珪藻土（diatomaceous earth）を有効成分とする止血剤と、メッシュレセプタクルやスポンジ基材への担持・放出制御を含むデバイス設計が出願されています（Z‑Medica/Teleflexファミリー）。Hemostatic agents and devices for the delivery thereof
タンパク質搭載パッド
乾燥（凍結乾燥）フィブリノゲンやトロンビンを生体吸収性スキャフォールドに搭載する止血パッド/キットが提案されています（Ethicon）。Hemostatic Pad Assembly Kit and Method
骨表面の滲出性出血に対し、骨蝋を吸収材に一体化し安全に押し込むアプリケータとトレイ保持モジュールの提案があります（TRW系）。Method of making and using a hemostatic agent applicator+1
穿刺創・生検トラクト対応
カートリッジ・シース・ピストン構成で止血材を穿刺孔へ確実送達するデバイスや、プラジェット＋止血剤＋粒子の懸濁液でトラクトをパッキングする方法が開示されています。HEMOSTATIC MATERIAL AND DEVICE FOR ACHIEVING DURABLE HEMOSTASIS OF A BLEEDING BIOPSY TRACT+1
圧迫バンドのスマート化
橈骨動脈などの止血バンドに圧力センサと最適圧制御・フィードバックを備えた監視システムが近年の特許で示されています（Terumo）。Monitoring system for a hemostasis band
ユーザー支援ウェアラブル
吸収布層に止血剤を担持した手袋で手技と圧迫を一体化する救急・外傷向け提案があります（Innovative Trauma Care）。Hemostatic glove device and method for use of same+1
代表的な公報例
US20070276308A1（Z‑Medica/Teleflex）：珪藻土粉体を用いた止血剤、メッシュレセプタクル、止血スポンジなどのバリエーションをクレーム。Hemostatic agents and devices for the delivery thereof
US20150017225A1／US10765774B2等（Ethicon）：生体吸収性スキャフォールドに凍結乾燥フィブリノゲン/トロンビンを搭載するパッドとその使用法。Hemostatic Pad Assembly Kit and Method
US20220008258A1：生検トラクトをプラジェット＋止血剤＋微粒子でパッキングする懸濁液送達法。HEMOSTATIC MATERIAL AND DEVICE FOR ACHIEVING DURABLE HEMOSTASIS OF A BLEEDING BIOPSY TRACT
US12193681B2（Terumo）：止血バンドの圧力センサ計測と最適圧比較・フィードバックを行う監視システム。Monitoring system for a hemostasis band
US9839561B2／US20140163484A1：止血剤担持の手袋デバイスと使用法。HEMOSTATIC GLOVE DEVICE AND METHOD FOR USE OF SAME+1
素材・設計トレンド
無機吸着材（ゼオライト/珪藻土等）から、タンパク質系（フィブリノゲン/トロンビン）、ECM由来マトリクス、骨蝋など幅広い材料が採用され、担持形態や放出制御で差別化が進んでいます。Method of making and using a hemostatic agent applicator+3
送達・適用性の工夫（カートリッジ送達、プラジェット懸濁、手袋一体化、センサ付きバンド）により、部位特異的・手技効率・安全性を高める方向が見られます。Hemostatic glove device and method for use of same+3
クレームは粒径範囲、含有量、スキャフォールド構造、乾燥形態、吸収性、センサ閾値や最適圧アルゴリズムなど、定量パラメータでの限定が多い傾向です。Hemostatic Pad Assembly Kit and Method+2
主な出願人の傾向
Z‑Medica／Teleflex：無機粉体系止血剤とその送達デバイス群。Hemostatic agents and devices for the delivery thereof
Ethicon（Johnson & Johnson）：タンパク質搭載止血パッドとキットの改良継続。Hemostatic Pad Assembly Kit and Method
ACell：ECM由来の生体吸収性止血材の応用拡張。HEMOSTATIC DEVICE
Terumo：止血バンドの圧力監視・最適圧制御のスマート化。Monitoring system for a hemostasis band
TRW：骨蝋アプリケータの古典的改良群。Method and device for delivering a hemostatic agent to an operating status+1
Innovative Trauma Care：救急用途の止血手袋デバイス。HEMOSTATIC GLOVE DEVICE AND METHOD FOR USE OF SAME+1
実務上の示唆
競合回避には、材料×形態（粉体／繊維化／多孔質）に加え、送達・保持メカニズム（メッシュレセプタクル、粘着性調整、プラジェット混合）やユーザー操作性（手袋、カテ先端、バンドセンサ）での新規構成が有効です。HEMOSTATIC MATERIAL AND DEVICE FOR ACHIEVING DURABLE HEMOSTASIS OF A BLEEDING BIOPSY TRACT+3
臨床適応別（骨、肝脾、穿刺孔、橈骨動脈、外傷）に合わせた粒径、粘度、乾燥形態、圧設定、センサしきい値などの定量条件を発明の核に据えるとクレームの実効性が高まります。Monitoring system for a hemostasis band+2
結論：穿刺閉鎖（血管アクセスや生検トラクトの止血・封止）では、直近5年にTerumo、Abbott、Cardiva、個人発明（バルーン閉鎖）などから、シース内ノズルによる凝固促進材注入、アンカー＋エクストラバスキュラーキャップ＋シーラント（PEG等）、バルーンでの内腔圧迫、懸濁液（プラジェット＋止血剤＋粒子）でのトラクトパッキング、圧迫バンドの最適圧モニタリングといった多様なアプローチで出願・権利化が進んでいます。VASCULAR CLOSURE DEVICE AND RELATED METHODS+7
抽出条件
用途：穿刺閉鎖（血管アクセス部／生検トラクトの止血・封止）を対象。VASCULAR CLOSURE DEVICE AND RELATED METHODS
期間：直近5年（2020-11-14〜2025-11-14）に公開・登録の米国特許文献を抽出。Vascular closure device and related methods
主分類候補：A61B17/00系（血管閉鎖デバイス）、A61B10/00系（生検関連）、A61L24/00・A61L31/00（医用封止材）などを含む公報を採用。VESSEL CLOSURE DEVICE WITH IMPROVED SAFETY AND TRACT HEMOSTASIS+1
出願一覧（直近5年、穿刺閉鎖）
出願/特許
出願人
主分類
公開/登録年
技術要点
US20210338217A1 → US11690607B2
Terumo Medical
A61B17/3423 等
2021公開/2023登録
シース内ノズルからトラクトにプロコアグラントを注入し、血管壁近傍で止血・閉鎖する方法/装置VASCULAR CLOSURE DEVICE AND RELATED METHODS+1。
US20220110617A1 → 継続出願あり
Abbott Cardiovascular
A61B17/0057, A61L24/06 等
2022公開
アンカー＋エクストラバスキュラーキャップ＋シーラント（PEG等）＋縫合糸の生体適合素材一体系で即時止血とトラクト止血性を両立VESSEL CLOSURE DEVICE WITH IMPROVED SAFETY AND TRACT HEMOSTASIS。
US20240350136A1（継続）
Abbott Cardiovascular
A61L24/06, A61B17/0057 等
2024公開
上記構成の安全性・トラクト止血性を改良した後続出願（素材・手順最適化）VESSEL CLOSURE DEVICE WITH IMPROVED SAFETY AND TRACT HEMOSTASIS。
素材ではPEG系シーラントや止血剤の薬剤溶出/担持が再活発で、完全バイオ材料構成の一体化デバイスが志向されています。VESSEL CLOSURE DEVICE WITH IMPROVED SAFETY AND TRACT HEMOSTASIS+1
追加対応の提案
JP同族の有無と具体的IPC小分類（例：A61B17/0057, A61B17/3423, A61B10/0041, A61L24/06）での件数推移グラフ、主要クレームの数値比較（粒径、注入量、圧設定）を拡張可能です。HEMOSTATIC MATERIAL AND DEVICE FOR ACHIEVING DURABLE HEMOSTASIS OF A BLEEDING BIOPSY TRACT+3
特定競合（Abbott/Terumo/Cardiva）に絞った請求項の独立請求項マッピングと回避設計案も提示できます。VESSEL CLOSURE DEVICE WITH IMPROVED SAFETY AND TRACT HEMOSTASIS+2
Patents are the artifacts of an age-old process: humans turning curiosity and ingenuity into practical innovation to benefit their fellow citizens. （Introducing Perplexity Patents）
大学の事務屋さん（学内文書・Excel/SharePoint、ワークフロー自動化、承認系）
→ Microsoft Copilot Studio エージェント：M365/Teams/SharePoint/Power Automate 連携、マルチエージェント編成、管理者ガバナンスが充実。(Microsoft)
「予約・資料収集・比較表・プレゼンまで一気通貫」の自律実行体験
→ Manus／GenSpark Super Agent：Webブラウズしながら段取り→実行。GAIA系ベンチでの自己申告も含め話題。(Manus AI)
Case Report of Very-Low-Dose Fentanyl Causing Fentanyl-Induced Chest Wall Rigidity Ronza Zoorob, Logan Uptegrove, Benjamin L Park Cureus. 2023 Aug 20;15(8):e43788. doi: 10.7759/cureus.43788 https://pmc.ncbi.nlm.nih.gov/articles/PMC10508708/
Opioid-induced rigidity after intravenous fentanyl C M Viscomi 1, P L Bailey Affiliations Expand PMID: 9166335 DOI: 10.1016/s0029-7844(97)81423-8 Obstet Gynecol . 1997 May;89(5 Pt 2):822-4. doi: 10.1016/s0029-7844(97)81423-8. 本文有料
Welcome back to the Deep Dive. Today we’re taking you inside one of the most legendary research labs of the 20th century.
That’s right. We’re talking about the Numakin, Dr. Shosaku Numa’s lab at Kyoto University back in Japan’s Showa era.
Numa was a giant in molecular neurobiology, active really up until his passing in 1992.
Absolutely. His work was fundamental. He and his team were the ones who first nailed down the primary structures of crucial things like neurotransmitter receptors and ion channels.
So basically giving us the molecular blueprint for how parts of the brain actually function.
Exactly. It was groundbreaking stuff. And his lab, well, it became famous, maybe infamous, for churning out Nature papers throughout the 80s and early 90s.
It’s interesting. He really burst onto that world stage relatively late, around 1979 when he was already 50.
Yeah, but the impact afterwards was just immense. Now, we need to be clear about how we’re approaching this.
Right. We’re looking at anecdotal accounts, stories from people who actually worked there. And the sources themselves point out um that by today’s standards, Reiwa era standards, a lot of this would likely be seen as academic harassment.
Definitely. We’re not here to judge it by modern ethics necessarily, but to understand it, to report on the atmosphere as it was described.
Our mission, then, is to really get inside that intense environment. What drove this incredible productivity, this culture defined by Numa’s own words, “Effort is infinite.”
Let’s start there, with infinite effort. Because it wasn’t just a slogan, it was the lived reality.
A 24/7 expectation. Numa himself set the pace, didn’t he? Staying until 2:00 AM, sometimes even 5:00 AM.
Oh yeah. He lived it. And that meant everyone was expected to be available. Always. There’s this one story. A researcher gets a call. 6:00 AM Sunday morning.
Okay, must be an emergency, right? Yeah. Lab fire, contamination.
Nope. It’s Numa just casually asking for Pst I.
Pst I, that’s a restriction enzyme, right? Standard tool. He’s calling at 6:00 AM on a Sunday for that.
Exactly. It shows how blurred the lines were between work and, well, everything else. Even made-up holidays weren’t off-limits.
You mean like New Year’s?
Precisely. A staff member worked late on New Year’s Eve, took the first off, naturally. Then, on the afternoon of January 2nd, planning to head home, the phone rings.
Let me guess. Numa.
You got it. Asking, it’s already the 2nd, when are you coming back to the lab?
Wow. The implication is just brutal. Anytime off is slacking off.
It was seen as a lack of passion, a lack of dedication. And Numa even connected this dedication, this tension, as he called it, to physical health.
How so?
He claimed he personally never got colds because he maintained constant tension, which he believed made his body secrete ACTH, the stress hormone.
So stress keeps you healthy, that’s counterintuitive today.
Well, it fit his worldview. There’s an incident where someone was late because they had to go to the hospital for a cold. Numa’s reaction.
Let me brace myself.
He told them off saying, “You should not confuse public and private matters.” Illness was a private matter, interrupting the public duty of research.
So being physically present, demonstrating that effort, was paramount. It wasn’t just about the experiments.
Absolutely. He confronted one person who was just waiting by the phone for a collaborator’s call. Numa told him straight up, “I don’t feel any passion from you. I noticed you sometimes didn’t come to the lab on Saturdays and Sundays.”
It all comes back to that visible, relentless presence. Which logically leads to the next point, the demand for absolute rigor during that time.
Zero tolerance. For mistakes, for excuses, for anything less than perfection, really. And he established this from the moment you walked in.
Like that story about the new graduate student.
Yeah, incredible. The student was working with an enzyme that wasn’t very stable at room temperature, you know, only active for a few seconds.
Okay, a real technical challenge. Right.
And when the student mentioned this instability as a reason for maybe slower progress, Numa’s response wasn’t advice, it was, “Why don’t you quit graduate school?”
Just like that.
Quit. Just like that.
The message was clear: Find a way, or you don’t belong. Excuses weren’t part of the equation. If there’s a problem, infinite effort overcomes it.
And this applied even when technology seemed to offer a shortcut. Like with DNA sequencing.
Oh, absolutely. This was the era when sequence analysis software was coming in. But Numa insisted his team manually check every single nucleotide sequence the computer spat out.
Manually. Why?
His reason, “Computers make mistakes.” Yeah. He actually claimed that this painstaking manual double-checking was why his lab’s previous papers had zero errors.
So he’s directly linking this intense, almost paranoid methodology to their publication success. No trust, verify everything by hand.
It was about achieving absolute data integrity, which, you know, in cloning complex receptors, it’s critical. Mistakes could cost months or years.
That makes sense in a high-stakes environment. What about equipment failures? Things break down in labs?
Not an excuse. There’s the famous fraction collector incident. Machine stops overnight, the crucial active fractions are lost.
Okay, frustrating, but it happens. What did Numa say?
He demanded, “Why weren’t you watching it?” When the researcher said the machine failed, Numa shot back, “It’s natural for a fraction collector to fail. I always check it all night.”
He expected someone to literally watch a machine run all night long.
That was the implication. Perpetual vigilance. And he enforced this rhythm. Almost every night around 10:00 PM, he’d come down to the lab.
For what?
Daily progress reports. He wanted to know exactly what you did that day, and then he’d set specific, tough goals for the next day. No room to just coast.
It sounds incredibly hierarchical, almost military.
He even used that analogy. Apparently, when a colleague tried to push back even slightly, Numa’s response was chilling. He referenced the battlefield.
What did he say?
Something like, “I saw those who defied their superior’s orders on the battlefield. The next moment, their head was gone.”
Wow, that’s intense. But it raises a question, doesn’t it? Science is supposed to be about questioning, challenging assumptions. How did genuine breakthroughs happen under that kind of rigid authority?
That’s the paradox, maybe. The absolute compliance wasn’t necessarily about the ideas, perhaps, but about the execution. The elimination of error in the process. The data had to be perfect.
And that perfectionism, that rigor, carried right through to getting the work published.
Absolutely. Which brings us to what the researchers themselves called, the publication death match.
The death match. Sounds ominous.
And by all accounts it was. This was the final stage, writing the paper. It meant a two-to-three-week, one-on-one, intense session between Numa and the lead author.
One-on-one for weeks?
Yes. Often involving pulling multiple all-nighters in a row. And the feedback was brutal.
How brutal?
Authors were told their English was below middle school level, sometimes even preschool level. Manuscripts apparently got torn up in front of them.
After years of work on the research itself, that must have been crushing.
You’d think so. But Numa’s view was that the paper was the final product, the only thing the world sees. And the writing itself had this very peculiar method.
What was that?
He called it “English borrowing.” Basically, you were forbidden from writing original sentences, unless the finding was completely novel and required new phrasing.
So, how did you write?
You had to find established phrases, sentences used in top journals like Nature or Cell, written by native English speakers. And for every phrase you wanted to use, you had to provide Numa with multiple published examples.
So he was constantly asking, “Where’s the example? Show me where this was used before.”
Exactly. It was about minimizing any risk of awkward phrasing or grammatical error. Using language that was already validated, already accepted by the gatekeepers. Scientific precision applied to prose.
It’s like building with pre-approved blocks only.
Kind of, yeah. And the pressure wasn’t just on the writing, but the submission. He had this incredibly tight schedule.
For mailing a paper?
Yes. Specifically for Nature. To ensure the manuscript arrived in London by Thursday or Friday, making it into that week’s review batch, it had to be dropped off at the Osaka Central Post Office by 1:00 PM sharp on Tuesday.
Missing that deadline by an hour meant potentially losing a week’s lead on competitors.
That’s how he saw it. It was about controlling every variable, maximizing speed and competitive edge. Utter logistical control.
And this obsession with perfection extends to figures, illustrations, too.
Oh, absolutely. The story of the alignment figure is legendary. Numa would check figure dimensions with a ruler.
With a ruler? Seriously?
Seriously. They had this huge complex figure, B4 size, showing sequence alignments. After all the work, they found one single line was drawn solid when it should have been dashed.
Okay, a small error. Can’t they just fix it? White out, maybe?
Normally, yes, but Numa apparently hated correction fluid, forbade it. So the entire massive figure had to be redrawn from scratch.
Oh my god, for one dashed line.
And the story goes, the young secretary who made the mistake was so upset, her tears actually smudged the ink, making the redo absolutely necessary anyway.
The unbelievable pressure. Numa’s take on it captured his whole philosophy. “A paper is like a painting to a painter. You rewrite until you are satisfied. You must not lose power until the last stroke.”
So, let’s step back. We have this image of immense pressure, infinite effort, brutal critiques, but also incredible success. What was the core philosophy Numa tried to impart beyond just getting papers out?
Well, he really emphasized learning through doing. He’d say things like, “Knowledge from textbooks is important, but you must actually do experiments to gain living knowledge. It is more important to think while doing experiments.”
The less armchair theorizing, more getting your hands dirty.
Exactly. And he pushed people to aim high with their research topics, not just safe bets.
What did he advise there?
He told them, “Do work that is as important and meaningful as possible.” He apparently worried that younger researchers were playing it too safe, choosing projects that were easy to publish but didn’t tackle the big questions. He called it poking around in the corners of a heavy box.
He wanted them to try and lift the whole box.
Right. He believed scientists needed to take risks. He even compared it favorably to high-altitude climbing, arguing that, you know, research failure doesn’t actually cost a life.
That puts it in perspective. Did he have advice on timing those big, risky projects?
He did. He had this very specific idea. “A theme that is too early or too late compared to the flow of the world is not good. Choosing a theme that is half a step early ensures success.”
Half a step early. Not too far ahead, but just ahead of the curve.
Precisely. And you can see that in his own work, like the acetylcholine receptor cloning. It was a huge undertaking, right when the techniques became feasible and the field was ready for it. Landed him a Nature cover. Perfect timing.
His career really models that advice. High risk, perfectly timed, massive reward.
It does. And after all that intensity, all that demand, there is one quote that shows maybe a tiny sliver of understanding the human cost.
What’s that?
He apparently said, “A little alcohol is good. Sometimes you need it to bear the hardships of life.”
A rare concession to the pressure, maybe? So, looking back, we see this incredible engine of discovery. The Numa lab produced foundational work, changed neuroscience. But the anecdotes paint a picture of immense personal sacrifice demanded from everyone involved.
Exactly. And that’s the tension, isn’t it? Today, we rightly prioritize well-being, ethical treatment, work-life balance. These things are crucial. But Numa’s story, however extreme, poses a persistent question about what it takes to achieve truly transformative breakthroughs.
That relentless focus, that demand for absolute precision and unlimited effort on difficult, important problems.
It remains a benchmark, even if the methods are now unacceptable.
Tackling the very hardest questions often requires something beyond a standard nine-to-five commitment.
Numa himself said, “The most important thing I want to leave behind is the challenge to attempt something difficult.” So, thinking about that, and his idea that effort is infinite, where do you, listening now, draw the line?
How do you balance that necessary drive for excellence, for pushing boundaries in your own field, with the need to maintain a sustainable, whole life?
It’s the fundamental challenge, perhaps, for anyone aiming high. Where does that infinite effort stop? That’s something to think about.”
Constructing Research Questions: Doing Interesting Research (Mats Alvesson and Jorgen Sandberg 2024 SAGE Publications Ltd) Kindle版（電子書籍）7028円 ”a problematization methodology for identifying and challenging the assumptions underlying existing knowledge, and for generating research questions that can lead to more impactful theories.”（アマゾン書籍紹介より）
“Hi. Just checking in on your Kakenhi application. We’re a bit past the internal deadline now, and I don’t seem to have it yet. Just wanted to make sure everything’s okay.”
” I need to be direct. Your Kakenhi application is now overdue, and it’s starting to hold up the submission process for everyone else. I really need you to get it to me by the end of today.”
“Look, this is the final warning. Your application is now significantly overdue. If it is not on my desk by noon tomorrow, we are officially withdrawing it from the submission cycle. There are no exceptions.”
Joseph Goldberger’s Filth Parties A crusading doctor’s stomach-churning efforts to beat back pellagra in the American South. by Sam Kean September 8, 2020 Health & Medicinehttps://www.sciencehistory.org/stories/magazine/joseph-goldbergers-filth-parties/
Joseph Goldberger’s research on the prevention of pellagra Alfredo Morabia J R Soc Med. 2008 Nov 1;101(11):566–568. doi: 10.1258/jrsm.2008.08k010 https://pmc.ncbi.nlm.nih.gov/articles/PMC2586852/
The unwavering doctor who unraveled a medical mystery Sarah Schmitz 1,2,⁎, Eve J Lowenstein 1,2 https://pmc.ncbi.nlm.nih.gov/articles/PMC6451741/ Int J Womens Dermatol. 2018 Oct 17;5(2):137–139. doi: 10.1016/j.ijwd.2018.09.001
