RU2372925C2 - Sapropel balsamic liniment - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to agents for treating wounds, ulcers and decubitus ulcers. A balsamic liniment for treating wounds, ulcers and decubitus ulcers is based on sapropel tar, xeroform, aerosil, sapropel oil taken in a certain relation.

EFFECT: liniment described above shows improved clinical effectiveness in relation to wounds, ulcers and decubitus ulcers.

7 tbl, 1 ex

Description

The invention relates to medicine, in particular to the manufacture of medicinal substances, and can be used in the treatment of wounds, ulcers, bedsores, etc.

Vishnevsky's balsamic liniment is known, containing birch tar - 3.0 g, xeroform - 3.0 g, aerosil - 5.0 g, castor oil - 89.0 g or cod or fish oil purified for external use (Balsamic liniment ( according to Vishnevsky), pharmacopeia article FS42 1093-97).

Famous balsamic liniment Vishnevsky containing tar birch tar - 3.0 g, xeroform - 3.0 g, fish oil up to 100.0 g (Furina EA, Bredneva ND Prescription drugs. Under the author's conditional name. Reference manual for the improvement of doctors. Tyumen: TMI, 1993).

Liniment has antiseptic and bactericidal properties, but despite extensive clinical experience using tar-like composites for the treatment of wounds and diseases of other etiologies, they include polycyclic aromatic hydrocarbons (PAHs), in particular benz-alpha-pyrene (BAP), which have certain concentrations and with prolonged use of a carcinogenic effect. It is known that prolonged use of wood tar and ointments based on it in humans can cause skin cancer (Shusterov G.G., 1926), headache, and kidney damage.

The objective of the invention is to eliminate the known disadvantage, as well as expanding the range of natural raw materials.

The problem is solved in that the balsamic liniment for the treatment of wounds, ulcers, bedsores based on tar, containing xeroform, aerosil, contains sapropel tar, additionally contains sapropel oil in the following ratio, wt.%:

Sapropel tar 1.0-3.0 Xeroform 2.0-4.0 Aerosil 2.0-4.0 Sapropelic oil up to 100.0

In order to expand the range of natural raw materials, the authors use sibropels of Siborganiki LLC, which are a paste-like mass from dark brown to beige or gray. The physical and chemical characteristics of sapropels are quite complex, but any sapropel deposit contains organic matter, water, mineral particles and gas. The mineral part is represented by macroelements (silicon, calcium, compounds of iron, magnesium, potassium, aluminum, sulfur, phosphorus, etc.) and almost all microelements.

Microorganisms that populate sapropel deposits synthesize vitamins, enzymes, amino acids, antibiotics, hormone-like and other biologically active substances: estrone, estroil, estradiol. Sapropels contain vitamins of groups B, E, C, D, P, carotenoids, as well as enzymes: catalase, peroxidase, reductase, protease.

It was found that the multicomponent composition of sapropel plays an important role in obtaining tar and oil, which are then used to obtain therapeutic compositions that play a restoring role in the physiological processes of a living organism.

Tar from sapropel of Omsk Irtysh from a local manufacturer is promising for isolated use in medicine as a medicine of the dermatotropic series, as well as for inclusion in various composites, as does not contain benz-alpha-pyrene (BAP) (application of the same authors No. 2006103052, decision on the grant of a patent dated 04/12/07).

Sapropel tar is a product of distillation of sapropel at a temperature of 100-500 ° C and is a phenol-containing dark oily liquid with a relative density of 0.925-0.950 with a specific odor. It mixes well with ether, chloroform, dissolves in solutions of caustic alkalis.

When the tar content is less than 1.0 wt.% In the liniment, the composition will not have sufficient healing properties, the tar content of the tar more than 3 wt.% Has not been investigated.

According to OST 91500.05.001-00, sapropel oil was tested for authenticity, transparency, solubility, refractive index, acid number, saponification number, iodine number, pH of aqueous extraction, etc. In all respects, it meets the requirements of the International and State Pharmacopoeia.

Sapropel oil is a clear, thick and dense (0.916 in JP X1Y) liquid, yellowish-green to light brown in color (depending on the deposits) with a pleasant odor, easily soluble in acetone, chloroform, insoluble in water, acidity <0.2 , the saponification number is less than 200. The oil is obtained by two-phase extraction of sapropels, where 90% ethyl alcohol (water-alcohol phase) and soybean oil (oil phase) are used as extractants. The extraction is carried out at a temperature of 60 ° C and a stirrer speed of 3500 rpm, for 25 minutes The ratio of raw oil remained constant, equal to 1:10, and the ratio of alcohol to oil was 1: 1, 1: 2, 1: 5, 1:10.

Xeroform C12H5Bi ₃ Br ₆ O ₆ is an integral part of the liniment and is an astringent antiseptic. A liniment with a xeroform content of less than 2.0 wt.% Will not have sufficient antiseptic properties, and a xeroform content of more than 4 wt.% Is undesirable from the point of view of the bismuth content in it.

Aerosil is a substance that hardens the ointment base, a hardener. The content of Aerosil less than 2 wt.% Makes the ointment base liquid, unstable and heterogeneous. An aerosil content of more than 4 wt.% Complicates the application of the ointment to the skin due to its hardness.

In liniment with the option "fish oil" it is completely replaced by sapropel oil.

The method of obtaining liniment balsamic sapropelic

Table 1 Components examples Wt% one 2 3 Sapropel tar one 2 3 Xeroform 2 3 four Aerosil 2 3 four Sapopel oil 95 92 89

Xeroform is thoroughly ground in a mortar with a small amount of sapropel oil. When grinding, add sapropel tar and in a few steps the rest of the oil. The resulting mass is sealed with aerosil. Liniment will have the most effective effect on the wound, burn, pressure sores in the composition of example 2. The boundary indicators of the mixture are less effective.

In the example below, the antiseptic properties of sapropelic tar was performed according to the “disc” method, which is currently standard (Medical Microbiology. Edited by O. L. Pozdeev. M, 2004, p. 178-179). Studies were performed on the following cultures: Sandida albicans, Staphylococcus aureus, Esherichia coli. The antimicrobial activity of antiseptics was studied on solid nutrient media, followed by cultivation under aerobic conditions at 37 ° C for 48 hours. In example 1, disks from filter paper were impregnated with birch tar, in example 2 - sapropel tar. After incubation, the diameter (in mm) of the zone of inhibition of growth of microorganisms of each of the bacterial test cultures was determined.

The obtained data on the diameters of the zone of growth inhibition are listed in table 2.

table 2 Antimicrobial activity indicators of antiseptics No. Component Staph. aureus Esherichia coli Candida albicans one. Tar birch 10 8 7 2. Sapropel tar fifteen fourteen 12

The table shows that sapropelic tar may be of interest as an active substance for the preparation of antiseptic dosage forms for animals and humans for external use, for example, ointments, emulsions, suspensions, gels.

EXAMPLE. Model of a scalped wound.

The studies were carried out in the experimental department of the Central Scientific Research Laboratory GOU VPO OmGMA on white mice according to the standard method. The experimental animals were divided into 3 groups: in the first group (15 animals), the wound surface was treated with a composition containing high-temperature sapropel fractions (tar fractions), in the second group (the same number of animals), the wound was treated with sapropel oil daily, in the third - the wound was treated daily levomikolem ("reference method"). The stages of the study included observation of animals in terms: 3, 8, 14 and 21 days of the post-traumatic period.

The study of protein metabolism revealed the following changes in the dynamics of wound healing:

Table 3 The dynamics of the level of total serum protein of experimental animals with a scalped wound model using various components of sapropel Group 3 days 8 day 14 days 21 days 1 group - fractions
sapropel tar 67.8 ± 2.2 57.9 ± 1.4 73.4 ± 1.5 74.9 ± 5.9 Group 2 - fractions of sapropel oil 63.9 ± 3 70.3 ± 3 71.2 ± 3.1 79 ± 5.8 3 group - levomikol 82.5 68.7 62.3 ± 6.2 75.9 ± 4.9

As can be seen from the table, the most rapid restoration of the level of total serum protein occurs when using sapropelic oil.

Table 4 Dynamics of carbohydrate metabolism in the blood serum of experimental animals with a scalped wound model Group of animals 3 days 8 day 14 days 21 days 1 group - fraction Glucose, 8.91 ± 3.1 6.56 ± 0.6 9.42 ± 0.5 7.59 ± 2.2 sapropelic Mmol / l tar Lactate 7.29 ± 1.6 5.63 ± 0.6 4.93 ± 0.6 6.21 ± 1.4 Mmol / l 2 group - oil Glucose, 6.67 ± 1.4 7.86 ± 1.2 8.66 ± 3.1 6.1 ± 1.5 sapropelic Mmol / l Lactate 5.31 ± 0.33 6.97 ± 1.5 6.71 ± 2.2 6.9 ± 1.1 Mmol / l 3rd group - Glucose, 7.42 6.95 8.95 ± 3.1 5.63 ± 0.15 levomikol Mmol / l Lactate 5.47 11.39 4.65 ± 0.5 9.8 ± 1.2 Mmol / l

Table 5 The dynamics of lipid metabolism in the blood serum of experimental animals with a scalped wound model Group Indicators (in mol / l) 3 days 8 day 14 days 21 days 1 group - Triglycerides 0.59 ± 0.1 0.44 ± 0.1 0.33 ± 0.1 0.51 ± 0.1 fractions Cholesterol tar common 1.63 ± 0.1 1.17 ± 0.22 1.75 ± 0.2 2.04 ± 0.4 saprop 1-cholesterol 0.93 ± 0.1 0.81 ± 0.05 1.31 ± 0.07 1.12 ± 0.1 left B-cholesterol 0.43 ± 0.08 0.215 ± 0.1 0.32 ± 0.2 n / a 2 group - Triglycerides 0.44 ± 0.05 0.69 ± 0.4 0.8 ± 0.7 0.62 ± 0.2 oil Cholesterol sapropel. common 1.61 ± 0.3 1.72 ± 0.24 1.56 ± 0.1 1.9 ± 0.6 1-cholesterol 0.84 ± 0.06 0.98 ± 0.07 1.15 ± 0.05 1.1 ± 0.2 B-cholesterol 0.57 ± 0.22 0.43 ± 0.09 0.31 ± 0.3 n / a 3rd group - Triglycerides 0.34 0.53 0.26 ± 0.1 0.57 ± 0.2 levomikol Cholesterol common 2,51 1.71 1.82 ± 0.08 1.2 ± 0.01 1 - cholesterol 1.13 1.09 1.19 ± 0.2 0.89 ± 0.04 B - cholesterol 1.22 0.38 0.49 ± 0.04 n / a

Table 6 The dynamics of the level of serum transaminases of experimental animals with a scalped wound model Group Indicators 3 days 8 day 14 days 21 days 1 group - AsAT, ME / L 236.5 ± 12 211.2 ± 9.8 158.8 ± 4.7 118.9 ± 43.6 tar fractions AlAT, ME / L 38.8 ± 1.8 24.8 ± 4.7 27.8 ± 5.8 88.1 ± 29 2 group AsAT, ME / L 235.7 ± 16 172.5 ± 30.6 175.5 ± 21.8 115.2 ± 23 saprop oil. AlAT, ME / L 48.7 ± 2.8 13.8 ± 9.2 43.3 ± 25.2 75.6 ± 29 3 group AsAT, ME / L 211.5 164.4 157.9 ± 2.2 51.4 ± 24.5 levomikol AlAT, ME / L 43 2,8 93.8 ± 85.4 68.7 ± 1.5

As can be seen from the data presented in table 6, the activity of key enzymes (AsAT and AlAT) was quite high throughout the entire observation period with the external use of both high-temperature fractions and oil extract from sapropel, which reflects the intensity of hepatic metabolism during accelerated (compared with a group using chloramphenicol, including methyluracil and chloramphenicol) healing a skin wound in these groups of animals.

The level of uric acid in blood serum in the dynamics of the study in experimental animals is presented in Table 7. It is known that the level of uric acid as a final product of macroerg metabolism under conditions of inadequate blood supply rises sharply, indirectly indicating the presence of a hypoxic metabolic vector. As can be seen from the table, a low level (in comparison with group 3) of serum uric acid indirectly indicates that accelerated wound healing under the influence of high-temperature fractions of sapropel (tar) and oil extract from sapropel proceeds under conditions of lower catabolism intensity of macroergs.

Table 7 The dynamics of the level of uric acid in blood serum of animals with a model of a scalped wound Group 3 days 8 day 14 days 21 days Group 1 - tar fractions 98.7 ± 15.8 112.6 ± 17.7 165.9 ± 15.7 170 ± 18.1 2 group - sapropel oil 88.8 ± 8.3 153.1 ± 20.1 253.6 ± 34.5 198.1 ± 24.0 3 group - levomikol 80.8 280.5 230.1 329.9

Animal blood tests showed that with daily treatment of the wound with high-temperature sapropel fractions, the number of leukocytes in them one day after applying the wound was 17.7 · 10 ⁹ / l and after increasing on the 5th and 14th days it decreased by the 21st day amounted to 11.9 · 10 ⁹ / l. In this case, wound healing occurred on the 17-20th day. In the second group of animals, when treating the wound with sapropel oil, a smooth decrease in the level of leukocytes from the initial (18.8 · 10 ⁹ / L) was observed by 17.6% (5th day), by 49.0% (14th day). By the end of the study period, their level was 11.0 · 10 ⁹ / L. The wound healing time was 14 days. In the control series of experiments using levomikol, the number of leukocytes by 21 days of the study remained at the initial level (18.0 · 10 ⁹ / l) and the wound healing time was 20-22 days.

The dynamics of changes in the number of lymphocytes using sapropel preparations was different from the control: thus, the number of lymphocytes during treatment of the wounds with sapropel fractions on the 21st day decreased compared to the initial one, and increased in the control. The content of monocytes, eosinophils and basophils increased by the end of the study period. The use of sapropel oil contributes to an earlier effect of normalization of indicators (5-14th day) and acceleration of wound healing in comparison with fractions of sapropel (21st day of treatment) and the data of the control group, where normalization of indicators by the end of the study was not detected. Extracts from sapropel with prolonged use had a stimulating effect, increasing the number of red blood cells and the level of hemoglobin, monocytes, eosinophils and basophils in the peripheral blood of experimental animals with a model of skin scalped wounds, while there were no allergic, local skin and marked negative general clinical reactions.

Observation of experimental animals in various groups showed that when using the composition of the proposed liniment, the scalped wound is released from the scab 2-3 days earlier than when using the prototype (Vishnevsky liniment).

Based on the above particular characteristics of sapropel tar and sapropel oil, described by separate indicators of the effect on the body, we can conclude that liniment as a whole has a more pronounced dermatotropic therapeutic effect.

Claims (1)

Balsamic liniment for the treatment of wounds, ulcers, bedsores based on tar, containing xeroform, Aerosil, contains sapropel tar, additionally contains sapropel oil in the following ratio, wt.%:
Tar sapropelic 1.0-3.0 Xeroform 2.0-4.0 Aerosil 2.0-4.0 Sapropel oil up to 100.0