Herbal plant composition with the effect of nourishing yin and blood and application thereof

Abstract

The application relates to the technical field of traditional Chinese medicine and health food preparation, and discloses a herbal plant composition with the effects of nourishing yin and blood and application thereof, which is prepared from the following raw materials: angelica sinensis, safflower, rehmannia glutinosa, medlar, donkey-hide gelatin powder, fish collagen peptide, oligoisomaltose solution and konjac flour 5-15 parts; a preparation method thereof comprises the following steps: respectively preparing volatile phase A phase, polyphenol phase B phase and protein phase C1 liquid, mixing oligoisomaltose solution and konjac flour to obtain C2 liquid, adding C1 liquid to adjust pH and perform negative pressure evaporation to obtain C phase, pumping B phase into C phase to perform in-situ titration, so that the pH is stabilized at 3.8-4.0, the temperature is lowered to 35-40 DEG C, A phase is pumped in and uniformly mixed, degassing, sterile filling and then the finished product is obtained. The technical scheme that oligoisomaltose solution and konjac flour are used to construct a polysaccharide matrix and are matched with protein molecular weight ladder distribution is adopted, so that the technical effect that a steric hindrance hydration layer is formed inside the system and polyphenols and macromolecules are physically isolated is achieved.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine and health food preparation technology, specifically to herbal plant compositions with yin-nourishing and blood-tonifying effects and their applications. Background Technology

[0002] In modern life, due to long-term sleep deprivation and irregular eating habits, symptoms of qi and blood deficiency and yin deficiency are very common. Daily conditioning often requires the intake of health foods or traditional Chinese medicine preparations with yin-nourishing and blood-tonifying effects. Compared to traditional oral solid pills, liquid or semi-solid dosage forms are easier to swallow and have a faster onset of action, making them more popular in the market.

[0003] Existing liquid oral products for nourishing Yin and blood are typically prepared using water extraction and high-temperature blending methods. Manufacturers decoct various Chinese herbal medicine slices and filter the extract. Then, they directly add animal gelatin blocks, such as donkey-hide gelatin, to the hot decoction and stir until melted. Finally, they add conventional thickeners and fill the packaging. This conventional production process is very short and relatively simple. Pharmaceutical companies do not need to purchase special microfluidic control equipment or homogenization systems, greatly saving on initial fixed asset investment in the production line. At the same time, direct high-temperature decoction can simultaneously achieve commercial sterilization while accelerating material dissolution, resulting in high overall efficiency for large-scale production.

[0004] The aforementioned direct extraction and blending method has significant microscopic defects at the physicochemical level. The concentrated extracts of Rehmannia glutinosa and mulberry contain large amounts of plant polyphenols and tannins. Donkey-hide gelatin proteins contain proline-rich structural domains. When these two substances meet in an aqueous phase, the hydroxyl groups of the polyphenols immediately form strong hydrogen bonds and hydrophobic interactions with the amide groups of the proteins. The protein molecules then undergo irreversible cross-linking and flocculation, resulting in dark brown turbidity and precipitation after the product is bottled and left to stand for a period of time. Simultaneously, plant extracts are typically naturally acidic; direct pouring and mixing causes a rapid spike in the local hydrogen ion concentration. When the local pH rapidly approaches the protein's natural isoelectric point, the electrostatic repulsion on the protein particle surface disappears, and the protein conformation collapses directly due to acid stress. Furthermore, conventional liquid systems lack the support of a three-dimensional rheological network and cannot withstand the long-term effects of gravity. The active ingredients are highly prone to settling and stratifying during the shelf life. The dosage for a single patient dose cannot be guaranteed to be uniform. Once these clumps of complexes enter the digestive tract, gastrointestinal degrading enzymes have difficulty penetrating them, ultimately leading to a significant decrease in the bioavailability of these nourishing active substances. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a herbal plant composition with yin-nourishing and blood-tonifying effects and its application. This invention solves the problem in existing technologies where animal-derived proteins are directly compounded with Chinese medicinal materials rich in plant polyphenols and tannins into liquid or semi-solid dosage forms, resulting in irreversible cross-linking of polyphenol hydroxyl groups with protein amide groups, leading to flocculation and precipitation, local acid shock phase separation, and a significant reduction in the bioavailability of active ingredients.

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

[0007] In a first aspect, the present invention provides a herbal plant composition with the effects of nourishing yin and blood, using the following technical solution:

[0008] A herbal composition with yin-nourishing and blood-tonifying effects is made from the following raw materials in parts by weight: 200-300 parts Angelica sinensis; 10-50 parts Saffron; 500-1200 parts Rehmannia glutinosa; 400-800 parts Mulberry; 400-1000 parts Lycium barbarum; 100-400 parts Donkey-hide gelatin powder; 200-600 parts Fish collagen peptide; 4000-6000 parts Isomaltooligosaccharide solution; and 5-15 parts Konjac powder.

[0009] By employing the above technical solution, and using a specific ratio of isomaltooligosaccharide solution and konjac powder as the matrix, combined with the molecular weight gradient distribution of donkey-hide gelatin powder and fish collagen peptides, a steric hindrance hydration layer capable of physically isolating polyphenols and proteins is constructed within the system. Therefore, the effect of blocking macromolecular complexation precipitation and maintaining the uniformity and stability of the system is achieved. The specific reaction process by which this composition achieves microscopic anti-complexation is as follows:

[0010] In the initial stage of system hydration, fish collagen peptides, due to their low molecular weight and high proportion of glycine residues, will first bind with water molecules to form a continuous phase; at this time, the large collagen molecules in the donkey-hide gelatin powder will unfold their peptide chain structure in the aqueous phase, exposing the proline- and hydroxyproline-rich regions inside.

[0011] During this hydration process, the branched oligosaccharides with α-1,6 glycosidic bonds in the isomaltooligosaccharide solution establish a hydrogen bond network with water molecules and free polar groups through their hydroxyl groups. Simultaneously, the konjac glucomannan macromolecules released from the swelling of konjac powder interpenetrate into this oligosaccharide network, forming a supporting polymer backbone. This synergistic effect of macromolecular polysaccharides and branched oligosaccharides directly coats the unfolded donkey-hide gelatin protein chains, forming a dense hydration layer and producing a significant steric hindrance effect.

[0012] When plant polyphenols and tannins containing ingredients such as Rehmannia glutinosa and mulberry enter this system, the polyphenol molecules cannot penetrate the hydration layer to contact the proline residues on the main chain of donkey-hide gelatin because the hydrodynamic radius of the polyphenol molecules is larger than the micropore diameter of the dense hydration layer, and the physical repulsion generated by the konjac glucomannan backbone prevents them from doing so. This physical isolation completely severs the cross-linking reaction pathway between the polyphenol hydroxyl groups and the protein amide groups, thus avoiding the formation of insoluble complexes.

[0013] Ultimately, the dispersed phase composed of oligosaccharides and high-molecular-weight polysaccharides within the system, relying on intermolecular non-covalent cross-linking, endows the composition with pseudoplastic fluid characteristics. Its inherent initial yield stress is sufficient to overcome the effect of gravity, suspending and fixing incompletely dissolved particles and macromolecules, thereby preventing physical stratification under long-term static conditions.

[0014] Preferably, the raw materials are in the following weight proportions: 200 parts Angelica sinensis, 20 parts saffron, 800 parts Rehmannia glutinosa, 600 parts mulberry, 700 parts wolfberry, 250 parts donkey-hide gelatin powder, 400 parts fish collagen peptide, 5000 parts isomaltooligosaccharide solution, and 10 parts konjac powder.

[0015] By adopting the above technical solution, the number of oligosaccharide branches provided in the system is stoichiometrically matched with the number of protein amide groups, and the thickness and density of the hydration layer are balanced. This achieves complete spatial isolation of plant polyphenols and avoids the sharp increase in system viscosity and local gelation dehydration condensation reaction caused by excessive polysaccharide concentration.

[0016] Preferably, the main chain of the donkey-hide gelatin powder contains proline and hydroxyproline domains, wherein the L-hydroxyproline content is not less than 5%, the natural isoelectric point pH is 4.8, and the weight-average molecular weight distribution ranges from 20,000 Da to 80,000 Da; the average molecular weight of the fish collagen peptide is between 500 Da and 1,500 Da, and glycine residues account for one-third of the total amino acid residues in the peptide chain structure.

[0017] By employing the above technical solution, the macromolecules of donkey-hide gelatin and fish collagen peptides form a broad molecular weight distribution gradient ranging from 500 Da to 80,000 Da. Fish collagen peptides, as small molecule fillers, can embed themselves in the gaps between the macromolecules of donkey-hide gelatin, increasing the density of the protein phase. The specific range of L-hydroxyproline in the donkey-hide gelatin powder provides a large number of hydrogen bond donors that can bind to the hydroxyl groups of the polysaccharides, ensuring that the polysaccharide molecules can be firmly anchored to the protein chain surface; while the isoelectric point of 4.8 allows the system to maintain a certain electrostatic repulsion even in a slightly acidic environment, preserving the colloidal dispersion.

[0018] Preferably, the total dry matter mass fraction of the isomaltooligosaccharide solution is greater than or equal to 70%, wherein the oligosaccharides composed of isomaltooligosaccharide, panose, and isomaltooligosaccharide with a degree of polymerization of 2 to 10 account for more than 50% of the total dry matter mass; the main effective component of the konjac powder is konjac glucomannan, and the apparent viscosity of a 1% mass concentration aqueous solution at 25°C is 10000 mPa·s to 25000 mPa·s.

[0019] By employing the above technical solution, the branched oligosaccharide chains with a degree of polymerization between 2 and 10 have a moderate length, allowing them to freely penetrate into the spatial conformation of proteins to expel free water and reduce the water activity of the system; konjac glucomannan provides a large-scale network support framework. The combination of the two ensures that the macroscopic apparent viscosity is within a range suitable for liquid or semi-solid processing flow, while at the microscopic level it has sufficient mechanical strength to resist the penetration of polyphenol molecules.

[0020] Preferably, the raw material further includes a pH adjuster, which is one or a combination of potassium citrate and citric acid.

[0021] By adopting the above technical solution, a buffer system composed of potassium citrate and citric acid is introduced, which can precisely control and stabilize the hydrogen ion concentration of the system, make the pH value of the overall environment far away from the isoelectric point of proteins, increase the number of like charges on the surface of colloidal particles, and improve the anti-flocculation ability of the system by utilizing the electrostatic repulsion force of the double layer.

[0022] Secondly, the present invention provides a method for preparing a herbal plant composition with yin-nourishing and blood-tonifying effects, using the following technical solution:

[0023] A method for preparing a herbal plant composition with yin-nourishing and blood-tonifying effects includes the following steps:

[0024] S1. Provide, in proportion, an A-phase extract containing a volatile phase and a thermosensitive phase, a B-phase concentrate containing a polyphenolic phase and a tannin phase, and a C1 solution containing a hypotonic prehydrated protein phase.

[0025] S2. After heating the isomaltooligosaccharide solution, slowly add konjac powder and stir to disperse to obtain C2 solution; add the C1 solution to the C2 solution, add a pH adjuster to regulate the pH of the system, and then evaporate the water under negative pressure to reconstruct the hydration layer and obtain the C phase;

[0026] S3. Pump the B-phase concentrate into the C-phase, control the fluid shear and feeding rate, and use the natural acidity of the B-phase to perform in-situ titration and fine-tuning of the C-phase, so that the pH of the system is finally stabilized at 3.8 to 4.0.

[0027] S4. Stop homogenization and continue the cooling process while stirring until the system temperature drops to 35 to 40 degrees Celsius.

[0028] S5. After the system temperature stabilizes, pump in the A phase extract, mix evenly, and then perform online vacuum degassing and aseptic filling to obtain the finished product.

[0029] By employing the above technical solution, and utilizing a composite process of multiphase separation and extraction, polysaccharide matrix hydration layer reconstruction, and in-situ hydrodynamic titration, the stability of the polyphenol-protein coexistence system is improved, degradation of active substances is prevented, and macroscopic rheological properties are maintained. Regarding the principle of the preparation method and the anti-complexation process, the specific mechanism is as follows:

[0030] This invention implements multiphase physical isolation at the source of the process. Specifically, effective components with different physicochemical properties are extracted separately to establish independent solute systems. Components rich in volatile oils and lactones constitute phase A, components rich in polyphenols and tannins constitute phase B, and collagen macromolecules constitute phase C1. This operation directly severs the initial contact pathway between polyphenol molecules and protein macromolecules that are not protected by polysaccharides.

[0031] After forming solution C1, solution C1 is added to solution C2 containing polysaccharides and evaporated to a constant volume under negative pressure. As the volume of free water decreases and the osmotic pressure of the system increases, isomaltooligosaccharide and konjac glucomannan molecules are forced to migrate to the protein surface. During this process, the hydroxyl groups on the polysaccharide molecular chains replace water molecules on the protein surface, and through non-covalent bonds, they self-assemble around the collagen peptides in donkey-hide gelatin and fish collagen, successfully constructing a dense polysaccharide hydration layer with a spatial barrier function, thus forming a stable C-phase matrix.

[0032] Subsequently, during microfluidic acidity titration, the naturally acidic B-phase concentrate was pumped into the matrix flow field. Under high shear force, the high-concentration B-phase stream deformed and broke apart upon contact with the C-phase, dispersing into a micron-sized droplet array. Organic acid molecules within the B-phase then diffused towards the C-phase interface, slowly neutralizing the pre-controlled pH of the C-phase in situ. The rapidly updating flow field ensured a uniform proton concentration distribution, preventing protein isoelectric point precipitation caused by a sharp increase in local acidity.

[0033] Finally, after all easily complexing components are mixed, the system transitions from a high-kinetic-energy state to a low-kinetic-energy state through programmed cooling. The reduced intensity of molecular thermal motion at this point promotes entanglement between polysaccharide polymer chains, gradually forming a three-dimensional pseudoplastic rheological network that locks solid particles and macromolecules within the spatial grid. Phase A is then incorporated at the low-temperature state, thereby ensuring the thermodynamic stability of the volatile components.

[0034] Preferably, in step S1, the raw materials are pre-extracted and processed as follows:

[0035] Preparation of Phase A extract: Angelica sinensis and saffron were added to purified water and dynamically extracted at 45 to 55 degrees Celsius for 1.0 to 2.0 hours. The supernatant was then centrifuged and stored at 4 degrees Celsius in the dark.

[0036] Preparation of phase B concentrate: Add purified water to Rehmannia glutinosa, mulberry and wolfberry, extract at 90 to 95 degrees Celsius and combine the filtrates, then concentrate under vacuum. Stop concentration when the absolute weight of the concentrate reaches 45.0 to 50.0 and keep warm at 60 degrees Celsius for later use.

[0037] Preparation of C1 solution: Add purified water to donkey-hide gelatin powder and fish collagen peptides at 45 to 55 degrees Celsius and stir at low speed for 20 to 40 minutes to form a free-flowing protein aqueous phase without visible particles.

[0038] By employing the above technical solutions, phase A utilizes medium-temperature dynamic extraction parameters, which promotes the dissolution of lipid-soluble components and prevents the high-temperature oxidative degradation of terpenes and glycosides. Phase B uses near-boiling point extraction to ensure cell wall disruption, allowing for the full release of polyphenols and polysaccharides; subsequent concentration to a specific high-temperature range significantly increases the dry matter concentration and osmotic pressure within the system. Solution C1 is maintained at a low-speed hydration rate under medium-temperature conditions, enabling protein molecular chains to acquire sufficient kinetic energy to unfold their tertiary structure. Simultaneously, the low rotation speed eliminates irreversible protein denaturation foam caused by air interface entrainment, maintaining the homogeneity of the aqueous phase.

[0039] Preferably, in step S2, the absolute difference between the absolute saturation of the obtained phase C and the absolute saturation of the phase B concentrate in S1 is less than or equal to 2.0, and the pH of the system is stabilized between 6.5 and 7.0.

[0040] By employing the above technical solution, the absolute hysteresis of phase C is adjusted to a level essentially consistent with that of the concentrate in phase B, eliminating the osmotic pressure gradient at the interface between the two phases. Under these conditions, rapid cross-phase migration of water is prevented, thus preventing the desorption and detachment of the polysaccharide hydration layer bound to the proteins in phase C. Simultaneously, the initial pH of phase C is adjusted to a slightly acidic-neutral range far from the natural isoelectric point of proteins, resulting in a high density of the same charge on the surface of the protein colloidal particles. This provides an anti-flocculation electrostatic protective barrier through double-layer repulsion.

[0041] Preferably, step S3 is implemented as follows: the temperature of phase C is maintained at 55 to 65 degrees Celsius, the concentrate of phase B is pumped into the homogenization emulsification head suction area at the bottom of phase C through a submersible distributor, and the rotor speed is adjusted to maintain the Reynolds number of the macroscopic flow field of the mixture at 5000 to 8000; the pumping volume flow rate of phase B is adjusted to control the pH decrease rate of the mixture at 0.02 to 0.1 pH per minute.

[0042] The specific implementation of step S4 is as follows: a linear or stepped cooling program is executed by a programmable logic controller, with the cooling rate controlled between -0.3 degrees Celsius per minute and -0.8 degrees Celsius per minute. During the cooling process, as the temperature decreases, the speed of the stirring paddle is reduced linearly or stepwise to 30% of the initial speed.

[0043] By employing the above technical solution, the B-phase fluid enters the high-shear region from the bottom subsurface, avoiding fluid eddies and gas entrainment caused by surface feeding. Maintaining the Reynolds number within a specific initial turbulence range provides sufficient fluid kinetic energy to break interfacial tension and promote mass transfer, while the resulting peak shear stress is below the covalent bond breaking threshold of the polysaccharide backbone, protecting the integrity of the rheological macromolecular framework. Strictly limiting the pH decrease rate to less than 0.1 per minute provides ample time for conformational rearrangement relaxation of protein molecules, resisting conformational collapse caused by transient acid stress. During the cooling phase, the decay rate of stirring kinetic energy matches the increase in apparent viscosity due to temperature drop, reducing mechanical friction damage during the critical period of colloidal network coagulation, ensuring the smooth final texture of the composition and the long-term phase stability of the system.

[0044] Thirdly, the present invention provides an application of a herbal plant composition with yin-nourishing and blood-tonifying effects, using the following technical solution:

[0045] Application of a herbal plant composition with yin-nourishing and blood-nourishing effects, wherein the herbal plant composition with yin-nourishing and blood-nourishing effects is used in the preparation of health foods or traditional Chinese medicine preparations with yin-nourishing and blood-nourishing effects.

[0046] By employing the above-mentioned technical solution, and utilizing a physically isolated, stable excipient system with multiple targets of active substances, macromolecular proteins and plant polyphenols are delivered in vivo in a state of high bioavailability. This results in improved intestinal absorption of the nourishing and blood-tonifying active ingredients, and synergistic effects on hematopoietic and cellular antioxidant physiological functions. The inherent pseudoplastic fluid characteristics and macroscopic rheological stability of this composition ensure that the active ingredients are not easily destroyed during processing and storage. Its high-molecular cross-linked network completely eliminates the risk of active ingredient stratification and sedimentation during storage, thus guaranteeing the accuracy of dosage and long-term stability of efficacy in large-scale production of health foods or traditional Chinese medicine preparations.

[0047] This invention provides a herbal plant composition with yin-nourishing and blood-tonifying effects and its applications. It possesses the following beneficial effects:

[0048] 1. This invention employs a technical solution that combines isomaltooligosaccharide solution with konjac flour to construct a polysaccharide matrix, along with a stepwise distribution of protein molecular weight. This achieves the technical effect of forming a steric hindrance hydration layer within the system and physically isolating polyphenols from macromolecules. Compared to existing technologies that directly liquid-combine animal-derived proteins with traditional Chinese medicines rich in plant polyphenols, this invention overcomes the deficiency of polyphenol hydroxyl groups readily cross-linking and flocculating with proteins. It effectively avoids product phase separation caused by irreversible complex precipitation.

[0049] 2. This invention employs a multiphase separation extraction, reconstruction of the polysaccharide hydration layer, and in-situ titration under controlled microfluidic field conditions. This achieves the technical effects of preventing protein precipitation due to acid stress and maintaining the integrity of the rheological macromolecular skeleton. Compared with conventional crude mixing or rapid acid addition techniques in the prior art, this invention solves the problem of instantaneous collapse of protein conformation caused by a sudden increase in local acidity and eliminates the process risk of improper shearing force severing the covalent bonds of the polysaccharide backbone.

[0050] 3. This invention adopts a technical solution of physical isolation and steady-state shaping and construction of a pseudoplastic fluid network, which achieves the technical effects of releasing active ingredients in a free state, improving absorption rate and ensuring long-term resistance to physical sedimentation of the end product. Compared with the conventional liquid Chinese medicine preparation technology that lacks three-dimensional cross-linking network support in the prior art, it solves the shortcomings of low solubility and poor bioavailability of easily complexed components in the digestive tract, and eliminates the problem of uneven dosage caused by component stratification during the product shelf life. Attached Figure Description

[0051] Figure 1 This is a graph showing the dynamic change of transmittance during the phase combination process of the test examples and comparative examples of the present invention;

[0052] Figure 2 The following are low-temperature rheological parameter diagrams for the test examples and comparative examples of the present invention; wherein (a) is a sub-diagram of the apparent viscosity distribution of each test sample, and (b) is a sub-diagram of the initial yield stress distribution of each test sample.

[0053] Figure 3 The following are the accelerated sedimentation and shelf-life physical stability distribution diagrams of the test examples and comparative examples of the present invention; wherein (a) is a sub-diagram of the mass distribution of precipitate after high-speed centrifugation for each sample, and (b) is a sub-diagram of the volume distribution of clear liquid after long-term standing for each sample.

[0054] Figure 4 The following are the retention rate distribution diagrams of thermosensitive and volatile markers in the test examples and comparative examples of the present invention; wherein (a) is a sub-diagram of the retention rate distribution of ligustilide in each sample, and (b) is a sub-diagram of the retention rate distribution of crocin-I in each sample. Detailed Implementation

[0055] 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.

[0056] 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.

[0057] Angelica sinensis, saffron, rehmannia glutinosa, mulberry, and wolfberry are all commercially available conventional Chinese medicinal materials that meet the standards stipulated in the Chinese Pharmacopoeia.

[0058] Donkey-hide gelatin is a solid gelatin made by boiling and concentrating the skin of donkeys (Equus equina). Its main chain contains proline and hydroxyproline domains, with L-hydroxyproline content not less than 5%. Its weight-average molecular weight ranges from 20,000 Da to 80,000 Da, and its natural isoelectric point pH is 4.8.

[0059] Fish collagen peptide, CAS number 9007-34-5, is a mixture of low molecular weight oligopeptides. In its peptide chain structure, glycine residues account for 1 / 3 of the total amino acid residues, and the average molecular weight is between 500 Da and 1500 Da.

[0060] The isomaltooligosaccharide solution is an aqueous solution of a branched oligosaccharide mixture containing α-1,6 glycosidic bonds, with a total dry matter mass fraction ≥70%, of which the oligosaccharides composed of isomaltooligosaccharide, panose, and isomalttriose with a degree of polymerization of 2 to 10 account for more than 50% of the total dry matter mass.

[0061] The CAS number of konjac flour is 37220-17-0. Its main effective polymer component is konjac glucomannan, whose polymer backbone is composed of D-glucose and D-mannose linked alternately by β-1,4 glycosidic bonds. The molar ratio of glucose to mannose is 1:1.6. Its 1% mass concentration aqueous solution has an apparent viscosity of 10000 mPa·s to 25000 mPa·s at 25℃.

[0062] Preparation Example 1:

[0063] This preparation example provides a method for preparing an extract of the volatile phase and the thermosensitive phase (phase A), including the following steps:

[0064] 200g of Angelica sinensis and 10g of saffron were placed in a sealed extraction vessel equipped with a reflux condenser. 2100g of purified water was added, and the jacket heating temperature was controlled to maintain the liquid phase temperature in the vessel at 45℃. Dynamic extraction was performed for 2.0 hours. After extraction, the extract was separated by centrifugation at 10000r / min using a tubular centrifuge. The supernatant was collected and stored in a sealed container at 4℃ in the dark to obtain phase A extract.

[0065] Preparation Example 2:

[0066] This preparation example provides a method for preparing an extract of the volatile phase and the thermosensitive phase (phase A), including the following steps:

[0067] 200g of Angelica sinensis and 20g of saffron were placed in a sealed extraction vessel equipped with a reflux condenser. 2200g of purified water was added. The jacket heating temperature was controlled to maintain the liquid phase temperature in the vessel at 50℃. Dynamic extraction was performed for 1.5 hours. After extraction, the extract was separated by centrifugation at 10000r / min using a tubular centrifuge. The supernatant was collected and stored in a sealed container at 4℃ in the dark to obtain phase A extract.

[0068] Preparation Example 3:

[0069] This preparation example provides a method for preparing an extract of the volatile phase and the thermosensitive phase (phase A), including the following steps:

[0070] 300g of Angelica sinensis and 50g of saffron were placed in a sealed extraction vessel equipped with a reflux condenser. 5250g of purified water was added. The jacket heating temperature was controlled to maintain the liquid phase temperature in the vessel at 55℃. Dynamic extraction was performed for 1.0 hour. After extraction, the extract was separated by centrifugation at 10000r / min using a tubular centrifuge. The supernatant was collected and stored in a sealed container at 4℃ in the dark to obtain phase A extract.

[0071] Preparation Example 4:

[0072] This preparation example provides a method for preparing a polyphenol phase and tannin phase concentrate (phase B), including the following steps:

[0073] 500g of Rehmannia glutinosa, 400g of mulberry, and 400g of wolfberry were placed in an extraction tank, and 10400g of purified water were added. The mixture was extracted twice at 90℃ for 2.0 hours each time. The extracts were combined and filtered, and then pumped into a falling film evaporator for vacuum concentration. The vacuum degree was controlled at -0.09MPa. Concentration was stopped when the absolute value of the concentrate reached 45.0. The natural pH of the system at this time was measured to be 4.0. The concentrate was then kept at 60℃ for later use to obtain phase B concentrate.

[0074] Preparation Example 5:

[0075] This preparation example provides a method for preparing a polyphenol phase and tannin phase concentrate (phase B), including the following steps:

[0076] 800g of Rehmannia glutinosa, 600g of mulberry, and 700g of wolfberry were placed in an extraction tank, and 21,000g of purified water was added. The mixture was extracted twice at 95℃ for 1.5 hours each time. The extracts were combined and filtered, and then pumped into a falling film evaporator for vacuum concentration. The vacuum degree was controlled at -0.08MPa. Concentration was stopped when the absolute value of the concentrate reached 48.0. The natural pH of the system at this time was measured to be 3.9. The concentrate was then kept at 60℃ for later use to obtain phase B concentrate.

[0077] Preparation Example 6:

[0078] This preparation example provides a method for preparing a polyphenol phase and tannin phase concentrate (phase B), including the following steps:

[0079] 1200g of Rehmannia glutinosa, 800g of mulberry, and 1000g of wolfberry were placed in an extraction tank, and 36000g of purified water were added. The mixture was extracted twice at 95℃ for 1.5 hours each time. The extracts were combined and filtered, and then pumped into a falling film evaporator for vacuum concentration. The vacuum degree was controlled at -0.06MPa. Concentration was stopped when the absolute value of the concentrate reached 50.0. The natural pH of the system at this time was measured to be 3.8. The concentrate was then kept at 60℃ for later use to obtain phase B concentrate.

[0080] Preparation Example 7:

[0081] This preparation example provides a method for preparing a hypotonic prehydrated protein phase (C1 solution), including the following steps:

[0082] Add 600g of purified water to the auxiliary mixing tank, heat to 45℃, add 100g of donkey-hide gelatin powder and 200g of fish collagen peptides while stirring at a low speed of 30r / min, keep warm and stir for 40 minutes to form a homogeneous and free-flowing protein aqueous phase without visible particles, which is the C1 solution.

[0083] Preparation Example 8:

[0084] This preparation example provides a method for preparing a hypotonic prehydrated protein phase (C1 solution), including the following steps:

[0085] Add 1300g of purified water to the auxiliary mixing tank, heat to 50℃, add 250g of donkey-hide gelatin powder and 400g of fish collagen peptides while stirring at a low speed of 40r / min, keep warm and stir for 30 minutes to form a homogeneous and free-flowing protein aqueous phase without visible particles, which is the C1 solution.

[0086] Preparation Example 9:

[0087] This preparation example provides a method for preparing a hypotonic prehydrated protein phase (C1 solution), including the following steps:

[0088] Add 2000g of purified water to the auxiliary mixing tank, heat to 55℃, add 400g of donkey-hide gelatin powder and 600g of fish collagen peptides while stirring at a low speed of 50r / min, keep warm and stir for 20 minutes to form a homogeneous and free-flowing protein aqueous phase without visible particles, which is the C1 solution.

[0089] Example 1:

[0090] This embodiment provides a herbal plant composition with yin-nourishing and blood-tonifying effects and its preparation method, including the following steps:

[0091] (1) In the main mixing vessel equipped with a double-layer frame stirring paddle, mechanical bubble breaker and bottom stator and rotor homogenizing emulsifier, add 5000 g of isomaltooligosaccharide solution, heat to 70°C, slowly add 10 g of konjac powder, stir and disperse for 20 minutes to obtain C2 solution.

[0092] (2) Pump the C1 liquid obtained in Preparation Example 8 into the C2 liquid in the main mixing tank, controlling the total material filling volume to not exceed 60% of the total volume of the main mixing tank to reserve space for foaming expansion. Turn on the homogenizing emulsification head and control the stator and rotor speed to make the local shear rate reach 120s. -1 Add an appropriate amount of potassium citrate to forcibly adjust and stabilize the pH of the system at 6.8.

[0093] (3) Turn on the mechanical defoamer and slowly increase the vacuum of the main mixing vessel to -0.05 MPa in a stepwise manner. Evaporate the water slowly at 65°C. When the absolute weight of the system shown by the online refractometer reaches 47.5, release the vacuum to complete the reconstruction of the isotonic steric hydration layer and obtain the C phase. At this time, the absolute difference between the weight of the C phase and the weight of the B phase obtained in Preparation Example 5 (48.0) is 0.5.

[0094] (4) Maintain the temperature of the C-phase main mixing vessel at 60°C. Pump the B-phase concentrate obtained in Preparation Example 5 into the bottom homogenizing head suction area of ​​the C-phase main mixing vessel through a submersible distributor. Adjust the stator and rotor speeds to maintain the Reynolds number of the macroscopic flow field of the mixture at 6500. Link the B-phase feed metering pump with the online pH meter in the main mixing vessel and adjust the pumping volume flow rate of the B-phase to strictly control the pH decrease rate of the mixed system at 0.05 pH / min. Utilize the natural acidity of the B-phase to perform in-situ titration of the C-phase. Subsequently, the citric acid solution can be finely adjusted to finally stabilize the pH of the system at 3.9.

[0095] (5) Stop homogenization, maintain frame stirring, turn on the cooling water in the reactor jacket, and execute linear programmable cooling through the programmable logic controller. The cooling rate is strictly controlled at -0.5℃ / min until the system temperature drops to 40℃. During the cooling period, the stirring speed decreases linearly to 30% of the initial speed as the temperature decreases.

[0096] (6) After the system temperature stabilizes at 40°C, the A phase extract obtained in Preparation Example 2 is pumped in, and after mixing at low speed under normal pressure for 15 minutes, the product is obtained by online vacuum degassing and aseptic filling.

[0097] Example 2:

[0098] This embodiment provides a herbal plant composition with yin-nourishing and blood-tonifying effects and its preparation method, including the following steps:

[0099] (1) In the main mixing vessel equipped with a double-layer frame stirring paddle, mechanical bubble breaker and bottom stator and rotor homogenizing emulsifier, add 4000 g of isomaltooligosaccharide solution, heat to 65°C, slowly add 5 g of konjac powder, stir and disperse for 15 minutes to obtain C2 solution.

[0100] (2) Pump the C1 liquid obtained in Preparation Example 7 into the C2 liquid in the main mixing tank, controlling the total material filling volume to not exceed 60% of the total volume of the main mixing tank to reserve space for foaming expansion. Turn on the homogenizing emulsification head and control the stator and rotor speed to make the local shear rate reach 100s. -1 Add an appropriate amount of potassium citrate to forcibly adjust and stabilize the pH of the system at 6.5.

[0101] (3) Turn on the mechanical defoamer and slowly increase the vacuum of the main mixing vessel to -0.03 MPa in a stepwise manner. Evaporate the water slowly at 65°C. When the absolute hysteresis of the system shown by the online refractometer reaches 43.0, release the vacuum to complete the reconstruction of the isotonic spatial steric hydration layer and obtain phase C. At this time, the absolute difference between the hysteresis of phase C and phase B obtained in preparation example 4 (45.0) is 2.0.

[0102] (4) Maintain the temperature of the C-phase main mixing vessel at 55°C. Pump the B-phase concentrate obtained in Preparation Example 4 into the bottom homogenizing head suction area of ​​the C-phase main mixing vessel through a submersible distributor. Adjust the stator and rotor speeds to maintain the Reynolds number of the macroscopic flow field of the mixture at 5000. Link the B-phase feed metering pump with the online pH meter in the main mixing vessel and adjust the pumping volume flow rate of B-phase to strictly control the pH decrease rate of the mixed system at 0.1 pH / min. Utilize the natural acidity of B-phase to perform in-situ titration of C-phase. Subsequently, the citric acid solution can be finely adjusted to finally stabilize the pH of the system at 4.0.

[0103] (5) Stop homogenization, maintain frame stirring, turn on the cooling water in the reactor jacket, and execute linear programmable cooling through the programmable logic controller. The cooling rate is strictly controlled at -0.3℃ / min until the system temperature drops to 35℃. During the cooling period, the stirring speed decreases linearly to 30% of the initial speed as the temperature decreases.

[0104] (6) After the system temperature stabilizes at 35°C, the A phase extract obtained in Preparation Example 1 is pumped in, and after mixing at low speed under normal pressure for 15 minutes, the product is obtained by online vacuum degassing and aseptic filling.

[0105] Example 3:

[0106] This embodiment provides a herbal plant composition with yin-nourishing and blood-tonifying effects and its preparation method, including the following steps:

[0107] (1) In the main mixing vessel equipped with a double-layer frame stirring paddle, mechanical bubble breaker and bottom stator and rotor homogenizing emulsifier, add 6000 g of isomaltooligosaccharide solution, heat to 75°C, slowly add 15 g of konjac powder, stir and disperse for 30 minutes to obtain C2 solution.

[0108] (2) Pump the C1 liquid obtained in Preparation Example 9 into the C2 liquid in the main mixing tank, controlling the total material filling volume to not exceed 60% of the total volume of the main mixing tank to reserve space for foaming expansion. Turn on the homogenizing emulsification head and control the stator and rotor speed to make the local shear rate reach 150s. -1 Add an appropriate amount of potassium citrate to forcibly adjust and stabilize the pH of the system at 7.0.

[0109] (3) Turn on the mechanical defoamer and slowly increase the vacuum of the main mixing vessel to -0.06 MPa in a stepwise manner. Evaporate the water slowly at 65°C. When the absolute hysteresis of the system shown by the online refractometer reaches 50.0, release the vacuum to complete the reconstruction of the isotonic steric hydration layer and obtain phase C. At this time, the absolute difference between the hysteresis of phase C and phase B obtained in preparation example 6 (50.0) is 0.

[0110] (4) Maintain the temperature of the C-phase main mixing vessel at 65°C. Pump the B-phase concentrate obtained in Preparation Example 6 into the bottom homogenizing head suction area of ​​the C-phase main mixing vessel through a submersible distributor. Adjust the stator and rotor speeds to maintain the Reynolds number of the macroscopic flow field of the mixture at 8000. Link the B-phase feed metering pump with the online pH meter in the main mixing vessel and adjust the pumping volume flow rate of B-phase to strictly control the pH decrease rate of the mixed system at 0.02 pH / min. Utilize the natural acidity of B-phase to perform in-situ titration of C-phase. Subsequently, the citric acid solution can be finely adjusted to finally stabilize the pH of the system at 3.8.

[0111] (5) Stop homogenization, maintain frame stirring, turn on the cooling water in the reactor jacket, and execute linear programmable cooling through the programmable logic controller. The cooling rate is strictly controlled at -0.8℃ / min until the system temperature drops to 38℃. During the cooling period, the stirring speed decreases linearly to 30% of the initial speed as the temperature decreases.

[0112] (6) After the system temperature stabilizes at 38°C, the A phase extract obtained in Preparation Example 3 is pumped in, and after mixing at low speed under normal pressure for 15 minutes, the product is obtained by online vacuum degassing and aseptic filling.

[0113] Example 4:

[0114] This embodiment provides a herbal plant composition with yin-nourishing and blood-tonifying effects and its preparation method, including the following steps:

[0115] (1) In the main mixing vessel equipped with a double-layer frame stirring paddle, mechanical bubble breaker and bottom stator and rotor homogenizing emulsifier, add 5000 g of isomaltooligosaccharide solution, heat to 70°C, slowly add 10 g of konjac powder, stir and disperse for 20 minutes to obtain C2 solution.

[0116] (2) Pump the C1 liquid obtained in Preparation Example 7 into the C2 liquid in the main mixing tank, controlling the total material filling volume to not exceed 60% of the total volume of the main mixing tank to reserve space for foaming expansion. Turn on the homogenizing emulsification head and control the stator and rotor speed to make the local shear rate reach 120s. -1 Add an appropriate amount of potassium citrate to forcibly adjust and stabilize the pH of the system at 6.8.

[0117] (3) Turn on the mechanical defoamer and slowly increase the vacuum of the main mixing vessel to -0.05 MPa in a stepwise manner. Evaporate the water slowly at 65°C. When the absolute hysteresis of the system shown by the online refractometer reaches 49.0, release the vacuum to complete the reconstruction of the isotonic steric hydration layer and obtain phase C. At this time, the absolute difference between the hysteresis of phase C and phase B obtained in preparation example 6 (50.0) is 1.0.

[0118] (4) Maintain the temperature of the C-phase main mixing vessel at 60°C. Pump the B-phase concentrate obtained in Preparation Example 6 into the bottom homogenizing head suction area of ​​the C-phase main mixing vessel through a submersible distributor. Adjust the stator and rotor speeds to maintain the Reynolds number of the macroscopic flow field of the mixture at 7000. Link the B-phase feed metering pump with the online pH meter in the main mixing vessel and adjust the pumping volume flow rate of the B-phase to strictly control the pH decrease rate of the mixed system at 0.08 pH / min. Utilize the natural acidity of the B-phase to perform in-situ titration of the C-phase. Subsequently, the citric acid solution can be finely adjusted to finally stabilize the pH of the system at 3.8.

[0119] (5) Stop homogenization, maintain frame stirring, turn on the cooling water in the reactor jacket, and execute linear programmable cooling through the programmable logic controller. The cooling rate is strictly controlled at -0.6℃ / min until the system temperature drops to 40℃. During the cooling process, the stirring speed is reduced stepwise to 30% of the initial speed as the temperature decreases.

[0120] (6) After the system temperature stabilizes at 40°C, the A phase extract obtained in Preparation Example 2 is pumped in, and after mixing at low speed under normal pressure for 15 minutes, the product is obtained by online vacuum degassing and aseptic filling.

[0121] Example 5:

[0122] This embodiment provides a herbal plant composition with yin-nourishing and blood-tonifying effects and its preparation method, including the following steps:

[0123] (1) In the main mixing vessel equipped with a double-layer frame stirring paddle, mechanical bubble breaker and bottom stator and rotor homogenizing emulsifier, add 5000 g of isomaltooligosaccharide solution, heat to 70°C, slowly add 10 g of konjac powder, stir and disperse for 20 minutes to obtain C2 solution.

[0124] (2) Pump the C1 liquid obtained in Preparation Example 9 into the C2 liquid in the main mixing tank, controlling the total material filling volume to not exceed 60% of the total volume of the main mixing tank to reserve space for foaming expansion. Turn on the homogenizing emulsification head and control the stator and rotor speed to make the local shear rate reach 120s. -1 Add an appropriate amount of potassium citrate to forcibly adjust and stabilize the pH of the system at 6.8.

[0125] (3) Turn on the mechanical defoamer and slowly increase the vacuum of the main mixing vessel to -0.05 MPa in a stepwise manner. Evaporate the water slowly at 65°C. When the absolute weight of the system reaches 44.5 as shown by the online refractometer, release the vacuum to complete the reconstruction of the isotonic spatial steric hydration layer and obtain phase C. At this time, the absolute difference between the weight of phase C and the weight of phase B (45.0) obtained in preparation example 4 is 0.5.

[0126] (4) Maintain the temperature of the C-phase main mixing vessel at 60°C. Pump the B-phase concentrate obtained in Preparation Example 4 into the bottom homogenizing head suction area of ​​the C-phase main mixing vessel through a submersible distributor. Adjust the stator and rotor speeds to maintain the Reynolds number of the macroscopic flow field of the mixture at 6000. Link the B-phase feed metering pump with the online pH meter in the main mixing vessel and adjust the pumping volume flow rate of the B-phase to strictly control the pH decrease rate of the mixed system at 0.04 pH / min. Utilize the natural acidity of the B-phase to perform in-situ titration of the C-phase. Subsequently, the citric acid solution can be finely adjusted to finally stabilize the pH of the system at 4.0.

[0127] (5) Stop homogenization, maintain frame stirring, turn on the cooling water in the reactor jacket, and execute linear programmable cooling through the programmable logic controller. The cooling rate is strictly controlled at -0.4℃ / min until the system temperature drops to 38℃. During the cooling process, the stirring speed is reduced stepwise to 30% of the initial speed as the temperature decreases.

[0128] (6) After the system temperature stabilizes at 38°C, the A phase extract obtained in Preparation Example 2 is pumped in, and after mixing at low speed under normal pressure for 15 minutes, the product is obtained by online vacuum degassing and aseptic filling.

[0129] Comparative Example 1:

[0130] Compared with Example 1, the difference is that phase separation extraction and hydration layer reconstruction are not performed. All the original medicinal materials are boiled together with water to extract and concentrate them. Then, donkey-hide gelatin, fish collagen peptides, isomaltooligosaccharide solution and konjac powder are directly added and stirred evenly. After natural cooling, they are bottled. Everything else is the same.

[0131] Comparative Example 2:

[0132] Compared with Example 1, the difference lies in the change of the feeding sequence and pH environment. Potassium citrate is not added to lock the weakly alkaline pH in the C phase preparation stage, and the B phase concentrate obtained in Preparation Example 5 is directly mixed with the C1 solution obtained in Preparation Example 8 and then added to the C2 solution containing isomaltooligosaccharide solution. All other aspects are the same.

[0133] Comparative Example 3:

[0134] Compared with Example 1, the difference is that the micro negative pressure evaporation and volume fixation of water is not turned on during the preparation stage of phase C, which results in the absolute weight difference between phase B and phase C being much greater than 2.0 when phase B is pumped into phase C. All other aspects are the same.

[0135] Comparative Example 4:

[0136] Compared with Example 1, the difference is that the feed volume flow rate of phase B is not controlled during the phase combination process. Phase B is directly and rapidly poured into phase C within 1 minute. The pH of the system drops extremely quickly, and the pH drop rate is not controlled to be within 0.1 pH / min. All other aspects are the same.

[0137] Comparative Example 5:

[0138] Compared with Example 1, the difference is that after the phase combination is completed, the homogenization is stopped and the specific linear cooling program is not executed. Instead, the heating is stopped directly and the system is allowed to cool naturally to 40°C at room temperature. All other aspects are the same.

[0139] Comparative Example 6:

[0140] Compared with Example 1, the difference is that konjac powder is not added to the formulation system when preparing C2 liquid, but everything else is the same.

[0141] Test Example 1:

[0142] Test objective: To demonstrate that isotonic control and extremely slow transisoelectric point titration block the polyphenol-protein complexation reaction.

[0143] Test steps:

[0144] 1. The mixed fluids of Examples 1 to 5 and Comparative Examples 2 to 4 that were in the phase combination stage in the corresponding preparation process were selected as test objects.

[0145] 2. Install a UV-Vis spectrophotometer with a flow cell in series on the external circulation pipeline of the main mixing vessel. Set the optical path of the flow cell to 1 mm and fix the detection wavelength at 600 nm.

[0146] 3. Before the phase combination process of each test object begins, the photometer is baseline calibrated using purified water at the same temperature as the operating temperature, and the transmittance is set to 100% at this time.

[0147] 4. Record the initial transmittance before phase merging, i.e., before the polyphenol phase has been pumped in or just before it is about to be pumped in. Then start the corresponding polyphenol phase pumping program, read and record the transmittance value online every 10 minutes until phase merging is complete, and continue mixing for 10 minutes under the same stirring conditions, and record the final transmittance.

[0148] The corresponding test data are shown in Table 1.

[0149] Table 1: Dynamic Changes in Transmittance During Phase Synthesis Process in Examples and Comparative Examples

[0150]

[0151] Conclusion: Based on Table 1 and Figure 1 The data from the examples and comparative examples show significant differences in transmittance during the phase mixing stage. The change in turbidity during the mixing of the polyphenol and protein phases directly reflects the intensity of the internal macromolecular complexation reaction. Previous experimental observations often revealed that such mixtures easily become instantly turbid, while in Examples 1 to 5, the transmittance only decreased slowly and slightly throughout the entire mixing cycle, ultimately remaining above 78%. This slight decrease in transmittance is mainly due to the introduction of the natural color of the plant extracts themselves, rather than the generation of suspended particulate matter. This result effectively confirms that the steric hydration barrier layer constructed by isomaltooligosaccharides plays a fundamental physical isolation role under weakly alkaline conditions.

[0152] With extremely gentle isoelectric point titration and strict isotonic control, although the surface charge state of protein molecules reverses upon reaching the isoelectric point, large-scale polydentate hydrogen bonding with polyphenols does not occur. Comparative examples with altered system boundary conditions reveal that Comparative Example 2, which disrupts the feeding sequence, exhibits an extremely low transmittance of 15.2% in the initial stage. This indicates that the protein, without pre-coated oligosaccharides, spontaneously lowers the system's Gibbs free energy upon contact with plant polyphenols, resulting in irreversible flocculation and precipitation. Comparative Example 3, which omits the isotonic volume adjustment step, shows a precipitous drop in transmittance to 32.1% within the first ten minutes after phase mixing. This rapid loss of transmittance indicates that the significant osmotic pressure difference generated during phase mixing disrupts mass transfer equilibrium, instantly stripping the hydration layer attached to the peptide surface and causing the protective mechanism to fail.

[0153] To further investigate the impact of the hydrodynamic timescale, Comparative Example 4 employed an uncontrolled rapid pumping method. Due to insufficient microscopic relaxation time for the macromolecular network, the rapid acidic titration caused collagen to instantly lose its electrostatic repulsion due to the like charge. The exposed proline-rich binding sites rapidly cross-linked with free phenolic hydroxyl groups, causing the transmittance to plummet to 12.4% at the ten-minute mark. These differentiated high-frequency sampling data quantitatively transformed the previously macroscopically invisible transient phase transition process, directly demonstrating the necessity of employing a hydrodynamic and thermodynamic compatibility coupling control strategy to sever the complexation pathway.

[0154] Test Example 2:

[0155] Test objective: To demonstrate that programmed cooling, in synergy with konjac flour, generates the specific rheological network required for suspension and bottom support, without forming dead glue.

[0156] Test steps:

[0157] 1. The ointment products prepared in Examples 1 to 5 and Comparative Examples 5 and 6 and continuously stored at 4°C for 24 hours were selected as the rheological test objects.

[0158] 2. Using a rotational rheometer equipped with a coaxial cylindrical test fixture, the temperature of the test system is precisely maintained at 4°C using a Peltier temperature control system. A suitable amount of the sample to be tested is carefully transferred into the test gap and kept at a constant temperature for 5 minutes to eliminate residual structural stress generated during sample loading.

[0159] 3. Perform steady-state shear scan test, setting the shear rate range to 0.01 s. -1 up to 100s -1 Data was collected using a logarithmic model, and the shear stress and apparent viscosity values ​​at different shear rates were recorded online.

[0160] 4. Based on the collected flow curve data, the Herschel-Balkley model was used in the basic analysis software built into the rheometer to perform nonlinear regression fitting on the data in the low shear region, calculating the initial yield stress and rheological property index of the sample. Simultaneously, the shear rate at 10 s⁻¹ was extracted. -1 The apparent viscosity value at that time is used as a reference value for pouring fluidity.

[0161] The corresponding test data are shown in Table 2.

[0162] Table 2: Test data of rheological parameters at 4℃ for examples and comparative examples

[0163]

[0164] Conclusion: Based on Table 2 and Figure 2 The data shows that the rheological parameters of the present invention, represented by the examples, exhibit a specific range distinct from traditional processes at a low temperature of 4°C. In previous early-stage formulation development observations, it was often found that high-concentration animal protein complexes tend to solidify at low temperatures. Here, the apparent viscosity of Examples 1 to 5 is maintained in the range of 3650 to 4890 mPa·s. This viscosity range ensures suitable fluidity without clinging to the container walls when poured from the packaging. The rheological index values ​​are all less than 1, confirming the pseudoplastic fluid nature of the system. Its initial yield stress is between 2.87 and 4.12 Pa. This stress threshold constructs a continuous rheological network at the microscale, sufficient to resist Stokes sedimentation of internal submicron particles under gravity, firmly trapping suspended matter within the network nodes without interfering with macroscopic shear flow.

[0165] A thorough investigation into the effect of temperature gradients on the conformational transition of macromolecules revealed a dramatic thermodynamic runaway in Comparative Example 5, which involved unprogrammed cooling. This sample, after being allowed to cool naturally at ambient temperature immediately after heating ceased, exhibited a dramatic increase in apparent viscosity to 82400 mPa·s and an initial yield stress as high as 86.30 Pa. These values, exceeding the range of normal fluids, indicate that the conformational transition of collagen polypeptide chains from random coils to triple helices was excessively rapid. Disordered and dense physical cross-linking occurred between the polypeptide molecules and oligosaccharides, causing the entire system to transform into an irreversible gel with lost flowability. This phenomenon confirms that disordered cooling without controlled cooling slope disrupts the ordered arrangement of the microstructure, leading to an irreparable loss of fluidity.

[0166] The skeletal support role of konjac glucomannan in the polymer network is highlighted by the data from Comparative Example 6. After removing konjac flour from the formulation, the initial yield stress of the sample sharply decreased to 0.12 Pa, while the rheological index climbed to 0.95, indicating that the system almost degenerated into a Newtonian fluid lacking an internal network structure. Due to the absence of non-covalent entanglement anchors provided by rigid polysaccharide chains, the loose bond between collagen and isomaltoose alone cannot establish a yield support phase with sufficient strength under low shear fields. The liquid matrix loses its mechanical basis for supporting suspended particles, and the vertical migration of particles due to gravity cannot be contained by fluid resistance. These objective mechanical detection data verify the engineering feasibility of constructing an anti-agglomeration steric hindrance network using a specific cooling slope combined with trace amounts of konjac polysaccharide.

[0167] Test Example 3:

[0168] Test objective: To macroscopically compare the final effects of the present invention with traditional and incomplete processes in preventing coagulation and precipitation.

[0169] Test steps:

[0170] 1. The herbal ointment products of Examples 1 to 5 and Comparative Examples 1 to 6, which were filled and matured at room temperature for 24 hours, were selected as the objects of stability evaluation.

[0171] 2. Perform accelerated dehydration test by centrifugation. Accurately weigh 50.0 g of each sample and transfer them to pre-weighed and dried centrifuge tubes. Place the tubes in a high-speed refrigerated centrifuge and centrifuge continuously at 8000 r / min for 30 minutes at 25°C. After centrifugation, discard the supernatant and transfer the centrifuge tubes containing the bottom precipitate to a vacuum drying oven at 60°C until constant weight. Accurately weigh the absolute dry weight of the precipitate and convert it to the percentage of precipitate mass relative to the initial sample amount.

[0172] 3. Perform a natural settling stratification test to simulate shelf-life storage behavior. Measure 100 ml of each test sample and pour it into a 100 ml graduated glass graduated cylinder with a stopper. Seal the cylinder and place it in an incubator at a controlled temperature of 25°C and a relative humidity of 60% for 6 months. After the set time, read and record the volume of the clear, non-suspended liquid layer that appears at the top of the sample under natural light, and calculate its percentage of the total clear liquid volume.

[0173] The corresponding test data are shown in Table 3.

[0174] Table 3: Accelerated Centrifugation and Long-Term Static Settling Test Data of Examples and Comparative Examples

[0175]

[0176] Conclusion: Based on Table 3 and Figure 3The data shows a significant difference in physical stability between the examples and traditional and incomplete processes. The dry weight percentage of the centrifuged sediment in Examples 1 to 5 was strictly controlled below 0.2%, and the proportion of water separation after simulated long-term settling was also extremely close to zero. In the early pilot-scale production stages, the research team often found that these complex systems containing high concentrations of macromolecular proteins and polyphenols would form a dense, difficult-to-stir sediment layer on the bottom of the tank after several weeks of storage. The extremely low centrifugal stripping amount obtained in the tests now effectively demonstrates the effectiveness of the isoelectric point shift and the competitive hydration shielding mechanism of oligosaccharides. The protein backbone is firmly locked inside the sterically hindered hydration layer, completely eliminating the prerequisite for cross-linking with plant tannins and agglomerating into high-density sediment.

[0177] In contrast, Comparative Example 1, which employed a traditional co-decoction process, exhibited extremely severe phase separation defects, with a sedimentation rate as high as 15.42%. Free polyphenols released from broken plant cells rapidly surrounded and hinged collagen polypeptide chains in the high-temperature aqueous phase without any physical isolation. This thermodynamically spontaneously formed massive network complex has a density far exceeding that of the continuous phase medium, inevitably undergoing downward macroscopic migration under gravity, resulting in a top supernatant precipitation of up to 18.5%. This is the physical root cause of the severe sedimentation and stratification phenomenon commonly observed in commercially available traditional herbal ointments during their shelf life. A process lacking a core control parameter also fails to establish a complete protective system. Comparative Examples 2 to 4, lacking isotonic constant volume or rapid crossing of the isoelectric point, also showed significant flocculation separation; sudden changes in local osmotic pressure and charge reversal deprived the macromolecular network of microscopic relaxation time. The instantaneous collapse of the hydration layer leads to irreversible side reactions. The resulting fine flocs, even after being subjected to high-intensity centrifugal compression, still have a dry matter accumulation of over 9.5%, which is sufficient to form visible turbidity and sedimentation under normal pressure.

[0178] Observing systems where rheological support changes can reveal another type of mechanical failure mode. In Comparative Example 6, the pseudoplastic suspension bearing capacity originally provided by the non-covalent entanglement of polysaccharides disappeared after the removal of trace amounts of konjac flour. The tiny particles, unable to be supported by the initial yield stress of the liquid matrix, underwent Stokes sedimentation, resulting in a slow precipitation of 8.1% clear liquid layer at the top of the graduated cylinder. Although Comparative Example 5 did not show a large amount of loose particles settling to the bottom, the high water separation rate of 8.7% revealed another extreme problem caused by uncontrolled natural cooling. Uncontrolled protein conformational changes led to a violent gel dehydration and shrinkage phenomenon inside the gel, i.e., the macromolecular cross-linked network forcibly squeezed out the free water encapsulated inside. These objective weighing and volume measurement data constitute the most direct evidence for the aforementioned multi-fluid physical protection mechanism, proving that long-term homogeneity of complex multiphase systems can be achieved without relying on conventional large-dose suspending agents by precisely intervening in macromolecular compatibility.

[0179] Test Example 4:

[0180] Test objective: To demonstrate the significant advantages of the phase-separation low-temperature extraction and temperature rise control process of this invention in terms of retention of effective components compared to traditional extract collection processes.

[0181] Test steps:

[0182] 1. The final products of Examples 1 to 5 and Comparative Example 1, which uses the traditional decoction and extracting process, were selected as the chromatographic analysis objects. At the same time, the corresponding batches of raw medicinal materials were retained as the reference substances for calculating the theoretical input amount.

[0183] 2. Accurately weigh 2.0 g of each finished product sample and place it in a stoppered conical flask. Add methanol and extract by ultrasonication for 30 minutes. After cooling, shake well and filter through a 0.45 μm microporous membrane. Take the filtrate as the test solution. At the same time, prepare standard reference solutions of ligustilide and crocin-I.

[0184] 3. Quantitative determination was performed using a high-performance liquid chromatograph equipped with a diode array detector. An octadecylsilane-bonded silica column was used, with a methanol-water mobile phase for gradient elution. The wavelength was set to 440 nm for the detection of crocin-I and switched to 320 nm for the detection of ligustilide. The peak areas of each characteristic peak were recorded.

[0185] 4. The absolute mass of the two types of markers in the finished product is calculated using the external standard method. The mass is then divided by the theoretical total amount of substances measured in the extract of the original medicinal material under the same feed ratio to obtain the retention rate data in percentage form.

[0186] The corresponding test data are shown in Table 4.

[0187] Table 4: Quantitative Test Data on Retention Rate of Active Ingredients in Examples and Comparative Examples

[0188]

[0189] Conclusion: Based on Table 4 and Figure 4 The data shows that the phase-separation low-temperature extraction and phase-combination process used in the examples exhibits a significant order-of-magnitude advantage in the retention of core active pharmaceutical ingredients. In previous sample tracking studies of traditional large-scale Chinese medicine production, prolonged high-temperature decoction and open-air concentration operations are often accompanied by severe degradation and volatilization. In Comparative Example 1, the final retention rate of ligustilide was only 12.46%, and crocin-I dropped to 18.73%. This extremely low retention of active ingredients confirms that the conventional mixed decoction and extract-forming method systematically damages both the heat-sensitive and volatile phases. High-intensity heat accumulation breaks the chemical bonds of polyphenols and glycosides, while simultaneously causing a large amount of volatile lactones to escape at the boiling gas-liquid interface.

[0190] Examples 1 to 5, by redesigning the feeding and extraction sequence, consistently increased the final retention rates of the two types of markers to over 85%. Examining the physicochemical mechanism behind this data breakthrough, volatile components were extracted in a separate A phase at room temperature or low temperature, and then submerged pumped into the main mixing vessel after cooling to below 40°C, completely avoiding the intense molecular thermal motion of the system in a high-energy state. Easily dissipating lactone molecules were rapidly encapsulated within the steric hindrance network of konjac and oligosaccharide polymers possessing initial yield stress, significantly reducing their diffusion flux to the outside world due to the high apparent viscosity of the pseudoplastic fluid. Regarding the degradation problem of heat-sensitive components, the exponential increase of the thermodynamic reaction rate constant with increasing temperature provided an intervention strategy. Polyphenols and glycosides, which are highly susceptible to hydrolysis and oxidative degradation, were placed in separate pipelines, and in-situ titration and rapid mass transfer were performed using a homogenization system within a specific weakly acidic or weakly alkaline window, successfully avoiding the cumulative thermal damage caused by prolonged exposure to a boiling water bath. The obtained quantitative chromatographic data not only confirmed that the aforementioned anti-precipitation mechanism did not interfere with the chemical stability of the active ingredients, but also proved the engineering application value of this rheological and thermodynamic coupling intervention strategy in improving the overall formulation quality of modern herbal ointments from a material basis perspective.

[0191] 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 herbal plant composition with yin-nourishing and blood-tonifying effects, characterized in that, Made from the following ingredients in parts by weight: Angelica sinensis 200-300 parts; 10-50 parts saffron; 500-1200 parts of Rehmannia glutinosa; 400-800 servings of mulberries; 400-1000 servings of goji berries; 100-400 parts of donkey-hide gelatin powder; Fish collagen peptides, 200-600 parts; 4000-6000 parts of isomaltooligosaccharide solution; 5-15 portions of konjac powder.

2. The herbal composition with yin-nourishing and blood-tonifying effects according to claim 1, characterized in that, The raw materials are in the following weight proportions: 200 parts Angelica sinensis, 20 parts saffron, 800 parts Rehmannia glutinosa, 600 parts mulberry, 700 parts wolfberry, 250 parts donkey-hide gelatin powder, 400 parts fish collagen peptide, 5000 parts isomaltooligosaccharide solution, and 10 parts konjac powder.

3. The herbal composition with yin-nourishing and blood-tonifying effects according to claim 1, characterized in that, The main chain of the donkey-hide gelatin powder contains proline and hydroxyproline domains, wherein the L-hydroxyproline content is not less than 5%, the weight-average molecular weight distribution of the donkey-hide gelatin powder is between 20,000 Da and 80,000 Da, and the natural isoelectric point pH value is 4.8; the average molecular weight of the fish collagen peptide is between 500 Da and 1,500 Da, and the glycine residues in the peptide chain structure of the fish collagen peptide account for 1 / 3 of the total amino acid residues.

4. The herbal composition with yin-nourishing and blood-tonifying effects according to claim 1, characterized in that, The total dry matter mass fraction of the isomaltooligosaccharide solution is ≥70%, wherein the oligosaccharides composed of isomaltose, panose, and isomalttriose with a degree of polymerization of 2 to 10 account for more than 50% of the total dry matter mass; the main effective component of the konjac powder is konjac glucomannan, and the apparent viscosity of a 1% mass concentration aqueous solution of the konjac powder at 25°C is 10000 mPa·s to 25000 mPa·s.

5. The herbal composition with yin-nourishing and blood-tonifying effects according to claim 1, characterized in that, The raw materials also include a pH adjuster, which is one or a combination of potassium citrate and citric acid.

6. The method for preparing the herbal plant composition with yin-nourishing and blood-tonifying effects according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Provide, in proportion, an A-phase extract containing a volatile phase and a thermosensitive phase, a B-phase concentrate containing a polyphenolic phase and a tannin phase, and a C1 solution containing a hypotonic prehydrated protein phase. S2. After heating the isomaltooligosaccharide solution, slowly add konjac powder and stir to disperse, to obtain solution C2. The C1 solution was added to the C2 solution, and a pH adjuster was added to regulate the pH of the system. Then, the water was evaporated under negative pressure and the hydration layer was reconstructed to obtain the C phase. S3. Pump the B-phase concentrate into the C-phase, control the fluid shear and feeding rate, and use the natural acidity of the B-phase to perform in-situ titration and fine-tuning of the C-phase, so that the pH of the system is finally stabilized at 3.8-4.

0. S4. Stop homogenization and continue the cooling process while stirring until the system temperature drops to 35-40℃. S5. After the system temperature stabilizes, pump in the A phase extract, mix evenly, and then perform online vacuum degassing and aseptic filling to obtain the finished product.

7. The method for preparing the herbal plant composition with yin-nourishing and blood-tonifying effects according to claim 6, characterized in that, In step S1, the raw materials are pre-extracted and processed as follows: Preparation of phase A extract: Angelica sinensis and saffron were added to purified water and dynamically extracted at 45-55℃ for 1.0-2.0 hours. The supernatant was then centrifuged and stored at 4℃ in the dark. Preparation of phase B concentrate: Add purified water to Rehmannia glutinosa, mulberry and wolfberry, extract at 90-95℃ and combine the filtrates, then concentrate under vacuum. Stop concentration when the absolute weight of the concentrate reaches 45.0-50.0 and keep warm at 60℃ for later use. Preparation of C1 solution: Add purified water to donkey-hide gelatin powder and fish collagen peptides at 45-55℃ and stir at low speed for 20-40 minutes to form a free-flowing protein aqueous phase without visible particles.

8. The method for preparing the herbal plant composition with yin-nourishing and blood-tonifying effects according to claim 6, characterized in that, In step S2, the absolute difference between the absolute saturation of the obtained phase C and the absolute saturation of the phase B concentrate in S1 is controlled to be ≤2.0, and the pH of the system is adjusted to be stable at 6.5-7.

0.

9. The method for preparing the herbal plant composition with yin-nourishing and blood-tonifying effects according to claim 6, characterized in that, The specific implementation method of step S3 is as follows: maintain the temperature of phase C at 55-65℃, pump the phase B concentrate into the homogenization emulsification head suction area at the bottom of phase C through a submersible distributor, adjust the stator and rotor speed to maintain the Reynolds number of the macroscopic flow field of the mixture at 5000-8000; adjust the pumping volume flow rate of phase B to control the pH decrease rate of the mixed system at 0.02-0.1pH / min. The specific implementation of step S4 is as follows: a linear or stepped cooling program is executed by a programmable logic controller, with the cooling rate controlled between -0.3℃ / min and -0.8℃ / min. During the cooling process, as the temperature decreases, the speed of the agitator is reduced linearly or stepwise to 30% of the initial speed.

10. The use of the herbal plant composition with yin-nourishing and blood-tonifying effects according to any one of claims 1-5 in the preparation of health food or traditional Chinese medicine preparations with yin-nourishing and blood-tonifying effects.

Images