KR101076127B1 - Pharmaceutical composition for detoxifying toxic substances caused by smoking which comprises extract of alnus japonica as an active component - Google Patents

Abstract

The present invention relates to a smoking toxicity detoxifying pharmaceutical composition, and more particularly to a smoking toxicity detoxifying pharmaceutical composition as an active ingredient.

Description

Pharmaceutical composition for detoxifying toxic substances caused by smoking which comprises extract of alnus japonica as an active component}

The present invention relates to a composition for smoking toxicity detoxification. Specifically, it relates to a composition for smoking toxicity detox using tomato outpost extract.

Smoking is now known to be a risk factor for six out of eight major deaths worldwide, and by 2030 it is estimated that total deaths from smoking will exceed 8 million people per year (Mpower, 2008, WHO report on the global tobacco epidemic (WHO).

The smoking rate in Korea, especially adult males, is high compared to the world. In 2005, 52.3% of the adult males were smokers. This is 13th in 132 countries with data from WHO members (Mpower, 2008, WHO report on the global tobacco epidemic, WHO) and the highest among OECD countries (OECD health data, 2006). ).

 The main diseases caused by smoking include lung cancer, chronic obstructive pulmonary disease (COPD), coronary artery disease, stroke (cerebrovascular disease), heart attack, aortic aneurysm, circulatory disease (peripheral vascular disease, etc.), throat cancer, and oral cancer. (Suk-Joon Yoon et al., 2001, The Burden of Early Deaths due to Smoking in Korea, Journal of Preventive Medicine, Vol. 34, No. 3).

Tobacco smoke contains 4,000 species of toxic substances, including carcinogens, which are harmful to the human body, and the main harmful components are tar and nicotine, which are mixtures of various toxic substances.

Tar contains more than 2,000 types of toxic substances, of which 20 are known to be carcinogens, including dioxin, benzopyrene and dimethylnitrosamine (Shindongcheon, Toxic Chemicals in Tobacco Smoke, Published by Korea Non-Smoking Association.

Nicotine is nitrosamine-4- (methyl nitrosamino) -1- (3-pyridyl) -1-butanone (nitrosamine-4 (methyl nitrosamino) -1- (3-pyridyl) -1-butanone } As a precursor to nicotine, acute inhalation of nicotine causes symptoms such as pupil contraction, blurred vision, vomiting, dyspnea, increased secretions from saliva and respiratory tract, and decreased heart rate. Chronic arteriosclerosis, hypertension Cause disease (Brunneman, KD et al., J. Natl. Cancer Inst. 89: 868-73 (1996); Carmella, SG et al., Cancer Epidemiol Biomarkers Prev. 6: 113-20 (1997); Wynder , EL et al., Environ Health Perspect. 103 Suppl 8: 143-148 (1995)).

Green tea extract (Chung. FL Proc. Soc. Exp. Viol. Med. 220: 244-248 (1999); Fujiki, H. et al.) Is a substance that can alleviate and detoxify the toxicity of smoking by tar and nicotine. , Mutat. Res. 18: 307-310 (1998)), a mixture of a mixture extract (Korean Patent No. 0494223), Schisandra chinensis extract, Gilkyung extract, such as Eoseongcho, Pogongyoung, Licorice (Korea Patent Publication No. 2004-0102690) etc. can be mentioned.

The present invention also discloses a technique that can alleviate and detoxify the smoking toxicity caused by tar and nicotine using tomato starch extract and the like.

An object of the present invention is to provide a composition for smoking toxicity detoxification.

Other technical problems of the present invention will be presented below.

As the present inventors confirmed in the following Examples and Experimental Examples, we prepared the extracts of each ethanol aqueous solution of tomato outpost, birch, rowan, branch and alder and examined the nicotine degrading activity and tar toxicity removing activity of the extract , All of the extracts were confirmed to have the above activities. Wherein the nicotine degradation activity is described by Barlow et al. [Barlow R. D, Stone R. B., Clin. Chim. Acta., 165, pp45, 1987]. In virto and animal testing of changes in blood nicotine concentrations were confirmed. The elimination activity of tar toxicity was determined by Brunnemann et al. [Brunnemann, K.D. and Hoffiman D., Toxcol, 21, 235 (91)]. The present inventors further prepared a beverage containing all of the five extracts and performed the sensory evaluation by drinking the beverage, and most of the experimental participants were able to obtain an answer that the smell, sputum, cough and nausea were improved.

The present invention has been completed based on the experimental results, the present invention can be understood as a composition for smoking toxicity detoxification.

Smoking toxicity detoxification composition of the present invention is characterized in that it comprises at least one extract of tomato outpost extract, baekryeoksacho extract, rowan extract, branch extract and alder extract as an active ingredient.

As used herein, "smoking toxicity" refers to the toxicity caused by nicotine and / or tar, and thus smoking toxicity may be understood to have the same meaning as nicotine toxicity and / or tar toxicity.

In addition, the term "active ingredient" as used herein means a component that can exhibit the desired activity alone or in combination with a carrier that is not active itself.

In addition, in the present specification, "tomato starch extract" refers to tomato leaves, stems, flowers, roots or mixtures thereof regardless of the extraction method, methanol, ethanol, acetone, ethyl acetate, saturated normal butanol, chloroform, methylene chloride, water Or an extract obtained by extraction with a mixed solvent thereof and an extract fractionated with the solvents listed above in the extract. Regardless of the extraction method, as long as extraction is performed by immersing the tomato leaves, stems, flowers, roots or mixtures thereof, which are to be extracted, in the extraction solvent, the extraction method may be any method such as cooling, refluxing, heating, and ultrasonic wave. It should be understood that it can. Nevertheless, the "tomato outpost extract" is preferably obtained by extracting tomato leaves, stems, flowers, roots or mixtures thereof to be extracted with water, ethanol or a mixed solvent thereof, and the concentrated liquid extract from which the extraction solvent is removed. Or a solid extract.

In addition, in the present specification, "Oldenlandia diffusa" extract may be defined the same as the "tomato extract" except that the extract is a baekhwasa leaf, stem, flowers, roots or mixtures thereof.

In addition, in the present specification, "Lithospermum erythrorhizon" extract may be defined in the same manner as the "tomato extract", except that the extraction target is a branch, leaf, stem, flower, root or mixture thereof. Similarly, except that the extract is a rowan leaf, stem, flower, root or a mixture thereof, may be defined in the same manner as the "tomato extract", and the "duckwood extract" is similarly extracted. Except that the subject is alder leaves, stems, flowers, roots or mixtures thereof may be defined the same as the "tomato extract".

Other terms that are not specifically defined herein follow the Korean dictionary meaning or the meaning generally accepted in the art.

On the other hand, the composition for smoking toxicity detoxification of the present invention may contain any amount (effective amount) according to the purpose, formulation, compounding purpose, etc., as long as it can exhibit the detoxification activity of tomato toxic extract, such as an effective ingredient, the conventional An effective amount of phosphorus will be determined within the range of 0.001% to 99.900% by weight based on the total weight of the composition. An “effective amount” herein refers to an amount of active ingredient that can lead to the prevention, amelioration, treatment of smoking toxicity, or a delay in the expression of such toxicity. Such effective amounts can be determined experimentally within the range of ordinary skill in the art.

Smoking toxicity detoxification composition of the present invention, in addition to the tomato ethanol extract and the like as an active ingredient, may include a known natural product or compound known to have smoking toxicity detoxification activity to increase and enhance smoking toxicity detoxification.

Such natural products or compounds include black bean powder or extracts, pogongyoung powder or extracts, gold and silver powder or extracts, triticale powder or extracts, bladder powder or extracts, licorice powder or extracts, hawthorn powders or extracts, hardwood powders or extracts , Organo powder or extract, sewage powder or extract, jeonho powder or extract, clove powder or extract, moth powder or extract, aloe powder or extract, stevia powder or extract, and the like. The meaning of the extract in the above is as described in relation to the tomato outpost extract of the bar except for the extraction target. Such extracts may be obtained by mixing the extraction objects.

The composition of this invention can be grasped | ascertained by food compositions, such as a drink, a gum, and a jelly in a specific aspect.

The food composition of the present invention may include sweeteners, flavoring agents, bioactive ingredients, minerals, etc. in addition to the active ingredients.

Sweeteners may be used in amounts that give the food a suitable sweet taste, and may be natural or synthetic. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.

Flavoring agents can be used to enhance the taste or aroma, both natural and synthetic. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. The natural flavor may be obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or may be obtained from green tea leaves, round leaves, jujube leaves, cinnamon, chrysanthemum leaves, jasmine and the like. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. In some cases, synthetic flavoring agents may be used, and synthetic flavoring agents may include esters, alcohols, aldehydes, terpenes, and the like.

As the physiologically active substance, catechins such as catechin, epicatechin, gallocatechin, epigallocatechin, vitamins such as retinol, ascorbic acid, tocopherol, calciferol, thiamine, riboflavin, and the like can be used.

As minerals, calcium, magnesium, chromium, cobalt, copper, fluoride, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium, zinc and the like can be used.

In addition, the food composition of the present invention may contain a preservative, an emulsifier, an acidulant, a thickener, and the like, in addition to the sweetener.

Such preservatives, emulsifiers and the like are preferably added and used in very small amounts as long as the use to which they are added can be achieved. By trace amount is meant numerically expressed in the range of 0.0005% to about 0.5% by weight based on the total weight of the food composition.

Examples of preservatives that can be used include sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), and the like.

Emulsifiers that can be used include acacia gum, carboxymethylcellulose, xanthan gum, pectin and the like.

Examples of acidulants that may be used include lead acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, and the like. Such acidulant may be added so that the food composition is at an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to the purpose of enhancing taste.

Thickeners that can be used include suspending implements, sedimenters, gel formers, swelling agents and the like.

The composition of the present invention can be used as a pharmaceutical composition in a specific embodiment.

Pharmaceutical compositions of the present invention, in addition to its active ingredients, include pharmaceutically acceptable carriers, excipients, and the like, oral formulations (tablets, suspensions, granules, emulsions, capsules, syrups, etc.), parenteral formulations (sterile injectable aqueous solutions). Or oily suspensions), topical formulations (solutions, creams, ointments, gels, lotions, patches) and the like.

As used herein, "pharmaceutically acceptable" means that the subject of application (prescription) does not have more toxicity (adequately less toxic) than is applicable without inhibiting the activity of the active ingredient.

Examples of pharmaceutically acceptable carriers include lactose, glucose, sucrose, starch (such as corn starch, potato starch, etc.), cellulose, derivatives thereof (such as sodium carboxymethyl cellulose, ethylcellulose, etc.), malt, gelatin, talc, Solid lubricants (such as stearic acid, magnesium stearate, etc.), calcium sulfate, vegetable oils (such as peanut oil, cottonseed oil, sesame oil, olive oil, etc.), polyols (such as propylene glycol, glycerin, etc.), alginic acid, emulsifiers (such as TWEENS), wetting agents (Such as sodium lauryl sulfate), colorants, flavors, tableting agents, stabilizers, antioxidants, preservatives, water, saline, phosphate buffer solutions, and the like. The carrier may be selected from one or more of suitable pharmaceutical formulations according to the formulation of the pharmaceutical composition of the present invention.

Excipients may be selected and used according to the formulation of the pharmaceutical composition of the present invention, for example, when the pharmaceutical composition of the present invention is prepared with an aqueous suspending agent, suitable excipients are sodium carboxymethyl cellulose, methyl cellulose, hydropropylmethylcellulose And suspending agents and dispersing agents such as sodium alginate and polyvinylpyrrolidone. Suitable excipients when prepared from injection solutions include Ringer's solution, isotonic sodium chloride, and the like.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and in some cases, can be administered topically.

The daily dose of the pharmaceutical composition of the present invention is usually 0.001 to 150 mg / kg body weight, and may be administered once or several times. However, since the dosage of the pharmaceutical composition of the present invention is determined in view of various related factors such as the route of administration, the age, sex, weight of the patient, and the severity of the patient, the dosage may limit the scope of the present invention in any aspect. It should not be understood as.

As described above, according to the present invention can provide a composition for smoking toxicity detox using tomato outpost extract and the like. The composition of the present invention can be used as a food composition or pharmaceutical composition, such as gum, beverages.

Figure 1a is a laboratory test result showing the nicotine removal activity of tomato outpost extract.
Figure 1b is a laboratory test result showing the nicotine removal activity of the baekhwasachocho extract.
Figure 1c is a laboratory test result showing the nicotine removal activity of rowan extract.
Figure 1d is a laboratory test result showing the nicotine removal activity of the branch extract.
Figure 1e is a laboratory test result showing the nicotine removal activity of the alder extract.

Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.

<Example> Preparation of tomato outpost, bleaching saseolcho, Rowan, tired or alder extract

Example 1 Preparation of Tomato Outpost Extract

1 kg of tomato starch (leaves, stems, and roots) is immersed in 5 L of 50% ethanol, extracted for 10 hours at a temperature of 50 ° C., and extracted with residues. Got it.

<Example 2> Preparation of Baengsasasulchocho extract

1 kg of cuttlefish leaves, stems, and roots of baekhwa sage were immersed in 5 L of 50% ethanol, extracted for 10 hours at a temperature of 50 ° C., the residue was extracted, and concentrated in black and white to remove the extraction solvent to obtain a solid extract. .

Example 3 Preparation of Rowan Extract

1 kg of the leaves, stems, and roots of rowan were immersed in 5 L of 50% ethanol, extracted for 10 hours at a temperature of 50 ° C., the residue was extracted, and concentrated under reduced pressure to remove the extraction solvent to obtain a solid extract. .

Example 4 Preparation of Branch Extract

1 kg of the branched leaves, stems, and roots were immersed in 5 L of 50% ethanol, extracted for 10 hours at a temperature of 50 ° C., and the extraction residues were removed.

Example 5 Preparation of Alder Extract

1 kg of alder leaves, stems, and roots were immersed in 5 L of 50% ethanol, extracted for 10 hours at a temperature of 50 ° C., and the extraction residues were removed. .

Preparation Example Preparation of Mixed Drink

To prepare a beverage comprising the extract of the <Examples 1 to 5> with the ingredients and compositions as shown in Table 1 below.

Ingredients and Compositions of Beverages Content (% by weight) Extract of Example 1 2.0 Extract of Example 2 2.0 Extract of Example 3 2.0 Extract of Example 4 2.0 Extract of Example 5 2.0 honey 10.0 Grapefruit Seed Extract (Natural Preservative) 1.0 Purified water Balance (to 100)

Experimental Example: Nicotine Decomposition Effect, Tar Toxicity Removal Effect, Sensory Evaluation

Experimental Example 1 Nicotine Degradation Effect Experiment

<Experimental Example 1-1> In vitro (In in vitro )

The method presented by Barlow et al. For a laboratory experiment on the nicotine degradation effect of the extract of the above example [Barlow R. D, Stone R. B., Clin. Chim. Acta., 165, pp45, 1987] was applied as follows.

200 μl of 1 mM nicotine (Sigma Co., USA) and the same amount of 10% (w / v) of each example extract (dissolved in distilled water) were added to a microtube (5 mL). (0, 10, 20, 30, 60 and 90 minutes) The amount of cotinine, a degradation product of nicotine, was measured. As a control, 200 µl of distilled water and 200 µl of 1 mM nicotine were mixed in place of the extract of Example. Next, 100 μl of 4M sodium acetate buffer (pH4.7), 40 μl of 1.5 M potassium cyanate, 40 μl of 0.4 M chloramine-T, 50% (v / v) aceto 200 μl of 78 mM barbituric acid dissolved in nitrile was added sequentially and mixed for 10 seconds. The mixture was reacted at room temperature for 15 minutes, and 1M sodium metabisulphite 40 After stopping the reaction with ㎕, the absorbance at 490 nm was measured to determine the amount of change in cotinine. All experiments were performed three times each and the results are shown in FIGS. 1A-1E with MEAN ± SD. Referring to Figures 1A to 1E it can be seen that the extracts of the above examples all convert nicotine to cotinine over time.

Experimental Example 1-2 Animal Experiment

The experimental animals purchased rats without Sprague-Dawley-type specific pathogens weighing 260-280g, 6 weeks old {Central Laboratory Animals, South Korea} and the temperature was 21 ± 2 ℃ and lighting time 12L / 12D in the animal breeding room before the experiment started. A sufficient amount of water and solid feed were provided, and 5 dogs were separated and adapted to the test environment for 2 weeks.

The experimental animals were divided into 6 groups (1 group: control group, 5 groups: experimental group) of 5 animals, and the experimental group was mixed with a solid feed at 1.0 g / kg / day and mixed with water for 7 days. After administration, nicotine was intraperitoneally administered at 3 mg / kg, and the control group was intraperitoneally administered at only 3 mg / kg of nicotine without administering the extract of Example. Then, 1 ml of blood was drawn from the heart to measure the concentration of nicotine in the blood. To measure the concentration of nicotine, the blood was adjusted to pH 9.0 with dilute ammonia water, then maintained in an EXTRELUT COLUMN (Merk) for 15 minutes, eluted with 15 ml of ethyl acetate, and the eluted acetate was distilled under reduced pressure and distillation. After removal, 100 µl of ethyl acetate was added to the resulting powder to dissolve to prepare an analytical sample. Analysis was performed using gas chromatography (Gas Chromatography-Mass Spectrometer, FISONS Instruments Co.).

The nicotine concentration in blood is shown in Table 2 below with MEAN ± SD.

Blood nicotine concentration division Blood Nicotine Concentration (µg / ml) Experiment 1 1.20 ± 0.13 Experiment 2 1.74 ± 0.15 Experiment group 3 1.72 ± 0.09 Experimental Group 4 1.93 ± 0.12 Experimental group 5 1.64 ± 0.13 Control group 2.28 ± 0.12 * Experimental groups 1 to 5 are experimental groups to which the extracts of Examples 1 to 5 were administered, respectively.

Experimental Example 2 Tar Toxicity Removal Effect Experiment

Experiments on the elimination of tar toxicity of the extracts of each example were carried out by Brunnemann et al. [Brunnemann, K.D. and Hoffiman D., Toxcol, 21, 235 (91)] was applied as follows.

Five animals were used as the experimental group of 1 group, and the animals were intraperitoneally administered with tar at a dose of 30 mg / kg / 10ml, and then the extract of each of the above examples was administered at the dose of 1.0g / kg / 1 day. Oral administration together for 7 days was observed for survival. The control group was administered distilled water instead of the extract of the example.

The results are shown in <Table 3> below as the number of people who died for 7 days.

The number of the dead division The number of the dead Total number of survivors 1 day 2 days 3 days 4 days 5 days 6 days 7 days Experiment 1 0 0 0 0 0 0 0 5 Experiment 2 0 0 0 0 0 One 0 4 Experiment group 3 0 0 0 0 0 One One 3 Experimental Group 4 0 0 0 0 One One 0 3 Experimental group 5 0 0 0 0 0 One One 3 Control group 0 0 One 0 One One One One

Experimental Example 3 Sensory Evaluation Experiment

Using the beverage of the preparation example was performed to improve the symptoms according to the smoker smoking as follows.

One hundred smokers of one or more packs of adult men and women were selected per day to drink the beverages of the preparations twice a day for one month. One-time volume was 140 ml.

Metrics were significantly improved (5 points), greatly improved (4 points), moderate improvement (3 points), slight improvement (2 points) using the five-point scale method for four items: bad breath, sputum, cough and nausea. , No effect (0 points), and the results were shown in <Table 4>.

Nicotine Degradation Effect (Unit: Persons) division Greatly improved Greatly improved Improvement Slightly improved no effect Bad breath 72 18 4 4 2 Phlegm 68 21 6 3 2 cough 54 26 10 5 5 nausea 66 14 14 4 2

The results show that the beverage of the present invention significantly improves the symptoms of smoking.

Claims (2)

Smoking toxicity detoxification pharmaceutical composition comprising alder extract as an active ingredient. The method of claim 1,
The alder extract is a tobacco toxic detoxification pharmaceutical composition, which is obtained by dipping the alder leaves, stems, flowers, roots or mixtures thereof in 50% ethanol for 10 hours at 50 ° C. .

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