JP5704791B2 - 放射線療法が動物の皮膚と粘膜とに及ぼす有害な影響を低減する方法 - Google Patents
放射線療法が動物の皮膚と粘膜とに及ぼす有害な影響を低減する方法 Download PDFInfo
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- JP5704791B2 JP5704791B2 JP2008159052A JP2008159052A JP5704791B2 JP 5704791 B2 JP5704791 B2 JP 5704791B2 JP 2008159052 A JP2008159052 A JP 2008159052A JP 2008159052 A JP2008159052 A JP 2008159052A JP 5704791 B2 JP5704791 B2 JP 5704791B2
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Classifications
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- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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- A—HUMAN NECESSITIES
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- A23K20/142—Amino acids; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A23K20/158—Fatty acids; Fats; Products containing oils or fats
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Description
発明の分野
本発明は、癌に苦しんでおり放射線療法を受けている犬及び猫等の愛玩動物における皮膚と粘膜との障害を低減する方法に関し、本方法は、この目的で使用するためのフード組成物を含む。
従来技術
癌を有する動物における臨床放射線療法は、動物の正常な組織と細胞とに生化学的変化を誘発し、正常な組織と細胞とに障害を引き起こすことは周知である。放射線療法の最中の患者の正常な組織の障害を改善するための手段が、明らかに必要である。そのような改善を与えるための以前の方法は、患者に望ましくない副作用を及ぼすことがしばしばある化学薬剤を患者に投与することを含んでいる。
本発明は、癌を有し放射線療法を受けている動物の正常な細胞の放射線障害は、多価不飽和オメガ−3脂肪酸類とアルギニンとの混合物を補充した食餌を用いて動物を強化することで低減できるという発見を前提とする。
本発明によれば、癌を有する動物、特に愛玩動物における放射線療法の有害な影響を低減する方法が、そのような治療を受ける動物に、栄養素としてオメガ−6脂肪酸類を含むフード組成物であって、乾物ベースで約2.5〜約7.5%のオメガ−3脂肪酸類と約2.0〜約3.5%のアルギニンとを含み、フード中のオメガ−3脂肪酸対オメガ−6脂肪酸の重量比は約0.3:1〜3.5:1の範囲内であるようにフードの栄養素含量を補充したフード組成物を供給することで得られる。
栄養素 栄養素含量%(乾物ベース)
炭水化物 約15〜約27
タンパク質 約35〜約48
脂肪 約27〜約35
オメガ−6脂肪酸類 約2.0〜約6.0
オメガ−3脂肪酸類 約2.5〜約7.5
アルギニン 約2.0〜約3.5
栄養のバランスをとるための物質の例えば 約0.4〜約1.0
ビタミン類(A、B1、B2、B6、E)
及びミネラル類(Ca、P、Na、K、
Mg、Fe、Cl)
放射線療法による細胞障害の改善に本発明が適用可能であるような範囲において必要要件である要素は、栄養素としてオメガ−6多価不飽和脂肪酸類を含む栄養的にバランスのとれたペットフード組成物中に、上記の表Iに指定する割合で、オメガ−3多価不飽和脂肪酸類とアルギニンとの混合物が存在することである。
表II
成分 重量%
水 25〜30
肺、ビーフ肺葉 40〜45
肝臓 6〜10
鶏肉 5〜8
米 4〜8
魚油(オメガ−3及びオメガ−6脂肪酸源) 5〜8
セルロース 0.5〜2
ビーフパルプ 0.5〜2
無機塩類(炭酸カルシウム、酸化鉄、クエン酸カリウム) 0.5〜2
アルギニン 0.2〜0.6
ビタミン類 0.01〜0.2
タウリン 0.02〜0.2
ミネラル類 0.01〜0.2
本発明の実施において有用なペットフード製品を製造する際には、オメガ−6多価不飽和脂肪酸類が本ペットフード製品中に乾物ベースで約2.0〜約6.0%の濃度で存在する場合に、オメガ−3多価不飽和脂肪酸類の濃度は、本発明の動物用フード製品中に乾物ベースで約2.5〜約7.5%、好ましくは乾物ベースで約7.0〜約7.5%の濃度で存在するように栄養素組成を調節する。
実施例
ペットフード製品の製造
本発明の実施において有用なペットフード製品を製造するために、下記の表IIIに列記する諸成分の混合物をブレンドし、混合物を135°Fに15分間加熱し、続いて110°Fで缶に充填して濃厚な液体を形成し、これを缶詰にし、250°Fで83分間殺菌した。
ペットフード製品の成分組成
成分 ポンド/100ポンド
肺、ビーフ 44.00
水 26.12
肝臓、豚肉 8.00
米、パーボイルド 6.00
メンヘーデン魚油(I) 5.75
鶏肉、機械的に除骨 5.50
天然香料* 1.50
セルロース 1.00
ビーフパルプ 1.00
クエン酸カリウム 0.50
L−アルギニン 0.30
炭酸カルシウム 0.10
ビタミン混合物** 0.08
ミネラル混合物*** 0.05
タウリン 0.05
べんがら 0.03
塩化コリン 0.02
合計 100.00
*Applied Food Biotechnologiesから入手可能
**Roche Animal Health and Nutritionから入手可能
***J. M. Huber Corporationから入手可能
(I)メンヘーデン油****の脂肪酸組成 脂肪酸のwt%
パルミチン酸(16:0) 16.2
パルミトレイン酸(16:1) 11.6
ステアリン酸(18:0) 2.9
オレイン酸(18:1) 10.9
リノール酸(18:2) 1.2
リノレン酸(18:3) 1.6
オクタデカテトラエン酸(18:4) 3.2
エイコサペンタエン酸(20:5) 14.1
ドコサヘキサエン酸(22:6) 11.9
エイコサン酸(20:1) 1.3
アラキドン酸(20:4) 1.7
ドコサペンタエン酸(22:5) 2.4
****Zapata Protein, Inc.から市販されている。脂肪酸濃度<1%のものは含めない。
表IV
ペットフード製品の栄養素組成
栄養素 重量% 乾物%
水分 71.6 N/A
タンパク質 10.7 37.8
脂肪 9.3 32.6
炭水化物 6.1 21.4
繊維、粗 1.0 3.5
灰分 1.3 4.7
カルシウム 0.15 0.54
リン 0.14 0.49
ナトリウム 0.08 0.28
カリウム 0.30 1.1
マグネシウム 0.01 0.04
塩化物 0.11 0.41
オメガ−6多価不飽和脂肪酸 0.6 2.3
オメガ−3多価不飽和脂肪酸 2.07 7.3
アルギニン 0.89 3.2
癌を有し放射線療法を受けている犬に供給した場合の、正常な皮膚及び粘膜の細胞の障害の低減における表IVに説明したフード組成物の効果を決定するために、組織学的に確認された鼻腔の悪性腫瘍形成を有する12匹の犬を、ある州立大学の比較腫瘍学ユニットから抜き取った患者集団から逐次選択した。犬が悪液質であるかまたは研究のための選択の前の30日のうちに化学療法、外因性ステロイド、若くは麻酔法を受けていた場合には、こうした犬をこの研究から除外した。加えて、併発疾患の例えば腎不全、肝硬変、内分泌疾患、肥満症、または高カルシウム血症を有する犬は除外した。
表V
血清脂肪酸濃度
経過時間(単位は日)
0 7 21 42
オメガ3脂肪酸類 血清濃度(umol/L)
・ドコサヘキサエン酸(C22:6)
食餌1 1.95 21.13 18.70 22.81
食餌2 3.96 5.16 3.48 3.66
・エイコサペンタエン酸(C20:5)
食餌1 1.03 17.95 18.0 25.93
食餌2 1.16 0.80 1.02 1.10
オメガ−6脂肪酸類
・リノール酸(C18:2)
食餌1 73.92 34.45 31.26 25.96
食餌2 62.84 88.32 69.12 58.26
表Vに記録するデータは、本発明の食餌である食餌1を供給された犬は、ベースライン(0日)と及び食餌2を供給された犬と比較して、有意に(p<0.001)高い血清レベルのオメガ−3多価不飽和脂肪酸類であるドコサヘキサエン酸(C22:6)及びエイコサペンタエン酸(C20:5)と;濃度の低下したオメガ6多価不飽和脂肪酸であるリノール酸(C18:2)と;を有することを示す。
表VI
血清脂肪酸類と口腔粘膜の炎症性メディエーターとの順位相関。
口腔粘膜の
炎症性メディエーター
オメガ−3脂肪酸類 PGE2 11DTXB2
・ドコサヘキサエン酸(C22:6) 相関係数 -0.11299 -0.15750
p 0.2313 0.0942
・エイコサペンタエン酸(C20:5) 相関係数 -0.22354 -0.21390
p 0.0168 0.0223
オメガ−6脂肪酸類
・リノール酸(C18:2) 相関係数 0.04855 0.31450
p 0.6079 0.0007
表VIに記録するデータは、オメガ−3多価不飽和脂肪酸類であるドコサヘキサエン酸及びエイコサペンタエン酸の負の相関、すなわち、試料中に存在するオメガ−3脂肪酸レベルが高い程、患者が直面する炎症は低いことを示す。データはさらに、オメガ−6脂肪酸であるリノール酸の正の相関、すなわち、オメガ−6多価不飽和脂肪酸レベルが高い程、メディエーターレベルが高く、患者が直面する炎症は高いことを示す。
表VII
血清脂肪酸類と皮膚の炎症性メディエーターとの順位相関。
皮膚の
炎症性メディエーター
オメガ−3脂肪酸類 PGE2 11DTXB2
・ドコサヘキサエン酸(C22:6) 相関係数 -0.13259 -0.16783
p 0.01596 0.0769
・エイコサペンタエン酸(C20:5) 相関係数 -0.2729 -0.16456
p 0.0040 0.0829
オメガ−6脂肪酸類
・リノール酸(C18:2) 相関係数 0.15504 0.23658
p 0.0995 0.0120
表VIIに記録するデータは、高いレベルのオメガ−3脂肪酸類であるエイコサペンタエン酸及びドコサヘキサエン酸を用いた患者においては、炎症性メディエーターの皮膚濃度は、順位相関によって有意に低いことを示す。より低い濃度の炎症性メディエーターは、放射線療法の急性副作用を改善する際に役割を果たすと考えられている。
血清脂肪酸類と口腔粘膜細胞の組織学スコアとの順位相関。
口腔粘膜細胞の
組織学スコア
オメガ−3脂肪酸類
・ドコサヘキサエン酸(C22:6) 相関係数 0.25664
p 0.0171
・エイコサペンタエン酸(C20:5) 相関係数 0.24314
p 0.0241
オメガ−6脂肪酸類
・リノール酸(C18:2) 相関係数 -0.13776
p 0.2059
表VIIIに記録するデータは、総合で最高のエイコサペンタエン酸及びドコサヘキサエン酸血清濃度を有する患者は、粘膜領域内の細胞層厚さの最良の組織学スコアを有することを示しており、これは粘膜炎の低減に対処するものであると、従って、放射線療法を受けている患者のクオリティオブライフを改良すると考えられている。
血清脂肪酸類と臨床成績状況との順位相関。
臨床成績
オメガ−3脂肪酸類
・ドコサヘキサエン酸(C22:6) 相関係数 -0.36840
p 0.0139
・エイコサペンタエン酸(C20:5) 相関係数 -0.31893
p 0.0349
オメガ−6脂肪酸類
・リノール酸(C18:2) 相関係数 0.22244
p 0.1467
表V〜VIIIに記録したデータを得た分析の手順を下記に説明する。
脂肪酸の分析
脂肪酸類は、Ohta A, Mayo M C, Kramer N, Lands WE. Rapid analysis of fatty acids in plasma lipids. Lipids 1990; 25: 742-747に説明するように、Zicker et alの手順に従って分析した。
組織病理学
口腔粘膜及び皮膚の、コンピュータ化治療計画によって決定した低(200cGy)及び高(300cGy)放射線量を受けている領域内で、6mmのBaker’s生検用パンチを用いて生検用に採取をした。生検は、治療の前の1週間、治療開始から1日後、治療開始から7日後、治療の終り、及び治療終了後21日に実行した。1人の病理学者が、細胞層厚さに関して組織病理学的に組織を評価した。
炎症性メディエーターの分析
低及び高放射線量を受けている領域の口腔粘膜及び皮膚を、組織病理学の場合と同じようにして得、−80℃で凍結させた。凍結した試料を清浄なガラススライド上に置き、解凍が起きる前に小さな断片に切り分けた。切り分けた断片を4mlのプラスチック培養管に移し、2mlの低温の酢酸エチルを加えた。試料を次に最高速度の設定で1分間均質化し、その間、試料及び培養管を氷浴中に置いた。次いで試料及び培養管をホモジナイザーから取り出し、ホモジナイザーの先端を1mlの低温の酢酸エチルを用いて濯いだ。濯ぎ液と試料を合わせた。培養管にアルミニウム箔を用いて蓋をし、氷浴中に30分間置いた。氷浴中に30分置いた後に管に蓋をし、500gで10分間、5℃で遠心分離した。全ての上澄みを除去し、新たな4mlのプラスチック培養管中に入れた。窒素ガスの遅い流れを用いて酢酸エチルを試料から蒸発させた。湯浴(30℃)を使用して乾燥を促進した。試料残留分を500ulのEIA緩衝液(Caymen, Ann Arbor, MI)中に再懸濁した。試料を窒素ガスで覆い、−80℃で保管した。酵素免疫測定法キット(Caymen, Ann Arbor, MI)を用いて、プロスタグランジンE2及び11−デヒドロ−トロンボキサンB2に関して試料を分析した。
Claims (2)
- 癌を有し放射線療法を受けているイヌの皮膚と粘膜の細胞への放射線療法に起因する有害な影響を軽減する方法であって、オメガ−6多価不飽和脂肪酸類と、オメガ−3多価不飽和脂肪酸類とアルギニンとの混合物とを含む栄養的にバランスのとれたペットフードを供給することと、少なくとも前記イヌが放射線にさらされる期間の間中、前記イヌに前記フードを供給することと、を含む方法において、アルギニンは、前記フード中に乾物ベースで2.0〜3.5%の濃度で存在し、前記オメガ−6多価不飽和脂肪酸類は、前記フード中に乾物ベースで2.0〜6.0%の濃度で存在し、前記オメガ−3多価不飽和脂肪酸類は、前記フード中に乾物ベースで7.0〜7.5%の濃度で存在し、前記フード中に存在するオメガ−3多価不飽和脂肪酸類対オメガ−6脂肪酸類の重量比は0.3:1〜3.5:1である、方法。
- 前記フードは、27〜35重量%の脂肪、15〜27重量%の炭水化物、及び35〜48%のタンパク質を含む、請求項1に記載の方法。
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US09/106,295 US6015798A (en) | 1995-10-10 | 1998-06-29 | Method for reducing the damaging effects of radiation therapy on animal skin and mucosa |
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JP2008159052A Expired - Lifetime JP5704791B2 (ja) | 1998-06-29 | 2008-06-18 | 放射線療法が動物の皮膚と粘膜とに及ぼす有害な影響を低減する方法 |
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US (1) | US6015798A (ja) |
EP (1) | EP1091734B1 (ja) |
JP (2) | JP4860814B2 (ja) |
AR (1) | AR019728A1 (ja) |
AT (1) | ATE249821T1 (ja) |
AU (1) | AU761266B2 (ja) |
BR (1) | BR9911663A (ja) |
CA (1) | CA2336628C (ja) |
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MX (1) | MXPA01000152A (ja) |
NO (1) | NO329910B1 (ja) |
NZ (1) | NZ508766A (ja) |
TR (1) | TR200100457T2 (ja) |
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WO2001091575A1 (en) | 2000-06-01 | 2001-12-06 | United Feeds, Inc. | Animal food and method |
EP1350435B1 (en) | 2002-04-05 | 2010-12-22 | Societe Des Produits Nestle S.A. | Compositions and methods for promoting lipid assimilation in pets |
US8841344B2 (en) * | 2002-10-03 | 2014-09-23 | Hill's Pet Nutrition, Inc. | Method of using omega-3 fatty acids |
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US20060204636A1 (en) * | 2002-12-23 | 2006-09-14 | Butterwick Richard F | Food for gastrointestinal health |
GB0311081D0 (en) * | 2003-05-14 | 2003-06-18 | Btg Internat Limted | Treatment of neurodegenerative conditions |
WO2005018630A1 (en) * | 2003-08-11 | 2005-03-03 | Hill's Pet Nutrition, Inc. | Omega-3 fatty acids for the treatment of canine ostheoarthritis |
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DE112004001520B4 (de) * | 2003-08-18 | 2008-04-10 | Btg International Ltd. | Verwendung eines Lipidglyzerids festgelegter Struktur zur Herstellung eines Medikamentes zur Behandlung der multiplen Sklerose |
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US20070031534A1 (en) * | 2004-02-27 | 2007-02-08 | Hajime Tsujimoto | Pet food for reducing food allergy reactions |
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US6015798A (en) * | 1995-10-10 | 2000-01-18 | Colgate Palmolive Company | Method for reducing the damaging effects of radiation therapy on animal skin and mucosa |
US5776913A (en) * | 1995-10-10 | 1998-07-07 | Colgate Palmolive Company | Therapeutic diet for metabolic abnormalities found in animals with lymphoma |
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AU761266B2 (en) | 2003-05-29 |
ES2207951T3 (es) | 2004-06-01 |
DE69911409T2 (de) | 2004-07-08 |
US6015798A (en) | 2000-01-18 |
AR019728A1 (es) | 2002-03-13 |
DE69911409D1 (de) | 2003-10-23 |
BR9911663A (pt) | 2005-12-20 |
EP1091734B1 (en) | 2003-09-17 |
MXPA01000152A (es) | 2002-10-17 |
ATE249821T1 (de) | 2003-10-15 |
CA2336628C (en) | 2009-03-24 |
JP4860814B2 (ja) | 2012-01-25 |
AU4716799A (en) | 2000-01-17 |
TR200100457T2 (tr) | 2001-08-21 |
NO329910B1 (no) | 2011-01-24 |
NZ508766A (en) | 2003-05-30 |
NO20006575L (no) | 2001-02-28 |
ZA200007650B (en) | 2002-08-28 |
DK1091734T3 (da) | 2004-01-26 |
JP2002519320A (ja) | 2002-07-02 |
JP2009035533A (ja) | 2009-02-19 |
EP1091734A1 (en) | 2001-04-18 |
CA2336628A1 (en) | 2000-01-06 |
WO2000000189A1 (en) | 2000-01-06 |
NO20006575D0 (no) | 2000-12-21 |
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