A plant extract composition for relieving liver qi stagnation and nodules

Abstract

The present application relates to the technical field of traditional Chinese medicine preparation, and discloses a plant extract composition for relieving liver-QI stagnation and nodules, which is made of isomaltooligosaccharide, matrix precursor liquid derived from kelp and licorice, lipophilic concentrate, natural organic acid adjusting liquid and heat-sensitive active liquid. By in-situ reaction of the matrix precursor liquid and the organic acid, an interpenetrating network structure of glycyrrhizic acid and alginic acid is constructed in the system, and an oil-in-water emulsion gel with thixotropy and pH responsiveness is formed. The preparation method comprises matrix emulsification, organic acid atomization instantaneous initiation, low-temperature composite heat-sensitive component and double-stage cooling shaping. The present application realizes targeted enteric release of the drug by the interpenetrating network, and protects the heat-sensitive component, thus solving the problems of poor stability and low bioavailability of traditional preparations, and having the effects of soothing the liver and regulating Qi, softening and resolving nodules, and strengthening the body resistance.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, and in particular to a plant extract composition for relieving liver qi stagnation and nodules. Background Technology

[0002] The fast pace of modern life and increased mental stress have led to a year-on-year rise in the incidence of liver qi stagnation and its secondary complications. In traditional Chinese medicine theory, long-term liver qi stagnation can cause obstruction of body fluid distribution, leading to the accumulation of dampness and phlegm. The obstruction of qi and phlegm further hinders blood circulation, ultimately resulting in nodules in areas such as the thyroid, breast, or lungs. Clinical treatment for these conditions often employs compound Chinese herbal formulas that soothe the liver, regulate qi, resolve phlegm and nodules, and promote blood circulation. Current administration methods primarily focus on conventional dosage forms such as traditional decoctions, pastes, oral liquids, or granules.

[0003] However, the aforementioned traditional dosage forms have certain technical limitations in terms of preparation processes and drug delivery mechanisms. Most existing liquid formulations rely mainly on simple physical mixing or thermal concentration processes, without constructing stable microscopic carrier systems. Because traditional Chinese medicine extracts are complex in composition, containing large amounts of polysaccharides, proteins, tannins, and small molecule glycosides, these components are highly susceptible to physicochemical interactions in liquid environments, leading to flocculation, precipitation, or stratification during storage. This not only affects product homogeneity but may also cause degradation of the active ingredients.

[0004] More importantly, many active ingredients with the effect of softening and dispersing nodules (such as certain saponins, bioactive enzymes, or volatile oils) are quite sensitive to environmental pH and temperature. Traditional preparations, after oral administration, are directly exposed to the highly acidic gastric juice environment, making them prone to hydrolysis or denaturation and inactivation, failing to effectively reach the small intestine for absorption, resulting in a significant reduction in drug bioavailability. Furthermore, to achieve effective therapeutic concentrations, traditional paste-like preparations often have excessive viscosity and lack good rheological properties, resulting in a sticky texture, severe adhesion to the digestive tract walls, and difficulty in effective spreading and retention on the digestive tract mucosa. Therefore, developing a novel carrier system that can maintain the physical stability of traditional Chinese medicine compound preparations while achieving gastric protection and targeted intestinal release of active ingredients has become a pressing technical challenge in the field of traditional Chinese medicine preparations. Summary of the Invention

[0005] The technical problem solved by this invention is that existing traditional Chinese medicine preparations for treating or relieving liver qi stagnation and nodules usually adopt traditional decoction or simple physical mixing processes, which have technical defects such as poor stability of active ingredients, easy precipitation or layering, poor taste, and low bioavailability due to premature release of drugs in the stomach.

[0006] To address the above problems, the present invention provides the following technical solution:

[0007] In a first aspect, the present invention provides a plant extract composition for relieving liver qi stagnation and nodules. The composition has shear-thinning thixotropic properties and pH-responsive release characteristics, and is made from raw materials comprising the following parts by weight: 45 to 60 parts of isomaltooligosaccharide; 20 to 30 parts of matrix precursor liquid derived from kelp and licorice; 5 to 10 parts of lipophilic concentrate derived from peach kernel and dried ginger; 8 to 15 parts of natural organic acid regulating liquid derived from tangerine peel and citron; and 4 to 8 parts of thermosensitive active liquid derived from dandelion and ginseng. The composition contains an interpenetrating network structure of glycyrrhizic acid and alginic acid formed through the in-situ reaction of the matrix precursor liquid and the natural organic acid regulating liquid.

[0008] By adopting the above technical solution, this invention does not employ conventional methods of thickening with added gelling agents, but instead utilizes the inherent chemical properties of the raw materials to construct a self-assembling carrier system. When the natural organic acid conditioning liquid is introduced into the system, the hydrogen ions it provides (H+) + This disrupts the original solubility equilibrium of alginate and glycyrrhizate in the matrix precursor solution, initiating a phase transition process at the microscopic level. Specifically, the carboxylate ions in sodium alginate combine with hydrogen ions, displacing sodium ions. This leads to enhanced hydrogen bonding between polymer chain segments and aggregation, forming a water-insoluble alginate gel framework. The reaction process is shown in the following equation:

[0009] R-COO - Na + +H + →R-COOH↓+Na + ;

[0010] In the formula, R represents the alginate polymer chain segment.

[0011] Meanwhile, glycyrrhizic acid molecules, with their amphiphilic structure, exhibit reduced solubility in acidic environments. Hydrophobic interactions promote their directional alignment and self-assembly into micelles or fibrous structures. These secondary structures interweave and entangle within the gaps in the gel framework formed by alginate. Although no chemical cross-linking occurs, they form a physically entangled interpenetrating network (IPN) in space. This dual-network structure not only significantly enhances the physical stability of the system and effectively prevents stratification and precipitation during storage, but more importantly, it endows the composition with intelligent responsiveness to the pH environment of the digestive tract.

[0012] Because this network structure is mainly maintained by carboxyl groups, in the acidic environment of the stomach at pH 1.2, the carboxyl groups remain protonated, and the network structure contracts densely, which can block the penetration of gastric juice and the diffusion of internal active ingredients, thereby protecting heat-sensitive and lipophilic components from gastric acid damage. Once it enters the intestinal environment at pH 6.8, the carboxyl groups rapidly undergo deprotonation and dissociation into carboxylate anions (-COO-). -The electrostatic repulsion between the chain segments causes the gel network to swell and disintegrate, enabling enteric-coated, site-specific release of the drug. Furthermore, this physical network based on weak interactions endows the fluid with significant thixotropy; that is, its viscosity decreases under swallowing shear forces to facilitate administration, and its structure rapidly recovers after standing to facilitate spreading on mucosal surfaces.

[0013] Preferably, the matrix precursor liquid is a liquid with a relative density of 1.12 to 1.15 prepared by water extraction, centrifugation and concentration of the following raw materials in parts by weight: 15 to 20 parts kelp, 12 to 15 parts licorice, 10 to 12 parts poria cocos and 5 to 6 parts donkey-hide gelatin.

[0014] By employing the above technical solution, kelp and licorice serve as core materials for constructing the framework, providing sources of alginic acid and glycyrrhizic acid, respectively. The introduction of Poria cocos polysaccharides increases the viscoelasticity of the system, while the collagen peptide chains provided by donkey-hide gelatin contain abundant amino groups, which can form polyelectrolyte complexes with the carboxyl groups of alginic acid under specific pH conditions. This synergistic effect of multiple components further enhances the mechanical strength of the gel network. Controlling the relative density between 1.12 and 1.15 is to maintain suitable fluidity while ensuring a high molecular weight for subsequent processing.

[0015] Preferably, the lipophilic concentrate is an oily substance prepared by heating and reflux extraction of the following raw materials in parts by weight with 95% ethanol: 8 parts peach kernel, 5 parts dried ginger, 6 parts angelica, 5 parts Lindera leaf, 5 parts Angelica dahurica, and 1 part saffron.

[0016] By employing the above-mentioned technical solution, high-concentration ethanol can efficiently enrich lipophilic components such as fatty oil in peach kernels, gingerol in dried ginger, and volatile oils in angelica and angelica dahurica. During the composition construction process, these components are encapsulated as dispersed phases within the aforementioned interpenetrating network. This physical isolation effectively reduces the risk of oxidation upon contact with oxygen and minimizes the loss of volatile components.

[0017] Preferably, the natural organic acid regulating liquid is a liquid with a pH of 3.1 prepared by extracting and concentrating the following raw materials in parts by weight with 60% ethanol: 8 parts dried tangerine peel, 8 parts citron, and 12 parts mulberry; the thermosensitive active liquid is a liquid prepared by extracting and concentrating the following raw materials in parts by weight with warm soaking: 8 parts dandelion, 4 parts ginseng, 6 parts platycodon, 8 parts polygonatum, 8 parts ophiopogon, 4 parts ganoderma, and 1 part snow lotus culture.

[0018] By adopting the above technical solutions, tangerine peel, citron, and mulberry not only exert their qi-regulating effects as medicinal components, but their extracts are also rich in complex natural organic acids such as citric acid and malic acid (pH 3.1), which are precisely within the critical pH range for inducing the phase transition between alginic acid and glycyrrhizic acid, thus realizing the design concept of "drug and adjuvant integration". For raw materials containing bioactive enzymes and heat-labile glycosides, warm maceration extraction is used, with the extract added at the end of the process to maximize the preservation of their bioactivity.

[0019] Preferably, the composition is an oil-in-water emulsion gel, wherein the lipophilic concentrate serves as the dispersed phase and is dispersed in droplet form in a continuous phase gel network composed of the isomaltooligosaccharide, matrix precursor liquid, natural organic acid conditioning liquid, and thermosensitive active liquid.

[0020] By employing the above technical solution, the system utilizes glycyrrhizic acid and naturally occurring protein-polysaccharide complexes in the matrix as surfactants to disperse the lipophilic concentrate into fine droplets. The high-viscosity continuous phase gel network restricts the Brownian motion of the oil droplets, kinetically hindering their aggregation and coalescence. This structure allows the system to achieve long-term stability without the addition of synthetic surfactants, while isomaltooligosaccharide, as the main medium of the continuous phase, provides a suitable osmotic pressure environment while regulating water activity.

[0021] At the pharmacodynamic level, this invention addresses the pathological evolution chain of liver qi stagnation leading to impaired fluid distribution, which in turn results in phlegm accumulation, blood stasis obstructing the collaterals, and ultimately nodules. It constructs a four-dimensional synergistic system of "soothing the liver and regulating qi, softening and dispersing nodules, promoting blood circulation and removing blood stasis, and strengthening the body's resistance." The tangerine peel, citron, and Lindera leaf in the formula enter the liver and spleen meridians, regulating the ascending and descending of qi to clear liver qi stagnation and block the generation of pathological products at the source. Kelp, as a core component for softening and dispersing nodules, has a salty and cold nature that can eliminate phlegm and soften nodules, working in conjunction with Poria to strengthen the spleen and eliminate dampness, thus eliminating the source of phlegm production. Peach kernel, saffron, and Angelica sinensis enter the blood level, intervening in the blood stasis state formed by prolonged illness, improving microcirculation, and promoting the metabolism and absorption of pathological products.

[0022] In addition, considering that the course of nodular disease is often accompanied by stagnation of internal heat and deficiency of vital energy, dandelion is introduced into the formula to clear heat and detoxify, targeting the local inflammatory reaction caused by prolonged stagnation turning into internal heat; ginseng, Ganoderma lucidum, donkey-hide gelatin and Solomon's seal play the role of tonifying qi and nourishing yin, and strengthening the body's resistance. This can not only enhance the body's immune surveillance function to clear abnormal tissue, but also prevent aggressive ingredients from damaging vital energy. The whole formula uses both cold and hot herbs, and combines attack and tonification, to achieve both symptomatic and root-cause treatment of liver stagnation nodular lesions.

[0023] Secondly, the present invention provides a method for preparing a plant extract composition for relieving liver qi stagnation and nodules, comprising the following steps:

[0024] Step 1, matrix mixing and emulsification: Mix isomaltooligosaccharide, matrix precursor liquid and lipophilic concentrate, and shear emulsify at a temperature of 75°C to 80°C to form an emulsified matrix system.

[0025] Step 2, instantaneous acidification initiation: Maintain the temperature at 75°C to 80°C, atomize the natural organic acid conditioning liquid into the emulsion matrix system, and continue shearing under turbulent conditions to construct a primary gel network;

[0026] Step 3, thermosensitive component composite: lower the system temperature to 68℃ to 72℃, add thermosensitive active liquid, and stir at low speed to mix evenly;

[0027] Step 4, two-stage cooling and shaping: The material obtained in step 3 is subjected to programmed cooling. First, a rapid cooling stage is performed to fix the gel skeleton, and then a slow cooling stage is performed to room temperature to obtain the final product.

[0028] By adopting the above technical solution, this invention employs a combined process of "thermal emulsification-in-situ acid-induced gelation-staged cooling" to solve the process problems of uneven gelation and easy deactivation of active ingredients in high-viscosity systems. Specifically, in step 2, by spraying natural organic acid in the form of atomization into the matrix in a high-shear turbulent state, the contact area between the acid and the matrix is ​​significantly increased, allowing hydrogen ions to achieve uniform distribution at the microscale before initiating the gelation reaction. This process control strategy effectively solves the problems of local over-gelation (agglomeration) and overall network inhomogeneity caused by the acid diffusion rate being lower than the gelation reaction rate in traditional acidification processes, thereby constructing a uniform and fine-textured interpenetrating network.

[0029] In addition, the addition of the thermosensitive active liquid is delayed until the cooling stage after the formation of the primary gel network (step 3). On the one hand, the already formed semi-solid network restricts the thermal movement of the active ingredients, and on the other hand, the high-temperature shearing process is avoided, thus maximizing the preservation of the activity of biological enzymes and thermosensitive glycosides.

[0030] Preferably, the specific parameters for the two-stage cooling and shaping in step 4 are as follows: in the first stage, the material temperature is reduced from 68°C to 72°C to 42°C to 48°C at a rate of 2°C to 6°C per minute; in the second stage, the material temperature is reduced from 42°C to 48°C to 20°C to 25°C at a rate of 0.5°C to 1.5°C per minute.

[0031] By adopting the above technical solution, the cooling strategy is designed based on the relaxation theory in polymer physics: the rapid cooling in the first stage allows the system to quickly pass through the sol-gel transition point, kinetically "freezing" the spatial position of the dispersed phase droplets and preventing them from coalescing or floating during the cooling process; the slow cooling in the second stage provides sufficient relaxation time for the polymer chain segments, enabling them to rearrange and repair hydrogen bonds at lower energy levels, eliminating the internal stress caused by rapid cooling, effectively avoiding dehydration shrinkage or cracking of the finished product during storage, and ensuring the long-term physical stability of the product.

[0032] Preferably, the atomization injection in step 2 is carried out by a pressure atomizing tank and an atomizing nozzle, and the acid flow rate is controlled at 0.8 to 1.5 kg per minute.

[0033] By employing the above technical solution, liquid organic acids are converted into micron-sized acid mist droplets using pressure atomization. Combined with specific flow rate control, this achieves the desired effect for the reaction initiator (H... + The precise spatiotemporal release of the alginate and glycyrrhizic acid is achieved. A suitable flow rate ensures the continuous progress of the acidification reaction while preventing disruption of the self-assembly pathways of alginate and glycyrrhizic acid due to sudden spikes in local acid concentration, thus ensuring the integrity of the interpenetrating network structure.

[0034] Preferably, the matrix precursor solution used in step 1 is prepared by the following method: take kelp, licorice, poria cocos and donkey-hide gelatin, crush them, add purified water, and add an alkaline regulator to adjust the pH value to 8.2-8.5; heat to extract, filter, centrifuge the filtrate at a speed of 10000 rpm to 12000 rpm to remove insoluble matter; concentrate the supernatant under reduced pressure to obtain the product.

[0035] By adopting the above technical solution, the weakly alkaline extraction environment (pH 8.2-8.5) can promote the conversion of insoluble alginic acid in kelp into water-soluble sodium alginate, while increasing the dissolution rate of glycyrrhizic acid; the ultra-high speed centrifugation process completely removes fine fibers and insoluble particles from the extract, eliminates potential gel defects, and thus significantly improves the light transmittance and smoothness of the final product.

[0036] Preferably, in step 1, the speed of the high-shear emulsifier is set to 3500 rpm to 5500 rpm, and the constant temperature shearing time is 10 to 20 minutes.

[0037] By adopting the above technical solution, the shear parameter provides suitable hydrodynamic energy, which is sufficient to overcome the tension of the oil-water interface and disperse the lipophilic concentrate to micron-sized particles. At the same time, controlling the shear time to within 20 minutes avoids the mechanical degradation of polymer chains caused by prolonged high shear, ensuring that the matrix precursor liquid has sufficient molecular weight to form a robust skeleton during the subsequent gelation process.

[0038] Thirdly, this invention provides the use of plant extract compositions that relieve liver qi stagnation and nodules in the preparation of food or health food. With its unique interpenetrating network structure and thixotropic properties, it can be consumed directly as an emulsified gel or widely used as a core active matrix in the preparation of various foods or health food.

[0039] In practical applications, the food or health food can be freeze-dried into a solid form or its rheological properties can be adjusted by adding appropriate excipients to produce various product forms as required. The dosage forms of the food or health food include, but are not limited to, pastes, pills, powders, granules, tablets, capsules, oral liquids, beverages, emulsions or gels.

[0040] In summary, the present invention has at least one of the following beneficial technical effects:

[0041] 1. This invention utilizes the in-situ self-assembly of glycyrrhizic acid and alginic acid to form an interpenetrating network structure, stably encapsulating lipophilic components within a gel skeleton, effectively solving the problems of precipitation, stratification, and oxidative deterioration that easily occur during the storage of traditional Chinese medicine liquid preparations; at the same time, the unique shear-thinning thixotropy of this system significantly improves the swallowing taste and compliance of the product.

[0042] 2. The composition of this invention exhibits significant pH-responsive characteristics, contracting and densifying in the acidic environment of the stomach to protect the heat-sensitive and lipophilic active ingredients, and rapidly swelling and disintegrating in the intestinal fluid environment to release the drug. This mechanism avoids drug irritation to the gastric mucosa and significantly improves the intestinal absorption rate and bioavailability of the active ingredients.

[0043] 3. The formulation of this invention closely follows the pathological chain of "qi stagnation-phlegm coagulation-blood stasis". Through the synergistic effect of soothing the liver and regulating qi, softening and dispersing nodules, promoting blood circulation and removing blood stasis, and strengthening the body's resistance, it can not only relieve the symptoms of nodules caused by liver qi stagnation, but also regulate the body's immune function, fundamentally improve the constitution, and prevent nodule recurrence.

[0044] 4. The preparation method of this invention adopts instantaneous atomization acidification initiation and two-stage cooling and shaping technology, which overcomes the process bottlenecks of uneven gelation and easy deactivation of heat-sensitive components in high viscosity systems. The resulting product has a fine and uniform texture, good batch-to-batch stability, and is suitable for large-scale industrial production. Attached Figure Description

[0045] Figure 1 The following is a comparison of the rheological properties of Example 1 and Comparative Example 4 of the present invention; wherein, (a) is a comparison of the apparent viscosity changes of the two samples at different shear rates; and (b) is a comparison of the viscosity-time curves in the three-stage thixotropic (3ITT) test.

[0046] Figure 2The figures show a comparison of the moisture state characterization of Example 1 and Comparative Example 3 of the present invention; wherein, (a) is the transverse relaxation time distribution curve obtained based on LF-NMR testing; and (b) is the heat flow curve during the DSC heating scan process. Detailed Implementation

[0047] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are merely some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0048] The main raw materials and reagents used in the following examples and comparative examples have the following sources and specifications. Reagents not specifically mentioned are all commercially available analytical grade or higher grade products.

[0049] Isomaltooligosaccharide, CAS No.: 499-40-1 (calculated as isomaltose), is a colorless to pale yellow viscous liquid. Its main components include isomaltose, panose, isomalttriose and oligosaccharides with more than four sugars. The solid content is 75%, the glucose equivalent (DE value) is ≤20, and the pH value is 4.0 to 6.0.

[0050] The plant raw materials involved in this invention, including kelp, licorice, poria cocos, donkey-hide gelatin, peach kernel, dried ginger, angelica sinensis, lindera leaf, angelica dahurica, saffron, tangerine peel, citron, mulberry, dandelion, ginseng, platycodon grandiflorus, polygonatum odoratum, ophiopogon japonicus, ganoderma lucidum (red ganoderma), and snow lotus culture, are all commercially available medicinal or food-grade raw materials, and comply with the standards of Part I of the 2020 edition of the Pharmacopoeia of the People's Republic of China or the relevant food safety standards approved by the National Health Commission.

[0051] Preparation Example 1:

[0052] This preparation example provides a method for preparing a matrix precursor fluid, including the following steps:

[0053] Weigh 15 kg of kelp, 12 kg of licorice, 10 kg of poria cocos, and 5 kg of donkey-hide gelatin, and grind them into coarse powder. Add purified water in an amount equal to 12 times the total weight of the raw materials, and add an appropriate amount of sodium carbonate to adjust the pH of the extraction solvent to 8.2. Heat to 100℃ and maintain a gentle boiling state for extraction twice, each time for 2 hours. Combine the extracts, filter through a 200-mesh filter to remove the residue, and centrifuge the filtrate at 12,000 rpm to remove fine insoluble matter. Concentrate the supernatant after centrifugation under reduced pressure at a vacuum of -0.08 MPa and a temperature of 60℃. The relative density was measured to be 1.12 at 60℃, and the matrix precursor solution was obtained for later use.

[0054] Preparation Example 2:

[0055] This preparation example provides a method for preparing a matrix precursor fluid, including the following steps:

[0056] Weigh 20 kg of kelp, 15 kg of licorice, 12 kg of poria cocos, and 6 kg of donkey-hide gelatin, and grind them into coarse powder. Add 15 times the total weight of the raw materials of purified water, and add an appropriate amount of sodium bicarbonate to adjust the pH of the extraction solvent to 8.5. Heat to 95℃ and extract twice, 1.5 hours each time. Combine the extracts and filter through a 200-mesh filter. Centrifuge the filtrate at 10,000 rpm using a tubular centrifuge. Concentrate the supernatant after centrifugation under reduced pressure at a vacuum of -0.08 MPa and a temperature of 65℃. The relative density was measured to be 1.15 at 60℃, and the matrix precursor solution was obtained for later use.

[0057] Preparation Example 3:

[0058] This preparation example provides a method for preparing a lipophilic concentrate, including the following steps:

[0059] Weigh 8 kg of peach kernels, 5 kg of dried ginger, 6 kg of angelica, 5 kg of Lindera leaves, 5 kg of Angelica dahurica, and 1 kg of saffron, and grind them into coarse powder; add 8 times the total weight of the raw materials in 95% (v / v) ethanol; heat and reflux to extract twice, 1.5 hours each time; combine the ethanol extracts and reduce the pressure at 50℃ and -0.08MPa to recover the ethanol until there is no alcohol taste, and obtain an oily lipophilic concentrate for later use.

[0060] Preparation Example 4:

[0061] This preparation example provides a method for preparing a natural organic acid conditioning solution, including the following steps:

[0062] Weigh out 8 kg of dried tangerine peel, 8 kg of citron, and 12 kg of mulberry, and crush them. Add 10 times the total weight of the raw materials in 60% (v / v) ethanol. Heat and reflux twice, 1 hour each time. Combine the extracts, recover the ethanol, and continue to concentrate under reduced pressure at 60℃ and -0.08 MPa until the relative density is measured to be 1.22 at 25℃. The pH value of the concentrate is measured to be 3.1, and the natural organic acid adjusting solution is prepared for use.

[0063] Preparation Example 5:

[0064] This preparation example provides a method for preparing a thermosensitive active liquid, including the following steps:

[0065] Weigh out 8 kg of dandelion, 4 kg of ginseng, 6 kg of platycodon, 8 kg of polygonatum, 8 kg of ophiopogon japonicus, 4 kg of ganoderma lucidum, and 1 kg of snow lotus culture, and crush them. Add purified water in an amount equal to 12 times the total weight of the raw materials. Extract twice at a constant temperature of 65℃ for 2 hours each time. Combine the extracts, filter, and concentrate under reduced pressure at 55℃ and -0.08 MPa until the relative density is measured to be 1.10 at 25℃. The resulting thermosensitive active liquid is ready for use.

[0066] Example 1:

[0067] This embodiment provides a method for preparing a plant extract composition that relieves liver qi stagnation and nodules, including the following steps:

[0068] (1) Matrix mixing and emulsification: In a jacketed temperature-controlled reactor, add 55 kg of isomaltooligosaccharide, 25 kg of matrix precursor liquid obtained in Preparation Example 1 and 5 kg of lipophilic concentrate obtained in Preparation Example 3; turn on the agitator and stir at 60 rpm, and at the same time turn on the high-shear emulsifier and set the speed to 4500 rpm; heat the material to 78°C by jacket heating, and perform constant temperature shear emulsification for 15 minutes to form a uniform emulsion system using the natural surface active ingredients in the matrix.

[0069] (2) Instantaneous acidification initiation: Keep the temperature at 78°C and maintain the high shear emulsifier speed at 4500 rpm. Put 10 kg of the natural organic acid conditioning liquid obtained in Preparation Example 4 into a pressure atomizing tank. Spray the acid liquid into the emulsion matrix system in a mist form through the atomizing nozzle at the top of the reactor at a flow rate of 1.0 kg / min. Use the acid-base reaction to initiate the phase transformation of sodium alginate to alginic acid. After the spraying is completed, continue shearing for 3 minutes to construct the primary gel network.

[0070] (3) Combining of thermosensitive components: Reduce the system temperature to 70°C, add 5 kg of the thermosensitive active liquid obtained in Preparation Example 5, stir at low speed to mix evenly, and stir for 2 minutes to avoid thermal deactivation of active components.

[0071] (4) Two-stage cooling and shaping: Start the program cooling system. In the first stage, the material temperature is rapidly reduced from 70°C to 45°C at a rate of 4°C / min to fix the gel skeleton. In the second stage, the material temperature is slowly reduced from 45°C to 25°C at a rate of 1°C / min to relax and rearrange the molecular chains. Discharge and fill to obtain the finished product.

[0072] Example 2:

[0073] This embodiment provides a method for preparing a plant extract composition that relieves liver qi stagnation and nodules, including the following steps:

[0074] (1) Matrix mixing and emulsification: In a jacketed temperature-controlled reactor, add 45 kg of isomaltooligosaccharide, 30 kg of matrix precursor liquid obtained in Preparation Example 2 and 5 kg of lipophilic concentrate obtained in Preparation Example 3; turn on the agitator and stir at 50 rpm, and at the same time turn on the high-shear emulsifier and set the speed to 3500 rpm; heat the material to 75°C by jacket heating, and perform constant temperature shear emulsification for 20 minutes to form a uniform emulsion matrix system.

[0075] (2) Instantaneous acidification initiation: Keep the temperature at 75°C and maintain the high shear emulsifier speed at 3500 rpm. Put 12 kg of the natural organic acid conditioning liquid obtained in Preparation Example 4 into a pressure atomizing tank. Spray the acid liquid into the emulsion matrix system in a mist form through the atomizing nozzle at the top of the reactor at a flow rate of 0.8 kg / min. Keep the system in a turbulent state during the spraying process. Continue shearing for 5 minutes after the spraying is completed.

[0076] (3) Combining of thermosensitive components: The system temperature was lowered to 68°C, and 8 kg of the thermosensitive active liquid obtained in Preparation Example 5 was added. The mixture was stirred at low speed for 3 minutes to achieve uniform mixing.

[0077] (4) Two-stage cooling and shaping: Start the program cooling system. In the first stage, the material temperature is rapidly reduced from 68℃ to 42℃ at a rate of 2℃ / min. In the second stage, the material temperature is slowly reduced from 42℃ to 20℃ at a rate of 0.5℃ / min. Discharge, fill, and the finished product is obtained.

[0078] Example 3:

[0079] This embodiment provides a method for preparing a plant extract composition that relieves liver qi stagnation and nodules, including the following steps:

[0080] (1) Matrix mixing and emulsification: In a jacketed temperature-controlled reactor, add 60 kg of isomaltooligosaccharide, 20 kg of matrix precursor liquid obtained in Preparation Example 1 and 8 kg of lipophilic concentrate obtained in Preparation Example 3; turn on the agitator and stir at 80 rpm, and at the same time turn on the high-shear emulsifier and set the speed to 5500 rpm; heat the material to 80°C by jacket heating, and perform constant temperature shear emulsification for 10 minutes to form a uniform emulsified matrix system.

[0081] (2) Instantaneous acidification initiation: Keep the temperature at 80℃ and maintain the high shear emulsifier speed at 5500rpm. Put 8kg of the natural organic acid conditioning liquid obtained in Preparation Example 4 into the pressure atomizing tank, and spray the acid liquid into the emulsion matrix system in a mist form through the atomizing nozzle at the top of the reactor at a flow rate of 1.5kg / min. Keep the system in a turbulent state during the spraying process, and continue shearing for 2 minutes after the spraying is completed.

[0082] (3) Combining of thermosensitive components: The system temperature was lowered to 72°C, and 4 kg of the thermosensitive active liquid obtained in Preparation Example 5 was added. The mixture was stirred at low speed for 1 minute.

[0083] (4) Two-stage cooling and shaping: Start the program cooling system. In the first stage, the material temperature is rapidly reduced from 72°C to 48°C at a rate of 6°C / min. In the second stage, the material temperature is slowly reduced from 48°C to 25°C at a rate of 1.5°C / min. Discharge, fill, and the finished product is obtained.

[0084] Example 4:

[0085] This embodiment provides a method for preparing a plant extract composition that relieves liver qi stagnation and nodules, including the following steps:

[0086] (1) Matrix mixing and emulsification: In a jacketed temperature-controlled reactor, add 50 kg of isomaltooligosaccharide, 20 kg of matrix precursor liquid obtained in Preparation Example 1 and 10 kg of lipophilic concentrate obtained in Preparation Example 3; turn on the agitator and stir at 70 rpm, and at the same time turn on the high-shear emulsifier and set the speed to 5000 rpm; heat the material to 78°C by jacket heating, and perform constant temperature shear emulsification for 18 minutes to form a high internal phase emulsion matrix system.

[0087] (2) Instantaneous acidification initiation: Keep the temperature at 78°C and maintain the high shear emulsifier speed at 5000 rpm. Put 15 kg of the natural organic acid conditioning liquid obtained in Preparation Example 4 into a pressure atomizing tank. Spray the acid liquid into the emulsion matrix system in a mist form through the atomizing nozzle at the top of the reactor at a flow rate of 1.2 kg / min. Keep the system in a turbulent state during the spraying process. After the spraying is completed, continue shearing for 3 minutes.

[0088] (3) Combining of thermosensitive components: The system temperature was lowered to 70°C, and 5 kg of the thermosensitive active liquid obtained in Preparation Example 5 was added. The mixture was stirred at low speed for 2 minutes.

[0089] (4) Two-stage cooling and shaping: Start the program cooling system. In the first stage, the material temperature is rapidly reduced from 70℃ to 45℃ at a rate of 5℃ / min. In the second stage, the material temperature is slowly reduced from 45℃ to 22℃ at a rate of 1.0℃ / min. Discharge, fill, and the finished product is obtained.

[0090] Example 5:

[0091] This embodiment provides a method for preparing a solid dosage form of a plant extract composition for relieving liver qi stagnation and nodules, including the following steps:

[0092] (1) Preparation of gel dry powder: Take the plant extract composition (emulsified gel) obtained in Example 1 above, spread it evenly in a freeze drying tray, place it in a vacuum freeze dryer, pre-freeze it at -40℃ for 4 hours, then sublimate it under a vacuum of 5Pa for 24 hours, pulverize it and pass it through an 80-mesh sieve to obtain gel dry powder that retains the micro-network structure.

[0093] (2) Preparation of powder and granules: The gel powder obtained in step (1) is directly packaged into aluminum foil strip bags to obtain powder; if an appropriate amount of dextrin is added and mixed evenly, purified water is added to make soft material and sieve to granulate, and then dried and granulated, granules are obtained.

[0094] (3) Preparation of capsules: Add 0.5% silica as a flow aid to the gel powder obtained in step (1), mix evenly and send it into a fully automatic capsule filling machine to fill empty capsules, control the filling difference, polish and seal to obtain capsules.

[0095] (4) Tablet preparation: Take the gel powder obtained in step (1), add an appropriate amount of microcrystalline cellulose and magnesium stearate, mix evenly, and then compress it into tablets using a rotary tablet press to obtain tablets.

[0096] Example 6:

[0097] This embodiment provides a method for preparing liquid and semi-solid dosage forms of plant extract compositions for relieving liver qi stagnation and nodules, including the following steps:

[0098] (1) Preparation of oral liquid and beverage: Taking advantage of the shear thinning thixotropic properties of the composition, the plant extract composition prepared in Example 1 was added to 5 to 10 times its weight of purified water, and the network was moderately depolymerized and uniformly dispersed under high-speed shear (3000 rpm); an appropriate amount of fruit juice and sweetener were added for preparation, and after filtration and aseptic filling, a fluidized oral liquid or beverage was obtained.

[0099] (2) Preparation of paste and gel: The material obtained from step (4) of Example 1 is itself a stable gel, which can be directly and sterilely packaged; if it is slowly stirred and mixed with 15% of refined honey at 50°C, and then concentrated slightly and packaged while hot, and cooled, a paste product with a mellow texture can be made.

[0100] Example 7:

[0101] This embodiment provides a method for preparing other dosage forms of plant extract compositions that relieve liver qi stagnation and nodules, including the following steps:

[0102] (1) Preparation of pills: The gel powder obtained by freeze drying in step (1) of Example 5 is mixed with honey that has been heated and cooled to 60°C at a weight ratio of 1:1.2. The mixture is placed in a medicine mixing machine and mixed evenly to form a soft and hard pill. Then it is placed in a pill making machine and rolled into a large honey pill. The pill is wrapped with wax paper and sealed with a plastic shell.

[0103] (2) Preparation of emulsion: Take the high internal phase emulsion matrix system (i.e., plant extract composition) obtained in Example 1, add 2% of the total weight of Tween-80 and an appropriate amount of purified water, and then perform a second homogenization treatment at 20 MPa using a high pressure homogenizer to further homogenize it and improve its fluidity, thus forming a stable water-in-oil liquid emulsion with a milky white appearance.

[0104] Comparative Example 1:

[0105] Compared with Example 1, the difference lies in the acidification temperature and method in step (2): after the system temperature is lowered to 45°C, a natural organic acid conditioning solution is added and mixed by conventional stirring. The rest are the same.

[0106] Comparative Example 2:

[0107] Compared with Example 1, the difference lies in the cooling method of step (4): the two-stage cooling process is cancelled, and the material is naturally cooled to 25°C while being stirred. All other aspects are the same.

[0108] Comparative Example 3:

[0109] Compared with Example 1, the difference lies in the matrix ratio in step (1): the amount of isomaltooligosaccharide is reduced to 20 kg, while 35 kg of purified water is added to make up the total weight, and the rest are the same.

[0110] Comparative Example 4:

[0111] Compared with Example 1, the difference lies in the substitution of raw materials in step (1): the matrix precursor liquid obtained in Example 1 was replaced with an equal amount of purified water (i.e., without sodium laminarin and glycyrrhizic acid), and 1.5 kg of carrageenan was added as a thickener, while the rest were the same.

[0112] Test Example 1:

[0113] The experimental steps are as follows:

[0114] (1) The plant extract composition prepared in Example 1 was selected as the experimental group sample, and the sample prepared in Comparative Example 4 (using carrageenan to replace the core matrix) was selected as the control group sample.

[0115] (2) Use a rotary rheometer equipped with a Peltier temperature control system and select a stainless steel cone plate clamp with a diameter of 40 mm and a cone angle of 1°.

[0116] (3) Set the test temperature to a constant 25.0℃, take an appropriate amount of sample and place it in the center of the test platform, press down the clamp to the set gap, scrape off the excess sample overflowing from the edge, and apply a layer of low viscosity silicone oil to the edge to prevent moisture from evaporating during the test.

[0117] (4) Allow the sample to stand for 5 minutes to balance and eliminate the influence of shear history during the loading process.

[0118] (5) Perform amplitude scanning to determine the linear viscoelastic region (LVR) of the sample at a frequency of 1 Hz. Then perform frequency scanning (0.1 to 100 rad / s) within the LVR range (strain set to 1%) and record the storage modulus (G') and loss modulus (G'').

[0119] (6) Perform steady-state flow scanning, with the shear rate range set to 0.01–100 s. -1 Record the change in apparent viscosity with shear rate.

[0120] (7) Perform a three-stage thixotropic ring test (3ITT): the first stage is 0.1s -1 The shearing process is performed at a low shear rate for 60 seconds to simulate a static state; the second stage instantly increases the shear rate to 100 seconds. -1 It is maintained for 30 seconds to simulate a swallowing or pumping process; the third phase rapidly recovers to 0.1 seconds. -1 The shear rate was set and maintained for 180 seconds to monitor the structural recovery process.

[0121] The experimental results are shown in Table 1.

[0122] Table 1. Rheological parameter test results of Example 1 and Comparative Example 4:

[0123]

[0124] According to Table 1 and Figure 1 Analysis of the test data showed that the system constructed in Example 1 exhibited unique supramolecular network characteristics in rheological behavior, verifying the feasibility and superiority of the glycyrrhizic acid-sodium alginate interpenetrating network mechanism.

[0125] In terms of static viscoelasticity, the storage modulus (G') of Example 1 is much greater than the loss modulus (G''), and the loss tangent (tanδ) remains at a low level of 0.213, indicating that a strong gel network dominated by elasticity has formed within the system. This high-strength physical cross-linking structure can effectively suspend insoluble particles and oil droplets in the system, which is the physical basis for the product to remain homogeneous, stable, and non-stratified during long-term storage. In contrast, although Comparative Example 4 achieved a higher initial modulus (G' > 4500 Pa) by relying on the polymer chain entanglement of carrageenan, its excessive rigidity may lead to a rough texture and lack of smoothness.

[0126] Steady-state flow scanning results show that Example 1 exhibits an extremely wide shear-thinning range. When the shear rate increases from 0.01 s⁻¹... -1 Increase to 100s -1 At this point, its viscosity decreased by more than two orders of magnitude, attributed to the dissociation and orientation of the weak interactions between glycyrrhizic acid micelles and the alginate acid-induced gel network (a hydrogen-bonded network formed by protonated carboxyl groups) under a shear field. This property endows the product with excellent processing and pumpability, as well as a smooth texture when consumed.

[0127] The most crucial difference lies in the thixotropic recovery performance. After undergoing high-speed shear failure, Example 1 exhibited a structural recovery rate of up to 94.2% within 60 seconds of rest, demonstrating intelligent response characteristics of instantaneous liquefaction and rapid reconstruction. This confirms the controlled self-assembly mechanism proposed in this invention, where the network nodes are not permanently covalently connected but rather based on reversible supramolecular self-assembly. When the external force is removed, the dispersed glycyrrhizic acid micelles and alginate segments can rapidly rebound and re-anchor under thermodynamic drive. In contrast, Comparative Example 4 showed a recovery rate of only 58.3% after 60 seconds, indicating that the re-entanglement process of the molecular chains in the traditional polymer network formed by carrageenan is slow and accompanied by a significant hysteresis effect after rupture. In practical applications, this hysteresis can prevent the product from spreading and forming a film on the gastric mucosa surface in a timely manner after swallowing, reducing the protective effect on the gastric wall and the bioadhesion of the active ingredients.

[0128] In summary, Example 1 successfully constructed a carrier system with both high structural strength and excellent thixotropy through specific physicochemical process control, and its microscopic kinetic performance is significantly better than that of traditional thickener systems.

[0129] Test Example 2:

[0130] The experimental steps are as follows:

[0131] (1) The plant extract composition prepared in Example 1 was selected as the experimental group, and the sample prepared in Comparative Example 3 (low sugar and high water formula) was selected as the control group. All samples were placed in a sealed container and equilibrated in a constant temperature environment of 25°C for 24 hours before testing.

[0132] (2) Moisture distribution was determined using a low-field nuclear magnetic resonance analyzer (LF-NMR, main magnetic field strength 0.5T, proton resonance frequency 21.3MHz). Approximately 2.0g of sample was weighed and placed in a 15mm diameter NMR glass tube. Transverse relaxation time (T2) decay curves were acquired using a CPMG pulse sequence. The number of repeated samplings (NS) was set to 16, the echo time (TE) to 0.25ms, and the number of echoes (NECH) to 5000. The T2 relaxation spectrum distribution was obtained by inversion.

[0133] (3) The phase transition enthalpy of water in the sample was determined using differential scanning calorimetry (DSC). 5-10 mg of sample was weighed and sealed in an aluminum crucible. Using an empty crucible as a reference, the sample was cooled to -60 °C at a rate of 10 °C / min under nitrogen flow protection (50 mL / min). The temperature was held constant for 5 minutes to allow the freezeable water in the sample to crystallize completely. Then, the temperature was increased to 20 °C at a rate of 5 °C / min. The endothermic curve during the heating process was recorded.

[0134] (4) Calculate the melting enthalpy (ΔH) based on the DSC endothermic peak area. Combine the melting enthalpy of pure water (334 J / g) and the water content of the sample to calculate the proportion of non-frozen water (i.e. strongly bound water) in the total water, thereby quantifying the matrix’s ability to bind water molecules.

[0135] The experimental results are shown in Table 2.

[0136] Table 2. Test results of moisture state and thermodynamic parameters of Example 1 and Comparative Example 3:

[0137]

[0138] According to Table 2 and Figure 2 The test data shows that the sugar concentration in the matrix formulation has a decisive influence on the moisture state of the system, confirming the existence of competitive hydration and latent acidification mechanisms.

[0139] As can be seen from the LF-NMR relaxation spectrum, the area of ​​peak T23, representing free water, in Example 1 is only 6.77%, and its relaxation time is significantly shifted to the left to 215.3 ms. This indicates that under the high osmotic pressure environment of 55% isomaltooligosaccharide, most water molecules are captured by the strong hydrogen bond network formed by the sugar hydroxyl groups and converted into T21 (bound water) and T22 (non-flowing water), with a total proportion of over 93%. This extremely scarce free water environment creates special kinetic conditions for the introduction of acid. When the acid is atomized into the system, due to the lack of a sufficient free solvent layer for rapid diffusion and complete dissociation, the acid-base reaction is confined to a microscopic region and proceeds slowly, thus avoiding the instantaneous precipitation of alginate caused by a sudden drop in local pH.

[0140] Conversely, Comparative Example 3, due to the reduced sugar concentration and the introduction of a large amount of exogenous water, had a free water ratio as high as 59.20% and a relaxation time extended to 842.1 ms, indicating that water molecules were in a highly active state. In this water-rich environment, once the acid solution was added, it would rapidly diffuse and completely ionize, causing the polymer chains to instantly protonate and undergo disordered aggregation, making it impossible to form a uniform gel network.

[0141] DSC thermodynamic data further corroborate this conclusion. The enthalpy of melting (ΔH) of Example 1 was only 14.32 J / g, and the calculated unfrozen water content was as high as 86.4%. Although this value is slightly lower than the total amount of bound water and immobile water determined by LF-NMR (93.23%), indicating that a small portion of the weakly bound water molecules still crystallized under cryogenic conditions, overall this means that even under cryogenic conditions of -60°C, the vast majority of water molecules in the system cannot form ice crystal lattices due to strong interactions with the matrix. This antifreeze property essentially reflects that water molecules are firmly locked in the supramolecular network of sugar-protein-polysaccharide, losing the freedom to participate in violent chemical reactions as a solvent. The huge endothermic peak (138.65 J / g) in Comparative Example 3 reveals the presence of a large amount of freezeable free water.

[0142] In summary, Example 1 constructs a high-concentration competitive hydration environment, transforming water molecules in the system from a solvent state to a structural state. This regulation of physical state is a key prerequisite for achieving latent acidification and subsequent controlled self-assembly, ensuring the uniformity of the final product's texture and the stability of its structure.

[0143] Test Example 3:

[0144] The experimental steps are as follows:

[0145] (1) Prepare the finished products prepared in Examples 1 to 4 as the experimental group, and the samples prepared in Comparative Examples 1 to 4 as the control group. All samples were placed in a constant temperature environment of 25°C for 48 hours before testing to eliminate thermal history differences.

[0146] (2) Centrifugal stability test: Take about 10.0g of each group of samples and place them in centrifuge tubes. Set the centrifuge speed to 4000rpm (relative centrifugal force of about 2500×g) and centrifuge for 30 minutes. After taking them out, observe whether there is layering, precipitation or oil-water separation. Remove the liquid that has separated from the upper layer (if any), weigh it again, and calculate the centrifugal water separation rate (%) as the evaluation index of physical stability.

[0147] (3) Total texture analysis (TPA) was performed using a texture analyzer. A P / 0.5R (0.5-inch) cylindrical probe was selected, the test mode was set to TPA, the pre-test rate, test rate and post-test rate were all 1.0 mm / s, the trigger force was 5.0 g, the target deformation was set to 30%, and the interval between two compressions was 5.0 s.

[0148] (4) Each group of samples was measured in parallel 5 times. The instrument software automatically calculated the hardness (the maximum peak force of the first compression), adhesion (the absolute value of the negative area of ​​the first compression return, reflecting the degree of stickiness) and cohesion (the ratio of the area of ​​the second compression to the area of ​​the first compression, reflecting the internal bonding force).

[0149] The experimental results are shown in Table 3.

[0150] Table 3. Test results of physical stability and textural properties of each group of samples:

[0151]

[0152] The data in Table 3 reveals the decisive influence of process parameters on the microstructure and macrotexture of the final product, demonstrating the unique advantages of the latent acidification-two-stage cooling process used in this invention in constructing high-performance carrier systems.

[0153] The data from Examples 1-4 are highly concentrated in the ideal region of high cohesion, low water separation rate, and moderate hardness. Their centrifugal water separation rates are all below 0.15%, and their cohesion remains above 0.85. This indicates that through latent acidification at high temperatures and subsequent controlled self-assembly, a uniformly distributed and dense interpenetrating network (IPN) is formed within the system. This network structure not only effectively locks in water and oil phases and resists phase separation under strong centrifugal force, but also imparts suitable hardness (160-210 g) and low adhesiveness (10-16 g·s) to the paste. Sensoryly, it is easy to apply and does not stick to teeth, solving the common problems of residue and stickiness in traditional paste products.

[0154] In contrast, Comparative Example 1 (low-temperature acidification) exhibited an abnormally high hardness of 310.5 g and a water separation rate of 4.85%, with a significant decrease in cohesion. This is because at a low temperature of 45°C, the macroscopic viscosity of the system increased significantly, hindering the rapid diffusion and homogenization of the acid at the microscopic scale, resulting in excessively high acid concentrations in localized areas. This non-uniform acidification environment triggered intense localized gelation reactions, leading to the formation of microscopic gel clumps invisible to the naked eye. These clumps disrupted the continuity of the overall network, making it easier for water to seep out from structural gaps, and also causing uneven texture.

[0155] Although Comparative Example 2 (natural cooling) did not exhibit severe delamination, its cohesiveness (0.61) was significantly lower than that of the Example Group. This confirms the necessity of the rapid cooling stage in the two-stage cooling process. During natural cooling, the temperature crosses the gel transition zone too slowly, resulting in inconsistent assembly rates of polymer chains in different regions. This leads to a loose network with many defects, which cannot provide sufficient internal binding force.

[0156] Comparative Example 4 (carrageenan substitute), while exhibiting excellent physical stability (0% water separation), had textural properties that deviated entirely from the palatable range. Its high hardness of 580.6 g and adhesiveness of 125.8 g·s resulted in a jelly-like, stiff texture and extremely strong stickiness. This, in turn, demonstrates that the supramolecular self-assembled network based on glycyrrhizic acid-sodium alginate of this invention can respond to shear forces while maintaining both stability and palatability.

[0157] Test Example 4:

[0158] The experimental steps are as follows:

[0159] (1) Fresh finished products prepared in Example 1 and Comparative Example 2 were selected as test objects. Three different batches were randomly selected from each group of samples, and each batch was sampled three times, for a total of 18 test samples.

[0160] (2) Determination of 5-HMF (5-hydroxymethylfurfural): Weigh 2.0 g of the sample, add 25 mL of ultrapure water to dissolve, extract by sonication for 15 minutes, centrifuge, collect the supernatant and filter through a 0.45 μm microporous membrane. High-performance liquid chromatography (HPLC) was used for detection. A C18 column (250 mm × 4.6 mm, 5 μm) was selected, the mobile phase was methanol-water (10:90), the flow rate was 1.0 mL / min, and the detection wavelength was set to 284 nm. The content of 5-HMF in the sample (mg / kg) was calculated by the external standard method to characterize the Maillard reaction degree and glycosyl degradation during processing.

[0161] (3) Determination of the retention rate of thermosensitive active ingredients: The thermosensitive plant extracts added to the formula (with ginsenoside Rg1 as the marker thermosensitive ingredient) were used as the indicator. 1.0 g of sample was accurately weighed, 25 mL of methanol was added, and the sample was extracted by ultrasonication for 30 minutes. After filtration, the sample was analyzed by HPLC. The mobile phase was acetonitrile-0.05% phosphoric acid aqueous solution gradient elution, and the detection wavelength was 203 nm.

[0162] (4) Data calculation: The theoretical content was calculated based on the amount of raw materials input, and the ratio of the measured content to the theoretical content was recorded as the retention rate (%). At the same time, the duration of the matrix system being in the high temperature range above 60°C during the preparation process of each group of samples was recorded to help analyze the influence of thermal history on chemical stability.

[0163] The experimental results are shown in Table 4.

[0164] Table 4. Test results of chemical stability indicators for Example 1 and Comparative Example 2:

[0165]

[0166] The test results in Table 4 reveal the significant advantages of the two-stage cooling process in chemical steady-state control and confirm the protective effect of the process parameters on the thermosensitive plant extract system.

[0167] From the perspective of 5-HMF content, the average content of Example 1 was only 4.22 mg / kg, which is at an extremely low background level, while the content of Comparative Example 2 surged to 28.85 mg / kg, an increase of nearly 7 times. This huge difference is directly related to the thermal history of the two: Example 1, through first-stage rapid cooling, lowered the material temperature from 70°C to 45°C in a very short time, controlling the high-temperature exposure time of the main process to within 40 minutes, and quickly leaving the sensitive temperature zone (>60°C) where the Maillard reaction rate is fastest. In this temperature zone, the condensation reaction of reducing sugars and amino acids follows the Arrhenius equation, and the reaction rate increases exponentially for every 10°C increase in temperature. Comparative Example 2 used natural cooling, and the material's residence time in the dangerous hot zone was on average more than 140 minutes. The additional 100 minutes of heat accumulation induced a severe non-enzymatic browning reaction, which is completely consistent with the phenomenon of darkening color and browning observed in the macroscopic observation of the Comparative Example 2 sample.

[0168] Regarding the retention rate of active ingredients, Example 1 demonstrated excellent carrying capacity for heat-sensitive substances, with an average retention rate of Rg1 as high as 98.48%, achieving almost non-destructive processing. In contrast, the retention rate of Comparative Example 2 decreased to 81.99%, meaning that nearly 20% of the active ingredients underwent thermal degradation or hydrolysis during the prolonged cooling process. This degradation not only wastes raw materials but may also alter the efficacy or safety of the product due to the formation of degradation products.

[0169] In summary, the dual-stage cooling strategy proposed in this invention is not merely a physical cooling method, but rather a technology for controlling chemical reaction kinetics. By precisely controlling the temperature-time curve, this process kinetically isolates the high-temperature sterilization and low-temperature assembly stages. While ensuring microbial safety, it maximizes the freezing of the system's chemical state, thereby solving the long-standing technical problems of high heat loss of active ingredients and difficulty in controlling browning in traditional herbal paste products.

[0170] Test Example 5:

[0171] The experimental steps are as follows:

[0172] (1) Preparation of simulated digestive fluid: Prepare simulated gastric juice (SGF), adjust the pH to 1.2 with dilute hydrochloric acid, and add pepsin (10g / L); prepare simulated intestinal juice (SIF), adjust the pH to 6.8 with potassium dihydrogen phosphate solution, and add trypsin (10g / L).

[0173] (2) Sample loading: Accurately weigh 5.0 g of each of the samples prepared in Example 1 and Comparative Example 4, place them in a dialysis bag with a molecular weight cutoff of 3500 Da, and tie both ends tightly to serve as a release unit.

[0174] (3) Gastric stage release (0-2 hours): Immerse the dialysis bag in a dissolution cup containing 100 mL of simulated gastric fluid, place it in a constant temperature shaker, set the temperature to 37±0.5℃ and the rotation speed to 100 rpm. At time points of 0.5, 1.0 and 2.0 hours, respectively, 5.0 mL of medium solution is aspirated and immediately replenished with an isothermal and equal volume of blank medium.

[0175] (4) Intestinal stage release (2-8 hours): After the gastric stage, remove the dialysis bag, rinse the surface with a small amount of distilled water, and immediately transfer it to a dissolution vessel containing 100 mL of simulated intestinal fluid to continue the release experiment. Samples were taken at 2.5, 3.0, 4.0, 6.0, and 8.0 hours, and an equal amount of blank medium was added.

[0176] (5) Content determination and calculation: The absorbance of total flavonoids in the sample solution at each time point was determined by ultraviolet-visible spectrophotometry (rutin as reference, detection wavelength 510 nm), and the cumulative release rate (%) was calculated. The formula for calculating the cumulative release rate needs to be corrected for the dilution effect caused by volume displacement.

[0177] The experimental results are shown in Table 5.

[0178] Table 5. Cumulative release rate data of Example 1 and Comparative Example 4 under simulated digestion conditions:

[0179]

[0180] Table 5 shows the in vitro simulated digestion data, which demonstrates the response behavior of different carrier systems under physiological pH conditions, confirming that the glycyrrhizic acid-sodium alginate interpenetrating network constructed in this invention has significant pH response characteristics.

[0181] In the first 2 hours of simulated gastric fluid (pH 1.2), Example 1 exhibited an extremely low cumulative release rate (only 11.32%). This phenomenon is attributed to the system's unique protonation self-protection mechanism. Under strong acid conditions, the carboxyl groups on the sodium alginate molecular chain undergo protonation to transform into alginic acid, leading to polymer chain contraction and the formation of a dense, insoluble gel layer. Simultaneously, the glucuronic acid groups in the glycyrrhizic acid molecule exhibit enhanced hydrophobicity under acidic conditions, further compressing the micelle structure. This dual contraction effect constructs a physical barrier on the carrier surface, effectively blocking the diffusion of internal active ingredients (such as total flavonoids) into the external acidic medium, thereby preventing premature release and degradation of acid-sensitive components in the stomach.

[0182] In contrast, Comparative Example 4 (carrageenan system) exhibited a release rate as high as 48.65% in the stomach, demonstrating a significant burst release effect. This is because carrageenan gel primarily relies on physical entanglement to maintain its structure and lacks a specific contraction response to pH. Under the dilution and mechanical agitation of gastric juice, its gel network pores remain open, leading to rapid diffusion and loss of small molecule active ingredients down the concentration gradient. This not only reduces drug bioavailability but may also cause side effects due to local irritation of the gastric mucosa by high drug concentrations.

[0183] When the sample was transferred to simulated intestinal fluid (pH 6.8), the release behavior of Example 1 underwent a dramatic reversal. As the ambient pH increased, the carboxyl groups in the alginate gel layer deprotonated and exchanged ions with sodium and potassium ions in the medium, causing the gel network to rapidly swell and disintegrate; simultaneously, the solubility of glycyrrhizic acid micelles increased. This structural disintegration triggered the rapid release of the active ingredient, with a significantly accelerated release rate during the intestinal phase (2–8 hours), ultimately reaching a cumulative release rate of 92.15%. This gastric-closed, intestinal-open release pattern highly aligns with the physiological needs of human digestion and absorption, ensuring that the active ingredient is primarily released in the small intestine, the main site of absorption.

[0184] In summary, Example 1 is not a simple physical mixture, but an intelligent delivery system with environmental awareness capabilities. Through molecular-level structural design, it successfully achieves spatiotemporally controlled release of active ingredients, demonstrating significantly superior protective efficacy and bioavailability compared to traditional physical thickener systems.

[0185] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A plant extract composition for relieving liver qi stagnation and nodules, characterized in that, The composition exhibits shear-thinning thixotropic properties and pH-responsive release characteristics, and is made from raw materials comprising the following parts by weight: 45-60 parts of isomaltooligosaccharide; 20-30 parts of matrix precursor fluid derived from kelp and licorice; 5-10 parts of lipophilic concentrates derived from peach kernels and dried ginger; 8-15 parts of natural organic acid regulator derived from dried tangerine peel and citron; 4-8 parts of thermosensitive active liquid derived from dandelion and ginseng; The composition contains an interpenetrating network structure of glycyrrhizic acid and alginate formed through an in-situ reaction between the matrix precursor liquid and the natural organic acid conditioning liquid.

2. The plant extract composition for relieving liver qi stagnation and nodules according to claim 1, characterized in that, The matrix precursor liquid is a liquid with a relative density of 1.12 to 1.15 prepared by water extraction, centrifugation and concentration of the following raw materials in parts by weight: 15 to 20 parts kelp, 12 to 15 parts licorice, 10 to 12 parts poria cocos and 5 to 6 parts donkey-hide gelatin.

3. The plant extract composition for relieving liver qi stagnation and nodules according to claim 1, characterized in that, The lipophilic concentrate is an oily substance prepared by heating and reflux extraction of the following raw materials in parts by weight with 95% ethanol: 8 parts peach kernel, 5 parts dried ginger, 6 parts angelica, 5 parts Lindera leaf, 5 parts Angelica dahurica, and 1 part saffron.

4. The plant extract composition for relieving liver qi stagnation and nodules according to claim 1, characterized in that, The natural organic acid regulating liquid is a liquid with a pH of 3.1 prepared by extracting and concentrating the following raw materials in parts by weight with 60% ethanol: 8 parts dried tangerine peel, 8 parts citron, and 12 parts mulberry. The thermosensitive active liquid is a liquid prepared by hot soaking, extraction and concentration of the following raw materials in parts by weight: 8 parts dandelion, 4 parts ginseng, 6 parts platycodon, 8 parts polygonatum, 8 parts ophiopogon japonicus, 4 parts ganoderma lucidum and 1 part snow lotus culture.

5. The plant extract composition for relieving liver qi stagnation and nodules according to claim 1, characterized in that, The composition is an oil-in-water emulsion gel, wherein the lipophilic concentrate serves as the dispersed phase and is dispersed in droplet form in a continuous phase gel network composed of the isomaltooligosaccharide, matrix precursor liquid, natural organic acid conditioning liquid, and thermosensitive active liquid.

6. A method for preparing a plant extract composition for relieving liver qi stagnation and nodules as described in any one of claims 1-5, characterized in that, Includes the following steps: Step 1, matrix mixing and emulsification: Mix isomaltooligosaccharide, matrix precursor liquid and lipophilic concentrate, and shear emulsify at a temperature of 75°C to 80°C to form an emulsified matrix system. Step 2, instantaneous acidification initiation: Maintain the temperature at 75°C to 80°C, atomize the natural organic acid conditioning liquid into the emulsion matrix system, and continue shearing under turbulent conditions to construct a primary gel network; Step 3, thermosensitive component composite: lower the system temperature to 68℃ to 72℃, add thermosensitive active liquid, and stir at low speed to mix evenly; Step 4, two-stage cooling and shaping: The material obtained in step 3 is subjected to programmed cooling. First, a rapid cooling stage is performed to fix the gel skeleton, and then a slow cooling stage is performed to room temperature to obtain the final product.

7. The preparation method according to claim 6, characterized in that, The specific parameters for the two-stage cooling and shaping process described in step 4 are as follows: First stage: Reduce the material temperature from 68℃~72℃ to 42℃~48℃ at a rate of 2℃~6℃ per minute; Second stage: Reduce the material temperature from 42℃ to 48℃ to 20℃ to 25℃ at a rate of 0.5℃ to 1.5℃ per minute.

8. The preparation method according to claim 6, characterized in that, In step 1, the high-shear emulsifier is set to a speed of 3500-5500 rpm and a constant-temperature shearing time of 10-20 minutes. In step 2, the atomization spraying is carried out through a pressure atomizing tank and an atomizing nozzle, and the acid flow rate is controlled at 0.8-1.5 kg per minute.

9. The preparation method according to claim 6, characterized in that, The matrix precursor solution used in step 1 is prepared by the following method: Take kelp, licorice, poria cocos and donkey-hide gelatin, grind them into powder, add purified water, and add an alkaline regulator to adjust the pH value to 8.2-8.5; heat to extract, filter, centrifuge the filtrate at 10000-12000 rpm to remove insoluble matter; concentrate the supernatant under reduced pressure to obtain the final product.

10. The use of a plant extract composition for relieving liver qi stagnation and nodules as described in any one of claims 1-5 in the preparation of food or health food, characterized in that, The dosage forms of the food or health food include pastes, pills, powders, granules, tablets, capsules, oral liquids, beverages, emulsions, or gels.

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