A natural plant liver-protecting formulation based on promoting bile secretion and a preparation thereof

Abstract

The present invention discloses a natural plant liver-protecting formulation based on promoting bile secretion and a preparation thereof, relating to the technical field of natural plant medicine and health food. The present invention effectively achieves a liver-protecting effect through multi-target synergistic actions of promoting bile secretion, cholagogic and detoxifying effects, and directly protecting liver cells. Among these, the milk thistle extract is rich in silymarin, which can stabilize hepatocyte membranes, prevent toxic substances from entering hepatocytes, and promote the repair and regeneration of damaged hepatocytes. Cynarin in the artichoke extract promotes bile secretion, accelerates the excretion of toxins and waste from the body, and reduces the burden on the liver. The total flavonoids component in the dandelion root extract has anti-inflammatory and antioxidant effects, which can protect hepatocytes from free radical damage, thereby comprehensively improving liver health.

Description

[0001] DESCRIPTION

[0002] A natural plant liver-protecting formulation based on promoting bile secretion and a preparation thereof TECHNICAL FIELD

[0003] The present invention relates to the technical field of natural plant medicine and health food, specifically to a natural plant liver-protecting formulation based on promoting bile secretion and a preparation thereof. BACKGROUND

[0004] In modern society, with the accelerated pace of life and increased environmental pollution, liver health issues are receiving increasing attention. As an important detoxification organ of the human body, the liver undertakes various physiological functions such as metabolism, detoxification, and energy storage. However, factors such as poor lifestyle habits, environmental pollution, and side effects of drugs often increase the burden on the liver, thereby leading to a series of liver diseases.

[0005] Although various liver-protecting products exist on the market, traditional technologies often have some limitations. First, many liver-protecting products rely on a single component or a single mechanism of action, making it difficult to achieve a comprehensive liver-protecting effect. For example, some products may focus only on detoxification or only on antioxidation, neglecting that liver health requires multifaceted protection. Second, some liver-protecting products may contain chemically synthesized ingredients, and long-term use may bring certain side effects or dependence. Furthermore, the preparation process of traditional liver-protecting products may be relatively complex, leading to higher costs and difficulty in popularization. More importantly, many traditional liver-protecting products lack scientific validation, and their liver-protecting efficacy and safety are difficult to guarantee.

[0006] In view of the limitations of traditional liver-protecting technologies, the present invention proposes a natural plant liver-protecting formulation based on promoting bile secretion and a preparation thereof, which is particularly important.

[0007] SUMMARY

[0008] An objective of the present invention is to address the shortcomings of the prior art by providing a natural plant liver-protecting formulation based on promoting bile secretion and a preparation thereof. It can achieve multi-target synergistic actions of promoting bile secretion, cholagogic and detoxifying effects, and directly protecting liver cells through the scientific proportioning of milk thistle extract, artichoke extract, and dandelion root extract, thereby effectively enhancing the liver-protecting effect. At the same time, the active ingredients in the formulation, such as silymarin, cynarin, and total flavonoids, all possess significant antioxidant effects, capable of neutralizing excess free radicals in the body and reducing oxidative stress damage to hepatocytes. Furthermore, the preparation method of the present invention is simple and easy to implement with low cost, and the selected raw materials are all natural plant extracts with high safety, suitable for long-term administration.

[0009] To solve the above technical problems, the present invention provides the following technical solutions: A natural plant liver-protecting formulation based on promoting bile secretion, prepared from the following raw materials in parts by weight:

[0010] The active ingredients of the formulation consist of milk thistle extract, artichoke extract, and dandelion root extract; the formulation achieves the core functions of liver protection and antioxidation through the multi-target synergistic actions of promoting bile secretion, cholagogic and detoxifying effects, and hepatocyte protection.

[0011] Further, in terms of dry parts by weight, the amounts of the active ingredients are: 10-60 parts of milk thistle extract, 20-70 parts of artichoke extract, and 10-50 parts of dandelion root extract.

[0012] Furthermore, in terms of dry parts by weight, the amounts of the active ingredients are: 20-50 parts of milk thistle extract, 30-60 parts of artichoke extract, and 20-40 parts of dandelion root extract.

[0013] Furthermore, in terms of dry parts by weight, the active ingredients consist of 30 parts of milk thistle extract, 45 parts of artichoke extract, and 25 parts of dandelion root extract.

[0014] Furthermore, the mass content of cynarin in the artichoke extract is >2.5%; the mass content of silymarin in the milk thistle extract is >80%; the mass content of total flavonoids in the dandelion root extract is >4%.

[0015] Furthermore, the formulation further comprises pharmaceutically or health food acceptable excipients, the mass of the excipients accounting for 10%-90% of the total mass of the formulation.

[0016] Furthermore, the excipients are selected from one or more of fillers, disintegrants, lubricants, binders, and glidants; the dosage form of the formulation is an oral preparation, specifically any one of tablets, hard capsules, granules, powders, and pills.

[0017] In another aspect, a preparation of a natural plant liver-protecting formulation based on promoting bile secretion, characterized in that the preparation method comprises the following steps:

[0018] SI . Raw material pretreatment: respectively taking dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after impurity removal, cleaning, drying, and grinding, respectively obtaining powders of each raw material;

[0019] 52. Extract preparation: respectively subjecting each raw material powder to extraction, solid-liquid separation, concentration, and drying to obtain milk thistle extract, artichoke extract, and dandelion root extract;

[0020] 53. Weighing and mixing: weighing each extract according to the formula ratio, adding optional excipients, and placing in mixing equipment for thorough mixing to obtain a mixed powder material;

[0021] 54. Formulation forming: preparing the mixed powder material into the corresponding dosage form to obtain the natural plant liver-protecting formulation.

[0022] Furthermore, the preparation process for each extract in step S2 is specifically as follows: Preparation of the artichoke extract: using artichoke leaf powder as raw material, using 50%-70% ethanol aqueous solution as extraction solvent, solid-liquid ratio 1:10-1 :20, reflux extraction 2-3 times, each time for 1-2 h, combining the extracts, concentrating under reduced pressure to a clear paste with a relative density of 1.10-1.20 at 60°C, and obtaining by spray drying; Preparation of the milk thistle extract: using defatted milk thistle seed meal powder as raw material, using 60%-80% ethanol aqueous solution as extraction solvent, solid-liquid ratio 1:8-1 :15, reflux extraction 2-3 times, each time for 1.5-2.5 h, combining the extracts, and obtaining by concentration under reduced pressure, defatting, purification, and spray drying; Preparation of the dandelion root extract: using dandelion root powder as raw material, using 40%-60% ethanol aqueous solution as extraction solvent, solid-liquid ratio 1:10-1 :20, reflux extraction 2-3 times, each time for 1-2 h, combining the extracts, concentrating under reduced pressure to a clear paste with a relative density of 1.10-1.15 at 60 °C, and obtaining by spray drying.

[0023] Compared with the prior art, this natural plant liver-protecting formulation based on promoting bile secretion and its preparation have the following beneficial effects:

[0024] I. The natural plant liver-protecting formulation of the present invention effectively achieves a liver-protecting effect through multi-target synergistic actions of promoting bile secretion, cholagogic and detoxifying effects, and directly protecting liver cells. Among these, the milk thistle extract is rich in silymarin, which can stabilize hepatocyte membranes, prevent toxic substances from entering hepatocytes, and promote the repair and regeneration of damaged hepatocytes. Cynarin in the artichoke extract promotes bile secretion, accelerates the excretion of toxins and waste from the body, and reduces the burden on the liver. The total flavonoids component in the dandelion root extract has anti-inflammatory and antioxidant effects, which can protect hepatocytes from free radical damage, thereby comprehensively improving liver health.

[0025] II. The liver-protecting formulation of the present invention also possesses significant antioxidant effects. Active ingredients such as silymarin, cynarin, and the total flavonoids in dandelion root extract are potent free radical scavengers, capable of effectively neutralizing excess free radicals in the body and reducing oxidative stress damage to hepatocytes. The combined action of these components not only protects the structural and functional integrity of hepatocytes but also delays the aging process of the liver. Long-term administration helps maintain the liver's youthful state and efficient metabolic capacity.

[0026] Other advantages, objectives, and features of the present invention will be set forth in part in the following description, and in part will become apparent to those skilled in the art upon examination of the following or may be learned from practice of the invention.

[0027] BRIEF DESCRIPTION OF DRAWINGS

[0028] To explain the technical solutions in the embodiments of the present invention or the prior art more clearly, the following briefly introduces the drawings required for describing the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without inventive effort.

[0029] Figure 1 is a flow chart of the natural plant liver-protecting formulation based on promoting bile secretion and the preparation thereof.

[0030] DETAILED DESCRIPTION

[0031] To further elaborate on the technical means and effects adopted by the present invention to achieve the intended invention objectives, the following, in conjunction with the accompanying drawings and preferred embodiments, provides a detailed description of the specific implementation, structure, features, and effects of the present invention.

[0032] Embodiments 1 to 3 only change the content of milk thistle extract

[0033] Embodiment 1 I. Formulation Formula

[0034] (I) Core Formula of Active Ingredients (in dry parts by weight)

[0035] Milk thistle extract 20 parts, Artichoke extract 45 parts, Dandelion root extract 25 parts. Total parts by weight of active ingredients: 90 parts.

[0036] (II) Excipient Formula

[0037] The total mass of the formulation in this embodiment is 1900 g, wherein the total mass of active ingredients is 900 g, the total mass of excipients is 1000 g, and the excipients account for 52.6% of the total mass of the formulation, meeting the usage requirement of 10%-90%. The specific composition of excipients is as follows: microcrystalline cellulose (filler) 820 g, crospovidone (disintegrant) 150 g, silicon dioxide (glidant) 20 g, magnesium stearate (lubricant) 10 g.

[0038] (III) Raw Material Quality Control Standards

[0039] Artichoke extract: mass content of cynarin is 3.2%, meeting the requirement of >2.5%; Milk thistle extract: mass content of silymarin is 83.5%, meeting the requirement of >80%; Dandelion root extract: mass content of total flavonoids is 4.8%, meeting the requirement of >4%.

[0040] IE Formulation Preparation Method

[0041] 51 Raw material pretreatment

[0042] Respectively take dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after air separation for impurity removal, washing with purified water, drying with hot air at 60 °C to a moisture content of <8%, respectively grind using a universal grinder and pass through a 40-mesh sieve to obtain defatted milk thistle seed meal powder, artichoke leaf powder, and dandelion root powder, seal for later use.

[0043] 52 Extract preparation

[0044] (1) Preparation of artichoke extract: Take artichoke leaf powder, use 60% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.15 at 60°C, obtain artichoke extract powder by spray drying, seal for later use. (2) Preparation of milk thistle extract: Take defatted milk thistle seed meal powder, use 70% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:10, heat and reflux extract twice, each time for 2 h; combine the two extracts, concentrate under vacuum and reduced pressure until no alcohol odor remains, defat with petroleum ether, purify with macroporous adsorption resin, concentrate the eluate under reduced pressure and then spray dry to obtain milk thistle extract powder, seal for later use. (3) Preparation of dandelion root extract: Take dandelion root powder, use 50% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.12 at 60 °C, obtain dandelion root extract powder by spray drying, seal for later use.

[0045] 53 Weighing and mixing

[0046] Accurately weigh according to the formula ratio 200 g of the milk thistle extract prepared above, 450 g of artichoke extract, and 250 g of dandelion root extract. Then accurately weigh according to the excipient formula 820 g of microcrystalline cellulose, 150 g of crospovidone, and 20 g of silicon dioxide, place them in a three-dimensional motion mixer and mix for 30 min until the materials are uniform; finally add 10 g of magnesium stearate, supplement mixing for 5 min to obtain a uniform mixed powder material, sample and test content uniformity, set aside after passing.

[0047] 54 Formulation forming

[0048] Use a fully automatic hard capsule filling machine to fill the above mixed powder material into size 0 hard gelatin capsules at a filling weight of 0.4 g per capsule. After polishing, full inspection, inner packaging, and outer packaging, obtain the natural plant liver-protecting hard capsule formulation based on promoting bile secretion.

[0049] This formulation can inhibit lipid peroxidation damage in liver tissue and repair the body's endogenous antioxidant defense system, thereby achieving antioxidation and blocking the progression of chronic liver injury mediated by oxidative stress. Aiming at the problems of peroxide product accumulation and decreased antioxidant enzyme activity in the state of liver injury, high-dose administration can very significantly reduce the content of MDA, the end product of lipid peroxidation in liver tissue, by 51.27% compared to the liver injury model group, while very significantly increasing the activities of the core endogenous antioxidant enzymes SOD and GSH-Px by 98.62% and 112.35%, respectively, compared to the model group. The overall antioxidant capacity of the body is restored to over 88% of the level of normal rats, an effect comparable to commercially available silymarin preparations, reducing the continuous attack of oxidative stress on hepatocytes at the source and building a solid antioxidant protective barrier for hepatocytes.

[0050] Embodiment 2

[0051] I. Formulation Formula

[0052] (I) Core Formula of Active Ingredients (in dry parts by weight)

[0053] Milk thistle extract 40 parts, Artichoke extract 45 parts, Dandelion root extract 25 parts. Total parts by weight of active ingredients: 110 parts.

[0054] (II) Excipient Formula

[0055] The total mass of the formulation in this embodiment is 2100 g, wherein the total mass of active ingredients is 1100 g, the total mass of excipients is 1000 g, and the excipients account for 47.6% of the total mass of the formulation, meeting the usage requirement of 10%-90%. The specific composition of excipients is as follows: microcrystalline cellulose (filler) 820 g, crospovidone (disintegrant) 150 g, silicon dioxide (glidant) 20 g, magnesium stearate (lubricant) 10 g.

[0056] (III) Raw Material Quality Control Standards Artichoke extract: mass content of cynarin is 3.2%, meeting the requirement of >2.5%; Milk thistle extract: mass content of silymarin is 83.5%, meeting the requirement of >80%; Dandelion root extract: mass content of total flavonoids is 4.8%, meeting the requirement of >4%.

[0057] II. Formulation Preparation Method

[0058] 51 Raw material pretreatment

[0059] Respectively take dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after air separation for impurity removal, washing with purified water, drying with hot air at 60 °C to a moisture content of <8%, respectively grind using a universal grinder and pass through a 40-mesh sieve to obtain defatted milk thistle seed meal powder, artichoke leaf powder, and dandelion root powder, seal for later use.

[0060] 52 Extract preparation

[0061] (1) Preparation of artichoke extract: Take artichoke leaf powder, use 60% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.15 at 60°C, obtain artichoke extract powder by spray drying, seal for later use. (2) Preparation of milk thistle extract: Take defatted milk thistle seed meal powder, use 70% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:10, heat and reflux extract twice, each time for 2 h; combine the two extracts, concentrate under vacuum and reduced pressure until no alcohol odor remains, defat with petroleum ether, purify with macroporous adsorption resin, concentrate the eluate under reduced pressure and then spray dry to obtain milk thistle extract powder, seal for later use. (3) Preparation of dandelion root extract: Take dandelion root powder, use 50% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under io vacuum and reduced pressure to a clear paste with a relative density of 1.12 at 60 °C, obtain dandelion root extract powder by spray drying, seal for later use.

[0062] 53 Weighing and mixing

[0063] Accurately weigh according to the formula ratio 400 g of the milk thistle extract prepared above, 450 g of artichoke extract, and 250 g of dandelion root extract. Then accurately weigh according to the excipient formula 820 g of microcrystalline cellulose, 150 g of crospovidone, and 20 g of silicon dioxide, place them in a three-dimensional motion mixer and mix for 30 min until the materials are uniform; finally add 10 g of magnesium stearate, supplement mixing for 5 min to obtain a uniform mixed powder material, sample and test content uniformity, set aside after passing.

[0064] 54 Formulation forming

[0065] Use a fully automatic hard capsule filling machine to fill the above mixed powder material into size 0 hard gelatin capsules at a filling weight of 0.4 g per capsule. After polishing, full inspection, inner packaging, and outer packaging, obtain the natural plant liver-protecting hard capsule formulation based on promoting bile secretion.

[0066] This formulation can inhibit lipid peroxidation damage in liver tissue and repair the body's endogenous antioxidant defense system, thereby achieving potent antioxidation and blocking the progression of chronic liver injury mediated by oxidative stress. Aiming at the problems of peroxide product accumulation and collapse of antioxidant enzyme activity in the state of liver injury, high-dose administration can very significantly reduce the content of MDA, the end product of lipid peroxidation in liver tissue, by 63.89% compared to the liver injury model group, while very significantly increasing the activities of the core endogenous antioxidant enzymes SOD and GSH-Px by 128.74% and 148.62%, respectively, compared to the model group. The overall antioxidant capacity of the body is restored to over 96% of the level of normal rats, an effect significantly superior to commercially available ii silymarin preparations, reducing the continuous attack of oxidative stress on hepatocytes at the source and building a solid antioxidant protective barrier for hepatocytes.

[0067] Embodiment 3

[0068] I. Formulation Formula

[0069] (I) Core Formula of Active Ingredients (in dry parts by weight)

[0070] Milk thistle extract 50 parts, Artichoke extract 45 parts, Dandelion root extract 25 parts. Total parts by weight of active ingredients: 120 parts.

[0071] (II) Excipient Formula

[0072] The total mass of the formulation in this embodiment is 2200 g, wherein the total mass of active ingredients is 1200 g, the total mass of excipients is 1000 g, and the excipients account for 45.5% of the total mass of the formulation, meeting the usage requirement of 10%-90%. The specific composition of excipients is as follows: microcrystalline cellulose (filler) 820 g, crospovidone (disintegrant) 150 g, silicon dioxide (glidant) 20 g, magnesium stearate (lubricant) 10 g.

[0073] (III) Raw Material Quality Control Standards

[0074] Artichoke extract: mass content of cynarin is 3.2%, meeting the requirement of >2.5%; Milk thistle extract: mass content of silymarin is 83.5%, meeting the requirement of >80%; Dandelion root extract: mass content of total flavonoids is 4.8%, meeting the requirement of >4%.

[0075] IE Formulation Preparation Method

[0076] S 1 Raw material pretreatment

[0077] Respectively take dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after air separation for impurity removal, washing with purified water, drying with hot air at 60 °C to a moisture content of <8%, respectively grind using a universal grinder and pass through a 40-mesh sieve to obtain defatted milk thistle seed meal powder, artichoke leaf powder, and dandelion root powder, seal for later use. 52 Extract preparation

[0078] (1) Preparation of artichoke extract: Take artichoke leaf powder, use 60% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.15 at 60°C, obtain artichoke extract powder by spray drying, seal for later use. (2) Preparation of milk thistle extract: Take defatted milk thistle seed meal powder, use 70% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:10, heat and reflux extract twice, each time for 2 h; combine the two extracts, concentrate under vacuum and reduced pressure until no alcohol odor remains, defat with petroleum ether, purify with macroporous adsorption resin, concentrate the eluate under reduced pressure and then spray dry to obtain milk thistle extract powder, seal for later use. (3) Preparation of dandelion root extract: Take dandelion root powder, use 50% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.12 at 60 °C, obtain dandelion root extract powder by spray drying, seal for later use.

[0079] 53 Weighing and mixing

[0080] Accurately weigh according to the formula ratio 500 g of the milk thistle extract prepared above, 450 g of artichoke extract, and 250 g of dandelion root extract. Then accurately weigh according to the excipient formula 820 g of microcrystalline cellulose, 150 g of crospovidone, and 20 g of silicon dioxide, place them in a three-dimensional motion mixer and mix for 30 min until the materials are uniform; finally add 10 g of magnesium stearate, supplement mixing for 5 min to obtain a uniform mixed powder material, sample and test content uniformity, set aside after passing.

[0081] S4 Formulation forming Use a fully automatic hard capsule filling machine to fill the above mixed powder material into size 0 hard gelatin capsules at a filling weight of 0.4 g per capsule. After polishing, full inspection, inner packaging, and outer packaging, obtain the natural plant liver-protecting hard capsule formulation based on promoting bile secretion.

[0082] This formulation can inhibit lipid peroxidation damage in liver tissue and repair the body's endogenous antioxidant defense system, thereby achieving potent antioxidation and blocking the progression of chronic liver injury mediated by oxidative stress. Aiming at the problems of peroxide product accumulation and collapse of antioxidant enzyme activity in the state of liver injury, high-dose administration can very significantly reduce the content of MDA, the end product of lipid peroxidation in liver tissue, by 68.17% compared to the liver injury model group, while very significantly increasing the activities of the core endogenous antioxidant enzymes SOD and GSH-Px by 141.53% and 162.48%, respectively, compared to the model group. The overall antioxidant capacity of the body is restored to over 98% of the level of normal rats, an effect extremely significantly superior to commercially available silymarin preparations, reducing the continuous attack of oxidative stress on hepatocytes at the source and building a solid antioxidant protective barrier for hepatocytes.

[0083] Embodiments 4 to 6 only change the content of dandelion root extract

[0084] Embodiment 4

[0085] I. Formulation Formula

[0086] (I) Core Formula of Active Ingredients (in dry parts by weight)

[0087] Milk thistle extract 30 parts, Artichoke extract 45 parts, Dandelion root extract 15 parts. Total parts by weight of active ingredients: 90 parts.

[0088] (II) Excipient Formula The total mass of the formulation in this embodiment is 1900 g, wherein the total mass of active ingredients is 900 g, the total mass of excipients is 1000 g, and the excipients account for 52.6% of the total mass of the formulation, meeting the usage requirement of 10%-90%. The specific composition of excipients is as follows: microcrystalline cellulose (filler) 820 g, crospovidone (disintegrant) 150 g, silicon dioxide (glidant) 20 g, magnesium stearate (lubricant) 10 g.

[0089] (Ill) Raw Material Quality Control Standards Artichoke extract: mass content of cynarin is 3.2%, meeting the requirement of >2.5%; Milk thistle extract: mass content of silymarin is 83.5%, meeting the requirement of >80%; Dandelion root extract: mass content of total flavonoids is 4.8%, meeting the requirement of >4%.

[0090] II. Formulation Preparation Method

[0091] 51 Raw material pretreatment Respectively take dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after air separation for impurity removal, washing with purified water, drying with hot air at 60 °C to a moisture content of <8%, respectively grind using a universal grinder and pass through a 40-mesh sieve to obtain defatted milk thistle seed meal powder, artichoke leaf powder, and dandelion root powder, seal for later use.

[0092] 52 Extract preparation (1) Preparation of artichoke extract: Take artichoke leaf powder, use 60% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.15 at 60°C, obtain artichoke extract powder by spray drying, seal for later use. (2) Preparation of milk thistle extract: Take defatted milk thistle seed meal powder, use 70% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:10, heat and reflux extract twice, each time for 2 h; combine the two extracts, concentrate under vacuum and reduced pressure until no alcohol odor remains, defat with petroleum ether, purify with macroporous adsorption resin, concentrate the eluate under reduced pressure and then spray dry to obtain milk thistle extract powder, seal for later use. (3) Preparation of dandelion root extract: Take dandelion root powder, use 50% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.12 at 60°C, obtain dandelion root extract powder by spray drying, seal for later use.

[0093] 53 Weighing and mixing Accurately weigh according to the formula ratio 300 g of the milk thistle extract prepared above, 450 g of artichoke extract, and 150 g of dandelion root extract. Then accurately weigh according to the excipient formula 820 g of microcrystalline cellulose, 150 g of crospovidone, and 20 g of silicon dioxide, place them in a three-dimensional motion mixer and mix for 30 min until the materials are uniform; finally add 10 g of magnesium stearate, supplement mixing for 5 min to obtain a uniform mixed powder material, sample and test content uniformity, set aside after passing.

[0094] 54 Formulation forming Use a fully automatic hard capsule filling machine to fill the above mixed powder material into size 0 hard gelatin capsules at a filling weight of 0.4 g per capsule. After polishing, full inspection, inner packaging, and outer packaging, obtain the natural plant liver-protecting hard capsule formulation based on promoting bile secretion.

[0095] Through the scientific combination of milk thistle extract, artichoke extract, and dandelion root extract, this formulation compensates for the limitations of single silymarin which can only target hepatocyte protection and cannot achieve cholagogic and detoxifying effects, achieving the multi-target synergistic liver-protecting action of cholagogic and detoxifying effects + hepatocyte protection + antioxidation. High-dose administration can increase the 4h cumulative bile flow in liver-injured rats by 52.78% compared to the model group, decrease serum alanine aminotransferase ALT by 62.35% compared to the model group, and decrease the content of MDA, the end product of lipid peroxidation in liver tissue, by 53.47% compared to the model group. The core efficacy indicators are comparable to commercially available mainstream silymarin liver-protecting preparations. At the same time, all active ingredients are derived from natural plants, and while achieving basic liver-protecting efficacy, they possess good administration safety and tolerability, adaptable to the usage needs of daily mild liver protection.

[0096] Embodiment 5

[0097] I. Formulation Formula

[0098] (I) Core Formula of Active Ingredients (in dry parts by weight)

[0099] Milk thistle extract 30 parts, Artichoke extract 45 parts, Dandelion root extract 35 parts. Total parts by weight of active ingredients: 110 parts.

[0100] (II) Excipient Formula The total mass of the formulation in this embodiment is 2100 g, wherein the total mass of active ingredients is 1100 g, the total mass of excipients is 1000 g, and the excipients account for 47.6% of the total mass of the formulation, meeting the usage requirement of 10%-90%. The specific composition of excipients is as follows: microcrystalline cellulose (filler) 820 g, crospovidone (disintegrant) 150 g, silicon dioxide (glidant) 20 g, magnesium stearate (lubricant) 10 g.

[0101] (III) Raw Material Quality Control Standards Artichoke extract: mass content of cynarin is 3.2%, meeting the requirement of >2.5%; Milk thistle extract: mass content of silymarin is 83.5%, meeting the requirement of >80%; Dandelion root extract: mass content of total flavonoids is 4.8%, meeting the requirement of >4%.

[0102] IE Formulation Preparation Method

[0103] SI Raw material pretreatment Respectively take dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after air separation for impurity removal, washing with purified water, drying with hot air at 60 °C to a moisture content of <8%, respectively grind using a universal grinder and pass through a 40-mesh sieve to obtain defatted milk thistle seed meal powder, artichoke leaf powder, and dandelion root powder, seal for later use.

[0104] 52 Extract preparation (1) Preparation of artichoke extract: Take artichoke leaf powder, use 60% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.15 at 60°C, obtain artichoke extract powder by spray drying, seal for later use. (2) Preparation of milk thistle extract: Take defatted milk thistle seed meal powder, use 70% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:10, heat and reflux extract twice, each time for 2 h; combine the two extracts, concentrate under vacuum and reduced pressure until no alcohol odor remains, defat with petroleum ether, purify with macroporous adsorption resin, concentrate the eluate under reduced pressure and then spray dry to obtain milk thistle extract powder, seal for later use. (3) Preparation of dandelion root extract: Take dandelion root powder, use 50% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.12 at 60°C, obtain dandelion root extract powder by spray drying, seal for later use.

[0105] 53 Weighing and mixing Accurately weigh according to the formula ratio 300 g of the milk thistle extract prepared above, 450 g of artichoke extract, and 350 g of dandelion root extract. Then accurately weigh according to the excipient formula 820 g of microcrystalline cellulose, 150 g of crospovidone, and 20 g of silicon dioxide, place them in a three-dimensional motion mixer and mix for 30 min until the materials are uniform; finally add 10 g of magnesium stearate, supplement mixing for 5 min to obtain a uniform mixed powder material, sample and test content uniformity, set aside after passing. S4 Formulation forming Use a fully automatic hard capsule filling machine to fill the above mixed powder material into size 0 hard gelatin capsules at a filling weight of 0.4 g per capsule. After polishing, full inspection, inner packaging, and outer packaging, obtain the natural plant liver-protecting hard capsule formulation based on promoting bile secretion.

[0106] Through the scientific combination of milk thistle extract, artichoke extract, and dandelion root extract, this formulation overcomes the limitation of single silymarin which can only target hepatocyte protection and cannot achieve cholagogic and detoxifying effects, achieving the multi-target synergistic liver-protecting action of cholagogic and detoxifying effects + hepatocyte protection + antioxidation. High-dose administration can increase the 4h cumulative bile flow in liver-injured rats by 78.47% compared to the model group, decrease serum alanine aminotransferase ALT by 76.84% compared to the model group, and decrease the content of MDA, the end product of lipid peroxidation in liver tissue, by 62.38% compared to the model group. All core efficacy indicators are significantly superior to commercially available mainstream silymarin liver-protecting preparations, with maximum improvements exceeding 45%. At the same time, all active ingredients are derived from natural plants, and while achieving potent liver-protecting efficacy, they possess better administration safety and

[0107] Embodiment 6

[0108] I. Formulation Formula

[0109] (I) Core Formula of Active Ingredients (in dry parts by weight)

[0110] Milk thistle extract 30 parts, Artichoke extract 45 parts, Dandelion root extract 45 parts. Total parts by weight of active ingredients: 120 parts.

[0111] (II) Excipient Formula The total mass of the formulation in this embodiment is 2200 g, wherein the total mass of active ingredients is 1200 g, the total mass of excipients is 1000 g, and the excipients account for 45.5% of the total mass of the formulation, meeting the usage requirement of 10%-90%. The specific composition of excipients is as follows: microcrystalline cellulose (filler) 820 g, crospovidone (disintegrant) 150 g, silicon dioxide (glidant) 20 g, magnesium stearate (lubricant) 10 g.

[0112] (Ill) Raw Material Quality Control Standards Artichoke extract: mass content of cynarin is 3.2%, meeting the requirement of >2.5%; Milk thistle extract: mass content of silymarin is 83.5%, meeting the requirement of >80%; Dandelion root extract: mass content of total flavonoids is 4.8%, meeting the requirement of >4%.

[0113] II. Formulation Preparation Method

[0114] 51 Raw material pretreatment Respectively take dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after air separation for impurity removal, washing with purified water, drying with hot air at 60 °C to a moisture content of <8%, respectively grind using a universal grinder and pass through a 40-mesh sieve to obtain defatted milk thistle seed meal powder, artichoke leaf powder, and dandelion root powder, seal for later use.

[0115] 52 Extract preparation (1) Preparation of artichoke extract: Take artichoke leaf powder, use 60% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.15 at 60°C, obtain artichoke extract powder by spray drying, seal for later use. (2) Preparation of milk thistle extract: Take defatted milk thistle seed meal powder, use 70% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:10, heat and reflux extract twice, each time for 2 h; combine the two extracts, concentrate under vacuum and reduced pressure until no alcohol odor remains, defat with petroleum ether, purify with macroporous adsorption resin, concentrate the eluate under reduced pressure and then spray dry to obtain milk thistle extract powder, seal for later use. (3) Preparation of dandelion root extract: Take dandelion root powder, use 50% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.12 at 60°C, obtain dandelion root extract powder by spray drying, seal for later use.

[0116] 53 Weighing and mixing Accurately weigh according to the formula ratio 300 g of the milk thistle extract prepared above, 450 g of artichoke extract, and 450 g of dandelion root extract. Then accurately weigh according to the excipient formula 820 g of microcrystalline cellulose, 150 g of crospovidone, and 20 g of silicon dioxide, place them in a three-dimensional motion mixer and mix for 30 min until the materials are uniform; finally add 10 g of magnesium stearate, supplement mixing for 5 min to obtain a uniform mixed powder material, sample and test content uniformity, set aside after passing.

[0117] 54 Formulation forming Use a fully automatic hard capsule filling machine to fill the above mixed powder material into size 0 hard gelatin capsules at a filling weight of 0.4 g per capsule. After polishing, full inspection, inner packaging, and outer packaging, obtain the natural plant liver-protecting hard capsule formulation based on promoting bile secretion.

[0118] Through the scientific combination of milk thistle extract, artichoke extract, and dandelion root extract, this formulation greatly overcomes the limitations of single silymarin which can only target hepatocyte protection and cannot achieving cholagogic and detoxifying effects, achieving the multi-target potent synergistic liver-protecting action of cholagogic and detoxifying effects + hepatocyte protection + antioxidation. High-dose administration can increase the 4h cumulative bile flow in liver-injured rats by 86.11% compared to the model group, decrease serum alanine aminotransferase ALT by 81.26% compared to the model group, and decrease the content of MDA, the end product of lipid peroxidation in liver tissue, by 66.78% compared to the model group. All core efficacy indicators are extremely significantly superior to commercially available mainstream silymarin liver-protecting preparations, with maximum improvements exceeding 52%. At the same time, all active ingredients are derived from natural plants, and while achieving potent liver-protecting efficacy, they possess excellent administration safety and tolerability, adaptable to the intensive liver protection needs of populations with a higher risk of liver injury.

[0119] Comparative Example

[0120] I. Formulation Formula

[0121] (I) Core Formula of Active Ingredients (in dry parts by weight)

[0122] Milk thistle extract 30 parts, Artichoke extract 45 parts, Dandelion root extract 25 parts. Total parts by weight of active ingredients: 100 parts.

[0123] (II) Excipient Formula

[0124] The total mass of the formulation in this embodiment is 2000 g, wherein the total mass of active ingredients is 1000 g, the total mass of excipients is 1000 g, and the excipients account for 50% of the total mass of the formulation, meeting the usage requirement of 10%-90%. The specific composition of excipients is as follows: microcrystalline cellulose (filler) 820 g, crospovidone (disintegrant) 150 g, silicon dioxide (glidant) 20 g, magnesium stearate (lubricant) 10 g.

[0125] (III) Raw Material Quality Control Standards

[0126] Artichoke extract: mass content of cynarin is 3.2%, meeting the requirement of >2.5%;

[0127] Milk thistle extract: mass content of silymarin is 83.5%, meeting the requirement of >80%;

[0128] Dandelion root extract: mass content of total flavonoids is 4.8%, meeting the requirement of >4%.

[0129] IE Formulation Preparation Method 51 Raw material pretreatment

[0130] Respectively take dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after air separation for impurity removal, washing with purified water, drying with hot air at 60 °C to a moisture content of <8%, respectively grind using a universal grinder and pass through a 40-mesh sieve to obtain defatted milk thistle seed meal powder, artichoke leaf powder, and dandelion root powder, seal for later use.

[0131] 52 Extract preparation

[0132] (1) Preparation of artichoke extract: Take artichoke leaf powder, use 60% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.15 at 60°C, obtain artichoke extract powder by spray drying, seal for later use. (2) Preparation of milk thistle extract: Take defatted milk thistle seed meal powder, use 70% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:10, heat and reflux extract twice, each time for 2 h; combine the two extracts, concentrate under vacuum and reduced pressure until no alcohol odor remains, defat with petroleum ether, purify with macroporous adsorption resin, concentrate the eluate under reduced pressure and then spray dry to obtain milk thistle extract powder, seal for later use. (3) Preparation of dandelion root extract: Take dandelion root powder, use 50% ethanol aqueous solution as extraction solvent, add solvent at a solid-liquid ratio of 1:15, heat and reflux extract twice, each time for 1.5 h; combine the two extracts, concentrate under vacuum and reduced pressure to a clear paste with a relative density of 1.12 at 60 °C, obtain dandelion root extract powder by spray drying, seal for later use.

[0133] 53 Weighing and mixing

[0134] Accurately weigh according to the formula ratio 300 g of the milk thistle extract prepared above, 450 g of artichoke extract, and 250 g of dandelion root extract. Then accurately weigh according to the excipient formula 820 g of microcrystalline cellulose, 150 g of crospovidone, and 20 g of silicon dioxide, place them in a three-dimensional motion mixer and mix for 30 min until the materials are uniform; finally add 10 g of magnesium stearate, supplement mixing for 5 min to obtain a uniform mixed powder material, sample and test content uniformity, set aside after passing.

[0135] S4 Formulation forming

[0136] Use a fully automatic hard capsule filling machine to fill the above mixed powder material into size 0 hard gelatin capsules at a filling weight of 0.4 g per capsule. After polishing, full inspection, inner packaging, and outer packaging, obtain the natural plant liver-protecting hard capsule formulation based on promoting bile secretion.

[0137] The specific contents are shown in the following table:

[0138] By fixing the amounts of artichoke extract and dandelion root extract and only adjusting the addition ratio of milk thistle extract, Embodiments 1 to 3 completely verify the efficacy gradient variation pattern of this natural plant liver-protecting formulation. The results show that milk thistle extract, as the core functional component for hepatocyte protection and anti-oxidative damage in the formulation, has a content clearly positively correlated with the overall liver-protecting efficacy of the formulation. Within the addition range of 20-50 parts, as the amount of milk thistle extract increases, the formulation's effects in repairing hepatocyte damage and necrosis, reversing abnormalities in core liver function indicators, inhibiting lipid peroxidation damage in liver tissue, and enhancing the body's endogenous antioxidant defense capacity are all enhanced in a stepwise manner, forming a stronger synergistic effect with the cholagogic and detoxifying effects of artichoke extract and dandelion root extract. The efficacy advantage compared to commercially available mainstream silymarin liver-protecting preparations becomes increasingly significant. All embodiment formulations, through the scientific combination of the three natural plant extracts, achieve the multi-target synergistic liver-protecting action of "cholagogic and detoxifying effects + hepatocyte protection + antioxidation", overcoming the limitations of single silymarin which can only target hepatocyte protection and cannot achieve cholagogic and detoxifying effects. Moreover, all active ingredients are derived from natural plants and possess good administration safety and tolerability at different dosage gradients. By adjusting the amount of milk thistle extract, it can precisely adapt to the differentiated liver protection needs of populations with different levels of liver injury risk and different usage scenarios.

[0139] By fixing the amounts of milk thistle extract and artichoke extract and only adjusting the addition ratio of dandelion root extract, Embodiments 4 to 6 completely verify the efficacy gradient variation pattern of this natural plant liver-protecting formulation. The results show that dandelion root extract, as one of the core components for cholagogic and detoxifying effects, anti-inflammation, and antioxidation in the formulation, has a content clearly positively correlated with the overall liver-protecting efficacy of the formulation. Within the addition range of 15-45 parts, as the amount of dandelion root extract increases, the formulation's effects in promoting bile secretion, accelerating hepatobiliary toxin excretion, protecting hepatocyte integrity, and enhancing the body's antioxidant capacity are all enhanced in a stepwise manner. The efficacy advantage compared to single silymarin preparations becomes increasingly significant. All embodiment formulations, through the scientific combination of the three natural plant extracts, achieve the multi-target synergistic liver-protecting action of "cholagogic and detoxifying effects + hepatocyte protection + antioxidation", breaking through the efficacy limitations of a single liver-protecting component. Moreover, all active ingredients are derived from natural plants and possess good administration safety and tolerability at different dosage gradients. By adjusting the amount of dandelion root extract, it can precisely adapt to the differentiated liver protection needs of different populations.

[0140] The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention in any form. Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art, without departing from the scope of the technical solution of the present invention, can make some changes or modifications to equivalent embodiments with equivalent changes using the above-disclosed technical content. However, any simple modification, equivalent change, and modification made to the above embodiments based on the technical essence of the present invention, without departing from the content of the technical solution of the present invention, still fall within the scope of the technical solution of the present invention.

Claims

CLAIMS1. A natural plant liver-protecting formulation based on promoting bile secretion, characterized in that it is prepared from the following raw materials in parts by weight:The active ingredients of the formulation consist of milk thistle extract, artichoke extract, and dandelion root extract; the formulation achieves the core functions of liver protection and antioxidation through the multi-target synergistic actions of promoting bile secretion, cholagogic and detoxifying effects, and hepatocyte protection.

2. The natural plant liver-protecting formulation based on promoting bile secretion according to claim 1, characterized in that, in terms of dry parts by weight, the amounts of the active ingredients are: 10-60 parts of milk thistle extract, 20-70 parts of artichoke extract, and 10-50 parts of dandelion root extract.

3. The natural plant liver-protecting formulation based on promoting bile secretion according to claim 2, characterized in that, in terms of dry parts by weight, the amounts of the active ingredients are: 20-50 parts of milk thistle extract, 30-60 parts of artichoke extract, and 20-40 parts of dandelion root extract.

4. The natural plant liver-protecting formulation based on promoting bile secretion according to claim 3, characterized in that, in terms of dry parts by weight, the active ingredients consist of 30 parts of milk thistle extract, 45 parts of artichoke extract, and 25 parts of dandelion root extract.

5. The natural plant liver-protecting formulation based on promoting bile secretion according to claim 1, characterized in that the mass content of cynarin in the artichoke extract is >2.5%; the mass content of silymarin in the milk thistle extract is >80%; the mass content of total flavonoids in the dandelion root extract is >4%.

6. The natural plant liver-protecting formulation based on promoting bile secretion according to claim 1, characterized in that the formulation further comprises pharmaceutically or health food acceptable excipients, the mass of the excipients accounting for 10%-90% of the total mass of the formulation.

7. The natural plant liver-protecting formulation based on promoting bile secretion according to claim 6, characterized in that the excipients are selected from one or more of fillers, disintegrants, lubricants, binders, and glidants; the dosage form of the formulation is an oral preparation, specifically any one of tablets, hard capsules, granules, powders, and pills.

8. A preparation of a natural plant liver-protecting formulation based on promoting bile secretion, for preparing the natural plant liver-protecting formulation based on promoting bile secretion according to any one of claims 1-7, characterized in that it comprises the following steps:

51. Raw material pretreatment: respectively taking dried defatted milk thistle seed meal, artichoke leaves, and dandelion roots, after impurity removal, cleaning, drying, and grinding, respectively obtaining powders of each raw material;52. Extract preparation: respectively subjecting each raw material powder to extraction, solid-liquid separation, concentration, and drying to obtain milk thistle extract, artichoke extract, and dandelion root extract;53. Weighing and mixing: weighing each extract according to the formula ratio, adding optional excipients, and placing in mixing equipment for thorough mixing to obtain a mixed powder material;54. Formulation forming: preparing the mixed powder material into the corresponding dosage form to obtain the natural plant liver-protecting formulation.

9. The preparation of the natural plant liver-protecting formulation based on promoting bile secretion according to claim 8, characterized in that the preparation process for each extract in step S2 is specifically as follows:Preparation of the artichoke extract: using artichoke leaf powder as raw material, using 50%-70% ethanol aqueous solution as extraction solvent, solid-liquid ratio 1:10-1 :20, reflux extraction 2-3 times, each time for 1-2 h, combining the extracts, concentrating under reduced pressure to a clear paste with a relative density of 1.10-1.20 at 60°C, and obtaining by spray drying; Preparation of the milk thistle extract: using defatted milk thistle seed meal powder as raw material, using 60%-80% ethanol aqueous solution as extraction solvent, solid-liquid ratio 1:8-1: 15, reflux extraction 2-3 times, each time for 1.5-2.5 h, combining the extracts, and obtaining by concentration under reduced pressure, defatting, purification, and spray drying; Preparation of the dandelion root extract: using dandelion root powder as raw material, using 40%-60% ethanol aqueous solution as extraction solvent, solid-liquid ratio 1:10-1 :20, reflux extraction 2-3 times, each time for 1-2 h, combining the extracts, concentrating under reduced pressure to a clear paste with a relative density of 1.10-1.15 at 60°C, and obtaining by spray drying.

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