UA121953C2 - NOSAL SPRAY BASED ON A SOLUTION OF COLLOID SILVER WITH CYCLAMEN EXTRACT - Google Patents

Abstract

Nasal spray based on a solution of colloidal silver with cyclamen extract, containing as active pharmaceutical ingredient colloidal silver solution, as well as excipients, a solution of colloidal silver with an activity of 45-55 ppm obtained by physical electrolysis, further containing the active substance cyclamen extract, D-pan as excipients contains PEG-40 hydrogenated castor oil, rutin, essential oils of peppermint, ginger, eucalyptus, tea tree, camphor, vitamin E, potassium sorbate, thymol.

Description

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Fig.1

The invention belongs to pharmacy and relates to medical products that are used as an auxiliary means to relieve the course of runny nose accompanying rhinitis, frontitis, sinusitis, as well as to facilitate nasal breathing by thinning thick secretions and restoring the mucous membrane of the nose.

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 adjunctive therapy in 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 combined medical products that would act as to stop the development of infection in the nose, as well as to remove unwanted symptoms at the same time. Today, viruses and bacteria pose a serious threat to medicine and society, and are one of the main causes of morbidity and mortality in the population. Despite the successes in the development of drugs for antiviral, fungicidal and antibacterial therapy, modern treatment regimens are not able to fully control the course of infections: therefore, there is a need to create new effective drugs.

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.

A wide spectrum of antimicrobial action of silver, lack of resistance to it in most pathogenic microorganisms, low toxicity, as well as good tolerability contributed

Due 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 medicine in the form of a spray for the emergency prevention of acute respiratory viral infections (pat. RF Mo 2665959 publ.) contains sodium chloride and sodium hypochlorite solution with a pH equal to 8.0-10.0, an active chlorine concentration of 0.30-0, 60 mg/l and droplet size 90-110 μm.

The well-known remedy "Protargol" in 295 solution (producer Istok-Plus Ukraine), drop form (pIrz/Lumly.oroghemayiv.sot/peannLekKagvima/rgoiagodo!.pitzhapisie-iehi 5yBiShe-1) contains silver proteinate (agdepiy rgoieipeye) 2 g, and auxiliary substances sodium phosphate, potassium dihydrogen phosphate, imidourea, purified water.

The well-known drug "Collargol" (PpErv/Lumly.oroghemaieI.sot/peinLekKagwima/Koiiagdo!. pit) contains in its composition up to 7095 colloidal silver and approximately 3095 albumin protein, which connects silver molecules together and maintains them in an active state. available in the following dosage forms: - solution for external use 0.295, 195, 290; - powder (for preparing a solution); - ointment 1590; - eye drops 2905, 390, 590.

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 well-known drug "Synuforte" (pEerz:/LabieiKki.na/95rovAtTrovvyrovoryavot vto r1i1uvv849500956ВЕ90019580950190829560009585), which contains the active substances - extract and juice of European cyclamen.

But it is not used for rhinitis of allergic origin, cystic-polyposis rhinosinusitis, hypertension of the 2nd and 1st degree, in the treatment of children under 12 years of age.

The invention is based on the task of developing a nasal spray based on a colloidal silver solution obtained by electrolysis with the addition of cyclamen extract as an active substance

The task is solved in such a way that a nasal spray based on a solution of colloidal silver with cyclamen extract, containing as an active pharmaceutical ingredient a colloidal silver solution, as well as auxiliary substances, according to the invention, a solution of colloidal silver with an activity of 45-55 ppm obtained by the physical method of electrolysis, additionally contains the active substance cyclamen extract, D-panthenol, as auxiliary substances it contains PEG-40 hydrogenated castor oil, rutin, essential oils of peppermint, ginger, eucalyptus, tea tree, camphor, vitamin E, potassium sorbate, thymol in the following ratio components, wt. 9 Uyu: cyclamen extract 15-50

PEG-40 hydrogenated castor oil 0.25-3.0 rutin 0.25-3.0

D-panthenol 0.25-3.0 peppermint essential oil 0.25-3.0 ginger essential oil 0.25-3.0 eucalyptus essential oil 0.05-0.5 tea tree essential oil 0.05- 0.5 camphor 0.05-0.5 vitamin E 0.05-0.5 potassium sorbate 0.03-0.25 thymol 0.03-0.25 colloidal silver solution the rest.

Colloidal silver - a product consisting of microscopic silver particles that form a suspension in demineralized and deionized water, is 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 iarpuiyusossy5 ashtsygei5 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.

Cyclamen tubers contain a biologically active substance from the saponin group - cyclamine, which, when in contact with the mucous membrane, causes an irritating effect and causes increased reflex secretion, contributes to the natural cleansing of the nasal sinuses.

Cyclamen tuber extract is a folk remedy that has long been used for the treatment of sinusitis, frontitis, rhinitis, and ethmoiditis. Biologically active substances that are part of the plant cause intense reflex secretion in the mucous membrane of the nasal cavity, relieve swelling, show a local anti-inflammatory effect due to immunocorrective properties, which provides a quick and stable relief of symptoms that are characteristic of diseases accompanied by the formation of a thick secretion at acute respiratory diseases, sinusitis, frontitis, normalizes the body's immune response. Cyclamen contains a biologically active substance from the group of saponins - cyclamine, which when in contact with the mucous membrane causes an irritating effect and causes increased reflex secretion, contributes to the natural cleansing of the nasal sinuses.

Thus, in modern studies conducted using laser Doppler flowmetry, it was found that the extract of cyclamen tubers improves blood microcirculation in the mucous membranes of the nasal cavity.

According to the results of an experimental morphological study of the mechanisms of action of cyclamen extract, its multifaceted effect on the epithelial and stromal structures of the mucous membrane of the nasal cavity and maxillary sinuses was demonstrated: reflex synchronized secretion of glands, stimulation of local lymph and blood circulation, mucociliary transport, as well as local specific and non-specific immunity.

Research using contact endoscopy also made it possible to reveal improvement in the morphological and functional parameters of the mucous membrane of the nasal cavity.

Thus, the results of research in recent years indicate that phytotherapy, namely cyclamen extract, can become a real alternative to antibiotic therapy, reduce the number of antibiotics prescribed and prevent excessive and unreasonable use in the treatment of rhinosinusitis.

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

Mint essential oil has antispasmodic, anti-inflammatory, antimicrobial, soothing, wound-healing, tonic, refreshing properties.

Ginger essential oil has an anti-inflammatory and antiseptic effect.

Eucalyptus essential oil has pronounced anti-inflammatory activity, promotes rapid healing of wounds, exhibits analgesic, weak sedative, minor expectorant activity and has a tonic effect.

Tea tree essential oil has antibacterial, antiviral, antifungal properties, and also relieves swelling, itching, and inflammation.

D-panthenol is used to moisturize and accelerate the regeneration of various skin lesions as part of pharmaceutical and cosmetic products.

Vitamin E is a key factor in strong immunity and cell protection.

Camphor when used locally has an antiseptic, local irritant, analgesic and anti-inflammatory effect. Exciting the sensitive nerve endings of the skin, it reflexively improves the trophism of organs and tissues.

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

Rutin is used for prevention and treatment of avitaminosis P, in diseases accompanied by increased vascular permeability. In addition, P exhibits radioprotective, antioxidant, antispasmodic, wound-healing, antidote, antiallergic, anti-inflammatory, antiviral effects

Thymol has antimicrobial properties.

A local anti-edematous effect due to significant dehydration of the mucous membrane after using the product is noted. Colloidal silver solution and natural essential oils: tea tree, ginger, eucalyptus and mint have pronounced antiseptic, antifungal and bactericidal effects.

D-panthenol and vitamin E contribute to the regeneration of mucous membranes, improve nutrition, have a pronounced anti-inflammatory, moisturizing and soothing effect.

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 the electrolysis method, which is used in the invention, with the above-mentioned preparations "Protargol" and "Collargol".

Table 1

Differences between colloidal silver and traditional silver preparations - silver production is produced in vials of 10,000 rrit/l (10 and 5 silver nitrate, g/l), in terms of

Protargol Silver proteinate Silver 7.5-8.596, and hydrolyzate contains silver 0.75-0.85 g/l protein up to 10095 | sequence of casein, 1925-2092 - 200000 ppt/l of oxidized gelatin, - - (200 g/l), pure silver 17g/l in reactions

Silver nitrate, per 10 ml 20,000 rrit/l; svi With that

Silver " sodium (acidic sodium), which is converted to

Kolargol of pisalbin salt | that and and and protein makes up | pure silver 14 g/l protalbinic sodium salt sequence hydrolyzate 30000 rrit/l (30

SHIE slots of protalbin reducing gelatin, on pure silver 21 acids of reactions of egg white g/l

Colloidal solution 50 ppt/l (0.05 g/l), silver solution Silver in water Nanoparticles Physical silver 999.9 "which in terms of ppt (according to silver - electrolysis water is pure silver of the invention) 0.005 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:

Rzeidotopazh aegidipoza ATOSS 27/99 earnuiosossiv aigei5 ATOS 25923

Graphs were drawn based on the research results (Fig. 1-Fig. 6)

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 ziarpuiosossi5 aigei5 ATSS 25923 and 55-60 ppt for Rheidotopavh aegidiposa ATSS 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 a!irisapz (Fig. 4). The rain mushroom Sapaiida aibisape5 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 ppt.

Example 2. Study of the effect of cyclamen on gram-positive and gram-negative bacteria.

In order to determine the effectiveness of cyclamen, studies of the effect of cyclamen on test cultures were conducted:

Resepdotopaz ayegidipoz ATOSS 27/99 eiarpuiosossyv ashteiv ATOSS 25923

Significant losses of crop biomass are visible after 5 minutes of contact (Fig. 5).

Example 3.

The claimed medicinal product can be obtained using standard equipment.

The process of preparing a medical product consists of the following stages: production preparation, during which the required amount of components is measured by weighing; preparation of the solution, in which the required amount of active substances is placed in the reactor according to the prescription; filling of the solution into the required container, labeling and packaging, laboratory tests of each batch of the product.

The release form is introduced for the first time, because preparations based on silver and cyclamen have not been produced before, the spray is presented as a medical product in the form of a nasal spray in a dark plastic bottle with a spray pump, the status of which is determined by the Company as an invasive non-sterile medical product of the I class.

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

Table 2 shade 06. (|Colloid stability./////777777717171117111111111111 Stable./7/77/7/://фШС(ОС

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

Table Z of anaerobic microorganisms

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

Table 4

The norm according to

Mo n/p Indicator by regulatory documentation 1 (Index of acute toxicity when applied to the skin.d ОЙ ////7701111сСс21 2 |Index of chronic toxicity when applied to the skin.d////Y //07777сСс21

C (MIndex of sensitizing action /-/-:1Ї11111111101111сСс1С 4 (MIndex of skin-irritating action 77777111 6 (Index of acute toxicity and stomach lining) //:///|Ї 71011111

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-7th 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.

The indicated indications for use of the drug are a medical product that is used as an adjunct in the case of a runny nose accompanying adenoiditis, rhinitis, and rhinosinusitis.

Example 4.

Variants of the pharmaceutical composition are presented in Table 5.

Table 5

The composition of the drug

Cyclamen PHO root extract.//-/://777777711Ї11111111Ї11111111Ї1111

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 facilitates the relief of the runny nose accompanying rhinitis, frontitis, sinusitis due to the main expected effect on the nasal mucosa, without the help of pharmacological, immunological and metabolic means, but with the possibility promoting their functioning.

Claims (1)

FORMULA OF THE INVENTION Nasal spray based on colloidal silver solution with cyclamen extract, containing colloidal silver solution as an active pharmaceutical ingredient, as well as auxiliary substances, which is distinguished by the fact that the colloidal silver solution with an activity of 45-55 ppt is obtained by the physical method of electrolysis, additionally contains an active substance cyclamen extract, D-panthenol, as auxiliary substances contains PEG-40 hydrogenated castor oil, rutin, essential oils of peppermint, ginger, eucalyptus, tea tree, camphor, vitamin E, potassium sorbate, thymol in the following ratio of components, mass . 90: cyclamen extract 15-50 PEG-40 hydrogenated castor oil 0.25-3.0 rutin 0.25-3.0 D-panthenol 0.25-3.0 peppermint essential oil 0.25-3.0 ginger essential oil 0.25-3.0 eucalyptus essential oil 0.05-0.5 tea tree essential oil 0.05-0.5 camphor 0.05-0.5 vitamin E 0.05-0.5 potassium sorbate 0.03-0.25 thymol 0.03-0.25 colloidal silver solution the rest. Suppression of the development of taste cultures for the second hour of calf growth lO-min. contact 5 scha her o OO a Pkavtovtova vovi s s pozhinyn oo nan ten no KISTU OH zhOovrpAchCh bo rrvAye Or Ad aa rrtaya Zrrt vo Fig Bactericidal dose of silver in relation to Tarpuyusossisis aitenia (for 20 minutes of contact) - between 45 and BOROt VU dr nt ve ; : SO THAT O80 o Mer V Foma niiiipiippiippipipipipiiiipipicyshiiiiy it is Zo; и оно 5 вШ0-00Х о 10 2 Зо 40 50 о о о о о Silver concentration, pp x "correlation index Fig. 2 bactericidal dose of silver in relation to Reeshiotopes of aetidipose (for 20 he. contact) - between 55 and 6О0 рр шов nn p -nshcmsh ma ia E ch VE 76 p an r nn CHYM, o t 20 Zo 40 50 bo 70 o Silver concentration , horns "- correlation indicator Fig. WITH Sapatsia yabisape 12 PKT a sho. 1 OM s U von, yana: BONN KO byaYannnnnnnn M mus Ann BO dn dn nd Y 5 in her 20 25 Za Zb Vremy, time Fig. 4 Suppression of the development of test cultures for b hour of growth in after 20 min of contact - "sho NBNBNNN NN NN NN nn nn o VO 5. av her s Shan i ZO s Esh o. oh oh o s s o I: 5 p o. | о и i hortAF For rotAc 4brrotAd Cyclamenos 0 50 rota spray Fig. 5 Growth accounting P8. aegidipoga for b hour sho che shchi sho shsh Ш BO MO UOO OKO OO a MY 58 o o o OO s o E o 1 o o o . at. 1 o. o Z 4 Z MO praparatev: Z - 39 years, 4 - 50 years, 5 - Cyklamenos Shbhv. LOhv. C2 obhv Fig. 6