Transcript Oligosaccharides in Japan

Oligosaccharides in Japan
Shigeharu Mori, Ph.D.
AMANO ENZYME Inc.
On 25th March 2009
At FIC in Shanghai, China
1
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
2
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
Maltotoriohydrolase
Streptomyces griseus
Bacillus subtilis
Microbacterium imperiale
α- Maltotetraose
Maltotetraohydrolase
Pseudomonas stutzeri
P. saccharophila, B. circulans
α- Maltopentaose
Maltopentaose-forming
amylase
B. licheniformis, B. subtilis
B. Cereus, Pseudomonas sp.
α- Maltohexaose
Maltohexaohydrolase
Klebsiella pneumoniae, B. subtilis
B. circulans F-2, G-6
Fructooligosaccharides
β-Fructofuranosidase
A. niger
Trehalose
MTSase
MTHase
Arthrobacter sp.
Sulfolobus sp.
CGTase
Alkalophilic Bacillus sp.
B. Clarkii 7364
α- Maltotriose
Cyclodextrin
Reference : T.Nakakuki.: J. Appl. Glycosci. , 52. 268 (2005)
3
World No.1 Speciality Enzyme Producer founded in 1899
Various kinds of oligosaccharides by raw material
Sucrose-related
e.g.
・Fructooligosaccharides
・Palatinose
・Lactosucrose
・Others
Lactose-related
e.g.
・Galactooligosaccharides
・Lactosucrose
・Others
Starch-related
e.g.
・Trehalose
・Maltooligosaccharides
・Isomaltooligosaccharides
・Cyclodextrins(CD), branched-CD
・Others
Others
e.g.
・Xylooligosaccharides
・Raffinose
・Others
4
World No.1 Speciality Enzyme Producer founded in 1899
Production method of
oligosaccharides from
Starch
Starch
α-Amylase
Liquefied Starch
Glucoamylase
Pullulanase
α-Amylase
Dextrin
Cyclodextrin
glucanotoransferase
(CGTase)
Cyclodextrin
Pullulanase
Maltosyl
cyclodextrin
α-Amylase
β-Amylase
Tansglucosidase
Isomaltooligosaccharides
Maltooligosaccharides
-forming Amylase
β-Amylase
Pullunanase
Maltooligosaccharides
Maltose
Glucose
α-Glucosidase
Nigerooligosaccharides
β-Glucosidase
Gentiooligosaccharides
Glucose isomerase
High fructose
corn syrup
MTSase
MTHase
Trehalose
5
World No.1 Speciality Enzyme Producer founded in 1899
Production method of oligosaccharides
from Sucrose, Galactose and Starch
α-Galacto-
Palatinose
oligosaccharides
α-Galactosidase
α-Glucosyltransferase
Glucose
+
Galactose
β-Galactosidase
Starch
Sucrose
CGTase
β-Fructofuranosidase
β-Fructofuranosidase
Lactosucrose
Lactose
β-Galactosidase
Coupling sugar
Fructo-oligosaccharides
β-Galacto-oligosaccharides
6
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
substances
 Improvement of serum lipids
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)
7
World No.1 Speciality Enzyme Producer founded in 1899
Presumed production level in Japan
Oligosaccharides
tons / year
Major production/sales by
30,000
Hayashibara
Maltooligosaccharides
15,000
Sanwa Cornstarch, Kato kagaku
Nihon Shokuhin Kako, Nihon Corn
Starch, Showa Sangyo, et al
Isomaltooligosaccharides
15,000
Showa Sangyo, Nihon Shokuhin Kako,
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
Trehalose
Gentiooligosaccharides
500 – 1,000
Nihon Shokuhin Kako
Nigerooligosaccharides
500 – 1,000
Nihon Shokuhin Kako
Others (e.g. Xylooligo…)
1,000 – 2,000
Suntory
Reference : T.Nakakuki.: J. Appl. Glycosci. , 52. 268 (2005)
8
World No.1 Speciality Enzyme Producer founded in 1899
Oligosaccharide products in Japan
Manufacturing
Mothod
Company
Fructooligosaccharide
Enzymatic
conversion
Meiji Food Materia
(1-Kestose)
Galactooligosaccharide
Enzymatic
conversion
Yakult
Pharmaceutical
Industry
Nissin Sugar
Manufacturing
Ensuiko Sugar
Refining
Lactosucrose
Enzymatic
conversion
Hayashibara
Commercial
name
Form
Content
(%)
Price
(Yen/kg)
Meioligo G
Meioligo P
Meioligo P
Meioligo CR
Oligomate 55N
Oligomate 55NP
Syrup
Syrup
Powder
Crystal
Syrup
Powder
55
95
95
98
55
55
390
1,100
1,800
2,500
555
1,400
Cup-oligo H70
Cup-oligo P
Nyukaoligo LS-40L
Nyukaoligo LS-55L
Nyukaoligo LS-55P
Nyukaoligo LS-90P
Nyukaoligo 700
Syrup
Powder
Syrup
Syrup
Powder
Powder
Syrup
70
70
40
55
55
88
70
730
1,590
500
800
1,050
2,900
600
*)Ref.: Shokuhin to kaihatu, 42(12)
9
World No.1 Speciality Enzyme Producer founded in 1899
Oligosaccharide products in Japan (2)
Manufacturing
Mothod
Company
Xylooligosaccharide
Enzymatic
hydrolysis
Suntory
Isomaltooligosaccharide
Enzymatic
conversion
Showa Sangyo
Raffinose
Lactulose
Separation /
Purification
Isomerization
Nigerooligosaccharide
Gentiooligosaccharide
Enzymatic
conversion
Enzymatic
conversion
Nippon Beet Sugar
Manufacturing
Morinaga Milk
Industry
Nihon shokuhin kako
Nihon shokuhin kako
Commercial
name
Form
Content
(%)
Price
(Yen/kg)
Taste-oligo
Syrup
Powder
Powder
Syrup
Syrup
Powder
Crystal
Powder
Syrup
Powder
Syrup
70
95
35
50
85
85
98
98
50
97
40
2,500
7,000
2,700
150
350
500
2,000
2,000
1,000
5,000
350
Gentose
Syrup
45
350
Xylooligo 70
Xylooligo 95P
Xylooligo 35P
Isomalto 500
Isomalto 900
Isomalto 900P
Nitten Raffinose
Nitten Raffinose FP
Milk-oligo
*)Ref.: Shokuhin to kaihatu, 42(12)
10
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
11
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
FOSHU
FOSHU
847 items
(March 2009)
Food with Nutrient
Function Claims
Other Food
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
Seal for FOSHU approval
Requirements 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
13
World No.1 Speciality Enzyme Producer founded in 1899
Oligosaccharides in FOSHU
Specified Health Uses
Principal Ingredients (ingredients exhibiting
health functions)
Foods to modify gastrointestinal conditions
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.)
Foods related to blood cholesterol level
Chitosan, soybean protein, degraded sodium alginate
Foods related to blood sugar levels
Indigestible dextrin, wheat albumin, guava tea polyphenol, Larabiose, etc.
Foods related to blood pressure
Lactotripeptide, casein dodecaneptide, tochu leaf glycoside
(geniposidic acid), sardine peptide, etc.
Foods related to dental hygiene
Palatinose, maltitiose, erythrytol, etc.
Cholesterol plus gastrointestinal conditions, Degraded sodium alginate, dietary fiber from psyllium seed husk,
etc.
triacylglycerol plus cholesterol
Foods related to mineral absorption
Calcium citrated malate, casein phosphopeptide, hem iron,
Fructooligosaccharide, etc.
Foods related to osteogenesis
Soybeen isoflavone, MBP (Milk basic protein), etc.
Foods related to triacylglycerol
Middle chain fatty acid, etc.
14
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
15
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
(Effectiveness)
効果確認
Consultation
(Safety)
安全性確認
Council on Pharmaceutical and
Food Sanitation
（薬事・食品衛生審議会）
Food Safety
Commission
（食品安全委員会）
16
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
内容量：130g,300g
製造あるいは販売者：塩水港精糖株式会社
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
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
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）
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。
関与成分についての解説： 【関与成分および作用機序】
【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】
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
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
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
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
【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。
【関与成分の構造式】
安全性に関する評価
・Product : “Oligo no okage” (Thanks Oligo)
・Shape : Table sugar
・Manufacturer : Ensuiko Sugar Co.
・Approved claim on label :Food which
contains lactosucrose as main
component and contributes in keeping
good stomach condition with proper
growth of bifidobacterium in intestine.
・Approved date : Oct 23, 1997
・Appropriate intake : 8 – 20g (2-5 spoonful,
2.4 – 6.0g as lactosucrose ) a day
・Notification : may cause upset stomach in
case of excess intake and/or dependent
on a certain body condition
・(Other subjects) :
Description of component involved :
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
property & functions
Government support for
claim assurance
Production technology
including enzymes
18
World No.1 Speciality Enzyme Producer founded in 1899
Locations
Amano Enzyme
Before closing …let us introduce our company
Europe
Amano Enzyme
Amano Enzyme
Japan
USA
Shizuoka
Amano Enzyme
China
Daiwa
Amano Enzyme
Mexico
AMANO ENZYME Company
19
16
World No.1 Speciality Enzyme Producer founded in 1899
Thanks all,
20
World No.1 Speciality Enzyme Producer founded in 1899