CN114230678B - Photocrosslinked hydrogel embolism system for intravascular treatment and application method - Google Patents

Photocrosslinked hydrogel embolism system for intravascular treatment and application method Download PDF

Info

Publication number
CN114230678B
CN114230678B CN202111521041.1A CN202111521041A CN114230678B CN 114230678 B CN114230678 B CN 114230678B CN 202111521041 A CN202111521041 A CN 202111521041A CN 114230678 B CN114230678 B CN 114230678B
Authority
CN
China
Prior art keywords
carboxymethyl cellulose
solution
sodium carboxymethyl
sodium
photo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202111521041.1A
Other languages
Chinese (zh)
Other versions
CN114230678A (en
Inventor
戴冬伟
邢孟秋
刘建民
洪波
陈楚
李峥
金飞龙
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tongqiao Medical Technology Co ltd
Original Assignee
Zhuhai Tongqiao Medical Technology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhuhai Tongqiao Medical Technology Co ltd filed Critical Zhuhai Tongqiao Medical Technology Co ltd
Priority to CN202111521041.1A priority Critical patent/CN114230678B/en
Publication of CN114230678A publication Critical patent/CN114230678A/en
Application granted granted Critical
Publication of CN114230678B publication Critical patent/CN114230678B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B11/00—Preparation of cellulose ethers
    • C08B11/20—Post-etherification treatments of chemical or physical type, e.g. mixed etherification in two steps, including purification
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0031—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/08—Polysaccharides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Materials Engineering (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Surgery (AREA)
  • Biochemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a preparation method of sodium methyl cellulose acylate, which comprises the following steps: adding excessive aminoethyl methacrylamide hydrochloride into the sodium carboxymethyl cellulose solution, adjusting the pH value to 8.5, then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide, reacting for 100-280min at room temperature, purifying and drying to obtain sodium carboxymethyl cellulose methylacrylate. The invention also discloses a photo-crosslinking pregel solution, which comprises the following components: sodium carboxymethylcellulose (CMC), photocrosslinkers and developers. The invention also discloses a photocrosslinked hydrogel embolism system for intravascular treatment, which comprises: the photo-crosslinking pregel solution and a visible light source. The selected composition material greatly reduces toxicity and damage to organisms, can be quickly glued, and has ideal mechanical and swelling properties.

Description

Photocrosslinked hydrogel embolism system for intravascular treatment and application method
Technical Field
The invention relates to the technical field of medical instruments, in particular to sodium methacryloyl carboxymethyl cellulose and a preparation method thereof, a photo-crosslinking pregel solution, a photo-crosslinking hydrogel embolism system for intravascular treatment and a use method thereof.
Background
Intracranial aneurysms are abnormal distensions formed by gradual expansion of intracranial arterial blood vessels under the action of hemodynamic loads and other factors due to local vascular wall damage caused by congenital anomalies or acquired injuries and other factors. The intracranial aneurysm rupture hemorrhage has the advantages of urgent onset, severe symptoms, no obvious aura, and high mortality rate and disability rate.
The treatment of intracranial aneurysms is largely divided into surgical occlusion and endovascular interventional embolic treatment. But the surgical operation clamp has large wound, more complications and long operation and recovery time, and is not welcomed by doctors and patients. With the development and progress of minimally invasive endovascular interventional therapy, more and more intracranial aneurysm patients receive the endovascular interventional therapy, and the endovascular interventional embolic therapy is also becoming the dominant technology for intracranial aneurysm therapy. Embolism is a safe and reliable effective method for treating aneurysms, and is also a minimally invasive intravascular treatment method. Embolic material is inserted into the aneurysm through the catheter, blocking the blood supply results in ischemic necrosis of the aneurysm.
Traditional treatment methods use coils to fill the aneurysm, but this method suffers from the following drawbacks: 1. the operation difficulty is high, and the operation time is long; 2. the operation cost is high; 3. the low filling rate of the metallic coil results in the remaining volume being occupied by coagulated blood, and this uneven and incomplete filling of the aneurysm can lead to recanalization, rebleeding and rupture. Therefore, the use of coils is not suitable for patients with clotting problems (e.g. disseminated intravascular coagulation).
The use of liquid embolic agents, such as iodinated oil, N-butyl-2-cyanoacrylate (NBCA), and the Onyx liquid embolic system, is effective in solving some of the problems, and these liquid embolic agents can adequately fill aneurysms, provide good embolic effects, and occlude blood vessels at a rapid rate, and perform well in complex vascular environments. However, the existing liquid embolic agents still have some disadvantages:
1. requiring operators to have rich professional experience, if the operators are improperly operated, sticking pipes or self-curing easily occur, and serious complications are formed;
2. the components of the embolic agent contain toxic substances (such as dimethyl sulfoxide), and the too fast injection can cause vasospasm and necrosis;
3. the pricing of a portion of the embolic agent is high.
Hydrogels, which are a substance with good biocompatibility, good mechanical properties and swelling properties, can be considered as a potential liquid embolic material. Because of their soft mechanical strength, aneurysms can be tightly packed without damaging the vessel wall. The photocrosslinked hydrogel can be accurately conveyed to the aneurysm through the microcatheter, and can be quickly glued under the action of illumination, so that the aneurysm is fully filled, and the embolism effect is achieved. The researches and patents of the existing photocrosslinked hydrogel have the following defects: 1. part of the surface is glued by UV irradiation, which may cause DNA oxidative damage to tissues; 2. photocrosslinkers with certain toxicity are used, which are easy to cause tissue reaction.
Chinese patent CN 107754006A (application of the name of the invention of temperature responsive supramolecular copolymer hydrogel, publication date is 2018, 03 and 06) discloses that two monomers of acrylamide and N-acryloylchloride glycinamide are copolymerized under the action of initiator to obtain polymer gel. The polymer gel is mixed with iohexol at high temperature to obtain a homogeneous mixture. The hydrogel containing iohexol can be injected into renal arteries through a microcatheter in a molten state slightly higher than the body temperature to embolize the kidneys, and can be applied to embolizing large arteries. The hydrogel mixture can undergo sol-gel transition near the temperature of the human body, and the iohexol-containing polymer can be developed under X-rays, which helps the embolic material to smoothly enter the target site. However, such temperature-responsive hydrogels are limited by temperature, and the instability of sol and gel formation is large, and gel is likely to occur during the transportation of the microcatheter in the human body, so that the microcatheter is blocked and cannot be transported continuously, and the gel formed by the orifice is also likely to adhere to the tube, so that the method is difficult to realize clinically.
Chinese patent CN 107875436A (entitled "composition of liquid embolic agent loaded with baking soda powder" and its use, publication date is 2017, 11, 10) discloses that the obtained liquid embolic agent is composed of an anionically modified polyethylene-polyvinyl alcohol copolymer (EVOH), a solvent, baking soda powder and a developer mixed in a certain proportion. EVOH introduces negative ion groups on a high molecular chain through a chemical modification or grafting modification method, and the negative ion groups can adsorb and load cationized chemotherapeutic anticancer drugs through interaction of positive and negative charges. The solvent may be dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), ethanol or a mixture thereof. The developer is micron-sized tantalum metal powder or iodine-containing photographic agent or a mixture thereof. The baking soda can sensitize the ischemia effect of tumor cells, thereby improving the embolism curative effect. The patent is an improvement on the basis of Oynx glue, but the patent still has the problems of containing toxic solvents and being easy to self-cure to cause complications, so that the patent is also not an ideal liquid embolic material.
Chinese patent CN 107043467A (entitled photo-crosslinkable hydrogel and method for preparing same, publication date 2020, month, 19) discloses that the substrate of the hydrogel comprises keratin, and the keratin contains a plurality of free sulfhydryl groups. The preparation method comprises the following steps: dissolving keratin in a buffer solution, adding a photoinitiator, fully dissolving, and then, irradiating under an ultraviolet lamp to form the photo-crosslinkable hydrogel. However, the photocrosslinked hydrogel uses ultraviolet light as a light source, and the ultraviolet wavelength has high cytotoxicity potential and is easy to cause DNA oxidative damage. Therefore, such photocrosslinked hydrogels are also not ideal liquid embolic materials.
Disclosure of Invention
In order to solve the defects in the prior art, a photocrosslinked hydrogel embolic system for intravascular treatment is provided.
The invention aims at providing a preparation method of sodium carboxymethyl cellulose methylacrylate, which comprises the following steps: adding excessive aminoethyl methacrylamide hydrochloride into the sodium carboxymethyl cellulose solution, adjusting the pH value to 8.5, then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide, reacting for 100-280min at room temperature, purifying and drying to obtain sodium carboxymethyl cellulose methylacrylate.
Sodium carboxymethyl cellulose (CMC) is a carboxymethylated derivative of cellulose, is a water-soluble linear polysaccharide, has good film-forming property and good biocompatibility, and is often used as an anti-adhesion material and a hemostatic material.
Preferably, the sodium carboxymethyl cellulose solution is obtained by dissolving sodium carboxymethyl cellulose in sodium bicarbonate buffer.
Preferably, the mass volume ratio g/mL of the sodium carboxymethyl cellulose solution is 0.005-0.10.
Preferably, the molar ratio of aminoethylmethacrylamide hydrochloride to 1-ethyl- (3-dimethylaminopropyl) carbodiimide is always 1:1.
preferably, the purification is a dialysis purification to remove solvent small molecules.
Preferably, the drying is freeze-drying.
Specifically, sodium carboxymethyl cellulose (CMC) was dissolved in a sodium bicarbonate buffer to obtain a sodium carboxymethyl cellulose solution, an excess of aminoethylmethacrylate hydrochloride (AEM) was added to the sodium carboxymethyl cellulose solution, and then sodium hydroxide was added to adjust the pH to 8.5. 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) in an equimolar amount to aminoethylmethacrylamide hydrochloride was added to the above solution and reacted at room temperature for 2 hours. Then, aminoethylmethacrylamide hydrochloride (AEM) and 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) were added to the reaction mixture, and the reaction was continued for 2 hours to obtain a product. And (3) dialyzing and purifying the product to remove solvent micromolecules, and then performing freeze drying treatment to obtain powdered sodium methylacryloylcarboxymethylcellulose (CMC-MA).
The second object of the present invention is to provide sodium methacryloyl carboxymethyl cellulose, which is obtained by the above-mentioned method for producing sodium methacryloyl carboxymethyl cellulose.
It is a further object of the present invention to provide a photo-crosslinking pregel solution comprising: sodium carboxymethylcellulose (CMC), photocrosslinkers and developers.
Specifically, the sodium methylacryloyl carboxymethylcellulose is prepared by modifying and grafting the side chain end group of sodium carboxymethylcellulose, adding a photosensitive group (methacryloyl (-MA), purifying and freeze-drying; the photocrosslinker is a safe photocrosslinker that has been demonstrated in biomedical applications; the imaging substance is a non-radiolucent substance.
Preferably, the mass volume ratio (g/mL) of the sodium methacryloyl carboxymethylcellulose is 0.03-0.20, the mass volume ratio (g/mL) of the photo-crosslinking agent is 0.03-0.05, and the mass volume ratio (g/mL) of the developer is 0.10.
Preferably, the photocrosslinking agent is at least one of eosin-Y, triethanolamine, N-vinylcaprolactam.
Preferably, the photocrosslinker consists of eosin-Y, triethanolamine and N-vinylcaprolactam, and the mass ratio of eosin-Y, triethanolamine and N-vinylcaprolactam is 3:188:125.
the visible light photosensitizer eosin-Y is a safe photocrosslinking system approved by the U.S. food and drug administration that has been demonstrated in biomedical applications, the triplet state of eosin Y being able to accept hydrogen atoms from the co-initiator Triethanolamine (TEA) during polymerization, while the copolymer N-Vinylcaprolactam (VC) can accelerate gelation. These properties make visible light suitable for use in situ crosslinked photocrosslinked hydrogels.
Preferably, the developer is at least one of tantalum powder, iohexol, iodixanol, iopamidol.
The selected composition material greatly reduces toxicity and damage to organisms, can be quickly glued, and has ideal mechanical and swelling properties.
Compared with the existing research, the invention has the following advantages:
1. the harmless light source and the nontoxic photo-crosslinking agent reduce the damage to organisms, while the ultraviolet light is used for crosslinking in the past, and the ultraviolet light can cause DNA oxidative damage to human tissues;
2. the water-soluble sodium carboxymethyl cellulose is adopted to carry out side chain end group modification grafting, and a photosensitive group is added, so that the use of toxic organic solvents (such as DMSO) is avoided;
2. the obtained sodium methacryloyl carboxymethylcellulose, the photo-crosslinking agent and the developer can be stably kept in a liquid state before photo-crosslinking, and can not be self-solidified in the conveying process; under the irradiation of visible light, the photosensitive group-methacryloyl (-MA) contained in the sodium carboxymethylcellulose is subjected to free radical reaction with another photosensitive group under the assistance of photo-crosslinking agents such as eosin Y, triethanolamine and N-vinylcaprolactam, and photo-crosslinking in-situ gel formation is carried out to obtain a hydrogel network; when the light source is stopped, the gel formation is stopped, and the adverse phenomena of the hydrogel gluing pipe and self-curing are avoided;
3. the gel forming is quick, and the operation time and the operation cost are reduced.
It is a fourth object of the present invention to provide a photocrosslinked hydrogel embolization system for intravascular treatment, comprising: the photo-crosslinking pregel solution and a visible light source.
Preferably, the light source is harmless visible light of 400-600 nm.
The fifth object of the present invention is to provide a method for using the above photocrosslinked hydrogel embolic system for intravascular treatment, comprising: the photocrosslinking pregel solution and a microcatheter for delivering the photocrosslinking pregel solution are provided, wherein the microcatheter comprises an optical fiber and an inner catheter for delivering the photocrosslinking pregel solution;
and (3) conveying the photo-crosslinked pregelatinized solution from the inner catheter into a human body to accurately find the position of an aneurysm, then injecting the photo-crosslinked pregelatinized solution from the micro-catheter, and exposing the photo-crosslinked pregelatinized solution to visible light emitted from an optical fiber at a specific angle when the slender pregelatinized solution flows to a single-lumen outlet of the micro-catheter, wherein the photo-crosslinked pregelatinized solution is subjected to in-situ photo-crosslinking to quickly form linear hydrogel, so that the linear hydrogel is fully filled in the inner cavity of the aneurysm, and the therapeutic effect of embolism is achieved.
Drawings
FIG. 1 is a schematic flow chart of a method for using a photocrosslinked hydrogel embolic system for intravascular treatment according to the present invention.
Detailed Description
The invention is further illustrated below in connection with specific embodiments.
Example 1
The preparation method of the carboxymethyl cellulose-methacrylate grafted compound comprises the following steps:
1. a solution of sodium carboxymethyl cellulose (CMC) was prepared in 50mmol/L, pH =8.5 sodium bicarbonate buffer, then the aminoethylmethacrylate hydrochloride (AEM) was added in excess, the molar ratio of carboxylic acid groups of sodium carboxymethyl cellulose to aminoethylmethacrylate hydrochloride being 1:3, a step of;
2. readjust the pH to 8.5 using 1mol/L sodium hydroxide;
3. then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) with the same molar quantity as that of the aminoethylmethacrylamide hydrochloride (AEM) into the solution, and carrying out reaction for 2 hours at room temperature;
4. then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and aminoethylmethacrylate hydrochloride (AEM) reactant again for reacting for 2 hours;
wherein, the addition amount of the 1-ethyl- (3-dimethylaminopropyl) carbodiimide and the aminoethylmethacrylamide hydrochloride in the step 4 is consistent with the addition amounts of the aminoethylmethacrylamide hydrochloride in the step 1 and the 1-ethyl- (3-dimethylaminopropyl) carbodiimide in the step 3;
5. the product sodium carboxymethylcellulose is obtained, purified by dialysis and then freeze-dried, and the carboxymethyl cellulose-methacrylate grafted compound is obtained.
Example 2
The preparation method of the carboxymethyl cellulose-methacrylate grafted compound comprises the following steps:
1. a solution of sodium carboxymethyl cellulose (CMC) was prepared in 50mmol/L, pH =8.5 sodium bicarbonate buffer and then the aminoethylmethacrylamide hydrochloride (AEM) was added in excess in a molar ratio of carboxylic acid groups of sodium carboxymethyl cellulose to aminoethylmethacrylamide hydrochloride of 1:5, a step of;
2. readjust the pH to 8.5 using 1mol/L sodium hydroxide;
3. then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) with the same molar quantity as that of the aminoethylmethacrylamide hydrochloride (AEM) into the solution, and carrying out reaction for 2 hours at room temperature;
4. then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and aminoethylmethacrylate hydrochloride (AEM) reactant again for reacting for 2 hours;
wherein, the addition amount of the 1-ethyl- (3-dimethylaminopropyl) carbodiimide and the aminoethylmethacrylamide hydrochloride in the step 4 is consistent with the addition amounts of the aminoethylmethacrylamide hydrochloride in the step 1 and the 1-ethyl- (3-dimethylaminopropyl) carbodiimide in the step 3;
5. the product sodium carboxymethylcellulose is obtained, purified by dialysis and then freeze-dried, and the carboxymethyl cellulose-methacrylate grafted compound is obtained.
Example 3
The preparation method of the carboxymethyl cellulose-methacrylate grafted compound comprises the following steps:
1. a solution of sodium carboxymethyl cellulose (CMC) was prepared in 50mmol/L, pH =8.5 sodium bicarbonate buffer and then the aminoethylmethacrylate hydrochloride (AEM) was added in excess in a molar ratio of carboxylic acid groups of sodium carboxymethyl cellulose to aminoethylmethacrylate hydrochloride of 1:5, a step of;
2. readjust the pH to 8.5 using 1mol/L sodium hydroxide;
3. then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) with the same molar quantity as that of the aminoethylmethacrylamide hydrochloride (AEM) into the solution, and carrying out a reaction for 4 hours at room temperature;
4. then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and aminoethylmethacrylate hydrochloride (AEM) reactant again for reacting for 4 hours;
wherein, the addition amount of the 1-ethyl- (3-dimethylaminopropyl) carbodiimide and the aminoethylmethacrylamide hydrochloride in the step 4 is consistent with the addition amounts of the aminoethylmethacrylamide hydrochloride in the step 1 and the 1-ethyl- (3-dimethylaminopropyl) carbodiimide in the step 3;
5. the product sodium carboxymethylcellulose is obtained, purified by dialysis and then freeze-dried, and the carboxymethyl cellulose-methacrylate grafted compound is obtained.
Example 4
The preparation method of the carboxymethyl cellulose-methacrylate grafted compound comprises the following steps:
1. a solution of sodium carboxymethyl cellulose (CMC) was prepared in 50mmol/L, pH =8.5 sodium bicarbonate buffer and then the aminoethylmethacrylate hydrochloride (AEM) was added in excess in a molar ratio of carboxylic acid groups of sodium carboxymethyl cellulose to aminoethylmethacrylate hydrochloride of 1:10;
2. readjust the pH to 8.5 using 1mol/L sodium hydroxide;
3. then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) with the same molar quantity as that of the aminoethylmethacrylamide hydrochloride (AEM) into the solution, and carrying out reaction for 8 hours at room temperature;
4. the product sodium carboxymethylcellulose is obtained, purified by dialysis and then freeze-dried, and the carboxymethyl cellulose-methacrylate grafted compound is obtained.
Example 5
A photo-crosslinked pregel solution comprising: the carboxymethyl cellulose-methacrylate grafted compound obtained in the above example has a mass-volume ratio of 0.03g/mL, the photo-crosslinking agent has a mass-volume ratio of 0.05g/mL, and the tantalum powder has a mass-volume ratio of 0.10 g/mL.
The photo-crosslinking agent comprises eosin-Y, triethanolamine and N-vinyl caprolactam according to a mass ratio of 3:188:125.
Example 6
A photo-crosslinked pregel solution comprising: the carboxymethyl cellulose-methacrylate grafted compound obtained in the above example has a mass-volume ratio of 0.20g/mL, the photo-crosslinking agent has a mass-volume ratio of 0.03g/mL, and the iohexol has a mass-volume ratio of 0.10 g/mL.
The photo-crosslinking agent comprises eosin-Y, triethanolamine and N-vinyl caprolactam according to a mass ratio of 3:188:125.
Example 7
A photo-crosslinked pregel solution comprising: the carboxymethyl cellulose-methacrylate grafted compound obtained in the above example has a mass-volume ratio of 0.10g/mL, the photo-crosslinking agent has a mass-volume ratio of 0.04g/mL, and the iodixanol has a mass-volume ratio of 0.10 g/mL.
The photo-crosslinking agent comprises eosin-Y, triethanolamine and N-vinyl caprolactam according to a mass ratio of 3:188:125.
Example 8
Referring to fig. 1, fig. 1 is a schematic flow chart of a method for using a photocrosslinked hydrogel embolization system for intravascular treatment according to the present invention.
A method of using a photocrosslinked hydrogel embolic system for intravascular treatment, comprising: the photocrosslinking pregel solution and a microcatheter for delivering the photocrosslinking pregel solution are provided, wherein the microcatheter comprises an optical fiber and an inner catheter for delivering the photocrosslinking pregel solution;
and (3) conveying the photo-crosslinked pregelatinized solution from the inner catheter into a human body to accurately find the position of an aneurysm, then injecting the photo-crosslinked pregelatinized solution from the micro-catheter, and exposing the photo-crosslinked pregelatinized solution to visible light emitted from an optical fiber at a specific angle when the slender pregelatinized solution flows to a single-lumen outlet of the micro-catheter, wherein the photo-crosslinked pregelatinized solution is subjected to in-situ photo-crosslinking to quickly form linear hydrogel, so that the linear hydrogel is fully filled in the inner cavity of the aneurysm, and the therapeutic effect of embolism is achieved.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.

Claims (4)

1. A photocrosslinked pregel solution for intravascular treatment comprising: sodium methacryloyl carboxymethylcellulose, photocrosslinkers, and developers;
the preparation method of the sodium carboxymethyl cellulose methacrylate comprises the following steps: dissolving sodium carboxymethyl cellulose in sodium bicarbonate buffer solution to obtain sodium carboxymethyl cellulose solution, adding excessive aminoethyl methacrylamide hydrochloride into the sodium carboxymethyl cellulose solution, regulating the pH value to 8.5, then adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide, reacting for 100-280min at room temperature, and then purifying and drying to obtain sodium carboxymethyl cellulose methylacrylate;
the mass volume ratio g/mL of the sodium methacryloyl carboxymethylcellulose is 0.03-0.20, the mass volume ratio g/mL of the photo-crosslinking agent is 0.03-0.05, and the mass volume ratio g/mL of the developer is 0.10;
the photocrosslinking agent is at least one of eosin-Y, triethanolamine and N-vinyl caprolactam; the developer is at least one of tantalum powder, iohexol, iodixanol and iopamidol.
2. The photocrosslinked pregelatinized solution for intravascular treatment according to claim 1 characterized in that the mass to volume ratio g/mL of sodium carboxymethyl cellulose solution is 0.005-0.10.
3. The photocrosslinked pregel solution for intravascular treatment according to claim 1 characterized in that the molar ratio of aminoethylmethacrylamide hydrochloride to 1-ethyl- (3-dimethylaminopropyl) carbodiimide is always 1:1.
4. the photocrosslinked pregel solution for intravascular treatment according to claim 1 wherein the purification is purification by dialysis to remove solvent small molecules and the drying is lyophilization.
CN202111521041.1A 2021-12-13 2021-12-13 Photocrosslinked hydrogel embolism system for intravascular treatment and application method Active CN114230678B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111521041.1A CN114230678B (en) 2021-12-13 2021-12-13 Photocrosslinked hydrogel embolism system for intravascular treatment and application method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111521041.1A CN114230678B (en) 2021-12-13 2021-12-13 Photocrosslinked hydrogel embolism system for intravascular treatment and application method

Publications (2)

Publication Number Publication Date
CN114230678A CN114230678A (en) 2022-03-25
CN114230678B true CN114230678B (en) 2023-09-01

Family

ID=80755336

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111521041.1A Active CN114230678B (en) 2021-12-13 2021-12-13 Photocrosslinked hydrogel embolism system for intravascular treatment and application method

Country Status (1)

Country Link
CN (1) CN114230678B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115025384A (en) * 2022-05-24 2022-09-09 华中科技大学 Intelligent microneedle patch with mathematical simulation optimized shading and preparation method thereof

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4708821A (en) * 1985-03-27 1987-11-24 Hoechst Gosei Kabushiki Kaisha Process for preparing aqueous gel and use thereof
US6734298B1 (en) * 1998-11-11 2004-05-11 Farmila-Thea Faraceutici S.P.A. Cross-linking process of carboxylated polysaccharides
EP1992364A1 (en) * 2007-05-16 2008-11-19 Biosuma S.r.l. Carboxylated polysaccharides phosphated or bisphosphonated derivatives, optionally cross-linked, and their preparation and biomedical uses
WO2010009938A1 (en) * 2008-07-24 2010-01-28 L'oreal Polymers with polysaccharide grafts, cosmetic compositions and treatment method
CN103408702A (en) * 2013-07-09 2013-11-27 上海东升新材料有限公司 Preparation method of graft-polymer cationic dry strength agent
CN106317263A (en) * 2016-08-23 2017-01-11 浙江理工大学 Visible light initiating system in medical photo-curing hydrogel and photo-curing method thereof
JP2019035043A (en) * 2017-08-18 2019-03-07 株式会社クラレ Stimulus-curable gel
CN109942752A (en) * 2019-03-22 2019-06-28 华南农业大学 Modified carboxy methyl cellulose biocompatibility composite hydrogel precursor liquid, composite hydrogel and its application
WO2021007899A1 (en) * 2019-07-15 2021-01-21 浙江工业大学 Injectable hydrogel material and preparation method therefor and use thereof
CN112442141A (en) * 2019-09-04 2021-03-05 山东陆海蓝圣生物科技股份有限公司 Aminopyridine-containing carboxymethyl chitosan and preparation method and application thereof
CN112513212A (en) * 2018-08-09 2021-03-16 三菱化学株式会社 Photocurable adhesive sheet, laminate for image display device, and image display device
CN213130115U (en) * 2020-08-06 2021-05-07 华夏司印(上海)生物技术有限公司 Osteochondral scaffold
CN113461974A (en) * 2021-07-28 2021-10-01 吉林大学 Gas response surface lubricating hydrogel and preparation method thereof
CN113456303A (en) * 2020-08-06 2021-10-01 华夏司印(上海)生物技术有限公司 Osteochondral scaffold and preparation method and application thereof
WO2022061254A1 (en) * 2020-09-18 2022-03-24 Lan Li Methacrylated nanoparticles and related method

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210307760A1 (en) * 2008-05-01 2021-10-07 Aneuclose Llc Intrasacular Aneurysm Occlusion Device with a Flexible Net or Mesh and Polymer Longitudinal Embolic Members
CN112266367B (en) * 2017-11-15 2023-12-08 中山光禾医疗科技有限公司 Preparation, raw materials, products and application of photocrosslinked hydrogel material
FI3727488T3 (en) * 2017-12-18 2023-09-07 Univ Aveiro Hydrogels based on blood plasma components, process and uses thereof

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4708821A (en) * 1985-03-27 1987-11-24 Hoechst Gosei Kabushiki Kaisha Process for preparing aqueous gel and use thereof
US6734298B1 (en) * 1998-11-11 2004-05-11 Farmila-Thea Faraceutici S.P.A. Cross-linking process of carboxylated polysaccharides
EP1992364A1 (en) * 2007-05-16 2008-11-19 Biosuma S.r.l. Carboxylated polysaccharides phosphated or bisphosphonated derivatives, optionally cross-linked, and their preparation and biomedical uses
WO2010009938A1 (en) * 2008-07-24 2010-01-28 L'oreal Polymers with polysaccharide grafts, cosmetic compositions and treatment method
CN103408702A (en) * 2013-07-09 2013-11-27 上海东升新材料有限公司 Preparation method of graft-polymer cationic dry strength agent
CN106317263A (en) * 2016-08-23 2017-01-11 浙江理工大学 Visible light initiating system in medical photo-curing hydrogel and photo-curing method thereof
JP2019035043A (en) * 2017-08-18 2019-03-07 株式会社クラレ Stimulus-curable gel
CN112513212A (en) * 2018-08-09 2021-03-16 三菱化学株式会社 Photocurable adhesive sheet, laminate for image display device, and image display device
CN109942752A (en) * 2019-03-22 2019-06-28 华南农业大学 Modified carboxy methyl cellulose biocompatibility composite hydrogel precursor liquid, composite hydrogel and its application
WO2021007899A1 (en) * 2019-07-15 2021-01-21 浙江工业大学 Injectable hydrogel material and preparation method therefor and use thereof
CN112442141A (en) * 2019-09-04 2021-03-05 山东陆海蓝圣生物科技股份有限公司 Aminopyridine-containing carboxymethyl chitosan and preparation method and application thereof
CN213130115U (en) * 2020-08-06 2021-05-07 华夏司印(上海)生物技术有限公司 Osteochondral scaffold
CN113456303A (en) * 2020-08-06 2021-10-01 华夏司印(上海)生物技术有限公司 Osteochondral scaffold and preparation method and application thereof
WO2022061254A1 (en) * 2020-09-18 2022-03-24 Lan Li Methacrylated nanoparticles and related method
CN113461974A (en) * 2021-07-28 2021-10-01 吉林大学 Gas response surface lubricating hydrogel and preparation method thereof

Also Published As

Publication number Publication date
CN114230678A (en) 2022-03-25

Similar Documents

Publication Publication Date Title
JP6058056B2 (en) Non-degradable, low-swelling, water-soluble, radiopaque hydrogel
JP5438878B2 (en) Methods to prevent the formation of endoleaks associated with endovascular repair of celiac aortic aneurysms
Horak et al. Hydrogels in endovascular embolization. III. Radiopaque spherical particles, their preparation and properties
US6531111B1 (en) High viscosity embolizing compositions
US7459142B2 (en) High viscosity embolizing compositions comprising prepolymers
DE60130544T2 (en) EMBOLIC COMPOSITIONS
JP5559068B2 (en) Kit and delivery device for occlusion of body lumen
US7914541B2 (en) In situ materials formation
CN105209075B (en) Biocompatible in situ hydrogels
US11759553B2 (en) Method for forming hydrogels and materials therefor
CN114230678B (en) Photocrosslinked hydrogel embolism system for intravascular treatment and application method
JP6533776B2 (en) System for treating an aneurysm in a patient's body and method of operating the same
US8048407B2 (en) In situ gelling self-reactive materials for embolization
Soga et al. Calcium alginate provides a high degree of embolization in aneurysm models: A specific comparison to coil packing

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
CB03 Change of inventor or designer information

Inventor after: Dai Dongwei

Inventor after: Xing Mengqiu

Inventor after: Liu Jianmin

Inventor after: Hong Bo

Inventor after: Chen Chu

Inventor after: Li Zheng

Inventor after: Jin Feilong

Inventor before: Dai Dongwei

Inventor before: Li Zheng

Inventor before: Jin Feilong

Inventor before: Xie Guangchao

CB03 Change of inventor or designer information
GR01 Patent grant
GR01 Patent grant
CP03 Change of name, title or address

Address after: 519000 Zhuhai City, Guangdong Province, Xiangzhou District, Tangjiawan Town Science and Technology 7 Road No. 1 Zhuhai Medium-Electricity High-tech Industrial Park, 4 1-B Units

Patentee after: Tongqiao Medical Technology Co.,Ltd.

Country or region after: China

Address before: 519000 Zhuhai City, Guangdong Province, Xiangzhou District, Tangjiawan Town Science and Technology 7 Road No. 1 Zhuhai Medium-Electricity High-tech Industrial Park, 4 1-B Units

Patentee before: ZHUHAI TONGQIAO MEDICAL TECHNOLOGY CO.,LTD.

Country or region before: China