Compositions containing 5-aminolevulinic acid hydrochloride

JP7629525B2Active Publication Date: 2025-02-13キムジンワン +3
View PDF 10 Cites 0 Cited by

Patent Information

Application Number
JP2023527369
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2021-07-19
Filing Date
2021-10-25
Publication Date
2025-02-13
Estimated Expiration
2041-10-25

AI Technical Summary

Benefits of technology

【0022】 発明による5‐アミノレブリン酸塩酸塩を含む組成物は、光疫学治療法(photo dynamic therapy:PDT)に使われる物質である5‐アミノレブリン酸塩酸塩を含んで蛍光誘導悪性組織視覚化経口用薬物組成物として利用したり、ニキビ肌改善用化粧料組成物として使用することができる。

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure 0007629525000010
    Figure 0007629525000010
  • Figure 0007629525000011
    Figure 0007629525000011
  • Figure 0007629525000012
    Figure 0007629525000012
Patent Text Reader

Abstract

The present invention provides a composition containing 5-aminolevulinic acid hydrochloride, characterized by comprising 5-aminolevulinic acid hydrochloride, fermented Baasob extract, Cordyceps sinensis extract, Kuril shrimp oil, sodium polydeoxyribonucleotide, propylene glycol, hyaluronidase, L-carnitine, caffeine, Origanum vulgare leaf oil, ascorbic acid (Vitamin C), allantoin, cetyl alcohol, and mineral water.
Need to check novelty before this filing date? Find Prior Art

Description

[Technical field]

[0001] The present invention relates to a composition containing 5-aminolevulinic acid hydrochloride, and more particularly, to a composition containing 5-aminolevulinic acid hydrochloride, which is a substance used in photodynamic therapy (PDT), and can be used as an oral pharmaceutical composition for fluorescence-induced visualization of malignant tissue, or as a cosmetic composition for improving acne-prone skin.

[0002] The present invention also relates to a composition comprising 5-aminolevulinic acid hydrochloride, and more particularly, to a composition comprising 5-aminolevulinic acid hydrochloride, which is a substance used in photodynamic therapy and diagnosis (PDT&PDD), and is used as a fluorescence-induced malignant tissue visualization oral pharmaceutical composition, which accumulates in cancer cells or cancer tissues and exhibits fluorescence or phosphorescence, and can be used for early diagnosis of tumors, thereby maximizing the efficiency of cancer diagnosis and treatment. [Background technology]

[0003] Photodynamic therapy (PDT) is a technology that uses photo-sensitizers to treat intractable diseases such as cancer and acne without surgery. PDT has been actively researched since the early 20th century, and is currently used in cancer diagnosis and treatment, allogeneic and autologous bone marrow transplantation, graft-versus-host reaction resolution by extracorporeal photopheresis, antibiotics, treatment of infectious diseases such as AIDS, organ and skin graft surgery, arthritis, spinal muscular atrophy, etc. PDT is also used to strengthen the immune system and control and regulate immune responses, and its range of applications is gradually expanding to include regenerative medicine, biosensors, and optogenetics.

[0004] In particular, PDT, which is used to treat cancer, is a treatment method that utilizes the principle that when a photosensitizer, a substance that reacts sensitively to light, is administered into the body, singlet oxygen or free radicals are generated by a chemical reaction between the abundant oxygen in the body and the external light when light is irradiated from outside, and this singlet oxygen or free radicals induces and destroys various lesions and cancer cells.

[0005] Currently, photosensitizers used in PDT therapy include porphyrin derivatives, chlorin, bacteriochlorin, phthalocyanine, 5-aminolevulinic acid derivatives, and porfimer sodium.

[0006] Cyclic tetrapyrrole derivatives as photosensitizers are not only selectively accumulated in cancer cells, but also show fluorescence or phosphorescence due to the characteristics of the compound, so they are also used as early tumor diagnosis reagents. In addition, metalloporphyrins, which have metals bound to the inside of cyclic tetrapyrrole, show various characteristics depending on the type of bound metal, so they are used as contrast agents in MRI (magnetic resonance imaging) to be applied to early diagnosis of tumor cells such as cancer cells. 5-aminolevulinic acid derivatives, which are the most well-known photosensitizers, have the advantages of being simple to use, having a small molecular weight, relatively easy to penetrate into the skin, and being safe with few side effects.

[0007] In addition, photoimmunotherapy has the advantage of being able to selectively remove only cancer cells while leaving normal cells intact. It also has the advantage of being easy to administer, as it can be performed with just simple local anesthesia, almost eliminating the risk of general anesthesia. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Korean Patent No. 10-1322259 (registered October 21, 2013) [Patent Document 2] Korean Patent No. 10-1638664 (registered on July 5, 2016) [Patent Document 3] Korean Patent No. 10-1135147 (registered on April 3, 2012) [Patent Document 4] Korean Patent No. 10-1622031 (registered on May 11, 2016) [Patent Document 5] Korean Patent No. 10-1659855 (registered on September 20, 2016) [Patent Document 6] Korean Patent No. 10-1183732 (registered on September 11, 2012) Summary of the Invention [Problem to be solved by the invention]

[0009] The present invention provides a composition containing 5-aminolevulinic acid hydrochloride, which is a substance used in photodynamic therapy (PDT), and can be used as an oral pharmaceutical composition for fluorescence-induced visualization of malignant tissue, or as a cosmetic composition for improving acne-prone skin.

[0010] In addition, the present invention provides a cosmetic composition containing 5-aminolevulinic acid hydrochloride, which is a substance used in photodynamic therapy (PDT), and which can effectively improve acne and other skin problems by minimizing skin irritation and suppressing inflammatory reactions occurring in skin tissues.

[0011] In addition, the present invention provides a composition containing 5-aminolevulinic acid hydrochloride, which is a substance used in photodynamic therapy and diagnosis (PDT&PDD), and is used as a fluorescence-induced malignant tissue visualization oral pharmaceutical composition, which accumulates in cancer cells or cancer tissues and exhibits fluorescence or phosphorescence, and can be used for early diagnosis of tumors, thereby maximizing the efficiency of cancer diagnosis and treatment.

[0012] The various problems that the present invention aims to solve 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 problem]

[0013] The composition containing 5-aminolevulinic acid hydrochloride according to the present invention is utilized as an oral pharmaceutical composition containing 5-aminolevulinic acid hydrochloride for fluorescence-induced malignant tissue visualization.

[0014] The 5-aminolevulinic acid hydrochloride is orally administered and absorbed, causing the tumor site to emit a fluorescent color, thereby enabling the tumor site to be distinguished from normal cell tissue. The fluorescent-induced malignant tissue visualization oral pharmaceutical composition containing 5-aminolevulinic acid hydrochloride is administered at 18 to 20 mg per patient's body weight, and in the case of surgery, it can be orally administered 2 to 4 hours before anesthesia induction.

[0015] By dissolving 1.5 g of the 5-aminolevulinic acid hydrochloride in 50 mL of purified water, a solution containing 5-aminolevulinic acid hydrochloride can be prepared so as to contain 30 mg of 5-aminolevulinic acid hydrochloride per mL.

[0016] In addition, the composition containing 5-aminolevulinic acid hydrochloride according to the present invention can be used to prepare a cosmetic composition for improving acne-prone skin by adding 5-aminolevulinic acid hydrochloride, fermented Baasob extract, Cordyceps sinensis extract, Kuril shrimp oil, sodium polydeoxyribonucleotide, propylene glycol, hyaluronidase, L-carnitine, caffeine, Origanum vulgare leaf oil, ascorbic acid (Vitamin C), allantoin, cetyl alcohol and mineral water.

[0017] The composition may contain 8 to 12% by weight of 5-aminolevulinic acid hydrochloride, 0.1 to 2.5% by weight of fermented Baasob extract, 1 to 3% by weight of Cordyceps sinensis extract, 0.5 to 1.5% by weight of Kuril shrimp oil, 1 to 2% by weight of sodium polydeoxyribonucleotide, 10 to 20% by weight of propylene glycol, 1 to 3% by weight of hyaluronidase, 3 to 5% by weight of L-carnitine, 2 to 4% by weight of caffeine, 0.1 to 1.0% by weight of Origanum Vulgare Leaf oil, 1 to 5% by weight of ascorbic acid (Vitamin C), 1 to 3% by weight of allantoin, 5 to 10% by weight of cetyl alcohol, and the remaining amount of mineral water.

[0018] The composition containing 5-aminolevulinic acid hydrochloride also contains 5-aminolevulinic acid hydrochloride, indole-3-acetic acid (IAA), polyethyleneimine, self-assembled ligand particles, purified water, a carrier, a glycerol fatty acid ester, and an emulsifier.

[0019] The weight ratio of the 5-aminolevulinic acid hydrochloride may be 30 to 50 parts by weight, indole-3-acetic acid (IAA) 10 to 20 parts by weight, polyethyleneimine 1 to 5 parts by weight, self-assembled ligand particle 5 to 15 parts by weight, purified water 10 to 20 parts by weight, carrier 10 to 20 parts by weight, glycerin fatty acid ester 20 to 30 parts by weight, and emulsifier 10 to 20 parts by weight.

[0020] The photoepidemiological treatment composition containing 5-aminolevulinic acid hydrochloride, indole-3-acetic acid (IAA), polyethyleneimine, self-assembled ligand particles, carrier, glycerol fatty acid ester, and emulsifier is orally administered to a patient at a dose of 35 mg / kg per body weight (kg), and then after 6 hours, light in the wavelength range of 660 to 680 nm can be irradiated to the tumor site of the patient to photoactivate the tumor in vivo.

[0021] Other embodiment details are included in the detailed description. Effect of the Invention

[0022] The composition containing 5-aminolevulinic acid hydrochloride according to the present invention can be used as an oral pharmaceutical composition for fluorescence-induced visualization of malignant tissues, including 5-aminolevulinic acid hydrochloride, a substance used in photodynamic therapy (PDT), or as a cosmetic composition for improving acne-prone skin.

[0023] In addition, the composition containing 5-aminolevulinic acid hydrochloride according to the present invention is a cosmetic composition containing 5-aminolevulinic acid hydrochloride, which is a substance used in photodynamic therapy (PDT), and can minimize skin irritation while suppressing inflammatory reactions occurring in skin tissues, thereby effectively improving acne-prone skin and other skin problems.

[0024] In addition, a composition containing 5-aminolevulinic acid hydrochloride, which is a substance used in photodynamic therapy and diagnosis (PDT&PDD), can be used as a fluorescence-induced malignant tissue visualization oral drug composition by being accumulated in cancer cells or cancer tissues and exhibiting fluorescence or phosphorescence, thereby enabling early diagnosis of tumors and maximizing the efficiency of cancer diagnosis and treatment.

[0025] It can be fully understood that the embodiments of the technical concept of the present invention can provide various effects that are not specifically mentioned. [Brief description of the drawings]

[0026] [Figure 1] 1 is a photograph showing the state where the site of a brain tumor of a patient emits fluorescence when a doctor performs surgery 6 hours after the patient ingests a composition containing 5-aminolevulinic acid hydrochloride according to the present invention. [Diagram 2] 1 is a graph showing the change in sebum secretion after applying cosmetic compositions for improving acne-prone skin according to Examples and Comparative Examples to the acne-prone skin of subjects for five days. [Figure 3a] 1 is a photograph showing the condition of acne-prone skin of a subject before using a cosmetic composition prepared according to an embodiment. [Figure 3b] 1 is a photograph showing the condition of acne-prone skin after a subject used a cosmetic composition prepared according to an embodiment once a day for 20 days. [Figure 4a] 1 is a photograph showing the condition of acne-prone skin of a subject before using a cosmetic composition prepared according to an embodiment. [Figure 4b] 1 is a photograph showing the condition of acne-prone skin after a subject used a cosmetic composition prepared according to an embodiment once a day for 20 days. [Figure 5a] 1 is a photograph showing the condition of acne-prone skin of a subject before using a cosmetic composition prepared according to an embodiment. [Figure 5b] 1 is a photograph showing the condition of acne-prone skin after a subject used a cosmetic composition prepared according to an embodiment once a day for 20 days. [Figure 6a] 1 is a photograph showing the condition of acne-prone skin of a subject before using a cosmetic composition prepared according to an embodiment. [Figure 6b] 1 is a photograph showing the condition of acne-prone skin after a subject used a cosmetic composition prepared according to an embodiment once a day for 20 days. [Figure 7a] 1 is a photograph showing the location of a brain tumor in a patient before the patient ingests the photoepidemiological treatment composition containing 5-aminolevulinic acid hydrochloride according to the present invention. [Figure 7b] 1 is a photograph showing the state in which the site of a patient's brain tumor emits fluorescence when a doctor performs surgery 6 hours after the patient ingests a photoepidemiological treatment composition containing 5-aminolevulinic acid hydrochloride according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] The advantages and features of the present invention, and the methods for achieving them, will become apparent from the following detailed description of the embodiments. However, the present invention is not limited to the embodiments described herein, and may be embodied in other forms. On the contrary, the embodiments described herein are provided so that the disclosure will be thorough and complete, and will fully convey the concept of the present invention to those skilled in the art.

[0028] The terms used in this application are merely used to describe specific embodiments and are not intended to limit the present invention. Singular expressions include plural expressions unless otherwise clearly indicated in the context.

[0029] Unless otherwise specified, all terms used herein, including technical and scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which this invention pertains. Terms, such as those commonly used and defined in dictionaries, should be interpreted as having a meaning consistent with the meaning that they have in the context of the relevant art, and should not be interpreted in an idealized or overly formal sense unless expressly defined in this application.

[0030] Hereinafter, the composition containing 5-aminolevulinic acid hydrochloride according to the present invention will be described in detail with reference to the accompanying drawings by way of preferred embodiments.

[0031] The composition containing 5-aminolevulinic acid hydrochloride according to one embodiment of the technical concept of the present invention can be an oral pharmaceutical composition for fluorescence-induced malignant tissue visualization.

[0032] That is, a composition containing 5-aminolevulinic acid hydrochloride according to one embodiment of the technical concept of the present invention can be used as an oral pharmaceutical composition for fluorescence-induced visualization of malignant tissue, containing 5-aminolevulinic acid hydrochloride, a substance used in photodynamic therapy (PDT).

[0033] After a patient drinks 5-aminolevulinic acid hydrochloride, the tumor site will emit a fluorescent color, so that the tumor site can be removed while protecting normal cell tissue as much as possible without being damaged during surgery.

[0034] 5-aminolevulinic acid hydrochloride is a substance that can be used in photodynamic therapy (PDT), which is a technology that uses photosensitizers (hereinafter referred to as photosensitizers) to treat intractable diseases such as cancer without surgery.

[0035] Photodiodeductal therapy (PDT) has been actively researched since the beginning of the 20th century, and is currently used in the diagnosis and treatment of cancer, allogeneic and autologous bone marrow transplants, resolution of graft-versus-host reaction through extracorporeal photopheresis, treatment of infectious diseases such as antibiotics and AIDS, organ and skin graft surgery, and treatment of arthritis and spinal muscular atrophy.

[0036] In addition, photodynamic therapy (PDT) is used to strengthen the immune system and control and regulate immune responses, and its range of applications is gradually expanding to include regenerative medicine, biosensors, and optogenetics.

[0037] In particular, PDT, which is used to treat cancer, is a treatment method that utilizes the principle that when a photosensitizer, a substance that reacts sensitively to light, is administered into the body, singlet oxygen or free radicals are generated through a chemical reaction between the abundant oxygen in the body and the external light when light is irradiated from outside, and this singlet oxygen or free radicals induces and destroys various lesions and cancer cells.

[0038] Photosensitizers currently used in PDT therapy include porphyrin derivatives, chlorin, bacteriochlorin, phthalocyanine, 5-aminolevulinic acid derivatives, and porfimer sodium.

[0039] 5-aminolevulinic acid hydrochloride is a C-5 aliphatic compound represented by the following formula 1, and is involved in the biosynthesis of tetrapyrrole (prophyrin, chlorophyll, heme, vitamin B) in various organisms. 12 It is one of the intermediate substances discovered in the process of synthesis, synthesis, etc.

[0040] [ka]

[0041] The composition containing 5-aminolevulinic acid hydrochloride according to the present invention can be administered at 18 to 20 mg of 5-aminolevulinic acid hydrochloride per patient's body weight, and the 5-aminolevulinic acid hydrochloride solution can be administered orally, and in the case of a patient undergoing surgery, it can be taken 2 to 4 hours before anesthesia induction.

[0042] FIG. 1 is a photograph showing the state in which the site of a brain tumor of a patient was emitting fluorescence when a doctor performed surgery 6 hours after the patient had taken the composition containing 5-aminolevulinic acid hydrochloride according to the present invention.

[0043] In other words, in the case of a patient undergoing surgery, 5-aminolevulinic acid hydrochloride was orally administered at 19 mg / kg per body weight (kg) three hours before inducing anesthesia. Six hours after ingestion, the doctor performed surgery, and the patient's brain tumor area glowed fluorescently in a photograph.

[0044] Referring to FIG. 1, when a patient drinks the composition containing 5-aminolevulinic acid hydrochloride according to the present invention and 6 hours later, when a doctor operates on the patient, the tumor site in the patient's brain emits a fluorescent color, so that normal cell tissues are not damaged or destroyed and only the cell tissues at the tumor site can be safely removed.

[0045] In addition, a composition containing 5-aminolevulinic acid hydrochloride according to the present invention can be prepared by dissolving 1.5 g of 5-aminolevulinic acid hydrochloride in 50 mL of purified water (pure water) so that the solution containing 5-aminolevulinic acid hydrochloride contains 30 mg of 5-aminolevulinic acid hydrochloride per mL.

[0046] The solution containing 5-aminolevulinic acid hydrochloride prepared as above may be a clear, colorless to slightly yellowish liquid.

[0047] As an example, the fluorescent induction malignant tissue visualization oral pharmaceutical composition containing 5-aminolevulinic acid hydrochloride according to one embodiment of the technical idea of ​​the present invention is prepared in a form that is orally administered and swallowed by patients. However, in addition to the oral administration form, the fluorescent induction malignant tissue visualization oral pharmaceutical composition containing 5-aminolevulinic acid hydrochloride according to the present invention can also be in the form of a patch that is applied to the skin of a patient, and can also be used for cosmetic purposes by adjusting the concentration of 5-aminolevulinic acid hydrochloride to less than 10%.

[0048] A composition containing 5-aminolevulinic acid hydrochloride according to another embodiment of the technical concept of the present invention may be a cosmetic composition for improving acne-prone skin.

[0049] That is, a composition containing 5-aminolevulinic acid hydrochloride according to another embodiment of the technical concept of the present invention contains 5-aminolevulinic acid hydrochloride, a substance used in photodynamic therapy (PDT), and can be used as a cosmetic composition for improving acne-prone skin.

[0050] In a composition containing 5-aminolevulinic acid hydrochloride according to another embodiment of the technical concept of the present invention, the cosmetic composition for improving acne-prone skin contains 5-aminolevulinic acid hydrochloride, fermented Baasob extract, Cordyceps sinensis extract, Kuril shrimp oil, sodium polydeoxyribonucleotide, propylene glycol, hyaluronidase, L-carnitine, caffeine, Origanum vulgare leaf oil, ascorbic acid (Vitamin C), allantoin, cetyl alcohol and mineral water.

[0051] In addition, the cosmetic composition for improving acne-prone skin containing 5-aminolevulinic acid hydrochloride according to the present invention contains 8 to 12% by weight of 5-aminolevulinic acid hydrochloride, 0.1 to 2.5% by weight of fermented Baasob extract, 1 to 3% by weight of Cordyceps sinensis extract, 0.5 to 1.5% by weight of Kuril shrimp oil, 1 to 2% by weight of sodium polydeoxyribonucleotide, 10 to 20% by weight of propylene glycol, 1 to 3% by weight of hyaluronidase, 3 to 5% by weight of L-carnitine, 2 to 4% by weight of caffeine, 0.1 to 1.0% by weight of Origanum Vulgare Leaf oil, 1 to 5% by weight of ascorbic acid (Vitamin C), 1 to 3% by weight of allantoin, 5 to 10% by weight of cetyl alcohol, and the balance of mineral water.

[0052] The fermented ginseng extract can be produced by extracting fermented ginseng. Codonopsis lanceolata is a perennial plant belonging to the family Codonopsisaceae, which grows wild in mountainous areas of Korea, China and Japan and whose roots are edible. It has long been known as one of the five ginseng plants along with Korean ginseng and has been widely used in food and herbal medicine.

[0053] The main components of ginseng include polyphenols, saponins, triterpenes, steroid compounds, and polyacetylenes such as lobetyolin. They have been reported to have physiological activities such as neutral lipid and cholesterol suppression, antioxidant properties, anti-mutation properties, and anti-tumor properties, and research is ongoing to use them as ingredients for health functional foods.

[0054] In addition, in traditional Chinese medicine, ginseng is known for its excellent effects of reducing swelling, strengthening the body, reducing fever, clearing gallbladder, draining pus, promoting recovery from illness, and promoting milk secretion, and has therefore been used for the purpose of treating illnesses.

[0055] The fermented B. difficile extract may be prepared by the following method.

[0056] First, ginseng root can be prepared and then washed to remove foreign matter.

[0057] In this step, the prepared ginseng is washed with purified water to remove foreign matter adhering to the ginseng.

[0058] Next, the washed ginseng can be dried to remove any moisture remaining inside the ginseng.

[0059] This step may be carried out using a dryer or shade to prevent the moisture contained in the washed ginseng from evaporating rapidly during drying in the sun and losing its inherent aroma. For example, the washed ginseng may be dried for 40 to 60 hours in a dryer maintained at a temperature of 23 to 27°C.

[0060] That is, in this step, the moisture contained in the ginseng is evaporated gradually and uniformly under the process conditions described above, and the fermentation process can be promoted by facilitating the penetration of air due to the destruction of the ginseng cell tissue.

[0061] Next, a fermentation culture solution for fermenting the dried ginseng can be prepared.

[0062] In the above step, the fermentation bacteria culture liquid may be prepared by the following method.

[0063] In order to prepare the fermentation bacteria culture liquid, first, non-sticky rice bran may be prepared, washed, and then soaked in water to soften the non-sticky rice bran.

[0064] This step can be carried out by soaking the washed non-sticky rice in water at a temperature of 25 to 30° C. for 50 to 100 minutes.

[0065] The soaked non-sticky rice can then be heated to produce hard rice.

[0066] In this step, the softened non-sticky rice is mixed with 1.5 to 2 times the weight of water, and then heated at a heat source of 110 to 130°C for 50 to 100 minutes to produce strong rice suitable for culturing fermentation bacteria.

[0067] Next, the fermentation bacteria culture liquid can be produced by mixing the hardened rice with fermentation bacteria, yeast, minerals and purified water.

[0068] In this step, the mixture may be 100 parts by weight of the total rice, and may be mixed in the following weight ratios: 3 to 7 parts by weight of fermentation bacteria, 4 to 8 parts by weight of yeast, 0.5 to 1.5 parts by weight of minerals, and 80 to 120 parts by weight of purified water.

[0069] As the fermentation fungus, yellow koji mold (Aspergillus oryzae) can be used, which is a known fungus used in the production of soy sauce, has excellent starch decomposition ability, and its optimum growth temperature is usually around 30° C. It prefers hot and humid conditions, and produces organic acids such as kojic acid and gluconic acid. In addition, the yellow koji mold is an excellent fermentation fungus that can be widely used to produce soy sauce, miso, gochujang, etc., by utilizing the action of amylase, i.e., the ability to decompose green powder into sugar, and the yellow koji mold can be a commercially available known yellow koji mold.

[0070] The mineral refers to a mineral substance that is absorbed by the ginseng during the fermentation and digestion process of the ginseng and is a nutritional substance necessary in relatively small amounts for the growth, maintenance and reproduction of the human body, and may be any one or more selected from the group consisting of calcium, phosphorus, potassium, magnesium, manganese, iodine, selenium, molybdenum and cobalt.

[0071] Then, the dried ginseng and a fermentation bacteria culture solution are mixed to ferment the ginseng, thereby producing fermented ginseng.

[0072] In this step, 100 parts by weight of the dried ginseng are mixed with 30 to 50 parts by weight of the fermentation bacteria culture solution, and then fermented at a temperature of 24 to 26° C. for 20 to 40 hours. If the fermentation is performed below the lower limit, the ginseng may not be fully fermented, and if the fermentation is performed above the upper limit, the physical properties of the fermented ginseng may be reduced.

[0073] Next, the fermented ginseng is washed and cut, and the cut fermented ginseng is dried to remove moisture remaining in the cut fermented ginseng.

[0074] In this step, the fermented ginseng can be cut into a certain length and then dried in a dryer maintained at a temperature of 30 to 35° C. for 30 to 40 hours.

[0075] Next, the cut and dried fermented ginseng is heated to separate the cores and then aged to produce fermented ginseng.

[0076] In this step, 100 parts by weight of the cut and dried fermented ginseng are mixed with 2000 to 3000 parts by weight of a mixture of paraffin and edible oil in a 1:1 ratio, and then the mixture is heated at a temperature of 90 to 95°C for 10 to 20 minutes, and then steamed at a temperature of 80 to 85°C for 40 to 50 minutes while maintaining the temperature, and aged at a temperature of 75 to 80°C for 5 to 10 minutes to perform one round of rinsing and aging process. By repeating the above process 10 times, a fermented ginseng can be produced.

[0077] In the above step, the paraffin may be liquid paraffin, which is a non-drying oil that does not dry out and is a hydrocarbon-based mineral oil, for example, NF or FDA Grade, with a molecular weight of C8 to C 32White mineral oils in the range can be used. In this case, the kinetic viscosity standard is ISO VG (Viscosity Grade) and can range from 6 to 100 CST at 37.8℃.

[0078] In addition, edible oils are fatty acid esters of glycerol (Glyceride) obtained from animal or plant seeds, nuts, fruits, etc., and are used as seasonings to add flavor when cooking food, or are widely used for deep-frying or stir-frying various fish or meats.

[0079] The fermented baasob can then be extracted to produce a fermented baasob extract.

[0080] In the above step, the extraction of the fermented fermented sorbent may be performed using a known extraction method, and for the sake of convenience and clarity of the technical idea of ​​the present invention, a detailed description of the extraction of the fermented fermented sorbent will be omitted.

[0081] The cordyceps extract can be produced by extracting the useful components of cordyceps. Cordyceps is known to have a physiologically active substance called cordycepin, which is a natural compound of 3'-deoxyadenosine and has been shown in clinical trials to have antibacterial, antitumor and anticancer effects.

[0082] In particular, Cordyceps sinensis contains a relatively large amount of cordycepin among many other cordyceps sinensis, and its fruiting body is known to protect the lungs and strengthen the kidneys. It is not only widely recognized for its effectiveness in treating tuberculosis and jaundice and as a tonic, but is also used as a high-priced herbal medicine mainly for post-illness physical regulation and as a tonic.

[0083] In addition, the medicinal components of Cordyceps sinensis include properties that strengthen immune function, and are effective against colds, pulmonary tuberculosis, late cough, asthma, seizures, anemia, male sexual dysfunction, and high blood pressure. In addition to cordycepin, it also contains a large amount of polysaccharides, including D-mannitol and quinic acid, and is known to have a high content of various amino acids.

[0084] The Cordyceps sinensis extract may be prepared by the following method.

[0085] First, the cordyceps can be washed to remove foreign matter adhering to the surface of the cordyceps.

[0086] In this step, the cordyceps may be immersed in a mixed solution of lemon juice and salt solution for 3 to 5 minutes, and then the cordyceps may be washed with purified water, and the lemon juice and salt solution may be mixed in a weight ratio of 1:4.

[0087] The lemon juice and the salt solution can sterilize the cordyceps and prevent it from spoiling easily, and the salt solution can have a concentration of 1 to 3% by weight.

[0088] Next, the washed cordyceps can be irradiated with microwaves in a reduced pressure atmosphere and vacuum dried.

[0089] This step may be performed by irradiating the washed cordyceps with microwaves under a pressure of 60 to 70 mbar, and this step may be performed at a temperature of 40 to 50°C for 5 to 10 minutes, and may proceed by irradiating the washed cordyceps with microwaves of 2.2 GHz.

[0090] The microwaves can penetrate into the inside of the cordyceps and heat it, and when the microwaves are irradiated, the water molecules inside the cordyceps vibrate or rotate due to the polarity change of the microwaves, and this polarized vibration can lead to friction between molecules and cause a heat generation phenomenon. When the cordyceps is dried by irradiating microwaves under reduced pressure, the cordyceps swells due to heating inside, and this instantaneous internal heating and swelling destroys the cell membrane inside the cordyceps, resulting in a sterilizing effect. In addition, the swelling due to heating inside the cordyceps allows the effective ingredients of the cordyceps to be effectively extracted during subsequent extraction.

[0091] Next, the vacuum-dried Cordyceps sinensis can be aged, and in this step, the vacuum-dried Cordyceps sinensis can be stored at a temperature of 10 to 15°C for 30 to 40 hours to stabilize the physical properties of the Cordyceps sinensis.

[0092] Next, the aged Cordyceps sinensis is mixed with purified water and then heated to produce a Cordyceps sinensis extract in which useful components of Cordyceps sinensis have been exuded.

[0093] In the above step, the cordyceps sinensis can be mixed in a weight ratio of 1000 to 1500 g per 10 to 12 liters (L) of purified water, and then heated for 60 to 80 minutes at a temperature of 90 to 95°C, and then heated for 300 to 400 minutes at a temperature of 70 to 75°C.

[0094] If this step is performed below the lower limit of the range, there may be a problem that the useful ingredients of Cordyceps sinensis are not sufficiently extracted, and if it is performed above the upper limit of the range, there may be a problem that Cordyceps sinensis residue is generated and the physical properties of the Cordyceps sinensis extract are reduced.

[0095] The kuril shrimp oil can be produced using kuril shrimp, which is known to contain phospholipid compounds with a structure similar to that of components of human cell membranes, and therefore, the oil extracted from kuril shrimp is known to be better absorbed by the human body than other fish oils.

[0096] In addition to lipids such as omega-3, krill oil also contains vitamins A, E, and D, and in particular, a substance called astaxanthin, which is a powerful antioxidant. It has been reported that krill oil's antioxidant function is 48 times that of regular fish oil.

[0097] That is, nutritionally, kuril shrimp is composed of high-quality protein and lipids, and fresh kuril shrimp contains up to 10% lipids, and the lipids of kuril shrimp contain approximately 40% highly unsaturated fatty acids omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and approximately 40-50% phospholipids. In addition, it contains astaxanthin, a fat-soluble carotenoid antioxidant, which is useful.

[0098] In order to produce the kuril shrimp oil, first, kuril shrimp are prepared and washed, and then the washed kuril shrimp can be dried.

[0099] The drying of the washed kuril shrimp may include a first drying and a second drying, and the first drying may be performed by drying the washed kuril shrimp at a temperature of 50 to 60° C. for 5 to 15 hours to primarily remove moisture remaining in the washed kuril shrimp.

[0100] Also, the second drying may be performed by drying the first dried kuril shrimp with hot air, and the second drying may be performed by subjecting the first dried kuril shrimp to hot air at a temperature of 110 to 130° C. for 30 to 50 minutes.

[0101] Next, the second dried kuril shrimp can be crushed into powder and then aged to produce aged kuril shrimp powder.

[0102] In the above step, the crushing of the second dried shrimp may be performed by crushing the second dried shrimp into powder having a particle size of 5 to 10 mm, and the maturation of the powdered shrimp may be performed by storing the powdered shrimp at a temperature of 6 to 8° C. for 20 to 40 hours.

[0103] Next, the aged kurile shrimp powder can be mixed with an enzyme and an acid, and then stored for enzymatic decomposition.

[0104] That is, in the above step, the aged powder of kuril shrimp is mixed with an enzyme and an acid, and then the aged powder of kuril shrimp mixed with the enzyme and the acid is stored at a temperature of 36 to 38° C. for 10 to 30 hours to be enzymatically decomposed. The enzymatic decomposition of the aged powder of kuril shrimp can be performed using an enzyme capable of separating proteins, chitin, and immunoactive polysaccharides present in the kuril shrimp.

[0105] In the above step, commercially available known protease, chitinase, pectinase, and xylanase can be used as the enzyme, and citric acid and ascorbic acid can be used as the acid. Specifically, the following weight ratios are mixed with respect to 100 parts by weight of the aged kuril shrimp powder: 0.01 to 0.03 parts by weight of protease, 0.03 to 0.05 parts by weight of chitinase, 0.005 to 0.009 parts by weight of pectinase, 0.008 to 0.012 parts by weight of xylanase, 0.01 to 0.1 parts by weight of citric acid, and 0.01 to 0.1 parts by weight of ascorbic acid, so that the pH of the aged kuril shrimp powder mixed with the enzymes and acids can be adjusted to 3.5 to 6.5.

[0106] Next, the oil is separated from the enzymatically decomposed aged kuril shrimp powder to produce kuril shrimp oil.

[0107] The method for extracting oil from the enzymatically hydrolyzed aged kuril shrimp powder in the above step is well known to those skilled in the art, and therefore, for the sake of convenience and clarity of the technical idea of ​​the present invention, detailed description thereof will be omitted.

[0108] The polydeoxyribonucleotide sodium can alleviate inflammation of damaged tissues and promote cell regeneration. For example, the polydeoxyribonucleotide sodium can interact with adenosine receptors to promote the expression of vascular endothelial growth factor, thereby promoting wound healing, and can promote the growth of epithelial cells, promote the maturation of extracellular matrix, and increase the density of microvessels, thereby promoting angiogenesis.

[0109] The propylene glycol prevents the cosmetic composition from changing or decomposing, thereby maintaining the safety of the cosmetic composition, has an antibacterial effect and inhibits the growth of bacteria, and can act as a humectant, moisturizer, and preservative.

[0110] Aminophylline functions as a PDE (phosphodiesterase) inhibitor and can be used to promote lipid breakdown.

[0111] Hyaluronidase is excreted through lymph after destroying fat cells, and when used together with aminophylline, it can regulate the release of aminophylline, helping to reduce swelling and improve circulation.

[0112] L-carnitine binds to fatty acids to transport and utilize them as energy, and fatty acids inhibit feedback, secrete ATP, increase lipolytic enzyme activity, and cause the hydrolysis of neutral fats.

[0113] Caffeine functions as a PDE (phosphodiesterase) inhibitor and can promote lipolysis.

[0114] The origanum vulgare leaf oil can be produced using oregano leaves. Oregano (Oregano or Origanum vulgare) is native to the Mediterranean coast and was used for medicinal purposes in ancient Greece and in cooking in ancient Rome. It is not only harmless to the human body but also beneficial, as it is still used today as a natural preservative for meat storage and a spice in Italian cuisine.

[0115] Oregano, also known as a natural antibiotic, is rich in phenolic acids and flavonoids and has high antioxidant activity. It is also said to have tonic, diuretic, stomachic, appetite-boosting, sedative and antiseptic effects, as well as to treat headaches, nausea and insomnia. It is a herb that is mainly used as tea or as a bath additive, and is beneficial to the human body.

[0116] Ascorbic acid (Vitamin C) is involved in the synthesis of collagen, the main protein that constitutes connective tissues such as skin, bones, blood vessels, and cartilage, and is used as a coenzyme in various enzyme reactions in the body. In addition, ascorbic acid (Vitamin C) converts iron into a reduced form in the small intestine, increasing the absorption of plant-based iron that is not bound to hemoglobin, and also has the effect of preventing inflammation and aging.

[0117] The allantoin helps to soothe the skin and activate cells, the cetyl alcohol is used as a water-soluble thickener, and the mineral water can function as a solvent to disperse and dissolve the composition.

[0118] Hereinafter, a cosmetic composition for improving acne-prone skin, comprising 5-aminolevulinic acid hydrochloride according to another embodiment of the technical concept of the present invention, will be described in more detail with reference to the accompanying drawings.

[0119] <Example> A cosmetic composition for improving acne-prone skin was prepared by mixing 10% by weight of 5-aminolevulinic acid hydrochloride, 1.5% by weight of fermented Baasob extract, 2% by weight of cordyceps sinensis extract, 1% by weight of kuril shrimp oil, 1.5% by weight of sodium polydeoxyribonucleotide, 15% by weight of propylene glycol, 2% by weight of hyaluronidase, 4% by weight of L-carnitine, 3% by weight of caffeine, 0.5% by weight of Origanum Vulgare Leaf oil, 3% by weight of ascorbic acid (Vitamin C), 2% by weight of allantoin, 8% by weight of cetyl alcohol, and the remaining amount of mineral water.

[0120] <Comparative Example> A commercially available acne ointment (manufactured by Company P) was prepared and then used in the cosmetic composition for improving acne-prone skin according to the comparative example.

[0121] 1. Antibacterial activity evaluation experiment The following experiment was carried out to evaluate the antibacterial activity of the cosmetic compositions for improving acne-prone skin according to the Examples and Comparative Examples. In the antibacterial activity evaluation experiment, Propionibacterium acnes ATCC 6919, which is a type of acne bacterium, was used as the test bacterium.

[0122] After each P. acnes was inoculated into BHI broth and pre-cultured, each composition was inoculated at a concentration of 1% into 100 ml of fresh sterilized BHI broth containing 5% each composition, and the bacteria were then cultured in an anaerobic incubator for 2 days, after which the number of bacteria was measured.

[0123] [Table 1]

[0124] Referring to Table 1, it can be seen that the cosmetic composition for improving acne skin prepared according to the examples has significantly improved antibacterial activity against Propionibacterium acnes.

[0125] 2. Antioxidant activity experiment The cosmetic composition for improving acne-prone skin according to the embodiment was used as a sample to measure radical scavenging activity.

[0126] The antioxidant activity (electron donation ability, EDA%) of the sample was measured by a modified Blois method. 2 mL of the sample was mixed with 2 mL of 0.2 mM DPPH (1,1-diphenyl-2-picryl hydrazyl) solution, and the mixture was left for 30 minutes before measuring the absorbance at 517 nm.

[0127] Radical scavenging activity is shown as the rate of absorbance decrease between the sample-added area and the non-added area. Radical scavenging activity was calculated using the following formula, and the results are shown in Table 2 below. BHT (a synthetic antioxidant) was used as a control sample.

[0128] Radical scavenging activity (%) = (1 - absorbance of sample added / absorbance of non-added sample) x 100

[0129] [Table 2]

[0130] Referring to Table 2, it was found that the cosmetic composition for improving acne-prone skin prepared according to the examples has excellent antioxidant activity, and is more effective in scavenging radicals than the conventional synthetic antioxidant used in the control group.

[0131] Therefore, the cosmetic composition for improving acne-prone skin prepared according to the examples is expected to have excellent antioxidant effects for improving acne-prone skin against active oxygen and free radicals, and to significantly enhance the physiological activity of acne-prone skin.

[0132] 3. Sebum secretion suppression efficacy evaluation The cosmetic compositions for improving acne-prone skin prepared in the Examples and Comparative Examples were analyzed for their sebum excretion suppressing effect.

[0133] The sebum secretion suppression effect was analyzed by dividing 30 women and men aged 15 to 25 with oily skin into 3 groups of 10 people each, and having them apply the cosmetic compositions for improving acne-prone skin of the Examples and Comparative Examples to their faces twice a day, in the morning and evening, and then measuring the amount of sebum secretion on their faces using a skin oil and moisture meter after 5 days.

[0134] The experiment was carried out under constant temperature and humidity conditions of 23°C and 42% relative humidity, and the amount of sebum secretion was set as the base value. After applying the cosmetic compositions for improving acne-prone skin according to the examples and comparative examples, the change in the amount of sebum secretion was measured to evaluate the sebum suppression effect, and the change in the amount of sebum secretion compared to the initial value was calculated using the following [Equation 1], and the results (average value for each group) are shown in [Table 3] and Figure 1. (Here, St=0 indicates the initial amount of sebum secretion before application, and St=i indicates the amount of sebum secretion 5 days after application.)

[0135] The control group was used to analyze the effect of inhibiting sebum excretion in subjects who had not applied the cosmetic composition for improving acne-prone skin.

[0136] [Formula 1] Sebum secretion amount = (S t=0 -S t=i )S t=0 ×100

[0137] [Table 3]

[0138] FIG. 2 is a graph showing the change in sebum secretion after applying cosmetic compositions for improving acne-prone skin according to Examples and Comparative Examples to the acne-prone skin of subjects for five days.

[0139] Referring to Table 3 and FIG. 2, it was confirmed that the cosmetic composition for improving acne-prone skin according to the Example had a superior sebum secretion suppressing effect compared to the cosmetic composition for improving acne-prone skin according to the Comparative Example.

[0140] 4.Measurement of inflammation relief effect The inflammation-reducing effect of each of the cosmetic compositions for improving acne-prone skin according to the Examples and Comparative Examples was measured. First, macrophages (Raw 2647 mouse cells) were placed in a 96-well microplate at 4 × 10 cells per well. 5 After dividing the cells into individual cells, the cells were treated with the compositions of the Examples and Comparative Examples at a concentration of 1,000 μg / ml for 20 hours at 35° C. and 5% CO2. After the treatment, the supernatant was collected and the amount of TNF-α was measured using a sandwich ELISA method, and the results are shown in Table 4 below.

[0141] [Table 4]

[0142] Referring to Table 4, it can be seen that the cosmetic composition for improving acne-prone skin according to the embodiment shows a higher TNF-α inducing effect than the comparative example, and that the cosmetic composition for improving acne-prone skin according to the embodiment has an excellent immune enhancing effect by increasing the activity of macrophages through induction of TNF-α production.

[0143] 5. Observation of acne improvement The cosmetic composition prepared according to the embodiment was applied to the acne-prone skin of the subject, and then a photodynamic therapy (PDT) experiment was performed. After a certain period of time, the condition of the acne-prone skin of the subject was observed.

[0144] Figures 3a, 4a, 5a, and 6a are photographs showing the condition of acne-prone skin of a subject before using the cosmetic composition prepared according to the embodiment, and Figures 3b, 4b, 5b, and 6b are photographs showing the condition of acne-prone skin of a subject after using the cosmetic composition prepared according to the embodiment once a day for 20 days.

[0145] 3a to 6b, it can be seen that the acne-prone skin condition (FIGS. 3b, 4b, 5b, and 6b) of the subject after using the cosmetic composition prepared according to the embodiment was improved compared to the acne-prone skin condition (FIGS. 3a, 4a, 5a, and 6a) before using the cosmetic composition prepared according to the embodiment.

[0146] Hereinafter, an embodiment of photoepidemiological treatment using a composition containing 5-aminolevulinic acid hydrochloride according to the present invention will be described in detail with reference to Figs. 7a and 7b.

[0147] Meanwhile, in the following examples, oral administration of the photoepidemiological therapeutic composition according to the present invention will be described as an example, however, the method of taking the photoepidemiological therapeutic composition according to the technical idea of ​​the present invention is not limited to oral administration.

[0148] That is, the photoepidemiological therapeutic composition containing 5-aminolevulinic acid hydrochloride according to the present invention can be prepared in various forms and administered to a patient. For example, the photoepidemiological therapeutic composition containing 5-aminolevulinic acid hydrochloride according to the present invention can be prepared in the form of an oral or topical medication and used.

[0149] Specifically, the oral medications can be prepared and administered in various known forms such as tablets, powders, granules, liquids, syrups, and drinks, and the external medications can be prepared and administered in various known forms such as patches, ointments / creams / gels / liquids, and injections.

[0150] The photoepidemiological treatment composition containing 5-aminolevulinic acid hydrochloride according to the present invention comprises 5-aminolevulinic acid hydrochloride, indole-3-acetic acid (IAA), polyethyleneimine, self-assembled ligand particles, purified water, a carrier, a glycerol fatty acid ester, and an emulsifier.

[0151] In addition, the photoepidemiological treatment composition containing 5-aminolevulinic acid hydrochloride according to the present invention may contain 30 to 50 parts by weight of 5-aminolevulinic acid hydrochloride, 10 to 20 parts by weight of indole-3-acetic acid (IAA), 1 to 5 parts by weight of polyethyleneimine, 5 to 15 parts by weight of self-assembled ligand particles, 10 to 20 parts by weight of purified water, 10 to 20 parts by weight of a carrier, 20 to 30 parts by weight of a glycerin fatty acid ester, and 10 to 20 parts by weight of an emulsifier.

[0152] In addition, the photoepidemiological therapy composition containing 5-aminolevulinic acid hydrochloride according to the present invention contains 5-aminolevulinic acid hydrochloride, indole-3-acetic acid (IAA), polyethyleneimine, self-assembled ligand particles, a carrier, a glycerol fatty acid ester, and an emulsifier. The photoepidemiological therapy composition is orally administered to a patient in an amount appropriate for the patient's body weight. After six hours, the tumor site of the patient is photoactivated in vivo by irradiating the tumor site with light in the wavelength range of 660 to 680 nm, causing the tumor site to emit fluorescent or phosphorescent colors.

[0153] Specifically, when the photoepidemiological therapeutic composition containing 5-aminolevulinic acid hydrochloride according to the present invention is prepared in the form of a liquid medicine, if the patient weighs 60 kg or less, one vial of the liquid medicine prepared in 10 cc can be administered and the glioblastoma surgery can be performed 6 hours later, and if the patient weighs more than 60 kg, one vial of the liquid medicine prepared in 10 cc can be administered twice, i.e., two vials of the liquid medicine can be administered and the glioblastoma surgery can be performed 6 hours later.

[0154] After the patient takes 5-aminolevulinic acid hydrochloride, the tumor site will emit a fluorescent color, allowing the tumor site to be removed while protecting normal cell tissue from damage during surgery.

[0155] That is, 5-aminolevulinic acid hydrochloride is a substance that can be used in photodynamic therapy (PDT), which is a technology that uses photosensitizers (hereinafter referred to as photosensitizers) to treat intractable diseases such as cancer without surgery.

[0156] Research into photodiode therapy (PDT) has been actively conducted since the beginning of the 20th century, and is currently used in the diagnosis and treatment of cancer, allogeneic and autologous bone marrow transplants, resolution of graft-versus-host reaction through extracorporeal photopheresis, treatment of infectious diseases such as antibiotics and AIDS, organ and skin graft surgery, and treatment of arthritis and spinal muscular atrophy.

[0157] In addition, photodynamic therapy (PDT) is being used to strengthen the immune system and control and regulate immune responses, and its range of applications is gradually expanding to include regenerative medicine, biosensors, and optogenetics.

[0158] In particular, photosensitizers, which are substances that react sensitively to light, are administered into the body. When light is irradiated from outside, singlet oxygen or free radicals are generated by a chemical reaction between the abundant oxygen in the body and the external light, and this singlet oxygen or free radicals induces and destroys various lesions and cancer cells. This is a treatment method that utilizes the principle.

[0159] Currently, photosensitizers used in photodialysis therapy (PDT) include porphyrin derivatives, chlorin, bacteriochlorin, phthalocyanine, 5-aminolevulinic acid derivatives, porfimer sodium, etc., and 5-aminolevulinic acid hydrochloride can be used in the photodialysis therapy composition of the present invention.

[0160] 5-aminolevulinic acid hydrochloride is a C-5 aliphatic compound represented by the following formula 2, and is involved in the biosynthesis of tetrapyrroles (prophyrin, chlorophyll, heme, vitamin B) in various organisms. 12 It is one of the intermediate substances discovered in the process of synthesis, synthesis, etc.

[0161] [ka]

[0162] The indole-3-acetic acid (IAA) functions as a photosensitizer and has the property of being activated by light. When the indole-3-acetic acid (IAA) is used together with the 5-aminolevulinic acid hydrochloride, it can be photoactivated by ultraviolet or visible light to make the tumor site of the patient fluoresce or phosphoresce.

[0163] The indole-3-acetic acid (IAA) can be represented by the following formula 3.

[0164] [ka]

[0165] The polyethyleneimine can be used as a biocompatible polymer, and the polyethyleneimine shows excellent stability in the body when orally administered, has a high biodistribution in the blood, and can be continuously accumulated at the tumor site for a sufficient period of time, causing the tumor site of the patient to emit a fluorescent or phosphorescent color.

[0166] Polyethylenimine is widely used as a gene carrier, and since it has many amine groups, it has the property of being highly soluble in water-soluble solvents. In the present invention, the polyethyleneimine may be commercially available in a known composition.

[0167] The self-assembled ligand particle is a ligand particle that specifically reacts with tumor cells and can be represented by the following [Chemical Formula 4].

[0168] [ka]

[0169] In the above [Chemical Formula 4], R 1 are independently hydrogen, halogen or linear or branched C 1‐10 alkyl, l is an integer from 2 or 3, m is an integer from 4 to 7, and n is an integer from 1000 to 10,000; TIFF0007629525000009.tif3043 is a ligand that specifically reacts with tumor cells, and is any one of biotin and folic acid.

[0170] The self-assembled ligand particle means a ligand that can bind to tumor cells, and the self-assembled ligand particle can serve to enable the photoepidemiological treatment composition according to the present invention to selectively and specifically bind to and act on the tumor site of a patient.

[0171] The carrier may be a substance in which lipids and α-lipoic acid are chemically bonded, and the photosensitizer generates reactive oxygen species when irradiated with light, and the α-lipoic acid scavenges the generated reactive oxygen species while releasing the composition from the tumor site of the patient, thereby enabling the components of the photoepidemiological treatment composition to be stably delivered to the tumor site of the patient.

[0172] The lipid constituting the carrier may be any one or more selected from the group consisting of L-α-phosphatidylcholine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine.

[0173] The aforementioned α-lipoic acid (LA) is an essential element of mitochondria and exists in various forms in both animals and plants, mainly acting as a coenzyme in enzyme reactions within mitochondria. It is known that it is biosynthesized in all cells, with octanoic acid being the precursor of the C-8 fatty acid chain of lipoic acid and cysteine ​​being the source of sulfur, resulting in the biosynthesis of lipoic acid.

[0174] Lipoic acid and its reduced form, dihydrolipoic acid, are well known as antioxidants that protect and enhance the effects of vitamins C, E and glutathione, inhibit NF-kB and act as an anti-inflammatory agent to inhibit tissue damage caused by ultraviolet rays. Lipoic acid has long been used as an important drug for various diseases in the field of pharmacology.

[0175] The glycerin fatty acid ester may be at least one selected from the group consisting of triacetin, tributyrin, tricaproin, tricaprylin, tricaprin, and triolein.

[0176] The emulsifier may be at least one selected from the group consisting of sorbitan ester (Span), polyoxyethylene sorbitan (Tween), and polyoxyethylene ether (Brij).

[0177] The photoepidemiological therapeutic composition containing 5-aminolevulinic acid hydrochloride according to the present invention will be described in more detail below with reference to the accompanying drawings.

[0178] <Example> A photoepidemiological treatment composition was prepared by mixing 40 parts by weight of 5-aminolevulinic acid hydrochloride, 15 parts by weight of indole-3-acetic acid (IAA), 3 parts by weight of polyethyleneimine, 10 parts by weight of self-assembled ligand particle, 15 parts by weight of purified water, 15 parts by weight of carrier chemically bound to lipid and α-lipoic acid, 25 parts by weight of glycerin fatty acid ester (triacetin), and 15 parts by weight of emulsifier (sorbitan ester (Span)).

[0179] The photoepidemiological treatment composition according to the above embodiment was orally administered to the patient at a dose of 35 mg / kg per body weight (kg), and after 6 hours, the tumor site of the patient was irradiated with light in the 670 nm wavelength range for in vivo photoactivation.

[0180] FIG. 7a is a photograph showing the location of a patient's brain tumor before the patient ingested a composition containing 5-aminolevulinic acid hydrochloride according to the present invention, and FIG. 7b is a photograph showing the state of the patient's brain tumor site emitting fluorescent light when a doctor performed surgery 6 hours after the patient ingested a composition containing 5-aminolevulinic acid hydrochloride according to the present invention.

[0181] Referring to Figures 7a and 7b, after a patient drinks a composition containing 5-aminolevulinic acid hydrochloride according to the present invention, when a doctor performs surgery 6 hours later, the tumor site in the patient's brain emits a fluorescent color, which indicates that only the tumor site can be safely removed without damaging or destroying normal tissues.

[0182] Although a preferred embodiment of the present invention has been described above, those skilled in the art will understand that the present invention can be embodied in other specific forms without changing the technical concept or essential features of the present invention. Therefore, the embodiment described above should be understood as illustrative in all respects and not restrictive.

[0183] (Mode for carrying out the invention) The embodiments for carrying out the invention have been described together in the above best mode for carrying out the invention. [Industrial Applicability]

[0184] The present invention can be used in various industrial fields related to compositions containing 5-aminolevulinic acid hydrochloride.

Claims

1. A composition comprising 5-aminolevulinic acid hydrochloride, which is a substance used in photoimmunotherapy, fermented baasob extract, cordyceps sinensis extract, kuril shrimp oil, sodium polydeoxyribonucleotide, propylene glycol, hyaluronidase, L-carnitine, caffeine, origanum vulgare leaf oil, ascorbic acid, allantoin, cetyl alcohol and mineral water, and used as a cosmetic composition for improving acne-prone skin.

2. The 5-aminolevulinic acid hydrochloride is 8 to 12% by weight, fermented Baasob extract is 0.1 to 2.5% by weight, cordyceps extract is 1 to 3% by weight, kuril shrimp oil is 0.5 to 1.5% by weight, polydeoxyribonucleotide sodium is 1 to 2% by weight, propylene glycol is 10 to 20% by weight, hyaluronidase is 1 to 3% by weight, L-carnitine is 3 to 5% by weight, caffeine is 2 to 4% by weight, origanum vulgare leaf oil is 0.1 to 1.0% by weight, ascorbic acid (Vitamin C) is 1 to 5% by weight, allantoin is 1 to 3% by weight, cetanol is 1 to 5% by weight, and cetanol is 1 to 5% by weight.

2. The composition according to claim 1, comprising 5 to 10% by weight of 5-aminolevulinic acid hydrochloride and the balance being mineral water.

3. A composition comprising 5-aminolevulinic acid hydrochloride, which is a substance used in photoimmunotherapy, indole-3-acetic acid (IAA), polyethyleneimine, self-assembled ligand particles, purified water, a carrier, a glycerol fatty acid ester, and an emulsifier, characterized in that the composition is used as an oral pharmaceutical composition for fluorescence-induced visualization of malignant tissue.

4. The composition according to claim 3, comprising 30 to 50 parts by weight of 5-aminolevulinic acid hydrochloride, 10 to 20 parts by weight of indole-3-acetic acid (IAA), 1 to 5 parts by weight of polyethyleneimine, 5 to 15 parts by weight of self-assembled ligand particles, 10 to 20 parts by weight of purified water, 10 to 20 parts by weight of a carrier, 20 to 30 parts by weight of a glycerin fatty acid ester, and 10 to 20 parts by weight of an emulsifier.

5. The composition according to claim 4, characterized in that the photoepidemiological treatment composition comprising 5-aminolevulinic acid hydrochloride, indole-3-acetic acid (IAA), polyethyleneimine, self-assembled ligand particles, a carrier, a glycerol fatty acid ester and an emulsifier is administered to a patient at a dose of 35 mg / kg per body weight (kg), and then, 6 hours later, light having a wavelength of 660 to 680 nm is irradiated to the tumor site of the patient to photoactivate the tumor in vivo.

Citation Information

Patent Citations

  • Preparation method of antibacterial mask cream

    CN109771612A

  • Pyridinone compounds for use in photodynamic therapy

    JP2015526499A

  • Preparation method of 5-aminolevulinic acid and Use of the same

    KR1020140135506A

  • Composition for the treatment or improvement of Acne dermatitis comprising 5-aminolevulinic acid hydrochloride and its derivatives

    KR1020200058699A

  • KR10‐1135147