JP5546833B2 - Acetaldehyde / ethanol reducing agent - Google Patents

Description

  The present invention relates to an acetaldehyde and ethanol reducing agent. More specifically, the present invention relates to an acetaldehyde and ethanol reducing agent containing, as an active ingredient, a natural product-derived component that exhibits an action of reducing acetaldehyde concentration and / or ethanol concentration in breath and / or blood after drinking.

  When a person drinks, a “drunk” state is caused. This is thought to be because ethanol is absorbed into the body and reaches the brain, causing a paralyzed state of the brain. Then, excessive drinking or the like causes a “drunk” state (paralysis of the brain) to occur, which causes various problems such as “drunk sickness” by losing normal judgment and motor function. When the body modulation or discomfort is carried over to the next day, it is a so-called “hangover”. Various drugs and foods have been proposed in order to suppress such discomfort caused by drinking, but there are very few that are sufficiently satisfactory from the viewpoint of safety and effects.

  Regarding the metabolic pathway of ethanol in the body, about 20% is first absorbed in the stomach, and the remaining about 80% is absorbed in the small intestine and sent to the liver. Here, it is decomposed into acetaldehyde by the action of alcohol dehydrogenase, and further oxidized by the action of acetaldehyde dehydrogenase to change into acetic acid. Ethanol and acetaldehyde that could not be decomposed by the liver travel to the whole body including the brain, and then return to the liver to be decomposed again. Some of these ethanol and acetaldehyde are discharged from the body by being contained in urine, sweat, and exhalation without being metabolized in the body.

  Acetaldehyde, an intermediate substance in ethanol metabolism, is highly toxic. If ethanol metabolism is insufficient and acetaldehyde remains in the body, symptoms such as headache, nausea and palpitation occur. Therefore, acetaldehyde is considered to be a causative agent of unpleasant feelings such as “drunkenness” and “hangover”, and it is said that about half of the people in Japan have a low ability of acetaldehyde dehydrogenase to degrade this acetaldehyde. .

  Therefore, in particular in Japan, there are pharmaceutical ingredients and pharmaceuticals that have the effect of reducing the ethanol concentration and acetaldehyde concentration in the body to suppress the discomfort etc. that occur with drinking, are highly safe and sufficiently satisfactory. Development has been sought for many years.

  On the other hand, fucoidan, which is one of the dietary fibers, is Okinawa Mozuku (Cladosiphon okamuranus), Thread Mozuku (Fine Mozuku Mosque: Nemacistus decipieus), and thick Mozuku (Tinocitahicus). Is a heterosulfated polysaccharide composed of fucose having a molecular weight of several hundreds of thousands, which is present in brown algae such as Kjellmaniella crassifolia and Kunabu (Undaria pinnatifida), and is a safe function derived from seaweed with abundant food experience In recent years, it has attracted attention as a natural ingredient. In addition, development of a low-molecular fucoidan in which fucoidan is reduced in molecular weight by an enzyme or the like, and development of a food such as a functional food using the low-molecular fucoidan are underway.

  Examples of drugs utilizing the physiological function of fucoidan include an antitumor agent (Patent Document 1), an inflammatory bowel disease preventive and therapeutic agent (Patent Document 2), an anticancer side effect inhibitor (Patent Document 3), a gastric cancer cell growth inhibitor ( Patent Literature 4), antiviral agents (Patent Literature 5), therapeutic agents for atopic dermatitis (Patent Literature 6), and the like are disclosed. However, there have been no reports on the concentration of ethanol in the body as a physiological function of fucoidan, the effect of reducing acetaldehyde concentration, and a drug (pharmaceutical composition) containing fucoidan as an active ingredient utilizing this effect.

JP 7-138166 A JP 2003-146888 A JP 2004-75595 A JP 2006-306897 A JP 2007-217410 A JP 2008-44913 A

  An object of the present invention is to provide a pharmaceutical ingredient and a pharmaceutical product (pharmaceutical composition) that reduce the acetaldehyde concentration and ethanol concentration in the breath and / or blood after drinking. The object is to suppress and prevent discomfort during drinking and / or after drinking (including acute discomfort, such as “sickness” associated with drinking, “hangover” the day after drinking).

  In order to achieve the above object, the present inventors have focused on fucoidan derived from mozuku as a result of intensive studies. And by orally administering this for a certain period of time before drinking, the active ingredient is a highly safe substance derived from a natural product with abundant dietary experience. Alternatively, the inventors have found that it is possible to provide a reducing agent for both acetaldehyde and ethanol concentration in blood, or a reducing agent for either acetaldehyde or ethanol concentration, and the present invention has been achieved. In addition, a novel measurement method was also found to qualitatively and quantitatively determine the concentration of acetaldehyde and ethanol in exhaled breath by gas chromatography alone.

That is, the embodiment of the present invention is as follows.
(1) A breath and / or blood and / or urine acetaldehyde and / or ethanol concentration-reducing agent (medicine for reducing the same), characterized by containing mozuku-derived fucoidan as an active ingredient.
(2) By oral administration, in an amount of 10 to 5000 mg (preferably 200 to 4500 mg, more preferably 280 to 840 mg) in terms of dry weight of fucoidan 10 to 60 minutes before drinking (preferably 20 to 40 minutes). An agent for pre-drink administration according to (1) (10-5000 mg oral administration for pre-drink administration), which is administered.
(3) The agent according to (1) or (2), wherein the mozuku-derived fucoidan is a hot water extract of mozuku and / or a processed product thereof.
(4) The agent according to (3), wherein the hot water extract of Mozuku is a liquid obtained by heating a mixture of Mozuku and water and then filtering the mixture, and desalting the obtained filtrate.
(5) The agent according to (3) or (4), wherein fucoidan derived from mozuku is a purified product obtained by further purifying a hot water extract of mozuku and / or a processed product thereof.
(6) In any one of (3) to (5), the treated product is at least one selected from a concentrate, a paste, a dried product, an emulsion, a liquid, and a diluted product. The agent described.
(7) The mozuku-derived fucoidan is a high-molecular fucoidan having a molecular weight of 50,000 or more and has a sulfate group content of 10 to 20%, as described in any one of (1) to (6) Agent.
(8) The agent according to any one of (1) to (7), wherein the mozuku is at least one of yarn mozuku, thick mozuku, and Okinawa mozuku.
(9) Qualitatively and quantitatively determine the concentration of acetaldehyde and ethanol in exhaled breath at a time by quantitatively fixing the exhaled breath to a cold trap in a column cooled with liquid nitrogen and then measuring by gas chromatography. Method for measuring acetaldehyde and ethanol concentration in exhaled breath.

  According to the present invention, an agent containing mozuku-derived fucoidan as an active ingredient is orally administered before drinking, thereby reducing the acetaldehyde and / or ethanol concentration in the breath and / or blood after drinking. Can suppress and / or prevent discomfort during drinking and / or after drinking (including acute discomfort, for example, “sickness” associated with drinking, “hangover” the day after drinking, etc.). The present invention is extremely effective not only in reducing either acetaldehyde or ethanol in breath and / or blood and / or urine (at least one of these three), but also in reducing both acetaldehyde and ethanol. It is characteristic. Mozuku-derived fucoidan is an ingredient derived from natural products obtained from seaweed with abundant dietary experience, so it provides extremely safe drugs with very little risk of side effects such as continuous or excessive intake. It becomes possible. Furthermore, by using the component measurement method in exhaled breath of the present invention, it becomes possible to measure the qualitative and quantitative determination of acetaldehyde and ethanol in exhaled at a time by gas chromatography alone.

The acetaldehyde integrated amount in expiration | expired_air of the test subject (A, B) in the alcohol tolerance test I (the integrated amount in expiration | expired_air which was extract | collected and measured after drinking) is shown. In addition, AUC (Area of under curve) is an area under the curve, and the area under the curve of the graph (line graph) obtained from the peak area of the gas chromatography at each measurement time was calculated as an integrated amount (hereinafter referred to as the integrated amount). This is also the case for the graph). The ethanol accumulation amount in the expiration | expired_air of the test subject (A, B) in the alcohol tolerance test I (The accumulation amount in the expiration | expired_air which was extract | collected and measured after drinking) is shown. The time-dependent change of the acetaldehyde amount in the expiration | expired_air of the test subject (10 persons) in the alcohol tolerance test II is shown (** has a significant difference at p <0.01). In addition, the peak area of the gas chromatography was used as the component amount in the collected breath (the same applies to the following graphs). The acetaldehyde integrated amount in the exhaled breath of subjects (10 persons) in the alcohol tolerance test II (the integrated amount in the exhaled breath collected and measured after drinking) is shown. The time-dependent change of the amount of acetaldehyde in the serum of the test subject (10 persons) in the alcohol tolerance test II is shown (* is significantly different at p <0.05). 1 shows the cumulative amount of acetaldehyde in the serum of subjects (10 subjects) in the alcohol tolerance test II (the cumulative amount in serum collected and measured after drinking). The time-dependent change of the ethanol amount in the expiration | expired_air of the test subject (10 persons) in the alcohol tolerance test II is shown (** is significantly different at p <0.01). The accumulated amount of ethanol in the exhaled breath of subjects (10 persons) in the alcohol tolerance test II (the accumulated amount in expired air collected and measured after drinking) is shown. The time-dependent change of the ethanol amount in the serum of the test subject (10 persons) in the alcohol tolerance test II is shown (* is significantly different at p <0.05). 1 shows the cumulative amount of ethanol in the serum of subjects (10 subjects) in the alcohol tolerance test II (the cumulative amount of serum collected and measured after drinking).

  Hereinafter, the present invention will be described in detail.

  In the present invention, mozuku-derived fucoidan is used. The mozuku is preferably an Okinawa mozuku (Cladosifon okamuranus), a thread mozuku (fine mozuku) (Nemocystus decipeius), or a thick mozuku (Tinocladia crassa).

  Mozuku-derived fucoidan can be used as a purified fucoidan product (including commercial products) extracted, isolated and purified from mozuku, as well as a hot water extract of mozuku and its processed product. Although not limited to this, the Mozuku-derived fucoidan has a molecular weight of 50,000 or more, preferably 100,000 or more, more preferably 200,000 to 500,000 (for example, 250,000 to 350,000) based on pullulan. It is desirable that the sulfate group content be 10% to 20%, preferably 11% to 17%, and more preferably 13% to 14%.

  In order to extract the extract of the present invention from mozuku, it is adjusted to acidic (pH 3.0 to 6.0) with an aqueous acetic acid solution or hydrochloric acid, and is 50 ° C. or higher, preferably 60 to 100 ° C., more preferably 60 to 90. After extraction of fresh mozuku (which may be cut, pasted, dried or frozen) using hot water at 60 ° C., for example 60 to 75 ° C. for 30 minutes to 3 hours (for example, 100 ° C. for 45 minutes in an autoclave) After treatment for ˜1 hour 30 minutes), the resulting extract is desalted by electrodialysis. The hot water extract of the present invention includes an extract obtained by simply extracting mozuku with hot water as described above, its filtrate, and an extract obtained by further desalting the above (etc.). Also included are purified products purified by quaternary ammonium salt treatment, alcohol precipitation, ion exchange resin chromatography, gel filtration chromatography, ultrafiltration, ultrafine filtration, and the like.

  In the present invention, a processed product of mozuku hot water extract can also be used. Examples of the treated product include concentrates, pasted products, dried products (spray dried products, freeze dried products, vacuum dried products, drum dried products, etc.), emulsions, liquid products, and diluted products. Especially for dry matter, the weight is lightest and the volume is small, so it is highly suitable for manufacturing and processing, can reduce transportation costs, and is easy for users of fucoidan-containing agents to travel long distances, that is, when traveling. It is a processed product that can be ingested.

  The effective intake of mozuku-derived fucoidan is suitably 10 to 5000 mg, preferably 200 to 4500 mg, more preferably 280 to 840 mg orally administered in terms of dry weight of fucoidan. As for the timing of ingestion, it is appropriate to administer once or two to three times 10 to 60 minutes before drinking, preferably 20 to 40 minutes before (around 30 minutes before drinking). . In addition, ingestion immediately before drinking (for example, within 5 minutes before) is not preferable because a satisfactory effect cannot be obtained.

  Mozuku-derived fucoidan is administered in various forms. As the administration form, in addition to oral administration of mozuku extract and its concentrate as it is, oral administration such as tablets (tablets), capsules, granules (fine granules), powders, syrups and the like can be mentioned. it can. These various preparations are usually used in the pharmaceutical formulation technical field such as excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspension agents, coating agents, etc. It can be formulated with known adjuvants. For example, a preparation containing 10 to 5000 mg in terms of fucoidan dry weight can be used as the active ingredient (active ingredient), but if necessary, it may be divided into 1 to several doses.

  The mozuku-derived fucoidan, which is the active ingredient of the present invention, is derived from seaweed with abundant dietary experience, so there is no problem with regard to safety. This indicates that it can be used without problems for healthy people, people with normal physical strength and resistance, as well as those who are considered to have lower physical strength and resistance than normal people, such as seniors. ing.

  In the present invention, a novel method for measuring acetaldehyde and ethanol concentrations in exhaled breath is also provided. In component analysis, measurement by gas chromatography is often performed, but this can relatively ensure quantitativeness when a liquid is used as a sample, but quantitative measurement is impossible because a predetermined amount of gas cannot be reliably injected. It was thought. In the measurement method of the present invention, the exhaled gas is fixed and fixed in a cold trap in a column cooled with liquid nitrogen, and then the gas is instantaneously vaporized and then measured by gas chromatography to ensure quantitativeness. Allows qualitative and quantitative determination of components at once. According to this measurement method, the detection target component can be measured as a sharp peak.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

(Example 1: Production of mozuku-derived fucoidan)
In the alcohol load tests shown in Examples 2 and 3, “Polymer Fucoidan Sea Algaev (registered trademark)” which is a seafood kimura or product was used as a mozuku-derived fucoidan. This product was manufactured as follows.

Okinawa mozuku (Cladosiphon okamuranus) was used as the mozuku. This mozuku was suspended in 1 to 5 times its wet weight of water and adjusted to acidic by adding an acetic acid aqueous solution. Subsequently, the mixture was kept heated at 60 to 90 ° C. to elute fucoidan, and then centrifuged to remove precipitates. Fucoidan was concentrated and desalted by removing low molecular components from the supernatant by electrodialysis to obtain mozuku-derived fucoidan.
The molecular weight of the obtained mozuku-derived fucoidan was about 300,000 as a converted molecular weight based on the pullulan molecular weight, and the sulfate group content was 13%.

(Example 2: Alcohol tolerance test I)
In order to confirm the effects of ingestion of mozuku-derived fucoidan on the concentration of acetaldehyde in breath and ethanol concentration after drinking, the following alcohol tolerance test was performed.

Two subjects (A and B) were tested on an empty stomach under fasting conditions (minimum intake of water).
First, 30 ml of mozuku-derived fucoidan (840 mg in terms of fucoidan dry weight) was ingested 30 minutes before the start of the test. Then, the test was started 30 minutes later, A drunk 2 sakes (alcohol 15 degrees) and B drunk 3 sakes (alcohol 15 degrees) in 5 minutes each. A was collected every 1, 2, 4, 6 hours from the start of drinking, and B was collected 1 L each every 1, 3, 5, 7, 9, 11 hours from the start of drinking. As a control, the same subject was subjected to an alcohol tolerance test in the same manner as described above without ingesting mozuku-derived fucoidan before the start of the test.

  The concentration of the collected exhaled breath was measured by gas chromatography (GC) by the following method.

  The collected exhaled breath 100 mL was adsorbed on the adsorption column in 5 minutes. After the GC capillary column inlet portion was cooled with liquid nitrogen, the adsorption column was heated at the injection portion for 15 minutes, and the adsorbed gas was expelled into the capillary column (the gas was in the middle of the liquid nitrogen portion (cold trap)). Fixed). After 15 minutes, the capillary column is taken out from the liquid nitrogen (the gas evaporates instantly), and the capillary column is heated at 30 ° C. until 10 minutes after the start of the measurement, and thereafter the temperature is increased to 250 ° C. at a rate of 20 ° C. per minute. Measured by heating.

  Looking at the measurement results, in each subject, intake of mozuku-derived fucoidan before ingestion reduced the acetaldehyde and ethanol concentrations in the breath each time after drinking by 10 to 90% compared to when no fucoidan was ingested. It was confirmed. Moreover, even if it compares by both the amount of acetaldehyde in expiration | expired_air, and the ethanol amount integrated value, the reduction effect by ingestion of fucoidan before drinking was confirmed (FIG. 1, FIG. 2). From these results, it was confirmed that ingestion of mozuku-derived fucoidan before drinking was effective in reducing the concentration of acetaldehyde and ethanol in breath after drinking.

  It is known that the concentration of acetaldehyde and ethanol in the breath correlates with the concentration of acetaldehyde and ethanol in the blood (for example, “Proper Drinking Guidebook” supervised by the Mental Health Division, Health and Medical Bureau, Ministry of Health and Welfare, Alcohol Health Medical Association) , June 1991, p. 28). That is, a low acetaldehyde / ethanol concentration in the breath means a low acetaldehyde / ethanol concentration in the blood. Therefore, the above test results indicate that intake of mozuku-derived fucoidan before drinking is effective in reducing blood acetaldehyde concentration and ethanol concentration.

  In addition, when the same alcohol tolerance test was done by ingesting mozuku-derived fucoidan 5 minutes before drinking, an acetaldehyde and ethanol concentration reduction effect was not recognized. Therefore, it was shown that in order to exert the effect of reducing the acetaldehyde concentration and ethanol concentration of mozuku-derived fucoidan, it is necessary to take it preferably about 30 minutes before drinking.

(Example 3: Alcohol tolerance test II)
In order to confirm the effects of ingestion of mozuku-derived fucoidan on the acetaldehyde concentration and ethanol concentration in exhaled breath and serum after drinking, the following alcohol tolerance test was performed.

The test was performed on 10 subjects (age: 20-60s) under conditions that would make them hungry at the start of the test. Specifically, the subjects were allowed to eat the same menu (without alcohol) from lunch on the test day, and the test was started when 6 hours passed after lunch.
First, 30 ml of each mozuku-derived fucoidan (840 mg in terms of fucoidan dry weight) was ingested 30 minutes before the start of the test. Then, after 30 minutes, the test was started, and each person ingested two sakes (alcohol content of 15 degrees) for 10 minutes. Immediately after the start of drinking (0 hour) and every 2, 4, 6, and 14 hours after the start of drinking, 1 L of exhaled gas and 20 ml of blood were collected. In addition, after expiration and blood collection 2 hours after the start of the test, the subjects were allowed to eat a meal of the same menu (without alcohol). As a control, the same subject was subjected to an alcohol tolerance test in the same manner as described above without ingesting mozuku-derived fucoidan before the start of the test. The acetaldehyde and ethanol concentrations in exhaled breath were measured in the same manner as in Example 2, and the acetaldehyde and ethanol concentrations in serum were measured by a conventional method.

As a result, it was confirmed that the concentration of both acetaldehyde and ethanol was reduced both in each measurement time and in the total amount (integrated amount) by ingesting fucoidan (FIGS. 3 to 10). What was particularly remarkable was the concentration of acetaldehyde in exhaled breath after 4 hours of drinking and the concentration of ethanol in exhaled breath after 2 hours of drinking, and a very significant difference was observed depending on the presence or absence of fucoidan (p <0.01). . Also, a significant difference was observed in the serum acetaldehyde concentration 6 hours after drinking and the serum ethanol concentration 2 hours after drinking depending on the presence or absence of fucoidan (p <0.05).
Therefore, the above test results indicate that intake of mozuku-derived fucoidan before drinking is very effective in reducing acetaldehyde concentration and ethanol concentration in exhaled breath and serum after drinking.

(Example 4: Production of fine granules)
As mozuku-derived fucoidan, 70 parts by weight of mozuku-derived fucoidan (dried powder) obtained by spray-drying “polymer fucoidan Sea Algaf (registered trademark)” described in Example 1, 20 parts by weight of lactose, and 10 parts by weight of corn starch are mixed. The obtained mixture was fluidized-bed granulated with a 5% aqueous solution of hydroxypropylmethylcellulose to obtain a fine granule.

(Example 5: Manufacture of tablets)
As mozuku-derived fucoidan, 10 parts by weight of mozuku-derived fucoidan (dried powder) obtained by spray-drying “polymer fucoidan Seeargaev (registered trademark)” described in Example 1, 80 parts by weight of crystalline cellulose, 8 parts by weight of whey calcium, 2 parts by weight of glycerin fatty acid ester was mixed and tableted by tableting to a particle shape of φ7 mm and a particle weight of 200 mg.

  The present invention is summarized as follows.

  The present invention relates to pharmaceutical ingredients and pharmaceuticals (pharmaceutical compositions) for reducing exhalation and / or blood acetaldehyde concentration and ethanol concentration during drinking, thereby suppressing and preventing discomfort after drinking and drinking. The purpose is to provide.

  And, by using mozuku-derived fucoidan as an active ingredient, it is possible to provide a novel aspirating and / or blood acetaldehyde and / or ethanol concentration reducing agent at the time of drinking, which has an excellent effect. Since the present invention uses a substance derived from a natural product with abundant experience as an active ingredient, there is no problem in safety.

Claims (6)

A polymer fucoidan molecular weight from 250,000 to 350,000, and sulfate group content contained as an active ingredient a mozuku fucoidan is 10-20%, by oral administration, fucoidan dry weight 20 to 40 minutes before drinking An acetaldehyde and ethanol concentration-reducing agent in exhaled breath and / or blood and / or urine, which is used so as to be administered in an amount of 10 to 5000 mg in terms of conversion .   The agent according to claim 1, wherein the mozuku-derived fucoidan is a hot water extract of mozuku and / or a processed product thereof.   The agent according to claim 2, wherein the hot water extract of mozuku is a liquid obtained by heating a mixture of mozuku and water and then filtering the mixture, and desalting the obtained filtrate.   The agent according to claim 2 or 3, wherein fucoidan derived from mozuku is a purified product obtained by further purifying a hot water extract of mozuku and / or a processed product thereof.   The agent according to any one of claims 2 to 4, wherein the treated product is at least one selected from a concentrate, a paste, a dried product, an emulsion, a liquid, and a diluted product.   The agent according to any one of claims 1 to 5, wherein the mozuku is at least one of yarn mozuku, thick mozuku and Okinawa mozuku.

Images