Injectable gel composition, injectable gel as well as preparation method and application of injectable gel

Abstract

The invention provides an injectable gel composition, injectable gel as well as a preparation method and application of the injectable gel. The injectable gel composition comprises a degradable material and a non-degradable material; wherein the degradable material comprises one or a combination of more than two of silicate, gelatin, sodium alginate and glucan, and the non-degradable material comprises polyacrylamide or a derivative thereof; the mass ratio of the degradable material to the non-degradable material is (0.5-20): (0.5-20), and preferably, the mass ratio of the degradable material to the non-degradable material is (1-10): (1-10). The injectable gel prepared from the injectable gel composition has good injectability and embolism effect, catheter blockage is avoided, and convenience is provided for clinical use.

Description

Technical Field

[0001] The invention relates to an injectable gel composition, an injectable gel and a preparation method and application thereof, belonging to the field of medical materials. Background Art

[0002] At present, the clinical treatment of cardiovascular diseases such as aortic aneurysm, arteriovenous fistula and vascular malformation is mainly carried out through interventional embolization surgery, which is a type of liquid preparation that is injected into the blood vessels via a catheter to cause artificial embolism. Its working principle is to inject the embolic agent in a controlled manner into the supplying blood vessels of the lesion or organ, causing occlusion and interrupting the blood supply, so as to achieve the purpose of controlling bleeding and treating tumors and vascular diseases.

[0003] Among the liquid embolic agents currently on the market, the main embolic agent components are organic solvents dimethyl sulfoxide (DMSO) and ethylene-vinyl alcohol polymers. DMSO has certain toxic effects, reacts with protein hydrophobic groups, causes protein denaturation, has vascular toxicity and hepatotoxicity, and needs to be injected into the patient's body at an extremely slow speed clinically. If the injection speed is accelerated, it will cause vasospasm in the patient. In addition, ethylene-vinyl alcohol polymers are non-degradable in the body and exist in the patient's body for a long time, causing long-term inflammatory reactions in the patient's implant site. At the same time, liquid embolic agents also have problems such as catheter blockage during transportation, the need for special DMSO-tolerant catheters, etc., which also seriously aggravates the therapeutic effect of cardiovascular diseases and buries serious health risks. Therefore, there is an urgent need for injectable embolic agents that are good in embolic effect, safe, and easy to use.

[0004] Patent document 1 discloses an embolic agent and its preparation method and application. The embolic agent described in the patent document is generated by a cross-linking reaction of reactant raw materials, wherein the reactant raw materials include a dispersed phase and a mobile phase, wherein the dispersed phase includes poly(acrylamide-co-acrylonitrile), a cross-linking agent, a condensing agent and a solvent, wherein the cross-linking agent contains at least two carboxyl groups, and the mobile phase includes an emulsifier and mineral oil. The patent document provides a thermosensitive embolic agent, which mainly relies on body temperature to heat the material to a temperature higher than the critical solution temperature (UCST), thereby causing the material to expand to achieve the effect of embolization. However, the temperature of each individual patient and different parts of the body, even at different times and states, is different, and it is difficult to accurately regulate the temperature of the injection site and the degree of expansion of the material, so it is difficult to ensure the effect of its embolization. The patent document also does not provide experiments and corresponding effects of its use as an embolic agent in vivo. It is difficult for those skilled in the art to predict the effect of its use as an embolic product. In addition, cross-linking agents and condensing agents have certain cytotoxicity, and there are hidden dangers in the biocompatibility and safety of the product.

[0005] Patent document 2 discloses a vascular intervention drug-loaded gel embolic agent, which includes the following components: a mixed solution and a pH regulator, wherein the mixed solution includes a polyelectrolyte solution and a chemotherapy solution, wherein the polyelectrolyte solution includes an anion aqueous solution and a cation aqueous solution; wherein the mixed solution can be converted from a liquid state to a gel state when the pH value is 5 to 7. This patent utilizes the gelation principle of the polyelectrolyte gel system, and achieves embolism by regulating the pH of the mixed solution to convert it from a liquid state to a gel. However, in the blood vessels, the liquid state of the blood is a dynamic flow environment, which can easily cause the injected mixed solution and pH regulator to diffuse, reduce the solution concentration and pH adjustment effect, and thus affect the gelation and embolism effect. In addition, the patent document does not provide experimental data on its use as an embolic agent in vivo. It is difficult for those skilled in the art to predict the actual effect of its use as an embolic product.

[0006] References:

[0007] Patent document 1: CN108671262A

[0008] Patent document 2: CN115212343A Summary of the invention

[0009] Problem that the invention aims to solve

[0010] In view of the technical problems existing in the prior art, the present invention first provides an injectable gel composition and an injectable gel. The injectable gel composition of the present invention has simple ingredients, and the prepared injectable gel has good injectability and embolization effect, no tube blockage during delivery, and no additional special catheter is required for delivery. Moreover, the injectable gel does not require the use of organic solvents, and the material has good biocompatibility with the human body, providing a better choice for clinical use.

[0011] Furthermore, the present invention also provides a method for preparing an injectable gel, which is simple and easy to implement, and the raw materials are easy to obtain, and is suitable for mass production.

[0012] Solutions for solving problems

[0013] The present invention provides an injectable gel composition, which comprises a degradable material and a non-degradable material; wherein:

[0014] The degradable material includes one or a combination of two or more of silicate, gelatin, sodium alginate, and dextran, and the non-degradable material includes polyacrylamide or its derivatives;

[0015] The mass ratio of the degradable material to the non-degradable material is (0.5-20):(0.5-20), preferably (1-10):(1-10).

[0016] Furthermore, the silicate includes lithium magnesium silicate and / or sodium silicate; the polyacrylamide or its derivative includes polyacrylamide and / or polypropylacrylamide.

[0017] Further, the injectable gel composition also includes a first solvent and a second solvent;

[0018] The first solvent is used to make the degradable material form a first gel or a first solution; the second solvent is used to make the non-degradable material form a second gel; and,

[0019] The first solvent and the second solvent are the same or different; preferably, the first solvent and the second solvent are both water.

[0020] Furthermore, the mass ratio of the degradable material to the first solvent is (1-20):100, preferably (5-15):100; and / or the mass ratio of the non-degradable material to the second solvent is (1-50):100, preferably (5-20):100.

[0021] The present invention also provides an injectable gel kit, which comprises the injectable gel composition of the present invention.

[0022] The present invention also provides an injectable gel, which comprises the injectable gel composition of the present invention obtained by gelling; preferably, the injectable gel comprises a first gel or a first solution formed by a degradable material, a second gel formed by a non-degradable material, and a developer.

[0023] Furthermore, in the first gel or the first solution, the mass concentration of the degradable material is 1%-30%, preferably 5%-20%; and / or,

[0024] In the second gel, the mass concentration of the non-degradable material is 1%-50%, preferably 5%-20%.

[0025] Further, the developer is one or a combination of two or more of iodized oil, iodophenyl ester, sodium iodide, diatrizoate, iohexol, iodixanol, iohexol, iopromide, iobiprole, iotrolan, tantalum powder, barium sulfate, bismuth trioxide or zirconium oxide; and / or,

[0026] Based on the total mass of the injectable gel being 100%, the content of the developer is 1%-40%, preferably 8%-30%.

[0027] Furthermore, the injectable gel also contains drugs; preferably, the drugs include one or a combination of two or more of doxorubicin, epirubicin, apatinib, doxorubicin, mitomycin, and cisplatin.

[0028] The present invention also provides a method for preparing the injectable gel according to the present invention, which comprises the step of mixing the components of the injectable gel.

[0029] Furthermore, the preparation method comprises the following steps:

[0030] preparing a first gel or a first solution;

[0031] preparing a second gel;

[0032] mixing the first gel or the first solution with the second gel to obtain a mixed gel product;

[0033] A developer is added to the mixed gel product to obtain the injectable gel.

[0034] Further, the step of preparing the first gel or the first solution includes dissolving the degradable material in a first solvent to obtain the first gel or the first solution;

[0035] The step of preparing the second gel comprises dissolving the non-degradable material in a second solvent to obtain the second gel;

[0036] The first solvent and the second solvent are the same or different; preferably, the first solvent and the second solvent are both water.

[0037] The present invention also provides a use of the injectable gel according to the present invention in an embolic product; preferably, the embolic product comprises one or more of a vascular embolic product, an arteriovenous fistula product and an aneurysm embolic product.

[0038] Effects of the Invention

[0039] (1) The injectable gel prepared from the injectable gel composition of the present invention has good injectability and embolization effect, avoids clogging of the catheter, and provides convenience for clinical use.

[0040] (2) The injectable gel of the present invention comprises a first gel or a first solution formed by a degradable material and a second gel formed by a non-degradable material. As the degradable material in the first gel or the first solution degrades, it helps cells to proliferate in the colloid and then endothelialize, while the second gel provides a three-dimensional scaffold for cell growth, helps to accelerate endothelialization, and achieves faster embolization.

[0041] (3) The preparation method of the injectable gel of the present invention is simple and easy, the raw materials are easy to obtain, and it is suitable for mass production. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 A photograph showing the injectable gel of the present invention being injected to form a gel.

[0043] Figure 2 A photograph showing the injectable gel of the invention in a syringe.

[0044] Figure 3 A photograph of the abdominal aorta of a rat after injection of the injectable embolic agent of Example 1 is shown.

[0045] Figure 4 A photograph of the left kidney of a rabbit before injection of the injectable embolic agent of Example 1 is shown, and the color is bright red.

[0046] Figure 5 A photograph of the left kidney of a rabbit after injection of the injectable embolic agent of Example 1 is shown, and the color is dark red. DETAILED DESCRIPTION

[0047] 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.

[0048] 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.

[0049] 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.

[0050] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0051] 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.

[0052] 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.

[0053] In this specification, when "normal temperature" or "room temperature" is used, the temperature may be 10-40°C.

[0054] <First aspect>

[0055] The first aspect of the present invention provides an injectable gel composition, characterized in that it comprises a degradable material and a non-degradable material; wherein:

[0056] The degradable material includes one or a combination of two or more of silicate, gelatin, sodium alginate, and dextran, and the non-degradable material includes polyacrylamide or its derivatives;

[0057] The mass ratio of the degradable material to the non-degradable material is (0.5-20):(0.5-20), preferably (1-10):(1-10).

[0058] The injectable gel composition of the present invention has simple ingredients, and the prepared injectable gel has good injectability and embolization effect, no tube blockage during delivery, and no additional special catheter is required for delivery. Moreover, the injectable gel does not require the use of organic solvents, and the material has good biocompatibility with the human body, providing a better choice for clinical use.

[0059] Moreover, in the present invention, the mass ratio of the degradable material to the non-degradable material is (0.5-20):(0.5-20), preferably (1-10):(1-10), for example: (0.8-18):(0.8-18), (1-15):(1-15), (2-12):(2-12), (4-8):(4-8), etc.; when the mass ratio of the degradable material to the non-degradable material is (0.5-20):(0.5-20), preferably (1-10):(1-10), an injectable gel with good injectability and embolic effect can be obtained.

[0060] In some specific embodiments, in order to better form an injectable gel, the injectable gel composition also includes a first solvent and a second solvent; the first solvent is used to make the degradable material form a gel; the second solvent is used to make the non-degradable material form a gel; and the first solvent and the second solvent are the same or different; preferably, the first solvent and the second solvent are both water.

[0061] In the present invention, the degradable material and the non-degradable material can be separated. When used, the degradable material is prepared into a gel, and the non-degradable material is also prepared into a gel, and then the two are mixed. In the process of actual application, the degradable material and the non-degradable material can be stored separately, and then dissolved in the first solvent and the second solvent before or during use. The present invention does not limit the storage method of each component in the injectable gel composition. Personnel in the relevant technical field can select a specific storage method according to needs, all of which are within the scope of the present invention.

[0062] For ease of use, the degradable material can be stored in a pre-dissolved form in the first solvent, and the non-degradable material can be stored in a pre-dissolved form in the second solvent. For example, the degradable material can be dissolved in the first solvent and stored according to the concentration at the time of use, or the degradable material can be dissolved in a small amount of the first solvent and diluted with the first solvent before use; and / or the non-degradable material can be dissolved in the second solvent and stored according to the concentration at the time of use, or the non-degradable material can be dissolved in a small amount of the second solvent and diluted with the second solvent before use.

[0063] In some specific embodiments, the silicate includes lithium magnesium silicate and / or sodium silicate; the polyacrylamide or its derivative includes polyacrylamide and / or polypropylacrylamide.

[0064] In some specific embodiments, in order to finally form an injectable gel, the mass ratio of the degradable material to the first solvent is (1-20):100, preferably (5-15):100, for example: 2:100, 8:100, 10:100, 12:100, 18:100, etc.; and / or, the mass ratio of the non-degradable material to the second solvent is (1-50):100, preferably (5-20):100, for example: 8:100, 10:100, 12:100, 15:100, 18:100, 25:100, 30:100, 35:100, 40:100, 45:100, etc.

[0065] Furthermore, the present invention also provides an injectable gel kit, which includes the injectable gel composition of the present invention. In order to increase the shelf life of the injectable gel, the present invention can be in the form of an injectable gel kit, so that it can be prepared and used immediately.

[0066] Specifically, the injectable gel kit may include a degradable material and a non-degradable material. Preferably, the injectable gel kit may include a first solvent and a second solvent. The degradable material and the non-degradable material may be separated. When used, the degradable material is prepared into a first gel or a first solution, and the non-degradable material is prepared into a second gel, and then the two are mixed. In the actual application process, the degradable material and the non-degradable material can be stored separately, and then dissolved in the first solvent and the second solvent before or during use. The present invention does not limit the storage method of each component in the injectable gel composition. Personnel in the relevant technical field can select a specific storage method as needed, all within the scope of the present invention.

[0067] <Second Aspect>

[0068] The second aspect of the present invention provides an injectable gel, which comprises the injectable gel composition according to the first aspect after gelation; preferably, the injectable gel comprises a first gel or a first solution formed by a degradable material, a second gel formed by a non-degradable material, and a developer.

[0069] The injectable gel of the present invention comprises a first gel or a first solution formed by a degradable material and a second gel formed by a non-degradable material. As the degradable material in the first gel or the first solution degrades, it helps cells to proliferate in the colloid and then endothelialize, while the second gel provides a three-dimensional scaffold for cell growth, helps to accelerate endothelialization, and achieves faster embolization.

[0070] In order to obtain an injectable gel with excellent performance, in the first gel or the first solution of the present invention, the mass concentration of the degradable material is 1%-30%, preferably 5%-25%, for example: 2%, 8%, 10%, 12%, 18%, 20%, 22%, 25%, 28%, etc.

[0071] In the present invention, the degradable material includes one or a combination of two or more of silicate, gelatin, sodium alginate, and dextran, preferably silicate.

[0072] Specifically, the silicate includes lithium magnesium silicate and / or sodium silicate. The crystal structure unit of lithium magnesium silicate gel is a tiny flake with a thickness of nanometers. The surface of the small flake is covered with exchangeable cations, mainly Na + When the gel particles are mixed with water, the water and Na +The particles are adsorbed to the surface of the sheet and spread out along the sheet. At this time, the particles expand rapidly until the sheet separates. Since the sheet surface is negatively charged and the end surface is positively charged, the end surface of the separated sheet is attracted to the surface of another sheet, thus quickly forming a three-dimensional colloidal structure, increasing the viscosity of the system, and having high suspension, thickening, thixotropy, good compatibility, and chemical stability, it is an ideal hydrogel system.

[0073] In addition, sodium silicate also has a lot of Na + Similarly, when the gel particles are mixed with water, the water and Na + The contact and adsorption cause the sodium silicate to expand, and the sodium silicate particles expand rapidly until they separate to form a gel.

[0074] The non-degradable material of the present invention includes polyacrylamide or its derivatives. Polyacrylamide or its derivatives can be cross-linked polyacrylamide or its derivatives prepared by polymerization of acrylamide or its derivative monomers, 2,2'-dimethylbisacrylamide as a cross-linking agent, catalyzed by N,N,N',N'-tetramethylethylenediamine, and initiated by free radicals (photoinitiation, chemical initiation, etc.). The monomer can be acrylamide or propyl acrylamide.

[0075] In the present invention, in order to obtain an injectable gel with excellent performance, the mass concentration of polyacrylamide or its derivatives in the second gel is 1%-50%, preferably 5%-20%, for example: 2%, 8%, 10%, 12%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 45%, etc.

[0076] The injectable gel of the present invention may also contain a developer. The developer refers to a drug that turns the latent image generated by the photosensitive material after exposure into a visible image. From the perspective of chemical components, the developer can be divided into two categories: inorganic compounds and organic compounds. For inorganic compounds, it can be micron or nanometer-level barium sulfate, tantalum powder, bismuth trioxide, zirconium oxide, etc.; for organic compounds, it can be a combination of one or more of the developer including iodized oil, iodophenyl ester, sodium iodide, diatrizoate, iohexol, iodixanol, iopromide, iobiprole, and iotrolan. In the present invention, the introduction of tantalum powder can impart better developability. Therefore, in the present invention, the developer preferably includes tantalum powder. In some specific embodiments, in order to better achieve the development effect, based on the total mass of the injectable gel as 100%, the content of the developer is 1%-40%, preferably 8%-30%, for example: 5%, 10%, 15%, 18%, 20%, 25%, 30%, 35%, etc.

[0077] In the present invention, the injectable gel may also contain other ingredients feasible in the art, such as drugs, etc. Preferably, the drug includes one or a combination of two or more of adriamycin, epirubicin, apatinib, doxorubicin, mitomycin, and cisplatin.

[0078] <Third Aspect>

[0079] The third aspect of the present invention provides a method for preparing the injectable gel according to the second aspect of the present invention, which comprises the step of mixing the components of the injectable gel.

[0080] In the present invention, the first gel or the first solution and the second gel can be prepared separately, and then the first gel or the first solution and the second gel are mixed to form a mixed gel product; or the first gel or the first solution and the second gel can be directly mixed to form a mixed gel product.

[0081] In some specific embodiments, the preparation method may include the following steps:

[0082] preparing a first gel or a first solution;

[0083] preparing a second gel;

[0084] mixing the first gel or the first solution with the second gel to obtain a mixed gel product;

[0085] A developer is added to the mixed gel product to obtain an injectable gel.

[0086] Specifically, the step of preparing the first gel or the first solution includes mixing the degradable material with the first solvent to obtain the first gel or the first solution;

[0087] The step of preparing the second gel comprises mixing the non-degradable material with the second solvent to obtain the second gel;

[0088] The first solvent and the second solvent are the same or different; preferably, the first solvent and the second solvent are both water.

[0089] In some other specific embodiments, the preparation method may include the following steps:

[0090] Mixing the non-degradable material and the degradable material to obtain a mixed product;

[0091] The mixed product is subjected to gelation treatment to obtain a mixed gel product;

[0092] A developer is added to the mixed gel product to obtain an injectable gel.

[0093] Specifically, the gelation treatment includes dissolving the mixed product in a first solvent and / or a second solvent to obtain a mixed gel product;

[0094] The first solvent and the second solvent are the same or different; preferably, the first solvent and the second solvent are both water.

[0095] Furthermore, the present invention does not particularly limit the preparation conditions, and can be appropriately selected according to preparation requirements. Preferably, the preparation method of the present invention can be carried out at room temperature.

[0096] <Third Aspect>

[0097] The third aspect of the present invention provides a step of using the injectable gel according to the first aspect of the present invention to prepare an embolic product; preferably, the embolic product comprises one of a vascular embolic product, an arteriovenous fistula product and an aneurysm embolic product.

[0098] Example

[0099] 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.

[0100] Example 1

[0101] Take 1g of polyacrylamide, dissolve it in 10ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0102] Take 0.2g of lithium magnesium silicate and add it to 1ml of water. After the lithium magnesium silicate particles fully absorb water, lithium magnesium silicate gel is obtained.

[0103] The lithium magnesium silicate gel is added to the polyacrylamide gel to obtain a mixed gel product.

[0104] Take 1.2 g of tantalum powder, add it to the above mixed gel product, stir, and let it stand to obtain an injectable gel.

[0105] Example 2

[0106] Take 2.5 g of polypropylacrylamide, dissolve it in 8 ml of water, stir to dissolve the polypropylacrylamide, and obtain polyacrylamide gel.

[0107] Take 0.2 g of lithium magnesium silicate and add it to 4 ml of water. After the lithium magnesium silicate particles fully absorb water, lithium magnesium silicate gel is obtained.

[0108] The lithium magnesium silicate gel is added into the polypropylacrylamide gel to obtain a mixed gel product.

[0109] Take 3 g of iohexol and add it to the mixed gel product, stir it, and let it stand to obtain an injectable gel.

[0110] Example 3

[0111] Take 5 g of polyacrylamide, dissolve it in 10 ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0112] Take 0.5g of sodium silicate and add it to 4ml of water. After the sodium silicate particles fully absorb water, sodium silicate gel is obtained.

[0113] Sodium silicate gel is added to polyacrylamide gel to obtain a mixed gel product.

[0114] Take 2.0 g of zirconium oxide, add it to the above mixed gel product, stir, and let it stand to obtain an injectable gel.

[0115] Example 4

[0116] Take 3 g of polyacrylamide, dissolve it in 7 ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0117] Take 3g of lithium magnesium silicate and add it to 15ml of water. After the lithium magnesium silicate particles fully absorb water, lithium magnesium silicate gel is obtained.

[0118] The lithium magnesium silicate gel is added to the polyacrylamide gel to obtain a mixed gel product.

[0119] Take 5.5 g of iodophenyl ester and add it to the mixed gel product, stir and let it stand to obtain an injectable gel.

[0120] Example 5

[0121] Take 15 g of polyacrylamide, dissolve it in 75 ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0122] Take 5g of sodium silicate and add it to 50ml of water. After the sodium silicate particles fully absorb water, sodium silicate gel is obtained.

[0123] Sodium silicate gel is added to polyacrylamide gel to obtain a mixed gel product.

[0124] Take 20 g of diatrizoate and add it to the mixed gel product, stir and let it stand to obtain an injectable gel.

[0125] Example 6

[0126] Take 20g of polyacrylamide, dissolve it in 50ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0127] Take 4 g of lithium magnesium silicate and add it to 30 ml of water. After the lithium magnesium silicate particles fully absorb water, lithium magnesium silicate gel is obtained.

[0128] The lithium magnesium silicate gel is added to the polyacrylamide gel to obtain a mixed gel product.

[0129] Take 20 g of barium sulfate and add it to the above mixed gel product, stir and let it stand to obtain an injectable gel.

[0130] Example 7

[0131] Take 5 g of polypropylacrylamide, dissolve it in 50 ml of water, stir to dissolve the polypropylacrylamide, and obtain polypropylacrylamide gel.

[0132] Take 1.5g of gelatin, add it to 30ml of water, heat it at 50℃ to dissolve the gelatin, and obtain a gelatin solution.

[0133] Add the gelatin solution to the polypropylacrylamide gel and continue heating and stirring until the mixture is well mixed.

[0134] Take 2 g of tantalum powder, add it to the above solution, stir, let it stand, and cool it to room temperature to obtain an injectable gel.

[0135] Example 8

[0136] Take 1g of polyacrylamide, dissolve it in 10ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0137] Take 1g of sodium alginate, add it into 10ml of water, stir to dissolve the sodium alginate, and obtain a sodium alginate solution.

[0138] Add the sodium alginate solution into the polyacrylamide gel and continue stirring until the mixture is well mixed.

[0139] Take 1 g of iodophenyl ester and add it to the above mixed gel product, stir and let it stand to obtain an injectable gel.

[0140] Example 9

[0141] Take 1.5 g of polyacrylamide, dissolve it in 14 ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0142] Take 2 g of dextran, add it to 5 ml of water, stir to dissolve the dextran, and obtain a dextran solution.

[0143] Add the dextran solution to the polypropylacrylamide gel and continue stirring until the mixture is well mixed.

[0144] Take 1 g of iohexol and add it to the mixed gel product, stir it, and let it stand to obtain an injectable gel.

[0145] Comparative Example 1

[0146] Take 1g of polyacrylamide, dissolve it in 10ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0147] Comparative Example 2

[0148] The commercially available Onyx liquid embolic agent, which is composed of ethylene-polyvinyl alcohol copolymer and DMSO, was purchased and operated according to the instructions for use of the product.

[0149] Comparative Example 3

[0150] Take 0.01 g of polyacrylamide, dissolve it in 10 ml of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0151] Take 2.5g of lithium magnesium silicate and add it to 5ml of water. After the lithium magnesium silicate particles fully absorb water, lithium magnesium silicate gel is obtained.

[0152] The lithium magnesium silicate gel is added to the polyacrylamide gel to obtain a mixed gel product.

[0153] 0.2 g of zirconium oxide is added to the above mixed gel product to prepare the mixture.

[0154] Comparative Example 4

[0155] Take 10 g of polyacrylamide, add it to 15 mL of water, stir to dissolve the polyacrylamide, and obtain polyacrylamide gel.

[0156] Take 0.02 g of lithium magnesium silicate and add it to 2 mL of water. After the lithium magnesium silicate particles fully absorb water, lithium magnesium silicate gel is obtained.

[0157] The lithium magnesium silicate gel is added to the polyacrylamide gel to obtain a mixed gel product.

[0158] Take 35g of sodium iodide and add it to the above mixed gel product to prepare it.

[0159] Performance Testing

[0160] 1. Injectability evaluation

[0161] Take the samples of Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, Example 7, Example 8, Example 9 and Comparative Example 1, Comparative Example 2, Comparative Example 3 and Comparative Example 4, load them into a 3mL syringe, screw on a 3F catheter, and immerse the end of the catheter in water. Then load the syringe on a tensile testing machine, press the syringe push rod downward at a speed of 2mL / min, and use a 100N pressure sensor to detect the pressure. The results are shown in Table 1 below.

[0162] Table 1

[0163] sample Pressure(N) Example 1 35 Example 2 44 Example 3 58 Example 4 48 Example 5 30 Example 6 50 Example 7 44 Example 8 40 Example 9 37 Comparative Example 1 / Comparative Example 2 / Comparative Example 3 19 Comparative Example 4 /

[0164] As can be seen from Table 1, Examples 1-6 can all obtain injectable gels. In Comparative Examples 1, 2, and 4, tube blockage occurred during the injection process, and the pressure value exceeded the maximum range of the sensor, and detection could not be continued. The gel injected in Comparative Example 3 was very thin, not in strips, and easily dispersed in water, and could not be used as an embolism.

[0165] 2. Evaluation of in vitro thrombotic effect

[0166] Blood preparation: Take 5 mL of rabbit blood containing sodium citrate and add it into a sterile centrifuge tube. Add calcium chloride solution to activate the blood.

[0167] The samples prepared in Example 1, Example 3, Example 5 and Comparative Example 1 were taken respectively and added to a 24-well plate, and Example 1 group, Example 3 group, Example 5 group, Comparative Example 1 group and blank group were set respectively. 0.2 mL of gel was added to each well of Example 1 group, Example 3 group, Example 5 group and Comparative Example 1 group, and 3 wells were added to each sample, and no sample was added to the blank group. The blood prepared above was added to Example 1 group, Example 3 group, Example 5 group, Comparative Example 1 group and blank group respectively with a pipette, and 400 uL of blood was added to each well, and the blood complete coagulation time was recorded. The results are shown in Table 2.

[0168] Table 2

[0169] sample Blood complete coagulation time (min) Example 1 4min Example 3 3min Example 5 5min Comparative Example 1 8min Blank Group 11min

[0170] It can be seen from Table 2 that the blood complete coagulation time of the injectable gel of the present invention is lower than that of the comparative example 1 and the blank group. Therefore, the injectable gel of the present invention has excellent coagulation performance, can quickly form thrombus, and play a role in hemostasis.

[0171] 3. Animal embolism experiment

[0172] The samples of Example 1, Example 2 and Example 3 were respectively taken to carry out the following animal experiments to verify the embolization effect of the material of the present invention.

[0173] Nine rats were anesthetized and placed on an experimental operating table. The abdominal aorta of the rats was exposed and the above samples were injected into the abdominal aorta of the rats respectively. Three animals were tested for each sample. After injection, the injection site was observed for blood leakage and movement of the embolic material.

[0174] Nine rabbits were anesthetized and placed on the experimental operating table. The left renal artery of the rats was exposed. The kidney color was observed and recorded before injection. The above samples were injected into the left renal artery. Three animals were tested for each sample. After injection, the injection site was observed for blood leakage and kidney color changes. The results are shown in Table 3 and Figure 3-5 shown.

[0175] Table 3

[0176]

[0177] From Table 3 and Figure 3-5 It can be seen that the sample prepared by the present invention can effectively embolize blood vessels.

[0178] 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.

[0179] 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. An injectable gel composition, characterized in that: Including degradable materials and non-degradable materials; among which, The degradable material includes one or a combination of two or more of silicate, gelatin, sodium alginate, and dextran, and the non-degradable material includes polyacrylamide or its derivatives; The mass ratio of the degradable material to the non-degradable material is (0.5-20):(0.5-20), preferably (1-10):(1-10).

2. The injectable gel composition according to claim 1, characterized in that: The silicate includes lithium magnesium silicate and / or sodium silicate; the polyacrylamide or its derivative includes polyacrylamide and / or polypropylacrylamide.

3. The injectable gel composition according to claim 1 or 2, characterized in that: The injectable gel composition also includes a first solvent and a second solvent; The first solvent is used to make the degradable material form a first gel or a first solution; the second solvent is used to make the non-degradable material form a second gel; and, The first solvent and the second solvent are the same or different; preferably, the first solvent and the second solvent are both water.

4. The injectable gel composition according to claim 3, characterized in that: The mass ratio of the degradable material to the first solvent is (1-20):100, preferably (5-15):100; and / or the mass ratio of the non-degradable material to the second solvent is (1-50):100, preferably (5-20):

100.

5. An injectable gel kit, characterized in that: The invention comprises the injectable gel composition according to any one of claims 1 to 4.

6. An injectable gel, characterized in that The injectable gel composition according to any one of claims 1 to 4 is obtained by gelling; preferably, the injectable gel comprises a first gel or a first solution formed by a degradable material, a second gel formed by a non-degradable material, and a developer.

7. The injectable gel according to claim 6, characterized in that In the first gel or the first solution, the mass concentration of the degradable material is 1%-30%, preferably 5%-20%; and / or, In the second gel, the mass concentration of the non-degradable material is 1%-50%, preferably 5%-20%.

8. The injectable gel according to claim 6 or 7, characterized in that The developer is one or a combination of two or more of iodized oil, iodophenyl ester, sodium iodide, diatrizoate, iohexol, iodixanol, iohexol, iopromide, iobiprole, iotrolan, tantalum powder, barium sulfate, bismuth trioxide or zirconium oxide; and / or, Based on the total mass of the injectable gel being 100%, the content of the developer is 1%-40%, preferably 8%-30%.

9. The injectable gel according to any one of claims 6 to 8, characterized in that The injectable gel further comprises a drug; preferably, the drug comprises one or a combination of two or more of doxorubicin, epirubicin, apatinib, doxorubicin, mitomycin, and cisplatin.

10. A method for preparing an injectable gel according to any one of claims 6 to 9, characterized in that: The step of mixing the components of the injectable gel is included.

11. The preparation method according to claim 10, characterized in that: The preparation method comprises the following steps: preparing a first gel or a first solution; preparing a second gel; mixing the first gel or the first solution with the second gel to obtain a mixed gel product; A developer is added to the mixed gel product to obtain the injectable gel.

12. The preparation method according to claim 11, characterized in that: The step of preparing the first gel or the first solution comprises dissolving the degradable material in a first solvent to obtain the first gel or the first solution; The step of preparing the second gel comprises dissolving the non-degradable material in a second solvent to obtain the second gel; The first solvent and the second solvent are the same or different; preferably, the first solvent and the second solvent are both water.

13. Use of the injectable gel according to any one of claims 6 to 9 for embolic products; preferably, the embolic products include one or more of vascular embolic products, arteriovenous fistula products and aneurysm embolic products.

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