JP7402826B2 - がん悪液質において用いる化合物 - Google Patents
がん悪液質において用いる化合物 Download PDFInfo
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- JP7402826B2 JP7402826B2 JP2020567530A JP2020567530A JP7402826B2 JP 7402826 B2 JP7402826 B2 JP 7402826B2 JP 2020567530 A JP2020567530 A JP 2020567530A JP 2020567530 A JP2020567530 A JP 2020567530A JP 7402826 B2 JP7402826 B2 JP 7402826B2
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- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
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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
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- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Description
-R1は、5個以下の-OR2置換基があるC1-C6アルキル基であり、ここで、R2は水素、若しくはC1-C6アルキル、又は、OR2は(R)-3-ヒドロキシ酪酸部分を表し;又は
-R1は、アルコールHOR1に由来する部分であり、ここで前記アルコールは糖である)
である化合物、又はその医薬的に許容可能な塩若しくは溶媒和物を提供する。
-R1は、5個以下の-OR2置換基があるC1-C6アルキル基であり、ここで、R2は水素、若しくはC1-C6アルキル、又は、OR2は(R)-3-ヒドロキシ酪酸部分を表し;又は
-R1は、アルコールHOR1に由来する部分であり、ここで前記アルコールは糖である)
、又はその医薬的に許容可能な塩若しくは溶媒和物であり;
ここで、化合物の投与1時間後に、被験体における(R)-3-ヒドロキシ酪酸塩の血中濃度は、1~20mMの範囲内である。
上記で特定された一般式Iの化合物の治療有効量を、被験体に投与することを含む、前記被験体におけるがん性悪液質の治療方法;
以下の式:
化合物の投与1時間後に、被験体における(R)-3-ヒドロキシ酪酸塩の血中濃度は、1~20mMの範囲内である、前記被験体に上記一般式Iの化合物の治療有効量を投与することを含む、前記被験体におけるがんの治療方法;
被験体におけるがん性悪液質の治療用医薬の製造における、上記で特定された一般式Iの化合物の使用;
被験体におけるがん性悪液質の治療用医薬の製造における、以下の式:
-R1は、5個以下の-OR2置換基があるC1-C6アルキル基であり、ここで、R2は水素、若しくはC1-C6アルキル、又は、OR2は(R)-3-ヒドロキシ酪酸部分を表し;又は
-R1は、アルコールHOR1に由来する部分であり、ここで前記アルコールは糖である)である。
- 希釈剤、例えばラクトース、デキストロース、サッカロース、セルロース、トウモロコシデンプン又はジャガイモデンプン;
- シリカ、タルク、ステアリン酸、ステアリン酸マグネシウム又はステアリン酸カルシウム及び/又はポリエチレングリコール等の潤滑剤;
- デンプン、アラビアゴム、ゼラチン、メチルセルロース、カルボキシメチルセルロース、又はポリビニルピロリドン等の結合剤;
- デンプン、アルギン酸、アルギン酸塩又はデンプングリコール酸ナトリウム等の崩壊剤;
- 発泡剤;
- 染料;
- フレーバー;
- 湿潤剤、例えば、レシチン、ポリソルベート、ラウリル硫酸塩;及び/又は
- キャリア
組成物が液体形態である場合、組成物は、本明細書中で特定される化合物等を、液体組成物の少なくとも1質量%、例えば3~40質量%のレベルで含むのが適当であるが、組成物が、所望の血中ケトンレベルに達するように、単回投与として受け取ることが意図されるのか、又は複数回のより小さな用量として受け取ることが意図されるのかに応じて、組成物の例えば50質量%まで高くすることができる。
組成物(医薬的及び栄養学的ともに)は、医薬的に許容される吸着剤を含み得る。好適には、吸着体は、吸着体内又は吸着体上に本発明の化合物を吸着する。有利には、化合物の香味(嫌味かもしれない)は、吸着剤なしで同じ組成物を消費した場合に経験されるよりも、使用者が経験するレベルが低い。好ましくは、前記吸着体は、本発明の化合物を保持することができる格子又はボイドを含む。食品に使用又は使用することが知られているいかなる吸着剤を使用することができる。好適な吸着剤の例としては、ポリマーヒドロゲル、例えば架橋ポリカルボキシレートホモポリマー又はコポリマーのポリマー、包接化合物、環状オリゴ糖、例えばシクロデキストリン、及び乳粉末が挙げられる。吸着体は、特定の処方に従っていかなる所望のレベルで存在することができ、組成物の5質量%~80質量%、例えば、10質量%~50質量%であり得る。
動物飼育形態及び飼育 - 11週齢の雄Balb/cマウスを入手し、室温(21~23℃)及び湿度(40~60%)の制御条件下で午前6時~午後6時の光サイクルでポリカーボネートケージに収容した。マウスを個別に飼育して、個々のエネルギー摂取量及び身体活動パラメータを評価した。ケージにはトウヒの粒子(Lignocel(登録商標)BK8/15)の敷物が含まれ、3週間ごとに交換した。濃縮は、ケージ交換時に交換した2つの綿ペレットで行った。流動食を与えている間、マウスに木製の棒を1本与えて、歯を正しく磨耗させた。固形食はケージの頂部の金属ワイヤ蓋の凹部に供給し、液体食は供給チューブ(Bio-ServTM、カタログ#14-726-518)により毎日供給した。ケージ内に延伸する金属ディスペンサを備えた集中システムによって水を供給した。全ての手順は、ベルギーのKU Leuven動物倫理委員会によって承認された(P093/2017)。
表1:実験飼料の多量栄養素組成
生存実験 - 40匹のマウスを、初期体重に基づいて様々な実験群に無作為に割り付け、上記のように処置した。マウスの寿命を延ばし、瀕死状態と考えられた場合にのみ安楽死させた。体重、摂餌量及び車輪走行パラメータを毎日測定した。生存期間に対する交絡作用を避けるため、追加測定は行わなかった。
行動試験及び組織採取実験- 第2実験では、各実験群に9匹のマウスを含め、行動試験及び組織採取に用いた。マウスは、PBS又は腫瘍細胞接種の16日後に安楽死させた。測定した変数に対する運動の潜在的な急性効果を排除するために、走行輪を犠牲にする24時間前に除去した。
体重、摂餌量及び車輪走行パラメータ-体重は、食品トレーニング期間中3日毎に測定した。腫瘍誘発後、体重を4日間隔で測定した。摂餌量及び車輪走行パラメータを毎日測定した。
図1は生存期間を示し、図1(A)は5つの実験群すべての生存曲線を示す。図1(B)は運動状態の主な影響を示す(CONrest&KETrest vs.CONEX&KETEX)。図1(C)は栄養状態の主な影響を示す(CONrest+CONWR vs.KETrest + KETEX)。ケトン群のマウスは、対照群と比較して、生存期間の平均及び中央値が大幅に増加した(それぞれ+40%及び+17%、p<0.01)。生存率は、安静群と運動群で同程度であった。
表2:対照飼料又はケトンエステル飼料のいずれかを摂取した場合のマウスホイールの走行活動
Claims (9)
- 被験体は、がんに罹患している、請求項1に記載の医薬組成物。
- がんは、結腸がんである、請求項2に記載の医薬組成物。
- 化合物は、さらに、腫瘍増殖の抑制に用いられる、請求項2又は3に記載の医薬組成物。
- 化合物は、さらに、被験体の生存促進に用いられる、請求項1~4のいずれか一項に記載の医薬組成物。
- 化合物は、さらに、被験体の筋肉量の維持又は増加に用いられる、請求項1~5のいずれか一項に記載の医薬組成物。
- 化合物は、さらに、被験体の活性レベルの維持又は増加に用いられる、請求項1~6のいずれか一項に記載の医薬組成物。
- 炭水化物化合物、又は、グルコース、フルクトース又はマルトースのような単純糖、と併用される、請求項1~7のいずれか一項に記載の医薬組成物。
- さらに、1又はそれ以上の医薬的に許容される賦形剤、香味剤、タンパク質、炭水化物、糖類、脂肪、繊維、ビタミン類及びミネラル類、中鎖トリグリセリドを含み、前記中鎖トリグリセリドは、式CH2Ra-CHRb-CH2Rc(式中、Ra、Rb及びRcの炭素原子は5~12個である脂肪酸である)を備える、請求項1~8のいずれか一項に記載の医薬組成物。
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GB1809113.2A GB2575623B (en) | 2018-06-04 | 2018-06-04 | 3-hydroxybutyrate esters for treating cancer cachexia |
GB1809113.2 | 2018-06-04 | ||
PCT/GB2019/051532 WO2019234402A1 (en) | 2018-06-04 | 2019-06-03 | Compounds for use in cancer cachexia |
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CA3102503A1 (en) | 2019-12-12 |
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