KR101987783B1 - Biodegradable polymeric microparticle and method for preparing the same, and biodegradable polymeric filler comprising the same - Google Patents
Biodegradable polymeric microparticle and method for preparing the same, and biodegradable polymeric filler comprising the same Download PDFInfo
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
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- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
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- C08J3/00—Processes of treating or compounding macromolecular substances
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Abstract
본 발명은 생분해성 고분자 미립자 및 그 제조방법, 및 이를 포함하는 생분해성 고분자 필러에 관한 것으로서, 보다 상세하게는, 생분해성 고분자 코어 및 상기 코어 표면상에 코팅된 콜라겐 유도 물질을 포함하며, 생체에 필러로 적용시 시술 초기 볼륨감소를 막고 히알루론산 필러보다 긴 유지기간을 동시에 총족시킬 수 있는 생분해성 고분자 미립자 및 그 제조방법, 및 이를 포함하는 생분해성 고분자 필러에 관한 것이다.The present invention relates to a biodegradable polymeric microparticle, a method for producing the biodegradable polymeric microparticle, and a biodegradable polymeric filler comprising the biodegradable polymeric microparticle. More particularly, the present invention relates to a biodegradable polymeric core and a collagen- The present invention relates to a biodegradable polymeric microparticle capable of preventing a decrease in volume at the initial stage of treatment when applied as a filler and having a longer maintenance period than that of a hyaluronic acid filler at the same time, a method for producing the same, and a biodegradable polymeric filler comprising the biodegradable polymeric filler.
Description
본 발명은 생분해성 고분자 미립자 및 그 제조방법, 및 이를 포함하는 생분해성 고분자 필러에 관한 것으로서, 보다 상세하게는, 생분해성 고분자 코어 및 상기 코어 표면상에 코팅된 콜라겐 유도 물질을 포함하며, 생체에 필러로 적용시 시술 초기 볼륨감소를 막고 히알루론산 필러보다 긴 유지기간을 동시에 충족시킬 수 있는 생분해성 고분자 미립자 및 그 제조방법, 및 이를 포함하는 생분해성 고분자 필러에 관한 것이다.The present invention relates to a biodegradable polymeric microparticle, a method for producing the biodegradable polymeric microparticle, and a biodegradable polymeric filler comprising the biodegradable polymeric microparticle. More particularly, the present invention relates to a biodegradable polymeric core and a collagen- The present invention relates to a biodegradable polymeric microparticle capable of preventing a decrease in volume at the initial stage of treatment when applied as a filler and meeting a longer maintenance period than a hyaluronic acid filler at the same time, a method for producing the biodegradable polymeric microparticle, and a biodegradable polymeric filler containing the same.
질병의 퇴치를 목표로 하는 시대, 더 오래 살고자 하는 욕구를 실현하기 위해 노력하던 시대, 이와 더불어 건강하게 살고자 노력하는 시대가 지나면서, 최근에는 젊고 아름답게 살고자 하는 세태를 반영한 시대가 도래하였다.In the era aiming at the eradication of disease, in the age of trying to realize the desire to live longer, and in the age of trying to live healthily with it, the era has come to reflect the situation of living young and beautiful recently .
노화는 모든 인간이 보편적, 필수적으로 겪는 생명 현상으로, 수명이 연장됨에 따라서 안티에이징(anti-aging) 분야에 대한 관심이 집중되고 있으며, 최근에는 노화 복구보다 사전 예방이 효과적이라는 인식하에 젊은 세대부터 안티에이징에 대한 수요가 급증하고 있다. 즉, 젊음과 아름다움을 추구하는 안티에이징 트렌드가 빠르게 확산되면서 미의 개념도 화려함에서 젊음으로 진화하고 있다.Aging is a universal and essential life phenomenon of all human beings. As life spans are prolonged, interest in anti-aging has been focused. In recent years, young people Demand for anti-aging is increasing rapidly. In other words, as anti-aging trends that pursue youth and beauty are rapidly spreading, the concept of beauty also evolves from glamor to youth.
피부 치료, 기능성 화장품, 필러 및 보툴리눔 톡신, 미용 서비스 등 안티에이징 산업 고객층이 2000년 이후 고소득자나 연예인 등 미용에 관심이 높은 사람에게서 중산층과 일반 대중으로 확대되고 있으며, 수명 연장, 웰빙 트렌드, 바이오 기술의 발전으로 안티에이징에 대한 관심이 사회전반에 걸쳐 증가하고 있다. 학계는 노화 과정을 늦추는 기술로, 의료계는 노인성 질환의 진단 및 치료로, 산업계는 어려 보이게 하는 제품과 서비스로 각각 활용되고 있다.Since 2000, anti-aging industry customers such as skin care, functional cosmetics, fillers and botulinum toxins and beauty services have been expanding from middle-class and general public to those who are interested in beauty such as high-income earners and entertainers. The interest in anti-aging has been increasing throughout society. The academic world is a technology that slows down the aging process. The medical industry is used as diagnosis and treatment for geriatric diseases, and the products are used as products and services that make the industry harder.
안티에이징 시장은 화장품 등의 소비재 분야, 의료 분야, 서비스 분야 등으로 나눌 수 있다. 의료 분야는 보툴리눔 톡신, 히알루론산 필러 등 관련 의약품과 생체 재료가 다수 개발되면서 성장을 견인하고 있다. 근육이완 효과로 사시치료에 사용되던 보톨리눔 톡신의 경우 우리나라 의료기관의 미용 목적 사용이 90%에 달하고 있고, 히알루론산, 콜라겐 등 안전하면서도 생체흡수가 빠른 의약 재료도 상용화되면서 필러 시장도 빠르게 성장하고 있다.The anti-aging market can be divided into consumer goods such as cosmetics, medicine, and service. In the medical field, many drugs and biomaterials such as botulinum toxin and hyaluronic acid filler have been developed, leading to growth. In the case of botulinum toxin, which has been used for the treatment of strabismus due to muscle relaxation effect, the beauty purpose of the medical institution in Korea has reached 90%, and the filler market is also growing rapidly as safe materials such as hyaluronic acid, collagen etc. .
빠르게 성장하고 있는 필러 제품의 발전은 4세대로 구분할 수 있다.The development of fast-growing filler products can be divided into four generations.
제1세대는 콜라겐(collagen)을 사용한 필러로서 과거에는 가장 광범위하게 사용되기도 하였으나, 실질적으로 1~3개월에 불과한 짧은 유지기간과 소 유래 콜라겐이 유발하는 알러지 등의 부작용으로 인해 이미 쇠퇴기에 있는 제품이다.The first generation is a collagen-based filler, which has been used most extensively in the past, but it is a product that is already in decline due to side effects such as a short maintenance period of only 1 to 3 months and collagen- to be.
제2세대는 히알루론산(HA) 필러로서 현재 필러 시장에서 90%의 시장점유율을 가지고 있는 성장기의 제품이다. 히알루론산은 생체적합성이 있고 독성이 없어 필러 소재로서 우수한 특성이 있으나, 1년을 채우기 어려운 비교적 짧은 체내 유지기간이 단점으로 지적되고 있어, 기존 히알루론산 필러 제조업체들이 생체 내에서의 흡수 속도를 늦추기 위한 노력을 지속적으로 기울이고 있다. 그러나 유지기간을 늘리기 위해 히알루론산의 가교도를 높일 경우, 즉, 가교제를 많이 사용하게 될 경우 가교제 자체의 독성으로 인해 생체적합성이 떨어지게 되는 부작용이 있어 가교제를 적게 쓰면서도 가교도를 높여야 하는 기술적 도전을 요구받고 있는 실정이다.The second generation is hyaluronic acid (HA) filler, which is a growing product with 90% market share in the filler market. Although hyaluronic acid is biocompatible and has no toxicity, it has excellent properties as a filler material. However, it is pointed out as a disadvantage in relatively short duration of body maintenance that it is difficult to fill a year, so that existing hyaluronic acid filler manufacturers We are continually devoting our efforts. However, when increasing the degree of crosslinking of hyaluronic acid to increase the maintenance period, that is, when the crosslinking agent is used in a large amount, there is a side effect that the biocompatibility is deteriorated due to the toxicity of the crosslinking agent itself. Thus, a technical challenge is required to increase the degree of crosslinking while using less crosslinking agent In fact.
칼슘이나 폴리메틸메타크릴레이트(PMMA) 등을 이용한 제3세대 필러는 생분해되지 않아 반영구적이라는 장점이 안전성에 문제가 발생하자 단점으로 돌변하면서 성장기로 접어들지 못하고 시장에 출현하자마자 퇴출 위기에 놓였다.The third-generation filler using calcium or polymethylmethacrylate (PMMA) has not been biodegraded and has a semi-permanent advantage. As a result of safety problems, it has turned into a disadvantage.
그 뒤를 이어서 제4세대 필러로서 생분해성 고분자 필러가 시장에 등장하여 성장기에 진입하고 있다. 국제공개특허 WO 1998/56431, WO 2009/014441 등에는 PLA, PCL 등의 생분해성 고분자를 이용한 필러가 개시되어 있으며, 실제로 이 공개특허들에 개시된 필러를 이용한 상용 제품이 출시되어 있다. 생분해성 고분자 필러는 제품 자체의 부피로 피부 조직을 지지하는 기존 히알루론산 필러와 달리 고분자가 생분해되면서 자가 콜라겐 생성을 유도하여 조직을 지지하고 주름을 펴지게 하는 기전으로, 볼륨이 자연스럽고 히알루론산 필러보다 유지기간이 길다는 장점이 있으나, 시술 후 1주일 이내에 초기 볼륨이 대폭 감소했다가 이후 6주~6개월에 걸쳐 서서히 볼륨이 재발현되는 지효성이라는 것이 시장 확대의 가장 큰 걸림돌로 알려지고 있다.Followed by biodegradable polymer fillers as fourth-generation fillers are entering the market. International patent publications WO 1998/56431 and WO 2009/014441 disclose fillers using biodegradable polymers such as PLA and PCL, and commercially available products using the fillers disclosed in these patents have been put on the market. Biodegradable polymer filler is a volume of the product itself, unlike conventional hyaluronic acid filler that supports skin tissue, biodegrades polymer to induce self collagen production to support tissue and wrinkle spreading, volume is natural, hyaluronic acid filler Although it has the advantage of a longer maintenance period, it is known that the initial volume is greatly reduced within one week after the procedure, and that the volume is gradually re-expressed over a period of 6 to 6 months.
그러므로 자가 콜라겐 생성을 유도하고 체내 유지기간이 긴 생분해성 고분자 소재이면서도 기존 히알루론산 필러처럼 시술 직후부터 볼륨을 발현하는 새로운 고분자 필러에 대한 요구가 충족되지 않고 있는 실정이며, 이를 타개하기 위한 더 많은 연구개발이 필요하다.Therefore, even though it is a biodegradable polymer material that induces self-collagen production and has a long period of maintenance in the body, the demand for a new polymer filler expressing volume from the time immediately after the procedure like a conventional hyaluronic acid filler is not satisfied, Development is needed.
본 발명은 상기한 종래 기술의 문제점을 해결하고자 한 것으로, 생체에 적용시 자가 콜라겐 생성을 유도하고 체내 유지기간이 긴 생분해성 고분자 소재이면서도 기존 히알루론산 필러처럼 시술 직후부터 볼륨을 발현하는 생분해성 고분자 미립자 및 그 제조방법, 및 이를 포함하는 생분해성 고분자 필러를 제공하는 것을 기술적 과제로 한다.Disclosure of the Invention The present invention has been made to solve the problems of the prior art described above, and it is an object of the present invention to provide a biodegradable polymer material which induces self collagen production when applied to a living body, And a biodegradable polymer filler containing the same.
상기한 기술적 과제를 해결하고자 본 발명은, 생분해성 고분자 코어; 및 상기 코어 표면상에 코팅된 콜라겐 유도 물질;을 포함하는 생분해성 고분자 미립자를 제공한다.In order to solve the above technical problems, the present invention provides a biodegradable polymer core; And a collagen-inducing substance coated on the core surface.
본 발명의 다른 측면에 따르면, 생분해성 고분자 코어를 제공하는 단계; 및 상기 생분해성 고분자 코어의 표면에 콜라겐 유도 물질을 코팅하는 단계;를 포함하는, 생분해성 고분자 미립자의 제조방법이 제공된다.According to another aspect of the present invention, there is provided a method of manufacturing a biodegradable polymer core comprising: providing a biodegradable polymer core; And coating a collagen-inducing substance on the surface of the biodegradable polymer core.
본 발명의 또 다른 측면에 따르면, 상기 본 발명의 생분해성 고분자 미립자; 및 약제학적으로 허용 가능한 주사용 담체;를 포함하는 생분해성 고분자 필러가 제공된다.According to another aspect of the present invention, there is provided a biodegradable polymer microparticle of the present invention; And a biologically acceptable polymeric filler comprising a pharmaceutically acceptable carrier.
본 발명에 따른 생분해성 고분자 미립자를 포함하는 필러는, 생체에 적용시, 생분해성 고분자 미립자의 코어 부분은 천천히 생분해되면서 주변 조직의 자가 콜라겐 생성을 장기간 유도하여 히알루론산 필러보다 긴 유지기간을 나타내게 되며, 코어에 코팅된 콜라겐 유도 물질이 코어의 생분해가 시작되기 전에 먼저 자가 콜라겐 생성을 유도함으로써, 기존 고분자 필러에서 발생했던 시술 초기 볼륨 감소를 막아 히알루론산 필러와 같은 지속적인 볼륨을 발현시키는 역할을 한다.The filler containing biodegradable polymeric microparticles according to the present invention exhibits a longer maintenance period than the hyaluronic acid filler by inducing long-term self collagen production of surrounding tissues while slowly biodegrading the core portion of the biodegradable polymeric microparticles when applied to a living body , The core-coated collagen inducing substance induces self collagen production before biodegradation of the core starts, thereby preventing the initial volume reduction of the conventional polymer filler and thereby generating a constant volume such as a hyaluronic acid filler.
도 1은 본 발명의 일 구체예에 따른 생분해성 고분자 미립자가 갖는, 생분해성 고분자 코어의 표면에 콜라겐 유도 물질이 코팅된 구조를 개략적으로 나타낸 도면이다.BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view illustrating a structure in which a collagen-inducing substance is coated on the surface of a biodegradable polymer core of biodegradable polymeric microparticles according to one embodiment of the present invention. FIG.
이하에서 본 발명에 대하여 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 생분해성 고분자 미립자는 생분해성 고분자 코어를 포함한다.The biodegradable polymeric microparticles of the present invention include a biodegradable polymer core.
상기 생분해성 고분자 코어는 생체적합성과 생분해성을 지닌 중성 폴리머로 제조된 미립자/미립구로서, 18개월 이상의 체내 유지 기간(또는 흡수 기간)을 나타내는 것이 바람직하다. The biodegradable polymer core is a microparticle / microparticle made of a neutral polymer having biocompatibility and biodegradability and preferably exhibits a body maintenance period (or absorption period) of 18 months or longer.
상기 생분해성 고분자 코어는 생체 조직 내에서 대식 세포에 의해 탐식되지 않도록 20㎛ 이상의 직경을 가지는 것이 바람직하다. 또한, 27G 이상의 가는 주사바늘에서 60N 이하의 압력으로 원활하게 주입할 수 있고, 가급적 환자에게 통증을 유발하지 않고 주입 후 손가락 끝의 촉감으로 느낄 수 없도록, 그 직경은 100㎛ 이하인 것이 바람직하며, 40㎛ 이하인 것이 보다 바람직하다.It is preferable that the biodegradable polymer core has a diameter of 20 mu m or more so as not to be pumped by macrophages in living tissue. Further, it is preferable that the diameter is not more than 100 탆 so that the injection can smoothly be performed at a pressure of 60 N or less in a thin needle of 27 G or more and can not be felt by the touch of the fingertip after injection without causing pain to the patient as much as possible. Mu m or less.
상기 생분해성 고분자 코어는, 바람직하게는 폴리카프로락톤, 폴리락트산, 폴리글리콜산 및 이들의 공중합체로부터 선택될 수 있으며, 보다 구체적으로는 폴리-L-락트산, 폴리-D-락트산, 폴리카프로락톤 또는 이들의 공중합체일 수 있다. 이러한 생분해성 고분자의 중량평균분자량은 200,000~800,000인 것이 24개월 이상의 체내 유지 기간을 달성할 수 있어서 바람직하다.The biodegradable polymer core may preferably be selected from polycaprolactone, polylactic acid, polyglycolic acid and copolymers thereof, and more specifically polylactic acid, poly-D-lactic acid, polycaprolactone Or copolymers thereof. The biodegradable polymer preferably has a weight average molecular weight of 200,000 to 800,000 because it can achieve a sustained period of 24 months or more.
본 발명의 생분해성 고분자 미립자는, 상기한 생분해성 고분자 코어 표면상에 코팅된 콜라겐 유도 물질을 포함한다.The biodegradable polymer microparticles of the present invention include a collagen inducing substance coated on the surface of the biodegradable polymer core.
일 구체예에서, 상기 코어에 코팅되는 콜라겐 유도 물질은 칼슘 이온(Ca2 +) 공급제, 아스코르빈산, 상기 생분해성 고분자 코어보다 저분자량인 생분해성 중합체 및 이들의 조합으로부터 선택될 수 있다. 보다 구체적으로, 상기 칼슘 이온(Ca2+) 공급제는 하이드록시아파타이트, 베타-TCP(트리칼슘포스페이트), 칼슘 카보네이트 및 이들의 조합으로부터 선택될 수 있고, 상기 생분해성 고분자 코어보다 저분자량인 생분해성 중합체는 폴리글리콜산, 폴리락트산, 폴리카프로락톤, 폴리디옥사논 및 이들의 공중합체로부터 선택될 수 있다. In one embodiment, the collagen-inducing material coated on the core may be selected from a calcium ion (Ca 2 + ) feeder, ascorbic acid, a biodegradable polymer having a lower molecular weight than the biodegradable polymer core, and combinations thereof. More specifically, the calcium ion (Ca 2+ ) feeder may be selected from hydroxyapatite, beta-TCP (tricalcium phosphate), calcium carbonate, and combinations thereof, and biodegradable The polymer may be selected from polyglycolic acid, polylactic acid, polycaprolactone, polydioxanone, and copolymers thereof.
콜라겐 유도 물질로서 사용되는 생분해성 중합체의 중량평균분자량은, 예컨대, 10,000 내지 200,000 미만, 예를 들어 10,000 내지 190,000의 범위 내에서 상기 코어로서 사용된 생분해성 고분자보다 저분자량이며, 따라서 그 보다 빠른 생분해 속도를 나타낸다.The weight average molecular weight of the biodegradable polymer used as the collagen inducing material is lower than that of the biodegradable polymer used as the core within the range of, for example, 10,000 to less than 200,000, for example, 10,000 to 190,000, It represents speed.
코어상에 코팅된 콜라겐 유도 물질의 양에는 특별한 제한이 없으며, 예컨대, 코어 100중량부를 기준으로, 1 내지 10 중량부의 콜라겐 유도 물질이 코팅될 수 있으나, 이에 한정되지 않는다.There is no particular limitation on the amount of the collagen-inducing substance coated on the core. For example, 1 to 10 parts by weight of the collagen-inducing substance may be coated on the basis of 100 parts by weight of the core, but is not limited thereto.
본 발명의 다른 측면에 따르면, 생분해성 고분자 코어를 제공하는 단계; 및 상기 생분해성 고분자 코어의 표면에 콜라겐 유도 물질을 코팅하는 단계;를 포함하는, 생분해성 고분자 미립자의 제조방법이 제공된다.According to another aspect of the present invention, there is provided a method of manufacturing a biodegradable polymer core comprising: providing a biodegradable polymer core; And coating a collagen-inducing substance on the surface of the biodegradable polymer core.
생분해성 고분자 코어를 제조하는 방법으로는 이 기술 분야에서 일반적으로 사용되는 용매증발법, 침전법, 냉각분쇄법 또는 기타 고분자 미립자/미립구 제조방법을 사용할 수 있으며, 그러한 방법에 의해 본 발명이 제한되지는 않는다.As a method for producing the biodegradable polymer core, a solvent evaporation method, a precipitation method, a cooling milling method, or other polymer microparticle / microparticle production method generally used in this technical field can be used. .
콜라겐 유도 물질을 코어 표면에 코팅하는 방법으로는 이 기술 분야에서 일반적으로 사용되는 솔리드 레이어링(solid layering), 용액법, 침전법, 하부스프레이코팅법(bottom spray coating) 등이 모두 사용될 수 있으며, 그러한 방법에 의해 본 발명이 제한되지는 않는다.As a method of coating the collagen-inducing material on the core surface, solid layering, solution method, precipitation method, bottom spray coating, etc. commonly used in this technical field can be used. The present invention is not limited by the method.
생분해성 고분자 코어는 체내에서 장기간 동안 유지되지만 그 때문에 생분해가 시작되는 시점이 늦다. 따라서, 담체(예컨대, 카르복시메틸셀룰로오스(CMC) 수용액)와 함께 체내에 주입된 후 단 며칠 만에 흡수되기 때문에, 피부의 볼륨이 감소할 때까지 콜라겐 합성을 유도해 낼 수 없다. 이것이 바로 기존의 고분자 필러가 지닌 가장 치명적인 단점인 시술 초기 볼륨의 급격한 감소를 가져오는 원인이다.Biodegradable polymer cores are maintained in the body for a long period of time, but the time for biodegradation to start is slow. Therefore, collagen synthesis can not be induced until the volume of the skin is reduced, since it is absorbed in only a few days after it is injected into the body together with a carrier (for example, an aqueous solution of carboxymethyl cellulose (CMC)). This is the cause of the drastic decrease in the initial volume of the procedure, which is the most fatal disadvantage of the existing polymer filler.
반면, 본 발명에서는 생분해성 고분자 코어보다 생분해가 빨라 콜라겐 생성을 조기에 유도할 수 있는 물질을 코어 표면에 코팅함으로써, 시술 초기의 볼륨 감소는 코팅 물질이 콜라겐을 유도하여 막고, 그 이후의 장기 볼륨은 코어의 생분해 작용으로 유지하여 시술 초기 볼륨 감소가 없으면서도 히알루론산 필러보다 유지기간이 긴 이상적인 필러를 제조할 수 있다.On the other hand, in the present invention, by coating a material capable of inducing collagen production early on biodegradation faster than biodegradable polymer cores on the surface of the core, volume reduction at the initial stage of treatment prevents the coating material from inducing collagen, It is possible to produce an ideal filler having a longer holding period than the hyaluronic acid filler without the volume reduction at the initial stage of the treatment by maintaining the biodegradation action of the core.
따라서, 본 발명의 또 다른 측면에 따르면, 상기 본 발명의 생분해성 고분자 미립자; 및 약제학적으로 허용 가능한 주사용 담체;를 포함하는 생분해성 고분자 필러가 제공된다.Therefore, according to another aspect of the present invention, there is provided a biodegradable polymer microparticle of the present invention; And a biologically acceptable polymeric filler comprising a pharmaceutically acceptable carrier.
상기 약제학적으로 허용 가능한 주사용 담체로는, 예컨대, 생리식염수, 인산 버퍼 등의 주사용 수용액을 사용할 수 있다. 또한, 이러한 담체는 필요에 따라 카르복시메틸셀룰로오스(CMC), 하이드록시프로필메틸셀룰로오스(HPMC) 등의 셀룰로오스 유도체, 히알루론산 등의 용질, 글리세린 등의 윤활제를 하나 이상 더 포함할 수 있으나, 이에 한정되지는 않는다.As the above pharmaceutically acceptable carrier for injectable use, for example, a physiological saline solution, a phosphate buffer and the like can be used. The carrier may further include one or more lubricants such as cellulose derivatives such as carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC), solutes such as hyaluronic acid, and glycerin, but are not limited thereto .
일 구체예에서, 본 발명의 생분해성 고분자 필러에 포함되는 각 성분의 함량은, 필러 제형 총 100중량%를 기준으로, 상기 생분해성 고분자 미립자 20~50중량%, 수용액 10~69중량%, 용질 1~10중량%, 분산제 10~30중량%일 수 있으나, 이에 한정되지는 않는다.In one embodiment, the content of each component contained in the biodegradable polymeric filler of the present invention is 20 to 50% by weight of the biodegradable polymeric microparticles, 10 to 69% by weight of the aqueous solution, 1 to 10% by weight, and the dispersing agent may be 10 to 30% by weight.
콜라겐 유도 물질이 코팅된 생분해성 고분자 미립자를 담체에 현탁함으로써 본 발명의 필러 제형이 얻어질 수 있으며, 이 필러 제형은 주사바늘이 달려있는 즉시 사용가능한 멸균 주사기 또는 멸균 바이알에 넣어 제공할 수 있다.The pellet formulation of the present invention can be obtained by suspending biodegradable polymeric microparticles coated with collagen inducing material on a carrier, which can be provided in a sterile syringe or a sterilizing vial ready for use with an injection needle.
본발명의 생분해성 고분자 필러는 전처리가 필요 없어 사용편의성이 높고, 주입 후 정해진 시간에 걸쳐 100% 생분해되기 때문에 생체 조직 내에 이물질을 남기지 않아 안전하며 동물 유래 물질을 전혀 포함하지 않기 때문에 알러지를 일으키지 않는다. 또한, 시술 초기 볼륨 감소가 없으면서도 히알루론산 필러보다 유지기간이 길어, 특히 안면용 필러로서 매우 적합하다.The biodegradable polymeric filler of the present invention does not require any pretreatment and is highly convenient to use. Since it is 100% biodegradable over a predetermined period of time after injection, it is safe because it does not leave any foreign material in the living tissue and does not contain any animal- . In addition, it is more suitable as a facial filler, because it has a longer maintenance period than a hyaluronic acid filler even when there is no volume reduction at the initial stage of the procedure.
이하의 실시예에 의거하여 본 발명을 보다 상세히 설명하나, 본 발명이 이에 한정되는 것은 아니다.The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.
[실시예][Example]
실시예 1Example 1
12g의 폴리락트산(중량평균분자량: 410,000)을 200㎖의 유기용매(디클로로메탄)에 용해시키고, 이 용액을, 10g의 폴리비닐아세테이트를 포함하는 500㎖의 물에 조금씩 주입하면서 평균입경이 30㎛인 미립자가 형성될 때까지 지속적으로 고속 교반하였다. 형성된 미립자를 침강, 여과 및 건조하여 회수하였다. 이어서, 상기 미립자에 콜라겐 유도 물질로서 하이드록시아파타이트를 솔리드 레이어링(solid layering)으로 코팅한 후 생리식염 주사용수와 카르복시메틸셀룰로오스(2wt.%)를 포함하는 담체에 넣고, 완만하게 교반한 후에 분배하였다.12 g of polylactic acid (weight average molecular weight: 410,000) was dissolved in 200 ml of an organic solvent (dichloromethane), and this solution was gradually injected into 500 ml of water containing 10 g of polyvinyl acetate, And stirred continuously at high speed until phosphorus particles were formed. The formed microparticles were collected by sedimentation, filtration and drying. Then, hydroxyapatite as a collagen-inducing substance was coated on the microparticles by solid layering, and the mixture was put into a carrier containing physiological saline solution and carboxymethylcellulose (2 wt.%), Gently stirred and dispensed .
실시예 2Example 2
500g의 폴리카프로락톤(중량평균분자량: 240,000)을 냉각분쇄한 후 분별하여 최종 입경이 20~40㎛이면서 평균입경이 30㎛인 미립자를 얻었다. 이어서, 상기 미립자에 콜라겐 유도 물질로서 폴리글리콜산-폴리락트산 공중합체(PGLA)(중량평균분자량: 130,000)를 용액법으로 코팅한 후 인산 버퍼와 카르복시메틸셀룰로오스(2wt.%) 및 글리세린(20wt.%)을 포함하는 담체에 넣고, 완만하게 교반한 후에 분배하였다.500 g of polycaprolactone (weight-average molecular weight: 240,000) was cooled and pulverized and then fractionated to obtain fine particles having a final particle diameter of 20 to 40 占 퐉 and an average particle diameter of 30 占 퐉. Then, the microparticles were coated with a solution of polyglycolic acid-polylactic acid copolymer (PGLA) (weight average molecular weight: 130,000) as a collagen inducing substance by a solution method, and then the cells were treated with phosphate buffer, carboxymethylcellulose (2 wt.%) And glycerin (20 wt. %), And the mixture was gently stirred and then dispensed.
비교예 1Comparative Example 1
코팅 공정만을 생략하고, 실시예 1과 동일한 과정을 수행하였다.The same procedure as in Example 1 was performed, omitting only the coating process.
비교예 2Comparative Example 2
코팅 공정만을 생략하고, 실시예 2와 동일한 과정을 수행하였다.The same procedure as in Example 2 was performed, omitting only the coating process.
실시예 1, 2, 비교예 1, 2에서 얻어진 필러 제형에 대하여, 헤어리스 마우스를 이용하여 동물효능시험을 진행하였으며, 그 결과를 하기 표 1에 나타내었다.An animal efficacy test was carried out using the hairless mouse on the filler formulations obtained in Examples 1 and 2 and Comparative Examples 1 and 2, and the results are shown in Table 1 below.
표 1로부터 알 수 있듯이, 콜라겐 유도 물질로 코팅된 고분자 미립자를 포함한 실시예의 필러 제형의 경우 시술 초기 볼륨 감소가 현저히 개선되었다.As can be seen from Table 1, in the case of the filler formulations of the Examples including the polymer fine particles coated with the collagen inducer, the initial volume reduction of the procedure was remarkably improved.
Claims (10)
약제학적으로 허용 가능한 주사용 담체;를 포함하며,
상기 코어에 코팅되는 콜라겐 유도 물질이 상기 생분해성 고분자 코어보다 저분자량인 생분해성 중합체인,
생분해성 고분자 필러.Biodegradable polymeric microparticles comprising a biodegradable polymer core and a collagen inducing material coated on the core surface; And
A pharmaceutically acceptable carrier; and a pharmaceutically acceptable carrier,
Wherein the collagen-inducing material coated on the core is a biodegradable polymer having a lower molecular weight than the biodegradable polymer core,
Biodegradable polymeric filler.
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| KR102266385B1 (en) * | 2021-01-22 | 2021-06-21 | 주식회사 울트라브이 | Biogradable polymer fine particle for filler, preparing method thereof, freeze-dried product for filler including the same, and injection for filler including the same |
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