Food product for use in the prevention and treatment of alcohol- induced hangovers

Abstract

A food composition capable of suppressing the negative effects of the blood alcohol level, lowering the alcohol level in the blood by promoting its metabolism.

Description

[0001] Title : FOOD PRODUCT FOR USE IN THE PREVENTION AND TREATMENT

[0002] OF ALCOHOL- INDUCED HANGOVERS

[0003] DESCRIPTION

[0004] This patent application pertains to a food composition capable of suppressing the negative ef fects of the blood alcohol level , lowering the alcohol level in the blood by promoting its metabol ism .

[0005] FIELD OF APPLICATION

[0006] The found subj ect of thi s patent application is applicable in the field of producing food compositions , particularly liquid food compositions , speci fically in the sector of producing liquid food compositions as dietary supplements for use in preventing and treating the afteref fects of excessive alcohol consumption .

[0007] Excessive consumption of alcoholic beverages is known to cause a condi t ion of discomf ort— commonl y referred to a s a "hangover"-- characteri zed by dehydration, headache , hypoglycemia, due to the persistence of alcohol in the blood . This condition arises from the intake of an alcohol quantity that surpasses the body ' s metabol ic capacity .

[0008] It ' s also known that in the human body, ethanol is metaboli zed to acetaldehyde and from acetaldehyde to acetate through an enzyme - alcohol dehydrogenase (ALDH) - predominantly found in hepatic mitochondria . Primarily, the conversion of ethanol to acetaldehyde and then from acetaldehyde to acetate occurs in the liver . Acetate is released into the bloodstream from the liver and then trans ferred to tissues .

[0009] Both acetaldehyde and acetate present a high degree of toxicity to the human body and constitute the main cause of discomfort due to excessive alcohol intake .

[0010] The human body possesses endogenous detoxi fication mechanisms that activate chemical reactions catalyzed by heme enzyme enzymes , acting on va rious endogenous or exogenous substrates such as drugs and toxins . Consequent ly, excessive ethanol consumption leads to an increase in the production of reactive oxygen species (ROS; like hydroxyethyl radical, superoxide anion, and hydroxyl radical, rendering the action of these endogenous detoxification mechanisms insufficient, particularly the oxidative metabolism of monooxygenases involving cytochrome p Zj 5 Q

[0011] Chemical species such as the superoxide anion react with nitric oxide, reducing its availability and generating peroxynitrite, a reactive nitrogen species (RNS) capable of damaging key macromolecules. The increase in circulating ROS is also favored by excessive mobilization of free iron by ferritin through the Fenton reaction. Alcohol abuse results in a reduction of endogenous antioxidant defenses, lowering the concentrations of retinol, a-tocopherol, and glutathione. Vitamin E deficiency increases lipid peroxidation (LPO) , leading to increased production of malondialdehyde (MDA) [9] . Vitamin A deficiency contributes to lysosomal damage, while decreased glutathione content leads to mitochondrial dysfunction and increased susceptibility of cells to apoptosis State of the art

[0012] The physiological time for reducing the alcohol level in the human body is dependent on the alcohol concentration itself. For instance, 12 grams of alcohol are metabolized within a variable timeframe, ranging between two to three hours, based on factors such as the individual's weight, gender, dietary conditions (full or empty stomach) , and liver condition.

[0013] At the current state of the art, various products are known to be on the market, purporting to lower / control blood alcohol1. G V G1. S .

[0014] A first set of products consists of plant extracts containing polyphenols, purportedly aiming to increase the activity of antioxidant enzymes like superoxide dismutase and reduce c i r cul a L mg MJJA.. For instance, preparations are known in the state of the art containing a mixture of silybin, silicristin, and silidianin in ratios of 3:1:1, known as Silymarin, supplemented with other components that appear to have an immediate detoxifying action, reducing the alcohol content in the blood in the short term.

[0015] The compound myricetin, extracted from Myrica cerifera and tested on mice, also exhibits significant effects on reducing alcohol in the bloodstream by activating ADH to break down circulating alcohol [131. Recently, sodium pyrroloquinoline quinone has been authorized as a novel food by EFSA. In animal models, it promotes the activity of ADH, catalase, and superoxide dismutase, reducing oxidative stress

[0014] , Some researchers conducted a study on the effects of red wine intake on blood alcohol levels

[0015] . The results are controversial because the higher blood alcohol levels in women compared to men might be due to differences in body composition and gender- related variations. Gastric ADH activity is reduced in women, which could contribute to this difference in blood alcohol levels between the sexes.

[0016] An example of an already known food supplement in the state of the art is mentioned in the patent application EP3700358, describing and claiming the development of an energizing; food supplement containing creatine, taurine, caffeine, Withania somnifera extract, silybum marianum extract, willow extract, vitamin B12, vitamin B6, vitamin Bl, fructose, and any excipients. According to the mentioned document, the described finding finds application in preventing and treating the aftereffects of alcohol intoxication - hangovers.

[0017] In particular, according to the aforementioned document:

[0018] • Creatine promotes ATP formation, helping to counteract the feeling of fatigue caused by alcohol intoxication.

[0019] • Taurine stimulates water intake into cells, counteracting the effects of dehydration due to alcohol intoxication and promoting bile acid synthesis. • Caffeine acts on the central nervous system and the cardiovascular system, leading to increased alertness and wakefulness .

[0020] • Withania somnifera root extract acts as a neuroprotective agent, counteracting the effects of alcohol and acetaldehyde on the central nervous system.

[0021] • Silybum marianum extract works on the digestive function with a purifying and antioxidant action. Specifically, the silymarin— a complex of bioflavonoids within the extract- acts as a defense against various intoxicating substances, including alcohol.

[0022] • Willow extract has an anti-inflammatory function.

[0023] • B-group vitamins serve as activators of metabolism.

[0024] The known solutions described are potentially effective in mitigating the undesired effects of alcohol intoxication; however, they do not intervene in reducing the concentration of alcohol present in the blood.

[0025] Patent US2019298684 describes a composition to reduce or mitigate the negative effects resulting from the consumption of alcoholic beverages. This composition includes dihydromyricetin C15H12O, a source of free-form silymarin, and pyrroloquinoi ine quinone. However, the free-form silymarin, despite its known positive effects, appears to be inefficiently assimilated by the body, resulting in a loss of effectiveness of the composition. The purpose of the present patent application is to create a food composition for use in preventing and treating the aftereffects of intoxication, where said composition acts on the alcohol concentration in the blood.

[0026] The further purpose of the invention described in this patent application is to create a discovery that can decrease the concentration of alcohol in the blood within a timeframe shorter than the physiologically necessary time, which, in an average individual, typically takes about 2-3 hours. Another purpose of the invention subject to this patent application is to create a dietary composition for the prevention and treatment of hangover symptoms, said composition aiming to have effects in reducing oxidative stress.

[0027] Summary of the invention

[0028] The subject matter of this patent application is a food product comprising a complex of Silybum Marianum and phospholipids, hereinafter referred to as 'silymarin phytosome, ' sodium salt of pyrroloquinoline quinone, and 3, 5, 7-Trihydroxy-2 (3,4,5 — trihydroxyphenyl) -4-chromenone, hereinafter referred to as 'myricetin. This product is preferably, but not exclusively, in an aqueous solution.

[0029] Detailed description

[0030] The invention subject to this patent application consists of a food preparation, referred to as such, comprising flavonoids and peptides in an aqueous solution.

[0031] Specifically, the food preparation subject to this patent application includes:

[0032] Flavonoids: silymarin phytosome, myricetin,

[0033] Peptides: sodium salt of pyrroloquinoline; said preparation being able to act on alcohol levels and oxidative stress markers caused by alcohol intake.

[0034] In particular, the invention subject to this patent application consists of a liquid food preparation.

[0035] In an exemplary embodiment, the liquid composition of the product subject to this patent application consists of silymarin phytosome in a percentage ranging from 0.203 to 0.30%, sodium salt of pyrroloquinoline quinone in a percentage ranging from 0.03% to 0.10%, myricetin in a percentage ranging from 0.50% to 0.80%, H2O in a percentage ranging from 60% to 75%, and components commonly known in the relevant field for formulating liquid food products in a percentage ranging from 25% to 40%.

[0036] The commonly known components in the relevant field for formulating liquid food products can include, by way of example and not limitation, fructose, citric acid, flavors, potassium sorbate, and sodium benzoate.

[0037] In an exemplary embodiment, the solid composition of the product subject to this patent application consists of silymarin phytosome in a percentage ranging from 10% to 15%, sodium salt of pyrroloquinoline quinone in a percentage ranging from 2% to 4%, myricetin in a percentage ranging from 30% to 40%, and components known for formulating solid food products in a percentage ranging from 41% to 58%.

[0038] The known components for formulating solid food products can consist of N-Acetylcysteine, flavors, glyceryl monobehenate, silica, sucralose.

[0039] Experimental Results

[0040] The study on the effects of the food product subject to this patent application was conducted through a randomized, controlled, single-blinded trial. The effects of consuming a product based on silymarin phytosome, sodium salt of pyrroloquinoline quinone, and myricetin on alcohol levels and oxidative stress markers were measured in subjects consuming red wine, both on day 0 (acute intake) and after 7 days of treatment. The invention subject to this patent application was administered to subjects aged between 18 and 35 years old, without any history or current habits of alcohol or substance abuse / dependence, of Caucasian race and ethnicity, and without autoimmune, endocrine, infectious, cardiac, renal, hepatic, or metabolic diseases. Subjects who had taken medications in the seven days prior to the experiment and pregnant or lactating women were excluded.

[0041] For study eligibility, blood tests were conducted to assess: complete blood count (CBC) , liver function (AST, ALT, GGT, total and fractionated bilirubin) .

[0042] After eligibility and inclusion, the subjects were randomized using an electronic number generator into the following two groups by personnel not involved in the experiment: A) Administration of placebo (sham-control) ;

[0043] B) Administration of the product subject to this patent appl icatio .

[0044] During the week before the experiment, subjects abstained from consuming alcoholic beverages, and during the experiment, they only consumed the products as instructed and in the specified doses. In the 12 hours prior to the test, subjects refrained from consuming caffeine.

[0045] The alcoholic beverage administered consisted of a quantity of 150 ml of Cabernet red wine (alcohol content: 12.5-13%; alcohol content per serving: 14.81 - 15.40 g, corresponding to the average drink size as indicated by Kerr et al.) throughout the duration of the experiment and for ail subjects.

[0046] Before commencing the experimentation, blood samples, saliva, and urine were collected to obtain pre-treatment samples (TO) . On day 1 of the experiment, in order to obtain data on acute intake, eligible subjects underwent blood sampling at 60, 120, and 240 minutes after consuming a glass of wine (150ml) to establish the ethanol metabolism curve, after a minimum 4-hour fasting period.

[0047] The placebo or the product subject to this patent application was consumed immediately after drinking the glass of wine. Subjects then continued consumption for a week by drinking, in similar manners, one glass (150 ml; at lunch and one at dinner (total of 300 ml / day, approximately 30g of alcohol / day) of the provided red wine, while taking the prescribed placebo or the product subject to this patent application (according to the randomization group) .

[0048] The subjects were asked to have a glass of wine at the beginning of their meal, followed by consuming a balanced daily menu tailored to their individual energy needs. On day 7, the same series of samples were taken following the same procedures as described on day 0, and then the experimentation was concluded. None of the subjects were aware of their assignment to the placebo or the product under this patent application. Analyzed parameters include : » Blood alcohol concentration

[0049] • Ethyl glucuronide (EtG) in urine

[0050] • Quantification of reactive oxygen species (ROS) production and total antioxidant capacity (TAC) using electron paramagnetic resonance spectroscopy (EPR) .

[0051] • Assessment of oxidative damage to proteins, lipids, and DNA through immuno-enzymatic assays: Protein Carbonyls (PC) , 8-iso- Prostaglandin F2oc (8-iso-PGF2oc) , and 8-Hydroxy-2 ’ - deoxyguanosine (8-OH-dG) .

[0052] • Quantification of nitric oxide (NO) through nitric oxide metabolites (NOx) and inducible nitric oxide synthase (iNOS) using ELISA tests.sMeasurement of polyphenols and / or ascorbic acid through colorimetric tests and / or ELISA and / or EPR.

[0053] • Reduced and total aminothiols (cysteine, cysteinylglycine, homocysteine, glutathione) will be measured in RBC (red blood cells) and / or plasma using HPLC .

[0054] • Uric acid, neopterin, and creatinine will be assessed using

[0055] After applying the Kolmogorov-Smirnov test to verify the normality of the distribution, a one-way ANOVA and t-test were used to compare the trend of values between the two groups. The significance level was set at <0.05.

[0056] Results

[0057] A total of 20 subjects were included (7 female) , with an average age of 29 years and no significant alterations in the screening par ame t er s .

[0058] Effects of acute intake on blood alcohol concentration

[0059] The histogram in Table 1 shows that the blood alcohol concentration at day 1, 120 minutes after intake, is over 33% higher in those who took the placebo compared to those who took the product subis i s p a t e n t app 1 i cat

[0060] Table 3 and subsequent tables using the term "product".

[0061] The histogram in Table 2 displays the value of ethyl glucuronide (EtG) , a metabolic product of ethanol formed in the body through conjugation of ethanol with glucuronic acid, measured on day 1 at 120 minutes after intake. A statistically significant difference (p<0.01) is evident between pre and post Intake in both groups (product subject to patent application vs. Placebo) . There isn't a significant difference between the two post” values, which could be influenced by metabolism. Any samples taken 4 hours post-intake should be considered.

[0062] Effect of intake on acute and chronic oxidative stress On the 1st day of administration, the analysis of Reactive Oxygen Species (ROS) using the ERR technique on Plasma samples did not show differences in the placebo group. On the contrary, significant differences (p<0.05) after product administration were highlighted between TO and Tl; Tl and T3.

[0063] Although not significant, the percentage difference between the product subject to the patent application and the placebo is noteworthy: a +5% in the placebo at Tl and +16.5% at T3 (Table 3) . The lack of significance is attributable to the sample size. On the 7th day after intake, no differences are observed between the baseline (TO of the product subject to the patent application vs placebo) in ROS. Table 4 shows significant differences (p<0.05) in the product on the 7th day between TO and Tl, T2, and T3. Significant differences in the placebo between TO and Tl, T2, and T3.

[0064] On the 1st day of administration, the analysis of Total Antioxidant Capacity (TAG) using the EPR technique on Plasma samples showed the following statistically significant differences (p<0.05) : the product subject to this patent application at TO vs T3 and in the placebo between TO and T2, and T3 (Table 5) . On the 7th day of administration, the analysis of Total Antioxidant Capacity (TAC) using the ERR technique on Plasma samples showed the following statistically significant differences (p<0.05) : the product subject to this patent application at TO vs T3 (+15%) and between the product subject to the patent application vs placebo at T3 (+13%) (Table 6) . .analyses of Q10 asj.ng vrT.id vi able / , does not show sta Li i-i-caliy significant differences, probably due to the standard deviation of the sample and therefore the sample size.

[0065] Subsequently, analyses were conducted using saliva samples. The markers of Total Antioxidant Capacity (Table 8.1 - 8.2) and Reactive Ozygen Species (ROS) (Table 9.1 - 9.2) were monitored for 7 days using the EPR technique with saliva samples. The kinetics of the product subject to this patent application are shown in Table 8.1 and 9.1, while those of the placebo are in

[0066] Interesting is the different response between the 1st and 7th day of the two substances, where there is a greater and pers stent increase in Total Antioxidant Capacity (TAG) in the kinetics of the product subject to the patent application. The response of Reactive Ozygen Species (ROS) is opposite, another aspect of the oxidative stress balance.

[0067] The redox state, namely the analysis of amino thiols, was quantified from RBC (Red Blood Cells) using HPLC.

[0068] No difference in total GSH (Glutathione) between the product subject to the patent application and the placebo (Table 10.1 - 10.2 - 10.3) . However, a significant modification (p<0.05) is observed in reduced GSH between the baselines of day 1 and day 7 in the group using the product under this patent application, with a shift to the oxidized state on the 7th day.

[0069] Total cysteine (Cys) remains unchanged on the 1st day, while a significant difference (p<0.05) is observed on the 7th day after the administration of the product under this patent application (Table 11.1 -• 11,2) . This could be due to the change in oxidized GSH, which decreases at the same time. There is no statistical difference between the two groups for the other examined amino thiols, such as cysteinylglycine and homocysteine, in their three forms: total, oxidized, and reduced.

[0070] Subsequently, analyses were conducted using urine samples to assess lipid peroxidation, uric acid, and neopterin (Table 12.1 - 12.2 - 12.3) From the data, it is evident that:

[0071] The histogram shows an increasing trend in uric acid at 7 days (+35%) after intake of the product subject to this patent application. This data strengthens the statistical significance of Total Antioxidant Capacity (TAG) , supporting the concept of the antioxidant power of the product under this patent application. (Table 12B) .

[0072] No change is measured in neopterin in either group. (Table 120) .

[0073] The data, however, align with the literature; indeed, it is known that the primary exogenous sources of free radicals include alcohol, smoking, and pollution. As evident from the graphs, with the increase in blood alcohol levels (Table 1 and 2) , there is also an increase in Reactive Oxygen Species (ROS) production (Table 3, 4, and 9) . These ROS, in turn, have multiple effects; they are capable of promoting the expression of genes that synthesize molecules with antioxidant action, and therefore, they can act as signaling molecules (Table 4, 5, and 8 '

Claims

1. Detoxification product for human use to prevent and recover from detrimental effects of alcohol consumption, said detoxification product comprising a complex of silymarin, pyrroloquinoline quinone sodium salt, said complex being characterized in that the silymarin is silymarin phytosome and in that it comprises myricetin Ci H10O6and one or more excipients in a physiologically acceptable carrier.

2. Detoxification product as per claim 1 characterized in that the physiologically acceptable carrier is water.

3. Detoxification product as per claim 1, 2 characterized in that the composition includes phytosome silymarin in percentage between 0,20% and 0,30%.

4. Detoxification product as per claim 1, 2, 3 characterized in that the composition includes pyrroloquinoline quinone sodium salt in percentage between 0,03% and 0, 10%.

5. Detoxification product as per claim 1, 2, 3, 4 characterized in that the composition includes myricetin in percentage between 0 , 50 % and 0 , 80%.

6. Detoxification product as per claim 1, characterized in that the physiologically acceptable carrier is solid.

7. Detoxification product as per claim 1 characterized in that the composition includes phytosome silymarin solution in percentage between 10% and 15%.

8. Detoxification product as per claim 7 characterized in that the composition includes pyrroloquinoline quinone sodium salt in percentage between 2% and 4%.

9. Detoxification product as per claim 7, 8 wherein the composition includes myricetin solution in percentage between30 % and 40%.

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