Hydroxyethylphosphonate of guanidine with antiseptic and antidote properties
(57) Abstract:The invention relates to chemistry and medicine and relates to a new hydroxyethylphosphonate the guanidine of the General formula
< / BR>where n = 4-30, highly antiseptic and antidote properties, exceeding the efficiency properties are widely known foreign antiseptic - of chlorhexidine digluconate. New antiseptic due to its polymeric structure has low toxicity compared to known drugs. 3 table. The present invention relates to the field of medicine and can be used in surgery and other clinical disciplines where occurrence of infection and also to prevent intoxication by heavy metals.The greatest distribution in the fight against infection drugs nitroimidazole series or chlorhexidine .Derivatives metronidazole quickly absorbed from the stomach and intestines. They are well tolerated, although 8% of cases of nausea, dizziness, itching and sweating, passing quickly after discontinuation of the drug.The closest analogue of this invention is chlorhexidine will bigcone for viruses and spores .When using this drug having an unpleasant taste, there is dryness and itching of the skin, dermatitis. Appears allergenic and irritant effects. In addition, chlorhexidine digluconate is an imported drug, manufactured by ICI, UK. Antidote properties of chlorhexidine digluconate was not found.The technical purpose of this invention to provide a new drug, which has antiseptic and antidote properties, low toxicity and eliminates these drawbacks. The drug is less toxic and is made from domestic raw materials.This technical problem is solved by the fact that, as a drug with these properties, proposed hydroxyethylphosphonate of guanidine (GFPG), having the General formula:
< / BR>where n=4-30.It is obtained from hydrochloride, guanidine consistent treatment of this salt with sodium ethylate, a solution of 1-hydroxyethylene-bis-phosphonic acid (califona).Parameters toxicity phosphonate, guanidine low-toxic substance (PL. 1).The drug is absorbed through intact skin. Though the nom absorption occurs in the first five minutes of contact. Dries on the surface, the solution hydroxyethylphosphonate the guanidine forms a polymer film, which prevents further resorption of antiseptics through the skin and makes it less toxic than chlorhexidine digluconate.Set forth the invention is illustrated in the examples.Example 1
Getting hydroxyethylphosphonate the guanidine
16,1 g (0,02 mol) of the hydrochloride, guanidine dissolved in 100 ml of ethanol and added to the solution ethylate sodium obtained from 2,3 (in 0.104 mole) of sodium in 50 ml of alcohol. Stirred at 10oC. the Precipitated sodium chloride is filtered and to the filtrate was added with stirring a solution of 20,60 (0,1 mole) of 1-hydroxyethylene-bis-phosphonic acid in 180 ml of ethanol. Precipitated white precipitate hydroxyethylphosphonate the guanidine is separated by decantation, washed with alcohol and ether and dried in vacuum at 40-50oC.Output to 32.7 g (91%)
C 28,55; H TO 6.80; N 12,78; P 18,26
C WEIGHING 28.32; H 6,38; N 12,69; P 18,73
Determination of microbiological activity hydroxyethylphosphonate of guanidine (GFPG)
In the work on the identification of ICRI is lucont. Tested preparations were diluted concentrations of 1.36; 0,136 and 0,0136%. For setting the experiment was prepared by standard suspension test cultures of bacteria. Density culture corresponded to 1010and CFU/ ml, exposure time of 0.5, 1, 3 and 5 minutes After which the test strains were sown in a nutrient medium KCA and the study drug in the appropriate concentrations. The light of the growth of bacterial colonies on solid nutrient media was performed after 48 h of incubation at 37 ° oC. the Results of the determination of the minimum bacteriological concentrations are presented in table. 2.Table 2 shows that hydroxyethylphosphonate the guanidine strength of antimicrobial action is much more effective than the widely known foreign antiseptic is chlorhexidine digluconate. The proposed drug is produced from domestic raw materials. It has a lower toxicity than is widely known for imported drug chlorhexidine digluconate.Example 3
Study on the application of hydroxyethylphosphonate the guanidine for removing metals from the body of warm-blooded animals
Hydroxyethylphosphonate the guanidine method to form (in vitro) with metals is trigardon in 1/10 part of the maximum tolerated dose, that was in terms of metal, 0.4 mg/kg Hydroxyethylphosphonate polyhexamethylene guanidine was also introduced intragastrically within two weeks after nucleating mercury, 1/5-1/20 part from DL50.After detalizacii animals in the urine, liver and kidney were determined by mercury.The results determine the level of mercury in biological media experimental animals are presented in table 3.As can be seen from table 3, entered GFPG after 2-12 days resulted in increased mercury in the urine, and therefore the removal of this metal from the body by an average of 52%. Decreased levels of metal content and internal organs. Thus, in liver tissue by 43%, and in the kidneys to 77,5% compared to the control. Moreover, the dose differences in the introduction of these compounds do not have a significant effect on the excretion of mercury from the body of rats in acute experiments. Therefore, the results indicate the ability hydroxyethylphosphonate the guanidine to bind and remove the metal from the body of warm-blooded animals, which indicates the presence of his antidote properties.Literature:
1. M. D. Mashkovsky Drug sa formula
< / BR>where n = 4 to 30.
FIELD: experimental medicine.
SUBSTANCE: on should introduce solution into fracture area at the following ratio of ingredients, g/l: 1-hydroxyethylidenediphosphonic acid 1.80 - 2.06, water-free calcium chloride 1.44 - 2.22, gadolinium (III) nitrate hexahydrate 0.30 - 0.40, dysprosium (III) chloride hexahydrate 0.038 - 0.076, moreover, solution's pH corresponds to 7.3 - 7.8. The present innovation enables to shorten the process of bony tissue regeneration in the site of its lesion or defect and, also, shorten the period for restoring normal physiological function of traumatized bone.
EFFECT: higher efficiency of regeneration.
22 ex, 1 tbl
FIELD: organophosphorus compounds, medicine.
SUBSTANCE: invention relates to new biologically active phosphonate compounds. Invention describes phosphonate compound of the formula:
wherein R1 and R'1 represent independently hydrogen atom (-H) substituted possibly with -O-(C1-C24)-alkyl, -O-(C1-C24)-alkenyl, -O-(C1-C24)-acyl, -S-(C1-C24)-alkyl, -S-(C1-C24)-alkenyl or -S-(C1-C24)-acyl wherein at least one among R and R'1 doesn't represent -H and wherein indicated alkenyl or acyl comprise from 1 to 6 double bonds; R2 and R'2 represent independently -H substituted possibly with -O-(C1-C7)-alkyl, -O-(C1-C7)-alkenyl, -S-(C1-C7)-alkyl, -S-(C1-C7)-alkenyl, -O-(C1-C7)-acyl, -S-(C1-C7)-acyl, -N-(C1-C7)-acyl, -NH-(C1-C7)-alkyl, -N-((C1-C7)alkyl)2, oxo-group, halogen atom, -NH2, -OH or -SH; R3 represents phosphonate derivative of nucleoside or biphosphonate; X represents compound of the formula:
L represents a valence bond or a bifunctional binding molecule of the formula: -J-(CR2)t-G- wherein t is a whole number from 1 to 24; J and G represent independently -O-, -S-, -C(O)O- or -NH-; R represents -H, unsubstituted or substituted alkyl or alkenyl; m means a whole number from 0 to 6; n = 0 or 1. Also, invention describes pharmaceutical compositions comprising phosphonate compounds, method for treatment of osteoporosis in mammal, method for increasing mineral osseous density, method for prophylaxis of apoptosis of osteoblasts and osteocytes in mammal, method for treatment of viral infection in mammal, method for treatment of growing neoplasm in mammal and method for proliferation of cells. Invention provides preparing new compounds eliciting useful biological properties.
EFFECT: valuable medicinal properties of phosphonate compounds.
17 cl, 2 dwg, 7 tbl, 21 ex
FIELD: chemistry of organophosphorus compounds, medicine, pharmacy.
SUBSTANCE: invention relates to new compounds of the formula (1) showing affinity to one or more GABAB receptors and their pharmaceutically acceptable salts, solvates and stereoisomers but with exception for racemate of (3-amino-2-hydroxypropyl)-phosphinic acid. Invention provides increasing the therapeutic index value.
EFFECT: improved and valuable properties of compounds.
14 cl, 1 tbl, 21 ex
SUBSTANCE: the suggested treatment should be performed due to introducing a compound of total formula I.
EFFECT: increased efficiency of therapy.
17 cl, 1 dwg, 7 ex, 8 tbl