RU2354379C1 - Medicinal composition (versions) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and can be used in experimental and clinical surgery, traumatology for application of film-forming compositions on wound surface. Described is medicinal composition based on medicinal preparation and BF-6 glue where as medicinal components are used xymedone, ximedone hydrochloride, dimexide, dioxydin, lidocaine hydrochloride or xymedone, brilliant green, lidocaine hydrochloride or xymedone, methylene blue, lidocaine hydrochloride or ximedone hydrochloride, potassium permanganate, lidocaine hydrochloride.

EFFECT: glue bandage prevents from external influence, contamination, stimulates formation of strong soldered layer and epithelisation.

5 cl, 1 tbl, 12 dwg , 5 ex

Description

The invention relates to medicine, namely to medicinal compositions for treating wound surfaces with polymer adhesive film-forming compositions.

Despite the centuries-old experience gained with the use of dressings by mankind for the treatment of wounds, many questions of this most important ageless medical problem remain unresolved.

The unsatisfactory local treatment of wounds with the help of various coatings, including adhesive, the most concern was the increase in the frequency of infectious wound postoperative complications. Developing purulent-inflammatory processes in the field of wounds significantly reduce the quality of treatment of patients, increase the duration of patients in the hospital [Gostishchev V.K. Purulent operative surgery. M .: Medicine, 1996; Izmailov S.G. et al. The treatment of wounds. Kazan: KSTU, 2003].

The provision of a favorable microclimate in the wound for the uncomplicated flow of the biological process, the body's implementation of a functionally complete true regeneration or repair of damaged tissue is achieved by an individual treatment program of complex therapy and is built with the necessary objective data obtained during the examination of the patient followed by the following main measures:

- elucidation and assessment of the etiology of the wound, its timing, localization and vastness, homeostasis and age of the victim, the presence of background pathological conditions and associated injuries;

- carrying out elements of classical, mechanical and physical antiseptics (excision, drainage, etc.);

- the inclusion of promising measures aimed at preventing secondary contamination;

- closure of the wound by suturing secondary sutures or plastic surgery.

In the treatment program, wound dressings with various properties are one of the important components. New advances in wound therapy have allowed the establishment of a differentiated approach, which is based on the phases of the course of the wound process. The dressing tasks include the main functions: protection from adverse external influences and the secondary entry of microorganisms, stimulation of cellular activity. The well-known popular soft dressings made of textile (gauze), non-woven (combined with a filler of cellulose or foam rubber, etc.) materials, which have a number of fundamental requirements, are required: to fine-tune a certain absorption and absorption capacity, to have sufficient gas permeability, the necessary regulation of balanced humidity and maintaining free gas exchange, which determines the desired concentration of O ₂ , CO ₂ and the pH level; be atraumatic and safe. In recent years, the flow of wound dressings has increased for dry (EU dressings, “Cetuvit”, “Cosmopor sterile”, etc.) and wet (“TenderVet” and other) wound dressings [Adamyan A.A., Dobysh S.V. , Kilimchuk L.E. and other Biologically active dressings in the complex treatment of purulent necrotic wounds. The recommendation method. Ed. V.D. Fedorova and I.M. Chizh. M., 2000, 39; Lippert H. Wound Management Guide. Publishing House: R. Hartmann, 2000].

Classic soft dressings have significant advantages in the local treatment of wounds that heal by secondary intention (per secundam intentionem), as well as old (over 6-8 hours) wounds and open tissue damage with the initial assumption of a possible genesis of primary infection. In cases where such a risk is small, which occurs with uncontaminated clean casual and surgical wounds with the hope of spontaneous epithelization, the use of various soft dressings is impractical. The latter is explained by a number of their main disadvantages:

- relative bulkiness of the structure; long duration of application (from 8 to 15 minutes);

- high mobility, especially bandage types, which narrows the indications for their use. So, it is not recommended to apply on such areas as the face, neck, joints, external genitalia of male and female organs, perineum;

- do not strengthen the contact of the edges of the wound. Their insufficient fixation does not create complete physiological rest for damaged tissues, being at the same time a limiting, restraining factor for active functional therapy;

- it is impossible to constantly monitor the condition of the wound without replacing the dressing;

- uneconomical due to the high consumption of dressings;

- there remains a high risk of developing a hospital infection due to sedimentation and cumulation of dust with the presence of pathogenic microflora;

- adsorption of microbes on the surface of the wound significantly increases the risk of anaerobic infections.

To the same extent, both bandage and bandageless (colloidal and cleol, band-aid) dressings have the same disadvantages.

Polymeric film and foaming agents used for the "open" management of clean wounds in the postoperative period and with aseptic microtraumas were also widespread. They have better prospects for healing by primary intention (per primam intentionem). With hemostasis, fibrin precipitated, although not fragile, temporarily glues the edges of the wound, and the severity of the exudative (inflammatory) phase is negligible. After the glue dries, an elastic film is formed that does not require additional dressing. The advantages of the adhesive dressing include simplicity and speed of application [Petrov S.V. General surgery. St. Petersburg: Publishing House "Doe", 1999].

One example of such a dressing is medical glue (RU) 2156140 (13) C1 7 A61L 24/00, C09J 4/04, which has low mechanical strength and low resistance to biological media - wound inflammatory exudate, weak regenerative ability and pronounced acute segmental nuclear reaction with a marked vascular component. The inflammatory response is especially high on the part of the skin and muscles, which significantly reduces the value of the practical therapeutic use of this composition in the treatment of superficial wounds.

The active influence on the course of regeneration is achieved only through adequate regulation of the favorable microclimate in the area of tissue damage in individual phases of healing, local use of pharmacological agents with various properties. Known composition based on ligfol and novocaine [RF patent No. 2272640, publ. 2006.03.27]. Its disadvantage is the need for daily application to the wound. The composition is also ineffective in case of Pseudomonas aeruginosa, is deprived of the noticeable properties of inducing tissue regeneration processes, and does not contribute to the deep penetration of drugs into damaged tissues. Ligfol, which contains humic acids, (a product of the hydrolysis of natural wood lignin) is allergenic, which narrows the indications for its use. Novocaine has weak local anesthetic qualities.

Known adhesive composition "Kagibor" [Izmailov S.G. et al. The technique of applying soft dressings. Nizhny Novgorod - Kazan, 2004, p. 71-72. RF patent No. 2188016, publ. August 27, 2002], taken by us as a prototype of the invention, containing the following ingredients in wt.%:

Ximedon 5.0-10.0 Anestezin 4.0-5.0 Hydrocortisone hemisuccinate 0.09-0.13 Boric acid 3.0-4.0 Glue BF-6 rest

Experience shows that the prototype, along with significant advantages, is endowed with a number of significant disadvantages, from which it should be highlighted:

- anestezin does not have a sufficiently high analgesic effect and often an individual hypersensitivity is encountered in its use;

- hydrocortisone hemisuccinate is a relatively expensive drug, as well as a glucocorticosteroid, it has extensive contraindications, for example, if there is an infection in the wound, it has virilizing side effects, hyperglycemia, aggravates the course of gastric and duodenal ulcers, increases blood coagulability and many other undesirable effects;

- boric acid is difficult to dissolve, often enhances the pain syndrome, which limits its use, for example, in children.

The objective of the invention is the creation of a therapeutic agent devoid of the described disadvantages and expanding the range of known medicinal compositions.

The technical result is a new drug (options).

In order to increase the arsenal of medicinal compositions and give adhesive compositions based on BF-6 glue a more pronounced regenerative ability, as well as antiseptic and anesthetic properties, several options (1-5) for a new pharmacological adhesive composition have been proposed in the following ratio of ingredients, wt.%:

1. ("Hyksidiolide")

Xymedon Hydrochloride - 8.0-10.0 Dimexide - 28.0-30.0 Dioxidine - 0.8-1.0 Lidocaine hydrochloride - 9.0-10.0 Glue BF-6 rest.

2. ("Xidioxilide")

Ximedon - 8.0-10.0 Dimexide - 18.0-20.0 Dioxidine - 0.8-1.0 Lidocaine hydrochloride - 9.0-10.0 Glue BF-6 rest.

3. ("Xybrilide")

Ximedon - 6.0-6.5 Brilliant green - 1.8-2.0 Lidocaine hydrochloride - 9.0-10.0 Glue BF-6 rest

4. (Xymethylide)

Ximedon - 6.0-6.5 Methylene blue - 1.8-2.0 Lidocaine hydrochloride - 9.0-10.0 Glue BF-6 rest

5. ("Hyksalid")

Xymedon Hydrochloride - 8.0-10.0 Potassium permanganate - 0.2-0.4 Lidocaine hydrochloride - 9.0-10.0 Glue BF-6 rest

The presented ratio of components is based on the data of many years of our own clinical and experimental studies, taking into account the available literature information [S. Kurbangaleev Purulent infection in surgery. M .: Medicine, 1985; Konychev A.V. Purulent-inflammatory diseases of the upper constant. St. Petersburg: Nevsky Dialect 2002; Podushkina I.V. Topical use of Xymedon and photomagnetotherapy for the treatment of long-term non-healing wounds and trophic ulcers in the outpatient surgical practice of a military doctor: Abstract. diss. Cand. honey. sciences. N. Novgorod, 2000; Mashkovsky M.D. Pharmacological agents. M .: Medicine, 2004].

Xymedon (Ximedonum) and Xymedon hydrochloride (Hydrochloridum Ximedoni) have a polyvalent effect, from which the stimulation of repair processes in damaged tissues should be emphasized. In the conditions of the surgical clinic and in animals, reparative abilities, antiseptic, desensitizing properties and the harmlessness of their local application have been studied. The effectiveness of the drugs was established both in monotherapy and in combination with other drugs (dioxidine, lidocaine, etc.) with some difference in the degree of exposure in the phase of inflammation. Xymedon hydrochloride has a pronounced dehydrating effect, which makes it advisable to use it in cases with prevailing tissue swelling [Patent RU 2261699, publ. 10/10/2005].

Dimexide - Dimexidum (dimethyl sulfoxide - DMSO) is a chemical antiseptic and oxidizing agent, it is endowed with anti-inflammatory, analgesic and desensitizing properties, and it also has a very important ability to transport other drugs, for example, xymedon and xymedon hydrochloride. In this connection, potentiation of their action occurs, due to the penetration of pharmacopyrimidine derivatives into tissues through cell membranes, which is confirmed by our observations.

Dioxidin (Dioxydinum) is known as a broad-spectrum drug used in various purulent-inflammatory processes in the form of solutions and ointments, but with monotherapy, side effects (dyspeptic reactions, fever, headache) are possible. Undesirable listed responses are not observed when using the drug in our proposed medicinal composition, without reducing its main antimicrobial effect.

Lidocaine (Xylocaine, Xicaine) hydrochloride (Lidocaini hydrochloridum) as a local anesthetic in the form of a solution is used for infiltration and terminal anesthesia. Isolated use of the drug often leads to dermatological reactions (urticaria, skin rash, etc.), which is not observed when it is included in our composition. You should take into account the antiarrhythmic property of the drug [Mashkovsky M.D. Pharmacological agents. M .: Medicine, 2004].

The inclusion of dyes - methylene blue (Methylenum coeruleum) and brilliant green (Viride nitens) and a strong oxidizing agent - potassium permanganate (Kalii permanganas) was made to enhance the adhesive composition of antiseptic properties. Giving the composition a color makes it possible to use it with greater rationality for small superficial injuries, when strict localization of the application of the drug is required in the absence of the need for long-term permanent monitoring of the patient, for example, on an outpatient basis.

The claimed invention proposed a number of medicinal adhesive compositions for the possible implementation of a new individualized approach to the treatment of wounds, based on modern criteria for dressings, depending on the etiology, extent of damage, degree of infection and exudation.

The stages of the wound process were mainly used: exudation, granulation, epithelization. This approach makes it possible to use the proposed interactive dressings in the doctor’s daily practice with maximum efficiency, getting good results.

EXAMPLE 1 (components in wt.%)

Xymedon Hydrochloride - 9.0 Dimexide - 29.0 Dioxidine - 0.9 Lidocaine hydrochloride - 9.5 Glue BF-6 - the rest

Patient Sh., 47 years old, was admitted to a purulent-septic compartment with an extensive mechanical random wound of the left buttock. Body temperature 40 ° C. Against the background of generally accepted complex therapy, dressings with an adhesive composition were applied locally (option 1). The wound on the 8th day cleared of purulent-fibrinous deposits. Complete healing occurred on the 10th day after the application of secondary early sutures.

EXAMPLE 2 (components in wt.%)

Ximedon - 9.0 Dimexide - 19.0 Dioxidine - 0.95 Lidocaine hydrochloride - 9.0 Glue BF-6 - the rest

Patient V., 40 years old, was admitted to the surgical department 2 hours after the attack of the disease. On examination, signs of acute adhesive obstruction were noted. A year ago, he was operated on for a closed abdominal injury. An emergency laparotomy was made with dissection of the interlobular adhesions, a postoperative median wound of the bruise with the application of an adhesive composition (option 2) according to our technology. Healing by first intention.

EXAMPLE 3 (components in wt.%)

Ximedon - 6.2 Brilliant green - 1.9 Lidocaine hydrochloride - 10.0 Glue BF-6 - the rest

Patient S., 26 years old, was treated on an outpatient basis with a superficial wound in the chin area without signs of suppuration. A skin defect of 3 × 1.5 cm was closed by the adhesive composition of option 3. Uncomplicated healing on day 8.

Example 4 (components in wt.%)

Ximedon - 6.0 Methylene blue - 1.9 Lidocaine hydrochloride - 9.0 Glue BF-6 - the rest

Patient J., 21 years old, was admitted to outpatient treatment with a diagnosis of a cut wound in her right forearm. The wound with smooth edges is sutured by nylon, which is caused by its localization and optionally applied composition option 4. Sutures were removed on the 6th day, healing by primary intention.

EXAMPLE 5 (components in wt.%)

Xymedon Hydrochloride - 10.0 Potassium permanganate - 0.3 Lidocaine hydrochloride - 9.8 Glue BF-6 - the rest.

A 76-year-old patient was admitted to the surgical department with a purulent necrotic wound in the right thigh. Suffers from diabetes. The wound does not heal for 2 months, although various ointment dressings have been used. Assigned to complex therapy with the correction of carbohydrate metabolism. Topically applied dressings with a variation of composition 5. Slow healing by secondary intention.

Clinical use of the claimed compositions showed that there was an increase in painkiller and adhesive, desensitizing and regenerative abilities. It was not the additive activity of the proposed combination that was ascertained, but the synergistic effect - the effect exceeds the sum of the action of the individual components, which is most likely due to the potentiating effect of the ingredients on various aspects of microbial metabolism, cell proliferation, angiogenesis and other growth factors - cell processes involved in wound healing. Compositions by their pharmacological properties provide optimal conditions for uncomplicated restoration of damaged tissues in all its phases, which is confirmed by the results shown in table 1.

Table 1 shows the results of using the claimed medicinal composition (options 1-5) in the treatment of wounds depending on the clinical syndrome in comparison with the prototype composition Kagibor.

The process of preparing the proposed composition is carried out in accordance with accepted comprehensive methods of the State Pharmacopoeia by simple mixing of the components [Pharmacist Handbook. / Ed. A.I. Tenzova. - M.: Medicine, 1973. 584 p.].

Kagibor (composition according to the prototype) is applied to the wound by lubricating it, for example, with a brush or swab, which leads to excessive additional injury to the tissues. In addition, this technology does not guarantee the achievement of totality of the treatment of the wound surface and the paravular region. There is also a high risk of implantation infection due to tearing of the villi of the hand with their skidding into the wound. Thus, it is provided to reasonably seek a more advanced technology for applying an adhesive composition to a wound.

A device for applying drugs is known, which contains a housing with a hole, while the internal cavity of the housing is filled with porous capillary material impregnated with a liquid drug, and the hole is mounted with the possibility of linear movement and fixation due to friction-adhesion forces with the housing capillary rod, one the end contacting with the porous material inside the housing, and the other protruding outward of the housing [RU 2042362 C1, 1995.08.27].

A device for applying pastes and gels to hard-to-reach areas of the body, containing a container with a flexible shell installed in it, forming a cylindrical cavity, a nozzle, a cylinder with compressed gas and a locking device with a channel connecting the pneumatic cavity and the atmosphere in which the flexible shell is fixed at one edge to the lower base of the tank around the circumference, and the other to the outer surface of the compressed gas cylinder. In this case, the nozzle is installed between the pneumatic cavity and the cavity formed by the flexible shell and the cylinder with compressed gas [RU 2185200 C1, 2002.07.20].

A device for coating a surface of a skin or wound is known, including a housing in which a means for supplying a jet of hardening liquid is placed, and which contains an optical system that provides the required degree of solidification of the liquid [RU 2002122705 A, 2004.03.10].

A device is known for coating a surface of a skin or wound formed from a jet of hardening liquid, including a device for forming a jet equipped with a capillary, a source of high electric voltage and a device for creating a focusing electrostatic field around the jet, made in the form of an electrode placed around the axis of the capillary in immediate proximity to its outlet, while the capillary and electrode are connected to a source of high electrical voltage, one of the pole which it is intended for electrical connection with the body [RU 2002122705 A, 2004.03.10].

However, these devices are complex and inconvenient to operate. The same disadvantages are devices [RU 2006111484 A, 2004.08.10, RU 2002107499 A 2003.11.27].

Known application for applying to the wound of adhesive compositions of special devices in the form of a spray can (Akutin, Nobekutan, Aeroplast, Akutol, etc.), where the adhesive is under pressure from 1.5 to 5 atm. The device consists of a body in the form of a can with a mixture of a drug with liquefied gas and a spray head. By pressing the latter, the gaseous phase of the filler develops and the dispersed adhesive is ejected outward by a jet.

A known applicator, including a canister for storing liquid, an absorbent tampon, means for fixing an absorbent tampon against a hole for liquid to exit the canister, the fixation means for a tampon are integral with the canister and are made in the form of an arch carrying a tampon. The arch has side legs connected at its ends to the spray can and is deformed in a helical fashion to enable rotation of the arch [RU 2248816 C2, 2005.03.27].

Usually, the wound surface is treated from a distance of 30 cm from it. However, the use of aerosol cans is not without negative aspects:

- irrationality of use due to excessive loss of substance;

- application under pressure of finely divided particles of medicinal substances - aerosols in a dissolved state leads to its inevitable entry into the respiratory tract, eyes, skin and mucous membranes of medical personnel, which is fraught with the danger of allergic reactions;

- the inability to treat the scalp, face;

- frequent failure of the device (pressure drop, seizing of the head, etc.);

In order to eliminate the described disadvantages of the prototype of the invention, a more economical consumption of the adhesive composition, to expand its use in various areas of the body, a new device for applying pharmacological agents is proposed. The device contains a set of soft-elastic rollers of various shapes and sizes, with their possible movable mounting on the handle.

Figure 1 schematic diagram (1st option): shows a General view of the device Assembly; figure 2 - the working part with a latch; figure 3 is a cylindrical roller with a missing axis; figure 4 - spherical roller; figure 5 is a section aa in figure 4; Fig.6 is a section bB in Fig.3; Fig.7 - axis options; on Fig - section bb in Fig.7 (b); Fig.9 (2 option) - grip clamp of the roller; figure 10 - roller with two protruding ends of the axis; figure 11 is a diagram of a grip spring-like gripper - roller lock; on Fig - tightly closed jar with submerged rollers.

The applicator device (option 1) contains a handle 1, at the end of the refined working part, the rod 2 is movably fixed on the axis 3, a soft-elastic roller-roller 4 located perpendicular to the rod 2. Directly at the end part of the rod 2 there is a fixed protrusion the retainer 5, on which the roller 4 is mounted, the rotation of which is possible due to the presence of a rigid axis 3, passed exactly in the center longitudinally through the entire thickness of the roller 4. The rollers 4 are made of various shapes: cylindrical (figure 3), spherical (figure 4 and 5), sizes and sizes shaped relief of the outer surface (Fig.6) - smooth "a", ribbed "b". Axis 3 (Fig. 7) can be made (variants) of integral (a), hollow (cylindrical) tubular (b) with lateral through holes (6) (serve for the introduction of adhesive compositions - solutions), as well as integral (Fig.7c) ) with a simplifying conical shoulder 7, preventing a retrograde exit from the thickness of the roller 4. Axis 3 can serve as injection needles manufactured by the domestic industry. One of the ends of the axis 3 is made in the form of a conical hollow socket 8 (Fig. 7), which is used for fastening on the protrusion 5 of the rod 2. It is possible to produce cylindrical rollers 4 integral with the axis 3 with a porous soft elastic sleeve (not shown).

The second variant of the applicator device is a fork-shaped spring-loaded, plate-shaped retainer (Fig. 9) - a grip coming from the end part of the working part of the rod 2. In this case, the roller 4, having freely protruding ends 10 of the axis 3, is attached to the springs of the ends of the grip 9.

Pre-assembled rollers with missing axes are immersed in a glass vessel - Bix 12 (sterilized). Sterilization is carried out in an autoclave, in Bix 45 minutes. Compositions are sterilized separately under the same conditions.

Before use, the Bix 12 is opened, the roller 4 is pulled out with a tool (Fig. 1), grabbing it by the protruding socket 8 of the extended hollow end of the axis 3, and the handle 2 is mounted on the protrusion-latch 5 (previously sterilized in one of the traditional ways) by means of rolling (applications) and not traction!) of the roller 4 along the wound surface with moderate pressure, uniformly apply the adhesive composition. After 7-8 seconds of exposure, the 2nd, 3rd and 4th layers are applied. Additionally, the bandage is not used. The patient is allowed to move after the operation. With an uncomplicated course of the wound process, the sutures are removed at the usual time with the simultaneous removal of easily peeling adhesive film.

Experimental (30) and clinical (70) observations have shown that the medicinal adhesive compositions and device applicators presented by us for their application to tissues have significant advantages. When using them are provided:

- the technical simplicity and short duration of the procedure, which is of particular importance in the outpatient environment of the surgeon;

- the reliability of the formed thin, light film having high adhesive ability;

- unimpeded possibility of practical application in all areas of the patient's body;

- the creation of a durable contact of the edges of the wound, its physiological rest are necessary basic conditions for functional treatment;

- lightweight visual monitoring of the healing process;

- significant economy due to the exclusion of expensive tissue dressings;

- regenerative activity of the composition, which is proved by studies.

Table 1
The results of the use of the medicinal composition in the treatment of wounds depending on the clinical syndrome Clinical syndrome Medicinal composition (variants of the claimed compounds) The adequacy of healing,% The control Options one 2 3 four 5 Conditionally clean wounds 3 87 90 89 Exudation: Necrosis 5 79 90 Infection one 81 89 Fibrin 5 75 92 Granulation 2 74 95 Epithelization 3 80 89

Healing was considered adequate if no complications were noted on the 8th day of treatment, the wound was epithelized, or a clear tendency was observed for a favorable course of the wound process.

Control is carried out using a prototype.

Claims (5)

1. A medicinal composition based on a medicinal product and glue BF-6, characterized in that in its composition as active active ingredients it contains ingredients in the following ratio, wt.%:
xymedon hydrochloride 8.0-10.0 dimexide 28.0-30.0 dioxidine 0.8-1.0 lidocaine hydrochloride 9.0-10.0 glue BF-6 rest 2. A medicinal composition based on a medicinal product and glue BF-6, characterized in that in its composition as active active ingredients it contains ingredients in the following ratio, wt.%:
xymedon 8.0-10.0 dimexide 18.0-20.0 dioxidine 0.8-1.0 lidocaine hydrochloride 9.0-10.0 glue BF-6 rest 3. A medicinal composition based on a medicinal product and glue BF-6, characterized in that in its composition as active active ingredients it contains ingredients in the following ratio, wt.%:
xymedon 6.0-6.5 diamond green 1.8-2.0 lidocaine hydrochloride 9.0-10.0 glue BF-6 rest 4. A medicinal composition based on a medicinal product and glue BF-6, characterized in that in its composition as active active ingredients it contains ingredients in the following ratio, wt.%:
xymedon 6.0-6.5 methylene blue 1.8-2.0 lidocaine hydrochloride 9.0-10.0 glue BF-6 rest 5. A pharmaceutical composition based on a medicinal product and BF-6 glue, characterized in that in its composition as active active ingredients it contains ingredients in the following ratio, wt.%:
xymedon hydrochloride 8.0-10.0 potassium permanganate 0.2-0.4 lidocaine hydrochloride 9.0-10.0 glue BF-6 rest

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