Antihemorrhagic Agents Research Articles

The marketing study of the pharmaceutical market of Ukraine in the segment of antihemorrhagic agents to stop dental bleeding

Aim. To conduct the marketing research of the Ukrainian market in the segment of antihemorrhagic agents used in dentistry.Materials and methods. The study was performed using the structural analysis, logical and graphical methods, marketing analysis methods.Results. The state of the Ukrainian market of drugs of this group has been determined. The market structure has been revealed in the number of names, brands, in forms of production, manufacturers, composition. Despite the sufficient number of registered drugs at the market (26 positions), a rather small arsenal of active substances (4) and dosage forms (3) can be observed. The market is characterized by a limited amount of drugs with a certain pharmacodynamics combining a rapid hemostatic effect, safety in use, the ability to suppress bacterial flora, and without the effect on healthy tissues. However, a positive moment should be noted: by the structure of manufacturer countries the market remains domestic (60 : 40).Conclusions. The Ukrainian pharmaceutical market is characterized by a sufficient assortment of hemostatic agents, but the use of these drugs in dentistry has its limitations. Dental doctors have certain problems with the occurrence of capillary bleeding and require a sufficient amount of effective and fastacting drugs for local application. Therefore, the search and creation of new drugs with a similar action at this stage remains a relevant scientific issue.

A Case Report of Intraoperative Coagulopathy Secondary to Chronic Vitamin K Deficiency.

Dietary Vitamin K is a well-known anti-hemorrhagic agent that plays an integral role in the coagulation pathway. Vitamin K is involved in synthesis of coagulation factors; II, VII, IX and factor X. Vitamin K deficiency leads to bleeding diathesis. Hemorrhages usually present in deep soft tissue, rather than mucosal or epithelial membranes, bleeding that is generally caused by disorders of platelets. Major causes of vitamin K deficiency include; medications and diseases involving fat metabolism with a resultant fat malabsorption. Warfarin and Cephalosporins are one of the commonly prescribed medications that lead to vitamin K deficiency. Disease affecting fat metabolism pathway, such as; diseases of the pancreas (cystic fibrosis), short gut syndrome and certain pathologies of the biliary tree. Vitamin K deficiency is more common in newborns. In adults it is uncommon because of its ubiquitous nature and the abundance of its sources. Hemorrhagic disorders in adults due to Vitamin K deficiency are not commonly encountered in practice. We are presenting a case of an adult who presented with a compartment syndrome secondary to a traumatic intramuscular bleeding. Our case highlights the importance of considering vitamin K deficiency in the differential diagnosis of unexplained hemorrhages resulting from a coagulopathy.

Analysis of sales volumes of herbal remedies with hemostatic effect

The aim of the study. Determination of sales volumes of drugs with hemostatic action and analysis of sales features of plant hemostatic drugs.Materials and methods. The market research and sales volumes of hemostatic drugs were carried out using the content analysis of the State Register of medicines and according to the analytical system of research of the pharmaceutical market Pharm-Xplorer/Pharm standard of Proxima Research Company.Results. The assortment of registered hemostatic drugs on the Ukrainian market and the availability of these drugs according to sales data in the retail segment were analyzed. The presence of hemostatic drugs of the plant origin in the market of foreign countries has been analyzed. The dynamics of sales of hemostatic medicines and in particular of herbal drugs in natural and monetary equivalents in the pharmaceutical market of Ukraine was researched. The segments of medicine in which hemostatic drugs are prescribed were analyzed. The volume of sales of herbal means of hemostatic action compared with other hemostatic drugs in some medical segments was investigated.Conclusions. Available 76.5 % of medicine are from the assortment of registered hemostatic drugs. There are no preparations of plant origin with hemostatic action of foreign manufacturers in the Ukrainian market. The leader in sales in monetary terms is tranexamic acid – 33%. Hemostatic agents of plant origin are in a small and low-grade group of drugs. Antihemorrhagic agents of plant origin are most often prescribed in gynecology and are most commonly sold through non-prescription pharmacy sales.

Evaluated bioactive component extracted from Punica granatum peel and its Ag NPs forms as mouthwash against dental plaque

Abstract The bioactive components of the hydroalcoholic (MeOH 70%) Punica granatum peel crude extract (PGPC) and its methanol fraction (PGPM) were extracted and tentatively identified by LCMS/MS as a number of phenolic compounds which are used as capping agents fasting the reduction of Ag+ to Ag (0). The prepared silver nano-particles Ag NPs PGPC and Ag NPs PGPM were characterized by the transmission electron microscopy (TEM) and UV–vis spectra. Four mouthwashes were designed using PGPC, PGPM, Ag NPs PGPC and Ag NPs PGPM. The prepared mouthwashes exhibited a significant antimicrobial activity against the Streptococcus mutans and the three dental plaque isolates called Lysinibacillus cresolivorans, Lysinibacillus cresolivorans and Lysinibacillus boronitolerans. As well as, the prepared Ag NPs mouthwashes led to reduction in the cytotoxicity against BJ-1 cell line equal 35 and 23.66% with LC50 = 185.16 and 134.8 μg/mL. Finally, phenolics promote Ag NPs PGPM mouthwash to be potent anti-calculus and anti-hemorrhagic agents.

Investigation of the Differences of Immunological Characteristics of Mecsina Hemostopper®, Ankaferd Blood Stopper® and Tranexamic Acid Used as Haemostatic Agents with Cell Culture Study

Objective: Hemorrhagic complications may develop in many branches of medicine and dentistry after or during the treatment independently of the extent of the procedure performed. Various biomaterials have been used in the medical and dental practice procedures before and after surgical procedures. The aim of this study was to compare the immunological efficacies and effects of Ankaferd Blood Stopper, Tranexamic acid used as anti-hemorrhagic agents and Mecsina Blood Stopper, a new anti-hemorrhagic agent.Method: The immortalized HUVEC (Human Umbilical Vein Endothelial Cell) cell lines, which are human umbilical cord cells and used in many studies on coagulation and formation of fibrin, were commercially purchased for the study. The cells, 5000 cells per flask for each drug, were distributed into the 5 groups (ankaferd, Tranexamic acid, mecsina, distilled water-administered negative and control without any administration). Results: According to the data we obtained, TNF alpha (Tumor Necrosis Factor Alpha) levels were found to be lower in the cells, to which mecsina was administered at concentrations of 1: 2 and 1:10, than other drug groups (p<0,05). There was a significant increase in IL-1B (Interleukin 1B) and IL6 (Interleukin 6) levels in all drug administrations at both concentrations of 1: 2 and 1: 10 compared to the control group (p <0,05). While there was no significant increase in TNF alpha levels in all drug administrations at a concentration of 1: 2 (p <0,05), there was no significant correlation in mecsina administration at a concentration of 1:10 (p> 0,05), but a significant increase was found in tranexamic acid (TA) and ankaferd administrations (p <0.05). Conclusion: In conclusion, it has been observed that different anti-hemorrhagic agents administered at different concentrations in HUVEC cell groups produced a significant increase in intracellular cytokine levels. Considering the results, we can say that MH (Mecsina Hemostopper) administration is a more effective anti-hemorrhagic agent than administrations of ABS (Ankaferd Blood Stoper) and especially TA (Tranexamic Acid).

Phenotypic Screening To Discover Novel Chemical Series as Efficient Antihemorrhagic Agents.

In an effort to find novel chemical series as antifibrinolytic agents, we explore α-phenylsulfonyl-α-spiropiperidines bearing different zinc-binding groups (ZBGs) to target those metalloproteinases involved in the fibrinolytic process: MMP3 and MMP10. Surprisingly, all these new chemical series were inactive against these metalloproteinases; however, several new molecules retained the antifibrinolytic activity in a phenotypic functional assay using thromboelastometry and human whole blood. Further optimization led to compound 38 as a potent antifibrinolytic agent in vivo, three times more efficacious than the current standard-of-care (tranexamic acid, TXA) at 300 times lower dose. Finally, in order to decipher the underlying mode-of-action leading to this phenotypic response, an affinity-based probe 39 was successfully designed to identify the target involved in this response: a potentially unknown mechanism-of-action in the fibrinolytic process.

Dry-field maneuver for controlling the massive intraventricular bleeding during neuroendoscopic procedures.

Massive hemorrhages pose a significant problem in intraventricular endoscopic surgeries. These hemorrhages have the potential to cause mortality and morbidity, particularly in excisional surgeries. Often, the bleeding can be controlled only by cauterization and liquid irrigation, due to the incongruity of the use of antihemorrhagic agents in the fluid. The final option to stop the massive bleeding is the dry-field maneuver. In this study, the effects and clinical results of the dry-field maneuver in bleeding control of a massive bleeding were investigated. Dry-field maneuver was retrospectively studied in a patient population that had massive bleeding during intraventricular endoscopic procedures. Dry-field maneuver was used in seven patients. Four of these patients underwent some excisional surgery. The other two patients were operated for an endoscopic third ventriculostomy and one for intraventricular hemorrhage evacuation. It was observed that the hemorrhage in patients stopped rapidly after the dry-field maneuver. Moreover, there was no need for an antihemorrhagic material. Dry-field maneuver is an option for providing hemostasis, particularly, for a massive hemorrhage. It also has the potential to be used in elective surgeries because it improves the visual quality.

Bleeding after tonsillectomy

Oropharyngeal hemorrhage after tonsillectomy is one of the most common postprocedural ENT emergencies that require immediate attention. Management choices depend on the severity of bleeding, underlying platelet or coagulation disorders, and the patient’s maturity and age. Treatment range from simple observation to an emergent need to both secure the airway and stop the hemorrhage. The workup of the hemorrhagic patient will be discussed from the preoperative to postoperative time period. Surgical techniques in response to various acuity will be discussed to fully elucidate options to control the hemorrhage.

Amelioration of acute myocardial infarction by saponins from flower buds of Panax notoginseng via pro-angiogenesis and anti-apoptosis

Ethnopharmacological relevanceThe root of Panax notoginseng is traditionally used as an anti-hemorrhagic agent to promote blood circulation without causing “congealed” blood. Furthermore, the flower of P. notoginseng is a popular, traditional medicine taken daily for the preventing of hypertension and for reducing blood cholesterol profiles. Besides, the flower of P. notoginseng contains a higher level of saponins, particularly protopanaxadiol-type ginsenosides, as compared to the root. However, detailed pharmacological studies on this flower have rarely been conducted. Material and methodsIn this study, the saponins extracted from the flower of P. notoginseng (FS) were examined on the endothelial cell migration assay, chemically induced vascular insufficiency model in zebrafish larvae and myocardial infraction (MI) model in rats, for determination of their pro-angiogenic and therapeutic effects on MI treatment. ResultsOur results demonstrate that FS significantly promoted VEGF-induced migration of human umbilical vein endothelial cells (HUVECs) and partially restored defective intersegmental vessels (ISV) in a chemically induced vascular insufficiency model of zebrafish larvae. When compared to MI group, two weeks post-treatment of FS (25–50mg/kg/day) induced approximately 3-fold upregulation of VEGF mRNA expression and a concomitant increase in blood vessel density in the peri-infarct area of the heart. Moreover, TUNEL analysis indicates a reduction in the mean apoptotic nuclei per field in peri-infarct myocardium upon FS treatment. ConclusionsThe pro-angiogenic effects of FS demonstrated in in vitro and in vivo experimental models suggest that the purified saponin preparation from flowers of P. notoginseng may potentially provide preventive and therapeutic agent for cardiovascular diseases.

Discovery and safety profiling of a potent preclinical candidate, (4-[4-[[(3R)-3-(hydroxycarbamoyl)-8-azaspiro[4.5]decan-3-yl]sulfonyl]phenoxy]-N-methylbenzamide) (CM-352), for the prevention and treatment of hemorrhage.

Discovery of potent and safe therapeutics that improve upon currently available antifibrinolytics, e.g., tranexamic acid (TXA, 1) and aprotinin, has been challenging. Matrix metalloproteinases (MMPs) participate in thrombus dissolution. Then we designed a novel series of optimized MMP inhibitors that went through phenotypic screening consisting of thromboelastometry and mouse tail bleeding. Our optimized lead compound, CM-352 (2), inhibited fibrinolysis in human whole blood functional assays and was more effective than the current standard of care, 1, in the tail-bleeding model using a 30 000 times lower dose. Moreover, 2 reduced blood loss during liver hepatectomy, while 1 and aprotinin had no effect. Molecule 2 displayed optimal pharmacokinetic and safety profiles with no evidence of thrombosis or coagulation impairment. This novel mechanism of action, targeting MMP, defines a new class of antihemorrhagic agents without interfering with normal hemostatic function. Furthermore, 2 represents a preclinical candidate for the acute treatment of bleeding.

Ellagic acid encapsulated chitosan nanoparticles as anti-hemorrhagic agent

Ellagic acid, a naturally occurring polyphenol was encapsulated in chitosan particles prepared by ionotropic gelation and characterized for its physicochemical properties. A maximum encapsulation efficiency of 49% was achieved. The blood clotting time and clot retraction time were calculated for different concentrations of ellagic acid, chitosan and ellagic acid-encapsulated chitosan. A reduction of 34% in the clot time and 16.4% in the retraction time was observed in ellagic acid-encapsulated chitosan when compared with free ellagic acid at concentrations as low as 0.1mg/mL. The physical blend in comparison to free ellagic acid displayed a reduction of 13.8% and 4.6% in the clotting time and retraction time respectively under similar conditions. This suggests that the encapsulation of ellagic acid favors thrombosis due to synergistic action of chitosan and ellagic acid on same molecular targets. This study demonstrates the potential of ellagic acid–chitosan system as an effective anti-hemorrhagic system.

Anti-Hemorrhagic Agents in Oral and Dental Practice: An Update

Many oral surgeons in their daily practice have the problem of controlling postoperative bleeding. In surgical, oral and maxillofacial practice, standard anti-hemorrhagic protocols, especially in high risk patients, are obviously required and need to be continuously updated. The purpose of this review is to give a rational insight into the management of bleeding in oral and dental practice through modern drugs and medical devices such as lysine analogues and serine protease inhibitors, desmopressin, fibrin sealants, cyanoacrylates, gelatins, collagen and foams, protein concentrates, recombinant factors, complementary and alternative medicine and other compounds.

A case of diffuse alveolar hemorrhage after tonsillectomy -A case report-

Diffuse alveolar hemorrhage (DAH) is an acute, life-threatening event. The blood-gas barrier must be very thin to allow gas exchange and is therefore subjected to high mechanical stresses when the capillary pressure rises. In general anesthesia, inhaled gases cause high mechanical stresses, and thus DAH occurs under certain conditions. We describe a case of inferred postoperative DAH. A 25-year-old man had an acute episode after undergoing a tonsillectomy for snoring. During surgery, no problems occurred and no marked bleeding was observed. After removal of the endotracheal tube, however, the patient had severe cough and hemoptysis. The patient was treated with an antihemorrhagic agent and antibiotics. He recovered after 1 week. Chronic snoring likely caused the alveolar damage in this patient and intubation led to DAH. The patient presented with a benign course that regressed spontaneously with medical intervention.

Successful Management of Bleeding after Dental Procedures with Application of Blood Stopper: A Single Center Prospective Trial

Ankaferd Blood Stopper (ABS), as an herbal complementary medicine, has been approved for the management of clinical hemorrhages in Turkey, including dental interventions. Basic, preclinical and clinical studies disclosed the settings of the topical hemostatic use of ABS. The aim of this study is therefore to assess the efficacy and safety of ABS as an antihemorrhagic agent in the bleedings associated with dental procedures in patients with normal and impaired hemostasis. ABS has been topically applied by homogeneously spraying to the 113 patients during dental interventions within its on-label indications. A median of 0.5 ml (IQR:0.5-1 ml) ABS was administered after tooth extraction with prolonged hemorrhages. After the administration, bleeding stopped in less than 10 seconds in 59 (52.2%) patients, and below 22.5 seconds (IQR: 18, 8-30) in 54 patients (47.8%). A total of 141 procedures were performed in these 113 patients, and nearly 72.5 ml ABS was used with a total cost of 98 €. ABS as a new herbal medicine was found to be an effective method for controlling bleeding related to dental procedures. No patient had wound infection and the healing process appeared to be normal. Topical ABS could be useful for the local hemostasis and wound healing in periodontal surgeries. In this prospective study ABS, for the first time, has demonstrated its potential for being an effective hemostatic agent for the management of bleedings due to dental procedures.

괴화((槐花), Flos Sophora japonica Linne) 추출물의 생리활성

괴화추출물은 DPPH free radical 소거법에 의한 항산화활성 실험에서는 ethyl acetate 분획(RC??＝3.13 ㎍/mL), butanol 분획(RC??＝6.25 ㎍/mL)에서 강한 항산화 활성을 보였으며, α-tocopherol이나 BHA보다 유사하거나 강한 항산화 활성을 나타냈다. Linoleic acid에 대한 항지질과산화활성 실험은 15일째에 물층을 제외한 추출물, 분획물에서 높은 활성을 나타내었다. 박테리아에 대한 항균실험은 Staphylococcus aureus에서만 활성을 보이지 않았을 뿐 다른 피검균에서는 높은 활성을 보였다. 다만, fungi strain인 Candida albicands에 대해 각각 250 ㎍/mL, 500 ㎍/mL의 생육 억제 농도를 나타내었다. 항보체 활성화능을 측정한 결과 물층 21%를 제외한 다른 분획물은 10% 이하의 낮은 억제효과를 보이거나 활성이 나타나지 않았다. 따라서 괴화추출물은 항산화 활성, 항지질과산화 활성, 항미생물 활성이 우수하였다. 이러한 결과를 바탕으로, 괴화 추출물을 이용하여 식품 및 음료 등과 같은 기능성식품으로서의 다양한 산업적 응용분야에 널리 응용될 수 있을 것으로 생각된다.

Anticancer activity and quantitative analysis of flavone of Cirsium japonicum DC

Cirsium japonicum DC, a traditional Chinese medicine, has been widely used as an antihemorrhagic and diuretic agent. The objective of this study was to perform quantitative analysis of flavone by reversed-phase HPLC and examine the anticancer activity of C. japonicum DC in the S180 and H22 mice. Cirsium japonicum DC was separated and purified with several chromatography techniques and two flavone compounds, pectolinarin and 5,7-dihydroxy-6,4′-dimethoxyflavone, were isolated. The content of these two compounds in the methanol, ethanol, and aqueous extractions respectively was determined by HPLC as follows: pectolinarin 1.87%, 1.65%, 1.27%; 5,7-dihydroxy-6,4′-dimethoxyflavone: 0.515%, 0.42%, 0.221%. Furthermore, the effect of the two flavones on the anticancer activity in S180 and H22 mice was studied. Our research shows that these two flavones greatly inhibit cancer cell growth. The rate of inhibiting S180 mice was 55.77% at 50 mg kg - 1, and the rate of life lengthening was 99.13% at 50 mg kg - 1 in H22 mice.

New Isoflavone Glycoside from the Woods of Sophora japonica.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New Isoflavone Glycoside from the Woods of Sophora japonica

Dept. of Forest Resources, Dongguk University, Seoul 100-715, KoreaReceived September 19, 2003Key Words : Sophora japonica, Leguminosae, 5,6',7-trihydroxy-3',4'-methylenedioxyisoflavone 6'-O-β-D-glycosideSophora japonica L. (Leguminosae), commonly calledScholar Tree, is a well-known traditional medicine used forthe treatment of bleeding and antihemorrhagic agent.

PCV33: COST-ANALYSIS OF CABG SURGERY IN PATIENTS WITH AND WITHOUT RETHORACOTOMY FROM THE HOSPITAL PERSPECTIVE IN GERMANY

OBJECTIVES: German hospitals receive the same reimbursement by the statutory health insurance for CABG surgery irrespective of whether or not a rethoracotomy, which involves higher in-hospital costs, has to be performed following hemorrhage. In order to evaluate the in-hospital costs for CABG with and without rethoracotomy from the hospital perspective, a cost-analysis of CABG surgery was performed. Furthermore, the cost-effectiveness of prophylactic administration of the antihemorrhagic agent aprotinin was investigated. METHODS: The detailed resource utilization of 138 CABG patients, 68 with rethoracotomy and 70 without, was analysed based on sample of patient medical records from 7 German hospitals. Resource costs were provided by hospital administrations and supplemented by literature. The overall costs for both groups were then combined with rethoracotomy rates in patients with and without prophylactic administration of aprotinin derived from a published meta-analysis of all relevant clinical trials in open heart surgery. RESULTS: The total in-hospital costs per patient with CABG were on average DM 21,241 and increased to DM 31,326 for a CABG patient requiring rethoracotomy. Besides the costs of the rethoracotomy, the costs of intensive care were the main cost driver in patients with rethoracotomy. The meta-analysis showed with statistical significance that aprotinin can reduce the rethoracotomy rate from 5.0% to 1.8% in patients undergoing heart surgery. When combining the cost data with the results of the meta-analysis, the expected average costs per patient treated with aprotinin (including drug costs) were DM 21,432 compared to DM 21,655 per patient without aprotinin treatment. A cost-effectiveness analysis (costs per patient without rethoracotomy) resulted in a difference of DM 970 in favour of the prophylactic antihemorrhagic treatment. CONCLUSION: The analysis showed that CABG patients requiring an additional rethoracotomy generated about 47% higher costs than patients with CABG surgery only. The administration of the antihemorrhagic agent aprotinin can be recommended in the light of the reduced complication rate and improved cost-effectiveness of CABG-surgery.

Desmopressin (DDAVP) acts on platelets to generate platelet microparticles and enhanced procoagulant activity

Desmopressin (DDAVP), an analog of vasopressin (AVP), has wide clinical application as an anti-hemorrhagic (AH) agent. DDAVP in vivo releases vWF from endothelial cells but is reported to have little action on platelets. However, DDAVP is often used to improve hemostasis in platelet dysfunctions. We examined the effect of DDAVP on platelet microparticle (PMP) formation and procoagulant activity in vitro using platelets from normal volunteers and in vivo in six patients receiving DDAVP therapy. In the former, platelets were incubated with DDAVP (0.5 to 25 nM) and PMP released were stained with FITC-labeled MAb α-GP IIb IIIa for flow cytometry. Procoagulant activity was measured in a clot-based assay using Russel's viper venom (RVV) calibrated with cephalin. A mean increase of 2–3 fold was observed in both PMP and procoagulant activity. Parallel to these observations was a dose-dependent rise in organelle-associated Ca 2+. The assays were also performed on six patients prior to and at one hour after infusion of DDAVP, and similar but lesser effects were observed. We conclude that DDAVP acts on platelets in vitro, and that these effects may contribute to the hemostatic action of DDAVP in platelet dysfunctions in vivo.