Oral liquid capable of expelling stones and clearing toxins and preparation process thereof

Abstract

The application relates to the medical technology field and discloses an oral liquid capable of easily expelling stones and clearing toxins and a preparation process thereof. The raw materials of the oral liquid include chicken gizzard suet, dandelion, houttuynia cordata, sea golden sand, plantain, corn silk, money grass, corydalis, licorice and oligofructose with a specific polymerization degree. The preparation process comprises grouping extraction of the raw materials, purification of the chicken gizzard suet by using concentration with forced circulation and bottom feeding type jet flow, pressure filtration of the sea golden sand by using the endogenous fiber of the houttuynia cordata to construct a filter aid skeleton, and finally constant-temperature liquid preparation and sterilization by using a micropore filter membrane to obtain the finished product. Oligofructose is introduced into traditional Chinese medicine to promote proliferation of intestinal oxalic acid degrading bacteria, and plant components are used to block stone generation from a metabolic source; specific fluid mechanics separation and non-thermal sterilization processes solve the problems of protein aggregation and micropore blockage of microspores, and the configuration stability of heat-sensitive medicinal components and prebiotic molecules is maintained.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to an oral liquid that facilitates the expulsion of stones and detoxification, and its preparation process. Background Technology

[0002] In recent years, the fast pace of work and irregular eating habits have led to an increase in the incidence of kidney stones. Traditional Chinese medicine (TCM) has been widely used in regulating the body's condition and treating kidney stones. Existing oral liquids containing TCM herbs for clearing heat and dampness, dissolving stones, and expelling them have received positive clinical feedback in promoting stone expulsion and relieving urinary tract inflammation. In the preparation process of these oral liquids, the industry generally adopts a process of mixing various TCM herbs, followed by decoction extraction, filtration, concentration, conventional alcohol precipitation, and high-temperature sterilization. This method, due to its wide applicability and ease of operation, has become the mainstream technology in the field of TCM processing.

[0003] Existing oral liquids for kidney stone removal have certain limitations in their pathways of action. Conventional formulations mainly rely on the diuretic and antispasmodic effects of plant-based medicinal ingredients, with intervention primarily focused on the physical expulsion stage after stone formation. This mode of action is insufficient to inhibit stone formation at the metabolic level, especially failing to effectively intervene in the absorption and deposition of oxalate in the intestines, thus lacking the ability to block oxalate metabolic cycles and improve the body's internal microecological environment.

[0004] In the production and preparation process, conventional mixed extraction and uniform processing techniques ignore the differences in physicochemical properties between different medicinal material components. When processing animal-derived medicinal materials rich in protein or plant-derived medicinal materials containing microspores, conventional processes can easily cause protein aggregation, which can then encapsulate free active ingredients, or cause fine particles to clog filter materials, thus affecting solid-liquid separation efficiency and extraction purity. At the same time, conventional high-temperature sterilization and heat-concentration environments can easily lead to the degradation of heat-sensitive active substances and may also damage the molecular configuration of specific macromolecular prebiotics in the formula, which to some extent limits the overall efficacy of the oral liquid.

[0005] Therefore, the present invention provides an oral liquid that facilitates the expulsion of stones and detoxification, and its preparation process, in order to overcome the shortcomings of the prior art. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides an oral liquid that facilitates the expulsion of stones and detoxification, along with its preparation process. This solves the problems of existing oral liquids for expelling stones and clearing heat failing to block the absorption and deposition of oxalate at the source of intestinal metabolism, and the fact that conventional high-temperature extraction and sterilization processes easily lead to the degradation of heat-sensitive active ingredients and damage to the spatial structure of macromolecular prebiotics.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] In a first aspect, the present invention provides an oral liquid that facilitates the expulsion of stones and detoxification, employing the following technical solution:

[0009] An oral liquid that facilitates the expulsion of stones and detoxification is made from the following ingredients in parts by weight: 10-15 parts chicken gizzard lining; 6-8 parts dandelion; 5-6 parts houttuynia cordata; 10-15 parts lygodium japonicum; 5-7 parts plantain; 10-15 parts corn silk; 15-20 parts lysimachia christinae; 8-10 parts corydalis yanhusuo; 2-4 parts licorice; 2-4 parts fructooligosaccharides; 0.05-0.1 parts stevioside; and 0.1-0.3 parts sodium benzoate.

[0010] By adopting the above technical solution, the oral liquid formulation of the present invention introduces a specific ratio of fructooligosaccharides. Lysimachia christinae, Lygodium japonicum, and chicken gizzard lining synergistically promote the dissolution and excretion of stones; combined with the heat-clearing effects of dandelion and houttuynia cordata, it aims to reduce urinary tract mucosal inflammation caused by stones; Corydalis yanhusuo is used to relieve smooth muscle spasms and pain. The fructooligosaccharides in the formulation exhibit certain anti-hydrolysis properties in the digestive tract environment. After being incompletely digested and entering the colon, they are typically used as a substrate specifically by oxalate-degrading bacteria such as formic acid-producing oxalobacterium in the intestine. By altering the intestinal microecology, this promotes the degradation reaction of oxalate in the intestine, thereby leading to a decrease in serum oxalate concentration and urinary oxalate excretion, which helps inhibit the formation of calcium oxalate stones in the metabolic process.

[0011] Preferably, the fructooligosaccharide is a fructooligosaccharide with a degree of polymerization of 3 to 5 and containing β2-1 glycosidic bonds; in the oral liquid, the mass concentration of the fructooligosaccharide is 2.82-2.94 mg / mL, and the mass concentration of the low molecular weight monosaccharides and disaccharides is 0.32-0.38 mg / mL.

[0012] By employing the above technical solution, oligofructose with β2-1 glycosidic bonds and a degree of polymerization of 3 to 5 exhibits structural characteristics that make it relatively difficult to be hydrolyzed by gastric acid and α-amylase and sucrase secreted by the human intestinal mucosa. After reaching the colon, this configuration primarily exerts its effects through the following biochemical pathways:

[0013] Step 1: Specific carbon source supply. Fructooligosaccharides are taken up by transport proteins on the surface of *Oxalis formic acid oxidase*, activating the expression of intracellular catabolism-related enzyme systems and promoting the logarithmic growth phase of the bacterial community.

[0014] Step Two: Oxalate Degradation and Metabolism. The proliferating oxalate-degrading bacteria secrete oxalate-coenzyme A transferase and formyl-CoA transferase, catalyzing the decarboxylation of oxalate in the intestine. The reaction equation is as follows:

[0015] Oxalate + Formicoic acid-producing Oxalate Bacillus enzyme system → Formate + Carbon dioxide;

[0016] Step 3: Concentration gradient diffusion. As free oxalate in the intestinal lumen is consumed, a concentration gradient of oxalate is formed inside and outside the intestine, prompting serum oxalate to be secreted back into the intestinal lumen and continuously degraded.

[0017] In addition, controlling the concentration of fructooligosaccharides in the finished oral liquid at 2.82-2.94 mg / mL and the concentration of low molecular weight monosaccharides and disaccharides from thermal degradation products below 0.38 mg / mL can control the excessive proliferation of non-target bacteria caused by high monosaccharide and disaccharide content, thereby maintaining the competitive state of oxalic acid degrading bacteria in this microecological environment.

[0018] Preferably, the oral liquid is an oral liquid prepared by sterilization filtration using a microporous filter membrane with a pore size of 0.22 μm.

[0019] By adopting the above technical solution and using physical pore size interception sterilization technology, compared with the conventional heat treatment process, the probability of Maillard reaction and glycosidic bond breakage caused by high temperature in the system is reduced. This is beneficial to retain the oligofructose configuration with a degree of polymerization of 3 to 5 in the formula, and to a certain extent maintains the bioactivity of plant effective components and polypeptides in chicken gizzard.

[0020] Secondly, the present invention provides a preparation process for an oral liquid that facilitates the expulsion of stones and detoxification, employing the following technical solution:

[0021] A preparation process for an oral liquid that facilitates the expulsion of stones and detoxification includes the following steps:

[0022] S1: Weigh the raw materials by weight: 10-15 parts chicken gizzard lining, 6-8 parts dandelion, 5-6 parts houttuynia cordata, 10-15 parts lygodium japonicum, 5-7 parts plantain, 10-15 parts corn silk, 15-20 parts lysimachia christinae, 8-10 parts corydalis yanhusuo, 2-4 parts licorice, 2-4 parts fructooligosaccharides, 0.05-0.1 parts steviol glycoside, and 0.1-0.3 parts sodium benzoate;

[0023] S2: Chicken gizzard lining, dandelion, plantain, corn silk, lysimachia christinae, corydalis, and licorice are pulverized; houttuynia cordata is coarsely pulverized to control the plant fiber length distribution within the range of 0.5-4mm; lygodium japonicum is left untreated.

[0024] S3: Soak the raw materials processed in step S2 in room temperature water;

[0025] S4: Dandelion, Corydalis and corn silk were mixed as group A, water was added and decocted for extraction, the filtrates were filtered and combined, concentrated under reduced pressure, vortexed and ethanol was sprayed on the liquid surface for alcohol precipitation, refrigerated, the supernatant was taken to recover the ethanol and concentrated to obtain concentrate A.

[0026] S5: Mix Lysimachia christinae, Glycyrrhiza uralensis and Plantago asiatica as Group B, add water to decoct and extract, filter and combine the filtrates, concentrate under reduced pressure, perform vortex stirring and spray ethanol above the liquid surface for alcohol precipitation, refrigerate, take the supernatant to recover ethanol and concentrate to obtain concentrate B.

[0027] S6: Chicken gizzard lining was treated as a separate group C. It was boiled in water for extraction, filtered and combined. The filtrates were concentrated under reduced pressure using an externally heated vacuum concentrator with a forced circulation pump. The concentrated material was then introduced into an alcohol precipitation tank. Ethanol was injected from bottom to top through a Venturi jet injector at the bottom. The tank was refrigerated, and the supernatant was collected to recover the ethanol and concentrate it to obtain concentrate C.

[0028] S7: Mix Lygodium japonicum with coarsely crushed Houttuynia cordata as Group D, add water and decoct to extract; pump the slurry of the extract and the residue into a plate and frame filter press, use the first pressure for initial filtration, form a plant fiber filter aid layer on the surface of the filter cloth, then increase the pressure to a second pressure higher than the first pressure to complete the filtration, and combine the filtrates; concentrate the filtrate under reduced pressure, spray ethanol above the liquid surface for alcohol precipitation, refrigerate, take the supernatant to recover the ethanol and concentrate to obtain concentrate D;

[0029] S8: Combine the obtained concentrates A, B, C, and D into a mixing tank, maintain the temperature in the mixing tank at 35-40℃, add fructooligosaccharides, steviol glycosides, and sodium benzoate to dissolve, and add purified water to make up the volume; pre-filter the drug solution through a microporous membrane with a pore size of 0.45μm, and then finely filter it through a microporous membrane with a pore size of 0.22μm, and dispense the finished product.

[0030] By adopting the above technical solutions, the process incorporates differentiated treatment based on the structural characteristics and physicochemical properties of each raw material. Specifically, considering that chicken gizzard contains a high amount of protein and colloidal substances, its extract is prone to foaming and adhering to the filter walls during concentration. Therefore, a vacuum concentration system with forced circulation and bottom-feed alcohol precipitation are used to reduce the aggregation and precipitation of effective components during the purification of high-protein materials. Furthermore, addressing the physical characteristic that Lygodium japonicum microspores easily penetrate or clog conventional filter media, co-extraction and pressure filtration are performed by adding coarsely crushed Houttuynia cordata containing fibers of a specific length. This alters the hydrodynamic state of the solid-liquid separation interface, thereby alleviating the pore-clogging phenomenon caused by fine powder. Finally, the combined materials are mixed at a constant temperature of 35-40℃ and sterilized using a membrane, which helps maintain the stability of the system's physicochemical properties.

[0031] Preferably, in step S6, the process of vacuum concentration using an externally heated vacuum concentrator with a forced circulation pump is as follows: the extract is concentrated under reduced pressure at 60-70°C. When the relative density reaches 1.15, the forced circulation pump is turned on, and the flow rate in the tube is controlled at 1.5-2.0 m / s until the relative density reaches 1.20-1.25, at which point the concentration is stopped. In step S6, the process of injecting ethanol from bottom to top through a venturi ejector at the bottom is as follows: 95% ethanol is injected into the bottom of the alcohol precipitation tank at a pressure of 0.2-0.4 MPa through the venturi ejector until the final ethanol volume concentration reaches 75%.

[0032] By adopting the above technical solution, the phase mixing state of chicken gizzard lining extract during alcohol precipitation was further optimized. Its hydrodynamic control mechanism is as follows:

[0033] Step 1: Kinetic Energy-Induced Concentration and Scale Prevention. When the relative density of the extract reaches 1.15, the apparent viscosity of the fluid increases, transitioning from a Newtonian fluid to a non-Newtonian fluid. At this point, the forced circulation pump is activated and the flow rate in the tube is controlled at 1.5-2.0 m / s. By increasing the Reynolds number of the fluid, the temperature and concentration boundary layer of the heated tube wall is disrupted, limiting the deposition of solute molecules on the tube wall and maintaining the progress of the concentration process.

[0034] Step Two: High-Shear Ethanol Precipitation by Jet. If high-density extracts are directly sprayed with ethanol onto the liquid surface, a high-concentration zone often forms at the contact interface, leading to irreversible protein aggregation and encapsulation of free components. This method uses a bottom-mounted Venturi jet injector to inject ethanol at a pressure of 0.2-0.4 MPa. The negative pressure generated by the constricted tube cross-section and the shear force of the high-speed jet allow for microscopic mixing of the high-viscosity concentrate and low-viscosity ethanol in a very short time. Under the high shear field, the proteins undergo conformational unfolding and slowly aggregate into a loose precipitate, which helps release the active pharmaceutical ingredients present in the liquid phase and increases the yield of the concentrate.

[0035] Preferably, in step S7, the first pressure is 0.1-0.2 MPa, the initial pressure filtration time is 10-15 min, the thickness of the plant fiber filter aid layer is 5-15 mm, the second pressure is 0.2-0.3 MPa, and in step S2, the houttuynia cordata is coarsely crushed and passed through a 10-20 mesh sieve, and the median diameter D50 of the obtained plant fiber length is 1-3 mm.

[0036] By employing the above technical solution, a filtration mechanism based on a spatial network of plant endogenous fibers was constructed to address the filtration resistance problem caused by microspores of Lygodium japonicum. The principle is explained as follows:

[0037] Step 1: Fiber Skeleton Construction. The houttuynia cordata is coarsely crushed, and its median diameter (D50) is controlled to be 1-3 mm, ensuring the retention of a large number of fibers composed of vascular bundles and thick-walled cells. When the slurry is pumped into the filter press, a low pressure of 0.1-0.2 MPa is applied. At this pressure, the drag force of the fluid on the solid particles is limited, and the long-chain fiber particles of houttuynia cordata overlap on the filter cloth surface, forming a highly porous and incompressible three-dimensional mesh structure, i.e., a fiber filter aid layer with a thickness of 5-15 mm.

[0038] Step Two: Spore Retention and High-Pressure Dehydration. When Lygodium japonicum microspores enter the aforementioned fiber mesh, they are retained within the pores of the framework, reducing the likelihood of direct contact with the bottom filter cloth pores. Due to the supporting role of the bottom framework, even if the feed pressure is subsequently increased to 0.2-0.3 MPa, the entire filter cake layer is not prone to significant compaction deformation, maintaining the capillary channels through which fluid passes. According to Darcy's law of filtration, this process improves the filtration constant and shortens the separation cycle without the addition of exogenous filter aids.

[0039] Preferably, in steps S4 and S5, the temperature for vacuum concentration is 60-70℃; the process of spraying ethanol above the liquid surface for alcohol precipitation is as follows: 95% ethanol is added through an atomizing nozzle under vortex stirring at a speed of 60-90 r / min; in step S4, the final ethanol volume concentration of group A alcohol precipitation is 70%; in step S5, the final ethanol volume concentration of group B alcohol precipitation is 65%; the refrigeration temperature is 0-4℃, and the refrigeration time is 12-24 h.

[0040] By employing the above technical solution, the extracts from groups A and B are combined with atomized ethanol spraying under vortex stirring at 60-90 r / min, promoting the formation of a relatively gentle concentration gradient of the extracts within the bulk liquid phase. Since the solubility of water-soluble polysaccharides, tannins, and impurities in groups A and B differs, endpoint ethanol volume concentrations of 70% and 65% are set, respectively. Furthermore, refrigeration at 0-4℃ reduces the system's kinetic energy, which facilitates the accelerated formation of crystal nuclei and flocculation sedimentation of supersaturated impurities, thereby improving separation efficiency.

[0041] Preferably, in step S8, the temperature inside the mixing tank is maintained at 35-40℃ for constant temperature cold mixing. The drug solution after volume adjustment is first pre-filtered through a microporous membrane with a pore size of 0.45μm, and then finely filtered through a microporous membrane with a pore size of 0.22μm.

[0042] By adopting the above technical solution, the impact of heat load is reduced during the preparation and sterilization stages. Controlling the solution preparation system at 35-40℃, which is below the activation energy required for the glycosidic bond breakage in fructooligosaccharide molecules, limits the thermal dissociation of fructooligosaccharides into free monosaccharides. Simultaneously, this specific temperature state reduces the hydrodynamic viscosity of the solution, which is beneficial for maintaining the filtration flux of the 0.45μm and 0.22μm dual-stage microporous membranes and reduces the risk of membrane module fouling and clogging.

[0043] This invention provides an oral liquid that facilitates the expulsion of stones and detoxification, along with its preparation process. It possesses the following beneficial effects:

[0044] 1. This invention introduces oligofructose with a degree of polymerization of 3 to 5 and containing β2-1 glycosidic bonds into the base of traditional Chinese medicine components such as Lysimachia christinae and chicken gizzard lining, forming a multi-pathway synergistic intervention. The plant extracts in the formula mainly promote the dissolution and excretion of stones and alleviate urinary tract inflammation, while the oligofructose with a specific structure, upon reaching the colon, serves as a carbon source substrate utilized by oxalate-degrading bacteria in the intestine, promoting bacterial proliferation and catalyzing the decarboxylation and degradation of oxalate in the intestine. This combined approach changes the traditional approach that relies solely on diuresis and antispasmodics, helping to reduce the concentration of oxalate in serum and urine from the intestinal metabolic stage and inhibiting the formation of calcium oxalate stones.

[0045] 2. This invention designs differentiated extraction and separation processes based on the physicochemical properties of different raw materials in the formula. For chicken gizzard lining, which contains a high amount of protein, a vacuum concentration with forced circulation and bottom-feed Venturi jet alcohol precipitation are used. The high shear force of the fluid improves the mixing state and reduces the encapsulation of free effective components by protein agglomeration. For Lygodium japonicum microspores, which easily clog filter media, co-extraction and step-pressure filtration are carried out by mixing in coarsely crushed Houttuynia cordata with a certain length of fiber. The endogenous fiber of the plant is used to construct a three-dimensional filter aid skeleton on the surface of the filter cloth, which traps microparticles and maintains fluid channels, thereby improving the purity of the material and the solid-liquid separation efficiency without adding exogenous filter aids.

[0046] 3. In the volume adjustment and sterilization stages of the medicinal solution, this invention employs a non-thermal treatment method combining constant temperature preparation at 35-40℃ with fine filtration using a 0.22μm microporous membrane. This process replaces conventional high-temperature thermal sterilization with the physical pore size retention of the membrane module, avoiding the risk of Maillard reactions and glycosidic bond breakage under heat. These treatment conditions limit the thermal dissociation reaction of fructooligosaccharides into low-molecular-weight monosaccharides and disaccharides, maintaining their specific molecular configuration, while also preserving the bioactivity of the plant-derived active ingredients and polypeptides in the formulation system. Attached Figure Description

[0047] Figure 1 This is a graph showing the relationship between the effective fructooligosaccharide and low molecular weight mono- and disaccharide concentrations of the present invention.

[0048] Figure 2 This is a typical HPLC chromatogram of residual oxalate in this invention. Detailed Implementation

[0049] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only 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 are within the scope of protection of the present invention.

[0050] 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.

[0051] The traditional Chinese medicine ingredients involved in the formulation of this invention—chicken gizzard lining, dandelion, houttuynia cordata, lygodium japonicum, plantain, corn silk, lysimachia christinae, corydalis yanhusuo, and licorice—are all commercially available processed medicinal materials conforming to the current edition of the *Pharmacopoeia of the People's Republic of China*. Fructooligosaccharides are commercially available conventional products, CAS number 308066-66-2, with an active ingredient purity ≥95wt%, of which fructooligosaccharide components with a degree of polymerization of 3-5 constitute the main part of the active ingredient. Stevioside is a commercially available conventional product, CAS number 57817-89-7, with a purity ≥90wt%. Sodium benzoate is a commercially available conventional product, CAS number 532-32-1, with a purity ≥99.0wt%. Ethanol is a commercially available conventional pharmaceutical-grade product with a concentration of 95vol%. Sterile water is commercially available pharmaceutical-grade sterile purified water conforming to the *Pharmacopoeia of the People's Republic of China*.

[0052] Unless otherwise specified, in the following examples, the "water addition multiple" for "decoction extraction" refers to the amount of water added each time, equivalent to the total weight of the corresponding herbal group. After the soaking process, the herbs, along with the soaking solution, enter the subsequent extraction process. During the first extraction, water is added to the corresponding water addition multiple. In the following examples and test cases, the relative density is the value measured at 60℃. Each sample in each test case was measured in triplicate; the data in the table are the average of the three measurements.

[0053] Example 1:

[0054] This embodiment provides an oral liquid that facilitates the expulsion of stones and detoxification, and its preparation process, including the following steps:

[0055] S1: Weigh the raw materials by weight: 12kg chicken gizzard lining, 7kg dandelion, 5.5kg houttuynia cordata, 12kg lygodium japonicum, 6kg plantain, 12kg corn silk, 18kg lysimachia christinae, 9kg corydalis yanhusuo, 3kg licorice, and weigh out 3kg fructooligosaccharides, 0.08kg steviol glycosides, and 0.2kg sodium benzoate.

[0056] S2: Differentiated pretreatment of Chinese medicinal materials. Chicken gizzard lining, dandelion, plantain, corn silk, lysimachia christinae, corydalis yanhusuo, and licorice were pulverized using a hammer mill and passed through a 70-mesh sieve to obtain fine powder; Lygodium japonicum was not pulverized; Houttuynia cordata was coarsely pulverized using a blade mill and passed through a 15-mesh sieve, controlling the obtained plant fiber length D50 to be approximately 2mm, with the fiber length mainly distributed in the range of 1-3mm, thereby preserving the long chain structure of plant fibers that have a spatial support function.

[0057] S3: Soaking the herbs. Add 6 times their weight of room temperature water to each pre-treated herb for static soaking. Chicken gizzard lining is soaked separately for 30 minutes, while the other herbs are soaked for 1.5 hours. After soaking, each herb, along with the soaking solution, is then introduced into the subsequent extraction process of the corresponding group.

[0058] S4: Extraction and Concentration of Group A with Alcohol Precipitation. Dandelion, Corydalis, and corn silk were mixed as Group A. Water equivalent to nine times the total weight of the group's herbs was added, and the mixture was decocted three times at a gentle boil, 0.8 hours each time. The three extracts were filtered through a 150-mesh filter cloth, and the filtrates were combined and introduced into a double-effect concentrator. The mixture was concentrated under reduced pressure at 65℃ and a vacuum of -0.07 MPa until a relative density of 1.13 was achieved. This was then transferred to an alcohol precipitation tank, and a vortex mixer was started at 75 r / min. Simultaneously, 95 vol% ethanol was sprayed above the liquid surface through a mist nozzle until the final ethanol concentration reached 70 vol%. The mixture was refrigerated at 2℃ for 18 hours. The supernatant was collected, filtered to remove precipitate, and the ethanol was recovered under reduced pressure and concentrated to a relative density of 1.18 to obtain concentrate A.

[0059] S5: Extraction and Concentration of Group B with Alcohol Precipitation. A mixture of Lysimachia christinae, Glycyrrhiza uralensis, and Plantago asiatica was used as Group B. Water, equivalent to nine times the total weight of the herbs in this group, was added for each extraction, and the mixture was decocted twice, 0.8 hours each time. The filtrates were combined and concentrated under reduced pressure at 65°C to a relative density of 1.10. The concentrate was then transferred to an alcohol precipitation tank, and 95 vol% ethanol was added using the same vortex stirring and atomized spraying method to adjust the final concentration to 65 vol%. The mixture was refrigerated at 2°C for 18 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density determination, the concentration was adjusted to 1.18 by reduced pressure concentration or by adding purified water to obtain concentrate B.

[0060] S6: Extraction and Concentration of Group C (Alcohol Precipitation). Chicken gizzard lining was used as Group C. It was extracted four times, each time by decoction with water equivalent to nine times the weight of the chicken gizzard lining, for 0.8 hours each time. The filtrates were then combined. A vacuum concentrator with a forced circulation pump and external heating was used for concentration under reduced pressure at 65°C. When the relative density reached 1.15, the forced circulation pump was activated, and the flow rate in the tubing was controlled at 1.7 m / s until the relative density reached 1.22, at which point concentration was stopped. This high-density concentrate was then introduced into an alcohol precipitation tank. 95 vol% ethanol was injected from bottom to top through a venturi jet injector at 0.3 MPa pressure, creating strong shear mixing until the final concentration reached 75 vol%. The mixture was refrigerated at 2°C for 18 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density measurement results, the relative density was adjusted to 1.18 by reduced pressure concentration or by adding purified water, yielding concentrate C.

[0061] S7: Extraction and Concentration of Group D with Alcohol Precipitation. Group D consisted of a mixture of Lygodium japonicum and coarsely crushed Houttuynia cordata. Water, equivalent to nine times the total weight of the group's herbs, was added for decoction twice, each time for 0.8 hours. The extract and residue were mixed and pumped into a plate and frame filter press. The initial filtration pressure was controlled at 0.15 MPa and maintained for 12 minutes, forming a 10 mm thick loose fibrous filter aid layer on the filter cloth surface. The filtration pressure was then increased to 0.25 MPa to complete the full filtration, and the filtrates were combined. The solution was concentrated under reduced pressure at 65℃ to a relative density of 1.16. 95 vol% ethanol was added via spraying until the final ethanol concentration reached 60 vol%. The solution was refrigerated at 2℃ for 18 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density measurement results, the solution was concentrated under reduced pressure or purified water was added to adjust the relative density to 1.18, yielding concentrate D.

[0062] S8: Constant Temperature Preparation and Aseptic Filling. Combine the obtained concentrates A, B, C, and D into a mixing tank. Turn on the jacket cooling water to maintain the temperature of the mixture at a constant 37°C. At this temperature, add the prescribed amounts of fructooligosaccharides, steviol glycosides, and sodium benzoate. After stirring and dissolving evenly, add sterile purified water to a final volume of 1000L. Pre-filter the final volume solution through a 0.45μm microporous membrane, then perform sterile fine filtration through a 0.22μm sterile-grade microporous membrane. Aseptically dispense the solution into oral liquid bottles within a Class 100 clean area to obtain the finished product.

[0063] Example 2:

[0064] This embodiment provides an oral liquid that facilitates the expulsion of stones and detoxification, and its preparation process, including the following steps:

[0065] S1: Weigh the raw materials by weight: 10kg chicken gizzard lining, 6kg dandelion, 5kg houttuynia cordata, 10kg lygodium japonicum, 5kg plantain, 10kg corn silk, 15kg lysimachia christinae, 8kg corydalis yanhusuo, 2kg licorice, and weigh out 3kg fructooligosaccharides, 0.05kg steviol glycosides, and 0.1kg sodium benzoate.

[0066] S2: Differentiated pretreatment of Chinese medicinal materials. Chicken gizzard lining, dandelion, plantain, corn silk, lysimachia christinae, corydalis yanhusuo, and licorice were pulverized and passed through a 60-mesh sieve to obtain fine powder; Lygodium japonicum was not pulverized; Houttuynia cordata was coarsely pulverized and passed through a 20-mesh sieve, and the length D50 of the obtained plant fibers was controlled to be about 1 mm, with the fiber length mainly distributed in the range of 0.5-1.5 mm.

[0067] S3: Soaking the herbs. Add 5 times the weight of each herb to room temperature water and soak. Soak chicken gizzard lining separately for 30 minutes, and soak the other herbs for 1 hour. After soaking, each herb, along with the soaking solution, will be sent to the subsequent extraction process of the corresponding group.

[0068] S4: Extraction and Concentration of Group A with Alcohol Precipitation. Dandelion, Corydalis, and corn silk were mixed as Group A. Water, equivalent to 8 times the total weight of the group's herbs, was added for each extraction, and the mixture was decocted three times, 0.5 hours each time. The extracts were filtered through a 100-mesh filter and the filtrates were combined. The solution was concentrated under reduced pressure at 60℃ and -0.06 MPa to a relative density of 1.12. The solution was transferred to an alcohol precipitation tank, stirred at 60 rpm, and 95 vol% ethanol was injected until the final concentration of 70 vol% was reached. The solution was refrigerated at 0℃ for 12 hours. The supernatant was collected, filtered, and after recovering the ethanol under reduced pressure, concentrated to a relative density of 1.15 to obtain concentrate A.

[0069] S5: Extraction and Concentration of Group B with Alcohol Precipitation. A mixture of Lysimachia christinae, Glycyrrhiza uralensis, and Plantago asiatica was used as Group B. Water, equivalent to eight times the total weight of the herbs in this group, was added and decocted twice, 0.5 hours each time. The filtrates were filtered and combined, then concentrated under reduced pressure at 60°C to a relative density of 1.09. Under vortex stirring and spraying conditions, 95 vol% ethanol was added until the final ethanol concentration reached 65 vol%. The mixture was refrigerated at 0°C for 12 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density determination, the relative density was adjusted to 1.15 by reduced pressure concentration or by adding purified water to obtain concentrate B.

[0070] S6: Extraction and Concentration of Group C by Alcohol Precipitation. Chicken gizzard lining was used as Group C. It was decocted four times with water (eight times its weight) for 0.5 hours each time. After filtration and combining the filtrates, the solution was concentrated under reduced pressure at 60°C. When the relative density reached 1.15, a forced circulation pump was started, controlling the flow rate in the tubing at 1.5 m / s, until the relative density reached 1.20. The solution was then transferred to an alcohol precipitation tank and injected with ethanol at 0.2 MPa to 75 vol% through a bottom Venturi jet injector. The mixture was refrigerated at 0°C for 12 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density measurement results, the solution was concentrated under reduced pressure or purified water was added to adjust the relative density to 1.15, yielding concentrate C.

[0071] S7: Extraction and Concentration of Group D with Alcohol Precipitation. A mixture of Lygodium japonicum and coarsely crushed Houttuynia cordata was used as Group D. Water, equivalent to 8 times the total weight of the herbs in this group, was added and decocted twice, 0.5 hours each time. The slurry was pumped into a plate and frame filter press, maintaining an initial pressure of 0.1 MPa for 10 minutes to form a 5 mm fiber filter aid layer in situ. The pressure was then increased to 0.2 MPa to complete filtration. The mixture was concentrated under reduced pressure at 60℃ to a relative density of 1.14. 95 vol% ethanol was added until the final ethanol concentration reached 60 vol%, and the mixture was refrigerated at 0℃ for 12 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density measurement results, the relative density was adjusted to 1.15 by reduced pressure concentration or by adding purified water to obtain concentrate D.

[0072] S8: Constant Temperature Preparation and Aseptic Filling. Combine all concentrates in a mixing tank, maintaining the temperature at 35°C. Add fructooligosaccharides, steviol glycosides, and sodium benzoate, stirring to dissolve. Then, bring the volume to 1000L with sterile purified water. Finally, pre-filter through a 0.45μm microporous membrane, followed by sterile fine filtration through a 0.22μm sterile-grade microporous membrane, and aseptically dispense in a Class 100 clean area.

[0073] Example 3:

[0074] This embodiment provides an oral liquid that facilitates the expulsion of stones and detoxification, and its preparation process, including the following steps:

[0075] S1: Weigh the raw materials by weight: 15kg chicken gizzard lining, 8kg dandelion, 6kg houttuynia cordata, 15kg lygodium japonicum, 7kg plantain, 15kg corn silk, 20kg lysimachia christinae, 10kg corydalis yanhusuo, 4kg licorice, and weigh out 3kg fructooligosaccharides, 0.1kg steviol glycosides, and 0.3kg sodium benzoate.

[0076] S2: Pre-treatment of Chinese medicinal materials. Chicken gizzard lining, dandelion, plantain, corn silk, lysimachia christinae, corydalis yanhusuo, and licorice are pulverized and passed through an 80-mesh sieve to obtain fine powder; Lygodium japonicum is not pulverized; Houttuynia cordata is coarsely pulverized and passed through a 10-mesh sieve, and the length D50 of the obtained plant fibers is controlled to be about 3mm, with the fiber length mainly distributed in the range of 2-4mm.

[0077] S3: Soaking the herbs. Soak each herb separately in room temperature water at 8 times its weight. Soak the chicken gizzard lining separately for 30 minutes, and soak the other herbs for 2 hours. After soaking, each herb, along with the soaking liquid, will be sent to the subsequent extraction process of the corresponding group.

[0078] S4: Extraction and Concentration of Group A (Alcohol Precipitation). Dandelion, Corydalis, and corn silk were mixed as Group A. Water, equivalent to 10 times the total weight of the group's herbs, was added for each extraction, and the mixture was decocted three times, 1 hour each time. The filtrates were filtered through a 200-mesh filter and combined. The filtrates were concentrated under reduced pressure at 70℃ and -0.08 MPa to a relative density of 1.14. The filtrate was transferred to an alcohol precipitation tank, stirred at 90 rpm, and 95 vol% ethanol was injected until the final concentration of 70 vol% was reached. The mixture was refrigerated at 4℃ for 24 hours. The supernatant was collected, filtered, and after recovering the ethanol under reduced pressure, concentrated to a relative density of 1.20 to obtain concentrate A.

[0079] S5: Extraction and Concentration of Group B with Alcohol Precipitation. A mixture of Lysimachia christinae, Glycyrrhiza uralensis, and Plantago asiatica was used as Group B. Water, equivalent to 10 times the total weight of the herbs in this group, was added and decocted twice, 1 hour each time. The filtrates were filtered and combined, then concentrated under reduced pressure at 70°C to a relative density of 1.11. Under vortex stirring and spraying conditions, 95 vol% ethanol was added until the final ethanol concentration reached 65 vol%. The mixture was refrigerated at 4°C for 24 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density determination, the relative density was adjusted to 1.20 by reduced pressure concentration or by adding purified water to obtain concentrate B.

[0080] S6: Extraction and Concentration of Group C (Alcohol Precipitation). Chicken gizzard lining was used as Group C. It was decocted four times with water (10 times its weight) for one hour each time. After filtration and combining the filtrates, it was concentrated under reduced pressure at 70°C. When the relative density reached 1.15, a forced circulation pump was started, controlling the flow rate in the tubing at 2.0 m / s, until the relative density reached 1.25. The solution was then transferred to an alcohol precipitation tank and injected with ethanol at 0.4 MPa to 75 vol% through a bottom Venturi jet injector. The mixture was refrigerated at 4°C for 24 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density measurement results, the relative density was adjusted to 1.20 by reduced pressure concentration or by adding purified water, yielding concentrate C.

[0081] S7: Extraction and Concentration of Group D with Alcohol Precipitation. A mixture of Lygodium japonicum and coarsely crushed Houttuynia cordata was used as Group D. Water equivalent to 10 times the total weight of the herbs in this group was added and decocted twice, 1 hour each time. The slurry was pumped into a plate and frame filter press, maintaining an initial pressure of 0.2 MPa for 15 minutes to form a 15 mm fiber filter aid layer in situ. The pressure was then increased to 0.3 MPa to complete filtration. The mixture was concentrated under reduced pressure at 70℃ to a relative density of 1.18. 95 vol% ethanol was added until the final ethanol concentration reached 60 vol%, and the mixture was refrigerated at 4℃ for 24 hours. The supernatant was collected, filtered, and the ethanol was recovered under reduced pressure. Based on the relative density measurement results, the relative density was adjusted to 1.20 by reduced pressure concentration or by adding purified water to obtain concentrate D.

[0082] S8: Constant Temperature Preparation and Aseptic Filling. Combine all concentrates in a mixing tank, maintaining the temperature at 40°C. Add fructooligosaccharides, steviol glycosides, and sodium benzoate, stirring to dissolve. Adjust the volume to 1000L with sterile purified water. Finally, pre-filter through a 0.45μm microporous membrane, followed by sterile fine filtration through a 0.22μm sterile-grade microporous membrane, and aseptically dispense in a Class 100 clean area.

[0083] Comparative Example 1:

[0084] Compared with Example 1, the difference is that in step S2, the houttuynia cordata is thoroughly crushed by a hammer mill and passed through a 70-mesh sieve to obtain fine powder, without retaining the long chain structure of plant fiber; in step S7, the same initial low pressure and subsequent pressure filtration parameters as in Example 1 are used for pressure filtration, but because the houttuynia cordata has been crushed into fine powder, the 10mm loose fiber filter aid layer described in Example 1 is not formed, and the rest are the same.

[0085] Comparative Example 2:

[0086] Compared with Example 1, the difference is that in step S6, after the chicken gizzard extract of Group C was concentrated under reduced pressure to a relative density of 1.15, the forced circulation pump was not turned on to control the flow rate of the tubing. Instead, the conventional static heating method was used to continue to concentrate under reduced pressure to a relative density of 1.22. All other steps are the same.

[0087] Comparative Example 3:

[0088] Compared with Example 1, the difference is that in step S6, after the high-density concentrated chicken gizzard lining of Group C is introduced into the alcohol precipitation tank, the venturi jet injector at the bottom is not used for high-pressure bottom feeding. Instead, the same atomized spraying above the liquid surface combined with vortex stirring method as Group A is used to add ethanol until the final concentration reaches 75 vol%. The rest are the same.

[0089] Comparative Example 4:

[0090] Compared with Example 1, the difference is that in step S8, the jacket cooling water was not turned on to keep the liquid preparation system constant at 37°C for cold preparation. Instead, 80°C high-temperature heating was used for liquid preparation and sugar dissolution. After volume adjustment, 0.45μm microporous membrane pre-filtration and 0.22μm sterilization-grade microporous membrane physical sterilization and fine filtration were not used. Instead, conventional 121°C high-temperature autoclaving sterilization was used for 30 minutes. All other aspects are the same.

[0091] Comparative Example 5:

[0092] Compared with Example 1, the difference lies in the following: the component separation and fluid control engineering design are completely broken. All the pretreated Chinese herbal raw materials are mixed together, and water equivalent to 9 times the total weight of all Chinese herbal raw materials is added each time. The mixture is decocted and extracted 3 times, each time for 0.8 hours. The mixed slurry after decoction is directly pumped into a plate and frame filter press, and the filtration pressure is controlled at 0.25 MPa to complete the full filtration. After the filtrates are combined, they are concentrated under reduced pressure at 65°C and a vacuum degree of -0.07 MPa to a relative density of 1.16. Then, they are transferred to an alcohol precipitation tank, and 95 vol% ethanol is added by atomizing the liquid surface under vortex stirring at 75 r / min, so that the final ethanol concentration of the system reaches 70 vol%. After refrigeration at 2°C for 18 hours, the supernatant is taken, filtered, and the ethanol is recovered under reduced pressure. According to the relative density measurement results, the relative density is adjusted to 1.18 by reduced pressure concentration or the addition of purified water to obtain a mixed concentrate. Finally, the solution is prepared by high-temperature sugar dissolution at 80°C and high-temperature autoclaving at 121°C for 30 minutes. The dosage of other ingredients is the same.

[0093] Test Example 1:

[0094] Experimental Description: This test aims to verify the filtration time and average membrane flux changes during the pressure filtration process, and to examine the physical filtration effect of the long-chain structure of plant fibers retained through a specific pulverization process in the solid-liquid separation system.

[0095] Experimental steps:

[0096] Take the extracts and dregs from Group D of Examples 1-3 and Comparative Example 1 after decoction and mix them with the dregs, respectively. Take the extracts and dregs from all Chinese herbal raw materials of Comparative Example 5 after decoction and mix them with the dregs. Adjust the total volume of the initial test slurry for each group to 50.0L.

[0097] Each of the above-mentioned mixed slurries was pumped into a pilot-scale plate and frame filter press with the same effective filtration area, which was set to 1.5 m². 2 .

[0098] Examples 1-3 and Comparative Example 1 were subjected to pressure filtration according to the initial low-pressure stratification and subsequent pressure-boosting filtration parameters recorded therein; Comparative Example 5 was subjected to full filtration at a constant filtration pressure of 0.25 MPa as recorded therein.

[0099] Record the total time (in minutes) from when the feed pump starts to when the filtrate discharge from the plate and frame filter press no longer flows out in a continuous linear stream.

[0100] All filtrates were collected and their actual volumes were recorded. To eliminate volume differences caused by varying filter cake holding capacities, the average membrane flux of each group was uniformly converted to the filtrate flux corresponding to processing 50.0 L of slurry. The average membrane flux (L / m²) of each group was calculated using filtrate volume, filtration area, and total processing time. 2 The average membrane flux J is calculated using the formula: J = V / (A × t), where V is the equivalent filtrate volume (50.0 L) in L; and A is the effective filtration area (m²). 2 t represents the total filtration time, in hours (h).

[0101] The experimental data are shown in Table 1:

[0102] Table 1: Test Data Results of Solid-Liquid Separation Flux and Filtration Efficiency

[0103] Example 1 36.5 54.8 Example 2 42.8 46.7 Example 3 38.1 52.5 Comparative Example 1 167.4 11.9 Comparative Example 5 182.9 10.9

[0104] According to the data in Table 1, under the same test slurry volume and the same effective filtration area, the total filtration time for Examples 1-3 was 36.5-42.8 min, and the average membrane flux was 46.7-54.8 L / m². 2 • h; The total filtration times for Comparative Examples 1 and 5 were 167.4 min and 182.9 min, respectively, with average membrane fluxes of 11.9 L / m³. 2 ·h and 10.9L / m 2 Under the test conditions, the average membrane flux of the example group was approximately 3.9-5.0 times that of the comparative group, indicating that the example scheme has high filtration efficiency in the solid-liquid separation process of the material in group D.

[0105] Analysis of the material composition and filtration process reveals that Lygodium japonicum, being a fine granular medicinal material, easily migrates to the filter cloth surface with the liquid phase in the water-extracted slurry. In Comparative Example 1, Houttuynia cordata was pulverized into a 70-mesh fine powder, lacking a supporting plant fiber structure in the system. During pressure filtration, the fine particles of Lygodium japonicum and some of the fine powder of the medicinal material tend to aggregate on the filter cloth surface, potentially increasing the density of the filter cake and raising the filtration resistance, thereby prolonging the filtration time and reducing the average membrane flux.

[0106] In Examples 1-3, the houttuynia cordata retains a certain length of plant fiber chains after coarse crushing. In the initial stage of pressure filtration, under lower filtration pressure, the plant fibers can interlock and accumulate on the filter cloth surface, which is beneficial for forming an initial fiber layer with a certain porous structure. This fiber layer can provide support and dispersion for the fine particles of Lygodium japonicum and the fine powder of the medicinal material, reducing the direct deposition of fine particles on the pore surface of the filter cloth.

[0107] In the subsequent pressurized filtration stage, the fine particles of Lygodium japonicum can be dispersed and retained in the fiber layer and the pores of the filter cake, making the filter cake structure relatively loose and conducive to maintaining the filtrate passage path. Therefore, the example group is superior to Comparative Example 1 and Comparative Example 5 in terms of filtration time and average membrane flux. The above results indicate that by controlling the coarseness of Houttuynia cordata and forming a fiber filter aid structure during the pressurized filtration process, the solid-liquid separation performance of the water-extracted slurry containing Lygodium japonicum can be improved to a certain extent, and the retention of extract in the process caused by prolonged filtration time can be reduced.

[0108] Test Example 2:

[0109] Experimental Description: This test aims to verify the coking condition of the tube wall and the degree of browning of the material during the concentration process, and to examine the impact of the forced circulation fluid control technology introduced in the high-density concentration process on the heat exchange interface state and the thermal stability of the material.

[0110] Experimental steps:

[0111] The filtrates from Group C or the mixed group after extraction in Examples 1-3, Comparative Examples 2 and 5 were used as test stock solutions.

[0112] Each group of test stock solutions was introduced into an externally heated vacuum concentrator equipped with a forced circulation system or a conventional static system, and concentrated under reduced pressure according to the temperature, vacuum degree and fluid control parameters set in each embodiment and comparative example until the set target relative density was reached.

[0113] After the concentration operation is completed, empty the material from the concentrator and rinse the equipment. Collect the material from a unit heating area of ​​0.5m² using a mechanical scraping method. 2 The carbonized scale adhering to the heat exchanger tube walls in the test area was dried to constant weight at 105℃, and the residual coking amount on the tube walls of each group was weighed and calculated in g / m. 2 .

[0114] Take equal volumes of the final concentrated solution samples from each group and dilute them 100 times with purified water. Place the diluted solution in a quartz cuvette and measure the absorbance of the system at a wavelength of 420 nm using a UV-Vis spectrophotometer. This value is used as the Maillard browning index.

[0115] The experimental data are shown in Table 2:

[0116] Table 2: Test results of anti-coking and anti-browning properties of high-density concentrate

[0117] Example 1 3.2 0.124 Example 2 2.8 0.131 Example 3 3.5 0.118 Comparative Example 2 87.6 0.765 Comparative Example 5 95.2 0.812

[0118] According to the data in Table 2, the residual coking on the pipe wall in Examples 1-3 ranged from 2.8 to 3.5 g / m. 2 The Maillard browning index ranged from 0.118 to 0.131. The residual coking on the pipe walls of Comparative Examples 2 and 5 were 87.6 g / m². 2 and 95.2g / m 2 The corresponding browning indices increased to 0.765 and 0.812. These results indicate that during the concentration process to achieve the target relative density, the amount of coking residue on the pipe wall and the browning index in the example group were both lower than those in the comparative group, suggesting that forced circulation fluid control conditions have a certain improving effect on reducing wall adhesion residue and browning degree during the concentration process.

[0119] Although Comparative Example 5 had a final relative density of 1.16, lower than Group C in Example 1 (1.22), it employed a combined extraction and concentration method for all medicinal materials, potentially resulting in the simultaneous presence of polysaccharides, proteins, peptides, mucilage, and fine powders in the system. This complex composition may increase the viscosity and wall-adhering deposition tendency of the concentrate; furthermore, the lower solid-liquid separation efficiency in the initial stage may prolong the heating time of the materials in subsequent processes. Therefore, Comparative Example 5 still exhibited a higher residual coking content on the pipe wall and a higher browning index.

[0120] Analysis of the material properties shows that the chicken gizzard extract contains a certain amount of peptides, amino acids, and other components. As the concentration process progresses, the relative density of the concentrate increases, and the viscosity of the system usually increases as well. The flow rate of the material near the heat exchanger tube wall may decrease. Under the conventional static vacuum concentration conditions of Comparative Example 2, higher viscosity materials are more likely to form stagnant areas near the heating interface, thereby increasing the possibility of uneven local heating and residue adhering to the wall.

[0121] Under prolonged localized heating, components such as amino acids and sugars in the concentrate may undergo browning reactions, manifested as an increase in absorbance at 420 nm in the diluted solution. Simultaneously, materials adhering to the heat exchanger tube wall may form solidified residues due to continuous heating, further increasing the amount of coking residue on the tube wall. Therefore, the amount of coking residue on the tube wall and the absorbance at 420 nm can serve as reference indicators for evaluating the thermal stability of the concentration process and the extent of wall adhesion residue.

[0122] In Examples 1-3, the forced circulation pump was started after the relative density of the concentrate reached a set critical value, and the tube-side flow rate was controlled within the range of 1.5-2.0 m / s. This fluid control method can increase the flow renewal frequency of the concentrate in the heat exchange tube section, which helps to reduce the long-term residence of material near the tube wall and improve the heat transfer uniformity near the heat exchange interface. Although the concentration temperature and final relative density of Example 3 were relatively high, its tube-side flow rate was simultaneously increased to 2.0 m / s. In this test, no higher browning index was observed, indicating that increasing the tube-side flow rate may have a certain compensatory effect on browning control during the high-density concentration stage.

[0123] In summary, the forced circulation concentration process used in the embodiments can improve the material flow state during the high-density concentration stage, reduce coking residue on the heat exchange tube wall and the degree of browning of the material, thereby improving the process stability of the concentration process.

[0124] Test Example 3:

[0125] Experimental Description: This test aims to verify the effects of different fluid injection and mixing methods on the precipitation morphology of macromolecules and the transfer and retention of small molecule target components when high-concentration ethanol is added to high-density water extract.

[0126] Experimental steps:

[0127] The concentrated ethanol precipitation solution of Group C in Examples 1-3 and Comparative Example 3, as well as the concentrated ethanol precipitation solution of all medicinal materials in Comparative Example 5, were collected as test samples.

[0128] Accurately measure the initial volume of each group of alcohol precipitation solutions, take samples and determine the total free amino acid concentration in the system using the ninhydrin colorimetric method, and calculate the absolute mass of total free amino acids in each group before alcohol precipitation.

[0129] The ethanol addition operation was carried out according to the high-pressure bottom feeding injection or liquid surface spraying method and target concentration described in each embodiment and comparative example. At the end of the ethanol addition process, a suspension sample was taken from the mixed system and placed in a laser particle size analyzer to determine the median diameter volume distribution value, i.e., D50, of the precipitated protein flocs.

[0130] Each group of materials was allowed to stand and separate under set low temperature conditions, and all supernatant liquid phases were collected.

[0131] Remove the ethanol solvent from the supernatant under reduced pressure, adjust and record the volume of the aqueous phase. Take a sample again to determine the concentration of total free amino acids in the system, and calculate the absolute mass of total free amino acids in the supernatant after alcohol precipitation.

[0132] The total free amino acid retention rate of each group was obtained by dividing the absolute mass of the total free amino acids in the supernatant after alcohol precipitation by the initial absolute mass before alcohol precipitation.

[0133] The experimental data are shown in Table 3:

[0134] Table 3: Test results of phase change and anti-encapsulation retention rate of materials during alcohol precipitation.

[0135] Example 1 45.2 88.4 Example 2 48.7 86.1 Example 3 41.5 89.7 Comparative Example 3 312.4 65.2 Comparative Example 5 348.1 59.8

[0136] According to the data in Table 3, under the test conditions, the median diameter (D50) of the protein precipitates in Examples 1-3 was 41.5-48.7 μm, and the total free amino acid retention rate was 86.1%-89.7%. The median diameter (D50) of the protein precipitates in Comparative Examples 3 and 5 were 312.4 μm and 348.1 μm, respectively, and the total free amino acid retention rates were 65.2% and 59.8%, respectively. These results indicate that during the high-density water extract alcohol precipitation process, the precipitate flocs formed in the Example group had relatively smaller particle sizes, and the total free amino acid retention rate in the supernatant was higher than that in the Comparative Example group. This suggests that the bottom jet alcohol injection method has a certain improving effect on the control of precipitate floc particle size and the retention of small molecule components.

[0137] Analysis of the alcohol precipitation process reveals that high-density aqueous extracts typically contain macromolecular components such as proteins and peptides. The addition of high-concentration ethanol alters the system's polarity and hydration environment, potentially causing these macromolecular components to precipitate and form flocculent precipitates. In Comparative Examples 3 and 5, ethanol was added via a mist spray method above the liquid surface. Given the high viscosity of the high-density extract, the diffusion of ethanol into the extract and the uniformity of mixing may be limited, leading to a rapid increase in ethanol concentration in localized areas. This can easily promote the rapid aggregation of macromolecular components in these localized areas, forming large-particle-size flocculent structures.

[0138] During the formation and sedimentation of larger-diameter flocs, some small-molecule components such as free amino acids that have not yet been fully transferred to the continuous liquid phase may be entrained or embedded, causing these small molecules to separate along with the precipitate. Therefore, there is a certain correlation between the larger D50 values ​​and the lower total free amino acid retention rates in Comparative Examples 3 and 5.

[0139] Examples 1-3 employed a bottom Venturi jet injector to inject ethanol. After entering the high-density aqueous extract from the bottom, the ethanol, under the action of the jet, forms a strong local mixing and shearing effect with the feed solution, which helps to improve the dispersion of ethanol in the feed solution and reduce local ethanol concentration differences. Under these conditions, the precipitation process of macromolecular components such as proteins is relatively dispersed, resulting in smaller precipitate flocs.

[0140] Smaller-sized discrete precipitates typically exhibit a lower tendency to encapsulate large-scale particles, and when the ethanol and aqueous phase are mixed relatively uniformly, small molecule components such as free amino acids have ample space for diffusion and transfer. Therefore, the example group retained a higher proportion of total free amino acids in the supernatant after ethanol precipitation.

[0141] In summary, the results show that using bottom jet ethanol injection during the alcohol precipitation stage of the high-density concentrate in Group C can improve the mixing uniformity during the ethanol addition process to a certain extent, reduce the formation of large-particle flocs and their risk of entrainment of small-molecule components, thereby helping to improve the retention rate of total free amino acids in the supernatant after alcohol precipitation.

[0142] Test Example 4:

[0143] Experimental Description: This test aims to verify the degree of damage to the structure of heat-sensitive prebiotics caused by different temperatures and process conditions during the solution preparation and sterilization stages, and to examine the effect of process parameter adjustments on the concentration distribution of the target fructooligosaccharide and its thermal degradation products in the finished formulation.

[0144] Experimental steps:

[0145] The finished oral liquids obtained from Examples 1-3, Comparative Example 4, and Comparative Example 5 after the final filling process were collected as test samples.

[0146] Accurately pipette 2.0 mL of each test sample into a centrifuge tube, centrifuge at 10000 r / min for 15 min, take the supernatant and filter it through a 0.45 μm microporous membrane, and use the resulting filtrate as the test solution.

[0147] Weigh out oligofructose reference standards with a degree of polymerization between 3 and 5, as well as low molecular weight monosaccharides and disaccharides such as fructose, glucose, and sucrose, dissolve and dilute them in water to prepare a mixed reference solution containing the target polysaccharide and degraded monosaccharides and disaccharides.

[0148] The determination was performed using a high-performance liquid chromatograph equipped with a differential refractive index detector. The chromatographic conditions were set as follows: amino column, mobile phase of acetonitrile and water (70:30 v / v), flow rate of 1.0 mL / min, and column and detector temperatures maintained at 35 °C.

[0149] Inject the reference solution and the test solution separately into the liquid chromatograph and record the chromatograms and peak areas. Calculate the mass concentration of effective fructooligosaccharides and the mass concentration of low molecular weight monosaccharides and disaccharides in each group of test solutions using the external standard curve.

[0150] The experimental data are shown in Table 4:

[0151] Table 4: Results of Test Data on Structural Integrity Analysis of Thermosensitive Prebiotics

[0152] Example 1 2.87 0.35 Example 2 2.94 0.32 Example 3 2.82 0.38 Comparative Example 4 1.15 1.98 Comparative Example 5 0.89 2.31

[0153] according to Figure 1Based on the data in Table 4, under the test conditions, the effective fructooligosaccharide concentration in Examples 1-3 was 2.82-2.94 mg / mL, and the concentration of low molecular weight monosaccharides and disaccharides was 0.32-0.38 mg / mL; the effective fructooligosaccharide concentrations in Comparative Examples 4 and 5 were 1.15 mg / mL and 0.89 mg / mL, respectively, and the concentrations of low molecular weight monosaccharides and disaccharides were 1.98 mg / mL and 2.31 mg / mL, respectively. These results indicate that the retention level of effective fructooligosaccharides in the Example groups was higher than that in the Comparative Examples, while the content of low molecular weight monosaccharides and disaccharides was lower than that in the Comparative Examples, suggesting that the temperature conditions and sterilization methods during solution preparation and sterilization have a certain impact on the structural integrity of fructooligosaccharides.

[0154] Analysis of the structural characteristics of fructooligosaccharides (FOS) reveals that they are primarily formed by fructose groups linked by β2-1 glycosidic bonds. In aqueous systems, higher temperatures and longer heating times may increase the risk of glycosidic bond hydrolysis, especially under conditions where the aqueous extract of traditional Chinese medicine may be weakly acidic, where this effect is more pronounced. Comparative Examples 4 and 5 underwent high-temperature saccharification at 80℃ and autoclaving at 121℃ during the solution preparation or final treatment stages. The finished medicinal solutions experienced a high-temperature heat treatment process, resulting in a decrease in the effective concentration of fructooligosaccharides and an increase in the concentration of low-molecular-weight monosaccharides and disaccharides.

[0155] In Examples 1-3, the system temperature was controlled within the range of 35-40℃ during the concentrate mixing and preparation stage, and terminal sterilization was performed by pre-filtration using a 0.45μm microporous membrane combined with fine filtration using a 0.22μm sterilization-grade microporous membrane. This treatment method avoids the finished drug solution undergoing high-temperature autoclaving sterilization at the final stage, which helps reduce the thermal degradation of fructooligosaccharides during solution preparation and sterilization.

[0156] As shown in Table 4, the concentration of low molecular weight monosaccharides and disaccharides in the comparative group was significantly higher than that in the example group. This result corresponds to the decreasing trend of effective fructooligosaccharide concentration, suggesting that some fructooligosaccharides may undergo hydrolysis or structural transformation under high-temperature treatment conditions. In contrast, the effective fructooligosaccharide concentration in the example group remained at a higher level, while the concentration of low molecular weight monosaccharides and disaccharides was in a lower range, indicating that the low-temperature formulation combined with physical sterilization and fine filtration process can better maintain the stability of the target fructooligosaccharide components.

[0157] In summary, the results show that the constant temperature preparation at 35-40℃ and the pre-filtration at 0.45μm and sterilization filtration at 0.22μm used in the examples can reduce the impact of heat treatment on the structural integrity of fructooligosaccharides to a certain extent, and help maintain the target concentration of effective fructooligosaccharides in the finished oral liquid.

[0158] Test Example 5:

[0159] Experimental Description: This test aims to verify the in vitro proliferation-promoting effect of the finished oral liquid on specific oxalate-degrading strains in the human intestine, and to examine the differences in efficacy of different prepared liquids in retaining prebiotic functions and clearing stone precursors, namely free oxalate.

[0160] Experimental steps:

[0161] Standard commercial strains of formic acid-producing oxalobacterium were selected, activated under anaerobic conditions, and prepared into a basic bacterial suspension of standard concentration as the experimental test strain.

[0162] Prepare a liquid culture medium containing basic nutrients, and add sodium oxalate at an initial concentration of 10.0 mmol / L as the initial carbon source and degradation substrate.

[0163] A blank control group, an example group, and a comparative group were established. For the blank control group, an appropriate amount of sterile purified water was added to the culture medium. For the example group and the comparative group, equal amounts of the final oral liquid products from Examples 1-3 and Comparative Examples 4 and 5 were added to the culture medium. The amount of drug solution added to each group was controlled at 1 vol% of the culture medium volume, and the initial pH of each group's culture medium was adjusted to the range of 6.8-7.0. A background blank group was also established, but without inoculation, with the same amount of the corresponding drug solution added to eliminate the influence of the drug solution's color and turbidity on the OD600 measurement results. Simultaneously, a sodium benzoate control group corresponding to the final concentration of sodium benzoate in each sample was set up to eliminate the interference of preservative differences on bacterial proliferation.

[0164] Each group was inoculated with the same volume of basic bacterial suspension and placed in an anaerobic incubator at 37°C for continuous static incubation for 48 hours.

[0165] After the culture was completed, the absorbance value (OD600) of each group of culture solution was measured at a wavelength of 600 nm. After subtracting the OD600 value of the corresponding uninoculated background blank group, the result was used to evaluate the proliferation density of the corresponding bacterial cells.

[0166] Centrifuge each group of culture media, take the supernatant and use high performance liquid chromatography to determine the residual concentration of oxalate in it, and calculate the oxalate degradation rate of each group in combination with the initial addition amount.

[0167] The experimental data are shown in Table 5:

[0168] Table 5: Results of Proliferation and Activity Tests of Targeted Oxalic Acid Degrading Strains

[0169] Blank control group 0.42 12.4 Example 1 1.84 87.2 Example 2 1.76 84.5 Example 3 1.91 89.3 Comparative Example 4 0.65 25.6 Comparative Example 5 0.58 22.1

[0170] according to Figure 2According to the data in Table 5, under the test conditions, the OD600 of the culture medium after background subtraction in the blank control group was 0.42, and the oxalate degradation rate was 12.4%; the OD600 of the culture medium after background subtraction in Examples 1-3 was 1.76-1.91, and the oxalate degradation rate was 84.5%-89.3%; the OD600 of the culture medium after background subtraction in Comparative Examples 4 and 5 were 0.65 and 0.58, respectively, and the oxalate degradation rates were 25.6% and 22.1%, respectively. These results indicate that in the in vitro anaerobic culture system containing 10.0 mmol / L sodium oxalate, the bacterial proliferation level and oxalate degradation rate of the Example groups were higher than those of the blank control group and the Comparative Example groups.

[0171] *Formic acid-producing oxalobacterium* is an anaerobic strain involved in oxalate metabolism. In this test system, sodium oxalate was present as the main metabolic substrate. OD600 was used to evaluate the bacterial proliferation level after culture, and oxalate degradation rate was used to evaluate the reduction of oxalate in the culture system. The OD600 and oxalate degradation rate of the example group were both at high levels, indicating that the finished oral liquid of the example group has a certain supporting effect on the proliferation status and oxalate degradation activity of this strain in the in vitro system.

[0172] Based on the results of Test Example 4 above, Examples 1-3, using a constant temperature of 35-40℃ and a 0.45μm pre-filtration and 0.22μm sterile fine filtration process, maintained a high concentration of effective fructooligosaccharides and a low content of low molecular weight monosaccharides and disaccharides in the finished product. Therefore, the performance of the Example group in Test Example 5 may be related to its retention of a high level of fructooligosaccharide components and some heat-sensitive small molecule components. These components may have a certain impact on bacterial survival, proliferation, or metabolic environment in the culture system, resulting in an increase in OD600 and an improved oxalate degradation rate.

[0173] Comparative Examples 4 and 5 underwent high-temperature sugar conversion at 80°C and autoclaving at 121°C during solution preparation or final processing. Combined with the results of Test Example 4, the content of effective fructooligosaccharides decreased and the content of low-molecular-weight monosaccharides and disaccharides increased in the comparative examples. This change suggests that high-temperature treatment may alter the composition of prebiotics and related heat-sensitive components in the finished drug solution, weakening their support for the *Oxalis formic acid-producing* culture system. Therefore, although the comparative examples showed some improvement compared to the blank control group, their OD600 and oxalate degradation rate were significantly lower than those of the example group.

[0174] It should be noted that this test is an in vitro culture experiment, and its results are mainly used to evaluate the effects of different preparation processes on the culture status and oxalate degradation ability of specific oxalate-degrading strains. The test results, from an in vitro perspective, indicate that the process described in the example is beneficial in maintaining the functional components in the finished product that are related to the strain's culture environment, and exhibits better cell proliferation and oxalate degradation effects in oxalate-containing culture systems.

[0175] 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. An oral liquid that facilitates the expulsion of stones and detoxification, characterized in that, Made from the following ingredients in parts by weight: Chicken gizzard lining 10-15 parts; 6-8 portions of dandelion; 5-6 parts of houttuynia cordata; 10-15 servings of sea ginseng; 5-7 parts plantain; 10-15 parts corn silk; 15-20 parts of moneywort; 8-10 parts of Corydalis Rhizome; Licorice 2-4 parts; 2-4 parts of fructooligosaccharides; Stevioside 0.05-0.1 parts; Sodium benzoate 0.1-0.3 parts.

2. The oral liquid according to claim 1, which facilitates the expulsion of stones and detoxification, is characterized in that... The fructooligosaccharide is a fructooligosaccharide with a degree of polymerization of 3 to 5 and containing β2-1 glycosidic bonds; in the oral liquid, the mass concentration of fructooligosaccharide is 2.82-2.94 mg / mL, and the mass concentration of low molecular weight monosaccharides and disaccharides is 0.32-0.38 mg / mL.

3. The oral liquid according to claim 1, which facilitates the expulsion of stones and detoxification, is characterized in that... The oral liquid is prepared by sterilization filtration using a microporous membrane with a pore size of 0.22 μm.

4. A preparation process for an oral liquid that facilitates stone expulsion and detoxification as described in any one of claims 1-3, characterized in that, Includes the following steps: S1: Weigh the raw materials by weight: 10-15 parts chicken gizzard lining, 6-8 parts dandelion, 5-6 parts houttuynia cordata, 10-15 parts lygodium japonicum, 5-7 parts plantain, 10-15 parts corn silk, 15-20 parts lysimachia christinae, 8-10 parts corydalis yanhusuo, 2-4 parts licorice, 2-4 parts fructooligosaccharides, 0.05-0.1 parts steviol glycoside, and 0.1-0.3 parts sodium benzoate; S2: Chicken gizzard lining, dandelion, plantain, corn silk, lysimachia christinae, corydalis, and licorice are pulverized; houttuynia cordata is coarsely pulverized to control the plant fiber length distribution within the range of 0.5-4mm; lygodium japonicum is left untreated. S3: Soak the raw materials processed in step S2 in room temperature water; S4: Dandelion, Corydalis and corn silk were mixed as group A, water was added and decocted for extraction, the filtrates were filtered and combined, concentrated under reduced pressure, vortexed and ethanol was sprayed on the liquid surface for alcohol precipitation, refrigerated, the supernatant was taken to recover the ethanol and concentrated to obtain concentrate A. S5: Mix Lysimachia christinae, Glycyrrhiza uralensis and Plantago asiatica as Group B, add water to decoct and extract, filter and combine the filtrates, concentrate under reduced pressure, perform vortex stirring and spray ethanol above the liquid surface for alcohol precipitation, refrigerate, take the supernatant to recover ethanol and concentrate to obtain concentrate B. S6: Chicken gizzard lining was treated as a separate group C. It was boiled in water for extraction, filtered and combined. The filtrates were concentrated under reduced pressure using an externally heated vacuum concentrator with a forced circulation pump. The concentrated material was then introduced into an alcohol precipitation tank. Ethanol was injected from bottom to top through a Venturi jet injector at the bottom. The tank was refrigerated, and the supernatant was collected to recover the ethanol and concentrate it to obtain concentrate C. S7: Mix Lygodium japonicum with coarsely crushed Houttuynia cordata as Group D, add water and decoct to extract; pump the slurry of the extract and the residue into a plate and frame filter press, use the first pressure for initial filtration, form a plant fiber filter aid layer on the surface of the filter cloth, then increase the pressure to a second pressure higher than the first pressure to complete the filtration, and combine the filtrates; concentrate the filtrate under reduced pressure, spray ethanol above the liquid surface for alcohol precipitation, refrigerate, take the supernatant to recover the ethanol and concentrate to obtain concentrate D; S8: Combine the obtained concentrates A, B, C, and D into a mixing tank, maintain the temperature in the mixing tank at 35-40℃, add fructooligosaccharides, steviol glycosides, and sodium benzoate to dissolve, and add purified water to make up the volume; pre-filter the drug solution through a microporous membrane with a pore size of 0.45μm, and then finely filter it through a microporous membrane with a pore size of 0.22μm, and dispense the finished product.

5. The preparation process of the oral liquid that facilitates stone expulsion and detoxification according to claim 4, characterized in that, In step S6, the process of vacuum concentration using an externally heated vacuum concentrator with a forced circulation pump is as follows: the extract is concentrated under reduced pressure at 60-70℃. When the relative density reaches 1.15, the forced circulation pump is turned on and the flow rate in the tube is controlled at 1.5-2.0 m / s until the relative density reaches 1.20-1.25 and then the concentration is stopped. In step S6, the process of injecting ethanol from bottom to top through the venturi jet at the bottom is as follows: 95% ethanol is injected into the bottom of the alcohol precipitation tank at a pressure of 0.2-0.4 MPa through the venturi jet until the final ethanol volume concentration of the system reaches 75%.

6. The preparation process of the oral liquid that facilitates stone expulsion and detoxification according to claim 4, characterized in that, In step S7, the first pressure is 0.1-0.2 MPa, the initial pressure filtration time is 10-15 min, the thickness of the plant fiber filter aid layer is 5-15 mm, and the second pressure is 0.2-0.3 MPa.

7. The preparation process of the oral liquid that facilitates stone expulsion and detoxification according to claim 4, characterized in that, In step S2, the houttuynia cordata is coarsely crushed and passed through a 10-20 mesh sieve, and the median diameter D50 of the resulting plant fiber length is 1-3 mm; chicken gizzard lining, dandelion, plantain, corn silk, lysimachia christinae, corydalis yanhusuo, and licorice are pulverized and passed through a 60-80 mesh sieve.

8. The preparation process of the oral liquid that facilitates stone expulsion and detoxification according to claim 4, characterized in that, In steps S4 and S5, the temperature for vacuum concentration is 60-70℃; the process of spraying ethanol above the liquid surface for alcohol precipitation is as follows: 95% ethanol is added through an atomizing nozzle under vortex stirring at a speed of 60-90 r / min. In step S4, the final ethanol volume concentration of group A in the alcohol precipitation treatment is 70%; In step S5, the final ethanol volume concentration of group B in the alcohol precipitation treatment is 65%; In steps S4 and S5, the refrigeration temperature is 0-4℃ and the refrigeration time is 12-24h.

9. The preparation process of the oral liquid that facilitates stone expulsion and detoxification according to claim 4, characterized in that, In step S3, the raw materials processed in step S2 are soaked in room temperature water at 5-8 times their weight; chicken gizzard lining is soaked separately for 30 minutes, while dandelion, houttuynia cordata, lygodium japonicum, plantain, corn silk, lysimachia christinae, corydalis yanhusuo, and licorice are soaked for 1-2 hours.

10. The preparation process of the oral liquid that facilitates stone expulsion and detoxification according to claim 4, characterized in that, In step S4, add 8-10 times the weight of group A water and decoct 3 times, with each extraction lasting 0.5-1 hour. In step S5, add 8-10 times the weight of group B water and decoct twice, with each extraction lasting 0.5-1 hour. In step S6, add 8-10 times the weight of water from group C and decoct and extract 4 times, with each extraction lasting 0.5-1 hour. In step S7, add 8-10 times the weight of group D of water and decoct twice, with each extraction lasting 0.5-1 hour.

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