Ripasudil Hydrochloride Hydrate

Akums Drugs & Pharmaceuticals Ltd. has announced the launch of a pioneering Ripasudil-Timolol combination therapy for glaucoma treatment. This Drugs Controller General of India (DCGI)-approved product represents a significant advancement in ophthalmic care, with Akums becoming the first Indian CDMO to receive approval for this innovative formulation. Glaucoma ranks as the second leading cause of irreversible but preventable blindness worldwide, with India contributing to 23.5 percent of the global burden. The condition remains third among causes of vision impairment in India, after cataract and refractive errors. Also, Ocular hypertension is closely linked to glaucoma, many eye care professionals consider ocular hypertension to be a precursor or warning sign for glaucoma. Ocular hypertension refers to elevated pressure within the eye (intraocular pressure or IOP) that is higher than normal but without detectable damage to the optic nerve or visual field loss that would indicate glaucoma. While not everyone with ocular hypertension develops glaucoma, regular monitoring is crucial. Managing both conditions primarily involves lowering intraocular pressure to prevent further complications. The new combination therapy offers a dual mechanism of action for superior intraocular pressure (IOP) control: Ripasudil enhances aqueous humor outflow through the trabecular meshwork, while Timolol reduces aqueous humor production. This synergistic approach delivers more substantial and sustained IOP reduction compared to single-drug treatments. Sanjeev Jain, Managing Director of Akums Drugs & Pharmaceuticals Ltd., said, "This innovation integrates two distinct mechanisms of action to improve glaucoma treatment. By enhancing efficacy and ease of use, we aim to offer a more practical and patient-friendly solution. Our focus is on better clinical outcomes, reducing disease progression, and ultimately improving the quality of life for those affected. With a patient-first approach and a commitment to Make in India, we continue to develop solutions that are of high-quality, and aligned with global standards." The single combination drop formulation significantly simplifies treatment regimens, addressing a major challenge in glaucoma management—patient adherence. By combining two medications into one product, patients benefit from enhanced convenience and potentially improved compliance. "With the rising prevalence of glaucoma in India, introducing therapies that enhance efficacy and patient compliance is crucial," added Sandeep Jain, Managing Director of Akums Drugs & Pharmaceuticals Ltd. "This launch marks a significant step in making high-quality and effective treatment more accessible," added Jain. Akums will utilise its manufacturing facilities to ensure consistent supply and the broad availability of this breakthrough therapy. With approximately 11.9 million people affected by glaucoma in India, this innovative combination addresses a critical healthcare need by providing an effective solution that simplifies treatment while potentially improving outcomes.

该研究发现肝细胞分离导致细胞膜补体抑制分子的降解是诱导肝细胞移植后被机体快速清除的主要原因；发现抑制ROCK可维持肝细胞膜蛋白的完整性、阻断膜攻击复合体的组装、并显著提高肝细胞移植后的定植效率（图3） 肝细胞移植作为原位肝移植的一种潜在的替代疗法，对于终末期肝病的治疗具有重要的研究意义，其优点包括：手术创伤小、操作简单、可进行多次移植等。然而，仍有一些障碍阻碍了肝细胞移植的临床应用。例如，大多数临床研究中使用的肝细胞通常来源于不适合器官移植的肝脏，肝细胞的来源和质量严重限制了肝细胞移植的应用。 近年来，由多能干细胞分化或者通过谱系重编程来得到的肝细胞或肝祖细胞的研究取得了显著的进步，有望最终解决此问题。肝细胞移植的另一个主要限制是肝细胞的体内植入效率极低。在肝细胞移植后的24小时内超过70％的肝细胞因血液介导的即刻炎症反应（Instant blood-mediated inflammatory reaction，IBMIR）而被清除；存活的肝细胞还必须穿过肝窦内皮细胞屏障迁移至肝板，并与宿主肝细胞建立细胞连接后才能成功植入宿主肝脏，最终只有大约2%-6%的肝细胞可以成功定植到宿主肝脏。 因此，提高肝细胞移植后在肝脏中的定植效率，是肝细胞移植应用于临床的迫切需要解决的问题。 近日，海军军医大学李文林团队在 Molecular Therapy 期刊发表了题为：ROCK inhibition enhanced hepatocyte liver engraftment by retaining membrane CD59 and attenuating complement activation 的研究论文。 该研究表明，肝细胞的分离导致细胞膜蛋白（包括补体抑制分子CD59）的大量降解，ROCK（Rho-associated coiled-coil containing kinases）抑制剂可以通过保留细胞膜CD59和阻断膜攻击复合物（membrane attack complex，MAC）的形成来保护移植的肝细胞、提高肝细胞的定植效率。 在这项研究中，研究团队通过筛选发现ROCK抑制剂可显著增强肝细胞移植后在肝脏中的定植。体外补体活化实验表明ROCK抑制剂可以阻断膜攻击复合体（C5b-9）在肝细胞表面的组装（图1）。体内实验进一步证实了抑制ROCK可保护移植的肝细胞免受宿主补体系统的攻击。