Application of hippophae rhamnoides extract in preparation of product for dispelling effects of alcohol or preventing and treating visceral organ injury caused by drinking

Abstract

The invention provides application of hippophae rhamnoides extract in preparation of a product for dispelling the effects of alcohol or preventing and treating visceral organ injury caused by drinking, and belongs to the technical field of biological medicine. The invention provides application of a sea-buckthorn extract or a product containing the sea-buckthorn extract in preparation of a product for dispelling the effects of alcohol or preventing and treating visceral organ injury caused by drinking. The sea-buckthorn extract comprises sea-buckthorn fruit oil, sea-buckthorn seed oil and / or sea-buckthorn fruit pulp. The organ injury comprises alcoholic fatty liver, gastric mucosa injury or duodenum mucosa injury. The hippophae rhamnoides fruit extract (hippophae rhamnoides fruit pulp, hippophae rhamnoides fruit oil and hippophae rhamnoides fruit seed oil) and the hippophae rhamnoides fruit and Chinese wolfberry fruit composite primary pulp provided by the invention have the effects of promoting the repair of gastric mucosa and duodenal mucosa and further enhancing the immunity of gastrointestinal tracts, and can effectively prevent and / or treat gastritis, alcoholic fatty liver and duodenal mucosa injury caused by drinking; the traditional Chinese medicine composition can replace traditional medicine treatment and has the advantages of small side effect, economy, practicability, suitability for long-term administration and good compliance.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of sea buckthorn extract in the preparation of products for relieving hangovers or preventing organ damage caused by drinking. Background Technology

[0002] Long-term consumption of high-concentration alcohol has been scientifically proven to pose a serious threat to human health, particularly to the digestive, nervous, and immune systems. Among these systems, the digestive system is the first to be affected. After entering the body, alcohol directly acts on the gastric mucosa, dissolving the protective mucus on its surface, thus removing the gastric mucosa barrier and directly exposing it to the erosion of gastric acid and pepsin, leading to gastric mucosal damage and inflammation. Alcohol contributes to the occurrence and development of alcoholic gastritis through multiple pathways, including direct damage, increased gastric acid secretion, damage to submucosal blood vessels, and increased inflammatory mediators. Alcohol primarily damages the stomach by triggering acute or chronic gastritis. After heavy drinking, symptoms such as stomach pain, nausea, and vomiting may occur. Chronic gastritis is associated with long-term alcohol consumption and can lead to persistent inflammatory responses in the gastric mucosa. Alcohol affects the gastric mucosal barrier and gastric mucosal defense factors, stimulates gastric acid secretion, and leads to gastric mucosal damage and alcoholic gastritis. Alcohol can also dilate gastric mucosal blood vessels, increasing the risk of gastric mucosal bleeding.

[0003] Furthermore, after alcohol enters the body, it is primarily metabolized by the liver. Long-term excessive drinking exacerbates the burden on the liver, potentially leading to a range of liver diseases, including fatty liver, alcoholic hepatitis, alcoholic cirrhosis, and even liver cancer. Ethanol and its metabolite acetaldehyde can directly cause fatty degeneration of hepatocytes, thus triggering liver disease. These mechanisms can lead to a series of pathological changes in the liver, progressing from fatty liver to hepatitis, liver fibrosis, and cirrhosis. After alcohol enters the body, approximately 20% is absorbed in the stomach, while the remaining 80% is rapidly absorbed into the bloodstream, primarily in the duodenum and jejunum. The duodenal mucosa is directly exposed to a high concentration of alcohol. The lipid solubility of alcohol can damage the lipid barrier of the mucosal epithelial cells, leading to cell degeneration and necrosis. Simultaneously, alcohol stimulates the duodenal mucosa to release large amounts of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), triggering a local inflammatory response and further aggravating mucosal damage. Long-term or repeated damage can lead to serious complications such as duodenal ulcers and bleeding, affecting the digestion and absorption of nutrients and causing persistent harm to human health. Currently, most hangover remedies on the market for discomfort and digestive tract damage caused by alcohol consumption focus on promoting alcohol metabolism (such as those containing alcohol dehydrogenase or aldehyde dehydrogenase activators) or relieving central nervous system depression symptoms, but their effectiveness in directly protecting the duodenal mucosa and reducing inflammatory damage is limited. Furthermore, drugs used clinically to prevent and treat digestive tract mucosal damage (such as proton pump inhibitors and gastric mucosal protectants) primarily target the stomach, offering limited specific protection to the duodenum, and some drugs have adverse reactions or usage restrictions.

[0004] Current methods for preventing and treating alcohol-related gastritis, gastric mucosal damage, duodenal mucosal damage, and alcoholic fatty liver mainly include abstinence from alcohol, a reasonable diet, nutritional support, and drug therapy. The shortcomings of these preventative measures include: for individuals who have developed a dependence on alcohol over a long period, the abstinence process may be accompanied by withdrawal syndrome, requiring professional guidance and support; a reasonable diet depends on individual self-discipline and is difficult to maintain long-term; nutritional therapy requires adjustments based on individual patient conditions, making it difficult to establish uniform standards; and drug therapy must be conducted under the guidance of a doctor, and carries the risks of drug side effects and dependence. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide the application of sea buckthorn extract in the preparation of products for relieving hangovers or preventing organ damage caused by drinking.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides the application of sea buckthorn extract or products containing sea buckthorn extract in the preparation of products for relieving hangovers or preventing organ damage caused by drinking, wherein the sea buckthorn extract includes sea buckthorn fruit oil, sea buckthorn seed oil and / or sea buckthorn pulp; and the organ damage includes alcoholic fatty liver, gastric mucosal damage or duodenal mucosal damage.

[0008] Preferably, the gastric mucosal injury includes gastritis.

[0009] Preferably, the method for preparing sea buckthorn fruit oil includes the following steps: crushing sea buckthorn fruit, extracting it using supercritical carbon dioxide extraction, centrifuging it, and obtaining sea buckthorn fruit oil from the upper layer; the method for preparing sea buckthorn fruit pulp includes the following steps: crushing sea buckthorn fruit into pulp, grinding it, passing it through a 90-mesh sieve, collecting the sieved material, and obtaining sea buckthorn fruit pulp.

[0010] Preferably, the supercritical carbon dioxide extraction method has an extraction temperature of 30–60°C, a pressure of 10–30 MPa, and a CO2 flow rate of 5–20 L / h.

[0011] Preferably, the centrifugation speed is 3000-6000 rpm and the time is 15-40 min.

[0012] Preferably, the preparation method of the sea buckthorn seed oil includes the following steps: crushing the sea buckthorn seeds, extracting them using supercritical carbon dioxide extraction, separating the solid and liquid components, and obtaining sea buckthorn seed oil.

[0013] Preferably, the supercritical carbon dioxide extraction method has an extraction temperature of 35–60°C, a pressure of 15–35 MPa, and a CO2 flow rate of 8–25 L / h; the pulverized particle size is 0.5–2 mm.

[0014] Preferably, the solid-liquid separation method includes centrifugation, wherein the centrifugation speed is 4000-8000 rpm and the time is 15-40 min.

[0015] The present invention also provides a compound fruit pulp of sea buckthorn and wolfberry, which is composed of sea buckthorn fruit pulp and wolfberry fruit pulp, wherein the volume ratio of sea buckthorn fruit pulp to wolfberry fruit pulp is 1:(2-4); the preparation method of the sea buckthorn fruit pulp includes the following steps: crushing sea buckthorn fruit into pulp, grinding, passing through a 90-mesh sieve, collecting the sieved material, and obtaining sea buckthorn fruit pulp; the preparation method of the wolfberry fruit pulp includes the following steps: crushing wolfberry into pulp, grinding, passing through a 90-mesh sieve, homogenizing, and sterilizing, and obtaining wolfberry fruit pulp.

[0016] The present invention also provides the application of the above-mentioned sea buckthorn and wolfberry compound fruit pulp in the preparation of products for relieving hangovers or preventing organ damage caused by drinking, wherein the organ damage includes alcoholic fatty liver, gastric mucosal damage or duodenal mucosal damage.

[0017] The beneficial effects of this invention are:

[0018] The sea buckthorn extracts (sea buckthorn pulp, sea buckthorn fruit oil, and sea buckthorn seed oil) provided by this invention all have the effect of promoting the repair of gastric or duodenal mucosa damage, thereby enhancing gastrointestinal immunity. They can effectively prevent and / or treat gastritis and alcoholic fatty liver caused by alcohol consumption, and can replace traditional drug treatments. They have the advantages of few side effects, affordability, suitability for long-term use, and good compliance. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the supercritical carbon dioxide extraction device of the present invention, wherein ① is the extraction vessel, ② is the separation column, ③ is the heat exchanger, ④ is the condenser, ⑤ is the cryogenic cooler, ⑥ is the pump, ⑦ is the heat exchanger, and ⑧ is the storage tank.

[0020] Figure 2 The results of the intoxication time in the first low-dose alcohol experiment for mice in different groups;

[0021] Figure 3 The results of the intoxication time on each day of the first low-dose alcohol experiment for mice in different groups are shown. # indicates p < 0.05 compared with the control group, and * indicates p < 0.05 compared with the model group.

[0022] Figure 4 The results of the intoxication time on each day in the second high-dose alcohol experiment for mice in different groups are shown. # indicates p < 0.05 compared with the control group, and * indicates p < 0.05 compared with the model group.

[0023] Figure 5 The results of the intoxication time in mice of different groups during the second high-dose alcohol experiment;

[0024] Figure 6 HE staining and immunohistochemical results of gastric tissue;

[0025] Figure 7 HE staining and immunohistochemical results of the duodenal mucosa;

[0026] Figure 8 The results of HE staining of liver tissue. Detailed Implementation

[0027] This invention provides the application of sea buckthorn extract or products containing sea buckthorn extract in the preparation of products for relieving hangovers or preventing organ damage caused by drinking, wherein the sea buckthorn extract includes sea buckthorn fruit oil, sea buckthorn seed oil and / or sea buckthorn pulp; and the organ damage includes alcoholic fatty liver, gastric mucosal damage or duodenal mucosal damage.

[0028] This invention is the first to propose that sea buckthorn fruit oil, sea buckthorn seed oil, or sea buckthorn pulp have significant effects on gastritis caused by alcohol, and also alleviate symptoms such as weight loss and loss of appetite caused by alcohol, as well as symptoms of drunkenness. The sea buckthorn extract of this invention can form a protective film on the gastric mucosa, reducing the stimulation and damage to the gastric mucosa by gastric acid, pepsin, etc.; it can promote the repair and regeneration of damaged gastric mucosa, accelerating the recovery process of gastritis; it can enhance the body's immune function, improve the stomach's resistance to pathogens, and reduce the risk of gastritis recurrence. In this invention, the gastric mucosal damage preferably includes gastritis. This invention does not specifically limit the specific types of products containing sea buckthorn extract; the products include compound products made by combining sea buckthorn extract with other foods, drugs, etc.

[0029] This invention is the first to propose that sea buckthorn seed oil, sea buckthorn fruit oil, or sea buckthorn pulp have significant therapeutic and preventive effects on alcoholic fatty liver. The mechanisms of action include antioxidant effects, promotion of lipid metabolism, protection of liver cells, promotion of liver cell regeneration, anti-inflammatory effects, and provision of energy and acceleration of alcohol decomposition.

[0030] This invention is the first to propose that sea buckthorn seed oil, sea buckthorn fruit oil, or sea buckthorn fruit pulp have significant therapeutic and preventative effects on alcohol-induced duodenal mucosal damage.

[0031] Experiments have confirmed that the sea buckthorn extract of this invention has a significant protective effect on the gastric mucosa, and the duration of intoxication varies significantly depending on the timing of administration. Full-spectrum metabolomics analysis revealed that sea buckthorn seed oil and sea buckthorn pulp are rich in metabolites, leading to sea buckthorn's ability to reduce alcohol absorption. This differs from currently reported mechanisms of action in the field, which involve increasing alcohol metabolism to alleviate hangovers. The reasons why the sea buckthorn extract of this invention has preventive and therapeutic effects against alcoholic fatty liver, gastric mucosal damage, or duodenal mucosal damage are as follows:

[0032] (1) Strengthening the gastric mucosal barrier - physically blocking alcohol penetration:

[0033] Sea buckthorn fruit oil forms a hydrophobic protective film: Sea buckthorn seed oil is rich in palmitoleic acid (ω-7) and linoleic acid (ω-6), which can form a dense oil film barrier on the surface of the gastric mucosa, significantly reducing the direct contact between alcohol and gastric epithelial cells and reducing the passive diffusion and absorption of alcohol.

[0034] The gelling effect of pectin and polysaccharides: The water-soluble dietary fiber (pectin and sea buckthorn polysaccharides) in sea buckthorn pulp swells in the gastric acid environment, forming a high-viscosity gel network that encapsulates alcohol molecules and slows down their transfer rate to the small intestine (the main site of alcohol absorption).

[0035] (2) Gastrointestinal motility regulation - delaying gastric emptying:

[0036] Organic acids inhibit gastric motility: Malic acid, oxalic acid and other organic acids in sea buckthorn can moderately reduce the frequency of gastric smooth muscle contraction, prolong the time alcohol stays in the stomach, and allow more alcohol to be pre-metabolized by alcohol dehydrogenase (ADH) in the stomach (gastric ADH activity accounts for about 10% of the whole body), thus reducing the total amount of alcohol entering the bloodstream.

[0037] Sea buckthorn peptides regulate gastrointestinal hormones: Bioactive peptides in sea buckthorn protease hydrolysates can inhibit the secretion of gastrointestinal hormones, suppress gastric emptying, and indirectly reduce the efficient absorption of alcohol in the small intestine.

[0038] (3) Strengthening of tight junctions in the gut - reducing intestinal epithelial permeability

[0039] Sea buckthorn metabolites enhance tight junction proteins: Sea buckthorn metabolites repair alcohol-induced widening of intestinal epithelial cell gaps and reduce transcellular bypass transport of alcohol by activating the expression of proteins such as ZO-1 and Claudin.

[0040] Sea buckthorn metabolites stabilize cell membrane structure: Sea buckthorn metabolites embed in the phospholipid bilayer of intestinal epithelial cell membrane, enhancing membrane structural stability and inhibiting the lipid-soluble penetration of alcohol.

[0041] In this invention, the preferred method for preparing sea buckthorn fruit oil includes the following steps: crushing sea buckthorn fruit, extracting it using supercritical carbon dioxide extraction, centrifuging it, and obtaining sea buckthorn fruit oil from the upper layer; the preferred method for preparing sea buckthorn fruit pulp includes the following steps: crushing sea buckthorn fruit into a pulp, grinding it, passing it through a 90-mesh sieve, collecting the sieved material, and obtaining sea buckthorn fruit pulp.

[0042] This invention does not specifically limit the method for crushing sea buckthorn berries. In some embodiments of this invention, the crushing method is mechanical pressing, grinding, or crushing. In this invention, when the crushed sea buckthorn berries are extracted using supercritical carbon dioxide extraction, the extraction temperature is preferably 30–60°C, more preferably 40–55°C, and even more preferably 45–52°C; the extraction pressure is preferably 10–30 MPa, more preferably 15–25 MPa, and even more preferably 18–22 MPa; the CO2 flow rate is preferably 5–20 L / h, more preferably 8–18 L / h, and even more preferably 9–15 L / h. In this invention, after extraction, the extract is collected and centrifuged. The centrifugation speed is preferably 3000–6000 rpm, more preferably 3800–5800 rpm, and even more preferably 4500–5500 rpm; the centrifugation time is preferably 15–40 min, more preferably 20–35 min, and even more preferably 25–32 min. In the preparation method of sea buckthorn pulp of the present invention, fresh sea buckthorn berries are preferably washed, dehydrated, and pulped into a pulp using a pulping machine; then ground in a colloid mill for 4-6 minutes to achieve a pulp fineness of 90 mesh. In this invention, small-fruited sea buckthorn from Ningxia, Qinghai, and Gansu is preferred, and frost-damaged berries are selected (for more complete sugar conversion). Metal containers are avoided (as they will destroy vitamin C). The entire process is carried out in the dark (to prevent oxidation of nutrients), and the temperature is controlled to not exceed 40°C (to protect active enzymes).

[0043] In this invention, the preferred method for preparing sea buckthorn seed oil includes the following steps: crushing sea buckthorn seeds, extracting them using supercritical carbon dioxide extraction, separating the solid and liquid phases, and obtaining sea buckthorn seed oil.

[0044] This invention does not specifically limit the method of pulverizing sea buckthorn seeds; any conventional pulverizing method in the art can be used. In this invention, it is preferred to pulverize the sea buckthorn seeds to a particle size of 0.5–2 mm. In some embodiments of this invention, the particle size is 0.5 mm, 0.8 mm, 1.0 mm, 1.3 mm, 1.6 mm, 1.8 mm, or 2 mm. In this invention, when using supercritical carbon dioxide extraction to extract the pulverized sea buckthorn seeds, the extraction temperature is preferably 35–60°C, more preferably 40–58°C, and even more preferably 48–56°C; the extraction pressure is preferably 15–35 MPa, more preferably 18–32 MPa, and even more preferably 20–30 MPa; the CO2 flow rate is preferably 8–25 L / h, more preferably 10–20 L / h, and even more preferably 13–18 L / h. In this invention, the solid-liquid separation method preferably includes centrifugation, the centrifugation speed is preferably 4000-8000 rpm, more preferably 5000-7000 rpm, and even more preferably 5500-6500 rpm; the centrifugation time is preferably 15-40 min, more preferably 20-35 min, and even more preferably 25-32 min.

[0045] The present invention also provides a compound fruit pulp of sea buckthorn and wolfberry, which is composed of sea buckthorn fruit pulp and wolfberry fruit pulp, wherein the volume ratio of sea buckthorn fruit pulp to wolfberry fruit pulp is 1:(2-4); the preparation method of the sea buckthorn fruit pulp includes the following steps: crushing sea buckthorn fruit into pulp, grinding, passing through a 90-mesh sieve, collecting the sieved material, and obtaining sea buckthorn fruit pulp; the preparation method of the wolfberry fruit pulp includes the following steps: crushing wolfberry into pulp, grinding, passing through a 90-mesh sieve, homogenizing, and sterilizing, and obtaining wolfberry fruit pulp.

[0046] In some embodiments of the present invention, the volume ratio of sea buckthorn pulp to goji berry pulp is 1:2, 1:3, or 1:4. In the sea buckthorn and goji berry compound pulp of the present invention, the preparation method of the sea buckthorn pulp is the same as above and will not be repeated here. In the present invention, the preferred method for preparing the goji berry pulp includes the following steps: crushing and pulping goji berries, grinding them, passing them through a 90-mesh sieve, homogenizing, and sterilizing to obtain goji berry pulp. In this invention, the method for preparing wolfberry pulp more preferably includes the following steps: Fresh wolfberry fruits are inspected within 8 days of harvesting, damaged fruits are removed, and the lead content is ensured to be ≤0.05mg / kg and free from Salmonella contamination; subsequently, a four-stage deep cleaning process is performed: first, soaking in chlorine dioxide disinfectant to remove pesticide residues; then, two-stage bubbling cleaning (a blower agitates the fruit with water flow); finally, rinsing and draining with ultrafiltration reverse osmosis sterile water; the cleaned fruits are vibrated, drained, and blown dry before being sent to a crushing and pulping system: a hammer crusher pre-crushes the fruit at 1470-1500rpm, and then processes it step-by-step by a double-stage pulper (first stage at 45-50Hz, second stage at 48-52Hz) to separate the fruit. The seeds and pulp yield is increased to 85%. The pulp is ground to ≥90 mesh using a colloid mill at 2950–3000 rpm to release polysaccharides and carotenoids. Industrial-grade production requires high-pressure homogenization (30–40 MPa) to prevent stratification, followed by vacuum degassing under nitrogen protection (0.03–0.06 MPa) to prevent oxidation. Sterilization is performed using UHT instantaneous technology (110℃±3℃ for 30–40 seconds) to retain over 90% of vitamin C, or pasteurization (83–87℃ for 25–30 minutes). Finally, the pulp is filled into light-proof containers in a sterile chamber at ≥95℃, and then sealed at 35℃ to form 100% additive-free puree. Home production can be simplified to rinsing with water, juicing, coarse filtration, and boiling for sterilization, but this results in a 40% nutrient loss and a shelf life of only 7 days under refrigeration. The industrial process provided by this invention maximizes the retention of active ingredients (≥4.76g of wolfberry polysaccharides per 100g) through low-temperature crushing and instantaneous sterilization. The wolfberry pulp preparation process of this invention requires complete darkness protection. In this invention, the wolfberries are preferably purchased from the Zhongning production area of ​​Ningxia.

[0047] The present invention also provides the application of the above-mentioned sea buckthorn and wolfberry compound fruit pulp in the preparation of products for relieving hangovers or preventing organ damage caused by drinking, wherein the organ damage includes alcoholic fatty liver, gastric mucosal damage or duodenal mucosal damage.

[0048] In this invention, the products preferably include food, food and medicine homology, health products and drugs.

[0049] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0050] Unless otherwise specified, the following embodiments are all conventional methods.

[0051] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0052] Example 1

[0053] Preparation of sea buckthorn fruit oil:

[0054] Sea buckthorn fruit oil was prepared using supercritical carbon dioxide extraction, and a schematic diagram of the supercritical carbon dioxide extraction apparatus used is shown below. Figure 1 As shown, the specific preparation method is as follows:

[0055] After crushing the sea buckthorn berries, they were placed in an extraction vessel, and the required extraction temperature was set to 50℃. CO2 from the storage tank was pressurized by a pump and preheated to the set temperature of 50℃ in a heat exchanger. The inlet valve was opened to allow the CO2 fluid to enter the extraction vessel and contact the crushed sea buckthorn berries. The CO2 flow rate was controlled at 10 L / h. Under the set extraction temperature of 50℃ and pressure of 20 MPa, the sea buckthorn oil contained in the berries was fully dissolved in the supercritical CO2. After a residence time of 25 minutes, the product was discharged. The sea buckthorn oil and CO2 were separated in a separation column. The separated product was collected after being discharged through a vent valve. The CO2 gas was recycled back to the storage tank after passing through a heat exchanger, condenser, and cryostat. Recycling was stopped when almost no product could be collected at the vent valve. The product collected from the vent valve was centrifuged at 5000 rpm for 30 minutes; the upper layer was sea buckthorn oil.

[0056] Example 2

[0057] Preparation of sea buckthorn fruit oil: The difference from Example 1 is that the supercritical carbon dioxide extraction temperature is 30℃, the pressure is 10MPa, the CO2 flow rate is 5L / h, and the centrifugation conditions are 3000rpm for 40min. All other conditions are the same as in Example 1.

[0058] Example 3

[0059] Preparation of sea buckthorn fruit oil: The difference from Example 1 is that the supercritical carbon dioxide extraction temperature is 60℃, the pressure is 30MPa, the CO2 flow rate is 20L / h, and the centrifugation conditions are 6000rpm for 15min. All other conditions are the same as in Example 1.

[0060] Example 4

[0061] Preparation of sea buckthorn seed oil:

[0062] Sea buckthorn seed oil is prepared using supercritical carbon dioxide extraction, and a schematic diagram of the supercritical carbon dioxide extraction apparatus used is shown below. Figure 1 As shown, the specific preparation method is as follows:

[0063] Sea buckthorn seeds were crushed to a particle size of 1 mm and then placed into an extraction vessel. The required extraction temperature was set to 55℃. CO2 from the storage tank was pressurized by a pump and preheated to the set temperature of 55℃ in a heat exchanger. The inlet valve was opened to allow the CO2 fluid to enter the extraction vessel and contact the crushed sea buckthorn seeds. The CO2 flow rate was controlled at 15 L / h. At the set extraction temperature of 55℃ and pressure of 25 MPa, the sea buckthorn seed oil contained in the sea buckthorn seeds was fully dissolved in the supercritical CO2. After a residence time of 25 min, the product was discharged. The sea buckthorn seed oil and CO2 were separated in a separation column. The separated product was discharged through the vent valve and collected. The CO2 gas was recycled back into the storage tank after passing through a heat exchanger, condenser, and cryostat. The recycling was stopped when almost no product could be collected at the vent valve. The product collected from the vent valve was centrifuged at 6000 rpm for 30 min. The upper layer was sea buckthorn seed oil.

[0064] Example 5

[0065] Preparation of sea buckthorn seed oil: The difference from Example 4 is that the sea buckthorn seeds are crushed to a particle size of 0.5 mm, the supercritical carbon dioxide extraction temperature is 35 °C, the pressure is 15 MPa, the CO2 flow rate is 8 L / h, and the centrifugation conditions are 4000 rpm for 40 min. All other conditions are the same as in Example 4.

[0066] Example 6

[0067] Preparation of sea buckthorn seed oil: The difference from Example 4 is that the sea buckthorn seeds are crushed to a particle size of 2 mm, the supercritical carbon dioxide extraction temperature is 60°C, the pressure is 35 MPa, the CO2 flow rate is 25 L / h, and the centrifugation conditions are 8000 rpm for 15 min. All other conditions are the same as in Example 4.

[0068] Example 7

[0069] Preparation of sea buckthorn pulp: Wash fresh sea buckthorn berries, dehydrate them, and grind them into pulp using a pulping machine; then grind them in a colloid mill for 6 minutes to make the pulp fineness reach 90 mesh, pass it through a 90 mesh sieve, collect the sieved material, and obtain sea buckthorn pulp.

[0070] Example 8

[0071] A compound fruit pulp of sea buckthorn and goji berries, comprising sea buckthorn pulp and goji berry pulp, wherein the volume ratio of sea buckthorn pulp to goji berry pulp is 1:2;

[0072] The preparation method of the sea buckthorn pulp is the same as in Example 7; the preparation method of the goji berry pulp is as follows: fresh goji berries are inspected within 8 days after harvesting, broken berries are removed, and the lead content is ensured to be ≤0.05mg / kg and free from Salmonella contamination; then, a four-stage deep cleaning is performed: first, soaking in chlorine dioxide disinfectant to remove pesticide residues, then two-stage bubbling cleaning, with a blower blowing water to tumble the berries, and finally rinsing and draining with ultrafiltration reverse osmosis sterile water; the cleaned berries are vibrated, drained, and blown dry, and then sent to the crushing and pulping system: a hammer crusher pre-crushes at 1470rpm, and then passes through a double-stage pulping machine for step-by-step processing. The pulp undergoes two stages: a first stage at 45 Hz and a second stage at 48 Hz to separate seeds and pulp, increasing the pulp yield to 85%. The pulp is then ground to ≥90 mesh using a colloid mill at 2950 rpm to release polysaccharides and carotenoids. High-pressure homogenization at 30 MPa prevents stratification, and vacuum degassing at 0.03 MPa under nitrogen protection prevents oxidation. Sterilization is performed using UHT instantaneous technology, maintaining 110℃ for 30 seconds to retain over 90% of vitamin C. Finally, the pulp is filled into light-proof containers in a sterile chamber at ≥95℃, and then sealed at 35℃ to form 100% additive-free pure pulp.

[0073] Example 9

[0074] A compound fruit pulp of sea buckthorn and goji berries, comprising sea buckthorn pulp and goji berry pulp, wherein the volume ratio of sea buckthorn pulp to goji berry pulp is 1:4;

[0075] The preparation method of the sea buckthorn pulp is the same as in Example 7; the preparation method of the wolfberry pulp is the same as in Example 8.

[0076] Example 10

[0077] A compound fruit pulp of sea buckthorn and goji berries, comprising sea buckthorn pulp and goji berry pulp, wherein the volume ratio of sea buckthorn pulp to goji berry pulp is 1:3;

[0078] The preparation method of the sea buckthorn pulp is the same as in Example 7; the preparation method of the wolfberry pulp is the same as in Example 8.

[0079] Example 11

[0080] Healthy male ICR mice, SPF grade, aged 4 to 5 weeks and weighing 20g–22g, were selected for the experiment. All mice were purchased from legitimate sources. The mice were housed in the SPF-grade animal facility of Ningxia Medical University, ensuring a specific pathogen-free environment. Environmental parameters: Temperature: maintained at 20–24℃, providing a suitable constant temperature environment for the mice; Humidity: relative humidity controlled at 55%, ensuring the comfort of the mice's living environment; Light: a 12-hour light / 12-hour dark cycle was implemented to simulate the natural diurnal rhythm and maintain the mice's normal physiological rhythms. Ethical compliance: All procedures involving animals strictly adhered to the standards and regulations of the Animal Ethics Committee of Ningxia Medical University, ensuring the ethical nature and animal welfare of the experiment. The experiment followed the 3R principle.

[0081] First low-dose alcohol experiment:

[0082] Before the formal experiment, mice were first subjected to a week of environmental acclimatization feeding to ensure they could adapt to the experimental environment and reduce potential stress responses. Mice were randomly divided into a control group, a model group, a prevention group using seabuckthorn seed oil (as in Example 4), a prevention group using seabuckthorn fruit oil (as in Example 1), a prevention group using seabuckthorn fruit pulp (as in Example 7), and a prevention group using seabuckthorn and wolfberry compound fruit pulp (as in Example 8). Except for the control group, all other groups were administered 10 mL / kg of 52° baijiu (a type of Chinese liquor) by gavage for four consecutive days. Except for the control and model groups, each group was also administered 100 μL / mouse of the corresponding product after gavage with baijiu. The time to intoxication for each group was recorded.

[0083] The results are as follows Figure 2 and Figure 3 As shown, mice given only baijiu (a type of Chinese liquor) via gavage (model group) experienced an intoxication time of approximately 45 minutes. However, mice given a combination of fruit oil, seed oil, fruit pulp, and sea buckthorn / goji berry puree all showed effective detoxification, shortening the intoxication time. This detoxification effect persisted from day one to day four, indicating that the mice developed alcohol tolerance. From day one, when baijiu was administered, to day four, the mice developed alcohol tolerance, resulting in a shorter intoxication time. However, various interventions further reduced the intoxication time by building upon the mice's alcohol tolerance.

[0084] Second high-dose alcohol experiment:

[0085] Four days after the first low-dose alcohol experiment, mice developed tolerance to the low-dose alcohol. Based on this, the dosage of baijiu (a type of Chinese liquor) was increased, with mice receiving 15 mL / kg of 52° baijiu via gavage for four consecutive days. Simultaneously, the corresponding product for each group was administered via gavage (100 μL / mouse). Results are as follows... Figure 4 and Figure 5As shown, mice administered only baijiu (a type of Chinese liquor) via gavage (model group) experienced an intoxication time of approximately 120 minutes. However, mice given a combination of fruit oil, seed oil, fruit pulp, and sea buckthorn and goji berry puree all showed effective detoxification, shortening the intoxication time. The detoxification effect persisted from day 5 to day 8, although the mice still exhibited alcohol tolerance. From day 5, when high-dose baijiu was administered, the mice again developed tolerance to high-dose alcohol by day 8, resulting in a shorter intoxication time. However, various interventions further reduced intoxication time by addressing the underlying alcohol tolerance.

[0086] The reason for choosing a first low-dose alcohol experiment and a second high-dose alcohol experiment in this invention is that, considering the body's tolerance, prolonged drinking can lead to a certain degree of alcohol tolerance. This invention uses a low-dose alcohol experiment in the first phase. After the mice develop alcohol tolerance, the second high-dose alcohol experiment is then conducted. This avoids the development of alcohol tolerance while demonstrating that sea buckthorn extract has a significant sobering effect on both early low-dose drinking and later, heavy drinking after alcohol tolerance has been established.

[0087] Example 12

[0088] Establishment, grouping, and administration of alcoholic gastritis and alcoholic fatty liver in mice:

[0089] Healthy male ICR mice, SPF grade, aged 4 to 5 weeks and weighing 20g–22g, were selected for the experiment. All mice were purchased from legitimate sources. The mice were housed in the SPF-grade animal facility of Ningxia Medical University, ensuring a specific pathogen-free environment. Environmental parameters: Temperature: maintained at 20–24℃, providing a suitable constant temperature environment for the mice; Humidity: relative humidity controlled at 55%, ensuring the comfort of the mice's living environment; Light: a 12-hour light / 12-hour dark cycle was implemented to simulate the natural diurnal rhythm and maintain the mice's normal physiological rhythms. Ethical compliance: All procedures involving animals strictly adhered to the standards and regulations of the Animal Ethics Committee of Ningxia Medical University, ensuring the ethical nature and animal welfare of the experiment. The experiment followed the 3R principle.

[0090] Before the formal experiment, the mice underwent a week-long environmental acclimatization feeding period to ensure they could adapt to the experimental environment and reduce potential stress responses. During this phase, preliminary measurements of blood glucose and body weight were taken to obtain baseline data. Subsequently, based on these measurements, the mice were randomly assigned to five different experimental groups, with three mice in each group, as follows: control group, model group, sea buckthorn seed oil prevention group (seed oil group) obtained in Example 4, sea buckthorn fruit oil prevention group (fruit oil group) obtained in Example 1, sea buckthorn fruit pulp prevention group (fruit pulp group) obtained in Example 7, and sea buckthorn and wolfberry compound fruit pulp group (sea buckthorn and wolfberry compound puree) obtained in Example 8.

[0091] During the experiment, mice in the control group were given 0.2 mL of physiological saline by gavage, while mice in the model group were given continuous high-proof liquor (52°) by gavage. The three prevention groups were given fruit oil, seed oil, and fruit pulp by gavage for 30 minutes, followed by high-proof liquor (52°) by gavage, to evaluate their preventive effects. The gavage treatment lasted for 8 days (both the model group and the prevention group were given 10 times their body weight of liquor by gavage for the first four days and 15 times their body weight of liquor by gavage for the last four days).

[0092] On the eighth day of the experiment, one mouse was randomly selected from each group, and its gastric tissue, liver tissue, and duodenal mucosa were stained with hematoxylin and eosin (HE). Immunohistochemistry (interleukin-1) was also performed on the gastric tissue. HE staining of the gastric tissue revealed histological changes such as inflammatory response, cell infiltration, mucosal damage, atrophy, and intestinal metaplasia, typical manifestations of alcoholic gastritis. In liver tissue, the presence of lipid droplet deposition and fat vacuolar degeneration in hepatocytes was used as the criteria for successful model establishment.

[0093] Observation of HE staining morphology and immunohistochemical results of gastric sections are as follows: Figure 6 As shown in the figure, HE staining revealed histological changes in the stomach of the model group compared to the control group, including inflammatory response, cell infiltration, mucosal damage, atrophy, and intestinal metaplasia. The four prevention groups showed reduced gastric mucosal damage compared to the model group.

[0094] Results of HE staining of duodenal mucosa sections as follows Figure 7 As shown, the results indicate that sea buckthorn fruit oil, sea buckthorn seed oil, sea buckthorn fruit pulp, and sea buckthorn and wolfberry compound pulp can protect the duodenal mucosa.

[0095] HE staining results of liver tissue as follows Figure 8 As shown, the livers of the model group had significantly more fat vacuoles than the control group, while the fat vacuoles in the fruit oil group, seed oil group, fruit pulp group, and sea buckthorn and wolfberry compound pulp group were significantly reduced compared with the model group.

[0096] Example 13

[0097] Healthy male ICR mice, SPF grade, aged 4 to 5 weeks and weighing 20g–22g, were selected for the experiment. All mice were purchased from legitimate sources. The mice were housed in the SPF-grade animal facility of Ningxia Medical University, ensuring a specific pathogen-free environment. Environmental parameters: Temperature: maintained at 20–24℃, providing a suitable constant temperature environment for the mice; Humidity: relative humidity controlled at 55%, ensuring the comfort of the mice's living environment; Light: a 12-hour light / 12-hour dark cycle was implemented to simulate the natural diurnal rhythm and maintain the mice's normal physiological rhythms. Ethical compliance: All procedures involving animals strictly adhered to the standards and regulations of the Animal Ethics Committee of Ningxia Medical University, ensuring the ethical nature and animal welfare of the experiment. The experiment followed the 3R principle.

[0098] Mice were randomly divided into a blank control group, an alcohol model group, a seabuckthorn seed oil prevention group (seed oil group) obtained in Example 4, a seabuckthorn fruit oil prevention group (fruit oil group) obtained in Example 1, a seabuckthorn fruit pulp prevention group (fruit pulp group) obtained in Example 7, and a seabuckthorn and wolfberry compound fruit pulp group (seabuckthorn and wolfberry compound puree) obtained in Example 8. An acute alcohol intoxication model was constructed according to the treatments shown in Table 1.

[0099] Table 1 Treatment methods for different groups

[0100]

[0101] The detection indicators are: intoxication behavior: time to disappearance of righting reflex (minutes) — quantifying the speed of sobering up; gastric mucosal damage: gastric tissue HE staining ulcer index (0-5 points); metabolic enzyme activity: gastric mucosal ADH enzyme activity (U / mg protein); oxidative stress: gastric tissue SOD activity and MDA content.

[0102] The results are shown in Table 2. The intoxication time of the sea buckthorn and wolfberry compound pulp group was shortened by 66.2% (righting reflex time 35.1 seconds vs 78.3 seconds), which was significantly better than that of the single component (p<0.05). The sea buckthorn and wolfberry compound pulp activated the activity of gastric mucosal ADH enzyme (191% higher than the model group), thus achieving rapid acetaldehyde metabolism and avoiding the limitation of traditional products that rely solely on liver metabolism.

[0103] Table 2. Intervention effects of various components of sea buckthorn on an acute alcohol intoxication model.

[0104] Group Righting reflection time (seconds) Gastric ulcer index Gastric mucosal ADH activity SOD activity MDA content Alcohol model group 78.3±5.1 3.8±0.4 12.5±1.2 35.2±3.0 8.1±0.7 Sea buckthorn seed oil group 42.6±4.3* 1.2±0.3* 28.7±2.1* 48.5±4.1 4.3±0.5* Sea buckthorn fruit oil group 51.7±4.8* 1.8±0.3* 22.4±1.8* 42.3±3.7 5.1±0.6* Sea buckthorn pulp group 47.2±4.5* 1.5±0.2* 31.6±2.5* 52.1±4.3 3.9±0.4* Sea buckthorn and wolfberry compound pulp group 35.1±3.8*# 0.8±0.2*# 36.4±3.0*# 60.3±5.2 2.7±0.3*#

[0105] Note: *vs alcohol group p<0.05; #vs other sea buckthorn groups p<0.05

[0106] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The application of sea buckthorn extract or products containing sea buckthorn extract in the preparation of products for relieving hangovers or preventing organ damage caused by alcohol consumption, characterized in that, The sea buckthorn extract includes sea buckthorn fruit oil, sea buckthorn seed oil, and / or sea buckthorn pulp; the organ damage includes alcoholic fatty liver, gastric mucosal damage, or duodenal mucosal damage.

2. The application according to claim 1, characterized in that, The gastric mucosal damage includes gastritis.

3. The application according to claim 1, characterized in that, The method for preparing sea buckthorn fruit oil includes the following steps: crushing sea buckthorn fruit, extracting it using supercritical carbon dioxide extraction, centrifuging it, and obtaining sea buckthorn fruit oil from the upper layer; the method for preparing sea buckthorn fruit pulp includes the following steps: crushing sea buckthorn fruit into pulp, grinding it, passing it through a 90-mesh sieve, collecting the sieved material, and obtaining sea buckthorn fruit pulp.

4. The application according to claim 3, characterized in that, The supercritical carbon dioxide extraction method has an extraction temperature of 30–60℃, a pressure of 10–30 MPa, and a CO2 flow rate of 5–20 L / h.

5. The application according to claim 3, characterized in that, The centrifugation speed is 3000-6000 rpm, and the time is 15-40 min.

6. The application according to claim 1, characterized in that, The preparation method of the sea buckthorn seed oil includes the following steps: crushing the sea buckthorn seeds, extracting them using supercritical carbon dioxide extraction, separating the solid and liquid components, and obtaining the sea buckthorn seed oil.

7. The application according to claim 6, characterized in that, The supercritical carbon dioxide extraction method has an extraction temperature of 35–60°C, a pressure of 15–35 MPa, and a CO2 flow rate of 8–25 L / h; the particle size of the pulverized material is 0.5–2 mm.

8. The application according to claim 6, characterized in that, The solid-liquid separation method includes centrifugation, wherein the centrifugation speed is 4000-8000 rpm and the time is 15-40 min.

9. A compound fruit pulp of sea buckthorn and goji berries, characterized in that, The product is composed of sea buckthorn pulp and wolfberry pulp, wherein the volume ratio of sea buckthorn pulp to wolfberry pulp is 1:(2-4); the preparation method of the sea buckthorn pulp includes the following steps: crushing sea buckthorn fruit into a pulp, grinding, passing through a 90-mesh sieve, collecting the sieved material, and obtaining sea buckthorn pulp; the preparation method of the wolfberry pulp includes the following steps: crushing wolfberries into a pulp, grinding, passing through a 90-mesh sieve, homogenizing, and sterilizing, and obtaining wolfberry pulp.

10. The application of the sea buckthorn and wolfberry compound fruit pulp according to claim 9 in the preparation of products for relieving hangovers or preventing organ damage caused by drinking, characterized in that, The organ damage includes alcoholic fatty liver, gastric mucosal damage, or duodenal mucosal damage.

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