Ovotransferrin-nervonic acid-Gynostemma pentaphyllum compound for improving alcoholic hepatitis
By using a compound of ovotransferrin, nervonic acid, and Gynostemma pentaphyllum extract to synergistically regulate iron homeostasis and signaling pathways, the limitations of existing technologies in the treatment of alcoholic hepatitis have been overcome, resulting in the improvement of liver lesions and the enhancement of liver function indicators.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NANCHANG UNIV
- Filing Date
- 2026-07-06
- Publication Date
- 2026-07-31
AI Technical Summary
Existing technologies have limitations in treating alcoholic hepatitis. Traditional methods such as abstinence from alcohol, nutritional support, and drug therapy have limited effectiveness, and the bioavailability and safety issues of natural ingredients have not been effectively resolved.
A compound of ovotransferrin, nervonic acid, and Gynostemma pentaphyllum extract, in a specific ratio of ovotransferrin:nervonic acid:Gynostemma pentaphyllum extract = 10-30: 5-15: 20-40, was used to synergistically improve alcoholic hepatitis by regulating iron homeostasis, membrane stability, and signaling pathways.
It significantly reduces hepatomegaly, vacuolar changes in the liver, and increased lipid droplets, and improves liver function indicators ALT and AST, with good bioavailability and safety.
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Figure CN122479094A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical technology, and in particular relates to an ovotransferrin-nervonic acid-Gynostemma pentaphyllum compound for improving alcoholic hepatitis. Background Technology
[0002] Alcoholic hepatitis (AH) is a severe inflammatory liver disease caused by long-term excessive alcohol consumption. Its pathological features include hepatocellular steatosis, ballooning degeneration, inflammatory cell infiltration, and Mallory-Denk body formation. Currently, clinical treatments for alcoholic hepatitis are limited, primarily focusing on alcohol abstinence, nutritional support, and drug therapy (such as glucocorticoids). However, these methods have limitations; for example, glucocorticoids are only suitable for severe alcoholic hepatitis with a high risk of infection and are not suitable for long-term use.
[0003] In the treatment of liver injury using natural products, various plant extracts and natural components have been studied. For example, silymarin, a flavonoid-lignan complex extracted from milk thistle, possesses definite hepatoprotective properties, but its clinical application is limited by low bioavailability, mainly due to poor water solubility and high crystallinity. Traditional Chinese medicine formulas are also widely used in the treatment of liver injury. For example, compound effervescent liver-protecting granules (CEHG) alleviate liver damage by regulating the HIF-1, p53, and FoxO signaling pathways. However, the complex composition of traditional Chinese medicine formulas presents challenges in quality control and standardized production. Furthermore, the hepatoprotective effects of single components are limited. For example, taurine has been shown to alleviate alcoholic liver disease at low doses by regulating the intestinal Fxr-Fgf15 signaling pathway and bile acid homeostasis, but high doses can cause hepatotoxicity. N-acetylcysteine (NAC), as a glutathione precursor, can improve some liver function indicators such as albumin and bilirubin, but its effects on major liver enzymes (AST, ALT, ALP) are inconsistent, resulting in limited clinical efficacy. Summary of the Invention
[0004] In view of the shortcomings of the prior art, the present invention provides an ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex to improve alcoholic hepatitis, the purpose of which is to solve the problems mentioned in the background art.
[0005] In a first aspect, the present invention provides an ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex for improving alcoholic hepatitis, wherein the ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex is composed of ovotransferrin, nervonic acid and Gynostemma pentaphyllum extract, and the mass ratio of ovotransferrin:nervonic acid:Gynostemma pentaphyllum extract is 10-30:5-15:20-40.
[0006] Furthermore, by mass ratio, ovotransferrin: nervonic acid: Gynostemma pentaphyllum extract = 20: 15: 40.
[0007] Furthermore, the active ingredient of the Gynostemma pentaphyllum extract is Gynostemma pentaphyllum saponin.
[0008] Furthermore, the preparation method of the Gynostemma pentaphyllum extract specifically includes the following steps: take the whole herb of Gynostemma pentaphyllum, crush it, extract it by reflux with 70% ethanol, reflux extract twice, combine the extracts, concentrate under reduced pressure, purify it through macroporous adsorption resin, collect the Gynostemma pentaphyllum saponin enriched fraction, concentrate and dry it to obtain the Gynostemma pentaphyllum extract.
[0009] Furthermore, the ratio of whole Gynostemma pentaphyllum herb to 70% ethanol was 1g:12mL.
[0010] Furthermore, the reflux extraction temperature is 85°C, and the reflux extraction time is 2 hours.
[0011] Secondly, the present invention provides the use of an ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex that improves alcoholic hepatitis in the preparation of a medicament for treating alcoholic hepatitis.
[0012] Furthermore, the drug is formulated into clinically acceptable tablets, pills, capsules, suspensions, gels, solutions, emulsions, ointments, or lotions.
[0013] Furthermore, the drug also includes pharmaceutically acceptable excipients.
[0014] Furthermore, the excipients include microcrystalline cellulose, sodium carboxymethyl starch, or magnesium stearate.
[0015] The present invention has the following beneficial effects: (1) The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex reduces liver enlargement, liver vacuolar changes and increased liver lipid droplets caused by alcoholic hepatitis.
[0016] (2) The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex contains three core active ingredients, each with specific physicochemical properties and biological activities to synergistically improve alcoholic hepatitis. Ovotransferrin not only reduces iron-catalyzed oxidative stress by regulating iron homeostasis, but also exhibits immunomodulatory and antibacterial activities, which can reduce liver inflammation caused by endotoxin translocation. Its isoelectric point is about pH=6.5, which maintains structural stability in an acidic environment and is conducive to maintaining activity in the gastrointestinal environment. As a cell membrane component, nervonic acid can integrate into the hepatocyte membrane, enhance membrane stability, and reduce changes in membrane fluidity caused by ethanol. At the same time, as a nuclear receptor activator, nervonic acid can regulate the FXR and Nrf2 signaling pathways, affect bile acid metabolism and antioxidant response, and its hydrophobic properties help improve the bioavailability of other components. Gynostemma pentaphyllum extract (Gynostemma pentaphyllum saponin content ≥80%) has an amphiphilic structure, containing a hydrophobic triterpenoid skeleton and a hydrophilic glycosyl group, which enables it to interact with the cell membrane and regulate membrane receptor function. Attached Figure Description
[0017] Exemplary embodiments of the present invention can be more fully understood by referring to the following figures: Figure 1 This is a stained image of a liver section from Embodiment 3 of the present invention.
[0018] Figure 2 This is a statistical chart of liver index in Embodiment 3 of the present invention, where different letters represent statistical differences.
[0019] Figure 3 This is a statistical chart of ALT (alanine aminotransferase) in Example 3 of the present invention, where different letters represent statistical differences.
[0020] Figure 4 This is the AST (aspartate aminotransferase) statistical chart of Example 3 of the present invention, where different letters represent statistical differences. Detailed Implementation
[0021] To make the technical problems to be solved, the technical solutions, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.
[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains; the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the invention.
[0023] This invention provides an ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex for improving alcoholic hepatitis. The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex is composed of ovotransferrin, nervonic acid and Gynostemma pentaphyllum extract, with a mass ratio of ovotransferrin:nervonic acid:Gynostemma pentaphyllum extract = 10-30: 5-15: 20-40.
[0024] In some embodiments, the ratio of ovotransferrin: nervonic acid: Gynostemma pentaphyllum extract is 20:15:40 by mass.
[0025] In some embodiments, the active ingredient in Gynostemma pentaphyllum extract is gypenosides.
[0026] In some embodiments, the preparation method of Gynostemma pentaphyllum extract specifically includes the following steps: take the whole herb of Gynostemma pentaphyllum, crush it, extract it by reflux with 70% ethanol, reflux extract twice, combine the extracts, concentrate under reduced pressure, purify it through macroporous adsorption resin, collect the Gynostemma pentaphyllum saponin enriched fraction, concentrate and dry it to obtain Gynostemma pentaphyllum extract.
[0027] In some embodiments, the ratio of whole Gynostemma pentaphyllum herb to 70% ethanol is 1g:12mL.
[0028] In some embodiments, the reflux extraction temperature is 85°C and the reflux extraction time is 2 hours.
[0029] In some embodiments, the present invention provides the use of an ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex that improves alcoholic hepatitis in the preparation of a medicament for treating alcoholic hepatitis.
[0030] In some embodiments, the drug is formulated as a clinically acceptable tablet, pill, capsule, suspension, gel, solution, emulsion, ointment, or lotion.
[0031] In some embodiments, the medicament may also include pharmaceutically acceptable excipients.
[0032] In some embodiments, the excipients include microcrystalline cellulose, sodium carboxymethyl starch, or magnesium stearate.
[0033] Example 1: Preparation of Gynostemma pentaphyllum extract One kg of dried Gynostemma pentaphyllum whole herb was crushed and passed through a 40-mesh sieve. It was extracted twice with 70% ethanol solution at a material-to-liquid ratio of 1 g:12 mL under reflux at 85℃ for 2 hours. The extracts were combined, filtered, and the ethanol was recovered under reduced pressure. The extract was concentrated to a paste. The paste was dissolved in water to a concentration of 1 g / mL (based on crude drug concentration) and loaded onto a pretreated AB-8 macroporous adsorption resin column (2 L column volume). Elution was first performed with 3 column volumes of dewatering solution, then with 5 column volumes of 50% ethanol, and finally with 4 column volumes of 70% ethanol. The 70% ethanol eluent was collected, concentrated under reduced pressure, and spray-dried to obtain 125 g of Gynostemma pentaphyllum extract. HPLC analysis showed that the Gynostemma pentaphyllum saponin content was 82.3%.
[0034] Example 2: Preparation of ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex (1) Weigh out ovotransferrin, nervonic acid and Gynostemma pentaphyllum extract according to formulas A, B and C, put them into a three-dimensional motion mixer, set the speed to 25 r / min, mix for 30 minutes, and after mixing evenly, pass through an 80-mesh sieve to obtain ovotransferrin-nervonic acid-Gynostemma pentaphyllum compound. Formula A: ovotransferrin: nervonic acid: gynostemma pentaphyllum extract = 10:5:20. Weigh out 78.57g of ovotransferrin, 39.29g of nervonic acid, and 157.14g of gynostemma pentaphyllum extract according to this ratio. Formula B: Ovotransferrin : Nervonic acid : Gynostemma pentaphyllum extract = 15 : 10 : 30. Weigh out 75.00g of ovotransferrin, 50.00g of nervonic acid, and 150.00g of Gynostemma pentaphyllum extract according to this ratio. Formula C: ovotransferrin: nervonic acid: gynostemma pentaphyllum extract = 20:15:40. Weigh out 73.33g of ovotransferrin, 55.00g of nervonic acid, and 146.67g of gynostemma pentaphyllum extract according to this ratio. (2) Add the ovotransferrin-nervonic acid-Gynostemma pentaphyllum compound of each formulation to the excipients (150g microcrystalline cellulose, 60g sodium carboxymethyl starch and 15g magnesium stearate), mix evenly and compress into tablets, each tablet weighing 500mg and containing 275mg of active ingredient.
[0035] Example 3: Effects of ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex on a mouse model of alcoholic hepatitis (1) Animal model establishment: 90 healthy C57 female mice weighing 20-22g were randomly divided into 9 groups: normal control group, model control group, oval transferrin control group (250mg / kg), nervonic acid control group (250mg / kg), Gynostemma pentaphyllum extract control group (250mg / kg), silymarin positive control group (100mg / kg) and three experimental groups (formulas A, B and C in Example 2 were administered by gavage at 250mg / kg).
[0036] Except for the normal control group, the other groups adopted the NIAAA alcoholic liver injury model: they were first given Lieber-DeCarli liquid diet for 5 days to adapt, followed by Lieber-DeCarli liquid diet containing 5% (v / v) ethanol for 10 consecutive days. After the last Lieber-DeCarli liquid diet containing 5% ethanol was given, ethanol was administered by gavage (5g / kg body weight). The normal control group was given an isocaloric control liquid diet and maltodextrin by gavage.
[0037] (2) Administration method: The ovotransferrin control group, nervonic acid control group, Gynostemma pentaphyllum extract control group, silymarin positive control group and three experimental groups were given the corresponding drugs by gavage once a day at the same time as the model was established. The normal control group and the model control group were given the same volume of physiological saline by gavage.
[0038] (3) Detection indicators: The liver was photographed and the liver index was calculated; a portion of liver tissue was fixed with 4% paraformaldehyde, embedded in paraffin, and pathological changes were observed.
[0039] Results of changes in liver health status in each group are as follows: Figures 1-4 As shown, the results indicated that compared with the model control group, all three experimental groups (formulas A, B, and C) reduced hepatomegaly, vacuolar changes in the liver, and increased lipid droplets in the liver caused by alcoholic hepatitis. The experimental group (formula C, ovotransferrin: nervonic acid: Gynostemma pentaphyllum extract = 20:15:40) showed the most significant reduction. Figure 1 Furthermore, the liver indices of the three experimental groups were close to those of the normal control group. Figure 2 The three experimental groups showed no significant differences in ALT (alanine aminotransferase) and AST (aspartate aminotransferase), the core serological indicators reflecting the degree of hepatocyte damage, compared with the normal control group. This indicates that the ovotransferrin-nervonic acid-Gynostemma pentaphyllum compound can improve alcoholic hepatitis, especially the ovotransferrin:nervonic acid:Gynostemma pentaphyllum extract = 20:15:40, which has the best effect.
[0040] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. Ovotransferrin - nervonic acid - gynostemma complex for improving alcoholic hepatitis, characterized in that, The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex is composed of ovotransferrin, nervonic acid and Gynostemma pentaphyllum extract, with a mass ratio of ovotransferrin:nervonic acid:Gynostemma pentaphyllum extract = 10-30: 5-15: 20-40.
2. The Ovotransferrin-Glycerol Monocaprylate-Gynostemma pentaphyllum formulation for improving alcoholic hepatitis according to claim 1, wherein By mass ratio, ovotransferrin: nervonic acid: Gynostemma pentaphyllum extract = 20: 15:
40.
3. The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex for improving alcoholic hepatitis as described in claim 1, characterized in that, The active ingredient in the Gynostemma pentaphyllum extract is Gynostemma pentaphyllum saponin.
4. The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex for improving alcoholic hepatitis as described in claim 3, characterized in that, The preparation method of the Gynostemma pentaphyllum extract is as follows: take the whole herb of Gynostemma pentaphyllum, crush it, extract it by reflux with 70% ethanol, reflux extract twice, combine the extracts, concentrate under reduced pressure, purify it through macroporous adsorption resin, collect the Gynostemma pentaphyllum saponin enriched fraction, concentrate and dry it to obtain the Gynostemma pentaphyllum extract.
5. The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex for improving alcoholic hepatitis as described in claim 4, characterized in that, The ratio of whole Gynostemma pentaphyllum herb to 70% ethanol is 1g:12mL.
6. The ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex for improving alcoholic hepatitis as described in claim 5, characterized in that, The reflux extraction temperature is 85°C, and the reflux extraction time is 2 hours.
7. The use of the ovotransferrin-nervonic acid-Gynostemma pentaphyllum complex as described in any one of claims 1-6 in the preparation of a medicament for treating alcoholic hepatitis.
8. The application as described in claim 7, characterized in that, The drug is formulated as a clinically acceptable tablet, pill, capsule, suspension, gel, solution, emulsion, ointment, or lotion.
9. The application as described in claim 8, characterized in that, The drug also includes pharmaceutically acceptable excipients.
10. The application as described in claim 9, characterized in that, The excipients include microcrystalline cellulose, sodium carboxymethyl starch, or magnesium stearate.