CS261814B1 - Agent for heparine removing from blood in vitro - Google Patents

Agent for heparine removing from blood in vitro Download PDF

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CS261814B1
CS261814B1 CS871443A CS144387A CS261814B1 CS 261814 B1 CS261814 B1 CS 261814B1 CS 871443 A CS871443 A CS 871443A CS 144387 A CS144387 A CS 144387A CS 261814 B1 CS261814 B1 CS 261814B1
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cellulose
cross
propyl
starch
linked starch
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CS871443A
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Czech (cs)
Slovak (sk)
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CS144387A1 (en
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Miroslav Prom Chem Csc Antal
Rudolf Ing Csc Toman
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Miroslav Prom Chem Csc Antal
Toman Rudolf
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Priority to CS871443A priority Critical patent/CS261814B1/en
Priority to DK115688A priority patent/DK115688A/en
Priority to HU104188A priority patent/HU203411B/en
Priority to EP88103275A priority patent/EP0281128A1/en
Publication of CS144387A1 publication Critical patent/CS144387A1/en
Publication of CS261814B1 publication Critical patent/CS261814B1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2400/00—Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
    • G01N2400/10—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • G01N2400/38—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence, e.g. gluco- or galactomannans, e.g. Konjac gum, Locust bean gum, Guar gum
    • G01N2400/40—Glycosaminoglycans, i.e. GAG or mucopolysaccharides, e.g. chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, heparan sulfate, and related sulfated polysaccharides

Abstract

A method and a preparation for the separation of heparin from blood or blood plasma in vitro is described. The preparation contains at least one blood-insoluble starch and/or cellulose derivative having tertiary or quaternary amino groups with a preferred exchange capacity of 0.3 to 1.3 mmol/g bound thereto. Particularly advantageous derivatives are imidazolium-N.N'-diyl-bis(2-hydroxy-3-propyl)cellulose ether chloride and imidazolium-N,N'-diyl-bis(2-hydroxy-3-propyl)ether chloride of crosslinked starch. The preparation, which is preferably present in tablet form, contains up to 12 parts by weight of microcrystalline cellulose per part by weight of the starch or cellulose derivative. The starch or cellulose derivative preferably has a particle size of 50 to 300 mu m, but it is also possible to use derivatives of smaller or larger particle size. The preparation can be used in medicine and in particular in haematology for the determination of the real haemostatic potential, and everywhere that a simple and rapid separation of heparin from blood and blood plasma is required in vitro.

Description

Riešenie sa týika přípravku na odstraňovanie heparínu z krvi in vitro. Podstata (přípravku spočívá v tom, že pozostáva z aspoň jedného v krvi nerozpustného derivátu ipolysaciharidu s naviazanými terciárnymi alebo kvartérnymi amínoskupinami s výměnnou kapacitou 0,3 až 1,3 mmól. g_1. Prípravok, s výhodou vo formě tablety, obsahuje až 1'2 hmot, dielov mikrokryštalickej celulózy, vztiahnuté na 1 hmot, diel derivátu polysacharidu. Derivát polysacharidu sú s výhodou deriváty celulózy alebo deriváty škrobu. Derivát polysacharidu pozostáva z častíc o velkosti 50 až 300 μΐη, avšak je možné použiť i derivát polysacharidu s menším alebo váčším rozmerom. Prípravok na odstraňovanie iheparínu z ikrvi má použitie v medicíně, najma hematológii, při vyšetřovaní pacientov užívajúcich heparín na reálny hemostatický potenciál. Ďalej všade tam, kde sa vyžaduje jednoduchý a rýchly spůsob odstránenia heparínu z krvi in vitro.The solution relates to a preparation for removing heparin from blood in vitro. The composition consists of at least one blood-insoluble derivative of ipolysaccharide with attached tertiary or quaternary amino groups having an exchange capacity of 0.3 to 1.3 mmol. G -1 . The preparation, preferably in the form of a tablet, contains up to 1 ' 2 parts by weight of microcrystalline cellulose, based on 1 part by weight, of the polysaccharide derivative The polysaccharide derivative is preferably a cellulose derivative or a starch derivative The polysaccharide derivative consists of particles having a particle size of 50 to 300 μ avšakη, but a polysaccharide derivative with The preparation for the removal of iheparin from the blood is used in medicine, especially hematology, in the examination of patients taking heparin for real haemostatic potential, and wherever a simple and rapid method of removing heparin from the blood in vitro is required.

Vynález sa týká přípravku na odstraňovanie heparínu z krvi, najmě z krvnej plazmy in vitro.The invention relates to a preparation for the removal of heparin from blood, in particular from blood plasma in vitro.

-Heparín sa často aplikuje paclentom trpiacim trombo-embolickými onemocneniami, alebo při róznych typoch operácií. 0spěšnost, resp. neúspěšnost' liečby iheparínom sa overuje komplexnými hemokoagulačnými testami, ako sú Quickov- test, iparciálny tromboplastínový čas plazmy, rekalcifbkačný a trombínový čas plazmy.-Heparin is often administered to patients suffering from thromboembolic diseases or to various types of surgery. 0success, respectively. the failure of iheparin treatment is verified by complex haemocoagulation tests such as the Quick test, the plasma partial thromboplastin time, the plasma recalcification and thrombin time.

Uvedené -testy sa robia in vitro a aby sa pomooou nich zistil reálny hemost-atický potenciál, musíme aplikovaný heparín z odobratej vzorky krvnej plazmy odstániť. Bežne sa heparín neutralizuje reakciou s protamíinom [J. G. Allen a kol.: J. Lab. Clin. Med. 34, 473 (1949); H. A. Perkins -a kol.: J. Lab. Clin. Med. 48, 223 (1956)], avšak titrácia je otázna, nakolko v odobratých vzorkách krvnej 'plazmy pacientoiv sa nevie přesná hladina heparínu.These tests are carried out in vitro and, in order to determine the real haemostathic potential, we must remove the applied heparin from the collected blood plasma sample. Normally, heparin is neutralized by reaction with protamine [J. G. Allen et al., J. Lab. Clin. Med. 34, 473 (1949); Perkins, H. A., et al., J. Lab. Clin. Med. 48, 223 (1956)], but titration is questionable since the exact levels of heparin are not known in the patient's blood plasma samples taken.

To znamená, že prebytok protamínu v plazme zostáva často nedetegovaný, rovnako aj nezneutralizovaný heparín. To spósobuje, že výsledky hemokoagulačných testov sú značné nepřesné. Na túto skutočnosť už upozornil J. S. Wright a kol. [J. Cardiovas. Surg. 5, 244 (1964) ].This means that excess protamine in plasma often remains undetected as well as unneutralized heparin. This causes the results of hemocoagulation tests to be significantly inaccurate. This has already been pointed out by J. S. Wright et al. [J. Cardiovasc. Surg. 5, 244 (1964)].

S cielOm vyhnúť sa hoře uvedeným ned-ostatkom použili Thompson a kol. [J. Lab. Clin. Med. 88, 922 (1976)] kolónovú chromatografiu na odstránenie heparínu a protamínu zo vzoriek krvnej plazmy.In order to avoid the above mentioned disadvantages, Thompson et al. [J. Lab. Clin. Med. 88, 922 (1976)] column chromatography to remove heparin and protamine from blood plasma samples.

ECTEOLA — celulózu použili na zachytenie až 300 jednotiek heparínu z 1 ml plazmy a na karboxymetyl celulóze sa adsorboval pro-tamín. Použitie iónomeničov před komplexnými hemoikoagulačnými testami plazmy je však prácne a časovo velmi náročné. Zároveň najmenej 1 ml plazmy sa zachytí na stlpcoch iónomeničov, čo je vážným nedostatkom při pediatrických případech, kde možno získat pre testovanie len malé množstva plazmy. Z tohoto dóvodu je stále velmi aktuálna příprava takého preparátu, ktorý by umožnil rýchle a jednoduché cdstránenie heparínu z vyšetrovanej krvi, resp. krvnej plazmy bez vedlajších negativných účinkov při následných komplexných hemokoagulačných testoch.ECTEOLA-cellulose was used to capture up to 300 units of heparin from 1 ml of plasma and protamine was adsorbed on carboxymethyl cellulose. However, the use of ion exchangers prior to complex plasma hemoicoagulation tests is laborious and time consuming. At the same time, at least 1 ml of plasma is captured on ion exchange columns, a serious drawback in pediatric cases where only small amounts of plasma can be obtained for testing. For this reason, the preparation of such a preparation which would allow rapid and simple removal of heparin from the blood being examined, respectively, is still very topical. blood plasma without negative side effects in subsequent complex haemocoagulation tests.

Podstata přípravku na odstraňovanie heparínu z ikrvi, najma z krvnej plazmy in vitro spočívá- v tom, že pozostáva z aspoň jedného v krvi nerozpustného derivátu polysacharidu s naviazanými terciárnymi alebo kvartérnymi amínoskupinami s výměnnou kapacitou 0,3 až 1,3 mmól. g_1. Prípravok, s výhodou vo formě tablety, obsahuje až 12 hmot, dielov mikrokryštalickej celulózy vztiahnuté na 1 hmot, diel derivátu polysacharidu. Deriváty polysacharidu sú s výhodou deriváty celulózy alebo deriváty škrobu.The essence of the preparation for removing heparin from blood, in particular from blood plasma in vitro, consists of at least one blood-insoluble derivative of a polysaccharide with attached tertiary or quaternary amino groups having a capacity of exchange of 0.3 to 1.3 mmol. g _1 . The composition, preferably in the form of a tablet, contains up to 12 parts by weight of microcrystalline cellulose based on 1 part by weight of the polysaccharide derivative. The polysaccharide derivatives are preferably cellulose derivatives or starch derivatives.

Derivát celulózy je vybratý zo skupiny: dietylamínoetyl celulóza, dimetyl-amínoetyl celulóza, trimetylamóniumetyl celulóza, dietylamínopropyl celulóza, trietylamóniumpropyl celulóza, dimetylamínopropyl celulóza, trimetylamóniumpropyl celulóza, dietylamíno-2-hydroxypropyl celulóza, polyetylénimín celulóza, trietylamónium-2-hydroxyproipyl celulóza, dimetylamíno-2-hydroxypropyl celulóza, celulóza sietovaná zmesou epichlórhydrínu a dietylamínu v alkalickom prostředí, imidazólio-N,N‘-diyl-bis- (2-hydroxy-3-propyl)-ový éter celulózy, chlorid dimetylamíno-bis-(2-.hydroxy-3-propyl)-ový éter celulózy, benzyldimetylamónium-2-hydroxypropyl celulóza.The cellulose derivative is selected from the group: diethylaminoethyl cellulose, dimethylamino amino cellulose, trimethylammonium ethyl cellulose, diethylaminopropyl cellulose, triethylammonium propyl cellulose, dimethylaminopropyl propyl cellulose, dimethylammonium propyl cellulose, diethylamino-2-hydroxypropyl cellulose, polyethylamine-2-hydroxypropyl cellulose, triethylaminopropyl cellulose, hydroxypropyl cellulose, cellulose crosslinked with a mixture of epichlorohydrin and diethylamine in an alkaline medium, imidazolyl-N, N'-diyl-bis- (2-hydroxy-3-propyl) -cellulose ether, dimethylamino-bis- (2-hydroxy- 3-propyl) cellulose ether, benzyldimethylammonium-2-hydroxypropyl cellulose.

Derivát škrobu je vybratý zo skupiny:The starch derivative is selected from:

dietylamínoetyl sieťovaný škrob, dimetylamínoetyl sieťovaný šikrob, trimetylamóniumetyl sieťovaný škrob, dietylamínopropyl sieťovaný škrob, trietylamóniumpropyl sieťovaný škrob, dimetylamínoipropyl sieťovaný škrob, trimetylamóniumpropyl sieťovaný škrob, dietylamíno-2-hydroxypropyl sieťovaný škrob, polyetylénimín sieťovaný škrob, trietylamónlum-2-hydroxypropyl sieťovaný škrob, dimetylamíno-2-hydroxypropyl sieťovaný škrob, škrob sieťovaný zmesou epichlórhydrínu a dietylamínu v -alkalickom prostředí, imidazólio-N,N‘-diyl-bis- (2-hydroxy-3-propyl)-ový éter sieťovaného škrobu, chlorid dimetylamíno-bis- (2-hydroxy-3-propyl)-ový éter sieťovaného škrobu, benzyldimetylamónium-2-hydroxyproipyl sieťovaný škrob.diethylaminoethyl crosslinked starch, dimethylaminoethyl crosslinked starch, trimethylammonium ethyl crosslinked starch, diethylaminopropyl crosslinked starch, triethylammoniumpropyl crosslinked starch, dimethylaminoethylpropyl crosslinked starch, trimethylammoniumpropyl crosslinked starch, diethylamino-2-hydroxypropyl crosslinked starch, polyethylaminoethylpropyl crosslinked starch, 2-hydroxypropyl cross-linked starch, starch cross-linked with a mixture of epichlorohydrin and diethylamine in an alkaline medium, imidazolio-N, N'-diyl-bis- (2-hydroxy-3-propyl) -crosslinked starch ether, dimethylamino-bis- (2-hydroxypropyl) ether -hydroxy-3-propyl) cross-linked starch ether, benzyldimethylammonium-2-hydroxyproipyl cross-linked starch.

Derivát polysacharidu pozostáva z častíc o velikosti 50 až 300 μΐη, avšak je možné použit i derivát polysacharidu s menším alebo věčším rozmerom.The polysaccharide derivative consists of particles having a size of 50 to 300 μΐη, but a smaller or larger polysaccharide derivative may also be used.

Výhodou navrhovaného přípravku je, že sa získá jednoduchým, ekonomicky výhodným spósobom a je vhodný na rýchle -odstránenie heparínu z vyšetrovanej krvi alebo krvnej plazmy bez vedlajších negativných účinkov při následných hemokoagulačných testoch.The advantage of the proposed preparation is that it is obtained in a simple, economically advantageous manner and is suitable for the rapid removal of heparin from the blood or blood plasma to be examined, without the adverse effects of subsequent haemocoagulation tests.

Příklad 1Example 1

Chlorid imidazólio-N,N‘-diyl-bis- (2-hydroxy-3-propyl)-ový éter celulózy (20 g, zrnitosť 50 až 300 ^um) s výměnnou kapacitou 0,7 mmól. g1 sa dokonale premieša s mik281814 rokryštalickou celulózou pře farmaceutické použitie (60 g, 50 až 300 μΐη). Získaná zmes s dobrými takovými vlastnosťami sa tabletuje n.a tabletky s hmotnosťou 80 mg a pevnosťou 3 až 4 kg. Každá tabletka obsahuje 20 mg chlorid lmidazólio-N,N‘-diyl-bis-(2-hydroxy-3-propyl j-ového éteru celulózy a 60 mg mikrokryštalickej celulózy.Cellulose imidazolium-N, N'-diyl-bis- (2-hydroxy-3-propyl) ether (20 g, particle size 50-300 µm) with a capacity of 0.7 mmole. g 1 is thoroughly mixed with mik281814 rocrystalline cellulose for pharmaceutical use (60 g, 50 to 300 μΐη). The obtained mixture with good such properties is tableted to tablets having a weight of 80 mg and a strength of 3-4 kg. Each tablet contains 20 mg of limidazolium-N, N'-diyl-bis- (2-hydroxy-3-propyl) -cellulose ether and 60 mg of microcrystalline cellulose.

P r í к 1 a d '2Example 1 a d '2

Chlorid imidazólio-N,N‘-diyl-bis-(2-bydroxy-3-propyl)-ový éter celulózy (50 g, 50 až 300 μΐη), s výměnnou kapacitou 1,3 mmól. . g_1 sa dokonale premieša s mikrokryštalickou celulózou pre farmaceutické použitie (600 g). Tabletováním sa získájú tabletky s hmotnosťou 65 mg a pevnosťou 3 až 4 kg. Každá tabletka obsahuje 5 mg chlorid imidazólio-N,N‘-diyl-bis-( 2-hydroxy-3-propyl ] -ového éteru celulózy a 60 mg mikrokryštalíckej celulózy.Cellulose imidazolium-N, N'-diyl-bis- (2-dihydroxy-3-propyl) ether (50 g, 50 to 300 μΐη), with a capacity of exchange of 1,3 mmole. . g- 1 is intimately mixed with microcrystalline cellulose for pharmaceutical use (600 g). Tableting yields tablets having a weight of 65 mg and a strength of 3-4 kg. Each tablet contains 5 mg of imidazolium-N, N'-diyl-bis- (2-hydroxy-3-propyl) -cellulose ether and 60 mg of microcrystalline cellulose.

Příklad 3Example 3

Chlorid lmidazólio-N,N‘-diyl-bis-(2-hydroxy-3-propyl)-óvý éter mikrokryštalickej celulózy (600 g], s výměnnou kapacitou 0,3 mmól. g_1 sa tabletuje. Tabletováním sa získajú tabletky s hmotnosťou 120' mg a pevnosťou 4 až 5 kg. Každá tabletka obsahuje 120 mg chlorid imidazólio-N,N‘-diyl-bis-(2-hydroxy-3-propyl)-ového éteru celulózy.Lmidazólio chloride-N, N-diyl-bis- (2-hydroxy-3-propyl) ether -óvý microcrystalline cellulose (600 g], the exchange capacity of 0.3 mmol. G _1 is tabletted. Tableting to give tablets of a weight of 120 mg and a strength of 4-5 kg Each tablet contains 120 mg of imidazolium-N, N'-diyl-bis- (2-hydroxy-3-propyl) -cellulose chloride.

Příklad 4Example 4

Postupuje sa ako v příklade 1, s tým rozdielom, že sa ako derivát celulózy použije dietylamínoetyl celulóza.The procedure is as in Example 1 except that diethylaminoethyl cellulose is used as the cellulose derivative.

Příklad 5Example 5

Postupuje sa ako v příklade 2, s tým rozdielom, že sa ako derivát celulózy použije trimetylamónlumetyl celulóza.The procedure is as in Example 2, except that trimethylammonlumethyl cellulose is used as the cellulose derivative.

Příklad 6Example 6

Postupuje sa ako v příklade 1, s tým rozdielom, že sa ako derivát celulózy použije dietylamíno-2-hydroxypropyl celulóza.The procedure is as in Example 1 except that diethylamino-2-hydroxypropyl cellulose is used as the cellulose derivative.

P r í к 1 a d 7Example 1 a d 7

Postupuje sa ako v příklade 2, s tým rozdielom, že sa ako derivát celulózy použije celulóza modifikovaná zmesou epichlórhydrínu a dletylamínu v alkalíckom prostředí.The procedure is as in Example 2, except that cellulose modified with a mixture of epichlorohydrin and dlethylamine in an alkaline medium is used as the cellulose derivative.

Příklad 8Example 8

Postupuje sa ako v příklade 3, s tým rozdielom, že sa ako derivát celulózy použije polyetylénimín celulózy.The procedure is as in Example 3, except that the cellulose derivative used is polyethyleneimine cellulose.

Příklad 9Example 9

Postupuje sa ako v příklade 1, s tým rozdielom, že sa ako derivát celulózy použije dimetylamínoetyl celulóza.The procedure is as in Example 1 except that dimethylaminoethyl cellulose is used as the cellulose derivative.

Příklad 10Example 10

Postupuje sa ako v příklade 2, s tým rozdielom, že sa ako derivát celulózy použije trietylamónium-2-hydroxypropyl celulóza.The procedure is as in Example 2, except that triethylammonium-2-hydroxypropyl cellulose is used as the cellulose derivative.

Příklad 11Example 11

Postupuje sa ako' v příklade 3, s tým rozdielom, že sa ako derivát celulózy použije trimetylamóniumpropyl celulóza.The procedure is as in Example 3, except that trimethylammonium propyl cellulose is used as the cellulose derivative.

Příklad 12Example 12

Postupuje sa ako v příklade 1, s tým rozdielom, že sa ako derivát celulózy použije chlorid dimetylamíno-bis-(2-hydroxy-3-propylj-ový éter celulózy.The procedure is as in Example 1, except that the cellulose derivative used is cellulose chloride dimethylamino-bis- (2-hydroxy-3-propyl) ether.

Příklad 13Example 13

Postupuje sa ako v příklade 3, s tým rozdielom, že sa ako derivát celulózy použije benzyldimetylamónium-2-hydrOxyprcpyl celulóza.The procedure is as in Example 3, except that benzyldimethylammonium-2-hydroxypropyl cellulose is used as the cellulose derivative.

Příklad 14Example 14

Postupuje sa ako v příklade 1, s tým rozdielom, že sa použije zmes chlorid imidazólio-N,N‘-d.iyl-bis-(2-hydroxy-3-propyl]-ového' éteru celulózy (10 g) a chlorid imidazólio-N,N‘-diyl-bis-(2-hydroxy-3-propyl j-ového éteru sieťovaného škrobu (10 g), s výměnnou kapacitou 0,7 mmól. g_1 a táto sa dokonale premieša s mikrokryštalickou celulózou pre farmaceutické použitie (60 g, 50 až 300 дт).The procedure was as in Example 1 except that a mixture of imidazolium-N, N'-dimethyl-bis- (2-hydroxy-3-propyl) cellulose ether (10 g) and imidazolium chloride was used. N, N-diyl-bis- (2-hydroxy-3-propyl-j the AC ether cross-linked starch (10 g), the exchange capacity of 0.7 mmol. g 1 and the latter is intimately mixed with microcrystalline cellulose for pharmaceutical use (60 g, 50 to 300 days).

Příklad 15Example 15

Postupuje sa ako v příklade 1, s tým rozdielom, že sa použije zmes dietylamínoetyl celulóza (10 g) a dicíylamínohydroxypropyl celulóza (10 g), s výměnnou kapacitou 0,7 mmól. g_1 a táto sa dokonale premieša s mikrokryštalickou celulózou pre farmaceutické použitie (60 g, 50 až 300 μηι).The procedure was as in Example 1, except that a mixture of diethylaminoethyl cellulose (10 g) and di-amino amino hydroxypropyl cellulose (10 g) was used, with a exchange capacity of 0.7 mmol. g- 1 and this is intimately mixed with microcrystalline cellulose for pharmaceutical use (60 g, 50 to 300 μηι).

Příklad 16Example 16

Postupuje sa ako v příklade 1, s tým rozdielom, že sa použije zmes trimetylamóniumpropyl sletovaný škrob (10 g) a dietylamínoetyl sieťovaný škrob (10 gj, s výměnnou kapacitou 0,7 mmól. g_1 a táto sa dokonale premieša s mikrokryštalickou celulózou pre farmaceutické použitie (60 g, 50 až 300 <um).The procedure is as in Example 1 except that a mixture of trimetylamóniumpropyl soldering starch (10 g), and cross-linked starch diethylaminoethyl (10 gj, the exchange capacity of 0.7 mmol. G 1 and the latter is intimately mixed with microcrystalline cellulose for pharmaceutical use (60 g, 50-300 µm).

Příklad 17Example 17

К 0,5 až 2 ml krvnej plazmy v skúmavke (12 X 90 mm) sa přidá tableta -a nechá napučať 1 až 3 min. pri 20 °C. Potom sa obsah skúmavky intenzívně zamieša na vibrátore až kým sa tabletová substancia rovnoměrně rozloží v plazme a mieša sa ďalej na miešadle 10 min. pri 20 °C. Tabletová substancia s adsorbovaným heparínom sa odstředí na laboratorně] centrifúge (1 200 (, 5 min.) a příslušné alikvóty plazmy sa použijú na hemokoagulačné testy.A tablet is added to 0.5 to 2 ml of blood plasma in a tube (12 X 90 mm) and allowed to swell for 1 to 3 minutes. at 20 ° C. Then, vigorously mix the contents of the tube on a vibrator until the tablet substance is evenly distributed in the plasma and mix further on the mixer for 10 min. at 20 ° C. The heparin-adsorbed tablet substance is centrifuged in a laboratory centrifuge (1200 (, 5 min)) and appropriate plasma aliquots are used for hemocoagulation assays.

Jedna tableta stačí na adsorpciu heparínu do koncentrácie 10 NIHJ/ml. V případe vyšších koncentrácií heparínu sa použije vláčej tabliet.One tablet is sufficient to adsorb heparin to a concentration of 10 NIHJ / ml. For higher heparin concentrations, trainer tablets are used.

Vynález má použitie v medicíně, najma hematologii, pri vyšetřovaní pacientov užívajúcich heparín, na reálny hemostatický potenciál. Ďalej všade tam, kde sa vyžaduje jednoduchý a rýchly spósob odstránenia heparínu z krvi in vitro.The invention has utility in medicine, particularly hematology, in the examination of patients receiving heparin for real hemostatic potential. Furthermore, wherever a simple and rapid method of removing heparin from blood in vitro is required.

Claims (7)

PREDMET VYNÁLEZUOBJECT OF THE INVENTION 1. Prípravok na odstraňovanie heparínu z ikrvi, najma z krvnej plazmy in vitro, vyznačujúci sa tým, že pozostáva z aspoň jediného v krvi nerozpustného derivátu polysacharidu s naviazanými terciárnymi alebo kvartérnymi amínoskupinami s výměnnou kapacitou 0,3 až 1,3 mmól. g1.A preparation for the removal of heparin from blood, in particular from an in vitro blood plasma, comprising at least one blood-insoluble derivative of a polysaccharide with attached tertiary or quaternary amino groups having an exchange capacity of 0.3 to 1.3 mmol. g 1 . 2. Prípravok, s výhodou vo formě tablety, podTa bodu 1, vyznačujúci sa tým’ že obsahuje až 12 hmot, dielov mikrokryštalickej celulózy vztiahnuté na 1 hmot, diel derivátu polysacharidu.2. A composition, preferably in the form of a tablet according to claim 1, comprising up to 12 parts by weight of microcrystalline cellulose based on 1 part by weight of the polysaccharide derivative. 3. Prípravok podTa bodov 1 a 2, vyznačujúci sa tým, že derivát polysacharidu sú s výhodou deriváty celulózy alebo deriváty škrobu.3. The composition according to claim 1, wherein the polysaccharide derivative is preferably a cellulose derivative or a starch derivative. 4. Prípravok, podTa bodov 1 až 3, vyznačujúci sa tým, že derivát celulózy je vybratý zo skupiny:4. The composition of claims 1 to 3, wherein the cellulose derivative is selected from the group consisting of: dietylamínoetyl celulóza, dimetylamínoetyl celulóza, trimetylamóniumetyl celulóza, dietylamínopropyl celulóza, trietylamóniumpropyl celulóza, dimetylamínopropyl celulóza, trimetylamóniumpropyl celulóza, dietylamíno-2-hydroxypropyl celulóza, polyetylénimín celulóza, trietylamónium-2-hydroxypropyl celulóza, dimetylamíno-2-hydroxypropyl celulóza, celulóza sietovaná zmeso-u epichlórhydrínu a dietylamínu v alkalickom prostředí, imidazólio-N,Nť-diyl-bis- (2-hydroxy-3-propyl)-ový éter celulózy, chlorid dimetylamíno-bis-(2-hydroxy-3-propyl)-ový éter celulózy, benzyldimetylamónium-2-hydroxypropyl celulóza.diethylaminoethyl cellulose, dimethylaminoethyl cellulose, trimethylammonium methyl cellulose, diethylaminopropyl cellulose, triethylammonium propyl cellulose, dimethylaminopropyl cellulose, trimethylammonium propyl cellulose, diethylamino-2-hydroxypropyl cellulose, polyethyleneimine cellulose, triethylammonium cellulose, triethylammonium cellulose, triethylammonium cellulose, triethylammonium cellulose, epichlorohydrin and diethylamine in a basic medium, imidazoline-N, ent-diyl-bis (2-hydroxy-3-propyl) -ový cellulose ether, chloride, dimethylamino-bis- (2-hydroxy-3-propyl) ether of cellulose -ový , benzyldimethylammonium-2-hydroxypropyl cellulose. 5.Prípravok, podlá bodov 1 až 3, vyznačujúci sa tým, že derivát škrobu je vybratý o skupiny:5. The preparation of claims 1 to 3, wherein the starch derivative is selected from the following groups: dietylamínoetyl, sieťovaný škrob, dimetylamínoetyl sieťovaný škrob, trimetylamóniumetyl sieťovaný škrob, dietylamínopropyl sieťovaný škrob, trietylamóniumpropyl sieťovaný škrob, dimetylamínopropyl sieťovaný škrob, trimetylamóniumpropyl sieťovaný škrob, dietylamíno-2-hydroxypro-pyl sieťovaný škrob, polyetylénimín sieťovaný škrob, trietylamónium-2-hydroxypropyl sieťovaný škrob, dimetylamíno-2-hydroxypropyl sieťovaný škrob, škrob sieťovaný zmesou epichlórhydrínu a dietylamínu v alkalickom prostředí, imidazólio-N,N‘-diyl-bis- (2-hydroxy-3-propyl)-ový éter sieťovaného škrobu, chlorid dimetylamíno-bis- (2-hydroxy-3-propyl)-ový éter sletovaného· škrobu, benzyldimetylamónium-2-hydroxypropyl sieťovaný škrob.diethylaminoethyl, cross-linked starch, dimethylaminoethyl cross-linked starch, trimethylammonium ethyl cross-linked starch, diethylaminopropyl cross-linked starch, triethylammonium propyl cross-linked starch, dimethylammonium propyl cross-linked starch, diethylamino-2-hydroxypropyl-cross-linked starch, polyethylene cross-linked starch, polyethylene cross-linked starch, , dimethylamino-2-hydroxypropyl cross-linked starch, starch cross-linked with a mixture of epichlorohydrin and diethylamine in an alkaline medium, imidazolium-N, N'-diyl-bis- (2-hydroxy-3-propyl) cross-linked starch ether, dimethylamino-bis- (2-hydroxy-3-propyl) ether of cross-linked starch, benzyldimethylammonium-2-hydroxypropyl cross-linked starch. ‘6. Testovací prípravok, podTa bodov 1 až 5, vyznačujúci sa tým, že derivát polysacharidu pozostáva z častíc o velkosti 50 až 300 mikrometrov.'Sixth Test composition according to Claims 1 to 5, characterized in that the polysaccharide derivative consists of particles having a size of 50 to 300 microns. Severografia, n. p. závodSeverography, n. p. the race 7, Most7, Most
CS871443A 1987-03-04 1987-03-04 Agent for heparine removing from blood in vitro CS261814B1 (en)

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CS871443A CS261814B1 (en) 1987-03-04 1987-03-04 Agent for heparine removing from blood in vitro
DK115688A DK115688A (en) 1987-03-04 1988-03-03 PREPARATION FOR THE REMOVAL OF HEPARIN FROM BLOOD IN VITRO
HU104188A HU203411B (en) 1987-03-04 1988-03-03 Composition for in vitro removal of heparin from blood
EP88103275A EP0281128A1 (en) 1987-03-04 1988-03-03 Method and preparation for the separation of heparin from blood in vitro

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US5151192A (en) * 1990-07-13 1992-09-29 Pall Corporation Method for removing heparin from blood or plasma
GB9202019D0 (en) * 1992-01-30 1992-03-18 Imperial College Methods and apparatus for assay of sulphated polysaccharides
US6197289B1 (en) 1997-07-01 2001-03-06 Terumo Cardiovascular Systems Corporation Removal of biologically active agents
FR2872063B1 (en) * 2004-06-29 2009-02-27 Rhodia Cons Spec Ltd USE OF POSSIBLY MODIFIED AND POSSIBLY INSOLUBLE STARCH FOR THE REMOVAL OF NATURAL ORGANIC MATERIALS IN LIQUIDS

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US4226599A (en) * 1979-06-20 1980-10-07 Warner-Lambert Company Removal of heparin from heparin-containing blood plasma samples using a triethylaminoethyl cellulose tablet
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