Embrilla has a significant interventional effect on bleeding in the stomach and variceum, and more research on this topic has to be done in the US. To compare this strategy with radiation therapy, randomized trials are necessary [1]. When it comes to the surgical management of symptomatic nephroptosis, the tissue adhesive embuclide seems to be a safe and efficient medication that can produce positive outcomes quickly and easily [2].

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In 80 patients with portal hypertension and patent splenic vein who received endoscopic injection of Enbucrilate mixed 1:1 with ethiodol for gastric variceal bleeding, re-bleeding rates were: 4 of 80 (5%) from 0 to 72 hours; 5 of 76 (6.5%) from >72 hours to 3 months; and 9 of 51 (17%) from >3 months to 1 year. Survival rates after adjusting for dropouts and exclusions were 98% at 72 hours, 84% at 3 months, and 75% at 1 year. Re-bleeding and survival were significantly related to Child-Pugh class. Among 17 deaths, progressive cirrhosis and multi-organ failure was the underlying cause in all, with gastric variceal re-bleeding contributing in 4. [1]

In 12 patients with splenic vein thrombosis (without chronic liver disease), early re-bleeding (0-72 h) occurred in 2 (17%), subacute re-bleeding (>72 h to 3 months) in 1 (8%), and no chronic phase re-bleeding (>3 months to 1 year). One-year survival was 6 (50%) due to underlying malignancy in most. [1]

Metabolism / Metabolites
Organic nitriles are converted into cyanide ions in the liver by cytochrome P450 enzymes. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is primarily metabolized to thiocyanate by thiocyanate oxidase or 3-mercaptopyruvate thiotransferase. Cyanide metabolites are excreted in the urine. (L96)

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Toxicity Summary
Organic nitriles can decompose into cyanide ions both in vivo and in vitro. Therefore, the main toxic mechanism of organic nitriles is the production of toxic cyanide ions, or hydrogen cyanide. Cyanide ions are inhibitors of cytochrome c oxidase in the fourth electron transport chain complex (located on the mitochondrial membrane of eukaryotic cells). It forms a complex with the ferric atom in this enzyme. The binding of cyanide ions to this cytochrome prevents electrons from being transferred from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted, and the cell can no longer perform aerobic respiration to produce ATP for energy. Tissues that rely primarily on aerobic respiration, such as the central nervous system and the heart, are particularly susceptible to this. Cyanide can also produce some toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydrocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinate dehydrogenase, and copper/zinc superoxide dismutase. Cyanide binds to the iron ions in methemoglobin to form inactive methemoglobin cyanide. (L97)

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Serious embolization was suspected in 2 patients (2%). One patient with alcohol-related liver disease and obesity developed cardiac arrest immediately following varix injection and could not be resuscitated (embolization unconfirmed as family declined autopsy). Another patient with hepatitis C cirrhosis, hepatocellular cancer, and portal vein thrombosis suffered a seizure and subsequent lack of movement in the right upper extremity 24 hours after TIPS; a left-sided stroke was seen on CT but no definite radiodense opacities to confirm embolization. [1]

2-3 mm pulmonary opacities were observed in three patients on chest X-ray following injections, without apparent clinical sequelae. [1]

No bleeding from post-injection ulcerations was observed. No cyanoacrylate-related injury to personnel or damage to equipment was observed. [1]

On two occasions, premature polymerization of Enbucrilate in the cannula led to inability to express the polymer and needle puncture bleeding; in both cases, a second application achieved hemostasis. [1]

[1]. Enbucrilate for gastric varices: extended experience in 92 patients. Aliment Pharmacol Ther. 2007 Jul 1;26(1):49-59.

[2]. The use of the tissue adhesive enbucrilate (histoacryl) in the treatment of symptomatic nephroptosis. Urol Int. 2002;69(4):313-7.

Enbucrilate is a nitrile compound and an α,β-unsaturated monocarboxylic acid. Enbucrilate is currently being studied in the clinical trial NCT02468206 (secondary prevention of gastric variceal bleeding). Butyl cyanoacrylate is a cyanide compound. It is the main component of medical cyanoacrylate adhesives used for the adhesion of skin lacerations and the treatment of bleeding in vascular structures. (L595) This is a tissue adhesive that is applied as a monomer to moist tissue and polymerizes to form an adhesive. It is slowly biodegradable and used in various surgical procedures, including dental procedures.

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Enbucrilate (Histoacryl Blue) is a four-carbon cyanoacrylate. It was mixed 1:1 with ethiodol (iodinated poppy seed oil) to delay polymerization. The mixture was prepared by adding 0.5 cc of enbucrilate to 0.5 cc of ethiodol. Injections were performed using a 23-gauge cannula flushed with sterile ethiodol, with about 0.25 cc of glue and 0.25 cc of oil delivered per injection. Sterile water was used as a pusher. Usually 2-4 separate injections were made at the initial session. Antibiotic prophylaxis was routinely administered for 3-5 days following injection. [1]

The study was an FDA-approved pilot investigation (IDE G970157) in 92 patients with gastric variceal bleeding. The majority of patients had portal hypertension (80/92) and fundal varices (GOV2 and IGV1, 66/80). [1]

C8H11NO2

153.18

153.078

6606-65-1

25154-80-7;25154-80-7 (homopolymer);6606-65-1 (Parent)

23087

Colorless to light yellow liquid（Density：0.986 g/cm3）

1.0±0.1 g/cm3

232.8±23.0 °C at 760 mmHg

99.4±0.0 °C

0.1±0.5 mmHg at 25°C

1.443

1.29

0

3

5

11

199

0

O(C(C(C#N)=C([H])[H])=O)C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H]

JJJFUHOGVZWXNQ-UHFFFAOYSA-N

InChI=1S/C8H11NO2/c1-3-4-5-11-8(10)7(2)6-9/h2-5H2,1H3

butyl 2-cyanoprop-2-enoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~652.83 mM)

Solubility in Formulation 1: 2.5 mg/mL (16.32 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (16.32 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (16.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)