CN1535680A - Abidor inclusion compound - Google Patents
Abidor inclusion compound Download PDFInfo
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- CN1535680A CN1535680A CNA031092748A CN03109274A CN1535680A CN 1535680 A CN1535680 A CN 1535680A CN A031092748 A CNA031092748 A CN A031092748A CN 03109274 A CN03109274 A CN 03109274A CN 1535680 A CN1535680 A CN 1535680A
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- abiduoer
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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Abstract
The present invention relates to a molecular inclusion compound containing abiduoir and cyclodextrin or its derivative, its preparation method and application for preparing medicine preparation. The preparation of said abiduoir inclusion compound is aimed at raising its water solubility and stability, and said inclusion compound can be used as an initial raw material or one compound for preparing intestinal tract administration on non-intestinal administration preparation.
Description
Technical field
The present invention relates to a kind of new Abiduoer and the molecular clathrate of cyclodextrin or its derivant, and the preparation method of this clathrate and their application in pharmaceutical preparation.
Background technology
Arbidol HCl (Arbidol hydrochloride) is a kind of novel antiviral medicine.It is the most remarkable to the antiviral activity with A, the antigenic influenza virus of Type B, can suppress A, Type B influenza virus duplicating in cell culture medium by selectivity.Abiduoer has immunoregulation effect simultaneously, can induce the generation interferon, and activating macrophage improves the resistance of body to viral infection, is to be used for the treatment of the influenza that A, Type B virus cause and the novel antiviral medicine of acute respiratory viral infection.
Arbidol HCl is water-soluble hardly, dissolubility only is 0.0024g/100ml (25 ± 2 ℃), its water-insoluble has limited the exploitation of its liquid preparation such as injection, the preparation that has gone on the market or studied mainly is its tablet and capsule, existing preparation technique still can't solve its water-insoluble shortcoming, therefore the oral formulations bioavailability is low, has influenced the exploitation of intestinal canal administration and parenterai administration dosage form.
Summary of the invention
The objective of the invention is to improve the water solublity of arbidol HCl, it can be developed to be liquid preparation by preparation Abiduoer clathrate, thus adaptation different needs clinically.Also can improve simultaneously interior absorption of body of arbidol HCl solid preparation, improve its bioavailability.
Cyclodextrin has the ring-type hollow circle tube structure of both ends open, multiple homologue is arranged, common cyclodextrin is by 6,7,8 glucose molecules, by α-1, the cyclic compound that 4 glycosidic bonds are formed by connecting, be referred to as respectively α-, β-and gamma-cyclodextrin, its cavity size difference, be followed successively by alpha-cyclodextrin＜beta-schardinger dextrin-＜gamma-cyclodextrin, when the size of drug molecule, when shape is suitable, can enter in the cyclodextrin cavity, form the unimolecule clathrate.In clathrate, cyclodextrin is as host molecule, and drug molecule is as enclosed molecule, and the two forms clathrate under the effect of one or more power such as Van der Waals force, hydrogen bond, electrostatic attraction.The cavity inside of cyclodextrin is made of c h bond and ehter bond, is hydrophobicity, more helps the enclose of hydrophobic drug; Cavity outside and porch are rich in hydrophilic, and the clathrate dissolubility of formation is significantly improved.
Arbidol HCl is 6-bromo-4-(dimethyl aminomethyl)-5-hydroxyl-1-methyl-2 (benzene sulfidomethyl)-1H-indole-3-carboxylic acid carbethoxy hydrochloride monohydrate, contains an indole ring and a phenyl ring in the molecule, and molecular weight is 531.89.Owing to do not have the too big group of volume in the arbidol HCl molecule, molecular weight neither be very big, β that can be bigger with the molecule cavity-and gamma-cyclodextrin to form mol ratio be 1: 1 clathrate, and for the less alpha-cyclodextrin of cavity internal diameter, a drug molecule then needs the host molecule more than 2 could form stable clathrate.The arbidol HCl molecule is strong-hydrophobicity, and behind cyclodextrin inclusion compound, its dissolubility is significantly improved, and for example in 1.23% HP-aqueous solution, its dissolubility is increased to 0.25g/100ml by 0.0024g/100ml, has improved 100 times.
In Abiduoer clathrate of the present invention, contain active component Abiduoer and inclusion agents cyclodextrin or its derivant
Wherein cyclodextrin comprise α-, β-, gamma-cyclodextrin.
Cyclodextrin derivative comprise ethoxy-β-, the 2-hydroxy propyl-Beta-, the 3-hydroxy propyl-Beta-, 2, the 3-hydroxy propyl-Beta-, dimethyl-β-, trimethyl-β-, glucityl-α-, glucityl-β-, didextrose base-β-, sulphonyl butyl-Benexate Hydrochloride.
The mol ratio of arbidol HCl and cyclodextrin or its derivant is 1: 1～10 among the present invention.
The preparation of arbidol HCl clathrate can be adopted following distinct methods among the present invention, and the inclusion agents less for water solublity should adopt saturated water solution method; The inclusion agents bigger for water solublity should adopt solution-paddling process; And polishing is applicable to any inclusion agents.
Saturated water solution method: cyclodextrin or its derivant are made saturated aqueous solution, add an amount of acidic materials again, mol ratio according to Abiduoer and inclusion agents, dissolve Abiduoer with little lower alcohol, the enclosed molecule medicine is added above-mentioned saturated acid solution, stirring makes the enclosed molecule medicine by abundant enclose, and precipitate leaches and with an amount of lower alcohol washing after drying, gets the Abiduoer clathrate.
Supercritical ultrasonics technology: according to the said method Abiduoer with after inclusion agents is mixed, with electronics or the mechanical agitation power in the alternative above-mentioned saturated water solution method of ultrasound wave, with ultrasonic disruption instrument or ultrasonic washing unit, select suitable intensity, ultrasonic appropriate time, replace mixing power, will separate out the method that precipitates as above and handle and promptly get the Abiduoer clathrate.
Solution-paddling process: for dissolubility in water bigger cyclodextrin or its derivant, can in unsaturated cyclodextrin or its derivant aqueous solution, add an amount of acidic materials, add the enclosed molecule medicine, form clathrate through stirring.
In above-mentioned inclusion agents, α-, γ-, ethoxy-β-, the 2-hydroxy propyl-Beta-, the 3-hydroxy propyl-Beta-, 2, the 3-hydroxy propyl-Beta-, dimethyl-β-, trimethyl-β-, glucityl-α-, glucityl-β-, didextrose base-β-, sulphonyl butyl-beta-schardinger dextrin-, the dissolubility in water is bigger, is particularly useful for solution-paddling process.
Spray drying method: if the Abiduoer clathrate that makes is soluble in water, the chance thermal property is more stable again, and available spray drying method obtains solid clathrates, and characteristics are baking temperature height, and heated time is short, the productive rate height.
Freeze-drying: as the clathrate that makes is soluble in water, is difficult for separating out crystalline deposit, or when heat drying, easily decompose, variable color, available freeze-drying obtains solid clathrates, makes the clathrate profile loose, solubility property is good, can be made into injectable powder.
Polishing: get 2～5 times of water gagings of cyclodextrin or its derivant adding and grind well, add an amount of acidic materials again, mol ratio according to Abiduoer and inclusion agents, add the enclosed molecule medicine, fully grind to form pasty state in the self-grind machine, use the appropriate solvent cleaning, drying after the cold drying, promptly get the Abiduoer clathrate.
The Abiduoer clathrate can be used as a kind of initiation material or a kind of composition, is used to prepare intestinal canal administration or non-intestinal drug delivery agent.
The specific embodiment
In the clathrate of Abiduoer and cyclodextrin or the generation of its derivant, preferred Abiduoer-Benexate Hydrochloride, the preferred saturated solution method of its preparation method.
The preparation of arbidol HCl-Benexate Hydrochloride can be adopted saturated water solution method.(0.0022～0.022mol) adds water 150～1500ml, puts in 40～60 ℃ of water-baths to make its dissolving become saturated aqueous solution, adds an amount of tartaric acid again, makes solution PH reach 4.0～5.0 with beta-schardinger dextrin-2.5～25g; After arbidol HCl 1.17g (0.0022mol) added small amount of methanol or dissolve with ethanol, it is added constant temperature stirred 1～4 hour in beta-schardinger dextrin-saturated aqueous solution, precipitate is leached and with amount of methanol or washing with alcohol after drying.
Arbidol HCl and water soluble Beta-cyclodextrin or its derivant inclusion method preferred solution-paddling process, general preparation method is as follows:
Take by weighing 0.018～0.18mol cyclodextrin, put into the 400ml distilled water, stirring and dissolving adds an amount of tartaric acid again, makes solution PH reach 4.0～5.0; Other takes by weighing arbidol HCl 10g (0.018mol), adds in the above-mentioned cyclodextrin solution, and mixed liquor stirred 10～60 minutes with magnetic force or electronic stirring means, and solution is clarified gradually, promptly gets arbidol HCl-cyclodextrin clathrate solution.The solution that makes in order to the top method carries out spray drying or lyophilizing, can obtain solid, shaped arbidol HCl-cyclodextrin clathrate.
Embodiment one: saturated water solution method prepares arbidol HCl-Benexate Hydrochloride
Take by weighing beta-schardinger dextrin-5 grams (0.0044mol), place the 1000ml three-necked bottle with electric mixing device, add 350mg tartaric acid again, adding distil water 600ml puts 40 ℃ of water-baths and makes its dissolving; Take by weighing arbidol HCl 1.17 gram (0.0022mol), with the 15ml dissolve with methanol, and it is splashed in the beta-schardinger dextrin-saturated solution, constant temperature stirred 4 hours, and reactant liquor staticly settles, sucking filtration, and precipitate washs with amount of methanol.In 45 ℃ of vacuum dryings, promptly.
Get arbidol HCl-Benexate Hydrochloride 0.5g (hydrochloric Abiduoer 0.052mg) and arbidol HCl 0.052mg that this method obtains, add water 10ml respectively, shake well dissolving after-filtration, get filtrate and survey its trap with ultraviolet spectrophotometry, and calculate its dissolubility and be respectively 0.14g/100ml and 0.0024g/100ml, promptly the dissolubility of Abiduoer has had and has significantly improved behind the enclose.
Embodiment two: supercritical ultrasonics technology prepares arbidol HCl-Benexate Hydrochloride
Take by weighing beta-schardinger dextrin-10 gram (0.0088mol), adding distil water 600ml adds 350mg tartaric acid again, and container was put in the ultrasonic disruption instrument ultrasonic 5 minutes, makes its dissolving; Take by weighing arbidol HCl 1.17 gram (0.0022mol), with the 15ml dissolve with methanol, and it is splashed in the beta-schardinger dextrin-saturated solution, continued ultrasonic 20 minutes, reactant liquor staticly settles, sucking filtration, and precipitate washs with amount of methanol.In 45 ℃ of vacuum dryings, promptly.
Embodiment three: polishing prepares arbidol HCl-Benexate Hydrochloride
11.7mg tartaric acid is dissolved in the 20ml water, together places grinder with 10 gram (0.0088mol) beta-schardinger dextrin-s then.1.17 gram (0.0022mol) arbidol HCls are dissolved in the 15ml methanol, add grinding machine for grinding and become pasty state, at 45 ℃ of vacuum dryings, wash with amount of methanol, sucking filtration in 45 ℃ of vacuum dryings, pulverizing, promptly gets arbidol HCl-Benexate Hydrochloride.
Embodiment four: solution-paddling process prepares arbidol HCl-gamma-cyclodextrin clathrate
(1) takes by weighing 46.69g (0.036mol) gamma-cyclodextrin, put into the 400ml distilled water, add 235mg tartaric acid again, stirring and dissolving;
(2) take by weighing arbidol HCl 10g (0.018mol) in addition, add in the above-mentioned gamma-cyclodextrin solution;
(3) mixed liquor stirred 20 minutes with the magnetic agitation method, and solution is clarified gradually, filtered, and filtrate is arbidol HCl-gamma-cyclodextrin inclusion complex in solution.
(4) solution that makes in order to the top method carries out spray drying or lyophilizing, can obtain solid, shaped arbidol HCl-gamma-cyclodextrin clathrate.
Arbidol HCl-gamma-cyclodextrin clathrate the dissolubility that makes with this method is 2.06g/100ml.
Embodiment five: solution-paddling process prepares arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion solution
(1) takes by weighing 49.18g (0.036mol) HP-, put into the 400ml distilled water, add 235mg tartaric acid again, stirring and dissolving;
(2) take by weighing arbidol HCl 10g (0.018mol) in addition, add in the above-mentioned HP-solution;
(3) mixed liquor stirred 20 minutes with the magnetic agitation method, and solution is clarified gradually, promptly gets arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion solution.
(4) solution that makes in order to the top method carries out spray drying or lyophilizing, can obtain solid, shaped arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion.
Arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion the dissolubility that makes with this method is 2.23g/100ml.
Embodiment six: solution-paddling process prepares arbidol HCl-DM-inclusion complex in solution
(1) take by weighing 40.72g (0.036mol) 2, the 6-DM-is put into the 400ml distilled water, adds 235mg tartaric acid again, stirring and dissolving;
(2) take by weighing arbidol HCl 10g (0.018mol) in addition, add in the above-mentioned HP-solution;
(3) mixed liquor stirred 20 minutes with the magnetic agitation method, and solution is clarified gradually, promptly gets arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion solution.
(5) solution that makes in order to the top method carries out spray drying or lyophilizing, can obtain solid, shaped arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion.
Arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion the dissolubility that makes with this method is 2.18g/100ml.
Embodiment seven: the preparation of arbidol HCl-Benexate Hydrochloride tablet
(1) preparation of arbidol HCl-Benexate Hydrochloride is with embodiment one.
(2) above-mentioned arbidol HCl-Benexate Hydrochloride is prepared into tablet (every hydrochloric Abiduoer 50mg), it is as follows to fill a prescription:
Arbidol HCl-beta-schardinger dextrin-bag 312mg
Compound
Starch 150.4mg
Pregelatinized Starch 75.2mg
Crospolyvinylpyrrolidone 16.8mg
2% hydroxypropyl emthylcellulose, 60% second is an amount of
Alcoholic solution
Magnesium stearate 5.6mg
Gross weight 560mg
(3) with arbidol HCl-Benexate Hydrochloride, starch, pregelatinized Starch, crospolyvinylpyrrolidone mix homogeneously, add 2% hydroxypropyl emthylcellulose, 60% alcoholic solution system soft material, and make the granule of about 20 order sizes, dry back adds the magnesium stearate tabletting.
Embodiment eight: the sodium chloride injection of preparation arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion
(1) arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion formulations prepared from solutions process is with (1), (2), (3) of embodiment five;
(2) take by weighing sodium chloride for injection 75g, add water to 1L, stirring and dissolving adds the 1g transfusion and uses active carbon, heats little boiling 15 minutes, takes off charcoal.
(3) sodium chloride liquid is poured in the inclusion complex in solution, and moisturizing is transferred PH=4.0～7.0 to 8L with hydrochloric acid and the 0.05N sodium hydroxide of 0.05N, and moisturizing adds the 1g active carbon to 10L, and 40 ℃ are incubated 20 minutes.
(4) solution is crossed buchner funnel respectively and 0.45 μ m microporous filter membrane carries out coarse filtration, fine straining, carries out fill (100ml/ bottle) then, and 115 ℃, 30 minutes pressure sterilizings promptly.
Embodiment nine: preparation arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion aseptic powder injection
(1) indoor in the sterile working, take by weighing 49.18g (0.036mol) HP-, add 525mg tartaric acid again, be dissolved in water to 900ml, add the 1g transfusion and use active carbon, be heated with stirring to 80 ℃, be incubated 15 minutes, filtering decarbonization.
(2) take by weighing 10g (0.018mol) arbidol HCl, add in the HP-solution.
(3) the magnetic agitation mixing material is about 20 minutes, and solution is clarified gradually, promptly gets arbidol HCl-hydroxypropyl-beta-cyclodextrin inclusion solution.
(4) moisturizing adds the 1g active carbon to 1000ml, and 40 ℃ are incubated 20 minutes.
(5) solution is crossed buchner funnel respectively and 0.22 μ m microporous filter membrane carries out coarse filtration, fine straining, is sub-packed in the cillin bottle of 10ml (10ml/ bottle), and the lyophilization gland promptly.
Claims (9)
1, a kind of Abiduoer clathrate is characterized by: contain active component Abiduoer and inclusion agents cyclodextrin or its derivant.
2, Abiduoer clathrate according to claim 1 is characterized by: the mol ratio of Abiduoer and cyclodextrin or its derivant is 1: 1～10.
3, Abiduoer clathrate according to claim 1 is characterized by: the inclusion agents cyclodextrin comprise α-, β-, gamma-cyclodextrin; The inclusion agents cyclodextrin derivative comprises: ethoxy-β-, the 2-hydroxy propyl-Beta-, the 3-hydroxy propyl-Beta-, 2, the 3-hydroxy propyl-Beta-, dimethyl-β-, trimethyl-β-, glucityl-α-, glucityl-β-, didextrose base-β-, sulphonyl butyl-beta-schardinger dextrin-.
4, according to claim 1, it is characterized by: preferred Abiduoer-Benexate Hydrochloride.
5, a kind of preparation method of Abiduoer clathrate, it is characterized by the saturated water solution method of Abiduoer-Benexate Hydrochloride: cyclodextrin or its derivant are made saturated aqueous solution, mol ratio according to Abiduoer and inclusion agents, dissolve Abiduoer with little lower alcohol, Abiduoer is added above-mentioned saturated aqueous solution, stirring makes Abiduoer by abundant enclose, and precipitate leaches and with an amount of lower alcohol washing after drying, gets the Abiduoer clathrate.
6, a kind of preparation method of Abiduoer clathrate, it is characterized by solution-paddling process: for dissolubility in water bigger cyclodextrin or its derivant, can in unsaturated cyclodextrin or its derivant aqueous solution, add Abiduoer, form clathrate through stirring.
7, preparation method according to claim 6 is characterized by: cyclodextrin or its derivant have good water-solubility, can be α-, γ-, ethoxy-β-, the 2-hydroxy propyl-Beta-, the 3-hydroxy propyl-Beta-, 2, the 3-hydroxy propyl-Beta-, dimethyl-β-, trimethyl-β-, glucityl-α-, glucityl-β-, didextrose base-β-, sulphonyl butyl-beta-schardinger dextrin-.
8, a kind of preparation method of Abiduoer clathrate, it is characterized by polishing: get 2～5 times of water gagings of cyclodextrin or its derivant adding and grind well, mol ratio according to Abiduoer and inclusion agents, add the Abiduoer medicine, put and fully grind to form pasty state in the grinder, with the appropriate solvent washing, drying promptly gets the Abiduoer clathrate.
9, a kind of purposes of Abiduoer clathrate is characterized by: it can be used as a kind of initiation material or a kind of composition is used to prepare intestinal canal administration or non-intestinal drug delivery agent.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031092748A CN100344283C (en) | 2003-04-08 | 2003-04-08 | Abidor inclusion compound |
| PCT/CN2004/000322 WO2004089338A1 (en) | 2003-04-08 | 2004-04-08 | A arbidol clathrate and its preparation process and the use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031092748A CN100344283C (en) | 2003-04-08 | 2003-04-08 | Abidor inclusion compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1535680A true CN1535680A (en) | 2004-10-13 |
| CN100344283C CN100344283C (en) | 2007-10-24 |
Family
ID=33136781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031092748A Expired - Fee Related CN100344283C (en) | 2003-04-08 | 2003-04-08 | Abidor inclusion compound |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN100344283C (en) |
| WO (1) | WO2004089338A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100367957C (en) * | 2005-11-29 | 2008-02-13 | 沈阳中海生物技术开发有限公司 | Abiduoer and its salts prepns. for vena administration, and its preparing method |
| CN102357093A (en) * | 2011-09-01 | 2012-02-22 | 湖北丽益医药科技有限公司 | Medicinal composition of methanesulfonic acid arbidol oral solid preparation |
| CN103211825A (en) * | 2013-04-19 | 2013-07-24 | 黄华 | Novel celecoxib composition and preparation process thereof |
| CN111956616A (en) * | 2020-09-08 | 2020-11-20 | 山西振东泰盛制药有限公司 | Arbidol hydrochloride composite dry powder preparation, spray, gel and preparation method thereof |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2411942C2 (en) * | 2009-05-05 | 2011-02-20 | Общество с ограниченной ответственностью "ЭкоБиоФарм" | Pharmaceutic composition including arbidol in composition of phospholipid nanoparticles |
| CN110575550A (en) * | 2019-08-13 | 2019-12-17 | 大梆(沈阳)动物保健有限公司 | Method for shielding bad smell of compound traditional Chinese medicine for livestock |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2008004C1 (en) * | 1986-06-25 | 1994-02-28 | Центр по химии лекарственных средств - ВНИХФИ | Prophylactic and curative agent for treating flu virus b |
| RU2033157C1 (en) * | 1987-12-16 | 1995-04-20 | Центр по химии лекарственных средств | Drug possessing interferon-inducing and immunomodulating (immunostimulating) activity |
-
2003
- 2003-04-08 CN CNB031092748A patent/CN100344283C/en not_active Expired - Fee Related
-
2004
- 2004-04-08 WO PCT/CN2004/000322 patent/WO2004089338A1/en active Application Filing
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100367957C (en) * | 2005-11-29 | 2008-02-13 | 沈阳中海生物技术开发有限公司 | Abiduoer and its salts prepns. for vena administration, and its preparing method |
| CN102357093A (en) * | 2011-09-01 | 2012-02-22 | 湖北丽益医药科技有限公司 | Medicinal composition of methanesulfonic acid arbidol oral solid preparation |
| CN102357093B (en) * | 2011-09-01 | 2013-03-20 | 湖北丽益医药科技有限公司 | Medicinal composition of methanesulfonic acid arbidol oral solid preparation |
| CN103211825A (en) * | 2013-04-19 | 2013-07-24 | 黄华 | Novel celecoxib composition and preparation process thereof |
| CN103211825B (en) * | 2013-04-19 | 2014-07-30 | 北京博爱旺康医药科技有限公司 | Novel celecoxib composition and preparation process thereof |
| CN111956616A (en) * | 2020-09-08 | 2020-11-20 | 山西振东泰盛制药有限公司 | Arbidol hydrochloride composite dry powder preparation, spray, gel and preparation method thereof |
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| Publication number | Publication date |
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| CN100344283C (en) | 2007-10-24 |
| WO2004089338A1 (en) | 2004-10-21 |
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