CN101961321A - Zinc gluconate sugar tablet preparation and preparation method thereof - Google Patents
Zinc gluconate sugar tablet preparation and preparation method thereof Download PDFInfo
- Publication number
- CN101961321A CN101961321A CN 201010285206 CN201010285206A CN101961321A CN 101961321 A CN101961321 A CN 101961321A CN 201010285206 CN201010285206 CN 201010285206 CN 201010285206 A CN201010285206 A CN 201010285206A CN 101961321 A CN101961321 A CN 101961321A
- Authority
- CN
- China
- Prior art keywords
- sugar
- zinc gluconate
- tablet
- preparation
- vacuum
- 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
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 title claims abstract description 119
- 229960000306 zinc gluconate Drugs 0.000 title claims abstract description 118
- 239000011670 zinc gluconate Substances 0.000 title claims abstract description 118
- 235000011478 zinc gluconate Nutrition 0.000 title claims abstract description 118
- 238000002360 preparation method Methods 0.000 title claims abstract description 52
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 56
- 239000006188 syrup Substances 0.000 claims abstract description 36
- 235000020357 syrup Nutrition 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 36
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 28
- 239000004471 Glycine Substances 0.000 claims abstract description 28
- 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 24
- 229930006000 Sucrose Natural products 0.000 claims abstract description 24
- 239000008213 purified water Substances 0.000 claims abstract description 21
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims abstract description 20
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims abstract description 20
- 238000009835 boiling Methods 0.000 claims abstract description 18
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 17
- 239000008103 glucose Substances 0.000 claims abstract description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 25
- 239000008369 fruit flavor Substances 0.000 claims description 23
- 238000001816 cooling Methods 0.000 claims description 15
- 239000006200 vaporizer Substances 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 13
- 235000011194 food seasoning agent Nutrition 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 238000005303 weighing Methods 0.000 claims description 11
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 238000007493 shaping process Methods 0.000 claims description 4
- 238000009413 insulation Methods 0.000 claims description 3
- 239000003826 tablet Substances 0.000 abstract description 96
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 abstract description 14
- 229940046011 buccal tablet Drugs 0.000 abstract description 8
- 239000006189 buccal tablet Substances 0.000 abstract description 8
- 201000009240 nasopharyngitis Diseases 0.000 abstract description 8
- 210000001331 nose Anatomy 0.000 abstract description 6
- 210000003695 paranasal sinus Anatomy 0.000 abstract description 5
- 241000712461 unidentified influenza virus Species 0.000 abstract description 4
- 102000018265 Virus Receptors Human genes 0.000 abstract description 3
- 108010066342 Virus Receptors Proteins 0.000 abstract description 3
- 239000000796 flavoring agent Substances 0.000 abstract description 2
- 235000013399 edible fruits Nutrition 0.000 abstract 1
- 235000013355 food flavoring agent Nutrition 0.000 abstract 1
- 239000012466 permeate Substances 0.000 abstract 1
- 210000004877 mucosa Anatomy 0.000 description 26
- 238000012360 testing method Methods 0.000 description 20
- 206010022000 influenza Diseases 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- 210000000214 mouth Anatomy 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- 239000003814 drug Substances 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000003203 everyday effect Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 210000002200 mouth mucosa Anatomy 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 229960000329 ribavirin Drugs 0.000 description 5
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 5
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 4
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 description 4
- 241000287828 Gallus gallus Species 0.000 description 4
- 229940087511 calcium disodium versenate Drugs 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 229960003291 chlorphenamine Drugs 0.000 description 4
- 231100000682 maximum tolerated dose Toxicity 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000004570 mortar (masonry) Substances 0.000 description 4
- 210000003800 pharynx Anatomy 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 238000010998 test method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 239000007922 nasal spray Substances 0.000 description 3
- 229940097496 nasal spray Drugs 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 230000014860 sensory perception of taste Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 206010039101 Rhinorrhoea Diseases 0.000 description 2
- 244000061458 Solanum melongena Species 0.000 description 2
- 206010041349 Somnolence Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 229940121657 clinical drug Drugs 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 229940124579 cold medicine Drugs 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000003628 erosive effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- ORFSSYGWXNGVFB-UHFFFAOYSA-N sodium 4-amino-6-[[4-[4-[(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonic acid Chemical compound COC1=C(C=CC(=C1)C2=CC(=C(C=C2)N=NC3=C(C4=C(C=C3)C(=CC(=C4N)S(=O)(=O)O)S(=O)(=O)O)O)OC)N=NC5=C(C6=C(C=C5)C(=CC(=C6N)S(=O)(=O)O)S(=O)(=O)O)O.[Na+] ORFSSYGWXNGVFB-UHFFFAOYSA-N 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- OWQUYBAASOSGNO-CDNKMLFNSA-N 2-[[(Z)-N-(2-hydroxy-5-sulfoanilino)-C-phenylcarbonimidoyl]diazenyl]benzoic acid Chemical compound C1=CC=C(C=C1)/C(=N/NC2=C(C=CC(=C2)S(=O)(=O)O)O)/N=NC3=CC=CC=C3C(=O)O OWQUYBAASOSGNO-CDNKMLFNSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 101100433727 Caenorhabditis elegans got-1.2 gene Proteins 0.000 description 1
- 206010013082 Discomfort Diseases 0.000 description 1
- 206010013952 Dysphonia Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000010473 Hoarseness Diseases 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 206010028748 Nasal obstruction Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 238000005266 casting Methods 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- -1 compound zinc gluconate Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000000205 computational method Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 239000008233 hard water Substances 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 239000008932 jinhong Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 208000010753 nasal discharge Diseases 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- CPJJXNTZFVBYIA-UHFFFAOYSA-M potassium boric acid chloride Chemical compound [Cl-].[K+].OB(O)O CPJJXNTZFVBYIA-UHFFFAOYSA-M 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 208000023409 throat pain Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000005723 virus inoculator Substances 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229940091251 zinc supplement Drugs 0.000 description 1
- 229940043798 zincon Drugs 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a zinc gluconate sugar tablet preparation and a preparation method thereof. The sugar tablet comprises the following components by mass: 93.24-160 parts of zinc gluconate and pharmaceutic excipients such as 1460-2500 parts of white sugar, 2910-5000 parts of maltose syrup or glucose syrup, 30-52 parts of glycine, 438-750 parts of purified water and 30-52 parts of fruit flavoring agents. The preparation is prepared by dissolving sugar at high temperature, boiling sugar under vacuum, etc. The form of the preparation is semi-transparent hard sugar tablet and the preparation is the buccal tablet. The sugar tablet is dissolved in the mouth, so that the zinc ions can permeate the nose, throat and susceptible tissues in the nasal sinus to be combined with the influenza virus receptor to prevent the influenza virus from further spreading among the cells so as to achieve the aims of treating cold and alleviating cold symptoms.
Description
Technical field
The present invention relates to a kind ofly treat flu, alleviate symptom zinc gluconate sugar-tablet pharmaceutical preparation of flu and preparation method thereof, belong to medical technical field.
Background technology
Flu is one of modal disease in the world, also is one of main public health problem of facing of the mankind.The annual sickness rate of flu is 10%-30% according to statistics, and all parts of the world all has thousands of people to infect every year.Life is almost had no talent and had not been suffered from flu, and symptom is: nasal obstruction, rhinorrhea, sneeze, cough, heating, systemic pain etc.If treatment is untimely bring out pharyngitis, otitis media, bronchitis, pneumonia, etc. disease.
The gluconic acid zinc preparation is in a large number as zinc supplement at home, the product that is used for the treatment of the flu aspect seldom, the zinc gluconate nasal spray that enterprise of domestic existing youngster family produces, because nasal spray is stronger to the nasal mucosa zest, and interrelated data report, use the zinc gluconate nasal spray may cause the permanent olfactory sensation that loses, the patient accepts difficulty clinically.
Chinese patent file CN1091638A (CN93101972.9) discloses a kind of anti-flu Xinkekang, principal agent is zinc gluconate, ibuprofen, chlorphenamine, be processed into tablet capsule or electuary, the direct gastrointestinal tract oral medication flu of the relevant zinc gluconate of report both at home and abroad curative effect is undesirable.
Chinese patent file CN1100306A (CN94103818.1) discloses compound zinc gluconate preparation of treatment flu and preparation method thereof, principal agent is zinc gluconate, ibuprofen, chlorphenamine, will make capsule, tablet, dissolved granule or buccal tablet with suitable pharmaceutic adjuvant.This buccal tablet mouthfeel bitterness because zinc gluconate discharges zinc ion rapidly in the oral cavity, has a kind of peculiar taste, and sense of taste is poor during containing, incompatibility patient's use.
Above invention technology is a compound preparation, contains chlorphenamine, and side effect such as drowsiness are arranged; Therefore the driver, operate machine or the work high above the ground personnel need careful usefulness.Because above various deficiencies make existing zinc gluconate cold-treating preparation product be very limited in clinical practice.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, provide a kind of treatment that is suitable for containing to catch a cold, alleviate the zinc gluconate sugar-tablet preparation method of cold symptoms.
Technical scheme of the present invention is as follows:
A kind of zinc gluconate sugar-tablet preparation, make by mass parts by following raw material:
A: zinc gluconate 93.24-160 part;
B: pharmaceutic adjuvant: white sugar 1460-2500 part, maltose syrup or glucose syrup (folding solid content) 2910-5000 part, purified water 438-750 part, glycine 30-52 part, fruit flavor agent 30-52 part.
Preferably, a kind of zinc gluconate sugar-tablet preparation, make by mass parts by following raw material:
A: zinc gluconate 93.24-120 part;
B: pharmaceutic adjuvant: white sugar 1460-1880 part, maltose syrup or glucose syrup (folding solid content) 2910-3750 part, purified water 438-565 part, glycine 30-39 part, an amount of 30-39 part of fruit flavor agent.
The preparation method of the zinc gluconate sugar-tablet preparation of the invention described above, step is as follows:
(1) it is standby to take by weighing the fruit flavor agent that zinc gluconate, glycine, white sugar, maltose syrup or glucose syrup, purified water and seasoning use by recipe quantity.
(2) in dissolving tank, add white sugar, maltose syrup or glucose syrup and purified water, open to stir, heat temperature raising to 80～90 ℃, it is dissolved fully after; Drop into zinc gluconate, glycine, continue to stir 10 minutes, after the dissolving, open vacuum pump fully, will dissolve in the vacuum sugar boiling of the liquid glucose suction completely vaporizer, 90～100 ℃ of vacuum sugar boiling vaporizer elder generation preheatings.
(3) the condenser recirculated water in the unlatching vacuum sugar boiling vaporizer is opened steam valve, and steam pressure is controlled at 0.4～0.6Mpa, heats up; Vacuum degree control is at 30～41kp, and the moisture of vacuum concentration liquid glucose when vacuum sugar cook temperature rises to 125～128 ℃, is stirred off and finished, and massecuite moisture content is controlled at below the 3wt%.
(4) massecuite that will boil is put into Mixer pot, is incubated 100～105 ℃, adds the seasoning fruit flavor agent, rubs up evenly.
(5) will rub up uniform massecuite temperature and be controlled at 70～80 ℃, and send into insulation and roll in the machine and be rolled into strip, and enter then and be drawn into evenly suitable sugared bar in the equal bar machine and enter in the stamping machine, pressure and the sheet of regulating stamping machine are heavy; Punch forming.
(6) sugar-tablet of stamping is cooled to room temperature after, sort, remove the damaged sugar-tablet of profile.
At last, full inspection, packing, warehouse-in.
Another preparation method of zinc gluconate sugar-tablet preparation of the present invention, step is as follows:
(1) takes by weighing the fruit flavor agent that zinc gluconate, glycine, white sugar, maltose syrup or glucose syrup (folding solid content) and seasoning are used.
(2) in dissolving tank, add white sugar, maltose syrup or glucose syrup and purified water, open to stir, heat temperature raising to 80～90 ℃, it is dissolved fully after; Drop into zinc gluconate, glycine, continue to stir 10 minutes, fully after the dissolving; Add the seasoning fruit flavor agent.Open vacuum pump, will dissolve in the vacuum sugar boiling of the liquid glucose suction completely vaporizer, 90～100 ℃ of vacuum sugar boiling vaporizer elder generation preheatings.
(3) the condenser recirculated water in the unlatching vacuum sugar boiling vaporizer is opened steam valve, and steam pressure is controlled at 0.4～0.6Mpa, heats up; Vacuum degree control is at 30～41kp, and the moisture of vacuum concentration liquid glucose when vacuum sugar cook temperature rises to 125～128 ℃, is stirred off and finished, and massecuite moisture content is controlled at below the 3wt%.
(4) will boil liquid massecuite temperature and be controlled at 105～110 ℃ and quantitatively be poured in the model, pass through cooling tunnel; Be cooled to room temperature, typing.
(5) cooling and shaping is good sugar-tablet sorts, and removes the damaged sugar-tablet of profile.
At last, full inspection, packing, warehouse-in.
Zinc gluconate sugar-tablet of the present invention pharmaceutical preparation, the employing zinc gluconate is an effective ingredient, with the pharmaceutic adjuvant of selected preparation by high temperature sugar, vacuum sugar boiling, be in harmonious proportion, tie rod, punching press, molding or by high temperature sugar, vacuum sugar boiling, cast, cooling, molding is made, the products obtained therefrom dosage form is translucent hard sugar sheet, wherein in the present invention, add the correctives glycine, zinc ion complexation in glycine and the zinc gluconate, in the oral cavity, slowly discharge zinc ion, avoided the metal sense of taste of zinc ion on the one hand, clinical effect continues slowly to discharge zinc ion and prolongs the drug effect purpose to reach on the other hand, so mouthfeel is good, makes that people are more glad to take.Through the buccal administration, sugar-tablet passes through buccal, zinc ion can be infiltrated in nose, pharynx and the sensitive organization of nasal sinuses portion and the cold virus receptors bind, make the zinc ion in nose, pharynx, the nasal sinuses portion mucosa form barrier one, stop cold virus to reach the purpose that treatment is caught a cold, alleviated the symptom of flu in the further diffusion of iuntercellular.
Above-mentioned preparation method gained zinc gluconate sugar-tablet of the present invention is quality controllable.
Zinc gluconate sugar-tablet quality standard is following but do not limit the following stated zinc gluconate sugar-tablet standard in the preparation method of the present invention.
Zinc gluconate sugar-tablet quality standard
This product contains zinc gluconate (C
12H
22O
14Zn) should be 93.0%～107.0% of labelled amount.
[character] this product character is orange or translucent of brown, and it is sweet to distinguish the flavor of.
1 of this product (being equivalent to zinc gluconate 0.1g approximately) is got in [discriminating] (1), add water 50ml dissolving after, add 1 of ferric chloride test solution, should show buff.
(2) aqueous solution of this product shows the identification of zinc salt, according to " Chinese Pharmacopoeia 2010 version two ones (appendix III) "
[inspection] uniformity of dosage units is got 1 of this product, put in the 250ml conical flask, add water 100ml, the slight fever dissolving, ammonification-ammonium chloride buffer (pH10.0) 5ml and ammonium fluoride 0.5g, the dissolving, add again chromium black T indicator a little, change pure blue with Calcium Disodium Versenate volumetric solution (0.05mol/L) titration to solution into from aubergine.Every 1ml Calcium Disodium Versenate volumetric solution (0.05mol/L) is equivalent to the C of 22.78mg
12H
22O
14Zn.Should be up to specification " Chinese Pharmacopoeia 2010 version two ones (appendix XE) ".
Dissolution is got this product, according to " two (appendix XC) second methods of Chinese Pharmacopoeia version in 2010 ", is dissolution medium with water 1000ml, and rotating speed is that per minute 75 changes ± 5 commentaries on classics, operation in accordance with the law, and in the time of 30 minutes, it is an amount of to get solution, filters, and gets subsequent filtrate as need testing solution; Other gets the about 50mg of zinc gluconate reference substance that is dried to constant weight, and accurate the title decides, and adds water and makes dissolving in right amount and be diluted to 1000ml, product solution in contrast.Precision is measured need testing solution 3ml and reference substance solution 5ml, put respectively in the 50ml measuring bottle, after respectively adding boric acid potassium chloride buffer (pH9.0) 10ml, the accurate zinc test solution that adds new preparation (is got zincon 0.13g, after adding 1mol/L sodium hydroxide solution 2ml dissolving, add water and make into 100ml) 3ml, shake up, be diluted with water to scale, shake up, according to " Chinese Pharmacopoeia 2000 version two ones (appendix IVA) " spectrophotography, wavelength place at 620nm measures absorbance, calculate every stripping quantity, limit is 75% of a labelled amount, should be up to specification.
Other should meet every regulation relevant under the tablet item " Chinese Pharmacopoeia 2010 version two ones (appendix I A) ".
[assay] gets 20 of this product, the accurate title, decide, get wherein any 3 (being equivalent to zinc gluconate 0.3g approximately) then, accurate again title is fixed, and adding water 100ml, slight fever is dissolved, ammonification-ammonium chloride buffer (pH10.0) 5ml and ammonium fluoride 0.5g, add again chromium black T indicator a little, change pure blue with Calcium Disodium Versenate volumetric solution (0.05mol/L) titration to solution into from aubergine.Every 1ml Calcium Disodium Versenate volumetric solution (0.05mol/L) is equivalent to the C of 22.78mg
12H
22O
14Zn.
Zinc gluconate sugar-tablet preparation safety of the present invention, efficient, quality controllable, easy to use, no matter to compare with existing zinc gluconate cold medicine be prescription, dosage form to this sugar-tablet, or significant distinctive feature is arranged all in preparation method.Be specially:
1, do not contain chlorphenamine in the zinc gluconate sugar-tablet pharmaceutical formulation of the present invention, the patient takes the no drowsiness property in back, and the people that are fit to various working environments use.
2, add the correctives glycine among the present invention, zinc ion complexation in glycine and the zinc gluconate, slowly discharge zinc ion in the oral cavity, avoided the metal sense of taste of zinc ion on the one hand, clinical effect continues slowly to discharge zinc ion and prolongs the drug effect purpose to reach on the other hand; The dosage form of zinc gluconate sugar-tablet preparation is translucent hard sugar sheet, and good looking appearance, mouthfeel is good, compliance is strong, the patient be willing to accept, and is particularly suitable for old man and child and uses.
3, zinc gluconate sugar-tablet of the present invention passes through buccal, make zinc ion can infiltrate nose, pharynx and sensitive organization of nasal sinuses portion and combine with the ICAM-1 virus receptor, zinc ion in nose, pharynx, the nasal sinuses portion mucosa has formed barrier one like this, stops cold virus to reach the purpose that treatment is caught a cold, alleviated the symptom of flu in the further diffusion of iuntercellular.
Description of drawings
Fig. 1 is the clinical efficacy contrast of zinc gluconate sugar-tablet of the present invention and ribavirin buccal tablet, and the zinc gluconate sugar-tablet is the product of embodiment 4, referring to embodiment 8.
The specific embodiment
The present invention is described further below in conjunction with embodiment, but be not limited thereto.
The supplementary material source is described as follows among the embodiment:
Zinc gluconate: the Shanghai moral wins pharmaceutical Co. Ltd of scientific and technological group (Anqing).
White sugar: Hunan Er-kang Pharmaceutical Co., Ltd..
Purified water: Shandong Sibangde Pharmaceutical Co., Ltd..
Glycine: the flourish aminoacid company limited in Ji, Jinzhou, above supplementary material all meets Chinese Pharmacopoeia version two ministerial standards in 2010.
Maltose syrup, glucose syrup: continent, Shandong biotechnology (Shandong) company limited.Meet national standard (GB/T20883-2007), (GB/T 20885-2007).
Fruit flavor agent: Beijing Powdery Food Co., Ltd. meets national standard (GB2760-2007).
Device and equipment related among the embodiment are hard water fructose production common apparatus, and market can be purchased.Be described as follows:
Dissolving tank 200L: Shandong Xinhua medical apparatus and instruments company limited.
A machine (model GCH150), equal bar machine (model DHJT40) are rolled in vacuum sugar boiling vaporizer (model ELGA200), Mixer pot (model EYT150), insulation: the East Sea, Ningbo machine-building company limited.
Stamping machine (model C YJ1000), casting molding machine (model JH-880): Ningbo East Sea Machinery Co., Ltd..
Cooling tunnel (model TLQ-WJD450): Chengdu Tian Wang food industry company.
Sorter (model FJ150): the permanent food machinery factory of containing in Qingzhou, Shandong.
Packer (model JH-880): WENLING JINHONG FOOD MACHINERYCO.,LTD.
The preparation of embodiment 1, zinc gluconate sugar-tablet
1, raw and auxiliary material inventory proportioning:
Zinc gluconate: white sugar: maltose syrup: glycine: fruit flavor agent: purified water=93.24: 1460: 2910 (folding solid content): 30: 30: 438 (mass ratio W/W)
2, preparation method, step is as follows:
(1) it is standby to take by weighing the fruit flavor agent 0.6kg that zinc gluconate 1.865kg, glycine 0.6kg, white sugar 29.2kg, maltose syrup 58.2kg (folding solid content), purified water 8.76kg and seasoning use by recipe quantity.
(2) in dissolving tank, add and taken by weighing white sugar, maltose syrup and purified water, open and stir, heat temperature raising to 80～90 ℃, it is dissolved fully after; Drop into standby zinc gluconate, glycine, continue to stir 10 minutes, fully after the dissolving.Open vacuum pump, will dissolve (90～100 ℃ of first preheatings) in the vacuum sugar boiling of the liquid glucose suction completely vaporizer.
(3) the condenser recirculated water in the unlatching vacuum sugar boiling vaporizer is opened steam valve, and steam pressure is controlled at 0.4～0.6Mpa, heats up; Vacuum degree control is at 30～41kp, and the moisture of vacuum concentration liquid glucose when vacuum sugar cook temperature rises to 125～128 ℃, is stirred off and finished, and massecuite moisture content is controlled at below 3% (W/W).
(4) massecuite that will boil is put into Mixer pot, is incubated 100～105 ℃, adds the seasoning fruit flavor agent, rubs up evenly.
(5) will rub up uniform massecuite temperature and be controlled at 70～80 ℃, send into to be incubated to roll in the machine and be rolled into strip, enter then and be drawn into evenly suitable sugared bar in the equal bar machine and enter in the stamping machine, pressure and the sheet of regulating stamping machine heavily are 4.5g/ sheet (containing zinc gluconate 93.24mg/ sheet); Punch forming.
(6) behind the sugar-tablet cooling room temperature with stamping, enter in the sorter, remove the damaged sugar-tablet of profile.
At last, examine entirely, pack, put in storage.Batch number: 20100301.
The preparation of embodiment 2, zinc gluconate sugar-tablet
1, raw and auxiliary material inventory proportioning:
Zinc gluconate: white sugar: maltose syrup: glycine: fruit flavor agent: purified water=93.24: 1880: 3750 (folding solid content): 39: 39: 565 (mass ratio W/W)
2, preparation method, step is as follows:
1) it is standby to take by weighing the fruit flavor agent 0.78kg that zinc gluconate 1.865kg, glycine 0.78kg, white sugar 37.6kg, maltose syrup 75kg (folding solid content), purified water 11.3kg and seasoning use by recipe quantity.
2) in dissolving tank, add and taken by weighing white sugar, maltose syrup and purified water, open and stir, heat temperature raising to 80～90 ℃, it is dissolved fully after; Drop into standby zinc gluconate, glycine, continue to stir 10 minutes, fully after the dissolving; Add the seasoning fruit flavor agent.Open vacuum pump, will dissolve (90～100 ℃ of first preheatings) in the vacuum sugar boiling of the liquid glucose suction completely vaporizer.
3) the condenser recirculated water in the unlatching vacuum sugar boiling vaporizer is opened steam valve, and steam pressure is controlled at 0.4～0.6Mpa, heats up; Vacuum degree control is at 30～41kp, and the moisture of vacuum concentration liquid glucose when vacuum sugar cook temperature rises to 125～128 ℃, is stirred off and finished, and massecuite moisture content is controlled at below 3% (W/W).
4) will boil liquid massecuite temperature and be controlled at 105～110 ℃ and quantitatively be poured in the model, sheet heavily is 5.8g/ sheet (containing zinc gluconate 93.24mg/ sheet), passes through cooling tunnel; The typing of cooling room temperature.
5) cooling and shaping is good sugar-tablet enters in the sorter, removes the damaged sugar-tablet of profile.
At last, examine entirely, pack, put in storage.Batch number: 20100302.
The preparation of embodiment 3, zinc gluconate sugar-tablet
1, raw and auxiliary material inventory proportioning:
Zinc gluconate: white sugar: glucose syrup: glycine: fruit flavor agent: purified water=93.24: 1670: 3330 (folding solid content): 35: 35: 502 (mass ratio W/W)
2, preparation method, step is as follows:
(1) it is standby to take by weighing the fruit flavor agent 0.7kg that zinc gluconate 1.865kg, glycine 0.7kg, white sugar 33.4kg, glucose syrup 66.6kg (folding solid content), purified water 10kg and seasoning use by recipe quantity.
(2)～(4) operation is identical with corresponding steps (2)～(4) of embodiment 1.
(5) will rub up uniform massecuite temperature and be controlled at 70～80 ℃, send into to be incubated to roll in the machine and be rolled into strip, enter then and be drawn into evenly suitable sugared bar in the equal bar machine and enter in the stamping machine, pressure and the sheet of regulating stamping machine heavily are 5.2g/ sheet (containing zinc gluconate 93.24mg/ sheet); Punch forming.
(6) behind the sugar-tablet cooling room temperature with stamping, enter in the sorter, remove the damaged sugar-tablet of profile.
At last, examine entirely, pack, put in storage.Batch number: 20100303.
The preparation of embodiment 4, zinc gluconate sugar-tablet
1, raw and auxiliary material inventory proportioning:
Zinc gluconate: white sugar: glucose syrup: glycine: fruit flavor agent: purified water=93.24: 1565: 3120 (folding solid content): 33: 33: 470 (mass ratio W/W).
2, preparation method, step is as follows:
(1) it is standby to take by weighing the fruit flavor agent 0.66kg that zinc gluconate 1.865kg, glycine 0.66kg, white sugar 31.3kg, glucose syrup 62.4kg (folding solid content), purified water 9.4kg and seasoning use by recipe quantity.
(2)～(3) operation is identical with corresponding steps (2)～(3) of embodiment 2.
(4) will boil liquid massecuite temperature and be controlled at 105～110 ℃ and quantitatively be poured in the model, sheet heavily is 4.8g/ sheet (containing zinc gluconate 93.24mg/ sheet), passes through cooling tunnel; Be cooled to the room temperature typing.
(5) cooling and shaping is good sugar-tablet enters in the sorter, removes the damaged sugar-tablet of profile.
At last, examine entirely, pack, put in storage.Batch number: 20100304.
1, test material
(1) medicine: zinc gluconate sugar-tablet, the zinc gluconate sugar-tablet (lot number 20100301) of embodiment 1 preparation, every weight 4.5g (containing zinc gluconate 93.24mg/ sheet); Place mortar to be ground into fine grained; Stand-by.
Excipient (blank sugar-tablet): with the adjuvant of embodiment 1, the preparation method of pressing embodiment 1 does not add zinc gluconate, and the translucent blank sugar-tablet that makes places mortar to be ground into fine grained, and is stand-by.
(2) animal: Golden Hamster, grade are regular grade, are provided by Shandong University's Experimental Animal Center, and 24 male, body weight 120g ± 20g.
2, oral mucosa irritation test method
Grouping: get 24 of fasting 12h Golden Hamster, be divided into zinc gluconate sugar-tablet intact mucosa group at random, the damaged mucosa group of zinc gluconate sugar-tablet, excipient (blank sugar-tablet) intact mucosa group, the damaged mucosa group of excipient (blank sugar-tablet), 6 every group by body weight.The contrast of self left and right sides mucosa, the left side administration, the right side is as blank.The aseptic pin of 24h scratches mucosa group Golden Hamster left and right sides mouth cheek mucosa before the administration.
Administration: Golden Hamster is got dorsal position fix, zinc gluconate sugar-tablet group is got accurate weighing zinc gluconate sugar-tablet 16mg and is put into its left side, oral cavity cheek pouch, and excipient (blank sugar-tablet) group is got excipient 16mg and put into its left side, oral cavity cheek pouch.Administration every day 3 times, continuous 3d, zinc gluconate sugar-tablet observe and estimate and Histological evaluation the zest of Golden Hamster oral mucosa.
The tissues observed morphological change is marked by table 1 under the optical frames;
The mucosa that observation and record contact with medicine has or not erythema, erosion and edema etc. to mark by table 2;
Table 1. oral cavity tissue reaction microscope standards of grading
Table 2: oral stimulation reaction standards of grading
(1) at duration of test, all animal activities are normal, and diet is normal, does not see systemic adverse reactions.Each test group is not seen oral mucosa hyperemia, hemorrhage, erosion or ulcer.Each organizes 1: 3 chamber mucosa of administration side and control sides is not seen difference, and zinc gluconate sugar-tablet group and excipient (blank sugar-tablet) group is not seen difference.By oral stimulation reaction standards of grading, each treated animal score sees Table 3.
Table 3 oral stimulation reaction scoring
The result: gross examination of skeletal muscle shows oral cavity intact mucosa and the damaged mucosa equal nonirritant of zinc gluconate sugar-tablet to Golden Hamster; Histopathologic examination shows that the zinc gluconate sugar-tablet does not all produce pathological changes such as inflammation to intact mucosa and damaged mucosa; The histopathology scoring shows that the zinc gluconate sugar-tablet is to intact mucosa and the equal nonirritant of damaged mucosa.
(2) histological observation evaluation: pathology are evaluated as biopsy of oral mucosa: each group of intact mucosa is carried out microscopy, observe pathological states such as its mucosal epithelium, inflammatory cell infiltration, vascular reaction and interstitial edema, find 4 groups of no significant differences, prompting zinc gluconate sugar-tablet is to the pathological changes such as oral cavity intact mucosa NIP stimulation of Golden Hamster; Each group of damaged mucosa is carried out microscopy, observe its mucosal epithelium, inflammatory cell infiltration, vascular reaction and ask pathological states such as matter edema, find 4 groups of no significant differences, point out the pathological changes such as oral cavity intact mucosa NIP stimulation of zinc gluconate sugar-tablet to Golden Hamster: other has the discovery of observation, in the damaged mucosal drug delivery group of zinc gluconate sugar-tablet, have to show under the 4 routine mirrors that Submucosa has good granulation tissue to form, prompting zinc gluconate sugar-tablet has certain facilitation to the repair process of the damaged mucosa in oral cavity.Press oral cavity tissue reaction microscopic evaluation categorizing system, judge that each treated animal score sees Table 4.
The scoring of table 4 oral cavity tissue reaction microscope
| Grouping | Number of animals | The accumulative total stimulation index | Irritant reaction |
| Zinc gluconate sugar-tablet intact mucosa group | 6 | 0 | Nonirritant |
| The damaged mucosa group of zinc gluconate sugar-tablet | ?6 | 0 | Nonirritant |
| Excipient (blank) intact mucosa group | ?6 | 0 | Nonirritant |
| The damaged mucosa group of excipient (blank) | ?6 | 0 | Nonirritant |
Conclusion: the zinc gluconate sugar-tablet is to the oral mucosa nonirritant of Golden Hamster, therefore, the zinc gluconate sugar-tablet in treatment treatment flu, to alleviate aspect the symptom of flu be safe.
Embodiment 6, zinc gluconate sugar-tablet are to acute toxicity test in mice
1, test material
(1) medicine: with the zinc gluconate sugar-tablet of embodiment 3 preparations; Test lot number 20100303, every weight 5.2g (containing zinc gluconate 93.24mg/ sheet).Get 30 of the zinc gluconate sugar-tablets of embodiment 3 preparation, porphyrize, with dissolved in distilled water and be diluted to 225ml, this solution contains the gluconic acid zinc concentration and is 0.0124g/ml, and is stand-by.
(2) animal: Kunming kind white mice, body weight 19.5g ± 1.0g.Male and female half and half, grade are regular grade; Provide by Shandong University's Experimental Animal Center.
2, test method
Because mouse stomach LD
50Do not measure, do the mensuration of mice maximum tolerated dose.Get 20 of 12 hours mices of fasting (can't help water), male and female half and half.To be mixed with zinc gluconate sugar-tablet solution and give mouse stomach respectively, the administration volume is 0.8ml/20g, three times on the one, each 8 hours at interval, observes continuously 7 days.
Result of the test: in high spirits after the mice administration, the hair glossy, activity freely, two is just normal, weight increase, no abnormality seen and death.The mouse stomach dosage is calculated as follows the multiple of maximum tolerated dose and quite clinical adult's medication.The results are shown in Table 5.
Mice maximum tolerated dose every day computational methods:
(the computing formula explanation: become body weight for humans to count according to average 60kg, it is 6 that the adult takes medicine every day).
Table 5 mice maximum tolerance determination result
Conclusion: because mouse stomach LD
50Do not measure, so do the dosis tolerata of Cmax, maximum volume measures to mice, the zinc gluconate sugar-tablet is to the mice maximum tolerated dose: only gavage zinc gluconate sugar-tablet solution (Cmax 0.0124g/ml) 0.8ml/ each time, three times on the one, every day, the accumulative total dosage was 0.0298g/, quite about 160 times of the clinical consumption of adult, observed continuously 7; And mice does not have any unusual, and also none is only dead, proves that zinc gluconate sugar-tablet toxicity is very low; Clinical drug safety.
Embodiment 7, zinc gluconate sugar-tablet are to the protection of mice influenza infection
1, test material
(1) medicine: the zinc gluconate sugar-tablet is tested lot number 20100302, every weight 5.8g (containing zinc gluconate 93.24mg/ sheet) with the zinc gluconate sugar-tablet of embodiment 2 preparations.
The preparation of trial drug: get 30 of the zinc gluconate sugar-tablets (test lot number 20100302) of embodiment 2 preparations, place mortar to be ground into fine grained, stand-by.
Blank sugar-tablet: with the identical adjuvant of embodiment 2, the preparation method of press embodiment 2 does not add the translucent blank sugar-tablet that zinc gluconate prepares.
Test the preparation of blank sugar-tablet: get 30 of blank sugar-tablets, place mortar to be ground into fine grained, stand-by.
(2) influenza virus Mus lung adapted strain FM1, Shandong Medical University microbe research chamber provides;
Embryo Gallus domesticus 9 days is provided by chicken farm, Weifang, Shandong;
Animal: Kunming kind white mice, body weight 19.5g ± 1.0g, 40 male and female half and half, grade are regular grade; Provide by Shandong University's Experimental Animal Center.
2, test method:
Influenza virus: virus inoculation is gathered in the crops allantoic fluid at 35 ℃ after hatching 48 hours in 6 Embryo Gallus domesticus, measure tiring of allantoic fluid in 6 Embryo Gallus domesticus with the blood clotting method after, merge as stock solution-80 ℃ of preservations.
The zinc gluconate sugar-tablet is to the protection of mice influenza infection: get 40 of mices, be divided into 4 groups at random, every group 10, excipient (blank sugar-tablet) is a matched group, the zinc gluconate sugar-tablet be divided into 3 groups (high dose group 150mg/ only, middle dosage group 75mg/ only, low dose group 37.5mg/ only), each group infects with viral dilution liquid (virus stock solution used 10-1 concentration) 30ul collunarium under the shallow fiber crops of ether, after 2 hours; The administration group respectively at the mice oral cavity give high dose 150mg/ only, middle dosage 75mg/ only, low dosage 37.5mg/ three kinds of dosage zinc gluconate sugar-tablets only.Excipient (blank sugar-tablet) matched group (pressing a high dose 150mg/ administration) is by last method operation.Altogether administration 6 day every day 6 times, each 2 hours at interval, observed 15 days after the administration.The death toll and the time of writing down mice every day see Table 6.
Death toll of table 6. mice and time
The result: the high, medium and low dosage of zinc gluconate sugar-tablet all can obviously prolong mouse diing time and mortality rate.
Embodiment 8, the preliminary clinical trial of zinc gluconate sugar-tablet
1, test material
(1) medicine: the zinc gluconate sugar-tablet that the zinc gluconate sugar-tablet prepares with embodiment 4; Test lot number 20100304, every weight 4.8g (containing zinc gluconate 93.24mg/ sheet);
The ribavirin buccal tablet: Shandong Lvyin Pharmaceutical Co., Ltd, specification is 50mg/ sheet (the accurate word H37024023 of traditional Chinese medicines);
(2) study subject: this test comprises 60 study subjects, random packet altogether; Summary to these study subjects sees Table 7.
Result of the test is: (N=59) 98.3% experimenter has finished test; Wherein ribavirin buccal tablet group (n=1 1.7%) 1 example is dropped by the wayside, and reason is share the other treatment cold medicine; The patient recalls informed consent, amounts to 59 and finishes test.
The experimenter personnel of table 7. test
2, test method
(1) inclusion criteria: meet the flu diagnostic criteria: in the cold symptoms such as having a stuffy nose appears in the patient, sneeze, watery nasal discharge, throat pain, cough, hoarseness 2 and more than, can be with symptoms such as heating, headache, systemic pain, weak discomforts; Get rid of the above-mentioned symptom that other diseases causes; The patient need satisfy above 3 conditions simultaneously; Occur in above-mentioned symptom 24～48h; 12～20 years old age, male or female, the experimenter of voluntary participation also signs written Informed Consent Form.
(2) take requirement: all qualified experimenters accept every day 6 times during this period, and each 1, each treatment in 2 hours at interval; Flu patient containing sugar-tablet (must not chew or swallow) during clinical must not eat citrus fruit or fruit juice in the half an hour before or after buccal.
(3) clinical indexes
All selected objects are made physical examination by experienced clinicist's detailed medical history-taking, and in time are recorded in " in the clinical trial patient chart (CRF) ".
Observe and write down experimenter's symptom, sign situation of change every day.Duration of test itemized record diet situation, no special circumstances do not change dietary habit, have no adverse reaction in close observation and the recording medicine process.See Table 8
Table 8. scoring that observes the symptoms
Result: pass through controlled clinical trial, add up according to table 8 pair cold symptoms total mark, throw off a cold the time according to total mark calculating, always have 59 flu patients and finally reach evaluation criteria (all cold symptoms disappear), its average cold symptoms course of disease of zinc gluconate sugar-tablet group is 4 ± 2.1 days, the average cold symptoms course of disease of ribavirin buccal tablet group is 4 ± 2.2 days, 2 groups of comparing difference not statistically significants (P＞0.05), show 2 kinds of clinical drug curative effect unanimities, be the active drug that treatment is caught a cold, alleviated cold symptoms.See the curative effect comparision of Fig. 1 zinc gluconate sugar-tablet and ribavirin buccal tablet.
Claims (4)
1. zinc gluconate sugar-tablet preparation is characterized in that being made by mass parts by following raw material:
A: zinc gluconate 93.24-160 part;
B: pharmaceutic adjuvant: white sugar 1460-2500 part, maltose syrup or glucose syrup 2910-5000 (folding solid content) part, glycine 30-52 part, purified water 438-750 part, fruit flavor agent 30-52 part.
2. zinc gluconate sugar-tablet preparation as claimed in claim 1 is characterized in that being made by mass parts by following raw material:
A: zinc gluconate 93.24-120 part;
B: pharmaceutic adjuvant: white sugar 1460-1880 part, maltose syrup or glucose syrup 2910-3750 (folding solid content) part, 3039 parts of glycine, purified water 438-565 part, fruit flavor agent 30-39 part.
3. the preparation method of claim 1 or 2 described zinc gluconate sugar-tablet preparations, step is as follows:
(1) it is standby to take by weighing zinc gluconate, glycine, white sugar, maltose syrup or glucose syrup and fruit flavor agent;
(2) in dissolving tank, add white sugar, maltose syrup and purified water, open to stir, heat temperature raising to 80～90 ℃, it is dissolved fully after; Drop into zinc gluconate, glycine, continue to stir 10 minutes, fully after the dissolving; Open vacuum pump, will dissolve in the vacuum sugar boiling vaporizer of 90～100 ℃ of the first preheatings of liquid glucose suction completely;
(3) the condenser recirculated water in the unlatching vacuum sugar boiling vaporizer is opened steam valve, and steam pressure is controlled at 0.4～0.6Mpa, heats up; Vacuum degree control is at 30～41kp, and the moisture of vacuum concentration liquid glucose when vacuum sugar cook temperature rises to 125～128 ℃, is stirred off and finished, and massecuite moisture content is controlled at below 3% (W/W);
(4) massecuite that will boil is put into Mixer pot, is incubated 100～105 ℃, adds the seasoning fruit flavor agent, rubs up evenly;
(5) will rub up uniform massecuite temperature and be controlled at 70～80 ℃, and send into insulation and roll in the machine and be rolled into strip, and enter then and be drawn into evenly suitable sugared bar in the equal bar machine and enter in the stamping machine, pressure and the sheet of regulating stamping machine are heavy; Punch forming;
(6) behind the sugar-tablet cooling room temperature with stamping, sort.
4. the preparation method of claim 1 or 2 described zinc gluconate sugar-tablet preparations, step is as follows:
1) standby by taking by weighing zinc gluconate, glycine, white sugar, maltose syrup or glucose syrup and fruit flavor agent.
2) in dissolving tank, add white sugar, maltose syrup and purified water, open to stir, heat temperature raising to 80～90 ℃, it is dissolved fully after; Drop into zinc gluconate, glycine, continue to stir 10 minutes, fully after the dissolving; Add the seasoning fruit flavor agent.Open vacuum pump, will dissolve in the vacuum sugar boiling vaporizer of 90～100 ℃ of the first preheatings of liquid glucose suction completely;
3) the condenser recirculated water in the unlatching vacuum sugar boiling vaporizer is opened steam valve, and steam pressure is controlled at 0.4～0.6Mpa, heats up; Vacuum degree control is at 30～41kp, and the moisture of vacuum concentration liquid glucose when vacuum sugar cook temperature rises to 125～128 ℃, is stirred off and finished, and massecuite moisture content is controlled at below 3% (W/W);
4) will boil liquid massecuite temperature and be controlled at 105～110 ℃ and quantitatively be poured in the model, pass through cooling tunnel; The typing of cooling room temperature;
5) cooling and shaping is good sugar-tablet sorts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102852065A CN101961321B (en) | 2010-09-17 | 2010-09-17 | Zinc gluconate sugar tablet preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102852065A CN101961321B (en) | 2010-09-17 | 2010-09-17 | Zinc gluconate sugar tablet preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101961321A true CN101961321A (en) | 2011-02-02 |
| CN101961321B CN101961321B (en) | 2012-03-28 |
Family
ID=43514499
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102852065A Active CN101961321B (en) | 2010-09-17 | 2010-09-17 | Zinc gluconate sugar tablet preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101961321B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102422963A (en) * | 2011-10-09 | 2012-04-25 | 云南省玉溪市甜馨食品有限责任公司 | Passionflower fruit pie and its processing method |
| CN103271900A (en) * | 2013-05-31 | 2013-09-04 | 河南创新药业有限公司 | Zinc citrate tablet and preparation method thereof |
| CN103272224A (en) * | 2013-06-26 | 2013-09-04 | 乔敏 | Lysozyme sugar lozenge and preparation method thereof |
| CN103932985A (en) * | 2014-04-14 | 2014-07-23 | 山东司邦得制药有限公司 | Zinc gluconate oral spray and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1185316A (en) * | 1996-12-19 | 1998-06-24 | 张卫民 | Medicinal preparation containing saccharin zinc |
| WO2004110463A1 (en) * | 2003-06-06 | 2004-12-23 | The Procter & Gamble Company | Compositions for prevention and treatment of cold and influenza-like symptoms comprising chelated zinc |
-
2010
- 2010-09-17 CN CN2010102852065A patent/CN101961321B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1185316A (en) * | 1996-12-19 | 1998-06-24 | 张卫民 | Medicinal preparation containing saccharin zinc |
| WO2004110463A1 (en) * | 2003-06-06 | 2004-12-23 | The Procter & Gamble Company | Compositions for prevention and treatment of cold and influenza-like symptoms comprising chelated zinc |
Non-Patent Citations (1)
| Title |
|---|
| 《中国现代应用药学》 19850630 周永熊 锌能有效地减轻感冒症状 第40-41页 1-4 第02卷, 第03期 2 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102422963A (en) * | 2011-10-09 | 2012-04-25 | 云南省玉溪市甜馨食品有限责任公司 | Passionflower fruit pie and its processing method |
| CN103271900A (en) * | 2013-05-31 | 2013-09-04 | 河南创新药业有限公司 | Zinc citrate tablet and preparation method thereof |
| CN103271900B (en) * | 2013-05-31 | 2014-12-17 | 河南创新药业有限公司 | Zinc citrate tablet and preparation method thereof |
| CN103272224A (en) * | 2013-06-26 | 2013-09-04 | 乔敏 | Lysozyme sugar lozenge and preparation method thereof |
| CN103932985A (en) * | 2014-04-14 | 2014-07-23 | 山东司邦得制药有限公司 | Zinc gluconate oral spray and preparation method thereof |
| CN103932985B (en) * | 2014-04-14 | 2016-02-10 | 山东司邦得制药有限公司 | zinc gluconate oral spray and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101961321B (en) | 2012-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20170258861A1 (en) | Treatment of Herpes, Pseudomonas, Staph, and Hepatitis | |
| CN103784933B (en) | Recurrent oral ulceration falls apart | |
| CN102836228B (en) | Chinese medicinal composition for treating conjunctivitis and preparation method and application thereof | |
| CN101961321A (en) | Zinc gluconate sugar tablet preparation and preparation method thereof | |
| CN105380918B (en) | It is a kind of with blood sugar reducing health function acanthopanax trifoliatus polysaccharide tablet and preparation method thereof | |
| CN106109564A (en) | Pharmaceutical composition for the treatment of cerebral thrombosis and preparation method thereof | |
| CN105535406A (en) | Traditional Chinese medicine composition for preventing and treating livestock respiratory disease | |
| CN103932985B (en) | zinc gluconate oral spray and preparation method thereof | |
| CN1966051B (en) | Antivirus medicament for resisting virus | |
| CN100435817C (en) | Medicine for treating rheumatism and rheumatoid diseases and preparing method | |
| CN103272224A (en) | Lysozyme sugar lozenge and preparation method thereof | |
| CN112826849A (en) | Compound traditional Chinese medicine with broad-spectrum antibacterial, anti-inflammatory and antiviral effects and preparation method thereof | |
| CN102205045A (en) | Compound pharmaceutical composition for treating upper airway cough syndrome and preparation method as well as application thereof | |
| CN105147709A (en) | Novel application of tenofovir disoproxil fumarate or medicinal salt thereof | |
| CN101371861A (en) | High-efficient antiviral medicament composition in chickweed as well as preparation method and use thereof | |
| CN102973657A (en) | Scutellaria baicalensis, manchurian lilac bark and dahurian rhododendron leaf cough-arresting mixture and preparation method thereof | |
| CN103656267B (en) | A kind of Chinese medicine composition that is used for the treatment of pig blue-ear disease and its preparation method and application | |
| CN111053848A (en) | Traditional Chinese medicine composition for conditioning heat accumulation constitution of children and preparation method thereof | |
| CN104606225B (en) | A kind of anti-inflammation traditional Chinese herb medicine and preparation method thereof and quality control method | |
| CN115282243B (en) | Traditional Chinese medicine composition for treating pediatric acute bronchitis and preparation method thereof | |
| Hao et al. | Eucommia folium can be prepared into tea with the ability to prevent and treat hyperuricemia | |
| CN114699481B (en) | Traditional Chinese medicine for treating sore throat and preparation method thereof | |
| CN107970237A (en) | Imrecoxib is preparing the application in treating pulmonary fibrosis medicine | |
| CN108524488A (en) | A kind of pharmaceutical composition containing effective component in red sage and its granule preparation method and application | |
| CN101244170B (en) | Medicament for treating children's exogenous cough and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: SHANDONG SIBANGDE PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: JUREN BIOLOGICAL MEDICINES TECH. RESEARCH INST., SHANDONG Effective date: 20111231 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent of invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Qiao Min Inventor after: Yuan Wujie Inventor after: Xu Yan Inventor after: Liu Gang Inventor after: Teng Xuehou Inventor before: Teng Xuehou Inventor before: Qiao Min |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: TENG XUEHOU QIAO MIN TO: QIAO MIN YUAN WUJIE XU YAN LIU GANG TENG XUEHOU Free format text: CORRECT: ADDRESS; FROM: 250104 JINAN, SHANDONG PROVINCE TO: 250216 JINAN, SHANDONG PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20111231 Address after: 250216 Longshan office, Longhu Road, Shandong, Zhangqiu Applicant after: SHANDONG SIBANGDE PHARMACEUTICAL Co.,Ltd. Address before: 250104 Shandong Province, Ji'nan city high tech Development Zone Shun Road Shun Tai Plaza Building 9, room 1018 Applicant before: SHANDONG JUREN BIOPHARMACEUTICAL TECHNOLOGY Research Institute |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C53 | Correction of patent of invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Qiao Min Inventor after: Yuan Wujie Inventor after: Xu Yan Inventor after: Yang Yijuan Inventor after: Liu Gang Inventor after: Teng Xuehou Inventor before: Qiao Min Inventor before: Yuan Wujie Inventor before: Xu Yan Inventor before: Liu Gang Inventor before: Teng Xuehou |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: QIAO MIN YUAN WUJIE XU YAN LIU GANG TENG XUEHOU TO: QIAO MIN YUAN WUJIE XU YAN YANG YIJUAN LIU GANG TENG XUEHOU |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20190325 Address after: 265209 Food Industrial Park, Laiyang City, Shandong Province Patentee after: LAIYANG SBOND PHARMACEUTICAL CO.,LTD. Address before: 250216 Longshan Office, Zhangqiu City, Shandong Province, Longhu Road East Patentee before: SHANDONG SIBANGDE PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Zinc gluconate sugar tablet preparation and its preparation method Effective date of registration: 20230704 Granted publication date: 20120328 Pledgee: Postal Savings Bank of China Limited Laiyang sub branch Pledgor: LAIYANG SBOND PHARMACEUTICAL CO.,LTD. Registration number: Y2023980047332 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |