JP4242293B2 - 骨の強化および骨形成を増加させるための組成物 - Google Patents
骨の強化および骨形成を増加させるための組成物 Download PDFInfo
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- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
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- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
- A23C9/1307—Milk products or derivatives; Fruit or vegetable juices; Sugars, sugar alcohols, sweeteners; Oligosaccharides; Organic acids or salts thereof or acidifying agents; Flavours, dyes or pigments; Inert or aerosol gases; Carbonation methods
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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Description
本発明の目的は、ミネラルのアベイラビリティを高め、 ミネラルのアベイラビリティに関連する障害、疾患、損傷を予防、軽減、治療し得る産物を利用可能にすることである。産物の、カルシウム吸収、破骨細胞形成の低下、造骨細胞形成の発達、健康な骨格系、および骨粗しょう症およびその前段階の予防および軽減に対する作用が特に重要である。
図1は、ラットの骨密度に対する本発明により使用される産物の作用および種々の参照サンプルの作用を示す。
本発明によって、ミネラルのアベイラビリティを高めるペプチドまたはそれを含有する産物を用いて上記の目的を達成できることがわかった。 ジ-、トリ-、テトラペプチドおよびそれらの混合物が、とりわけミネラルのアベイラビリティを高めるペプチドである。これらのペプチドは、カゼインまたはカゼイン含有の出発材料から発酵により都合よく調製できる。特に好ましいのは、生物学的活性ペプチドを含有する産物を発酵によりつくり、ついで濃縮し、そして組成物をナノろ過により完成する方法である。好ましい実施態様は、詳しく下記するように、異なる型の出発材料を使用し、所望のように最終産物の組成を改変する優れた可能性を提供する。
種々の産物のタンパク質分解度およびミネラル含量
種々のサワーミルク産物のタンパク質分解度を決定するために、そのタンパク質含量(タンパク質)、全窒素含量 (Tot.N)、非タンパク質窒素含量(NPN; 尿素、アミノ酸、小さいペプチドなど)、滴定された遊離アミノ酸の量(Titr.f.aa)、pH を測定した。タンパク質分解度は、非タンパク質窒素の全窒素に対する比率(NPN / Tot.N)を計算しておおまかに決め得る; 滴定の遊離アミノ酸 mmol/g タンパク質の量は Titr.aa/Prot を計算して得ることができる。
種々の産物の骨格系に対する作用
水、ミルク、サワーミルク、および2種の IPP および VPP ペプチド含有飲料、日本のカルピル食品工業株式会社の市販カルピス、サワーミルク産物および実施例2の産物 X (Evolus, Valio Oy) の骨格系に対する作用を調べた。
IPP、VPP および L. helveticus で形成されたペプチドフラクションの骨細胞形成に対する作用
本試験の目的は参考例2で得られた結果の原因となる活性因子を決定することである。試験において、L. helveticus を用いて乳酸発酵されたミルク産物のペプチドフラクション、Neo サワーミルク(Valio Oy, Helsinki, Finland) のフラクション、および L. helveticus で形成された純粋のペプチド、IPP (イソロイシン-プロリン-プロリン) および VPP (バリン-プロリン-プロリン) を骨形成細胞に加えた。骨形成を試験中に蓄積されたカルシウム量で測定した。ベースライン群で放出されたカルシウムの平均量を値 100% とした。ベースライン(BL、負対照) および骨形成を増加する物質である BMP-4 (C, 骨形態形成タンパク質 4) を試験での対照に使用した。骨形成における VPP および IPP の作用を図3および4に示す。異なる VPP および IPP 含量(-10、-8、-6、-4 = 10 -10 、10 -8 、10 -6 、10 -4 M VPP または IPP ペプチド)を用いてそれぞれ形成されたカルシウム含量である。 * (p < 0.05)、** (p < 0.01)、*** (p < 0.001) はベースラインからの統計的有意差を表す。
L helveticus で乳酸発酵されたミルク産物のカルシウム吸収に対する作用
本試験で、L. helveticus を用いて乳酸発酵されたミルク産物(Evolus) および Neo サワーミルク(Valio Oy, Helsinki, Finland)の閉経期後の女性における間接的カルシウム吸収に対する作用を調べた。20人が試験に参加し、別個の日に両産物を摂取した。この産物は 500 mg のカルシウムを含む。血液および尿のサンプルを試験日に採取した。カルシウムの吸収の測定を間接的に、主要な変数として血清中の副甲状腺ホルモン(PTH)および尿中のカルシウム(この量はカルシウム吸収中にすでに数時間で変化した)、および血清中の全カルシウム (S-Ca)およびイオン化カルシウム (iCa)を用いて行った。PTH で血液循環における十分なカルシウム含量を確認した。カルシウムの吸収が増加すればするほど、PTH が減少する。カルシウムの吸収は尿および血清におけるカルシウムを増加する。
結果は、カルシウム吸収が L. helveticus を用いて乳酸発酵されたミルク産物で通常の乳酸発酵法で調製された Neo サワーミルクよりもよいことを明白に示す。
Lactobacillus helveticus 株 LBK 16-H を MRS ブロスで 37 ℃、24 時間生育し、再構築ミルク(10%) に接種して、接種物をつくった。2生育サイクル後、接種物 (15%) を、9 〜 10% スクムミルク粉末でつくられ、110 ℃で 10 分間殺菌された発酵培地に接種した。発酵を、37 ℃で 22 〜 24 時間連続的に強く攪拌して行った。産物は乾燥および/または粉砕形態で使用でき、または所望のペプチドを方法自体既知の方法で分離できる。
実施例1で乳酸発酵された産物を下記のようにナノろ過した。
サワーミルクの pH を約 4.6 まで KOH で上げて、カゼインを diamond メッシュで除去した。残りのカゼインダストを遠心分離で除去した。GLL Conc. ラクターゼ (Biocon Ltd, Japan) をホエーに加え、5 ℃で 24 時間加水分解し、ラクトースをモノサッカライドに分解した。前処理されたホエーを Nanomax-50 膜 (Millipore)でナノろ過した。
実施例1に記載の発酵を、(a) 濃厚ミルクおよび (b) バターミルクをスキムミルクの代わりに用いて反復した。
Lactobacillus helveticus 株 LBK 16-H を MRS ブロスで 37 ℃、24 時間生育し、実施例1のように、接種物をつくった。再構築ミルク(10%) に接種して、接種物 (15%) を、酸沈降カゼイン (2.8%) およびグルコース (2.5%) の水溶液でつくられた発酵培地に接種した。pH を 6.7 に 10% KOH で上げてカゼインを溶解した。発酵を 37 ℃、22 〜 24 時間で行った。対応量の生物学的活性ペプチド VPP および IPP が、ミルクの発酵とともに産物中にできたが、カゼインからペプチドの分離はミルクからよりも容易であった。
ミネラルの吸収を高めるペプチドを含有するサワーミルクを、実施例1で得られたペプチドの 3.5% 濃縮物を市販のサワーミルクに加えて調製した。得られた産物の組成を表6に示す。表6は、第2の市販サワーミルク産物、AB サワーミルク、Valio Oy の組成との比較も示す。
Claims (6)
- 骨の強化および骨形成を増加させるための、Ile-Pro-Pro および/または Val-Pro-Proを含む組成物。
- 乳酸菌によるカゼイン含有出発材料の発酵により得られる産物を含む、請求項1記載の組成物。
- 乳酸菌がLactobacillus helveticus 株 LBK-16H、DSM 13137 である、請求項2記載の組成物。
- カゼイン含有出発材料の発酵により得られる発酵産物から、選択的にカゼインおよび/または他のミルクタンパク質および/またはラクトースを部分的にまたは完全に除去し、得られたペプチドを含有する発酵産物をナノろ過することにより得られる産物を含む、請求項1〜3いずれかに記載の組成物。
- カゼインの発酵により得られた小分子ペプチド Ile-Pro-Pro および/または Val-Pro-Pro 、ミネラル、生きている乳酸菌を含有する乳酸菌により発酵された組成物を含有する、請求項1〜4いずれかに記載の組成物。
- カルシウム含量が強化された、請求項1〜5いずれかに記載の組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI20020360A FI112031B (fi) | 2002-02-25 | 2002-02-25 | Biologisesti aktiivisen tuotteen uusi käyttö |
PCT/FI2002/001051 WO2003070267A1 (en) | 2002-02-25 | 2002-12-20 | Enhancing the availability of minerals by using biologically active peptides |
Publications (3)
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JP2005517424A JP2005517424A (ja) | 2005-06-16 |
JP2005517424A5 JP2005517424A5 (ja) | 2005-07-28 |
JP4242293B2 true JP4242293B2 (ja) | 2009-03-25 |
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JP2003569223A Expired - Fee Related JP4242293B2 (ja) | 2002-02-25 | 2002-12-20 | 骨の強化および骨形成を増加させるための組成物 |
Country Status (6)
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EP (1) | EP1485119A1 (ja) |
JP (1) | JP4242293B2 (ja) |
AU (1) | AU2002352303A1 (ja) |
FI (1) | FI112031B (ja) |
RU (1) | RU2004128448A (ja) |
WO (1) | WO2003070267A1 (ja) |
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WO2006004105A1 (ja) * | 2004-07-05 | 2006-01-12 | Calpis Co., Ltd. | ペプチド混合物の製造法、抗高血圧ペプチド含有発酵乳の製造法及び抗高血圧ペプチド製剤の製造法 |
ES2384096T3 (es) * | 2006-02-20 | 2012-06-29 | Compagnie Gervais Danone | Cepas de Lactobacillus helveticus que no fermentan la lactosa |
US20090111758A1 (en) | 2006-05-15 | 2009-04-30 | Valio Ltd. | Use of therapeutically useful peptides |
FI122531B (fi) * | 2009-09-30 | 2012-03-15 | Valio Oy | Juusto ja menetelmä sen valmistamiseksi |
WO2012063826A1 (ja) * | 2010-11-09 | 2012-05-18 | カルピス株式会社 | 高タンパク質分解活性を有するラクトバチルス・ヘルベティカス菌 |
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NZ183858A (en) * | 1976-12-17 | 1979-10-25 | Ashmead Hh | Polyvalent metal proteinates as food additives |
HUT52962A (en) * | 1988-03-04 | 1990-09-28 | Sandoz Ag | Process for production of medical compositions eliminating bone-absorption and promoting forming of bones |
JP3488722B2 (ja) * | 1992-03-04 | 2004-01-19 | カルピス株式会社 | カルシウム吸収促進活性剤及びその製造法 |
JP2782142B2 (ja) | 1992-07-23 | 1998-07-30 | カルピス株式会社 | アンジオテンシン変換酵素阻害剤及びその製造法 |
US6214800B1 (en) * | 1995-10-25 | 2001-04-10 | Senju Pharmaceutical Co., Ltd. | Angiogenesis inhibitor |
KR100221124B1 (ko) * | 1996-09-23 | 1999-10-01 | 한상기 | 신규한 카제인 및 그 제조방법 |
JP3028411B2 (ja) | 1997-09-26 | 2000-04-04 | カルピス株式会社 | トリペプチド高生産性ラクトバチルス・ヘルベチカス乳酸菌 |
FI113741B (fi) * | 1999-11-01 | 2004-06-15 | Valio Oy | Menetelmä verenpainetta alentavia peptidejä sisältävän tuotteen valmistamiseksi |
WO2001068115A1 (en) * | 2000-03-13 | 2001-09-20 | Monsanto Technology Llc | Process for producing peptide sequences possessing anti-hypertension activity |
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2002
- 2002-02-25 FI FI20020360A patent/FI112031B/fi not_active IP Right Cessation
- 2002-12-20 JP JP2003569223A patent/JP4242293B2/ja not_active Expired - Fee Related
- 2002-12-20 WO PCT/FI2002/001051 patent/WO2003070267A1/en active Application Filing
- 2002-12-20 RU RU2004128448/15A patent/RU2004128448A/ru not_active Application Discontinuation
- 2002-12-20 AU AU2002352303A patent/AU2002352303A1/en not_active Abandoned
- 2002-12-20 EP EP02788013A patent/EP1485119A1/en not_active Withdrawn
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JP2005517424A (ja) | 2005-06-16 |
WO2003070267A1 (en) | 2003-08-28 |
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