CN102144962B - Powdered osletamirvir phosphate medicinal composition - Google Patents
Powdered osletamirvir phosphate medicinal composition Download PDFInfo
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- CN102144962B CN102144962B CN2011100367962A CN201110036796A CN102144962B CN 102144962 B CN102144962 B CN 102144962B CN 2011100367962 A CN2011100367962 A CN 2011100367962A CN 201110036796 A CN201110036796 A CN 201110036796A CN 102144962 B CN102144962 B CN 102144962B
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- oseltamivir phosphate
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- composite medicament
- sodium
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- 239000000203 mixture Substances 0.000 title abstract description 43
- 229910019142 PO4 Inorganic materials 0.000 title abstract description 4
- 239000010452 phosphate Substances 0.000 title abstract description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 61
- 239000007787 solid Substances 0.000 claims abstract description 48
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000000661 sodium alginate Substances 0.000 claims abstract description 40
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 40
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 40
- 239000007788 liquid Substances 0.000 claims abstract description 18
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 5
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 claims description 87
- 229960002194 oseltamivir phosphate Drugs 0.000 claims description 74
- 239000002131 composite material Substances 0.000 claims description 43
- 238000002360 preparation method Methods 0.000 claims description 25
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 17
- 239000000600 sorbitol Substances 0.000 claims description 17
- 239000001509 sodium citrate Substances 0.000 claims description 14
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical group O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 14
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 13
- 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 13
- 229930195725 Mannitol Natural products 0.000 claims description 13
- 239000008101 lactose Substances 0.000 claims description 13
- 239000000594 mannitol Substances 0.000 claims description 13
- 235000010355 mannitol Nutrition 0.000 claims description 13
- 229920001285 xanthan gum Polymers 0.000 claims description 13
- 239000000230 xanthan gum Substances 0.000 claims description 12
- 235000010493 xanthan gum Nutrition 0.000 claims description 12
- 229940082509 xanthan gum Drugs 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 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 description 5
- 229930006000 Sucrose Natural products 0.000 claims description 5
- 239000005720 sucrose Substances 0.000 claims description 5
- 239000000945 filler Substances 0.000 claims description 4
- 239000002562 thickening agent Substances 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical group OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 230000002421 anti-septic effect Effects 0.000 claims description 2
- -1 antiseptic Substances 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 239000001508 potassium citrate Substances 0.000 claims description 2
- 229960002635 potassium citrate Drugs 0.000 claims description 2
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 2
- 235000011082 potassium citrates Nutrition 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 229960001790 sodium citrate Drugs 0.000 claims description 2
- 235000011083 sodium citrates Nutrition 0.000 claims description 2
- 239000001540 sodium lactate Substances 0.000 claims description 2
- 229940005581 sodium lactate Drugs 0.000 claims description 2
- 235000011088 sodium lactate Nutrition 0.000 claims description 2
- 229940074404 sodium succinate Drugs 0.000 claims description 2
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 claims description 2
- 239000000725 suspension Substances 0.000 abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 24
- 239000002671 adjuvant Substances 0.000 description 16
- 229920003023 plastic Polymers 0.000 description 14
- 239000004033 plastic Substances 0.000 description 14
- 229960003752 oseltamivir Drugs 0.000 description 13
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 12
- 238000005303 weighing Methods 0.000 description 11
- 206010022000 influenza Diseases 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 8
- 229940085605 saccharin sodium Drugs 0.000 description 8
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 8
- 235000010234 sodium benzoate Nutrition 0.000 description 8
- 239000004299 sodium benzoate Substances 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 102000005348 Neuraminidase Human genes 0.000 description 2
- 108010006232 Neuraminidase Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 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 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 229940123424 Neuraminidase inhibitor Drugs 0.000 description 1
- BVPQTPZRBARAOA-UHFFFAOYSA-M [K+].OC.CC#N.OP(O)([O-])=O Chemical compound [K+].OC.CC#N.OP(O)([O-])=O BVPQTPZRBARAOA-UHFFFAOYSA-M 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940006355 oseltamivir 75 mg Drugs 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000002911 sialidase inhibitor Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a powdered osletamirvir phosphate medicinal composition. The composition comprises osletamirvir phosphate with effective quantity for treatment or prevention, sodium alginate and optional one or more pharmaceutically acceptable excipients. The invention also provides an application of the solid medicinal composition in preparing an oral liquid medicament. The invention further provides a liquid medicinal composition, which comprises the solid medicinal composition and a water-bearing medium. The solid medicinal composition has a stable and excellent effect after being prepared into a suspension with water.
Description
Technical field
The present invention relates to the novel medicament compositions of oseltamivir phosphate.
Background technology
Neuraminidase (NA) inhibitor is one type of anti-influenza virus medicament developing in recent years; Oseltamivir phosphate is as a kind of neuraminidase inhibitor of up-to-date development; Have to A, Type B influenza virus all effectively, be difficult for drug resistance and advantages such as patient tolerability is good, safety height, be used for prevention and treatment influenza clinically.
Oseltamivir (Oseltamivr uses with its phosphate) is the medicine for treatment of World Health Organization (WHO) and China's Ministry of Public Health prevention and control flu outbreak, also is the national strategy deposit medicine of China and countries in the world prevention and control flu outbreak.
At present, in China commercially available oseltamivir phosphate dosage form being arranged is capsule, and its UD is 98.5mg/ grain (wherein containing Oseltamivir 75mg), according to body weight-dose form that the child more than 1 years old is recommended, takes oseltamivir phosphate dosage and sees the following form:
It is thus clear that capsule is too big because of dosage, be difficult for accurate administration for child patient especially underage child patient, can't guarantee the safety of administration; On the other hand, because old people, child and influenza patient with severe symptoms swallow inconvenience or dysphagia, capsule formulation is for these specific crowds and be not suitable for.Therefore, need exploitation to be fit to the oseltamivir phosphate novel form that old people, child and influenza patient with severe symptoms take.
Summary of the invention
The object of the present invention is to provide a kind of oseltamivir phosphate pharmaceutical composition of novelty, expect its can face with before be mixed with liquid preparation, it is favourable that liquid preparation is taken medicine for old people, child and influenza patient with severe symptoms.It is extremely beneficial for oseltamivir phosphate is provided in the stability of facing when before being mixed with liquid preparation that the inventor finds to use special adjuvant.The present invention is based on this discovery and be accomplished.
Therefore, the invention provides following various aspects:
[1] a kind of solid composite medicament wherein comprises oseltamivir phosphate, the sodium alginate of treatment or prevention effective dose and the acceptable excipient of choosing wantonly of one or more pharmacy.
[2] according to the solid composite medicament of project 1, wherein the weight ratio of sodium alginate and oseltamivir phosphate is (0.01～100): 1, preferred (0.1～10): 1, preferred (0.1～5): 1.
[3] according to the solid composite medicament of project 1, the acceptable excipient of wherein said pharmacy is selected from filler, buffer agent, thickening agent, antiseptic, flavoring agent, sweeting agent.
[4] according to the solid composite medicament of project 3, wherein said filler is selected from sorbitol, mannitol, lactose, sucrose.
[5] according to the solid composite medicament of project 3, wherein said buffer agent is selected from sodium citrate, potassium citrate, sodium lactate, sodium succinate.
[6] according to the solid composite medicament of project 3, wherein said thickening agent is selected from xanthan gum (xanthan gam), sodium carboxymethyl cellulose.
[7] according to each solid composite medicament of project 1-6; Wherein comprise sorbitol and/or mannitol and/or the lactose of sodium alginate, 0.01～1000 weight portion (preferred 0.1～100 weight portion) of oseltamivir phosphate, 0.01～100 weight portion (preferred 0.1～10 weight portion) of 1 weight portion, the sodium citrate of 0.01～100 weight portion (preferred 0.01～10 weight portion), the xanthan gum of 0.01～100 weight portion (preferred 0.01～10 weight portion), and the saccharin sodium of the sodium benzoate of optional 0.001～10 weight portion (preferred 0.01～1 weight portion), optional 0.001～10 weight portion (preferred 0.01～1 weight portion).
[8] purposes of each solid composite medicament of project 1-7 in preparation liquid medicine for oral use.
[9] a kind of composition of liquid medicine; Each solid composite medicament or the composition that wherein comprised (this moment, each composition added up to 1 weight portion) of project 1-7 that wherein comprises 1 weight portion; And the water-bearing media of 2-100 weight portion (preferred 2-50 weight portion, preferred 5-20 weight portion).
[10] composition of liquid medicine of project 9, wherein said water-bearing media is selected from: water, syrup, glucose solution, sodium chloride solution, fruit drink, Ringer's mixture.
The present invention also provides the disease that a kind of treatment or flu-prevention virus caused or the method for illness, the perhaps method of treatment or flu-prevention, and said method comprises the following steps: a) to make said solid composite medicament form suspension with water-bearing media; And b) as required to the aqueous solution of patient's orally give gained.
In one aspect, the present invention also provides solid composite medicament or the composition of liquid medicine that has like the prescription of being put down in writing in this paper embodiment or the preparation example.And the used unit of weight of each composition can change weight portion in these embodiment or the preparation example.
Solid composite medicament of the present invention also can be described as granule or dry suspension, and this is known at pharmaceutical field.Oseltamivir phosphate granula of the present invention can be deployed into solution facing with preceding water or other water-bearing media; Thereby being particularly suitable for the inconvenient patient of child and swallowable capsule takes; Dosage can be selected to use according to patient's age and body weight easily; And its preparation technology is simple and easy to do, and is with low cost.
In one embodiment, solid composite medicament of the present invention comprises:
Oseltamivir phosphate 1 weight portion,
Sodium alginate 0.1～10 weight portion,
Sorbitol and/or mannitol and/or lactose 0.1～100 weight portion.
In one embodiment, solid composite medicament of the present invention comprises:
Oseltamivir phosphate 1 weight portion,
Sodium alginate 0.1～10 weight portion,
Sorbitol and/or mannitol and/or lactose 0.1～100 weight portion,
Sodium citrate 0.01～10 weight portion.
In one embodiment, solid composite medicament of the present invention comprises:
Oseltamivir phosphate 1 weight portion,
Sodium alginate 0.1～10 weight portion,
Sorbitol and/or mannitol and/or lactose 0.1～100 weight portion,
Sodium citrate 0.01～10 weight portion,
Xanthan gum 0.01～10 weight portion.
In one embodiment, solid composite medicament of the present invention comprises:
Oseltamivir phosphate 1 weight portion,
Sodium alginate 0.1～10 weight portion,
Sorbitol and/or mannitol and/or lactose 0.1～100 weight portion,
Sodium citrate 0.01～10 weight portion,
Xanthan gum 0.01～10 weight portion,
Sodium benzoate 0.01～1 weight portion,
Saccharin sodium 0.01～1 weight portion.
In one embodiment, solid composite medicament of the present invention comprises:
Oseltamivir phosphate 1 weight portion,
Sodium alginate 0.1～5 weight portion,
Sorbitol and/or mannitol and/or lactose 5～50 weight portions,
Sodium citrate 0.01～2 weight portion,
Xanthan gum 0.01～2 weight portion,
Sodium benzoate 0.01～1 weight portion,
Saccharin sodium 0.01～0.1 weight portion.
Those skilled in the art know that; Solid composite medicament of the present invention; Can be used as a kind of dry suspension and offer the patient, promptly the solid composite medicament of the present invention as dry suspension is to be solid state in preparation, storage, transportation, before the patient faces usefulness; To wherein adding entry or other suitable water-bearing media; Process suspension, just can directly take for the patient, this moment, the liquid preparation as suspension was particularly advantageous for particular patient (for example children's, old people or patient with severe symptoms) aspect the divided dose.But, it will be apparent to those skilled in the art that this suspension can be used as the multiple dose medicament and possibly need to preserve a couple of days, thus its to have acceptable clinically stability be necessary, for example placed at normal temperatures 10 days, should keep gratifying stability.
According to the present invention, said sodium alginate is to meet standard that for example American Pharmacopeia, British Pharmacopoeia or the European Pharmacopoeia of current edition put down in writing.These products are to obtain easily on the market.
According to the present invention, phrase " sorbitol and/or mannitol and/or lactose " be meant contain in the pharmaceutical composition of the present invention among sorbitol, mannitol and the lactose three any one, two kinds or three kinds.
The method for preparing of solid composite medicament of the present invention is well known to a person skilled in the art, each composition is simply mixed, and for example mixes through the equivalent incremental method; Fully after the mix homogeneously, in pack into vial or the plastic bottle, seal.In addition; Also is very easy by solid composite medicament of the present invention facing with preceding obtaining liq pharmaceutical composition; For example in above-mentioned solid composite medicament in vial or plastic bottle, quantitatively add entry or other water-bearing media, fully be mixed, take according to routine dose and get final product.Thus, solid composite medicament of the present invention and composition of liquid medicine can be used as the multiple dose use.The present invention finds that solid composite medicament water of the present invention is made into after the suspension, and it has good stable property, particularly can place at normal temperatures at least 10 days.
The specific embodiment
Embodiment 1: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight |
| Oseltamivir phosphate | 15g |
| Sodium alginate | 15g |
Oseltamivir phosphate and sodium alginate are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, the sodium alginate of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 2: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight |
| Oseltamivir phosphate | 15g |
| Sodium alginate | 1.5g |
Oseltamivir phosphate and sodium alginate are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, the sodium alginate of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 3: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight |
| Oseltamivir phosphate | 15g |
| Sodium alginate | 150g |
Oseltamivir phosphate and sodium alginate are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, the sodium alginate of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 4: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight/g |
| Oseltamivir phosphate | 15 |
| Sodium alginate | 15 |
| Sorbitol | 150 |
| Sodium citrate | 3 |
| Xanthan gum | 1 |
Oseltamivir phosphate and sodium alginate and other adjuvant are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, sodium alginate and other adjuvant of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 5: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight/g |
| Oseltamivir phosphate | 15 |
| Sodium alginate | 10 |
| Sorbitol | 150 |
| Sodium citrate | 3 |
| Xanthan gum | 3 |
| Sodium benzoate | 1 |
| Saccharin sodium | 0.15 |
Oseltamivir phosphate and sodium alginate and other adjuvant are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, sodium alginate and other adjuvant of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 6: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight/g |
| Oseltamivir phosphate | 15 |
| Sodium alginate | 1.5 |
| Sorbitol | 750 |
| Mannitol | 750 |
| Sodium citrate | 0.15 |
| Xanthan gum | 0.15 |
| Sodium benzoate | 0.15 |
| Saccharin sodium | 0.15 |
Oseltamivir phosphate and sodium alginate and other adjuvant are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, sodium alginate and other adjuvant of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 7: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight/g |
| Oseltamivir phosphate | 15 |
| Sodium alginate | 150 |
| Sorbitol | 500 |
| Sodium citrate | 150 |
| Xanthan gum | 0.15 |
| Sodium benzoate | 1 |
| Saccharin sodium | 0 |
Oseltamivir phosphate and sodium alginate and other adjuvant are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, sodium alginate and other adjuvant of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 8: the preparation of oseltamivir phosphate solid composite medicament
| Composition | Weight/g |
| Oseltamivir phosphate | 15 |
| Sodium alginate | 75 |
| Lactose | 75 |
| Sodium citrate | 30 |
| Xanthan gum | 30 |
| Sodium benzoate | 15 |
| Saccharin sodium | 1.5 |
Oseltamivir phosphate and sodium alginate and other adjuvant are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, sodium alginate and other adjuvant of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Embodiment 9: the preparation of oseltamivir phosphate solid composite medicament
Oseltamivir phosphate and sodium alginate and other adjuvant are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, sodium alginate and other adjuvant of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
The preparation of comparative example 1, oseltamivir phosphate granula
| Composition | Weight |
| Oseltamivir phosphate | 20g |
| Sucrose | 568g |
| Polyvidone k30 | 12g |
| Total amount | 600g |
Oseltamivir phosphate and other adjuvant were all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate, polyvidone k30 and the sucrose of recipe quantity, by the equivalent method mix homogeneously that progressively increases; With 40v/v% ethanol water system soft material, cross 14 mesh sieves and granulate, wet granular is placed 45-60 ℃ of oven for drying after, through 14 mesh sieve granulate, remove fine powder with No. 5 sieve sieves after, mensuration granule drug content and moisture are confirmed loading amount; Above-mentioned granule branch is installed in the plastic bottle, and every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
The preparation of comparative example 2, oseltamivir phosphate granula
| Composition | Weight |
| Oseltamivir phosphate | 15g |
The oseltamivir phosphate branch that directly will pulverize 100 mesh sieves installs in the plastic bottle, and every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
The preparation of comparative example 3, oseltamivir phosphate granula
| Composition | Weight/g |
| Oseltamivir phosphate | 15 |
| Sorbitol | 150 |
| Sodium citrate | 3 |
| Xanthan gum | 3 |
| Sodium benzoate | 1 |
| Saccharin sodium | 0.15 |
Oseltamivir phosphate and other adjuvant are all pulverized 100 mesh sieves, accurately took by weighing oseltamivir phosphate and other adjuvant of recipe quantity, mix homogeneously; Divide to install in the plastic bottle, every bottle of phosphoric acid Oseltamivir 600mg promptly gets.
Preparation example 1: the preparation of oseltamivir phosphate composition of liquid medicine (suspension)
Get embodiment 1-9 and comparative example 1-3 gained solid composite medicament respectively, 1: 5,1: 10,1: 20 the mixed of weight ratio of pressing solid and water (or water-bearing media) shakes up, and processes suspension.The numbering of the carrier of this suspension, configuration proportion and gained suspension is distinguished as follows:
Annotate above symbol, the for example composition of liquid medicine that is mixed with 1: 10 ratio of solid-to-liquid ratio with solid composite medicament and 30% sucrose solution of embodiment 1 of " Suc-1 " expression; The composition of liquid medicine that " sWat-c1 " expression is mixed with 1: 20 ratio of solid-to-liquid ratio with the solid composite medicament and the water of comparative example 1, other symbol also has similar meaning.
Test Example 1: oseltamivir phosphate liquid stabilising property investigation
Get the suspension of respectively filling a prescription that obtains in the preparation example 1, in 40 ℃ of calorstats, placed 15 days.To each sample,, investigate each sample oseltamivir phosphate remnants rate (%) in the time of 15 days respectively at 0 day (before 40 ℃ of calorstats are placed) and (after 40 ℃ of calorstats are placed) sampling in 15 days.The remaining rate of oseltamivir phosphate (%) is calculated as follows:
In this experiment, get each specimen and suitably dilute, filter; Then list of references [Hu Hairong, the content of measuring the oseltamivir phosphate crude drug etc., HPLC also detects its related substance; The West China pharmaceutical journal; 2009 the 6th phases] record the HPLC method [used basic chromatographic condition is: use the LunaC8 post, mobile phase is 0.05molL-1 potassium dihydrogen phosphate-acetonitrile-methanol (620: 245: 135), and flow velocity is 1.2mLmin-1; Column temperature is 50 ℃, and the detection wavelength is 207nm] measure in each sample the remaining percentage amounts of oseltamivir phosphate.The result of each sample remaining rate of oseltamivir phosphate (%) in the time of 15 days sees the following form.
Claims (7)
1. a solid composite medicament wherein comprises oseltamivir phosphate, the sodium alginate of treatment or prevention effective dose and the acceptable excipient of choosing wantonly of one or more pharmacy, wherein:
The weight ratio of sodium alginate and oseltamivir phosphate is (0.1～10): 1;
The acceptable excipient of said pharmacy is selected from filler, buffer agent, thickening agent, antiseptic, flavoring agent, sweeting agent;
Said filler is selected from sorbitol, mannitol, lactose, sucrose;
Said buffer agent is selected from sodium citrate, potassium citrate, sodium lactate, sodium succinate;
Said thickening agent is selected from xanthan gum, sodium carboxymethyl cellulose.
2. according to the solid composite medicament of claim 1, wherein comprise:
Oseltamivir phosphate 1 weight portion,
Sodium alginate 0.1～10 weight portion,
Sorbitol and/or mannitol and/or lactose 0.1～100 weight portion.
3. according to the solid composite medicament of claim 1, wherein comprise:
Oseltamivir phosphate 1 weight portion,
Sodium alginate 0.1～10 weight portion,
Sorbitol and/or mannitol and/or lactose 0.1～100 weight portion,
Sodium citrate 0.01～10 weight portion.
4. according to the solid composite medicament of claim 1, wherein comprise:
5. according to the solid composite medicament of claim 1, wherein comprise:
6. according to the solid composite medicament of claim 1, wherein comprise:
7. each solid composite medicament of claim 1-6 is in the purposes of preparation in the liquid medicine for oral use.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100367962A CN102144962B (en) | 2011-02-12 | 2011-02-12 | Powdered osletamirvir phosphate medicinal composition |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011100367962A CN102144962B (en) | 2011-02-12 | 2011-02-12 | Powdered osletamirvir phosphate medicinal composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2010143207A1 (en) * | 2009-06-11 | 2010-12-16 | Rubicon Research Private Limited | Taste-masked oral formulations of influenza antivirals |
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| WO2010143207A1 (en) * | 2009-06-11 | 2010-12-16 | Rubicon Research Private Limited | Taste-masked oral formulations of influenza antivirals |
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