The drug interoir for the treatment and prevention of viral diseases

 

(57) Abstract:

The invention relates to medicine and for the development of new drugs for the treatment and prevention of viral diseases. The drug contains a leukocyte interferon of human and ointment base comprising a polyethylene oxide with a molecular weight of 1500 and water in the following ratio, wt.%: leukocyte interferon of human activity ME in g 3000 5,0, water 19,0, polyethylene oxide 1500 to 100.0. Technical result: the expansion of the means for the treatment and prevention of viral diseases. table 4.

The invention relates to medicine, in particular, to the treatment and prevention of viral diseases. Known ointment containing as active substance genetically engineered human interferon alpha-2, vitamins E and C, and the filler in the following ratio, wt.%.

Genetically engineered interferon Alfa-2 ME - 4000000

Vitamin E (tocopherol) - 25,0-30,0

Vitamin C (ascorbic acid) - 1,5-2,0

Ointment base 100

(C. N 95121623/14, MPK A 61 K 38/21, B. I. N 13, 1998, page 53, similar).

The disadvantage of this drug is that as the active substance used gienskogo actions because it is the product of only one gene and represents a molecule interferon alpha-2 type. Unlike genetically engineered leukocyte interferon produced by human leukocytes human blood in response to the impact of the virus-interferonogene and is a group of proteins with antiviral and immunomodulating effect (interferons, interleukins, factor migration macrophages, tumor necrosis factor and others), which explains its wide use for the prevention and treatment of viral infections of man.

Known interferon for topical application, containing a therapeutically effective amount of one or more interferons (including human leukocyte), the base comprising polyethylene oxide and one or more preservatives to prevent the destruction of the activity of interferon (prototype, EP N 0152345 from 21.08.85 year).

For ointments on the basis of leukocyte interferon of human use in the form of a concentrated aqueous solution with a titer 25000-500000 IU/ml).

15 ml of this solution to take 100 grams of a mixture of 3350 polyethylene oxide and polyethylene oxide 400 in the ratio 2:3. The mixture of oxides is heated to +45

The disadvantages of this drug are:

- the use of interferon human leukocyte with a high titer to provide stock specific activity, as used in the wax-based polyethylene oxide 400 has a large number of open radicals, which can extinguish the biological activity of interferon; in addition, the manufacturing process involves heating of interferon to 45, and that the critical temperature for proteins (on the border of protein denaturation or loss of biological activity);

- introduction of additional chemicals as stabilizers and preservatives (if stored at -20oC drug loses 34% activity within 1-5 months);

the drug has a firm texture and melts at a temperature of +45oC, as a consequence, poorly absorbed, when applying requires certain way appliques;

- finished preparation should be stored at -20oC.

The aim of the invention is the provision of a more convenient method of application and storage of the drug, increase shelf life and reduce the cost due to the use of low titers of interferon human leukocyte.

Perfere human leukocyte and ointment base, including polyethylene oxide with a molecular weight of 1500 and water. The ratio of components, wt.% the following:

Leukocyte interferon of human activity ME in g 3000 - 5,0

Water - 19,0

The polyethylene oxide 1500 - up to 100.0

The polyethylene oxide with a molecular weight of 1500 is included along with water in the composition of the ointment bases and is a white, yellowish or grayish waxy flakes, powder, or solid mass. Molecular weight of from 1400 to 1600. The formula H(O-CH2-CH2)nOH, n=32-36 (FS 42-1885-96).

The drug is prepared as follows.

Interferon human leukocyte dry prepared in accordance with RP N 42-21-95. The polyethylene oxide (PEO)-1500 melted at a temperature (602)oC, cook 80% PEO solution, mixing a portion of the molten PEO-1500 and distilled water. It is an ointment base. Do the calculation and prepare sample interferon human leukocyte dry and ointment bases, based on the ratio of interferon - 5%, ointment bases - 95%. In a sterile bowl mix interferon and ointment base with a magnetic stirrer. The rotation speed of the stirrer (10010) rpm, mixing time is 30 minutes. Using dosing syringe type ointment, repaso with a grayish tint, thick consistency, is water soluble and melts at human body temperature (35-37)oC.

To determine the optimum ratio of water and polyethylene oxide 1500 in the ointment base were made of 5 mixtures with different content of these components (see table. 1).

From table. 1 shows that the optimal is the following ratio of components in 100 g ointment: water - 20; polyethylene oxide 1500 - 80. In addition, the ointment base with the same ratio of components, unlike others, does not change the physical properties during storage at a temperature of (4-8)oC (storage temperature interferon human leukocyte dry).

To test for curative and preventive action the proposed drug and the optimal content of the active substance were made 3 variants of the mixture components with the following content leukocyte interferon human, wt. % 3,0; 5,0; 7.0 (ointment "Interoir" respectively 3%; 5%; 7%).

As in the description of the prototype, no information about therapeutic effect of the drug, the authors decided to compare the two dosage forms interferon-based human leukocyte - ointment and native.

The study included 77 children, divided into 5 groups: the children of the first group (12 persons) received 3% "Interoir"; the second (23) - - 5% "Interoir"; the third (18 people) - 7% "Interoir"; the fourth (10 people) - native interferon, children of the fifth group (14 people) with the same disease has been usual for these clinical forms of treatment and served as a comparison group (control) in assessing the effectiveness interferonoterapii in normal and ointment form.

"Enterovirus" smeared each nostril in the first 3 days three through 4-6 hours, then twice in 6 hours. Native interferon was used in accordance with instructions for use of interferon human leukocyte dry.

The treatment of sick children "Enterovirus" reduced recovery time compared with the control group: 3% "Interoir" - 4.9 days, 5% - 8.6 days, 7% - 8.4 days; treatment of native interferon - 8.1 days if the average duration of disease in the control group 14.6 days (see table. 2).

Thus interferon human leukocyte in ointment form for therapeutic efficacy was not inferior interferon human leukocyte dry.

"Interoir" 5 the Eden research has shown, the content in the inventive preparation of leukocyte interferon human in an amount of 5 wt.% (5% ointment "Interoir") is optimal.

Tolerability of drug treatment "Interoir good, the General and local side effects of the drug was absent.

In the pediatric ward No. 1 medical-sanitary unit, Tomsk was also conducted work on the study of prevention of drug action "Interoir" at a time when there outbreaks of ARD.

The study included 3 groups of children: the first 30 children, the second 23 children, the third of 27 children. As of the date of application of preparations of interferon (5% "Interoir and native interferon), i.e., in the early days of outbreaks of acute respiratory infections among children in the first group ill 11 children (37.7 per cent), from the second group of 9 children (39%) (see table. 3).

The remaining 19 children of the first group, the former in contact with infected appointed 5% "Interoir", 14 children from the second group of native interferon. Interferon preparations were applied intranasally 2 times a day at intervals of not less than 6 hours within 6 days from the last reported case ARD or isolation of the last patient. The monitoring was conducted for a period of not less than 12 days from the beginning of their application.

This allowed the (control) group, where children had not received interferon, ill 70.3% of children. Compared with this group, the performance index in the first two were, respectively, 4.4 and 3.3V. The performance index "Interavia" compared with native interferon was 1.3.

Thus, the claimed drug compared with native interferon-allows you to roll over a specific effect of interferon human leukocyte due to more complete utilization and, consequently, reduce the frequency of daily use of the drug in the same positive effect.

Monitoring the specific activity of the drug "Interoir" during storage at a temperature of 4-8oC showed that the drug retained its activity for 6 months and only after 7 months of its activity decreased (see table. 4).

Thus the claimed product has a plastic consistency that melts at body temperature, it is quickly absorbed, does not require additional devices for the application is stored at a temperature of 4-8oC (in terms of household refrigerator). The drug long enough retains specific activity (6 months) and does not require the introduction by the drug cheaper due to more simple methods of manufacture and use of interferon human leukocyte smaller titles on 1 g of the drug.

Currently released 15 experimental series of the proposed drug "Interoir" and it is developed regulatory documents.

Drug for the treatment and prophylaxis of viral diseases, containing leukocyte interferon of human and ointment base comprising polyethylene oxide, characterized in that as ointment bases contains a polyethylene oxide with a molecular weight of 1500 and water in the following ratio, wt.%:

Leukocyte interferon of human activity IU g 3000 - 5,0

Water - 19,0

The Polyethylene Oxide 1500 - Up To 100.0

 

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FIELD: medicine, anesthesiology-resuscitation, infectology, detoxication.

SUBSTANCE: the innovation suggested interrupts infectious-toxic shock, moreover, after that it is necessary to prescribe peroral intake of Reaferon-EC-Lipint at the dosage of 10000 - 15000 U/kg. Then one should sample patient's blood to obtain leukocytes to be washed and diluted in 0.9%-NaCl solution, activated due to incubation with immunophan and intravenously injected for a patient. Then comes peroral intake of Reaferon-EC-Lipint at the dosage of 10000 - 15000 U/kg once daily for 5 d. The innovation enables to decrease the number of complications and lethality due to decreasing immunodeficiency.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

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