The justification of the optimal composition and research of a local hemostatic agent based on naturally occurring polysaccharides

Authors

DOI:

https://doi.org/10.14739/2409-2932.2023.2.281238

Keywords:

pharmaceutical products, polysaccharides, hemostatic, calcium gluconate, plant extracts, essential oils

Abstract

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.

Author Biographies

V. V. Hladyshev, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, DSc, Professor, Head of the Department of Medicinal Preparations Technology

S. І. Sоkolovskyi, Limited Liability Company “European Medical University”, Dnipro, Ukraine

MD, PhD, Associate Professor, Vice-Rector for International Relations

I. V. Sobko, Military medical academy of Ukraine, Kyiv

MD, PhD, Colonel of the Medical Service, Associate Professor of the Department of Military Surgery

Ugіs Kletnieks, Latvian Longevity Association, Jurmala

Doctor of MBA, Member of the Board of the Smart Materials and Technologies Competence Center

Audrius Butkevichius, International Nobel Information Centre, Official Representation in Ukraine, Dnipro

MD, Moderator of Projects on Military Medicine

References

Malik, A., Rehman, F. U., Shah, K. U., Naz, S. S., & Qaisar, S. (2021). Hemostatic strategies for uncontrolled bleeding: A comprehensive update. Journal of biomedical materials research. Part B, Applied biomaterials, 109(10), 1465-1477. https://doi.org/10.1002/jbm.b.34806

Schauer, S. G., Naylor, J. F., Oliver, J. J., Maddry, J. K., & April, M. D. (2019). An analysis of casualties presenting to military emergency departments in Iraq and Afghanistan. The American journal of emergency medicine, 37(1), 94-99. https://doi.org/10.1016/j.ajem.2018.04.068

Rass, V., & Helbok, R. (2021). How to diagnose delayed cerebral ischaemia and symptomatic vasospasm and prevent cerebral infarction in patients with subarachnoid haemorrhage. Current opinion in critical care, 27(2), 103-114. https://doi.org/10.1097/MCC.0000000000000798

Teixeira, P. G. R., Brown, C. V. R., Emigh, B., Long, M., Foreman, M., Eastridge, B., Gale, S., Truitt, M. S., Dissanaike, S., Duane, T., Holcomb, J., Eastman, A., Regner, J., & Texas Tourniquet Study Group (2018). Civilian Prehospital Tourniquet Use Is Associated with Improved Survival in Patients with Peripheral Vascular Injury. Journal of the American College of Surgeons, 226(5), 769-776.e1. https://doi.org/10.1016/j.jamcollsurg.2018.01.047

Palmer, L. (2022). Hemorrhage control-Proper application of direct pressure, pressure dressings, and tourniquets for controlling acute life-threatening hemorrhage. Journal of veterinary emergency and critical care, 32(S1), 32-47. https://doi.org/10.1111/vec.13116

Sung, Y. K., Lee, D. R., & Chung, D. J. (2021). Advances in the development of hemostatic biomaterials for medical application. Biomaterials research, 25(1), 37. https://doi.org/10.1186/s40824-021-00239-1

Lee, C., Rasmussen, T. E., Pape, H.-C., Gary, J. L., Stannard, J. P., & Haller, J. M. (2021). The polytrauma patient: Current concepts and evolving care. OTA International: The Open Access Journal of Orthopaedic Trauma, 4(2S), e108. https://doi.org/10.1097/oi9.0000000000000108

Wang, X. X., Liu, Q., Sui, J. X., Ramakrishna, S., Yu, M., Zhou, Y., Jiang, X. Y., & Long, Y. Z. (2019). Recent Advances in Hemostasis at the Nanoscale. Advanced healthcare materials, 8(23), e1900823. https://doi.org/10.1002/adhm.201900823

Thompson, P., & Strandenes, G. (2019). The History of Fluid Resuscitation for Bleeding. In Damage Control Resuscitation: Identification and Treatment of Life-Threatening Hemorrhage (pp. 3-29). Springer International Publishing. https://doi.org/10.1007/978-3-030-20820-2_1

Mazuchowski, E. L., Kotwal, R. S., Janak, J. C., Howard, J. T., Harcke, H. T., Montgomery, H. R., Butler, F. K., Holcomb, J. B., Eastridge, B. J., Gurney, J. M., & Shackelford, S. A. (2020). Mortality review of US Special Operations Command battle-injured fatalities. The journal of trauma and acute care surgery, 88(5), 686-695. https://doi.org/10.1097/TA.0000000000002610

Kotwal, R. S., Scott, L. L. F., Janak, J. C., Tarpey, B. W., Howard, J. T., Mazuchowski, E. L., Butler, F. K., Shackelford, S. A., Gurney, J. M., & Stockinger, Z. T. (2018). The effect of prehospital transport time, injury severity, and blood transfusion on survival of US military casualties in Iraq. The journal of trauma and acute care surgery, 85(1S Suppl 2), S112-S121. https://doi.org/10.1097/TA.0000000000001798

Howard, J. T., Kotwal, R. S., Stern, C. A., Janak, J. C., Mazuchowski, E. L., Butler, F. K., Stockinger, Z. T., Holcomb, B. R., Bono, R. C., & Smith, D. J. (2019). Use of Combat Casualty Care Data to Assess the US Military Trauma System During the Afghanistan and Iraq Conflicts, 2001-2017. JAMA surgery, 154(7), 600-608. https://doi.org/10.1001/jamasurg.2019.0151

Huang, L., Liu, G. L., Kaye, A. D., & Liu, H. (2020). Advances in Topical Hemostatic Agent Therapies: A Comprehensive Update. Advances in therapy, 37(10), 4132-4148. https://doi.org/10.1007/s12325-020-01467-y

Hu, Z., Zhang, D. Y., Lu, S. T., Li, P. W., & Li, S. D. (2018). Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Marine drugs, 16(8), 273. https://doi.org/10.3390/md16080273

Li, X. F., Lu, P., Jia, H. R., Li, G., Zhu, B., Wang, X., & Wu, F. G. (2023). Emerging materials for hemostasis. Coordination Chemistry Reviews, 475, 214823. https://doi.org/10.1016/j.ccr.2022.214823

Hatamabadi, H. R., Asayesh Zarchi, F., Kariman, H., Arhami Dolatabadi, A., Tabatabaey, A., & Amini, A. (2015). Celox-coated gauze for the treatment of civilian penetrating trauma: a randomized clinical trial. Trauma monthly, 20(1), e23862. https://doi.org/10.5812/traumamon.23862

Grubnik, I. M., Nikolaychuk, N. O., & Gladukh, Ye. V. (2010). Vplyv tekhnolohichnykh parametriv na reolohichni vlastyvosti vodnykh rozchyniv hidrokoloidiv [The influence of technological parameters on rheological properties of water solutions of hydrocolloids]. Visnyk farmatsii, (4), 30-32. [in Ukrainian].

Osmanov, A., Farooq, Z., Richardson, M. D., & Denning, D. W. (2020). The antiseptic Miramistin: a review of its comparative in vitro and clinical activity. FEMS microbiology reviews, 44(4), 399-417. https://doi.org/10.1093/femsre/fuaa012

Published

2023-07-03

How to Cite

1.
Hladyshev VV, Sоkolovskyi SІ, Sobko IV, Kletnieks U, Butkevichius A. The justification of the optimal composition and research of a local hemostatic agent based on naturally occurring polysaccharides. Current issues in pharmacy and medicine: science and practice [Internet]. 2023Jul.3 [cited 2024May24];16(2):141-6. Available from: http://pharmed.zsmu.edu.ua/article/view/281238

Issue

Section

Original research