24729-96-2 Usage
Description
Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic clindamycin, which is derived from lincomycin, a lincosamide. It exhibits a zwitterionic structure, making it highly soluble in water. Clindamycin phosphate has primarily bacteriostatic action against Gram-positive aerobes and a wide range of anaerobic bacteria. It is available for both topical and parenteral (intravenous or intramuscular) administration, making it suitable for treating various infections and conditions.
Used in Pharmaceutical Industry:
Clindamycin phosphate is used as a broad-spectrum antibiotic for the treatment of serious infections, such as respiratory tract infections, septicaemia, peritonitis, and bone infections. Its bacteriostatic action and wide range of activity against both aerobic and anaerobic bacteria make it an effective treatment option.
Used in Dermatological Applications:
Clindamycin phosphate is used topically as an antibiotic for the treatment of inflammatory acne vulgaris, either alone or in conjunction with benzoyl peroxide. It is particularly effective when used with benzoyl peroxide or topical retinoids, as clinical studies have shown that combination therapy can result in a reduction of total lesion counts by 50-70%. However, the potential for serious adverse gastrointestinal effects and the risk of bacterial resistance should be considered when prescribing topical clindamycin therapy.
Used in Injectable Formulations:
Clindamycin 2-phosphate is a salt of clindamycin that is prepared by selective phosphorylation of the 2-hydroxy moiety of the sugar of clindamycin. The introduction of the phosphate group improves the solubility of the compound, making it suitable for injectable formulations. This allows for parenteral administration (intravenous or intramuscular) for the treatment of serious infections or instances when oral administration is not feasible. Solutions of clindamycin phosphate are stable at room temperature for 16 days and for up to 32 days when refrigerated.
Chemical Properties:
Clindamycin phosphate is a solid or colorless solution with a characteristic alcohol odor. Its chemical properties include its zwitterionic structure and high solubility in water, which contribute to its effectiveness as an antibiotic and its stability in various formulations.
Indications
Clindamycin Phosphate Topical Solution and Clindamycin Phosphate Lotion (Clindamycin Phosphate Topical Suspension USP, 1%) contain clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per milliliter. Clindamycin Phosphate Gel contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram.
Clindamycin Phosphate is indicated for topical application in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate.
CLINICAL PHARMACOLOGY
Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Cross resistance has been demonstrated between clindamycin and lincomycin.
Antagonism has been demonstrated between clindamycin and erythromycin.
Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in the serum (0 to 3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin.
Clindamycin activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of Clindamycin Phosphate Topical Solution for 4 weeks was 597 mcg/g of comedonal material (range 0 to 1,490). Clindamycin in vitro inhibits all Propionibacterium acnes cultures tested (MICs 0.4 mcg/mL). Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin.
Pharmacokinetics
In an open label, parallel group study of 24 patients with acne vulgaris, once-daily topical administration of approximately 3-12 grams/day of clindamycin phosphate gel for five days resulted in peak plasma clindamycin concentrations that were less than 5.5 ng/ml.
Following multiple applications of clindamycin phosphate gel less than 0.04 % of the total dose was excreted in the urine.
Biological Activity
Clindamycin 2-phosphate is an aminoglycoside antibiotic that has been used to study the cytoxicity of antibiotics on human cell lines, Bacterial protein synthesis and peptide translation, and the inhibition of human Tyrosyl-DNA Phosphodiesterase.
Clindamycin 2-phosphate is a pharmacological tyrosyl-DNA phosphodiesterase (Tdp1) inhibitor. Clindamycin 2-phosphate can repair DNA topoisomerase I-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. It inhibits protein synthesis in bacteria by binding the 50s ribosomal subunit. ?
Spectrum of Activity: Gram positive cocci and taxoplasma. Especially active against anaerobic bacteria.
Mode of Action: Inhibits protein synthesis in bacterial by binding the 50s ribosomal subunit.
Drug interactions
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore it should be used with caution in patients receiving such agents.
Incompatibilities
Clindamycin phosphate is incompatible with natural rubber closures. Aminophylline, ampicillin, calcium gluconate, ceftriaxone, ciprofloxacin,doxapram, drotrecogin alfa (activated), fluconazole, magnesium sulfate,phenytoin sodium, ranitidine, tramadol.
Preparation
Preparation of Clindamycin Phosphate: a solution of 808 mg of the phosphorylated ester in 6 ml of pyridine and 16 ml of acetic acid is stirred at ambient temperature while s5 mg of zinc is rapidly added. The mixture is filtered after one hour and evapo rated to a residue which is heated with stirring at 50°C. for 2 hours with a solvent mixture of 2 ml of acetic acid, and 4 ml of 0.5N sulfuric acid. The mixture is cooled and filtered followed by evaporation of the filtrate in vacuo to a residue, which is chromatographed on a suitable ion-exchange resin, in the acid form, and eluted with 2% ammonium hydroxide. The desired product is obtained as ammonium salt by evaporation of the product fractions. (dec. 212°C)
Pharmacology
Clindamycin phosphate is available in 1% concentration in a hydroalcoholic
vehicle (30 or 60 mL) as a gel or lotion. Although the drug has
not been detected in the blood after topical use, its detection in the urine
suggests that 4% to 5% of topically applied clindamycin is absorbed.
Structure and conformation
Semisynthetic derivative of lincomycin.
Check Digit Verification of cas no
The CAS Registry Mumber 24729-96-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,4,7,2 and 9 respectively; the second part has 2 digits, 9 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 24729-96:
(7*2)+(6*4)+(5*7)+(4*2)+(3*9)+(2*9)+(1*6)=132
132 % 10 = 2
So 24729-96-2 is a valid CAS Registry Number.
InChI:InChI=1/C18H34ClN2O8PS/c1-5-6-10-7-11(21(3)8-10)17(24)20-12(9(2)19)15-13(22)14(23)16(18(28-15)31-4)29-30(25,26)27/h9-16,18,22-23H,5-8H2,1-4H3,(H,20,24)(H2,25,26,27)/t9?,10-,11+,12?,13-,14+,15-,16-,18-/m1/s1
24729-96-2Relevant articles and documents
Synthesis method of clindamycin phosphate and application
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Paragraph 0023; 0029-0030; 0031-0038, (2021/07/17)
The invention belongs to the field of medicine synthesis, and discloses a synthesis method of clindamycin phosphate. The method comprises the following steps: chloridizing tert-butyl (2-chloro-1-(3,4,5-trihydroxy-6-(methylthio) tetrahydro-2H-pyran-2-yl) propyl) carbamate with phosphorus trichloride, esterifying with phosphorus oxychloride, and finally carrying out condensation reaction with 1-methyl-4-propyl pyrrolidine-2-carboxylic acid, so as to obtain the clindamycin phosphate. According to the synthesis method of clindamycin phosphate, molecules with small molecular weight are used as raw materials, so that the purification difficulty of an intermediate is reduced, the recovery rate of the intermediate is improved, and the production cost is reduced. The invention also provides an application of the synthesis method of the clindamycin phosphate, the synthesis method is used for synthesizing the clindamycin phosphate, and the obtained clindamycin phosphate is used for preparing the clindamycin phosphate injection.
Preparation method of clindamycin phosphate
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Paragraph 0051; 0056-0057; 0063-0064; 0070-0071, (2018/03/26)
The invention belongs to the technical field of chemical synthesis and relates to a preparation method of clindamycin phosphate. The preparation method includes preparing clindamycin isopropylidene alkali from clindamycin hydrochloride monohydrate, subjecting the clindamycin isopropylidene alkali to phosphate esterification with phosphorus oxychloride as a phosphate esterification agent and 1,2,4-triazole as an acid-binding agent to obtain isopropylidene clindamycin phosphate, and subjecting the isopropylidene clindamycin phosphate to deprotection by hydrolysis of mixed acid to obtain the clindamycin phosphate. The preparation method has the advantages that by preparing the clindamycin phosphate through one-step hydrolysis of organic acid, the preparation method is energy saving and environment friendly; the preparation method is high in yield and low in cost and can obtain the high-purity finished product directly without subsequent refining, so that the molar yield of the clindamycinphosphate can reach 96.15%; the clindamycin phosphate is good in crystal form (bulk density and liquidity), so that aseptic packaging is benefited.
A clindamycin phosphate ester synthesis method
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Paragraph 0042; 0045-0046, (2017/02/28)
The invention belongs to the technical field of chemical synthesis and specifically relates to a synthetic method of clindamycin phosphate. The method comprises the following steps of synthesis of clindamycin free alkali, ketonization reaction, phosphorylation reaction and aftertreatment. According to the invention, the weight yield of the clindamycin phosphate can reach over 80% by changing a charging sequence, steps and a catalyst.
