KR102251184B1 - Prussian blue/chitosan nanoparticle complexes for removing reactive oxygen species and its uses - Google Patents

Prussian blue/chitosan nanoparticle complexes for removing reactive oxygen species and its uses Download PDF

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KR102251184B1
KR102251184B1 KR1020190022487A KR20190022487A KR102251184B1 KR 102251184 B1 KR102251184 B1 KR 102251184B1 KR 1020190022487 A KR1020190022487 A KR 1020190022487A KR 20190022487 A KR20190022487 A KR 20190022487A KR 102251184 B1 KR102251184 B1 KR 102251184B1
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chitosan
prussian blue
disease
molecular weight
nanoparticle complex
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최원일
오혜련
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한국세라믹기술원
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Abstract

본 발명은 활성산소 제거를 위한 프러시안 블루/키토산 나노입자 복합체 및 이의 용도에 관한 것이다. 본 발명에 따른 프러시안 블루/키토산 나노입자 복합체는 활성산소제거 능력 및 항균성이 뛰어나고 안정적이며 생체적합성이 우수하므로, 항산화제, 약제학적 조성물, 의약외품 조성물, 화장료 조성물 또는 식품 조성물의 개발에 효과적으로 사용될 수 있다. The present invention relates to a Prussian blue/chitosan nanoparticle complex and its use for the removal of active oxygen. The Prussian blue/chitosan nanoparticle complex according to the present invention has excellent active oxygen removal ability and antibacterial properties, is stable, and has excellent biocompatibility, so it can be effectively used in the development of antioxidants, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, or food compositions. have.

Description

활성산소 제거를 위한 프러시안 블루/키토산 나노입자 복합체 및 이의 용도{Prussian blue/chitosan nanoparticle complexes for removing reactive oxygen species and its uses}Prussian blue/chitosan nanoparticle complexes for removing reactive oxygen species and its uses}

본 발명은 활성산소 제거를 위한 프러시안 블루/키토산 나노입자 복합체 및 이의 용도에 관한 것이다. 본 발명에 따른 프러시안 블루/키토산 나노입자 복합체는 활성산소제거 능력 및 항균성이 뛰어나고 안정적이며 생체적합성이 우수하므로, 항산화제, 약제학적 조성물, 의약외품 조성물, 화장료 조성물 또는 식품 조성물의 개발에 효과적으로 사용될 수 있다. The present invention relates to a Prussian blue/chitosan nanoparticle complex and its use for the removal of active oxygen. The Prussian blue/chitosan nanoparticle complex according to the present invention has excellent active oxygen removal ability and antibacterial properties, is stable, and has excellent biocompatibility, so it can be effectively used in the development of antioxidants, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, or food compositions. have.

자연계에 존재하는 활성 산소(자유 라디칼, free radicals)는 짝지어지지 않은 전자를 가지는 물질의 형태로 존재하여 주변 화합물과 빠르게 반응하는 물질이다. 인체에서 발생하는 활성산소는 산화/환원 작용과 물질의 대사 작용의 결과로 생성되는 것으로 알려져 있다(1993, Drugs and Aging, 3, 60-80). 또한, 식품에서 발생된 활성산소는 산화 작용을 유발하여 품질을 저하시키고 이를 섭취하면 인체 내에서 각종 질병을 유발한다(2008, Carbohydrate polymers, 74, 953-956). 식품에서 활성산소의 발생은 주로 식품 내에 존재하는 불포화 지방과 연쇄 반응하여 산패를 유발하여 식품의 풍미(Flavor)를 저하시켜 식품의 가치를 하락시키며 일단 활성 산소로 인한 산화 작용이 일어나면 지속적으로 불포화 지방산을 산화시켜 연쇄반응을 유발해서 산화에 의한 산패를 지속시킨다. 천연 식품에 존재하는 비타민 C와 E, 그리고 다양한 페놀 화합물과 같은 항산화 물질들은 식품에 존재하는 활성산소의 억제를 유발한다(2009, Food Chemistry, 114, 881-888). 이러한 활성산소 제거기능을 하는 물질들의 섭취는 체내에서 노화나 소화 혹은 대사를 통해 생산되는 활성산소를 제거하는 기능을 한다. Active oxygen (free radicals) existing in nature exists in the form of a substance with unpaired electrons, and is a substance that reacts quickly with surrounding compounds. It is known that free radicals occurring in the human body are produced as a result of oxidation/reduction and metabolism of substances (1993, Drugs and Aging, 3, 60-80). In addition, free radicals generated from food cause oxidation to degrade quality, and when ingested, it causes various diseases in the human body (2008, Carbohydrate polymers, 74, 953-956). The generation of free radicals in food mainly causes rancidity by chain reaction with unsaturated fats present in the food, reducing the flavor of the food, thereby reducing the value of the food.Once the oxidation of free radicals occurs, unsaturated fatty acids continue to occur. It oxidizes and induces a chain reaction to sustain rancidity due to oxidation. Antioxidants such as vitamins C and E and various phenolic compounds in natural foods cause inhibition of free radicals in food (2009, Food Chemistry, 114, 881-888). Ingestion of these substances that remove active oxygen functions to remove active oxygen produced through aging, digestion or metabolism in the body.

인체 내에서 각종 대사와 노화를 통해 발생하는 활성산소(자유 라디칼, free radicals)는 체내에 존재하는 활성산소제거효소에 의해 보통 균형을 이루고 있지만 미세먼지나 자외선 등의 외부요인 및 종양이나 염증, 심혈관 질환 등의 내부요인에 의해 비이상적으로 증가한다. 이 과잉생성된 활성산소는 단백질(Proteins), 지방(lipids)과 반응하여 노화(Aging)를 촉진시키고(2002, Archives of Biochemistry and Biophysics, 379, 354-9), 빈혈, 당뇨 또는 혈관 수축성 심장질환 같은 만성질환을 유발한다.(2007, Biochemistry(Moscow), 2, 809-827) 또한 활성산소(프리 라디칼, free radicals)는 핵산(Nucleic acid)이나 염색체(Chromosome)의 산화를 유발하여 생명에 치명적인 각종 암을 발생시키는 주요 요인 중의 하나로 알려져 있다.(2003, Biol.Pharm. Bull. 26, 1129-1134). 이러한 이유로 체내에서 과잉 발생하는 활성산소의 제거는 노화를 비롯한 각종 만성 질병과 생명에 치명적인 암의 예방의 필수 불가결한 것이다. Free radicals (free radicals) generated through various metabolism and aging in the human body are usually balanced by active oxygen scavenging enzymes present in the body, but external factors such as fine dust or ultraviolet rays, tumors, inflammation, cardiovascular system It increases abnormally due to internal factors such as disease. This overproduced free radical reacts with proteins and lipids to promote aging (2002, Archives of Biochemistry and Biophysics, 379, 354-9), and anemia, diabetes, or vasoconstrictive heart disease. (2007, Biochemistry (Moscow), 2, 809-827) In addition, free radicals (free radicals) cause oxidation of nucleic acids or chromosomes, which is fatal to life. It is known as one of the major factors causing various cancers (2003, Biol. Pharma. Bull. 26, 1129-1134). For this reason, the removal of excess free radicals in the body is indispensable for the prevention of various chronic diseases including aging and life-threatening cancer.

효과적으로 활성산소들을 제거할 수 있는 물질들은 이미 많이 개발되어 왔다. 대표적인 예로는 항산화제인 비타민계열 (retinol, tocophenol 등), 금나노입자, 플래티넘, 바나듐, 산화세륨 나노입자들이 있다. 최근에는 프러시안 블루 나노입자 (Prussian blue nanoparticle)들이 항산화 효소 (peroxidase (POD), catalase (CAT), superoxide dismutase (SOD) 등)의 기능을 보여줌으로써 활성산소들을 효과적으로 제거하고 생체 내에서 안전하게 항산화 효능을 보여줄 수 있는 가능성이 제기됐다.Materials that can effectively remove free radicals have already been developed. Representative examples include antioxidant vitamins (retinol, tocophenol, etc.), gold nanoparticles, platinum, vanadium, and cerium oxide nanoparticles. In recent years, Prussian blue nanoparticles have shown the functions of antioxidant enzymes (peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), etc.), effectively removing active oxygen and safe antioxidant efficacy in vivo. The possibility to show was raised.

프러시안 블루 나노 입자들은 미국 식약처 (US FDA)의 승인을 받은 물질로 방사능 물질들을 제거할 수 있는 기능을 가지고 있으며 세포 독성이 전혀 없는 생체 내 안전성이 높은 물질이다. 또한 근적외선(NIR) 파장에서 강한 흡광도를 보임으로써 암 치료를 위한 photothermal ablation agent와 photoacoustic imaging contrast agent, MRI 조영제로 조명되고 있다. 하지만 프러시안 블루 나노입자 자체는 생체 내 안정성이 낮아 쉽게 뭉침 현상(aggregation)이 발생할 수 있어서, 유기물질들을(polyvinylpyrrolidone (PVP), polylactic acid(PLA), polydiallyldimethylammonium chloride(PDDA) 등) template로 첨가해 구조적인 안정성을 향상시키는 연구들이 많이 진행되고 있다. Prussian blue nanoparticles have been approved by the US Food and Drug Administration (US FDA), have the ability to remove radioactive substances, and are highly safe in vivo with no cytotoxicity. In addition, by showing strong absorbance at the near-infrared (NIR) wavelength, it is being illuminated as a photothermal ablation agent, photoacoustic imaging contrast agent, and MRI contrast agent for cancer treatment. However, Prussian blue nanoparticles themselves have low stability in vivo and can easily cause aggregation, so organic substances (polyvinylpyrrolidone (PVP), polylactic acid (PLA), polydiallyldimethylammonium chloride (PDDA), etc.) are added as a template. There are many studies on improving structural stability.

이에 본 발명자들은 프러시안 블루 나노 입자들의 안정성을 향상시킬 수 있을 뿐 아니라 항산화 효능을 증가시킬 수 있는 키토산을 template로 사용하여 프러시안 블루/키토산 나노입자(Prussian blue/chitosan nanoparticle, PB/Chi NP) 복합체를 제조하고, 이의 활성산소 제거 효과를 확인함으로써 본 발명을 완성하였다. 본 발명에 따른 프러시안 블루/키토산 나노입자 복합체의 제조 방법에 대한 모식도를 도 1에 나타내었다. Accordingly, the present inventors use chitosan, which can not only improve the stability of Prussian blue nanoparticles, but also increase antioxidant efficacy, as a template, and use Prussian blue/chitosan nanoparticles (PB/Chi NP). The present invention was completed by preparing a composite and confirming its effect of removing active oxygen. A schematic diagram of a method for preparing a Prussian blue/chitosan nanoparticle composite according to the present invention is shown in FIG. 1.

본 발명은 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 항산화제를 제공하는 것을 목적으로 한다. An object of the present invention is to provide an antioxidant comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명은 또한 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 약제학적 조성물을 제공하는 것을 목적으로 한다. Another object of the present invention is to provide a pharmaceutical composition comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명은 또한 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 의약외품 조성물을 제공하는 것을 목적으로 한다. Another object of the present invention is to provide a quasi-drug composition comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명은 또한 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 화장료 조성물을 제공하는 것을 목적으로 한다. Another object of the present invention is to provide a cosmetic composition comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명은 또한 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 식품 조성물을 제공하는 것을 목적으로 한다. Another object of the present invention is to provide a food composition comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

제1구현예에 따르면, According to the first embodiment,

본 발명은 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 항산화제를 제공하고자 한다. The present invention is to provide an antioxidant comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명에 따른 항산화제에 있어서, 상기 키토산 나노입자의 분자량은 1 내지 50kDa인 것을 특징으로 한다. In the antioxidant according to the present invention, the chitosan nanoparticles have a molecular weight of 1 to 50 kDa.

본 발명에 따른 항산화제에 있어서, 상기 키토산 나노입자의 분자량은 10kDa인 것을 특징으로 한다. In the antioxidant according to the present invention, the chitosan nanoparticles have a molecular weight of 10 kDa.

본 발명에 따른 항산화제에 있어서, 상기 프러시안 블루/키토산 나노입자 복합체의 크기는 1 내지 500 nm인 것을 특징으로 한다. In the antioxidant according to the present invention, the Prussian blue/chitosan nanoparticle complex has a size of 1 to 500 nm.

제2구현예에 따르면,According to the second embodiment,

본 발명은 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 활성산소 과잉생성으로 인해 유발되는 질환의 예방 또는 치료용 약제학적 조성물을 제공하고자 한다. An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of diseases caused by overproduction of active oxygen, comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명에 따른 약제학적 조성물에 있어서, 상기 키토산 나노입자의 분자량은 1 내지 50kDa인 것을 특징으로 한다. In the pharmaceutical composition according to the present invention, the chitosan nanoparticles have a molecular weight of 1 to 50 kDa.

본 발명에 따른 약제학적 조성물에 있어서, 상기 키토산 나노입자의 분자량은 10kDa인 것을 특징으로 한다. In the pharmaceutical composition according to the present invention, the chitosan nanoparticles have a molecular weight of 10 kDa.

본 발명에 따른 약제학적 조성물에 있어서, 상기 프러시안 블루/키토산 나노입자 복합체의 크기는 1 내지 500 nm인 것을 특징으로 한다. In the pharmaceutical composition according to the present invention, the Prussian blue/chitosan nanoparticle complex has a size of 1 to 500 nm.

본 발명에 따른 약제학적 조성물에 있어서, 상기 활성산소 과잉생성으로 인해 유발되는 질환은 뇌졸중, 파킨슨병, 알츠하이머병, 노화, 심장질환, 허혈, 동맥경화, 피부질환, 염증, 류마티스, 자가면역질환, 고지혈증, 간질환, 당뇨병, 암, 만성궤양, 화상 또는 창상인 것을 특징으로 한다. In the pharmaceutical composition according to the present invention, diseases caused by the overproduction of reactive oxygen species are stroke, Parkinson's disease, Alzheimer's disease, aging, heart disease, ischemia, arteriosclerosis, skin disease, inflammation, rheumatism, autoimmune disease, It is characterized by hyperlipidemia, liver disease, diabetes, cancer, chronic ulcer, burn or wound.

본 발명에 따른 약제학적 조성물은 일반적인 경구 또는 비경구 투여 방법으로 환자에게 투여될 수 있으며, 고체 또는 액체 형태 어떠한 형태로도 가능하다. 또한, 본 발명에 따른 약제학적 조성물은 약제학적으로 허용 가능한 1종 이상의 액체 또는 고체 담체를 더 포함할 수 있다. 또한 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 상기 고체 형태의 제제에는 정제, 환제, 산제, 과립제, 캡슐제, 펠렛제, 세립제 또는 분제일 수 있으며, 이러한 고형제제는 상기 복합체에 담체, 부형제 및/또는 희석제를 첨가하여 조제할 수 있다. 상기 담체, 부형제 및/또는 희석제로는 락토오스(lactose), 수크로오스(sucrose), 덱스트로오스(dextrose), 만니톨(mannitol), 말리톨(malitol), 소르비톨(sorbitol), 자일리톨(xylitol), 에리트리톨(erithritol), 전분(starch), 아카시아고무(acacia rubber), 알지네이트(alginate), 젤라틴(gelatin), 칼슘 포스페이트(calcium phosphate), 칼슘 실리케이트(calcium silicate), 셀룰로오스(cellulose), 폴리비닐 피롤리돈(polyvinyl pyrrolidone), 마그네슘 스테아레이트(magnesium stearate) 및 광물유 등이 있다. 상기 액체 형태의 제제는 용액, 현탁액 또는 유탁액일 수 있으며, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 경구용으로 적당한 수성 현탁제로는 미분된 활성 성분을 천연 또는 합성검, 수지, 메틸셀룰로오스(methyl cellulose), 소디움카르복시메틸셀룰로오스(Sodium carboxymethyl cellulose) 및 공지의 현탁제와 같은 점성 물질에 분산시켜 제조될 수 있다. 비경구 투여제로는 주사제, 점적제, 수액, 연고, 스프레이제, 현탁제, 유제, 좌제 등을 들 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌글리콜(polyethylene glycol), 올리브 오일과 같은 식물성 오일, 에틸올레이트(ethyl oleate)와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골(macrogol), 카카오지, 라우린지, 글리세로젤라틴(glycerogelatin) 등이 사용될 수 있다.The pharmaceutical composition according to the present invention may be administered to a patient by a general oral or parenteral administration method, and may be in any form in a solid or liquid form. In addition, the pharmaceutical composition according to the present invention may further include one or more pharmaceutically acceptable liquid or solid carriers. In addition, it may be prepared by using a diluent or excipient such as a commonly used filler, extender, binder, wetting agent, disintegrant, or surfactant. The solid preparation may be a tablet, a pill, a powder, a granule, a capsule, a pellet, a fine granule, or a powder, and such a solid preparation may be prepared by adding a carrier, an excipient, and/or a diluent to the complex. Examples of the carrier, excipient and/or diluent 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 include various excipients, such as wetting agents, sweetening agents, fragrances, preservatives, etc., in addition to water and liquid paraffin, which are commonly used simple diluents. An aqueous suspension suitable for oral use is 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. I can. Examples of parenteral administration agents include injections, drops, infusions, ointments, sprays, suspensions, emulsions, and suppositories. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, cacao butter, laurin, glycerogelatin, and the like may be used.

제3구현예에 따르면,According to the third embodiment,

본 발명은 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 활성산소 과잉생성으로 인해 유발되는 질환의 예방 또는 치료용 의약외품 조성물을 제공하고자 한다. An object of the present invention is to provide a quasi-drug composition for preventing or treating diseases caused by overproduction of active oxygen, comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명에 따른 의약외품 조성물에 있어서, 상기 키토산 나노입자의 분자량은 1 내지 50kDa인 것을 특징으로 한다. In the quasi-drug composition according to the present invention, the molecular weight of the chitosan nanoparticles is characterized in that 1 to 50kDa.

본 발명에 따른 의약외품 조성물에 있어서, 상기 키토산 나노입자의 분자량은 10kDa인 것을 특징으로 한다. In the quasi-drug composition according to the present invention, the molecular weight of the chitosan nanoparticles is characterized in that 10kDa.

본 발명에 따른 의약외품 조성물에 있어서, 상기 프러시안 블루/키토산 나노입자 복합체의 크기는 1 내지 500 nm인 것을 특징으로 한다. In the quasi-drug composition according to the present invention, the Prussian blue/chitosan nanoparticle complex has a size of 1 to 500 nm.

본 발명에 따른 의약외품 조성물에 있어서, 상기 활성산소 과잉생성으로 인해 유발되는 질환은 뇌졸중, 파킨슨병, 알츠하이머병, 노화, 심장질환, 허혈, 동맥경화, 피부질환, 염증, 류마티스, 자가면역질환, 고지혈증, 간질환, 당뇨병, 암, 만성궤양, 화상 또는 창상인 것을 특징으로 한다. In the quasi-drug composition according to the present invention, the diseases caused by the overproduction of free radicals are stroke, Parkinson's disease, Alzheimer's disease, aging, heart disease, ischemia, arteriosclerosis, skin disease, inflammation, rheumatism, autoimmune disease, hyperlipidemia. , Liver disease, diabetes, cancer, chronic ulcers, burns or wounds.

본 발명에 따른 의약외품 조성물에 있어서, 상기 의약외품 조성물은 소독 청결제, 샤워폼, 가그린, 물티슈, 세제 비누, 핸드 워시, 가습기 충진제, 마스크, 연고제 또는 필터 충진제인 것을 특징으로 한다. 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, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.

제4구현예에 따르면, According to the fourth embodiment,

본 발명은 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 활성산소로 유발되는 증상 또는 질환의 예방 또는 개선용 화장료 조성물을 제공하고자 한다. An object of the present invention is to provide a cosmetic composition for preventing or improving symptoms or diseases caused by active oxygen, comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명에 따른 화장료 조성물에 있어서, 상기 활성산소로 유발되는 증상 또는 질환은 피부노화, 주름생성, 피부색소침착, 아토피, 여드름, 건선 또는 습진인 것을 특징으로 한다. In the cosmetic composition according to the present invention, the symptoms or diseases caused by the active oxygen are skin aging, wrinkles, skin pigmentation, atopy, acne, psoriasis or eczema.

본 발명에 따른 화장료 조성물에 있어서, 상기 키토산 나노입자의 분자량은 1 내지 50kDa인 것을 특징으로 한다. In the cosmetic composition according to the present invention, the molecular weight of the chitosan nanoparticles is characterized in that 1 to 50kDa.

본 발명에 따른 화장료 조성물에 있어서, 상기 키토산 나노입자의 분자량은 10kDa인 것을 특징으로 한다. In the cosmetic composition according to the present invention, the molecular weight of the chitosan nanoparticles is characterized in that 10kDa.

본 발명에 따른 화장료 조성물에 있어서, 상기 프러시안 블루/키토산 나노입자 복합체의 크기는 1 내지 500 nm인 것을 특징으로 한다. In the cosmetic composition according to the present invention, the Prussian blue/chitosan nanoparticle complex has a size of 1 to 500 nm.

본 발명에 따른 화장료 조성물에 있어서, 상기 화장료는 앰플, 크림, 로션, 화장수, 에센스 또는 팩의 형태로 제조될 수 있다. 또한, 보존이나 취급을 용이하게 하기 위하여 덱스트린(dextrin), 사이클로덱스트린(cyclodextrin) 등의 통상 제제화에 사용되는 캐리어, 그 밖의 임의의 조제를 부가하여도 좋다.In the cosmetic composition according to the present invention, the cosmetic may be prepared in the form of an ampoule, cream, lotion, lotion, essence, or pack. Further, in order to facilitate preservation and handling, a carrier commonly used in formulation, such as dextrin and cyclodextrin, and other optional preparations may be added.

제5구현예에 따르면, According to the fifth embodiment,

본 발명은 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 식품 조성물을 제공하고자 한다. The present invention is to provide a food composition comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient.

본 발명에 따른 식품 조성물에 있어서, 상기 키토산 나노입자의 분자량은 1 내지 50kDa인 것을 특징으로 한다. In the food composition according to the present invention, the chitosan nanoparticles have a molecular weight of 1 to 50 kDa.

본 발명에 따른 식품 조성물에 있어서, 상기 키토산 나노입자의 분자량은 10kDa인 것을 특징으로 한다. In the food composition according to the present invention, the molecular weight of the chitosan nanoparticles is characterized in that 10kDa.

본 발명에 따른 식품 조성물에 있어서, 상기 프러시안 블루/키토산 나노입자 복합체의 크기는 1 내지 500 nm인 것을 특징으로 한다. In the food composition according to the present invention, the Prussian blue/chitosan nanoparticle complex has a size of 1 to 500 nm.

본 발명에 따른 식품 조성물에 있어서, 상기 식품은 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 또는 비타민 복합제인 것을 특징으로 한다. In the food composition according to the present invention, the food is meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, and drinks. , An alcoholic beverage or a vitamin complex.

본 발명에 따른 식품 조성물에 있어서, 상기 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일쥬스, 과일쥬스 음료 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. In the food composition according to the present invention, the food composition includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, It may contain preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like. In addition, the composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice beverage or vegetable beverage. These components may be used independently or in combination.

본 발명에 따른 프러시안 블루/키토산 나노입자 복합체는 활성산소제거 능력 및 항균성이 뛰어나고 안정적이며 생체적합성이 우수하므로, 항산화제, 약제학적 조성물, 의약외품 조성물, 화장료 조성물 또는 식품 조성물의 개발에 효과적으로 사용될 수 있을 것으로 기대된다. The Prussian blue/chitosan nanoparticle complex according to the present invention has excellent active oxygen removal ability and antibacterial properties, is stable, and has excellent biocompatibility, so it can be effectively used in the development of antioxidants, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, or food compositions. It is expected to be there.

도 1은 본 발명에 따른 프러시안 블루/키토산 나노입자(PB/Chi NP)의 제조 방법에 대한 모식도를 나타낸다.
도 2는 프러시안 블루 나노 입자(PB NP)와 PB/키토산 나노 입자 (PB/Chi NP)의 크기를 분석한 결과를 나타낸다(도 2에서 부분적으로 침전된 나노입자 그룹은 '▲'로 표시하였다)
도 3은 PB NP와 PB/Chi NPs의 3차 증류수 내 안정성 평가 결과를 나타낸다(도 3에서 부분적으로 침전된 나노 입자의 그룹은 '▲'로 표시하였다.)
도 4는 Chitosan, PB NP와 PB/Chi NPs의 항산화력(O2·- 활성산소제거 능력)을 평가한 결과를 나타낸다.
도 5는 Chitosan, PB NP와 PB/Chi NPs의 항산화력 (OH· 활성산소제거 능력)을 평가한 결과를 나타낸다.
도 6은 PB/Chi10k NP의 농도별 세포독성 결과를 나타낸다. 1 shows a schematic diagram of a method for preparing Prussian blue/chitosan nanoparticles (PB/Chi NP) according to the present invention.
2 shows the results of analyzing the size of Prussian blue nanoparticles (PB NP) and PB/chitosan nanoparticles (PB/Chi NP) (in FIG. 2, the partially precipitated nanoparticle group is indicated by'▲' )
3 shows the results of stability evaluation of PB NPs and PB/Chi NPs in tertiary distilled water (groups of partially precipitated nanoparticles in FIG. 3 are indicated by'▲').
4 is Chitosan, NP and PB PB / Chi antioxidative ability of NPs - Results of evaluations of (O 2 · radicals removal ability).
5 shows the results of evaluating the antioxidant power (OH · active oxygen removal ability) of Chitosan, PB NP and PB/Chi NPs.
6 shows the results of cytotoxicity by concentration of PB/Chi10k NP.

이하, 발명의 이해를 돕기 위해 다양한 실시예를 제시한다. 하기 실시예는 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐 발명의 보호범위가 하기 실시예에 한정되는 것은 아니다. Hereinafter, various embodiments are presented to aid in understanding the invention. The following examples are provided for easier understanding of the invention, and the scope of protection of the invention is not limited to the following examples.

<실시예> <Example>

실시예 1. 프러시안 블루/키토산 나노 입자(PB/Chi NP)의 제조Example 1. Preparation of Prussian blue/chitosan nanoparticles (PB/Chi NP)

키토산(150mg)을 3ml의 3차 증류수(deionized water)에 녹여준 뒤 potassium ferricyanide(8.5mg, 5mM) 1ml 첨가하여 상온에서 30분 동안 450rpm으로 stirring하며 반응시켰다. 550rpm으로 stirring 하고 있는 반응용액에 iron chloride tetrahydrate(5mg, 5mM) 1ml을 천천히 dropwise해준 뒤 1시간 동안 반응시켰다. 키토산의 분자량별 (DAC90; 3, 10, 20, 50, 100 kDa)로 위의 방법을 반복해 복합체를 제조하였다. 반응 중 생성되는 KCl을 제거하기 위해 PB NP는 ultrafiltration(Amicon Ultra-15 filter)을 진행하고 PB/Chi NPs는 용액 부피 4배의 acetone(99%, Sigma aldrich)으로 침전시킨 뒤, 3일간 동결 건조하였다. PB NP와 분자량이 다른 키토산이 코팅된 PB/Chi NPs의 크기를 Zetasizer(Nano-ZS, Malvern) 장비를 이용하여 분석하였다. After dissolving chitosan (150mg) in 3ml of deionized water, 1ml of potassium ferricyanide (8.5mg, 5mM) was added and reacted with stirring at 450rpm for 30 minutes at room temperature. 1 ml of iron chloride tetrahydrate (5mg, 5mM) was slowly added dropwise to the reaction solution stirred at 550rpm and reacted for 1 hour. A composite was prepared by repeating the above method according to the molecular weight of chitosan (DAC90; 3, 10, 20, 50, 100 kDa). To remove KCl generated during the reaction, PB NPs were subjected to ultrafiltration (Amicon Ultra-15 filter), and PB/Chi NPs were precipitated with acetone (99%, Sigma aldrich) 4 times the volume of the solution, and freeze-dried for 3 days. I did. The size of PB/Chi NPs coated with chitosan having a molecular weight different from that of PB NPs was analyzed using a Zetasizer (Nano-ZS, Malvern) equipment.

그 결과, 키토산이 코팅되지 않은 PB NP는 30nm 정도의 크기로 제조되었으며, 분자량이 높은 키토산이 코팅 될수록 크기가 30nm에서 60nm까지 증가하면서 키토산의 분자량이 50kDa 및 100kDa인 경우 부분적인 침전이 발생하였다(도 2). 따라서, 키토산 라이브러리 중 PB/Chi NP를 안정적으로 제조할 수 있는 키토산 종류는 3kDa에서 20kDa까지인 것으로 확인되었다. As a result, PB NPs not coated with chitosan were prepared in a size of about 30 nm, and the size increased from 30 nm to 60 nm as chitosan with high molecular weight was coated, and partial precipitation occurred when the molecular weight of chitosan was 50 kDa and 100 kDa ( Fig. 2). Therefore, it was confirmed that the chitosan type capable of stably preparing PB/Chi NP in the chitosan library ranged from 3 kDa to 20 kDa.

<실험예><Experimental Example>

실험예 1. 프러시안 블루/키토산 나노 입자의 안정성 평가Experimental Example 1. Stability evaluation of Prussian blue/chitosan nanoparticles

동결 건조된 상기 실시예 1에서 제조된 프러시안 블루/키토산 나노입자를 3차 증류수에 분산 후 37℃, 100rpm에서 안정성 평가를 진행하였다. 이때, 상기 실시예 1에서 불안정하게 제조된 것으로 확인된 PB/Chi50k NP와 PB/Chi100k NP는 제외하였다. 시간별로 3차 증류수에서 나노 입자의 안정성을 확인하기 위해서 0일, 1일, 3일, 7일, 2주, 3주, 4주에 나노 입자의 크기 및 색상 변화를 분석하였다.After the freeze-dried Prussian blue/chitosan nanoparticles prepared in Example 1 were dispersed in third distilled water, stability was evaluated at 37° C. and 100 rpm. At this time, PB/Chi50k NP and PB/Chi100k NP, which were confirmed to be unstable in Example 1, were excluded. In order to confirm the stability of nanoparticles in tertiary distilled water by time, changes in size and color of nanoparticles were analyzed at 0, 1, 3, 7, 2, 3 and 4 weeks.

그 결과, PB NP는 3주 뒤 부분적으로 침전되었고 PB/Chi3k는 4주 뒤 부분적으로 침전되어서 안정성이 떨어지는 것으로 나타났다. PB/Chi10k NP는 4주 동안 크기 변화가 없었고 PB/Chi20k NP는 침전되진 않았지만 나노입자 크기가 4주에 걸쳐 점차 증가하는 것으로 나타났다. 따라서, 수용액 내의 안정성이 가장 뛰어난 최적화 그룹은 PB/Chi10k NP임이 확인되었다 As a result, PB NP was partially precipitated after 3 weeks and PB/Chi3k partially precipitated after 4 weeks, indicating poor stability. PB/Chi10k NP did not change in size for 4 weeks and PB/Chi20k NP did not precipitate, but nanoparticle size gradually increased over 4 weeks. Therefore, it was confirmed that the optimum group with the best stability in aqueous solution was PB/Chi10k NP.

실험예 2. 프러시안 블루/키토산 나노 입자의 활성산소제거능 평가Experimental Example 2. Evaluation of active oxygen removal ability of Prussian blue/chitosan nanoparticles

2.1 DPPH assay2.1 DPPH assay

키토산, PB NP와 PB/Chi NPs (10mg/ml)를 1ml의 3차 증류수에 녹여준 뒤 96-well plate에 150 μl 분주하였다. DPPH 용액(2mg, 0.5mM)을 methanol 10ml에 제조한 뒤 나노 입자 용액을 분주한 wells에 150 μl를 분주하였다. 상온에서 30분간 어둠 속에서 반응시켜준 후 absorbance(λ=517nm)를 측정하였다. DPPH 없이 methanol에서의 PB NP와 PB/Chi NPs의 absorbance도 측정하여 PB의 background absorbance를 배제시키고 활성산소제거능을 평가하였다. 한편, ascorbic acid(10mg/ml)를 positive control로 사용하였다. 측정된 absorbance를 바탕으로 하기의 식에 따라 항산화력을 계산하였다. Chitosan, PB NPs and PB/Chi NPs (10mg/ml) were dissolved in 1ml of distilled water and 150 μl was dispensed into a 96-well plate. After the DPPH solution (2mg, 0.5mM) was prepared in 10ml of methanol, 150 μl was dispensed into wells to which the nanoparticle solution was dispensed. After reacting in the dark for 30 minutes at room temperature, absorbance (λ = 517 nm) was measured. The absorbance of PB NPs and PB/Chi NPs in methanol without DPPH was also measured to exclude background absorbance of PB, and the ability to remove active oxygen was evaluated. Meanwhile, ascorbic acid (10mg/ml) was used as a positive control. Based on the measured absorbance, the antioxidant power was calculated according to the following equation.

Figure 112019020120335-pat00001
Figure 112019020120335-pat00001

그 결과, PB NP 자체의 항산화력(O2·- 활성산소제거 능력)은 약 20%인 반면, PB NP에 키토산(3, 10, 20kDa)을 코팅한 경우 항산화력이 현저히 증가하는 것으로 확인되었다. 그 중에서, PB/Chi10k NP의 항산화력이 가장 우수한 것으로 확인되었다(도 4).As a result, the antioxidant capacity of the PB NP itself (O 2 · - active oxygen removal capacity) when a coating of chitosan (3, 10, 20kDa) to about 20%, while, PB NP was confirmed that the antioxidant significantly increased . Among them, it was confirmed that the antioxidant power of PB/Chi10k NP was the most excellent (FIG. 4).

2.2 Hydroxyl radical assay2.2 Hydroxyl radical assay

키토산, PB NP와 PB/Chi10k NPs 용액 (3mg/ml)을 준비하였다. 15ml tube에 0.1ml EDTA(0.1mM), 0.1ml FeCl3(0.1mM), 0.1ml H2O2(1 mM), 0.1ml 2-deoxy-D-ribose(3.75 mM), 1ml 나노입자, 0.5ml phosphate buffer(20 mM)와 0.1ml ascorbic acid(0.1mM)를 넣어주었다. 하나는 H2O2와 나노입자 대신 3차 증류수를, 또 다른 하나는 나노입자 대신 3차 증류수를 넣어 control과 blank를 준비하였다. 그 후, 1시간 동안 37℃, 100rpm에서 반응시켰다. 그 다음, 15 ml NaOH(0.05 M)에 녹인 2-thiobarbituric acid(0.15g, TBA)와 15ml 3차 증류수에 녹인 trichloroacetic acid(0.3g, TCA)를 1ml씩 반응용액에 첨가하고 85℃의 water bath에서 20분간 중탕하였다. 무색이던 반응용액이 분홍색으로 변하면 96-well plate에 300μl씩 분주하고 absorbance (λ=535nm)를 측정하였다. 측정된 absorbance를 바탕으로 하기의 식에 따라 활성산소제거능력을 계산하였다. Chitosan, PB NP and PB/Chi10k NPs solution (3mg/ml) were prepared. In a 15ml tube, 0.1ml EDTA (0.1mM), 0.1ml FeCl3 (0.1mM), 0.1ml H 2 O 2 (1 mM), 0.1ml 2-deoxy-D-ribose (3.75 mM), 1ml nanoparticles, 0.5ml Phosphate buffer (20 mM) and 0.1ml ascorbic acid (0.1mM) were added. One was H 2 O 2 and tertiary distilled water instead of nanoparticles, and the other was tertiary distilled water instead of nanoparticles to prepare a control and blank. Then, it was reacted at 37° C. and 100 rpm for 1 hour. Then, 2-thiobarbituric acid (0.15g, TBA) dissolved in 15 ml NaOH (0.05 M) and trichloroacetic acid (0.3 g, TCA) dissolved in 15 ml tertiary distilled water were added to the reaction solution by 1 ml each, and a water bath at 85℃ In the bath for 20 minutes. When the colorless reaction solution turned pink, 300μl was dispensed into a 96-well plate and absorbance (λ=535nm) was measured. Based on the measured absorbance, the active oxygen removal capacity was calculated according to the following equation.

Figure 112019020120335-pat00002
Figure 112019020120335-pat00002

그 결과, PB NP, 키토산과 PB/Chi NP 그룹 모두 항산화력 (OH· 활성산소제거 능력)이 positive control인 ascorbic acid (약 25%)보다 높은 것으로 확인되었다. PB NP의 경우 약 30%의 항산화력을 나타낸 반면, PB NP에 키토산 Chi3k, Chi10k 및 Chi20k을 코팅한 경우 모두 95% 이상의 항산화력이 있는 것으로 확인되었다. As a result, it was confirmed that both the PB NP, chitosan and PB/Chi NP groups had higher antioxidant power (OH-reactive oxygen removal ability) than ascorbic acid (about 25%), which is a positive control. PB NP showed an antioxidant power of about 30%, whereas when the PB NP was coated with chitosan Chi3k, Chi10k, and Chi20k, it was found to have an antioxidant power of 95% or more.

실험예 3. 프러시안 블루/키토산 나노 입자의 세포독성 평가Experimental Example 3. Cytotoxicity evaluation of Prussian blue/chitosan nanoparticles

세포 (Raw 264.7 macrophage)를 96-well plate에 한 well당 세포 수 1Ⅹ104씩 분주하고 12시간동안 37℃, 5% CO2 환경에서 배양하였다. 세포에 다른 농도의 PB/Chi10k NP 용액 (1000, 100, 50, 20, 10 μg/ml)을 처리하고 24시간 incubation하였다. 세포 생존율은 cck-8 분석법을 통해 absorbance (λ=450nm)에서 측정하였다.Cells (Raw 264.7 macrophage) were dispensed into a 96-well plate at 1×10 4 cells per well, and cultured for 12 hours at 37°C and 5% CO 2 . Cells were treated with different concentrations of PB/Chi10k NP solutions (1000, 100, 50, 20, 10 μg/ml) and incubated for 24 hours. Cell viability was measured at absorbance (λ=450nm) through cck-8 assay.

그 결과, PB/Chi10k NP는 고농도인 1mg/ml에서도 세포독성을 일으키지 않기 때문에 생체적합성이 우수한 물질임이 입증되었다. As a result, it was proved that PB/Chi10k NP is a material having excellent biocompatibility because it does not cause cytotoxicity even at a high concentration of 1 mg/ml.

이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적 기술은 단지 바람직한 실시태양일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.As described above, specific parts of the present invention have been described in detail, and it is obvious that these specific techniques are only preferred embodiments for those of ordinary skill in the art, and the scope of the present invention is not limited thereby. something to do. Accordingly, it will be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims (10)

프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 항산화제로서,
상기 키토산 나노입자의 분자량은 3 내지 20kDa인 것을 특징으로 하는 것인, 항산화제.

As an antioxidant comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient,
The molecular weight of the chitosan nanoparticles is characterized in that 3 to 20kDa, antioxidant.

 제 1 항에 있어서,
상기 키토산 나노입자의 분자량은 10 kDa인 것을 특징으로 하는 것인, 항산화제.
The method of claim 1,
The molecular weight of the chitosan nanoparticles is characterized in that 10 kDa, antioxidant.
 제1항에 있어서,
상기 프러시안 블루/키토산 나노입자 복합체의 크기는 1 내지 500 nm인 것을 특징으로 하는 것인, 항산화제.
The method of claim 1,
The size of the Prussian blue/chitosan nanoparticle complex is 1 to 500 nm, characterized in that the antioxidant.
 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 활성산소 과잉생성으로 인해 유발되는 질환의 예방 또는 치료용 약제학적 조성물로서,
상기 키토산 나노입자의 분자량은 3 내지 20kDa이고,
상기 활성산소 과잉생성으로 인해 유발되는 질환은 뇌졸중, 파킨슨병, 알츠하이머병, 노화, 심장질환, 허혈, 동맥경화, 피부질환, 염증, 류마티스, 자가면역질환, 고지혈증, 간질환, 당뇨병, 암, 만성궤양, 화상 또는 창상인 것을 특징인 것을 특징으로 하는 것인, 약제학적 조성물.
As a pharmaceutical composition for the prevention or treatment of diseases caused by overproduction of active oxygen comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient,
The chitosan nanoparticles have a molecular weight of 3 to 20 kDa,
Diseases caused by the overproduction of free radicals include stroke, Parkinson's disease, Alzheimer's disease, aging, heart disease, ischemia, arteriosclerosis, skin disease, inflammation, rheumatism, autoimmune disease, hyperlipidemia, liver disease, diabetes, cancer, chronic The pharmaceutical composition, which is characterized in that it is an ulcer, a burn or a wound.
 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 활성산소 과잉생성으로 인해 유발되는 질환의 예방 또는 치료용 의약외품 조성물로서,
상기 키토산 나노입자의 분자량은 3 내지 20kDa이고,
상기 활성산소 과잉생성으로 인해 유발되는 질환은 뇌졸중, 파킨슨병, 알츠하이머병, 노화, 심장질환, 허혈, 동맥경화, 피부질환, 염증, 류마티스, 자가면역질환, 고지혈증, 간질환, 당뇨병, 암, 만성궤양, 화상 또는 창상인 것을 특징인 것을 특징으로 하는 것인, 의약외품 조성물.
As a quasi-drug composition for preventing or treating diseases caused by overproduction of active oxygen comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient,
The chitosan nanoparticles have a molecular weight of 3 to 20 kDa,
Diseases caused by the overproduction of free radicals include stroke, Parkinson's disease, Alzheimer's disease, aging, heart disease, ischemia, arteriosclerosis, skin disease, inflammation, rheumatism, autoimmune disease, hyperlipidemia, liver disease, diabetes, cancer, chronic The quasi-drug composition, characterized in that it is characterized by an ulcer, a burn or a wound.
 제5항에 있어서,
상기 의약외품 조성물은 소독 청결제, 샤워폼, 가그린, 물티슈, 세제 비누, 핸드 워시, 가습기 충진제, 마스크, 연고제 또는 필터 충진제인 것을 특징으로 하는 것인, 의약외품 조성물.
The method of claim 5,
The quasi-drug composition is characterized in that the disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 활성산소로 유발되는 증상 또는 질환의 예방 또는 개선용 화장료 조성물로서,
상기 키토산 나노입자의 분자량은 3 내지 20kDa이고,
상기 활성산소로 유발되는 증상 또는 질환은 피부노화, 주름생성, 피부색소침착, 아토피, 여드름, 건선 또는 습진인 것을 특징으로 하는 것인, 화장료 조성물.
As a cosmetic composition for preventing or improving symptoms or diseases caused by active oxygen comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient,
The chitosan nanoparticles have a molecular weight of 3 to 20 kDa,
The symptoms or diseases caused by the free radicals are skin aging, wrinkles, skin pigmentation, atopy, acne, psoriasis or eczema.
 제7항에 있어서,
상기 화장료는 앰플, 크림, 로션, 화장수, 에센스 또는 팩인 것을 특징으로 하는 것인, 화장료 조성물.
The method of claim 7,
The cosmetic composition is characterized in that the ampoule, cream, lotion, lotion, essence or pack.
 프러시안 블루/키토산 나노입자 복합체를 유효 성분으로 포함하는 식품 조성물로서,
상기 키토산 나노입자의 분자량은 3 내지 20kDa인 것을 특징으로 하는 것인, 식품 조성물.
A food composition comprising a Prussian blue/chitosan nanoparticle complex as an active ingredient,
The chitosan nanoparticles have a molecular weight of 3 to 20 kDa, characterized in that the food composition.
 제9항에 있어서,
상기 식품은 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 또는 비타민 복합제를 특징으로 하는 것인, 식품 조성물. The method of claim 9,
The food is characterized by meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, or vitamin complexes. That is, food composition.
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