RU2790489C2 - Wound-healing and anti-inflammatory spray - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and can be used for the treatment of linear and planar wounds. A spray for the treatment of linear and planar wounds is proposed, containing as active components: 2-ethyl-6-methyl-hydroxypyridinium N-acetyl-6-aminohexanoate, silver N-acetyl-6-aminohexanoate and ionol in the amount of 5.0, 0, 1 and 1.0 wt.%, respectively. The invention also relates to a method for the treatment of linear and planar wounds, including applying the specified spray on the wound surface 3 times a day.

EFFECT: acceleration of wound healing with the formation of a cosmetically less rough scar at the site of injury without the formation of a local inflammatory reaction is provided.

2 cl, 7 tbl, 6 ex

Description

The invention relates to medicine, specifically to a spray suitable for the treatment of linear and planar wounds, containing derivatives of N-acetyl-6-aminohexanoic (acexamic) acid.

The level of technology.

Known complex salts of acexamic acid, stimulating the regeneration of bone tissue, accelerating the processes of reparative osteogenesis, stimulating the mineralization of bone tissue in osteoporosis.

2-Ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate compound 1

N-Acetyl-6-aminohexanoate silver compound 2

(Patent RF 2668966)

In modern medicine, drugs are produced in various forms that are convenient for delivering the active substance to the diseased organ.

One such form for external use today is a spray. The application of the medicinal composition in the form of a spray on the skin, mucous membrane of the throat or other affected area allows you to evenly apply the medicine without disturbing the patient by touching and without the risk of introducing an infection. Sprays in recent years is a new popular form of medicines. The spray proved to be an extremely effective and convenient dosage form for external, local intranasal action, which has certain advantages.

- Sprayed on a sore or affected area, the spray has an extremely fast therapeutic effect. The speed of exposure and the effectiveness of the drug in some cases is comparable to intravenous injection.

- The dispersed form increases the biopharmaceutical and pharmacological activity of the drug, which makes it possible to manage with lower doses of the active substance. This, in turn, reduces unwanted side effects and the effectiveness of treatment.

- Due to the microscopic size of the drug particles, it is much easier to absorb the surface of the skin and mucous membranes.

- The spray can be used in cases where the oral method of taking drugs does not give the desired effect, since the active substance is destroyed by gastric juice.

- Before spraying, the medicine is in a sterile, clean state in a hermetically sealed vial. The drug retains its quality, being in the form that pharmacists considered optimal for influencing the patient's body.

- With the help of a dosing valve, the medicine is sprayed in precisely measured portions, excluding overdose.

- A convenient and fast method of application is available to almost every patient, regardless of his physical condition.

http://yandex.kg/clck/jsredir?bu=

Currently, in medical practice, a significant number of sprays are used to treat burns, containing various synthetic and herbal medicinal substances.

Olazol

Olasol, ALTAIVITAMINS CJSC (Russia).

Aerosol for external use 1 bottle:

benzocaine 1.62 g

boric acid 270 mg

sea buckthorn oil 5.4 g

chloramphenicol 1.62 g

Healing agent. It has an anesthetic and antibacterial effect, reduces exudation, promotes tissue regeneration and accelerates the process of wound epithelialization.

Panthenol

Panthenol, MICROPHARM LLC (Ukraine)

Presentation: aerosol for external use 5%: containers 58 g or 116 g

Active ingredient: Dexpanthenol (Dexpanthenol)

The remedy for burns for children and adults contains dexpanthenol - pantothenate provitamin. Upon contact with the skin, it turns into vitamin B5, which stimulates the regeneration of the epidermis and deep layers of the skin. https://skinperfect.ru/ozhog/sprei

Bepanthen

Bepanthen plus burn spray, bayer

The main active ingredients of the spray are dexpanthenol and chlorhexidine digluconate.

Bepanthen Spray is a colorless, transparent liquid with a slight odor, intended for the treatment of minor skin lesions. Due to its composition, the drug plays a key role in the metabolism of each cell. It helps in the healing of lesions and the formation of new epithelium, has a bactericidal effect against gram-positive bacteria and is well tolerated.

Bepanthenplus Spray is effective and easy to use for the treatment of skin lesions where there is a high risk of infection.

The spray is used externally: it is sprayed up to 3 times a day on inflamed skin or on a cleaned wound. Recommended for use by adults, adolescents and children according to indications.

As with any medication, Bepanthen should be used with caution as repeated use may cause skin irritation. In very rare cases, the spray causes allergic reactions. All possible side effects are described in the instructions.

A spray (RF patent 2674 445) for external use for healing wounds, burns and ulcers is proposed, containing lidocaine, bakelite lacquer, polyvinyl butyral and rosin as active substances, and dibutyl phthalate, castor oil and ethyl alcohol as auxiliary substances, and the components in the spray are in a certain ratio, in %. EFFECT: invention provides impermeability to bacteria, high gas permeability, mechanical properties that provide comfort at the time of application, fixation and protection of the wound from further damage, as well as the absence of injury at the time of removal of the coating.

Spray composition:

bakelite varnish - 1.65%,

polyvinyl butyral - 9.7%,

rosin - 0.85%,

lidocaine - 10%

and excipients:

dibutyl phthalate - 3.5%,

castor oil - 1.75%,

ethyl alcohol - 72.55%.

Due to the special form of release in the form of a spray, fast and effective gluing of the wound surface is ensured, preventing microorganisms from entering the wound. The addition of an anesthetic in the form of lidocaine to the drug provides an analgesic effect. It is supposed to use the drug in the field to protect military personnel from infection of wounds received during the exercises.

The pharmacological action of the spray is an insulating, wound-healing, antiseptic, hemostatic agent. The spray is a clear or slightly turbid liquid from light yellow to reddish in color.

How to use the spray - externally. Spray the drug directly onto the damaged surface, capturing the surrounding healthy tissue. After 2 minutes, a thin, elastic film is formed, which is firmly held on the surface of the skin.

We believe that the disadvantage of this composition of the spray is the absence of a pharmacologically active substance with a wound healing effect.

The lidocaine contained in the spray has only an analgesic effect. There are no data on the rate of wound healing.

The aim of the invention is to create a spray for the treatment of wounds containing derivatives of acexamic acid. This goal is achieved by the development of the composition and technology of obtaining a spray for the treatment of burns based on compounds 1 and 2, as well as biological tests of the obtained spray.

Disclosure of the invention.

Example 1

800.0 ml of ethanol and 25.0 g of hydroxypropyl methylcellulose (KlucelLF) are poured into a three-necked flask of 2.0 or 1.5 l, equipped with a stirrer, thermometer and reflux condenser, thoroughly mixed until complete dissolution.

50.0 g of kollidon VA 64 are added to the resulting solution, stirred until complete dissolution. Then load 50.0 g of compound 1, stir until complete dissolution, add 10.0 g of ionol, stir and add 1.0 g of compound 2.

The mixture is stirred for 10.0-15.0 minutes and ethanol is added to 1000.0 ml.

Get 1.0 l of spray.

Example 2

Analogously to example 1, from 25.0 g of Klucel LF, 50.0 g of kollidone VA 64, 10.0 g of ionol, 50 g of compound 1.1.0 g of compound 2, 1.0 l of spray is obtained.

Example 3

Analogously to example 1, from 25.0 g of Klucel LF, 50.0 g of kollidon VA 64, 10.0 g of ionol, 50 g of compound 1 and 1.0 g of compound 2, 1.0 l of spray is obtained. Specific gravity 0.84 g / cm ³

The results of the analysis of the obtained samples of the spray.

Studies of the pharmacological activity of the aerosol dosage form, sprays (examples 1, 2 and 3) are presented in the following examples.

Example 4

4.1. Wound healing activity of sprays (examples 1, 2 and 3), in a model of a linear skin wound in rats

Wound healing activity was studied in experiments on white non-linear rats of both sexes (30 individuals of both sexes weighing 180-220 g, obtained from the nursery of the Andreevka branch of the Federal State Budgetary Institution of Science of the NCBMT of the FMBA of Russia) when applying a spray to the wound surface starting from the first day after the reproduction of a linear wound in for 10 days, three times a day.

Wound healing activity was studied on the model of a linear skin wound in rats by measuring the rate of healing of the wound defect, determining the strength of the emerging scar. A linear wound defect 5 cm long was reproduced on the hairless skin of the back of rats anesthetized with urethane (800-850 mg/kg, intraperitoneally) of both sexes by dissection of both the skin and subcutaneous adipose tissue, followed by suturing it, in accordance with the well-known description (Methodological recommendations for Studying the specific activity of drugs for regenerative medicine / A.M. Dygai, G.N. Zyuzkov, V.V. Zhdanov et al. - Guidelines for preclinical study of drugs. Mironov A.N. - Moscow: GrifiK, 2012. - P. 776-787; Murthy S., Gantam M.K., Shalini G., Purohit V., Sharma H., Goel R.K. Evaluation of in vivo wound healing activity of Bacopamonniera on different wound model in rats // Bio. Mea. Res. Int. - 2013. - Vol. 2103: art. ID 972028. doi: 10.1155/2013/972028).

The results of the study of wound healing activity of sprays (example 1 2 and 3) on the model of a linear skin wound in rats are presented in table. 5.

Presented in table. 5 data indicate that local spraying of sprays, example 1, 2 and 3, over the surface of the wound three times a day for 10 days leads to a statistically significant increase in the healing rate of the wound defect of the skin, when compared with the control group, which in all cases is accompanied by an increase the strength of the scar connection (according to the tear strength index).

Thus, the topical application of sprays (example 4, 5 and 6) leads to earlier healing of a linear wound in the skin of rats and the formation of a more durable scar at the site of the formation of the wound defect.

Example 5

4.2. Wound healing activity of sprays, (example 4 5 and 6), on the model of a planar skin wound in rats

The wound-healing activity of sprays (example 1, 2 and 3) was studied in experiments on white non-linear rats of both sexes (30 individuals of both sexes weighing 180-220 g, obtained from the nursery of the Andreevka branch of the FGBUN NCBMT FMBA of Russia) when applying sprays, ( example 1, 2 and 3) on the wound surface starting from the first day after the reproduction of a linear wound for 14 days, three times a day.

The regenerative activity was studied on the model of a plane wound of the skin of the back in rats by measuring the area of the wound and the resulting scar.

A planar wound defect with an area of about 500 mm3 was reproduced on the hairless skin of the back of rats anesthetized with urethane (800-850 mg/kg, intraperitoneally) of both sexes by excising an area of skin and subcutaneous adipose tissue with a radius of approximately 125 mm, in accordance with the well-known description (Methodological recommendations on the study of the specific activity of drugs for regenerative medicine) A.M. Dygai, G.N. Zyuzkov, V.V. Zhdanov et al. - Guidelines for the preclinical study of drugs. Sub-red. A.N. Mironov. - M.: GrifiK, 2012. - P. 776-787; Murthy S., Gantam M.K., Shalini G., Purohit V., Sharma H., Goel R.K. Evaluation of in vivo wound healing activity of Bacopamonniera on different wound model in rats // Bio. Med. Res. Int. - 2013. - Vol. 2103: art. ID 972028. doi:10.1155/2013/972028) The skin defect remained open throughout the entire observation period.

The results of the study of the regenerative activity of sprays, (example 1, 2 and 3), on the model of a planar skin wound in rats are presented in table. 6.

Presented in table. The data in Table 6 show that a fourteen-day topical spray application, (example 1, 2 and 3), three times a day, is accompanied by a statistically significant increase in the healing rate of a surgically formed skin defect when compared with the control. Against the background of the use of sprays, example 1, 2 and 3, a more delicate scar is formed than in the control.

Thus, in contrast to the control, topical application of sprays (example 1, 2 and 3) leads to faster healing of a planar skin wound defect.

Example 6

4.3. Anti-inflammatory activity of an aerosol dosage form, sprays (example 1, 2 and 3), on a model of a planar skin wound in rats

The anti-inflammatory activity of the aerosol dosage form, sprays (example 1, 2 and 3), was studied in experiments on white non-linear rats of both sexes (30 individuals of both sexes weighing 180-220 g, obtained from the nursery of the Andreevka branch of the FGBUN NTSBMT FMBA of Russia).

When applying sprays (example 1, 2 and 3), on the wound surface starting from the first day after the reproduction of a linear wound for 14 days, three times a day.

Anti-inflammatory activity was studied on a model of a plane wound of the skin of the back in rats by measuring the tissue concentration of cytokines - interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) in the tissues of the wound. A planar wound defect with an area of about 500 mm3 was reproduced as described in example 5.

On the 8th day of the experiment, the granulation tissue from the wound was removed under urethane (800-850 mg/kg, intraperitoneally) anesthesia, homogenized, and the concentration of IL-10 and TNF-alpha was determined by quantitative enzyme immunoassay (Valentin M.-A., Ma S., Zhao A. , Legay F., and Avrameas A. Validation of immunoassay for protein biomarkers: bioanalytical study plan implementation to support pre-clinical and clinical studies // Journal of Pharmaceutical and Biomedical Analysis, 2011. - Vol. 55, No. 5. - P . 869-877).

The results of the study of the anti-inflammatory activity of sprays (example 1, 2 and 3), on the model of a planar skin wound in rats are presented in table. 7.

Of the presented in table. 7 data found that local fourteen-day spraying (example 1, 2 and 3) three times a day, is accompanied by a statistically significant increase in the level of IL-10 in the granulation tissue covering the skin wound, formed surgically, and a proportional decrease in the concentration of TNF-alpha, when compared with control.

Thus, in contrast to the control, the topical application of sprays (example 1, 2 and 3) is accompanied by the suppression of the formation of a local inflammatory reaction.

The studies were carried out in accordance with the ethical requirements for working with experimental animals (“Rules for carrying out work using experimental animals” (Order of the Ministry of Health of the USSR No. 755 of August 12, 1987), Federal Law “On the Protection of Animals from Cruelty” of January 1, 1997 Moscow, Order of the Ministry of Health of the Russian Federation dated April 1, 2016 No. 199n "On approval of the rules of good laboratory practice", GOST 33216-2014 "Guidelines for keeping and caring for laboratory animals. Rules for keeping and caring for laboratory rodents and rabbits" ( entered into force on July 1, 2016) and approved by the Bioethical Commission.

Compared with the control, the use of the dosage form of sprays (example 1, 2 and 3) allows you to accelerate the healing of linear and planar skin wounds with the formation of a cosmetically less rough scar at the site of damage without the formation of a local inflammatory reaction.

Claims (2)

1. Spray for the treatment of linear and planar wounds, containing as active ingredients: 2-ethyl-6-methyl-hydroxypyridinium N-acetyl-6-aminohexanoate, silver N-acetyl-6-aminohexanoate and ionol in the amount of 5.0, 0 .1 and 1.0 wt.%, respectively. 2. A method for the treatment of linear and planar wounds, including applying the spray according to claim 1 to the wound surface 3 times a day.