JPS62135420A - Amino acid transfusion solution - Google Patents
Amino acid transfusion solutionInfo
- Publication number
- JPS62135420A JPS62135420A JP27643285A JP27643285A JPS62135420A JP S62135420 A JPS62135420 A JP S62135420A JP 27643285 A JP27643285 A JP 27643285A JP 27643285 A JP27643285 A JP 27643285A JP S62135420 A JPS62135420 A JP S62135420A
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- transfusion solution
- amino acids
- solution
- valine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、L−バリンを含まない点用アミノ酸輸液に関
する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a topical amino acid infusion that does not contain L-valine.
特定のアミノ酸を含まない若しくは過剰に配合したアミ
ノ酸製剤の癌増殖抑制作用に関する研究は近年盛んに行
われ、効果ありとする具体的処方についても種々提案さ
れている。例えば、特開昭55−35049にはメチオ
ニンを含まない6〜10種のアミノ酸からなる点用アミ
ノ酸輸液が、DE−3329253(AI)には必須及
び準必須アミノ酸の1種又は2種以上を含まない14〜
17種のアミノ酸からなる点用アミノ酸組成物がそれぞ
れ開示されている。In recent years, research has been actively conducted on the cancer growth-inhibiting effects of amino acid preparations that do not contain specific amino acids or that contain excess amounts of specific amino acids, and various specific formulations that are effective have been proposed. For example, JP-A-55-35049 discloses a topical amino acid infusion consisting of 6 to 10 amino acids that does not contain methionine, and DE-3329253 (AI) contains one or more essential and semi-essential amino acids. No 14~
A topical amino acid composition consisting of 17 types of amino acids is disclosed.
しかし、特定のアミノ酸を単に欠乏させ若しくは過剰に
配合することによって一様の癌増殖1rll制効果が得
られるとは限らず、その効果及び生体への栄養効果は投
与する全アミノ酸成分の配合割合に大きく依存する。し
たがって最適の点用アミノ酸組成を見出すことは容易で
はなく、未だ著効を示す点用アミノ酸製剤は開発されて
いない。However, it is not always possible to obtain a uniform cancer growth inhibiting effect by simply depleting or adding an excess of a specific amino acid, and its effect and nutritional effect on the living body depend on the proportion of all amino acid components administered. Much depends. Therefore, it is not easy to find the optimal amino acid composition for topical use, and no topical amino acid formulation showing significant efficacy has yet been developed.
C問題点を解決するための手段及び作用〕前記特開昭5
5−35049、DIF、−5329253(Al)を
はじめとする公知の点用アミノ酸組成は、いずれも健常
人の血中アミノ酸パターン(健常パターン)と大きく相
違しているのに対し、本発明者らは、「健常パターンに
返信したアミノ酸組成から最小限のアミノ酸を除くこと
によって、より選択的に癌の増殖を抑制することが可能
」との観点に立ち、鋭意研究した結果、所間の目的を達
成する本発明を完成することができた。Means and action for solving problem C] Said Japanese Unexamined Patent Publication No. 5
The amino acid compositions of known topical amino acids, including 5-35049, DIF, and -5329253 (Al), are all significantly different from the blood amino acid patterns of healthy individuals (healthy patterns). As a result of intensive research, we have determined that cancer growth can be suppressed more selectively by removing the minimum number of amino acids from the amino acid composition that corresponds to the healthy pattern. We were able to complete the present invention.
すなわち、本発明は、L−バリンを含まないアミノ酸組
成であって、少なくとも下記アミノ酸を下記組成範囲内
で含有することを特徴とする。That is, the present invention is characterized by an amino acid composition that does not contain L-valine and contains at least the following amino acids within the following composition range.
アミノ酸 組成範囲
(g/全アミノ酸100g )
L−イソロイシン 5.25〜6.41L−ロイ
シン 11.71〜14.31L−リジン
8.24〜10.08L−メチオニン
3.28〜4,01L−フェニルアラニン 8.
76〜10.71L−)レオニン 6.09〜
7.44L−トリプトファン 1.22〜1.49
L−アラニン 5.81〜7.11L−アル
ギニン 7,41〜9.05L−アスパラギン
酸 3.56〜4.35L−システイン
0.93〜1.14し一グルタミン酸 6.08
〜7.44L−ヒスチジン 6.14〜7.5
0L−プロリン 3.09〜3.78L−
セリン 2.06〜2.52し一千ロジン
0.33〜0.407ミノ酢酸
10.03〜12.25本発明に用いるアミノ酸は
、遊離型のみならず薬理学的に許容される塩、例えばナ
トリウム塩等の金属塩、塩酸塩等の鉱酸塩若しくは酢酸
塩等の有機酸塩の形で使用することができる。Amino acid composition range (g/100g of total amino acids) L-isoleucine 5.25-6.41L-leucine 11.71-14.31L-lysine
8.24-10.08L-methionine
3.28-4,01L-phenylalanine 8.
76~10.71L-)Leonine 6.09~
7.44L-tryptophan 1.22-1.49
L-alanine 5.81-7.11L-arginine 7,41-9.05L-aspartic acid 3.56-4.35L-cysteine
0.93-1.14 monoglutamic acid 6.08
~7.44L-Histidine 6.14-7.5
0L-Proline 3.09-3.78L-
Serine 2.06-2.52 1,000 rosin 0.33-0.407 aminoacetic acid
10.03-12.25 The amino acids used in the present invention can be used not only in free form but also in pharmacologically acceptable salts, such as metal salts such as sodium salts, mineral acid salts such as hydrochloride, or organic acids such as acetate. Can be used in salt form.
本発明輸液のアミノ酸濃度は、溶解度の範囲内で特に制
限はないが、4〜12%程度、好ましくは5〜lO%で
ある。また、pl+の好ましい範囲は5.0〜7.8、
より好ましくは6.0〜7.5である。The amino acid concentration of the inventive infusion is not particularly limited within the range of solubility, but is approximately 4 to 12%, preferably 5 to 10%. Further, the preferable range of pl+ is 5.0 to 7.8,
More preferably it is 6.0 to 7.5.
本発明輸液には、必要に応じてtJ!質、電解質、ビタ
ミン等を添加することができる。The infusion of the present invention may include tJ! Substances, electrolytes, vitamins, etc. can be added.
本発明輸液を製造するに際し、特に困デ「はなく既存の
アミノ酸輸液の製造方法に準拠すればよい。There are no particular difficulties in producing the infusion of the present invention, and existing methods for producing amino acid infusions may be followed.
上記の如くして得られる本発明輸液は、中心静脈若しく
は末梢血管から注入され、場合によっては経腸投与も可
能である。投与量は、通常10当たり300=1800
mA’の範囲で、アミノ酸濃度、患者の体重、病態等に
応して適宜増減すればよい。The infusion solution of the present invention obtained as described above can be injected through the central vein or peripheral blood vessels, and can also be administered enterally in some cases. The dosage is usually 300 per 10 = 1800
It may be increased or decreased as appropriate within the range of mA' depending on the amino acid concentration, patient's weight, pathological condition, etc.
〔実施例1〕
下記アミノ酸を下記濃度で注射用蒸留水に溶かしp I
tを中性付近に調整後、除菌濾過する。次いでこの溶液
をバイアルビン又は合成樹脂製バッグに充填し、空間部
を窒素直換後密栓し、常法により加熱滅菌して目的のし
一バリン欠乏アミノ酸輸液を得る。[Example 1] The following amino acids were dissolved in distilled water for injection at the following concentration.
After adjusting t to around neutrality, sterilization and filtration are performed. Next, this solution is filled into a vial or a synthetic resin bag, the space is sealed after direct nitrogen exchange, and the solution is heat sterilized by a conventional method to obtain the desired valine-deficient amino acid infusion.
アミノ酸 g/IL−イ
ソロイシン 5.60L−ロイシン
12’、50L−リジン・lIc1
11.0OL−メチオニン
3.50L−フェニルアラニン
9.35L−)レオニン 6.5
0Llリブトファン ゛ 1.3OL−
アラニン 6.2OL−アルギニ
ン・IIcI 9.55L−アスパラ
ギン酸 3.8OL−システイン・l
lCl ・11□Ol、45L−グルタミン酸
6.50L−ヒスチジン・IIcI
・lho 8.11L−プロリン
3.30L−セリン
2.20L−チロシン 0.
357ミノ酢酸 10.70遊離
アミノ酸としての全量 95.49〔参考例1〜
5〕
下記アミノ酸を下記濃度で実施例1と同様に処理して、
L−トリプトファン、L−メチオニン・L−システイン
、L−フェニルアラニン・L−チロシン、又はL−ロイ
シン欠乏のアミノMla液(参考例1〜4)及び対照液
(参考例5)を得、以下の実験に供した。Amino acid g/IL-isoleucine 5.60L-leucine
12', 50L-lysine lIc1
11.0OL-Methionine
3.50L-phenylalanine
9.35L-) leonine 6.5
0Ll ribtofan ゛ 1.3OL-
Alanine 6.2OL-Arginine・IIcI 9.55L-Aspartic acid 3.8OL-Cysteine・L
lCl ・11□Ol, 45L-glutamic acid
6.50L-Histidine IIcI
・lho 8.11L-proline
3.30L-Serine
2.20L-tyrosine 0.
357 Minoacetic acid 10.70 Total amount as free amino acid 95.49 [Reference example 1~
5] The following amino acids were treated in the same manner as in Example 1 at the following concentrations,
Amino Mla solutions lacking L-tryptophan, L-methionine/L-cysteine, L-phenylalanine/L-tyrosine, or L-leucine (Reference Examples 1 to 4) and a control solution (Reference Example 5) were obtained, and the following experiments were conducted. Served.
以下、試験例により本発明の効果を示す。 The effects of the present invention will be shown below with test examples.
試験例1
体ffi 180 g前後のドンリュウ系う、ト(各群
4〜7匹)に腹水肝癌Al1109Aの細胞を5×10
6咽/匹皮下移植した。Test Example 1 Ascites liver cancer Al1109A cells were injected into 5 x 10 Donryu animals (4 to 7 animals in each group) weighing around 180 g.
Six pharynx/mouse were subcutaneously transplanted.
移植後5日目より6又は8日間、中心静脈栄養法を用い
て実施例1及び参考例I〜5をそれぞれ基本液とした栄
養輸液(投与全熱量の90%:基本液にグルコースと蒸
留水を加え最終的にアミノ酸濃度5−/v%、グルコー
ス(濃度27w/v%とした液。残り10%の熱ffi
: 10w/v%脂肪乳剤)を300〜400 c
a 17’Kg/日持続投与した。For 6 or 8 days from the 5th day after transplantation, nutritional infusion using Example 1 and Reference Examples I to 5 as the base solution using central parenteral nutrition (90% of the total caloric amount administered: glucose and distilled water as the base solution) was added to give a final amino acid concentration of 5-/v% and glucose (concentration of 27 w/v%).The remaining 10% was heated to
: 10w/v% fat emulsion) at 300-400c
a Continuous administration of 17'Kg/day.
投与最終日に各群の腫瘍組織を摘出し重量を測定、次い
で下式に基づき各群の対照(参考例5)群に対する腫瘍
増殖率を〕γ出し第1表の結果を11だ。On the final day of administration, the tumor tissues of each group were excised and weighed, and the tumor growth rate of each group relative to the control (Reference Example 5) group was determined based on the formula below.The results in Table 1 are 11.
なお、上記ΔJ(験は3回に分けて行い、それぞれに対
照群を設けた。The above ΔJ test was conducted three times, and a control group was provided for each.
各群の平均腫瘍重量
腫瘍増殖率= X100対照群
の平均腫瘍重量
第1表
第1表から、実施例1の輸液が、参考例1〜5の翰f・
夜と較べて顕著なIl!r!瘍増殖1r(1制作用を示
すことが明らかに認められる。Average tumor weight of each group Tumor growth rate = X100 Average tumor weight of control group Table 1 From Table 1, it can be seen that the infusion of Example 1
Noticeable Il compared to night! r! It is clearly seen that tumor growth 1r (1r production) is observed.
なお、本発明アミノ酸輸液は、抗癌剤と(jf用するこ
とにより癌増殖抑制の相乗効果が期待できる。In addition, the amino acid infusion of the present invention can be expected to have a synergistic effect in inhibiting cancer growth when used with an anticancer drug (jf).
Claims (1)
も下記アミノ酸を下記の組成範囲内で含有することを特
徴とするアミノ酸輸液。 ―――――――――――――――――――――― アミノ酸 組成範囲 (g/全アミノ酸100g) ―――――――――――――――――――――― L−イソロイシン 5.25〜6.41 L−ロイシン 11.71〜14.31 L−リジン 8.24〜10.08 L−メチオニン 3.28〜 4.01 L−フェニルアラニン 8.76〜10.71 L−トレオニン 6.09〜 7.44 L−トリプトファン 1.22〜 1.49 L−アラニン 5.81〜 7.11 L−アルギニン 7.41〜 9.05 L−アスパラギン酸 3.56〜 4.35 L−システイン 0.93〜 1.14 L−グルタミン酸 6.08〜 7.44 L−ヒスチジン 6.14〜 7.50 L−プロリン 3.09〜 3.78 L−セリン 2.06〜 2.52 L−チロシン 0.33〜 0.40 アミノ酢酸 10.03〜12.25[Scope of Claims] An amino acid infusion that does not contain L-valine and is characterized by containing at least the following amino acids within the following composition range. ―――――――――――――――――――― Amino acid composition range (g/100g total amino acids) ―――――――――――――――――― --- L-isoleucine 5.25-6.41 L-leucine 11.71-14.31 L-lysine 8.24-10.08 L-methionine 3.28-4.01 L-phenylalanine 8.76 ~10.71 L-threonine 6.09-7.44 L-tryptophan 1.22-1.49 L-alanine 5.81-7.11 L-arginine 7.41-9.05 L-aspartic acid 3. 56-4.35 L-cysteine 0.93-1.14 L-glutamic acid 6.08-7.44 L-histidine 6.14-7.50 L-proline 3.09-3.78 L-serine 2. 06-2.52 L-tyrosine 0.33-0.40 Aminoacetic acid 10.03-12.25
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP27643285A JPS62135420A (en) | 1985-12-09 | 1985-12-09 | Amino acid transfusion solution |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP27643285A JPS62135420A (en) | 1985-12-09 | 1985-12-09 | Amino acid transfusion solution |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS62135420A true JPS62135420A (en) | 1987-06-18 |
Family
ID=17569334
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP27643285A Pending JPS62135420A (en) | 1985-12-09 | 1985-12-09 | Amino acid transfusion solution |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS62135420A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011125916A1 (en) * | 2010-04-07 | 2011-10-13 | 株式会社大塚製薬工場 | Composition for amelioration of hypoalbuminemia |
WO2016084850A1 (en) * | 2014-11-25 | 2016-06-02 | 国立大学法人 東京大学 | Composition for decreasing hematopoietic stem cells, and method for producing same |
WO2018025978A1 (en) * | 2016-08-05 | 2018-02-08 | 国立大学法人 東京大学 | Composition to be used for treating adult t cell leukemia/lymphoma and method for producing same |
-
1985
- 1985-12-09 JP JP27643285A patent/JPS62135420A/en active Pending
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011125916A1 (en) * | 2010-04-07 | 2011-10-13 | 株式会社大塚製薬工場 | Composition for amelioration of hypoalbuminemia |
JP5483775B2 (en) * | 2010-04-07 | 2014-05-07 | 株式会社大塚製薬工場 | Composition for improving hypoalbuminemia |
US9693982B2 (en) | 2010-04-07 | 2017-07-04 | Otsuka Pharmaceutical Factory, Inc. | Composition for amelioration of hypoalbuminemia |
WO2016084850A1 (en) * | 2014-11-25 | 2016-06-02 | 国立大学法人 東京大学 | Composition for decreasing hematopoietic stem cells, and method for producing same |
JPWO2016084850A1 (en) * | 2014-11-25 | 2017-08-31 | 国立大学法人 東京大学 | Composition for reducing hematopoietic stem cells and method for producing the same |
US10383836B2 (en) | 2014-11-25 | 2019-08-20 | The University Of Tokyo | Composition for decreasing hematopoietic stem cells, and method for producing same |
WO2018025978A1 (en) * | 2016-08-05 | 2018-02-08 | 国立大学法人 東京大学 | Composition to be used for treating adult t cell leukemia/lymphoma and method for producing same |
US11369580B2 (en) | 2016-08-05 | 2022-06-28 | The University Of Tokyo | Composition for treating adult T cell leukemia/lymphoma and method for producing same |
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