CN1572298A - Arbidol containing compound preparation - Google Patents
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- CN1572298A CN1572298A CNA2004100371648A CN200410037164A CN1572298A CN 1572298 A CN1572298 A CN 1572298A CN A2004100371648 A CNA2004100371648 A CN A2004100371648A CN 200410037164 A CN200410037164 A CN 200410037164A CN 1572298 A CN1572298 A CN 1572298A
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Abstract
The present invention relates to a compound preparation containing antiviral drug arbidol, which is especially adapted to respiratory tract infection disease caused by virus. During the respiratory tract infection period, the patient has the discomfort symptoms of fever and nose stuff, therefore, the anti influenza compound preparation on the invention also includes one, two or three of the ibuprofen, alcaine pseudoephedrine, and dextromethorphan hydrobromide on the basis of including alcaine arbidol, and is then added with take orally preparation medicinal adjuvant to make take orally solid dosage forms. The medical effect experiment shows that the cooperation of the active components in the compound preparation is well, and the preparation is convenient in used by patient.
Description
Technical field
The present invention relates to the compound preparation of antiviral drugs arbidol HCl, particularly the compound preparation of its treatment influenza and various symptoms thereof.
Background technology
Influenza (influenza, be called for short influenza) is the acute respiratory infectious disease that is caused by influenza virus, is one of main public health problem of facing of the mankind.According to statistics, the sickness rate in influenza every year is 10%～30%, and the outstanding feature of its epidemiology is: outburst suddenly, rapid spread is broadcast and wide.Influenza pandemic has certain seasonality.Northern China often betides winter, and mostly occurs in two seasons of summer in winter in south.The sickness rate height of influenza, the general susceptible of crowd.China is the district occurred frequently of influenza, and 20th century 4 times are global has been very popular 3 times to originate from China.Two kinds of glycoprotein projections are arranged, i.e. hemagglutinin (HA) and neuraminidase (NA) on the influenza virus.According to the antigenicity difference, influenza virus is divided into first, second, the third 3 types.Influenza A virus often occurs with popular form, can cause worldwide being very popular; The B-mode influenza part that often causes is broken out; Third type mainly occurs to distribute form.Because the influenza antigen variation is very fast, so the mankind can't obtain persistent immunity.The influenza clinical symptoms is heavier, and onset is rapid, the complication rate height, and can cause death, dead person mostly is old asthenia, young many diseases greatly or chronic underlying diseases person is arranged.Above-mentioned crowd is carried out the main method that vaccination is the control influenza.The crowd can produce immunity by infecting or inoculating, but new variant viral strain be there is no protective effect.Think that at present the resisiting influenza virus treatment is the important means of influenza control.Due to illness poison has antigenic variability, and the acute respiratory viral infection has multi-drug resistant in addition, so need a fully safe treatment and prevent the vaccine of these diseases.Because of the reason on the source, gamma interferon is negated, so chemicals occupies very consequence on the treatment influenza.Up to now, adamantane derivant amantadine and rimantadine as antiviral drugs in wide clinical application, but its field of activity narrower (only effective) to A type influenza virus, and have side reaction, and along with its drug resistance of clinical practice also increases simultaneously.
Arbidol HCl (Arbidol) is a new antiviral drugs, is the new antiviral drug of former Soviet Union's pharmaceutical chemistry research center development, is used to prevent and treat influenza and other acute respiratory virus infection in Russian Initial Public Offering in 1993.
Arbidol HCl is the most remarkable to the antiviral activity with A, the antigenic influenza virus of Type B, its effect and 2, and the activation of 5-oligoadenylate synthetase is relevant.The Abiduoer selectivity suppresses A, Type B influenza virus duplicating in cell culture medium.Early stage at virus replication, Abiduoer has shown the effect to specificity virus, the fusion of inhibition and cell membrane and viral lipid film.
Abiduoer has immunoregulation effect simultaneously, can induce the generation interferon, and the phagocytosis of macrophage is had significant activation, and multi-form cell immune response is had significant stimulation.
Arbidol HCl is used to prevent and treat influenza and other acute respiratory virus infection, has following characteristics: 1, to influenza virus A type and B-mode all effective; 2, existing therapeutical effect also has preventive effect; 3, have the direct dual function that suppresses virus and induce endogenous interferon concurrently; 4, Orally-administrable, easy to use; 5. be non-nucleosides compound, low, the well-tolerated of toxicity.
The clinical research result reports that arbidol HCl is a kind of efficient medicine of preventing and treating first type and influenza B and other acute respiratory virus infection.Can the protect from infection generation of infectious-related complication; Reduce the deterioration rate of the original chronic disease of influenza patient; In the conjoint therapy of the complication pneumonia of influenza and other acute respiratory infection, use this product, can quicken recovery from illness, reduce antibiotic dosage.Do not see significant side effects in the research, and well-tolerated.
Another extensive clinical research report after 2000 influenza patients take arbidol HCl, can shorten the duration of heating, mucositis syndrome and other clinical symptoms and prevent the generation of influenza infectious-related complication.
In sum, arbidol HCl is a kind of to treatment and flu-prevention and the very effective antiviral drugs of upper respiratory tract infection.Except that antiviral therapy, also should carry out symptomatic treatment at the clinical symptoms of influenza.General 1～3 day of incubation period of influenza, the shortest a few hours.Typical case's influenza mainly contains following symptom: the anxious fear of cold hyperpyrexia that rises, and weak, headache, general pain, pharyngeal dried pain can have nasal obstruction, watery nasal discharge, sneeze, dry cough, pharyngeal visible hyperemia, pulmonary's audible rhonchi.The after heat on the 3rd～4 of generating heat is moved back, but upper airway symptoms and about weak sustainable 2 weeks.According to influenza clinical diagnosis and treatment guide (draft) that Chinese Medical Association's respiratory disease credit meeting is formulated, the clinical symptoms of influenza and common cold is differentiated and is seen Table 1.
The clinical symptoms of table 1 influenza and common cold is differentiated
Symptom
Nasal obstruction, chest are not
Kind general fatigue, complication
Fever and headache sneeze, suitable and cough
The pain weakness
Pharyngalgia is coughed
Common slightly extremely
Rare slight common rare
The flu moderate
Typical case's disease
Shape often is a bronchus
Go out in early days
Hyperpyrexia is common, can scorching, lung
Influenza is significantly common and existing, significantly, and sometimes
(39～40 can be serious scorching, but prestige
Serious sustainable with
℃) lasting side of body life
2～3 weeks
3～4 days
By table 1 as seen, heating, headache, whole body pain, tired weakness, chest discomfort and cough are the common sympton of influenza, in addition sometimes also can be with symptoms such as nasal obstruction, sneeze, pharyngalgia, mostly the compound recipe coldrex of using clinically is the above-mentioned various symptoms at common cold or influenza at present, and has antivirus action, the compound recipe coldrex that can fundamentally treat influenza is fewer, mostly its antiviral ingredients is amantadine, it only has certain effect to influenza A, its curative effect does not affirm that amantadine also has certain side effect simultaneously.Thus, press for clinically a kind of can at the cause of disease, again can mitigation symptoms the compound recipe cold medicine for the treatment of both the principal and secondary aspects of a disease.
Summary of the invention
The present invention seeks to form compound preparation with a kind of, two or three medicine in antipyretic analgesic ibuprofen, the congested medicine pseudoephedrine hydrochloride of alleviation nasal mucosa, the antitussive dextromethorphan hydrobromide, be used for the treatment of the different symptoms of influenza with resisiting influenza virus medicine arbidol HCl.
Arbidol HCl capsule (100mg) clinical trial proves, arbidol HCl is taken in 36 hours of heating paresthesia are arranged, and each 200 milligrams, every day 3 times, can play the effect of treatment influenza.Therefore, the medicine of forming compound preparation with arbidol HCl should have the suitable half-life, can administration every day 3 times.Putting before this, these medicines also should have good effect, the little advantage of untoward reaction.
The nonsteroidal antiinflammatory drug ibuprofen has tangible antipyretic effect, has been used to be grown up for the OTC medicine by FDA approval and child analgesic more than 6 months.The absorption of ibuprofen is complete rapidly, and oral administration biaavailability is 80%.Peak concentration appears at the back 1～2h that takes medicine, and 99% medicine combines with plasma protein, and the half-life is 1～2h.Instructions of taking each 200～400mg that is grown up, every day 3～4 times; Child 10～20mg/kg, per 6 hours 1 time.The clinical research result shows, ibuprofen is compared with acetaminophen to have analgesic effectively, and acting duration is long, and oral absorption is rapid, the advantage that untoward reaction is few, so the present invention selects ibuprofen as the antipyretic analgesics component.
Pseudoephedrine hydrochloride is the nasal mucosa vessels contracting agent, can alleviate the congested and nasal obstruction that causes of nasal mucosa vessels, watery nasal discharge and does not have cardiac stimulus to cause cardiac muscle and shrink peripheral blood vessel, the untoward reaction that causes elevation of the blood pressure.Pseudoephedrine hydrochloride has been widely used in multiple compound recipe coldrex, and instructions of taking is the each 30mg of adult, 3 times on the one; 2～5 years old each 10mg of child, 3 times on the one; 6～12 years old each 15mg of child, 3 times on the one.
Dextromethorphan hydrobromide is the maincenter cough medicine, is applicable to the dry cough that a variety of causes causes.Its antitussive effect equates with codeine or is strong slightly.It can suppress the oblongata coughing centre and play antitussive effect, but does not have analgesic effect, a little less than the addiction.Oral back onset half an hour, effect continues 6 hours, at liver metabolism, is discharged by kidney with original shape or metabolite form then.Be widely used in the cough that flu or other reason cause.The cough medicine that this medicine is thought to replace codeine by World Health Organization (WHO) has obtained increasingly extensive application.The each oral 15～30mg of dextromethorphan hydrobromide adult, 3～4 times on the one.
The compound preparation that contains arbidol HCl provided by the present invention, its active component comprises arbidol HCl, ibuprofen, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, wherein Abiduoer is a kind of component necessary in the pharmaceutical composition, Abiduoer can with a kind of, the two or three active component combination in any in ibuprofen, pseudoephedrine hydrochloride, the dextromethorphan hydrobromide.Its dosage form can be various peroral dosage forms such as tablet, capsule, granule, dry suspension.
The compound preparation that contains Abiduoer of the present invention contains arbidol HCl 25～40% by weight percentage, ibuprofen 60～75%.
The compound preparation that contains Abiduoer of the present invention contains arbidol HCl 23%～38% by weight percentage, ibuprofen 55～72%, pseudoephedrine hydrochloride 2～10%.
The compound preparation that contains Abiduoer of the present invention contains arbidol HCl 23%～38% by weight percentage, ibuprofen 55～72%, dextromethorphan hydrobromide 2～10%.
The compound preparation that contains Abiduoer of the present invention contains arbidol HCl 20～36% by weight percentage, ibuprofen 53～72%, pseudoephedrine hydrochloride 2～8.5%, dextromethorphan hydrobromide 2～8.5%.
Active component in the above-mentioned various compound preparation can adopt conventional preparation technology, add the acceptable oral preparation pharmaceutic adjuvant, make oral dosage form, peroral dosage forms such as tablet, capsule, granule, dry suspension, and can adjust various active component consumption, take for the patient of all ages and classes.
Oral solid formulations such as the tablet among the present invention, capsule, granule, dry suspension can adopt the preparation method of these dosage form routines to be prepared, and can contain adjunct ingredients such as above-mentioned active component and excipient, disintegrating agent, binding agent, suspending agent, lubricant, coating materials, sweeting agent, flavouring agent in its prescription.
Because the eutectic phenomenon can take place after mixing with ibuprofen in arbidol HCl, thus in preparation process, should adopt the method for granulating respectively to avoid making these two kinds of active component directly to contact,
Arbidol HCl and part excipient, disintegrating agent are put in the mixer-granulator behind the mix homogeneously, added binding agent and make granule I; Other active component and remainder excipient, disintegrating agent behind the mix homogeneously, are added binding agent and make granule II in mixer-granulator; Dried two kinds of granules can directly be incapsulated behind the mix homogeneously in mixer.
Arbidol HCl and part excipient, disintegrating agent are put in the mixer-granulator behind the mix homogeneously, added binding agent and make granule I; Other active component and part excipient, disintegrating agent behind the mix homogeneously, are added binding agent and make granule II in mixer-granulator; Dried two kinds of granules are put in the mixer, be can be made into tablet with the even back of mix lubricant tabletting.This tablet coating material also seldom available or that do not influence the tablet stripping carries out coating to guarantee tablet good surface appearance and stability.
Arbidol HCl and part excipient, sweeting agent are put in the mixer-granulator behind the mix homogeneously, added binding agent and make granule I; Other active component and part excipient, sweeting agent behind the mix homogeneously, are added binding agent and make granule II in mixer-granulator; Dried two kinds of granules are put in the mixer, be can be made into granule with dividing behind the flavouring agent mix homogeneously in the pouch of packing into.
Arbidol HCl and part excipient, sweeting agent, suspending agent are put in the mixer-granulator behind the mix homogeneously, added binding agent and make granule I; Other active component and part excipient, sweeting agent, suspending agent behind the mix homogeneously, are added binding agent and make granule II in mixer-granulator; Dried two kinds of granules are put in the mixer, be can be made into dry suspension with dividing behind the flavouring agent mix homogeneously in the pouch of packing into.
Excipient is selected from: lactose, sucrose, glucose, mannitol, sorbitol, erythrose, starch, pregelatinized Starch, microcrystalline Cellulose etc.;
Disintegrating agent is selected from: carboxymethyl starch sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose etc.;
Binding agent is selected from: starch, sucrose, methylcellulose, hydroxypropyl methylcellulose, polyvidone etc.;
Suspending agent is selected from: sodium carboxymethyl cellulose, polyvidone, sodium alginate etc.;
Opadry), acrylic resin IV number etc. coating material is selected from: hydroxypropyl methylcellulose (coating powder trade name:;
Sweeting agent is selected from: aspartame, cyclamate, Sucralose etc.;
Flavouring agent is selected from: various fruity powder essence.
Compound preparation of the present invention can be taken with reference to following consumption:
The adult: oral, 3 times on the one, the amount of corresponding active component is arbidol HCl 100～200mg in the preparation of at every turn taking, ibuprofen 200～400mg, pseudoephedrine hydrochloride 15～30mg, dextromethorphan hydrobromide 15～30mg.
The child: oral, 3 times on the one, the amount of corresponding active component is arbidol HCl 50～100mg in the preparation of at every turn taking, ibuprofen 100～200mg, pseudoephedrine hydrochloride 5～15mg, dextromethorphan hydrobromide 5～15mg.
The compound preparation that contains Abiduoer of the present invention, various active component concertednesses are good, the good result that produces, can pass through following effect experiment explanation, prescription I, II, III, IV are respectively Abiduoer 100mg and ibuprofen 150mg, Abiduoer 100mg, ibuprofen 150mg and pseudoephedrine hydrochloride 15mg, Abiduoer 100mg, ibuprofen 150mg and dextromethorphan hydrobromide 7.5mg, Abiduoer 100mg, ibuprofen 150mg, pseudoephedrine hydrochloride 15mg and dextromethorphan hydrobromide 7.5mg.
One, to the effect of mice influenza virus property pneumonia
Mice is divided into 10 groups at random by body weight: the virus control group of not administration, prescription I, II, III, IV small dose group and heavy dose of group (25mg/kg, 50mg/kg is in Abiduoer), Abiduoer matched group (25mg/kg), 10 every group.1d begins successive administration 5d before infecting.Infect the same day, mice is slightly anaesthetized through ether, carry out the collunarium infection with the influenza virus Mus lung adapted strain FM1 of 15LD50.Mice is weighed earlier afterwards to dissect get lung and claim lung heavily in infecting back 4d.Calculate lung exponential quantity (100 * lung weight/body weight), carry out statistical disposition, and obtain the suppression ratio of medicine pneumonia.
The result shows that prescription I, II, III, IV small dose group and heavy dose of group have than obvious suppression effect (comparing P＜0.01 with the virus control group) mice stream viral pneumonia, and heavy dose of group suppression ratio reaches 37.35%.Heavy dose of group suppression ratio reaches more than 26.48% suitable with positive controls (suppression ratio reaches 25.96%), adds pseudoephedrine hydrochloride, dextromethorphan hydrobromide and ibuprofen among prescription II, III, the IV drug effect to Abiduoer is not made significant difference.
Two, refrigeration function
Get 60 of health large ear rabbits, body weight 1.5kg～2.5kg, be divided into 10 groups at random, every group 6, male and female half and half, the virus control group of not administration, prescription I, II, III, IV small dose group and heavy dose of group (25mg/kg, 50mg/kg is in Abiduoer), positive controls (ibuprofen 40mg/kg).Be gastric infusion, every day 1 time, 3d continuously.0.5h injects endotoxin (colibacillus O111 B4) 2.4ml/kg (5Eu/ml) from auricular vein after the last administration, before this vaccine of injection and after 1,3,4,5,6h surveys body temperature (with Omron, Dalian clinical thermometer MC-3B computer numeral formula body temperature instrumentation anus temperature) 1 time, continuous measurement 6h.Record is respectively organized body temperature and is changed.
Prescription I, II, III, IV be to heating rabbit children antipyretic effect preferably, wherein each heavy dose of group its imitate soon and strong, in 4 hours, can body temperature be reduced to normally; Small dose group and positive control are suitable, can reduce to body temperature normally in 6 hours, and adding pseudoephedrine hydrochloride and dextromethorphan hydrobromide do not make significant difference to the refrigeration function of ibuprofen among prompting prescription II, III, the IV.
Three, analgesic activity
The mice hot plate method screens qualified ♀ mice (pain response latency at 30s with interior person) with hot plate reaction and is divided into 10 groups at random, every group 10, be blank group, positive controls (ibuprofen 40mg/kg), prescription I, II, III, IV small dose group and heavy dose of group (25mg/kg, 50mg/kg is in Abiduoer).The ig administration, measure respectively before the mice administration with administration after 1,2,4, pain reaction (hot plate method) incubation period of 6h.Place on the metallic plate of DS-501 type thermostatic water-circulator bath (production of Chongqing experimental facilities factory) 55 ℃ ± 0.5 ℃ of bath temperature respectively.From dropping into hot plate, lick the pain reaction time (incubation period) of metapedes as threshold of pain index with stopwatch record mice with mice to the time that metapedes occurs licking (s).Pain threshold surpasses 60s, by 60s.
Glacial acetic acid inducing mouse writhing response is got 100 of mices,
The ♀ dual-purpose is divided into 10 groups at random, i.e. blank group, positive controls (ibuprofen 40mg/kg), prescription I, II, III, IV small dose group and heavy dose of group (25mg/kg, 50mg/kg is in Abiduoer).Behind the ig administration 1h, every Mus ip 0.7% glacial acetic acid 0.1mg/10g observes mouse writhing in the 15min (abdominal part indent, trunk and back leg extension, hips up) frequency immediately.The adding of pseudoephedrine hydrochloride and dextromethorphan hydrobromide does not make significant difference to the analgesic activity of ibuprofen among formula I I, III, the IV.
The result shows that prescription I, II, the heavy dose of group of III, IV can obviously improve the pain threshold that mice heat is brought out pain reaction, and with matched group comparing difference significance (P＜0.01), and this effect is held time longer.Suitable when low dose of to the influence and the positive controls of hot plate reaction.
Can cause the more persistent pain stimulation of mice after result's experiment that glacial acetic acid brings out mouse writhing reaction shows ig acetic acid, writhing response appears in mice.Prescription I, II, III, IV small dose group and heavy dose of group all can reduce the writhing response number of times of mice, and suppression ratio is respectively 47.5% and 54.7%, turns round the body number of times in the 15min and is starkly lower than blank group (P＜0.01).The adding of pseudoephedrine hydrochloride and dextromethorphan hydrobromide does not make significant difference to the analgesic activity of ibuprofen among prescription II, III, the IV.
Four, to the influence of Cavia porcellus nasal mucosa sensitization
Choose 48 of healthy guinea pigs, be divided into 6 groups at random, 8 every group by the body weight equilibrium.The blank group, prescription II, IV small dose group and heavy dose of group (40mg/kg, 80mg/kg is in Abiduoer), pseudoephedrine hydrochloride positive controls (6mg/kg), ig administration, 3d continuously, 30min after the last administration, Maxamine solution with 2% splashes into nasal cavity (bilateral) with the every nostril 50 μ l of sample injector, waits nose or sneeze reaction back observation 10min to occur grabbing, and nose and sneeze number of times grabbed in record.The results are shown in Table 1.
Table 2 prescription II, IV to histamine cause irritant reaction influence (x ± s, n=6)
| Group | Dosage (mg/kg) | Sneeze (inferior/10min) | Grab nose (inferior/10min) |
| Normal saline | ????- | ????51.0±8.3 | ????59.6±16.8 |
| Prescription II | ????40 | ????37.8±7.8 ** | ????45.6±9.1 ** |
| ????80 | ????35.4±5.4 ** | ????42.7±10.4 ** | |
| Prescription IV | ????40 | ????38.5±12 ** | ????46.5±12 ** |
| ????80 | ????34.0±9.1 ** | ????41.9±10.5 ** | |
| Positive control | ????6 | ????38.9±9.2 ** | ????46.7±8.2 ** |
As known from Table 1: prescription II, IV can alleviate the irritative response that histamine causes Cavia porcellus, and with the sneeze of matched group comparison Cavia porcellus with grab the nose phenomenon and obviously alleviate, its effect is similar to pseudoephedrine hydrochloride.
Five, antitussive effect
White mice ammonia draw the method for coughing get body weight (60 of 20 ± 2g) mices,
The ♀ dual-purpose carries out preliminary election, gets qualified mice, be divided into 6 groups at random, blank group, prescription III, IV small dose group and heavy dose of group (25mg/kg, 50mg/kg is in Abiduoer), dextromethorphan hydrobromide positive controls (3mg/kg) group, ig administration, every day 1 time, gastric infusion is 3 days continuously, 1h after the last administration, mice is put in the glass bell jar, carry out promptly taking out after ammonia spraying stimulates 20s, observe mice and draw the cough number of times of coughing in incubation period and the 2min, the results are shown in Table 2.
Table 3 termitarium draws the influence the coughed (n=10 of x ± S) to mice ammonia
| Group | Dosage (mg/kg) | Cough latent period (s) | Cough number of times/2min |
| Normal saline | ???- | ????33.23±16.06 | ????18.09±8.69 |
| Formula I II | ???40 | ????53.10±25.03 ** | ????11.10±7.40 ** |
| ???80 | ????61.30±23.91 ** | ????8.95±7.06 ** | |
| Formula I V | ???40 | ????50.00±22.41 ** | ????11.33±5.65 ** |
| ???80 | ????62.50±25.41 ** | ????9.10±6.21 ** | |
| Positive control | ???3 | ????51.00±21.07 ** | ????11.78±5.50 ** |
Annotate:
*Compare P＜0.01 with the normal saline group
The result shows, prescription III, IV small dose group and heavy dose of group can obviously prolong mice and draw and cough incubation period (P＜0.01), prescription III, IV small dose group and heavy dose of group all can reduce the cough number of times (P＜0.01) in the 2min, and the effect of prescription III, IV small dose group is all suitable in positive controls.Prompting is under this experiment condition, and prescription III, IV small dose group and heavy dose of group all have obvious antitussive action.
The specific embodiment
The compound preparation that contains Abiduoer of the present invention, its preferred prescription are respectively to contain Abiduoer 100mg and ibuprofen 150mg; Contain Abiduoer 100mg, ibuprofen 150mg and pseudoephedrine hydrochloride 15mg; Contain Abiduoer 100mg, ibuprofen 150mg and dextromethorphan hydrobromide 7.5mg; Contain Abiduoer 100mg, ibuprofen 150mg, pseudoephedrine hydrochloride 15mg and dextromethorphan hydrobromide 7.5mg.
Embodiment one: arbidol HCl/brufen pellet (1g/ bag)
(1) prescription:
Granule I:
Arbidol HCl 50mg
Mannitol 435mg
Sucralose 0.7mg
Yellow 6
#1mg
2% hydroxypropyl emthylcellulose, 60% alcoholic solution is an amount of
Granule II:
Ibuprofen 100mg
Mannitol 389mg
Yellow 6
#1mg
2% hydroxypropyl emthylcellulose, 60% alcoholic solution is an amount of
Extra Section:
Fructus Citri sinensis powdered flavor 20mg
(2) operating procedure:
1. prepare binding agent: with yellow 6
#Be dissolved in after the low amounts of water and 2% hydroxypropyl emthylcellulose, 60% alcoholic solution mix homogeneously;
2. make granule I: will pulverize the same mannitol of arbidol HCl, Sucralose mix homogeneously in mixer-granulator of 100 mesh sieves, and add suitable amount of adhesive and granulate 50～55 ℃ of dryings;
3. make granule II: the ibuprofen that will cross 100 mesh sieves adds suitable amount of adhesive and granulates 50～55 ℃ of dryings with mannitol mix homogeneously in mixer-granulator.
4. granule I is mixed with granule II, add Fructus Citri sinensis powdered flavor mix homogeneously, be sub-packed in the aluminium foil bag by doing particle weight.
Embodiment two: arbidol HCl/Genpril (485mg/ sheet)
(1) prescription:
Granule I:
Arbidol HCl 100mg
Starch 30mg
Microcrystalline Cellulose 60mg
Crospolyvinylpyrrolidone 2mg
10% polyvidone, 50% alcoholic solution is an amount of
Granule II:
Ibuprofen 150mg
Starch 40mg
Microcrystalline Cellulose 80mg
Crospolyvinylpyrrolidone 3mg
10% polyvidone, 50% alcoholic solution is an amount of
Extra Section:
Magnesium stearate 5mg
Coating material:
Opadry 15mg
(2) operating procedure:
1. make granule I: will pulverize the same starch of arbidol HCl, microcrystalline Cellulose, crospolyvinylpyrrolidone mix homogeneously in mixer-granulator of 100 mesh sieves, and add an amount of 10% polyvidone, 50% alcoholic solution and granulate 50～55 ℃ of dryings;
2. make granule II: will cross ibuprofen and starch and microcrystalline Cellulose mix homogeneously in mixer-granulator of 100 mesh sieves, and add an amount of 10% polyvidone, 50% alcoholic solution and granulate 50～55 ℃ of dryings.
3. granule I is mixed with granule II, add magnesium stearate mix homogeneously, tabletting by doing particle weight.
4. label is put and coated the stomach dissolution type film-coat in the coating pan
Embodiment three: arbidol HCl/ibuprofen/pseudoephedrine hydrochloride sheet (500mg/ sheet)
(1) prescription:
Granule I:
Arbidol HCl 100mg
Starch 30mg
Microcrystalline Cellulose 60mg
Crospolyvinylpyrrolidone 2mg
10% polyvidone, 50% alcoholic solution is an amount of
Granule II:
Ibuprofen 150mg
Pseudoephedrine hydrochloride 15mg
Starch 40mg
Microcrystalline Cellulose 80mg
Crospolyvinylpyrrolidone 3mg
10% polyvidone, 50% alcoholic solution is an amount of
Extra Section:
Magnesium stearate 5mg
Coating material:
Opadry 15mg
(2) operating procedure:
1. make granule I: will pulverize the same starch of arbidol HCl, microcrystalline Cellulose, crospolyvinylpyrrolidone mix homogeneously in mixer-granulator of 100 mesh sieves, and add an amount of 10% polyvidone, 50% alcoholic solution and granulate 50～55 ℃ of dryings;
2. make granule II: will cross the pseudoephedrine hydrochloride of 100 mesh sieves and starch and adopt the equivalent method mixing that progressively increases; again with ibuprofen and the microcrystalline Cellulose mix homogeneously in mixer-granulator of crossing 100 mesh sieves; add an amount of 10% polyvidone, 50% alcoholic solution and granulate 50～55 ℃ of dryings.
3. granule I is mixed with granule II, add magnesium stearate mix homogeneously, tabletting by doing particle weight.
4. label is put and coated the stomach dissolution type film-coat in the coating pan.
Embodiment four: arbidol HCl/ibuprofen/pseudoephedrine hydrochloride sheet (560mg/ sheet)
(1) prescription:
Granule I:
Arbidol HCl 100mg
Starch 30mg
Microcrystalline Cellulose 60mg
Crospolyvinylpyrrolidone 2mg
10% polyvidone, 50% alcoholic solution is an amount of
Granule II:
Ibuprofen 200mg
Pseudoephedrine hydrochloride 15mg
Starch 50mg
Microcrystalline Cellulose 90mg
Crospolyvinylpyrrolidone 3mg
10% polyvidone, 50% alcoholic solution is an amount of
Extra Section:
Magnesium stearate 5.6mg
Coating material:
Opadry 16mg
(2) operating procedure:
1. make granule I: will pulverize the same starch of arbidol HCl, microcrystalline Cellulose, crospolyvinylpyrrolidone mix homogeneously in mixer-granulator of 100 mesh sieves, and add an amount of 10% polyvidone, 50% alcoholic solution and granulate 50～55 ℃ of dryings;
2. make granule II: will cross the pseudoephedrine hydrochloride of 100 mesh sieves and starch and adopt the equivalent method mixing that progressively increases; again with ibuprofen and the microcrystalline Cellulose mix homogeneously in mixer-granulator of crossing 100 mesh sieves; add an amount of 10% polyvidone, 50% alcoholic solution and granulate 50～55 ℃ of dryings.
3. granule I is mixed with granule II, add magnesium stearate mix homogeneously, tabletting by doing particle weight.
4. label is put and coated the stomach dissolution type film-coat in the coating pan.
Embodiment five: arbidol HCl/ibuprofen/dextromethorphan hydrobromide capsule (450mg/ grain)
(1) prescription:
Granule I:
Arbidol HCl 100mg
Lactose 30mg
Pregelatinized Starch 30mg
Carboxymethyl starch sodium 3mg
10% starch slurry is an amount of
Granule II:
Ibuprofen 200mg
Dextromethorphan hydrobromide 15mg
Lactose 65mg
Carboxymethyl starch is received 5mg
10% starch slurry is an amount of
(2) operating procedure:
1. make granule I: will pulverize the same lactose of arbidol HCl, pregelatinized Starch, carboxymethyl starch sodium mix homogeneously in mixer-granulator of 100 mesh sieves, and add an amount of 10% starch slurry and granulate 50～55 ℃ of dryings;
2. make granule II: will cross the dextromethorphan hydrobromide of 100 mesh sieves and lactose and adopt the equivalent method mixing that progressively increases, and, add an amount of 10% starch slurry and granulate 50～55 ℃ of dryings again with ibuprofen and the lactose mix homogeneously in mixer-granulator of crossing 100 mesh sieves.
3. with granule I with granule II mix homogeneously, incapsulate.
Embodiment six: arbidol HCl/ibuprofen/dextromethorphan hydrobromide capsule (225mg/ grain)
(1) prescription:
Granule I:
Arbidol HCl 50mg
Lactose 10mg
Pregelatinized Starch 15mg
Carboxymethyl starch sodium 1mg
10% starch slurry is an amount of
Granule II:
Ibuprofen 100mg
Dextromethorphan hydrobromide 5mg
Lactose 40mg
Carboxymethyl starch sodium 3mg
10% starch slurry is an amount of
(2) operating procedure:
1. make granule I: will pulverize the same lactose of arbidol HCl, pregelatinized Starch, carboxymethyl starch sodium mix homogeneously in mixer-granulator of 100 mesh sieves, and add an amount of 10% starch slurry and granulate 50～55 ℃ of dryings;
2. make granule II: will cross the dextromethorphan hydrobromide of 100 mesh sieves and lactose and adopt the equivalent method mixing that progressively increases, and, add an amount of 10% starch slurry and granulate 50～55 ℃ of dryings again with ibuprofen and the lactose mix homogeneously in mixer-granulator of crossing 100 mesh sieves.
3. with granule I with granule II mix homogeneously, incapsulate.
Embodiment seven: arbidol HCl/ibuprofen/pseudoephedrine hydrochloride/dextromethorphan hydrobromide dry suspension (2g/ bag)
(1) prescription:
Granule I:
Arbidol HCl 100mg
Cane sugar powder 450mg
Mannitol 220mg
Sodium carboxymethyl cellulose 20mg
Aspartame 1mg
10% polyvidone, 50% ethanol liquid is an amount of
Granule II:
Ibuprofen 200mg
Pseudoephedrine hydrochloride 30mg
Dextromethorphan hydrobromide 15mg
Cane sugar powder 300mg
Mannitol 600mg
Sodium carboxymethyl cellulose 20mg
Aspartame 1mg
10% polyvidone, 50% ethanol liquid is an amount of
Extra Section:
Fructus Fragariae Ananssae powdered flavor 40mg
(2) operating procedure:
1. make granule I: will pulverize the same cane sugar powder of arbidol HCl, mannitol, sodium carboxymethyl cellulose mix homogeneously in mixer-granulator of 120 mesh sieves, and add an amount of 10% polyvidone, 50% ethanol liquid and granulate 50～55 ℃ of dryings;
2. make granule II: will cross 120 mesh sieves pseudoephedrine hydrochloride, dextromethorphan hydrobromide, adopt the equivalent method mixing that progressively increases with sodium carboxymethyl cellulose, cane sugar powder; again with ibuprofen and the mannitol mix homogeneously in mixer-granulator of crossing 120 mesh sieves; add an amount of 10% polyvidone, 50% ethanol liquid and granulate 50～55 ℃ of dryings.
3. granule I is mixed with granule II, add Fructus Fragariae Ananssae powdered flavor mix homogeneously, divide in the aluminium foil bag of packing into.
Embodiment eight: arbidol HCl/ibuprofen/pseudoephedrine hydrochloride/dextromethorphan hydrobromide dry suspension (3g/ bag)
(1) prescription:
Granule I:
Arbidol HCl 200mg
Cane sugar powder 245mg
Mannitol 490mg
Sodium carboxymethyl cellulose 30mg
Aspartame 1.5mg
10% polyvidone, 50% ethanol liquid is an amount of
Granule II:
Ibuprofen 400mg
Pseudoephedrine hydrochloride 30mg
Dextromethorphan hydrobromide 30mg
Cane sugar powder 490mg
Mannitol 980mg
Sodium carboxymethyl cellulose 30mg
Aspartame 1.5mg
10% polyvidone, 50% ethanol liquid is an amount of
Extra Section:
Fructus Fragariae Ananssae powdered flavor 60mg
(2) operating procedure:
1. make granule I: will pulverize the same cane sugar powder of arbidol HCl, mannitol, sodium carboxymethyl cellulose mix homogeneously in mixer-granulator of 120 mesh sieves, and add an amount of 10% polyvidone, 50% ethanol liquid and granulate 50～55 ℃ of dryings;
2. make granule II: will cross 120 mesh sieves pseudoephedrine hydrochloride, dextromethorphan hydrobromide, adopt the equivalent method mixing that progressively increases with sodium carboxymethyl cellulose, cane sugar powder; again with ibuprofen and the mannitol mix homogeneously in mixer-granulator of crossing 120 mesh sieves; add an amount of 10% polyvidone, 50% ethanol liquid and granulate 50～55 ℃ of dryings.
3. granule I is mixed with granule II, add Fructus Fragariae Ananssae powdered flavor mix homogeneously, divide in the aluminium foil bag of packing into.
Claims (7)
1, a kind of influenza compound preparation that contains arbidol HCl, basically by in Abiduoer and ibuprofen, pseudoephedrine hydrochloride, the dextromethorphan hydrobromide a kind of, two or three form.
2, according to the described influenza compound preparation that contains arbidol HCl of claim 1, it is characterized in that containing arbidol HCl 25～40%, ibuprofen 60～75%.
3, according to the described influenza compound preparation that contains arbidol HCl of claim 1, it is characterized in that containing arbidol HCl 23%～38%, ibuprofen 55～72%, pseudoephedrine hydrochloride 2～10%.
4, according to the described influenza compound preparation that contains arbidol HCl of claim 1, it is characterized in that containing arbidol HCl 23%～38%, ibuprofen 55～72%, dextromethorphan hydrobromide 2～10%.
5, according to the described influenza compound preparation that contains arbidol HCl of claim 1, it is characterized in that containing arbidol HCl 20～36%, ibuprofen 53～72%, pseudoephedrine hydrochloride 2～8.5%, dextromethorphan hydrobromide 2～8.5%.
6, according to claim 2,3, the 4 or 5 described influenza compound preparations that contain arbidol HCl, it is characterized in that also adding the acceptable oral preparation pharmaceutic adjuvant is arranged, make oral dosage form.
7, according to the described influenza compound preparation that contains arbidol HCl of claim 6, it is characterized in that tablet, capsule, granule or dry suspension.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410037164 CN1572298B (en) | 2003-06-06 | 2004-06-05 | Arbidol containing compound preparation |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN03137163 | 2003-06-06 | ||
| CN03137163.9 | 2003-06-06 | ||
| CN 200410037164 CN1572298B (en) | 2003-06-06 | 2004-06-05 | Arbidol containing compound preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1572298A true CN1572298A (en) | 2005-02-02 |
| CN1572298B CN1572298B (en) | 2011-11-02 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410037164 Expired - Fee Related CN1572298B (en) | 2003-06-06 | 2004-06-05 | Arbidol containing compound preparation |
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| Country | Link |
|---|---|
| CN (1) | CN1572298B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100428935C (en) * | 2006-06-26 | 2008-10-29 | 四川百利药业有限责任公司 | Abiduoer granular formulation |
| CN102000030A (en) * | 2010-11-08 | 2011-04-06 | 东北制药（沈阳）科技发展有限公司 | Arbidol dry suspension and preparation method thereof |
| CN112933061A (en) * | 2021-02-22 | 2021-06-11 | 石家庄四药有限公司 | Arbidol hydrochloride capsule and preparation method thereof |
-
2004
- 2004-06-05 CN CN 200410037164 patent/CN1572298B/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100428935C (en) * | 2006-06-26 | 2008-10-29 | 四川百利药业有限责任公司 | Abiduoer granular formulation |
| CN102000030A (en) * | 2010-11-08 | 2011-04-06 | 东北制药（沈阳）科技发展有限公司 | Arbidol dry suspension and preparation method thereof |
| CN102000030B (en) * | 2010-11-08 | 2012-11-21 | 东北制药（沈阳）科技发展有限公司 | Arbidol dry suspension and preparation method thereof |
| CN112933061A (en) * | 2021-02-22 | 2021-06-11 | 石家庄四药有限公司 | Arbidol hydrochloride capsule and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1572298B (en) | 2011-11-02 |
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