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실험실Originality, with a Flexible ApproachThe primary emphasis in Sangi’s research is originality – to conceive and pursue new ideas and obtain its own patents, with the aim of moving beyond conventional wisdom in creating new, previously unavailable products and technologies and developing new markets for them.
As a result, Sangi aims for optimum flexibility at its Central Research Laboratory in Kasukabe, just north of Tokyo. Leveraging its strengths, research is carried out not just in-house, but wherever possible in active cooperation with outside research facilities, both corporate and academic, in a variety of fields. This includes funding of projects and scholarships for outside research. Another factor favoring this flexibility is the fact that Sangi, by design, has no manufacturing facilities, but carries out all products development to the pilot plant stage.
치과 제품들Continuing Innovation, based on Hydroxyapatite1) Development of Toothpaste and Other Personal Care Products The main thrust of Sangi’s toothpaste research is to develop new formulations and technologies that will further enhance the existing benefits of nano Medical Hydroxyapatite (nano ‹mHAP›).
One approach is to study the remineralization enhancement effect, in combination with nano‹mHAP›, of candidate substances derived from fields such as foodstuffs, cosmetics and pharmaceuticals. Another is to develop new formulations. Even using the same substance, combination with materials having different properties, or adjustment of composition volumes can lead to different stimulatory effects on the action of the remineralizing ingredient. The aim is to offer consumers ever-better products under our own brand, and our OEM customers products with characteristics that are best suited to them.
We are also constantly working on improving nano‹mHAP› itself. Different methods of synthesis make it possible to modify the ingredient’s particle morphology and adsorption characteristics, both to improve its existing effects and to discover previously unknown properties. The aim of these tests is to go beyond nano‹mHAP›’s existing anticaries and whitening effects, based on remineralization, to demonstrate its additional and potential benefits in alleviating oral and systemic diseases beyond those of the teeth, such as periodontal disease, now linked to diseases throughout the body, aspiration pneumonia in the elderly, and the easing of hyperesthesia.
Sangi is also going beyond oral care, to develop personal care products in the cosmetics field, such as facial washes and cleansers, drawing on properties of hydroxyapatite such as its ability to efficiently adsorb and remove flaking cells and oils from the surface of the skin. 2) Development of Products for Professional Use Sangi has also put the properties of hydroxyapatite to use in working to develop dental materials and medical equipment for dental professional use. Most of these are firsts in the field, and the accumulation of data from laboratory experiments and clinical trials necessary for regulatory approval requires considerable time. Two examples are introduced here. ① Bacterial Removal System (BRS) The goal of this system, using the bacterial adsorption properties of fine particle hydroxyapatite, is to reduce the proportion, within the total oral bacterial flora, of mutans streptococci, one of the key pathogens implicated in tooth decay – aiming to create a healthier oral environment less susceptible to the development of caries.
To achieve this goal, a new type of hydroxyapatite with enhanced adsorption properties for the target bacteria was developed, and applied to the teeth as a cream in a dental retainer tray immediately after professional mechanical tooth cleaning (PMTC) and then once daily for a week thereafter. Clinical trials in Japan showed the proportion of the target bacteria fell after just one week’s treatment, and remained low for the next two months, and subsequent clinical tests also suggested two months as an appropriate recall period.
The prototype product showed no evidence of allergic reactions or bacterial resistance arising, as can be seen with sterilizing systems involving antibacterial agents, and was considered safe to use. Work on its development is still continuing. ②Powder Jet Deposition System (PJD)  Developed in conjunction with Japan’s Tohoku University, this system, in which ultra-fine hydroxyapatite particles are blasted at high speed onto the surface of the tooth, represents a revolutionary approach to future dental care.
By directly creating a new layer of enamel on the tooth surface, virtually indistinguishable from the existing substance of the tooth (since tooth enamel naturally comprises 97% hydroxyapatite), it opens the way to future clinical applications including cavity sealing during traditional drill-and-fill cavity repair, occlusion and coating of exposed dentinal tubules, to prevent hypersensitivity, whitening of discolored teeth, by providing a new surface layer rather than by abrasion or bleaching as in traditional methods, and protection against caries of susceptible teeth, for example in children, by providing and additional layer of hydroxyapatite on the surface of the teeth.
Consisting of a specially designed spray unit and handpiece, and specifically designed hydroxyapatite powders, the PJD system has been shown to be safe and effective in preliminary clinical trials, and has been the object of successive government grants from the Japan Science and Technology Agency (JST). The next step to complete is a full-scale, possibly multi-centered clinical trial. 
DRUG DELIVERY (DDS)Targeting Oral Administration of Poorly Soluble Drugs
Cross-section a image showing a hydroxyapatite-coated drug
Due to its strong biocompatibility in the human body, hydroxyapatite has been studied widely in drug delivery applications, chiefly to improve dose efficiency by lesion targeting and slow release of the drug, once it reaches the target site. Sangi’s drug delivery research, in contrast, is aimed at improving the solubility and internal absorption of drugs that are poorly soluble and/or poorly absorbed, allowing them to be administered orally (for example in tablets) instead of by injection or intravenous infusion, for which hospitalization or a hospital visit is usually required. This is especially important in the case of cancer drugs to improve patient quality of life.
To achieve this, Sangi has developed a proprietary technology for coating drugs with hydroxyapatite that can not only improve solubility and absorption of the drug, but also reduce both the volume required and the level of side effects. Sangi’s formulation technology principally targets drugs in Class II of the U.S. Biopharmaceuticals Classification System (BCS) which show high levels of membrane permeability but low solubility, and those in Class IV which show both low membrane permeability and low solubility. 
Example showing bezafibrate (BCS Class II), a poorly soluble drug. The drug alone fails to dissolve in water (A), but when coated with hydroxyapatite it immediately dissolves (B). INDUSTRIAL CATALYSTSHydroxyapatites as CatalystsHydroxyapatite, a calcium phosphate compound, has the unique characteristic that its chemical composition can be altered without destroying its fundamental crystalline structure. Other elements can be substituted for some of its calcium or phosphate and some components may even be left out, allowing significant scope for variation in its physicochemical attributes.
Because of this unique tolerance for fine tuning of its component elements and its ability to endure significant distortions of its crystal lattice while still maintaining its basic structure, hydroxyapatite offers a wide range of possibilities as a catalyst for use in chemical engineering applications, through adjustments to its morphological configuration and its calcium to phosphorous ion ratio that can be made according to the method of synthesis.
By developing technology to control hydroxyapatite’s various characteristics, Sangi has successfully achieved catalyzing functions that are not present in other catalysts. This technology has progressed from beaker scale to industrial scale, making it possible to manufacture the catalysts at an industrial level. Synthesis of Industrial Chemicals from Biomass-derived Raw MaterialsSangi’s research into catalysts began in the 1990s with the synthesis of bio-gasoline, a chemical mixture very close to high-octane fuel, obtained using plant-derived ethanol as raw material. This research was then taken further to focus on synthesis of a number of valuable chemical products from bio-ethanol and other biomass-derived raw materials.
Apatite catalysts, with their finely controlled properties, possess a variety of catalyzing functions not found in existing solid catalysts. For example, they make it possible to selectively synthesize higher alcohols from ethanol, with selectivity of over 70% in the case of n-butanol, a product vitally important in the chemical industry as a material for paint solvents and plasticizing agents, and superior in chemical properties to ethanol as a replacement for gasoline. Sangi’s technology makes it possible to manufacture, from environmentally friendly, biomass-derived ethanol, a range of industrial chemicals that are still commercially fossil fuel derived.
In addition, Sangi is working collaboratively with university researchers to selectively synthesize acrylic acid from lactic acid using hydroxyapatite catalysts. Since lactic acid is currently produced from biomass-derived materials, this raises the prospect of acrylic acid, a key raw material for the production of super-absorbent polymers and a wide range of products, being synthesized in future from an environmentally friendly source.
The reaction synthesizing n-butanol from ethanol using a hydroxyapatite catalyst
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