RU2478380C1 - Medicinal syrup and method of its preparation - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of medicine, in particular to pharmacological preparations, namely: to medicinal syrups. Essence of the invention lies in the following: claimed is syrup with polydihydroxyphenylenethiosulfonate sodium (hypoxenum) based on xilite with the following component ratio: xilite - 70%, polydihydroxyphenylenethiosulfonate sodium - 5%, multifruit concentrate - 7%, purified water - the remaining part, as well as method of said syrup obtaining, which includes swelling of xilite in water for 30 minutes, heating of mixture to 60-70%, boiling for 10 minutes with removal of formed foam, cooling mixture to 95-97єC, adding polydihydroxyphenylenethiosulfonate sodium and multifruit concentrate, re-boiling syrup for 15 minutes with removal of foam, bringing syrup in weight to 100% with purified water, processing mixture with ultra sound at frequency 25 kHz for 30 seconds by means of waveconductor-concentrator, providing amplitude of fluctuation of radiated medium particles up to 7 mcm, further colation and filtration of final syrup.

EFFECT: claimed syrup possesses antihypoxant properties and can be applied in complex treatment and prevention of chronic diseases, including in pediatrics, as it possesses pleasant sour-sweet taste and fruit fragrance.

2 cl, 3 dwg, 5 tbl, 1 ex

Description

The invention relates to medicine, in particular to pharmacological agents, namely to medicinal syrups.

Syrups (Sirupi) are concentrated solutions of sugar in water and fermented berry juices, as well as their mixtures with solutions of medicinal substances (drugs), tinctures and extracts. Syrups are indispensable components of medicines for children, the main purpose of which is to correct the unpleasant taste of some drugs. [Gryadunova G.P. Syrups: guidelines / G.P. Gryadunova, V.Ya. Lebedenko, N.S. Sorokina; under the editorship of A.I. Tenzova. - M. - 1994. - 20 p.].

Medicines include syrups containing certain drugs, for example, marshmallow syrup, rhubarb, licorice, pertussin, Doctor Mom, etc. [Gryadunova G.P. Syrups: guidelines / G.P. Gryadunova, V.Ya. Lebedenko, N.S. Sorokina; under the editorship of A.I. Tenzova. - M. -1994. - 20 p.].

The closest in technical essence to the proposed syrup is Ambroxol, which includes a sweetener (food sorbitol), flavor and odor flavor (aromatic food essence), medicine (Ambroxol hydrochloride), sodium benzoate, propylene glycol, citric acid, 5.5- trisubstituted sodium citrate aqueous, ethyl alcohol, purified water with the following ratio of components: sorbitol - 56%, aromatic food essence - 0.23%, ambroxol hydrochloride - 0.3%, sodium benzoate - 0.5%, propylene glycol - 9.5%, acid lemon - 0.92%, sodium trisubstituted 5.5-aqueous citrate - 0.18%, ethyl alcohol 90% - 8.4%, purified water - the rest [RF Patent No. 2169557 dated 06/27/2001].

Sorbitol syrup is prepared according to the following technology: 0.56 kg of sorbitol is weighed into the boiler and poured with purified water. The mixture is left for 30 minutes, during which time sorbitol becomes loose and dissolves more easily. Then steam is supplied to the boiler and the mixture is heated to 60-70 ° C. Sorbitol can be added in parts to heated water with continuous stirring. After complete dissolution of sorbitol, the syrup should boil 2 times, the resulting foam (protein and mucous substances) is removed with a slotted spoon. Cooking the syrup should be short: heating the mixture to dissolve sugar - 35-40 minutes and boiling the mixture twice - 20-25 minutes. This eliminates the caramelization of sugar. A sign of syrup readiness is the absence of foam formation. The finished syrup is filtered and filtered while hot [RF Patent No. 2169557 dated 06/27/2001; Chueshov V.I. Industrial Technology of Drugs: A Textbook for Pharmacy Students. universities / V.I. Chueshov // Kh .: MTK-Kniga, 2002. - Vol. 2. - S. 66-67].

According to the State Register of Medicines of the Russian Federation, medicinal syrups with antioxidants and antihypoxants are not registered.

The creation of medicinal substances that protect biomacromolecules from the damaging effects of free radicals and unoxidized products of lipid peroxidation (POL) is one of the urgent problems of modern pharmacology.

The objective of the invention is to expand the range of medicinal syrups by creating a syrup with antihypoxic and antioxidant substances for the complex treatment and prevention of chronic diseases.

The essence of the invention lies in the fact that the proposed syrup with sodium salt of polyhydroxyphenylene thiosulfonic acid (hypoxene) based on xylitol in the following ratio of components: xylitol - 70%, sodium salt of polyhydroxyphenylene thiosulfonic acid - 5%, multifruit concentrate - 7%, purified water - the rest.

A method of obtaining a medicinal syrup includes swelling xylitol in water for 30 minutes, heating the mixture to 60-70 ° C, boiling for 10 minutes to remove the resulting foam, cooling the mixture to 95-97 ° C, adding the sodium salt of polyhydroxyphenylene thiosulfonic acid and concentrate multifruit, repeated boiling of the syrup for 15 minutes with removal of foam, bringing the syrup by weight to 100% purified water, sonication of the mixture at a frequency of 25 kHz for 30 seconds with a waveguide-hub, providing an amplitude of vibration particles of the irradiated medium to 7 microns, further filtering and filtering the finished syrup.

The inclusion of the sodium salt of polyhydroxyphenylene thiosulfonic acid in the syrup gives it antihypoxic properties and increases the body's resistance to oxygen deficiency.

The proposed concentration of the sodium salt of polyhydroxyphenylene thiosulfonic acid (hypoxene) in the syrup is due to the need to achieve the most appropriate frequency of use of the drug to provide the desired therapeutic dosage of the sodium salt of polyhydroxyphenylene thiosulfonic acid (0.25 g 3 times a day).

The medicinal syrup of this composition is a homogeneous viscous liquid of black color, sweet taste and has a pronounced antihypoxic effect, due to the presence of the sodium salt of polyhydroxyphenylene thiosulfonic acid and xylitol, which provides the most pronounced pharmacological effect of the dosage form (LF), and the introduction of a multifruit concentrate gives a pleasant sour-sweet taste and fruity aroma, drowning out the specific smell of the sodium salt of polyhydroxyphenylene thiosulfonic acid s.

Ultrasound treatment of LF with a frequency of 25 kHz for 30 seconds by a waveguide-concentrator with an oscillation amplitude of particles of the irradiated medium up to 7 μm ensures homogenization of the mixture (since the sodium salt of polyhydroxyphenylene thiosulfonic acid is difficult to dissolve in purified water) while maintaining the quantitative and qualitative composition of the sodium salt of polyhydroxy sulfenophenylene chloride microbiological purity of syrup. In a conventional ultrasonic wave, the amplitude of the oscillations is hundredths of a micron.

A syrup of the proposed composition is prepared as follows.

Example. To make 1 kg of syrup, 0.7 kg of xylitol is weighed into the boiler, which is 70% of the total mass, and pour purified water, leaving it for 30 minutes until swelling, then steam is fed into the boiler and the mixture is heated to 60-70 ° C. After complete dissolution of xylitol, the mixture is boiled for 10 minutes, removing the resulting foam, then the syrup is cooled to 95-97 ° С, 0.05 kg (5% of the total mass) of sodium salt of polyhydroxyphenylene thiosulfonic acid and 0.07 kg of multifruit concentrate are added to it ( pineapple - 30%, mango - 20%, orange - 20%, apple - 5%, lemon - 5%, pear - 5%, mandarin - 5%, banana - 5%, passion fruit - 5% (Israel), then the mixture boil again for 15 minutes, removing the resulting foam, bring the mass of purified water to 100%, treat the syrup with ultrasound for 30 seconds at a frequency of 25 kHz p Using a medical-type installation URSK-7n with a waveguide-hub, which provides the amplitude of oscillations of particles of the irradiated medium at the tip of the waveguide up to 7 μm, then the syrup is filtered through a metal mesh, filtered using a suction filter (or Druck filter, KHNHFI filter, etc. ) and pack 100 ml of syrup into dry, odorless, clean bottles of orange glass with a screw cap.

The finished syrup of the proposed composition was evaluated by the following indicators: description, density, pH, microbiological purity, the quantitative content of the sodium salt of polyhydroxyphenylene thiosulfonic acid (hypoxene) in the syrup, the time of release of the sodium salt of polyhydroxyphenylene thiosulfonic acid from LF (biopharmaceutical studies). Next, the syrup was stored in a tightly sealed container made of dark glass for two years and checked after 3, 6, 9, 12, 18 and 24 months according to the following indicators: description, density, pH, microbiological purity, quantitative content of sodium salt of polyhydroxyphenylene thiosulfonic acid in syrup. In the table. 1 presents the results of a study of the stability of a syrup with sodium salt of polyhydroxyphenylene thiosulfonic acid during long-term storage.

Density was determined using a pycnometer according to the GF XI method; pH was determined using a Seven Multi Mettler Toledo pH meter. [State Pharmacopoeia of the USSR, eleventh edition // Issue. 1 General methods of analysis. - M .: Medicine, 1987].

In the study of LF for microbiological purity, the total microbial number (TMP) in 1.0 g of syrup was determined by plating the dilution of LF 1:10 on storage media by the method of GF XI. The detection of fungi, S. aureus, E. coil, and P. aeroginosa was carried out by transfer to Saburo, Endo, vitelline salt agar, peptone agar. [State Pharmacopoeia of the USSR, eleventh edition // Issue. 1 General methods of analysis. - M .: Medicine, 1987].

The syrup was also tested for microbiological purity when stored open. For this, the syrup with sodium salt of polyhydroxyphenylene thiosulfonic acid was stored in a dark glass bottle with an open lid, the bottles were periodically closed and opened again after a while. Samples were taken for plating on culture media after 5, 10, 15, 20 and 30 days. In the study of LF for microbiological purity, the total microbial number (TMP) in 1.0 g of syrup was determined by plating the dilution of LF 1:10 on storage media by the method of GF XI. The detection of fungi, S. aureus, E. coli, P. aeroginosa was carried out by transfer to Saburo, Endo accumulation media, vitelline salt agar, peptone agar. [State Pharmacopoeia of the USSR, eleventh edition // Issue. 1 General methods of analysis. - M .: Medicine, 1987]. The test results are shown in table 2.

Biopharmaceutical studies were carried out by in vitro dialysis using a dialysis film as a semipermeable membrane; UV spectrophotometry was used in the wavelength range 200-380 nm (shoulder 303-306 nm).

A portion of the syrup in an amount of 1.0 g was applied to the dialysis film and placed in 50.0 ml of dialysis medium. Dialysis medium - 0.1 M solution of hydrochloric acid (50.0 ml), since LF is intended for absorption in the stomach. Dialysis was carried out in a thermostat at a temperature of 37 ° C ± 0.5 ° C. 3.0 ml samples were taken after 15 minutes; 30 minutes; one; 2; 2.5 and 3 hours. The selected sample was placed in a 50.0 ml flask and adjusted to the mark with purified water.

The optical density of the samples was measured using purified water as a comparison solution. In parallel, the optical density of the control sample was measured (syrup without hypoxene). The sodium salt of polyhydroxyphenylene thiosulfonic acid in the dialysate was calculated taking into account the dilution of PCO according to the following formula:

where X is the content of sodium salt of polyhydroxyphenylene thiosulfonic acid

(hypoxene) in 50.0 ml of dialysate;

D _syrup - the average optical density of the dilution of the syrup;

D _basis - the average optical density of the dilution of the basis;

D _PCO is the average optical density of the dilution of the working standard sample.

Next, the percentage of sodium salt of polyhydroxyphenylene thiosulfonic acid in 50.0 ml of dialysate was calculated, which shows the degree of release of the substance from the dosage form. In the table. 3 presents the results of biopharmaceutical studies of freshly prepared syrup with sodium salt of polyhydroxyphenylene thiosulfonic acid; in FIG. 1 is a graph of the time dependence of the degree of release of the sodium salt of polyhydroxyphenylene thiosulfonic acid from the syrup.

In addition, the syrup was checked for stability of the degree of release of the sodium salt of polyhydroxyphenylene thiosulfonic acid from the LF after 3, 6, 9, 12, 18, and 24 months of storage (Table 4). In FIG. Figure 2 shows a plot of the degree of release of the sodium salt of polyhydroxyphenylene thiosulfonic acid from syrup versus time during storage.

The antihypoxic activity of the syrup with the sodium salt of polyhydroxyphenylene thiosulfonic acid was checked. Acute normobaric hypoxic hypoxia with hypercapnia was simulated on laboratory animals by placing them in a pressurized chamber. The studies were carried out as follows: for 1 hour, two rats with an average weight of 200 g (control and experimental) were administered prophylactically oral syrup base (without sodium salt of polyhydroxyphenylene thiosulfonic acid) and syrup with sodium salt of polyhydroxyphenylene thiosulfonic acid, respectively. Syrup with sodium salt of polyhydroxyphenylene thiosulfonic acid was administered in an amount corresponding to a dosage of 50 mg / kg, and the base of the syrup was also introduced in the same amount. 1 hour after the administration of rats, they were placed in pharmacy barrels made of transparent glass with a ground glass stopper with a volume of 2500 ml, the animal lifespan in minutes was recorded [Tentsova A.I. Modern directions of pharmaceutical research // Modern aspects of the creation and study of dosage forms. - Sat All-Union. scientific conf. - Baku, 1984. - C.3-9; Fisenko V.P. Guidelines for the experimental (preclinical) study of new pharmacological substances. - M .: "Remedium", 2000].

For each study, 10 tests were performed, the results were statistically processed. In the table. 5 presents the results of pharmacological studies of syrup with sodium salt of polyhydroxyphenylene thiosulfonic acid.

From the table. Figure 5 shows that the average life span of the experimental rats is 1.5 times greater than the control values.

Thus, the sodium salt of polyhydroxyphenylene thiosulfonic acid in the syrup of the proposed composition exhibits antihypoxic activity at a dose of 50 mg / kg with a single prophylactic administration in the model of normobaric hypoxia with hypercapnia.

The proposed flow chart for the production of drug syrup with the sodium salt of polyhydroxyphenylene thiosulfonic acid is shown in FIG. 3.

The proposed method for the manufacture of syrup is selected experimentally and is optimal for obtaining a medicinal syrup based on hypoxene with the best antihypoxic properties.

As can be seen from the description, the proposed medicinal syrup has antihypoxic properties and can find application in the complex treatment and prevention of chronic diseases accompanied by hypoxia, including pediatrics.

table 2 Medicinal syrup Sampling time intervals Microbiological purity 5 days Category 1 10 days Category 1 15 days Category 3 20 days Category 3 30 days Category 3

Table 3 Observation periods The degree of release of hypoxene from syrup (%) 15 minutes 12.98 ± 0.33 30 minutes 22.82 ± 0.85 1 hour 38.35 ± 0.89 2 hours 86.20 ± 0.61 2.5 hours 94.45 ± 0.30 3 hours 99.95 ± 0.14

Table 4 Medicinal syrup Sampling time intervals The degree of release of hypoxene from syrup (%) after 3 months of storage after 6 months of storage after 9 months of storage after 12 months of storage after 18 months of storage after 24 months of storage 15 minutes 15.15 ± 0.52 22.49 ± 0.44 25.09 ± 0.69 18.45 ± 0.72 20.17 ± 0.49 24.48 ± 0.36 30 minutes 28.12 ± 0.39 32.28 ± 1.17 41.52 ± 1.14 32.66 ± 0.86 35.24 ± 0.58 38.59 ± 0.33 1 hour 44.90 ± 0.55 58.79 ± 0.75 56.95 ± 1.19 57.21 ± 0.48 56.88 ± 0.21 57.00 ± 0.25 2 hours 76.14 ± 0.33 81.75 ± 0.80 76.25 ± 0.27 77.15 ± 1.28 79.18 ± 0.35 74.66 ± 0.41 2.5 hours 93.00 ± 0.44 91.22 ± 0.49 92.14 ± 0.55 90.15 ± 0.48 93.16 ± 0.27 90.89 ± 0.57 3 hours 99.77 ± 0.42 99.98 ± 0.38 99.40 ± 0.74 99.80 ± 0.30 99.85 ± 0.39 99.82 ± 0.35

Table 5 Medicinal syrup Experience number The life expectancy of animals, min Control rat Experienced rat one 79 115 2 77 119 3 77 118 four 79 120 5 76 118 6 79 120 7 78 118 8 75 121 9 74 119 10 76 121 The average time for the results of 10 experiments 77.0 ± 1.0 119.0 ± 1.0 Note: the life expectancy of control rats and experimental rats significantly differ from each other (p <0.05).

Claims (2)

1. Medicinal syrup, including sweetener, flavor and odor flavoring agent, medicine and purified water, characterized in that it additionally contains sodium salt of polyhydroxyphenylenethiosulfonic acid (hypoxene), xylitol as a sweetener and multifruit concentrate as a flavor and odor flavoring agent in the following ratio components: xylitol - 70%; sodium salt of polyhydroxyphenylene thiosulfonic acid (hypoxene) - 5%; multifruit concentrate - 7%, which contains pineapple - 30%, mango - 20%, orange - 20%, apple - 5%, lemon - 5%, pear - 5%, mandarin - 5%, banana - 5%, passion fruit - 5%; purified water - up to 100%. 2. A method of manufacturing a medicinal syrup according to claim 1, including swelling the sweetener in purified water for 30 minutes, heating the mixture to 60-70 ° C, followed by boiling for 10 minutes after dissolving the sweetener, removing the resulting foam, filtering and filtering the finished syrup characterized in that after boiling the mixture, the syrup is cooled to 95-97 ° C, polyhydroxyphenylene thiosulfonic acid sodium salt (hypoxene) is added to it and the multifruit concentrate is boiled again for 15 minutes, removing the foam, then the mixture is brought to the mass of water purified to 100% and the syrup is treated with ultrasound at a frequency of 25 kHz for 30 s with an oscillation amplitude of particles of the irradiated medium up to 7 μm at the tip of the waveguide-hub.

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