JPS6254776B2 - - Google Patents
Info
- Publication number
- JPS6254776B2 JPS6254776B2 JP58165129A JP16512983A JPS6254776B2 JP S6254776 B2 JPS6254776 B2 JP S6254776B2 JP 58165129 A JP58165129 A JP 58165129A JP 16512983 A JP16512983 A JP 16512983A JP S6254776 B2 JPS6254776 B2 JP S6254776B2
- Authority
- JP
- Japan
- Prior art keywords
- albumin
- hma
- hna
- bond
- less
- 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.)
- Expired
Links
- 108010088751 Albumins Proteins 0.000 claims description 36
- 102000009027 Albumins Human genes 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 238000000034 method Methods 0.000 description 15
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 9
- 229960003067 cystine Drugs 0.000 description 9
- 238000000502 dialysis Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 108010053070 Glutathione Disulfide Proteins 0.000 description 4
- 108010071390 Serum Albumin Proteins 0.000 description 4
- 102000007562 Serum Albumin Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000005194 fractionation Methods 0.000 description 4
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 108010004546 mercaptoalbumin Proteins 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- DZTHIGRZJZPRDV-LBPRGKRZSA-N N-acetyl-L-tryptophan Chemical compound C1=CC=C2C(C[C@H](NC(=O)C)C(O)=O)=CNC2=C1 DZTHIGRZJZPRDV-LBPRGKRZSA-N 0.000 description 1
- DZTHIGRZJZPRDV-UHFFFAOYSA-N Nalpha-Acetyltryptophan Natural products C1=CC=C2C(CC(NC(=O)C)C(O)=O)=CNC2=C1 DZTHIGRZJZPRDV-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000002016 colloidosmotic effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940116191 n-acetyltryptophan Drugs 0.000 description 1
- 108010059904 nonmercaptalbumin Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229960005480 sodium caprylate Drugs 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
【発明の詳細な説明】
本発明は、アルブミン製剤の製造方法に関す
る。さらに詳しくは、−Ｓ−Ｓ−結合を有する分
子量10000以下の化合物の少なくとも一部を除去
する工程を含むことを特徴とするアルブミン製剤
の製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing an albumin preparation. More specifically, the present invention relates to a method for producing an albumin preparation, which includes a step of removing at least a portion of a compound having a -S-S- bond and a molecular weight of 10,000 or less.
最近、血液の有効利用と輸血による副作用の防
止の両面から、全血をそのまま保存血液として使
用するのではなく、できるだけ細かい成分に分け
て患者にとつて必要な成分のみを輸注し、他の成
分はそれを必要とする別の患者に役立てようとい
う方式、すなわち、成分製剤としての利用が急増
してきた。 Recently, in order to effectively utilize blood and prevent side effects from blood transfusions, instead of using whole blood as stored blood, we have begun to divide it into as small a component as possible and infuse only the components that are necessary for the patient, while other components are being transfused. There has been a rapid increase in the use of drugs to help other patients who need them, that is, as ingredient preparations.
アルブミン製剤は最も広く用いられている成分
製剤の一つで、厚生省薬務局の生物学的製剤基準
潤によれば、「加熱人血漿蛋白」と「人血清アル
ブミン」とがあり、浮腫、腹水の防止に、また、
出血性シヨツクや火傷の救急治療、さらには血漿
交換時の輸液として有用である。 Albumin preparations are one of the most widely used ingredient preparations, and according to the Biological Products Standards of the Pharmaceutical Affairs Bureau of the Ministry of Health, Labor and Welfare, they include ``heated human plasma protein'' and ``human serum albumin,'' which can cause edema and ascites. In addition, to prevent
It is useful for emergency treatment of bleeding shots and burns, and as an infusion during plasma exchange.
アルブミンは血漿膠質浸透圧の保持、Ca〓、
Cu〓、Zn〓、ビリルビン等の輸送、または予備
アミノ酸として生体内で重要な役割を果たしてい
る。 Albumin maintains plasma colloid osmotic pressure, Ca〓,
It plays an important role in the body, transporting Cu〓, Zn〓, bilirubin, etc., or as a reserve amino acid.
また、人血漿アルブミンは、通常メルカプトア
ルブミン（HMA）とノンメルカプトアルブミン
（HNA）より成ることも知られている。ここで言
うHMAとは、第34番目のアミノ酸がシステイン
である人アルブミンであり、HNAとは、このシ
ステインとシスチン、酸化型グルタチオン、また
はその他の−Ｓ−Ｓ−結合を有する低分子化合物
が、分子間SH、−Ｓ−Ｓ−交換反応により結合し
たものを言う。 It is also known that human plasma albumin usually consists of mercaptoalbumin (HMA) and non-mercaptoalbumin (HNA). HMA here refers to human albumin in which the 34th amino acid is cysteine, and HNA refers to cysteine, cystine, oxidized glutathione, or other low-molecular compounds having -S-S- bonds. Refers to bonds bonded by intermolecular SH, -S-S- exchange reactions.
ここで、全アルブミンに占めるHMAの割合を
示すため、ＰHMAなる値を定義する。 Here, a value of PHMA is defined to indicate the proportion of HMA in total albumin.
ＰHMA＝ＱＨＭＡ／ＱＨＭＡ＋ＱＨＮＡ×100（％）
ただし、ＱHMA、ＱHNAは、それぞれHMA、
HNAの量を表わす。 P HMA =Q HMA /Q HMA +Q HNA ×100 (%) However, Q HMA and Q HNA are HMA and Q HNA, respectively.
Represents the amount of HNA.
本発明者らの研究によれば、腎臓や肝臓の疾患
者をはじめ種々の疾患者の血漿アルブミンは、健
常人のそれと比較してＰHMAが低い。したがつ
て、これらの疾患者の治療には、ＰHMAの高いア
ルブミン製剤を用いることが望ましい。ところ
が、従来から市販されているアルブミン製剤中の
アルブミンは、健常人血清中のそれと比べてＰHM
Ａが低く、アルブミン製剤として好ましい組成と
は言えない。さらには、−Ｓ−Ｓ−結合を有する
低分子物質の存在下では、HMA→HNAの変化が
起こり易いことも判明した。 According to research conducted by the present inventors, plasma albumin of patients with various diseases including those with kidney and liver diseases has a lower P HMA than that of healthy individuals. Therefore, it is desirable to use albumin preparations with high P HMA in the treatment of patients with these diseases. However, albumin in commercially available albumin preparations has a lower PHM than that in the serum of healthy individuals.
A is low, and the composition cannot be said to be preferable as an albumin preparation. Furthermore, it was also found that the change from HMA to HNA is likely to occur in the presence of a low-molecular substance having a -S-S- bond.
コーンの冷エタノール分画法をはじめとする、
従来のアルブミン製剤の製造法においては、ＰHM
Ａに及ぼす共存物質の影響についてまつたく着目
されていないため、製造工程中にHMAの少なく
とも一部がHNAに変化して、ＰHMAの高いアルブ
ミン製剤が得られなかつたり、製品完成後、保存
中にＰHMAが低下するという欠点があつた。 Including Cohn's cold ethanol fractionation method,
In the conventional production method of albumin preparations, P HM
Because not much attention has been paid to the effects of coexisting substances on A , at least a portion of HMA may change to HNA during the manufacturing process, making it impossible to obtain albumin preparations with high P HMA , or causing problems during storage after the product is completed. However, the disadvantage was that the P HMA decreased.
そこで、本発明者らは、従来技術の問題点を克
服すべく鋭意研究の結果、製造工程中にＰHMAが
著しく変化せず、かつその値が高く安定なアルブ
ミン製剤の製造法を見い出し、本発明を完成する
に到つた。 Therefore, as a result of intensive research to overcome the problems of the conventional technology, the present inventors discovered a method for producing a stable albumin preparation that does not significantly change P HMA during the production process and has a high value. He has completed his invention.
すなわち、本発明は、−Ｓ−Ｓ−結合を持つ分
子量10000以下の化合物をアルブミンに対して
5mol％以下にする工程を有することを特徴とす
るアルブミン製剤の製造方法である。 That is, the present invention provides a compound having a -S-S- bond with a molecular weight of 10,000 or less for albumin.
This is a method for producing an albumin preparation, comprising a step of reducing the concentration to 5 mol% or less.
本発明において、アルブミン製剤を製造するた
めに行なう人血漿分画方法は、一般に用いられる
方法、例えばコーンの冷エタノール分画法等でよ
く、特に限定されるものではない。 In the present invention, the human plasma fractionation method used to produce the albumin preparation may be any commonly used method, such as Cohn's cold ethanol fractionation method, and is not particularly limited.
ここで言う−Ｓ−Ｓ−結合を持つ分子量10000
以下の化合物は、下記の構造式で示されるシスチ
ン、酸化型グルタチオン等が考えられるが、特に
限定されるものではない。 Here, the molecular weight with -S-S- bond is 10,000
The following compounds may include cystine, oxidized glutathione, etc. represented by the following structural formula, but are not particularly limited.
−Ｓ−Ｓ−結合を持つ分子量10000以下の化合
物は、アルブミンに対して5mol％以下にするこ
とが好ましく、そうすることによつてその後の製
造工程でＰHMAがほとんど変化せず、かつその値
の高い製剤が得られる。また、このようにして得
られた製剤のＰHMAは安定であり、保存によつて
も変化しない。−Ｓ−Ｓ−結合を持つ分子量10000
以下の化合物は、実用上はアルブミンに対して
3mol％以下にすることが好ましく、できれば
1mol％以下にすることが望ましい。 The compound with a -S-S- bond and a molecular weight of 10,000 or less is preferably 5 mol% or less based on albumin, so that the P HMA hardly changes in the subsequent manufacturing process and its value A formulation with high Furthermore, the P HMA of the thus obtained formulation is stable and does not change even upon storage. -S-S- bond with molecular weight 10000
The following compounds are practically used for albumin.
It is preferable to keep it below 3 mol%, preferably
It is desirable to keep it below 1 mol%.
−Ｓ−Ｓ−結合を持つ分子量10000以下の化合
物をアルブミンに対して5mol％以下にする方法
は、アルブミンと、シスチンおよび酸化型グルタ
チオンを分離できる方法であれば特に限定され
ず、分別沈殿法、クロマトグラフイー法、過
法、透析法等を用いることができる。ただし、最
も広く用いられている分別沈殿法は、アルブミン
の回収率が低く、分離効率、経済性、操作性の点
から、通常は透析法が好ましい。−Ｓ−Ｓ−結合
を持つ分子量10000以下の化合物の除去操作は、
アルブミン製剤を製造する工程のなるべく初期に
行なう方がよく、少なくとも加熱処理操作の前に
は終えているのが好ましい。 The method of reducing the compound having a molecular weight of 10,000 or less with a -S-S- bond to 5 mol% or less of albumin is not particularly limited as long as it can separate albumin from cystine and oxidized glutathione, such as fractional precipitation, A chromatography method, a filtration method, a dialysis method, etc. can be used. However, the most widely used fractional precipitation method has a low albumin recovery rate, and dialysis is usually preferred from the standpoints of separation efficiency, economy, and operability. The removal operation for compounds with a molecular weight of 10,000 or less that has -S-S- bonds is as follows:
It is preferable to carry out this process as early as possible in the process of producing an albumin preparation, and it is preferable to complete it at least before the heat treatment operation.
総アルブミンの分析には、色素結合性、電気泳
動法、免疫学的方法、各種クロマトグラフイー法
等を用いることができる。 For analysis of total albumin, dye binding, electrophoresis, immunological methods, various chromatography methods, etc. can be used.
またHMA、HNAの分析法は、両者を分離定量
できる方法ならば特に限定されないが、特願昭57
−177505号に示された方法を利用するのが好まし
く、総アルブミンの分析にもこれを使用すること
ができる。 The analytical method for HMA and HNA is not particularly limited as long as it can separate and quantify both.
Preferably, the method described in No. 177505 is utilized and can also be used for the analysis of total albumin.
一方、−Ｓ−Ｓ−結合を持つ分子量10000以下の
化合物の分析法は、−Ｓ−Ｓ−結合を還元しチオ
ールとして検出する方法等が考えられるが、例え
ばシスチンおよび酸化型グルタチオンの分析に
は、アミノ酸分析計を用いるのが好ましい。 On the other hand, for the analysis of compounds with a molecular weight of 10,000 or less that have an -S-S- bond, methods such as reducing the -S-S- bond and detecting it as a thiol can be considered, but for example, for the analysis of cystine and oxidized glutathione, It is preferable to use an amino acid analyzer.
以上説明したように、本発明によれば、製造工
程中にＰHMAが低下することなく、かつその値の
高いアルブミン製剤を製造することができる。そ
して、本発明の最大の効果は、この製剤中に−Ｓ
−Ｓ−結合を持つ低分子化合物がほとんど含まれ
ないため、保存中にＰHMAが低下しないことであ
る。 As explained above, according to the present invention, an albumin preparation with a high P HMA value can be produced without decreasing the P HMA value during the production process. The greatest effect of the present invention is that -S
Since it contains almost no low-molecular-weight compounds with -S- bonds, PHMA does not decrease during storage.
腎臓疾患者や肝臓疾患者等の血漿アルブミン
は、一般にＰHMAが低く、これらの疾患者の治療
には、従来のＰHMAの低いアルブミン製剤はふさ
わしくない。本発明によれば、これらの疾患者の
治療に好ましいＰHMAが高く、安定なアルブミン
製剤を効率よく製造することができる。 Plasma albumin of patients with kidney disease, liver disease, etc. generally has low P HMA , and conventional albumin preparations with low P HMA are not suitable for the treatment of these patients. According to the present invention, it is possible to efficiently produce a stable albumin preparation with high P HMA , which is preferable for the treatment of patients with these diseases.
以下に本発明の実施例を示すが、本発明は、こ
れら実施例の範囲に限定されるものではない。 Examples of the present invention are shown below, but the present invention is not limited to the scope of these Examples.
実施例 １
ＰHMAが73％である新鮮な健常人血清より、コ
ーンの冷エタノール分画法に基きフラクシヨン
−４の上清を得た。前処理をして含硫化合物を除
去したセロフアン膜を用いて、先の上清20mlを透
析し、シスチンをはじめとする低分子化合物を除
去した。使用した透析液は、0.08MNaCl＋イオン
強度0.02のリン酸ナトリウム緩衝液（PH7.54）２
であり、これを途中３回交換し、計３日間透析
した。透析後のアルブミン溶液からは、シスチン
は検出されなかつた。次に、このアルブミン溶液
にカプリル酸ナトリウムとＮ−アセチルトリプト
フアンを加え、60℃で10時間加熱処理した。加熱
処理後のＰHMAは69％で、さほど大きな低下は見
られなかつた。Example 1 Fraction-4 supernatant was obtained from fresh healthy human serum containing 73% P HMA based on Cohn's cold ethanol fractionation method. Using a cellophane membrane that had been pretreated to remove sulfur-containing compounds, 20 ml of the supernatant was dialyzed to remove low-molecular-weight compounds such as cystine. The dialysate used was 0.08M NaCl + sodium phosphate buffer (PH7.54) with an ionic strength of 0.02.
This was exchanged three times during the course of dialysis for a total of three days. No cystine was detected in the albumin solution after dialysis. Next, sodium caprylate and N-acetyltryptophan were added to this albumin solution, and the mixture was heat-treated at 60°C for 10 hours. The P HMA after heat treatment was 69%, and no significant decrease was observed.
測定方法
ＰHMA測定は以下に示すような条件の液体クロ
マトグラフイーで行なつた。 Measurement method P HMA measurement was performed using liquid chromatography under the conditions shown below.
カラム：旭化成工業(株)商品名Asahipak GS−520
内径7.5mm、長さ50cm×４本
溶離液：0.1Mリン酸ナトリウム＋0.3M塩化ナト
リウム（PH7.0）
ポンプ：日本分光工業(株)商品名Twincle（流量：
0.5ml／min）
検出器：日本分光工業(株)商品名UVIDEC（波長：
280nｍ）
得られた第１図のクロマトグラムのＡ（メルカ
プトアルブミン）とＢ（ノンメルカプトアルブミ
ン）の面積をそれぞれＱHMA、ＱHNAとしてＰHMA
を算出した。Column: Asahi Kasei Industries, Ltd. Product name: Asahipak GS-520
Inner diameter 7.5 mm, length 50 cm x 4 bottles Eluent: 0.1M sodium phosphate + 0.3M sodium chloride (PH7.0) Pump: JASCO Corporation, trade name Twincle (flow rate:
0.5ml/min) Detector: JASCO Corporation, trade name UVIDEC (wavelength:
280nm) The areas of A (mercaptalbumin) and B (non-mercaptalbumin) in the obtained chromatogram in Figure 1 are defined as Q HMA and Q HNA , respectively, as P HMA
was calculated.
比較例 １
実施例１で示した透析前のアルブミン溶液のシ
スチン含量は２mg／dlであり、アルブミンに対し
て16mol％であつたが、これを透析せずシスチン
共存のままで熱処理すると、ＰHMAは57％まで低
下した。得られたアルブミン溶液について、実施
例１と同様にしてクロマトグラムをを第２図に示
した。Comparative Example 1 The cystine content of the albumin solution before dialysis shown in Example 1 was 2 mg/dl, which was 16 mol% with respect to albumin, but when it was heat-treated in the presence of cystine without dialysis, P HMA decreased to 57%. A chromatogram of the albumin solution obtained in the same manner as in Example 1 is shown in FIG.
実施例 ２
実施例１で透析後、熱処理したアルブミン製剤
を３℃で30日間保存しても、ＰHMAの変化はなか
つた。Example 2 Even when the heat-treated albumin preparation after dialysis in Example 1 was stored at 3° C. for 30 days, there was no change in P HMA .
比較例 ２
シスチン濃度２mg／dlのフラクシヨン−４の
上清を透析処理せず、３℃で30日間保存すると、
ＰHMAは74％から58％まで低下した。Comparative Example 2 When the supernatant of Fraction-4 with a cystine concentration of 2 mg/dl was stored at 3°C for 30 days without dialysis treatment,
P HMA decreased from 74% to 58%.
第１図は実施例１で得られたアルブミン製剤を
液体クロマトグラフイーで分析して得られたクロ
マトグラムの１例、第２図は比較例１で得られた
アルブミン溶液を同様に分析して得られたクロマ
トグラムである。
Figure 1 shows an example of a chromatogram obtained by analyzing the albumin preparation obtained in Example 1 using liquid chromatography, and Figure 2 shows an example of a chromatogram obtained by analyzing the albumin solution obtained in Comparative Example 1 in the same manner. This is the obtained chromatogram.
Claims (1)
るに際して、−Ｓ−Ｓ−結合をもつ分子量10000以
下の化合物をアルブミンに対して5mol％以下に
する工程を有することを特徴とするアルブミン製
剤の製造方法。1. A method for producing an albumin preparation by fractionating human plasma, which comprises the step of reducing the amount of a compound having a -S-S- bond and a molecular weight of 10,000 or less to 5 mol% or less of albumin. .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58165129A JPS6056926A (en) | 1983-09-09 | 1983-09-09 | Production of albumin preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58165129A JPS6056926A (en) | 1983-09-09 | 1983-09-09 | Production of albumin preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6056926A JPS6056926A (en) | 1985-04-02 |
| JPS6254776B2 true JPS6254776B2 (en) | 1987-11-17 |
Family
ID=15806452
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58165129A Granted JPS6056926A (en) | 1983-09-09 | 1983-09-09 | Production of albumin preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6056926A (en) |
-
1983
- 1983-09-09 JP JP58165129A patent/JPS6056926A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6056926A (en) | 1985-04-02 |
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