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Biodegradable nano-particles bonded with hemoglobin and production method thereof

A technology of hemoglobin and nanoparticles, which is applied in the field of biodegradable nanoparticles bonded with hemoglobin molecules and its preparation method, can solve the problems of lack of advantages, complicated process, and expensive phospholipids, and achieve the reduction of escape or leakage, mechanical The effect of high strength and less damage

Active Publication Date: 2008-11-19
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

From the current point of view, the price of capsule-type artificial red blood cells does not have an advantage, especially the price of phospholipids is expensive, the process is relatively complicated, and the form of physical packaging cannot avoid the phenomenon of sudden release of hemoglobin

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1: 1.0g PEG800 was placed in a polymerization reaction bottle, after azeotropic water removal with 30ml toluene, 2.5g 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2- Ketone (MPC) monomer, under the protection of nitrogen, add 1 / 200 moles of ethyl zinc as a catalyst, polymerize at 120 ° C for 12 hours, and then add 20.0 g of lactate to the reaction bottle under anhydrous and oxygen-free conditions The ester monomer was polymerized at 120°C for 12 hours. After the reaction, the reaction bottle was cooled to room temperature, the toluene was drained, the polymer was dissolved in chloroform, settled with cold methanol, washed, and vacuum-dried to obtain a triblock PML copolymer. Dissolve 0.1g of PML polymer in 10ml of tetrahydrofuran, add dropwise 40ml of secondary water at a rate of 0.05ml per minute, and remove the tetrahydrofuran with rotary evaporation after the dropwise addition to obtain an aqueous solution of PML micelles, which can be obtained by lyophilizatio...

Embodiment 2

[0031] Example 2: 1.0g of PEG10000 was placed in a polymerization reaction bottle, and after azeotropic water removal with 30ml of toluene, 4.0g of 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2- Ketone (MPC) monomer, under the protection of nitrogen, add 1 / 200 moles of ethyl zinc as a catalyst, polymerize at 120°C for 12 hours, and then add 1.0 g of lactate to the reaction bottle under anhydrous and oxygen-free conditions The ester monomer was polymerized at 120°C for 12 hours. After the reaction, the reaction bottle was cooled to room temperature, the toluene was drained, the polymer was dissolved in chloroform, settled with cold methanol, washed, and vacuum-dried to obtain a triblock PML copolymer. Dissolve 50mg porcine hemoglobin in 5ml PBS solution, add 6mmol NaN 3 , shake overnight at 20°C to obtain an azide hemoglobin solution, add 50mg of PML copolymer to the solution, and then add 6mmol of copper sulfate, sodium ascorbate and histidine respectively, continue to shake a...

Embodiment 3

[0033] Example 3: 6.5g of PEG5000 was placed in a polymerization reaction bottle, after azeotropic water removal with 30ml of toluene, 0.6g of 5-methyl-5-benzyloxycarbonyl-1,3-dioxane-2-one was added (MBC) monomer, under the protection of nitrogen, add 1 / 200 moles of ethyl zinc as a catalyst, polymerize at 120°C for 12 hours, and then add 0.5g caprolactone to the reaction bottle under anhydrous and oxygen-free conditions The monomer was polymerized at 120°C for 12 hours. After the reaction, the reaction bottle was cooled to room temperature, the toluene was drained, the polymer was dissolved in chloroform, settled with cold methanol, washed, and vacuum-dried to obtain a tri-block PBC copolymer. The polymer 0.5g that obtains is dissolved in the mixed solution of 30ml tetrahydrofuran and methanol (volume ratio is 4: 1) joins in the reactor of 250ml, then adds the hydrogenation reduction catalyst palladium hydroxide / carbon of 0.02g (palladium hydroxide The mass content is 20%), f...

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Abstract

The invention belongs to a biodegradable nano-particle bonded with a hemoglobin molecule, and a method for preparing the biodegradable nano-particle. A polyethylene glycol polyester copolymer with such active functional groups as carboxy groups, amino groups, hydroxyl groups, triple bonds and so on in lateral chains is assembled to form micelle, and the micelle is bonded with the hemoglobin molecule; or firstly, the polyethylene glycol polyester copolymer is bonded with the hemoglobin molecule and then is assembled to get a chemical bonded hemoglobin nano-particle system. The size of the nano-particle prepared ranges from 80nm to 800nm. The hemoglobin accounts for 100 to 500 percent of the nano-particle by weight; the viscosity of the solution ranges from 1MPs to 4MPs; the salt content ranges from 50mM to 200mM; the pH value ranges from 7.0 to 7.6; the oxygen Affinity ranges from 6mmHg to 50mmHg; the stable half life of the hemoglobin ranges from 15 to 24 hours. The bonded hemoglobin nano-particle can be used for manual transmission of oxygen, and as an erythrocyte simulator, which can be used for clinical blood transfusion and to cure cardiovascular and cerebrovascular diseases.

Description

technical field [0001] The invention relates to a biodegradable nano particle bonded with hemoglobin molecules and a preparation method. technical background [0002] As an important means of life saving and maintenance of human body function, blood transfusion has been widely used in clinical practice. However, the traditional blood transfusion measures have great disadvantages. Such as blood type tests are expensive and time-consuming, and it is sometimes difficult to find blood donors with the same blood type; the fresh blood in the hospital can only be stored at 4°C for 3 weeks; the number of blood donors is decreasing day by day, and there is a serious shortage of blood stocks; Yes, viral infections such as HIV, hepatitis viruses, etc. through blood transfusions and other blood products. Therefore, it has become an urgent task to manufacture a safe, efficient, and rapidly applied artificial blood in emergencies. [0003] The red blood cell membrane contains hemoglobi...

Claims

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Application Information

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IPC IPC(8): A61K38/42A61K47/48A61K9/16A61K9/48A61P7/08A61K47/59
Inventor 黄宇彬景遐斌石全吴猛陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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