INTERFERON ALFA-2B(Merck Sharp & Dohme )

在注射剂研发与生产中，药物溶解性与稳定性是两大核心难题。交联聚维酮（PVPP）作为一种新型药用辅料，凭借独特的分子结构与理化性质，在提升注射剂稳定性、增溶难溶性药物方面展现出显著优势。本文将从PVPP的作用机制、应用场景及实际价值三个维度，解析其如何为注射剂研发提供有效解决方案。 一、PVPP的结构特性与作用原理 交联聚维酮（PVPP）是通过交联反应形成的不溶性聚维酮衍生物，具有三维网状结构和大量内部分子孔道。这种结构使其兼具良好的吸附能力与空间稳定性： 吸附作用：PVPP分子中的N-乙烯基吡咯烷酮单元可通过氢键、范德华力与药物分子形成可逆结合，有效增加药物在溶剂中的分散性增溶机制：内部分子孔道可包裹疏水药物分子，形成纳米级分散体系，提升药物溶解度（据《中国医药工业杂志》2023年数据，PVPP可使难溶性药物溶解度提升3-5倍）稳定效果：通过抑制药物分子聚集与氧化反应，延长制剂有效期，减少降解产物生成 二、注射剂研发中的关键应用场景 在实际生产中，PVPP已在多个注射剂领域实现突破性应用： 1. 抗生素类注射剂 针对青霉素类、头孢类等易水解抗生素，PVPP可通过吸附降解中间体（如β-内酰胺环水解产物），将药物降解速率降低40%以上。某跨国药企临床数据显示，使用PVPP稳定的头孢哌酮钠制剂，48小时降解率从18%降至7%。 2. 抗肿瘤注射剂 紫杉醇、阿霉素等疏水性抗肿瘤药物，常因溶解度低导致临床应用受限。PVPP可与药物形成1:3~1:5的包合复合物，在生理盐水体系中实现药物浓度提升至10mg/mL以上，且保持溶液物理稳定性长达12个月。 3. 生物制剂稳定化 在重组蛋白类注射剂中，PVPP通过吸附体系中游离金属离子（如Fe³⁺、Cu²⁺），阻断Fenton反应链，减少蛋白质氧化失活。某生物技术公司采用PVPP后，重组人干扰素α-2b注射液的货架期延长至24个月（原12个月）。 三、巨和化工PVPP的技术优势 作为行业领先的药用辅料供应商，巨和化工的交联聚维酮产品具有显著技术特点： 高纯度：采用食品级原料制备，重金属残留＜1ppm，符合USP/EP注射级标准低溶出：严格控制灰分含量（＜0.1%），避免微粒污染风险批间一致性：通过动态交联工艺，实现粒径分布（D50）稳定在150-200μm范围成本优化：相比传统增溶剂（如泊洛沙姆、环糊精），PVPP可降低单位药物增溶成本15-20% 四、应用案例与市场反馈 某创新药企研发的新型抗抑郁注射剂中，因原辅料配伍问题导致药物稳定性不足。引入巨和化工PVPP后： 药物初始溶解度从0.8mg/mL提升至3.2mg/mL4℃储存条件下，6个月内降解率控制在5%以内临床前动物实验显示，药物生物利用度提升28% 该案例已被《中国药学杂志》收录为"新型药用辅料应用典型案例"。 随着医药行业对注射剂质量要求的提升，交联聚维酮（PVPP）正成为解决药物增溶与稳定的关键技术手段。巨和化工凭借多年研发经验，已构建从实验室筛选到工业化生产的完整解决方案，为药企提供从药物发现到商业化生产的全链条技术支持。选择PVPP作为注射剂辅料，不仅能提升产品质量，更能降低研发周期与生产成本，实现医药创新价值最大化。

Re-induction with ADSTILADRIN resulted in complete responses in 31% of initial non-responders with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (n=13) Findings suggest re-induction may allow additional patients to achieve a complete response in a real‑world setting Results presented at the 2026 American Urological Association (AUA) Annual Meeting and scheduled for publication in Translational Andrology and Urology in May 2026 PARSIPPANY, N.J.--(BUSINESS WIRE)--Ferring Pharmaceuticals today announced a new real-world case series demonstrating that re-induction with ADSTILADRIN ® (nadofaragene firadenovec-vncg) resulted in complete responses (CR) in approximately 31% (4/13) of patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) who did not respond to an initial dose of therapy. The study included patients with carcinoma in situ (CIS), with or without papillary tumors (±Ta/T1). The findings – presented at the 2026 American Urological Association (AUA) Annual Meeting and scheduled for publication in Translational Andrology and Urology later in May – reflect outcomes observed following a re-induction dose (second dose overall) of ADSTILADRIN in a real-world clinical setting, including two patients (2/13) with CIS with papillary disease (T1). 1 ADSTILADRIN is the first and only non-replicating intravesical gene therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with high-risk BCG-unresponsive NMIBC with CIS, with or without papillary tumors (±Ta/T1), and is administered once every three months. “These findings offer a promising signal that some patients who do not achieve a complete response after an initial dose of ADSTILADRIN may still benefit from re-induction,” said Chad Reichard, MD, urologic oncologist and Director of Oncology at Urology of Indiana. “Real-world evidence provides important insight into how ADSTILADRIN is being used in routine clinical practice, and the responses observed in this study support the feasibility of re-induction as a potential option for certain patients despite an initial non-response, while highlighting the need for further study.” The retrospective, observational cohort study analyzed electronic health record data from U.S. private urology practices. Thirteen patients with BCG‑unresponsive NMIBC were eligible, including eight with CIS alone, two with CIS and papillary disease (Ta), and three with CIS and papillary disease (T1). Patients had a mean age of 77.5 years; all were male and had received a mean of 11 prior BCG doses. Prior treatments included gemcitabine (n=4) and pembrolizumab (n=5). Median follow‑up following re‑induction was 379 days (range, 135–519). After re‑induction, four patients (30.8%) achieved a complete response, including two patients with CIS and T1 disease. Among patients who achieved a complete response, three went on to receive additional doses of ADSTILADRIN; one patient has maintained a complete response at last follow‑up. One patient experienced progression to muscle‑invasive disease (T2a), and one patient underwent cystectomy approximately 51 weeks after initiation of therapy. At the time of analysis, no patient deaths had been reported. “These new data add to the growing body of real-world evidence generated in urology practices and help inform how re-induction with ADSTILADRIN is being evaluated outside of the controlled clinical trial setting, particularly in a heavily pretreated patient population,” said Daniel Shoskes, MD, MSc, FRCS(C), Vice President, Global Medical Director Uro-Oncology, Ferring Pharmaceuticals. “In the Phase 2 and Phase 3 clinical trials, patients who did not achieve a complete response at three months were not retreated with ADSTILADRIN. However, re-induction is an approach that has been used with some immune-based therapies. These real‑world findings provide insight into how re-induction may improve complete response outcomes over the course of treatment.” About Non-Muscle Invasive Bladder Cancer (NMIBC) NMIBC is a form of bladder cancer that is found in the inner layer cells of the bladder and does not invade into or beyond the muscle wall. 2 In the United States, bladder cancer is the sixth most common cancer, 3 fourth among men, 4 and it is estimated that there will be approximately 84,870 new cases of bladder cancer in the U.S. in 2025. 4 Historically, 75% of bladder cancer presents as NMIBC. 5 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard-of-care; however, approximately one third of patients with NMIBC will not respond to BCG therapy and 50% of those with an initial response will experience recurrence or progression of their disease. 6 Current treatment options for BCG-unresponsive patients are very limited and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder). 7 About ADSTILADRIN ADSTILADRIN ® (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical non-replicating gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1). It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered locally as a monotherapy by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high and transient local expression of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer. ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-risk, BCG-unresponsive NMIBC, who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849 and final five-year follow-up analysis published in The Journal of Urology ). 8-9 INDICATION ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product. WARNINGS AND PRECAUTIONS: Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy. Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals. DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use or oral administration. USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose. ADVERSE REACTIONS: The most common (>10%) adverse reactions; including, laboratory abnormalities (>15%), were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition (urination urgency), increased creatinine, hematuria (blood in urine), decreased phosphate, chills, pyrexia (fever) and dysuria (painful urination). You are encouraged to report negative side effects of prescription drugs to FDA. Visit or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING. Please click to see the full Prescribing Information . About Ferring Pharmaceuticals Ferring Pharmaceuticals is a privately-owned, specialty, biopharmaceutical group committed to building families and helping people live better lives. In the United States, Ferring is a leader in reproductive medicine and in areas of gastroenterology and orthopaedics. We are at the forefront of innovation in microbiome-based therapeutics and uro-oncology intravesical gene therapy. Our company was founded in 1950 and is headquartered in Saint-Prex, Switzerland. Ferring employs more than 7,000 people worldwide and markets its medicines in over 100 countries. Ferring USA is based in Parsippany, New Jersey, and employs more than 900 employees. For more information, please visit , call 1-888-FERRING (1-888-337-7464), or connect with us on LinkedIn , and X . References: Reichard C, Trainer A, Grant K, et al. A Real‑World Case Series Of Re‑Induction With Nadofaragene Firadenovec In Patients With Carcinoma In Situ ± Papillary Non–Muscle‑Invasive Bladder Cancer. 121st Annual Meeting of the American Urological Association, Washington, DC, United States. Urology Care Foundation. Non-muscle Invasive Bladder Cancer. . Accessed April 2026. National Cancer Institute. Cancer Statistics. . Accessed April 2026. American Cancer Society. Cancer Facts & Figures 2025. . Accessed April 2026. Babjuk M, Burger M, Capoun O, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer. Eur Urol. 2022 Jan;81(1):75-94. . Accessed April 2026. Lidagoster S, et al. BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer. Curr Oncol. 2024 Feb 16;31(2):1063-1078. . Accessed April 2026. National Comprehensive Cancer Network. Bladder Cancer (Version 1.2026). . Accessed April 2026. ADSTILADRIN in Patients With High-Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Gov Identifier: NCT02773849. . Accessed April 2026. Narayan VM, Boorjian SA, Alemozaffar M, et al. Efficacy of intravesical nadofaragene firadenovec for patients with Bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer: 5-year follow-up from a phase 3 trial. J Urol.2024;212(1):1-12. . Accessed April 2026. Contacts For more information, please contact: Carol Ready Director, Brand Communications (973) 765-7307 carol.ready@ferring.com