CN1762377A - Medicinal composition containing zidovudine, valproic acid or its salt - Google Patents
Medicinal composition containing zidovudine, valproic acid or its salt Download PDFInfo
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- CN1762377A CN1762377A CN 200510086716 CN200510086716A CN1762377A CN 1762377 A CN1762377 A CN 1762377A CN 200510086716 CN200510086716 CN 200510086716 CN 200510086716 A CN200510086716 A CN 200510086716A CN 1762377 A CN1762377 A CN 1762377A
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Abstract
The invention relates to a therapeutic combination containing Azidothimidine and dipropylacetic acid or its salts, wherein the formulation of the medicinal composition comprises (by weight percentage) Azidothimidine 0.1-95%, dipropylacetic acid or its salts 1.0-95%, and medicinal auxiliary material 4-98.9%. Each unit of the dosage preferably comprises Azidothimidine 10-600mg, dipropylacetic acid or its salts 50-500mg, and pharmaceutically acceptable auxiliary materials amounting to 15-40% of the total weight of the unit dosage. The combination can be used for the treatment of human immunodeficiency virus (HIV) infection.
Description
Technical field:
The present invention relates to a kind of Pharmaceutical composition that contains active component zidovudine and valproic acid or its salt that is used for the treatment of the acquired immunodeficiency syndrome that HIV (human immunodeficiency virus) infection causes.
Background technology:
HIV (human immunodeficiency virus) (human immunodeficiency virus, HIV) infect acquired immunodeficiency syndrome (the aquired immunodeficiency syndrome that causes, AIDS) be commonly called as acquired immune deficiency syndrome (AIDS), just worldwide be widely current at present, become great public health and social problem highly visible.It is generally acknowledged that now HIV is the relevant syndrome with AIDS of AIDS (AIDS-related complex, pathogenic factor ARC).Not only HIV is the main cause of AIDS, and the HIV infection can be passed in time usually and be caused immunodeficiency extremely separately, and patient is caused death.Because the public's attention, HIV also becomes and studies one of deep virus in history.Although scientist has done effort, still this fatal disease can't effectively even there be satisfied Therapeutic Method.
Domestic HIV (human immunodeficiency virus) infection number rises year by year, and at present number every year of China's aids infection, as not taking active and effective control, by 2010, China's patients infected hiv will be above 1,000 ten thousand people with 30% speed increase.At present, the medicine of world's listing treatment HIV virus has twenties kinds, domestic imitation patent expired and not at 5 kinds of essential drugses of the row of administrative protection, filled up the blank of state's internal therapy AIDS-treating medicine.But the simple and not high therapeutic effect that greatly reduces medicine of drug quality of listing dosage form.
(highly-active antiretroviral therapy HAART), is acknowledged as a milestone on the treating AIDS to " highly active antiretroviral therapy " that scientist Chinese descendant in America He Dayi proposes.The therapeutic modality of this drug combination generically is called " HAART " again, it is by suppressing virus replication, recovering immune function of human body, improved the therapeutic effect of acquired immune deficiency syndrome (AIDS) significantly, reduced mortality rate, thereby develop into the conventional treatments of acquired immune deficiency syndrome (AIDS) gradually, and worldwide (especially in American-European countries) is widely used.However, nearly 10 years clinical practice shows, HAART and unlike what people expected can thoroughly be removed HIV (human immunodeficiency virus) in the infected's body, " cocktail " of this both expensive be thorough treatment of AIDS also at present, and needs of patients is accepted lifelong treatment.Causing an important reasons of this situation to be exactly-some virus just is in " resting state " after entering the immunocyte of human body.Thisly stop to duplicate, do not have active virus " to hide " in cell, antiviral drugs just can't be killed them, in case and patient stops using antiviral drugs, these viruses can " be revived " again again, enter replication status, cause new infection, " HAART " also has some shortcomings of can not ignore except costing an arm and a leg.The one, side effect, digestive tract reaction often appears in this therapy, as nausea,vomiting,diarrhea etc.; Also suppress the bone marrow hematogenesis function, cause serious anemia; In addition, also can cause lipodystrophy, as buffalo hump, spider-man and central obesity etc.; The 2nd, drug resistance, medication is after 3,4 months, and effect is just bad, must select medicine again.
" lancet " on August 13rd, 2005
[1]In the research report of magazine, David's mug(unit of measure) doctor Li Si of North Carolina, US university leader's research group is used for a kind of antuepileptic-valproic acid (valproic acid) commonly used the treatment of acquired immune deficiency syndrome (AIDS).This method can be removed the HIV (human immunodeficiency virus) that hides in human body cell, escapes the medicine attack.Valproic acid or its salt have the effect of synthesizing and block its degraded that promotion reaches central nervous system's inhibitory transmitter γ-An Jidingsuan on every side; can inhibition of histone acetylase I; thereby stop HIV to hide for a long time in the CD4+ of human body cell with state static, that hide; the effect of valproic acid is the virus of " waking up " resting state, and just can be killed by effective antiviral drugs behind the activated viral.The advantage of valproic acid or its salt is that it is a kind of by clear cognitive medicine, is used to the long-term treatment of epilepsy, migraine and emotional maladjustment, and most of people have good toleration to it, total fatality rate is 1: 51,300 (Bryant AE, the neurological 1986,40:465-469).
Zidovudine is one of common drug in the anti-AIDS HAART, belongs to the thymidine nucleoside analog, brings into play antiviral activity by the cell kinase phosphorylation, can suppress HIV virus duplicating in human body cell.
Summary of the invention
An object of the present invention is to provide and a kind ofly can activate the effective Pharmaceutical composition that hides the HIV that in cell, is in resting state, in the hope of removing the HIV virus that is in state of activation and resting state in the body simultaneously.
Another object of the present invention is to provide a kind of new Pharmaceutical composition that obtains being characterized as pharmaceutically acceptable homogeneous mixture that active constituent is mixed for treatment AIDS.
The 3rd purpose of the present invention is to reduce the untoward reaction that three or tetrad medication commonly used are at present brought, and reduces the expense of treatment AIDS, so that the therapeutic scheme of AIDS can be popularized in China and other developing countries.
The present invention relates to comprise the therapeutics combination of zidovudine and valproic acid or its salt, the formula range of its Pharmaceutical composition (all by weight percentage calculate): zidovudine is 0.1～95%, valproic acid or its salt or valpromide are 1.0%～95%, pharmaceutic adjuvant 4～98.9%.Be used for the treatment of HIV (human immunodeficiency virus) (HIV) and infect, and be used in particular for treating AIDS or the relevant syndrome of AIDS (ARC).In the per unit dosage form, preferably contain the zidovudine of 10～600mg and valproic acid or its salt or the valpromide of 50～500mg, and the acceptable accessories that accounts for unit dosage forms gross weight 20%～40%.
Zidovudine, its chemistry 3 '-azido-3 ' by name-deoxyribosylthymine (Zidovudine, AZT), structural formula is as follows:
Valproic acid, chemistry 2-Propylpentanoic by name is a kind of acetylation of histone enzyme inhibitor, its structural formula is as follows:
Term " evenly " refers in this article that these active constituents are dispersed in basically and contains their whole and make in the tablet that the uniformity of active constituent can detect by the medicine uniformity and determine in tablet.
Term " safety and effective dose " refers to the performance preparation function sought by research worker or clinician in this article and the patient's of this preparation the amount of preparation of tissue is accepted in not serious infringement.
Valproic acid and salt thereof related among the present invention comprise pharmaceutically acceptable valproic acid, sodium valproate, magnesium valproate and valproic acid calcium etc., comprise that also valproic acid is at the pharmaceutically acceptable derivates valpromide.
The preparation supplementary material:
The lubricant of disintegrating agent, safety and the effective dose of binding agent, safety and the effective dose of diluent, safety and the effective dose of the optionally safe in utilization and effective dose of Pharmaceutical composition of the present invention and other pharmaceutically acceptable coloring agent and correctivess of safety and effective dose
The Pharmaceutical composition that contains zidovudine, valproic acid or its salt and pharmaceutic adjuvant is based on 100% of gross weight, contain: 1. 0.1～95% zidovudine, 2. 1～95% valproic acid or its salt, 3. 0～35% diluent, 4. 0～20% binding agent, 5. 6. 0～10% lubricant and 7. 0～10% other pharmaceutically acceptable fluidizer, coloring agent and/or correctives of 0～30% disintegrating agent.
Diluent used among the present invention is in order to increase the weight and volume of preparation, can be that one or more can provide the volumes of formulation of acquisition expectation or the chemical compound of weight, comprise in lactose, sucrose, mannitol, sorbitol, starch, pregelatinized Starch, cellulose, processing agar, gelatin or the dextrin one or more.
Binding agent among the present invention is to be used for granulating and the adherent excipient of tabletting, comprises the water of one or more adjuvants in water, ethanol, tween 80, polyvinylpyrrolidone (PVP), hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium alginate, aluminium-magnesium silicate, arabic gum or the Polyethylene Glycol or the solution of alcohol.
Disintegrating agent among the present invention is disintegrate when being used to promote the preparation of preparation of compositions to contact with aqueous medium, comprises in carboxymethyl starch sodium (CMS-Na), crosslinked carboxymethyl fecula sodium (cCMS-Na), low-substituted hydroxypropyl cellulose (LHPC), crospolyvinylpyrrolidone (PVPP), AmberliteIRP-88, sodium carboxymethyl cellulose (CMC-Na), cross-linking sodium carboxymethyl cellulose (cCMC-Na), carboxymethylcellulose calcium or the microcrystalline Cellulose (MCC) one or more.
Lubricant among the present invention is in order to feed in raw material smoothly and slice, comprises in magnesium stearate, calcium stearate, stearic acid, Polyethylene Glycol, silicon dioxide, micropowder silica gel, Pulvis Talci, aluminium hydroxide or the Stepanol MG one or more.
Pharmaceutically acceptable coloring agent of among the present invention other and correctives comprise red, red scarlet, the light blue of coloring agent lemon yellow, sunset yellow, carmine, amaranth, temptation, indigo, light green, egg yolk and medicinal color lake and correctives A Siba is sweet, in glycyrrhizin, stevioside, saccharin sodium or the medicinal essence one or more.
The present invention preferably exists with the form of the pharmaceutical preparation that is suitable for oral administration.These preparations can be discontinuous easily the unit exist, as tablet, scrotiform tablet, capsule or be suitable for any other oral and compatible preparation, wherein contain the active constituent of each scheduled volume with the present composition.Shi Yi preparation can be by direct compacting or method of granulating preparation especially, and these preparations can contain conventional excipients such as binding agent, disintegrating agent, antitack agent and the disintegrating agent etc. of safety and effective dose.Tablet also can carry out coating according to any method well known by persons skilled in the art, and this coating does not hinder the releasing properties of tablet, or other physics of the present invention or chemical property.Above-mentioned preparation can also be modified by any method known to those skilled in the art to obtain the slow release of active constituent, and these preparations can also contain other active constituents of safety and effective dose, as antibacterial or antiseptic.
Pharmaceutical composition of the present invention can be used as the ingredient and the other drug preparation of therapeutic scheme and unites use.
Pharmaceutical composition of the present invention can also be packaged as goods, and these goods contain the zidovudine of safety and treatment effective dose, and valproic acid or its salt or the valpromide of safety and treatment effective dose.
Any packing well known by persons skilled in the art is suitable for oral tablet, scrotiform tablet or other solid dosage formss and can not destroys the distinct methods of component of the present invention, is applicable to and packs.The tablet, scrotiform tablet or other solid dosage formss that are suitable for oral administration can be packed and are contained in the multiple packaging material, particularly glass and plastic bottle also can be packaged in the unit dose blister packs.Can also print relevant label and the information of Pharmaceutical composition therewith on these packaging material.In addition, goods can comprise pamphlet, report or the leaflet that contains product information.This of pharmaceutical dosage form kind of form is called " adnexa in the packing " in pharmaceuticals industry.Adnexa can be attached to or be included in the pharmacy goods in the packing.Adnexa and any goods label provide the information relevant with Pharmaceutical composition in the packing.
Pharmaceutical composition of the present invention can be with being fit to normally used method of technical staff and technology preparation its physics and chemical characteristic and prepare peroral dosage form by direct compacting or method of granulating.
The invention effect:
David's mug(unit of measure) doctor Li Si in North Carolina, US university
[1]Research group valproic acid (valproic acid) is used for the test of the treatment of acquired immune deficiency syndrome (AIDS), screened the contraindication that does not have the valproic acid treatment, the AIDS the infected who does not accept interferon and the treatment of other immunomodulators, had 4 AIDS the infecteds and accepted this new therapeutic scheme.These the infecteds after accepting HAART, accepted again 3 months oral valproic acid (500～750mg/ days, bid) treatment.In the front and back that giving valproic acid treatment, cultivate the CD4+ cell of dormancy by limiting dilution assay, and the CD4+T cell of dormancy with latent infection is carried out quantitative assay.Result of the test shows, before adding valproic acid, the frequency that rest cell infects is stable, but after giving, just begin to reduce, this minimizing all is tangible in four patients' three people, in accepting the AIDSinfected patient of this therapeutic trial, there is HIV (human immunodeficiency virus) hiding in 3 human bodies obviously to reduce, amount of decrease reaches 75%.
Above-mentioned evidence is removed the CD4+T cell that can increase HIV dormancy in body safely as valproic acid or its salt of acetylation of histone enzyme inhibitor.
Zidovudine is one of common drug in the anti-AIDS treatment HAART, and the medical insurance catalogue that has entered China at present is one of essential drugs of treatment acquired immune deficiency syndrome (AIDS).Zidovudine belongs to efabirenz, by the cell kinase phosphorylation, form the triphosphoric acid zidovudine, the latter can be by selectivity suppresses the HIV Revertase with the competition of natural substrate triphosphoric acid deoxythymidylic acid, extend necessary 3 '-hydroxyl because zidovudine lacks DNA, therefore can stop HIV to duplicate by the extension that stops DNA chain inhibition viral DNA chain.Adult's recommended dose of zidovudine is 500mg/ days or 600mg/ days, part vic (per 4 hours clothes 100mg when clear-headed); Recommending 3 months to 12 years old child's dosages is per 6 hours 180mg/m
2, should not surpass per 6 hours 200mg/m
2
The advantage of valproic acid or its salt is that it is a kind of by clear cognitive medicine, is used to the long-term treatment of epilepsy, migraine and emotional maladjustment.Most of people have good toleration to it, fatality rate to the infant below 2 years old is 1: 8200, child to 3-10 year then is 1: 11, child and adult more than 200,10 years old, fatality rate is then almost nil, total fatality rate is 1: 51,300 (Bryant AE, the neurological 1986,40:465-469).
Therefore, above-mentioned Pharmaceutical composition not only can be removed the HIV that is activated, and can also remove the HIV that hides in human body cell, escapes the medicine attack.
Pharmaceutical composition of the present invention can be used as effective Drug therapy HIV-I and infects, and AIDS provides a kind of new way for treatment.
Embodiment
The following example has further described and has illustrated the particular in the scope of the invention.The embodiment that provides just illustrates, and is not will be as restriction, because under the prerequisite that does not deviate from the spirit and scope of the present invention, a lot of versions are possible.
Embodiment 1
1. the direct compacting preparation that contains the tablet of zidovudine and valproic acid
| Component | Content (g)/1000 slice |
| Zidovudine | 300 |
| Valproic acid | 275 |
| PVP (1% aqueous solution) | 3.75 |
| Tween 80 (1% dehydrated alcohol) | 7.5 |
| Microcrystalline Cellulose | 15 |
| CMS-Na | 20 |
| Magnesium stearate | 7.5 |
| Lactose | The surplus of gross weight |
| Gross weight | 750 |
2. preparation method
Zidovudine, valproic acid, lactose, microcrystalline Cellulose and the CMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent PVP (1% aqueous solution) and tween 80 (1% dehydrated alcohol) is made soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add magnesium stearate and make mixing behind the lubricant, tabletting, every heavy 0.75g.
Embodiment 2
1. the direct compacting preparation that contains the tablet of zidovudine and sodium valproate
| Component | Content (g)/1000 slice |
| Zidovudine | 300 |
| Sodium valproate | 300 |
| 95% ethanol | 8 |
| 2% tween (1% dehydrated alcohol) | 10 |
| cCMS-Na | 20 |
| Magnesium stearate | 4 |
| Pregelatinized Starch | The surplus of gross weight |
| Gross weight | 800 |
2. preparation method
Zidovudine, sodium valproate, pregelatinized Starch and the cCMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and 2% tween solution and make soft material in right amount, 20 mesh sieves are granulated, in 50-60 ℃ of drying, 20 mesh sieve granulate add magnesium stearate and make mixing behind the lubricant, tabletting, every heavy 0.80g.
Embodiment 3
1. the direct compacting preparation that contains the tablet of zidovudine and valproic acid
| Component | Content (g)/1000 slice |
| Zidovudine | 300 |
| Valproic acid | 250 |
| Pregelatinized Starch | 30 |
| 95% ethanol | 7 |
| 2% tween (1% dehydrated alcohol) | 7 |
| CMS-Na | 14 |
| Stearic acid | 3.5 |
| Micropowder silica gel | 3.5 |
| Lactose | The surplus of gross weight |
| Gross weight | 690 |
2. preparation method
Zidovudine, valproic acid, pregelatinized Starch, lactose, the CMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and 2% tween (1% dehydrated alcohol) solution and make soft material in right amount, 20 mesh sieves are granulated, in 50-60 ℃ of drying, 20 mesh sieve granulate add acid of hard ester and micropowder silica gel and make mixing behind the lubricant, tabletting, every weight 0.69g.
Embodiment 4
1. the direct compacting preparation that contains the tablet of zidovudine and sodium valproate
| Component | Content (g)/1000 slice |
| Zidovudine | 150 |
| Sodium valproate | 175 |
| cCMS-Na | 45 |
| 95% ethanol | 5 |
| Stearic acid | 5 |
| PEG400 | 2.5 |
| Lactose | The surplus of gross weight |
| Gross weight | 480 |
2. preparation method
Zidovudine, sodium valproate, lactose, the cCMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and make soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add acid of hard ester and PEG400 and make mixing behind the lubricant, tabletting, every weight 0.48g.
Embodiment 5
1. the direct compacting preparation that contains the tablet of zidovudine and magnesium valproate
| Component | Content (g)/1000 slice |
| Zidovudine | 300 |
| Magnesium valproate | 300 |
| PVP (1% aqueous solution) | 7.6 |
| Tween 80 (1% dehydrated alcohol) | 7.6 |
| Microcrystalline Cellulose | 15 |
| CMS | 15 |
| Magnesium stearate | 8 |
| Lemon yellow | 0.15 |
| Starch | The surplus of gross weight |
| Gross weight | 760 |
2. preparation method
Zidovudine, magnesium valproate, lactose, microcrystalline Cellulose, CMS and the lemon yellow of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent PVP (1% aqueous solution) and tween 80 (1% dehydrated alcohol) is made soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add magnesium stearate and make mixing behind the lubricant, tabletting, every heavy 0.76g.
Embodiment 6
1. the direct compacting preparation that contains the tablet of zidovudine and magnesium valproate
| Component | Content (g)/1000 slice |
| Zidovudine | 250 |
| Magnesium valproate | 275 |
| PVP (1% aqueous solution) | 7.2 |
| Tween 80 (1% dehydrated alcohol) | 7.2 |
| Microcrystalline Cellulose | 15 |
| CMS | 15 |
| Magnesium stearate | 8 |
| Lactose | The surplus of gross weight |
| Gross weight | 720 |
2. preparation method
Zidovudine, magnesium valproate, lactose, microcrystalline Cellulose, CMS and the lemon yellow of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent PVP (1% aqueous solution) and tween 80 (1% dehydrated alcohol) is made soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add magnesium stearate and make mixing behind the lubricant, tabletting, every heavy 0.72g.
Embodiment 7
1. the direct compacting preparation that contains the tablet of zidovudine and magnesium valproate
| Component | Content (g)/1000 slice |
| Zidovudine | 175 |
| Magnesium valproate | 150 |
| PVP (1% aqueous solution) | 4.7 |
| Tween 80 (1% dehydrated alcohol) | 4.7 |
| Microcrystalline Cellulose | 21 |
| CMS | 15 |
| Calcium stearate | 5 |
| Starch | The surplus of gross weight |
| Gross weight | 470 |
2. preparation method:
Zidovudine, magnesium valproate, lactose, microcrystalline Cellulose and the CMS of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent PVP (1% aqueous solution) and tween 80 (1% dehydrated alcohol) is made soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add magnesium stearate and make mixing behind the lubricant, tabletting, every heavy 0.47g.
Embodiment 8
1. the direct compacting preparation that contains the tablet of zidovudine and valproic acid calcium.
| Component | Content (g)/1000 slice |
| Zidovudine | 250 |
| Valproic acid calcium | 225 |
| Pregelatinized Starch | 40 |
| 95% ethanol | 7 |
| 2% tween (1% dehydrated alcohol) | 9 |
| CMS | 14 |
| Micropowder silica gel | 6.8 |
| Lactose | The surplus of gross weight |
| Gross weight | 620 |
2. preparation method
Zidovudine, valproic acid calcium, pregelatinized Starch, lactose, the CMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and 2% tween (1% dehydrated alcohol) solution and make soft material in right amount, 20 mesh sieves are granulated, in 50-60 ℃ of drying, 20 mesh sieve granulate add micropowder silica gel and make mixing behind the lubricant, tabletting, every heavy 0.62g.
Embodiment 9
1. the direct compacting preparation that contains the tablet of zidovudine and valproic acid calcium
| Component | Content (g)/1000 slice |
| Zidovudine | 300 |
| Valproic acid calcium | 300 |
| PVP (1% aqueous solution) | 8 |
| Tween 80 (1% dehydrated alcohol) | 7 |
| Microcrystalline Cellulose | 15 |
| CMS | 15 |
| Calcium stearate | 8 |
| Starch | The surplus of gross weight |
| Gross weight | 760 |
2. preparation method:
Zidovudine, valproic acid calcium, lactose, microcrystalline Cellulose and the CMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent PVP (1% aqueous solution) and tween 80 (1% dehydrated alcohol) is made soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add magnesium stearate and make mixing behind the lubricant, tabletting, every heavy 0.76g.
Embodiment 10
1. the direct compacting preparation that contains the tablet of zidovudine and valproic acid calcium
| Component | Content (g)/1000 slice |
| Zidovudine | 300 |
| Valproic acid calcium | 300 |
| PVP (1% aqueous solution) | 8 |
| Tween 80 (1% dehydrated alcohol) | 7 |
| Microcrystalline Cellulose | 15 |
| CMS | 15 |
| Calcium stearate | 8 |
| Lemon yellow | 0.38 |
| Starch | The surplus of gross weight |
| Gross weight | 760 |
2. preparation method
Zidovudine, valproic acid calcium, lactose, microcrystalline Cellulose, CMS and the lemon yellow of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent PVP (1% aqueous solution) and tween 80 (1% dehydrated alcohol) is made soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add calcium stearate and make mixing behind the lubricant, tabletting, every heavy 0.76g.
Embodiment 11
1. the direct compacting preparation that contains the tablet of zidovudine and valpromide.
| Component | Content (g)/1000 slice |
| Zidovudine | 300 |
| Valpromide | 225 |
| Pregelatinized Starch | 40 |
| 95% ethanol | 6.7 |
| 2% tween (1% dehydrated alcohol) | 9 |
| CMS-Na | 14 |
| Micropowder silica gel | 6.8 |
| Lactose | The surplus of gross weight |
| Gross weight | 670 |
2. preparation method
Zidovudine, valpromide, pregelatinized Starch, lactose, the CMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and 2% tween (1% dehydrated alcohol) solution and make soft material in right amount, 20 mesh sieves are granulated, in 50-60 ℃ of drying, 20 mesh sieve granulate add micropowder silica gel and make mixing behind the lubricant, tabletting, every heavy 0.67g.
Embodiment 12
1. the direct compacting preparation that contains the tablet of zidovudine and valpromide.
| Component | Content (g)/1000 slice |
| Zidovudine | 150 |
| Valpromide | 100 |
| Pregelatinized Starch | 40 |
| 95% ethanol | 4 |
| 2% tween (1% dehydrated alcohol) | 8 |
| CMS-Na | 12 |
| Micropowder silica gel | 2 |
| Hard ester acid | 2 |
| Lactose | The surplus of total amount |
| Gross weight | 400 |
2. preparation method
Zidovudine, valpromide, pregelatinized Starch, lactose and the CMS-Na of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and 2% tween (1% dehydrated alcohol) solution and make soft material in right amount, 20 mesh sieves are granulated, in 50-60 ℃ of drying, 20 mesh sieve granulate add acid of hard ester and micropowder silica gel and make mixing behind the lubricant, tabletting, every weight 0.4g.
Embodiment 13
1. the direct compacting preparation that contains the tablet of zidovudine and valpromide
| Component | Content (g)/1000 slice |
| Zidovudine | 325 |
| Valpromide | 200 |
| Pregelatinized Starch | 40 |
| 95% ethanol | 6.7 |
| 2% tween (1% dehydrated alcohol) | 9 |
| CMS-Na | 14 |
| Micropowder silica gel | 6.7 |
| Sunset yellow | 0.33 |
| Lactose | The surplus of gross weight |
| Gross weight | 670 |
2. preparation method
Zidovudine, valproic acid, pregelatinized Starch, lactose, CMS-Na and the sunset yellow of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and 2% tween (1% dehydrated alcohol) solution and make soft material in right amount, 20 mesh sieves are granulated, in 50-60 ℃ of drying, 20 mesh sieve granulate add micropowder silica gel and make mixing behind the lubricant, tabletting, every heavy 0.67g.
Embodiment 14
1. the direct compacting preparation that contains the tablet of zidovudine and sodium valproate
| Component | Content (g)/1000 slice |
| Zidovudine | 150 |
| Sodium valproate | 175 |
| cCMS-Na | 45 |
| 95% ethanol | 5 |
| Magnesium stearate | 5 |
| PEG400 | 2.5 |
| Sunset yellow | 0.48 |
| Lactose | The surplus of gross weight |
| Gross weight | 480 |
2. preparation method
Zidovudine, sodium valproate, lactose, cCMS-Na and the sunset yellow of above-mentioned recipe quantity are crossed 100 mesh sieves, mix homogeneously, cross 60 mesh sieves, add binding agent 95% ethanol and make soft material in right amount, 20 mesh sieves are granulated, in 80 ℃ of dryings, 20 mesh sieve granulate add magnesium stearate and PEG400 and make mixing behind the lubricant, tabletting, every heavy 0.48g.
Embodiment 15
1. the capsule that contains zidovudine and valproic acid
| Component | Content (g)/1000 slice |
| Zidovudine | 100 |
| Valproic acid | 100 |
| Pregelatinized Starch | 15.5 |
| Microcrystalline Cellulose (drying) | 70 |
| Carboxymethylstach sodium (drying) | 1.5 |
| Stearic acid | 3 |
| Gross weight | 290 |
2. preparation method
After above-mentioned recipe quantity raw material pulverizing crossed 60 mesh sieves, mix homogeneously was crossed 40 mesh sieves, adds stearic acid, and fill 3 behind the mix homogeneously
#Capsule, the tolerant heavy about 0.29g of every intragranular.
Embodiment 16
1. the capsule that contains zidovudine and sodium valproate
| Component | Content (g)/1000 |
| Zidovudine | 150 |
| Sodium valproate | 175 |
| Lactose | 66 |
| Microcrystalline Cellulose (drying) | 44 |
| Carboxymethylstach sodium (drying) | 2.2 |
| Sodium stearate | 2.8 |
| Gross weight | 440 |
2. preparation method
After above-mentioned recipe quantity raw material pulverizing crossed 60 mesh sieves, mix homogeneously was crossed 40 mesh sieves, adds sodium stearate, and fill 1 behind the mix homogeneously
#Capsule, the tolerant heavy about 0.44g of every intragranular.
Embodiment 17
1. the capsule that contains zidovudine and sodium valproate
| Component | Content (g)/1000 |
| Zidovudine | 100 |
| Sodium valproate | 150 |
| Starch | 30 |
| Microcrystalline Cellulose (drying) | 100 |
| Carboxymethylstach sodium (drying) | 16 |
| Sodium stearate | 4 |
| Gross weight | 400 |
2. preparation method
After above-mentioned recipe quantity raw material pulverizing crossed 60 mesh sieves, mix homogeneously was crossed 40 mesh sieves, adds sodium stearate, and fill 2 behind the mix homogeneously
#Capsule, the tolerant heavy about 0.4g of every intragranular.
Embodiment 18
1. the capsule that contains zidovudine and magnesium valproate
| Component | Content (g)/1000 |
| Zidovudine | 125 |
| Magnesium valproate | 150 |
| Starch | 41 |
| Microcrystalline Cellulose (drying) | 72 |
| Carboxymethylstach sodium (drying) | 10 |
| Magnesium stearate | 2.0 |
| Gross weight | 400 |
2. preparation method
After above-mentioned recipe quantity raw material pulverizing crossed 60 mesh sieves, mix homogeneously was crossed 40 mesh sieves, adds magnesium stearate, and fill 2 behind the mix homogeneously
#Capsule, the tolerant heavy about 0.4g of every intragranular.
Embodiment 19
1. the capsule that contains zidovudine and valproic acid calcium
| Component | Content (g)/1000 |
| Zidovudine | 150 |
| Magnesium valproate | 175 |
| Lactose | 66 |
| Microcrystalline Cellulose (drying) | 44 |
| Carboxymethylstach sodium (drying) | 2.2 |
| Calcium stearate | 2.8 |
| Gross weight | 440 |
2. preparation method
After above-mentioned recipe quantity raw material pulverizing crossed 60 mesh sieves, mix homogeneously was crossed 40 mesh sieves, adds calcium stearate, and fill 1 behind the mix homogeneously
#Capsule, the tolerant heavy about 0.44g of every intragranular.
Embodiment 20
1. the capsule that contains zidovudine and valpromide
| Component | Content (g)/1000 |
| Zidovudine | 150 |
| Valpromide | 75 |
| Starch | 32 |
| Microcrystalline Cellulose (drying) | 58 |
| Carboxymethylstach sodium (drying) | 12.0 |
| Sodium stearate | 3.0 |
| Gross weight | 330 |
2. preparation method
After above-mentioned recipe quantity raw material pulverizing crossed 60 mesh sieves, mix homogeneously was crossed 40 mesh sieves, adds sodium stearate, and fill 2 behind the mix homogeneously
#Capsule, the tolerant heavy about 0.33g of every intragranular.
Embodiment 20
1. the capsule that contains zidovudine and valpromide
| Component | Content (g)/1000 |
| Zidovudine | 150 |
| Valpromide | 75 |
| Lactose | 42 |
| Microcrystalline Cellulose (drying) | 58 |
| Carboxymethylstach sodium (drying) | 12.0 |
| Stearic acid | 3.0 |
| Gross weight | 340 |
2. preparation method
After above-mentioned recipe quantity raw material pulverizing crossed 60 mesh sieves, mix homogeneously was crossed 40 mesh sieves, adds stearic acid, and fill 2 behind the mix homogeneously
#Capsule, the tolerant heavy about 0.34g of every intragranular.
Claims (9)
1. Pharmaceutical composition that contains zidovudine and valproic acid or its salt, it is characterized in that: comprise zidovudine (AZT), the therapeutics combination of chemical name 3 '-azido-3 '-deoxyribosylthymine and valproic acid or its salt, the formula range of its Pharmaceutical composition, be by weight percentage: zidovudine 0.1～95%, valproic acid or its salt 1.0%～95% and pharmaceutic adjuvant 4～98.9%, pharmaceutic adjuvant are diluent, binding agent, disintegrating agent, lubricant, coloring agent and/or correctives.
2. the Pharmaceutical composition that contains zidovudine and valproic acid or its salt according to claim 1, it is characterized in that: in the per unit dosage form, contain 10～600mg zidovudine, 50～500mg valproic acid or its salt and account for the pharmaceutic adjuvant of unit dosage forms gross weight 15%～40%, pharmaceutic adjuvant is diluent, binding agent, disintegrating agent, lubricant, coloring agent and/or correctives.
3. the Pharmaceutical composition that contains zidovudine and valproic acid or its salt according to claim 1, it is characterized in that: the Pharmaceutical composition gross weight that contains zidovudine, valproic acid or its salt and pharmaceutic adjuvant is 100%, each constituent content is: 1. 0.1～95% zidovudine, 2. 1.0～95% valproic acid or its salt, 3. 0～35% diluent, 4. 0～20% binding agent, 5. 0～30% disintegrating agent, 6. 0～10% lubricant and 7. other pharmaceutically acceptable coloring agent and/or correctivess of 0～10%.
4. the Pharmaceutical composition that contains zidovudine and valproic acid or its salt according to claim 3 is characterized in that: diluent comprises one or more in lactose, sucrose, mannitol, sorbitol, starch, pregelatinized Starch, cellulose, processing agar, gelatin or the dextrin.
5. the Pharmaceutical composition that contains zidovudine and valproic acid or its salt according to claim 1 is characterized in that: binding agent comprises the water of one or more adjuvants in water, ethanol, tween 80, polyvinylpyrrolidone (PVP), hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium alginate, aluminium-magnesium silicate, arabic gum or the Polyethylene Glycol or the solution of alcohol.
6 Pharmaceutical compositions that contain zidovudine and valproic acid or its salt according to claim 1 is characterized in that: disintegrating agent comprises one or more in carboxymethyl starch sodium (CMS-Na), crosslinked carboxymethyl fecula sodium (cCMS-Na), low-substituted hydroxypropyl cellulose (LHPC), crospolyvinylpyrrolidone (PVPP), AmberliteIRP-88, sodium carboxymethyl cellulose (CMC-Na), cross-linking sodium carboxymethyl cellulose (cCMC-Na), carboxymethylcellulose calcium or the microcrystalline Cellulose (MCC).
7. the Pharmaceutical composition that contains zidovudine and valproic acid or its salt according to claim 1 is characterized in that: lubricant comprises one or more in magnesium stearate, calcium stearate, stearic acid, Polyethylene Glycol, silicon dioxide, micropowder silica gel, Pulvis Talci, aluminium hydroxide, 0.75% hydrated sodium aluminosilicate, sodium lauryl sulphate or the Stepanol MG.
8. the Pharmaceutical composition that contains zidovudine and valproic acid or its salt according to claim 1, it is characterized in that: the pharmaceutically acceptable coloring agent of used other comprises red, red scarlet, the light blue of coloring agent lemon yellow, sunset yellow, carmine, amaranth, temptation, indigo, light green, egg yolk and medicinal color lake, and correctives A Siba is sweet, in glycyrrhizin, stevioside, saccharin sodium or the medicinal essence one or more.
9. the Pharmaceutical composition that contains zidovudine and valproic acid or its salt according to claim 1 is characterized in that: valproic acid and salt thereof comprise valproic acid, sodium valproate, magnesium valproate, valproic acid calcium or derivant valpromide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510086716 CN1762377A (en) | 2005-10-26 | 2005-10-26 | Medicinal composition containing zidovudine, valproic acid or its salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510086716 CN1762377A (en) | 2005-10-26 | 2005-10-26 | Medicinal composition containing zidovudine, valproic acid or its salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1762377A true CN1762377A (en) | 2006-04-26 |
Family
ID=36746836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510086716 Pending CN1762377A (en) | 2005-10-26 | 2005-10-26 | Medicinal composition containing zidovudine, valproic acid or its salt |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1762377A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107096033A (en) * | 2017-06-23 | 2017-08-29 | 中国科学院广州生物医药与健康研究院 | A kind of pharmaceutical composition of anti AIDS virus and its application |
-
2005
- 2005-10-26 CN CN 200510086716 patent/CN1762377A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107096033A (en) * | 2017-06-23 | 2017-08-29 | 中国科学院广州生物医药与健康研究院 | A kind of pharmaceutical composition of anti AIDS virus and its application |
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