The pharmaceutical composition of regulating metabolic processes, and the method of its production

 

(57) Abstract:

The invention can be used in medicine to treat rheumatism, rheumatic inflammatory diseases, diseases of Edison, acute insufficiency of the adrenal cortex and other Pharmaceutical composition contains an effective amount of prednisolone and pharmaceutically acceptable auxiliary substances: glucose or sucrose, starch, stearic acid and/or its salt. The mass ratio of these auxiliary substances, respectively 1 : 1,12 - 1,77 : 0,003 - 0,03. The mass ratio prednisolone : glucose or sucrose is 1 : 6,8 - 72,0. The composition may be in the form of tablets. A method of obtaining a composition involves mixing prednisone with auxiliary components, moistening the mixture, wet granulation, drying, dry granulation, the powder pellets and molding. The dusting granules carried out with a mixture of starch, stearic acid and/or its salts, when the mass ratio of the components of this mixture 1 : (0,01 - 0,09). The amount of starch for dusting equal to 10.5 - 19,0% of its content in the composition. The composition is stable for at least 2 years. Its composition ensures quick release of prednisolone from the dosage form. 2 C. mA, rheumatic inflammatory diseases, diseases of Edison, acute insufficiency of the adrenal cortex, bronchial asthma, acute and chronic allergic diseases, hepatitis, hepatic coma, hypoglycemic conditions, diseases of the kidneys, the blood, skin and eye diseases, systemic diseases of connective tissue.

Among the tools that regulate metabolic processes, a prominent place is prednisolone or pregnadien-1,4-triol-11, 17, 21-dione-3,20 [Mashkovsky M. D. Medicines, T. 1, ed. 12-e, M, 1993, S. 670]. The connection is a synthetic analogue of the natural glucocorticosteroid - hydrocortisone and has a pronounced anti-inflammatory and antiallergic effect, possesses antishock and immunosuppressive activity, affect different types of metabolism: it increases the level of glucose in the blood, has catabolic effects, contributes to the redistribution of adipose tissue, causes a delay of sodium ions and water in the body, increases blood pressure, reduces the formation of scar tissue.

Prednisolone, like most substances, medicines, has no ability to direct pelletizing. the to be dosage forms necessary to apply auxiliary substances in quantities the designated pharmaceutical and therapeutic usefulness.

There are various dosage forms containing prednisolone - ointments, gels, aerosols, tablets, solutions for intravenous and others.

In the patent of Russian Federation N 2093185 declared 11.05.94 described ointment containing as active ingredient prednisone. In U.S. patent N 3711602, 1973, described the preparations of prednisolone for local application in the form of lotions, ointments, suppositories.

In the United Kingdom patent N 862376, 1961, described pharmaceutical composition, the closest in composition to offer, which contains prednisolone and auxiliary substances, wt.%:

Prednisolone - 5,7

Aluminum hydroxide (dry) - 5,7

Diphosphate calcium - 52,6

Sucrose - 17,2

Emulsifying agent - 5,7

Stearic acid - 11,4

Stearinovokisly calcium - 1,7

To obtain pellets of the composition are mixed prednisolone, dicalcium phosphate, gel, aluminum hydroxide, stearic acid and emulsifying agent (bovine bile), the mixture is moistened sugar syrup, wet pasta granularit and dried at 60oC. the Dry material is passed through the mesh 20 mesh (hole diameter 0.84 mm), optivault the stearate CB release of the active ingredient. In addition, the total content of stearic acid and its salts (13.1% of the total mass of the tablet) is exceed the limit allowed by the global Fund XI - less than 1%.

The objective of this invention is a solid dosage form of the drug for regulation of metabolic processes, satisfying all the requirements in the pharmaceutical means and sustainable for quite a long time (not less than 2 years), as well as simple, yet technologically advanced way of obtaining that allows you to get a quality product.

This objective is achieved in that the pharmaceutical composition regulating metabolic processes, contains as active ingredient a therapeutically effective amount of prednisolone and as auxiliary substances, glucose or sucrose, starch, stearic acid and/or its salt in the following ratio, wt.h.:

Glucose or sucrose - 1,0

Starch - 1,12-1,77

Stearic acid and/or its salt is 0.003 and 0.03,

when this mass ratio prednisolone and glucose or sucrose is 1: 6,8-72,0 respectively.

The claimed ratio of ingredients is best found experimentally and ASS="ptx2">

The introduction of the glucose or sucrose in the specified proportions to the active ingredient significantly increases the stability of the dosage form during storage, which allows to achieve an acceptable shelf life for new members (over 2 years). Joint use as excipients glucose or sucrose, starch, stearic acid and/or a salt thereof in the inventive shares, provides satisfactory strength rapid release of prednisolone from the dosage form (see drawing, which shows the curve of dissolution of tablets prednisolone, example 1).

Noncompliance found ratios of ingredients does not give you the quality and stability of the composition during storage.

The proposed pharmaceutical composition is in the form of solid dosage forms, preferably in the form of tablets that allows for maximum adaptability subsequent packaging and precision dosing of the active substance. The concentration of active ingredient in a unit dose is defined therapeutic appropriateness and higher dose of prednisolone (15 mg) and may be from 0.5 to 15 mg But these limits are not strictly limityou is on, starch and glucose or sucrose and moistening the mixture, followed by wet granulation, drying, dry granulation and dusting granules. To give a composition of the form of tablets obtained after dusting composition is pressed on a tablet machine. Use upon receipt of the granulate as special additives to the active ingredient a mixture of starch and glucose or sucrose provides good adhesion prednisolone and auxiliary substances, which contributes to a significant increase in strength tablets. In addition, it allows you to use as a granulating liquid water without the addition of binders, which greatly simplifies the process. The dusting granulate mixture of starch and stearic acid and/or its salt in a mass ratio of 1: (0,01-0,09) increases the adhesion between the granules and apadravya mixture, which contributes to further improving the strength of the tablets. The number of input stage dusting starch is 10.5-19.0% of the total weight of the starch contained in the dosage form. The change of this ratio affects the fluid properties of the granules and prevents the normal process of tableting.

The obtained pharmaceutical composition complies with the requirements of the global Fund XI (in appearance, raspadaemosti, dissolution, uniformity of dosage and other factors), stable in storage and has a shelf life of over 2 years.

The invention is illustrated by the following examples (see table).

Example 1. Mix the sifted powders prednisolone (10.0 g), dry potato starch (244,5 g) and sucrose (200,0 g) hydrate 100 g of distilled water, mix to a uniform distribution of moisture, granularit on the unit for the production of granulate through a grid hole diameter 2.5 mm and dried to a residual moisture content of 2-4%. Dry granulation is performed on the device for producing granules of the dry mix through a mesh hole diameter 2 mm, Crushed granular optivault mixture of 43.5 g of potato starch and 1,49 g of stearic acid and the prioritization tool.

The mass ratio prednisolone: sucrose is 1: 20.

Example 2. Mix the sifted powders prednisolone (25,0 g), glucose (170,0 g) and starch (242,6 g). Subsequent operations are performed analogously to example 1, with the difference that as outrivaled agent, a mixture of 56,9 g starch, 3.5 g of stearic acid and 1.44 g of calcium stearate. The obtained tablets (484,5 g) satisfy the requirements of the pharmaceutical agent.

The mass ratio prednisolone: glucose is 1:6,8.

Example 3. Analogously to example 1 receive tablets of of 1.25 g of prednisolone. Total consumption other ingredients: sucrose - 90 g starch - 158,3 g, of which 24,0 g load mixed with stearic acid at the stage of powder, stearic acid - 0.25 was the Release of the tablets that meet the requirements of the pharmaceutical agent is, 242,0

The mass ratio prednisolone: sucrose is 1:72.

Example 4. Analogously to example 1 receive tablets from 5.0 g of prednisolone, 115 g of glucose, 128,55 g of starch (13,55 g powder) and 1.22 g of calcium stearate. The output is 242,5, Tablets meet the requirements of the pharmaceutical agent.

Mass soothes is, is the difference that instead of glucose sucrose is used instead of calcium stearate magnesium stearate.

1. The pharmaceutical composition for regulation of metabolic processes, containing an effective amount of prednisolone and pharmaceutically acceptable excipients, characterized in that as auxiliary substances it contains glucose or sucrose, starch, stearic acid and/or its salt in their mass ratio, respectively 1 : 1,12 - 1,77 : 0,003 - 0,03, and the mass ratio prednisolone : glucose or sucrose is 1 : 6,8 - 72,0.

2. The pharmaceutical composition under item 1, characterized in that it is made in the form of tablets.

3. A method of obtaining a pharmaceutical composition, described in paragraph 1, including mixing prednisolone, starch, glucose or sucrose and moistening the mixture, followed by wet granulation, drying, dry granulation, the powder granules and their formation, with a dusting granules carried out with a mixture of starch, stearic acid and/or its salt in mass mixing ratio of 1 : (0,01 - 0,09), and the amount of starch for dusting 10.5 - 19.0 wt.% from his Sumerians>oC to a residual moisture content of 2 to 4%.

 

Same patents:

The invention relates to solid pharmaceutical compositions containing less than 7 wt.% oil or oily substances, a small dose of the active ingredient insoluble in water and seamless polymeric filler, capable of binding water and having an average particle size greater than 150 microns

The invention relates to medicine, in particular to the production of medical biological preparations, and relates to oral formulations of recombinant human erythropoietin, which is used for the treatment of various forms of anemia

The invention relates to the pharmaceutical industry and may be used as excipients in obtaining various pharmacological and/or nutritional

Drug // 2150937
The invention relates to medicine

The invention relates to the field of medicine and is suitable for the treatment of urinary tract infections (pyelonephritis, cystitis, prostatitis), and also to prevent infections after surgery for the kidneys and urinary tract

The invention relates to the field of medicine and concerns nootropic drugs and method of its production

The invention relates to the pharmaceutical industry, specifically to the dosage form of omeprazole and its preparation

FIELD: medicine, oncology.

SUBSTANCE: invention relates to a method for treatment of chronic lympholeukosis. Method involves intravenous drop and jet administration of antitumor chemopreparations and carrying out the autochemotherapy. At the 1-st and 8-th day of treatment cyclophosphan in the dose 750 mg/m2, vincristine in the dose 1.4 mg/m2 and doxorubicin in the dose 30 mg/m2 incubated with 200 ml of autoblood are administrated to patients. From the 1-st to 14-th day of treatment prednisolone is used every day in the therapeutic dose. The treatment course is repeated in 30-35 days depending on blood indices and patient state. The total treatment of courses is 4-5. Method provides reducing cardiotoxicity of doxorubicin and cumulative toxicity of chemopreparations that allows carrying out administration of antitumor chemopreparations in the full volume to patients of elderly age groups.

EFFECT: improved method for treatment.

1 ex

FIELD: medicine, oncohematology.

SUBSTANCE: the present innovation deals with treating elderly patients with chronic lympholeukosis accompanied with cardiovascular failure. The method deals with applying chemopreparations and cytoprotector. Moreover, 1 wk before the onset of chemotherapeutic therapy one should prescribe preductal at the dosage of 105 mg daily. At this background one should sample blood out of elbow vein at the volume of 200 ml into a vial with glugicir to centrifuge it, isolate plasma, divide into two portions, add into the 1st vial - cyclophosphan 600-800 mg/sq. m, vincristin 1.4 mg/sq. m, into the 2nd vial - adriamycin 50 mg/sq. m to be incubated for 30 min at 37 C and intravenously injected by drops for patients. Simultaneously, the intake of prednisolone should be prescribed at the dosage of 60 mg/sq. m since the 1st d and during the next 5 d and preductal at the dosage of 105 mg daily during a week, and then 2 wk more at the dosage of 60 mg daily. All the procedures should be repeated in above-mentioned sequence 4-6 times. The method enables to decrease toxic manifestations of chemotherapy while applying adequate dosages of cytostatics, anthracycline antibiotics, among them, at no great manifestations of their toxicity due to preductal's cardioprotective action.

EFFECT: higher efficiency of therapy.

1 ex, 5 tbl

FIELD: medicine, neurology.

SUBSTANCE: method involves intravenous administration of autolymphocytes treated with an immunomodulating agent by extracorporal method using cycloferon (250 mg) as an immunomodulating agent. Simultaneously, the following medicinal mixture comprising lidocaine, 100 mg; lidazum, 32 U; dexamethasone, 4 mg; leukinferon, 10 000 U; 40% glucose solution, 4 ml is administrated into interspinal ligaments of spinal column at levels corresponding to thoracal and lumbar enlargements of the spinal cord. The procedure is repeated three times with interval for 48-72 h. Method provides enhancing the effectiveness of lymphostimulation and immunomodulation in cerebrospinal sclerosis. Invention can be used for lymphostimulation and immunomodulation in cerebrospinal sclerosis.

EFFECT: improved method for treatment.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: method involves applying napkin impregnated with medicament to an injured articulation area. The medicament contains hydrocortisone acetate in the amount of 0.4mg/cm2, dimexide - 1.4 mg/cm2 and sodium alginate - 4.1 mg/cm2. The napkins are applied to internal and external side of the articulation for 6 days, changing them in three days.

EFFECT: accelerated treatment course.

FIELD: medicine, otorhinolaryngology.

SUBSTANCE: one should treat deformation in laryngeal and tracheal lumen due to excessive growth of granulation tissue in the sites of their lesions. One should introduce hormonal preparations, moreover, one should apply Diprosan as a hormonal preparation injected once intramucosally at 0.1 ml/sq. cm of granulation tissue, but not more than 0.3 ml.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: method involves probing and rinsing lacrimal canaliculus. Working nozzle of YAG laser is additionally introduced into lacrimal canaliculus to reach medial wall of the lacrimal sac. The working nozzle of laser is taken away from the medial lacrimal sac wall in the reverse direction by 2 mm. Laser radiation treatment is applied in constant wave mode (CW) with power of 2.5 W during 5 s in smoothly moving laser working end from the lacrimal canaliculus. The lacrimal canaliculus is washed with corticosteroids.

EFFECT: enhanced effectiveness of treatment.

FIELD: medicine.

SUBSTANCE: the present innovation includes polychemotherapy and radiation therapy. Moreover, polychemotherapy should be carried out by the following scheme: on the 1st and the 8th d of the first and the third courses it is necessary to introduce doxorubicin, cyclophosphan, vincristine, and since the 1st to the 14th d - procarbazine and prednisolone; moreover, on the 1st and the 8th d of the second and the fourth courses one should introduce doxorubicin, bleomycin, vinblastine, dacarbazine. The method enables to decrease the quantity of late therapeutic complications, improves the results of relapse-free, total tumor-specific survival rate and decreases the number of polychemotherapeutic cycles.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: medicine, dermatology.

SUBSTANCE: it is suggested to apply quingamin in combination with prednisolone. The latter should be prescribed at its average daily dosages, and quingamin daily dosage should be increased for 120-130 mg every 9-11 d beginning from 120-130 mg to reach 450-500 mg/d. Moreover, course dosage of quingamin corresponds to 15-18 mg. The method decreases toxic reactions to quingamin introduction.

EFFECT: higher efficiency of therapy.

1 cl, 1 ex

FIELD: medicine.

SUBSTANCE: by the first variant, one should widen lacrimal point, pass with the probe through inferior lacrimal canaliculus up to the rest into the bone followed by visualization of nasal cavity with endoscope, control for light guide's position should be performed due to diaphanoscopic X-raying via the bone. Burning through osseous tissue of lateral wall in nasal cavity should be fulfilled with laser radiation by developing anastomosis between lacrimal sac and nasal cavity till visualization of light guide in nasal tract. Moreover, lateral wall of nasal cavity should be burned through with a solid-state Nd YAG laser at wave length being 1.44 mcm, impulse energy of 300-440 mJ, impulse frequency 10-20 Hz, impulse duration of 50-150 mcsec. Time for osseous impact corresponds to 0.4-4 min. Intubation of developed anastomosis should be carried out through inferior lacrimal point by withdrawing into nasal cavity with drainage out of silicone as a hollow tube. By the second variant, one should perform visualization of nasal cavity with endoscope followed by burning through bony tissue of lateral wall in nasal cavity with laser radiation. Moreover, light guide's fiber should be applied out of nasal cavity. Burning through should be performed by contact being 3 mm to the front against concha nasalis media in projection of lacrimal fossa with a solid-state Nd YAG laser at wave length being 1.44 mcm at impulse energy of 300-350 mJ, impulse frequency of 10-12 Hz, impulse duration of 50-150 mcsec, time for impact is 0.4-4 min. Then comes passing acutely through inferior lacrimal canaliculus till probe's appearance in developed anastomosis. Then one should fulfill intubation of developed anastomosis through inferior lacrimal point at withdrawing into nasal cavity with drainage out of silicone as a hollow tube. The method enables to achieve permeability of tear-secretion tract at low traumatism and high efficiency in postoperative period at no relapses on closing the anastomosis developed between lacrimal sac and nasal cavity.

EFFECT: higher efficiency of therapy.

2 cl, 2 ex

FIELD: medicine, pharmacy.

SUBSTANCE: treatment involves using the injection solution based on water-soluble prednisolon formulation containing sodium salt and accessory additive. Prednisolon sodium phosphate is used as prednisolon water-soluble formulation, and anhydrous sodium hydrogen phosphate and sodium dihydrogen phosphate dihydrate taken in the ratio = (1.375-1.5):1, respectively, are used as sodium salt, and propylene glycol is used as an additional additive in the following ratio of components, wt.-%: prednisolon sodium phosphate (as measured for prednisolon), 2.5-3.5; anhydrous sodium hydrogen phosphate, 0.045-0.055; sodium dihydrogen phosphate dihydrate, 0.03-0.04; propylene glycol, 12-17, and injection water, the balance, up to 100%. Invention can be used in producing hormonal preparation prednisolon in injection formulation for treatment of rheumatism, infectious nonspecific polyarthritis, bronchial asthma, leukemia and other diseases. Invention provides enhancing stability of prednisolon-containing solution and prolonged storage time.

EFFECT: improved and valuable properties of solution.

3 tbl, 2 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes new tablets with size less 3 mm with sustained-releasing the opioid analgesic drug for 30 min in the amount above 75%. Invention provides opioid for oral intake with taking into account individual necessity of patient due to selection of required amount of mictotablets by dispenser.

EFFECT: valuable properties of tablet, expanded assortment of medicinal formulations of opioid analgesics.

19 cl, 4 tbl, 4 ex

Up!