WO2003094953A1 - Transporteur d'oxygene selectionne parmi l'hemoglobine, la myoglobine et des derives de celles-ci pour le traitement d'un trouble fonctionnel organique/d'une lesion tissulaire resultant d'une insuffisance aigue d'apports - Google Patents

Transporteur d'oxygene selectionne parmi l'hemoglobine, la myoglobine et des derives de celles-ci pour le traitement d'un trouble fonctionnel organique/d'une lesion tissulaire resultant d'une insuffisance aigue d'apports Download PDF

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Publication number
WO2003094953A1
WO2003094953A1 PCT/EP2003/003911 EP0303911W WO03094953A1 WO 2003094953 A1 WO2003094953 A1 WO 2003094953A1 EP 0303911 W EP0303911 W EP 0303911W WO 03094953 A1 WO03094953 A1 WO 03094953A1
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Prior art keywords
oxygen
use according
hemoglobin
lack
acute
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PCT/EP2003/003911
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German (de)
English (en)
Inventor
Wolfgang Barnikol
Harald Pötzschke
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Sanguibiotech Gmbh
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Priority to AU2003226812A priority Critical patent/AU2003226812A1/en
Publication of WO2003094953A1 publication Critical patent/WO2003094953A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/41—Porphyrin- or corrin-ring-containing peptides
    • A61K38/42—Haemoglobins; Myoglobins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents

Definitions

  • the present invention relates to the use of one or more natural or modified oxygen carriers or derivatives thereof, for the preparation of an agent, for the treatment of an organ dysfunction due to an acute lack of supply and for the treatment / prevention of tissue damage as a result of such a disorder.
  • acute oxygen and / or nutrient deficiency states such as tinnitus, heart attack, stroke, sudden hearing loss, dizziness, placenta insufficiency, kidney shock or lung shock can be treated according to the invention.
  • the oxygen carrier (s) can be of human or animal origin and are used as aqueous solutions which, for example, have the naturally present electrolyte concentration or also further salts / additives.
  • the oxygen carrier is used in a concentration of 2 to 200 g / liter solution, preferably 10 to 80 g / liter over a period of 1 day (e.g. single dose) up to 6 weeks with multiple doses depending on the need and indication.
  • Oxygen carriers and artificial oxygen carriers produced by modification of natural oxygen carriers such as hemoglobin or myoglobin for supplying oxygen to a living organism have been known for a long time, cf. DE 197 01 37, EP 97 100790, DE 44 18 937, DE 38 41 105, DE 37 14 351, DE 35 76 651.
  • the hemoglobins or myoglobins are obtained in a known manner and can are crosslinked, resulting in crosslinked (intramolecular), polymeric and in particular hyperpolymeric products.
  • the natural oxygen carriers which can optionally also be crosslinked beforehand, can also be covalently linked to polyalkylene oxides, cf. Harris JM, Poly (Ethylene Glycol) Chemistry: Biotechnical and Biorrredfeal Applications, Plenum, New York, 1992).
  • DE-A1 100 31 740 (WO 02/00230), DE-A1 100 31 744 and DE-A1 100 31 742.1 describe modified oxygen carriers or special processes for their preparation which are crosslinked, polymerized and with polyalkylene oxides are implemented.
  • the carriers thus produced are considered suitable, particularly for intravascular or biomedical use, e.g. as a replacement for the blood, described as an addition to this, since such oxygen carriers have, among other things, particularly good plasma tolerance.
  • an application in the case of a chronic oxygen deficiency condition is also described here in general, but without specifying the type / location and amount or duration of such an application.
  • EP-A 0 857 733 describes that artificial oxygen carriers are used to supply living systems particularly when the oxygen binding sites have been previously provided with a protective ligand such as carbon monoxide. This ligand is not removed before use, but while it is working. This is to ensure that the function of the oxygen carrier is released gradually, i.e. gradually, depending on the respective requirements, and that an undesired temporary oversupply of oxygen is avoided when used on a patient (see column 5, paragraph 2 in EP-A 857 733).
  • the use of the protective ligament Kohte ⁇ rrr ⁇ xrd has the advantage that oxidation of the carrier can be prevented, but, as mentioned, a rapid or possibly desired temporal oversupply with oxygen is not possible, since carbon monoxide is very firmly ligated to the oxygen binding sites and is released slowly.
  • Acute shortages of an organ and consequent malfunctions with the result of a possible tissue damage can have different causes. These include e.g. B. nutrient deficiency situations, or acute lack of oxygen e.g. due to stress, acute vasoconstriction or also due to chronic deficiency such as chronic vasoconstriction. It is known that nutrient therapy can be used for tinnitus diseases or Meniere's syndrome. Here, hyperlipoproteinemia is specifically used to improve the ear diseases mentioned.
  • the oxygen carrier or carriers are selected from hemoglobin, myoglobin or derivatives thereof. Accordingly, they are natural or preferably crosslinked, polymerized and / or pegylated, i.e. covalently linked with a polyalkylene oxide. Particularly preferred oxygen carriers are those which are both crosslinked, polymerized (intermolecularly crosslinked) and in particular also pegylated.
  • the oxygen carriers can be of human or animal origin.
  • the oxygen carriers mentioned it was found that by means of the oxygen carriers mentioned, immediate treatment of the organ in a deficient state with sufficient amounts of de-energized oxygen, namely bioavailable oxygen, is possible, whereby toxification and also tissue damage can be avoided or treated. This is ensured in particular by the reversible binding to the carrier.
  • the oxygen carrier is in particular as an infusion over a required period of z. B. 1 day to several days one or more times, possibly up to several weeks, until the acute deficiency has been remedied insofar as the organ concerned is again working properly. Administration may also continue thereafter, depending on the condition and conditions of the situation, to achieve a final cure.
  • oxygen carrier can be used directly, for example in physiological sodium chloride solution or in other aqueous solutions as described below.
  • the oxygen carrier is preferably crosslinked with a crosslinker, polymerized.
  • the oxygen carrier which can be hemoglobin or myoglobin or mixtures thereof, preferably hemoglobin or also hemoglobin-myoglobin mixtures, can also be covalently linked to a polyalkylene oxide which is selected from polyethylene oxide, polypropylene oxide, or a copolymer of ethylene oxide and propylene oxide or a Esters, ethers or ester amides thereof.
  • Oxygen carriers which are linked to a polyethylene oxide or a suitable derivative thereof are particularly preferably used.
  • the covalently attached polyalkylene oxide has a molar mass of 200 to 5000 g / mol.
  • the carrier or carriers are very particularly preferably crosslinked, polymerized and covalently linked (pegylated) with a polyalkylene oxide, as described in DE-A1 100 31 740 (WO 02/00230), DE-A1 100 31 744 and DE-A1 100 31 742.1.
  • the oxygen carriers can optionally also be carbonylated.
  • Particularly suitable oxygen carriers are hemoglobins or hemoglobins modified as described above with a molecular weight of 65,000 to, in particular from 70,000 to 15,000,000 g / mol, in particular 90,000 to 15,000,000, those with a molecular weight of 300,000 to 15,000 000, especially 300,000 to 10,000,000, in particular from 700,000 to 10,000,000, preferably 700,000 to 5,000,000 g / mol, are particularly preferred, or also myoglobins or modified derivatives thereof with a molecular weight of 15,000 g / Mol to 5,000,000 g / mol, preferably 100,000 to 3,000,000 or also 200,000 to 3,000,000 or mixtures of hemoglobin and myoglobin oxygen carriers as indicated.
  • the ratio of hemoglobin to myoglobin oxygen carrier or derivatives thereof can be from 20: 1 to 1:20, in particular 10: 1 to 1:10.
  • the ratio of natural to modified oxygen carrier can be 20.1 to 1:20, especially 10.1 to 1.10.
  • the oxygen carrier (s) used according to the invention are effective when a concentration of 0.2 to 20% by weight, in particular 1 to 18% by weight, especially 3 to 15, preferably 3 to 12% by weight, in particular 5 to 10% by weight is present in the medium intended for the treatment. Accordingly, 2 to 200 g / liter or 10 to 180 g or 30 to 150 or 120 g or 50 to 100 g / liter of oxygen carriers are present in the medium.
  • the medium is especially water.
  • the oxygen carriers, in particular the artificial derivatives, of the type described can be produced as described in the abovementioned prior art, which is incorporated here. Particularly preferred are those which are produced as described in DE-A 100 31 740 (WO 02/00230), DE-A 100 31 742 and DE-A 100 31 744. For this purpose, moderately high molecular weight polyalkylene oxides are covalently bound to the hemoglobin or myoglobin molecules crosslinked with a crosslinker. Details of the process for the production of such artificial oxygen carriers are described above (e.g. in DE-A100 31 740), incorporated therein as indicated and can be summarized as follows:
  • Suitable as hemoglobin (or myoglobin) starting material for the production of the oxygen carriers used according to the invention is monomeric, native or with certain effectors, e.g. B. the oxygen affinity of hemoglobin (myoglobin) such as pyridoxal-5'-phosphate or 2-nor-2-formyl-pyridoxal-5'-phosphate, chemically converted and modified myoglobin or hemoglobin from humans, pigs or cattle. Human and in particular swine hemoglobin is preferred.
  • the hemoglobin or myoglobin may optionally be deoxygenated by carbonylation before use.
  • crosslinking of monomeric, native or effector-linked hemoglobin or myoglobin with a number of crosslinkers is known and has been described many times in the literature, cf. the above German applications.
  • examples include: divinyl sulfone, epichlorohydrin, butadiene diepoxide, hexamethylene diisocyanate, the dialdehydes glyoxal and glutardialdehyde and the diimido esters dimethyl suberimidate, dimethylmalonimidate and dimethyl adipimidate.
  • dialdehydes for example malondialdehyde, succindialdehyde, glutardialdehyde, adipindialdehyde and suberdialdehyde, and glyoxal
  • dialdehydes for example malondialdehyde, succindialdehyde, glutardialdehyde, adipindialdehyde and suberdialdehyde, and glyoxal
  • structurally more complex compounds which occur through oxidative ring opening of the cyclic half-acetal and half-ketal structures of the sugar molecules in monosaccharides and oligosaccharides and oligosaccharides and oligosaccharides, are also known which are produced by reaction with the dialdehydes o-adenosine and o-ATP, formed by ring-opening oxidation of the ribose in adenosine and in adenosine triphosphate.
  • Different molecular weights can be obtained, cf. EP 0 201 618.
  • molar ratios of the crosslinking agent used - in particular the bifunctional crosslinking agent - of 3 to 60 times, preferably 6 to 35 times are used.
  • glutaraldehyde a 7- to 10-fold molar excess of the glutaraldehyde is preferably used.
  • Chemically unstable linkages, especially the Schiff bases, which arise in the reaction of functional aldehyde groups with amino groups of the hemoglobins, are reductively known in a known manner by reaction with suitable reducing agents, such as.
  • Bifunctional crosslinking agents are preferably selected for crosslinking the hemoglobins / myoglobins, for example butanedie epoxide, divinyl sulfone, a diisocyanate, in particular hexamethylene diisocyanate, cyclohexyl diisocyanate and 2,5-bisisocyanatobenzenesulfonic acid, a di-N-hydroxysuccinimidyl ester, a dialido ester, or a diimido ester, or a diimido ester, or a dialido ester, or a dialido ester, or a dialido ester, or a dialido ester, or a dialido ester, or a diimido ester, or a diimido ester, or a diimido ester, or a diimido ester, or a dialido ester, or a dialido este
  • the reaction with the polyalkylene oxide which in itself, but in particular additionally, ie before or after or ' during the crosslinking, is likewise described in the above-mentioned German applications and incorporated therein. It is essentially reacted with a polyalkylene oxide or a derivative thereof, such as polyethylene oxide, polypropylene oxide, or copolymers of ethylene oxide and propylene oxide.
  • the polyalkylene oxide derivative is particularly preferably an ether, an ester, or an ester amide with a short-chain aliphatic organic radical.
  • the covalently attached polyalkylene oxide preferably has a molar mass between 200 and 5000 g / mol, preferably between 500 and 2000 g / mol.
  • the number of attached polyalkylene oxides in the product used according to the invention is between 1 and 40, in particular 4 to 15, molecules of polyalkylene oxide per molecule of the hemoglobin monomer.
  • the polyalkylene oxide can first be covalently linked and only then can the crosslinking be as described.
  • a covalent attachment of a polyalkylene oxide can also be done both before the Networking, as well as after the networking. With these alternatives, processing and further processing can also be carried out unchanged as described.
  • Oxygen carriers which have been produced are particularly preferably used according to the invention in that highly purified hemoglobin or also myoglobin i) is first deoxygenated; ii) is then covalently reacted with an oxygen binding effector; iii) the solution is then mixed with a non-chemically reactive effector; and then iv) the hemoglobin with glutardialdehyde is stably covalently crosslinked with one another in an inverse concentration gradient reaction, based on the concentration of the crosslinking agent and the hemoglobin to be crosslinked, then the solution is diluted with water, and then v) a polyethylene oxide covalently tied up vi) the product obtained is worked up in a known manner.
  • Crosslinking with glutardialdehyde is very particularly preferred.
  • the oxygen carrier (s) can be oxygenated in a known manner before the use according to the invention.
  • the optionally derivatized oxygen carrier used according to the invention is derived from cattle, pork or human hemoglobin. Pig hemoglobin is particularly preferred because of its structural and functional similarity. In addition, human hemoglobin is also preferred.
  • the oxygen carrier can also be myoglobin or the product thereof modified as described above or mixtures thereof with hemoglobin derivatives. Pig hemoglobin, in particular human hemoglobin, is preferred.
  • an immediate improvement in the deficiency state is surprisingly achieved by a currently sufficient but non-toxic amount of oxygen.
  • a further improvement in the deficiency state can be achieved by adding further suitable additives such as salts, glucose, insulin, one or more natural amino acids or mixtures suitable for the patient to be treated.
  • the aqueous-based media can contain suitable additives, in particular 0 to 20% by volume, preferably 0.01 to 20% by weight, in particular 0.1 to 20% by weight and especially 0.1 to 15% , These are preferably selected from glucose, natural amino acids for the respective application, that is to say the amino acids natural for humans or animals, insulin, each in a physiological concentration or multiples thereof for the application in question, and also suitable known antibiotics, tissue factors and natural and / or artificial buffer substances such as TRIS, bicarbonate, phosphate and physiologically tolerable salts such as sodium chloride, potassium chloride, calcium magnesium chloride, sodium citrate, sodium lactate, likewise in a suitable, in particular physiological concentration or multiples thereof, or mixtures thereof, for the respective application.
  • suitable additives in particular 0 to 20% by volume, preferably 0.01 to 20% by weight, in particular 0.1 to 20% by weight and especially 0.1 to 15% , These are preferably selected from glucose, natural amino acids for the respective application, that is to say the amino acids natural for humans or animals, insulin, each in
  • Glucose can be, for example, in amounts of 0.1 to 5% by weight, insulin in physiological dosage or in amounts of up to 25 IU / ml, the natural amino acids known for the respective application, that is to say those known for humans or for the respective animals Amino acids e.g. B. 0 or 0.01 up to 5 wt.%, Or tissue factors such as interleukins are present in physiological amounts up to 10 times the amount thereof. Particularly preferred additives are physiological sodium chloride solution (0.8 to 1.5%), in particular 0.9%). Glucose (in amounts as stated above, preferably for example 1%) and insulin in physiological dosage, if appropriate up to 5 times thereof, and also mixtures thereof. Above all, potassium chloride, magnesium chloride, sodium bicarbonate or mixtures thereof can also be added or additionally added in the amounts indicated above.
  • the oxygen carrier or carriers used according to the invention are effective over a wide pH range, namely from 5.5 to 9, in particular 6.5 to 8.
  • a pH of 7.4 can be present in the medium administered, such as the infusion.
  • infusions are used especially during the acute phase of the event.
  • the oxygen carriers are particularly preferably administered in an amount of 10 to 80 g / liter, in particular 12 to 50 g / liter (infusion) medium, so that an average oxygen partial pressure of approximately 30 mm Hg is present in the tissue during administration, which does not increase is high in order to cause an oxidative, harmful oversupply, but is sufficient to remedy the acute deficiency state.
  • Pig hemoglobin in a concentration of 330 g / L dissolved in an aqueous electrolyte of the composition 50 mM NaHCO 3 and 100 rriM NaCl, was deoxygenated at 4 ° C. by stirring the solution under constantly renewed, pure nitrogen over the solution. Then 4 mol sodium ascorbate (as a 1 molar solution in water) per mol (monomeric) hemoglobin was added and allowed to react for 6 hours. The solution was titrated to a pH of 7.1 with 0.5 molar lactic acid, 1.1 mol of pyridoxal-5'-phosphate per mol of hemoglobin were added and the mixture was allowed to react for 16 h.
  • the synthesis of the human hemoglobin crosslinked with glutardialdehyde was carried out as in Example 2, but using concentrated human hemoglobin and using a 16-fold molar excess of the crosslinking agent.
  • Polymers were obtained by fractionating the solution of the crosslinking products with the aid of preparative volume exclusion chromatography (according to EP-A 95 10 72 80.0: “Process for the production of uniform molecular hyperpolymeric hemoglobins” with Sephacryl S-300 HR gel, Pharmacia Biotech, Freiburg, D ) (here as the first eluted 57 mass% of the cross-linked hemoglobin).
  • the cross-linked hemoglobins were divided into two parts A and B.
  • Cross-linked bovine hemoglobin was produced by cross-linking concentrated bovine hemoglobin with a 14-fold molar excess of glutardialdehyde according to Example 2, a molecular fractionation of the synthesis products, the binding of mPEG-SPA-1000 according to Examples 2 and 3.
  • Figure 5 shows a molecular weight distribution of the unmodified hemoglobin polymer, namely an eluogram of a volume exclusion chromatography (on the gel “Sephacryl S-400 HR”, Pharmacia Biotech, Freiburg, D), the modal value of the molecular weight distribution here is 810 kg / mol ,
  • Example 2 12% of an unmodified human hemoglobin as described in Example 1 and 6% by weight of a modified product as described in Example 2 were dissolved in 100 ml of purified water containing 0.9% by weight of sodium chloride, 0.2% by weight of sodium bicarbonate, 1% by weight % Glucose given. The solution is immediately ready for use.
  • Example 10 The same treatment as in Example 10 was carried out in a female patient aged 65 years. Again, there was no increase in the level of transaminase and no sign of an immune reaction.

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Abstract

La présente invention concerne l'utilisation d'au moins un transporteur d'oxygène naturel ou modifié ou de dérivés de tels transporteurs d'oxygène pour la production d'un agent destiné au traitement d'un trouble fonctionnel organique résultant d'une insuffisance aiguë d'apports et au traitement/à la prévention d'une lésion tissulaire résultant d'un tel trouble. Avec cet agent on peut en particulier traiter des états pathologiques résultant d'une insuffisance aiguë d'apports d'oxygène et/ou de produits nutritifs, tels que le tinnitus, l'infarctus cardiaque, l'apoplexie, la surdité soudaine, les vertiges, l'insuffisance placentaire, les chocs d'origine rénale et les chocs d'origine pulmonaire. Le ou les transporteur(s) d'oxygène peuvent être d'origine humaine ou animale et être utilisés sous forme de solutions aqueuses qui, par exemple, présentent la concentration d'électrolyte existant naturellement ou bien également d'autres sels/additifs. Le transporteur d'oxygène est utilisé en solution à une concentration de 2 à 200 g/litre, de préférence de 10 à 80 g/litre, sur une période d'un jour (par exemple en une seule administration) à 6 semaines, en plusieurs administrations, selon les besoins et les prescriptions.
PCT/EP2003/003911 2002-05-11 2003-04-15 Transporteur d'oxygene selectionne parmi l'hemoglobine, la myoglobine et des derives de celles-ci pour le traitement d'un trouble fonctionnel organique/d'une lesion tissulaire resultant d'une insuffisance aigue d'apports WO2003094953A1 (fr)

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AU2003226812A AU2003226812A1 (en) 2002-05-11 2003-04-15 Oxygen carrier, selected from haemoglobin, myoglobin and their derivatives, for treating organ dysfunction/tissue damage caused by an acute supply deficiency

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DE10220992A DE10220992A1 (de) 2002-05-11 2002-05-11 Verwendung eines oder mehrerer Sauerstoffträger, ausgewählt aus Hämoglobin, Myoglobin und Derivaten hiervon zur Behandlung einer Organfunktionsstörung infolge eines akuten Versorgungsmangels und zur Behandlung/Vermeidung einer Gewebeschädigung infolge einer solchen Störung
DE10220992.8 2002-05-11

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005046717A1 (fr) * 2003-11-12 2005-05-26 Sanguibio Tech Gmbh Utilisation d'hemoglobine hyperpolymere pour traiter un oedeme pulmonaire
WO2015032672A1 (fr) * 2013-09-03 2015-03-12 Sanguibiotech Gmbh Préparations pour une meilleure oxygénation des tissus par respiration péritonéale
US10821158B2 (en) 2013-03-15 2020-11-03 William Schindler Polyalkylene oxide valerate hemoglobin conjugates

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997035883A1 (fr) * 1996-03-28 1997-10-02 Northfield Laboratories, Inc. Procede et appareil destines a la preparation d'un substitut acellulaire des erythrocytes
US5854210A (en) * 1995-04-10 1998-12-29 Baxter International Inc. Use of cross-linked hemoglobin in treating subarachnoid hemorrhage
US6046161A (en) * 1992-01-30 2000-04-04 Baxter International, Inc. Use of hemoglobin in the treatment of cardiogenic shock
US6054427A (en) * 1997-02-28 2000-04-25 The Regents Of The University Of California Methods and compositions for optimization of oxygen transport by cell-free systems
DE10031742A1 (de) * 2000-06-29 2002-01-17 Sanguibio Tech Ag Verfahren zur Herstellung künstlicher Sauerstoffträger aus kovalent vernetzten Hämoglobinen mit verbesserten funktionellen Eigenschaften durch Vernetzung in Anwesenheit chemisch nicht reagierender Effektoren der Sauerstoffaffinität der Hämoglobine

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10031744A1 (de) * 2000-06-29 2002-01-17 Sanguibio Tech Ag Mit Blutplasma verträgliche, vernetzte und mit Polyalkylenoxiden konjugierte Säugetierhämoglobine als künstliche medizinische Sauerstoffträger, ihre Herstellung und ihre Verwendung
DE10031740A1 (de) * 2000-06-29 2002-02-14 Sanguibio Tech Ag Künstliche Sauerstoffträger aus vernetztem modifizierten Human- oder Schweinehämoglobin mit verbesserten Eigenschaften, Verfahren zu ihrer technisch einfachen Herstellung aus gereinigtem Material in hohen Ausbeuten, sowie deren Verwendung

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6046161A (en) * 1992-01-30 2000-04-04 Baxter International, Inc. Use of hemoglobin in the treatment of cardiogenic shock
US5854210A (en) * 1995-04-10 1998-12-29 Baxter International Inc. Use of cross-linked hemoglobin in treating subarachnoid hemorrhage
WO1997035883A1 (fr) * 1996-03-28 1997-10-02 Northfield Laboratories, Inc. Procede et appareil destines a la preparation d'un substitut acellulaire des erythrocytes
US6054427A (en) * 1997-02-28 2000-04-25 The Regents Of The University Of California Methods and compositions for optimization of oxygen transport by cell-free systems
DE10031742A1 (de) * 2000-06-29 2002-01-17 Sanguibio Tech Ag Verfahren zur Herstellung künstlicher Sauerstoffträger aus kovalent vernetzten Hämoglobinen mit verbesserten funktionellen Eigenschaften durch Vernetzung in Anwesenheit chemisch nicht reagierender Effektoren der Sauerstoffaffinität der Hämoglobine

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005046717A1 (fr) * 2003-11-12 2005-05-26 Sanguibio Tech Gmbh Utilisation d'hemoglobine hyperpolymere pour traiter un oedeme pulmonaire
US7598220B2 (en) 2003-11-12 2009-10-06 Sanguibio Tech Gmbh Use of hyperpolymeric hemoglobin for the treatment of pulmonary edema
US10821158B2 (en) 2013-03-15 2020-11-03 William Schindler Polyalkylene oxide valerate hemoglobin conjugates
WO2015032672A1 (fr) * 2013-09-03 2015-03-12 Sanguibiotech Gmbh Préparations pour une meilleure oxygénation des tissus par respiration péritonéale
US10646507B2 (en) 2013-09-03 2020-05-12 Sangui Biotech International, Inc. Compositions for improved tissue oxygenation by peritoneal ventilation

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