CN103705479A - Meloxicam sustained release tablet used for pet and preparation method thereof - Google Patents

Abstract

The invention discloses a meloxicam sustained release tablet used for a pet and a preparation technology thereof. The meloxicam sustained release tablet is stable to release and safe to administrate and comprises solid meloxicam dispersoid, a sustained release material, a filling material, an adhesive, a lubricant and a corrigent. The meloxicam sustained release tablet has the characteristics of convenient administration, rapid and lasting effects and stable curative effects.

Description

Meloxicam slow releasing tablet and preparation method thereof for a kind of house pet

Technical field

The invention belongs to veterinary drug preparation field, particularly meloxicam slow releasing tablet and preparation method thereof for a kind of house pet.

Background technology

Meloxicam (Meloxicam), for the NSAID (non-steroidal anti-inflammatory drug) of new generation that nineteen nineties develops, is mainly used in pet dog, cat.Quinolones coccidiostat, because having, it optionally suppresses II type cyclooxygenase (COX-2), it is a kind of II type cyclooxygenase-2 inhibitors of Oral Gastrointestinal Tract side effect minimum in similar nonsteroidal anti-inflammatory drug, also have antiinflammatory action strong, antipyretic effective, oral absorption is good and complete simultaneously, bioavailability is high, long half time, taking dose is few, without advantages such as nephrotoxicity.Therefore on house pet market, meloxicam has determined curative effect equally, toleration is strong, and the advantage less to gastrointestinal side effect also enjoys clinical house pet doctor's preference.The product of meloxicam Shi You Boehringer Ingelheim company exploitation the earliest, also be that current FDA ratifies one of a few NSAID (non-steroidal anti-inflammatory drug) for dog cat simultaneously, the dosage form of meloxicam in clinical practice mainly contains tablet, oral administration mixed suspension and injection at present, this medicine has stronger analgesia, antiinflammatory action, is mainly used in treating osteoarthritis and rheumatoid arthritis.But meloxicam, in clinical practice, because its dissolubility in water is low, causes its bioavailability low.In order to improve bioavailability, to facilitate clinical practice, we have great importance by meloxicam slow releasing tablet by the house pet of exploitation.

Patent (CN1708307B, December in 2011 7 days is open) a kind of water-soluble granular that comprises meloxicam is provided, mainly by meloxicam, meglumine, sugar, polyvidone etc., formed, major advantage is water solublity and the palatability that has strengthened meloxicam, facilitated clinical administration, but there are two shortcomings: the first, dosage is inaccurate; The second, administration frequently easily causes blood concentration fluctuation excessive, and the therapeutic effect impact during on clinical treatment is larger.Patent (CN102525974A, on July 4th, 2012 is open) meloxicam tablet and preparation method thereof for a kind of dog cat is provided, mainly by meloxicam, lactose, microcrystalline Cellulose, hyprolose, sodium citrate, cross-linking polyethylene pyrrolidone, pvpK30, aspartame, magnesium stearate, formed, major advantage is to reduce GI irritation, shortcoming is: one, meloxicam dissolution is low, is unfavorable for absorbing; Two, palatability is bad.

Summary of the invention

Based on above reason, the invention discloses house pet meloxicam slow releasing tablet, original administering mode once a day can be reduced to two days once, reduced the undue fluctuation of blood drug level, improve clinical therapeutic efficacy, and reduced the risk coming to harm, and by adding correctives, the palatability of having improved to greatest extent meloxicam, has facilitated clinical administration.

Inventor, through long term test, pays creative work, has obtained following embodiment:

1, a kind of house pet is comprised of following component by meloxicam slow releasing tablet: meloxicam solid dispersion; Slow controlled-release material, filler, binding agent, lubricant and correctives form.

2, described meloxicam solid dispersion is by meloxicam and meglumine are dissolved in aqueous solution jointly, the solid dispersion obtaining by vacuum drying, the mol ratio of its Meloxicam and meglumine is 8:10, the effective content that its effective dose is every Meloxicam: 0.2mg～3mg.

3, described slow controlled-release material is one or more the combination in sodium alginate, hydroxypropyl emthylcellulose, carbomer, and consumption is 20-25%(W/W).

4, described filler is starch and lactose, and starch consumption is 20-25%(W/W), lactose consumption is 34-43%(W/W); Binding agent is polyvidone, and consumption is 2.4-3%(W/W); Lubricant is one or more combinations in Pulvis Talci, micropowder silica gel, magnesium stearate, preferred magnesium stearate, consumption is 0.5%(W/W); Correctives is one or more combinations in the dry liver of the animals such as cattle, sheep, pig, fowl or muscle powder, fruity perfume, vanilla flavor, preferred Hepar Gallus domesticus powder, consumption is 8-12%(W/W).

5, suitability for industrialized production implementation step:

A, first to produce the solid dispersion of meloxicam and meglumine, meloxicam and meglumine are dissolved in the water jointly, carry out vacuum drying, dried pressed powder is pulverized, cross 200 mesh sieves, standby;

B, by the meloxicam solid dispersion after sieving, controlled slowly releasing adjuncts, filler, 80% correctives and 30% binding agent mix homogeneously;

C, add ethanol/water (30/70) the solution mix homogeneously of residue 70% binding agent, soft material processed;

D, the soft material making is carried out to wet granulation, dry 1 hour granulate for 60 ℃;

E, to the correctives mix homogeneously that adds lubricant and residue 20% in the granule making;

F, tabletting, obtain finished product.

The invention has the beneficial effects as follows:

1, house pet has not only kept whole effective ingredient of crude drug by meloxicam slow releasing tablet, owing to adopting slow release technique, can make reach rapidly maximum plasma concentration and can maintain for a long time this Cmax after drug oral, thereby effectively control hypertension.

2, easy to use, production technology is simple, is easy to extension and produces.

The specific embodiment:

Embodiment 1

Prescription:

Preparation method:

A, first to produce the solid dispersion of meloxicam and meglumine, meloxicam and meglumine are dissolved in the water jointly, carry out vacuum drying, dried pressed powder is pulverized, cross 200 mesh sieves, standby;

B, by the meloxicam solid dispersion after sieving, controlled slowly releasing adjuncts, filler, 80% correctives and 30% binding agent mix homogeneously;

C, add ethanol/water (30/70) the solution mix homogeneously of residue 70% binding agent, soft material processed;

D, the soft material making is carried out to wet granulation, dry 1 hour granulate for 60 ℃;

E, to the correctives mix homogeneously that adds lubricant and residue 20% in the granule making;

F, tabletting, obtain finished product.

Embodiment 2 stability tests

1 materials and methods

1.1 testing of materials medicines: for respectively according to embodiment 1-A, embodiment 1-B, the prepared meloxicam slow releasing tablet of embodiment 1-C; Contrast medicine: according to patent (CN102525974A, on July 4th, 2012 is open) self-control meloxicam tablet, content is 0.2mg.

1.2 methods are got respectively test drug and are contrasted each 180 of medicines, according to < < veterinary drug stability test technical specification (trying) > >, carried out the accelerated test six months of medicine, respectively at sampling in the 0th, 1,2,3,6 month, carry out assay.

2 result of the tests

Embodiment 2 medicine stability test results (n=4)

Result demonstration, the medicine stability of the meloxicam slow releasing tablet that embodiment 1-A, embodiment 1-B, embodiment 1-C make will obviously be better than contrasting the stability of medicine.Illustrate that this preparation is stable.

Embodiment 3 clinical trials

1. materials and methods

1.1 test material

1.1.1 trial drug test drug: embodiment 1-C, is used in conjunction seven days; Control drug: according to patent (CN102525974A, on July 4th, 2012 is open) self-control meloxicam tablet, content is 5mg.

1.1.2 experimental animal Tianjin pet clinic is diagnosed as the sick dog of osteoarthritis sufferer, has made a definite diagnosis ill dog for 80, age of onset 9-13 year.

1.2 test methods: by 80 dogs of natural occurrence, be divided into totally five groups of I, II, III, IV, V, every group of 16 dogs, I organizes as infecting not treatment group; II group is for adopting low dosage test drug treatment group (oral by per kilogram of body weight first administration 0.1mg, rechallenge is 0.05mg, and two days once, is used in conjunction 5 times); III group is dosetest medicine treatment group in adopting (oral by per kilogram of body weight first administration 0.2mg, rechallenge is 0.1mg, and two days once, is used in conjunction 5 times); IV group is for adopting high dose test drug treatment group (oral by per kilogram of body weight first administration 0.4mg, rechallenge is 0.2mg, and two days once, is used in conjunction 5 times); V group is for adopting control drug treatment group (oral by per kilogram of body weight first administration 0.2mg, rechallenge is 0.1mg, once a day, is used in conjunction 10 times).

Curative effect determinate standard

Cure rate: after off-test, the state of an illness, appetite, the clinical symptoms dog that recovers to fall ill normally completely accounts for the ratio of the total morbidity of this group dog.

Effective percentage: after off-test, the state of an illness, appetite, clinical symptoms take a turn for the better and the dog that recovers to fall ill normally accounts for the ratio of the total morbidity of this group dog to some extent.

Mortality rate: after in off-test or process of the test, the morbidity dog dying of illness because of arthritis accounts for the always ratio of morbidity dog of this group.

2 result of the tests:

Article 80, after the medication of morbidity dog difference, observe day by day clinical efficacy, its outcome record following (referring to the experimental effect result in table).III and Group IV: the 1st afternoon, has disease symptom; The 3rd day, 16 dog symptoms alleviated gradually; The 5th day, arthroncus disappeared, and ill dog walks normal; The 7th day, all rehabilitations; To the 10th day, without recurrence.And low dose group situation take a favorable turn, but never return to one's perfect health, need continued treatment; Control drug group treatment the 5th day time again bar dog there is vomiting phenomenon, gastroscopic observation gastric mucosa has bleeding, the therapeutic effect of all the other dogs is similar to Group III.Each mortality rate, cure rate, effective percentage, average weight gain amount of organizing dog in Table.

Embodiment 3 clinical verification test efficacy results

The cure rate of cure rate and high, the middle dosage group of effective percentage embodiment is higher, is 100%, and effective percentage is also higher, is 100%.

3 conclusions

3.1 embodiment are used for the treatment of the ill dog of osteoarthritis and have good therapeutic effect, and wherein, middle and high dosage group cure rate is significantly better than low dose group, and clinical practice safe effect is better than control drug group.But consider dosage group in economic factor recommendation clinical practice.

3.2 through the safety testing of healthy dogs (recommended dose 3 times take 3 times) is shown, has no clinical Novel presentation between the operating period, and healthy dogs is had no significant effect, and illustrates that this preparation is safe.

Claims (7)

1. a house pet meloxicam slow releasing tablet, comprises:

(1) meloxicam solid dispersion;

(2) slow controlled-release material;

(3) filler;

(4) binding agent;

(5) lubricant;

(6) correctives.

2. house pet claimed in claim 1 meloxicam slow releasing tablet, it is characterized in that described meloxicam solid dispersion is by meloxicam and meglumine are dissolved in aqueous solution jointly, the solid dispersion obtaining by vacuum drying, the mol ratio of meloxicam and meglumine is 8:10.

3. house pet claimed in claim 1 meloxicam slow releasing tablet, the content that it is characterized in that described meloxicam is 0.2mg～3mg/ sheet.

4. house pet claimed in claim 1 meloxicam slow releasing tablet, described slow controlled-release material is one or more the combination in sodium alginate, hydroxypropyl emthylcellulose, carbomer, consumption is 20-25%(W/W).

5. house pet claimed in claim 1 meloxicam slow releasing tablet, is characterized in that described filler is starch and lactose; Binding agent is polyvidone, water, dehydrated alcohol; Lubricant is one or more combinations in Pulvis Talci, micropowder silica gel, magnesium stearate; Correctives is one or more combinations in the dry liver of the animals such as cattle, sheep, pig, fowl or muscle powder, fruity perfume, vanilla flavor.

6. house pet claimed in claim 5 meloxicam slow releasing tablet, is characterized in that described filler is starch, lactose, and starch consumption is 20-25%(W/W), lactose consumption is 34-43%(W/W); Described binding agent is polyvidone, and consumption is 2.4-3%(W/W); Described lubricant is magnesium stearate, and consumption is 0. 5%(W/W); Described correctives is Hepar Gallus domesticus powder, and consumption is 8-12%(W/W).

7. a house pet meloxicam slow releasing tablet, its preparation realizes by following technology path:

A, first to produce the solid dispersion of meloxicam and meglumine, meloxicam and meglumine are dissolved in the water jointly, carry out vacuum drying, dried pressed powder is pulverized, cross 200 mesh sieves, standby;

B, by the meloxicam solid dispersion after sieving, controlled slowly releasing adjuncts, filler, 80% correctives and 30% binding agent mix homogeneously;

C, add ethanol/water (30/70) the solution mix homogeneously of residue 70% binding agent, soft material processed;

D, the soft material making is carried out to wet granulation, dry 1 hour granulate for 60 ℃;

E, to the correctives mix homogeneously that adds lubricant and residue 20% in the granule making;

F, tabletting, obtain finished product.