active oxygen, comprising the zeaxanthin-loaded ferrocene nanoparticles with improved stability according to claim 1 as an active ingredient,
A food composition, wherein the symptom or disease caused by the active oxygen is skin aging or wrinkle formation.
delete According to clause 12,
A food composition, wherein the food is sausage, bread, chocolate, confectionery, pizza, ramen, beverage, tea, drink, or vitamin complex.