CN1268327C - Brufen arginine pseudoephedrine hydrochloride compound formulation - Google Patents
Brufen arginine pseudoephedrine hydrochloride compound formulation Download PDFInfo
- Publication number
- CN1268327C CN1268327C CN 200410016053 CN200410016053A CN1268327C CN 1268327 C CN1268327 C CN 1268327C CN 200410016053 CN200410016053 CN 200410016053 CN 200410016053 A CN200410016053 A CN 200410016053A CN 1268327 C CN1268327 C CN 1268327C
- Authority
- CN
- China
- Prior art keywords
- parts
- pseudoephedrine
- ibuprofen
- arginine
- ibuprofen arginine
- 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
Links
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 title claims abstract description 108
- -1 Brufen arginine pseudoephedrine hydrochloride compound Chemical class 0.000 title claims description 51
- 229960003447 pseudoephedrine hydrochloride Drugs 0.000 title claims description 17
- 239000000203 mixture Substances 0.000 title claims description 10
- 239000004475 Arginine Substances 0.000 title abstract description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 title abstract description 3
- 238000009472 formulation Methods 0.000 title 1
- 229960003908 pseudoephedrine Drugs 0.000 claims abstract description 91
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims abstract description 56
- GCCOJNYCFNSJII-VWMHFEHESA-N [n'-[(4s)-4-amino-4-carboxybutyl]carbamimidoyl]azanium;2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N.CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 GCCOJNYCFNSJII-VWMHFEHESA-N 0.000 claims abstract description 51
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 42
- 238000002360 preparation method Methods 0.000 claims abstract description 36
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 22
- 239000002775 capsule Substances 0.000 claims description 16
- 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 16
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 15
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 15
- 235000009697 arginine Nutrition 0.000 claims description 13
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 11
- 229920002472 Starch Polymers 0.000 claims description 10
- 239000008107 starch Substances 0.000 claims description 10
- 235000019698 starch Nutrition 0.000 claims description 10
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- 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 8
- 239000008101 lactose Substances 0.000 claims description 8
- 239000006187 pill Substances 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 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 5
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 239000000306 component Substances 0.000 claims description 3
- 239000008358 core component Substances 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 239000000080 wetting agent Substances 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims 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 abstract description 30
- 239000003814 drug Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
- 230000002045 lasting effect Effects 0.000 abstract description 2
- 230000000638 stimulation Effects 0.000 abstract description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000007721 medicinal effect Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 description 9
- 238000001035 drying Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000000202 analgesic effect Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 5
- 230000036760 body temperature Effects 0.000 description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- 208000000112 Myalgia Diseases 0.000 description 3
- 206010028748 Nasal obstruction Diseases 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- CAVQBDOACNULDN-NRCOEFLKSA-N (1s,2s)-2-(methylamino)-1-phenylpropan-1-ol;sulfuric acid Chemical compound OS(O)(=O)=O.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 CAVQBDOACNULDN-NRCOEFLKSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- LJDBEOHBGATIIJ-UHFFFAOYSA-N C(C=1C(C(=O)O)=CC=CC1)(=O)O.C(C)O.C(C)O Chemical compound C(C=1C(C(=O)O)=CC=CC1)(=O)O.C(C)O.C(C)O LJDBEOHBGATIIJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020565 Hyperaemia Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 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
- 239000002671 adjuvant Substances 0.000 description 2
- 210000000544 articulatio talocruralis Anatomy 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000002850 nasal mucosa Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229960004159 pseudoephedrine sulfate Drugs 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 235000019994 cava Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003026 hypopharynx Anatomy 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 208000010753 nasal discharge Diseases 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention provides a compound preparation of ibuprofen arginine pseudoephedrine. The preparation contains ibuprofen arginine and pseudoephedrine or pseudoephedrine salts acceptable to medicine, wherein the mass proportion of the ibuprofen arginine to the pseudoephedrine or pseudoephedrine salts acceptable to medicine is from 1 to 40:1. The water solubility of ibuprofen is improved due to the combination of ibuprofen and arginine. On one hand, in vivo absorption rate is increased, and on the other hand, stimulation to the gastrointestinal tract is reduced. Moreover, the obtained compound preparation takes effect rapidly, and the medicinal effects of the compound preparation are stable and lasting.
Description
(1) technical field
The present invention relates to contain the compound preparation of acceptable salt composite on ibuprofen arginine and pseudoephedrine or its medicine.
(2) background technology
Pseudoephedrine or its pharmaceutically acceptable salt (for example pseudoephedrine hydrochloride, pseudoephedrine sulfate) are taken as the sympathomimetic drug for the treatment of nasal congestion effectively by those skilled in the art.That also known ibuprofen (a kind of NSAID (non-steroidal anti-inflammatory drug)) has is analgesic, antiinflammatory, analgesic activity.So, not only contained ibuprofen but also contained pseudoephedrine or the Orally administered composition of its pharmaceutically acceptable salt is applicable to that treatment shows as symptoms such as the headache, fever, laryngopharynx swelling and pain, joint, the whole body and the limb muscle ache that are caused by flu, allergic rhinitis, nasal obstruction, watery nasal discharge, sneeze.
But the ibuprofen in the said composition is because water-soluble hardly, pharmacokinetic parameters T
Max(reaching the time of maximum plasma concentration) value is 1.5-2h, and the same with other oral NSAID (NSAID (non-steroidal anti-inflammatory drug)), onset is slower relatively, and gastrointestinal tract is had certain stimulation.And the pseudoephedrine onset is very fast relatively, and its pharmaceutically acceptable salt (example hydrochloric acid pseudoephedrine, pseudoephedrine sulfate) is after oral, and general the absorption all peaked in 1 hour.0.5 average blood drug level is 274 ± 33 μ g/ml (are example with oral 60mg once) between～2 hours.How to make each prescription in the drug regimen bring into play its effect simultaneously, as early as possible, becoming such medicine mainly needs the technological difficulties that solve.
(3) summary of the invention
The present invention for a kind of rapid-action, efficacy stability is provided and lastingly and is easily promptly contained the compound preparation that ibuprofen contains pseudoephedrine or its pharmaceutically acceptable salt by what patient received, and this compound preparation is the compound preparation of ibuprofen arginine and pseudoephedrine or its pharmaceutically acceptable salt.
The present invention reaches the technical scheme that goal of the invention adopts to be:
It is 1～40: 1 ibuprofen arginine and pseudoephedrine or its pharmaceutically acceptable salt that a kind of ibuprofen arginine pseudoephedrine compound preparation, described preparation contain mass ratio.Ibuprofen has improved the water solublity of ibuprofen because of arginic combination, and absorption rate increases in the body on the one hand, and also having reduced on the other hand stimulates gastrointestinal.
Further, described preparation is that 1～40: 1 ibuprofen arginine and pseudoephedrine or its pharmaceutically acceptable salt and pharmaceutical excipient or carrier are formed by mass ratio.
The fragrant arginine in described Lip river and pseudoephedrine or its pharmaceutically acceptable salt mass ratio preferred 3～30: 1, more preferably 8～15: 1.
Described ibuprofen arginine pseudoephedrine compound preparation can be made into one of following dosage forms:
1. 2. 3. 4. slow releasing capsule of slow releasing tablet of capsule of tablet.
The quality proportioning of described ibuprofen arginine pseudoephedrine compound tablet is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
37.5 parts of lactose
37.5 parts of starch
15 parts of microcrystalline Cellulose
25 parts of 2% polyvidone aqueous solutions
2.8 parts of Pulvis Talci
0.9 part of magnesium stearate
Described ibuprofen arginine pseudoephedrine compound tablet can prepare as follows:
(1) former, adjuvant are crossed 80 mesh sieves respectively;
(2) get ibuprofen arginine and pseudoephedrine hydrochloride recipe quantity and starch mixing, add lactose, microcrystalline Cellulose mixing again;
(3) add 2% polyvidone aqueous solution and make soft material, drying adds Pulvis Talci, magnesium stearate mix homogeneously, tabletting behind the 16 order granulate.
The content quality proportioning of described ibuprofen arginine pseudoephedrine compound capsule is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
10 parts of low-substituted hydroxypropyl celluloses
5 parts of starch
5 parts of micropowder silica gels
Described ibuprofen arginine pseudoephedrine compound capsule can prepare as follows:
(1) gets ibuprofen arginine and 40 mesh sieves, mix homogeneously are crossed in pseudoephedrine recipe quantity, low-substituted hydroxypropyl cellulose, starch, micropowder silica gel.
(2) step (1) gained granule is encapsulated.
The compound sustained-released tablet of described ibuprofen arginine pseudoephedrine is made up of slow release label, release layer and dyed layer;
Described slow release label quality proportioning is:
240～600 parts of ibuprofen arginines
30 parts of lactose
60 parts of HPMC
20 parts of ethyl celluloses
8.2 parts of magnesium stearate
Described release layer quality proportioning is:
500 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
Described dyed layer is:
45 parts of Opadries (Opadry)
The compound sustained-released tablet of described ibuprofen arginine pseudoephedrine can prepare as follows:
(1) by above-mentioned prescription, the ethanol with 75% is wetting agent, and the slow releasing tablet core component is made granule after according to the recipe quantity mix homogeneously, and the adding magnesium stearate is a lubricant, and tabletting obtains the slow release label;
(2) label is added described release layer component according to recipe quantity in coating pan and carry out coating, make plain sheet;
(3) with above plain sheet further with recipe quantity the Opadry coating, promptly get the compound sustained-released tablet of described ibuprofen arginine pseudoephedrine.
The content of described ibuprofen arginine pseudoephedrine compound sustained release capsules is made up of fast release micropill and slow-release micro-pill;
Described fast release micropill quality proportioning is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
8 parts of 2% polyvidone aqueous solutions
100 parts of ethanol
65 parts of celphere
Described slow-release micro-pill quality proportioning is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
15 parts of 2% polyvidone aqueous solutions
150 parts of ethanol
180 parts of celphere
Described ibuprofen arginine pseudoephedrine compound sustained release capsules can prepare as follows:
(1) according to above-mentioned recipe quantity, celphere is put in the fluid bed, by hot-air celphere is suspended, ibuprofen arginine, pseudoephedrine hydrochloride solution (contain PVP, solvent is 50% ethanol) are sprayed onto drying on the celphere, make required fast release micropill;
(2) celphere is put in the fluid bed, celphere is suspended, ibuprofen arginine and pseudoephedrine hydrochloride solution (contain PVP, solvent is 50% ethanol) are sprayed onto drying on the celphere according to above-mentioned recipe quantity, make slow release ball ball core by hot-air.Reuse ethyl cellulose, phthalic acid diethanol, talcous acetone/isopropanol liquid spray coating, drying, get final product slow-release micro-pill.
(3) slow-release micro-pill and fast release micropill are mixed, the cover capsule can obtain described ibuprofen arginine pseudoephedrine compound sustained release capsules.
The beneficial effect of ibuprofen arginine pseudoephedrine compound preparation of the present invention is mainly reflected in: (1) ibuprofen has improved the water solublity of ibuprofen because of arginic combination, has improved the human absorptivity; (2) rapid-action, the efficacy stability of preparation and lasting.
(4) specific embodiment
Embodiment 1: preparation ibuprofen arginine pseudoephedrine compound tablet
Prescription (per 1000 meters):
Ibuprofen arginine 370g
Pseudoephedrine hydrochloride 30g
Lactose 37.5g
Starch 37.5g
Microcrystalline Cellulose 15g
2% polyvidone aqueous solution 25ml
Pulvis Talci 2.8g
Magnesium stearate 0.9g
Technology:
(1) former, adjuvant are crossed 80 mesh sieves respectively;
(2) get ibuprofen arginine and pseudoephedrine hydrochloride recipe quantity and starch mixing, add lactose, microcrystalline Cellulose mixing again;
(3) add 2% polyvidone aqueous solution and make soft material, 70 ℃ of dryings add Pulvis Talci, magnesium stearate mix homogeneously behind the 16 order granulate, measure granule content, tabletting.
Embodiment 2: preparation ibuprofen arginine pseudoephedrine compound capsule
Prescription (per 1000 meters):
Ibuprofen arginine 570g
Pseudoephedrine hydrochloride 30g
Cellulose ethyl hydroxypropyl ether 10g
Starch 5g
Micropowder silica gel 5g
Technology:
(1) gets ibuprofen arginine and 40 mesh sieves, mix homogeneously are crossed in pseudoephedrine recipe quantity, Cellulose ethyl hydroxypropyl ether, starch, micropowder silica gel.
(2) encapsulated.
Embodiment 3: the compound sustained-released tablet of preparation ibuprofen arginine pseudoephedrine
Prescription (per 1000 meters)
The slow release label:
Ibuprofen arginine 400g
Lactose 30g
HPMC 60g
(hydroxypropyl emthylcellulose)
Ethyl cellulose 20g
Magnesium stearate 8.2g
Release layer:
Ibuprofen arginine 500g
Pseudoephedrine hydrochloride 30g
Dyed layer:
Opadry (Opadry) 45g
Technology:
(1) by above-mentioned prescription, the ethanol with 75% is wetting agent, and the slow releasing tablet core component is made granule after according to the recipe quantity mix homogeneously, and the adding magnesium stearate is a lubricant, and tabletting obtains the slow release label;
(2) label is added described release layer component according to recipe quantity in coating pan and carry out coating, make plain sheet;
(3) with above plain sheet further with recipe quantity the Opadry coating, promptly get the compound sustained-released tablet of described ibuprofen arginine pseudoephedrine.
Embodiment 4: preparation ibuprofen arginine pseudoephedrine compound sustained release capsules
1) preparation of fast release micropill
Prescription (per 1000 meters):
Ibuprofen arginine 500g
Pseudoephedrine hydrochloride 30g
2% polyvidone aqueous solution 8g
Ethanol 100ml
Celphere 65g
Technology:
According to above-mentioned recipe quantity, celphere is put in the fluid bed, by hot-air celphere is suspended, with ibuprofen arginine, pseudoephedrine hydrochloride solution (contain PVP, solvent is 50% ethanol), be sprayed onto drying on the celphere, make described fast release micropill.
2) preparation of slow-release micro-pill
Prescription (per 1000 meters):
Ibuprofen arginine 500g
Pseudoephedrine hydrochloride 30g
2% polyvidone aqueous solution 15g
Ethanol 150ml
Celphere 180g
Technology:
Celphere is put in the fluid bed, celphere is suspended, ibuprofen arginine and pseudoephedrine hydrochloride solution (contain PVP, solvent is 50% ethanol) are sprayed onto drying on the celphere according to above-mentioned recipe quantity, make required slow release ball ball core by hot-air.Reuse ethyl cellulose, phthalic acid diethanol, talcous acetone/isopropanol liquid spray coating, drying, get final product slow-release micro-pill.
3) slow-release micro-pill and No. 0 capsule of fast release micropill mixing capsule can be obtained ibuprofen arginine pseudoephedrine compound sustained release capsules.
Embodiment 5: preparation stability is investigated
Embodiment 1 gained tablet is carried out illumination, hot test and accelerated test, investigate its stability.
1) exposure experiments to light
Get embodiment 1 gained tablet, under light intensity 4000Lx, shine, place sample thief observation mensuration after 0,5,10 day respectively, the results are shown in Table 1.
Table 1. ibuprofen arginine Defed exposure experiments to light result
The result shows that this product every index under illumination condition is basicly stable.
2) hot test
Embodiment 1 gained tablet is placed in 60 ℃ of electrothermostats, places sampling observation and mensuration after 5,10 days respectively, result and comparison in 0 day see Table 2.
Table 2. ibuprofen arginine Defed hot test result
The result shows: this product related substance under 60 ℃ of hot conditionss slightly increases, but all less than 1.0%, all the other indexs are basicly stable.
3) accelerated test
Getting embodiment 1 gained tablet, is 40 ℃ ± 2 ℃ in temperature; Relative humidity is to carry out accelerated test under 75% ± 5% condition, the results are shown in Table 3.
Table 3. ibuprofen arginine Defed accelerated test result
| 000822 | White tablets | 0.16 | 109 | 103.5 | |
| March | 000818 | White tablets | 0.13 | 106 | 101.6 |
| 000821 | White tablets | 0.12 | 102 | 103.0 | |
| 000822 | White tablets | 0.12 | 111 | 102.8 | |
| June | 000818 | White tablets | 0.31 | 105 | 100.8 |
| 000821 | White tablets | 0.29 | 105 | 100.7 | |
| 000822 | White tablets | 0.36 | 101 | 102.8 |
The result shows, this product is quickened to investigate six months, every index and relatively having no significant change in 0 month.Can be obtained by above test, the ibuprofen arginine Defed has good stability.
Embodiment 6: the antiinflammatory test
Get body weight 140～160g rat, male and female half and half, random packet, 8 every group.Negative control group (normal saline 25ml/kg), positive controls (ibuprofen pseudoephedrine 34.5mg/kg, wherein contain ibuprofen 30mg, pseudoephedrine contains 4.5mg, and limited company produces by the prosperous enlightening Pharmaceutical of Hubei encyclopaedia), embodiment is prepared into ibuprofen arginine Defed low dose group (5.4mg/kg), middle dosage group (54mg/kg), high dose group (270mg/kg).By the above-mentioned dosage gastric infusion (ig) of respectively organizing, behind the 1h, the sterile working, injection causes scorching thing (1% carrageenin 0.1ml) under every sufficient plantar aponeurosis in a rat left side.Cause scorching back 1h, 3h measures left and right sides ankle joint girth with special moccasin chi.With the difference of left and right sides ankle joint girth as the swelling degree, contrast between organizing, the poor opposite sex).The results are shown in Table 4.
Table 4. ibuprofen arginine pseudoephedrine on Carrageenan causes scorching antiinflammatory action
| Group | Dosage (mg/kg) | Number of animals (only) | Swelling degree (mm) r ± s | The P value | ||
| Cause scorching back 1h | Cause scorching back 3h | Compare with saline | Compare with the ibuprofen pseudoephedrine | |||
| Normal saline | 8 | 6.00±1.25 | 6.81±0.90 | |||
| The ibuprofen pseudoephedrine | 34.5 | 8 | 2.75±0.65 | 2.72±0.92 | ＜0.01 | |
| The ibuprofen arginine pseudoephedrine | 5.4 | 8 | 3.18±1.16 | 2.50±0.59 | ＜0.01 | ＞0.05 |
| 54 | 8 | 1.50±1.20 | 2.52±0.62 | ＜0.01 | ＞0.05 | |
| 270 | 8 | 1.23±0.82 | 1.20±0.67 | ＜0.01 | ＜0.05 |
By last table result as can be seen: during high dose group, effect obviously is better than the ibuprofen pseudoephedrine to the antiinflammatory action of ibuprofen arginine pseudoephedrine about 1h and in giving.
Embodiment 7: the analgesic test
Get 60 of body weight 17～22g mices, male and female half and half, random packet, 12 every group.If the group situation reaches and respectively organizes gastric infusion dosage with embodiment 6.Ip0.6% acetic acid behind the 30min (0.2ml/ only) causes pain, raises to causing indicator reaction bitterly with mouse writhing (abdominal part caves in, trunk uphold with hind leg) buttocks.Turn round the body number of times behind the self-supporting acetic acid of observed and recorded in the 15min.The results are shown in Table 5.
Table 5. ibuprofen arginine pseudoephedrine is to the analgesic activity of mice
| Group | Dosage (mg/kg) | Number of animals (only) | Swelling degree (g) x ± S | The P value | |
| Compare with saline | Compare with the ibuprofen pseudoephedrine | ||||
| Normal saline | 12 | 20.60±5.23 | |||
| The ibuprofen pseudoephedrine | 34.5 | 12 | 5.76±1.52 | ＜0.05 | |
| The ibuprofen arginine pseudoephedrine | 5.4 | 12 | 6.23±2.30 | ＜0.01 | ＞0.05 |
| 54 | 12 | 5.12±2.19 | ＜0.01 | ＞0.05 | |
| 270 | 12 | 2.85±0.47 | ＜0.01 | ＜0.05 | |
By last table result as can be seen: ibuprofen arginine pseudoephedrine compound tablet is when middle dosage, and its analgesic activity is suitable with the ibuprofen pseudoephedrine, and when giving high dose, analgesic activity obviously is better than the ibuprofen pseudoephedrine.
Embodiment 8: separate heat test
Get 40 of body weight 1.6～2.0kg rabbit, male and female half and half, random packet, 8 every group.Ibuprofen arginine Defed low dose group (3.5mg/kg), middle dosage group (16.8mg/kg), the high dose group (78.5mg/kg) of negative control group (normal saline 1ml/kg), positive controls (ibuprofen pseudoephedrine 17.5mg/kg), embodiment 1 preparation.After measuring the rabbit normal body temperature, injection colibacillus deactivating liquid (about 1012/kg antibacterial, reduced turbidity calculates) pyrogenicity.Take temperature is as the fever index behind 3～4h.Reduce number as separating heating index with each time point body temperature behind the gastric infusion.Compare with the body temperature before the back administration that heats up, the results are shown in Table 6.
Table 6 ibuprofen arginine pseudoephedrine is to the influence of rabbit body temperature
| Group | Dosage (mg/kg) | Give behind the bacterium before the administration elevated temperature ℃ | Different time body temperature reduction value after the administration (℃) x ± S | |||
| 60min | 90min | 120min | 150min | |||
| Normal saline | 1.53±0.13 | 0.11±0.10 | 0.15±0.10 | 0.075±0.10 | 0.35±0.20 | |
| The ibuprofen pseudoephedrine | 17.5 | 1.23±0.07 | 0.13±0.10 | 0.61±0.10 | 0.92±0.10 | 1.03±0.20 |
| The ibuprofen arginine pseudoephedrine | 3.5 | 1.55±0.18 | 0.26±0.10 | 0.47±0.20 | 0.80±0.20 | 0.89±0.20 |
| 16.8 | 1.29±0.08 | 0.72±0.10 | 0.84±0.20 | 0.99±0.10 | 1.09±0.20 | |
| 78.5 | 1.69±0.14 | 0.92±0.10 | 1.08±0.20 | 1.25±0.29 | 1.39±0.10 | |
By last table result as can be seen: in giving ibuprofen arginine pseudoephedrine compound tablet during dosage, its for the body-temp. reducing effect of rabbit obviously faster than the ibuprofen pseudoephedrine.But the body-temp. reducing effect basically identical after two hours.
Embodiment 9: clinical efficacy
Picked at random has 60 of the flu volunteer patients of symptoms such as nasal obstruction, rhinorrhea, sneeze, myalgia, nasal mucosa hyperemia, be divided into two groups, each 30 the ibuprofen arginine pseudoephedrine compound tablet that give ibuprofen pseudoephedrine and embodiment 1 preparation respectively, observe it respectively at 0.5h, 1.5h the curative effect when reaching 5h the results are shown in Table 7.
Yellow alkali of table 7. ibuprofen arginine pseudoephedrine and ibuprofen pseudoephedrine clinical efficacy are relatively
| Group | Symptom | Produce effects (%) | Effective percentage (%) | Total effective rate (%) | ||||||
| 0.5h | 1.5h | 5h | 0.5h | 1.5h | 5h | 0.5h | 1.5h | 5h | ||
| The ibuprofen pseudoephedrine | Nasal obstruction | 5.2 | 12.9 | 35.9 | 10.2 | 15.3 | 61.2 | 15.4 | 28.2 | 97.1 |
| The pseudo-Herba Ephedrae cave of ibuprofen arginine | 33.6 | 36.2 | 36.5 | 60.2 | 60.8 | 62.8 | 93.8 | 97.0 | 99.3 | |
| The ibuprofen pseudoephedrine | Nasal mucus | 5.0 | 7.6 | 30.5 | 9.3 | 15.9 | 68.5 | 14.3 | 23.5 | 99.0 |
| The ibuprofen arginine pseudoephedrine | 32.7 | 33.2 | 33.9 | 62.2 | 65.2 | 65.2 | 94.9 | 98.4 | 99.1 | |
| The ibuprofen pseudoephedrine | Sneeze | 6.2 | 7.1 | 30.8 | 5.6 | 10.3 | 65.8 | 11.8 | 17.4 | 96.6 |
| The ibuprofen arginine pseudoephedrine | 32.6 | 32.9 | 33.4 | 61.3 | 65.2 | 66.2 | 93.9 | 98.1 | 99.6 | |
| The ibuprofen pseudoephedrine | Myalgia | 2.0 | 3.5 | 40.8 | 4.8 | 12.5 | 59.2 | 6.8 | 16.0 | 100.0 |
| The ibuprofen arginine pseudoephedrine | 44.7 | 49.7 | 49.7 | 46.8 | 48.2 | 48.9 | 91.5 | 97.9 | 98.6 | |
| The ibuprofen pseudoephedrine | Nasal mucosa hyperemia | 30.2 | 31.5 | 44.6 | 5.3 | 21.3 | 47.6 | 35.5 | 52.8 | 92.2 |
| The ibuprofen arginine pseudoephedrine | 44.7 | 44.8 | 44.9 | 46.8 | 47.6 | 47.7 | 91.5 | 92.4 | 92.6 | |
By last table result as can be seen, ibuprofen arginine pseudoephedrine compound tablet performance drug action is obviously faster than the ibuprofen pseudoephedrine.
Claims (9)
1. ibuprofen arginine pseudoephedrine compound preparation is characterized in that it is 1～40: 1 ibuprofen arginine and pseudoephedrine hydrochloride that described preparation contains mass ratio.
2. ibuprofen arginine pseudoephedrine compound preparation as claimed in claim 1 is characterized in that described preparation is that 1～40: 1 ibuprofen arginine and pseudoephedrine hydrochloride and pharmaceutical excipient or carrier are formed by mass ratio.
3. ibuprofen arginine pseudoephedrine compound preparation as claimed in claim 2 is characterized in that described ibuprofen arginine and pseudoephedrine hydrochloride mass ratio are 3～30: 1.
4. ibuprofen arginine pseudoephedrine compound preparation as claimed in claim 3 is characterized in that described ibuprofen arginine and pseudoephedrine hydrochloride mass ratio are 8～15: 1.
5. as the described ibuprofen arginine pseudoephedrine of claim 1～4 compound preparation, it is characterized in that described preparation can be made into one of following dosage forms:
1. 2. 3. 4. slow releasing capsule of slow releasing tablet of capsule of tablet.
6. ibuprofen arginine pseudoephedrine compound preparation as claimed in claim 5 is characterized in that the quality proportioning of described tablet is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
37.5 parts of lactose
37.5 parts of starch
15 parts of microcrystalline Cellulose
25 parts of 2% polyvidone aqueous solutions
2.8 parts of Pulvis Talci
0.9 part of magnesium stearate
7. ibuprofen arginine pseudoephedrine compound preparation as claimed in claim 5 is characterized in that described capsular content quality proportioning is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
10 parts of low-substituted hydroxypropyl celluloses
5 parts of starch
5 parts of micropowder silica gels
8. ibuprofen arginine pseudoephedrine compound preparation as claimed in claim 5 is characterized in that described slow releasing tablet is made up of slow release label, release layer and dyed layer;
Described slow release label quality proportioning is:
240～600 parts of ibuprofen arginines
30 parts of lactose
60 parts of HPMC
20 parts of ethyl celluloses
8.2 parts of magnesium stearate
Described release layer quality proportioning is:
500 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
Described dyed layer is 45 parts of Opadries (Opadry)
Described slow releasing tablet prepares as follows:
(1) by above-mentioned prescription, the ethanol with 75% is wetting agent, and the slow releasing tablet core component is made granule after according to the recipe quantity mix homogeneously, and the adding magnesium stearate is a lubricant, and tabletting obtains the slow release label;
(2) label is added described release layer component according to recipe quantity in coating pan and carry out coating, make plain sheet;
(3) with above plain sheet further with recipe quantity the Opadry coating, promptly get the compound sustained-released tablet of described ibuprofen arginine pseudoephedrine.
9. ibuprofen arginine pseudoephedrine compound preparation as claimed in claim 5 is characterized in that the content of described slow releasing capsule is made up of fast release micropill and slow-release micro-pill;
Described fast release micropill quality proportioning is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
8 parts of 2% polyvidone aqueous solutions
100 parts of ethanol
65 parts of celphere;
Described slow release ball core quality proportioning is:
240～600 parts of ibuprofen arginines
30 parts of pseudoephedrine hydrochlorides
15 parts of 2% polyvidone aqueous solutions
150 parts of ethanol
180 parts of celphere.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410016053 CN1268327C (en) | 2004-01-18 | 2004-01-18 | Brufen arginine pseudoephedrine hydrochloride compound formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410016053 CN1268327C (en) | 2004-01-18 | 2004-01-18 | Brufen arginine pseudoephedrine hydrochloride compound formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1557293A CN1557293A (en) | 2004-12-29 |
| CN1268327C true CN1268327C (en) | 2006-08-09 |
Family
ID=34351672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410016053 Expired - Lifetime CN1268327C (en) | 2004-01-18 | 2004-01-18 | Brufen arginine pseudoephedrine hydrochloride compound formulation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1268327C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101756981B (en) * | 2008-12-16 | 2013-04-10 | 北京科信必成医药科技发展有限公司 | Brufen loratadine pseudoephedrine release preparation and preparation method thereof |
| CN102920691A (en) * | 2012-10-23 | 2013-02-13 | 中美天津史克制药有限公司 | Compound sustained-release capsule containing ibuprofen and pseudo ephedrine |
-
2004
- 2004-01-18 CN CN 200410016053 patent/CN1268327C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CN1557293A (en) | 2004-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1142780C (en) | Pharmaceutical compositions | |
| CN100339078C (en) | Solid drug for oral use | |
| CN87105828A (en) | The quick-acting compositionss of sulindac or sodium sulindac and alkali | |
| CN1762357A (en) | Oral medicinal formulation of moxifloxacin and its preparation method | |
| CN101057862A (en) | Medicinal composition for treating senile osteoarthropathy | |
| CN1155369C (en) | Modified release oral pharmaceutical composition contg. 5-ASA and method for treatment of bowel diseases | |
| CN1148188C (en) | Analgesics | |
| CN1296052C (en) | Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate | |
| CN1799543A (en) | Telmisartan dispersible tablet and its preparation method | |
| CN1268327C (en) | Brufen arginine pseudoephedrine hydrochloride compound formulation | |
| CN1265793C (en) | Oral compound levocetirizine pseudoephedrine formulation and its preparation | |
| CN1217721A (en) | Method for treating or preventing interstitial cystitis | |
| CN1915216A (en) | New usage of tandospirone and its derivative, and composition containing tandospirone | |
| CN1166362C (en) | Solution agent of antiallergi medicine contg. levocetirizine | |
| CN1943561A (en) | Oral disintegration tablet of prulifloxacin and its preparing method | |
| CN1273137C (en) | Compound prepn. contg. Brufen arginine codeine | |
| CN1634087A (en) | Sustained release formulation of glucosamine salt, its preparation and usage | |
| CN1194691C (en) | Composition for curing hyperlipemia | |
| CN1283240C (en) | Pharmaceutical use of COX-2 inhibitors in angiogenesis-mediated ocular disorders | |
| CN101028518A (en) | Medicinal composition containing silver ester medicine and ibobulodine | |
| CN1680390A (en) | Halogenated dihydroartemisine, preparation and use thereof | |
| CN1634299A (en) | Application of fenugreek total alkali extract in preparing medicine for ulcerative colitis and preparation method of colon targeted preparation | |
| CN1810242A (en) | Slow-released vincamine capsule and its prepn process | |
| CN101062039A (en) | Medical combination for treating nervous system diseases | |
| CN1720911A (en) | Pharmaceutical composition containing ambroxol and erdosteine or acetylcysteine and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CX01 | Expiry of patent term |
Granted publication date: 20060809 |
|
| CX01 | Expiry of patent term |