JP6904589B2 - 抗ストレス、抗不安及び抗うつ活性を有する薬剤、並びにそれに基づく組成物 - Google Patents
抗ストレス、抗不安及び抗うつ活性を有する薬剤、並びにそれに基づく組成物 Download PDFInfo
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- JP6904589B2 JP6904589B2 JP2018521213A JP2018521213A JP6904589B2 JP 6904589 B2 JP6904589 B2 JP 6904589B2 JP 2018521213 A JP2018521213 A JP 2018521213A JP 2018521213 A JP2018521213 A JP 2018521213A JP 6904589 B2 JP6904589 B2 JP 6904589B2
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- lithium
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- ascorbic acid
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Description
アスコルビン酸リチウム:10〜90%;
ピリドキシン塩酸塩:6〜50%;
チアミン硝酸塩:4〜40%;
は、本組成物において用いられることが好ましい。
第1群−対照(ラットには水を投与する);
第2群−実験、アスコルビン酸リチウム投与量120mg/動物の体重kg;
第3群−実験、アスコルビン酸リチウム投与量60mg/動物の体重kg;
第4群−実験、アスコルビン酸リチウム投与量30mg/動物の体重kg;
第5群−未処置ラット(試験に関与せず、動物飼育場で飼育するのと同じ条件下で自然に発育した);
第6群−実験、アスコルビン酸リチウム投与量60mg/動物の体重kg、錠剤で投与(錠剤は総質量0.2〜0.25gであり、カカオ脂を賦形剤として用いた)。
試験中、製剤の長期投与を行う動物の反応変化を観察した。3つの実験シーケンスを7日周期で実施した。薬剤を試験初日から中断無く毎日投与した。こうして、動物の体内に薬剤が蓄積した。各群から5匹の動物を実験の各シーケンスに用いた(動物を24時間つり下げた)。この後、血液サンプルを舌下血管から採取した。さらに、動物をジエチルエーテルで安楽死させた。断頭及び腹腔切開を行って、胃内面の潰瘍数を算出した。向精神薬の試験対象として、ラットは成功したモデルである。ラットは様々なストレス因子に直ちに反応する。生理的、行動的、生化学的及び他のパラメータに始まる様々な因子により、薬剤の効能を評価するのは都合がよい。懸垂試験において、身体持久力に加えて、動物の全体的な精神情動状態を測定することができる。
輸送ストレスをシミュレーションするためのモデルとして回転式万能撹拌機Unimax10を用いた。回転速度を120rpm、240分で選択した。5匹の動物が入るケージをその場に固定した。ラットはケージ中で自由な状態であった。薬剤の長期投与に伴う動物の反応変化を観察した。サンプリング及び断頭プロセスは実施例1に記載する。
実験動物の身体中にアスコルビン酸リチウムが蓄積する間、ストレスに対する身体応答は、少なくとも試験した投与量範囲においては、投与量にそれほど依存しなかった。投与量30mg/体重kgは、投与量60mg/kgの効能をわずかに上回った。投与量120mg/kgの効果は弱かった。さらに、第2及び第3試験(調査開始14日目及び21日目)では、投与量30mg/kg及び120mg/kgで得られた結果が、平均3%〜10%の有意差を示した(表1、2、3)。従って、アスコルビン酸リチウムは少量でより効果的であると結論付けることができる。
試験群の1つには、60mg/kgの投与量で(賦形剤としてカカオ脂を含む)錠剤状の製剤を投与した。この変形体はストレスが少ない投与形態、及び長期持続型のリチウム効果を示唆した。得られた結果(表1〜5)は、リチウム蓄積速度が経口投与した同じ投与量の水性液剤と比べて遅かったことを示唆している。この投与形態の7日目の活性はより低かった。しかし、投与14日及び21日目には、カカオ脂を含む塊状(錠剤)のアスコルビン酸リチウムを摂取する動物の状態は、未処置動物に匹敵し、一部の例では、アスコルビン酸リチウム液剤の経口投与で得られた結果を上回った。従って、持続形態の効果は長期暴露で有効であると考えられ、特徴としてアスコルビン酸リチウムの蓄積、及び代謝に対する長期にわたる有益な効果が挙げられる。第6群動物の体重増加及び血液クレアチニンの増加は筋肉量増加を示す。ジストロフィーを引き起こし得る身体のるい痩は無かった。様々な病因のストレスに対する身体の適切な応答、身体のエネルギー貯蔵の蓄積は、皮下脂肪(脂肪組織)が急激に増加すること無く、筋組織を増加させた。従って、動物はストレスにも関わらず、成長発達した。
液剤形態アスコルビン酸リチウム製剤の急性毒性パラメータを試験した。体重180.0〜200.0gの4ヶ月齢雄性ウィスターラットに対して実験を行った。動物を選択し、対の類似体の原則に従って群に分け、同一の摂餌、管理条件下に置いた。
第(1)群には10%アスコルビン酸リチウム、55%ビタミンB6、35%ビタミンB1を投与した。
第(2)群−50%アスコルビン酸リチウム、30%ビタミンB6、20%ビタミンB1。
第(3)群−65%アスコルビン酸リチウム、20%ビタミンB6、15%ビタミンB1。
第(4)群−90%アスコルビン酸リチウム、6%ビタミンB6、4%ビタミンB1。
第(5)群−対照群には注射用水のみを投与した。
実験及び対照群で得られた結果を比較すると、組成物が上記活性を示すことと;
組成物における活性薬剤比の有効範囲は相当広いが、組成物の最大効能は65%アスコルビン酸リチウム、20%ビタミンB6及び15%ビタミンB1の比で得られることとと;
組成物の効能はアスコルビン酸リチウム割合の増加及びビタミン割合の減少、並びにビタミン割合の増加及びアスコルビン酸リチウム割合の減少に伴い低下したため、組成物に用いられるこれらの物質の相乗効果を示唆することと、を示す。
Claims (7)
- ストレス、不安又はうつ病を患う患者を治療する薬剤を調製するための組成物の使用であって、前記組成物がアスコルビン酸リチウムを含む、使用。
- 前記組成物がビタミンB6及びビタミンB1をさらに含む、請求項1に記載の使用。
- 請求項2に記載の使用であって、前記組成物の前記成分が以下の質量パーセント比:
10〜90%アスコルビン酸リチウム;
6〜50%ビタミンB6;
4〜40%ビタミンB1、
で前記組成物に含まれる、使用。 - 請求項3に記載の使用であって、前記組成物がカカオ脂、ソルビトール、マルトデキストリン、タルク及びカフォスからなる群から選択される少なくとも1つの補助的な賦形剤をさらに含む、使用。
- 請求項3に記載の使用であって、前記組成物が補助的な賦形剤としてカカオ脂をさらに含む、使用。
- ストレス、不安又はうつ病を患う患者におけるストレス、不安又はうつ病の症状及び程度を緩和する薬剤、又は栄養補助食品、又はサプリメントを調製するための組成物の使用であって、前記組成物がアスコルビン酸リチウムを含む、使用。
- 請求項6に記載の使用であって、前記組成物がビタミンB6及びビタミンB1をさらに含み、前記組成物の前記成分が以下の質量パーセント比:
10〜90%アスコルビン酸リチウム;
6〜50%ビタミンB6;
4〜40%ビタミンB1、
で前記組成物に含まれる、使用。
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PCT/RU2016/050049 WO2017069662A1 (ru) | 2015-10-23 | 2016-10-10 | Средство с антистрессовой, анксиолитической и антидепрессивной активностью и композиция на его основе |
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FR2193585B1 (ja) * | 1972-07-28 | 1975-08-08 | Bohuon Claude | |
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JPH06192087A (ja) * | 1992-10-02 | 1994-07-12 | Takeda Chem Ind Ltd | 感情障害改善・治療剤 |
JP3942207B2 (ja) * | 1995-02-17 | 2007-07-11 | 武田薬品工業株式会社 | うつ性症状改善剤 |
JP2002520353A (ja) | 1998-07-16 | 2002-07-09 | マサチューセッツ インスティテュート オブ テクノロジー | ストレスの処置のための組成物 |
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US10849878B2 (en) | 2020-12-01 |
US10456373B2 (en) | 2019-10-29 |
EP3366288B1 (en) | 2023-12-27 |
EP3366288A1 (en) | 2018-08-29 |
ZA201803399B (en) | 2021-07-28 |
US20200009111A1 (en) | 2020-01-09 |
US20180228766A1 (en) | 2018-08-16 |
CN108348500A (zh) | 2018-07-31 |
JP2018535957A (ja) | 2018-12-06 |
EA201800218A1 (ru) | 2019-03-29 |
WO2017069662A1 (ru) | 2017-04-27 |
PL3366288T3 (pl) | 2024-05-06 |
EP3366288C0 (en) | 2023-12-27 |
CN117243957A (zh) | 2023-12-19 |
RS65481B1 (sr) | 2024-05-31 |
UA123730C2 (uk) | 2021-05-26 |
EP3366288A4 (en) | 2019-06-26 |
KR20180067685A (ko) | 2018-06-20 |
RU2617512C1 (ru) | 2017-04-25 |
MA45974A (fr) | 2021-05-26 |
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