AU680674B2 - Composition for treatment of hangovers - Google Patents
Composition for treatment of hangovers Download PDFInfo
- Publication number
- AU680674B2 AU680674B2 AU73779/94A AU7377994A AU680674B2 AU 680674 B2 AU680674 B2 AU 680674B2 AU 73779/94 A AU73779/94 A AU 73779/94A AU 7377994 A AU7377994 A AU 7377994A AU 680674 B2 AU680674 B2 AU 680674B2
- Authority
- AU
- Australia
- Prior art keywords
- subjects
- composition
- composition according
- alcohol
- methionine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 239000000203 mixture Substances 0.000 title claims description 33
- 206010019133 Hangover Diseases 0.000 title claims description 28
- 238000011282 treatment Methods 0.000 title description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 49
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 19
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 19
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 19
- 229960003767 alanine Drugs 0.000 claims description 19
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 18
- 229960004452 methionine Drugs 0.000 claims description 18
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 claims description 16
- 229930195722 L-methionine Natural products 0.000 claims description 16
- 208000024891 symptom Diseases 0.000 claims description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 5
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 239000004150 EU approved colour Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000013355 food flavoring agent Nutrition 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000007968 orange flavor Substances 0.000 claims description 3
- 238000004040 coloring Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 238000012360 testing method Methods 0.000 description 29
- 229940068196 placebo Drugs 0.000 description 26
- 239000000902 placebo Substances 0.000 description 26
- 206010028813 Nausea Diseases 0.000 description 22
- 230000008693 nausea Effects 0.000 description 22
- 206010019233 Headaches Diseases 0.000 description 21
- 231100000869 headache Toxicity 0.000 description 21
- 206010000059 abdominal discomfort Diseases 0.000 description 19
- 206010000087 Abdominal pain upper Diseases 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 230000037406 food intake Effects 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 7
- 239000002253 acid Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- 230000035622 drinking Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 235000005550 amino acid supplement Nutrition 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000001769 parametric statistical test Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010053155 Epigastric discomfort Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 description 1
- -1 L-methionine L-alanine Citric acid Chemical compound 0.000 description 1
- OFPOBWHATCWYLY-RJMJUYIDSA-N OC(=O)CC(O)(C(O)=O)CC(O)=O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](O)C(O)O[C@@H]1CO Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](O)C(O)O[C@@H]1CO OFPOBWHATCWYLY-RJMJUYIDSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 208000018316 severe headache Diseases 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Processing Of Solid Wastes (AREA)
- Detergent Compositions (AREA)
Description
WO 95/04529 PCT/AU94/00461 -1- COMPOSITION FOR TREATMENT OF HANGOVERS This invention relates to a composition which may be used to treat hangovers and which may be used to prevent or reduce hangovers. In particular, the invention is directed toward preventing or reducing the symptoms of alcohol-induced hangovers.
Hangovers which result from the over indulgence of alcohol are believed to have two basic causes. The first of these is the diuretic effect of ethanol, caused by inhibition of release of endogenous antidiuretic hormone. The result of this diuretic effect is dehydration, which may be overcome by ingestion of large amounts of water following consumption of alcohol.
The second cause of hangovers is the toxic effect of acetaldehyde on the body. The major route for elimination of alcohol is by conversion of ethanol in the liver by alcohol dehydrogenase to produce acetaldehyde.
Increase in water consumption has little effect on the elimination of alcohol or acetaldehyde from the body, and hence little effect on this cause of hangover.
The present invention aims to provide a composition which is useful in preventing or reducing the effects of hangovers. It further aims to provide a method of preventing or reducing the effect of hangovers.
In Alcoholism 13, 164-71 (1989), Tabakoff, Eriksson and von Wartburg show that methionine ingestion can lower circulating levels of acetaldehyde after ethanol ingestion in mice, rats and humans. The mechanism for this effect is not known, but since liver and serum levels of acetaldehyde are reduced without concurrent reduction in ethanol concentration, it is believed that methionine may increase the clearance of acetaldehyde.
Another amino acid which affects acetaldehyde metabolism is L-alanine. L-alanine has been shown to prevent acute toxicity of acetaldehyde in mice (Fujiwara, Suwa, Yoshizumo, Yamatodani and Wada; Arukoru Kenkyuto Iakubutsu Ison, (1988) 23, 58-69).
It has now surprisingly been discovered that I- ~L WO 95/04529 PCT/AU94/00461 -2byadministering a composition containing both L-methionine and L-alanine in conjunction with alcohol consumption, the effects of a hangover may be alleviated or prevented. The effect of this composition is beyond that expected for the combined individual effects of L-methionine and L-alanine, showing a synergy of effect.
Accordingly, the present invention provides a composition for reducing the symptoms of hangover, including therapeutically effective amounts of L-methionine and L-alanine, or pharmaceutically acceptable salts thereof as active ingredients.
It is preferred that the weight ratio of L-methionine to L-alanine is from 1:2 to 2:1 to maximize the effectiveness of the composition.
In a preferred form of the invention, a composition containing substantially equal quantities by weight of L-methionine and L-alanine as active ingredients is prepared. The composition may also contain known pharmaceutically acceptable excipients. In a particularly preferred embodiment, an effervescent composition is prepared containing, in addition to the active ingredients, effervescing agents (for example citric acid anhydrous and sodium bicarbonate), surfactants and wetting agents (for example sodium lauryl sulphate), colouring and flavouring agents and fillers.
The compositions of the invention may be used to treat the effects of a hangover or as a prophylaxis for hangover. The invention also encompasses a method of treatment which includes administration of a therapeutically effective amount of a composition according to the invention to a patient. Administration may be before and/or during and/or after consumption of alcohol, to prevent or reduce the effects of a hangover.
Preferably, an effervescent composition containing effective quantities of L-methionine and L-alanine, as well as effervescing agents, and optionally one or more wetting agents, surfactants, colouring agents, flavouring agents or fillers is administered prior to &nd after WO 95/04529 PCT/AU94/00461 -3consumption of alcohol. In a particularly preferred method, a composition according to the invention is administered at least once prior to alcohol consumption and at least twice after alcohol consumption. A suitable delay is allowed between each administration occurring after alcohol consumption, for example, 6 to 10 hours, or overnight.
The invention will now be discussed in relation to tests conducted by the applicant. Two series of tests were conducted, the first with 8 subjects, the second with 3 subjects. The first test shows the effectiveness of the composition of the invention in alleviating or preventing the symptoms of hangover. The second test shows the synergistic effect of administering L-methionine and L-alanine together, rather than separately. These tests are exemplary only, and are not intended to limit the scope of the invention in any way. The tests are illustrated by the accompanying Figures which show as follows: TEST I Figure 1. The mean rating for headache by eight Figure 2.
subjects. The rating was obtained from a visual analog scale where 100 represented a very severe headache, 50 a moderate headache and 25 a slight headache.
The mean rating for nausea by eight subjects.
The rating was obtained from a visual analog scale where 100 represented very severe nausea, moderate nausea and 25 slight nausea.
The mean rating for stomach pain/discomfort by eight subjects. The rating was obtained from a visual analog scale where 100 represented very severe stomach pain/discomfort, 50 moderate stomach pain/discomfort, and 25 slight stomach pain/discomfort.
Global assessment of hangover in the eight subjects. The ratings were obtained from a Figure 3.
Figure 4.
-IILU
WO 95/04529 PCT/AU94/00461 TEST II Figure 5.
Figure 6.
Figure 7.
Figure 8.
-4visual analog scale where 100 represented very severe, 50 moderate and 25 slight. Subject 7 gave a rating of 0 for the global impression of hangover when the amino acids were taken.
The mean rating for headache by 3 subjects.
The rating was obtained as for Figure 1.
The mean rating for nausea by 3 subjects. The rating was obtained as for Figure 2.
The mean rating for stomach pain/discomfort by 3 subjects. The rating was obtained as for Figure 3.
Globol assesment of hangover in the 3 subjects. The ratings were obtained as for Figure 4.
TEST I Because of the difficulty in obtaining an objective method of quantitating "hangover" and because of a perceived psychological component, it was necessary to use a placebo controlled, double blind crossover design for the trial. The trial used six adult males and two adult females as subjects. Subjects were asked to nominate a preferred form of alcohol and a dose which, from previous experience, they would need to imbibe to ensure that they suffered a moderate to severe hangover.
To minimize direct gastric irritation associated with higher alcohol concentrations, the subjects' choice was restricted to drinks having an alcohol content of or less. The alcohol dose is chosen by each subject, as shown in Table i. The alcohol was consumed over a period of three hours, along with a standard meal (pizza as nominated by each subject), which was repeated on each occasion.
-I-
WO 95/04529 PCT/AU94/00461 Table 1. Proposed Alcohol intake Subject Form Dose 1 Rum Coke 350ml Rum 2 Rum Coke 350ml Rum 3 Scotch Soda 350ml Scotch 4 Rum Coke 350ml Rum Rum Coke 350ml Rum 6 Fosters Lager 7 X 700ml Lager 7 Rum Coke 350ml Rum 8 Rum Coke 350ml Rum Prior to each test, subjects were requested to refrain from alcohol for 48 hours prior to each phase of the trial, and until after the final assessement of hangover on each occasion. Subjects were also requested to refrain from taking amino acid supplements in any form for one week prior to the study and for the duration of the study. Subjects were also requested not to make changes in lifestyle during the study (including diet, smoking and exercise).
The trial involved each subject undergoing two tests with one of preparations A and B on each occasion.
Preparation A and B were prepared as follows: Preparation A (Active) L-methionine L-alanine Citric acid anhydrous 2.35g Trucal orange flavour 17-1063 0.3g Sodium lauryl sulphate 1:20 in lactose 0.01g Sodium bicarbonate 2.35g Total 10.01g Preparation B (Placebo) Lactose Citric acid anhydrous 2.35g Trucal orange flavour 17-1063 0.3g Sodium lauryl sulphate 1:20 in lactose 0.01g Sodium bicarbonate 2.35g Total 10.01g WO 95/04529 PCT/AU94/00461 -6- All ingredients were ground to a fine powder with a mortar and pestle before mixing.
PROTOCOL
The protocol for each test was as follows: Day 1 6.30 p.m. Subjects take 10.01 grams of either Preparation A or Preparation B dissolved in 200 ml cold water.
7.00 p.m. Subjects consume a mLal and commence ingestion of alcohol. Alcohol consumption continued up to subject's designated dose over 3 hours.
10.00 p.m. Subjects take 10.01 grams of preparation as before. Subjects were requested not to drink further alcohol and to note fluid ingestion so as to allow for consistency between tests.
Day 2 8.00 a.m. Subjects take 10.01 grams of preparation as before.
The protocol was repeated as above one week later, with each subject taking a different preparation to that taken on the previous occasion. From 6.30 p.m. Day 1 to 6.00 p.m. Day 2, the subjects were required to give subjective evaluations of their physical condition at specified times during the day. Evaluation was by means of a questionnaire.
The questionnaire asked the subjects to record on an analog scale the severity of hangover symptoms, namely: headache, nausea and stomach pain/discomfort. The scales were 10 cm long and were labelled "none", "slight", "moderate", "severe" and severe" at 25 mm intervals.
The subjects were instructed to put a mark on the line at a position best describing their current symptoms. The results were quantified by measuring the distance from the left extremity of the line (labelled "none") to the portion marked on the line by the subject. Thus a rating of severe" would have a quantitive value of 100 where "slight" was 25, "moderate" was 50, and "severe" was LI I e~L~ WO 95/04529 PCT/AU94/00461 -7- The subjects were also asked to rate their "global impression of the hangover" at 6.00 p.m. on Day 2 by means of a similar visual analog scale.
TSULTS
The actual alcohol intake of each subject is shown in Table 2.
Table 2 The actual alcohol intake by subjects on two occasions Alcoholic Beverage Subject Form Volume (ml) Alcohol Dose (ml) 1 Rum Coke 360 133.5 2 Rum Coke 360 133.5 3 Scotch Soda 420 157.5 4 Rum Coke 240 89 Rum Coke 240 89 6 Fosters Lager 4500 234 7 Rum Coke 420 155.8 8 Rum Coke 420 155.8 A subjective evaluation of each symptom was obtained over the course of the trial. The results for each symptom are as follows: Headache The mean results recorded in the questionnaire with respect to headache are summarized in Figure 1. For both preparations, the peak intensity occurred at 8.00 a.m. on Day 2. At all times the mean rating for headache was higher after the subjects took the placebo. The rating for headache declined from the maximum after ingestion of the active ingredients and was back to pre-drinking levels by 6.00 p.m. on Day 2, whereas the level of headache had declined only slightly from the maximum by this time where placebo was used.
The normal parametric statistical tests are not applicable with regard to this symptom because of the many WO 95/04529 PCT/AU94/00461 -8zero values recorded. However, if the incidence of headache regardless of the severity is compared (Table 3) it is obvious that more subjects reported suffering from headache after taking the placebo, particularly at the later time points.
Comparison of the frequencies using the G-statistic shows that the incidence of headache was significantly higher at the last three observation times when the placebo was taken rather than when the active ingredients were taken 0.01<p<0.025.
Table 3 Number of Subjects Reporting some degree of headache (out of eight subjects).
Time Amino Acids Placebo 6.30pm 3 3 10.00pm 3 4 Overnight 4 8.00am 5 7 10.00am 4 6 12 Noon 2 7* 3.00pm 2 7* 6.00pm 2 7* *G test 0.01<p<0.025 Nausea The mean ratings recorded for nausea are shown in Figure 2. The peak for nausea with both preparations occurred at 8.00 a.m. on Day 2. The level of nausea was much higher at all observation points after drinking when the subjects took placebo. For both preparations the level of nausea declined markedly between 8.00 a.m. and 6.00 p.m. on Day 2.
The mean values in this case are misleading since at 8.00 a.m. Day 2 all but two subjects recorded no nausea when amino acids were taken, compared to only one person WO 95/04529 PCT/AU94/00461 -9not recording nausea when the placebo was taken. The results for each subject at 8.00 a.m. Day 2 are shown in Table 4.
A Mann-Whitney non-parametric test on the data for nausea at 8.00 a.m. Day 2 shows that the difference between the products is significant at the 95% level.
The incidence of nausea at the various time points is shown in Table 4. At three of these points there was significantly less nausea after taking the amino acid preparation then after taking the placebo (G test pc0.05).
Table 4 Number of Subjects reporting some degree of Nausea.
Amino Acids Placebo 6.30pm 2 2 10.00pm 1 3 Overnight 3 6 8.00am 2 7* 10.00am 2 7* 12 Noon 3 3.00pm 1 5 6.00pm 2 4 *G test 0.01<p<0.025 G test 0.025<p<0.05 Stomach pain/discomfort The mean ratings for stomach pain/discomfort are shown in Figure 3. As with other symptoms, the severity of stomach pain/discomfort peaked at 8.00 a.m. Day 2.
The rating declined rapidly to pre-drinking levels when subjects took the amino acid preparation, whereas after the placebo, the level of stomach pain/discomfort remained relatively high for the rest of the observation period. Because many of the subjects showed zero values for many time points, the mean values are misleading and parametric statistics cannot be applied. The individual values for 8.00 a.m. Day 2 are shown in Table WO 95/04529 PCT/AU94/00461 Table 5 Subjective evaluation at 8.00am on the morning after alcohol ingestion.
Subjective Rating Headache Nausea Stomach Pain/ Discomfort Subject A.Acid Placebo A.Acid Placebo A.Acid Placebo 1 25 67 0 42 0 2 0 10 0 87 25 3 70 25 75 12 40 4 0 25 0 25 25 22 25 2 10 2 6 0 0 0 0 0 7 5 50 0 50 0 8 20 10 0 10 0 Mean 17.75 26.5 9.625 29.5 11.5 21.875 For explanation of quantitation see protocol.
Another way to view this data is to record the number of subjects showing no signs of a particular symptom at any time point. Results on this basis are presented in Table 6. The number of subjects showing stomach pain/discomfort was higher after placebo than after amino acids at all time points, the difference was statistically significant at four of these points (G test p<0.05).
Table 6 Number of Subjects Reporting some degree of Stomach pain/discomfort.
Time Preparation A.Acid Placebo 6.30 1 2 10.00 2 Overnight 3 7 8.00am 4 8 10.00am 2 4 12 Noon 1 3.00 pm 1 6.00pm 1 4 G test 0.025<p<0.05 G test 0.01<p<0.025 WO 95104529 PCTIAU94/00461 -11- Global Assessment of Hancover by Subiects Seven of the eight subjects rated the hangover as worse when placebo was taken in comparison to when the amino acid preparation was taken. The results for each subject is shown in Figure 4.
Objective Evaluations Two of the eight subjects showed some signs of tremor after taking the amino acids compared with six out of eight showing signs of tremor when the placebo was taken. This difference was statistically significant (0.025<p<0.05).
Four of the eight subjects showed "normal" skin colour after taking the amino acids compared with three out of eight after the placebo.
The appearance of the eyes were similar in each group.
Conclusions From the Test I, it appears that the most outstanding effects of the amino acids were the decrease in nausea and the increase rate of resolution of all symptoms. Although standard parametric statistical tests could not be used due to the large number of observations recording a complete absence of a particular effect, nonparametric tests applied showed a highly significant difference between the two treatment groups. For example, the effect on headache is most apparent about 14 hours after alcohol ingestion. While the amino acids appear to have been only slightly effective in preventing headache, they have been very effective in reducing the severity of the headache. A similar pattern, of effect was seen with stomach pain/discomfort, where in all but one subject, stomach discomfort was virtually gone by 10.00 a.m. on Day 2 when the amino acids were taken in contrast to the placebo where five subjects were still suffering significant stomach discomfort at this time.
WO 95/04529 PCT/AU94/00461 -12- TEST II
SUBJECTS
This trial was performed with three of the subjects that participated in Test I in which the preparation containing a combination of L-alanine with L-methionine was evaluated. The subjects were 2 adult males and 1 adult female.
DOSEIORMS
Subjects took either 2.5g of L-alanine in powder form or 2.5g of L-methionine in powder form.
Alcohol Dose and Form Subjects used the same dose as in Test I.
Subiect Form Alcohol Dose 2 Rum Coke 133.5 ml 5 Rum Coke 89.0 ml 8 Rum Coke 155.8 ml
PROTOCOL
Subjects were requested to refrain from alcohol for 48 hours prior to the study and until after the completion of the study.
Subjects were requested to refrain from taking amino acid supplements .in any form for one week prior to the study and for the duration of the study.
The subjects consumed the dose of alcohol with a meal over a period of approximately three hours.
6.30 pm Subject takes a level spoonful (approximately of either L-alanine or L-methionine with 200ml of water. Subjects fill in quesionaire.
7.00 pm Subjects eat and start consuming alcohol.
10.00 pm Subjects take a level spoonful of either Lalanine or L-methionine, as before Subjects complete alcohol ingestion. Subjects fill in questionnaire.
Next day 8.00 am Subjects take a spoonful of either L-alanine or L-methionine, as before. Subjects fill in questionnaire.
uLI ;I I WO 95/04529 PCT/AU94/00461 -13- 9.00 am Subjects expected to report to work to try to carry out normal duties.
10.00 am Subjects fill in questionnaire.
12.00 pm Subjects fill in questionnaire.
3.00 pm Subjects fill in questionnaire.
6.00 pm Subjects fill in questionnaire.
The protocol was completed for both L-methionine and L-alanine with each subject.
EVALUATION
The evaluation was based on questionnaires.
The questionnaire was filled out at times indicated in the protocol. The subjects were asked to record on an analog scale the severity of headache, nausea and stomach pain/discomfort as in Test I.
The subjects were also asked to rate their "global Impression of the Hangover" at 6.00 pm on the day following the alcohol ingestion.
RESULTS
The results from this study together with the results obtained for the Placebo and the combination of L-alanine and L-methionine for these sub3ects in Test I are shown in Figures 5 to 8.
The rating given by the subjects for headache is shown in Figure 5. The combination of the amino acids was the only treatment to give a lower intensity of headache than Placebo.
The rating given by the subjects for nausea are shown in Figure 6. The combination is the only treatment that gave a lower intensity for nausea than Placebo.
The ratings given by the subjects for stomach pain/discomfort are shown in Figure 7. The combination is the only treatment that gave a lower rating for stomach pain/discomfort than Placebo.
The overall rating of hangover is shown in Figure 8. The mean ratings show that there is little difference between Placebo and either of the amino acids
I
WO 95/04529 PCT/AU94/00461 -14when given singly. The rating when the combination was given was significantly lower than any of the other treatments.
CONCLUSIONS
In Test II, the amino acids L-alanine and Lmethionine were found to have little beneficial effect when taken separately for "hangover". This is in contrast to when the combination is taken together.
It should be realized that various modifications and/or additions may be introduced to the compositions and nethod of treatment described herein without departing from the spirit or ambit of the invention.
Claims (10)
1. A composition including prophylactically or therapeutically effective amounts of L-methionine and L-alanine, or pharmaceutically acceptable salts thereof as active ingredients, when used to reduce the symptoms of hangover in a person in need thereof.
2. A composition according to claim 1 wherein the weight ratio of L- methionine to L-alanine ranges from 1:2 to 2:1.
3. A composition according to claim 1 wherein the composition is adapted for solution in water.
4. A composition according to claim 1 wherein the composition includes an Seffervescing agent, and/or a surfactant, and/or colouring and flavouring agents S 15 and/or a pharmaceutically acceptable filler. 0 *0
5. A composition according to claim 4 wherein the effervescing agent includes a mixture of citric acid anhydrous and sodium bicarbonate. 20
6. A composition according to claim 4 wherein the surfactant includes sodium lauryl sulphate.
7. A composition according to claim 1 wherein the composition contains at least 1g of each active ingredient.
8. A composition according to claim 1, comprising by weight: g L-methionine g L-alanine 2.35g citric acid anhydrous 0.3g Trucal orange flavour 17-1063 F. 0.01g Sodium lauryl sulphate in 1:20 lactose JJ C:\WINWORDU\ACKIENODELTE73779N94.DOC II ~bl 16
9. A composition according to claim 1 wherein the composition is administered before and/or during and/or after consumption of alcohol.
10. A composition according to claim 1 wherein the composition is administered once before consumption of alcohol, and twice after consumption of alcohol, wherein the administrations after consumption of alcohol are separated by 6 to 10 hours. DATED 13 December, 1996 PHILLIPS ORMONDE FITZPATRICK 15 Attorneys for: MUSASHI PTY LTD a o o 44*4 iJ C:\WINWORDUACKIENODELETh73779N94-DOC
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU73779/94A AU680674B2 (en) | 1993-08-10 | 1994-08-10 | Composition for treatment of hangovers |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPM045093 | 1993-08-10 | ||
| AUPM0450 | 1993-08-10 | ||
| PCT/AU1994/000461 WO1995004529A1 (en) | 1993-08-10 | 1994-08-10 | Composition for treatment of hangovers |
| AU73779/94A AU680674B2 (en) | 1993-08-10 | 1994-08-10 | Composition for treatment of hangovers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU7377994A AU7377994A (en) | 1995-02-28 |
| AU680674B2 true AU680674B2 (en) | 1997-08-07 |
Family
ID=25637405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU73779/94A Ceased AU680674B2 (en) | 1993-08-10 | 1994-08-10 | Composition for treatment of hangovers |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU680674B2 (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4357343A (en) * | 1981-06-26 | 1982-11-02 | Baxter Travenol Laboratories, Inc. | Nutritional composition for management of renal failure |
| DE3414491A1 (en) * | 1984-04-17 | 1985-10-24 | Hans Dr. 8202 Bad Aibling Dietl | L-Amino acid mixtures for parenteral and oral use for kidney disorders |
| US4792549A (en) * | 1986-01-13 | 1988-12-20 | Morinaga Milk Industry Co., Ltd. | Composition of amino acids |
-
1994
- 1994-08-10 AU AU73779/94A patent/AU680674B2/en not_active Ceased
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4357343A (en) * | 1981-06-26 | 1982-11-02 | Baxter Travenol Laboratories, Inc. | Nutritional composition for management of renal failure |
| DE3414491A1 (en) * | 1984-04-17 | 1985-10-24 | Hans Dr. 8202 Bad Aibling Dietl | L-Amino acid mixtures for parenteral and oral use for kidney disorders |
| US4792549A (en) * | 1986-01-13 | 1988-12-20 | Morinaga Milk Industry Co., Ltd. | Composition of amino acids |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7377994A (en) | 1995-02-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ly et al. | The potential of dental-protective chewing gum in oral health interventions | |
| König | Role of fluoride toothpastes in a caries-preventive strategy | |
| CA1326212C (en) | Salivary stimulant | |
| KR101553719B1 (en) | Liquid compositions of calcium acetate | |
| US5240961A (en) | Method of treating reduced insulin-like growth factor and bone loss associated with aging | |
| US8703209B2 (en) | Composition and method for modulating hydrogen ion physiology | |
| US5712309A (en) | Composition for treatment of hangovers | |
| EP0859619A1 (en) | Multiple vitamin supplement composition | |
| US20030185876A1 (en) | Nutrient formulations | |
| DE69906651T2 (en) | Slow release compositions containing a zinc compound and vitamin C derivatives | |
| US7867521B2 (en) | Aspartame and citrate flavored phosphate salt laxative | |
| DE69928027T2 (en) | Pharmaceutical composition | |
| HU228989B1 (en) | Compositions and methods for increasing the concentration and/or motility of spermatozoa in humans | |
| US5011688A (en) | Liquid composition for the relief of premenstrual and menstrual discomforts | |
| JPH06506682A (en) | Oral pharmaceutical composition for treating upper gastrointestinal tract symptoms | |
| EP0449787A2 (en) | Pharmaceutical, dietetic or veterinary compositions with eumetabolic activity | |
| JP3055948B2 (en) | Agent for improving skin pruritus associated with renal failure | |
| AU680674B2 (en) | Composition for treatment of hangovers | |
| JP2016210758A (en) | Oral care composition, tablets, granular drugs | |
| DE19502789A1 (en) | Medicament contg. analgesic, antacid, and/or vitamin etc. | |
| US20040082667A1 (en) | Hangover treatment | |
| JPH07196523A (en) | Internal liquid preparation containing quercetin glycoside | |
| EP0719148A1 (en) | Oral water soluble pharmaceutical compositions containing estrone derivative and calcium salt | |
| Wester et al. | Magnesium and hypertension. | |
| US5153005A (en) | Composition and method for preventing fluorosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired | ||
| NA | Applications received for extensions of time, section 223 |
Free format text: AN APPLICATION TO EXTEND THE TIME FROM 19990810 TO 20001210 IN WHICH TO PAY A RENEWAL FEE HAS BEEN LODGED |
|
| NB | Applications allowed - extensions of time section 223(2) |
Free format text: THE TIME IN WHICH TO PAY A RENEWAL FEE HAS BEEN EXTENDED TO 20001210 |