KR101852127B1 - Manufacture method for combination of Poly L lactic acid dermal filler and hyaluronic acid dermal filler - Google Patents

Manufacture method for combination of Poly L lactic acid dermal filler and hyaluronic acid dermal filler Download PDF

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KR101852127B1
KR101852127B1 KR1020160044271A KR20160044271A KR101852127B1 KR 101852127 B1 KR101852127 B1 KR 101852127B1 KR 1020160044271 A KR1020160044271 A KR 1020160044271A KR 20160044271 A KR20160044271 A KR 20160044271A KR 101852127 B1 KR101852127 B1 KR 101852127B1
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김창식
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Abstract

본 발명은 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법을 제공하기 위한 것으로, PLLA에 CMC와 마니톨을 섞은 후 동결 건조시키고, 일정한 크기로 분쇄하여 바이얼에 담고, 감마레이 멸균을 실시하여 바이얼에 담긴 PLLA 혼합물을 제조하는 PLLA 혼합물 제조단계와; HA를 BDDE 가교제와 섞은 후 젤화시키고, 인산완충액으로 세척한 다음, 균일한 입자의 가교 HA를 얻은 후 바이얼에 충진 후 고압멸균시켜 바이얼에 담긴 HA 혼합물을 제조하는 HA 혼합물 제조단계와; HA 혼합물을 증류수에 믹스 후 PLLA 혼합물에 주입하고 혼합하여 주사기로 뽑아 시술할 수 있도록 하는 혼합 단계;를 포함하여 수행함으로서, PLLA와 HA의 결합체를 제조하기 위하여 PLLA를 동결건조하고 BDDE를 이용하여 HA를 가교하며, 가교한 HA를 PLLA 바이얼에 주입하여 믹스한 후 주사기로 뽑아 시술할 수 있게 된다.The present invention provides a method for producing a polylactic acid filler and a hyaluronic acid filler conjugate, which comprises mixing PLLA with CMC and mannitol, freeze-drying, pulverizing the mixture into a predetermined size, and vial- A PLLA mixture preparation step of preparing a vial-containing PLLA mixture; A HA mixture preparation step of mixing the HA with the BDDE cross-linking agent, gelling the HA agent, washing with a phosphate buffer, obtaining homogeneous cross-linked HA, filling the vial, and autoclaving to produce a HA mixture in the vial; HA mixture was mixed with distilled water, and then injected into a PLLA mixture, and mixed and injected into a syringe. Thus, PLLA was lyophilized to prepare a conjugate of PLLA and HA, and HA , Cross-linked HA is injected into PLLA vial, mixed, and then pulled out with a syringe.

Description

폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법{Manufacture method for combination of Poly L lactic acid dermal filler and hyaluronic acid dermal filler}[0001] The present invention relates to a polylactic acid filler and a hyaluronic acid filler,

본 발명은 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법에 관한 것으로, 특히 폴리엘락틱산(Poly L lactic acid, 이하 "PLLA"라 한다) 필러와 히알루론산(hyaluronic acid, 이하 "HA"라 한다) 필러의 결합체를 제조하기 위하여 PLLA를 동결건조하고 BDDE(ButaneDiol Diglycidyl Ether, 부탄디올 디글리시딜 에테르)를 이용하여 HA를 가교하며, 가교한 HA를 PLLA 바이얼에 주입하여 믹스한 후 주사기로 뽑아 시술할 수 있도록 하기에 적당하도록 한 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법에 관한 것이다.The present invention relates to a method for producing a polylactic acid filler and a hyaluronic acid filler conjugate, and more particularly to a polylactic acid filler and hyaluronic acid (HA) ), HA was cross-linked using BDDE (butane diol diglycidyl ether, butanediol diglycidyl ether), and the cross-linked HA was injected into PLLA vial, mixed and pulled out with a syringe The present invention relates to a polylactic acid filler and a method for producing a hyaluronic acid filler conjugate, which is suitable to be made operable.

일반적으로 폴리엘락틱산(Poly L lactic acid, "PLLA") 필러는 미립구의 지지체로서 생체 적합성 및 생분해성 특성을 갖고 있는 고분자 합성물질이다. 또한 히알루론산(hyaluronic acid, HA)은 동물 등의 피부에 많이 존재하는 생체 합성 천연 물질로서, 히알루론산(HA) 필러는 수술 없이 안면 볼륨을 증가시키는데 사용되는 물질이다.Generally, polylactic acid (PLLA) filler is a polymer synthesis material having biocompatibility and biodegradability as a microparticle support. In addition, hyaluronic acid (HA) is a biosynthetic natural substance that exists in a lot of skin such as animals. Hyaluronic acid (HA) filler is a material used for increasing the facial volume without surgery.

도 1은 종래 PLLA의 제조 및 사용방법을 보인 흐름도이다.FIG. 1 is a flowchart showing a method of manufacturing and using a conventional PLLA.

이에 도시된 바와 같이, 건조된 파우더(Powder) 형태의 PLLA를 CMC(carboxy methy cellulose, 카르복시메틸셀룰로스)와 마니톨(Mannitol)과 섞은 상태로 동결 건조시킨다(ST1). 그리고 동결 건조된 PLLA를 멸균 증류수에 섞어서(ST2), 현탁액으로 제조한다(ST3). 그런 다음 제조된 현탁액을 체내에 주사할 수 있도록 한다(ST4).As shown in the figure, PLLA in powder form is freeze-dried (ST1) in a state mixed with carboxy methyl cellulose (CMC) and mannitol (CMC). The lyophilized PLLA is mixed with sterile distilled water (ST2) to prepare a suspension (ST3). The prepared suspension is then injected into the body (ST4).

그러면 3~6개월이 경과한 후에 체내에 콜라겐이 생성되어 볼륨이 증대되는 효과가 나타나게 된다(ST5).Then, after 3 to 6 months, collagen is produced in the body and the volume is increased (ST5).

그러나 이러한 종래 기술은 여기서 몇 가지 문제점이 발생하게 된다. 즉, 주입된 PLLA 현탁액 중에 증류수 성분과 CMC 성분은 수일 내에 체내에 흡수되어 버린다. 이렇게 증류수 성분과 CMC 성분이 흡수되어 사라져 버리기 때문에, PLLA 현탁액을 체내에 주사한 직후에 생겼던 볼륨감이 즉시 사라지게 된다. 따라서 체내 주사 후 몇일이 경과하면 볼륨 증대 효과를 보이지 못하게 된다. 그리고 수개월(3~6개월)이 지난 후에야 볼륨이 증대된 효과가 서서히 나타나게 된다.However, such conventional techniques cause some problems here. That is, the distilled water component and the CMC component in the injected PLLA suspension are absorbed into the body within a few days. Since the distilled water component and the CMC component are absorbed and disappeared, the volume feeling immediately after injecting the PLLA suspension into the body disappears immediately. Therefore, the volume increase effect will not be shown after a few days after injection. And after a few months (3 to 6 months), the effect of increasing volume is slowly appearing.

이처럼 체내 주입후 콜라겐이 생성될 때까지의 수개월이 경과하여야만 하는데, 이러한 수개월의 시간은 피시술자에게 불만을 야기시키는 원인이 되었다.As such, several months must elapse until the collagen is formed after injection into the body, and these several months cause complaints to the recipient.

그리고 위의 단점을 보완하기 위해 PLLA 입자가 골고루 체내에서 분포될 수 있도록 하고, PLLA 주입 후 콜라겐이 생성되어 볼륨을 만들 때까지 3-6개월간 초기 볼륨을 형성하기 위해서는 다른 종류의 필러(filler) 인체 조직수복용 생체재료를 같이 사용해야만 하는 불편함도 있었다.In order to compensate for the disadvantages described above, PLLA particles are uniformly distributed in the body, and collagen is formed after PLLA injection to form an initial volume for 3-6 months until the volume is formed. There was an inconvenience that biomaterials for tissue repair should be used together.

또한 종래의 PLLA 필러는 결절(nodule), 육아종(granuloma)이 생성되는 단점이 있었다.In addition, conventional PLLA fillers have disadvantages such as nodule and granuloma.

또한 증류수와 희석해서 PLLA를 주사하게 되는데, 이때 증류수가 현탁액을 만들 경우 현탁액의 농도가 낮아지게 된다. 이 때문에 균일한 현탁액을 만들기 위해서는 장시간의 시간이 필요하게 되는 문제점도 있었다.In addition, diluted PLLA is injected with distilled water. When the distilled water is made into a suspension, the concentration of the suspension is lowered. For this reason, a long time is required to form a uniform suspension.

또한 특허문헌으로는 대한민국 공개특허 제2002-0022160호의 "고분자량 폴리엘락틱산의 제조방법"이 개시된 바 있다. 이는 고분자량 폴리L-락틱산의 합성을 위하여 락틱산의 환상이량체인 락타이드를 거치지 않고 락틱산으로부터 무용제하에서의 직접탈수축합중합에 의하여 고분자량의 폴리L-락틱산을 제조하기 위하여 L-락틱산의 올리고머(Oligo(L-lactic acid) )를 무촉매상에서 탈수축합 반응시킨 후 촉매로써 일정비율의 Sn화합물과 proton산을 첨가 감압조건하 직접탈수축합중합에 의하여 저분자량의 폴리L-락틱산을 합성하고 이어서 결정화도를 높이기 위해 예열과정을 거친후 고상중합을 시행 하는 것을 특징으로 한다.As a patent document, "a process for producing high molecular weight polylactic acid" of Korean Patent Publication No. 2002-0022160 has been disclosed. In order to prepare high molecular weight poly L-lactic acid by direct dehydration condensation polymerization from lactic acid without using lactide, which is a cyclic dimer of lactic acid, for the synthesis of high molecular weight poly L-lactic acid, L- After dehydration condensation of oligo (L-lactic acid) of tic acid, a certain amount of Sn compound and proton acid was added as a catalyst, and dehydration condensation polymerization was carried out under reduced pressure to obtain poly (L-lactic acid And the solid phase polymerization is carried out after preheating to increase the degree of crystallization.

그러나 이러한 선행기술문헌은 폴리엘락틱산 필러(PLLA)의 제조 및 사용에 따른 종래 문제점을 해결하지 못한 한계가 있었다.However, these prior art documents have limitations in solving the conventional problems associated with the manufacture and use of polylactic acid filler (PLLA).

KRKR 10-2002-002216010-2002-0022160 AA

이에 본 발명은 상기와 같은 종래의 제반 문제점을 해결하기 위해 제안된 것으로, 본 발명의 목적은 폴리엘락틱산(PLLA) 필러와 히알루론산(HA) 필러의 결합체를 제조하기 위하여 PLLA를 동결건조하고 BDDE를 이용하여 HA를 가교하며, 가교한 HA를 PLLA 바이얼에 주입하여 믹스한 후 주사기로 뽑아 시술할 수 있도록 할 수 있는 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법을 제공하는데 있다.DISCLOSURE Technical Problem Accordingly, the present invention has been made to solve the above-mentioned problems of the prior art, and an object of the present invention is to provide a method of preparing a conjugate of a polylactic acid (PLLA) filler and a hyaluronic acid (HA) filler by freeze- And a method for preparing a polylactic acid filler and a hyaluronic acid filler conjugate, which can cross-link the HA using the cross-linked HA, and then inject the cross-linked HA into a PLLA vial, mix it, and pull it out with a syringe.

도 2는 본 발명의 일 실시예에 의한 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법을 보인 흐름도이다.FIG. 2 is a flow chart showing a method for producing a polylactic acid filler and a hyaluronic acid filler conjugate according to an embodiment of the present invention.

이에 도시된 바와 같이, PLLA(폴리엘락틱산)에 CMC(카르복시메틸셀룰로스)와 마니톨(Mannitol)을 섞은 후 동결 건조시키고, 일정한 크기로 분쇄하여 바이얼(Vial)에 담고, 감마레이 멸균을 실시하여 바이얼에 담긴 PLLA 혼합물을 제조하는 PLLA 혼합물 제조단계(ST11 ~ ST13)와; HA(히알루론산)를 BDDE(부탄디올 디글리시딜 에테르) 가교제와 섞은 후 젤화시키고, 인산완충액으로 세척한 다음, 균일한 입자의 가교 HA를 얻은 후 바이얼에 충진 후 고압멸균시켜 바이얼에 담긴 HA 혼합물을 제조하는 HA 혼합물 제조단계(ST21 ~ ST23)와; 상기 HA 제조단계의 HA 혼합물을 증류수에 믹스 후 상기 PLLA 혼합물 제조단계의 PLLA 혼합물에 주입하고 혼합하여 주사기로 뽑아 시술할 수 있도록 하는 혼합 단계(ST31, ST32);를 포함하여 수행하는 것을 특징으로 한다.As shown in the figure, PLLA (polylactic acid) was mixed with CMC (carboxymethyl cellulose) and mannitol, followed by lyophilization, pulverization into a uniform size, vials, and gamma ray sterilization A PLLA mixture preparation step (ST11 to ST13) for preparing a vial-containing PLLA mixture; HA (hyaluronic acid) is mixed with BDDE (butanediol diglycidyl ether) cross-linking agent and gelated. After washing with phosphate buffer, homogeneous cross-linked HA is obtained, filled in vials and autoclaved. A HA mixture preparation step (ST21 to ST23) for producing a HA mixture; (ST31, ST32) in which the HA mixture in the HA preparation step is mixed with distilled water, injected into the PLLA mixture of the PLLA mixture preparation step, mixed and injected into a syringe, .

상기 PLLA 혼합물 제조단계는, 동결건조의 초기 동결온도는 영하 60~100도 사이가 되도록 하고, 추후 건조온도는 15~25도에서 5일~10일 동안 건조되도록 하고, 분쇄한 입자의 크기는 30um~100um(마이크로미터)의 범위 이내가 되도록 하는 것을 특징으로 한다.In the PLLA mixture preparation step, the initial freezing temperature of the freeze-drying is set to be in the range of minus 60 to 100 degrees, and the drying temperature is 15 to 25 degrees for 5 days to 10 days. The size of the pulverized particles is 30um To 100 m (micrometers).

상기 HA 혼합물 제조단계는, 인산완충액은 HA 100gram 당 30~80리터를 사용하도록 하고, 80~120메쉬(Mesh)의 크기로 통과시켜 균일한 입자의 가교 HA를 얻는 것을 특징으로 한다.The HA preparation step is characterized in that 30 to 80 liters of phosphate buffer solution is used per 100 grams of HA, and is passed through a size of 80 to 120 meshes to obtain homogeneous HA of crosslinked particles.

상기 혼합 단계는, 페이스용의 HA를 제조할 경우 HA 10cc 당 증류수 15~25cc를 사용하고, 바디용의 HA를 제조할 경우 HA 10cc 당 증류수 25~35cc를 사용하는 것을 특징으로 한다.The mixing step is characterized by using 15 to 25 cc of distilled water per 10 cc of HA when preparing HA for the face and 25 to 35 cc of distilled water per 10 cc of HA when preparing HA for a body.

상기 혼합 단계는, HA 혼합물을 PLLA 혼합물에 주입한 후 3~8분간 흔들어 주는 단계를 포함하여 수행하는 것을 특징으로 한다.The mixing step is performed by injecting the HA mixture into the PLLA mixture and shaking the mixture for 3 to 8 minutes.

본 발명에 의한 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법은 폴리엘락틱산(PLLA) 필러와 히알루론산(HA) 필러의 결합체를 제조하기 위하여 PLLA를 동결건조하고 BDDE를 이용하여 HA를 가교하며, 가교한 HA를 PLLA 바이얼에 주입하여 믹스한 후 주사기로 뽑아 시술할 수 있도록 할 수 있는 효과가 있게 된다.The polylactic acid filler and the hyaluronic acid filler conjugate according to the present invention are prepared by lyophilizing PLLA to prepare a conjugate of a polylactic acid (PLLA) filler and a hyaluronic acid (HA) filler, crosslinking the HA using BDDE , Cross-linked HA can be injected into PLLA vials, mixed and then injected into a syringe.

또한 본 발명은 PLLA가 주사 후 즉각적인 효과를 보이기 위해 HA를 믹스한 후 주사하면 초기 볼륨은 HA가 6개월에서 1년 정도 담당하고, 후반의 체내 볼륨은 PLLA가 콜라겐을 생성함으로 해결한 효과가 있다.In addition, the present invention has an effect that PLLA is injected after mixing with HA to show an immediate effect, and the initial volume is for HA for 6 months to 1 year, and the volume of the latter volume is solved by PLLA producing collagen .

또한 HA와 PLLA를 섞음으로서 PLLA 입자들이 점도가 있는 HA 안에서 현탁액 상태로 골고루 분포하기 때문에 PLLA가 한 곳에 뭉치지 않아 육아종 형성을 덜하게 되는 효과도 있다.In addition, by mixing HA and PLLA, PLLA particles are uniformly dispersed in a suspension state in a viscous HA, so that PLLA does not aggregate in one place, thereby reducing granuloma formation.

도 1은 종래 PLLA의 제조 및 사용방법을 보인 흐름도이다.
도 2는 본 발명의 일 실시예에 의한 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법을 보인 흐름도이다.FIG. 1 is a flowchart showing a method of manufacturing and using a conventional PLLA.
FIG. 2 is a flow chart showing a method for producing a polylactic acid filler and a hyaluronic acid filler conjugate according to an embodiment of the present invention.

이와 같이 구성된 본 발명에 의한 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법의 바람직한 실시예를 첨부한 도면에 의거하여 상세히 설명하면 다음과 같다. 하기에서 본 발명을 설명함에 있어 관련된 공지 기능 또는 구성에 대한 구체적인 설명이 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략할 것이다. 그리고 후술되는 용어들은 본 발명에서의 기능을 고려하여 정의된 용어들로서, 이는 사용자, 운용자의 의도 또는 판례 등에 따라 달라질 수 있으며, 이에 따라 각 용어의 의미는 본 명세서 전반에 걸친 내용을 토대로 해석되어야 할 것이다.Preferred embodiments of the polylactic acid filler and hyaluronic acid filler-bonded body according to the present invention having the above-described structure will be described in detail with reference to the accompanying drawings. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted when it may make the subject matter of the present invention rather unclear. It is to be understood that the following terms are defined in consideration of the functions of the present invention, and may be changed according to the intention of the user, the operator, or the precedent, and the meaning of each term should be interpreted based on the contents will be.

먼저 본 발명은 폴리엘락틱산(PLLA) 필러와 히알루론산(HA) 필러의 결합체를 제조하기 위하여 PLLA를 동결건조하고 BDDE를 이용하여 HA를 가교하며, 가교한 HA를 PLLA 바이얼에 주입하여 믹스한 후 주사기로 뽑아 시술할 수 있도록 하고자 한 것이다.The present invention relates to a method for preparing a conjugate of a polylactic acid (PLLA) filler and a hyaluronic acid (HA) filler by lyophilizing PLLA, crosslinking HA using BDDE, injecting crosslinked HA into PLLA vial So that it can be removed by a syringe.

도 2는 본 발명의 일 실시예에 의한 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법을 보인 흐름도이다.FIG. 2 is a flow chart showing a method for producing a polylactic acid filler and a hyaluronic acid filler conjugate according to an embodiment of the present invention.

PLLA 혼합물 제조단계(ST11 ~ ST13)에서는 먼저 분자량 15만 Kda(킬로돌턴, Kilo dalton) 정도의 PLLA(폴리엘락틱산)를 준비한다. 이러한 PLLA에 CMC(카르복시메틸셀룰로스)와 마니톨(Mannitol)을 섞은 후 동결 건조시킨다. 이 때 동결건조의 초기 동결온도는 영하 60~100도 사이가 되도록 하고, 추후 건조온도는 15~25도에서 5일~10일 동안 건조되도록 한다.In the PLLA mixture preparation steps (ST11 to ST13), PLLA (polylactic acid) having a molecular weight of about 150,000 Kda (kilo-dalton, Kilo dalton) is first prepared. The PLLA is mixed with CMC (carboxymethyl cellulose) and mannitol, followed by lyophilization. At this time, the initial freezing temperature of the freeze-drying is between 60 and 100 degrees Celsius, and the drying temperature is 15 to 25 degrees Celsius for 5 days to 10 days.

이처럼 동결건조 후 일정한 크기로 분쇄하여 바이얼(Vial)에 담는다. 이때 분쇄한 입자의 크기는 30um~100um(마이크로미터)의 범위 이내(적절하게는 50um)가 되도록 한다. 또한 분쇄는 일반적인 오버헤드 스티어러를 이용할 수 있다.After lyophilization, it is pulverized to a certain size and placed in a vial. At this time, the size of the pulverized particles should be within the range of 30um to 100um (micrometer) (suitably 50um). Also, grinding can utilize a common overhead steerer.

그리고 감마레이 멸균을 실시하여 바이얼에 담긴 PLLA 혼합물을 제조한다.And gamma ray sterilization is performed to prepare a vial-loaded PLLA mixture.

한편 HA 혼합물 제조단계(ST21 ~ ST23)에서는 먼저 분자량 200만 Kda 정도의 HA(히알루론산)를 준비한다. 이렇게 준비한 HA를 일정한 비율로 BDDE(부탄디올 디글리시딜 에테르) 가교제와 섞은 후 젤화시킨다. 젤화된 HA는 인산완충액으로 세척한다. 인산완충액은 HA 100gram 당 30~80리터(적절하게는 50리터)를 사용하도록 한다.On the other hand, HA (hyaluronic acid) having a molecular weight of about 2,000,000 Kda is first prepared in the HA preparation step (ST21 to ST23). The prepared HA is mixed with BDDE (butanediol diglycidyl ether) crosslinking agent at a certain ratio, and then gelated. The gelled HA is washed with phosphate buffer. Phosphate buffers should be used at 30 to 80 liters (appropriately 50 liters) per 100 grams of HA.

그리고 세척한 HA를 일정한 크기의 메쉬를 통과시켜 균일한 입자의 가교 HA를 얻는다. 이때 80~120메쉬(Mesh)의 크기로 통과시켜 균일한 입자의 가교 HA를 얻을 수 있다. 최적의 메쉬 구멍의 크기는 100메쉬를 사용할 수 있다.Then, the washed HA is passed through a mesh of a certain size to obtain uniform HA of crosslinked particles. At this time, the cross-linked HA of a uniform particle can be obtained by passing through a size of 80 ~ 120 mesh (mesh). The optimal mesh hole size is 100 mesh.

그런 다음 가교 HA를 바이얼에 충진 후 고압멸균시켜 바이얼에 담긴 HA 혼합물을 제조한다.The HA is then filled in vials and autoclaved to produce a vial-filled HA mixture.

또한 혼합 단계에서는 HA 혼합물 제조단계의 HA를 증류수에 믹스 후 상기 PLLA 혼합물 제조단계의 PLLA 혼합물에 주입하고 혼합하여 주사기로 뽑아 시술할 수 있도록 한다. 이때 페이스용의 HA를 제조할 경우 HA 10cc 당 증류수 15~25cc(적절하게는 20cc)를 사용하고, 바디용의 HA를 제조할 경우 HA 10cc 당 증류수 25~35cc(적절하게는 30cc)를 사용한다. 또한 HA를 PLLA 바이얼에 주입한 후 3~8분간(적절하게는 5분간) 흔들어 준 후 사용할 수 있도록 한다.In the mixing step, the HA of the HA preparation step is mixed with distilled water, and then the mixture is injected into the PLLA mixture of the PLLA preparation step, and the mixture is injected with a syringe. At this time, 15 to 25 cc (suitably 20 cc) of distilled water per 10 cc of HA is used when producing HA for face, and 25 to 35 cc (suitably 30 cc) of distilled water per 10 cc of HA is used when preparing HA for body . In addition, HA is injected into the PLLA vial and allowed to shake for 3 to 8 minutes (suitably 5 minutes) before use.

이와 같이 본 발명은 종래의 PLLA 필러 제품(예, 스컬트라 등의 제품)의 단점인 주입시 초기볼륨 형성까지의 시간을 6~8주 이상을 단축시키고, 기존 PLLA 필러의 다른 단점인 육아종 형성을 최소하하기 위해서 가교 히알루론산을 묶음 상품으로 개발하였다.As described above, the present invention can shorten the time for forming the initial volume during injection, which is a disadvantage of conventional PLLA filler products (e.g., Sculptor), to 6 to 8 weeks or more, In order to minimize it, we developed crosslinked hyaluronic acid as a bundled product.

이처럼 본 발명은 폴리엘락틱산(PLLA) 필러와 히알루론산(HA) 필러의 결합체를 제조하기 위하여 PLLA를 동결건조하고 BDDE를 이용하여 HA를 가교하며, 가교한 HA를 PLLA 바이얼에 주입하여 믹스한 후 주사기로 뽑아 시술할 수 있게 된다.As such, the present invention relates to a method for preparing a conjugate of a polylactic acid (PLLA) filler and a hyaluronic acid (HA) filler by lyophilizing PLLA, crosslinking HA using BDDE, injecting crosslinked HA into PLLA vial And can be removed by a syringe.

이상에서 실시예를 들어 본 발명을 더욱 상세하게 설명하였으나, 본 발명은 반드시 이러한 실시예로 국한되는 것은 아니고, 본 발명의 기술사상을 벗어나지 않는 범위 내에서 다양하게 변형실시될 수 있다. 따라서 본 발명에 개시된 실시예들은 본 발명의 기술적 사상을 한정하기 위한 것이 아니라 설명하기 위한 것이고, 이러한 실시예에 의하여 본 발명의 기술적 사상의 범위가 한정되는 것은 아니다. 본 발명의 보호범위는 청구범위에 의하여 해석되어야 하며, 그와 동등한 범위 내에 있는 모든 기술적 사상은 본 발명의 권리범위에 포함되는 것으로 해석되어야 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not to be limited to the details thereof, and various changes and modifications may be made without departing from the spirit and scope of the invention. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but are intended to illustrate and not limit the scope of the technical spirit of the present invention. The scope of protection of the present invention should be construed according to the claims, and all technical ideas which are within the scope of the same should be interpreted as being included in the scope of the present invention.

Claims (5)

PLLA(폴리엘락틱산)에 CMC(카르복시메틸셀룰로스)와 마니톨을 섞은 후 동결 건조시키고, 일정한 크기로 분쇄하여 바이얼에 담고, 감마레이 멸균을 실시하여 바이얼에 담긴 PLLA 혼합물을 제조하는 PLLA 혼합물 제조단계와;
HA(히알루론산)를 BDDE(부탄디올 디글리시딜 에테르) 가교제와 섞은 후 젤화시키고, 인산완충액으로 세척한 다음, 균일한 입자의 가교 HA를 얻은 후 바이얼에 충진 후 고압멸균시켜 바이얼에 담긴 HA 혼합물을 제조하는 HA 혼합물 제조단계와;
상기 HA 혼합물 제조단계의 HA 혼합물을 증류수에 믹스 후 상기 PLLA 제조단계의 PLLA 혼합물에 주입하고 혼합하여 주사기로 뽑아 시술할 수 있도록 하는 혼합 단계;
를 포함하여 수행하는 것을 특징으로 하는 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법.
A PLLA mixture which is prepared by mixing CMC (carboxymethyl cellulose) and mannitol in PLLA (lysoic acid), freeze-drying, pulverizing to a predetermined size, and vial-sterilizing gamma- A manufacturing step;
HA (hyaluronic acid) is mixed with BDDE (butanediol diglycidyl ether) cross-linking agent and gelated. After washing with phosphate buffer, homogeneous cross-linked HA is obtained, filled in vials and autoclaved. HA mixture to produce a HA mixture;
Mixing the HA mixture in the HA mixture preparation step with distilled water, injecting the mixture into the PLLA mixture in the PLLA preparation step, mixing and injecting the mixture with a syringe;
The method of producing a polylactic acid filler and a hyaluronic acid filler conjugate according to claim 1,
청구항 1에 있어서,
상기 PLLA 혼합물 제조단계는,
동결건조의 초기 동결온도는 영하 60~100도 사이가 되도록 하고, 추후 건조온도는 15~25도에서 5일~10일 동안 건조되도록 하고, 분쇄한 입자의 크기는 30um~100um의 범위 이내가 되도록 하는 것을 특징으로 하는 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법.
The method according to claim 1,
Wherein the PLLA mixture preparation step comprises:
The initial freezing temperature of the freeze-drying is set to be in the range of minus 60 to 100 ° C, the drying temperature is 15 ° to 25 ° C for 5 days to 10 days, and the size of the pulverized particles is within a range of 30 to 100 μm Wherein the polylactic acid filler and the hyaluronic acid filler conjugate are prepared.
청구항 1에 있어서,
상기 HA 혼합물 제조단계는,
인산완충액은 HA 100gram 당 30~80리터를 사용하도록 하고, 80~120메쉬의 크기로 통과시켜 균일한 입자의 가교 HA를 얻는 것을 특징으로 하는 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법.
The method according to claim 1,
The HA mixture preparation step comprises:
Wherein the phosphate buffer solution is used in an amount of 30 to 80 liters per 100 grams of HA, and is passed through a size of 80 to 120 mesh to obtain HA of uniform particle cross-linked HA and method for producing a hyaluronic acid filler conjugate.
청구항 1에 있어서,
상기 혼합 단계는,
페이스용의 HA를 제조할 경우 HA 10cc 당 증류수 15~25cc를 사용하고, 바디용의 HA를 제조할 경우 HA 10cc 당 증류수 25~35cc를 사용하는 것을 특징으로 하는 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법.
The method according to claim 1,
Wherein the mixing step comprises:
Characterized in that 15 to 25 cc of distilled water per 10 cc of HA is used when preparing HA for face and 25 to 35 cc of distilled water per 10 cc of HA when preparing HA for body, ≪ / RTI >
청구항 1 내지 청구항 4 중 어느 하나의 청구항에 있어서,
상기 혼합 단계는,
HA 혼합물을 PLLA 혼합물에 주입한 후 3~8분간 흔들어주는 단계를 포함하여 수행하는 것을 특징으로 하는 폴리엘락틱산 필러와 히알루론산 필러 결합체의 제조방법.The method according to any one of claims 1 to 4,
Wherein the mixing step comprises:
HA mixture into a PLLA mixture, followed by shaking for 3 to 8 minutes. The polylactic acid filler and the hyaluronic acid filler conjugate according to claim 1,
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