CN106237314A - A kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid and preparation method thereof - Google Patents

A kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid and preparation method thereof Download PDF

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Publication number
CN106237314A
CN106237314A CN201610778626.4A CN201610778626A CN106237314A CN 106237314 A CN106237314 A CN 106237314A CN 201610778626 A CN201610778626 A CN 201610778626A CN 106237314 A CN106237314 A CN 106237314A
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China
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resuscitation fluid
preparation
aid
hemorrhagic shock
house pet
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黄宇彬
齐延新
谢志刚
景遐斌
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Changchun Institute of Applied Chemistry of CAS
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Changchun Institute of Applied Chemistry of CAS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/41Porphyrin- or corrin-ring-containing peptides
    • A61K38/42Haemoglobins; Myoglobins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0026Blood substitute; Oxygen transporting formulations; Plasma extender
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions

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

Abstract

The present invention provides a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid and preparation method thereof, belongs to resuscitation fluid preparation method field.Solve existing blood substitute component single, the most single oxygen supply, problem less for expanding blood volume effect.Bovine hemoglobin solution and glutaraldehyde solution are first reacted by the method, centrifugal, obtain the hemoglobin particle after glutaraldehyde cross-linking;Then the hemoglobin particle after the glutaraldehyde cross-linking that will obtain mixes with injection, obtains being applied to the resuscitation fluid of house pet hemorrhagic shock first aid;Described injection is HES, HES2000 or normal saline.The present invention also provides for the resuscitation fluid that above-mentioned preparation method obtains.The preparation method of the present invention is simple, raw material is easy to get, and the resuscitation fluid prepared can the most reversibly combine and discharge oxygen and expanding blood volume simultaneously.

Description

A kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid and preparation method thereof
Technical field
The invention belongs to resuscitation fluid preparation method field, be specifically related to a kind of recovery being applied to house pet hemorrhagic shock first aid Liquid and preparation method thereof.
Background technology
Blood transfusion is that the one supplementing animal blood or a certain composition safely and effectively saves life therapy.The blood of adult dogs Having 80~90ml/kg, the blood of cat has 80~90ml/kg, when generation acute bleeding of wounding or perform the operation reaches botal blood volume 1/5, and can Occur that blood pressure reduces, palpitating speed.When reaching 1/3 when losing blood, by crisis life, now blood transfusion in time is the most effective of redemption life Method.Blood transfusion can not only replenishment of blood content, and the erythrocyte increased can increase oxygen carrying content, improves the function of cardiac muscle and brain.Mesh Before compare in the world it is recognized that similar with the mankind, the blood group of cat has A type, Type B and three kinds of blood groups of AB type.Canis familiaris L. not only has blood group, And 7 kinds can be divided into, it is CEA-1 (A)-CEA-8 (G) totally 8 factors respectively.Wherein the antigenicity of the A factor is the strongest, be face examine defeated The factor mainly considered during blood, otherwise can cause, by a large amount of haemolysis of erythrocyte in blood Canis familiaris L. body, suffering a shock rapidly.Clinically to house pet Blood transfusion not only needs cross match blood test, and veterinary personnel must grasp indication and contraindication, carries out for blood supply house pet Strict screening and blood sampling, have strict demand simultaneously for transfusion volume and speed, if Canis familiaris L. once maximum transfusion volume is its botal blood volume 10%~20%.Transfusion speed, during acute massive hemorrhage, can be by 100 milliliters of blood speed of input in 5~6 minutes, in addition, It is advisable with slow input.Also exist that heating, allergy, haemolysis, circulating load be overweight simultaneously, hypocalcemia and blood clotting sick etc. bad Reaction.
External it is usually by animal welfare protection mechanism Lai Jian blood bank, the developed country such as the U.S., Australia animal Blood bank, is to set up with the form of blood bank of central authorities.In China, similar blood bank not yet occurs, pet clinic set up blood bank the most less Reality, distribution type and detection are required for import equipment, and cost is the highest.The preservation of blood is also a great problem, sets up large-scale dynamic simultaneously Thing blood bank then needs the blood source found reliably and with long-term, further relate to raise blood supply animal, quarantine, multiple links such as die a natural death, so temporarily Shi Wufa realizes.
Therefore a kind of emergency resuscitation liquid confession house pet utilization being capable of supply that and retaining for a long time, use at any time is prepared, it is not necessary to look into See whether blood group mates, the most do not infect the danger of virus, and with low cost, the difficulty of house pet blood transfusion first aid can be solved Topic.
Blood generation based on glutaraldehyde polymeric hemoglobin in the applying for a patent of wheat moral one hundred Ou Famu company limited of Russia Articles for use (CN102026654A), but component is single, the most single oxygen supply, less for expanding blood volume effect.
Summary of the invention
The invention aims to solve existing blood substitute component single, the most single oxygen supply, for expanding blood The less problem of capacity effect, and a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid and preparation method thereof is provided.
Present invention firstly provides the preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid, the method bag Include:
Step one: bovine hemoglobin solution and glutaraldehyde solution are reacted, centrifugal, obtain the blood red egg after glutaraldehyde cross-linking White particle;
Step 2: the hemoglobin particle after glutaraldehyde cross-linking step one obtained mixes with injection, is applied Resuscitation fluid in house pet hemorrhagic shock first aid;
Described injection is HES, HES2000 or normal saline.
Preferably, the concentration of described bovine hemoglobin solution is 1-40mg/ml.
Preferably, the concentration of described glutaraldehyde solution is 0.025-0.25%.
Preferably, described bovine hemoglobin solution and the mol ratio of glutaraldehyde solution are (1-10): 1.
Preferably, described step one reaction temperature is room temperature, and the response time is 8-14h.
Preferably, described centrifugal speed is 2000rpm, and centrifugation time is 5-15min.
Preferably, the hemoglobin particle after described glutaraldehyde cross-linking is 1:1-1:10 with the mass ratio of injection.
The present invention also provides for the resuscitation fluid being applied to house pet hemorrhagic shock first aid that above-mentioned preparation method obtains.
Beneficial effects of the present invention
Present invention firstly provides the preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid, the method first will Bovine hemoglobin solution and glutaraldehyde solution reaction, centrifugal, obtain the hemoglobin particle after glutaraldehyde cross-linking;Then will obtain Glutaraldehyde cross-linking after hemoglobin particle mix with injection, obtain being applied to the resuscitation fluid of house pet hemorrhagic shock first aid; Described injection is HES, HES2000 or normal saline.The preparation method of the present invention is simple, raw material is easy to get, and prepares Resuscitation fluid can the most reversibly combine and discharge oxygen and simultaneously expanding blood volume.
The present invention also provides for the resuscitation fluid that above-mentioned preparation method obtains, and described resuscitation fluid gas transfer capability is good, energy It is enough oxygen-starved tissue and organ oxygen supply, the resuscitation fluid non-cellular analyte product of the present invention, acellular surface antigen, it is not necessary to blood is joined Type, the strict source controlling bovine hemoglobin, it is possible to avoid infectious disease to propagate, without immunoreation, can preserve for a long time.
Accompanying drawing explanation
Fig. 1 is that the gas transformation energy of the embodiment of the present invention 1 resuscitation fluid is tried hard to;
Fig. 2 is that the embodiment of the present invention 1 resuscitation fluid and plasma substitute are to hemorrhagic shock rats model resuscitation effect figure;
Fig. 3 is that the embodiment of the present invention 1 resuscitation fluid and plasma substitute are to hemorrhagic shock rats model recovery survival curve figure.
Detailed description of the invention
Present invention firstly provides the preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid, the method bag Include:
Step one: bovine hemoglobin solution and glutaraldehyde solution are reacted, centrifugal, obtain the blood red egg after glutaraldehyde cross-linking White particle;
Step 2: the hemoglobin particle after glutaraldehyde cross-linking step one obtained mixes with injection, is applied Resuscitation fluid in house pet hemorrhagic shock first aid;
Described injection is HES, HES2000 or normal saline.
According to the present invention, prepare bovine hemoglobin solution and glutaraldehyde solution, described bovine hemoglobin solution the most respectively Concentration be preferably 1-40mg/ml;The concentration of described glutaraldehyde solution is preferably 0.025-0.25%.
According to the present invention, the above-mentioned bovine hemoglobin solution prepared and glutaraldehyde solution are mixed, reacts, will be anti- Answer thing to be centrifuged, obtain the hemoglobin particle after glutaraldehyde cross-linking;
Described reaction temperature is preferably room temperature, and the response time is preferably 8-14h, more preferably 12h,
Described bovine hemoglobin solution and the mol ratio of glutaraldehyde solution are preferably (1-10): 1;More preferably 4:1;Institute The centrifugal speed stated is preferably 2000rpm, and centrifugation time is preferably 5-15min.
According to the present invention, the hemoglobin particle after glutaraldehyde cross-linking is mixed with injection, the solution after preparation is existed Carry out deoxidation state conversion under carbon monoxide protection, after conversion, carry out filtration sterilization sterilization, preserve under normal temperature and vacuum conditions, answered Resuscitation fluid for house pet hemorrhagic shock first aid;
Described injection is HES (Hydroxyethyl starch sodium chloride injection), HES2000 (hetastarch sodium chloride 2000 injection) or normal saline.Hemoglobin particle after described glutaraldehyde cross-linking is preferably with the mass ratio of injection 1:(1-10), more preferably 1:4.
The present invention also provides for the resuscitation fluid being applied to house pet hemorrhagic shock first aid that above-mentioned preparation method obtains.Described answers Soviet Union's liquid gas transfer capability is good, it is possible to for oxygen-starved tissue and organ oxygen supply, the resuscitation fluid non-cellular analyte product of the present invention, without thin Cellular surface antigen, it is not necessary to Blood zygosity, the strict source controlling bovine hemoglobin, it is possible to avoid infectious disease to propagate, without exempting from Epidemic disease is reacted, and can preserve for a long time.
Below in conjunction with specific embodiment, the present invention is done further detailed description, embodiment relates to raw material and all uses Commercially available.
Embodiment 1
By bovine hemoglobin solution (concentration is 30mg/ml) and glutaraldehyde solution (concentration is 0.01%) according to mol ratio 4: 1 mixing, at room temperature carries out reacting 12h, carries out being centrifuged 10min at 2000rpm by reactant, obtain the blood after glutaraldehyde cross-linking Lactoferrin particle;
Hemoglobin particle after glutaraldehyde cross-linking is mixed according to mass ratio 1:4 with HES, by the solution after preparation one Carry out deoxidation state conversion under carbonoxide protection, after conversion, carry out filtration sterilization sterilization, preserve under normal temperature and vacuum conditions, be applied Resuscitation fluid in house pet hemorrhagic shock first aid.
Fig. 1 is that the gas transformation energy of the embodiment of the present invention 1 resuscitation fluid is tried hard to, it will be seen from figure 1 that this resuscitation fluid can be taken Band oxygen and releasing oxygen, possess combination and the releasability of oxygen.
Resuscitation fluid and plasma substitute input that Shock in Rats carries out embodiment 1 preparation contrast, and Fig. 2 is that the present invention implements Example 1 resuscitation fluid and plasma substitute are to hemorrhagic shock rats model resuscitation effect figure;Fig. 3 is the embodiment of the present invention 1 resuscitation fluid and generation Blood plasma is to hemorrhagic shock rats model recovery survival curve figure, from figures 2 and 3, it will be seen that the resuscitation fluid of the input present invention Rear mean arterial pressure (MP) is down to extreme value in blood-letting, recovers with liquid infusion blood volume, and blood pressure has raised, the survival of rats of 70% More than 2h, illustrate that the resuscitation fluid of the present invention can effectively recovery Shock in Rats.After input plasma substitute, MAP is down to extreme value in blood-letting, Blood pressure does not raises, and the survival of rats time, not less than 1 hour, illustrates that plasma substitute fails effective recovery Shock in Rats.
Embodiment 2
By bovine hemoglobin solution (concentration is 30mg/ml) and glutaraldehyde solution (concentration is 0.01%) according to mol ratio 4: 1 mixing, at room temperature carries out reacting 12h, carries out being centrifuged 10min at 2000rpm by reactant, obtain the blood after glutaraldehyde cross-linking Lactoferrin particle;
Hemoglobin particle after glutaraldehyde cross-linking is mixed according to mass ratio 1:4 with HES2000, by the solution after preparation Under carbon monoxide is protected, carry out deoxidation state conversion, after conversion, carry out filtration sterilization sterilization, preserve under normal temperature and vacuum conditions, obtain It is applied to the resuscitation fluid of house pet hemorrhagic shock first aid.
Shock in Rats is carried out the resuscitation fluid of embodiment 2 preparation, after the resuscitation fluid of the input present invention, mean arterial pressure (MP) Being down to extreme value in blood-letting, recover with liquid infusion blood volume, blood pressure has raised, and the survival of rats of 65%, more than 2h, illustrates this Bright resuscitation fluid can effectively recovery Shock in Rats.
Embodiment 3
By bovine hemoglobin solution (concentration is 30mg/ml) and glutaraldehyde solution (concentration is 0.01%) according to mol ratio 4: 1 mixing, at room temperature carries out reacting 12h, carries out being centrifuged 10min at 2000rpm by reactant, obtain the blood after glutaraldehyde cross-linking Lactoferrin particle;
Hemoglobin particle after glutaraldehyde cross-linking is mixed according to mass ratio 1:4 with normal saline, will preparation after molten Liquid carries out deoxidation state conversion under carbon monoxide is protected, and carries out filtration sterilization sterilization after conversion, preserves under normal temperature and vacuum conditions, To the resuscitation fluid being applied to house pet hemorrhagic shock first aid.
Shock in Rats is carried out the resuscitation fluid of embodiment 3 preparation, after the resuscitation fluid of the input present invention, mean arterial pressure (MP) Being down to extreme value in blood-letting, recover with liquid infusion blood volume, blood pressure has raised, and the survival of rats of 50%, more than 1h, illustrates this Bright resuscitation fluid can effectively recovery Shock in Rats.
Embodiment 4
By bovine hemoglobin solution (concentration is 30mg/ml) and glutaraldehyde solution (concentration is 0.01%) according to mol ratio 1: 1 mixing, at room temperature carries out reacting 8h, carries out being centrifuged 5min at 2000rpm by reactant, and obtain after glutaraldehyde cross-linking is blood red Albumen particle;
Hemoglobin particle after glutaraldehyde cross-linking is mixed according to mass ratio 1:1 with HES, by the solution after preparation one Carry out deoxidation state conversion under carbonoxide protection, after conversion, carry out filtration sterilization sterilization, preserve under normal temperature and vacuum conditions, be applied Resuscitation fluid in house pet hemorrhagic shock first aid.
Shock in Rats is carried out the resuscitation fluid of embodiment 4 preparation, after the resuscitation fluid of the input present invention, mean arterial pressure (MP) Being down to extreme value in blood-letting, recover with liquid infusion blood volume, blood pressure has raised, and the survival of rats of 60%, more than 1h, illustrates this Bright resuscitation fluid can effectively recovery Shock in Rats.
Embodiment 5
By bovine hemoglobin solution (concentration is 30mg/ml) and glutaraldehyde solution (concentration is 0.01%) according to mol ratio 10:1 mixes, and at room temperature carries out reacting 14h, carries out being centrifuged 15min at 2000rpm, after obtaining glutaraldehyde cross-linking by reactant Hemoglobin particle;
Hemoglobin particle after glutaraldehyde cross-linking is mixed according to mass ratio 1:10 with HES, the solution after preparation is existed Carry out deoxidation state conversion under carbon monoxide protection, after conversion, carry out filtration sterilization sterilization, preserve under normal temperature and vacuum conditions, answered Resuscitation fluid for house pet hemorrhagic shock first aid.
Shock in Rats is carried out the resuscitation fluid of embodiment 5 preparation, after the resuscitation fluid of the input present invention, mean arterial pressure (MP) Being down to extreme value in blood-letting, recover with liquid infusion blood volume, blood pressure has raised, and the survival of rats of 65%, more than 1h, illustrates this Bright resuscitation fluid can effectively recovery Shock in Rats.

Claims (8)

1. the preparation method of the resuscitation fluid being applied to house pet hemorrhagic shock first aid, it is characterised in that the method includes:
Step one: bovine hemoglobin solution and glutaraldehyde solution are reacted, centrifugal, obtain the hemoglobin grain after glutaraldehyde cross-linking Son;
Step 2: the hemoglobin particle after glutaraldehyde cross-linking step one obtained mixes with injection, obtains being applied to dote on The resuscitation fluid of thing hemorrhagic shock first aid;
Described injection is HES, HES2000 or normal saline.
The preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid the most according to claim 1, its feature Being, the concentration of described bovine hemoglobin solution is 1-40mg/ml.
The preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid the most according to claim 1, its feature Being, the concentration of described glutaraldehyde solution is 0.025-0.25%.
The preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid the most according to claim 1, its feature Being, described bovine hemoglobin solution and the mol ratio of glutaraldehyde solution are (1-10): 1.
The preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid the most according to claim 1, its feature Being, described step one reaction temperature is room temperature, and the response time is 8-14h.
The preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid the most according to claim 1, its feature Being, described centrifugal speed is 2000rpm, and centrifugation time is 5-15min.
The preparation method of a kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid the most according to claim 1, its feature Being, the hemoglobin particle after described glutaraldehyde cross-linking is 1:1-1:10 with the mass ratio of injection.
8. the resuscitation fluid being applied to house pet hemorrhagic shock first aid that the preparation method described in claim 1-7 any one obtains.
CN201610778626.4A 2016-08-30 2016-08-30 A kind of resuscitation fluid being applied to house pet hemorrhagic shock first aid and preparation method thereof Pending CN106237314A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4390521A (en) * 1980-04-11 1983-06-28 Exxon Research And Engineering Co. Artificial red cells
CN101917970A (en) * 2007-12-22 2010-12-15 卡斯伯特·O·辛普金斯 Resuscitation fluid
CN102026654A (en) * 2008-03-18 2011-04-20 麦德佰欧法姆有限公司俄罗斯联邦 Oxygen-transferring blood substitute and a pharmaceutical composition (variants)

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4390521A (en) * 1980-04-11 1983-06-28 Exxon Research And Engineering Co. Artificial red cells
CN101917970A (en) * 2007-12-22 2010-12-15 卡斯伯特·O·辛普金斯 Resuscitation fluid
CN102026654A (en) * 2008-03-18 2011-04-20 麦德佰欧法姆有限公司俄罗斯联邦 Oxygen-transferring blood substitute and a pharmaceutical composition (variants)

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