RU2262925C2 - Gel-like preparation for local anesthesia - Google Patents

Abstract

FIELD: medicine, urology.

SUBSTANCE: the present innovation deals with means for external application. The suggested gel-like preparation contains hydroxyethylcellulose polymer as a gel foundation, lidocaine hydrochloride, an antiseptic component - benzalconium chloride (50%), gentamycin and water. The remedy is nontoxic and easy in application, it demonstrates no unfavorable side irritating action being of high penetrating capacity of active components.

EFFECT: higher efficiency of application.

1 cl, 1 dwg, 7 ex

Description

The invention relates to the field of therapeutic agents, namely, external use in the field of urology.

Known tool "Katejel" ("Cathejell") containing 0.05 g of chlorhexidine dihydrochloride per 100 g of gel, as well as "Katedzhel with lidocaine" containing 0.05 g of chlorhexidine dihydrochloride and 2 g of lidocaine per 100 g of gel, manufactured by the pharmaceutical company "Montavit", Austria, which is a sterile, water-soluble gel for external use in a sterile package, with dielectric properties, antiseptic and local anesthetic pharmacological action and intended for catheterization of the urethra, endoscopic studies second, small gynecological procedures (Register of Pharmaceutical Substances of Russia Encyclopedia of Drugs:. ezhegod collection Vyp.10 M., 2003. S.389...).

The disadvantages of the known means "Katedzhel" are: insufficient sliding (lubricating) properties, poorly expressed transport effect of the physiologically active principle, lack of anti-inflammatory effect.

Digenten is also known - a combined gel-like preparation containing gentamicin sulfate, lidocaine hydrochloride, ethonium (antiseptic), used for local anesthesia and disinfection in gynecological studies, cytourethroscopy (Mashkovsky MD Medicines. 2 vol. Ed. Kharkov: Torsing. 1997.V.2. P.269).

A disadvantage of the known agent is the use of ethonium as an antiseptic, which refers to bis-quaternary ammonium bases, has a higher bactericidal activity against streptococci, staphylococci and is used mainly externally. In contact with mucous membranes, can cause severe irritation, less effective against a wide range of bacteria. In addition, the known agent has insufficient elastic properties, which can lead to traumatic insertion of a catheter.

Thus, the authors were faced with the task of developing the composition of the product, which would have an increased sliding (lubricating) and elastic effect and provide the most effective transport through the mucous membrane of active components (anti-inflammatory, antispasmodic, antiseptic), would be non-toxic, would not exhibit undesirable side effects, would convenient to use.

The problem is solved by using a means for research and treatment in urology, containing a gelling biopolymer, a disinfecting (antiseptic) component, lidocaine, gentamicin and water, which contains hydroxyethyl cellulose as a gelling biopolymer, and benzalkonium chloride as a disinfecting component, in the following ratio of components (wt.%):

hydroxyethyl cellulose 0.80-1.20 benzalkonium chloride (50%) 0.04-0.06 lidocaine 0.90-1.10 gentamicin 0.08-0.12 water rest   up to 100

In this case, the agent may contain papaverine in an amount of 0.08-1.20 wt.% Of the total.

Currently, the composition of the means for research and treatment in urology, which contains these components in the proposed qualitative and quantitative ratio, is not known from the patent and scientific and technical literature.

The proposed tool for research and treatment in urology, containing a gelling biopolymer, a disinfecting (antiseptic) component, lidocaine, gentamicin, and water, can be obtained as follows. In a stainless steel reactor equipped with a propeller stirrer, lidocaine (0.90-1.10 wt.%), Gentamicin (0.08-0.12 wt.%), Benzalkonium chloride (0.04-0.06 wt.%) And water are loaded to 100 wt.%, Adjusted mixture to a degree of homogeneity. With vigorous stirring, hydroxyethyl cellulose (0.80-1.20 wt.%) Is added until a homogeneous suspension is formed and then until the mass thickens. The mass is left to stand for 12 hours. The finished product is packaged.

If the product contains papaverine in an amount of 0.80-1.20 wt.% From the total, it is added to the initial mixture, which is then brought to a degree of homogeneity.

Hydroxyethyl cellulose, used as a gelling biopolymer, is a substance of natural origin, predictably affects the human body, is able to degrade, included in natural metabolic chains, provides high transport ability of physiologically active components of the drug and does not have undesirable side effects. The content of the gelling agent less than 0.80 wt.% Does not provide sufficient elastic and sliding properties of the proposed tool. When the content is more than 1.20 wt.%, The transport function of the gel worsens, and the absorption of active components slows down. In addition, there are technological difficulties in obtaining the gel, namely, it is difficult to uniformly mix the solution and packaging of the finished product.

Used as a disinfecting (antiseptic) component benzalkonium chloride is highly soluble in water and alcohols. It is well tolerated by the skin and mucous membranes. It has a microbostatic and bactericidal effect on gram-positive, in large doses - on gram-negative bacteria and candida. The mechanism of antimicrobial action is the same as that of cationic surfactants, but it is less irritating to the mucous membranes. In addition to antiseptic, has a deodorizing effect (Krasilnikov A.P. Handbook of antiseptics. Minsk: Higher school. 1995. P.71). The lower limit (0.04 wt.%) Is sufficient for the manifestation of an antiseptic effect, and in addition, does not violate the required structure of the gel. The upper limit (0.06 wt.%) Is due to the amount that does not yet have an undesirable effect on the human body, and also does not violate the required gel structure. Used as an anesthetic (local anesthetic) component of lidocaine - a strong local anesthetic that causes all types of local anesthesia, it is used in the form of a 1-2% solution to lubricate the mucous membranes (Mashkovsky MD Medicines. 2 vol. Ed. 13th Kharkov: Torsing. 1997. T.1. P.300). The lower limit (0.90 wt.%) Is sufficient for the manifestation of a local anesthetic effect. The upper limit (1.10 wt.%) Is due to the amount that ensures efficient transport of the component through the mucous membranes and does not have an undesirable effect on the human body.

Gentamicin, used as an anti-inflammatory component, is an antibiotic-aminoglycoside. It is used for various infectious diseases caused by microorganisms sensitive to it, and is effective for urinary tract infections. One of the main means of treating severe purulent infections, has a wide spectrum of action, in some cases it is effective in case of insufficient activity of other antibiotics (Mashkovsky M.D. Medicines. In 2 vols. Edition 13th. Kharkov: Torsing. 1997. T. 2. S.268). The lower limit (0.08 wt.%) Is sufficient for the manifestation of anti-inflammatory effect. The upper limit (1.12 wt.%) Is due to the amount that does not yet have an undesirable effect on the human body. The claimed content of gentamicin in combination with other components of the proposed tool provides its effective transport through the mucous membranes of the upper urinary tract, in the kidney, localizing the inflammatory process.

Used when necessary as an antispasmodic component, papaverine is a myotropic antispasmodic, a class of alkaloids. It reduces the tone and reduces the contractile activity of smooth muscles, has a vasodilating and antispasmodic effect (Mashkovsky MD Medicines. 2 vol. Edition 13th. Kharkov: Torsing. 1997. V.1. C.430). The lower limit (0.80 wt.%) Is sufficient for the manifestation of antispasmodic action. The upper limit (1.20 wt.%) Is due to the amount that does not yet have an undesirable effect on the human body. The claimed content of papaverine ensures its efficient transport through the mucous membranes of the lower urinary tract, causing them to relax, while muscle tone is maintained in the upper urinary tract, which is especially important for postoperative operations and is much more effective than the introduction of an antispasmodic component intravenously.

The proposed technical solution is illustrated by the following examples.

Example 1. In a stainless steel reactor equipped with a propeller stirrer, lidocaine 90.00 g (0.90 wt.%), Gentamicin 8.00 g (0.08 wt.%), Benzalkonium chloride 4.00 g (0.04 wt.%) And water 9818.00 g (98.18) are charged wt.%), bring the mixture to a degree of homogeneity. With vigorous stirring, 80 g (0.80 wt.%) Hydroxyethyl cellulose is added until a homogeneous suspension is formed and then until the mass thickens. The mass is left to stand for 12 hours. The finished product is packaged.

Example 2. In a stainless steel reactor equipped with a propeller stirrer, lidocaine 110.00 g (1.10 wt.%), Gentamicin 12.00 g (0.12 wt.%), Benzalkonium chloride 6.00 g (0.06 wt.%) And water 9752.00 g (97.52) are charged wt.%), bring the mixture to a degree of homogeneity. With vigorous stirring, add hydroxyethyl cellulose 120.00 g (1.20 wt.%) Until a homogeneous suspension is formed and then until the mass thickens. The mass is left to stand for 12 hours. The finished product is packaged.

Example 3. In a stainless steel reactor equipped with a propeller stirrer, lidocaine 110.00 g (1.10 wt.%), Gentamicin 12.00 g (0.12 wt.%), Benzalkonium chloride 6.00 g (0.06 wt.%), Papaverine 80.00 g (0.80 wt.%) and water 9672.00 g (96.72 wt.%), bring the mixture to a degree of homogeneity. With vigorous stirring, add hydroxyethyl cellulose 120.00 g (1.20 wt.%) Until a homogeneous suspension is formed and then until the mass thickens. The mass is left to stand for 12 hours. The finished product is packaged.

Example 4. In a stainless steel reactor equipped with a propeller stirrer, lidocaine 90.00 g (0.90 wt.%), Gentamicin 8.00 g (0.08 wt.%), Benzalkonium chloride 4.00 g (0.04 wt.%), Papaverine 120.00 g (1.20) are loaded wt.%) and water 9658.00 g (96.58 wt.%), bring the mixture to a degree of homogeneity. With vigorous stirring, hydroxyethyl cellulose is added 120.00 g (1.20 wt.%) Until a homogeneous suspension is formed and then until the mass thickens. The mass is left to stand for 12 hours. The finished product is packaged.

A comparison of the lubricating (sliding) action of the proposed product and the well-known "Katedzhel" was carried out experimentally as follows, and the duration of moisture retention by the gel was used as a criterion. The agents are applied to an inert carrier (polyethylene plates) and the water content is monitored at specific time intervals by weighing. Thus, a comparative moisture loss profile was obtained for two formulations: Katedzhel, selected as a prototype, and the proposed composition (wt.%: Hydroxyethyl cellulose 0.80, benzalkonium chloride (50%) 0.04, lidocaine 0.90, gentamicin - 0.08, water - 98.18). It is shown that for, for example, 25 hours, about 80% of the water is stored in the product of the proposed composition, the water loss rate for the Katedzhel product is significantly higher (see drawing).

Example 6. Patient R., 45 years old, was admitted with a diagnosis of stone n / 3 of the left ureter. A transurethral lithotripsy was performed, in which the instrument was treated with the proposed agent, and the agent was also introduced into the ureter on the side of the operation in a volume of 2 ml. A lighter insertion of the instrument into the ureter on the side of the operation was noted compared to Katedzhel. It turned out to be possible to reduce the number of analgesics by 1/4 by reducing the morbidity of the introduction of the instrument and the analgesic effect of the drug. The operation was performed without parenteral administration of antibiotics.

Example 7. Patient M., 37 years old, was admitted with a diagnosis of stone with / 3 of the right ureter. Conducted transurethral lithotripsy, the proposed tool was processed tool. In addition, the drug was introduced into the ureter on the side of the operation in a volume of 2.5 ml. Due to the use of the agent, an easier and more convenient for the patient introduction of the instrument into the ureter on the side of the operation was achieved, the amount of anesthetic drug was reduced by 25% due to a decrease in the invasiveness of the instrument and the analgesic effect of the agent. The operation was performed without parenteral administration of antibiotics.

Thus, the proposed tool for research and treatment in urology has improved properties, namely, high penetrating ability of the active components (anti-inflammatory, antispasmodic, antiseptic), sliding (lubricating) and elastic effect, non-toxic, does not have undesirable side effects. In addition, doctors and patients noted a good appearance of the product and a convenient consistency for use, the absence of an unpleasant odor.

The proposed tool can be used as an effective tool for the treatment of inflammatory, post-traumatic and postoperative diseases in the field of urology, as well as gynecology.

The composition of the product does not include components prohibited for use in products intended for contact with mucous membranes.

Claims (2)

1. A means for local anesthesia in the form of a gel containing a gel base, lidocaine hydrochloride, an antiseptic component - benzalkonium chloride and water, characterized in that it additionally contains gentamicin, and as a gel base - a hydroxyethyl cellulose biopolymer, in the following ratio, wt. %: Hydroxyethyl cellulose  0.80-1.20 Benzalkonium chloride (50%)  0.04-0.06 Lidocaine hydrochloride  0.90-1.10 Gentamicin  0.08-0.12 Water  The rest is up to 100 2. The tool according to claim 1, characterized in that it further comprises papaverine in an amount of 0.80-1.20 wt.% From the total.