Radical- and photothermal reaction-inducing polymer degradation composite

Abstract

The present invention relates to a composite that promotes polymer degradation by inducing radical generation and photothermal reactions. The composite has a core-shell structure and comprises: a core that generates radicals in response to ultrasound; and a photothermal conversion carrier shell that induces heat generation upon near-infrared irradiation. The present composite may be applied to a polymer structure inserted into a living body to precisely induce polymer chain scission and degradation according to external stimuli. Through this, the biodegradation rate may be accelerated and in vivo safety may be ensured.

Description

Radical and photothermal reaction-induced polymer decomposition complex

[0001] The present invention relates to a composite for inducing the degradation of a polymer material, and more specifically, to a core-shell structured composite capable of non-invasively inducing the degradation of an implantable polymer-based device by utilizing a photothermal reaction and radical generation.

[0002] In particular, the present invention relates to a technology capable of effectively cleaving polymer chains and promoting degradation through photothermal effects caused by near-infrared (NIR) irradiation and radical generation caused by ultrasonic stimulation, and relates to a biocompatible composite that can be usefully applied to control and accelerate the degradation of medical polymer materials that biodegrade and naturally disappear after performing a function in the body for a specific period.

[0003] With the advancement of medical technology, polymer-based medical implants inserted into the body for purposes such as tissue regeneration, nerve reconstruction, and fracture treatment are widely used. These implantable medical devices must naturally decompose within the body after performing the function of supporting or protecting tissues for a certain period, so that they can be safely excreted or absorbed without the need for a second surgery. Accordingly, polymeric biodegradable materials are being actively developed; however, there are limitations in effectively controlling or accelerating the rate of degradation in the actual in vivo environment.

[0004] Previously, methods involving the ex vivo addition of enzymes were used to promote polymer degradation; however, it is difficult to deliver external enzymes or ensure they act precisely on the reaction site within the in vivo environment. Accordingly, methods utilizing high-intensity ultrasound to physically fragment polymer implants or increase their surface area to accelerate hydrolysis have recently been proposed; however, these methods also face technical limitations due to the need for localized and direct stimulation and the difficulty in controlling degradation.

[0005] Therefore, there is an urgent need for technology capable of precisely inducing and controlling the degradation of polymer materials inserted into the body in a non-invasive manner—specifically, the development of a new mechanism that can cleave polymer chains by generating radicals internally or inducing localized heat in response to external stimuli.

[0006] The present invention relates to a composite capable of selectively cleaving polymer chains and inducing degradation in response to externally applied stimuli, and in particular, is applied to a polymer-based medical device inserted into the body, and has the main objective of enabling spontaneous or controlled degradation in response to external stimuli after performing a function for a certain period.

[0007] The present invention aims to provide a novel composite capable of non-invasively and precisely controlling the degradation of implantable polymer materials by simultaneously utilizing two mechanisms: radical generation and photothermal reaction.

[0008] A radical and photothermal reaction-inducing polymer decomposition composite according to one embodiment of the present invention comprises: a core having a core-shell structure and including a radical-generating material that cleaves polymer chains; and a shell including a photothermal conversion carrier material that promotes polymer chain cleaving through heat generation by near-infrared irradiation.

[0009] The above radical generating material generates radicals upon the application of ultrasound. The above radical generating material includes one or more of AIPH (2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride), 4,4'-Azobis(4-cyanopentanoic acid), BaTiO3, curcumin, methylene blue, and indocyanine green.

[0010] The above photothermal conversion carrier material includes metal organic framework (MOF) material, MXene, polydopamine, or gold nanocages.

[0011] The above MOF material includes MIL-100(Fe) or MIL-101(Fe).

[0012] The above photothermal conversion carrier material generates heat when near-infrared (NIR) is applied.

[0013] When the photothermal conversion carrier material is heated by the above near-infrared rays, it is preferable to control the wavelength and intensity of the light so that the heating temperature is between about 36°C and 40°C so as not to affect the body.

[0014] Preferably, the wavelength of the light is 700 to 850 nm, and the intensity of the light is 0.5 to 2.0 W / cm² 2 It is desirable that it is.

[0015] A polymer-based implantable device according to one embodiment of the present invention comprises a radical and photothermal reaction-induced polymer decomposition complex, and the polymer-based implantable device can decompose the polymer by applying near-infrared rays and ultrasound after performing a function in the body for a certain period of time.

[0016] The radical and photothermal reaction-induced polymer degradation composite according to the present invention provides an innovative means to locally and precisely control the degradation of a polymer-based medical device inserted into the body in response to external stimuli such as ultrasound and near-infrared (NIR).

[0017] This complex generates radicals upon the application of ultrasound to directly cleave polymer chains, thereby reducing molecular weight and weakening the structure of the polymer to induce degradation. Compared to conventional methods that rely on simple heat or enzymes, this allows for more effective promotion of the degradation reaction by incorporating a chemical cleavage mechanism.

[0018] FIG. 1 illustrates a schematic design of a radical and photothermal reaction-induced polymer decomposition composite according to one embodiment of the present invention.

[0019] Figure 2 illustrates the verification of radical generation and photothermal reaction effects of a polymer decomposition promoting material.

[0020] Figure 3 shows a graph of light absorption by wavelength for MIL-100 (Fe).

[0021] Various embodiments are now described with reference to the drawings, and throughout the drawings, similar reference numerals are used to denote similar elements. For illustrative purposes, various descriptions are provided in this specification to facilitate an understanding of the invention. However, it is evident that these embodiments can be practiced without such specific descriptions. In other examples, known structures and devices are presented in the form of block diagrams to facilitate the description of the embodiments.

[0022] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings. As the present invention is susceptible to various modifications and may take various forms, specific embodiments are illustrated in the drawings and described in detail in the text. However, this is not intended to limit the present invention to the specific disclosed forms, and it should be understood that the invention includes all modifications, equivalents, and substitutions that fall within the spirit and scope of the invention. Similar reference numerals have been used for similar components in the description of each drawing.

[0023] The terms used in this application are used merely to describe specific embodiments and are not intended to limit the invention. The singular expression includes the plural expression unless the context clearly indicates otherwise. In this application, terms such as "comprising" or "having" are intended to indicate the existence of the features, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, steps, actions, components, parts, or combinations thereof.

[0024] The present invention relates to a composite that promotes polymer decomposition by inducing radical generation and photothermal reactions, comprising a core having a core-shell structure that generates radicals in response to ultrasound, and a photothermal conversion carrier shell that induces heat generation upon near-infrared irradiation.

[0025] The photothermal conversion material included in the shell portion of the composite of the present invention induces localized heat generation upon irradiation with near-infrared rays (e.g., 808 nm), and is designed to operate particularly within a safe body temperature range of around 38°C, thereby accelerating the rate of decomposition without causing damage to body tissues. This allows for the safe induction of a decomposition reaction without tissue necrosis or inflammatory reactions caused by high temperature induction.

[0026] Furthermore, the composite of the present invention, designed with a core-shell structure, can be manufactured into particles ranging in size from tens of nanometers to several micrometers. This allows for easy mixing or embedding into biodegradable polymer films such as PLLA, and facilitates easy application to polymer structures in the form of devices. Therefore, it offers the advantage of replacing or supplementing existing polymer products to resolve delayed biodegradation and controlling the degradation timing according to user needs.

[0027] According to the present invention, a photothermal effect can be induced through external stimuli such as near-infrared (NIR) radiation to cause a localized temperature rise at specific parts of a polymer material, and a decomposition reaction can be accelerated through a process of cleaving polymer chains using radical-generating substances. Through this, it is possible to facilitate the spontaneous decomposition of the polymer material after it performs necessary functions within the body, allowing it to be excreted from the body or naturally absorbed within the body.

[0028] FIG. 1 illustrates a schematic design of a radical and photothermal reaction-induced polymer decomposition composite according to one embodiment of the present invention.

[0029] A radical and photothermal reaction-inducing polymer decomposition composite according to one embodiment of the present invention comprises: a core having a core-shell structure and including a radical-generating material that cleaves polymer chains; and a shell including a photothermal conversion carrier material that promotes polymer chain cleaving through heat generation by near-infrared irradiation.

[0030] Radical-generating substances generate radicals by applying ultrasound, and can reduce the molecular weight of polymers by cleaving polymer chains through radical generation.

[0031] Radical-generating substances include one or more of AIPH (2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride), 4,4'-Azobis(4-cyanopentanoic acid), BaTiO3, curcumin, methylene blue, and indocyanine green.

[0032] Photothermal conversion carrier materials are materials that generate heat when near-infrared (NIR) is applied, and photothermal conversion carrier materials include metal organic framework (MOF) materials, MXene, polydopamine, or gold nanocages.

[0033] In this case, the MOF material includes MIL-100(Fe) or MIL-101(Fe).

[0034] These photothermal conversion carrier materials form a shell and generate heat in response to near-infrared radiation, which can accelerate the rate of polymer decomposition. In the case of the composite of the present invention, photothermal heat generated in the shell structure upon near-infrared irradiation is transferred to the core, thereby further promoting the decomposition reaction of temperature-sensitive radical precursors (radical generating materials: AIPH, etc.) and consequently accelerating the polymer chain cleavage reaction. Therefore, the photothermal reaction and the radical generating reaction act complementarily to induce polymer decomposition more effectively.

[0035] The radical and photothermal reaction-inducing polymer decomposition composite according to the present invention comprises a photothermal conversion carrier material that generates heat in response to near-infrared (NIR) radiation, and it is preferable that this exothermic reaction be precisely controlled to a temperature between about 36°C and 40°C (preferably about 38°C) so as not to cause damage to body tissues.

[0036] To this end, the present invention ensures a balance between tissue safety and the effectiveness of the decomposition reaction by adjusting the wavelength and intensity of the light used according to the material properties.

[0037] Generally, near-infrared light with a wavelength of 700–850 nm can penetrate deeply into biological tissues and is a range capable of effectively delivering energy to polymeric structures within the body. Since implantable devices are typically located in the subcutaneous layer, light in a wavelength band of at least 700 nm is suitable.

[0038] The photothermal conversion carrier materials used in the present invention include MIL-100(Fe), MIL-101(Fe), MXene, polydopamine, and gold nanocages, and these materials exhibit different photothermal efficiencies depending on wavelength and intensity.

[0039] Figure 3 shows a graph of light absorption by wavelength for MIL-100 (Fe).

[0040] For MIL-100(Fe), 0.5 to 2.0 W / cm² at a wavelength of 700 to 850 nm, preferably 780 to 820 nm, and most preferably 808 nm. 2 , preferably 1.5 to 2.0 W / cm 2 It was possible to induce a temperature rise of approximately 38°C at the light intensity. For example, MIL-100(Fe) at a wavelength of 808 nm and 2.0 W / cm² 2 It was possible to induce a temperature rise of about 38°C at the light intensity inside and outside.

[0041] Polydopamine, MXene, MIL-101(Fe), and gold nanocages exert 0.5 to 1.0 W / cm² at a wavelength of 700 to 850 nm, preferably 780 to 820 nm, and most preferably 808 nm. 2 It was confirmed that a temperature of 38℃ or higher could be reached even at that intensity.

[0042] Under conditions defined in this manner, polymer chain cleavage and degradation can be effectively promoted by simultaneously inducing the thermal decomposition of radical precursors through a photothermal reaction, while preventing tissue damage within the body without excessive heat generation. Therefore, the present invention provides a technology optimized for precisely controlling and promoting polymer degradation reactions by inducing an exothermic reaction within a safe temperature range that does not cause tissue damage when applied to implantable polymer structures.

[0043] In summary, when using the radical and photothermal reaction-inducing polymer decomposition composite of the present invention, it is preferable to control the temperature of the heat generation of the photothermal conversion carrier material by adjusting the wavelength and intensity of the light so that the temperature is between approximately 36 and 40 degrees Celsius, so as not to affect the body when the photothermal conversion carrier material generates heat by near-infrared light; in this case, the wavelength of the light is 700 to 850 nm, and the intensity of the light is 0.5 to 2.0 W / cm². 2 It could be.

[0044] The radical and photothermal reaction-inducing polymer degradation composite according to the present invention is not limited to a simple degradation-promoting composition, but can be applied as a functional structure capable of controlling the degradation of polymer-based implantable devices. More specifically, the composite can be manufactured in the form of particles ranging from tens of nanometers to several micrometers, which can be mixed or embedded within a biodegradable or non-biodegradable polymer matrix and included as part of a polymer structure implanted in the body.

[0045] This composition is particularly useful for devices that are required to disappear after performing a function within the body for a certain period, such as tissue regeneration scaffolds, nerve guide tubes, biodegradable implants, and drug delivery devices. After applying a polymer insert containing the composite into the body, the user can selectively induce the degradation of the polymer structure by applying near-infrared (NIR) and ultrasound from the outside at a desired time.

[0046] Ultrasonic stimulation induces direct cleavage of polymer chains through the decomposition of radical-generating substances (such as AIPH) contained in the core, and NIR stimulation accelerates the decomposition rate through the exothermic reaction of photothermal conversion carrier shell materials (such as MIL-100 (Fe), polydopamine, etc.) while simultaneously promoting radical generation. All of these mechanisms of action can be controlled to proceed at a temperature range of approximately 36 to 40 degrees Celsius, which does not cause tissue damage.

[0047] Below, the contents of the present invention will be further explained along with specific embodiments.

[0048]

[0049] (Example 1)

[0050] In Example 1, AIPH (2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride) was used as the core material to generate radicals in response to ultrasound, and MIL-100 (Fe) was used as the shell material to generate heat in response to NIR (near-infrared radiation) as the carrier material.

[0051] Figure 1 shows a schematic diagram of the design of AIPH@MIL-100, in which AIPH is loaded inside a MIL-100 (Fe) carrier. These loaded particles are embedded in a polymer matrix during the synthesis of a polymer film to be inserted into the body and are processed into a film form.

[0052] When ultrasound is applied to the finished polymer film, AIPH inside the MIL-100(Fe) carrier is released, generating alkyl radicals that cut the polymer chains.

[0053] In addition, NIR penetrable into the body (808nm / 2.0 W / cm²) 2 When ) is applied, a local temperature rise occurs due to the photothermal effect of MIL-100(Fe), which accelerates the polymer decomposition rate.

[0054] The technology according to the embodiment of the present invention presents an innovative biodegradation promotion method that accelerates the in vivo degradation of polymer films in a non-invasive manner utilizing ultrasound and NIR.

[0055] Figure 2 illustrates the verification of radical generation and photothermal reaction effects of the polymer degradation-promoting material. First, AIPH@MIL-100 was dispersed in oxygen-free water, and changes in dissolved oxygen concentration were measured upon application of ultrasound, confirming the occurrence of radical generation. Additionally, when the polymer film was inserted into a rat and irradiated with NIR, a localized temperature rise was observed, demonstrating the exothermic effect caused by photothermal activity. Furthermore, the degree of biodegradation was evaluated by applying ultrasound and NIR to a PLLA (Poly(L-lactic acid)) polymer film embedded with AIPH@MIL-100. The experimental conditions involved ultrasound (low-frequency ultrasound in the range of 20 kHz to 200 kHz was used, with an intensity of 1 W / cm² considering human safety). 2 Up to 3W / cm 2 Set to) 10 min, NIR (808nm laser at 2W / cm² 2 (Authorized as such) 30 minutes was used as one set, and this process was repeated a total of 4 times. As a result, it was confirmed by weight loss that PLLA was completely degraded in a total of 160 minutes, which indicates that the degradation rate was accelerated very effectively compared to Pristine PLLA, which generally has a biodegradation period of more than one year. In Figure 2, (a) shows the verification of the activation of the biodegradation acceleration mechanism, and (b) shows the verification of the biodegradation rate, thereby proving the excellent polymer degradation promoting effect of the present invention.

[0056] The present invention provides a technical means to safely and effectively induce the degradation of bio-implantable polymer structures and possesses high scalability and technological impact applicable to various biomedical fields, such as polymer-based tissue regeneration implants, biodegradable nerve guide tubes, and drug delivery systems.

[0057] Although the present invention has been described above with reference to preferred embodiments, those skilled in the art will understand that various modifications and changes can be made to the invention without departing from the spirit and scope of the invention as set forth in the following claims.

Claims

1. As a radical and photothermal reaction-inducing polymer degradation composite having a core-shell structure, A core comprising a radical-generating material that cleaves polymer chains; and A shell comprising a photothermal conversion carrier material that promotes polymer chain cleavage through heat generation by near-infrared irradiation, Radical and photothermal reaction-induced polymer decomposition complex.

2. In Paragraph 1, The above radical-generating substance generates radicals by the application of ultrasound, Radical and photothermal reaction-induced polymer decomposition complex.

3. In Paragraph 2, The above radical-generating substance comprises one or more of AIPH (2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride), 4,4'-azobis(4-cyanopentanoic acid), BaTiO3, curcumin, methylene blue, and indocyanine green, Radical and photothermal reaction-induced polymer decomposition complex.

4. In Paragraph 1, The above photothermal conversion carrier material comprises a metal-organic framework (MOF) material, MXene, polydopamine, or gold nanocages, Radical and photothermal reaction-induced polymer decomposition complex.

5. In Paragraph 4, The above MOF material comprises MIL-100(Fe) or MIL-101(Fe), Radical and photothermal reaction-induced polymer decomposition complex.

6. In Paragraph 1, The above photothermal conversion carrier material generates heat upon application of near-infrared (NIR), Radical and photothermal reaction-induced polymer decomposition complex.

7. In Paragraph 6, When the photothermal conversion carrier material generates heat due to the above near-infrared rays, the wavelength and intensity of the light are adjusted so as not to affect the body, thereby controlling the heat generation temperature to be between approximately 36°C and 40°C. Radical and photothermal reaction-induced polymer decomposition complex.

8. In Paragraph 7, The wavelength of the light is 700 to 850 nm, Radical and photothermal reaction-induced polymer decomposition complex.

9. In Paragraph 7, The above light intensity is 0.5 to 2.0 W / cm 2 person Radical and photothermal reaction-induced polymer decomposition complex.

10. A polymer-based implantable device comprising a radical and photothermal reaction-inducing polymer decomposition composite according to any one of claims 1 to 9, The above-mentioned polymer-based implantable device performs its function within the body for a certain period and is capable of degrading the polymer by the application of near-infrared rays and ultrasound. Polymer-based implantable device.

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