CN1206991C - Preparation containing Cetirizine Hydrochloride and hydrochloric pseudoephedrine and its prepn. method - Google Patents
Preparation containing Cetirizine Hydrochloride and hydrochloric pseudoephedrine and its prepn. method Download PDFInfo
- Publication number
- CN1206991C CN1206991C CN 02145079 CN02145079A CN1206991C CN 1206991 C CN1206991 C CN 1206991C CN 02145079 CN02145079 CN 02145079 CN 02145079 A CN02145079 A CN 02145079A CN 1206991 C CN1206991 C CN 1206991C
- Authority
- CN
- China
- Prior art keywords
- preparation
- hydrochloride
- pseudoephedrine
- cetirizine
- cetirizine hydrochloride
- 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.)
- Expired - Lifetime
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- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 title claims abstract description 84
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title claims abstract description 57
- 229960004342 cetirizine hydrochloride Drugs 0.000 title claims abstract description 52
- 229960003908 pseudoephedrine Drugs 0.000 title abstract description 21
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 title abstract description 21
- 238000000034 method Methods 0.000 title abstract description 12
- BALXUFOVQVENIU-KXNXZCPBSA-N pseudoephedrine hydrochloride Chemical compound [H+].[Cl-].CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-KXNXZCPBSA-N 0.000 claims description 63
- 229960003447 pseudoephedrine hydrochloride Drugs 0.000 claims description 62
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 52
- 239000008187 granular material Substances 0.000 claims description 37
- 229920002472 Starch Polymers 0.000 claims description 34
- 239000008107 starch Substances 0.000 claims description 34
- 235000019698 starch Nutrition 0.000 claims description 34
- 239000003795 chemical substances by application Substances 0.000 claims description 32
- 239000003085 diluting agent Substances 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 28
- 235000019359 magnesium stearate Nutrition 0.000 claims description 26
- 239000011230 binding agent Substances 0.000 claims description 21
- 239000000314 lubricant Substances 0.000 claims description 20
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 18
- 229940049654 glyceryl behenate Drugs 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 16
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 16
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 16
- 229960003943 hypromellose Drugs 0.000 claims description 16
- 238000002156 mixing Methods 0.000 claims description 14
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 8
- 229920000881 Modified starch Polymers 0.000 claims description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 8
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 8
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 8
- 239000007779 soft material Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 6
- 239000008101 lactose Substances 0.000 claims description 6
- 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 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims 1
- 238000007873 sieving Methods 0.000 claims 1
- 230000003203 everyday effect Effects 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 2
- 230000000857 drug effect Effects 0.000 abstract description 2
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 24
- 229960001803 cetirizine Drugs 0.000 description 21
- 239000002002 slurry Substances 0.000 description 18
- 238000012360 testing method Methods 0.000 description 15
- 239000002671 adjuvant Substances 0.000 description 12
- 238000013268 sustained release Methods 0.000 description 12
- 239000012730 sustained-release form Substances 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 7
- 238000005286 illumination Methods 0.000 description 7
- 239000002245 particle Substances 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- ZOPQOWMEWBFVAR-PXRPMCEGSA-N 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid;(1s,2s)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZOPQOWMEWBFVAR-PXRPMCEGSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 229940056152 cetirizine / pseudoephedrine Drugs 0.000 description 5
- -1 4-chlorphenyl Chemical group 0.000 description 4
- 206010020565 Hyperaemia Diseases 0.000 description 4
- 206010028735 Nasal congestion Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 4
- 239000000739 antihistaminic agent Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000002850 nasal mucosa Anatomy 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000002932 luster Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- 238000010953 Ames test Methods 0.000 description 2
- 231100000039 Ames test Toxicity 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010019695 Hepatic neoplasm Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 230000001932 seasonal effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- YWGDWLMVCBDOEN-UHFFFAOYSA-N 2,3-dihydroxypropyl docosanoate;octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO YWGDWLMVCBDOEN-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010028748 Nasal obstruction Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000005946 Xerostomia Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229940057344 bufferin Drugs 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- MZNZKBJIWPGRID-UHFFFAOYSA-N diphenylphosphorylmethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)CP(C=1C=CC=CC=1)C1=CC=CC=C1 MZNZKBJIWPGRID-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 229960004842 ephedrine sulfate Drugs 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 231100000025 genetic toxicology Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical class C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 208000019420 lymphoid neoplasm Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001379 nervous effect Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention discloses a preparation which contains cetirizine hydrochloride and hydrochloric pseudoephedrine and a preparation method thereof. The preparation is a double-layer coating core, wherein a core of the preparation contains hydrochloric pseudoephedrine whose quantity reaches the treatment effective dose and a carrier which can be medically accepted, and an outer layer of the preparation contains a preparation which contains cetirizine hydrochloride whose quantity reaches the treatment effective dose and a carrier which can be medically accepted. An inner layer tablet which contains the hydrochloric pseudoephedrine is firstly prepared, and the inner layer tablet is then coated with an outer layer tablet which contains the cetirizine hydrochloride. The present invention solves the problem that cetirizine hydrochloride is quickly released. Simultaneously, the requirement that hydrochloric pseudoephedrine is slowly released is satisfied. The released quantity of the cetirizine hydrochloride can reach more than 70%(90%) in half an hour (an hour), and the hydrochloric pseudoephedrine can be slowly released in 12 hours or 24 hours. The drug effect is stably kept, and therefore, the number of medication times can be reduced. The preparation which contains the cetirizine hydrochloride and the hydrochloric pseudoephedrine and is prepared according to the method is taken for once or twice every day.
Description
Technical field
The present invention relates to a kind of antfhistamine medicine, particularly contain preparation of cetirizine hydrochloride and pseudoephedrine hydrochloride and preparation method thereof.
Background technology
Cetirizine, its chemical name (±)-2-[2-[4-[(4-chlorphenyl) benzyl]-the 1-piperazinyl] ethyoxyl] acetic acid, molecular formula is C
21H
25CIN
2O
3, pseudoephedrine, its chemical name (1S.2S)-2-methylamino-1-phenyl-1-propanol, molecular formula is C
10H
15NO.
Cetirizine, a kind of metabolite of hydroxyzine is novel second filial generation antihistaminic-H
1-receptor antagonist is very little to the maincenter sedation.Be widely used in the property whole year and seasonal indoor and outdoor anaphylactic disease at present clinically, as symptoms such as acute urticaria, allergic dermatitis, eczemas.Be extensive use of the America and Europe at present.And recorded in European Pharmacopoeia and British Pharmacopoeia.The external Cetirizine hydrochloride Tablets of China's import since the nineties.
Pseudoephedrine is a kind of Orally active sympathomimetic nerve class medicine, has and the similar effect of epinephrine.Be mainly used in upper respiratory diseases such as cold, flu, allergic rhinitis, have to alleviate the nasal obstruction that the congested swelling of nasal mucosa causes, be considered to alleviate because a kind of effective medicine of the hyperemia that allergic rhinitis causes.
The oral administered compound slow releasing tablet that is prepared from by cetirizine hydrochloride and pseudoephedrine hydrochloride, wherein cetirizine hydrochloride is a rapid release, pseudoephedrine hydrochloride is a slow release, cetirizine hydrochloride is good antiallergic agent, and the autopath often is accompanied by nasal congestion, pseudoephedrine hydrochloride has the good curing effect to nasal congestion, nasal mucosa hyperemia simultaneously.Both share the allergic symptom that can be widely used in the treatment belt nasal congestion, and indoor and outdoor allergy and nasal congestion for seasonal and the property whole year can play good therapeutic effect.
Contain the compound preparation that anti-histamine activity composition and/or antipyretic-antalgic class and pseudoephedrine hydrochloride make in the market and mainly contain tablet, capsule and syrup.No matter be that the method that tablet or capsules preparation technique adopt mostly is to mix with proper quantity of medicinal auxiliary material containing the antihistaminic of a certain amount of active ingredient and/or the preparation of antipyretic-antalgic class and pseudoephedrine hydrochloride, through wet granulation, be pressed into tablet behind the wet grain drying of gained or irritate into capsule.This preparation method can't solve the rapid onset of cetirizine hydrochloride and the pseudoephedrine hydrochloride slow release effect mainly contains as medicine common on the present domestic market: new contac, Bufferin Cold, paracetamol etc.
Summary of the invention
One of technical issues that need to address of the present invention provide a kind of preparation that contains cetirizine hydrochloride and pseudoephedrine hydrochloride, to overcome the defective that prior art exists.
Two of the technical issues that need to address of the present invention are to disclose the above-mentioned preparation method that contains the preparation of cetirizine hydrochloride and pseudoephedrine hydrochloride.
Technical scheme
The preparation that contains cetirizine hydrochloride and pseudoephedrine hydrochloride of the present invention is that a kind of chip contains the pseudoephedrine hydrochloride for the treatment of effective dose and medically acceptable carrier, outer double-deck clad sheet for the preparation that contains the cetirizine hydrochloride for the treatment of effective dose and medically acceptable carrier.
The weight ratio of cetirizine hydrochloride and pseudoephedrine hydrochloride is:
Pseudoephedrine hydrochloride: cetirizine hydrochloride=120-480: 5-20;
Preferred ratio is:
Pseudoephedrine hydrochloride: cetirizine hydrochloride=120: 5;
The internal layer carrier comprises blocker, lubricant, binding agent;
Outer carrier comprises diluent, disintegrating agent, lubricant, binding agent.
The blocker of being addressed comprises one or more of stearic acid Glyceryl Behenate, hypromellose K100MCR, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30.Because the pseudoephedrine hydrochloride water solublity is better, only a kind of blocker can not make it reach the slow release requirement.Therefore, inner layer piece preferably adopts fat-soluble blocker Glyceryl Behenate, reduces the hydrophilic of pseudoephedrine hydrochloride, adopts hydrophilic blocker HPMCK100MCR simultaneously, and retardance discharges, thereby reaches slow release effect.
Described disintegrating agent comprises crospolyvinylpyrrolidone or cross-linked carboxymethyl cellulose or carboxymethyl starch sodium.
Described diluent comprise microcrystalline Cellulose or/and lactose or/and starch or/and pregelatinized Starch.
The lubricant of being addressed comprises magnesium stearate or Pulvis Talci;
Described binding agent comprises starch or polyvinylpyrrolidone or low viscosity hypromellose.
Formulation preparation method of the present invention comprises the steps:
(1) inner layer piece preparation technology:
Pseudoephedrine hydrochloride is pulverized, crossed 60～80 mesh sieves,, be positioned over 60-75 ℃ of heating 0.5-4 hour, cross 10～40 orders and get granule with blocker Glyceryl Behenate mix homogeneously;
With above granule and blocker hypromellose mix homogeneously, add ethanol or/and wetting agents such as water make evenly moisteningly, sieve, place 60-75 ℃ of oven dry, granulate sieves;
With the recessed punch die tool of the shallow circle of Φ＜10mm tabletting, be prepared into label.Standby.
(2) outer layer preparation technology:
With cetirizine hydrochloride and diluent mixing;
Binding agent is joined in the said mixture, stir and make soft material, cross 10～40 mesh sieves and make wet granular, oven dry in about 60～85 ℃ is behind 10～40 order granulate; Add lubricant again, mix homogeneously obtains dried granule;
, on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip with the shallow concave punch tool, makes preparation of the present invention.
Of the present invention will contain pseudoephedrine hydrochloride, cetirizine hydrochloride preparation and make clad sheet after, in preparation process, solved cetirizine hydrochloride rapid release problem, also reached the pseudoephedrine hydrochloride slow release requirement simultaneously.The invention solves the rapid onset of cetirizine hydrochloride and the difficult point of pseudoephedrine hydrochloride slow release effect.Cetirizine hydrochloride is half (one) hour, and burst size reaches more than 70% (90%), and pseudoephedrine hydrochloride can slowly discharge in 12 hours or 24 hours, kept drug effect reposefully, reduced the medication number of times with this.Take to once or twice every day by the cetirizine hydrochloride of this method preparation and the preparation of pseudoephedrine hydrochloride.
1, accelerated test
This compound recipe cetirizine/pseudoephedrine slow releasing tablet is loaded in the bottle, and placing temperature is to carry out stable accelerated test under 40 ℃, RH75% condition, investigates the situation of change of appearance luster, content, release respectively, and the review time was respectively 0,1,2,3,6 month.The results are shown in Table 1,2.
Table 1 (40 ℃, RH75%)
Time outward appearance color
Content (%, HPLC)
(moon) pool, character cetirizine pseudoephedrine
0 off-white color 100.58 98.26
1 off-white color 99.77 102.81
2 off-white colors 98.99 101.41
3 off-white colors 95.82 100.06
6 - - -
Table 2 release (40 ℃, RH75%)
Release (%)
Time
0.5 hours 2 hours 4 hours 8 hours
(moon)
Cetirizine pseudoephedrine pseudoephedrine pseudoephedrine pseudoephedrine
0 82.51±1.23 24.41±1.15 56.68±2.46 75.61±1.21 93.23±2.11
1 81.54±5.53 21.09±0.95 50.18±1.88 73.51±1.67 94.36±0.79
2 89.78±1.57 22.31±1.82 49.35±2.03 71.37±1.44 92.04±0.78
3 83.36±3.51 20.29±1.34 47.62±5.38 70.22±5.47 90.38±2.48
6 - - - - -
2. hot test (60 ℃)
Compound recipe cetirizine/pseudoephedrine slow releasing tablet is packed in the bottle, and opening is placed on respectively in 60 ℃ of drying baker and placed ten days, investigates the situation of change of its character, content, release.The results are shown in Table 3,4.
60 ℃ of tests of table 3 high temperature
The pseudo-numb content cetirizine content of condition character
Original white 100.58 98.26
5 days white 99.75 99.31
10 days white 99.36 99.48
60 ℃ of tests of table 4 high temperature release
Release (%) n=6
Condition
0.5h cetirizine hydrochloride 0.5h pseudoephedrine hydrochloride 2h 4h 8h
Original 82.51 24.41 56.68 75.61 93.23
10 days 80.27 18.71 46.52 72.62 92.88
Can be found out that by table 3,4 compound recipe cetirizine/pseudoephedrine slow releasing tablet was placed ten days under 60 ℃ of hot conditionss, release slightly slows down; All the other have no significant change, and meet the quality standard requirement.
High wet test (25 ℃, humidity is 75%, 92.5%)
Compound recipe cetirizine/pseudoephedrine slow releasing tablet is packed in the bottle, and opening is placed in the constant humidity exsiccator, and condition is respectively 25 ℃ of RH92.5% and RH75%, places ten days, investigates their character, content, the situation of change of release respectively.The result shows this product under super-humid conditions, and RH92.5% placed two days, and slice, thin piece is fragmentary; The RH75% slice, thin piece is loose.
The high wet test of table 5
The pseudo-numb content cetirizine content of condition character
Original white 100.58 98.26
RH75% (10 days) white 97.58 95.38
RH92.5％(10 -
White ravel the grain-
My god)
Ten days releases of the high wet test of table 6
Release (%) n=6
Condition
0.5h cetirizine hydrochloride 0.5h pseudoephedrine hydrochloride 2h 4h 8h
Original 82.51 24.41 56.68 75.61 93.23
RH75% (10 days) 83.65 25.12 52.46 70.53 87.45
RH92.5% (10 days)-----
Can find out that by table 5,6 easily the moisture absorption is rotten under super-humid conditions for compound cetirizine hydrochloride/pseudoephedrine hydrochloride slow release sheet, must the anti-moisture absorption of packing.But the situation of change of RH75% test appearance luster, content, release is not obvious.
Exposure experiments to light (illumination is 4500LX)
Compound recipe cetirizine/pseudoephedrine slow releasing tablet being packed in the transparent vessel, be placed in the illumination instrument, is to place 0,5,10 day under the condition of 4500Lx in illumination, investigates their appearance luster, content, the situation of change of release.The results are shown in Table 7,8.
Table 7 illumination 4500LX test
Character content (%)
The pseudoephedrine cetirizine
0 day white 100.58 98.26
5 days white 99.29 99.87
10 days white 99.40 99.43
Table 8 illumination 4500LX release
Release (%) n=6
0.5h cetirizine 0.5h pseudoephedrine 2h 4h 8h
0 day 82.51 24.41 56.68 75.61 93.23
5 days 84.65 20.08 48.29 72.11 92.73
10 days 81.13 19.27 46.64 71.33 93.68
Be to place ten days under the condition of 4500Lx in illumination, remove release and slightly slow down (but meeting quality standard) that other indexs do not have the significant change experimental result and show that illumination to this product influence not quite.
Animal experimental data
Cetirizine is a kind of antihistaminic, and main effect is selectivity retardance H
1-receptor.This anti-histamine activity of cetirizine is unequivocally established in all kinds of animal and human's body experiments.In the animal body and experiment in vitro show and take the activity that negligible anti-parasympathetic nervous effect and antiserum source property are arranged behind the cetirizine, xerostomia often appears after taking cetirizine.The body inner recipient shows that in conjunction with experiment cetirizine is only to H
1-receptor has affinity; Radiolabeled cetirizine in the autoradiography research mice body, result's demonstration enters the amount of the cetirizine of brain and can ignore.Rats in vitro experiment display system is taken cetirizine and can obviously do not occupied cerebellum H
1-receptor.
Pseudoephedrine hydrochloride is the sympatheticomimetic amine substance of a kind of Orally active, can alleviate abnormal rhinitis and cause nasal mucosa hyperemia, and performance alleviates the effect of nasal mucosa hyperemia, and the border effect of its generation is similar to ephedrine, and main effects is similar to amphetamine.
Cetirizine: in the research in 2 years of rat, when dosage at the dosage of every day regulation during to 20mg/kg (approximately the adult is with 15 times of mg/m2 calculating recommended dose every day), cetirizine does not have carcinogenecity.In the research in 2 years of mice, and when dosage during at 4mg/kg every day (approximately the adult calculates 2 times of recommended dose every day with mg/m2), the incidence rate that male mice is suffered from liver neoplasm does not increase, when dosage during at 16mg/kg every day (approximately the adult calculates 6 times of recommended dose every day with mg/m2), the incidence rate that male mice is suffered from optimum liver neoplasm increases.This slow releasing tablet is data clinically not also.
Pseudoephedrine: according to the prediction of national toxicity program, rat and mice 2 years studies show that, ephedrine sulfate (a kind of similar to pseudoephedrine aspect pharmacology, the medicine that structure is relevant with pseudoephedrine) is when dosage to 10 and 27mg/kg (about be grown up with mg/m of dosage in regulation every day
2Calculate recommended dose every day 1/3 and 1/2) time, do not have a carcinogenecity.
Cetirizine is not seen mutagenicity in (the inspection carcinogen) Ames test and mouse lymph lymphoma test, micronucleus test in test of human lymphoid's tumor and the rodent body is not had cavity.Equally, cetirizine and pseudoephedrine share with 1: 24 ratio, also do not have mutability and cavity in these trials.Yet, Ames test and the not strict test standard that depends on of mouse lymph lymphoma test.
In the research of rat genotoxicity, when cetirizine and pseudoephedrine Combined with Oral dosage reach 6/154mg/kg (approximately the adult is with 5 times of mg/m2 calculating recommended dose every day), reproductive performance there is not influence.
Using method of the present invention is: pseudoephedrine hydrochloride: cetirizine hydrochloride=120mg: 5mg is that 12 hours slow releasing tablet recommendation consumptions are one day twice, each a slice, ante cibum or one after each meal; Pseudoephedrine hydrochloride: cetirizine hydrochloride=240mg: 10mg is that 24 hours slow releasing tablet recommendation consumptions are once-a-day, each a slice, ante cibum or one after each meal.
The specific embodiment
Embodiment 1
1. pseudoephedrine hydrochloride internal layer label preparation (1000):
Former, the effect of adjuvant weight
Pseudoephedrine hydrochloride 120g active component
Glyceryl Behenate 70g sustained-release agent
Hypromellose K100MCR 30g sustained-release agent
Magnesium stearate 5g lubricant
Gross weight 225g
With the pseudoephedrine hydrochloride crushing screening, with Glyceryl Behenate, hypromellose mix homogeneously, add 75% ethanol and make even moistening, cross 18 orders or 24 mesh sieves, place 60-75 ℃ of oven dry, add magnesium stearate, mixing with 16 orders or the 20 mesh sieves granulate that sieves, with diameter (φ) is the shallow concave punch tool tabletting of 9mm, is prepared into label.Standby.
2. outer bag slug particle preparation (1000):
Former, adjuvant weight (g) effect
Cetirizine hydrochloride 5 principal agents
Microcrystalline Cellulose PH101 120 diluent
Lactose 100 diluent
Pregelatinized Starch 80 diluent
Crospolyvinylpyrrolidone XL 20 disintegrating agents
Starch slurry (6%) 10 binding agent
Magnesium stearate 5 lubricants
Total amount 340
Adopt class equivalent incremental method, with cetirizine hydrochloride and diluent mixing progressively.Take by weighing a certain amount of starch, be mixed with concentration and be 6% starch slurry.Make binding agent with starch slurry, join in right amount in the said mixture, stir and make soft material, cross 16 orders or 24 mesh sieves and make wet granular, oven dry in about 80 ℃ is behind 18 orders or 24 order granulate; Add magnesium stearate again, mix homogeneously, obtain dried granule after, adopt diameter (φ) be the shallow concave punch tool of 12.5mm on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip, make this product.This product is 12 hours slow releasing tablet, and 1 hour cetirizine hydrochloride of release reaches more than 95%, and 1 hour release of pseudoephedrine hydrochloride is 20-35%, and 4 hours is 50-80%, and 8 hours greater than about 85%.
Embodiment 2
1. pseudoephedrine hydrochloride internal layer label preparation (1000):
Former, the effect of adjuvant weight
Pseudoephedrine hydrochloride 90g active component
Glyceryl Behenate 40g sustained-release agent
Hypromellose K100MCR 50g sustained-release agent
Magnesium stearate 5g lubricant
Gross weight 185g
The pseudoephedrine hydrochloride crushing screening was mixed 60 mesh sieves with Glyceryl Behenate, put 70 ± 5 ℃ of bakings 2 hours, behind 20 mesh sieves, mix excessively with hypromellose, add 75% ethanol and make even moistening, cross 18 orders or 24 mesh sieves, place 70 ± 5 ℃ of oven dry, with 18 orders or the 20 mesh sieves granulate that sieves, add magnesium stearate, mixing is the shallow concave punch tool tabletting of 8mm with diameter (φ), is prepared into label.Standby.
2. outer bag slug particle preparation (1000):
Former, adjuvant weight (g) effect
Cetirizine hydrochloride 5 principal agents
Pseudoephedrine hydrochloride 30 principal agents
Microcrystalline Cellulose PH101 120 diluent
Lactose 100 diluent
Pregelatinized Starch 80 diluent
Crospolyvinylpyrrolidone XL 20 disintegrating agents
Starch slurry (6%) 10 binding agent
Magnesium stearate 5 lubricants
Total amount 370
Adopt class equivalent incremental method, with two kinds of principal agents and diluent mixing progressively.Take by weighing a certain amount of starch, be mixed with concentration and be 6% starch slurry.Make binding agent with starch slurry, join in right amount in the said mixture, stir and make soft material, cross 16 orders or 24 mesh sieves and make wet granular, oven dry in about 80 ℃ is behind 18 orders or 24 order granulate; Add magnesium stearate again, mix homogeneously, obtain dried granule after, adopt diameter (φ) be the shallow concave punch tool of 12.5mm on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip, make this product.This product is 12 hours slow releasing tablet, and 1 hour cetirizine hydrochloride of release reaches more than 95%, and 1 hour release of pseudoephedrine hydrochloride is 20-35%, and 4 hours is 50-80%, and 8 hours greater than about 85%.
Embodiment 3
1. pseudoephedrine hydrochloride internal layer label preparation (1000):
Former, the effect of adjuvant weight
Pseudoephedrine hydrochloride 240g active component
Glyceryl Behenate 50g sustained-release agent
Hypromellose K100MCR 50g sustained-release agent
Magnesium stearate 5g lubricant
Gross weight 345g
With the pseudoephedrine hydrochloride crushing screening, with Glyceryl Behenate, hypromellose mix homogeneously, add 75% ethanol and make even moistening, cross 18 orders or 24 mesh sieves, place 60-75 ℃ of oven dry, add magnesium stearate, mixing with 16 orders or the 20 mesh sieves granulate that sieves, with diameter (φ) is the shallow concave punch tool tabletting of 10mm, is prepared into label.Standby.
2. outer bag slug particle preparation (1000):
Former, adjuvant weight (g) effect
Cetirizine hydrochloride 10 principal agents
Microcrystalline Cellulose PH101 150 diluent
Starch 80 diluent
Pregelatinized Starch 80 diluent
Crospolyvinylpyrrolidone XL 25 disintegrating agents
Starch slurry (6%) 15 binding agent
Magnesium stearate 5 lubricants
Total amount 365
Adopt class equivalent incremental method, with cetirizine hydrochloride and diluent mixing progressively.Take by weighing a certain amount of starch, be mixed with concentration and be 6% starch slurry.Make binding agent with starch slurry, join in right amount in the said mixture, stir and make soft material, cross 16 orders or 24 mesh sieves and make wet granular, oven dry in about 80 ℃ is behind 18 orders or 24 order granulate; Add magnesium stearate again, mix homogeneously, obtain dried granule after, adopt diameter (φ) be the shallow concave punch tool of 12.5mm on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip, make this product.This product is a slow releasing tablet, and 1 hour cetirizine hydrochloride of release reaches more than 95%, and 1 hour release of pseudoephedrine hydrochloride is 15-35%, and 4 hours is 30-50%, and 12 hours is 50-80%, and 24 hours greater than about 85%.
Embodiment 4
1. pseudoephedrine hydrochloride internal layer label preparation (1000):
Former, the effect of adjuvant weight
Pseudoephedrine hydrochloride 240g active component
Glyceryl Behenate 55g sustained-release agent
Sodium carboxymethyl cellulose 50g sustained-release agent
Magnesium stearate 5g lubricant
Gross weight 350g
With the pseudoephedrine hydrochloride crushing screening, with Glyceryl Behenate, hypromellose mix homogeneously, add 75% ethanol and make even moistening, cross 18 orders or 24 mesh sieves, place 60-75 ℃ of oven dry, add magnesium stearate, mixing with 16 orders or the 20 mesh sieves granulate that sieves, with diameter (φ) is the shallow concave punch tool tabletting of 10mm, is prepared into label.Standby.
2. outer bag slug particle preparation (1000):
Former, adjuvant weight (g) effect
Cetirizine hydrochloride 10 principal agents
Microcrystalline Cellulose PH101 150 diluent
Lactose 80 diluent
Starch 50 diluent
Pregelatinized Starch 80 diluent
Crospolyvinylpyrrolidone XL 20 disintegrating agents
Starch slurry (6%) 10 binding agent
Magnesium stearate 5 lubricants
Total amount 405
Adopt class equivalent incremental method, with cetirizine hydrochloride and diluent mixing progressively.Take by weighing a certain amount of starch, be mixed with concentration and be 6% starch slurry.Make binding agent with starch slurry, join in right amount in the said mixture, stir and make soft material, cross 16 orders or 24 mesh sieves and make wet granular, oven dry in about 80 ℃ is behind 18 orders or 24 order granulate; Add magnesium stearate again, mix homogeneously, obtain dried granule after, adopt diameter (φ) be the shallow concave punch tool of 12mm on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip, make this product.1 hour release of pseudoephedrine hydrochloride is 15-35%, and 4 hours is 30-50%, and 12 hours is 50-80%, and 24 hours greater than about 85%.
Embodiment 5
1. pseudoephedrine hydrochloride internal layer label preparation (1000):
Former, the effect of adjuvant weight
Pseudoephedrine hydrochloride 180g active component
Glyceryl Behenate 50g sustained-release agent
Hypromellose K100MCR 50g sustained-release agent
Magnesium stearate 5g lubricant
Gross weight 285g
With the pseudoephedrine hydrochloride crushing screening, with Glyceryl Behenate, hypromellose mix homogeneously, add 75% ethanol and make even moistening, cross 18 orders or 24 mesh sieves, place 60-75 ℃ of oven dry, add magnesium stearate, mixing with 16 orders or the 20 mesh sieves granulate that sieves, with diameter (φ) is the shallow concave punch tool tabletting of 10mm, is prepared into label.Standby.
2. outer bag slug particle preparation (1000):
Former, adjuvant weight (g) effect
Cetirizine hydrochloride 10 principal agents
Pseudoephedrine hydrochloride 60 principal agents
Microcrystalline Cellulose PH101 150 diluent
Starch 80 diluent
Pregelatinized Starch 80 diluent
Crospolyvinylpyrrolidone XL 25 disintegrating agents
Starch slurry (6%) 15 binding agent
Magnesium stearate 5 lubricants
Total amount 425
Adopt class equivalent incremental method, with two kinds of principal agents and diluent mixing progressively.Take by weighing a certain amount of starch, be mixed with concentration and be 6% starch slurry.Make binding agent with starch slurry, join in right amount in the said mixture, stir and make soft material, cross 16 orders or 24 mesh sieves and make wet granular, oven dry in about 80 ℃ is behind 18 orders or 24 order granulate; Add magnesium stearate again, mix homogeneously, obtain dried granule after, adopt diameter (φ) be the shallow concave punch tool of 12.5mm on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip, make this product.This product is a slow releasing tablet, and 1 hour cetirizine hydrochloride of release reaches more than 95%, and 1 hour release of pseudoephedrine hydrochloride is 15-35%, and 4 hours is 30-50%, and 12 hours is 50-80%, and 24 hours greater than about 85%.
Embodiment 6
1. pseudoephedrine hydrochloride internal layer label preparation (1000):
Former, the effect of adjuvant weight
Pseudoephedrine hydrochloride 240g active component
Glyceryl Behenate 50g sustained-release agent
Sodium carboxymethyl cellulose 40g sustained-release agent
Polyethylene pyrrole Lip river alkane ketone K30 15 binding agents
Magnesium stearate 5g lubricant
Gross weight 350g
With the pseudoephedrine hydrochloride crushing screening, with Glyceryl Behenate, hypromellose mix homogeneously, add 75% ethanol and make even moistening, cross 18 orders or 24 mesh sieves, place 60-75 ℃ of oven dry, add magnesium stearate, mixing with 16 orders or the 20 mesh sieves granulate that sieves, with diameter (φ) is the shallow concave punch tool tabletting of 10mm, is prepared into label.Standby.
2. outer bag slug particle preparation (1000):
Former, adjuvant weight (g) effect
Cetirizine hydrochloride 10 principal agents
Microcrystalline Cellulose PH101 150 diluent
Lactose 80 diluent
Starch 50 diluent
Pregelatinized Starch 80 diluent
Crospolyvinylpyrrolidone XL 20 disintegrating agents
Starch slurry (6%) 10 binding agent
Magnesium stearate 5 lubricants
Total amount 405
Adopt class equivalent incremental method, with cetirizine hydrochloride and diluent mixing progressively.Take by weighing a certain amount of starch, be mixed with concentration and be 6% starch slurry.Make binding agent with starch slurry, join in right amount in the said mixture, stir and make soft material, cross 16 orders or 24 mesh sieves and make wet granular, oven dry in about 80 ℃ is behind 18 orders or 24 order granulate; Add magnesium stearate again, mix homogeneously, obtain dried granule after, adopt diameter (φ) be the shallow concave punch tool of 12mm on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip, make this product.1 hour release of pseudoephedrine hydrochloride is 15-35%, and 4 hours is 30-50%, and 12 hours is 50-80%, and 24 hours greater than about 85%.
Claims (11)
1. the preparation that contains cetirizine hydrochloride and pseudoephedrine hydrochloride is characterized in that containing the pseudoephedrine hydrochloride for the treatment of effective dose and medically acceptable carrier, outer double-deck clad sheet for the preparation that contains the cetirizine hydrochloride for the treatment of effective dose and medically acceptable carrier for a kind of chip.
2. preparation according to claim 1 is characterized in that the weight ratio of cetirizine hydrochloride and pseudoephedrine hydrochloride is:
Pseudoephedrine hydrochloride: cetirizine hydrochloride=120-480: 5-20.
3. preparation according to claim 2 is characterized in that ratio is:
Pseudoephedrine hydrochloride: cetirizine hydrochloride=120: 5.
4. preparation according to claim 1 is characterized in that the internal layer carrier comprises blocker, lubricant, binding agent; Outer carrier comprises diluent, disintegrating agent, lubricant, binding agent.
5. preparation according to claim 4 is characterized in that the blocker of being addressed comprises one or more of Glyceryl Behenate, hypromellose K100MCR, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30.
6. preparation according to claim 5 is characterized in that the blocker of being addressed of being addressed is fat-soluble blocker Glyceryl Behenate and HPMCK100.
7. preparation according to claim 4 is characterized in that disintegrating agent comprises crospolyvinylpyrrolidone, cross-linked carboxymethyl cellulose or carboxymethyl starch sodium.
8. preparation according to claim 4, it is characterized in that the diluent of being addressed comprises microcrystalline Cellulose or/and lactose or/and starch or/and pregelatinized Starch.
9. preparation according to claim 4 is characterized in that the lubricant of being addressed comprises magnesium stearate or Pulvis Talci.
10. preparation according to claim 4 is characterized in that the binding agent of being addressed comprises starch or polyvinylpyrrolidone or low viscosity hypromellose.
11., it is characterized in that comprising the steps: according to the preparation method of each described preparation of claim 1～10
(1) inner layer piece preparation:
Pseudoephedrine hydrochloride is pulverized, is sieved,, be positioned over 60-75 ℃ of heating 0.5～4 hour with blocker Glyceryl Behenate mix homogeneously, sieve granule; Or the pulverizing that is mixed of pseudoephedrine hydrochloride and blocker Glyceryl Behenate, sieve, put 60-85 ℃ of heating 0.5～4 hour, sieve granule;
With above granule and blocker hypromellose mix homogeneously, add ethanol or/and water is moistening, sieve, place 60-75 ℃ of oven dry, granulate sieves;
With the recessed punch die tool of the shallow circle of Ф＜10mm tabletting, be prepared into label;
(2) outer layer preparation:
With cetirizine hydrochloride and diluent mixing;
Binding agent is joined in the said mixture, stir and make soft material, sieving makes wet granular, and oven dry behind the granulate that sieves, adds lubricant again, and mix homogeneously obtains dried granule;
, on the clad sheet tablet machine, above-mentioned dried granule is pressed in outside the chip with the shallow concave punch tool, makes preparation of the present invention.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02145079 CN1206991C (en) | 2002-11-06 | 2002-11-06 | Preparation containing Cetirizine Hydrochloride and hydrochloric pseudoephedrine and its prepn. method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02145079 CN1206991C (en) | 2002-11-06 | 2002-11-06 | Preparation containing Cetirizine Hydrochloride and hydrochloric pseudoephedrine and its prepn. method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1498617A CN1498617A (en) | 2004-05-26 |
| CN1206991C true CN1206991C (en) | 2005-06-22 |
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| CN 02145079 Expired - Lifetime CN1206991C (en) | 2002-11-06 | 2002-11-06 | Preparation containing Cetirizine Hydrochloride and hydrochloric pseudoephedrine and its prepn. method |
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| CN101073563B (en) * | 2007-02-07 | 2010-10-06 | 西安利君制药有限责任公司 | Chiral composition containing dextrothyroxine buprofenli and levomethadyl cysteliqin and its double slow-releasing tablet |
| CN101708178B (en) * | 2009-12-14 | 2012-02-29 | 扬子江药业集团有限公司 | Compound sustained-release tablet of cetirizine and pseudoephedrine and preparation method thereof |
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