GB2198041A - Inhibiting alcohol addiction - Google Patents
Inhibiting alcohol addiction Download PDFInfo
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- GB2198041A GB2198041A GB08706977A GB8706977A GB2198041A GB 2198041 A GB2198041 A GB 2198041A GB 08706977 A GB08706977 A GB 08706977A GB 8706977 A GB8706977 A GB 8706977A GB 2198041 A GB2198041 A GB 2198041A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
- C12G3/00—Preparation of other alcoholic beverages
- C12G3/04—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
Abstract
Compositions for inhibiting alcohol addiction contain: leukoanthocyans, catechins, flavanols, lignin, reducing sugars, pectin, free aminoacids, organic acids, sterols, methylsterols, dimethysterols, lignanes, lignane glycosides, phenolic acids, phenol aldehydes and alkylferulates. Alcoholic beverages containing these compositions are also disclosed.
Description
comPosition Inhibitinq Patholoqical Addiction to Alcohol
Field of the Invention
The present invention relates to compositions for inhibiting the development of a pathological addiction to alcohol, and to processes for their manufacture.
Background of the Invention
Known in the art is an alcoholic bitter liqueur comprising the following ingredients, kg/l,000 decalitres:
Aralia root 2. S Eleutherococcus extract 20
Schizandra (fresh berry) 345
Sugar 200
Natural honey 50
Tint 25
Aqueo-alcoholic liquid the balance.
(See "Pormulations of Liqueur-Vodka Products and
Vodkas", Legkaya i Pistschevaya Promyshlennost" (Light and Food Industry) Publishing House, Moscow, 1981, p.188).
Also known in the art is an alcoholic bitter liqueur including the following ingredients, kg/1,000 decalitres:
Eleutherococcus extract 200
Schizandra (fresh berry) 92
Schizandra (seeds) 0.6
Natural honey 50
Tint 30
Aqueo-alcoholic liquid the balance.
(See "Formulations of liqueur-Vodka Products and Vodkas", Light and Food Industry Publishing House,
Moscow, 1981, p.206.)
The prior art alcoholic liqueurs are produced by way of blending the starting components, a successive introduction, into the resulting blend, of an aqueoalcoholic liquid, settling of the resulting mixture and filtration thereof.
As it is seen from the above-specified formulations, the latter contain a biologically active extract of
Eleutherococcus which lowers the toxic effect of ethanol 9 in a living organism.
However, low taste properaties of the prior art beverages caused by a limited content of aromatic compounds, as well as a "pharmaceutical" aftertaste due to the presence of Eleutherococcus extract, high costs of the starting ingredient - Eleutherococcus extract and limited availability of this plant do not enable a wide scale of consumption of these prior art beverages.
The present invention resides in the provision of a composition inhibiting the development of a pathological addiction to alcohol which, according to the present invention, comprises the following ingredients, mg/g:
leukoanthocyanes 219-270
catechins 153-187
flavanols 81-99
lignin 68-83
reducing sugars 216-264
pectin 18-22
free amino acids 27-33
organic acids 36-44
sterols 4.5-5.5
methylsterols 1.35-1.65 dimethylsterols 1.98-2.42
lignans 13.5-16.5 lignan glycosides 9-11
phenolic acids 13.5-16.5
phenolic aldehydes 4.5-5,5 alkylferulates 4,5-5.5 The composition according to the present invention advantageously comprises a combination of compounds occurring in nature.The composition has a pronounced capability of affecting processes of ethanol metabolism without switching to unfavourable routes of the organism's utilization of ethanol; as a result, the process of formation of a physical dependence on alcohol is delayed, the level of its consumption is lowered and certain alcoholic behaviour excesses disappear.
Furthermore, the composition according to the present invention is not toxic and is safe upon prolonged consumption; it has positive organoleptic characteristics and can be useful as a food additive to alcoholic and alcohol-free beverages.
In a preferred aspect, the present invention resides in that an alcoholic beverage comprising sugar, citric acid, a tint and an aqueous-alcoholic liquid, according to the present invention also incorporates fruit alcohol and a composition of substances inhibiting the development of a pathological addiction to alcohol containing, mg/g: leukoanthocyanes - 219-270, catechins - 153-187, flavanols - 81-99, lignin - 68-83, reducing sugars - 216-264, pectin - 18-22, free amino acids -27-33, organic acids - 36-44, sterols - 4,5-5.5, methylsterols - 1.35-1.65, dimethylsterols - 1.98-2.42, lignans - 13.5-16.5, lignan glycosides - 9-11, phenolic acids - 13.5-16.5, phenol aldehydes - 4.5-515, alkylferulates - 4.5-5.5, the ingredients being present in the following proportions, kg per 1,000 decalitre of the beverage: the above-specified composition 473-493 fruit alcohol 40 4,950-5,050 sugar 95-105 citric acid 1.8-2.2 tint 28-32 aqueous-alcoholic liquid the balance.
The alcoholic beverage according to the present invention is capable of inhibiting a pathological addiction to alcohol and has high organoleptic properties - the tasting test of the beverage is not less than 9.1 points.
This alcoholic beverage may be produced by a process comprising blending of sugar, citric acid and a tint, followed by the addition, to the resulting blend, of an aqueo-alcoholic liquid, settling and filtration, wherein according to the present invention blended are 473-493 kg of a composition inhibiting a pathologic addiction to alcohol, 4,950-5,050 kg of a 40 fruit alcohol, 95-105 kg of sugar, 1.8-2.2 kg of citric acid and 28-32 kg of tint; to the resulting blend the aqueous-alcoholic liquid is added in the amount required for the preparation of 1,000 decalitre of the beverage; prior to settling and filtration the final blend is subjected to a triple successive thermal treatment for 5-8 hours at a temperature of 70-80"C and to cooling to attain a temperature within the range of from 0 to -10 C.
Other subjects and advantages of the present invention will now be more fully apparent from the following detailed description of the alcoholic beverage and the process for producing same according to the present invention.
The beverage according to the present invention contains, kg per 1,000 decalitre of the beverage:
Composition inhibiting a pathological addiction to alcohol 473-493 400 fruit alcohol such as pear alcohol, apple alcohol, plum alcohol, tangerine alcohol 4,950-5,050 sugar 95-105 citric acid 1.8-2.2 tint 28-32 an aqueo-alcoholic liquid the balance (comprising a mixture of water and ethanol in a desired ratio)
The desired ratio of ethanol and water in this mixture depends on the final strength of the produced beverage.
When the alcoholic beverage of the present invention is consumed, the process of the formation of a physical dependence on ethanol in the organism is inhibited.
Furthermore, drinking of this beverage is not accompanied by such negative effects as a "hang-over" syndrome.
The tasting test value of the above alcoholic beverage according to the present invention is not less than 9.1 points. An improvement in organoleptic properties is attained due to an increased content of aromatic substances, in particular esters of derivatives of aromatic acids and higher alcohols, as well as due to interaction of aldehydes ketones, acetals and alkylferulates being present in the beverage composition.
An alcoholic beverage according to the present invention is produced in the following manner. There are blended: a composition inhibiting the development of a pathological addiction to alcohol, a fruit alcohol, sugar, citric acid, a tint, whereafter the resulting blend is added with an aqueo-ethanolic liquid in an amount necessary to obtain the beverage of 40% strength. Then the resulting blend is subjected to a successive heat treatment for three times at a temperature of 70-80"C for a period of 5-8 hours.
Thereafter, the blend is cooled for a period sufficient to acquire a temperature within the range of from 0 to 1000. Then the thus-produced beverage is filtered, allowed to stand for 10 days at a temperature varied within the range of from 10 to 45"C and again filtered.
Production Example 1
There are blended 483 kg of a composition containing, mg/g: leukoanthocyans - 245.0, catechins 180.0, flavanols - 90.0, lignin - 75.0, reducing sugars - 261.7, pectin - 20.0, free amino acids - 30.6, organic acids - 39.0, sterols - 5.0, methylsterols - 1.5, dimethylsterols - 2.2, lignans - 15.0, lignan glycosides - 10.0, phenolic acids - 15.0, phenol aldehydes - 5.0, alkylferulates - 5.0, 40 pear alcohol - 4,990 kg, sugar - 105 kg, citric acid - 2.2 kg, tint - 32 kg and an aqueo-ethanolic liquid in an amount required to obtain a blend following heat treatment at the temperature of 750C for 6 hours. Thereafter the blend is cooled to a temperature of 0 to 2"C. Then the beverage is filtered, settled for 10 days at a temperature within the range of from 10 to 15"C.
The final product is filtered while being bottled.
Production Example 2
A beverage is produced by blending 473 kg of a composition containing the following ingredients in the amounts specified hereinbelow, mg/g: leukoanthocyans 219, catechins - 153, flavanols - 81, lignin - 68, reducing sugars - 345.17, pectin - 16, free amino acids - 27, organic acids - 36, sterols - 4.5, methylsterols 1.35, dimethylsterols - 1.98, lignans - 13.5, lignan glycosides - 9, phenolic acids - 13.5, phenol aldehydes - 4.5, alkylferulates - 4.5.
It also contains, as indicated in Example 1, 4,950 kg of a 400C plum alcohol, 95 kg of sugar, 1.8 kg of citric acid, 28 kg of a tint and an aqueo-ethanolic liquid in an amount sufficient to obtain a blend with the strength of 40 vol%. Thereafter the blend is subjected to a triple successive heat treatment for 5 hours at the temperature of 80"C. Then the blend is cooled for a period of time sufficient to acquire a temperature of 0 to 10C. Then the beverage is filtered, allowed to stand for 10 days at a temperature of 20 to 220C.
The final product is again filtered when being bottled.
Production Example 3
There are blended 493 kg of a composition containing the following ingredients in the amounts specified hereinbelow, mg/g: leukoanthocyans - 270, catechins 187, flavanols - 99, lignin - 83, reducing sugars 197.5, pectin - 22, free amino acids - 33, organic acids - 44, sterols - 5.5, methylsterols - 1.65, dimethylsterols - 2.42, lignans - 16.5, lignan glycosides - 11, phenolic acids - 16.5, phenol aldehydes - 5.5, alkylferulates - 5.5, a 400 tangerine alcohol 5,050 kg, sugar - 105 kg, citric acid - 2.2 kg, tint 32 kg, an aqueo-alcoholic liquid in an amount sufficient to obtain a blend of a 40 vol.% strength. Thereafter the blend is subjected to a triple successive heat treatment for 5 hours at the temperature of 800C.Then the blend is cooled for a period of time sufficient for it to acquire a temperature of 8-10 C. Then the beverage is filtered, allowed to stand for 10 days at a temperature of from 40 to 450C.
The final product is again filtered when being bottled.
Further objects and advantages of the present invention will now become more fully apparent from the following detailed description of a composition inhibiting the development of a pathological addiction to alcohol with reference to examples illustrating its particular embodiments.
The composition according to the present invention preferably contains, as leukoanthocyanes, leukodolphinidine, leukocyanidine and leukopelargonidine. As catechins it contains (-)epigallocatechin, (+)gallocatechin, (-)epicatechin, (+) catechin and (-)epicatechingallate. As flavanols the composition according to the present invention contains kaempferol-3-monoglucoside, quercetin-3-monoglucoside, myricetin-3-monoglucoside and astragalin. As sugars it contains D-glucose, D-fructose, saccharose, raffinose, arabinose, xylose. As free amino acids the composition according to the present invention contains lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, cystine, valine, methionine, isoleucine, leucine, tyrosine and phenylalanine.As organic acids it contains tartaric acid, malic acid, citric acid, ascorbic acid, a-ketoglutaric acid, fumaric acid, galacturonic acid, glyceric acid, glycolic acid, glycouronic acid, oxalic acid, succinic acid, shikimic acid. As sterols the composition according to the present invention contains 8-cetosterol, stigmasterol, kaempesterol. As methylsterols it contains obtusifoliol, citrostadienol. As dimethylsterols it incorporates a-amyrin, ss-amyrin, lupeol, taraksterol, taraxasterol, germanicol. As lignans the composition according to the present invention contains oxymatairesinol, matairesinol, pinoresionol, liovyl, isolariciresinol and olivyl. As lignan glycosides it contains querinol arabinoside and querinol xyloside. As phenolic acids it contains paraoxybenzoic acid, protocatechinic acid, gallic acid, vanillic acid and syringic phenolic acids. As phenolic aldehydes the composition according to the present invention contains vanilline, syringic aldehyde, sinapic aldehyde and coniferyl aldehyde. As alkylferulates it contains alkyl esters of ferulic acid with the alcohol moiety being represented by octadecanol, eicosanol, docosanol, tetracosanol, hexacosanol.
The above-mentioned composition of the herein-before-listed ingredients can also be obtained in the form of naturally-occurring complexes of biologically active substances of the vegetable origin.
The above-mentioned composition of the hereinbefore-listed ingredients is soluble in water, ethanol and aqueous-alcoholic solutions.
The composition according to the present invention has a low toxicity: LD50 is 36.5 ml per 1.000 g of body-mass of a rat.
We have carried out pharmacological studies of the effect of the composition according to the present invention on processes of ethanol consumption and on the formation of a physical dependence on animals and human beings.
Under conditions of a chronic experiment (15 weeks) on mature male rats of Wistar line the level of ethanol consumption was studied under the conditions of free choice between water and a 15% ethanol. Prior thereto the rats were tested for resistance to ethanol by the "side posture" procedure upon an intraperitoneal administration of a 25% ethanol at the rate of 4.5 g/kg of the body mass of the animals. In the experiment rats with similar characteristics of a high tolerance towards ethanol were used. Later on the animal were placed into cases with calibrated drinking bowls under conditions of free choice between a 15% ethanol and water, and the daily consumption of the liquids was recorded.
The control group was composed of animals (12 rats) that consumed a 15% ethanol.
In the test group (12 rats) the composition according to the present invention was added to a 15% ethanol in the drinking bowl in the amount of 1 ml per 50 ml of 15% ethanol. After 13 weeks of active alcoholization the animals were deprived of the access to alcohol for 10 days (deprivation period) and then the amount of consumed solutions was recorded again. The experimental data are shown in Table 1.
In the group of control animals the deprivation period proceeded with withdrawal phenomena which manifested in a changed behaviour of the animals, signs of tremor were recorded, a moderate dishevelling of hair was noted. At the same time, in the control group no withdrawal symptons were observed.
The character of consumption of a 15t ethanol under free choice conditions in the control group was different from that of consumption of a 15% ethanol with the composition according to the present invention in the test group. Beginning from the 8th weeks a clearly pronounced trend towards reduction of ethanol consumption in combination with the composition according to the present invention was observed and after deprivation this difference was exceeding 100%.
An important indicator of a formed physical dependence on ethanol in the control group was an increased rate of ethanol consumption after a 10-days' deprivation by 12%. In the test group the consumption of ethanol in combination with the composition according to the present invention after deprivation remained at the same level.
TABLE 1
Effect of the composition according to the present invention on the amount of consumed 15% ethanol on a daily basis (in ml/kg of 1 animal's bodyweight) under free choice conditions Table 1
Statis tic pa- Time of consumption (in weeks) rameter 1 2 3 4 5 6 7 8 9 10 11 12 13 15 1. Amount of M# 28.9 20.1 22.5 26.6 28.3 25.6 27.5 26.8 24.0 28.2 29.7 29.4 24.7 Depri- 29.4 vation Consumed 15% m 1.86 1.18 2.29 2.05 1.8 1.97 2.32 1.33 2.06 2.25 1.76 3.44 1.29 10 3.12 ethanol (eon- days trol group) Depri2. Amount of M# 33.8 32.2 37.0 34.0 25.9 26.6 29.8 15.3 18.9 22.0 22.0 20.0 13.0 va- 13.0 consumed 15% m 3.88 4.09 2.93 3.11 2.53 2.26 1.3 1.49 1.36 2.17 1.66 2.42 2.12 tion 2.41 10 ethanol with P 0.05 0.05 0.01 0.2 0.1 - - 0.01 0.0001 0.2 0.1 0.05 addition of 0.001 days 0.00 the composi tion of this invention (1 ml per 50 ml of et hanol) time of consumpticn (in weeks) Addition, to a 15% ethanol, of the composition according to the present invention under conditions of a long-time forced alcoholization (38 months) with the absence of water in the food diet has resulted in a substantial redistribution of animals in groups of alcohol consumption (Table 2).
TABLE 2
Effect of the composition according to the present invention on distribution of rats according to the rate of consumption of a 15% ethanol (in per cent) (forced alcoholization),
Alcoholization tie Groups of animals 3 months 6 months 8 months Low-drinking (20-60 ml per 1,000 g of the bodymass) 26/45 73/76 67/79 Me dium-drinking (60-80 ml per 1 OOOg of the bodymass) 31/12 22/21 21/15 Heavily-drinking above 80 ml per 1,000g of the bodymass) 43/13 5/3 12/6 t) Note: In the numerator - consumption of a 15% ethanol, in the denominator - consumption of a 15% ethanol with the addition of a composition according to the present invention.
The conditions of this experiment contemplated an individual control of consumption of test solutions in groups of animals; among the rats administered with alcohol incorporating the composition according to the present invention the number of heavily-drinking animals was certainly smaller.
To avoid possible organoleptic effect of the composition according to the present invention on the level of ethanol consumption under free-choice conditions parallel experiments have been carried out where the composition was introduced intragastrically, not into the test solution. The test results turned to be identical irrespective of the routes of administration of the composition according to the present invention.
Gas-liquid chromatography was used to determine the amount of ethanol in blood of animals of the test and control groups that were given the test solution for the period of 3 months. 90 minutes prior to slaughtering the animals they were introperitoneally administered with a 25% ethanol in combination with the composition according to the present invention in the ratio of 1:50 (test group).
The test results (Table 3) point to an essential increase (by more than 4 times) of ethanol in theblood of animals that were previously administered for a long time with the composition according to the present invention.
The rate of elimination of ethanol from blood depend, first of all, on activity of alcoholdehydrogenase (ADG) which has been studied against the background of an acute and chronical alcoholic intoxication.
Upon a single-time intraperitoneal administration, to animals of a 15% ethanol in the does of 4.5 g/kg of the body mass, 30 minutes thereafter the activity of alcohol dehydrogenase is 8.51 mM/min/l relative to the intact group; the composition additive according to the present invention inhibits activity of enzymes in the presence of ethanol which is 5.86 mM/min/l. In chronical experiments upon introduction of ethanol (passive alcoholization) over the period of 1.5 months of a daily administration of a 15% ethanol and ethanol in combination with the composition according to the present invention in the test does of 1 g/kg the data have been obtained which prove the results of the previous experiment (see Table 4).
Table 3
Effect of the composition according to the present
invention on elimination of ethanol after the addition
of a 25% ethanol 4.5 g/kg of the animals' bodyweight.
Experiment Statistical Content of
parameter ethanol in
blood, % - 2 2 3 1. Digested content (in
troduction of a 25%
ethanol) 7 M#m 0.72+0.14 2. 3-months' consumption
of a 15% ethanol (in
troduction of 25% et hanol) 14 M#m 1.0#0.14
P 0.2 3. 3-months' consumption
of a 15% ethanol in
combination with the
composition of the
present invention
(administration of 11 M+m 2,52+0.57 25% ethanol) P 0.01 4. 3-months' consumption
of a 15% ethanol in
combination with the
composition of this
invention (administ
ration of 25% etha- M+m 4.26+0.78
nol + composition), P 0.001
1::50 11
Table 4
Activity of alcoholdehydrogenase in blood serum and liver upon administration of a 15% ethanol in combination with the composition according to the present invention orally for 1.5 months.
activity of alcohol- Ethanol in Activity of z dehydrogenase accord blood alcohol- ing to Bonischoen denydrogenase method in blood serum by the Skursky method Serum Liver M@/min/l mM/min/l mM/mIn/l 1. 15% et@a- nol. # 3.1+1.17 3.15+0.14 47.02+1.91 16.21+1.4 2. 15v,0 etha- I nol+com position of this inventi on # 2.63+0.49 2.86+0.05 37.4+1.61 21.87+2.5 3. Composi tion of this in vention (aqueous solution 1:50) 2.76+0.33 2.21+0.05 34.39+2.6 4.32+0.4 4. Physiolo gical so lution 2.51+0.29 2.51+0.06 40.5+3.29 4.9+0.6 5. Intact # 2.6#0.33 2.46+0.09 40.51+1.3 4.14+0.3 Under conditions of free choice between a 15% ethanol and water (control group) and between a 15% ethanol with the composition according to the invention and water after 1.5 and 3 months of consumption the activity of alcohol dehydrogenase was studied prior to and after deprivation.The results thus obtained are shown in Table 5,
TABLE 5
Activity of alcoholdehydrogenase at a free choice
of the test solutions
Activity of alco- 1.5 months of 3 months of holdehydrogenase, consumption consumption mM/min/l Prior to after prior to after depriva- depri- depriva- de tion vation tion pri vation 1. 15% ethanol 2.7#0.26 3.61#0.48 2.64#0.27 4.3#0.63 2. 15% ethanol + composition of this invention 1.87#0.22 3.35#0.44 3.95+0.66 2.63+0.49 3. Intact 4.33+1.08 4.79+0.64 2.2+0.28 3.08+0.58 Therefore, the composition additive according to the present invention decelerates oxidation of ethanol in the liver by inhibiting activity of alcohol dehydrogenase.
Observations were carried out to study the lipoid and carbohydrate metabolism in animals upon administration of the composition according to the present invention against the background of a 3- and 6-months' alcoholization. To this end, over the period of 3 and 6 months the rats were intragastrically administered with 2 ml of the hereinbelow-specified solutions per 100 g of the body mass. In the control:
Group 1 distilled water; Group II - 15% ethanol; Group
III - 15% ethanol containing a 5% composition according to the present invention; Group IV - aqueous solution of the composition according to the present invention.
The results thus obtained are shown in Tables 6, 7, 8 and 9 hereinbelow.
Table 6
Variation of the content of neutral lipoids in the liver of rats fed with the solutions
for 3 months (in % of the total lipoids, M#m)
G r o u p s o f a n i m a l s
I II III IV V
control distillate aqueous solution 15% ethanol+ 15% ethanol
of the compositi- composition
on of this inven
tion of this in
vention
Cholesterol esters 14.5#1.10 14.5#0.49 12.5#0.93) 2.5#0.48) 15.0#1.21 % of variation 100 86 86 103
Triglycerides 13.6#0.55 17.2#1.11 ) 20.1+0.84 ) 20.6+1.77 3 ) 20.1+1.04 ) % of variation 127 148 151 148
Free fat acids 12.3#1.60 12.8#0.48 12.3#0.50 11.5#0.53 10.6#0.92 ) % of variation 100 96 90 83
Cholesterol 16.6#0.9 17.2#0.63 16.1#0.91 14.2#0.67) 15.3#1.22 % of variation 104 97 86 92
Residual fraction 32.5#1.05 38.3#0.97 39.0#1.02 41.2#1.30 39.0#1.00 1) p < 0.05; ) P < 0.02; ) P < 0.01 p - probability Table 7
Variation of the content of neutral lipoide in the liver of rats fed with the
solutions for 6 months (in % of the total lipoids, M#m)
G r o u p s o f a n i m a l s
I II III IV
distillate 15% ethanol 15% ethanol+ aqueous aolu
composition tion of the
of this in- compoaition
vention of the inven
tion
Cholesterol esters 16.9#0.69 16.52#0.70 16.62#0.35 16.74#0.27 15.81#0.14 % of variation 99 100 100 95
Triglycerides 15.16#0.21 13.88#0.12 18,19#0.26) 14.18#0.22) 13.64#0.42) % of variation 92 120 94 90
Free fatty acids 16.67#0.48 17.21#0.11 14.0#0.39) 17.30#0.37 18.66#0.88 % of variation 103 84 104 112
Cholesterol 17.28#0.26 17.07#0.16 16.61#0.69 16.72#0.89 17.06#0.19 % of varitation 99 96 97 99
Residual fraction 33.93#0.40 35.38#0.74 34.58#0.47 35.06#0.52 34.83#0.61 1) p < 0.05; 2) p < 0.02 Table 8
Variation of activity of lysosomal hydrolases in the liver of rats upon con
sumption of ethanol and the composition of this invention for 3 months
and 6 months (nanomol/ml/min,M#m)
Croups of animals 3 months 6 months
ss- @lycosidase ss- @alactosidase ss-@lucosidase ss-@alactosidase
Control 0.47#0.04 0.33#0.01 0.49#0.05 0.35#0.01 1. Distillate 0.43#0.01 0.35#0.01 0.54#0.08 0.43#0.02 % of variation 91 106 110 78 of the control
II. 15% ethanol 0.58#0.08) 0.37#0.04 0.87#0.09) 0.86#0.06 ) % of variation of the control 123 112 178 247
III. 15% ethanol + com- 0.50#0.05 0.35#0.06 0.66#0.08) 0.26#0.01 position of this invention % of variation of 106 106 135 75 the control
IV.Aqueous solution of composition of this 0.40#0.02 0.31#0.03 0.38#0.05 0.25#0.01) invention % of variation of the control 85 94 78 70 1) p < 0.05 2) p < 0.01; 3) p < 0.001 Table 9
Variation of the content of carbohydrate-containing biopolymers in the liver of
rats fed with ethanol and with the composition of the invention for 3 months
and 6 months (mg-%, M+m)
3 months 6 months
Groups of animals IIexoses IIexosamines IIexoses IIexosamines 1. Conytol 26.68#1.54 32.53#2.37 26.26@1.43 49.00#1.76 2. Distillate 18.67#1.12) 29.60#2.52 20.45#1.72 68.53#6.97)
% of variation
of the control 70 91 78 140 3.Aqueous solution
of the composition
of this invention 33.35#2.73) 36.02#1.47 28.91#1.34 102.43#7.63 )
% of variation of
the control 125 111 110 209 4. 15% ethanol + com
position of this 18.43#1.27) 28.10#2.65 19.71#1.10) 84.72+4.21 )
invention
% of variation
of the control 69 86 75 173 5. 15% ethenol 16.67#1.22) 25.84#1.77) 16.32#1.00) 30.22#5.41)
% of variation
of the control 62 79 62 62 1) p < 0.05; 2) p < 0.01; 3) p < 0.001 Then we have carried out pharmacological tests of the composition according to the present invention as an agent for improving general resistance of the organism.
For this purpose the effect of the composition according to the present invention on the heat-resistance of rats has been studied.
(I) Overheating of nondescript female rats (60 animals) is effected by irradiation with an UHF-field by means of an instrument for a microwave therapy with the frequency of 2,375 mHz - 17 mA for 10 days once a day over the period of 4 days. The test composition is administered in the dose of 2.5 ml/kg (intragastrically in all series of experiments) for 5 days before the beginning of irradiation and, on the say of experiment, one hour before irradiation. The death rate of rats is assessed after a 4-times' irradiation.
It has been found that during one day after the last irradiation in the control group 22% of the animals died, whereas among the rats administered with the composition according to the present invention the death rate was 11% (p < 0.01).
(2) Overheating of male rats of the Wistar line is effected in a thermostatted cabinet at the temperature of 430C. The test composition in the dose of 2.5 ml/kg is administered for the preventive purposes over the period of 20 days. The rectal temperature and death rate of the animals are assessed.
It has been found that in the control group 76% of the animals (28 animals out of 37) died, while against the background of the composition according to the present invention 56% of the rats died (22 rats out of 39; p < 0.001). The composition -provided no effect on the rectal temperature.
(3) Under the same conditions of overheating of male rats of the Wistar line the composition according to the present invention is administered prophylactically over 48 days in the dose of 1 ml/kg.
It has been found that in the control group 54% of rats (30 animals out of 55) died, while upon overheating against the background of a long-time administration of the composition according to the present invention the death rate was 42% (24 rats out of 57; p (0.001).
(4) Overheating of male rats of the Wistar line was effected in much the same manner. The test composition was administered in the dose of 1 ml/kg 50 minutes prior to overheating. The overheating duration is 40 minutes and 2 hours. The animals were killed by decapitation.
Tested were: the content of glycogen (herein and in other cases - by the Zeifter method); activity of hexokinase and glucoso-6-phosphatedehydrogenase (herein and in other cases - by the formation of nicotinamidedinucleotidephosphoric acid (NADPH).
It has been found that in overheating of the rats for 40 minutes the composition inhibited the drop of the content of glycogen, as well as of the activity of hexokinase and glucose-6-phosphate dehydrogenase in the liver (see Table 10 hereinbelow).
Upon overheating for 2 hours the test composition provided no effect on the level of the studied parameters.
Overcooling of male rats of the Wistar line was caused by placing the animals into a refrigerator chamber at a temperature of 5"C for 1 and 2 hours. The composition according to the present invention was administered in the dose of 1 ml/kg 60 minutes before cooling.
It has been found that upon overcooling of rats during the first hour there is observed a decrease of glycogen stock in the liver, as well as lowering of activity of hexokinase and glucose-6-phosphate dehydrogenase in this organ. A preliminary administration of the composition according to the present invention to the animals inhibited lowering of the studied parameters (see Table 11). Upon a 2-hours' cooling the composition according to the present invention provided no protective effect.
The effect of the composition according to the present invention on animals' resistance to a muscular fatigue has been also studied. To this end:
(1) Experiments are carried out on non-descript male mice with a mass of 28-33 g. The test composition is administered enterally by means of a probe to three groups of animals in three doses: 0.1, 0.15, 0.22 ml/20g one hour prior to the muscular work. The control animals are carried out on an "endless rope" apparatus.
The duration of mice run along a vertical downwardly moving rope till a complete exhaustion was diagnosed.
The dose of the composition extending the duration of mice run by 33% was found by graphical plotting.
TABLE 10
Effect of the composition according to the present
invention on variation of glycogen (mg-%), hexokinase
( mol of NADPH/min/g of the tissue),
glucose-6-phosphate dehydrogenase ( mol NADPH/min/g of
the tissue) upon (overheating 45 C).
Hexo- Glucoso-6-phos
Group of snimals
Glycogen ki- phatedehydroge- nase nase
1 2 3 4
40 minutes of overheating 1. ormal 3,226+148 0.42+0.025 1.80+0.61 2. Overheat
ing 2,387+209 0.34+0.19 1.57+0.095
p < 0.005 p < 0.020 p < 0.050 3. Overheat
ing + compo- 2,968+121 0.40+0.18 1.71+0.077 sition of
the present p < 0.030 p < 0.030 p < 0.030
invention 2 hours of overheating 1. Normal 4,628+207 0.50+0.019 1.56+0.058 2. Gverheat
in 2,175+271 0.31+0.027 1.17+0.095 p0.000I p < O.000I 3.Overheat ing + com
position 2,869+219 0.29+0.020 1.04+0.081
according to the pre
sent inven
tion p < O.060 p - in comparison with Groups 1-2 and Groups 2-3
TABLE 11
Effect of the composition of this invention on
variation of the content of glycogen (mg-%) and activity
of hexokinase ( mol NADPH/min/g of the tissue) and
glucose-6-phosphate dehydrogenase ( mol/NADPH/min/g of
the tissue) in the liver of rats upon overcooling (5 C) Group of animals Glycogen Hezokinase Glucoso-6
phosphate
dehydroge
nase
1 bour of overcooling 1 Normal 4109+195 0.51+0.017 1.62+0.078 2 Overcooling 2794+207 0.41+0.022 1.20+0.101
p < 0.0001 p < 0.003 p > 0.004 3 Overcooling +
composition of
this invention p < 0.020 p < 0.020
2 hours of overcooling l Normal 3078+189 0.63+0.017 1.57+0.075 2 Overcooling 1754+237 0.47+0.028 1.27+0.103 p < O.OOl p < 0.0001 p < 0.037 3 Overcooling + 1908+226 0.44+0.022 l.41+0.09l composition of
this invention
p - in comparison of Groups 1-2 and 2-3.
Activity of the studied composition was expressed in conditional units - stimulant effect units (SEU33).
As a result of tests it has been found that the muscular workability of mice was increasing proportional to the dose of the extract. Upon administration of the composition according to the present invention in the maximum dose (0.22 ml/kg) the workability increased by 41% as compared to the control (see Table 12 hereinbelow).
TABLE 12
Stimulant effect of the composition of this invention on duration of the muscular workability of mice in an "end
less rope" apparatus
Group of animals Duration of the run of the mice
minutes % p
Physiological solution (13) 27.0+2.1 100
Composition of the invention
0.1 ml/20 g (10) 30.0+1.8 111 0.5
0.15 ml/20 g (11) 32.0+2.8 118 0.5
0.22 ml/20 g (15) 38.0+2.7 141 0.001
Note: Shown in brackets is ttie number of animals.
(2) As a model of an experimental influence swimming of rats was used (herein and in other cases - male rats of the Wistar line) at the temperature of water of 300 C. The composition according to the present invention was administered to mice in the dose of 10 ml/kg one hour prior to the swimming. The ultimate duration of swimming was assessed (i.e. swimming till exhaustion).
It has been found that the rats' swimming duration in the control was 392.6+29.0 minutes, whereas against the background of the composition according to the present invention it was 519.4+40.0 minutes, i.e. by 32% longer (p = 0.023).
(3) The composition according to the present invention was administered one hour before the swimming in the dose of 1 ml/kg, whereafter the animals were allowed to swim for 15 minutes or 2 hours. The state of the animals was judged by the content of glycogen, activity of hexokinase and glucose-6-phosphate dehydrogenase in the liver.
It has been shown that the swimming of rats for both time limits specified hereinabove caused a decrease of glycogen content in the liver and lowering of the activity of hexokinase and glucose-6-phosphate dehydrogenase. A preliminary administration of the composition according to the present invention inhibited the decrease of the studied parameters after a 2-hours' swimming, but did not affect their level after a 15-minutes' muscular load (see Table 13).
(4) The composition according to the present invention was administered one hour before a 15-minutes' swimming. The content of cyclic adenosinemonophosphate in adrenal glands, and the content of cyclic guanosine monophosphate in adrenal glands and in the liver was determined by the radioimmune method by means of
Amersham equipment. A number of rats from the test and control groups were allowed to rest after swimming for one hour, whereafter the same characteristics were studied in them too.
TABLE 13
Effect of the composition of this invention on the
content of glycogen (mg-%) and activity of hexokinase
( mol NADPH/min/g of the tissue) and glucose-6
phosphate dehydrogenase ( mol NADPH/min/g/ of the
tissue) in the liver of rats in swimming (water
temperature 30-3 C).
Glucose
Group of Glycogen Hexokinase -6-phosanimels phate de
hydroge
nase
1 2 3 4
Swimming for 15 minutes 1 Normal 4216+216 0.50+0.019 1.44+0.068 2 Swimming 2993+278 0.31+0.029 1.01+0.094 p < 0.002 p < 0.001 p < 0.010 3 Swimming +
composition of
the invention 2902+202 0.35+0.015 0.98+0.101
Swimming for 60 minutes 1 Normal 3511+201 0.54+0.025 1.51+0.075 2 Swimming 2633+163 0.37+0.024 1.13+0.095
p < 0.004 p < 0.0001 p < 0.008 3 Swimming + 3089+133 0.44+0.021 1.39+0.071
composition of this invention p < 0.040 p < 0.040 p < 0.040
p - in comparison of Groups 1-2 and 2-3
The swimming of rats caused elevation of the level of cyclic adenosine monophosphate and cyclic guanosine monophosphate in adrenal glands, as well as reduction of the content of cyclic guanosine monophosphate in the liver (acute stress at an energy supply at the account of glycolysis). After the animals' rest for one hour the level of cyclic adenosine monophosphate and that of cyclic guanosine monophosphate were turned to normal values. The composition according to the present invention provided no effect on the content of cyclic adenosine monophosphate and cyclic guanosine monophosphate in the liver one hour after swimming came to its normal values (see Table 14 hereinbelow).
The composition according to the present invention was also studied for resistance of rats to hypokinesia which was induced by keeping animals in individual cellcages for 2 days. The test composition was administered during the entire period of hypokinesia in the dose of 1 ml/kg twice a day.
As a result of hypokinesia a reduction of glycogen stock in the liver was observed along with a decrease of concentration of cholesterol in adrenal glands and lowering of the activity of alcoholdehydrogenase (as determined by the method suggested by Schleisinger et al., 1966).
TABLE 14
Effect of the composition of this invention on the
content of cAMP in adrenal glands, cGMP in adrenal
glands and liver of rats after a muscular load and rest.
Group of cAMP, pmol cGMP, pmol animals adrenal glands adrenal liver
glands
1 2 3 4 1 Intact 8.5+0. 55 (7) 0.09*0.01 (7) 0.22+0.67 (7) 2 Swimming 17.9+1.8 (7) 0.30+0.04 (7) 0.14+0.035 (7) 15 minutes P < 0.05 pc p < 0.001 3 Swimming for
15 min and 8.1+0.63 (6) 0.18+0,02 (7) 0.059+0.045 (6)
rest for 1h p < 0.05 p < 0.OOl p < 0.001 4 Swimming for
15 min and
the composi
tion of this
invention 17.3+1.87 (7) 0.25+0.06 (6) 0.25+0.06 (6) 5 Swimming for 15min+
composition
of this in- 9.0+0.65 (6) 0.14+0.01 (7) 0.136+0.009 (7)
vention p < 0.0@ p < 0.0001
and rest
for 1 hour
In the animals administered with the composition
according to the present invention the reduction of the
studied parameters after hypokinesia was less pronounced
(see Table 15 hereinbelow).
TABLE 15
Effect of the composition of this invention on the
content of cholestrol in adrenal glands (mg/g), the
content of glycogen (mg-%) and activity of alcohol
dehydrogenase (mol NADPH/min/g of the tissue) in the
liver of rats under hypokinesia (2 days).
Group of animals Cholesterol Glycogen Alcohol dehydro- genase 2 2 3 4 1 Normal 44+1.6 3975+222 5.04+0.234 2 Hypokinesia 96+2.4 2862+251 5.90+0.250
p < 0.01 p < 0.004 p 0.02 3 Hypokinesia +
composition of
this invention p < 0.03 p < 0.04 p < 0.01 p - in comparison of Groups 1-2 and 2-3
We have also studied the effect produced by the composition according to the present invention on resistance of animals to different chemical factors.
(I) As a model of an injuring effect a hexenal narcosis was used. The composition according to the present invention was administered to rats in the doses of 2.5, 5.0, 10.0 ml/kg; 2 hours thereafter hexenal was administered intraperitoneally in the dose of 19.8 mg/100 g. The duration of the side posture state of the animals was assessed.
It has been found that the duration of the hexenal narcosis of the control rats was 90.6+3.9 minutes, while against the background of the composition according to the present invention administered in the dose of 2.5 ml/kg it was 85.5+5.4 min, in the dose of 5.0 ml/kg 75.7+3.1 min (83.6%, p=0.009), in the dose of 10.0 ml/kg - 72.9+3.7 (80.5%, p = 0.005 that is, the composition according to the present invention exerted an awakening dose-depending effect.
(2) In experiments on mice narcosis was caused by means of sodium thiopental in three doses: 62.5, 75.0 and 100 mg/kg intraperitoneally. The composition according to the present invention was introduced in the does of 10.0 ml/kg two hours before the injection of thiopental. The speed of occurrence of the side posture was determined, as well as the duration of the side posture period and the death rate of the animals was assessed.
It has been found that out of the mice administered with thiopental (62.5 mg/kg) against the background of the composition according to the present invention the side posture was acquired by 22% of the animals, whereas in the control (thiopental) - 100% of the mice (p = 0.001). The duration of the side posture period in the control was 53.5 minutes, in the experiment - 120 minutes (p < 0.05).
In the group of mice administered with thiopental in the dose of 75 mg/kg 28% of the animals died, whereas in the group of rats administered with thiopental against the background of the composition according to the present invention 12.5% of the animals died (p < 0.001). In the control group the side posture period lasted for 30.0+0.0 minutes, whereas against the background of the composition according to the present invention - 260+0.0 minutes (p < 0.05). The death rate of the animals in both groups was the same.
The composition according to the present invention has been also studied for certain aspects of carbohydrate metabolism. To this end:
(I) In experiments on intact animals under conditions of a conventional feeding diet the composition according to the present invention was administered twice a day over 5 days. In this and subsequent series of experiments the concentration on glucose in blood was determined by the anthrone method, the content of glycogen in the liver - by the Zeifter method. It has been found that a 5-days' administration of the composition according to the present invention to intact animals caused a certain increase of sugar concentrations in blood and of glycogen in the liver (see Table 16).
(2) The study of carbohydrate metabolism has been performed on rats subjected to starvation for 18 or 48 hours. The test composition was administered in the dose of 1 mg/kg 1 hour prior to slaughter of the animals. The content of sugar in blood, the level of insulin in blood serum were determined by the radioimmune method.
It has been shown that a 18-hours' starvation of rats has caused reduction of the glycaemia level. The test composition inhibited reduction of the sugar content in blood (see Table 16). The rats' starvation for 48 hours has caused a certain reduction of the sugar content on blood and glycogen content in the liver.
This was accompanied by a lowered concentration of insulin in blood serum.
In a preliminary 5-days' administration of the composition according to the present invention to the animals only a trend was observed towards preservation of a previous level of sugar in blood and of glycogen in the liver. In this case the content of insulin in blood was certainly higher than in the control (subjected to starvation) animals (see Table 16 hereinbelow).
(3) The effect of the composition according to the present invention on the carbohydrate metabolism was studied on rats fed with an excessive diet. The composition was administered in the dose of 1 ml/kg 1 hour before slaughter.
Under conditions of an excessive diet of the rats the studied extract provided no effect on the concentration of sugar in blood, but it certainly increased the content of glycogen in the liver and reduced the level of insulin in blood (see Table 16 hereinbelow).
TABLE 16
Effect of the composition of this invention on some
parameters of the carbohydrate metalolism in rats.
Blood sugar, Liver gly- Blood in
Group of mg-% cogen, insulin
animals mg-% @UN/m 1 2 3 4
Normal diet of rats
Normal 91.0+2.7 (9) 4966+406 (9) Composition 100.5+1.78x(13) 6071+250x(10) of this in- vention Starvation for 18 hours
Normal diet (10) 106.8+3.7
Starvation (8) 83.8+2.0x
Starvation + 1ml/kg
of composition of
this invention
30 minutes
before slaughter
ing (10) 106.0+4.2x Starvation for 40 hours
Normal diet (10) 116.5+5.0 5059t452 17.56+1.12
Starvation (10) 86.0+5.0x 495+257x 9.56+0.69
Starvation +
composition of
this invention 91.0+5.0 593+151 14.5+1.Ox Excessive diet of rats
Without composi- 119.0+4.3 4996+406 22.8+2.3 sition of this
invention (10)
Composition of this 122.3+2.7 6071+250x 17.3+1.19x
invention
x) p < 0.05,
Composition of this invention is administered in
tragastrically in the dose of 1 ml/kg twice a day
over 5 days. Shown in brackets is the number of
animals.
We have studied antioxidation properties of the composition according to the present invention. To this end, in order to activate a peroxy oxidation of lipoids, in rats of the Wistar line (40 animals) stress was caused by suspending them by the neck skin fold for 24 hours. The test group of animals was administered once with the composition of the present invention in the dose of 1 ml/kg prior to suspending. The accumulation of lipoid peroxides in the liver was assessed by the concentration of malonic dialdehyde in this organ.
It has been found that the composition according to the present invention caused no changes in the content of malonic dialdehyde in the liver of intact rats. In the rats which underwent the stress treatment by content of malonic dialdehyde in the liver increased 6 fold, whereas in the case of stress against the background of the composition according to the present invention the rate of accumulation of malonic dialdehyde was noticeably smaller (normal - 86.5+29.0; stress 452+20; stress + composition according to the present invention - 296 + 15; p = 0.001). Consequently, the composition according to the present invention possesses antioxidant properties.
We have also studied biochemical characteristics of human beings administered with the composition according to the present invention against the background of alcohol ization.
Under clinical conditions the effect of the composition according to the present invention on the rate of elimination of ethanol from blood and on activity of blood alcohol dehydrogenase, as well as on activity characteristics of lysosomal hydrolases, the level of protein-combined hexosoamines and on fractions of neutral lipoids was studied. The first group of patients who took part in the studies consisted of persons suffering from chronic alcoholism and subjected to a stationary treatment; the second group was composed of persons belonging to the Mongoloid race genetically intolerant to alcohol; the third group substantially healthy Europoids who did not abuse alcohol.
Under conditions of a double blind control the patients took a 40% ethanol with the composition according to the present invention (1:50) or an aqueous solution of this composition. The volume of the taken liquid was 200 ml per 70 kg of the bodymass. The intervals between intakes were 4 days. Blood from vein was taken prior to the liquid intake, 1 hour, 2 and 4 hours thereafter for biochemical investigations. The test results are shown in Tables 17, 18, 19, 20, 21 and 22 hereinbelow.
Activity of #galactosidase in blood serum
of volunteers (nanomol/ml/min,M+m)
40% ethanol
No. Groups 1 2 4
Backgro hour hour hours 1 2 3 4 5 6 Healthy euro
peoids 5.95+0.62 6.66+0.21 19.94+1.22 ) 35.57+1.63 )
% of varia
tion 112 335 598 2. Mongoloids
5.77#0.94 5.92#0.68 12.15#0.87 ) 12.61#0.98 ) % of varia
tion 103 211 219 3.Alcoholism
suffering pa tents
8.79+0.67 21.92+0.94 7.98+0.20 10.46+0.91 % of varia
tion 249 91 122
backgro- I 2 4
und hour hours hours 7 7 8 9 10 1. 5.72+0.19 5.09+0.27 4.06#0.44) 6.85+0.481) 89 71 120
2. 6.89+0.47 6.30+0.33 6.87+0.57 7.50+0.44
91 99 109
3. 11.72+0.72 11.95+0.83 13.94+0.85 24.26#1.58 ) 102 119 207
Table 17 (continued)
40% ethanol+ composition of this invention backgro- 1 2 4
@@@@ @@@@@ @@@@@ und
I 11 12 13 14 1. 5.90#0.42 5.78#0.54 6.55#0.42 18.0#1.6 ) 98 111 305 2. 6.33+0.44 9.39+0.71 9.23#0.84 16.4+1.5
148 146 259 3.10.45+0.39 15.15+0.722) 14.00+0.862) 12.8+0.92) 145 134 122
1) p < 0.05 2) p < 0.01 3) p < 0.001
Table 18
Variation of the content of hexosamines in
human blood serum (mg-%), M#m NN Groups of 1. Healthy europeoids volunteers backgro- I 2 4
und hour hours hours 1 2 3 4 5 6 1. 40% ethanol 72.57#3.55 66.93#4.10 66.00# 61.20# +2.51 +2.62 7a of varia
tion vs.
the back
ground 92 91 85 2. 40% ethanol+
composition
of this in
vention 53.33#2.39 50.4#3.85 42.53# 50.53# #1.79) #3.27 % of variati
on vs. the
background 95 80 95 3.Composition
of this in- 72.16± 4.01 94.13±3.92 93.441 87.52i vention 72.16± t.01 94.13+3.92 ion
#4.04 ) #1.90) % of varia
tion vs. the
background 131 130 122
Table 18 (continued)
II Healthy mongoloids
backgro- I 2 4
und hour hours hours
I 7 8 9 10 1. 48.93+3.31 46.40+1.72 48.64+2.93 53.20+3.75
95 99 109 2. 84.60#3.70 63.20#1.21 ) 100.64#3.70) 93.33#4.22 75 119 110 3. 36.68#3.71 45.21#3.00) 53.20#1.52) 53.20#2.74 ) 127 149 149
Table 18 (continued)
III.Alcoholism-suffering patients
NN
backgro- 1 2 4
und hour hours hours 1 11 12 13 14 1. 68.30+2.76 56.06+2.811) 54.64+3.431) 57.37+3.321) 82 80 84 2. 75.94+4.41 73.71#3.10 66.97+5.37 70.42+4.16
97 88 93 3. 60.11+4.81 62.27+3.15 69.94#3.00) 60.23+3.30
103 116 100
1) P < 0.05
2) p < 0.01 3) p < 0.001 Table 18 (continued)
II Healthy mongoloids NN
backgro- 1 2 4 1 7 8 9 10
1. 48.93+3.31 46.40+1.72 48.64+2.93 53.20+3.75
95 99 109
2. 84.60+3.70 63.20+1.213) 100.64+3.702) 93.33+4.22
75 119 110 3. 36.68#3.71 45.21#3.00) 53.20#1.52) 53.20#2.74 ) 127 149 149
Table 18 (continued)
III.Alcoholism-suffering patients
NN
backgro- I 2 4
und hour hours hours
1 11 12 13 14
1. 68.30+2.76 56.06+2.811) 54.64+3.431) 57.37+3.321) 82 80 84
2. 75.94+4.41 73.71+3.10 66.97+5.37 70.42+4.16
97 88 93
3. 60.11+4.81 62.27+3.15 69.94+3.001) 60.23+3.30
103 116 100
1) P < 0.05 2) p < 0.01
3) p < 0.001 Table 19
Variation of the content of fractions of neutral
lipoids in human blood serum of persons consumed 40 ethanol (in %0 of the total lipoids, M+m)
NN Fractions I group
backgro- I 2 4 und hour hours hours 1.Cholesterol 1) esters 21.72#1.81 27.03#1.32@) 23.06#1.15 23.95#0.90 % of varia
tion 125 106 110 2. Triglyceri
des 17.40+0.72 16.53+0.97 19.11+0.75 19.08+0.78
% of varia
tion 95 110 110 3. Free fatty
acids 17.06*0.65 16.88+0.50 15.87+0.42 17.24+0.95
% of varia
tion 99 93 101 4. Choleste
rol 19.64+0.86 18.25+0.87 19.04+0.24 19.08+0.48
% of varia
tion 93 97 97 5.Residual
combined
fraction 24.18+0.52 24.29+1.85 22.92+0.73 20.65+0.70
Table 19 (continued)
NN II group
backgro- I 2 4
und hour hours hours 1 7 8 9 10 1. 26.66+1.19 27.89+1.33 21.22+0.54 29.62+1.44
105 80 111
Table 19 (continued) 1 7 8 9 10 2. 17.45+0.76 16.63+0.86 16.48+0.71 19.02+0.22
95 94 110 3. 15.10+0.47 16.57+1.08 18.45+0.572) 13.87+1.15
110 122 92 4. 18.54+0.50 17.79+0.26 20.04+0.66 17.03+0.71
96 108 92 5. 22.25+0.31 21.12+0.64 23.75+0.97 29.46+0.93 Table 19 (continued) NN III group
backgro- 1 2 4
und hour hours hours l 11 12 13 14 1. 25.90#2.14 26.47+2.16 22.66+1.05 25.37+2.48
102 88 98 2. 15.28+1.05 15.40+0.76 16.37+0.69 15.92+1.24
101 107 105 3. 15.29#1.35 18.64#47) 29.29#0.47) 16.69#1.99 122 126 109 4. 17.94+0.99 18.71+1.74 21.65+1.96 19.82+0.71
104 121 111 5. 25.60+1.68 20.78+0.81 20.03+1.16 22.13+1.29 1) p < 0.05; 2) p < 0.Ol Group I - healthy europeoids; Group II - healthy mongoloids;
Group III - alcoholism-suffering
patients
Table 20
Variation of the content of fractions of neutral
lipoids in human blood serum of patients consumed
aqueous solution of the composition of this inven
tion (in % of the total lipoids, M+m) ; Fractions G r o u p 1 backgro- I 2 4
und hour hours hours 1 2 3 4 5 6 1.Cholesterol 23.07+1.47 22.74+2.10 23.44+0.54 23.10+0.89
esters
% of varia
tion 99 102 101 2. Triglycerides
17.24+0.82 16.75#0.67 20.49+1.29 17.63+0.75 of varia
tion 97 119 102 3. Free fatty
acids 16.14+1.20 17.17+0.39 16.85+0.42 17.90+0.63
% of varia- tion 110 104 111 4. Cholesterol 17.43+1.57 18.69#1.93 19.97+0.54 17.89+0.93 % of varia
tion 107 115 103 5.Residual
combined
fraction 26.12+2.30 24.05+1.70 19.25+0.74 23.48+0.71
Table 20 (continued)
NN G r 0 U p II
backgro- 2 2 2 3
und hour hours hours 1 7 8 9 10 1. 23.12+1.32 21.34+1.38 23.59+0.54 23.17+0.46
92 102 100 2. 16.79+2.02 18.99+0.47 17.73+0.33 18.08+0.56
113 106 108 3. 17.77+1.03 18.05+0.48 16.41+0.67 17.38+0.56
102 92 98 4. 18.09+0.60 20.33+0.37 20.51+0.55 20.88+0.44
112 113 115 5. 24.23+1.60 21.29+0.92 21.76+0.46 20.49+0.52
Table 20 (continued)
NN G r o u p III
backgro- I 2 3
und hour hours hours 1 11 12 13 14 1. 22.49+0.44 24.87+0.54 24.43+0.86 24.05t0.62 111 109 107 2. 19.36+1.0 17.16+0.48 17.29+0.39 17.58+0.84
89 89 91 3. 17.77+0.65 17.77+0.55 17.76+0.36 15.05+0.99
100 100 85 4. 19.37+0.35 19.39+0.43 18.46+0.79 17.34+0.49
100 95 90 5. 21.01+0.61 20.81+0.82 23.06+1.10 25.90+1.13
Group I - healthy europeolds, Group II- healthy mongoloids,
Group III - alcoholism - suffering patients.
Table 21
Variation of the content of fractions of neutral
lipoids in human blood serum of patients consumed
a 40% solution of ethanol (in qO of the total li
poids, M#m) with the composition of this invention
NN Fractions G r J U p 1
backgro- 1 2 4
und hour hours hours 1 2 3 4 5 6 1. Cholesterol 24.35+2.04 23.91+0.67 22.04+0.41 21.53+0.68
esters
% of varia
tion 98 91 88 2. Triglyceri
des 16.41+0.71 18.14+0.30 18.48#1.24 19.51+0.691)
% of varia
tion 111 113 119 3. Free fatty
acids 15.96#0.76 16.19+0.57 16.30+0.26 15.90+0.24 % of varia
tion 101 102 106 4. Cholesterol 19.21+0.86 18.87+0.38 18.06+0.84 20.06+1.58
% of varia
tion 98 94 104 5. Residual
combined
fraction 24.07+1.93 22.89+0.55 24.52+1.61 22.94+1.17
Table 21 (continued)
NN G r o u p II
backgro- 1 2 4 @ @ @
und hour hours hours 1 7 8 9 10 1. 22.30+1.01 24.32+0.55 23.15+1.45 22.89+0.70
109 104 103 2. 19.95+1.71 18.15#0.55 18.87+2.11 19.47+0.28
91 95 98 3. 16.12+0.46 16.17#1.10 15.83+0.58 16.95+0.84
100 98 105 4. 17.84+0.28 18.02+0.93 17.66+0.89 19.22+0.45
101 99 108 5. 23.79+2.03 23.34#0.60 24.46+1.45 21.47+1.33
Table 21 (continued)
NN G r o u p III
backgro- I 2 4
und hour hours hours 11 @ 11 12 13 14 1. 24.60#0.59 24.05#0.62 24.26#0.34 22.94#0.90 100 101 95 2. 17.05+0.52 16.50+0.56 17.43+0.49 18.77+0.66
97 102 110 3. 15.95+0.53 16.63+0.41 17.00+0.50 17.01+0.52
104 107 107 4. 18.37+0.73 17.85+0.44 19.07#0.42 19.89+0.49
97 104 108 5. 24.03+0.79 24.97*1.08 22.24+1.20 21.39+0.51 1) P0.0l Group 1 - healthy europeoids; Group II - healthy
mongoloids; Group III - alcoholism-suffering patients.
Table 22
System ADG-ethanol, in patients consumed solutions
of ethanol and composition of this invention
NN Fractions 40% ethanol
backgrou- I 2 4
und hour hours hours 1 2 3 4 5 6 1. pati- A D G 0.46#0.16 1.24#0.56 1.83+0.58 2.39+0.66 2. ents etha
nol 0 0.27+0.01 0.198+0.023 0.113+0.014 3. mon- A D G 2.81+0.97 3.15+0.67 3.17+0.87 3.15+0.89 4. golo- egha- 0.012#0.007 0.174#0.033 0.188#0.024 0.064# ids #0.028 nol 5. healthy A D G 2.90#0.58 1.73#0.29 3.04#0.42 0.52#0.28
euro5. pe- etha- 0.023# 0.263# 0.0124# 0.035# oids nol +0.002 +0.028 +0.013 +0.000035
Table 22 (continued)
NN 40% ethanol + composition of this invention
backgro- I 2 4 uBd hour hours hours 1 7 8 9 10 1. 2.28+0.68 3.56+0.66 1.85+0.39 0.70+0.25 2. 0.138+0.032 0.182+0.054 0.203+0.022 3. 1.74#0.32 1.69+0.31 2.34+0.87 1.57+0.31 4. 0 0.206+0.023 0.105+0.029 0.103+0.033 5. 2.56+0.23 1.78+0.68 2.35+0.57 0.69+0.34 6. 0.049# 0.174#0.025 0.174#0.016 0.086#0.01 #0.0004 Table 22 (continued)
NN Composition of this invention
background I 2 4
hour hours hours 1 11 12 13 14 1. 1.06+0.46 0.79+0.27 1.79+0.35 1.67+0.47 2. 0.04+0.012 0.14+0.014 0.076+0.024 0.082#0.018 3. 2.48+0.64 1.59+0.58 1.69+0.47 2.37+0.76 4. 0 0 0 0 5. 1.00+0.37 1.64+0.40 1.37#0.47 1.27+0.36 6. 0.006+0.000008 0.042+ 0.076+0.035 0.015+ #0.032 #0.00004 Measurement units:ADG (i/i); ethanol
ADG - alcoholdehydrogenase
We have also carried out for 10 months testing of the composition according to the present invention on 8,000 persons. To this end, alcoholic beverages containing the composition according to the present invention were used. The persons included in observations did not take any other alcoholic beverages during the entire period of tests. The total reduction of the total consumption over the period of 10 months constituted 28.01%.
Within 10 months of tests the number of alcoholic psychoses in this group of persons reduced to four cases compared for 12.5 cases on the average over the preceding 6 similar periods.
The course of alcoholic intoxications has also changed: easier hang-over states, a lowered demand for a hang-over drink due to the appearance of somatic complaints inhibiting continuation of heavy-drinking periods in alcohol-abusing persons.
No demographic and social excesses were noted among persons included in observations.
Therefore, on the ground of the carried out studies and experiments a conclusion may be made that the general effect of the composition according to the present invention directed against negative after-effects of the alcohol consumption is composed of the effects provided by the composition ingredients on the main biological signs of alcohol:
- membranotropic effect of ethanol is lowered due to normalization of the membrane stability owing to regulation of the synthesis of cholestrol, its esterification and inclusion into the structure of membranes. This also results in normalization of activity of membrane-combined enzymes and other permeability characteristics according to the principle of Vitamin P - activity.
-Oxidation of ethanol is effected mainly in the liver with exhaustion of the oxidized form of nicotinamidedinucleotide NAD+. Other oxidizing processes occurring with the use of NAD+ are inhibited.
The ingredients of the composition according to the present invention act as hydrogen ion acceptors and contribute to lowering of the ratio NADH/NAD+.
-in the course of oxidation of ethanol in the organism the most toxic metabolite - acetaldehyde - is formed which when present in tissues is responsible for toxicological and narcotic characteristics of ethanol.
The rate of oxidation of ethanol and acetaldehyde depends first of all on activity of alcohol dehydrogenase and acetaldehyde dehydrogenase. The ingredients of the composition according to the present invention are capable of lowering the activity of alcohol dehydrogenase by decelerating oxidation of ethanol and, furthermore, of entering into competitive relations with ethanol as a substrate for alcohol dehydrogenase. In doing so, due to conformation of alcohol dehydrogenase there is effected oxidation of not ethanol, but, first of all, of the competing substrate incorporated in the composition according to the present invention;
-calorigenic effect of ethanol1 owing to which it is a successful competitor in respect of other sources of energy while being superior to them by the availability criterion. This causes the narrowing of the main metabolic chain of conversion of a number of edible substances due to a competitive alienation of specific dehydrogenases and their prosthetic groups. The composition according to the present invention contributes to conservation and, upon a longtime consumption of alcohol, to restoration of other energy supply routes, in particular through gluconeogenesis.
The carried out tests of the composition according to the present invention in experiments on animals1 in obsevations on volunteers have shown that the com position of this invention has an ability of providing rational ways for a high resistance and recovery of the organism. In all cases of extreme loads on animals (of both physical, chemical and biological character) a clearly-pronounced stress-protecting effect is observed. In addition thereto, the composition according to the present invention has specific biological properties of inhibiting the formation of a physical dependence on alcohol and of lowering detrimental effects of its toxic metabolites.
A wide range of biological action of the composition according to the present invention is explained by the fact that it comprises an indispensible set of substrates ensuring optimal ways of metabolism directed to the preservation of energy resources of the organism by way of synthesis of carbohydrates from noncarbohydrate metabolites through gluconeogenesis.
ExamPle 1
A composition contains the following ingredients, mg/g: leukodolphinidine 120, leukocyanidine - 80, leukopelargonidine - 45, (-)epigallocatechin - 42, (+)gallocatachin - 31, (-)epicatchin - 29, (+)catechin 60, (-)epicatechingallate - 18, kaempferol-3-monoglucoside - 17, quercetin-3-monoglucoside - 22, myricetin-3-monoglucodide - 14, quercetin-3-glucoside 24. astragalin - 13. lignin - 75, D-glu@ose - D-fructose - 64, saccharose - 33.5, raffinose - 24, arabinose - 25, xylose - 31.6, pectine - 20, lysine 3.4, histidine - - 0.2, arginine - 0.4, aspartic acid 4.3, threinine - - 1.1, serine - 2.0, glutamic acid 3.0, proline - 3.3, glycine - 2.2, alanine - 3.8, cystine - 0.3, valine - - 1.8, methionine - 0.4, isoleucine - 0.8, leucine - - 2.8, tyrosine - 0.5, phenylalanine - 0.3, tartaric acid - 4.22, malic acid 3.8, citric acid - 4.0, ascorbic acid - 4.0, α - ketoglutaric acid - 1.9, fumaric acid - 2.1, galacturonic acid - 2.2, glyceric acid - - 1.8, glycolic acid - 1.7, glycouronic acid - 3.0, oxalic acid - 2.3, succinic acid - 5.0, skikimic acid - 3.0, a-amyrine 0.4, ss-amyrine - 0.4, loupeol - 0.3, taraxasterol 0.4, taraxerol - 0.4, germanicol - 0.3, obtusifoliol 0.8, citrostadienol - 0.7, ss-cetosterine - 3.2, stigmaiterol - 1.0, kaimpesterol - 0.8, oxymatairesinol - 2.9, matairesinol - 2.3, pinoresinol - - 2.5, liovyl 2.7, isolariciresinol - 2.7, olivyl - - 1.9, querinol arabinoside - 6.2, querinol xyloside - - 3.8, parahydroxybenzoic acid - 1.2, protocatechinic acid 3.5, gallic acid - 1.9, vanillic acid - 4.3, syringe acid - 4.1, vanilline - 1.5, syringe aldehyde - 1.3, sinapic aldehyde - 0.9, coniferyl aldehyde - - 1.3, octadecanolferulate - 1.5, eicosanolferulate - - 1.4, docosanol ferulate - 1.1, tetracosanolferulate - - 0.5, hexacosanolferulate - 0.5.
This composition in the amount of 5 g is dissolved in 100 ml of a 40% aqueous-alcoholic solution.
The resulting aqueous-alcoholic solution has a red-brown colour, a weak characteristic scent and a soft astringent taste. The solution has a low toxicity. The LD50 is 36.5 m1/1.000 g of body mass of a rat. The solution is capable of providing rational ways for resistance and recovery of the organism, suppresses the formation of a physical dependence on alcohol and lowers detrimental effects of its toxic metabolites.
Example 2
A composition contains the ingredients similar to those specified in Example 1 in the following amounts, mg/g: leukoanthocyanes - 197.1, catechins - 137.7, flavanols - 72.9. lignin - 61.2, reducing sugars 410.76, pectin - 16.2, free aminoacids - 24.3, organic acids - 32.4, sterols, methylsterols, dimethylsterols 1.78, lignans - 12.1, lignan glycosides - 8.1, phenolic acids - 12.1, phenolic aldehydes - 4.05, alkylferulates - 4.05.
This composition in the amount of 5 g is dissolved in 100 ml of a 40% queous-alcoholic solution. The resulting aqueous-alcoholic solution has a red-brown colour, a weak, specific scent and a soft, slightly sweet, astringent taste. The solution has a low toxicity: the LD50 is 41.2 ml/1.000 g of body mass of a rat.
The solution has an ability of ensuring rational ways for resistance and recovery of the organism, slightly inhibits the formation of a physical dependence on alcohol and reduces, to a cetain extent, negative effects of its toxic metabolites. The composition has a low activity which is even not recorded in a number of biological tests.
Example 3
A composition contains the ingredients similar to those specified in Example 1 hereinbefore in the following amounts, mg/g: leukoanthocyanes - 219, catechins - 153, flavanols - 81, lignin - 68, reducing sugars - 345.17, pectin - 18, free aminoacids - 27, organic acids - 36, sterols - 4.5, methylsterols - 1.35, dimethylsterols - 1.98, lignans - 13.5, lignan glycosides - 9, phenolic acids 13.5, phenolic aldehydes 4.5, alkylferulates - 4.5.
This composition in the amount of 5 g is dissolved in 100 ml of a 40% aqueous-alcoholic solution. The resulting solution is of a red-brown colour, it has a weak, specific scent and a soft, astringent taste. The solution has a low toxicity: its LD50 is 36.5 ml/ 1,000 g of body mass of a rat.
The solution is capable of providing rational ways for resistance and recovery of the organism; it inhibits the formation of a physical dependence on alcohol and slightly lowers negative effects or its toxic metabolites.
Example 4
A composition contains the ingredients similar to those specified in Example 1 in the following amounts, mg/g: leukoanthocyanes - 270, catechins - 187, flavanols - 99, lignin - 83, reducing sugars - 197.5, pectin - 22, free aminoacids - 33, organic acids - 44, steols - 5.5, methylsterols - 1.65, dimethylsterols - 2.42, lignans 16.5, lignan glycosides - 11, phenolic acids - 16.5, phenolic aldehydes - 5.5, alkylferulates - 5.5.
This composition in the amount of 5 g is dissolved in 100 ml of a 40% aqueo-alcoholic solution. The resulting has a red-brown colour, a weak, specific scent and a soft, astringent taste. The solution is of a low toxicity: its LD50 is 36.5 ml/1,000 g of body mass of a rat.
The solution is capable of ensuring rational ways for resistance and recovery of the organism, inhibits the formation of a physical dependence on alcohol and lowers negative effects of its toxic metabolites.
Example 5
A composition contains the ingredients similar to those of Example 1 in the following amounts, mg/g: leukoanthocyanes - 297, catechins - 205, flavanols 109, lignin - 91, reducing sugars - 120.6, pectin - 24, free aminoacids - 36, organic acids - 48, sterols - 6, methylsterols - 1.8, dimethylsterols - 2.6, lignans 18, lignan glycosides - 12, phenolic acids - 18, phenolic aldehydes - 6, alkylferulates - 6.
The composition in the amount of 5 g is dissolved in 100 ml of a 40% aqueo-alcoholic solution. The resulting solution has a red-brown colour, a pronounced , specific odour and an astringent taste. The solution has a low toxicity: its LD50 is 33.3 ml/1,000 g of body mass of a rat.
The solution is capable of ensuring rational ways for resistance and recovery of the organism; it inhibits the formation of a physical dependence on alcohol and diminishes detrimental effects of its toxic metabolites.
Claims (18)
1. A pharmaceutical composition for administration inter alia to inhibit the development of a pathologival addiction, which comprises the following ingredients, mg/g:
leukoanthocyanes 219-270
catechins 153-187
flavanols 81-99 1 ignin 68-83
sugars 216-264
pectin 18-22
free aminoacids 27-33
organic acids 36-44
sterols 4.5-5.5
methylsterols 1.35-1.65
dimethylsterols 1.98-2.42 1 ignans 13.5-16.5
lignan glycosides 9-11
phenolic acids 13.5-16.5
phenolic aldehydes 4.5-5.5
alkylferulates 4.5-5.5.
2. A composition to claim l containing leucodolphinidine, leucocyanidine or leucopelargonidine.
3. A compositon according to claim 1 or claim 2 containing (-) epigallocatechin, (+) gallocatechin, (-) epicatechin, (+) catechin or (-) epicatechingallate.
4. A composition according to any of claims 1 to 3 containing kaempferol-3-monoglucoside, quercetin-3monoglucoside, myricetin-3-monoglucoside or astraglain.
5. A composition according to any of claims 1 to 4 containing D-glucose, D-fructose, sucrose, raffinose, arabinose, or xylose.
6. A composition according to any of claims 1 to 5, containing lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, cystine, valine, methionine, isoleucine, leucine, tyrosine or phenylalanine.
7. A composition according to any of claims 1 to 6 containing tartaric acid, malic acid, citric acid, ascorbic acid, a-ketoglutaric acid, fumaric acid, galacturonic acid, glyceric acid, glycolic acid, glycouronic acid, oxalic acid, succinic acid, or shikimic acid.
8. A composition according to any of claims 1 to 7 containing ss-cetosterol, stigmasterol, kaempesterol, obtusifoliol, citrostadienol, a-amyrin, lupeol.
taraksterol, taraxasterol, or germanicol.
9. A compositon according to any of claims 1 to 8 containing oxymatairesinol, matairesinol, pinoresinol, liovyl, isolariciresinol or olivyl, querinol arabinose or querinol xyloside.
10. A composition according to any claims 1 to 9 containing parahydroxybenzoic acid, protocatechinic acid, gallic acid, vanillic acid ot syringic phenolic acids.
11. A composition according to any of claims 1 to 10 containing vanillin, syringic aldehyde, sinapic aldehyde or coniferyl aldehyde.
12. A composition according to any of claims 1 to 11 containing alkyl esters of ferulic acid with the alcohol moeity being represented by octadecanol, eicosanol, docosanol, tetracosanol, or hexacosanol.
13. An alcoholic beverage comprising the following , per 1,000 decalitres of the beverage: 473-493 kg of a compostion according to any of claims 1 to 12;
4,950-5,050 kg of a 40 fruit alcohol,
95-105 kg of sugar,
1.8-2.2 kg of citric acid,
28-32 kg of a tint; and
4,317.8-42.2 kg of an aqueous-alcoholic liquid.
14. A process for producing an alcoholic beverage according to Claim 13 comprising:
- blending 473-493 kg of a composition according to any of claims 1 to 12, 4,950-5,050 kg of a 400 fruit alcohol, 95-105 kg of sugar , 1.8-2.2 kg of citric acid, and 28--32 kg of a tint to form a blend;
-adding the resulting blend with an aqueous-alcoholic liquid in an amount necessary to obtain 1,000 decalitres of the beverage;
-a triple succesive heat treatment of the resulting blend for 5-8 hours at a temperature within the range of from 70 to 80"C; -cooling of the blend after the heat-treatment thereof for a period of time sufficient to impart to the blend a temperature within the range of from 0 to -100C.
-allowing the blend to stand till its clarification;
-filtration of the blend clarified upon settling;
15. A compositon according th Claim 1, subatantially as described in the Specification and Examples hereinbefore.
16. A process for producing a compositonaccording to
Claim 2, substantially as described in the Specification and Examples hereinbefore.
17. An alcoholic beverage according to claim 13, substantially as described in the specification and
Examples hereinbefore.
18. A process for producing an alcoholic beverage according to claim 14, substantially as described in the specification and Examples hereinbefore.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB868628228A GB8628228D0 (en) | 1986-11-26 | 1986-11-26 | Composition inhibiting pathological addiction to alcohol |
Publications (3)
Publication Number | Publication Date |
---|---|
GB8706977D0 GB8706977D0 (en) | 1987-04-29 |
GB2198041A true GB2198041A (en) | 1988-06-08 |
GB2198041B GB2198041B (en) | 1991-06-05 |
Family
ID=10607953
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB868628228A Pending GB8628228D0 (en) | 1986-11-26 | 1986-11-26 | Composition inhibiting pathological addiction to alcohol |
GB8706977A Expired - Fee Related GB2198041B (en) | 1986-11-26 | 1987-03-24 | Composition inhibiting pathological addiction to alcohol |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB868628228A Pending GB8628228D0 (en) | 1986-11-26 | 1986-11-26 | Composition inhibiting pathological addiction to alcohol |
Country Status (4)
Country | Link |
---|---|
DE (1) | DE3641495A1 (en) |
FR (1) | FR2607391B1 (en) |
GB (2) | GB8628228D0 (en) |
SE (1) | SE459841B (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5559152A (en) * | 1992-07-06 | 1996-09-24 | Komissarova; Irina A. | Pharmaceutical composition having antiacoholic activity |
WO1999027801A1 (en) * | 1997-11-27 | 1999-06-10 | Tagg Npd Limited | Revitalisation formulation |
WO2002034277A1 (en) * | 2000-10-23 | 2002-05-02 | Council Of Scientific And Industrial Research | Pharmaceutical composition comprising wikstromol and/or matairesinol, its use as hepatoprotectant and process for their isolation from cedrus deodara |
WO2003011279A1 (en) * | 2001-07-27 | 2003-02-13 | Council Of Scientific And Industrial Research | (-)-olivil as antioxidant |
US7211567B1 (en) | 1999-03-26 | 2007-05-01 | Sunstar, Inc. | Composition for preventing and treating type I allergy |
JP2019097563A (en) * | 2017-12-04 | 2019-06-24 | 花王株式会社 | Beverage composition |
US10918654B1 (en) | 2019-09-23 | 2021-02-16 | Alps Pharmaceutical Ind. Co., Ltd. | Rutin compositions |
US11110109B2 (en) | 2019-10-22 | 2021-09-07 | Alps Pharmaceutical Ind. Co., Ltd. | Water soluble O-glycosyl flavonoid compositions and methods for preparing same |
US11266671B2 (en) | 2018-04-23 | 2022-03-08 | Alps Pharmaceutical Ind. Co., Ltd. | Compositions of O-glycosyl flavonoids |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4415087A1 (en) * | 1994-04-29 | 1995-11-09 | Zschiegner Hans Joachim Dr | Lignin based compsn. for use in balneotherapy, cosmetics etc |
US5798371A (en) * | 1995-01-13 | 1998-08-25 | Komissarova; Irina Alexeevna | Pharmaceutical composition endowed with an antialcoholic and nootropic effect |
US6689809B2 (en) | 1999-03-30 | 2004-02-10 | Hormos Nutraceutical Oy Ltd. | Food additive or product or a pharmaceutical preparation, comprising hydroxymatairesinol |
US6451849B1 (en) * | 1999-03-30 | 2002-09-17 | Hormos Nutraceutical Oy Ltd. | Use of hydroxymatairesinol for prevention of cancers, non-cancer, hormone dependent diseases and cardiovascular diseases by hydroxymatairesinol, and a pharmaceutical preparation, food additive and food product comprising hydroxymatairesinol |
DE102006008772A1 (en) * | 2006-02-22 | 2007-08-23 | Beiersdorf Ag | Use of hydroxymatairesinol to prepare cosmetic or dermatological formulation for the protection of sensitive and dry skin, and to increase cerium amide biosynthesis and strengthen the barrier function of the skin |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2184550A1 (en) * | 1972-05-17 | 1973-12-28 | Biolog Appliq Ee Sarl | Leucoanthocyanin extract of fresh cypress cones - with capillary protective activity |
FR2274313A2 (en) * | 1973-07-20 | 1976-01-09 | Biologie Appliquee Sarl | Compsn for treating capillary lesions - produced from cypress galls by treatment with methanol and water mixt and further processing |
DE3115348A1 (en) * | 1981-04-15 | 1982-12-02 | Waldemar 8201 Thansau Leonhard | Beverage, containing fructose and vitamin C, for the accelerated reduction of the blood alcohol level, and process for the preparation of the beverage |
-
1986
- 1986-11-26 GB GB868628228A patent/GB8628228D0/en active Pending
- 1986-11-27 SE SE8605090A patent/SE459841B/en not_active IP Right Cessation
- 1986-12-01 FR FR8616754A patent/FR2607391B1/en not_active Expired
- 1986-12-04 DE DE19863641495 patent/DE3641495A1/en active Granted
-
1987
- 1987-03-24 GB GB8706977A patent/GB2198041B/en not_active Expired - Fee Related
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5559152A (en) * | 1992-07-06 | 1996-09-24 | Komissarova; Irina A. | Pharmaceutical composition having antiacoholic activity |
WO1999027801A1 (en) * | 1997-11-27 | 1999-06-10 | Tagg Npd Limited | Revitalisation formulation |
US7211567B1 (en) | 1999-03-26 | 2007-05-01 | Sunstar, Inc. | Composition for preventing and treating type I allergy |
WO2002034277A1 (en) * | 2000-10-23 | 2002-05-02 | Council Of Scientific And Industrial Research | Pharmaceutical composition comprising wikstromol and/or matairesinol, its use as hepatoprotectant and process for their isolation from cedrus deodara |
WO2003011279A1 (en) * | 2001-07-27 | 2003-02-13 | Council Of Scientific And Industrial Research | (-)-olivil as antioxidant |
JP2005505522A (en) * | 2001-07-27 | 2005-02-24 | カウンセル オブ サイエンティフィック アンド インダストリアル リサーチ | (-)-Olivil as an antioxidant |
JP2019097563A (en) * | 2017-12-04 | 2019-06-24 | 花王株式会社 | Beverage composition |
US11266671B2 (en) | 2018-04-23 | 2022-03-08 | Alps Pharmaceutical Ind. Co., Ltd. | Compositions of O-glycosyl flavonoids |
US10918654B1 (en) | 2019-09-23 | 2021-02-16 | Alps Pharmaceutical Ind. Co., Ltd. | Rutin compositions |
US11110109B2 (en) | 2019-10-22 | 2021-09-07 | Alps Pharmaceutical Ind. Co., Ltd. | Water soluble O-glycosyl flavonoid compositions and methods for preparing same |
Also Published As
Publication number | Publication date |
---|---|
SE459841B (en) | 1989-08-14 |
SE8605090D0 (en) | 1986-11-27 |
GB8628228D0 (en) | 1986-12-31 |
GB2198041B (en) | 1991-06-05 |
GB8706977D0 (en) | 1987-04-29 |
SE8605090L (en) | 1988-05-28 |
FR2607391B1 (en) | 1989-03-31 |
DE3641495A1 (en) | 1988-06-09 |
FR2607391A1 (en) | 1988-06-03 |
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