KR20240039186A - 제형 및 이의 용도 - Google Patents
제형 및 이의 용도 Download PDFInfo
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- KR20240039186A KR20240039186A KR1020247007301A KR20247007301A KR20240039186A KR 20240039186 A KR20240039186 A KR 20240039186A KR 1020247007301 A KR1020247007301 A KR 1020247007301A KR 20247007301 A KR20247007301 A KR 20247007301A KR 20240039186 A KR20240039186 A KR 20240039186A
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- South Korea
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Abstract
본 발명은 경구 투여를 위한 안정한 고형 약학적 제형을 제공한다. 제형은 적어도 하나의 구획을 형성하는 기질 및 구획 내에 적재된 약물 내용물을 포함한다. 제형은 약물 내용물의 활성 약학적 성분이 제어된 방식으로 방출되도록 디자인된다.
Description
본 발명은 일반적으로 생물학적 활성제, 진단제, 시약, 화장품 및 농약/살충제의 약학적 제형 및 제어된 방출에 관한 것이다.
의약품은 시중에 판매되기 위해서는 제형으로 제조되어야 한다. 통상적인 제형은 전형적으로 캡슐 외피와 같은 다른 재사용 불가능한 재료와 함께 활성 약학적 성분 및 비활성 구성요소(부형제)의 혼합물을 포함한다. 제형의 종류는 액체 제형(예를 들어, 용액, 시럽, 엘릭서제, 현탁액 및 유화액), 고체 제형(예를 들어, 정제, 캡슐, 캐플릿 및 겔-캡), 및 반-고체 제형(예를 들면, 연고 및 좌약)을 포함하며, 이들 중에서 고체 제형은 경구 투여를 통해 전신 효과로 약물을 투여하는데 더욱 유리하다.
정제는 제조, 포장 및 선적의 측면에서보다 많은 이점을 나타내고, 식별하고 삼키는 것이 용이한 가장 일반적으로 사용되는 고체 제형이다. 살아있는 유기체로 투여된 후, 정제는 약효를 발휘할 때 신체와 상호작용을 한다. 활성 약학적 성분은 혈액 순환에 흡수되기 전에 정제로부터 배출되어야 한다. 그런 후에 약학적 성분은 신체의 체액 및 조직 전체에서 분산, 분해 또는 용해된다. 약물 흡수, 사용, 신진 대사 및 제거 과정 동안, 제형은 약물의 방출 프로파일 및 생체 이용률을 결정하는데 중요한 역할을 한다.
따라서, 바람직한 약물 혈장 수준, 감소된 부작용뿐만 아니라 개선된 환자 순응도를 제공할 수 있는 제어된 약물 전달 시스템을 제공하는 제형의 개발이 계속 요구되고 있다.
한 양태에서, 본 발명은 적어도 하나의 구획을 형성하는 기질 및 구획 속에 적재된 약물 내용물을 포함하는 제형을 제공한다. 특정 실시태양에서, 약물 내용물은 기질에 작동 가능하게 연결된다. 특정 실시태양에서, 약물 내용물은 기질로부터 분리되고 구획에서 자유롭게 움직일 수 있다.
특정 실시태양에서, 기질은 친수성 폴리머, 소수성 폴리머, 팽창성 폴리머, 비 팽창성 폴리머, 다공성 폴리머, 비 다공성 폴리머, 침식성 폴리머, 비 침식성 폴리머로 이루어진 그룹으로부터 선택된 열가소성 재료로 제조된다. 특정 실시태양에서, 열가소성 재료는 폴리바이닐 카프로락탐-폴리바이닐 아세테이트-폴리에틸렌 글리콜 그래프트 코폴리머 57/30/13, 폴리바이닐피롤리돈-코-바이닐-아세테이트 (PVP-VA), 폴리바이닐피롤리돈-폴리바이닐 아세테이트 코폴리머(PVP-VA) 60/40, 폴리바이닐피롤리돈(PVA), 폴리바이닐 아세테이트(PVAc) 및 폴리바이닐 피롤리돈(PVA) 80/20, 폴리에틸렌 글리콜-폴리바이닐 알코올 그래프트 코폴리머 25/75, 콜리코트 IR-폴리바이닐 알코올 60/40, 폴리바이닐 알코올(PVA 또는 PV-OH), 폴리(바이닐 아세테이트)(PVAc), 폴리(부틸 메타크릴레이트-코-(2-다이메틸아미노에틸)메타크릴레이트-코-메틸 메타크릴레이트) 1:2:1, 폴리(다이메틸아미노에틸메타크릴 레이트-코-메타크릴 에스터), 폴리(에틸 아크릴레이트-코-메틸 메타크릴레이트-코-트라이메틸아모니오에틸 메타크릴레이트 클로라이드), 폴리(메틸 아크릴레이트-코-메틸 메타크릴레이트-코-메타크릴산) 7:3:1, 폴리(메타크릴산-코-메틸메타크릴레이트) 1:2, 폴리(메타크릴산-코-에틸 아크릴레이트) 1:1, 폴리(메타크릴산-코-메틸 메타크릴레이트) 1:1, 폴리(에틸렌 옥사이드)(PEO), 폴리(에틸렌 글리콜)(PEG), 다분기 폴리에스터아마이드, 하이드록시프로필 메틸셀룰로오스 프탈레이트, 하이프로멜로오스 프탈레이트, 하이드록시프로필 메틸셀룰로오스 또는 하이프로멜로오스(HMPC), 하이드록시프로필 메틸셀룰로오스 아세테이트 숙시네이트 또는 하이프로멜로오스 아세테이트 숙시네이트(HPMCAS), 폴리(락티드-코-글리콜라이드)(PLGA), 카보머, 폴리(에틸렌-코-바이닐 아세테이트), 에틸렌-바이닐 아세테이트 코폴리머, 폴리에틸렌(PE) 및 폴리카프로락톤(PCL), 하이드록시 프로필 셀룰로오스(HPC), 폴리옥실 40 수소화 캐스터유, 메틸 셀룰로오스(MC), 에틸 셀룰로오스(EC), 폴록사머, 하이드록시프로필 메틸셀룰로오스 프탈레이트(HPMCP), 폴록사머, 수소화 캐스터유 및 대두유, 글리세릴 팔미토스테아레이트, 카나우바 왁스, 폴리락트산(PLA), 폴리글리콜산(PGA), 셀룰로오스 아세테이트 부티레이트(CAB), 콜로이드성 실리콘, 이산화물, 수크로오스, 글루코오스, 폴리바이닐 아세테이트 프탈레이트(PVAP) 및 이의 조합으로 이루어진 그룹으로부터 선택된다.
특정 실시태양에서, 구획은 원형, 원뿔형, 피라미드형, 원통형, 입방체형 또는 직육면체형, 삼각형 또는 다각형 프리즘형, 사면체형 및 이의 조합으로 이루어진 그룹으로부터 선택된 형상을 갖는다.
특정 실시태양에서, 제 1 약물 내용물은 나노입자, 미세바늘 형태이거나 그물을 형성한다.
특정 실시태양에서, 약물 내용물은 활성 약학적 성분(API)을 포함한다. 특정 실시태양에서, API는 국소 마취제, 항간질제 및 항경련제, 항알츠하이머제, 진통제, 항통풍제, 항고혈압제, 항부정맥제, 이뇨제, 간 질환 치료제, 췌장 질환 치료제, 항히스타민제, 항알레르기제, 글루코코르티코이드제, 호르몬제 및 피임약, 혈당 강하제, 항골다공증제, 항생제, 설폰아마이드, 퀴놀론 및 기타 합성 항균제, 항 결핵제, 항바이러스제, 항염증제, 항종양제, 면역 조절제, 미용 활성제 및 전통 중국 의약으로 이루어진 그룹으로부터 선택된다. 특정 실시태양에서, API는 생물학적 활성제, 진단제, 과학적 연구를 위한 시약, 화장품제 또는 농약제/살충제이다.
특정 실시태양에서, 약물 내용물은 부형제를 추가로 포함한다. 특정 실시태양에서, 부형제는 코코아 버터, 폴리에틸렌 글리콜(PEG), 수크로오스, 글루코오스, 갈락토오스, 프룩토오스, 자일로스락토오스, 말토오스, 트레할로스, 소르비톨, 만니톨, 말토덱스트린, 라피노오스, 스타키로오스, 프룩토-올리고사카라이드, 수용성 올리고머 및 폴리머 및 이의 조합으로 이루어진 그룹으로부터 선택된 재료로 제조된다.
특정 실시태양에서, 구획은 플러그에 의해 차단 및/또는 밀봉되는 구멍을 갖는다. 특정 실시태양에서, 플러그는 다공성 폴리머, 침식성 폴리머, pH 민감성 폴리머 또는 쉘락과 같은 천연 발생 재료로 제조된다. 특정 실시태양에서, 플러그는 수용성 폴리머, 침식성 또는 용해성 폴리머, 왁스 유사 재료 또는 사카라이드 또는 상기한 임의의 재료로 이루어진 그룹으로부터 선택된 재료로 제조된다.
특정 실시태양에서, 제형은 제 1 구획 내에 적재된 가스 생성 구성요소를 포함한다. 특정 실시태양에서, 가스 생성 구성요소는 수용성 탄산염, 아황산염, 중탄산염, 탄산나트륨, 중탄산나트륨, 메타이아황산나트륨, 탄산칼슘 및 이의 조합으로 이루어진 그룹으로부터 선택되며, 이들은 위액과 접촉하여 이산화탄소 또는 이산화황 가스를 배출한다. 특정 실시태양에서, 가스 생성 구성요소는 중탄산 나트륨 및 유기산(예를 들어, 시트르산, 타르타르산 등)의 조물이다.
또 다른 양태에서, 본 발명은 적어도 제 1 구획 및 제 2 구획을 형성하는 기질을 포함하는 제형을 제공한다. 제형은 제 1 구획 내에 적재된 제 1 약물 내용물 및 제 2 구획 내에 적재된 제 2 약물 내용물을 포함한다.
특정 실시태양에서, 제 1 구획과 제 2 구획은 연결된다. 특정 실시태양에서, 제 1 구획과 제 2 구획은 분리된다.
특정 실시태양에서, 제 1 약물 내용물은 제 2 약물 내용물과 동일하다. 특정 실시태양에서, 제 1 약물 내용물은 제 2 약물 내용물과 상이하다.
특정 실시태양에서, 제 1 구획은 제 1 플러그에 의해 덮인 제 1 구멍을 갖고, 제 2 구획은 제 2 플러그에 의해 덮인 제 2 구멍을 갖는다. 특정 실시태양에서, 제 1 플러그는 제 2 플러그보다 더 투과성이 있다. 특정 실시태양에서, 제 1 플러그는 제 2 플러그보다 더 빨리 침식된다.
특정 실시태양에서, 제 1 구획은 제 1 벽으로 둘러싸여 있고 제 2 구획은 제 2 벽으로 둘러싸여 있다.
특정 실시태양에서, 제 1 벽은 제 2 벽보다 두껍다. 특정 실시태양에서, 제 1 벽은 제 2 벽보다 침투성이 있다. 특정 실시태양에서, 제 1 벽은 제 2 벽보다 빠르게 침식된다.
본 발명의 내용 중에 포함된다.
도 1a는 약물 내용물을 포함하는 통상적인 제형을 도시한다.
도 1b는 대상에게 투여될 때 도 1a의 제형의 방출 프로파일을 예시한다.
도 1c는 도 1a의 제형이 대상에게 투여될 때 혈장 약물 수준을 도시한다.
도 1d는 대상에게 투여될 때 0차 약물 방출 프로파일을 갖는 제어된 방출 제형의 혈장 약물 수준을 도시한다.
도 2a는 구획을 형성하는 기질을 가지며 약물 내용물이 구획 내에 적재된 예시적인 제형을 도시한다.
도 2b는 도 2a에 예시된 제형으로부터 API의 방출을 도시한다.
도 3은 구획을 형성하는 기질을 가지며 약물 내용물이 구획 내에 적재된 예시적 제형을 도시한다.
도 4a는 원형의 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 4b는 다양한 크기의 개구부를 포함하는 여러 구획을 형성하는 기판을 갖는 예시적인 제형을 도시한다.
도 4c는 각진 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 4d는 상이한 크기의 반경의 여러 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 4e는 API의 방출 속도를 조절하는데 사용될 수 있는 상이한 기하학적 형태의 여러 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 5는 원형 구획을 갖는 예시적인 제형의 단면을 도시한다.
도 6은 층들을 형성하는 기질을 가지며 나노입자 형태의 약물 내용물이 층들 사이에 분산된 예시적 제형을 도시한다.
도 7은 구획을 형성하는 기질을 가지며 미세바늘 형상의 약물 내용물이 구획 내에 적재된 예시적인 제형을 도시한다.
도 8a는 약물 내용물이 적재된 구획을 형성하는 기질을 갖는 예시적 제형을 도시한다. 약물 내용물은 네트워크를 형성한다. 기질은 1-5분 사이에 용해되는 재료로 제조되며, 약물 내용물은 초 단위로 용해된다.
도 8b는 도 8a에 예시된 제형으로부터 API의 신속한 방출을 도시한다.
도 9는 복수의 컬럼 형상 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 하나의 약물 내용물이 적재된다. 약물 내용물의 방출은 구획의 수와 크기에 의해 제어될 수 있다.
도 10a는 3개의 컬럼 형상 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 하나의 약물 내용물이 적재된다. 각 약물 내용물은 각 구획의 구멍을 막는 마개를 가진다.
도 10b는 여러 층을 가진 기질을 가지며 각 층에 삽입된 약물 내용물을 갖는 예시적 제형을 도시한다.
도 10c는 도 10a 또는 10b에 예시된 제형으로부터 약물 내용물의 필연적인 방출을 도시한다.
도 10d는 대상에게 투여될 때 도 10a 또는 10b에 예시된 제어된 방출 제형의 혈장 약물 수준을 도시한다.
도 11은 환자 특이적 제형을 제조하기 위해 3차원 프린터의 사용을 위한 개략적인 작업 흐름도이다.
도 12a는 3층 기질을 가지며 상이한 약물 내용물이 각 층에 삽입된 예시적인 제형을 도시한다.
도 12b는 도 12a에 예시된 제형으로부터 3개 API의 방출을 예시한다.
도 13a는 3개 구획을 형성하는 기질을 가지며, 이의 각각에 하나의 약물 내용물이 적재된 예시적인 제형을 도시한다. 약물 내용물의 방출 프로파일은 약물 내용물의 용해 속도에 의해 제어될 수 있다.
도 13b는 도 13a에 예시된 제형으로부터 API의 방출 프로파일을 예시한다.
도 14a는 3개 원형 세그먼트를 가진 기질을 가지며, 약물 내용물이 각 세그먼트 내에 삽입된 예시적인 제형을 도시한다.
도 14b는 외피 구조로 감싸진 3개 원형 세그먼트를 가진 기질을 갖는 예시적인 제형을 도시한다.
도 14c는 도 8a 및 도 8b에 예시된 제형으로부터 API의 방출 프로파일을 도시한다.
도 15a는 약물 내용물로 채워진 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 제 2 API는 기질에 삽입되어 기질이 용해될 때 방출된다.
도 15b는 도 15a에 예시된 제형으로부터 API의 제어된 방출을 도시한다.
도 16a는 3개의 컬럼 형상 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 하나의 약물 내용물이 적재된다. 각 약물 내용물은 각 구획의 개구부를 봉쇄하는 플러그를 가진다. 각 구획에서 약물 내용물의 방출은 플러그의 침투성, 분해성 또는 침식성에 의해 제어될 수 있다.
도 16b는 도 16a에 예시된 제형으로부터 API의 방출 프로파일을 도시한다.
도 17a는 4개의 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 약물 내용물이 적재된다.
도 17b는 4개의 약물 내용물이 삽입된 세그먼트롤 이루어진 기질을 갖는 제형으로부터 API의 방출 프로파일을 도시한다.
도 17c는 도 17a에 예시된 제형으로부터 API의 제어된 방출을 도시한다.
도 18a는 원형 구획을 형성하는 기질을 갖는 제형의 개략도이다.
도 18b는 도 18a에 예시된 제형의 약물 방출 과정의 사진이다.
도 18c는 도 18a의 제형으로부터 벤조산 및 PEG8000의 방출 백분율 곡선을 도시한다.
도 19a는 2개의 구획을 포함하는 제형의 사시도를 도시한다.
도 19b는 도 19a의 제형의 단면도를 도시한다.
도 19c는 도 19a의 제형의 예시적인 방출 프로파일을 도시한다.
도 19d는 도 19a의 제형의 다른 예시적인 방출 프로파일을 도시한다.
도 1b는 대상에게 투여될 때 도 1a의 제형의 방출 프로파일을 예시한다.
도 1c는 도 1a의 제형이 대상에게 투여될 때 혈장 약물 수준을 도시한다.
도 1d는 대상에게 투여될 때 0차 약물 방출 프로파일을 갖는 제어된 방출 제형의 혈장 약물 수준을 도시한다.
도 2a는 구획을 형성하는 기질을 가지며 약물 내용물이 구획 내에 적재된 예시적인 제형을 도시한다.
도 2b는 도 2a에 예시된 제형으로부터 API의 방출을 도시한다.
도 3은 구획을 형성하는 기질을 가지며 약물 내용물이 구획 내에 적재된 예시적 제형을 도시한다.
도 4a는 원형의 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 4b는 다양한 크기의 개구부를 포함하는 여러 구획을 형성하는 기판을 갖는 예시적인 제형을 도시한다.
도 4c는 각진 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 4d는 상이한 크기의 반경의 여러 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 4e는 API의 방출 속도를 조절하는데 사용될 수 있는 상이한 기하학적 형태의 여러 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
도 5는 원형 구획을 갖는 예시적인 제형의 단면을 도시한다.
도 6은 층들을 형성하는 기질을 가지며 나노입자 형태의 약물 내용물이 층들 사이에 분산된 예시적 제형을 도시한다.
도 7은 구획을 형성하는 기질을 가지며 미세바늘 형상의 약물 내용물이 구획 내에 적재된 예시적인 제형을 도시한다.
도 8a는 약물 내용물이 적재된 구획을 형성하는 기질을 갖는 예시적 제형을 도시한다. 약물 내용물은 네트워크를 형성한다. 기질은 1-5분 사이에 용해되는 재료로 제조되며, 약물 내용물은 초 단위로 용해된다.
도 8b는 도 8a에 예시된 제형으로부터 API의 신속한 방출을 도시한다.
도 9는 복수의 컬럼 형상 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 하나의 약물 내용물이 적재된다. 약물 내용물의 방출은 구획의 수와 크기에 의해 제어될 수 있다.
도 10a는 3개의 컬럼 형상 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 하나의 약물 내용물이 적재된다. 각 약물 내용물은 각 구획의 구멍을 막는 마개를 가진다.
도 10b는 여러 층을 가진 기질을 가지며 각 층에 삽입된 약물 내용물을 갖는 예시적 제형을 도시한다.
도 10c는 도 10a 또는 10b에 예시된 제형으로부터 약물 내용물의 필연적인 방출을 도시한다.
도 10d는 대상에게 투여될 때 도 10a 또는 10b에 예시된 제어된 방출 제형의 혈장 약물 수준을 도시한다.
도 11은 환자 특이적 제형을 제조하기 위해 3차원 프린터의 사용을 위한 개략적인 작업 흐름도이다.
도 12a는 3층 기질을 가지며 상이한 약물 내용물이 각 층에 삽입된 예시적인 제형을 도시한다.
도 12b는 도 12a에 예시된 제형으로부터 3개 API의 방출을 예시한다.
도 13a는 3개 구획을 형성하는 기질을 가지며, 이의 각각에 하나의 약물 내용물이 적재된 예시적인 제형을 도시한다. 약물 내용물의 방출 프로파일은 약물 내용물의 용해 속도에 의해 제어될 수 있다.
도 13b는 도 13a에 예시된 제형으로부터 API의 방출 프로파일을 예시한다.
도 14a는 3개 원형 세그먼트를 가진 기질을 가지며, 약물 내용물이 각 세그먼트 내에 삽입된 예시적인 제형을 도시한다.
도 14b는 외피 구조로 감싸진 3개 원형 세그먼트를 가진 기질을 갖는 예시적인 제형을 도시한다.
도 14c는 도 8a 및 도 8b에 예시된 제형으로부터 API의 방출 프로파일을 도시한다.
도 15a는 약물 내용물로 채워진 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 제 2 API는 기질에 삽입되어 기질이 용해될 때 방출된다.
도 15b는 도 15a에 예시된 제형으로부터 API의 제어된 방출을 도시한다.
도 16a는 3개의 컬럼 형상 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 하나의 약물 내용물이 적재된다. 각 약물 내용물은 각 구획의 개구부를 봉쇄하는 플러그를 가진다. 각 구획에서 약물 내용물의 방출은 플러그의 침투성, 분해성 또는 침식성에 의해 제어될 수 있다.
도 16b는 도 16a에 예시된 제형으로부터 API의 방출 프로파일을 도시한다.
도 17a는 4개의 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 약물 내용물이 적재된다.
도 17b는 4개의 약물 내용물이 삽입된 세그먼트롤 이루어진 기질을 갖는 제형으로부터 API의 방출 프로파일을 도시한다.
도 17c는 도 17a에 예시된 제형으로부터 API의 제어된 방출을 도시한다.
도 18a는 원형 구획을 형성하는 기질을 갖는 제형의 개략도이다.
도 18b는 도 18a에 예시된 제형의 약물 방출 과정의 사진이다.
도 18c는 도 18a의 제형으로부터 벤조산 및 PEG8000의 방출 백분율 곡선을 도시한다.
도 19a는 2개의 구획을 포함하는 제형의 사시도를 도시한다.
도 19b는 도 19a의 제형의 단면도를 도시한다.
도 19c는 도 19a의 제형의 예시적인 방출 프로파일을 도시한다.
도 19d는 도 19a의 제형의 다른 예시적인 방출 프로파일을 도시한다.
상기 발명의 요약 및 발명의 상세한 설명, 및 이하의 청구 범위 및 첨부 도면에서, 본 발명의 특정한 특징(방법 단계 포함)이 참조된다. 본 명세서에서 본 발명의 설명은 이런 특정한 특징의 모든 가능한 조합을 포함하는 것으로 이해된다. 예를 들어, 특정한 특징이 본 발명의 특정한 양태 또는 실시태양의 문맥 또는 특정한 청구항에 개시되어있는 경우, 그 특징은 가능한 한도 내에서 본 발명의 다른 특정의 양태 및 실시태양의 조합 및/또는 문맥에서 및 일반적으로 본 발명에서 사용될 수 있다.
용어 "포함한다" 및 이의 문법적 등가물은 본 명세서에서 다른 구성요소, 성분, 단계 등이 임의로 존재함을 의미하는 것으로 사용된다. 예를 들어, 성분 A, B 및 C를 "포함하는" (또는 "포함하는") 물품은 성분 A, B 및 C로 구성될 수 있거나 (즉, 단지 함유한다), 또는 성분 A, B 및 C뿐만 아니라 C뿐만 아니라 하나 이상의 다른 구성요소를 포함할 수 있다.
여기에서 둘 이상의 정의된 단계를 포함하는 방법이 언급되는 경우, 정의된 단계는 임의의 순서 또는 동시에(문맥이 그 가능성을 배제하는 경우를 제외하고) 수행될 수 있고, 상기 방법은 하나 이상의 다른 단계 정의된 단계들 중 두 단계 사이에서, 또는 정의된 모든 단계 후에 수행된다(문맥이 그 가능성을 배제한 경우 제외).
값의 범위가 제공되는 경우, 문맥상 명확하게 달리 지시되지 않는 한, 그 범위 및 상기 범위에서 임의의 다른 명시된 또는 개재된 값의 상한 및 하한 사이에서 각각의 개재된 값, 하한 단위의 1/10까지는 명시된 범위에서 특별히 배제된 한계를 조건으로 하여 본 발명 내에 포함된다. 명시된 범위가 한계의 하나 또는 모두를 포함하는 경우, 이런 포함된 한계의 하나 또는 모두를 제외한 범위도 또한 본 발명에 포함된다.
숫자 앞의 용어 "적어도"는 그 번호로 개시되는 범위의 시작을 나타내기 위해 본 명세서에서 사용된다(정의되는 변수에 따라 상한을 갖는 또는 상한이 없는 범위일 수 있음). 예를 들어, "적어도 1"은 1 또는 1보다 큰 것을 의미한다. 숫자 앞의 용어 "최대"는 그 번호로 끝나는 범위의 끝을 나타내기 위해 본 명세서에서 사용된다(정의된 변수에 따라 하한 또는 하한이 없는 범위로서 1 또는 0을 갖는 범위일 수 있음). 예를 들어 "최대 4"는 4 또는 4 미만을 의미하고 "최대 40 %"는 40% 또는 40% 미만을 의미한다. 본 발명에서, 범위가 "(제 1 숫자) 내지 (제 2 숫자)" 또는 "(제 1 숫자)-(제 2 숫자)"로 주어지면, 이는 하한이 제 1 숫자이고 상한이 제 2 숫자인 범위를 의미한다. 예를 들어 2 내지 10 밀리미터는 하한이 2 밀리미터이고 상한이 10 밀리미터인 범위를 의미한다.
설명의 간단함과 명확함을 위해, 적절한 경우, 대응하는 또는 유사한 요소를 나타내기 위해 다른 도면에서 참조 번호가 반복되어 있음을 알 수 있다. 또한, 본 발명에 설명된 실시태양들의 완전한 이해를 제공하기 위해 다수의 특정 세부사항이 제시된다. 그러나, 본 발명에 기술된 실시태양은 이러한 특정 세부사항 없이도 실시될 수 있다. 다른 예에서, 방법, 절차 및 구성요소는 기술된 관련 기능을 모호하게하지 않도록 상세히 설명하지 않았다. 또한, 설명은 본 발명에 기술된 구현의 범위를 제한하는 것으로 간주되어서는 안 된다. 본 발명에 개시된 실시태양들의 설명 및 특징은 다른 언급이 없는 한, 상호 배타적인 것으로 간주되어서는 안 됨을 이해할 것이다.
제어 방출 제형
통상적인 고체 제형, 예컨대 압축된 정제는 활성 약물 성분이 용해되거나 삽입된 기질로 구성된다(도 1a). 현재 통상적인 고체 제형은 약물의 혈장 수준이 투여 후 상당히 높은 수준으로 급격히 증가한 다음 지수적으로 감소하는 1차 약물 방출 프로파일(도 1b)을 나타낸다(도 1c 참조). 이는 약물 농도 감소 또는 고농도에서 발생할 수 있는 약물 독성으로 인한 최소 치료 효능과 같은 단점을 가지고 있다. 이 유형의 약물 방출은 적절한 혈장 약물 수준 균형을 허용하지 않는다. 본 발명은 증가된 환자 순응도, 선택적 약리학적 작용, 감소된 부작용 및 감소된 투여 빈도를 포함하는 종래 시스템에 비해 이점을 제공하는 변형 또는 제어 방출 경구 약물 전달 시스템에 관한 것이다. 제어 방출은 치료 범위 내에서 약물의 장기 전달 및 혈장 수준의 유지를 제공한다. 예를 들어, 0차 약물 방출 프로파일(도 1d)을 나타내는 약물 전달 시스템은 일정한 양의 약물이 장시간에 걸쳐 방출되어 균일하고 지속적인 약물 전달을 가능하게 한다. 결과적으로, 0차 방출 프로파일은 항생제 전달, 고혈압 치료, 통증 관리, 항우울제 전달 및 일정한 혈장 약물 농도를 필요로 하는 수많은 다른 조건에서 바람직할 수 있다.
따라서, 본 발명의 한 양태는 제어된 방출 프로파일을 갖는 경구 투여용 안정한 고체 약학적 제형을 제공한다. 특정 실시태양에서, 제형은 하나 이상의 구획을 형성하는 기질 및 구획 내에 적재된 약물 내용물을 포함한다. 제형은 약물 내용물의 활성 약학적 성분의 방출이, 예를 들어 소정 방법으로 구획을 개방함으로써 제어될 수 있도록 설계된다.
A. 기질
본 발명에 사용된 바와 같이, "기질"은 약물이 둘러싸이거나 삽입된 구조를 의미한다. 본 발명의 제형의 기질은 경구 투여에 적합한 임의의 크기 및 형태일 수 있다. 특정 실시태양에서, 기질은 약 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm 및 12mm의 직경을 갖는 편평한 원형 정제이다. 특정 실시태양에서, 기질은 a mm x b mm의 치수를 갖는 타원형 정제이며, a는 5 내지 15이고, b는 2 내지 10이다. 특정 실시태양에서, 기질은 캡슐 형태를 갖는다.
특정 실시태양에서, 기질은 친수성 폴리머(예를 들어, 하이드록시 프로필 메틸 셀룰로오스(HPMC) 및 폴리(에틸렌 옥사이드)(PEO)), 소수성 폴리머(예를 들어, 에틸 셀룰로오스(EC)), 팽창성 폴리머, 비 팽창성 폴리머, 다공성 폴리머, 비 다공성 폴리머, 침식성 폴리머, 또는 비 침식성 폴리머로 제조된다.
특정 실시태양에서, 제형은 모놀리스 기질을 갖는다. 특정 실시태양에서, 기질은 수 개의 조각으로 이루어지며, 각 조각은 동일하거나 상이한 재료로 제조된다.
특정 실시태양에서, 기질은 열가소성 재료로 제조된다. 본 발명에 사용된 바와 같이, "열가소성 재료"는 열 및 압력을 사용하여 성형될 수있는 능력을 갖는 재료를 의미한다. 특정 실시태양에서, 열가소성 재료는, 예를 들어, 약물 내용물 방출이 주로 확산에 의해 진행되는 친수성 겔 형성 재료 또는 약물 내용물 방출이 주로 기질의 기공으로부터의 확산에 의해 진행되는 소수성 재료일 수 있다. 폴리머, 특히 셀룰로스 에터, 셀룰로오스 에스터 및/또는 아크릴 수지가 친수성 열가소성 재료로서 사용될 수 있다. 에틸셀룰로오스, 하이드록시프로필메틸셀룰로오스, 하이드록시프로필셀룰로오스, 하이드록시메틸셀룰로오스, 폴리(메트)아크릴산 및/또는 이의 염, 아마이드 또는 에스터와 같은 이의 유도체는 열가소성 재료로서 사용하기에 적합하다. C12-C30 지방산 및/또는 C12-C30 지방 알코올의 모노- 또는 다이글리세라이드 및/또는 왁스 또는 이의 혼합물과 같은 당업자에게 공지된 생리학적으로 허용가능한 소수성 재료가 열가소성 재료로서 사용될 수 있다. 소수성 폴리머, 왁스, 지방, 장쇄 지방산, 지방 알코올 또는 상응하는 에스터 또는 에터 또는 이들의 혼합물과 같은 소수성 재료로부터 제조된 기질도 또한 고려된다.
특정 실시태양에서, 열가소성 재료는 폴리바이닐 카프로락탐-폴리바이닐 아세테이트-폴리에틸렌 글리콜 그래프트 코폴리머 57/30/13, 폴리바이닐피롤리돈-코-바이닐-아세테이트 (PVP-VA), 폴리바이닐피롤리돈-폴리바이닐 아세테이트 코폴리머(PVP-VA) 60/40, 폴리바이닐피롤리돈(PVA), 폴리바이닐 아세테이트(PVAc) 및 폴리바이닐 피롤리돈(PVA) 80/20, 폴리에틸렌 글리콜-폴리바이닐 알코올 그래프트 코폴리머 25/75, 콜리코트 IR-폴리바이닐 알코올 60/40, 폴리바이닐 알코올(PVA 또는 PV-OH), 폴리(바이닐 아세테이트)(PVAc), 폴리(부틸 메타크릴레이트-코-(2-다이메틸아미노에틸)메타크릴레이트-코-메틸 메타크릴레이트) 1:2:1, 폴리(다이메틸아미노에틸메타크릴 레이트-코-메타크릴 에스터), 폴리(에틸 아크릴레이트-코-메틸 메타크릴레이트-코-트라이메틸아모니오에틸 메타크릴레이트 클로라이드), 폴리(메틸 아크릴레이트-코-메틸 메타크릴레이트-코-메타크릴산) 7:3:1, 폴리(메타크릴산-코-메틸메타크릴레이트) 1:2, 폴리(메타크릴산-코-에틸 아크릴레이트) 1:1, 폴리(메타크릴산-코-메틸 메타크릴레이트) 1:1, 폴리(에틸렌 옥사이드)(PEO), 폴리(에틸렌 글리콜)(PEG), 다분기 폴리에스터아마이드, 하이드록시프로필 메틸셀룰로오스 프탈레이트, 하이프로멜로오스 프탈레이트, 하이드록시프로필 메틸셀룰로오스 또는 하이프로멜로오스(HMPC), 하이드록시프로필 메틸셀룰로오스 아세테이트 숙시네이트 또는 하이프로멜로오스 아세테이트 숙시네이트(HPMCAS), 폴리(락티드-코-글리콜라이드)(PLGA), 카보머, 폴리(에틸렌-코-바이닐 아세테이트), 에틸렌-바이닐 아세테이트 코폴리머, 폴리에틸렌(PE) 및 폴리카프로락톤(PCL), 하이드록시 프로필 셀룰로오스(HPC), 폴리옥실 40 수소화 캐스터유, 메틸 셀룰로오스(MC), 에틸 셀룰로오스(EC), 폴록사머, 하이드록시프로필 메틸셀룰로오스 프탈레이트(HPMCP), 폴록사머, 수소화 캐스터유 및 대두유, 글리세릴 팔미토스테아레이트, 카나우바 왁스, 폴리락트산(PLA), 폴리글리콜산(PGA), 셀룰로오스 아세테이트 부티레이트(CAB), 콜로이드성 실리콘, 이산화물, 수크로오스, 글루코오스, 폴리바이닐 아세테이트 프탈레이트(PVAP) 및 이의 조합으로 이루어진 그룹으로부터 선택된다.
다양한 열가소성 재료의 특성 및 공급원이 표 1에 나열된다.
특정 실시태양에서, 열가소성 재료는 용융 증착 모델링(FDM)과 같은 부가적인 방법을 사용하여 제형이 제조되도록 한다. 특정 실시태양에서, 기질은 열가소성 재료를 압출하도록 구성된 3차원 프린터(3D 프린터)를 사용하여 제조될 수 있다. 전형적으로, 열가소성 재료는 압출되어 기질을 형성하기 전에 3D 프린터에서 용융된다. 특정 실시태양에서, 적합한 압출기는 압출기 내의 온도가 50℃ 내지 180℃ 및 80℃ 내지 140℃의 범위인 단일 또는 이중 스크류 압출기를 포함하지만 이에 제한되지 않는다. 일반적으로, 압출 공정은 열가소성 재료의 유리 전이 온도(Tg)보다 10°내지 40℃ 높은 온도에서 수행될 수 있다. 3차원 프린터에서 사용하기에 적합한 온도에 도달하면, 열가소성 재료는 3차원 프린팅 표면에 증착될 수 있다. 열가소성 재료에 의해 제조된 기질 및 구획의 형상 및 크기는 3차원 프린팅 공정을 프로그래밍함으로써 제어될 수 있다.
특정 실시태양에서, 기질의 재료는 약물의 방출 프로파일을 제어하도록 선택될 수 있다. 예를 들어, 기질은 원하는 침식/용해 속도, 투과 속도를 갖는 재료로 제조되어 투여될 때 구획이 소정의 방식으로 개방될 수 있고 약물 내용물이 원하는 속도로 구획으로부터 방출된다. 특정 실시태양에서, 기질은 침식성 또는 용해성이며 활성 약학적 성분(API)으로 삽입된다. 기질이 침식되거나 용해될 때 API가 방출된다.
약물 내용물의 방출은 또한 기질의 두께를 조절함으로써 제어될 수 있다. 예를 들어, 구획을 형성하는 기질은 가용성 재료로 제조된다. 구획의 개방, 따라서 구획 내에 담긴 약물 내용물의 방출은 구획을 둘러싸는 벽의 두께를 조절함으로써 제어될 수 있다. 벽이 두꺼울수록 구획이 더 천천히 열리고 약물이 더 느리게 방출된다.
B. 구획
특정 실시태양에서, 본 발명에 개시된 제형은 기질 내에 적어도 하나의 구획을 함유한다. 본 발명에 사용된 바와 같이, "구획"은 기질에 의해 표시되거나 구획 된 장소, 부분 또는 공간을 의미한다. 구획은 폐쇄되거나 개방될 수 있다(예를 들어, 구멍 또는 통로를 가짐). 구획은 약물 내용물을 적재하기에 적합한 임의의 형상일 수 있다. 특정 실시태양에서, 구획은 원형, 원뿔형, 피라미드형, 원통형, 입방체형 또는 직육면체형, 삼각형 또는 다각형 프리즘형, 사면체형 및 이의 조합으로 이루어진 그룹으로부터 선택된 형상을 갖는다.
특정 실시태양에서, 제형에 구획을 함유하는 것은 위장관에서의 보유력을 증가시킬 수 있다. 도 2a는 약물 내용물이 적재되는 구획을 형성하는 기질을 갖는 예시적인 제형을 예시한다. 도 2a를 참조하면, 제형(100)은 기질(101)에 의해 형성된 구획(102)을 갖는다. 약물 내용물(103)은 구획(102)의 내벽에 연결됨으로써 형성된 구획(102)에 적재된다. 구획(102)은 제형에 부유 효과를 제공할 수 있어서 위 또는 수성 또는 산성 환경에서 이의 체류 시간을 연장시킨다. 체류 시간은 기질의 재료의 침식/용해 속도의 함수일 수 있으며 도 2b에 도시된 바와 같이 API의 지속 방출을 초래한다.
도 3은 위장관에서의 체류가 증가된 또 다른 예시적인 제형을 예시한다. 도 3을 참조하면, 제형(200)은 구획(202)이 구획(202) 내에서 자유롭게 움직이는 제 2 제형(203) (예를 들어, 정제)을 함유하는 형태를 갖는다. 제형의 위장 체류 시간은 제한적이다. 부유 시스템을 사용하면 제형이 위에 머무르고 위장관 상부에서 지속적으로 약물을 방출하고 소장에서의 흡수를 극대화할 수 있다.
특정 실시태양에서, 구획의 형상은 독창적으로 만들어져 약물 내용물이 제어 된 속도로 방출될 수 있다. 특정 실시태양에서, 구획은 쐐기형, 원형, 원뿔형, 피라미드형, 원통형, 입방체형 또는 직육면체형, 삼각형 또는 다각형 프리즘형, 사면체형 및 이의 조합으로 이루어진된 그룹으로부터 선택된 형상을 갖는다.
한 실시태양에서, 제형의 구획은 상이한 기하학적 형상을 갖는다. 도 4a는 파이형의 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 도 4b는 다양한 크기의 개구부를 포함하는 기판을 형성하는 다수의 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 도 4c는 각진 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 도 4d는 상이한 크기의 반경을 갖는 다수의 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다.
구획의 형태는 투여 형태의 방출 프로파일을 제어하는데 사용될 수 있다. 예를 들어, R.A. Lipper 및 W.I. Higuichi는 도 5에 예시된 0차 방출 프로파일을 제공하는 전달 시스템을 기술하였다. 도 5는 원형 구획을 갖는 전달 시스템의 단면도를 도시한다. 구획은 작은 입구를 통해 주위와 연결된다. 구획에 용해되어 API를 방출하는 약물 내용물이 적재된다. API는 작은 개구부를 통해 주위로 방출된다. 약물 내용물의 용해 속도는 약물 내용물의 용해 경계(약물 내용물과 구획 사이의 계면)의 면적과 상관 관계가 있다. 반면에, 주위로의 API 확산 속도는 확산 경로 길이 λ와 부정적 상관 관계가있다. 결과적으로, 약물 내용물이 용해됨에 따라, 용해 경계의 면적이 증가하고 약물 내용물의 용해 속도가 증가한다. 한편, 확산 경로 길이 λ는 약물 내용물이 용해됨에 따라 증가한다. 따라서 구획에서 방출된 API는 제형 밖으로 확산되기 위해 더 긴 길이로 운반될 필요가 있다. 제형은 0차 방출 동역학을 제공하도록 설계될 수 있다고 생각된다(R.A. Lipper and W. I. Higuchi (1977) Analysis of theoretical behavior of a proposed zero-order drug delivery system. J. Pharm Sci 66(2): 163-4; D. Brooke and R. J. Washkuhn (1977) Zero-order drug delivery system: theory and preliminary testing. J Pharm Sci. 66(2):159-162).
C. 약물 내용물
본 발명에 사용된 바와 같이, 용어 "약물 내용물"은 활성 약학적 성분(API), 화장품제, 생물학적 제제, 진단제 및 과학 실험용 시약을 포함하는 하나 이상의 활성 성분을 포함하는 조성물을 의미한다.
본 발명에 사용된 바와 같이, API는 생물학적으로 활성인 의약품 내의 성분을 의미한다. 특정 실시태양에서, API는 국소 마취제, 항간질제 및 항경련제, 항알츠하이머제, 진통제, 항통풍제, 항고혈압제, 항부정맥제, 이뇨제, 간 질환 치료제, 췌장 질환 치료제, 항히스타민제, 항알레르기제, 글루코코르티코이드제, 호르몬제 및 피임약, 혈당 강하제, 항골다공증제, 항생제, 설폰아마이드, 퀴놀론 및 기타 합성 항균제, 항 결핵제, 항바이러스제, 항염증제, 항종양제, 면역 조절제, 미용 활성제 및 전통 중국 의약(TCM) 및 TCM 추출물로 이루어진 그룹으로부터 선택된다.
특정 실시태양에서, API는 (R)-폴리틱소린(folitixorin), 리도카인(lidocaine), 11-다이-제2-에틸리놀레이트(11-di-deutero-ethyllinoleate), 16-디하이드로-프레그네놀론(16-dehydro-pregnenolone), 17-베타-에스트라다이올(17-beta-estradiol), 2-이미노비오틴(2-iminobiotin), 3,5-다이요오도티로프로피온산(3,5-diiodothyropropionicacid), 5-플루오로-2-데옥시시티딘(5-fluoro-2-deoxycytidine), 6-머캅토퓨린(6-mercaptopurine), 에도트레오티드(edotreotide), 아바카비르(abacavir), 아발론 헤모시아닌(abalone haemocyanin), 아바메타피르(abametapir), 아베디테롤(abediterol), 아베마시클리브(abemaciclib), 아벡시노스타트(abexinostat), 아비라테론(abiraterone), 아클라브루티닙(acalabrutinib), 아캄프로세이트(acamprosate), 아캄프로세이트칼슘(acamprosatecalcium), 아카보스(acarbose), 아세빌루스타트(acebilustat), 아세클리딘(aceclidine), 아세클로페낙(aceclofenac), 아세히티신 하이드로클로라이드(acehytisine hydrochloride), 아세만난(acemannan), 아세네우람산(aceneuramic acid), 아세트아미노펜(acetaminophen), 아세틸시스테인(acetylcysteine), 아세틸키타사마이신(acetylkitasamycin), 아세틸-L-카르니틴하이드로클로라이드(acetyl-L-carnitinehydrochloride), 아세틸살리실산(acetylsalicylicacid), 아시클로버(aciclovir), 아시피목스(acipimox), 아시타자놀라스트(acitazanolast), 아시트레틴(acitretin), 아클리디늄(aclidinium), 아클리디늄 브로마이드(aclidinium bromide), 아콜비펜(acolbifene), 아코라플록사신(acorafloxacin), 아코티아마이드(acotiamide), 아크리바스틴(acrivastine)，액타리트(actarit)，아다팔렌(adapalene)，아데포비르다이피복실(adefovirdipivoxil)，아데메티오닌(ademetionine)，아도에어(adoair)，아파티닙(afatinib)，아피목시펜(afimoxifene)，아푸레세르티닙(afuresertib)，아고멜라틴(agomelatine)，아일데나필시트레이트(aildenafilcitrate)，알라도리안(aladorian)，알라레보나다이플록사신 메실레이트(alalevonadifloxacin mesylate)，알라렐린 아세테이트(alarelin acetate)，알라트로플록사신 메실레이트(alatrofloxacin mesylate)，알벤다졸(albendazole)，알부테롤 설페이트(albuterol sulfate)，알부터페노이드(albuterpenoids)，알카프타딘(alcaftadine)，알독소루비신(aldoxorubicin)，알렉티닙(alectinib)，알렌드로네이트(alendronate)，알렌드로네이트 소듐(alendronate sodium)，알렌드로네이트 수산화트륨(alendronate sodiumhydrate)，알렌드론산(alendronic acid)，알파칼시돌(alfacalcidol), 알팍살론(alfaxalone)，알펜타닐(alfentanil)，알푸조신(alfuzosin)，알리세르팁(alisertib)，알리스키렌(aliskiren)，알리스포리비르(alisporivir)，알리트레티노인(alitretinoin)，알란토인(allantoin)，알리사르타니소프록실(allisartanisoproxil)，알로푸리놀(allopurinol)，알모트립탄(almotriptan)，알로글립틴(alogliptin)，알로글립틴 벤조에이트(alogliptin benzoate)，알로세트론(alosetron)，알펠리십(alpelisib)，알파케토글루타레이트(alphaketoglutarate)，알피리포산(alphalipoic acid)，알파-란티트립신(alpha-lantitrypsin)，알파-사이클로덱스트린-안정화 설포라페인(alpha-cyclodextrin-stabilized sulforaphane)，알프라졸람(alprazolam)， 알프로스타딜(alprostadil)，알프로스타딜 알파덱스(alprostadil alfadex)，알티라티닙(altiratinib)，알트레타민(altretamine)，알트로페인(altropane)，알루미늄 설페이트(aluminum sulfate)，알비모판(alvimopan)，알보시딥(alvocidib)，아만타딘(amantadine)，아만타딘 하이드로클로라이드(amantadine hydrochloride)，암브리센탄(ambrisentan)，암브록솔(ambroxol)，암브록솔 하이드로클로라이드(ambroxol hydrochloride)，암카세르팁(amcasertib)，암페타민(amfetamine)，암페타민 폴리스티렉스(amfetamine polistirex)，아미팜프리딘(amifampridine)，아미팜프리딘 포스페이트(amifampridine phosphate)，아미포스틴(amifostine)，아미카신(amikacin)，아밀로라이드(amiloride)，아미노레불리닉(aminolevulinic)，아미노레불린산(aminolevulinic acid)，아미노레불린산 하이드로클로라이드(aminolevulinic acid hydrochloride)，아미노프테린(aminopterin)，아미오다론(amiodarone)，아미셀리모드(amiselimod)，아미설프리드(amisulpride)，아미티파딘 하이드로클로라이드(amitifadine hydrochloride)，아미트리프틸린(amitriptyline)，아밀레사녹스(amlexanox)，암로디핀(amlodipine)，암로디핀 베실레이트(amlodipine besilate)，암로디핀 베실레이트(amlodipine besylate)，암로디핀 캄실레이트(amlodipine camsylate)，암로디핀 말레이트(amlodipine maleate)，암로디핀 니코티네이트(amlodipine nicotinate)，암로디핀 오로테이트(amlodipine orotate)，락트산 암모늄(ammonium lactate)， 아모디아퀴인(amodiaquine)，아모롤핀(amorolfine)，아모설라롤(amosulalol)，아목시실린(amoxicillin)，아목시실린 하이드레이트(amoxicillin hydrate)，암페타민(amphetamine)，암페타민 아스파르테이트(amphetamine aspartate)，암페타민 설페이트(amphetamine sulfate)，암포테리신B(amphotericinB)，암포테리신B 클로레스테릴설페이트(amphotericinB cholesterylsulfate)，암포테리신B 지질 복합체(amphotericinB lipid complex)，암피실린 소듐(ampicillin sodium)，암피록시캄(ampiroxicam)，암리논(amrinone)，암루비신(amrubicin)，암톨메틴구아실(amtolmetinguacil)，아나세트랍핍(anacetrapib)，아나글립틴(anagliptin)，아나그렐리드(anagrelide)，아나모렐린(anamorelin)，아나스트로졸(anastrozole)，안크로드(ancrod)，안드로겐(androgen)，안드로그라폴리드(andrographolide)，아네코르타브(anecortave)，아니둘라펀진(anidulafungin)，아니라세탐(aniracetam)，아니스트렙프랄스(anistreplase)，안로티닙(anlotinib)，안타졸린(antazoline)，안티안드로겐스(antiandrogens)，안티네오플라스톤 A-10(antineoplaston A-10)，안티네오플라스톤 AS2-1(antineoplaston AS2-1)，안토플록사신 하이드로클로라이드(antofloxacin hydrochloride)，안트로퀴노놀(antroquinonol)，아파베타론(apabetalone)，아팔루트아마이드(apalutamide)，아파티닙 메실레이트(apatinib mesylate)，아파지퀴온(apaziquone)，아필리모드 메실레이트(apilimod mesylate)，아픽사반(apixaban)，아포모르핀(apomorphine)，아포모르핀 하이드로클로라이드(apomorphine hydrochloride)，아프레밀라스트(apremilast)，아프레피탄트(aprepitant)，아프리시타빈(apricitabine)，아람콜(aramchol)，아라니디핀(aranidipine)，아라세르타코나졸(arasertaconazole)，아라세르타코나졸 에니트레이트(arasertaconazol enitrate)，아르바클로펜(arbaclofen)，아르바클로펜 플라카르빌(arbaclofen placarbil)，아르베카신(arbekacin)，아르베카신 설페이트(arbekacin sulfate)，아르데파린 소듐(ardeparin sodium)，아르포르모테롤(arformoterol)，아르가트로반(argatroban)，아르할로페네이트(arhalofenate)，아리모클로몰(arimoclomol)，아리피페라졸(aripiprazole)，아리피페라졸 라우록실(aripiprazole lauroxil)，아르모다피닐(armodafinil)，아르세닉트라이옥사이드(arsenictrioxide)，아르세니오산(arsenious acid)，아르테페노멜 메실레이트(artefenomel mesylate)，아르테메터(artemether)，아르테모틸(artemotil)，아르테니몰(artenimol)，아르테롤란 말레이트(arterolane maleate)，아르테수네이트(artesunate)，아르티스(Artiss)，아사피프란트(asapiprant)，아세나핀(asenapine)，아시마돌린(asimadoline)，아스토드리머(astodrimer)，아스트라갈로시드(astragaloside)，아수나프레비르(asunaprevir)，아타시구아트(ataciguat)，아타루렌(ataluren)，아타자나비르(atazanavir)，아타자나비르 설페이트(atazanavir sulfate)，아테놀올(atenolol)，아토목세틴(atomoxetine)，아토르바스타틴(atorvastatin)，아토르바스타틴 칼슘(atorvastatin calcium)，아토르바스타틴 스트론튬(atorvastatin strontium)，아토바퀴온(atovaquone)，아트라센탄(atrasentan)，아트로핀(atropine)，우라노핀(auranofin)，우리클로센(auriclosene)，아바신캡타드페골 소듐 (avacincaptadpegol sodium)，아바코판(avacopan)，아바나필(avanafil)，아바트롬보파그(avatrombopag)，아비박탐(avibactam)，아비박탐 소듐(avibactam sodium)，아비디녹스(AvidinOx)，아비프타딜(aviptadil)，아비티닙(avitinib)，아보랄스타트(avoralstat)，아젤로프란(axelopran)，아지티닙(axitinib)，아자시티딘(azacitidine)，아자시티딘(azacytidine)，아자세트론(azasetron)，아젤라산(azelaic acid)，아젤라스틴(azelastine)，아젤라스틴 하이드로클로라이드(azelastine hydrochloride)，아젤리라곤(azeliragon)，아젤니디핀(azelnidipine)，아질사르탄(azilsartan)，아질사르탄 메독소밀 포타슘(azilsartan medoxomil potassium)，아질사르탄 트라이메틸에탄올아민(azilsartan trimethylethanolamine)，아지밀리드(azimilide)，아지트로마이신(azithromycin)，아지트로마이신 락토비오네이트(azithromycin lactobionate)，아즈트레오남(aztreonam)，아즈트레오남 리신(aztreonam lysine)，아주부딘(azvudine)，바클로펜(baclofen)，바페티닙(bafetinib)，바이칼레인(Baicalein)，바이칼린(baicalin)，BAK-프리라타노프로스트(BAK-freelatanoprost)，발로프록사신(balofloxacin)，발살아자이드(balsalazide)，발살아자이드 소듐(balsalazide sodium)，밤부테롤(bambuterol)，바라세르티닙(barasertib)，바르독솔론 메틸(bardoxolone methyl)，바리시티닙(baricitinib)，바르니디핀(barnidipine)，바스미사닐(basmisanil)，바테펜테롤 숙시네이트(batefenterol succinate)，바제독시펜(bazedoxifene)，베클라부비르(beclabuvir)，베클로메타손 다이프로피오네이트(beclometasone dipropionate)，베다퀴린(bedaquiline)，베도르아드린(bedoradrine)，벨리노스타트(belinostat)，벨로라닙(beloranib)，벨로테칸(belotecan)，벰페도산(bempedoic acid)，베나페넴(benapenem)，베나제프릴(benazepril)，벤사이클로퀴듐 브로마이드(bencycloquidium bromide)，벤다무스틴(bendamustine)，벤다무스틴 하이드로클로라이드(bendamustine hydrochloride)，베니디핀(benidipine)，벤세르아자이드(benserazide)，벤타마피모드(bentamapimod)，벤잘코늄 클로라이드 (benzalkonium chloride)，벤즈하이드로코돈(benzhydrocodone)，벤즈니다졸(benznidazole)，벤조케인(benzocaine)，벤조일페록사이드(benzoylperoxide)，벤질다민HCL(benzydamineHCL)，베포타스틴(bepotastine)，베포타스틴 칼슘다이하이드레이트(bepotastine calciumdihydrate)，베포타스틴 살리실레이트(bepotastine salicylate)，베락탄트(beractant)，베라프로스트 소듐(beraprost sodium)，베실플록사신(besifloxacin)，베시포비르(besifovir)，베시피르딘(besipirdine)， 베타-엘레멘(beta-elemene)，베타히스틴(betahistine)，무수 베타인(betaine anhydrous)，베타메타손(betamethasone)，베타메타손 부티레이트 프로피오네이트(betamethasone butyrate propionate)，베타메타손 다이프로피오네이트(betamethasone dipropionate)，베타메타손 발레레이트(betamethasone valerate)，베타미프론(betamipron)，베탁솔롤(betaxolol)，벡탁솔롤 하이드로클로라이드(betaxolol hydrochloride)，베타네콜(bethanechol)，베트리자반(betrixaban)，베바시주맙(bevacizumab)，벡사글리플로진(bexagliflozin)，벡사로텐(bexarotene)，베자피브레이트(bezafibrate)，바이아펀진(biafungin)，바이아페넴(biapenem)，바이칼루트아마이드(bicalutamide)，바이시자르(bicizar)，빅테그라비르(bictegravir)，바이사이클올(bicyclol)，빌라스틴(bilastine)，바이마토프로스트(bimatoprost)，바이니메티닙(binimetinib)，바이오틴(biotin)，바이라브레시브다이하이드레이트(birabresibdihydrate)，비스칼시트레이트 포타슘(biskalcitrate potassium)，비수무스 서브갈레이트(bismuth subgallate)，비스무틸 에카베트(bismuthyl ecabet)，비스노르심세린(bisnorcymserine)，비소프롤올(bisoprolol)，비소프롤올 푸마레이트(bisoprolol fumarate)，바테스피라마이신(bitespiramycin)，바이살로머(bixalomer)，블레오마이신(bleomycin)，블로난세린(blonanserin)，보안마이신 하이드로클로라이드(boanmycin hydrochloride)，보세프레비르(boceprevir)，보르테조밉(bortezomib)，보센탄(bosentan)，보센탄 하이드레이트(bosentan hydrate)，보수티닙(bosutinib)，보박탄트(bovactant)，브렉피프라졸(brexpiprazole)，브리사이크리브 소듐(briciclib sodium)，브리가티닙(brigatinib)，브릴아시딘(brilacidin)，브리마피티드(brimapitide)，브라모니딘(brimonidine)，브린시도포비르(brincidofovir)，브린졸아마이드(brinzolamide)，브리바니발라니네이트(brivanibalaninate)，브리바라세탐(brivaracetam)，브리부딘(brivudine)，브로루시주맙(brolucizumab)，브로마제팜(bromazepam)，브로페낙(bromfenac)，브로페낙 소듐(bromfenac sodium)，브로모크립틴(bromocriptine)，브론초스타트(bronchostat)，브로티졸람(brotizolam)，브르요스타틴-1(bryostatin-1)，부신돌올(bucindolol)，부클라데신(bucladesine)，부데소니드(budesonide)，부디핀(budipine)，부플로메딜(buflomedil)，부라퀴인(bulaquin)，부나조신(bunazosin)，부파르리십(buparlisib)，부피斯케인(bupivacaine)，부피바케인 하이드로클로라이드(bupivacaine hydrochloride)，부프레노르핀(buprenorphine)，부프레노르핀 하이드로클로라이드(buprenorphine hydrochloride)，부프로피온(bupropion)，부프로피온 하이드로클로라이드(bupropion hydrochloride)，부리자포르(burixafor)，부세렐린 아세테이트(buserelin acetate)，부스피론(buspirone)，부스피론 하이드로클로라이드(buspirone hydrochloride)，부설판(busulfan)，부설펙스(busulfex)，부테나핀(butenafine)，부토르파놀 타르트레이트(butorphanol tartrate)，부틸프탈리드(butylphthalide)，카바지탁셀(cabazitaxel)，카베르골린(cabergoline)，카보테그라비르(cabotegravir)，카보잔티닙 S-말레이트(cabozantinib S-malate)，카다졸리드(cadazolid)，카드로프록사신(cadrofloxacin)，카페인(caffeine)，카페인 시트레이트(caffeine citrate)，카프네아(cafnea)，카푸세르팁 하이드로클로라이드(cafusertib hydrochloride)，칼시포트라이올(calcipotriol)，칼리트라이올(calcitriol)，아세트산 칼슘(calcium acetate)，칼슘폴리네이트(calciumfolinate)，칼슘 레보폴리네이트(calcium levofolinate)，칼슘 폴리카보필(calcium polycarbophil)，칼프악탄트(calfactant)，칼만가포디피르(calmangafodipir)，칼서프(calsurf)，카미시날(camicinal)，카모스타트 메실레이트(camostat mesylate)，캄프토테신(camptothecin)， 카나글리폴진 칸데사르탄(canagliflozin，candesartan)，칸데사르탄 실렉세틸(candesartan cilexetil)，칸포스프아마이드(canfosfamide)，칸그레로르(cangrelor)，칸나비디올(cannabidiol)，캐펙시타빈(capecitabine)，캡마티닙(capmatinib)，캡사이신(capsaicin)，캡토프릴(captopril)，카르바마제핀(carbamazepine)，카르베토신(carbetocin)，카르비도파(carbidopa)，카르비녹사민(carbinoxamine)，카보시스테인(cqsbocysteine)，카보플라틴(carboplatin)，카르디도파(cardidopa)，카르필조밉(carfilzomib)，카르글루미산(carglumicacid)，카리프라진(cariprazine)，카리스바메이트(carisbamate)，카르무스틴(carmustine)，카로테가스트메틸(carotegastmethyl)，카르테올롤(carteolol)，카르테올롤 하이드로클로라이드(carteolol hydrochloride)，카루모남(carumonam)，카르베딜올(carvedilol)，카르베딜올포스페이트(carvedilolphosphate)，카스포푸진(caspofungin)，카테친(catechin)，세브라노파돌(cebranopadol)，세디라닙(cediranib)，세파클로르(cefaclor)，세파드록실(cefadroxil)，세파티아미딘(cefathiamidine)，세파졸린 소듐 펜타하이드레이트(cefazolin sodium pentahydrate)，세프카펜(cefcapene)，세프디니르(cefdinir)，세프디토렌피복실(cefditorenpivoxil)，세프핌(cefepime)，세프핌 다이하이드로클로라이드(cefepime dihydrochloride)，세프타메트피복실 하이드로클로라이드(cefetametpivoxil hydrochloride)，세피데로콜(cefiderocol)，세필라반신(cefilavancin)，세프미녹스(cefminox)，세포페라존(cefoperazone)，세포페라존 소듐(cefoperazone sodium)，세포셀리스(cefoselis)，세포탁심(cefotaxime)，세포탁심 소듐(cefotaxime sodium)，세포티암 세포조프란(cefotiam，cefozopran)，세프피롬(cefpirome)，세프포독심(cefpodoxime)，세프프로질(cefprozil)，세프타롤린(ceftaroline)，세프타롤린 포사밀(ceftaroline fosamil)，세프타지딤(ceftazidime)，세프티부텐(ceftibuten)，세프토비프롤레 메도카릴(ceftobiprole medocaril)，세프토로잔 설페이트(ceftolozane sulfate)，세프트라이아존(ceftriaxone)，세프트라이아존 소듐(ceftriaxone sodium)，세푸록심(cefuroxime)，세푸록심 소듐(cefuroxime sodium)，셀레콕시브(celecoxib)，셀고시비르(celgosivir)，셀리프롤올(celiprolol)，셀프로텍트(cellprotect)，세네스틴(cenestin)，세니크리비록(cenicriviroc)，센사부딘(censavudine)，센타나파딘(centanafadine)，세팔로스포린(cephalosporin)，세라리피모드(ceralifimod)，세르둘라티닙(cerdulatinib)，세르티닙(ceritinib)，세리룸나이트레이트(ceriumnitrate)，세틸리스타트(cetilistat)，세트리진(cetirizine)，세트락세이트(cetraxate)，세비멜린(cevimeline)，체노데옥시콜린산(chenodeoxycholic acid)，콜시부타민(chlocibutamine)，클로르헥시딘(chlorhexidine)，클로르마디논 아세테이트(chlormadinone acetate)，클로로제닉산(chlorogenic acid)，클로로퀴인(chloroquine)，클로로옥소퀴놀린(chloroxoquinoline)，클로르페니르아민(chlorpheniramine)，클로르페니르아민 말레이트(chlorpheniramine maleate)，클로르페니르아민 폴리스티렉스(chlorpheniramine polistirex)，클로르탈리돈(chlortalidone)，콜레칼시페롤(cholecalciferol)，콜산(cholic acid)，콜린 알포스세레이트(choline alfoscerate)，콜린 다이에팔레스타트(choline diepalrestat)，콜린 페노피브레이트(choline fenofibrate)，시클레소니드(ciclesonide)，시클로피록솔아민(ciclopiroxolamine)，시클로스포린(ciclosporin)，시도포비르(cidofovir)，시도제핀(cidoxepin)，클리라스타틴(cilastatin)，클리라자프릴(cilazapril)，클리니디핀(cilnidipine)，실로스타졸(cilostazol)，시메티딘(cimetidine)，시나살세트(cinacalcet)，시넵아자이드 말레이트(cinepazide maleate)，신히알루로네이트 소듐(cinhyaluronate sodium)，시니타프리드 타르타레이트(cinitapride tartrate)，시파르가민(cipargamin)，시프로피브레이트(ciprofibrate)，시프로플록사신(ciprofloxacin)，시프로플록사신 하이드로클로라이드(ciprofloxacin hydrochloride)，시라파란태그(ciraparantag)，시르카딘(circadin)，시사크라쿠륨 베실레이트(cisatracurium besilate)，시스플라틴(cisplatin)，시탈로프람(citalopram)，시탈로프람 하이드로브로마이드(citalopram hydrobromide)，시티콜린(citicoline)，시트룰린(citrulline)，클라드리빈(cladribine)，클라리트로마이신(clarithromycin)，클라불라네이트 포타슘(clavulanate potassium)，클라부란산(clavulanic acid)，클라조센탄(clazosentan)，클레비디핀(clevidipine)，클레부딘(clevudine)，클린다마이신(clindamycin)，클린다마이신 하이드로클로라이드(clindamycin hydrochloride)，클린다마이신 포스페이트(clindamycin phosphate)，클리오퀴놀(clioquinol)，클로바잠(clobazam)，클로베타솔프로피오네이트(clobetasolpropionate)，클로베타솔프로피오네이트폼(clobetasolpropionatefoam)，클로드론산(clodronic acid)，클로파라빈(clofarabine)，클로파지민(clofazimine)，클로미프라민(clomipramine)，클로미프라민 하이드로클로라이드(clomipramine hydrochloride)，클로나제팜(clonazepam)，클로니딘(clonidine)，클로니딘 하이드로클로라이드(clonidine hydrochloride)，클로피도그렐(clopidogrel)，클로피도그렐 베실레이트(clopidogrel besylate)，클로피도그렐 바이설페이트(clopidogrel bisulfate)，클로디포그렐 캄실레이트(clopidogrel camsylate)，클로디포그렐 하이드로젠설페이트(clopidogrel hydrogensulfate)，클로디포그렐 나파디실레이트(clopidogrel napadisilate)，클로피도그렐 레시네이트(clopidogrel resinate)，클로트라이마졸(clotrimazole)，클로자핀(clozapine)，코밤아마이드(cobamamide)，코비시스타트(cobicistat)，코비메티닙(cobimetinib)，코비프로스톤(cobiprostone)，코데인(codeine)，코데인 폴리스티렉스(codeine polistirex)，콜치신(colchicine)，콜레칼시페롤(colecalciferol)，콜레세베람(colesevelam)，콜레스티란(colestilan)，콜포르신 다로페이트(colforsin daropate)，콜포세릴 팔미테이트(colfosceril palmitate)，콜리스티메테이트 소듐(colistimethate sodium)，코니밥탄(conivaptan)，코판리십(copanlisib)，코페히스티딘(copperhistidine)，코르텍솔론 17 알파-프로피오네이트(cortexolone 17 alpha-propionate)，코시테칸(cositecan)，크레놀라닙(crenolanib)，크리다니모드 소듐(cridanimod sodium)，크리사보롤(crisaborole)，크리조티닙(crizotinib)，크로펠레머(crofelemer)，크롤리불린(crolibulin)，크로모글릭산(cromoglicic acid)，크로몰린 소듐(cromolyn sodium)，쿠타메신 다이하이드로클로라이드(cutamesine dihydrochloride)，사이아노코발라민(cyanocobalamin)， 사이클리진 락테이트(cyclizine lactate)，사이클로벤자프린 하이드로클로라이드(cyclobenzaprine hydrochloride)，사이클로포스파미드(cyclophosphamide)，사이클로포스파미드 모노하이드레이트(cyclophosphamide monohydrate)，사이클로스포린(cyclosporin)，사이프로테론(cyproterone)，사이프로테론 아세테이트(cyproterone acetate)，시스타라빈(cytarabine)，시스타라빈 옥포스페이트(cytarabine ocfosfate)，다비가트란 에텍실레이트(dabigatran etexilate)，다브라페닙(dabrafenib)，다클라타스비르(daclatasvir)，다코미티닙(dacomitinib)，달바반신(dalbavancin)，달세트라피브(dalcetrapib)，달팜프리딘(dalfampridine)，달포프리스틴(dalfopristin)，달테파린 소듐(dalteparin sodium)，다나파로이드 소듐(danaparoid sodium)，다나졸(danazol)，다니리신(danirixin)，다노프레비르(danoprevir)，단트롤렌 소듐(dantrolene sodium)，다누세르팁(danusertib)，다파코나졸(dapaconazole)，다파글리플로진(dapagliflozin)，다파글리플로진 프로페인다이올(dapagliflozin propanediol)，다이피프라졸(dapiprazole)，다피비린(dapivirine)，다포세틴(dapoxetine)，다프로두스타트(daprodustat)，답손(dapsone)，다리페나신(darifenacin)，다리나파르신(darinaparsin)，다루나비르(darunavir)，다사부비르(dasabuvir)，다사티닙(dasatinib)，다소트릴린(dasotraline)，다우노루비신(daunorubicin)，데시타빈(decitabine)，데쿠프레이트(decuprate)，데팍티닙(defactinib)，데페라시록스(deferasirox)，데페리프론(deferiprone)，데페록사민 메실레이트(deferoxamine mesylate)，델플라자코르트(deflazacort)，데플렉시폴(deflexifol)，델라플록사신(delafloxacin)，델라마니드(delamanid)，델라프릴(delapril)，델라프릴 하이드로클로라이드(delapril hydrochloride)，델라비르딘(delavirdine)，데니불린(denibulin)，데옥시안드로그라폴리드(deoxyandrographolide)，데르마탄설페이트(dermatansulfate)，데스플루레인(desflurane)，데시프르아민 하이드로클로라이드(desipramine hydrochloride)，데슬로라타딘(desloratadine)，데스모프레신(desmopressin)，데스모프레신 아세테이트(desmopressin acetate)，데소게스트렐(desogestrel)，데소니드(desonide)，데스벤라팍신(desvenlafaxine)，듀덱스트로메토르판 하이드로브로마이드(deudextromethorphan hydrobromide)，듀테포르핀(deuteporfin)，듀테레이트 레보도파(deuterated levodopa)，듀테라테드벤라팍신(deuteratedvenlafaxine)，듀테트라베나진(deutetrabenazine)，덱사메타손(dexamethasone)，덱사메타손 아세테이트(dexamethasone acetate)，덱사메타손 시페실레이트(dexamethasone cipecilate)，덱사메타손 팔미테이트(dexamethasone palmitate)，덱사메타손 소듐포스페이트(dexamethasone sodiumphosphate)，덱스암페타민(dexamfetamine)，덱사나비놀(dexanabinol)，덱스퍼룸(dexferrum)，덱스케토프로펜 트로모메타몰(dexketoprofen trometamol)，덱스란소프라졸(dexlansoprazole)，덱스메데토미딘(dexmedetomidine)，덱스메틸페니데이트(dexmethylphenidate)，덱스프라미펙솔(dexpramipexole)，덱스라조세인(dexrazoxane)，덱스소탈올(dexsotalol)，덱스트로암페타민 사카레이트(dextroamphetamine saccharate)，덱스트로암페타민 설페이트(dextroamphetamine sulfate)，덱스트로메토르판(dextromethorphan)，텍스트로메토르판 하이드로브로마이드(dextromethorphan hydrobromide)，덱스트로프로폭시펜(dextropropoxyphene)，다이아세레인(diacerein)，다이아모르핀 하이드로클로라이드(diamorphine hydrochloride)，다이안하이드로갈락티톨(dianhydrogalactitol)，다이아제팜(diazepam)，다이아조옥시데콜린(diazoxidecholine)，다이클로페낙(diclofenac)，다이클로페낙 칼슘(diclofenac potassium)，다이클로페낙 소듐(diclofenac sodium)，다이클로펜아마이드(diclofenamide)，다이사이클로플라틴(dicycloplatin)，다이다노신(didanosine)，다이에노게스트(dienogest)，다이플루프레드네이트(difluprednate)，다이옥신(digoxin)，다이호모감마-리놀레산(dihomogamma-linolenic acid)，다이하이드로에르고크리스틴(dihydroergocristine)，다이하이드로에르고타민(dihydroergotamine)，다이하이드로에르로타민 메실레이트(dihydroergotamine mesylate)， 딜티아젬(diltiazem)，딜티아젬 하이드로클로라이드(diltiazem hydrochloride)，다이메스나(dimesna)，다이메틸 푸마레이트(dimethyl fumarate)，다이미르아세탐(dimiracetam)，다이노프로스톤(dinoprostone)，다이페닐사이클로프로페논(diphenylcyclopropenone)，다이프라글루란트(dipraglurant)，다이피리다몰(dipyridamole)，다이쿠아포솔테트라 소듐(diquafosoltetra sodium)，다이리트로마이신(dirithromycin)，다이설펜톤 소듐(disufenton sodium)，다이설피람(disulfiram)，다이트라놀(dithranol)，d-메타돈(d-methadone)，도카르프아민(docarpamine)，도세탁셀(docetaxel)，도시파르스타트(dociparstat)，도코사놀(docosanol)，도페틸리드(dofetilide)，돌라세트론(dolasetron)，돌루테그라비르(dolutegravir)，돔페리돈(domperidone)，도나페닙 토실레이트(donafenib tosylate)，도네페질(donepezil)，도네페질 하이드로클로라이드(donepezil hydrochloride)，도파민(dopamine)，도라비린(doravirine)，도리페넴(doripenem)，도르졸아마이드(dorzolamide)，도르졸아마이드 하이드로클로라이드 (dorzolamide hydrochloride)，도스말페이트(dosmalfate)，독사쿠리움 클로라이드(doxacurium chloride)，독사조신(doxazosin)，독사조신 메실레이트(doxazosin mesylate)，독세핀 하이드로클로라이드(doxepin hydrochloride)，독세르칼시페롤(doxercalciferol)，독시플루리딘(doxifluridine)，독소필린(doxofylline)，독소루비신(doxorubicin)，독소루비신 하이드로클로라이드(doxorubicin hydrochloride)，독시사이클린(doxycycline)，독시사이클린 하이클레이트(doxycycline hyclate)，독실아민 숙시네이트(doxylamine succinate)，드로나비놀(dronabinol)，드로네다론(dronedarone)，드로스피레논(drospirenone)，다록시도파(droxidopa)，D-타가토오스(D-tagatose)，둘옥세틴(duloxetine)，둘옥세틴 하이드로클로라이드(duloxetine hydrochloride)，투타스테리드(dutasteride)，두벨리십(duvelisib)，에바스틴(ebastine)，에베르코나졸(eberconazole)，엡셀렌(ebselen)，에카베트(ecabet)，에코나졸렌나이트레이트(econazolenitrate)，에코피팜(ecopipam)，에다라본(edaravone)，에디복세틴(edivoxetine)，에도네르픽 말레이트(edonerpic maleate)，에독사반(edoxaban)，에파투타존(efatutazone)，에파비렌즈(efavirenz)，에피나코나졸(efinaconazole)，엘플로르니틴(eflornithine)，에포니디핀 하이드로클로라이드(efonidipin hydrochloride)，에구알렌 소듐(egualen sodium)，에코사펜타노산 모노글리세리드(eicosapentaenoic acid monoglycerides)，엘파피브라노르(elafibranor)，엘라골릭스(elagolix)，엘라미프레티드(elamipretide)，엘바스비르(elbasvir)，엘데칼시톨(eldecalcitol)，엘레클라진(eleclazine)，엘레스클로몰 소듐(elesclomol sodium)，엘레트립판(eletriptan)，엘리글루스타타르트레이트(eliglustattartrate)，엘로빅시바트(elobixibat)，엘트롬보파그(eltrombopag)，엘룩사돌린 다이하이드로클로라이드(eluxadoline dihydrochloride)，에비테그라비르(elvitegravir)，엠도가인(emdogain)，에메다스틴(emedastine)，에메르아마이드(emeramide)，에믹수스타트(emixustat)，에모뎁시드(emodepside)，엠파글리플로진(empagliflozin)，엠리카산(emricasan)，엠트리시타빈(emtricitabine)，에날라프릴(enalapril)，에날라프릴말레이트(enalaprilmaleate)，에나시데닙(enasidenib)，엔세니클린(encenicline)，엔클로미펜 시트레이트(enclomifene citrate)，에코라페닙(encorafenib)，엔독시펜(endoxifen)，엔보사름(enobosarm)，에녹사신 글루코네이트(enoxacin gluconate)，에녹사신 소듐(enoxaparin sodium)，엔프로스틸(enprostil)，엔타카폰(entacapone)，엔타소불린(entasobulin)，엔테카비르(entecavir)，엔테카비르 말레이트(entecavir maleate)，엔티노스타트(entinostat)，엔토스플레티닙(entospletinib)，엔트렉티닙(entrectinib)，엔잘루트아마이드(enzalutamide)，엔자스타우린(enzastaurin)，에파카도스타트(epacadostat)，에팔레스타트(epalrestat)，에페리손(eperisone)，에페트라보롤(epetraborole)，에페드린 설페이트(ephedrine sulfate)，에피나스틴 하이드로클로라이드(epinastine hydrochloride)，에피네프린(epinephrine)，에피루비신(epirubicin)，에피루비신 하이드로클로라이드(epirubicin hydrochloride)，에피살반(episalvan)，에피티닙(epitinib)，에플레레논(eplerenone)，에포프로스테놀(epoprostenol)，에프리스테리드(epristeride)，에프로다이세이트(eprodisate)，에프로사르탄(eprosartan)，엡타플라틴(eptaplatin)，에라바사이클린(eravacycline)，에르다피티닙(erdafitinib)，에르도스테인(erdosteine)，에리불린 메실레이트(eribulin mesylate)，에르로티닙(erlotinib)，에르타페넴(ertapenem)，에르테베렐(erteberel)，에르투글리플로진(ertugliflozin)，에리쓰로마이신(erythromycin)，에리쓰로마이신 아시스트레이트(erythromycin acistrate)，에리쓰로마이신 스티노프레이트(erythromycin stinoprate)，에스시탈로프람(escitalopram)，에스케타민(esketamine)，에스케타민 하이드로클로라이드(esketamine hydrochloride)，에실리카르바제핀 아세테이트(eslicarbazepine acetate)，에스몰올 하이드로클로라이드(esmolol hydrochloride)，에소메프라졸(esomeprazole)，에소메프라졸 마그네슘(esomeprazole magnesium)，에소메프라졸 스트론튬(esomeprazole strontium)，에소메프라졸(esomeprazole)，에스테트롤(estetrol)，에스트라다이올(estradiol)，에스트라다이올 아세테이트(estradiol acetate)，에스트라다이올 사이피오네이트(estradiol cypionate)，에스트라다이올 발레레이트(estradiol valerate)，에스트라다이올(estrodiol)，에스트로겐(estrogen)，에수베라프로스트 소듐(esuberaprost sodium)，에스조피클론(eszopiclone)，에타미카스타트(etamicastat)，에트암부톨 하이드로클로라이드(ethambutol hydrochloride)，에타셀렌(ethaselen)，에티닐에스트라다이올(ethinylestradiol)，에틸하이드로젠푸마레이트 칼슘(ethylhydrogenfumarate calcium)，에틸하이드로젠푸마레이트 마그네슘(ethylhydrogenfumarate magnesium)，에틸하이드로젠푸마라 테징크(ethylhydrogenfumara tezinc)，에티닐에스트라다이올(ethynylestradiol)，에티드론산(etidronic acid)，에티마이신 설페이트(etimicin sulfate)，에티리노테칸페골(etirinotecanpegol)，에티졸람(etizolam)，에토돌락(etodolac)，에토노게스트렐(etonogestrel)，에토포시드(etoposide)，에토포시드 포스페이트(etoposide phosphate)，에토리콕시브(etoricoxib)，에트라비린(etravirine)，에트리파밀(etripamil)，에우파틸린(eupatilin)，에벤아마이드 하이드로클로라이드(evenamide hydrochloride)，에베롤리무스(everolimus)，에포포스프아마이드(evofosfamide)，에보글립틴(evogliptin)，엑세메스테인(exemestane)，엑센딘(9-39)(exendin(9-39))，엑센포르피늄 클로라이드(exeporfinium chloride)，에자티오스타트(ezatiostat)，에제티미베(ezetimibe)，에주트로미드(ezutromid)，파돌미딘(fadolmidine)，파드로졸(fadrozole)，팔다프레비르(faldaprevir)，팔레칼시트라이올(falecalcitriol)，팜시클로비르(famciclovir)，파미트닙(famitinib)，파모티딘(famotidine)，핌프리딘(fampridine)，파로페넴(faropenem)，파시티반트 클로라이드(fasitibant chloride)，파소르아세탐(fasoracetam)，파수딜(fasudil)，파수딜 하이드로클로라이드(fasudil hydrochloride)，파수딜 메실레이트(fasudil mesylate)，파비피라비르(favipiravir)，페바르바메이트(febarbamate)，페북소스타트(febuxostat)，페도바파곤(fedovapagon)，펠바메이트(felbamate)，펠비낙 트로메타몰(felbinac trometamol)，펠로디핀(felodipine)，페미트라(femitra)，펜플루르아민 하이드로클로라이드(fenfluramine hydrochloride)，페노밤(fenobam)，페노피브레이트(fenofibrate)，페노피브르산(fenofibric acid)，페놀도팜(fenoldopam)，페노테롤(fenoterol)，펜레티니드(fenretinide)，펜탄일(fentanyl)，펜탄일 시트레이트(fentanyl citrate)，펜티코나졸(fenticonazole)，페르마게이트(fermagate)，페리시트레이트(ferriccitrate)，페리시말톨(ferricmaltol)，페루목시톨(ferumoxytol)，페소테로딘 푸마레이트(fesoterodine fumarate)，페비피프란트(fevipiprant)，펙시니다졸(fexinidazole)，펙소페나딘(fexofenadine)，피브린실란트(fibrinsealant)，피브리노겐(fibrinogen)，피브리노겐실란트(fibrinogensealant)，피닥소미신(fidaxomicin)，필라네십(filanesib)，필고티닙(filgotinib)，필로사이클로비르(filociclovir)，피마포르핀(fimaporfin)，피마사르탄(fimasartan)，피나플록사신(finafloxacin)，피나플록사신 하이드로클로라이드(finafloxacin hydrochloride)，피나스테리드(finasteride)，피네레논(finerenone)，핀골리모드(fingolimod)，피파메졸(fipamezole)，피르테칸페골(firtecanpegol)，플레카이니드(flecainide)，플레록사신(fleroxacin)，플리반세린(flibanserin)，플로목세프(flomoxef)，플록스우리딘(floxuridine)，플루아졸레팔리(fluazolepali)，플루코나졸(fluconazole)，플루다라빈(fludarabine)，플루마티닙(flumatinib)，플루마제닐(flumazenil)，플루니솔리드(flunisolide)，플루코시놀론 아세토니드(fluocinolone acetonide)，플루오시노니드(fluocinonide)，플루오라파신(fluorapacin)，플루오로우라실(fluorouracil)，플루옥세틴(fluoxetine)，플루옥세틴 하이드로클로라이드(fluoxetine hydrochloride)，플루피르틴(flupirtine)，플루르바이프로펜(flurbiprofen), 플루르바이프로페나세틸(flurbiprofenaxetil)，플루르바이프로펜 소듐(flurbiprofen sodium)，플루리트로마이신(flurithromycin)，플루티카손(fluticasone)，플루티카손 플루오레이트(fluticasone furoate)，플루티카손 프로피오네이트(fluticasone propionate)，플루트라이마졸(flutrimazole)，플루바스타틴(fluvastatin)，플루복사민(fluvoxamine)，폴산(folic acid)，폴리네이트(folinate)，폴리움깅코(foliumginkgo)，포메피졸(fomepizole)，포나델파르(fonadelpar)，폰다파리눅스 소듐(fondaparinux sodium)，포레티닙(foretinib)，포르메스테인(formestane)，포르모테롤(formoterol)，포르모테롤 푸마레이트(formoterol fumarate)，포로데신(forodesine)，포삼프레나비르(fosamprenavir)，포사프레피탄트(fosaprepitant)，포스브레타불린(fosbretabulin)，포스브레타불린 다이소듐(fosbretabulin disodium)，포스플로코나졸(fosfluconazole)，포스포마이신(fosfomycin)，포스포마이신 다이소듐(fosfomycin disodium)，포스포마이신트로메타몰(fosfomycintrometamol)，포시노프릴(fosinopril)，포시노프릴 소듐(fosinopril sodium)，포스미도마이신(fosmidomycin)，포스페니토인(fosphenytoin)，포스프로포폴(fospropofol)，포스라부코나졸(fosravuconazole)，포스타마티닙(fostamatinib)，포스템사비르 트로메타민(fostemsavir tromethamine)，포타글립틴 벤조에이트(fotagliptin benzoate)，포테무스틴(fotemustine)，프로바트립탄(frovatriptan)，프루퀸티닙(fruquintinib)，프도스테인(fudosteine)，플베스트란트(fulvestrant)，푸나피드(funapide)，푸로세미드(furosemide)，푸시드산(fusidic acid)，가바펜틴(gabapentin)，카바펜틴에나카르빌(gabapentinenacarbil)，가벡세이트 메실레이트(gabexate mesylate)，가사이클리딘(gacyclidine)，가도부트롤(gadobutrol)，가도베르세트아마이드(gadoversetamide)，가도세테이트 다이소듐(gadoxetate disodium)，갈란트아민(galantamine)，갈레테론(galeterone)，갈리데스비르(galidesivir)，질산 갈륨(gallium nitrate)，갈루니세르티닙(galunisertib)，감보그산(gambogic acid)，가낙솔론(ganaxolone)，간사이클로비르(ganciclovir)，가네테스핍(ganetespib)，가니렐릭스 아세테이트(ganirelix acetate)，가레녹사신(garenoxacin)，가티플록사신(gatifloxacin)，가티플록사신 메실레이트(gatifloxacin mesylate)，게다톨리십(gedatolisib)，게피티닙(gefitinib)，젬카빈(gemcabene)，젬시타빈(gemcitabine)，젬시타빈 하이드로클로라이드(gemcitabine hydrochloride)，젬피브로질(gemfibrozil)，젬피플록사신(gemifloxacin)，젬미글립틴(gemigliptin)，젬미글립틴타르타르산(gemigliptintartaric acid)，제니스테인(genistein)，젠타미신(gentamicin)，젠티오피크린(gentiopicrin)，게피론(gepirone)，게포티다신(gepotidacin)，게스토덴(gestodene)，게스트리논(gestrinone)，티몰올 말레이트(timolol maleate)，길테리티닙(gilteritinib)，짐머라실(gimeracil)，진세노시드C-K(ginsenosideC-K)，진세노시드Rg3(ginsenosideRg3)，기비노스타트(givinostat)，글라스데깁(glasdegib)，글라티라머 아세테이트(glatiramer acetate)，글레카프레비르(glecaprevir)，글레사티닙 글리콜레이트(glesatinib glycolate)，글리벤클아마이드(glibenclamide)，글리클아자이드(gliclazide)，글리메피리드(glimepiride)，글리피지드(glipizide)，글루포스프아마이드(glufosfamide)，글루타민(glutamine)，글루타티오나르센옥사이드(glutathionarsenoxide)，글리세롤 페닐부티레이트(glycerol phenylbutyrate)，글리코피로니움(glycopyrronium)，글리코피로니움 브로마이드(glycopyrronium bromide)，글리코피로니움 토실레이트(glycopyrronium tosylate)，글리사이르히지산(glycyrrhizic acid)，갱글리오시드(ganglioside)，골로티모드(golotimod)，고소글립틴(gosogliptin)，그라니세트론(granisetron)，그라니세트론 하이드로클로라이드(granisetron hydrochloride)，그라조프레비르(grazoprevir)，구아이페네신(guaifenesin)，구아이메살(guaimesal)，구안파신(guanfacine)，거스페리무스 트라이하이드로클로라이드(gusperimus trihydrochloride)，해모필루스인플루엔자(haemophilusinfluenzae)，할로베타솔 프로피오네이트(halobetasol propionate)，할로판트린(halofantrine)，할로메타손(halometasone)，힐론(healon)，헤마토포르피린(hematoporphyrin)，헤메아르기네이트(hemearginate)，헤모코아구라스 아쿠투스(hemocoagulase acutus)，헤파린(heparin)，헤르비론(Herbiron)，헤트롬보파그(hetrombopag)，헥스텐드(hextend)，히겐아민하이드로클로라이드(higenaminehydrochloride)，히스타민 다이하이드로클로라이드(histamine dihydrochloride)，HPPH광감제(HPPHphotosensitizer)，휴먼아포트랜스페린(humanapotransferrin)，휴먼플라스미노겐(humanplasminogen)，휴페르진A(huperzineA)，히알루로네이트 소듐(hyaluronate sodium)，하이드랄라진(hydralazine)，하이드로클로라이드(hydrochloride)，하이드로클로로티아지드(hydrochlorothiazide)，하이드로코돈(hydrocodone)，하이드로코돈 바이타르트레이트(hydrocodone bitartrate)，하이드로코돈 폴리스티렉스(hydrocodone polistirex)，하이드로코르티손(hydrocortisone)，과산화수소(hydrogenperoxide)，하이드로모르폰(hydromorphone)，하이드로모르폰 하이드로클로라이드(hydromorphone hydrochloride)，하이드로옥소코발라민(hydroxocobalamin)，하이드로옥시카바미드(hydroxycarbamide)，하이드록시클로로퀴인(hydroxychloroquine)，하이드록시프로게스테론 카프로에이트(hydroxyprogesterone caproate)，하이드록시사플오르 옐로우 A(hydroxysafflor yellowA)，하일라스탄(hylastan)，하이퍼리신(hypericin)，하이포에스톡시드(hypoestoxide)，이반드로네이트(ibandronate)，이반드론산(ibandronic acid)，이베로가스트N(iberogastN)，이보두탄트(ibodutant)，이부르티닙(ibrutinib)，이부딜라스트(ibudilast)，이부프로펜(ibuprofen)，이부틸리드(ibutilide)，이부틸리드 푸마레이트(ibutilide fumarate)，이카리틴(icaritin)，이클라프림(iclaprim)，이코사부테이트(icosabutate)，이코사펜트(icosapent)，이코사펜트에틸(icosapentethyl)，이코사펜트에틸에스터(icosapentethylester)，이코티닙 하이드로클로라이드(icotinib hydrochloride)，이달로피르딘(idalopirdine)，이다사누틀린(idasanutlin)，이데베논(idebenone)，이델라리십(idelalisib)，이독스우리딘(idoxuridine)，이드로녹실(idronoxil)，이페트로반(ifetroban)，이페트로반소듐(ifetrobansodium)，이구라티모드(iguratimod)，일란소프라졸(ilansoprazole)，일라프라졸(ilaprazole)，일로페리돈(iloperidone)，일로프로스트(iloprost)，일로프로스트베타덱스클라트레이트(iloprostbetadexclathrate)，이마티닙(imatinib)，이마티닙메실레이트(imatinibmesylate)，이메글리민(imeglimin)，이미다페나신(imidafenacin)，이미다프릴(imidapril)，이미다졸 살리실레이트(imidazole salicylate)，이미돌 하이드로클로라이드(imidol hydrochloride)，이미글립틴 다이하이드로클로라이드(imigliptin dihydrochloride)，이미페넴(imipenem)，이미퀴모드(imiquimod)，이미소파셈 망간(imisopasem manganese)，임레콕시브(imrecoxib)，인카드론산(incadronic acid)，인코보툴리눔톡신(incobotulinumtoxin)，인다카테롤(indacaterol)，인다카테롤 말레이트(indacaterol maleate)，인다프아마이드(indapamide)，인델옥사진(indeloxazine)，인디미테칸(Indimitecan)，인디나비르(indinavir)，인디세트론(indisetron)，인도메타신(indometacin)，인도라민(indoramin)，인도테칸(indotecan)，인독시모드(indoximod)，이네칼시톨(inecalcitol)，인피그라티닙(infigratinib)，인가비린(Ingavirin)，인게놀메부테이트(ingenolmebutate)，흡입 질산 나트륨(inhaled sodium nitrite)，페릭 카복시말토오스(ferric carboxymaltose)，이노신(inosine)，인테피르딘(intepirdine)，아이오디코나졸(iodiconazole)，이파타세르팁 다이하이드로클로라이드(ipatasertib dihydrochloride)，이프라글리플로진(ipragliflozin)，이프라트로피움(ipratropium)，이프라트로피움 브로마이드(ipratropium bromide)，이프타칼림(iptakalim)，이르베사르탄(irbesartan)，이리노테칸(irinotecan)，이리노테칸 하이드로클로라이드(irinotecan hydrochloride)，이리노테칸 수크로소페이트(irinotecan sucrosofate)，이로플벤(irofulven)，철 아이소말토시드1000(iron isomaltoside1000)，철 단백질 숙시닐레이트(iron protein succinylate)，이로수스타트(irosustat)， 이르소글라딘 말레이트(irsogladine maleate)，이사부코나조늄 클로라이드/설페이트(isavuconazonium chloride/sulfate)，아이소디부트(isodibut)，아이소플루레인(isoflurane)，아이소니아지드(isoniazid)，아이소프로필우노프로스톤(isopropylunoprostone)，아이소소르비드 다이나이트레이트(isosorbide dinitrate)，아이소소르비드 모노나이트레이트(isosorbide mononitrate)，아이소스테비올(isosteviol)，아이소티아플루딘(isothiafludine)，아이소트레티노인(isotretinoin)，이스라디핀(isradipine)，이스타록심(istaroxime)，이스트라데필린(istradefylline)，이타시티닙(itacitinib)，이토프리드 하이드로클로라이드(itopride hydrochloride)，이트라코나졸(itraconazole)，이바브라딘 헤미설페이트(ivabradine hemisulfate)，이바브라딘 하이드로클로라이드(ivabradine hydrochloride)，이바카프토르(ivacaftor)，이베르멕틴(ivermectin)，이보시데닙(ivosidenib)，아플리베르셉트(aflibercept)，익사베필론(ixabepilone)，익사조밉 시트레이트(ixazomib citrate)，칼리크레인(kallikrein)，강베이드(kangbeide)，케타민(ketamine)，케탄세린(ketanserin)，케토코나졸(ketoconazole)，케토프로펜(ketoprofen)，케토로락(ketorolac)，케토로락 트로메타민(ketorolac tromethamine)，케토티펜(ketotifen)，케베트린(kevetrin)，쿠코아민B 메실레이트(kukoamine Bmesylate)，L-4-클로로키누레닌(L-4-chlorokynurenine)，락시디핀(lacidipine)，라코스아마이드(lacosamide)，락티톨(lactitol)，라다리신(ladarixin)，라도스티길(ladostigil)，라플루니무스(laflunimus)，라푸티딘(lafutidine)，라미부딘(lamivudine)，라모트리긴(lamotrigine)，란디올올(landiolol)，란디올올 하이드로클로라이드(landiolol hydrochloride)，라니나미비르 옥타노에이트(laninamivir octanoate)，라노코나졸(lanoconazole)，란소프라졸(lansoprazole)，란타눔 카보네이트(lanthanum carbonate)，라파티닙(lapatinib)，라퀴니모드(laquinimod)，라로무스틴(laromustine)，라스미디탄(lasmiditan)，라소폭시펜(lasofoxifene)，라탄노프로스트(latanoprost)，라타노프로스테네부노드(latanoprostenebunod)，라우플루미드(lauflumide)，레디파스비르(ledipasvir)，레파물린(lefamulin)，레플루노미드(leflunomide)，렘보렉산트(lemborexant)，레날리도미드(lenalidomide)，렌티난(lentinan)，렌티난설페이트(lentinansulfate)，렌티난바이랄(lentinanviral)，렌바티닙 메실레이트(lenvatinib mesylate)，레르카니디핀(lercanidipine)，레시누라드(lesinurad)，레테프리눔(leteprinim)，레테르모비르(letermovir)，레트로졸(letrozole), 류신(leucine)，레우프로렐린 아세테이트(leuprorelin acetate)，레발부테롤(levalbuterol)，레발부테롤 하이드로클로라이드(levalbuterol hydrochloride)，레바미솔(levamisole)，레밤로디핀(levamlodipine)，레밤로디핀 베실레이트(levamlodipine besylate)，레밤로디핀 말레이트(levamlodipine maleate)，레베티라세탐(levetiracetam)，레보부피바케인(levobupivacaine)，레보카바스틴(levocabastine)，레보카비스틴 하이드로클로라이드(levocabastine hydrochloride)，레보카르니틴(levocarnitine)，레보세티리진 다이하이드로클로라이드(levocetirizine dihydrochloride)，레보도파(levodopa)，레보독사조신 메실레이트(levodoxazosin mesylate)，레보플록사신(levofloxacin)，레보케토코나졸(levoketoconazole)，레보밀나시프란(levomilnacipran)，레보나다이플록사신 아르기닌염(levonadifloxacin arginine salt)，레보노르게스트렐(levonorgestrel)，레보노르게스트렐 부타노에이트(levonorgestrel butanoate)，레보-펜사이노네이트 하이드로클로라이드(levo-phencynonate hydrochloride)，레보르니다졸(levornidazole)，레보르파놀(levorphanol)，레보시멘단(levosimendan)，레보티록신 소듐(levothyroxine sodium)，레보투스(levotuss)，L-글루타민(L-glutamine)，리도케인(lidocaine)，리피테그라스트(lifitegrast)，리구스트라진 하이드로클로라이드(ligustrazine hydrochloride)，리마프로스트(limaprost)，리나글립틴(linagliptin)，리네졸리드(linezolid)，리오티로닌(liothyronine)，리오티로닌 소듐(liothyronine sodium)，리포빈(lipobean)，리포소말 커큐민(liposomal curcumin)，리포테이초산(lipoteichoic acid)，리라나프테이트(liranaftate)，리스덱삼페타민(lisdexamfetamine)，리시노프릴(lisinopril)，리소필린(lisofylline)，리수리데하이드로젠 말레이트(lisuridehydrogen maleate)，리튬시트레이트(lithiumcitrate)，리튬숙시네이트(lithiumsuccinate)，리시밥탄(lixivaptan)，로바플라틴(lobaplatin)，로베글리타존(lobeglitazone)，로데나필 카보네이트(lodenafil carbonate)，로펙시딘(lofexidine)，로메플록사신(lomefloxacin)，로메리진(lomerizine)，로메리진 다이하이드로클로라이드(lomerizine dihydrochloride)，로미타피드(lomitapide)，로나파르닙(lonafarnib)，로니다민(lonidamine)，로페라미드(loperamide)，로페라미드옥사이드(loperamideoxide)，로피나비르(lopinavir)，로라타딘(loratadine)，로라제팜(lorazepam)，로르카세린(lorcaserin)，로레디플론(lorediplon)，로르라티닙(lorlatinib)，L-오르니틴L-아스파르테이트(L-ornithineL-aspartate)，로르녹시캄(lornoxicam)，로사르탄(losartan)，로사르탄 포타슘(losartan potassium)，로스마피모드(losmapimod)，로테프레드놀에타보네이트(loteprednoletabonate)，로바스타틴(lovastatin)，록사핀(loxapine)，록소프로펜(loxoprofen)，L-프라지쿠안텔(L-praziquantel)，루비프로스톤(lubiprostone)，루칸톤(lucanthone), 루세라스타트(lucerastat)，루시낙탄트(lucinactant)，루시타닙 하이드로클로라이드(lucitanib hydrochloride)，루시코나졸(luliconazole)，루마카프토르(lumacaftor)，루마테페론 톨루엔 설포네이트(lumateperone toluene sulfonate)，루메판트린(lumefantrine)，루미라콕시브(lumiracoxib)，루나칼시폴(lunacalcipol)，루라시돈(lurasidone)，루비넥테딘(lurbinectedin)，루세오글리플로진 하이드레이트(luseogliflozin hydrate)，루수트롬보파그(lusutrombopag)，리신 아세틸살리실레이트(lysine acetylsalicylate)，마시모렐린(macimorelin)，마시텐탄(macitentan)，마페니드(mafenide)，탄산 마그네슘(magnesium carbonate)，마그네슘 아이소글리시르히지네이트(magnesium isoglycyrrhizinate)，만가포디피르(mangafodipir)，만니디핀(manidipine)，만니디핀 다이하이드로클로라이드(manidipine dihydrochloride)，만니톨(mannitol)，마라비록(maraviroc)，마리바비르(maribavir)，마리조밉(marizomib)，마실루카스트(masilukast)，마시티닙(masitinib)，마보그루란트(mavoglurant)，막사칼시톨(maxacalcitol)，메벤다졸(mebendazole)，메비폰(mebiphon)，메카밀아민(mecamylamine)，메카밀아민 하이드로클로라이드(mecamylamine hydrochloride)，메클로에타민(mechlorethamine)，메코발라민(mecobalamin)，메드록시프로게스테론(medroxyprogesterone)，메드록시프로게스테론아세테이트(medroxyprogesteroneacetate)，메플로퀴인(mefloquine)，메게스트롤(megestrol)，메게스트롤아세테이트(megestrolacetate)，메이수오술리(meisuoshuli)，멜레보도파(m?levodopa)，멜록시캄(meloxicam)，멜팔란(melphalan)，멜팔란플루펜아마이드 하이드로클로라이드(melphalanflufenamide hydrochloride)，메만틴(memantine)，메만틴 하이드로클로라이드(memantine hydrochloride)，메나디온 소듐 바이설파이트(menadione sodium bisulfite)，메나테트레논(menatetrenone)，메파크린(mepacrine)，메퀴놀(mequinol)，머캅타민(mercaptamine)，머캅타민 바이타르트레이트(mercaptamine bitartrate)，머캅타민 하이드로클로라이드(mercaptamine hydrochloride)，머캅토퓨린(mercaptopurine)，메레스티닙(merestinib)，메로페넴(meropenem)，메로토신(merotocin)，메살아민(mesalamine)，메살라진(mesalazine)，메타카비르(metacavir)，메타독신(metadoxine)，메타미졸소듐(metamizolesodium)，메탁솔론(metaxalone)，메테르골린(metergoline)，메트포르민(metformin)，메트포르민 하이드로클로라이드(metformin hydrochloride)，메타돈(methadone)，메타졸아마이드(methazolamide)，메토트렉세이트(methotrexate)，메톡시플루란(methoxyflurane)，메틸아미노레불리네이트 하이드로클로라이드(methylaminolevulinate hydrochloride)，메틸날트렉손 브로마이드(methylnaltrexone bromide)，메틸날트렉손(methylnaltrexone)，메틸페니데이트(methylphenidate)，메틸페니데이트 하이드로클로라이드(methylphenidate hydrochloride)，메틸프레드니솔론(methylprednisolone)，메틸프레드니솔론 아세포네이트(methylprednisolone aceponate)，메틸티오니늄 클로라이드(methylthioninium chloride)，메티로신(metirosine)，메토클로프라미드(metoclopramide)，메토프롤올(metoprolol)，메토프롤올 숙시네이트(metoprolol succinate)，메트리포네이트(metrifonate)，메트로니다졸(metronidazole)，메티라폰(metyrapone)，멕실레틴(mexiletine)，미베프라딜(mibefradil)，미코나졸(miconazole)，미코나졸 나이트레이트(miconazole nitrate)，미다졸람(midazolam)，미다졸람 하이드로클로라이드(midazolam hydrochloride)，미도드린(midodrine)，미도스타우린(midostaurin)，미파무르티드(mifamurtide)，미페프리스톤(mifepristone)，미갈라스타트(migalastat)，미글리톨(miglitol)，미글루스타트(miglustat)，밀나시프란(milnacipran)，밀리논(milrinone)，밀테포신(miltefosine)，미나프린(minaprine)，미노사이클린(minocycline)，미노사이클린 하이드로클로라이드(minocycline hydrochloride)，미도드론산(minodronic acid)，미녹시딜(minoxidil)，미라베그론(mirabegron)，미리플라틴 하이드레이트(miriplatin hydrate)，미로데나필(mirodenafil)，미로데나필 하이드로클로라이드(mirodenafil hydrochloride)，미로가발린(mirogabalin)，미르타자핀(mirtazapine)，미소프로스톨(misoprostol)，미티글리니드(mitiglinide)，미토마이신(mitomycin)，미토옥산트론(mitoxantrone)，미토옥산트론 하이드로클로라이드(mitoxantrone hydrochloride)，미보틸레이트(mivotilate)，미졸라스틴(mizolastine)，미조리빈(mizoribine)，모세티노스타트 다이하이드로브로마이드(mocetinostat dihydrobromide)，모클로베미드(moclobemide)，모다피닐(modafinil)，독시사이클린(doxycycline)，모디파판트(modipafant)，모엑시프릴(moexipril)，모페졸락(mofezolac)，몰리두스타트(molidustat)，몰린돈 하이드로클로라이드(molindone hydrochloride)，모멜로티닙(momelotinib)，모메타손(mometasone)，모네판텔(monepantel)，모노암모늄 글리시르히지네이트(monoammonium glycyrrhizinate)，모노벤존(monobenzone)，모노소듐 알파루미놀(monosodium alphaluminol)，모노테르펜 퍼릴일 알코올(monoterpene perillyl alcohol)，몬테루카스트(montelukast)，몬테루카스트 소듐(montelukast sodium)，몬트몰리로나이트(montmorillonite)，모라시진(moracizine)，모리니다졸(morinidazole)，모르핀(morphine)，모르핀 글루쿠로니드(morphine glucuronide)，모르핀 피타바스타틴(morphine pitavastatin)，모르핀 설페이트(morphine sulfate)，모르포티아딘 메실레이트(morphothiadine mesilate)，모사프리드(mosapride)，모톨리모드(motolimod)，목시덱틴(moxidectin)，목시플록사신(moxifloxacin)，목시플록사신 하이드로클로라이드(moxifloxacin hydochloride)，목소니딘(moxonidine)，목소니딘 하이드로클로라이드(moxonidine hydrochloride)，모자밥탄(mozavaptan)，무파르포스타트 소듐(muparfostat sodium)，무피로신(mupirocin)，마이코박토비르(mycobactovir)，마이코페놀라테모페틸(mycophenolatemofetil)，미리스틸니코티네이트(myristylnicotinate)，나빌론(nabilone)，나빅시몰(nabiximols)，나부메톤(nabumetone)，N-아세틸시스테인(N-acetylcysteine)，나시스텔린(nacystelyn)，나디플록사신(nadifloxacin)，나돌올(nadolol)，나드로파린 칼슘(nadroparin calcium)，나프티핀 하이드로클로라이드(naftifine hydrochloride)，나프토피딜(naftopidil)，날부핀(nalbuphine)，날부핀 세바케이트(nalbuphine sebacate)，날데메딘(naldemedine)，날푸라핀(nalfurafine)，날메펜(nalmefene)，날록세골(naloxegol)，날록손(naloxone)，날록손 하이드로클로라이드(naloxone hydrochloride)，날트렉손(naltrexone)，날트렉손 하이드로클로라이드(naltrexone hydrochloride)，날루조탄(naluzotan)，난드롤론 데카노에이트(nandrolone decanoate)，나파부카신(napabucasin)，나파졸린(naphazoline)，나프토퀴인(naphthoquine)，나프록센(naproxen)，나프록센 소듐(naproxen sodium)，나퀴오티닙 메실레이트(naquotinib mesylate)，나라트립탄(naratriptan)，나르라프레비르(narlaprevir)，나사파퀴(nasapaque)，나사루플라세(nasaruplase)，나스토라제피드 칼슘(nastorazepide calcium)，나테글리니드(nateglinide)，나바메펜트(navamepent)，나자르티닙(nazartinib)，네비볼올(nebivolol)，네쿠파라닙(necuparanib)，네다플라틴(nedaplatin)，네도크로밀(nedocromil)，넬라라빈(nelarabine)，넬피나비르(nelfinavir)，넬로탄세린(nelotanserin)，네모나프리드(nemonapride)，네모녹사신(nemonoxacin)，네오안드로그라폴리드(neoandrographolide)，네오사지톡신(neosaxitoxin)，네오스티그민 메틸설페이트(neostigmine methylsulfate)，네파두탄트(nepadutant)，네파페낙(nepafenac)，네피카스타트(nepicastat)，네포롱(nepolong)，네라멕세인(neramexane)，네라티닙(neratinib)，네리드론산(neridronic acid)，네타르수딜(netarsudil)，네틸미신(netilmicin)，네투피탄트(netupitant)，네비라핀(nevirapine)，니아신(niacin)，니카르디핀(nicardipine)，니세르골린(nicergoline)，니코란딜(nicorandil)，니코티플로린(nicotiflorin)，니코틴(nicotine)，니코틴산(nicotinic acid)，니코수아마이드(nicousamide)，니페디핀(nifedipine)，니페칼란트(nifekalant)，니페비록(nifeviroc)，니푸르티목시(Nifurtimox)，니푸르지드(nifurzide)，니코마이신(nikkomycin)，닐로티닙(nilotinib)，닐루트아마이드(nilutamide)，닐바디핀(nilvadipine), 니메술리드(nimesulide)，니모디핀(nimodipine)，니모라졸(nimorazole)，닌게티닙(ningetinib)，닌테다닙(nintedanib)，니라파립(niraparib)，니솔디핀(nisoldipine)，니타족사니드(nitazoxanide)，니티시논(nitisinone)，니트렌디핀(nitrendipine)，니트리콕사이드(nitricoxide)，나이트로글리세린(nitroglycerin)，니자티딘(nizatidine)，녹자반(nokxaban)，놀라트렉세드(nolatrexed)，노메게스트롤 아세테이트(nomegestrol acetate)，노렐게스트로민(norelgestromin)，노르에피네피린(norepinephrine)，노르에틴드론(norethindrone)，노르에틴드론 아세테이트(norethindrone acetate)，노르에틴드론 에난테이트(norethindrone enantate)，노르에티스테론(norethisterone)，노르에티스테론 아세테이트(norethisterone acetate)，노르플록사신(norfloxacin)，노르게스티메이트(norgestimate)，노리보가인(noribogaine)，노루소데옥시콜산(norursodeoxycholic acid)，오베티콜산(obeticholic acid)，옥테니딘(octenidine)，옥토하이드로아미노아크리딘 숙시네이트(octohydroaminoacridine succinate)，옥트레오티드(octreotide)，옥트레오티드 하이드로클로라이드(octreotide hydrochloride)，오달라스비르(odalasvir)，오다나카팁(odanacatib)，오디파르실(odiparcil)，오플록사신(ofloxacin)，올란자핀(olanzapine)，올라파립(olaparib)，올레스옥심(olesoxime)，올리세리딘(oliceridine)，올메사르탄(olmesartan)，올메사르탄 실레제틸(olmesartan cilexetil)，올메사르탄 메독소밀(olmesartan medoxomil)，올로다테롤(olodaterol)，올로다테롤 하이드로클로라이드(olodaterol hydrochloride)，올로파타딘(olopatadine)，올로파타딘 하이드로클로라이드(olopatadine hydrochloride)，올프리논(olprinone)，올사라진(olsalazine)，올티프라즈(oltipraz)，오마세탁심 메페숙시네이트(omacetaxine mepesuccinate)，오마다사이클린(omadacycline)，오마리글립틴(omarigliptin)，오마벨옥솔론(omaveloxolone)，옴비타스비르(ombitasvir)，오메캄티브메카르빌(omecamtivmecarbil)，오메가-3카복실산(omega-3carboxylic acids)，오메프라졸(omeprazole)，오미가필(omigapil)，오모코나졸(omoconazole)，오날레스핍(onalespib)，오나프리스톤(onapristone)，온단세트론(ondansetron)，온델로프란(ondelopran)，오피카폰(opicapone)，오피프라몰(opipramol)，메틸페니데이트(methylphenidate)，오르시노시드(orcinoside)，오릴로티모드(orilotimod)，오리타반신(oritavancin)，올리스타트(orlistat)，오르니틴 페닐아세테이트(ornithine phenylacetate)，오르노프로스틸(ornoprostil)，오르타탁셀(ortataxel)，오르테로넬(orteronel)，오르토비식(orthovisc)，오르베피탄트(orvepitant)，오셀타미비르(oseltamivir)，오실로드로스타트(osilodrostat)，오시메르티닙(osimertinib)，오시리스 펠룸 프라텐스(Osiris Phleum pratense)，오스페미펜(ospemifene), 오테라실 포타슘(oteracil potassium)，에테세코나졸(oteseconazole)，옥살리플라틴(oxaliplatin)，옥살로아세트산(oxaloacetic acid)，옥산드롤론(oxandrolone)，옥사제팜(oxazepam)，옥스카르바제핀(oxcarbazepine)，옥스펜다다졸(oxfendazole)，옥시디제드글루타티온 소듐(oxidizedglutathione sodium)，옥시라세탐(oxiracetam)，옥시부티닌(oxybutynin)，옥시부티닌 하이드로클로라이드(oxybutynin hydrochloride)，옥시코돈(oxycodone)，옥시코돈 하이드로클로라이드(oxycodone hydrochloride)，옥시메타졸린(oxymetazoline)，옥시메타졸린 하이드로클로라이드(oxymetazoline hydrochloride)，옥시모르폰(oxymorphone)，옥시토신(oxytocin)，오자그렐(ozagrel)，오자그렐 하이드로클로라이드(ozagrel hydrochloride)，오자그렐소듐(ozagrelsodium)，오자니모드(ozanimod)，오제녹사신(ozenoxacin)，파클리탁셀(paclitaxel)，파클리탁셀 폴리글루멕스(paclitaxel poliglumex)，파크리티닙(pacritinib)，팔보시클립(palbociclib)，팔리페리돈(paliperidone)，팔리페리돈 팔미테이트(paliperidone palmitate)，팔미드롤(palmidrol)，팔로노세트론(palonosetron)，팔로바로텐(palovarotene)，파미드로네이트 다이소듐(pamidronate disodium)，판크레리파아제(pancrelipase)，파니페넴(panipenem)，파노비노스타트(panobinostat)，판토프라졸(pantoprazole)，파라세타몰(paracetamol)，파레콕시브(parecoxib)，파리칼시톨(paricalcitol)，파리타프레비르(paritaprevir)，파르나파린 소듐(parnaparin sodium)，파로그렐일(parogrelil)，파로모마이신(paromomycin)，파록세틴(paroxetine)，파록세틴 하이드로클로라이드 헤미하이드레이트(paroxetine hydrochloride hemihydrate)，파록세틴 메실레이트(paroxetine mesylate)，파티로머 칼슘(patiromer calcium)，파투필론(patupilone)，파조파닙(pazopanib)，파주플록사신(pazufloxacin)，파주플록사신 메실레이트(pazufloxacin mesylate)，페프칼시톨(pefcalcitol)，페피시티닙(peficitinib)，페길라테다포-필그라스팀(pegylatedapo-filgrastim)，펠루비프로펜(pelubiprofen)，페마피브레이트(pemafibrate)，페메트렉세드 다이소듐(pemetrexed disodium)，페미로라스트(pemirolast)，페미로라스트 포타슘(pemirolast potassium)，페미로라스트 소듐(pemirolast sodium)，펜사이클로비르(penciclovir)，페네하이클리딘 하이드로클로라이드(penehyclidine hydrochloride)，펜타아미딘(pentamidine)，펜테테이트 칼슘 트라이소듐(pentetate calcium trisodium)，펜테테이트징크 트라이소듐(pentetatezinc trisodium)，펜테트라졸(pentetrazol)，펜토산 폴리설페이트 소듐(pentosan polysulfate sodium)，펜토스타틴(pentostatin)，펜톡시필린(pentoxifylline)，퍼아미비르(peramivir)，퍼암파넬(perampanel)，퍼클로존(perchlozone)，퍼레티노인(peretinoin)，퍼플레나펜트(perflenapent)，퍼플루브론에멀젼(perflubronemulsion)，퍼플루오로옥틸 브로마이드(perfluorooctyl bromide)，퍼골리드(pergolide)，퍼헥실린 말레이트(perhexiline maleate)，페리포스핀(perifosine)，페리도프릴(perindopril)，페리도프릴 아르기닌(perindopril arginine)，퍼로스피론(perospirone)，페보네디스타트(pevonedistat)，펙시다르티닙(pexidartinib)，파고바이오덤(PhagoBioDerm)，펜클로로벤피론(phenchlobenpyrrone)，펜에틸 아이소티오시아네이트(phenethyl isothiocyanate)，페녹시벤즈아민 하이드로클로라이드(phenoxybenzamine hydrochloride)，펜터민(phentermine)，펜터민 하이드로클로라이드(phentermine hydrochloride)，펜톨아민 메실레이트(phentolamine mesylate)，페닐부티레이트(phenylbutyrate)，페닐에프린(phenylephrine)，페닐에프린 하이드로클로라이드(phenylephrine hydrochloride)，펜토인(phenytoin)，포스파지드(phosphazid)， 피브렌타스비르(pibrentasvir)，피시바닐(picibanil)，피크롤리브(picroliv)，피크로포도필린(picropodophyllin)，피도티모드(pidotimod)，필로카르핀(pilocarpine)，필로카르핀 하이드로클로라이드(pilocarpine hydrochloride)，필시카이니드(pilsicainide)，피마세르팁 하이드로클로라이드(pimasertib hydrochloride)，피마반세린(pimavanserin)，피메크롤리무스(pimecrolimus)，피모벤단(pimobendan)，피노셈브린(pinocembrin)，피노메토스타트(pinometostat)，피오글리타존(pioglitazone)，피오글리타존 하이드로클로라이드(pioglitazone hydrochloride)，피팜페론(pipamperone)，피페쿠로늄(pipecuronium)，피페라실린(piperacillin)，피페라실린 소듐(piperacillin sodium)，피페라퀴인(piperaquine)，피페라퀴인 포스페이트(piperaquine phosphate)，피페리돈 하이드로클로리듐(piperidone hydrochloridum)，피페리딘(piperine)，피페르펜톤아민(piperphentonamine)，피라세탐(piracetam)，피라루비신(pirarubicin)，피르페니돈(pirfenidone)，피르메놀(pirmenol)，피로멜라틴(piromelatine)，피로티닙(pirotinib)，피록시캄(piroxicam)，피록시캄베타덱스(piroxicambetadex)，피타바스타틴(pitavastatin)，피타바스타틴 칼슘(pitavastatin calcium)，피토리산트(pitolisant)，픽산트론(pixantrone)，플라조미신(plazomicin)，플레코나릴(pleconaril)，플레릭사포르(plerixafor)，플리나불린(plinabulin)，포카파비르(pocapavir)， 하이드로모르폰(hydromorphone)，포도필옥스(podofilox)，폴라프레징크(polaprezinc)，폴마콕시브(polmacoxib)，폴리다틴(polydatin)，폴리옥시도늄(polyoxidonium)，포마글루메타드 메티오닐(pomaglumetad methionil)，포말리도미드(pomalidomide)，포나티닙(ponatinib)，포네시모드(ponesimod)，포르피머 소듐(porfimer sodium)，포사코나졸(posaconazole)，포시펜(posiphen)，중탄산 나트륨(potassium bicarbonate), 포타슘 시트레이트(potassium citrate)，포타슘 클라불라네이트(potassium clavulanate)，포지오티닙(poziotinib)，프라시노스타트(pracinostat)，프라데포비르(pradefovir)，프랄라트렉세이트(pralatrexate)，프라미펙솔(pramipexole)，프라미르아세탐(pramiracetam)，프란루카스트(pranlukast)，프란루카스트 하이드레이트(pranlukast hydrate)，프라스테론(prasterone)，프라수그렐(prasugrel)，프라바스타틴(pravastatin)，프라조신(prazosin)，프레드니무스틴(prednimustine)，프레드니솔론(prednisolone)，프레드니솔론아세테이트(prednisoloneacetate)，프레드니솔론 소듐포스페이트(prednisolone sodiumphosphate)，프레드니손(prednisone)，프레가발린(pregabalin)，프렘프로(prempro)，프레스타토비르(presatovir)，프레토마니드(pretomanid)，프레비데르신(previdersin)，프렉사세르팁(prexasertib)，프리도피딘(pridopidine)，프릴로케인(prilocaine)，프리텔리비르(pritelivir)，프로카테롤 하이드로클로라이드(procaterol hydrochloride)，프로클로르페라진(prochlorperazine)，프로클로르페라진말레이트(prochlorperazinemaleate)，프로페자임(profezyme)，프로게스테론(progesterone)，프로게스토겐(progestogen)，프로게스토겐다이에노게스트(progestogendienogest)，프로구아닐(proguanil)，프로메타진(promethazine)，프로미틸(promitil)，프로파페논(propafenone)，프로파게르마늄(propagermanium)，프로포폴(propofol)，프로프라놀올(propranolol)，프로프라놀올 하이드로클로라이드(propranolol hydrochloride)，프로스타트(prostat)，프록소돌올(proxodolol)，프루칼로프리드(prucalopride)，프루리프록사신(prulifloxacin)，프루리솔(prurisol)，프루시안블루인솔루블(prussianblueinsoluble)，수도에페드린(pseudoephedrine)，수도에페드린 하이드로클로라이드(pseudoephedrine hydrochloride)，푸에라린(puerarin)，푸퀴티닙 메실레이트(puquitinib mesylate)，피라진아마이드(pyrazinamide)，피리독사민 다이하이드로클로라이드(pyridoxamine dihydrochloride)，피리독신 하이드로클로라이드(pyridoxine hydrochloride)，피리메타민(pyrimethamine)，피로나리딘(pyronaridine)，피롤티닙말레이트(pyrroltinibmaleate)，퀴아제팜(quazepam)，퀴에티아핀 푸마레이트(quetiapine fumarate)，퀴에티아핀(quetiapine)，퀴나골리드 하이드로클로라이드(quinagolide hydrochloride)，퀴나프릴 하이드로클로라이드(quinapril hydrochloride)，퀴니딘 설페이트(quinidine sulfate)，퀴닌 설페이트(quinine sulfate)，퀴누프리스틴(quinupristin)，퀴시노스타트(quisinostat)，퀴자르티닙 다이하이드로클로라이드(quizartinib dihydrochloride)，라베프라졸(rabeprazole)，라베프라졸소듐(rabeprazolesodium)，라벡시모드(rabeximod)，라세카도트릴(racecadotril)，라데졸리드(radezolid)，라도티닙(radotinib)，랄핀아마이드(ralfinamide)，랄리메티닙(ralimetinib)，랄리네파그(ralinepag)，랄옥시펜(raloxifene)，랄테그라비르(raltegravir)，랄티트렉세드(raltitrexed)，라마트로반(ramatroban)，라멜테온(ramelteon)，라미프릴(ramipril)，라모세트론(ramosetron)，라니티딘(ranitidine)，라니티딘 비스무스 시트레이트(ranitidine bismuth citrate)，라놀라진(ranolazine)，라사길린(rasagiline)，라비다스비르 하이드로클로라이드(ravidasvir hydrochloride)，락사트라이진(raxatrigine)，레바미피드(rebamipide)，레바스티닙(rebastinib)，레복세틴(reboxetine)，레복세틴 메실레이트(reboxetine mesylate)，레실리십 소듐(recilisib sodium)，레코플라본(recoflavone)，레다포르핀(redaporfin)，이부프로펜(ibuprofen)，나프록센(naproxen)，글리코피로늄 브로마이드(glycopyrronium bromide)，레파메티닙(refametinib)，레고라페닙(regorafenib)，렐레박탐(relebactam)，렐레노프리드(relenopride)，렐루골릭스(relugolix)，레메글루란트(remeglurant)，레미펜타닐(remifentanil)，레미펜타닐 하이드로클로라이드(remifentanil hydrochloride)，레미마졸람(remimazolam)，레미마졸람 토실레이트(remimazolam tosylate)，레모글리플로진 에타보네이트(remogliflozin etabonate)，레파글리니드(repaglinide)，레파리진(reparixin)，레피리나스트(repirinast)，암렉사녹스(amlexanox)，클로르사이클리진 하이드로클로라이드(chlorcyclizine hydrochloride)，부실아민(bucillamine)，구아나벤즈(guanabenz)，마진돌(mazindol)，날트렉손(naltrexone)，니티시논(nitisinone)，온단세트론(ondansetron)，파세토페레인(phacetoperane)，레티가빈(retigabine)，로시글리타존(rosiglitazone)，소듐 페닐부티레이트(sodium phenylbutyrate)，레시니페라톡신(resiniferatoxin)，레시퀴모드(resiquimod)，레스미노스타트(resminostat)，레스베라트롤(resveratrol)，레타글립틴(retagliptin)，레타파물린(retapamulin)，레티가빈(retigabine)，레티노산(retinoic acid)，레토시반(retosiban)，레바프라잔(revaprazan)，레베페나신(revefenacin)，레비파린 소듐(reviparin sodium)，레인(rhein)，레늄-186 에티드로네이트(rhenium-186 etidronate)，리바비린(ribavirin)，리보사이클립(ribociclib)，리콜리노스타트(ricolinostat)，리디닐라졸(ridinilazole)，리도스틴(ridostin)，리파부틴(rifabutin)，리파암피신(rifampicin)，리파마이신(rifamycin)，리파펜틴(rifapentine)，리팍시민(rifaximin)，리고세르팁 소듐(rigosertib sodium)，릴라플라딥(rilapladib)，릴피비린(rilpivirine)，릴피비린 하이드로클로라이드(rilpivirine hydrochloride)，릴루졸(riluzole)，리만타딘(rimantadine)，리메포리드(rimeporide)，리멕솔론(rimexolone)，리오시구아트(riociguat)，리파수딜 하이드로클로라이드 하이드레이트(ripasudil hydrochloride hydrate)，리세드로네이트 소듐(risedronate sodium)，리스페리돈(risperidone)，리토나비르(ritonavir)，리바록사반(rivaroxaban)，리바스티그민(rivastigmine)，리비판셀 소듐(rivipansel sodium)，리자트립탄(rizatriptan)，리자트립탄 벤조에이트(rizatriptan benzoate)，루물라티온(rmulation)，로실레티닙(rociletinib)，로플루밀라스트(roflumilast)，로키타마이신(rokitamycin)，롤라피탄트(rolapitant)，로무르티드(romurtide)，로나칼레렛(ronacaleret)，로네파르스타트(roneparstat)，로노프테린(ronopterin)，로피니롤(ropinirole)，로피니롤 하이드로클로라이드(ropinirole hydrochloride)，로피바케인(ropivacaine)， 로세벤갈 소듐(rosebengal sodium)，로시글리타존(rosiglitazone)，로시글리타존 말레에이트(rosiglitazone maleate)，로시글리타존 소듐(rosiglitazone sodium)，로스타푸록신(rostafuroxin)，로수바스타틴(rosuvastatin)，로수바스타틴 칼슘(rosuvastatin calcium)，로티고틴(rotigotine)，로바티렐린(rovatirelin)，록사두스타트(roxadustat)，록시트로마이신(roxithromycin)，루비테칸(rubitecan)，루카파립 포스페이트(rucaparib phosphate)，루핀아마이드(rufinamide)，루플록사신(rufloxacin)，루파타딘(rupatadine)，룩소리티닙(ruxolitinib)，S-(-)-오르니다졸 포스페이트 다이소듐(S-(-)-ornidazole phosphate disodium)，사바루비신(sabarubicin)，사쿠비트릴(sacubitril)，사핀아마이드(safinamide)，살부타몰(salbutamol)，살부타몰 설페이트(salbutamol sulfate)，살리사이클산(salicyclic acid)，살메테롤(salmeterol)，살메테롤 지나포에이트(salmeterol xinafoate)，살루브리날(salubrinal)，살비신(salvicine)，사마륨(153Sm) 렉시드로남(samarium(153Sm) lexidronam)，사미도르판(samidorphan)，S-암로디핀 니코티네이트(S-amlodipine nicotinate)，사팍시타빈(sapacitabine)，사프로프테린(sapropterin)，사프로프테린 다이하이드로클로라이드(sapropterin dihydrochloride)，사퀴나비르(saquinavir)，사라카티닙(saracatinib)，사레사이클린(sarecycline)，사로글리타자르(saroglitazar)，사르포그렐레이트 하이드로클로라이드(sarpogrelate hydrochloride)，사볼리티닙(savolitinib)，사자그립틴(saxagliptin)，스코폴아민(scopolamine)，스콜피온베놈(scorpionvenom)， 오메가-3 폴리포화 지방산(omega-3polyunsaturated fatty acid)，섹니다졸(secnidazole)，세게스테론 아세테이트(segesterone acetate)，셀레길린(selegiline)，셀레길린 하이드로클로라이드(selegiline hydrochloride)，셀레프레신(selepressin)，셀렉지파그(selexipag)，셀리사이클립(seliciclib)，셀리넥소르(selinexor)，셀리시스타트(selisistat)，셀루메티닙(selumetinib)，셀루람파넬(selurampanel)，세프라놀론(sepranolone)，세라트로다스트(seratrodast)，세르로피탄트(serlopitant)，세르타코나졸(sertaconazole)，세르타코나졸 나이트레이트(sertaconazole nitrate)，세르트인돌(sertindole)，세르트랄린(sertraline)，세르트랄린 하이드로클로라이드(sertraline hydrochloride)，세티피프란트(setipiprant)，세베라머 카보네이트(sevelamer carbonate)，세베라머 하이드로클로라이드(sevelamer hydrochloride)，세비테로넬(seviteronel)，세보플루레인(sevoflurane)，세부파린 소듐(sevuparin sodium)，시부트라민 말레에이트(sibutramine maleate)，시부트라민 메실레이트(sibutramine mesylate)，실데나필(sildenafil)，실데나필 시트레이트(sildenafil citrate)，실리비닌 다이하이드로젠 숙시네이트(silibinin dihydrogen succinate)，실미타세르팁(silmitasertib)，실로도신(silodosin)，실버 설파디아진(silver sulfadiazine)，시메프레비르(simeprevir)，심미테칸 하이드로클로라이드(simmitecan hydrochloride)，심토티닙 하이드로클로라이드(simotinib hydrochloride)，심바스타틴(simvastatin)，시노테시안(sinotecean)，시포니모드(siponimod)，시롤리무스(sirolimus)，시타플록사신(sitafloxacin)，시타글립틴(sitagliptin)，시타글립틴 포스페이트(sitagliptinphosphate)，시벨레스타트(sivelestat)，시조피란(sizofiran)， 스밀라게닌(smilagenin)，S-모다피닐(S-modafinil)，소부즈옥세인(sobuzoxane)，소듐 에이스시네이트(sodium aescinate)，소듐 아스코르베이트(sodium ascorbate)，소듐 벤조에이트(sodium benzoate)，소듐 바이카보네이트(sodium bicarbonate)，소듐 크로모글리케이트(sodium chromoglycate)，소듐 페릭글루코네이트 착물(sodium ferricgluconate complex)，소듐 글리시디다졸(sodium glycididazole)，소듐 구알레네이트(sodium gualenate)，소듐 히알루로네이트(sodium hyaluronate)，소듐 이반드로네이트(sodium ibandronate)，소듐 나이트레이트(sodium nitrate)，소듐 나이트라이트(sodium nitrite)， 소듐 옥시베이트(sodium oxybate)，소듐 페닐아세테이트(sodium phenylacetate)，소듐 페닐부티레이트(sodium phenylbutyrate)，소듐 폴리설티오네이트(sodium polysulthionate)，소듐 프라스테론설페이트(sodium prasteronesulfate)，소듐 피루베이트(sodium pyruvate)，소듐 타우로콜레이트(sodium taurocholate)，소듐 티오설페이트(sodium thiosulfate)，소듐 지르코늄사이클로실리케이트(sodium zirconiumcyclosilicate)，서포스부비르(sofosbuvir)，소프피로늄 브로마이드(sofpironium bromide)，솔라베그론(solabegron)，솔리페나신(solifenacin)，솔리트로마이신(solithromycin)，소니데깁(sonidegib)，소놀리십(sonolisib)，소포카르핀(sophocarpine)，소포리딘 하이드로클로라이드(sophoridine hydrochloride)，소라페닙(sorafenib)，소르비톨(sorbitol)，소타글리플로진(sotagliflozin)，소티리모드(sotirimod)，소트라스타우린(sotrastaurin)，소틸리즈(sotylize)，소바프레비르(sovaprevir)，스파르플록사신(sparfloxacin)，스파르센탄(sparsentan)，스페부루티닙(spebrutinib)，시피라프릴(spirapril)，스피로노락??(spironolactone)，스쿠알아민(squalamine)，스탄소포르핀(stannsoporfin)，스타부딘(stavudine)，S-테나토프라졸(S-tenatoprazole)，스테프로닌(stepronin)，스티리펜톨(stiripentol)，스트렙토조신(streptozocin)，스트론튬 말로네이트(strontium malonate)，스트론튬 라넬레이트(strontium ranelate)，숙신산(succinic acid)，수크랄페이트(sucralfate)，수크로페릭 옥시하이드록사이드(sucroferric oxyhydroxide)，수펜타닐(sufentanil)，수프탈란징크(suftalanzinc)，수감마덱스(sugammadex)，술박탐(sulbactam)，술박탐 소듐(sulbactam sodium)，술카르딘 설페이트(sulcardine sulfate)，설파메톡시피라진(sulfamethoxypyrazine)，설파살라진(sulfasalazine)，설파티닙(sulfatinib)，설폰일우레아(sulfonylurea)，설포라페인(sulforaphane)，설포탄시논 소듐(sulfotanshinone sodium)，설린닥(sulindac)，설로덱시드(sulodexide)，설파메톡사졸(sulphamethoxazole)，설티암(sulthiame)，수마트립탄(sumatriptan)，수마트립탄 숙시네이트(sumatriptan succinate)，수니티닙(sunitinib)，선스톤(sunstone)，수플라신(suplasyn)，수플라스타트 토실레이트(suplatast tosilate)，수라민 소듐(suramin sodium)，베라파밀 하이드로클로라이드(verapamil hydrochloride)，릴피비린(rilpivirine)，수테졸리드(sutezolid)，수보렉산트(suvorexant)，타칼시톨(tacalcitol)，타크린(tacrine)，타크롤리무스(tacrolimus)，타달라필(tadalafil)，타파아미디스(tafamidis)，타페노퀴인(tafenoquine)，타플루프로스트(tafluprost)，타폭시파린 소듐(tafoxiparin sodium)，탈라데깁(taladegib)，탈라포르핀(talaporfin)，탈라조파립(talazoparib)，탈리펙솔(talipexole)，탈티렐린(taltirelin)，타미바로텐(tamibarotene)，타목시펜(tamoxifen)，탐설로신(tamsulosin)，탐설로신 하이드로클로라이드(tamsulosin hydrochloride)，탄도스피론(tandospirone)，타네스피마이신(tanespimycin)，타펜타돌(tapentadol)，타라페나신(tarafenacin)，타렌플루빌(tarenflurbil)，탈옥소티닙 브로마이드(tarloxotinib bromide)，타셀리십(taselisib)，타시멜테온(tasimelteon)，타시퀴니모드(tasquinimod)，타바보롤(tavaborole)，타빌레르미드(tavilermide)，타자로텐(tazarotene)，타제메토스타트(tazemetostat)，타조박탐(tazobactam)，타조박탐 소듐(tazobactam sodium)，테비페넴 피복실(tebipenem pivoxil)，테카르파린(tecarfarin)，테코비리마트(tecovirimat)，테코리게닌 소듐 설포네이트(tectorigenin sodiumsulfonate)，테디사밀(tedisamil)，테티졸리드 포스페이트(tedizolid phosphate)，테피노스타트(tefinostat)，테가푸르(tegafur)，테가세로드(tegaserod)，테이코플라닌(teicoplanin)，텔라프레비르(telaprevir)，텔라프레비르 아세테이트(telapristone acetate)，텔라티닙(telatinib)，텔비부딘(telbivudine)，텔리트로마이신(telithromycin)，텔미사르탄(telmisartan)，텔로트라이스타트에티프레이트(telotristatetiprate)，테마노그렐(temanogrel)，테모카프릴(temocapril)，테모포르핀(temoporfin)，테모졸로미드(temozolomide)，템시롤리무스(temsirolimus)，테나리십(tenalisib)，테나파노르(tenapanor)，테넬리글립틴(teneligliptin)，테노포비르(tenofovir)，테노포비르알라펜아미이드(tenofoviralafenamide)，테노포비르다이피복실 푸마레이트(tenofovirdipivoxil fumarate)，테노포비르 다이소프록실 아스파르테이트(tenofovir disoproxil aspartate)，테노포비르 다이소프록실 푸마레이트(tenofovir disoproxil fumarate)，테녹시캄(tenoxicam)，테포티닙(tepotinib)，테프레논(teprenone)，테라메프로콜(terameprocol)，테라조신(terazosin)，테르비나핀(terbinafine)，테르비나핀 하이드로클로라이드(terbinafine hydrochloride)，테르구리드(terguride)，테리플루노미드(teriflunomide)，테세바티닙(tesevatinib)，테소펜신(tesofensine)，테스토스테론(testosterone)，테스토스테론 운데카노에이트(testosterone undecanoate)，테트라베나진(tetrabenazine)，테트라케인(tetracaine)，테트라케인 하이드로클로라이드(tetracaine hydrochloride)， 테트라하이드로칸나바이다이올(tetrahydrocannabidiol)，테트라티오몰리브데이트(tetrathiomolybdate)，테트리졸린(tetryzoline)，테자카프토르(tezacaftor)，탈리도미드(thalidomide)，델리아티닙(theliatinib)，데오필린(theophylline)，치료제(therapeutic)，티아지드(thiazide)，티엔노르핀 하이드로클로라이드(thienorphine hydrochloride)，티오테파(thiotepa)，트롬빈(thrombin)，트롬보레둑틴(thromboreductin)，티록신(thyroxine)，티아가빈(tiagabine)，티아넵틴(tianeptine)，티볼론(tibolone)，티카그렐로르(ticagrelor)，티클로피딘(ticlopidine)，티게사이클린(tigecycline)，틸루드로네이트 다이소듐(tiludronate disodium)，티몰올(timolol)，티몰올 말레이트(timolol maleate)，틴다막스(tindamax)，티니다졸(tinidazole)，틴자파린 소듐(tinzaparin sodium)，티오코나졸(tioconazole)，티오프로닌(tiopronin)，티오트로피움 브로마이드(tiotropium bromide)，티오트로피움 브로마이드 모노하이드레이트(tiotropium bromide monohydrate)，티펠루카스트(tipelukast)，티페피딘 하이벤제이트(tipepidine hibenzate)，티피파르닙(tipifarnib)，티피라실 하이드로클로라이드(tipiracil hydrochloride)，티프라나비르(tipranavir)，티라파자민(tirapazamine)，티라셈티브(tirasemtiv)，티릴라자드(tirilazad)，티로피반(tirofiban)，티로피반 하이드로클로라이드(tirofiban hydrochloride)，티반티닙(tivantinib)，티보자닙(tivozanib)，티자니딘(tizanidine)，토브라마이신(tobramycin)，토코페르솔란(tocofersolan)，토코레티네이트(tocoretinate)，토파시티닙(tofacitinib)，토고글리플로진(tofogliflozin)，톨카폰(tolcapone)，톨리미돈(tolimidone)，톨페리손(tolperisone)，톨테로딘(tolterodine)，톨레로딘 타르트레이트(tolterodine tartrate)，톨밥탄(tolvaptan)，토나베르사트(tonabersat)，토피라메이트(topiramate)，토피록소스타트(topiroxostat)，토포테칸(topotecan)，토포테칸 하이드로클로라이드(topotecan hydrochloride)，토라세미드(torasemide)，토레포란트(toreforant)，토레미펜(toremifene)，토세도스타트(tosedostat)，토설플록사신(tosufloxacin)，토트롬보파그(totrombopag)，토자데난트(tozadenant)，트라벡테딘(trabectedin)，트라보데노손(trabodenoson)，트라다이피탄트(tradipitant)，트라마돌(tramadol)，트라모돌(하이드로클로라이드(tramadol hydrochloride)，트라메티닙(trametinib)，트란돌라프릴(trandolapril)，트라넥삼산(tranexamic acid)，트라닐라스트(tranilast)，트랜스크록에티네이트-소듐(transcrocetinate-sodium)，트랜세피텔리알 리보플라빈(transepithelial riboflavin)，트랜틴테롤 하이드로클로라이드(trantinterol hydrochloride)，트라보프로스트(travoprost)，트라조돈(trazodone)，트레할로오스(trehalose)，트레라글립틴 숙시네이트(trelagliptin succinate)，트레오설판(treosulfan)，트레프로스티닐(treprostinil)，트레프로스티닐 다이올아민(treprostinil diolamine)，트레티노인(tretinoin)，트라이암시놀론 아세토니드(triamcinolone acetonide)，트라이아핀(triapine)，트라이아졸람(triazolam)，트라이벤드미딘(tribendimidine)，트라이클로로메티아지드(trichlormethiazide)，트라이시리빈(triciribine)，트라이클라벤다졸(triclabendazole)，트라이클로카르반(triclocarban)，트라이엔틴 하이드로클로라이드(trientine hydrochloride)，트라이파로텐(trifarotene)，트라이플루리딘(trifluridine)，트라이플루살(triflusal)，트라이헵타노인(triheptanoin)，트라이로스테인(trilostane)，트라이메부틴3-티오카바모일-벤젠설포네이트(trimebutine3-thiocarbamoyl-benzenesulfonate)，트라이메부틴 토실레이트(trimebutine tosylate)，트라이메게스톤(trimegestone)，트라이메토프림(trimethoprim)，트라이메트렉세이트(trimetrexate)，트라이나이트레이트(trinitrate)，트라이포타슘 다이시트라토비스무테이트(tripotassium dicitratobismuthate)，트로피네티드(trofinetide)，트로피카미드(tropicamide)，트로피세트론(tropisetron)，트로스피움클로라이드(trospiumchloride)，트로바플록사신(trovafloxacin)，트록시피드(troxipide)，투카티닙(tucatinib)，툴로부테롤(tulobuterol)，틸레르디핀하이드로클로라이드(tylerdipinehydrochloride)，우베니멕스(ubenimex)，우비데카레논(ubidecarenone)， 우브로게판트(ubrogepant)，우데나필(udenafil)，울리나스타틴(ulinastatin)，울리프리스탈(ulipristal)，울리제르티닙(ulixertinib)，울로베타솔(ulobetasol)，우메클리디늄(umeclidinium)，우메클리디늄 브로마이드(umeclidinium bromide)，우파모스타트(upamostat)，우프로세르팁(uprosertib)，우라실(uracil)，우라피딜(urapidil)，우리딘트라이아세테이트(uridinetriacetate)，우로아시티드(uroacitides)，우르소데옥시콜산(ursodeoxycholic acid)，우르솔산(ursolic acid)，바보르박탐(vaborbactam)，바다두스타트(vadadustat)，발라사이클로비르(valaciclovir)，발라사이클로비르 하이드로클로라이드(valaciclovir hydrochloride)，발베나진(valbenazine)，발데콕시브(valdecoxib)，발간사이클로비르(valganciclovir)，발로마사이클로비르 스테아레이트(valomaciclovir stearate)，발프로산(valproic acid)，발루비신(valrubicin)，발사르탄(valsartan)，발사트란 트라이소듐 헤미펜타하이드레이트(valsartan trisodium hemipentahydrate)，반코마이신(vancomycin)，반코마이신 하이드로클로라이드(vancomycin hydrochloride)，반데타닙(vandetanib)，바니프레비르(vaniprevir)，바녹세린(vanoxerine)，바펜다비르(vapendavir)，바르데나필 하이드로클로라이드(vardenafil hydrochloride)，발레니클린(varenicline)，바리테나(varithena)，바르리티닙(varlitinib)，바티퀴논(vatiquinone)，바벨타(vavelta)，벨리파립(veliparib)，벨파타스비르(velpatasvir)，벨루세트라그(velusetrag)，베무라페닙(vemurafenib)，베넥토클락스(venetoclax)，벤라팍심(venlafaxine)，벤라팍심 하이드로클로라이드(venlafaxine hydrochloride)，베폴록사머(vepoloxamer)，베라파밀(verapamil)，베라피밀 하이드로클로라이드(verapamil hydrochloride)，베르디넥소르(verdinexor)，베레겐(veregen)，베리시구아트(vericiguat)，베르누라드(verinurad)，베르나칼란트(vernakalant)，베르나칼란트 하이드로클로라이드(vernakalant hydrochloride)，베로수딜(verosudil)，베르테포르핀(verteporfin)，베루베세스타트(verubecestat)，베루불린(verubulin)，베사톨리모드(vesatolimod)，베스나리논(vesnarinone)，비베그론(vibegron)，비카그렐(vicagrel)，비가바트린(vigabatrin)，빌란테롤(vilanterol)，빌란테롤 트라이페나테이트(vilanterol trifenatate)，빌라프리산(vilaprisan)，빌라조돈(vilazodone)，빌다글립틴(vildagliptin)，빈크리스틴 설페이트(vincristine sulfate)，빈플루닌(vinflunine)，비노렐빈(vinorelbine)，빈포세틴(vinpocetine)，빈타폴리드(vintafolide)，비랄림-C(viralym-C)，비스모데깁(vismodegib)，비스투세르팁(vistusertib)，비타민 E 니코티니케이트(vitamin E nicotinicate)，비조미틴(vizomitin)，보글리보스(voglibose)，볼라세르팁(volasertib)，볼릭시바트 포타슘 에타놀레이트 하이드레이트(volixibat potassium ethanolate hydrate)，보노프라잔 푸마레이트(vonoprazan fumarate)，보라팍사르(vorapaxar)，보리코나졸(voriconazole)，보리노스타트(vorinostat)，보리티옥세틴(vortioxetine)，보리티옥세틴 하이드로브로마이드(vortioxetine hydrobromide)，보사록신(vosaroxin)，복실라프레비르(voxilaprevir)，와파린(warfarin)，제밀로피반(xemilofiban)，이미타스비르(yimitasvir)，욘케나필(yonkenafil)，자보플록사신(zabofloxacin)，자피르루카스트(zafirlukast)，잘시타빈(zalcitabine)，잘레플론(zaleplon)，잘토프로펜(zaltoprofen)，자미카스타트(zamicastat)，자나미비르(zanamivir)，제미스타틴(zemiStatin)，Z-엔독시펜 하이드로클로라이드(Z-endoxifen hydrochloride)，지보텐탄(zibotentan)，디데박탐(zidebactam)，지도부딘(zidovudine)，질레우톤(zileuton)，진카세테이트(zincacetate)，지노스타틴 스티말라머(zinostatin stimalamer)，지프라시돈(ziprasidone)，지페노프릴(zofenopril)，조게닉스(zogenix)，졸레드로네이트 D,L-리신모노하이드레이트(zoledronate D,L-lysinemonohydrate)，졸레드로네이트 다이소듐(zoledronate disodium)，졸레드론산(zoledronic acid)，졸리플로다신(zoliflodacin)，졸미트립탄(zolmitriptan)，졸피뎀(zolpidem)，졸피뎀 타르트레이트(zolpidem tartrate)，조니사미드(zonisamide)，조피클론(zopiclone)，조테핀(zotepine)，주캅사이신(zucapsaicin)，주클로펜티졸(zuclopenthixol)，및 주레티놀 아세테이트(zuretinol acetate)로 이루어진 그룹으로부터 선택된다.
특정 실시태양에서, 전통 중국 의약은 아벨모스치 코롤라(Abelmoschi Corolla), 아브리 허브(Abri Herba), 경마자(Abutili Semen), 오갈피 외피(Acanthopanacis Cortex) 가시오갈피(Acanthopanacis Senticosi Radix Et Rhizoma Seu Caulis), 오갈피 추출물(Acanthopanax Extract), 신초(Achilleae Herba), 우슬(Achyranthis Bidentatae Radix), 초오 박층(Aconiti Kusnezoffii Folium), 천오제(Aconiti Kusnezoffii Radix Cocta), 초오(Aconiti Kusnezoffii Radix), 부자(Aconiti Lateralis Radix Praeparata), 천오제(Aconiti Radix Cocta), 부자(Aconiti Radix), 창포(Acori Calami Rhizoma), 석창포(Acori Tatarinowii Rhizoma), 사삼(Adenophorae Radix), 밤나무 추출물(Aesculi Semen), 살무사(Agkistrodon), 용아초(Agrimoniae Herba), 저백피(Ailanthi Cortex), 조개나물(Ajugae Herba), 목통(Akebiae Caulis), 예지자(Akebiae Fructus), 합환피(Albiziae Cortex), 합환화(Albiziae Flos), 질경이택사(Alismatis Rhizoma), 양파 추출물(Allii Macrostemonis Bulbus), 인경(Allii Sativi Bulbus), 구자(Allii Tuberosi Semen), 알로에(Aloe), 초두구(Alpiniae Katsumadai Semen), 고량강(Alpiniae Officinarum Rhizoma), 익지(Alpiniae Oxyphyllae Fructus), 백반(Alumen), 백두구(Amomi Fructus Rotundus), 사인(Amomi Fructus), 백렴(Ampelopsis Radix), 천심련(Andrographis Herba), 천심련(Andrographolides), 지모(Anemarrhenae Rhizoma), 양두첨(Anemones Raddeanae Rhizoma), 백지(Angelicae Dahuricae Radix), 독활(Angelicae Pubescentis Radix), 당귀(Angelicae Sinensis Radix), 팔각회향(Anisi Stellati Fructus), 나포마엽(Apocyni Veneti Folium), 침향(Aquilariae Lignum Resinatum), 와릉자(Arcae Concha), 우방자(Arctii Fructus), 주사근(Ardisiae Crenatae Radix), 자금우(Ardisiae Japonicae Herba), 대복피(Arecae Pericarpium), 대복피(Arecae Semen Tostum), 빈랑자(Arecae Semen), 천남성(Arisaema Cum Bil), 천남성(Arisaematis Rhizoma Preparatum), 천남성(Arisaematis Rhizoma), 마두령(Aristolochiae Fructus), 천선등(Aristolochiae Herba), 행인(Armeniacae Semen Amarum), 자근(Arnebiae Radix), 청호(Artemisiae Annuae Herba), 애엽(Artemisiae Argyi Folium), 인진호(Artemisiae Scopariae Herba), 세신(Asari Radix Et Rhizoma), 새모래덩굴(Asiatic Moonseed Root Extract), 아교(Asini Corii Colla), 천문동(Asparagi Radix), 구향충(Aspongopus), 자완(Asteris Radix Et Rhizoma), 사원자(Astragali Complanati Semen), 감초(Astragali Radix Praeparata Cum Melle), 황기(Astragali Radix), 백출(Atractylodis Macrocephalae Rhizoma), (Atractylodis Rhizoma), 창출(Aucklandiae Radix), 지각(Aurantii Fructus Immaturus), 지각(Aurantii Fructus), 죽여(Bambusae Caulis In Taenias), 천축황(Bambusae Concretio Silicea), 마람(Baphicacanthis Cusiae Rhizoma Et Radix), 사간(Belamcandae Rhizoma), 벨라돈나 추출물(Belladonna Extract), 벨라돈나 액체 추출물(Belladonna Liquid Extract), 벨로돈나 약초(Belladonnae Herba), 동과피(Benincasae Exocarpium), 안식향(Benzoinum), 세엽소벽(Berberidis Radix), 암백체(Bergeniae Rhizoma), 베르게닌(Bergenin), 권삼(Bistortae Rhizoma), 백급(Bletillae Rhizoma), 토패모(Bolbostemmatis Rhizoma), 백강잠(Bombyx Batryticatus), 용뇌(Borneolum Syntheticum), 용뇌(Borneolum), 인공우황(Bovis Calculus Artifactus), 인공우황(Bovis Calculus Sativus), 우황(Bovis Calculus), 브레비스카핀(Breviscapine), 저실자(Broussonetiae Fructus), 아담자(Bruceae Fructus), 수우각(Bubali Cornu), 밀몽화(Buddlejae Flos), 섬수(Bufonis Venenum), 금전백화사(Bungarus Parvus), 시호(Bupleuri Radix), 노감석(Calamina), 작살나무(Callicarpae Caulis Et Folium), 두홍화(Callicarpae Formosanae Folium), 작살나무(Callicarpae Macrophyllae Folium), 경분(Calomelas), 능소화(Campsis Flos), 감람(Canarii Fructus), 도두(Canavaliae Semen), 화마인(Cannabis Fructus), 고추(Capsici Fructus), 당근(Carotae Fructus), 학슬(Carpesii Fructus), 홍화(Carthami Flos), 정향(Caryophylli Flos), 정향(Caryophylli Fructus), 결명자(Cassiae Semen), 피마자유(Castor Oil), 빈랑(Catechu), 맨드라미(Celosiae Cristatae Flos), 청상자(Celosiae Semen), 병풀(Centella Total Glucosides), 병풀 약초(Centellae Herba), 아불식초(Centipedae Herba), 충백납(Cera Chinensis), 황납(Cera Flava), 녹각상(Cervi Cornu Degelatinatum), 녹용(Cervi Cornu Pantotrichum), 녹각(Cervi Cornu), 녹각교(Cervi Cornus Colla), 목과(Chaenomelis Fructus), 명당삼(Changii Radix), 가자(Chebulae Fructus Immaturus), 가자(Chebulae Fructus), 백굴채(Chelidonii Herba), 중국 당귀 액체 추출물(Chinese Angelica Liquid Extract), 청목석(Chloriti Lapis), 광조(Choerospondiatis Fructus), 감국(Chrysanthemi Flos), 감국(Chrysanthemi Indici Flos), 자연(Chuanxiong Rhizoma), 구척(Cibotii Rhizoma), 선퇴(Cicadae Periostracum), 치커리(Cichorii Herba), 치커리(Cichorii Radix), 승마(Cimicifugae Rhizoma), 주사(Cinnabaris), 육계(Cinnamomi Cortex), 계지(Cinnamomi Ramulus), 시나몬유(Cinnamon Oil), 대계(Cirsii Herba), 대계(Cirsii Japonici Herba), 카보니사타(Carbonisata), 대계(Cirsii Japonici Herba), 석생등(Cissampelotis Herba), 육총용(Cistanches Herba), 길홍(Citri Exocarpium Rubrum), 진피(Citri Fructus), 화귤홍(Citri Grandis Exocarpium), 청피(Citri Reticulatae Pericarpium Viride), 청피(Citri Reticulatae Pericarpium), 귤핵(Citri Reticulatae Semen), 향연(Citri Sarcodactylis Fructus), 천목통(Clematidis Armandii Caulis), 위령선(Clematidis Radix Et Rhizoma), 대화풍륜채(Clinopodii Herba), 미나리과(Cnidii Fructus), 당삼(Codonopsis Radix), 의이인(Coicis Semen), 압척초(Commelinae Herba), 금불초(Conyzae Herba), 황련(Coptidis Rhizoma), 동충하초(Cordyceps), 산수유(Corni Fructus), 고지정(Corydalis Bungeanae Herba), 여강(Corydalis Decumbentis Rhizoma), 향부자(Corydalis Rhizoma), 유기(Crataegi Folium), 유기(Crataegi Fructus), 산자고(Cremastrae Pseudobulbus), 플레이오네스 수도불버스(Pleiones Pseudobulbus), 혈여탄(Crinis Carbonisatus), 샤프란(Croci Stigma), 파두(Crotonis Fructus), 파두상(Crotonis Semen Pulveratum), 선모(Curculiginis Rhizoma), 강황(Curcumae Longae Rhizoma), 울금(Curcumae Radix), 아출(Curcumae Rhizoma), 토사자(Cuscutae Semen), 천우슬(Cyathulae Radix), 사이클로비로북신(Cyclovirobuxine), 백미(Cynanchi Atrati Radix Et Rhizoma), 서장경(Cynanchi Paniculati Radix Et Rhizoma), 백전(Cynanchi Stauntonii Rhizoma Et Radix), 쇄양(Cynomorii Herba), 향부자(Cyperi Rhizoma), 산진달래 잎 오일(Dahurian Rhododendron Leaf Oil), 강향(Dalbergiae Odoriferae Lignum), 양금화(Daturae Flos), 석곡(Dendrobii Caulis), 철피석곡(Dendrobii Officinalis Caulis), 정력자(Descurainiae Semenlepidii Semen), 광금전초(Desmodii Styracifolii Herba), 구맥(Dianthi Herba), 상산(Dichroae Radix), 백선피(Dictamni Cortex), 황산약(Dioscorea Panthaicae Rhizoma), 비해(Dioscoreae Hypoglaucae Rhizoma), 천산룡(Dioscoreae Nipponicae Rhizoma), 산약(Dioscoreae Rhizoma), 산약(Dioscoreae Spongiosae Rhizoma), 속단(Dipsaci Radix), 혈갈(Draconis Sanguis), 골쇄보(Drynariae Rhizoma), 면마(Dryopteridis Crassirhizomatis Rhizoma Carbonisatum), 관중(Dryopteridis Crassirhizomatis Rhizoma), 절굿대(Echinopsis Radix), 한련초(Ecliptae Herba), 귀경 추출물(Entadae Semen), 엔티아네 로단태 약초(Entianae Rhodanthae Herba), 마황(Ephedrae Herba), 마황근(Ephedrae Radix Et Rhizoma), 음양곽(Epimedii Folium), 에피메디 우샤넨시스 박층(Epimedii Wushanensis Folium), 목적(Equiseti Hiemalis Herba), 등잔화(Erigerontis Herba), 에리오보트리애 폴륨(Eriobotryae Folium), 에리오카울리 플로스(Eriocauli Flos), 에로디 허바 게라니 허바(Erodii Herba Geranii Herba), 에리시베스 카울리스(Erycibes Caulis), 유칼립투스 오일(Eucalyptus Oil), 유코미애 코르텍스(Eucommiae Cortex), 유코미애 폴륨(Eucommiae Folium), 유코디애 프룩투스(Euodiae Fructus), 유파토리 허바(Eupatorii Herba), 유파토리 린딜야니 허바(Eupatorii Lindleyani Herba), 유포르비애 에바락테오라태 라딕스(Euphorbiae Ebracteolatae Radix), 유포르비애 히르태 허바(Euphorbiae Hirtae Herba), 유포르비애 휴미푸새 허바(Euphorbiae Humifusae Herba), 유포르비애 페키넨시스 라딕스(Euphorbiae Pekinensis Radix), 유포르비애 지멘 풀베라텀(Euphorbiae Semen Pulveratum), 유로프비애 지멘(Euphorbiae Semen), 유폴리파가 스텔레오파가(Eupolyphaga Steleophaga), 유리알레스 지멘(Euryales Semen), 포가프리 다이보트리스 리히조마(Fagopyri Dibotryis Rhizoma), 파르파래 플로스(Farfarae Flos), 퍼룰래 레시나(Ferulae Resina), 피브라우레애 카울리스(Fibraureae Caulis), 피브리우레티닌(Fibriuretinin), 플루오리텀(Fluoritum), 오에니쿨리 프룩투스(Foeniculi Fructus), 포르신티애 프룩투스(Forsythiae Fructus), 프락시니 코르텍스(Fraxini Cortex), 플리틸라리애 시르호새 불버스(Fritillariae Cirrhosae Bulbus), 플리틸라리애 후펜시스 불버스(Fritillariae Hupehensis Bulbus), 플리틸라리애 팔리디플로래 불버스(Fritillariae Pallidiflorae Bulbus), 플리틸라리애 턴베르기 불버스(Fritillariae Thunbergii Bulbus), 플리틸라리애 우수리엔시스 불버스(Fritillariae Ussuriensis Bulbus), 갈란개 프룩투스(Galangae Fructus), 갈라 차이네시스(Galla Chinensis), 갈리 기저리 엔토텔륨 코르네움(Galli Gigerii Endothelium Corneum), 간도더마(Ganoderma), 카필라리 우드웜 추출물 (Capillary Wormwood Extract), 가르덴니애 프룩투스 프래파라투스(GardeniaeFructus Praeparatus), 가르데니애 프룩투스(Gardeniae Fructus), 가스트로디애 리히조마(Gastrodiae Rhizoma), 게코(Gecko), 게이 허바(Gei Herba), 젠다루새 허바(Gendarussae Herba), 겐카 플로스(Genkwa Flos), 젠티아내 마이크로필래 라딕스(Gentianae Macrophyllae Radix), 젠티아내 라딕스 이티 리히조마(Gentianae Radix Et Rhizoma), 생강 액체 추출물(Ginger Liquid Extract), 은행나무 박층(Ginkgo Folium), 은행나무 잎 추출물(Ginkgo Leaves Extract), 은행나무 추출물(Ginkgo Semen), 인산 박층(Ginseng Folium), 진생 라딕스 이티 리히조마 루브라(Ginseng Radix Et Rhizoma Rubra), 진생 라딕스 이티 리히조마(Ginseng Radix Et Rhizoma), 글라부로스 사르칸드라 추출물(Glabrous Sarcandra Extract), 글렌코매 허바(Glechomae Herba), 글레디트새 프룩투스 앱모말리스(Gleditsiae Fructus Abnormalis), 글레디트새 시넨시스 프룩투스(Gleditsiae Sinensis Fructus), 글레디트새 스피나(Gleditsiae Spina), 글레히니애 라딕스(Glehniae Radix), 글리시르히재 라틱스 이티 리히조마 프래파라타 쿰 멜레(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle), 글리시르히재 라틱스 이티 리히조마(Glycyrrhizae Radix Et Rhizoma), 고삼피니 플로스(Gossampini Flos), 그라나티 페리카르피움(Granati Pericarpium), 깁섬 피브로섬(Gypsum Fibrosum), 깁섬 우스텀(Gypsum Ustum), 해마티텀(Haematitum), 할리오티디스 콘차(Haliotidis Concha), 할리텀(Halitum), 할로이시텀 루브럼(Halloysitum Rubrum), 황트론 잎 추출물(Hawthorn Leave Extract), 헤디사리 라딕스 프래파라타 쿰 멜레(Hedysari Radix Praeparata Cum Melle), 헤디사리 라딕스(Hedysari Radix), 히비스시 무타빌리스 폴륨(Hibisci Mutabilis Folium), 히포캄푸스(Hippocampus), 히포패 프룩투스(Hippophae Fructus), 히루도(Hirudo), 호말로메내 리히조마(Homalomenae Rhizoma), 호로데이 프룩투스 게르마나투스(Hordei Fructus Germinatus), 호우투이니애 허바(Houttuyniae Herba), 하이드라르기리 옥시덤 루브럼(Hydrargyri Oxydum Rubrum), 효스시아미 지멘(Hyoscyami Semen), 하이퍼리시 퍼포라티 허바(Hyperici Perforati Herba), 일리시스 차이네시스 폴륨(Ilicis Chinensis Folium), 일리시스 코르누태 폴륨(Ilicis Cornutae Folium), 일리시스 로툰대 코르텍스(Ilicis Rotundae Cortex), 울리시 코르텍스(Ulicii Cortex), 임파티엔티스 지멘(Impatientis Semen), 임퍼라태 리히조마(Imperatae Rhizoma), 인디고 나투랄리스(Indigo Naturalis), 이눌래 플로스(Inulae Flos), 이눌래 허바(Inulae Herba), 이눌래 라딕스(Inulae Radix), 이리디스 텍토리 리히조마(Iridis Tectori Rhizoma), 이사티디스 폴륨(Isatidis Folium), 이사티디스 라딕스(Isatidis Radix),주저글란디스 지멘(Juglandis Semen), 주주베 프룩투스(Jujubae Fructus), 준시 메둘라(Junci Medulla), 카드수래 카울리스(Kadsurae Caulis), 켐페래 리히조마(Kaempferiae Rhizoma), 카키 칼릭스(Kaki Calyx), 칸수이 라딕스(Kansui Radix), 카복시애 라딕스(Knoxiae Radix), 코치애 프룩투스(Kochiae Fructus), 랩라브 지멘 알범(Lablab Semen Album), 라그저래 허바(Laggerae Herba), 라고티디스 허바(Lagotidis Herba), 라미나래 탈루스 엑크로니애 탈루스(Laminariae Thallus Eckloniae Thallus), 라미오필로미스 허바(Lamiophlomis Herba), 라시오스파에라 칼바티아(Lasiosphaera Calvatia), 레오누리 프룩투스(Leonuri Fructus), 레오누리 허바(Leonuri Herba), 레오누루스 액체 추출물(Leonurus Liquid Extract), 리코리스 추출물(Licorice Extract), 리코리스 액체 추출물(Licorice Liquid Extract), 리구스티시 리히조마 이티 라딕스(Ligustici Rhizoma Et Radix), 리구스트리 루시디 프룩투스(Ligustri Lucidi Fructus), 릴리 불버스(Lilii Bulbus), 리모니텀(Limonitum), 린데래 라딕스(Linderae Radix), 리니 지멘(Lini Semen), 리퀴드암바리스 프룩투스(Liquidambaris Fructus), 리퀴드암바리스 레시나(Liquidambaris Resina), 리리오페스 라딕스(Liriopes Radix), 리트치 지멘(Litchi Semen), 리트새 프룩투스(Litseae Fructus), 로벨리애 차이넨시스 허바(Lobeliae Chinensis Herba), 론간 아릴루스(Longan Arillus), 로니세래 플로스(Lonicerae Flos), 로니세래 자포니캐 카울리스(Lonicerae Japonicae Caulis), 로니세래 자포니캐 플로스(Lonicerae Japonicae Flos), 로파테리 허바(Lophatheri Herba), 루프패 프룩투스 레티너부스(Luffae Fructus Retinervus), 리시 코르텍스(Lycii Cortex), 리시 프룩투스(Lycii Fructus), 리코피 허바(Lycopi Herba), 리코포디 허바(Lycopodii Herba), 리고디 스포라(Lygodii Spora), 리스마치애 허바(Lysimachiae Herba), 리시오노티 허바(Lysionoti Herba), /-보르네올룸(/-Borneolum), /-멘톨(/-Menthol), 마그네티텀(Magnetitum), 마그놀래 플로스(Magnoliae Flos), 마그놀래 오피시날리스 코르텍스(Magnoliae Officinalis Cortex), 마그놀래 오피시날리스 플로스(Magnoliae Officinalis Flos), 마호니애 카울리스(Mahoniae Caulis), 말배 프룩투스(Malvae Fructus), 마니스 스쿠아마(Manis Squama), 만디스 오테카(Mantidis OOTheca), 마그가리타(Margarita), 마르가리티페러 콘차(Margaritifera Concha), 마르스데니애 테나시시매 카울리스(Marsdeniae Tenacissimae Caulis), 멜(Mel), 멜라테리텀(Melanteritum), 멜리애 코르텍스(Meliae Cortex), 멜로 지멘(Melo Semen), 메니스퍼미 리히조마(Menispermi Rhizoma), 멘태 하플로칼리시스 허바(Menthae Haplocalycis Herba), 메레트리시스 콘차(Meretricis Concha), 사이클리내 콘차(Cyclinae Concha), 미캐 리피스 아우레우스(Micae Lapis Aureus), 마이크록티스 폴륨(Microctis Folium), 미라빌리텀 프래파라텀(Mirabilitum Praeparatum), 모노르디캐 지멘(Momordicae Semen), 모리 코르텍스(Mori Cortex), 모리 폴륨(Mori Folium), 모리 프룩투스(Mori Fructus), 모리 라물루스(Mori Ramulus), 모린대 오피시날리스 라딕스(Morindae Officinalis Radix), 모스추스(Moschus), 모스래 허바(Moslae Herba), 모우탄 코르텍스(Moutan Cortex), 무메 플로스(Mume Flos), 무메 프룩투스(Mume Fructus), 머라애 폴륨 이티 카쿠멘(Murrayae Folium Et Cacumen), 마일라브리스(Mylabris), 마이리스티캐 지멘(Myristicae Semen), 마이르하(Myrrha), 나르도스타쵸스 라딕스 이티 리히조마(Nardostachyos Radix Et Rhizoma), 나트리 설파스 엑식카투스(Natrii Sulfas Exsiccatus), 나트리 설파스(Natrii Sulfas), 넬룸비니스 폴륨(Nelumbinis Folium), 넬룸비니스 플루물라(Nelumbinis Plumula), 넬룸비니스 레셉타쿨럼(Nelumbinis Receptaculum), 넬룸비니스 리히조마티스 노두스(Nelumbinis Rhizomatis Nodus), 넬룸비니스 지멘 (Nelumbinis Semen), 넬룸비니스 스타멘(Nelumbinis Stamen), 니겔래 지멘(Nigellae Semen), 노토진센 라딕스 이티 리히조마(Notoginseng Radix Et Rhizoma), 노토진센 토탈 사포닌(Notoginseng Total Saponins), 노토진센 트라이올 사포닌(Notoginseng Triol Saponins), 노토프테리기 리히조마 이티 라딕스(Notopterygii Rhizoma Et Radix), 오시멈 그라티시멈 오일(Ocimum Gratissimum Oil), 올리바눔(Olibanum), 옴팔리아(Omphalia), 오피칼시텀(Ophicalcitum), 오피오포고니스 라딕스(Ophiopogonis Radix), 오로스타치스 핌브리아태 허바(Orostachyis Fimbriatae Herba), 오르옥실리 지멘(Oroxyli Semen), 오리재 프룩투스 게르미나투스(Oryzae Fructus Germinatus), 오스문대 리히조마(Osmundae Rhizoma), 오스트래 콘차(Ostreae Concha), 패오니애 라딕스 알바(Paeoniae Radix Alba), 패오니애 라딕스 루브라(Paeoniae Radix Rubra), 파나시스 저포니시 리히조마(Panacis Japonici Rhizoma), 파나시스 마조리스 리히조마(Panacis Majoris Rhizoma), 파나시스 퀸퀴에폴리 라딕스(Panacis Quinquefolii Radix), 파파베리스 페리카르피움 SI(Papaveris Pericarpium SI), 파리드스 리히조마(Paridis Rhizoma), 파촐울리 오일(Patchouli Oil), 페개오피티 라딕스 이티 리히조마(Pegaeophyti Radix Et Rhizoma), 페퍼민트 오일(Peppermint Oil), 퍼릴래 카울리스(Perillae Caulis), 퍼릴래 폴륨(Perillae Folium), 퍼릴래 프룩투스(Perillae Fructus), 퍼리플로캐 코르텍스(Periplocae Cortex), 퍼시캐 라물루스(Persicae Ramulus), 퍼리캐 지멘(Persicae Semen), 페우세다니 데쿠르시비 라딕스(Peucedani Decursivi Radix), 페우세다니 라딕스(Peucedani Radix), 파르비티디스 지멘(Pharbitidis Semen), 펠로덴드리 아무렌시시 코르텍스(Phellodendri Amurensis Cortex), 펠로덴드리 차이넨시스 코르텍스(Phellodendri Chinensis Cortex), 페레티마(Pheretima), 파라그미티스 리히조마(Phragmitis Rhizoma), 필린티 프룩투스(Phyllanthi Fructus), 필살리스 칼릭스 세우 프룩투스(Physalis Calyx Seu Fructus), 피소칠라이내 라딕스(Physochlainae Radix), 피토락새 라딕스(Phytolaccae Radix), 피크라스매 라물루스 이티 폴륨(Picrasmae Ramulus Et Folium), 피크리애 허바(Picriae Herba), 피크로르히재 리히조마(Picrorhizae Rhizoma), 피넬리애 리히조마 프래파라텀 쿰 알루민(Pinelliae Rhizoma Praeparatum Cum Alumine), 피넬리애 리히조마 프래파라텀 쿰 진지베레 이티 알루민(Pinelliae Rhizoma Praeparatum Cum Zingibere Et Alumine), 피넬리애 리히조마 프래파라텀(Pinelliae Rhizoma Praeparatum), 피넬리애 리히조마(Pinelliae Rhizoma), 피니 리그넘 노디(Pini Lignum Nodi), 피니 폴렌(Pini Pollen), 피퍼리스 프룩투스(Piperis Fructus), 피페리스 카드수래 카울리스(Piperis Kadsurae Caulis), 피페리스 론기 프룩투스(Piperis Longi Fructus), 플랜타기니스 허바(Plantaginis Herba), 플랜타기니스 지멘(Plantaginis Semen), 플라티클라디 카쿠멘(Platycladi Cacumen), 플라티클라디 지멘(Platycladi Semen), 플라티코도니스 라딕스(Platycodonis Radix), 포고스테모니스 허바(Pogostemonis Herba), 폴리갈라 액체 추출물(Polygala Liquid Extract), 폴리갈래 자포니캐 허바(Polygalae Japonicae Herba), 폴리갈래 라딕스(Polygalae Radix), 폴리고나티 오도라티 리히조마(Polygonati Odorati Rhizoma), 폴리고나티 리히조마(Polygonati Rhizoma), 폴리고니 아비쿨라리스 허바(Polygoni Avicularis Herba), 폴리고니 쿠스피다티 리히조마 이티 라딕스(Polygoni Cuspidati Rhizoma Et Radix), 폴리고니 멀티플로리 카울리스(Polygoni Multiflori Caulis), 폴리고니 멀티플로리 라딕스 프래파라타(Polygoni Multiflori Radix Praeparata), 폴리고니 멀티플로리 라딕스(Polygoni Multiflori Radix), 폴리고니 오리엔탈리스 프룩투스(Polygoni Orientalis Fructus), 폴리고니 퍼플리아티 허바(Polygoni Perfoliati Herba), 폴리고니 티닉토리 폴륨(Polygoni Tinctorii Folium), 폴리포루스(Polyporus), 포리아(Poria), 포리애 쿠티스(Poriae Cutis), 포르투라캐 허바(Portulacae Herba), 포텐틸래 차이넨시스 허바(Potentillae Chinensis Herba), 포텐틸래 디스콜로리스 허바(Potentillae Discoloris Herba), 분말 버팔로 뿔 추출물(Powerdered Buffalo Horn Extract), 프린세피애 눅스(Prinsepiae Nux), 프로폴리스(Propolis), 푸루넬래 스피카(Prunellae Spica), 푸루니 지멘(Pruni Semen), 사모실레네스 라딕스(Psammosilenes Radix), 수도라리시스 코르텍스(Pseudolaricis Cortex), 수도스텔라리애 라딕스(Pseudostellariae Radix), 소라리애 프룩투스(Psoraleae Fructus), 프테로세팔리 허바(Pterocephali Herba), 푸에라리애 로바태 라딕스(Puerariae Lobatae Radix), 푸에라리애 톰소니 라딕스(Puerariae Thomsonii Radix), 풀사틸래 라딕스(Pulsatillae Radix), 피리텀(Pyritum), 피로래 허바(Pyrolae Herba), 피로시애 폴륨(Pyrrosiae Folium), 퀴스쿠알리스 프룩투스(Quisqualis Fructus), 라브도시애 루베센티스 허바(Rabdosiae Rubescentis Herba), 라내 오비덕투스(Ranae Oviductus), 러눈쿨리 테르나티 라딕스(Ranunculi Ternati Radix), 라파니 지멘(Raphani Semen), 리얼가르(Realgar), 리히만니애 라딕스 프래파라타(Rehmanniae Radix Praeparata), 리히만니애 라딕스(Rehmanniae Radix), 르하폰티시 라딕스(Rhapontici Radix), 루헤이 라딕스 이티 리히조마(Rhei Radix Et Rhizoma), 로디올래 크레눌라태 라딕스 이티 리히조마(Rhodiolae Crenulatae Radix Et Rhizoma), 로도덴드리 다우리시 폴륨(Rhododendri Daurici Folium), 로도덴드리 몰리스 플로스(Rhododendri Mollis Flos), 대황 추출물(Rhubarb Extract), 대화 액체 추출물(Rhubarb Liquid Extract), 리시니 지멘 (Ricini Semen), 로새 차이넨스 플로스(Rosae Chinensis Flos), 로새 래비가태 프룩투스(Rosae Laevigatae Fructus), 로새 루코새 플로스(Rosae Rugosae Flos), 루비 프룩투스(Rubi Fructus), 루비애 라딕스 이티 리히조마(Rubiae Radix Et Rhizoma), 사이캐 타타리캐 코르누(Saigae Tataricae Cornu), 살비아 토탈 페놀산 (Salvia Total Phenolic Acids), 실비애 밀티오르히재 라딕스 이티 리히조마(Salviae Miltiorrhizae Radix Et Rhizoma), 산구이소르배 라딕스(Sanguisorbae Radix), 산탈리 알비 리그넘(Santali Albi Lignum), 사포신니코비애 라딕스(Saposhnikoviae Radix), 사판 리그넘(Sappan Lignum), 사르칸드래 허바(Sarcandrae Herba), 사르가숨(Sargassum), 사르겐토독새 카울리스(Sargentodoxae Caulis), 사우로피 폴륨(Sauropi Folium), 사우루리 허바(Saururi Herba), 사우수레애 인볼루크라태 허바(Saussureae Involucratae Herba), 스키산드래 차이넨시스 프룩투스(Schisandrae Chinensis Fructus), 스키산드래 스페난테래 프룩투스(Schisandrae Sphenantherae Fructus), 스키조네페태 허바 카르보니사타(Schizonepetae Herba Carbonisata), 스키조네페태 허바(Schizonepetae Herba), 스키조네페태 스피카 카르보니사타(Schizonepetae Spica Carbonisata), 스키조네페태 스피카(Schizonepetae Spica), 스콜로펜드라(Scolopendra), 스콜피오(Scorpio), 스크로풀루라리애 라딕스(Scrophulariae Radix), 수쿠텔라리아 추출물(Scutellaria Extract), 수쿠텔라리아 바르바태 허바(Scutellariae Barbatae Herba), 수쿠텔라릴아 라딕스(Scutellariae Radix), 세디 허바(Sedi Herba), 셀라기넬래 허바(Selaginellae Herba), 세미아퀼레기애 라딕스(Semiaquilegiae Radix), 세넥시오니스 스캔덴티스 허바(Senecionis Scandentis Hebra), 센내 폴륨(Sennae Folium), 스피애 엔도콘차(Sepiae Endoconcha), 서르펜티스 페리오스트라쿰(Serpentis Periostracum), 참깨 오일(Sesame Oil), 세쌔미 지멘 니그룸(Sesami Semen Nigrum), 세타리애 프룩투스 게르미나투스(Setariae Fructus Germinatus), 시에게스벡키애 허바(Siegesbeckiae Herba), 실리비 프룩투스(Silybi Fructus), 시나피스 지멘(Sinapis Semen), 시노메니 카울리스(Sinomenii Caulis), 시노포도필리 프룩투스(Sinopodophylli Fructus), 시포노스테지애 허바(Siphonostegiae Herba), 시라이티애 프룩투스(Siraitiae Fructus), 시밀라시스 차이내 리히조마(Smilacis Chinae Rhizoma), 시밀라시스 글라브래 리히조마(Smilacis Glabrae Rhizoma), 소재 지멘 게르미나텀(Sojae Semen Germinatum), 소재 지멘 니그룸(Sojae Semen Nigrum), 소재 지멘 프래파라텀(Sojae Semen Praeparatum), 솔리다기니스 허바(Solidaginis Herba), 소포래 플라베센티스 라딕스(Sophorae Flavescentis Radix), 소포래 플로스(Sophorae Flos), 소포래 프룩투스(Sophorae Fructus), 소포래 토키넨시스 라딕스 이티 리히조마(Sophorae Tonkinensis Radix Et Rhizoma), 스파르가니 리히조마(Sparganii Rhizoma), 사파톨로비 카울리스(Spatholobi Caulis), 스피셀레프 커넬 오일(Spiceleaf Kernel Oil), 스피로델래 허바(Spirodelae Herba), 스타추리 메둘라 헬윈지애 메둘라(Stachyuri Medulla Helwingiae Medulla), 스타락티텀(Stalactitum), 스타 아니세 오리(Star Anise Oil), 스타운토니애 카울리스 이티 폴륨(Stauntoniae Caulis Et Folium), 스텔라리애 라딕스(Stellariae Radix), 스테모내 라딕스(Stemonae Radix), 스테파니애 테트란드래 라딕스(Stephaniae Tetrandrae Radix), 스테르쿨리애 리치노포래 지멘(Sterculiae Lychnophorae Semen), 스티리친 지멘 풀베라텀(Strychni Semen Pulveratum), 스티리친 지멘(Strychni Semen), 스티락스(Styrax), 스우이스 펠리스 풀비스(Suis Fellis Pulvis), 황(Sulfur), 스위르티애 허바(Swertiae Herba), 스위르티애 밀렌시스 허바(Swertiae Mileensis Herba), 신그나투스(Syngnathus), 시린개 코르텍스(Syringae Cortex), 탈시 풀비스(Talci Pulvis), 활석(Talcum), 타마리시스 카쿠멘(Tamaricis Cacumen), 탄시노네스(Tanshinones), 타라락시 허바(Taraxaci Herba), 탁실리 허바(Taxilli Herba), 차-씨 오일(Tea-Seed Oil), 터미날리애 벨리리캐 프룩투스(Terminaliae Belliricae Fructus), 테스투디니스 카라파시스 이티 플라스트리 콜라(Testudinis Carapacis Et Plastri Colla), 테스투디디니스 카라팍스 이티 플라스트럼(Testudinis Carapax Et Plastrum), 테트라파나시스 메둘라(Tetrapanacis Medulla), 틸라스피 허바(Thlaspi Herba), 썬베르그 프리틸라리 액체 추출물(Thunberg Fritillary Liquid Extract), 티노스포래 라딕스(Tinosporae Radix), 인산 줄기 및 잎의 전체 진세노시드(Toatal Ginsenoside Of Ginseng Stems And Leaves), 토센단 프룩투스(Toosendan Fructus), 토레애 지멘(Torreyae Semen), 전체 진세노시드 인산 뿌리(Total Ginsenoside Ginseng Root), 톡시코덴드리 레시나(Toxicodendri Resina), 트라첼로스퍼르미 카울리스 이티 폴륨(Trachelospermi Caulis Et Folium), 트라치카르피 페티올루스(Trachycarpi Petiolus), 트라이불리 프룩투스(Tribuli Fructus), 트라이초산디스 프룩투스(Trichosanthis Fructus), 트라이초산디스 퍼리카르피움(Trichosanthis Pericarpium), 트라이초산디스 라딕스(Trichosanthis Radix), 트라이초산디스 지멘 토스텀(Trichosanthis Semen Tostum), 트라이초산디스 지멘(Trichosanthis Semen), 트라이고넬래 지멘(Trigonellae Semen), 트라이온시스 카라팍스(Trionycis Carapax), 트사오코 프룩투스(Tsaoko Fructus), 터펜틴 오일(Turpentine Oil), 터피니애 폴륨(Turpiniae Folium), 티패 폴른(Typhae Pollen), 티포니 리히조마(Typhonii Rhizoma), 운카리애 라물루스 쿰 운시스(Uncariae Ramulus Cum Uncis), 박카리애 지멘(Vaccariae Semen), 발레리애내 자타만시 리히조마 이티 라딕스(Valerianae Jatamansi Rhizoma Et Radix), 베르벤 허바(Verbenae Herba), 베스패 니두스(Vespae Nidus), 비그내 지멘(Vignae Semen), 비올래 허바(Violae Herba), 비스시 허바(Visci Herba), 비텍스 오일(Vitex Oil), 비티시스 프룩투스(Viticis Fructus), 비티시스 네군도 폴륨(Viticis Negundo Folium), 발디미리애 라딕스(Vladimiriae Radix), 위핑 포르스티아 추출물(Weeping Forsythia Extract), 웬유진 리히조마 콘시숨(Wenyujin Rhizoma Concisum), 잔티 프룩투스(Xanthii Fructus), 잔토옥실리 퍼리카르피움(Zanthoxyli Pericarpium), 잔토옥실리 라딕스(Zanthoxyli Radix), 자오시스(Zaocys), 제도아리 투르메릭 오일(Zedoary Turmeric Oil), 진지베리스 리히조마 프래파라텀(Zingiberis Rhizoma Praeparatum), 진지베리스 리히조마 리센스(Zingiberis Rhizoma Recens), 진지베리스 리히조마(Zingiberis Rhizoma), 지지피 스피노새 지멘(Ziziphi Spinosae Semen)로 이루어진 그룹으로부터 선택된다.
특정 실시태양에서, 약물 내용물은 매질을 추가로 포함한다. 매질은 API와 결합될 수 있으며, 즉 매질은 API와 물리적으로 접촉하고 있다. 특정 실시태양에서, API는 매질에 삽입된다. 특정 실시태양에서, API는 매질 내에 분산되어있다. 특정 실시태양에서, 매질은 본 발명에 개시된 바와 같은 열가소성 재료로 제조된다.
특정 실시태양에서, 매질은 코코아 버터, 폴리에틸렌 글리콜(PEG), 수크로오스, 글루코오스, 갈락토오스, 프룩토오스, 자일로오스락토오스, 말토오스, 트레할로오스, 소르비톨, 만니톨, 말토덱스트린, 라피노오스, 스타키오스, 프룩토올리고사카라이드 및 이들의 조합을 포함한다. 특정 실시태양에서, 기질은 가소제를 추가로 포함한다.
약물 내용물은 구획 내로 적재될 임의의 적합한 형상 및 크기일 수 있다.
특정 실시태양에서, 약물 내용물은 공유 결합, 비공유 상호 작용 또는 링커를 통해 구획에 작동 가능하게 연결된다. 따라서, 약물 내용물 및 기질은 별도로 제조될 수 있고 공유 결합 또는 비공유 상호 작용을 통해 함께 결합될 수 있다. 특정 실시태양에서, 제형은 3D 인쇄 방법을 사용하여 단일 공정으로 약물 내용물 및 기질을 생산함으로써 제조된다.
특정 실시태양에서, 약물 내용물은 압축된 정제, 타원형 정제, 환제 또는 캡슐 형태로 형성된다. 특정 실시태양에서, 약물 내용물의 형태는 구획의 형태와 일치한다. 예를 들어 구획이 원형인 경우, 약물 내용물은 또한 구획을 채우기 위해 원형이다.
특정 실시태양에서, 약물 내용물은 도 6에 예시된 바와 같이 나노입자의 형태이다. 약물 내용물은 API가 용해되거나 현탁된 용액과 혼합될 수 있다. 그런 후에, 용액은 제형의 3차원 인쇄 과정 동안 인쇄 층의 꼭대기에 안개 모양이 되고/분무된다. 일단 약물 내용물을 함유하는 용액이 건조되면, 약물 내용물이 제형에 분산된다. 나노입자는 넓은 표면적을 가지며 높은 용해 속도를 가질 것이다.
나노입자의 크기는 1 nm 내지 900 nm 범위(바람직하게는 100-800nm, 100-700nm, 100-600nm, 100-500nm, 100-400nm, 100-300nm, 100-200nm, 1nm, 2nm, 3nm, 4nm, 5nm, 6nm, 7nm, 8nm, 9nm, 10nm, 11nm, 12nm, 13nm, 14nm, 15nm, 16 20nm, 100nm, 200nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm 크기)일 수 있다. 나노입자의 크기는 적절한 합성 방법 및/또는 시스템을 선택함으로써 조절할 수 있다. 원하는 크기 범위 내에서 나노 입자를 얻기 위해, 합성 조건은 예를 들어 원하는 용액 농도 또는 원하는 공동 범위를 제공하도록 적절히 제어되거나 변화될 수 있다(상세한 리뷰는 예를 들어, Vincenzo Liveri, Controlled synthesis of nanoparticles in microheterogeneous systems, Published by Springer, 2006에서 발견할 수 있다).
특정 실시태양에서, 약물 내용물은 도 7에 예시된 바와 같이 미세바늘 형태이다. 미세바늘은 제형의 3차원 인쇄 동안 제형과 함께 인쇄되거나 제형 속에 삽입될 것이다. 미세바늘은 사카라이드, PLGA 폴리머 또는 API 또는 이의 조합으로 구성될 수 있다. 미세바늘은 비경구 또는 장용성으로 투여될 때 환자의 순환계로의 API 침투를 보조할 수 있다.
특정 실시태양에서, 약물 내용물은 네트워크를 형성한다. 도 8a에 도시된 바와 같이, 제형은 약물 내용물이 적재된 구획을 형성하는 기질을 갖는다. 약물 내용물은 네트워크를 형성하는 기질을 갖는다. 정제의 틀 구조는 1-10분 사이에 용해되는 재료로 제조되며, 기질은 2-60초, 바람직하게는 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60초 후에 용해된다. 도 8b에 도시된 바와 같이, API는 제형이 투여된 후 수초 후에 방출될 수 있다.
약물 내용물 융합 증착 모델링(FDM)과 같은 부가적인 방법을 사용하여 제조될 수 있다. 특정 실시태양에서, 약물 내용물은 API 및 부형제의 혼합물을 압출하도록 구성된 3차원 프린터(3D 프린터)를 사용하여 제조될 수 있다. API는 압출되기 전에 용융되어 용융된 기질과 균질하게 혼합될 수 있다. 대안적으로, 고체 형태의 API(예를 들어, 분말)는 압출되기 전에 용융된 기질과 혼합되어 분산될 수 있다. 일반적으로, 압출 공정은 기질의 유리 전이 온도(Tg)보다 10°내지 40℃ 높은 온도 및 API의 융점에 가까운 온도에서 수행될 수 있다. 3차원 프린터에서 사용하기에 적합한 온도가 되면, 기질은 3 차원 인쇄 표면에 증착될 수 있다. 약물 내용물의 모양과 크기는 3차원 인쇄 과정을 프로그래밍하여 제어될 수 있다. 특정 실시태양에서, 약물 내용물은 기질의 동일한 공정에서 제조된다. 특정 실시태양에서, 약물 내용물은 기질의 제조 전에 제조되고 기질이 제조되는 동안 또는 후에 구획에 적재된다.
특정 실시태양에서, 약물 내용물이 구획에 적재될 때, 구획과 결합되어, 예를 들어 기질에 삽입되거나 고정된다. 특정 실시태양에서, 약물 내용물은 구획 내로 적재될 때 기질로부터 분리가능하다.
D. 제어 방출
본 발명에 개시된 제형은 경구 투여 후에 다양한 방출 프로파일을 제공할 수 있다. 특정 실시태양에서, 투여 형은 일정한 방출 프로파일, 박동성 또는 지연된 전달 또는 비선형 약물 방출을 제공한다. 특정 실시태양에서, 제형은 0차 방출 동역학을 제공한다.
적절한 방출 프로파일은 특정 약물 요법에 이점을 제공할 수 있다. 예를 들어, 박동성 방출 프로파일은 피크 관통율의 결과적인 감소에 의한 조절된 흡수, 위장관 내 특정 영역에 대한 약물의 표적 방출 및 급식 상태와 무관한 흡수를 제공하여 내성을 예방하고, 부작용을 줄이고 환자의 순응도를 향상시키며, 이는 ADHD와 같은 질병을 치료하는데 바람직하다. 또 다른 예로서, 적재 투여량 후 유지 투여량에 의한 방출 프로파일은 고혈압 및 당뇨병과 같은 만성 질환을 치료하는데 효과적일 수 있다.
본 발명에 개시된 투여량을 사용하여 방출 프로파일을 조절하는 메카니즘의 일부가 위에서 논의되었다. 예를 들어, 시간이 지남에 따라 끊임없이 침식되는 기질의 노출된 표면 영역을 조작함으로써, 기질에 삽입된 약물 내용물은 시간이 지남에 따라 일정량의 약물을 전달할 수 있다. 또한, 방출 프로파일은 구획 개구부의 크기 및/또는 구획의 기하학적 형상에 의해 제어될 수 있다.
특정 실시태양에서, 방출 프로파일은 플러그에 의해 밀봉되거나 차단되는 구멍을 갖는 구획의 디자인에 의해 제어될 수 있다. 플러그는 제형이 위장관을 통과할 때 마멸될 수 있는 수용성, 다공성 또는 침식성 재료 또는 pH 민감성 재료 또는 소수성 재료로 제조된다. 제형이 대상에게 투여될 때, 플러그는 용해, 침투 또는 침식되어, 구획으로부터 약물 내용물을 방출한다. 약물 내용물의 방출 프로파일은 적절한 침식/용해 속도 또는 침투 속도의 플러그를 선택하여 제어될 수 있다. 대안 적으로, 약물 내용물의 방출 프로파일은 플러그의 형상 및/또는 크기(예컨대, 적절한 길이의 막대 형상)를 사용하여 제어될 수 있다. 방출 프로파일은 구획의 수로 제어될 수도 있다. 도 9는 제형의 양 측면 상에 존재하는 복수의 컬럼형 구획을 형성하는 기질을 갖는 예시적인 제형을 도시한다. 각 구획에 약물 내용물이 적재된다. 각 구획은 막대 모양의 플러그로 막힌 구멍을 갖는다. 플러그는 상이한 용해 속도를 가진다. 플러그의 크기, 모양 및 용해 속도에 따라, API는 지속적, 계속, 동시, 연속 또는 맥동 방식으로 방출될 수 있다.
도 10a는 연속적인 방출 프로파일을 제공하는 예시적인 제형을 도시한다. 도 10a를 참조하면, 제형(700)은 3개의 컬럼 형상 구획(702~704)을 형성하는 기질(701)을 갖는다. 각 구획에 동일한 API의 약물 내용물이 적재된다. 각 구획은 막대 모양의 플러그(705~707)로 막혀있는 구멍을 갖는다. 플러그는 동일한 재료로 제조되지만 길이가 다르다. 결과적으로, 플러그를 분해하고 구획을 개방하여 약물 내용물을 방출하는데에는 상이한 시간이 걸린다. 도 10c에 예시된 바와 같이, 가장 짧은 플러그가 먼저 용해되어, 제 1 구획으로부터 API를 방출한다. 제 1 구획의 API가 완전히 방출되면, 중간 길이의 플러그가 용해되어 제 2 구획으로부터 API를 방출한다. 제 2 구획의 API가 완전히 방출되면, 세 번째 플러그가 용해되어 제 3 구획으로부터 API를 방출한다. 결과적으로, 혈장 약물 수준은 제 1 구획의 약물 내용물이 방출될 때 제 1 피크에 도달한다. 제 1 구획으로부터 방출된 API가 제거되기 시작하면, 혈장 약물 농도가 감소되기 시작한다(도 10d 참조). 혈장 약물 수준이 임계 수준(약물이 효과가 없을 수 있는 수평선) 아래로 떨어지기 전에, 제 2 구획의 API가 방출되고 혈장 약물 수준이 다시 증가한다. 제 2 구획으로부터 방출된 API가 제 2 피크에 도달하여 제거되기 시작하면, 제 3 구획의 플러그가 용해되어 구획을 개방한다. 결과적으로, 혈장 API 수준은 장기간에 걸쳐 임계적 수준 이상으로 유지되어 특정 질병에 도움이 된다.
연속 방출 방식은 또한 도 10b에 예시된 바와 같이 층의 형태로 포장된 몇몇 약물 내용물을 갖는 다른 예시적인 제형을 통해 달성될 수 있다. API는 도 10c에 도시된 바와 같이 API의 연속적이고 지속적인 방출을 제공하기 위해 동기식으로 각각의 층을 용해시킴으로써 지속적인 방식으로 방출될 수 있다. 특정 실시태양에서, 제형의 외층은 제형이 투여될 때 즉시 용해되고 삽입된 약물 내용물을 방출한다. 그러나 중간에 끼인 층은 외층이 환경과의 계면을 차단하기 때문에 용해되지 않거나 훨씬 느리게 용해된다. 외층의 용해는 중간에 끼인 층을 노출시키고 그 용해를 촉진시켜, 도 10c에 예시된 바와 같은 연속적인 방출 프로파일을 제공한다.
특정 실시태양에서, 제형은 제 1 구획 내에 적재된 가스 생성 구성요소를 포함한다. 특정 실시태양에서, 가스 생성 구성요소는 유기산 및 탄산염, 아황산염, 중탄산염, 탄산나트륨, 중탄산나트륨, 메타이아황산나트륨, 탄산칼슘 및 이의 조합으로 이루어진 그룹으로부터 선택되며, 이들은 위액과 접촉하여 이산화탄소 또는 이산화황 가스를 배출한다. 기질이 위장에서 용해, 침투 또는 침식될 때, 가스 생성 구성요소는 산 환경에 노출되거나 물이 구획 속에 침투되어 산과 중탄산 나트륨 사이의 반응을 유도하고 가스를 생성하여 발포 방식으로 약물 내용물을 방출한다.
본 발명에 개시된 제형은 적어도 부분적으로 지연 방출 형태인 하나 이상의 약물 내용물을 포함할 수 있으며, 지연 방출은 예를 들어 당업자에게 공지된 통상적인 재료 및 예를 들어, API를 지연 방출 기질/기질에 삽입하거나 또는 하나 이상의 지연 방출 코팅을 도포하는 방법의 도움으로 달성될 수 있다. 지연 방출을 통해, API 방출은 제형의 1일 2회 또는 1회 투여가 충분하도록 조절될 수 있으며, 이는 특히 통증을 퇴치하기 위해, 예를 들어 지속된 수준의 활성 화합물이 필요한 경우에 유리하다.
특정 실시태양에서, 제형은 구강에서 활성 성분을 즉시 방출한다. 한 예는 구강에 제공되거나 설하 영역을 차지하는 것이다.
특정 실시태양에서, 제형은 바람직하게는 글리세릴 모노스테아레이트, 반-합성 트라이글리세라이드 유도체, 반-합성 글리세라이드, 경화 피마자유, 글리세릴 팔미토스테아 레이트, 글리세릴 베헤네이트, 폴리바이닐피롤리돈, 젤라틴, 스테아린산 마그네슘, 스테아르산, 스테아린산 나트륨, 활석, 소듐 벤조에이트, 붕산 및 콜로이드성 실리카, 지방산, 치환 트라이글리세라이드, 글리세라이드, 폴리옥시알킬렌 글리콜 및 이의 유도체로 이루어진 그룹으로부터 선택된 당업자에게 공지된 통상적인 보조 물질을 추가로 포함할 수 있다.
제형의 제조
본 발명에 개시된 방출 제어 제형은 임의의 적절한 방법을 사용하여 제조될 수 있다. 특정 실시태양에서, 제형은 3차원 인쇄(3D 인쇄)를 사용하여 생산된다.
본 발명에 사용된 바와 같이, 3D 인쇄는 디지털 디자인으로부터 층별로 3D 물체를 생산하는 과정을 의미한다. 3D 인쇄의 기본 과정은 U.S. Pat. Nos. 5,204,055; 5,260,009; 5,340,656; 5,387,380; 5,503,785; 및 5,633,021에 기술되어 있다. 3D 인쇄와 관련된 추가 미국 특허 및 출원은 U.S. Pat. Nos. 5,490,962; 5,518,690; 5,869,170; 6,530,958; 6,280,771; 6,514,518; 6,471,992; 8,828,411; U.S. PG Pub. Nos: 2002/0015728; 002/0106412; 2003/0143268; 2003/0198677; 2004/0005360을 포함한다. 3D의 상세한 설명에 대해 상기 특허 및 출원을 참조할 수 있다.
원료, 장비 및 응고 측면에서 제형 제조를 위한 상이한 3D 인쇄 방법이 개발되었다. 이런 3D 인쇄 방법은 접합제 증착(L Gibson et al. (2015) Additive Manufacring Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing. 2 ed. Springer, New York; W.E. Katstra et al. (2000) Oral dosage forms fabricated by three dimensional printing, J. Control Release 66: 1-9; W.E. Katstra et al. (2001) Fabrication of complex oral delivery forms by three dimensional printing, Dissertation in Materials Science and Engineering, Massachussetts Institute of Technology; H. Lipson et al. (2013) Fabricated: The New World of 3D printing, John Wiley & Sons, Inc.; G. Jonathan, A. Karim (2016) 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems, Int. J. Pharm. 499: 376-394 참조), 재료 분사(G. Jonathan, A. Karim (2016) 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems, Int. J. Pharm. 499: 376-394 참조), 압출(L Gibson et al. (2015) Additive Manufacring Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing. 2 ed. Springer, New York 참조) 및 광중합(F.P. Melchels et al. (2010) A review on stereolithography and its application in biomedical engineering. Biomaterials 31: 6121-30 참조)을 포함한다.
특정 실시태양에서, 본 발명에 개시된 제형은 압출 방법을 사용하여 제조된다. 압출 공정에서, 재료는 로봇 작동식 노즐로부터 압출된다. 분말층이 필요한 접합제 증착과 달리, 압출 방법은 모든 기질 상에 인쇄할 수 있다. 본 발명에 개시된 열가소성 재료, 페이스트 및 콜로이드 현탁액, 실리콘 및 다른 반고체를 포함하는 다양한 재료가 3D 인쇄를 위해 압출될 수 있다. 압출 인쇄의 한 일반적인 유형은 인쇄를 위해 견고한 폴리머 필라멘트를 사용하는 융합 증착 모델링이다. 융착 모델링에서, 기어 시스템은 필라멘트를 압출을 위한 가열된 노즐 어셈블리 속으로 구동한다(L Gibson et al. (2015) Additive Manfacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing. 2 ed. Springer, New York 참조).
인쇄 작업에 대한 제조 지시는 직접 코딩, 견고한 CAD 모델로부터의 도출 또는 3D 인쇄 기계의 컴퓨터 인터페이스 및 애플리케이션 소프트웨어에 특정한 다른 수단을 포함하는 다양한 방법으로 생성될 수 있다. 이런 지시는 방울의 수와 공간 배치 및 각 선형 치수 (X, Y, Z)에서의 방울 간격 및 방울 당 유체의 부피 또는 질량과 같은 일반적인 인쇄 매개변수에 대한 정보가 포함할 수 있다. 소정의 재료 세트의 경우, 이런 매개변수는 생성된 구조의 품질을 개선하기 위해 조절될 수 있다. 생성된 구조의 전체 해상도는 분말 입자 크기, 유체 방울 크기, 인쇄 매개변수 및 재료 특성의 함수이다.
다양한 범위의 약학적 재료를 취급할 수 있고 조성물 및 구조를 국소적으로 제어할 수 있기 때문에, 3D 인쇄는 본 발명에 따른 복잡한 기하학적 구조 및 조성물을 갖는 제형의 제작에 매우 적합하다.
3D 인쇄 방법을 사용하여 제형을 제조하는 것은 또한 개인화된 의학을 용이하게 한다. 개인화된 의학은 치료 결정 및 개인화된 제형 형태 디자인을 돕기 위해 바이오마커에 기초한 환자 집단의 계층화를 의미한다. 물리적 디자인을 수정하는 것보다 디지털 디자인을 수정하는 것이 더 쉽다. 또한 자동화된 소규모 3D 인쇄는 운영 비용이 거의 들지 않을 수 있다. 따라서, 3D 인쇄는 여러 개의 작고 개별화 된 배치를 경제적으로 실현할 수 있으며 순응도를 높이기 위해 디자인된 개인화된 제형을 가능하게 한다.
개인화된 제형은 환자의 체중 및 신진대사에 기초하여 전달된 약물의 양을 조절할 수 있게 한다. 3D 인쇄된 제형은 성장하는 어린이에게 정확한 투약을 보장하고 고효능 약물의 개인화된 투약을 허용할 수 있다. 개인화된 제형은 모든 환자의 투약을 단일 일일 투여량으로 결합하여 투약에 대한 환자의 순응도를 향상시킬 수 있다.
도 11은 개인화된 제형을 제조하기 위해 3D 인쇄를 사용하는 공정을 예시한다. 각 환자마다, 체중, 연령, 신진대사 지표 및 게놈 바이오 마커 등 다양한 임상 테스트 결과를 얻을 수 있다. 임상 테스트 결과는 컴퓨터 소프트웨어에 입력된다. 이 정보는 의사와 약동학 모델의 처방과 결합되어 특정 투여량과 약물 조합의 제형을 디자인한다. 그런 다음 지시가 3D 프린터로 전송되어 디자인된 제형을 제조하여 환자에게 투여한다.
다수 약물의 제어된 방출
본 발명에 개시된 제형 및 방법은 특정 치료법에서 약물 조합을 최적화하기 위해 둘 이상의 약물의 방출을 제어하는데 사용될 수 있다. 예를 들어, 고콜레스테롤혈증을 치료하는 정제는 아토르바스타틴 칼슘의 즉시 방출 및 니코틴산의 연장 방출을 제공하도록 디자인될 수 있다. 다른 예에서, 진통을 위한 비 스테로이드성 소염 진통제(NSAID)는 NSAID 유발 점막 손상을 예방하기 위해 NSAID의 지속적인 방출 및 H2-수용체 길항제의 신속 방출을 제공하도록 디자인될 수 있다.
특정 실시태양에서, 기질은 다수의 구획을 형성하고, 각각은 약물 내용물이 적재된다. 특정 실시태양에서, 다수의 구획은 연결된다. 특정 실시태양에서, 다수의 구획은 분리된다. 특정 실시태양에서, 상이한 구획 속에 적재된 약물 내용물은 동일하다. 특정 실시태양에서, 상이한 구획 속에 적재된 약물 내용물은 상이하다. 제형은 시너지 치료 효과를 발휘하기 위해 다수의 약물 내용물의 동시 또는 순차적 방출을 제공하도록 디자인될 수 있다.
도 12a는 API를 동시에 방출할 수 있는 예시적인 제형을 도시한다. 도 12a를 참조하면, 제형(800)은 3개의 적층된 층(801~803)을 포함하며, 각각은 상이한 약물 내용물이 삽입되어 있다. 도 12b에 예시된 바와 같이, 제형(800)이 투여될 때, 약물 내용물은 층이 용해될 때 동시에 방출되지만 상이한 속도로 방출된다.
도 13a는 동시 방출 프로파일의 또 다른 예시적인 제형 나타낸다. 도 13a를 참조하면, 제형(900)은 3개 약물 내용물이 적재되는 3개의 컬럼형 구획(901~903)을 포함한다. 각각의 약물 내용물은 상이한 용해 속도의 기질에 삽입된 API를 함유한다. 도 13b에 예시된 바와 같이, 제형(900)이 투여 될 때, 3개 API는 약물 내용물의 기질이 용해될 때 동시에 방출되지만 상이한 속도로 방출된다. API의 방출 속도는 구획의 형태 또는 구획의 개구부의 크기에 의해 제어될 수 있다.
도 14a 및 14b는 3개 API의 동시 방출 프로파일의 추가적인 예시적인 제형을 나타낸다. 도 14a를 참조하면, 제형(1000)은 약물 내용물이 삽입된 3개의 원형 세그먼트(1001~1003)를 포함한다. 도 14c에 예시된 바와 같이, 세그먼트가 용해될 때 약물 내용물은 동시에 방출되고, 약물 내용물의 방출 속도는 세그먼트의 용해 속도에 의해 제어될 수 있다. 도 14b를 참조하면, 제형(1100)은 세그먼트보다 느리게 용해되는 쉘(1104)에 의해 감싸인 3개의 원형 세그먼트(1101~1103)를 포함한다. 세그먼트에 삽입된 약물 내용물의 방출 속도는 쉘(1104)이 환경과 세그먼트(1101~1103)의 경계면을 차단하기 때문에 감소된다.
도 15a는 2개의 API의 순차적 방출 프로파일의 예시적인 제형을 도시한다. 도 15a를 참조하면, 제형(1200)은 약물 내용물(1202)이 채워지는 구획을 형성하는 기질(1201)을 포함한다. 기질(1201)은 제 1 API를 함유하고, 약물 내용물(1202)은 제 2 API를 함유한다. 도 15b에 예시된 바와 같이, 제형이 투여 될 때 기질이 용해됨에 따라 제 1 API가 방출된다. 제 2 API는 기질이 용해되어 약물 내용물을 노출시킬 때까지 방출되지 않고, API의 순차적 방출 프로파일을 제공한다.
도 16a는 순차적 방출 프로파일의 또 다른 예시적인 제형 도시한다. 도 16a를 참조하면, 제형(1300)은 3개의 약물 내용물이 적재된 3개의 컬럼형 구획(1302~1304)을 형성하는 기질(1301)을 갖는다. 구획(1302~1304)은 상이한 길이 및/또는 용해 속도를 갖는 막대형 플러그에 의해 차단되는 구멍을 갖는다. 도 16b에 예시된 바와 같이, API는 구획을 개방하기 위해 플러그가 순차적으로 용해될 때 순차적인 방식으로 방출된다.
도 17a는 동시 방출 프로파일 또는 순차적 방출 프로파일을 갖는 예시적인 제형을 도시한다. 도 17a를 참조하면, 제형(1400)은 상이한 용해 속도를 갖는 4개의 세그먼트(1701~1704)를 포함하는 기질을 갖는다. 특정 실시태양에서, 도 17b에 예시된 바와 같이, 약물 내용물은 세그먼트(1701~1704)에 삽입되어 기질이 용해될 때 동시에 방출된다. 특정 실시태양에서, 각 세그먼트는 약물 내용물이 적재되는 구획을 함유한다. 도 17c에 예시된 바와 같이, 약물 내용물은 기질이 용해될 때 순차적으로 방출된다.
실시예 1
이 실시예는 제어된 방출 프로파일을 갖는 제형의 디자인을 예시한다.
도 18에 도시된 바와 같이, 제형은 원형 구획을 형성하는 편평한 정제 기질을 포함하였다. 기질은 PEG8000으로 제조하였다. 벤조산은 모듈 약물 내용물로 사용하였다.
제형으로부터 벤조산의 방출 프로파일을 하기 방법으로 측정하였다. pH 8의 Na2HPO4 용액을 벤조산의 용해제로 제조하였다. 120μg/mL의 벤조산 용액을 30μg/mL, 15μg/m, 7.5μg/m, 3.75μg/mL 및 1.875μg/mL 용액으로 연속 희석하였고, 이의 226nm에서의 흡광도를 UV 분광 광도계를 사용하여 측정하였다. 얻은 수치를 선형 회귀법으로 처리하여 식 y = 0.0599x + 0.0347을 갖는 벤조산 농도의 표준 곡선을 생성하였다. 벤조산의 방출량을 측정하기 위해, 제형을 37℃±0.5℃의 탈기 된 pH 8 Na2HPO4 용액에 용해시키고 100rpm에서 원심분리하였다. 5 mL 용액을 각 시점에서 용액으로부터 수집하여 벤조산의 농도를 측정하였고 5 mL의 용해제를 용액에 다시 첨가하였다. 수집된 용액을 0.45um 막을 통해 여과한 후 UV 분광 광도계로 옮겨 226 nm에서의 흡광도를 측정하였다. 방출된 벤조산의 백분율은 하기 식을 사용하여 계산하였다:
여기서 C n은 측정된 농도를 의미하고, V t는 총 용액 부피를 의미하고, V s는 시료의 양을 의미하고, Q 벤조산은 제형에서 벤조산의 양을 의미한다.
PEG8000의 방출은 하기 방법을 사용하여 측정한다. PEG8000의 표준 곡선을 제조하기 위해, 0.1275g PEG8000 표준 샘플을 25 mL 부피 플라스크의 물에 용해시켰다. 각각 1 mL, 2 mL, 5 mL 및 10 mL를 10 mL 메스 플라스크에 옮기고 물에 희석하여 대조액을 만든다. 50ul의 대조액을 액체 크로마토그래피(3개의 Waters UltrahydrogelTM 120/250/500 시리즈 연결, 유속 0.5 ml/min, 40℃ 온도, 차동 굴절 검출기로 측정)에 주입하였다. 부피의 면적을 측정하여 y 축으로 사용하였다. 대조액 농도의 로그 숫자를 x 축으로 사용하였다. PEG8000의 표준 곡선은 y = 1.024x + 8.918의 식으로 생성하였다. 방출된 PEG8000의 백분율은 다음 식을 사용하여 계산하였다:
여기서 C n은 측정된 농도를 의미하고,
V t는 용액 부피를 의미하고 V s는 시료의 부피를 의미하고,
Q PEG8000은 제형에서 PEG8000의 양을 의미한다.
결과: 도 18c에 예시된 바와 같이, 벤조산의 방출 프로파일은 D. Brooke and R. J. Washkuhn (Zero-Order Drug Delivery System: Theory and Preliminary Testing, J Pharm Sci., 1977, 66: 159-162)에 따른 모델 프로파일과 일치하고, 경계면에 의해 제어되었다. 따라서, 제어된 방출 프로파일은 본 발명에 개시된 제형에 따라 디자인될 수 있다.
실시예 2
이 실시예는 상이한 구획으로부터의 약물 내용물의 방출을 제어하는 제형의 디자인을 예시한다.
제형 디자인: 2개 제형을 융합 모델링 방법을 이용하여 생산하였다. 제형의 기질은 코포비돈(Kollidon® VA64) 72%, PEG1500 18% 및 Soluplus® 10%로 제조하였다. 약물 내용물은 목시플록사신 하이드로클로라이드 30%, PEG1000 70%로 구성되었다. 제형의 개략도가 도 19a 및 19b에 예시된다. 도 19a 및 19b를 참조하면, 제형(1600)은 2개의 구획(1602 및 1603)을 형성하는 기질(1601)을 포함하였다. 구획은 각각 벽(1604 및 1605)에 의해 둘러싸여있다. 제 1 제형의 경우, 두 구획은 각각 0.75mm 및 1.5mm의 두께를 갖는 벽으로 둘러싸여있다. 제 2 제형의 경우, 두 구획은 각각 0.75mm 및 2.25mm의 두께를 갖는 벽으로 둘러싸여있다.
약물 내용물의 방출을 검출하기 위해, 제형을 100rpm에서 pH 6.8의 인산염 완충액 900 ml에 첨가하였다. 완충액의 UV 흡수를 분석하여 약물 내용물의 방출을 측정하였다.
방출 분석의 결과를 도 19c 및 19d에 예시하였다. 도 19c에 도시된 바와 같이, 제 1 제형이 완충액에 20분 동안 첨가될 때, 제 1 구획이 개방되고, 제 1 구획의 약물 내용물이 방출되었다. 제 2 구획은 제형이 완충액에 첨가된 후 40분까지 개방되지 않았다. 결과가 도 19d에 예시된 제 2 제형의 경우, 제 2 구획은 제형이 완충액에 첨가된 후 60분까지 개방되지 않았다. 따라서, 제형의 방출 프로파일은 구획을 둘러싸는 벽의 두께를 통해 제어될 수 있다.
본 발명의 원리가 특정 실시예와 관련하여 기술되었지만, 이들 설명은 단지 예로서 이루어지며 본 발명의 범위를 제한하려는 의도는 아니라는 것을 명확히 이해해야한다. 본 발명에 개시된 내용은 예시 및 설명을 위해 제공되었다. 기술된 정확한 형태에 대해 개시된 것을 포괄하거나 제한하는 것으로 의도되지 않는다. 많은 수정 및 변형이 당업자에게 명백할 것이다. 개시된 내용은 설명된 기술 분야의 개시된 실시태양의 원리 및 실제 적용을 가장 잘 설명하도록 선택되고 기술되어, 당업자가 고려된 특정 용도에 적합한 다양한 실시태양 및 다양한 변형을 이해할 수 있게 한다. 개시된 내용의 범위는 다음 청구범위 및 이의 등가물에 의해 한정되는 것으로 의도된다.
[표 1]
Claims (52)
- 구획을 형성하는 기질; 및
구획 속에 적재된 약물 내용물을 포함하는 제형. - 제 1 항에 있어서,
약물 내용물은 기질에 작동 가능하게 연결되는 제형. - 제 1 항에 있어서,
약물 내용물은 기질로부터 분리되는 제형. - 제 1 항에 있어서,
기질은 적어도 하나의 열가소성 재료로 제조되는 제형. - 제 4 항에 있어서,
열가소성 재료는 친수성 폴리머, 소수성 폴리머, 팽창성 폴리머, 비 팽창성 폴리머, 다공성 폴리머, 비 다공성 폴리머, 침식성 폴리머, 비 침식성 폴리머로 이루어진 그룹으로부터 선택되는 제형. - 제 4 항에 있어서,
열가소성 재료는 폴리바이닐 카프로락탐-폴리바이닐 아세테이트-폴리에틸렌 글리콜 그래프트 코폴리머 57/30/13, 폴리바이닐피롤리돈-코-바이닐-아세테이트 (PVP-VA), 폴리바이닐피롤리돈-폴리바이닐 아세테이트 코폴리머(PVP-VA) 60/40, 폴리바이닐피롤리돈(PVA), 폴리바이닐 아세테이트(PVAc) 및 폴리바이닐 피롤리돈(PVA) 80/20, 폴리에틸렌 글리콜-폴리바이닐 알코올 그래프트 코폴리머 25/75, 콜리코트 IR-폴리바이닐 알코올 60/40, 폴리바이닐 알코올(PVA 또는 PV-OH), 폴리(바이닐 아세테이트)(PVAc), 폴리(부틸 메타크릴레이트-코-(2-다이메틸아미노에틸)메타크릴레이트-코-메틸 메타크릴레이트) 1:2:1, 폴리(다이메틸아미노에틸메타크릴 레이트-코-메타크릴 에스터), 폴리(에틸 아크릴레이트-코-메틸 메타크릴레이트-코-트라이메틸아모니오에틸 메타크릴레이트 클로라이드), 폴리(메틸 아크릴레이트-코-메틸 메타크릴레이트-코-메타크릴산) 7:3:1, 폴리(메타크릴산-코-메틸메타크릴레이트) 1:2, 폴리(메타크릴산-코-에틸 아크릴레이트) 1:1, 폴리(메타크릴산-코-메틸 메타크릴레이트) 1:1, 폴리(에틸렌 옥사이드)(PEO), 폴리(에틸렌 글리콜)(PEG), 다분기 폴리에스터아마이드, 하이드록시프로필 메틸셀룰로오스 프탈레이트, 하이프로멜로오스 프탈레이트, 하이드록시프로필 메틸셀룰로오스 또는 하이프로멜로오스(HMPC), 하이드록시프로필 메틸셀룰로오스 아세테이트 숙시네이트 또는 하이프로멜로오스 아세테이트 숙시네이트(HPMCAS), 폴리(락티드-코-글리콜라이드)(PLGA), 카보머, 폴리(에틸렌-코-바이닐 아세테이트), 에틸렌-바이닐 아세테이트 코폴리머, 폴리에틸렌(PE) 및 폴리카프로락톤(PCL), 하이드록시 프로필 셀룰로오스(HPC), 폴리옥실 40 수소화 캐스터유, 메틸 셀룰로오스(MC), 에틸 셀룰로오스(EC), 폴록사머, 하이드록시프로필 메틸셀룰로오스 프탈레이트(HPMCP), 폴록사머, 수소화 캐스터유 및 대두유, 글리세릴 팔미토스테아레이트, 카나우바 왁스, 폴리락트산(PLA), 폴리글리콜산(PGA), 셀룰로오스 아세테이트 부티레이트(CAB), 콜로이드성 실리콘, 이산화물, 수크로오스, 글루코오스, 폴리바이닐 아세테이트 프탈레이트(PVAP) 및 이의 조합으로 이루어진 그룹으로부터 선택되는 제형. - 제 1 항에 있어서,
구획은 원형, 원뿔형, 피라미드형, 원통형, 입방체형 또는 직육면체형, 삼각형 또는 다각형 프리즘형, 사면체형 및 이의 조합으로 이루어진 그룹으로부터 선택되는 형상을 갖는 제형. - 제 1 항에 있어서,
약물 내용물은 나노입자 형태인 제형. - 제 1 항에 있어서,
약물 내용물은 미세바늘 형태인 제형. - 제 1 항에 있어서,
약물 내용물은 네트워크 구조 또는 다공성 구조를 형성하는 제형. - 제 1 항에 있어서,
약물 내용물은 활성 약학적 성분(API)을 포함하는 제형. - 제 11 항에 있어서,
API는 국소 마취제, 통증 관리제, 수면 장애제, 항간질제 및 항경련제, 항알츠하이머제, 진통제, 항통풍제, 항고혈압제, 항부정맥제, 이뇨제, 간 질환 치료제, 췌장 질환 치료제, GI 질환 치료제, CNS 질환 치료제, 항히스타민제, 항알레르기제, 글루코코르티코이드제, 호르몬제 및 피임약, 혈당 강하제, 항골다공증제, 항생제, 설폰아마이드, 퀴놀론 및 기타 합성 항균제, 항 결핵제, 항바이러스제, 항염증제, 항종양제, 면역 조절제, 수의사 약물, 미용 활성제, 전통 중국 의약 및 전통 중국 의약의 추출물로 이루어진 그룹으로부터 선택되는 제형. - 제 11 항에 있어서,
약물 내용물은 API보다 높은 침식/용해 속도를 갖는 매질을 포함하는 제형. - 제 11 항에 있어서,
약물 내용물은 적어도 하나의 부형제를 추가로 포함하는 제형. - 제 14 항에 있어서,
부형제는 코코아 버터, 폴리에틸렌 글리콜(PEG), 수크로오스, 글루코오스, 갈락토오스, 프룩토오스, 자일로스락토오스, 말토오스, 트레할로스, 소르비톨, 만니톨, 말토덱스트린, 라피노오스, 스타키로오스, 프룩토-올리고사카라이드 및 이의 조합으로 이루어진 그룹으로부터 선택된 수용성 재료로 제조되는 제형. - 제 1 항에 있어서,
구획은 플러그에 의해 차단되는 구멍을 갖는 제형. - 제 16 항에 있어서,
플러그는 수용성 폴리머, 침식성 폴리머 또는 용해성 폴리머, 왁스 유사 재료 또는 사카라이드 또는 이의 조합으로 이루어진 그룹으로부터 선택된 재료로 제조되는 제형. - 제 1 항에 있어서,
제 1 구획 내에 적재된 가스 생성 구성요소를 추가로 포함하는 제형. - 제 17 항에 있어서,
가스 생성 구성요소는 수용성 탄산염, 아황산염, 중탄산염, 탄산나트륨, 중탄산나트륨, 메타이아황산나트륨, 탄산칼슘 및 이의 조합으로 이루어진 그룹으로부터 선택되며, 이들은 위액과 접촉하여 이산화탄소 또는 이산화황 가스를 배출하는 제형. - 적어도 제 1 구획 및 제 2 구획을 형성하는 기질; 및
제 1 구획 내에 적재된 제 1 약물 내용물 및 제 2 구획 내에 적재된 제 2 약물 내용물을 포함하는 제형. - 제 20 항에 있어서,
제 1 구획과 제 2 구획은 연결되는 제형. - 제 20 항에 있어서,
제 1 구획과 제 2 구획은 분리되는 제형. - 제 20 항에 있어서,
제 1 약물 내용물은 제 2 약물 내용물과 동일한 제형. - 제 20 항에 있어서,
제 1 약물 내용물은 제 2 약물 내용물과 상이한 제형. - 제 20 항에 있어서,
제 1 구획은 제 1 플러그에 의해 덮인 제 1 구멍을 갖고, 제 2 구획은 제 2 플러그에 의해 덮인 제 2 구멍을 갖는 제형. - 제 25 항에 있어서,
제 1 플러그는 제 2 플러그보다 긴 제형. - 제 25 항에 있어서,
제 1 플러그는 제 1 투과 속도를 갖고 제 2 플러그는 제 2 투과 속도를 갖는 제형. - 제 27 항에 있어서,
제 1 투과 속도는 제 2 투과 속도와 동일한 제형. - 제 27 항에 있어서,
제 1 투과 속도는 제 2 투과 속도보다 큰 제형. - 제 25 항에 있어서,
제 1 플러그는 제 1 침식/용해 속도를 갖고 제 2 플러그는 제 2 침식/용해 속도를 갖는 제형. - 제 30 항에 있어서,
제 1 침식/용해 속도는 제 2 침식/용해 속도와 동일한 제형. - 제 30 항에 있어서,
제 1 침식/용해 속도는 제 2 침식/용해 속도보다 큰 제형. - 제 20 항에 있어서,
제 1 구획은 제 1 벽으로 둘러싸여 있고 제 2 구획은 제 2 벽으로 둘러싸여 있는 제형. - 제 33 항에 있어서,
제 1 벽은 제 2 벽보다 두꺼운 제형. - 제 33 항에 있어서,
제 1 벽은 제 2 벽보다 침투성이 있는 제형. - 제 33 항에 있어서,
제 1 벽은 제 2 벽보다 빠르게 침식/용해되는 제형. - 함께 적층된 둘 이상의 매트릭스(matrix) 층을 포함하며, 둘 이상의 매트릭스 층의 적어도 하나는 각각 적어도 하나의 약물 내용물로 적재되는 제형.
- 제 37 항에 있어서,
둘 이상의 매트릭스 층은 서로 분리되는 제형. - 제 37 항에 있어서,
둘 이상의 매트릭스 층은 적어도 하나의 열가소성 재료로 제조되는 제형. - 제 39 항에 있어서,
적어도 하나의 열가소성 재료는 친수성 폴리머, 소수성 폴리머, 팽창성 폴리머, 비 팽창성 폴리머, 다공성 폴리머, 비 다공성 폴리머, 침식성 폴리머, 비 침식성 폴리머로 이루어진 그룹으로부터 선택되는 제형. - 제 39 항에 있어서,
적어도 하나의 열가소성 재료는 폴리바이닐 카프로락탐-폴리바이닐 아세테이트-폴리에틸렌 글리콜 그래프트 코폴리머 57/30/13, 폴리바이닐피롤리돈-코-바이닐-아세테이트 (PVP-VA), 폴리바이닐피롤리돈-폴리바이닐 아세테이트 코폴리머(PVP-VA) 60/40, 폴리바이닐피롤리돈(PVA), 폴리바이닐 아세테이트(PVAc) 및 폴리바이닐 피롤리돈(PVA) 80/20, 폴리에틸렌 글리콜-폴리바이닐 알코올 그래프트 코폴리머 25/75, 콜리코트 IR-폴리바이닐 알코올 60/40, 폴리바이닐 알코올(PVA 또는 PV-OH), 폴리(바이닐 아세테이트)(PVAc), 폴리(부틸 메타크릴레이트-코-(2-다이메틸아미노에틸)메타크릴레이트-코-메틸 메타크릴레이트) 1:2:1, 폴리(다이메틸아미노에틸메타크릴 레이트-코-메타크릴 에스터), 폴리(에틸 아크릴레이트-코-메틸 메타크릴레이트-코-트라이메틸아모니오에틸 메타크릴레이트 클로라이드), 폴리(메틸 아크릴레이트-코-메틸 메타크릴레이트-코-메타크릴산) 7:3:1, 폴리(메타크릴산-코-메틸메타크릴레이트) 1:2, 폴리(메타크릴산-코-에틸 아크릴레이트) 1:1, 폴리(메타크릴산-코-메틸 메타크릴레이트) 1:1, 폴리(에틸렌 옥사이드)(PEO), 폴리(에틸렌 글리콜)(PEG), 다분기 폴리에스터아마이드, 하이드록시프로필 메틸셀룰로오스 프탈레이트, 하이프로멜로오스 프탈레이트, 하이드록시프로필 메틸셀룰로오스 또는 하이프로멜로오스(HMPC), 하이드록시프로필 메틸셀룰로오스 아세테이트 숙시네이트 또는 하이프로멜로오스 아세테이트 숙시네이트(HPMCAS), 폴리(락티드-코-글리콜라이드)(PLGA), 카보머, 폴리(에틸렌-코-바이닐 아세테이트), 에틸렌-바이닐 아세테이트 코폴리머, 폴리에틸렌(PE) 및 폴리카프로락톤(PCL), 하이드록시 프로필 셀룰로오스(HPC), 폴리옥실 40 수소화 캐스터유, 메틸 셀룰로오스(MC), 에틸 셀룰로오스(EC), 폴록사머, 하이드록시프로필 메틸셀룰로오스 프탈레이트(HPMCP), 폴록사머, 수소화 캐스터유 및 대두유, 글리세릴 팔미토스테아레이트, 카나우바 왁스, 폴리락트산(PLA), 폴리글리콜산(PGA), 셀룰로오스 아세테이트 부티레이트(CAB), 콜로이드성 실리콘, 이산화물, 수크로오스, 글루코오스, 폴리바이닐 아세테이트 프탈레이트(PVAP) 및 이의 조합으로 이루어진 그룹으로부터 선택되는 제형. - 제 37 항에 있어서,
약물 내용물은 나노입자 형태인 제형. - 제 37 항에 있어서,
약물 내용물은 미세바늘 형태인 제형. - 제 37 항에 있어서,
약물 내용물은 네트워크 구조 또는 다공성 구조를 형성하는 제형. - 제 37 항에 있어서,
약물 내용물은 활성 약학적 성분(API)을 포함하는 제형. - 제 45 항에 있어서,
API는 국소 마취제, 통증 관리제, 수면 장애제, 항간질제 및 항경련제, 항알츠하이머제, 진통제, 항통풍제, 항고혈압제, 항부정맥제, 이뇨제, 간 질환 치료제, 췌장 질환 치료제, GI 질환 치료제, CNS 질환 치료제, 항히스타민제, 항알레르기제, 글루코코르티코이드제, 호르몬제 및 피임약, 혈당 강하제, 항골다공증제, 항생제, 설폰아마이드, 퀴놀론 및 기타 합성 항균제, 항 결핵제, 항바이러스제, 항염증제, 항종양제, 면역 조절제, 수의사 약물, 미용 활성제, 전통 중국 의약 및 전통 중국 의약의 추출물로 이루어진 그룹으로부터 선택되는 제형. - 제 37 항에 있어서,
각 매트릭스 층은 적어도 하나의 부형제를 추가로 포함하는 제형. - 제 47 항에 있어서,
부형제는 코코아 버터, 폴리에틸렌 글리콜(PEG), 수크로오스, 글루코오스, 갈락토오스, 프룩토오스, 자일로스락토오스, 말토오스, 트레할로스, 소르비톨, 만니톨, 말토덱스트린, 라피노오스, 스타키로오스, 프룩토-올리고사카라이드 및 이의 조합으로 이루어진 그룹으로부터 선택된 수용성 재료로 제조되는 제형. - 제 37 항에 있어서,
둘 이상의 매트릭스 층은 상이한 두께를 갖는 제형. - 제 37 항에 있어서,
둘 이상의 매트릭스 층은 상이한 침식/용해 속도를 갖는 제형. - 제 37 항에 있어서,
둘 이상의 매트릭스 층은 적어도 하나의 약물 내용물의 적재된 각각이 소정의 방출 프로파일에 기초하여 수용액에서 방출되도록 구성되는 제형. - 제 37 항에 있어서,
둘 이상의 매트릭스 층은 제 1 약물 내용물이 적재된 제 1 매트릭스 층 및 제 2 약물 내용물이 적재되고 제 1 매트릭스 층보다 외부에 위치된 제 2 매트릭스 층을 포함하여, 제 2 약물 내용물이 제 1 약물 내용물보다 먼저 방출되는 제형.
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