Rectal suppositories, which has anti-inflammatory and analgesic effect

 

(57) Abstract:

The invention relates to medicine and relates, in particular, pharmacology, namely, rectal suppositories, which has anti-inflammatory and analgesic effect, containing the drug nonsteroidal series - indomethacin and the basis, in the following ratio of components, g on one suppository:

Indometacin 0,05-0,1

Aerosil 0,015

Witepsol W35 0,401-0,416

Witepsol H15 0,9360-0,9709

Castor oil 0,039

Urea 0,00105

Nipazol 0,00045

Tween-80 0,00750

Effect: invention allows to provide a high bioavailability of drug substances by rectal way of its introduction into the body, enhances therapeutic effect of indomethacin, improves its release from the dosage form and the absorption of it in the blood, allows to obtain a stable dispersion system when using small amounts of stabilizers, providing the microbial purity of the drug during storage. table 1.

The invention relates to the field of medicine and is suitable for the manufacture of rectal suppositories for the treatment of inflammatory diseases of the joints different etiologically joint diseases of different etiology remains one of the most important in practical medicine, despite the emergence in the global pharmaceutical market dozens of new antiaritmichesky drugs. Currently, the list of medicines of this group consists of 77 basic products, of which 65 belongs to the category of non-steroidal anti-inflammatory drugs (NSAIDs) [1].

From the group of NSAIDs indomethacin is one of the most active anti-inflammatory drugs. Like all NSAIDs, anti-inflammatory, analgesic and antipyretic effects, but the analgesic effect is more pronounced than that of naproxen and voltaren. The results of experimental and clinical studies have shown that indomethacin is superior in anti-inflammatory activity of acetylsalicylic acid, ibuprofen, naproxen. According to the degree of analgesic activity of indomethacin is also superior to acetylsalicylic acid, phenylbutazone, ortofen [2].

Based indometacin known a number of pharmaceutical compositions. In the application of the Russian Federation No. 95101396 described ointment for the treatment of rheumatic diseases on the basis of indomethacin. In the patent of Russian Federation № 2140258 described hydrophilic pharmaceutical composition having anti-inflammatory action, the proposal of the Russian Federation No. 97104487 described/P>Rectal therapy is increasingly used in medical practice. Dignity rectal administration of medicinal substances is that the substance is absorbed goes directly into the bloodstream, bypassing the gastrointestinal tract. This is very important in the treatment of patients with diseases of the duodenum, stomach, liver and kidneys.

Known rectal suppositories, registered in the Russian Federation by foreign firms Ratiopharm GmbH (Germany) and Berlin-Chemie (Germany) (prototype), which contain as active substance a drug nonsteroidal series - indomethacin. As the basis and auxiliary substances suppositories “Indomethacin-Berlin-Chemie” contain cured fat and corn starch. However, more detailed information about pharmaceutical composition in the patent and scientific literature is not detected. Corn starch is a valuable foodstuffs. Moreover, as an auxiliary substance starch is a good source of food for microorganisms and promotes their growth and reproduction that may affect the quality of the suppositories in terms of microbiological purity”.

The objective of this from esteem, and in the development of affordable rectal suppositories-based drug nonsteroidal series - indometacin, the production of which it is possible to establish in our country.

This task is solved in that rectal suppositories containing drug nonsteroidal series - indomethacin and the basis, according to the invention as a basis containing Aerosil, witepsol W35, witepsol H15, castor oil, urea, nipazol, tween-80 in the following ratio of components, g on one suppository weighing 1.5 g±5%:

Indometacin 0,05-0,1

Aerosil 0,015

Witepsol W35 0,401-0,416

Witepsol H15 0,9360-0,9709

Castor oil 0,039

Urea 0,00105

Nipazol 0,00045

Tween-80 0,00750

Introduction in the proposed suppositories as a fatty basis alloy witepsol W-35 and witepsol N-15 can provide a high bioavailability of drug substances by rectal way of its introduction into the body.

The basis of the entered excipients that enhance therapeutic effect indometacin improve its release from the dosage form and the absorption of it in the blood is Aerosil, castor oil and tween-80. Twin and Aerosil belong to stabiiity. Experimentally chosen combination of tween-80 and Aerosil allows to obtain a stable dispersion system when using small amounts of stabilizers.

In addition, the composition of suppositories entered preservatives, ensuring the safety of the drug is nipazol and urea. Fungicidal effect nipazola against yeast fungi is evident at concentrations of 0.015 and 0.06%. In the present suppositories nipazol is used in the amount of 0.03%. This concentration helps to ensure the microbial purity of the drug during storage.

The technology of manufacture of suppositories is as follows.

Example 1. For manufacturing fundamentals take witepsol W35 (236,2 g) and witepsol H15 (551 g), heated to 60-70C until a homogeneous molten mass. Under stirring impose additional ingredients: castor oil (23,4 g), tween-80 (4.5 g), Aerosil (9.0 g), nipazol (0.27 g) and urea (0,63 g). The mass is stirred, cooled. Separately preparing a suspension concentrate indometacin: mix witepsol W-35 (13.5 g), witepsol N-15 (31,5 g), indomethacin (30 g). Then, carefully mixing the Foundation, poured suspension concentrate indomethacin.

Get 859,5 g suppozitornyj homogeneous mass that the requirements of the pharmaceutical agent.

Example 2. For manufacturing fundamentals take witepsol W35 (198,49 g) and witepsol H15 (463,14 g), heated to 60-70C until a homogeneous molten mass. Under stirring impose additional ingredients: castor oil (21,78 g), tween-80 (4,18 g), Aerosil (of 8.37 g), nipazol (0.25 g) and urea (0,586 g). The mass is stirred, cooled. Separately preparing a suspension concentrate indometacin: mix witepsol W35 (25,35 g), witepsol n (59,16 g), indomethacin (56,34 g). Then, carefully mixing the Foundation, poured suspension concentrate indomethacin.

Get 837,6 g suppozitornyj homogeneous mass, which is served on the molding. Received suppositories are white with a yellowish tint, which meet all the requirements of the pharmaceutical agent.

Studies anti-inflammatory activity suppositories conducted on the traditional model of acute inflammation: swelling of the paws of rats induced by PAF (complete adjuvant's adjuvant). The experiments were carried out on outbred albino male rats weighing 250-300 g

PAF was administered to rats subplantar right paw in a volume of 0.1 ml, the test substance was administered 30 min before the introduction of the PAF. The measurement of the volume of the paw was performed using plethysmometer (Ugo Basile) at 24 h group>

where P is the growth edema;

On - volume feet after the introduction of logogen;

And - the value of the volume of the paws before the introduction of logogen.

The effect of therapeutic effects of substances was evaluated by the degree of inhibition of the inflammatory response compared with control formula

where (o) - treated animals

(K) - untreated animals.

The results suggest that the proposed rectal suppositories have significant anti-inflammatory activity that is equivalent in severity to foreign similar “Indomethacin - Berlin-Chemie” (braking acute paw edema in rats was 61 and 55% of untreated control), see table.

The obtained data give reason to believe the proposed rectal suppositories highly effective drug for the treatment of articular syndromes of different etiology, post-traumatic inflammatory syndrome.

Literature

1. Antiarthritic druds. - The yeafs drug news, 1994, p.374-386.

2. Nasonov E. L., Lebedeva O. C. Nonsteroidal anti-inflammatory drugs: mechanism of action and clinical use in rheumatology. News pharmacy and medicine, so 30, 1, 1990.

Indometacin 0,05-0,1

Aerosil 0,015

Witepsol W35 0,401-0,416

Witepsol H15 0,9360-0,9709

Castor oil 0,039

Urea 0,00105

Nipazol 0,00045

Tween-80 0,00750

 

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EFFECT: higher efficiency of application.

4 ex, 3 tbl

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