CN114522277B

CN114522277B - Design synthesis of in-situ gel and application of in-situ gel in medicament for removing calculus and fragments

Info

Publication number: CN114522277B
Application number: CN202210029164.1A
Authority: CN
Inventors: 赖德辉; 吴丁财; 何汶懿; 江先汉; 卞军; 郭耀川; 黄榕康; 吴淑仪; 靳林; 何永忠
Original assignee: Sun Yat Sen University; Fifth Affiliated Hospital of Guangzhou Medical University
Current assignee: Sun Yat Sen University; Fifth Affiliated Hospital of Guangzhou Medical University
Priority date: 2022-01-11
Filing date: 2022-01-11
Publication date: 2022-11-18
Anticipated expiration: 2042-01-11
Also published as: CN114522277A

Abstract

The invention discloses a designed synthesis of in-situ gel and application thereof in a medicament for removing stones and fragments, belonging to the technical field of medical material methods; the in-situ gel provided by the technical scheme of the invention can form ultra-fast gel in a neutral environment in vivo and specifically and tightly wrap the calculus and fragments thereof; the technical scheme of the invention is applied to removing the calculus and the fragments thereof, has the advantages of good biocompatibility, degradability, strong operability, specific coating of the calculus and the fragments thereof and the like, can effectively improve the operation efficiency and the clearance rate of the calculus and the fragments thereof, reduce the operation times and reduce the recurrence rate of the calculus, and has application prospect in the operation in the cavity of the urinary system such as a ureteroscope and the like.

Description

Design synthesis of in-situ gel and application of in-situ gel in medicament for removing calculus and fragments

Technical Field

The invention belongs to the field of medical material methods for urology surgery, and particularly relates to design synthesis of an in-situ gel and application of the in-situ gel in a medicament for removing stones and fragments.

Background

At present, retrograde intra-renal surgery (RIRS) based on a flexible-URS (flexible-URS) is a safer and minimally invasive method for treating intrarenal calculi. The RIRS operation is a procedure in which a large stone is broken into extractable fragments by means of laser lithotripsy, and the broken stone of a certain size is taken out of the kidney through a ureteral sheath (UAS) by means of a stone basket. Despite long-term optimization of laser systems, devices and surgical methods, laser lithotripsy inevitably results in the production of large quantities of tiny, unsmokable stone fragments that remain in the urinary system. The residual stone fragments can cause renal colic in the stone removing process, even the formation of ureter stone street, and cause the damage of renal function; in addition, the patient who naturally removes the calculus needs to keep the inner stent tube for a long time, so that the infection and the discomfort related to the stent tube are increased, and the life quality of the patient is seriously reduced. Finally, residual calculus may serve as a focus for secondary calculus formation, a risk factor for recurrence of calculus, and the likelihood of the patient needing re-surgery is high.

The current method for removing residual tiny calculus fragments in kidney is mainly a natural calculus removal method. In order to increase the removal rate of calculus, some experts propose the idea of forming and removing the adhesion body together with calculus during the operation by injecting curable liquid such as patient's own blood and adhesive polysaccharide solution, etc., but such techniques are not well popularized due to the problems of unclear field of vision, long curing time, complicated material preparation and residual in vivo risk. At present, in the existing patents (such as CN 105491966A), an acidic solution containing iron ions, calcium ions and polysaccharide is combined with an alginate polysaccharide solution to coat the calculus, but the defects of poor calculus coating effect, strong system acidity, tissue damage and the like still exist, and further popularization and application are influenced.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a designed synthesis method of an in-situ gel and application thereof in a medicament for removing stones and fragments so as to safely, reliably, adaptively and quickly remove the stones and the fragments thereof.

In order to achieve the purpose, the invention adopts the technical scheme that: use of an in situ gel consisting of a dispersion a and a dispersion B, the dispersion a comprising water and a polymer and the dispersion B comprising water and an inorganic salt, in the manufacture of a medicament for the removal of stones and fragments thereof; wherein removing the stones and their fragments comprises the steps of:

(1) Providing a dispersion A and a dispersion B;

(2) Introducing the dispersion system A in the step (1) into an area containing stones and fragments thereof to be removed to obtain an area of stones and fragments thereof wrapped by the dispersion system A;

(3) Introducing the dispersion system B in the step (1) into the area of the calculus and the fragments thereof wrapped by the dispersion system A in the step (2), wherein the dispersion system B is contacted with the dispersion system A to realize crosslinking to form gel, so as to obtain the calculus and the fragments thereof tightly wrapped by the crosslinked gel;

(4) Stones and their fragments tightly encapsulated by the crosslinked gel are removed.

The application of the in-situ gel provided by the technical scheme of the invention in preparing the medicine for removing the calculus and the fragments thereof, wherein the in-situ gel can form the gel in an ultra-fast manner in a neutral environment in vivo and specifically and tightly wraps the calculus and the fragments thereof; the technical scheme of the invention is applied to removing the calculus and the fragments thereof, has the advantages of good biocompatibility, degradability, strong operability, specific coating of the calculus and the fragments thereof and the like, can effectively improve the operation efficiency and the clearance rate of the calculus and the fragments thereof, reduce the operation times, reduce the recurrence rate of the calculus and has the potential of being applied to the operation in the cavity of the urinary system such as a ureteroscope and the like.

As a preferred embodiment of the use according to the invention, the step (2) further comprises introducing a stone-setting basket into the region of stones and fragments thereof enclosed by the dispersion system a or into the region of stones and fragments thereof enclosed tightly by the cross-linked gel after the region of stones and fragments thereof enclosed tightly by the dispersion system a is obtained or after the step (3) further comprises introducing a stone-setting basket into the region of stones and fragments thereof enclosed tightly by the dispersion system a or into the region of stones and fragments thereof enclosed tightly by the cross-linked gel.

As a preferred embodiment of the use of the present invention, the step (2) further comprises introducing a stone-covering basket into the region of the stone and its fragments surrounded by the dispersion system a after the region of the stone and its fragments surrounded by the dispersion system a is obtained.

The introduction of the stone-covered basket can prevent the excessive flow of the dispersion system A in the body in the early stage; and the gel wrapping the calculus and the fragments thereof can be prevented from being cut by the stone-covering basket to influence the taking-out after the dispersion system B is introduced.

As a preferred embodiment of the use according to the invention, the dispersion a also comprises a colorant.

The colorant is introduced into the dispersion system A, so that the gel wrapping the calculus can be effectively tracked, and the problem that the hydrogel is difficult to position in the introduction and removal processes is effectively solved.

As a preferred embodiment of the use according to the present invention, the colorant comprises any one of methylene blue, indigo carmine, lac red, phenol red, congo red and crystal violet.

As a preferred embodiment of the use of the present invention, the colorant is any one of methylene blue, beet red and shellac red.

The colorant of the above kind is selected, on one hand, the colorant of the above kind has good water solubility and can be well dissolved in the dispersion system A and then introduced into the calculus area, and on the other hand, the colorant of the above kind has mild properties and no strong acid or strong alkalinity, so that the introduced colorant can be prevented from causing irritation to a patient, and meanwhile, the colorant of the above kind is simple to obtain.

As a preferred embodiment of the use according to the invention, the concentration of the polymer in the dispersion A is between 1.0% and 2.0% and the concentration of the colorant in the dispersion A is between 0.0001% and 0.01%.

In a preferred embodiment of the use of the present invention, the concentration of the polymer in the dispersion system a is 2.0% and the concentration of the colorant in the dispersion system a is 0.001%.

As a preferred embodiment of the use according to the invention, the pH of the dispersion A is from 7.0 to 7.4.

Within a certain range, with the increase of the concentration of the polymer in the dispersion system A, the injection pressure when the polymer A is introduced into the area of the urinary system containing the bonds and fragments thereof by injection can be greatly increased, thereby causing the increase of the operation difficulty; meanwhile, in practical application, along with the increase of the concentration of the polymer in the dispersion system A, the strength of the gel formed in the later period is better, and the coating effect is better, so that the operation times required for removing a certain mass of stones and fragments thereof can be reduced; therefore, in consideration of the operational difficulty due to the injection pressure during the introduction and the reduction in the number of operations due to the strength of the gel formed at the later stage and the coating effect, the concentration of the polymer is preferably 1.0% to 2.0%, and particularly preferably 2.0%.

As a preferred embodiment of the use according to the invention, the stones and fragments thereof are stones and fragments thereof of the urinary system.

As a preferred embodiment of the use according to the invention, the polymer is a polysaccharide.

As a preferred embodiment of the use according to the invention, the polymer is a polysaccharide containing sodium carboxylate groups.

In a preferred embodiment of the use of the present invention, the polymer is a polysaccharide obtained by linear polymerization of a monosaccharide acid.

As a preferred embodiment of the use according to the invention, the polymer is alginate polysaccharide.

As a preferred embodiment of the use according to the invention, the polymer is sodium alginate.

Sodium alginate is a linear anionic natural polysaccharide polymerized from beta-D-mannuronic acid (M) and alpha-L-guluronic acid (G) through glycosidic bonds, and is widely applied to the field of biomedicine at present. Sodium alginate is an anionic polymer, the molecular chain of the sodium alginate contains a large number of carboxyl groups, and the sodium alginate can be rapidly ionically crosslinked with ionized calcium ions in a solution to form a hydrogel three-dimensional network framework; calcium-containing calculi (calcium oxalate calculi, calcium phosphate calculi and the like) are the most common types of kidney calculi, a small amount of calcium ions can be ionized on the surfaces of the calculi in aqueous solution, and carboxyl on a sodium alginate molecular chain exists in the form of carboxylate in the aqueous solution and can be chelated with the ionized calcium ions of the calculi to form ionic cross-linked bonds to specifically coat the calculi.

As a preferred embodiment of the use according to the invention, the concentration of the inorganic salt in the dispersion B is between 0.4% and 1.2%.

As a preferred embodiment of the use according to the invention, the concentration of the inorganic salt in the dispersion B is 0.8%.

As a preferred embodiment of the use according to the invention, the pH of the dispersion B is from 6.0 to 7.0.

In the dispersion system a, when the concentration of the polymer is constant, the increase of the concentration of the inorganic salt in the dispersion system B within a certain range can significantly increase the strength of the gel formed at the later stage, but the change of the clearance rate is not significant after the increase of the concentration to a certain value, and therefore, the concentration of the inorganic salt is preferably 0.8% in the present invention.

As a preferred embodiment of the use according to the invention, the cation of the inorganic salt is a divalent or polyvalent cation.

As a preferred embodiment of the use according to the invention, the cation of the inorganic salt is calcium.

As a preferred embodiment of the use according to the invention, the inorganic salt is calcium chloride.

Calcium chloride is preferably used as the inorganic salt in the dispersion system B, on one hand, the calcium chloride solution is neutral and does not cause damage to tissues and organs; on the other hand, a small amount of calcium ions ionized by the calculus in the water environment can be quickly crosslinked with polymer sodium alginate in the introduced dispersion system A to form gel with certain mechanical property, so that the introduced dispersion system A can initially wrap the calculus and fragments thereof, at the moment, the dispersion system B is introduced, a large amount of calcium ions in the dispersion system B can be further quickly crosslinked with the sodium alginate, the gel formed in the early stage is reinforced and strengthened, and the specific adhesion and the wrapping of the calculus and the fragments thereof are finally realized, so that the calculus can be taken out from the urinary system by common surgical instruments such as a stone basket and the like.

As a preferred embodiment of the use according to the invention, in said step (1), the volume of dispersion A introduced is between 0.1 and 2.0mL.

The volume of dispersion a introduced into the region of urinary stones and fragments thereof, if too small, will result in ineffective coating of the stones and fragments thereof, and if too large, will result in too much dispersion a not being removed from the introduction portion, and therefore, the present invention preferably introduces a volume of dispersion a of 0.1-2.0mL.

As a preferred embodiment of the use according to the invention, in step (3), the ratio of the volume of dispersion B introduced to the volume of dispersion a introduced in step (1) is 10.

When the volume ratio of the introduced dispersion B to the volume of the dispersion a introduced in step (1) is 10.

As a preferred embodiment of the use of the invention, in the step (3), after the dispersion B is introduced, the stone-covered basket is tightly covered after 5-60 seconds.

Compared with the prior art, the invention has the following beneficial effects:

firstly, the method comprises the following steps: the application of the in-situ gel in preparing the medicine for removing the calculus and the fragments thereof, which is provided by the technical scheme of the invention, has the advantages of simplicity, good biocompatibility, degradability and low cost, and can be quickly and specifically combined with the calculus and the fragments thereof by utilizing ionic bonds and solidified, so that the in-situ gel is convenient to take out at the later stage;

secondly, the method comprises the following steps: the technical scheme of the invention is applied to removing the calculus and the fragments thereof, has the advantages of good biocompatibility, strong operability, specific coating of the calculus and the fragments thereof and the like, can effectively improve the operation efficiency and the clearance rate of the calculus and the fragments thereof, reduce the operation times and the recurrence rate of the calculus, and has the potential of being applied to the operation in the cavity of the urinary system such as a ureter soft lens and the like;

thirdly, the steps of: the technical scheme of the invention is applied to the removal of the calculus and the fragments thereof, does not influence the operation process, does not influence the healing after the operation and does not increase the pain of the patient.

Drawings

FIG. 1 is a graph showing the relationship between sodium alginate and injection pressure in effect example 1;

FIG. 2 is a graph showing the relationship between the sodium alginate concentration and the calcium chloride concentration and the clearance of hydrogel fragments in effect example 2;

FIG. 3 is a graph showing the relationship between the sodium alginate concentration and the number of operations required to remove 200mg of kidney stone fragments having an average particle size of 2mm in effect example 3;

FIG. 4 is a graph showing the relationship between the concentration of sodium alginate and the volume of a solution required for removing 200mg of kidney stone fragments having an average particle size of 2mm in effect example 3;

FIG. 5 is a Fourier transform infrared spectrum of the dispersion system A, kidney stone, sodium alginate in-situ gel and kidney stone coated in-situ gel prepared in example 1 detected by attenuated total reflection Fourier infrared spectrum in effect example 4;

FIG. 6 is a surface topography of sodium alginate in-situ gel prepared in example 1 observed by a thermal field emission scanning electron microscope in effect example 5;

FIG. 7 is a surface topography of the sodium alginate in-situ gel coated with kidney stones prepared in example 1, as observed by thermal field emission scanning electron microscopy in effect example 5;

FIG. 8 is an element map of sodium alginate in-situ gel obtained in example 1 observed by a thermal field emission scanning electron microscope in effect example 6;

FIG. 9 is an element map of effect example 6, which is obtained by observing the sodium alginate in-situ gel coated with kidney stones prepared in example 1 by using a thermal field emission scanning electron microscope;

FIG. 10 is a graph showing the results of the procedure of Effect example 7 for removing a mass of kidney stone fragments in the manner of comparative example 1;

FIG. 11 is a graph showing the results of effect example 8 in which the gel prepared in example 1 was evaluated for cell compatibility by the CCK8 method;

FIG. 12 is a detailed operational view showing the complete removal of 100mg of kidney stone fragments in a simulated kidney according to example 1 of the present invention.

Detailed Description

To better illustrate the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to specific examples.

Example 1

The invention relates to a method for removing stones and fragments thereof from a body containing the stones and fragments thereof to be removed, comprising the following steps:

(1) Adding sodium alginate and methylene blue into deionized water, mixing and stirring to prepare a dispersion system A with the sodium alginate concentration of 2.0% and the methylene blue concentration of 0.001%, wherein the pH value of the dispersion system A is about 7.0; dissolving anhydrous calcium chloride in deionized water to prepare a dispersion system B with the calcium chloride concentration of 0.8%, wherein the pH value of the dispersion system B is about 6.4;

(2) Simulating that the kidney is continuously injected with physiological saline at the flow rate of 2.0 mL/min;

(3) Injecting 0.1mL of the dispersion A into a simulated kidney region containing kidney stone fragments to be removed through a No. 5 tube;

(4) Introducing a stone basket into the region of the stone surrounded by dispersion a;

(5) Injecting 1.0mL of dispersion B through a No. 5 tube to the side of the area in the step (3), crosslinking and fixing the dispersion B to coat the stone fragments, and waiting for 30 seconds;

(6) Firmly sleeving the gel by using a stone sleeving basket, and removing the gel coated with the stone fragments from the simulated kidney through a ureteral sheath;

the specific operation steps are shown in fig. 12.

Example 2

(1) Adding sodium alginate and methylene blue into deionized water, mixing and stirring to prepare a dispersion system A with the sodium alginate concentration of 1.0% and the methylene blue concentration of 0.001%, wherein the pH value of the dispersion system A is about 7.0; dissolving anhydrous calcium chloride in deionized water to prepare a dispersion system B with the calcium chloride concentration of 0.8%, wherein the pH value of the dispersion system B is about 6.4;

(5) Injecting 1.0mL of the dispersion B into the area of the step (3) through a No. 5 tube, crosslinking and fixing the dispersion B to coat the stone fragments, and waiting for 30 seconds;

(6) The gel was secured with a stone-covered basket and the stone-debris coated gel was removed from the simulated kidney through the ureteral sheath.

Example 3

The removal of stones and fragments thereof from a body containing the stones and fragments thereof to be removed according to the present invention comprises the steps of:

(1) Adding sodium alginate and methylene blue into deionized water, mixing and stirring to prepare a dispersion system A with the sodium alginate concentration of 1.5% and the methylene blue concentration of 0.001%, wherein the pH value of the dispersion system A is about 7.0; dissolving anhydrous calcium chloride in deionized water to prepare a dispersion system B with the calcium chloride concentration of 0.8%, wherein the pH value of the dispersion system B is about 6.4;

Example 4

(1) Adding sodium alginate and methylene blue into deionized water, mixing and stirring to prepare a dispersion system A with the sodium alginate concentration of 2.0% and the methylene blue concentration of 0.001%, wherein the pH value of the dispersion system A is about 7.0; dissolving anhydrous calcium chloride in deionized water to prepare a dispersion system B with the calcium chloride concentration of 0.4%, wherein the pH value of the dispersion system B is about 6.1;

(3) Injecting 0.1mL of dispersion A into a simulated kidney region containing kidney stone fragments to be removed via a No. 5 tube;

Example 5

(1) Adding sodium alginate and methylene blue into deionized water, mixing and stirring to prepare a dispersion system A with the sodium alginate concentration of 2.0% and the methylene blue concentration of 0.001%, wherein the pH value of the dispersion system A is about 7.0; dissolving anhydrous calcium chloride in deionized water to prepare a dispersion system B with the calcium chloride concentration of 1.2%, wherein the pH value of the dispersion system A is about 6.5;

Comparative example 1

The removal of stones and fragments thereof from a body containing the stones and fragments thereof to be removed in comparison to the prior literature comprises the following steps:

(1) Adding sodium alginate and methylene blue into deionized water, mixing and stirring to prepare a dispersion system C with the sodium alginate concentration of 1.0% and the methylene blue concentration of 0.0005%; dissolving ferric chloride in deionized water to prepare a dispersion system D with the concentration of the ferric chloride being 1 mol/L; dissolving chitosan in deionized water to prepare a dispersion system E with the concentration of the chitosan being 0.32% and the pH value being about 6.0; dissolving oxalic acid in deionized water to prepare a dispersion system F with the concentration of oxalic acid being 1 mol/L;

(2) Mixing and uniformly stirring 1.4mL of a dispersion system D, 8.6mL of a dispersion system E and 13 drops of a dispersion system F to obtain a dispersion system G, wherein the pH value of the dispersion system G is about 1.0;

(3) Injecting 10mL of dispersion G through tube No. 5 into the area containing the kidney stone fragments to be removed;

(4) Injecting 10mL of dispersion C through tube No. 5 into the area containing the kidney stone fragments to be removed, waiting for 60 seconds;

(4) The stone-covered basket is introduced into the area of the stone which has been covered with dispersion C, the gel is secured with the basket, and the gel covering the stone fragments is removed from the simulated kidney by means of the ureteral sheath.

Effect example 1

This effect example measured the injection pressure of the dispersion system a of examples 1 to 3 at different concentration values of sodium alginate during the simulated surgery, and the results are shown in fig. 1. As can be seen from fig. 1, the injection pressure increased greatly with increasing concentration of sodium alginate in the dispersion a.

Effect example 2

This effect example examines the ratio of different concentration values of sodium alginate in the dispersion system a and different concentration values of calcium chloride in the dispersion system B in examples 1 to 5 that can be taken out of hydrogel by the rock-jacketed basket during the simulated surgery through the continuous injection and flushing of physiological saline with a flow rate of 0.2mL/s, and the test results are shown in fig. 2, wherein calcium chloride in the dispersion system B in fig. 2 is represented by Ca and sodium alginate in the dispersion system a is represented by SA, and it can be seen that as the concentration of sodium alginate in the dispersion system a and the concentration of calcium chloride in the dispersion system B increase continuously, the gel can maintain its structure under the continuous flushing of physiological saline, is not flushed by water, and can be taken out of the rock-jacketed basket completely from the simulated conditions.

Effect example 3

Examination of various concentration values of sodium alginate in Dispersion A in examples 1-3 the number of operations and volume of Dispersion A required to remove 200mg of kidney stone fragments having an average particle size of 2mm in the manner of the present invention during the course of the simulated surgery are shown in FIGS. 3 and 4. As can be seen from figures 3 and 4, as the concentration of sodium alginate in dispersion a increases, the number of operations required to remove a given amount of kidney stone fragments and the volume of dispersion a solution required both significantly decreases. Thus, increasing the concentration of sodium alginate in dispersion A within an acceptable range of injection pressures can increase the efficiency of the procedure and reduce the duration of the procedure.

Effect example 4

This effect example the chemical properties of the gel prepared in example 1 were examined by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR), and the results are shown in fig. 5; FIG. 5 is a Fourier transform infrared spectrum of an in situ gel system containing sodium alginate, an in situ gel system, a kidney stone, and a coated kidney stone; compared with sodium alginate, no new infrared absorption peak appears in the in-situ gel system, which shows that sodium alginate in the disperse system A and calcium chloride in the disperse system B form gel in an ionic crosslinking mode; meanwhile, compared with the other three, no new infrared absorption peak appears in the in-situ gel system coated with the kidney stone, which shows that the sodium alginate in the disperse system A is combined with the calcium stone in a manner of chelating carboxyl and calcium ions.

Effect example 5

In this effect example, the surface morphology of the gel prepared in example 1 was observed using a thermal field emission scanning electron microscope (QSEM), and the results are shown in fig. 6 and 7; as can be seen from fig. 6 and 7, sodium alginate in dispersion a is capable of interacting with the kidney stone surface; with reference to fig. 5, the sodium alginate in the dispersion system a of the in situ gel system provided by the present invention has the ability to generate specific binding by chelation between carboxyl and calcium ions.

Effect example 6

In this effect example, the element composition and distribution of the gel prepared in example 1 were further observed by using a thermal field emission scanning electron microscope (QSEM), and as a result, as shown in fig. 8 and 9, it can be seen from fig. 8 and 9 that the in situ gel system provided by the present invention can coat kidney stones containing calcium phosphate and magnesium ammonium phosphate.

Effect example 7

The results of this example using the method of comparative example 1 to remove a certain mass of kidney stone fragments are shown in fig. 10. The results show that the dispersion systems G and C are respectively injected into the kidney stone fragment area in the normal saline, and a large amount of sodium alginate solution cannot be effectively coated on the stone fragments to form glue in the process of injecting the dispersion system C, so that the coating effect is poor; in addition, dispersion G, having a pH as low as about 1.0, may be toxic to tissues and cause secondary trauma.

Effect example 8

In this effect example, the cell compatibility of the gel prepared in example 1 was evaluated by the CCK8 method, and the results are shown in fig. 11. The results show that the gel prepared in example 1 has similar CCK8 detection results to the blank cells at 1 day, 3 days and 7 days, has no statistical difference with each other, and increases with the increase of the culture time. It is demonstrated that the gel prepared in example 1 does not cause cytotoxicity.

Finally, it should be noted that the above embodiments are intended to illustrate the technical solutions of the present invention and not to limit the scope of the present invention, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. Use of an in situ gel for the manufacture of a medicament for the removal of stones and fragments thereof, wherein the in situ gel is comprised of a dispersion a comprising water, a polymer and a colorant, and a dispersion B comprising water and an inorganic salt; wherein removing the stones and their fragments comprises the steps of:

(1) Providing a dispersion A having a pH of 7.0 to 7.4 and a dispersion B having a pH of 6.0 to 7.0; in the dispersion system A, the concentration of the polymer is 1.0-2.0%, and the concentration of the colorant is 0.0001-0.01%; in the dispersion system B, the concentration of inorganic salt is 0.4-1.2%; the polymer is sodium alginate; the inorganic salt is calcium chloride;

(3) Introducing the dispersion system B in the step (1) into the area of the calculus and the fragments thereof wrapped by the dispersion system A in the step (2), wherein the dispersion system B is contacted with the dispersion system A to realize crosslinking to form gel, and the calculus and the fragments thereof tightly encapsulated by the crosslinked gel are obtained;

2. The use of claim 1, wherein the step further comprises introducing a littering basket in the region of the stones and fragments thereof encapsulated by the dispersion a or in the region of the stones and fragments thereof encapsulated by the cross-linked gel after the step (2) or after the step (3) of obtaining stones and fragments thereof encapsulated tightly by the cross-linked gel.

3. Use according to claim 1, wherein the stones and fragments thereof are stones of the urinary system and fragments thereof.

4. Use according to claim 1, wherein in step (1) the volume of dispersion a introduced is 0.1-2.0mL.

5. Use according to claim 1, wherein in step (3) the ratio of the volume of dispersion B introduced to the volume of dispersion A introduced in step (1) is 10.