JP7526363B2 - Drug composition for treating or reducing alcohol hangover and its use - Google Patents

Description

The present invention relates to a novel drug composition for treating or reducing alcohol hangover, liver, kidney and gastrointestinal damage.

Alcohol hangover is the most commonly reported adverse effect of excessive drinking and appears when the blood alcohol concentration (BAC) returns to near zero. Ethanol is miscible with water, so it targets water-rich tissues, e.g., the brain, causing familiar symptoms such as general distress, headache, fatigue, attention problems, dry mouth, dizziness, nausea, cognitive impairment, and mood changes. Alcohol hangovers can cause absenteeism, poor performance, reduced productivity, and poor academic performance at work, and can jeopardize potentially dangerous daily activities such as driving a car or operating heavy machinery. Compared to common diseases and other health risk factors, these socioeconomic consequences and health risks of alcohol hangovers are much higher.

The search for treatments for alcohol-related damage and side effects (including hangovers) is as old as alcohol itself. Many treatments and preventative medications are available, but scientific evidence of their effectiveness is generally lacking.

Thus, there is a need for methods and compositions that rapidly reduce the symptoms of elevated blood alcohol concentration (BAC), or rapidly restore wakefulness after drinking alcohol, or reduce or prevent the symptoms of drinking alcohol. The present invention addresses this and other needs.

[Problem to be solved by the invention]
[Means for solving the problems]
In one embodiment, the present invention discloses a pharmaceutical composition comprising (1) an herbal mixture including at least two herbs selected from the group consisting of Dried Ginger, Doujinshi, Poria Coccus, Unshiu Citrus Peel, and Atractylodes Rhizome; and (2) a pharmaceutically acceptable carrier.

In another embodiment, a pharmaceutical composition is provided that includes (1) a mixture of herbs including Doujinshi, Poria Coccinea, and Citrus Unshiu Peel, and (2) a pharmaceutical acceptable carrier.

In another embodiment, a pharmaceutical composition is provided that includes (1) a mixture of herbs including dried ginger, dojin, bukkake, citrus unshiu peel, and byaku-atracto, and (2) a pharmaceutically acceptable carrier.

Further included is the use of the drug compositions described herein for the manufacture of a drug for treating or reducing the effects of alcohol consumption.

Further included are uses in which the drug compositions described herein are used to manufacture drugs for treating or reducing hepatocellular inflammatory effects and fat accumulation.

Further included are uses in which the drug compositions described herein are used to manufacture a drug for treating or reducing small intestinal mucosa or intestinal dysfunction.

Further included are uses in which the drug compositions described herein are used to manufacture a drug for treating or reducing glomerular damage or impaired renal function.

Further provided are methods for treating or reducing the effects of alcohol consumption in an individual in need thereof by administering a drug composition described herein.

The terms "invention" and "present invention" as used in this patent are intended to broadly refer to all subject matter of this patent and the following claims. Statements containing these terms should be understood as not limiting the subject matter described herein or the meaning or scope of the following claims. The embodiments of the invention contained in this patent are defined by the following claims, not the contents of the invention. The contents of the invention are a high level summary of various aspects of the invention and illustrate some concepts that are further described in the embodiments section below. The contents of the invention are not intended to determine key features or essential characteristics of the claimed subject matter, nor are they intended to be used alone to determine the scope of the claimed subject matter. The subject matter should be understood by reference to appropriate portions of the entire specification, any or all drawings, and the scope of each claim.

The present invention will become clearer with reference to the following drawings and embodiments.

1 is a line graph illustrating the effect of the pharmaceutical composition of the present invention on mouse body weight. 1 is a histogram illustrating the effect of a pharmaceutical composition of the present invention on the liver/body weight ratio and kidney/body weight ratio in mice. 1 is a histogram illustrating the effect of a pharmaceutical composition of the present invention on the liver/body weight ratio and kidney/body weight ratio in mice. 1 is a histogram illustrating the effect of the pharmaceutical composition of the present invention on serum liver function (AST and ALT) levels in mice. 1 is a histogram illustrating the effect of the pharmaceutical composition of the present invention on serum liver function (AST and ALT) levels in mice. 1 is a histogram illustrating the effect of a pharmaceutical composition of the present invention on serum total cholesterol (T-CHO) and triglyceride (TG) levels in mice. 1 is a histogram illustrating the effect of a pharmaceutical composition of the present invention on serum total cholesterol (T-CHO) and triglyceride (TG) levels in mice. 1 is a histogram illustrating the effect of a pharmaceutical composition of the present invention on serum glucose levels in mice. 1 is a histogram illustrating the effect of a pharmaceutical composition of the present invention on total cholesterol (T-CHO) and triglyceride (TG) levels in the liver of mice. 1 is a histogram illustrating the effect of a pharmaceutical composition of the present invention on total cholesterol (T-CHO) and triglyceride (TG) levels in the liver of mice. 1 is a histogram illustrating steatosis evaluation when the pharmaceutical composition of the present invention treats mice with alcoholic liver disease. 1 is a histogram illustrating the effect of an embodiment of a drug composition of the present invention on performance in a Field Vigilance Test. 1 is a histogram illustrating the effect of one embodiment of a pharmaceutical composition of the present invention on alcohol-related symptoms one hour after drinking. 1 is a histogram illustrating the effect of one embodiment of a pharmaceutical composition of the present invention on alcohol-related symptoms two hours after drinking. 1 is a histogram illustrating the effect of one embodiment of a pharmaceutical composition of the present invention on alcohol-related symptoms 24 hours after consumption. 1 is a histogram illustrating the effect of one embodiment of the pharmaceutical composition of the present invention on liver function tests (AST, ALT and γ-GT). 1 is a histogram illustrating the effect of one embodiment of the pharmaceutical composition of the present invention on liver function tests (AST, ALT and γ-GT). 1 is a histogram illustrating the effect of one embodiment of the pharmaceutical composition of the present invention on liver function tests (AST, ALT and γ-GT). 1 is a histogram illustrating the effect of one embodiment of a pharmaceutical composition of the present invention on renal function tests (aldosterone and creatinine). 1 is a histogram illustrating the effect of one embodiment of a pharmaceutical composition of the present invention on renal function tests (aldosterone and creatinine). 1 is a histogram illustrating the effect of one embodiment of a pharmaceutical composition of the present invention on glucose-6-phosphate dehydrogenase (G6PD). A collection of hematoxylin and eosin stained (H and E) images showing alcohol-induced damage to the jejunal villi (Figure B) and that one embodiment of the drug composition of the present invention reduces alcohol-induced damage to the small intestinal capsule (Figures C-E). A collection of H and E images showing alcohol-induced glomerular damage (Figure B) and that one embodiment of the drug composition of the present invention reduces alcohol-induced glomerular damage (Figures C-E).

DEFINITIONS As used above and throughout the content of this disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

As used herein, the singular terms "a/an" and "the" include plural referents unless the context clearly dictates otherwise.

As used herein, "effective amount" includes a dose of a drug composition sufficient to treat or ameliorate at least one symptom resulting from alcohol consumption or elevated BAC.

As used herein, the term "treatment" means the palliative use or effect and/or the delaying or suppression of the onset of symptoms or signs due to alcohol.

As used herein, the term "individual" generally refers to a human or animal having or suspected of having a condition attributable to alcohol consumption or elevated BAC. That is, an individual who has consumed alcohol is included within the scope of the term "individual" regardless of whether or not they have symptoms or signs of alcohol consumption or elevated BAC.

All numbers herein may be understood to be modified by "about." As used herein, the term "about" is meant to encompass a variation of ±10%.

In one embodiment, the present invention discloses a pharmaceutical composition comprising (1) an herbal mixture containing at least two herbs selected from the group consisting of dried ginger, doujin, poria chebula, unripe citrus fruit, and byaku-atracto, and (2) a pharmaceutically acceptable carrier.

In one exemplary embodiment, the herbal mixture includes dried ginger and pearl ginseng. In one exemplary embodiment, the herbal mixture includes pearl ginseng and Poria columbine. In one exemplary embodiment, the herbal mixture includes Poria columbine and Unripe Citrus Peel. In one exemplary embodiment, the herbal mixture includes Unripe Citrus Peel and Byathria Root. In one exemplary embodiment, the herbal mixture includes dried ginger and Poria columbine. In one exemplary embodiment, the herbal mixture includes dried ginger and Unripe Citrus Peel. In one exemplary embodiment, the herbal mixture includes dried ginger and Unripe Citrus Peel. In one exemplary embodiment, the herbal mixture includes Pearl ginseng and Unripe Citrus Peel. In one exemplary embodiment, the herbal mixture includes Pearl ginseng and Byathria Root. In one exemplary embodiment, the herbal mixture includes Poria columbine and Unripe Citrus Peel.

In another embodiment, the present invention discloses a pharmaceutical composition comprising (1) an herbal mixture containing at least three herbs selected from the group consisting of Dried Ginger, Doujinshi, Poria Coccinea, Uncaria Citrifolia, and Byak Atractylodes Root, and (2) a pharmaceutically acceptable carrier.

In one exemplary embodiment, the herbal mixture includes dried ginger, pearl ginseng, and Poria columbine. In one exemplary embodiment, the herbal mixture includes pearl ginseng, Poria columbine, and Unripe Citrus Peel. In one exemplary embodiment, the herbal mixture includes Poria columbine, Unripe Citrus Peel, and Baia Atractylodes Rhizome. In one exemplary embodiment, the herbal mixture includes Unripe Citrus Peel, Baia Atractylodes Rhizome, and dried ginger. In one exemplary embodiment, the herbal mixture includes dried ginger, pearl ginseng, and Unripe Citrus Peel. In one exemplary embodiment, the herbal mixture includes dried ginger, pearl ginseng, and Unripe Citrus Peel. In one exemplary embodiment, the herbal mixture includes dried ginger, Pearl ginseng, and Baia Atractylodes Rhizome. In one exemplary embodiment, the weight ratio of Pearl ginseng, Unripe Citrus Peel, and Poria columbine in the herbal mixture is about 25-35%:25-35%:30-50%.

In one exemplary embodiment, the herbal mixture includes dried ginger, dojin and byaku-atract. In one exemplary embodiment, the herbal mixture includes dried ginger, poria cocos and byaku-atract.

In one exemplary embodiment, the herbal mixture includes Pearl Ginseng, Unripe Citrus Fruit, and Byaedioic Acid Root. In one exemplary embodiment, the herbal mixture includes Pearl Ginseng, Poria Coccinea, and Byaedioic Acid Root.

In another embodiment, the present invention discloses a pharmaceutical composition comprising (1) a mixture of herbs including Dried Ginger, Doujinshi, Poria Coccus, Unshiu Citrus Peel, and Byak Atractylodes Root, and (2) a pharmaceutically acceptable carrier.

In one exemplary embodiment, the herbal extract comprises about 5-15% dried ginger by weight. In one exemplary embodiment, the herbal extract comprises about 15-25% doujin by weight. In one exemplary embodiment, the herbal extract comprises about 25-35% poria cocos by weight. In one exemplary embodiment, the herbal extract comprises about 15-25% citrus unshiu peel by weight. In one exemplary embodiment, the herbal extract comprises about 10-20% by weight Atractylodes rhizome. In one exemplary embodiment, the herbal extract comprises about 20-25% doujin by weight, about 30-35% poria cocos by weight, about 20-25% citrus unshiu peel by weight, about 15-18% citrus unshiu peel by weight, and about 6-12% dried ginger by weight.

In one exemplary embodiment, the herbal mixture is a dried or freeze-dried powder of at least two of the listed herbs (i.e., Dried Ginger, Doujinshi, Poria Columbine, Unripe Orange Peel, and Byak Atractylodes Rhizome). In one exemplary embodiment, the herbal mixture is a water or alcohol extract of at least two of the listed herbs (i.e., Dried Ginger, Doujinshi, Poria Columbine, Unripe Orange Peel, and Byak Atractylodes Rhizome).

The herbs in the herbal mixture can be fresh herbs, dried powders of fresh herbs, freeze-dried powders, ground powders, decoctions, water or alcohol crude extracts or extract particles. In one exemplary embodiment, the herbal mixture is produced by aqueous extraction, where fresh herbs (optionally ground prior to extraction for optimal extraction results) are heated in water or a solvent, then filtered and concentrated (the liquid extract is concentrated by vacuum or low pressure concentration).

The National Institute on Alcohol Abuse and Alcoholism lists various degrees of impairment associated with increased blood alcohol concentration (BAC):

Mild impairment (BAC between 0.0-0.05%): Mild impairment of speech, memory, attention, coordination, balance, impaired relaxation and lethargy.

Moderate impairment (BAC level between 0.06-0.15%): Increased risk of aggression, further impairment of language, memory, attention, coordination, balance and driving skills.

Severe impairment (BAC level between 0.16-0.30%): Severe impairment of speech, memory, attention, coordination, balance, judgment, or decision-making; confusion, fainting, nausea and vomiting, loss of consciousness, mood changes, irregular breathing.

Potentially life-threatening conditions (alcohol overdose, BAC 0.31-0.45%): confusion, loss of consciousness, seizures and extreme hypothermia.

A hangover is a set of symptoms that result from drinking too much alcohol. Typical symptoms include fatigue, weakness, dry mouth, headache, muscle pain, nausea, stomach pain, dizziness, sensitivity to light and sound, anxiety, irritability, sweating, and elevated blood pressure.

For example, it may be desirable to administer the drug composition before, during, or immediately after socially drinking any amount of alcohol to reduce symptoms and signs of elevated BAC and to allow the drinker to wake up quickly. It may also be desirable to administer the drug composition to treat and prevent damage to the gastrointestinal and urinary systems, such as damage to the liver, kidneys, or intestines.

The present invention provides a method for treating or reducing the effects of alcohol consumption in an individual in need thereof by administering a drug composition described herein.

Non-limiting examples of effects of drinking alcohol include symptoms, signs, or an alcohol hangover of elevated blood alcohol concentration.

A pharmaceutical composition is amenable to preparation or manufacture with the herbal mixture and a pharma- ceutically acceptable carrier. The pharma-ceutically acceptable carrier may contain, for example, a physiologically acceptable compound for stabilizing or increasing or decreasing the absorption or clearance of the pharmaceutical composition of the present invention. The physiologically acceptable compound may include, for example, carbohydrates such as glucose, sucrose, or polydextrose, antioxidants such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, detergents, liposomal carriers, or other stabilizers and/or buffers. Such formulations may be prepared by a variety of techniques, including combining the herbal mixture with a suitable pharma-ceutically acceptable carrier (e.g., liquid carriers, solid carriers, or both).

The drug compositions provided herein optionally include antioxidants, buffers, bacteriostats, suspending agents, thickening agents, preservatives, cosolvents and tackifiers, or other therapeutic ingredients for treating alcohol disorders, such as acamprosate calcium, gabapentin (brand name NEURONTIN) or topiramate (brand name topamax). Carriers and other therapeutic ingredients must be acceptable in the sense that they are compatible with the drug composition and not harmful to the individual.

The drug composition is administered in an amount effective to reduce a symptom or sign of an elevated BAC in an individual. The dose of the drug composition administered will depend on the amount of alcohol ingested, as well as other clinical factors such as the weight and general condition of the individual, and the route of administration. Useful doses of the drug compositions provided herein are determined by comparing in vitro and in vivo activity in animal models. Methods for extrapolating effective amounts in mice and other animals to humans are known in the art. See, for example, U.S. Pat. No. 4,938,949, incorporated herein by reference.

According to the methods provided herein, the drug composition can be delivered by any of a variety of routes, including, but not limited to, injection (e.g., subcutaneous, intramuscular, intravenous, intraarterial, intraperitoneal, intradermal, intravitreal), dermal, transdermal administration, transdermal absorption, oral (e.g., tablet, powder, pill, buccal, capsule, liquid, edible film, or any suitable dosage form for the herb), implantable osmotic pump, suppository, aerosol spray, topical, ophthalmic, nasal inhalation, pulmonary inhalation, injection into the skin, etc. In one embodiment, the drug composition of the present invention can be administered orally in the form of an aqueous extract.

The drug composition may be administered in a single dose or multiple dose treatments over a period of time. The drug composition may be administered at appropriate intervals, for example, once a day, twice a day, three times a day, four times a day, six times a day, once every other day, once every three days, etc.

The methods described herein also encompass research methods and applications, including in vitro and in vivo methods for treating or reducing the effects of alcohol consumption in an individual after ingesting any amount of alcohol.

Embodiments of the present invention are illustrated by the following examples, which should not be construed as limiting the scope of the invention in any manner. During the work described in the following examples, well-known procedures were followed unless otherwise noted. For illustrative purposes, some procedures are described below.

Example 1: Case study on the effect of pharmaceutical compositions on mice The purpose of this study was to investigate the protective effect of pharmaceutical compositions S1-S11 on improving alcoholic liver damage in a mouse model of alcoholic liver disease, and the components of pharmaceutical compositions S1-S11 are shown in Table 1 below.

1. Alcoholic Liver Disease in Mice Fifty-two 8-week-old C57BL/6 male mice were adapted to a pair-fed liquid diet (control group diet did not contain alcohol) for 1 week, after which the mice were divided into an alcohol-fed group and a pair-fed group (normal control group). The mice in the alcohol-fed group received a Lieber-DeCarli liquid diet (high-fat alcohol liquid diet) daily, with an alcohol concentration of 1-5% (increased by 1-5% daily), and the mice were fed 5% alcohol ad libitum in the liquid diet for 5 weeks. The pair-fed mice served as the normal control group and received a calorie-matched liquid diet (liquid carrier was double distilled water ( _ddH2O )) for 5 weeks.

2. Treatment When the disease induction period begins, mice are treated with carrier ( _ddH2O ) or drug composition orally (PO) once a day (QD) for 35 days or 5 weeks. The dose volume is 12.3 mL/kg (body weight), and the first day of treatment is designated as day 0. The experimental design is shown in Table 2.

Eleven sets of drug compositions, such as S1 to S11, were tested on mice with alcoholic liver disease to evaluate their protective effects against alcoholic liver damage. The first group of animals was pair-fed with a liquid diet, while the normal control group received a carrier ( _ddH2O ). The second group of animals received a Lieber-DeCarli liquid diet, while the disease control group received a carrier (ddH2O). The third to thirteenth groups of animals received the Lieber-DeCarli liquid diet and drug compositions S1 to S11, respectively. Referring to FIG. 1, a significant weight loss was observed in the alcohol-fed mice. No significant weight change was observed in the treatment groups compared to the carrier control group (group 2).

Referring to Figures 2 and 3, at the end of the study (day 34), the average liver/body weight ratio was 5.78%, while the normal control group (Group 1) had a ratio of 3.55% (p<0.05). The average kidney/body weight ratio was 1.35%, while the normal control group (Group 1) had a ratio of 1.01% (p<0.05). As can be seen from this, both the liver/body weight ratio and kidney/body weight ratio were significantly increased in the alcohol-fed mice.

In addition, referring to Figure 2, after treatment of treatment groups S1 (Group 3), S2 (Group 4), S3 (Group 5), S5 (Group 7), S6 (Group 8) or S10 (Group 12), the liver/body weight ratio was significantly decreased compared to the vehicle control group (Group 2) (p<0.05).

3. Serum Chemistry Measurements Mice were fasted overnight before blood sampling on days 0 and 34, and blood samples were collected 4 hours after the last drug administration for serum chemistry analysis. Serum chemistry parameters included AST (aspartate aminotransferase), ALT (alanine aminotransferase), total cholesterol (T-CHO), triglycerides (TG) and blood glucose (GLU), where AST, ALT, CHO and TG were measured using a Hitachi 7180 analyzer and GLU was measured using a glucometer.

Referring to Figures 4 and 5, blood chemistry analysis on day 34 showed a significant increase in serum AST and ALT levels in alcohol-fed mice compared to the normal control group (Group 1), with AST values of 122.5±29.6 U/L compared to 80.8±3.5 U/L in the normal control group (Group 1); ALT values of 49.7±6.3 U/L compared to 33.9±3.0 U/L in the normal control group (Group 1) (p<0.05). However, no significant differences in serum AST and ALT were observed in the treatment groups compared to the vehicle control group (Group 2).

Referring to Figure 6, at the start of treatment (day 0), serum total cholesterol (T-CHO) levels in treatment groups S1 (group 3), S3 (group 5), S5 (group 7), S7 (group 9), or S9 (group 11) were significantly elevated (p<0.05) compared to the vehicle control group (group 2). At the end of the study (day 34), serum T-CHO levels in alcohol-fed mice were significantly elevated (p<0.05) compared to the normal control group (group 1). However, no significant elevation of serum T-CHO was observed in the treatment groups compared to the vehicle control group (group 2).

Referring to Figure 7, serum triglyceride (TG) levels were significantly reduced (p<0.05) in treatment groups S2 (4th group), S3 (5th group), S5 (7th group), S6 (8th group) and S9 (11th group) compared to the carrier control group (2nd group). At the end of the study (day 34), serum TG levels were significantly reduced (p<0.05) in alcohol-fed mice compared to the normal control group (1st group). However, no significant changes in serum TG were observed in the treatment groups compared to the carrier control group (2nd group).

Referring to Figure 8, at the start of treatment (day 0), serum glucose levels in treatment groups S1 (group 3), S2 (group 4), or S5 (group 7) were significantly elevated (p<0.05) compared to the vehicle control group (group 2). However, at the end of the study (day 34), serum glucose levels in alcohol-fed mice were significantly decreased (p<0.05) in treatment group S8 (group 10) compared to the vehicle control group (group 2).

4. Measurement of liver total cholesterol (T-CHO) and triglyceride levels At the end of the study on day 34, liver tissues were harvested and extracted with PBS. Total cholesterol (T-CHO) and triglycerides (TG) in the tissues were analyzed using a Hitachi 7180 analyzer.

Referring to Figures 9 and 10, liver total cholesterol (T-CHO) and triglyceride (TG) levels were increased in alcohol-fed mice. Compared with the carrier control group (Group 2), liver T-CHO levels were significantly decreased (p<0.05) in treatment groups S7 (Group 9), S8 (Group 10), S9 (Group 11) and S11 (Group 13). However, compared with the carrier control group (Group 2), liver TG levels were significantly decreased (p<0.05) in treatment group S8 (Group 10).

5. Measurement of Liver Enzymes The results of measuring the glutathione peroxidase (GPx) level in the liver by the ELISA method are shown in Table 3.

6. Microscopic Evaluation When mice were sacrificed, tissue samples were taken and preserved in 10% neutral buffered formalin (NBF). Livers, kidneys and intestines were trimmed, paraffin-embedded, sectioned and stained with H (hematoxylin) and E (eosin) and examined under a microscope (Leica DM2700M) by a veterinary pathologist blinded to the nature of the treatments.

6.1 Semi-quantitative score of hepatic fatty lesions The severity classification system of microscopic hepatic fatty lesions is shown in Table 4 below, and the post-treatment scores of each group are shown in Table 5 below and FIG.

Referring to FIG. 11, the liver steatosis lesion score was significantly reduced in mice fed the Lieber-DeCarli liquid diet treated with treatment group S5 (group 7) compared to the vehicle control group (group 2) (p<0.05, one-way ANOVA). Therefore, as can be seen from the results, treatment group S5 (group 7) can protect mice from alcohol-induced increased liver steatosis and improve liver pathology in a mouse model of alcoholic liver disease.

6.2 Semi-quantitative scores of histopathological observations According to the reference published in Toxicologic Pathology (Shackelfold et al., 2002), the standard severity classification system for other micro-lesions (liver, kidney, intestine) is shown in Table 6 below, and the post-treatment scores for each group are shown in Table 7 below.

As can be seen from Table 7, minimal mononuclear cell infiltration was observed focally in the liver (2/4 male animals in group 1, 3/4 male animals in group 2, 1/4 male animals in group 4, 3/4 male animals in group 5, 1/4 male animals in group 6, 1/4 male animals in group 7, 3/4 male animals in group 8, 1/4 male animals in group 9, 1/4 male animals in group 10, 2/4 male animals in group 11, 2/4 male animals in group 12, and 2/4 male animals in group 13). The severity of micro-changes was not statistically different between the treatment and vehicle control groups (group 2) (p>0.05, one-way ANOVA).

As can be seen from Table 7, in the kidney, mild chronic progressive renal lesions confined to the cortex (1/4 male animals in group 4), minimal eosinophil proliferation confined to the cortex (1/4 male animals in group 3), minimal eosinophil proliferation confined to the cortex (1/4 male animals in group 5), minimal to mild microtubular type confined to the tubules (1/4 male animals in group 5 and 1/4 male animals in group 7), minimal tubular dilation (1/4 male animals in group 5 and 1/4 male animals in group 9), minimal calcification confined to the papillary tubules (1/4 male animals in group 7). The severity of microalterations was not statistically different between the treatment group and the vehicle control group (group 2) (p>0.05, one-way ANOVA).

As can be seen from Table 7, focal minimal to mild degeneration/necrosis was observed in the intestine (1/4 male animals in group 5 and 1/4 male animals in group 10). The severity of microalterations was not statistically different between the treatment and vehicle control groups (group 2) (p>0.05, one-way ANOVA).

These overall results show that drug composition S5 protects mice from alcohol-induced increased liver steatosis and ameliorates liver pathology in the above mouse model.

7. Statistical Analysis All values are expressed as mean ± standard difference (S.D.) or standard error of the mean (SEM). Unpaired Student's t-test was used for comparison between normal group (Group 1) and vehicle group (Group 2), and one-way ANOVA and Dunnett's test were used for statistical analysis to compare vehicle group (Group 2) and other treatment groups (Groups 3 to 13). Differences were considered statistically significant when p-value was less than 0.05 (p<0.05).

Example 2: Case Study on the Effects of the Drug Composition on the Human Body To evaluate the effects of the drug composition of the present invention on elevated BAC, a study was conducted on 25 volunteer individuals. Twenty-one men and four women between the ages of 31 and 50 were studied. Table 8 provides basic demographic details of the selected individuals.

The drug composition (hereinafter referred to as "CGW3 formulation") contains an extract of a mixture of medicinal herbs including about 5-15% by weight dried ginger, about 15-25% by weight dojin, about 25-35% by weight Poria cocos, about 15-25% by weight unripe orange peel, and about 10-20% by weight unripe white berry.

Each individual is tested for each of the following three conditions:

1) Drinking alcohol without taking CGW3 formulation (control setting)
2) Take 120 ml of the CGW3 formulation 30 minutes before and 30 minutes after drinking alcohol.

3) Take 120 ml of CGW3 formulation once a day, 30 minutes before and 30 minutes after drinking alcohol for 15 days.

Each male individual consumed 147 ml of alcohol and each female individual consumed 73.5 ml of alcohol. After consumption, the following tests and evaluations were performed by a neurologist:

(a) Practical vigilance tests include the finger-to-nose test, counting test (eyes closed counting), and Romberg balance test.

(b) Self-administered questionnaires 1 hour, 2 hours, and 24 hours after drinking. The questionnaire 1 hour after drinking concerns alcohol hangover symptoms such as dizziness, fever, sweating, headache, abdominal pain, diarrhea, itchy skin and rash, and abdominal pain. The questionnaire 2 hours after drinking concerns alcohol hangover symptoms such as incoherent speech, altered level of consciousness, confusion, unsteady walking, blurred vision, and trembling hands. The questionnaire 24 hours after drinking concerns alcohol hangover symptoms such as impaired work ability, attention or memory, nausea, vomiting, abdominal discomfort, back pain, head and neck pain, dry eye discomfort, insomnia, and lethargy.

(c) Serological tests: glucose-6-phosphate dehydrogenase (G6PD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), creatinine and aldosterone.

As shown in Figure 12 and Table 9, individuals who took 15 doses of the CGW3 formulation before drinking alcohol performed significantly better in the finger-nose test and counting test and maintained better balance compared to the control setting. Furthermore, individuals who took one dose of the CGW3 formulation before drinking alcohol performed significantly more accurate counting tests and maintained better balance compared to the control setting. As a result, taking at least one dose of the CGW3 formulation before drinking alcohol significantly improved performance in the non-standardized practical vigilance tests (finger-nose test, counting test, and balance test).

Table 10 and Figures 13-15 show that taking 1 or 15 doses of CGW3 formulation before drinking alcohol reduces all alcohol hangover symptoms. Specifically, taking 15 doses of CGW3 formulation before drinking alcohol significantly reduced dizziness, confusion, and improved next-day attention or memory compared to control settings. Taking 1 dose of CGW3 formulation before drinking alcohol significantly reduced incoherent speech, altered consciousness level, and improved next-day work performance compared to control settings.

Table 11 and Figures 16-18 show the effects of CGW3 preparation on liver function tests, renal function tests and G6PD. It is noted that compared with the control setting, taking CGW3 preparation once before drinking alcohol significantly reduces serum levels of G6PD and γ-GT, and taking CGW3 preparation 15 times before drinking alcohol significantly reduces serum levels of ALT and AST, and tends to reduce serum creatinine levels.

Example 3: In vivo study of the effect of drug pharmaceutical composition The effect of CGW3 formulation on the intestinal capsule and glomeruli in mice is evaluated.

Male C57BL/6 mice aged 8-10 weeks and weighing approximately 20 grams (purchased from the National Animal Center, Taiwan, China, and bred at the Animal Center, Chang Gung University, IACUC number CGU108-009) were used in the study. This study consisted of the following five study groups, each with 10 mice:

1. Regular control diet: Mice were fed a Lieber-DeCarli diet (221.78 g of Lieber-DeCarli standard diet powder stirred in 1 liter of distilled water) by oral gavage for 4 weeks. 12.3 ml/kg body weight/day of distilled water was administered by oral gavage 1 week before and throughout the regular control diet.

2. Liquid alcohol diet: According to the "Evaluation Method of Liver Health Care Efficacy of Healthy Food" promulgated by the Food and Drug Administration of Taiwan, China in 2016, mice were fed a Lieber-DeCarli alcohol diet (132.18 g of Lieber-DeCarli standard diet powder and 67 ml of 95% alcohol in 933 ml of distilled water) by oral gavage for 4 weeks to induce intestinal and renal damage. Distilled water at 12.3 ml/kg body weight/day was administered by oral gavage 1 week before and throughout the entire course of the liquid alcohol diet.

3. Liquid alcohol diet + 4.1 ml/kg body weight/day of CGW3 formulation: Mice were fed a Lieber-DeCarli alcohol diet by oral gavage for 4 weeks. 4.1 ml/kg body weight/day of CGW3 formulation (equivalent to 0.33 mg/kg body weight/day in humans) was administered by oral gavage once daily for 5 weeks, 1 week before and during the entire course of the liquid alcohol diet).

4. Liquid alcohol diet + 12.3 ml/kg body weight/day of CGW3 formulation: Mice were fed the Lieber-DeCarli alcohol diet by oral gavage for 4 weeks. 12.3 ml/kg body weight/day of CGW3 formulation (equivalent to 1 mg/kg body weight/day in humans) was administered once daily by oral gavage 1 week before and throughout the entire course of the liquid alcohol diet for a total of 5 weeks.

5. Liquid alcohol diet + 36.9 ml/kg bw/day of CGW3 formulation: Mice were fed the Lieber-DeCarli alcohol diet by oral gavage for 4 weeks. 36.9 ml/kg bw/day of CGW3 formulation (equivalent to 3 mg/kg bw/day in humans) was administered once daily by oral gavage 1 week before and throughout the entire course of the liquid alcohol diet for a total of 5 weeks.

After administration of the CGW3 formulation for 5 weeks, the protective effect of the CGW3 formulation on the intestinal capsule and glomeruli was evaluated.

Pathological examination After the mice were sacrificed, the jejunum and kidney tissues were fixed with 10% formalin and stained with hematoxylin and eosin protocol. Staining results: cell nuclei are blue, and cytoplasm and interstitial tissue are red.

result:
Figure 19, panel B, shows that the jejunal villi of mice fed a liquid alcohol diet are damaged compared to mice fed a normal control diet (Figure 19, panel A). The damage to the jejunal villi is reversed or attenuated by regular feeding of the CGW3 formulation (Figures 19, panels C-E).

Figure 20B shows glomerular damage in mice on a liquid alcohol diet compared to mice on a normal control diet (Figure 20A). The glomerulus is the kidney tissue in which the first urine produced by filtration is enclosed in Bowman's capsule. The main function of the glomerulus is to filter plasma to remove waste products and form urine. Glomerular damage is reversed or attenuated by regular feeding of CGW3 formulations (Figures 20C-E).

Example 4: Case study on taking pharmaceutical composition after taking red wine Two adult volunteers were recruited, taking 250mL of red wine as the control group, taking S5 pharmaceutical composition containing three components of Douglas Frühling, Poria Coccus and Unshiu Citrus Peel (the weight ratio of Douglas Frühling, Poria Coccus and Unshiu Citrus Peel is 25-35%:30-50%:25-35%) and 250mL of red wine as the experimental group 1, taking pharmaceutical composition containing three components of Douglas Frühling, Poria Coccus and Unshiu Citrus Peel (the weight ratio of Douglas Frühling, Poria Coccus and Unshiu Citrus Peel is 25-35%:30-50%:25-35%) and 250mL of red wine as the experimental group 2, and adding both Unshiu Citrus Peel and Unshiu Citrus Peel to the pharmaceutical composition to check the difference in alcohol concentration reduction, and the alcohol concentration is measured using a professional electrochemical alcohol meter (model number HOHOGA-AT576-AlcoREAL) of Hanxin Science and Technology. The mean alcohol concentrations of the two volunteers are shown in Table 12.

As can be seen from Table 12, the alcohol concentration measured after 30 minutes in experimental group 1 was lower than those in the control group and experimental group 2. Furthermore, the alcohol concentration after 90 minutes in experimental group 1 was 0, meaning that it could not be measured by an alcohol breathalyzer. As can be seen from the above results, the medicinal compositions of the present invention, the composition containing Unchimpi peel, has a stronger sobering effect than the composition containing Qing peel, and can reduce the alcohol concentration to zero in a shorter time.

Claims (5)

1. A pharmaceutical composition for treating or reducing the effects of alcohol consumption in an individual , comprising:
Toujin,
Bukryo ,
Dried tangerine peel,
Dried ginger, and
(1) a medicinal herb mixture containing Byathium rhizome ;
(2) A pharmaceutical composition comprising a pharma- ceutically acceptable carrier. 2. The pharmaceutical composition according to claim 1, wherein in said herbal mixture, the weight ratio of Doujinshi, Citrus unshiu Peel and Poria Cocos is 25-35%:25-35%:30-50%. 3. The pharmaceutical composition of claim 1 or 2, wherein the herbal mixture comprises 5-15% by weight of dried ginger, 15-25% by weight of dojin, 25-35% by weight of poria rhizome, 15-25% by weight of unripe orange peel and 10-20% by weight of bead rhizome . The pharmaceutical composition according to any one of claims 1 to 3 , wherein the pharmaceutical composition is administered before drinking alcohol. The pharmaceutical composition according to any one of claims 1 to 4 , wherein the effect of drinking alcohol is selected from the group consisting of symptoms of increased blood alcohol concentration and alcohol hangover.