13292-46-1 Usage
Inhibitor of Nucleic Acid Synthesis
Rifampicin and other compounds of the ansamycin group specifically inhibit DNA-dependent RNA polymerase; that is, they prevent the transcription of RNA species from the DNA template. Rifampicin is an extremely efficient inhibitor of the bacterial enzyme, but fortunately eukaryotic RNA polymerase is not affected. RNA polymerase consists of a core enzyme made up of four polypeptide subunits, and rifampicin specifically binds to the β subunit where it blocks initiation of RNA synthesis, but is without effect on RNA polymerase elongation complexes. The structural mechanism for inhibition of bacterial RNA polymerase by rifampicin has recently been elucidated. The antibiotic binds to the β subunit in a pocket which directly blocks the path of the elongating RNA chain when it is two to three nucleotides in length. During initiation the transcription complex is particularly unstable and the binding of rifampicin promotes dissociation of short unstable RNA DNA hybrids from the enzyme complex. The binding pocket for rifampicin, which is absent in mammalian RNA polymerases, is some 12 ? away from the active site.
Description
Rifampicin is a semisynthetic derivative of rifamicin B, a macrolactam antibiotic and one
of more than five antibiotics from a mixture of rifamicins A, B, C, D, and E, which is called
a rifamicin complex, which is produced by actinomycetes Streptomyces mediteranei
(Nocardia mediteranei). It was introduced into medical practice in 1968. Synthesis of
rifampicin begins with an aqueous solution of rifamicin, which under the reaction conditions
is oxidized to a new derivative of rifamicin S (32.7.4), with the intermediate formation of rifamicin O (32.7.3). Reducing the quinone structure of this product with hydrogen using a
palladium on carbon catalyst gives rifamicin SV (32.7.5). The resulting product undergoes
aminomethylation by a mixture of formaldehyde and pyrrolidine, giving 3-pyrrolidinomethylrifamicin SV (32.7.6). Oxidizing the resulting product with lead tetracetate to an
enamine and subsequent hydrolysis with an aqueous solution of ascorbic acid gives
3-formylrifamicin SV (32.7.7). Reacting this with 1-amino-4-methylpiperazine gives the
desired rifampicin (32.7.8).
Chemical Properties
Red to Orange Crystalline Solid
Uses
Different sources of media describe the Uses of 13292-46-1 differently. You can refer to the following data:
1. Semisynthetic antibiotic. Antibacerial (tuberculostatic)
2. antibacterial (tuberculostatic)
3. Rifampin is used as an antibiotic. It is a semisynthetic derivative
of rifamycin B, a macrocyclic antibiotic produced by the mold
Streptomyces mediterranei. Rifampin is used for the treatment of
tuberculosis, brucellosis, Staphlococcus aureus, and other infectious
diseases.
4. Rifampicin is used to treat Tuberculosis and Tuberculosis-related mycobacterial infections. It is widely used as an antipruritic agent in the autoimmune cholestatic liver disease, primary biliary cirrhosis (PBC). It has been shown to cause hepatitis.
Indications
Rifampin (300 to 450 mg daily) is very effective in relieving the pruritus of
primary biliary cirrhosis, by inhibiting hepatic bile uptake and stimulating
mixed-function oxidases. Liver enzymes should be monitored to detect druginduced
hepatitis.
Definition
ChEBI: A member of the class of rifamycins that is a a semisynthetic antibiotic derived from Amycolatopsis rifamycinica (previously known as Amycolatopsis mediterranei and Streptomyces mediterranei)
Brand name
Rifadin (Sanofi Aventis); Rimactane (Actavis).
Antimicrobial activity
It exhibits potent activity in vitro against Gram-positive cocci, including methicillin-resistant staphylococci (MIC <0.025–0.5 mg/L) and penicillinresistant pneumococci. Enterococci are less susceptible. Gram-positive bacilli, including Bacillus spp., Clostridium difficile, Corynebacterium spp. and Listeria monocytogenes, are highly susceptible (MIC 0.025–0.5 mg/L). The pathogenic Neisseria and Moraxella spp. are also highly susceptible. Enteric Gram-negative bacteria are generally less sensitive (MIC 1–32 mg/L), but Bacteroides fragilis is highly susceptible. Among other Gram-negative bacilli, Haemophilus influenzae, H. ducreyi, Flavobacterium meningosepticum and Legionella spp. are highly susceptible (MIC <0.025–2 mg/L). Chlamydia trachomatis and Chlamydophila psittaci are inhibited by low concentrations (0.025–0.5 mg/L). Most strains of M. tuberculosis, M. kansasii and M. marinum are inhibited by <0.01–0.1 mg/L, but M. fortuitum and members of the M. avium complex are resistant. M. leprae is highly sensitive. Rifampicin is active against some eukaryotic parasites through inhibition of the prokaryote-like polymerase of kinetoplasts or mitochondria. Maturation of Plasmodium falciparum is inhibited by 2–10 mg/L; at higher concentrations Leishmania spp. are also inhibited. High concentrations inhibit growth of a variety of poxviruses by interference with viral particle maturation; viral reverse transcriptase is unaffected.
Acquired resistance
Most large bacterial populations contain resistant mutants, which readily emerge in the presence of the drug and can emerge during treatment. The mutation rate to resistance in Staph. aureus, Str. pyogenes, Str. pneumoniae, Esch. coli and Proteus mirabilis is about 10–7 and that to M. tuberculosis and M. marinum 10–9–10–10. Primary resistance in M. tuberculosis remained low for many years, but is increasing. Resistance is of the one-step type, and several classes of mutants exhibiting different degrees of resistance can be selected by exposing a large population to a relatively low concentration of the drug. Some of these mutants may be susceptible to other rifamycin derivatives. Resistance is due to a change in a single amino acid of the β subunit of DNA-dependent RNA polymerase, which no longer forms a stable complex with rifampicin. It is not transferable and there is no cross-resistance with any other antibiotic class. The susceptible strains of the gastrointestinal flora become rapidly resistant during rifampicin treatment without alteration in the flora composition, and revert to susceptibility within a few weeks of cessation of treatment.
General Description
Eppendorf Tubes are the perfect option for working with medium-sized sample volumes!Maximum safety and stability for centrifugation up to 25,000 × gConical bottomsEasier processing of samples up to 5.0 mLHigher yields in DNA isolation, prep of mastermixes and buffers, and safe cell and tissue lysisTransparent polypropylene, free of plasticizers, biocides or mold release agentsHinged lid for minimized sample evaporation during storage and incubation in a wide range of temperatures from -86°C to 80°C
Pharmaceutical Applications
Rifampin (USAN). Molecular weight: 822.95.A semisynthetic derivative of rifamycin SV, available for oral administration or intravenous infusion and in several combined formulations with other antimycobacterial drugs. It is poorly soluble in water, but soluble in organic solvents.
Biochem/physiol Actions
Rifampicin inhibits the assembly of DNA and protein into mature virus particles. It inhibits initiation of RNA synthesis by binding to β-subunit of RNA polymerase, which results in cell death.
Mechanism of action
Rifampin is a semisynthetic macrocyclic antibiotic produced
from Streptomyces mediterranei. It is a large lipidsoluble
molecule that is bactericidal for both intracellular
and extracellular microorganisms. Rifampin binds
strongly to the β-subunit of bacterial DNA-dependent
RNA polymerase and thereby inhibits RNA synthesis.
Rifampin does not affect mammalian polymerases.
Pharmacology
Rifampin is well absorbed orally, and a peak serum concentration
is usually seen within 2 to 4 hours. Drug absorption is impaired if rifampin is given concurrently
with aminosalicylic acid or is taken immediately after a
meal. It is widely distributed throughout the body, and
therapeutic levels are achieved in all body fluids, including
cerebrospinal fluid. Rifampin is capable of inducing
its own metabolism, so its half-life can be reduced
to 2 hours within a week of continued therapy.
The deacetylated form of rifampin is active and undergoes
biliary excretion and enterohepatic recirculation.
Most of the drug is excreted into the GI tract and a
small amount in the urine.Moderate dose adjustment is
required in patients with underlying liver disease.
Pharmacokinetics
Oral absorption：>90% Cmax300 mg oral ：4 mg/L after 2 h 600 mg oral：10 mg/L after 2 hPlasma half-life：2.5 h Volume of distribution：1.5 L/kg Plasma protein binding：80%absorption Rifampicin is virtually completely absorbed when administered orally, but substantial differences in blood levels have been reported in comparisons of capsules or tablets from different manufacturers. Peak plasma levels differ noticeably between individuals. Food affects absorption, the peak plasma levels being delayed and about 2 mg/L lower after a meal. Although the AUC and the length of time for which effective antibacterial levels are maintained are little affected, it is preferable that patients take the drug before meals. Intravenous administration produces AUCs and elimination half-lives similar to those obtained after oral doses.DistributionThe lipid solubility of the drug facilitates its distribution. It is widely distributed in the internal organs, bones and fluids, including tears, saliva, ascitic fluid and abscesses. It penetrates into cells and is active against intracellular bacteria. Low concentrations are found in the cerebrospinal fluid (CSF), but these are substantially higher when the meninges are inflamed. Concentrations around 60% of the simultaneous plasma value were found in the heart valves of patients receiving a 600 mg dose before surgery.MetabolismRifampicin is metabolized principally to its desacetyl derivative, which is also antimicrobially active, and this process is accelerated by its stimulatory effect on hepatic microsomal enzymes. As a consequence, hepatic clearance increases on continuous administration and, especially with high doses, the serum half-life becomes shorter after a few days of treatment.excretionThe main route of elimination is secretion into the bile, a process that is dose dependent, being efficient at low dosage but limited at high dosage. As a result, the dose determines the proportion excreted via the bile or passing the liver to be excreted in the urine. Because there is a limit to the rate at which the liver can deliver the drug to the bile, the elimination half-life after a 600 mg dose rises to 3 h and may be as long as 5 h with a 900 mg dose. The desacetyl compound is mainly found in the bile, where the parent compound accounts for only 15% of the total. Plasma levels are increased by hepatic insufficiency and biliary obstruction, and by probenecid, which depresses hepatic uptake. The drug escaping biliary excretion appears in the urine, to which it imparts an orange–red color, the parent compound and the desacetyl metabolites being present in about equal proportions. The plasma concentration and half-life are not significantly affected by renal failure. The drug is not removed by hemodialysis.
Clinical Use
Different sources of media describe the Clinical Use of 13292-46-1 differently. You can refer to the following data:
1. The incidence of hepatotoxicity was significantly higher when rifampin was combined with isoniazid than when either agent was combined with ethambutol. Allergic and sensitivity reactions to rifampin have been reported, but they are infrequent and usually not serious. Rifampin is a powerful inducer of hepatic cytochrome P450 oxygenases. It can markedly potentiate the actions of drugs that are inactivated by these enzymes. Examples include oral anticoagulants, barbiturates, benzodiazepines, oral hypoglycemic agents, phenytoin, and theophylline. Rifampin is also used to eradicate the carrier state in asymptomatic carriers of Neisseria meningitidis to prevent outbreaks of meningitis in high-risk areas such as military facilities. Serotyping and sensitivity tests should be performed before its use because resistance develops rapidly. However, a daily dose of 600 mg of rifampin for 4 days suffices to eradicate sensitive strains of N. meningitidis. Rifampin has also been very effective against M. leprae in experimental animals and in humans. When it is used in the treatment of leprosy, rifampin should be combined with dapsone or some other leprostatic agent to minimize the emergence of resistant strains of M. leprae. Other, nonlabeled uses of rifampin include the treatment of serious infections such as endocarditis and osteomyelitis caused by methicillin-resistant S. aureus or S. epidermidis, Legionnaires disease when resistant to erythromycin, and prophylaxis of H. influenzae induced meningitis. Rifampin occurs as an orange to reddish brown crystalline powder that is soluble in alcohol but only sparingly soluble in water. It is unstable to moisture, and a desiccant (silica gel) should be included with rifampin capsule containers. The expiration date for capsules stored in this way is 2 years.
2. Tuberculosis (in combination with other antituberculosis agents; see Ch. 58) Leprosy (in combination with other antileprotic agents; see Ch. 57) Serious infection with multiresistant staphylococci and pneumococci (in combination with a glycopeptide) Elimination of nasopharyngeal carriage of Neisseria meningitidis and H. influenzae.
3. Rifampin is a first-line antitubercular drug used in the
treatment of all forms of pulmonary and extrapulmonary
tuberculosis. Rifampin is an alternative to isoniazid
in the treatment of latent tuberculosis infection.
Rifampin also may be combined with an antileprosy
agent for the treatment of leprosy and to protect those
in close contact with patients having H. influenza type b
and N. meningitidis infection; rifampin is also used in
methicillin-resistant staphylococcal infections, such as
osteomyelitis and prosthetic valve endocarditis.
Side effects
Different sources of media describe the Side effects of 13292-46-1 differently. You can refer to the following data:
1. The most commonly observed side effects are GI disturbances
and nervous system symptoms, such as nausea,
vomiting, headache, dizziness, and fatigue.Hepatitis
is a major adverse effect, and the risk is highest in patients
with underlying liver diseases and in slow isoniazid
acetylators; the rate of hepatotoxicity is increased
if isoniazid and rifampin are combined.
Other major untoward reactions are the result of rifampin’s
ability to induce hepatic cytochrome P-450 enzymes,
leading to an increased metabolism of many
drugs; this action has especially complicated the treatment
of tuberculosis in HIV-infected patients whose regimen
includes protease inhibitors and nonnucleoside reverse
transcriptase. Since rifabutin has relatively little of
these effects, it is commonly substituted for rifampin in
the treatment of tuberculosis in HIV-infected patients.
Hypersensitivity reactions, such as pruritus, cutaneous
vasculitis, and thrombocytopenia, are seen in some
patients, and an immune-mediated systemic flulike syndrome
with thrombocytopenia also has been described.
Rifampin imparts a harmless red-orange color to urine,
feces, saliva, sweat, tears, and contact lenses. Patients
should be advised of such discoloration of body fluids.
2. Rifampicin is relatively non-toxic, even when administered for a long period (as in the treatment of tuberculosis). However, several unwanted effects, including pink staining of soft contact lenses, are associated with its use. Other reactions can be divided into those associated with daily or intermittent administration, and those found only with intermittent therapy.
Safety Profile
Suspected carcinogen with experimental neoplastigenic and teratogenic data. Poison by intraperitoneal and intravenous routes. Moderately toxic to humans by ingestion. Moderately experimentally toxic by ingestion and subcutaneous routes. Human systemic effects by ingestion: conjunctiva irritation, iritis (inflammation of the iris), other eye effects, dermatitis. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits toxic fumes of NOx.
Drug interactions
Potentially hazardous interactions with other drugs
Anthelmintics: concentration of praziquantel
reduced - avoid.
Anti-arrhythmics: metabolism of disopyramide,
and propafenone accelerated; concentration of
dronedarone reduced - avoid.
Antibacterials: reduced concentration of bedaquiline,
chloramphenicol, delamanid, clarithromycin,
dapsone, doxycycline, linezolid and trimethoprim
and possibly tinidazole - avoid with bedaquiline;
concentration increased by clarithromycin and other
macrolides; increased risk of hepatotoxicity with
isoniazid.
Anticoagulants: reduced anticoagulant effect of
coumarins; reduced concentration of apixaban,
edoxaban and rivaroxaban; avoid with dabigatran.
Antidepressants: concentration of vortioxetine
reduced - consider increasing vortioxetine dose.
Antidiabetics: reduced antidiabetic effect of
linagliptin and tolbutamide; concentration
of canagliflozin, nateglinide and repaglinide
reduced; possibly reduced antidiabetic effect with
sulphonylureas.
Antiepileptics: reduced concentration of
brivaracetam, fosphenytoin, phenytoin and
lamotrigine; concentration possibly reduced by
phenobarbital.
Antifungals: concentration of both drugs may be
reduced with ketoconazole; reduced concentration
of fluconazole, itraconazole, posaconazole and
terbinafine - avoid with itraconazole; concentration
of isavuconazole and voriconazole reduced -
avoid; initially increases then reduces caspofungin
concentration.
Antimalarials: avoid with piperaquine with
artenimol; concentration of mefloquine reduced -
avoid, concentration of quinine reduced.
Antimuscarinics: concentration of active metabolite
of fesoterodine reduced - avoid.
Antipsychotics: reduced concentration of
haloperidol, aripiprazole and clozapine - increase
dose of aripiprazole; concentration of lurasidone
reduced - avoid.
Antivirals: concentration of abacavir, dasabuvir,
ombitasvir, paritaprevir, ritonavir and tipranavir
possibly reduced - avoid with dasabuvir, ombitasvir,
paritaprevir and tipranavir; concentration of
atazanavir, boceprevir, daclatasvir, darunavir,
etravirine, fosamprenavir, indinavir, lopinavir,
nevirapine, ombitasvir, rilpivirine, saquinavir,simeprevir and telaprevir reduced also risk of
hepatotoxicity with saquinavir - avoid; concentration
of efavirenz, maraviroc and raltegravir reduced -
increase dose of efavirenz and possibly maraviroc
and raltegravir; avoid with elvitegravir, ledipasvir,
sofosbuvir and zidovudine; concentration of
dolutegravir reduced.
Apremilast: concentration of apremilast reduced -
avoid.
Atovaquone: concentration of atovaquone reduced
(possible therapeutic failure of atovaquone);
concentration of rifampicin increased - avoid.
Bosentan: reduced bosentan concentration - avoid.
Calcium-channel blockers: metabolism of diltiazem,
verapamil, isradipine, nicardipine, nifedipine and
nimodipine accelerated.
Cannabis extract: concentration of cannabis extract
reduced - avoid.
Ciclosporin: markedly reduced levels (danger of
transplant rejection); ciclosporin dose may need
increasing 5-fold or more.
Cobicistat: concentration of cobicistat possibly
reduced - adjust cobicistat dose.
Corticosteroids: reduced level of corticosteroids -
double steroid dose. Give as twice daily dosage.
Cytotoxics: reduced concentration of axitinib,
brentuximab, bortezomib, bosutinib, cabazitaxel,
cabozantinib, ceritinib, crizotinib, dabrafenib,
dasatinib, everolimus, gefitinib, ibrutinib, idelalisib,
imatinib, lapatinib, nilotinib, nintedanib, olaparib,
osimertinib, panobinostat, ponatinib, regorafenib,
vandetanib, vemurafenib, vinflunine and vismodegib
- avoid; concentration of afatinib, erlotinib,
ruxolitinib, sorafenib, sunitinib and trabectedin
and possibly eribulin and pazopanib reduced;
concentration of everolimus reduced - avoid or
increase everolimus dose; active metabolite of
temsirolimus reduced - avoid.
Diuretics: concentration of eplerenone reduced -
avoid.
Guanfacine: concentration of guanfacine reduced -
increase dose of guanfacine.
Hormone antagonists: concentration of abiraterone
reduced - avoid; concentration of tamoxifen and
possibly exemestane reduced.
Ivacaftor: concentration of ivacaftor reduced - avoid.
Macitentan: concentration of macitentan reduced -
avoid.
Mycophenolate: concentration of active
mycophenolate metabolite reduced.
Naloxegol: concentration of naloxegol reduced -
avoid.
Netupitant: concentration of netupitant reduced -
avoid.
Oestrogens and progestogens: reduced contraceptive
effect due to increased metabolism.
Ranolazine: concentration of ranolazine reduced -
avoid.
Roflumilast: effects of roflumilast inhibited - avoid.
Sirolimus: reduced sirolimus concentration.
Tacrolimus: reduced tacrolimus concentration.
Tadalafil: concentration of tadalafil reduced - avoid.
Ticagrelor: concentration of ticagrelor reduced.
Ulipristal: contraceptive effect possibly reduced -
avoid.
Environmental Fate
Physicochemical Properties
Rifampicin or rifampin is a red to orange odorless powder. It is
very slightly soluble in water (1 g per 762 ml at pH <6),
acetone, carbon tetrachloride, ethanol, and ether; freely soluble
in chloroform and dimethyl sulfoxide (DMSO); soluble in
ethyl acetate and methanol and tetrahydrofuran. The solubility of rifampin increases at acidic pH. Rifampin has a melting
point of 138–188 °C and a pKa of 1.7 related to the 4-OH
moiety and 7.9 related to the 3-piperazine nitrogen moiety.
In 1% suspension in water, the pH is 4.5–6.5.
Exposure Pathway
Ingestion is the most common route of exposure. Rifampin is
available in oral and parenteral forms.
Toxicokinetics
Rifampin is rapidly and nearly completely absorbed from the
gastrointestinal tract. Peak serum levels are seen within
2–4 h. Food, antacids, ketoconazole, and aminosalicylic acid
interfere with absorption and delay peak levels. If these
agents are used concurrently, they should be administered
separately at an interval of at least 8 h. Massive ingestions in
the overdose setting may also delay absorption. Protein
binding is 75–90%. The volume of distribution is approximately
1 l kg-1. Rifampin undergoes hepatic deacetylation to
an active metabolite. Both rifampin and its deacetylated
metabolite are excreted into the bile. Rifampin and to a lesser
extent its deacetylated metabolite undergo enterohepatic
recirculation. The half-life of therapeutic doses of rifampin is
1.5–5 h. The half-life is shortened after regular use due to
induction of hepatic enzymes. Chronic liver disease increases
the half-life. The kinetics are not well described in the
overdose setting.
Metabolism
Rifampicin is rapidly metabolised in the liver mainly
to active 25-O-deacetylrifampicin and excreted in the
bile. Deacetylation diminishes intestinal reabsorption
and increases faecal excretion, although significant
enterohepatic circulation still takes place. About 60%
of a dose eventually appears in the faeces. The amount
excreted in the urine increases with increasing doses
and up to 30% of a dose may be excreted in the urine,
about half of it being unchanged drug. The metabolite
formylrifampicin is also excreted in the urine.
Purification Methods
This macrolide antibiotic crystallises form Me2CO in red-orange plates. It has UV max at 237, 255, 334, and 475nm ( 33,200, 32,100, 27,000 and 15,400) at pH 7.38. It is stable in Me2SO and H2O and is freely soluble in most organic solvents but slightly soluble in H2O at pH <6. [Binda et al. Arzneim.-Forsch 21 1907 1971.] It inhibits cellular RNA synthesis without affecting DNA [Calvori et al. Nature 207 417 1965].
Toxicity evaluation
In the acute overdose setting, the mechanism of toxicity is not
defined. A number of toxic reactions occurring with intermittent
dosing schedules or on reexposure are postulated to be due
to the presence of antirifampin antibodies.
Check Digit Verification of cas no
The CAS Registry Mumber 13292-46-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,3,2,9 and 2 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 13292-46:
(7*1)+(6*3)+(5*2)+(4*9)+(3*2)+(2*4)+(1*6)=91
91 % 10 = 1
So 13292-46-1 is a valid CAS Registry Number.
InChI:InChI=1/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14+,22-13-,44-20?/t21?,23-,24-,25-,29+,34+,35-,39+,43+/m1/s1
13292-46-1Relevant articles and documents
Antitubercular nanocarrier combination therapy: Formulation strategies and in vitro efficacy for rifampicin and SQ641
Daddio, Suzanne M.,Reddy, Venkata M.,Liu, Ying,Sinko, Patrick J.,Einck, Leo,Prudhomme, Robert K.
, p. 1554 - 1563 (2015)
Tuberculosis (TB) remains a major global health concern, and new therapies are needed to overcome the problems associated with dosing frequency, patient compliance, and drug resistance. To reduce side effects associated with systemic drug distribution and
Process method for synthesizing rifampicin
-
Paragraph 0059; 0063-0065; 0069-0071; 0075-0077; 0081-0082, (2020/11/24)
The invention relates to a process method for synthesizing rifampicin, wherein the process method mainly comprises the steps: by using rifamycin S as a raw material, carrying out cyclization reactionto obtain a rifamycin oxazine-containing solution, and carrying out solventing-out crystallization on the rifamycin oxazine-containing solution to obtain a rifamycin oxazine crude product; carrying out condensation reaction on the crude rifamycin oxazine product and 1-amino-4-methylpiperazine to obtain a reaction solution containing rifampicin; and cooling and crystallizing the reaction solution containing rifampicin to obtain a rifampicin product. Compared with the prior art, the method has the advantages that the reaction steps are few, the product yield is high, the reaction raw material cost is low, meanwhile, the production is more environmentally friendly, the consumption of raw materials is reduced by 30% (the consumption of dimethylol tert-butylamine required by every 1 kg of rifamycin S is reduced by about 28%, and the consumption of 1-amino-4-methylpiperazine is reduced by about 30%). The method overcomes the defect that a large amount of sewage is generated in production byadopting an elution method, and reduces the influence of impure reaction products on the yield due to the fact that rifamycin S-Na is used as a raw material.
Method for preparing rifampicin through micro-channel reaction device
-
Paragraph 0037-0056, (2018/09/29)
The invention discloses a method for preparing rifampicin through a micro-channel reaction device. Through the micro-channel reaction device, rifamycin S serves as the raw material, and a coarse rifampicin product is directly obtained through the cyclization, hydrolysis, condensation and crystallization process without the after-treatment process. The complete continuity of production of the rifampicin is realized, and the rifampicin is high in yield, low in cost, high in benefit, environmentally friendly, capable of saving energy, high in efficiency and suitable for industrial application.
Method for preparing rifampicin by utilizing cascade reaction of kettle type reaction device and microchannel reaction device
-
Paragraph 0033; 0034; 0043; 0044; 0051-0062; 0065-0068, (2017/08/28)
The invention provides a method for preparing rifampicin by utilizing cascade reaction of a kettle type reaction device and a microchannel reaction device. In the kettle type reaction device, rifamycin S sodium salt is used as a raw material to obtain N-tedin-1,3-oxazine (5,6-C) rifamycin through reaction, and the N-tedin-1,3-oxazine (5,6-C) rifamycin reacts with 1-methyl-4-amino-piperazine in the microchannel reaction device to obtain the rifampicin. Continuous production of the rifampin is achieved, the product quality is good, the cost is low, the profit is high, and the method is green, environmentally friendly, capable of saving energy, efficient and suitable for industrial application.
