JP6820658B2 - ジピリダモールを用いる眼疾患の治療において使用するための組成物 - Google Patents
ジピリダモールを用いる眼疾患の治療において使用するための組成物 Download PDFInfo
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- JP6820658B2 JP6820658B2 JP2015562486A JP2015562486A JP6820658B2 JP 6820658 B2 JP6820658 B2 JP 6820658B2 JP 2015562486 A JP2015562486 A JP 2015562486A JP 2015562486 A JP2015562486 A JP 2015562486A JP 6820658 B2 JP6820658 B2 JP 6820658B2
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- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 title claims description 52
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- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
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- JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
本発明は、ジピリダモールを用いる眼疾患の治療において使用するための組成物に関する。付随する説明の参照により、本発明によるこのような組成物についての態様、使用、及び利点をより理解することができる。本発明の範囲は添付の特許請求の範囲によって最も適切に定義されるものであり、当該説明は限定的な意味として解釈されるべきではなく、本発明の一般的原則を例示するのに過ぎない。以下では、本発明の例示的実施形態を以下の例示的製剤において詳細に述べる。
ジピリダモール点眼剤を以下のように調製した。100mLの生理食塩水(滅菌水中0.9%(w/v)の塩化ナトリウム)に1gのクエン酸を混合してpHを6.7とした。8.5mgのジピリダモールを秤量して滅菌のために30分間UVBを照射し、上記の100mLの生理食塩水で希釈した。その後、この溶液を、滅菌のために0.22ミクロンのフィルターでろ過し、1mL当たり85mcgのジピリダモールを含む溶液を得た。点眼器(dropper)を用いて、1滴(約0.05mLに相当)を眼に適用した。
ジピリダモール点眼剤を以下のように調製した。100mLの生理食塩水(滅菌水中0.9%(w/v)の塩化ナトリウム)に1gのクエン酸を混合してpHを6.7とした。4.25mgのジピリダモールを秤量して滅菌のために30分間UVBを照射し、上記の100mLの生理食塩水で希釈した。その後、この溶液を、滅菌のために0.22ミクロンのフィルターでろ過し、1mL当たり42.5mcgのジピリダモールを含む溶液を得た。点眼器を用いて、1滴(約0.05mLに相当)を眼に適用した。
ジピリダモール点眼剤を以下のように調製した。100mLの生理食塩水(滅菌水中0.9%(w/v)の塩化ナトリウム)に1gのクエン酸を混合してpHを6.7とした。2.125mgのジピリダモールを秤量して滅菌のために30分間UVBを照射し、上記の100mLの生理食塩水で希釈した。その後、この溶液を、滅菌のために0.22ミクロンのフィルターでろ過し、1mL当たり21.25mcgのジピリダモールを含む溶液を得た。点眼器を用いて、1滴(約0.05mLに相当)を眼に適用した。
ジピリダモール点眼剤を以下のように調製した。100mLの生理食塩水(滅菌水中0.9%(w/v)の塩化ナトリウム)に1gのクエン酸を混合してpHを6.7とした。1.0625mgのジピリダモールを秤量して滅菌のために30分間UVBを照射し、上記の100mLの生理食塩水で希釈した。その後、この溶液を、滅菌のために0.22ミクロンのフィルターでろ過し、1mL当たり10.625mcgのジピリダモールを含む溶液を得た。点眼器を用いて、1滴(約0.05mLに相当)を眼に適用した。
GvHDに関連するドライアイに罹患した5人の男性を、毎日2回、左右両方に対して1滴ずつの製剤Aで処置した。ドライアイ症状の主観的な緩和が半時間以内に達成された。患者はその後、毎日2回の適用を必要とした。3日間の使用の後、眼の充血(またはピンクアイ(pink eye))は消失した。
ジピリダモールを滅菌水に溶解することにより、ジピリダモール点眼剤を調製した。必要に応じてpHを調整し、溶解を達成した。5mcg/ml〜200mcg/mlの範囲の複数の濃度で調製した。その後、滅菌処置をおこなった。
シェーグレンに関連するドライアイ:滴剤/軟膏を適用すると、一過性の刺すような感覚が僅かに得られた。ドライアイ症状の部分的な緩和が、適用して1時間以内に起こった。緩和は、約7日間の継続使用の後に完全なものとなり、一部の患者において毎日投与することで、ならびに、他の患者において周期的(3〜4日毎)に投与することで継続した。
ジピリダモールを用いた組成物は眼疾患の治療において利用され、このような疾患に関連する問題を克服する技術革新である。
Claims (9)
- 涙器系又は前眼部の眼疾患の治療において使用するための医薬組成物であって、5mcg/ml〜200mcg/mlの濃度での有効な量の局所的に投与されるジピリダモールまたはその薬学的に許容可能な塩を含み、前記涙器系又は前眼部の眼疾患が、角膜炎、角膜潰瘍、角膜血管新生、乾性角結膜炎、ドライアイ、角膜知覚消失、流行性結膜炎(pink eye)、眼球乾燥症、ブドウ膜炎、翼状片、角膜症、又は瞼裂斑である、医薬組成物。
- 前記医薬組成物は、溶液である、請求項1に記載の医薬組成物。
- 前記医薬組成物は、水溶液である、請求項2に記載の医薬組成物。
- 前記溶液のpHは、6.7以下に調整される、請求項3に記載の医薬組成物。
- 前記溶液のpHは、6.5〜6.7に調整される、請求項4に記載の医薬組成物。
- 前記組成物は、少なくとも10−5のモル濃度のジピリダモールを含む、請求項1〜5のいずれか1項に記載の医薬組成物。
- 前記組成物は、1日おきに少なくとも1回局所的に投与される、請求項1〜6のいずれか1項に記載の医薬組成物。
- 前記組成物は、対象に1日あたり240μgまでのジピリダモールを局所的に投与するために使用される、請求項1〜7のいずれか1項に記載の医薬組成物。
- 涙器系又は前眼部の眼疾患の治療において使用するための医薬組成物であって、有効な量の局所的に投与されるジピリダモールまたはその薬学的に許容可能な塩を含み、前記涙器系又は前眼部の眼疾患が、角膜炎、角膜潰瘍、角膜血管新生、乾性角結膜炎、ドライアイ、角膜知覚消失、流行性結膜炎(pink eye)、眼球乾燥症、ブドウ膜炎、翼状片、角膜症、又は瞼裂斑である、医薬組成物。
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IL225179A IL225179A (en) | 2013-03-12 | 2013-03-12 | Compounds for use in ocular disorders using dipyridamole |
IL225179 | 2013-03-12 | ||
PCT/IB2014/059645 WO2014141079A1 (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
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US20180092776A1 (en) | 2016-09-30 | 2018-04-05 | Sara Heikali | Method and device for treating and managing diseased ocular tissue |
WO2021001806A1 (en) | 2019-07-04 | 2021-01-07 | Ocular Discovery Ltd. | Stable dipyridamole formulations with reduced impurities |
WO2021001805A1 (en) | 2019-07-04 | 2021-01-07 | Ocular Discovery Ltd. | Stable dipyridamole formulations and their methods of preparation |
WO2024125322A1 (zh) * | 2022-12-16 | 2024-06-20 | 智泽童康(广州)生物科技有限公司 | 防治过敏性和/或炎症性疾病的双嘧达莫及其制剂 |
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JPH07258084A (ja) * | 1994-03-17 | 1995-10-09 | Rohto Pharmaceut Co Ltd | ジピリダモールを必須成分とする眼圧降下剤 |
US5780450A (en) * | 1995-11-21 | 1998-07-14 | Alcon Laboratories, Inc. | Use of adenosine uptake inhibitors for treating retinal or optic nerve head damage |
US20060104968A1 (en) * | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
ZA200804550B (en) * | 2005-11-09 | 2009-08-26 | Combinatorx Inc | Methods, compositions, and kits for the treatment of medical conditions |
WO2010056710A1 (en) * | 2008-11-11 | 2010-05-20 | Biovista, Inc. | Compositions and methods for treating eye diseases |
EP2363126A1 (en) * | 2010-03-04 | 2011-09-07 | SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. | Composition comprising as active ingredient L-carnitine in combination with hydroxykynurenine-O-beta-DL-glucoside, for the prevention and/or treatment of pathologies of the eye due to ultraviolet radiation |
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CL2015002627A1 (es) | 2016-03-11 |
MX2015012716A (es) | 2016-07-06 |
CN105188702B (zh) | 2019-03-26 |
IL225179A (en) | 2017-01-31 |
SG11201507092QA (en) | 2015-10-29 |
BR112015022084A2 (pt) | 2017-07-18 |
EP2968328A4 (en) | 2016-11-23 |
MY182591A (en) | 2021-01-26 |
SG10201706937UA (en) | 2017-09-28 |
EP2968328A1 (en) | 2016-01-20 |
EA035966B1 (ru) | 2020-09-07 |
AU2014229371B2 (en) | 2018-05-10 |
KR20150126021A (ko) | 2015-11-10 |
CA2905594A1 (en) | 2014-09-18 |
CN105188702A (zh) | 2015-12-23 |
AU2014229371A1 (en) | 2015-10-29 |
WO2014141079A1 (en) | 2014-09-18 |
KR20210010638A (ko) | 2021-01-27 |
IL225179A0 (en) | 2013-06-27 |
JP2016514123A (ja) | 2016-05-19 |
EA201591653A1 (ru) | 2017-05-31 |
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