UA139723U - BARRIER-PREVENTIVE GEL BASED ON A SOLUTION OF COLLOID SILVER - Google Patents

Abstract

Barrier-prophylactic gel based on a solution of colloidal silver contains as an active pharmaceutical ingredient a solution of colloidal silver with an activity of 45-55 ppm, obtained by the physical method of electrolysis. Additionally, the gel contains as active ingredients bisabolol, D-Panthenol, lysozyme hydrochloride, thymol, zinc sulfate, vitamin E, vitamin A, peppermint essential oil and excipients: glycerin, PEG-40, triglycerides, sodium hyaluronate, sodium algal calcium, dimethicone, propylene glycol, potassium sorbate.

Description

The utility model belongs to the pharmaceutical industry and concerns medical products that are used as a prophylactic barrier agent to protect the nasal mucosa during an increase in the number of respiratory viral infections.

Deterioration of the environmental situation, an increase in the number of respiratory viral infections and allergens contribute to the growth of rhinitis and sinusitis - inflammatory diseases of the mucous membrane of the nose and paranasal sinuses.

The development of new highly effective medical products for the protection of the mucous membrane during the period of nasal infectious diseases remains an urgent problem due to the wide spread of infectious diseases of the nose among the population of Ukraine and the world, as well as the appearance of frequent complications and limitations of both domestic and foreign medical products that would act as protective preventive barrier against the penetration of viral, bacterial infections and allergens on the mucous membrane of the nose.

Nanoparticles of metals and metal oxides are of particular interest in this aspect, because such nanostructures exhibit unique physicochemical, biological, and pharmacological properties, and have pronounced bactericidal, fungicidal, and viricidal potential.

Today, among metal nanostructures with pronounced biocidal properties, the most studied are silver nanoparticles, which are actively used in the development of new medicines, as well as in the creation of medical products, synthetic fabrics and packaging materials with antimicrobial activity, and water disinfection devices.

Silver is also widely used as an antiseptic in the treatment of open wounds and burns.

Nowadays, thanks to the development of nanotechnology, compounds of this metal are returning to medicine as new highly effective antimicrobial agents.

The broad spectrum of antimicrobial action of silver, the lack of resistance to it in most pathogenic microorganisms, low toxicity, as well as good tolerability contributed to the increased interest of doctors around the world in preparations of this metal.

This is due to the growth of allergic complications of antibacterial therapy, the toxic effect of antibiotics on internal organs and suppression of immunity, the occurrence of fungal lesions of the respiratory tract and dysbacteriosis after long-term antibacterial therapy, as well as the appearance of resistant strains of pathogens to the antibiotics used.

The well-known nasal ointment "Pinosol" (perz:/Lymly.ada.cha/cha/riposoY-tag-10-d.pitiyeKIai) containing oils of common pine (Ripe 5imevigi5 eiegoYivit), eucalyptus oil (Yeisaiurii eiPegoivit), thymol (Tputoisht ), tocopherol acetate (Tosoiegoi ana aseiya5), menthol (I emotepipoYisht) and auxiliary substances: butylhydroxyanisole (E 320) labrafil M wax white vaseline white.

The well-known remedy "Protargol" in 295 solution (producer Istok-Plyus Ukraine), the droplet form pIrz//mmum.oroghemayiv.sot/peannLekKagzima/rgoiagdo!.pityapisieye-itekhi / vyBishShe--1) contains silver proteinate (agdepiy rgoyeipav). 2 g and auxiliary substances sodium phosphate, potassium dihydrogen phosphate, imidourea, purified water.

The well-known drug "Kolargol" (pirv:/Lumly.oroghemaieiI.sot/peinLekKagvima/koPagdo!. pit) contains in its composition up to 70 95 of colloidal silver and approximately 30 95 of albumin protein, which connects silver molecules together and supports them in active state, available in the following dosage forms: - solution for external use 0.2 o, 1 Uyu, 2 90; - powder (for preparing a solution); - ointment 15 9o; - eye drops 2 95, Z 90, 5 c.

However, these drugs contain many by-products, impurities, protein stabilizers and have a caustic effect that dries and injures the mucous membrane, and in a normal state it should be moist.

The useful model is based on the task of developing a barrier-prophylactic gel based on a colloidal silver solution obtained by electrolysis.

The task is solved in such a way that the barrier-prophylactic gel based on a colloidal silver solution contains as an active pharmaceutical ingredient a colloidal silver solution, as well as auxiliary substances, according to a useful model, a solution of colloidal silver with an activity of 45-55 ppt, obtained by the physical method of electrolysis , additionally contains bisabolol, D-Panthenol, lysozyme hydrochloride, thymol, zinc sulfate, vitamin

E, vitamin A, mint essential oil, auxiliary substances: glycerin, PEG-40, triglycerides, sodium hyaluronate, sodium/calcium alginate, dimethicone, propylene glycol, potassium sorbate, with the following ratio of components, (wt. 95): glycerin 5 ,0-20,0

PEG-40 hydrogenated castor oil 0.5-5.0 triglycerides 0.5-5.0 bisabolol 0.5-5.0

D-Panthenol 0.5-5.0 sodium hyaluronate 0.5-5.0 sodium/calcium alginate 0.5-5.0 dimethicone 0.5-5.0 propylene glycol 0.5-5.0 potassium sorbate 0. 01-1.0 lysozyme hydrochloride 0.01-1.0 thymol 0.01-1.0 zinc sulfate 0.01-1.0 vitamin A 0.01-1.0 vitamin E 0.01-1.0 ether peppermint oil 0.01-1.0 colloidal solution of silver 45-55 the rest. ppt

According to the utility model, the tool is presented in a tube with an applicator.

Colloidal silver is a product consisting of microscopic silver particles that form a suspension in demineralized and deionized water, obtained by the electrolytic method.

Colloidal silver has antiviral and antibacterial properties. Able to suppress the growth or cause the death of a wide range of bacteria, it has a virulicidal effect on the influenza virus and other viruses.

The bactericidal effect on Z(arpuyusossy5 acygei5) was noted at a concentration of colloidal silver nanoparticles of 45-50 ppm. Silver doses of 50-250 μg/l with long-term use are physiological and do not have a harmful effect on the body.

On Staphylococcus aureus, protea vulgaris, silver ions exert different antimicrobial effects - from bactericidal (the ability to kill microbes) to bacteriostatic (the ability to prevent the reproduction of microbes).

The mechanism of action of silver on viruses, bacteria, and fungi consists in inhibiting enzymes that control their energy metabolism.

Silver obtained by the method of electrolysis minimizes accompanying impurities and has a mild effect on the skin and mucous membranes. That is, silver obtained by electrolysis, the purest substance, which minimizes the presence of foreign impurities in the finished medical product.

Glycerin is a moisturizing and softening agent for increasing adhesion, adjusting the rheological parameters of viscous systems and their moisture-retaining properties. Helps improve skin permeability.

PEG-40 hydrogenated castor oil is a solubilizer (solvent) and stabilizer, viscosity modifier, restores the skin's natural moisture level, has a soothing effect on the skin, and is quickly absorbed.

Triglycerides are used as part of cosmetics and pharmaceuticals for oral, parenteral and local use. They are part of emulsions, microemulsions, self-emulsifying systems, solutions and suspensions as an emulsifier, solvent and suspending agent for API.

Bisabolol is an ingredient obtained from chamomile, an effective component that

Zo has the ability to relieve irritation of various origins on the skin. The most famous and valuable are its soothing, anti-inflammatory and antimicrobial properties.

D-Panthenol is used for moisturizing and accelerating the regeneration of various skin lesions as part of pharmaceutical and cosmetic products.

Sodium hyaluronate is found naturally in the vitreous body of the eye, serum, chicken combs, shark skin and whale cartilage. It is used as an adjuvant for the delivery of substances, a lubricant, a solution stabilizer.

Sodium/calcium alginate - a salt of alginic acid, which according to its chemical structure is a polyuronide consisting of sequentially connected residues of hexuronic acids, is used as an auxiliary substance. It exhibits gel-forming and bioadhesive properties, due to which it is widely used in the creation of products with hydrodynamic control of the release of active substances.

Dimethicone - in creams, lotions and decorative cosmetics, dimethicone is used externally (at a concentration of 10-30 90) to eliminate increased dryness of the skin and protect it from the irritating effects of the environment.

Propylene glycol is a diatomic alcohol of the aliphatic series, used in pharmacy as an auxiliary substance: a solvent for many water-insoluble AFfi; prevents drying of the aqueous phase in ointments, gels, o/w creams; softens the consistency of polymer films, promotes the absorption of many APIs. P. exhibits stabilizing and osmotic properties; has an antioxidant, preservative effect, prevents mold (5095 solution in aerosols is used for air disinfection).

Potassium sorbate - potassium salt of sorbic acid, is a natural preservative.

Lysozyme hydrochloride is an antibacterial agent, an enzyme of the class of hydrolases, a protein that is an enzyme that destroys the cell wall of bacteria due to the catalysis of the hydrolysis reaction of 1,4-beta bonds between the residues of M-acetylmuramic acid and M-acetyl-O-glucosamine in composition of the glycan chain of peptidoglycan and between M-acetyl-O-glucosamine residues in chitodextrin. Lysozyme is found in large quantities in many animal secretions, such as tears, saliva and mucus. Lysozyme is also found in cytoplasmic granules of polymorphonuclear neutrophils. This enzyme is also present in large quantities in egg whites. It is also used as a preservative in the food industry.

Thymol has antimicrobial properties.

Zinc sulfate is a trace element that is part of enzymes that participate in various biochemical reactions and synthesis processes of some hormones (insulin, corticotropin, somatropin, gonadotropin). It plays an important role in protein synthesis, carbohydrate metabolism. It affects the growth and development of body cells, the work of the nervous system, and the functioning of the immune system. If necessary, to improve the state of immunity in the prevention of viral, fungal and protozoan infections, allergic conditions.

Vitamin A has many biochemically important functions in the human and animal body. Retinal is a component of rhodopsin - the main visual pigment. In the form of retinoic acid, it stimulates growth and development. Retinol is a structural component of cell membranes. Provides antioxidant protection of the body.

Vitamin E is a key factor in strong immunity and cell protection. Mint essential oil has an antispasmodic, anti-inflammatory, antimicrobial, soothing, wound-healing, toning, refreshing effect.

Silver obtained by electrolysis is the purest substance, which minimizes the presence of foreign impurities in the finished medical product. A wide spectrum of antimicrobial action of silver,

Due to the lack of resistance to it in most pathogenic microorganisms, its low toxicity contributes to its introduction into the formulation as an antimicrobial antiseptic agent. Nanotechnology makes it possible to reduce the price of silver-based drugs and make them available for the treatment of many infectious diseases.

Example 1. Research to determine the optimal concentration of colloidal silver solution.

Table 1 shows a comparison of the solution of colloidal silver obtained by electrolysis, which is used in a useful model, with the above-mentioned drugs "Protargol" and "Kolargol".

Table 1

Differences between colloidal silver and traditional silver preparations

Name - Chemical s Method for depositing ppt, g/l ny name of production | manufacturers one bottle

Protargol Proteinat | Silver Chemical Nitrate per 101 10000 silver 7.5-8.5 95, silver, ml 0.1-2 | ppt/l protein to protein G that | (10 g/l), in 100 95 hydrolyzate | is | per casein, 1 Fo- accounts of gelatin, | 20 95 per pure egg protein consumption of 0.75-0.85 g/l consistency - 200000 ppt/l oxidative (200 g/l), reducible in reactions account for pure silver 17 g/l

Kolargol Silver I | Silver Chemical- Nitrate on 101 20000 sodium 70 9, silver, ml 0.2- | ppt/l of salt hydroxide 0.3 g, | (20g/l), lysalbin sodium that is in the new and (caustic is | protalbinatr account), on the pure new protein silver acid hydrolyzate 14 g/l, casein, sodium salts | followed by gelatin, | 2-3 95 zo0b0Orrt/l egg lysalbinity (ZOg/l),), new and | oxidative protein in the reprotalbi-reductive account of new acids | reactions to pure silver 21g/l

Colloidal Silver -- Nanoparticles | Physical - silver for 10 | 50 ppt/l aqueous solution of silver - | electrolysis 999.9 Ml- (0.05 g/l) silver 50 water 00005 g | ), in the per rrt account (according to Kk! is | for a purely useful 0.005 95 | silver model) is 0.05 g/l

In order to determine the optimal concentration of the colloidal silver solution, studies of the effect of silver preparations with an activity of 20 ppt, 30 ppt, 40 ppt, 45 ppt, 50 ppt on test cultures were conducted:

Rzendotopaz ayegidipoz ATOSS 27/99 earnuiosossiv aigei5 ATOS 25923

Based on the research results, graphs were drawn (Fig. 1-4).

Extrapolation of the obtained results of the effectiveness of silver against staphylococcus and Pseudomonas aeruginosa allows to determine an approximate "lethal dose" for them. It is 45-50 for earnuiosossiv aigei5 ATOSS 25923 and 55-60 ppt for Rheidotopavh aegidipoz ATOS 27/99.

The same samples of colloidal silver solution with an activity of 20 ppt, 30 ppt, 40 ppt, 45 ppt, 50 ppt were also tested on the test culture Sapaiida aiBisapz (Fig. 4). Yeast mushroom Sapaiida aibisapo completely stopped growing already at 20 ppt of colloidal silver.

That is, on the basis of the received empirical data, it is possible to determine the optimal activity of the colloidal silver solution, which should be used in the original formulation of the nasal spray based on the colloidal silver solution - 45-55 ppm.

The negative aspects of the use of antibiotic therapy listed above are an incentive to study alternative possibilities, one of which is phytotherapy.

Example 2.

The claimed medical product can be produced using standard equipment.

The process of preparing a medical product consists of the following stages: preparation for the production of colloidal silver by electrolysis, preparation of raw materials, during which the necessary amount of components is measured by weighing; preparation of the gel, in which the required amount of active substances is placed in the reactor according to the prescription; packaging of the gel in the required container, labeling and packaging, laboratory tests of each batch of the product.

The form of release is introduced for the first time, because barrier-prophylactic products in the form of a gel based on colloidal silver solution have not been produced before. The medical product is presented as a gel in a tube with an applicator, the status of which is defined by the Company as an invasive non-sterile medical product of the first class.

According to organoleptic and physico-chemical indicators, the medical product must meet the standards and requirements listed in Table 2.

Table 2 p/p with a yellowish tint 6. | Colloid stability 00 | Stable:/7//7/7/7/7/7777777ССсС 7. Mass fraction of water and volatile substances, 65-98.0

What

According to microbiological indicators, the medical product must meet the standards and requirements listed in Table 3.

Coo)

Table C of facultatively anaerobic microorganisms

According to the toxicological and hygienic, according to the received protocols, safety indicators, the medical product meets the standards and requirements listed in Table 4.

Table 4 p/p documentation 1 | index of acute toxicity and exposure to the skin (| ' 0

With | Index of sensitizing site -://СЇ17177111111110111111111сСс1С 4 | index of skin-irritating action /-://Ї7777777111101сСс1С (5 | Index of irritating action of the mucous membrane of the eye | 0

The total score of severity of irritation of the mucous membrane of the oral cavity and the mucous membrane in the area of the lip junction on the 1st-6th day of observation is 0 points.

The irritation factor is 0 points.

The severity of the irritating effect: absent.

The index of irritation on the mucous membrane of the oral cavity is 0 points.

Indications for use of the claimed drug are as a prophylactic barrier agent to protect the mucous membrane of the nose during an increase in the number of respiratory viral infections.

Example. WITH

Variants of the pharmaceutical composition are presented in Table 5.

Table 5

Composition of the drug to

The composition according to option 1 with a reduced amount of active substances has unsatisfactory pharmacological activity.

The composition according to option 2 corresponds to the qualitative and quantitative content of the components of the composition and has satisfactory pharmacological, physicochemical and technological characteristics.

The composition according to option 3 has unsatisfactory technological, physicochemical and pharmacological characteristics of the dosage form.

Thus, the new domestic drug being applied for is an effective medical product that belongs to pharmacy and refers to medical products that are used as a protective preventive barrier against the penetration of viral, bacterial infections and allergens on the nasal mucosa during the period of increasing numbers of respiratory viral infections

Claims (2)

USEFUL MODEL FORMULA 1. Barrier-prophylactic gel based on a colloidal silver solution, containing as an active pharmaceutical ingredient a colloidal silver solution, as well as auxiliary substances, which is distinguished by the fact that it contains a colloidal silver solution with an activity of 45-55 ppt, obtained by the physical method of electrolysis, additionally contains as active substances bisabolol, D-Panthenol, lysozyme hydrochloride, thymol, zinc sulfate, vitamin E, vitamin A, mint essential oil and auxiliary substances: glycerin, PEG-40, triglycerides, sodium hyaluronate, sodium/calcium alginate , dimethicone, propylene glycol, potassium sorbate, with the following ratio of components, wt. 9: glycerol 5.0-20.0 PEG-40 hydrogenated castor oil 0.5-5.0 triglycerides 0.5-5.0 bisabolol 0.5-5.0 D-panthenol 0.5-5.0 hyaluronate sodium 0.5-5.0 sodium/calcium alginate 0.5-5.0 dimethicone 0.5-5.0 propylene glycol 0.5-5.0 potassium sorbate 0.01-1.0 lysozyme hydrochloride 0.01- 1.0 thymol 0.01-1.0 zinc sulfate 0.01-1.0 vitamin A 0.01-1.0 vitamin E 0.01-1.0 mint essential oil 0.01-1.0 colloidal solution of silver 45-55 ppt the rest. 2. Barrier-prophylactic gel according to claim 1, which differs in that the product is presented in a tube with an applicator. Suppression to develop test cultures for the 20-th year of pollen growth. of contact PE Z o o o o o o o o o o o o Oso VO vo s s Z MYKHY EE UM IyII i KK HU PEK Zh sbrryaya ZbrrtAe heat AE Fort Ae AH Fig. 1 Bactericidal dose of silver in relation to co-sorous Aztecs (for 20 min; contact" between 45 and BOvot NKU "rent ethno ethnos tnee sten Esh i E zp VT5Ve Zhe VO pon m Va. Czech E e 1 pozh o n OM FOOOJO nn fr o 10 2O Zo a in BO and Bo Concentration of silver. dop t Pointer of careealation Fig. 2 Eactericidal dose of silver in relation to Rzentsotopaz vepldpova (for 20 ha. contayut) - between 55 and 60 rrt ep N U: what yu and them: Deshe p e nin pn v-vo tiche: t for us in p Y; EI; 20 Зо 40 5О в 7О 80 silver concentration, yy xx correlation index Fig. WITH Sapa aivisape eat OO o oo О555555:55555,55,,5,,,5,55,A I B Z MMK OO OO OOI B t OTHER ZVO AZOV I OKO OO o: ZU what E va. ss button 5 shi De menya С in . 5 ve sh M donu what ge ek 5 E nn TlTlTlTtnTttchtTchtchtnchtch t members of ВХ s a and Ba minus ka ve py to what they 85 OO A OA in o SN SHI a0000NNN E MOM MM a I M o pk shi ny a 8 then 185 of 35 of ZE Prema, time