JPH05105633A - Glucose preparation and its production - Google Patents
Glucose preparation and its productionInfo
- Publication number
- JPH05105633A JPH05105633A JP3293646A JP29364691A JPH05105633A JP H05105633 A JPH05105633 A JP H05105633A JP 3293646 A JP3293646 A JP 3293646A JP 29364691 A JP29364691 A JP 29364691A JP H05105633 A JPH05105633 A JP H05105633A
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- JP
- Japan
- Prior art keywords
- glucose
- added
- cysh
- solution
- preparation
- 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.)
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Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、ブドウ糖製剤及びその
製造方法に関し、特に、ブドウ糖分解生成物である3−
デオキシグルコ−ソンを含有しないブドウ糖製剤及びそ
の製造方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a glucose preparation and a method for producing the same, and particularly to a glucose decomposition product 3-
TECHNICAL FIELD The present invention relates to a glucose preparation containing no deoxyglucosone and a method for producing the same.
【０００２】[0002]
【従来の技術】ブドウ糖製剤は、例えば、電解質液、そ
の他所望成分を配合した輸液（例えば、血液代用剤、高
カロリ−輸液等）として、又は、腹膜透析液として多用
されている。そして、現在市販の輸液には、1〜40％程
度のブドウ糖が配合されており、また、ブドウ糖注射液
として50％配合したものが市販されている。また、腹膜
透析液（以下ＰＤ液という。）には、通常、除水目的の
ため、1〜7％程度のブドウ糖が配合されている。［な
お、ＰＤ液の浸透圧調整剤として、ブドウ糖に代えて他
の物質を配合する製剤も開発されているが（特開平2−1
96724号公報等参照）、本発明は、ブドウ糖を浸透圧調
整剤として配合するＰＤ液などブドウ糖製剤を対象とす
るものである。］Glucose preparations are widely used, for example, as an infusion solution containing an electrolyte solution and other desired components (for example, blood substitute, high calorie infusion solution) or as a peritoneal dialysis solution. At present, commercially available infusion solutions contain about 1 to 40% glucose, and 50% glucose injection solutions are commercially available. Further, peritoneal dialysis fluid (hereinafter referred to as PD fluid) usually contains about 1 to 7% glucose for the purpose of removing water. [In addition, as an osmotic pressure adjusting agent for PD solution, a formulation in which another substance is mixed instead of glucose has been developed (Japanese Patent Laid-Open No. 2-1
The present invention is directed to glucose preparations such as PD solution containing glucose as an osmotic pressure adjusting agent. ]
【０００３】そして、輸液は、点滴液として静脈に直接
投与するものであり、また、ＰＤ液は、直接腹腔内に注
入するものであることから、いずれも無菌液とする必要
があり、その滅菌手段として、一般に、日本薬局方で規
定する加熱滅菌法（高圧蒸気滅菌法）が採用されてい
る。Since the infusion solution is directly administered to a vein as a drip solution, and the PD solution is directly injected into the abdominal cavity, it is necessary to make it aseptic solution. As a means, generally, a heat sterilization method (high-pressure steam sterilization method) specified by the Japanese Pharmacopoeia is adopted.
【０００４】ところで、ブドウ糖（グルコ−ス）は、加
熱滅菌工程及び長期間保存中に図１に示す分解経路に従
って分解し、種々の分解物が生成することが知られてお
り、一方、ブドウ糖は、ｐＨ3.0前後で最も安定である
ところから、ブドウ糖製剤の加熱滅菌時にｐＨを低く調
整するほうがブドウ糖の分解が少なく、安定であること
が知られている（「改訂・薬学領域の高カロリー輸液」
平岡栄一監修、1986年3月20日改訂、医薬ジャーナル社
発行、第99頁〜102頁参照）。Glucose is known to be decomposed according to the decomposition route shown in FIG. 1 during the heat sterilization process and long-term storage to produce various decomposed products. On the other hand, glucose is Since it is most stable at around pH 3.0, it is known that adjusting the pH to a low level during heat sterilization of glucose preparations results in less glucose decomposition and is more stable. "
Supervised by Eiichi Hiraoka, revised March 20, 1986, published by Pharmaceutical Journal, pp. 99-102).
【０００５】しかしながら、ＰＤ液は、腹膜と直接接触
するものであり、一方、生体ｐＨ値が7.4であるところ
から、ブドウ糖を配合したＰＤ液の加熱滅菌は、通常、
この生体ｐＨ値に近い4.5〜5.5の弱酸性側に調整して行
われており、また、輸液の加熱滅菌も同じく弱酸性側に
調整して行われている。そのため、市販の滅菌済輸液及
びＰＤ液中には、ブドウ糖の分解物が含まれており、こ
のブドウ糖の分解物は、血管透過性を亢進し、ＰＤ液に
あっては、除水能の低下、腹膜機能の低下の原因となる
と考えられている（「透析会誌」22(6)：p633〜637，19
89、「CAPD(3)0-45」第35回 日本透析療法学会総会 プ
ログラム、抄録集1990、p171 参照）。However, since the PD solution comes into direct contact with the peritoneum, and the biological pH value is 7.4, heat sterilization of the PD solution containing glucose is usually performed.
The pH is adjusted to a weak acidity of 4.5 to 5.5, which is close to the biological pH value, and the heat sterilization of the infusion solution is also adjusted to a weak acidity. Therefore, commercially available sterilized infusion solutions and PD solutions contain glucose decomposition products, and these glucose decomposition products enhance vascular permeability, and PD solutions have reduced water removal ability. , And is thought to cause a decrease in peritoneal function ("Dialysis Society of Japan" 22 (6): p633-637, 19).
89, “CAPD (3) 0-45” 35th Annual Meeting of the Japanese Society for Dialysis Therapy Program, Abstracts, 1990, p171).
【０００６】本発明者等は、後に詳記するとおり、ブド
ウ糖製剤におけるブドウ糖分解物、特に、加熱滅菌時に
おける分解物について鋭意研究を重ねた結果、この分解
物中の3−デオキシグルコ−ソンが、輸液にあっては、
静脈炎又は血栓性静脈炎の原因となり、また、ＰＤ液に
あっては、腹膜機能の低下の原因となる事実を発見し、
この発見に基づいて本発明を完成したものである。即
ち、本発明は、上記症例の原因となる3−デオキシグル
コ−ソン（ブドウ糖分解物）を含まないブドウ糖製剤及
びその製造方法を提供するにある。As will be described later in detail, the inventors of the present invention have conducted extensive studies on a glucose decomposition product in a glucose preparation, particularly a decomposition product during heat sterilization, and as a result, 3-deoxyglucosone in the decomposition product was , For infusion,
It was discovered that the cause of phlebitis or thrombophlebitis, and in the case of PD solution, the cause of deterioration of peritoneal function,
The present invention has been completed based on this discovery. That is, the present invention provides a glucose preparation that does not contain 3-deoxyglucosone (glucose degradation product) that causes the above cases, and a method for producing the same.
【０００７】[0007]
【課題を解決するための手段】そして、本発明は、上記
した3−デオキシグルコ−ソン（ブドウ糖分解生成物）
を含まないブドウ糖製剤を得る手段として、システイン
を添加し、加熱滅菌する点を特徴とするものであって、
本発明の要旨は、(1) ブドウ糖又はブドウ糖を含有する
配合剤にシステインを添加してなることを特徴とするブ
ドウ糖製剤、(2) ブドウ糖又はブドウ糖を含有する配合
剤にシステインを添加し、加熱滅菌することを特徴とす
るブドウ糖製剤の製造方法、である。The present invention also provides 3-deoxyglucosone (glucose decomposition product) as described above.
As a means for obtaining a glucose preparation containing no, cysteine is added, which is characterized in that it is sterilized by heating,
The gist of the present invention is (1) glucose preparation characterized in that cysteine is added to glucose or a compounding agent containing glucose, (2) cysteine is added to glucose or a compounding agent containing glucose, and heated. A method for producing a glucose preparation, which comprises sterilizing.
【０００８】以下、本発明を詳細に説明すると、本発明
者等は、輸液中に含まれているブドウ糖の分解生成物で
ある3−デオキシグルコ−ソン（以下3-ＤＧと略称す
る。）が投与部位に傷害を与えていることを見い出し
た。その概要について説明すると、本発明者等は、輸液
中のブドウ糖分解生成物が投与部位に悪影響を与えてい
るか否か、その作用と作用物質を検討するため、血管透
過性亢進作用の有無について実験した。用いた物質は、
ブドウ糖の代表的な分解物である3-ＤＧと5−ヒドロオ
キシメチルフルフラ−ル（以下5-ＨＭＦと略称する。）
について実験した。The present invention will be described in detail below. The present inventors have found that 3-deoxyglucosone (hereinafter abbreviated as 3-DG), which is a decomposition product of glucose contained in an infusion solution, is present. It was found that the administration site was injured. Explaining the outline, the present inventors have conducted an experiment on the presence or absence of a vascular permeability-enhancing effect in order to examine whether or not the glucose degradation product in the infusion has an adverse effect on the administration site and its action and active substance. did. The substances used are
3-DG and 5-hydroxymethylfurfural, which are typical degradation products of glucose (hereinafter abbreviated as 5-HMF).
Was experimented with.
【０００９】実験方法は、モルモットを用いた皮内反応
により行い、陰性対照として生理食塩液、陽性対照とし
てBradykinin（0.02％、0.01％）を用いた。その結果、
3-ＤＧに血管透過性亢進作用が認められ、しかも、持続
的な作用であった。他の5-ＨＭＦにはその作用が認めら
れず、また、ブドウ糖それ自身にもその作用が認められ
なかった。The experiment was carried out by an intradermal reaction using guinea pigs, using physiological saline as a negative control and Bradykinin (0.02%, 0.01%) as a positive control. as a result,
3-DG was found to have a vascular permeability-enhancing effect and was a persistent effect. The other 5-HMF did not show the action, and the glucose itself did not show the action.
【００１０】更に、本発明者等は、この度、ＰＤ液と腹
膜機能低下との関連について研究した結果、ＰＤ液に含
まれている高圧蒸気滅菌時の加熱により生じたブドウ糖
分解生成物のうち、3-ＤＧが腹膜の透過性亢進を引き起
こし、腹膜機能の低下を誘発することを見い出した。そ
の概要について説明すると、本発明者等は、まず、市販
のＰＤ溶液について、TLCにてこの糖分解物の同定を行
い、フルクト−ス（fructose）、5-ＨＭＦ、フルフラ−
ル（furfural）、グリオキサ−ル（glyoxal）及び3-Ｄ
Ｇが含有されていることを確認した。また、加熱滅菌時
に生じた分解物である3-ＤＧ及び5-ＨＭＦの定量を行っ
たところ、グルコ−ス濃度に依存してこれらの分解物の
増加が見られた。Furthermore, the present inventors have now studied the relationship between the PD solution and hypoperitoneal function, and as a result, of the glucose decomposition products produced by heating during high-pressure steam sterilization contained in the PD solution, It was found that 3-DG causes peritoneal hyperpermeability and induces a decline in peritoneal function. To explain the outline, the present inventors first identify the glycolysis product of TLC with respect to a commercially available PD solution, and then determine fructose, 5-HMF, and fructose.
Furfural, glyoxal and 3-D
It was confirmed that G was contained. In addition, when the amounts of 3-DG and 5-HMF, which are decomposition products generated during heat sterilization, were quantified, an increase in these decomposition products was observed depending on the glucose concentration.
【００１１】次に、糖分解物の腹膜機能に及ぼす影響に
ついて、ラットを用いて実験した。用いた検体は、
(1)：ろ過滅菌試料、(2)：(1)試料に3-ＤＧを添加した
試料、(3)：(1)試料に5-ＨＭＦを添加した試料及び
(4)：加熱滅菌（121℃、30分）した試料である。試験方
法として、これら(1)〜(4)の検体10ｍｌ／100ｇを腹腔
内に反復投与し、糖吸収率と尿素窒素のＤ／Ｐ比（排液
中濃度／血漿濃度）を調べた。Next, the effect of the glycolysis product on the peritoneal function was tested using rats. The sample used is
(1): Filter sterilized sample, (2): (1) sample added with 3-DG, (3): (1) sample added with 5-HMF, and
(4): Heat sterilized (121 ° C, 30 minutes) sample. As a test method, 10 ml / 100 g of these samples (1) to (4) were repeatedly administered intraperitoneally, and the sugar absorption rate and the D / P ratio of urea nitrogen (concentration in effluent / plasma concentration) were examined.
【００１２】その結果、加熱滅菌及び3-ＤＧ添加群は、
３週目でろ過滅菌試料群に比し排液中の糖濃度の低下が
見られ、尿素窒素のＤ／Ｐ比は、１週目にろ過滅菌試料
群に比し高値であった。5-ＨＭＦ添加群では、尿素窒素
Ｄ／Ｐの高値のみ認められた。これらの事実から、高圧
蒸気滅菌時に生じた3-ＤＧを主体とした糖分解物は、反
復投与により腹膜機能に影響を及ぼすことが明らかに示
唆された。As a result, the heat-sterilized and 3-DG added groups were
At the 3rd week, the sugar concentration in the effluent was found to be lower than that of the filter-sterilized sample group, and the D / P ratio of urea nitrogen was higher than that of the filter-sterilized sample group at the 1st week. In the 5-HMF-added group, only high values of urea nitrogen D / P were observed. From these facts, it was clearly suggested that the sugar degradation product mainly composed of 3-DG produced during autoclaving affected the peritoneal function by repeated administration.
【００１３】本発明者等は、以上詳記したとおり、輸液
については、それに含まれているブドウ糖の分解物のう
ち、3-ＤＧが投与部位に悪影響を与え、血管透過性亢進
作用を引き起こし、静脈炎や血栓性静脈炎の原因とな
り、また、ＰＤ液についても、それに含まれている3-Ｄ
Ｇの存在が腹膜機能低下の原因となる事実を発見した。
そして、輸液やＰＤ液には、高圧蒸気滅菌時に多量の3-
ＤＧの糖分解物が生成することから、本発明者等は、こ
の加熱滅菌時における3-ＤＧの生成を抑制することを技
術的課題として鋭意研究を重ねた結果、本発明を完成し
た。即ち、本発明は、加熱滅菌時にシステイン（以下Ｃ
ｙＳＨと略称する。）を添加することによって、3-ＤＧ
の生成が認められない輸液やＰＤ液などのブドウ糖製剤
を提供するものである。As described in detail above, regarding the infusion solution, the present inventors have found that among the glucose decomposition products contained therein, 3-DG adversely affects the administration site and causes a vascular permeability-enhancing action, 3-D, which causes phlebitis and thrombophlebitis, and also contains PD solution
We have discovered the fact that the presence of G causes hypoperitoneal dysfunction.
And, for infusion and PD solution, a large amount of 3-
Since a sugar decomposition product of DG is produced, the present inventors have completed the present invention as a result of intensive research conducted on the technical problem of suppressing the production of 3-DG during heat sterilization. That is, the present invention provides cysteine (hereinafter C
It is abbreviated as ySH. ) By adding 3-DG
It is intended to provide glucose preparations such as infusion solution and PD solution in which the production of lactic acid is not observed.
【００１４】ところで、ＣｙＳＨは、一般に、抗酸化剤
として知られている物質であり、これ以外に、トリプト
ファン、チロシン、ヒスチジン、メチオニン、グルタチ
オン、α−トコフェノ−ル、アスコルビン酸、リボフラ
ビン等が抗酸化剤として知られている。しかしながら、
本発明者等は、これら周知の抗酸化剤のうち、ＣｙＳＨ
を添加した場合、ブドウ糖製剤の加熱滅菌時に3-ＤＧ
（ブドウ糖分解物）の生成が認められず、その他の抗酸
化剤を添加すると、いずれも3-ＤＧが生成することを見
い出した（後記実験例参照）。この事実から、本発明に
おけるＣｙＳＨは、抗酸化作用に基づくものでないこと
が理解できる。By the way, CySH is a substance generally known as an antioxidant. In addition to this, tryptophan, tyrosine, histidine, methionine, glutathione, α-tocophenol, ascorbic acid, riboflavin and the like are antioxidants. Known as an agent. However,
The present inventors have found that among these known antioxidants, CySH
When added, 3-DG is added to the glucose preparation during heat sterilization.
No formation of (glucose degradation product) was observed, and it was found that when any other antioxidant was added, 3-DG was formed (see Experimental Example described later). From this fact, it can be understood that CySH in the present invention is not based on the antioxidant effect.
【００１５】本発明において、ＣｙＳＨの添加量は、ブ
ドウ糖配合量に対し0.7〜10％が好ましい。0.7％未満で
は、加熱滅菌時に3-ＤＧの生成がみられ、特に、ｐＨ6
以上で著しいので、好ましくなく、一方、10％を越えて
添加しても、ＣｙＳＨの生成抑制作用が顕著でない。本
発明では、上記添加範囲のうち、2〜10％がより好まし
く、更に、2〜7％、特に、5〜7％が最適である。また、
本発明では、弱酸性側でも、また、ｐＨ8の弱アルカリ
でも、好適に実施することができるが、ｐＨを2.5〜6に
調整した後加熱滅菌するのがより好ましく、これによっ
て、ブドウ糖の分解がより抑制される。In the present invention, the amount of CySH added is preferably 0.7 to 10% with respect to the amount of glucose blended. If it is less than 0.7%, 3-DG is produced during heat sterilization, especially at pH 6
Since the above is remarkable, it is not preferable. On the other hand, even if added over 10%, the effect of suppressing the production of CySH is not remarkable. In the present invention, the addition range is more preferably 2 to 10%, further preferably 2 to 7%, and most preferably 5 to 7%. Also,
In the present invention, it can be preferably carried out on a weakly acidic side and also on a weak alkali having a pH of 8, but it is more preferable to sterilize by heating after adjusting the pH to 2.5 to 6, whereby the decomposition of glucose is decomposed. More suppressed.
【００１６】ブドウ糖製剤の加熱滅菌時に電解質液が配
合されていると、従来より知られているとおり、この電
解質液がブドウ糖の分解を促進するので、本発明では、
ブドウ糖にＣｙＳＨを添加し、加熱滅菌した後電解質液
（滅菌済）を配合することもでき、これも本発明に包含
されるものである。更に、本発明で得られた3-ＤＧを含
まないブドウ糖製剤は、使用時に重炭酸ナトリウム等で
ｐＨを7.0〜7.5に調整して使用することができ、また、
アルカリ化剤として乳酸などを配合することができ、そ
の他所望成分を適宜配合することもでき、いずれも本発
明に包含されるものである。[0016] If an electrolyte solution is blended during heat sterilization of a glucose preparation, as is conventionally known, this electrolyte solution accelerates the decomposition of glucose. Therefore, in the present invention,
It is also possible to add CySH to glucose and heat sterilize it, and then add an electrolyte solution (sterilized), which is also included in the present invention. Further, the glucose preparation containing no 3-DG obtained in the present invention can be used by adjusting the pH to 7.0 to 7.5 with sodium bicarbonate or the like at the time of use.
Lactic acid and the like can be blended as an alkalizing agent, and other desired components can be blended appropriately, and all are included in the present invention.
【００１７】[0017]
【実施例】以下、本発明の実施例を比較例と共に挙げ、
本発明をより詳細に説明する。 （実施例１）検体組成として、132mEq／LのＮａ、3.5mE
q／LのＣａ、1.5mEq／LのＭｇ、102mEq／LのＣｌ、35mE
q／Lの乳酸及び1.5％ブドウ糖からなるブドウ糖・電解
質液配合剤（ＰＤ液）を準備し、この配合剤にＣｙＳＨ
を0.1％添加し、ｐＨを2〜8に調整した後、高圧蒸気滅
菌を行った。各配合剤の滅菌後の3-ＤＧ、5-ＨＭＦ、グ
ルコ−ス（Gluco）、フルクト−ス（Fruct）の各含量を
測定し、表１に示した。 （比較例１）比較のため、ＣｙＳＨを添加しない各配合
剤について、実施例１と同様高圧蒸気滅菌し、この滅菌
後の各含量を測定し、表１に併記した。EXAMPLES Examples of the present invention will be given below together with comparative examples.
The present invention will be described in more detail. (Example 1) As a sample composition, 132 mEq / L of Na and 3.5 mE
q / L Ca, 1.5mEq / L Mg, 102mEq / L Cl, 35mE
Prepare a glucose / electrolyte mixture (PD solution) consisting of q / L lactic acid and 1.5% glucose, and add CySH to this mixture.
0.1% was added to adjust the pH to 2 to 8, and then high-pressure steam sterilization was performed. Each content of 3-DG, 5-HMF, glucose (Gluco), and fructose (Fruct) after sterilization of each compounding agent was measured and shown in Table 1. (Comparative Example 1) For comparison, each compounding agent to which CySH was not added was subjected to high-pressure steam sterilization in the same manner as in Example 1, and each content after this sterilization was measured, and also shown in Table 1.
【００１８】[0018]
【表１】 [Table 1]
【００１９】表１から明らかなように、ＣｙＳＨを0.1
％添加した実施例１では、3-ＤＧの存在が認められず、
これに対して、ＣｙＳＨを添加しない比較例１では、3-
ＤＧが多量に含有していることが理解できる。そして、
実施例１の各滅菌済ブドウ糖・電解質液配合剤（ＰＤ
液）は、3-ＤＧが含まれていないため、腹膜機能の低下
がみられず、長期にわたって透析効果が維持できる製剤
が得られた。As is clear from Table 1, CySH is 0.1
%, The presence of 3-DG was not observed in Example 1
On the other hand, in Comparative Example 1 in which CySH was not added, 3-
It can be understood that DG is contained in a large amount. And
Each sterilized glucose / electrolyte solution mixture of Example 1 (PD
(Liquid) does not contain 3-DG, so that a decrease in peritoneal function was not observed, and a formulation capable of maintaining a dialysis effect for a long period of time was obtained.
【００２０】（実施例２）実施例１と同一検体組成を持
つＰＤ液にＣｙＳＨを0.01％、0.03％、0.10％（ブドウ
糖配合量に対し0.667％、2.0％、6.67％に相当）を添加
し、ｐＨを３及び６に調整した後、高圧蒸気滅菌し、得
られた滅菌済各ＰＤ液について、実施例１と同様各含量
を測定し、その測定結果を表２に示した。 （比較例２）比較のため、ＣｙＳＨを添加しない各ＰＤ
液について、滅菌後の各含量を表２に併記した。 （実験例）また、ＣｙＳＨ以外の抗酸化剤を添加し、滅
菌後の3-ＤＧの生成の有無について、次の実験を行なっ
た。実施例１と同一検体組成を持つＰＤ液にアスコルビ
ン酸、トリプトファン、ヒスチジン、メチオニンの各抗
酸化剤を0.1％（ブドウ糖配合量に対し6.67％に相当）
を添加し、実施例２と同様、ｐＨを３及び６に調整した
後、高圧蒸気滅菌し、得られた滅菌済各ＰＤ液につい
て、3-ＤＧの含量を測定し、その測定結果を表３に示し
た。(Example 2) CySH was added to PD solution having the same sample composition as in Example 1 with 0.01%, 0.03% and 0.10% of CySH (corresponding to 0.667%, 2.0% and 6.67% of glucose content). After adjusting the pH to 3 and 6, high-pressure steam sterilization was performed, and each content of the obtained sterilized PD solutions was measured in the same manner as in Example 1, and the measurement results are shown in Table 2. (Comparative Example 2) For comparison, each PD without addition of CySH
Each content of the liquid after sterilization is also shown in Table 2. (Experimental example) Further, an antioxidant other than CySH was added, and the following experiment was conducted for the presence / absence of generation of 3-DG after sterilization. 0.1% of each antioxidant of ascorbic acid, tryptophan, histidine, and methionine was added to PD solution having the same sample composition as in Example 1 (equivalent to 6.67% of glucose content).
Was added and the pH was adjusted to 3 and 6 in the same manner as in Example 2, and then high pressure steam sterilization was performed, and the content of 3-DG was measured for each sterilized PD solution obtained, and the measurement results are shown in Table 3. It was shown to.
【００２１】[0021]
【表２】 [Table 2]
【表３】 [Table 3]
【００２２】表２から明らかなように、ＣｙＳＨをブド
ウ糖配合量に対し2.0％以上、特に6％以上添加すること
により、より一層3-ＤＧの分解物が生成しないことが理
解できる。また、表３から明らかなように、他の抗酸化
剤（アスコルビン酸、トリプトファン、ヒスチジン、メ
チオニンの各抗酸化剤）を添加しても、その滅菌後のＰ
Ｄ液中に3-ＤＧを含むものであり、これを表２に示す同
一条件のＣｙＳＨ（0.1％添加量、ｐＨ６）の場合と比
較すると、両者間に明白な差が認められる。この事実か
ら、本発明におけるＣｙＳＨは、抗酸化作用に基づくも
のでなく、それ以外の作用に基づくものであることが理
解できる。As is clear from Table 2, it can be understood that by adding 2.0% or more, especially 6% or more of CySH to the glucose blending amount, the decomposition product of 3-DG is not further generated. Further, as is clear from Table 3, even if other antioxidants (ascorbic acid, tryptophan, histidine, and methionine antioxidants) were added, P after sterilization
Solution D contains 3-DG, and when this is compared with the case of CySH (0.1% addition amount, pH 6) under the same conditions shown in Table 2, a clear difference is observed between the two. From this fact, it can be understood that the CySH in the present invention is not based on the antioxidant effect but based on the other effects.
【００２３】（実施例３）検体組成として、40mEq／Lの
Ｎａ、35mEq／LのＫ、40mEq／LのＣｌ、8mMのＰｉ、20m
Eq／Lの乳酸及び10％ブドウ糖からなるブドウ糖・電解
質液配合剤を準備した。この配合剤にＣｙＳＨを1％添
加し、ｐＨを2〜8に調整した後、高圧蒸気滅菌し、得ら
れた滅菌済各配合剤について、実施例１と同様各含量を
測定し、その測定結果を表４に示した。 （比較例３）また、比較のため、ＣｙＳＨを添加しない
各配合剤について、滅菌後の各含量を表４に併記した。(Example 3) As a sample composition, 40mEq / L Na, 35mEq / L K, 40mEq / L Cl, 8mM Pi, 20m
A glucose / electrolyte mixture formulation consisting of Eq / L lactic acid and 10% glucose was prepared. CySH was added to this compounding agent in an amount of 1%, the pH was adjusted to 2 to 8, and high-pressure steam sterilization was performed. For each sterilized compounding agent obtained, the content was measured in the same manner as in Example 1, and the measurement results were obtained. Is shown in Table 4. (Comparative Example 3) For comparison, Table 4 also shows the respective contents after sterilization of each compounding agent to which CySH was not added.
【００２４】[0024]
【表４】 [Table 4]
【００２５】表４から明らかなように、ＣｙＳＨを1％
添加した実施例３では、3-ＤＧの存在が認められず、こ
れに対して、ＣｙＳＨを添加しない比較例３では、3-Ｄ
Ｇが多量に含有していることが理解できる。As is clear from Table 4, CySH is 1%
In the added Example 3, the presence of 3-DG was not recognized, whereas in Comparative Example 3 in which CySH was not added, 3-D was added.
It can be understood that G is contained in a large amount.
【００２６】（実施例４）検体組成として、35mEq／Lの
Ｎａ、20mEq／LのＫ、35mEq／LのＣｌ、20mEq／Lの乳酸
及び15％ブドウ糖からなるブドウ糖・電解質液配合剤を
準備した。この配合剤にＣｙＳＨを1.5％添加し、ｐＨ
を6.0に調整した後、高圧蒸気滅菌し、得られた滅菌済
各配合剤について、実施例１と同様各含量を測定し、そ
の測定結果を表５に示した。 （比較例４）また、比較のため、ＣｙＳＨを添加しない
配合剤について、滅菌後の各含量を表５に併記した。(Example 4) As a sample composition, a glucose / electrolyte liquid mixture containing 35 mEq / L Na, 20 mEq / L K, 35 mEq / L Cl, 20 mEq / L lactic acid and 15% glucose was prepared. .. CySH was added to this compounding agent by 1.5%, and the pH was adjusted.
Was adjusted to 6.0 and then sterilized by high pressure steam, and the content of each sterilized compounding agent obtained was measured in the same manner as in Example 1, and the measurement results are shown in Table 5. (Comparative Example 4) For comparison, Table 5 also shows the respective contents after sterilization of the compounding agent to which CySH was not added.
【００２７】[0027]
【表５】 [Table 5]
【００２８】表５から明らかなように、ＣｙＳＨを1.5
％添加した実施例４では、3-ＤＧの存在が認められず、
これに対して、ＣｙＳＨを添加しない比較例４では、3-
ＤＧが多量に含有していることが理解できる。As is clear from Table 5, CySH is 1.5
%, In Example 4, the presence of 3-DG was not recognized,
On the other hand, in Comparative Example 4 in which CySH was not added, 3-
It can be understood that DG is contained in a large amount.
【００２９】次に、表６に示す各検体（実施例４の上記
検体組成からなるもの）を末梢静脈に投与し、静脈炎発
症への影響を調べた。試験動物として各群３匹づつのウ
サギを用い、耳介静脈にステンレスの針を用いて50ｍｌ
／ｋｇ／日を毎日６時間かけて投与し、５日間反復し
た。投与期間中、投与後に注入部位から１ｃｍ離れた部
位の観察を行なった。その結果を表６に示した。Next, each sample shown in Table 6 (having the above sample composition of Example 4) was administered to a peripheral vein, and the influence on the development of phlebitis was examined. As test animals, 3 rabbits in each group were used, and 50 ml was added to the ear vein using a stainless needle.
/ Kg / day was administered daily for 6 hours and repeated for 5 days. During the administration period, a site 1 cm away from the injection site was observed after the administration. The results are shown in Table 6.
【００３０】[0030]
【表６】 [Table 6]
【００３１】表６から明らかなように、ＣｙＳＨを1.5
％添加した滅菌検体（実施例４に相当するもの）では、
１日経過後で平均点が0.16であり、５日経過後0.66であ
るのに対し、ＣｙＳＨを添加しない滅菌検体（比較例４
に相当するもの）では、１日経過後0.5であり、５日経
過後1.33であり、この事実から、高圧蒸気滅菌時におけ
るＣｙＳＨ添加の有無、即ち、ブドウ糖の分解物である
3-ＤＧの有無により、静脈炎発症への影響に差が生ずる
ことが理解できる。As is clear from Table 6, CySH is 1.5
% Of the sterilized sample (corresponding to Example 4),
The average point was 0.16 after 1 day and was 0.66 after 5 days, whereas the sterilized sample without addition of CySH (Comparative Example 4
Is equivalent to 0.5) after 1 day and 1.33 after 5 days. From this fact, it is the presence or absence of addition of CySH during high-pressure steam sterilization, that is, the decomposition product of glucose.
It can be understood that the presence or absence of 3-DG makes a difference in the effect on the development of phlebitis.
【００３２】（実施例５）検体組成として、ブドウ糖1
％、5％、10％、30％及び50％水溶液を準備し、各水溶
液にＣｙＳＨを0.1％、0.5％、1.0％、3.0％及び5.0％
をそれぞれ添加し、ｐＨを6.0に調整した後、高圧蒸気
滅菌した。各水溶液の滅菌後の3-ＤＧ、グルコ−ス（Gl
uco）、フルクト−ス（Fruct）の各含量を測定し、表７
に示した。 （比較例５）比較のため、ＣｙＳＨを添加しない各ブド
ウ糖水溶液について、実施例５と同様高圧蒸気滅菌し、
この滅菌後の各含量を測定し、表７に併記した。Example 5 As a sample composition, glucose 1
%, 5%, 10%, 30% and 50% aqueous solutions are prepared, and CySH is added to each aqueous solution at 0.1%, 0.5%, 1.0%, 3.0% and 5.0%.
Was added to adjust the pH to 6.0, and then autoclaved. 3-DG and glucose (Gl) after sterilization of each aqueous solution
uco) and fructose (Fruct) were measured and the results are shown in Table 7.
It was shown to. (Comparative Example 5) For comparison, each glucose aqueous solution to which CySH was not added was subjected to high-pressure steam sterilization in the same manner as in Example 5,
Each content after this sterilization was measured and is also shown in Table 7.
【００３３】[0033]
【表７】 [Table 7]
【００３４】表７から明らかなように、ブドウ糖の各％
水溶液は、ＣｙＳＨを0.1〜5％添加した場合、3-ＤＧの
分解物が認められず、ＣｙＳＨを添加しない場合には、
多量の3-ＤＧが認められた。As is clear from Table 7, each% of glucose
When 0.1 to 5% of CySH was added to the aqueous solution, 3-DG decomposition products were not observed, and when CySH was not added,
A large amount of 3-DG was observed.
【００３５】[0035]
【発明の効果】本発明は、以上詳記したとおり、ブドウ
糖又はブドウ糖を含有する配合剤にＣｙＳＨを添加し、
加熱滅菌する点を特徴とし、このＣｙＳＨの添加によ
り、3-ＤＧ（分解物）を含まないブドウ糖製剤が得られ
る効果が生ずる。そして、本発明により、輸液にあって
は、静脈炎や血栓性静脈炎を呈しない製剤を提供するこ
とができ、また、腹膜透析液用製剤にあっては、透析効
果が長期にわたり維持できる製剤を提供することができ
る。As described in detail above, the present invention comprises adding CySH to glucose or a compounding agent containing glucose,
Characterized by heat sterilization, the addition of this CySH has the effect of obtaining a glucose preparation containing no 3-DG (degradation product). Further, according to the present invention, in the case of infusion, it is possible to provide a preparation which does not exhibit phlebitis or thrombophlebitis, and in the case of a peritoneal dialysis solution preparation, a dialysis effect which can be maintained for a long period of time. Can be provided.
【図１】グルコ−スの分解経路を示す図である。FIG. 1 is a diagram showing a glucose degradation pathway.
Claims (4)
にシステインを添加してなることを特徴とするブドウ糖
製剤。1. A glucose preparation comprising cysteine added to glucose or a compounding agent containing glucose.
にシステインを添加し、加熱滅菌することを特徴とする
ブドウ糖製剤の製造方法。2. A method for producing a glucose preparation, which comprises adding cysteine to glucose or a compounding agent containing glucose and performing heat sterilization.
対し0.7〜10％である請求項１又は請求項２に記載のブ
ドウ糖製剤又はその製造方法。3. The glucose preparation according to claim 1 or 2, or the method for producing the same, wherein the amount of cysteine added is 0.7 to 10% of the glucose content.
に、ブドウ糖配合量に対し0.7〜10％のシステインを添
加し、ｐＨを2〜8に調整した後、高圧蒸気滅菌すること
を特徴とするブドウ糖製剤の製造方法。4. Glucose characterized in that 0.7-10% cysteine is added to glucose or a compounding agent containing glucose to adjust the pH to 2-8, and then high-pressure steam sterilization is performed. Manufacturing method of pharmaceuticals.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3293646A JPH05105633A (en) | 1991-10-14 | 1991-10-14 | Glucose preparation and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3293646A JPH05105633A (en) | 1991-10-14 | 1991-10-14 | Glucose preparation and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH05105633A true JPH05105633A (en) | 1993-04-27 |
Family
ID=17797410
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3293646A Pending JPH05105633A (en) | 1991-10-14 | 1991-10-14 | Glucose preparation and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH05105633A (en) |
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