Phase change hydrogel and manufacturing method thereof

Abstract

The invention provides a phase change hydrogel and a preparation method thereof. The phase change hydrogel provided by the invention comprises a hydrogel and a phase change microcapsule dispersed in the hydrogel. The phase-change hydrogel can provide stable temperature in the organ storage process, the influence of temperature fluctuation on organs is reduced, and therefore the transplantation success rate is increased. In addition, the phase-change hydrogel does not need external power supply and is simple and portable, and the phase-change material can be recycled.

Description

Technical Field

[0001] The invention relates to a phase-change hydrogel and a manufacturing method thereof, and belongs to the field of polymer materials. Background Art

[0002] Currently, organ transplantation (such as kidney transplantation) is one of the main methods for treating organ failure. However, during the process of removing an organ (such as a kidney) from a donor and transplanting it into a recipient, the organ needs to be stored at an appropriate temperature to ensure that it maintains its functional state.

[0003] Traditional organ preservation methods mainly rely on refrigeration or freezing, but these methods often fail to provide stable and uniform organ storage conditions. This is because they rely on the external ambient temperature and are susceptible to temperature fluctuations. In addition, even with the use of an incubator, it is difficult to ensure that the temperature is evenly distributed throughout the organ. This may lead to abnormal temperatures in some areas of the organ, affecting the organ's quality or causing possible damage to the organ, limiting the success rate of transplantation.

[0004] Although there are literatures involving the use of phase change materials to improve organ storage methods, these materials usually exist in solid form, and solid phase change makes it difficult to solve the problem of uniform dispersion of phase change materials. Therefore, in liquid carriers, phase change microcapsules may deposit or aggregate, resulting in uneven temperature distribution. This may cause problems of too high or too low temperatures for organs. In addition, traditional insulation methods must rely on external power supply, resulting in the inability to provide the stable temperature conditions required for a long time during the transplant process. This is especially important when it takes a long time to wait for the transplant surgery. Unstable temperature may cause damage to the organ or loss of transplantability.

[0005] In addition, some existing phase change materials may release harmful substances, causing potential damage to organs and fail to meet the biocompatibility requirements of medical organ insulation materials, which may affect the survival and function of organs after transplantation.

[0006] Therefore, a new technology is needed to store transplant organs more efficiently and improve the success rate of organ transplantation. Summary of the invention

[0007] Problem that the invention aims to solve

[0008] The present invention is made to solve the above-mentioned existing problems, and its purpose is to provide a phase change hydrogel and a method for producing the same.

[0009] Solutions for solving problems

[0010] The present inventors have conducted intensive studies to solve the above-mentioned problems and have found that the above-mentioned problems can be solved by introducing phase-change microcapsules having a fixed melting point into a hydrogel, thereby completing the present invention.

[0011] That is, the present invention is as follows.

[0012] [1]. A phase change hydrogel, comprising: a hydrogel, and phase change microcapsules dispersed in the hydrogel.

[0013] [2] The phase-change hydrogel according to [1], wherein the content of the phase-change microcapsules is 10 to 80% of the content of the hydrogel.

[0014] [3] The phase change hydrogel according to [1] or [2], wherein the hydrogel comprises a first composition and a second composition;

[0015] The first composition comprises chitosan, an electrolyte, and a solvent selected from at least one of water and a buffer solution;

[0016] The second composition comprises alginate, an aldehyde-terminated polymer and water.

[0017] [4] The phase change hydrogel according to [3], characterized in that in the first composition, the content of the chitosan is 0.9 to 10% by mass relative to the total amount of the first composition;

[0018] In the first composition, the content of the electrolyte is 0.1 to 1 mass % relative to the total amount of the first composition;

[0019] In the first composition, the content of the buffer solution or water is 20 to 99% by mass relative to the total amount of the first composition;

[0020] In the second composition, the content of the alginate is 0.9 to 10% by mass relative to the total amount of the second composition;

[0021] In the second composition, the content of the aldehyde-terminated polymer is 0.09 to 10% by mass relative to the total amount of the second composition;

[0022] In the second composition, the content of water is 20 to 99% by mass relative to the total amount of the second composition;

[0023] The chitosan comprises ethylene glycol chitosan, hydroxyethyl chitosan or carboxymethyl chitosan;

[0024] The electrolyte comprises calcium sulfate, calcium lactate, calcium hydrogen phosphate or calcium chloride;

[0025] The alginate comprises sodium alginate or potassium alginate;

[0026] The aldehyde-terminated polymer comprises aldehyde-terminated polyethylene glycol, aldehyde-terminated polyacrylic acid, aldehyde-terminated vinyl alcohol or dialdehyde-terminated polyethylene glycol diester.

[0027] [5] The phase change hydrogel according to [1] or [2], wherein the average particle size of the phase change microcapsules is 2 to 3 μm;

[0028] The phase-change microcapsule has a core-shell structure.

[0029] [6] A method for preparing a phase change hydrogel according to any one of [1] to [5], the method comprising:

[0030] Preparation of phase change microcapsules; and

[0031] Preparation process of phase change hydrogel,

[0032] Wherein, the process of preparing phase change hydrogel comprises:

[0033] The process of preparing the first solution is as follows: dissolving chitosan and electrolyte in water or a buffer solution to obtain the first solution;

[0034] The process of preparing the second liquid is as follows: dissolving alginate and aldehyde-terminated polymer in water, and adding the phase change microcapsules to obtain the second liquid;

[0035] The process of preparing the phase-change hydrogel is as follows: the first liquid and the second liquid are mixed and introduced into a mold for forming to obtain the phase-change hydrogel.

[0036] [7] The preparation method according to [6], wherein the step of preparing phase change microcapsules comprises:

[0037] Step A: mixing a phase change material, a silane precursor, a polymerization monomer and an initiator;

[0038] Step B: dispersing the mixture obtained in the above step A in an aqueous solution containing an emulsifier for emulsification to obtain an emulsion;

[0039] Step C: subjecting the emulsion obtained in the above step B to polymerization reaction to obtain phase change microcapsules.

[0040] [8] The preparation method according to [7], wherein the phase change material comprises paraffin;

[0041] The silane precursor comprises two or more of tetraethyl orthosilicate, methyl orthosilicate, aminopropyltriethoxysilane, octadecyltrimethoxysilane and propyltrimethoxysilane methacrylate;

[0042] The polymerizable monomer comprises at least one of styrene, divinylbenzene and ethylene glycol dimethacrylate;

[0043] The initiator comprises at least one of dibenzoyl peroxide, dodecyl peroxide, tert-butyl peroxyvalerate, diisopropyl peroxydicarbonate, diisopropyl peroxide, azobisisobutyronitrile and azobisisoheptylonitrile;

[0044] The emulsifier comprises at least one of styrene-maleic anhydride copolymer aqueous solution, hexadecyltrimethylammonium bromide, sodium lauryl sulfate, Tween 80, sodium lauryl sulfate, polyoxyethylene ether sorbitan monooleate, and sorbitan monooleate.

[0045] [9] The preparation method according to [6] or [7], wherein the step of preparing the first liquid satisfies at least one of the following:

[0046] (a) in the first liquid, the content of the chitosan is 0.9 to 10% by mass relative to the total amount of the first liquid;

[0047] (b) in the first liquid, the content of the electrolyte is 0.1 to 1 mass % relative to the total amount of the first liquid;

[0048] (c) the content of water or buffer solution is 20 to 99% by mass relative to the total amount of the first liquid;

[0049] (d) the buffer solution is a sodium bicarbonate buffer solution;

[0050] (e) the chitosan comprises ethylene glycol chitosan, hydroxyethyl chitosan or carboxymethyl chitosan;

[0051] (f) the electrolyte comprises calcium sulfate, calcium lactate, calcium hydrogen phosphate or calcium chloride;

[0052] The process of preparing the second liquid satisfies at least one of the following:

[0053] (g) in the second liquid, the content of the alginate is 0.9 to 10% by mass relative to the total amount of the second liquid;

[0054] (h) in the second liquid, the content of the aldehyde-terminated polymer is 0.09 to 10% by mass relative to the total amount of the second liquid;

[0055] (i) in the second liquid, the content of water is 20 to 99% by mass relative to the total amount of the second liquid;

[0056] (j) the alginate comprises sodium alginate or potassium alginate;

[0057] (m) The aldehyde-terminated polymer comprises aldehyde-terminated polyethylene glycol, aldehyde-terminated polyacrylic acid, aldehyde-terminated vinyl alcohol or dialdehyde-terminated polyethylene glycol diester.

[0058]

[10] . Use of the phase change hydrogel according to any one of [1] to [5] in the preparation of thermal insulation materials for organ transplant surgery.

[0059] Effects of the Invention

[0060] The present invention aims to solve the problems of unstable temperature, uneven temperature, poor biocompatibility and other problems existing in the prior art of organ (such as kidney) transplantation surgery, and proposes a phase change hydrogel based on phase change microcapsules. Through the application of phase change microcapsule double network hydrogel, the present invention achieves the following effects:

[0061] (1) Stable organ temperature preservation conditions: The present invention introduces phase-change microcapsules to enable the organ to maintain a stable temperature during the entire transplantation storage process. Phase-change microcapsules absorb and release heat within a specific temperature range, achieving a constant temperature state for the organ, effectively solving the problem of temperature instability, and is suitable for transplantation operations that require a long waiting time.

[0062] (2) Uniform temperature distribution: By uniformly dispersing phase change microcapsules in the hydrogel to form a double network structure, the present invention achieves better temperature distribution, which helps to avoid local temperature anomalies, improve the overall quality and survival rate of organs, and solve the uneven temperature problem in the prior art.

[0063] (3) The temperature of the phase-change microcapsules is controllable, and portable phase-change hydrogels with specific cold or heat sources can be prepared. The double-network hydrogel has good ductility while ensuring good mechanical properties, which can achieve good coverage of the kidneys and ensure uniform temperature distribution. The part of the phase-change microcapsule particles exposed in the network has polar reactive groups, which can not only give the hydrogel multiple phase-change temperatures, but also provide rich functional expansion sites, giving the present invention a broad application prospect. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] Figure 1 This is a scanning electron microscope image of the phase change microcapsules obtained in Example 1.

[0065] Figure 2 This is a cryo-scanning electron microscopy image of the phase change hydrogel obtained in Example 1.

[0066] Figure 3 This is a diagram showing the phase change hydrogel prepared in Example 1 wrapping a pig kidney.

[0067] Figure 4 This is the temperature rise curve of the temperature control experiment in Example 1.

[0068] Figure 5 This is a scanning electron microscope image of the hydrogel obtained in Comparative Example 1.

[0069] Figure 6 This is a diagram showing the hydrogel prepared in Comparative Example 1 encapsulating a pig kidney.

[0070] Figure 7 This is the temperature rise curve of the temperature control experiment of Comparative Example 1. DETAILED DESCRIPTION

[0071] Various exemplary embodiments, features and aspects of the present invention will be described in detail below. The word "exemplary" used here means "used as an example, embodiment or illustrative". Any embodiment described here as "exemplary" is not necessarily interpreted as being superior or better than other embodiments.

[0072] In addition, in order to better illustrate the present invention, numerous specific details are provided in the following specific embodiments. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In other examples, methods, means, equipment and steps well known to those skilled in the art are not described in detail in order to highlight the subject matter of the present invention.

[0073] Unless otherwise stated, the units used in this specification are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0074] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0075] In this specification, the references to "some specific / preferred embodiments", "other specific / preferred embodiments", "embodiments", etc., mean that the specific elements (e.g., features, structures, properties and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not exist in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0076] In this specification, the numerical range expressed using "a numerical value A to a numerical value B" means a range including the endpoints numerical values ​​A and B.

[0077] In this specification, when "normal temperature" or "room temperature" is used, the temperature may be 23-25°C.

[0078] <Phase change hydrogel>

[0079] The invention provides a phase-change hydrogel, which comprises: a hydrogel and phase-change microcapsules dispersed in the hydrogel.

[0080] In some preferred embodiments, the content of the phase change microcapsules is 10-80% of the content of the hydrogel, preferably 35-70%.

[0081] In some specific embodiments, the content of phase change microcapsules is 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% of the content of the hydrogel.

[0082] In the present invention, the phase change microcapsules are evenly dispersed in the hydrogel to form a double network structure. Based on the good interaction between the phase change microcapsules and the double network hydrogel, the present invention obtains a long-lasting heat-insulating and stable phase change hydrogel. The phase change hydrogel of the present invention can provide a stable temperature during organ storage, reduce the impact of temperature fluctuations on the organ, and thus improve the success rate of transplantation. In addition, the phase change hydrogel of the present invention does not require external power supply, is simple and portable, and the phase change material can be recycled.

[0083] [Hydrogel]

[0084] The above-mentioned "hydrogel" is a substance in which a liquid with water as a dispersion medium undergoes a sol-gel phase transition, becomes hard and loses fluidity, and forms a porous structure. It can be formed by allowing a hydrophilic polymer to contain water and swell.

[0085] In some preferred embodiments, the hydrogel preferably comprises a first composition and a second composition.

[0086] The first composition preferably contains chitosan, an electrolyte, and at least one solvent selected from water and a buffer solution.

[0087] In some preferred embodiments, the first composition is obtained by the following method: dissolving chitosan and electrolyte in a buffer solution or water, thereby obtaining the first composition.

[0088] In some preferred embodiments, the content of chitosan is 0.9 to 10% by mass relative to the total amount of the first composition.

[0089] In some specific embodiments, the content of chitosan is 0.9 mass%, 1 mass%, 2 mass%, 3 mass%, 4 mass%, 5 mass%, 6 mass%, 7 mass%, 8 mass%, 9 mass% or 10 mass% relative to the total amount of the first composition.

[0090] Examples of chitosan include ethylene glycol chitosan, hydroxyethyl chitosan, and carboxymethyl chitosan.

[0091] In some preferred embodiments, the content of the electrolyte is 0.1 to 1% by mass, preferably 0.1 to 0.3% by mass, relative to the total amount of the first composition.

[0092] In some specific embodiments, the content of the electrolyte is 0.1 mass %, 0.2 mass %, 0.3 mass %, 0.4 mass %, 0.5 mass %, 0.6 mass %, 0.7 mass %, 0.8 mass %, 0.9 mass % or 1 mass % relative to the total amount of the first composition.

[0093] Examples of the electrolyte include calcium sulfate, calcium lactate, calcium hydrogen phosphate, and calcium chloride, and calcium chloride is preferred.

[0094] In some preferred embodiments, the content of the buffer solution or water is 20 to 99% by mass, preferably 60 to 99% by mass, relative to the total amount of the first composition.

[0095] In some specific embodiments, the content of the buffer solution or water is 20 mass%, 30 mass%, 40 mass%, 50 mass%, 60 mass%, 70 mass%, 80 mass%, 90 mass% or 99 mass% relative to the total amount of the first composition.

[0096] Examples of the buffer solution include sodium bicarbonate buffer, PBS buffer (phosphate buffer solution), and Tris-HCl buffer, and a sodium bicarbonate aqueous solution is preferred.

[0097] The second composition preferably contains alginate, an aldehyde-terminated polymer and water.

[0098] In some preferred embodiments, the second composition is obtained by the following method: dissolving alginate and an aldehyde-terminated polymer in water, thereby obtaining the second composition.

[0099] As alginate, various types of gel-forming but de-crosslinked alginates can be used, for example, sodium alginate, potassium alginate can be listed. Alginate can be commercially available from various sources, such as alginate manufactured by FMC BioPolymer (Philadelphia, PA).

[0100] In some preferred embodiments, the content of alginate is 0.9 to 10% by mass, preferably 0.9 to 4% by mass, relative to the total amount of the second composition.

[0101] In some preferred embodiments, the content of alginate is 0.9 mass%, 1 mass%, 2 mass%, 3 mass%, 4 mass%, 5 mass%, 6 mass%, 7 mass%, 8 mass%, 9 mass% or 10 mass% relative to the total amount of the second composition.

[0102] The aldehyde-terminated polymer includes aldehyde-terminated polyethylene glycol, aldehyde-terminated polyacrylic acid, aldehyde-terminated vinyl alcohol, dialdehyde-terminated polyethylene glycol diester, and the like, and aldehyde-terminated polyethylene glycol is preferred.

[0103] In some preferred embodiments, the content of the aldehyde-terminated polymer is 0.09 to 10% by mass, preferably 0.09 to 4% by mass, relative to the total amount of the second composition.

[0104] In some preferred embodiments, the content of the aldehyde-terminated polymer is 0.09 mass%, 0.1 mass%, 0.5 mass%, 1 mass%, 2 mass%, 3 mass%, 4 mass%, 5 mass%, 6 mass%, 7 mass%, 8 mass%, 9 mass% or 10 mass% relative to the total amount of the second composition.

[0105] In some preferred embodiments, the content of water is 20 to 99% by mass, preferably 60 to 99% by mass, relative to the total amount of the second composition.

[0106] In some preferred embodiments, the water content is 20 mass%, 30 mass%, 40 mass%, 50 mass%, 60 mass%, 70 mass%, 80 mass%, 90 mass% or 99 mass% relative to the total amount of the second composition.

[0107] In the present invention, the phase change microcapsules are evenly dispersed in the hydrogel to form a double network structure to ensure the uniform distribution of the microcapsules. The double network hydrogel has excellent ductility while ensuring good mechanical properties, and can achieve good coating of transplanted organs (such as kidneys) and ensure uniform temperature distribution.

[0108] [Phase change microcapsules]

[0109] In the present invention, the phase change microcapsules are preferably prepared as follows:

[0110] Step A: mixing a phase change material, a silane precursor, a polymerization monomer and an initiator;

[0111] Step B: dispersing the mixture obtained in the above step A in an aqueous solution containing an emulsifier for emulsification to obtain an emulsion;

[0112] Step C: subjecting the emulsion obtained in the above step B to polymerization reaction to obtain phase change microcapsules.

[0113] In the above step A, as the phase change material, for example, hydrocarbon compounds, fatty acid compounds, alcohol compounds, ester compounds, etc. can be listed. These can be used alone or in combination of two or more. Among these, from the viewpoint of better improving the phase change enthalpy value, the phase change material is preferably a hydrocarbon compound.

[0114] Examples of the hydrocarbon compound include aliphatic hydrocarbon compounds having 13 to 18 carbon atoms.

[0115] The aliphatic hydrocarbon compound having 13 to 18 carbon atoms may be a linear or branched aliphatic hydrocarbon compound, and examples thereof include, but are not limited to, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane.

[0116] As fatty acid compounds, saturated or unsaturated C6-C 12 Examples of fatty acids include, but are not limited to, caprylic acid, capric acid, and dodecanoic acid. These may be used alone or in combination of two or more.

[0117] As alcohol compound, preferably C3-C 16 Examples of fatty alcohols include, but are not limited to, glycerol, tetratetrol, dodecanol, tetradecanol, hexadecanol, and so-called oxo alcohols obtained by hydroformylating α-olefins and further reacting them, etc. These may be used alone or in combination of two or more.

[0118] As ester compounds, preferably C1-C 16 Examples of the alkyl ester include, but are not limited to, cetyl stearate, cellulose laurate, etc. These may be used alone or in combination of two or more.

[0119] In some preferred embodiments, the phase change temperature of the phase change material is 4 to 30° C. The phase change latent heat of the phase change energy storage material is preferably 110 to 270 kJ / kg, more preferably 130 to 250 kJ / kg.

[0120] As the silane precursor, preferably at least one of the group consisting of methyl orthosilicate, ethyl orthosilicate, tetraethyl orthosilicate, glycidyltrimethoxysilane, phenyltriethoxysilane, aminopropyltrimethoxysilane, aminopropyltriethoxysilane, phenyltrimethoxysilane, n-octyltriethoxysilane, octadecyltrimethoxysilane and propyltrimethoxysilane, tetra-n-butyl titanate, tetraisopropyl titanate, tetrabutyl stannate, tetrabutyl zirconate, triisopropyl aluminate, benzyl aluminate and boric acid.

[0121] Examples of the polymerizable monomer include styrene monomers, (meth)acrylate monomers, and diene monomers, etc. These may be used alone or in combination of two or more.

[0122] Specific examples of polymerizable monomers include, for example, styrene, divinylbenzene, ethylene glycol dimethacrylate, propylene glycol dimethacrylate, butylene glycol dimethacrylate, hexanediol dimethacrylate, methylstyrene, methyl methacrylate, ethyl methacrylate, butyl methacrylate, methyl acrylate, ethyl acrylate, butyl acrylate, tert-butyl acrylate, isooctyl acrylate, glycidyl methacrylate, 1,6-hexanediol diacrylate, polyethylene glycol dimethacrylate, butadiene, and at least one of isoprene. In some preferred embodiments, the polymerizable monomer is preferably at least one of styrene, divinylbenzene, and ethylene glycol dimethacrylate, so that the mechanical strength and toughness of the phase change microcapsules are excellent.

[0123] As the initiator, one or more of dibenzoyl peroxide, dodecyl peroxide, tert-butyl peroxyvalerate, diisopropyl peroxydicarbonate, diisopropyl peroxide, azobisisobutyronitrile and azobisisoheptylnitrile are preferred.

[0124] In some preferred embodiments, the content of the polymerized monomer is 1 to 50 parts by mass, preferably 10 to 40 parts by mass, relative to 100 parts by mass of the phase change material.

[0125] In some preferred embodiments, the mass ratio of the polymerized monomer to the phase change material is preferably 1:0.1 to 1:100, preferably 1:1 to 1:10.

[0126] In some preferred embodiments, the content of the silane precursor is 0.5 to 25 parts by mass, more preferably 2 to 15 parts by mass, relative to 100 parts by mass of the phase change material.

[0127] In some preferred embodiments, the mass ratio of the silane precursor to the phase change material is preferably 0.1:100 to 50:100, and more preferably 0.5:100 to 25:100.

[0128] In some preferred embodiments, the content of the initiator is 0.2 to 0.7 parts by mass relative to 100 parts by mass of the phase change material.

[0129] In some preferred embodiments, the mass ratio of the initiator to the phase change material is preferably 2:98 to 7:93, and more preferably 2:98 to 4:96.

[0130] In the above step B, the emulsifier is preferably one or more of styrene-maleic anhydride copolymer (1-10%) aqueous solution, cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), Tween 80, sodium dodecyl sulfate, polyoxyethylene ether sorbitan monooleate, and sorbitan monooleate.

[0131] In some preferred embodiments, the mass ratio of the emulsifier to the phase change material is preferably 1:99 to 10:90, and more preferably 1:99 to 5:95.

[0132] In the above step B, the volume ratio of the water phase to the oil phase is preferably 10:90 to 40:60, more preferably 20:80 to 30:70.

[0133] In the above step B, the emulsification is preferably high-speed shear emulsification or ultrasonic emulsification. When high-speed shear emulsification is used, the shear rate of high-speed shear emulsification is in the range of 1000 to 25000 rpm, and the shear time is in the range of 10s to 15min, preferably 30s to 5min. When ultrasonic emulsification is used, the ultrasonic frequency during ultrasonic emulsification is 1000 to 40000 Hz, and the ultrasonic emulsification time is 5 to 60min, preferably 10 to 60min.

[0134] In the above step C, the reaction temperature of the polymerization reaction is preferably 50 to 100° C., more preferably 65 to 75° C. The polymerization time is preferably 7 to 48 hours, more preferably 12 to 24 hours.

[0135] In the present invention, phase-change microcapsules encapsulated with silica and polymer are prepared based on interfacial sol, with polymerizable monomers, silica precursors, and paraffin as dispersed phases, and water or aqueous solution as continuous phases, and phase-change microcapsules are obtained through high-temperature polymerization and freeze-drying. The phase-change microcapsules in the present invention not only ensure that leakage does not occur, but also can be uniformly dispersed in the hydrogel prepared based on the interfacial sol-gel process to ensure uniform temperature distribution.

[0136] In some preferred embodiments, the average particle size of the phase change microcapsules is 2 to 3 μm.

[0137] In the present invention, the phase change microcapsule has a core-shell structure.

[0138] In some preferred embodiments, the core is the phase change material described above.

[0139] In the present invention, by introducing phase change microcapsules with a fixed melting point into the hydrogel, long-term thermal insulation and stable organ storage can be achieved, which can not only ensure that the temperature of the transplanted organ is maintained within the ideal range, but also reduce potential organ damage and improve the success rate of organ transplantation surgery.

[0140] <Method for preparing phase change hydrogel>

[0141] The present invention also provides a method for preparing a phase change hydrogel, which comprises:

[0142] Preparation of phase change microcapsules; and

[0143] Preparation process of phase change hydrogel,

[0144] The process of preparing the phase change hydrogel comprises:

[0145] The process of preparing the first solution is as follows: dissolving chitosan and electrolyte in water or a buffer solution to obtain the first solution;

[0146] The process of preparing the second liquid is as follows: dissolving alginate and aldehyde-terminated polymer in water, and adding the phase change microcapsules to obtain the second liquid;

[0147] The process of preparing the phase-change hydrogel is as follows: the first liquid and the second liquid are mixed and introduced into a mold for forming to obtain the phase-change hydrogel.

[0148] [Phase-change microcapsule preparation process]

[0149] The process of preparing phase change microcapsules includes:

[0150] Step A: mixing phase change material, silane precursor, polymer monomer and initiator;

[0151] Step B: dispersing the mixture obtained in the above step A in an aqueous solution containing an emulsifier for emulsification to obtain an emulsion;

[0152] Step C: subjecting the emulsion obtained in the above step B to polymerization reaction to obtain phase change microcapsules.

[0153] As the above-mentioned steps A to C, phase change materials, silane precursors, polymer monomers, initiators and emulsifiers, the same steps and substances as those described in the aforementioned "phase change hydrogel" can be listed.

[0154] [Phase-change hydrogel preparation process]

[0155] In the step of preparing the first liquid, chitosan and electrolyte may be the same as those used in the "hydrogel" in the aforementioned "phase change hydrogel", and the same methods may be used.

[0156] In the step of preparing the first liquid, the content of chitosan is 0.9 to 10% by mass, preferably 0.9 to 4% by mass, based on the total amount of the first liquid.

[0157] In some specific embodiments, the content of chitosan is 0.9 mass%, 1 mass%, 2 mass%, 3 mass%, 4 mass%, 5 mass%, 6 mass%, 7 mass%, 8 mass%, 9 mass% or 10 mass% relative to the total amount of the first liquid.

[0158] In the step of preparing the first liquid, the content of the electrolyte is 0.1 to 1% by mass, preferably 0.1 to 0.3% by mass, based on the total amount of the first liquid.

[0159] In some specific embodiments, the content of the electrolyte is 0.1 mass %, 0.2 mass %, 0.3 mass %, 0.4 mass %, 0.5 mass %, 0.6 mass %, 0.7 mass %, 0.8 mass %, 0.9 mass % or 1 mass % relative to the total amount of the first liquid.

[0160] In the step of preparing the first liquid, the content of water or the buffer solution is 20 to 99% by mass relative to the total amount of the first liquid.

[0161] In some specific embodiments, the content of the buffer solution or water is 20 mass%, 30 mass%, 40 mass%, 50 mass%, 60 mass%, 70 mass%, 80 mass%, 90 mass% or 99 mass% relative to the total amount of the first liquid.

[0162] Examples of the buffer solution include a sodium bicarbonate buffer solution, a PBS buffer solution (phosphate buffer solution), and a Tris-HCl buffer solution, and a sodium bicarbonate buffer solution is preferred.

[0163] In the step of preparing the second liquid, examples of the alginate and aldehyde-terminated polymer include the same ones as those used in the "hydrogel" in the aforementioned "phase change hydrogel", and the same methods can be used.

[0164] In some preferred embodiments, the content of alginate is 0.9 to 10% by mass, preferably 0.9 to 4% by mass, relative to the total amount of the second liquid.

[0165] In some preferred embodiments, the content of alginate is 0.9 mass%, 1 mass%, 2 mass%, 3 mass%, 4 mass%, 5 mass%, 6 mass%, 7 mass%, 8 mass%, 9 mass% or 10 mass% relative to the total amount of the second liquid.

[0166] In some preferred embodiments, the content of the aldehyde-terminated polymer is 0.09 to 10% by mass, preferably 0.09 to 4% by mass, relative to the total amount of the second liquid.

[0167] In some preferred embodiments, the content of the aldehyde-terminated polymer is 0.09 mass%, 0.1 mass%, 0.5 mass%, 1 mass%, 2 mass%, 3 mass%, 4 mass%, 5 mass%, 6 mass%, 7 mass%, 8 mass%, 9 mass% or 10 mass% relative to the total amount of the second liquid.

[0168] In some preferred embodiments, the content of water is 20 to 99% by mass, preferably 60 to 99% by mass, relative to the total amount of the second liquid.

[0169] In some preferred embodiments, the water content is 20 mass%, 30 mass%, 40 mass%, 50 mass%, 60 mass%, 70 mass%, 80 mass%, 90 mass% or 99 mass% relative to the total amount of the second liquid.

[0170] In some preferred embodiments, the content of the phase change microcapsules is 10-80% of the content of the hydrogel, preferably 35-70%.

[0171] In the above-mentioned process of preparing phase change hydrogel, the mixing operation can be carried out by ultrasonic, hand-shaking or vortex mixing dispersion. When using ultrasound, the ultrasonic power is preferably 200-400W, and the vortex mixing speed is preferably 200-800r / min.

[0172] The present invention introduces phase-change microcapsules to enable the organ to maintain a stable temperature during the entire storage process of the transplantation operation. The phase-change microcapsules absorb and release heat within a specific temperature range, achieving a constant temperature state for the organ, effectively solving the problem of temperature instability, and being suitable for transplantation operations that require a long waiting time.

[0173] The present invention achieves excellent temperature distribution by uniformly dispersing phase change microcapsules in the hydrogel to form a double network structure, which helps to avoid local temperature anomalies, improve the overall quality and survival rate of organs, and solve the uneven temperature problem in the prior art.

[0174] Example

[0175] The embodiments of the present invention will be described in detail below in conjunction with the examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. If no specific conditions are specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0176] Example 1

[0177] 0.1 g of ethylene glycol chitosan and 0.02 g of anhydrous calcium chloride were dissolved in 10.0 g of ultrapure water as the first liquid.

[0178] After dissolving 0.1 g of sodium alginate and 0.01 g of aldehyde-terminated polyethylene glycol in 10 g of ultrapure water, 10 g of phase change microcapsules (phase change temperature: 4° C.) were added and mixed evenly to prepare the second liquid.

[0179] The first liquid and the second liquid are quickly mixed, shaken evenly and then introduced into a mold to form a gel to obtain a phase change hydrogel.

[0180] The preparation of phase change microcapsules is as follows: including water phase preparation and oil phase preparation

[0181] Preparation of aqueous phase: 15 g of styrene-maleic anhydride copolymer aqueous solution was added to 75 mL of ultrapure water, and the pH of the mixed solution was adjusted to 2-3 with hydrochloric acid to prepare the aqueous phase.

[0182] Preparation of oil phase: 8 g of tetradecane, 1 g of aminopropyltriethoxysilane, 5 g of tetraethyl orthosilicate, 1 g of octadecyltrimethoxysilane, 6 g of divinylbenzene and 0.06 g of azobisisobutyronitrile were dissolved and mixed uniformly in a container to form the oil phase.

[0183] The oil phase is poured into the water phase and sheared for 3 to 5 minutes using a high-speed shearing machine. Then, the mixture is added to a flask and heated to 70°C for 12 to 24 hours. The reaction is stopped and the phase change microcapsules with a phase change temperature of 4 to 6°C are obtained after washing and drying. Figure 1 Scanning electron microscope (SEM) image of the prepared phase change microcapsules.

[0184] like Figure 2 As shown, cryo-scanning electron microscopy characterization revealed that the phase-change microcapsules were uniformly dispersed in the polymer network.

[0185] like Figure 3 As shown, the phase change hydrogel prepared in Example 1 was wrapped around the pig kidney, and a paperless recorder was used to monitor the real-time temperature change of the kidney. Figure 4 As shown in the figure, the results show that the kidney wrapped by the double network phase change hydrogel has an obvious phase change platform at around 4°C, and the insulation time reaches more than 30 minutes, achieving a good temperature control effect. As a control, Control is the temperature change curve of the pig kidney not covered with phase change hydrogel over time.

[0186] Comparative Example 1

[0187] Dissolve 0.1 g of ethylene glycol chitosan and 0.02 g of anhydrous calcium chloride in 10.0 g of ultrapure water as the first liquid.

[0188] 0.1 g of sodium alginate and 0.01 g of dialdehyde-terminated polyethylene glycol diester were dissolved in 10 g of ultrapure water as the second liquid.

[0189] The first liquid and the second liquid are quickly mixed, shaken evenly and then introduced into a mold to form a gel to obtain a hydrogel.

[0190] like Figure 5 As shown, cryo-scanning electron microscopy characterization showed that the hydrogel had a porous structure.

[0191] like Figure 6 As shown, the hydrogel prepared in Comparative Example 1 was wrapped around the pig kidney, and then a paperless recorder was used to monitor the real-time temperature changes of the kidney. Figure 7 As shown, the temperature of the pig kidney wrapped in the hydrogel double network hydrogel changes with time. The results show that the kidney has an obvious phase change platform near 4°C and has no temperature control effect.

[0192] It should be noted that, although the technical solution of the present invention is introduced with specific examples, those skilled in the art will appreciate that the present invention should not be limited thereto.

[0193] The embodiments of the present invention have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A phase change hydrogel, characterized in that: The phase-change hydrogel comprises: a hydrogel and phase-change microcapsules dispersed in the hydrogel.

2. The phase change hydrogel according to claim 1, characterized in that: The content of the phase-change microcapsules is 10-80% of the content of the hydrogel.

3. The phase change hydrogel according to claim 1 or 2, characterized in that: The hydrogel comprises a first composition and a second composition; The first composition comprises chitosan, an electrolyte, and a solvent selected from at least one of water and a buffer solution; The second composition comprises alginate, an aldehyde-terminated polymer and water.

4. The phase change hydrogel according to claim 3, characterized in that: In the first composition, the content of the chitosan is 0.9 to 10% by mass relative to the total amount of the first composition; In the first composition, the content of the electrolyte is 0.1 to 1 mass % relative to the total amount of the first composition; In the first composition, the content of the buffer solution or water is 20 to 99% by mass relative to the total amount of the first composition; In the second composition, the content of the alginate is 0.9 to 10% by mass relative to the total amount of the second composition; In the second composition, the content of the aldehyde-terminated polymer is 0.09 to 10% by mass relative to the total amount of the second composition; In the second composition, the content of water is 20 to 99% by mass relative to the total amount of the second composition; The chitosan comprises ethylene glycol chitosan, hydroxyethyl chitosan or carboxymethyl chitosan; The electrolyte comprises calcium sulfate, calcium lactate, calcium hydrogen phosphate or calcium chloride; The alginate comprises sodium alginate or potassium alginate; The aldehyde-terminated polymer comprises aldehyde-terminated polyethylene glycol, aldehyde-terminated polyacrylic acid, aldehyde-terminated vinyl alcohol or dialdehyde-terminated polyethylene glycol diester.

5. The phase change hydrogel according to claim 1 or 2, characterized in that: The average particle size of the phase change microcapsules is 2 to 3 μm; The phase-change microcapsule has a core-shell structure.

6. A method for preparing a phase change hydrogel according to any one of claims 1 to 5, characterized in that: The method comprises: Preparation of phase change microcapsules; and Preparation process of phase change hydrogel, Wherein, the process of preparing phase change hydrogel comprises: The process of preparing the first solution is as follows: dissolving chitosan and electrolyte in water or a buffer solution to obtain the first solution; The process of preparing the second liquid is as follows: dissolving alginate and aldehyde-terminated polymer in water, and adding the phase change microcapsules to obtain the second liquid; The process of preparing the phase-change hydrogel is as follows: the first liquid and the second liquid are mixed and introduced into a mold for forming to obtain the phase-change hydrogel.

7. The preparation method according to claim 6, characterized in that: The process of preparing phase change microcapsules comprises: Step A: mixing a phase change material, a silane precursor, a polymerization monomer and an initiator; Step B: dispersing the mixture obtained in the above step A in an aqueous solution containing an emulsifier for emulsification to obtain an emulsion; Step C: subjecting the emulsion obtained in the above step B to polymerization reaction to obtain phase change microcapsules.

8. The preparation method according to claim 7, characterized in that: The phase change material comprises paraffin; The silane precursor comprises two or more of tetraethyl orthosilicate, methyl orthosilicate, aminopropyltriethoxysilane, octadecyltrimethoxysilane and propyltrimethoxysilane methacrylate; The polymerizable monomer comprises at least one of styrene, divinylbenzene and ethylene glycol dimethacrylate; The initiator comprises at least one of dibenzoyl peroxide, dodecyl peroxide, tert-butyl peroxyvalerate, diisopropyl peroxydicarbonate, diisopropyl peroxide, azobisisobutyronitrile and azobisisoheptylonitrile; The emulsifier comprises at least one of styrene-maleic anhydride copolymer aqueous solution, hexadecyltrimethylammonium bromide, sodium lauryl sulfate, Tween 80, sodium lauryl sulfate, polyoxyethylene ether sorbitan monooleate, and sorbitan monooleate.

9. The preparation method according to claim 6 or 7, characterized in that: The process of preparing the first liquid satisfies at least one of the following: (a) in the first liquid, the content of the chitosan is 0.9 to 10% by mass relative to the total amount of the first liquid; (b) in the first liquid, the content of the electrolyte is 0.1 to 1 mass % relative to the total amount of the first liquid; (c) the content of water or buffer solution is 20 to 99% by mass relative to the total amount of the first liquid; (d) the buffer solution is a sodium bicarbonate buffer solution; (e) the chitosan comprises ethylene glycol chitosan, hydroxyethyl chitosan or carboxymethyl chitosan; (f) the electrolyte comprises calcium sulfate, calcium lactate, calcium hydrogen phosphate or calcium chloride; The process of preparing the second liquid satisfies at least one of the following: (g) in the second liquid, the content of the alginate is 0.9 to 10% by mass relative to the total amount of the second liquid; (h) in the second liquid, the content of the aldehyde-terminated polymer is 0.09 to 10% by mass relative to the total amount of the second liquid; (i) in the second liquid, the content of water is 20 to 99% by mass relative to the total amount of the second liquid; (j) the alginate comprises sodium alginate or potassium alginate; (m) The aldehyde-terminated polymer comprises aldehyde-terminated polyethylene glycol, aldehyde-terminated polyacrylic acid, aldehyde-terminated vinyl alcohol or dialdehyde-terminated polyethylene glycol diester.

10. Use of the phase change hydrogel according to any one of claims 1 to 5 in preparing thermal insulation materials for organ transplantation surgery.

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