Medicinal gel

 

(57) Abstract:

The invention relates to medicine and the pharmaceutical industry and relates to dosage forms containing interferon. The essence of the invention: a gel with interferon and vitamin E, contains additional methionine, benzoic acid, citric acid, albumin human serum, ethyl alcohol, glycerin, sodium carboxymethylcellulose, sodium tetraborate and water. Technical result: the gel has several advantages: a wider range of therapeutic applications, a higher degree of antiviral activity in comparison with the prototype when equal doses of interferon, greater efficiency; the drug causes no side effects, easy to use. 3 table.

The invention relates to medicine and the pharmaceutical industry and relates to dosage forms containing interferon.

Well-known domestic genetically engineered human interferon alpha-2 (MF -2), which has a pronounced biological activity in cultured human cells [1] . For clinical purposes in the Russian Federation issued several dosage forms of the drug: intranasal (ME 100 vials), and the drug form (trade name "VIFERON") unlike other drugs interferon additionally contains a complex of vitamins, antioxidants E and C. A logical continuation of this drug became the ointment "VIFERON", which is the same as in candles, in addition to the main active substance is a genetically engineered human IGF-2 - there are vitamins E and C [7].

Disadvantages ointments due to the hydrophobic nature of the fatty basis. First of all, it can result in difficulties in bioavailability, because hydrophobic the basis of the flow of matter occurs only from the layer of ointment, which is in direct contact with the skin. Hydrophobic ointment interferes with the normal gas exchange and thus violates the skin to breathe. Furthermore, the hydrophobic base makes contact with mucous membranes, so the application of ointments with fatty bases on the mucous does not give high effect.

Known gel-based leukocyte interferon containing interferon and adequate pharmaceutical carrier (EP 0127130 AND 61 TO 45/02). However, the range of its application is limited because the product contains only one active substance.

The essence of the invention lies in the fact that the proposed medicinal gel with interferon alpha-2 and a complex of antioxidants, contains, wt%:

Genetically engineered interferon Alfa-2, thousand IU/ml - 5 - 500

Ethyl - 1 - 10

Glycerol - 2 - 20

Sodium carboxymethylcellulose - 0,5 - 2,5

Sodium tetraborate - 0,1 - 1,0

Water Up to 100.0 h

Essential features of the invention is the inclusion in the composition of the complex of antioxidants of different mechanism of action. Antioxidants stabilize the membranes of cells, increasing their resistance to different damaging agents (infectious agents, ionizing radiation, toxic substances). As included in the gel antioxidants act at different stages of the process of free radical oxidation, their combined use provides for the full protection of the cells from the damaging effects of intermediate and final products of lipid peroxidation. Tocopherol possesses direct anti-radical action, methionine and benzoic acid neutralizing hydroxyl radicals, citric acid binds ions of metals of variable valency, which initiate the peroxidation processes. In laboratory experiments it was shown that in case of joint registration in cell culture interferon and antioxidants antiviral activity of interferon increases synergize. Property interferon is raised by the introduction in the preparation of benzoic acid and sodium tetraborate, which have direct antimicrobial activity. Thus, the introduction to dosage form of interferon complex of antioxidants and antibacterial substances allows to obtain a new result, namely:

1) to expand the range of therapeutic applications, using gel with antioxidants when those entities when applying gel only with interferon little or ineffective;

2) to achieve the same level of antiviral activity, as the gel-prototype with reduced dose of interferon (either to obtain higher efficiency at the same dose interferon);

3) to avoid side effects, inherent to the interferon, due to the correction by antioxidants.

In special analyses it has been shown that going beyond the stated values of the components of the gel reduction causes a decrease in specific activity, and increase leads to a deterioration of the organoleptic properties of the gel without amplification of specific activity.

Below is a description of the components in the gel:

Recombinant alpha-2 interferon

Is produced by a bacterial strain found in the genetic equipment is momu interferon. Porous powder or porous mass of white, hygroscopic. It has antiviral, immunomodulatory and antitumor activity. Apply with viral and malignant diseases. Assign intramuscularly, subkonyunktivalno and topically (as eye drops).

Tocopherol acetate (Vitamin E)

Light yellow transparent viscous oily liquid with a faint odor. The oxidized light and dark. Is a natural antioxidant (antioxidant direct action). Participates in the biosynthesis of heme and proteins, cell proliferation, tissue respiration, and other critical processes of cellular metabolism.

Methionine

White crystalline powder with a characteristic odor (merkaptosoedineny) and slightly sweet taste. It is soluble in water. Is one of the essential amino acids needed to sustain growth and nitrogen balance of the body. Involved in the synthesis of adrenaline, creatine and other biologically important compounds; activates the action of hormones, vitamins, enzymes. By methylation and transsylvania methionine neutralizes toxic products. Possesses antioxidant activity due to inactivation for the chronic alcoholism, diabetes and other

Benzoic acid

Bezenye needle crystals or white crystalline powder. Little soluble in water. Possesses antioxidant activity due to inactivation of hydroxyl radicals. It is used externally as an antimicrobial and fungicidal agent. The ingestion increases the secretion of the mucous membranes of the respiratory tract. As an expectorant used the sodium salt of benzoic acid.

Ethyl alcohol

In medical practice, the ethyl alcohol is used primarily as an external antiseptic and irritant tool for rubdowns, compresses, etc., are Widely used in various dilutions for manufacturing nastoykas, extracts and dosage forms for external use.

Sodium tetraborate

Colorless transparent, legkovymyvaemye crystals or a white crystalline powder. Soluble in water, glycerin, insoluble in alcohol. Applied topically as an antiseptic.

Citric acid

A substance having an antioxidant effect (due to the binding of ions of metals of variable valency) and preventing blood clotting. In medicine Oba is and as a preservative widely used in the food industry.

Albumin human serum

Protein, which is very important fraction of human plasma, the body maintains the osmotic pressure in blood circulation and is used to supply the tissues and organs. Preparation of albumin is a clear, viscous liquid amber. Albumin is a classic regulator activity purified interferon.

Glycerine

Thick transparent colourless hygroscopic liquid, miscible with water. Used as a solvent in liquid medicines, to create a certain consistency in soft medicinal forms.

Sodium carboxymethylcellulose

Water-soluble polymer that forms when mixed with water kaleidophone solutions and gels (depending on the concentration of the polymer), derivatives of cellulose (sodium CMC, methylcellulose, hydroxypropylcellulose and others) have found wide application in the pharmaceutical industry as stabilizers and prolongation of action of drugs in eye drops and as bases for ointments and gels.

Preparation of the gel is as follows.

Sodium carboxymethyl by autoclaving. In the resulting basis consistently add all substances included in the composition of the gel, thermostatic, pour warm gel in sterile jars of dark glass and sealed them with sterile lids.

The resulting tool is a whitish-grayish gel, soluble in water (1:20) with the formation of kaleidophone solution (pH 7,00,5). After application on broken skin or mucous membranes gel dries education film, which has an additional protective effect on damaged surface. Re-application can be done on film. Property fundamentals are such that the polymer network does not prevent the absorption of active substances from the upper layers with repeated application. Thus, it is possible to achieve high local concentrations of interferon at a relatively low activity of the gel. If desired, the film can peel off or wash off with water.

For disclosure of the invention the results of the clinical study, the gel:

The gel was investigated in 30 patients aged 18 to 55 years with disease duration (genital and labial herpes) not less than 6 months. Patients of the control group (10 persons) received "Zovirax" on pam was carried out at random as they come.

The gel used by application to affected areas 3-4 times a day. The course of treatment ranged from 2 to 10 days (average 3-5 days).

Clinical efficacy was assessed on the basis of clinical, biochemical parameters and data virological survey in the form of aggregate estimates of effect.

Clinical characteristics of patients

The study included 30 patients with severe exacerbation (2-3 times per month) of recurrent herpes at the age of 18-55 years. Among them were 14 men and 16 women, localization of herpes sores in patients are presented in table. 1.

The majority of patients were in the early recurrence of the disease. Earlier in these patients, conventional treatment was ineffective and did not affect the recurrence rate.

Treatment started at different stages of infection: during precursors (burning, itching, low-grade fever), on the first day of relapse, the second day of relapse (increase in clinical symptoms - increased redness and swelling, increase in the number of vesicles expressed subjective feelings), with the development of General phenomena (General malaise, weakness, chills).

The results of the 2-day use - and General phenomena. By the end of the second day after the start of therapy gel was observed stabilization process, continued formation of new vesicles. The third day was observed the beginning of a regression of the lesions. The reaction temperature, the phenomena of intolerance and allergic reactions to the application of the gel was not observed (see tab. 2 and 3).

The impact of the proposed composition for the maintenance of antigen herpes virus (conductometric method)

Comparison of the levels of antigen (AG) herpes virus before treatment and 12 days after treatment showed a significant reduction in the number of AG: negative reaction in 17 patients, to slabopolojitelen in 13 patients, which clearly correlates with clinical manifestations.

The effect on the immunological parameters of blood

All the patients showed a significant reduction in immunoregulatory index (with a small decrease in the number of T-helper cells and a significant increase in T-suppressor), reduced activity of natural killer cells, activated T-cells, receptors for HLA-DR+.

The invention is illustrated by the following examples,

Example 1. Patient C., 28 years 7 years suffers recurrent labialis herpes is AMI gave no result. The patient was admitted on day 3 from the beginning of the next relapse. He was appointed a gel of the following composition, wt.%:

Genetically engineered interferon Alfa-2, thousand IU/ml - 5 - 500

Vitamin E - 0,01 - 0,1

Methionine - 0,01 - 0,1

Benzoic acid - 0,01 - 0,1

Citric acid - 0,01 - 0,1

Albumin human serum - 0,02 - 0,5

Ethyl - 1 - 10

Glycerol - 2 - 20

Sodium carboxymethylcellulose - 0,5 - 2,5

Sodium tetraborate - 0,1 - 1,0

Water Up to 100.0 h

The drug was applied 4 times a day. On the 2nd day started fading painful to 5 days hearth epithelials. Duration magnetizing period was 3 months. Was posted in the same second course of treatment, then at 6 months (follow-up) relapse did not occur. No side effects the drug did not cause.

Example 2.

Sick W, 29 years. Suffering from recurrent genital herpes for 2 years. Duration magnetizing period varies from 2 to 4 months. Treatment conventional methods to no avail. Entered the period of prodromal symptoms. The patient was assigned to a gel of the following composition, wt. %:

Genetically engineered interferon Alfa-2, thousand IU/ml - 5 - 500

Vitamins to anti scar is n human serum - 0,02 - 0,5

Ethyl - 1 - 10

Glycerol - 2 - 20

Sodium carboxymethylcellulose - 0,5 - 2,5

Sodium tetraborate - 0,1 - 1,0

Water Up to 100.0 h

The drug was applied 3 times a day. The disappearance of subjective sensations occurred already in the first day of using the product. Developed the eruption was minor and complete epithelialization of the lesion was observed for 5 days. Within 6 months (follow-up) relapse did not occur.

Thus, it should be noted that the gel has a number of advantages: high therapeutic activity, does not cause side effects, easy to use.

Compared with the prototype of this drug has a higher efficiency and a wider range of actions, as included in the gel antioxidants enhance antiviral and antimicrobial activity of interferon, stabilize membranes of body cells from the damaging effects of various agents that enhance the reparative function of the skin. The distinctive properties of the drug allow you to use the gel not only for treatment of herpetic skin lesions, but also for the treatment of wounds, burns, abscesses, etc., diseases, when the use of Haiti gel many times on film, formed after primary treatment. Thin film fundamentals, which is formed after absorption of active substances in the tissue, providing additional protection to the damaged surface, while maintaining the gas exchange with the ambient air and without disturbing the cellular respiration of tissues.

The multiplicity of application of a preparation it is possible to vary the dose in a wide range, achieving high local concentrations of interferon with a relatively small activity gel.

High bioavailability of the drug makes it highly economical, since it allows to achieve the desired therapeutic effect when using smaller quantities of interferon than in the case of the prototype.

References

1. Bryukhanova L. K., and others Pediatrics, 1982, 7, S. 55-57.

2. Bugaev N. P. and others In kN.: Viral hepatitis. M., 1987, S. 167-173.

3. Linnik L. F. and others In kN.: Experimental studies in ophthalmology. M., 1986, S. 132-134.

4. Malinovskaya Century. Century. and other Issues of Virology, 1989, 2, S. 180-183.

5. Kalinin T. Y. and Parfenov centuries the Journal of Microbiology, 1985, 10, S. 3-7.

6. Parfenov Century. Century. and other Antibiotics and chemotherapy, 1990, T. 35, 9, S. 38-41.

7. RF patent 2114 is th gel, containing interferon, characterized in that the use of genetically engineered interferon alpha-2, and optionally, vitamin E, methionine, benzoic acid and citric acid, albumin human serum, ethyl alcohol, glycerin, sodium carboxymethylcellulose, sodium tetraborate in the following ratios, wt. %:

Genetically engineered interferon Alfa-2, thousand IU/ml - 5 - 500

Vitamin E-tocopherol - 0,01 - 0,1

Methionine - 0,01 - 0,1

Benzoic acid - 0,01 - 0,1

Citric acid - 0,01 - 0,1

Albumin human serum - 0,02 - 0,5

Ethyl alcohol - 1,0 - 10,0

Glycerin - 2,0 - 20,0

Sodium carboxymethylcellulose - 0,5 - 2,5

Sodium tetraborate - 0,1 - 1,0

Water Up To 100

 

Same patents:

The invention relates to pharmacology and medicine, in particular to the preparation of solid dosage forms of the drug rapamycin, which includes a core and a sugar coating

The invention relates to the composition of polyols for the production of tablets

Antiseptic tablets // 2184534
The invention relates to the field of medicine and relates to antiseptic tablets, which can be used to treat diseases of the throat and mucous membranes of the oral cavity

The invention relates to medicine, in particular for the treatment of diabetes drug fast action - mortar domestic genetically engineered (recombinant) human insulin, prepared in the cartridges and/or bottles
The invention relates to medicine, in particular to the means for local Antirheumatic therapy

The invention relates to pharmaceutical industry and relates to drugs used in obstetric practice for the treatment and prevention of infectious and inflammatory diseases and dysbacteriosis
The invention relates to medicine, namely oncodermatology, medical cosmetology, pharmacology
The invention relates to medicine, Hepatology, gastroenterology and clinical lymphology, to methods of treatment of chronic viral hepatitis

The invention relates to the field of medicine and relates to pharmaceutical compositions containing the c-kit-ligand and hematopoietic factor, a method of increasing levels of stem cells in the peripheral blood, an antagonist of c-kit ligand, antisense molecules of nucleic acid, the method of increasing levels of peripheral blood cells ex vivo

The invention relates to medicine, in particular to the conjugates of interferon formula I

< / BR>
where R and R', independently of one another, represent lower alkyl; X represents NH or O; n and n' are integers, the sum of which ranges from 600 to 1500; and the average molecular weight parts of polyethylene glycol in the conjugate is from 26000 to 66000 Yes, and to a method for conjugate PEG--IFN with antiproliferative activity, as well as to a method of treatment or prevention immunomodulatory diseases
The invention relates to medicine, namely to Oncology, and can be used for the treatment of patients with non-Hodgkin's lymphoma II-IV stages of the disease

The invention relates to the field of medicine and pharmacology and applies to new effectors of interferon against viruses genital herpes and human papilloma
The invention relates to medicine and can be used in the treatment of concomitant chlamydial herpes infection in women with inflammatory diseases of the pelvic organs (PID)

The invention relates to medicine, Hepatology, to methods of treatment of chronic viral hepatitis
The invention relates to medicine, more specifically to oncourology, and may find application in the treatment of malignant tumors of the kidney with metastases
The invention relates to the venereal diseases and urology, and is intended for the integrated treatment of benign tumors of the urethra associated with urogenital infections

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

Up!