Obstetric hemorrhage is the leading cause of maternal morbidity and mortality worldwide. Uterine atony leading to postpartum hemorrhage (PPH) is the most common type seen [1]. Other factors include genital tract lacerations, retained placenta, uterine inversion, and acquired or inherited coagulopathy. The World Health Organization defines PPH as a blood loss in excess of 500 mL after delivery; the common sites for blood loss include the uterus, cervix, vagina, and perineum [2]. Massive PPH (> 1 L) accounts for > 10% of all maternal deaths and can lead to permanent morbidity [3]. Therapeutic management strategies include uterine compression with massage or manual compression, compression sutures (B-Lynch procedure), increasing intrauterine pressure with balloon catheters or gauze packing, and/or uterotonic agents or intravenous hemostatic agents such as tranexamic acid (Transamin) and recombinant activated blood factor VIIa (rfVIIa) [4]. We describe a case of refractory massive PPH. The bleeding persisted even though vaginal packing and uterine artery embolization were administered. Disseminated intravascular coagulation (DIC) then developed, which we successfully corrected with two injections of rfVIIa. Interventions with rfVIIa in cases of PPH have been reported in the past decade. The first report of the use of rfVIIa in an obstetric patient with DIC following PPH was by Plaat [5] in

01 Dec 2011·Advances in Medical SciencesQ4 · MEDICINE

The effect of ε-aminocaproyl-S-benzyl-L-cysteine on the t-PA activity of human saliva

Q4 · MEDICINE

Article

Author: K Midura-Nowaczek ; J Kaczyńska ; I Bruzgo ; A Markowska ; D Drozdowska

PURPOSEThe aim of this work was to study the effect of the synthetic antifibrinolytics: ε-aminocaproic acid (EACA), tranexamic acid (AMCHA) and ε-aminocaproyl-S-benzyl-L-cysteine (H-EACA-S-Bzl-L-Cys-OH) on the fibrinolytic activity of saliva in order to obtain new data on the activity of saliva tissue plasminogen activator (t-PA).MATERIAL AND METHODSSaliva samples were obtained from healthy volunteers. Saliva, precipitate and supernatant were tested 1hr, 4 hrs and 6hrs after collection. The effect of the synthetic antifibrinolytics was examined with the use of the clot lysis time determination.RESULTSAll examined compounds inhibited the fibrinolytic activity of saliva 1hr after collection. H-EACA-S-Bzl-L-Cys-OH was the most active inhibitor. After 6 hours in room temperature only this compound showed a certain possibility to prolong the clot lysis time.CONCLUSIONSThe obtained results may indicate the possibility of the difference in specificity between the activities of t-PA of saliva and recombinant tissue plasminogen activator activities. It may explain the unexpected high inhibitory activity of H-EACA-S-Bzl-L-Cys-OH in our study.

01 Jul 2008·Russian Journal of Bioorganic Chemistry

The in vitro cross-effects of inhibitors of renin-angiotensin and fibrinolytic systems on the key enzymes of these systems

Article

Author: O. A. Kost ; L. I. Mukhametova ; I. I. Nikolskaya ; P. V. Binevski ; R. B. Aisina ; D. A. Gulin

The effects of hypotensive agents (captopril, enalaprilate, and lisinopril) on the activities of components of the fibrinolytic system (FS) and the effects of antifibrinolytic agents (6-aminohexanoic acid (6-AHA) and tranexamic acid (t-AMCHA)) on the activities of angiotensin converting enzyme (ACE) were studied in vitro. Enalaprilate did not affect the FS activity. Captopril considerably inhibited the amidase activities of urokinase (u-PA), plasminogen tissue activator (t-PA), and plasmin ([I]50 (2.0-2.6) +/- 0.1 mM), and the activation of Glu-plasminogen affected by t-PA and u-PA ([I]50 (1.50-1.80) +/- 0.06 mM), which may be due to the presence of a mercapto group in the inhibitor molecule. Lisinopril did not affect the amidase activities of FS enzymes, but stimulated Glu-plasminogen and u-PA activation and inhibited activation of t-PA-fibrin-bound Glu-plasminogen ([I]50 (12.0 +/- 0.5) mM). Presumably, these effects can be explained by the presence in lisinopril of a Lys side residue, whose binding to lysine-binding Glu-plasminogen centers resulted, on the one hand, in the transformation of its closed conformation to a semi-open one and, on the other hand, in its desorption from fibrin. Unspecific inhibition of the activity of ACE, a key enzyme of the renin-angiotensin system, in the presence of 6-AHA and t-AMCHA ([I]50 10.0 +/- 0.5 and 7.5 +/- 0.4 mM, respectively) was found. A decrease in the ACE activity along with the growth of the fibrin monomer concentration was revealed. The data demonstrate that, along with endogenous mediated interactions, relations based on the direct interactions of exogenous inhibitors of one system affecting the activities of components of another system can take place.

News (Medical) associated with XP-27B

10 Aug 2023

·www.pharmaceutical-technology.com

Palisade Bio terminates its post-surgical abdominal adhesions treatment trial

Phalguni Deswal @Phalguni_GD Tranexamic acid is also under development for post-operative ileus, and accelerating the return of bowel function post-abdominal surgery. Image Credit: Buravleva stock / Shutterstock. Palisade Bio has terminated the development of its lead clinical candidate, tranexamic acid (LB1148), for reducing intra-abdominal adhesions in patients after elective bowel resection surgery. The news led to a sharp 69% decline in Palisade’s stock at market open on 9 August, compared to market close on the previous day. The company’s market cap stands at $4.8m. Recommended Reports Reports LOA and PTSR Model - Rezvilutamide in Liver Failure (Hepatic Insufficiency) GlobalData Reports LOA and PTSR Model - Aramchol in Liver Failure (Hepatic Insufficiency) GlobalData View all Companies Intelligence Palisade Bio, Inc Palisade Corp View all Tranexamic acid is a broad-spectrum serum protease inhibitor . It reduces damage to the intestine by neutralising digestive enzymes. The drug was investigated for the indication in a randomised, placebo-controlled, multicentre Phase II clinical trial (NCT02836470) that failed to meet its primary endpoint. Furthermore, 16 serious adverse events were observed in the tranexamic acid group, compared to 14 events in the placebo group, as per the press release . The clinical trial was wrought with difficulties. It was paused in July 2020 due to Covid-19, leading to low patient recruitment. After its restart in May 2022, the study’s protocol was changed to investigate the use of LB1148 in reducing adhesions from its original indication of the return of gastrointestinal function in patients post-elective bowel resection surgery. Tranexamic acid is also under development for post-operative ileus and accelerating the return of bowel function post-abdominal surgery . Palisade has a development and licencing agreement with Newsora for the tranexamic acid programme in China. The agreement grants Palisade clinical, regulatory, and commercial milestone-based payments, as well as tiered royalty payments for net annual sales in greater China. Palisade reduced its workforce by 30% at the start of 2023, as part of a cost-reduction strategy. As per the company’s 2022 financial report , it has cash reserves of $12.4m to fund its operation to mid-2024.

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Indication	Highest Phase	Country/Location	Organization	Date
Menorrhagia	Discovery	US	XenoPort, Inc.	-
Menorrhagia	Discovery	US	XenoPort, Inc.	-
Menorrhagia	Discovery	US	Xanodyne Pharmaceuticals, Inc.	-
Menorrhagia	Discovery	US	Xanodyne Pharmaceuticals, Inc.	-

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