KR102006784B1 - Composition for treating wound comprising non thermal plasma treated solution - Google Patents
Composition for treating wound comprising non thermal plasma treated solution Download PDFInfo
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- KR102006784B1 KR102006784B1 KR1020170110761A KR20170110761A KR102006784B1 KR 102006784 B1 KR102006784 B1 KR 102006784B1 KR 1020170110761 A KR1020170110761 A KR 1020170110761A KR 20170110761 A KR20170110761 A KR 20170110761A KR 102006784 B1 KR102006784 B1 KR 102006784B1
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- plasma
- composition
- present
- wound
- growth factor
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
본 발명은 액상 플라즈마를 포함하는 상처 치료용 조성물에 관한 것이다. 보다 구체적으로, 본 발명은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 약제학적 조성물, 의약외품 조성물, 건강기능식품 조성물, 및 상기 조성물을 개체에 투여하는 단계 또는 개체의 피부에 도포하는 단계를 포함하는 상처 치료 방법에 관한 것이다. 본 발명의 액상 플라즈마 및 성장인자를 포함하는 조성물은 섬유아세포의 증식을 유도함으로써 상처 치료 효능이 뛰어나, 상처 치료를 위한 피부 외용제를 비롯한 의약품 등에 적용되어 유용하게 사용될 수 있을 것이다.The present invention relates to a wound healing composition comprising a liquid plasma. More specifically, the present invention provides a pharmaceutical composition for treating wounds, a quasi-drug composition, a nutraceutical composition, and administering the composition to the subject or applying it to the skin of the subject, including liquid plasma and growth factors as active ingredients. It relates to a wound treatment method comprising a. The composition comprising the liquid plasma and the growth factor of the present invention is excellent in wound healing effect by inducing proliferation of fibroblasts, and may be usefully applied to medicines including skin external preparations for wound treatment.
Description
본 발명은 액상 플라즈마를 포함하는 상처 치료용 조성물에 관한 것이다. 보다 구체적으로, 본 발명은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 약제학적 조성물, 의약외품 조성물, 건강기능식품 조성물, 및 상기 조성물을 개체에 투여하는 단계 또는 개체의 피부에 도포하는 단계를 포함하는 상처 치료 방법에 관한 것이다. 본 발명의 액상 플라즈마 및 성장인자를 포함하는 조성물은 섬유아세포의 증식을 유도함으로써 상처 치료 효능이 뛰어나, 상처 치료를 위한 피부 외용제를 비롯한 의약품 등에 적용되어 유용하게 사용될 수 있을 것이다.The present invention relates to a wound healing composition comprising a liquid plasma. More specifically, the present invention provides a pharmaceutical composition for treating wounds, a quasi-drug composition, a nutraceutical composition, and administering the composition to the subject or applying it to the skin of the subject, including liquid plasma and growth factors as active ingredients. It relates to a wound treatment method comprising a. The composition comprising the liquid plasma and the growth factor of the present invention is excellent in wound healing effect by inducing proliferation of fibroblasts, and may be usefully applied to medicines including skin external preparations for wound treatment.
피부는 신체를 보호하는 방어막 역할을 수행하고 질환에 대한 신체의 일차 방어선이며, 표피(epidermis)가 미생물 침입에 대한 장벽을 제공한다. 따라서 상처, 화상, 찰과상 및 피부에 대한 기타 손상의 치료에서 일차적인 목적은 감염을 예방하기 위한 신속한 봉합(closure) 및 상처 치유이다. 상처 치유는 일반적으로, 염증(inflammation), 증식(proliferation) 및 재형성(remodelling)의 3가지 단계를 수반하는 복잡한 과정이다. 첫 번째 단계는 지혈(haemostasis)을 달성하기 위한 응고(clotting), 그리고 세균 및 괴사 조직을 파괴하기 위한 호중구의 보충, 그 이후에 대식세포의 보충을 수반한다. 두 번째 단계 동안, 혈관신생(angiogenesis)이 발생하고, 이때 내피 세포가 상처 부위로 들어가고, 이와 동시에 섬유아세포가 상처 부위로 들어가고 육아 조직(granulation tissue)을 생산하는데 도움을 준다. 육아 조직의 형성은 재상피화(reepithelialisation)가 일어날 수 있도록 한다. 최종 단계 동안, 콜라겐 생산과 파괴의 수준이 균등해지고, 그리고 치유된 상처는 최대 강도를 달성하기 위하여 천천히 변경된다. 상처 치유는 이들 과정 중에서 임의의 한 가지가 적절하게 또는 시기 적절한 방식으로 기능하지 않을 때, 지연되거나 손상된다. 이것은 만성적인 상처를 유발할 수 있는데, 이러한 상처는 개인에게 중요한 문제일 뿐만 아니라 비용이 많이 드는 임상적 문제점일 수 있다. The skin acts as a protective barrier to the body and is the body's primary line of defense against disease, and the epidermis provides a barrier to microbial invasion. Thus the primary objectives in the treatment of wounds, burns, abrasions and other damage to the skin are rapid closure and wound healing to prevent infection. Wound healing is a complex process that generally involves three stages: inflammation, proliferation, and remodeling. The first step involves clotting to achieve haemostasis, and supplementation of neutrophils to destroy bacteria and necrotic tissue, followed by supplementation of macrophages. During the second stage, angiogenesis occurs, where endothelial cells enter the wound site, while fibroblasts enter the wound site and help to produce granulation tissue. The formation of granulation tissue allows for re-epithelialization. During the final stage, the level of collagen production and destruction is evened, and the wound healed is slowly changed to achieve maximum strength. Wound healing is delayed or damaged when any one of these processes does not function properly or in a timely manner. This can lead to chronic wounds, which can be an important problem for an individual as well as an expensive clinical problem.
상기 상처 치유(wound closure)는 임상적으로 피부가 완전하게 봉합되는 것을 의미하며, 각질세포(keratinocyte), 섬유모세포(fibroblast), 혈관내피세포(endothelial cell), 대식세포(macrophage), 혈소판(platelet) 등 여러 종류의 세포가 상호작용하며 조절하는 복잡한 과정이다. 각각의 과정은 많은 성장인자(growth factor), 사이토카인(cytokine) 및 케모카인(chemokine)이 조절하는 복잡한 신호전달망에 의해 조절된다.Wound closure refers to the complete closure of the skin clinically, keratinocyte (fibroblast), fibroblast (endothelial cell), macrophage (macrophage), platelet (platelet) It is a complex process in which different kinds of cells interact and regulate. Each process is regulated by a complex signaling network regulated by many growth factors, cytokines and chemokines.
상처는 빠르게 치료해야 2차 감염의 위험을 줄일 수 있다. 또한, 상처치료 과정에서 염증반응이 지속되면 염증기에서 증식기로의 진행이 이루어지지 않아 정상적인 상처치유가 지연된다. 이러한 이유로 염증반응을 유도하지 않는 상처 치료방법의 개발이 활발하게 진행되고 있다.Wounds need to be treated quickly to reduce the risk of secondary infection. In addition, if the inflammatory response persists during wound healing, normal wound healing is delayed because the progression from the inflammatory phase to the proliferative phase is not made. For this reason, the development of wound treatment methods that do not induce an inflammatory response is actively progressing.
선행기술Prior Art
1. 국제공개특허 WO20161675161. International Publication WO2016167516
본 발명은 상기와 같은 종래 기술상의 문제점을 해결하기 위해 안출된 것으로, 액상 플라즈마를 포함하는 상처 치료용 조성물에 관한 것이다.The present invention has been made to solve the above problems in the prior art, and relates to a composition for treating wounds comprising a liquid plasma.
이에 본 발명자들은 상처의 근본적인 치료를 위한 방법을 개발하기 위하여 예의 노력한 결과, 섬유아세포(fibroblast)에 액상 플라즈마 및 상피세포 성장인자(epidermal growth factor. EGF)를 처리하는 경우 섬유아세포의 재생이 촉진됨을 확인하고 본 발명을 완성하기에 이르렀다. Therefore, the present inventors have made diligent efforts to develop a method for the fundamental treatment of wounds. When fibroblasts are treated with liquid plasma and epidermal growth factor (EGF), the regeneration of fibroblasts is promoted. It confirmed and completed this invention.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업계에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.
이하, 본원에 기재된 다양한 구체예가 도면을 참조로 기재된다. 하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세사항, 예컨대, 특이적 형태, 조성물, 및 공정 등이 기재되어 있다. 그러나, 특정의 구체예는 이들 특이적 상세 사항 중 하나 이상 없이, 또는 다른 공지된 방법 및 형태와 함께 실행될 수 있다. 다른 예에서, 공지된 공정 및 제조 기술은 본 발명을 불필요하게 모호하게 하지 않게 하기 위해서, 특정의 상세사항으로 기재되지 않는다. "한 가지 구체예" 또는 "구체예"에 대한 본 명세서 전체를 통한 참조는 구체예와 결부되어 기재된 특별한 특징, 형태, 조성 또는 특성이 본 발명의 하나 이상의 구체예에 포함됨을 의미한다. 따라서, 본 명세서 전체에 걸친 다양한 위치에서 표현된 "한 가지 구체예에서" 또는 "구체예"의 상황은 반드시 본 발명의 동일한 구체예를 나타내지는 않는다. 추가로, 특별한 특징, 형태, 조성, 또는 특성은 하나 이상의 구체예에서 어떠한 적합한 방법으로 조합될 수 있다.Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, for a thorough understanding of the present invention, various specific details are described, such as specific forms, compositions, processes and the like. However, certain embodiments may be practiced without one or more of these specific details, or in conjunction with other known methods and forms. In other instances, well known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "embodiment" means that a particular feature, form, composition or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Accordingly, the appearances of the phrase " in one embodiment "or" an embodiment "in various places throughout this specification are not necessarily indicative of the same embodiment of the present invention. In addition, particular features, forms, compositions, or properties may be combined in any suitable manner in one or more embodiments.
본 발명의 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 약제학적 조성물을 제공하는 것이다. One object of the present invention is to provide a pharmaceutical composition for wound treatment comprising liquid plasma and growth factors as an active ingredient.
본 발명의 다른 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 의약외품 조성물을 제공하는 것이다.Another object of the present invention to provide a quasi-drug composition for wound treatment comprising a liquid plasma and growth factors as an active ingredient.
본 발명의 또 다른 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention to provide a health care food composition for wound treatment comprising a liquid plasma and growth factors as an active ingredient.
본 발명의 또 다른 하나의 목적은 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 조성물을 개체에 투여하는 단계를 포함하는 상처 치료 방법을 제공하는 것이다.Yet another object of the present invention is to provide a wound healing method comprising administering to a subject a composition comprising a liquid plasma and a growth factor as an active ingredient.
본 발명의 또 다른 하나의 목적은 액상 플라즈마 및 성장인자을 유효성분으로 포함하는 조성물을 개체의 피부에 도포하는 단계를 포함하는, 상처 치료 방법을 제공하는 것이다.Yet another object of the present invention is to provide a wound healing method comprising applying to the skin of an individual a composition comprising a liquid plasma and a growth factor as an active ingredient.
본 명세서에서 사용된 용어 "액상 플라즈마(non thermal plasma treated solution, NTS)"는 고밀도 고에너지 플라즈마를 액체 속에서 발생시키는 것을 의미하며, 대기압의 상온 비열 플라즈마(nonthermal plasma, NTP)에 노출시켜 제조될 수 있다. 상기 용어 “액상 플라즈마”는 용어 “플라즈마 처리된 액상 물질(plasma-conditioned liquid material)"과 상호교환적으로 사용될 수 있고, 상기의 “액상 물질”은 액상 형태의 물질은 제한없이 사용 가능하나, 바람직하게는 물, 식염수, 완충액, 또는 배지이고, 가장 바람직하게는 배지이다.As used herein, the term "non thermal plasma treated solution (NTS)" refers to the generation of high density high energy plasma in a liquid, which can be prepared by exposure to atmospheric nonthermal plasma (NTP) at atmospheric pressure. Can be. The term "liquid plasma" may be used interchangeably with the term "plasma-conditioned liquid material" and the term "liquid material" may be used without limitation in the form of a liquid, but preferably Preferably water, saline, buffer, or medium, most preferably medium.
본 명세서에서 사용된 용어 "배지(culture media)"는 인 비트로(in vitro)에서 세포 성장 및 생존을 지지할 수 있게 하는 배지를 의미하고, 세포의 배양에 적절한 당 분야에서 사용되는 통상의 배지를 모두 포함한다. 세포의 종류에 따라 배지와 배양조건을 선택할 수 있다. 세포의 배양에 사용되는 기본배지는 바람직하게는 세포 배양 최소 배지(cell culture minimum medium: CCMM)로, 일반적으로 탄소원, 질소원 및 미량원소 성분을 포함한다. 이런 세포 배양 기본 배지에는 예를 들면, DMEM(Dulbeco's Modified Eagle's Medium), MEM(Minimal essential Medium), BME(Basal Medium Eagle), RPMI1640, F-10, F-12,(Minimal essential Medium), GMEM(Glasgow's Minimal essential Medium), Iscove's Modified Dulbecco's Medium 등이 있으나, 이로 제한되지 않는다.As used herein, the term "culture media" refers to a medium capable of supporting cell growth and survival in vitro , and refers to a conventional medium used in the art appropriate for the culture of cells. It includes everything. Depending on the type of cells, medium and culture conditions can be selected. The basal medium used for culturing the cells is preferably a cell culture minimum medium (CCMM), and generally includes a carbon source, a nitrogen source and a trace element component. Such cell culture basal media include, for example, Dulbeco's Modified Eagle's Medium (DMEM), Minimal Essential Medium (MEM), Basic Medium Eagle (BME), RPMI1640, F-10, F-12, (Minimal Essential Medium), GMEM ( Glasgow's Minimal Essential Medium), Iscove's Modified Dulbecco's Medium, but are not limited to these.
본 명세서에서 사용된 용어 "성장인자"는 여러 세포의 분열, 성장 및 분화를 촉진하는 폴리펩티드를 의미하며, 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)를 포함하나, 이에 제한되는 것은 아니다.As used herein, the term "growth factor" refers to a polypeptide that promotes the division, growth and differentiation of several cells, and refers to epidermal growth factor (EGF), platelet derived growth factor-AA (PDGF-AA), insulin-like growth Factor-1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblast growth factor (FGF), but is not limited thereto.
본 명세서에서 사용된 용어 "치료"는 본 발명에 따른 액상 플라즈마를 이용하여 상처 또는 이로 인한 질환의 증세를 호전시키거나 이롭게 변경하는 모든 행위를 의미한다. 본원이 속하는 기술분야에서 통상의 지식을 가진 자라면, 대한의학협회 등에서 제시된 자료를 참조하여 상처의 정확한 기준을 파악하고, 개선, 향상 및 치료된 정도를 판단할 수 있을 것이다.As used herein, the term "treatment" means any action that improves or advantageously alters the symptoms of a wound or a resulting disease using the liquid plasma according to the present invention. Those skilled in the art to which the present application belongs, will be able to determine the exact criteria of the wound, and determine the degree of improvement, improvement and treatment with reference to the data presented by the Korean Medical Association.
본 명세서에 있어서 “약학조성물”이란, 특정한 목적을 위해 투여되는 조성물을 의미한다. 본 발명의 목적상, 본 발명의 약학조성물은 플라즈마를 액상 물질에 조사하여 제조한 액상 플라즈마를 유효성분으로 포함하는 것이며, 이에 관여하는 단백질 및 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함할 수 있다. 상기의 "약학적 허용될 가능한" 담체 또는 부형제는 정부의 규제부에 의해 승인된 것이나, 또는 척추 동물, 그리고 보다 특별하게는 인간에게 사용을 위한 정부 또는 기타 일반적으로 승인된 약전에서 리스트된 것을 의미한다.As used herein, the term "pharmaceutical composition" means a composition to be administered for a specific purpose. For the purposes of the present invention, the pharmaceutical composition of the present invention includes a liquid plasma prepared by irradiating a plasma to a liquid substance as an active ingredient, and may include a protein and a pharmaceutically acceptable carrier, excipient or diluent involved therein. have. Said "pharmaceutically acceptable" carrier or excipient means that which has been approved by the governmental regulatory authority, or listed in government or other generally approved pharmacopoeia for use in vertebrates, and more particularly in humans. do.
비경구적인 투여를 위해 본 발명의 약학조성물은 유성 또는 수성 담체에 있는 현탁액, 용액 또는 에멀젼의 형태로 될 수 있고, 고체 또는 반고체의 형태로 제조될 수 있다. 또한, 본 발명의 약학조성물은 현탁제, 안정화제, 용해제 및/또는 분산제와 같은 제형화제를 포함할 수 있고, 멸균될 수 있다. 상기 약학조성물은 제조 및 저장의 조건 하에서 안정할 수 있고, 세균이나 곰팡이와 같은 미생물의 오염 작용에 대해 보존될 수 있다. 대안적으로, 본 발명의 약학조성물은 사용 전에 적절한 담체와 재구성을 위해 멸균 분말 형태일 수 있다. 약학조성물은 단위-복용량 형태로, 마이크로니들 패치에, 앰플에, 또는 기타 단위-복용량 용기에, 또는 다-복용량 용기에 존재할 수 있다. 대안적으로, 약학적 조성물은 단지 멸균 액체 담체, 예를 들어 사용 바로 전에 주사용 물의 부가함을 요하는 동결-건조된(냉동건조) 상태로 보관될 수 있다. 즉시 주사용액 및 현탁액은 멸균 분말, 그래뉼 또는 타블렛으로 제조될 수 있다.For parenteral administration, the pharmaceutical compositions of the invention may be in the form of suspensions, solutions or emulsions in oily or aqueous carriers, and may be prepared in the form of solids or semisolids. In addition, the pharmaceutical compositions of the present invention may include formulating agents such as suspending, stabilizing, dissolving and / or dispersing agents and may be sterilized. The pharmaceutical composition may be stable under the conditions of manufacture and storage, and may be preserved against the contaminating action of microorganisms such as bacteria or fungi. Alternatively, the pharmaceutical compositions of the present invention may be in sterile powder form for reconstitution with a suitable carrier prior to use. The pharmaceutical compositions may be in unit-dose form, in microneedle patches, in ampoules, or in other unit-dose containers, or in multi-dose containers. Alternatively, the pharmaceutical composition may be stored in a freeze-dried (freeze-dried) state, which requires the addition of a sterile liquid carrier, eg, water for injection just before use. Immediately injectable solutions and suspensions may be prepared as sterile powders, granules or tablets.
몇몇 비 제한적인 실시형태에 있어서, 본 발명의 약학조성물은 제형화되어 질 수 있고, 또는 액체 속에 미립구의 형태로 포함될 수 있다. 어떤 비 제한적인 실시형태에 있어서, 본 발명의 약학조성물은 이들의 약학적으로 허용될 수 있는 화합물 및/또는 혼합물을 0.001 내지 100,000 U/kg 사이의 농도로 포함할 수 있다. 또한 어떤 비 제한적인 실시형태에 있어서, 본 발명의 약학조성물은 적절한 부형제는 보존제, 현탁제, 추가적인 안정화제, 염료, 완충제, 항균제, 항진균제, 및 등장화제, 예를 들어, 설탕 또는 염화나트륨을 포함할 수 있다. 여기서 사용된 것으로, 용어 "안정화제"는 보존 수명을 증가하기 위해 본 발명의 약학조성물에 선택적으로 사용된 화합물을 언급한다. 비-제한적인 실시에 있어서, 안정화제는 당, 아미노산, 또는 폴리머일 수 있다. 또한 본 발명의 약학조성물은 하나 또는 그 이상의 약학적으로 허용될 수 있는 담체를 포함할 수 있고, 상기 담체는 용매 또는 분산 배지일 수 있다. 약학적으로 허용될 수 있는 담체의 비-제한적인 예는 물, 식염수, 에탄올, 폴리올 (예, 글리세롤, 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜), 오일, 및 이들의 적절한 혼합물을 포함한다. 본 발명의 약학조성물에 적용되는 멸균 기술의 비-제한적인 예는 세균-억제 필터를 통한 여과, 터미날 멸균화, 멸균 제제의 합체, 방사선 조사, 멸균 가스 조사, 가열, 진공 건조 및 동결 건조를 포함한다.In some non-limiting embodiments, the pharmaceutical compositions of the present invention can be formulated or included in the form of microspheres in a liquid. In certain non-limiting embodiments, the pharmaceutical compositions of the present invention may comprise their pharmaceutically acceptable compounds and / or mixtures at concentrations between 0.001 and 100,000 U / kg. Also in certain non-limiting embodiments, the pharmaceutical compositions of the present invention may include suitable excipients, preservatives, suspending agents, additional stabilizers, dyes, buffers, antibacterial agents, antifungal agents, and isotonic agents, for example, sugars or sodium chloride. Can be. As used herein, the term "stabilizer" refers to a compound that is optionally used in the pharmaceutical compositions of the present invention to increase shelf life. In a non-limiting implementation, the stabilizer can be a sugar, an amino acid, or a polymer. In addition, the pharmaceutical composition of the present invention may include one or more pharmaceutically acceptable carriers, and the carrier may be a solvent or a dispersion medium. Non-limiting examples of pharmaceutically acceptable carriers include water, saline, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycols), oils, and suitable mixtures thereof. Non-limiting examples of sterilization techniques applied to the pharmaceutical compositions of the present invention include filtration through bacteria-inhibiting filters, terminal sterilization, incorporation of sterile preparations, irradiation, sterile gas irradiation, heating, vacuum drying and freeze drying. do.
본 명세서에 있어서 “투여”란, 어떠한 적절한 방법으로 환자에게 본 발명의 조성물을 도입하는 것을 의미하며, 본 발명의 조성물의 투여경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 경구 투여, 복강 내 투여, 정맥 내 투여, 근육 내 투여, 피하 투여, 피내 투여, 비내 투여, 폐내 투여, 직장내 투여, 강내 투여, 복강 내 투여, 경막 내 투여가 이루어질 수 있으나, 본 발명의 약학조성물은 피부 위에 도포하거나 피하 또는 피내에 주사하는 형태로 제공되는 것이 가장 바람직하나, 이에 제한되는 것은 아니다.As used herein, "administration" means introducing the composition of the present invention to a patient in any suitable manner, and the route of administration of the composition of the present invention may be administered via any general route as long as it can reach the desired tissue. have. Oral administration, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, intranasal administration, pulmonary administration, rectal administration, intraluminal administration, intraperitoneal administration, intradural administration, The composition is most preferably provided in the form of an application on the skin or subcutaneous or intradermal injection, but is not limited thereto.
본 발명의 치료 방법은 상기 약학조성물을 약제학적 유효량으로 투여하는 것을 포함할 수 있다. 본 발명에서 유효량은 질환의 종류, 질환의 중증도, 조성물에 함유된 유효 성분 및 다른 성분의 종류 및 함량, 제형의 종류 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료 기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다.The method of treatment of the present invention may comprise administering the pharmaceutical composition in a pharmaceutically effective amount. In the present invention, the effective amount is defined as the type of disease, the severity of the disease, the type and amount of the active ingredient and other ingredients contained in the composition, the type and formulation of the patient and the age, body weight, general health condition, sex and diet, time of administration, route of administration And various factors, including the rate of secretion of the composition, the duration of treatment, and the drugs used concurrently.
본 발명의 일 구체예에서, (a) 플라즈마 발생 장치에 캐리어 가스를 충진하는 단계; (b) 상기 플라즈마 발생 장치에 5kV 내지 20kV의 전압 및 10 내지 30kHz의 주파수를 공급하여 플라즈마를 발생시키는 단계; 및 (c) 상기 발생된 플라즈마를 액상 물질에 조사하는 단계를 포함하는 상처 치료용 액상 플라즈마 제조 방법을 제공하고, 상기 (a) 단계에서의 캐리어 가스는 질소, 헬륨, 아르곤, 및 산소로 구성되는 그룹으로부터 선택되는 어느 하나 이상인 것을 특징으로 하는 상처 치료용 액상 플라즈마 제조 방법을 제공하며, 상기 캐리어 가스는 질소인 것을 특징으로 하는 상처 치료용 액상 플라즈마 제조 방법을 제공하며, 상기 (b) 단계에서의 조사는 액상 물질의 표면으로부터 0.1cm 내지 15cm 떨어진 거리에서 1㎖당 1분간 수행하는 것을 특징으로 하는 것인 상처 치료용 액상 플라즈마 제조 방법을 제공하며, 상기 (c) 단계에서의 액상 물질은 물, 식염수, 완충액, 또는 배지인 상처 치료용 액상 플라즈마 제조 방법을 제공한다.In one embodiment of the present invention, (a) filling the plasma generating apparatus with a carrier gas; (b) generating a plasma by supplying a voltage of 5 kV to 20 kV and a frequency of 10 to 30 kHz to the plasma generator; And (c) irradiating the generated plasma to a liquid material, wherein the liquid plasma manufacturing method for treating a wound is provided, wherein the carrier gas in step (a) is composed of nitrogen, helium, argon, and oxygen. It provides a liquid plasma manufacturing method for wound treatment, characterized in that any one or more selected from the group, the carrier gas provides a liquid plasma manufacturing method for wound treatment, characterized in that the nitrogen, in the step (b) Irradiation is a liquid plasma manufacturing method for wound treatment, characterized in that performed for 1 minute per 1 ml at a distance from 0.1cm to 15cm from the surface of the liquid material, the liquid material in step (c) is water, Provided are a method for preparing a liquid plasma for wound treatment, which is saline, buffer, or a medium.
본 발명의 다른 구체예에서, 상기 중 어느 하나 이상의 방법으로 제조된 액상 플라즈마를 유효성분으로 포함하는 상처 치료용 약학조성물을 제공하고, 상기 약학조성물은 성장인자를 추가로 포함하는 상처 치료용 약학조성물을 제공하며, 상기 성장인자는 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)인 것인 상처 치료용 약학조성물을 제공하며, 상기 성장인자는 상피세포 성장인자(EGF)인 상처 치료용 약학조성물을 제공하며, 상기 상처는 자상, 박피, 발진, 염증, 궤양, 또는 스크레치에 의한 피부 손상인 상처 치료용 약학조성물을 제공하며, 상기 약학조성물은 피부 외용제의 형태로 제공되는 것인 상처 치료용 약학조성물을 제공하며, 상기 약학조성물은 액제, 연고제, 크림제, 로션제, 스프레이제, 패취제, 겔제 또는 에어로졸제인 것인 상처 치료용 약학조성물을 제공한다.In another embodiment of the present invention, there is provided a pharmaceutical composition for wound treatment comprising the liquid plasma prepared by any one or more of the above method as an active ingredient, wherein the pharmaceutical composition is a wound composition for the pharmaceutical composition further comprising a growth factor Wherein the growth factor is epithelial growth factor (EGF), platelet-derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β) Or fibroblast growth factor (FGF), which provides a pharmaceutical composition for treating wounds, wherein the growth factor is epithelial growth factor (EGF), and the wound is wound, peeling, rash. Provides a pharmaceutical composition for treating wounds, which are skin damage caused by inflammation, ulcers, or scratches, wherein the pharmaceutical composition provides a pharmaceutical composition for treating wounds, which is provided in the form of an external preparation for skin. Provides a pharmaceutical composition for the wounds of liquids, ointments, creams, lotions, spray agents, will paechwije, gels or aerosol therapeutic agent.
본 발명의 또 다른 구체예에서, 상기 중 어느 하나 이상의 방법으로 제조된 액상 플라즈마 및 성장인자를 유효성분으로 포함하는 상처 치료용 의약외품 조성물을 제공하고, 상기 성장인자는 상피세포 성장인자(EGF), 혈소판 유래 성장인자-AA(PDGF-AA), 인슐린 유사 성장인자-1(IGF-1), 형질 전환 성장인자-β(TGF-β) 또는 섬유아세포 성장인자(FGF)인 것인 상처 치료용 의약외품 조성물을 제공한다.In another embodiment of the present invention, there is provided a quasi-drug composition for wound treatment comprising a liquid plasma and a growth factor prepared by any one or more of the above method as an active ingredient, wherein the growth factor is epithelial cell growth factor (EGF), A drug for the treatment of wounds, which is platelet-derived growth factor-AA (PDGF-AA), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β) or fibroblast growth factor (FGF) To provide a composition.
이하 상기 본 발명을 단계별로 상세히 설명한다.Hereinafter, the present invention will be described in detail step by step.
본 발명에 따른 액상 플라즈마 및 성장인자를 포함하는 조성물은 섬유아세포의 재생을 촉진시킬 수 있다. 따라서, 본 발명에 따른 액상 플라즈마 및 성장인자를 포함하는 조성물은 상처의 치유를 촉진시킬 수 있을 것으로 기대된다. The composition comprising a liquid plasma and a growth factor according to the present invention can promote the regeneration of fibroblasts. Therefore, it is expected that the composition comprising the liquid plasma and the growth factor according to the present invention can promote the healing of wounds.
도 1은 본 발명에 따른 액상 플라즈마(NTS)의 제조방법을 나타낸 도면이다.
도 2는 본 발명의 실험예 1에 따른 결과를 나타낸다.
도 3은 본 발명의 실험예 2에 따른 결과를 나타낸다.1 is a view showing a method for manufacturing a liquid plasma (NTS) according to the present invention.
2 shows the results according to Experimental Example 1 of the present invention.
3 shows the results according to Experimental Example 2 of the present invention.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
<실시예><Examples>
실시예 1. 액상 플라즈마(NTS) 및 성장인자를 포함하는 조성물의 제조Example 1 Preparation of a Composition Comprising Liquid Plasma (NTS) and Growth Factor
본 발명에 따른 액상 플라즈마와 성장인자의 상처 치료에 미치는 효과를 알아보기 위하여, 배지로서 DMEM High Glucose + 10 % FBS 및 성장인자로서 EGF를 이용하여 섬유아세포에서 세포 이동(cell migration) 효과를 평가하였다. 우선 전압 15kV 및 주파수 15kHz의 전원이 공급되고 캐리어 가스로는 질소 가스를 이용하는 플라즈마 발생장치를 이용하여 상기 배지에 플라즈마를 처리하여 액상 플라즈마("플라즈마 처리된 배지")를 완성하였다. 상기 액상 플라즈마의 제조방법을 도 1에 나타내었다.In order to examine the effect of liquid plasma and growth factor on wound healing according to the present invention, the effect of cell migration in fibroblasts was evaluated using DMEM High Glucose + 10% FBS as a medium and EGF as a growth factor. . First, power was supplied at a voltage of 15 kV and a frequency of 15 kHz, and the plasma was treated with a plasma generator using nitrogen gas as a carrier gas to complete a liquid plasma (“plasma treated medium”). The method of manufacturing the liquid plasma is shown in FIG. 1.
<실험예><Experimental Example>
실험예 1. 본 발명에 따른 조성물의 상처 치료 효과Experimental Example 1. Wound healing effect of the composition according to the invention
상기 실시예 1에서 제조된 액상 플라즈마에 EGF를 각각 10ng/ml 및 30ng/ml 양으로 pretreat 하고, 사람 유래의 섬유아세포(Fibroblast) 세포주(1X105 cell)를 seeding하여 1시간 후에 세포 이동 결과를 wound healing assay로 평가하였다. 한편, 비교예로서 액상 플라즈마 및 EGF 각각에 섬유아세포를 seeding한 후 세포 이동을 확인하였다. 그 결과를 도 2에 나타내었다. Pretreat EGF in amounts of 10 ng / ml and 30 ng / ml, respectively, in the liquid plasma prepared in Example 1, and seed the human-derived fibroblast cell line (1 × 10 5 cells) to wound the cell migration result after 1 hour. It was evaluated by a healing assay. On the other hand, as a comparative example, after seeding the fibroblasts in each of the liquid plasma and EGF, cell migration was confirmed. The results are shown in Fig.
도 2를 참고하면, 비교예로서 액상 플라즈마만을 단독 처리한 군에서는 상처 치료 효과가 나타나지 않았지만, EGF만을 단독 처리한 군에서는 상처 치료 효과가 확인되었다. 액상 플라즈마 및 EGF를 모두 처리한 군에서는 EGF만을 단독 처리하였을 때보다 현저한 상처 치료 효과가 확인되었다. Referring to FIG. 2, as a comparative example, the wound treatment effect was not observed in the group treated with only liquid plasma, but the wound treatment effect was confirmed in the group treated with EGF alone. In the group treated with both liquid plasma and EGF, a significant wound healing effect was observed than when treated with EGF alone.
실험예 2. 본 발명에 따른 조성물의 cytotoxicity 확인Experimental Example 2. Confirmation of cytotoxicity of the composition according to the present invention
본 발명에 따른 액상 플라즈마 및 EGF를 포함하는 조성물이 섬유아세포에 cytotoxicity를 나타내는지 알아보기 위하여 cell viability 결과를 MTT로 확인하였다. 그 결과를 도 3에 나타내었다. In order to determine whether the composition comprising the liquid plasma and EGF according to the present invention exhibits cytotoxicity in fibroblasts, the cell viability result was confirmed by MTT. The results are shown in Fig.
도 3을 참고하면, 본 발명에 따른 조성물이 섬유아세포 cytotoxicity는 없는 것으로 확인되었다. Referring to Figure 3, it was confirmed that the composition according to the present invention is not fibroblast cytotoxicity.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far I looked at the center of the preferred embodiment for the present invention. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.
Claims (9)
(b) 상기 플라즈마 발생 장치에 15kV의 전압 및 15kHz의 주파수를 공급하여 플라즈마를 발생시키는 단계;
(c) 상기 발생된 플라즈마를 액상 물질에 조사하는 단계를 포함하여 액상 플라즈마를 제조하는 단계; 및
상기 액상 플라즈마에 상피세포 성장인자(EGF)를 처리하는 단계를 포함하고,
상기 (a) 단계에서의 캐리어 가스는 질소인 것을 특징으로 하는, 상처 치료용 약학 조성물의 제조 방법.
(a) filling a carrier gas into a plasma generating device;
(b) generating a plasma by supplying a voltage of 15 kV and a frequency of 15 kHz to the plasma generator;
(c) preparing a liquid plasma, comprising irradiating the generated plasma to a liquid material; And
Treating epithelial cell growth factor (EGF) in the liquid plasma;
The carrier gas in the step (a) is characterized in that the nitrogen, method for producing a pharmaceutical composition for wound treatment.
상기 (c) 단계에서의 액상 물질은 물, 식염수, 완충액, 또는 배지인, 상처 치료용 약학 조성물의 제조 방법.
The method of claim 1,
The liquid material in step (c) is water, saline, buffer, or a medium, the method of preparing a pharmaceutical composition for wound treatment.
(a) filling a carrier gas into a plasma generating device; (b) generating a plasma by supplying a voltage of 15 kV and a frequency of 15 kHz to the plasma generator; And (c) irradiating the generated plasma to a liquid material, wherein the liquid plasma is prepared, and epithelial growth factor (EGF) as an active ingredient, wherein the carrier gas is nitrogen. Therapeutic pharmaceutical composition.
상기 상처는 자상, 박피, 발진, 염증, 궤양, 또는 스크레치에 의한 피부 손상인, 상처 치료용 약학조성물.
5. The method of claim 4,
The wound is wound, skin peeling, rash, inflammation, ulcers, or damage to the skin by scratch, pharmaceutical composition for wound treatment.
(a) filling a carrier gas into a plasma generating device; (b) generating a plasma by supplying a voltage of 15 kV and a frequency of 15 kHz to the plasma generator; And (c) irradiating the generated plasma to a liquid material, wherein the liquid plasma is prepared, and epithelial growth factor (EGF) as an active ingredient, wherein the carrier gas is nitrogen. Therapeutic quasi-drug composition.
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| US16/464,180 US11759407B2 (en) | 2016-11-25 | 2017-11-13 | Composition for skin whitening or wound treatment, containing liquid plasma |
| PCT/KR2017/012771 WO2018097527A1 (en) | 2016-11-25 | 2017-11-13 | Composition for skin whitening or wound treatment, containing liquid plasma |
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| KR20210055949A (en) | 2019-11-08 | 2021-05-18 | 주식회사 엠마헬스케어 | A wound-healing dressing patch using cold plasma and low level laser |
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| KR101101321B1 (en) * | 2008-11-03 | 2012-01-02 | 주식회사 엠씨티티 | cell delivery vehicle composition having a hydrogel form for healing wounds |
| WO2015191843A1 (en) * | 2014-06-13 | 2015-12-17 | Advanced Plasma Therapies, Inc. | Veterinary methods for using nitric oxide in a plasma state to treat medical conditions and diseases in animals |
| KR101657063B1 (en) * | 2015-04-09 | 2016-09-13 | 아주대학교산학협력단 | Liquid type plasma for preventing and treating of cancer |
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| KR101101321B1 (en) * | 2008-11-03 | 2012-01-02 | 주식회사 엠씨티티 | cell delivery vehicle composition having a hydrogel form for healing wounds |
| WO2015191843A1 (en) * | 2014-06-13 | 2015-12-17 | Advanced Plasma Therapies, Inc. | Veterinary methods for using nitric oxide in a plasma state to treat medical conditions and diseases in animals |
| KR101657063B1 (en) * | 2015-04-09 | 2016-09-13 | 아주대학교산학협력단 | Liquid type plasma for preventing and treating of cancer |
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| KR20210055949A (en) | 2019-11-08 | 2021-05-18 | 주식회사 엠마헬스케어 | A wound-healing dressing patch using cold plasma and low level laser |
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