CN113939329A - 针密度不均匀的微针阵列 - Google Patents
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Classifications
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/02—General characteristics of the apparatus characterised by a particular materials
- A61M2205/0244—Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
Landscapes
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| JP2019117926 | 2019-06-25 | ||
| JP2019-117926 | 2019-06-25 | ||
| JP2019-219179 | 2019-12-03 | ||
| JP2019219179A JP7689708B2 (ja) | 2019-06-25 | 2019-12-03 | 針密度が不均一なマイクロニードルアレイ |
| PCT/JP2020/024859 WO2020262473A1 (ja) | 2019-06-25 | 2020-06-24 | 針密度が不均一なマイクロニードルアレイ |
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| CN113939329A true CN113939329A (zh) | 2022-01-14 |
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| CN202080042104.2A Pending CN113939329A (zh) | 2019-06-25 | 2020-06-24 | 针密度不均匀的微针阵列 |
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| KR (1) | KR20220024157A (https=) |
| CN (1) | CN113939329A (https=) |
| AU (1) | AU2020303770A1 (https=) |
| CA (1) | CA3143920A1 (https=) |
| WO (1) | WO2020262473A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12109032B1 (en) | 2017-03-11 | 2024-10-08 | Biolinq Incorporated | Methods for achieving an isolated electrical interface between an anterior surface of a microneedle structure and a posterior surface of a support structure |
| EP4159266A4 (en) * | 2020-05-25 | 2024-07-10 | Cosmed Pharmaceutical Co., Ltd. | HIGH-PERFORMANCE MICRO-NEEDLE ARRAY |
| CA3226577A1 (en) * | 2021-07-07 | 2023-01-12 | The Regents Of The University Of California | Wearable, non-intrusive microneedle sensor |
| WO2024108189A1 (en) * | 2022-11-17 | 2024-05-23 | Aquilx Incorporated | Wearable device with improved microneedle array |
| US12318224B2 (en) * | 2023-02-23 | 2025-06-03 | Aquilx Incorporated | Wearable biosensor device |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009240409A (ja) * | 2008-03-28 | 2009-10-22 | Toppan Printing Co Ltd | 針状体アレイおよびそのアレイ製造方法 |
| JP2010532219A (ja) * | 2007-06-29 | 2010-10-07 | カボチョン、エステティクス、インコーポレイテッド | 細胞を選択的に崩壊させるための装置および方法 |
| JP2012055343A (ja) * | 2010-09-03 | 2012-03-22 | Toray Eng Co Ltd | マイクロニードルシート及びその製造方法 |
| JP2014147837A (ja) * | 2012-06-27 | 2014-08-21 | Kosumedei Seiyaku Kk | マイクロニードルパッチの保護離型シート |
| JP2015226649A (ja) * | 2014-05-30 | 2015-12-17 | 株式会社ワークス | マイクロニードル構造体及びマイクロニードル構造体の製造方法 |
| US20160151617A1 (en) * | 2013-07-16 | 2016-06-02 | 3M Innovative Properties Company | Hollow microneedle array article |
| JP2017074196A (ja) * | 2015-10-14 | 2017-04-20 | 凸版印刷株式会社 | 針状体デバイス及びこれを備えるアプリケータ |
| CN106669025A (zh) * | 2017-01-12 | 2017-05-17 | 清华大学 | 空心金属微针阵列以及注射针头、注射器、预灌装注射器 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4090018B2 (ja) | 2002-02-18 | 2008-05-28 | Ｆｏｒ Ｈｅａｄ株式会社 | 機能性マイクロパイル及びその製造方法 |
| JP4427691B2 (ja) | 2008-04-14 | 2010-03-10 | コスメディ製薬株式会社 | マイクロニードルアレイ |
| JP4521492B2 (ja) | 2008-07-01 | 2010-08-11 | コスメディ製薬株式会社 | マイクロニードルアレイ及びその製造方法 |
| JP5903016B2 (ja) | 2012-06-27 | 2016-04-13 | コスメディ製薬株式会社 | マイクロニードルパッチの保護離型シート |
| KR102219636B1 (ko) * | 2012-12-27 | 2021-02-23 | 쓰리엠 이노베이티브 프로퍼티즈 컴파니 | 중공형 마이크로니들을 갖는 물품 및 제조 방법 |
| ES2871105T3 (es) * | 2013-07-16 | 2021-10-28 | Kindeva Drug Delivery Lp | Artículo que comprende una microaguja |
| JP2015109963A (ja) | 2013-10-30 | 2015-06-18 | 帝人株式会社 | 薬剤でコーティングされたマイクロニードルアレイの製造方法 |
| EP3067088B1 (en) * | 2013-11-05 | 2019-09-04 | Hisamitsu Pharmaceutical Co., Inc. | Applicator |
| JP6369992B2 (ja) | 2015-03-19 | 2018-08-08 | ライオン株式会社 | 溶解型マイクロニードル製剤 |
| JP6652352B2 (ja) | 2015-09-04 | 2020-02-19 | 久光製薬株式会社 | マイクロニードルデバイスの製造方法 |
| JP6726512B2 (ja) | 2016-03-31 | 2020-07-22 | コスメディ製薬株式会社 | マイクロニードルアプリケータ |
| JPWO2017213169A1 (ja) * | 2016-06-07 | 2019-03-22 | 富士フイルム株式会社 | マイクロニードルアレイ |
| US20190344062A1 (en) | 2016-12-28 | 2019-11-14 | Cosmed Pharmaceutical Co., Ltd. | Microneedle array coated with drug |
| WO2018226563A1 (en) * | 2017-06-05 | 2018-12-13 | The Board Of Trustees Of The Leland Stanford Junior University | Microneedle patches for transdermal delivery |
| CN108328567B (zh) * | 2018-01-08 | 2020-07-14 | 东南大学 | 一种获得高密度不等高晶体微针阵列的方法 |
-
2020
- 2020-06-24 WO PCT/JP2020/024859 patent/WO2020262473A1/ja not_active Ceased
- 2020-06-24 EP EP20831004.5A patent/EP3991778A4/en not_active Withdrawn
- 2020-06-24 AU AU2020303770A patent/AU2020303770A1/en not_active Abandoned
- 2020-06-24 CN CN202080042104.2A patent/CN113939329A/zh active Pending
- 2020-06-24 KR KR1020217042063A patent/KR20220024157A/ko active Pending
- 2020-06-24 CA CA3143920A patent/CA3143920A1/en active Pending
- 2020-06-24 US US17/596,403 patent/US20220241569A1/en active Pending
-
2024
- 2024-12-23 JP JP2024226324A patent/JP2025028373A/ja active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010532219A (ja) * | 2007-06-29 | 2010-10-07 | カボチョン、エステティクス、インコーポレイテッド | 細胞を選択的に崩壊させるための装置および方法 |
| JP2009240409A (ja) * | 2008-03-28 | 2009-10-22 | Toppan Printing Co Ltd | 針状体アレイおよびそのアレイ製造方法 |
| JP2012055343A (ja) * | 2010-09-03 | 2012-03-22 | Toray Eng Co Ltd | マイクロニードルシート及びその製造方法 |
| JP2014147837A (ja) * | 2012-06-27 | 2014-08-21 | Kosumedei Seiyaku Kk | マイクロニードルパッチの保護離型シート |
| US20160151617A1 (en) * | 2013-07-16 | 2016-06-02 | 3M Innovative Properties Company | Hollow microneedle array article |
| JP2015226649A (ja) * | 2014-05-30 | 2015-12-17 | 株式会社ワークス | マイクロニードル構造体及びマイクロニードル構造体の製造方法 |
| JP2017074196A (ja) * | 2015-10-14 | 2017-04-20 | 凸版印刷株式会社 | 針状体デバイス及びこれを備えるアプリケータ |
| CN106669025A (zh) * | 2017-01-12 | 2017-05-17 | 清华大学 | 空心金属微针阵列以及注射针头、注射器、预灌装注射器 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2020262473A1 (ja) | 2020-12-30 |
| KR20220024157A (ko) | 2022-03-03 |
| JP2025028373A (ja) | 2025-02-28 |
| EP3991778A1 (en) | 2022-05-04 |
| EP3991778A4 (en) | 2023-07-26 |
| AU2020303770A1 (en) | 2022-01-06 |
| US20220241569A1 (en) | 2022-08-04 |
| CA3143920A1 (en) | 2020-12-30 |
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