CS272716B1 - Method of igg + iga and igg + igm-base immunoglobulin preparations for intramuscular administration from blood mixed immunoglobulin igg + iga + igm-base preparation - Google Patents
Method of igg + iga and igg + igm-base immunoglobulin preparations for intramuscular administration from blood mixed immunoglobulin igg + iga + igm-base preparation Download PDFInfo
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- CS272716B1 CS272716B1 CS709887A CS709887A CS272716B1 CS 272716 B1 CS272716 B1 CS 272716B1 CS 709887 A CS709887 A CS 709887A CS 709887 A CS709887 A CS 709887A CS 272716 B1 CS272716 B1 CS 272716B1
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- 108060003951 Immunoglobulin Proteins 0.000 title claims abstract description 22
- 102000018358 immunoglobulin Human genes 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000007918 intramuscular administration Methods 0.000 title claims abstract description 6
- 210000004369 blood Anatomy 0.000 title claims abstract description 4
- 239000008280 blood Substances 0.000 title claims abstract description 4
- 238000000034 method Methods 0.000 title claims description 10
- 239000000243 solution Substances 0.000 claims abstract description 33
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 21
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 20
- 238000004108 freeze drying Methods 0.000 claims abstract description 15
- 239000012460 protein solution Substances 0.000 claims abstract description 13
- 238000001042 affinity chromatography Methods 0.000 claims abstract description 11
- 238000005227 gel permeation chromatography Methods 0.000 claims abstract description 11
- 238000004255 ion exchange chromatography Methods 0.000 claims abstract description 11
- 239000002244 precipitate Substances 0.000 claims abstract description 11
- 238000001914 filtration Methods 0.000 claims abstract description 10
- 239000011780 sodium chloride Substances 0.000 claims abstract description 10
- 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 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 9
- 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 9
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims abstract description 9
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims abstract description 9
- 239000008103 glucose Substances 0.000 claims abstract description 9
- 235000000346 sugar Nutrition 0.000 claims abstract description 9
- 150000008163 sugars Chemical class 0.000 claims abstract description 9
- 239000006228 supernatant Substances 0.000 claims abstract description 8
- 238000005119 centrifugation Methods 0.000 claims abstract description 6
- 239000011541 reaction mixture Substances 0.000 claims abstract description 5
- 239000013049 sediment Substances 0.000 claims abstract description 4
- 229940072221 immunoglobulins Drugs 0.000 claims description 8
- 238000000108 ultra-filtration Methods 0.000 claims description 6
- 210000002966 serum Anatomy 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 229920000298 Cellophane Polymers 0.000 claims description 4
- 238000003149 assay kit Methods 0.000 claims description 4
- 238000000502 dialysis Methods 0.000 claims description 4
- 230000000521 hyperimmunizing effect Effects 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- IYLLULUTZPKQBW-UHFFFAOYSA-N Acrinol Chemical compound CC(O)C(O)=O.C1=C(N)C=CC2=C(N)C3=CC(OCC)=CC=C3N=C21 IYLLULUTZPKQBW-UHFFFAOYSA-N 0.000 claims description 3
- 238000012869 ethanol precipitation Methods 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 claims description 2
- 230000001147 anti-toxic effect Effects 0.000 claims description 2
- 230000000840 anti-viral effect Effects 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 230000000087 stabilizing effect Effects 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 238000004090 dissolution Methods 0.000 claims 1
- 230000001376 precipitating effect Effects 0.000 claims 1
- 238000004062 sedimentation Methods 0.000 claims 1
- 238000002156 mixing Methods 0.000 abstract 1
- 230000006641 stabilisation Effects 0.000 abstract 1
- 238000011105 stabilization Methods 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 3
- 235000011130 ammonium sulphate Nutrition 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 2
- 229960002446 octanoic acid Drugs 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Vynález sa týká sposobu přípravy imunoglobulinových preparátov na báze IgG+IgA a IgG+IgM pre i.m. podanie z krvného zmesného imunoglobulinového preparátu na báze IgG+ +IgA+lgM, ktorý bol připravený z normálnej alebo hyperimunnej plazmy připadne z normálneho, retroplacentárného alebo hyperimunného séra s definovanou antibakteriálnou, antitoxickou alebo antivirovou protilátkovou aktivitou.The invention relates to a process for the preparation of immunoglobulin preparations based on IgG + IgA and IgG + IgM for i.m. administration from a blood mixed immunoglobulin preparation based on IgG + + IgA + IgM prepared from normal or hyperimmune plasma, respectively from normal, retroplacental or hyperimmune serum with defined antibacterial, antitoxic or antiviral antibody activity.
Na přípravu imunoglobulinových preparátov na báze IgG+IgA a IgG+IgM pre i.m. podanie použil Audran a spol. (Audran R., Pejaudier L., Steinbuch M.í Rev.Franc.Transf.Immunol.Hematol. 18,119,1975) kombinovaná metodu precipitácie na báze alkoholickej frakcionácie spojené j s účinkom kyseliny kaprylovej, Wickerhauser a Hao (Wickerhauser M., Hao Y.L.: Vox Sang. 23,119,1972) použili polyetylenglykol za spoluúčasti zinočnatých solí a síranu amonného, pričom Schwick a spol. (Schwick H.G., Fischer J., Geiger H.: v knihe Immunoglabulins, biological aspects and clinical uses National Acad.Sciences Washington DC 1970,str.116) použili kombinovaná precipitačnú metodu na báze síranu amonného a rivanolu.For the preparation of immunoglobulin preparations based on IgG + IgA and IgG + IgM for i.m. administration was used by Audran et al. (Audran R., Pejaudier L., Steinbuch M. Rev. France.Transf.Immunol.Hematol. 18,119, 1975) The combined alcoholic fractionation precipitation method associated with caprylic acid, Wickerhauser and Hao (Wickerhauser M., Hao YL) (Vox Sang. 23,119,1972) used polyethylene glycol with the participation of zinc salts and ammonium sulfate, with Schwick et al. (Schwick, H. G., Fischer, J., Geiger, H .: in the book Immunoglabulins, Biological Aspects and Clinical Uses of the National Acad. Sciences Washington DC 1970, p.116) used a combined precipitation method based on ammonium sulfate and rivanol.
Podstatou sposobu pripravy imunoglobulinových preparátov na báze IgG+IgA a IgG+IgM pre i.m. podanie je precipitácia bielkovinného roztoku na báze IgG+IgA+IgM etanolom, ktorý vyzráža z roztoku bielkovinný precipitát bohatý na IgG+IgM a v roztoku zostáva IgG+IgA pričom bielkovinný roztok na báze IgG+IgA+IgM o koncentrácii 5 až 100 gramov na liter, s optimom 20 až 40 gramov na liter, pri rozmedzi pH 4,0 až 8,0, s optimom 6,8-7,2, pri koncentraci! etanolu 6 až 10 obj.%, vztiahnuté na celkový objem reakčnej zmesi, pri konečnej teplote -5 °C až - 12 °C z ktorého bol vyprecipitovaný sediment v podobě bielkovinného precipitátu sa mieša alebo nechává stať při uvedených podmienkach 5 až 12 hodin a potom sa přikročí ku oddeleniu precipitátu například centrifugáciou pri teplote - 5 °C až - 12 °C.The principle of preparation of immunoglobulin preparations based on IgG + IgA and IgG + IgM for i.m. administration is the precipitation of an IgG + IgA + IgM-based protein solution with ethanol, which precipitates an IgG + IgM-rich protein precipitate from the solution and IgG + IgA remains in solution with an IgG + IgA + IgM protein solution at a concentration of 5 to 100 grams per liter, with an optimum of 20 to 40 grams per liter, at a pH range of 4.0 to 8.0, with an optimum of 6.8-7.2, at a concentration! ethanol, 6-10 vol.%, based on the total volume of the reaction mixture, at a final temperature of -5 ° C to -12 ° C from which the protein precipitate precipitated was stirred or allowed to stand under the above conditions for 5-12 hours and then the precipitate is separated, for example, by centrifugation at - 5 ° C to - 12 ° C.
Precipitát bohatý na IgG+IgM sa rozpúšťá v roztoku chloridu sodného v apyrogennej vodě o teplote 0 °C až + 6 °C na koncentráciu 3 až 9 gramov chloridu sodného na liter, hodnota pH sa upraví na 6,4 až 7,4, v případe potřeby sa podrobí ďalšiemu spracovaniu například pomocou gelovej, iontomennej alebo afinitnej chromatografie, pričom před koncovou lyofilizáciou sa roztok stabilizuje přidáním glukózy, maltózy alebo iných cukrov, sterilizuje sa například filtráciou, rozplňuje sa a lyofillzuje.The IgG + IgM-rich precipitate is dissolved in a solution of sodium chloride in pyrogen-free water at a temperature of 0 ° C to + 6 ° C to a concentration of 3 to 9 grams of sodium chloride per liter, the pH is adjusted to 6.4 to 7.4. if desired, it is subjected to further processing by, for example, gel, ion-exchange or affinity chromatography, wherein the solution is stabilized by the addition of glucose, maltose or other sugars prior to final lyophilization, sterilized, for example, by filtration, filled and lyophilized.
Supernatant bohatý na IgG+IgA sa zbavuje etanolu například lyofilizáciou alebo opakovanou ultrafiltráciou, připadne dialyzou cez vhodná membránu akou je například celofánové potrubie, v případe potřeby sa zakoncentrováva na 20 až 50 gramov bielkovín na liter, přidává sa také množstvo chloridu sodného, aby jeho koncentrácia v roztoku bola 3 až 9 gramov na liter, hodnota pH sa upraví na 6,4 až 7,4, v případe potřeby sa podrobí 5alšiemu spracovaniu například pomocou gelovej, iontomennej alebo afinitnej chromatografie, pričom před koncovou lyofilizáciou sa roztok stabilizuje přidáním glukózy, maltózy alebo iných cukrov, sterilizuje sa například filtráciou, rozplňuje sa a lyofillzuje.The IgG + IgA-rich supernatant is freed of ethanol, for example, by lyophilization or repeated ultrafiltration, or by dialysis through a suitable membrane such as cellophane, if necessary, concentrated to 20 to 50 grams of protein per liter, adding sodium chloride to a concentration in the solution was 3 to 9 grams per liter, the pH was adjusted to 6.4 to 7.4, if necessary subjected to further treatment, for example by gel, ion-exchange or affinity chromatography, the solution being stabilized by the addition of glucose, maltose before lyophilization or other sugars, sterilized, for example, by filtration, filled and lyophilized.
Vynález je 5alej objasněný na príkladoch prevedenia, ktorými jeho rozsah nieje ani obmedzený ani vyčerpaný.The invention is further elucidated by means of exemplary embodiments in which its scope is neither limited nor exhaustive.
Příklad 1Example 1
Východziou súrovinou móže byť bielkovinná pasta precipitátu imunoglobulinov IgG+IgA+ +IgM získaná pomocou kyseliny kaprylovej (Blatrix G., Israel 0., Reinert Ph., Griscelli G., Steinbuch M.: La Nouvelle Presse Medicale 5,1193,1976).The starting material may be a protein paste of an immunoglobulin precipitate of IgG + IgA + + IgM obtained by caprylic acid (Blatrix G., Israel O., Reinert Ph., Griscelli G., Steinbuch M .: La Nouvelle Presse Medicale 5,1193, 1976).
Bielkovinný materiál nariedime destilovanou apyrogennou vodou o teplote 0 °C až + 6 °C tak, aby koncentrácia bielkovín sa nachádzala v rozmedzi 5 až 100 gramov na liter, s optimom 20 až 40 gramov na liter. Hodnota pH takto vzniknutého roztoku bývá zpravidla v rozmedzi 4,0 až 8,0. Takto připravený roztok v optimálnej koncentrácii bielkovín má zpravidla zloženie v rozmedzi 9 až 12 g IgG, 5 až 8 g IgA, 1 až 2 g IgM. Všetky koncentrácie imunoglobulinov sú vztahované na liter roztoku a boli stanovené pomocou Q antisér, výrobku fy. USOL Praha.Dilute the proteinaceous material with distilled pyrogen-free water at a temperature of 0 ° C to + 6 ° C such that the protein concentration is in the range of 5 to 100 grams per liter, with an optimum of 20 to 40 grams per liter. The pH of the solution thus obtained is generally in the range of 4.0 to 8.0. The solution thus prepared at an optimal protein concentration generally has a composition in the range of 9-12 g IgG, 5-8 g IgA, 1-2 g IgM. All concentrations of immunoglobulins are based on 1 liter of solution and were determined using Q antisera, a product of fy. USOL Praha.
Μ,Μ.
CS 272716 Bl 2CS 272716 B1 2
Rozdelenie roztoku obsahujúceho IgG+IgA+IgM na bielkovinnú pastu bohatú na IgG+IgM a na roztok bohatý na IgG+IgA sa prevádza pomocou precipitácie etanolom pri rozmedzí pH 4,0 až 8,0, s optimom 6,8 až 7,2, pri koncentrácii etanolu 6 až 10 obj. vztahované na celkový objem reakčnej zmesi, pri konečnej teplote - 5 °C až - 12 °C pričom vyprecipitovaný sediment sa mieša alebo nechává stát’ pri uvedených podmienkách 5 až 12 hodin.The separation of the IgG + IgA + IgM containing solution into an IgG + IgM rich protein paste and an IgG + IgA rich solution is performed by ethanol precipitation at a pH range of 4.0 to 8.0, with an optimum of 6.8 to 7.2, at an ethanol concentration of 6 to 10 vol. based on the total volume of the reaction mixture, at a final temperature of - 5 ° C to - 12 ° C, wherein the precipitated sediment is stirred or allowed to stand under the above conditions for 5 to 12 hours.
Bielkovinný precipitát bohatý na IgG+IgM po následnej separácii, například centrifugáciou, při teplote - 5 °C až - 12 °C sa suspenduje vo vodnom roztoku chloridu sodného v apyrogennej vodě o teplote 0 °C až + 6 °C o koncentrácii 3 až 9 g na liter na koncehtráciu bielkovín 20 až 50 g na liter, upraví sa hodnota pH na 6,4 až 7,4 pričom sa získá bielkovinný roztok, kde na IgG v rozmedzí 9 - 12 g připadá 1 - 2 g IgA a 2 - 3g IgM. Všetky koncentrácie imunoglobulinov sú vztahované na liter roztoku pričom boli stanovené pomocou testovacích súprav, ktoré vyrába fy. USOL Praha. V případe potřeby sa bielkovinný roztok podrobí ďalšiemu zpracovaniu například pomocou gelovej, iontomennej alebo afinitnej chromatografie, před koncovou lyofilizáciou sa roztok stabilizuje například přidáním glukózy, maltózy alebo iných cukrov, sterilizuje sa například filtráciou, rozplňuje sa a lyofilizuje.IgG + IgM-rich protein precipitate after subsequent separation, for example by centrifugation, at -5 ° C to -12 ° C, is suspended in aqueous sodium chloride solution in pyrogen-free water at 0 ° C to + 6 ° C at a concentration of 3 to 9 g per liter for protein extractions of 20 to 50 g per liter, the pH is adjusted to 6.4 to 7.4 to obtain a protein solution where the IgG in the range of 9-12 g comprises 1-2 g IgA and 2-3 g IgM. All concentrations of immunoglobulins are based on 1 liter of solution and were determined using assay kits manufactured by fy. USOL Praha. If desired, the protein solution is subjected to further processing, for example by means of gel, ion-exchange or affinity chromatography, stabilizing the solution, for example by the addition of glucose, maltose or other sugars, prior to final lyophilization, sterilizing for example by filtration, filling and lyophilizing.
Supernatant je bielkovinný roztok bohatý na IgG+IgA kde na 5-6 g IgG připadá 10 - 12,5 g IgA a 0,1 - 0,2 g IgM. Všetky koncentrácie imunoglobulinov sú vztahované na liter roztoku pričom boli stanovené pomocou testovacích súprav, ktoré vyrába fy. USOL Praha.. Supernatant bohatý na IgG+IgA sa zbavuje etanolu například lyofilizáciou alebo opakovanou ultrafiltráciou alebo dialyzou cez vhodnú membránu, například cez celofánové potrubie, v případe potřeby sa zakoncentrováva na koncentráciu bielkovín 20 až 50 g na liter, například ultrafiltráciou alebo vymrazovaním, přidává sa chlorid sodný do koncentrácie 3 až 9 g na liter, upraví sa pH na 6,4 až 7,4. V případe potřeby sa podrobí ďalšiemu spracovaniu například pomocou gelovej, iontomennej alebo afinitnej chromatografie před koncovou lyofilizáciou sa roztok stabilizuje například přidáváním glukózy, maltózy alebo iných cukrov, sterilizuje sa například filtráciou, rozplňuje sa a lyofilizuje.The supernatant is a protein solution rich in IgG + IgA where 5-6 g of IgG account for 10-12.5 g of IgA and 0.1-0.2 g of IgM. All concentrations of immunoglobulins are based on a liter solution and were determined using assay kits manufactured by fy. The IgG + IgA-rich supernatant is freed of ethanol, for example, by lyophilization or repeated ultrafiltration or dialysis through a suitable membrane, for example through cellophane piping, if necessary concentrated to a protein concentration of 20 to 50 g per liter, for example by ultrafiltration or freeze drying. sodium chloride to a concentration of 3 to 9 g per liter, adjusting the pH to 6.4 to 7.4. If desired, it is subjected to further processing, for example by means of gel, ion-exchange or affinity chromatography, before final lyophilization, the solution is stabilized, for example by adding glucose, maltose or other sugars, sterilized, for example, by filtration, filled and lyophilized.
Hodnoty koncentrácie jednotlivých imunoglobulinov v lyofilizovaných preparátoch IgG+IgM a IgG+IgA po rozpuštění sú závislé od koncentrácie uvedených imunoglobulinov vo východnej plazme, sere alebo medzifrakcii ako aj od přesnosti testovacej súpravy.The concentration values of individual immunoglobulins in lyophilized preparations of IgG + IgM and IgG + IgA after reconstitution depend on the concentration of said immunoglobulins in eastern plasma, serum or intermediate fraction as well as on the accuracy of the test kit.
Příklad 2Example 2
Na přípravu imunoglobulinových preparátov na báze IgG+IgA+IgM použil Schwick a spol. síran amonný v kombinácii s rivanolom (Schwick H.G., Fischer 3., Geiger H.: Progr.Immunobiol.Stand. 4,86,1970; Schwick H.G.: Vox Sang. 23,82,1972) a Pejaudier a spol. kyselinu boritú (Pejaudier L., Audran R., Steinbuch M.: Vox Sang. 23,165,1972). Východziou surovinou může byť bielkovinná pasta IgG+IgA+IgM v purifikovanom stave izolovaná aj pomocou iných metod.To prepare immunoglobulin preparations based on IgG + IgA + IgM, Schwick et al. ammonium sulfate in combination with rivanol (Schwick H.G., Fischer 3., Geiger H .: Progr.Immunobiol.Stand. 4,86,1970; Schwick H.G .: Vox Sang. 23,82,1972) and Pejaudier et al. boric acid (Pejaudier L., Audran R., Steinbuch M., Vox Sang. 23,165,1972). The starting material can be isolated in an purified state of IgG + IgA + IgM protein by other methods.
Východziou surovinou může byť aj bielkovinný roztok IgG+IgA+IgM získaný například podía A0 247 303; A0 208 867 alebo pomocou gelovej, iontomennej alebo afinitnej chromatografie priamo z plazmy, séra alebo .z medzifrakcie. Bielkovinná pasta sa uvedie do roztoku, a bielkovinný roztok sa spracováva v ďalšom postupe ako v příklade 1.The starting material may also be an IgG + IgA + IgM protein solution obtained, for example, from A0 247 303; A0 208 867 or by means of gel, ion-exchange or affinity chromatography directly from plasma, serum or intermediate. The protein paste is dissolved, and the protein solution is processed as in Example 1.
Claims (4)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS709887A CS272716B1 (en) | 1987-10-02 | 1987-10-02 | Method of igg + iga and igg + igm-base immunoglobulin preparations for intramuscular administration from blood mixed immunoglobulin igg + iga + igm-base preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS709887A CS272716B1 (en) | 1987-10-02 | 1987-10-02 | Method of igg + iga and igg + igm-base immunoglobulin preparations for intramuscular administration from blood mixed immunoglobulin igg + iga + igm-base preparation |
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| Publication Number | Publication Date |
|---|---|
| CS709887A1 CS709887A1 (en) | 1990-06-13 |
| CS272716B1 true CS272716B1 (en) | 1991-02-12 |
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|---|---|---|---|
| CS709887A CS272716B1 (en) | 1987-10-02 | 1987-10-02 | Method of igg + iga and igg + igm-base immunoglobulin preparations for intramuscular administration from blood mixed immunoglobulin igg + iga + igm-base preparation |
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| Country | Link |
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| CS (1) | CS272716B1 (en) |
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1987
- 1987-10-02 CS CS709887A patent/CS272716B1/en unknown
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| CS709887A1 (en) | 1990-06-13 |
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