불소의 대안, 나노 메디칼 하이드록시아파타이트, 아파프로란?

COMPANY MILESTONES 회사가 걸어온 발자취

1974	Sangi Co., Ltd. established in Tokyo

1978	Subsidiary Dental Kagaku Co., Ltd. established to produce hydroxyapatite First laboratory facility, Tochigi Prefecture

1980	Second R&D laboratory, Saitama Prefecture World’s first hydroxyapatite remineralizing toothpaste ”Apadent” launched

1985	Subsidiary Apatite Co., Ltd. established to handle sales Success of anticaries field trials among Japanese schoolchildren Second toothpaste brand ”Apagard” launched

1993	Sangi’s proprietary hydroxyapatite approved as an active anticaries ingredient, “Medical Hydroxyapatite,” by the Japanese government

1995	Sangi and its two subsidiaries merged Blockbuster TV commercial series boosts sales of Apagard, which briefly captures 20% market share

1996	Relocation and expansion of Saitama R&D laboratory

2003	Medical Hydroxyapatite reduced to 2-figure nanoparticle size, enhancing remineralization and restorative whitening capability

2004	“Renamel” brand launched exclusively for the dental route

2005	Sangi awarded a 2-year grant from Japan's New Energy and Industrial Technology Development Organization (NEDO) for its hydroxyapatite catalyst development (ethanol to butanol)

2007	Sangi's 70th hydroxyapatite-related patent registered

2009	ISO 9001:2000 certification Sangi online Shop opened

2010	Sangi receives a 4-year grant from the Japan Science and Technology Agency (JST) for its powder jet deposition project, a next-generation hydroxyapatite-based dental therapy system under development with Tohoku University

2011	Commencement of toothpaste exports to Russia (Apadent) (later also Apagard)

2013	Commencement of toothpaste exports to Canada (OEM brand)

2014	Company 40th anniversary celebrations Apagard’s 20th successive year as top-selling brand in Japan’s high-end “beauty whitening” toothpaste market segment

2015	ISO 13485 certification Commencement of toothpaste exports to Singapore and China (Apagard, Apadent) Apagard Premio awarded the inaugural No.1 Dental Product ranking by Japan's top consumer product-ranking site @cosme

MEDICAL HYDROXYAPATITE 의료용 하이드록시아파타이트

PRODUCT HISTORY

1980S

• World’s first *enamel-restorative
  

  *nanoparticle
  *hydroxyapatite toothpaste
  (‘Apadent’ 1980)

• Field trials among Japanese schoolchildren:
  36-56% reduction new caries in over 3 years
  

  (‘Apagard’ 1985)

1990S

• Active ingredient approved as an anticaries agent, ‘Medical Hydroxyapatite’(‹mHAP› ), in Japan.
  
• Sangi's nanohydroxyapatite patented worldwide

2000S

• Particle-size reduced from 3- to 2-figure nanoscale, increasing remineralizing effect
• Growing interest worldwide in nanohydroxyapatite
  

  *first European toothpastes launched
  *new dental applications developed
  (‘Renamel’ 2004, ‘Nanotect’ 2009)

  
  
• Medical Hydroxyapatite movie (produced in 2004)

1970s Born in Japan: A Toothpaste that Repairs Tooth Enamel 에나멜 수복용 치약개발

Japanese company Sangi first became interested in hydroxyapatite – the substance of our teeth and bone – after acquiring a dental materials patent from the U.S. National Aeronautics and Space Authority (NASA) in the 1970s. Astronauts lose mineral from their teeth and bone in a gravity-free environment, and NASA proposed synthesizing hydroxyapatite as a means of restoring this.

Sangi conceived the idea of enamel-restorative toothpaste using hydroxyapatite – the same substance as our teeth – in 1978, and launched the world's first nanohydroxyapatite toothpaste (‘Apadent’), using Sangi's own technology, in 1980. Sangi's enamel-restorative toothpastes now stretch to a wide range of brands (chiefly ‘Apagard,’ launched in 1985), and have been used extensively in Japan for their anticaries and whiteness-enhancing properties for over 30 years, with over 120 million tubes sold.

1980s Early Lab Work and Field Trials 초기 연구와 필드테스트

Throughout the 1980s, both in its own research and third-party studies commissioned at Japanese universities, Sangi accumulated data supporting the enamel-restorative properties of its proprietary nanohydroxyapatite ingredient. Most were reported in Japanese, but studies in English include those by Kani et al, The Effect of Apatite-Containing Dentifrices on Artificial Caries Lesions (1988) and Ohashi et al, Remineralization of Artificial Caries Lesions by Hydroxyapatite (1991), both of which were commissioned by Sangi and used Sangi's material. (See Research Papers).

Field trials were also conducted in separate locations involving over 1000 Japanese primary schoolchildren. Researchers from Tokyo Medical and Dental University and Gifu Dental University (now Asahi University) found children using Sangi's nanohydroxyapatite toothpaste at school under supervision once a day over a period of years developed significantly less caries than those using an identical toothpaste not containing hydroxyapatite. In some groups, the difference was as great as 36-56% reduction in new tooth decay.

1990s Anticaries Approval: Medical Hydroxyapatite(‹mHAP› ®) 충치예방물질 승인

Following over a decade of laboratory research and field trials, Sangi's proprietary form of hydroxyapatite was approved by the Japanese government as an active anticaries ingredient in 1993.

It was officially designated ‘Medical Hydroxyapatite’ (‹mHAP›) to distinguish it from other types of hydroxyapatite used in dental applications, such as dental abrasives. In contrast, Sangi's ingredient is non-abrasive, and repairs microscopic defects in surface and subsurface tooth enamel, restoring mineral density and therefore translucence to the enamel, and reversing incipient caries, the beginning of tooth decay.

Before 2003 After 2003

Nano ‹mHAP› particle size distribution
(Data: Sangi Central Research Laboratory)

2000s Emerging Interest in Nanohydroxyapatite Worldwide 나노하이드록시아파타이트에 대한 세계적인 관심

Sangi's hydroxyapatite, in oral care, is used mainly in toothpaste and remineralizing chewing gum. It has been shown to occlude exposed dentinal tubules, helping reduce hypersensitivity, and is also used in enamel-restorative formulations for dental clinical use.

Other applications now under development by Sangi include a home-care anticaries system targeting oral mutans streptococci reduction developed, in conjunction with the Japanese National Institute of Infectious Diseases, and a hydroxyapatite powder jet deposition system (PJD) for restorative dental treatment applications, in conjunction with Tohoku University.

In recent years, widespread interest has arisen in the restorative applications of nanohydroxyapatite pioneered by Sangi over the last three decades. Chemical companies BASF and Henkel,in Europe, both announced development of nanoparticle hydroxyapatite as a promising dentifrice ingredient in 2002, and Henkel launched the first European toothpaste to contain nanohydroxyapatite some years after. Many companies have now entered the field and a wide range of hydroxyapatite toothpastes is now available.

THE ALTERNATIVE ANTICARIES AGENT 충치예방물질의 대안

HYDROXYAPATITE

• safe
• biocompatible
• edible
• enamel-restorative
• anticariogenic
• a crystalline form of calcium phosphate
• as effective as fluoride

Safe A key Component of Human Body 인체이 주 구성성분

Hydroxyapatite is a major component of the human body, comprising 60% of bone, 97% of tooth enamel and 70% of dentin. Saliva is also rich in the components of hydroxyapatite, which it supplies to the teeth to replace mineral dissolved by plaque acids, the first step towards tooth decay.By restoring lost mineral, saliva acts to protect against decay in a natural healing process known as ‘remineralization.’ Sangi’s Medical Hydroxyapatite supports this natural healing function,

Biocompatible Used Widely in Dental & Medical Applications 치과와 의료용으로 널리 사용

Because it is extremely biocompatible, hydroxyapatite is used in a wide range of medical and dental applications, such as artificial tooth and bone, tissue repair, and coatings to improve the biocompatibility of orthopedic implants. It is also a protein-binding agent, used in chromatography and bacterial culture. In dental applications, hydroxyapatite is sometimes used as an abrasive,depending on its manufactured properties and particle size. However Sangi’s nanohydroxyapatite is a non-abrasive, enamel-restorative mineral, closely resembling the natural hydroxyapatite of the teeth, and approved in Japan for its anticaries properties.

Edible A Dietary Calcium Phosphate Source 음용가능한 칼슘포스페이트의 원료

Hydroxyapatite is also a rich source of easily digested calcium phosphate, and is used in dietary supplements, remineralizing chewing gum, and as an additive in foods.

Enamel-Restorative An Alternative to Fluoride for Anticaries Use 에나멜 수복: 불소의 대안

The influence of fluoride in reducing dental caries has been clearly demonstrated. Its use in drinking water and oral care products dates back over 70 years. Fluoridation has been called the single most effective public health measure to prevent new tooth decay, and early U.S. studies showed it reduced caries among schoolchildren by as much as 35-60%. However excess fluoride can lead to problems such as dental or skeletal fluorosis, and the amount permitted in oral care products and community water systems is controlled.

In contrast, nano Medical Hydroxyapatite, used as a remineralizing agent in toothpaste in Japan for the last three decades, was shown in field trials leading to its approval as an active anticaries ingredient to cause a similar reduction in new caries among schoolchildren to that seen with fluoridation in the U.S., namely 36-56%.(Fig 1.T.KANI et al Effect to Apatite-containing Dentifricres on Dental Caries in school Children)

　

Fig 1. Average increase in new caries using the test toothpaste once daily for 1 year (Group A) and 3 years (Group B)Fig 2. Remineralization effect of fluoride and nanohydroxyapatite toothpastes, by pH cycling

A recent in situ study conducted among healthy adults in the U.S. found that Sangi’s Medical Hydroxyapatite toothpaste not only inhibited development of caries but was not significantly different from fluoride in its ability to remineralize early caries lesions. (Amaechi et al, Remineralization of Early Caries Lesions by Nanohydroxyapatite Dentifrice). This supported the findings of earlier in vitro studies in Hong Kong which showed no significant difference in remineralizing effect between fluoride- and Medical Hydroxyapatite (‹mHAP ›)-containing toothpastes. (NM King et al, Remineralization by Nanohydroxyapatite-containing Dentifirice)

Moreover, hydroxyapatite has been shown to be safe – even edible – and can be swallowed by children without concern, as it has no known toxic or harmful impact.

Action of Fluoride 불소의 작용기전

Fluoride is an element (F-), supplied in the form of compounds such as sodium fluoride (NaF) or sodium monofluorophosphate (NaMFP). It does not replace mineral itself, but strengthens teeth against decay by promoting the uptake of calcium and phosphate from saliva and other sources into the enamel (remineralization). In doing so, it forms a new substance, fluoridated apatite, on the tooth surface, more resistant to plaque acids than the enamel’s original carbonated hydroxyapatite.
Fluoride is also said to impede bacterial metabolism, helping to lower the level of cariogenic bacteria in the mouth.

Action of Medical Hydroxyapatite 하이드록시아파타이트의 작용기전

In contrast, nano Medical Hydroxyapatite is a crystalline calcium phosphate substance almost identical to the natural hydroxyapatite of our teeth. Supplied in the form of nanoparticles, it directly replaces lost mineral to restore subsurface demineralized areas of tooth enamel (incipient caries) and fill microscopic fissures on the enamel surface. Its nanoparticles also bind protein such as oral bacteria and plaque fragments during brushing, facilitating their removal from the mouth.
Unlike fluoride, nano Medical Hydroxyapatite adds nothing ‘new’ to the enamel, and is less resistant to acid attack than fluoridated apatite, though more resistant than carbonated apatite. But Medical Hydroxyapatite achieves the same degree of remineralization as fluoride, as seen above, and penetrates to the very bottom of demineralized lesions, whereas fluoride tends to create a dense zone of fluoridated apatite at the top.
And by restoring the enamel’s mineral density and surface smoothness, Medical Hydroxyapatite increases resistance to bacterial attachment and therefore plaque development and tooth decay, at the same time enhancing the translucency, gloss and whiteness of the teeth.

CONSUMER BENEFITS 소비자의 혜택

Restoring mineral to the teeth~ Medical Hydroxyapatite Movie ~

Learn about Sangi's original nano-hydroxyapatite remineralizing technology and its oral care functions;

 

Copyright © 2016 SANGI CO.,LTD. All Rights Reserved.

  

Model of Action on the Teeth

<mHAP> nanoparticles

• adhere to and help remove bacteria & plaque
• fill and repair microscopic surface fissures
• remineralize subsurface demineralized areas
  (incipient caries)
  
• supplement salivary mineral
• occlude exposed dentinal tubules

Consumer Benefits

• protection against caries
• enhanced whiteness and gloss
• smoother enamel
• greater resistance to plaque and stains
• relief from hypersensitivity

Remineralization Natural Tooth Repair 재광화: 치아의 자연치유력

Sangi’s idea in developing the first nanohydroxyapatite remineralizing toothpaste was to support a naturally occurring function – the restorative role of saliva – in the mouth.
Demineralization and remineralization of tooth enamel take place constantly. The tooth surface is easily colonized by bacteria to form dental plaque, especially in minute fissures or spaces between the teeth where a toothbrush cannot reach. Enamel is made up of closely packed hydroxyapatite rods, separated by tiny channels about 50 nanometers wide. Acids produced by plaque bacteria seep into these channels and can dissolve the rods, causing the enamel to become demineralized.

Saliva plays a protective role, by neutralizing acids caused by plaque bacteria, and by providing calcium and phosphate ions – the building blocks of hydroxyapatite – which diffuse back into the enamel to restore lost mineral, so that the enamel becomes remineralized.

If demineralization and remineralization balance each other at the tooth surface, no net loss of mineral occurs. But conditions such as excess plaque, inadequate saliva flow, or heavy intake of acidic foods and beverages can tip the balance in favor or demineralization, so that a cavity – dental caries – may result.
However in its early stages, if sufficient mineral is provided, demineralization (incipient caries or ‘white spot’ lesions) can be reversed.
Nano supplements this natural supply of mineral by the saliva.

Anticaries Functions Mode of Action of nano <mHAP> 충치예방기능: 나노하이드록시아파타이트의 작용기전

Three functions of nano were recognized by Japanese health authorities in approving it as an active anticaries ingredient in 1993, namely :

① Adhesion to and Removal of Plaque 플라그의 흡착과 제거

<mHAP> has a strong propensity to bind with protein, and adheres to bacteria and plaque fragments during brushing, facilitating their removal on rinsing from the mouth. This feature is enhanced by <mHAP>’s nanoparticle size, which increases the surface area to which proteins attach.

<mHAP> nanoparticles bind to S. mutans bacteria
(Electron Micrograph)

② Filling of Microscopic Surface Fissures 현미경단위의 표면손상 수복

<mHAP> also acts as a filler, repairing minute pits and fissures in the enamel surface.This function, also enhanced by its nano size, results in smoother, glossier enamel, with fewer sites likely to harbor plaque and stains

Enamel surface roughness (left) before and (right) after treatment with nano toothpaste.
RA=average surface roughness (nm)
(Scanning Probe Micrograph(SPM), Sangi Central Research Laboratory)

③ Remineralization of Subsurface Demineralized Areas　(Incipient Caries) 초기우식의 재광화

<mHAP> nanoparticles supplement the supply of mineral from saliva, remineralizing subsurface demineralized areas of the enamel (‘white spot’ lesions or incipient caries), and restoring mineral density and translucency to enhance the whiteness of the teeth.

Subsurface demineralized area (left) before and (right) after treatment with Nano toothpaste
(Contact Microradiogram, Sangi Central Research Laboratory)

By helping to remove plaque, and restoring smoothness and mineral density to both surface and subsurface enamel, <mHAP> nanoparticles not only protect against decay, but restore translucency and gloss, contributing to both the health and natural beautyof the teeth.

Antihypersensitivity Dentinal Tubular Occlusion 지각과민증상의 완화: 상화세관의 봉쇄

Sangi's nanohydroxyapatite toothpaste, in both in vitro and in situ tests, has been shown to occlude exposed dentinal tubules and create a fine hydroxyapatite coating over the exposed dentinal surface. Preliminary clinical studies and consumer trials indicate that it is effective in alleviating dentinal hypersensitivity.

Exposed dentinal surface and tubules, (a) before and
(b) (c) after treatment with Sangi's nanohydroxyapatite toothpaste

Cross-section of (b), showing tubular occlusion and surface coating by Sangi's nano-hydroxyapatite

(K.Ohta et al. Occlusion of Dentinal Tubules by Nano-Hydroxyapatite)
(Amaechi et al, Evaluation of Nano-hydroxyapatite-containing Toothpaste for Occluding Dentin Tubules )

PROFESSIONAL BENEFITS 치과의사(치위생사)의 혜택

Mode of Action on the Teeth

<nHAP> nanoparticles

• fill and repair areas of minute surface abrasion
• remineralize subsurface demineralized areas (incipient caries and white spot-lesions)
• supplement or replace inadequate or depleted tooth mineral
• occlude exposed dentin and dentinal tubules

Sangi’s Nanohydroxyapatite helps Dentists

• restore mineral and surface smoothness
  after PMTC
• remove white spots and surface unevenness
  after debonding
• reduce sensitivity and return of discoloration
  after bleaching
• provide supplementary mineral
  for enamel dysplasia or children’s teeth
  
• protect against incipient caries, in particular root caries

Enamel Restoractive Functions Clinical use of <nHAP> 에나멜 수복기능: 나노하이드록시아파타이트의 임상적용

① After PMTC 전문가에 의한 스켈링과 치아세정후

fills surface fissures and restores smoothness to the enamel after scaling and use of polishing abrasives during professional mechanical tooth cleaning (PMTC)

② After Debonding 교정치료시 브라켓과 시멘트 제거후

remineralizes enamel roughened or demineralized during orthodontic procedures such as cementing or debonding (removal of orthodontic brackets), restoring smoothness and reducing white spots.

③ After Bleaching 치아미백후

<nHAP> replenishes mineral lost during bleaching, restoring enamel density and smoothness, and protecting against sensitivity and early recurrence of stains.

･Restoration of post-bleach enamel smoothness

･Protection against post-bleach stain recurrence

Teeth either treated (a) or not treated (b) with nano ＜mHAP＞ paste after bleaching were
immersed successively in red wine, then a stain remover (PEG), for three cycles.
(M.Nishio et al, Post-bleach Stain lnhibition by Nano-Hydroxyapatite:a Cyclical Staining Test)