Ginger extract-based preparation

FIELD: pharmaceutical industry, in particular production of stable ginger extract-based preparation.

SUBSTANCE: claimed preparation contains dry ginger extract and polyvinyl pyrrolidone as stabilizing ancillary agent in specific ratio. Method for production of said preparation includes extraction of ground ginger roots to produce liquid extract solution, solution concentration to produce viscous extract, dilution of viscous extract, addition of polyvinyl pyrrolidone solution as stabilizing ancillary agent to natural extract, stripping and drying. Also disclosed is galenia preparation, containing abovementioned stabilized ginger extract-based preparation and additional ancillary agents such as silicium dioxide, maltodextrin, magnesium stearate, cellulose or carboxymethylstarch. Such preparation is useful in treatment of dyspeptic disorders, naupthia sypptoms, as antiemetic agent, antidiabetic agent, etc. Stable ginger extract-based preparation obtained by abovementioned method and galena preparation based on the same are characterized by constant ratio of [6]-gingerol to [6]-shogaol.

EFFECT: stable therapeutic agent based on ginger extract.

13 cl, 2 dwg, 7 tbl, 4 ex

 

This invention relates to preparations of ginger that meet the characteristics of a stable preparation of the extract for a longer period of time, i.e. within the period of time of up to 18 months or more, as well as to methods of their preparation. The present invention also describes a stable galenic formulations containing preparations of ginger, such as capsules, tablets, coated tablets, as well as their application.

Ginger (Zingiber officinale), which has for centuries been known for healing properties and properties spice plants, acquiring in recent years increasingly important in the pharmaceutical industry and in the field of food additives. Drugs from the rhizomes of ginger (Rhizoma zingiberis) - as a medicinal powder by itself and separated from his extracts, used for the treatment of diarrhoeal diseases and symptoms of sea sickness (described in the literature review in Langner, E., et al.: Balance 1, 5-16, October 1997). The Commission E pre-existing Federal Health Committee also took into account a number of pharmacological studies and published a positive monograph "Zingiberis rhizoma" (Bundesanzeiger Nr.85 from 05.05.1988 and Bundesanzeiger Nr.50 from 13.03.1990). The average daily dose is 2-4, Essential oil and particularly pungent substances (Ginga the rolls, shogaol and dehydrogenation), considered as ingredients, are also responsible for the effectiveness. Commercially available preparations, the relevant monograph, currently represent medicinal powders and tea mixture with a dose of 2-4 g corresponding to the monograph, and the relevant extracts are obtained using mixtures of alcohol/water. On the other hand, the extracts prepared using supercritical CO2not covered by the monograph of the Commission E due to insufficiently proven efficacy and tolerance. However, they are common to the food industry as spice extracts.

Among burning substances the bulk quantitatively represent gingerly. Shogaol and dehydrogenation represented in much smaller quantities as they are biogenetically only by-products of Generalov (Schuhbaum, H., Franz, G.: Zeitschrift für Phytotherapie 21, 203-209, 2000).

Gingerale have side chains of different lengths (6, 8 and 10 atoms, shown in figure 1), where [6]-gingerol is a main component (Falch, W., Reichling, J., Sailer, R.: Dtsch. Apotheker Zeitung 137, 47-60). In addition Generalov also described the pharmacological effects [6]-shogaol (Suekawa, M. et al.: J. Pharm. Dyn. 7, 836-848, 1984).

It is known that sogoli formed from gingerols during storage of whole and, in particular, and melcena roots of ginger (Zhang, X. et al.: J. Food Science, 59, 1338-1343, 1994). Permanent conversion of gingerols in sogoli during storage is also described for the crushed root ginger (Steinegger, E., Stucki, K.: Pharm. Acta. Helv.57, 3, 1982), see the Mechanism As in figure 2.

It also describes that the content of gingerols in spirit aqueous extracts prepared decreases in the direction of education Sokolov (thesis Germer, S., University of Regensburg, 1996); see Mechanism B in figure 2. Relation [6]-gingerol to [6]-shogaol, thus, represents a qualitatively suitable parameter for assessing the preparation of ginger extracts and their further processing (Feistel, W., Gaedcke, F. et al.: Analytische Charakterisirung von Ingwer-Zubereitungen, Poster-Nr. P19, Finzelberg-Symposium 2000).

In order to guarantee a stable therapeutic quality drugs ginger, must be ensured reproducible quality. The main prerequisite for this is that the transformation of gingerols in sogoli if possible, should be prevented (constant relation [6]-gingerol to [6]-shogaol).

Thus, it is desirable to provide preparations of ginger, which prevented known reaction rearrangement of gingerols and provided a constant ratio gingerol/shogaol. As stable in the pharmaceutical sense, to pharmaceutically acceptable ingredients include drugs for which change is the obsession of the ingredients during the validity period is not more than ± 10%.

From DE 19859499 A1 it is known that ginger extracts can be stabilized by adding at least one herbal auxiliary agent, so that the contents of burning substances (here we mean only the amount of the basic substance 6-gingerol and its decomposition product 6-shogaol) decreases during the period of time of up to 18 months, up to 10%. As auxiliary agents in this mentioned oils, semi-solid triglycerides, fatty acids and fatty alcohols. This may reduce the content of 6-gingerol only up to 20%, while in the natural extract of ginger 6-gingerol decomposed in the same conditions to approximately 32%.

Parameter content pungent substances (denoted as the sum of 6-gingerol and its decomposition product 6-shogaol), thus, remains naturally constant (the transformation is shown in figure 2), which is unsuitable to say about the quality. Significant here is only the ratio of 6-gingerol to 6-shogaol in combination with the contents of burning substances (sum of 6-, 8 - and 10-gingerol and 6-shogaol).

Lipophilic auxiliary agents mentioned in the description of the patent application DE 19859499 A1, contribute to the fact that gingerale will be stabilized physically by increasing the viscosity. However, the disadvantage is t is, used in herbal auxiliary agents (oils, fats) do not have the ability to prevent dehydration of the underlying loss of stability of gingerale. In addition, States that in accordance with this method are obtained oily, viscous preparations, which generally may be made only in soft gelatin capsules, as it is also known for lipophilic viscous extracts of ginger (Ginger spissa) or oil extracts of ginger (Ginger oleosa). Stable solid herbal form for the introduction of oil extracts of ginger, such as tablets, capsules or coated tablets, for the moment not known.

Thus, one task of the present invention is to provide preparations of ginger, which ensure long-term stability of gingerols and relationships gingerol/shogaol, and which, moreover, can be processed in a simple way to obtain various solid stable form for injection.

This task in accordance with this invention is solved by the preparation of ginger extract containing ginger extract, which contains at least one stabilizing auxiliary agent from the group of substances, exciting the protons. It has been unexpectedly discovered that by adding such in the substances largely prevented decomposition reaction of Generalov, so that they get the drugs ginger, who for many months have essentially stable content [6]-gingerol, as well as the constant ratio of [6]-gingerol to [6]-shogaol. Thus, the protonation of the ingredients of the extract, which is the cause dehydration and thus the decomposition of these substances is prevented, because an exciting protons substance absorbs available free protons or reflects the attack of available free protons.

Preparations of ginger extract in this invention are not oil, as this is known to currently available drugs. On the contrary, they are dry, bulk drugs extract, which can also be directly subjected to pelletizing. Moreover, in comparison with commercially available preparations of ginger temperature sensitivity of Generalov significantly reduced. As a result, the stress test preparations of ginger extract in this invention at 40°showed that there is no change in the content of gingerol (see table 1).

Table 1

comparative stability of drug extract of ginger for 4 weeks at a temperature of 40°C. (In parentheses are the specific ratio 6-gingerol to 6-Shog the Olu, presents as a criterion of stability.)
The invention Sample 9101.1100The prior art (DE 19859499 A1)
The initial value for the 6-gingerolto 2.29% (2,6:1)8,11% (2,0:1)
4 weeks at 40°2,23% (2,6:1)to 6.80% (1,3:1)

Especially preferred are such auxiliary agents from the group of substances, exciting the protons, in which the substance is an exciting protons suitable for quantitative re-release of burning substances from complex extract auxiliary agent, which thus used auxiliary agents do not prevent the release of pharmaceutically acceptable ingredients from the mold for injection (no formation of irreversible connections enable). As a result, provided a stable pharmaceutical quality.

Particularly preferred auxiliary agents for stabilization of the groups of substances, exciting the protons are polyvinylpyrrolidone (kollidon, polymeric N-vinylpyrrolidone), which simultaneously provide a quantitative release of acceptable ingredients.

The use of polyvinylpyrrolidone as auxiliary agents for the preparation of galenic forms known on p is ateenyi many years. They are used as herbal tearing agents and are, in particular, to increase the solubility of sparingly soluble drugs. Also polyvinylpyrrolidone used for plant extracts. So, from the application WO 99/32130 know the use of polyvinylpyrrolidone to improve the release of valuable ingredients of the dry extracts of medicinal plants. Using semisolid or solid complex from plant extract and excipient in which valuable constituents of the extract are distributed microdisperse so that their release and the degree and speed can be standardized at a high level. Polyvinylpyrrolidone, derivatives of cellulose or starch mentioned in addition to other substances, such as glycols, polivinilatsetata and polyvinylglycol contribute to improved solubility in water and, due to the increased surface area, improved release of the ingredients. As in other cases, polyvinylpyrrolidone use due to their effect on the physical properties of dry extracts of medicinal plants when used in accordance with the application WO 99/32130.

Unexpectedly, in the framework of the present invention has been shown that in the case of preparations of ginger extract polyvinylpyrrolidone, in addition, have the indicate also the chemical effect and function of stabilizing the image on the ingredients. Due to the fact that they act as pathological, they prevent the protonation and subsequent as a result of this dehydration of gingerale. This chemical principle applies during the process of preparation of the extract of ginger (in liquid medium), as well as during long-term storage (in solid form).

In particular, all pharmaceutical auxiliary agents, having in its composition nitrogen, thanks to the free electron pair belong to the group of substances, exciting the protons. Substances such as zeolites or cyclic oligosaccharides, in which the reaction of protons with generally prevented by forming inclusion complex extract auxiliary agent may also act through entrainment of the proton. These auxiliary agents actually turned out to be acceptable in terms of quality to stabilize the preparations of ginger, but at the same time, they do not guarantee the quantitative suitability burning substances ginger, as, for example, it can polyvinylpyrrolidone.

In particular, it is known that cyclodextrins, for example β-cyclodextrin, have the ability to spatially separate the ingredients of ginger that you want to stabilize, from the extraction of the matrix and thereby prevent their protonation. This principle is used, for example, m is Siroki pungent taste of ginger, for example, in chewable tablets (described in DE-Gbm. 20102817). However, this inclusion complex does not have the ability afterwards to quantitatively release again burning substances (partially irreversible inclusion complexes). This auxiliary agent, thus, not suitable for medical use of drugs of ginger.

In order to ensure stabilization, the quantitative ratio of the auxiliary agent, exciting the protons, the natural extract is preferably more than 50%, in particular it is in the range from 60 to 90%, with particularly favorable is the value of approximately 75%.

Known to date methods preparation of extract of ginger, thus, was also unfavorable, because the content of these pharmaceutically acceptable ingredients, such as burning substances and essential oil are reduced in the resulting extract.

Thus, another objective of the present invention is to provide a method of preparation of stable preparations of ginger, which is additionally supported the transition of the maximum possible number of pharmaceutically acceptable substances in the preparation of the extract.

This task is solved in accordance with this invention through the m offers fashion, at which stage of the process is carried out at a temperature of up to 45°C. Under such mild temperatures reduced the processes that lead to the reduction of the content of the ingredients of ginger and, therefore, receive preparations of ginger, with a larger fraction of the pharmaceutically acceptable ingredients. Especially preferred temperature range was the range of from 35 to 45°because these temperatures, on the one hand, high enough to ensure that the appropriate speed of the extraction process, and on the other hand, low enough to ensure a gentle process monitoring.

Such soft control process ensures that the ratio [6]-gingerol to [6]-shogaol, which, as mentioned in the introduction, is a qualitatively suitable parameter for assessing the preparation of ginger extracts and their further processing, significantly higher and more stable compared with traditional cooking processes.

At least one stabilizing auxiliary agent from the group of substances exciting protons, preferably used in the method of preparation. Applying at least one substance from the group of substances exciting protons, minimizes decomposition reactions ingredients of ginger, called the by protonation.

Extracting agents used for the extraction of rhizomes of ginger, preferably belong to the group of alcohols having C1-C4 carbon atoms, the group of aliphatic ketones having a C1-C5 carbon atoms, the group of aliphatic hydrocarbons to the group of mixtures of water and alcohol solvents from 1 to 99% (vol./vol.), to the group of mixtures of water and ketones from 1 to 99% (vol./vol.), or are pure water or supercritical gas, such as carbon dioxide.

Initial extraction of Rhizoma zingiberis using a mixture, preferably a polar extracting agent provides, through soft exhaustive filtration, the highest possible output pharmaceutically acceptable ingredients, such as, for example, burning substances or essential oils. Thus, get the medicine, having 10-12-fold excess solvent, at a temperature of up to 45°C. Obtained eluate unite and carefully concentrated in vacuo. The obtained viscous extracts was adjusted using ethanol, until the dry matter content of approximately 20%. Diluted ethanol solutions are well mixed by stirring at room temperature with the same pure ethanol solutions of auxiliary stabilizing agents, with a share of dry substance of about 10%. Then in vacuum at a temperature of receipt is 35-45° To perform a soft concentration of this mixture. This soft cooking ensures obtaining viscous extract without reducing the content of burning substances and/or essential oils. Final drying is carried out, in turn gently in the chamber with vacuum drying at 35-45°adding dry auxiliary agents, such as, for example, maltodextrins, or silica. Get a dry, free-flowing stable preparation of extract of ginger.

Cooking method preferably includes the steps:

- soft primary extraction of the crushed root ginger,

- soft further concentration, in particular, by extraction using supercritical carbon dioxide

- adding at least one stabilizing auxiliary agent to the liquid extract containing 20% dry matter,

- final soft evaporation and drying of the thus obtained preparation of the extract.

Further soft concentrating and drying have the advantage that the resulting preparations of ginger are free-flowing powder, which at the same time, essentially free from impurities of aflatoxins.

Extraction using supercritical carbon dioxide, thus acatalasemia favorable form of concentration, at the same time is also possible in other ways, such as, for example, column chromatography or liquid - liquid methods.

Finally, the present invention is to provide herbal medicines, in which due to the fact that they contain stable preparations of ginger, can be achieved by appropriate quality for even a longer period and for different loads.

This problem was solved by offering herbal medicines that contain drugs of ginger extract in this invention, where these drugs may additionally contain conventional auxiliary agents, such as silica, maltodextrins, stearates of magnesium, cellulose or carboximetilkrahmala. Such herbal medicines preferably proposed for treatment in any of the forms of capsules, tablets and coated tablets.

In accordance with this invention for the first time it became possible to obtain a dry stable preparation of extract of ginger. From DE 19859499 follows that the extract obtained Econoline-water method, which is transferred to the dry preparation of the extract of ginger by adsorbing galenic auxiliary agents (silicon dioxide), shows a decrease in the content of 6-gingerol approximately 37% after only 2 months. Accordingly what about the first time in accordance with this invention it has become possible to extrude in tablet preparations of ginger without losing stability. Because the stability of drug extract of ginger, in addition, significantly increased in accordance with the present invention can also provide a much greater shelf life compared to unstabilized galenovye drugs.

Preparations of ginger extract in this invention can be applied, in particular, as a drug for the treatment of diarrhoeal diseases, the symptoms of sea sickness, as an antiemetic, as an antidiabetic agent, an anaesthetic, treatment vomiting associated with pregnancy or caused by chemotherapy, atherosclerosis, diseases of the rheumatic type, or as a suitable nutritional supplements.

Additional advantages and embodiments can be seen in the Examples and tests described below. Figure 1 shows the most important representatives of burning substances at the root of the ginger, and figure 2 shows the decomposition reaction on the example of the main pungent compounds 6-gingerol.

Comparative example 1 - Sample: non-stabilized viscous extract ginger extract Zingiberis e rhiz. spir. spiss.).

50 kg of a rhizome zingiberis crushed and sieved to obtain pieces of 6-8 mm, fully filtered using 500 kg of 96%ethanol (vol./vol.). The temperature of the product does not exceed 45°C. Filtered analnye fractions are combined and carefully concentrated in vacuo at 45° With the formation of viscous extracts.

Example 2 - example B: Preparation of ginger, stable Calligonum 25

45,5 g the source of the extract obtained similarly to the Sample (extract Zingiberis e rhiz. spir. spiss. with a solids content of 33%), corresponds to 15 g of dry extract is diluted with the use of >99% ethanol to the dry matter content of 20%. Within 15 minutes perform intensive mixing Solution 1.

of 99.75 g kollidon diluted under stirring with the use of >99% ethanol to the dry matter content of 10%. Within 30 minutes to carry out intensive mixing of the Solution 2.

Both solutions integrate by parts with stirring at room temperature, the resulting red-brown transparent solution. Stirring is carried out for 30 minutes and the mixture was carefully concentrated on a rotary evaporator at a maximum temperature of the water bath 45°C. the resulting preparation of the extract evaporated to until it has no solvent, and dried in a drying chamber at 45°With vacuum. As an auxiliary agent add 5%silicon dioxide.

For examples a and B in each case, the content of pungent substances (6-, 8-, 10-gingerol and 6-shogaol) was controlled using high-performance liquid chromatography (HPLC) at the beginning (= initial value) and after 11 and 15 of the month is. Thus, data were obtained, are shown in Table 2 below:

Table 2

The stability of the preparations according to this invention compared with the unstabilized source extract of A. the Contents of burning substances in preparations of extract B and C was calculated to compare with the natural extract.
SampleAnalytical parametersThe beginning (initial value)11 months15 months
AndThe contents of burning substances20%15,9%15,4%
The ratio of 6-gingerol: 6-shogaol(3,4:1)(1:1)(0,7:1)
BThe contents of burning substances15,6%15,6%15,6%
The ratio of 6-gingerol: 6-shogaol(1,9:1)(1,9:1)(1,9:1)

(In parentheses are the ratio of 6-gingerol to 6-shogaol, represented as a value measure rearrangements occurred).

It was shown that for non-stabilized extract And the content of burning substances is reduced by almost 25%, and in particular, the ratio of 6-gingerol to 6-sougou also designed for people who is; on the other hand, stable preparation of extract B according to this invention has a significantly improved stability in regard to the content of burning substances and, in particular, relations 6-gingerol to 6-sougou, which is a constant within analytical error.

In addition, stability tests carried out on samples with different percentages of natural extract, to obtain the following results (table 3).

2,7:1
Table 3

The stability data of the drug extract of ginger Calligonum 25 as an auxiliary agent (at room temperature).
Time [months]
13% natural extractStart61218Changes
The contents of burning substances [%]3,143,123,163,09-1,9%*
6-gingerol: 6-shogaol4,9:14,5:14,5:14,6:1constantly*
6-gingerol [%]1,821,781,781,79-1,7%*
6-shogaol [%]0,370,400,400,38+2,5%*
Time [months]
30% natural extractStart2816Changes
The contents of burning substances [%]4,344,294,194,18was 3.7%
6-gingerol: 6-shogaol2,6:12,6:12,6:12,6:1stable
6-gingerol [%]to 2.292,162,122,18-4,8%
6-shogaol [%]0,880,830,820,81-8,0%
Time [months]
49% of the share of natural extractStart2816Changes
The contents of burning substances [%]9,008,808,77a total of 8.74-2,9%
6-gingerol: 6-shogaol2,8:12,8:12,9:1stable
6-gingerol [%]4,77to 4.684,584,67of-2.1%
6-shogaol [%]1,781,671,611,66-6,7%
*Relative changes of some components partially situated within the range of analytical error and are therefore the boundary.

It is shown that preparty extract of ginger also remain stable for a long period of time. In contrast, raw ginger extract demonstrates characteristics are presented in Table 4:

Table 4

The stability data for non-stabilized extract of ginger; monitoring for 8 weeks proved to be unsuitable in light of these results.
Time [week]
Original extractStart8Changes
The contents of burning11,29,020%
substances [%]
RatioChange
6-gingerol: 6-shogaol3,1:10,8:1ratio
opposite;
regrouping

In addition, stable preparations of ginger with various percentages of natural extract were investigated in relation to their thermal stability in a period of 6 months. The results are presented in Table 5 (In parentheses are the ratio of 6-gingerol to 6-shogaol, represented as a value measure rearrangements occurred).

Table 5

Results content of hot substances during the stress test stable welding temperature, avannah preparations of ginger extract for 6 months.
The designation of the sample TemperatureThe contents of burning substancesThe ratio of 6-gingerol: 6-shogaolAppearance after 6 months
The initial valueis in 2 weeksthe value after 6 months
30%natural extract (Spir. Spiss.)
25°C/60% rF4,34 (2,6:1)4.26 deaths (2,6:1)4,19 (2,6:1)powder
30°C/60% rFto 4.23 (2,6:1)4,17 (2,5:1)powder
40°C/75% rF4,18 (2,4:1)4,17 (2.2 to 1)slightly lumpy
49%natural extract (Spir. Spiss.)
25°C/60% rF9,00 (2,7:1)8,59 (2,7:1)8,70 (2,8:1)lumpy
30°C/60% rF8,44 (2,6:1)8,61 (2,7:1)baked
40°C/75% rF8,61 (2,7:1)8,24 (2,3:1)baked
49%-h the th natural extract (Oleosum *)
25°C/60% rF4,90 (6,1:1)4,94 (5,9:1)4,94 (5,8:1)powder
30°C/60% rF4,95 (5,8:1)of 5.05 (5,7:1)powder
40°C/75% rF4,81 (5,6:1)4,91 (4,6:1)slightly lumpy
*prepared by extraction using supercritical carbon dioxide

Changes in stability within the range from ±5 to ±10% are considered stable in the pharmaceutical sense, to pharmaceutically acceptable ingredients. Regardless of the actual tests at elevated temperature and humidity in accordance with ICH guidelines, it was found that even visually the drug with an increased share of natural extract of 49%, exhibits a tendency to form lumps. This picture by increasing the temperature still increases. Thus, this drug extract is not suitable for testing in a long stress test. The contents of burning substances remains within ±5%bounds for the other two preparations of ginger, even at elevated temperatures up to values on the I 6 months. Thus, ensured successful stabilization.

Temperature stability of the raw extract and stabilized preparation of the extract of ginger is presented in Table 6 below:

Table 6

The test temperature stability within 24 hours (raw extract in comparison with stabilized extract).
TemperatureExtract Zingiberis e rhiz. spir. spiss. Natural extract, unstabilizedPreparation of extract of ginger, stable Calligonum 25. The share of natural extract of 10.5% (Specific figures calculated by the share of natural extract)
The amount of 6-, 8 - and 10-gingerolThe amount of 6-, 8 - and 10-gingerol
Room temperature13,3%13,3%
40°13,2%13,2%
50°13,2%13,2%
60°12,3%13,1%
70°11,5%12,2%
The ratio of 6-gingerol/6-shogaolThe ratio of 6-gingerol/6-shogaol
Room temperaturethe 1.7:1the 1.7:1
40°the 1.7:1the 1.7:1
50°of 1.6:1of 1.6:1
60°1,4:1of 1.6:1
70°1,2:11,4:1

These results demonstrate that stable preparation of the extract even at elevated temperatures has significantly improved the stability properties compared with the properties of conventional unstabilized extracts of ginger. This is confirmed by a lower tendency to decomposition of gingerols and smaller reductions in the ratio of 6-gingerol/6-shogaol. Accordingly, it is shown that temperature to 40-50°are not problematic. Even while checked unstabilized soft ginger extract maintains short-term stress in this temperature range, therefore, can be deduced maximum thermal load for soft primary extraction approximately 45°C. a Known temperature for extraction of ginger roots are in the range of from room temperature to 90°and to the last value in the extracts was not described no quality loss (Govindarajan, V.S.: Crit. Rev. Food. Sci. Nutr. 17, 189-258, 1982). However, recently, the facts confirm that the conditions of extraction >50°common to extract and on an industrial scale, thus, lead to the loss of burning substances and, consequently, to pharmaceutically substandard extract even during the initial extraction of the roots of ginger.

The test results generally show that the preparations of the extract according to this invention remain stable over a long period of time up to 18 months or more. Suddenly they are also significantly more thermally stable in comparison with the untreated extracts. Temperature limit to a maximum of 45°can be set for soft control process for preparing extracts of ginger, especially for primary extraction, which was carried out without addition of stabilizing auxiliary agent. Thus, the process proceeds gently and completely (high output pharmaceutically acceptable ingredients). It is also preferable to further control the cooking process of the preparation of the extract of ginger in accordance with this invention to use temperature up to 45°because thereby can be reduced decomposition or reduction of the content of pharmaceutically acceptable substances.

Extraction using supercritical carbon dioxide is an equally maketemperature processing. The combination of the first is knogo extract, the obtained ethanol/water solution (viscous extract), and its subsequent extraction using supercritical carbon dioxide leads to ginger, who greatly enriched burning substances and essential oil. At the same time coextrusion components of the extract, which is not relevant in terms of efficiency, mostly removed, and further the content is reduced.

The output of these paired stages of the method, the primary extraction and extraction of CO2approximately only 2-3%based on the amount of drugs that corresponds to the native against the drug-extract (OLE) approximately approximately 33-50:1. On the other hand, the usual direct CO2-extraction of a rhizome zingiberis leads to a yield of approximately 4%, which corresponds to the native OLE approximately 25:1.

Add exciting protons substances leads to highly enriched stable preparation of extract of ginger, which is in contrast to a single extraction using organic solvents and direct CO2extraction is a fully pharmaceutically new material.

Example 3

Sticky ginger extract obtained in the same way as described in Comparative example 1 contains 15.8% of the total burning substances and 15.1% of essential oil (n is positive, OLA 12:1). Moreover 10,0 kg viscous extract absorb at 10.0 kg of diatomaceous earth and extracted using 10 kg of C02 per kg of the mixture. Anhydrous yield of oil extract of ginger is 34% based on the used extract. The resulting oily extract (oleosum) ginger contains 22.7% of the total burning substances and 39.0% of essential oil (native OLE 35:1).

15 g of an oily extract of ginger is diluted using >99% ethanol, until the dry matter content of 20%. Stirring is carried out for 30 minutes to obtain a homogeneous solution Solution 1.

85 g Kollidon 25 diluted under stirring >99% ethanol to the dry matter content of 10%. Within 30 minutes to carry out intensive mixing of the Solution 2.

Both solutions integrate by parts with stirring at room temperature, the resulting red-brown transparent solution. Stirring is carried out for 30 minutes and the mixture was carefully concentrated on a rotary evaporator at a maximum temperature of the water bath 45°C. the resulting preparation of extract of ginger evaporated until such time as it has no solvent, and dried in a drying chamber at 45°With vacuum. Get pale yellow granular powder, which contains about 3% pungent substances.

Example 4

Prepare a stabilized preparation of extract of ginger on When the ERU 2, containing 28%natural ginger extract, 63% of Kollidon 25 and 9% of highly dispersed silicon dioxide. Solid form stable preparation of extract of ginger, prepared in accordance with this invention, pressed into a film-coated tablet.

Recipe kernel ginger tablets, coated tablets, mg:

Preparation of extract of ginger303,57
Sodium dodecyl sulphate8,80
Maltodextrin79,23
Silicon dioxide8,80
The cellulose powder11,00
Na-carboximetilkrahmal22,00
Stearic acid6,60
Na-crosscarmelose13,00

Table 7 provides information about the stability of the preparations of ginger and cooked them core tablets with the shell.

Initial
Table 7

Comparative stability of drug extract of ginger and nuclei tablets with sheath for 6 months at 25°With (In parentheses are the specific ratio 6-gingerol to 6-shogaol presented as a measure of stability).
DesignationAnalytical6 months
Sampleoptionsvalue
Used

the drug extract

ginger
the contents of burning substances7,12%7,18%
the ratio of 6-gingerol:6-shogaol(6,9:1)(7,0:1)
Tablet with ginger

shell (67%

preparation of ginger)
the contents of burning substances4,82%4,74%
the ratio of 6-gingerol:6-shogaol(6,9:1)(6,9:1)

Preparation of the extract according to this invention first provides for ginger enriched stable phytopharmacological the agent in solid galenical form also provides a constant therapeutic quality.

Preparation of ginger in the form of hard gelatin capsules

The drug is produced by mixing and filling of hard gelatin capsules consisting of 2 parts, the resulting mixture.

td align="left"> Magnesium stearate
mg/capsule
Preparation of extract of ginger250
Microcrystalline cellulose125
Lactose123
2
500

1. Stable preparation of ginger extract containing ginger extract and at least one stabilizing auxiliary agent, characterized in that it contains dry extract of ginger and polyvinylpyrrolidone as a stabilizing auxiliary agent, with respect to the auxiliary agent to the natural extract is more than 1.5:1.

2. Stable drug extract of ginger according to claim 1, where the ratio of the auxiliary agent to the natural extract is 1.5:1-9:1, and preferably 3:1.

3. Stable drug extract of ginger according to claim 1, having at least 1% burning substances, preferably 3-12% burning substances, the ratio of [6]-gingerol to [6]-shogaol at least 2:1, preferably from 3:1 to 8:1, at least 1% of essential oil, preferably 5-15% (vol./wt.), and essentially free from impurities aflatoxin, which is consistent with the terms of the existing order on the prohibition of the content of aflatoxins.

4. Method of preparation of a stable preparation of a dry extract of ginger, characterized in that it includes the extraction of the crushed root ginger with obtaining liquid extract, concentrating the liquid extract to obtain a viscous extract, a dilution of the viscous extract from the floor is the group of solution, adding to the said solution a solution of polyvinylpyrrolidone as a stabilizing auxiliary agent, and the ratio of the auxiliary agent to the natural extract is more than 1.5:1, and the process of evaporation and drying of the preparation of the extract thus obtained.

5. The method according to claim 4, characterized in that stage of the process is carried out at a temperature not higher than 45°C.

6. The method according to claim 4, characterized in that stage of the method is preferably carried out at a temperature from 35 to 45°C.

7. The method according to claim 4, characterized in that as the extracting agent used is an organic solvent, water or a mixture or supercritical gas, such as carbon dioxide.

8. The method according to claim 7, wherein the extracting agent is an organic solvent selected from the group of alcohols having C1-C4 carbon atoms, from the group of aliphatic ketones having a C1-C5 carbon atoms, from the group of aliphatic hydrocarbons, mixtures of water and alcohol solvents from 1 to 99% (vol./vol.), from the group of mixtures of water and solvents of ketones from 1 to 99% (vol./vol.).

9. The method according to claim 4, characterized in that it further includes concentrating the liquid extract.

10. The method according to claim 4, characterized in that the liquid extract is subjected to concentration and Ni is sustained fashion extraction using supercritical gas, such as carbon dioxide.

11. Herbal preparation containing a stabilized preparation of extract of ginger in one of claims 1 to 3, and additional auxiliary agents, such as silica, maltodextrins, stearates of magnesium, cellulose or carboximetilkrahmala.

12. Herbal preparation according to item 11, presented in any form of capsules, tablets and coated tablets.

13. The use of a stabilized preparation of extract of ginger in one of claims 1 to 3, herbal preparation according to item 11 or 12 for the treatment of diarrhoeal diseases, the symptoms of sea sickness, as an antiemetic, as an antidiabetic agent, an anaesthetic, treatment vomiting associated with pregnancy or caused by chemotherapy, for treatment of diseases of the rheumatic type, or as food additives.



 

Same patents:

FIELD: medicine, endocrinology, pharmaceutical industry.

SUBSTANCE: invention relates to composition possessing the pathogenetic antidiabetic effect that comprises dry aqueous extracts of forest gymnema, tall elecampane and grape bunches taken in the definite ratio. The composition show effective action on all pathogenetic links of insulin-dependent diabetes mellitus: it normalizes blood carbohydrates level in prediabetic period, normalizes carbohydrate metabolism in diabetes mellitus of II type based on regeneration of β-cells in pancreas islet producing insulin, normalizes autoimmune responses in diabetes mellitus of II type and normalizes metabolism in diabetes mellitus based on antioxidants and trace elements. Invention is used in treatment and prophylaxis of diabetes mellitus.

EFFECT: valuable medicinal properties of composition.

6 cl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzoic acid of the formula (I): , wherein represents 0, 1 or 2; R1 represents halogen atom, (C1-C4)-alkyl group that is possibly substituted with one or more fluorine atoms, (C1-C4)-alkoxyl group that is possibly substituted with one or more fluorine atoms and when n represents 2 then substitutes at R1 can be similar or different; R2 represents direct (C2-C7)-alkyl group; R3 represents hydrogen atom (H) or -OCH3; W represents oxygen (O) or sulfur (S) atom, and to its pharmaceutically acceptable salts. Also, invention relates to a pharmaceutical composition used in treatment of hyperlipidemia, dyslipidemia, diabetes mellitus and obesity and comprising derivative of benzoic acid of the formula (I) in mixture with pharmaceutically acceptable adjuvants, excipients and/or carriers. Also, invention relates to using derivative of benzoic acid of the formula (I) for preparing a medicinal agent used in treatment of resistance to insulin. Also, invention relates to a method for synthesis of derivative of benzoic acid of the formula (I) and used for synthesis of intermediate compound of the formula (II) given in the invention description. Invention provides preparing derivatives of benzoic acid representing selective modulators of PPARα.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 14 ex

Glp-1 analogs // 2288232

FIELD: peptides, medicine, pharmacy.

SUBSTANCE: invention relates to novel peptide analogs of glucagons-like peptide-1 and its pharmaceutically acceptable salts that are used in treatment of mammals.

EFFECT: valuable medicinal properties of analogs.

10 cl, 1 tbl, 411 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of pyrimidine of the general formula (I) that possess properties of antagonists to adenosine A2-receptors and can be effective in relieve, for example, of defecation. In compound of the general formula (I) each R1 and R2 represents hydrogen atom; R3 represents hydrogen atom, halogen atom, amino-group, cyano-group, alkyl group comprising 1-6 carbon atoms, alkoxy-group comprising 1-6 carbon atoms, alkenyloxy-group comprising 2-6 carbon atoms, phenyl group that can be substituted with halogen atom, pyridyl group, furyl group or thienyl group; R4 represents pyridyl that can be substituted with a substitute chosen from the group comprising: hydrogen atom, halogen atom, amino-group, mono- or dialkylamino-group, aminoalkylamino-group wherein each has in alkyl residue from 1 to 6 carbon atoms, alkyl group comprising from 1 to 6 carbon atoms that can be substituted with halogen atom, hydroxy-group, amino-group, mono- or dialkylamino-group, alkoxycarbonyl wherein each has in alkyl residue from 1 to 6 carbon atoms, alkoxy-group comprising in alkyl group from 1 to 6 carbon atoms substituted with phenyl or pyridyl, hydroxyalkoxy-group comprising in alkyl residue from 1 to 6 carbon atoms, hydroxycarbonyl, alkoxycarbonyl comprising from 1 to 6 carbon atoms in alkyl residue, alkenyl group comprising from 2 to 6 carbon atoms, alkynyl group comprising from 2 to 6 carbon atoms, piperidinyl group that can be substituted with hydroxyl group, or represents group of the formula (IV): R5 represents phenyl that can be substituted with halogen atom, pyridyl group, thienyl or furyl group.

EFFECT: valuable biological properties of derivatives.

16 cl, 2 tbl, 185 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of 2-cyano-4-fluoropyrrolidine of the formula (I): or its pharmaceutically acceptable salt wherein A represents group of the general formula (II): wherein B represents carbonyl or sulfonyl group; R1 represents (C1-C6)-alkyl that can be optionally substituted with group chosen from the group comprising -OH or atoms of fluorine, chlorine, bromine or iodine, phenyl optionally substituted with -CN or morpholinyl group, or if B represents carbonyl then R1 can mean hydrogen atom; R2 represents (C1-C6)-alkyl optionally substituted with hydroxyl group or hydrogen atom. Compounds of the formula (I) are inhibitors of enzyme dipeptidyl peptidase IV that allows its using in pharmaceutical composition that is designated for treatment of insulin-dependent diabetes mellitus (diabetes of type 1), non-insulin-dependent diabetes mellitus (diabetes of type 2), diseases associated with resistance to insulin or obesity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 8 tbl, 11 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel analogs of fatty acids of the general formula (I): R1-[Xi-CH2]n-COOR2 wherein R1 represents (C6-C24)-alkene with one or more double bond, and/or (C6-C24)-alkyne; R2 represents hydrogen atom or (C1-C4)-alkyl; n represents a whole number from 1 to 12; I represents an uneven number and shows position relatively to COOR2; Xi is chosen independently of one another from the group comprising oxygen (O), sulfur (S) and selenium (se) atom and -CH2 under condition that at least one among Xi is not -CH2 and under condition that if R1 represents alkyne then a carbon-carbon triple bond is located between (ω-1)-carbon atom and (ω-2)-carbon atom, or between (ω-2)-carbon atom and (ω-3)-carbon atom, or between (ω-3)-carbon atom and (ω-4)-carbon atom, and to their salts and complexes. The claimed compounds can be used in treatment and/or prophylaxis of X syndrome, obesity, hypertension, hepatic fatty dystrophy, diabetes mellitus, hyperglycemia, hyperinsulinemia and stenosis. Also, invention relates to methods for preparing novel analogs of fatty acids. Also, invention relates to a nutrient composition comprising indicated analogs of fatty acids and to a method for reducing the total body mass or amount of lipid tissue in humans or animals. Invention provides the development of novel fatty acid analogs-base compositions or methods for suppression of stenosis, restenosis or associated disorders as result of proliferation and mobilization of vessel smooth muscle cells after, for example, traumatic damages of vessels during surgery operation in vessels.

EFFECT: improved preparing method, valuable medicinal properties of analogs.

12 cl, 2 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: the present insulin solution for peroral intake should be applied for treating patients with diabetes mellitus. The suggested insulin solution consists of water and insulin, additionally, it contains sodium chloride at the following ratio of components, weight%: insulin 0.005-0.02, sodium chloride 0.5-1.0, water - up to 100.0. The innovation provides decreased glucose level in blood of animals in case of peroral intake of the solution up to 40% at insulin dosages being about 10 U/kg animal body weight.

EFFECT: higher efficiency.

12 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel lactam compounds of the formula (I) or their pharmaceutically acceptable salts wherein A means phenyl, thienyl, pyridyl, pyrimidinyl, pyrazinyl; R2, R3 and R4 can be similar or different and mean independently of one another hydrogen atom (H), halogen atom, -OH, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -NH2, -NO2, -CF3, phenyl that can comprise substitute(s), benzyloxy-group that can comprise substitute(s), pnehylvinyl, and one among R2, R3 and R4 means -CF3-O- and others mean H; B means phenyl that can comprises substitute(s), monocyclic aliphatic (C3-C8)-ring, dihydropyrane ring; -X- and -Y- xan be similar or different and they mean independently -O-, -NH-, -NR5-, -S-; Z means -CH2-, -NH-; W means -NR1-, -CR8R9- wherein R1 means H; R8 and R9 are similar or different and mean H; wherein R5 represents a linear alkyl group that can comprise substitute(s), (C1-C8)-linear or branched alkoxycarbonyl group, acyl group chosen from formyl group, acyl group comprising (C1-C6)-alkyl, (C1-C6)-alkenyl or (C1-C6)-alkynyl group that can comprise substitute(s), carbamoyl group comprising (C1-C6)-alkyl group at nitrogen atom that can comprise substitutes, sulfonyl group comprising (C1-C6)-alkyl group at sulfur atom that can comprise substitute(s); each among a, b and c represents position of carbon atom under condition that: (i) substitute(s) is chosen from the group comprising halogen atom, -OH, (C1-C6)-alkyl, mercapto-group, (C1-C6)-alkoxy-group, -NO2, -COOH, -CF3, phenyl, -NH2, (C1-C8)-linear or branched alkoxycarbonyl group, (C1-C8)-linear or branched acyl group, (C1-C8)-linear or branched acyloxy-group; (ii) when B represents benzene ring, each among -X- and -Y- represents -NH-, -Z- represents -CH2- and -W- represents -NH- then R2, R3 and R4 can not mean phenyl group, 4-bromophenyl group, 4-hydroxyphenyl group, 4-methoxyphenyl group, 2-hydroxyphenyl group, 3,4-dimethoxyphenyl group or 3-methoxy-4-hydroxyphenyl group. Compounds of the formula (I) show the enhanced capacity for transport of sugar and can be used in pharmaceutical compositions for prophylaxis and/or treatment of diabetes mellitus and diabetic nephropathy.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 21 tbl, 54 ex

FIELD: chemistry of heterocyclic organic compounds, medicine.

SUBSTANCE: invention relates to a novel heterocyclic derivative of the formula (I'): , wherein R1 represents hydrogen atom or (C1-C6)-alkyl; R2 represents-CO-C(R4)=C(R4)-R5 wherein R4 represents hydrogen atom; R5 represents (C2-C8)-alkenyl; R3 represents hydrogen atom or (C1-C4)-alkyl; X represents oxygen atom or sulfur atom; R20 represents phenyl substituted with unsubstituted (C1-C6)-alkyl, (C1-C6)-alkyl substituted with fluorine atom, (C1-C4)-alkoxy-group, phenyl-(C1-C4)-alkoxy-group, hydroxyl group, halogen atom, nitro-group, unsubstituted amino-group or amino-group substituted with (C1-C4)-alkyl; n means a whole number from 1 to 4, or to its pharmaceutically acceptable salt. Also, invention relates to heterocyclic derivative of the formula (I): , wherein R1 represents hydrogen atom or (C1-C6)-alkyl; R2 represents -CO-C(R4)=C(R4)-R5 wherein R4 represents hydrogen atom; R represents (C4-C8)-alkyl or (C2-C8)-alkenyl or -CO-C≡C-R6 wherein R6 represents (C1-C8)-alkyl; R3 represents hydrogen atom or (C1-C4)-alkyl; X represents oxygen atom or sulfur atom; n means a whole number from 1 to 4, or its pharmaceutically acceptable salt. Compounds of the formulas (I') and (I) are effective as a hypoglycemic agent, hypolipidemic agent, agent improving resistance to insulin, therapeutic agent in treatment of diabetes mellitus, therapeutic agent in treatment of diabetes mellitus complications, agents enhancing tolerance to glucose, anti-arteriosclerotic agent, agents against obesity or agent for X syndrome.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 2 tbl, 56 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel condensed cyclopropylpyrrolidines of the formula: wherein x means 0 or 1 and y means 0 or 1 under condition that x means 1 when y means 0, and x means 0 when y means 1; and wherein n means 0 or 1; X means hydrogen atom (H) of group -CN; R1, R2, R3 and R4 are similar or different and chosen independently from H, (C1-C10)-alkyl, (C2-C12)-alkenyl, saturated (C3-C10)-cycloalkyl, saturated (C3-C10)-cycloalkyl-(C1-C10)-alkyl, saturated (C3-C10)-bicycloalkyl, saturated (C3-C10)-tricycloalkyl, hydroxyl-(C1-C10)-alkyl-saturated (C3-C10)-cycloalkyl, (C1-C10)-alkylthio-(C1-C10)-alkyl, (C6-C10)-aryl-(C1-C10)-alkylthio-(C1-C10)-alkyl, (C6-C10)-aryl-(C1-C10)-alkyl, 5- or 6-membered heteroaryl comprising one nitrogen atom (N) or one oxygen atom (O), 5- or 6-membered heteroaryl comprising one atom N condensed with (C6-C10)-aryl ring, 5- or 6-membered heteroaryl comprising one atom N or one atom O, (C1-C10)-alkyl, cycloheteroalkyl that represents (C5-C8)-saturated ring comprising one heteroatom, such as N or O; if necessary, all compounds comprise 1, 2, 3, 4 or 5 groups of substitutes at corresponding carbon atom chosen from halogen atom, (C1-C10)-alkyl, (C2-C12)-alkenyl, hydroxy-group, hydroxy-(C1-C10)-alkyl or cyano-group; R1 and R4 can form in common, if necessary, the group -(CR5R6)m- wherein m means 2-6, and R5 and R6 are similar or different and chosen independently from hydroxy-group, H or (C1-C10)-alkyl including all their stereoisomers; and their pharmaceutically acceptable salt, or prodrug esters and all their stereoisomers. These compound inhibit activity of dipeptidyl peptidase IV that allows their using in pharmaceutical compositions used in treatment of diabetes mellitus of type-2.

EFFECT: valuable medicinal properties of compounds.

20 cl, 6 tbl, 113 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes a novel derivative of 9-(2-diethylaminoethyl)-2-phenylimidazo[1,2-a]benzimidazole, namely its hydrobromide, eliciting properties of antagonist of serotonin 5-HT3-receptors that can be used in therapy of cytotoxic nausea and vomiting. New salt is low toxic and exceeds bemesetron by anti-serotonin activity that is a selective 5-HT3- antagonist.

EFFECT: improved and valuable medicinal properties of derivative.

2 cl, 2 ex

FIELD: medicine, pharmacy.

SUBSTANCE: medicinal formulation possessing an anti-vomiting effect consists of core and envelope dissolving in stomach. Core comprises the following components, wt.-%: domperidone, 2.0-40.0; starch, 7.0-18.5; sodium dodecyl sulfate, 0.1-0.3; polyvinylpyrrolidone, 1.5-4.0; calcium stearate, 0.5-1.2; aerosil, 1.0-3.0; lactose, 49.9-71.0. Envelope comprises the following components, wt.-%: hydroxypropylmethylcellulose, 50.0-70.0; Twin-80, 15.0-25.0, and titanium dioxide, 15.0-25.0. Also, invention describes a method for preparing the medicinal formulation by wet granulation followed by tableting and applying a coating from an aqueous suspension. Deviation of separate tablets by mass is 4.5-5.5%. Tablets possess sufficient strength for qualitative applying the envelope. Decomposition time of tablets is 6-7 min. From 97.8% to 98.4% of domperidone is released from tablet to solution for 45 min.

EFFECT: improved and valuable pharmaceutical properties of medicinal formulation.

3 cl, 1 tbl

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes a composition comprising as active components pyridoxine hydrochloride and doxylamine succinate and a disintegrating agent that provide the following dissolving pattern: 20-90% of the total amount of each component among pyridoxine hydrochloride and doxylamine succinate are dissolved in 5-120 min. The composition is made preferably as a tablet with an enterosoluble envelope. The tablet has a core comprising pyridoxine hydrochloride and doxylamine succinate, and inactive excipients also. The composition is used in treatment of nausea, vomiting being especially in pregnancy. The composition provides rapid and simultaneous release of synergetic pair of indicated active components.

EFFECT: improved and valuable properties of composition.

24 cl, 2 dwg, 9 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: method involves odorizing anti-emetics given to a patient and determining pupil area in the left eye. The area reducing more than by 18% when compared to the initial one, sickness and vomiting is to be predicted.

EFFECT: high accuracy of prognosis.

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of piperazine of the general formula (I): wherein Y represents lower alkylene; R1 represents phenyl substituted with one or two similar or different substitutes taken among a group including lower alkoxy-group, mono- (or di-, or tri-)-halogen-lower)-alkyl, nitro-, amino-, lower alkylamino-, di-(lower)-alkylamino-, lower alkylthio-group,alkylsulfonyl, lower alkylaminosulfonyl, di-(lower)-alkylaminosulfonyl, and pyrrolyl; R2 means phenyl substituted with hydroxy-group at position 3 and with lower alkyl and halogen atom additionally; R3 means hydrogen atom; R4 represents (2,6-dimethylmorpholino)-(lower)-alkyl, (2-methoxymethylmorpholino)-(lower)-alkyl, (3-methoxymethylmorpholino)-(lower)-alkyl. Also, invention relates to their pharmaceutically acceptable salts, to method for their preparing, pharmaceutical composition and a method for vomiting inhibition. Proposed compounds are antagonists of tachykinin and can be used for vomiting inhibition.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

9 cl, 47 ex

FIELD: stomatology.

SUBSTANCE: patient rinses his/her oral cavity with 10-12% sodium chloride solution at 25-40°C for 20-25 min, after which, 10-15 min later, denture is placed into oral cavity.

EFFECT: achieved prolonged reduction in emitting reflex activity.

3 ex

The invention relates to the field of medicine and relates to means for reducing the toxicity of anticancer drugs, characterized in that the pharmacologically active agent used benzamid in doses ranging from 5 to 100 mg/kg

The invention relates to pharmaceutical and veterinary use, namely, to pharmaceutical compositions containing ondansetron, metacin and benzamid

The invention relates to the field of medicine and veterinary medicine and relates to pharmaceutical compositions containing ondansetron and benzamid in amount from 1:4 to 1:200

The invention relates to medicine, namely to surgical gastroenterology, and can be used as a means to prevent vomiting after laparoscopic cholecystectomies

FIELD: pharmaceutical industry.

SUBSTANCE: invention relates to stone oil, extracted from stones of date (Phoenix pubeccens), yellow wood, or walnut containing specific amounts of triglycerides, diglycerides, monoglycerides, sitosterols, and cycloalanosterol. In one embodiment method for extraction of stone oil includes pressing of stones or powered stones, extraction with organic solvent or selectively by using of liquid in above-critical state to produce crude oil; discoloration thereof with adsorbing discoloration agent; dissolution of discolored oil in light ligroin; addition of stoichiometric amount of NaOH under stirring; settlement and aliquation; washing of organic phase with warm water to produce emulsion; addition of acetone to emulsion under stirring; layer separation and producing of oily phase in upper layer; treatment of oily phase to absorb thereof subsequently with neutral aluminum oxide and kaolin; removing after filtration of organic solvent from filtrate in nitrogen atmosphere; oily phase washing with warm water; heating of oily phase in nitrogen atmosphere to dehydrate thereof; and adsorption with neutral aluminum oxide. In another embodiment method for extraction of stone oil includes pressing of stones or powered stones, extraction with organic solvent or selectively by using of liquid in above-critical state to produce crude oil; stirring and heating of crude oil; adding of phosphorus acid to provide full degumming; addition of NaOH or Na2CO3 solution to degummed oil at the same temperature to provide full caustic purification; mixture settlement and aliquation to produce purified oil; washing of purified oil with pure water; addition of adsorbent to washed oil or heating thereof in vacuum to remove water and produce transparent dehydrated oil; discoloration thereof with adsorbing discoloration agent under heating in vacuum and under stirring in nitrogen atmosphere and oil heating up to certain temperature; passing of pure water steam at certain temperature and holding for certain time followed by stopping of purified water steam passing and nitrogen passing under stirring to remove moisture from oil. Pharmaceutical compositions improving of immunological function, increasing serum protein content and tumor growth inhibiting, which contains therapeutically effective amount of stone oil and one or more pharmaceutically acceptable adjuvants also are disclosed.

EFFECT: stone oil effectively improving of immunological function, increasing serum protein content and tumor growth inhibiting.

14 cl, 5 tbl, 11 ex

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