KR100479669B1 - Igf-1의레벨증가에유용한l-아세틸카르니틴,l-이소발레릴카르니틴,l-프로피오닐카르니틴의용도 - Google Patents
Igf-1의레벨증가에유용한l-아세틸카르니틴,l-이소발레릴카르니틴,l-프로피오닐카르니틴의용도 Download PDFInfo
- Publication number
- KR100479669B1 KR100479669B1 KR10-1998-0710960A KR19980710960A KR100479669B1 KR 100479669 B1 KR100479669 B1 KR 100479669B1 KR 19980710960 A KR19980710960 A KR 19980710960A KR 100479669 B1 KR100479669 B1 KR 100479669B1
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- KR
- South Korea
- Prior art keywords
- igf
- acetylcarnitine
- pharmaceutical composition
- isovalerylcarnitine
- propionylcarnitine
- Prior art date
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- 229960001009 acetylcarnitine Drugs 0.000 title claims abstract description 17
- UFAHZIUFPNSHSL-MRVPVSSYSA-N O-propanoyl-L-carnitine Chemical compound CCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C UFAHZIUFPNSHSL-MRVPVSSYSA-N 0.000 title claims abstract description 12
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Abstract
본 발명은 IGF-1과 관련되는 세포성 장애 또는 질병의 치료 또는 예방을 위하여 IGF-1의 레벨을 증가시키는데 이용되는 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염의 용도에 관한 것이다.
Description
본 발명은 IGF-1(insulin-like growth factor 1)과 관련된 세포성 장애 또는 질병을 치료 또는 예방하기 위하여 IGF-1의 레벨을 증가시키는데 유용한 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염의 새로운 치료학적 용도에 관한 것이다. 더욱 상세하게는 본 발명은 IGF-1에 의해 특정의 병태학적 질병이 발병했거나 또는 세포성 장애가 야기된 개체의 치료와 예방에 유용한 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염의 용도에 관한 것이다.
다른 성장 인자들과 마찬가지로 IGF-1도 세포의 성장과 분화를 촉진시킨다. 한편, 분자 생물학 방법에 따라 정제하여 단백질 형태로 얻어진 IGF-1을 체외 실험에서 동물모델과 사람에게 투여하여 세포에 미치는 효과를 관찰하였다.
본질적으로 IGF-1의 작용은 인슐린과 비슷한 바, 포도당의 이용 및 단백질 합성을 증가시키고 혈청의 지방산과 케톤을 감소시킨다. 상기의 대사 및 다른 대사에 미치는 효과와 관련하여, 여러 질병에 대한 IGF-1의 효능을 평가하기 위하여 임상 연구가 행하여졌다. IGF-1은 타입-Ⅱ의 당뇨병 환자, 악액질(cachectic) 환자, 그리고 신경계, 심근 및 신장에 허혈성의 손상이 있는 환자들의 조직의 복구 및 재생에 효과가 있다고 알려져 있다 [W.L.Lowe, Insulin-like growth factors, Scientific American Science & Medicine p.62, March 1996].
위와 같은 결과로부터 IGF-1의 투여가 다양한 병리학적인 상태에 치료학적으로 유용하다는 것이 명백하다. IGF-1의 투여로 예방, 치료 및 호전될 수 있는 질병 및 장애에 대한 예로서는 시각 신경과 후각 신경의 신경성 질환, 삼차 신경의 신경통, 벨 마비, 근위축성 측경화증과 다른 운동 근육의 신경질환, 망막의 퇴화, 골다공증, 관절병, 관절염, 목의 척추분리증과 추간판 탈출증, 키를 감소시키는 임상의 증후군, 악액질, 급성이나 만성 간장의 괴사, 터너 증후군, 사르코포니아, 성장 호르몬 무감 증후군, 당뇨병, 비만, 일반적인 무력증(특히 근무력증과 심장 무력증), 면역 결핍과 재관류 상처가 있다. 더욱이 IGF-1은 상처의 반흔화, 궤양 치유, 화상 치료, 일반적으로 조직 재생(특히 피부, 장, 간조직 재생) 그리고 상아 질 형성에도 그 유용성이 밝혀졌다.
그러나 불행하게도 사람에게 IGF-1을 투여하여 부종, 측두 하악골 관절통 및 관절통과 같은 부작용이 초래되었다. 상기의 부작용 때문에 IGF-1의 투여를 권장할 수 없을 뿐만 아니라, IGF-1 투여를 중단시킬 원인이 된다. 따라서, IGF-1의 생산을 유발할 수 있는 새로운 물질이 요구되었다.
본 발명은 외부에서 IGF-1을 투여함에 따른 부작용의 발생 문제를 해결하기 위하여 IGF-1을 투여하는 대신에 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로 피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염을 투여함으로써 IGF-1의 생산을 유도할 수 있었다.
본 발명에서의 L-아세틸카르니틴, L-이소발레릴카르니틴 또는 L-프로피오닐카르니틴의 약리학적으로 이용 가능한 염이라 함은 바람직하지 않은 독성이나 부작용을 초래하지 않는 상기 화합물과 산의 염을 의미한다. 이러한 산은 약리학자나 약제학 분야의 전문가들에게는 공지되어 있다.
이런 염의 예로는 클로라이드, 브로마이드, 아이오다이드, 아스파르테이트(바람직하기로는 하이드로겐 아스파르테이트), 시트레이트(바람직하기로는 하이드로겐 시트레이트), 타르트레이트, 포스페이트(바람직하기로는 하이드로겐 포스페이트), 푸마레이트(바람직하기로는 하이드로겐 푸마레이트), 글리세로 포스페이트, 글루코스 포스페이트, 락테이트, 말레이트(바람직하기로는 하이드로겐 말레이트), 오로테이트, 옥살레이트(바람직하기로는 하이드로겐 옥살레이트), 설페이트(바람직하기로는 하이드로겐 설페이트), 트리클로로 아세테이트, 트리플루오로 아세테이트 및 메탄술포네이트가 있으며, 본 발명은 이에 한정되지 않는다.
본 발명에서는 간결함과 설명의 편이를 위하여 L-아세틸카르니틴만을 언급하고 있으나, L-이소발레릴카르니틴, L-프로피오닐카르니틴과 이들의 약리학적으로 이용 가능한 염에도 적용된다.
심근 부정맥과 허혈성 질환, 동맥의 말초성 기능성 맥관 질환, 노인성 치매와 말초 신경계의 치료를 위한 L-아세틸카르니틴, L-이소발레릴카르니틴 및 L-프로피오닐카르니틴의 용도는 이미 알려져 있다. 그러나 이러한 치료적 용도와 본 발명의 요지와는 관련이 없다.
L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염이 사람의 생체액에서 IGF-1의 레벨을 증가시킬 수 있다는 놀라운 사실이 알려져 있다. 수많은 문헌에서 L-아세틸카르니틴의 작용기전은 대사 차원에서 미토콘드리아와 관련한 보호작용에 초점이 맞추어져 있으며, 본 발명에서는 IGF-1의 생산에 의해 중개되는 작용을 나타낸다.
본 발명의 실시예에서는 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염은 혈관 확장제, 맥관계 약제, 면역학적 약제, 내분비학적 약제, 세포증식 억제성 약제, 면역조절성 약제, 항염증성 약제 또는 코르티손 약제, IGF-1, IGF-1 결합 단백질, 성장 호르몬 그리고 표피 성장 인자 및 적아세포생성촉진제(에리스로포이에틴)와 같은 다른 세포성장인자들과 병용 투여하였다.
이와 같은 본 발명을 실시예에 의거하여 상세히 설명하면 다음과 같은 바, 본 발명의 실시예에 한정되는 것은 아니다.
실시예 1
HIV에 감염된 13명의 환자를 시험 대상으로 하였다. 8주 동안 하루에 3 g씩 L-아세틸카르니틴을 경구 투약하였고 혈액은 투약전후에 취하였다. IGF-1의 레벨은 아머샴 이탈리아 s.r.l, 밀란(Amersham Italia s.r.l., Milan)에서 제조된 키트로 측정하였고, 결과는 혈청 100 ㎕당 IGF-1의 함량을 ng 단위로 나타내었다.
상기 결과에 따르면, HIV에 감염된 환자들의 혈청내 IGF-1 레벨이 다양하다는 것을 알 수 있으며, L-아세틸카르니틴의 경구투여가 말초 혈액에서 IGF-1의 레벨을 증가시킨다는 것을 확인할 수 있었다.
실시예 2
나이가 70세 이상이며 건강한 4 명의 환자에게 L-아세틸카르니틴 2 g씩을 7일 동안 비경구 투여하였다. IGF-1을 투여하기 전과 투여한 후의 결과를 표 2에 나타내었다.
[표 2]
상술한 바와 같이 본 발명은 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 및 이들의 약리학적으로 이용 가능한 염을 사용함으로써, 외부에서 IGF-1을 투여함으로써 초래될 수 있는 바람직하지 않은 효과를 나타내지 않으면서 IGF-1의 생산을 유도할 수 있다는 것을 알 수 있었다.
Claims (4)
- 경구, 비경구, 비강, 또는 국소 투여할 수 있으며, 활성 주성분으로는 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염이 IGF-1의 레벨을 증가시키는데 효과적인 유효량이 함유되고, 그리고 약리학적으로 이용 가능한 부형제가 최소 1종 이상 포함되어 있으며,시각 신경과 후각 신경의 신경성 질환, 삼차 신경의 신경통, 벨 마비, 관절병, 관절염, 목의 척추분리증과 추간판 탈출증, 키를 감소시키는 임상의 증후군, 악액질, 급성이나 만성 간장의 괴사, 터너 증후군, 사르코포니아, 성장 호르몬 무감 증후군, 상처의 반흔화, 궤양 치유, 화상 치료, 피부, 장 및 간 조직을 포함하는 일반적인 조직 재생, 및 상아질 형성 중에서 선택된 IGF-1 관련 세포성 장애 또는 질병의 치료 또는 예방용 약제조성물.
- 제 1 항에 있어서, 상기 조성물은 활성 주성분 0.01 mg ∼ 15 g의 1일 용량을 경구, 비경구, 비강, 또는 국소 투여하는 것임을 특징으로 하는 약제학적 조성물.
- 제 1 항에 있어서, 상기 조성물은 활성 주성분 0.1 mg ∼ 10 g의 1일 용량을 경구, 비경구, 비강, 또는 국소 투여하는 것임을 특징으로 하는 약제학적 조성물.
- 제 1 항에 있어서, 상기 L-아세틸카르니틴, L-이소발레릴카르니틴, L-프로피오닐카르니틴 또는 이들의 약리학적으로 이용 가능한 염은, 혈관 확장제, 맥관계 약제, 면역학적 약제, 내분비학적 약제, 세포증식 억제성 약제, 면역조절성 약제, 항염중성 약제 또는 코르티손 약제, IGF-1, IGF-1 결합 단백질, 성장 호르몬, 또는 세포 성장 인자와 병용하여 포함된 것임을 특징으로 하는 약제학적 조성물.
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| IT96RM000479A IT1290801B1 (it) | 1996-07-05 | 1996-07-05 | Uso della acetil l-carnitina, della isovaleril l-carnitina, della propionil l-carnitina o dei loro sali farmacologicamente accettabili |
| ITRM96A000479 | 1996-07-05 | ||
| PCT/IT1997/000113 WO1998001128A1 (en) | 1996-07-05 | 1997-05-15 | Use of l-acetylcarnitine, l-isovalerylcarnitine, l-propionylcarnitine for increasing the levels of igf-1 |
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| IT1290801B1 (it) * | 1996-07-05 | 1998-12-11 | Mendes Srl | Uso della acetil l-carnitina, della isovaleril l-carnitina, della propionil l-carnitina o dei loro sali farmacologicamente accettabili |
| US6380252B1 (en) * | 1996-07-05 | 2002-04-30 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Use of L-acetylcarnitine, L-isovalerylcarnitine, L-propionylcarnitine for increasing the levels of IGF-1 |
| IT1288399B1 (it) * | 1996-12-03 | 1998-09-22 | Sigma Tau Ind Farmaceuti | Medicamento per il trattamento terapeutico della maculopatia legata all'eta', della maculopatia non legata all'eta' e per la profilassi |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0516594A1 (en) * | 1991-05-29 | 1992-12-02 | Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. | L-carnitine derivatives as therapeutical agents for treating myopathies and neuronal degeneration and for inhibiting proteolysis |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5240961A (en) * | 1992-07-02 | 1993-08-31 | Shug Austin L | Method of treating reduced insulin-like growth factor and bone loss associated with aging |
| WO1995000137A1 (de) * | 1993-06-21 | 1995-01-05 | Bernardini, Attilio | Verwendung von acylcarnitin zur behandlund von aids-krankheiten |
| IT1290801B1 (it) * | 1996-07-05 | 1998-12-11 | Mendes Srl | Uso della acetil l-carnitina, della isovaleril l-carnitina, della propionil l-carnitina o dei loro sali farmacologicamente accettabili |
-
1996
- 1996-07-05 IT IT96RM000479A patent/IT1290801B1/it active IP Right Grant
-
1997
- 1997-05-15 AT AT97922035T patent/ATE273701T1/de active
- 1997-05-15 PT PT97922035T patent/PT909171E/pt unknown
- 1997-05-15 DE DE69730330T patent/DE69730330T2/de not_active Expired - Lifetime
- 1997-05-15 JP JP10505011A patent/JP2000514437A/ja active Pending
- 1997-05-15 EP EP97922035A patent/EP0909171B1/en not_active Revoked
- 1997-05-15 US US09/147,465 patent/US6037373A/en not_active Expired - Fee Related
- 1997-05-15 KR KR10-1998-0710960A patent/KR100479669B1/ko not_active IP Right Cessation
- 1997-05-15 ES ES97922035T patent/ES2225968T3/es not_active Expired - Lifetime
- 1997-05-15 CA CA002260145A patent/CA2260145C/en not_active Expired - Fee Related
- 1997-05-15 WO PCT/IT1997/000113 patent/WO1998001128A1/en active IP Right Grant
-
2000
- 2000-02-22 US US09/510,672 patent/US6166077A/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0516594A1 (en) * | 1991-05-29 | 1992-12-02 | Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. | L-carnitine derivatives as therapeutical agents for treating myopathies and neuronal degeneration and for inhibiting proteolysis |
Also Published As
| Publication number | Publication date |
|---|---|
| US6166077A (en) | 2000-12-26 |
| DE69730330T2 (de) | 2005-02-10 |
| CA2260145A1 (en) | 1998-01-15 |
| US6037373A (en) | 2000-03-14 |
| JP2000514437A (ja) | 2000-10-31 |
| IT1290801B1 (it) | 1998-12-11 |
| CA2260145C (en) | 2007-01-09 |
| ITRM960479A0 (ko) | 1996-07-05 |
| EP0909171B1 (en) | 2004-08-18 |
| KR20000022515A (ko) | 2000-04-25 |
| PT909171E (pt) | 2004-11-30 |
| ITRM960479A1 (it) | 1998-01-05 |
| ES2225968T3 (es) | 2005-03-16 |
| WO1998001128A1 (en) | 1998-01-15 |
| EP0909171A1 (en) | 1999-04-21 |
| DE69730330D1 (de) | 2004-09-23 |
| ATE273701T1 (de) | 2004-09-15 |
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