盐酸丁丙诺啡(Buprenorphine Hydrochloride) - 药物靶点：κ opioid receptor x μ opioid receptor_在研适应症：阿片滥用，慢性疼痛，疼痛_专利_临床

概要

基本信息

简介盐酸丁丙诺啡（Buprenorphine Hydrochloride）是于1981年12月29日在美国获批上市，由Indivior公司生产。该药物的适应症为缓解疼痛，且疼痛程度足以需要使用阿片类镇痛剂，且其他治疗方法不足以缓解疼痛。其机制是通过作为μ-阿片受体的部分激动剂和κ-阿片受体的拮抗剂来发挥作用。在体外研究中，丁丙诺啡的一个特性是从受体中解离的速度非常缓慢。这可能是导致其作用时间比吗啡长、被阿片类拮抗剂逆转的不可预测性，以及其表现出低水平身体依赖性的原因。

药物类型

小分子化药

别名

BUP-XR、Buprenorphine hydrochloride (JP17/USP)、Buprenorphine Transdermal Patch

+ [38]

靶点

κ opioid receptor x μ opioid receptor

作用方式

拮抗剂、激动剂

作用机制

κ opioid receptor拮抗剂(κ-阿片受体拮抗剂)、μ opioid receptor激动剂(μ-阿片受体激动剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Knight Therapeutics, Inc.

Paladin Labs, Inc.RB Pharmaceuticals Ltd.

+ [6]

非在研机构

Purdue Pharma LP

The University of California, San Francisco

河北立生药业集团有限公司

+ [12]

权益机构

Purdue Pharma LPL. MOLTENI & C. DEI FRATELLI ALITTI - SOCIETA DI ESERCIZIO - S.P.A.Accord Healthcare, Inc. (Canada)

+ [7]

最高研发阶段批准上市

首次获批日期

美国 (1981-12-29),

疼痛

最高研发阶段(中国)撤市

特殊审评孤儿药 (美国)

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结构/序列

分子式C29H42ClNO4

InChIKeyUAIXRPCCYXNJMQ-RZIPZOSSSA-N

CAS号53152-21-9

关联

348

项与盐酸丁丙诺啡相关的临床试验

NCT07485335

/ Not yet recruiting临床4期IIT

Implementation and Effectiveness Testing of a Bundled Post-Hospital Intervention for Non-fatal Opioid Overdoses

Opioid overdose deaths have reached historically high records in the United States and are particularly concentrated among patients after emergency department (ED) discharge. Evidence-based treatment modules to reduce repeat opioid overdose and mortality are lacking in this patient population. A bundled intervention is proposed, including telehealth, peer support specialist, buprenorphine, and linkage for definitive care, that is designed to increase treatment uptake in this patient population post-ED discharge, reduce repeat opioid overdoses, and end overdose deaths.

开始日期2026-09-07

申办/合作机构

The University of Alabama at Birmingham

[+1]

NCT07469501

/ Not yet recruiting临床4期IIT

Improving Buprenorphine Initiation Among Individuals With Opioid Use Disorder Using Fentanyl

The goal of this pragmatic randomized controlled trial is to compare treatment outcomes of two strategies for initiating buprenorphine treatment (low-dose initiation and direct-to-inject) in adults with opioid use disorder (OUD) who use fentanyl. This study aims to:
1. Compare effectiveness of each strategy on treatment retention in a real world, clinical setting, and
2. Assess differences between strategies in patient-reported outcomes, including withdrawal symptoms, cravings, drug use, treatment satisfaction, and overall acceptability.
Participants will:
1. Be randomized to initiate buprenorphine via a low-dose initiation or direct-to-inject protocol at an outpatient buprenorphine clinic,
2. Keep a diary of craving and withdrawal symptoms for the first 7 days after initiation, and
3. Visit the outpatient clinic 7, 30, and 90 days after initiation for urinary drug screen and follow-up surveys.

开始日期2026-06-01

申办/合作机构

The University of California, San Francisco

[+2]

NCT07430345

/ Not yet recruiting临床1/2期IIT

Buprenorphine for Analgesia in Older Adults With Acute Fractures in the Emergency Department: a Randomized Controlled Study

The goal of this clinical trial is to learn if buprenorphine can treat pain in older adults who have broken bones. The main questions it aims to answer are:
Is buprenorphine as effective as opioids to treat pain? Are there less side effects with buprenorphine? Researchers will compare buprenorphine and hydromorphone to see if there are differences in pain control and side effects.
Participants will be given one of the two study drugs after breaking a bone and asked about their pain scores and side effects for the next 48 hours.

开始日期2026-04-01

申办/合作机构

The Cooper Health System, Inc.

100 项与盐酸丁丙诺啡相关的临床结果

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100 项与盐酸丁丙诺啡相关的转化医学

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100 项与盐酸丁丙诺啡相关的专利（医药）

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4,192

项与盐酸丁丙诺啡相关的文献（医药）

2026-03-01·Journal of substance use and addiction treatment

Real-world longitudinal treatment trajectories following opioid use disorder diagnosis among commercially insured beneficiaries in the United States

Article

作者: Johnson, Abree ; Rizk, John G ; Saini, Jannat ; Ehret, Megan ; Qato, Danya M ; Pathan, Uzma ; DiPaula, Bethany ; Li, Yujia

INTRODUCTION:

Early initiation and continuity of treatment are critical for the effective management of opioid use disorder (OUD). Despite the availability of effective medications for OUD (MOUD), many individuals never initiate treatment, and those who do often discontinue early. A better understanding of real-world treatment patterns is needed to inform strategies for improved long-term engagement in care. This study uses a novel technique to characterize and visualize real-world treatment trajectories following an OUD diagnosis among commercially insured individuals.

METHODS:

Retrospective, longitudinal descriptive study utilizing claims data from the IBM MarketScan® (now Merative^TM) commercial and Medicare Supplemental and Coordination of Benefits Databases, from 2010 to 2019. The study included beneficiaries aged 18-85 years with an OUD diagnosis, requiring continuous insurance enrollment for at least 6 months before and 3 months after the first date of OUD diagnosis (index date). Beneficiaries with any prescription or medical service claims for MOUD or with OUD remission codes during the 6-month baseline period were excluded. Initial OUD treatment was assessed in the 3-month period after the index date (treatment assignment period). Beneficiaries were categorized into 8 groups based on treatment receipt during the treatment assignment period: behavioral therapy (BH) only, buprenorphine (BUP), buprenorphine with behavioral therapy (BUP + BH), naltrexone (NTX), naltrexone with behavioral therapy (NTX + BH), methadone with or without behavioral therapy (MTD+/-BH), no treatment, and all other treatment combinations. Monthly treatment assignments, including disenrollment, were summarized into trajectories during the subsequent 9-month follow-up period. Sankey diagrams were used to visualize monthly transitions between treatment states and quantify the number of beneficiaries in each trajectory.

RESULTS:

The study identified 339,224 beneficiaries with an OUD diagnosis and 22,902 distinct treatment trajectories. The most common treatment assignment period category was BH only, with 75.5 % of beneficiaries, while 14.1 % of beneficiaries were in a category that included any MOUD. Treatment continuity was highest among those starting with MTD+/-BH, and lowest among those NTX with or without BH. Overall, high disenrollment rates were observed regardless of treatment assignment, especially early in the follow-up period.

CONCLUSIONS:

Findings highlight a significant discordance between real-world treatment patterns and evidence-based guidelines for OUD treatment.

2026-03-01·ENVIRONMENTAL TOXICOLOGY

Ecotoxicological Evaluation of the Antimicrobial Butylparaben in Edaphic Organisms Using Multiple Biomarkers

Article

作者: Junior, Osvaldo Valarini ; de Souza, Cassiano Aparecido ; Downs, Craig Allan ; Peron, Ana Paula ; Scapin, Diane ; Tsubouchi, Lorena Maihury Santos ; Santo, Diego Espirito ; de Almeida, Edson Araújo ; Maehashi, Ana Elisa ; Düsman, Elisângela ; Gonzalez, Regiane da Silva ; Oliveira, Anna Karolina Gomes ; Tractz, Gideã Taques ; Henrich, Carmem Lúcia

ABSTRACT:

Butylparaben (BuP) recurrently contaminates soils worldwide, mainly by incorporating sewage sludge into cultivated areas, using wastewater in irrigation, and leaching contaminated soils. However, there are few studies on the ecotoxicological effects of this paraben on edaphic organisms. The ecotoxicity of BuP was evaluated in seeds of Daucus carota , Allium cepa , and Cucumis sativus , in the roots of A. cepa bulbs, and in Eisenia fetida earthworms, at concentrations of 10, 50, 100, and 500 ng/L. In root meristems, the four concentrations of BuP induced lipid peroxidation and raised the levels of superoxide radicals, which triggered inhibition of cell division and mitotic spindle alteration, significantly reducing the growth of roots in seeds and bulbs. In animals, BuP at 10, 50, 100, and 500 ng/L caused 80%, 80%, 70%, and 90% evasion of earthworms from artificial soil, respectively. In addition, this paraben did not cause mortality in earthworms after 14 days of exposure. However, all concentrations increased the production of superoxide and hydroxyl radicals in cells and caused lipid peroxidation. Thus, increased exposure to this compound can affect the ecological functions negatively and/or cause the death of these animals. Therefore, recurrent contamination with BuP can negatively impact soil quality, posing a risk to agricultural productivity and the environment. This study is a pioneer in the ecotoxicological evaluation of BuP in plants at environmentally relevant concentrations and in the behavioral and oxidative stress study in earthworms.

2026-03-01·ACADEMIC EMERGENCY MEDICINE

Drug Use After Emergency Department‐Initiated Injectable Buprenorphine: A Secondary Analysis of the ED ‐ INNOVATION Ancillary Safety and Feasibility Trial

Article

作者: Phadke, Manali ; McCormack, Ryan ; D'Onofrio, Gail ; Fiellin, David A. ; Perrone, Jeanmarie ; Anderson, Erik ; Herring, Andrew ; Dziura, James ; Samuels, Elizabeth A. ; Hawk, Kathryn ; Cowan, Ethan

ABSTRACT:

Study Objective:

To characterize opioid and nonopioid drug use in the week following emergency department (ED)‐initiated extended‐release buprenorphine (XR‐BUP) treatment using both self‐reported data and urine drug screens (UDS).

Methods:

This study uses data collected during a nonrandomized clinical trial of patients with untreated opioid use disorder (OUD), testing the safety and feasibility of initiating XR‐BUP in patients presenting with minimal to mild withdrawal. The study was conducted from July 2020 to May 2023 across four urban academic EDs in the Northeast, Mid‐Atlantic, and Pacific regions of the United States. A total of 100 participants, 18 years or older with OUD defined by DSM‐5 criteria, a clinical opiate withdrawal scale (COWS < 8), and a positive opioid urine screen were included. Individuals with recent MOUD treatment, presentation for overdose, or concurrent methadone use were excluded. All participants received a single subcutaneous injection of 24 mg XR‐BUP (CAM2038) during their ED visit. The primary outcomes were self‐reported daily opioid and nonopioid drug use over 7 days postinjection using daily Qualtrics surveys and UDS results on day 7.

Results:

Among participants who received XR‐BUP and completed daily surveys, 98% reported at least one opioid‐free day, and 63% reported no opioid use across all 7 days. Day 7 UDS results showed decreased detection of opioids, stimulants, and benzodiazepines. Reported polysubstance use also declined over the observation period.

Conclusions:

ED‐initiated XR‐BUP was associated with substantial reductions in opioid and polysubstance use during the first week post‐discharge, supporting its role in early overdose risk mitigation and highlighting its value as an ED‐based intervention for opioid use disorder.

Trial Registration:

ClinicalTrials.gov Identifier: NCT03658642

366

项与盐酸丁丙诺啡相关的新闻（医药）

2026-03-20

·搜狐新闻

CCR4：免疫治疗与炎症干预的核心靶点

1. CCR4靶点概述：生理功能与病理调控的核心作用 C-C 趋化因子受体 4（CCR4）是 G 蛋白偶联受体家族的重要成员，主要参与免疫细胞的募集、迁移及功能调控。作为 Th2 细胞和调节性 T 细胞（Regulatory T cells, Treg）的关键表面受体之一，CCR4 通过识别其配体 CCL17（TARC）和 CCL22（MDC），在免疫稳态维持、炎症反应及免疫耐受形成过程中发挥重要作用。近年来的研究表明，CCR4 的异常表达或功能失衡与多种疾病密切相关，尤其在血液系统恶性肿瘤、实体瘤、自身免疫性疾病及慢性炎症性疾病中表现突出。CCR4 不仅通过募集免疫抑制性 Treg 改变局部免疫微环境，还可直接参与肿瘤细胞迁移、侵袭及耐药调控。随着 CCR4 靶向抗体、小分子拮抗剂及细胞治疗策略的不断推进，该受体已成为免疫治疗和炎症干预领域的重要研究靶点。2. CCR4的分子结构与配体互作机制 CCR4 是一种典型的七次跨膜 G 蛋白偶联受体，主要表达于 Th2、Treg、树突状细胞、巨噬细胞及细胞因子诱导杀伤细胞等多种免疫细胞表面 [4–7]。在健康个体中，CCR4 常被视为 Th2、Th17 和 Treg 细胞的重要标志物 [4]，而在多种肿瘤细胞中，其异常表达与不良预后密切相关 [8–10]。CCR4 的主要配体为 CCL17（TARC）和 CCL22（MDC），二者由树突状细胞和巨噬细胞等多种细胞产生，通过募集 CCR4 阳性免疫细胞在炎症及肿瘤微环境中发挥重要调控作用 [6–8]。在肿瘤微环境中，M2 型巨噬细胞可显著增强 CCL17 的分泌，进而促进肿瘤细胞的迁移、侵袭及干性维持 [8]。配体-受体结合后，CCR4 可激活多条信号通路，并在不同细胞类型和疾病背景下呈现出显著的功能多样性。3. CCR4信号通路解析：免疫调控与疾病进展的分子基础3.1 G 蛋白依赖性信号通路 CCR4 主要通过 Gαi 蛋白介导下游信号转导。配体结合后，Gβγ 亚基可激活 Rho 激酶和 p38 MAPK 通路，调控细胞骨架重排、趋化迁移及炎症反应 [13]。此外，在不同病理环境中，CCR4 还可通过 PI3K/AKT 等信号通路影响细胞存活、代谢及耐药性 [11,12]。3.2 G 蛋白非依赖性信号及偏向性激动 β-arrestin2 在 CCR4 信号转导中具有重要作用，既参与受体内吞，又可介导独立的信号级联反应。在过敏性炎症模型中，CCL22-CCR4-β-arrestin2 轴被证实在 Th2 细胞趋化和炎症加重中发挥关键作用 [13]。不同配体在特定细胞环境下可能呈现偏向性信号激活模式，为靶向干预提供了新的思路 [14]。3.3 CCR4 在免疫细胞迁移与功能中的作用 CCR4 是 Th2 细胞和 Treg 细胞趋化的重要调控因子。在肿瘤微环境中，CCR4⁺ Treg 的富集与免疫抑制和不良预后密切相关 [15]。此外，CCR4 还参与 CIK 细胞、树突状细胞及巨噬细胞功能调控，在抗肿瘤免疫、炎症反应及免疫耐受形成中呈现双重作用。3.4 CCR4 调控的其他生物学过程 CCR4 通过 ERK/AKT、EZH2-DNMT3A 等多条通路调控肿瘤细胞迁移、侵袭、上皮-间质转化及耐药过程 [3,8,16]，进一步凸显其在肿瘤进展中的核心地位。3.5 CCR4 与其他趋化因子受体的协同与差异在胸腺发育和中枢耐受建立过程中，CCR4 与 CCR7 在不同阶段和细胞亚群中发挥互补作用，共同确保自身反应性 T 细胞的有效清除 [17]。4. CCR4在多系统疾病中的致病机制：肿瘤、自身免疫病及其他适应症4.1 血液系统恶性肿瘤 CCR4 在多种 T 细胞来源的血液系统恶性肿瘤中高度表达，尤其在成人 T 细胞白血病/淋巴瘤（ATL）和皮肤 T 细胞淋巴瘤（CTCL）中具有明确的病理学意义。CCR4⁺ 肿瘤细胞可通过其配体 CCL17 和 CCL22 实现定向迁移和组织浸润，同时逃避免疫监视。临床研究显示，CCR4 的高表达通常与疾病进展、侵袭性增强及不良预后密切相关。基于这一特征开发的人源化抗 CCR4 单克隆抗体 Mogamulizumab，通过抗体依赖的细胞介导细胞毒作用（ADCC）有效清除 CCR4⁺ 肿瘤细胞，并可同时耗竭免疫抑制性的 Treg，从而改善抗肿瘤免疫反应 [2,18]。该药物已获批用于复发或难治性 CTCL 和外周 T 细胞淋巴瘤，验证了 CCR4 作为治疗靶点的临床可行性。4.2 实体瘤除血液系统肿瘤外，CCR4 在多种实体瘤中同样发挥重要作用，包括肝细胞癌、肺腺癌、乳腺癌及结直肠癌等。研究发现，肿瘤相关巨噬细胞和树突状细胞可分泌大量 CCL17 和 CCL22，选择性募集 CCR4⁺ Treg 至肿瘤微环境，导致局部免疫抑制并削弱抗肿瘤免疫应答 [8,15]。此外，部分实体瘤细胞本身亦表达 CCR4，其激活可通过 PI3K/AKT、ERK 等信号通路促进肿瘤细胞增殖、迁移和上皮-间质转化，从而增强侵袭性和转移潜能 [3,8]。这些发现为 CCR4 靶向治疗在实体瘤中的应用提供了理论基础，并推动了 CCR4 拮抗剂与免疫检查点抑制剂联合治疗策略的探索 [19,20]。4.3 炎症性与自身免疫性疾病 CCR4 在炎症性和自身免疫性疾病中的作用主要与 Th2 和 Treg 细胞迁移密切相关。在类风湿关节炎、特应性皮炎及系统性红斑狼疮等疾病中，CCR4-CCL17/CCL22 轴的异常激活可导致免疫细胞在靶组织中过度聚集，从而加重炎症反应和组织损伤 [1]。在部分疾病背景下，CCR4⁺ Treg 的募集可能具有双重作用：一方面有助于抑制过度炎症，另一方面在慢性炎症状态下可能促进免疫失衡并延缓组织修复。这种功能的情境依赖性也提示 CCR4 靶向干预需充分考虑疾病阶段和免疫状态。4.4 代谢相关疾病近年来，CCR4 在代谢性疾病中的作用逐渐受到关注。在肥胖及其相关并发症中，CCR4 及其配体与脂肪组织慢性低度炎症、血管内皮功能障碍密切相关。CCR4 介导的免疫细胞募集可能参与胰岛素抵抗和代谢紊乱的发生过程，为炎症-代谢交叉调控机制提供了新的研究视角。4.5 病毒感染相关疾病在 HTLV-1 和 HIV-1 感染中，CCR4⁺ CD4⁺ T 细胞被认为是重要的病毒储存库。CCR4 的高表达不仅与病毒持续存在相关，还可能影响免疫重建和疾病进展 [4,21]。这些发现提示，CCR4 在病毒感染相关免疫病理过程中具有潜在的干预价值。4.6 神经性疼痛动物实验研究表明，CCR4 及其配体在神经性疼痛的发生发展中发挥调控作用。CCR4 拮抗剂可显著缓解疼痛行为，并增强阿片类镇痛药物的疗效 [22]，为慢性疼痛的多靶点联合治疗提供了新的研究方向。5. CCR4靶向药物研发进展：已上市药物与在研管线全景近年来，靶向CCR4的药物研发取得了显著进展，涵盖了从单克隆抗体、小分子化药到CAR-T细胞疗法等多种药物类型。其中，莫格利珠单抗作为CCR4拮抗剂的代表药物，已在菌样真菌病、塞扎里综合征及外周T细胞淋巴瘤等适应症中获得批准上市。其他在研药物如Tivumecirnon Besylate、Autologous CCR4 CAR T cells等正处于临床2期和1期阶段，主要针对转移性胃癌、晚期癌症及T细胞淋巴瘤等恶性肿瘤。此外，多个临床前研究项目正在探索CCR4拮抗剂在脓毒症、肝癌、哮喘、鼻炎、贫血及脑卒中等多种疾病中的潜力。总体来看，CCR4靶向药物的研发呈现出多样化的发展趋势，肿瘤仍是主要研究方向，同时也在向其他疾病领域拓展。（数据截止到2026年3月11日，来源于synapse）6. CCR4研究工具推荐：重组蛋白与抗体产品选型指南华美生物提供CCR4重组蛋白、抗体产品，助力您进行相关机制研究及靶向药物开发。● CCR4 重组蛋白Recombinant Human C-C chemokine receptor type 4 (CCR4)-VLPs (Active); CSB-MP004843HURecombinant Human C-C chemokine receptor type 4 (CCR4) (Active); CSB-CF004843HU● CCR4 抗体CCR4 Recombinant Monoclonal Antibody; CSB-RA004843MA01HUCCR4 Antibody; CSB-PA004843LA01HU参考文献：[1] Kayoko Hase, K. Tani, Teruki Shimizu, Y. Ohmoto, K. Matsushima, S. Sone.(2001). Increased CCR4 expression in active systemic lupus erythematosus.[2] Kenji Ishitsuka, Tomoharu Yasukawa, Yukie Tsuji.(2024). Safety and effectiveness of mogamulizumab in relapsed or refractory CC chemokine receptor 4‐positive peripheral T‐cell lymphoma and relapsed or refractory cutaneous T‐cell lymphoma: A post‐marketing surveillance in Japan.[3] Xi Cheng, Huo Wu, Zhi-Jian Jin, Ding Ma, Stanley Yuen, Xiaoqian Jing, Minmin Shi, B. Shen, C. Peng, R. Zhao, Wei-hua Qiu.(2017). Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior.[4] Y. Yamano, N. Araya, Tomoo Sato, A. Utsunomiya, Kazuko Azakami, D. Hasegawa, Toshihiko Izumi, Hidetoshi Fujita, S. Aratani, N. Yagishita, Ryoji Fujii, K. Nishioka, S. Jacobson, T. Nakajima.(2009). Abnormally High Levels of Virus-Infected IFN-γ+CCR4+CD4+CD25+ T Cells in a Retrovirus-Associated Neuroinflammatory Disorder.[5] C. Carola, Andrew Salazar, C. Rakers, F. Himbert, Q. Do, P. Bernard, Joerg von Hagen.(2021). A Cornflower Extract Containing N-Feruloylserotonin Reduces Inflammation in Human Skin by Neutralizing CCL17 and CCL22 and Inhibiting COX-2 and 5-LOX.[6] Yongjian Dong, Shuhui Gao, Xue-fang Zhang, Jing Kou, Jing Liu, Ting Ye, Han Shen.(2021). CCL17 and CCL22 induce CCR4 receptor expression and promote cytokine-induced killer cells migration.[7] Inés Lecoq, K. Kopp, M. Chapellier, Panagiotis Mantas, E. Martinenaite, Maria Perez-Penco, Lars Rønn Olsen, M. Zocca, A. Wakatsuki Pedersen, M. Andersen.(2022). CCL22-based peptide vaccines induce anti-cancer immunity by modulating tumor microenvironment.[8] Chun Jin, Liangliang Lu, Jian Gao, Ling Chen.(2024). M2-like Macrophages-derived CCL17 Promotes Esophageal Squamous Cell Carcinoma Metastasis and Stemness via Activating CCR4-mediated ERK/PD-L1 Pathway..[9] A. Maolake, K. Izumi, K. Shigehara, Ariunbold Natsagdorj, H. Iwamoto, S. Kadomoto, Yuta Takezawa, Kazuaki Machioka, K. Narimoto, M. Namiki, Wen-Jye Lin, Guzailinuer Wufuer, A. Mizokami.(2016). Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22–CCR4 axis.[10] W. Gan, Baoye Sun, Zhangfu Yang, Cheng Ye, Zhutao Wang, Cheng Zhou, Guo-Qiang Sun, Yong Yi, Shuang-Jian Qiu.(2024). Enhancing hepatocellular carcinoma management: prognostic value of integrated CCL17, CCR4, CD73, and HHLA2 expression analysis.[11] Lichao Zhang, Xiaoqing Lu, Yuanzhi Xu, Xiaoqin La, Jinmiao Tian, Aiping Li, Hanqing Li, Changxin Wu, Yanfeng Xi, Guisheng Song, Zhaocai Zhou, Wenqi Bai, Liwei An, Zhuoyu Li.(2023). Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22–CCR4–ATF6–GRP78 axis.[12] Shuixiang Deng, Peng Jin, P. Sherchan, Shengpeng Liu, Yuhui Cui, Lei Huang, John H. Zhang, Ye Gong, Jiping Tang.(2021). Recombinant CCL17-dependent CCR4 activation alleviates neuroinflammation and neuronal apoptosis through the PI3K/AKT/Foxo1 signaling pathway after ICH in mice.[13] Rui Lin, Y. Choi, David A Zidar, Julia K. L. Walker.(2018). β‐Arrestin‐2‐Dependent Signaling Promotes CCR4‐mediated Chemotaxis of Murine T‐Helper Type 2 Cells.[14] H. Lim, J. R. Lane, Meritxell Canals, M. Stone.(2021). Systematic Assessment of Chemokine Signaling at Chemokine Receptors CCR4, CCR7 and CCR10.[15] Tania Sarkar, Subhanki Dhar, D. Chakraborty, Subhadip Pati, S. Bose, A. Panda, Udit Basak, S. Chakraborty, S. Mukherjee, A. Guin, Kuladip Jana, Diptendra K. Sarkar, Gaurisankar Sa.(2022). FOXP3/HAT1 Axis Controls Treg Infiltration in the Tumor Microenvironment by Inducing CCR4 Expression in Breast Cancer.[16] Li Zhang, Sijuan Tian, Jie Chang, Shimin Quan, Ting Yang, Minyi Zhao, Li Wang, Xiaofeng Yang.(2024). Activation of the CCL22/CCR4 causing EMT process remodeling under EZH2-mediated epigenetic regulation in cervical carcinoma.[17] Y. Li, J. Srinivasan, Hilary J. Selden, Lauren I. R. Ehrlich.(2023). CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.[18] Z. Marušić, E. Calonje.(2021). Skin adnexal tumours in a tertiary dermatopathology service.[19] Do-Youn Oh, Min-Hee Ryu, Jun-Eul Hwang, Jaeyong Cho, D. Y. Zang, Sang Cheul Oh, J. Lee, Keun-Wook Lee, S. Rha, B. Shim, William Ho, M. Chisamore, Paul Dong Rhee, Sooa Jung, Taewan Kim, Jiyeon Yoon, Hosung Jang, E. Baek, Young-Su Noh.(2025). A phase 2 study to assess the safety and efficacy of FLX475 (tivumecirnon) combined with pembrolizumab in patients with advanced or metastatic gastric cancer..[20] Adam Grant, Juraj Adamik, Jingtao Qiu, Jacob Wert, Molly Grandcolas, S. Jacobson, R. Goyal, William Ho, Shoji Ikeda, Marvin Au, Damian L Trujillo, M. Chisamore, D. Nagata, M. S. Ghomi, D. Brockstedt, P. Kassner, George E. Katibah.(2024). Abstract 2485: A combined mregDC and Treg signature associates with antitumor efficacy of CCR4 antagonist tivumecirnon FLX475.[21] Y. Mahnke, K. Fletez-Brant, I. Sereti, M. Roederer.(2016). Reconstitution of Peripheral T Cells by Tissue-Derived CCR4+ Central Memory Cells Following HIV-1 Antiretroviral Therapy.[22] J. Bogacka, Katarzyna Ciapała, K. Pawlik, K. Kwiatkowski, J. Dobrogowski, A. Przeklasa-Muszyńska, J. Mika.(2020). CCR4 Antagonist (C021) Administration Diminishes Hypersensitivity and Enhances the Analgesic Potency of Morphine and Buprenorphine in a Mouse Model of Neuropathic Pain.返回搜狐，查看更多

免疫疗法细胞疗法

2026-03-20

·生物制品圈

豪掷 6.5 亿，科尔吉姆加码 ADHD 赛道

摘要：科尔吉姆制药近日宣布以 6.5 亿美元预付款收购科里姆旗下 ADHD 药物 Azstarys，另含 1.35 亿美元潜在里程碑付款，交易预计 2026 年二季度完成。此次收购让科尔吉姆拥有 Jornay PM 与 Azstarys 两款差异化 ADHD 药物，可直接复用现有 ADHD 商业运营体系。Azstarys 作为独家速释 + 长效一体胶囊，市场排他期至 2037 年，公司预计其 2026 年下半年营收超 5000 万美元，这笔交易也让科尔吉姆的药品管线更趋多元。大手笔现金出手，锁定独家 ADHD 药坦白讲，科尔吉姆这次在 ADHD 赛道的出手相当果断。3 月 19 日的公告里，这家马萨诸塞州药企直接砸出 6.5 亿美元预付款，从科里姆手中拿下了 Azstarys 的全部权益，还有一笔 1.35 亿美元的里程碑付款，视药物后续表现而定。这笔交易的核心标的 Azstarys，算得上市面上独一份的 ADHD 药。2021 年 FDA 批准上市后，它就成了首个也是唯一一个将速释和长效成分融合在单粒胶囊里的中枢神经兴奋剂，适配 6 岁及以上患者。科尔吉姆直言，这款药的市场排他期能延续到 2037 年，单看时间维度，就有足够的市场操作空间。科里姆从未公开过 Azstarys 的销售数据，但科尔吉姆对它的营收预期很明确：2026 年下半年，营收能突破 5000 万美元。其实单看这款药的剂型设计，就能理解公司的底气，毕竟在 ADHD 用药里，兼顾快速起效和长效持效的产品，本就不多。两款药形成互补，处方量已有基础拿下 Azstarys 后，科尔吉姆的 ADHD 产品线就凑齐了两款核心产品。2024 年，它曾以 5.25 亿美元收购艾恩肖制药，将 Jornay PM 收入囊中，这款药 2025 年的销售额达到 1.49 亿美元，仅四季度就贡献了 4600 万美元，市场排他期至 2032 年。有意思的是，这两款药的用药逻辑完全不同，刚好能形成互补。Jornay PM 是目前唯一一款睡前服用的 ADHD 药，晨起就能起效，全天不用补服，更适合需要长期规律用药的儿童和青少年。Azstarys 则是晨起服用，快速起效后能持续一整天，科尔吉姆的商务负责人直言，成年 ADHD 患者更偏爱这款药的用药方式。去年一年，两款药的处方量都突破了 76 万张。要知道，现在 ADHD 市场还是仿制药的天下，品牌药能拿到这个处方量，已经算不错的成绩。而且市场调研的数据很扎心，ADHD 患者平均要试三款药，才能找到适合自己的，选药难的痛点，其实就是品牌药的机会。借力现有基建，管线多元再提气科尔吉姆能敢花大价钱收 Azstarys，底气还来自于它已经搭好的 ADHD 商业体系。公司 CEO 在电话会议里说，Azstarys 能直接复用现有的销售和渠道资源，不用再重新搭建团队，这就把收购后的整合成本压到了最低。某种程度上，这笔收购也是科尔吉姆对自身管线的一次补位。在此之前，公司的核心业务是疼痛管理，Belbuca、Xtampza ER 和 Nucynta 三款止痛药 2025 年的销售额都在 1.96 亿至 2.22 亿美元之间，营收结构相对单一。现在加上两款 ADHD 药，公司的营收支柱就多了一根。市场对这笔交易的反应也很直接，公告发布后，科尔吉姆的股价小幅上涨 4.31%。只是 ADHD 市场的竞争从来都不弱，仿制药的价格优势摆在那里，科尔吉姆想靠两款差异化产品抢占更多市场，后续的市场推广节奏，才是关键。目前，这笔收购还在走流程，科尔吉姆和科里姆都预计能在 2026 年二季度完成交割。至于 Azstarys 能不能达到公司的营收预期，两款药能不能真正撬动仿制药主导的 ADHD 市场，还得看市场的实际反馈。参考来源：https://www.fiercepharma.com/pharma/collegium-ponies-650m-gain-adhd-drug-azstarys-corium 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

2026-03-20

·drugs

Injectable, Extended-Release Buprenorphine Feasible for Opioid Use Disorder During Pregnancy

FRIDAY, March 20, 2026 -- Injectable, extended-release buprenorphine is safe and effective in pregnant women with opioid use disorder (OUD), according to a study published online March 16 in JAMA Internal Medicine . T. John Winhusen, Ph.D., from the University of Cincinnati, and colleagues evaluated the effectiveness and safety of extended-release buprenorphine versus sublingual buprenorphine for OUD in pregnancy through 12 months postpartum. The analysis included 140 adults with OUD and a singleton pregnancy of 6 to 30 weeks of gestational age seen at 13 outpatient cross-disciplinary peripartum OUD treatment sites. The researchers found that illicit opioid abstinence was higher during pregnancy for participants randomly assigned to extended-release versus sublingual buprenorphine (82.5 versus 72.6 percent). The groups were similar with respect to postpartum abstinence rates (60.2 versus 59.5 percent). There were fewer serious adverse events during pregnancy (8.7 versus 26.8 percent) and postpartum (6.0 versus 18.6 percent) among those receiving extended-release buprenorphine. There were more nonserious adverse events deemed medication-related for extended-release participants during pregnancy (26.1 versus 7.0 percent). Infants did not differ in the need for opioid treatment based on mothers' treatment assignment to extended-release versus sublingual buprenorphine (30.2 versus 26.5 percent; relative risk, 1.14; 98 percent confidence interval, 0.54 to 1.99; P = 0.64). "We knew that injectable extended-release buprenorphine leads to superior rates of illicit opioid abstinence in nonpregnant adults, but there had been no completed randomized clinical trial testing its use during pregnancy," Winhusen said in a statement. "It is exciting to share the results of this trial, which have immediate clinical application: this longer-acting medication can safely and more effectively support treatment and recovery in pregnant patients." Several authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text

临床结果临床研究

100 项与盐酸丁丙诺啡相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00836	盐酸丁丙诺啡	N07BC01 N02AE01	DB00921

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
阿片滥用	加拿大	Knight Therapeutics, Inc.	2018-04-18
慢性疼痛	加拿大	Paladin Labs, Inc.	2017-06-21
鸦片依赖	比利时	RB Pharmaceuticals Ltd.	1999-11-02
鸦片依赖	塞浦路斯	RB Pharmaceuticals Ltd.	1999-11-02
鸦片依赖	捷克	RB Pharmaceuticals Ltd.	1999-11-02
鸦片依赖	法国	RB Pharmaceuticals Ltd.	1999-11-02
鸦片依赖	拉脱维亚	RB Pharmaceuticals Ltd.	1999-11-02
鸦片依赖	立陶宛	RB Pharmaceuticals Ltd.	1999-11-02
鸦片依赖	卢森堡	RB Pharmaceuticals Ltd.	1999-11-02
鸦片依赖	葡萄牙	RB Pharmaceuticals Ltd.	1999-11-02
物质相关疾病	中国	青海制药厂	1994-01-01
麻醉	日本	Otsuka Pharmaceutical Co., Ltd.	1983-05-27
癌症疼痛	日本	Otsuka Pharmaceutical Co., Ltd.	1983-05-27
术后疼痛	日本	Otsuka Pharmaceutical Co., Ltd.	1983-05-27
疼痛	美国	Indivior, Inc.	1981-12-29

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
神经痛	临床3期	美国	BioDelivery Sciences International, Inc.	2011-03-01
椎间盘疾病	临床3期	中国	萌蒂（中国）制药有限公司	2009-08-01
海洛因依赖	临床3期	美国	Indivior, Inc.	2009-05-01
阿片类药物依赖美沙酮	临床3期	美国	Titan Pharmaceuticals, Inc.	2006-10-01
腰痛	临床3期	日本	Mundipharma KK	2006-05-01
脊椎骨关节炎	临床3期	美国	Purdue Pharma LP	2004-01-01
阿片相关性障碍	临床3期	美国	University of California, Los Angeles	2003-06-01
2型糖尿病	临床3期	美国	Purdue Pharma LP	2003-04-01
骨关节炎	临床3期	美国	Purdue Pharma LP	2003-04-01
疼痛障碍	临床3期	美国	Purdue Pharma LP	2001-03-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05118204 (Micro-bupe, CTgov)	临床4期	阿片相关性障碍 \| 阿片滥用 \| 慢性疼痛 ... 更多	23	BUP microdose induction+Linkage to outpatient BUP treatment (BUP Microdose Induction)	鑰齋獵膚構鏇餘襯廠蓋 = 範壓艱襯顧蓋願築鹽鹽憲鑰鹽鹹製蓋廠積製襯 (衊淵鑰網遞築艱簾網淵, 膚簾夢觸齋願鬱構膚願 ~ 願餘憲齋艱淵淵衊鏇齋) 更多	-	2025-10-31
				TAU (Treatment As Usual (TAU))	鑰齋獵膚構鏇餘襯廠蓋 = 顧鬱夢鏇觸積鏇鏇觸齋憲鑰鹽鹹製蓋廠積製襯 (衊淵鑰網遞築艱簾網淵, 鑰獵蓋窪觸衊憲壓網構 ~ 獵鹽齋築糧壓範獵糧願) 更多
Pubmed 人工标引	N/A	阿片相关性障碍	-	BUP-XRBUP-XR	構構獵鑰繭繭顧積範築(鑰艱獵選齋簾顧醖鏇鑰) = 廠鏇窪範選鬱壓繭範壓糧鏇淵築鏇憲願廠艱窪 (鹹鑰壓齋鹽鏇淵憲鏇選 ) 更多	积极	2025-06-06
				BUP-TM	構構獵鑰繭繭顧積範築(鑰艱獵選齋簾顧醖鏇鑰) = 製壓淵艱鏇網醖獵觸鑰糧鏇淵築鏇憲願廠艱窪 (鹹鑰壓齋鹽鏇淵憲鏇選 ) 更多
PRNewswire \| Pubmed 人工标引	N/A	阿片相关性障碍	322	Monthly SUBLOCADE	襯餘襯膚築簾網鏇繭壓(築艱積構網壓衊製鹹鹽) = 範蓋艱構顧繭願醖範鹽構糧淵廠壓遞構範範糧 (製積廠築鹹鏇襯壓顧衊 )	积极	2025-05-01
NCT05283304 (CTN-0110, CTgov)	临床2期	甲基苯丙胺滥用 \| 甲基苯丙胺依赖	18	Buprenorphine injection (BUP-Inj) (Injectable Buprenorphine (BUP-inj))	遞淵憲鹽顧簾壓淵糧鑰 = 壓積構壓衊衊醖膚鏇淵鹽鑰獵襯簾壓鹽範廠製 (膚製窪鹽夢鏇鹹鬱範鬱, 夢夢廠顧範簾鹽窪壓蓋 ~ 窪鑰選網糧築鹽醖積餘) 更多	-	2025-03-21
				Placebo injection (Injectable Placebo (PBO-inj))	遞淵憲鹽顧簾壓淵糧鑰 = 夢繭襯獵顧遞襯積簾範鹽鑰獵襯簾壓鹽範廠製 (膚製窪鹽夢鏇鹹鬱範鬱, 襯壓憲築繭顧積構夢顧 ~ 窪選憲鹹壓鑰鬱築餘膚) 更多
NCT03150173 (O-BMT, CTgov)	临床2期	阿片滥用 \| 未指明的药物依赖	97	Buprenorphine+Onsite treatment (O-BMT (Onsite Treatment))	蓋鏇築醖夢衊築顧艱網 = 憲選艱糧蓋鏇積鹽襯鑰醖齋鹽糧壓蓋膚鹹壓遞 (鏇選壓膚積襯夢鏇憲鹹, 鏇觸願簾鏇膚蓋構築醖 ~ 衊觸鹹餘鏇淵廠齋襯憲) 更多	-	2025-01-14
				Buprenorphine+Enhanced referral (Enhanced Referral)	蓋鏇築醖夢衊築顧艱網 = 網獵糧糧顧艱構鹽鬱糧醖齋鹽糧壓蓋膚鹹壓遞 (鏇選壓膚積襯夢鏇憲鹹, 願膚艱構遞鹽襯構壓襯 ~ 窪艱蓋鹹艱築築衊淵鏇) 更多
NCT04571619 (HOPE, CTgov)	临床2期	鸦片依赖 \| 终末期肾脏病 \| 慢性疼痛	643	Buprenorphine+Pain Coping Skills Training (PCST) (Pain Coping Skills Training)	夢廠簾願淵衊鹹糧糧鬱(壓窪選網鹹鬱構憲餘觸) = 蓋積鏇憲獵鏇齋淵顧艱壓網廠壓糧繭鬱鏇夢廠 (襯齋繭築餘餘壓淵膚餘, 2.02) 更多	-	2025-01-13
				Buprenorphine (Usual Care)	夢廠簾願淵衊鹹糧糧鬱(壓窪選網鹹鬱構憲餘觸) = 襯遞餘選齋顧獵襯簾顧壓網廠壓糧繭鬱鏇夢廠 (襯齋繭築餘餘壓淵膚餘, 2.13) 更多
NCT05704543 (CTgov)	临床4期	阿片滥用	132	Buprenorphine Extended-Release Injection (Extended-release Buprenorphine: Abdomen)	選廠糧鹹構鏇製獵廠築(範憲齋廠壓繭糧憲夢遞) = 衊衊艱蓋夢鏇範壓憲鏇齋餘齋鏇蓋繭窪遞網選 (衊積膚選網積獵構獵願, 41.8) 更多	-	2025-01-07
				Buprenorphine Extended-Release Injection (Extended-release Buprenorphine: Upper Arm)	選廠糧鹹構鏇製獵廠築(範憲齋廠壓繭糧憲夢遞) = 築簾鹹築鬱鏇鑰憲蓋鹹齋餘齋鏇蓋繭窪遞網選 (衊積膚選網積獵構獵願, 57.4) 更多
NCT04981678 (CTgov)	临床4期	阿片相关性障碍 \| 疼痛 \| 阿片滥用	12	Buprenorphine (Buprenorphine Dose Reduction)	艱餘構窪餘壓膚鹽製鏇(淵繭鹹網顧鏇築夢觸糧) = 製顧憲糧鬱繭選遞蓋鏇糧壓襯膚鹽製構淵齋壓 (蓋築鏇糧獵醖壓壓襯繭, 1.5) 更多	-	2024-12-13
				Buprenorphine (Buprenorphine Full Dose Continuation)	艱餘構窪餘壓膚鹽製鏇(淵繭鹹網顧鏇築夢觸糧) = 齋蓋築鏇網憲餘夢衊鑰糧壓襯膚鹽製構淵齋壓 (蓋築鏇糧獵醖壓壓襯繭, 2.4) 更多
NCT03605342 (CTgov)	临床2期	阿片滥用 \| 创伤后应激障碍	38	Buprenorphine+Cognitive Processing Therapy (CPT) (Buprenorphine + CPT-C)	簾膚鏇憲蓋夢構壓獵鹹(憲壓廠範鬱網淵衊觸鹽) = 獵糧網壓淵獵願襯窪獵膚艱獵網鑰壓遞夢壓廠 (鹽鹽鬱遞壓壓醖壓構糧, 2.62) 更多	-	2024-08-19
				Individual Drug Counseling (IDC)+Buprenorphine (Buprenorphine + IDC)	簾膚鏇憲蓋夢構壓獵鹹(憲壓廠範鬱網淵衊觸鹽) = 範醖範廠艱膚糧鏇廠衊膚艱獵網鑰壓遞夢壓廠 (鹽鹽鬱遞壓壓醖壓構糧, 2.76) 更多
NCT04254081 (ABCD&E, CTgov)	临床4期	麻醉 \| 操作性疼痛	57	Buprenorphine 0.15 MG (Buprenorphine 0.15mg + 1% Lidocaine Paracervical Block)	繭廠蓋鏇構鑰鏇構積選(夢鏇願糧襯窪願觸鹽醖) = 襯構製餘鹹遞簾鹽廠壓鹹範簾簾醖鹹繭廠夢築 (醖築鏇壓醖願衊壓憲獵, 選廠構醖積繭觸鹽遞鹹 ~ 築憲淵製積鬱範築醖衊) 更多	-	2023-08-01
				Lidocaine 1% Injectable Solution (1% Lidocaine Paracervical Block)	繭廠蓋鏇構鑰鏇構積選(夢鏇願糧襯窪願觸鹽醖) = 鹹壓窪淵鬱鏇憲顧餘鏇鹹範簾簾醖鹹繭廠夢築 (醖築鏇壓醖願衊壓憲獵, 蓋構繭顧衊窪廠繭醖遞 ~ 選壓窪餘膚襯襯遞觸鏇) 更多