CN118027010A - Process for producing silymarin with high dissolution rate - Google Patents
Process for producing silymarin with high dissolution rate Download PDFInfo
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- CN118027010A CN118027010A CN202410180602.3A CN202410180602A CN118027010A CN 118027010 A CN118027010 A CN 118027010A CN 202410180602 A CN202410180602 A CN 202410180602A CN 118027010 A CN118027010 A CN 118027010A
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- silymarin
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- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 229960004245 silymarin Drugs 0.000 title claims abstract description 65
- 235000017700 silymarin Nutrition 0.000 title claims abstract description 65
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 title claims abstract description 64
- 238000004090 dissolution Methods 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims abstract description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000008213 purified water Substances 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000000463 material Substances 0.000 claims abstract description 6
- 239000012065 filter cake Substances 0.000 claims description 44
- 238000001035 drying Methods 0.000 claims description 38
- 239000006185 dispersion Substances 0.000 claims description 22
- 239000002245 particle Substances 0.000 claims description 20
- 239000002244 precipitate Substances 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 9
- 238000001704 evaporation Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 230000008020 evaporation Effects 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 239000013049 sediment Substances 0.000 claims description 7
- 238000004806 packaging method and process Methods 0.000 claims description 6
- 244000272459 Silybum marianum Species 0.000 claims description 5
- 239000012141 concentrate Substances 0.000 claims description 5
- 238000000227 grinding Methods 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 238000007689 inspection Methods 0.000 claims description 4
- 241000196324 Embryophyta Species 0.000 claims description 3
- 235000010841 Silybum marianum Nutrition 0.000 claims description 3
- 238000009825 accumulation Methods 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 235000013399 edible fruits Nutrition 0.000 claims description 3
- 238000003860 storage Methods 0.000 claims description 3
- 238000007796 conventional method Methods 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 239000011812 mixed powder Substances 0.000 claims description 2
- 238000013021 overheating Methods 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 230000004580 weight loss Effects 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 238000011084 recovery Methods 0.000 abstract description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 6
- 239000007962 solid dispersion Substances 0.000 description 5
- 239000001116 FEMA 4028 Substances 0.000 description 4
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 4
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 4
- 229960004853 betadex Drugs 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 238000004513 sizing Methods 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
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- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 229940044519 poloxamer 188 Drugs 0.000 description 2
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- 230000007928 solubilization Effects 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 239000008118 PEG 6000 Substances 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
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- 239000002552 dosage form Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
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- 238000001727 in vivo Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- -1 silymarin compound Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of silymarin, and provides a production process of silymarin with high dissolution rate, which comprises the steps of adding no other auxiliary materials in the production process, and has low production cost, no influence on the content and other indexes of the silymarin as raw material medicines, no damage to the molecular structure of any component in the silymarin, and ethanol used in the production process belongs to three solvents which are acceptable solvents for people, so that the residues of acetone, n-hexane, ethyl acetate and the like are reduced. Because the purified water is used in the production process, and the silymarin is insoluble in water, the production operation is carried out at low temperature, and the recovery rate is as high as more than 85 percent. The equipment investment is less, the high-dissolution silymarin can be produced on the basis of the original silymarin production equipment, the production cost is low, the dissolution rate is greatly improved from about 40 percent to 90+/-5 percent. By the technical scheme, the problems of low dissolution and low availability in the prior art are solved.
Description
Technical Field
The invention relates to the technical field of silymarin, in particular to a production process of silymarin with high dissolution rate.
Background
At present, silymarin is indissolvable in water and common organic solvents, and has poor oral absorption, so that the bioavailability is low, thereby influencing the clinical curative effect, and a great deal of work is done by pharmaceutical workers at home and abroad for improving the bioavailability, and the measures for improving the absorption of indissolvable drugs generally comprise superfine grinding, salifying, adding a cosolvent and the like, and in recent years, methods for preparing cyclodextrin inclusion compounds, solid dispersions, synthesizing phospholipid complexes, preparing different dosage forms and the like are adopted. Studies have shown that the dissolution and bioavailability have been greatly improved by these methods.
In the prior art:
1. Complexing to form salt and forming ester: at present, the compound preparation of silymarin is actively developed at home and abroad to improve the oral bioavailability, increase the curative effect and expand the application range, such as silybin-meglumine salt in 80 s in China, silymarin compound preparation developed at home and abroad, silymarin-phthalate monoester sodium salt, silybin-cyclodextrin silybin-phosphatidylcholine compound salt and the like.
2. Preparation-solid dispersion technique
In the research on the human body bioavailability of the silymarin solid dispersion, the silymarin accords with a first-level absorption two-chamber model in vivo, and the bioavailability of the capsule is higher than that of the tablet.
A series of research and study on the silymarin shows that the dissolution rate can be obviously improved by polyethylene glycol (PEG) melt, polyvinylpyrrolidone (PVP) coprecipitate and beta-cyclodextrin (beta-CD) inclusion compound, and the dissolution rate can also be improved by directly tabletting after grinding with compressible starch, microcrystalline fiber and beta-CD; compared with a plurality of auxiliary materials such as urea, PVP, poloxamer 188 and the like which are taken as carriers, the dissolution rate in the poloxamer 188 carrier is found to be the largest and the dissolution is the fastest; the solubilization effects of PVP, PEG-6000 solid dispersion, beta-CD inclusion compound and the like are compared, and the solubilization effect is considered to be good because the drug-loading capacity taking PVPK30 as a carrier is large;
zhu et al studied the dissolution rate of silymarin solid dispersion and considered that the dissolution rate was optimal with silymarin to PEG ratio of 1:9, with the maximum cumulative dissolution rate being 64.27%.
Disclosure of Invention
The invention provides a production process of silymarin with high dissolution rate, which solves the problems of low dissolution rate and low bioavailability in the related technology.
The technical scheme of the invention is as follows: a production process of silymarin with high dissolution rate comprises the following steps:
step S1: silymarin is dissolved in 5-10 times of ethanol and heated to 75-85 ℃ for dissolution;
step S2: recovering and concentrating the solution of silymarin and ethanol to 5-8 times of the solution;
step S3: pouring the concentrated solution into 80-100 times of purified water, stirring and dispersing to form hydroalcoholic dispersion;
Step S4: standing the hydroalcoholic dispersion to form a water layer and a precipitation layer, and discarding the water layer;
Step S5: centrifuging the precipitate layer of the dispersion;
Step S6: after finishing the filter cake, drying at 50+/-5 ℃, and detecting that the drying loss is less than 5%;
Step S7: crushing and mixing the dried filter cake by using an ultrafine crusher, and checking an intermediate;
Step S8: and packaging the qualified finished product.
As a preferable scheme of the invention, in the S1, silymarin is dissolved in 5-10 times of ethanol and heated and dissolved at 75-85 ℃, and the specific steps are as follows:
(1) The silymarin raw material is extracted from dry and impurity-free silybum marianum plant material such as silybum marianum seeds or fruits by using proper solvents such as acetone, ethyl acetate, ethanol and the like.
(2) Pulverizing the extracted silymarin into granule or powder with proper size.
(3) The silymarin is extracted by a conventional method by taking ethanol, acetone or ethyl acetate as an extraction solvent, so that the quality and purity of the solvent are ensured.
(4) According to the requirement, the volume of the ethanol is 5-10 times of the weight of the silymarin so as to fully dissolve the silymarin.
In a preferred embodiment of the present invention, in S2, the solution of silymarin and ethanol is recovered and concentrated to 5 to 8 times, and the specific steps are as follows:
(1) Placing the solution of silymarin and ethanol into evaporator such as concentrating tank, heating to appropriate temperature, and evaporating ethanol.
(2) In the evaporation process, the temperature is controlled to avoid too high or too low, the too high temperature may cause the bumping or silymarin degradation, and the too low temperature may cause the ethanol to be completely evaporated.
(3) The volume of the concentrate is measured and if 5 to 8 times the volume is reached, the operation may be stopped, if the target volume is not reached, and the evaporation and condensation operations may be continued until the desired volume is reached.
(4) The concentrate is kept in a suitable container and ensures that it remains stable during transport and storage.
In a preferred embodiment of the present invention, in S3, the concentrated solution is poured into 80-100 times of purified water and stirred to form a hydroalcoholic dispersion, and the specific steps are as follows:
(1) According to the volume of the concentrated solution, preparing water with the volume 80-100 times of the weight of silymarin, pouring the prepared purified water into the concentrated solution, and stirring while chamfering to ensure uniform mixing.
(2) After pouring water, the concentrate and water are continuously stirred to be fully dispersed to form hydroalcoholic dispersion.
In a preferred embodiment of the present invention, in S4, the aqueous-alcoholic dispersion is allowed to stand to form an aqueous layer and a precipitate layer, and the aqueous layer supernatant is discarded, specifically comprising the steps of:
(1) Placing the hydroalcoholic dispersion in a container, standing for a period of time to allow the water layer and the precipitate layer to delaminate naturally.
(2) The upper aqueous layer is carefully sucked or poured out using a suction tube, suction ball or other suction means, taking care not to disturb the bottom sediment layer to maintain its stability.
(3) The removed aqueous layer was discarded.
In a preferred embodiment of the present invention, in S5, the step of centrifuging the precipitate layer of the dispersion liquid comprises the following specific steps:
(1) The proper centrifugal equipment is selected to clean it up, ensuring no residue.
(2) The precipitate layer of the dispersion is carefully introduced into a filter centrifuge with stirring and the precipitate is slowly added to ensure that the precipitate is in place in the centrifuge, avoiding overflow or too little.
(3) Setting proper centrifugal time and rotating speed according to the operation description of the centrifugal machine, starting the centrifugal machine, observing that no filtrate is left after the centrifugal operation is finished, and taking out sediment.
In a preferred embodiment of the present invention, in S6, after the filter cake is granulated, the filter cake is dried at 50±5 ℃, and the weight loss on drying is detected to be less than 5%, and the specific steps are as follows:
(1) And (3) finishing the filter cake obtained by centrifugation to ensure that the particle size is uniform and no obvious large blocks or particles exist, and finishing the particles by using proper crushing or grinding equipment.
(2) Placing the granulated filter cake particles on heating equipment, ensuring that the temperature of the filter cake particles can be adjusted and kept at 50+/-5 ℃, checking whether the equipment is clean and dry, and ensuring no residues.
(3) Placing the granulated filter cake particles into a drying device, ensuring uniform placement, avoiding accumulation or overlapping, setting the temperature of the drying device at 50+/-5 ℃, keeping the constant temperature, starting the drying device, and starting the drying treatment of the filter cake.
(4) And after the filter cake reaches the required drying degree, detecting the drying weight, weighing the weight of the filter cake before drying and the weight of the filter cake after drying, and calculating the difference value of the two to obtain the drying weight, thereby ensuring the drying weight to be below 5%.
In a preferred embodiment of the present invention, in S7, the dried filter cake is crushed by a micro-crusher or a super-micro-crusher, and then mixed by a mixer, and then an intermediate test is performed, which specifically comprises the following steps:
(1) And (3) putting the dried filter cake into a feeding container of a micronizer, starting the micronizer, and carrying out crushing operation, wherein in the crushing process, attention is paid to observing the crushing condition, so that the dried filter cake is uniformly crushed, and no caking or overheating phenomenon exists.
(2) And (3) performing intermediate inspection on the mixed powder to ensure that the quality of the powder meets the expected requirements.
In S8, the specific steps of the qualified finished product package are as follows:
(1) And placing qualified products into a packaging container to ensure accurate quantity without redundant or insufficient quantity.
(2) The packaging container is sealed well, so that the product is ensured not to leak or be polluted.
The working principle and the beneficial effects of the invention are as follows:
1. In the production process, other auxiliary materials are not needed to be added, the production cost is low, the content and other indexes of the silymarin are not influenced as raw material medicines, the molecular structure of any component is not damaged, in addition, ethanol used in the production process belongs to three solvents which are acceptable to people, the residues of acetone, n-hexane, ethyl acetate and the like are reduced, purified water is used in the production process, the purified water can be repeatedly utilized, the environment is not polluted, the product yield is high, the silymarin is not dissolved in water and is precipitated at low temperature, the recovery rate is up to more than 85%, the equipment investment is less, the high-dissolution silymarin can be produced on the basis of the original silymarin production equipment, the production cost is low, the dissolution rate is improved greatly, and the dissolution rate is directly improved by 90+/-5% from about 40%.
Drawings
The invention will be described in further detail with reference to the drawings and the detailed description.
FIG. 1 is a flow chart of the present invention.
Detailed Description
The technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by one of ordinary skill in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
Selecting dry and impurity-free silybum marianum plant raw materials, such as silybum marianum seeds or fruits, crushing the plant raw materials into particles with proper size after oil extraction, selecting ethanol, acetone, ethyl acetate and the like as extraction solvents, extracting silymarin, ensuring the quality and purity of the solvents, dissolving silymarin by ethanol according to the needs, taking ethanol with the weight of 5-10 times of the silymarin to fully dissolve the silymarin, putting the silymarin and ethanol solution into an evaporator to be heated to proper temperature to evaporate the ethanol, controlling the temperature in the evaporation process to avoid excessively high or excessively low temperature which may cause degradation of the silymarin, and excessively low temperature which may cause complete evaporation of the ethanol, measuring the volume of concentrated solution, stopping the operation if 5-8 times of the concentrated solution is reached, if the target amount is not reached, continuing the evaporation and condensation operation, until reaching the required volume, storing the concentrated solution in a proper container, ensuring that the concentrated solution is kept stable in the transportation and storage processes, preparing 80-100 times of water quantity according to the volume of the concentrated solution, pouring the prepared purified water into the concentrated solution, taking care of stirring while reversing to ensure uniform mixing, after pouring the water, dispersing and separating out ethanol solution in the purified water, namely dissolving silymarin in ethanol to form supersaturated solution, quickly separating out the supersaturated solution into amorphous powder in the purified water, continuously stirring the concentrated solution and the water to ensure that the concentrated solution and the water are fully dispersed to form hydroalcoholic dispersion, placing the hydroalcoholic dispersion in the container, standing for a period of time to ensure that a water layer and a precipitation layer are naturally layered, carefully sucking or pouring out an upper water layer by using a suction pipe or a suction ball, taking care of not disturbing the precipitation layer at the bottom to keep the stability, discarding the water layer, selecting proper centrifugal equipment, cleaning the water layer, ensuring no residue, carefully introducing the precipitate layer of the dispersion liquid into the centrifugal equipment, putting the centrifugal tube filled with the dispersion liquid into a centrifugal machine, ensuring the proper placement position, avoiding inclination or sliding, setting proper centrifugal time and rotating speed according to the operation instruction of the centrifugal machine, starting the centrifugal machine, and taking out a centrifugal filter cake after the centrifugal operation is completed.
Further, the filter cake obtained by centrifugation is subjected to particle sizing treatment, so that the particle size is uniform, no obvious large blocks or particles are left, proper crushing or grinding equipment can be used for particle sizing, the filter cake after particle sizing is placed on heating equipment, the temperature cannot exceed 55 ℃ in the re-drying process, otherwise silymarin can be remelted to form partial crystals, the dissolution degree returns to the original point, the temperature of the silymarin can be regulated and kept at 50+/-5 ℃, the inspection equipment is clean and dried, no residues are ensured, the filter cake after particle sizing is placed in drying equipment, the uniform placement is ensured, the accumulation or overlapping is avoided, the temperature of the drying equipment is set at 50+/-5 ℃, the constant temperature is kept, the drying equipment is started, the drying treatment is started, after the filter cake reaches the required drying degree, the detection of drying loss, the weight of the filter cake before drying and the weight of the filter cake after drying are weighed, the difference value of the filter cake is calculated, namely the drying loss is the drying loss, the filter cake is ensured to be lower than 5%, the filter cake after the drying loss is placed in a feeder of a machine or an ultrafine pulverizer, the pulverizer is started, the pulverizer is crushed, the pulverizer is subjected to crushing operation, the filter cake is observed to be free of residues, the dissolution loss is ensured, the filter cake is not to be uniform, the dissolution loss is ensured to be formed, the dissolution loss is not equal to the expected, the dissolution of the solution is ensured, the filter cake is not to be packaged, the dissolution is ensured to be uniform, the dissolution loss is not required to be formed, the solution is not equal to be packaged, the dissolution is ensured, the filter cake is not required to be packaged, the dissolution is not is ensured, the dissolution is not is required to be uniform, and the filter is packaged, and the filter cake is not required to be packaged, and the filter is packaged, and the quality is not required to be dissolved, and is packaged or is different, the invention also adopts a superfine pulverizer to pulverize, basically reaches the fineness of 200-300 meshes, and the two technologies are used together.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (9)
1. The production process of the silymarin with high dissolution rate is characterized by comprising the following steps of:
step S1: silymarin is dissolved in 5-10 times of ethanol and heated to 75-85 ℃ for dissolution;
step S2: recovering and concentrating the solution of silymarin and ethanol to 5-8 times of the solution;
Step S3: pouring 80-100 times of purified water into the concentrated solution, and stirring and dispersing to form hydroalcoholic dispersion;
Step S4: standing the hydroalcoholic dispersion to form a water layer and a precipitation layer, and discarding the water layer;
Step S5: centrifuging the precipitate layer of the dispersion;
Step S6: after finishing the filter cake, drying at 50+/-5 ℃, and detecting that the drying loss is less than 5%;
step S7: crushing and mixing the dried filter cake by using a superfine pulverizer, and checking an intermediate;
Step S8: and packaging the qualified finished product.
2. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S1, silymarin is dissolved in 5-10 times of ethanol at 75-85 ℃ and heated for dissolution, and the specific steps are as follows:
(1) Selecting dry and impurity-free silymarin plant material such as seed or fruit of Silybum marianum.
(2) Plant material is broken into particles or powder of suitable size.
(3) The silymarin is extracted by a conventional method by taking ethanol, acetone or ethyl acetate as an extraction solvent, so that the quality and purity of the solvent are ensured.
(4) According to the requirement, the silymarin is fully dissolved by ethanol with the quantity (mass: volume) of 5-10 times of the silymarin.
3. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S2, the solution of silymarin and ethanol is recovered and concentrated to 5-8 times, and the specific steps are as follows:
(1) The solution of silymarin and ethanol is put into an evaporator and heated to a proper temperature to evaporate the ethanol.
(2) In the evaporation process, the temperature is controlled to avoid too high or too low, the silymarin is degraded due to the too high temperature, and the ethanol is not completely evaporated due to the too low temperature.
(3) The volume of the concentrate is measured and if 5 to 8 times the volume is reached, the operation may be stopped, if the target volume is not reached, and the evaporation and condensation operations may be continued until the desired volume is reached.
(4) The concentrate is kept in a suitable container and ensures that it remains stable during transport and storage.
4. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S3, the concentrated solution is poured into 80-100 times of purified water and stirred and dispersed to form a hydroalcoholic dispersion, and the specific steps are as follows:
(1) According to the volume of the concentrated solution, 80-100 times of purified water is prepared, and the concentrated solution is slowly poured into the prepared purified water, and the solution is stirred while being inverted to ensure uniform mixing.
(2) After pouring water, stirring is continued to fully disperse the mixture to form a hydroalcoholic dispersion.
5. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S4, the aqueous layer and the precipitate layer are formed after the aqueous-alcoholic dispersion is left to stand, and the supernatant liquid of the aqueous layer is discarded, specifically comprising the steps of:
(1) Placing the hydroalcoholic dispersion in a container, standing for a period of time to allow the water layer and the precipitate layer to delaminate naturally.
(2) The upper aqueous layer is carefully sucked or poured out using a suction tube, suction ball or other suction means, taking care not to disturb the bottom sediment layer to maintain its stability.
(3) The removed clear aqueous layer was discarded.
6. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S5, the precipitation layer of the dispersion is centrifuged, comprising the following specific steps:
(1) The proper centrifugal equipment (optionally a filter centrifuge) is selected and cleaned to ensure that no residue is present.
(2) The sediment layer of the dispersion liquid is led into a filtering centrifuge under the stirring condition, and the sediment liquid is slowly added, so that the sediment liquid is ensured to be at a proper position in the centrifuge, and overflow or too little is avoided.
(3) Setting proper centrifugal time and rotating speed according to the operation description of the centrifugal machine, starting the centrifugal machine, observing that no filtrate is left after the centrifugal operation is finished, and taking out sediment.
7. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S6, the filter cake is dried at 50±5 ℃ after finishing, and the weight loss on drying is detected to be less than 5%, and the specific steps are as follows:
(1) And (3) finishing the filter cake obtained by centrifugation to ensure that the particle size is uniform and no obvious large blocks or particles exist, and finishing the particles by using proper crushing or grinding equipment.
(2) Placing the granulated filter cake particles on heating equipment, ensuring that the temperature of the filter cake particles can be adjusted and kept at 50+/-5 ℃, checking whether the equipment is clean and dry, and ensuring no residues.
(3) Placing the granulated filter cake particles into a drying device, ensuring uniform placement, avoiding accumulation or overlapping, setting the temperature of the drying device at 50+/-5 ℃, keeping the constant temperature, starting the drying device, and starting the drying treatment of the filter cake.
(4) And after the filter cake reaches the required drying degree, detecting the drying weight, weighing the weight of the filter cake before drying and the weight of the filter cake after drying, and calculating the difference value of the two to obtain the drying weight, thereby ensuring the drying weight to be below 5%.
8. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S7, the dried filter cake is crushed by a micro-crusher or a super-micro-crusher, and then mixed by a mixer, and then the intermediate inspection is performed, specifically comprising the following steps:
(1) And (3) putting the dried filter cake into a feeding container of a micronizer, starting the micronizer, and carrying out crushing operation, wherein in the crushing process, attention is paid to observing the crushing condition, so that the dried filter cake is uniformly crushed, and no caking or overheating phenomenon exists.
(2) And (3) performing intermediate inspection on the mixed powder to ensure that the quality of the powder meets the expected requirements.
9. The process for producing silymarin with high dissolution rate according to claim 1, wherein in S8, the qualified finished product is packaged, and the specific steps are as follows:
(1) And placing qualified products into a packaging container to ensure accurate quantity without redundant or insufficient quantity.
(2) The packaging container is sealed well, so that the product is ensured not to leak or be polluted.
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