RU2629330C1 - Means for nasal application - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: means contains sea-buckthorn oil or 15% propolis oil extract in an amount of 10 wt % and sodium thiosulfate in an amount of 10 wt % as active ingredients, and vaseline in an amount of 20 wt %, T-2 emulsifier in an amount of 10 wt %, F-68 lutrol in an amount of 10 wt %, RH-40 cremophor in an amount of 8 wt %, chitosan in an amount of 2 wt % as an ointment base, and purified water.

EFFECT: invention expands the arsenal of means in the form of nasal ointments that have an anti-inflammatory and wound-healing effect with the effect of prolongation.

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Description

The present invention relates to medicine, namely to pharmacy, and for the development of ointments for the complex treatment of rhinitis, tonsillitis, sinusitis.

Known nasal drug "Morenazole", made in the form of a spray and containing the active and auxiliary substance, natural minerals and trace elements, in which the natural sea salt is used as the active substance, water for injection is used as the auxiliary substance, and the isotonic sterile solution has osmolality from 220 to 350 mmol / kg of water and a pH of from 6.0 to 9.5 and contains sodium, magnesium, calcium, potassium, hydrocarbon ions [Patent RU 2369397, 2009].

A known composition for nasal use containing active and auxiliary substances, in which the sea salt and alpha-glutamyl-tryptophan are used as active substances in the following ratio of active substances (wt.%): Sea salt 95.00-98.00; alpha-glutamyl-tryptophan 2.00-5.00, and the composition is made in the form of drops, spray or aerosol [Patent RU 2540496, 2015].

Dosage forms for nasal use are known which contain dexpanthenol in combination with a corticosteroid. Preferred dosage forms are ointments, sprays, aerosols, solutions and suspensions. Preferred corticosteroid preparations are hydrocortisone, beclomethasone-17,21-dipropionate, as well as dexamethasone. The content of dexpanthenol is preferably in the range from 0.5 to 20% wt., Especially from 5 to 15% wt. The proportion of corticosteroid preparation preferably lies in the range from 0.01 to 10% wt., Especially from 0.01 to 5% wt. These dosage forms can be used, in particular, for the treatment of allergic skin diseases or allergic symptoms in the nose [http://www.findpatent.ru/patent/247/2472499.html].

Known antiviral agent based on recombinant interferon in the form of an ointment, gel, suppository, cream, liniment containing a consistent-forming base with the addition of nipagin and polyvinylpyrrolidone, as well as Trilon B, butyloxytoluene, dimethyl sulfoxide and tween-80 [patent RU 2129].

Known means in the form of a gel or ointment for external use, with antiherpetic activity, wound healing and antiviral action, which contains hyaluronic acid, trimecaine, glycerin and polyethylene oxide [patent RU 2178693, 2002].

Known antiviral agent in the form of a gel containing human leukocyte interferon, as a basis 2% solution of a copolymer of styrene and maleic anhydride, nipagin [patent RU 2302881, 2007].

Known external agent for the treatment of diseases of the skin and mucous membranes caused by the herpes simplex virus, containing as active ingredient the peptide SEQ ID NO: 1 (allostatin-1), and as auxiliary substances glycerin, allantoin, urea, triethanolamine, carbopol At 21, kemaben [patent RU 2338553, 2008].

Known immunocorrective agent for the treatment of diseases of viral etiology, which contains interferon human recombinant alpha, and / or beta, and / or gamma antioxidant complex of tocopherol acetate or its derivatives, including water-soluble, and salts of ascorbic acid, calcium pantothenate, antiviral components, as well as auxiliary and formative components at certain ratios per 1 g of the drug, while the tool includes arbidol and its components as antiviral components derivatives, rimantadine, oseltamivir, ribavirin, inosine pranobex (isoprinosine), glycyrrhizic acid and its derivatives, nucleosides from the series - famvir, valacyclovir, ganciclovir, valganciclovir, foscarnet, cidofovir, lobucavir, sirivirudinovidin, liruvirdin-birudinovidin, stavudine. The tool is made in the form of rectal-vaginal suppositories, gel, ointment, liquid [patent RU 2411039, 2011]. The invention provides a high therapeutic effect and a high degree of bioavailability.

Known oxolinic ointment is a synthetic preparation, the active substance is oxolin (1,2,3,4-tetrahydro-1,2,3,4-tetraoxynaphthalene dihydrate). Available: 0.25% oxolinic ointment, in tubes of 10 g; 0.50%, 1%, 2% and 3% oxolinic ointment, in tubes of 10 g, 30 g and 50 g. Influenza and the prevention of influenza. Viral diseases of the skin and eyes: viral rhinitis, keratoconjunctivitis, keratitis, herpes simplex and herpes zoster, genital warts, warts, molluscum contagiosum [http://www.citopsor.com/index.php?option=com_content&task=view&id=117; http://www.piluli.ru/product/Oksolinovaya_maz]. This drug has an antimicrobial, bacteriostatic effect, is used in therapy for the prevention and treatment of acute respiratory viral infections, however, the absorption of the drug with external use is insignificant, the drug has no anti-inflammatory and prolonged action.

The closest analogue of the invention is the nasal ointment Evamenol, used as a symptomatic agent in the treatment of acute and chronic rhinitis, containing L-Menthol 1 g; eucalyptus oil 1 g; Vaseline up to 100 g [Evamenol® [Electronic resource] Access mode: http://mosfarma.ru/katalog/bezrecepturnye/ot-prostudy-i-grippa/evamenol. Access date: 06/09/2016].

The objective of the invention is the expansion of the arsenal of funds in the form of nasal ointments with anti-inflammatory and wound healing effects, with the effect of prolongation.

EFFECT: obtaining a new medicinal product of nasal administration in the form of an ointment, which has anti-inflammatory and wound healing effects, which provides the maximum intake of active substances for external use, with a prolongation effect.

The specified technical result is achieved by the fact that the means for nasal use containing active ingredients and an ointment base including petrolatum, according to the invention, as active ingredients contains sea buckthorn oil or propolis oil extract 15%, sodium thiosulfate, and additionally contains an emulsifier T as an emulsion base -2, cremophor RH-40, lutrol F-68, chitosan and purified water in the following ratio of components, wt. %:

sea buckthorn oil or propolis oil extract 15% 10 sodium thiosulfate 10 petroleum jelly twenty emulsifier T-2 10 Lutrol F-68 10 cremophor RH-40 8 chitosan 2 purified water up to 100

In this case, the propolis oil extract contains vegetable oil as a solvent.

The invention is illustrated by the following tables: table 1 shows the kinetics of the degree of runoff (angle of inclination 45 °) of a nasal ointment in vitro; table 2 shows the kinetics of the degree of runoff (angle of inclination 90 °) in vitro nasal ointment; table 3 - determination of the antimicrobial activity of ointments with sea buckthorn oil and sodium thiosulfate; table 4 shows the antibacterial activity of a nasal ointment with propolis oil extract and sodium thiosulfate.

All components that make up the ointment are approved for medical use.

Sea-buckthorn oil P-8-242 No. 009143 02/17/97.

Purified water (FS 42-2619-97).

Lutrol F-127 (LutrolF-127), BASF (Germany) 9003-11-6 helps prolong the active ingredient in the composition.

Cremophor RH-40 (Cremofor® RH-40) BASF (Germany) No. 013635 / 01-2002 hydroxyethylated hydrogenated castor oil, improves the structure of the solvent, increases the bioavailability of the active ingredients introduced into the composition due to surface-active properties.

Propolis TU GOST 28886-90.

The emulsifier T-2 (TU 18-17-05-76) gives the mass sufficient elasticity, is used as a stabilizer, plasticizer and emulsifier.

Chitosan (TU 9289-003-49857769-2003) - “Crab chitosan” is a natural polymer - the film-forming agent chitosan, which is easily soluble in acetic acid with the formation of transparent viscous solutions, upon drying of which a strong film is obtained.

The introduction of sea buckthorn oil or propolis oil extract in combination with sodium thiosulfate stimulates tissue regeneration processes, promotes the manifestation of anti-inflammatory, reparative action, a combination of ointment base excipients provides a prolonged effect of the dosage form.

The introduction of a sea buckthorn oil or propolis oil extract into the drug composition increases the antimicrobial activity of the ointment due to the fact that the active substances have a wide spectrum of action against gram-negative and gram-positive microorganisms, in particular Staphylococcus spp. (strains producing and not producing penicillinase, as well as penicillin-resistant strains).

In addition to the manifestation of known properties, each component of the claimed composition in the aggregate enhances its effect, which is explained, obviously, by the effect of their synergism.

As a result of experimental studies, it was found that the emulsion base provides reliable fixation of the drug on the mucous surface when applied to the nasal mucosa, promotes a better distribution of sea buckthorn oil or propolis oil extract and sodium thiosulfate in the base, increases the bioavailability of active substances due to surface-active properties. Giving the drug the form of an ointment provides convenience and hygiene of use, the drug forms a non-slip film when applied to the mucous surface of the nose, has a pronounced prolonged effect and storage stability.

Example 1. Composition 100.0 ointments: sea buckthorn oil - 10; sodium thiosulfate - 10; petroleum jelly - 20; emulsifier T-2 - 10; cremophor RH40 - 8.0; Lutrol F-68 - 10.0; chitosan - 2.0; purified water to 100.0.

An ointment is prepared as follows. Emulsifier T-2 is fused in a water bath with petroleum jelly, cremophor. Lutrol is added to the alloy. The mixture is thoroughly mixed, purified water is added in portions, stirred with a stirrer until a homogeneous mass. Sea buckthorn oil and sodium thiosulfate are added to the ointment base at a temperature of 20 ° C as a suspension, and again mixed with a stirrer. The resulting ointment is homogeneous, of a satisfactory consistency, is easily distributed on the surface of the nasal mucosa, is stable, the density is 1.35 g / cm ³ , the pH of the ointment is 6.0.

The resulting ointment is easily applied to the mucous membranes of the nose with the formation of an even continuous smear, has a pronounced prolonged effect, as well as convenience and hygiene of use due to the proposed composition of the ingredients.

Example 2. Composition 100.0 ointments: sea buckthorn oil - 10.0; sodium thiosulfate - 10.0; low molecular weight polyethylene (NMPE) - 15.0; glycerin - 8.0; cremophor RH 40 - 1.0; Lutrol F-68 - 15.0; chitosan - 2.0; purified water to 100.0.

An ointment is made in a similar manner.

The obtained ointment has a thick and viscous consistency, there are inconveniences when applied to the nasal mucosa, the ointment is satisfactorily fixed, but is unsatisfactorily washed off the mucous surface, which is explained by the introduction of NMPE, there is discomfort when applied to the surface of the mucous membranes, the smear is uneven.

Example 3. Composition 100.0 ointments: sea buckthorn oil - 10.0; sodium thiosulfate - 10.0; petrolatum - 10.0; cremophor RH 40 - 1.0; chitosan - 1.0; purified water to 100.0.

An ointment is prepared as follows. The emulsifier T-2 is fused in a water bath with cremophor. The mixture is thoroughly mixed, then purified water is added in portions, mixed with a stirrer until smooth. Sea buckthorn oil and sodium thiosulfate are added to the ointment base at a temperature of 20 ° C as a suspension, and again mixed with a stirrer. The ointment obtained is homogeneous, of a satisfactory consistency, distributed on the surface of the nasal mucosa, is washed off unsatisfactorily, discomfort is noted when applied to the surface of the mucous membranes. The ointment is not plastic enough consistency.

Example 4. Composition 100.0 ointments: propolis oil extract 15% - 10; sodium thiosulfate - 10; petroleum jelly - 20; emulsifier T-2 - 10; cremophor RH 40 - 8.0; Lutrol F-68 - 10.0; chitosan - 2.0; purified water to 100.0.

An ointment is prepared as follows. Emulsifier T-2 is fused in a water bath with petroleum jelly, cremophor. Lutrol is added to the alloy. The mixture is thoroughly mixed, purified water is added in portions, stirred with a stirrer until a homogeneous mass. An oily propolis extract and sodium thiosulfate are added to the ointment base at a temperature of 20 ° C as a suspension, and again mixed with a stirrer. The resulting ointment is homogeneous, of a satisfactory consistency, is easily distributed on the surface of the nasal mucosa, is stable, the density is 1.35 g / cm ³ , the pH of the ointment is 6.0.

The resulting ointment is easily applied to the mucous membranes of the nose with the formation of an even continuous smear, has a pronounced prolonged effect, as well as convenience and hygiene of use due to the proposed composition of the ingredients.

From the above examples it is seen that the compositions described in examples 1 and 4 are optimal from the point of view of consistency, ease of use.

The determination of the antimicrobial activity of the claimed ointment was carried out according to the requirements for dosage forms, namely, the antibacterial properties of the developed composition of the ointment according to example 1 and the composition of the ointment according to example 4. Studies of the antibacterial effectiveness of the ointment were carried out according to the method described in the GF XII ed., OFS 42- 0068-07 (Table 1).

The proposed dosage form is an ointment containing sea buckthorn oil or propolis oil extract, sodium thiosulfate as active substances, is convenient to use and has a wide scope in ENT practice: complex treatment of infectious and inflammatory diseases of the nose. An otolaryngologist, depending on the form and severity of the disease, can recommend to patients for complex treatment the necessary amount of nasal ointment when applied to the mucous membranes of the nose for self-treatment, which makes the claimed ointment a promising dosage form in ENT practice.

Claims (3)

1. A means for nasal use containing active ingredients and an ointment base including petroleum jelly, characterized in that it contains buckthorn oil or propolis oil extract 15%, sodium thiosulfate as active ingredients, and additionally contains T-2 emulsifier as an emulsion base, cremophor RH-40, lutrol F-68, chitosan and purified water in the following ratio of components, wt.%: sea buckthorn oil or propolis oil extract 15% 10 sodium thiosulfate 10 petroleum jelly twenty emulsifier T-2 10 Lutrol F-68 10 cremophor RH-40 8 chitosan 2 purified water up to 100 2. The tool according to claim 1, characterized in that the propolis oil extract as a solvent contains vegetable oil.