The method of obtaining the dosage form of high molecular weight polyethylene oxide

 

(57) Abstract:

The method is intended for use in medicine received the dosage form for intravenous administration. Powder of polyethylene oxide with a molecular mass of more than 1 million D is dissolved in a glucose solution. The mass ratio of the polyethylene oxide: glucose - 1:25-1:50. After dissolution spend sterilizing filtration and lyophilization, sterile solution. table 2.

The invention relates to medicine, in particular to pharmacology.

Known properties of PEO with molecular weight of 105-107D. to show the Toms effect when added to the fluid at a concentration of 10-6-10-5g/ml and lower hydrodynamic resistance in conditions of turbulent flow [1, 2]. However, the application of ROA in medical practice it is impossible in the absence of the dosage form for intravenous administration. Difficulties in obtaining medicinal forms PEO are associated with a low rate of dissolution of the substance in water [3, 4] and instability in aqueous solutions [5].

The technical task of the present invention is to develop soluble in water or physiological solution dosage forms of high molecular weight PEO for inside with a molecular mass of more than 1 million D in glucose solution at a ratio of 1: 25-1: 50 (PEO:glucose ) with further sterilizing filtration and lyophilization. The rapid solubility of this drug form and the lack of differences in activity compared to the starting material shown in examples 1-4.

Example 1. Prepare 0,2% solution of PEO powder PEO with molecular weight 51106L of distilled water in accordance with THE 6-58-340-89 [6] . For this sample PEO by weight of 2 g pour a thin stream into the vessel with 1 l of water while stirring with a stirrer at 60 rpm After swelling particles PEO solution is stirred until complete dissolution. The solution is sterilized by filtration in accordance with the requirements of the State Pharmacopoeia X1 [7] . A sterile solution of PEO poured into sterile vials type FD-10 (5 ml) and subjected to freeze drying. For storage preparation after drying, the vials are closed with sterile rubber stoppers and compresses aluminum caps.

Test the solubility is carried out after adding in a bottle of 10 ml water for injection. The contents of the vial are mixed by inversion and monitor the completeness of the dissolution of the PEO. The results are given in table. 1. The time of dissolution sterilin the phenomenon of the Toms effect. The contents of the vial after the complete dissolution of PEO (10 ml 0.1% solution of PEO) is transferred into a volumetric flask of 1 l and adjusted with distilled water to the mark. 200 ml of the obtained solution of PEO (10-5g/ml) expanded through a capillary in the turbulent regime [8]. Experience repeat 3-4 times. The results of the tests are presented in table. 2. To control the flow through the capillary of distilled water was 9,920,08; time flow through the capillary of the PEO solution was 8,400,08 C.

Thus, sterilizing filtration does not alter the properties of PEO (retained the ability to show the Toms effect), but does not increase the rate of dissolution of the substance in water.

Example 2. Prepare 0,2% solution of PEO powder PEO with molecular weight 51106D. on 2% glucose solution in accordance with THE 6-58-340-89 [6]. For this sample PEO by weight of 2 g pour a thin stream into the vessel with 1 l of 2% glucose solution while stirring with a stirrer at 60 rpm After swelling particles PEO solution is stirred until complete dissolution. The solution is sterilized by filtration in accordance with the requirements of the State Pharmacopoeia X1 [7]. A sterile solution of PEO poured into sterile vials type FD-10 to 5 ml is more sterile rubber stoppers and compresses aluminum caps.

Test the solubility is carried out after adding in a bottle of 10 ml water for injection or sterile saline. The contents of the vial are mixed by inversion and monitor the completeness of the dissolution of the dried mixture. The results are given in table. 1. The time of the dissolution of sterile lyophilized mixture of PEO and glucose in water at physiological NaCl solution, respectively 3,70,3 and 3,50,2 minutes

Test conduct Toms effect. The contents of the vial after complete dissolution of the freeze-dried mixture of PEO and glucose (10 ml 0.1% solution of PEO) is transferred into a volumetric flask of 1 l and adjusted with distilled water to the mark. 200 ml of the obtained solution of PEO (10-5/g/ml) expanded through a capillary in the turbulent regime [8]. Experience repeat 3-4 times. The results of the tests are presented in table. 2. To control the flow through the capillary of distilled water was 9,920,08; time flow through the capillary solution lyophilized mixture was 8,370,05 C.

Example 3. Prepare 0,2% solution of PEO powder PEO with molecular weight 51106D. on 5% glucose solution in accordance with THE 6-58-340-99 [6]. For this sample PEO by weight of 2 g up drying the N. After swelling particles PEO solution is stirred until complete dissolution. The solution is sterilized by filtration in accordance with the requirements of the State Pharmacopoeia X1 [7]. A sterile solution of PEO poured into sterile vials type FD-10 (5 ml) and subjected to freeze drying. To store liofilizirovannoe mixture of PEO and glucose after drying, the vials are closed with sterile rubber stoppers and compresses aluminum caps.

Test the solubility is carried out after adding in a bottle of 10 ml water for injection or sterile saline. The contents of the vial are mixed by inversion and monitor the completeness of the dissolution of the dried mixture. The results are given in table. 1. The time of the dissolution of sterile lyophilized mixture of PEO and glucose in water and saline solution, respectively 2,10,2 and 2,20,3 minutes

Test the effect of Toms. The contents of the vial after complete dissolution of the freeze-dried mixture of PEO and glucose (10 ml 0.1% solution of PEO) is transferred into a volumetric flask of 1 l and adjusted with distilled water to the mark. 200 ml of the obtained solution of PEO (10-5g/ml) expanded through a capillary in the turbulent regime in the us is ez capillary distilled water was 9,920,08; the time of flow through the capillary solution dried I was 8,380,07 C.

Example 4. Prepare a 0.2% solution of PEO powder PEO with molecular weight 51106D. on 10% glucose solution in accordance with THE 6-58-340-89 [6]. For this sample PEO by weight of 2 g pour a thin stream into the vessel with 1 l of 5% glucose solution while stirring with a stirrer at 60 rpm After swelling particles PEO solution is stirred until complete dissolution. The solution is sterilized by filtration in accordance with the requirements of the State Pharmacopoeia X1 [7]. A sterile solution of PEO poured into sterile vials type FD-10 (5 ml) and subjected to freeze drying. To store dried mixture of PEO and glucose after drying, the vials are closed with sterile rubber stoppers and compresses aluminum caps.

Test the solubility is carried out after adding in a bottle of 10 ml water for injection or sterile saline. The contents of the vial are mixed by inversion and monitor the completeness of the dissolution of the dried mixture. The results are given in table. 1. The time of the dissolution of sterile lyophilized mixture of PEO and glucose in water and physiological races of the e bottle after complete dissolution of the freeze-dried mixture of PEO and glucose (10 ml 0.1% solution of PEO) is transferred into a volumetric flask of 1 l and adjusted with distilled water to the mark. 200 ml of the obtained solution of PEO (10-5g/ml) expanded through a capillary in the turbulent regime [8]. Experience repeat 3-4 times. The results of the tests are presented in table. 2. To control the flow through the capillary of distilled water was 9,920,08; time flow through the capillary solution lyophilized mixture was 8,400,10 C.

Thus, sterile filtration and lyophilization of a solution of PEO with glucose does not alter the properties of PEO (retains the ability to exercise the Toms effect). Lyophilized mixture of PEO with molecular weight 51106D and glucose in the ratio 1: 10, 1:25 and 1:50 has the properties of bystrorastvorimoi. The rate of dissolution of freeze-dried mixture of PEO and glucose in the ratio 1:25 and 1:50 is higher than the freeze-dried mixture of PEO and glucose in the ratio 1:10.

Quick-dissolving dosage form for intravenous administration of high molecular weight PEO can be used:

1) to stabilize hemodynamics during infusion therapy blood loss and shock as a means of "substitutive therapy;

2) to reduce hemolysis of erythrocytes in the extracorporeal circulation apparatus for implanting an artificial valves CE the system exclusive hemodynamics in hypertensive disease;

4) to improve blood flow and weakening regional ischemia in conditions of stenosis of blood vessels.

Sources of information

1. Patent 3590124 USA, NRI 424-78. Blood transfusion fluids having reduced terbulent fraction properties. Publ. 29.06.71.

2. Grigoryan, S. C. , Gannushkina I. C., Kameneva, M. V. and others // the Mechanisms of the biological continuum. - M., 1986. - S. 75-88.

3. Polimeni P. I., Ottenbreit C. T. // J. Cardiovasc. Pharmacol. - 1989. - Vol. 14. - P. 374-380.

4. Unthank J. L., S. G. Lalka, Nixon J. C., A. Sawchuk, P. // J. Surg. Res. - 1992. - Vol. 53, N 6. - P. 625-630.

5. Little R. C. //Ind. Eng. Chem. Fund. - 1969. - Vol. 8, N 3. - P. 557-559.

6. The polyethylene oxide 1660. Technical conditions. THE 6-58-340-99.

7. State Pharmacopoeia of the USSR. - M., 1990. - X1 ed., vol. 2. - S. 23-24.

8. Grigoryan, S. C., Gannushkina I. C. M. Kamenev Century. etc. // Anestesiol. and Reanimator. - 1987. - #4. - S. 64-66.

The method of obtaining the dosage form of high molecular weight polyethylene oxide, consisting in dissolving polyethylene oxide, wherein the silica powder of polyethylene oxide produced in the glucose solution in the ratio of 1 : 25 - 1 : 50 (polyethyleneoxide : glucose), as high molecular weight polyethylene oxide is used a polyethylene oxide with a molecular mass of more than 1 million D, after dissolution is carried out by STERI

 

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