JPH05971A - Medicinal composition - Google Patents

Abstract

PURPOSE: To obtain a medicine composition for oral administration, effective for reducing influence of drinking too much alcohol, containing an antihistamine. CONSTITUTION: This composition comprises an antihistamine, especially 20-100mg of diphenhydramine hydrochloride as an active ingredient. The composition is suitable for oral administration form such as capsule, tablet or syrup and alleviates the symptom called hangover after drinking too much alcohol such as headache, feel like vomiting, tremble and ache of hand and foot. Diphenhydramine, an ethanolamine such as doxylamine, an ethylenediamine such as pyrilamine, an alkylamine such as chlorophenylamine, a piperazine such as chlorocyclizine and a phenothiazine such as promethazine may be used as the antihistamine.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to pharmaceutical compositions.

[0002]

BACKGROUND OF THE INVENTION Overdose of beverages containing ethyl alcohol is known to cause many adverse short-term effects. Collectively they are usually referred to as "hangovers" and are quite different from the long-term biochemical and pathomorphological changes known to accompany alcohol drinking. The usual symptoms of a hangover are; headache, nausea, shivering (trembling), or depression, and muscle pain the next day after overdose-a "hangover" syndrome. Insomnia will occur after a few hours of sleep after ingestion.

Despite not being a wise practice, for centuries the regular overdose of beverages containing ethanol is part of social life, and perhaps even in many civilizations even a symbol of social status. It has been accepted. Such social drinking and acceptance of ethanol is at least 10 times older than the use of tobacco in Western culture. This habit is an important part of lifestyle, at least in some classes of society, so it would be very impossible to eliminate them in a few generations.

Excessive eating and drinking of parties and dinner causes discomfort in various functions of the body. For example, if you drink too much alcohol, your liver will work hard and alcohol will
Have the effect of having to disassemble the module. Commercially, there are compositions designed to assist the metabolic functions of the liver under these circumstances. Such preparations include glucuronolactone, glucuronamine,
There are ascorbic acid and caffeine.

Other therapeutically useful preparations that are effective against nausea or overdose are essentially products containing large numbers of vitamins.

[0006]

It has been unexpectedly discovered that antihistamines are effective in reducing the effects of alcohol overdose, forming the basis of the present invention.

Thus, according to one of the aspects of the present invention,
To provide the use of antihistamines to reduce the effects of alcohol overdose.

Further in accordance with the invention, it is suitable for oral administration,
A composition comprising an effective amount of antihistamine to reduce the effects of alcohol overdose is provided.

Further according to the present invention, there is provided an antihistamine for use in the method for producing the pharmaceutical composition of the above-mentioned form.

[0010]

Examples of suitable antihistamines are diphenhydramine, ethanolamines such as doxylamine, ethylenediamines such as pyrylamine, alkylamines such as chlorophenylamine, piperazine such as chlorocyclidine and It is a phenothiazine such as promethazine.

The antihistamine can be provided in the form of a base or in the form of a pharmaceutically acceptable salt. Suitable salts are hydrochlorides, phosphates, succinates, maleates, theoclates, lactates, citrates and tannates.

The preferred antihistamine is diphenhydramine hydrochloride.

Antihistamines can be the active ingredient in pharmaceutical compositions. Examples of suitable pharmaceutical forms are liquids such as capsules, tablets, syrups. Antihistamines are typically
It is present in the composition in an amount of 20 to 100 mg.

The pharmaceutical composition is administered to a person after the person has taken the alcohol. If the composition is administered prior to alcohol intake, it will have a stimulating effect. Suitable pharmaceutical compositions of the present invention are shown below.

[0015]

Example 1 Capsule Diphenylhydramine Hydrochloride 25 mg Paracetamol 250 mg L-Carnitine 300 mg Excipient Quarter Tablet Diphenylhydramine Hydrochloride 30 mg Paracetamol 350 mg Tablet Excipient Up to 550 mg Tablet Promethazine Hydrochloride 25 mg Paracetamol 350 mg tablet excipient Up to 550 mg tablets of the above diphenhydramine hydrochloride were evaluated in a double blind cross-validation method using placebo. Seventeen people participated in this assay and were given two tablets after taking the alcohol. This study finally showed that the effects after alcohol overdose were reduced.

[0016]

Example 2 From empirical observations by a large number of individuals, aftereffects of overdose, some of which can be prevented or reduced by drinking 50 or 60 mg of diphenhydramine before bedtime after overdose, were reported here. Led the study.

This study is a double-blind, cross-clinical study in which symptoms are assessed by participant scoring and in-built hard-data for ethanol blood level assessment. Also used.

Pharmaceutical Considerations Diphenhydramine is well known as a histamine H1-receptor antagonist, but probably antimuscarinic M
_It also has properties such as ₂ -receptor, alpha ₁ -adrenergic and, at high concentrations, dopamine D ₁ -antagonist and anti-serotonergic. in addition,
This compound also has the potential for local anesthesia-like properties. All these properties are associated with the prevention of hangover syndrome.

Statistical Analysis and Results Statistical analysis procedures, methods and results are shown below.

Conclusions This double-blind study was conducted on 25 of 27 people. Two
The reason for the dropout is unknown. Of the 25, 24 experienced headaches as a significant hangover syndrome, while none or only minor other symptoms were reported (in terms of n-value) despite a clear questionnaire.

There were no significant changes in blood alcohol levels before and after treatment, which may conclude that there was probably no significant difference in the extent of drunkenness in the individual for this two aspects. Will.

Overall, however, the symptoms can be highly significantly reduced by pretreatment with diphenhydramine (p
For personal symptoms, headache (p = 0,0016), nausea (p = 0,0781), insomnia (p = 0,0795) and shivering (p = 0,093).
8) has decreased. Depression and limb pain were not significantly affected.

Principles of Biological Statistics Initially: The purpose of this study was to test whether a certain number of people would benefit from the new anti-hangover drugs.

In both cases, 25 men and women were entertained at 14-day intervals and consumed as much alcohol as possible. In the first case, half were given anti-hangover drugs and the other half were given placebo. In the second case each person is given in reverse,
As a result, each person became his own control.

Blood alcohol levels were measured in each case for each of the two cases. Variables such as weight, height, and gender were observed. These values for weight, height and age were placed in separate categories, indicating non-analytical, statistical values.

In addition, these people were asked to indicate on their form what symptoms they would normally experience after the party. The next day, they were asked to write down the degree of symptoms they experienced, on a scale of 1 to 10.
The value indicates that 1 is no symptom and 10 is a very severe symptom. There were also weights associated with the importance of the condition.

[0027]                                 table Symptom weighted name                                               Drug placebo Headache 10 AA1 (AB1) BA1 (BB1) Nausea 5 AA2 (AB2) BA2 (BB2) Shivering 5 AA3 (AB3) BA3 (BB3) Pain in limbs 2 AA4 (AB4) BA4 (BB4) Depression 2 AA5 (AB5) BA5 (BB5) Insomnia: Initial time 2 AA6 (AB6) BA6 (BB6) The name in parentheses is the variable given to the particular condition present.
Is a number.

Statistical Analysis Weight Index (IBM) is determined as weight (Kg) / height (meter). Given that the two measures are classified, the calculation was accomplished by obtaining the median classification for each person.

In addition, the general percentage is calculated for each person when active and placebo are used. The calculation is carried out as follows: (Note: weighted value is 0 if no symptoms are noted) SUMA = total weighted value of symptoms shown when active drug is used.

[0030] SUMB = total weighted value of symptoms shown when placebo was used.

[0031] The value of PERSA = TOTA / SUMA PERSB = TOTB / SUMB PERSA and PERSB will vary between 0,1 and 1,0 due to its last effect if the value reaches 0,1.

[0032] Wilcoxon ¹ (Wilcoxon ¹⁾ double-blind is,
Made using placebo for comparison. The Mann-Whitney U-test was used to determine whether gender and age had an effect. BM
Correlation-coefficients were used to determine if there was a linear association between I and certain variables.

Deviations from the norm were neglected because the mean was calculated for interpretation and the data was anomalous divided.

Results: We compared the effects of various symptoms between drug and placebo on those who describe the symptoms they experienced. The results are summarized in Table I. (See Printout 1) Table I Wilcoxon ¹ Mean and p-values based on double-blinds for drug effects compared to symptoms and placebo Mean symptoms n Active drug Placebo p-value Headache 24 2,5833 5,2500 0 , 0016 Nausea 14 1,3571 2,2857 0,0781 Shivering 20 2,0500 2,9500 0,0938 Pain in limbs 11 2,5455 3,0909 0,6563 Depression 10 1,2000 1,5000 0,7500 Insomnia 17 2,2353 3,2941 0,0795 All factors (PERSA V PERSB) 25 0,4171 0,7183 0,0061 Blood alcohol 25 0,1136 0,1256 0,3858 Table I Blood alcohol It is clear that there was no significant difference between taking the drug and placebo at the le level. Regarding the next morning's headache, it seems that taking the drug at night was less acute than taking placebo at night. All factors were also taken into account as the general health of the people.

There were 20 men and 5 women. There was no difference in sex compared (see printout 2A) for any of the above symptoms.

Regarding the age, that is, when comparing the symptoms of a person under 39 years old, with respect to a person over 40 years old, it is found that only the average value of blood alcohol is different (average 39 = 0,085).
6; gem 40 = 0,1320; p = 0,0229). (Printout 2B p20
reference).

[0037] Comparing alcohol drinkers with occasional drinkers, the drinkers are more likely to fall asleep than the occasional drinkers.
(3,7143 vs. 1,1667; p = 0,0309) (Printout 2C p27) and more residual effects after active substance intake were higher in habitual drinkers (0,6097 vs. 0,2887; p = 0. , 0455) (Print out
2C p32). There was no linear relationship between BMI and alcohol levels, but a slight positive correlation was obtained between active drug and placebo with respect to alcohol levels in individuals prior to taking them (r = 0,438; p = 0,028) (see printout 3).

Reference 1. Wilcoxin Sign Rank Test (WILCOXON SIG
NED RANK TEST) Siegel S (1956) Non-parametric statistics on behavioral science, McGraw-Hillnew York. 75-83 pages. (Siegel S (1
956) Nonparametric statistics for the behavioral s
cience, McGraw Hill NY. Page 75-83) 2. MANN-WHITNEY U TEST Siger S (1956) Non-parameter statistics on behavioral science, McGraw-Hill New York -Ku. Pages 68-75. (Siegel S
(1956) Nonparametric statistics for the behavioral
science, McGraw Hill NY. Page 68-75)

Claims (8)

[Claims] 1. A composition comprising an antihistamine in an amount effective to reduce the effects of alcohol overdose. 2. The composition according to claim 1, wherein the composition is in a form suitable for oral administration. 3. A composition according to claim 1 or 2 selected from capsules, tablets and solutions. 4. The composition according to claim 1, wherein the antihistamine is present in an amount of 20-100 mg. 5. The antihistamine is ethanolamine,
A composition according to any of claims 1 to 4 selected from ethylenediamine, alkylamines, piperazine and phenothiazine. 6. The antihistamine is selected from diphenhydramine, doxylamine, pyrylamine, chloropheniramine and promethazine.
The composition according to any one of 1. 7. The composition according to claim 1, wherein the antihistamine is in the form of a pharmaceutically acceptable salt. 8. The composition according to claim 1, wherein the antihistamine is diphenhydramine hydrochloride.