CN110227079A - One kind five ties up lysine particle and preparation method thereof - Google Patents
One kind five ties up lysine particle and preparation method thereof Download PDFInfo
- Publication number
- CN110227079A CN110227079A CN201910482389.0A CN201910482389A CN110227079A CN 110227079 A CN110227079 A CN 110227079A CN 201910482389 A CN201910482389 A CN 201910482389A CN 110227079 A CN110227079 A CN 110227079A
- Authority
- CN
- China
- Prior art keywords
- buffer
- particle
- vitamin
- lysine
- recipe quantity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002245 particle Substances 0.000 title claims abstract description 93
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 239000004472 Lysine Substances 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims description 31
- 239000000872 buffer Substances 0.000 claims abstract description 66
- 229960003646 lysine Drugs 0.000 claims abstract description 47
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 claims abstract description 41
- 229960002079 calcium pantothenate Drugs 0.000 claims abstract description 37
- 239000011726 vitamin B6 Substances 0.000 claims abstract description 27
- 239000011691 vitamin B1 Substances 0.000 claims abstract description 24
- 239000011716 vitamin B2 Substances 0.000 claims abstract description 23
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims abstract description 22
- 229960005337 lysine hydrochloride Drugs 0.000 claims abstract description 22
- 229930006000 Sucrose Natural products 0.000 claims abstract description 21
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 21
- 239000011230 binding agent Substances 0.000 claims abstract description 21
- 239000005720 sucrose Substances 0.000 claims abstract description 21
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims abstract description 17
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims abstract description 13
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 claims abstract description 11
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000011570 nicotinamide Substances 0.000 claims abstract description 10
- 229960003966 nicotinamide Drugs 0.000 claims abstract description 10
- 235000005152 nicotinamide Nutrition 0.000 claims abstract description 10
- 238000004806 packaging method and process Methods 0.000 claims abstract description 5
- 239000004375 Dextrin Substances 0.000 claims description 33
- 229920001353 Dextrin Polymers 0.000 claims description 33
- 235000019425 dextrin Nutrition 0.000 claims description 33
- 239000000843 powder Substances 0.000 claims description 24
- 229920002472 Starch Polymers 0.000 claims description 15
- 235000019698 starch Nutrition 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- -1 nicotinoyl Amine Chemical class 0.000 claims description 12
- 235000019441 ethanol Nutrition 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 9
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 239000002002 slurry Substances 0.000 claims description 7
- 238000005550 wet granulation Methods 0.000 claims description 7
- 229940088594 vitamin Drugs 0.000 claims description 6
- 229930003231 vitamin Natural products 0.000 claims description 6
- 235000013343 vitamin Nutrition 0.000 claims description 6
- 239000011782 vitamin Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 5
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 5
- 125000005909 ethyl alcohol group Chemical group 0.000 claims description 3
- FHUOTRMCFQTSOA-UHFFFAOYSA-M potassium;acetic acid;acetate Chemical compound [K+].CC(O)=O.CC([O-])=O FHUOTRMCFQTSOA-UHFFFAOYSA-M 0.000 claims description 3
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- ALSPKRWQCLSJLV-UHFFFAOYSA-N azanium;acetic acid;acetate Chemical compound [NH4+].CC(O)=O.CC([O-])=O ALSPKRWQCLSJLV-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- LVXHNCUCBXIIPE-UHFFFAOYSA-L disodium;hydrogen phosphate;hydrate Chemical compound O.[Na+].[Na+].OP([O-])([O-])=O LVXHNCUCBXIIPE-UHFFFAOYSA-L 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- QTYWBJZOZDYCGB-UHFFFAOYSA-L potassium;sodium;2-carboxybenzoate;hydroxide Chemical compound [OH-].[Na+].[K+].OC(=O)C1=CC=CC=C1C([O-])=O QTYWBJZOZDYCGB-UHFFFAOYSA-L 0.000 claims description 2
- LJSOLTRJEQZSHV-UHFFFAOYSA-L potassium;sodium;hydron;hydroxide;phosphate Chemical compound [OH-].[Na+].[K+].OP(O)([O-])=O LJSOLTRJEQZSHV-UHFFFAOYSA-L 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- IGHGOYDCVRUTSU-UHFFFAOYSA-M sodium;2-hydroxypropane-1,2,3-tricarboxylic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O IGHGOYDCVRUTSU-UHFFFAOYSA-M 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 claims description 2
- OLFJVIXNILIZKF-UHFFFAOYSA-N acetic acid;sodium Chemical compound [Na].CC(O)=O.CC(O)=O OLFJVIXNILIZKF-UHFFFAOYSA-N 0.000 claims 1
- SPOMEWBVWWDQBC-UHFFFAOYSA-K tripotassium;dihydrogen phosphate;hydrogen phosphate Chemical compound [K+].[K+].[K+].OP(O)([O-])=O.OP([O-])([O-])=O SPOMEWBVWWDQBC-UHFFFAOYSA-K 0.000 claims 1
- 239000011720 vitamin B Substances 0.000 abstract description 16
- 229930003270 Vitamin B Natural products 0.000 abstract description 15
- 235000019156 vitamin B Nutrition 0.000 abstract description 15
- 239000007853 buffer solution Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 17
- 238000007873 sieving Methods 0.000 description 16
- 239000011122 softwood Substances 0.000 description 11
- 239000003814 drug Substances 0.000 description 9
- 238000005469 granulation Methods 0.000 description 9
- 230000003179 granulation Effects 0.000 description 9
- 238000000643 oven drying Methods 0.000 description 9
- 239000007921 spray Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 238000013112 stability test Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 4
- 229960004543 anhydrous citric acid Drugs 0.000 description 4
- 235000019504 cigarettes Nutrition 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000008236 heating water Substances 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 240000000111 Saccharum officinarum Species 0.000 description 2
- 235000007201 Saccharum officinarum Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000008131 children development Effects 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to one kind five to tie up lysine particle, and A particle and B particle including separated packaging, the A particle includes lysine hydrochloride, calcium pantothenate, vitamin B2, vitamin B6, binder, sucrose and the first buffer；First buffer pH under solution state is 6.0-7.0；The B particle includes lysine hydrochloride, vitamin B1, vitamin B2, vitamin B6, niacinamide, binder, sucrose and the second buffer；Second buffer pH under solution state is 3.0-5.5；The A particle and lysine hydrochloride, vitamin B in B particle2And vitamin B6Mass ratio be 1:1.Calcium pantothenate and vitamin B in five dimension lysine particles of the invention1Stability is improved.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, more particularly to one kind five to tie up lysine particle and preparation method thereof.
Background technique
Five dimension lysine particles are vitamins non-prescribed medicine compound preparation, and every gram containing 50 milligrams of lysine hydrochlorides, 1.2 millis
Gram vitamin B1, 0.15 milligram of vitamin B2, 0.075 milligram of vitamin B6, 2.4 milligrams of niacinamide, 0.15 milligram of calcium pantothenate,
Yu Zewei auxiliary material sucrose, for promoting children, proper child development and the nutritional supplementation of elderly and infirm.
Five dimension lysine particles can be directed to the growth and development characteristics reasonable supplement needed by human body of children.Lysine can promote
Damaged nerve tissue is repaired in growth and development；Vitamin B1And B6The formation of internal coenzyme is participated in, metabolism in vivo is promoted；Pantothenic acid
Calcium participates in the formation of skeleton, the reconstruction of bone tissue, contraction of muscle, neurotransmission, clotting mechanism and maintains capillary
Permeability etc..Five dimension lysine particles can supplement the lysine of infant loss, and constitution not only can be enhanced, improve disease resistance,
And the secretion of infant pepsin can be promoted, to form a kind of benign cycle effect over the course for the treatment of.
Main component in five dimension lysine particles is water soluble vitamin, and stability is relatively low, especially vitamin B1With
Influence of the calcium pantothenate vulnerable to environmental factor such as light, high temperature and water causes transport and preservation condition to require high, using also by very
Big limitation.
The national drug standards have recorded five dimension lysine particles, but because its principal component content is low, stability problem is extremely
Such as there is slightly changes of contents, then significantly affect its quality in key.The Chinese patent of Publication No. CN107233305A discloses
One kind five ties up lysine oral solution, and CN201510217486.9 discloses a kind of dimension of lysine five comprising chiral photo-isomerisation compound
Medical composition and its use.And currently, there is not yet for vitamin B in five dimension lysine particles1With pantothenic acid calcium stability
Relevant research report.
Summary of the invention
In order to solve the above technical problems, the object of the present invention is to provide one kind five to tie up lysine particle and preparation method thereof,
The stability for improving ingredients Vitamin B1 and calcium pantothenate degradable in prescription, extends the pot-life in different environments, from
And guarantee the quality and validity of said preparation.
The first purpose of the invention is to provide one kind five to tie up lysine particle, including the A particle of separated packaging and B
Grain, the A particle includes lysine hydrochloride, calcium pantothenate, vitamin B2, vitamin B6, niacinamide, binder, sucrose and first slow
Electuary；First buffer pH under solution state is 6.0-7.0；
The B particle includes lysine hydrochloride, vitamin B1, vitamin B2, vitamin B6, binder, sucrose and second slow
Electuary；Second buffer pH under solution state is 3.0-5.5；
The A particle and lysine hydrochloride, vitamin B in B particle2And vitamin B6Mass ratio be 1:1.
Preferably, the first buffer pH under solution state is 6.0-6.8, more preferably 6.3-6.5.
Preferably, the second buffer pH under solution state is 3.5-4.0.
It further, include 50 milligrams of lysine hydrochlorides, 1.2 milligrams of vitamin Bs in every gram five dimension lysine particle1、
0.15 milligram of vitamin B2, 0.075 milligram of vitamin B6, 2.4 milligrams of niacinamide, 0.15 milligram of calcium pantothenate, 920-950 milligrams of sugarcanes
Sugar.
Further, binder is selected from one of starch slurry, dextrin, gelatin, sodium carboxymethylcellulose, PVP and ethyl alcohol
Or it is a variety of.
Further, binder is preferably ethyl alcohol, PVP or dextrin.
Further, the volume of buffer solution used in every 50 grams of A particles or B particle is 1.5-2.5mL, buffer solution
In include the first buffer or the second buffer, the concentration of buffer solution is 0.01mol.L-1~0.2mol.L-1, and buffer molten
Contain 60% (w/v)~90% (w/v) ethyl alcohol or 1% (w/v)~10% (w/v) PVP or 1% (w/v)~10% (w/ in liquid
V) dextrin.
Further, the first buffer and the second buffer are selected from first buffer and the second buffer independently selects
From citric acid-sodium hydroxide, citric acid-sodium citrate, Potassium Hydrogen Phthalate-sodium hydroxide, Acetic acid-sodium acetate, acetic acid-vinegar
Sour potassium, acetic acid-potassium acetate, acetic acid-ammonium acetate, phosphoric acid-phosphoric citrate, sodium dihydrogen phosphate-disodium hydrogen phosphate, biphosphate
One or both of potassium-dipotassium hydrogen phosphate, sodium dihydrogen phosphate-sodium hydroxide, potassium dihydrogen phosphate-sodium hydroxide.
Preferably, the first buffer and the second buffer are citric acid-sodium citrate.
It further, further include corrigent in five dimension lysine particles.
A second object of the present invention is to provide a kind of preparation methods of above-mentioned five dimensions lysine particle, including following step
It is rapid:
(1) binder is dissolved in water with the first buffer and the second buffer respectively, obtains the first buffer and second and delays
Fliud flushing, the pH of first buffer are 6.0-7.0, and the pH of the second buffer is 3.0-5.5；
(2) 1/2 recipe quantity sucrose and 1/2 recipe quantity lysine hydrochloride are uniformly mixed respectively, obtain powder；
By calcium pantothenate and 1/2 recipe quantity vitamin B2, 1/2 recipe quantity vitamin B6It is dissolved in the first buffer, by what is obtained
Solution and powder mix, and wet granulation simultaneously obtains A particle after drying；
By vitamin B1, niacinamide, 1/2 recipe quantity vitamin B2With 1/2 recipe quantity vitamin B6It is dissolved in the second buffer
In, obtained solution and powder are mixed, wet granulation simultaneously obtains B particle after drying；
A particle and B particle are packed respectively, obtain the five dimensions lysine particle.
Further, binder is preferably ethyl alcohol, PVP or dextrin.Contain in first buffer or in the second buffer
60% (w/v)~90% (w/v) ethyl alcohol or 1% (w/v)~10% (w/v) PVP or 1% (w/v)~10% (w/v) dextrin.
Preferably, the pH of the first buffer is 6.0-6.8, more preferably 6.3-6.5.
Preferably, the pH of the second buffer is 3.0-5.5, more preferably 3.5-4.0.
Further, in step (1), the concentration of first buffer or the second buffer is 0.01mol.L-1~
0.2mol.L-1。
Further, in step (2), the sucrose and lysine hydrochloride before mixing, cross 80-100 mesh.
Further, in step (2), when wet granulation, obtained particle is crossed into 18~28 meshes.
Further, in step (2), when every preparation 50g A particle, by calcium pantothenate and 1/2 recipe quantity vitamin B2、1/
2 recipe quantity vitamin Bs6It is dissolved in the first buffer of 2mL, by obtained spray solution in powder surface, is uniformly mixed, then spray
The first buffer of 1.5mL, softwood processed, sieving squeeze granulation, obtain A particle after dry.
Further, in step (2), when every preparation 50g B particle, by vitamin B1, niacinamide, 1/2 recipe quantity dimension
Raw element B2With 1/2 recipe quantity vitamin B6It is dissolved in the second buffer of 1-2mL, by obtained spray solution in powder surface, mixing
Uniformly, then the second buffer of 1-1.5mL, softwood processed are sprayed, sieving squeezes granulation, obtains A particle after dry.
Further, in step (2), drying temperature is 40 DEG C.
According to the physicochemical property and color of drug, A, B particle are prepared respectively, and the pH value of binder is adjusted by buffer,
Meet vitamin B1With the microenvironment of calcium pantothenate；By separated packaging, drug caused by further preventing moisture absorption or solvent to volatilize
The variation of pH guarantees the constant of pharmaceutical environment pH value, to realize vitamin B1With the stability of calcium pantothenate.
According to the above aspect of the present invention, the present invention has at least the following advantages:
(1) using five dimensions lysine particle produced by the present invention, drug granule environment is controlled respectively by buffer solution system
PH value, fully ensured that vitamin B1With the stability of calcium pantothenate.
(2) using five dimensions lysine particle produced by the present invention, use binder auxiliary material as a small amount of as possible does not influence medicine
The measurement of object content, mouthfeel do not change, and are suitble to old man and children to use, are remarkably improved patient medication compliance
(3) preparation method of five dimensions lysine particle disclosed by the invention, using wet granulation process, simple process, preparation
Condition is controllable, is conducive to industrialized production.
The above description is only an overview of the technical scheme of the present invention, in order to better understand the technical means of the present invention,
And can be implemented in accordance with the contents of the specification, with presently preferred embodiments of the present invention and cooperation, detailed description is as follows below.
Specific embodiment
With reference to embodiment, the embodiment of the present invention is furthur described in detail.Following embodiment is used for
Illustrate the present invention, but is not intended to limit the scope of the invention.
In implementing below the present invention, vitamin B in five dimension lysine particles1Such as with the stability testing method of calcium pantothenate
Under:
Made five dimensions lysine particle is respectively placed in room temperature (25 DEG C), climatic chamber (40 DEG C, 75%RH) and is done
Dry case (60 DEG C), is kept in dark place, and samples in the 0th, 5,10,20,30 day.Precision weighs 1g sample, and distilled water is added to be dissolved in 20mL
In volumetric flask, with 0.45 μm of membrane filtration, supernatant is taken, carries out HPLC analysis, calculates vitamin B1With the content (n of calcium pantothenate
=3).
Calcium pantothenate and vitamin B in five dimension lysine particles1HPLC analysis condition it is as follows:
(1) assay of calcium pantothenate: chromatographic column, C18Reverse-phase chromatographic column (250mm × 4.6mm, 5 μm)；Mobile phase, first
Alcohol: water (containing 0.1% phosphoric acid)=20:80 (V/V)；Detection wavelength, 210nm；Column temperature, 30 DEG C；Flow velocity, 1mL.min-1；Sample volume,
20μL。
(2) vitamin B1Assay: chromatographic column, C18Reverse-phase chromatographic column (150mm × 4.6mm, 5 μm)；Mobile phase,
0.008mol.L-1Sodium hexanesulfonate-methanol-glacial acetic acid-triethylamine (775:220:7.5:0.2)；Detection wavelength, 280nm；Column
Temperature, 30 DEG C；Flow velocity, 1mL.min-1；Sample volume, 20 μ L.
The preparation of embodiment First Five-Year Plan dimension lysine particle
It include 50 milligrams of lysine hydrochlorides, 1.2 milligrams of vitamin Bs in every gram five dimension lysine particle in the present invention1、
0.15 milligram of vitamin B2, 0.075 milligram of vitamin B6, 2.4 milligrams of niacinamide, 0.15 milligram of calcium pantothenate, 920-950 milligrams of sugarcanes
Sugar.Preparation method is as follows:
(1) prepared by binder: weighing anhydrous citric acid and sodium citrate, is each configured to pH6.6 and pH 4.0
(0.1mol.L-1) buffer.100mL buffer is measured respectively, 7g dextrin is added, and 100 DEG C of heating water bath 5min dissolutions are matched respectively
It is set to 7% dextrin that pH is 6.6 and pH 4.0 and starches buffer solution.
(2) 1/2 recipe quantity sucrose and the (sieving 80 of 1/2 recipe quantity lysine hydrochloride A particle preparation: are weighed#), move to beaker
(1L) obtains powder after mixing.By calcium pantothenate, 1/2 recipe quantity vitamin B2With 1/2 recipe quantity vitamin B6Being dissolved in 2mLpH is
In 6.6 7% dextrin slurry buffer solution, obtained solution 1.0mL is sprayed on precision and is weighed in about 50g powder, is mixed, then to
7% dextrin that 1.0mLpH is 6.6 is sprayed in mixture and starches buffer solution, is mixed, softwood processed, is crossed 24 mesh screens and is squeezed granulation, in
40 DEG C of oven drying 30min to get.
(3) B particle preparation: (the sieving 80 of 1/2 recipe quantity sucrose is weighed#) and (sieving 80 of 1/2 recipe quantity lysine hydrochloride#),
Beaker (1L) is moved to, obtains powder after mixing.By vitamin B1, 1/2 recipe quantity vitamin B2, 1/2 recipe quantity vitamin B6And cigarette
Amide is dissolved in 7% dextrin that 1.0mLpH is 4.0 and starches in buffer solution, and obtained spray solution is weighed about 50g powder in precision
In, it mixes, then 7% dextrin that sprinkling is added that about 1.0mLpH is 4.0 into mixture starches buffer solution, mixes, softwood processed, mistake
24 mesh screens squeeze granulation, in 40 DEG C of oven drying 30min to get.
Using valve bag, A particle and B particle are separately packed, every bag of 1g, to vitamin B therein1Distinguish with calcium pantothenate
Carry out study on the stability.The results are shown in Table 1.
1 vitamin B of table1With the stability test result (%, average value ± SD, n=3) of calcium pantothenate
Stability test is the results show that under the scheme of the present invention, calcium pantothenate and vitamin B1All have higher stabilization
Property, it is still initial 90% or more in the content of 30d.
The preparation of the dimension lysine particle of embodiment two or five
The present embodiment has investigated influence of the buffer concentration to pantothenic acid calcium stability in five dimension lysine particles.
(1) prepared by binder: weighing anhydrous citric acid and sodium citrate, is each configured to pH6.6 and pH5.2 (each pH
Under the conditions of the concentration of buffer solution be respectively 0.1mol.L-1And 0.01mol.L-1) buffer.100mL buffer is measured, is added
Enter 7g dextrin, 100 DEG C of heating water bath 5min dissolutions are each configured to the 7% dextrin slurry buffer solution of pH6.6 and pH5.2.
(2) 1/2 recipe quantity sucrose and the (sieving 80 of 1/2 recipe quantity lysine hydrochloride A particle preparation: are weighed#), move to beaker
(1L).By calcium pantothenate, 1/2 recipe quantity vitamin B2With 1/2 recipe quantity vitamin B6It is slow to be dissolved in the 7% dextrin slurry that 1mLpH is 6.6
It rushes in solution, obtained spray solution is weighed in about 50g powder in precision, mix, then spray and be added into mixture
7% dextrin that 1.0mLpH is 6.6 starches buffer solution, mixes, softwood processed, crosses 24 mesh screens and squeezes granulation, in 40 DEG C of oven dryings
30min to get.
(3) B particle preparation: (the sieving 80 of 1/2 recipe quantity sucrose is weighed#) and (sieving 80 of 1/2 recipe quantity lysine hydrochloride#),
Beaker (1L) is moved to, obtains powder after mixing.By vitamin B1, 1/2 recipe quantity vitamin B2, 1/2 recipe quantity vitamin B6And cigarette
Amide is dissolved in 7% dextrin that 1.0mLpH is 5.2 and starches in buffer solution, and obtained spray solution is weighed about 50g powder in precision
On, it mixes, then 7% dextrin that sprinkling is added that about 1.0mLpH is 5.2 into mixture starches buffer solution, mixes, softwood processed, mistake
24 mesh screens squeeze granulation, in 40 DEG C of oven drying 30min to get.
Using valve bag, (particle A: particle B=1:1) is taken to be packed with every bag of 2g, to vitamin B therein1With
Calcium pantothenate carries out study on the stability respectively.As a result as shown in table 2-3.
2. buffer concentration of table is to calcium pantothenate stability influence (%, Mean ± SD, n=3) in five dimension lysine particles
3. buffer concentration of table is to vitamin B in five dimension lysine particles1Stability influence (%, Mean ± SD, n=3)
By table 2-3 as it can be seen that being prepared into A particle and B particle, and when adjusting separately optimum pH, vitamin B1With calcium pantothenate
For content 90% or more, this formulation and technology conspicuousness improves the stability of two kinds of drugs.
The preparation of comparative example First Five-Year Plan dimension lysine particle
(1) prepared by binder: weighing anhydrous citric acid and sodium citrate, is each configured to pH5.8 and pH5.5
(0.1mol.L-1) buffer measures 100mL buffer respectively, 7g dextrin is added, 100 DEG C of heating water bath 5min dissolutions are matched respectively
It is set to 7% dextrin that pH is 5.8 and pH5.5 and starches buffer solution.
(2) 1/2 recipe quantity sucrose and the (sieving 80 of 1/2 recipe quantity lysine hydrochloride A particle preparation: are weighed#), move to beaker
(1L) obtains powder after mixing.By calcium pantothenate, 1/2 recipe quantity vitamin B2With 1/2 recipe quantity vitamin B6It is dissolved in 1mL pH
In 5.5 7% dextrin slurry buffer solution, obtained spray solution is weighed in about 50g powder in precision, is mixed, then to mixing
7% dextrin that sprinkling is added that 1.0mLpH is 5.5 in object starches buffer solution, mixes, softwood processed, crosses 24 mesh screens and squeezes granulation, in
40 DEG C of oven drying 30min to get.
(3) B particle preparation: (the sieving 80 of 1/2 recipe quantity sucrose is weighed#) and (sieving 80 of 1/2 recipe quantity lysine hydrochloride#),
It moves to after beaker (1L) is mixed and obtains powder.By vitamin B1, 1/2 recipe quantity vitamin B2, 1/2 recipe quantity vitamin B6And cigarette
Amide is dissolved in 7% dextrin that 1.0mLpH is 5.8 and starches in buffer solution, is sprayed on precision and weighs in about 50g powder, mixes, then to
7% dextrin that sprinkling is added that about 1.0mLpH is 5.8 in mixture starches buffer solution, mixes, softwood processed, crosses 24 mesh screens and squeezes
Granulation, in 40 DEG C of oven drying 30min to get.
Using valve bag, particle A and particle B are separately packed, every bag of 1g, to vitamin B therein1With calcium pantothenate respectively into
Row study on the stability.The results are shown in Table 4.
4 vitamin B of table1With the stability test result (%, average value ± SD, n=3) of calcium pantothenate
Stability test is the results show that under conditions of binder solution pH is 5.8 and 5.5, calcium pantothenate and vitamin B1
Very fast downward trend is presented.
The preparation of the dimension lysine particle of comparative example two or five
(1) prepared by binder: weighing anhydrous citric acid and sodium citrate, is configured to pH4.0 (0.1mol.L-1) buffer.
100mL buffer is measured, 7g dextrin is added, 100 DEG C of heating water bath 5min dissolutions are configured to the 7% dextrin slurry buffering that pH is 4.0
Solution.In addition the aqueous solution of 7% dextrin is configured.
(2) 1/2 recipe quantity sucrose and the (sieving 80 of 1/2 recipe quantity lysine hydrochloride A particle preparation: are weighed#), move to beaker
(1L) obtains powder after mixing.By calcium pantothenate, 1/2 recipe quantity vitamin B2With 1/2 recipe quantity vitamin B6It is dissolved in 1mL7% paste
In the aqueous solution of essence, obtained spray solution is weighed in about 50g powder in precision, mixed, then sprayed and be added into mixture
The aqueous solution of 1.0mL7% dextrin, mix, softwood processed, cross 24 mesh screens squeeze granulation, in 40 DEG C of oven drying 30min to get.
(3) B particle preparation: (the sieving 80 of 1/2 recipe quantity sucrose is weighed#) and (sieving 80 of 1/2 recipe quantity lysine hydrochloride#),
It moves to after beaker (1L) is mixed and obtains powder.By vitamin B1, 1/2 recipe quantity vitamin B2, 1/2 recipe quantity vitamin B6And cigarette
Amide is dissolved in 7% dextrin that 1.0mLpH is 4.0 and starches in buffer solution, is sprayed on precision and weighs in about 50 grams of powder, mixes, then
7% dextrin that sprinkling is added that about 1.0mLpH is 4.0 into mixture starches buffer solution, mixes, softwood processed, crosses 24 mesh screens and squeezes
Suppress grain, in 40 DEG C of oven drying 30min to get.
Using valve bag, particle A and particle B are separately packed, every bag of 1g, to vitamin B therein1With calcium pantothenate respectively into
Row study on the stability.The results are shown in Table 5.
5 vitamin B of table1With the stability test result (%, average value ± SD, n=3) of calcium pantothenate
Investigate the result shows that, using without buffer adjust pH be used as in the A particle of binder, pantothenic acid calcium content decreased show
It writes；In the B particle that buffer adjusts pH value, vitamin B1It is relatively stable.
The preparation of the dimension lysine particle of comparative example three or five
Weigh (the sieving 80 of recipe quantity sucrose#) and lysine hydrochloride (sieving 80#), it moves to beaker (1L), mixes.Dimension is given birth to
Plain B1, vitamin B2, vitamin B6, calcium pantothenate and niacinamide be dissolved in 7% dextrin in aqueous solution of 1.0mL, be sprayed on above-mentioned powder
In, it mixes, then 7% dextrin in aqueous solution of 1.0mL is added in sprinkling into mixture, mixes, softwood processed, cross 24 mesh screens and squeeze system
Grain, in 40 DEG C of oven drying 30min to get valve bag packaging carries out study on the stability.The results are shown in Table 6.
6 vitamin B of table1With the stability test result (%, average value ± SD, n=3) of calcium pantothenate
As shown in Table 6, five dimension lysine particles of conventional method preparation, pantothenic acid under the conditions of accelerated test, in drug
Calcium and vitamin B1Content is in significant downward trend.
The above is only a preferred embodiment of the present invention, it is not intended to restrict the invention, it is noted that for this skill
For the those of ordinary skill in art field, without departing from the technical principles of the invention, can also make it is several improvement and
Modification, these improvements and modifications also should be regarded as protection scope of the present invention.
Claims (10)
1. one kind five ties up lysine particle, it is characterised in that: A particle and B particle including separated packaging, the A particle include
Lysine hydrochloride, calcium pantothenate, vitamin B2, vitamin B6, binder, sucrose and the first buffer；First buffer is molten
PH is 6.0-7.0 under liquid status；
The B particle includes lysine hydrochloride, vitamin B1, vitamin B2, vitamin B6, niacinamide, binder, sucrose and
Two buffers；Second buffer pH under solution state is 3.0-5.5.
2. five dimensions lysine particle according to claim 1, it is characterised in that: include 50 in every gram five dimension lysine particle
Milligram lysine hydrochloride, 1.2 milligrams of vitamin Bs1, 0.15 milligram of vitamin B2, 0.075 milligram of vitamin B6, 2.4 milligrams of nicotinoyl
Amine, 0.15 milligram of calcium pantothenate and 920-950 milligrams of sucrose.
3. it is according to claim 1 five dimension lysine particle, it is characterised in that: the binder be selected from starch slurry, dextrin,
One of gelatin, sodium carboxymethylcellulose, PVP and ethyl alcohol are a variety of.
4. five dimensions lysine particle according to claim 1, it is characterised in that: first buffer and the second buffer
Independently selected from citric acid-sodium hydroxide, citric acid-sodium citrate, Potassium Hydrogen Phthalate-sodium hydroxide, acetic acid-acetic acid
Sodium, acetic acid-potassium acetate, acetic acid-potassium acetate, acetic acid-ammonium acetate, phosphoric acid-phosphoric citrate, sodium dihydrogen phosphate-disodium hydrogen phosphate,
One or both of potassium dihydrogen phosphate-dipotassium hydrogen phosphate, sodium dihydrogen phosphate-sodium hydroxide and potassium dihydrogen phosphate-sodium hydroxide.
5. five dimensions lysine particle according to claim 1, it is characterised in that: further include corrigent.
6. a kind of preparation method of five dimensions lysine particle of any of claims 1-5, which is characterized in that including with
Lower step:
(1) binder is dissolved in water with the first buffer and the second buffer respectively, obtains the first buffer and the second buffer,
The pH of first buffer is 6.0-7.0, and the pH of the second buffer is 3.0-5.5；
(2) 1/2 recipe quantity sucrose and 1/2 recipe quantity lysine hydrochloride are uniformly mixed respectively, obtain powder；
By calcium pantothenate and 1/2 recipe quantity vitamin B2, 1/2 recipe quantity vitamin B6It is dissolved in the first buffer, the solution that will be obtained
It is mixed with the powder, wet granulation simultaneously obtains A particle after drying；
By vitamin B1, niacinamide, 1/2 recipe quantity vitamin B2With 1/2 recipe quantity vitamin B6It is dissolved in the second buffer, it will
Obtained solution and the powder mix, and wet granulation simultaneously obtains B particle after drying；
A particle and B particle are packed respectively, obtain the five dimensions lysine particle.
7. preparation method according to claim 6, it is characterised in that: in step (1), binder is ethyl alcohol, PVP or paste
Essence contains 60% (w/v)~90% (w/v) ethyl alcohol, 1% (w/v)~10% (w/v) in the first buffer or in the second buffer
PVP or 1% (w/v)~10% (w/v) dextrin.
8. preparation method according to claim 6, it is characterised in that: in step (1), first buffer or second
The concentration of buffer is 0.01mol.L-1~0.2mol.L-1。
9. preparation method according to claim 6, it is characterised in that: in step (2), the sucrose and lysine hydrochloride
Before mixing, 80-100 mesh is crossed.
10. preparation method according to claim 6, it is characterised in that: in step (2), when wet granulation, by what is obtained
Particle crosses 18 mesh~28 meshes.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114259059A (en) * | 2021-12-09 | 2022-04-01 | 海南金贝康制药有限公司 | Multivitamin calcium-zinc chewable tablet and preparation method thereof |
| CN117643576A (en) * | 2024-01-30 | 2024-03-05 | 江西滕王阁药业有限公司 | Preparation method of granules containing lysine hydrochloride and glucose |
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| CN114259059A (en) * | 2021-12-09 | 2022-04-01 | 海南金贝康制药有限公司 | Multivitamin calcium-zinc chewable tablet and preparation method thereof |
| CN114259059B (en) * | 2021-12-09 | 2023-10-20 | 海南金贝康制药有限公司 | Multivitamin calcium zinc chewable tablet and preparation method thereof |
| CN117643576A (en) * | 2024-01-30 | 2024-03-05 | 江西滕王阁药业有限公司 | Preparation method of granules containing lysine hydrochloride and glucose |
| CN117643576B (en) * | 2024-01-30 | 2024-04-16 | 江西滕王阁药业有限公司 | Preparation method of granules containing lysine hydrochloride and glucose |
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