Temperature-sensitive polymer with good fluidity, embolic material and preparation method thereof

Abstract

This invention relates to the field of interventional medicine, specifically a highly fluid temperature-sensitive polymer, an embolic material, and a method for preparing the same. The temperature-sensitive polymer is a copolymerized polymer using N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) as monomers in a weight percentage range of 75:25 to 50:50. The temperature-sensitive polymer has a degree of polymerization of 3.2 to 8.4 × 10⁻⁶. 4 Temperature-sensitive polymer-1 was used to prepare an embolic material with good flow properties using a solution of temperature-sensitive polymer and a developer. The prepared embolic material has the advantages of good flowability at room temperature, non-sticking to the tube, non-clogging, easy injection, and good operability.

Description

Technical Field

[0001] This invention relates to the field of interventional medicine, specifically to a temperature-sensitive polymer with good flowability, an embolic material, and a method for preparing the same. Background Technology

[0002] Interventional therapy is one of the fastest-growing disciplines, and embolization therapy is an important component of interventional therapy. Embolization therapy involves the controlled injection of a thrombus into the blood vessels supplying the diseased organ via an arterial or venous catheter, causing occlusion and interrupting blood supply. The aim is to control bleeding, treat tumors and vascular lesions, and eliminate the function of the affected organ.

[0003] The choice of embolization material determines the success of embolization therapy. Embolization materials should possess the following characteristics: 1. Good fluidity, easy to inject via catheter, without sticking to or blocking the catheter; 2. Reasonable in vitro conversion time, easy diffusion and filling into the tumor's terminal vessels, forming a vascular cast; 3. Reasonable embolization strength, resisting blood flow erosion, maintaining long-term vascular embolization effects; 4. Good visibility, i.e., X-ray shielding capability, guiding the embolic agent to the correct target site. Chinese patent CN 1233676C discloses a temperature-sensitive polymer, a temperature-sensitive liquid embolization material, and its preparation method. This liquid embolization material has certain fluidity and temperature sensitivity, but its viscosity is too low, resulting in poor diffusion. Clinically, it is prone to being washed away by blood flow and dispersing. Furthermore, its in vitro conversion time is too short, making it difficult to diffuse and fill into the tumor's terminal vessels, and clinicians do not have sufficient time for surgical procedures. Summary of the Invention

[0004] To address the aforementioned technical problems, a first aspect of the present invention provides a temperature-sensitive polymer with good flowability. This temperature-sensitive polymer is a copolymer formed by copolymerizing N-isopropylacrylamide (represented by NIP) and N-n-propylacrylamide (represented by NNP) in a weight percentage range of 75:25 to 50:50. The temperature-sensitive polymer comprises polymers with a degree of polymerization of 3.2 × 10⁻⁶. 4 ~8.4×10 4 Temperature-sensitive polymer-1.

[0005] As a preferred embodiment of the present invention, the temperature-sensitive polymer further includes a degree of polymerization of 3.5 × 10⁻⁶. 6 ~7×10 6 Temperature-sensitive polymer-2.

[0006] As a preferred embodiment of the present invention, the weight ratio of the temperature-sensitive polymer-1 to the temperature-sensitive polymer-2 is (1-4):1.

[0007] As a preferred embodiment of the present invention, the weight ratio of the temperature-sensitive polymer-1 to the temperature-sensitive polymer-2 is (1.8-2.6):1.

[0008] As a preferred embodiment of the present invention, the phase transition temperature of the temperature-sensitive polymer is 28-36℃.

[0009] A second aspect of the invention provides an embolization material comprising a solution of any of the above-described temperature-sensitive polymers and a developer.

[0010] As a preferred embodiment of the present invention, the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent.

[0011] As a preferred embodiment of the present invention, the solvent is physiological saline and / or water for injection.

[0012] As a preferred embodiment of the present invention, the developer is a water-soluble developer.

[0013] A third aspect of the present invention provides a method for preparing an embolic material, comprising the following preparation steps:

[0014] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer;

[0015] S2: The solution of the temperature-sensitive polymer is stirred and mixed evenly with the developer to obtain the embolus.

[0016] Beneficial effects:

[0017] 1. Most current liquid embolization materials contain organic solvents, while the solvent used in the embolization material of this invention is water for injection, which is non-toxic, non-irritating, and has good biocompatibility.

[0018] 2. The polymer of the present invention has temperature-sensitive properties, and the embolization material of the present invention has good dispersibility. It is not easily washed away by blood flow and dispersed during clinical work, thus having good safety.

[0019] 3. The embolization material of the present invention has good fluidity at room temperature, does not stick to the tube or block the tube during use, is easy to inject, and has good operability;

[0020] 4. The in vitro conversion time of the embolic material of the present invention is within a suitable range, exhibiting good safety and operability;

[0021] 5. The embolization material of the present invention contains a contrast agent that plays a role in contrast during clinical procedures. Detailed Implementation

[0022] The invention will be more readily understood by referring to the following detailed description of preferred embodiments and included examples. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of conflict, the definitions in this specification shall prevail.

[0023] As used herein, the terms “prepared from” and “comprising” are synonymous. The terms “comprising,” “including,” “having,” “containing,” or any other variations thereof, as used herein, are intended to cover non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that includes the listed elements is not necessarily limited to those elements, but may include other elements not expressly listed or elements inherent to such composition, step, method, article, or apparatus.

[0024] The conjunction "composed of..." excludes any unspecified elements, steps, or components. If used in a claim, this phrase makes the claim closed, excluding materials other than those described, except for associated conventional impurities. When the phrase "composed of..." appears in a clause of the body of a claim rather than immediately following it, it limits only the elements described in that clause; other elements are not excluded from the claim as a whole.

[0025] When a quantity, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pair of any upper or preferred value with any lower or preferred value, regardless of whether the range is disclosed individually. For example, when the range “1 to 5” is disclosed, the described range should be interpreted as including the ranges “1 to 4”, “1 to 3”, “1 to 2”, “1 to 2 and 4 to 5”, “1 to 3 and 5”, etc. When numerical ranges are described herein, unless otherwise stated, the range is intended to include its endpoints and all integers and fractions within that range.

[0026] The singular form includes the plural objects of discussion unless the context clearly indicates otherwise. "Optional" or "any one" means that the matter or event described thereafter may or may not occur, and the description includes both the possibility that the event occurs and the possibility that the event does not occur.

[0027] Approximate terms used in the specification and claims to modify quantities indicate that the invention is not limited to that specific quantity, but also includes acceptable modifications close to that quantity that do not alter the relevant essential function. Correspondingly, the use of "about," "approximately," etc., to modify a numerical value means that the invention is not limited to that precise value. In some instances, approximate terms may correspond to the precision of the instrument used to measure the value. In this application's specification and claims, scope definitions can be combined and / or interchanged, unless otherwise stated, these scopes include all subscopes contained therein.

[0028] Furthermore, the indefinite articles “a” and “an” preceding the elements or components of this invention do not impose any limitation on the quantity requirement (i.e., the number of times) of the elements or components. Therefore, “an” or “a” should be interpreted as including one or at least one, and the singular form of an element or component also includes the plural form, unless the quantity clearly refers to the singular form.

[0029] To address the aforementioned technical problems, a first aspect of the present invention provides a temperature-sensitive polymer with good flowability. This temperature-sensitive polymer is a copolymer formed by copolymerizing N-isopropylacrylamide (represented by NIP) and N-n-propylacrylamide (represented by NNP) in a weight percentage range of 75:25 to 50:50. The temperature-sensitive polymer comprises polymers with a degree of polymerization of 3.2 × 10⁻⁶. 4 ~8.4×10 4 Temperature-sensitive polymer-1.

[0030] In a preferred embodiment, the temperature-sensitive polymer is a copolymerized polymer of N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage range of 70:30; the temperature-sensitive polymer comprises polymers with a degree of polymerization of 3.2 × 10⁻⁶. 4 ~8.4×10 4 Temperature-sensitive polymer-1.

[0031] In a preferred embodiment, the degree of polymerization of the temperature-sensitive polymer-1 is 5 × 10⁻⁶. 4 ~7.8×10 4 More preferably, the degree of polymerization of the temperature-sensitive polymer-1 is 6.3 × 10⁻⁶. 4 .

[0032] The applicant found that when the weight percentage of monomers NIP to NNP was between 75:25 and 50:50, a degree of polymerization of 3.2 × 10⁻⁶ was optimal. 4 ~8.4×10 4 The temperature-sensitive polymer-1 gives the embolic material good flowability, possibly due to its degree of polymerization of 3.2 × 10⁻⁶.4 ~8.4×10 4 The embolic material prepared from the temperature-sensitive polymer-1 has a low density of three-dimensional network structure, which increases the mobile phase.

[0033] In one embodiment, the temperature-sensitive polymer further includes a degree of polymerization of 3.5 × 10⁻⁶. 6 ~7×10 6 The temperature-sensitive polymer-2; more preferably, the degree of polymerization of the temperature-sensitive polymer-2 is 4.2 × 10⁻⁶. 6 ~5.6×10 6 More preferably, the degree of polymerization of the temperature-sensitive polymer-2 is 4.8 × 10⁻⁶. 6 .

[0034] In one embodiment, the weight ratio of the temperature-sensitive polymer-1 to the temperature-sensitive polymer-2 is (1-4):1.

[0035] In a preferred embodiment, the weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is (1.8-2.6):1; more preferably, the weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 2.3:1.

[0036] The applicant discovered that when a certain amount of polymer with a degree of polymerization of 3.5 × 10⁻⁶ was used... 6 ~7×10 6 The synergistic effect of temperature-sensitive polymer-2 and temperature-sensitive polymer-1 not only does not reduce the fluidity of the embolic material, but also, to a certain extent, keeps the in vitro conversion time of the embolic material within a suitable range, further enhancing the operability of the embolic material in clinical practice. This may be because the two temperature-sensitive polymers with different degrees of polymerization have a certain synergistic effect.

[0037] In one embodiment, a temperature-sensitive polymer with a phase transition temperature varying between 28-36°C is obtained by adjusting the ratio of N-isopropylacrylamide to N-n-propylacrylamide.

[0038] In one embodiment, the method for preparing the temperature-sensitive polymer includes the following steps:

[0039] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0040] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0041] (3) Preparation of temperature-sensitive polymer: Weigh out the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0042] In one embodiment, the initiator is 14% of the weight of N-isopropylacrylamide.

[0043] In one embodiment, the initiator is sodium sulfite and potassium persulfate, wherein the weight ratio of sodium sulfite to potassium persulfate is 1:3.

[0044] In one embodiment, temperature-sensitive polymers with different degrees of polymerization are obtained by controlling the reaction time and reaction temperature in reaction step (3), wherein the temperature of the polymerization reaction in step (3) is controlled to be 5-20°C.

[0045] In one embodiment, the molar ratio of isopropylamine to acryloyl chloride is 2:1.

[0046] In one embodiment, the molar ratio of n-propylamine to acryloyl chloride is 2:1.

[0047] In one embodiment, the volume ratio of ethyl acetate to n-propylamine is 1:1.

[0048] In one embodiment, the volume ratio of n-propylamine to toluene is 1:1.

[0049] A second aspect of the invention provides an embolization material comprising a solution of any of the temperature-sensitive polymers described above and a developer.

[0050] In one embodiment, the solution of the temperature-sensitive polymer comprises the temperature-sensitive polymer and a solvent.

[0051] In one embodiment, the solvent is physiological saline and / or water for injection.

[0052] In a preferred embodiment, the solvent is water for injection.

[0053] In a preferred embodiment, the solution of the temperature-sensitive polymer further includes 0.05 mol / L of medical-grade dilute hydrochloric acid.

[0054] In one embodiment, the weight of the medical dilute hydrochloric acid is 0.2-0.6% of the weight of the temperature-sensitive polymer solution; more preferably, the weight of the medical dilute hydrochloric acid is 0.3-0.5% of the weight of the temperature-sensitive polymer solution; and even more preferably, the weight of the medical dilute hydrochloric acid is 0.4% of the weight of the temperature-sensitive polymer solution.

[0055] The applicant unexpectedly discovered that adding a certain amount of medical-grade dilute hydrochloric acid to the system of this invention can improve the fluidity of the embolic material. This is likely because medical-grade dilute hydrochloric acid can ionize to release a certain amount of H₂. + H + The interaction with temperature-sensitive polymers increases the surface smoothness and reduces the angle of repose of the solidified material upon solidification, thereby increasing the fluidity of the embolic material. More importantly, this invention uses a polymerization degree of 3.2 × 10⁻⁶. 4 ~8.4×10 4 The temperature-sensitive polymer-1 reduces the viscosity of the system and worsens the divergence of the embolic material. The trace amounts of H in the system... + The presence of [something] improves the divergence of the embolization material.

[0056] In one embodiment, the developer is a water-soluble developer.

[0057] Examples of water-soluble developing agents include iohexol, iodized oil, iodixanol, meglumine diatrizoate, and iotram; more preferably, the water-soluble developing agent is iohexol (iodine content of 46.4%).

[0058] A third aspect of the present invention provides a method for preparing an embolic material, comprising the following preparation steps:

[0059] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer;

[0060] S2: The solution of temperature-sensitive polymer is stirred and mixed evenly with developer to obtain embolization material.

[0061] In one embodiment, information on some of the chemical raw materials used is shown in Table 1:

[0062] Table 1

[0063]

[0064]

[0065] Several specific embodiments of the present invention are given below, but the present invention is not limited to these embodiments.

[0066] In addition, unless otherwise specified, all raw materials used in this invention are commercially available.

[0067] Example

[0068] Example 1

[0069] Preparation of temperature-sensitive polymers:

[0070] A temperature-sensitive polymer is a copolymer of N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage ratio of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 7.8 × 10⁻⁶. 4 The temperature-sensitive polymer further includes temperature-sensitive polymer-2; the degree of polymerization of temperature-sensitive polymer-2 is 4.2 × 10⁻⁶. 6 The weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 1.8:1.

[0071] The method for preparing the temperature-sensitive polymer includes the following steps:

[0072] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0073] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0074] (3) Preparation of temperature-sensitive polymer: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0075] (4) Preparation of temperature-sensitive polymer-2: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0076] Among them, the reaction temperature and time in steps (3) and (4) are different, and the degree of polymerization of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method;

[0077] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, with a weight ratio of sodium sulfite to potassium persulfate of 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0078] Preparation of embolic materials:

[0079] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent; the solvent is water for injection; the solution of the temperature-sensitive polymer further comprises 0.05 mol / L medical-grade dilute hydrochloric acid; the weight of the medical-grade dilute hydrochloric acid is 0.3% of the weight of the solution of the temperature-sensitive polymer; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0080] The method for preparing the embolic material includes the following preparation steps:

[0081] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0082] Example 2

[0083] Preparation of temperature-sensitive polymers:

[0084] A temperature-sensitive polymer is a copolymer formed by copolymerizing N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage ratio of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 5 × 10⁻⁶. 4 The temperature-sensitive polymer further includes temperature-sensitive polymer-2; the degree of polymerization of temperature-sensitive polymer-2 is 5.6 × 10⁻⁶. 6The weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 2.6:1.

[0085] The method for preparing the temperature-sensitive polymer includes the following steps:

[0086] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0087] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0088] (3) Preparation of temperature-sensitive polymer-1: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0089] (4) Preparation of temperature-sensitive polymer-2: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0090] Among them, the reaction temperature and time in steps (3) and (4) are different, and the degree of polymerization of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method;

[0091] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, with a weight ratio of sodium sulfite to potassium persulfate of 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0092] Preparation of embolic materials:

[0093] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent. The solvent is water for injection; the solution of the temperature-sensitive polymer further comprises 0.05 mol / L medical-grade dilute hydrochloric acid; the weight of the medical-grade dilute hydrochloric acid is 0.3-0.5% of the weight of the temperature-sensitive polymer solution; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0094] The method for preparing the embolic material includes the following preparation steps:

[0095] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0096] Example 3

[0097] Preparation of temperature-sensitive polymers:

[0098] A temperature-sensitive polymer is a copolymer of N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage ratio of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 6.3 × 10⁻⁶. 4 The temperature-sensitive polymer further includes temperature-sensitive polymer-2; the degree of polymerization of temperature-sensitive polymer-2 is 4.8 × 10⁻⁶. 6 The weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 2.3:1.

[0099] The method for preparing the temperature-sensitive polymer includes the following steps:

[0100] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0101] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0102] (3) Preparation of temperature-sensitive polymer: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0103] (4) Preparation of temperature-sensitive polymer-2: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0104] Among them, the reaction temperature and time in steps (3) and (4) are different, and the degree of polymerization of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method;

[0105] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, wherein the weight ratio of sodium sulfite to potassium persulfate is 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0106] Preparation of embolic materials:

[0107] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent. The solvent is water for injection; the solution of the temperature-sensitive polymer further comprises 0.05 mol / L medical-grade dilute hydrochloric acid; the weight of the medical-grade dilute hydrochloric acid is 0.4% of the weight of the solution of the temperature-sensitive polymer; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0108] The method for preparing the embolic material includes the following preparation steps:

[0109] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0110] Example 4

[0111] Preparation of temperature-sensitive polymers:

[0112] A temperature-sensitive polymer is a copolymer formed by copolymerizing N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage ratio of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 1×10⁻⁶. 4 The temperature-sensitive polymer further includes temperature-sensitive polymer-2; the degree of polymerization of temperature-sensitive polymer-2 is 4.8 × 10⁻⁶. 6 The weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 2.3:1.

[0113] The method for preparing the temperature-sensitive polymer includes the following steps:

[0114] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0115] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0116] (3) Preparation of temperature-sensitive polymer: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0117] (4) Preparation of temperature-sensitive polymer-2: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0118] Among them, the reaction temperature and time in steps (3) and (4) are different, and the degree of polymerization of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method;

[0119] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, with a weight ratio of sodium sulfite to potassium persulfate of 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0120] Preparation of embolic materials:

[0121] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent; the solvent is water for injection; the solution of the temperature-sensitive polymer further comprises 0.05 mol / L medical-grade dilute hydrochloric acid; the weight of the medical-grade dilute hydrochloric acid is 0.4% of the weight of the solution of the temperature-sensitive polymer; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0122] The method for preparing the embolic material includes the following preparation steps:

[0123] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0124] Example 5

[0125] Preparation of temperature-sensitive polymers:

[0126] A temperature-sensitive polymer is a copolymer of N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage ratio of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 6.3 × 10⁻⁶. 4 ;

[0127] The method for preparing the temperature-sensitive polymer includes the following steps:

[0128] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0129] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0130] (3) Preparation of temperature-sensitive polymer: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0131] The degree of polymerization of temperature-sensitive polymer-1 was determined by the Ubbelohde viscometer method;

[0132] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, with a weight ratio of sodium sulfite to potassium persulfate of 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0133] Preparation of embolic materials:

[0134] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent; the solvent is water for injection; the solution of the temperature-sensitive polymer further comprises 0.05 mol / L medical-grade dilute hydrochloric acid; the weight of the medical-grade dilute hydrochloric acid is 0.4% of the weight of the solution of the temperature-sensitive polymer; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0135] The method for preparing the embolic material includes the following preparation steps:

[0136] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0137] Example 6

[0138] Preparation of temperature-sensitive polymers:

[0139] A temperature-sensitive polymer is a copolymer of N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage ratio of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 6.3 × 10⁻⁶. 4 The temperature-sensitive polymer further includes temperature-sensitive polymer-2; the degree of polymerization of temperature-sensitive polymer-2 is 1×10⁻⁶. 6 The weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 2.3:1.

[0140] The method for preparing the temperature-sensitive polymer includes the following steps:

[0141] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0142] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0143] (3) Preparation of temperature-sensitive polymer: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0144] (4) Preparation of temperature-sensitive polymer-2: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0145] Among them, the reaction temperature and time in steps (3) and (4) are different, and the degree of polymerization of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method;

[0146] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, wherein the weight ratio of sodium sulfite to potassium persulfate is 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0147] Preparation of embolic materials:

[0148] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent. The solvent is water for injection; the solution of the temperature-sensitive polymer further comprises 0.05 mol / L medical-grade dilute hydrochloric acid; the weight of the medical-grade dilute hydrochloric acid is 0.4% of the weight of the solution of the temperature-sensitive polymer; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0149] The method for preparing the embolic material includes the following preparation steps:

[0150] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0151] Example 7

[0152] Preparation of temperature-sensitive polymers:

[0153] A temperature-sensitive polymer is a copolymer of N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage ratio of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 6.3 × 10⁻⁶. 4 The temperature-sensitive polymer further includes temperature-sensitive polymer-2; the degree of polymerization of temperature-sensitive polymer-2 is 1×10⁻⁶. 7 The weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 2.3:1.

[0154] The temperature-sensitive polymer includes the following steps:

[0155] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0156] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0157] (3) Preparation of temperature-sensitive polymer: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0158] (4) Preparation of temperature-sensitive polymer-2: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0159] Among them, the reaction temperature and time in steps (3) and (4) are different, and the degree of polymerization of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method;

[0160] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, wherein the weight ratio of sodium sulfite to potassium persulfate is 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0161] Preparation of embolic materials:

[0162] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent. The solvent is water for injection; the solution of the temperature-sensitive polymer further comprises 0.05 mol / L medical-grade dilute hydrochloric acid; the weight of the medical-grade dilute hydrochloric acid is 0.4% of the weight of the solution of the temperature-sensitive polymer; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0163] The method for preparing the embolic material includes the following preparation steps:

[0164] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0165] Example 8

[0166] Preparation of temperature-sensitive polymers:

[0167] A temperature-sensitive polymer is a copolymer of N-isopropylacrylamide (NIP) and N-n-propylacrylamide (NNP) in a weight percentage range of 70:30; the degree of polymerization of the temperature-sensitive polymer-1 is 6.3 × 10⁻⁶. 4 The temperature-sensitive polymer further includes temperature-sensitive polymer-2; the degree of polymerization of temperature-sensitive polymer-2 is 4.8 × 10⁻⁶. 6 The weight ratio of temperature-sensitive polymer-1 to temperature-sensitive polymer-2 is 2.3:1.

[0168] The method for preparing the temperature-sensitive polymer includes the following steps:

[0169] (1) Preparation of N-isopropylacrylamide: Isopropylamine and ethyl acetate were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0170] (2) Preparation of N-n-propylacrylamide: n-propylamine and toluene were loaded into a reaction vessel and the reaction vessel was placed in an ice-water bath for cooling. Acrylamide chloride was added dropwise to the reaction vessel using a constant pressure dropping funnel. After the addition was completed, the reaction was carried out in ice water for 4 hours. After the reaction was completed, the reaction solution was filtered, the filtrate was collected, and the distillate was distilled under reduced pressure. The fraction was cooled to obtain N-isopropylacrylamide.

[0171] (3) Preparation of temperature-sensitive polymer: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0172] (4) Preparation of temperature-sensitive polymer-2: Weigh the corresponding weight percentages of N-isopropylacrylamide and N-n-propylacrylamide, mix them, add distilled water to dissolve them, add an initiator, carry out the polymerization reaction, after the reaction is complete, precipitate the polymer in water at 37°C to obtain a solid product, wash the solid product with distilled water to obtain the temperature-sensitive polymer.

[0173] Among them, the reaction temperature and time in steps (3) and (4) are different, and the degree of polymerization of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method;

[0174] The initiator comprises 14% of the weight of N-isopropylacrylamide; the initiator is sodium sulfite and potassium persulfate, wherein the weight ratio of sodium sulfite to potassium persulfate is 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

[0175] Preparation of embolic materials:

[0176] An embolization material comprising a solution of a temperature-sensitive polymer and a contrast agent; the solution of the temperature-sensitive polymer comprises a temperature-sensitive polymer and a solvent; the solvent is water for injection; the contrast agent is a water-soluble contrast agent; the water-soluble contrast agent is iohexol (iodine content 46.4%).

[0177] The method for preparing the embolic material includes the following preparation steps:

[0178] S1: Dissolve the temperature-sensitive polymer in a solvent to obtain a solution of the temperature-sensitive polymer; S2: Mix the solution of the temperature-sensitive polymer with a developer until homogeneous to obtain an embolic material.

[0179] Performance testing

[0180] 1. Viscosity test: The viscosity of the embolic material in the examples was tested using a viscometer at 20°C; Evaluation criteria: Viscosity less than or equal to 32 mPa·s and greater than or equal to 40 mPa·s is excellent; viscosity less than 32 mPa·s and greater than or equal to 18 mPa·s, or viscosity greater than 40 mPa·s and less than or equal to 50 mPa·s is good; viscosity less than 18 mPa·s or viscosity greater than 50 mPa·s is poor.

[0181] 2. Precipitation dispersion and in vitro conversion time test: A device mainly composed of a glass tube and a constant temperature water tank with a water pump was used. The constant temperature water tank provided a 36°C constant temperature environment for the glass tube. 12g of 2mm diameter glass beads were placed in a 10ml glass column, which was placed inside the constant temperature glass tube and connected to a saline bottle via a PVC pipe. The vertical distance between the saline and the glass column outlet was 150cm. A microcatheter was placed inside the glass column through a Y valve. The flow rate of the saline was adjusted to approximately 0.3ml / s. A 36°C constant temperature beaker was placed below the outlet. The embolic material was injected in portions through the microcatheter using a 1ml syringe. The precipitation dispersion of the embolic agent in the glass column was observed, as well as whether any precipitation flowed out through the glass column outlet. The time of precipitation appearance and the time of complete precipitation were observed and recorded.

[0182] Evaluation criteria for in vitro conversion time: A complete precipitation time of 50 s or more and 65 s or less is considered excellent; a complete precipitation time of 35 s or more and less than 50 s, or a complete precipitation time of 65 s or more and less than 85 s is considered good; a complete precipitation time of less than 35 s or 85 s or more is considered poor.

[0183] Evaluation criteria for sedimentation dispersion: Excellent sedimentation dispersion is characterized by the presence of sediment within the glass bead container that effectively fills the gaps between the glass beads, stopping the water flow through them, and no sediment overflowing from the top or bottom of the container. Good sedimentation dispersion is characterized by the presence of sediment within the glass bead container that fills the gaps between the glass beads, but a small amount of sediment overflows from the top or bottom of the container. Poor sedimentation dispersion is characterized by the presence of sediment within the glass bead container that does not fill the gaps between the glass beads, but a large amount of sediment overflows from the top or bottom of the container.

[0184] The test results are shown in Table 2:

[0185] Table 2

[0186]

[0187] The test results in Table 2 show that the embolic material prepared by the present invention using a certain amount of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 has good fluidity and in vitro conversion time, and its divergence performance is good.

[0188] The foregoing examples are merely illustrative, used to explain some features of the method described in this invention. The appended claims are intended to claim the broadest possible scope, and the embodiments presented herein are merely illustrative of selected implementations based on combinations of all possible embodiments. Therefore, the applicant intends that the appended claims are not limited by the selection of examples illustrating the features of the invention. Some numerical ranges used in the claims also include sub-ranges within them, and variations within these ranges should also be interpreted as being covered by the appended claims where possible.

Claims

1. An embolization material, characterized in that, The embolization material comprises a solution of temperature-sensitive polymer and a developing agent; the solution of temperature-sensitive polymer comprises temperature-sensitive polymer and solvent; the solvent is water for injection; the solution of temperature-sensitive polymer further comprises 0.05 mol / L of medical dilute hydrochloric acid; the weight of the medical dilute hydrochloric acid is 0.3% of the weight of the solution of temperature-sensitive polymer; the developing agent is a water-soluble developing agent; the water-soluble developing agent is iohexyl, and the iodine content is 46.4%; The preparation method of the embolization material comprises the following preparation steps: S1: dissolving temperature-sensitive polymer in solvent to obtain a solution of temperature-sensitive polymer; S2: stirring and mixing the solution of temperature-sensitive polymer and the developing agent uniformly to obtain the embolization material; The temperature-sensitive polymer is a polymer of which N-isopropyl acrylamide represented by NIP and N-n-propyl acrylamide represented by NNP are copolymerized at a weight ratio of 70:30; the temperature-sensitive polymer is composed of temperature-sensitive polymer-1 and temperature-sensitive polymer-2; the polymerization degree of the temperature-sensitive polymer-1 is 7.8 x 10 4 ; the polymerization degree of the temperature-sensitive polymer-2 is 4.2 x 10 6 ; and the weight ratio of the temperature-sensitive polymer-1 to the temperature-sensitive polymer-2 is 1.8:

1. The preparation method of the temperature-sensitive polymer comprises the following steps: (1) preparation of N-isopropyl acrylamide: loading isopropylamine and ethyl acetate into a reaction container, cooling the reaction container in an ice water bath, adding acryloyl chloride into the reaction container through a constant pressure dropping funnel, ice water reaction for 4 hours after the addition is completed, collecting the filtrate after the reaction is completed, and distilling under reduced pressure, and cooling the distillate to obtain N-isopropyl acrylamide; (2) preparation of N-n-propyl acrylamide: loading n-propylamine and toluene into a reaction container, cooling the reaction container in an ice water bath, adding acryloyl chloride into the reaction container through a constant pressure dropping funnel, ice water reaction for 4 hours after the addition is completed, collecting the filtrate after the reaction is completed, and distilling under reduced pressure, and cooling the distillate to obtain N-n-propyl acrylamide; (3) preparation of temperature-sensitive polymer-1: mixing N-isopropyl acrylamide and N-n-propyl acrylamide with a corresponding weight percentage, dissolving them in distilled water, adding an initiator, and performing polymerization reaction, and then precipitating the polymer in water at 37 DEG C to obtain a solid product, and washing the solid product with distilled water to obtain temperature-sensitive polymer-1; (4) preparation of temperature-sensitive polymer-2: mixing N-isopropyl acrylamide and N-n-propyl acrylamide with a corresponding weight percentage, dissolving them in distilled water, adding an initiator, and performing polymerization reaction, and then precipitating the polymer in water at 37 DEG C to obtain a solid product, and washing the solid product with distilled water to obtain temperature-sensitive polymer-2; In steps (3) and (4), the reaction temperature and time are different, and the polymerization degree of temperature-sensitive polymer-1 and temperature-sensitive polymer-2 is obtained by Ubbelohde viscometer method; The weight of the initiator is 14% of the weight of N-isopropyl acrylamide; the initiator is sodium sulfite and potassium persulfate, and the weight ratio of sodium sulfite to potassium persulfate is 1:3; the molar ratio of isopropylamine to acryloyl chloride is 2:1; the molar ratio of n-propylamine to acryloyl chloride is 2:1; the volume ratio of ethyl acetate to n-propylamine is 1:1; and the volume ratio of n-propylamine to toluene is 1:1.

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