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WO2002087540A1 - Artificial blood made of hemoglobin encapsulated in liposomes - Google Patents

Artificial blood made of hemoglobin encapsulated in liposomes Download PDF

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Publication number
WO2002087540A1
WO2002087540A1 PCT/HU2002/000030 HU0200030W WO02087540A1 WO 2002087540 A1 WO2002087540 A1 WO 2002087540A1 HU 0200030 W HU0200030 W HU 0200030W WO 02087540 A1 WO02087540 A1 WO 02087540A1
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WO
WIPO (PCT)
Prior art keywords
blood
haemoglobin
process according
particles
lipoid
Prior art date
Application number
PCT/HU2002/000030
Other languages
French (fr)
Inventor
István HORVÁTH
Original Assignee
Horvath Istvan
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Horvath Istvan filed Critical Horvath Istvan
Publication of WO2002087540A1 publication Critical patent/WO2002087540A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/795—Porphyrin- or corrin-ring-containing peptides
    • C07K14/805—Haemoglobins; Myoglobins

Definitions

  • the subject of the invention relates to a process for producing artificial blood, using haemoglobin lyophilized or obtained from fresh blood, suitable for supplying blood temporarily for an organism of any blood group drained of blood.
  • Artificial blood is capable of substituting one of the functions of blood linked with the red blood cells, the transport of gases. It may help patient through biological ashpyxia arising due to shortage of blood. At the same time it makes up fluid deficiency in the organism, ensuring recovery of osmotic value of cells, and also provides possibility for the haematogens to restore the original composition of blood under physiological blood pressure and circulation conditions with as little delay as possible. If loss of blood is of such an extent, that urgent supply of other blood components (proteins, enzymes etc.) besides electrolytes is also required, then after supplying the artificial blood the possibility of the intake of genuine blood under hospital conditions of the patient can be ensured as well.
  • other blood components proteins, enzymes etc.
  • said artificial blood contains haemoglobin locked into a lipoid shell in form of particles that can be suspended in a watery substance, and said particles are suitable or can be made suitable for supplying blood for all vertebrata, the set aim can be achieved.
  • the invention relates to a process for producing artificial blood, using haemoglobin lyophilized or obtained from fresh blood, characterized by that said artificial blood contains haemoglobin locked into a lipoid shell in form of particles that can be suspended in a watery substance, and said particles are suitable or can be made suitable for supplying blood for all vertebrata.
  • the size of the particles should remain below the size of the red-blood cells or red-blood corpuscles characteristic of the given species and said particles permeate through the tubes of the capillaries owing to their size.
  • haemoglobin used derives directly from haemoglobin solution produced from blood or it is haemoglobin dried by lyophilization. From the point of view of application of artificial blood the haemoglobin advantageously is of congener type or derives from other vertebrata.
  • the material of the lipoid membrane covering the haemoglobin is built by one or more lipoid component.
  • forming of the lipoid membrane takes place from starting from the lipoid or from the lipoid solvents and at a temperature higher than the melting point of the lipoids starting from the liquid lipoids.
  • the producing of the lipoid membrane takes place advantageously on solid, fluid surface or in gaseous substance.
  • the formation of the particles splitting of the membrane into particle size advantageously takes place under the influence of physical energy.
  • a preferable application of the artificial blood produced during the process according to the invention is, that the haemoglobin will not be washed away from the particles even after longer storage of under proper conditions.
  • the artificial blood produced during the process according to the invention is stored either in liquid form or in lyophilized form, the powder suspended in the proper solution provides artificial blood of full value.
  • Haemoglobin must be enveloped into a semi-permeable lipoid membrane to retain its capability for supplying oxygen and carbon dioxide. During the process the haemoglobin is put between two monomolecular lipoid membranes of properly arranged structure and liposomes are formed by splitting planparallel membranes. The other possibility is to put the haemoglobin on a monomolecular membrane and the membrane is splitted in a way, that the pieces of the membrane roll up the haemoglobin on their surface, similarly as cigarette paper covers tobacco. By packaging into the membrane it can be achieved, that the haemoglobin should not be dissolved during circulation, because dissolved haemoglobin is secreted in the kidneys.
  • Overriding principle for the use of artificial blood is, that haemoglobin is closed into a liposome in such a way, that artificial blood should not have allergic influence. This requirement can be fulfilled so, that lipoids existing in the organism are used for forming the membrane substituting the cell membrane of the 'cells'of the artificial blood. Primarily those materials are used, which show the least variability during evolution.
  • This solution has double benefits.
  • the artificial blood produced is suitable not only for substitution and temporary supply of the blood of one race, namely the human, but the same blood can be used for the substitution, temporary supply of blood of almost any warm-blooded animal.
  • the advantage of the theoretical and practical solution is, that the beneficial effect observed on one species of animals can be transferred even without modification to the other species.
  • the human species, the Homo sapiens have the greatest benefit of all this, because every figure of the experimental results can be taken as of the same value of observations on humans beings.
  • the complex containing haemoglobin may assume allergen characteristics in case the artificial 'cell membrane' acting as allergen or antigen is capable of stimulating anti-bodies damaging the organism in some way. This possibility must be taken into consideration even if lipoid molecules used by us do not usually appear as antigens or allergens.
  • allergens usually appear as antigens or allergens.
  • material earlier not considered allergen by allergologists in fact act as allergens.
  • a liposome can be produced with applying material with the least immunological power which can match the features of those of the natural cells or corpuscles produced in the organism.
  • the basic material of the membrane liposome of the artificial blood produced by us is compiled exclusively of lipoids that can be found during evolution in each family of the warm-blooded animals. It has no extraneous element, and no allergic effect in animal tests could be noticed. On basis of our achievements it seems realistic to achieve the set aim, i.e.our preparation will prove to be suitable for filling the function of blood as supplier of oxygen and carbon dioxide in all organisms drained of blood irrespective of blood group. As mentioned in the introduction, it is first of all suitable for meeting the demands of casualties and operations lasting for a relatively short time, but in a certain limited circle it ensures solution of medical treatment as well. On basis of the results of the animal tests carried out so far we find it suitable for use for human beings as well keeping in mind the theoretical considerations.
  • a melt or solution of the lipoid is produced at a proper temperature, which is suitable for making a thin monomolecular layer on a smooth surface.
  • the surface of the body, the temperature, the flowing speed of the solution or that of the lipoid melt should be optimum.
  • the smooth surface can include dents of maximum 400 nm.
  • the temperature can differ from the melting temperature by maximum 10% in case of certain lipoids. (obviously to the higher range).
  • the flowing speed of lipoid can be 1 mg/sec/50 cm2 +-10% on a surface of a proper angle.
  • the physical impacts consistent with the viscosity of the lipoid can range between electromagnetic waves (270 nm) of advantageously applicable frequency and energy through sound-waves of proper wavelength and energy to inaudible frequencies. Determining the suitable frequency and wavelength takes place with choosing the value with adjustable equipment complying best with the temperature and angular offset.
  • a./ It ensures oxygen supply of the organism during a severe operation, while genuine blood can be preserved for intake after the operation.
  • the ambulance man providing first aid can ensure oxygen supply of the organism drained of blood irrespective of blood group until the injured can get fully efficient medical treatment.
  • the advantage of the process according to the invention is, that it is proper for producing artificial blood suitable for supplying blood temporarily for an organism of any blood group drained of blood.
  • the process is suitable for producing liposomes suitable to be used as artificial blood made from haemoglobin and from lipoids in organisms of vertebrata.
  • the particles of smaller size than genuine blood-cells (200- 500nm) are suitable for substituting the function of gas supply of red blood-cells. Production of artificial blood particles can take place with using haemoglobin of congener or foreign type.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Organic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The subject of the invention relates to a process for producing artificial blood, using haemoglobin lyophilized or obtained from fresh blood, suitable for supplying blood temporarily for an organism of any blood group drained of blood. The invention relates to a process producing artificial blood suitable for supplying blood temporarily for an organism of any blood group drained of blood. The process is suitable for producing liposomes suitable to be used as artificial blood made from haemoglobin and from lipoids in organisms of vertebrata. The particles of smaller size than genuine blood-cells (200-500nm) are suitable for substituting the function of gas supply of red blood-cells. Production of artificial blood particles can take place with using haemoglobin of congener or foreign type.

Description

ARTIFICIAL BLOOD MADE OF HEMOGLOBIN ENCAPSULATED IN LIPOSOMES
The subject of the invention relates to a process for producing artificial blood, using haemoglobin lyophilized or obtained from fresh blood, suitable for supplying blood temporarily for an organism of any blood group drained of blood.
During loss of blood three essential basic materials leave the organism:
1. Water, the fluid component of blood together with electrolytes dissolved in water.
2. Proteins together with enzymes and antibodies.
3. Cell elements, among them red blood cells accounting for supplying gases.
In the state of the art demand for supplying blood had long arisen. First results were achieved by restoring level of fluid content of blood in cases when considerable proportion of fluid content of blood was lost due to any physiological or pathological effect. In such dehydrated cases intake of fluid ensured restoring the patient from severe cases and created favourable conditions for healing. In cases of young children or elderly people it is very important to take this aspect into consideration, because loss of fluid could be fatal for endangered organisms. Most cases giving water can no longer help. In such cases patients should be supplied with water with infusion injected directly to circulation. Prevention of drying out could be life saving in case of both young children and adults belonging to any age group suffering from infection caused by Salmonella sp., Vibrio cholera, certain viruses etc.
Possibility of blood transfusion has been made use of in almost every medical treatment beside battlefields since Landsteiner elaborated blood groups.
Today, when pharmaceutical industry producing and doctors using blood preparations must pay particular attention to the prevention of today still incurable virus-infections, applying of blood preparations or blood-supplementing materials offering provisional solutions are of particular significance. Artificial blood offers a possibility for solving the problem of one of the most significant functions of blood, i.e. the supply of carbon dioxide and oxygen gases and supply of fluid arising due to loss of blood. Artificial blood helps the patient suffered considerable loss of blood through life danger arising due to loss of blood. The preparation due to its nature and conditions of production contains beyond doubt no infectious organisms mentioned above. With avoiding possibility of infection the patient is definitely not exposed to an additional effect endangering life.
Artificial blood is capable of substituting one of the functions of blood linked with the red blood cells, the transport of gases. It may help patient through biological ashpyxia arising due to shortage of blood. At the same time it makes up fluid deficiency in the organism, ensuring recovery of osmotic value of cells, and also provides possibility for the haematogens to restore the original composition of blood under physiological blood pressure and circulation conditions with as little delay as possible. If loss of blood is of such an extent, that urgent supply of other blood components (proteins, enzymes etc.) besides electrolytes is also required, then after supplying the artificial blood the possibility of the intake of genuine blood under hospital conditions of the patient can be ensured as well.
When working out the invention we set the aim to find a solution for producing artificial blood, using haemoglobin lyophilized or obtained from fresh blood.
When realizing the solution according to the invention we recognized, that said artificial blood contains haemoglobin locked into a lipoid shell in form of particles that can be suspended in a watery substance, and said particles are suitable or can be made suitable for supplying blood for all vertebrata, the set aim can be achieved.
The invention relates to a process for producing artificial blood, using haemoglobin lyophilized or obtained from fresh blood, characterized by that said artificial blood contains haemoglobin locked into a lipoid shell in form of particles that can be suspended in a watery substance, and said particles are suitable or can be made suitable for supplying blood for all vertebrata.
In a preferred application of the process according to the invention the size of the particles should remain below the size of the red-blood cells or red-blood corpuscles characteristic of the given species and said particles permeate through the tubes of the capillaries owing to their size.
In another preferred application of the process according to the invention the haemoglobin used derives directly from haemoglobin solution produced from blood or it is haemoglobin dried by lyophilization. From the point of view of application of artificial blood the haemoglobin advantageously is of congener type or derives from other vertebrata.
In a further preferred application of the process according to the invention during forming of the particles the material of the lipoid membrane covering the haemoglobin is built by one or more lipoid component.
In a further preferred application of the process according to the invention forming of the lipoid membrane takes place from starting from the lipoid or from the lipoid solvents and at a temperature higher than the melting point of the lipoids starting from the liquid lipoids.
The producing of the lipoid membrane takes place advantageously on solid, fluid surface or in gaseous substance. During the formation of the particles splitting of the membrane into particle size advantageously takes place under the influence of physical energy.
A preferable application of the artificial blood produced during the process according to the invention is, that the haemoglobin will not be washed away from the particles even after longer storage of under proper conditions. The artificial blood produced during the process according to the invention is stored either in liquid form or in lyophilized form, the powder suspended in the proper solution provides artificial blood of full value.
The process according to the invention is set forth by the following:
Physical principle of production:
Haemoglobin must be enveloped into a semi-permeable lipoid membrane to retain its capability for supplying oxygen and carbon dioxide. During the process the haemoglobin is put between two monomolecular lipoid membranes of properly arranged structure and liposomes are formed by splitting planparallel membranes. The other possibility is to put the haemoglobin on a monomolecular membrane and the membrane is splitted in a way, that the pieces of the membrane roll up the haemoglobin on their surface, similarly as cigarette paper covers tobacco. By packaging into the membrane it can be achieved, that the haemoglobin should not be dissolved during circulation, because dissolved haemoglobin is secreted in the kidneys.
Immunological conditions of preparation of artificial blood:
Overriding principle for the use of artificial blood is, that haemoglobin is closed into a liposome in such a way, that artificial blood should not have allergic influence. This requirement can be fulfilled so, that lipoids existing in the organism are used for forming the membrane substituting the cell membrane of the 'cells'of the artificial blood. Primarily those materials are used, which show the least variability during evolution. This solution has double benefits. The artificial blood produced is suitable not only for substitution and temporary supply of the blood of one race, namely the human, but the same blood can be used for the substitution, temporary supply of blood of almost any warm-blooded animal. The advantage of the theoretical and practical solution is, that the beneficial effect observed on one species of animals can be transferred even without modification to the other species. Obviously the human species, the Homo sapiens have the greatest benefit of all this, because every figure of the experimental results can be taken as of the same value of observations on humans beings.
Difficulties entitled with the task:
The complex containing haemoglobin may assume allergen characteristics in case the artificial 'cell membrane' acting as allergen or antigen is capable of stimulating anti-bodies damaging the organism in some way. This possibility must be taken into consideration even if lipoid molecules used by us do not usually appear as antigens or allergens. Nowadays it is not infrequent that material earlier not considered allergen by allergologists in fact act as allergens.
Autoantigenic behaviour of certain lipoids can not be excluded. Therefore we highlighted those lipoid combinations or basic materials which could sensibilize the organism with the least probability.
Possibility of overcoming side-effects
Our observations so far support our earlier working hypothesis, that a liposome can be produced with applying material with the least immunological power which can match the features of those of the natural cells or corpuscles produced in the organism.
The basic material of the membrane liposome of the artificial blood produced by us is compiled exclusively of lipoids that can be found during evolution in each family of the warm-blooded animals. It has no extraneous element, and no allergic effect in animal tests could be noticed. On basis of our achievements it seems realistic to achieve the set aim, i.e.our preparation will prove to be suitable for filling the function of blood as supplier of oxygen and carbon dioxide in all organisms drained of blood irrespective of blood group. As mentioned in the introduction, it is first of all suitable for meeting the demands of casualties and operations lasting for a relatively short time, but in a certain limited circle it ensures solution of medical treatment as well. On basis of the results of the animal tests carried out so far we find it suitable for use for human beings as well keeping in mind the theoretical considerations.
The process according to the invention will be shown with the following example:
Example 1
A melt or solution of the lipoid is produced at a proper temperature, which is suitable for making a thin monomolecular layer on a smooth surface.
The surface of the body, the temperature, the flowing speed of the solution or that of the lipoid melt should be optimum. The smooth surface can include dents of maximum 400 nm. The temperature can differ from the melting temperature by maximum 10% in case of certain lipoids. (obviously to the higher range). The flowing speed of lipoid can be 1 mg/sec/50 cm2 +-10% on a surface of a proper angle. The physical impacts consistent with the viscosity of the lipoid can range between electromagnetic waves (270 nm) of advantageously applicable frequency and energy through sound-waves of proper wavelength and energy to inaudible frequencies. Determining the suitable frequency and wavelength takes place with choosing the value with adjustable equipment complying best with the temperature and angular offset. We bring haemoglobin molecules in connection with lipoid producing lipoid shell under ideal conditions. The physical force arising at the moment of encounter splits the lipoid layer in the given size and it closes the haemoglobin. Liposomes produced this way are put into a liquid of around pH 7 value and are separated from haemoglobin molecules soluble or remaining outside the lipoid shell. The haemoglobin-solution is regained and the liposomes containing haemoglobin are collected for artificial blood.
Possible fields of application of the artificial blood according to the invention:
a./ It ensures oxygen supply of the organism during a severe operation, while genuine blood can be preserved for intake after the operation. b./ In case of an accident the ambulance man providing first aid can ensure oxygen supply of the organism drained of blood irrespective of blood group until the injured can get fully efficient medical treatment.
c.l Under warring conditions it is suitable for supplying the injured soldier drained of blood with blood until he is taken to hospital. Life of the soldier can be saved with applying artificial blood. Canned artificial blood in lyophilized form may be the part of personal equipment. Doctors on the battlefield should only take along physiological solvent, mix it with the powdered blood and it can be immediately injectioned.
ά.l In case of special therapy it is suitable for replacing blood during a relatively short physical therapy.
Q.I In case of another special therapy said particles of artificial blood have much smaller size, than the size of ordinary red blood cells, consequently said particles have much bigger surface. More efficient and faster exchange of gases can be ensured providing benefits in therapy.
The advantage of the process according to the invention is, that it is proper for producing artificial blood suitable for supplying blood temporarily for an organism of any blood group drained of blood. The process is suitable for producing liposomes suitable to be used as artificial blood made from haemoglobin and from lipoids in organisms of vertebrata. The particles of smaller size than genuine blood-cells (200- 500nm) are suitable for substituting the function of gas supply of red blood-cells. Production of artificial blood particles can take place with using haemoglobin of congener or foreign type.
Solution of the problem of artificial blood meets the requirements of an old demand, which appeared irrealistic many a time. Artificial blood might become one of the most significant achievements in overcoming problems arising due to loss of blood since blood transfusion was first carried out armed with the knowledge of blood groups elaborated by Landsteiner. Possibility of using haemoglobin of different races becomes realistic with the use of artificial blood. It requires additional research to state how the possibility of using giant molecules important in the supply of gases slipped into a liposome shell of immunologically neutral, or of weak antigenic feature can be made use of.
With the solution elaborated by us, we can provide users with 'blood corpuscles', which can be applied for supplying blood with using haemoglobin within the race. Experiences obtained through applying haemoglobin within the race will provide possibilities for research into the use of haemoglobin of foreign races. Unlimited quantities of artificial blood can be produced for the needy with the use of haemoglobin of foreign race. It can be realized in such a way, that presence and transmission of microorganisms endangering human organism can be with great certainty excluded.

Claims

CLAIMS:
1. Process for producing artificial blood, using haemoglobin lyophilized or obtained from fresh blood, characterized by that said artificial blood contains haemoglobin locked into a lipoid shell in form of particles that can be suspended in a watery substance, and said particles are suitable or can be made suitable for supplying blood for all vertebrata.
2. Process according to claim 1 characterized by that size of the particles should remain below the size of the red-blood cells or red-blood corpuscles characteristic of the given species and said particles permeate through the tubes of the capillaries owing to their size.
3. Process according to claims 1 to 2 characterized by that the haemoglobin used derives directly from haemoglobin solution produced from blood or it is haemoglobin dried by lyophilization.
4. Process according to claims 1 to 3 characterized by that from the point of view of application of artificial blood the haemoglobin is of congener type or derives from other vertebrata.
5. Process according to claims 1 to 4 characterized by that during forming of the particles the material of the lipoid membrane covering the haemoglobin is built by one or more lipoid component.
6. Process according to claim 5 characterized by that forming of the lipoid membrane takes place from starting from the lipoid or from the lipoid solvents and at a temperature higher than the melting point of the lipoids starting from the liquid lipoids.
7. Process according to claim 6 characterized by that producing of the lipoid membrane takes place on solid, fluid surface or in gaseous substance.
8. Process according to claims 1 to 7 characterized by that during the formation of the particles splitting of the membrane into particle size takes place under the influence of physical energy.
9. Process according to claims 1 to 8 characterized by that haemoglobin will not be washed away from the particles even after longer storage of under proper conditions.
10. Process according to claims 1 to 9 characterized by that artificial blood is stored either in liquid form or in lyophilized form, the powder suspended in the proper solution provides artificial blood of full value.
PCT/HU2002/000030 2001-04-27 2002-04-10 Artificial blood made of hemoglobin encapsulated in liposomes WO2002087540A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU0101713A HUP0101713A2 (en) 2001-04-27 2001-04-27 Process for the preparation of artificial blood
HUP0101713 2001-04-27

Publications (1)

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WO2002087540A1 true WO2002087540A1 (en) 2002-11-07

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004047807A1 (en) * 2002-11-26 2004-06-10 Horvath Istvan Artificial blood on the basis of encapsulted haemoglobin
US11604026B2 (en) 2019-03-14 2023-03-14 Terumo Bct Biotechnologies, Llc Lyophilization loading tray assembly and system
US11634257B2 (en) 2017-10-09 2023-04-25 Terumo Bct Biotechnologies, Llc Lyophilization container and method of using same

Citations (6)

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Publication number Priority date Publication date Assignee Title
US4133874A (en) * 1976-06-10 1979-01-09 The University Of Illinois Foundation Lipid encapsulated hemoglobin cells
WO1983000089A1 (en) * 1981-07-06 1983-01-20 Rush Presbyterian St Luke Preparation of synthetic erythrocytes
US4532130A (en) * 1981-07-06 1985-07-30 Rush-Presbyterian-St. Luke's Medical Center Preparation of synthetic frythrocytes
JPS6475418A (en) * 1987-09-14 1989-03-22 Terumo Corp Production of liposome
US4911929A (en) * 1986-08-29 1990-03-27 The United States Of America As Represented By The Secretary Of The Navy Blood substitute comprising liposome-encapsulated hemoglobin
JP2000051322A (en) * 1998-08-12 2000-02-22 Terumo Corp Processing method for hemoglobin solution, artificial blood and manufacture of artificial blood

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Publication number Priority date Publication date Assignee Title
US4133874A (en) * 1976-06-10 1979-01-09 The University Of Illinois Foundation Lipid encapsulated hemoglobin cells
WO1983000089A1 (en) * 1981-07-06 1983-01-20 Rush Presbyterian St Luke Preparation of synthetic erythrocytes
US4532130A (en) * 1981-07-06 1985-07-30 Rush-Presbyterian-St. Luke's Medical Center Preparation of synthetic frythrocytes
US4911929A (en) * 1986-08-29 1990-03-27 The United States Of America As Represented By The Secretary Of The Navy Blood substitute comprising liposome-encapsulated hemoglobin
JPS6475418A (en) * 1987-09-14 1989-03-22 Terumo Corp Production of liposome
JP2000051322A (en) * 1998-08-12 2000-02-22 Terumo Corp Processing method for hemoglobin solution, artificial blood and manufacture of artificial blood

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Title
DATABASE WPI Section Ch Week 200020, Derwent World Patents Index; Class B04, AN 2000-231493, XP002209821 *
GOINS B ET AL: "Liposome-encapsulated hemoglobin: historical development of a blood substitute.", BIOTECHNOLOGY (READING, MASS.) UNITED STATES 1991, vol. 19, 1991, pages 117 - 125, XP001097836, ISSN: 0740-7378 *
PATENT ABSTRACTS OF JAPAN vol. 013, no. 278 (C - 611) 26 June 1989 (1989-06-26) *
SPIRIG ANDREAS M ET AL: "Liposome encapsulated hemoglobin: A potential artificial blood substitute.", DRUGS OF THE FUTURE, vol. 18, no. 3, 1993, pages 249 - 253, XP001097845, ISSN: 0377-8282 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004047807A1 (en) * 2002-11-26 2004-06-10 Horvath Istvan Artificial blood on the basis of encapsulted haemoglobin
US11634257B2 (en) 2017-10-09 2023-04-25 Terumo Bct Biotechnologies, Llc Lyophilization container and method of using same
US11604026B2 (en) 2019-03-14 2023-03-14 Terumo Bct Biotechnologies, Llc Lyophilization loading tray assembly and system
US11609043B2 (en) 2019-03-14 2023-03-21 Terumo Bct Biotechnologies, Llc Lyophilization container fill fixture, system and method of use
US11609042B2 (en) 2019-03-14 2023-03-21 Terumo Bct Biotechnologies, Llc Multi-part lyophilization container and method of use
US11740019B2 (en) 2019-03-14 2023-08-29 Terumo Bct Biotechnologies, Llc Lyophilization loading tray assembly and system
US11747082B2 (en) 2019-03-14 2023-09-05 Terumo Bct Biotechnologies, Llc Multi-part lyophilization container and method of use
US11815311B2 (en) 2019-03-14 2023-11-14 Terumo Bct Biotechnologies, Llc Lyophilization container fill fixture, system and method of use
US11994343B2 (en) 2019-03-14 2024-05-28 Terumo Bct Biotechnologies, Llc Multi-part lyophilization container and method of use

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HU0101713D0 (en) 2001-07-30

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