CN114409932A - Preparation method and application of intraoperative gastric filling hydrogel - Google Patents

Preparation method and application of intraoperative gastric filling hydrogel Download PDF

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Publication number
CN114409932A
CN114409932A CN202210238443.9A CN202210238443A CN114409932A CN 114409932 A CN114409932 A CN 114409932A CN 202210238443 A CN202210238443 A CN 202210238443A CN 114409932 A CN114409932 A CN 114409932A
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Prior art keywords
hydrogel
organic acid
acid salt
intraoperative
preparing
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吴德群
李永勇
任天斌
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Jiangsu Jicui Functional Material Research Institute Co ltd
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Jiangsu Jicui Functional Material Research Institute Co ltd
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    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00Processes of treating or compounding macromolecular substances
    • C08J3/02Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075Macromolecular gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52Hydrogels or hydrocolloids
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/04Alginic acid; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00Use of inorganic substances as compounding ingredients
    • C08K3/30Sulfur-, selenium- or tellurium-containing compounds
    • C08K2003/3045Sulfates
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00Use of organic ingredients
    • C08K5/04Oxygen-containing compounds
    • C08K5/09Carboxylic acids; Metal salts thereof; Anhydrides thereof
    • C08K5/098Metal salts of carboxylic acids

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Polymers & Plastics (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to the field of IPC classified A61L27/00, in particular to a preparation method and application of intra-operative stomach filling hydrogel. A preparation method of intraoperative gastric filling hydrogel at least comprises the following steps: (1) preparing an organic acid salt solution; (2) preparing an adjuvant solution; (3) mixing the components in proportion. According to the preparation method of the intraoperative gastric filling hydrogel provided by the invention, the prepared hydrogel has good mechanical strength and biocompatibility, the phenomenon that the hydrogel is blocked due to premature gelation in the injection process of an injector is effectively avoided, and the preparation method is suitable for popularization in the medical field.

Description

Preparation method and application of intraoperative gastric filling hydrogel
Technical Field
The invention relates to the field of IPC classified A61L27/00, in particular to a preparation method and application of intra-operative stomach filling hydrogel.
Background
Tissue engineering, which is an engineering technology widely studied in recent years, is widely used in life science, and among them, hydrogel, which is a tissue engineering component commonly used in the medical field, is widely used in medical repair, maintenance, and biological replacement of functions and forms after various tissues or organs of a human body are damaged. The hydrogel of the alginate is used for a support member and a protection member in medical surgery because of its excellent porosity, biocompatibility, and the like.
The prior art (CN111888524A) provides a tissue filling material, which mainly uses alginate and metal cation cross-linking agent to prepare the filling material, and claims that the prepared product has cell nutrient substance filling effect and human tissue and cell vitality improving effect, but during the actual use process, the mixture of multiple components can form solidified gel in a container prematurely when a syringe is injected, thereby blocking the syringe and influencing the normal use and operation process of the hydrogel.
Therefore, there is a need for a hydrogel preparation and use method that has good support and biocompatibility while effectively avoiding premature gel blocking during surgical use.
Disclosure of Invention
In order to solve the above problems, the present invention provides, in a first aspect, a method for preparing an intraoperative gastric filling hydrogel, comprising at least the following steps: (1) preparing an organic acid salt solution; (2) preparing an adjuvant solution; (3) mixing the components in proportion.
As a preferable scheme, the organic acid salt is at least one of sodium alginate, calcium alginate, potassium alginate and lithium alginate.
As a preferable scheme, the organic acid salt is sodium alginate.
As a preferred embodiment, the preparation of the organic acid salt comprises the following specific operations: adding the organic acid salt into deionized water, and violently stirring for 2-4 hours until the organic acid salt is completely dissolved to obtain an organic acid salt solution.
As a preferable scheme, the mass ratio of the organic acid salt to the deionized water is 0.1-1: 80-120 parts.
As a preferred scheme, the mass ratio of the organic acid salt to the deionized water is 1: 100.
preferably, the adjuvant is calcium gluconate and/or calcium sulfate.
Preferably, the adjuvant is calcium sulfate.
As a preferred embodiment, the preparation of the adjuvant solution is carried out in the following manner: and adding the auxiliary agent into deionized water, and stirring vigorously for 2-4 hours until the auxiliary agent is completely dissolved to obtain an auxiliary agent solution.
As a preferable scheme, the mass ratio of the auxiliary agent to the deionized water is 0.1-0.5: 80-120 parts.
As a preferred scheme, the mass ratio of the auxiliary agent to the deionized water is 0.26 ± 0.005: 100.
as a preferred scheme, the specific operations of the proportioning mixing preparation are as follows: and respectively sucking the organic acid salt solution and the adjuvant solution by using different injectors, simultaneously injecting the organic acid salt solution and the adjuvant solution into a mold according to a fixed volume ratio, quickly and uniformly mixing, and standing for 1-20 minutes to obtain the hydrogel.
Preferably, the volume ratio of the organic acid salt solution to the adjuvant solution is 1-10: 1-10.
Preferably, the volume ratio of the organic acid salt solution to the adjuvant solution is 2-4: 1-2.
In a preferred embodiment, the volume ratio of the organic acid salt solution to the adjuvant solution is 3: 1.
In a second aspect, the invention provides an application of the hydrogel prepared by the preparation method of the intra-operative gastric filling hydrogel, including an application of the hydrogel in filling in gastric surgery.
Has the advantages that:
1. according to the hydrogel provided by the application, the hydrogel is prepared on the basis of basic raw materials, other chemicals are not additionally added, the prepared hydrogel contains a large amount of hydrogen bond effects, and the tight chain entanglement of a polymer chain caused by ionic crosslinking, so that the crosslinking synergistic effect between the polymer chain and metal ions is fully exerted, and the mechanical property of the hydrogel is obviously improved.
2. According to the hydrogel provided by the application, on the basis of hydrogel preparation, specific preparation raw materials are selected by controlling, and the mass and volume ratio among the specific raw materials are controlled, so that the coagulation and solidification rate of the hydrogel is effectively controlled, and particularly, when the volume ratio of an organic acid salt solution to an auxiliary solution is 3:1, and the mass ratio of the organic acid salt to deionized water is 1: 100 hours, the system can effectively avoid the phenomenon of injector blockage caused by premature gelation in the injection process of hydrogel in the prior art, and prevent the phenomenon from influencing the operation process.
Detailed Description
Example 1
Example 1 in a first aspect, a method is provided for preparing an intraoperative gastric filling hydrogel, comprising the steps of: (1) preparing an organic acid salt solution; (2) preparing an adjuvant solution; (3) mixing the components in proportion.
The specific operation of preparing the organic acid salt is as follows: adding the organic acid salt into deionized water, and violently stirring for 3 hours until the organic acid salt is completely dissolved to obtain an organic acid salt solution.
The specific operations for the preparation of the adjuvant solution are: adding the adjuvant into deionized water, and stirring vigorously for 3 hours until the adjuvant is completely dissolved to obtain adjuvant solution.
The specific operation of proportioning and mixing preparation is as follows: respectively sucking the organic acid salt solution and the adjuvant solution by different injectors, simultaneously injecting the organic acid salt solution and the adjuvant solution into a mold according to a fixed volume ratio, quickly and uniformly mixing, and standing for 30 minutes to obtain the hydrogel.
The organic acid salt is sodium alginate; the mass ratio of the organic acid salt to the deionized water is 1: 100.
the adjuvant is calcium gluconate; the mass ratio of the auxiliary agent to the deionized water is 0.26: 100.
the volume ratio of the organic acid salt solution to the adjuvant solution was 3: 1.
Example 2
The embodiment of the present invention is different from embodiment 1 in that:
the mass ratio of the organic acid salt to the deionized water is 0.8: 100.
the mass ratio of the auxiliary agent to the deionized water is 0.15: 100.
the volume ratio of the organic acid salt solution to the adjuvant solution was 2.5: 1.
Example 3
The embodiment of the present invention is different from embodiment 1 in that:
the auxiliary agent is calcium sulfate; the mass ratio of the auxiliary agent to the deionized water is 0.26 +/-0.005: 100.
comparative example 1
The embodiment of this comparative example is the same as example 1 except that:
the mass ratio of the organic acid salt to the deionized water is 1.5: 100.
the mass ratio of the auxiliary agent to the deionized water is 2: 100.
comparative example 2
The embodiment of this comparative example is the same as example 1 except that:
the volume ratio of the organic acid salt solution to the adjuvant solution was 3: 0.5.
Evaluation of Performance
Mechanical properties: cylindrical hydrogels (diameter 7mm, height 8.5mm) prepared in examples and comparative examples were uniformly coated with vaseline on the surface to prevent a large amount of dehydration, and then tensile strength of the hydrogels was measured using a universal mechanical tester, and compressive strength of the hydrogels was measured by compressing the hydrogels at a speed of 1mm/min, 10 samples were tested for each comparative example of examples, and the average value of the measured values is shown in Table 1.
Gelling phenomenon: hydrogels were prepared by the methods provided in examples and comparative examples, respectively, and injected into the bionic tissue after the preparation was completed, the injection tube phenomenon during the injection process and the formation result of the hydrogel reaching the inside of the tissue were observed, the coagulation gelling time of the hydrogel was observed, and the measured results are reported in table 1.
TABLE 1
Examples Gel forming time (min) Tensile Strength (kPa) Compressive Strength (kPa)
Example 1 30 14 6
Example 2 45 18 11
Example 3 32 15 7
Comparative example 1 3 65 40
Comparative example 2 3.5 45 33
According to the embodiments 1-3, the comparative examples 1-2 and the table 1, the hydrogel prepared by the method for preparing the intra-operative stomach filling hydrogel has good mechanical strength and biocompatibility, effectively avoids the phenomenon that the hydrogel is blocked due to premature gelation in the injection process of an injector, is suitable for popularization in the medical field, and has a wide development prospect.
Comparing example 1 with example 3, it can be seen that when calcium sulfate is used as an adjuvant in example 3, calcium sulfate is slightly soluble, so that calcium sulfate powder is only required to be slowly added to deionized water until the calcium sulfate powder is no longer dissolved, and after the precipitate is stable, the supernatant can be directly taken as an auxiliary liquid, and the gelling property and time are similar to those of example 1, but due to the fixed solubility, the prepared auxiliary liquid is dissolved at 18-40 ℃, and 0.26 ± 0.005g of calcium sulfate is contained in 100g of deionized water, so that on the premise of keeping various advantages of example 1, the preparation process is greatly simplified, the time is saved, and the production cost is reduced.
Wherein, the examples 1 and 3 obtain the best performance index under the factors of the best preparation raw material proportion, preparation process and the like.

Claims (10)

1. A preparation method of intraoperative gastric filling hydrogel is characterized by comprising the following steps: the steps at least comprise the following steps: (1) preparing an organic acid salt solution; (2) preparing an adjuvant solution; (3) mixing the components in proportion.
2. The method of preparing an intraoperative gastric filling hydrogel of claim 1, wherein: the organic acid salt is at least one of sodium alginate, calcium alginate, potassium alginate and lithium alginate.
3. The method of preparing an intraoperative gastric filling hydrogel of claim 2, wherein: the preparation of the organic acid salt comprises the following specific operations: adding the organic acid salt into deionized water, and violently stirring for 2-4 hours until the organic acid salt is completely dissolved to obtain an organic acid salt solution.
4. The method for preparing an intraoperative gastric filling hydrogel according to claim 3, wherein: the mass ratio of the organic acid salt to the deionized water is 0.1-1: 80-120 parts.
5. The method for preparing an intraoperative gastric filling hydrogel according to claim 4, wherein: the adjuvant is calcium gluconate and/or calcium sulfate.
6. The method for preparing an intraoperative gastric filling hydrogel according to claim 5, wherein: the preparation of the adjuvant solution is specifically carried out by: and adding the auxiliary agent into deionized water, and stirring vigorously for 2-4 hours until the auxiliary agent is completely dissolved to obtain an auxiliary agent solution.
7. The method of preparing an intraoperative gastric filling hydrogel of claim 6, wherein: the mass ratio of the auxiliary agent to the deionized water is 0.1-0.5: 80-120 parts.
8. The method of preparing an intraoperative gastric filling hydrogel of claim 7, wherein: the specific operation of the mixture preparation is as follows: and respectively sucking the organic acid salt solution and the adjuvant solution by using different injectors, simultaneously injecting the organic acid salt solution and the adjuvant solution into a mold according to a fixed volume ratio, quickly and uniformly mixing, and standing for 1-60 minutes to obtain the hydrogel.
9. The method of preparing an intraoperative gastric filling hydrogel of claim 8, wherein: the volume ratio of the organic acid salt solution to the adjuvant solution is 1-10: 1-10.
10. Use of a hydrogel prepared by the method of preparation of an intra-operative gastric filling hydrogel according to any one of claims 1 to 9, wherein: including the use of the hydrogel for filling in gastric surgery.
CN202210238443.9A 2022-03-11 2022-03-11 Preparation method and application of intraoperative gastric filling hydrogel Pending CN114409932A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102532564A (en) * 2012-01-16 2012-07-04 孙珊 Hydrogel and preparation method thereof
CN107115562A (en) * 2017-04-11 2017-09-01 上海交通大学 A kind of injection aquagel and its preparation and application for myocardial repair
CN114015073A (en) * 2017-11-24 2022-02-08 杭州德柯医疗科技有限公司 Hydrogel for injecting organisms and application thereof
WO2022028244A1 (en) * 2020-08-04 2022-02-10 宁波迪创医疗科技有限公司 Tissue filling material, preparation method therefor, tissue engineering scaffold and use

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102532564A (en) * 2012-01-16 2012-07-04 孙珊 Hydrogel and preparation method thereof
CN107115562A (en) * 2017-04-11 2017-09-01 上海交通大学 A kind of injection aquagel and its preparation and application for myocardial repair
CN114015073A (en) * 2017-11-24 2022-02-08 杭州德柯医疗科技有限公司 Hydrogel for injecting organisms and application thereof
WO2022028244A1 (en) * 2020-08-04 2022-02-10 宁波迪创医疗科技有限公司 Tissue filling material, preparation method therefor, tissue engineering scaffold and use

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