Happy Chinese New Year ! ! !
At the beginning of the new year, everything is renewed, on the occasion of this new year, we sincerely thank our customers for their support and co-operation with us in the past year. In the new year, our company will work harder to provide you with better service, our Spring Festival holiday arrangements are as follows: from 9th February 2024 to 18th February 2024. We hope you could understand the inconvenience caused by the holiday. We will arrange a special person to reply the message and make the projects run normally. We wish you all a happy Chinese New Year and a happy family!
Ticagrelor: the World’s First Reversible Combination Orally-administered P2Y12 Adenosine Diphosphate Receptor Antagonist
Ticagrelor, a new platelet aggregation inhibitor, is the world’s first reversible combination orally-administered P2Y12 adenosine diphosphate receptor antagonist. It is used to reduce cardiovascular death and heart attacks in patients with acute coronary syndrome. Ticagrelor is white to off-white powder with hygroscopic, so low temperature storage and transport is required. Mechanism Ticagrelor has reversibly acts on the 2 purine receptor subtype P2Y12, of vascular smooth muscle cells (VSMC,) which does not require metabolic activation, and has a significant inhibitory effect on platelet aggregation induced by adenosine diphosphate. In this case, platelet function will recover rapidly after stopping the dose. Features Rapid onset of action Ticagrelor can be absorbed in approximately 1.5 hours and After about 2.5 hours, ticagrelor can rapidly transformed into circulating metabolite AR-C124910XX. The mean bioavailability of ticagrelor was approximately 36%. Powerful drug Without increasing major bleeding, ticagrelor treatment for 12 months significantly reduced the risk of cardiovascular death by 21% compared with clopidogrel. Ticagrelor is already a first recommended drug for cardiovascular disease in Europe. Platelet function recovered quickly The interaction between ticagrelor and platelet P2Y12 ADP receptor is reversible, without conformational change and signal transmission, and platelet function in blood recovers rapidly after drug withdrawal. Sythesis Ticagrelor is mainly composed of three major fragments: a five-membered ring, a thioether pyrimidine, and a three-membered ring. At present, a variety of synthesis routes have been reported, and the common point is that there is no construction of chiral centers in the synthesis process, and all the six chiral centers are introduced by starting materials. In this synthetic route, starting materials S1 and S2 were coupled, then the ring was diazosed off under the conditions of sodium nitrite and acetic acid, and then coupled with starting material S3. Finally, the finished product of ticagrelor was obtained by removing the forkone protection. Usage and dosage Oral administration. This product can be taken before or after meals. The initial dose was a single dose of 180 mg, followed by 90 mg twice a day. It should be used in combination with aspirin unless clearly contraindicated. After the initial loading dose of aspirin, aspirin was maintained at a dose of 75 to 100mg once daily. Ticagrelor can be started in ACS patients who have already received a loading dose of clopidogrel. Treatment may be given for up to 12 months unless there is a clinical indication to discontinue treatment. Cautions The most frequently reported adverse effects were dyspnea, contusion, and epistaxis in patients who received ticagrelor, which occurred more frequently than in patients who received clopidogrel. Among patients with acute coronary syndromes who are treated with ticagrelor combined with aspirin, there is an increased risk of bleeding. Therefore, the increase of bleeding risk should be balanced against the benefit of preventing atherothrombotic events. Interruptions of ticagrelor tablets should be avoided. If ticagrelor must be temporarily discontinued, treatment should be restarted as soon. The risks of myocardial infarction, thrombosis, even death would increase if ticagrelor is discontinued.
Fosfomycin Tromethamine, a Broad-Spectrum Bactericidal, Especially for Lower Urinary Tract Infections.
Fosfomycin is a broad-spectrum bactericidal for human and animals purposes, which inhibits the growth of E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc.. Fosfomycin tromethamine is a phosphonic acidepoxide derivative, which expands the therapeutic utility of fosfomycin salt because its water solubility increased enough to allow oral administration. This compound is a white to off-white powder with great hygroscopic and solubility in water. Mechanism Fosfomycin tromethamine, is a derivate of fosfomycin, which was initially isolated from fermentationsof streptomyces spp and been used as human medicine and veterinary medicine for over 50 years. Fosfomycin can inactivate the first enzyme in the bacterial cell wall biosynthesis pathway, which occurs through nucleophilic opening of the epoxide ring. Fosfomycin tromethamine only acts on the bacterial cell wall, human cells do not have this target site and is not affected. In this case this compound can be used in pregnant women, children and elderly patients. Features Broad spectrum antibiotic Fosfomycin sodium is a broad-spectrum antibiotic of Gram-positive and Gram-negative bacteria, for instance E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc. and is particularly suitable for the treatment of acute cystitis Rapid sterilization After oral administration, fosfomycin tromethamine is rapidly decomposed into fosfomycin and tromethamine in the body. With the characteristics of low molecular weight and high hydrophilicity, fosfomycin tromethamine appears good distribution in fluid and strong penetration. So this medicine can widely distribute in body fluid and tissue to increase curative effect. Tromethamine is a weakly osmotic diuretic, which can alkalinize urine and effectively reduces the symptom of urinary tract irritation. Low toxicityand residue of Fosfomycin tromethamine Bioavailability of Fosfomycin tromethamine by oral administration is from 34% to 41% in healthy adults, 37% in fasting and 30% after eating. It shows little irritation on the body, no acute toxicity and adverse reactions. The maximum plasma concentration was reached within 2 to 2.5 hours after dose, and will be excreted mainly in its original form in urine and feces in 48h. Sythesis The synthesis of fosfomycin tromethamine use fosfomycin sodium as an intermediate. Prepare a certain concentration tromethamine-sulfuric acid solution and then it was added to fosfomycin sodium aqueous solution by drop. After that the sodium sulfate solid is precipitated with methanol and the filtrate is crystallized at low temperature with n-butanol to obtain fosfomycin tromethamine. Fosfomycin Tromethamine Clinical Application Fosfomycin tromethamine is used for the treatment of acute uncomplicated lower urinary tract infections caused by sensitive bacteria (such as acute cystitis, acute onset of chronic cystitis, acute urethrovesical syndrome, non-specific urethritis, asymptomatic bacteriuria during pregnancy, and urinary tract infections after surgery) and for the prevention of urinary tract infections during surgery and infections caused by diagnostic procedures of the urinary tract. Usage and dosage Adults: single-dose treatment, 3g active ingredient per course; Clinical symptoms usually resolve 2 to 3 days after treatment. For preventing infections caused by surgical procedures and urinary tract care: 6g active ingredient per dose, with first dose taken 3 hours before surgery and second dose taken 24 hours after surgery. Cautions The main symptoms of fosfomycin tromethamine were are diarrhea and soft stools, occasional rash and nausea, which will disappear after drug withdrawal. It is not known whether fosfomycin tromethamine is excreted in human milk, but given the potential for serious adverse effects of fosmycin tromethamine in lactating infants, it should not be administered to lactating women. The efficacy and safety of fosfomycin tromethamine in children aged 12 years and younger are lack of sufficient and well-designed clinical verification.
Baloxavir Marboxil a New Drug against Influenza with Noval Mechanism
Baloxavir Marboxil is a new anti-influenza drug developed by Shionogi Pharmaceutical from Japan and Roche from Switzerland. The drug was first approved for use in Japan in February 2018 and later by the FDA in October for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours. Baloxavir marboxil is a cap-endonuclease inhibitor, which has a unique mechanism of action to Inhibit the proliferation of influenza virus. Mechanism Baloxavir marboxil is a prodrug that enters the body and is hydrolyzed to the active substance baloxavir, which plays an anti-influenza virus activity. Baloxavir is a selective inhibitor of influenza cap-endonuclease, an enzyme required for viral gene transcription and replication, which prevents polymerase function and influenza virus mRNA replication. It has therapeutic activity against both influenza A and B virus infections, even strains resistant to current antiviral drugs. Baloxavir marboxil inhibits an enzyme of viral replication, thus the flu virus infection can be rapidly treated and the symptoms will be alleviated. Features New antiviral influenza drug Baloxavir marboxil is the first anti-influenza virus drug with a new mechanism in the past 20 years. Cpmpared with traditional anti-influenza drugs, Baloxavir Marboxil selectively inhibits the CAP-endonuclease of influenza virus, thereby preventing polymerase function and influenza virus mRNA replication.This unique mechanism gives Baloxavir Marboxil a unique advantage against influenza viruses. Excellent activity of anti influenzavirus Baloxavir marboxil has excellent anti-virus performance against influenza, including influenza A virus (IAV) and influenza B virus (IBV). A single dose of Baloxavir marboxil was shown to be superior to placebo in relieving influenza symptoms and superior to both oseltamivir and placebo drug in virologic outcomes (marked by decreased viral load). Highly effective and long acting drug Baloxavir marboxil is a prodrug. By oral administration, almost all baloxavir marboxil is converted to the active constituent baloxavir. The tmax of Baloxavir to reach the Cmax in vivo is about 4 hours on average. The average half-life of bacalovirda in vivo is approximately 80 hours, so only one dose is needed for most patients. These make Baloxavir marboxil a highly effective and long acting drug. Synthesis The synthesis of Baloxavir marboxil mainly divided into two parts. In each part, a main intermediate is synthesized separately. In the synthesis of intermediate A (1985607-83-7), 7-(Benzyloxy)-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione (intermediate A-2, 1370250-39-7) yields the intermediate A by cyclization and reduction reactions. The coupling of the intermediate A and intermediate B was carried out under dehydration conditions of 1-propanephosphonic anhydride (T3P) and methanesulfonic acid at 70℃ to obtain protected Baloxavir N-2. Compound N-2 was then reacted with 0.6 equivalents of PhBr and K2CO3. Debenzylation was then carried out using LiCl in CH3CONMe2 to give Baloxavir acid in 94% yield. In the final step, Baloxavir acid was reacted with chloromethyl methyl carbonate in dimethylacetamide in 93% yield to form Baloxavir marboxyl. Usage and dosage The Baloxavir Marboxil is used for the treatment of acute uncomplicated influenza in patients (adults and pediatric patients 5 years of age and older) who have been symptomatic for no more than 48 hours. Baloxavir marboxil should be taken as a single dose as soon as possible and within 48 hours of influenza symptom onset for treatment of acute uncomplicated influenza. The specific dose should be adjusted according to the patient’s weight as follow: 20 kg to less than 80 kg: 40mg At least 80 kg: 80mg Cautions Hypersensitivity such as anaphylaxis, angioedema, urticaria, and erythema multiforme may occur or be suspected. Increased incidence of treatment-emergent resistance in patients less than 5 years of age. Baloxavir Marboxil has not been shown to prevent serious bacterial infections, which may begin with influenza-like symptoms or may coexist with, or occur as, a complication of influenza.
Merry Christmas and a prosperous New Year!
Merry Christmas and a prosperous New Year!
Semaglutide Starts the New Life with Type 2 Diabetes
Semaglutide, brand names as Ozempic, Wegovy, and Rybelsus, is an anti-diabetic drug developed by Novo Nordisk, which is used to treat type 2 diabetes and manage chronic weight. With good hydrophilicity, low renal excretion, long half-life in the body, It has great ability to control blood glucose level with great convenience by injection once a week. Semaglutide is white or pale-yellow lyophilized powder, so low temperature storage and transport is required. Mechanism Semaglutide is a glucagon-like peptide-1(GLP-1) receptor agonist with 94% sequence homology with human GLP-1. It increases the production of insulin, which can lower the blood glucose level. Semaglutide also appears to enhance growth of β cells, sites of insulin production, in the pancreas. By lowering appetite and slowing down digestion in the stomach, Semaglutide also can reduce food intake to control body weight. Features Safe and stable blood glucoselevel control Semaglutide has a blood glucose concentration-dependent effect, which can increase pancreas responsiveness to glucose and inhibit the glucagon secretion. When blood glucose is lowered, this effect is diminished synchronously. So the risk of hypoglycemia will be lowered. User-friendly Maximum concentrations of Semaglutide were reached 1-3 days after administration. Steady-state exposure was reached after 4 to 5 weeks of once-weekly dosing. Compared with native GLP-1, Semaglutide has a longer half-life, approximately 1 week. Patients with type 2 diabetes can achieve good blood glucose control with only one injection per week. Cardiovascular and renal protection effects Multiple studies have shown that Semaglutide can significantly reduce the risk of adverse cardiovascular events and stroke. Semaglutide is also reported to reduce the proteinuria, uric acid, glomerular sclerosis. Manage chronic weight Semaglutide also can reduce food intake to control body weight, by lowering appetite and slowing down digestion in the stomach. FDA approved usage of Semaglutide for long-term weight control. Sythesis The synthesis of Semaglutide mainly contains two methods, fermentation and chemical synthesis. In fermentation method, several bacterial strains are chosen to product Semaglutide precursor. After the precursor is purified, further reaction undergoes to obtain Semaglutide. In chemical synthesis, Semaglutide’s long peptide chain is divided into four parts, intermediate 1, 2, 3 and 4. Each intermediate is synthesized separately, and finally synthesizes to Semaglutide. Additionally, intermediate 1 has a side chain, which should be synthesized previously. Semaglutide side chain Semaglutide intermediate 1 Semaglutide intermediate 2 Semaglutide intermediate 3 Semaglutide int 4 Usage and dosage The starting dose of Semaglutide was 0.25mg once weekly. After 4 weeks, dose should be increased to 0.5mg once weekly and adhere for at least 4 weeks. Whereafter, dose may be increased to 1 mg once a week, in order to further improve blood sugar control level. Weekly dose of more than 1mg is not recommended. Cautions Reported adverse effects in clinical trials of Semaglutide were gastrointestinal disorders, including nausea (very common), diarrhea (very common), and vomiting (common). Usually, these adverse effects are mild and duration is short. Semaglutide should not be used in patients with type 1 diabetes or in the treatment of diabetic ketoacidosis. This product is not a substitute for insulin. Semaglutide is not recommended for patients with grade IV congestive cardiac failure.
Fosfomycin sodium, a broad-spectrum antibiotic of Gram-positive and Gram-negative bacteria with excellent curative effect
Fosfomycin sodium is a compound with the appearance of white or off-white powder at room temperature, hygroscopic, freely soluble in water or aqueous solution. Mechanism Fosfomycin Sodium, is a derivate of fosfomycin, a type of macrolide antibiotics, which was first isolated from Streptomyces fradicle in 1960s and has been used as human medicine and veterinary medicine for over 50 years. Fosfomycin Sodium is a competitive inhibitor of a bacterial cell wall synthesis enzyme, inhibiting the first synthesis reaction of the bacterial cell wall by hindering the utilization of related substances. Features · Broad spectrum antibiotic Fosfomycin sodium is a broad-spectrum antibiotic of Gram-positive and Gram-negative bacteria, for instance E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc. and is wildly used in the treatment of infection of respiratory, urinary, intestinal, genital systems etc.. · Rapid sterilization With the characteristics of low molecular weight and high hydrophilicity Fosfomycin Sodium appears good distribution in fluid and strong penetration. So this medicine can widely distribute in body fluid and tissue to increase curative effect. About 25% of the E. coli were killed at 1 hour after exposured to Fosfomycin Sodium (12.5μg/ml), and all died within 4-6 hours. Pseudomonas aeruginosa and Staphylococcus aureus were also all killed at 4 and 8 hours. · Low toxicity and residue Fosfomycin Sodium shows little irritation on the body, no acute toxicity and adverse reactions. Single dose will be eliminated by kidney in 18-72 hours for muscles and organs to reach the residual standard with no increasing burden on the kidney. · Extensive usage Fosfomycin Sodium is wildly used for human and livestock in all countries with no restriction in regulation. Sythesis The Synthesis of Fosfomycin Sodium starts from fosfomycin phenylethylamine. Basic fosfomycin sodium (PH 9.0-10.5) was obtained through the reaction between fosfomycin phenylethylamine with NaOH or MeONa. Basic crude production recrystallizes in acetone to obtain neutral fosfomycin phenylethylamine. Clinical Application Fosfomycin Sodium is wildly use for the treatment of infections caused by Staphylococcus aureus, Escherichia coli, Proteus and Shigella etc.. It is usually used to treat uncomplicated urinary tract infections and to reduce nephrotoxicity and ototoxicity of platinum-containing anti-tumor agents. It is also used for susceptibility studies of Klebsiella pneumoniae and to study in vitro susceptibility testing procedures for fosfomycin tromethamine. Usage and dosage · Fosfomycin Sodium For Human I.v.drip: dissolve in sterilized water, then dilute it into 250-500ml 5% glucose injection or sodium chloride injection for intravenous infusion. Adult: 4-12g/day in 2-3 times; Child: 0.1-0.3 per kg/day in 2-3 times. · Fosfomycin Sodium On Veterinary Drinking water：5-10g/100kg in water, twice daily for 3 days; Mixed feed: 10-15g/100kg in feed, twice daily for 3 days. Combination therapy Intestinal infections: combine with β-lactam, aminoglycoside; Respiratory and lung infections: combine with macrolides, β-lactam; Staph infections: combine with erythromycin, rifampin; Acute respiratory infections, sepsis, peritonitis etc.: increase the dose and combine with β-lactams or aminoglycosides. Cautions It may cause mild gastrointestinal reaction as Fosfomycin Sodium‘s Side Effects, for instance nausea, anorexia, epigastric discomfort, loose stools or mild diarrhea, which generally does not affect the continuous dosing. Phlebitis is occasionally reported at high dose and rapid drip in i.v.drip, so the speed of drip should be in control. Liver function should be monitored in large-dose therapy. When use as veterinary medicine, Fosfomycin Sodium used for pigs, chickens and fish mainly; therapy for other animals should be under veterinary guidance.
Happy Chinese New Year ! ! !
At the beginning of the new year, everything is renewed, on the occasion of this new year, we sincerely thank our customers for their support and co-operation with us in the past year. In the new year, our company will work harder to provide you with better service, our Spring Festival holiday arrangements are as follows: from 9th February 2024 to 18th February 2024. We hope you could understand the inconvenience caused by the holiday. We will arrange a special person to reply the message and make the projects run normally. We wish you all a happy Chinese New Year and a happy family!
Ticagrelor: the World’s First Reversible Combination Orally-administered P2Y12 Adenosine Diphosphate Receptor Antagonist
Ticagrelor, a new platelet aggregation inhibitor, is the world’s first reversible combination orally-administered P2Y12 adenosine diphosphate receptor antagonist. It is used to reduce cardiovascular death and heart attacks in patients with acute coronary syndrome. Ticagrelor is white to off-white powder with hygroscopic, so low temperature storage and transport is required. Mechanism Ticagrelor has reversibly acts on the 2 purine receptor subtype P2Y12, of vascular smooth muscle cells (VSMC,) which does not require metabolic activation, and has a significant inhibitory effect on platelet aggregation induced by adenosine diphosphate. In this case, platelet function will recover rapidly after stopping the dose. Features Rapid onset of action Ticagrelor can be absorbed in approximately 1.5 hours and After about 2.5 hours, ticagrelor can rapidly transformed into circulating metabolite AR-C124910XX. The mean bioavailability of ticagrelor was approximately 36%. Powerful drug Without increasing major bleeding, ticagrelor treatment for 12 months significantly reduced the risk of cardiovascular death by 21% compared with clopidogrel. Ticagrelor is already a first recommended drug for cardiovascular disease in Europe. Platelet function recovered quickly The interaction between ticagrelor and platelet P2Y12 ADP receptor is reversible, without conformational change and signal transmission, and platelet function in blood recovers rapidly after drug withdrawal. Sythesis Ticagrelor is mainly composed of three major fragments: a five-membered ring, a thioether pyrimidine, and a three-membered ring. At present, a variety of synthesis routes have been reported, and the common point is that there is no construction of chiral centers in the synthesis process, and all the six chiral centers are introduced by starting materials. In this synthetic route, starting materials S1 and S2 were coupled, then the ring was diazosed off under the conditions of sodium nitrite and acetic acid, and then coupled with starting material S3. Finally, the finished product of ticagrelor was obtained by removing the forkone protection. Usage and dosage Oral administration. This product can be taken before or after meals. The initial dose was a single dose of 180 mg, followed by 90 mg twice a day. It should be used in combination with aspirin unless clearly contraindicated. After the initial loading dose of aspirin, aspirin was maintained at a dose of 75 to 100mg once daily. Ticagrelor can be started in ACS patients who have already received a loading dose of clopidogrel. Treatment may be given for up to 12 months unless there is a clinical indication to discontinue treatment. Cautions The most frequently reported adverse effects were dyspnea, contusion, and epistaxis in patients who received ticagrelor, which occurred more frequently than in patients who received clopidogrel. Among patients with acute coronary syndromes who are treated with ticagrelor combined with aspirin, there is an increased risk of bleeding. Therefore, the increase of bleeding risk should be balanced against the benefit of preventing atherothrombotic events. Interruptions of ticagrelor tablets should be avoided. If ticagrelor must be temporarily discontinued, treatment should be restarted as soon. The risks of myocardial infarction, thrombosis, even death would increase if ticagrelor is discontinued.
Fosfomycin Tromethamine, a Broad-Spectrum Bactericidal, Especially for Lower Urinary Tract Infections.
Fosfomycin is a broad-spectrum bactericidal for human and animals purposes, which inhibits the growth of E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc.. Fosfomycin tromethamine is a phosphonic acidepoxide derivative, which expands the therapeutic utility of fosfomycin salt because its water solubility increased enough to allow oral administration. This compound is a white to off-white powder with great hygroscopic and solubility in water. Mechanism Fosfomycin tromethamine, is a derivate of fosfomycin, which was initially isolated from fermentationsof streptomyces spp and been used as human medicine and veterinary medicine for over 50 years. Fosfomycin can inactivate the first enzyme in the bacterial cell wall biosynthesis pathway, which occurs through nucleophilic opening of the epoxide ring. Fosfomycin tromethamine only acts on the bacterial cell wall, human cells do not have this target site and is not affected. In this case this compound can be used in pregnant women, children and elderly patients. Features Broad spectrum antibiotic Fosfomycin sodium is a broad-spectrum antibiotic of Gram-positive and Gram-negative bacteria, for instance E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc. and is particularly suitable for the treatment of acute cystitis Rapid sterilization After oral administration, fosfomycin tromethamine is rapidly decomposed into fosfomycin and tromethamine in the body. With the characteristics of low molecular weight and high hydrophilicity, fosfomycin tromethamine appears good distribution in fluid and strong penetration. So this medicine can widely distribute in body fluid and tissue to increase curative effect. Tromethamine is a weakly osmotic diuretic, which can alkalinize urine and effectively reduces the symptom of urinary tract irritation. Low toxicityand residue of Fosfomycin tromethamine Bioavailability of Fosfomycin tromethamine by oral administration is from 34% to 41% in healthy adults, 37% in fasting and 30% after eating. It shows little irritation on the body, no acute toxicity and adverse reactions. The maximum plasma concentration was reached within 2 to 2.5 hours after dose, and will be excreted mainly in its original form in urine and feces in 48h. Sythesis The synthesis of fosfomycin tromethamine use fosfomycin sodium as an intermediate. Prepare a certain concentration tromethamine-sulfuric acid solution and then it was added to fosfomycin sodium aqueous solution by drop. After that the sodium sulfate solid is precipitated with methanol and the filtrate is crystallized at low temperature with n-butanol to obtain fosfomycin tromethamine. Fosfomycin Tromethamine Clinical Application Fosfomycin tromethamine is used for the treatment of acute uncomplicated lower urinary tract infections caused by sensitive bacteria (such as acute cystitis, acute onset of chronic cystitis, acute urethrovesical syndrome, non-specific urethritis, asymptomatic bacteriuria during pregnancy, and urinary tract infections after surgery) and for the prevention of urinary tract infections during surgery and infections caused by diagnostic procedures of the urinary tract. Usage and dosage Adults: single-dose treatment, 3g active ingredient per course; Clinical symptoms usually resolve 2 to 3 days after treatment. For preventing infections caused by surgical procedures and urinary tract care: 6g active ingredient per dose, with first dose taken 3 hours before surgery and second dose taken 24 hours after surgery. Cautions The main symptoms of fosfomycin tromethamine were are diarrhea and soft stools, occasional rash and nausea, which will disappear after drug withdrawal. It is not known whether fosfomycin tromethamine is excreted in human milk, but given the potential for serious adverse effects of fosmycin tromethamine in lactating infants, it should not be administered to lactating women. The efficacy and safety of fosfomycin tromethamine in children aged 12 years and younger are lack of sufficient and well-designed clinical verification.
Baloxavir Marboxil a New Drug against Influenza with Noval Mechanism
Baloxavir Marboxil is a new anti-influenza drug developed by Shionogi Pharmaceutical from Japan and Roche from Switzerland. The drug was first approved for use in Japan in February 2018 and later by the FDA in October for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours. Baloxavir marboxil is a cap-endonuclease inhibitor, which has a unique mechanism of action to Inhibit the proliferation of influenza virus. Mechanism Baloxavir marboxil is a prodrug that enters the body and is hydrolyzed to the active substance baloxavir, which plays an anti-influenza virus activity. Baloxavir is a selective inhibitor of influenza cap-endonuclease, an enzyme required for viral gene transcription and replication, which prevents polymerase function and influenza virus mRNA replication. It has therapeutic activity against both influenza A and B virus infections, even strains resistant to current antiviral drugs. Baloxavir marboxil inhibits an enzyme of viral replication, thus the flu virus infection can be rapidly treated and the symptoms will be alleviated. Features New antiviral influenza drug Baloxavir marboxil is the first anti-influenza virus drug with a new mechanism in the past 20 years. Cpmpared with traditional anti-influenza drugs, Baloxavir Marboxil selectively inhibits the CAP-endonuclease of influenza virus, thereby preventing polymerase function and influenza virus mRNA replication.This unique mechanism gives Baloxavir Marboxil a unique advantage against influenza viruses. Excellent activity of anti influenzavirus Baloxavir marboxil has excellent anti-virus performance against influenza, including influenza A virus (IAV) and influenza B virus (IBV). A single dose of Baloxavir marboxil was shown to be superior to placebo in relieving influenza symptoms and superior to both oseltamivir and placebo drug in virologic outcomes (marked by decreased viral load). Highly effective and long acting drug Baloxavir marboxil is a prodrug. By oral administration, almost all baloxavir marboxil is converted to the active constituent baloxavir. The tmax of Baloxavir to reach the Cmax in vivo is about 4 hours on average. The average half-life of bacalovirda in vivo is approximately 80 hours, so only one dose is needed for most patients. These make Baloxavir marboxil a highly effective and long acting drug. Synthesis The synthesis of Baloxavir marboxil mainly divided into two parts. In each part, a main intermediate is synthesized separately. In the synthesis of intermediate A (1985607-83-7), 7-(Benzyloxy)-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione (intermediate A-2, 1370250-39-7) yields the intermediate A by cyclization and reduction reactions. The coupling of the intermediate A and intermediate B was carried out under dehydration conditions of 1-propanephosphonic anhydride (T3P) and methanesulfonic acid at 70℃ to obtain protected Baloxavir N-2. Compound N-2 was then reacted with 0.6 equivalents of PhBr and K2CO3. Debenzylation was then carried out using LiCl in CH3CONMe2 to give Baloxavir acid in 94% yield. In the final step, Baloxavir acid was reacted with chloromethyl methyl carbonate in dimethylacetamide in 93% yield to form Baloxavir marboxyl. Usage and dosage The Baloxavir Marboxil is used for the treatment of acute uncomplicated influenza in patients (adults and pediatric patients 5 years of age and older) who have been symptomatic for no more than 48 hours. Baloxavir marboxil should be taken as a single dose as soon as possible and within 48 hours of influenza symptom onset for treatment of acute uncomplicated influenza. The specific dose should be adjusted according to the patient’s weight as follow: 20 kg to less than 80 kg: 40mg At least 80 kg: 80mg Cautions Hypersensitivity such as anaphylaxis, angioedema, urticaria, and erythema multiforme may occur or be suspected. Increased incidence of treatment-emergent resistance in patients less than 5 years of age. Baloxavir Marboxil has not been shown to prevent serious bacterial infections, which may begin with influenza-like symptoms or may coexist with, or occur as, a complication of influenza.
Merry Christmas and a prosperous New Year!
Merry Christmas and a prosperous New Year!
Semaglutide Starts the New Life with Type 2 Diabetes
Semaglutide, brand names as Ozempic, Wegovy, and Rybelsus, is an anti-diabetic drug developed by Novo Nordisk, which is used to treat type 2 diabetes and manage chronic weight. With good hydrophilicity, low renal excretion, long half-life in the body, It has great ability to control blood glucose level with great convenience by injection once a week. Semaglutide is white or pale-yellow lyophilized powder, so low temperature storage and transport is required. Mechanism Semaglutide is a glucagon-like peptide-1(GLP-1) receptor agonist with 94% sequence homology with human GLP-1. It increases the production of insulin, which can lower the blood glucose level. Semaglutide also appears to enhance growth of β cells, sites of insulin production, in the pancreas. By lowering appetite and slowing down digestion in the stomach, Semaglutide also can reduce food intake to control body weight. Features Safe and stable blood glucoselevel control Semaglutide has a blood glucose concentration-dependent effect, which can increase pancreas responsiveness to glucose and inhibit the glucagon secretion. When blood glucose is lowered, this effect is diminished synchronously. So the risk of hypoglycemia will be lowered. User-friendly Maximum concentrations of Semaglutide were reached 1-3 days after administration. Steady-state exposure was reached after 4 to 5 weeks of once-weekly dosing. Compared with native GLP-1, Semaglutide has a longer half-life, approximately 1 week. Patients with type 2 diabetes can achieve good blood glucose control with only one injection per week. Cardiovascular and renal protection effects Multiple studies have shown that Semaglutide can significantly reduce the risk of adverse cardiovascular events and stroke. Semaglutide is also reported to reduce the proteinuria, uric acid, glomerular sclerosis. Manage chronic weight Semaglutide also can reduce food intake to control body weight, by lowering appetite and slowing down digestion in the stomach. FDA approved usage of Semaglutide for long-term weight control. Sythesis The synthesis of Semaglutide mainly contains two methods, fermentation and chemical synthesis. In fermentation method, several bacterial strains are chosen to product Semaglutide precursor. After the precursor is purified, further reaction undergoes to obtain Semaglutide. In chemical synthesis, Semaglutide’s long peptide chain is divided into four parts, intermediate 1, 2, 3 and 4. Each intermediate is synthesized separately, and finally synthesizes to Semaglutide. Additionally, intermediate 1 has a side chain, which should be synthesized previously. Semaglutide side chain Semaglutide intermediate 1 Semaglutide intermediate 2 Semaglutide intermediate 3 Semaglutide int 4 Usage and dosage The starting dose of Semaglutide was 0.25mg once weekly. After 4 weeks, dose should be increased to 0.5mg once weekly and adhere for at least 4 weeks. Whereafter, dose may be increased to 1 mg once a week, in order to further improve blood sugar control level. Weekly dose of more than 1mg is not recommended. Cautions Reported adverse effects in clinical trials of Semaglutide were gastrointestinal disorders, including nausea (very common), diarrhea (very common), and vomiting (common). Usually, these adverse effects are mild and duration is short. Semaglutide should not be used in patients with type 1 diabetes or in the treatment of diabetic ketoacidosis. This product is not a substitute for insulin. Semaglutide is not recommended for patients with grade IV congestive cardiac failure.
Fosfomycin sodium, a broad-spectrum antibiotic of Gram-positive and Gram-negative bacteria with excellent curative effect
Fosfomycin sodium is a compound with the appearance of white or off-white powder at room temperature, hygroscopic, freely soluble in water or aqueous solution. Mechanism Fosfomycin Sodium, is a derivate of fosfomycin, a type of macrolide antibiotics, which was first isolated from Streptomyces fradicle in 1960s and has been used as human medicine and veterinary medicine for over 50 years. Fosfomycin Sodium is a competitive inhibitor of a bacterial cell wall synthesis enzyme, inhibiting the first synthesis reaction of the bacterial cell wall by hindering the utilization of related substances. Features · Broad spectrum antibiotic Fosfomycin sodium is a broad-spectrum antibiotic of Gram-positive and Gram-negative bacteria, for instance E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc. and is wildly used in the treatment of infection of respiratory, urinary, intestinal, genital systems etc.. · Rapid sterilization With the characteristics of low molecular weight and high hydrophilicity Fosfomycin Sodium appears good distribution in fluid and strong penetration. So this medicine can widely distribute in body fluid and tissue to increase curative effect. About 25% of the E. coli were killed at 1 hour after exposured to Fosfomycin Sodium (12.5μg/ml), and all died within 4-6 hours. Pseudomonas aeruginosa and Staphylococcus aureus were also all killed at 4 and 8 hours. · Low toxicity and residue Fosfomycin Sodium shows little irritation on the body, no acute toxicity and adverse reactions. Single dose will be eliminated by kidney in 18-72 hours for muscles and organs to reach the residual standard with no increasing burden on the kidney. · Extensive usage Fosfomycin Sodium is wildly used for human and livestock in all countries with no restriction in regulation. Sythesis The Synthesis of Fosfomycin Sodium starts from fosfomycin phenylethylamine. Basic fosfomycin sodium (PH 9.0-10.5) was obtained through the reaction between fosfomycin phenylethylamine with NaOH or MeONa. Basic crude production recrystallizes in acetone to obtain neutral fosfomycin phenylethylamine. Clinical Application Fosfomycin Sodium is wildly use for the treatment of infections caused by Staphylococcus aureus, Escherichia coli, Proteus and Shigella etc.. It is usually used to treat uncomplicated urinary tract infections and to reduce nephrotoxicity and ototoxicity of platinum-containing anti-tumor agents. It is also used for susceptibility studies of Klebsiella pneumoniae and to study in vitro susceptibility testing procedures for fosfomycin tromethamine. Usage and dosage · Fosfomycin Sodium For Human I.v.drip: dissolve in sterilized water, then dilute it into 250-500ml 5% glucose injection or sodium chloride injection for intravenous infusion. Adult: 4-12g/day in 2-3 times; Child: 0.1-0.3 per kg/day in 2-3 times. · Fosfomycin Sodium On Veterinary Drinking water：5-10g/100kg in water, twice daily for 3 days; Mixed feed: 10-15g/100kg in feed, twice daily for 3 days. Combination therapy Intestinal infections: combine with β-lactam, aminoglycoside; Respiratory and lung infections: combine with macrolides, β-lactam; Staph infections: combine with erythromycin, rifampin; Acute respiratory infections, sepsis, peritonitis etc.: increase the dose and combine with β-lactams or aminoglycosides. Cautions It may cause mild gastrointestinal reaction as Fosfomycin Sodium‘s Side Effects, for instance nausea, anorexia, epigastric discomfort, loose stools or mild diarrhea, which generally does not affect the continuous dosing. Phlebitis is occasionally reported at high dose and rapid drip in i.v.drip, so the speed of drip should be in control. Liver function should be monitored in large-dose therapy. When use as veterinary medicine, Fosfomycin Sodium used for pigs, chickens and fish mainly; therapy for other animals should be under veterinary guidance.
