CS239838B1 - Processing of humen imunoglobuline - Google Patents
Processing of humen imunoglobuline Download PDFInfo
- Publication number
- CS239838B1 CS239838B1 CS844767A CS476784A CS239838B1 CS 239838 B1 CS239838 B1 CS 239838B1 CS 844767 A CS844767 A CS 844767A CS 476784 A CS476784 A CS 476784A CS 239838 B1 CS239838 B1 CS 239838B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- maltose
- immunoglobulins
- dialysis
- pepsin
- intravenous administration
- Prior art date
Links
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract description 24
- 102000018358 immunoglobulin Human genes 0.000 claims abstract description 24
- 229940072221 immunoglobulins Drugs 0.000 claims abstract description 18
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims abstract description 13
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 9
- 102000057297 Pepsin A Human genes 0.000 claims abstract description 8
- 108090000284 Pepsin A Proteins 0.000 claims abstract description 8
- 238000001990 intravenous administration Methods 0.000 claims abstract description 8
- 229940111202 pepsin Drugs 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000011534 incubation Methods 0.000 claims abstract description 5
- 238000005194 fractionation Methods 0.000 claims abstract description 3
- 238000004519 manufacturing process Methods 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims 1
- 238000000502 dialysis Methods 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 230000003171 anti-complementary effect Effects 0.000 abstract description 3
- 230000002378 acidificating effect Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 102000003839 Human Proteins Human genes 0.000 abstract 1
- 108090000144 Human Proteins Proteins 0.000 abstract 1
- 208000001953 Hypotension Diseases 0.000 abstract 1
- 230000002744 anti-aggregatory effect Effects 0.000 abstract 1
- 230000002959 anti-hypotensive effect Effects 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 208000021822 hypotensive Diseases 0.000 abstract 1
- 230000016784 immunoglobulin production Effects 0.000 abstract 1
- 230000006641 stabilisation Effects 0.000 abstract 1
- 238000011105 stabilization Methods 0.000 abstract 1
- 230000000721 bacterilogical effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000010494 opalescence Effects 0.000 description 1
- 230000014207 opsonization Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001303 quality assessment method Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
Sposob přípravy 1'udských .imunoglobulínov pre intravenóznu aplikáeiu, pri ktorom antikomplementárna aktivita a hypotenzívny účinok imunoglobulínov sa znižuje inkubáclou pri teplote -f-37 CC a kyslom pH za přítomnosti pepsínu v prostředí maltózy. Maltóza má antiagregačný a stabilizačný účinok na 1'udskě bielkoviny, čím zabraňuje nežiadúcim štrukturálnym změnám imunoglobulínov. Přítomnost maltózy tiež priaznivo vplýva na rýchlosť rozpúšťania botového výrobku. Podstata spósobu výroby 1'udských imunoglobulínov- pre intravenóznu aplikáeiu spočívá v -tom, že imunoglobulíny získané etanolovou frakcionáciou sa v prostředí 0,1 až 5 % maltózy pri pH 3,8 až 4,2 a teplote -j-37 stupňov C inkubuje za přítomnosti pepsínu po dobu 18 až 25 hodin. Nízkomolekulárne látky sa odstraňujú dialýzou oproti 0,1 až 5 % roztoku maltózy. Dialyzát po- nastavení příslušných p-arametrov sa sterilizuje filtráciou, rožplňuje a lyofilizuje.A method of preparing human immunoglobulins for intravenous administration anti-complementary activity and hypotensive the effect of immunoglobulins is reduced by incubation at -f-37 ° C and acidic pH presence of pepsin in the maltose environment. Maltose has anti-aggregation and stabilization effect on 1'human protein, thereby preventing undesirable structural changes in immunoglobulins. The presence of maltose also has a favorable effect affects the dissolution rate of the bot product. The nature of the human immunoglobulin production method for intravenous administration rests in that the ethanol-derived immunoglobulins fractionation in an environment of 0.1 to 5% maltose at pH 3.8 to 4.2 and temperature -j-37 incubated in the presence of pepsin for 18 to 25 hours. low molecular weight the substances are removed by dialysis versus 0.1 to 5% maltose solution. Post-dialysis dialysis appropriate p-parameters are sterilized by filtration, fill and lyophilize.
Description
Vynález sa .lýka, sposobu, přípravy Iudských .iinunoglolj ulili ov pre imtravenóznu aplikáciu, pří ktorom ša dosiahne zníženie antikomplěmentárnej aktivity a hypotenzívneho účinku imunoglobulínov.The present invention is directed to methods for preparing human immunoglobulins for use in an intravenous application, which achieve a reduction in the anti-complementary activity and the hypotensive effect of immunoglobulins.
V súčasnej době imunoglobulíiny používané k liíntravenéznej aplikácii sa u nás pripravujú tým spůsobom, že z imunoglobulínov izolovaných etanolovou frakcionáciou sa odstraňujú látky s antikomplementárnou aktivitou a hypoteinzívnym účinkom, buď dialýzou pomocou dialyzačných čriev (ŠtěpánekNowadays, immunoglobulins used for li-intravenous application are prepared in the Czech Republic in such a way that immunoglobulins isolated by ethanol fractionation remove substances with anticomplementary activity and hypoteinsive effect, either by dialysis using dialysis intestines (Štěpánek)
I.: AO 202 180 a AO 208 86Š), alebo pomocou ultrafiltračného zariadenia s definovanými velkosťami pórov.I .: AO 202 180 and AO 208 86Š), or using ultrafiltration equipment with defined pore sizes.
Nedostatkom takto připraveného výrobku je dlhá doba rozpustnosti a možnosť reagregácie molekúl imunoglobulínov v priebehu technologického postupu, resp. počas skladovania.The disadvantage of this product is long solubility time and possibility of reagregation of immunoglobulin molecules during the technological process, resp. during storage.
V zahraničí ,k přípravě imunoglobulínov pre intravenóznu aplikáciu sa používajú technologické postupy štiepenia imunoglobulínov pepsínom (Koch F.: Dtsch. med. Wschr. 88 : 282,, 1963, Schultz Η. E., Schwick. G.: Dtsch. med. Wschr. 87 :1643, 19o2j, popřípadě opíacovaním imuhoglohulínoy, inkubáciou pri kyslom pH za přítomnosti pepslnu (Barandun S., Kistler P., Jeunet F., Istiker H.: Vox Sang. 7, 1962, str. 157 ,až 174).Abroad, to prepare immunoglobulins for intravenous administration, technological procedures for the cleavage of immunoglobulins by pepsin are used (Koch F .: Dtsch. Med. Wschr. 88: 282, 1963, Schultz, E., Schwick. G .: Dtsch. Med. Wschr. 87: 1643, 1922, optionally by repeating the immunoglobulin, by incubating at acidic pH in the presence of pepsin (Barandun S., Kistler P., Jeunet F., Istiker H., Vox Sang. 7, 1962, pp. 157-174).
Nedostatkom takto vyrobených prípravkov sú změněné biologické vlastnosti, ako schopnost opsonizácie a iné biologické aktivity.A disadvantage of the compositions thus produced is altered biological properties, such as opsonization ability and other biological activities.
Podstata nového- sposobu přípravy ludských imunoglobulínov pre intravenóznu , aplikáciu spočívá v tom, že 5 až 8 % roztok ’ iihunoglobulínov o-bsahujúci 0,1 -až 5 o/o mal•tózy pri pH 3,8 až 4,2 a teplote 36 až 38 °C sa inkubuje za přítomnosti pepsínu po dobu 18 až 26 hodin. Po ukončení inkubácie pH rožtofcu sa upravuje na hodnotu 6,8 až 7,0 a potom sa roztok dialyzuje oproti 0,1 ažThe essence of the novel process for the preparation of human immunoglobulins for intravenous administration is that a 5-8% solution of immunoglobulins containing 0.1 to 5% maltose at a pH of 3.8 to 4.2 and a temperature of 36 to 36% to 38 ° C is incubated in the presence of pepsin for 18-26 hours. After incubation, the pH of the rhombus is adjusted to 6.8 to 7.0 and then dialyzed against 0.1 to 7.0.
Hodhoténie kvality výrobku Stanovené parametre vzhlad rozpustnost antikom. aktivita hypotenzívny účinok (pokles tlaku)Product quality assessment Specified parameters appearance solubility antique. activity hypotensive effect (pressure drop)
Výrobok připravený stavajúcou techn-ol.A product prepared by an existing technol.
mierna opalesce-ncia 30‘slight opalescence 30 ‘
0,71 j/mg bielk. —5,0 % 0,0-0,1 % roztoku maltózy, Dlalyzát po nastavení, příslušných parametrov sa,,filtru je ,cez; bakteriologické filtre, rozplňujé, namrazuje ,a lyofilizuje.0.71 j / mg bleach. —5.0% 0.0-0.1% Maltose Solution, Dlalysate after setting, the appropriate parameters of the filter are, via ; bacteriological filters, fill, freeze, and lyophilize.
Navrhnutý sposob přípravy ludských imunoglobulínov pre intravenóznu aplikáciu odstraňuje nežiaduce vlastnosti imunoglobulínov, pričom pri technolo-gickom postupe sa dbá o. to, -aby v čo najmenšej miere .bola narušená štruktúra imunoglobulínov.The proposed process for the preparation of human immunoglobulins for intravenous administration removes undesirable properties of immunoglobulins, with care being taken in the technological process. that the structure of the immunoglobulins is impaired as little as possible.
Příklad 1Example 1
K 100 ml 5 až 8 % roztoku imunoglobulínov obsahujúcich 1,5 % maltózy, ktorých pH sa upraví na hodnotu 3,8 až 4,2, přidá sa 50 miligr-amov pepsínu -o účinnosti 1 : 110 000 a potom sa inkubuje pri teplote. -)-37 °C po dobu 25 hodíp. Po skončení inkubácie pH roztoku sa upraví na hodnotu 6,8 a diallyzuje oproti 0,1 až 5 % roztoku maltózy pri teplotě -)-4 °C po dobu 12 až 48 hodin. Po úpravě obsahu bielkovín na hodnotu 4,5 až 5,5 % sa roztok imunoglobulínov filtruje cez bakteriologické filtre, rozplňujé, namr-azuje a lyofilizuje.To 100 ml of a 5 to 8% solution of immunoglobulins containing 1.5% maltose, whose pH is adjusted to 3.8 to 4.2, add 50 milligrams of pepsin at an efficacy of 1: 110,000 and then incubate at a temperature of . -) - 37 ° C for 25 hours. After the incubation is complete, the pH of the solution is adjusted to 6.8 and dialyzed against a 0.1 to 5% maltose solution at - 1-4 ° C for 12 to 48 hours. After adjusting the protein content to 4.5-5.5%, the immunoglobulin solution is filtered through bacteriological filters, filled, frozen and lyophilized.
P r i k 1 a d 2Example 1 and d 2
K 100 ml 5 až 8 % roztoku imunoglobulínov obsahujúcich 1,0 % maltózy, ktorých pil sa upraví na hodnotu 3,8 až 4,2, přidá sa 50 mg pepsínu o účinnosti 1 : 10 000 a potom sa inkubuje pri teplote -j-37 °C po dobu 18 hcidín. Po -skončení inkubácie sa pH roztoku upraví na hodnotu 6,8 a di-alyzuje oproti 0,1 až 5 % roztoku maltózy pri teplote +4 °C po dobu 12 až 48 hodin. Po úpravě % bielkovín na hodnotu 4,5 až 5,5 sa rozltok imunoglobulínov filtruje cez bakteriologické filtre, rozplňujé, namrazuje a lyofilizuje.To 100 ml of a 5 to 8% solution of immunoglobulins containing 1.0% maltose whose pH is adjusted to 3.8 to 4.2, add 50 mg of pepsin with an efficacy of 1: 10,000 and then incubate at -j- 37 ° C for 18 hcidin. After incubation, the pH of the solution is adjusted to 6.8 and dialyzed against a 0.1 to 5% maltose solution at +4 ° C for 12 to 48 hours. After adjusting the% protein to 4.5-5.5, the immunoglobulin solution is filtered through bacteriological filters, filled, frozen and lyophilized.
Výrobok připravený podlá PV čirý .·Product prepared according to PV clear ·
2‘2 '
0,08 j/mg bielk. .0.08 j / mg bleach. .
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS844767A CS239838B1 (en) | 1984-06-22 | 1984-06-22 | Processing of humen imunoglobuline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS844767A CS239838B1 (en) | 1984-06-22 | 1984-06-22 | Processing of humen imunoglobuline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS476784A1 CS476784A1 (en) | 1985-06-13 |
| CS239838B1 true CS239838B1 (en) | 1986-01-16 |
Family
ID=5391171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS844767A CS239838B1 (en) | 1984-06-22 | 1984-06-22 | Processing of humen imunoglobuline |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS239838B1 (en) |
-
1984
- 1984-06-22 CS CS844767A patent/CS239838B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS476784A1 (en) | 1985-06-13 |
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