CN116236450A - Method for delaying browning in granulating process of glucosamine and sodium chondroitin sulfate - Google Patents
Method for delaying browning in granulating process of glucosamine and sodium chondroitin sulfate Download PDFInfo
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- CN116236450A CN116236450A CN202310351162.9A CN202310351162A CN116236450A CN 116236450 A CN116236450 A CN 116236450A CN 202310351162 A CN202310351162 A CN 202310351162A CN 116236450 A CN116236450 A CN 116236450A
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- glucosamine
- chondroitin sulfate
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- sodium chondroitin
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- 238000000034 method Methods 0.000 title claims abstract description 33
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 title claims abstract description 25
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 title claims abstract description 19
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 229960002442 glucosamine Drugs 0.000 title claims abstract description 19
- 239000000463 material Substances 0.000 claims abstract description 120
- 238000002156 mixing Methods 0.000 claims abstract description 28
- 238000005469 granulation Methods 0.000 claims abstract description 26
- 230000003179 granulation Effects 0.000 claims abstract description 26
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 11
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 11
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 11
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 11
- 239000008187 granular material Substances 0.000 claims abstract description 7
- 229920002567 Chondroitin Polymers 0.000 claims abstract description 5
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 claims abstract description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- 238000012216 screening Methods 0.000 claims description 22
- 238000009835 boiling Methods 0.000 claims description 15
- 239000013590 bulk material Substances 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- CBOJBBMQJBVCMW-BTVCFUMJSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;hydrochloride Chemical compound Cl.O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO CBOJBBMQJBVCMW-BTVCFUMJSA-N 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 11
- 229960001911 glucosamine hydrochloride Drugs 0.000 claims description 11
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 11
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 11
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 11
- 239000008213 purified water Substances 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 10
- PVXPPJIGRGXGCY-TZLCEDOOSA-N 6-O-alpha-D-glucopyranosyl-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)C(O)(CO)O1 PVXPPJIGRGXGCY-TZLCEDOOSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000007789 sealing Methods 0.000 claims description 8
- 241001233242 Lontra Species 0.000 claims description 6
- 230000007246 mechanism Effects 0.000 claims description 6
- 239000004320 sodium erythorbate Substances 0.000 claims description 5
- 239000004744 fabric Substances 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
- 235000011152 sodium sulphate Nutrition 0.000 claims description 3
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 claims description 2
- 239000000905 isomalt Substances 0.000 claims description 2
- 235000010439 isomalt Nutrition 0.000 claims description 2
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 claims description 2
- 238000007873 sieving Methods 0.000 claims description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium erythorbate Chemical compound [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 230000000979 retarding effect Effects 0.000 claims 1
- 239000000741 silica gel Substances 0.000 claims 1
- 229910002027 silica gel Inorganic materials 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 14
- 239000000843 powder Substances 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 5
- 229940006423 chondroitin sulfate sodium Drugs 0.000 abstract description 4
- -1 glucosamine series salt Chemical class 0.000 abstract description 4
- 230000003111 delayed effect Effects 0.000 abstract description 2
- 239000000080 wetting agent Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 description 21
- 239000002245 particle Substances 0.000 description 21
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 7
- 238000005550 wet granulation Methods 0.000 description 4
- 239000000654 additive Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000002274 desiccant Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000009434 installation Methods 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 206010027146 Melanoderma Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002301 glucosamine derivatives Chemical class 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Images
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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Abstract
The invention belongs to the field of granulation, and particularly relates to a method for delaying browning in the granulating process of glucosamine and sodium chondroitin sulfate, wherein the browning of health-care food is delayed by respectively and independently granulating glucosamine series salt and sodium chondroitin sulfate powder before mixing; when the glucosamine and the chondroitin are granulated together, the two materials are contacted fully, and because the wetting agent is added and finally the mixture is dried at high temperature, the Maillard reaction is promoted (the reaction is easy to be accelerated under high moisture and high temperature); the glucosamine series salt and the chondroitin sulfate sodium powder are respectively and independently granulated before being mixed to form granules, so that the glucosamine series salt and the chondroitin sulfate sodium powder are prevented from being simultaneously in a high-temperature environment; meanwhile, 0.5% -5% of hydroxypropyl methyl cellulose and polyvinyl alcohol are added during granulation, and a film is formed on the outer shape of the granules during granulation, so that the contact area between two substances is reduced, and the Maillard reaction between the two substances is slowed down.
Description
Technical Field
The invention relates to the field of granulation, in particular to a method for delaying browning in the granulation process of glucosamine and sodium chondroitin sulfate.
Background
The maillard reaction is also called a non-enzymatic browning reaction, which is a non-enzymatic browning widely existing in the food industry, and is a reaction between carbonyl compounds (reducing saccharides) and amino compounds (amino acids and proteins), and a complex process is carried out to finally generate brown or even black macromolecular melanoidins or melanoidins, so that the maillard reaction is also called a ketamine reaction.
The glucosamine series salt and the chondroitin sulfate sodium are classical formulas of the bone joint health-care food, but the two raw materials are mixed together, so that the amino group on the glucosamine is easy to react with carbonyl group on the chondroitin sulfate to generate Maillard reaction, and the Maillard reaction can be delayed to generate brown substances with time under the condition of temperature, moisture and PH change, thereby influencing the sense of the product.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention aims to provide a method for delaying browning in the granulating process of glucosamine and sodium chondroitin sulfate, which solves the technical problems.
In order to achieve the above purpose, the present invention provides the following technical solutions:
a method for delaying browning in a granulation process of glucosamine and sodium chondroitin sulfate, comprising the steps of:
s1, granulating: uniformly mixing chondroitin sodium sulfate and glucosamine hydrochloride, adding hydroxypropyl methylcellulose and polyvinyl alcohol dissolved in purified water, boiling and granulating, maintaining uniform granulating air inlet temperature to obtain dry material A,
uniformly mixing isomaltulose alcohol and microcrystalline cellulose, adding hydroxypropyl methylcellulose and polyvinyl alcohol dissolved in purified water, boiling and granulating, and maintaining uniform granulating air inlet temperature to obtain a dry material B;
s2, finishing: respectively sieving the two dry materials A, B in the step S1 with a screen to obtain granules, and collecting undersize materials;
s3, mixing: adding magnesium stearate into the two undersize products in the step S2, and uniformly mixing;
s4, tabletting: tabletting the mixture to obtain tablets.
Further, in step S1, sodium D-isoascorbate is added to sodium chondroitin sulfate and glucosamine hydrochloride, isomalt and microcrystalline cellulose.
Further, in the step S1, the pure water accounts for 25% of the total weight, the pure water contains 80 parts of sodium chondroitin sulfate, 80 parts of glucosamine hydrochloride, 30 parts of isomaltulose alcohol, 40 parts of microcrystalline cellulose, 1-5 parts of hydroxypropyl methylcellulose, 1-5 parts of polyvinyl alcohol and 10-20 parts of D-sodium erythorbate; the inlet air temperature of granulation is 65 ℃.
In step S2, a 14-mesh screen is selected for finishing, so that the yield is more than 85% of the total amount of the materials.
Further, in step S3, 1 to 4 parts of magnesium stearate is added.
Further, step S1 is performed in a fluidized drying granulator, and step S3 is performed in a stirrer and a mixer.
By adopting the technical scheme, the invention has the beneficial effects that:
1. when the glucosamine and the chondroitin are granulated together, the two materials are contacted fully, and because a wetting agent is added and finally the mixture is dried at high temperature, the Maillard reaction is promoted (the reaction is easy to be accelerated at high temperature and high moisture), and the glucosamine salt and the chondroitin sulfate sodium powder are granulated separately before being mixed to form granules, so that the two are prevented from being simultaneously in a high-temperature environment;
2. meanwhile, the hydroxypropyl methylcellulose and the polyvinyl alcohol added during granulation form a film on the appearance of the granules during granulation, so that the contact area between the two substances is reduced, and the Maillard reaction between the two substances is slowed down;
3. the D-sodium erythorbate added during granulation greatly increases the oxidation resistance of the medicine granules, and further greatly delays the browning reaction of the tablets.
Drawings
FIG. 1 is a schematic diagram of a fluidized bed dryer granulator.
Fig. 2 is a schematic view of a partial structure of the upper bin.
Fig. 3 is a schematic cross-sectional structural view of the bottom cartridge.
Fig. 4 is a schematic structural view of the stirrer.
Fig. 5 is a schematic cross-sectional view of a horizontal rotary drum.
Fig. 6 is a schematic structural view of the mixer.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled 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.
In the description of the present invention, it should be understood that the terms "upper," "lower," "front," "rear," "left," "right," "top," "bottom," "inner," "outer," and the like indicate or are based on the orientation or positional relationship shown in the drawings, merely to facilitate description of the present invention and to simplify the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be configured and operated in a specific orientation, and thus should not be construed as limiting the present invention.
Example 1 (Wet method, control)
(1) Granulating: uniformly mixing 80g of sodium chondroitin sulfate, 80g of glucosamine hydrochloride, 30g of isomaltulose alcohol and 40g of microcrystalline cellulose, and adding purified water accounting for 25% of the total weight for wet granulation; the soft material is sieved by a 14-mesh screen to obtain R1;
(2) And (3) drying: drying the undersize of the 14 mesh screen for 30min at the air inlet temperature of 60 ℃ to obtain a dried product G1.
(3) Finishing: the dried material is sieved by a 14-mesh screen for finishing grains, and the undersize material is collected, so that the yield is more than 85% of the total feeding amount of the material;
(4) Mixing: adding 2g of magnesium stearate into the sieved material after finishing, and uniformly mixing;
(5) Tabletting: the mixture was tabletted to obtain tablet P1.
Example 2 (Wet method, no effect)
(1) Granulating: uniformly mixing 80g of sodium chondroitin sulfate, 80g of glucosamine hydrochloride, 30g of isomaltulose alcohol, 40g of microcrystalline cellulose, 2g of hydroxypropyl methylcellulose and 2g of polyvinyl alcohol, and adding purified water accounting for 25% of the total weight for wet granulation; the soft material is sieved by a 14-mesh screen to obtain R2;
(2) And (3) drying: and (3) drying the undersize material of the 14-mesh screen mesh at the air inlet temperature of 60 ℃ for 30min to obtain a dried product G2.
(3) Finishing: the dried material is sieved by a 14-mesh screen for finishing grains, and the undersize material is collected, so that the yield is more than 85% of the total feeding amount of the material;
(4) Mixing: adding 2g of magnesium stearate into the sieved material after finishing, and uniformly mixing;
(5) Tabletting: tabletting the mixture to obtain tablet P2.
Example 3 (boiling, control)
(1) Granulating: uniformly mixing 80G of chondroitin sodium sulfate, 80G of glucosamine hydrochloride, 30G of isomaltulose alcohol and 40G of microcrystalline cellulose, adding purified water accounting for 25% of the total weight, and performing boiling granulation at an air inlet temperature of 65 ℃ to obtain a dried product G3.
(2) Finishing: the dried material is sieved by a 14-mesh screen for finishing grains, and the undersize material is collected, so that the yield is more than 85% of the total feeding amount of the material;
(3) Mixing: adding 2g of magnesium stearate into the sieved material after finishing, uniformly mixing,
tabletting: the mixture was tabletted to obtain tablet P3.
Example 4 (boiling, wall Material)
(1) Granulating: uniformly mixing 80g of sodium chondroitin sulfate and 80g of glucosamine hydrochloride, uniformly mixing 30g of isomaltulose alcohol and 40g of microcrystalline cellulose, dissolving 2g of hydroxypropyl methylcellulose and 2g of polyvinyl alcohol in purified water with the total weight of 25%, and respectively carrying out boiling granulation on the two materials, wherein the granulating air inlet temperature is 65 ℃, so as to respectively obtain a dry material A and a dry material B;
(2) Finishing: the dried material A and the dried material B are respectively sieved by a 14-mesh screen for finishing grains, and undersize materials A and B are collected, so that the yield is more than 85% of the total material feeding amount;
(3) Mixing: 2g of magnesium stearate is added into the undersize products A and B after finishing, and the mixture is uniformly mixed;
(4) Tabletting: the mixture was tabletted to obtain tablet P4.
Example 5 (boiling, additives, wall Material)
(1) Granulating: uniformly mixing 80g of sodium chondroitin sulfate, 80g of glucosamine hydrochloride and 8 g of D-sodium erythorbate to obtain a dried material A1, uniformly mixing 30g of isomaltulose alcohol, 40g of microcrystalline cellulose and 8 g of D-sodium erythorbate to obtain a dried material B1, dissolving 2g of hydroxypropyl methylcellulose and 2g of polyvinyl alcohol in purified water accounting for 25% of the total weight, and respectively carrying out boiling granulation on the two materials, wherein the granulating air inlet temperature is 65 ℃, so as to obtain the dried material A1 and the dried material B1 respectively;
(2) Finishing: the dried material A1 and the dried material B1 are sieved by a 14-mesh screen for finishing, and the undersize materials A1 and B1 are collected, so that the yield is more than 85% of the total feeding amount of the materials;
(3) Mixing: adding 2g of magnesium stearate into the sieved undersides A1 and B1 after finishing, and uniformly mixing;
(4) Tabletting: the mixture was tabletted to obtain tablet P5.
P1, P2, P3, P4, P5 were subjected to a high temperature test and a 37 ℃/75% accelerated stability test for 3 months, as follows:
high temperature test: the pressed tablets are placed in a bottle, added with a desiccant and sealed. Placing in oven at 60deg.C for 72 hr, and observing color change of the tablet before and after the tablet;
acceleration test: filling the pressed sheet into a bottle, adding a desiccant, and sealing; placing the bottles in a stability test box with the temperature of 37 ℃ and the humidity of 75%, taking out part of the bottles each month for observation and photographing, and carrying out three months altogether; the experimental conditions are shown in the following table:
finally, the conclusion is drawn:
embodiment one: wet granulation produces black spots + boiling dry- & gt black spots (ineffective);
embodiment two: wet granulation, wall material generation of black spots, boiling drying, and black spot (ineffective);
embodiment III: boiling granulation→browning (invalidation);
embodiment four: boiling granulation plus wall material → not significantly browning;
fifth embodiment: boiling granulation + additive + wall material → no browning.
Regarding the ebullated drying granulator:
as shown in fig. 1-3, the fluidized drying granulator comprises a frame 1, a top bin 2, a middle bin 3, a bottom bin 4, a collecting device 5 and a screening device 6, wherein the top bin 2 is fixed on the frame 1, the middle bin 3 is hinged with the frame 1 and rotates in the horizontal direction, the bottom bin 4 is detachably connected with the frame 1, the top bin 2, the middle bin 3 and the bottom bin 4 are sequentially sealed and butted from top to bottom, the collecting device 5 is arranged in the top bin 2, the screening device 6 is arranged in the bottom bin 4, the collecting device 5 comprises a mounting ring 51, a collecting cover 52, a disturbance ball 53 and a collecting screen 54, the collecting cover 52 and the collecting screen 54 are sequentially fixed on the mounting ring 51 from top to bottom, the cross section of the collecting cover 52 is arc-shaped and is composed of filter cloth, the collecting screen 54 is bowl-shaped, the collecting screen 54 and the collecting cover 52 form a olive-shaped collecting space, the disturbance ball 53 is arranged in the collecting space, and the disturbance ball 53 is composed of hollow elastic balls; screening device 6 includes installation bucket 61 and screening otter board 62, comprises the staving that is the pipe form and is annular spacing ring on the installation bucket 61, and the spacing ring is fixed in the top of staving, and screening otter board 62 is fixed in the staving, and screening otter board 62 comprises integrated into one piece's annular net piece and middle part net piece, and the cross-section of annular net piece is the U type, and middle part net piece is the bowl form of back-off, and open on the top of end storehouse 4 has the constant head tank 601 with the staving grafting, spacing ring and the bottom sealing connection of well storehouse 3, and it has the air intake to open on the end storehouse 4, and the air intake is arranged in screening device 6 below.
When the granulator is in operation, wind enters the bottom bin 4 from the air inlet and blows powdery materials into the middle bin 3, at the moment, the peristaltic pump pumps liquid auxiliary materials (formed by mixing additives, wall materials and purified water) into the middle bin 3 in a mist form and mixes the auxiliary materials with the materials to form particles, and the temperature is maintained to a proper degree, so that stable drying of formed medicine particles is ensured;
along with the granulating process, a part of materials enter the top bin 2 and are intercepted by the collecting device 5; when the material enters the collecting space through the rigid collecting screen plate 54, the material is intercepted by the filter plate, and the filter cloth is raised upwards and shakes under the action of wind force, so that the material powder is not easy to adhere to the filter cloth; under the action of wind force, the elastic disturbance ball 53 moves randomly in the collecting space, and the disturbance ball 53 impacts the collecting screen plate 54 and the collecting cover 52, so that the material powder adhered to the two is shaken off, and the material is not easy to remain in the top bin 2; the collecting device 5 is fixed in the top bin 2 through the mounting ring 51, and the collecting device 5 can be taken down by removing the mounting ring 51, so that the collecting device 5 is cleaned, materials remained on the collecting device 5 are prevented from being brown and then falling into processed materials again, and the quality of medicine particles is further influenced;
in the granulating process, powder at the bottom in the bottom bin 4 enters the middle bin 3 through the screening screen plate 62 under the action of wind force, and is mixed with auxiliary materials to be granulated and falls on the screening screen plate 62, the larger medicine particles are filtered and retained on the screening screen plate 62, and the smaller medicine particles fall back into the bottom bin 4 through the screening screen plate; over time, until no bottom bin 4 is present, the completion of granulation is achieved; the middle high side part of the screening screen plate 62 is low, so that the medicine particles falling on the screening screen plate slide to two sides, thereby freeing the middle and not affecting the granulation; the screening device 6 is connected with the bottom bin 4 through the plugging of the barrel body and the positioning groove, and then the barrel body and the positioning groove 601 can be disconnected, so that the screening device 6 is removed from the bottom bin 4 and cleaned; the middle bin 3 can horizontally rotate and is separated from the top bin 2 and the bottom bin 4, so that the top bin 2, the middle bin 3 and the top bin 2 can be cleaned conveniently.
Regarding the stirrer:
as shown in fig. 4 and 5, the stirrer comprises a base 71, a motor 72, a horizontal rotary cylinder 73, a sealing cover 74, a fan 75 and an air pipe 76, wherein the horizontal rotary cylinder 73 is arranged on the base 71 and is rotationally connected with a base, the motor 72 is fixed on the base 71 and drives the horizontal rotary cylinder 73 to rotate, the sealing cover 74 is hinged with the horizontal rotary cylinder 73, the fan 75 is connected with the air pipe 76, an air inlet 701 matched with the air pipe 76 is formed in the side end of the horizontal rotary cylinder 73, the air inlet is arranged in the middle of the side end of the horizontal rotary cylinder 73, a plurality of stirring sheets 77 are arranged on the inner wall of the horizontal rotary cylinder 73, the stirring sheets 77 are uniformly distributed around the axis of the horizontal rotary cylinder 73, each stirring sheet 77 is composed of integrally formed sheets and ends, the section of each sheet is isosceles trapezoid, and the section of each end is semicircular.
Two types of medicine particles and magnesium stearate are arranged in the horizontal rotary cylinder 73, and the horizontal rotary cylinder 73 is sealed by the sealing cover 74; the motor 72 drives the horizontal rotary cylinder 73 to rotate, and the stirring blade 77 stirs the materials in a disturbance manner, so that the uniform stirring of the materials is accelerated; the end parts of the stirring blades are large, the root parts are thick, then the space outlets formed by two adjacent stirring blades are relatively small, so that medicine particles in the space are more conveniently brought to the high position, uniform stirring of materials is realized, and the materials are not easy to damage due to the arrangement of the stirring blades; with the rotation of the horizontal rotary drum 73, the fan 75 is started and sends wind into the horizontal rotary drum 73 through the wind pipe 76, and magnesium stearate is more uniformly adhered to the two types of medicine particles under the action of wind force.
Regarding the mixer:
the mixer comprises a blanking device 81, a material guiding device 82, a material distributing device 83 and a bulk material device 84 which are sequentially connected from top to bottom, wherein the blanking device 81 comprises two blanking boxes 811, the material guiding device 82 is composed of a material receiving pipe 821 and a material guiding hopper 822, the material guiding hopper 822 is arranged in the material receiving pipe 821, the two blanking boxes 811 are respectively arranged at two sides of the material receiving pipe 821 and are communicated with the material receiving pipe 821, the material distributing device 83 comprises a material receiving box 831, a fixing rod 832 and a material distributing disc 833, the material receiving box 831 is communicated with the material receiving pipe 821, the side wall of the material receiving box 831 is arc-shaped, the section of the material distributing disc 833 is arc-shaped and is bent downwards, the fixing rod 832 and the material distributing disc 833 are arranged in the material receiving box 831 and are connected with the material receiving box 831, the material distributing disc 833 corresponds to the material guiding hopper 822, the bulk material distributing device 84 comprises a blanking pipe 841 and two groups of material distributing mechanisms, the material distributing mechanisms comprise an air cylinder 842, a connecting rod 843 and a bulk material distributing member 844, the bulk material distributing member 844 is arranged in the blanking pipe 841, the bulk material distributing member 841 and the blanking pipe 841 are movably connected with the blanking pipe 843, the bulk material distributing disc 843 is connected with the blanking plate 843 by the air cylinder 843, the material distributing plate 843 is connected with the blanking plate 801 in a reciprocating mode, and the bulk material connecting rod 801 is connected with the blanking plate 801 by the connecting rod 801, and the bulk material distributing device is connected with the bulk material connecting rod 801 by the bar 801.
Two kinds of medicine particles stirred with magnesium stearate are respectively filled into two blanking boxes 811, and then the medicine particles in the two blanking boxes 811 flow down into a receiving pipe 821 and are primarily mixed; then falls on the distributing disc 833 under the guide of the guide hopper 822, and the medicine particles fall on the top of the circular cap shape and then fall to the side of the distributing disc 833, so that the medicine particles are dispersed under the action of the distributing disc 833, thereby being convenient for the comprehensive contact and mixing of the two kinds of medicine particles; the medicine particles fall on the inner wall of the material receiving box 831 with a spherical space after passing through the material distributing disc 833, and the two kinds of medicine particles are mixed again in the material receiving box 831; then, the medicine particles enter the blanking pipe 841, and the cylinder 842 drives the bulk material plate 801 to swing up and down along with the medicine particles passing through the blanking pipe 841, so that the medicine particles falling on the bulk material plate 801 are lifted up and scattered, and further mixing of the two kinds of medicine particles is realized; under the action of the mixer, the two types of medicine particles are uniformly mixed together.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the invention, but one skilled in the art can make common changes and substitutions within the scope of the technical solution of the present invention.
Claims (10)
1. A method for delaying browning in a granulation process of glucosamine and sodium chondroitin sulfate, comprising the steps of:
s1, granulating: uniformly mixing chondroitin sodium sulfate and glucosamine hydrochloride, adding hydroxypropyl methylcellulose and polyvinyl alcohol dissolved in purified water, boiling and granulating, maintaining uniform granulating air inlet temperature to obtain dry material A,
uniformly mixing isomaltulose alcohol and microcrystalline cellulose, adding hydroxypropyl methylcellulose and polyvinyl alcohol dissolved in purified water, boiling and granulating, and maintaining uniform granulating air inlet temperature to obtain a dry material B;
s2, finishing: respectively sieving the dried material A and the dried material B in the step S1 by a screen to carry out granule finishing, and collecting undersize;
s3, mixing: adding magnesium stearate into the two undersize products in the step S2, and uniformly mixing;
s4, tabletting: tabletting the mixture to obtain tablets.
2. The method for delaying browning in a granulation process of glucosamine and sodium chondroitin sulfate according to claim 1, wherein in step S1, sodium D-isoascorbate is added to each of sodium chondroitin sulfate and glucosamine hydrochloride, isomalt and microcrystalline cellulose.
3. A method for delaying browning during granulation of glucosamine and sodium chondroitin sulfate according to claim 2, wherein,
in the step S1, the composition contains 80 parts of sodium chondroitin sulfate, 80 parts of glucosamine hydrochloride, 30 parts of isomaltulose alcohol, 40 parts of microcrystalline cellulose, 1-5 parts of hydroxypropyl methyl cellulose, 1-5 parts of polyvinyl alcohol and 10-20 parts of D-sodium erythorbate, wherein purified water accounts for 25% of the total weight; the inlet air temperature of granulation is 65 ℃.
4. A method for delaying browning during granulation of glucosamine and sodium chondroitin sulfate according to claim 2, wherein,
in the step S2, a 14-mesh screen is selected for finishing, so that the yield is more than 85% of the total amount of the materials;
in step S3, 1-4 parts of magnesium stearate is added.
5. A method of retarding browning during granulation of glucosamine and sodium chondroitin sulfate according to any of claims 1-4, wherein step S1 is performed in a fluid bed dryer granulator and step S3 is performed in a blender or mixer.
6. The method for delaying browning in a granulating process of glucosamine and sodium chondroitin sulfate according to claim 5, wherein the fluidized drying granulator comprises a frame, a top bin, a middle bin, a bottom bin, a collecting device and a screening device, wherein the top bin is fixed on the frame, the middle bin is hinged with the frame and rotates in the horizontal direction, the bottom bin is detachably connected with the frame, the top bin, the middle bin and the bottom bin are sequentially sealed and butted from top to bottom, the collecting device is arranged in the top bin, the screening device is arranged in the bottom bin,
the collecting device comprises a mounting ring, a collecting cover, a disturbance ball and a collecting screen plate, wherein the collecting cover and the collecting screen plate are sequentially fixed on the mounting ring from top to bottom, the cross section of the collecting cover is arc-shaped and is composed of filter cloth, the collecting screen plate is bowl-shaped, the collecting screen plate and the collecting cover form a collecting space which is football-shaped, the disturbance ball is arranged in the collecting space, and the disturbance ball is composed of hollow elastic balls.
7. A method for delaying browning during granulation of glucosamine and sodium chondroitin sulfate according to claim 6, wherein,
screening device includes mounting barrel and screening otter board, comprises being tubular staving and being annular spacing ring on the mounting barrel, and the spacing ring is fixed in the top of staving, and screening otter board is fixed in the staving, and the screening otter board comprises integrated into one piece's annular net piece and middle part net piece, and the cross-section of annular net piece is the U type, and the middle part net piece is the bowl form of back-off, and open on the top of end storehouse has the constant head tank of pegging graft with the staving, and spacing ring and the bottom sealing connection of well storehouse, open on the end storehouse has the air intake, and screening device below is arranged in to the air intake.
8. The method for delaying browning in a granulating process of glucosamine and sodium chondroitin sulfate according to claim 5, wherein the mixer comprises a blanking device, a material guiding device, a material distributing device and a material distributing device which are sequentially connected from top to bottom, the blanking device comprises two blanking boxes, the material guiding device comprises a material receiving pipe and a material guiding hopper, the material guiding hopper is arranged in the material receiving pipe, the two blanking boxes are respectively arranged on two sides of the material receiving pipe and are respectively communicated with the material receiving pipe, the material distributing device comprises a material receiving box, a fixing rod and a material distributing disc, the material receiving box is communicated with the material receiving pipe, the fixing rod and the material distributing disc are arranged in the material receiving box and are connected with the material distributing disc and the material receiving box, the material distributing disc corresponds to the material guiding hopper, the material distributing device comprises a blanking pipe and two material distributing mechanisms, the material distributing mechanism comprises a cylinder and a material distributing piece, the material distributing piece is arranged in the blanking pipe, the material distributing piece is movably connected with the blanking pipe, and the cylinder drives the material distributing piece to swing up and down.
9. The method for delaying browning in the granulation process of glucosamine and sodium chondroitin sulfate according to claim 8, wherein the distributing mechanism further comprises a connecting rod, the bulk material disturbance element is composed of a bulk material plate and a connecting rod which are connected with each other, a strip-shaped hole is formed in the blanking pipe, the connecting rod penetrates through the strip-shaped hole and is hinged with the connecting rod, and the cylinder is connected with the connecting rod; bulk cargo plates of the two groups of material distribution mechanisms are staggered;
the bulk cargo plate is composed of silica gel, the section of the distributing disc is arc-shaped and bent downwards, and the side wall of the receiving box is arc-shaped.
10. The method for delaying browning in a granulating process of glucosamine and sodium chondroitin sulfate according to claim 5, wherein the stirrer comprises a base, a motor, a horizontal rotating cylinder, a sealing cover, a fan and an air pipe, wherein the horizontal rotating cylinder is arranged on the base and is rotationally connected with the base, the motor is fixed on the base and drives the horizontal rotating cylinder to rotate, the sealing cover is hinged with the horizontal rotating cylinder, the fan is connected with the air pipe, an air inlet matched with the air pipe is formed in the side end of the horizontal rotating cylinder, and the air inlet is arranged in the middle of the side end of the horizontal rotating cylinder;
the inner wall of the horizontal rotary cylinder is provided with a plurality of stirring sheets, the stirring sheets are uniformly distributed around the axis of the horizontal rotary cylinder, each stirring sheet consists of a sheet part and an end part which are integrally formed, the section of each sheet body is in an isosceles trapezoid shape, and the section of each end part is in a semicircle shape.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310351162.9A CN116236450A (en) | 2023-03-29 | 2023-03-29 | Method for delaying browning in granulating process of glucosamine and sodium chondroitin sulfate |
| CN202410267325.XA CN118122209A (en) | 2023-03-29 | 2024-03-08 | Drug granule granulating system containing glucosamine and chondroitin sulfate sodium |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310351162.9A CN116236450A (en) | 2023-03-29 | 2023-03-29 | Method for delaying browning in granulating process of glucosamine and sodium chondroitin sulfate |
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| CN202410267325.XA Pending CN118122209A (en) | 2023-03-29 | 2024-03-08 | Drug granule granulating system containing glucosamine and chondroitin sulfate sodium |
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| CN202410267325.XA Pending CN118122209A (en) | 2023-03-29 | 2024-03-08 | Drug granule granulating system containing glucosamine and chondroitin sulfate sodium |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112715943A (en) * | 2020-12-29 | 2021-04-30 | 深圳太太药业有限公司 | Glucosamine chondroitin tablet containing active peptide and organic calcium and preparation method thereof |
| CN115590197A (en) * | 2022-11-07 | 2023-01-13 | 中化健康产业发展有限公司（Cn） | Glucosamine chondroitin granulation method and application thereof in preparation of glucosamine chondroitin product |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112715943A (en) * | 2020-12-29 | 2021-04-30 | 深圳太太药业有限公司 | Glucosamine chondroitin tablet containing active peptide and organic calcium and preparation method thereof |
| CN115590197A (en) * | 2022-11-07 | 2023-01-13 | 中化健康产业发展有限公司（Cn） | Glucosamine chondroitin granulation method and application thereof in preparation of glucosamine chondroitin product |
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