CN113717409A - Injectable plasma activated hydrogel and preparation method thereof - Google Patents
Injectable plasma activated hydrogel and preparation method thereof Download PDFInfo
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- CN113717409A CN113717409A CN202110962011.8A CN202110962011A CN113717409A CN 113717409 A CN113717409 A CN 113717409A CN 202110962011 A CN202110962011 A CN 202110962011A CN 113717409 A CN113717409 A CN 113717409A
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Abstract
An injectable plasma activated hydrogel and a preparation method thereof, comprising the following steps: the hydrogel material and the solution are mixed according to the mass ratio of 1:5, and the hydrogel material is a (polylactic acid-polyethylene glycol-polylactic acid) n polymer. According to the invention, the temperature-sensitive hydrogel solution is subjected to plasma activation treatment, and a large number of active particles are introduced on the basis of not changing the original good biocompatibility of the hydrogel; meanwhile, the plasma activated hydrogel can continuously play a role in a focus part, compared with plasma activated water, the service life of active particles in the hydrogel is effectively prolonged, the defect that the plasma activated water has fluidity is overcome, and the medical application potential of the plasma is improved.
Description
Technical Field
The invention relates to the technical field of atmospheric pressure cold plasmas, in particular to an injectable plasma activated hydrogel and a preparation method thereof.
Background
Plasma is a fourth state of matter, except solid, liquid, gas. The low-temperature plasma generated in the atmospheric pressure environment contains a plurality of active particles, and the active particles have biomedical effects of sterilization, cancer resistance, wound healing promotion and the like. Although low-temperature plasma has great potential for medical application, the penetration of active particles is weak, and the active particles are attenuated quickly, so that the plasma is difficult to be directly applied to the continuous treatment of the focus in the deep part of the body. Although the plasma activated water can be used as a medium of active particles to break through the limitation of penetration depth, the mobility of the plasma activated water along with the circulation of the liquid makes it difficult to continuously act on the same lesion site. The drawbacks of the above plasma technology make its application in the medical field limited.
Disclosure of Invention
The invention aims to provide an injectable plasma activated hydrogel and a preparation method thereof, so as to solve the problems.
In order to achieve the purpose, the invention adopts the following technical scheme:
an injectable plasma-activated hydrogel comprising: the hydrogel material and the solution are mixed according to the mass ratio of 1:5, and the hydrogel material is a (polylactic acid-polyethylene glycol-polylactic acid) n polymer.
Further, the hydrogel material is (polylactic acid-polyethylene glycol-polylactic acid) 200, (polylactic acid-polyethylene glycol-polylactic acid) 185 or (polylactic acid-polyethylene glycol-polylactic acid) 205.
Further, the solution is medical purified water, buffer solution or normal saline.
Further, the preparation method of the injectable plasma activated hydrogel comprises the following steps:
step 1, mixing and stirring a hydrogel material and a solution until the hydrogel material and the solution are completely dissolved to prepare a hydrogel solution;
step 2, carrying out plasma activation treatment on the prepared hydrogel solution to generate a plasma activated hydrogel solution;
and 3, when the temperature of the plasma activated hydrogel solution rises to the phase transition temperature, the hydrogel solution is gelled and spontaneously converted from the solution state to the gel state.
Further, in step 1, a magnetic stirrer is used for mixing and stirring.
Further, in step 2, the discharge mode for generating plasma is atmospheric pressure cold plasma discharge, including dielectric barrier discharge, corona discharge, sliding arc discharge or jet discharge.
Further, in step 3, the phase transition temperature is a critical temperature value of the hydrogel transforming from the solution state to the gel state.
Further, in step 3, the phase transition temperature is the normal body temperature value of the human body.
Compared with the prior art, the invention has the following technical effects:
according to the invention, the temperature-sensitive hydrogel solution is subjected to plasma activation treatment, and a large number of active particles are introduced on the basis of not changing the original good biocompatibility of the hydrogel; meanwhile, the plasma activated hydrogel can continuously play a role in a focus part, compared with plasma activated water, the service life of active particles in the hydrogel is effectively prolonged, the defect that the plasma activated water has fluidity is overcome, and the medical application potential of the plasma is improved. In addition, the plasma activated hydrogel can be simultaneously used as a drug slow release carrier, and is suitable for various scenes in the clinical application process.
Drawings
Various other advantages and benefits of the present invention will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention. It is obvious that the drawings described below are only some embodiments of the invention, and that for a person skilled in the art, other drawings can be derived from them without inventive effort.
In the drawings:
FIG. 1 is a schematic diagram of a process for preparing an injectable plasma-activated hydrogel according to one embodiment of the present invention.
Figure 2 is a schematic illustration of injection of a plasma-activated hydrogel for clinical treatment of cancer, according to one embodiment of the present invention.
FIG. 3 is a graph of the effect of plasma activated gelatin on cancer therapy.
Detailed Description
Specific embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. While specific embodiments of the invention are shown in the drawings, it should be understood that the invention may be embodied in various forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
It should be noted that certain terms are used throughout the description and claims to refer to particular components. As one skilled in the art will appreciate, various names may be used to refer to a component. This specification and claims do not intend to distinguish between components that differ in name but not function. In the following description and in the claims, the terms "include" and "comprise" are used in an open-ended fashion, and thus should be interpreted to mean "include, but not limited to. The description which follows is a preferred embodiment of the invention, but is made for the purpose of illustrating the general principles of the invention and not for the purpose of limiting the scope of the invention. The scope of the present invention is defined by the appended claims.
For the purpose of facilitating an understanding of the embodiments of the present invention, the following detailed description will be given by way of example with reference to the accompanying drawings, which are not intended to limit the embodiments of the present invention.
The invention relates to a preparation method of injectable plasma activated hydrogel. The gel material used in the invention is (polylactic acid-polyethylene glycol-polylactic acid) n polymer, when preparing injectable plasma activated hydrogel, firstly, the gel material is mixed with the solution at room temperature (about 25 ℃) to prepare hydrogel solution with specific concentration; then, activating the hydrogel solution by using a low-temperature plasma device to prepare a plasma activated hydrogel solution; finally, the plasma activated hydrogel solution is injected into a focus part in an organism, and can be gelled under the condition of body temperature (about 35 ℃), so that the gel is converted into a gel state and is gradually degraded at the focus part, and the gel has a biomedical effect. When preparing the plasma activated hydrogel, firstly adding a solution and a gel material into a container, and fully mixing the solution and the gel material to obtain a hydrogel solution; then, activating the hydrogel solution by using a low-temperature plasma device to prepare the plasma activated hydrogel solution; and finally, injecting the plasma activated hydrogel solution into the focus part of the organism to enable the gel solution to reach the phase transition temperature under the action of body temperature to generate gelation, and finally converting the plasma activated hydrogel solution into the plasma activated hydrogel. The plasma activated hydrogel contains abundant plasma active particles, exerts biomedical effect in a body and is expected to be widely applied in the field of medical treatment.
For a better understanding, as shown in figure 1,
example 1:
a preparation method of injectable plasma activated hydrogel comprises preparing hydrogel solution by mixing hydrogel material with the solution; mixing a hydrogel material and the solution according to a mass ratio of 1:5, wherein the hydrogel material is (polylactic acid-polyethylene glycol-polylactic acid) 200.
A plasma activation treatment step of treating the hydrogel solution by a plasma activation device to generate a plasma activated hydrogel solution;
the plasma activated hydrogel is converted from a solution state to a gel state, and when the temperature of the plasma activated hydrogel solution rises to a phase-change temperature, the hydrogel solution is subjected to gelation, and is spontaneously converted from the solution state to the gel state.
Example 2:
a preparation method of injectable plasma activated hydrogel comprises preparing hydrogel solution by mixing hydrogel material with the solution; mixing the hydrogel material and the solution according to the mass ratio of 1:5, wherein the hydrogel material is (polylactic acid-polyethylene glycol-polylactic acid) 185.
A plasma activation treatment step of treating the hydrogel solution by a plasma activation device to generate a plasma activated hydrogel solution;
the plasma activated hydrogel is converted from a solution state to a gel state, and when the temperature of the plasma activated hydrogel solution rises to a phase-change temperature, the hydrogel solution is subjected to gelation, and is spontaneously converted from the solution state to the gel state.
Example 3:
a preparation method of injectable plasma activated hydrogel comprises preparing hydrogel solution by mixing hydrogel material with the solution; mixing the hydrogel material and the solution according to the mass ratio of 1:5, wherein the hydrogel material is (polylactic acid-polyethylene glycol-polylactic acid) 205.
A plasma activation treatment step of treating the hydrogel solution by a plasma activation device to generate a plasma activated hydrogel solution;
the plasma activated hydrogel is converted from a solution state to a gel state, and when the temperature of the plasma activated hydrogel solution rises to a phase-change temperature, the hydrogel solution is subjected to gelation, and is spontaneously converted from the solution state to the gel state.
The invention integrates the advantages of the plasma and the temperature-sensitive hydrogel. The prepared plasma activated hydrogel introduces a large amount of active particles on the basis of not changing the original good biocompatibility of the hydrogel; meanwhile, the plasma activated hydrogel can continuously play a role in a focus part, compared with plasma activated water, the service life of active particles in the hydrogel is effectively prolonged, the defect that the plasma activated water has fluidity is overcome, and the medical application potential of the plasma is improved. In addition, the plasma activated hydrogel can be simultaneously used as a drug slow release carrier, realizes the synergistic effect of active particles and drug molecules, and is suitable for various scenes in the clinical application process.
In a preferred embodiment of the injectable plasma-activated hydrogel preparation method, as shown in fig. 1, the temperature-sensitive hydrogel solution is prepared by fully mixing the solution in a container and added hydrogel materials.
More preferably, the solution includes purified water for medical use, a buffer, physiological saline, and the like.
Preferably, a magnetic stirrer is used to mix the solution with the hydrogel material added to the vessel when preparing the temperature sensitive hydrogel solution.
In a preferred embodiment of the injectable plasma-activated hydrogel preparation method, in the plasma activation treatment step, a plasma activation device is used to treat a hydrogel solution to generate a plasma-activated hydrogel solution, and the discharge mode for generating plasma is atmospheric pressure cold plasma discharge, including dielectric barrier discharge, corona discharge, sliding arc discharge, jet discharge and the like;
in a preferred embodiment of the method for preparing the injectable plasma-activated hydrogel, the injectable plasma-activated hydrogel is transformed from a solution state to a gel state, which is a spontaneous gelation effect of the gel when the temperature of the solution reaches the phase transition temperature, and can occur when the plasma-activated hydrogel solution is injected into a body, and the plasma-activated hydrogel solution is rapidly transformed into the gel which can be degraded by the body on the body surface or in the body.
In a preferred embodiment of the injectable plasma activated hydrogel preparation method, the hydrogel material is a high molecular material which has good biocompatibility, can be degraded in a body and is sensitive to temperature, such as a (polylactic acid-polyethylene glycol-polylactic acid) n polymer material.
In the preferred embodiment of the preparation method of the injectable plasma activated hydrogel, when the temperature is lower than the phase transition temperature, the hydrogel solution keeps a solution state and cannot be spontaneously converted into a gel state, when the temperature reaches the phase transition temperature, the hydrogel can be converted from the solution state into the gel state, and the plasma active particles in the hydrogel are stably released from the inside of the hydrogel under the promotion of diffusion and hydrogel degradation, so that the long-acting slow-release treatment effect is achieved.
In a preferred embodiment of the preparation method of the injectable plasma activated hydrogel, the phase transition temperature is a critical temperature value of the hydrogel in a solution state and a gel state, and is related to factors such as the type and the molecular weight of a hydrogel material, for example, a phase transition temperature of a hydrogel solution prepared by dissolving a (poly (lactic acid) -poly (ethylene glycol) -poly (lactic acid)) n polymer material with a specific molecular weight is close to a normal body temperature value of a human body, namely about 35 ℃.
As shown in fig. 2, a plasma-activated hydrogel solution is injected for cancer treatment according to one embodiment of the present invention. The injectable plasma activated hydrogel solution is injected into the cancerous lesion of a patient to achieve a sustained local anticancer therapeutic effect.
Alternatively, plasma activated hydrogels are used in conjunction with surgical procedures for the clinical treatment of cancer. After the tumor focus is removed by operation, injectable plasma activated hydrogel is filled to the position of a postoperative incision, and the wound is sutured and bound, so that the effect of inhibiting the in-situ recurrence of the postoperative tumor is realized.
As shown in fig. 3, the inhibition of tumor cell growth by the activated hydrogel was observed using plasma activated hydrogel to inhibit 3D bladder cancer tumor models (T24 cells) cultured in vitro, according to one embodiment of the present invention. The result shows that the plasma activated hydrogel can effectively inhibit the growth of cancer cells, and the stronger the inhibition effect on the cancer cells along with the increase of the plasma activation strength.
It can be understood that the injectable plasma-activated hydrogel prepared by the preparation method is used in the medical field.
The foregoing describes the general principles of the present application in conjunction with specific embodiments thereof, however, it is noted that the advantages, effects, etc. mentioned in the present application are exemplary only and not limiting, and should not be considered essential to the various embodiments of the present application. Furthermore, the foregoing disclosure of specific details is for the purpose of illustration and description and is not intended to be limiting, since the foregoing disclosure is not intended to be exhaustive or to limit the disclosure to the precise details disclosed.
The foregoing description has been presented for purposes of illustration and description. Furthermore, the description is not intended to limit embodiments of the application to the form disclosed herein. While a number of example aspects and embodiments have been discussed above, those of skill in the art will recognize certain variations, modifications, alterations, additions and sub-combinations thereof.
Claims (8)
1. An injectable plasma-activated hydrogel, comprising: the hydrogel material and the solution are mixed according to the mass ratio of 1:5, and the hydrogel material is a (polylactic acid-polyethylene glycol-polylactic acid) n polymer.
2. An injectable plasma-activated hydrogel according to claim 1, wherein the hydrogel material is (poly (lactic acid) -poly (ethylene glycol) -poly (lactic acid)) 200, (poly (lactic acid) -poly (ethylene glycol) -poly (lactic acid)) 185 or (poly (lactic acid) -poly (ethylene glycol) -poly (lactic acid)) 205.
3. An injectable plasma-activated hydrogel according to claim 1 wherein the solution is purified medical water, buffer or physiological saline.
4. A method for producing an injectable plasma-activated hydrogel, which is based on the injectable plasma-activated hydrogel of any one of claims 1 to 3, comprising the steps of:
step 1, mixing and stirring a hydrogel material and a solution until the hydrogel material and the solution are completely dissolved to prepare a hydrogel solution;
step 2, carrying out plasma activation treatment on the prepared hydrogel solution to generate a plasma activated hydrogel solution;
and 3, when the temperature of the plasma activated hydrogel solution rises to the phase transition temperature, the hydrogel solution is gelled and spontaneously converted from the solution state to the gel state.
5. The method for preparing an injectable plasma-activated hydrogel according to claim 2, wherein in the step 1, a magnetic stirrer is used for mixing and stirring.
6. The method for preparing an injectable plasma-activated hydrogel according to claim 2, wherein in step 2, the discharge mode for generating plasma is atmospheric pressure cold plasma discharge, including dielectric barrier discharge, corona discharge, sliding arc discharge or jet discharge.
7. The method according to claim 2, wherein the phase transition temperature in step 3 is a critical temperature for the hydrogel to transform from a solution state to a gel state.
8. The method according to claim 7, wherein the phase transition temperature in step 3 is a normal body temperature of a human body.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070010596A1 (en) * | 2005-07-08 | 2007-01-11 | Georgia Tech Research Corporation | Plasma-Polymerized Hydrogel Thin Films and Methods for Making the Same |
| CN112022797A (en) * | 2020-07-24 | 2020-12-04 | 西安交通大学 | Preparation method of temperature-sensitive plasma active biogel and active biogel |
| CN112125374A (en) * | 2020-09-14 | 2020-12-25 | 西安交通大学 | Method and device for preserving plasma activated water and method for preparing finished product |
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- 2021-08-20 CN CN202110962011.8A patent/CN113717409A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070010596A1 (en) * | 2005-07-08 | 2007-01-11 | Georgia Tech Research Corporation | Plasma-Polymerized Hydrogel Thin Films and Methods for Making the Same |
| CN112022797A (en) * | 2020-07-24 | 2020-12-04 | 西安交通大学 | Preparation method of temperature-sensitive plasma active biogel and active biogel |
| CN112125374A (en) * | 2020-09-14 | 2020-12-25 | 西安交通大学 | Method and device for preserving plasma activated water and method for preparing finished product |
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Application publication date: 20211130 |