LT3419B - Composition for stabilizing blood plasma during pasteurization, method of pasteurization and plasma preparing by this method - Google Patents

Composition for stabilizing blood plasma during pasteurization, method of pasteurization and plasma preparing by this method Download PDF

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LT3419B
LT3419B LTIP264A LTIP264A LT3419B LT 3419 B LT3419 B LT 3419B LT IP264 A LTIP264 A LT IP264A LT IP264 A LTIP264 A LT IP264A LT 3419 B LT3419 B LT 3419B
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plasma
composition
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pasteurization
lysine
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Miryana Burnouf
Thierry Burnouf
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Centre Regional De Transfusion
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Abstract

Composition for stabilizing blood plasma, whole or lacking cryoproteins, during pasteurization. The composition according to the invention is used for pasteurizing substantial volumes of plasma (up to several hundreds of litres). The invention also concerns a process for the pasteurization of plasma using said stabilizing composition. The pasteurized plasma obtained is for therapeutic use.

Description

Išradimas liečia kompoziciją, įgalinančią stabilizuoti kraujo plazmą pasterizavimo metu, patį būdą, naudojant minėtą kompoziciją, ir gautus tokiu būdu plazmos tirpalus, skirtus ypač plazmos ir kraujo krešėjimo V, XI ir XIII faktorių pakaitalų terapijai.The present invention relates to a composition capable of stabilizing blood plasma during pasteurisation, the same process using said composition, and the resulting plasma solutions, particularly for the treatment of plasma and coagulation factor V, XI and XIII.

Visa žmogaus plazma ar plazma, atskirta nuo krioproteinų, panaudojama pakaitalų terapijoje, esant sunkiems nudegimams, pacientams, patyrusiems dideles traumas arba rimtas chirurgines operacijas, t. y. visais atvejais, kad netenkama didelio skysčio kiekio.All human plasma or plasma isolated from cryoprotein is used in replacement therapy for severe burns, in patients who have sustained major trauma or in serious surgery, i. y. in all cases, that a large amount of fluid is lost.

Paprastai šio tipo terapijoje naudojama plazma, gauta iš individualių donorų, sveikų ir iš anksto patikrintų asmenų, išvengiant rizikos, pernešant virusinius susirgimus. Vienok ši procedūra neužtikrina virusinio užkrėtimo negalimumo priešserologiniame periode, ypač įvairiais hepatito virusais ir AIDS virusu.Plasma from individual donors, healthy and pre-screened individuals is commonly used in this type of therapy to avoid the risk of transmitting viral diseases. However, this procedure does not ensure that viral infection is not possible in the pre-serological period, especially with various hepatitis viruses and AIDS virus.

Todėl reikalinga sukurti virusinės inaktyvacijos metodą, kuris neturėtų poveikio įvairioms plazmos biologinėms funkcijoms.It is therefore necessary to develop a method for viral inactivation that does not affect the various biological functions of plasma.

Buvo įrodyta, jog hepatito B virusas yra pilnai inaktyvuoj amas kaitinant prie 60°C 10 vai., esant 0.5 M natrio citrato (Tabor ir kt. Trombosis Res., 22, 1981, 233-238). Vienok šis apdorojimas iššaukia kai kurių plazmos proteinų biologinio aktyvumo praradimą (Tabor ir kt., ir Barrowcliffe ir kt., Fr. J. Haematology, 55, 1983, 37-47).Hepatitis B virus has been shown to be completely inactivated by heating at 60 ° C for 10 hours in 0.5 M sodium citrate (Tabor et al., Thrombosis Res., 22, 1981, 233-238). However, this treatment causes loss of biological activity of some plasma proteins (Tabor et al., And Barrowcliffe et al., Fr. J. Haematology, 55, 37-47 (1983)).

Yra įrodyta, jog įvairūs proteinai, reikšmingi terapijai, išskirti ir išvalyti iš kraujo plazmos, atlaiko klasikinį pasterizavimą prie 60°C 10 vai. laikotarpyje, esant įvairiems stabilizatoriams. Be to, parodyta, jog molekulės, stabilizuojančios vieną biologinį aktyvumą, gali būti visiškai neefektyvios kitų aktyvumų atžvilgiu.Various proteins of interest in therapy, isolated and purified from plasma, have been shown to withstand classic pasteurization at 60 ° C for 10 hours. period with various stabilizers. In addition, it has been shown that molecules that stabilize one biological activity may not be completely effective against the other activities.

Taigi, albuminas gali būti stabilizuojamas acetiltriptofanu ir kaprilatu (Gellis ir kt., J. Clin. Invest., 27, 1948, 238-244), tuo tarpu šie stabilizatoriai nerodo poveikio plazminogeno atžvilgiu. Trombinas gali būti stabilizuojamas aukštomis gliukozidų koncentracijomis (Seegers. Arch. Biochem., 3, 1944, 363-367), bet jos neapsaugo protrombino. Amino rūgščių ir karbohidratų priedas duoda gerus rezultatus VIII faktoriaus ir III antitrombino atžvilgiu (žiūr. VFR patentą Nr. 29 16 711).Thus, albumin can be stabilized with acetyltryptophan and caprylate (Gellis et al., J. Clin. Invest., 27, 1948, 238-244), whereas these stabilizers show no effect on plasminogen. Thrombin can be stabilized by high concentrations of glucosides (Seegers. Arch. Biochem. 3, 1944, 363-367), but does not protect prothrombin. The addition of amino acids and carbohydrates gives good results with respect to factor VIII and antithrombin III (see VFR Patent No. 2916711).

Europos patentas Nr. 0 035 204 aprašo a-antitripsino, III antitrombino, prekalikreino, fibronektino ir VIII faktoriaus stabilizavimą polialkoholių pagalba, kaip vieną iš paskutinių pavyzdžių nurodydamas sacharozę; vienok parodyta, kad tokiomis pačiomis sąlygomis IX faktorius ir prekalikreinas praranda savo visą terapinį aktyvumą.European patent no. 0 035 204 describes stabilization of α-antitrypsin, antithrombin III, precalicrein, fibronectin and factor VIII by polyalcohols, with sucrose as one of the last examples; however, it is shown that, under the same conditions, factor IX and prekalikrein lose all their therapeutic activity.

Šie skirtingi eksperimentiniai duomenys patvirtina tą nuomonę, jog virusinė visos plazmos (šviežios plazmos, užšaldytos šviežios plazmos ar krionusodinto supernatanto) inaktyvacija pasterizavimo būdu.These different experimental data support the notion that viral inactivation of whole plasma (fresh plasma, frozen fresh plasma or cryoprecipitated supernatant) by pasteurization.

Kadangi medicinoje jaučiamas pareiškėjas turėjo tikslą užtikrinančią vienalaikę terapijai, biologinio aktyvumo pasterizavimo metu.Because the medical-minded applicant had a goal to ensure simultaneous therapy during the pasteurization of biological activity.

Įskaitant tai, jog sorbitas prieš terminę denatūraciją, tarp plazmos pavyzdžių ir negali būti pasiekta visos plazmos trūkumas, pasiūlyti kompoziciją, sų faktorių, svarbių apsaugą prieš denatūraciją duoda tam tikrą apsaugą bet rezultatai varijuoja išeigos yra nedidelės, pareiškėjas pateikė naujus priedus, kurių mišiniai su sorbitu padidina jų stabilizuojančią galią.Including the fact that sorbitol prior to thermal denaturation, plasma shortages between plasma samples cannot be achieved, the proposed composition, this factor, important anti-denaturation protection affords some protection but results varying in yield, the Applicant has provided new additives containing mixtures with sorbitol increases their stabilizing power.

Taigi, pagal šj, išradimą siūlomą kompoziciją sudaro sorbitas, kalcio chloridas, heparinas ir lizinas. Įvairių komponentų koncentracijos reguliuojamos tokiu būdu, kad plazmoje, skirtoje pasterizavimui, būtų sekančios galutinės koncentracijos:Thus, the composition of the present invention comprises sorbitol, calcium chloride, heparin and lysine. The concentrations of the various components are adjusted to give the following final plasma concentrations for pasteurisation:

- 50-80% sorbito, tinkamiausia 60%,- 50-80% sorbitol, preferably 60%,

- 0.1-1% vienetų/ml heparino, tinkamiausia 0.5 vienetų/ml,- 0.1 to 1% units / ml heparin, preferably 0.5 units / ml,

- 1-10 g/1 lizino, tinkamiausia 4 g/1,- 1-10 g / l lysine, preferably 4 g / l,

- 3-5 mM CaCl2, tinkamiausia 4 mM.- 3-5 mM CaCl 2 , most preferably 4 mM.

Sutinkamai su išradimu, kompozicija yra dedama j, šviežią plazmą, j, užšaldytą-atšildytą šviežią plazmą arba Į plazmą, iš kurios pašalinti krionuosėdų pavidalu proteinai prieš tai, kai pastaroji pasterizuojama prie 60°C ± 1°C 10 vai.According to the invention, the composition is added to fresh plasma, frozen-thawed fresh plasma or plasma deprotected proteins before the latter is pasteurized at 60 ° C ± 1 ° C for 10 hours.

Pasibaigus pasterizavimui, temperatūra palaipsniui sumažinama iki 20°C, ir tirpalas yra dializuojamas, kad pašalintų sorbitą ir hepariną. Dializės buferio tirpalo pH yra 7, jis turi 4-10 mM natrio citrato, 4 mM kalcio chlorido, 0.13 M natrio chlorido ir 4 g/1 lizino.After pasteurization, the temperature is gradually lowered to 20 ° C and the solution is dialyzed to remove sorbitol and heparin. The dialysis buffer has a pH of 7 and contains 4-10 mM sodium citrate, 4 mM calcium chloride, 0.13 M sodium chloride and 4 g / l lysine.

Priklausomai nuo poreikio, dializės buferiai gali turėti j, vairias sudėtis. Po to tirpalas yra koncentruojamas, kad atstatyti plazmos proteinų fiziologinę normą. Gautas tirpalas steriliai filtruojamas, kondicionuojamas, po to užšaldomas ar liofilinamas.Depending on the need, dialysis buffers may have a variety of compositions. The solution is then concentrated to restore the physiological normalization of plasma proteins. The resulting solution is sterile filtered, conditioned, then frozen or lyophilized.

Išradimas taip pat apima plazmos pasterizavimo būdą, kurį sudaro kompozicijos, sutinkamai su išradimu, pridėjimas į plazmą, prieš ją kaitinant, ir po to pasterizuotos plazmos dializė prieš anksčiau nustatytą buferio tirpalą.The invention also encompasses a method of pasteurizing plasma comprising adding the compositions according to the invention to plasma prior to heating and then dialyzing the pasteurized plasma against a pre-determined buffer solution.

Šis būdas vertingas ypač tuo, kad jį galima taikyti didelėms plazmos partijoms, gaunamoms iš keleto individualių donorų. Dar daugiau, partijų nuo 100 iki 200 1 ar daugiau pasterizavimas įgalina po atitinkamų testų garantuoti partijų kokybės pastovumą.This technique is particularly valuable because it can be applied to large batches of plasma from several individual donors. Moreover, pasteurisation of batches of 100 to 200 batches of 1 or more enables the batch quality to be guaranteed after appropriate tests.

Iš kitos pusės plazmos partijos, pasterizuotos kaip pateikta išradime, gali būti naudojamos kaip pakaitalai pacientams, turintiems krešėjimo faktorių, tokių kaip V faktoriaus, XI faktoriaus ir XIII faktoriaus, kuriems nėra valytų koncentratų, nepakankamumą.On the other hand, plasma batches pasteurized as provided in the invention can be used as substitutes in patients with deficiency of coagulation factors such as factor V, factor XI and factor XIII in the absence of purified concentrates.

Tokiu būdu, išradimas apima taip pat pasterizuotus plazmos tirpalus, gautus sutinkamai su išradimu, ir ypač skirtus, iš vienos pusės, V, XI ir XIII faktorių nepakankamumui gydyti, iš kitos pusės - pakaitalų terapijai, reikalaujančiai visos plazmos arba krionusodinto supernatanto.Thus, the invention also encompasses pasteurized plasma solutions obtained in accordance with the invention and, in particular, for the treatment of factor V, XI and XIII deficiency on the one hand and replacement therapy requiring whole plasma or cryoprecipitated supernatant on the other.

Sekantis pavyzdys aprašo išradimo įgyvendinimo variantą, neapribojant jo apimties.The following example illustrates an embodiment of the invention without limiting its scope.

PAVYZDYS:EXAMPLE:

Į du litrus atšildytos plazmos pridedama heparino (1000 vienetų), lizino (8 g) ir kalcio chlorido (220 mg). Šie du produktai pridedami druskų miltelių pavidale, plazma atsargiai maišoma. Po to palaipsniui dedama 120 g neištirpinto sorbito.Two liters of thawed plasma are added with heparin (1000 units), lysine (8 g) and calcium chloride (220 mg). These two products are added in the form of a salt powder, and the plasma is mixed gently. Then 120 g of undissolved sorbitol are added gradually.

Pasterizavimas atliekamas 5 1 tūrio inde kaitinant 60°C temperatūroje 10 vai. vandens vonioje arba termostatuojamame rezervuare. Po pasterizavimo sorbitas ir heparinas pašalinami dializuojant dirbtiniu inkstu arba ultrafiltracijos sistema, kaip PellikonM sistema su kasetėmis, naudojant citratinį buferinį tirpalą, turintį 4 g/1 lizino, 4 mM CaCl2 ir 0,13 M NaCl. Dializę gali lydėti koncentravimas tokia pat sistema, kad pasiektų krešėjimo faktorių kiekį apytiksliai iki 1 vieneto/ml, kas rodo gerą terapinę plazmos kokybę. Plazma dializuojama prie 370 mosmol/ltr osmosinio slėgio ir pH 7. Produktas tada steriliai filtruojamas, pav., naudojant Millipack” 40 filtrą (Millipore), turintį 0.22 ųm dydžio poras. Produktas yra paskirstomas į plastikinius maišelius užšaldymui arba į medicininius flakonus liofilinimui.The pasteurisation is carried out by heating in a 5 liter vessel at 60 ° C for 10 hours. water bath or thermostatically controlled tank. After pasteurisation, sorbitol and heparin are removed by dialysis with an artificial kidney or ultrafiltration system, such as a Pellikon M system with cartridges, using citrate buffer containing 4 g / l lysine, 4 mM CaCl 2 and 0.13 M NaCl. Dialysis may be accompanied by concentration in the same system to achieve coagulation factor levels of approximately 1 unit / ml, which indicates good therapeutic plasma quality. Plasma is dialyzed at an osmotic pressure of 370 mosmol / ltr and pH 7. The product is then sterile filtered using, for example, a Millipack 40 filter (Millipore) having a pore size of 0.22 µm. The product is distributed in plastic bags for freezing or in medical vials for lyophilization.

Plazmos stabilizavimas pasterizuojant ir ultrafiltruoj ant, pridėjus kalcio chlorido, heparino ir lizino, įgalina gauti sekančias išeigas, lyginant su kontroliniu pavyzdžiu, turinčiu tik liziną ir sorbitą.Plasma stabilization by pasteurization and ultrafiltration on addition of calcium chloride, heparin and lysine allows the following yields to be obtained compared to a control sample containing lysine and sorbitol only.

FVIIIc FVIIIc 87% 87% prieš against 66% 66% FVc FVc 77% 77% prieš against 35% 35% FVIIc FVIIc 55% 55% prieš against 52% 52% FIXc FIXc 60% 60% prieš against 49% 49% Koaguliuoj anti fibrinogenas Anti-fibrinogen is coagulated 81% 81% prieš against 57% 57% FXIII FXIII 77% 77% prieš against 71% 71%

Nebuvo pastebėta krešėjimo faktorių aktyvacijos požymių, naudojant šį kalcio chlorido kiekį. Tokiu būdu, santykis jaučio FVII/koagulianto FVII yra 0.95 prieš 1.09 kontroliniame pavyzdyje. Stabilumas, tirtas FVIII aktyvumo atžvilgiu, 24 vai. konservavus produktą skystame būvyje prie kambario temperatūros, nepablogėjo, palyginus su kontroliniu pavyzdžiu (atsistatėNo signs of coagulation factor activation were observed with this amount of calcium chloride. Thus, the ratio of bull FVII / coagulant FVII is 0.95 versus 1.09 in the control. Stability tested for FVIII activity, 24 hours. after preserving the liquid product at room temperature did not deteriorate compared to the control sample (

100% aktyvumo). Tai patvirtina procentinis kiekis PKA < 2% pasterizuotiems produktams ir kontroliniams pavyzdžiams.100% activity). This is confirmed by the percentage PKA <2% for pasteurized products and controls.

Be to, bandymai su žiurkėmis, gavusiomis intraveniniu būdu tokiu metodu pasterizuotą plazmą, rodo, jog nestebima hipotenzinio efekto ir nesukeliama jokių pokyčių širdies ritme.In addition, studies in rats given intravenous pasteurized plasma show no hypotensive effect or cardiac change.

Claims (15)

IŠRADIMO APIBRĖŽTISDEFINITION OF INVENTION 1. Kompozicija kraujo plazmai stabilizuoti pasterizavimo metu, besiskirianti tuo, kad ją sudaro sorbito, heparino, kalcio chlorido ir lizino mišinys.A composition for stabilizing blood plasma during pasteurisation, characterized in that it comprises a mixture of sorbitol, heparin, calcium chloride and lysine. 2. Kompozicija pagal 1 punktą, besiskiriant i tuo, kad sorbito koncentracija yra tarp 500 ir 800 g/1.Composition according to claim 1, characterized in that the concentration of sorbitol is between 500 and 800 g / l. 3. Kompozicija pagal 2 punktą, besiskiriant i tuo, kad sorbito koncentracija yra 600 g/1.Composition according to claim 2, characterized in that the sorbitol concentration is 600 g / l. 4. Kompozicija pagal vieną iš 1-3 punktų, besiskirianti tuo, kad heparino koncentracija yra tarp 100 ir 1000 vienetų/1.Composition according to one of Claims 1 to 3, characterized in that the concentration of heparin is between 100 and 1000 units / l. 5. Kompozicija pagal 4 punktą, besiskiriant i tuo, kad heparino koncentracija yra 500 vienetų/1.5. The composition of claim 4, wherein the heparin concentration is 500 units / L. 6. Kompozicija pagal vieną iš 1-5 punktų, besiskirianti tuo, kad kalcio chlorido koncentracija yra tarp 3 ir 5 mM.6. A composition according to any one of claims 1-5, wherein the concentration of calcium chloride is between 3 and 5 mM. 7. Kompozicija pagal 6 punktą, besiskiriant i tuo, kad kalcio chlorido koncentracija yra 4 mM.7. The composition of claim 6, wherein the concentration of calcium chloride is 4 mM. 8. Kompozicija pagal vieną iš 1-7 punktų, besiskirianti tuo, kad lizino koncentracija yra tarp 1 ir 10 g/1.8. A composition according to any one of claims 1-7, wherein the concentration of lysine is between 1 and 10 g / l. 9. Kompozicija pagal 8 punktą, besiskiriant i tuo, kad lizino koncentracija yra 4 g/1.9. The composition of claim 8, wherein the lysine concentration is 4 g / L. 10. Būdas kraujo plazmai pasterizuoti, besiskiriantis tuo, kad prieš terminį apdorojimą i plazmą deda kompoziciją pagal vieną iš 1-9 punktų ir po to ją pašalina dializuojant.10. A process for pasteurizing a blood plasma comprising adding a composition according to any one of claims 1-9 to the plasma prior to heat treatment and then removing it by dialysis. 11. Būdas pagal 10 punktą, besiskiriantis tuo, kad dializę atlieka prie pH 7 buferio tirpalu, turinčiu 4-10 mM natrio citrato, 4 mM kalcio chlorido, 0.13 M natrio chlorido ir 4 g/1 lizino.11. The method of claim 10, wherein the dialysis is performed at pH 7 in a buffer containing 4-10 mM sodium citrate, 4 mM calcium chloride, 0.13 M sodium chloride, and 4 g / l lysine. 12. Būdas pagal 10 arba 11 punktą, besiskiriantis tuo, kad jis tinka plazmos tūriams nuo 1 iki keleto šimtų litrų.12. A method according to claim 10 or 11, characterized in that it is suitable for plasma volumes of 1 to several hundred liters. 13. Plazmos tirpalas terapiniam naudojimui, skirtas kraujo krešėjimo V, XI ir XIII faktorių nepakankamumui kompensuoti, besiskiriantis tuo, kad jis yra gautas, naudojant būdą pagal vieną iš 10-12 punktų.Plasma solution for therapeutic use, for use in the preparation of a method according to any one of claims 10 to 12 for the compensation of deficiencies in blood coagulation factors V, XI and XIII. 14. Visa plazma terapiniam naudojimui, besiskirianti tuo, kad ją pasterizuoja naudojant būdą pagal vieną iš 10-12 punktų.14. All plasma for therapeutic use, characterized in that it is pasteurized by a method according to one of claims 10 to 12. 15. Krionusodintos ir atskirtos nuo krioproteinų plazmos supernatantas terapiniam naudojimui, besiskiriantis tuo, kad jį pasterizuoja naudojant būdą pagal vieną iš 10-12 punktų.15. Cryoprecipitated and separated cryoprotein plasma supernatant for therapeutic use, characterized in that it is pasteurized by a method according to one of claims 10 to 12.
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DE4240103A1 (en) * 1992-05-26 1993-12-02 Behringwerke Ag Process for inactivating viruses in protein preparations
DE19508192A1 (en) * 1995-03-09 1996-09-12 Behringwerke Ag Stable transglutaminase preparations and process for their preparation
US20060019234A1 (en) * 2004-07-22 2006-01-26 Shanbrom Technologies, Llc Modern blood banking employing improved cell preservation composition
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2916711A1 (en) 1979-04-25 1980-11-06 Behringwerke Ag Blood coagulation factors and process for their manufacture
EP0035204A2 (en) 1980-03-05 1981-09-09 Miles Inc. Pasteurized therapeutically active protein compositions

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3045153A1 (en) * 1980-11-29 1982-07-08 Behringwerke Ag, 3550 Marburg METHOD FOR THE PRODUCTION OF BLOOD COagulation FACTORS AND THE PREPARATION OF FACTORS IX AND X THEREFORE PRODUCED
DE3336631A1 (en) * 1983-10-08 1985-04-18 Behringwerke Ag, 3550 Marburg METHOD FOR THE PASTEURIZATION OF PLASMA OR CONCENTRATES OF THE BLOOD COAGINING FACTORS II, VII, IX AND X
US4543210A (en) * 1984-10-04 1985-09-24 Miles Laboratories, Inc. Process for producing a high purity antihemophilic factor concentrate
DK18288D0 (en) * 1988-01-15 1988-01-15 Nordisk Gentofte PROCEDURE FOR PASTEURIZATION OF Aqueous SOLUTIONS OF FACTOR VIII

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2916711A1 (en) 1979-04-25 1980-11-06 Behringwerke Ag Blood coagulation factors and process for their manufacture
EP0035204A2 (en) 1980-03-05 1981-09-09 Miles Inc. Pasteurized therapeutically active protein compositions

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EDWARD TABOR ET AL.: "Inactivation of hepatitis B virus by heat in antithrombin III stabilized with citrate", TROMBOSIS RESEARCH, 1981, pages 233 - 238
RICHMAN CM, ROWLEY JD.: "Correlation of in vitro culture pattern and Q-banded karyotype in acute nonlymphocytic leukemia", AM J HEMATOL., 1983, pages 37 - 47

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