WO2023050585A1 - 一种医用储氢材料及其制备方法 - Google Patents

一种医用储氢材料及其制备方法 Download PDF

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WO2023050585A1
WO2023050585A1 PCT/CN2021/138059 CN2021138059W WO2023050585A1 WO 2023050585 A1 WO2023050585 A1 WO 2023050585A1 CN 2021138059 W CN2021138059 W CN 2021138059W WO 2023050585 A1 WO2023050585 A1 WO 2023050585A1
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hydrogen storage
storage material
medical
medical hydrogen
ammonia borane
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French (fr)
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王国成
邱实
姚日妹
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中国科学院深圳先进技术研究院
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P39/06—Free radical scavengers or antioxidants

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  • the invention belongs to the field of biomedicine, and relates to a medical hydrogen storage material and a preparation method thereof.
  • H 2 hydrogen gas
  • RANKL Receptor activator of nuclear factor kappa-B ligand
  • the purpose of the embodiments of the present invention is to provide a medical hydrogen storage material and a preparation method thereof, aiming at solving the problem of unstable hydrogen storage.
  • the embodiments of the present invention are realized in the following way, providing a medical hydrogen storage material, which includes a high molecular polymer containing alcoholic hydroxyl groups and ammonia borane and/or its derivatives.
  • the alcoholic hydroxyl group accounts for 30-40% of the total mass of the polymer.
  • the ammonia borane and/or derivatives thereof include amino groups, and the mass of the amino groups accounts for 50%-70% of the total mass of ammonia borane and/or derivatives thereof.
  • the high molecular polymer containing alcoholic hydroxyl groups is polyvinyl alcohol and/or its derivatives.
  • the degree of polymerization of the polyvinyl alcohol is 1700-1900, and the degree of alcoholysis is above 99%.
  • the medical hydrogen storage material also includes magnesium salt.
  • the magnesium salt is selected from one or more of MgCl 2 , MgCO 3 and CH 3 COOMg.
  • the medical hydrogen storage material is prepared to form a film on the surface of the supporting frame, and the supporting frame is preferably polytetrafluoroethylene.
  • Another object of the embodiments of the present invention is to provide a method for preparing a medical hydrogen storage material, which includes the following steps:
  • step S3 also includes adding MgCl 2 .
  • step S3 cleaning with absolute ethanol.
  • the mass of alcoholic hydroxyl groups accounts for 33.3% of the total mass of the polymer; the mass of amino groups accounts for 51.6% of the total mass of ammonia borane and/or its derivatives.
  • the amino groups in ammonia borane and/or its derivatives react with the high molecular polymers containing alcoholic hydroxyl groups, and the amino groups and high molecular polymers form stable chemical bonds to ensure that ammonia borane and / or its derivatives can stably store hydrogen, and are suitable for situations where stable hydrogen release is required in biomedicine.
  • Fig. 1 is the flowchart of the preparation method of medical hydrogen storage material provided by the embodiment of the present invention
  • Fig. 2 is the state before and after the reaction of polyvinyl alcohol and ammonia borane that the embodiment of the present invention provides;
  • Fig. 3 is the hydrogen release capacity of the medical hydrogen storage material added different amounts of ammonia borane provided by the embodiment of the present invention
  • Fig. 4 is the cross-linking degree of film-forming on polytetrafluoroethylene of the medical hydrogen storage material that added different amounts of ammonia borane provided by the embodiment of the present invention
  • Fig. 5 is a graph showing the results of cell proliferation experiments provided by the embodiments of the present invention.
  • Fig. 6 is a graph showing test results of ammonia gas and hydrogen gas released from the medical hydrogen storage material provided by the embodiment of the present invention.
  • NH 3 BH 3 ammonia borane
  • AB ammonia borane
  • the invention provides a medical hydrogen storage material, which enables ammonia borane to have excellent hydrogen storage performance.
  • One embodiment provides a medical hydrogen storage material, which includes a high molecular weight polymer containing alcoholic hydroxyl groups and ammonia borane and/or its derivatives.
  • the mass of alcoholic hydroxyl groups in the high molecular polymer containing alcoholic hydroxyl groups accounts for 30-40% of the total mass of the high molecular polymers containing alcoholic hydroxyl groups.
  • the mass of amino groups in ammonia borane and/or its derivatives accounts for 50-70% of the total mass of ammonia borane and/or its derivatives.
  • the amino groups in ammonia borane and/or its derivatives react with the high molecular polymers containing alcoholic hydroxyl groups, and the amino groups and high molecular polymers form stable chemical bonds to ensure that ammonia borane and / or its derivatives can stably store hydrogen, and are suitable for situations where stable hydrogen release is required in biomedicine.
  • the high molecular polymer containing alcoholic hydroxyl group is polyvinyl alcohol (represented by PVA) and/or its homologues.
  • the degree of polymerization of polyvinyl alcohol is 1700-1900, and the degree of alcoholysis is above 99%.
  • the polymer containing alcoholic hydroxyl groups is polyethylene, and ammonia borane and/or its derivatives are ammonia borane.
  • the medical hydrogen storage material further includes a magnesium salt.
  • the magnesium salt is selected from one or more of MgCl 2 , MgCO 3 and CH 3 COOMg.
  • the present invention also provides a method for preparing medical hydrogen storage materials, comprising the following steps:
  • S2 configured ammonia borane and/or its derivative solution
  • the preparation method of the medical hydrogen storage material provided by the present invention has a simple configuration method and is suitable for large-scale production.
  • the prepared medical hydrogen storage material ensures the hydrogen storage performance of ammonia borane and/or its derivatives, and is suitable for biomedicine.
  • preparation method of medical hydrogen storage material comprises the following steps:
  • S3 further includes adding 100-1000 ⁇ L of MgCl 2 with a concentration of 1 mol/L to 50-200 ⁇ L of the 1 mol/L solution of ammonia borane and/or its derivatives prepared in S2 .
  • MgCl 2 After adding MgCl 2 , the release of ammonia gas from medical hydrogen storage materials is reduced, which can reduce the biotoxicity of medical hydrogen storage materials and make them more suitable for clinical medicine.
  • the mechanism of action is that Mg ions and N atoms form stable complexes , can effectively reduce the amount of N atoms combined with H atoms to form NH 3 .
  • the medical hydrogen storage material also includes:
  • Step 4 Wash the mixture obtained in S3 with absolute ethanol.
  • This step is to clean unreacted high molecular polymers containing alcoholic hydroxyl groups or ammonia borane and/or derivatives thereof.
  • the method for preparing a 6.68*10 -4 mol/L polymer solution containing alcoholic hydroxyl groups in S1 is as follows:
  • the above solvent can be any one of deionized water, ethanol and methanol.
  • the medical hydrogen storage material prepared by the present invention is a flexible jelly.
  • the method for configuring 1mol/L ammonia borane and/or its derivative solution in S2 is as follows:
  • the above solvent can be any one of deionized water, ethanol and methanol.
  • Embodiment 1 Preparation of medical hydrogen storage material
  • the polyvinyl alcohol used in the above examples has a degree of polymerization of 1700 and a degree of alcoholysis of 99%.
  • the mass of ammonia borane in the aqueous solution of ammonia borane added in the preparation process of medical hydrogen storage material 1, medical hydrogen storage material 2 and medical hydrogen storage material 3 were 1.5 mg, 3 mg and 6 mg respectively. During the preparation process of medical material 1, medical material 2 and medical material 3, they were all washed three times with absolute ethanol.
  • Figure A in Figure 2 is the state where the polyvinyl alcohol aqueous solution and the ammonia borane aqueous solution have no cross-linking action
  • Figure B is the state where the polyvinyl alcohol aqueous solution and the ammonia borane aqueous solution have the cross-linking action. It can be seen from Figures A and B that cross-linking can occur when polyvinyl alcohol aqueous solution is mixed with ammonia borane aqueous solution, and a colloidal substance is generated from a liquid state.
  • Embodiment 2 Hydrogen release test of medical hydrogen storage material
  • the hydrogen release amount of the medical hydrogen storage material increases.
  • Embodiment 3 Observation of the film morphology of medical hydrogen storage material
  • Step 1 Prepare the medical hydrogen storage material 1, the medical hydrogen storage material 2 and the medical hydrogen storage material 3 on polytetrafluoroethylene to form a film.
  • the second step observe the surface of the medical hydrogen storage material sprayed with gold with a field emission scanning electron microscope.
  • Figure A shows the degree of cross-linking of medical hydrogen storage material 1
  • Figure B shows the degree of cross-linking of medical hydrogen storage material 2
  • Figure C shows the degree of cross-linking of medical hydrogen storage material 3.
  • Polyvinyl alcohol film preparation of medical hydrogen storage material 2, polyvinyl alcohol aqueous solution, ammonia borane aqueous solution and MgCl 2 in medical hydrogen storage material 5
  • Step 1 Filter and sterilize the polyvinyl alcohol aqueous solution and the ammonia borane aqueous solution in the prepared medical hydrogen storage material 2 and medical hydrogen storage material 5 respectively, and form a film on the surface of the 0.22 ⁇ m polytetrafluoroethylene membrane.
  • Step 2 After drying the membranes of medical hydrogen storage material 2 and medical hydrogen storage material 5 at 60°C, place them on a 24-well cell culture plate, and set 3 parallel samples of experimental groups for each medical hydrogen storage material. At the same time, a blank group and a control group were set up, the control group was added with polyvinyl alcohol film or 0.22 ⁇ m polytetrafluoroethylene film, and one sample was set for each, and the blank group was a 24-well culture plate.
  • Step 3 Inoculate 2*10 4 MC3T3-E1 cells on the experimental group, control group and blank group, and inoculate the MC3T3-E1 cells for 4 hours in a carbon dioxide incubator.
  • Step 4 Use a multi-channel pipette to pipette one tenth of the medium volume of CCK-8 reagent and add it to the experimental group, control group and blank group, and cultivate for another 0.5-4 hours.
  • Step 5 Use a microplate reader to measure the absorbance at 450nm of each experimental group, control group and blank group.
  • Figure 5 shows the 450nm absorbance of the experimental group, the control group and the blank group over time, the greater the absorbance, the greater the number of MC3T3-E1 cells.
  • the experimental group marked as orifice plate is the blank group
  • the control group marked as filter membrane is added with 0.22 ⁇ m polytetrafluoroethylene membrane
  • the experimental group marked as PVA filter membrane is added with polyvinyl alcohol membrane, marked as PVA+
  • the experimental group of AB filter membrane added the membrane made of medical hydrogen storage material 2
  • the experimental group marked as PVA+AB+MgCl 2 filter membrane added the membrane made of medical hydrogen storage material 5.
  • control group with 0.22 ⁇ m polytetrafluoroethylene membrane showed that the addition of 0.22 ⁇ m polytetrafluoroethylene membrane was beneficial to the proliferation of MC3T3-E1 cells.
  • control group added with 0.22 ⁇ m polytetrafluoroethylene membrane Compared with the control group added with 0.22 ⁇ m polytetrafluoroethylene membrane, the control group added with polyvinyl alcohol membrane and 0.22 ⁇ m tetrafluoroethylene membrane had more MC3T3-E1 cells on the first day and the fifth day, and in the third day The number of days is slightly less. Overall, the addition of polyvinyl alcohol film is beneficial to the proliferation of MC3T3-E1 cells.
  • the MC3T3-E1 of the experimental group adding polyvinyl alcohol film, ammonia borane, MgCl 2 and 0.22 ⁇ m polytetrafluoroethylene film
  • the number of cells increased significantly, indicating that the addition of MgCl 2 can significantly inhibit the release of ammonia in the medical hydrogen storage material 2 and reduce biological toxicity.
  • the number of MC3T3-E1 cells in the experimental group with 0.22 ⁇ m polytetrafluoroethylene membrane tended to decrease on the first day and the third day, but the difference was not significant. On the fifth day, the number of MC3T3-E1 cells was more than that of other blank groups and controls Group.
  • Embodiment 5 release ammonia, hydrogen test of medical hydrogen storage material
  • Step 1 Prepare medical hydrogen storage material 2, medical hydrogen storage material 4, medical hydrogen storage material 5 and medical hydrogen storage material 6 on 0.22 ⁇ m polytetrafluoroethylene to form a film.
  • the second step use the "National Environmental Protection Standard of the People's Republic of China HJ535-2009" and Nessler's reagent to test the release of ammonia gas from the membranes of the above medical hydrogen storage materials.
  • Step 3 Use a hydrogen-rich water test pen to test the amount of hydrogen released by the membranes of the above medical hydrogen storage materials in ultrapure water.
  • Figure A is the content of hydrogen released over time from the films of medical hydrogen storage material 2, medical hydrogen storage material 4, medical hydrogen storage material 5 and medical hydrogen storage material 6;
  • Figure B is medical hydrogen storage The refractive index of the films of material 2, medical hydrogen storage material 4, medical hydrogen storage material 5 and medical hydrogen storage material 6 over time, the greater the refractive index, the greater the ammonia gas content.
  • AB is the medical hydrogen storage material 2
  • AB+100 ⁇ L 1M MgCl 2 is the medical hydrogen storage material 4
  • AB+500 ⁇ L 1M MgCl 2 is the medical hydrogen storage material
  • AB+1000 ⁇ L 1M MgCl 2 is the medical hydrogen storage material 6
  • medical hydrogen storage material 4 Compared with medical hydrogen storage material 2 without adding MgCl 2 , medical hydrogen storage material 4 has a smaller decrease in the amount of hydrogen released in the first 24 hours, and the amount of released hydrogen in the 36th hour is the same. volume decreased slightly.
  • the medical hydrogen storage material 4 can suppress the generation of ammonia gas in the first 24 hours, and basically has no inhibitory effect on the generation of ammonia gas after 36 hours.
  • the amount of hydrogen released in the first 36 hours is about half of that released by the medical hydrogen storage material 2, and the amount of hydrogen released in the 48th hour Increased, but still lower than the hydrogen release of medical hydrogen storage material 2.
  • the medical hydrogen storage material 5 has a lower hydrogen release rate than the medical hydrogen storage material 4 in each time period.
  • medical hydrogen storage material 6 Compared with medical hydrogen storage material 2, medical hydrogen storage material 4, and medical hydrogen storage material 5 without adding MgCl2 , medical hydrogen storage material 6 has the least amount of hydrogen released in each time period.
  • medical hydrogen storage materials 5 and 6 can significantly inhibit the formation of ammonia gas in the first 24 hours, and have no obvious inhibitory effect on the formation of ammonia gas after 36 hours.
  • medical hydrogen storage materials 5 and 6 have a stronger ability to suppress ammonia gas generation in the first 24 hours.
  • the ability to suppress the generation of ammonia is equal.
  • adding a small amount of MgCl in the medical hydrogen storage material has a small inhibitory effect on the generation of ammonia, and at the same time, has little effect on the amount of hydrogen released, especially within 24 hours. .
  • the inhibitory effect on ammonia gas generation is obviously enhanced, but hydrogen gas generation is also slightly affected.
  • the addition of MgCl 2 increases to a certain extent, the inhibitory effect on the formation of ammonia is not enhanced, and the release of hydrogen will be further reduced.
  • the medical hydrogen storage material provided by the invention has a stable hydrogen storage capacity, and at the same time, due to the cross-linking reaction between the ammonia borane and polyvinyl alcohol, it can reduce the release of ammonia gas and reduce the biological toxicity of the ammonia borane.
  • the amount of polyvinyl alcohol is determined, the more the amount of ammonia borane reacted with it, the better the hydrogen storage capacity of the medical hydrogen storage material.
  • the present invention also provides a medical hydrogen storage material containing magnesium chloride. In the case of adding an appropriate amount of magnesium chloride, the hydrogen storage capacity of the medical hydrogen storage material does not decrease significantly, but the release of ammonia gas is further reduced, which has better performance. Biosafety, suitable for the field of medicine.

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Abstract

一种医用储氢材料及其制备方法，适用于生物医用领域。医用储氢材料包括含有醇羟基的高分子聚合物和氨硼烷和/或其衍生物。医用储氢材料中，氨硼烷和/或其衍生物中的氨基与含有醇羟基的高分子聚合物反应，氨基和高分子聚合物形成稳定的化学键，保证氨硼烷和/或其衍生物能够稳定储氢，适用于生物医药中需要稳定释氢的情形。

Description

一种医用储氢材料及其制备方法 技术领域
本发明属于生物医用领域，涉及一种医用储氢材料及其制备方法。
背景技术
在生物医药领域，氢气(H 2)是一种有效的抗氧化剂，由于其具有在膜上迅速扩散的能力，它可以到达细胞并与具有细胞毒性的ROS反应，防止氧化损伤[Ohsawa I,Ishikawa M,Takahashi K,et al.Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals[J].Nature medicine,2007,13(6):688.]。不仅如此，H 2对M1型巨噬细胞的增殖有明显的抑制作用，还能阻止RANKL(Receptor activator of nuclear factor kappa-B ligand)诱导的相关破骨细胞分化，达到抗炎促成骨的作用。然而，H 2在目前的应用过程中存在问题，如不易存储等问题，导致其在生物医药领域受到限制。
因此，亟需一种可以稳定储氢的医用储氢材料。
发明内容
本发明实施例的目的在于提供一种医用储氢材料及其制备方法，旨在解决储氢不稳定的问题。
本发明实施例是这样实现的，提供了一种医用储氢材料，该医用储氢材料包括含有醇羟基的高分子聚合物和氨硼烷和/或其衍生物。
优选地，所述醇羟基的质量占高分子聚合物总质量的30-40％。
优选地，所述氨硼烷和/或其衍生物包括氨基，所述氨基的质量占氨硼烷和/或其衍生物总质量的50％-70％。
优选地，所述含有醇羟基的高分子聚合物为聚乙烯醇和/或其衍生物。
进一步地，所述聚乙烯醇的聚合度为1700-1900，醇解度为99％以上。
进一步地，医用储氢材料还包括镁盐。
所述镁盐选自MgCl 2、MgCO 3及CH 3COOMg中的一种或多种。
进一步地，所述医用储氢材料制备于支撑骨架表面成膜，所述支撑骨架优选聚四氟乙烯。
本发明实施例的另一目的在于提供医用储氢材料的制备方法，所述医用储氢材料的制备方法包括以下步骤：
S1：配置含有醇羟基的高分子聚合物溶液；
S2：配置氨硼烷和/或其衍生物溶液；
S3：取以上步骤S2中配置的氨硼烷和/或其衍生物溶液，加入以上步骤S1中配置的含有醇羟基的高分子聚合物溶液，混合反应。
进一步地，步骤S3中还包括加入MgCl 2。
进一步地，步骤S3之后，还包括步骤S4：用无水乙醇清洗。
优选地，醇羟基的质量占高分子聚合物总质量的33.3％；氨基的质量占氨硼烷和/或其衍生物总质量的51.6％。
在本发明提供的医用储氢材料中，氨硼烷和/或其衍生物中的氨基与含有醇羟基的高分子聚合物反应，氨基和高分子聚合物形成稳定的化学键，保证氨硼烷和/或其衍生物能够稳定储氢，适用于生物医药中需要稳定释氢的情形。
附图说明
图1是本发明实施例提供的医用储氢材料的制备方法的流程图；
图2是本发明实施例提供的聚乙烯醇和氨硼烷反应前后的状态；
图3是本发明实施例提供的添加了不同量的氨硼烷的医用储氢材料的释氢能力；
图4是本发明实施例提供的添加了不同量的氨硼烷的医用储氢材料的在聚四氟乙烯上成膜的交联程度；
图5是本发明实施例提供的细胞增殖实验结果图；
图6是本发明实施例提供的医用储氢材料的释放氨气、氢气测试结果图。
具体实施方式
为了使本发明要解决的技术问题、技术方案及有益效果更加清楚明白，以下结合附图及实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
氨硼烷(NH 3BH 3，用AB表示)分子的质量和储氢密度分别高达19.6wt％和153g/L，是一种非常优秀的储氢材料，多用于能源储氢，如应用于燃料电池。NH 3BH 3储存和释放氢气不稳定，制约了其在生物医用领域的应用。
本发明提供了一种医用储氢材料，使氨硼烷具备优秀的储氢性能。
一个实施例提供了一种医用储氢材料，包括含有醇羟基的高分子聚合物和氨硼烷和/或其衍生物。
具体地，含有醇羟基的高分子聚合物中醇羟基的质量占含有醇羟基的高分子聚合物总质量的30-40％。
具体地，氨硼烷和/或其衍生物中氨基的质量占氨硼烷和/或其衍生物的总质量的50-70％。
在本发明提供的医用储氢材料中，氨硼烷和/或其衍生物中的氨基与含有醇羟基的高分子聚合物反应，氨基和高分子聚合物形成稳定的化学键，保证氨硼烷和/或其衍生物能够稳定储氢，适用于生物医药中需要稳定释氢的情形。
进一步地，含有醇羟基的高分子聚合物为聚乙烯醇(用PVA表示)和/或其同系物。
优选地，聚乙烯醇的聚合度为1700-1900，醇解度为99％以上。
在一个实施例中，含有醇羟基的高分子聚合物为聚乙烯，氨硼烷和/或其衍生物为氨硼烷。
在另一个实施例中，医用储氢材料还包括镁盐。镁盐选自MgCl 2、MgCO 3及CH 3COOMg中的一种或多种。
请参与图1，本发明还提供了一种医用储氢材料的制备方法，包括以下步骤：
S1：配置含有醇羟基的高分子聚合物溶液；
S2：配置的氨硼烷和/或其衍生物溶液；
S3：取S2中配置的氨硼烷和/或其衍生物溶液，加入S1中配置的含有醇羟基的高分子聚合物溶液混合均匀。
本发明提供的医用储氢材料的制备方法配置方法简单，适用于大规模生产，制备的医用储氢材料保证氨硼烷和/或其衍生物的储氢性能，适用于生物医药。
进一步地，医用储氢材料的制备方法，包括以下步骤：
S1：配置6.68*10 -4mol/L含有醇羟基的高分子聚合物溶液；
S2：配置1mol/L的氨硼烷和/或其衍生物溶液；
S3：取50-200μL S2中配置的1mol/L的氨硼烷和/或其衍生物溶液，加入1ml S1中配置的6.68*10 -4mol/L含有醇羟基的高分子聚合物溶液混合均匀。
在一个实施例中，S3还包括向50-200μL S2中配置的1mol/L的氨硼烷和/或其衍生物溶液中加入100-1000μL浓度为1mol/L的MgCl 2。
加入MgCl 2后，医用储氢材料的氨气的释放量减少，能够降低医用储氢材料的生物毒性，使其更适合应用于临床医学，其作用机理为Mg离子和N原子形成稳定络合物，能够有效减少N原子结合H原子形成NH 3的量。
在一个实施例中，医用储氢材料中还包括：
步骤4：用无水乙醇对S3中取得的混合物进行清洗。
此步骤的目的在于将未反应的含有醇羟基的高分子聚合物或氨硼烷和/或其衍生物清洗。
在一个实施例中，S1中配置6.68*10 -4mol/L含有醇羟基的高分子聚合物溶液的方法如下：
在20mL溶剂中加入0.023mol聚乙烯醇，并加入磁力搅拌子搅拌，加热至90℃，持续搅拌直至完全溶解，其中，聚乙烯醇的聚合度为1700，醇解度为99％。
上述溶剂可为去离子水、乙醇和甲醇中的任一种。
本发明制备的医用储氢材料为柔性胶状物，聚乙烯醇的聚合度越大，医用储氢材料的交联度越高，硬度越大。
在一个实施例中，S2中配置1mol/L的氨硼烷和/或其衍生物溶液的方法如下：
在10mL溶剂中加入0.01mol氨硼烷，搅拌溶解。
上述溶剂可为去离子水、乙醇和甲醇中的任一种。
下面通过具体医用储氢材料的具体实验实施例来对本发明作进一步的阐述。
实施例1医用储氢材料的制备
Figure PCTCN2021138059-appb-000001
Figure PCTCN2021138059-appb-000002
以上实施例中使用的聚乙烯醇的聚合度为1700，醇解度为99％。
医用储氢材料1、医用储氢材料2及医用储氢材料3制备过程中添加的氨硼烷的水溶液中的氨硼烷的质量分别为1.5mg、3mg及6mg。医用材料1、医用材料2及医用材料3制备过程中均用无水乙醇清洗三遍。
请参阅图2，图2中的图A为聚乙烯醇水溶液与氨硼烷水溶液未发生交联作用的状态，图B为聚乙烯醇水溶液与氨硼烷水溶液发生交联作用的状态。从图A和图B中可以看出，聚乙烯醇水溶液与氨硼烷水溶液混合能够发生交联，由液态生成胶状物质。
实施例2医用储氢材料氢气释放测试
2.1材料
医用储氢材料1、医用储氢材料2及医用储氢材料3
2.2实验仪器
富氢水测试笔
2.3实验步骤
将医用储氢材料1、医用储氢材料2及医用储氢材料3放置在超纯水，用富氢水测试笔测试医用储氢材料的氢气释放量。
2.4结果
如图3所示，医用储氢材料3的氢气释放量>医用储氢材料2的氢气释放量>医用储氢材料3的氢气释放量。
2.5结论
随着医用储氢材料制备过程中添加的氨硼烷的质量的增加，医用储氢材料的氢气释放量增大。
实施例3医用储氢材料膜形貌的观察
3.1材料
膜厚为0.22μm聚四氟乙烯膜、制备医用储氢材料1、医用储氢材料2、医用储氢材料3过程中的聚乙烯醇水溶液及氨硼烷水溶液
3.2实验仪器
场发射扫描电镜
3.3实验步骤
第一步：将医用储氢材料1、医用储氢材料2及医用储氢材料3制备在聚四氟乙烯成为膜状。
第二步：用场发射扫描电镜观察经喷金后的医用储氢材料表面。
3.4结果
如图4所示，图A为医用储氢材料1的交联程度，图B为医用储氢材料2的交联程度，图C为医用储氢材料3的交联程度。
3.5结论
随着医用储氢材料制备过程中添加的氨硼烷的质量的增加，医用储氢材料的交联程度增大。
实施例4膜医用材料的细胞增殖实验
4.1材料
聚乙烯醇膜、制备医用储氢材料2、医用储氢材料5中的聚乙烯醇水溶液、氨硼烷水溶液及MgCl 2
4.2实验仪器
0.22μm聚四氟乙烯膜、24孔细胞培养板、MC3T3-E1细胞、多孔道移液器、带有450nm滤光片的酶标仪、二氧化碳培养箱及Cell counting Kit-8(简称CCK-8)试剂
4.3实验步骤
第一步：将制备医用储氢材料2及医用储氢材料5中的聚乙烯醇水溶液及氨硼烷水溶液分别经滤膜过滤杀菌，在0.22μm聚四氟乙烯膜表面成膜。
第二步：将医用储氢材料2及医用储氢材料5的膜在60℃干燥后，置于24孔细胞培养板上，每种医用储氢材料设置3个实验组平行样品。同时，设置空白组和对照组，对照组添加聚乙烯醇膜或0.22μm聚四氟乙烯膜，各设置一个样品，空白组为24孔培养板。
第三步：实验组、对照组及空白组上接种2*10 4个MC3T3-E1细胞，接种MC3T3-E1细胞后在二氧化碳培养箱培养4个小时。
第四步：用多孔道移液器移取培养基体积十分之一的CCK-8试剂添加到设置实验组、对照组及空白组，再培养0.5-4个小时。
第五步：使用酶标仪测定各设置实验组、对照组及空白组450nm吸光度。
4.4结果
如图5所示，图5为随时间的推移实验组、对照组及空白组的450nm吸光度，吸光度越大，MC3T3-E1细胞的数量越多。图中，标记为孔板的实验组为空白组，标记为滤膜的对照组添加了0.22μm聚四氟乙烯膜，标记为PVA滤膜的实验组添加了聚乙烯醇膜，标记为PVA+AB滤膜的实验组添加了医用储氢材料2制备的膜，标记为PVA+AB+MgCl 2滤膜的实验组添加了医用储氢材料5制备的膜。
4.5结论
和空白组孔板相比，加入0.22μm聚四氟乙烯膜的对照组显示，0.22μm聚四氟乙烯膜的加入有利于MC3T3-E1细胞的繁殖。
和加入0.22μm聚四氟乙烯膜的对照组相比，加入聚乙烯醇膜和0.22μm四氟乙烯膜的对照组在第一天和第五天MC3T3-E1细胞的数量更多，在第三天的数量稍少。总体上，加入聚乙烯醇膜有利于MC3T3-E1细胞的繁殖。
和加入聚乙烯醇膜和0.22μm聚四氟乙烯膜的对照组相比，加入聚乙烯醇 膜、氨硼烷和0.22μm四氟乙烯膜的实验组的MC3T3-E1细胞的数量明显下降，证明氨硼烷在产生氢气的过程释放的氨气具有细胞毒性，不利于MC3T3-E1细胞的繁殖。
和加入聚乙烯醇膜、氨硼烷和0.22μm四氟乙烯膜的实验组相比，加入聚乙烯醇膜、氨硼烷、MgCl 2和0.22μm聚四氟乙烯膜的实验组的MC3T3-E1细胞的数量明显上升，说明加入MgCl 2能够明显抑制医用储氢材料2中的氨气释放量，降低生物毒性。
和空白组孔板、加入0.22μm聚四氟乙烯膜的对照组和加入聚乙烯醇膜和0.22μm聚四氟乙烯膜的对照组相比，加入聚乙烯醇膜、氨硼烷、MgCl 2和0.22μm聚四氟乙烯膜的实验组在第一天及第三天MC3T3-E1细胞的数量有下降趋势，但是相差不大，在第五天MC3T3-E1细胞的数量多于其他空白组及对照组。
实施例5医用储氢材料的释放氨气、氢气测试
5.1材料
0.22μm四氟乙烯膜、制备医用储氢材料2、医用储氢材料4、医用储氢材料5、医用储氢材料6过程中的聚乙烯醇水溶液、氨硼烷水溶液及MgCl 2
5.2实验仪器
纳氏试剂及富氢水测试笔
5.3实验步骤
第一步：将医用储氢材料2、医用储氢材料4、医用储氢材料5及医用储氢材料6制备在0.22μm聚四氟乙烯上成膜。
第二步：采用《中华人民共和国国家环境保护标准HJ535-2009》及纳氏试剂测试以上各医用储氢材料的膜氨气的释放量。
第三步：采用富氢水测试笔测试以上各医用储氢材料的膜在超纯水中的氢气释放量。
5.4结果
如图6所示，图A为医用储氢材料2、医用储氢材料4、医用储氢材料5及医用储氢材料6的膜的随时间的推移释放氢气的含量；图B为医用储氢材料2、医用储氢材料4、医用储氢材料5及医用储氢材料6的膜的随时间的折光率，折光率越大，氨气的含量越大。图5中，AB为医用储氢材料2，AB+100μL 1M MgCl 2为医用储氢材料4，AB+500μL 1M MgCl 2为医用储氢材料5，AB+1000μL 1M MgCl 2为医用储氢材料6
5.5结论
医用储氢材料4和未添加MgCl 2的医用储氢材料2相比，在前24小时内释放氢气的量下降程度变小，在第36小时释放氢气的量持平，在第48小时释放氢气的量有小幅度下降。
医用储氢材料4和未添加MgCl 2的医用储氢材料2相比，在前24个小时能够抑制氨气的生成量，在36个小时以后基本对氨气的生成基本没有抑制作用。
医用储氢材料5和未添加MgCl 2的医用储氢材料2相比，在前36个小时内释放氢气的量为医用储氢材料2释放氢气量的一半左右，在第48小时释放氢气的量增加，但仍低于医用储氢材料2的氢气释放量。医用储氢材料5和医用储氢材料4相比，在各个时间段均低于医用储氢材料4的氢气释放量。
医用储氢材料6和未添加MgCl 2的医用储氢材料2、医用储氢材料4、医用储氢材料5相比，各时间段的氢气释放量都是最少的。
医用储氢材料5、6和未添加MgCl 2的医用储氢材料2相比，在前24个小时能够明显抑制氨气的生成，在第36个小时以后对氨气的生成没有明显抑制作用。医用储氢材料5、6和医用储氢材料4相比，在前24个小时，抑制氨气生成的能力较强。医用储氢材料5和医用储氢材料6相比，抑制氨气生成的能力持平。
因此，在医用储氢材料中添加少量的MgCl 2的对氨气的生成具有较小的抑制作用，同时，对氢气释放量影响较小，尤其是在24小时内对氢气的释放量影 响较小。随着MgCl 2添加量的增加，对氨气生成的抑制作用明显增强，但是氢气的生成也有轻微的影响。当MgCl 2添加量增加大到一定程度后，对氨气的生成的抑制作用没有增强，而且会进一步降低氢气的释放量。
本发明提供的医用储氢材料具有稳定的储氢能力，同时由于氨硼烷和聚乙烯醇发生交联反应，能够降低氨气的释放量，降低氨硼烷的生物毒性。在聚乙烯醇物质的量确定的情况下，与其反应的氨硼烷的物质的量越多，医用储氢材料的储氢能力越好。在此基础上，本发明还提供了包含氯化镁的医用储氢材料，在添加适量氯化镁的情况下，医用储氢材料的储氢能力没有明显下降，但是氨气的释放量进一步减少，具有更好的生物安全性，适用于医药领域。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。

Claims (10)

  1. 一种医用储氢材料，其特征在于，包括含有醇羟基的高分子聚合物和氨硼烷和/或其衍生物。
  2. 如权利要求1所述的医用储氢材料，其特征在于，醇羟基的质量占高分子聚合物总质量的30-40％；
    氨基的质量占氨硼烷和/或其衍生物总质量的50-70％。
  3. 如权利要求1所述的医用储氢材料，其特征在于，所述含有醇羟基的高分子聚合物为聚乙烯醇和/或其衍生物。
  4. 如权利要求3所述的医用储氢材料，其特征在于，所述聚乙醇的聚合度为1700-1900，醇解度为99％以上。
  5. 如权利要求1或3所述的医用储氢材料，其特征在于，还包括镁盐。
  6. 如权利要求5所述的医用储氢材料，其特征在于，所述医用储氢材料制备于支撑骨架表面成膜。
  7. 一种医用储氢材料的制备方法，其特征在于，包括以下步骤：
    S1：配置含有醇羟基的高分子聚合物溶液；
    S2：配置的氨硼烷和/或其衍生物溶液；
    S3：取步骤S2中配置的氨硼烷和/或其衍生物溶液，加入步骤S1中配置的含有醇羟基的高分子聚合物溶液，混合反应。
  8. 如权利要求7所述的医用储氢材料的制备方法，其特征在于，步骤S3中还包括加入MgCl 2。
  9. 如权利要求7所述的医用储氢材料的制备方法，其特征在于，还包括S4：用无水乙醇清洗。
  10. 如权利要求7或8所述的医用储氢材料的制备方法，其特征在于，醇羟基的质量占高分子聚合物总质量的33.3％；
    氨基的质量占氨硼烷和/或其衍生物总质量的51.6％。
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