Doctor rustamov's ointment

FIELD: medicine.

SUBSTANCE: ointment consists of emulsion base and pharmacologically active substance. The pharmacologically active substance of the ointment is presented by a fraction having a boiling temperature of 170-215°C (5-6 mm Hg) prepared by yolk pyrolysis on montmorillonite clay at 250-280°C for 20-30 min. The ointment also contains Carbomer, monoglycerides, hydrogenated coconut oil, glycerol, stearic acid, liquid paraffin, ethanol, myristyl myristate, hydrogenated lanolin, butylene glycol, polydimethyl siloxane, dimethicone, Nipagin, Nipasol, and a flavouring agent in certain proportions.

EFFECT: improving wound-healing action.

1 dwg, 1 tbl, 3 ex

 

The invention relates to the field of medicine, to new medicines in the form of soft medicinal forms (ointments for external use, which have a healing effect and can be used to treat wounds, ulcers, burns and other dermatological diseases.

Modern requirements for wound healing medicines the high and diverse. Wound healing ointments must have an active political action, prolonged osmotic activity, antibacterial properties. These ointments should be aimed at slowing the drying of the wound surface, to stimulate the growth of granulation, contributing to the formation of the epithelium. Arsenal wound healing ointments used in clinical practice, includes soft medicinal forms hydrophilic or fat base, containing a pharmacologically active ingredients of numerous inorganic, synthetic and natural organic compounds.

In particular, the known wound healing ointment on piaristengasse fat base, containing a pharmacologically active substances, salts of lanthanides in the amount of 1.5 to 2.5 wt.% [Pat. Of the Russian Federation No. 2141820 (1999) // the Ointment "Apaven" (IPC AC 9/06, AK 31/255)]. However, long-term consequences of the use of such high doses of heavy metals on laduma mutagenic and carcinogenic properties, studied were not.

In recent years, developers of new wound healing drugs are increasingly focused on natural compounds and their by-products, especially medicinal plant extracts and biologically active substances of animal origin. For example, it is known healing agent in the form of ointments containing humates and extract of Siberian ginseng, providing shorter wound healing in farm animals [RF Patent №2235548 (2003) // Wound healing agent (IPC AC 35/10, AK 35/78, AK 31/715, OR 41/00)].

The most widely used healing products containing the active ingredients of the herbal raw materials. In particular, the known emulsion ointment on the basis of the extract Oxytropis platanoides [RF Patent №2132692 (1999) // Dermatological, anti-inflammatory, wound healing and obezbolivaushee ointment "Exfil" (AC 35/78, AK 9/06)], superior to models of linear wounds, according to the authors of the invention, anti-inflammatory and wound healing activity of ointments "Flutsinar", "Lorenzen", "Solcoseryl" and "Marigold". Also known wound healing ointment containing solution rivanol, extract of Siberian ginseng, and infusion of yarrow, which has strong wound-healing, anti-inflammatory, immunomodulatory, antibacterial and obtb is counteracted by the action of the [Patent RF №2355411 (2009) // Healing ointment (IPC AC 36/28, AC 36/254, AK 9/06, OR 17/02].

It is known the use of bee products in the composition of wound healing agents, in particular, described the ointment "Polydoxy"containing phenolic compounds of propolis and lidocaine [Tikhonov A.I., popular this YEAR, Chernykh V.P. Theory and practice of production of medicinal preparations of propolis / Ed. by Acad. A.I. Tikhonov. - Kharkiv: the Foundation, 1998. - 384 p]. However, despite the large variety of proposed methods and medications, the problem of the treatment of wounds is still relevant, especially for pediatric and geriatric practice.

The aim of the invention is to develop a new healing tools in the form of soft medicinal forms for external use, with enhanced wound healing activity.

The invention consists in the use as pharmacologically active component of wound healing ointment pyrolysis products of egg yolk on montmorillonite clay in the following ratio of components, wt.%:

Water15
Carbomer15
Distilled monoglycerides15
Hydrogenated coconut oil is 10
Glycerin8
Stearic acid8
Paraffin liquid7,5
Ethyl alcohol5
Myristoleate4
Hydrogenated lanolin4
Butyleneglycol3
The polydimethylsiloxane2
The products of pyrolysis of egg yolk on montmorillonite clay2
Dimethicone1
Nipagin0,2
Nipazol0,2
Perfume0,1

Montmorillonite clay, produced in Azerbaijan, and its Russian equivalent bentonite contain as the main component of the aluminosilicate composition of Al2[Si4O10](OH)2·nH2O (montmorillonite), which made the focus of an inorganic polymer with a leaf-expanding structural cell due to which he has a very high swelling properties and capable of forming a gel-like structure. When the mixture of montmorillonite clay with egg yolks is its swelling, resulting in the formation of inorganic clusters ("nanoreactors"), filled with water and organic compounds that form the basis of egg yolk - mainly proteins and fats. Subsequent pyrolysis of the resulting material flows without contact with oxygen and is not accompanied by oxidation. Formed in this connection, according to the spectral studies, are low molecular weight products of the interaction of amino acids, short and cyclic oligopeptides with fatty acids, which are distilled in vacuo without further decomposition. Their use in the composition of the proposed wound healing ointments based on the emulsion provides the necessary therapeutic effect.

The following examples illustrate the invention.

Example 1. The receipt of the products of pyrolysis.

Well mixed mixture of 90 g of egg yolk and 30 g of montmorillonite clay is heated in a sealed steel vessel at a temperature of 250-280°C for 20-30 min, cooled and filtered. The filtrate is distilled in vacuum, allocating a fraction with So Kip. 170-215°C (5-6 mm Hg), the output 18-25 g, which at room temperature is still in the form of a waxy yellow-brown substance with a specific smell.

Range of IR were recorded on a FTIR spectrometer FSM-1201 in the tablet of potassium bromide. NMR spectra were recorded on a spectrometer Bruker AMXIII-400 in solutions of chloroform-D and DMSO-D6internal standard tetramethylsilane was.

In the spectrum of the IR-pyrolysis products are observed distinct absorption lines with highs in the field 2922 and 2852 cm-1(stretching vibrations of aliphatic C-H), 1705 cm-1(stretching vibrations of the carbonyl group C=O of unsaturated fatty acids) and 1636 cm-1(stretching vibrations of the carbonyl group C=O secondary amides).

An NMR spectrum1H, δ, ppm: 0.83 t (6 Hz, 10 H); 1,16-1,28 m (65 N); 1,47 t (6 Hz, 6 H), 1,85-1,90 m (4H); 2,14 t (8 Hz, 5 H); 5,20-5.35 m (2 N); 11,90 OSS (1 N).

The NMR spectrum1N is dominated by the signals of the protons of aliphatic fragments - terminal metal groups (0,83 ppm) and polymethene chain fatty acids and amino acids (1,16 of 1.28 ppm), the signals of protons in the alpha position to the carbonyl groups of fatty acids (1,85-1,90 ppm) and amino acids (2,14 ppm), no signals fragments of aromatic and heterocyclic amino acids (phenylalanine, tyrosine, tryptophan, histidine), observed signals unsaturated (5,20 to 5.35 ppm) and secondary amide (11,90 ppm) fragments.

An NMR spectrum13S, δ, ppm: 14,06; 22,47; 26,94; 29,17; 29,41; 29,52; 31,72; 33,95; 129,72; 130,18; 174,55.

An NMR spectrum13To confirm the presence of carbonyl groups and odnogo type (174,55 ppm), double C=C bonds (129,72 and 130,18 ppm) and complex chemical structure of aliphatic fragments (14,06-33,95 ppm).

Example 2. Manufacturing technology ointment.

In the calculated amount of water (15 g) is added 15 g of carbomer. Separately melt 15 g of distilled monoglycerides, 8 g of stearic acid, 4 g of hydrogenated lanolin and 4 g of maritimerelated. After melting, add 8 g of glycerol, 7.5 g of liquid paraffin and mix. Cooled to a temperature of 45-50°C, add 2 g of polydimethylsiloxane and 1 g of Dimethicone and get the hydrophobic fraction. 5 g of ethyl alcohol was dissolved 2 g of pyrolysis products of egg yolk and 3 g of butyleneglycol. To the resulting solution add 0.2 g of nipagin, 0.2 g nipazola and 0.1 g of odorants. After stirring 10 g of hydrogenated coconut oil and the previously obtained solution carbomer in water, mix. Add hydrophobic fraction, stirred until complete homogenization and get 100 grams of wound healing ointment proposed structure.

Example 3. Study of wound-healing action.

The experiments were performed on 30 rats male Wistar derived from kennel laboratory animals RAMS "Pillar" (Moscow region). The animals were kept in standard vivarium conditions, in accordance with GLP in preclinical studies in Russia [GOST C 51000.396 and 51000.496] international recommendations for the protection of vertebrate animals. Animals were divided into following groups: (Wound + Ointment) is a group of animals with simulated planar wounds, which caused the study ointment 1 time per day (Wound + Base) - the group of animals with a planar wounds, which were inflicted materials, not containing pyrolysis products of albumin, 1 time per day. The control group of animals (Control) wounds were not treated. Simulated planar wounds in anesthetized animals at pre-depilitory the skin of the back in the interscapular area special stencil with a scalpel by excision of skin the size of 20×30 mm [Methodical recommendations on experimental (preclinical) study of drugs for local treatment of purulent wounds // Moscow, 1989. - 48]. Size of the wound was measured by the gravimetric method, which consisted in the following. In advance on the torsion balance was determined by the weight of 1 cm2onion skin. To measure the area of the wound at last put the washed x-ray film and on the reverse side tracing felt the contours of the wound. The resulting image transferred onto tracing paper, then cut out the outline of the wound and weighed. The weight divided by the weight of 1 cm2onion skin. 3, 7, 14 and 21 days was measuring the area of the wound and calculated the percentage decrease wound for every 7 days compared to control. The results presented is ENES in table 1.

Table 1
Wound healing effect of the ointment containing pyrolysis products and egg yolks
№ p/pThe group of animalsThe average size of the wound, mm2(percent change compared to control)
3 dayday 714 day21 days
1Wound + Ointment385,3±18,2318,0±16,7*46,5±1,5*30,1±2,2**
-(-17,4)(-87,9)(-92,2)
N=10N=8N=5N=5
2Wound + Foundation394,7±18,3363,2±29,077,4±7,55*56,9±8,24*
-(vs.-7.9bn)(-80,3)(-86,8)
N=10N=6N=5N=4
3Control379,4±17,8363,4±18,1112,7±10,379,5±8,1
----
N=10N=6N=5N=4
Note: * - statistically significant differences from control: p<0,05 (rank univariate analysis the Kruskal-Wallis criterion Newman-Kalsa); N is the number of surviving animals.

Healing planar wounds in animals, which was applied daily ointment, optionally containing pyrolysis products and egg yolks, was much faster, which is especially noticeable at 14 and 21 days of treatment in comparison with the dynamics of wound healing actions in animals of group 2 (base ointment without pyrolysis products egg yolk) and group 3 (control) (figure 1). The number of surviving animals to to the NCU experiment was also higher than in the comparison group.

Thus, the ointment of the proposed composition has a pronounced healing effect, significantly speeding up the repair and scarring of the wound gap.

Ointment that has wound healing properties, consisting of the basics of emulsion type and pharmacologically active substances, characterized by the fact that as pharmacologically active substances it contains a fraction with So Kip. 170-215°C (5-6 mm Hg)obtained by pyrolysis of egg yolk on montmorillonite clay at a temperature of 250-280°C for 20-30 min, with the following ratio of components, wt.%:

Water15
Carbomer15
Distilled monoglycerides15
Hydrogenated coconut oil10
Glycerin8
Stearic acid8
Paraffin liquid7,5
Ethyl alcohol5
Myristoleate4
Hydrogenated lanolin4
Butyleneglycol3
The polydimethylsiloxane2
The products of pyrolysis of egg yolk on montmorillonite clay2
Dimethicone1
Nipagin0,2
Nipazol0,2
Perfume0,1



 

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