Liquefied traditional chinese medicine and preparation method therefor

Abstract

The present application discloses a liquefied traditional Chinese medicine, consisting of the full components of traditional Chinese medicinal materials or decoction pieces, water, and an optional carrier or excipient. The viscosity of the liquefied traditional Chinese medicine ranges from 6000 cp to 500000 cp. The present application further discloses a preparation method for the liquefied traditional Chinese medicine

Description

Liquefied Chinese medicine and preparation method thereof Field of the Invention

[0001] The present application relates to the field of traditional Chinese medicine, in particular to liquefied traditional Chinese medicine prepared from traditional Chinese medicine materials or traditional Chinese medicine slices, water, and optional carriers or excipients, and also to a preparation method thereof. Background Art

[0002] Conventional decoction, extraction and other preparation processes will damage the nutrients and active substances in Chinese medicinal materials, and many effective ingredients will be destroyed by factors such as temperature, oxygen, and ultraviolet rays.

[0003] On the one hand, browning occurs, which is the core factor of the universal black color of traditional Chinese medicine. This includes Maillard reaction and enzymatic browning.

[0004] On the other hand, the drug components are protected by the cell wall, and there are concentration gradient differences in extraction and dissolution, and the penetration of large molecular organic matter is limited. After heating, the protein denatures, which aggravates the constraints on the components and makes it difficult to effectively transfer the effective ingredients in the original medicinal materials. Existing medicinal material slices are mostly used in the decoction mode, which not only causes browning problems, but also the drug components are protected by the cell wall, and there are concentration gradient differences in dissolution, and the penetration of large molecular organic matter is limited; after heating, the protein denatures, which aggravates the constraints on the components. Not only is it difficult for large molecular insoluble organic matter to enter the decoction, but the volatile components are lost during the cooking process, and insoluble inorganic substances such as gypsum are difficult to dissolve in the decoction, so the consumption of medicinal materials is large. The common dosage of decoctions is generally about 10 times that of powders, which can probably be attributed to the above factors.

[0005] Summary of the Invention

[0006] This application proposes a new technical solution, which uses Chinese medicinal materials or decoction pieces as raw materials, grinds them with water to break the wall, so that all the ingredients of the medicinal materials or decoction pieces are exposed to water. According to needs, medicinal carriers or excipients can be added to obtain liquefied Chinese medicine containing water and all the ingredients of Chinese medicinal materials or decoction pieces, which is a uniform and stable semi-solid.

[0007] According to one aspect, the present application provides a liquefied Chinese medicine comprising the entire composition of Chinese medicinal materials or decoction pieces, water, and an optional carrier or excipient, and having a viscosity within the range of 6,000 to 500,000 cp. The lower limit of the viscosity of the liquefied Chinese medicine is determined by a test standard where a 10 ml syringe with the plunger removed and 10 ml of the liquefied Chinese medicine is filled with no self-flow for at least 3 seconds.

[0008] On the one hand, the liquefied Chinese medicine of the present application can expose all the ingredients of solid medicinal materials or decoction pieces and migrate them into water, so that the ingredients can be quickly absorbed. Moreover, in the presence of water, a carrier or excipient can be added when necessary, and then a good physical stable state is formed by grinding (preferably vibration grinding). On the other hand, the liquefied Chinese medicine avoids oxidation and browning caused by the extraction process, avoids changes in composition caused by various factors, and achieves that the material composition or material basis of the liquefied Chinese medicine and the medicinal materials or decoction pieces does not change.

[0009] According to some embodiments, the Chinese medicinal materials of the liquefied Chinese medicine of the present application are selected from animal, plant or mineral Chinese medicinal materials, but do not include fresh berries.

[0010] According to some embodiments, the viscosity of the liquefied Chinese medicine may be 10,000 to 330,000 cp, such as 13,000 to 180,000 cp.

[0011] According to some embodiments, the viscosity of the liquefied Chinese medicine of the present application is measured by a rotational viscometer.

[0012] According to some embodiments, the cells of the plant and animal Chinese medicinal materials in the liquefied Chinese medicine of the present application are in a broken cell state, with a cell breaking rate of more than 80%, and even more than 95%.

[0013] The liquefied Chinese medicine of the present application is a semi-solid or viscous substance that is not stratified, uniform, and stable.

[0014] According to some embodiments, the Chinese herbal medicine or decoction pieces may be single or compound Chinese herbal medicine or decoction pieces.

[0015] The preparation process of the liquefied Chinese medicine of the present application comprises wet grinding the starting materials of Chinese medicinal materials or decoction pieces, adding water and / or a water-containing substance. The water-containing substance may be, for example, an aqueous extract (e.g., a water extract of a natural medicinal product) or an aqueous carrier or excipient. The grinding is preferably vibratory grinding.

[0016] According to some embodiments, in the preparation of the liquefied Chinese medicine, water extract can be used to replace part or all of the water in the wet grinding process, and water is ensured to be the continuous phase.

[0017] According to some embodiments, in wet grinding, the ratio of the total weight of solid material (such as Chinese medicinal materials or decoction pieces and optional pharmaceutical carriers or excipients) to water is 1:1 to 1:10, preferably 1:1 to 1:5, 1:1 to 1:3, or 1:2 to 1:3.

[0018] The preparation methods of liquefied traditional Chinese medicines disclosed herein include a one-step method and a two-step method. The one-step method employs only wet grinding. The two-step method includes dry grinding prior to wet grinding, wherein dry grinding involves grinding the solid material without adding water. The grinding includes, but is not limited to, vibration grinding. Dry grinding preferably results in cell wall disruption.

[0019] According to some embodiments, in the preparation process of the present application, no classification is required during grinding, that is, the Chinese medicinal materials or decoction pieces do not need to be graded by particle size. No need for particle size classification means that the Chinese medicinal materials or decoction pieces do not need to be processed according to particle size, but are directly ground. The preparation process of the present invention can achieve high viscosity.

[0020] The medicinal substance basis of the liquefied Chinese medicine is not significantly changed compared to the starting Chinese medicinal materials or Chinese medicinal slices. The medicinal substance basis is not significantly changed, which means that the main chemical components are not changed.

[0021] The liquefied Chinese medicine of the present application optionally includes a pharmaceutical carrier or excipient. The carrier of the present application is an inactive substance that can deliver the active ingredient into the body or cells. The excipient includes flavoring agents, antioxidants, preservatives, and other auxiliary materials that do not change the medicinal ingredients. These can be added during or after grinding.

[0022] The liquefied Chinese medicine of the present application can be a liquefied Chinese medicine made from a single Chinese medicinal material or a decoction piece, or can be a compound liquefied Chinese medicine obtained by compounding a liquefied Chinese medicine made from a single Chinese medicinal material or a decoction piece according to demand.

[0023] The liquefied Chinese medicine of the present application can be a liquefied Chinese medicine made from compound Chinese medicinal materials or decoction pieces, or can be a compound liquefied Chinese medicine obtained by combining liquefied Chinese medicine made from single Chinese medicinal materials or decoction pieces according to demand.

[0024] The flavoring agents include but are not limited to honey, sugar or sugar alcohol (such as white sugar, fructose, lactose, dextrin, fructose syrup, xylitol, erythritol, isomaltulose, oligoisomaltitol, etc.), salt, milk and dairy products, flavors, spices and other excipients that do not change the ingredients of the medicine.

[0025] This application uses the interfacial interaction liquefaction technology of traditional Chinese medicine to achieve high-density energy and material transfer, breaking through the existing barriers to material and energy transfer. This technology uses mechanical energy to break through the barriers between the interface of the particle cluster and the particles, thereby forming multiple single particles. The surface energy of a single solvent is used to isolate the single particles so that they cannot contact the interface of the original particle cluster. Kinetic energy is used to force the single particles into the solvent, achieving non-similar dissolution and efficient full-component liquefaction.

[0026] Technical advantages:

[0027] 1. A completely innovative liquefaction system that improves yield, multi-component, reduces costs and combines temperature control and antioxidant capabilities.

[0028] 2. The liquefied Chinese medicine of the present application does not need to be boiled, does not require donkey-hide gelatin or other glues (deer antler glue, tortoise shell glue, etc.) to make a paste, does not need to be melted, and does not need to add sugar to make a paste. A major factor in the existing paste prescription process is to add sugar for the convenience of preparation.

[0029] 3. The liquefied Chinese medicine of the present application has stable properties and does not stratify. The liquid (paste, slurry) maintains its original color and avoids oxidative browning. It has certain advantages in color (taking rose and roselle as examples), and becomes translucent after being diluted 1000 times. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 shows the characteristic spectra of Astragalus slices (corresponding to the slice solution in the figure) and liquefied slices (i.e. liquefied Chinese medicine) (UV detector)

[0031] Figure 2 shows the characteristic spectra of Astragalus slices (corresponding to the slice solution in the figure) and liquefied slices (evaporative light scattering detector)

[0032] Figure 3 shows the characteristic spectra of Radix Glycyrrhizae Radix and Liquorice Radix pieces (UV detector)

[0033] Figure 4 shows the characteristic spectra of ginger slices and liquefied slices (UV detector)

[0034] Figure 5 shows the characteristic spectra of ginseng slices and liquefied slices (UV detector)

[0035] Figure 6 shows the characteristic spectra of Radix Rehmanniae and liquefied Radix Rehmanniae (UV detector)

[0036] Figure 7 shows the characteristic spectra of cassia twig slices and liquefied slices (UV detector)

[0037] Figure 8 shows the characteristic spectra of jujube slices and liquefied slices (UV detector)

[0038] Figure 9 shows the characteristic spectra of Fructus Corni decoction pieces and liquefied decoction pieces (UV detector)

[0039] Figure 10 shows the characteristic spectra of Polygonum multiflorum slices and liquefied slices (UV detector)

[0040] Figure 11 shows the characteristic spectra of Sichuan Cyathulae slices and liquefied slices (UV detector)

[0041] Figure 12 shows the characteristic spectra of Scrophulariaceae decoction pieces and liquefied decoction pieces (UV detector)

[0042] Figure 13 shows the characteristic spectra of Rhizoma Alismatis and liquefied Rhizoma Alismatis (UV detector)

[0043] Figure 14 shows the comparison of AUC0-72 of the three components after rats were gavaged with liquefied slices of Astragalus and traditional decoction (the left column of each group is traditional decoction, and the right column is liquefied slices)

[0044] Figure 15 shows the comparison of AUC0-72 of the two components after rats were gavaged with liquefied pieces of Burdock Fruit and traditional decoction (the left column of each group is traditional decoction, and the right column is liquefied pieces)

[0045] FIG16 shows a structural diagram of an example of a grinding device

[0046] FIG17 is a structural diagram showing another example of a grinding device.

[0047] FIG. 18 shows the viscosity test results of the liquefied Chinese medicine of the present invention.

[0048] Detailed Description of the Invention

[0049] The preparation method of the present application can be carried out under an inert gas protection atmosphere, for example, filled with an inert gas including but not limited to nitrogen, argon, helium, carbon dioxide, etc. and combinations thereof.

[0050] Dry grinding:

[0051] Using dry products as raw materials meets the characteristics of raw materials for Chinese herbal medicine slices or Chinese medicinal materials. In addition, from the perspective of crushing or grinding, fibrous materials are stronger when wet, so dry grinding is more efficient and can easily achieve micron-level particle size characteristics.

[0052] Dry grinding can achieve good particle size distribution (normal distribution) and has a good stacking effect.

[0053] The crushing (grinding) temperature is controlled within 40°C, preferably within 30°C, and more preferably within 20°C. Special varieties such as heat-sensitive materials such as frankincense and myrrh can be controlled within 10°C, and preferably within 0°C.

[0054] Dry grinding (crushing) equipment may include, but is not limited to, a rotor mill (rotor crusher), a ball mill, a jet mill, and a vibration mill, preferably a vibration mill.

[0055] The fineness of dry grinding is controlled within 80 mesh, optimized to be controlled within 120 mesh, optimized to be controlled at -100 mesh ≥ 95%, optimized to be controlled at -150 mesh ≥ 95%, optimized to be controlled at -200 mesh ≥ 95%, optimized to be controlled at -300 mesh ≥ 95%. The finer particle state is used to increase the force-bearing particles in the wet grinding (crushing) process, improve the grinding (crushing) efficiency, and improve the narrowing of the particle size distribution.

[0056] If dry grinding is used, the workload of grinding can be focused on dry grinding, which is beneficial to reduce the load of the wet process, reduce working time and temperature rise, and reduce the risk of microbial growth.

[0057] Wet grinding:

[0058] The main function of the wet grinding process for plant or animal medicinal materials is to stretch the fiber components, dissolve the water-soluble components in water, and elute the water-insoluble or poorly soluble components embedded, attached or wrapped in the structures of cellulose, polysaccharides, proteins, chitin, etc., and expose them to water.

[0059] If dry grinding was previously used, wet grinding (comminution) should be performed after effective dry grinding. During wet grinding, high viscosity is achieved by adjusting the amount of water added and the fineness of the material. A vibrating mill is preferred for wet grinding. This achieves effective dispersion and dissociation through a well-balanced force distribution. Because fibrous materials significantly swell when exposed to water, wet grinding often produces coarser results than dry grinding.

[0060] The viscosity of the material in wet grinding is characterized by a high-viscosity paste or slurry (semi-fluid). High viscosity achieves more effective grinding efficiency. The mechanism is that high viscosity is more conducive to the grinding medium to have a higher probability of applying force to the particles during each friction / collision, and the particles are more effectively attached to the surface of the medium. Compared with the slurry state, the particles are less likely to escape from the medium, thereby improving the grinding efficiency.

[0061] Due to the high viscosity grinding solution, the only classification method to be selected is screening and / or filtration.

[0062] The preferred grinding (crushing) equipment is a vibration mill, as there is no need to classify the medicinal materials by coarseness or return the coarse particles to the classification process for recirculation grinding. The mechanism is that the use of rods as grinding (crushing) media is more advantageous than the point-like force of other media such as spheres or short rods with the same aspect ratio. The material is subjected to linear grinding (crushing) force between the grinding (crushing) media of the vibration mill.

[0063] Because linear force preferentially destroys large particles, coarse particles can be processed without a grading process. Grading processes (screening and filtration) struggle to classify higher-viscosity materials. Achieving a favorable viscosity not only increases particle contact probability, further improving grinding (crushing) efficiency and particle size uniformity, but also enhances slurry stability through high viscosity, shortening the production process and facilitating piping connections, cleaning (CIP), and material changes.

[0064] In the wet grinding process of the present application, the weight ratio of the Chinese medicinal materials or decoction pieces to water is 1:1 to 1:10, for example, 1:1 to 1:5, 1:1 to 1:3, or 1:2 to 1:3. The weight of water represents the total weight of the water added during the wet grinding and the water of any hydrated substances.

[0065] The preparation process of the present application preferably adopts a liquefaction production line, which is a fully pipelined, fully enclosed, and fully automatic system, with the terminal connected to sterilization and filling, equipped with a pipeline material recovery system, and realizing CIP (online cleaning) and SIP (online sterilization) throughout the line.

[0066] In the preparation process of the present application, the amount of water added should not be too much. Under the condition of pursuing equal volume of particles, an effective stacking effect is achieved. It can not only improve the physical stability of the slurry, avoid sedimentation and segregation, increase the drug concentration and increase the liquid osmotic pressure. Lower the pH value, for example, pH <4.6 can be sterilized at normal pressure. Due to the equal volume shape of the particles (the spherical shape is a perfect equal volume shape, that is, the cross-sectional area through the center is equal), it is easy to achieve a ball effect, which can effectively reduce the slurry extrusion pressure. The bulk viscosity of the stacking effect achieved by high concentration of high equal volume particles can form good physical stability and high fluidity.

[0067] The liquefied Chinese medicine of the present application is a non-Newtonian fluid. When at rest, it is in a high viscosity state close to that of a solid. When stirred and sheared, it has good fluidity, and as the shearing continues, the viscosity continues to decrease until it reaches a lower viscosity, also known as a pseudoplastic fluid.

[0068] The particle size of the solids in the liquefied Chinese medicine of the present application is generally between 3 and 80 microns, for example, 3 to 70 microns, 7 to 60 microns, or 7 to 50 microns. For fibrous Chinese medicinal materials or decoction pieces, the particle size is 15 to 50 microns, for example, 15 to 40 microns. This particle size is generally referred to as d50 or dav.

[0069] Physical stability:

[0070] A key function of this preparation process is wet dissociation, exposing the components to water. The focus is on the "beating" (impact, knocking) process to better stretch and expand the fibers, rather than simply pursuing finer particle size. The goal is to expose more hydroxyl groups, including but not limited to fibers and proteins, to bind more water through hydrogen bonds, facilitating the formation of a good volume effect and network structure. This not only helps achieve physical stability but also reduces the proportion of free water in the system, thereby reducing the conditions for microbial survival and reproduction.

[0071] During wet grinding, the cellulose in the medicinal material (decoction pieces) is stretched, freeing the hemicellulose, exposing more hydrogen bonds to bind with water. Proteins also have a similar effect, forming more bound water, especially when appropriate sterilization methods are used to avoid the denaturation and dehydration of proteins caused by continuous high heat, which can lead to loss of water-binding capacity.

[0072] Starch also has good hydrogen bonding strength in the gelatinized state (similar to glutinous rice balls). Varieties with high starch content require high-pressure spray sterilization to gelatinize the starch to help achieve good physical stability.

[0073] Under the conditions of good microparticle precision compounding, the network structure formed by the combination of cellulose, hemicellulose, protein, saponin, organic acid, alkaloids, etc. can help prevent starch from aging and losing water (bound water).

[0074] Minimizing the water content during wet grinding is beneficial for achieving particle stacking effects and variable skeletons to reduce the sedimentation of solid components (water-insoluble) and water analysis. It can also increase the difficulty of bacterial movement, thereby reducing reproduction.

[0075] The formation of the sponge state of liquefied Chinese medicine requires the use of a knocking force, similar to the way of beating glutinous rice cakes and fish balls, to open the fibers and allow water to penetrate into the microscopic tissues. It does not simply rely on the fineness of grinding.

[0076] After the finished product is stirred or subjected to other external forces, water is released from the "sponge" and becomes a flowable continuous phase, thus achieving fluidity. As stirring time increases, more water becomes the flowable continuous phase, and the apparent viscosity decreases until the water content of the "sponge" reaches the lowest equilibrium value, at which point the viscosity no longer decreases, forming an equilibrium value.

[0077] After the movement reaches the low viscosity state, it is still for a period of time, and then the stirring test is started again. The viscosity value will return to the previous shear / reduction state.

[0078] During the transportation process, the pipe wall has little direct impact on the transportation resistance of the finished product. The reason is that the continuous phase is mainly water, which has low viscosity and low relative movement speed.

[0079] This alternating viscosity characteristic is precisely what allows liquefied Chinese medicine (or decoction pieces) to be stored stably in a static state without adding auxiliary materials, avoiding sedimentation, and maintaining good fluidity during transportation (extrusion). Analysis suggests that this beneficial effect may be due to the "variable skeleton system" formed by water absorption / water precipitation. The variable skeleton system refers to a network structure formed by overlapping fiber components that absorb and expand, forming a skeleton similar to a sponge. It can be compressed and rebounded to achieve water discharge / water absorption.

[0080] Because laser particle size diffractometers can have inaccuracies in characterizing the complex structure of traditional Chinese medicines, particularly the non-isovolume characteristics of traditional Chinese medicine fibers, measuring particle size distribution alone cannot accurately represent the degree of cell wall disruption. The goal of this invention is to expose the medicinal ingredients for easier absorption. Excessive grinding should not be used, as this will disrupt the "variable skeleton system" and reduce stability.

[0081] The present application can adopt a fully enclosed, non-graded grinding (crushing) method, and the difficult-to-crush fiber parts with a long growth cycle will not be treated as waste residue according to the conventional preparation process. After reasonable grinding, the stability state of the "variable skeleton system" of the present application is just achieved.

[0082] Following the principles of traditional Chinese medicine (TCM) inheritance and innovation, a single herb is a small compound, and different parts of the herb at different growth stages may contain different ingredients. The pulverization / grinding process of this technical solution is ingredient-independent, and selection is not made based on the varying pulverization difficulty characteristics of different herb parts. Therefore, the production process of this invention does not produce conventional medicinal residues.

[0083] During vibration grinding (crushing), the probabilistic force application frequency (including uniformity) can be adjusted by adjusting the macroscopic force application time (vibration grinding time). The microscopic force application state can be adjusted by adjusting the macroscopic force application magnitude. This means adjusting the critical impact velocity of the grinding body by adjusting the vibration acceleration and frequency of the grinding drum. In the formula for calculating the momentum experienced by plant fibers, F△t = M△V, M corresponds to the weight of the grinding body, △V is related to the acceleration of gravity and frequency, F corresponds to the product of the weight of the grinding body and the acceleration of gravity, and △t is subject to frequency. To achieve sufficient momentum, mass M is equally important, in addition to velocity △V. In traditional rotor and airflow grinding, M = Chinese medicinal particles. The mass of these tiny particles is far greater than the difference in △V between the two, M = medium weight. The performance comparison is obvious.

[0084] During the wet vibration grinding process, M is large enough, and through 4 to 7 times the acceleration of gravity, its force is enough to resist the restraint and restraint of high-viscosity materials, thereby achieving grinding efficiency through effective impact force.

[0085] The preparation process of the present application can use vibration grinding, and its medium can be, for example, a cylindrical rod. The biggest difference from a sphere is that the grinding force applied by this medium is linear, which is more conducive to preferentially grinding large particles compared to the point-like force applied by a sphere. This is the core element for achieving non-classified grinding (crushing). In addition, the mass M of the rod-shaped medium is much greater than that of the sphere, and the impact force is more effective for tough fibrous materials. During the process of passing through the grinding body, it is continuously subjected to high-frequency impacts of 8 to 31 Hz, which can achieve high efficiency through a better grinding probability.

[0086] During vibration, the vibration pattern is circular or elliptical, and the grinding media rotates at high speed, in the same direction and at the same speed as the excitation motor. This creates a combination of positive and shear forces, effectively stretching the cellulose fibers and allowing water to penetrate the fiber structure, forming effective hydrogen bonds. The presence of polysaccharides, saponins, and proteins in traditional Chinese medicines creates a certain emulsification effect between the oil and water. Combined with the packing effect of the high solids content and excellent thixotropy, this achieves a harmonious balance of stability and fluidity.

[0087] Under high viscosity conditions, achieving TCM liquefaction through compression, shear, linear, and high-frequency impact forces is the core of establishing the stability of TCM liquefaction.

[0088] Commonly used grinding equipment includes non-compression grinding, rotor-type grinding (hammer, needle, high shear, etc.); compression grinding, high-energy ball milling (stirred mill, sand mill, etc.). For Chinese herbal medicine (decoction pieces), both dry and wet processes require classification. The preparation method of the present invention can achieve high viscosity without classification.

[0089] The control core of the vibration grinding adopted in this application is the fluidized motion state of the material in the mill, which helps to achieve that larger particles are subjected to force first and are crushed first to achieve high efficiency. This is also the fundamental reason why the crushing and grinding (crushing) process can be achieved without classification, with sufficient impulse and fluidization self-selection. Without classification, many redundant links can be omitted, the original flavor has no waste residue, the structure is simple and easy to change materials, the cleaning parts are reduced, CIP and SIP can be achieved, and it has strong adaptability. This technical solution can adapt to almost all Chinese medicinal materials.

[0090] Vibration grinding parameters

[0091] Mill material: In order to avoid metal friction and mixing, the vibrating grinding parts in contact with the material include but are not limited to ceramic materials, cemented carbide materials, and special wear-resistant steel. The Rockwell hardness shall not be less than 31HRC, the optimized hardness shall not be less than 45HRC, the optimized hardness shall not be less than 50HRC, the optimized hardness shall not be less than 60HRC, and the optimized hardness shall not be less than 87HRC.

[0092] Under wet grinding conditions, the mill material includes but is not limited to alumina, zirconia, aluminum nitride, etc., including but not limited to zirconia, toughened zirconia, TZP (yttria toughened zirconia), alumina toughened zirconia, silicon nitride, silicon carbide / boron carbide composite ceramics, aluminum nitride and other high hardness materials.

[0093] The grinding media used in the present invention can be, for example, balls or short rods.

[0094] The diameter of the dielectric ball is 8 mm to 31 mm, further optimized to 9 to 16 mm, further optimized to 13 to 22 mm, further optimized to 17 to 26 mm, and further optimized to 21 to 31 mm.

[0095] The dielectric short rod is a short cylinder with the same diameter as the height. The diameter is further clarified to be 8mm to 31mm, further optimized to be 9 to 16mm, further optimized to be 13 to 22mm, further optimized to be 17 to 26mm, and further optimized to be 21 to 31mm.

[0096] The diameter of the dielectric rod is 8 mm to 38 mm, further optimized to 9 to 16 mm, further optimized to 13 to 22 mm, further optimized to 17 to 26 mm, and further optimized to 21 to 31 mm.

[0097] The vibration grinding device can include two operating modes: intermittent and continuous.

[0098] Grinding device

[0099] The liquefied Chinese medicine of the present application is not limited to a certain grinding device. For example, the grinding devices of Figures 16 and 17 can be used for dry and wet grinding. An example of another grinding device is described in Chinese patent application No. 202310403640.6.

[0100] According to some embodiments, the liquefied Chinese medicine of the present application is prepared by the following grinding device, which comprises:

[0101] A grinding cylinder, the grinding cylinder is used to accommodate the material to be ground, and the grinding cylinder is provided with a feed port and a discharge port at opposite ends thereof;

[0102] a vibration mechanism, the vibration mechanism being connected to the grinding cylinder via a connecting piece, and the vibration mechanism being capable of driving the grinding cylinder to vibrate;

[0103] A spring is provided, through which the vibration mechanism is connected to a supporting point.

[0104] In at least one embodiment, a rod-shaped grinding medium is provided inside the grinding cylinder, and an end joint is connected to the end of the grinding cylinder. The end joint includes a joint body and a protrusion. The joint body is cylindrical with an opening at one axial end. A plurality of protrusions are connected to the bottom of the joint body, and the protrusions can block the passage of the grinding medium.

[0105] In at least one embodiment, a through hole is provided on a peripheral wall of the joint body, a pipe connecting portion is connected to the through hole, and the pipe connecting portion is communicated with an inner cavity of the joint body.

[0106] In at least one embodiment, the vibration grinding device also includes a cleaning vibration mechanism, which is connected to the counterweight portion or the cleaning vibration mechanism constitutes a part of the counterweight portion, and the amplitude and / or vibration acceleration of the cleaning vibration mechanism is smaller than the amplitude and / or vibration acceleration of the vibration mechanism.

[0107] In at least one embodiment, the vibration modes of the vibration mechanism and the cleaning vibration mechanism are circular vibration or elliptical vibration, the amplitude of the vibration mechanism is 2 to 9 mm, and the vibration frequency of the vibration mechanism is 8 to 50 Hz.

[0108] In at least one embodiment, the vibration mechanism includes a motor and an exciter, the output shaft of the motor is connected to the exciter, the grinding cylinder is cylindrical, the output shaft of the motor is parallel to the central axis of the grinding cylinder, the axis perpendicular to the vibration trajectory of the vibration mechanism is parallel to the output shaft of the motor, and the exciter is connected to the side wall of the grinding cylinder.

[0109] In at least one embodiment, the grinding drum is rotatably connected to the connecting member, so that the grinding drum can be switched between a grinding state and a discharge state.

[0110] In the grinding state, the axis of the grinding cylinder extends in the horizontal direction; in the discharging state, the axis of the grinding cylinder extends in the vertical direction.

[0111] In at least one possible embodiment, the feed port and the discharge port are disposed at two axial ends of the grinding drum, and the feed port and the discharge port are connected to pipelines.

[0112] For example, referring to Figure 16, there is a grinding cylinder 1, a vibration mechanism 2, a spring 3, a counterweight 4 and a partition 5. The vibration mechanism 2 includes a motor 21 and an exciter 22. The motor 21 can be set on the base 101 on the base plate 100 or the base plate 100. The output shaft of the motor 21 is connected to the exciter 22. The exciter 22 includes an eccentric wheel. The exciter 22 excites vibration through the rotation of the eccentric wheel. The vibration mode of the vibration mechanism 2 can be elliptical or circular, and the axis perpendicular to the vibration trajectory of the vibration mechanism 2 is parallel to the output shaft of the motor 21. The exciter 22 can be connected to the support point through the spring 3. One end of the spring 3 can be connected to the support point, and the other end of the spring 3 can be connected to the exciter 22. The support point can be located at the base 101 on the base plate 100 or at the base plate 100. The spring 3 can be a coil spring, a leaf spring, etc., and the spring 3 can be a compression spring.

[0113] The counterweight 4 can be connected to the vibrator 22. The counterweight 4 and the grinding drum 1 are located on opposite sides of the vibration mechanism 2. The counterweight 4 can balance the mass of the components on both sides of the vibration mechanism 2. In Figure 1, the grinding drum 1 is located on the left side of the vibration mechanism 2, and the counterweight 4 is located on the right side of the vibration mechanism 2.

[0114] The mass of the counterweight 4 can be similar to the vibration mass of the mill drum 1. The vibration mass of the mill drum 1 includes the mass of the mill drum, the mass of the material being ground, and the mass of the grinding media described below. For example, the mass of the counterweight 4 can differ from the vibration mass of the mill drum 1 by less than 20%. With the axis of the vibration mechanism 2 as the center point, the product of the torque and the lever arm of the counterweight 4 and the mill drum 1 (including the material being ground and the grinding media) is similar. For example, the product of the torque and the lever arm of the counterweight 4 and the product of the torque and the lever arm of the mill drum 1 can differ by less than 30%, preferably by less than 20%, and more preferably by less than 10%.

[0115] The grinding drum 1 can be connected to the vibrator 22 via a connector 11. The output shaft of the motor 21 is parallel to the central axis of the grinding drum 1. The partition 5 can be provided with a through hole, through which the connector 11 can pass. During grinding, the grinding drum 1 is sealed, preventing air from contacting the material inside the grinding drum and reducing the chance of oxidation.

[0116] By adopting the above-mentioned grinding device, at least one of the following beneficial effects can be obtained.

[0117] (1) The cleaning vibration mechanism can make the tailings form a certain fluidized state, helping the tailings to be discharged from the grinding cylinder along with the gas.

[0118] (2) The grinding medium applies force to the material to be ground by shearing, compressing and crushing, so that tissues with similar overall sizes are crushed or ground at the same time. During the crushing or grinding process, no drug residue will be produced due to particle size classification, and many redundant classification and crushing steps can be omitted.

[0119] (3) During in-situ cleaning, the cleaning vibration mechanism can stimulate the vibration of the grinding cylinder, causing the grinding media to move slightly, achieving good elution to help the tailings discharge from the grinding cylinder and avoid residue.

[0120] (4) The end joint can block the abrasive medium during in-situ cleaning, and the cleaning effect is good, and the material is not easy to remain.

[0121] During grinding, with a power supply frequency of 50 Hz, the vibration frequency of the grinding drum 1 can be 8 to 50 Hz, with 10 to 30 Hz being the preferred frequency, 12 to 26 Hz being the preferred frequency, and 12 to 13 Hz, 15 to 17 Hz, or 23 to 26 Hz being the preferred frequency. In another example, with a power supply frequency of 50 Hz, the vibration frequency of the grinding drum 1 can be 10 to 31 Hz, with 12 to 15 Hz, 16 to 20 Hz, or 24 to 29 Hz being the preferred frequency. The amplitude (single amplitude, i.e., vibration radius) of the grinding drum 1 can be 2 to 9 mm, with 3 to 5 mm, 5 to 8 mm, or 4 to 6 mm being the preferred frequency. The vibration mode of the grinding drum 1 can be circular or elliptical.

[0122] Preferably, the vibration frequency of the grinding drum 1 may be 8 Hz to 50 Hz, the amplitude may be 2 mm to 9 mm, and the vibration acceleration may be 2 g to 10 g.

[0123] Cell wall disruption as the core technical indicator - heterogeneity characteristics and particle morphology

[0124] Traditional Chinese medicine, which is mainly derived from natural plants or animals, has completely different material properties from chemical drugs. The cell tissue structure carried by each particle will be different.

[0125] In the conventional non-compression crushing (grinding) process, the so-called micropowder, fine powder and coarse powder, which are distinguished according to the difficulty of crushing, represent the characteristics of different cell tissue parts, and their component contents are different.

[0126] Discarding large particles that are difficult to crush through airflow classification will inevitably cause component segregation, which does not include the loss and segregation of volatiles.

[0127] Given the heterogeneous nature of Chinese medicinal materials, it's inappropriate to compare the pulverization performance of different pulverization equipment and processes solely based on particle size. Conventional pulverization methods produce fine powders that are easily crushed, coarse powders that are difficult to crush, and waste residues that cannot be crushed after repeated cycles. Different pulverization methods produce different finished products. For example, airflow pulverization cannot address the issue of volatile components. Both the classification of waste residues and the loss of volatile components can alter the fundamental nature of Chinese medicinal materials.

[0128] The present invention aims to break down the cell wall, allowing the active ingredients to be released from the protective cell wall and dissolved / dispersed in water. Furthermore, the preparation process does not require classification to remove large particles, and a closed preparation method can be used to avoid volatile component loss.

[0129] On this basis, taking the wall breaking rate as the main parameter control point rather than particle size control as the main parameter should be advantageous and more suitable for the technical requirements of the liquefaction system.

[0130] Traditional Chinese medicine, which is mainly derived from natural plants or animals, has completely different material properties from chemical drugs. The cell tissue structure carried by each particle will be different.

[0131] In the conventional non-compression crushing (grinding) process, the so-called micropowder, fine powder and coarse powder, which are distinguished according to the difficulty of crushing, represent the characteristics of different cell tissue parts, and their component contents are different.

[0132] Discarding large particles that are difficult to crush through airflow classification will inevitably cause component segregation, which does not include the loss and segregation of volatiles.

[0133] Due to the non-uniform material characteristics of Chinese medicinal materials, it is not reasonable to compare the crushing effects based solely on particle size when using different crushing equipment and processes. Conventional crushing methods turn easily crushed materials into fine powders, and difficultly crushed materials into coarse powders. Materials that cannot be crushed after repeated cycles become waste residues. The finished products obtained by different crushing methods are different. For example, air flow crushing cannot solve the problem of volatile components. Whether it is grading waste residues or loss of volatiles, the basic substance of Chinese medicine will change. The present invention aims to break the cell wall so that the active ingredients are dissociated from the protection of the cell wall and dissolved / dispersed in water. In addition, the preparation process does not need to use a grading method to remove large particles, and the closed preparation method also avoids the loss of volatiles. The important technical feature of the present invention is the full composition, that is, the grinding process does not produce waste residues, and the loss of volatiles can also be avoided, which is the basic element to avoid changes in the basic substance of Chinese medicine.

[0134] The upper and lower limits of fluidity, the upper limit standard, take a 10ml syringe and fill it with the liquefied Chinese medicine of this application, the extrusion pressure is not more than 300N, for example, the extrusion pressure is not more than 150N, for example, not more than 90N. The lower limit standard of fluidity, take a syringe, fill it with no less than 10ml, remove the plunger, and it will not flow out for at least 3 seconds, for example, at least 6 seconds, or at least 8 seconds. If the Chinese medicinal materials or pieces contain volatile substances, it can be prepared in a closed environment. The liquefied pieces in this application refer to liquefied Chinese medicines prepared by the preparation process of this application. Liquefied Chinese medicine refers to liquefied Chinese medicines prepared by the preparation process of this application from Chinese medicinal materials or pieces.

[0135] The present application realizes the non-Newtonian fluid formed by the stacking effect by increasing the solid content (reducing the water content) of the liquefied slices, has good thixotropy, is high viscosity (favorable for achieving good stability) in a static state, and reduces viscosity (favorable for achieving good filling fluidity) during stirring. In order to achieve good physical stability within the shelf life without adding a thickener, it is avoided or reduced including but not limited to unstable phenomena such as water separation, precipitation, and crystallization. A further effect is that the slurry with a high solid content can also reduce / limit the activity of bacteria. The liquefied Chinese medicine of the present application can be prepared without adding auxiliary materials or auxiliary agents such as preservatives and stabilizers. With the original flavor as the criterion, the cell wall is physically destroyed, thereby removing the barrier and adsorption carrier for the release of the components, and the components are dissolved / dispersed / free in water, so that the power of the medicine is more effectively brought into play. These are the advantages of the liquefied Chinese medicine of the present application. DETAILED DESCRIPTION

[0136] The technology of the present application is illustrated below through specific preparation examples and drawings, but the present application is not limited to these examples.

[0137] (1) Preparation Example

[0138] Example 1: Cinnabar liquefaction of traditional Chinese medicine, one-step process, discontinuous vibration mill.

[0139] Take 1000g of cinnabar and use a Chinese medicine grinder to crush it for 20s to break the large pieces into pieces less than 10mm. Take out the cinnabar powder, add 800ml of pure water to premix, and grind it with a wet vibration mill for 15min until it is d 50 The particles are smaller than 6 microns and are sterilized at 85℃ for 30 minutes after bagging. The particle size is measured by laser particle size diffractometer (the same below).

[0140] Table 1:

[0141] The solid content in the table refers to the content of medicinal materials or decoction pieces in the finished product, which is calculated based on the added amount, the same below.

[0142] Viscosity test method: the same below

[0143] Viscometer Brand: Fangrui Model: DVTV-1T

[0144] Rotor number: R6 / R7;

[0145] Container: 200ml beaker with 200g sample

[0146] Speed ​​10-20rpm;

[0147] The test time is 20-30 minutes.

[0148] Temperature: 20℃

[0149] The viscosity in the table indicates that the viscosity was measured with 30 min of same-position stirring, i.e., the rotor was stirred at the same position for viscosity detection, and the viscosity values ​​(same below) were obtained from the shortest to the longest stirring time. In the present embodiment, the viscosity values ​​varied from 18,000 to 15,450 from the shortest to the longest stirring time. The change in viscosity shows that the liquefied Chinese medicine obtained is a non-Newtonian fluid (same below).

[0150] Example 2: Realgar liquefaction of traditional Chinese medicine, one-step process, discontinuous vibration mill.

[0151] Take 1000g of realgar and use a Chinese medicine grinder to crush it for 30s to break the large pieces into pieces less than 1mm. Then add 1000ml of pure water to the obtained realgar coarse powder and premix it. Then wet vibrate grind it for 1h until the mixture is d 50 The discharged particles are smaller than 7 microns and sterilized at 85℃ for 30 minutes after bagging.

[0152] Example 3: Longan liquefaction Chinese medicine, one-step process. Continuous vibration mill

[0153] Take 3kg of longan pulp and add 8kg of water to soak thoroughly, add it into the high-speed mixing grinder, add 6kg of ice cubes at the same time, start the machine for 30s to break the material into coarse pulp, mix the pulp and pump it into the wet vibration mill until the material is crushed into fine particles to d 50 Less than 37 microns, sterilized at 85℃ for 30 minutes after packaging.

[0154] Example 4: One-step process. Continuous colloid mill + continuous vibration mill (wet vibration mill continuous process)

[0155] Take 3kg of wolfberry and add 5kg of water to soak thoroughly, gradually add to the colloid mill, and add ice cubes at a ratio of 30% of wolfberry. Turn on the colloid mill for 20 minutes to grind the material into a pulp, then filter it through a 100-mesh sieve, return the sieve material to the colloid mill and repeat the above steps until all the material passes through the 100-mesh sieve, and pump the sieve material to the wet continuous vibration grinding device to grind into a pulp to d 50 The particles are smaller than 26 microns, and then sterilized in series with ultra-high temperature (UHT) sterilization at 135℃ for 10s, and then bagged according to the aseptic cold filling scheme.

[0156] The viscosity test results show that the liquefied Chinese medicine is a non-Newtonian fluid (see Figure 18).

[0157] Example 5: One-step process. Continuous vibration mill (wet batch circulation process)

[0158] 5 kg of Indigo naturalis was mixed with 13 kg of water. The mixture was then fed into an 8 L wet vibrating mill using a screw pump at 32 Hz. Two or more hoppers were used for alternating feeding and receiving. The grinding time was 50-80 min, and the fineness was determined to be 95% of -300 mesh (tested by water sieve). The slurry was bagged and sterilized at 85°C for 30 min.

[0159] Example 6: One-step process. Vibration mill (batch cycle process)

[0160] Take 30kg of peach kernels and add them evenly into the gap between the rollers of a two-roller grinder (double-roller grinder). After the double scrapers discharge the material, add 10-20kg of pure water and stir evenly. Then enter wet vibration grinding to form a slurry. Use a micrometer to detect if the slurry is less than 31 microns, which is qualified. After bagging, sterilize at 85℃ for 30 minutes.

[0161] Example 7: One-step process. Continuous vibration mill (wet vibration mill continuous process)

[0162] Take 300kg of cleaned fresh Polygonatum odoratum, cut it into small pieces, then add it into a Chinese medicine beater to crush it for 15s, and crush it into small particles less than 3mm. The obtained fresh Polygonatum odoratum particles are gradually and continuously added to the grinder, and 2 to 3 grinders are connected in series to wet grind until d 50 The particles are smaller than 37 microns, and then sterilized in series with ultra-high temperature instantaneous sterilization (UHT) at 135℃ for 15s, and then bagged according to the aseptic cold filling scheme.

[0163] Example 8: Two-step process, dry rotor grinding + air flow grinding + vibration grinding.

[0164] 30kg of pearls were crushed with a continuous rotor mill so that all the pearl powder could pass through an 80-mesh sieve. Then the pearl powder was crushed with a jet mill to obtain a d 90 ≤10μm. The obtained pearl powder was mixed with 50kg of pure water and fed to a vibration mill (5L) by a screw pump for batch circulation wet grinding. The discharge material was tested for particle size d 90 ≤5μm, sterilize at 85℃ for 30min after discharging and bagging.

[0165] Example 9: Two-step process, dry rotor grinding + continuous wet vibration grinding

[0166] Take 100kg of red ginseng and dry it at 60℃ for 8-16h until the water content of the red ginseng is ≤8%. The dried material is crushed to 95% of -120 mesh by a rotor mill. The obtained red ginseng powder is mixed with 200kg of water and then continuously pumped to wet vibration grinding. The mixture is circulated back and forth between the mill and the material tank for 3 times until d 50The particles are smaller than 26 microns, and then sterilized in series with ultra-high temperature instantaneous sterilization (UHT) at 135℃ for 5s, and then bagged according to the aseptic cold filling plan.

[0167] Example 10: Two-step process, dry vibration milling + continuous wet vibration milling

[0168] Take 100 kg of Panax notoginseng and dry it at 70℃ for 10 hours until the moisture content of Panax notoginseng is ≤6%. The dried material is crushed by dry vibration mill for 13 minutes to make the 200 mesh screening rate of Panax notoginseng fine powder reach 95% or above. The obtained Panax notoginseng fine powder is mixed with 300 kg of pure water and then continuously pumped to vibration wet grinding. The material is circulated back and forth between the mill and the material tank for 3 times until d 50 If the particles are smaller than 28 microns, they can be sterilized in series with ultra-high temperature (UHT) sterilization at 135°C for 5 seconds and then bagged according to aseptic cold filling procedures. Alternatively, they can be sterilized at 85°C for 30 minutes after grinding and bagging.

[0169] Example 11: Two-step process: batch dry vibration milling + continuous wet vibration milling

[0170] 20kg of Astragalus was placed in an ultrasonic cleaning machine with a power of 720W for 20 seconds, then the moisture was controlled and dried at 70℃ for 4-10 hours to make the moisture content of Astragalus ≤6%. The dried Astragalus was added to a Chinese medicine grinder for coarse crushing for 15 seconds. The Astragalus coarse powder was subjected to dry vibration grinding for 13 minutes to make the fine powder 300 mesh sieving rate reach 95% or above. The Astragalus fine powder was transferred to a powder-liquid mixer, mixed with 60kg of pure water, and continuously pumped to wet vibration grinding until d 50 The material is discharged after the particles are less than 31 microns, and then sterilized in series with ultra-high temperature instantaneous sterilization (UHT) at 135℃ for 5s. The resulting slurry is filled according to the aseptic cold filling plan.

[0171] Example 12: Two-step process: dry vibration milling + continuous wet vibration milling

[0172] 20kg of roasted licorice was put into dry vibration mill for dry grinding for 15min, so that the 300 mesh sieving rate of fine powder reached 95% or above. The roasted licorice powder was transferred to powder-liquid mixer, added with 60kg of pure water and mixed, and then put into continuous wet vibration mill for grinding until d 50 The particles are smaller than 40 microns, and then sterilized in series with ultra-high temperature instantaneous sterilization (UHT) at 135℃ for 5s, and then filled according to the aseptic cold filling plan.

[0173] Example 13: Two-step process: dry vibration milling + continuous wet vibration milling

[0174] 30kg of Schisandra chinensis was placed in an ultrasonic cleaning machine with a power of 720W for 10 seconds, then the water content was controlled and dried at 60℃ for 10-28 hours to make the water content of Schisandra chinensis ≤6%. After drying, the Schisandra chinensis was put into a dry vibration mill for dry grinding for 15 minutes to make the fine powder 300 mesh screening rate reach 95% or above. Nitrogen was filled during the grinding process. The Schisandra chinensis fine powder was transferred to a powder-liquid mixer, 45kg of pure water was added and mixed, and then continuously pumped to a continuous wet vibration mill for grinding until d 50 The particles are smaller than 23 microns, and then sterilized in series with ultra-high temperature instantaneous sterilization (UHT) at 135℃ for 3s, and then filled according to the aseptic cold filling plan.

[0175] Example 14: One-step process, discontinuous vibration mill

[0176] Take 500g of Indigo Naturalis 240g, Alum 240g and Borneol 24g (prescription for oral ulcer powder) according to the ratio, grind with 400ml of pure water in a vibration grinder for 15min until d 50 The particles are smaller than 8 microns and are sterilized after being bagged. The sterilization program is carried out according to pasteurization.

[0177] Borneol and menthol cannot be prepared by liquefaction as single ingredients and can only be prepared in a compound form.

[0178] Example 15: Compound two-step process. Dry vibration mill + continuous wet vibration mill

[0179] Ginseng, Ophiopogon japonicus, Schisandra chinensis, and xylitol (Shengmai liquid preparation) were ground into a dry vibration mill at a ratio of 1:2:1:2 until the particle size was 300 mesh (95%) finer than 95%. Nitrogen was introduced into the grinding process. The dry powder was transferred to a powder-liquid mixer, mixed at a solid-water ratio of 1:2, and then pumped to a continuous wet vibration mill until the particle size was d 50 The discharge is less than 13 microns, and then it is sterilized in series with ultra-high temperature instantaneous sterilization (UHT) at 135℃ for 5 seconds, and filled according to the aseptic cold filling plan.

[0180] Example 16: Compound two-step process. Dry vibration mill + continuous vibration mill

[0181] According to the prescription of Liuwei Dihuang Fang (160g of cooked rehmannia root, 80g of cornus officinalis, 60g of peony bark, 80g of yam, 60g of poria, 60g of oriental rhizome), 100kg of the mixture was dry-grinded to 95% of -300 mesh, 300kg of water was added and mixed, and then the mixture was continuously pumped to the vibration mill for wet grinding. The mixture was circulated back and forth between the mill and the material tank for 3 times until d 50 Discharged particles smaller than 28 microns can be subsequently sterilized in series with ultra-high temperature (UHT) sterilization and bagged according to aseptic cold filling protocols. Alternatively, the material can be bagged and sterilized after grinding, following the pasteurization protocol.

[0182] Example 17: Compound two-step process. Dry vibration mill + continuous wet vibration mill

[0183] Taking Yangyin Qingfei Pills (200g Rehmannia root, 120g Radix Ophiopogonis, 160g Scrophulariae, 80g Fritillaria cirrhosa, 80g White Peony Root, 80g Paeonia lactiflora, 50g Mentha, 40g Licorice) as an example, the medicinal materials were cleaned, dried and sterilized, and then vibrated dry-grinded to 300 mesh or 95% fineness according to the prescribed ratio. Nitrogen was added during the grinding process. The dry powder was transferred to a powder-liquid mixer and mixed at a solid-water ratio of 1:2. After being sent to a continuous wet vibration mill for grinding, the powder was then ground to d 50 The output is less than 31 microns and can be subsequently sterilized in series with ultra-high temperature (UHT) and filled according to the aseptic cold filling method.

[0184] The conventional method of making honey pills for Yangyin Qingfei Pills is difficult because they are too sticky and require old honey to form pills. However, the pills are often too hard and have poor compliance. The technical solution of the present invention can effectively solve this problem, with a smooth taste and no need to add auxiliary materials.

[0185] Example 18: Two-step process. Dry vibration milling + wet vibration milling

[0186] 6kg of Radix Aconiti Lateralis Preparata, 4kg of dried ginger, and 6kg of roasted licorice root (Sini Decoction) were selected and removed, and dried at 55℃ for 6-20h to make the moisture content of the three raw materials ≤7%. After drying, the materials were put into dry vibration mill for 15min to make the fine powder 300 mesh screening rate reach more than 95%. The obtained mixed fine powder was transferred to powder-liquid mixer, added with 32kg of pure water and mixed, and then put into wet vibration mill for 10min to d 50 The material is discharged when the particles are smaller than 33 microns and is sterilized at 85℃ for 30 minutes after bagging.

[0187] Example 19: Two-step process, dry rotor grinding + continuous vibration mill

[0188] 0.9kg of donkey hide gelatin was cut into small pieces less than 5mm, 3kg of jujube was dried at 60℃ for 48h, and 3kg of astragalus was dried at 60℃ for 8h. After the treatment, the moisture content of the three raw materials was ≤8%. The dried materials were crushed by rotor mill for 20min, so that the passing rate of the obtained fine powder on 120 mesh sieve reached more than 95%. 20.7kg of pure water was added to the mixed fine powder and mixed evenly, and then it was continuously pumped to wet vibration grinding, and circulated back and forth between the mill and the material tank for 3 times until d 50 The material is discharged if the particle size is less than 28 microns, and then packed in bags and sterilized at 85℃ for 30 minutes.

[0189] Example 20

[0190] According to the prescription of Sanhuang Tablets (300g of rhubarb, 5g of berberine hydrochloride, and 21g of scutellaria baicalensis extract), a total of 100kg was taken, and the rhubarb and berberine hydrochloride were crushed to 95% of -300 mesh by dry vibration mill, and 300kg of scutellaria baicalensis extract was added and mixed. After that, the mixture was continuously pumped to the vibration mill for wet grinding until the d50 was less than 26 microns. After grinding, the material was bagged and sterilized. The sterilization plan was carried out according to pasteurization.

[0191] The invention of the present application can be applied to the preparation of liquefied Chinese medicines such as Guifu Dihuang, Huoxiang Zhengqi, Baohe Pills, Guizhi Fuling, Tongxuan Lifei, Juhong Pills, Fuzi Lizhong, Xiaoyao Pills, Shenling Baizhu, Shugan Hewei, Qingyin Pills, Yupingfeng, Buzhong Yiqi, etc.

[0192] Example 21

[0193] The prepared American ginseng and longan single-ingredient liquefied Chinese medicines are mixed according to the ratio of 1:10 of the original medicinal materials, mixed evenly and filled into small bags, and then sterilized to obtain the finished product.

[0194] Example 22

[0195] According to the prescription of Sanhuang Tablets (300g of rhubarb, 5g of berberine hydrochloride, and 21g of scutellaria baicalensis extract), a total of 100kg was taken, and the rhubarb, berberine hydrochloride, and scutellaria baicalensis extract were ground to 95% of -300 mesh by dry vibration mill, and then 100kg of honey and 300kg of water were added and mixed. The mixture was then continuously pumped to a vibration mill for wet grinding until the d50 was less than 26 microns. After grinding, the material was bagged and sterilized. The sterilization plan was carried out according to pasteurization.

[0196] Example 23

[0197] According to the prescription of Sanhuang Tablets (300g of rhubarb, 5g of berberine hydrochloride, and 21g of scutellaria baicalensis extract), a total of 100kg was taken, and rhubarb, berberine hydrochloride, and scutellaria baicalensis extract were added with 30kg of white sugar, and ground into -300 mesh 95% by dry vibration mill, mixed with 300kg of water, and then continuously pumped to a vibration mill for wet grinding until d50 was less than 26 microns. After grinding, the material was bagged and sterilized. The sterilization plan was carried out according to pasteurization.

[0198] Preparation of liquefied Chinese medicine pastes

[0199] Example 24: Two-step process: dry vibration milling + continuous wet vibration milling

[0200] Yuling Paste (21 parts American ginseng and 210 parts longan) is cleaned, dried, and sterilized according to the formulated ratio. It is then dry-ground in a vibrating mill to 95% 300-mesh size, with nitrogen purging throughout the grinding process. The dry powder is then transferred to a powder-liquid mixer, mixed at a solid-to-water ratio of 1:3, and continuously pumped through a steam ejector at 150°C for 5 seconds. It is then cooled to 50°C in a vacuum unit and then piped to 30°C before being wet-ground in a vibrating mill and filled according to the aseptic cold filling protocol. Prior to formal production, the production pipeline and in-line equipment are sterilized, and production begins after sterilization is complete.

[0201] Appearance properties: gray-brown, good gloss, no granularity, almost no flow, no dispersion and juice separation, no impurities; viscosity test: no dripping within 8 seconds.

[0202] Stirring viscometer test:

[0203] Laser particle size diffractometer particle size detection:

[0204] Microbiological testing:

[0205] Examples of paste prescriptions that can be prepared using the method of this application are as follows:

[0206] In the Chinese Pharmacopoeia, such as Erdong Paste, Shandong Donkey-hide Gelatin Paste, Chuanbei Snow Pear Paste, Guilu Erxian Paste, Donkey-hide Gelatin Three Treasures Paste, Donkey-hide Gelatin Blood-Replenishing Paste, Loquat Leaf Paste, Gastrointestinal Recovery Paste, Compound Yunnan Millettia Paste, Yangxin Dingjin Paste, Yangyin Qingfei Paste, Prunella Vulgaris Paste, Motherwort Paste, Yifei Qinghua Paste, Astragalus Stomach-Strengthening Paste, Silver Psoriasis Paste, Tianjing Bushen Paste, Qiangli Loquat Paste (Honey Refined), Liangyi Paste, etc., can all be achieved by adopting the present invention.

[0207] (II) Comparative study on the material basis of liquefied Chinese medicine and traditional decoctions

[0208] To investigate whether the material basis of liquefied slices differs from that of traditional decoctions (standard decoctions, i.e., extracts), a study using Astragalus membranaceus as an example was conducted. The content, transfer rate, and extract content of the active (or index) ingredients in Astragalus membranaceus slices, astragaloside IV and calycosin glucoside, were compared between traditional decoctions and liquefied slices. The results showed that the extract content was higher in liquefied slices, which correlated with the transfer rate of the index ingredients (see the table below).

[0209] Content and transfer rate of index components in liquefied slices of Astragalus membranaceus and traditional decoction

[0210] Content of extracts from traditional decoctions and liquefied slices of Astragalus membranaceus

[0211] To investigate the impact of the processing technology of liquefied slices on the stability of their material base, the characteristic spectra of the liquefied slices and the original slices were examined. By identifying characteristic peaks and searching for differential markers, the aim is to provide a reference for the quality control and evaluation of liquefied slices of traditional Chinese medicine. The following two figures show the characteristic spectra of the liquefied slices of Astragalus and the original slices collected using different liquid chromatography detectors. Three of the components were identified using reference substances: calycosin isoflavone glucoside, calycosin isoflavone, and astragaloside II. The number of characteristic peaks and peak retention times were compared, indicating that the liquefied slices were consistent with the original slices. See Figures 1-2.

[0212] Based on this, we compared the characteristic spectra of 11 other liquefied medicinal pieces—roasted licorice root, ginger, ginseng, raw rehmannia root, cinnamon twig, jujube, cornus fruit, polygonum multiflorum, cyathula root, Scrophularia ningpoensis, and oriental rhizome—with those of the original pieces. The number and positions of characteristic peaks were consistent with those of the original pieces, and no other characteristic peaks were observed. This indicates that the production process of the liquefied medicinal pieces did not cause any changes in the material basis. See Figures 3-13.

[0213] (III) Comparative study on the pharmacodynamics of liquefied medicinal pieces and traditional decoctions

[0214] To provide pharmacological research evidence for dose conversion between liquefied medicinal slices and traditional decoctions, we conducted a comparative study on the efficacy of two liquefied medicinal slices, Astragalus membranaceus and Arctium lappa, and traditional decoctions. The results showed that in the cyclophosphamide-induced immunodeficiency model of mice, Astragalus membranaceus liquefied medicinal slices had an immune-enhancing effect that was equal to or even superior to that of traditional decoctions when the dose converted to 3 / 5 times the total extract was compared with that of traditional decoctions; in the LPS fever model, Arctium lappa liquefied medicinal slices had an antipyretic effect that was equal to or even superior to that of traditional decoctions when the dose converted to 1 / 2 times the total extract was compared with that of traditional decoctions.

[0215] (IV) Comparative study on the pharmacokinetics of liquefied herbal medicine slices and traditional decoctions

[0216] To investigate the pharmacokinetic characteristics of oral administration of liquefied slices, we conducted a comparative pharmacokinetic study in rats of two liquefied slices of Astragalus and Arctium lappa, and traditional decoctions. The results showed that at clinically equivalent doses, the relative bioavailability of calycosin glucoside and cycloastragenol increased in rats administered with liquefied slices of Astragalus; at high doses, the relative bioavailability of cycloastragenol and astragaloside IV increased (see Figure 3). Oral administration of liquefied slices of Arctium lappa increased the relative bioavailability of arctiin in rats, and the time to peak arctiin concentration was shortened after liquefaction, indicating faster absorption in vivo (see Figure 4).

[0217] (V) Comparative study on acute toxicity of liquefied medicinal pieces and traditional decoctions

[0218] To understand the safety of liquefied herbal slices compared with traditional decoctions, we conducted a comparative acute toxicity study in mice using two liquefied herbal slices, Astragalus and Arctium lappa, and traditional decoctions. The maximum feasible dose (MFD) method was used for determination. The results showed that liquefied herbal slices did not increase the safety risk compared with traditional decoctions (see the table below).

[0219] Comparative study results on the acute toxicity of Astragalus and Burdock Fruit liquefied slices and traditional decoctions in mice

[0220] (VI) Comparison between the liquefied Chinese medicine of this application and traditional preparations

[0221] 1. Comparison between liquefied Chinese medicine and micro-pulverized Chinese medicine

[0222] The varieties of Chinese medicine formula granules that use ultrafine grinding technology include: fried chicken gizzard lining, golden sand cattle, antelope horn, Ganoderma lucidum, pollen pollen, indigo, scorpion, Panax notoginseng, gypsum, buffalo horn, leech, sandalwood, Gastrodia elata, centipede, American ginseng, dragon's blood, Zhejiang Fritillary bulb, placenta, cicada shell, agarwood, Sichuan Fritillary bulb, roasted pangolin, sea gold sand, amber, etc.

[0223] There is an essential difference between crushing and extracting medicine, and the two methods of preparation are completely different for raw use and decoction use. There are many unreasonable applications in the traditional granular or micro-powdered medicine mode. The following is a comparative study of the liquefied Chinese medicine and the micro-powdered Chinese medicine of the present invention:

[0224] 2. Comparison between liquefied Chinese medicine and traditional large honey pills, small honey pills, water pills, powders, capsules, tablets, granules, and oral liquids

[0225] (VII) Summary of the characteristics of the liquefied Chinese medicine of this application

[0226] This application is applicable to various medicinal materials, such as:

[0227] The beneficial effects of this application:

[0228] 1. Compared with the simplest liquefaction operation, which involves simply adding water to a fine powder, the liquefied Chinese medicine of the present invention exhibits stable properties and does not separate into separate layers. The liquid (paste or slurry) retains its original color and avoids oxidative browning. Furthermore, after dilution 1000 times, it becomes translucent.

[0229] 2. The preparation process of the present invention eliminates waste residue caused by varying degrees of pulverization difficulty, eliminates the need for classification, and avoids oxidation, browning, enzyme reactions, and microbial reactions, thereby maintaining the original flavor of the Chinese medicine. The material basis remains unchanged after liquefaction. Low-temperature, fully sealed processing can also be used to avoid loss of volatiles.

[0230] 3. It has a bright and delicate surface, good fluidity when squeezed, and a smooth taste. Compared with decoctions, it not only saves medicinal materials but also improves compliance. It has a fast onset of effect and is a beneficial supplement to the existing Chinese medicine decoction system.

[0231] 4. The equipment material does not pollute the materials.

[0232] 5. Low cost, high solubility, no extraction required, small amount of medicinal materials used, full utilization of effective ingredients, original flavor, and no drug residue, reducing pollution and waste.

[0233] 6. Freeze-thaw resistance: After four freeze-thaw cycles, the properties remained largely unchanged. This is likely due to the fiber's effective water retention and the hemicellulose's ability to lower the freezing point. This characteristic helps mitigate the adverse effects of high temperatures and temperature fluctuations during transoceanic shipping, and facilitates long-term storage.

[0234] 7. The finished product has high solid content and the drug volume and weight are small.

[0235] The present invention replaces the traditional water decoction and heating method to release and transfer ingredients by achieving high-density energy transfer and material transfer, thereby solving the existing barriers to material and energy transfer. This technology uses mechanical energy to break through the barrier between the interface of the particle cluster and the particles, thereby forming multiple single particles. The surface energy of a single solvent is used to isolate the single particles so that they cannot contact the interface of the original particle cluster. Kinetic energy is used to force the single particles to intervene in the solvent, achieving non-similar dissolution and efficient liquefaction of all ingredients. When the insoluble solids reach a sufficient fineness and the water content is as low as possible, the fibers of the medicinal materials or decoction pieces themselves are used as stabilizer auxiliary materials to achieve a highly stable state in water, which is not limited by the variety of Chinese medicinal materials.

[0236] The present invention provides a new form of traditional Chinese medicine. The liquefied traditional Chinese medicine of the present invention not only improves the yield and has multiple components, thereby improving oral bioavailability, but also reduces production costs and can be combined with temperature control, anti-oxidation and other functions to form an innovative liquefaction system.

Claims

1. A liquefied Chinese medicine, characterized in that: The liquefied Chinese medicine is composed of all ingredients of Chinese medicinal materials or decoction pieces, water and optional carriers or excipients, and has a viscosity within the range of 6000-500000 cp.

2. The liquefied Chinese medicine according to claim 1, characterized in that: The Chinese medicinal materials are selected from animal, plant or mineral Chinese medicinal materials, excluding fresh berries.

3. The liquefied Chinese medicine according to claim 1 or 2, characterized in that: The viscosity of the liquefied Chinese medicine is 10000-330000 cp, or 13000-180000 cp.

4. The liquefied Chinese medicine according to any one of claims 1 to 3, characterized in that: The cells of the animal and plant Chinese medicinal materials are in a broken cell state, and the cell breaking rate is more than 80%.

5. The liquefied Chinese medicine according to claim 4, characterized in that: The cell wall breaking rate of the animal and plant Chinese medicinal materials is above 95%.

6. The liquefied Chinese medicine according to any one of claims 1 to 5, wherein the Chinese medicinal materials or decoction pieces are single prescriptions or compound prescriptions.

7. The method for preparing the liquefied Chinese medicine according to any one of claims 1 to 6, characterized in that: The preparation method comprises a wet grinding step of grinding Chinese medicinal materials or decoction pieces, water and optional water-containing substances.

8. The preparation method according to claim 7, wherein when the water-containing substance is a water extract, the added water-containing substance partially replaces or completely replaces the added water, and ensures that water is the continuous phase.

9. The preparation method according to claim 7 or 8, characterized in that: The method further comprises a dry grinding step, which precedes the wet grinding step.

10. The preparation method according to any one of claims 7 to 9, characterized in that: The wet grinding is wet vibration grinding.

11. The preparation method according to any one of claims 7 to 10, characterized in that: In wet grinding, the total amount of Chinese medicinal materials or decoction pieces and water is in a solid-to-water ratio of 1:1 to 1:10 by weight, such as 1:1 to 1:5, 1:2 to 1:

3.

12. The preparation method according to any one of claims 7 to 11, characterized in that: In the preparation method, the Chinese medicinal materials or decoction pieces do not need to be graded according to particle size.

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