一种基于天然多糖的局部止血剂的最佳组成的论证和研究

V. V. Hladyshev, S. Sоkolovskyi, I. Sobko, Uģis Klētnieks, Audrius Butkevichius
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引用次数: 0

摘要

通过对现有止血方法和产品的分析,医学手段的止血效果明显高于机械方法。然而,重要的是要注意,在大静脉和动脉严重出血的情况下,医疗手段不能完全取代手术止血。在紧急情况下,例如在军事冲突或工作场所受伤期间,最好使用局部接触性止血剂。这些代理不需要专门技能来使用,使需要立即援助的个人可以使用。如果包含在急救箱中,这些药物可以使受害者及时处理轻伤并控制出血。在严重出血的情况下,任何附近的人都可以使用该工具提供援助。鉴于我国境内正在进行的军事活动,研制有效的国产止血剂已成为当务之急。这一举措的目的是确保我们的军事人员能够获得这类产品。这项工作的目的是证明基于现成的原料和可行的技术局部止血剂的最佳组成。材料和方法。在对国内外文献进行了广泛的回顾之后,我们选择了从矿物、合成、植物和有机来源的生物活性成分中提取的吸附材料作为未来接触止血剂发展的基础。本研究的重点是具有潜在止血活性的天然多糖,特别是海藻酸盐、卡帕卡拉胶、瓜尔胶和黄原胶。多糖的一个关键特性是它们的膨胀能力,这对止血有积极的影响。采用机械损伤致股动脉出血模型,评价模型止血成分的止血效果。此外,我们还建立了成年大鼠肝裂伤毛细血管-实质出血模型进行进一步的研究。实验研究证明了天然多糖由于其吸水和肿胀特性而具有止血作用。与知名医疗产品Celox和Revul®相比,具有止血活性的物质,包括海藻酸盐、kappa卡拉胶GU 805和比较药物Celox,已显示出出血时间的显着缩短。具体来说,与阳性对照(PC)组相比,海藻酸盐、kappa卡拉胶GU 805和Celox分别显示出38%、53%和57%的减少。为了提高止血活性,开发了一种主要化合物与添加7%葡萄糖酸钙的组合。在联合用药中加入葡萄糖酸钙与钙离子在凝血各阶段的参与有关,从而增加了联合用药的整体止血效果。结果表明,与PC组相比,海藻酸盐、kappa carragean GU 805联合葡萄糖酸钙、miramistin和植物成分的混合物等具有止血活性的物质以及对照药物Celox和Revul®可可靠地分别缩短出血时间46%、47%、37%和36%。一种接触止血剂的最佳成分,配制成一种多组分粉末,称为Plantor,已经开发出来。该组合物以天然糖为基础,并包含从天然和合成来源获得的防腐剂和伤口愈合物质的复合物。Plantor的配方显示出最佳的一致性、生物制药特性和药物技术特性。在组合物中加入7%的葡萄糖酸钙可以有效地提高止血活性水平。这种增强归因于钙离子参与血液凝固的所有阶段。使用止血模型进行的实验研究证实,所建议的药物治疗剂组合物可显着减少47%的出血时间,并加速整个止血过程。观察到Plantor制剂的疗效优于参考局部止血剂,表明其具有优越的止血效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The justification of the optimal composition and research of a local hemostatic agent based on naturally occurring polysaccharides
The analysis of existing methods and products for controlling bleeding reveals that medical means exhibit significantly higher efficacy compared to mechanical methods of achieving hemostasis. However, it is important to note that medical means cannot entirely replace surgical hemostasis in cases of severe bleeding from large veins and arteries. In emergency situations, such as during military conflicts or workplace injuries, the use of local contact hemostatic agents is preferred. These agents do not require specialized skills for application, making them accessible to individuals in need of immediate assistance. If included in a first-aid kit, these agents enable victims to address minor injuries promptly and control bleeding. In critical bleeding situations, any nearby individual can use the tool to provide aid. Given the ongoing military activities within our country’s territory, the development of effective domestic hemostatic agents has become an urgent priority. This initiative aims to ensure the availability of such products to our military personnel. Aim. The aim of this work is to justify the optimal composition of a local hemostatic agent based on readily available raw materials and feasible technologies. Materials and methods. After conducting an extensive review of domestic and foreign literature, the basis for the development of the future contact hemostatic agent was chosen to be adsorbing materials derived from biologically active components of mineral, synthetic, phyto-, and organic origins. The focus of this study is on natural polysaccharides with potential hemostatic activity, specifically alginate, kappa carrageenan, guar gum, and xanthan gum. One key property of polysaccharides is their ability to swell, which positively influences hemostasis. The hemostatic effect of model hemostatic compositions was evaluated using a femoral artery bleeding model induced by mechanical damage. Additionally, a model involving capillary-parenchymal bleeding from a laceration wound on the liver in adult rats was employed for further investigation. Results. Experimental studies have provided evidence of the hemostatic effect of natural polysaccharides due to their water absorption and swelling properties. In comparison with well-known medical products Celox and Revul®, substances with hemostatic activity, including alginate, kappa carrageenan GU 805, and the comparative drug Celox, have demonstrated significant reductions in bleeding time. Specifically, alginate, kappa carrageenan GU 805, and Celox have shown reductions of 38 %, 53 %, and 57 % respectively, compared to the positive control (PC) group. To enhance the hemostatic activity, a combination of the leading compounds with the addition of 7 % calcium gluconate was developed. The inclusion of calcium gluconate in the combination is associated with the involvement of calcium ions in all stages of blood coagulation, thereby increasing the overall hemostatic effect of the combination. Based on the obtained results, it can be concluded that substances with hemostatic activity, such as alginate, kappa carrageenan GU 805 in combination with calcium gluconate, miramistin, and a mixture of phytocomponents, as well as the comparative drugs Celox and Revul®, reliably reduce bleeding time by 46 %, 47 %, 37 %, and 36 %, respectively, in comparison to the PC group. Conclusions. The optimal composition of a contact hemostatic agent, formulated as a multicomponent powder known as Plantor, has been developed. This composition is based on natural saccharides and incorporates a complex of antiseptic and wound-healing substances derived from natural and synthetic sources. The formulation of Plantor demonstrates optimal consistency, biopharmaceutical properties, and pharmacotechnological characteristics. The addition of 7 % calcium gluconate to the composition was found to effectively enhance the level of hemostatic activity. This enhancement is attributed to the involvement of calcium ions in all stages of blood coagulation. Experimental studies conducted using a hemostatic model have confirmed that the proposed composition of the pharmacotherapeutic agent significantly reduces bleeding time by 47 % and accelerates the overall process of hemostasis. The observed efficacy of the Plantor formulation surpasses that of reference local hemostatic agents, indicating its superior effectiveness in promoting hemostasis.
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