KR102329670B1 - A composition improving of oral microbiome comprising heat-treated solar sea salt - Google Patents
A composition improving of oral microbiome comprising heat-treated solar sea salt Download PDFInfo
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- KR102329670B1 KR102329670B1 KR1020200044596A KR20200044596A KR102329670B1 KR 102329670 B1 KR102329670 B1 KR 102329670B1 KR 1020200044596 A KR1020200044596 A KR 1020200044596A KR 20200044596 A KR20200044596 A KR 20200044596A KR 102329670 B1 KR102329670 B1 KR 102329670B1
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- heat
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Abstract
본 발명은 열처리 가공염을 포함하는 구강내 균총 개선용 조성물에 관한 것으로 구강 내 바이오필름 형성균 및 치주염 유발균을 억제시킬 뿐만 아니라 장내 유익균으로 알려진 균을 구강내에서 증식시켜 구강 내 균총(microbiome)을 변화시킬 수 있다.The present invention relates to a composition for improving oral flora comprising heat-treated salt, which not only inhibits oral biofilm-forming bacteria and periodontitis-causing bacteria, but also proliferates bacteria known as beneficial intestinal bacteria in the oral cavity to improve oral microbiome. can change
Description
본 발명은 열처리 가공염을 포함하여 구강 내 바이오필름 형성균 및 치주염 유발균을 억제시킬 뿐만 아니라 장내 유익균으로 알려진 균을 구강내에서 증식시킴으로써 구강내 균총을 개선시킬 수 있는 조성물에 관한 것이다.The present invention relates to a composition capable of improving oral flora by not only inhibiting biofilm-forming bacteria and periodontitis-causing bacteria in the oral cavity, including heat treatment processed salt, but also proliferating bacteria known as beneficial intestinal bacteria in the oral cavity.
바이오필름(Biofilm)이란, 미생물에 의해 형성된 다양한 폴리머 물질로 싸인 미생물 복합체로 생물막 또는 균막 이라고도 불린다. 이러한 바이오필름은 미생물이 다양한 환경에 적응하는데 도움을 주는 보호막의 역할을 하며 바이오필름 내의 균체들은 서로 대사(metabolism)을 공유하기도 하고, 유전자 전달(gene transfer)을 통해 생존에 유리한 성질들을 획득하기도 한다. Biofilm is a microbial complex surrounded by various polymer materials formed by microorganisms, also called biofilm or biofilm. This biofilm acts as a protective film that helps microorganisms adapt to various environments, and the cells in the biofilm share metabolism with each other and acquire properties favorable for survival through gene transfer. .
따라서 바이오필름을 형성한 균체들은 일반적인 부유균 상태로 존재할 때 보다 가혹한 환경과 항생제에 대해 훨씬 강한 저항력을 가지며, 장기에 형성된 바이오필름은 다양한 병증을 야기한다. 이러한 병증이나 발병 위치를 예로 들면, 충치(dental caries), 치은염(gingivitis), 치주염(periodontitis), 중이염(otitis media), 인공후두(voice prostheses), 뇌수종(hydrocephalus hunts), 낭포성 섬유증(cystic fibrosis), 심내막염(valvular endocarditis), 인공심장판막(prosthetic heart valves), 중심정맥관(central venous catheter), 인공고관절(prosthetic hip joint), 인공슬관절(prosthetic knee joint), 만성 세균성 전립선염(chronic bacterial prostatitis), 자궁내 장치(intrauterine devices), 요도관(urinarycatheter) 등을 들 수 있다.Therefore, the cells that formed the biofilm have much stronger resistance to harsh environments and antibiotics than when they exist in the state of general airborne bacteria, and the biofilm formed in the organ causes various diseases. Examples of these conditions or locations of onset include dental caries, gingivitis, periodontitis, otitis media, voice prostheses, hydrocephalus hunts, cystic fibrosis. ), valvular endocarditis, prosthetic heart valves, central venous catheter, prosthetic hip joint, prosthetic knee joint, chronic bacterial prostatitis , intrauterine devices, and urinary catheters.
한편, 구강은 약 1,000여종의 세균이 존재하는 것으로 알려져 있으며, 이에 서식하는 많은 세균은 구강 바이오 필름을 형성한다. 그중 초기 구강 바이오필름 형성과 관련된 세균으로는 스트렙토코커스 종(Streptococcus spp.)으로 알려져 있다. 이들 스트렙토코커스 종은 치아표면의 초기 부착균으로, 특히 스트렙토코커스 고도니(Streptococcus gordonii), 스트렙토코커스 오랄리스(Streptococcus oralis)는 치석의 원인이 되는 구강 바이오필름의 형성이 시작되는데 중요한 역할을 한다. 또한, 포피로모나스 진지발리스(Porphyromonas gingivalis)는 치주염, 치은염과 같은 잇몸 질환을 유발하는 주요 원인균으로 알려져 있다. 따라서 치석 형성을 억제함에 있어 이들 균을 제어하고자 하는 노력이 지속되고 있다.On the other hand, it is known that about 1,000 kinds of bacteria exist in the oral cavity, and many bacteria inhabiting the oral cavity form an oral biofilm. Among them, the bacteria involved in the formation of an early oral biofilm are known as Streptococcus spp. These Streptococcus species are early adherent bacteria on the tooth surface, particularly Streptococcus gordonii and Streptococcus oralis ). In addition, Porphyromonas gingivalis ( Porphyromonas gingivalis ) is known as a major causative agent of gum disease such as periodontitis and gingivitis. Therefore, efforts to control these bacteria in suppressing the formation of calculus are continuing.
치아 표면에 형성된 바이오필름에 타액 내의 칼슘이나 마그네슘 등의 금속 이온이 결합되면 석회화된 치석을 형성하게 된다. 치석이 적절하게 제거되지 못하면 치은염, 치주염과 같은 잇몸 질환을 야기하며 심각하게는 치아의 손실을 유발한다. 치주질환의 발생을 예방하기 위한 노력으로 클로로헥시딘 글루코네이트, 세틸피리디움 클로라이드, 생귀나린 및 트리클로산과 같은 항균제가 개발되어 양치약 및 치약과 같은 구강제품에 적용되어 왔으나, 아직까지도 치주염의 발생을 근본적으로 예방하지 못하고 있는 실정이다. 또한 이러한 합성 항생제는 장기간 사용할 경우, 구강 내 점막을 자극할 뿐만 아니라, 정상균도 파괴시켜 오히려 구강 내 병원균에 대한 내성을 증가시키며, 치아착색 및 미각을 해치는 등의 인체에 대한 부작용이 크다.When metal ions such as calcium or magnesium in saliva are combined with the biofilm formed on the tooth surface, calcified calculus is formed. If the tartar is not removed properly, it causes gum diseases such as gingivitis and periodontitis, and seriously causes tooth loss. In an effort to prevent the occurrence of periodontal disease, antibacterial agents such as chlorhexidine gluconate, cetylpyridium chloride, sanguinarine and triclosan have been developed and applied to oral products such as toothpaste and toothpaste. is not fundamentally preventable. In addition, when these synthetic antibiotics are used for a long period of time, they not only stimulate the oral mucosa, but also destroy normal bacteria to increase resistance to pathogens in the oral cavity, and have great side effects on the human body, such as tooth discoloration and damage to taste.
따라서 합성 화합물을 사용하는 기존제품들의 문제점을 극복할 수 있는, 천연 항균제를 포함하는 구강내 균총 개선용 조성물 및 구강 질환 예방, 치료 또는 기선용 조성물이 요구된다.Therefore, there is a need for a composition for improving oral flora and a composition for preventing, treating or starting oral diseases, including a natural antibacterial agent, which can overcome the problems of existing products using synthetic compounds.
본 발명의 목적은 열처리 가공염을 포함하여 구강 내 바이오필름 형성균 및 치주염 유발균을 억제시킬 뿐만 아니라 장내 유익균으로 알려진 균을 구강내에서 증식시킴으로써 구강내 균총을 개선시킬 수 있는 조성물을 제공하는데 있다. An object of the present invention is to provide a composition capable of improving the oral flora by not only inhibiting biofilm-forming bacteria and periodontitis-causing bacteria in the oral cavity, including heat treatment processed salt, but also proliferating bacteria known as beneficial intestinal bacteria in the oral cavity.
또한, 본 발명의 다른 목적은 열처리 가공염을 포함하는 구강내 균총 개선용 약학 조성물을 제공하는데 있다.In addition, another object of the present invention is to provide a pharmaceutical composition for improving oral flora comprising a heat-treated salt.
또한, 본 발명의 또 다른 목적은 열처리 가공염을 포함하는 구강내 균총 개선용 식품 조성물을 제공하는데 있다.In addition, another object of the present invention is to provide a food composition for improving oral flora comprising a heat-treated salt.
또한, 본 발명의 또 다른 목적은 열처리 가공염을 유효성분으로 함유하는 구강 질환 예방 또는 개선용 구강 위생 조성물을 제공하는데 있다.In addition, another object of the present invention is to provide an oral hygiene composition for preventing or improving oral diseases containing heat-treated processed salt as an active ingredient.
상기한 목적을 달성하기 위한 본 발명의 구강내 균총 개선용 조성물은 황화수소가 방출되는 열처리 가공염을 유효성분으로 함유할 수 있다.The composition for improving oral flora of the present invention for achieving the above object may contain a heat-treated processed salt in which hydrogen sulfide is released as an active ingredient.
상기 약학 조성물은 바이오필름 형성균 및 치주염 유발균을 억제시킬 수 있다.The pharmaceutical composition may inhibit biofilm-forming bacteria and periodontitis-causing bacteria.
상기 바이오필름 형성균은 슈도알테로모나스(Pseudoalteromonas)속 및 포토박테리움(Photobacterium)속으로 이루어진 군에서 선택된 1종 이상일 수 있다(슈도알테로모나스(Pseudoalteromonas)속이 바이오필름 형성균이라는 것은 APPLIED AND ENVIRONMENTAL MICROBIOLOGY, June 2004, p. 3232-3238; ORIGINAL RESEARCH vol 8, Article 1822에 기재되어 있으며, 포토박테리움(Photobacterium)속이 바이오필름 형성균이라는 것은 Veterinary Microbiology 174 (2014) 247-254 ; Microbial Pathogenesis 69-70 (2014) 13-19에 기재되어 있다.)The biofilm-forming bacteria are Pseudoalteromonas genus and Picture tumefaciens may be at least one member selected from the group consisting in (Photobacterium) (pseudo Alteromonas (Pseudoalteromonas) lie is called biofilm forming bacteria APPLIED AND ENVIRONMENTAL MICROBIOLOGY, June 2004, p 3232-3238;. ORIGINAL RESEARCH
상기 치주염 유발균은 프레보텔라(Prevotella)속일 수 있다(프레보텔라(Prevotella)속이 치주염 유발균이라는 것은 Microbiome Deep Sequencing & Periodontal Disease vol 7, Issue 6, e37919; Functional &Integrative Genomics vol 17, 513-536(2017)에 기재되어 있다.)The periodontitis-induced bacteria frame beam telra (Prevotella) can lie (telra frame beam (Prevotella) lie is called gingivitis-induced bacteria Microbiome Deep Sequencing & Periodontal Disease vol 7 ,
상기 약학 조성물은 장내 유익균으로 알려진 균을 구강내에서 증식시킬 수 있으며, 상기 장내 유익균으로 알려진 균은 아커만시아(Akkermansia)속일 수 있다(아커만시아(Akkermansia)속이 장내 유익균이라는 것은 Microbial Pathogenesis 106(2017) 171-181; Scientific Reports vol 9, Article number: 15683 (2019)에 기재되어 있다.)The pharmaceutical composition is that only can be multiply the bacteria known as intestinal yuikgyun in the mouth, bacteria markers known in the intestinal yuikgyun cyano (Akkermansia) can lie (only markers cyano (Akkermansia) lie intestinal yuikgyun Microbial Pathogenesis 106 ( 2017) 171-181; Scientific Reports vol 9, Article number: 15683 (2019).
상기 황화수소가 방출되는 열처리 가공염은 1 g의 열처리 가공염을 기준으로 1000 내지 3000 ㎍의 황화수소가 방출될 수 있다.In the heat treatment processed salt from which hydrogen sulfide is released, 1000 to 3000 μg of hydrogen sulfide may be released based on 1 g of heat treatment processed salt.
상기 황화수소가 방출되는 열처리 가공염은 천일염을 대나무통에 충진시킨 후 600 내지 800 ℃로 열처리하는 과정을 2 내지 10회 반복하여 1차 소성시킨 다음 상기 1차 소성된 천일염을 대나무에 충진시킨 후 상기 1차 소성 시의 온도에 비하여 300 내지 500 ℃ 높은 온도에서 2차 소성시킨 것일 수 있다.The heat-treated processed salt in which the hydrogen sulfide is released is first calcined by repeating the process of heat-treating at 600 to 800 ° C. 2 to 10 times after filling a bamboo barrel with sea salt, and then filling the first calcined sea salt into the bamboo. The secondary firing may be performed at a
또한, 상기한 다른 목적을 달성하기 위한 본 발명의 구강내 균총 개선용 식품 조성물은 황화수소가 방출되는 열처리 가공염을 유효성분으로 함유할 수 있다.In addition, the food composition for improving oral flora of the present invention for achieving the above other object may contain a heat-treated processed salt in which hydrogen sulfide is released as an active ingredient.
또한, 상기한 다른 목적을 달성하기 위한 본 발명의 구강 질환 예방 또는 치료용 약학 조성물은 황화수소가 방출되는 열처리 가공염을 유효성분으로 함유할 수 있다.In addition, the pharmaceutical composition for preventing or treating oral diseases of the present invention for achieving the above other object may contain a heat-treated processed salt in which hydrogen sulfide is released as an active ingredient.
상기 구강 질환은 충치(dental caries), 치은염(gingivitis), 치주염(periodontitis), 구강내 점막 궤양, 구취(halitosis) 및 구강건조증(xerostomia)으로 이루어진 군에서 선택된 1종 이상일 수 있다.The oral disease may be at least one selected from the group consisting of dental caries, gingivitis, periodontitis, oral mucosal ulceration, halitosis, and xerostomia.
또한, 상기한 다른 목적을 달성하기 위한 본 발명의 구강 질환 예방 또는 개선용 구강 위생 조성물은 황화수소가 방출되는 열처리 가공염을 유효성분으로 함유할 수 있다.In addition, the oral care composition for preventing or improving oral diseases of the present invention for achieving the above other object may contain a heat-treated processed salt in which hydrogen sulfide is released as an active ingredient.
상기 구강 위생 조성물은 치약, 구강세정제, 구강청정제, 구강용 스프레이, 구강용 연고제, 구강용 바니쉬, 구강양치액 및 검으로 이루어진 군에서 선택된 1종 이상일 수 있다.The oral care composition may be at least one selected from the group consisting of toothpaste, mouthwash, mouthwash, oral spray, oral ointment, oral varnish, mouthwash, and gum.
본 발명의 구강내 균총 개선용 조성물은 황화수소가 방출되는 열처리 가공염을 유효성분으로 함유하여 바이오필름 형성균 및 치주염 유발균을 억제시킬 뿐만 아니라 장내 유익균으로 알려진 균을 구강내에서 증식시킬 수 있다.The composition for improving oral flora of the present invention contains heat-treated processed salts that release hydrogen sulfide as an active ingredient, thereby inhibiting biofilm-forming bacteria and periodontitis-causing bacteria, as well as proliferating bacteria known as beneficial intestinal bacteria in the oral cavity.
또한, 본 발명의 열처리 가공염을 함유한 조성물은 충치(dental caries), 치은염(gingivitis), 치주염(periodontitis), 구강내 점막 궤양, 구취(halitosis) 및 구강건조증(xerostomia)으로 이루어진 군에서 선택된 1종 이상의 구강 질환을 예방, 치료 또는 개선시킬 수 있다.In addition, the composition containing the heat treatment processed salt of the present invention is one selected from the group consisting of dental caries, gingivitis, periodontitis, oral mucosal ulceration, halitosis and xerostomia. It is possible to prevent, treat or ameliorate the above oral diseases.
또한, 본 발명은 천연물질로 이루어져서 합성 물질에 의한 부작용이나 위험도가 없는 인체에 안전한 조성물이므로 기능성 식품 조성물, 치약, 구강용 가글 등과 같이 인체에 직접 닿거나 심지어 인체에 들어가는 구강 위생 제품으로 다양하게 응용할 수 있다.In addition, the present invention is a composition that is safe for the human body because it is made of natural materials and has no side effects or risks caused by synthetic materials, so it can be applied to various oral hygiene products that directly contact the human body or even enter the human body, such as functional food compositions, toothpaste, oral gargles, etc. can
도 1은 치주염 유발을 위한 실험동물모델을 촬영한 사진이다.
도 2a는 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 치조골을 나타낸 사진이며, 도 2b는 상기 치조골의 CEJ-ABC거리를 나타낸 그래프이다.
도 3a는 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 파골세포 활성을 나타낸 사진이며, 도 3b는 도 3a의 파골세포 활성을 수치로 나타낸 그래프이다.
도 4는 정상군과 대조군의 구강내 미생물 조성을 다차원 척도법(Multi-Dimensional Scaling, MDS)으로 비교하여 나타낸 것이다.
도 5a는 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 미생물 조성을 다차원 척도법(Multi-Dimensional Scaling, MDS) 비교한 것이고, 도 5b 및 도 5c는 각 실험군들의 구강내 미생물 종류의 풍부성 및 다양성을 나타낸 것이다.
도 6은 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총을 문(phylum level)수준에 대한 상대적 풍부도(relative abundance)로 확인하여 나타낸 열지도(heatmap)이다.
도 7은 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총을 과(family level)수준에 대한 상대적 풍부도(relative abundance)로 확인하여 나타낸 열지도(heatmap)이다.1 is a photograph of an experimental animal model for inducing periodontitis.
Figure 2a is a photograph showing the alveolar bone of a normal group, a control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group mice, Figure 2b is a graph showing the CEJ-ABC distance of the alveolar bone.
Figure 3a is a photograph showing osteoclast activity of normal group, control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group mice, Figure 3b is a graph showing the osteoclast activity of Figure 3a numerically.
4 is a comparison of the oral microbial composition of the normal group and the control group by a multi-dimensional scaling method (Multi-Dimensional Scaling, MDS).
Figure 5a is a comparison of the oral microbial composition of the mice of the normal group, the control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group by a multi-dimensional scaling method (Multi-Dimensional Scaling, MDS), Figures 5b and 5c are each experimental group It shows the abundance and diversity of the types of microorganisms in their oral cavity.
6 is a heat map showing the oral flora of the mice of the normal group, the control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group by confirming the relative abundance with respect to the phylum level ( heatmap).
7 is a heat map showing the oral flora of the normal group, control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group mice as the relative abundance for the family level (relative abundance) ( heatmap).
본 발명은 열처리 가공염을 포함하여 구강 내 바이오필름 형성균 및 치주염 유발균을 억제시킬 뿐만 아니라 장내 유익균으로 알려진 균을 구강내에서 증식시킴으로써 구강내 균총을 개선시킬 수 있는 조성물에 관한 것이다.The present invention relates to a composition capable of improving oral flora by not only inhibiting biofilm-forming bacteria and periodontitis-causing bacteria in the oral cavity, including heat treatment processed salt, but also proliferating bacteria known as beneficial intestinal bacteria in the oral cavity.
또한, 본 발명은 열처리 가공염을 포함하여 구강 질환을 예방, 치료 또는 개선시킬 수 있는 조성물을 제공할 수 있다.In addition, the present invention may provide a composition capable of preventing, treating, or ameliorating oral diseases, including heat-treated processed salts.
상기 구강 질환은 구강 내 바이오필름 형성균 및 치주염 유발균에 의해 발생할 수 있는 질환인 것으로서, 바람직하게는 충치(dental caries), 치은염(gingivitis), 치주염(periodontitis), 구강내 점막 궤양, 구취(halitosis) 및 구강건조증(xerostomia)으로 이루어진 군에서 선택된 1종 이상을 들 수 있다.The oral disease is a disease that can be caused by biofilm-forming bacteria and periodontitis-causing bacteria in the oral cavity, and preferably, dental caries, gingivitis, periodontitis, mucosal ulcers in the oral cavity, and halitosis. ) and at least one selected from the group consisting of xerostomia.
이하, 본 발명을 상세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명의 조성물은 1 g의 열처리 가공염을 기준으로 1000 내지 3000 ㎍, 바람직하게는 1400 내지 2000 ㎍의 황화수소가 방출되는 열처리 가공염을 포함한다.The composition of the present invention comprises a heat-treated processed salt in which 1000 to 3000 μg, preferably 1400 to 2000 μg, of hydrogen sulfide is released, based on 1 g of the heat-treated processed salt.
상기 황화수소가 방출되는 열처리 가공염은 바이오필름 형성균 및 치주염 유발균을 억제시킬 뿐만 아니라 장내 유익균으로 알려진 균을 구강내에서 증식시킬 수 있다.The heat-treated processed salt in which the hydrogen sulfide is released can inhibit biofilm-forming bacteria and periodontitis-causing bacteria, as well as proliferate bacteria known as beneficial intestinal bacteria in the oral cavity.
상기 열처리 가공염에 의해 억제되는 바이오필름 형성균으로는 슈도알테로모나스(Pseudoalteromonas)속 및 포토박테리움(Photobacterium)속으로 이루어진 군에서 선택된 1종 이상을 들 수 있으며; 상기 치주염 유발균으로는 프레보텔라(Prevotella)속을 들 수 있다.The biofilm-forming bacteria inhibited by the heat treatment processing salt include Pseudoalteromonas genus and and at least one selected from the group consisting of the genus Photobacterium; The periodontitis-causing bacteria may include the genus Prevotella.
또한, 상기 열처리 가공염에 의해 증식되는 장내 유익균으로는 아커만시아(Akkermansia)속을 들 수 있다.In addition, beneficial intestinal bacteria proliferated by the heat treatment processed salt include Akkermansia genus.
상기 열처리 가공염이 방출하는 황화수소의 농도가 상기 하한치 미만인 경우에는 바이오필름 형성균 및 치주염 유발균을 억제시키지 못하고 장내 유익균으로 알려진 균의 구강내 증식을 촉진하지 못할 수 있으며, 상기 상한치 초과인 경우에는 장내 유익균으로 알려진 균이 구강내에서 증식하지 못하고 유해균에 대한 억제능이 감소될 수 있다.If the concentration of hydrogen sulfide emitted by the heat treatment processed salt is less than the lower limit, it may not be able to inhibit biofilm-forming bacteria and periodontitis-causing bacteria, and may not promote the growth of bacteria known as beneficial intestinal bacteria in the oral cavity. Bacteria known as beneficial bacteria cannot proliferate in the oral cavity, and the inhibitory ability against harmful bacteria may be reduced.
본 발명의 열처리 가공염은 용융된 열처리 가공염으로서, (a) 천일염을 대나무에 충진시킨 후 600 내지 800 ℃에서 3 내지 8시간 동안 가열시켜 1차 소성시키는 단계; (b) 상기 1차 소성된 천일염을 분쇄한 후 다시 대나무에 충진시킨 다음 상기 1차 소성 시의 온도에 비하여 300 내지 500 ℃ 높은 온도에서 2 내지 7시간 동안 가열시켜 2차 소성시키는 단계; 및 (c) 상기 2차 소성된 열처리된 가공염을 상온에서 냉각하는 단계;를 포함할 수 있다. 또한, 상기 (a)단계에서 천일염을 소성시킨 후 분쇄하여 다시 (a)단계의 조건으로 소성시키는 과정을 2 내지 10회 반복 수행함으로써 원하는 효과를 얻을 수 있다. The heat treatment processed salt of the present invention is a molten heat treatment processed salt, comprising the steps of: (a) filling bamboo with sea salt and then heating it at 600 to 800° C. for 3 to 8 hours for primary firing; (b) pulverizing the first calcined sea salt, filling the bamboo again, and then heating it at a
상기 (a)단계에서는 천일염을 대나무에 90 내지 99 부피%로 충진시킨 후 600 내지 800 ℃에서 3 내지 8시간, 바람직하게는 4 내지 5시간 동안 가열시킨 다음 분쇄시키고 다시 천일염을 대나무에 충진시켜 600 내지 800 ℃에서 3 내지 8시간 동안 가열시키는 과정을 2 내지 10회 반복한다.In step (a), after filling the bamboo with 90 to 99% by volume of sea salt, it is heated at 600 to 800° C. for 3 to 8 hours, preferably for 4 to 5 hours, and then pulverized, and the sea salt is again filled in the bamboo to 600 The process of heating at 800° C. for 3 to 8 hours is repeated 2 to 10 times.
상기 구운 천일염을 제조하기 위한 천일염은 국내산 천일염으로서, 수분함량이 7.0 내지 10.5%이며, 칼슘함량이 800 내지 1500 mg/kg, 칼륨함량이 1500 내지 3500 mg/kg 및 마그네슘함량이 6000 내지 12000 mg/kg인 것을 사용해야 상기 원하는 농도의 황화수소를 방출하는 열처리 가공염을 제조할 수 있다. 상기 국내산 천일염 대신 수분함량이 5.0 내지 5.1%이며, 칼슘함량이 900 내지 920 mg/kg, 칼륨함량이 1000 내지 1100 mg/kg 및 마그네슘함량이 4400 내지 4500 mg/kg인 중국산 천일염; 수분함량이 5.1 내지 5.2%이며, 칼슘함량이 750 내지 800 mg/kg, 칼륨함량이 800 내지 850 mg/kg 및 마그네슘함량이 3000 내지 3200 mg/kg인 베트남 및 일본산 천일염; 또는 수분함량이 0.5 내지 0.7%이며, 칼슘함량이 300 내지 350 mg/kg, 칼륨함량이 150 내지 200 mg/kg 및 마그네슘함량이 80 내지 100 mg/kg인 호주 및 멕시코산 천일염을 사용하는 경우에는 원하는 농도의 황화수소를 방출하는 열처리 가공염을 얻을 수 없다.The sea salt for preparing the grilled sea salt is domestic sea salt, with a moisture content of 7.0 to 10.5%, a calcium content of 800 to 1500 mg/kg, a potassium content of 1500 to 3500 mg/kg, and a magnesium content of 6000 to 12000 mg/kg. kg should be used to prepare a heat-treated processed salt that releases hydrogen sulfide at the desired concentration. Chinese sea salt having a water content of 5.0 to 5.1%, a calcium content of 900 to 920 mg/kg, a potassium content of 1000 to 1100 mg/kg, and a magnesium content of 4400 to 4500 mg/kg instead of the domestic sea salt; Sea salts from Vietnam and Japan having a water content of 5.1 to 5.2%, a calcium content of 750 to 800 mg/kg, a potassium content of 800 to 850 mg/kg, and a magnesium content of 3000 to 3200 mg/kg; Alternatively, when using Australian and Mexican sun-dried salt having a water content of 0.5 to 0.7%, a calcium content of 300 to 350 mg/kg, a potassium content of 150 to 200 mg/kg, and a magnesium content of 80 to 100 mg/kg, It is not possible to obtain heat-treated processing salts that release the desired concentration of hydrogen sulfide.
1차 소성 시 온도 및 시간이 상기 하한치 미만인 경우에는 원하는 농도의 황화수소를 방출하는 열처리 가공염을 제조할 수 없으며, 상기 상한치 초과인 경우에는 본 발명에서 원하는 효과가 저하될 수 있다. If the temperature and time during the primary firing are less than the lower limit, it is not possible to prepare a heat treatment processed salt emitting a desired concentration of hydrogen sulfide, and if it exceeds the upper limit, the desired effect in the present invention may be reduced.
또한, (a)단계를 반복적으로 수행하지 않는 경우에는 본 발명에서 원하는 효과를 얻을 수 없다.In addition, if step (a) is not repeatedly performed, the desired effect cannot be obtained in the present invention.
다음으로, 상기 (b)단계에서는 상기 1차 소성된 천일염을 대나무에 90 내지 99 부피%로 충진시킨 후 상기 1차 소성 시의 온도에 비하여 300 내지 500 ℃가 더 높은 온도에서 2 내지 7시간, 바람직하게는 4 내지 5시간 동안 가열시켜 2차 소성시킨다.Next, in step (b), after filling the bamboo with 90 to 99% by volume of the first calcined sun-dried salt, at a
2차 소성 시 온도 및 시간이 상기 하한치 미만인 경우에는 바이오필름 형성균 및 치주염 유발균을 억제시키지 못하고 장내 유익균으로 알려진 균의 구강내 증식을 촉진하지 못할 수 있으며, 상기 상한치 초과인 경우에는 원하는 효과를 전혀 얻을 수 없다.If the temperature and time during secondary firing are less than the lower limit, it may not be possible to inhibit biofilm-forming bacteria and periodontitis-causing bacteria, and it may not be possible to promote the growth of bacteria known as beneficial intestinal bacteria in the oral cavity. can't get it at all
2차 소성 시 온도를 1차 소성 온도보다 높임으로써 천일염을 용융시키는데, 상기 1차 소성 시 비용융된 천일염을 제조한 후 2차 소성 시 고온에서 용융된 천일염을 제조함으로써 원하는 농도의 황화수소를 얻을 수 있으며, 이에 따라 1차 소성된 천일염에 비하여 원하는 효과를 더욱 촉진시킬 수 있고 구강내 균총 변화를 더욱 향상시킬 수 있다. During the second calcination, the sea salt is melted by raising the temperature higher than the first calcination temperature. During the first calcination, unmelted sea salt is prepared, and then during the second calcination, hydrogen sulfide of a desired concentration can be obtained by preparing the molten sea salt at a high temperature. In this way, the desired effect can be further promoted compared to the primary calcined sea salt, and the change of the oral flora can be further improved.
본 명세서에서 용어 ‘유효성분으로 함유하는’이란 열처리 가공염의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 일예로, 상기 열처리 가공염은 10 내지 1500 mg/kg, 바람직하게는 20 내지 500 mg/kg의 농도로 사용된다. 열처리 가공염은 천연물로서 과량 투여하여도 인체에 부작용이 없으므로 본 발명의 조성물 내에 포함되는 열처리 가공염의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.As used herein, the term 'contained as an active ingredient' means including an amount sufficient to achieve the efficacy or activity of the heat-treated processed salt. For example, the heat treatment processed salt is used at a concentration of 10 to 1500 mg/kg, preferably 20 to 500 mg/kg. Since heat-treated processed salt is a natural product and has no adverse effects on the human body even when administered in excess, the upper limit of the quantity of heat-treated processed salt included in the composition of the present invention can be selected and implemented by those skilled in the art within an appropriate range.
본 발명의 구강 세정용 조성물은 구강 내 위생을 위한 치약, 구강용 세정제, 구강 청결제, 구강 스프레이, 구강 양치액 등의 제형으로 사용될 수 있으나, 이에 한정하는 것은 아니다.The composition for mouthwash of the present invention may be used in formulations such as toothpaste, mouthwash, mouthwash, oral spray, mouthwash, etc. for oral hygiene, but is not limited thereto.
상기 치약류는 연마제, 점결제, 보습제, 발포제, 감미료, 향미제 등의 성분을 하나 이상 포함할 수 있다. 치약류 중 페이스트상과 액상 구강용 조성물에서는 그 제조시 보습제로 솔비톨, 글리세린, 에틸렌글리콜, 프로필렌글리콜, 폴리에테르 글리콜, 폴리프로필렌 글리콜 등에서 1종 또는 2종 이상을 전체 조성물의 약 10 내지 70%의 양으로 배합하여 사용할 수 있다.The toothpaste may include one or more ingredients such as abrasives, binders, humectants, foaming agents, sweeteners, and flavoring agents. Among toothpastes, in paste-like and liquid oral compositions, one or two or more of sorbitol, glycerin, ethylene glycol, propylene glycol, polyether glycol, polypropylene glycol, etc. are used as a moisturizing agent in the preparation of about 10 to 70% of the total composition. It can be used in combination in quantities.
본 발명의 약제학적 조성물은 상기 유효 성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, a disintegrant, a sweetener, a binder, a coating agent, a swelling agent, a lubricant, A lubricant or flavoring agent may be used.
상기 약제학적 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다.The pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration.
상기 약제학적 조성물의 제제 형태는 과립제, 산제, 정제, 피복정, 캡슐제, 좌제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 등이 될 수 있다. 예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효 성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약제학적으로 허용 가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연 당, 옥수수 감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성 검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐 아세테이트, 소듐 클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸 셀룰로스, 아가, 벤토니트, 잔탄 검 등을 포함한다.Formulations of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectables. For formulation in the form of, for example, tablets or capsules, the active ingredient may be combined with an orally, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or required, suitable binders, lubricants, disintegrants and color-developers may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.In the composition formulated as a liquid solution, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostats may be added as needed. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to form an injectable formulation such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules or tablets.
더 나아가 해당분야의 적절한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.Furthermore, by using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA by an appropriate method in the art, it can be preferably formulated according to each disease or component.
본 발명의 약제학적 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration. .
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현예에 따르면, 본 발명의 약제학적 조성물의 1일 투여량은 0.001-10 g/㎏이다.A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration mode, age, weight, sex, morbidity, food, administration time, administration route, excretion rate and response sensitivity of the patient, An ordinarily skilled physician can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001-10 g/kg.
본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be prepared in a unit dose form by formulating using a pharmaceutically acceptable carrier and/or excipient, or may be prepared by internalizing in a multi-dose container. In this case, the formulation may be in the form of a solution, suspension, or emulsion in oil or an aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.
또한, 본 발명은 열처리 가공염을 유효성분으로 함유하는 구강내 균총 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for improving oral flora containing heat treatment processed salt as an active ingredient.
본 발명에 따른 식품 조성물은 상기 약제학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 알코올 음료류, 과자류, 다이어트바, 유제품, 육류, 초코렛, 피자, 라면, 기타 면류, 껌류, 아이스크림류, 비타민 복합제, 건강보조식품류 등이 있다.The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, sweets, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gums, ice cream, vitamin complexes, health supplements etc.
본 발명의 식품 조성물은 유효성분으로서 열처리 가공염뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 본 발명의 열처리 가공염 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종 식물 추출액 등을 추가로 포함시킬 수 있다.The food composition of the present invention may include not only heat-treated salt as an active ingredient, but also ingredients commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatine, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink or beverage, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be additionally included in addition to the heat treatment processed salt of the present invention.
본 발명은 상기 열처리 가공염을 유효성분으로 포함하는 구강내 균총 개선용 식품 조성물을 포함하는 건강기능식품을 제공한다. 건강기능식품이란, 열처리 가공염을 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용시 발생할 수 있는 부작용 등이 없는 장점이 있다. 이와 같이 하여 얻어지는 본 발명의 건강기능식품은, 일상적으로 섭취하는 것이 가능하기 때문에 매우 유용하다. 이와 같은 건강기능식품에 있어서의 열처리 가공염의 첨가량은, 대상인 건강기능식품의 종류에 따라 달라 일률적으로 규정할 수 없지만, 식품 본래의 맛을 손상시키지 않는 범위에서 첨가하면 되며, 대상 식품에 대하여 통상 0.01 내지 50 중량%, 바람직하기로는 0.1 내지 20 중량%의 범위이다. 또한, 환제, 과립제, 정제 또는 캡슐제 형태의 건강기능식품의 경우에는 통상 0.1 내지 100 중량% 바람직하기로는 0.5 내지 80 중량%의 범위에서 첨가하면 된다. 한 구체예에서, 본 발명의 건강기능식품은 환제, 정제, 캡슐제 또는 음료의 형태일 수 있다.The present invention provides a health functional food comprising a food composition for improving oral flora comprising the heat treatment processed salt as an active ingredient. Health functional food refers to food prepared by adding heat-treated salt to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspension, etc. However, unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long period of time by using food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be ingested on a daily basis. The amount of heat treatment processed salt added in such health functional food varies depending on the type of health functional food and cannot be defined uniformly, but it can be added within a range that does not impair the original taste of the food, and is usually 0.01 for the target food. to 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of a health functional food in the form of pills, granules, tablets or capsules, it is usually added in an amount of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.
또한, 본 발명은 구강내 균총 개선용 의약 또는 식품의 제조를 위한 열처리 가공염의 용도를 제공한다. 상기한 바와 같이 열처리 가공염은 구강내 균총 개선을 위한 용도로 이용될 수 있다.In addition, the present invention provides the use of a heat-treated processed salt for the manufacture of a medicament or food for improving oral flora. As described above, the heat treatment processed salt can be used for the purpose of improving the flora in the oral cavity.
또한, 본 발명은 포유동물에게 유효량의 열처리 가공염을 투여하는 것을 포함하는 구강내 균총 개선 방법을 제공한다.The present invention also provides a method for improving oral flora, comprising administering to a mammal an effective amount of a heat-treated processed salt.
여기에서 사용된 용어 "포유동물"은 치료, 관찰 또는 실험의 대상인 포유동물을 말하며, 바람직하게는 인간을 말한다.As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation or experimentation, preferably a human.
여기에서 사용된 용어 "유효량"은 연구자, 수의사, 의사 또는 기타 임상의에 의해 생각되는 조직계, 동물 또는 인간에서 생물학적 또는 의학적 반응을 유도하는 유효 성분 또는 약학적 조성물의 양을 의미하는 것으로, 이는 해당 질환 또는 장애의 증상의 완화를 유도하는 양을 포함한다. 본 발명의 유효 성분에 대한 유효량 및 투여횟수는 원하는 효과에 따라 변화될 수 있다. 그러므로, 투여될 최적의 투여량은 당업자에 의해 쉽게 결정될 수 있으며, 질환의 종류, 질환의 중증도, 조성물에 함유된 유효성분 및 다른 성분의 함량, 제형의 종류, 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 본 발명의 예방, 치료 또는 개선 방법에 있어서, 성인의 경우, 열처리 가공염을 1일 1회 내지 수회 투여시, 0.001 g/kg 내지 10 g/kg의 용량으로 투여하는 것이 바람직하다.As used herein, the term “effective amount” refers to the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human as conceived by a researcher, veterinarian, physician or other clinician, which an amount that induces amelioration of the symptoms of a disease or disorder. The effective amount and frequency of administration for the active ingredient of the present invention may vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of the active ingredient and other components contained in the composition, the type of formulation, and the age, weight, and general health of the patient It can be adjusted according to various factors including condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, and concurrently used drugs. In the prevention, treatment, or improvement method of the present invention, for adults, it is preferable to administer the heat-treated processed salt at a dose of 0.001 g/kg to 10 g/kg when administered once to several times a day.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시하나, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명의 범주 및 기술사상 범위 내에서 다양한 변경 및 수정이 가능함은 당업자에게 있어서 명백한 것이며, 이러한 변형 및 수정이 첨부된 특허청구범위에 속하는 것도 당연한 것이다.Hereinafter, preferred examples are presented to aid the understanding of the present invention, but the following examples are merely illustrative of the present invention and it will be apparent to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention, It goes without saying that such variations and modifications fall within the scope of the appended claims.
실시예 1. 열처리 가공염Example 1. Heat treatment processed salt
전라남도 신안군에서 생산된 1년 묵은 갯벌 천일염(수분함량: 7.2%이며, 칼슘함량: 864 mg/kg, 칼륨함량: 1769 mg/kg, 마그네슘함량: 6468 mg/kg)을 4년생의 대나무에 99 부피%로 충진하고 밀봉한 후, 700 ℃의 온도에서 5시간 동안 가열한 후 상기 가열된 소금을 분쇄한 다음 상기 분쇄된 천일염을 상기와 동일한 방법 즉, 대나무에 충진하고 가열하는 과정을 7회 반복하여 동일한 과정을 총 8회 반복하여 1차 소성을 수행하였다. 상기 1차 소성된 천일염을 다시 대나무에 99 부피%로 충진하고 밀봉한 후 1100℃의 온도에서 5시간 동안 가열하여 2차 소성을 수행하여 자색을 지닌 열처리 가공염을 수득하였다.One-year-old tidal flat sun-dried salt (moisture content: 7.2%, calcium content: 864 mg/kg, potassium content: 1769 mg/kg, magnesium content: 6468 mg/kg) produced in Sinan-gun, Jeollanam-do was added to 4-year-old bamboo by 99 volumes. %, after heating at 700 ° C. for 5 hours, grinding the heated salt, and repeating the same method as above, that is, filling and heating bamboo with the crushed sea salt 7 times. The same process was repeated a total of 8 times to perform primary firing. The first calcined sea salt was again filled with 99 vol% of bamboo, sealed, and heated at 1100° C. for 5 hours to perform secondary calcination to obtain a heat-treated processed salt having a purple color.
비교예 1. 일반 소금 사용Comparative Example 1. Use of regular salt
미네랄이 함유되지 않은 일반 소금을 사용하였다.Ordinary salt without minerals was used.
비교예 2. 천일염 사용 Comparative Example 2. Use of sea salt
천일염으로 수분함량이 5.01%이며, 칼슘함량이 920 mg/kg, 칼륨함량이 1042 mg/kg, 마그네슘함량이 4490 mg/kg인 천일염을 사용하였다.Sea salt with a water content of 5.01%, a calcium content of 920 mg/kg, a potassium content of 1042 mg/kg, and a magnesium content of 4490 mg/kg was used.
<시험예><Test Example>
시험예 1. 황화수소 함량 확인Test Example 1. Confirmation of hydrogen sulfide content
실시예 1, 비교예 1 및 2에 따라 제조된 열처리 가공염 0.1 g을 각각 증류수 10 mL로 용해한 다음 2분 동안 원심분리하여 불용성 물질을 제거하고 시료용액을 제조하였다. 제조된 시료용액 430 μL에 생리식염수 50 μL를 혼합한 후 1% zinc acetate 용액 250 μL과 증류수 250 μL를 가한 다음 20 mM N,N-dimethyl-p-phenylendediamine sulfate가 함유된 7.2 M HCl 용액 133 μL과 30 mM FeCl3가 함유된 1.2 M HCl 용액 133 μL를 첨가하여 상온에서 5분간 반응시켰다. 상기 반응용액을 96 웰 마이크로플레이트 리더(96 well microplate reader)를 이용하여 650 nm에서 흡광도를 측정하였다. 또한, 표준물질 NaHS(3.125-200 μM)으로 표준곡선을 작성한 다음 이를 이용하여 열처리 가공염으로부터 생성되는 황화수소 함량을 구하였다.0.1 g of the heat-treated processed salt prepared according to Example 1, Comparative Examples 1 and 2 was dissolved in 10 mL of distilled water, respectively, and then centrifuged for 2 minutes to remove insoluble substances and a sample solution was prepared. Mix 50 µL of physiological saline with 430 µL of the prepared sample solution, add 250 µL of 1% zinc acetate solution and 250 µL of distilled water, and then 133 µL of 7.2 M HCl solution containing 20 mM N , N- dimethyl- p-phenylendediamine sulfate and 133 μL of 1.2 M HCl solution containing 30 mM FeCl 3 and reacted at room temperature for 5 minutes. Absorbance of the reaction solution was measured at 650 nm using a 96 well microplate reader. In addition, a standard curve was prepared with the standard material NaHS (3.125-200 μM), and the content of hydrogen sulfide generated from heat-treated processed salt was calculated using this.
위 표 1에 나타낸 바와 같이, 본 발명의 실시예 1에 따라 제조된 열처리 가공염은 1 g 당 1500±100 μg의 황화수소를 생성하며, 비교예 1 및 2는 황화수소를 생성하지 않는 것을 확인하였다.As shown in Table 1 above, it was confirmed that the heat-treated processed salt prepared according to Example 1 of the present invention produced 1500±100 μg of hydrogen sulfide per 1 g, and Comparative Examples 1 and 2 did not produce hydrogen sulfide.
동물실험animal testing
실험동물은 8주령의 정상쥐(Male Wistar rats, 체중 250 ± 20 g)를 오리엔트바이오에서 구입하여 사용하였고, 상대습도 55±5%, 온도 25±1 ℃, 조명주기 12시간(06:00~18:00)으로 설정되어 있는 사육실에서 일반 사료(Zeigler사의 Rodent NIH-31 제품)로 1주일 동안 적응시킨 후 체중을 측정한 다음, 난괴법에 의해 각 실험군을 n=8로 나누어 실험을 실시하였다.As the experimental animals, 8-week-old normal rats (Male Wistar rats, weight 250 ± 20 g) were purchased from Orient Bio and used, relative humidity 55±5%, temperature 25±1 ℃, lighting cycle 12 hours (06:00~ 18:00) in a breeding room set to normal feed (Rodent NIH-31 product by Zeigler) for 1 week, then the weight was measured, and then each experimental group was divided into n=8 by the egg mass method. .
-마우스--mouse-
정상군: 치실 생략 + 식염수 Normal group: floss omitted + saline solution
대조군: 치실 + 1% CMC(carboxymethyl cellulose) 용액으로 양치Control: brush teeth with dental floss + 1% CMC (carboxymethyl cellulose) solution
비교예 1군: 치실 + 비교예 1의 일반소금(NaCl 기준으로 20 중량%)이 함유된 1% CMC 용액으로 양치Comparative Example 1 Group: Brush teeth with 1% CMC solution containing dental floss + general salt of Comparative Example 1 (20% by weight based on NaCl)
비교예 2군: 치실 + 비교예 2의 천일염(NaCl 기준으로 20 중량%)이 함유된 1% CMC 용액으로 양치 Comparative Example 2 Group: Brush teeth with dental floss + 1% CMC solution containing the sea salt of Comparative Example 2 (20% by weight based on NaCl)
실시예 1군: 치실 + 실시예 1의 열처리 가공염(NaCl기준으로 20 중량%)이 함유된 1% CMC 용액으로 양치Example 1 group: dental floss + brushing teeth with 1% CMC solution containing the heat treatment salt of Example 1 (20% by weight based on NaCl)
상기 각 실험군을 대상으로 펜토바르비탈(엔토발, HANLIM PHARM., LTD, Korea) 50 mg/kg을 복강 내 주사하여 마취시킨 다음 도 1과 같이 마우스의 좌, 우측 상악 제2 대구치의 치경부에 치실을 묶어 미생물 점착을 유도함으로서 치주염을 유발시켰다. 치주염을 유발시키는 8주 동안 상악과 하악 협측을 각각의 상기 각 군의 용액으로 10회씩 문질러 양치시켰다.For each experimental group, 50 mg/kg of pentobarbital (Entobal, HANLIM PHARM., LTD, Korea) was injected intraperitoneally to anesthetize, and then floss the cervical region of the left and right maxillary second molars of the mouse as shown in FIG. 1 . periodontitis was induced by binding microbial adhesion. For 8 weeks of inducing periodontitis, the maxilla and the mandibular buccal were brushed by rubbing each of the solutions of each group 10 times.
시험예 2. 치조골 소실 정도 측정Test Example 2. Measurement of alveolar bone loss
실험 8주째에 종료 후 상악 우측 대구치 부분을 분리하여 4% paraformaldehyde 고정액에 24시간 고정한 다음 멸균하였다. 멸균한 상악 조직을 2.6% 차아염소산나트륨 용액에서 세척하고 정제수로 3회 추가 세척한 다음 70% 에탄올에 보관하였다. 이후 0.3 % 메틸렌 블루 용액에 침지시켜 5분 동안 염색시키고 치조골 소실 정도를 평가하였다. 치조골 소실 정도는 상악 두 번째 대구치 뿌리 축을 치아의 시멘트질(cementoenamel junction, CEJ) 경계에서 에나멜질(alveolar bone crest, ABC) 까지의 거리로 측정하였다.After completion of the experiment on the 8th week, the upper and right molars were separated, fixed in 4% paraformaldehyde fixative for 24 hours, and then sterilized. The sterilized maxillary tissue was washed in 2.6% sodium hypochlorite solution, washed three more times with purified water, and then stored in 70% ethanol. Then, it was immersed in 0.3% methylene blue solution and stained for 5 minutes, and the degree of alveolar bone loss was evaluated. The degree of alveolar bone loss was measured as the distance from the cementoenamel junction (CEJ) boundary of the maxillary second molar root axis to the alveolar bone crest (ABC).
도 2a는 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 치조골을 나타낸 사진이며, 도 2b는 상기 치조골의 CEJ-ABC거리를 나타낸 그래프이다.Figure 2a is a photograph showing the alveolar bone of the mice of the normal group, the control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group, and Figure 2b is a graph showing the CEJ-ABC distance of the alveolar bone.
도 2a 및 도 2b에 도시된 바와 같이, CEJ-ABC거리는 정상군이 360.9±8.0 μm, 대조군이 632.9±15.6 μm, 비교예 1군이 607.4±22.7 μm, 비교예 2군이 534.1±28.1 μm, 실시예 1군이 499.7±23.0 μm로 측정되었다.2a and 2b, the CEJ-ABC distance was 360.9±8.0 μm in the normal group, 632.9±15.6 μm in the control group, 607.4±22.7 μm in the comparative example 1 group, 534.1±28.1 μm in the comparative example 2 group, Example 1 group was measured to be 499.7±23.0 μm.
치주염 유발군(대조군, 실시예 1군, 비교예 1군 및 비교예 2군)들의 경우에는 정상군에 비해 치조골 소실정도가 길어 치주염이 유발되었음을 알 수 있었고, 비교예 1군의 경우 대조군과 유사할 정도로 치조골이 소실되었으며, 비교예 2군과 실시예 1군의 경우 비교예 1군에 비해 치조골 소실이 낮은 것을 확인하였다. 특히, 실시예 1군이 다른 군에 비하여 치조골 소실이 가장 낮은 것을 확인하였다.In the case of periodontitis-inducing groups (control group, Example 1 group, Comparative Example 1 group, and Comparative Example 2 group), it was found that periodontitis was induced because the degree of alveolar bone loss was longer than that of the normal group, and Comparative Example 1 group was similar to the control group. Alveolar bone was lost to the extent that it was found, and in the case of Comparative Example 2 and Example 1, the loss of alveolar bone was lower than in Comparative Example 1 group. In particular, it was confirmed that Example 1 group had the lowest loss of alveolar bone compared to other groups.
이러한 결과는 실시예 1군의 처리가 치주염에 의한 치조골 소실을 예방할 수 있다는 것을 의미한다.These results indicate that the treatment of Example 1 group can prevent alveolar bone loss due to periodontitis.
시험예 3. 치주조직에서 파골세포 활성 평가Test Example 3. Evaluation of osteoclast activity in periodontal tissue
실험 8주째에 종료 후 상악 우측 대구치 부분을 분리하여 4% paraformaldehyde에 48시간 고정한 다음 10% EDTA 용액에서 2주 동안 탈칼슘화시켰다. 이후 에탄올 70 중량%, 95 중량%, 100 중량% 용액에서 순차적으로 탈수시키고 100 중량% 자일렌(xylene) 용액으로 처리과정을 거친 다음 파라핀으로 포매하여 7 μm 두께로 절편하였다. 절편된 조직 내로 자일렌을 처리한 다음 에탄올로 수화시키고 증류수로 세척하였다. 이후 슬라이드를 0.1 M sodium acetate, 80 mM L-(+) Tartaric acid, 50 mM glacial acetic acid(pH 5.0)과 기질인 naphthol AS-MX phosphate이 포함된 버퍼용액에서 37 ℃로 30분간 처리하였다. 처리한 슬라이드는 증류수로 세척한 다음 mounting medium(봉입제)를 넣고 덮개유리를 씌워 광학 현미경으로 관찰하였다.After completion of the experiment at the 8th week, the upper and right molars were separated and fixed in 4% paraformaldehyde for 48 hours, and then decalcified in 10% EDTA solution for 2 weeks. After that, it was sequentially dehydrated in 70% by weight, 95% by weight, and 100% by weight of ethanol, treated with a 100% by weight xylene solution, and then embedded in paraffin and sectioned to a thickness of 7 μm. After xylene was treated into the sectioned tissue, it was hydrated with ethanol and washed with distilled water. Thereafter, the slides were treated in a buffer solution containing 0.1 M sodium acetate, 80 mM L-(+) tartaric acid, 50 mM glacial acetic acid (pH 5.0), and naphthol AS-MX phosphate as a substrate at 37 °C for 30 minutes. The treated slides were washed with distilled water, then a mounting medium (encapsulant) was added, and a cover glass was covered and observed with an optical microscope.
도 3a는 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 파골세포 활성을 나타낸 사진이며, 도 3b는 도 3a의 파골세포 활성을 수치로 나타낸 그래프이다. 즉, TRAP 염색법을 이용하여 각 실험군의 상악 제2 대구치 원심면과 치근 이개부위의 치근 흡수와 치조골 흡수를 관찰한 것이다. Figure 3a is a photograph showing osteoclast activity of normal group, control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group mice, Figure 3b is a graph showing the osteoclast activity of Figure 3a numerically. That is, root resorption and alveolar bone resorption were observed in the distal surface of the maxillary second molar and distal surface of the maxillary second molar in each experimental group using the TRAP staining method.
골조직은 파골세포와 조골세포로 구성되어 있는데 뼈리모델링(bone remodeling) 과정에서 파골세포는 골을 흡수하며, 조골세포는 흡수된 부위에서 필요한 양의 골을 형성하여 일정한 골의 형태를 유지시키는 것으로 알려져 있다.Bone tissue is composed of osteoclasts and osteoblasts. In the process of bone remodeling, osteoclasts absorb bone, and it is known that osteoblasts maintain a certain bone shape by forming a required amount of bone at the absorbed site. have.
한편, 치주염은 치아의 소실을 야기하는 주요 질병인 동시에 치주염 유발 치조골 흡수를 수반하는 질병으로 알려져 있으며, 치주염 진행과정에서 함께 일어나는 파골세포의 비정상적인 과활성은 치주염 유발을 확인할 수 있는 인자이므로 파골세포 활성을 측정하였다.On the other hand, periodontitis is known as a major disease causing tooth loss and a disease accompanying periodontitis-induced alveolar bone resorption. was measured.
도 3a 및 도 3b에 도시된 바와 같이, 파골세포 활성정도는 대조군, 비교예 1군 > 비교예 2군 > 실시예 1군 > 정상군의 순서인 것을 확인하였다.As shown in FIGS. 3A and 3B , the degree of osteoclast activity was confirmed in the order of the control group, Comparative Example 1 group > Comparative Example 2 group > Example 1 group > Normal group.
예컨대, 치주염을 유발 후 실시예 1군에서는 다른 치주염 유발군(대조군, 비교예 1군 및 비교예 2군)에 비해 붉은색으로 염색된 TRAP 양성 다핵세포의 수와 면적이 감소한 것을 확인하였다. For example, after inducing periodontitis, it was confirmed that the number and area of TRAP-positive multinuclear cells stained in red were reduced in Example 1 group compared to other periodontitis-inducing groups (control group, Comparative Example 1 group and Comparative Example 2 group).
각 실험군에서 파골세포 활성을 조사한 결과 실시예 1군이 치주염에 의한 파골세포 형성을 억제하는데 긍정적인 영향을 준 것으로 판단된다. As a result of examining osteoclast activity in each experimental group, it is determined that Example 1 group had a positive effect on suppressing osteoclast formation due to periodontitis.
시험예 4. 구강내 균총(미생물 조성, oral microbiome) 분석Test Example 4. Oral flora (microorganism composition, oral microbiome) analysis
식이 8주째에 상악 협측면(buccal surface)을 면봉으로 문지른 다음 head 부분을 잘라 DNA extraction kit[QLAamp DNA Stool Mini Kit(Cat # 51504, Qiagen, USA)]를 이용하여 박테리아 DNA를 추출하였다. 완전한 상태의 DNA는 아가로스 겔(agarose gel) 전기영동을 전개하고 분석 전까지 -20 ℃에서 보관하였다.At the 8th week of the diet, the buccal surface of the maxilla was rubbed with a cotton swab, and the head was cut off to extract bacterial DNA using a DNA extraction kit [QLAamp DNA Stool Mini Kit (Cat # 51504, Qiagen, USA)]. The intact DNA was subjected to agarose gel electrophoresis and stored at -20 °C until analysis.
실험군들의 상악에서 처리한 면봉에서 추출한 DNA의 16S rRNA 과변 부위 중 V4를 PCR에 의해 증폭시키고, MiSeq library 제작은 2-step PCR을 이용하여 준비하였으며 MiSeq(illumina, Inc.) 플렛폼을 이용한 sequencing은 마크로젠(Macrogen Inc., Seoul, Republic of Korea)에서 수행하였다.Among the 16S rRNA hypervariable regions of the DNA extracted from the cotton swabs of the experimental groups, V4 was amplified by PCR, the MiSeq library was prepared using 2-step PCR, and sequencing using the MiSeq (illumina, Inc.) platform was performed by Macrogen. (Macrogen Inc., Seoul, Republic of Korea).
MiSeq 데이터는 대용량 서열 분석 도구모음인 Mothur 프로그램을 이용하여 서열 분석을 시행하였으며 chimera. uchime 명령어를 이용하여 키메라 서열을 확인하고 제거하였다. 얻어진 염기 서열의 길이가 짧거나 길어 염기쌍들이 일치되지 않을 경우에는 pre.cluster Mothur subroutine을 이용하여 수정하고 Silva 데이터베이스를 이용하여 정렬하였다. 염기서열의 분류는 greengene 데이터베이스(version 13.5.99)를 이용하고, 진핵 생물(eukaryote), 남세균(cyanobacteria), 미토콘드리아(mitochondria)는 제거한 후 분류학적 동정을 수행하였다.MiSeq data were sequenced using the Mothur program, a large-scale sequencing tool suite, and chimera. Chimeric sequences were identified and removed using the uchime command. If the length of the obtained nucleotide sequence was short or long and the base pairs did not match, it was corrected using the pre.cluster Mothur subroutine and aligned using the Silva database. The classification of the base sequence was performed using the greengene database (version 13.5.99), and after removing eukaryotes, cyanobacteria, and mitochondria, taxonomic identification was performed.
클러스터링 분석은 Vesearch, 미생물 군집 간 다양성 분석은 Bray-Curtis distance, 속 분류는 LEfSe, 16S rRNA 유전자 서열의 대사기능 예측은 PICRUSt, 다양한 대사 기능의 분리를 위해 STAMP를 이용하여 각 실험군 간 구강 미생물 다양성을 비교 분석하였다.For clustering analysis, Vesearch, for diversity analysis between microbial communities, Bray-Curtis distance, for genus classification, LEfSe, for prediction of metabolic function of 16S rRNA gene sequence, PICRUSt, and for separation of various metabolic functions, STAMP was used to determine oral microbial diversity between each experimental group. Comparative analysis was performed.
도 4는 정상군과 대조군의 구강내 미생물 조성을 다차원 척도법(Multi-Dimensional Scaling, MDS)으로 비교하여 나타낸 것이다.Figure 4 is a comparison of the composition of the oral microorganisms in the oral cavity of the normal group and the control group (Multi-Dimensional Scaling, MDS) is shown.
또한, 도 5a는 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 미생물 조성을 다차원 척도법(Multi-Dimensional Scaling, MDS) 비교한 것이고, 도 5b 및 도 5c는 각 실험군들의 구강내 미생물 종류의 풍부성 및 다양성을 나타낸 것이다.In addition, Figure 5a is a comparison of the composition of the oral microorganisms in the oral cavity of the normal group, the control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group (Multi-Dimensional Scaling, MDS), Figures 5b and 5c are It shows the abundance and diversity of the types of microorganisms in the oral cavity of each experimental group.
도 4에 도시된 바와 같이, 치주염 유발로 인하여 정상군과 대조군 간의 구강내 미생물 조성(oral microbiome)이 확연히 전환되었음을 알 수 있다. As shown in FIG. 4 , it can be seen that the oral microbiome between the normal group and the control group was significantly changed due to the induction of periodontitis.
또한 도 5a 내지 도 5c에 도시된 바와 같이, 치주염 유발군 중에서 대조군과 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군) 간에도 미생물 조성(oral microbiome)이 변화된 것을 확인하였다. 특히, 도 5b의 chao 지표를 보면 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)들의 미생물은 약 300~500종이었고 소금을 사용하지 않은 정상군과 대조군은 약 2000종 이상이었다. In addition, as shown in Figures 5a to 5c, it was confirmed that the microbial composition (oral microbiome) was changed even between the control group and the salt treatment group (Example 1 group, Comparative Example 1 group, and Comparative Example 2 group) among the periodontitis-inducing group. In particular, looking at the chao index of FIG. 5b, the microorganisms in the salt treatment group (Example 1 group, Comparative Example 1 group, and Comparative Example 2 group) were about 300 to 500 types, and the normal group and control group without salt were about 2000 types. It was more than that.
이러한 결과를 종합해보면 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)과 소금 비처리군(정상군 및 대조군) 간의 구강내 미생물 조성(oral microbiome)은 변화되었고, 특히 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)에서는 구강내 미생물이 줄어드는 것을 확인하였다.Combining these results, the oral microbiome between the salt-treated group (Example 1 group, Comparative Example 1 group, and Comparative Example 2 group) and the salt untreated group (normal group and control group) was changed, and in particular, salt In the treatment group (Example 1 group, Comparative Example 1 group and Comparative Example 2 group), it was confirmed that the microorganisms in the oral cavity were reduced.
시험예 5. 분류체계(Taxonomy)에 따른 구강내 균총(미생물 조성, oral microbiome) 비교 분석Test Example 5. Comparative analysis of oral flora (microorganism composition, oral microbiome) according to taxonomy
도 6은 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총을 문(phylum level)수준에 대한 상대적 풍부도(relative abundance)로 확인하여 나타낸 열지도(heatmap)이다. 6 is a heat map ( heatmap).
도 6에 도시된 바와 같이, 정상군과 대조군은 프로테오박테리아(Proteobacteria)가 증가한 반면, 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)은 일반적으로 장내 미생물로 알려진 퍼미큐티스(Firmicutes) 및 박테로이데테스(Bacteroidetes)가 증가한 것을 확인하였다. The normal group and the control group was of proteobacteria (Proteobacteria) is increased, whereas, the salt-treated group (Example group 1, Comparative Example 1 group and Comparative Example Group 2), as shown in Figure 6 is commonly known as the intestinal microflora permeation Firmicutes And Bacteroidetes ( Bacteroidetes ) It was confirmed that the increase.
특히, 실시예 1군은 주로 퍼미큐티스(Firmicutes)로 구성되며 비교예 1군 및 비교예 2군은 퍼미큐티스(Firmicutes) 및 박테로이데테스(Bacteroidetes)가 거의 동일한 비율로 구성되어 있는 것을 확인하였다.In particular, Example 1 group is mainly composed of Firmicutes , Comparative Example 1 and Comparative Example 2 groups are Firmicutes ( Firmicutes ) And Bacteroidetes ( Bacteroidetes ) It was confirmed that it is composed of almost the same ratio.
따라서, 도 5b의 Chao 분석에서 종 풍부도가 2000에서 500으로 감소한 것으로 보아 소금 처리에 의해 감소된 미생물 종은 대부분 프로테오박테리아(Proteobacteria)인 것으로 사료된다. Therefore, it is considered that most of the microbial species reduced by the salt treatment are Proteobacteria , as it is seen that the species abundance is reduced from 2000 to 500 in the Chao analysis of FIG. 5b .
도 7은 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총을 과(family level)수준에 대한 상대적 풍부도(relative abundance)로 확인하여 나타낸 열지도(heatmap)이다.7 is a heat map showing the oral flora of normal group, control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group mice as a relative abundance for the family level (relative abundance) ( heatmap).
도 7에 도시된 바와 같이, 비교예 1군 및 비교예 2군의 경우에는 미생물 군집이 유사한 경향을 보였으며, 각 실험군들에서 구체적으로 많이 나타나는 family 종이 관찰되었다. As shown in Figure 7, in the case of Comparative Example 1 group and Comparative Example 2 group, the microbial community showed a similar tendency, and a family species appearing specifically in each experimental group was observed.
시험예 6. 정상군과 소금 처리군들의 구강내 균총(미생물 조성, oral microbiome) 비교 분석Test Example 6. Comparative analysis of oral flora (microorganism composition, oral microbiome) of the normal group and the salt-treated group
하기 [표 2]에 정상군, 대조군, 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총을 속(genus level)수준에 대한 상대적 풍부도(relative abundance)로 확인하여 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)에서 감소되는 미생물을 나타내었다.In [Table 2] below, the oral flora of the mice of the normal group, the control group, Example 1 group, Comparative Example 1 group and Comparative Example 2 group was confirmed as the relative abundance with respect to the genus level and salt In the treatment group (Example 1 group, Comparative Example 1 group, and Comparative Example 2 group) was shown to be reduced microorganisms.
위 표 2에서 나타낸 바와 같이, 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)과 소금으로 처리하지 않은 정상군 간의 미생물 군집이 다르게 나타났고, 실시예 1군에서는 바이오필름(biofilm)을 형성하는 것으로 알려져 있는 슈도알테로모나스(Pseudoalteromonas)와 포토박테리움(Photobacterium)이 감소되어 열처리 가공염의 처리가 바이오필름(biofilm) 형성에 관여하는 미생물의 생성을 억제시켜 주는 것으로 판단된다. As shown in Table 2 above, the microbial community was different between the salt-treated group (Example 1 group, Comparative Example 1 group, and Comparative Example 2 group) and the normal group not treated with salt, and in Example 1 group, the biofilm Pseudomonas is known to form the (biofilm) Al Tero Pseudomonas (Pseudoalteromonas) It is determined that the photobacterium is reduced, so that the treatment of the heat treatment processing salt suppresses the generation of microorganisms involved in the formation of a biofilm.
하기 표 3은 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총을 속(genus level)수준에 대하여 상대적 풍부도(relative abundance)로 확인하고 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)들에서 증가되는 미생물을 나타낸 것이다.Table 3 below confirms the oral flora of Example 1 group, Comparative Example 1 group and Comparative Example 2 group mice as relative abundance with respect to the genus level, and the salt treatment group (Example 1 group) , Comparative Example 1 and Comparative Example 2) shows the increased microorganisms.
위 표 3에 나타낸 바와 같이, 소금 처리군(실시예 1군, 비교예 1군 및 비교예 2군)에서는 일반적인 장내 미생물로 알려져 있는 박테로이드(Bacteroides)속, 코프로코커스(Coprococcus)속, 락토바실러스(Lactobacillus)속, 오실로스피라(Oscillospira)속, 루미노코커스((R)Ruminococcus)속과 같은 미생물들이 증가한 것을 확인하였다. 특히, 소금 처리군들 중 비교예 1군은 치주염을 유발한다고 알려져 있는 프레보텔라(Prevotella)속이 증가하는 것으로 관찰되어 비교예 1군이 구강내 치주염 유발이 증가했던 상기 결과와 일치하였다. As shown in Table 3 above, in the salt treatment group (Example 1 group, Comparative Example 1 group and Comparative Example 2 group), Bacteroides genus , Coprococcus genus , Lactose known as common intestinal microorganisms it was confirmed that the bacillus (Lactobacillus), An oscilloscope Spira (Oscillospira), A luminometer Caucus ((R) Ruminococcus) in the microorganisms, such as an increase. In particular, in Comparative Example 1 among the salt treatment groups, the genus Prevotella , which is known to cause periodontitis, was observed to increase, which coincided with the above result that the induction of periodontitis in the oral cavity was increased in Comparative Example 1 group.
실시예 1군은 장에서 점질물질을 형성하며 장내 환경에 도움을 주는 유익균으로 알려져 있는 아커만시아(Akkermansia)속이 증가하는 것을 확인하였다. 최근 보고에 의하면 oral-gut axis에 의해 구강과 장내 미생물이 서로 상관관계를 갖는데(FEMS Microbiology Reviews, fuy035, 43, 2019, 1-18; Protein Cell 2018, 9(5):488-500; Flemer B, et al. Gut 2018;67:1454-1463), 본 발명의 연구결과에서 실시예 1군 처리 시 장에 도움을 주는 유익균이 구강에서도 발견되는 것을 확인하였다. 즉 소금 처리군 간에도 증가하거나 감소하는 미생물이 다르며 미네랄이 없는 일반소금으로 처리(비교예 1군) 시 구강내 유해균이 증가하고 열처리 가공염 처리(실시예 1군)은 유익균을 증가시켜주는 것을 확인하였다.In Example 1 group, it was confirmed that the genus Akkermansia , which is known as beneficial bacteria that forms a viscous material in the intestine and helps the intestinal environment, increases. According to a recent report, oral and intestinal microflora are correlated with each other by the oral-gut axis ( FEMS Microbiology Reviews , fuy035, 43, 2019, 1-18; Protein Cell 2018, 9(5):488-500; Flemer B , et al. Gut 2018;67:1454-1463), in the study results of the present invention, it was confirmed that beneficial bacteria helpful in the treatment of Example 1 group were also found in the oral cavity. That is, the microorganisms that increase or decrease even between the salt treatment groups are different, and when treated with general salt without minerals (Comparative Example 1 group), harmful bacteria in the oral cavity increased, and it was confirmed that the heat treatment processed salt treatment (Example 1 group) increased beneficial bacteria. .
시험예 7. 소금 처리군 간의 구강내 균총(미생물 조성, oral microbiome) 비교 분석Test Example 7. Comparative analysis of oral flora (microorganism composition, oral microbiome) between salt treatment groups
하기 표 4는 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총 차이를 문(phylum), 과(family), 속(genus) 수준에 대하여 상대적 풍부도(relative abundance)로 확인하고 비교예 1군에 비해 실시예 1군 및 비교예 2군에서 감소되는 미생물에 대하여 나타내었다.Table 4 below shows the differences in oral flora of Example 1, Comparative Example 1, and Comparative Example 2 mice as relative abundance for phylum, family, and genus levels. Confirmed and shown with respect to the microorganisms reduced in Example 1 group and Comparative Example 2 group compared to Comparative Example 1 group.
위 표 4에 나타낸 바와 같이, 속(genus level)수준에서 분류된 미생물 중 치주염을 유발하는 원인균으로 알려져 있는 프레보텔라(Prevotella)속이 실시예 1군 및 비교예 2군에서 감소한 것을 확인하였다.As shown in Table 4 above, it was confirmed that among the microorganisms classified at the genus level, the genus Prevotella , which is known as the causative bacteria causing periodontitis, was reduced in the Example 1 group and the Comparative Example 2 group.
따라서 실시예 1군 및 비교예 2군은 치주염 유발균 프레보텔라(Prevotella)속을 감소시킴으로서 구강 내 미생물 변화에 긍정적인 영향을 주고 치주염을 예방할 수 있는 구강 환경에 도움을 주는 것으로 사료된다. Therefore, it is considered that Example 1 and Comparative Example 2 groups have a positive effect on microbial changes in the oral cavity by reducing the periodontitis-causing bacteria Prevotella genus, and help the oral environment to prevent periodontitis.
하기 표 5는 실시예 1군, 비교예 1군 및 비교예 2군 마우스의 구강내 균총 차이를 문(phylum), 과(family), 속(genus) 수준에 대하여 상대적 풍부도(relative abundance)로 확인하고 비교예 1군에 비해 실시예 1군 및 비교예 2군에서 증가되는 미생물에 대하여 나타내었다.Table 5 below shows the differences in oral flora of Example 1, Comparative Example 1, and Comparative Example 2 mice as relative abundance for phylum, family, and genus levels. Confirmed and shown with respect to the microorganisms increased in Example 1 group and Comparative Example 2 group compared to Comparative Example 1 group.
위 표 5에 나타낸 바와 같이, 속(genus level)수준까지 분류된 미생물 중 장내 유익균으로 알려져 있는 아커만시아(Akkermansia)속이 비교예 2군에 비하여 실시예 1군이 더 증가한 것을 확인하였다. As shown in Table 5 above, it was confirmed that the genus Akkermansia , which is known as beneficial intestinal bacteria among microorganisms classified up to the genus level, increased in Example 1 group compared to Comparative Example 2 group.
즉, 치주염을 유발한 상태에서 실시예 1군은 치주염 유발균을 감소시키고 장내 유익균으로 알려진 균을 구강내에서 증가시키는 것으로 판단된다.That is, in the state inducing periodontitis, Example 1 group is determined to decrease periodontitis-causing bacteria and increase the bacteria known as beneficial intestinal bacteria in the oral cavity.
하기에 본 발명의 분말을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, formulation examples of the composition containing the powder of the present invention will be described, but the present invention is not intended to limit the present invention, but merely to describe it in detail.
제제예 1. 산제의 제조Formulation Example 1. Preparation of powder
실시예 1에서 얻은 열처리 가공염 500 mg500 mg of heat-treated processed salt obtained in Example 1
유당 100 mg
탈크 10 mgtalc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight bag to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2. Preparation of tablets
실시예 1에서 얻은 열처리 가공염 300 mg300 mg of heat-treated processed salt obtained in Example 1
옥수수전분 100 mg100 mg cornstarch
유당 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above ingredients, tablets are prepared by tableting according to a conventional manufacturing method of tablets.
제제예 3. 캅셀제의 제조Formulation Example 3. Preparation of capsules
실시예 1에서 얻은 열처리 가공염 200 mg200 mg of heat-treated processed salt obtained in Example 1
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mg0.2 mg magnesium stearate
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled in a gelatin capsule to prepare a capsule.
제제예 4. 주사제의 제조Formulation Example 4. Preparation of injection
실시예 1에서 얻은 열처리 가공염 600 mg600 mg of heat-treated processed salt obtained in Example 1
만니톨 180 mgmannitol 180 mg
주사용 멸균 증류수 2974 mg2974 mg of sterile distilled water for injection
Na2HPO4,12H2O 26 mgNa 2 HPO 4, 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플 당 상기의 성분 함량으로 제조한다.According to a conventional method for preparing injections, the content of the above ingredients per 1 ampoule is prepared.
제제예 5. 액제의 제조Formulation Example 5. Preparation of liquid formulation
실시예 1에서 얻은 열처리 가공염 4 g4 g of heat-treated processed salt obtained in Example 1
이성화당 10 g10 g isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water appropriate amount
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100g으로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to a conventional liquid preparation method, each component is added to purified water to dissolve, an appropriate amount of lemon flavor is added, the above components are mixed, purified water is added, the whole is adjusted to 100 g by adding purified water, and then filled in a brown bottle and sterilized to prepare a liquid.
제제예 6. 과립제의 제조Formulation Example 6. Preparation of granules
실시예 1에서 얻은 열처리 가공염 1,000 mg1,000 mg of heat-treated processed salt obtained in Example 1
비타민 혼합물 적량appropriate amount of vitamin mixture
비타민 A 아세테이트 70 ㎍70 μg vitamin A acetate
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mgVitamin B2 0.15 mg
비타민 B6 0.5 mg0.5 mg of vitamin B6
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 mgVitamin C 10 mg
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 mg1.7 mg of nicotinic acid amide
엽산 50 ㎍50 μg folic acid
판토텐산 칼슘 0.5 mgCalcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture appropriate amount
황산제1철 1.75 mgferrous sulfate 1.75 mg
산화아연 0.82 mgZinc Oxide 0.82 mg
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgpotassium phosphate monobasic 15 mg
제2인산칼슘 55 mgDicalcium Phosphate 55 mg
구연산칼륨 90 mgPotassium citrate 90 mg
탄산칼슘 100 mg100 mg of calcium carbonate
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 과립제에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 과립제 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.The composition ratio of the vitamin and mineral mixture is relatively suitable for granules in a preferred embodiment, but the mixing ratio may be arbitrarily modified. It can be prepared and used in the preparation of a health functional food composition according to a conventional method.
제제예 7. 기능성 음료의 제조Formulation Example 7. Preparation of functional beverage
실시예 1에서 얻은 열처리 가공염 1,000 mg1,000 mg of heat-treated processed salt obtained in Example 1
구연산 1,000 mg1,000 mg citric acid
올리고당 100 g100 g of oligosaccharides
매실농축액 2 g2 g of plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 mLAdd purified water to total 900 mL
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 기능성 음료 조성물 제조에 사용한다. After mixing the above ingredients according to the usual health drink manufacturing method, after stirring and heating at 85 ° C for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, then refrigerated. It is used to prepare the functional beverage composition of the present invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is prepared by mixing ingredients suitable for relatively favorite beverages in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and national preferences such as demand class, demanding country, and use.
제제예 7. 기능성 치약Formulation Example 7. Functional toothpaste
실시예 1에서 얻은 열처리 가공염 0.01 중량%0.01 wt% of the heat treatment processed salt obtained in Example 1
실리카 20.0 중량%Silica 20.0 wt%
농글리세린(98%) 30.0 중량%Concentrated glycerin (98%) 30.0 wt%
비결정성 소르비톨액(70%) 30.0 중량%Amorphous sorbitol solution (70%) 30.0 wt%
라우릴황산나트륨 1.0 중량%1.0 wt% sodium lauryl sulfate
카르복시메틸셀룰로오스나트륨 0.5 중량%0.5 wt% sodium carboxymethylcellulose
잔탄검 0.3 중량%0.3% by weight of xanthan gum
불화나트륨 0.22 중량%0.22 wt% sodium fluoride
향료 1.0 중량%Perfume 1.0% by weight
사카린나트륨 1.0 중량%1.0 wt% sodium saccharin
구연산 적량appropriate amount of citric acid
탄산수소나트륨 2.0 중량%Sodium bicarbonate 2.0 wt%
정제수 잔량Purified water remaining
상기 구강 조성물 중 치약 조성물의 제조 순서는 습윤제인 비결정성 소르비톨액에 카르복시메틸셀룰로오스나트륨, 사카린나트륨 등 분말 소량 성분을 분산시키고 정제수로 묽힌 다음 혼합기에서 1차 혼합하고, 그 다음에 실리카 및 탄산칼슘 등의 연마제를 넣고 2차 혼합했다. 그리고 마지막으로 기포제, 안정제, 향료 등을 넣고 3차 혼합함으로써 치약 조성물을 제조하였다.The order of preparation of the toothpaste composition in the oral composition is to disperse a small amount of powdered ingredients such as sodium carboxymethylcellulose and sodium saccharin in an amorphous sorbitol solution that is a wetting agent, dilute it with purified water, and first mix in a mixer, then silica and calcium carbonate, etc. of the abrasive was added and mixed secondarily. And finally, a toothpaste composition was prepared by adding a foaming agent, a stabilizer, a flavoring agent, and the like and third mixing.
Claims (13)
According to claim 12, wherein the oral care composition is toothpaste, mouthwash, mouthwash, oral spray, oral ointment, oral varnish, oral gargle, oral disease prevention, characterized in that at least one selected from the group consisting of gum or an oral hygiene composition for improvement.
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