A method for synthesizing gelatin sponge particles

Abstract

The present invention discloses a method for synthesizing gelatin sponge particles, comprising the following steps: preparing a gelatin solution; adding a water-soluble developer and stirring uniformly to obtain a gelatin gel; drying and crushing the solution to obtain a pretreated gelatin powder; placing the pretreated gelatin powder and water in an autoclave and stirring uniformly to obtain a gelatin dispersion; adding a crosslinking agent and a physical foaming agent to the gelatin dispersion to raise the pressure in the autoclave to a first pressure; stopping stirring and releasing the pressure in the autoclave to obtain gelatin sponge particles. The method provided by the present invention first prepares a gelatin gel with a developing function, then dries and crushes the gelatin gel to obtain a pretreated gelatin powder with uniform particles, and then mixes the gelatin powder, the crosslinking agent, and the physical foaming agent in water and crosslinks to form developable gelatin sponge particles with relatively uniform particle size. This method solves the problems of the prior art in which the production of gelatin sponge particles easily causes the destruction of the pore structure and the uncontrollable particle morphology.

Description

Technical Field

[0001] The present invention relates to the technical field of gelatin sponge, in particular to a method for synthesizing gelatin sponge particles. Background Art

[0002] Gelatin sponge particles are generally used in embolization, which is the controlled injection of some artificial embolic materials into the blood vessels supplying the lesion or organ, or into the diseased blood vessels, to cause occlusion and interruption of blood supply, so as to achieve the effects of controlling bleeding, treating vascular lesions and tumors, and eliminating the function of the diseased organ.

[0003] Since gelatin is a natural, non-toxic and harmless high-molecular compound with good biocompatibility, low price and strong water absorption, and gelatin sponge can be degraded and absorbed in the human body in about two weeks, it can restore blood flow after embolism and avoid the pain of blood flow restoration during surgery. Therefore, it is widely used in vascular embolization surgery.

[0004] Most existing gelatin sponge particles are large in size and do not have a developing function. If they are to be made into sponge particles, they need to be crushed, which easily causes the destruction of the pore structure and the particle morphology is uncontrollable. Summary of the Invention

[0005] In order to solve the above technical problems, the present invention provides a method for synthesizing gelatin sponge particles, and the specific technical solution is as follows:

[0006] A method for synthesizing gelatin sponge particles comprises the following steps:

[0007] S1: Place gelatin in water, swell it, and then heat it to dissolve it to prepare a gelatin solution;

[0008] S2: adding a water-soluble developer to the gelatin solution prepared in step S1 and stirring the mixture uniformly, and then cooling the mixture to obtain a gelatin gel;

[0009] S3: drying the gelatin gel prepared in step S2, and crushing the dried gelatin gel to prepare pretreated gelatin powder;

[0010] S4: placing the pretreated gelatin powder obtained in step S3 and water together in a high-pressure reactor, and stirring them evenly to obtain a gelatin dispersion;

[0011] S5: adding a crosslinking agent to the gelatin dispersion obtained in step S4 and continuing to stir; and adding a physical foaming agent into the autoclave to raise the pressure in the autoclave to a first pressure;

[0012] S6: After the first time interval, stirring is stopped and the pressure in the high-pressure reactor is released to obtain gelatin sponge particles.

[0013] Preferably, drying the gelatin gel prepared in step S2 specifically comprises:

[0014] drying or freeze-drying the gelatin gel;

[0015] If the gelatin gel is dried, the drying temperature is controlled at 30°C-60°C; if the gelatin gel is freeze-dried, the freeze-drying temperature is controlled at -50°C to -10°C.

[0016] Preferably, the step of crushing the dried gelatin gel to obtain pretreated gelatin powder specifically comprises:

[0017] crushing the dried gelatin gel to obtain a first gelatin powder;

[0018] Sieving the first gelatin powder into a second gelatin powder having a particle size of 10 μm to 700 μm;

[0019] Wherein, the pretreated gelatin powder is the second gelatin powder.

[0020] Preferably, the temperature of the water in step S4 is controlled at 10°C to 30°C.

[0021] Preferably, the stirring speed in step S5 is controlled at 100 rpm to 500 rpm.

[0022] Preferably, the mass of the cross-linking agent added in step S5 accounts for 1% to 20% of the mass of the pretreated gelatin powder.

[0023] Preferably, the first pressure is 1 MPa to 8 MPa.

[0024] Preferably, the first time interval is 10 minutes to 120 minutes.

[0025] Preferably, the water in steps S1 and S4 is sterile water.

[0026] Preferably, the heating temperature in step S1 is controlled at 45°C to 55°C.

[0027] The present invention provides a method for synthesizing gelatin sponge particles, which comprises the following steps: first dissolving gelatin and then mixing it with a water-soluble developer, then cooling the mixture to obtain a gelatin gel with a developing effect, then drying and crushing the gelatin gel to obtain a pretreated gelatin powder with uniform particles, and then mixing the gelatin powder, a cross-linking agent, and a physical foaming agent in water and cross-linking to form developable gelatin sponge particles with relatively uniform particle size. This method solves the problems in the background art that the production of gelatin sponge particles easily causes the destruction of the pore structure and the uncontrollable particle morphology, and the like. DETAILED DESCRIPTION

[0028] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention is described in detail below. The description in this section is only exemplary and explanatory and should not have any limiting effect on the scope of protection of the present invention.

[0029] This embodiment provides a method for synthesizing gelatin sponge particles, comprising the following steps:

[0030] Step 1: Place gelatin in water, allow it to swell, and then heat to dissolve to prepare a gelatin solution.

[0031] Step 2: Add a water-soluble developer to the gelatin solution prepared in step 1 and stir evenly, and then cool to obtain a gelatin gel.

[0032] Step 3: Dry the gelatin gel prepared in step 2, and crush the dried gelatin gel to obtain pretreated gelatin powder.

[0033] Step 4: Place the pretreated gelatin powder obtained in step 3 and water in a high-pressure reactor, and stir them evenly to obtain a gelatin dispersion.

[0034] Step 5: Add a cross-linking agent to the gelatin dispersion prepared in step 4 and continue stirring; and add a physical foaming agent into the high-pressure reactor to increase the pressure in the reactor to the first pressure.

[0035] Step 6: After the first time interval, stirring is stopped and the pressure in the autoclave is released to obtain gelatin sponge particles.

[0036] Specifically, in step 1, the gelatin can be gelatin powder or gelatin particles. After the gelatin is placed in water, the gelatin will absorb water and swell. After heating, the gelatin will dissolve to form a gelatin solution; in step 2, a water-soluble developer, such as iohexol, iotrolan, etc., is added to the gelatin solution, and stirred evenly to allow the developer and gelatin to fully fuse together. When cooled to 35°C to 40°C or below, it condenses to form a gelatin gel; in step 3, the gelatin gel is dried and crushed to form a gelatin powder. At this time, the particle size of the powder is uneven, and the gelatin powder can be sieved through a sieve to obtain the gel powder of the particle size; in step 4, the gelatin powder of the desired particle size and water are stirred together in a high-pressure reactor to disperse the gel powder in water. It should be noted that in order to avoid the gel powder dissolving in water, the water temperature must be below the dissolution temperature of the gel, usually 45°C to 40°C. Below 55°C; Step 5: Add the cross-linking agent and the physical foaming agent into the reactor together, and continue to stir the gelatin dispersion so that the gelatin powder can be continuously suspended and dispersed. It should be noted that the physical foaming agent added in this embodiment is a gas. After the physical foaming agent is added, the air pressure in the autoclave rises. Under continuous stirring and high pressure, the cross-linking agent and the physical foaming agent are evenly and quickly immersed in the pretreated gelatin powder, and gradually cause the gelatin powder to undergo a cross-linking reaction. The mechanical strength of the gelatin powder is improved to prevent it from further swelling and maintain a certain particle size and morphology. In step 6, when the infiltration reaches the appropriate time, the pressure in the autoclave is released, and the physical foaming agent in the gelatin powder expands, thereby obtaining gelatin sponge particles in a cellular state. The speed of pressure release can be adjusted to obtain open-pore or closed-pore sponge particles with uniform cellular state. Since the pretreated gelatin powder is a sieved gelatin powder with a relatively uniform particle size, the particle size of the gelatin sponge particles finally obtained is also relatively uniform.

[0037] The present embodiment provides a method for synthesizing gelatin sponge particles, which comprises first dissolving gelatin and then mixing it with a water-soluble developer, then cooling the mixture to obtain a gelatin gel with a developing effect, and then drying and crushing the gelatin gel to obtain a pretreated gelatin powder with uniform particles. The gelatin powder, a cross-linking agent, and a physical foaming agent are mixed in water and cross-linked to form developable gelatin sponge particles with relatively uniform particle size. This solves the problems in the background art that the production of gelatin sponge particles may easily cause the destruction of the pore structure and the uncontrollable particle morphology.

[0038] Furthermore, the drying method of the gelatin gel specifically includes drying or freeze-drying.

[0039] If the gelatin gel is dried, the drying temperature needs to be controlled at 30°C-60°C; if the gelatin gel is freeze-dried, the freeze-drying temperature needs to be controlled at -50°C to -10°C.

[0040] Furthermore, crushing the dried gelatin gel specifically comprises the following steps:

[0041] Step 1: Grind the dried gelatin gel to obtain a first gelatin powder.

[0042] Step 2: Sieve the first gelatin powder to obtain a second gelatin powder having a particle size of 10 μm to 700 μm.

[0043] Wherein, the pretreated gelatin powder is the second gelatin powder.

[0044] Specifically, the particle size of the gelatin powder after drying and crushing is uneven. The gelatin powder can be first screened into the required particle size through a sieve or other structure, and then the screened gelatin powder can be used to prepare gelatin sponge particles to obtain gelatin sponge particles with uniform particle size and the required particle size.

[0045] Among them, after the pressure in the high-pressure reactor is released, the physical foaming agent will expand and stretch the pretreated gelatin powder from the inside to make it larger. When the particle size of the gelatin powder expands, the content of the physical foaming agent that can be accommodated also increases. However, since the foaming ratio of the physical foaming agent is affected by many factors such as pressure and foaming time, the magnification ratio of the gelatin sponge particle size relative to the pretreated gelatin powder particle size is not fixed. In the embodiment provided in this embodiment, the particle size of the pretreated gelatin powder is 10μm to 700μm, and the particle size of the prepared gelatin sponge particles is 11μm to 3000μm, that is, the particle size growth range of the gelatin sponge particles is approximately 1.1 to 4.3 times the size of the pretreated gelatin powder.

[0046] Furthermore, the temperature of water in step 4 is controlled at 10° C. to 30° C. to prevent gelatin powder from dissolving in water.

[0047] Furthermore, in step 5, the stirring speed is controlled at 100 rpm to 500 rpm to facilitate the suspension and dispersion of the gelatin powder and to facilitate the infiltration of the cross-linking agent and the physical foaming agent into the pretreated gelatin powder.

[0048] Furthermore, the mass of the cross-linking agent added in step 5 accounts for 1% to 20% of the mass of the pretreated gelatin powder.

[0049] Among them, since the cross-linking agent is used for the solidification and shaping of gelatin, it can affect the mechanical properties of the gelatin sponge particles, and the amount of the cross-linking agent can be adjusted as needed.

[0050] Furthermore, the first pressure is 1 MPa to 8 MPa.

[0051] Among them, since the physical foaming agent expands due to the release of pressure after pressurization, the physical foaming agent inside the gelatin powder expands it. The magnitude of the first pressure can affect the expansion ratio of the physical foaming agent, thereby changing the size of the gelatin sponge particles and the water absorption effect of the gelatin sponge particles. Therefore, the magnitude of the first pressure can be adjusted as needed.

[0052] Furthermore, the first time interval is 10 minutes to 120 minutes.

[0053] The stirring time can affect the degree to which the cross-linking agent and the physical foaming agent infiltrate the gelatin powder, thereby changing the size of the obtained gelatin sponge particles. The length of the first time can be adjusted as needed.

[0054] Furthermore, the water in step 1 and step 4 is sterile water to avoid contamination of the prepared gelatin sponge particles.

[0055] Furthermore, the heating temperature in step 1 is controlled at 45° C. to 55° C. to fully dissolve the gelatin.

[0056] Two specific embodiments are provided below. The provided embodiments may enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way.

[0057] Example 1: Animal-derived gelatin is swelled in water and then heated and stirred to dissolve. Iodine trolam is added as a water-soluble developer and continued to be stirred evenly. The temperature is lowered to make it gel. The gelatin gel with the water-soluble developer is dried at 50°C and then crushed. It is sieved into pretreated gelatin powder of 50 μm to 100 μm. The pretreated gelatin powder is placed in a high-pressure reactor filled with water and stirred and dispersed. The water temperature is controlled at 20°C and the stirring speed is 200 rpm. Glutaraldehyde is added as a cross-linking agent at a concentration of 5% by weight of the pretreated gelatin powder. CO2 gas is introduced as a physical foaming agent to raise the pressure in the high-pressure reactor to 1 MPa. After 30 minutes, the pressure is released to obtain developable gelatin sponge particles with a particle size of 55 μm to 110 μm.

[0058] Example 2: Animal-derived gelatin is swelled in water and then heated and stirred to dissolve. Iodine troleum is added as a water-soluble developer and continued to be stirred evenly. The temperature is lowered to make it gel. The gelatin gel with the water-soluble developer is dried at 50°C and then crushed. It is sieved into pretreated gelatin powder of 650 μm to 700 μm. The pretreated gelatin powder is placed in a high-pressure reactor filled with water and stirred and dispersed. The water temperature is controlled at 25°C and the stirring speed is 300 rpm. Glutaraldehyde is added as a cross-linking agent in an amount of 10% by mass of the pretreated gelatin powder. CO2 gas is introduced as a physical foaming agent to raise the pressure in the high-pressure reactor to 8 MPa. After 100 minutes, the pressure is released to obtain developable gelatin sponge particles with a particle size of 2800 μm to 3000 μm.

[0059] Working principle: After gelatin is placed in water, it will absorb water and swell. After heating, the gelatin will dissolve to form a gelatin solution; add a water-soluble developer, such as iohexol, iotrolan, etc., to the gelatin solution and stir evenly to make the developer and gelatin fully blend together. When cooled to 35°C to 40°C or below, it condenses to form a gelatin gel; the gelatin gel is dried and crushed to make a gel powder. At this time, the particle size of the powder is uneven. The gel powder can be sieved through a sieve to obtain the gel powder of the particle size; the gel powder of the desired particle size is stirred together with water in a high-pressure reactor to disperse the gel powder in the water. In order to avoid the gel powder dissolving in the water, the water temperature must be below the dissolution temperature of the gel, usually below 45°C to 55°C; the cross-linked The cross-linking agent and the physical foaming agent are added to the reactor together, and the gelatin dispersion is continuously stirred to allow the gelatin powder to be continuously suspended and dispersed. The added physical foaming agent is a gas. After the physical foaming agent is added, the air pressure in the autoclave rises. Under the continuous stirring and high pressure, the cross-linking agent and the physical foaming agent are uniformly and quickly immersed in the pretreated gelatin powder, and the gelatin powder is gradually cross-linked. The mechanical strength of the gelatin powder is improved, which prevents it from further swelling and maintains a certain particle size and morphology. When the infiltration reaches a suitable time, the pressure in the autoclave is released, and the physical foaming agent in the gelatin powder expands, thereby obtaining gelatin sponge particles in a cellular state. The speed of pressure release can be adjusted to obtain open-pore or closed-pore sponge particles with uniform cellular state. Since the pretreated gelatin powder is screened gelatin powder with relatively uniform particle size, the particle size of the gelatin sponge particles finally obtained is also relatively uniform.

[0060] It should be noted that, in this article, the terms "comprises", "includes" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or apparatus that includes a series of elements includes not only those elements, but also includes other elements not explicitly listed, or also includes elements that are inherent to such process, method, article or apparatus.

[0061] This article uses specific examples to illustrate the principles and implementation methods of the present invention. The description of the above embodiments is only used to help understand the method and core ideas of the present invention. The above are only preferred implementation methods of the present invention. For ordinary technicians in this technical field, without departing from the principles of the present invention, several improvements, modifications or changes can be made, and the above technical features can be combined in an appropriate manner; these improvements, modifications, changes or combinations, or the direct application of the inventive concept and technical solution to other occasions without modification, should be considered as the scope of protection of the present invention.

Claims

1. A method for synthesizing gelatin sponge particles, characterized in that: The steps include: S1: Place gelatin in water, allow it to swell, and then heat to dissolve to prepare a gelatin solution; S2: adding a water-soluble developer to the gelatin solution prepared in step S1 and stirring the mixture uniformly, and then cooling the mixture to obtain a gelatin gel; S3: drying the gelatin gel prepared in step S2, and crushing the dried gelatin gel to prepare pretreated gelatin powder; S4: placing the pretreated gelatin powder obtained in step S3 and water together in a high-pressure reactor, and stirring them evenly to obtain a gelatin dispersion; S5: adding a crosslinking agent to the gelatin dispersion obtained in step S4 and continuing to stir; and adding a physical foaming agent into the autoclave to raise the pressure in the autoclave to a first pressure; S6: After the first time interval, stirring is stopped and the pressure in the high-pressure reactor is released to obtain gelatin sponge particles.

2. The method according to claim 1, characterized in that The step of drying the gelatin gel prepared in step S2 specifically comprises: drying or freeze-drying the gelatin gel; If the gelatin gel is dried, the drying temperature is controlled at 30°C-60°C; if the gelatin gel is freeze-dried, the freeze-drying temperature is controlled at -50°C to -10°C.

3. The method according to claim 1, characterized in that The method of crushing the dried gelatin gel to obtain the pretreated gelatin powder specifically comprises: crushing the dried gelatin gel to obtain a first gelatin powder; Sieving the first gelatin powder into a second gelatin powder having a particle size of 10 μm to 700 μm; Wherein, the pretreated gelatin powder is the second gelatin powder.

4. The method according to claim 1, wherein In step S4, the temperature of the water is controlled at 10°C to 30°C.

5. The method according to claim 1, wherein In step S5, the stirring speed is controlled at 100 rpm to 500 rpm.

6. The method according to claim 1, characterized in that The mass of the cross-linking agent added in step S5 accounts for 1% to 20% of the mass of the pretreated gelatin powder.

7. The method according to claim 1, characterized in that The first pressure is 1 MPa to 8 MPa.

8. The method according to claim 1, characterized in that The first time interval is 10 minutes to 120 minutes.

9. The method according to any one of claims 1 to 8, characterized in that The water in steps S1 and S4 is sterile water.

10. The method according to any one of claims 1 to 8, characterized in that The heating temperature in step S1 is controlled at 45°C to 55°C.