KR102221453B1 - An oral mucoadhesive film composition comprising a low molecular weight collagen peptide and a natural extract compound and an oral mucoadhesive film prepared using the same - Google Patents

An oral mucoadhesive film composition comprising a low molecular weight collagen peptide and a natural extract compound and an oral mucoadhesive film prepared using the same Download PDF

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KR102221453B1
KR102221453B1 KR1020190087753A KR20190087753A KR102221453B1 KR 102221453 B1 KR102221453 B1 KR 102221453B1 KR 1020190087753 A KR1020190087753 A KR 1020190087753A KR 20190087753 A KR20190087753 A KR 20190087753A KR 102221453 B1 KR102221453 B1 KR 102221453B1
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oral mucosa
film
modified starch
collagen peptide
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KR20210010177A (en
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김대익
김동섭
성낙윤
한인준
서지영
엄지
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한국프라임제약주식회사
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0204Specific forms not provided for by any of groups A61K8/0208 - A61K8/14
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/345Alcohols containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/65Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/732Starch; Amylose; Amylopectin; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations

Abstract

본 발명은 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물 및 이를 이용하여 제조된 구강점막부착형 필름에 관한 것으로, 그 구성은, 피부노화 방지, 주름개선, 피부탄력강화, 미백 기능을 발휘하는 분자량 1×104 dalton 이하의 저분자 콜라겐 펩타이드와, 수분보유량, 표피유연성 증대 및 피부탄력 개선 기능을 발휘하는 엘라스틴 펩타이드와, 접착성과 조막성을 갖는 수용성 플루란과, 본래의 구조나 물성을 변형시킨 산처리화 변성전분, 하이드록시프로필화 변성전분, α화 변성전분 중 어느 하나의 변성전분ㄱ고과, 공기 중의 수분을 흡수하여 보습제로의 기능을 부여하 글리세린과, 필름의 인장강도를 증대시키기 위해 함유되는 카라기난과, 구강 내에 적용하더라도 쓴맛을 차폐하는 아스파탐과, 항염증, 항산화 작용을 하는 비타민나무 열매 추출물, 블랙베리 잎 추출물%, 자소엽 추출물로 구성되는 천연추출복합물과, 친수성 및 흡습성 기능을 발휘하는 폴리아크릴산나트륨으로 이루어진다.The present invention relates to an oral mucosa-attached film composition comprising a low-molecular collagen peptide and a natural extract complex, and an oral mucosa-attachable film prepared using the same, the composition of which is to prevent skin aging, improve wrinkles, strengthen skin elasticity, and whitening A low-molecular collagen peptide with a molecular weight of 1×10 4 dalton or less that exhibits a function, an elastin peptide that has a function of increasing moisture retention, epidermal flexibility and improving skin elasticity, a water-soluble flurane having adhesiveness and film formation, and its original structure Denatured starch ㄱ of any one of acid-treated modified starch, hydroxypropylated modified starch, and α-modified starch with modified physical properties, glycerin that absorbs moisture in the air to give it a function as a moisturizing agent, and the tensile strength of the film A natural extract complex consisting of carrageenan, which masks bitter taste even when applied in the oral cavity, and vitamin tree fruit extract that has anti-inflammatory and antioxidant properties, blackberry leaf extract%, perilla leaf extract, and hydrophilicity And sodium polyacrylate exhibiting a hygroscopic function.

Description

저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물 및 이를 이용하여 제조된 구강점막부착형 필름{An oral mucoadhesive film composition comprising a low molecular weight collagen peptide and a natural extract compound and an oral mucoadhesive film prepared using the same}An oral mucoadhesive film composition comprising a low molecular weight collagen peptide and a natural extract compound and an oral mucoadhesive film prepared using the same prepared using the same}

본 발명은 피부노화 방지, 주름개선, 피부탄력강화, 미백 등 피부 미용에 활성화를 갖는 저분자 콜라겐과 각종 천연추출복합 성분을 구강점막에 부착되는 필름형으로 제조하여 피부 진피 흡수율을 증대시키고 간편하게 구강 내에서 적용할 수 있도록 한 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물 및 이를 이용하여 제조된 구강점막부착형 필름에 관한 것이다.The present invention is to increase the absorption rate of the skin dermis and increase the absorption rate of the skin by producing a low-molecular collagen and various natural extract complex ingredients that are active in skin beauty such as skin aging prevention, wrinkle improvement, skin elasticity, and whitening in a film type attached to the oral mucosa. It relates to an oral mucosa-attached film composition comprising a low-molecular collagen peptide and a natural extract complex that can be applied in, and an oral mucosa-attached film prepared using the same.

콜라겐은 인간의 신체에 여러 장기와 몸의 형체를 만들고 지지해 주는 핵심적인 역할을 한다고 알려져 있으며 최근 성형 수술이나 재건 수술 등 의료계통으로도 많은 관심을 보이고 있다. 화장품 제품으로도 잔주름, 기미, 노화방지, 색소침착, 피부재생 등의 기능성 제품이 생산되고 있는 추세이다. 콜라겐은 동물이나 해양 생물의 피부, 뼈 및 조직 등의 부산물에서 얻을 수 있으며, 글리신(glycine), 프롤린(proline), 하이드록시 프롤린(hydroxyl proline), 아르기닌(arginine) 등 필수아미노산을 포함한다.Collagen is known to play a key role in creating and supporting various organs and body shapes in the human body, and recently, it is showing a lot of interest in the medical system such as plastic surgery and reconstructive surgery. Functional products such as fine wrinkles, blemishes, anti-aging, pigmentation, and skin regeneration are also being produced as cosmetics products. Collagen can be obtained from by-products such as skin, bones and tissues of animals or marine organisms, and contains essential amino acids such as glycine, proline, hydroxyl proline, and arginine.

그러나 동물 및 해양 생물의 부산물인 콜라겐은 단백질로 이루어져 있고 대부분이 고분자량이므로, 인간의 피부를 통해 흡수될 수 없어 콜라겐 식품 또는 화장품에 사용하기에 적합하지 않은 문제점을 내재하고 있었다.However, collagen, which is a by-product of animals and marine organisms, is composed of proteins and most of them are of high molecular weight, so it cannot be absorbed through human skin, so it has an inherent problem that is not suitable for use in collagen foods or cosmetics.

이에, 본 발명의 발명자들은 콜라겐의 인체에 대한 흡수력을 최대화시킬 수 있는 조성물을 예의 연구한 결과, 구강점막을 통한 콜라겐 흡수가 일반 피부를 통해 흡수되는 양 보다 현저히 많고, 특히 저분자화된 펩타이드는 피부노화 방지, 피부탄력 개선, 주름개선, 피부 노화 방지, 미백 등에 효과적임을 실험을 통해 확인하고, 본 발명을 완성하였다.Accordingly, the inventors of the present invention have studied a composition capable of maximizing the absorption power of collagen to the human body, and as a result, collagen absorption through the oral mucosa is significantly greater than the amount absorbed through normal skin. It was confirmed through experiments that it was effective in anti-aging, skin elasticity improvement, wrinkle improvement, skin aging prevention, whitening, etc., and the present invention was completed.

미국 등록특허 제08840935호(Orally administrable films and preparation thereof, 2014.09.23.)US Patent No. 08840935 (Orally administrable films and preparation thereof, 2014.09.23.) 미국 등록특허 제10272038호(Film dosage form with extended release mucoadhesive particles, 2019.04.30.)U.S. Patent No. 10272038 (Film dosage form with extended release mucoadhesive particles, April 30, 2019) 일본 공개특허 제2017-206531호(Transmucosal administration system for a pharmaceutical drug, 2017.11.24.)Japanese Patent Laid-Open No. 2017-206531 (Transmucosal administration system for a pharmaceutical drug, 2017.11.24.)

본 발명은 종래의 고분자 콜라겐이 갖는 문제점을 해결하기 위한 일환으로 창안된 것으로, 본 발명의 목적은 피부노화 방지, 주름개선, 피부탄력강화, 미백 등 피부 미용에 활성화를 갖는 저분자 콜라겐과 각종 천연추출복합 성분을 구강점막에 부착되는 필름형으로 제조하여 피부 진피 흡수율을 증대시키고 간편하게 구강 내에 적용할 수 있으며, 또 저분자화된 콜라겐 펩타이드를 주성분으로 하여 체내 흡수율을 높일 수 있는 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물 및 이를 이용하여 제조된 구강점막부착형 필름을 제공함에 있다.The present invention was invented as a part of solving the problems of the conventional high molecular collagen, and the object of the present invention is to prevent skin aging, improve wrinkles, strengthen skin elasticity, whitening, etc. A low-molecular collagen peptide and natural extract complex that increases the absorption rate of the skin dermis and can be easily applied to the oral cavity by manufacturing a complex component in a film form attached to the oral mucosa. Also, a low-molecular collagen peptide is used as the main component to increase the absorption rate in the body. To provide an oral mucosa-attached film composition comprising a and an oral mucosa-attached film prepared using the same.

상기 목적을 달성하기 위한 본 발명의 과제 해결 수단 구성은,
피부노화 방지, 주름개선, 피부탄력강화, 미백 기능을 발휘하는 분자량 1×104 dalton 이하의 저분자 콜라겐 펩타이드(low-molecular weight collagen peptide) 1.5 - 22.0중량%, 수분보유량, 표피유연성 증대 및 피부탄력 개선 기능을 발휘하는 엘라스틴 펩타이드(elastin peptide) 0.1 - 1.0중량%, 접착성과 조막성을 갖는 수용성 플루란(pullulan) 50.0 - 54.0중량%, 본래의 구조나 물성을 변형시킨 산처리화 변성전분, 하이드록시프로필화 변성전분, α화 변성전분 중 어느 하나의 변성전분(modified starch) 10.0 - 13.0중량%, 공기 중의 수분을 흡수하여 보습제로의 기능을 부여하 글리세린(glycerin) 10.0 - 13.0중량%, 필름의 인장강도를 증대시키기 위해 함유되는 카라기난(carrageenan) 0.6 - 2.0중량%, 구강 내에 적용하더라도 쓴맛을 차폐하는 아스파탐 6.2 - 13.5중량%, 항염증, 항산화 작용을 하는 비타민나무 열매 추출물 15.0 - 32.0중량%, 블랙베리 잎 추출물 65.0 - 75.0중량%, 자소엽 추출물 3.0 - 10.0중량%로 구성되는 천연추출복합물 1.0 - 1.5중량%, 친수성 및 흡습성 기능을 발휘하는 폴리아크릴산나트륨(sodium polyacrylate) 0.1 - 0.5중량%; 로 이루어진다.
The configuration of the problem solving means of the present invention for achieving the above object,
Low-molecular weight collagen peptide 1.5-22.0% by weight with a molecular weight of 1×10 4 dalton or less, exhibiting skin aging prevention, wrinkle improvement, skin elasticity, and whitening functions, moisture retention, increased epidermal flexibility and skin elasticity 0.1-1.0% by weight of elastin peptide that exhibits improved function, 50.0-54.0% by weight of water-soluble pullulan with adhesive and film-forming properties, acid-treated modified starch with modified original structure or physical properties, and hide Modified starch of either oxypropylated modified starch or α-modified starch 10.0-13.0 wt%, Glycerin 10.0-13.0 wt%, which absorbs moisture in the air and gives it a function as a moisturizing agent, film 0.6-2.0% by weight of carrageenan contained to increase the tensile strength of, 6.2-13.5% by weight of aspartame that masks bitter taste even when applied in the oral cavity, 15.0-32.0% by weight of vitamin tree fruit extract that has anti-inflammatory and antioxidant effects , Blackberry leaf extract 65.0-75.0% by weight, natural extract complex consisting of 3.0-10.0% by weight of perilla leaf extract 1.0-1.5% by weight, sodium polyacrylate 0.1-0.5% by weight exhibiting hydrophilic and hygroscopic functions ; Consists of

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본 발명에 따른 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물 및 이를 이용하여 제조된 구강점막부착형 필름은,An oral mucosa-attached film composition comprising a low-molecular collagen peptide and a natural extract complex according to the present invention, and an oral mucosa-attached film prepared using the same,

첫째, 피부노화 방지, 주름개선, 피부탄력강화, 미백 등 피부 미용에 활성화를 갖는 성분을 구강점막필름형으로 제조하여 간편하게 구강 내에 적용할 수 있고,First, ingredients that are active in skin beauty such as skin aging prevention, wrinkle improvement, skin elasticity, whitening, etc. can be manufactured in the form of an oral mucosa film and can be conveniently applied in the oral cavity.

둘째, 분자량이 1×104 dalton 이하인 저분자 콜라겐 펩타이드를 주성분으로 하여 체내 흡수율을 높일 수 있으며,Second, the absorption rate in the body can be increased by using a low-molecular collagen peptide with a molecular weight of 1×10 4 dalton or less as a main component.

셋째, 비타민나무 열매, 블랙베리 잎, 자소엽으로 구성된 천연추출복합물의 함유로 피부 미용 등의 효과에 더욱 유의적으로 작용한다.Third, it works more significantly on effects such as skin beauty by containing a natural extract complex composed of vitamin tree fruit, blackberry leaf, and perilla leaf.

도 1은 3D 구강점막 세포를 이용한 저분자 콜라겐 투과율 평가에서 구강점막 세포에 투과된 고분자 콜라겐과 본 발명에 따른 저분자 콜라겐의 흡수양을 측정한 그래프.
도 2는 3D 구강점막 세포를 이용한 저분자 콜라겐 투과율 평가에서 구강점막 세포에 고분자 콜라겐과 본 발명에 따른 저분자 콜라겐의 투과도를 형광 표지로 나타낸 사진.
도 3은 본 발명에 따른 구강점막부착형 필름의 함량에 따른 Elastase 활성 억제효과를 평가한 그래프.
도 4는 본 발명에 따른 구강점막부착형 필름의 함량에 따른 Collagenase 활성 억제효과를 평가한 그래프.
도 5는 본 발명에 따른 구강점막부착형 필름의 함량에 따른 Type-1 procollagen 합성 촉진 활성을 평가한 그래프.
도 6은 본 발명에 따른 구강점막부착형 필름의 함량에 따른 항산화 효과를 평가한 그래프.
도 7은 본 발명에 따른 구강점막부착형 필름의 Tyrosinase 억제 활성 평가를 통한 미백 효과를 평가한 그래프.
도 8은 본 발명에 따른 구강점막부착형 필름의 피부 주름 개선 효과를 평가한 그래프.
도 9는 본 발명에 따른 구강점막부착형 필름의 피부 탄력 향상 효과를 평가한 그래프.
1 is a graph measuring the amount of absorption of high molecular collagen permeated to oral mucosa cells and low molecular collagen according to the present invention in the evaluation of low molecular weight collagen permeability using 3D oral mucosa cells.
Figure 2 is a photograph showing the permeability of the high molecular collagen and the low molecular collagen according to the present invention to the oral mucosa cells in the evaluation of the permeability of low molecular collagen using 3D oral mucosa cells with a fluorescent label.
3 is a graph evaluating the effect of inhibiting the Elastase activity according to the content of the oral mucosa-attached film according to the present invention.
4 is a graph evaluating the effect of inhibiting collagenase activity according to the content of the oral mucosa-attached film according to the present invention.
5 is a graph evaluating the activity of promoting Type-1 procollagen synthesis according to the content of the oral mucosa-attached film according to the present invention.
6 is a graph evaluating the antioxidant effect according to the content of the oral mucosa-attached film according to the present invention.
7 is a graph evaluating the whitening effect through the evaluation of the Tyrosinase inhibitory activity of the oral mucosa-attached film according to the present invention.
8 is a graph evaluating the effect of improving skin wrinkles of the oral mucosa-attached film according to the present invention.
9 is a graph evaluating the effect of improving skin elasticity of the oral mucosa-attached film according to the present invention.

이하, 본 발명의 바람직한 실시예에 따른 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물에 대하여 상세하게 설명한다.Hereinafter, an oral mucosa-attached film composition comprising a low molecular weight collagen peptide and a natural extract complex according to a preferred embodiment of the present invention will be described in detail.

본 발명의 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물은,Oral mucosa-attached film composition comprising the low-molecular collagen peptide and natural extract complex of the present invention,

피부노화 방지, 주름개선, 피부탄력강화, 미백 기능을 발휘하는 분자량 1×104 dalton 이하의 저분자 콜라겐 펩타이드(low-molecular weight collagen peptide) 1.5 - 22.0중량%, 수분보유량, 표피유연성 증대 및 피부탄력 개선 기능을 발휘하는 엘라스틴 펩타이드(elastin peptide) 0.1 - 1.0중량%, 접착성과 조막성을 갖는 수용성 플루란(pullulan) 50.0 - 54.0중량%, 본래의 구조나 물성을 변형시킨 산처리화 변성전분, 하이드록시프로필화 변성전분, α화 변성전분 중 어느 하나의 변성전분(modified starch) 10.0 - 13.0중량%, 공기 중의 수분을 흡수하여 보습제로의 기능을 부여하 글리세린(glycerin) 10.0 - 13.0중량%, 필름의 인장강도를 증대시키기 위해 함유되는 카라기난(carrageenan) 0.6 - 2.0중량%, 구강 내에 적용하더라도 쓴맛을 차폐하는 아스파탐 6.2 - 13.5중량%, 항염증, 항산화 작용을 하는 비타민나무 열매 추출물 15.0 - 32.0중량%, 블랙베리 잎 추출물 65.0 - 75.0중량%, 자소엽 추출물 3.0 - 10.0중량%로 구성되는 천연추출복합물 1.0 - 1.5중량%, 친수성 및 흡습성 기능을 발휘하는 폴리아크릴산나트륨(sodium polyacrylate) 0.1 - 0.5중량%; 로 이루어진다. Low-molecular weight collagen peptide 1.5-22.0% by weight with a molecular weight of 1×10 4 dalton or less, exhibiting skin aging prevention, wrinkle improvement, skin elasticity, and whitening functions, moisture retention, increased epidermal flexibility and skin elasticity 0.1-1.0% by weight of elastin peptide that exhibits improved function, 50.0-54.0% by weight of water-soluble pullulan with adhesive and film-forming properties, acid-treated modified starch with modified original structure or physical properties, and hide Modified starch of either oxypropylated modified starch or α-modified starch 10.0-13.0 wt%, Glycerin 10.0-13.0 wt%, which absorbs moisture in the air and gives it a function as a moisturizing agent, film 0.6-2.0% by weight of carrageenan contained to increase the tensile strength of, 6.2-13.5% by weight of aspartame that masks bitter taste even when applied in the oral cavity, 15.0-32.0% by weight of vitamin tree fruit extract that has anti-inflammatory and antioxidant effects , Blackberry leaf extract 65.0-75.0% by weight, natural extract complex consisting of 3.0-10.0% by weight of perilla leaf extract 1.0-1.5% by weight, sodium polyacrylate 0.1-0.5% by weight exhibiting hydrophilic and hygroscopic functions ; Consists of

상기 저분자 콜라겐 펩타이드는 피부노화 방지, 주름개선, 피부탄력강화, 미백 등 미용에 탁월한 효과를 발휘하는 성분으로, 본 발명에서는 피부 진피 흡수가 용이하게 이루어지도록 콜라겐 펩타이드(경단백질 또는 알부미노이드 등)를 물리적 처리, 화학적 처리 및 생물학적 처리 중에서 어느 하나 이상의 처리에 의한 기작으로 저분자화하여 분자량이 1×104 dalton 이하가 되도록 한다. 이를테면, 세포벽을 파쇄하여 저분자화하거나, 가수분해 처리 등을 통하여 저분자화할 수 있다.The low molecular weight collagen peptide is a component that exhibits excellent effects on beauty such as preventing skin aging, improving wrinkles, strengthening skin elasticity, and whitening. In the present invention, collagen peptides (such as light proteins or albuminoids) to facilitate absorption of the skin dermis The molecular weight is reduced to 1×10 4 dalton or less by reducing the molecular weight by a mechanism by any one or more of physical treatment, chemical treatment, and biological treatment. For example, the cell wall may be crushed to make it low molecular weight, or it may be made low molecular weight through hydrolysis treatment or the like.

이로써, 저분자량을 갖는 콜라겐 펩타이드는 적용영역에서 흡수가 용이하도록 하여 혈중농도가 빠르게 증가함으로 인해 소망하는 피부 미용효과를 달성할 수 있게 되는 것이다.As a result, the collagen peptide having a low molecular weight is easily absorbed in the application area, so that the blood concentration increases rapidly, thereby achieving a desired skin cosmetic effect.

본 발명의 바람직한 일 실시예에 따르면, 상기 저분자 콜라겐 펩타이드는 조성물 총 중량 대비 1.5 내지 22.0중량%로 함유된다. 상기 저분자 콜라겐 펩타이드가 1.5중량% 미만으로 함유되면 피부 진피에 흡수되는 양이 미미하여 콜라겐이 지닌 기능성이 충분히 발휘되지 못하고, 22.0중량%를 초과하여 함유되면 타 성분과의 원활한 밸런스를 유지하지 못하여 구강점막 내에 적용하더라도 소망하고자 하는 피부 미용효과를 달성하기 어렵다.According to a preferred embodiment of the present invention, the low molecular weight collagen peptide is contained in an amount of 1.5 to 22.0% by weight based on the total weight of the composition. If the low molecular weight collagen peptide is contained in less than 1.5% by weight, the amount absorbed into the skin dermis is insignificant, so that the functionality of the collagen cannot be sufficiently exhibited, and if it is contained in more than 22.0% by weight, the oral mucosa cannot maintain a smooth balance with other ingredients. Even if it is applied within, it is difficult to achieve the desired skin beauty effect.

상기 엘라스틴 펩타이드는 수분보유량, 표피유연성 증대와 피부 탄력을 개선하는 기능이 탁월한 성분으로, 본 발명의 바람직한 일 실시예에 따르면, 상기 엘라스틴 펩타이드는 조성물 총 중량 대비 0.1 내지 1.0중량%로 함유된다. 상기 엘라스틴 펩타이드가 0.1중량% 미만으로 함유되면 수분보유량, 표피유연성 증대 및 피부 탄력 개선과 같은 효과를 발휘하지 못하며, 1.0중량%를 초과하여 함유되면 조성물을 조성하는 성분들 사이에 밸런스가 무너져 구강점막 내에서 유효한 기능 작동이 원활하게 이루어지지 않는다.The elastin peptide is a component having excellent functions of retaining moisture, increasing epidermal flexibility and improving skin elasticity.According to a preferred embodiment of the present invention, the elastin peptide is contained in an amount of 0.1 to 1.0% by weight based on the total weight of the composition. If the elastin peptide is contained in an amount of less than 0.1% by weight, effects such as moisture retention, epidermal flexibility and skin elasticity improvement cannot be exerted, and if it is contained in excess of 1.0% by weight, the balance between the components constituting the composition is broken and the oral mucosa Functions that are valid within are not working smoothly.

상기 플루란은 수용성이며 접착성이 강하고 조막성이 우수한 특성이 있다. 본 발명의 바람직한 일 실시예에 따르면, 상기 플루란은 조성물 총 중량 대비 50.0 내지 54.0중량%로 함유된다. 상기 플루란이 50.0중량% 미만으로 함유되면 필름 형태로의 가공이 용이하지 않고, 54.0중량%를 초과하여 함유되면 필요 이상의 양이 함유되어 비경제적이다.The flurane is water-soluble, has strong adhesion, and has excellent film-forming properties. According to a preferred embodiment of the present invention, the fluran is contained in an amount of 50.0 to 54.0% by weight based on the total weight of the composition. If the flurane is contained in an amount of less than 50.0% by weight, processing into a film form is not easy, and if it is contained in an amount exceeding 54.0% by weight, it is uneconomical because it contains more than necessary amount.

상기 변성전분은 전분에 각종 가공처리를 하여 본래의 구조나 물성을 변형시킨 것으로, 본 발명에서는 산처리화 변성전분, 하이드록시프로필화 변성전분, α화 변성전분, 전분 분해물로 된 변성전분 중에서 선택된 어느 하나 이상을 사용할 수 있다.The modified starch is a modified starch that has undergone various processing treatments to modify its original structure and physical properties.In the present invention, it is selected from modified starch consisting of acid-treated modified starch, hydroxypropylated modified starch, α-modified starch, and starch decomposition product. Any one or more can be used.

본 발명의 바람직한 일 실시예에 따르면, 상기 변성전분은 조성물 총 중량 대비 10.0 내지 13.0중량%로 함유된다. 상기 변성전분이 10.0중량% 미만으로 함유되면 수용액상에서 구형의 분자구조를 보여 필름의 인장강도가 약해지거나 필름이 형성되지 않을 수 있고, 13.0중량%를 초과하여 함유되면 부분적으로 불규칙한 미쉘 구조를 형성하여 분자 내부에 응집현상을 유발하여 필름화를 할 수 없게 된다.According to a preferred embodiment of the present invention, the modified starch is contained in an amount of 10.0 to 13.0% by weight based on the total weight of the composition. If the modified starch is contained in an amount of less than 10.0% by weight, it shows a spherical molecular structure in an aqueous solution, so that the tensile strength of the film may be weakened or the film may not be formed. It causes an agglomeration phenomenon inside the molecule, making it impossible to form a film.

상기 글리세린은 공기 중의 수분을 흡수하여 보습제로의 기능을 부여하기 위해 함유되는 것으로, 본 발명의 바람직한 일 실시예에 따르면, 조성물 총 중량 대비 10.0 내지 13.0중량%로 함유된다. 상기 글리세린이 10.0중량% 미만으로 함유되면 보습제로의 기능을 발휘하지 못하고, 13.0중량%를 초과하여 함유되면 필름 표면에 점착성 및 신율을 증가시켜 사용상에 문제가 발생할 수 있다.The glycerin is contained in order to impart a function as a moisturizing agent by absorbing moisture in the air, and according to a preferred embodiment of the present invention, it is contained in an amount of 10.0 to 13.0% by weight based on the total weight of the composition. When the glycerin is contained in an amount of less than 10.0% by weight, it does not function as a moisturizing agent, and when it is contained in an amount exceeding 13.0% by weight, the adhesiveness and elongation on the film surface may be increased, resulting in a problem in use.

상기 카라기난은 홍조류에 속하는 해조들의 열수추출물로서 갈락토오스를 반복단위로 하는 갈락탄류의 기본 구조를 갖고 있으며, 구성 단위들은 모두 황산에스터형 또는 무수형으로 되어 있다. 상기 카라기난은 필름의 인장강도를 증대시키기 위해 함유되며, 본 발명의 바람직한 일 실시예에 따르면, 조성물 총 중량 대비 0.6 내지 2.0중량%로 함유된다. 상기 카라기난이 0.6중량% 미만으로 함유되면 충분한 인장강도를 발휘하지 못하고, 2.0중량%를 초과하면 인장강도가 과도하게 증대되어 가공 또는 절단작업이 용이하지 않다.The carrageenan is a hot water extract of seaweeds belonging to red algae, and has a basic structure of galactans having galactose as a repeating unit, and all of the structural units are sulfuric acid ester type or anhydrous type. The carrageenan is contained to increase the tensile strength of the film, and according to a preferred embodiment of the present invention, it is contained in an amount of 0.6 to 2.0% by weight based on the total weight of the composition. When the carrageenan is contained in an amount of less than 0.6% by weight, sufficient tensile strength is not exhibited, and when it exceeds 2.0% by weight, the tensile strength is excessively increased, making it difficult to process or cut.

상기 감미료는 쓴맛을 차폐하여 구강 내에 적용하더라도 불쾌감이 없도록 하기 위한 것으로, 본 발명에서는 비타민 C(vitamin C), 아스파탐(aspartame), 자일리톨(xylitol), 레몬향(lemon flavor) 중에서 선택된 어느 하나 또는 이들의 조합으로 이루어질 수 있다.The sweetener is intended to shield the bitter taste so that there is no discomfort even when applied in the oral cavity.In the present invention, any one selected from vitamin C (vitamin C), aspartame, xylitol, and lemon flavor, or these It can be made of a combination of.

본 발명의 바람직한 일 실시예에 따르면, 상기 감미료는 조성물 총 중량 대비 6.2 내지 13.5중량%로 함유된다. 상기 감미료가 6.2중량% 미만으로 함유되면 감미료의 기능이 미미하고, 13.5중량%를 초과하면 감미료의 향이 강해져 오히려 불쾌감을 유발할 수 있다.According to a preferred embodiment of the present invention, the sweetener is contained in an amount of 6.2 to 13.5% by weight based on the total weight of the composition. If the sweetener is contained in an amount of less than 6.2% by weight, the function of the sweetener is insignificant, and if it exceeds 13.5% by weight, the flavor of the sweetener becomes strong, which may cause discomfort.

상기 천연추출복합물은 비타민나무 열매 추출물과, 블랙베리 잎 추출물 및 자소엽 추출물로 구성된 것으로, 본 발명의 바람직한 일 실시예에 따르면, 상기 천연추출복합물은 비타민나무 열매 추출물 15.0 내지 32.0중량%, 블랙베리 잎 추출물 65.0 내지 75.0중량% 및 자소엽 추출물 3.0 내지 10.0중량%로 구성될 수 있다.The natural extract complex is composed of a vitamin tree fruit extract, a blackberry leaf extract and a perilla leaf extract, and according to a preferred embodiment of the present invention, the natural extract complex is a vitamin tree fruit extract 15.0 to 32.0% by weight, blackberry It may consist of 65.0 to 75.0% by weight of leaf extract and 3.0 to 10.0% by weight of perilla leaf extract.

상기 비타민나무 열매 추출물을 얻기 위한 대상체인 비타민나무는 비타민과 베타-카로틴(β-carotene) 성분을 다량 함유하고 있으며, 본 발명의 바람직한 일 실시예에 의하면, 상기 비타민나무 열매 추출물은 천연추출복합물 총 중량 대비 15.0 내지 32.0중량%로 함유될 수 있다. 상기 비타민나무 열매 추출물이 32.0중량%를 초과할 경우 소망하고자 하는 기능적 작용인 항염증, 항산화 작용 등은 충분히 나타나나 필요 이상의 양이 첨가됨으로 인해 비경제적인 문제가 따르고, 15.0중량% 미만일 경우 그 첨가량이 미미하여 항염증, 항산화 작용 등 소망하고자 하는 기능적 작용을 기대하기 어렵다.The vitamin tree, which is an object for obtaining the vitamin tree fruit extract, contains a large amount of vitamins and beta-carotene, and according to a preferred embodiment of the present invention, the vitamin tree fruit extract is a natural extract complex. It may be contained in an amount of 15.0 to 32.0% by weight based on the weight. When the vitamin tree fruit extract exceeds 32.0% by weight, the desired functional effects such as anti-inflammatory and antioxidant activities are sufficiently exhibited, but an uneconomic problem occurs due to the addition of an amount more than necessary, and when the amount is less than 15.0% by weight, the added amount As it is insignificant, it is difficult to expect desired functional effects such as anti-inflammatory and antioxidant effects.

상기 블랙베리 잎 추출물을 얻기 위한 대상체인 블랙베리는 간, 신장, 방광기능을 좋게 하며, 항암 및 항산화 작용에 유익한 유효성분의 함량이 매우 높다.Blackberry, which is a subject for obtaining the blackberry leaf extract, improves liver, kidney, and bladder functions, and has a very high content of active ingredients that are beneficial for anticancer and antioxidant activities.

본 발명의 바람직한 일 실시예에 의하면, 상기 블랙베리 잎 추출물은 천연추출복합물 총 중량 대비 65.0 내지 75.0중량%로 함유될 수 있다. 상기 블랙베리 잎 추출물이 75.0중량%를 초과할 경우 블랙베리 잎 추출물의 기능적 작용은 우수해지는 반면, 블랙베리 잎 추출물을 제외한 나머지 성분의 기능적 작용은 상대적으로 열등해짐에 따라 다양한 경로를 통해 발생하는 피부질환 발생 원인인자 중 일부만을 표적하게 되고, 그 결과 피부 관리의 효율성이 낮아지게 되며, 65.0중량% 미만일 경우 블랙베리 잎의 기능적 작용의 저하, 즉 항염증 작용 및 항산화 작용이 미미해진다.According to a preferred embodiment of the present invention, the blackberry leaf extract may be contained in an amount of 65.0 to 75.0% by weight based on the total weight of the natural extract complex. When the amount of the blackberry leaf extract exceeds 75.0% by weight, the functional action of the blackberry leaf extract becomes excellent, whereas the functional action of the remaining ingredients except for the blackberry leaf extract becomes relatively inferior, resulting in skin occurring through various routes. It targets only some of the factors causing the disease, and as a result, the efficiency of skin care decreases. If it is less than 65.0% by weight, the functional action of the blackberry leaf decreases, that is, the anti-inflammatory action and antioxidant action are insignificant.

상기 자소엽 추출물을 얻기 위한 대상체인 자소엽은 꿀풀과(Labiatae)에 속하는 1년생 초본으로 현대 의학에서는 항염증, 항알러지, 항천식, 항산화 작용 등에 효과가 있다고 알려져 있다.Perilla lobules, which are subjects for obtaining the perilla lobules extract, are 1-year-old herbs belonging to the Lamiaceae family (Labiatae), and are known to be effective in anti-inflammatory, anti-allergic, anti-asthma, and antioxidant activities in modern medicine.

본 발명의 바람직한 일 실시예에 의하면, 상기 자소엽 추출물은 천연추출복합물 총 중량 대비 3.0 내지 10.0중량%로 함유될 수 있다. 상기 자소엽 추출물이 10.0중량%를 초과할 경우 자소엽이 지닌 한방작용은 충분히 나타나나 필요 이상이 양이 첨가되어 비경제적이고, 상기 자소엽 추출물이 3.0중량% 미만이면 항염증 등의 효과가 미미하다.According to a preferred embodiment of the present invention, the perilla leaf extract may be contained in an amount of 3.0 to 10.0% by weight based on the total weight of the natural extract complex. If the perilla leaf extract exceeds 10.0% by weight, the herbal action of perilla leaf is sufficiently exhibited, but it is uneconomical because more than necessary amount is added, and if the perilla leaf extract is less than 3.0% by weight, the effect such as anti-inflammatory is insignificant. .

상기 폴리아크릴산나트륨은 아크릴산중합물의 나트륨염으로서, 친수성 및 흡습성이 큰 특성을 나타내며 피막형성제, 피부컨디셔닝제, 유연제, 흡수제 등으로도 활용된다.The sodium polyacrylate is a sodium salt of an acrylic acid polymer, exhibits high hydrophilicity and hygroscopic properties, and is also used as a film forming agent, skin conditioning agent, softener, absorbent, and the like.

본 발명의 바람직한 일 실시예에 따르면, 상기 폴리아크릴산나트륨은 조성물 총 중량 대비 0.1 내지 0.5중량%로 함유된다. 상기 폴리아크릴산나트륨이 0.1중량% 미만으로 함유되면 친수성, 흡습성과 같은 기능 발휘가 미미하고, 0.5중량%를 초과하여 함유되면 물성 변화(고형화)가 두드러지게 나타날 수 있다.According to a preferred embodiment of the present invention, the sodium polyacrylate is contained in an amount of 0.1 to 0.5% by weight based on the total weight of the composition. When the sodium polyacrylate is contained in an amount of less than 0.1% by weight, functions such as hydrophilicity and hygroscopicity are insignificant, and when it is contained in an amount exceeding 0.5% by weight, a change in physical properties (solidification) may be noticeable.

본 발명의 추가 실시예에 있어서, 상기 구강점막부착형 필름 조성물은, 화장품학적으로 허용 가능한 화장품 보조제, 약제학적으로 허용 가능한 약학 보조제, 식품학적으로 허용 가능한 식품 보조제, 생물학적 활성 화합물, 흡수성 물질, 퍼스널 케어 화합물, 활성 성분, 미용 보조제 중 어느 하나 또는 이들의 조합을 더 포함하여 조성될 수 있다.In a further embodiment of the present invention, the oral mucosa-attached film composition is a cosmetically acceptable cosmetic adjuvant, a pharmaceutically acceptable pharmaceutical adjuvant, a food pharmaceutically acceptable food adjuvant, a biologically active compound, an absorbent substance, and a personal Any one of a care compound, an active ingredient, a cosmetic adjuvant, or a combination thereof may be further included.

한편, 상술한 바와 같은 성분들로 구성된 본 발명의 구강점막부착형 필름 조성물은 성형, 가공 등의 처리를 통하여 필름형으로 제조된다. 이때, 제조된 필름의 두께는 10 - 500㎛인 것이 바람직하다. 이는 상기 구강점막부착형 필름의 두께가 10㎛ 미만일 경우 구강점막에 부착이 용이하지 않고, 반대로 상기 구강점막부착형 필름의 두께가 500㎛를 초과할 경우 체내로의 흡수가 용이하게 이루어지지 않기 때문이다.On the other hand, the oral mucosa-attached film composition of the present invention composed of the above-described components is manufactured in a film form through treatments such as molding and processing. At this time, the thickness of the prepared film is preferably 10-500㎛. This is because when the thickness of the oral mucosa-attached film is less than 10 μm, it is not easy to adhere to the oral mucosa, and on the contrary, when the thickness of the oral mucosa-attached film exceeds 500 μm, absorption into the body is not easily achieved. to be.

이하, 실시예 및 실험예를 통하여 본 발명을 더욱 구체적으로 설명한다.Hereinafter, the present invention will be described in more detail through Examples and Experimental Examples.

[실시예] 구강점막부착형 필름 제조[Example] Oral mucosa adhesive film production

저분자 콜라겐 펩타이드(low-molecular weight collagen peptide) 10.5중량%, 엘라스틴 펩타이드(elastin peptide) 0.5중량%, 플루란(pullulan) 52.0중량%, 변성전분(modified starch) 12.5중량%, 글리세린(glycerin) 12.0중량%, 카라기난(carrageenan) 1.0중량%, 감미료 10.0중량%, 비타민나무 열매 추출물, 블랙베리 잎 추출물 및 자소엽 추출물로 구성된 천연추출복합물 1.0중량%, 폴리아크릴산나트륨(sodium polyacrylate) 0.5중량%를 혼합한 다음, 구강점막에 부착할 수 있는 필름 형태로, 본 발명에 따른 구강점막부착형 필름을 제조하였고, 제조된 필름을 실험의 용이성을 위해 가로 2.5㎝, 세로 2.5㎝의 크기로 복수개 절단하였다.Low-molecular weight collagen peptide 10.5% by weight, elastin peptide 0.5% by weight, flulan 52.0% by weight, modified starch 12.5% by weight, glycerin 12.0% by weight %, carrageenan (carrageenan) 1.0% by weight, sweetener 10.0% by weight, vitamin tree fruit extract, blackberry leaf extract and perilla leaf extract 1.0% by weight of a natural extract composition consisting of a mixture of 0.5% by weight of sodium polyacrylate (sodium polyacrylate) Next, in the form of a film that can be attached to the oral mucosa, an oral mucosa-attached film according to the present invention was prepared, and a plurality of the prepared films were cut into a size of 2.5 cm in width and 2.5 cm in length for ease of experimentation.

[실험예 1] 3D 구강점막세포를 이용한 저분자 콜라겐 투과율 평가[Experimental Example 1] Evaluation of low molecular weight collagen permeability using 3D oral mucosal cells

1. 구강점막세포에 투과된 콜라겐 양 측정1. Measurement of the amount of collagen permeated to the oral mucosa cells

구강점막세포에 투과된 콜라겐 양을 측정하기 위하여 BCA Assay법을 이용하였다. 3D 구강점막세포(Epioral, MatTek)의 Cell Culture Insert에 Donor Solution(PBS에 희석한 콜라겐)을 넣고 1시간과 2시간 후 Receiver Solution을 회수하여 BCA Assay법을 이용하여 투과된 콜라겐 양을 측정하였다. 콜라겐 양은 표준 용액으로부터 산출된 표준곡선으로부터 계산되었다.In order to measure the amount of collagen permeated to the oral mucosa cells, the BCA Assay method was used. Donor Solution (collagen diluted in PBS) was added to the cell culture insert of 3D oral mucosal cells (Epioral, MatTek), and the Receiver Solution was recovered after 1 hour and 2 hours, and the amount of permeated collagen was measured using the BCA Assay method. The amount of collagen was calculated from a standard curve calculated from a standard solution.

도 1에 구강점막세포에 투과된 콜라겐 양을 정량화하여 나타내었다. 상기 도 1을 참고하여 실험결과를 설명하면, 시간이 경과함에 따라 3D 구강점막세포에 투과된 콜라겐의 양은 증가되며, 고분자 콜라겐에 비해 저분자 콜라겐의 투과량이 유의적으로 높게 관찰되는 것으로 보아, 구강점막세포에서 고분자 콜라겐 보다 저분자 콜라겐의 흡수가 더 빠르게 일어남을 확인할 수 있다.In Figure 1, the amount of collagen permeated to the oral mucosa cells was quantified and shown. Referring to Fig. 1 above, the experimental results are described, as the amount of collagen permeated to the 3D oral mucosa cells increases as time elapses, and the amount of low molecular collagen permeation is significantly higher than that of high molecular collagen. It can be seen that the absorption of low-molecular collagen occurs faster than that of high-molecular collagen in cells.

2. 구강점막세포에 콜라겐 투과도 확인2. Confirmation of collagen permeability to oral mucosa cells

구강점막세포에 콜라겐 투과도를 확인하기 위하여 형광 표지된 콜라겐을 이용하였다. 3D 구강점막세포(Epioral, MatTek)의 Cell Culture Insert에 Donor Solution(PBS에 희석한 FITC-Collagen)을 넣고 1시간 후 4% PFA용액을 이용하여 고정시켰다. 이후 동결절편을 제작하고 형광현미경을 이용하여 3D 구강점막세포를 관찰하였다.Fluorescently labeled collagen was used to check the collagen permeability to oral mucosal cells. Donor Solution (FITC-Collagen diluted in PBS) was added to the Cell Culture Insert of 3D oral mucosal cells (Epioral, MatTek), and after 1 hour, it was fixed using 4% PFA solution. Thereafter, frozen sections were prepared and 3D oral mucosal cells were observed using a fluorescence microscope.

도 2는 구강점막세포에 콜라겐 투과도를 형광현미경으로 관찰한 사진을 나타낸 것이다. 상기 도 2를 참조하여 실험결과를 설명하면, 동일한 시간동안 형광 표지된 콜라겐을 처리하였을 때, 고분자 콜라겐은 구강점막 위쪽 부분에 주로 분포되는 반면에 저분자 콜라겐은 구강점막 위쪽부터 아래쪽까지 투과되는 것으로 보아, 저분자 콜라겐의 흡수가 더 용이함을 확인할 수 있다.Figure 2 shows a picture of the collagen permeability observed with a fluorescence microscope in the oral mucosal cells. Referring to FIG. 2, the experimental results are described as above, when the fluorescently-labeled collagen is treated for the same period of time, the high molecular collagen is mainly distributed in the upper part of the oral mucosa, whereas the low-molecular collagen is seen to be transmitted from the top to the bottom of the oral mucosa. , It can be seen that absorption of low-molecular collagen is easier.

[실험예 2] 구강점막부착형 필름의 주름개선 효과 확인[Experimental Example 2] Confirmation of wrinkle improvement effect of oral mucosa-attached film

1. Elastase 활성 억제능 평가1. Elastase activity inhibition ability evaluation

본 발명의 구강점막부착형 필름의 주름개선 효과를 평가하기 위해 Elastase 활성 억제능을 평가하였다. 0.1M Tris-HCl buffer (pH 8.0)에 농도별로 희석한 시료 220㎕와 2㎎/㎖ N-succinyl-Ala-Ala-Ala-ρ-nitroanilide 20㎕를 첨가하여 25℃ 조건에서 10분간 반응시켰다. 1㎍/㎖의 porcine pancreatic elastase (PPE) 20㎕를 첨가하여 25℃ 조건에서 20분간 반응시킨 다음 얼음위에서 반응을 종결시킨 후 microplate reader를 이용하여 405㎚에서 흡광도를 측정하였으며, Elastase 억제능은 시료 처리구와 무처리구의 흡광도 감소율로 나타내었다.In order to evaluate the anti-wrinkle effect of the oral mucosa-attached film of the present invention, the ability to inhibit Elastase activity was evaluated. 220 µl of a sample diluted by concentration in 0.1M Tris-HCl buffer (pH 8.0) and 20 µl of 2 mg/ml N-succinyl-Ala-Ala-Ala-ρ-nitroanilide were added and reacted at 25° C. for 10 minutes. After adding 20 µl of 1µg/ml porcine pancreatic elastase (PPE) and reacting for 20 minutes at 25℃, the reaction was terminated on ice, and the absorbance was measured at 405nm using a microplate reader. It was expressed as the absorbance reduction rate of the and untreated groups.

도 3에 주름개선 효과를 평가하기 위한 Elastase 활성 억제능 결과를 나타내었다. 도 3에 나타난 바와 같이, 구강점막부착형 필름의 처리는 농도 의존적인 Elastase 활성 억제능이 관찰되는 것을 확인할 수 있다. 이 같은 결과로 보아 본 발명에 따른 저분자 콜라겐 펩타이드를 포함하는 구강점막부착형 필름은 주름개선에 유의한 효과가 있다는 결론을 도출할 수 있다.Figure 3 shows the results of the Elastase activity inhibitory ability to evaluate the wrinkle improvement effect. As shown in Figure 3, it can be seen that the treatment of the oral mucosa-attached film is a concentration-dependent Elastase activity inhibitory ability is observed. From these results, it can be concluded that the oral mucosa-attached film comprising the low-molecular collagen peptide according to the present invention has a significant effect on wrinkle improvement.

2. Collagenase 활성 억제능 평가2. Evaluation of inhibitory ability of collagenase activity

저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름의 주름개선 효과를 평가하기 위해 Collagenase 활성 억제능을 확인하였다. 시료를 농도별로 희석한 후 Collagenase Activity Assay kit(Abcam)을 사용하여 측정하였다. Assay buffer 88㎕에 농도별로 희석한 시료 2㎕와 Collagenase 10㎕를 추가한 후 100㎕의 Collagenase Reaction Mix를 첨가하여 반응시킨 후 microplate reader를 이용하여 345㎚에서 흡광도를 측정하였으며, Collagenase 억제능은 시료 처리구와 무처리구의 흡광도 감소율로 나타내었다.In order to evaluate the anti-wrinkle effect of the oral mucosa-attached film containing a low-molecular collagen peptide and a natural extract complex, the ability to inhibit collagenase activity was confirmed. After diluting the sample by concentration, it was measured using a Collagenase Activity Assay kit (Abcam). After adding 2 µl of sample diluted by concentration and 10 µl of Collagenase to 88 µl of assay buffer, 100 µl of Collagenase Reaction Mix was added to react, and absorbance was measured at 345 nm using a microplate reader. It was expressed as the absorbance reduction rate of the and untreated groups.

도 4에 본 발명의 구강점막부착형 필름의 주름개선 효과를 평가하기 위한 Collagenase 활성 억제능 결과를 나타내었다.Figure 4 shows the results of the collagenase activity inhibitory ability to evaluate the wrinkle improvement effect of the oral mucosa-attached film of the present invention.

도 4에 나타난 바와 같이, 구강점막부착형 필름의 처리는 농도 의존적인 Collagenase 활성 억제능이 관찰되었으며, 이 같은 결과에 비추어 본 발명에 따른 구강점막부착형 필름은 주름개선에 유의한 효과가 있다는 결론을 도출할 수 있다.As shown in Fig. 4, the treatment of the oral mucosa-attached film was observed to have a concentration-dependent collagenase activity inhibitory ability, and in view of these results, it was concluded that the oral mucosa-attached film according to the present invention had a significant effect on wrinkle improvement. Can be derived.

3. Type-1 procollagen 합성 촉진 활성 평가3. Evaluation of Type-1 procollagen synthesis promotion activity

저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름의 주름개선 효과를 평가하기 위해 Type-1 procollagen 합성 촉진 활성을 확인하였다. HDF 세포(Human Dermal Fibroblast cell)를 10% FBS가 들어간 DMEM 세포배양액에 37℃ 5% CO2 조건에서 배양한 후 well당 1×104 cell이 되도록 96-well plate에 깔아준 후, 12시간 동안 배양하면서 세포를 완전히 부착시켰다. 각 well의 세포들을 무혈청 DMEM 배양액으로 세척한 다음 각 well에 시료를 최종농도 62.5, 125, 250, 500, 1000, 2000㎍/㎖가 되도록 처리한 후 48시간 동안 배양하였다. 배양액을 수집하여 Procollagen type 1 C-peptide assay kit(Takara Bio Inc.)를 사용하여 콜라겐 함량을 측정하였으며, 이때 콜라겐의 농도는 kit에 포함되어 있는 표준 용액으로부터 산출된 표준곡선으로부터 계산되었다.In order to evaluate the anti-wrinkle effect of the oral mucosa-attached film containing a low-molecular collagen peptide and a natural extract complex, the activity of promoting Type-1 procollagen synthesis was confirmed. HDF cells (Human Dermal Fibroblast cells) were cultured in DMEM cell culture solution containing 10% FBS at 37°C and 5% CO 2 conditions, and then spread on a 96-well plate to become 1×10 4 cells per well, and then for 12 hours. The cells were completely attached while culturing. Cells in each well were washed with serum-free DMEM culture, and then the samples were treated in each well to a final concentration of 62.5, 125, 250, 500, 1000, and 2000 µg/ml, followed by incubation for 48 hours. The culture medium was collected and the collagen content was measured using a Procollagen type 1 C-peptide assay kit (Takara Bio Inc.), and the collagen concentration was calculated from a standard curve calculated from the standard solution included in the kit.

도 5에 본 발명의 구강점막부착형 필름의 주름개선 효과를 평가하기 위한 Type-1 procollagen 합성 촉진 활성 평가 결과를 나타내었다.Fig. 5 shows the results of evaluating Type-1 procollagen synthesis promoting activity for evaluating the wrinkle improvement effect of the oral mucosa-attached film of the present invention.

도 5를 참조하여 실험결과를 설명하면, 구강점막부착형 필름의 처리는 농도 의존적인 Type-1 procollagen 합성 촉진이 관찰되었고, 이 같은 결과는 본 발명에 따른 저분자 콜라겐 펩타이드를 포함하는 구강점막부착형 필름이 주름개선에 유의한 효과가 있다는 결론을 도출할 수 있다.Referring to Figure 5 to explain the experimental results, the treatment of the oral mucosa-attached film was observed to promote concentration-dependent Type-1 procollagen synthesis, and this result is the oral mucosa-attached type containing the low-molecular collagen peptide according to the present invention. It can be concluded that the film has a significant effect on wrinkle improvement.

[실험예 3] 구강점막부착형 필름의 항산화 효과[Experimental Example 3] Antioxidant Effect of Oral Mucosa Attached Film

저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름의 항산화 효과를 평가하기 위하여 DPPH의 자유라디칼 소거능을 확인하였다. 메탄올에 용해한 200μM DPPH(1,1-diphenyl-2-picryl hydrazyl) 200㎕에 125, 250, 500, 1000, 2000㎍/㎖로 희석한 시료를 50㎕ 첨가하여 37℃에서 30분 동안 반응시킨 다음 microplate reader를 이용하여 405㎚에서 흡광도를 측정하였다. DPPH의 자유라디칼 소거능은 시료 처리군과 무처리군의 흡광도 감소율로 나타내었다.In order to evaluate the antioxidant effect of the oral mucosa-attached film containing a low molecular weight collagen peptide and a natural extract complex, the free radical scavenging ability of DPPH was confirmed. To 200 μl of 200 μM DPPH (1,1-diphenyl-2-picryl hydrazyl) dissolved in methanol, 50 μl of samples diluted with 125, 250, 500, 1000, and 2000 μg/ml were added and reacted at 37° C. for 30 minutes. Absorbance was measured at 405 nm using a microplate reader. The free radical scavenging ability of DPPH was expressed as the rate of decrease in absorbance of the sample-treated group and the non-treated group.

도 6에 본 발명의 구강점막필름형 필름의 항산화 효과를 나타내기 위한 DPPH의 자유라디칼 소거능을 나타내었다.Figure 6 shows the free radical scavenging ability of DPPH for showing the antioxidant effect of the oral mucosa film-type film of the present invention.

도 6을 참조하여 실험결과를 설명하면, 저분자 펩타이드를 주성분으로 하는 구강점막필름의 농도별 처리는 DPPH의 자유라디칼 소거능을 증가시켜주는 것으로 관찰되었고, 이 같은 결과에 비추어 본 발명에 따른 구강점막부착형 필름이 항산화에 유의한 효과가 있다는 결론을 도출할 수 있다.Referring to Figure 6 to explain the experimental results, it was observed that the concentration-specific treatment of the oral mucosa film containing a low molecular weight peptide as a main component increases the free radical scavenging ability of DPPH, and in light of this result, the oral mucosa adhesion according to the present invention It can be concluded that the type film has a significant effect on antioxidants.

[실험예 4] 구강점막부착형 필름의 미백 효과[Experimental Example 4] Whitening effect of oral mucosa-attached film

저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름의 미백 효과를 평가하기 위하여 Tyrosinase 활성 억제능을 확인하였다. 0.1M phosphate buffer(pH 6.5) 50㎕에 시료 50㎕와 100unit/㎖ Tyrosinase 50㎕를 첨가하여 상온에서 5분간 반응시켰다. 1mM L-DOPA 100㎕를 첨가하여 37℃에서 30분간 반응시킨 후 microplate reader를 이용하여 475㎚에서 흡광도를 측정하였으며 Tyrosinase 저해활성은 시료 처리구와 무처리구의 흡광도 감소율로 나타내었다.In order to evaluate the whitening effect of the oral mucosa-attached film containing a low molecular weight collagen peptide and a natural extract complex, the ability to inhibit tyrosinase activity was confirmed. 50 µl of a sample and 50 µl of 100 unit/ml Tyrosinase were added to 50 µl of 0.1M phosphate buffer (pH 6.5), and reacted at room temperature for 5 minutes. After adding 100 µl of 1mM L-DOPA and reacting for 30 minutes at 37°C, absorbance was measured at 475 nm using a microplate reader, and the tyrosinase inhibitory activity was expressed as the decrease in absorbance of the sample treated and untreated groups.

도 7에 본 발명의 구강점막부착형 필름의 미백효과를 나타내기 위한 Tyrosinase 활성 억제능을 나타내었다.Figure 7 shows the ability to inhibit Tyrosinase activity for showing the whitening effect of the oral mucosa-attached film of the present invention.

도 7을 참조하여 실험결과를 설명하면, 구강점막부착형 필름의 처리는 농도 의존적인 Tyrosinase 활성 억제능이 관찰되었고, 이 같은 결과에 비추어 본 발명에 따른 구강점막부착형 필름은 미백에 유의한 효과가 있다는 결론을 도출할 수 있다.Referring to Figure 7 to describe the experimental results, the treatment of the oral mucosa-attached film was observed to have a concentration-dependent inhibitory ability to inhibit Tyrosinase activity, and in view of these results, the oral mucosa-attached film according to the present invention had a significant effect on whitening. It can be concluded that there is.

[실험예 5] 구강점막부착형 필름의 피부 주름 개선 효과[Experimental Example 5] Skin wrinkle improvement effect of oral mucosa-attached film

사람에서의 피부 주름 개선 효과를 평가하기 위하여 전문가에 의한 눈가주름 육안평가(8 point scale)를 진행하였다. 평균연령 47세(46.80±3.32)의 건강한 여성 20명에게 1일 2개의 필름을 구강 안쪽 볼에 부착하여 12주간 사용하게 한 후, 눈가주름 육안평가를 진행하였다. 눈가주름 정도에 따라 0부터 7까지의 점수를 부여하였고, 구체적인 평가 기준은 하기 표 1에 나타내었다.In order to evaluate the effect of improving skin wrinkles in humans, an expert's visual evaluation (8 point scale) was conducted. Twenty healthy women with an average age of 47 years (46.80±3.32) were allowed to use two films a day on the inner cheeks of the oral cavity for 12 weeks, and then visually evaluated the wrinkles of the eyes. Scores from 0 to 7 were given according to the degree of wrinkles, and specific evaluation criteria are shown in Table 1 below.

RatingRating DescriptionDescription 00 NoneNone 1One None / MildNone / Mild 22 MildMild 33 Mild / ModerateMild / Moderate 44 ModerateModerate 55 Moderate /SevereModerate /Severe 66 SevereSevere 77 Very SevereVery Severe

도 8은 본 발명에 따른 구강점막부착형 필름의 피부 주름 개선 효과를 평가한 그래프이다. 도 8을 참조하여 실험결과를 설명하면, 평균연령 47세(46.80±3.32)의 건강한 여성 20명에게 1일 2개의 필름을 구강 안쪽 볼에 부착하여 12주간 사용하게 한 후, 피부주름을 살펴본 결과 눈가에 주름이 호전되는 것을 육안으로 관찰할 수 있었으며, 이 같은 결과에 비추어 볼 때, 본 발명에 따른 구강점막부착형 필름은 피부 주름 개선에 유의한 효과가 있음을 확인할 수 있다.8 is a graph evaluating the effect of improving skin wrinkles of the oral mucosa-attached film according to the present invention. Referring to FIG. 8, the experimental results will be described with reference to FIG. 8, after 20 healthy women with an average age of 47 years (46.80±3.32) were allowed to use two films a day on the inner cheeks of the oral cavity for 12 weeks, and the skin wrinkles were examined. Improvement of wrinkles around the eyes could be observed with the naked eye, and in light of these results, it can be seen that the oral mucosa-attached film according to the present invention has a significant effect on improving skin wrinkles.

[실험예 6] 구강점막부착형 필름의 피부 탄력 향상 효과[Experimental Example 6] Effect of improving skin elasticity of oral mucosa-attached film

사람에서의 피부 탄력 향상 효과를 평가하기 위하여 피부탄력 측정기를 이용하여 피부탄력을 측정하였다. 평균연령 47세(46.80±3.32)의 건강한 여성 20명에게 1일 2개의 필름을 구강 안쪽 볼에 부착하여 12주간 사용하게 한 후, Reviscometer(MAP5)를 이용하여 진피 내 탄력섬유 등의 방향이나 미세한 피부표면의 변화를 측정하였다.In order to evaluate the effect of improving skin elasticity in humans, skin elasticity was measured using a skin elasticity meter. Twenty healthy women with an average age of 47 years (46.80±3.32) attach two films a day to the inner cheeks of the oral cavity and use them for 12 weeks. Changes in the skin surface were measured.

도 9는 본 발명에 따른 구강점막부착형 필름의 피부 탄력 향상 효과를 평가한 결과를 나타낸 그래프로써, 도 9를 참조하여 실험결과를 설명하면, 평균연령 47세(46.80±3.32)의 건강한 여성 20명에게 1일 2개의 필름을 구강 안쪽 볼에 부착하여 12주간 사용하게 한 후, Reviscometer를 이용하여 피부 탄력을 측정하였고, 그 결과 12주째 통계학적으로 유의한 피부 탄력효과가 관찰되는 것으로 보아, 본 발명에 따른 구강점막부착형 필름은 피부 탄력 향상에 유효함을 확인할 수 있다.FIG. 9 is a graph showing the results of evaluating the effect of improving skin elasticity of the oral mucosa-attached film according to the present invention. Referring to FIG. 9, the experimental results will be described. After attaching two films a day to the cheeks inside the oral cavity to use for 12 weeks, the skin elasticity was measured using a Reviscometer. As a result, statistically significant skin elasticity effect was observed at 12 weeks. It can be seen that the oral mucosa-attached film according to the invention is effective in improving skin elasticity.

Claims (7)

피부노화 방지, 주름개선, 피부탄력강화, 미백 기능을 발휘하는 분자량 1×104 dalton 이하의 저분자 콜라겐 펩타이드(low-molecular weight collagen peptide) 1.5 - 22.0중량%,
수분보유량, 표피유연성 증대 및 피부탄력 개선 기능을 발휘하는 엘라스틴 펩타이드(elastin peptide) 0.1 - 1.0중량%,
접착성과 조막성을 갖는 수용성 플루란(pullulan) 50.0 - 54.0중량%,
본래의 구조나 물성을 변형시킨 산처리화 변성전분, 하이드록시프로필화 변성전분, α화 변성전분 중 어느 하나의 변성전분(modified starch) 10.0 - 13.0중량%,
공기 중의 수분을 흡수하여 보습제로의 기능을 부여하 글리세린(glycerin) 10.0 - 13.0중량%,
필름의 인장강도를 증대시키기 위해 함유되는 카라기난(carrageenan) 0.6 - 2.0중량%,
구강 내에 적용하더라도 쓴맛을 차폐하는 아스파탐 6.2 - 13.5중량%,
항염증, 항산화 작용을 하는 비타민나무 열매 추출물 15.0 - 32.0중량%, 블랙베리 잎 추출물 65.0 - 75.0중량%, 자소엽 추출물 3.0 - 10.0중량%로 구성되는 천연추출복합물 1.0 - 1.5중량%,
친수성 및 흡습성 기능을 발휘하는 폴리아크릴산나트륨(sodium polyacrylate) 0.1 - 0.5중량%; 로 구성된 것을 특징으로 하는 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물.
Low-molecular weight collagen peptide 1.5-22.0% by weight, with a molecular weight of 1×10 4 dalton or less, which exhibits skin aging prevention, wrinkle improvement, skin elasticity, and whitening functions,
0.1-1.0% by weight of elastin peptide that exhibits the function of increasing moisture retention, epidermal flexibility and improving skin elasticity,
50.0-54.0% by weight of water-soluble flulan having adhesiveness and film-forming properties,
10.0-13.0% by weight of modified starch of any one of acid-treated modified starch, hydroxypropylated modified starch, and α-modified starch with modified original structure or physical properties,
Glycerin 10.0-13.0% by weight, which absorbs moisture in the air and imparts the function as a moisturizing agent,
0.6-2.0% by weight of carrageenan contained in order to increase the tensile strength of the film,
6.2-13.5% by weight of aspartame, which masks the bitter taste even when applied in the oral cavity,
Natural extract complex consisting of 15.0-32.0% by weight of vitamin tree fruit extract with anti-inflammatory and antioxidant activity, 65.0-75.0% by weight of blackberry leaf extract, 3.0-10.0% by weight of perilla leaf extract, 1.0-1.5% by weight,
0.1-0.5% by weight of sodium polyacrylate exhibiting hydrophilic and hygroscopic functions; Oral mucosa-attached film composition comprising a low-molecular collagen peptide and a natural extract complex, characterized in that consisting of.
삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 상기 제1항에 따른 조성물을 이용하여 제조한 분자량 1×104 dalton 이하의 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름.An oral mucosa-attached film comprising a low-molecular collagen peptide having a molecular weight of 1×10 4 dalton or less and a natural extract complex prepared by using the composition according to claim 1.
KR1020190087753A 2019-07-19 2019-07-19 An oral mucoadhesive film composition comprising a low molecular weight collagen peptide and a natural extract compound and an oral mucoadhesive film prepared using the same KR102221453B1 (en)

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