Novel organic photothermal agents for photothermal therapy and compositions containing the same

Abstract

This invention relates to a novel organic photothermal agent for photothermal therapy and a composition containing the same. [Solution] The objective is to provide an organic photothermal agent represented by the following chemical formula (1) and a composition containing the same. JPEG2026121297000021.jpg5882 (Chemical formula (1) is as defined in claim 1)

Description

Technical Field

[0001] The present invention relates to an organic photothermal agent for photothermal therapy and a composition containing the same according to an embodiment of the present invention.

Background Art

[0002] Early diagnosis and accurate treatment of cancer reduce the risk of recurrence and provide potential for its treatment. Therefore, the development of highly efficient cancer treatment substances that can target cancer cell sites and effectively treat them is essential. Conventional cancer treatment methods such as chemotherapy, radiotherapy, and surgical treatment cause side effects such as tumor recurrence and damage to normal cells. One of the treatment methods to overcome this is photothermal therapy.

[0003] Photothermal therapy is a non-invasive (or minimally invasive) treatment method that uses a photothermal agent to convert light energy into heat and induce cancer cell death. Different from existing treatment methods, it can minimize damage to surrounding normal cells, and thus is attracting attention as a promising treatment method with few side effects. In order to design a photothermal agent with high photothermal conversion efficiency, the light energy absorbed by the photothermal agent must be efficiently released as thermal energy through a non-equilibrium relaxation process, and intramolecular vibration and rotational motion are involved in the release of thermal energy. Furthermore, although inorganic photothermal agents such as gold nanoparticles have excellent photothermal conversion efficiency and photostability, they have limitations in clinical application due to low biodegradability and long-term toxicity. In order to overcome such limitations, the development of highly efficient organic photothermal agents with excellent biocompatibility and optical properties is required.

Summary of the Invention

Problems to be Solved by the Invention

[0004] In order to solve the above-described problems, the present invention provides a novel coumarin-based organic photothermal agent for providing a photothermal effect with improved photothermal conversion efficiency and / or treatment efficiency (i.e., photothermal therapy) through new molecular design.

[0005] The present invention provides a composition containing an organic photothermal agent according to an embodiment of the present invention and applicable to photothermal therapy of cancer or tumor cells.

[0006] However, the problems to be solved by the present invention are not limited to those mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

Means for Solving the Problems

[0007] The organic photothermal agent according to one embodiment can be represented by the following chemical formula (1). [Chemical formula (1)]

[0008]

Chem.

[0009] (Here, each R<00001​​​​​​​​​​​​​​​​​​​​​​​​​ According to one embodiment, the chemical formula (1) can be selected from the following chemical formula (1-1). [Chemical formula (1-1)]

[0013] [Chemical structure]

[0014] (Here, each R 1 and R 2 is selected from hydrogen, a linear or branched alkyl group having 1 to 5 carbon atoms)

[0015] According to one embodiment, the chemical formula (1) can be selected from the following chemical formula (1-2). [Chemical formula (1-2)]

[0016] [Chemical structure]

[0017] (Here, each R 1 and R 2 is selected from hydrogen, a linear or branched alkyl group having 1 to 5 carbon atoms, and R 6 is selected from a halogenated alkyl group having 1 to 3 carbon atoms)

[0018] According to one embodiment, the halogenated alkyl may be a perfluoroalkyl group.

[0019] According to one embodiment, the organic photothermal agent can provide a photothermal effect under laser irradiation with a wavelength of 650 nm to 700 nm.

[0020] According to one embodiment, the organic photothermal agent can provide a photothermal effect under laser irradiation with an energy of 0.6 W / cm 2 to 1.0 W / cm 2 .

[0021] In one embodiment, the organic photothermal agent can be used in photothermal therapy.

[0022] A composition according to one embodiment is a pharmaceutical composition for the treatment of tumors or cancer, comprising an organic photothermal agent; and a carrier; according to claim 1 of an embodiment of the present invention.

[0023] In one embodiment, the organic photothermal agent may include the following chemical formulas (1-1) and (1-2). [Chemical formula (1-1)]

[0024] [ka]

[0025] (Here, R1 and R 2 (Selected from hydrogen, linear or branched alkyl groups with 1 to 5 carbon atoms) [Chemical formula (1-2)]

[0026] [ka]

[0027] (Here, each R 1 and R 2 R is selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms, 6 (Selected from alkyl halogens having 1 to 3 carbon atoms)

[0028] In one embodiment, the ratio of chemical formula (1-1) to chemical formula (1-2) may be 99:1 to 1:99 (w / w).

[0029] In one embodiment, the composition can provide a photothermal effect upon laser irradiation with a wavelength of 650 nm to 700 nm.

[0030] In one embodiment, the composition is 0.6 W / cm². 2 ~1.0W / cm 2Laser irradiation of energy can provide a photothermal effect.

[0031] In one embodiment, the composition can be used in photothermal therapy for cancer or tumors. [Effects of the Invention]

[0032] The present invention can provide a novel coumarin-based organic photothermal agent for high-efficiency organic photothermal agents with improved photothermal conversion efficiency.

[0033] This invention provides a novel coumarin-based organic photothermal agent applicable to photothermal therapy and pharmaceutical applications utilizing the same. [Brief explanation of the drawing]

[0034] [Figure 1] In one embodiment, the absorption and fluorescence spectra of the organic photothermal agent synthesized in the embodiment are shown, specifically (a) the absorption and fluorescence spectra of Cou, CouR, ICou, and ICouR (10 μM) in THF and (b) THF / PBS buffer (1 / 99).

[0035] [Figure 2] One embodiment evaluates the photothermal performance of the organic photothermal materials (ICou and ICouR) synthesized in the embodiment, showing the temperature change with respect to laser power density and concentration.

[0036] [Figure 3] One embodiment shows the 1H-NMR (a) and Mass (b) results of the organic photothermal agent (ICou) produced in the embodiment.

[0037] [Figure 4] One embodiment shows the 1H-NMR (a) and Mass (b) results of the organic photothermal agent (ICouR) produced in the embodiment. [Modes for carrying out the invention]

[0038] Embodiments of the present invention will be described in detail below with reference to the attached drawings. In the description of the present invention, if a specific description of a relevant known function or configuration is deemed to unnecessarily obscure the gist of the invention, such detailed description will be omitted. Furthermore, the terms used herein are those used to appropriately express preferred embodiments of the present invention, and these may vary depending on the intent of the user, operator, or the conventions of the art to which the invention belongs. Accordingly, the definitions of these terms must be based on the overall content of this specification.

[0039] Throughout the specification, when any member is located "on top of" another member, this includes not only cases where one member is in contact with another member, but also cases where there is an additional member between the two members.

[0040] Whenever a part of the specification "includes" any component, this does not mean that it excludes other components, but rather that it may include other components.

[0041] The coumarin-based organic photothermal agent of the present invention and its applications will be described in detail below with reference to embodiments and drawings. However, the present invention is not limited to such embodiments and drawings.

[0042] In one embodiment, the coumarin-based organic photothermal agent of the present invention may be a compound represented by the following chemical formula (1). The organic photothermal agent is a novel organic photothermal agent into which a receptor having strong stretching vibration (e.g., 1,3-bis(dicyanomethylidene)indan) is introduced, and a functional group that can be used as a free-rotating rotor (i.e., an alkyl halogenated group) (e.g., a -CF3 rotor) can be further introduced into the coumarin ring. That is, the organic photothermal agent is a highly efficient organic photothermal agent and can provide photophysical chemical properties that can be applied not only to photothermal therapy but also as a fluorescent probe (e.g., cancer cell targeting or fluorescence imaging). [Chemical formula (1)]

[0043] [ka]

[0044] In one embodiment, in the chemical formula (1), each R 1 ~R 6 R can be selected from hydrogen, halogens, linear or branched C1-C10 alkyl groups; C2-C10 alkenyl groups; C2-C10 alkynyl groups; and C1-C10 halogenated alkyl groups. Preferably, each R 1 ~R 6 R can be selected from hydrogen and linear or branched alkyl groups having 1 to 10 carbon atoms, and halogenated alkyl groups having 1 to 10 carbon atoms. More preferably, R can be selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms, and halogenated alkyl groups having 1 to 5 carbon atoms, and even more preferably, each R 1 ~R 2 R is selected from linear or branched alkyl groups having 1 to 5 carbon atoms. 3 ~R 6 The halogenated alkyl group can be selected from hydrogen and a branched chain of 1 to 5 carbon atoms. For example, the halogenated alkyl group may be a perfluoroalkyl group, and may be -CF3, -CF2CF3, or -CF2CF2CF3.

[0045] In one embodiment, the chemical formula (1) can be selected from the following chemical formulas (1-1). [Chemical formula (1-1)]

[0046] [ka]

[0047] In the above chemical formula (1-1), each of the R 1 and R 2 This can be selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms. Preferably, it may be a linear or branched alkyl group having 1 to 5 carbon atoms.

[0048] In one embodiment, the chemical formula (1) can be selected from the following chemical formulas (1-2). [Chemical formula (1-2)]

[0049] [ka]

[0050] In the above chemical formula (1-2), each R 1 and R 2 R is selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms, 6 The alkyl halide can be selected from C1-C3 alkyl halides. The alkyl halide may also be a perfluoroalkyl group. Preferably, each R 1 and R 2 This may be a linear or branched alkyl group having 1 to 5 carbon atoms.

[0051] In one embodiment, the organic photothermal agent incorporates a receptor (1,3-bis(dicyanomethylidene)indan) with strong stretching vibrations in the coumarin molecule to release the energy of electrons excited by light into the form of heat, and further incorporates a free-rotating rotor (i.e., an alkyl halogenate) (e.g., a -CF3 rotor) to enhance photothermal conversion efficiency. Furthermore, the strong electron-accepting ability of the receptor shifts the light absorption of coumarin from its existing short wavelengths to the near-infrared region, and light in the near-infrared region is effective for photothermal therapy due to its lower energy and deeper cell penetration than light in the visible light region. For example, the organic photothermal agent of chemical formula (1-2) contains a receptor with stretching vibrations and a free-rotating rotor, so that irradiated light can be efficiently converted into thermal energy, improving photothermal conversion efficiency (e.g., 50% or more; 58% or more; 60% or more; 70% or more). In addition, the strong electron-accepting ability of the receptor shifts the light absorption of coumarin from its existing short wavelengths to the near-infrared region. This is because light in the near-infrared region has lower energy and deeper cell penetration than light in the visible light region, making it more advantageous and suitable for photothermal therapy. This expands its range of applications not only as a fluorescent probe based on conventional coumarin dyes, but also as a photothermal agent.

[0052] In one embodiment, the organic photothermal agent can be used in photothermal therapy (PTT) in vivo or in vitro. In one embodiment, the organic photothermal agent can be irradiated with a laser of wavelengths of 4,000 nm to 700 nm; 500 nm to 700 nm; or 600 nm to 700 nm and energy of 0.1 W / cm² to 1 W / cm² to provide therapeutic effects (e.g., anti-cancer treatment) through photothermal therapy. For example, the organic photothermal agent can be used in photothermal therapy by generating heat of 20°C or higher; 30°C or higher; 50°C or higher; or 60°C or higher when irradiated with a light source.

[0053] In other words, the organic photothermal agent can further incorporate a receptor (1,3-bis(dicyanomethylidene)indan) having strong stretching vibrations to release the energy of electrons excited by light into the form of heat, and a free-rotating rotor (e.g., a -CF3 rotor), thereby providing a highly efficient photothermal effect by laser irradiation.

[0054] In one embodiment, the photothermal therapy of the organic photothermal agent enables photothermal treatment that induces cell death in cancer cells (e.g., HeLa cells) at a temperature-dependent rate due to photon absorption.

[0055] In one embodiment, the organic photothermal agent is utilized as a fluorescent probe upon light irradiation, which can be used in vivo or in vitro for cell targeting (for example, by targeting cancer cells to generate a fluorescent signal) or cell fluorescence imaging.

[0056] In one embodiment, the composition may include the compound represented by chemical formula (1), a salt thereof, or both, as the organic photothermal agent; and a pharmaceutically acceptable carrier.

[0057] In one embodiment, the composition can provide cell death or therapeutic effects in vivo or in vitro through photothermal effects via light irradiation from a light source. Alternatively, it can be used in vivo or in vitro for cell targeting (for example, by targeting cancer cells to generate a fluorescent signal) or cell fluorescence imaging.

[0058] In one embodiment, the salt may be derived from an inorganic or organic acid and a base, and may be a pharmaceutically acceptable salt. The inorganic and organic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonate, ethanesulfonic acid, formic acid, benzoic acid, malonic acid, sulfonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like.

[0059] In one embodiment, the carrier can be applied without limitation as long as it is a pharmaceutically acceptable carrier component, and can be appropriately selected depending on the method of use of the composition (e.g., administration or infusion), the formulation of the desired composition, the function of the composition, etc. For example, the carrier may always contain water or an organic solvent.

[0060] Depending on the embodiment, the composition may contain, as a pharmaceutically active ingredient, the compound represented by chemical formula (1), a salt thereof, or both, as an organic pyrotherm, in amounts exceeding 0% to 99%, 0.0001% to 99%, or 0.001% to 99%. For example, 1 × 10 -5 M (moles) or more, preferably 1 × 10⁻⁶ -5 M (moles) ~ 1 × 10⁻⁶ -2 M (moles), more preferably 1 × 10⁻⁶ -4 M (moles) ~ 1 × 10⁻⁶ -2 It may be included as a concentration of M (moles).

[0061] In one embodiment, the composition may contain an organic photothermal agent comprising chemical formula (1-1), chemical formula (1-2), or both thereof. That is, when two or more organic photothermal agents are included, the mixing ratio (w / w) of one organic photothermal agent to the remaining organic photothermal agents may be 99:1 to 1:99 (w / w); 90:10 to 10:90 (w / w); 80:20 to 20:80 (w / w); or 40:60 to 50:50 (w / w). For example, the ratio of chemical formula (1-1) and chemical formula (1-2) may be 99:1 to 1:99 (w / w); 90:10 to 10:90 (w / w); 80:20 to 20:80 (w / w); or 40:60 to 50:50 (w / w).

[0062] In one embodiment, the pH of the composition is 7-8, which can be adjusted with a buffer solution.

[0063] In one embodiment, the composition can be applied as a powder, gel, emulsion, liquid phase, or molded part. For example, the composition can be coated or impregnated onto a support such as an analytical chip, semiconductor chip, electrical circuit, fiber, pulp, polymer film, or glass substrate.

[0064] In one embodiment, the organic photothermal agent or composition may be used in photothermal therapy (i.e., photothermal treatment) to remove or reduce cancer cells or tumor cells by photothermal development that occurs when a photon light source is irradiated in vivo or in vivo. The photothermal therapy is used to treat diseases, conditions, or disorders related to cancer cells, tumor cells, or overproliferating cells, and is applied to, but is not limited to, cancer treatment or tumor reduction, such as head and neck cancer, breast cancer, uterine cancer, lung cancer, bladder cancer, colon cancer, prostate cancer, glioma, esophageal cancer, gastric cancer, brain cancer, brain tumor, rectal cancer, colorectal cancer, skin cancer, ovarian cancer, cervical cancer, kidney cancer, hematological cancer, pancreatic cancer, testicular cancer, laryngeal cancer, oral cancer, thyroid cancer, liver cancer, osteosarcoma, bone tumor, leukemia, and lymphoma.

[0065] In one embodiment, the photothermal therapy method of the present invention includes the steps of bringing a composition or organic photothermal agent (for example, a compound represented by chemical formula (1)) according to the embodiment of the present invention into contact with cells to be treated; and irradiating the area of ​​cells that has been in contact with a light source.

[0066] In one embodiment, the step of contacting the target cells can be performed in vitro or intra vivo by administering or injecting the composition or organic photothermal agent (for example, the compound shown in chemical formula (1)) into the target cells. The target cells may be mammalian cells or cells of mammals other than humans.

[0067] In one embodiment, the step of irradiating with the light source can be used to kill, remove, or reduce target cells (e.g., cancer cells, tumor cells, or both) by the photothermal effect of the organic photothermal material.

[0068] In one embodiment, the step of irradiating with the light source may involve irradiating for 1 second or more; 1 minute or more; 5 minutes or more; 10 minutes or more; or 30 minutes to 1 hour.

[0069] In one embodiment, “treatment” means a set of actions (e.g., therapy) performed to alleviate and / or improve a disease, disorder and / or disorder of interest. For example, “treatment” includes, but is not limited to, activities that inhibit the generation and growth of cancer cells and / or tumors, or that improve the symptoms of cancer invasion, metastasis, and recurrence.

[0070] In one embodiment, “administration” means introducing the compound or composition of the present invention to a patient by any suitable method, and the route of administration of the compound or composition of the present invention may be any common route as long as it can reach the target tissue (or target cells). For example, such administration may be oral and / or parenteral, and more specifically, may be oral, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, intranasal, intrapulmonary, rectal, oral (including ophthalmic, oral mucosal, and sublingual) administration, intranasal, bronchial (inhalation) administration, topical, vaginal, intraperitoneal, and intradural administration, etc.

[0071] The invention will be described below with reference to preferred embodiments, but those skilled in the art will understand that the invention can be modified and altered in various ways without departing from the spirit and scope of the invention as described in the claims below. Embodiment

[0072] Synthesis process [Scheme 1]

[0073] [ka]

[0074] Combination of SCou and SCouR

[0075] According to Scheme 1, 7-(diethylamino)coumarin (or 7-(diethylamino)-4-(trifluoromethyl)coumarin) (1 eq.) and Lawesson's reagent (2 eq.) were dissolved in toluene and refluxed for 24 hours. After this time, the organic solvent was evaporated and the crude product was purified by column chromatography using silica gel.

[0076] Combination of ICou and ICouR

[0077] According to Scheme 1, SCou or SCouR (1 eq.), 1,3-bis(dicyanomethylidene)indan (1.2 eq.), and benzoyl chloride (1.1 eq.) were dissolved in toluene and stirred at room temperature for 24 hours. Then, triethylamine (2.5 eq.) was added. DCM was poured into the solution and the solution was washed with distilled water. The separated organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography using silica gel.

[0078] The 1H-NMR (Figure 3(a)) and HR-MS (Figure 3(b)) results for ICou are shown in Figure 3.

[0079] The 1H-NMR (Figure 4(a)) and HR-MS (Figure 4(b)) results of ICouR are shown in Figure 4. Physical property evaluation

[0080] The absorption and fluorescence spectra of ICou and ICouR were irradiated with THF and 99% PBS. Referring to Figure 1a, the maximum absorption wavelengths of ICou and ICouR were observed at 370 nm and 395 nm, respectively. The introduction of the strong electron-withdrawing group 1,3-bis(dicyanomethylidene)indane resulted in redshifted maximum absorption wavelengths of 590 nm and 602 nm, respectively. Compared to ICouR under THF, ICouR under 99% PBS showed a considerably redshifted maximum absorption wavelength (650 nm), suggesting that ICouR formed a typical J-aggregate that extends into the NIR region (Figure 1(b)).

[0081] 690nm, 0.8W / cm 2 Under laser irradiation, the reaction was dependent on the ICouR concentration (10-40 μM), and the reaction was controlled by increasing the aqueous solution temperature during irradiation. For a 10 μM ICouR, the laser intensity was 0.6-1.0 W / cm². 2 The temperature increase of the aqueous solution was investigated in a dependent manner.

[0082] Figure 1 shows the absorption and fluorescence spectra of Cou, CouR, ICou, and ICouR (10 μM) in (a) THF and (b) THF / PBS buffer (1 / 99).

[0083] The photothermal performance of ICou and ICouR using a 690nm laser was evaluated. Figures 2(a) to (d) show the relationship between the temperature change and concentration of ICou and ICouR solutions and the power density of the 690nm laser, demonstrating that temperature is positively correlated with PA concentration and laser power density. The solution temperature of ICou and ICouR (20 μM) was measured with a 690nm laser (0.8 W / cm²). -2During continuous irradiation with ), the ROS generation capacity increased, inducing temperature increases of 19°C and 35°C, respectively, after 6 minutes of irradiation. As a result, a high photothermal conversion efficiency of 58% was observed (Figure 2(e)). In addition, the ROS generation capacity of ICou and ICouR was irradiated (Figure 2(f)). DCFH (2,7-Dichlorodihydrofluorescein) was selected and the total ROS was measured. In the presence of ICou and ICouR, the emission intensity of DCFH increased by approximately 125 times after 150 seconds of irradiation, showing superior ROS generation capacity compared to the commercially available photosensitizer MB (photosensitizer methylene blue).

[0084] Figure 2 shows the results of 690nm laser irradiation (0.8W / cm²). -2 (a) shows the concentration-dependent photothermal heating curves of (ICou) and (b) ICouR aqueous solutions under 690 nm laser irradiation. (c) shows the power density-dependent photothermal heating curves of (ICou) and (d) ICouR aqueous solutions (20 μM) under 690 nm laser irradiation (0.8 W / cm⁻²). (e) shows the photothermal heating and cooling curves of ICouR aqueous solution (20 μM) under 690 nm laser irradiation (0.8 W / cm⁻²) and a linear fitting of the cooling time to -ln(θ). (f) shows the relative PL intensity (I / I⁻¹) of DCFH (10 μM) when 1 μM MB, ICou, and ICouR are present in the aqueous solution, at 0.8 W / cm⁻¹. -2 The sample was irradiated with a 690nm laser for different durations. Specifically, in Figure 2, it can be seen that the temperature of the ICouR aqueous solution increases depending on the concentration of ICouR and the intensity of the laser.

[0085] The present invention provides a novel coumarin-based organic photothermal agent that is highly efficient. In particular, when an aqueous solution of the synthesized organic photothermal agent ICouR is irradiated with a 690 nm laser, the rise in the aqueous solution temperature suggests that ICouR is applicable to photothermal therapy. Furthermore, it was confirmed that the temperature of the ICouR aqueous solution increases in a dependent manner with the concentration of ICouR and the intensity of the laser. Therefore, the coumarin-based organic photothermal agent of the present invention is suitable for designing a highly efficient organic photothermal agent applicable to photothermal therapy by introducing stretching vibration receptors and free-rotating rotors to the coumarin molecule.

[0086] As described above, although embodiments have been described by limited embodiments and figures, a person with ordinary skill in the art can make various modifications and variations from the above description. For example, the described techniques may be performed in a different order than described, and / or the described components may be combined or combined in a different manner than described, or substituted or replaced by other components or equivalents, and still achieve appropriate results. Accordingly, the scope of the present invention is not limited to the disclosed embodiments, but is defined by the claims and equivalents thereof.

[0087] (Note) (Note 1) An organic photothermal agent represented by the chemical formula (1) below. [Chemical formula (1)] [ka] (Here, each R 1 ~R 6 (Selected from hydrogen, halogens, linear or branched alkyl groups having 1 to 10 carbon atoms; alkenyl groups having 2 to 10 carbon atoms; alkynyl groups having 2 to 10 carbon atoms; and halogenated alkyl groups having 1 to 10 carbon atoms)

[0088] (Note 2) In the above chemical formula (1), each R 1 ~R 6 The organic photothermal agent described in Appendix 1 is selected from hydrogen, halogens, linear or branched alkyl groups having 1 to 5 carbon atoms; alkenyl groups having 2 to 5 carbon atoms; alkynyl groups having 2 to 5 carbon atoms; and halogenated alkyl groups having 1 to 5 carbon atoms.

[0089] (Note 3) In the above chemical formula (1), each R 1 ~R 2 It is selected from hydrogen and linear or branched alkyl groups having 1 to 5 carbon atoms. In the above chemical formula (1), each R 3~R 6 The organic photothermal agent described in Appendix 1 is selected from hydrogen and halogenated alkyl groups having 1 to 5 carbon atoms.

[0090] (Note 4) The aforementioned chemical formula (1) is an organic photothermal agent as described in Appendix 1, selected from the following chemical formulas (1-1). [Chemical formula (1-1)] [ka] (Here, each R 1 and R 2 (Selected from hydrogen, linear or branched alkyl groups with 1 to 5 carbon atoms)

[0091] (Note 5) The aforementioned chemical formula (1) is selected from the following chemical formulas (1-2), and is an organic photothermal agent as described in Appendix 1. [Chemical formula (1-2)] [ka] (Here, each R 1 and R 2 R is selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms, 6 (Selected from alkyl halogens having 1 to 3 carbon atoms)

[0092] (Note 6) The aforementioned alkyl halogen is a perfluoroalkyl group, as described in Appendix 1, an organic photothermal agent.

[0093] (Note 7) The organic photothermal agent described above provides a photothermal effect when irradiated with a laser at a wavelength of 650 nm to 700 nm, as described in Appendix 1.

[0094] (Note 8) The aforementioned organic photothermal agent has a load capacity of 0.6 W / cm². 2 ~1.0W / cm 2 An organic photothermal agent described in Appendix 1 that provides a photothermal effect through laser irradiation of energy.

[0095] (Note 9) The aforementioned organic photothermal agent is used in photothermal therapy, as described in Appendix 1.

[0096] (Note 10) The organic photothermal agent described in Appendix 1, Carrier and A composition for the treatment of tumors or cancer, comprising:

[0097] (Note 11) The aforementioned organic heat-generating agent is the composition described in Appendix 10, comprising the following chemical formulas (1-1) and (1-2). [Chemical formula (1-1)] [ka] (Here, each R 1 and R 2 (Selected from hydrogen, linear or branched alkyl groups with 1 to 5 carbon atoms) [Chemical formula (1-2)] [ka] (Here, each R 1 and R 2 R is selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms, 6 (Selected from alkyl halogens having 1 to 3 carbon atoms)

[0098] (Note 12) The composition as described in Appendix 11, wherein the ratio of chemical formula (1-1) and chemical formula (1-2) is 99:1 to 1:99 (w / w).

[0099] (Note 13) The composition described above provides a photothermal effect upon laser irradiation at a wavelength of 650 nm to 700 nm, as described in Appendix 10.

[0100] (Note 14) The composition has a concentration of 0.6 W / cm². 2 ~1.0W / cm 2The composition described in Appendix 10, which provides a photothermal effect by laser irradiation of energy.

[0101] (Note 15) The composition described above is used in photothermal therapy for cancer or tumors, as described in Appendix 10.

Claims

1. An organic photothermal agent represented by the chemical formula (1) below. [Chemical formula (1)] 【Chemistry 1】 (Here, each R １ ~R ６ (Selected from hydrogen, halogens, linear or branched alkyl groups having 1 to 10 carbon atoms; alkenyl groups having 2 to 10 carbon atoms; alkynyl groups having 2 to 10 carbon atoms; and halogenated alkyl groups having 1 to 10 carbon atoms)

2. In the above chemical formula (1), each R １ ~R ６ The organic photothermal agent according to claim 1, wherein is selected from hydrogen, halogen, linear or branched alkyl groups having 1 to 5 carbon atoms; alkenyl groups having 2 to 5 carbon atoms; alkynyl groups having 2 to 5 carbon atoms; and halogenated alkyl groups having 1 to 5 carbon atoms.

3. In the above chemical formula (1), each R １ ~R ２ It is selected from hydrogen and linear or branched alkyl groups having 1 to 5 carbon atoms. In the above chemical formula (1), each R ３ ~R ６ The organic photothermal agent according to claim 1, wherein is selected from hydrogen and a halogenated alkyl group having 1 to 5 carbon atoms.

4. The organic photothermal agent according to claim 1, wherein the chemical formula (1) is selected from the following chemical formulas (1-1). [Chemical formula (1-1)] 【Chemistry 2】 (Here, each R １ and R ２ is selected from hydrogen, a linear or branched alkyl group having 1 to 5 carbon atoms)

5. The organic photothermal agent according to claim 1, wherein the chemical formula (1) is selected from the following chemical formulas (1-2). [Chemical formula (1-2)] 【Transformation 3】 (Here, each R １ and R ２ R is selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms, ６ (Selected from halogenated alkyl groups having 1 to 3 carbon atoms)

6. The organic photothermal agent according to claim 1, wherein the alkyl halogen is a perfluoroalkyl group.

7. The organic photothermal agent according to claim 1, wherein the organic photothermal agent provides a photothermal effect when irradiated with a laser at a wavelength of 650 nm to 700 nm.

8. The aforementioned organic light-heating agent has a load of 0.6 W / cm². ２ ~1.0 W / cm ２ The organic photothermal agent according to claim 1, which provides a photothermal effect by laser irradiation of energy.

9. The organic photothermal agent is used in photothermal therapy, as described in claim 1.

10. The organic photothermal agent according to claim 1, Carrier and A composition for the treatment of tumors or cancer, comprising:

11. The composition according to claim 10, wherein the organic heat-generating agent comprises the following chemical formulas (1-1) and (1-2). [Chemical formula (1-1)] 【Chemistry 4】 (Here, each R １ and R ２ (Selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms) [Chemical formula (1-2)] 【Transformation 5】 (Here, each R １ and R ２ R is selected from hydrogen, linear or branched alkyl groups having 1 to 5 carbon atoms, ６ (Selected from halogenated alkyl groups having 1 to 3 carbon atoms)

12. The composition according to claim 11, wherein the ratio of chemical formula (1-1) and chemical formula (1-2) is 99:1 to 1:99 (w / w).

13. The composition according to claim 10, wherein the composition provides a photothermal effect upon laser irradiation with a wavelength of 650 nm to 700 nm.

14. The aforementioned composition has a concentration of 0.6 W / cm². ２ ~1.0 W / cm ２ The composition according to claim 10, which provides a photothermal effect by laser irradiation of energy.

15. The composition according to claim 10, which is used in photothermal therapy for cancer or tumors.

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