KR100694907B1 - 아테롬성동맥경화 치료제로서의 프로안토시아니딘 ａ2의인지질 착체 - Google Patents
아테롬성동맥경화 치료제로서의 프로안토시아니딘 ａ2의인지질 착체 Download PDFInfo
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- proanthocyanidin
- phospholipid
- complex
- atherosclerosis
- complexes
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- NSEWTSAADLNHNH-TXZJYACMSA-N Proanthocyanidin A-2 Natural products C1([C@H]2OC3=C4[C@H]5C6=C(O)C=C(O)C=C6O[C@]([C@@H]5O)(OC4=CC(O)=C3C[C@@H]2O)C=2C=C(O)C(O)=CC=2)=CC=C(O)C(O)=C1 NSEWTSAADLNHNH-TXZJYACMSA-N 0.000 title claims abstract description 23
- 229920002982 Procyanidin A2 Polymers 0.000 title claims abstract description 23
- NSEWTSAADLNHNH-UHFFFAOYSA-N pavetannin A-2 Natural products OC1CC2=C(O)C=C3OC(C4O)(C=5C=C(O)C(O)=CC=5)OC5=CC(O)=CC(O)=C5C4C3=C2OC1C1=CC=C(O)C(O)=C1 NSEWTSAADLNHNH-UHFFFAOYSA-N 0.000 title claims abstract description 23
- NSEWTSAADLNHNH-LSBOWGMISA-N proanthocyanidin A2 Chemical compound C1([C@H]2OC3=C4[C@H]5C6=C(O)C=C(O)C=C6O[C@]([C@@H]5O)(OC4=CC(O)=C3C[C@H]2O)C=2C=C(O)C(O)=CC=2)=CC=C(O)C(O)=C1 NSEWTSAADLNHNH-LSBOWGMISA-N 0.000 title claims abstract description 23
- 150000003904 phospholipids Chemical class 0.000 title claims abstract description 19
- 230000000879 anti-atherosclerotic effect Effects 0.000 title abstract 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 8
- 206010008118 cerebral infarction Diseases 0.000 claims description 7
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 6
- 239000007903 gelatin capsule Substances 0.000 claims description 3
- 235000010445 lecithin Nutrition 0.000 claims description 3
- 239000000787 lecithin Substances 0.000 claims description 3
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
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- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims 5
- 239000004480 active ingredient Substances 0.000 claims 3
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- 230000003143 atherosclerotic effect Effects 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 2
- 230000007170 pathology Effects 0.000 abstract 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 16
- 235000012000 cholesterol Nutrition 0.000 description 8
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000003902 lesion Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- JLPULHDHAOZNQI-JLOPVYAASA-N [(2r)-3-hexadecanoyloxy-2-[(9e,12e)-octadeca-9,12-dienoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC JLPULHDHAOZNQI-JLOPVYAASA-N 0.000 description 3
- 229920002770 condensed tannin Polymers 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
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- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- -1 3,4-dihydroxyphenyl Chemical group 0.000 description 1
- 241000157280 Aesculus hippocastanum Species 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010048964 Carotid artery occlusion Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
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- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108010069201 VLDL Cholesterol Proteins 0.000 description 1
- 230000003035 anti-peroxidant effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 210000004004 carotid artery internal Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
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- 230000001120 cytoprotective effect Effects 0.000 description 1
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- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
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- 235000010181 horse chestnut Nutrition 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
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- 235000021003 saturated fats Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
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- 230000001643 venotonic effect Effects 0.000 description 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
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Abstract
프로안토시아니딘 A2(proanthocyanidin A2)의 인지질 착체(phospholipid complexes)는 아테롬성 동맥경화 병리현상의 예방 및 치료에 유용하다.
프로안토시아니딘 A2(proanthocyanidin A2), 인지질 착체(phospholipid complexes), 아테롬성 동맥경화치료제(Anti atherosclerotic agents).
Description
본 발명은 프로안토시아니딘 A2(proanthocyanidin A2) 또는 프로안토시아니딘 A2가 강화된 추출물의 인지질 착체(phospholipid complexes)및 이들을 함유한 아테롬성동맥경화(atherosclerosis), 심근경색(myocardial infaction) 및 뇌경색 (cerebral infarction)의 예방 및 치료를 위한 의약품의 제조를 위한 용도에 관한 것이다.
프로안토시아니딘 A2는 하기 구조식(Ⅰ)의 8,14-메타노-2H,14H-1-벤조피라노 [7,8-d] [1,3]벤조디옥소신-3,5,11,13,15-펜톨-2,8-비스-(3,4-디히드록시페닐)3,4 -디히드로[2R-2α,3α,8β,14β,15R]로서, 아에스쿨러스 히포카스타눔(Aesculus hippocastanum)의 씨로부터 분리되었다(Tetrahedorn Lett.,429,1966참조).
프로안토시아니딘 A2의 상처치료(cicatrising), 세포보호(cytoprotective), 항궤양(antiulcer), 정맥강화(venotonic), 혈관보호(vasoprotective)및 항과산화제 (antiperoxidative agent)로서의 용도는 EP-A-210780호(1987. 2.4.공개)에 개시되어 있다.
우리는 프로안토시아니딘 A2의 인지질 착체가 동물이나 인체에 전신 투여시, 바람직하게는 경구경로를 통한 투여시 아테롬성동맥경화 치료작용을 갖는다는 놀라운 사실을 발견하고 본 발명을 완성하기에 이른 것이다.
본 발명의 착체(complexes)는, 프로안토시아니딘 A2(proanthocyanidin A2)와 레시틴(lecithins), 포스파티딜콜린(phosphatidylcholine), 포스파티딜세린 (phosphatidylserine), 또는 포스파티딜에탄올아민(phosphatidylethanolamine)과 같은 천연 또는 합성 인지질로 구성 될 수 있다. 프로안토시아니딘 A2와 인지질의 비율은 2:1 내지 1:2의 범위이고, 바람직한 것은 약 1:1.5 w/w이다. 특히 바람직한 착체는 콩 포스파티딜콜린(soy phosphatidylcholine)과의 착체이다.
본 발명의 착체(complexes)는, 인지질 용액과 프로안토시아니딘 A2용액을 적당한 용매, 즉 아세톤, 에틸아세테이트, 에탄올과 같은 용매 중에서 반응시킨 후, 반응혼합물을 감압하 농축시켜 두꺼운 잔사를 만들고 이것을 분쇄하여 제조한다. 본 발명의 착체(complexes)는 용량의존적으로 아테롬성동맥경화성 혈소판 (atherosclerotic plaques)의 형성을 예방 또는 감소시킨다. 그 효과는 토끼에 콜레스테롤 강화식품(hypercholesterolemic diet)을 먹여서 혈관 수준, 특히 대동맥 궁(aortal arch), 복면대동맥(ventral aorta), 경동맥(carotids), 뇌혈관(cerebral vessels)에서 인체와 유사한 아테롬성동맥경화 병변을 유발시킨 토끼에서 입증되었다. 이 모델에서 상기 언급한 인지질 착체는 비투여 동물군과 비교하였을 때 거시적, 미시적인 혈관 조건을 변화시켰는데, 놀랄만한 혈관-조직상의 개선 이점을 가지고, 죽종 혈소판(athoeromatous plaques)의 수와 강도를 모두 감소시켰다. 뇌보호를 목적으로 한 또다른 아테롬성동맥경화 모델은 토끼에게 포화 지방이 많이 들어있는 콜레스테롤 강화식품(hypercholesterolemic diet)을 먹이면서 토끼의 내부 경동맥 혈관내경을 수술로 작게 한 것이었는데 이 모델에서는 경동맥 폐쇄가 감소하였고, 혈관벽 두께가 줄어들었으며, 동물들의 생존율 연장이 관찰되었다. 나아가, 아테롬성동맥경화 환자에게 6 개월 투여후 도플러 초음파 검사(Doppler ultrasongraphy)를 수행한 결과, 죽종 혈소판(athoeromatous plaques)으로 인한 경동맥 폐쇄가 감소하였고, 경동맥 혈류가 개선되었음을 보여주었다.
프로안토시아니딘 A2의 인지질 착체는 경구경로를 위한 적절한 투여 형태로 사용될 수가 있는데, 예를 들어 정제나 연질 또는 경질 젤라틴 캅셀 등이고, 질병의 중증도에 따라 50 내지 500 mg 범위의 투여량이 1 일 2-3 회 투여되었다. 의약적 조성물은 종래의 기술과 부형제를 사용하여 제조될 수 있다.
하기 실시예들이 본 발명을 더 자세하게 설명하고 있다.
실시예 1
프로안토시아니딘 A2의 포스파티딜콜린과의 착체 제조
포스파티딜콜린 1,577 g을 에틸 아세테이트 5 리터에 녹인 용액을 70℃로 유 지하고, 프로안토시아니딘 A2 1 kg을 아세톤 5 리터에 녹인 용액을 가하였다.
혼합액을 환류 교반한 다음, 감압 증류하여 건조하였다. 잔사를 50℃에서 24 시간 감압 건조한 후 원하는 입자 크기로 분쇄하였다.
실시예 2
뉴질랜드 토끼 32 마리를 8 마리씩 네군으로 나누고 하기와 같이 처치하였다.
1군 : 대조군, 정상 식이
2군 : 콜레스테롤 강화식이(0.2 % w/w 콜레스테롤)
3군 : 콜레스테롤 강화식이 + 프로안토시아니딘 A2 추출물의 인지질 착체( 0.2 % 콜레스테롤 + 2 % w/w 실시예 1 착체)
4군 : 콜레스테롤 강화식이 + 프로안토시아니딘 A2 추출물(0.2% 콜레스테롤 + 2 % w/w 실시예 1 착체에 존재하는 양에 해당하는 프로안토시아니딘 A2의 양) 콜레스테롤, LDL/VLDL, HDL 및 지방(triglcerides)의 양을 측정하면서 8 주간 투여후, 동물들을 치사시켰다.
흉부(thoracic)및 복부 대동맥(abdominal aorta)의 아테롬성동맥경화 병변의수, 크기 및 분포가 측정되었다.
대동맥 대(aorta strips)를 고정시키고, 수단 Ⅳ(Sudan Ⅳ)로 염색하여 병변을 관찰할 수 있도록 한 다음, 혈관 콜레스테롤과 산화 콜레스테롤의 양을 가스크로마토그래피로 측정하였다.
하기 표에 기재된 결과들은, 프로안토시아니딘 A2의 인지질 착체를 투여한 결과 콜레스테롤 강화식이에 의해 유발된 아테롬성동맥경화 병변이 통계적으로 유의성있게 감소하였음을 입증하고 있다.
(표)
| 처 치 | 병변의 면적퍼센트 |
| 1군 | 0.5 % |
| 2군 | 34 % |
| 3군 | 7.5 %* |
| 4군 | 30 % |
*2군과 비교시 p<0.01.
실시예 3
프로안토시아니딘 A2의 인지질 착체 500 mg을 함유한 캅셀
조성:
프로안토시아니딘 A2의
콩 포스파티딜콜린과의 착체 150 mg
유당 57 mg
변형 전분 40 mg
스테아린산 마그네슘 3.0 mg
실시예 4
위-저항성 정제(Gastro-resistant tablets)
프로안토시아니딘 A2의
콩 포스파티딜콜린과의 착체 200 mg
미세결정형 셀룰로오스 118 mg
침강 실리카 3 mg
스테아린산 마그네슘 4 mg
메타크릴산(methacrylic acid)음이온
폴리머와 그 에스테르 12 mg
활석 8 mg
탄산 마그네슘 8 mg
옥수수 전분 5 mg
아라비아 검 159 mg
실시예 5
연질-젤라틴 캅셀
프로안토시아니딘 A2의
콩 포스파티딜콜린과의 착체 216 mg
땅콩 오일 209 mg
부분 수소화된 식물성 기름 100 mg
콩 레시틴(soy lecithin) 5 mg
Claims (9)
- 프로안토시아니딘 A2의 인지질 착체(phospholipid complexes).
- 제 1항에 있어서, 인지질이 레시틴(lecithins), 포스파티딜콜린 (phosphatidylcholine), 포스파티딜에탄올아민(phosphatidylethanolamine) 또는 포스파티딜세린(phosphatidyleserine)중에서 선택된 착체.
- 제 2항에 있어서, 인지질이 포스파티딜콜린(phosphatidylcholine)인 착체.
- 제 1항 내지 제3항 중 어느한 항에 있어서, 프로안토시아니딘 A2와 인지질의 중량비가 (weight ratio)가 2:1 내지 1:2의 범위 내에 있는 착체.
- 청구항 1항의 프로안토시아니딘 A2의 인지질 착체를 유효성분으로 하는 아테롬성동맥경화, 심근경색 및 뇌경색의 예방 또는 치료제.
- 제 5항에 있어서, 의약품의 단일 용량이 활성 성분을 50 내지 500 mg의 범위 내에 있는 아테롬성동맥경화, 심근경색 및 뇌경색의 예방 또는 치료제.
- 제 5항 또는 제6항 중 어느 한 항에 있어서, 의약품이 경구경로를 통하여 투여가능한 아테롬성동맥경화, 심근경색 및 뇌경색의 예방 또는 치료제.
- 제 7항에 있어서, 의약품이 연질 또는 경질 젤라틴 캅셀 또는 정제의 형태인 아테롬성동맥경화, 심근경색 및 뇌경색의 예방 또는 치료제.
- 활성성분으로서 청구항 1항의 프로안토시아니딘 A2의 인지질 착체와 담체로 구성된 아테롬성동맥경화, 심근경색 및 뇌경색의 예방 또는 치료용 약제학적 조성물.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI98A002732 | 1998-12-18 | ||
| IT1998MI002732A IT1304183B1 (it) | 1998-12-18 | 1998-12-18 | Complessi di proantocianidina a2 con fosfolipidi come agentiantiaterosclerotici. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20010093826A KR20010093826A (ko) | 2001-10-29 |
| KR100694907B1 true KR100694907B1 (ko) | 2007-03-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020017007374A KR100694907B1 (ko) | 1998-12-18 | 1999-12-13 | 아테롬성동맥경화 치료제로서의 프로안토시아니딘 ａ2의인지질 착체 |
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| Country | Link |
|---|---|
| US (1) | US6429202B1 (ko) |
| EP (1) | EP1140115B1 (ko) |
| JP (1) | JP4842436B2 (ko) |
| KR (1) | KR100694907B1 (ko) |
| CN (1) | CN1146429C (ko) |
| AT (1) | ATE238803T1 (ko) |
| AU (1) | AU763907B2 (ko) |
| CA (1) | CA2355776C (ko) |
| CZ (1) | CZ301495B6 (ko) |
| DE (1) | DE69907509T2 (ko) |
| DK (1) | DK1140115T3 (ko) |
| ES (1) | ES2197708T3 (ko) |
| HK (1) | HK1042430B (ko) |
| HU (1) | HU228928B1 (ko) |
| IL (2) | IL143751A0 (ko) |
| IT (1) | IT1304183B1 (ko) |
| NO (1) | NO328733B1 (ko) |
| PL (1) | PL197153B1 (ko) |
| PT (1) | PT1140115E (ko) |
| RU (1) | RU2248798C2 (ko) |
| SK (1) | SK284884B6 (ko) |
| WO (1) | WO2000037062A2 (ko) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8507018B2 (en) * | 1998-03-12 | 2013-08-13 | Mars, Incorporated | Products containing polyphenol(s) and L-arginine and methods of use thereof |
| AU2003226974A1 (en) * | 2002-02-12 | 2003-09-04 | Hunza Di Pistolesi Elvira And C. S.A.S. | N-acyl-phosphatidyl-ethanolamines and/or mixtures of n-acyl-ethanolamines with phosphatidic acids or lysophosphatidic acids |
| ITMI20020756A1 (it) * | 2002-04-09 | 2003-10-09 | Sinclair Pharma S R L | Composizioni farmaceutiche topiche per il trattamento delle dermatiti |
| GB0321996D0 (en) * | 2003-09-19 | 2003-10-22 | Novartis Nutrition Ag | Organic compounds |
| AU2005209317B2 (en) * | 2004-01-28 | 2011-07-07 | Mars, Incorporated | Compositions and methods of use of A-type procyanidins |
| EP1837030A1 (en) | 2006-03-09 | 2007-09-26 | INDENA S.p.A. | Phospholipid complexes of curcumin having improved bioavailability |
| JP5443015B2 (ja) * | 2008-02-19 | 2014-03-19 | 株式会社岐阜セラツク製造所 | 医薬組成物 |
| IT1398624B1 (it) * | 2009-02-02 | 2013-03-08 | Dermogyn S R L | Uso cosmetico della proantocianidina a2 |
| RU2456674C1 (ru) * | 2011-05-31 | 2012-07-20 | Тагир Уралович Гафаров | Способ моделирования атрофического рубца кожи |
| CN102688501A (zh) * | 2012-06-20 | 2012-09-26 | 浙江萧山医院 | 原花青素b2磷脂复合物及其制备方法和用途 |
| CN103120798A (zh) * | 2013-01-10 | 2013-05-29 | 施冬云 | 一种具有抗氧化应激作用的磷脂复合物制备方法及其应用 |
| CN103467778B (zh) * | 2013-09-06 | 2015-09-30 | 天津大学 | 细菌纤维素/卵磷脂复合材料及制备和应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648377A (en) * | 1993-12-21 | 1997-07-15 | Indena S.P.A. | Formulations containing carotenoids an procarotenoids combined with polyphenols in the prevention of the damages due to an abnormal production of free radicals |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4698360B1 (en) * | 1985-04-09 | 1997-11-04 | D Investigations Pharmacologiq | Plant extract with a proanthocyanidins content as therapeutic agent having radical scavenger effect and use thereof |
| GB8518289D0 (en) * | 1985-07-19 | 1985-08-29 | Inverni Della Beffa Spa | Obtaining proanthocyanidine a2 |
| IT1201151B (it) * | 1987-01-14 | 1989-01-27 | Indena Spa | Complessi fosfolipidici con estratti da vitis vinifera,procedimento per la loro preparazione e composizioni che li cntengono |
| IT1201149B (it) * | 1987-01-14 | 1989-01-27 | Indena Spa | Complessi di bioflavonoidi con fosfolipidi,loro preparazione,uso e composizioni farmaceutici e cosmetiche |
| IT1265312B1 (it) * | 1993-12-21 | 1996-10-31 | Indena Spa | Formulazioni contenenti carotenoidi e procarotenoidi associati a polifenoli nella prevenzione dei danni da abnorme produzione di |
| IT1270999B (it) * | 1994-07-26 | 1997-05-26 | Indena Spa | Formulazioni a base di cumarine e loro uso in campo farmaceutico e cosmetico |
| FI955691A (fi) * | 1994-11-28 | 1996-05-29 | Suntory Ltd | Lipoproteiini(a):ta alentava aine, kolesterolia alentava aine ja näitä aineita sisältävät lääkkeet |
| IT1296920B1 (it) * | 1997-12-04 | 1999-08-03 | Indena Spa | Uso di complessi di estratti vitis vinifera con fosfolipidi come agenti anti-aterosclerotici |
| EP1210785B1 (de) | 1999-09-08 | 2005-11-23 | Siemens Aktiengesellschaft | Anordnung und verfahren für eine optische informationsübertragung |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648377A (en) * | 1993-12-21 | 1997-07-15 | Indena S.P.A. | Formulations containing carotenoids an procarotenoids combined with polyphenols in the prevention of the damages due to an abnormal production of free radicals |
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