NL1035741C2 - Method for obtaining extracellular hemoglobin blood from ragworm species e.g. Nereis diversicolor, involves utilizing nontoxic extracellular hemoglobin of Nereis diversicolor and Nereis virens for human blood substitute - Google Patents
Method for obtaining extracellular hemoglobin blood from ragworm species e.g. Nereis diversicolor, involves utilizing nontoxic extracellular hemoglobin of Nereis diversicolor and Nereis virens for human blood substitute Download PDFInfo
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- NL1035741C2 NL1035741C2 NL1035741A NL1035741A NL1035741C2 NL 1035741 C2 NL1035741 C2 NL 1035741C2 NL 1035741 A NL1035741 A NL 1035741A NL 1035741 A NL1035741 A NL 1035741A NL 1035741 C2 NL1035741 C2 NL 1035741C2
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- nereis
- blood
- diversicolor
- extracellular hemoglobin
- hemoglobin
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- 108010054147 Hemoglobins Proteins 0.000 title claims abstract description 34
- 102000001554 Hemoglobins Human genes 0.000 title claims abstract description 34
- 239000003633 blood substitute Substances 0.000 title claims abstract description 25
- 241000680905 Alitta virens Species 0.000 title claims abstract description 14
- 241000588205 Hediste diversicolor Species 0.000 title claims abstract description 14
- 210000004369 blood Anatomy 0.000 title claims description 25
- 239000008280 blood Substances 0.000 title claims description 25
- 238000000034 method Methods 0.000 title abstract description 3
- 231100000252 nontoxic Toxicity 0.000 title abstract description 3
- 230000003000 nontoxic effect Effects 0.000 title abstract description 3
- 241000894007 species Species 0.000 title description 7
- 241001327162 Garrodia nereis Species 0.000 title 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 230000001717 pathogenic effect Effects 0.000 claims description 6
- 241000282412 Homo Species 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 231100000331 toxic Toxicity 0.000 claims description 3
- 230000002588 toxic effect Effects 0.000 claims description 3
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 5
- 244000052769 pathogen Species 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000012678 infectious agent Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000024777 Prion disease Diseases 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 231100000676 disease causative agent Toxicity 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- WTWWXOGTJWMJHI-UHFFFAOYSA-N perflubron Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br WTWWXOGTJWMJHI-UHFFFAOYSA-N 0.000 description 2
- 229960001217 perflubron Drugs 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 241000046326 Alitta Species 0.000 description 1
- 241000243818 Annelida Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 101710141969 Extracellular globin Proteins 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
- 241000243827 Nereis Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 241000710886 West Nile virus Species 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000008384 membrane barrier Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
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
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The method involves utilizing a nontoxic extracellular hemoglobin of Nereis diversicolor and Nereis virens for human blood substitute.
Description
Extracellular hemoglobin blood substitute derived from ragworm species and the use thereof.
The current invention relates to an extracellular hemoglobin blood substitute, in particular an extracellular 5 hemoglobin derived from Nereis virens and/or Nereis diversicolor and the use thereof, in particular the use thereof in humans.
During medical practices, such as surgery or a treatment of a patient suffering from trauma, or in case of 10 blood-related diseases such as haemophilia, general and/or sickle-cell anaemia it may be necessary to supply a patient with blood by means of a blood transfusion. During such a blood transfusion, blood from a blood donor is injected intravenously in the circulatory system of a patient.
15 Several medical problems can arise as a result of a blood transfusion with contaminated or incompatible blood. Recipients can contract infectious agents, such as HIV, HTLV, hepatitis (A,B,C) viruses, Treponema, pallidum; the causative agent of syphilis, West Nile Virus, Plasmodium,· 20 the causative agent of malaria, cytomegalovirus or transmittable spongiform encephalopathy such as Creutzfeldt-Jacob disease caused by prions. Furthermore, when recipients are administered incompatible blood, an agglutination reaction may take place which could have serious medical 25 consequences.
During modern medical practices, blood from each donor is tested to prevent the occurrence of medical complications and infections to ensure the patients health as well as possible. Therefore, donor blood is tested for 30 its compatibility group and for the presence of most of the pathogens or disease causing agents described above.
However, several drawbacks are known from such tests. First, these tests are expensive. Second, tests may not provide 1035741 2 complete information about the presence of contaminants.
E.g. most tests are based on the presence of antibodies which are made by the human immunological system and directed against antigens of pathogens. When a test is 5 carried out on contaminated blood in which no antibodies are present yet, a test for such a pathogen may or will result in a false-negative result, meaning the test indicates that no infectious agents are present while in fact such an agent is present. In such cases, the consequence could be that 10 contaminated blood is transfused into the recipient, infecting this person with the respective pathogen. Third, care should be taken that test results are not switched between blood bags.
Nowadays another issue involving the supply of 15 blood by blood donations is becoming clear. The number of blood donors is diminishing which consequently leads to problems with blood supply. This problem is due to increased concern among donors to contract an infectious disease.
Several methods have been developed to some extent 20 with the aim to circumvent the problems as described above. Research in this field includes the development of artificial blood substitutes as synthetic chemicals (Clark and Gollan, 1966) or via the synthesis of biological products (Chang, 1957; Chang, 1964).
25 Perfluorocarbons (PFCs) have been used as synthetic chemicals. PFCs are chemicals capable of transporting oxygen, and able to dissolve a large quantity of gas, such as oxygen and carbon dioxide. PFCs have the advantage that their oxygen-carrying capacity is in direct 30 correlation to the quantity of oxygen in the lungs. Also, PFCs can transport oxygen to tissues more rapidly as there are no membrane barriers to take. However, long-term retention of PFCs has not been studied in detail. Reports 3 are known of PFCs causing edemas as they accumulated in the tissues of the organism (Clark and Gollan, 1966; Sloviter and Kamimoto, 1967) . Also, problems connected to side effects, storage, high costs and the low efficiency of this 5 product are known (Mitsuno and Naito, 1979). Derivatives of PFC's, namely PFBO (perfluorooctylbromide) have been developed that have enhanced properties. But an increase in the quantity of oxygen in the blood has been reported to give rise to the formation of superoxide-type radical oxygen 10 (Reiss, 1991). Therefore, although progress in this field is substantial, considerable side-effects are still known and prevent such products from being used on a commercial scale.
Work has been carried out in the field of the synthesis of biological products as well. Blood substitutes 15 have been developed by modifying the structure of natural hemoglobin (Chang, 1957; Chang, 1997). To meet this end, modified-hemoglobin-type blood substitutes have been made from hemoglobins from genetically modified microorganisms, or of human or animal origin, such as the bovine hemoglobin 20 molecule. The immunology of the bovine hemoglobulin differs from human hemoglobin, but it transports oxygen to the tissues more easily. Nevertheless, the risks connected to xenotransfusions (interspecies transfusions) are considerable in light of (retro)viral infections or 25 spongiform-encephalopathy-type transmittals.
More recently, research has been conducted on stem cells (Giarratana et al, 2004), placental or umbilical cord blood as source of blood for transfusions.
However, these latter studies are not expected to 30 alleviate the limited supply of donor blood as a consequence of the low availability of umbilical cords and because of the high costs and ethical issues that are involved in stem cell research.
4
Some Annelids, such as Nereis virens and/or Nereis diversicolor are reported to have at least three types of globins (Weber and Vinogradov, 2001), of which the extracellular globin of Nereis virens and/or Nereis 5 diversicolor, which is dissolved in circulating body fluids, has excellent properties for it to be useful as blood substitute. It is therefore an object of the current invention to propose a solution to the above-addressed issues through the use, in particular in humans, of an 10 extracellular hemoglobin blood substitute from Nereis virens and/or Nereis diversicolor. The invention also concerns a blood substitute, in particular a human blood substitute, comprising an extracellular hemoglobin from the species Nereis virens and/or Nereis diversicolor.
15 In a preferred embodiment of the invention, the extracellular hemoglobin that can be used as blood substitute is from the ragworm species, Nereis virens. In another embodiment of the invention, the extracellular hemoglobin is from Nereis diversicolor.
20 Both species have several characteristics that allow them to be used as a source for extracellular hemoglobin. They can be cost-effectively reared and bred in huge numbers, there are no infectious agents known to be present in these ragworm species that could cause harmful 25 contaminations in humans and the extracellular hemoglobins can be isolated from the animals with relative ease and relative low investments (Rousselot et al, 2006). Further, the extracellular hemoglobin molecules are particularly suitable for use as a human blood substitute as there are no 30 incompatibility reactions known or expected to occur when using the extracellular hemoglobins, there are indications that the extracellular hemoglobins can function independently from any molecule or cofactors in releasing 5 oxygen. The extracellular hemoglobin is further characterized by the following properties: is can bind approximately 156 oxygen molecules, and it has a molecular size which is approximately 245 times lower than that of the 5 human hemoglobin molecules. The combination of these latter properties, especially the higher affinity to oxygen molecules, in other wording, higher capacity to bind such oxygen molecules, and the smaller molecular size of any of the ragworm extracellular hemoglobins, make such 10 extracellular hemoglobin particularly suitable as a blood substitute.
In a preferred embodiment, the extracellular hemoglobin possesses the following properties: it is nontoxic for the recipient, it is non-pathogenic, it is 15 transfusable into at least one, and preferably, all human blood types, it does not cause any undesired side effects in the recipient.
The term 'blood substitute' pertains to a product which has the capacity to replace the fvinetion exerted by 20 hemoglobin of red blood cells and which has the capacity to perform its functions in transporting blood gases. The term 'human blood substitute' refers to a blood substitute from Nereis virens and/or Nereis diversicolor that can be applied in humans as blood substitute as described above. The term 25 'extracellular hemoglobin' pertains to hemoglobin which is dissolved in bodily fluids, as opposed to being contained in red blood cells. The term 'toxic' pertains to biological or chemical compounds that could give rise to physiological changes or pathological disorders. The expression 'non-30 toxic' means that the blood substitute does not cause any pathological effects. The expression 'non-pathogenic' pertains to the absence of pathogenic agents. The expression 'transfusable into all blood types' refers to a universal 6 donor type hemoglobin which does not cause agglutination reactions. The expression 'does not cause any side effects' means that the extracellular hemoglobin does not cause any obvious.or non-obvious pathological effects in the 5 recipient. The term 'Ragworm' refers to both Nereis diversicolor (O.F. Müller, 1776), also known as Neanthus diversicolor (O.F. Müller, 1776) or Hediste diversicolor (O.F. Müller, 1776), and it refers to Nereis virens (M.
Sars, 1835) or Neanthus virens (M. Sars, 1835) or Alitta 10 virens (M. Sars, 1835) . The latter may also be known as King Ragworm. In Dutch, these species may be known as "Veelkleurige Zééduizendpoot" (N. diversicolor) en "Zager" (N. virens). However, the names of these species are sometimes interchangeably used, whereby "Zager" may also be 15 used to refer to N. diversicolor and whereby "Veelkleurige Zééduizendpoot" may be used to refer to N. virens.
References
Giarratana MC, Kobari L, Lapillonne H, Chalmers D, Kiger L, 20 Cynober T, Marden MC, Wajcman H, Douay L. Nat Biotechnol, 23:69-74 (2005).
Clark LCJ and Gollan F. Science, 152:1755 (1966).
Chang TMS. Hemoglobin Corposcules, McGill University (1957). Chang TMS. Science, 146:524-525 (1964).
25 Mitsuno T and Naito R. Excerpta Medica (1979).
Weber RE and Vinogradov SN. Physiol Rev, 81:569-628 (2001). Reiss JG. Vox sang, 61:225-239 (1991).
Sloviter H and Kamimoto T. Nature, 216:458 (1967).
30 1035741
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL1035741A NL1035741C2 (en) | 2008-07-23 | 2008-07-23 | Method for obtaining extracellular hemoglobin blood from ragworm species e.g. Nereis diversicolor, involves utilizing nontoxic extracellular hemoglobin of Nereis diversicolor and Nereis virens for human blood substitute |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL1035741A NL1035741C2 (en) | 2008-07-23 | 2008-07-23 | Method for obtaining extracellular hemoglobin blood from ragworm species e.g. Nereis diversicolor, involves utilizing nontoxic extracellular hemoglobin of Nereis diversicolor and Nereis virens for human blood substitute |
| NL1035741 | 2008-07-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL1035741C2 true NL1035741C2 (en) | 2010-01-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL1035741A NL1035741C2 (en) | 2008-07-23 | 2008-07-23 | Method for obtaining extracellular hemoglobin blood from ragworm species e.g. Nereis diversicolor, involves utilizing nontoxic extracellular hemoglobin of Nereis diversicolor and Nereis virens for human blood substitute |
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| Country | Link |
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| NL (1) | NL1035741C2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107495341A (en) * | 2017-08-17 | 2017-12-22 | 广东恩创生物科技有限公司 | A kind of edible clam worm and preparation method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030181358A1 (en) * | 2000-05-31 | 2003-09-25 | Franck Zal | Use a high-molecular-weight extracellular haemoglobin as a blood substitute |
-
2008
- 2008-07-23 NL NL1035741A patent/NL1035741C2/en not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030181358A1 (en) * | 2000-05-31 | 2003-09-25 | Franck Zal | Use a high-molecular-weight extracellular haemoglobin as a blood substitute |
Non-Patent Citations (2)
| Title |
|---|
| ECONOMIDES A P ET AL: "The respiratory function of the blood of neanthes(= nereis) virens (SARS) (polychaeta nereidae)", COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART A. COMPARATIVE PHYSIOLOGY, ELSEVIER SCIENCE LTD, US, vol. 51, no. 1, 1 May 1975 (1975-05-01), pages 219 - 223, XP023590958, ISSN: 0300-9629, [retrieved on 19750501] * |
| SUZUKI T ET AL: "The giant extracellular hemoglobin from the polychaete Neanthes diversicolor. The cDNA-derived amino acid sequence of linker chain L2 and the exonintron boundary conserved in linker genes", BIOCHIMICA ET BIOPHYSICA ACTA . GENE STRUCTURE AND EXPRESSION, ELSEVIER, AMSTERDAM, NL, vol. 1217, no. 3, 6 April 1994 (1994-04-06), pages 291 - 296, XP023137662, ISSN: 0167-4781, [retrieved on 19940406] * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107495341A (en) * | 2017-08-17 | 2017-12-22 | 广东恩创生物科技有限公司 | A kind of edible clam worm and preparation method |
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Effective date: 20190801 |