RU2423111C2 - EXTRACTS OF PLANT Chenopodium ambrosioides L, APPLIED IN CHINESE MEDICINE, COMPOSITIONS, INCLUDING SAID EXTRACTS, METHOD OF THEIR OBTAINING AND APPLICATION - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to chemical-pharmaceutical industry, namely to vegetable extracts of plant Chenopodium ambrosioides L., therapeutic compositions with said extracts, methods of obtaining extracts and application of extracts. Extracts of Chenopodium ambrosioides L. and therapeutic compositions, containing them, can be used for production of medications for treatment of gastritis and peptic ulcer, resulting from HP infection.

EFFECT: therapeutic composition possesses expressed positive impact and small side effects.

24 cl, 45 ex, 5 tbl, 7 dwg

Description

FIELD OF THE INVENTION

The present invention relates to plant extracts, in particular extracts of the Chenopodium ambrosioides L. plant used in Chinese medicine, preparations comprising said extracts, and methods for their preparation. The present invention also relates to the use of said extracts in a medicament for the treatment of gastritis or gastric ulcer caused by Helicobacter Pylori (HP).

BACKGROUND OF THE INVENTION

Gastric diseases are common diseases that are common in clinical practice. Ever since Marshall and Warren in Lancet magazine in 1983 (Warren JR, Marshall BJ. Lancet, 1983, 1: 1273 □ 1275) reported that a spiral aerobic bacterium was cultivated on the mucous membrane of the human stomach Called Helicobacter Pylori, or HP for short, and proven to be related to gastritis, the revolutionary changes associated with the recognition of upper respiratory tract diseases were spurred (Xu, Ling, Journal of First Military Medical University, 1995, 15 (4) : 360-361). As a result of deep research, it was gradually revealed that the spiral bacterium is the cause of various gastric diseases. For example, Liu et al suggested that diseases caused by HP infection include gastritis, stomach cancer, stomach lymphoma, duodenal ulcers, etc. (Liu, Junying; Ma, Cailian, Journal of Practical Medical Techniques, 1998, 5 (7): 542-544). It has also been reported that HP can provoke various gastric diseases, such as chronic gastritis, which can subsequently cause stomach ulcers or atrophic gastritis and even develop into gastric cancer (Recent Developments in Science & Technology Abroad, 2003, (4): 44-45).

Based on the aforementioned discovery, studies have begun on drugs against HP, and currently in clinical practice the combination of various chemical drugs is most often used. For example, Mo has been studied 55 groups of drug combinations used abroad (Mo, Jianzhong, Chinese Journal of Digestion, 1995, 15 (3): 164). Huang et al. Reported a combination of omeprazole and antibiotics (Huang, Xuerui; Chang, Heling, Northwest Pharmaceutical Journal, 1998, 13 (1): 33-34). The compositions mentioned above are basically a combination of proton pump inhibitors and antibacterial drugs that can cause serious side effects, and antibiotics can easily provoke drug resistance and dysbiosis.

Chinese medicine is famous for its minor side effects. As a test of anti-HP drugs used in Chinese medicine has shown, Coptis chinensis Franch, Rheum officinale, Cortex Phellodendri., Herba Taraxaci, Polygonum cuspidatum Sieb. et Zucc., A. Sativam L. var. Viviparum Regel, Romulus Cinnamomi., Eugenia caryophyllata Thunb. etc. have high sensitivity (Chen, Zhenmin, Liaoning Journal of Traditional Chinese Medicine, 1995, 22 (10): 472). Chenopodium ambrosioides L. is a whole terrestrial part of the Chenopodium ambrosio des L. plant of the Chenopodiaceae family with a seed spike. The above-mentioned whole ground part contains 0.4-1% of essential oil from Chenopodium ambrosioides L., including ascaridol, r-cimol and other terpenes, such as aritazone, limonene, etc. as the main components; Chenopodium ambrosioides L. has the ability to disperse odor, antihelminthic effect, cleansing and analgesic effect. To date, there is no evidence of the effect of Chenopodium ambrosioides L. in the treatment of gastritis and peptic ulcer caused by HP.

DETAILED DESCRIPTION OF THE INVENTION

The main objective of the present invention is to overcome the disadvantage of drugs known from the prior art and the creation of extracts of Chenopodium ambrosioides L. from readily available raw materials with a pronounced effect and less side effects.

Another objective of the present invention is to provide compositions comprising said extracts.

An additional objective of the present invention is to provide a method for producing extracts and compositions comprising said extracts.

The present invention also provides the use of said extracts and compositions thereof in a medicament for the treatment of gastritis and gastric ulcer caused by HP.

The term "Chenopodium ambrosioides L. essential oil" is also used in the present invention to refer to the Chenopodium ambrosioides L. extract.

To implement the present invention, the following technical solutions.

The extracts of Chenopodium ambrosioides L. proposed in the present invention are analyzed by gas chromatography-mass spectrometry, while the mass spectrum has the following two peaks:

peak 1: retention time is 8.0-9.5 min, fragmentary ions m / e - 121 and 93; and

peak 2: retention time is 9.0-10.0 min, fragmentary ions m / e - 120, 119 and 134.

Preferably, according to gas chromatography-mass spectrometry, the mass spectrum additionally includes the following two peaks:

peak 3: retention time is 10.0-20.5 min, fragmentary ions m / e - 119, 121 and 136; and

peak 4: retention time is 15.0-20.5 min, fragmentary ions m / e - 135, 43 and 97.

More preferably, according to gas chromatography-mass spectrometry, the mass spectrum further includes the following two further peaks:

peak 5: retention time is 5.5-15.5 minutes, fragmentary ions m / e - 93 and 91; and

peak 6: retention time is 12.5-20.0 min, fragmentary ions m / e - 71, 126, 69 and 41.

Analysis conditions:

Sample preparation: Chenopodium ambrosioides L. extracts were dissolved in ethyl acetate;

Gas chromatography conditions:

Chromatographic column: HP-5MS flexible silicate capillary column, 60 m × 0.25 mm × 0.25 μm, containing 5% phenylmethylsiloxane;

Thermal programming: the temperature is increased from 80 ° C to 100 ° C, then to 150 ° C and, finally, to 300 ° C.

Evaporation temperature: 250 ° С;

Carrier gas: high purity helium (99.999%);

Carrier gas mass flow: 1.0 ml / min;

Injected sample volume: 1 μl (ethyl acetate solution);

Breeding Index: 30: 1;

Mass Spectrum Conditions:

Ion source: EI;

The temperature of the ion source: 230 ° C;

The temperature of the quadrupole rods: 150 ° C;

Multiplier Voltage: 1781 V;

Contact interaction surface temperature: 280 ° С;

Mass scan range: 10-550 atomic mass units.

The extracts of Chenopodium ambrosioides L. proposed in the present invention have the following weight contents of the components: α-terpinene - 15-35% and r-cimol - 15-25%.

Preferably, the Chenopodium ambrosioides L. extracts proposed in the present invention have the following weight contents of the components: α-terpinene - 15-35%, r-cimol - 15-25%, ascari-dole - 10-20% and α-terpinolene - 32-40%.

More preferably, the Chenopodium ambrosioides L. extracts proposed in the present invention have the following weight contents of the components: α-terpinene 20-30%, r-cimol 18-22%, ascaridol 12-18% and α-terpinolene 32-35% .

Even more preferably, the Chenopodium ambrosioides L. extracts proposed in the present invention have the following weight contents of the components: α-terpinene 22-25%, r-cimol 19-21%, ascaridol 13-15% and α-terpinolene 32-33 %

More preferably, the Chenopodium ambrosioides L. extracts proposed in the present invention have the following weight contents of the components: α-terpinene - 15-35%, r-cimol - 15-25%, ascaridol - 10-20%, α-terpinolene - 32-40% , γ-terpinene - 0.5-0.7% and limonene - 0.6-0.8%;

or α-terpinene - 15-35%, r-cimol - 15-25%, ascari-dole - 10-20%, α-terpinolene - 32-40% and γ-terpinene - 0.5-0.7%;

or α-terpinene - 15-35%, r-cimol - 15-25%, ascaridol - 10-20%, α-terpinole - 32-40% and limonene - 0.6-0.8%.

Most preferably, the Chenopodium ambrosioides L. extracts proposed in the present invention have the following weight contents of the components: α-terpinene 22-25%, r-cimol 19-21%, ascaridol 13-15%, α-terpinolene 32-33% , γ-terpinene - 0.5-0.6% and limonene - 0.6-0.7%.

The present invention also provides pharmaceutical compositions comprising said extracts and pharmaceutically acceptable adjuvants.

Proposed in the present invention, the medicinal composition may further include another active ingredient. For example, said active ingredient in the pharmaceutical compositions of the present invention is an oil obtained from Adina pilulifera (Lam.) Franch.

The pharmaceutical compositions of the present invention can be formulated in various dosage forms. Said dosage forms include, but are not limited to, capsules, hard capsules, soft capsules (also called gelatin pills), injections, drip solutions, injectable powders, granules, tablets, infusion granules, powders, oral liquids, sugar coated tablets, film coated tablets, enteric-coated tablets, tablets for slow dissolution in the buccal pocket, pills, ointments, dragees, spraying agent, drip pills, disintegrating tablets in the oral cavity, micropills, aerosol b etc.

Said capsules may be ordinary capsules or a self-emulsifying preparation in the form of capsules.

Preferably, the pharmaceutical composition comprising, as an active ingredient, the Chenopodium ambrosioides L. extract of the present invention is in the form of a gelatin pill consisting of the contents and coating material. The mentioned contents of the gelatin pill are Chenopodium ambrosioides L. extract, and vegetable oil.

Said vegetable oil is a pharmaceutically acceptable oil, such as peanut oil, canola oil, tea tree seed oil, etc., from which fatty solid acids are recovered.

The weight ratio of extracts of Chenopodium ambrosioides L. and vegetable oil is 1: (1 ~ 3), preferably 1: (1 ~ 2); most preferably 1: 1.

Said gelatin pill coating material includes gelatin and a softener, wherein the softener is selected from the group consisting of glycerin, xylitol, sorbitol and hydrogenated corn extract; preferably glycerol and xylitol; most preferably glycerol.

Preferably, a dosage form comprising the extracts of Chenopodium ambrosioides L. proposed in the present invention can be formulated as self-emulsifying preparations. The so-called self-emulsifying preparations are the precursor of emulsions and are solid forms or uniform transparent liquid forms including a drug substance, a fatty phase, a surfactant and a secondary surfactant. The main characteristic of self-emulsifying preparations is that in oil-in-water emulsions that spontaneously form in the gastrointestinal tract (GIT) or at ambient temperature (usually related to a person’s body temperature of 37 ° C) and easy mixing, dissolution is significantly improved water-insoluble drugs in the gastrointestinal tract due to an increase in the specific surface area of small droplets of oil, resulting in a significant increase in the bioavailability of drugs. In addition, emulsions obtained in this way are able to reduce gastrointestinal irritation caused by drugs. Self-emulsifying drugs are able to overcome the disadvantages of traditional drugs, such as instability, low bioavailability, laborious production procedures, large doses, etc.

The self-emulsifying preparation proposed in the present invention has the following weight content of components: Chenopodium ambrosioides L. extract - 1-95%, rapeseed oil - 4-39%, surfactant - 1-45% and secondary surfactant - 0-15 %; preferably, the weight content of the components is: Chenopodium ambrosioides L. extract 20–70%, rapeseed oil 10–30%, surfactant 15–40% and secondary surfactant 5–10%.

In addition, the self-emulsifying preparation of the present invention may also include oil from Adina pilulifera (Lam.) Franch. The preparation has the following weight content of components: Chenopodium ambrosioides L. extract and Adina pilulifera (Lam.) Franch oil. - 1-95%, rapeseed oil - 4-39%, surfactant - 1-45% and secondary surfactant - 0-15%; preferably has the following weight content of the components: Chenopodium ambrosioides L. extract and Adina pilulifera (Lam.) Franch oil. - 20-70%, rapeseed oil - 10-30%, surfactant - 15-40% and secondary surfactant - 5-10%. The weight ratio of the extract of Chenopodium ambrosioides L. and oil from Adina pilulifera (Lam.) Franch. is (1 ~ 5): 1, preferably 3: 1,

Said surfactant is selected from the group consisting of a condensate of polyoxyethylene and castor oil, a condensate of polyoxyethylene and hydrogenated castor oil, polysorbate, phospholipids, etc. or a mixture thereof.

The said condensate of polyoxyethylene and castor oil is a condensate having a different number of polyoxyethylene bonds per molecule, for example polyoxyethylene (35) and castor oil, polyoxyethylene (60) and castor oil, etc. The said condensate of polyoxyethylene and hydrogenated castor oil is a condensate having a different number of polyoxyethylene bonds per molecule, for example polyoxyethylene (35) and hydrogenated castor oil, polyoxyethylene (60) and hydrogenated castor oil, etc. A preferred polysorbate is selected without limitation from polysorbate 60 and polysorbate 80. Said phospholipids include natural and synthesized phospholipids. Mentioned natural phospholipids include egg yolk lecithin and soya lecithin. Said synthesized phospholipids include, but are not limited to, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dimyristoylphosphatidylcholine, etc.

Said secondary surfactant is selected from the group consisting of ethanol, glycol, propanediol, n-butanol, isopropanol, polyglycol 4000 and polyglycol 6000.

The present invention also provides a method for preparing medicinal compositions containing extracts of Chenopodium ambrosioides L., comprising the following steps, in which:

but. extracts of Chenopodium ambrosioides L. are obtained by conventional extraction;

b. in the usual way, pharmaceutically acceptable adjuvants are added to the extracts to obtain the desired formulations.

Chenopodium ambrosioides L. extract can be obtained by conventional methods for extracting essential oils, such as steam distillation, impregnation with an organic solvent (irrigation with an organic solvent), simultaneous distillation-extraction (SDE), supercritical extraction of carbon dioxide, cold pressing, etc. preferably by steam distillation and supercritical extraction of carbon dioxide, and most preferably by steam distillation.

The following optimal steam distillation process is used: the seeds or whole ground parts of Chenopodium ambrosioides L. are added to the distiller, steam is supplied to the collector, the extraction temperature is maintained at 85-100 ° C, distillation is carried out for a certain time, for example 40 minutes, and the essential oil is extracted from Chenopodium ambrosioides L.

Oil from Adina pilulifera (Lam.) Franch. can be obtained by conventional methods of extraction of essential oils, such as steam distillation, impregnation with an organic solvent (irrigation with an organic solvent), simultaneous distillation-extraction (SDE), supercritical extraction of carbon dioxide, cold pressing, etc., preferably by steam distillation and supercritical carbon dioxide extraction, and most preferably by steam distillation. The following optimal process is carried out: the stalks and leaves of Adina pilulifera (Lam.) Franch. Are added to the distiller, steam is supplied to the collector, the extraction temperature is maintained at 85-100 ° C, distillation is carried out for a certain time, for example 40 minutes, and the essential oil is extracted.

Alternatively, Chenopodium ambrosioides L. and Adina pilulifera (Lam.) Franch. can be mixed and extracted using conventional methods for extracting essential oils, such as steam distillation, impregnation with an organic solvent (irrigation with an organic solvent), simultaneous distillation-extraction (SDE), supercritical extraction of carbon dioxide, cold pressing, etc., preferably by steam distillation and supercritical extraction of carbon dioxide, more preferably by steam distillation. The following optimal extraction process is carried out: seeds or whole ground parts of Chenopodium ambrosioides L. and stems and leaves of Adina pilulifera (Lam.) Franch. Are added to the distiller, steam is supplied to the collector, the extraction temperature is maintained at 85-100 ° С, distillation is carried out for a certain time, for example 40 minutes, and the essential oil is recovered.

The method for preparing the gelatin pills compositions of the present invention includes the steps of: dissolving the pharmaceutical gelatin and emollient in distilled water and filtering to obtain a gelatin solution; solvate and dilute the essential oil from Chenopodium ambrosioides L. with vegetable oil in order to obtain a crude oil; add the crude oil and gelatin solution to the gelatin pill manufacturing device, and gelatin tablets with an oily liquid are obtained as contents.

Said emollient is selected from the group consisting of glycerin, xylitol, sorbitol and hydrogenated corn extract.

A method for preparing the self-emulsifying formulations of the present invention includes the steps of: mixing a fixed dose of essential oil from Chenopodium ambrosioides L. or essential oil from Chenopodium ambrosioides L. and oil from Adina pilulifera (Lam.) Franch., Rapeseed oils, surfactants or an additional secondary surfactant, heat the mixture in a water bath at a temperature of 30-80 ° C or using an ultrasonic unit and get a homogeneous and transparent solution, from which m form preparations in the form of soft or hard capsules.

Surfactants used in the aforementioned method for producing said self-emulsifying preparations of the compositions can be selected from a condensate of polyoxyethylene and castor oil, a condensate of polyoxyethylene and hydrogenated castor oil, polysorbate and phospholipid.

In addition, said condensate of polyoxyethylene and castor oil is selected from polyoxyethylene (35) and castor oil, polyoxyethylene (60) and castor oil; said condensate of polyoxyethylene and hydrogenated castor oil is selected from polyoxyethylene (35) and hydrogenated castor oil and polyoxyethylene (60) and hydrogenated castor oil; said polysorbate is selected from polysorbate 60 and polysorbate 80; said phospholipids are selected from egg yolk lecithin, soya lecithin, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine and dimyristoylphosphatidylcholine. Said secondary surfactant is selected from ethanol, glycol, propanediol, n-butanol, isopropanol, polyglycol 4000 and polyglycol 6000.

Chenopodium ambrosioides L. extract and a medicinal composition comprising the extracts mentioned in the present invention can be used for the treatment of gastric diseases caused by HP, such as gastritis, peptic ulcer, etc.

The present invention provides an active ingredient extracted from a medicinal plant of Chinese medicine Chenopodium ambrosioides L. for the treatment of gastric diseases such as gastritis, peptic ulcer, etc., provoked by HP, while its starting material is readily available, the preparation methods are simple and feasible and quality control uncomplicated. In addition, the active ingredient has a pronounced effect, minor side effects and is easily applicable. The self-emulsifying preparations obtained then are directed drugs and are more easily absorbed, thereby increasing the bioavailability of drugs. In addition, the drug is able to weaken the negative reaction of patients, and the stability of drugs is increased by preventing the influence of unstable factors on the drug, such as water, oxygen, etc.

Description of drawings

Figure 1 shows the spectrum of the total ion current of essential oil from Chenopodium ambrosioides L. from Fujian, China,

figure 2 - spectrum of the total ion current of essential oil from Chenopodium ambrosioides L. from Hunan, China,

figure 3 is a spectrum of the total ion current of essential oil from Chenopodium ambrosioides L. from Shaanxi province, China,

figure 4 is a mass chromatogram of α-terpinene,

figure 5 is a mass chromatogram of r-cimol,

figure 6 is a mass chromatogram of α-terpinolene,

Fig.7 is a mass chromatogram of ascaridol.

For the purpose of further clarifying the present invention, but not limiting it in any way, the following experimental examples are given below.

Experimental Example 1

Analysis of the essential oil from Chenopodium ambrosioides L. by gas chromatography-mass spectrometry

1. Extraction of essential oil from Chenopodium ambrosioides L.

1.1. Medicinal materials

Medicinal materials are freshly picked Chenopodium ambrosioide L. plants from Fujian province, China, classified by Tasly Pharmaceutical Co., Ltd. Tianjin Quality Control Department. as a plant Chenopodiaceae, Chenopodium, Chenopodium ambrosio des L. Chenopodium ambrosioides L. plants from Hunan and Shaanxi provinces were supplied by Tasly Pharmaceutical Co., Ltd. in Hunan and Shaanxi.

1.2. Extraction method

300 g of fresh whole ground parts of Chenopodium ambrosioides L. were finely chopped and steam distilled at normal pressure. The distillate was collected until drops of oil were completely distilled off. The fat phase in the upper layer was separated and dried with anhydrous sodium sulfate to give about 2.2 ml of a pale yellow essential oil with a special smell. The oil yield was about 0.75%.

2. Installation and reagents

2.1. Installation

An HP6890 / HP5973 gas chromatograph / mass spectrograph manufactured by Agilent Co., Ltd., USA, was used.

2.2. Reagents

Ethyl acetate (pure for analysis, Tianjin Reagent Plant No. 2); anhydrous sodium sulfate (pure for analysis, Tianjin Plant No. 2 for the production of reagents); deionized water (supplied by the water station of the Tianjin company Tasly Pharmaceutical Co., Ltd.).

3. Chromatography conditions

3.1. Gas Chromatography Conditions

Chromatographic column: HP-5MS flexible silicate capillary column, 60 m × 0.25 mm × 0.25 μm, containing 5% phenylmethylsiloxane;

Thermal programming: the temperature is brought to 80 ° C and maintained at 80 ° C for 10 min, and then increased to 100 ° C at a speed of 4 ° C / min and maintained at this level for 5 min, increased to 150 ° C 5 ° C / min and maintained at this level for 5 minutes, adjusted to 300 ° C at a speed of 20 ° C / min and maintained at this level for 2.5 minutes

Evaporation temperature: 250 ° С;

Carrier gas: high purity helium (99.999%);

Carrier gas mass flow: 1.0 ml / min;

Injected sample volume: 1 μl (ethyl acetate solution);

Dilution Index: 30: 1.

3.2. Mass spectrum conditions

Ion source: EI;

The temperature of the ion source: 230 ° C;

The temperature of the quadrupole rods: 150 ° C;

Electron energy: 70 eV;

Emission Current: 34.6 μA;

Multiplier Voltage: 1781 V;

Contact interaction surface temperature: 280 ° С;

Mass scan range: 10-550 atomic mass units.

4. Procedures

4.1. Qualitative Analysis

1 μl of ethyl acetate solution of essential oil from Chenopodium ambrosioides L. was injected and analyzed by gas chromatography-mass spectrometry, as a result of which 70 chromatographic peaks were detected during full ion chromatography (TIC), as a result of which 33 components were identified by searching in the standard database Nist98 mass spectrometry data from the HP MSD Chemical Station and access to a number of relevant sources.

4.2. The content of each component in essential oil

Using the data processing system of the HP MSD chemical station, the relative percentage of each component was calculated by normalizing the peak area.

5. Results

Figure 1-3 illustrates the full ion chromatography (TIC) of essential oil from Fujian, Hunan and Shaanxi Province, carried out in accordance with the mentioned experimental conditions and procedures, and table 1 shows the results obtained with respect to common components.

Table 1. The results of the detection of components in the essential oil of Chenopodium ambrosioides L.

Connections Molecular formula Cas Chemical structure Relative Content% one 2-pinene C ₁₀ H ₁₆ 80-56-8

0.063% 2 Pinen C ₁₀ H ₁₆ 127-91-3

0,043% 3 Mirzen C ₁₀ H ₁₆ 123-35-3

0.064% four 3-karen C ₁₀ H ₁₆ 13466-78-9

0.080% 5 α-terpene C ₁₀ H ₁₆ 99-86-5

24.418% 6 p-cymol C ₁₀ H ₁₄ 99-87-6

20.142% 7 (+) - (R) -Limonen C ₁₀ H ₁₆ 5989-27-5

0.677% 8 γ-terpene C ₁₀ H ₁₆ 99-85-4

0.595% 9 p-isopropenyltoluene C ₁₀ H ₁₂ 1195-32-0

0.188% 10 3,4-dimethylphenol, 6-ethyl C ₁₀ H ₁₄ O 2219-78-5

0.059% eleven Tsimol C ₁₀ H ₁₄ 25155-15-1

0.077% 12 2-cyclohexen-1-ol, 1-methyl-4- (1-methyl-vinyl) -, trans C ₁₀ H ₁₆ O 7212-40-0

0.086% 13 Cyclooctanone C ₈ H ₁₄ O 502-49-8

0.542% fourteen 1,3,8-p-mentatriene C ₁₀ H ₁₄ 21195-59-5

0,091% fifteen Tsimol C ₁₀ H ₁₄ 25155-15-1

0.128% 16 Durol C ₁₀ H ₁₄ 95-93-2

0,043% 17 Cyclopentane, 1-methyl-2-acetyl-3- (1-methylvinyl) - C ₁₁ H ₁₈ O 55757

0.038% eighteen Transcarveol C ₁₀ H ₁₆ O 1197-07-5

0.138% 19 8-oxabicyclo [5.1.0] oct-5-en-2-ol, 1,4,4-trimethyl- C ₁₀ H ₁₆ O ₂ 58795-43-0

0.173% twenty Terpinolen C ₁₀ H ₁₆ 586-62-9

32,483% 21 7-oxabicyclo [4.1.0] heptan-2-one, 3-methyl-6- (1-methyl ethyl) - C ₁₀ H ₁₆ O ₂ 5729-99-7

0.407% 22 p-mentan-3-one, 1,2-epoxy C ₁₀ H ₁₆ O ₂ 5286-38-4

0.580% 23 m-thymol C ₁₀ H ₁₄ O 89-83-8

0.287% 24 Ascaridol C ₁₀ H ₁₆ O ₂ 512-85-6

14.787% 25 Perylaldehyde C ₁₀ H ₁₄ O 2111-75-3

0.076% 26 3-karen-10-al C ₁₀ H ₁₄ O 151860

0.072% 27 Karyofillen C ₁₅ H ₂₄ 87-44-5

0.155% 28 Isobutyl Tiglate C ₉ H ₁₆ O ₂ 61692-84-0

0.057% 29th Precocene I C ₁₂ H ₁₄ O ₂ 17598-02-6

0.177% thirty β-cubebene C ₁₅ H ₂₄ 13744-15-5

0.041% 31 m-ment-3 (8) -en C ₁₀ H ₁₈ 13828-34-7

0.067% 32 5-nonanol, 2,8-dimethyl- C ₁₁ H ₂₄ O 19780-96-2

0.074% 33 Precocene II C ₁₃ H ₁₆ O ₃ 644-06-4

0.210%

Experimental Example 2

The pharmacodynamic test of the essential oil from Chenopodium ambrosioides L.

Experimental materials

1. Tested medicine

Essential oil from Chenopodium ambrosioides L .: yellow oily substance obtained by the method according to Example 5 (batch number: 20040129), supplied by Tianjin company Tasly Pharmaceutical Co., Ltd., stored in a sealed volumetric flask and diluted with vegetable oil to the desired concentration until use for introducing (for example) animals.

2. Medication for positive control

Ranitidine (batch number: 030836): purchased from Shijiazhuang No. 4 Pharmaceutical Co., Ltd.

3. Reagents

3.1. Vegetable oil: marketed natural mixed fusel oil, batch number: 03110405.

3.2. Acetic acid: Acquired from Tianjin Tianhe Reagent Plant, batch number: 20030722.

3.3. 2% Chinese mascara: purchased from Beijing Xizhong Chemical Plant, batch number: 980301 and diluted with 5% gum arabic solution.

3.4. HP strain: strain according to international standard 26695.

3.5. Culture medium: Columbia agar culture obtained from Oxoid, UK.

3.6. Antibiotics: vancomycin hydrochloride, apolymyxin B, amphotericin B manufactured by Sigma.

3.7. Gas mixture (5% O ₂ , 10% CO ₂ , 85% N ₂ ): Beijing company Pulaikesi Practical Gas Co., Ltd.

4. Experimental animals

4.1. Km mice weighing 18-22 g, equally males and females.

4.2. Uistar rats weighing 160-220 g, equally males and females. Experimental animals were provided by the Tianjin Pharmaceutical Research Institute Veterinary Laboratory (certificate number: W-J Tianjin Experimental Animal Quality R Authorized No. 001).

All animals were monitored under conditions with central air conditioning (according to the standard for the ultimate level, Tianjin Experimental Facility Authorized No. 012). Mice and rats were given tap water and a special complete balanced diet purchased from Tianjin Huarong Experimental Animal Technology Co., Ltd.

Methods and Results

1. The effect on gastric ulcer in rats, provoked by cauterization with acetic acid

For this experiment, eighty Wistar rats weighing 200-220 g were selected, equally males and females, which were randomly divided into 8 groups of 10 rats per group. Rats were once daily injected with drugs once a day for 13 days, for example, in the dosage shown in Table 2, and for rats from the model control group, for example, the same amount of vegetable oil was administered. The model was created 2 hours after the third injection. Rats were not fed for 24 hours before the creation of the model, after which they were euthanized with ether, their abdomen was shaved and disinfected. A small incision was made along the xiphoid midline. The stomach was carefully removed, 10 μl of 40% acetic acid was injected under the outer membrane of the stomach near the areas of the pyloric glands. Then the stomach was placed back into the abdominal cavity and the incision was sutured. After surgery, drugs were administered. Rats were not fed for 24 hours after the last administration of the drug, after which the animals were killed, after having been euthanized with uratan. The abdominal cavity was opened, the entire stomach was removed and it was opened along the greater curvature of the stomach. The contents of the stomach were washed with saline, after which the stomach was placed in 1% formaldehyde for 10 minutes, and then the diameters of ulcerations were measured using precise measuring forks and the area of ulcers was calculated. Mascara was injected using a microsyringe until its level reached the surface of the gastric mucosa, after which the volume of the introduced carcass was recorded. The degree of ulcer was expressed in terms of the area of ulceration and the volume of injected carcass. According to the results (see table 2), the area of the ulcer, as well as the volume of the injected carcass, decreased in the groups that were injected with a sample of essential oil from Chenopodium ambrosioides L., which indicates that the drug has a significant effect on accelerating healing of the ulcer.

table 2

±SD, n=10)The action of the essential oil from Chenopodium ambrosioides L. on a stomach ulcer provoked by cauterization with acetic acid (

± SD, n = 10) Groups Dosage (mg / kg) The area of the ulcer (mm ² ) The volume of the carcass introduced into the area of the ulcer (μl) Model control group - 24.52 ± 11.29 7.74 ± 3.83 Ranitidine 200 8.08 ± 5.72 ** 2.85 ± 2.63 ** High dosage twenty 10.57 ± 5.45 ** 3.25 ± 1.24 ** Essential oil from Chenopodium ambrosioides L. Moderate dosage 10 8.93 ± 6.64 ** 2.27 ± 1.84 ** Low dosage 5 8.71 ± 5.41 ** 1.67 ± 1.29 *** Compared with the model control group * p <0.05, ** p <0.01, *** p <0.001.

2. Effect on gastric ulcer caused by ligation of pylorus in rats

For this experiment, eighty Wistar rats weighing 160 g were selected, equally males and females, which were randomly divided into 8 groups of 10 rats per group. Rats were injected with drugs once a day for 3 days, for example, in the dosage shown in Table 3, and for rats from the model control group, for example, the same amount of vegetable oil was administered. The animals were euthanized 2 hours after the last injection (rats were not fed for 48 hours before administration), their abdomen was shaved and disinfected. A small incision was made below the xiphoid midline. The stomach was carefully removed, and then again placed in the abdominal cavity after ligation of the pylorus, after which the incision was sutured. After the operation, the rats were not allowed to eat or drink for 6 hours and then killed, after having been euthanized. The abdominal cavity was opened, the cardiac section of the stomach was bandaged, the entire stomach was removed and it was opened along the greater curvature of the stomach. The contents of the stomach were washed with saline, after which the stomach was placed in 1% formaldehyde for 10 minutes, and then the diameters of ulcerations were measured using precise measuring forks. The degree of ulcer was expressed in terms of the total area of ulceration in each rat and was assigned to 5 stages according to the Okabe method as an ulcer index. According to the results (see table 3), the ulcer indices in the groups administered the medicine are significantly lower than in the model control group, which indicates that the essential oil from Chenopodium ambrosioides L. can significantly inhibit the development of gastric ulcers caused by ligation of the pylorus.

Table 3

, n=10)The action of the essential oil from Chenopodium ambrosioides L. on a stomach ulcer caused by ligation of the pylorus (

, n = 10) Groups Dosage (mg / kg) Ulcer index Model control group - 2.7 ± 1.8 Ranitidine High of dosage 200 0.8 ± 0.6 ** Essential oil from Chenopodium ambrosioides L. Moderate dosage twenty 0.9 ± 0.6 * Low dosage 10 1.0 ± 0.8 * 5 0.9 ± 0.6 * Compared to the model control group * p <0.05, ** p <0.01,

Note: Ulcer Index Rating Standard

Ulcer index one 2 3 four 5 The area of the ulcer (mm ² ) 1-12 13-25 26-37 38-50 ≥50 or perforation of the stomach

In the case of ulcerations with an area of less than 1 mm ^{2, the} total area of ten such ulcerations is 1 mm ² .

3. Effect on the propulsive movement of food in the intestines in mice

For the experiment, eighty Km mice weighing 18-22 g were selected, equally males and females, which were randomly divided into groups of 10 mice per group. Once a day for 3 days, the mice were constantly injected with drugs, for example, in the dosage shown in table 4, and the mice from the control group were injected, for example, with the same amount of vegetable oil. Animals in each group were injected, for example, 2% of Chinese carcass (in the form of a solution in 5% gum arabic) 40 minutes after the last drug administration (mice were not fed for 24 hours before drug administration), and the same volume was administered to mice from the control group 5% gum arabic solution. After 20 minutes, the mice were killed by displacing the cervical vertebra. The abdominal cavity was opened and carefully removed the entire stomach and intestines, divided and laid out on waxed cardboard. To determine the length of the intestine, the distance from the pylorus to the ileocecal region was measured. Measured the distance from the pylorus to the border of the carcass advancement to determine the range of propulsive food advancement in the intestine. The ratio between the range of propulsive advancement of food in the intestine and the total length of the intestine was used to calculate the degree of propulsive advancement. The average values of the degree of propulsive advancement in each group receiving the drug and in the control group were tested according to criterion T. As the results show (see table 4), the degree of propulsive advancement of essential oil from Chenopodium ambrosioides L. in the intestine at a high and moderate dosage is noticeable lower than in the control group, which indicates that the drug significantly inhibits the function of propulsive food promotion in the intestine.

Table 4

, n=10)The action of the essential oil from Chenopodium ambrosioides L. propulsive promotion of food in the intestines in mice (

, n = 10) Groups Dosage (mg / kg) Extent of propulsive carcass advancement

Control group - 49.25 ± 5.82 Atropine group fifteen 25.51 ± 10.92 *** Essential oil from Chenopodium ambrosioides L. High dosage twenty 32.73 ± 16.41 * Moderate dosage 10 31.30 ± 20.11 * Low dosage 5 30.47 ± 27.04 Compared with the control group * p <0.05, *** p <0.001.

4. In vitro Inhibitory Test on Helicobacter Pylori

Bacterial strain: a bacterial strain according to international standard 26695.

Preparation of culture medium: in 3.9 g of culture on Columbia agar, under pressure of 15 pounds, 100 ml of water was added over 20 minutes. After cooling to 50 ° C under sterile conditions, 7 ml of defibrinated sheep blood and 2 ml of antibiotics were added.

The conditions for the cultivation of a gas mixture: a gas mixture of 5% O ₂ , 10% CO ₂ and 85% N ₂ at a constant temperature of 37 ° C.

The medicine was ground together with the egg yolk and an emulsified solution was obtained. After sterilization under high pressure, the emulsified solution was subjected to serial dilution and mixed with a nutrient medium. 100 μl of the prepared bacterial solution was added to each culture dish and carefully dispensed. After cultivation in a medium of weakly anaerobic bacteria at a temperature of 37 ° C for 72 hours, the results were studied. The lowest concentration of essential oil from Chenopodium ambrosioides L. in a culture plate without HP growth was rated as the minimum inhibitory concentration. As the results show (see table 5), the minimum inhibitory concentration of the essential oil from Chenopodium ambrosioides L. was 0.097 mg / ml, which indicates that the drug has a significant inhibitory effect on HP.

Table 5 Inhibitory effect of in vitro essential oil from Chenopodium ambrosioides L. on HP Medicine Drug Concentrations (mg / ml) 24.8 12,4 6.2 3,1 1.55 0.78 0.39 0.194 0,097 0,048 0.024 0.012 0 Essential oil from Chenopodiu mambrosioides L. - - ++ ++ ++ "++" means parallel samples in which HP growth occurs. "-" means parallel samples in which HP growth is not detected.

findings

As the four described experiments show, the essential oil of Chenopodium ambrosioides L. proposed in the present invention has a significant effect accelerating the healing of a stomach ulcer, provoked by cauterization with acetic acid; significant inhibitory effect on gastric ulcer caused by ligation of the pylorus; significant inhibitory effect on the function of propulsive food promotion in the intestine; and a significant inhibitory effect on HP growth in vitro.

Examples

The following examples are provided to illustrate the scope of the present invention, and not to limit it in any way.

It should be noted that the ratios given below in the examples are weight ratios, and all fractions mean weight fractions.

Example 1. Obtaining essential oils from Chenopodium ambrosioides L.

1000 g of the ground parts of the plant Chenopodium ambrosioides L. were weighed and placed in an extractor, the extraction temperature was maintained at 35 ° C at a pressure of 30 MPa. The extraction lasted 5 hours at a consumption of CO _{2 of} 5 l / (kg of drug material · h), as a result of which 5 g of essential oil was obtained by the method of supercritical extraction of CO ₂ .

Example 2. Obtaining essential oils from Chenopodium ambrosioides L.

1000 g of the ground parts of the plant Chenopodium ambrosioides L. were weighed and placed in an extractor, the extraction temperature was maintained at 48 ° C at a pressure of 30 MPa. The extraction lasted 8 hours at a consumption of CO _{2 of} 7 l / (kg of drug material · h), as a result of which 4.6 g of essential oil was obtained by the method of supercritical extraction of CO ₂ .

Example 3. Obtaining essential oils from Chenopodium ambrosioides L.

1000 g of the ground parts of the Chenopodium ambrosioides L. plant were placed in a distiller, steam was fed into the collector, and the extraction temperature was maintained at 85 ° C. After distillation for 40 minutes, 4.8 g of essential oil was collected.

Example 4. Obtaining essential oils from Chenopodium ambrosioides L.

1000 g of the ground parts of the Chenopodium ambrosioides L. plant were placed in a distiller, steam was fed into the collector, and the extraction temperature was maintained at 95 ° C. After distillation for 40 minutes, 5.2 g of essential oil was collected.

Example 5. Obtaining essential oils from Chenopodium ambrosioides L.

1000 g of the ground parts of the Chenopodium ambrosioides L. plant were placed in a distiller, steam was fed into the collector, and the extraction temperature was maintained at 90 ° С. After distillation for 40 minutes, 4.5 g of essential oil was collected.

Example 6. Obtaining oil from Adina pilulifera (Lam.) Franch.

1000 g of stems and leaves of Adina pilulifera (Lam.) Franch. placed in a distiller, steam was fed into the collector and the extraction temperature was maintained at 95 ° C. After distillation for 40 minutes, 5.5 g of essential oil was obtained.

Example 7. Obtaining oil from Adina pilulifera (Lam.) Franch.

1000 g of stems and leaves of Adina pilulifera (Lam.) Franch. placed in an extractor and the extraction temperature was maintained at 35 ° C at a pressure of 30 MPa. The extraction lasted 4 hours at a consumption of CO _{2 of} 5 l / (kg of drug material · h), as a result of which 5.5 g of essential oil was obtained by the method of supercritical extraction of CO ₂ .

Example 8. Obtaining essential oils from Chenopodium ambrosioides L. and oils from Adina pilulifera (Lam.) Franch.

600 g of whole Chenopodium ambrosioides L. plants along with 400 g of the stems and leaves of Adina pilulifera (Lam.) Franch. placed in the extractor, the extraction temperature was maintained at 35 ° C at a pressure of 30 MPa. The extraction lasted 5 hours at a consumption of CO _{2 of} 5 l / (kg of drug material · h), as a result of which 10.3 g of essential oil were obtained by the method of supercritical extraction of CO ₂ .

Example 9. Obtaining essential oils from Chenopodium ambrosioides L. and oils from Adina pilulifera (Lam.) Franch.

500 g of whole Chenopodium ambrosioides L. plants, together with 500 g of stems and distillation for 40 min, 9.8 g of essential oil was obtained.

Example 10. Obtaining gelatin pills

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 60 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the Chenopodium ambrosioides L. essential oil obtained according to Example 1, and the weight ratio of the Chenopodium ambrosioides L. vegetable oil and essential oil was 3: 1, mixed well and a crude oil was obtained.

The gelatin solution obtained above, together with the crude oil, was placed in an automatic rotary capsule machine and placed in gelatin pills at the rate of 100 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 11. Obtaining gelatin pills

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the Chenopodium ambrosioides L. essential oil obtained according to Example 2, and the weight ratio of Chenopodium ambrosioides L. vegetable oil and essential oil was 2: 1, mixed well and a crude oil was obtained.

The gelatin solution obtained above, together with the crude oil, was placed in an automatic rotary capsule machine and placed in gelatin pills at the rate of 90 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 12. Obtaining gelatin pills

100 servings of gelatin were added to 130 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 80 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the Chenopodium ambrosioides L. essential oil obtained according to Example 3, and the weight ratio of the Chenopodium ambrosioides L. vegetable oil and essential oil was 1.5: 1, mixed well and a crude oil was obtained.

The gelatin solution obtained above together with the crude oil was placed in a drop molding machine and gelatin pills were obtained at the rate of 90 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 13. Obtaining gelatin pills

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 35 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to the aforementioned glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the essential oil from Chenopodium ambrosioides L., obtained according to Example 5, while the weight ratio of vegetable oil and essential oil from Chenopodium ambrosioides L. was 1: 1, mixed well and the crude oil was obtained.

The gelatin solution obtained above together with the crude oil was placed in a drop molding machine and gelatin pills were obtained at the rate of 80 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 14. Obtaining gelatin pills

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 40 servings of xylitol was heated to 80 ° C, and then the swollen gelatin was added to the mentioned xylitol, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the Chenopodium ambrosioides L. essential oil obtained according to Example 4, and the weight ratio of the Chenopodium ambrosioides L. vegetable oil and essential oil was 1: 1, mixed well and a crude oil was obtained.

The gelatin solution obtained above together with the crude oil was placed in a drop molding machine and gelatin pills were obtained at the rate of 80 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 15. Obtaining gelatin pills

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 60 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the Chenopodium ambrosioides L. essential oil obtained according to Example 5, while the weight ratio of Chenopodium ambrosioides L. essential oil to 1.1: 1 was mixed well, and a crude oil was obtained.

The gelatin solution obtained above together with the crude oil was placed in a drop molding machine and gelatin pills were obtained at the rate of 80 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 16. Obtaining gelatin pills

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of sorbitol was heated to 80 ° C, and then the swollen gelatin was added to the aforementioned sorbitol, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the Chenopodium ambrosioides L. essential oil obtained according to Example 5, and the weight ratio of Chenopodium ambrosioides L. essential oil to 1.3: 1 was well mixed and the crude oil was obtained.

The gelatin solution obtained above together with the crude oil was placed in a soft capsule filling unit and gelatin pills were obtained at the rate of 80 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 17. Obtaining gelatin pills

100 servings of gelatin were added to 110 servings of water, the mixture was allowed to swell by absorption of water. An additional 40 servings of hydrogenated corn extract was heated to 80 ° C, and then the swollen gelatin was added to said hydrogenated corn extract, mixed, melted and a gelatin solution was obtained which was kept warm for use.

Vegetable oil was added to the Chenopodium ambrosioides L. essential oil obtained according to Example 5, and the weight ratio of the Chenopodium ambrosioides.L essential oil and oil was 2.5: 1, mixed well and a crude oil was obtained.

The gelatin solution obtained above, together with the crude oil, was placed in a rotary tablet capsule capsule machine and gelatin pills were obtained at the rate of 90 mg of an oily liquid per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 18. Obtaining gelatin pills

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the essential oil from Chenopodium ambrosioides L. obtained according to Example 2, while the weight ratio of vegetable oil to the essential oil from Chenopodium ambrosioides L. was 1: 1; subjected to cutting to achieve the appropriate dispersion using the installation for cutting, dispersion, emulsification and received the crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in a rotary capsule capsule machine and gelatin pills were obtained at the rate of 120 mg of an oily liquid per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 19. Obtaining gelatin pills

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of sorbitol was heated to 60 ° C, and then the swollen gelatin was added to the said sorbitol, mixed, melted and a gelatin solution was obtained, which was stored in heat for use.

Vegetable oil was added to the essential oil from Chenopodium ambrosioides L., obtained according to Example 5, while the weight ratio of vegetable oil and essential oil from Chenopodium ambrosioides L. was 2: 1; subjected to cutting to achieve the appropriate dispersion using the installation for cutting, dispersion, emulsification and received the crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in a drop molding machine to obtain gelatin pills based on 150 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 20. Obtaining gelatin pills

100 servings of gelatin were added to 130 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

Vegetable oil was added to the essential oil from Chenopodium ambrosioides L. obtained according to Example 4, while the weight ratio of vegetable oil to the essential oil from Chenopodium ambrosioides L. was 2.5: 1; subjected to cutting to achieve the appropriate dispersion using the installation for cutting, dispersion, emulsification and received the crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in a drop molding machine, and gelatin pills were obtained at the rate of 140 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, gelatin pills were obtained.

Example 21. Obtaining tablets

56 g of the essential oil from Chenopodium ambrosioides L. obtained according to Example 1 was mixed with starch in a ratio of 1: 1, 25 g of sodium carboxymethyl cellulose was added to the resulting mixture and mixed well. A 75% ethanol solution was added as a binder, sieved through a No. 22 sieve, and dried in an oven at a temperature of 40 ° C. An appropriate amount of magnesium stearate was added, tableted, and 300 mg tablets were each obtained.

Example 22. Obtaining coated tablets

53 g of the essential oil from Chenopodium ambrosioides L. obtained according to Example 4 was mixed with 17 g of basic magnesium oxide and 17 g of starch and 17 g of lactose were added. A 0.5% aqueous HPMC solution was used as a binder, and simple tablets were obtained with 300 mg per tablet. The tablets were coated with 30% Eudragit RL30D and tablets were coated with a content of 300 mg per tablet.

Example 23. Obtaining capsules

52 g of the essential oil from Chenopodium ambrosioides L., obtained according to Example 3, was mixed with starch in a ratio of 1: 1, 25 g of sodium carboxymethyl cellulose was added to the resulting mixture and mixed well. A 75% ethanol solution was added as a binder, sieved through a No. 22 sieve, dried in an oven at 40 ° C, granulated, placed in hard capsules and capsules containing 270 mg per capsule were obtained.

Example 24. Obtaining a concentrated pill

53 g of the essential oil from Chenopodium ambrosioides L. obtained according to Example 5 was mixed with microcrystalline cellulose, while the amount of microcrystalline cellulose was 40% of the essential oil from Chenopodium ambrosioides L., water was added as a binder, and a simple pill was obtained.

The aforementioned simple pill was coated with Opatry (soluble in the stomach) coating material manufactured by Shanghai Colorcon Coating Technology Co., Ltd. and got a concentrated pill.

The coating was carried out under the following conditions: water was used as a solvent; the concentration of the solution for coating was 20%; coating weight increased by 5%; the inlet air temperature was 80 ° C; the temperature of the table on the coating was 45 ° C; spray pressure was 2.0 bar; the rotation speed of the bath with coating solution was 17 rpm; the flow rate of the feed was 3 g / min.

Example 25. Obtaining granules

53 g of essential oil from Chenopodium ambrosioides L. obtained according to Example 5, 9 g of methyl cellulose and 820 g of powdered sugar were mixed well; an appropriate amount of 70% ethanol was added. Soft material was formed from the mixture, granulated, and ethanol evaporated; spray dried at a temperature of 80 ° C and obtained granules.

Example 26. Obtaining drip pills

300 g of polyglycol 6000 was heated to a temperature of 80 ° C and after melting the polyglycol 50 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 3, was added, mixed well and placed in a drop molding machine. The temperature of the molten solution was maintained at 70 ° C, the solution was introduced dropwise at a moderate speed into methyl silicone oil at a temperature of 10 ° C and droplet pills were obtained.

Example 27. Obtaining drip pills

300 g of polyglycol 4000 was heated to a temperature of 75 ° C and after melting the polyglycol, 53 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 5, was added, mixed well and placed in a drop molding machine. The temperature of the molten solution was maintained at 65 ° C, the solution was introduced dropwise at a moderate speed into liquid paraffin at a temperature of 0 ° C and droplet pills were obtained.

Example 28. Obtaining drip pills

300 g of polyglycol 4000 was heated to a temperature of 90 ° C and after melting of the polyglycol 60 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 1, was added, mixed well and placed in a drop molding machine. The temperature of the molten solution was maintained at 80 ° C, the solution was introduced dropwise at a moderate speed into liquid paraffin at a temperature of 4 ° C and droplet pills were obtained.

Example 29. Obtaining oral fluid

500 g of the essential oil from Chenopodium ambrosioides L. obtained according to Example 5 was dissolved in an appropriate amount of ethanol, 10 g of glyceryl monostearate and 50 g of sucrose were added and mixed well, then distilled water was added to 1000 ml, filtered, disinfected, packaged and the finished product was obtained .

Example 30. Obtaining self-emulsifying soft capsules from the extract of Chenopodium ambrosioides L.

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 60 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

10 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 1, 390 g of rapeseed oil, 500 g of polyoxyethylene (35) and castor oil and 100 g of glycol were heated in a water bath at a temperature of 30 ° C in order to obtain a uniform and clear solution, as a result, they received an untreated medicine.

The gelatin solution obtained above together with the crude oil was placed in an encapsulation machine and soft capsules were obtained at the rate of 100 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 31. Obtaining self-emulsifying soft capsules from the extract of Chenopodium ambrosioides L.

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to said glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

200 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 1, 350 g of rapeseed oil, 250 g of polyoxyethylene (60) and castor oil and 200 g of soya lecithin were mixed using an ultrasonic device to obtain a uniform and clear solution with a temperature of 50 ° C, resulting in crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in an encapsulation machine and soft capsules were obtained at the rate of 100 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 32. Obtaining self-emulsifying soft capsules from the extract of Chenopodium ambrosioides L.

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of sorbitol was heated to 60 ° C, and then the swollen gelatin was added to the said sorbitol, mixed, melted and a gelatin solution was obtained, which was stored in heat for use.

275 g of essential oil from Chenopodium ambrosioides L. obtained according to Example 2, 325 g of rapeseed oil, 300 g of polyoxyethylene (60) and castor oil, 50 g of egg yolk lecithin and 50 g of propanediol were heated in a water bath at a temperature of 60 ° C with the aim of obtaining a homogeneous and transparent solution, resulting in a crude drug,

The gelatin solution obtained above, together with the crude oil, was placed in an encapsulation machine and soft capsules were obtained at the rate of 150 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 33. Obtaining self-emulsifying soft capsules from the extract of Chenopodium ambrosioides L.

100 servings of gelatin were added to 130 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of sorbitol was heated to 80 ° C, and then the swollen gelatin was added to the aforementioned sorbitol, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

600 g of essential oil from Chenopodium ambrosioides L. obtained according to Example 3, 100 g of rapeseed oil, 50 g of polyoxyethylene (35) and hydrogenated castor oil, 20 g of polysorbate 80, 80 g of distearoylphosphatidylcholine, 30 g of dimyristoylphosphatidylcholine and 120 g of polyglycol 4000 using an ultrasonic installation in order to obtain a uniform and transparent solution with a temperature of 80 ° C, resulting in a crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in an encapsulation machine and soft capsules were obtained at the rate of 120 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 34. Obtaining self-emulsifying soft capsules from the extract of Chenopodium ambrosioides L.

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 35 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to the aforementioned glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

735 g of essential oil from Chenopodium ambrosioides L. obtained according to Example 3, 65 g of rapeseed oil, 50 g of polysorbate 60, 150 g of polyoxyethylene (60) and hydrogenated castor oil were mixed using an ultrasonic device to obtain a uniform and clear solution with a temperature of 70 ° C, resulting in a crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in an encapsulation machine and soft capsules were obtained based on 150 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 35. Obtaining self-emulsifying hard capsules from the extract of Chenopodium ambrosioides L.

950 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 2, 50 g of rapeseed oil and 20 g of polyoxyethylene (35) and hydrogenated castor oil were mixed using an ultrasonic device in order to obtain a uniform and clear solution with a temperature of 70 ° C, then a solution hard shell capsules were filled and capsules were obtained at a rate of 270 mg of contents per capsule.

Example 36. Obtaining self-emulsifying hard capsules from the extract of Chenopodium ambrosioides L.

950 g of the essential oil from Chenopodium ambrosioides L. obtained according to Example 2, 40 g of rapeseed oil, 30 g of polyoxyethylene (60), hydrogenated castor oil and 80 g of isopropanol were mixed using an ultrasonic device to obtain a uniform and clear solution with a temperature of 30 ° C, then the capsule with the hard shell was filled with the solution and capsules were obtained at the rate of 300 mg of contents per capsule.

Example 37. Obtaining self-emulsifying hard capsules from the extract of Chenopodium ambrosioides L.

960 g of essential oil from Chenopodium ambrosioides L. obtained according to Example 1, 40 g of rapeseed oil and 15 g of polyoxyethylene (35) and hydrogenated castor oil were mixed using an ultrasonic device to obtain a uniform and clear solution with a temperature of 70 ° C, then a solution hard shell capsules were filled and capsules were obtained at a rate of 200 mg of contents per capsule.

Example 38. Obtaining self-emulsifying hard capsules from the extract of Chenopodium ambrosioides L.

335 g of essential oil from Chenopodium ambrosioides L. obtained according to Example 5, 365 g of rapeseed oil, 150 g of polysorbate 80 and 150 g of soya lecithin were heated in a water bath at a temperature of 80 ° C to obtain a uniform and clear solution, then capsules were filled with the solution with a hard shell and capsules were obtained at the rate of 270 mg of contents per capsule.

Example 39. Obtaining self-emulsifying soft capsules from essential oils from Chenopodium ambrosioides L. and oils from Adina pilulifera (Lam.) Franch.

100 servings of gelatin were added to 120 servings of water, the mixture was allowed to swell by absorption of water. An additional 30 servings of sorbitol was heated to 80 ° C, and then the swollen gelatin was added to the aforementioned sorbitol, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

450 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 1, 150 g of oil from Adina pilulifera (Lam.) Franch., Obtained according to Example 6, 100 g of rapeseed oil, 50 g of polyoxyethylene (35) and hydrogenated castor oil, 20 g of polysorbate 80, 80 g of distearoylphosphatidylcholine, 30 g of dimyristoylphosphatidylcholine and 120 g of polyglycol 4000 were mixed using an ultrasonic apparatus to obtain a homogeneous and clear solution with a temperature of 80 ° C, resulting in a crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in an encapsulation machine and soft capsules were obtained at the rate of 120 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 40. Obtaining self-emulsifying soft capsules from essential oils from Chenopodium ambrosioides L. and oils from Adina pilulifera (Lam.) Franch.

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 35 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to the aforementioned glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

335 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 3, 365 g of oil from Adina pilulifera (Lam.) Franch., Obtained according to Example 6, 100 g of rapeseed oil, 10 g of polyoxyethylene (60) and hydrogenated castor oil, 20 g of polysorbate 80, 80 g of distearoylphosphatidylcholine and 120 g of polyglycol 4000 were mixed using an ultrasonic apparatus in order to obtain a homogeneous and transparent solution with a temperature of 60 ° C, resulting in a crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in an encapsulation machine and soft capsules were obtained at the rate of 150 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 41. Obtaining self-emulsifying soft capsules from essential oils from Chenopodium ambrosioides L. and oils from Adina pilulifera (Lam.) Franch.

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 35 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to the aforementioned glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

490 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 2, 245 g of oil from Adina pilulifera (Lam.) Franch., Obtained according to Example 7, 65 g of rapeseed oil, 50 g of polysorbate 60, and 150 g of polyoxyethylene (60) and hydrogenated castor oil was mixed using an ultrasonic apparatus to obtain a homogeneous and clear solution with a temperature of 70 ° C, resulting in a crude oil.

The gelatin solution obtained above, together with the crude oil, was placed in an encapsulation machine and soft capsules were obtained at the rate of 120 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 42. Obtaining self-emulsifying soft capsules from essential oils from Chenopodium ambrosioides L. and oils from Adina pilulifera (Lam.) Franch.

100 servings of gelatin were added to 140 servings of water, the mixture was allowed to swell by absorption of water. An additional 35 servings of glycerin was heated to 70 ° C, and then the swollen gelatin was added to the aforementioned glycerin, mixed, melted and a gelatin solution was obtained, which was kept warm for use.

735 g of essential oil from Chenopodium ambrosioides L. and oil from Adina pilulifera (Lam.) Franch. Obtained according to Example 8, 65 g of rapeseed oil, 50 g of polysorbate 60 and 120 g of polyoxyethylene (60), and hydrogenated castor oil were mixed using ultrasonic installation in order to obtain a homogeneous and transparent solution with a temperature of 70 ° C, resulting in a crude oil.

The gelatin solution obtained above together with the crude oil was placed in an encapsulation machine and soft capsules were obtained at the rate of 100 mg of an oily liquid of contents per capsule. After molding, drying, washing, sterilizing and packaging, soft capsules were obtained.

Example 43. Obtaining self-emulsifying hard capsules from essential oils from Chenopodium ambrosioides L. oils from Adina pilulifera (Lam.) Franch.

800 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 1, 150 g of oil from Adina pilulifera (Lam.) Franch., Obtained according to Example 6, 40 g of rapeseed oil and 10 g of polyoxyethylene (35), and hydrogenated castor oil were mixed using an ultrasonic device in order to obtain a uniform and transparent solution with a temperature of 70 ° C, then the capsule with a hard shell was filled with the solution and capsules were obtained at the rate of 200 mg of contents per capsule.

Example 44. Obtaining self-emulsifying hard capsules from essential oils from Chenopodium ambrosioides L. oils from Adina pilulifera (Lam.) Franch.

450 g of essential oil from Chenopodium ambrosioides L., obtained according to Example 2, 150 g of oil from Adina pilulifera (Lam.) Franch., Obtained according to Example 6, 100 g of rapeseed oil and 10 g of polyoxyethylene (35), and hydrogenated castor oil were mixed using an ultrasonic device in order to obtain a uniform and transparent solution with a temperature of 50 ° C, then the capsule with a hard shell was filled with the solution and capsules were obtained at the rate of 270 mg of contents per capsule.

Example 45. Obtaining self-emulsifying hard capsules of essential oils from Chenopodium ambrosioides L. and oil obtained from Adina pilulifera (Lam.) Franch.

500 g of essential oil from Chenopodium ambrosioides L. and oil from Adina pilulifera (Lam.) Franch. Obtained according to Example 9, 80 g of rapeseed oil and 420 g of polyoxyethylene (60), and hydrogenated castor oil were mixed using an ultrasonic apparatus to obtain homogeneous and transparent solution with a temperature of 50 ° C, then the capsule with a hard shell was filled with the solution and capsules were obtained at the rate of 270 mg of contents per capsule.

Claims (24)

1. An extract of Chenopodium ambrosioides L. having the following weight content of components: α-terpinene 15-35%, p-cymol 15-25%, ascaridol 10-20% and α-terpinolene 32-40%. 2. Chenopodium ambrosioides L. extract according to claim 1, having the following weight content of components: α-terpinene 20-30%, p-cymol 18-22%, ascaridol 12-18% and α-terpinolene 32-35%. 3. Chenopodium ambrosioides L. extract according to claim 2, having the following weight content of the components: α-terpinene 22-25%, p-cymol 19-21%, ascaridol 13-15% and α-terpinolene 32-33%. 4. Chenopodium ambrosioides L. extract according to claim 1, further having the following weight content of the components: γ-terpinene 0.5-0.7% and / or limonene 0.6-0.8%. 5. Chenopodium ambrosioides L. extract according to claim 4, having the following weight content of γ-terpinene and limonene: γ-terpinene 0.5-0.6% and / or limonene 0.6-0.7%. 6. A medicinal composition containing an extract of Chenopodhim ambrosioides L. according to any one of claims 1 to 5 as the only active ingredient and pharmaceutically acceptable adjuvants. 7. The pharmaceutical composition according to claim 6, from which various dosage forms are prepared. 8. The drug composition according to claim 7, the dosage form of which is gelatin pills, consisting of the contents and coating material, while the contents of the gelatin pills is Chenopodium ambrosioides L. extract according to any one of claims 1 to 5 and vegetable oil. 9. The drug composition of claim 8, in which the weight ratio of the extract of Chenopodium ambrosioides L. and vegetable oil is 1: (1-3). 10. The drug composition of claim 8, in which the weight ratio of Chenopodium ambrosioides L. extract and vegetable oil is 1: (1-2). 11. The drug composition of claim 8, in which the weight ratio of the extract of Chenopodium ambrosioides L. and vegetable oil is 1: 1. 12. The drug composition of claim 8, in which the coating material contains gelatin and a softener, wherein the softener is selected from the group consisting of glycerin, xylitol, sorbitol, and hydrogenated corn extract. 13. The pharmaceutical composition according to claim 7, the dosage forms of which are self-emulsifying preparations having the following weight content of components: Chenopodium ambrosioides L. extract according to any one of claims 1-5, 1-95%, rapeseed oil 4-39%, surface-active substance 1-45% and secondary surfactant 0-15%. 14. The pharmaceutical composition according to item 13, having the following weight content of components: Chenopodium ambrosioides L. extract 20-70%, rapeseed oil 10-30%, surfactant 15-40% and secondary surfactant 5-10% . 15. The drug composition according to item 13 or 14, in which the surfactant is selected from the group comprising a condensate of polyoxyethylene and castor oil, a condensate of polyoxyethylene and hydrogenated castor oil, polysorbate and phospholipids, and the secondary surfactant is selected from the group including ethanol, glycol, propanediol, n-butanol, isopropanol, polyglycol 4000 and polyglycol 6000. 16. The drug composition of claim 15, wherein the condensate of polyoxyethylene and castor oil is selected from polyoxyethylene (35) and castor oil and polyoxyethylene (60) and castor oil, the condensate of polyoxyethylene and hydrogenated castor oil is selected from polyoxyethylene (35) hydrogenated castor oil and polyoxyethylene (60) hydrogenated castor oil, polysorbate selected from polysorbate 60 and polysorbate 80, phospholipids selected from the group consisting of egg yolk lecithin, soya lecithin, dipalmitoylphos atidilholin, distearoylphosphatidylcholine and dimyristoyl phosphatidylcholine. 17. The method of obtaining a medicinal composition according to claim 6, which contains an extract of Chenopodium ambrosioides L. according to any one of claims 1 to 5 as the only active ingredient, comprising the following stages, in which:
a. Chenopodium ambrosioides L. extracts are obtained by steam distillation as follows: Chenopodium ambrosioides L. seeds or whole ground parts are added to the distiller, steam is fed to a collector in which Chenopodium ambrosioides L. seeds or whole ground parts are distilled, the extraction temperature is maintained at 85- 100 ° C., distill for 40 minutes and extract the essential oil from Chenopodium ambrosioides L .;
b. in the usual way, pharmaceutically acceptable adjuvants are added to the extracts to obtain the desired formulations. 18. The method according to 17, in which the composition is obtained in the form of gelatin pills, the production method comprising the steps of:
dissolve the pharmaceutical gelatin and softener in distilled water and filter to obtain a gelatin solution;
solvate and dilute the essential oil from Chenopodium ambrosioides L. with vegetable oil to obtain a crude oil;
add crude oil and gelatin solution to the gelatin pill making device; and
gelatin pills with an oily liquid are obtained as contents. 19. The method of claim 18, wherein the emollient is selected from the group consisting of glycerin, xylitol, sorbitol, and hydrogenated corn extract. 20. The method according to 17, in which the composition is obtained in the form of self-emulsifying preparations, the production method comprising the steps of
mixing the prescribed dose of essential oil from Chenopodium ambrosioides L., rapeseed oil, surfactants or an additional secondary surfactant,
the mixture is heated in a water bath at a temperature of 30-80 ° C or using an ultrasonic apparatus and a homogeneous and transparent solution is obtained, from which preparations are then formed in the form of soft or hard capsules. 21. The method according to claim 20, in which the surfactant is selected from the group comprising a condensate of polyoxyethylene and castor oil, a condensate of polyoxyethylene and hydrogenated castor oil, polysorbate and phospholipid. 22. The method according to item 21, in which the condensate of polyoxyethylene and castor oil is selected from polyoxyethylene (35) castor oil and polyoxyethylene (60) castor oil, the condensate of polyoxyethylene and hydrogenated castor oil is selected from polyoxyethylene (35) hydrogenated castor oil and polyoxyethylene (60 ) hydrogenated castor oil, polysorbate is selected from polysorbate 60 and polysorbate 80, phospholipid is selected from the group consisting of egg yolk lecithin, soya lecithin, dipalmitoylphosphatidylcholine, distearoi lphosphatidylcholine and dimyristoylphosphatidylcholine. 23. The method according to claim 20, in which the secondary surfactant is selected from the group comprising ethanol, glycol, propanediol, n-butanol, isopropanol, polyglycol 4000 and polyglycol 6000. 24. The use of the Chenopodium ambrosioides L. extract according to any one of claims 1 to 5 or the medicinal compositions according to any one of claims 6 to 16 for the manufacture of drugs for the treatment of gastritis and peptic ulcer due to HP infection.

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