Hydrogel lithotripsy method for urinary surgery holmium laser lithotripsy
By preparing and injecting urological holmium laser gravel hydrogel, magnetic hydrogel adsorbs stones, the problem of difficult removal of small gravel chips after holmium laser gravel is solved, achieving efficient and safe stone removal effect.
Patent Information
- Application Number
- CN202510582545.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-07
- Publication Date
- 2025-08-05
AI Technical Summary
In the prior art, smaller gravel crumbs and powder after holmium laser gravel are difficult to grab through the stone net basket, resulting in the patient having to drink a lot of water and exercise to discharge, and the residual powder may form stones again, causing pain to the patient.
The hydrogel stone extraction method is adopted to prepare N-succinyl chitosan, oxidized hyaluronic acid and magnetic hydrogel, and the hydrogel is injected with a soft ureter and adsorbed the stone with a magnet rod. Combining biocompatibility and biodegradability, the efficient removal of gravel is achieved.
It improves the efficiency of removing gravel chips and powders, reduces the patient's pain and the risk of stone regeneration, and the hydrogel degrades rapidly in the body, avoiding long-term residues.
Smart Images
Figure CN120420265A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of urology, in particular to a hydrogel lithotripsy method for holmium laser lithotripsy in urology. Background Art
[0002] In clinical practice, holmium lasers can be used to pulverize urinary stones (including kidney stones, ureteral stones, and bladder stones) to treat diseases and alleviate patient pain. However, during the lithotripsy process, the stones are broken into fragments and powder. While some larger fragments can be captured using a stone retrieval basket, smaller fragments and powder cannot be removed, especially for stones in the kidneys.
[0003] These smaller stone fragments and powders can only be excreted by drinking plenty of water to promote urination and assisting with appropriate exercise. This process sometimes causes renal colic. In addition, the stone powders that continue to accumulate in the urinary system may continue to form larger stones, causing pain to the patient. Summary of the Invention
[0004] The purpose of the present invention is to provide a hydrogel stone removal method for holmium laser lithotripsy in urology to solve the problems raised in the above background technology.
[0005] To achieve the above-mentioned object, the present invention provides the following technical solution: a hydrogel lithotripsy method for urological surgery using holmium laser lithotripsy, comprising the following steps:
[0006] S1: Preparation of hydrogel;
[0007] A1: Preparation of N-succinyl chitosan: Succinic anhydride and chitosan were weighed and dissolved in dimethyl sulfoxide. The mixture was heated and stirred, and then filtered to obtain a precipitate. The precipitate was then dispersed in water, and the pH of the solution was adjusted to 10-12 to form a yellow viscous solution. Acetone was added to form a precipitate. The precipitate was filtered and washed three times with acetone. The remaining acetone was dried in a vacuum oven to remove the remaining acetone, and then dissolved in water and freeze-dried to obtain N-succinyl chitosan.
[0008] A2: Preparation of oxidized hyaluronic acid: Weigh hyaluronic acid and dissolve it in deionized water. Then add sodium periodate solution and stir in the dark. Then add ethylene glycol and stir to quench the unreacted sodium periodate. Finally, dialyze the solution and lyophilize to obtain oxidized hyaluronic acid.
[0009] A3: Preparation of magnetic hydrogel: Weigh oxidized hyaluronic acid and dissolve it in deionized water, add ferrosoferric oxide nanoparticles, weigh N-succinyl chitosan and dissolve it in water, take a certain volume of the two solutions and mix and stir to obtain a magnetic hydrogel.
[0010] S2: Injection of magnetic hydrogel: During or after lithotripsy, hydrogel is injected through the working channel of the ureteroscope. The injection amount of magnetic hydrogel is adjusted according to the size and location of the stone, generally enough to fully wrap the stone.
[0011] S3: Stone removal: For larger stones, a stone removal basket has been used to remove the stones from the body in advance. Smaller stones can be adsorbed outside the body using a magnet rod with the assistance of hydrogel.
[0012] Preferably, in the step A1 of preparing N-succinyl chitosan, the heating and stirring temperature is 30-80° C. and the time is 2-5 h.
[0013] Preferably, in the step A1 of preparing N-succinyl chitosan, the mass-to-volume ratio of chitosan, succinic anhydride and dimethyl sulfoxide is 0.5-2 g:0.5-2 g:10-40 ml, and the concentration of sodium hydroxide is 1-10 mol / L.
[0014] Preferably, in the step A2 of preparing oxidized hyaluronic acid, the stirring time is 2-8 hours and the dialysis time is 2-4 days.
[0015] Preferably, in the A2 step of preparing oxidized hyaluronic acid, the mass and volume ratio of hyaluronic acid, deionized water, sodium periodate solution, and ethylene glycol is 0.5-2 g: 50-200 ml: 1-10 ml: 0.5-2 ml, the concentration of sodium periodate solution is 10-100 mg / ml, and the molecular weight cutoff of the dialysis bag used in dialysis is 8000-14000 Da.
[0016] Preferably, in the A3 step of preparing the magnetic hydrogel, the volume and mass ratio of the oxidized hyaluronic acid solution, N-succinyl chitosan solution, and ferrosoferric oxide nanoparticles is 10-50 μL: 10-50 μL: 10-100 mg, and the concentration ratio of the oxidized hyaluronic acid solution and N-succinyl chitosan is 10-80 mg / mL: 10-80 mg / mL.
[0017] Compared with the prior art, the present invention has the following beneficial effects:
[0018] 1. Hydrogels are mainly synthesized using hyaluronic acid (HA) and chitosan (CS) as raw materials. Hyaluronic acid (HA) has excellent biocompatibility and biodegradability, and also contains rich functional groups such as hydroxyl, carboxyl and acetyl groups. These groups provide multiple possibilities for chemical modification.
[0019] 2. Chitosan (CS) is a natural polysaccharide obtained from the alkaline hydrolysis of chitin. It mainly comes from the exoskeletons of crustaceans and insects and the cell walls of fungi. It is one of the most abundant natural amino polysaccharides in nature. CS has a series of unique biological properties, including antibacterial properties, biocompatibility, biodegradability, hemostasis, and the ability to promote cell adhesion, proliferation and differentiation.
[0020] 3. Oxidized hyaluronic acid (OHA) can be prepared by oxidizing the hydroxyl groups on hyaluronic acid (HA) to aldehyde groups, and then the two are combined to form a new hydrogel, which increases its convenience in the field of holmium laser lithotripsy in urology. At the same time, its higher water solubility also enables it to be better degraded and excreted from the human body through urine after surgery. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 1H NMR spectra of hyaluronic acid (HA), chitosan (CS), oxidized hyaluronic acid (OHA), and succinic anhydride-modified chitosan (NSC) in Example 1 of the present invention.
[0022] Figure 2 This is the size distribution curve of ferroferric oxide nanoparticles in Example 1 of the present invention.
[0023] Figure 3 This is a curve showing the change in viscosity of the oxidized hyaluronic acid / succinic anhydride modified chitosan hydrogel in Example 1 of the present invention over time in a calcium ion environment under constant temperature and constant shear rate conditions (simulating the change in viscosity of the hydrogel after contact with the stone during stone removal).
[0024] Figure 4 This is a scanning electron microscope image of the oxidized hyaluronic acid / succinic anhydride modified chitosan hydrogel in Example 1 of the present invention.
[0025] Figure 5 This is the degradation curve of the oxidized hyaluronic acid / succinic anhydride modified chitosan hydrogel in Example 1 of the present invention in a calcium ion environment at a constant temperature (simulating the degradation of the hydrogel after contact with the stone during the stone removal process).
[0026] Figure 6 This is a diagram showing the biocompatibility experiment of the oxidized hyaluronic acid / succinic anhydride modified chitosan hydrogel in Example 1 of the present invention. DETAILED DESCRIPTION
[0027] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.
[0028] Example 1
[0029] See also Figures 1-6 The present invention provides a technical solution: a hydrogel stone removal method for holmium laser lithotripsy in urology, comprising the following steps:
[0030] S1: Preparation of hydrogel;
[0031] A1: Preparation of N-succinyl chitosan: 1 g of chitosan was dissolved in 20 mL of DMSO, 1 g of succinic anhydride was added, and the mixture was stirred at 500 rpm for 4 hours at 60 ° C. The precipitate was collected by filtration and dispersed in 50 mL of water. During the stirring process, 5 mol / L NaOH solution was added dropwise to adjust the pH to 10-12 to form a yellow viscous solution. Subsequently, acetone was added to precipitate the solution, which was collected by filtration and washed three times with acetone. The resulting precipitate was placed in a vacuum oven and dried for one day to remove the remaining acetone. Finally, the product was dissolved in water and freeze-dried to obtain N-succinyl chitosan.
[0032] A2: Preparation of oxidized hyaluronic acid: 1 g of hyaluronic acid was dissolved in 100 mL of deionized water and stirred at room temperature for 5 hours to ensure complete dissolution to obtain a HA solution with a concentration of 10 mg / mL. Subsequently, 10 mL of 5 mol / L sodium periodate solution was added and stirred for 4 hours under light-proof conditions. Next, 2 mL of ethylene glycol was added and stirred for 1 hour to quench the unreacted sodium periodate. Finally, the solution was dialyzed for 3 days using a dialysis bag with a molecular weight of 8000-14000 Da to remove small molecule impurities, and then the product oxidized hyaluronic acid was obtained by freeze-drying.
[0033] A3: Preparation of magnetic hydrogel: Dissolve 0.6 g of oxidized hyaluronic acid and N-succinyl chitosan in 10 ml of deionized water to prepare a 60 mg / ml solution. Disperse 0.25, 0.5, and 0.75 g of ferroferric oxide nanoparticles into the oxidized hyaluronic acid solution. Mix 1 ml of the oxidized hyaluronic acid solution containing ferroferric oxide with 1 ml of the N-succinyl chitosan solution and stir to prepare the oxidized hyaluronic acid / N-succinyl chitosan hydrogel, i.e., the magnetic hydrogel.
[0034] In order to further simulate the viscosity and degradation changes of hydrogel after contact with stones during stone removal. Figure 3 and Figure 5 In some experiments, a certain amount of CaCl2 was added to artificially create a calcium ion environment. The calcium ion concentration was 1-120 mg / mL and the stirring time was 0-5 min.
[0035] S2: Injection of magnetic hydrogel: During or after lithotripsy, hydrogel is injected through the working channel of the ureteroscope. The injection amount of magnetic hydrogel is adjusted according to the size and location of the stone, generally enough to fully wrap the stone.
[0036] S3: Stone removal: For larger stones, a stone removal basket has been used to remove the stones from the body in advance. Smaller stones can be adsorbed outside the body using a magnet rod with the assistance of hydrogel.
[0037] Implementation results:
[0038] like Figure 1 Shown are the hydrogen nuclear magnetic resonance spectra of hyaluronic acid, chitosan, oxidized hyaluronic acid, and succinic anhydride-modified chitosan prepared in Example 1. The spectrum of oxidized hyaluronic acid shows three new characteristic peaks in the range of 4.9-5.1 ppm, which correspond to aldehyde groups; N-succinyl chitosan shows two new characteristic peaks at 2.40–2.49 ppm, which are attributed to the hydrogen atoms on the -NHCOCH2- and -CH2COO- methylene groups, respectively.
[0039] Figure 2 This is the size distribution curve of the ferrosoferric oxide nanoparticles in Example 1; the size of most of the ferrosoferric oxide nanoparticles is around 150 nm.
[0040] Figure 3 The viscosity of the oxidized hyaluronic acid / succinic anhydride modified chitosan hydrogel in Example 1 changes with time in a calcium ion environment under constant temperature and constant shear rate conditions (simulating the viscosity change of the hydrogel after contact with the stone during stone removal); the hydrogel samples containing Fe3O4NPs all exhibited a high viscosity, greater than 800Pa·s, while the viscosity of the hydrogel without Fe3O4NPs was only 500Pa·s. This shows that the addition of Fe3O4NPs significantly increased the viscosity of the hydrogel, and the viscosity showed a gradual increase with increasing Fe3O4NPs content. In addition, throughout the test time, the viscosity of all hydrogel samples containing Fe3O4NPs remained stable and did not show a significant decrease; in contrast, the viscosity of the blank hydrogel without Fe3O4NPs gradually decreased over time.
[0041] Figure 4This is a scanning electron microscope image of the oxidized hyaluronic acid / succinic anhydride modified chitosan hydrogel in Example 1. The image shows that the cross-section of the hydrogel presents a morphology combining porous and fibrous structures. The pore size of the NSC-OHA hydrogel is about 150 μm.
[0042] Figure 5 This is the degradation curve of the oxidized hyaluronic acid / succinic anhydride-modified chitosan hydrogel in Example 1 in a calcium ion environment at a constant temperature (simulating the degradation of the hydrogel after contact with stones during stone removal). The hydrogel completely degraded in approximately three days in both phosphate-buffered saline (PBS) solution at pH 7.4 and ultrapure water; in ultrapure water at pH 5.6, the hydrogel completely degraded by the fifth day. Hydrogels that can degrade rapidly within a few days are important for the recovery of kidney stone fragments in vivo.
[0043] Figure 6 This is a graph showing the biocompatibility of the oxidized hyaluronic acid / succinic anhydride modified chitosan hydrogels in Example 1. It can be seen from the graph that several NSC-OHA hydrogels showed no significant cytotoxicity to 5637 cells, which is very important for the use of hydrogels in biomedical applications.
[0044] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.
Claims
1. A hydrogel lithotripsy method for urological holmium laser lithotripsy, characterized by: The following steps are involved: S1: Preparation of hydrogel; A1: Preparation of N-succinyl chitosan: Succinic anhydride and chitosan were weighed and dissolved in dimethyl sulfoxide. The mixture was heated and stirred, and then filtered to obtain a precipitate. The precipitate was then dispersed in water, and the pH of the solution was adjusted to 10-12 to form a yellow viscous solution. Acetone was added to form a precipitate. The precipitate was filtered and washed three times with acetone. The precipitate was dried in a vacuum oven to remove the remaining acetone, and then dissolved in water and freeze-dried to obtain N-succinyl chitosan. A2: Preparation of oxidized hyaluronic acid: Hyaluronic acid was weighed and dissolved in deionized water, followed by addition of sodium periodate solution. The mixture was stirred in the dark, followed by addition of ethylene glycol and stirring to quench any unreacted sodium periodate. The solution was then dialyzed and lyophilized to obtain oxidized hyaluronic acid. A3: Preparation of magnetic hydrogel: Weigh oxidized hyaluronic acid and dissolve it in deionized water. Add ferrosoferric oxide nanoparticles. Weigh N-succinyl chitosan and dissolve it in water. Take a certain volume of the two solutions and mix them to obtain a magnetic hydrogel. S2: Injection of magnetic hydrogel: During or after lithotripsy, hydrogel is injected through the working channel of the ureteroscope. The amount of magnetic hydrogel injected is adjusted according to the size and location of the stone, generally to fully encapsulate the stone. S3: Stone removal: For larger stones, a stone removal basket has been used to remove the stones from the body in advance. Smaller stones can be adsorbed outside the body using a magnet rod with the assistance of hydrogel.
2. The hydrogel lithotripsy method for urological holmium laser lithotripsy according to claim 1, characterized in that: In the step A1 of preparing N-succinyl chitosan, the heating and stirring temperature is 30-80° C. and the time is 2-5 hours.
3. The hydrogel lithotripsy method for urological holmium laser lithotripsy according to claim 2, characterized in that: In the step A1 of preparing N-succinyl chitosan, the mass and volume ratio of chitosan, succinic anhydride and dimethyl sulfoxide is 0.5-2g:0.5-2g:10-40ml, and the concentration of sodium hydroxide is 1-10mol / L.
4. The hydrogel lithotripsy method for urological holmium laser lithotripsy according to claim 3, characterized in that: In the A2 step of preparing oxidized hyaluronic acid, the stirring time is 2-8 hours, and the dialysis time is 2-4 days.
5. The hydrogel lithotripsy method for urological holmium laser lithotripsy according to claim 4, characterized in that: In the A2 step of preparing oxidized hyaluronic acid, the mass and volume ratio of hyaluronic acid, deionized water, sodium periodate solution, and ethylene glycol is 0.5-2 g: 50-200 ml: 1-10 ml: 0.5-2 ml, the concentration of the sodium periodate solution is 10-100 mg / ml, and the molecular weight cutoff of the dialysis bag used in dialysis is 8000-14000 Da.
6. The hydrogel lithotripsy method for urological holmium laser lithotripsy according to claim 5, characterized in that: The volume and mass ratio of the oxidized hyaluronic acid solution, N-succinyl chitosan solution, and ferrosoferric oxide nanoparticles in the A3 step of preparing the magnetic hydrogel is 10-50 μL:10-50 μL:10-100 mg, and the concentration ratio of the oxidized hyaluronic acid solution and N-succinyl chitosan is 10-80 mg / mL:10-80 mg / mL.