104344-23-2 Usage
Uses
Used in Pharmaceutical Industry:
Bisoprolol fumarate is used as an antihypertensive agent for the treatment of essential hypertension. It functions as a selective β1-adrenergic blocker, helping to lower blood pressure and reduce the workload on the heart.
Used in Research and Development:
Labeled Bisoprolol is utilized as an internal standard for the quantification of Bisoprolol by gas chromatography (GC) or liquid chromatography (LC) mass spectrometry. This application aids in ensuring accurate measurements and analysis in research and development settings.
Pharmacological effects
Bisoprolol fumarate is a selective β1-adrenergic receptor blockers. No intrinsic sympathomimetic activity and membrane stabilizing effect. Animal experiments of different models show that affinity for β1-receptor is 11 to 34-fold larger than β2-receptor. The selectivity for β1 receptor is four times of the similar drugs Atenolol. This product plays the role for a long time (24 hours or more), continual application takes good control of symptoms without tolerance phenomenon, with minimal side effects on the respiratory system, no effects on metabolism of fat. it also has a certain degree of block effect for bronchial β2 receptors, but it may only occur at high doses, usually it has no obvious clinical significance.
Indications
Treatment of essential hypertension. As first-line antihypertensive agents, it can be used alone or combined with diuretics and vasodilator drugs.
Angina and myocardial infarction.
Arrhythmias, such as the rapid ventricular arrhythmia, ventricular contraction.
In recent years, bisoprolol fumarate is also tempted used for the treatment of heart failure. It is effective for moderate to severe chronic stable heart failure which previously receiving ACE inhibitors, diuretics and cardiac glycosides medications associated with ventricular systolic dysfunction (ejection fraction ≤35%) .
The above information is edited by the lookchem of Tian Ye.
Method and Dosage
Hypertension: The initial dose is 5mg once, 1 times a day. It may be suitable for some patients to start with initial dose of 2.5mg (such as bronchial spasm disease). If the dose of 5 mg one day is not enough for antihypertensive effect , the dose may be increased to 10-20mg one day .
Angina: initial dose of 2.5mg, 1 time a day, the maximum daily dose can not exceed 10mg.
Heart failure: chronic, stable heart failure: it should start from small dose, if it is tolerated, the dose can gradually increasing (doubling the dose every 2-4 weeks) to the maximum tolerated dose or target dose. The maximum recommended target dose is 10mg one day , the starting dose is usually 1/8 of the target dose.
Distinguish
Take appropriate amount of this product powder (about the equivalent of bisoprolol fumarate 20mg), add 4ml water to dissolve, the filtrate is added 1 to 3 drops of potassium permanganate test solution , purple should fade , and brown precipitate forms.
Take right amount of this product powder,it is dissolved in water and form the solution of which 1ml each contains about 0.1mg bisoprolol fumarate,after filtration, take continued filtrate, according to the UV-visible spectrophotometry (Appendix Ⅳ A) measure ,there is the maximum absorption in the 271nm wavelength.
In the chromatogram recorded under the item of content determination ,the test solution peak retention time should be consistent with the reference solution peak retention time.
Content Determine
Take 10 tablets of this product , weigh accurately, porphyrize, accurately weigh appropriate amount (about the equivalent of bisoprolol fumarate 5mg), set it into 50ml volumetric flask, add water to make bisoprolol fumarate dissolve and dilute it to the mark , shake, filtrate, according to chromatographic conditions under the item of bisoprolol fumarate related substances,take the precise amount of continued filtrate 20μl into the liquid chromatograph, record the chromatograms; in addition , precisely weigh appropriate amount of the reference bisoprolol fumarate , dissolve it in water and dilute into the solution of which 1ml each contains about 0.1mg,measure in the same method, calculate according to the external standard method bisoprolol peak area ,it is obtained .
Drug interactions
1.when bisoprolol fumarate is used in combination with other anti-hypertensive drugs, the antihypertensive effect is enhanced .
2. when bisoprolol fumarate is used in combination with reserpine, methyldopa, clonidine or guanfacine, the heart rate can be slowed down.
3. when bisoprolol fumarate is used in combination with reserpine, reserpine needs to be stopped a few days after stop of this product .
4. when bisoprolol fumarate is used in combination with nifedipine, the antihypertensive effect of this product can be enhanced .
5. when bisoprolol fumarate is used in combination with verapamil or diltiazem ketones calcium icon antagonists or other antiarrhythmic drugs , there is the need for patient care, because they can cause hypotension, bradycardia and others.
Drug interactions
Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect.
Analgesics: NSAIDs antagonise hypotensive effect.
Anti-arrhythmics: increased risk of myocardial
depression and bradycardia; increased risk of
bradycardia, myocardial depression and AV block
with amiodarone; increased risk of myocardial
depression and bradycardia with flecainide.
Antibacterials: concentration reduced by rifampicin.
Antidepressants: enhanced hypotensive effect with
MAOIs.
Antihypertensives; enhanced hypotensive effect;
increased risk of withdrawal hypertension with
clonidine; increased risk of first dose hypotensive
effect with post-synaptic alpha-blockers such as
prazosin.
Antimalarials: increased risk of bradycardia with
mefloquine.
Antipsychotics enhanced hypotensive effect with
phenothiazines.
Calcium-channel blockers: increased risk of
bradycardia and AV block with diltiazem;
hypotension and heart failure possible with
nifedipine and nisoldipine; asystole, severe
hypotension and heart failure with verapamil.
Cytotoxics: possible increased risk of bradycardia
with crizotinib.
Diuretics: enhanced hypotensive effect.
Fingolimod: possibly increased risk of bradycardia.
Moxisylyte: possible severe postural hypotension.
Sympathomimetics: severe hypertension with
adrenaline and noradrenaline, and possibly with
dobutamine.
Precautions
Diabetic patients with great blood glucose fluctuations or acidosis patients should be careful in use of it.
Patients with pulmonary insufficiency, severe liver and kidney dysfunction should use with caution.
Interruption of treatment should diminish doses daily ,when it is used in combination with other antihypertensive drugs, the dose often requires reductions.
when drug overdose causes slow heartbeat or low blood pressure , patients must immediately stop taking this product. If necessary, take separate or sequential use of following drugs, atropine 0.5mg~2.0mg intravenously, appropriate amount of metaproterenol slow intravenous injection; glucagon 1mg~5mg (or 1mg~10mg).
Because the antihypertensive effect of bisoprolol fumarate, capacity of the patient to drive or operate the machine may be weakened , particularly at the beginning of taking medication or conversion medication and taking with alcohol at the same time, but the person's ability to respond will not be directly affected .
Side effects
1.In early medication, mild fatigue, chest tightness, dizziness, bradycardia, drowsiness, palpitations, headache and lower limb edema may appear , and all automatically reduce or disappear after continuing taking .
2. In rare cases, there will be gastrointestinal disorders (diarrhea, constipation, nausea, abdominal pain) and skin reactions (eg erythema, itching).
3. Occasionally blood pressure decreases , pulse slow or atrioventricular conduction disorders.
4.Sometimes there will be tingling or cold extremities, in rare cases, it can cause muscle weakness, muscle cramps and less tears.
5.For patients with intermittent claudication or Raynaud's phenomenon,during the initial medication, the condition may worsen, the condition of existing myocardial dysfunction patients will possibly aggravate.
6.Occasionally airway resistance may increase .
7.Elderly patients with diabetes, their glucose tolerance may reduce , which may cover hypoglycemia manifestations (such as rapid heartbeat).
Toxicity
Moderate poisoning
Acute toxicity
Oral-rat LD50: 940 mg/kg; Oral-Mouse LD50: 678 mg/kg
Flammability hazard characteristics
Combustible; fire decomposition with toxic nitrogen oxide fumes
Storage Characteristics
Treasury temperature, ventilation, dry
Extinguishing agent
Water, carbon dioxide, dry, sandy soil
Originator
E. Merck (W. Germany)
Manufacturing Process
A solution of 10 g of 1-(p-2-isopropoxyethoxymethylphenoxy)-3-isopropylideneamino-propan-2-ol [obtainable by reacting 1-(p-2-
isopropoxyethoxymethylphenoxy)-2,3-epoxy propane with ammonia to give 1-
(p-2-isopropoxyethoxymethylphenoxy)-3-amino-propan-2-ol and subsequently
reacting this with acetone] in 250 ml of ethanol was hydrogenated on 0.5 g of
Raney nickel at 25°C under 1 atmosphere of pressure until 1 equivalent of H2
had been absorbed. The mixture was filtered and the filtrate evaporated to
give 1-(p-2-iso-propoxyethoxymethyl-phenoxy)-3-isopropylamino-propan-2-ol,
fumarate, m.p. 100°C (after addition of equimolecular quantity of fumaric
acid).
Therapeutic Function
Beta-adrenergic blocker
Biological Activity
A selective β 1 -adrenergic antagonist. Has a K d of 2-3 nM at the β 1 receptor and a β 1 / β 2 selectivity of approximately 100-fold.
Biochem/physiol Actions
Bisoprolol hemifumarate is useful in oral formulations due to its high bioavailability. It also shows long elimination half-life.
Clinical Use
Beta-1 adrenoceptor blocker:
Hypertension
Angina
Adjunctive treatment for heart failure
Metabolism
Bisoprolol is excreted from the body by two routes. 50%
is metabolised by the liver to inactive metabolites which
are then excreted by the kidneys. The remaining 50% is
excreted by the kidneys in an unmetabolised form.
Check Digit Verification of cas no
The CAS Registry Mumber 104344-23-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,4,3,4 and 4 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 104344-23:
(8*1)+(7*0)+(6*4)+(5*3)+(4*4)+(3*4)+(2*2)+(1*3)=82
82 % 10 = 2
So 104344-23-2 is a valid CAS Registry Number.
InChI:InChI=1/C18H31NO4.C4H4O4/c1-14(2)19-11-17(20)13-23-18-7-5-16(6-8-18)12-21-9-10-22-15(3)4;5-3(6)1-2-4(7)8/h5-8,14-15,17,19-20H,9-13H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b;2-1+
104344-23-2Relevant articles and documents
Polymorphic forms of bisoprolol fumarate: Preparation and characterization
Detrich, ádám,D?m?t?r, Kata Judit,Katona, Miklós Tamás,Markovits, Imre,Vargáné Láng, Judit
, (2018/07/30)
Bisoprolol fumarate is a beta blocker-type drug substance which has been well known for several decades. However, no relevant data can be found in the literature about its crystal polymorphism. The purpose of this paper was to present two anhydrous forms (Form I and Form II) and a hydrate of bisoprolol fumarate substance. Crystalline forms were studied by various solid-state analytical methods: Fourier transform infrared (FT-IR) spectroscopy, X-ray powder diffraction (XRPD), dynamic vapor sorption (DVS) and thermoanalytical methods (thermogravimetry and differential scanning calorimetry). Thermodynamic stability and solubility of the presented polymorphs were also investigated. Both FT-IR and XRPD methods were found to be suitable for the characterization of the different crystal structures. Thermoanalytical measurements showed that (1) Form I and Form II own clearly different melting points and (2) both Form II and hydrate forms can transform into Form I at higher temperature values. Results of the DVS measurements prove that both Form I and Form II became metastable under extremely humid conditions (> 80% RH) and converted into the hydrate. Thermodynamic stability studies showed that Form I and Form II polymorphs are in enantiotropic relationship with an enantiotropic point at about 40–45?°C. Solubility studies indicated that all of the prepared forms are highly soluble, and no difference was found between them. Considering the recommendations of the corresponding International Conference of Harmonization guideline, it can be stated that no specification is required for crystal polymorphism in case of this substance.
A NOVEL PROCESS FOR THE SYNTHESIS OF BISODPROLOL AND ITS INTERMEDIATE
-
Page/Page column 5; 9-10, (2010/11/27)
This invention relates to a manufacturing process for the preparation of bisoprolol and its pharmaceutically acceptable salt as well as its intermediates. The intermediate 4-[(2-isopropoxyethoxy)methyl]phenol is prepared by reaction of 4-hydroxybenzyl alcohol with 2-isopropoxy ethanol in presence of Amberlyst 15 in high yield with high purity.
Controlled release pharmaceutical preparation
-
, (2008/06/13)
A controlled release pharmaceutical preparation comprising a core containing a medicinal compound and a coating layer containing a water-repellent salt and a water-insoluble and slightly water-permeable acrylic polymer having trimethylammoniumethyl group. Said preparation releases a medicinal compound in a sigmoid type dissolution pattern irrespective of the PH of a dissolution medium.
