KR20240041381A - Composition for the prevention or treatment of periodontal disease - Google Patents
Composition for the prevention or treatment of periodontal disease Download PDFInfo
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- KR20240041381A KR20240041381A KR1020220119089A KR20220119089A KR20240041381A KR 20240041381 A KR20240041381 A KR 20240041381A KR 1020220119089 A KR1020220119089 A KR 1020220119089A KR 20220119089 A KR20220119089 A KR 20220119089A KR 20240041381 A KR20240041381 A KR 20240041381A
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- South Korea
- Prior art keywords
- periodontal disease
- alveolar bone
- preventing
- composition
- present
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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- A—HUMAN NECESSITIES
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/312—Foods, ingredients or supplements having a functional effect on health having an effect on dental health
Landscapes
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- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Food Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
Abstract
본 발명은 치주 질환 예방 또는 치료용 조성물에 관한 것으로, 보다 구체적으로 서열번호 1의 아미노산 서열로 이루어진 SDF1δ 유래 펩타이드 S10을 이용하여 치주염을 유발하는 다양한 구강 내 세균을 억제함으로써 염증을 완화하고 치조골 형성을 활성화시키는 효과를 갖는 치주 질환 예방 또는 치료용 조성물을 제공한다.The present invention relates to a composition for preventing or treating periodontal disease, and more specifically, to relieve inflammation and promote alveolar bone formation by suppressing various oral bacteria that cause periodontitis using SDF1δ-derived peptide S10, which consists of the amino acid sequence of SEQ ID NO: 1. Provided is a composition for preventing or treating periodontal disease that has an activating effect.
Description
본 발명은 치주 질환 예방 또는 치료용 조성물에 관한 것으로, 보다 구체적으로 SDF1δ 유래 펩타이드 S10을 이용하여 치주염을 유발하는 다양한 균을 억제함으로써 염증을 완화하고 치조골 형성을 활성화시키는 효과를 갖는 치주 질환 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating periodontal disease, and more specifically, to preventing or treating periodontal disease, which has the effect of alleviating inflammation and activating alveolar bone formation by suppressing various bacteria that cause periodontitis using SDF1δ-derived peptide S10. It relates to a composition for use.
치아는 구조상 인체내 가장 단단한 경조직으로서 치조골(alveolar bone)에 지지되고 있다. 치조골은 악골의 기저골에 단단히 부착되어 있고, 치근에 바로 인접한 2-3 mm 부분을 치주골이라 칭하기도 하나, 통상 치조골이라함은 상기 치주골을 포함한 경조직 모두를 지칭한다. 치조골은 연령이 증가함에 따라 점차 낮아지면서 치아 뿌리가 노출되는 현상을 보이기도 한다. 또한, 치아를 상실하면 치조골도 점차 소실되는 상관관계를 갖는다. 이러한 구강내 치조골은 평균 0.2mm 정도 두께의 치주인대(periodontal ligament)라는 미분화 간엽세포가 존재하는 층에 의해서 치아를 부착하고 지지하면서, 치아가 음식의 저작시 완충 작용할 수 있도록 치조골에 힘을 분산시키기도 하며, 치아의 감각을 치주인대를 통하여 치조골에 전달하기도 한다. 또한, 치주인대는 미분화 간엽세포가 존재하는 층으로 계속하여 전체섬유의 구조와 기능을 소실시키지 않고, 골개조를 계속하면서, 압력에 적응하도록 구조화되어있다. 치주인대 내 미분화 간엽세포는 인접조직으로 이동하는데, 치조골 쪽으로 이동하여 치조골개조를 담당하며, 다른 한편으로는 치아 쪽으로 이동하여 교원섬유를 만들어내어 치아를 더욱 단단히 붙들 수 있도록 지속적으로 개조된다. 이러한 치아는 치조골에서 조골세포에 의한 골형성과 파골세포에 의한 골흡수가 함께 일어나, 지속적인 리모델링(remodeling)을 통해 균형을 유지하고 있다.Structurally, teeth are the hardest hard tissue in the human body and are supported by alveolar bone. The alveolar bone is firmly attached to the basal bone of the jaw bone, and the 2-3 mm part immediately adjacent to the tooth root is sometimes called periodontal bone. However, the term alveolar bone usually refers to all hard tissues including the periodontal bone. As the age increases, the alveolar bone gradually decreases, exposing the tooth roots. Additionally, when teeth are lost, alveolar bone is gradually lost. This intraoral alveolar bone attaches and supports the teeth by a layer of undifferentiated mesenchymal cells called the periodontal ligament, which is about 0.2 mm thick on average, and also distributes force to the alveolar bone so that the teeth can act as a cushion when chewing food. In addition, the sensation of teeth is transmitted to the alveolar bone through the periodontal ligament. In addition, the periodontal ligament is a layer in which undifferentiated mesenchymal cells exist and is structured to adapt to pressure while continuing bone remodeling without losing the structure and function of the entire fiber. Undifferentiated mesenchymal cells within the periodontal ligament move to adjacent tissues. They move toward the alveolar bone and are responsible for alveolar bone remodeling. On the other hand, they move toward the teeth and produce collagen fibers, which are continuously remodeled to hold the teeth more tightly. In these teeth, bone formation by osteoblasts and bone resorption by osteoclasts occur together in the alveolar bone, maintaining balance through continuous remodeling.
치주 질환(Periodontal disease)은 치아를 지지하는 치은과 치골에 영향을 미치는 질환으로 치은염(gingivitis)과 치주염(periodontitis) 등을 포함한다. 치은염은 잇몸의 연조직에 염증이 생기는 초기 치주 질환으로 비교적 증상이 가볍고 회복이 가역적인 상태이다. 치주염은 치은염이 치료되지 않고 염증이 잇몸과 치골 주변까지 진행된 경우로 세균의 독소에 의해 자극된 만성 염증반응이 진전되면 잇몸과 치아 사이에서 분리되어 감염된 치주낭(periodontal pocket)이 형성되고, 치주염이 심할수록 치주낭의 깊이가 깊어져서 결국, 치주인대에 염증이 생기게 되고 골소실이 일어난다. 또한, 치조골에서 조골세포에 의한 골형성과 파골세포에 의한 골흡수의 대사가 여러 가지 요인에 의해 골량이 한계 이하로 감소하면 치조골다공증과 같은 치조골형성장애가 발생한다.Periodontal disease is a disease that affects the gingiva and pubic bone that support the teeth and includes gingivitis and periodontitis. Gingivitis is an early periodontal disease in which the soft tissue of the gums becomes inflamed. The symptoms are relatively mild and recovery is reversible. Periodontitis is when gingivitis is not treated and the inflammation progresses to the gums and around the pubic bone. When the chronic inflammatory response stimulated by bacterial toxins progresses, the gums and teeth become separated and an infected periodontal pocket is formed, and periodontitis can become severe. As the periodontal pockets become deeper, the periodontal ligament becomes inflamed and bone loss occurs. In addition, when the metabolism of bone formation by osteoblasts and bone resorption by osteoclasts in the alveolar bone decreases below the limit due to various factors, alveolar bone formation disorders such as alveolar osteoporosis occur.
치주 질환의 치료는 환자의 개선된 구강위생의 확립, 비외과적 혹은 외과적인 치석제거술, 치근활택술, 치은소파술과 신부착을 응용한 치주 조직의 재생술들이 이용되어져 왔다. 그러나 이런 외과적인 치료 방법은 치료가 번거로우며 효과적인 치료가 어렵고 또한 병의 예방보다는 병이 어느 정도 진행되었을 경우 행하는 치료에 국한되어 있어, 치료를 하지 않을 경우 대부분이 만성으로 진행되는 경우가 대부분이다. Treatment of periodontal disease has been used to establish the patient's improved oral hygiene, non-surgical or surgical calculus removal, root planing, gingival curettage, and periodontal tissue regeneration using new attachment. However, these surgical treatment methods are cumbersome and difficult to treat effectively, and are limited to treatment when the disease has progressed to a certain degree rather than prevention of the disease. Therefore, if not treated, most cases progress to chronic disease.
또한, 부가적인 치료로 전신적인 항생제의 복용과 국소 서방형 제재가 사용되어 왔으나, 불필요한 부위에도 약물이 너무 많이 전달되어 그로 인한 부작용과 최근 사용되는 항생제에 대한 내성을 나타내는 치주 질환 균이 분리된 예가 보고되고 있어 심각한 문제점을 안고 있다. In addition, systemic antibiotics and topical sustained-release agents have been used as additional treatments, but too much medication is delivered to unnecessary areas, resulting in side effects, and there are examples of periodontal disease bacteria that have recently been isolated that show resistance to recently used antibiotics. It has been reported that it poses a serious problem.
게다가, 치주 질환은 일반적인 염증, 관절염 등과 다르게 치조골의 손실, 염증, 진지발리스와 같은 치주염균에 의한 복합적인 유발원인을 가지는 특징이 있어, 항균 및 항염증, 조골세포의 골세포로의 촉진 등의 복합적 치료 방법이 필요하나, 이러한 치료를 위한 약물 내지 치료법이 개발되어 있지 않다.In addition, periodontal disease, unlike general inflammation and arthritis, is characterized by complex causes such as loss of alveolar bone, inflammation, and periodontitis bacteria such as gingivalis, and has antibacterial and anti-inflammatory properties, promotion of osteoblasts into osteocytes, etc. Complex treatment methods are needed, but no drugs or treatments have been developed for such treatment.
따라서, 전술한 문제점을 보완하기 위해 본 발명가들은 치주 질환을 효과적으로 치료할 수 있는 약물 내지 치료제의 개발이 시급하다 인식하여, 본 발명을 완성하였다.Therefore, in order to supplement the above-mentioned problems, the present inventors recognized that it is urgent to develop a drug or therapeutic agent that can effectively treat periodontal disease, and completed the present invention.
본 발명의 목적은 SDF1δ 유래 펩타이드 S10을 이용하여 치주 질환을 유발하는 다양한 균을 억제함으로써 염증을 완화하고 치조골 형성을 활성화시키는 효과를 갖는 치주 질환 예방 및 치료용 조성물을 제공하는 것이다.The purpose of the present invention is to provide a composition for preventing and treating periodontal disease that has the effect of alleviating inflammation and activating alveolar bone formation by suppressing various bacteria that cause periodontal disease using SDF1δ-derived peptide S10.
본 발명의 다른 목적은 SDF1δ 유래 펩타이드 S10을 이용하여 치주 질환을 유발하는 다양한 균을 억제함으로써 염증을 완화하고 치조골 형성을 활성화시키는 효과를 갖는 치주 질환 예방 또는 개선을 위한 경구용 조성물을 제공하는 것이다.Another object of the present invention is to provide an oral composition for preventing or improving periodontal disease that has the effect of alleviating inflammation and activating alveolar bone formation by suppressing various bacteria that cause periodontal disease using SDF1δ-derived peptide S10.
본 발명의 또 다른 목적은 SDF1δ 유래 펩타이드 S10을 이용하여 치주 질환을 유발하는 다양한 균을 억제함으로써 염증을 완화하고 치조골 형성을 활성화시키는 효과를 갖는 치주 질환 예방 또는 개선을 위한 구강용 외용제 조성물을 제공하는 것이다.Another object of the present invention is to provide a composition for oral external application for preventing or improving periodontal disease, which has the effect of alleviating inflammation and activating alveolar bone formation by suppressing various bacteria that cause periodontal disease using SDF1δ-derived peptide S10. will be.
본 발명의 또 다른 목적은 SDF1δ 유래 펩타이드 S10을 이용하여 치주 질환을 유발하는 다양한 균을 억제함으로써 염증을 완화하고 치조골 형성을 활성화시키는 효과를 갖는 치주 질환 예방 또는 개선용 건강기능식품을 제공하는 것이다.Another object of the present invention is to provide a health functional food for preventing or improving periodontal disease that has the effect of alleviating inflammation and activating alveolar bone formation by suppressing various bacteria that cause periodontal disease using SDF1δ-derived peptide S10.
발명이 이루고자 하는 기술적 과제들은 이상에서 언급한 기술적 과제들로 제한되지 않으며, 언급되지 않은 또 다른 기술적 과제들은 본 발명의 기재로부터 당해 분야에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있다.The technical problems to be achieved by the invention are not limited to the technical problems mentioned above, and other technical problems not mentioned can be clearly understood by those skilled in the art from the description of the present invention.
상기 목적을 달성하기 위하여, 본 발명은 치주 질환 예방 또는 치료용 조성물 및 이의 용도를 제공한다.In order to achieve the above object, the present invention provides a composition for preventing or treating periodontal disease and its use.
이하, 본 명세서에 대하여 더욱 상세하게 설명한다.Hereinafter, this specification will be described in more detail.
본 발명은 서열번호 1의 아미노산 서열로 이루어진 펩타이드를 유효성분으로 포함하는, 치주 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating periodontal disease, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
본 발명에 있어서, 상기 치주 질환은 치은염(gingivitis), 치주염(periodontal inflammation), 치조골 파손(alveolar bone breakage) 및 치조골형성장애(alveolar bone osteodystrophy)로 이루어진 군으로부터 선택된 1종 이상일 수 있다.In the present invention, the periodontal disease may be one or more types selected from the group consisting of gingivitis, periodontitis, alveolar bone breakage, and alveolar bone osteodystrophy.
본 발명에 있어서, 상기 치조골형성장애는 치조골다공증(alveolar bone osteoporosis), 치조골연화증(alveolar bone osteomalacia) 및 치조골감소증(alveolar bone osteopenia)으로 이루어진 군으로부터 선택된 1종 이상일 수 있다.In the present invention, the alveolar bone dysplasia may be one or more types selected from the group consisting of alveolar bone osteoporosis, alveolar bone osteomalacia, and alveolar bone osteopenia.
본 발명에 있어서, 상기 펩타이드는 포르피로모나스 진지발리스(Porphyromonas gingivalis), 아그레가티박터 액티노마이세템코미탄스(Aggregatibacter actinomycetemcomitans), 퓨조박테리움 뉴클레아툼(Fusobacterium nucleatum), 스트렙토코쿠스 뮤탄스(Streptococcus mutans), 및 트레포네마 덴티콜라(Treponema denticola)로 이루어진 군에서 선택된 하나 이상의 발현을 억제할 수 있다.In the present invention, the peptide is Porphyromonas gingivalis , Aggregatibacter actinomycetemcomitans , Fusobacterium nucleatum , and Streptococcus mu. The expression of one or more selected from the group consisting of Streptococcus mutans and Treponema denticola can be suppressed.
또한, 본 발명은 서열번호 1의 아미노산 서열로 이루어진 펩타이드를 유효성분으로 포함하는, 치주 질환의 예방 또는 개선을 위한 경구용 조성물을 제공한다.In addition, the present invention provides an oral composition for preventing or improving periodontal disease, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
또한, 본 발명은 서열번호 1의 아미노산 서열로 이루어진 펩타이드를 유효성분으로 포함하는, 치주 질환의 예방 또는 개선을 위한 구강용 외용제 조성물을 제공한다.In addition, the present invention provides a composition for oral external application for preventing or improving periodontal disease, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
또한, 본 발명은 서열번호 1의 아미노산 서열로 이루어진 펩타이드를 유효성분으로 포함하는, 치주 질환의 예방 또는 개선용 건강기능식품을 제공한다.In addition, the present invention provides a health functional food for preventing or improving periodontal disease, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
상기 치주 질환의 예방 또는 치료용 약학적 조성물, 경구용 조성물, 구강용 외용제 조성물 및 건강기능식품에서 언급된 모든 사항은 모순되지 않는 한 동일하게 적용된다.All matters mentioned in the above pharmaceutical compositions, oral compositions, external oral compositions, and health functional foods for the prevention or treatment of periodontal disease apply equally unless contradictory.
본 발명의 치주 질환의 예방 또는 치료용 약학적 조성물, 경구용 조성물, 구강용 외용제 조성물 및 건강기능식품은 SDF1δ 유래 펩타이드 S10을 이용하여 치주염을 유발하는 포르피로모나스 진지발리스(Porphyromonas gingivalis)를 비롯한 다양한 균을 억제함으로써 염증을 완화하고 치조골 형성을 활성화시키는 효과를 갖는다.The pharmaceutical composition, oral composition, oral external preparation composition, and health functional food for the prevention or treatment of periodontal disease of the present invention include Porphyromonas gingivalis , which causes periodontitis, using SDF1δ-derived peptide S10. It has the effect of alleviating inflammation and activating alveolar bone formation by suppressing various bacteria.
본 발명의 효과들은 이상에서 언급한 효과들로 제한되지 않으며, 언급되지 않은 또 다른 효과들은 청구범위의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description of the claims.
도 1은 본 발명의 일 실시예에 따른 S10의 서열이 유래된 기질 세포 유래 인자 1 동형 델타(stromal cell-derived factor 1 isoform delta) 전구체 [호모 사피엔스]의 서열을 나타낸 것이다.
도 2는 본 발명의 일 실험예에 따라 치주 질환의 원인균인 포르피로모나스 진지발리스(Porphyromonas gingivalis, Pg)로 감염된 THP-1 유래 대식세포에서의 S10의 항염증 효과를 확인한 그래프 및 이미지로, (a)는 사이토카인 생성, (b)는 TLR 신호분자, (c) 및 (d)는 MAPKs와 NF-κB의 발현 변화를 나타낸 것이다.
도 3은 본 발명의 일 실험예에 따라 치주 질환의 원인균인 포르피로모나스 진지발리스(Pg)로 감염된 THP-1 유래 대식세포에서의 S10의 염증복합체(inflammasome) 활성화 억제 효과를 확인한 것으로, (a) 내지 (c)는 염증복합체 관련 인자들의 발현 변화를 나타낸 것이고, (d) 및 (e)는 자가포식 활성화 효과를 실시간 PCR과 웨스턴 블롯(western blot)으로 각각 확인한 것이다.
도 4는 본 발명의 일 실험예에 따라 치주 질환의 원인균인 포르피로모나스 진지발리스(Pg)로 감염된 THP-1 유래 대식세포에서의 S10의 소포체 스트레스(ER stress) 억제와 활성 산소종 억제 효과를 확인한 것으로, (a)는 실시간 PCR, (b)는 웨스턴 블롯 결과이며, (c) 미토콘드리아 활성 산소종 및 (d) ER 매개 활성 산소종의 변화를 나타낸 것이다.
도 5는 본 발명에 따른 일 실험예에 따라 치주 질환의 원인균인 포르피로모나스 진지발리스로 감염된 골 생성 세포로 알려진 MC3T3-E1 세포의 골 파괴 억제 효과를 확인한 그래프 및 이미지이다.
도 6은 본 발명에 따른 일 실험예에 따라 포르피로모나스 진지발리스에 의해 유발된 치조골 소실에 대한 S10의 영향을 확인한 것으로, (a)는 노출된 골 표면적을 나타낸 막대 그래프이고, (b)는 치조골 소실 정도를 micro-CT로 측정한 것으로, 세 어금니의 백악-법랑질 접합부와 치조골 능선 사이의 면적은 ImageJ를 사용하여 계산되었다.
도 7은 본 발명의 일 실험예에 따라 치주 질환의 원인이 되는 다양한 균의 항염증 효과를 확인한 그래프로, Pg는 포르피로모나스 진지발리스(Porphyromonas gingivalis), Aa는 아그레가티박터 액티노마이세템코미탄스(Aggregatibacter actinomycetemcomitans), Fn은 퓨조박테리움 뉴클레아툼(Fusobacterium nucleatum), Sm은 스트렙토코쿠스 뮤탄스(Streptococcus mutans), 및 Td는 트레포네마 덴티콜라(Treponema denticola)에 감염된 대식세포를 의미한다.Figure 1 shows the sequence of the stromal cell-derived factor 1 isoform delta precursor [Homo sapiens] from which the sequence of S10 is derived according to an embodiment of the present invention.
Figure 2 is a graph and image confirming the anti-inflammatory effect of S10 in THP-1 derived macrophages infected with Porphyromonas gingivalis (Pg), the causative agent of periodontal disease, according to an experimental example of the present invention. (a) shows cytokine production, (b) shows TLR signaling molecules, and (c) and (d) show changes in expression of MAPKs and NF-κB.
Figure 3 shows the inhibitory effect of S10 on inflammatory complex (inflammasome) activation in THP-1 derived macrophages infected with Porphyromonas gingivalis (Pg), the causative agent of periodontal disease, according to an experimental example of the present invention, ( A) to (c) show changes in expression of inflammatory complex-related factors, and (d) and (e) show the autophagy activation effect confirmed by real-time PCR and Western blot, respectively.
Figure 4 shows the effects of S10 on ER stress inhibition and reactive oxygen species inhibition in THP-1 derived macrophages infected with Porphyromonas gingivalis (Pg), the causative agent of periodontal disease, according to an experimental example of the present invention. This was confirmed, (a) is the result of real-time PCR, (b) is the Western blot result, and (c) shows changes in mitochondrial reactive oxygen species and (d) ER-mediated reactive oxygen species.
Figure 5 is a graph and image confirming the bone destruction inhibition effect of MC3T3-E1 cells, known as osteogenic cells, infected with Porphyromonas gingivalis, the causative agent of periodontal disease, according to an experimental example according to the present invention.
Figure 6 confirms the effect of S10 on alveolar bone loss caused by Porphyromonas gingivalis according to an experimental example according to the present invention, (a) is a bar graph showing the exposed bone surface area, and (b) is a bar graph showing the exposed bone surface area. The degree of alveolar bone loss was measured using micro-CT, and the area between the cementum-enamel junction of the three molars and the alveolar bone ridge was calculated using ImageJ.
Figure 7 is a graph confirming the anti-inflammatory effect of various bacteria causing periodontal disease according to an experimental example of the present invention, where Pg is Porphyromonas gingivalis and Aa is Aggregatibacter actinomycetes. Macrophages infected with Aggregatibacter actinomycetemcomitans , Fn is Fusobacterium nucleatum , Sm is Streptococcus mutans , and Td is Treponema denticola . means.
본 명세서에서 사용되는 용어는 본 발명에서의 기능을 고려하면서 가능한 현재 널리 사용되는 일반적인 용어들을 선택하였으나, 이는 당 분야에 종사하는 기술자의 의도 또는 판례, 새로운 기술의 출현 등에 따라 달라질 수 있다. 또한, 특정한 경우는 출원인이 임의로 선정한 용어도 있으며, 이 경우 해당되는 발명의 설명 부분에서 상세히 그 의미를 기재할 것이다. 따라서 본 발명에서 사용되는 용어는 단순한 용어의 명칭이 아닌, 그 용어가 가지는 의미와 본 발명의 전반에 걸친 내용을 토대로 정의되어야 한다.The terms used in this specification are general terms that are currently widely used as much as possible while considering the function in the present invention, but this may vary depending on the intention or precedent of a person skilled in the art, the emergence of new technology, etc. In addition, in certain cases, there are terms arbitrarily selected by the applicant, and in this case, the meaning will be described in detail in the description of the relevant invention. Therefore, the terms used in the present invention should be defined based on the meaning of the term and the overall content of the present invention, rather than simply the name of the term.
다르게 정의되지 않는 한, 기술적이거나 과학적인 용어를 포함해서 여기서 사용되는 모든 용어들은 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에 의해 일반적으로 이해되는 것과 동일한 의미를 가지고 있다. 일반적으로 사용되는 사전에 정의되어 있는 것과 같은 용어들은 관련 기술의 문맥상 가지는 의미와 일치하는 의미를 가지는 것으로 해석되어야 하며, 본 출원에서 명백하게 정의하지 않는 한, 이상적이거나 과도하게 형식적인 의미로 해석되지 않는다.Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the technical field to which the present invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related technology, and unless clearly defined in the present application, should not be interpreted in an ideal or excessively formal sense. No.
수치 범위는 상기 범위에 정의된 수치를 포함한다. 본 명세서에 걸쳐 주어진 모든 최대의 수치 제한은 낮은 수치 제한이 명확히 쓰여져 있는 것처럼 모든 더 낮은 수치 제한을 포함한다. 본 명세서에 걸쳐 주어진 모든 최소의 수치 제한은 더 높은 수치 제한이 명확히 쓰여져 있는 것처럼 모든 더 높은 수치 제한을 포함한다. 본 명세서에 걸쳐 주어진 모든 수치 제한은 더 좁은 수치 제한이 명확히 쓰여져 있는 것처럼, 더 넓은 수치 범위 내의 더 좋은 모든 수치 범위를 포함할 것이다.The numerical range includes the values defined in the range above. Every maximum numerical limit given throughout this specification includes all lower numerical limits as if the lower numerical limit were explicitly written out. Every minimum numerical limit given throughout this specification includes every higher numerical limit as if such higher numerical limit was clearly written. All numerical limits given throughout this specification will include all better numerical ranges within the broader numerical range, as if the narrower numerical limits were clearly written.
이하, 본 발명의 실시예를 상세히 기술하나, 하기 실시예에 의해 본 발명이 한정되지 아니함은 자명하다.Hereinafter, examples of the present invention will be described in detail, but it is obvious that the present invention is not limited to the following examples.
치주 질환의 예방 또는 치료용 약학적 조성물Pharmaceutical composition for preventing or treating periodontal disease
본 발명은 SDF1δ 유래 펩타이드 S10을 유효성분으로 포함하는, 치주 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating periodontal disease, comprising SDF1δ-derived peptide S10 as an active ingredient.
상기 SDF1δ 유래 펩타이드 S10은 하기 서열번호 1의 아미노산 서열로 이루어질 수 있다.The SDF1δ-derived peptide S10 may consist of the amino acid sequence of SEQ ID NO: 1 below.
서열번호 1 : ISAAPAGKRV IAGARSEQ ID NO: 1: ISAAPAGKRV IAGAR
상기 치주 질환은 잇몸뼈 및 인접 조직의 질환을 말한다. 치주 질환은 세균 감염으로부터 시작되어 세균의 독소에 의해 염증반응이 진행되면 잇몸과 치아 사이에 치주낭(periodontal pocket)이 형성되고, 질환이 심해질수록 치주낭의 깊이가 깊어져서 치주인대로 염증이 파급되며 골소실이 일어나게 된다. 또는 치조골에서 골형성과 골흡수의 균형이 깨어져 골흡수가 골형성을 초과하여 골량이 한계 이하로 감소하면 치주 질환의 일종인 치조골형성장애가 발생한다.The periodontal disease refers to a disease of gum bones and adjacent tissues. Periodontal disease begins with bacterial infection, and as the inflammatory reaction progresses due to bacterial toxins, periodontal pockets are formed between the gums and teeth. As the disease worsens, the depth of the periodontal pockets deepens, and inflammation spreads to the periodontal ligament and bone. Disappearance occurs. Alternatively, when the balance between bone formation and bone resorption in the alveolar bone is broken, bone resorption exceeds bone formation, and bone mass decreases below the limit, alveolar bone dysplasia, a type of periodontal disease, occurs.
보다 구체적으로, 상기 치주 질환은 치은염(gingivitis), 치주염(periodontal inflammation), 치조골 파손(alveolar bone breakage) 및 치조골형성장애(alveolar bone osteodystrophy)로 이루어진 군으로부터 선택된 1종 이상일 수 있다.More specifically, the periodontal disease may be one or more types selected from the group consisting of gingivitis, periodontitis, alveolar bone breakage, and alveolar bone osteodystrophy.
상기 치주 질환은 포르피로모나스 진지발리스(Porphyromonas gingivalis), 아그레가티박터 액티노마이세템코미탄스(Aggregatibacter actinomycetemcomitans), 퓨조박테리움 뉴클레아툼(Fusobacterium nucleatum), 스트렙토코쿠스 뮤탄스(Streptococcus mutans), 및 트레포네마 덴티콜라(Treponema denticola)로 이루어진 군에서 선택된 하나 이상의 균으로부터 발생된 질환일 수 있으나, 이에 제한되는 것은 아니다.The periodontal disease is caused by Porphyromonas gingivalis , Aggregatibacter actinomycetemcomitans , Fusobacterium nucleatum , and Streptococcus mutans. ), and Treponema denticola . It may be a disease caused by one or more bacteria selected from the group consisting of, but is not limited to this.
상기 균은 구강 내 치수 감염에서 주로 발견되는 세균 종으로, 이 균주들이 과다 증식한 구강에서 충치, 치주염 및 구취 등의 다양한 치주 질환 증상이 나타날 수 있다.The above bacteria are a bacterial species mainly found in oral pulp infections, and various periodontal disease symptoms such as cavities, periodontitis, and bad breath may appear in the oral cavity where these strains overproliferate.
또한, 상기 치조골형성장애는 치조골다공증(alveolar bone osteoporosis), 치조골연화증(alveolar bone osteomalacia) 및 치조골감소증(alveolar bone osteopenia)으로 이루어진 군으로부터 선택된 1종 이상일 수 있다.In addition, the alveolar bone dysplasia may be one or more types selected from the group consisting of alveolar bone osteoporosis, alveolar bone osteomalacia, and alveolar bone osteopenia.
상기 SDF1δ 유래 펩타이드 S10은 포르피로모나스 진지발리스(Porphyromonas gingivalis), 아그레가티박터 액티노마이세템코미탄스(Aggregatibacter actinomycetemcomitans), 퓨조박테리움 뉴클레아툼(Fusobacterium nucleatum), 스트렙토코쿠스 뮤탄스(Streptococcus mutans), 및 트레포네마 덴티콜라(Treponema denticola)로 이루어진 군에서 선택된 하나 이상의 발현을 억제할 수 있다. The SDF1δ-derived peptide S10 is Porphyromonas gingivalis , Aggregatibacter actinomycetemcomitans , Fusobacterium nucleatum , and Streptococcus mutans ( Streptococcus mutans ), and Treponema denticola ( Treponema denticola ) can suppress the expression of one or more selected from the group consisting of.
보다 구체적으로, 상기 SDF1δ 유래 펩타이드 S10은 치주염 원인균인 포르피로모나스 진지발리스에 의한 치주 질환, 예컨대 THP-1 유래 대식세포에서의 항염 효과, 사이토카인 생성, TLR 신호 분자, MAPKs와 NF-κB의 발현 억제 효과 등을 가질 수 있다. 또한, 상기 SDF1δ 유래 펩타이드 S10은 치주염 원인균인 포르피로모나스 진지발리스로 감염된 MC3T3-E1 세포(골 생성 세포)에서 골 파괴 억제 효과, 골 형성 인자인 RUNX2, BMP-2/4, OSX 등의 발현 증가 효과를 가질 수 있다.More specifically, the SDF1δ-derived peptide S10 has anti-inflammatory effects on periodontal diseases caused by Porphyromonas gingivalis, the causative bacteria of periodontitis, such as THP-1-derived macrophages, cytokine production, TLR signaling molecules, MAPKs and NF-κB. It may have an expression inhibition effect, etc. In addition, the SDF1δ-derived peptide S10 has an inhibitory effect on bone destruction and increases the expression of osteogenic factors such as RUNX2, BMP-2/4, and OSX in MC3T3-E1 cells (osteogenic cells) infected with Porphyromonas gingivalis, the causative agent of periodontitis. It can have an effect.
상기 약학적 조성물은 상기 SDF1δ 유래 펩타이드 S10을 유효성분으로 함유하고, 약제학적으로 허용가능한 담체를 포함할 수 있으며, 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 및 멸균 주사용액의 형태로 제제화될 수 있다. 상기 약학적으로 허용 가능한 담체는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함할 수 있다.The pharmaceutical composition contains the SDF1δ-derived peptide S10 as an active ingredient, may include a pharmaceutically acceptable carrier, and can be formulated into powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols according to conventional methods. It can be formulated in the form of oral dosage forms, topical preparations, and sterile injectable solutions. The pharmaceutically acceptable carriers include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline. It may include cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
또한, 본 발명의 약학적 조성물은 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 포함할 수 있다. 경구용 고형 제제는 정제, 환제, 산제, 과립제, 캡슐제 등을 포함하며, 이러한 고형제제는 적어도 하나이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 포함할 수 있으며, 마그네슘 스테아레이트, 탈크 같은 윤활제 등을 포함할 수 있다. 경구용 액상 제제는 현탁제, 내용액제, 유제, 시럽제 등을 포함하며, 물, 리퀴드 파라핀 등의 희석제, 습윤제, 감미제, 방향제, 보존제 등을 포함할 수 있다. 비경구용 제제는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결 건조 제제를 포함하며, 비수성 용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르류 등을 포함할 수 있다.Additionally, the pharmaceutical composition of the present invention may contain diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Oral solid preparations include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient, such as starch, calcium carbonate, sucrose, or lactose. ), gelatin, etc., and may include lubricants such as magnesium stearate and talc. Oral liquid preparations include suspensions, oral solutions, emulsions, syrups, etc., and may contain diluents such as water and liquid paraffin, humectants, sweeteners, fragrances, and preservatives. Parenteral preparations include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, and freeze-dried preparations. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and ethyl oleate. It may include injectable esters such as .
본 발명의 약학적 조성물은 정맥내, 동맥내, 복강내, 근육내, 동맥내, 복강내, 흉골내, 경피, 비측내, 흡입, 국소, 직장, 경구, 안구내 또는 피내 경로를 통해 통상적인 방식으로 투여할 수 있다. 바람직하게는 본 발명의 약학적 조성물은 경구 또는 피하로 투여할 수 있으나, 투여 경로는 이에 한정되는 것은 아니다.The pharmaceutical composition of the present invention can be administered via conventional routes: intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, intranasal, inhalational, topical, rectal, oral, intraocular or intradermal. It can be administered in any way. Preferably, the pharmaceutical composition of the present invention can be administered orally or subcutaneously, but the route of administration is not limited thereto.
본 발명의 약학적 조성물에 있어서, 유효성분의 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 경우에 따라 적절하게 선택될 수 있다. 예를 들면, 상기 SDF1δ 유래 펩타이드 S10은 1일 0.0001 내지 500 mg/kg으로, 바람직하게는 0.01 내지 300 mg/kg의 용량으로 투여할 수 있으며, 상기 투여는 하루에 한번 또는 수회 나누어 투여할 수도 있다.In the pharmaceutical composition of the present invention, the dosage of the active ingredient varies depending on the patient's condition and weight, degree of disease, drug type, administration route and period, but may be appropriately selected depending on the case. For example, the SDF1δ-derived peptide S10 can be administered at a dose of 0.0001 to 500 mg/kg per day, preferably 0.01 to 300 mg/kg, and may be administered once a day or in divided doses. .
치주 질환의 예방 또는 개선을 위한 경구용 조성물Oral composition for preventing or improving periodontal disease
본 발명은 서열번호 1의 아미노산 서열로 이루어진 SDF1δ 유래 펩타이드 S10을 유효성분으로 포함하는, 치주 질환의 예방 또는 개선을 위한 경구용 조성물을 제공한다.The present invention provides an oral composition for preventing or improving periodontal disease, comprising peptide S10 derived from SDF1δ consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
이에 상응하는 특징들은 상술된 부분에서 대신할 수 있다.Corresponding features may be substituted for the parts described above.
본 발명에 사용된 용어 "경구용 조성물"은 파골세포의 분화 억제, 백악질 및 잇몸 조직 회복치 조정 거리를 감소 효과 등을 가지는 경구로 투입되는 조성물이다. The term “oral composition” used in the present invention refers to a composition administered orally that has the effect of inhibiting the differentiation of osteoclasts and reducing the adjustment distance for cementum and gum tissue recovery values.
상기 경구용 조성물에 있어서, 그 제형은 예컨대 필름, 치약, 구강양치용액, 연고제, 분무제, 드레싱용액, 도포제, 치실 또는 치주 포대로 제형화될 수 있다.In the oral composition, the formulation may be, for example, a film, toothpaste, mouthwash, ointment, spray, dressing solution, liniment, dental floss, or periodontal bag.
상기 경구용 조성물은 상기 SDF1δ 유래 펩타이드 S10을 유효 성분으로 함유하고, 이외에 습윤제, 기포제, 보존제, 감미제, 점증제, 수용성 폴리머, 향료 및 기타 성분 등을 함유할 수 있다. 본 발명에 따른 첨가제는 상기 SDF1δ 유래 펩타이드 S10 100 중량부에 대해 0.1 ~ 90 중량부 포함되는 것이 바람직하나 이에 한정되는 것은 아니다.The oral composition contains the SDF1δ-derived peptide S10 as an active ingredient, and may also contain wetting agents, foaming agents, preservatives, sweeteners, thickeners, water-soluble polymers, fragrances, and other ingredients. The additive according to the present invention is preferably contained in an amount of 0.1 to 90 parts by weight based on 100 parts by weight of the SDF1δ-derived peptide S10, but is not limited thereto.
상기 습윤제는 경구용 조성물 내의 물의 증발을 억제하기 위한 성분으로서, 글리세린, 소르비톨액, 비결성소르비톨액, 폴리에틸렌글리콜, 프로필렌글리콜 등 다가 알코올으로 이루어진 군에서 선택된 1종 이상을 혼합하여 사용할 수 있다.The humectant is an ingredient for suppressing evaporation of water in the oral composition, and can be used by mixing one or more types selected from the group consisting of polyhydric alcohols such as glycerin, sorbitol solution, non-consolidated sorbitol solution, polyethylene glycol, and propylene glycol.
상기 기포제는 조성물 내의 수용성 성분과 유용성 성분과의 유화 또는 가용화 효과를 지니며 구강 내에서 세정 효과를 갖도록 하는 성분으로서, 라우릴황산나트륨, N-라우로일살코실산나트륨, N-장쇄아실글루탐산염, 자당지방산에스테르, 폴리옥시에틸렌경화피마자유, 소르비탄 지방산에스테르, 폴리옥시에틸렌폴리옥시프로필렌코폴리머 등의 음이온 및 비이온 계면활성제로 이루어진 군에서 선택된 1종 이상을 혼합하여 사용할 수 있다.The foaming agent is an ingredient that has an emulsifying or solubilizing effect between the water-soluble and oil-soluble components in the composition and has a cleaning effect in the oral cavity, including sodium lauryl sulfate, sodium N-lauroyl sarcosylate, N-long-chain acyl glutamate, One or more types selected from the group consisting of anionic and nonionic surfactants such as sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene copolymer can be used in combination.
상기 보존제는 보존기간을 연장하기 위한 성분으로, 파라옥시안식향산메틸, 안식향산, 안식향산 나트륨 등을 사용할 수 있다.The preservative is an ingredient to extend the storage period and may include methyl paraoxybenzoate, benzoic acid, sodium benzoate, etc.
상기 감미제 및/또는 향료는 제품 사용시 맛을 좋게 하고 뒷맛을 상쾌하게 하기 위한 성분으로서, 감미제로는 사카린나트륨, 아스파탐, 스테비오사이드, 감초산 등을 사용할 수 있고, 향료로는 페퍼민트, 스페아민트오일, 멘톨, 카르본, 아네톨, 오이게놀 등을 혼합하여 사용할 수 있다.The sweetener and/or flavoring agent is an ingredient to improve the taste and refresh the aftertaste when using the product. Sweeteners include sodium saccharin, aspartame, stevioside, and licorice acid, and flavoring agents include peppermint, spearmint oil, Menthol, carvone, anethole, eugenol, etc. can be mixed and used.
상기 점증제는 조성물 내의 물에 불용성인 무기분말성분과 액상성분을 결합시켜 시간에 따른 상분리를 방지하며, 조성물에 점성을 부여하는 성분으로서, 카르복시메틸셀룰로오스(CMC), 카라기난, 알킨산나트륨, 아라비아 고무, 잔탄검, 기타 검류 등으로 이루어진 군에서 선택된 1종 이상을 혼합하여 사용할 수 있다.The thickener is an ingredient that prevents phase separation over time by combining the water-insoluble inorganic powder component and the liquid component in the composition and adds viscosity to the composition, including carboxymethyl cellulose (CMC), carrageenan, sodium alkylate, and arabic. One or more types selected from the group consisting of rubber, xanthan gum, and other gums can be mixed and used.
상기 수용성 폴리머는 하이드록시프로필 셀룰로오스(Hydroxypropyl cellulose-Klucel TM), 하이드록시프로필 메틸셀룰로오스(Hydroxypropyl methylcellulose), 하이드록시 에틸셀룰로오스(Hydroxy ethylcellulose), 에틸셀룰로오스(ethylcellulose), 카르복시메틸 셀룰로오스(Carboxymethylcellulose), 덱스트란(Dextran), 가우어검(gaur-gum), PVP(polyvinyl pyrrolidone), 펙틴(pectins), 녹말(stacrches), 젤라틴(gelatin), 카세인(casein), 알긴산 나트륨(sodium alginate), 폴리에틸렌 글리콜(polyethlyene glycol), 및 폴리비닐 글리콜(polyvinyl glycol) 등으로 이루어진 군에서 선택된 1종 이상을 혼합하여 사용할 수 있다.The water-soluble polymer is hydroxypropyl cellulose-Klucel TM, hydroxypropyl methylcellulose, hydroxy ethylcellulose, ethylcellulose, carboxymethylcellulose, and dextran. (Dextran), gaur-gum, PVP (polyvinyl pyrrolidone), pectins, starches, gelatin, casein, sodium alginate, polyethlyene glycol ), and polyvinyl glycol, etc. can be used in combination with one or more selected from the group consisting of.
상기 기타 첨가제로서 pH 조절을 위한 구연산나트륨 등의 안정제, 충치 억제 기능을 지니는 불소제, 염화아연 등의 수렴제, 청색1호와 같은 식용색소를 사용할 수 있다.As the other additives, stabilizers such as sodium citrate for pH adjustment, fluorine agents with a cavity-inhibiting function, astringents such as zinc chloride, and food coloring such as Blue No. 1 can be used.
치주 질환의 예방 또는 개선을 위한 구강용 외용제 조성물Oral topical composition for preventing or improving periodontal disease
본 발명은 서열번호 1의 아미노산 서열로 이루어진 SDF1δ 유래 펩타이드 S10을 유효성분으로 포함하는, 치주 질환의 예방 또는 개선을 위한 구강용 외용제 조성물을 제공한다.The present invention provides an oral topical composition for preventing or improving periodontal disease, comprising SDF1δ-derived peptide S10 having the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
이에 상응하는 특징들은 상술된 부분에서 대신할 수 있다.Corresponding features may be substituted for the parts described above.
상기 구강용 외용제는 특별히 이에 제한되지 않으나, 바람직하게는 연고제, 로션제, 스프레이제, 패취제, 크림제, 산제, 현탁제, 겔제 또는 젤의 형태로 제조되어 사용될 수 있다. 바람직하게는 필름, 치약, 구강양치용액, 연고제, 분무제, 드레싱용액, 도포제, 치실 또는 치주 포대로 제형화될 수 있다. 본 발명의 구강용 외용제를 사용하는 경우, 추가로 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제 등과 같이 구강용 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 통상적으로 사용되는 보조제를 함유할 수 있다.The oral external preparation is not particularly limited thereto, but is preferably prepared and used in the form of ointment, lotion, spray, patch, cream, powder, suspension, gel or gel. Preferably, it can be formulated as a film, toothpaste, oral rinse solution, ointment, spray, dressing solution, liniment, dental floss, or periodontal bag. When using the oral external preparation of the present invention, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or non-ionic are added. Any other ingredients commonly used in oral external preparations, such as emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, etc. May contain commonly used auxiliaries.
치주 질환의 예방 또는 개선용 건강기능식품Health functional food for preventing or improving periodontal disease
본 발명은 서열번호 1의 아미노산 서열로 이루어진 SDF1δ 유래 펩타이드 S10을 유효성분으로 포함하는, 치주 질환의 예방 또는 개선용 건강기능식품을 제공한다.The present invention provides a health functional food for preventing or improving periodontal disease, comprising SDF1δ-derived peptide S10 consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
이에 상응하는 특징들은 상술된 부분에서 대신할 수 있다.Corresponding features may be substituted for the parts described above.
본 발명에 사용된 용어 "건강기능식품"이라 함은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The term "health functional food" used in the present invention refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with Act No. 6727 on Health Functional Food, and "functional" refers to food. This means taking it for the purpose of controlling nutrients for the structure and function of the human body or obtaining useful effects for health purposes such as physiological effects.
상기 건강기능식품은 통상의 방법에 따라 제조하며, 담체와 함께 건조한 후 캡슐화하거나 기타 정제, 과립, 분말, 음료, 죽 등의 형태로 제형화할 수 있으며, 상기 기재한 것 외에도 모든 식품 형태로 제조 가능하다.The health functional food is manufactured according to a conventional method, and can be dried with a carrier and then encapsulated or formulated into other forms such as tablets, granules, powder, beverages, porridge, etc. In addition to those listed above, it can be manufactured in all food forms. do.
본 발명의 건강기능식품은 통상의 식품 첨가물을 포함할 수 있으며, "식품 첨가물"로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안정청에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The health functional food of the present invention may contain common food additives, and its suitability as a “food additive” is determined in accordance with the general provisions of the Food Additive Code and General Test Methods approved by the Food and Drug Safety Administration, unless otherwise specified. It is determined in accordance with the relevant standards and standards.
상기 "식품 첨가물 공전"에 기재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류들을 들 수 있다.Items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as reduced color, licorice extract, crystalline cellulose, high-lyan pigment, and guar gum, L -Combined preparations include sodium glutamate preparations, noodle additive alkaline preparations, preservative preparations, and tar coloring preparations.
본 발명의 건강기능성식품은 식품 및 음료 등에 다양하게 이용될 수 있으며, 예컨대, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능성 보조 식품, 식품 첨가제 등에 사용될 수 있고, 분말, 과립, 정제, 캡슐, 환 또는 음료인 형태로 사용할 수 있다. 상기 기재한 것 외에도 모든 식품 형태일 수 있다.The health functional food of the present invention can be used in a variety of foods and beverages, for example, various foods, beverages, gum, tea, vitamin complexes, health functional supplements, food additives, etc., and can be used in powders, granules, tablets, etc. It can be used in capsule, pill or beverage form. In addition to those described above, it may be in any food form.
본 발명의 이점 및 특징, 그리고 그것들을 달성하는 방법은 상세하게 후술되어 있는 실시예들을 참조하면 명확해 질 것이다. 그러나, 본 발명은 이하에서 개시되는 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 수 있으며, 단지 실시예들은 본 발명의 개시가 완전하도록 하고, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 발명의 범주를 완전하세 알려 주기 위해 제공되는 것이며, 본 발명은 청구항의 범주에 의해 정의될 뿐이다.The advantages and features of the present invention and methods for achieving them will become clear with reference to the embodiments described in detail below. However, the present invention is not limited to the embodiments disclosed below and may be implemented in various different forms, and only the embodiments are provided to ensure that the disclosure of the present invention is complete, and are provided by those skilled in the art It is provided to fully inform those who have the scope of the invention, and the present invention is only defined by the scope of the claims.
<실시예 1> SDF1δ 유래 펩타이드 S10<Example 1> SDF1δ-derived peptide S10
S10의 서열은 기질 세포 유래 인자 1 동형 델타(stromal cell-derived factor 1 isoform delta) 전구체 [호모 사피엔스] (Accession:NP_001171605.1) (도 1) 에서 가져왔다. SDF1 유래 펩타이드 샘플로 테스트 후, 선택된 서열의 재조합 단백질을 펩트로텍(Peptrotech)에서 합성하였다(S10).The sequence of S10 was taken from the stromal cell-derived factor 1 isoform delta precursor [Homo sapiens] (Accession: NP_001171605.1) (Figure 1). After testing with SDF1-derived peptide samples, recombinant proteins of the selected sequences were synthesized at Peptrotech (S10).
SDF1P-10 (s10): ISAAPAGKRV IAGARSDF1P-10 (s10): ISAAPAGKRV IAGAR
<실험예 1> 포르피로모나스 진지발리스(<Experimental Example 1> Porphyromonas gingivalis ( Porphyromonas gingivalisPorphyromonas gingivalis )로 감염된 THP-1 유래 대식세포에서의 항염증 효과 확인) confirmed anti-inflammatory effect in THP-1 derived macrophages infected with
상기 실시예 1에 따라 합성된 SDF1δ 유래 펩타이드 S10이 치주 질환의 원인균인 포르피로모나스 진지발리스로 감염된 THP-1 유래 대식세포에서 항염증 효과를 가지는지 여부를 확인하였다.It was confirmed whether the SDF1δ-derived peptide S10 synthesized according to Example 1 had an anti-inflammatory effect in THP-1-derived macrophages infected with Porphyromonas gingivalis, the causative agent of periodontal disease.
먼저, 포르피로모나스 진지발리스(Porphyromonas gingivalis) (strain 33277)는 37℃에서 5 mg/mL 헤민(hemin) 및 0.5 mg/mL 3-피틸-메나디온(3-phytyl-menadione)(비타민 K)을 포함하는 Gifu 혐기성 배지 브로스에서 혐기성 배양 (80% 질소, 10% 수소 및 10% CO2 포함)하였다. 박테리아를 세척하고 RPMI 배지에 재현탁하여 50의 감염 다중도(multiplicity of infection, MOI)에서 THP-1 세포를 감염시켰다. 이 후, 상기 SDF1δ 유래 펩타이드 S10을 상기 포르피로모나스 진지발리스(Pg)에 감염된 THP-1 유래 대식세포에 점적하였다.First, Porphyromonas gingivalis (strain 33277) contains 5 mg/mL hemin and 0.5 mg/mL 3-phytyl-menadione (vitamin K) at 37°C. Anaerobic culture was performed in Gifu anaerobic medium broth containing (80% nitrogen, 10% hydrogen and 10% CO 2 ). Bacteria were washed and resuspended in RPMI medium to infect THP-1 cells at a multiplicity of infection (MOI) of 50. Afterwards, the SDF1δ-derived peptide S10 was instilled into THP-1-derived macrophages infected with Porphyromonas gingivalis (Pg).
그 결과, 도 2를 참조하면, 상기 실시예 1에서 제작된 SDF1δ 유래 펩타이드 S10이 포르피로모나스 진지발리스(Pg)로 감염된 THP-1 유래 대식세포에서 사이토카인 생성을 감소시키고 (a), TLR 신호 분자(b), MAPKs와 NF-κB의 발현(c, d)을 억제하는 것으로 나타났다.As a result, referring to Figure 2, SDF1δ-derived peptide S10 produced in Example 1 reduced cytokine production in THP-1-derived macrophages infected with Porphyromonas gingivalis (Pg) (a), TLR It was shown to inhibit the expression of signaling molecules (b), MAPKs and NF-κB (c, d).
더불어, 도 3을 참조하면, 상기 실시예 1에서 제작된 SDF1δ 유래 펩타이드 S10에 의해 상기 포르피로모나스 진지발리스(Pg)로 감염된 THP-1 유래 대식세포의 염증복합체(inflammasome)의 활성화가 억제되는 것으로 나타났다.In addition, referring to Figure 3, the activation of the inflammatory complex (inflammasome) of THP-1 derived macrophages infected with Porphyromonas gingivalis (Pg) is inhibited by the SDF1δ-derived peptide S10 produced in Example 1. It was found that
즉, 이를 통해 상기 SDF1δ 유래 펩타이드 S10이 항염증 효과를 가짐을 확인할 수 있다.In other words, it can be confirmed that the SDF1δ-derived peptide S10 has an anti-inflammatory effect.
<실험예 2> 포르피로모나스 진지발리스(<Experimental Example 2> Porphyromonas gingivalis ( Porphyromonas gingivalisPorphyromonas gingivalis )로 감염된 THP-1 유래 대식세포에서의 소포체 스트레스(ER stress) 억제와 활성 산소종 억제 효과 확인) Confirmed the effect of suppressing ER stress and suppressing reactive oxygen species in THP-1-derived macrophages infected with
RNA seq을 통해 치주염 환자에서 치주염 정도에 따라 소포체 스트레스(ER stres)의 인자들이 증가하는 것을 확인한 후, 상기 실시예 1에 따라 합성된 SDF1δ 유래 펩타이드 S10이 치주 질환의 원인균인 포르피로모나스 진지발리스로 감염된 THP-1 유래 대식세포에서의 ER stress 억제와 활성 산소종 억제 효과를 Real time PCR과 western blot을 통해 확인하였다. After confirming through RNA seq that the factors of endoplasmic reticulum stress (ER stres) increase according to the degree of periodontitis in periodontitis patients, the SDF1δ-derived peptide S10 synthesized according to Example 1 was identified as Porphyromonas gingivalis, the causative agent of periodontal disease. The effects of suppressing ER stress and reactive oxygen species in infected THP-1-derived macrophages were confirmed through real-time PCR and western blot.
그 결과, 도 4에 나타난 바와 같이, 포르피로모나스 진지발리스로 감염된 THP-1 유래 대식세포에서 증가했던 ER stress 발현과 mitochondrial ROS가 상기 실시예 1에서 제작된 SDF1δ 유래 펩타이드 S10에 의해 억제되는 것을 확인할 수 있다.As a result, as shown in Figure 4, it was confirmed that ER stress expression and mitochondrial ROS, which increased in THP-1-derived macrophages infected with Porphyromonas gingivalis, were suppressed by SDF1δ-derived peptide S10 prepared in Example 1. You can.
<실험예 3> 포르피로모나스 진지발리스(<Experimental Example 3> Porphyromonas gingivalis ( Porphyromonas gingivalisPorphyromonas gingivalis )로 감염된 MC3T3-E1 세포(골생성세포)에서의 골 파괴 억제 효과 확인) confirmed the inhibitory effect on bone destruction in MC3T3-E1 cells (osteogenic cells) infected with
상기 실시예 1에 따라 합성된 SDF1δ 유래 펩타이드 S10이 치주 질환의 원인균인 포르피로모나스 진지발리스로 감염된 골 생성 세포로 알려진 MC3T3-E1 세포의 골 파괴 억제 효과를 확인하기 위해, 상기 S10을 포르피로모나스 진지발리스로 감염된 MC3T3-E1 세포(골생성세포)에 점적하였다.In order to confirm the effect of the SDF1δ-derived peptide S10 synthesized according to Example 1 on suppressing bone destruction in MC3T3-E1 cells, known as osteogenic cells infected with Porphyromonas gingivalis, the causative agent of periodontal disease, S10 was mixed with Porphyromonas gingivalis. It was spotted on MC3T3-E1 cells (osteogenic cells) infected with gingivalis.
그 결과, 도 5를 참조하면, 상기 실시예 1에서 제작된 SDF1δ 유래 펩타이드 S10에 의해 포르피로모나스 진지발리스로 감염된 MC3T3-E1 세포(골생성세포)에서 골 형성 인자인 RUNX2, BMP-2/4 및 OSX의 발현이 증가하는 것을 확인할 수 있다. As a result, referring to Figure 5, in MC3T3-E1 cells (osteogenic cells) infected with Porphyromonas gingivalis by SDF1δ-derived peptide S10 prepared in Example 1, the osteogenic factors RUNX2 and BMP-2/4 and OSX expression can be confirmed to increase.
더불어, 포르피로모나스 진지발리스 구강 감염에 의한 치조골 소실을 micro-CT를 이용하여 측정하여 정상 대조군과 비교한 결과, 도 6을 참조하면, 상기 S10이 포르피로모나스 진지발리스에 의한 치조골 소실을 억제하여 실험적 치주염 증상을 개선함을 확인할 수 있다.In addition, the alveolar bone loss caused by Porphyromonas gingivalis oral infection was measured using micro-CT and compared with the normal control group. Referring to Figure 6, the S10 showed alveolar bone loss caused by Porphyromonas gingivalis. It can be confirmed that the symptoms of experimental periodontitis are improved by suppressing it.
<실험예 4> 다양한 균에 감염된 THP-1 유래 대식세포에서의 항염증 효과 확인<Experimental Example 4> Confirmation of anti-inflammatory effect in THP-1 derived macrophages infected with various bacteria
상기 실시예 1에 따라 합성된 SDF1δ 유래 펩타이드 S10이 치주 질환과 관련된 균, 아그레가티박터 액티노마이세템코미탄스(Aggregatibacter actinomycetemcomitans, Aa), 퓨조박테리움 뉴클레아툼(Fusobacterium nucleatum, Fn), 스트렙토코쿠스 뮤탄스(Streptococcus mutans, Sm), 및 트레포네마 덴티콜라(Treponema denticola, Td)로 감염된 THP-1 유래 대식세포에서 항염증 효과를 가지는지 여부를 확인하였다. 상세 실험방법은 상기 실험예 1과 같다.The SDF1δ-derived peptide S10 synthesized according to Example 1 is a bacterium related to periodontal disease, Aggregatibacter actinomycetemcomitans (Aa), Fusobacterium nucleatum (Fn), It was confirmed whether THP-1 derived macrophages infected with Streptococcus mutans (Sm) and Treponema denticola (Td) have an anti-inflammatory effect. The detailed experimental method is the same as Experimental Example 1 above.
그 결과, 도 7에 나타난 바와 같이, 상기 균에 감염된 대식세포에 SDF1δ 유래 펩타이드 S10을 처리한 결과, TNF-α 값이 현저히 감소함을 확인할 수 있다.As a result, as shown in Figure 7, it can be seen that when macrophages infected with the above bacteria were treated with SDF1δ-derived peptide S10, the TNF-α value was significantly reduced.
이상 설명으로부터, 본 발명에 속하는 기술 분야의 당업자는 본 발명의 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며, 한정적인 것이 아닌 것으로서 이해해야만 한다.From the above description, those skilled in the art to which the present invention pertains will understand that the present invention can be implemented in other specific forms without changing its technical idea or essential features. In this regard, the embodiments described above should be understood in all respects as illustrative and not restrictive.
Claims (7)
A pharmaceutical composition for preventing or treating periodontal disease, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
상기 치주 질환은,
치은염(gingivitis), 치주염(periodontal inflammation), 치조골 파손(alveolar bone breakage) 및 치조골형성장애(alveolar bone osteodystrophy)로 이루어진 군으로부터 선택된 1종 이상인 것을 특징으로 하는, 치주 질환의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The periodontal disease is,
A pharmaceutical composition for the prevention or treatment of periodontal disease, characterized in that it is one or more selected from the group consisting of gingivitis, periodontal inflammation, alveolar bone breakage, and alveolar bone osteodystrophy. .
상기 치조골형성장애는,
치조골다공증(alveolar bone osteoporosis), 치조골연화증(alveolar bone osteomalacia) 및 치조골감소증(alveolar bone osteopenia)으로 이루어진 군으로부터 선택된 1종 이상인 것을 특징으로 하는, 치주 질환의 예방 또는 치료용 약학적 조성물.
According to claim 2,
The alveolar bone dysplasia is
A pharmaceutical composition for the prevention or treatment of periodontal disease, characterized in that it is one or more selected from the group consisting of alveolar bone osteoporosis, alveolar bone osteomalacia, and alveolar bone osteopenia.
상기 펩타이드는,
포르피로모나스 진지발리스(Porphyromonas gingivalis), 아그레가티박터 액티노마이세템코미탄스(Aggregatibacter actinomycetemcomitans), 퓨조박테리움 뉴클레아툼(Fusobacterium nucleatum), 스트렙토코쿠스 뮤탄스(Streptococcus mutans), 및 트레포네마 덴티콜라(Treponema denticola)로 이루어진 군에서 선택된 하나 이상의 발현을 억제하는 것을 특징으로 하는, 치주 질환의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The peptide is,
Porphyromonas gingivalis , Aggregatibacter actinomycetemcomitans , Fusobacterium nucleatum , Streptococcus mutans , and Tre A pharmaceutical composition for preventing or treating periodontal disease, characterized in that it inhibits the expression of one or more selected from the group consisting of Treponema denticola .
An oral composition for preventing or improving periodontal disease, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
A composition for oral external application for preventing or improving periodontal disease, comprising as an active ingredient a peptide consisting of the amino acid sequence of SEQ ID NO: 1.
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KR1020220119089A KR20240041381A (en) | 2022-09-21 | 2022-09-21 | Composition for the prevention or treatment of periodontal disease |
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KR1020220119089A KR20240041381A (en) | 2022-09-21 | 2022-09-21 | Composition for the prevention or treatment of periodontal disease |
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KR1020220119089A KR20240041381A (en) | 2022-09-21 | 2022-09-21 | Composition for the prevention or treatment of periodontal disease |
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR101759828B1 (en) | 2016-03-10 | 2017-07-20 | 경희대학교 산학협력단 | Composition for the prevention or treatment of periodontal disease |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR101759828B1 (en) | 2016-03-10 | 2017-07-20 | 경희대학교 산학협력단 | Composition for the prevention or treatment of periodontal disease |
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