The composition is a pharmaceutical form of antiarthrotic means glucosamine hydrochloride for injection

 

(57) Abstract:

The invention relates to the pharmaceutical industry. Active ingredient developed compositions for injection is a drug glucosamine hydrochloride. Dosage form for intramuscular and intra-articular injection consists of two vials a and B. Solution A (ampoule 2 ml) contains 20% glucosamine hydrochloride, 0.5% of anaesthetic substance and a stabilizer. Solution B (ampoule 1 ml) contains 0,6% solution BufferedReader substances. Developed composition maintains stability during production and storage.

The invention relates to the pharmaceutical industry, the production of dosage forms with a specific composition and ratio of the components of the injection solution.

Active ingredient developed composition is a drug - glucosamine hydrochloride with antiarthrotic activity and practically non-toxic [1]. Has the formula:

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On the way to get glucosamine hydrochloride we have obtained the patent of Russian Federation(RU) N 2038095, CL 6 A 61 K 35/60 [2].

We have developed dosage form is allowed for practical application Pharmaceuticaltony the action a little stable, hygroscopic, easily oxidized, especially in the wet state. For its stabilization using sodium chloride two mole to one mole of the substance [1, 4].

The disadvantage of this stabilization is the high content of sodium chloride (about 13%), which leads to an increase irritants in biological tissue for intramuscular or intra-articular introduction of the 20% aqueous solution of the drug.

D-glucosamine hydrochloride is a crystalline drug, non-hygroscopic, stable at normal conditions (room temperature and humidity) and even in aqueous solution.

It is established that D-glucosamine hydrochloride under normal conditions stable in crystalline form and in strongly acidic aqueous solutions at short heating. A solution of glucosamine hydrochloride 20% in water has a pH of 1.2 to 2.5. However, when thermal processing in weakly acidic, neutral and especially in alkaline medium it decomposes. In the latter case it goes into the ground and will quickly become brown in color. This disadvantage does not allow to produce sterile injectable pharmaceutical form of the pure substance is glucosamine hydrochloride in the specified conditions. In addition, injecting the intra-articular) introduction. The solution should have a pH close to the pH of the tissue fluids, neutral or weakly alkaline. Strongly acidic or strongly alkaline solutions may cause necrosis of tissue or hemolysis of the blood.

The aim of the invention is the creation of an injectable dosage form is a sterile solution for intramuscular and intra-articular injection, in which the drug is glucosamine hydrochloride in compositions with other substances stable in the manufacture, storage, and has a physiological tolerability in a certain combination and ratio of components.

This goal is achieved by introducing into the composition of stabilizers and other auxiliary substances, which contribute to the preservation of the active substance, do not affect its stability and facilitate the manufacture of dosage forms.

Example pharmaceutical compositions containing glucosamine hydrochloride solution for injection is given first and is different from the compositions described in the patent (UK Patent GB 2101585 A, INT CL53 C07H 5/06 A 61 K 31/70), which can be mistaken for a prototype [4].

Dosage form for injection: solution of glucosamine hydrochloride 20% of the moat: a solution (2 ml) and solution B (1 ml). The composition has the composition:

Solution:

Glucosamine hydrochloride - 200 g 20,0%

Trimekain - 5 g 0,5%

Sodium metabisulfite - 2.2 g 0,22%

Sodium sulfite 1 g of 0.1%

Water for injection to a total volume of Rest 1000 ml 100%

Solution B:

The Ethylenediamine - 6 g 0,6%

Water for injection to a total volume of Rest 1000 ml 100%

Preparation of solution A. Metabisulfite and sodium sulfite dissolved in water, incubated for 15 h, then add glucosamine hydrochloride, trimekain, mix until dissolved and filtered through filter paper (black ribbon). Then the solution is filtered through a membrane filter for sterilizing filter with a pore diameter of 0.1 ám. The solution is poured into vials syringe filling 2 ml) and sealed in a stream of nitrogen and sterilized at 100^oC 30 min to Get a clear solution is slightly yellow.

Preparation of solution B. Ethylenediamine (liquid) is weighed, dissolved in water and filtered through a membrane filter for sterilizing filter with a pore diameter of 0.1 ám. The solution is poured into ampoules in a vacuum filling machine (or other) and 1 ml, sealed under normal conditions and sterilized at 100^oC 30 minutes Obtain a colorless transparent solution.

oC 30 minutes, Re-check the absence of mechanical impurities, mark, check the sterility and apyrogenicity. Packed in sets equal to the number of vials of solutions a and B.

The presence of two capsules in the dosage form is due to the fact that the original 20% solution And is highly acidic (pH of 1.2 to 2.5), in which it can be sterilized without degradation 30 minutes

Metabisulfite and sodium sulfite play the role of stabilizer. However, the solution does not have physiological compatibility with this pH-value and can cause necrosis of tissue for intramuscular or intra-articular injections. To achieve physiologically portable pH values (6,0-6,8), to the solution And attached superyoshi solution B (Ethylenediamine with pH 10,5-11,5). Both solution are mixed in the syringe immediately before injection. Through a needle trying to enter the solution, then the solution B. Temporary local anesthesia provides trimekain. Nitrogen, displacing the air that plays the role of an inert filler and prevents the oxidation of glucosamine hydrochloride in the sterilization and storage.

Injection solution used for intramuscular or intraarticular injection with arthritis according to the instructions.

If the tion. Hrcw. Publishing house "Basis when Haruka sovereign Unversity. - 1992, S. 84-106.

2. The patent of Russian Federation (RU) N 2038095, A 61 K 35/60.

3. The solution FC study of the Russian Federation on the recommendation to the medical use of glucosamine hydrochloride - drug developed Pyatigorsk state Academy and JSC "Sevrybtekhcentr" and JSC "Sevryba", Protocol No. 14 dated July 16, 1995 //Information about the decisions study of the pharmacological Committee of the Russian Federation: New drugs. M., 1995, vol. 5. - S. 54-55, (ISSN 0132-8603).

4.UK Patent GB 2 101 585 A,INT CL53 C 07 H 5/06 A 61 K 31/70.

1 Dosage form antiarthrotic means in the form of a composition of two sterile solutions of substances in water for injection, which are mixed before use, wherein the first solution contains the active substance is glucosamine hydrochloride, and optionally trimekain as an anesthetic, sodium sulfite and sodium metabisulfite as a preservative and antioxidant, and the second solution B contains Ethylenediamine in an amount to provide a pH of 6.0 to 6.8 after mixing the solutions, with the following content of components, mg: 1 a solution: 3 Glucosamine hydrochloride 7 400,0 3 Trimekain 7 10,0 3 Sodium metabisulfite 7 4,4 3 Sodium su the La injection 7 Rest to a total volume of 1 ml