Oligosaccharides in Japan

Shigeharu Mori, Ph.D.

AMANO ENZYME Inc.
On 25th March 2009
At FIC in Shanghai, China

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World No.1 Speciality Enzyme Producer founded in 1899
 Purpose : Introduction of oligosaccharides
and their applications in Japan
Contents :
• Development of oligosaccharides in Japan
• Various kinds of oligosaccharides by raw materials
• Production method of oligosaccharides by using the enzymes
• Functions of oligosaccharides
• Presumed production level of oligosaccharides in Japan
• Example of commercial products with oligosaccharides
• FOSHU (特定保健用食品) in Japan
• Summary

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World No.1 Speciality Enzyme Producer founded in 1899
 Development of oligosaccharides in Japan
Since 1970 several novel microbial enzymes were discovered,
and the characters of oligosaccharides were studied.

Product Enzyme Microbial origin

α- Maltotriose Maltotoriohydrolase
α- Maltotetraose Maltotetraohydrolase
Maltopentaose-forming
α- Maltopentaose amylase
Klebsiella pneumoniae, B. subtilis
α- Maltohexaose Maltohexaohydrolase
Streptomyces griseus
Bacillus subtilis
Microbacterium imperiale
Pseudomonas stutzeri
P. saccharophila, B. circulans
B. licheniformis, B. subtilis
B. Cereus, Pseudomonas sp.
B. circulans F-2, G-6

Fructooligosaccharides β-Fructofuranosidase A. niger

MTSase Arthrobacter sp.
Trehalose MTHase Sulfolobus sp.

Alkalophilic Bacillus sp.

Cyclodextrin CGTase B. Clarkii 7364

Reference : T.Nakakuki.: J. Appl. Glycosci. , 52. 268 (2005)

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World No.1 Speciality Enzyme Producer founded in 1899
Various kinds of oligosaccharides by raw material

Sucrose-related Starch-related
e.g.
e.g. ・Trehalose
・Fructooligosaccharides ・Maltooligosaccharides
・Palatinose ・Isomaltooligosaccharides
・Lactosucrose ・Cyclodextrins(CD), branched-CD
・Others ・Others
Lactose-related Others

e.g. e.g.
・Galactooligosaccharides ・Xylooligosaccharides
・Lactosucrose ・Raffinose
・Others ・Others
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World No.1 Speciality Enzyme Producer founded in 1899
Production method of α-Amylase Dextrin
oligosaccharides from
Cyclodextrin
Starch glucanotoransferase Cyclodextrin
(CGTase)
Starch Maltosyl
Pullulanase cyclodextrin
α-Amylase α-Amylase
β-Amylase Isomalto-
Tansglucosidase oligosaccharides
Liquefied Starch
Maltooligosaccharides
Malto-
-forming Amylase
Glucoamylase oligosaccharides
Pullulanase β-Amylase
Pullulanase Maltose
Glucose
Nigero-
α-Glucosidase
Glucose isomerase
oligosaccharides

β-Glucosidase Gentio-
High fructose oligosaccharides
corn syrup
MTSase
MTHase Trehalose 5
World No.1 Speciality Enzyme Producer founded in 1899
 Production method of oligosaccharides
from Sucrose, Galactose and Starch

Palatinose α-Galacto- Glucose

oligosaccharides
+
α-Glucosyltransferase α-Galactosidase Galactose

β-Galactosidase

Starch Sucrose β-Fructofuranosidase Lactose

CGTase β-Fructofuranosidase
Lactosucrose
β-Galactosidase
Coupling sugar
Fructo-oligosaccharides β-Galacto-oligosaccharides

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World No.1 Speciality Enzyme Producer founded in 1899
Functional properties of oligosaccharides
・Physiochemical property ・Biological property
✓ Taste (sweetness / bitterness) ✓ Digestibility / Non-digestibility
✓ Bulkiness ✓ Non-cariogenicity / Anti- cariogenicity
✓ Hygroscopicity ✓ Bacteriostatic action
✓ Water activity ✓Selective proliferation of bifidobacteria
✓ Stabilization of active ✓ Improvement of serum lipids
substances and blood glucose
✓ Inclusion capacity ✓ Effects on adsorption of minerals,
etc.

Other property : Substrate for enzyme, Enzyme inhibitor, etc.

Reference : T.Nakakuki.: J. Appl. Glycosci. , 52. 268 (2005)
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World No.1 Speciality Enzyme Producer founded in 1899
 Presumed production level in Japan
Oligosaccharides tons / year Major production/sales by
Trehalose 30,000 Hayashibara
Sanwa Cornstarch, Kato kagaku
Maltooligosaccharides 15,000 Nihon Shokuhin Kako, Nihon Corn
Starch, Showa Sangyo, et al
Showa Sangyo, Nihon Shokuhin Kako,
Isomaltooligosaccharides 15,000 Nihon Corn Starch
Galactooligosaccharides 6,500 Yakult, Nisshin Sugar
Palatinose 5,000 Mitsui Sugar
Cyclodextrin, branched CD 4,000 Ensuiko, Nihon Shokuhin Kako
Fructooligosaccharides 3,500 Meiji
Lactosucrose 2,500 Ensuiko
Glycosylsucrose 2,000 Hayashibara
Gentiooligosaccharides 500 – 1,000 Nihon Shokuhin Kako
Nigerooligosaccharides 500 – 1,000 Nihon Shokuhin Kako
Others (e.g. Xylooligo…) 1,000 – 2,000 Suntory
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Reference : T.Nakakuki.: J. Appl. Glycosci. , 52. 268 (2005)
World No.1 Speciality Enzyme Producer founded in 1899
 Oligosaccharide products in Japan
Manufacturing Commercial Content Price
Company Form
Mothod name (%) (Yen/kg)
Fructo- Enzymatic Meiji Food Materia Meioligo G Syrup 55 390
oligosaccharide conversion Meioligo P Syrup 95 1,100
Meioligo P Powder 95 1,800
(1-Kestose) Meioligo CR Crystal 98 2,500
Galacto- Enzymatic Yakult Oligomate 55N Syrup 55 555
oligosaccharide conversion Pharmaceutical Oligomate 55NP Powder 55 1,400
Industry
Nissin Sugar Cup-oligo H70 Syrup 70 730
Manufacturing Cup-oligo P Powder 70 1,590
Lactosucrose Enzymatic Ensuiko Sugar Nyukaoligo LS-40L Syrup 40 500
conversion Refining Nyukaoligo LS-55L Syrup 55 800
Nyukaoligo LS-55P Powder 55 1,050
Nyukaoligo LS-90P Powder 88 2,900
Hayashibara Nyukaoligo 700 Syrup 70 600

*)Ref.: Shokuhin to kaihatu, 42(12)

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World No.1 Speciality Enzyme Producer founded in 1899
 Oligosaccharide products in Japan (2)
Manufacturing Commercial Content Price
Company Form
Mothod name (%) (Yen/kg)
Xylo- Enzymatic Suntory Xylooligo 70 Syrup 70 2,500
oligosaccharide hydrolysis Xylooligo 95P Powder 95 7,000
Xylooligo 35P Powder 35 2,700
Isomalto- Enzymatic Showa Sangyo Isomalto 500 Syrup 50 150
oligosaccharide conversion Isomalto 900 Syrup 85 350
Isomalto 900P Powder 85 500
Raffinose Separation / Nippon Beet Sugar Nitten Raffinose Crystal 98 2,000
Purification Manufacturing Nitten Raffinose FP Powder 98 2,000
Lactulose Isomerization Morinaga Milk Milk-oligo Syrup 50 1,000
Industry Powder 97 5,000
Nigero- Enzymatic Nihon shokuhin kako Taste-oligo Syrup 40 350
oligosaccharide conversion
Gentio- Enzymatic Nihon shokuhin kako Gentose Syrup 45 350
oligosaccharide conversion

*)Ref.: Shokuhin to kaihatu, 42(12)

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World No.1 Speciality Enzyme Producer founded in 1899
 Commercial products with
oligosaccharides in the market of Japan

Example No.2
Example No.3
Example No.1
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World No.1 Speciality Enzyme Producer founded in 1899
 FOSHU (Food for Specified Health Use)
特定保健用食品 FOOD
Seal for FOSHU
approval
DRUG

Food with Nutrient Other Food

FOSHU Function Claims

FOSHU
847 items
(March 2009) Food with Health Claims

・FOSHU refers to foods containing ingredient with functions for health and officially
approved to claim its physiological effects on the human body. FOSHU is intended
to be consumed for the maintenance / promotion of health or special health uses by
people who wish to control health conditions, including blood pressure or blood
cholesterol. In order to sell a food as FOSHU, the assessment for the safety of the
food and effectiveness of the functions for health is required, and the claim must be
approved by the MHLW. On 1991, the system of FOSHU set up in Japan.
・FOSHU can bear the seal of FOSHU approval on the label of the product. 12
World No.1 Speciality Enzyme Producer founded in 1899
FOSHU (Food for Specified Health Use)
特定保健用食品
Requirements for FOSHU Approval Seal for FOSHU approval

• Effectiveness on the human body is clearly proven

• Absence of any safety issues (animal toxicity tests,
confirmation of effects in the cases of excess intake, etc.)
• Use of nutritionally appropriate ingredients (e.g. no
excessive use of salt, etc.)
• Guarantee of compatibility with product specifications by the
time of consumption
• Established quality control methods, such as specifications
of products and ingredients, processes, and methods of
analysis

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World No.1 Speciality Enzyme Producer founded in 1899
 Oligosaccharides in FOSHU
Specified Health Uses
Foods to modify gastrointestinal conditions
Foods related to blood cholesterol level
Foods related to blood sugar levels
Foods related to blood pressure
Foods related to dental hygiene
Cholesterol plus gastrointestinal conditions, Degraded sodium alginate, dietary fiber from psyllium seed husk,
triacylglycerol plus cholesterol
Foods related to mineral absorption
Foods related to osteogenesis
Foods related to triacylglycerol
Principal Ingredients (ingredients exhibiting
health functions)
Oligosaccharides (Isomalto-, Galacto-,Xylo-, Fruct-, Soy bean,
Lactosucrose, Lactulose), lactose, bifidobacteria, lactic acid
bacteria, dietary fiber 8 ingestible dextrin, polydextrol, guar gum,
psyllium seed coat, etc.)
Chitosan, soybean protein, degraded sodium alginate
Indigestible dextrin, wheat albumin, guava tea polyphenol, L-
arabiose, etc.
Lactotripeptide, casein dodecaneptide, tochu leaf glycoside
(geniposidic acid), sardine peptide, etc.
Palatinose, maltitiose, erythrytol, etc.
etc.
Calcium citrated malate, casein phosphopeptide, hem iron,
Fructooligosaccharide, etc.
Soybeen isoflavone, MBP (Milk basic protein), etc.
Middle chain fatty acid, etc.
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World No.1 Speciality Enzyme Producer founded in 1899
 Application for Registration (登録申請)
of FOSHU product
Procedure of application for registration of FOSHU
特定保健用食品の申請手続
（１）Submission of dossier for investigation and approval
許可申請書及び審査申請書の提出
[1] 許可申請書を主たる営業所の所在地の保健所に提出する。 （提
出部数：正本１部、副本２部）
[2] 許可申請書の提出を受けた都道府県知事等は、許可申請書の不
備の有無を点検の上、適当と認められるものを厚生労働大臣に
進達する。
[3] 許可等申請書の提出を行った後、許可申請書の写しを添付して、
審査申請書（添付資料を含む。以下同じ。）を、厚生労働省医薬
食品局食品安全部基準審査課新開発食品保健対策室に直接送
付又は持参する。
（提出部数：正本１部、副本１部）
※ 承認申請の場合は、承認申請書及び審査申請書を直接厚生労働
省に提出する。

（２）Request for testing the product sample

製品見本の試験検査依頼
[1] 申請者は、製品見本に審査等申請書の写しを添付して、独立行政
法人国立健康・栄養研究所（以下「研究所」という。）又は登録試
験機関に試験検査を依頼する。
[2] 申請者は、研究所又は登録試験機関が発行した検査成績書の原
本を新開発食品保健対策室長に提出する。
※ 申請手続きの詳細及び申請書の様式については、平成１７年２月
１日付け食安発第０２０１００２号を参照
～ 申請手続きに関するご相談はお近くの保健所へ ～ 保健所一覧へ
※ 特定保健用食品（規格基準型）については、（ ）部分を省略

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World No.1 Speciality Enzyme Producer founded in 1899
 Flow chart of FOSHU approval
Applicant （申請者）
Submission (申請) Approval (許可)

Ministry of Health, Labor, and Welfare

（厚生労働省）
Consultation Consultation
(Effectiveness) (Safety)
効果確認 安全性確認
Council on Pharmaceutical and Food Safety
Food Sanitation Commission
（薬事・食品衛生審議会） （食品安全委員会）
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World No.1 Speciality Enzyme Producer founded in 1899
 Example of FOSHU（特定保健用食品）：
“Oligo no okage” 「オリゴのおかげ」 (Thanks Oligo)
商 品 詳 細 ： 食品名 「オリゴのおかげ」
形態：テーブルシュガ
・Product : “Oligo no okage” (Thanks Oligo)
内容量：130g,300g
製造あるいは販売者：塩水港精糖株式会社
・Shape : Table sugar
住所：東京都中央区日本橋堀留町2-9-6 電話番号：（代）
03(3249)2381
許可された実際の表示：乳果オリゴ糖を主成分とし、腸内のビフィズ
・Manufacturer : Ensuiko Sugar Co.
ス菌を適正に増やして、おなかの調子を良好に保つ食品です。
許可された年月：平成9年10月23日 ・Approved claim on label :Food which
適切な利用法： 8～20g（ティースプーン2～5杯程度；関与成分「乳果
オリゴ糖」として、2.4g～6.0g） contains lactosucrose as main
利用上の注意事項：食べ過ぎあるいは体質・体調によりおなかがゆ
るくなることがあります。 component and contributes in keeping
関与成分についての解説： 【関与成分および作用機序】 good stomach condition with proper
【関与成分の特性】関与成分である乳果オリゴ糖は、腸内有用菌の代表であ
るビフィズス菌によって選択的に代謝される。
【作用・効果および機序】
growth of bifidobacterium in intestine.
大腸に棲息する腸内細菌には、ヒトの健康維持に有効な役割を果たす有用菌
と、腐敗産物や発癌性物質を作ったり、下痢や便秘など疾病を引き起
こす原因となる有害菌が存在し、これらが腸内でバランスを保って菌叢
・Approved date : Oct 23, 1997
・Appropriate intake : 8 – 20g (2-5 spoonful,
を形成している。従って有用菌優勢の菌叢を保つことが健康を維持す
るうえで重要となってくる。乳果オリゴ糖は、腸内細菌によって代謝され
有機酸を生成する。有機酸は、腸の蠕動運動や腸管からの水の分泌
を促進するとともに、腸管内を酸性に保ち、その結果腐敗産物の生産
抑制、便性・便通の改善効果をもたらす。腸内細菌の中でもビフィズス
菌はその作用が顕著である。この他にもビフィズス菌は、ビタミンB群を
2.4 – 6.0g as lactosucrose ) a day
作ったり、病原菌の侵入を防いだり、有害菌の繁殖を抑えたり、免疫力
を高める作用がある。また、乳果オリゴ糖は、有用菌であるビフィズス ・Notification : may cause upset stomach in
case of excess intake and/or dependent
菌や一部の乳酸菌に選択的に代謝され、悪玉菌のClostridiumや
Escherichia Coliには代謝され難いことが示されている。
出典：
日本食品新素材研究会誌、3(2), I 66-72 on a certain body condition
【関与成分の分析方法】
試験溶液を順相系カラムを用いるHPLCによりクロマトグラムを得て、検量線よりその
ピーク高さ又は面積と量比から乳果オリゴ糖を定量する。 ・(Other subjects) :
【関与成分の構造式】
Description of component involved :
安全性に関する評価 analytical method, structure, mode of
function, safety data, etc. 17
World No.1 Speciality Enzyme Producer founded in 1899
 Summary
Development of food
using Oligosaccharides

Research of Government support for

property & functions claim assurance

Production technology
including enzymes
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World No.1 Speciality Enzyme Producer founded in 1899
Locations Before closing …let us introduce our company

Amano Enzyme Europe

Amano Enzyme Japan
Amano Enzyme USA

Shizuoka

Amano Enzyme China

Daiwa
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AMANO ENZYME Company

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World No.1 Speciality Enzyme Producer founded in 1899
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Thanks all,

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World No.1 Speciality Enzyme Producer founded in 1899