What Is Tranexamic Acid?

Tranexamic acid, also known as tranexamic acid, chemical name is trans-4-aminomethylcyclohexanecarboxylic acid, white crystalline powder; odorless, slightly bitter. Soluble in water, almost insoluble in ethanol, acetone, chloroform or ether. The molecular formula is C8H15NO2, the molecular weight is 157.21000, the density is 1.095 g / cm3, the melting point is 233ºC, and the boiling point is 300.2ºC at 760 mmHg.

Tranexamic acid, also known as tranexamic acid, chemical name is trans-4-aminomethylcyclohexanecarboxylic acid, white crystalline powder; odorless, slightly bitter. Soluble in water, almost insoluble in ethanol, acetone, chloroform or ether. The molecular formula is C8H15NO2, the molecular weight is 157.21000, the density is 1.095 g / cm3, the melting point is 233ºC, and the boiling point is 300.2ºC at 760 mmHg.

Chinese name

Tranexamic acid

English name

Tranexamic Acid

nickname

Tranexamic acid, tranexamic acid, tranexamic acid

Chemical formula

C8H15NO2

Molecular weight

157.21

CAS Registry Number

1197-18-8

EINECS registration number

214-818-2

Melting point

233ºC

Boiling point

300.2ºC at 760 mmHg

Water soluble

Water soluble

Density

1.095 g / cm3

Exterior

White powder

Flash point

135.4ºC

Application

Whiten and freckle, stop bleeding

Place of Origin

Yingcheng, Hubei

Introduction to Tranexamic Acid Compounds

Tranexamic acid basic information

Chinese name: Tranexamic acid

Chinese alias: tranexamic acid; tranexamic acid (4-aminomethylcyclohexanoic acid); 4- (aminomethyl) cyclohexanoic acid;

English name: Tranexamic acid

English alias: 1- (biphenyl-4-yl) methanamine; 4-carboxycyclohexylmethylamine; (4-phenylphenyl) methylamine; 4-aminomethylcyclohexane carboxylic acid; 4-Biphenylmethylamine;

CAS number: 701-54-2

Molecular formula: C ₈ H ₁₅ NO ₂

Molecular weight: 157.21000

Structural formula:

Exact mass: 157.11000

PSA: 63.32000

LogP: 1.53640 ^[1]

Tranexamic acid physicochemical properties

Density: 1.095 g / cm ³

Melting point: 233ºC

Boiling point: 300.2ºC at 760 mmHg

Flash point: 135.4ºC

Storage conditions: refrigerated ^[1]

Tranexamic acid toxicology data

1. Acute toxicity: Rat (oral) LD50:> 15mg / kg Rat (venous) LD50: 1,800mg / kg mouse (oral) LD50:> 15mg / kg mouse (venous) LD50: 1,600 mg / kg

Since the LD50 of common salt is 3,000 mg / kg, the acute toxicity of BPA is the same as that of common salt. ^[2]

Tranexamic acid molecular structure data

1. Molar refractive index: 42.00

2. Molar volume (m3 / mol): 143.4

3. Isometric Zhang Rong (90.2K): 368.6

4. Surface tension (dyne / cm): 43.6

5. Polarization rate: 16.65 ^[2]

Tranexamic acid calculated chemical data

1. Reference value for calculation of hydrophobic parameters (XlogP): -2

2. Number of hydrogen-bonded donors: 2

3. Number of hydrogen bond acceptors: 3

4. Number of rotatable chemical bonds: 2

5. Topological molecular polar surface area (TPSA): 63.3

6. Number of heavy atoms: 11

7. Surface charge: 0

8. Complexity: 139

9. Number of isotope atoms: 0

10. Determine the number of atomic stereocenters: 0

11. Uncertain number of atomic stereocenters: 0

12. Determine the number of chemical bond stereocenters: 0

13. Uncertain number of chemical bond stereocenters: 0 ^[2]

14. Number of covalent bond units: 1

Tranexamic Acid Pharmacopoeia Standard

The main chemical components of tranexamic acid

This product is trans-4-aminomethylcyclohexane. Calculated based on dry products, containing C8H15NO2 shall not be less than 99.0%. ^[3]

Tranexamic acid

White crystalline powder; odorless, slightly bitter.

Soluble in water, almost insoluble in ethanol, acetone, chloroform or ether. ^[3]

Tranexamic acid identification

(1) Take about 0.1g of this product, add 5ml of water to dissolve, add about 10mg of ninhydrin, heat, and gradually become blue-violet.

(2) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 409). ^[3]

Tranexamic acid test

Alkalinity

Take 0.5g of this product, add 10ml of water to dissolve, and measure according to law. The pH value should be 7.0 8.0.

Clarity and color of the solution

Take 1.0g of this product and add 20ml of water to dissolve. The solution should be clear and colorless.

chloride

Take 0.50g of this product and check it according to law. Compared with the control solution made of 7.0ml of standard sodium chloride solution, it must not be more concentrated (0.014%).

Sulfate

Take 0.50g of this product and check according to law. Compared with the control solution made of 3.5ml of standard potassium sulfate solution, it must not be more concentrated (0.07%) (for oral or injection) or the control solution made of 2.0ml of standard potassium sulfate solution. For comparison, it must not be more concentrated (0.04%) (for intravenous infusion). ^[3]

relative substance

Take this product, add water to dissolve and quantitatively dilute it to make a solution containing about 10mg of tranexamic acid per 1ml as the test solution; take 1ml precisely, place it in a 200ml volumetric flask, dilute to the mark with water, and shake as Control solution. According to the high performance liquid chromatography (2010 edition Pharmacopoeia Part II Appendix V D) test, using octadecylsilane bonded silica as a filler, 0.23% sodium dodecyl sulfate solution (take 18.3 g of sodium dihydrogen phosphate, Add 800ml of water to dissolve, add 8.3ml of triethylamine and mix well, then add 2.3g of sodium lauryl sulfate, shake to dissolve, adjust the pH to 2.5 with phosphoric acid, add water to 1000ml, shake)-methanol (60: 40) is mobile phase, the detection wavelength is 220nm. Dissolve and dilute tranexamic acid and tranexamic acid in water and dilute to make a solution containing 0.2mg of tranexamic acid and 2g of tranexamic acid per 1ml. Take 20l into the liquid chromatograph, adjust the flow rate, and make the tranexamic acid peak. The retention time is about 13 minutes, and the resolution of the tranexamic acid peak and the glutamic acid peak should be greater than 5.0. Take 20 l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 10% of the full scale. Then, 20 l of each of the test solution and the control solution was accurately measured, and injected into the liquid chromatograph respectively, and the retention time of the chromatogram to the main peak was recorded three times. If there is an impurity peak in the chromatogram of the test solution, the area of the cyclic olefin impurity peak with a relative retention time of about 1.2 times the correction factor of 0.005 must not be greater than 0.2 times (0.1%) the main peak area of the control solution; After the correction factor 0.006, it must not be greater than 0.2 times (0.1%) the main peak area of the control solution; after the Z-isomer peak area with a relative retention time of about 1.5 times the correction factor 1.2, it must not be greater than 0.4 times (0.2 times the main peak area of the control solution). %), The peak area of other single impurities should not be greater than 0.2 times (0.1%) of the main peak area of the control solution, and the sum of the peak areas of cycloolefin, aminic acid, and Z-isomer should be multiplied by the correction factor and the area of other impurity peaks. Greater than the area of the main peak of the control solution (0.5%). ^[3]

Easy carbonization

Take 0.50g of this product and check it according to law (Appendix O of Part Two of the 2010 Pharmacopoeia). If color develops, compare with the control solution [yellow-green or orange-yellow colorimetric solution diluted 1 times with water (Appendix Part Two of the 2010 Pharmacopoeia) A first method)] comparison must not be deeper.

Loss on drying

Take this product and dry it at 105 to constant weight, and the weight loss shall not exceed 0.5%.

Residue on ignition

Take 1.0g of this product and inspect it according to law. The residual residue should not exceed 0.1%.

Barium salt

Take 1.0g of this product, add 20ml of water to dissolve (if the solution is not clear, filter), divide into 2 equal parts: add 1ml of dilute sulfuric acid; add 1ml of water to the other, let stand for 15 minutes, the two solutions should be the same clarify.

Heavy metal

Take the residue left under the item of burning residue and inspect it according to law. The content of heavy metals must not exceed 10 parts per million. ^[3]

Determination of Tranexamic Acid

Take about 0.12g of this product and accurately weigh it. After dissolving in 40ml of glacial acetic acid, add 1 or 2 drops of crystal violet indicator solution. Titrate with perchloric acid titration solution (0.1mol / L) until the solution becomes blue-green, and titrate The results are corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 15.72mg of C8H15NO2. ^[3]

Description of Tranexamic Acid Related Drugs

Tranexamic acid drug name

[Common name] Tranexamic acid tablets

[Product Name] Tosamin Transamin

[English name] Tranexamic Acid Tablets

[Chinese Pinyin] An Jia Huan Suan Pian ^[4]

Tranexamic acid ingredients

The main ingredient of this product is tranexamic acid. Its chemical name is: (E) -4-aminomethylcyclohexanecarboxylic acid.

Molecular formula: C8H15N02

Molecular weight: 157.21 ^[4]

Tranexamic acid category

Chemicals & Biological Products >> Blood System Drugs >> Procoagulants >> Antifibrinolytic Drugs

Chemical Medicine and Biological Products >> Obstetrics and Gynecology >> Other Gynecologicals

Tranexamic acid

This product is a white film-coated tablet (shaped film). ^[4]

Tranexamic acid pharmacology and toxicology:

Fibrinolysis is related to the breakdown of fibrin and increased vascular permeability of the body under physiological or pathological conditions. It is also related to the development and healing of body reactions, various bleeding symptoms and allergies caused by fibrinolysis. Tranexamic acid can inhibit the action of this plasmin, and shows hemostatic, anti-allergic and anti-inflammatory effects.

1. Antiplasmin

   Tranexamic acid can strongly adsorb to the lysine binding site (LBS) of the fibrin affinity site on plasmin and plasminogen, which inhibits the binding of plasmin, plasminogen and fibrin, thereby Strongly inhibits fibrinolysis caused by plasmin. In addition, in the presence of antifibrinolytic enzymes such as 2 macroglobulin in serum, the antifibrinolytic effect of tranexamic acid is more obvious, and the hemostatic effect is more significant.

2. Plasminase, which is abnormally hyperactive in hemostasis, will cause platelet aggregation inhibition and decomposition of coagulation factors. Mild hypersensitivity first results in the breakdown of fibrin. Therefore, it is considered that in general bleeding, tranexamic acid can inhibit fibrin decomposition and play a hemostatic effect.

3. Anti-allergic and anti-inflammatory effects Tranexamic acid can inhibit the production of kinins and other active peptides (guinea pigs, rats) that cause enhanced vascular permeability, allergies and inflammatory lesions. ^[4]

Tranexamic acid pharmacokinetics:

1. Blood concentration

   The pharmacokinetic parameters of a single dose (500mg tablets) of this product for oral administration in healthy adults are as follows:
   Pharmacokinetic parameters of tranexamic acid in a single dose (500mg) when administered orally (n = 5)

2. When a single dose of C-tranexamic acid is administered orally to rats, the concentration in most organs is the same as the total blood concentration, and the highest concentration is shown 2 hours after administration; the blood concentrations of kidney and liver are in the blood, other The blood concentration of the organ is lower than the blood. ^[4]

3. Metabolism and excretion A single dose of 500 mg or 250 mg of tranexamic acid tablets in healthy adults is quickly absorbed. Twenty-four hours after the administration, 40-70% of the dose was excreted in the urine as a prototype.

Tranexamic acid indication

This product can be used for:

1. Prostate, urethra, lung, brain, uterus, adrenal gland, thyroid, liver and other organs rich in plasminogen activator trauma or surgical bleeding.

2. Used as a thrombolytic agent, such as tissue-type plasminogen activator (t-PA), antagonist of streptokinase and urokinase.

3. Fibrinolytic hemorrhage caused by abortion, early placental exfoliation, stillbirth and amniotic fluid embolism.

4. Menstrual bleeding with increased local fibrinolysis, anterior chamber bleeding, and severe nosebleeds.

5. It is used to prevent or reduce bleeding after extraction of teeth or oral surgery in patients with hemophilia with factor or factor deficiency.

6. Mild bleeding caused by rupture of central aneurysm, such as subarachnoid hemorrhage and intracranial aneurysm bleeding, the use of this product to stop bleeding is better than other antifibrinolytic drugs, but you must pay attention to the risk of concurrent cerebral edema or cerebral infarction . As for patients with severe indications for surgery, this product can only be used as an adjuvant.

7. Used to treat hereditary angioedema, which can reduce the number and severity of attacks.

8. Active hemorrhage occurs in patients with hemophilia. ^[4]

9. Have exact effect on melasma.

Tranexamic acid usage dosage

Intravenous infusion: Generally adults 0.25 0.5g once, if necessary, 1 2g daily, divided into 1-2 times. Depending on age and symptoms, the dosage can be increased or decreased appropriately, or as directed by your doctor.

To prevent bleeding before and after surgery, you can refer to the above dose. Treatment of bleeding caused by primary fibrinolysis. The dose can be increased as appropriate. ^[4]

Tranexamic acid adverse reactions

In a report of 2954 cases, the main adverse reactions were: loss of appetite 0.61% (18 cases), nausea 0.41% (12 cases), vomiting 0.20% (6 cases), heartburn 0.17% (5 cases), itching 0.07% (2 cases), rash 0.07% (2 cases), etc.
When the following adverse reactions occur, the drug should be stopped and treated appropriately:

If any adverse events and / or adverse reactions occur during the use of this product, the doctor should be informed. ^[4]

Tranexamic acid contraindications

1. Those who are allergic to any of the ingredients in this product are prohibited. 2. Disable patients who are using thrombin. (Please refer to "drug interaction") ^[4]

Tranexamic acid precautions

1. The following patients should be administered with caution

   (1) Patients with thrombosis (cerebral thrombosis, myocardial infarction, thrombophlebitis, etc.) and patients who may cause thrombosis. [There is a tendency to stabilize the thrombus]
   (2) Patients with wasting coagulopathy. (Combined with heparin, etc.) [There is a tendency to stabilize blood clots]
   (3) Patients who are in bed after surgery and patients who are undergoing compression hemostasis. [The above conditions are prone to venous thrombosis, and there is a tendency to stabilize the thrombus after administration of this drug. Pulmonary embolism has been reported after getting out of bed and after decompression.
   (4) Patients with renal insufficiency [Sometimes blood concentration rises]
   (5) Patients with a previous history of allergies to this agent.

2. Guidance on medication: Tell patients to take the tablets from the PTP board and then take them (reported by the accidental ingestion of the PTP board, the hard acute angle penetrated into the esophagus mucosa, which led to more severe perforation and caused severe complications such as mediastinal sinusitis) . ^[4]

Tranexamic acid medication for pregnant and lactating women

A small amount of data on the use of tranexamic acid during pregnancy shows that this product is not harmful to the fetus.

There are no clinical trial data of this product for pregnant women. Pregnant women use this product with caution.

There are no clinical trial data of this product for lactating women. Due to the low concentration of tranexamic acid in breast milk (only one percent of the blood), infants absorb very little medicine from breast milk daily. When really needed, pregnant women in lactating women should use this product according to doctor's advice.

Tranexamic acid for children

There are no clinical trial data for this product in children. When really needed, you should use this product according to your doctor's advice.

Tranexamic acid medication for the elderly

In general, elderly patients should reduce the amount of medication due to physiological decline.

Tranexamic acid drug interactions

As shown in the figure:

Tranexamic acid overdose

It has been reported that long-term administration to dogs can cause retinopathy. ^[4]

Studies and reports of overdose of this product are still lacking. Once overdose occurs, symptomatic and supportive treatment should be given.

Tranexamic acid expert reviews

Its hemostatic mechanism is the same as that of aminocaproic acid and aminotoluic acid. Longer hold time. It can be used for bleeding caused by acute, chronic, localized or systemic hyperfibrinolysis. For central nervous system bleeding, such as subarachnoid space and intracranial aneurysm bleeding, this product is better than other antifibrinolytic drugs. In addition, the secondary hyperfibrinolysis caused by disseminated intravascular coagulation should be used with caution before heparinization. ^[5]

Tranexamic acid clinical use

Tranexamic acid wound

Studies have shown that tranexamic acid can safely and reliably reduce mortality in patients with traumatic bleeding. In view of this, tranexamic acid, a cheap, generic drug, has been included in the WHO essential medicine list and will be widely used in high, middle and low income countries around the world.

Tranexamic acid brain injury

Studies have shown that patients with traumatic brain who receive tranexamic acid may experience progressive bleeding and a reduction in mortality.

Although neither of these studies has reached a very clear conclusion, it still suggests that tranexamic acid may improve the prognosis of traumatic brain injury, which will lay the foundation for subsequent research, such as the upcoming implementation and recruitment of up to 10,000 skulls The CRASH-3 study in patients with brain injury will provide solid evidence for the efficacy of tranexamic acid in improving mortality and disability.

Tranexamic acid

Tranexamic acid can significantly reduce blood loss in women with excessive menstrual blood. A Cochrane systematic review evaluating antifibrinolytic drugs (mainly tranexamic acid) for treating excessive menstrual bleeding points out that antifibrinolytic preparations can reduce the blood volume of women with more menstrual periods than placebo or other Loss without increasing the incidence of side reactions. The US Food and Drug Administration has approved the use of tranexamic acid oral tablets as a treatment for women with severe menstrual bleeding on November 13, 2009.

Tranexamic acid postpartum hemorrhage

Studies have shown that tranexamic acid significantly reduces postpartum hemorrhage. However, due to the lower methodological quality of the three randomized trials included, there is no evidence from high-quality studies to support the use of antifibrinolytic drugs in postpartum hemorrhage. Currently, a randomized double-blind placebo-controlled trial called WOMAN (The World Maternal Antifibrinolytic Trial) is underway. It will recruit 15,000 patients worldwide for early application of tranexamic acid for mortality and hysterectomy in patients with postpartum hemorrhage Provide solid evidence for improvements such as rates.

Tranexamic acid surgery

A Cochrane systematic review that included 65 randomized controlled trials showed that tranexamic acid reduced the risk of postoperative blood transfusion by nearly a third (RR 0.61, 95% CI 0.53 to 0.70), and reduced intraoperative and postoperative The amount of bleeding and the incidence of thromboembolic events did not increase.

Other therapeutic effects of tranexamic acid

Tranexamic acid is also used as a second-line treatment for adjuvant treatment of patients with hemophilia with factor deficiency before and after surgery. It can also be used for hereditary angioedema.

Tranexamic acid whitening effect

Its effect of removing dark spots and spots is about 50 times higher than that of vitamin C and about 10 times that of fruit acid.