Pharmaceutical composition having analgesic, anti-inflammatory, antipyretic and antispasmodic effect

 

(57) Abstract:

The invention relates to medicine and medical industry and relates to a pharmaceutical composition having analgesic, anti-inflammatory, antipyretic, antispasmodic effect. The invention lies in the fact that the pharmaceutical composition contains as active substances therapeutically effective amount of Metamizole sodium, drotaverine hydrochloride, fenpiveriniya bromide, pitofenone hydrochloride as auxiliary substances, potato starch, lactose, polyvinylpyrrolidone, magnesium stearate. The pharmaceutical composition is in the form of tablets or capsules, a tablet may be coated. The invention provides wide opportunities for the use of the drug in the drug therapy in different fields of medicine, can reduce side effects such as atropine and papaverine. The drug is a strong spasmolysant and analgesic without drugs and its application does not lead to addiction to the drug, the toxicity of the drug is minimized, due to the effectiveness of the preparation period of its use is much reduced and is eenie relates to medicine and the medical industry and for the pharmaceutical composition, analgesic, anti-inflammatory, antipyretic, antispasmodic effect.

Currently known a number of drugs used for stomach cramps and bowel, spastic constipation, stroke and chronic kidney stones, peptic ulcer of stomach and duodenum, which is part of drotaverine hydrochloride - 1-(3,4-diethoxyaniline)-6,7-diethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (tablets of Drotaverine hydrochloride, shpy, NTSh-Bry; combined drugs Nikoshpana, Bispan etc. , M. D. Mashkovsky "Drugs", Moscow, Izd-vo Medicine, so 1, C. 516). However, they have a mild antihypertensive effect and are usually used in combination with other agents.

There are a number of combined drugs with pronounced analgesic, anti-inflammatory and antipyretic properties, which include Metamizole sodium - 1-phenyl-2,3-dimethyl-4-methylaminophenol-5-N-methanesulfonate sodium tablets Aapirin, "Benalgin", Tempalgin etc., M. D. Mashkovsky "Drugs", Moscow, Izd-vo Medicine, so 1, S. 201), relieving pain, spasm of smooth muscles: renal colic, Ableton. One tablet contains metamizol sodium 0.5 g, fenpiveriniya bromide 0.0001 g, pitofenone hydrochloride 0,005 g ("Register of medicines, electronic version 2000) the Disadvantage of this drug is its low therapeutic activity when removing spasms of smooth muscles and the necessity of combining with other drugs.

Great therapeutic value have a combination of drugs, which include several active substances, which patentiert the action of each other, complexly affecting the body.

Known drug "Kvareli" manufactured by "Chinon", Hungary, one tablet which contains metamizol sodium 0.4 g of drotaverine hydrochloride and 0.04 g of caffeine is 0.06, ("Register of medicines, electronic version 2000 ), with analgesic, antipyretic protivomigrenoznami, stimulating, antispasmodic effect (prototype). The disadvantage of this tool is the content in its composition caffeine, which provides a stimulating effect on the Central nervous system, it is contraindicated in people with diseases of the cardiovascular system in old age.

Hereby, the image is of bleak or capsules, with a wide range of therapeutic actions: analgesic, anti-inflammatory, antipyretic, antispasmodic, satisfying all the requirements in the pharmaceutical means and sustainable in the long time storage (not less than 3 years).

This objective is achieved in that the pharmaceutical composition contains as active substances therapeutically effective amount of Metamizole sodium, drotaverine hydrochloride, Geneve-riniya bromide, pitofenone hydrochloride as auxiliary substances, potato starch, lactose, polyvinylpyrrolidone, magnesium stearate in the following ratio, wt.%:

Metamizole sodium - 67-79

Of drotaverine hydrochloride, 5-13,5

Fenpiveriniya bromide - 0-0,016

Pitofenona hydrochloride - 0-0,8

Lactose - 4,6-5,0

Polyvinylpyrrolidone - 1-2

Magnesium stearate 0.5 to 1.2

Potato starch - Rest

Metamizole sodium - strong Central non-narcotic analgesic, which relieves pain of different origin and in spastic conditions increases the effect produced by inflammatory components. Metamizole sodium has a very low toxicity have it bio-transformed into 4-aminophenazone (22,6%), 4-acetylaminophenol (27,5%) and in small quantities - in rubazonovaya acid. All of the above decomposition products stand out from the patient's body along with urine.

Characteristics to non-narcotic analgesics are:

- analgesic activity, which is manifested in certain types of pain: mainly in nerve, muscle, and joint pain, headache and toothache;

- antipyretic effect, resulting in febrile States;

- no depressive effect on the respiratory and cough centres;

- lack in their application of euphoria and mental phenomena and physical dependence.

Metamizole sodium synergize the action antispasmodic components.

Drotaverine lowers tone and reduces contractile activity of smooth muscles and has therefore a vasodilator and antispasmodic action. Effect on the Central nervous system are not only in large doses, it has some sedative effect. Drotaverine is widely used as a spasmolytic agent with stomach cramps and bowel, spastic constipation, stroke and chronic kidney stone SS="ptx2">

Fenpiveriniya bromide is a typical representative neurotrophic antispasmodics, which act like atropine, but without its side effects. Parasympathetic action fenpiveriniya bromide is based on the ousting of acetylcholine, it blocks the transmission of impulses in peripheral parasympathetic nervous branching smooth muscle. Has the same effect as phagotrophy ganglioplegic blockade of parasympathetic ganglia.

Pitofenona hydrochloride belongs to a group musculotropic antispasmodics with sustainable effect. His grasp directly the smooth muscle cells, which means that it stops the spasms of smooth muscles, regardless of their innervation. In addition to clearly defined musculotropic effect pitofenona hydrochloride has soft neurotrophin (parasympathetic) and antihistamine effect: as a result, only one this substance enables you to get neuromuscularly spasmolytic effect.

The composition and the quantitative content of the active ingredients and auxiliary substances established in the research (the study of acute and subacute toxicity of drugs, their specific activity on a painkiller antipolitician experimentally and provides the required quality of the composition.

Upon receipt of the combined drug, analgesic, anti-inflammatory, antipyretic, antispasmodic effect, use the typical equipment used in the chemical-pharmaceutical plant (crushers; vibrating screens; equipment for production of granules by wet granulation followed by drying and dry granulation or installation to obtain granules in the fluidized bed; mixers; tablet presses; machines for filling capsules; installations for the coating of tablets in the fluidized bed or drazherovalnogo boiler; packaging machines).

Method of producing solid dosage forms is:

in sifting ingredients;

- mixing the active ingredients with excipients (lactose, starch);

- granulation mixture of starch paste and solution of polyvinylpyrrolidone;

- drying of the granules, screening, dusting granulate sliding;

The obtained granulate can be used to produce solid dosage forms such as tablets or filling of hard gelatin capsules.

When necessary, the solid dosage form tablet is the pharmaceutical composition having anti-inflammatory, antipyretic, analgesic, antispasmodic effect, contains as active ingredients analgin (Metamizole sodium) and drotaverine, or dipyrone and drotaverine and pitofenone hydrochloride, or dipyrone and drotaverine and fenpiveriniya bromide, further comprises excipients - potato starch, lactose, polyvinylpyrrolidone, magnesium stearate, the amount of which varies from 10 to 23% of the total mass of the drug.

The inclusion of a medicinal product of several active substances has the following advantages:

a) a carefully selected composition of antispasmodics and potent analgesic opens wide possibilities for the use of the drug in the drug therapy in different fields of medicine;

b) the synergistic action of the individual components can reduce the dosage and thereby reduce the side effects as atropine and papaverine;

C) the drug is a strong spasmolysant and analgesic without drugs and its application does not lead to addiction to the medication;

g) the toxicity of the drug is reduced to a mini is desirable effects on blood picture (granulocytopenia).

The composition and quantity of auxiliary substances are optimal and determined experimentally, provide necessary quality of the composition and its stability.

Reducing the number of auxiliary substances leads to deterioration of the quality of tablets/capsules (increase time raspadaemosti, deterioration test "Dissolution", cementing tablets during storage (product will not withstand the required retention period).

Improving auxiliary substances about 23% impractical because it is undesirable that the intake of the patient "extra", although indifferent substances.

As a binder, moving and loosening substances used potato starch, the amount of which was found experimentally. Main criteria for selection of the amount of starch were pharmaceutical (ensuring quality indicators - in particular, raspadaemosti, strength, etc.) and therapeutic (decrease side effects active ingredients - analgin, drotaverine on the gastrointestinal tract) expediency.

The use of milk sugar (lactose) in the claimed amount can increase the release of active substances olnine capsules).

The inclusion of polyvinylpyrrolidone in the composition caused by the necessity of obtaining the drug with the good results of dissolution, raspadaemosti, strength and stability during storage.

To give tableting mass sufficient for the industrial production of antifriction properties used magnesium stearate. The number determined experimentally, is 0.5 - 1.2% of the total mass. Reduced levels of magnesium stearate below 0.5% leads to deterioration of the tabletting process (filling of capsules, tablets turn out rough, jagged edges, there is a sticky mass on the punch press and the lifters machine, poorly kept hanging.

Increasing magnesium stearate more than 1-1,2% does not improve the technological characteristics of the mass.

Qualitative and quantitative composition provides sustained therapeutic effect without toxic effects on humans.

The invention is illustrated by the following examples.

Example 1.

In the installation of fluidized bed type "Glatt" or "Aromatic" download 265 g Metamizole sodium, 40 g of drotaverine hydrochloride, 16,94 g of lactose, 23,23 g of potato starch and thoroughly peripherality and 2% starch paste. The obtained granulate is dried, optivault of magnesium stearate and tabletirujut.

Get tablets with an average weight 0,665 - 0,7-0,735, Strength tablets 120-140 N, the abrasion resistance is not less than 99,5%.

The finished tablets are covered with a shell-based hydroxypropylmethylcellulose in the fluidized bed in the installation "Glatt" or "Aromatic" or boiler for sugar coating or film membrane (GS, ERWEKA).

Example 2.

In the installation of fluidized bed type "Glatt" or "Aroma-tick" load 265 g Metamizole sodium, 20 g of drotaverine hydrochloride, 2,54 g pitofenone hydrochloride, 17 g of lactose, 33,43 g of potato starch and mix thoroughly. The mixture is moistened granulating liquid, a mixture of 10% aqueous solution of polyvinylpyrrolidone, and 2% starch paste. The obtained granulate is dried, optivault of magnesium stearate and tabletirujut.

Get tablets with an average weight 0,665 - 0,7-0,735, Strength tablets 120-140 N, abrasion - at least 99.6%.

The finished tablets are covered with a shell-based hydroxypropylmethylcellulose in the fluidized bed in the installation "Glatt" or "Aromatic" or boiler for sugar coating or film Obol is ujaut 265 g Metamizole sodium, 20 g of drotaverine hydrochloride, 0,0525 g fenpiveriniya bromide, 17 g of lactose, 35,9175 g of potato starch and mix thoroughly. The mixture of powders moisturize granulating liquid, a mixture of 10% aqueous solution of polyvinylpyrrolidone, and 2% starch paste. The moist mass is forced through a sieve, dried, hold the dry granulation, optivault of magnesium stearate and tabletirujut.

Get tablets with an average weight 0,665 - 0,7-0,735, Strength tablets 120-140 N, the abrasion resistance is not less than 99, 5%.

The finished tablets are covered with a shell-based hydroxypropylmethylcellulose in the fluidized bed in the installation "Glatt" or "Aromatic" or boiler for sugar coating or film membrane (GS, ERWEKA).

1. Pharmaceutical composition having analgesic, anti-inflammatory, antipyretic, antispasmodic effect and containing active substance, characterized in that as the active substances it contains Metamizole sodium, drotaverine hydrochloride, fenpiveriniya bromide, pitofenone hydrochloride if necessary, and the target additives, lactose, polyvinylpyrrolidone, magnesium stearate, potato starch in the following ratio and the 0-0,016

Pitofenona hydrochloride - 0-0,8

Lactose - 4,6-5,0

Polyvinylpyrrolidone - 1-2

Magnesium stearate 0.5 to 1.2

Potato starch - Rest

2. The pharmaceutical composition under item 1, characterized in that the number of excipients lactose, polyvinylpyrrolidone, magnesium stearate, potato starch ranges from 10 to 23% by weight of the total pharmaceutical composition.

3. The pharmaceutical composition under item 1, characterized in that it is made in the form of solid dosage forms.

4. The pharmaceutical composition under item 1, characterized in that it is made in pill form.

5. The pharmaceutical composition under item 1, characterized in that it is coated.

6. The pharmaceutical composition under item 1, characterized in that it is made in the form of hard gelatin capsules.

 

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