RU2405536C2 - Ointment for thermal injury treatment and method of treatment with it - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention belongs to medicine, it is ointment for thermal injury treatment and is based on lard; it includes biologically active component and features with visceral fat and dihydroquercetin as biologically active component; ointment's components are in special mass percent ratio; also thermal injury method by application of ointment of abovementioned composition.

EFFECT: invention provides prevention of coarse eschars and cicatrices development due to acceleration of upper epithelial layers development and simultaneous retardation of younger granulation tissue proliferation.

4 cl, 3 ex

Description

The invention relates to medicine, in particular to ointments for the treatment of thermal burns, a method of treating these injuries using the specified ointment.

The patent RU N 2160092 describes an antimicrobial preparation for treating infected wounds, burns, trophic ulcers and pustular skin diseases. The composition of the antimicrobial preparation, wt.%: Dioxidine - 4.0-5.0; novocaine - 0.3-0.5; fatty oil (stone fruit) - 10.0-20.0; aubazidan - 0.6-0.8; distilled monoglycerides - 2.0-3.0; glycerin - 4.0-5.0; Aerosil - 2.0-3.0; nipagin - 0.10-0.11; nipazole - 0.10-0.11; distilled water - up to 100.0.

Common signs of a known and claimed ointment is the use of a fat base.

The disadvantages of the known funds is the use of chemicals obtained using complex and expensive technologies, the multicomponent ointment.

In patent RU N 2287324 an ointment for treating burn wounds is described, containing the following components, wt.%: Wax 13-15; rivanol solution 1.2-1.3; tannin 3-5; glycerin 15-20; vegetable oil - the rest.

Common signs of a known and patented ointment is the use of a fat base and biologically active components.

The disadvantages of the known ointment are the inaccessibility of beeswax, its high cost, the use of non-natural products, the complex production technology, costly material and energy resources. The preparation of the ointment is technically difficult and requires special equipment.

A method for treating burns by applying an ointment to a damaged surface is also described there.

Common signs of the known and proposed method of treatment is the application of an ointment to a wound, as well as the use of a fat base and biologically active components in the composition of the ointment.

From patent RU N 2256441 an ointment is known for the treatment of burns, purulent and infected wounds of various etiologies. The ointment contains, wt.%: 20-30 wax, 30-40 butter, 15-20 vegetable oil, 15-25 rosin.

The method of preparing the ointment involves grinding the components, which are then placed in an enameled container, then melted and brought to a boil with continuous stirring. The resulting product is filtered, then hot poured into molds.

Common signs of a known and patented ointment is the use of animal fat and biologically active components.

The disadvantages are the need for grinding the ingredients, their inaccessibility, high cost and deficiency.

A method for treating burns, purulent and infected wounds, which is carried out by applying a thin layer of ointment to a dense cotton tissue and applying it to the affected area, is also described there.

Common signs of the known and proposed methods of treatment is the application of the ointment and its retention on the wound, as well as the use of fats and biologically active components in the composition of ointments.

The disadvantage is the formation of scars that appear on the site of a healed wound when stimulating the development of young granulation tissue; the need to use a dressing that impedes the access of light, which is necessary for the involvement of restoration mechanisms in wound healing (Peau et environnement / Dubertret Louis // Cr Ser. 2 - 200. - Vol.323.- No. 7.- P.629-632) .

A burn (according to example 4 of patent 2256441), associated with blackening of the skin, necrosis of the skin and internal organs, refers to severe burns of III B - IV - degree. Such burns cannot be healed within 14 days without surgery. Even burns of III A - degrees need longer conservative therapy. The healing process is 3-6 weeks (Loginov L.P. Modern principles of local treatment of thermal burns / L.P. Loginov // Russian Medical Journal. - 2001. - T. 9. - No. 34. - P.123-125 )

From patent RU N 2168999, an ointment is known for the treatment of deep, extensive burn and infected wounds and ulcers, including polyfler flower honey, pine resin, ghee (cow) oil with a certain ratio of components.

Common signs of a known and patented ointment is the use of animal fat and biologically active components.

The disadvantages of the known ointment is the inaccessibility and high cost of the components of the ointment.

The patent RU N 2165754 describes the ointment closest (prototype) in technical essence for the treatment of purulent-inflammatory diseases, burns, inflammatory joint diseases, trophic ulcers and long-term healing wounds. The ointment contains, parts by weight: beeswax (10-300), pine resin (10-300), olive oil (300-600), pork fat (100-300), which is used as fat obtained by melting pork lard .

According to this patent, olive oil is 450 parts by weight. heated to the melting point of fat and boiled for 3-4 minutes. Then, pork fat is introduced, 150 parts by weight, the mixture is heated to boiling, beeswax 200 parts by weight is added to the boiling oil and fat mixture, then pine resin is 60 parts by weight, boiled until the resin is completely dissolved 1.5-2.5 minutes and cooled to room temperature. The cooled ointment is filtered through a fabric filter, and after filtering it is poured into glass containers.

The disadvantages of the ointment for the prototype are the inaccessibility and high cost of beeswax, pine resin, olive oil, repeated heat treatment of animal fat (melting pork fat) and repeated heating of the mixture of ingredients in the manufacture of ointment, associated with the destruction of biologically active components and the deterioration of their active principle.

The specified ointment contains pine resin, the use of which requires preliminary cleaning, which complicates the preparation of the ointment itself. In the process of pre-cleaning the resin, it is possible to change its composition, which does not allow to obtain the effect that the authors of this invention provided.

From the patent RU N 2165754, the closest (prototype) method for treating burns is known, which is carried out by soaking in the affected area (for 8-24 hours) an ointment, applied in a thin layer on a dense cotton fabric. After the specified time, the ointment dressing is removed and a new dressing with a new portion of the ointment is applied to the burn.

The disadvantages of the method are the need to use a bandage that prevents the access of light, which is necessary to involve restoration mechanisms during wound healing, in the repeated heat treatment of lard and a mixture of ingredients that reduces the biological activity of the components. Therefore, the ointment is used to treat burns only of the 1st and 2nd degree of a small area of damage. It does not seem possible to use it to treat more severe burns with a large area of damage. Full recovery when using the ointment according to the prototype was observed after 3 days, which contradicts the practice of treating burns (Loginov L.P. Modern principles of local treatment of thermal burns / L.P. Loginov // Russian Medical Journal.-2001. - T.9 . - No. 34. - S.123-125).

The objectives of the group of inventions are:

- expanding the range of inexpensive and affordable components of the ointment for the treatment of thermal burns of the III A-degree with a large area of damage;

- expanding the arsenal of ointments of simple composition with good physicochemical and consumer properties for the treatment of thermal burns of the IIIA degree with a large area of damage;

- the development of a simpler, inexpensive and not requiring complex equipment technology for the preparation of ointments;

- the development of a simpler and at the same time effective way of its application.

The technical result of the group of inventions is:

- the possibility of treating thermal burns IIIA-degree with a large area of damage without the use of dressings;

- preventing the formation of a hard scab and scars by increasing the rate of formation of the upper epithelial layers while inhibiting the maturation of young granulation tissue (unexpected effect);

- the absence of a pronounced annoying side effect;

- simplifying the composition of the ointment and the technology for its preparation;

- reduction of material and energy costs.

The elimination of these drawbacks and the achievement of the claimed technical result from the implementation of an ointment for the treatment of thermal burns based on pork fat, including a biologically active component, is achieved by the fact that, as pork fat, the ointment contains internal pork fat, includes dihydroquercetin as a biologically active component in the following ratio of components , wt.%:

Interior Pork Fat - 97

Dihydroquercetin - 3.

In this case, the interior pig fat is preliminarily melted in a water bath before use.

A comparative analysis of the prototype and the claimed ointment shows that the use of pork fat and biologically active components is common in their composition.

A distinctive feature of the claimed ointment is that, as pork fat, the ointment contains interior pork fat, includes a dihydroquercetin as a biologically active component in the following ratio, wt.%:

Interior Pork Fat - 97

Dihydroquercetin - 3.

In this case, the interior pig fat is preliminarily melted in a water bath before use.

The ointment is obtained by adding dihydroquercetin to a melted in a water bath and filtered through a filter consisting of four layers of medical gauze, interior pork fat. The components are mixed with constant stirring. After cooling, the ointment is poured into glass containers. Ointment at room temperature is a homogeneous mass of dense and dense texture of a pale yellow color. When in contact with the body, the ointment softens and becomes plastic. It does not dissolve in water. Non toxic

A method for the treatment of thermal burns by applying an ointment to the affected area and maintaining it, which contains interior pig fat and dihydroquercetin in the following ratio, wt.%:

Interior Pork Fat - 97

Dihydroquercetin - 3.

In this case, the ointment is applied to the burned surface once a day with a layer of 0.5 mm and kept on the affected area without a bandage.

A comparative analysis of the prototype and the proposed method shows that the common signs are the application of ointment to the affected area and its exposure to it.

A distinctive feature of the proposed method of treatment is that the ointment includes interior pork fat and dihydroquercetin in the following ratio of components, wt.%:

Interior Pork Fat - 97

Dihydroquercetin - 3.

In this case, the ointment is applied to the burned surface once a day with a layer of 0.5 mm and kept on the affected area without a bandage.

According to the invention, a method of treating thermal burns consists in applying the ointment with a layer of 0.5 mm gauze swab to the affected area once a day, after which the residues are removed and a new portion of the ointment is applied to the wound until the epithelium is completely regenerated. With this treatment of thermal burns, the claimed ointment heals within 40 days, which is consistent with the practice of conservative treatment of such burns.

As follows from the above review of patent and scientific and technical literature, the claimed ointment containing the combination of the above ingredients in the proposed quantitative ratio, and the treatment method using it are new, which allows us to conclude that the claimed technical solution is new.

The invention is illustrated by the following examples.

Example 1. Preparation of ointment.

To prepare 100 g of ointment, take 97 g of melted in a water bath and filtered through a filter consisting of four layers of medical gauze, interior pork fat, to which 3 g of dihydroquercetin is added (the chemical name is 2,3-dihydro-3,5,7- trihydroxy-2- (3,4-dihydroxyphenyl) 4H-1-benzopyran-4-one)). The components are mixed with constant stirring. The resulting product has the following ratio of components, wt.%:

Interior Pork Fat - 97

Dihydroquercetin - 3.

Then the ointment is cooled and poured into glass containers. The product at room temperature is a homogeneous mass of dense and dense texture of a pale yellow color. When in contact with the body, the ointment softens and becomes plastic. It does not dissolve in water. Non toxic

Example 2. The treatment of thermal burns.

The essence of the treatment is illustrated by the results of observations of the healing process of the claimed composition of the ointment in the burn disease model. Studies were carried out on outbred rabbits in the amount of 6 pieces. The animals were injured with a special device (Disease Modeling / edited by Prof. S.V. Andreev. - M: Medicine. - 1973. - 336 p.), Resulting in a IIIA degree burn with an area of 20.5 cm ² ( 16%). It is known (Mikhalchik E.V. Prophylactic and therapeutic effect of a complex antioxidant drug in case of burn injury in rats / E.V. Mikhalchik and others // Bulletin of experimental biology and medicine. - 2004. - T.138.-No. 3. - C .299-301) that thermal injury causes the release of cytotoxins and prostoglandins, resulting in increased interaction between leukocytes, platelets and endothelial cells. The activation of leukocytes and platelets leads to an increase in the formation of reactive oxygen and nitrogen forms, which, combined with increased adhesion of polymorphonuclear leukocytes to the endothelium, creates a threat of oxidative damage to their own organs and tissues.

The burn treatment was performed by applying the ointment to the wound with a gauze swab once for 24 hours. The dynamics of wound healing was monitored on days 1, 3, 7, 14, 21, 30, 40. Throughout the experiment, physiological indicators were taken: the area of the wound, body temperature and wounds, the module of the complex resistance of the skin. The dynamics of wound healing was confirmed morphologically.

After applying a burn to experimental animals and treating the wound with the claimed ointment, a significant decrease in body temperature is noted by the first day, compared with the six-hour mark when it increased. The temperature in the wound also decreases, which is associated with the components of the test ointment, which play the role of an antioxidant in the wound, and, as a result, lowers its and body temperature. By the first day, there is an increase in white blood cells and a decrease in red blood cells. The erythrocyte sedimentation rate (ESR) by the first day is reduced. The number of lymphocytes varies throughout the experiment, while remaining normal. No sharp changes in the content of total plasma protein were noted.

On the third day of treatment, the complex resistance module and the thickness of the skin fold show the formation of a scab. A blood test shows the absence of an inflammatory process and oxygen deficiency in the tissues. The weight of animals by the third day, compared with the first, falls. This is explained by the appearance of toxic compounds in the wound, an oppressed state appears in experimental rabbits, fluid loss through the wound surface, and a general lack of appetite, as evidenced by hematological parameters. Further, after the formation of a dense scab and daily treatment, the weight of the experimental animals begins to increase until complete healing. In this case, the body temperature returns to the original. The temperature in the wound area is reduced.

By the seventh day of treatment, demarcation of dead skin from viable tissues is observed, and epidermal proliferation under the scab.

By the fourteenth day, the healing stage begins, the scab decreases in size and begins to separate from the wound surface and is easily removed. A decrease in body temperature is observed. The temperature of the wound decreases, and the complex resistance modulus rises slightly. Swelling in the tissues increases, which is confirmed by the onset of scab rejection and the deep penetration of the drug throughout the depth of the damaged tissues of the wound surface.

The modular resistance of the skin decreases and levels as the damaged skin surfaces of the experimental rabbits heal. The content of white blood cells and red blood cells is returning to normal. Hematological indices at 14, 21, 30 days are normal.

The wound surface is reduced due to the epithelization of its edge parts. Morphological examination shows the formation of papillae, hair follicles and sebaceous glands.

By the twenty-first day a thin layer of granulation tissue appears. By this time, the connective tissue is cleansed of the dead components of the dermis and skin appendages, which is confirmed by changes in biochemical and hematological parameters.

By the thirtieth day there is a sharp decrease in the area of the wound surface. The scab, which is still soft, continues to be rejected, which simplifies the medical care of this group.

The scab that has moved away from the wound surface is easily removed using surgical instruments. The behavior of the animal is evaluated as positive, nothing interferes with movement.

The area of the wound according to the index L.N. Popova in the treatment with patentable ointment decreases from 21 days to 30 days by 8.6%, which indicates the pronounced effectiveness of local wound treatment.

By the fortieth day, when the wounds were practically healed, the content of hemoglobin, reticulocytes, the number of lymphocytes, total protein and albumin returned to normal. Morphological studies have shown that the regenerate has acquired a multilayer structure over most of its length.

By the forty-seventh day, the wounds had completely healed and healing occurred without scarring. There is an intense overgrowing of healthy skin with hair.

During treatment, it was shown that the ointment does not spread on the surface, does not have a pronounced irritating side effect, its use does not require the use of a dressing, as a result of which light is accessible to the burn surface. The latter contributes to the involvement of restorative mechanisms in wound healing.

Ointment has an effect in three directions.

1. In the presence of a burn wound, the action of the ointment is aimed at cleansing and healing the wound, limiting the focus of damage when removing inflammatory manifestations.

2. The ointment acts on the scab, softening it, thereby preventing infection and the formation of new wounds due to damage to the freshly formed skin during combing and tension during the formation of the scab.

3. Under the action of the claimed ointment, the healing of a burn wound proceeds gently, evenly over the entire surface, without leaving scars.

The therapeutic effect of the ointment is based on the total manifestation of the following properties of its components:

- the component of the ointment - interior pig fat is a solvent and a filler for the active principle - dihydroquercetin;

- dihydroquercetin acts as a binder, stabilizer, preservative and active ingredient in the healing process of a burn wound.

It has been shown that the use of interior pig fat as part of the ointment provides good ointment permeability through the scab and interaction with the damaged surface, and its long-term preservation on the wound. The softening of the scab leads to painless rejection of necrotic tissue with simultaneous, complete inhibition of the maturation of young granulation tissue both from the edges of the wound and from the bottom of the wound. The latter is inherent in flavonoid preparations and indicates the biostimulating effect of the ointment.

The combined effect of dihydroquercetin and interior pig fat is directed to the binding of free radicals and cytotoxins in the wound surface, their elimination from the body and the prevention of oxidative damage to their own organs and tissues. Studies have shown that the drug has a therapeutic effect on the affected skin by limiting the focus of inflammation.

The possibility of using a patented ointment for the effective treatment of thermal burn wounds of the IIIA degree with a large area of damage has been experimentally established.

Example 3. The study of the toxicity of dihydroquercetin.

The toxicity of dihydroquercetin has been studied in white sexually mature outbred mice and rats (males). Dihydroquercetin belongs to substances of the 4th hazard class and according to our data its LD ₅₀ = 6000 mg / kg (Shchukina O.G. et al. On the assessment of acute toxicity of dihydroquercetin from Siberian larch. // Bulletin of the Samara Scientific Center of the Russian Academy of Sciences, 2007, spec. release "Security. Technologies. Management", t.1, p.152-156).

The tests carried out on a model of burn disease confirmed the confident achievement of the tasks. Created from affordable, inexpensive, natural (natural) products without chemical additives, the ointment and the method of its application allowed to increase the effectiveness of treatment (treat more severe burns of the IIIA degree with a large area of damage). An unexpected effect was obtained, which consists in preventing the formation of a hard scab and scars by increasing the rate of formation of the upper epithelial layers while inhibiting the maturation of young granulation tissue.

The implementation of the group of inventions allows you to expand the range of simple on the way to obtain drugs for the treatment of thermal burns. The above detailed description of the composition of the ointment for the treatment of thermal burns, the method of its preparation and use does not raise any doubts about its feasibility - the components of the proposed ointment are available and all stages of the manufacturing technology are not difficult, which reduces material and energy costs.

The patented group of inventions meets the criterion of the invention “inventive step”, since technical solutions have not been identified from the prior art, the essential features of which would ensure the fulfillment of the same technical task and achievement of the technical result, which this group of inventions is aimed at.

Implementation of the claimed group of inventions eliminates the disadvantages of analogues and prototype and obtain the claimed technical result, which is achieved not by the additive contribution of each component, but due to the total synergistic effect.

Claims (4)

1. An ointment for the treatment of thermal burns based on pork fat, including a biologically active component, characterized in that the pigment ointment contains interior pig fat, and as a biologically active component includes dihydroquercetin in the following ratio, wt.%:
Interior Pork Fat 97
Dihydroquercetin 3 2. Ointment for the treatment of thermal burns according to claim 1, characterized in that the interior pig fat before use is pre-melted in a water bath. 3. A method of treating thermal burns by applying an ointment to the affected area and maintaining it, characterized in that the ointment contains interior pork fat and dihydroquercetin in the following ratio, wt.%:
Interior Pork Fat 97
Dihydroquercet 3 4. A method of treating thermal burns according to claim 3, characterized in that the ointment is applied to the burned surface once a day with a layer of 0.5 mm and kept on the affected area without dressing.