Arganil - new antiseptic and hemostatic tool

 

The invention relates to medicine and can be used in surgery, dentistry, gynecology, traumatology, sports medicine, at home, with operating procedures and the damage associated with bleeding, especially in the presence of infection. Describes the substance of the formula (-CH2-CHCOOH-)n- (CH2CHCOOAg)mwhere n=9000-40000; m=100-3000, and the content of silver is 0,0003-0,0009 g-at, and the content of carboxyl groups is 0,0219-0,0213 g-EQ per 1 g of the polymer. It also describes antiseptic and hemostatic agent, representing a compound of the above formula. The technical result of the invention to provide a new drug, which also has antiseptic and hemostatic properties and does not show side effects. 2 C. p. F.-ly, 3 tables.

The invention relates to medicine and can be used in surgery (including purulent), dentistry, gynecology, traumatology, sports medicine, at home, with operating procedures and the damage associated with bleeding, especially in the presence of infection.

It is known that such synthetic electrolytes, as polycarboxylic acid, swaps the connections. 11, 1997, S. 1883-1904), which leads to a hemostatic effect. Based on this principle synthetic hemostatic drug paracril (SU 698622, 1979; Mashkovsky M. D. Medicines. M.: Medicine, 1993, S. 152; Register of medicines of Russia. M: Enfermagem, 1993, S. 870). It is a partial metal salt of polyacrylic acid (PAC), which contains from 0.05 to 0.5% iron, and corresponds to the formula[(CH2-CHCOOH)m-(CH2CHCOOFex1/x)]nwhere m >150, x=2-3, n=50-100. Get paracril polymerization of acrylic acid in the presence of a redox system K2S2O8FeSO4(NH4)2SO46N2[2] . The molecular mass (MM) paracril from 800000 to 1000000 (Rel2,0-2,4; t= 20oC, 1% aqueous solution). When MM or increase the amount of iron in the polymer during the synthesis process of paracril undesired crosslinking, which leads to loss of solubility. Obtained by the method of Abzaeva K. A. and other paracril not possesses antiseptic properties and is very weak against some microorganisms.

However, in practical msih antiseptics is very important. This applies to those cases where therapeutic effect of antibiotics, due to the resistance of pathogenic organisms is very small. Preparations of silver (poviargol, protargol, colloid) (Use of silver preparations with medicine. Preprint 2, Novosibirsk, 1993, S. 61) in this regard favorably with antibiotics and sulfonamides. They have a truly unique properties - suppress pathogens and simultaneously stimulate the immune status.

The technical purpose of this invention to provide a new drug, which also has antiseptic and hemostatic properties, does not show side effects and eliminates the mentioned disadvantages.

This chemical problem is due to the fact that, as a drug with these properties, the proposed incomplete silver salt of polyacrylic acid - aracil (arg - silver, acrylic - acrylic acid). It satisfies the General formula (-CH2-CHCOOH)n-(CH2CHCOOAg-)mwhere n=9000-40000; m=100-3000.

The molecular mass of alacrima is in the range from 800000 - 3000000. The IR spectra of the drug, taken on a Specord IR-75 tablets CVG contain absorption bands carboxyl, carboxylate is liberizatsii acrylic acid in the presence of 0.5-0.6% K2S2O8in water for 60-300 minutes at 80-90oC. the Resulting PAK purified from unreacted monomer and initiator and a 4% solution of this polycarboxylic acid type aqueous solution of silver nitrate (6-16% by weight of the monomer, which corresponds to 3.8-10% silver), mix. If you need a solid substance removing the formed solution of nitric acid. The toxicity of 1% solution of alacrima LD50is >3000 mg/kg, which indicates the relative harmlessness of this connection. Studies of the properties of alacrima in the quality control used paracril obtained by a known method (SU 698622, 1979) and its silver salt.

Example 1.

a) Synthesis of polyacrylic acid with a molecular weight characteristic of paracril (PAK-1).

9 g (0.125 mole) of acrylic acid are dissolved in 45 ml of water. The solution is heated to 80oWith and with stirring, added dropwise 0.045 g K2S2O8(0.5% by weight of the monomer) dissolved in 5 ml. of water. Then the resulting mixture was stirred for 60 minutes at 80-85oC. the polymer Solution cooled, add 50 ml of water and transferred to a column of anion exchange resin. The purified aqueous solution of PAK-1 is dried at 50oC. the Weight of the transparent is T=20oWith, 1% aqueous solution).

Synthesis of alacrima-1 4 g PAK-1 is dissolved with stirring in 70 ml of water, the resulting solution was added 0.24 g (6%) AgNO3(equivalent to 3.8% of Ag) dissolved in 5 ml of water. The solution is stirred for 30-60 minutes, the polymer is dried at 50oC. Weight gray transparent plates 4 g, yield 99%. Found, %: C 47.88, H 5.52, Ag 3.97.

Calculated, %: 48.21, H 5.35, Ag 3.60;Rel= 2.34; n=9800; m=150; in the composition of the polymer is 0.0219 g-EQ carboxyl groups and 0.0003 g-at Ag on 1 g of the polymer[CH2CH(COOH)-]n-[CH2SN(Sooud-]mwhere n=9800, m=150.

Synthesis of alacrima-2 carried out analogously to the synthesis of alacrima-1. To a solution of 4 g of PAK-2 and 70 ml of water is added to 0.63 g (of 15.75%) AgNO3(which corresponds to 10% Ag). Weight alacrima-3 4.5 g, yield 98%. Found, %: C 45.23, H 4.82, Ag 9.87. Calculated, %: C 45.50, H 5.01, Ag 9.61;Rel= 2.33; in the composition of the polymer is 0.0213 g-EQ carboxyl groups and 0.0009 g-at Ag on 1 g of the polymer[CH2CH(COOH)-]n- (CH2CH(COOAg-]mwhere n=9600, m=400.

b) Synthesis of polyacrylic acid with a molecular weight of up to 3 million (PAK-2) is carried out analogously to the synthesis of PAK-1. A solution of 9 g (0.125 mole) of acrylic acid in 36 ml of water heated to 80oTo add 0.054 g (0.6% by weight of the monomer), K2S< PAK-1. The weight of the polymer 8.7, Yield 97%. Found, %: C 50.01; H 5.45. Calculated, %: 50.00, N, 5.59.Rel= 7.06 (T= 20oWith, 1% solution in the presence of 5% such as NaCl).

Synthesis of alacrima-3 carried out analogously to the synthesis of alacrima-1. To a solution of 4 g of PAK-1 and 70 ml of water is added to 0.63 g (of 15.75%) AgNO3(which corresponds to 10% Ag). Weight alacrima-2 4.5 g, yield 98%. Found, %: C At 45.21, H 5.11, Ag 9.98. Calculated, %: 45.15, H 5.29, Ag 10.39;Rel= 7.33; n=40000; m=3000; in the composition of the polymer is 0.0213 g-EQ carboxyl groups and 0.0009 g-at Ag on 1 g of the polymer[CH2CH(COOH)-]n- (CH2CH(COOAg-]mwhere n=40000, m=1700.

Silver salts paracril obtained analogously to araceli-1. To a solution of 4 g of paracril in 70 ml of water is added 0.08 g (2%) AgNO3(which corresponds to 1.3% of Ag), allocate paracril-1 or 0.64 g (15.75%) AgNO3(which corresponds to 10% Ag) and produce paracril-2. Quantitative data in the l-at and g-EQ derived from the elemental analysis shown in the description of the invention. They are calculated by [A. P. Krestov. Fundamentals of analytical chemistry, 1976, so 2, C. 57]. Here is an example of recalculation on the example of obtaining alacrima-1. The content of silver in araceli-1 3.60%, which corresponds to 3.60 g per 100 g of the polymer or 0.036 g per 1 g of the polymer. The molecular weight of the silver 107.8 that corresponds at Ag and g-EQ-COOH groups in alacritech-2 and -3.

Example 2. Determination of microbiological activity.

Antimicrobial activity of alacrima studied in comparison with antibacterial activity PAK and paracril. The study was performed in accordance with the requirements of the State Pharmacopoeia (11th edition, vol. 2, M.: Medicine, 1990) at the Museum of the test strains, and strains of microorganisms isolated from patients with septic center. In two test tubes with 10 ml of thioglycolic environment and two with 10 ml of medium Saburo make 1 ml of the investigated 1% aqueous solution of the polymer. At the same time in each tube add 0.1 ml of the microbial suspension of the corresponding test strain, which contains 1000 cells in 1 ml of Crops in thioglycolate environment incubated at t=35oWith within 72 hours. Control is a fertile environment in which instead of the investigated solutions make 1 ml of distilled water. The obtained data are presented in table 1. The table shows that the solutions of PAK and paracril almost not inhibit the growth of microorganisms. For paracril only in one case there is a slight suppression of microbial growth, apparently due to the presence of small amounts of iron (0.5%) in macromolecules. Antimicrobial action PAK start is consistent with the increase in its quantity and in the presence of 10% is observed suppression of growth of the test organism. Thus, arganil-2 and -3, as well as paracril-2 have strong antimicrobial properties. However, arganil 2 and 3 in its effectiveness not only surpass paracril, but his silver 10% Sol.

Example 3. The definition of the haemostatic potential.

Hemostatic potential PAK, alacrima and paracril was determined in vitro in various pathologies of the blood.

To obtain blood with various disorders of the hemostatic system used canned blood and pooled donor plasma from 10 donors. They created different types of disorders of hemostasis: 1) deficiency of coagulation factors (Hypo - and afibrinogenemia, hemophilia); 2) the excess of anticoagulants; 3) high depenalize (due to the activation of plasminogen by streptokinase, which leads to the formation of plasmin, or by introduction into the blood of kasimasi similar to plasmin). The coagulation time determined by the Lee-white. The fibrinogen concentration is fixed by the photometric method.

Hypocoagulation was achieved by dilution of blood and plasma saline solution (see table 2). As can be seen from the table, at a dilution equal to 0.25, the amount of fibrinogen is reduced below a critical level, and the coagulation time is dramatically slow. When R>/p>In solutions of 0.5 ml with different levels of fibrinogen (i.e., with different cultures only) add 0.4 ml of 1% aqueous solutions of polymers. In the examples presented in 3 columns in the table (fibrinogen concentration from 4 to 1.2 g/l), blood clotting occurs within one to two minutes. Upon further dilution phenomenon hemostasis, where it is observed, characterized by the formation of a weak bunch, which is sealed within an hour. This arganil-3, PAK and paracril. Among the polymers containing up to 10% silver and having the same molecular weight, the worst was paracril-2.

Thus, arganil-3 in addition to antibacterial properties has a powerful haemostatic potential and promotes the formation of clots with a significant deficiency of coagulation factors.

Impact solutions PAK and its derivatives on the anticoagulant activity of blood are presented in table 3. Anticoagulant and fibrinolytic activity create by adding 1 ml of blood 50 IU of heparin, streptophyta or kasimasi respectively. With the introduction of heparin and streptophyta the blood loses its ability to clot, and adding kasimasi the clotting of blood is slowed down 2-3 times. When making these Rasta, streptophyta and kasimasi. With the exception of solutions paracril, which contains a large number of macromolecules silver (10%). Solutions paracril, PAK and alacrima have the ability to neutralize as sodium citrate, and heparin and can be used in the clinic for bleeding associated with high anticoagulant and fibrinolytic activity.

Thus, only arganil has high antiseptic and hemostatic properties.

Claims

1. The substance formula

where n = 9000-40000;

m = 100-3000,

moreover, the content of silver is 0,0003-0,0009 g-at, and the content of carboxyl groups is 0,0219-0,0213 g-EQ per 1 g of the polymer.

2. Antiseptic and hemostatic agent, representing a connection on p. 1.

 

Same patents:

The invention relates to a composition and method for producing a non-ionic and anionic water-soluble polymers in the form of finely dispersed particles of the polymer in aqueous salt environment
The invention relates to the production of water-soluble polymers of acrylic series, which can be used in several branches of engineering and technology, namely as a dressing for finishing textiles, coal mining, and in the processes of purification and clarification of drinking, industrial and waste water as a flocculant, in the drilling technique as a protective means in the chemical industry as the thickening agent

The invention relates to new methods and materials to minimize deposition of metal oxides on the tubes of the steam generator to the secondary line pressure of steam generators in nuclear power plants (NPP) using a polymeric dispersant high purity

The invention relates to the chemistry of polymers, and in particular to a method for producing polymers based on acrylic and methacrylic acid, having a high water absorption

The invention relates to medicine, namely to ophthalmology
The invention relates to medicine

The hemostatic tool // 2219922

The invention relates to medicine, namely to urology
The invention relates to medicine
The invention relates to medicine and can be used in neurosurgery and neurotraumatology and surgery to stop capillary bleeding
The invention relates to medicine, namely to surgery, and can be used for hemostasis surface wounds parenchymatous organs
The invention relates to medicine, in particular to the gynecologist, and for the treatment of chronic adnexitis

The invention relates to medicine, specifically to the means which have an antimicrobial effect on local purulent-inflammatory processes of the soft tissues and used in surgery, dermatology, obstetrics, gynecology, otolaryngology
The invention relates to General surgery, traumatology and military surgery and can be used for preoperative treatment of the skin and the processing of the wound surfaces operating and traumatic wounds
The invention relates to pharmaceutical industry

The invention relates to medicine, in particular to purulent surgery in the treatment of abscesses and phlegmon, as well as burn wounds
Up!