RU2417086C1 - Agent for treating local allergic exudative-inflammatory and infiltrative-inflammatory skin processes - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to drugs, and concerns an agent for treating local allergic exudative-inflammatory and infiltrative-inflammatory skin processes, containing Elocom Lotion with mometasone furoate as a drug substance, differing by the fact that additionally its contains an aqueous solution of Furacilin in mass dilution of Furacilin: water as 1: 5000, in the following proportions, parts by volume: Elocom Lotion 1, aqueous solution of Furacilin 5.

EFFECT: extended range of products for treating local allergic exudative-inflammatory and infiltrative-inflammatory skin processes.

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Description

The invention relates to medicine, namely to medicines used in dermatology and having a multifactorial effect on local allergic exudative-inflammatory and proliferative inflammatory processes of the skin, accompanied by the presence of "soak". The invention can be applied in medical practice with inpatient and outpatient treatment.

To understand the essence of the issue, it should be pointed out that dermatological skin disease, accompanied by weeping, refers to the true (idiopathic) form of eczema and is characterized by rashes in the form of an island-inflammatory, edematous spot with the subsequent formation of many small vesicles on this background, which, without having time to form, quickly open . The opened vesicles leave behind a spot erosion, from which a serous oozing exudate is released. Gradually, the serous fluid dries up and crusts of a grayish-yellow color form. The process proceeds in waves, so all of the listed elements of the rash are present simultaneously, creating one of the most characteristic signs of eczema - evolutionary polymorphism, i.e. the presence of various types of rashes in one focus.

To treat this disease, dressings soaked with the drug are more often used. However, many drugs applied to the dressing in the form of solutions (hypertonic solution of sodium chloride, urea, furatsilina, dioxidine) dry out after 2-3 hours, are inactivated by wound exudate. That is why the local use of solutions of various antimicrobial agents is ineffective.

To prevent drying of the dressing, ointments, usually prepared on a fatty lanolin-vaseline basis, are widely used. Due to the weak diffusion of drugs from the fat base, the concentration of the drug in the tissues of the wound is small.

The second drawback of treatment under the dressing with the use of traditional drugs is that most of them have unidirectional effects: only osmotic (hypertonic solutions, one-component sorbents), only antibacterial (antibiotics, antiseptics) or, mainly, non-proliferative (enzymes).

The complex pathogenesis of the local allergic process that occurs with true atopic dermatitis, necessitates a multidirectional effect. But the range of topical drugs with pronounced exudative processes on the skin is limited, as creams and ointments are not recommended due to the effect of “warming up” and increasing infiltrative skin changes. Mainly used are drying antiseptic solutions (a solution of brilliant green, Castellani paint, Fucorcin, etc.) or shaken mixes (talkers) based on zinc or tannin, which do not have an antiseptic effect.

Given the above, the pharmaceutical market offers a large number of combination preparations containing both hormonal drugs and antibacterial and antifungal agents (Triderm, Akriderm-GK, celestoderm with garomycin). But they are all creams and ointments, and therefore are not recommended for wet dermatitis.

Allergic infiltrative-inflammatory and exudative-inflammatory skin lesions are characterized by a pronounced exudative process. Exudate is an excellent breeding ground for microbial flora, and therefore eczema, especially in children, is often accompanied by bacterial complications.

The drug Furacilin (reg. No. RK-LS-5 No. 007536 from 05.22.2003, the active substance is nitrofural) is a well-known antiseptic with a wide spectrum of action, which has not lost its effectiveness. The drug is used to treat and prevent purulent-inflammatory processes, wound infections and inside to treat bacterial dysentery. The use of furatsilin in the treatment of childhood and infant forms of allergic skin lesions is justified by the high risk of bacterial complications. However, allergic dermatitis has been identified as a side effect of furatsilin, i.e. its use for the treatment of weeping atopic dermatitis may be limited, especially in infancy.

From the patent of the Russian Federation No. 221409, publ. 2008, it is known a tool for the treatment of skin diseases with primary and secondary infection, which contains a glucocorticosteroid - mometasone furoate (Elokom), heparin, antimycotic and antibiotic. The specified tool does not develop secondary infection and sensitization to fungal and bacterial antigens.

However, its disadvantages include the fact that such complex preparations (hormone, antibiotics and an antifungal agent) are used only with strict indications and with caution in childhood (especially in infancy) with weeping dermatitis, since, firstly, they have an ointment base (in aqueous solutions, local topical antibiotics are not effective, can be destroyed by coccal flora enzymes and under the influence of changes in the acid-base state in the wound areas of the skin), and secondly, in case of violation of the integrity of the skin ova, the risk of a general systemic resorptive effect of both antibiotics, antimycotics, and hormones increases.

The closest to the proposed technical solution for the intended purpose is the drug Elok lotion, containing 1 ml of 1 mg of mometasone furoate, which has anti-inflammatory, antipruritic, antiexudative effect and is used to attenuate and eliminate inflammation and itching in dermatoses amenable to glucocorticoid therapy (Radar Encyclopedia medicines, 2009 17, Moscow “Radar-2009”, 2008, pp. 997-998).

However, basically this lotion is presented as a remedy for eczema of the scalp. In this case, Elok lotion due to suppression of local immune defense can cause the development of bacterial septic complications, which is especially dangerous for infants.

The technical result achieved by the proposed technical solution is to create a tool for the treatment of local allergic exudative-inflammatory and infiltrative-inflammatory processes of the skin while increasing the effectiveness of treatment by reducing the healing time, due to the leveling of side effects of each of the components included in the new tool, while ensuring versatility for various groups of patients, including patients of the infant from 1 month and childhood .

The specified technical result is achieved by the proposed tool for the treatment of local allergic exudative-inflammatory and infiltrative-inflammatory processes of the skin, containing Elok lotion with mometasone furoat as an active substance, characterized in that it additionally contains an aqueous solution of Furacilin with mass dilution of Furacilin: water as 1: 5000 , in the following ratio of components, about. h:

Elocom lotion one aqueous solution of furatsilin 5

The technical result is achieved due to the following.

As it turned out unexpectedly, the mixture of the proposed components with their stated ratio allowed not only to enhance the positive effects (synergistic effect), in particular to reduce the treatment time and the frequency of bacterial and allergic complications, but also to level the side effects of the used component preparations. With the combined use of Eloc lotion and an aqueous solution of Furacilin, we, on the one hand, prevent bacterial complications caused by both the accumulation of exudate and the use of a topical steroid (due to furatsilin), on the other hand, pathogenetically stop allergic inflammation (due to Eloc lotion), with the third, we prevent the development of allergic reactions to furatsilin (since in the annotation, allergic dermatitis is a side effect of furatsilin).

Apparently, the synergy of these effects is ensured also by the peculiarities of the physicochemical interaction of the active base with Elok lotion (mometasone furoate) and the active base Furatsilina (nitrofural) taken in a strictly defined ratio (established experimentally) and used as a wet-drying dressing . Due to its antiseptic properties, furatsilin destroys and inhibits the growth of the bacterial flora, reduces the formation of necrotic pathological proteins, including enzymes, which in turn inactivate mometasone furoate. In addition, the drying effect of Furacilin solution improves the access of topical hormones to the lesion. Dilution of Elok lotion with furatsilin solution reduces the dose of the active substance (mometasone furoate), which, along with a new mechanism of action, allows you to use the method of treatment with this tool even in infancy (from 1 month old).

The choice of Furatsilin solution as an aqueous solution in a dilution of 1: 5000 is due to the dissolving properties of furatsilin, as well as the presence of such a finished form in the form of an official aqueous solution. The volume ratio of the components in the proposed tool was established empirically, namely: with a decrease in the dose of Elokom, the effectiveness decreases significantly, and with an increase in its content, the number of bacterial complications in patients, especially in children, increases.

The proposed therapeutic agent was prepared and tested in an inpatient and outpatient setting. The following substances were used for its preparation:

- Elocom lotion (reg. No. P No. 013256 / 03-2001 of 08/01/2001, containing 1 mg 1 mg of mometasone furoate as active substance; excipients: 40% isopropyl alcohol; propylene glycol; hydroxypropyl cellulose; sodium phosphate; water. Maybe also contain phosphoric acid and sodium hydroxide to establish a pH value of approximately 4.5);

- Furacilin (reg. No. RK-LS-5 No. 007536 dated 05.22.2003, the active substance is nitrofural) is a well-known antiseptic with a wide spectrum of action. It is used to treat and prevent purulent-inflammatory processes, wound infections and inside for the treatment of bacterial dysentery;

- An aqueous solution of Furacilin can be used in the form of an official 1: 5000 aqueous solution or prepared independently using distilled sterile water.

The proposed tool is prepared as follows.

Example. First, an aqueous solution of Furacilin is prepared, for which 100 mg of solid Furacilin is mixed with 500 g of distilled sterile water at a temperature of 100 ° C, and an aqueous solution of Furacilin with a dilution of 1: 5000 is obtained. Then, the proposed therapeutic agent is prepared, for which 1 ml of Elok lotion (room temperature 22-23 ° C) is mixed with 5 ml of previously prepared aqueous solution of Furacilin at a solution temperature of 37 ° C (the temperature should be no more than 40 ° C, since at more high temperature decreases the active properties of the prepared product), shake for 15 seconds. The result is a therapeutic agent with the following ratio of components, ob.ch .: Elok lotion 1; aqueous solution of furatsilin 5.

The inventive tool was used in the treatment of 34 patients (the main group - O) aged 1 month to 56 years suffering from atopic dermatitis. To do this, take sterile gauze wipes (mainly 6 layers), moisten in a freshly prepared solution of the proposed product, squeeze it out slightly and apply to the affected area of the skin for 2 hours, while additionally moisten every 60 minutes. The procedure is carried out the first two days 2 times a day, in the following days 1 time a day until the disappearance of island-inflammatory changes on the skin. Comparison groups consisted of patients using either Elok lotion alone (26 people aged 6 months to 52 years old - C1), or only dressings with an aqueous solution of Furacilin dilution 1: 5000 (14 patients aged 1 month to 59 years old - C2) with the same treatment sequence. All studied groups were identical in age and sex composition and the degree of exacerbation of atopic dermatitis.

Efficiency was assessed by the area dynamics (according to SCORAD) of the severity of weeping, swelling, hyperemia, the degree of bacterial contamination of the skin (sowing from the focus of inflammation) on the 5th and 10th day of observation, and changes in ultrasonic blood flow in the skin around the affected areas. The data obtained during the studies are shown in tables 1 and 2.

A comparative evaluation of the results of clinical trials in the above three groups that are on various types of therapy (treatment using the proposed tool, isolated Elok lotion and aqueous solution of Furacilin), showed the following:

- in the main group (O) on the 3rd day of treatment, there was a clear positive dynamics in the form of the complete disappearance of weeping and edema, while maintaining slight hyperemia in 93% of patients (aged 1 month to 56 years), while in the groups comparisons (C1 and C2) even on the 5th day, relief of inflammatory skin changes was observed only in 68% and 18% of cases, respectively;

- the highest degree of elimination of the bacterial flora from the surface of the skin was recorded only in patients of the main group, and this indicator exceeded the same in both group C1 and C2 (results in the last column of table 1);

- the dynamics of intradermal and subcutaneous blood flow (data in Table 2) in the main group, evaluated by ultrasonic methods of research, indicated the elimination of venous stasis with a decrease in arterial filling, which contributed to a decrease in edema and an improvement in trophism of the affected tissues. In the comparison groups, changes in indicators were either statistically unreliable (for group C2) or indicated negative dynamics (for group C1).

In addition, treatment showed that not a single child from the main group developed side effects (even in infants), while 3 patients from group C2 (age 2 months, 1 year 7 months, 6 years) (21 , 4%) using an aqueous solution of Furacilin, a local allergic reaction was observed in the form of a small-papular rash around the lesion, in 4 children from group C1 (7 months, 1 year 4 months, 4.5 years) (15.4%) using applications Elokom lotion - accession of microbial and fungal flora.

Thus, the claimed formulation of the therapeutic agent allowed to increase the effectiveness of treatment by reducing the treatment time and increasing the success rate, leveling side effects inherent in its components separately, and ensuring universality for various groups of patients, including infants from 1 month. Along with the foregoing, the proposed tool allows you to expand the range of available medicinal compositions for the treatment of local allergic exudative-inflammatory and infiltrative inflammatory processes of the skin. The method of preparation of the claimed funds and the method of treatment it is simple and can be mastered in any clinic.

Table 1 Comparative evaluation of treatment effectiveness in examined patients with atopic dermatitis Patient groups Number of patients Efficiency (on day 10) (%) The proportion of patients with complete relief of the process (on the 5th day of treatment) (%) Bacteriological Results Furacilin (C2) fourteen 57.0 * 18.0 * Complete elimination of S.aureus in 59.0% of patients within 1 week, decreased colonization of S.aureus in 69.0% of patients Eloc Lotion (C1) 26 59.0 * 68.0 * Decreased colonization of S.aureus in 38.0% Furacilin + Elocom Lotion (O) 34 98.0 93.0 (on the 3rd day of treatment) Complete elimination of S.aureus in 79.0% of patients within 1 week, decreased colonization of S.aures in 85.0% of patients * significantly significant differences compared with "O"

table 2 Indices of intradermal and subcutaneous blood flow (cm / s) in patients with atonic dermatitis before and after treatment in the studied groups of patients (M ± s) Blood flow characteristics Furatsilin + Elokom lotion Furatsilin Elocom Lotion Before After R Before After R Before After R Inside skin Arterial Vmax 8.53 ± 2.46 0.002 ± 0.001 0.0032 9.16 ± 2.51 3.45 ± 1.98 0.46 7.85 ± 2.25 0.007 ± 0.001 0.006 Vmin 0.55 ± 0.27 0 0,000 0.76 ± 0.33 0.68 ± 0.41 0.34 0.77 ± 0.18 0 0,000 IR 0.62 ± 0.08 0 0,000 0.79 ± 0.11 0.76 ± 0.13 0.98 0.83 ± 0.11 0 0,000 Venous Vmean 0 1.9 ± 0.09 0,000 0 0 0 0 2.37 ± 0.15 0,000 Subcutaneous Arterial Vmax 13.55 ± 2.13 4.75 ± 1.22 0.004 15.87 ± 3.67 10.99 ± 2.65 0.06 14.72 ± 2.88 3.95 ± 2.17 0.007 Vmin 0.89 ± 0.09 1.98 ± 0.57 0.05 1.77 ± 0.37 0.88 ± 0.17 0.05 0.93 ± 0.13 2.69 ± 0.43 0.05 IR 0.61 ± 0.09 0.78 ± 0.03 0.05 0.98 ± 0.13 0.76 ± 0.14 0.43 0.87 ± 0.15 0.97 ± 0.01 0.15 Venous Vmean 1.13 ± 0.45 3.78 ± 1.60 0.05 2.07 ± 0.26 1.76 ± 0.65 0.72 1.99 ± 0.33 2.98 ± 1.20 0.05 p - significance of differences in indicators before and after treatment

Claims (1)

An agent for treating local allergic exudative-inflammatory and infiltrative inflammatory processes of the skin, containing Elokom lotion with mometasone furoat as an active substance, characterized in that it additionally contains an aqueous solution of Furacilin with mass dilution of Furacilin: water as 1: 5000, in the following ratio of components about h:
Elocom lotion one aqueous solution of furatsilin 5.