CN100536849C - Medicine composition containing theocin-like medicines and vitamin K - Google Patents
Medicine composition containing theocin-like medicines and vitamin K Download PDFInfo
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- CN100536849C CN100536849C CNB2006100439353A CN200610043935A CN100536849C CN 100536849 C CN100536849 C CN 100536849C CN B2006100439353 A CNB2006100439353 A CN B2006100439353A CN 200610043935 A CN200610043935 A CN 200610043935A CN 100536849 C CN100536849 C CN 100536849C
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Abstract
The present invention relates to a medicine composition containing theophyllines medicine and vitamin K for effectively curing respiratory diseases of asthma and chronic obstructive disease of lung, etc. Said medicine composition can be made into various different dosage forms.
Description
Technical field
The invention belongs to the new pharmaceutical composition of treatment respiratory system disease.
Background technology
Asthma is a kind of common respiratory system disease, and sickness rate has trend of rising year by year.Pathogenesis of asthma mechanism is very complicated, and is not clear and definite fully as yet so far.Once think a kind of airway smooth muscle dysfunction disease the 1950's, the essence that has proposed asthma the beginning of the eighties is airway hyperreactivity.Thinking that at present asthma is the air flue chronic inflammation disease that various kinds of cell and cell component participate in, is feature with pulmonary's reversibility airflow obstruction, the gentle road of air flue mucosa inflammation high response.
Nearest research shows that again the secular chronic inflammatory disease of asthmatic patient can cause airway remodeling, causes patient's pulmonary ventilation function to descend, and very easily brings out serious asthma attack.Beta-receptor agonist and corticosteroids medicine are to treat the most effectively medicine of respiratory system diseases such as asthma, chronic obstructive pulmonary disease at present clinically, but fundamentally, can not make the asthmatic patient recovery from illness, and the patient still needs to take medicine throughout one's life.In addition, the beta-receptor agonist exists bigger risk for the patient that heart disease is arranged in the use, be easy to bring out arrhythmia, and, for a lot of long-term asthma patients, cardiac disorders of various degrees all, this has more increased the risk of medication.In addition, the beta-receptor agonist has in use been covered the very serious airway inflammation symptom of asthmatic patient, be easy to bring out fatal asthma attack, and the corticosteroids medicine has powerful anti-inflammatory activity, but if whole body uses, untoward reaction is very serious, respiratory tract is local use to a lot of infant or advanced age the gerontal patient very inconvenient, and local use cost in the preparation of medicine raises, and this has strengthened patient's medical expense to a great extent.
Thereby it is low to seek to develop a kind of cost, and good effect can suppress the medicine of asthmatic patient airway remodeling, fundamentally cure asthma, alleviate patient's misery and huge medical expense, this meets the interests of extensive patients, and is significant for the harmonious society that builds us.
Theophylline class medicine is applied to the history in year surplus in the of clinical existing 60 as a kind of suppressing panting calming medicine.Along with novel anti-asthmatic medicament is continually developed, this type of medicine treatment status clinically descends to some extent.But because its low price is still the important drugs for the treatment of bronchial asthma in a lot of places at present.Intravenous injection aminophylline antiasthmatic effect is fast, good effect, and is clinical commonly used.But safety range is little, and the effective plasma level concentration range is narrow, and therapeutic index is narrow, and (10～20mg/ml), the factor that influences its pharmacokinetics is more, and body internal diabetes removal rates individual difference is bigger.If improper use, Chang Yi causes serious toxic and side effects, even threat to life.Clinical medicine dose is difficult to grasp.
The mechanism of action of theophylline class medicine is not thoroughly illustrated as yet, but result of study recently thinks that the antiasthmatic effect of theophylline class medicine is main relevant with following mechanism.(1) activity of inhibition phosphodiesterase; (2) antagonism adenosine receptor; (3) concentration of reduction intracellular calcium; (4) release of stimulation of endogenous catecholamine; (5) suppress mastocyte and discharge inflammatory mediator; (6) antiinflammatory action.
Theophylline class medicine and derivant thereof have more than 300 kinds.Theophylline class medicine comparatively commonly used clinically at present comprises Slow-release Theophylline, aminophylline, diprophylline (diprophylline), brontyl, Oxtriphylline, Glynazan, tripropyl xanthine and doxofylline etc.
Vitamin k 1 its chemical name is: 2-methyl-3-(3,7,11,15-tetramethyl-2-hexadecene base)-1,4-naphthalenedione.This product is a vitamin medicaments, is liver composition-factor II, VII, IX, the necessary material of X.Vitamin k lacks can cause these thrombin dyssynthesises or unusual, clinical visible bleeding tendency and prolonged prothrombin.Be mainly used in vitamin k and lack cause hemorrhage, as hemorrhage due to obstructive jaundice, leak, the chronic diarrhea etc., vitamin k lacks in the body due to the Hypoprothrombinemia due to Coumarins, the sodium salicylate etc., hemorrhage of newborn and prolonged application broad ectrum antibiotic.
Summary of the invention
The invention provides a kind of pharmaceutical composition that is used for the treatment of bronchial asthma, it is characterized in that it contains theophylline class medicine and vitamin k (Vk).
Our Lunan Pharmacy Co. Ltd passes through bronchial asthma pathogeny and physiopathologic further investigation, not obvious according to existing the medicine curative effect in the treatment of theophylline class clinical drug, shortcomings such as side effect is big, theophylline class medicine and vitamin k are formed compound recipe, be used for the treatment of respiratory system diseases such as bronchial asthma, obtained the unexpected effect that gets, we find in experiment, aminophylline and vitamin k compound recipe have good synergism, show evident in efficacy through a large amount of zooperies, and reduced theophylline class amount of drug, side effect significantly reduces, and has increased the safety of medication.Share obtaining ideal results like this aspect the respiratory system diseases such as treatment asthma for theophylline class medicine and vitamin K, is that our institute at the beginning of experiment is unexpected.The two share the obvious synergistic effect like this that why can obtain, and this is worth us to continue deep research.
We find also that in test not only aminophylline and vitamin K compound recipe have good synergism, aminophylline can be by brontyl, Oxtriphylline, Glynazan, diprophylline (diprophylline), the tripropyl xanthine, multiple theophylline class such as doxofylline medicine replaces, and can obtain good concertedness effect equally; Vitamin K can be vitamin k 1, vitamin k 2, vitamin k 3 or methylnaphthohydroquinone, and they all have good therapeutic effect to experimental rat model of asthma or chronic obstructive pulmonary disease rat.
We are according to the result of clinical trial, and with the proper dosage proportioning, it is manufactured becomes the compound preparation that makes things convenient for the patient to take with theophylline class medicine and vitamin k class medicine.We grope by experiment, find that oral administration and intestinal external administration can both reach good effect.Wherein oral administration we be applied to pharmaceutical composition of the present invention by preferred several dosage forms such as double-layer tablet, slow releasing tablet, dispersible tablet, oral cavity disintegration tablet, capsule, slow releasing capsule, soft capsule or drop pill.In double-layer tablet, dispersible tablet, capsular developmental research, preferably to one or more in the following adjuvant, they are starch, L-HPC (low-substituted hydroxypropyl cellulose), magnesium stearate, microcrystalline Cellulose, PVP (polyvinylpyrrolidone), micropowder silica gel, carboxymethyl starch sodium, tertiary butyl-4-hydroxy methyl phenyl ethers anisole, Pulvis Talci, vitamin E, Henan gelling starch, carboxymethyl starch sodium, lactose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, crospolyvinylpyrrolidone, crosslinked carboxymethyl fecula sodium; (hydroxypropyl emthylcellulose-4M), HPMC-15M (one or more in hydroxypropyl emthylcellulose-15M), glyceryl monostearate, ethyl cellulose, acrylic resin RS100, acrylic resin RL100, polyvinyl alcohol or the ethylene-vinyl acetate copolymer of preferred following slow-release auxiliary material hexadecanol, octadecanol, HPMC-4M in slow releasing tablet and the capsular development of slow release; Preferred one or more in following adjuvant vitamin E, PEG400, PEG-3 oleate (Polyethylene Glycol-3 olein), glycerol, gelatin, propylene glycol or the PEG-60 glyceryl isostearate (Polyethylene Glycol-60 glyceryl isostearate) in the development of soft capsule; Preferred one or more among following adjuvant PEG-1500 (Polyethylene Glycol-1500), PEG-2000 (Polyethylene Glycol-2000), PEG-4000 (Polyethylene Glycol-4000) or the PEG-6000 (Polyethylene Glycol-6000) in the development of drop pill.
Because asthma is a kind of chronic disease, needs long-term prescription.Asthmatic patient can produce repel psychology to taking medicine for a long time, for covering the bitterness of medicine, increases mouthfeel, and we are also with the oral tablet coating, comprising: sweet tablet, film coating.Increased patient's compliance behind the coating greatly.
We have selected injection, injection powder pin, spray, aerosol, powder spray, buccal tablet the intestinal external administration.Its preparation method and pharmaceutic adjuvant are common method and adjuvant thereof.
The specific embodiment
Now further specify content of the present invention, but range of application of the present invention is not limited to following example by following example.
Embodiment 1
A vitamin k 1 6g
Lactose 30g
Dried starch 55g
Carboxymethyl starch sodium 30g
12%PVP ethanol solution 150g
Magnesium stearate 2g
Preparation technology: lactose, carboxymethyl starch sodium, dried starch are crossed 80 mesh sieves, take by weighing the vitamin k 1 of recipe quantity, be dissolved in an amount of dehydrated alcohol, lactose, carboxymethyl starch sodium, dried starch mix homogeneously with recipe quantity, adding the 12%PVP ethanol solution granulates in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the magnesium stearate of recipe quantity in the dried granule.
B aminophylline 150g
Hydroxypropyl cellulose 65g
Pregelatinized Starch 10g
The ethanol solution 30g of 6%PVP
Magnesium stearate 2g
Preparation technology: aminophylline is crossed 100 mesh sieves, 80 mesh sieves are crossed in hydroxypropyl cellulose, pregelatinized Starch, take by weighing the aminophylline of recipe quantity and hydroxypropyl cellulose, pregelatinized Starch mix homogeneously, the ethanol solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the magnesium stearate of recipe quantity in the dried granule.
C, with above-mentioned a, two kinds of components of b adopt the bi-layer tablet press stamping promptly to get double-layer tablet.
Embodiment 2
A, vitamin k 3 3g
Hydroxypropyl emthylcellulose-4M 40g
Microcrystalline Cellulose 30g
The ethanol solution of 6%PVP is an amount of
Magnesium stearate 2g
Preparation technology: vitamin k 3 is crossed 100 mesh sieves, hydroxypropyl cellulose-4M, microcrystalline Cellulose are crossed 80 mesh sieves, take by weighing the vitamin k 3 of recipe quantity and hydroxypropyl cellulose-4M, microcrystalline Cellulose mix homogeneously, adding the 6%PVP ethanol solution granulates in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the magnesium stearate of recipe quantity in the dried granule.
B, diprophylline 150g
Lactose 20g
Sodium carboxymethyl cellulose 60g
95% alcoholic solution of 6%PVP is an amount of
Magnesium stearate 2g
Preparation technology: diprophylline is crossed 100 mesh sieves, sodium carboxymethyl cellulose, lactose are crossed 80 mesh sieves, take by weighing the diprophylline of recipe quantity and sodium carboxymethyl cellulose, lactose mix homogeneously, 95% alcoholic solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the magnesium stearate of recipe quantity in the dried granule.
C, with above-mentioned a, two kinds of components of b adopt the bi-layer tablet press punching press promptly to get double-layer tablet.
Embodiment 3
A brontyl 50g
Lactose 30g
Hydroxypropyl emthylcellulose-15M 20g
The 95% alcoholic solution 150g of 6%PVP
Rikemal B 200 2g
Preparation technology: brontyl is crossed 100 mesh sieves, lactose, hydroxypropyl emthylcellulose-15M cross 80 mesh sieves, take by weighing the brontyl of recipe quantity and lactose, hydroxypropyl emthylcellulose-15M mix homogeneously, 95% alcoholic solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the Rikemal B 200 of recipe quantity in the dried granule.
B, vitamin k 2 5g
Hydroxypropyl cellulose 15g
Dextrin 20g
The 95% alcoholic solution 50g of 6%PVP
Pulvis Talci 2g
Preparation technology: vitamin k 2 is crossed 100 mesh sieves, hydroxypropyl cellulose, dextrin are crossed 80 mesh sieves, take by weighing the vitamin k 2 of recipe quantity and hydroxypropyl cellulose, dextrin mix homogeneously, 95% alcoholic solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the Pulvis Talci of recipe quantity in the dried granule.
C, with above-mentioned a, two kinds of components of b adopt the bi-layer tablet press punching press promptly to get double-layer tablet.
Embodiment 4
Oxtriphylline 150g
Lactose 30g
Carboxymethyl starch sodium 30g
Microcrystalline Cellulose 18g
The ethanol solution 100g of 6%PVP
Magnesium stearate 2g
Preparation technology: Oxtriphylline is crossed 100 mesh sieves, lactose, carboxymethyl starch sodium, microcrystalline Cellulose are crossed 80 mesh sieves, take by weighing the Oxtriphylline of recipe quantity and lactose, carboxymethyl starch sodium, microcrystalline Cellulose mix homogeneously, adding the 6%PVP ethanol solution granulates in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the magnesium stearate of recipe quantity in the dried granule.
B, vitamin k 3 5g
Hydroxypropyl cellulose 15g
Pregelatinized Starch 10g
The ethanol solution 30g of 6%PVP
Rikemal B 200 1g
Preparation technology: vitamin k 3 is crossed 100 mesh sieves, 80 mesh sieves are crossed in hydroxypropyl cellulose, pregelatinized Starch, take by weighing the vitamin k 3 of recipe quantity and hydroxypropyl cellulose, pregelatinized Starch mix homogeneously, the ethanol solution that adds 6%PVP is granulated in right amount, 60 ℃ of dryings, 16 mesh sieves are put in order dried granule, add the Rikemal B 200 of recipe quantity in the dried granule.
C, with above-mentioned a, two kinds of components of b adopt the bi-layer tablet press stamping promptly to get double-layer tablet.
Embodiment 5
A, Glynazan 150g
Celphere 250g
7%PVP solution (solvent is 90% ethanol) 200g
Preparation technology: Glynazan is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Drive granulating and coating machine (Taiwan unit becomes machinery plant), go into wind pressure 0.5bar, 30 ℃ of inlet air temperature, spray gun pressure (CYL) 3bar, atomizing pressure (CAP1) 0.8bar, pour celphere into, pelletize, blanking velocity 4rpm, the pump 12% of wriggling, rotary speed 145rpm, spray 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 50 ℃ of oven dry, discharging.
B, vitamin k 4 3g
Celphere 90g
7%PVP solution (solvent is 90% ethanol) 50g
Preparation technology: vitamin k 4 is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, 30 ℃ of inlet air temperature, CYL3bar, CAP1 0.8bar pours celphere into, pelletize, blanking velocity 4rpm, the pump 6% of wriggling, rotary speed 160rpm, spray 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 45 ℃ of oven dry, discharging.
C, the piller that a and b are made adopts hard capsule medicine filling machine to be respectively 150mg according to the weight that contains Glynazan and vitamin k 4 in per two capsules and 3mg fills, and gets final product.
Embodiment 6
A, tripropyl xanthine 100g
Celphere 200g
7%PVP solution (solvent is 90% ethanol) 200g
Preparation technology: the tripropyl xanthine is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, 30 ℃ of inlet air temperature, CYL3bar, CAP1 0.8bar pours celphere into, pelletize, blanking velocity 4rpm, the pump 12% of wriggling, rotary speed 165rpm sprays into 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 50 ℃ of oven dry, discharging.
B, vitamin k 3 3g
Celphere 150g
7%PVP solution (solvent is 90% ethanol) 150g
Preparation technology: vitamin k 3 is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, 30 ℃ of inlet air temperature, CYL3bar, CAP1 0.8bar pours celphere into, blanking velocity 4rpm, the pump 12% of wriggling, rotary speed 120rpm sprays into 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 45 ℃ of oven dry, discharging.
C, the piller that a and b are made adopts hard capsule medicine filling machine to be respectively 150mg according to the weight that contains tripropyl xanthine and vitamin k 3 in per two capsules and 3mg fills, and gets final product.
Embodiment 7
A, doxofylline 300g
Celphere. 300g
7%PVP solution (solvent is 90% ethanol) 200g
Preparation technology: doxofylline is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, 30 ℃ of inlet air temperature, CYL3bar, CAP1 0.8bar pours celphere into, pelletize, blanking velocity 4rpm, the pump 12% of wriggling, rotary speed 145rpm sprays into 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 50 ℃ of oven dry, discharging.
What make among b, a contains the doxofylline piller
Ethyl cellulose 40g
Stearic acid 70g
Polyethylene Glycol-6000 6g
Pulvis Talci 12g
95% ethanol 1000g
Preparation technology: the doxofylline piller that contains that makes among a is poured in the hopper.Drive the granulating and coating machine, 30 ℃ of inlet air temperature are gone into wind pressure 0.5bar, 30 ℃ of inlet air temperature, and CYL3bar, CAP1 1.0bar, the pump 6% of wriggling, rotary speed 175rpm sprays into 95% alcoholic solution of ethyl cellulose, stearic acid and Polyethylene Glycol-6000.Coating finishes, 50 ℃ of oven dry, discharging.
C, vitamin k 2 3g
Celphere 150g
7%PVP solution (solvent is 90% ethanol) 150g
Preparation technology: vitamin k 2 is crossed 120 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper, drives the granulating and coating machine, goes into wind pressure 0.5bar, 30 ℃ of inlet air temperature, and CYL3bar, CAP1 0.8bar pours celphere into, pelletize.Blanking velocity 4rpm, the pump 12% of wriggling, rotary speed 120rpm sprays into 7%PVP solution (solvent is 90% ethanol).Pelletize finishes, 45 ℃ of oven dry, discharging.
D, the piller that b and c are made adopts hard capsule medicine filling machine to be respectively 300mg according to the weight that contains doxofylline and vitamin k 2 in per two capsules and 3mg fills, and gets final product.
Embodiment 8.
Vitamin K and the medication combined use of theophylline class are to the pharmacodynamic experiment of experimental rat model of asthma
Experiment purpose:
Utilize the content of measuring the lung tissue of rats hydroxyproline, differential blood count, the swimming time of rat is observed speed and is sent out the inhibitory action of investigating the bronchial asthma that theophylline and vitamin k compound medicament composition bring out ovalbumin the incubation period of phase symptoms of asthma and asthma.
Be subjected to the reagent thing:
The pharmaceutical composition of vitamin k and aminophylline compound recipe.
Group is provided with:
Blank group, model group, Dexamethasone group, aminophylline group, vitamin k group, aminophylline and the high, medium and low dosage group of vitamin k compound recipe.
Gastric infusion dosage:
Dexamethasone 0.0875mg/kg, aminophylline 23mg/kg, vitamin k 0.46mg/kg, aminophylline and the high, medium and low dosage of vitamin k compound recipe are respectively 46mg/kg aminophylline+0.92mg/kgVk, 23mg/kg aminophylline+0.46mg/kgVk, 11.5mg/kg aminophylline+0.23mg/kgVk.
Operating procedure:
The preparation of rat asthmatic model: 64 SD rats, body weight are 260～360g, are divided into 8 groups at random by body weight, 8 every group.Irritate stomach respectively and give different medicines, model group is irritated stomach and is given pure water in contrast.Each group is 5% ovalbumin of lumbar injection prepared fresh (1ml/ only) and white hundred broken vaccines (0.1ml/ only) respectively, strengthen once after 5 days.Atomizing sucks 1% ovalbumin solution after 10 days, once a day, 15min/ time, continuous 35 days.Each organizes gastric infusion respectively, continuous irrigation stomach 35 days simultaneously.
Rat speed is sent out bringing out of phase asthma: attack with 1% ovalbumin and the atomizing of 2% acetylcholine, bring out asthma, observe the incubation period and the symptoms of asthma of each group.
Bronchoalveolar lavage fluid differential blood count: lumbar injection 3% pentobarbital sodium, 45mg/kg, anesthetized rat.The ventral aorta blood-letting causes death, and wins whole lung and part bronchus and carries out alveolar wass, before the lavation left lung is carried out ligation, extracts the back lavation.Phosphate buffer (PBS liquid) 9ml/ lung, the centrifugal 10min of irrigating solution 1500r/min, abandoning supernatant, precipitation adds 100 μ l normal saline and fully dissolves.The making blood smear that takes a morsel is with the leukocyte of observing behind Rui-Te dyeing 3min on the blood smear, with numeration of leukocyte plate microscopically counting.The left lung of extracing-20 is ℃ frozen, and pending chloramine-t method is measured collagen content.
The preparation of PBS irrigating solution: sodium chloride (NaCl) 8.0g, potassium chloride (KCl) 0.20g, sodium hydrogen phosphate (Na
2HPO
412H
2O) 2.90g, potassium dihydrogen phosphate (KH
2PO
4) 0.20g, sodium bicarbonate (NaHCO
3) 0.5g, add the 1000ml distilled water.
The preparation of the PBS liquid of using when making blood smear: potassium dihydrogen phosphate (KH
2PO
4) 0.3g, sodium hydrogen phosphate (Na
2HPO
4) 0.2g, add the 1000.0ml distilled water.
Chloramine-t method is measured the content of collagen protein: get frozen lung tissue, take by weighing 0.5g after thawing, add the homogenate of 2ml water for injection, be settled to 8ml, put into the teat glass of 20ml, add 8ml, the hydrochloric acid of 6mol/L places test tube and seals with absorbent cotton.Temperature is the interior pyrohydrolysis 17h of 120 ℃ sterilization cabinet, and hydrolyzed solution about reuse 1mol/L hydrochloric acid or sodium hydroxide accent PH to 6, is settled to 25ml with water for injection with the neutralization of 15mol/L sodium hydroxide at last, filters.
Getting respectively and organizing filtrate 2.0ml, control tube is 2.0ml water for injection, adds successively:
(1) 0.1mol/L citrate buffer solution 0.5ml and 0.05mol/L chloramine-T solution 1.0ml mixing.37 ℃ of water dissolution 25min.
(2) 3.15mol/L crosses solution chlorate 1.0ml mixing, acts on 5min under the room temperature.
(3) 10% paradime thylaminobenzaldehyde solution 1.0ml, mixing, 100 ℃ of boiling water 3min colour developings.
(4) ice bath cooling, absorbance A (560nm) is measured in the blank zeroing.
The content of A560nm and hydroxyproline is the positive line sexual relationship, and nearly all hydroxyproline all is present in the collagen, and therefore, the mensuration of hydroxyproline content becomes weighs the metabolic important indicator of body collagen tissue.Draw thus, A560nm value and collagen content are the positive line sexual relationship.
The mensuration of swimming time: 2% ovalbumin atomizing is attacked 15min and is drawn and breathe heavily, and each group rat is put into bucket for per two one group swim, and water temperature is 32 ℃.Measure and respectively organize swimming time.
Experimental result:
1. aminophylline and vitamin k compound recipe are attacked the influence of back incubation period and symptoms of asthma to sensitization rat antigen
In the rat of test group, aminophylline and vitamin k compound recipe high dose have significant coordinate repression to symptoms of asthma, have prolonged the incubation period of bronchial asthma morbidity greatly.Concrete experimental result sees Table 1.
Table 1 aminophylline and vitamin k compound recipe are attacked the influence of back incubation period and symptoms of asthma to sensitization rat antigen
*Compare P＜0.05 with model group
※Compare P＜0.05 with Dexamethasone group
﹠amp;Compare P＜0.05 with the aminophylline group
#Compare P＜0.05 with the Vk group
2. aminophylline and vitamin k compound recipe are to the influence of total white blood cells and differential counting in the bronchoalveolar lavage fluid of sensitization rat antigen attack back
Total white blood cells and eosinophilic granulocyte, Monocytes bacterium have significant increase in the experimental rat model of asthma bronchoalveolar lavage fluid, and vitamin k is to differential blood count and almost not influence of total white blood cells, and aminophylline has certain inhibitory action to it.Aminophylline and vitamin k compound recipe drug combination have been obtained significant concertedness inhibitory action to leukocytic increase in the bronchoalveolar lavage fluid, and exist tangible dose dependent, and concrete experimental result sees Table 2.
Table 2 aminophylline and vitamin k compound recipe are to the influence of total white blood cells in the bronchoalveolar lavage fluid and differential counting
*Compare P＜0.05 with model group
※Compare P＜0.05 with Dexamethasone group
﹠amp;Compare P＜0.05 with the aminophylline group
#Compare P＜0.05 with the Vk group
3. aminophylline group and vitamin k compound recipe are to the influence of experimental rat model of asthma lung tissue hydroxyproline content
Aminophylline group and vitamin k group respectively with model group there was no significant difference relatively, compound recipe group dose dependent has reduced the absorbance (A560) of hydroxyproline, and aminophylline and vitamin K obtained significant concertedness effect, concrete experimental result sees Table 3.
Table 3. aminophylline and vitamin k compound recipe are to the influence of lung tissue hydroxyproline content
*Compare P＜0.05 with model group
※Compare P＜0.05 with Dexamethasone group
#Compare P＜0.05 with the aminophylline group
﹠amp;Compare P＜0.05 with the Vk group
4. aminophylline and vitamin k compound recipe are to the influence of experimental rat model of asthma swimming time
Dexamethasone group and the aminophylline group model group there was no significant difference of comparing.The compound recipe group relatively has significant difference with aminophylline group, vitamin k group respectively, and especially high dose group difference is the most remarkable.Concrete experimental result sees Table 4.
Table 4. aminophylline and vitamin k compound recipe are to the influence of experimental rat model of asthma swimming time
*Compare P＜0.05 with model group
※Compare P＜0.05 with Dexamethasone group
﹠amp;Compare P＜0.05 with the aminophylline group
#Compare P＜0.05 with the Vk group
Aminophylline of in embodiment 8, being set forth and vitamin K compound recipe, aminophylline can be by brontyl, Oxtriphylline, Glynazan, the tripropyl xanthine, multiple theophylline class such as doxofylline medicine replaces, and can obtain good concertedness effect equally; Vitamin K can be vitamin k 1, vitamin k 2, vitamin k 3 or methylnaphthohydroquinone, and they all have good therapeutic effect to experimental rat model of asthma or chronic obstructive pulmonary disease rat.
Claims (8)
1. pharmaceutical composition for the treatment of respiratory system disease is characterized in that it is made up of following ingredients:
1) active component: theophylline class medicine and vitamin k;
2) pharmaceutically acceptable auxiliaries.
2. pharmaceutical composition as claimed in claim 1 is characterized in that, described theophylline class medicine is a kind of in following: aminophylline, brontyl, Oxtriphylline, Glynazan, tripropyl xanthine, doxofylline.
3. pharmaceutical composition as claimed in claim 1 is characterized in that, described vitamin k is a kind of in following: vitamin k 1, vitamin k 2, vitamin k 3 or methylnaphthohydroquinone.
4. pharmaceutical composition as claimed in claim 1 is characterized in that, it is double-layer tablet, slow releasing tablet, dispersible tablet, capsule, slow releasing capsule, soft capsule or drop pill.
5. pharmaceutical composition as claimed in claim 4, it is characterized in that, described double-layer tablet, dispersible tablet or capsule are except that containing theophylline class medicine and vitamin k class medicine, also contain in the following adjuvant one or more, they are starch, low-substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline Cellulose, polyvinylpyrrolidone, micropowder silica gel, carboxymethyl starch sodium, the tertiary butyl-4-hydroxy methyl phenyl ethers anisole, Pulvis Talci, vitamin E, the Henan gelling starch, lactose, sodium carboxymethyl cellulose, carboxymethylcellulose calcium, crospolyvinylpyrrolidone, crosslinked carboxymethyl fecula sodium.
6. pharmaceutical composition as claimed in claim 4, it is characterized in that, described slow releasing tablet or slow releasing capsule also contain in slow-release auxiliary material hexadecanol, octadecanol, hydroxypropyl emthylcellulose-4M, hydroxypropyl emthylcellulose-15M, glyceryl monostearate, ethyl cellulose, acrylic resin RS100, acrylic resin RL100, polyvinyl alcohol or the ethylene-vinyl acetate copolymer one or more except that containing theophylline class medicine and vitamin k class medicine.
7. pharmaceutical composition as claimed in claim 4, it is characterized in that, described soft capsule also contains in vitamin E, PEG400, Polyethylene Glycol-3 oleate, glycerol, gelatin, propylene glycol or Polyethylene Glycol-60 glyceryl isostearate one or more except that containing theophylline class medicine and vitamin k class medicine.
8. pharmaceutical composition as claimed in claim 4, it is characterized in that, described drop pill also contains in Polyethylene Glycol-1500, Polyethylene Glycol-2000, Polyethylene Glycol-4000 or the Polyethylene Glycol-6000 one or more except that containing theophylline class medicine and vitamin k class medicine.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2006100439353A CN100536849C (en) | 2006-05-10 | 2006-05-10 | Medicine composition containing theocin-like medicines and vitamin K |
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|---|---|---|---|
| CNB2006100439353A CN100536849C (en) | 2006-05-10 | 2006-05-10 | Medicine composition containing theocin-like medicines and vitamin K |
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| CN100536849C true CN100536849C (en) | 2009-09-09 |
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| CNB2006100439353A Active CN100536849C (en) | 2006-05-10 | 2006-05-10 | Medicine composition containing theocin-like medicines and vitamin K |
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| MX2008010233A (en) * | 2008-03-10 | 2009-11-10 | Eurodrug Lab B V | Modified release composition comprising doxofylline. |
| CN101716162B (en) * | 2009-11-26 | 2012-11-14 | 扬州中宝制药有限公司 | Aminophylline slow-release capsules and preparation method thereof |
| CN102697719B (en) * | 2012-06-20 | 2013-07-31 | 广州安健实业发展有限公司 | Oily drug composition containing vitamin K1 |
| CN102688191B (en) * | 2012-06-20 | 2013-07-31 | 广州安健实业发展有限公司 | Medicine composition containing vitamin K1 and oil |
| CN109701012A (en) * | 2019-03-01 | 2019-05-03 | 龙阔（苏州）生物工程有限公司 | A kind of vaccine adjuvant and its application and porcine reproductive and respiratory syndrome vaccine |
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Non-Patent Citations (2)
| Title |
|---|
| 维生素K_3与氨茶碱治疗小儿喘憋性肺炎的疗效对此观察——附60例临床总结. 戚进等.工企医刊，第7卷第2期. 1994 |
| 维生素K_3与氨茶碱治疗小儿喘憋性肺炎的疗效对此观察——附60例临床总结. 戚进等.工企医刊，第7卷第2期. 1994 * |
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