Analgesic and antipruritic tool

 

(57) Abstract:

The invention relates to medicine. It is proposed to apply the alpha-2-interferon as mestnoanesteziruth and antipruritic funds. The product expands the Arsenal of tools specified destination.

The invention relates to medicine, namely to pharmacology.

The aim of the invention is the expansion of the means of restorative action, used as an anesthetic, and antipruritic. Properties to relieve pain and itching are found in representatives of a new class of compounds - of cytokines, including interferon (IFN) used in prophylactic and therapeutic purposes in infectious diseases and for the treatment of tumors /1/. Analgesic and antipruritic action of IFN identified in its application in the composition of soft medicinal forms (ointments, gels, creams, liniments, pastes) in the affected areas of the body (skin, mucous membranes), previously has not been noticed.

Diseases such as chronic recurrent herpetic infection, shingles, diphtheria, neurodermatitis and other (bacterial, viral or other origin) are drawn from 2 weeks to several years, sometimes for life. They soprovoditeljnoj, deteriorating mental and physical condition.

The search for new tools that facilitate the patient's condition is constant /2/.

Active surface local anesthetic is benzocaine, which is widely used in the form of 5 - 10% ointment. It is usually well tolerated. However, this drug has no antimicrobial action /3/.

Local anesthetic action has a 5 - 10% ointment with novocaine /3/. Novocaine is usually well tolerated, but can cause adverse reactions, and for all the ways it should be used with caution. Thus, in some patients, there is increased sensitivity to the drug (dizziness, General weakness, increased blood pressure, collapse, shock). Can develop allergic skin reactions (dermatitis, desquamation, and others). To identify high sensitivity initially appointed novocaine in small doses. Antimicrobial action novocaine is not.

Local anesthetic action has also 5% piromekainovaya ointment /4/. It is used as analgesic in inflammatory diseases of the mucous membranes of the oral cavity. Apply a thin layer on the painful ucast the s weakness, nausea, vomiting, dizziness, drop in blood pressure, kollaptoidnoe state. If necessary, recommended vasoconstrictor tools.

The objective of our invention is to relieve pain or itching of the skin, mucous membranes, accompanying the underlying disease (e.g., infectious diseases of different etiology), human recombinant alpha 2-interferon. Moreover, this effect occurs at a time earlier than is the cure of the underlying disease.

Currently, IFN widely used for the treatment of various infectious and oncological diseases: herpes, shingles, viral hepatitis, acute viral meningoencephalitis, influenza, measles, breast cancer 2 and 3 stages, hairy cell leukemia, chronic mielolakoza, acute leukemia in children, malignant skin diseases (Kaposi's sarcoma, reticulosarcoma, mushroom avium), kidney cancer stage IV, disseminirovannaya melanoma and other /1/.

In Russia and many foreign countries is industrial production of various preparations. In our country NGOs "Vector" and JV "Business consulting investment GOK produced the following preparations: "Agitare" - Hungary, company Egis /7/ "Wellferon" - England, company "Wellcome" /8/, "Feron" - Japan, the company "Toray" /9/ "Roferon-A - Switzerland, company Hoffman-La Roche" /10/ "intron-A" U.S. company "Schering-Plough" /11/, "Berfor" - Austria, company Boehringer lngelheim" /12/.

In Italy produced human recombinant beta-interferon in the ointment "fron" /13/. In our country also developed the preparations in the ointment dosage form /14, 15/.

The IFN used in prophylactic and therapeutic purposes in the form of solutions or soft medicinal forms, which are used by injection or applied on the affected areas of the skin and mucous membranes, nobody noted the presence of analgesic and antipruritic actions. Moreover, IFN-containing ointment, developed at the Institute. Pasteur (St. Petersburg), to relieve pain in the treatment of patients with purulent-inflammatory processes were added benzocaine /14/. The use of IFN in the composition of mild medications to relieve pain and itching offered for the first time. The effect is, on average, 30 minutes after application. In a very complex and serious cases the effect is manifested in a few hours (up to 36 hours). This cessation of pain or itching when using sohranaetsa based alloy anhydrous lanolin and vaseline medical, containing IFN as the active agent with the biological activity of not less than 2 104international units (ME) 1.0 g of ointment. Such a composition used for the treatment of patients with chronic recurrent herpetic infection, shingles, diphtheria, domestic injuries and other after treatment confirmed the disappearance of the symptoms of the underlying disease, including pain and itching, but no one stated that, on average, 30 minutes after application of the ointment on the affected areas of skin or mucous membranes of the first and subsequent regular doses of IFN in the ointment was a relief of the patient, i.e., he had no pain, burning, itching on the back of continued illness, accompanied by obvious symptoms and confirmed by the test results. I.e., in the course of treatment was detected new previously unknown property of human recombinant alpha 2-interferon in topical dosage form.

Check marked effect in patients who have been appointed ointment with IFN, confirmed the presence of analgesic and antipruritic actions: pain, burning, itching disappeared after an average of 30 minutes (or 1-1 .5 hours depending on the severity of the disease) after notnecessary, the disease continued and pathological changes of the skin and mucous membranes remained complaints on pain and itching were observed. Analgesic effect of IFN used in the form of ointments, was far ahead of the time its therapeutic effect.

After it was revealed this pattern began to experience IFN in the form of soft medicinal forms as anesthetic and antipruritic agents. Moreover, these drugs had no toxicity and allergenicity. Indeed, local application of IFN in the composition of ointments gave analgesic (relieves itching) effect even when diseases nemikrobnoy etiology (neurodermatitis, polyarthritis).

In the above-mentioned diseases (especially when shingles and diphtheria) pain is very strong (with shingles they are approaching the most powerful and well-known pain that occurs in myocardial infarction), and their removal is an important issue. Pain can be resolved while using well-known surface local anesthetic medium - benzocaine, novocaine, piromekaina - ointment dosage form, but they do not have terapevticheskii-2-IFN has not only expressed the pain, but significant antiviral and antibacterial action.

Effect of IFN on viruses and bacteria due to its properties to create a state of nonspecific resistance of cells to infection by viruses and stimulating effect on the immune cells /1/. The proposed mechanism of analgesic and antipruritic actions if in topical dosage form is not associated with the above properties, and may be due to a direct effect on the nerve endings of the IFN or products of its breakdown in areas of application to the skin or mucous membranes. For the manifestation of analgesic and antipruritic action of the product is important is prolonged action of IFN in the place of application, which is achieved when it is used in the form of soft medicinal forms, which are well kept on the skin and on mucous membranes and thereby facilitate the gradual release and prolonged action of IFN in the place of application tools (for 0.5-2 hours and more).

The combination of two effects - analgesic and antimicrobial - an advantage ointment-based tools IFN compared with surface local anesthetic drugs, and detailed or viral lesions sustained anesthetic, or antipruritic effect, although no specific complications that may occur when using surface local anesthetic drugs.

As the pharmaceutically acceptable carrier native or stabilized IFN used a mixture of medical vaseline, glycerin and lanolin, the number of which varied, for example:

medical vaseline 28 - 31%,

glycerin 7 - 10%,

the rest lanolin;

or

medical vaseline 87 - 90%,

glycerol 3 - 6%,

the rest is lanolin.

The tool retains its activity at a temperature of +4oC for 4 months - 2 years or more. It does not lose its activity on the skin and mucous membranes of mammals during the treatment of pain and, while there is a gradual absorption of its components. When applied to the affected areas dilution of the preparation of cosmetic creams, vegetable oils, etc., the biological activity of IFN in 1.0 g of the composition is reduced ten times, it is accompanied by a loss of therapeutic effect means, but its analgesic and antipruritic effect is preserved.

Properties to relieve pain and itching is noted in the ointment is about and for the treatment of domestic injuries (burns, cuts, bruises or injuries sustained by athletes, as well as when neurodermatitis, toothache, insect bites, etc. for various injuries there is also a wonderful healing effect means: the healing is very fast without scarring process.

Study of analgesic and antipruritic actions means on the basis of human recombinant alpha-2 interferon was conducted in adults and children suffering from diseases of viral and bacterial etiology, accompanied by pain and itching.

In particular, surveyed verification analgesic and antipruritic actions ointment form of interferon in patients with chronic recurrent herpetic infection in the acute stage in patients with herpes zoster in children suffering from diphtheria.

1. The results of the observations for verification of analgesic and antipruritic actions tool in patients with herpes infection in the acute stage

Were chosen from persons with similar severity of disease and localization of herpes sores. Means on the basis of IFN was first used in the prodromal period and in the first two days of the recurrence of herpes with the advent of clinical rubbed with a glass rod. Analgesic and antipruritic effect was assessed by the disappearance of the patients pain, burning sensations and itching. therapeutic effect was evaluated in terms of the disappearance of the rash and intensity of clinical signs of relapse. As controls were used the results of treatment of patients with drug placebo (ointment base), as well as survey data of patients prior to the use of IFN in the ointment.

Watched 200 patients with labialis herpes. When applied on the affected areas of the mucous funds from 30,0% of patients noted mild relapse without the development of clinical manifestations. In 40.0% of patients abortifacient for relapse (48 hours). However, the duration of pain, burning, itching, ranged from 0.5 to 3 hours after application of the ointment. The duration of the rash was much greater than 48 hours. Facilitating the flow of relapse observed in other 30,0% of patients. However, the duration of pain ranged from 2 to 24 hours after the first application of the ointment (if duration of rash 5 days). Analgesic effect means steadfastly persisted throughout the relapse.

The obtained results show the before (dozens of times), what is therapeutic effect of IFN against herpetic lesions (reduction of their sizes, preventing the emergence of new elements of the rash, a significant acceleration of healing of skin lesions and mucous membranes). The most pronounced analgesic action had a product containing IFN biological activity of not less than 2 104ME on 1.0 g of the composition. A further increase of the biological activity of IFN in the medium did not lead to the acceleration of the manifestations of analgesic action. Drug placebo analgesic and therapeutic activity did not possess.

2. The results of the observations for verification of analgesic effect means when shingles

Means on the basis of IFN was applied 3 times a day on the locations of the lesions for 1 - 2 days to 3 weeks. Treatment was started at the earliest possible period of the appearance of the rash.

To compare the effectiveness of this treatment with traditional methods of therapy of patients was treated oksolinovoj ointment with antiviral action.

Observed 10 patients. When applied to affected areas of skin on the basis of IFN in 3 patients noted mild disease is littelest period pain did not exceed 2 - 4 days after the first application of the ointment - the total duration of the disease up to 3 weeks. When treating oksolinovoj ointment disease lasted 4 - 5 weeks or more. Throughout this time it was accompanied by severe pain.

The presented results indicate that the tool based on the IFN has a very pronounced analgesic effect with shingles. This effect is seen much earlier than is evident therapeutic effect of IFN (5 to 10 times). The most pronounced analgesic action had a product containing IFN biological activity of not less than 2 104ME on 1.0 g of the composition. A further increase of the biological activity of IFN in the medium did not lead to the acceleration of the manifestations of analgesic action. Oxolinic ointment analgesic properties not possessed.

3. The results of the observations for verification of analgesic effect means diphtheria in children

Means on the basis of IFN was applied 2 to 3 times a day on the area of the pharyngeal lymphoid ring on the background of the traditional therapy of this disease. Were used for comparison group children suffering from diphtheria, which was treated by conventional methods (aiy children receiving means, averaged 29 hours, the duration of fibrinous deposits on tonsils - 117, while the duration of the disease - 408 hours. I.e., analgesic effects of IFN in the ointment 14 times ahead of the manifestation of its therapeutic action. The additional use of funds contributed to the reduction of the period of stay of patients in hospital for 3, 4 days.

The presented results indicate that the tool based on the IFN has analgesic effect of diphtheria in children. This effect appeared already in 1 - 2 days after the onset of the disease, significantly more than the manifestation of therapeutic effect of IFN. The most pronounced analgesic effect of diphtheria had a product containing IFN biological activity of not less than 2 104ME on 1.0 g of the composition. A further increase of the biological activity of IFN in the medium did not lead to the acceleration of the appearance of the anesthetic effect.

Thus, in this series of observations was shown a pronounced analgesic effect of topical products on the basis of human recombinant alpha 2-interferon, which was accompanied by a further strong antimicrobial action.

Tested also analgesic and antipruritic action of creams "Lanolin" and "Spermaceti" produced by JSC "Neva cosmetics" after mixing them with human recombinant alpha 2-interferon (at the rate of not less than 2 104ME biological activity of IFN 1.0 g of cream). The basis of the creams did not affect the action of IFN.

The use of gel and creams, containing in its composition IFN with the above activity, have led to the anesthetic effect, which appeared much earlier than was manifested their antimicrobial effect.

Example 1. Patient A., 32 years. Has made a complaint to the emergence of numerous painful rash on the red border of the lips, burning sensation. Diagnosis: exacerbation of chronic recurrent herpetic infection (confirmed by the results of clinical and laboratory studies).

Assigned human recombinant IFN in the ointment. First applique ointment conducted under the supervision of a physician. 40 minutes after treatment rash pain and burning has stopped completely, although visually this herpes in Krasnaia funds was also made 6 hours after the previous (just 3 applications a day). The course of treatment was 6 days, during which complaints of pain, burning, itching was absent. Complete disappearance of herpetic lesions occurred 6 days after the start of treatment.

Example 2. Patient B., ' 73. He complained of severe pain in the palm of the hand after the household injuries. It was noted deep skin damage. Assigned to the painkiller on the basis of IFN in the form of application for 7 hours under plaster.

2 hours after application of the ointment to the wound and surrounding a small area of intact skin, the pain disappeared and never reappeared. After 7 hours of removal of plaster significant changes in wound surface were noted. IFN in the ointment is no longer assigned, because the pain was not renewed. Full restoration of the integrity of the skin occurred 5 days after injury.

Example 3. Patient Century, 50 years. He complained of sharp pain in the forearm burns received in a domestic environment. The patient marked skin burns 1st degree on an area of about 5.0 cm2. Assigned human recombinant IFN in the ointment in the form of applications. 20 minutes after the treatment the pain disappeared and is no longer who is on the cover occurred 4 days after burn.

References

1. Ershov, F. I. //In the book: The interferon system in normal and pathological conditions. - M. , 1996. - S. 171 - 195.

2. A PCT application 93/17709 from 16.09.93, N 22. Remedy for itching. Japan.

3. Mashkovsky, M. D. //Medicines. 10th ed. - M., 1987. - S. 325 - 328.

4. Mashkovsky, M. D. //Medicines. 12th ed. - M., 1993. S. 380 - 381.

5. "IFN" - Russia NGO "Vector".

6. "Viferon" - Russia, joint venture Business consulting investment.

7. "Agitare" - Hungary, company Egis.

8. "Wellferon" - England, company "Wellcome".

9. "Feron" - Japan, the company "Toray".

10. "Roferon-A - Switzerland, company Hoffman-La Roche.

11. "Intron A" U.S. company "Schering-Plough".

12."Berfor" - Austria, company "Boechringer Ingelheim".

13. Alekseev, K. C., Chaldiran E. A. //Dosage form of interferon. Antibiotics and chemotherapy. - 1990. - T. 35, N 9. - S. 51 - 54.

14. Barsukov, A. E., Simchenko P. J.//Applied interferonsource ointment in the treatment of purulent-inflammatory processes. In Proc.: Immunoprophylaxis and interferon therapy of viral infections. /Proc. inst. them. Pasteur - L., 1988. - S. 71 - 78.

15. Kuznetsov, B. N.//Acute respiratory diseases in children. - M., 1986. - S. 71 - 78.

The use of alpha the drug forms on the affected areas of the body.

 

Same patents:
The invention relates to medicine, namely to pulmonology, and for the treatment of lung acute pneumonia
The invention relates to medicine and can be used for the treatment of infectious diseases
The invention relates to medicine, in particular to the treatment of infectious diseases

The invention relates to medicine, namely to methods for treating infectious diseases, including diphtheria

The invention relates to the field of medicine and is intended for treatment of hepatitis
The invention relates to medicine, in particular to Pediatrics, and for the treatment of stenosing laryngotracheitis

The invention relates to medicine, the pharmaceutical industry and applies ointment with human leukocyte interferon

The invention relates to medicine, namely to Oncology, and for the treatment of metastatic liver lesions
The invention relates to pharmacology, specifically to the preparation interferonsource compositions, which can find application in ophthalmology
The invention relates to pharmacology, specifically to the preparation interferonsource compositions, is able to maintain its biological activity, which can be used as drugs for intranasal use, for example, for the preparation of drops in the nose

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

FIELD: medicine, obstetrics.

SUBSTANCE: at the first stage of pregravidic training one should introduce leukinferon per 10000 IU intramuscularly every other day 10 times, at the second stage it is necessary to perform 3 seances of discrete plasmapheresis. The present innovation enables to decrease the frequency in developing gestosis and the risk for abortion due to normalized activity of female immune system, that in its turn, enables to stop virusemia and virusuria, prevent fetoplacental failure and intrauterine fetal infectioning.

EFFECT: higher efficiency of training.

3 ex, 1 tbl

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to an agent with broad spectrum of biological effect. Agent based on natural interferon and/or recombinant interferon of α- and/or β- and/or γ-types. Agent is made in the form of different medicinal formulations and elicits immunomodulating, antibacterial, antioxidant and regenerating effect and designated for both internal using and external applying on skin and mucosa tissues. Invention provides the development of medicinal agent with broad spectrum of biological action. The prolonged administration of preparation doesn't effect on morphological composition of peripheral blood and has no effect on blood coagulation. The preparation doesn't show topical irritation and pyrogenic effect.

EFFECT: valuable medicinal properties of agent.

22 cl, 8 ex

FIELD: medicine, immunology.

SUBSTANCE: method involves inhalation administration of combination of immunocorrecting agents wherein recombinant interleukin-2 is used or its combination with genetic engineering α2-interferon and with the complex immunoglobulin preparation in the daily doses for 5 days depending on age of patient. Before sanitation with an immunocorrecting agent the method involves assay of carrying type by anti-lysozyme activity of microorganisms (resident or transitory) and repeated examination after sanitation course is carried out. Carriers are subjected for additional sanitation with anti-bacterial preparations in change of carrying type from resident to transitory and with taking into account antibiotic-resistance property of the carrier strain. Method allows carrying out the effective sanitation and immune reablement of germ carriers due to recovery of the adequate natural resistance and complex of nonspecific factor of regional and systemic immunity.

EFFECT: improved and effective method for sanitation.

2 cl, 2 tbl, 5 ex

FIELD: oncological diseases.

SUBSTANCE: invention is designed for use in complex treatment of urinary bladder cancer in case of propagation of tumor to sub-epithelium connective tissue. Method comprises transurethral resection and introduction of immune preparations and furacillin solution. Once transurethral resection completed, three-way Foli catheter is transurethrally introduced to patient, through which mixture of standard furacillin solution with 10·106 ME interferon α-2β is injected from the first postoperative day and over following 3-5 postoperative days bringing summary dose of interferon to 50·106 ME.

EFFECT: prevented traumatism of urinary bladder due to single introduction of catheter and assured continuous action of drugs without development of immune complications.

FIELD: agriculture, veterinary science.

SUBSTANCE: during the 1st d after forming raising groups one should once inject intramuscularly a solution of "Complex A" preparation at the dosage of 0.30-0.32 mg/kg body weight for 45-60-d-aged piglets and simultaneously with fodder one should introduce "Lactobifadol" preparation at the quantity of 0.50-0.52 g/kg body weight during the first 1-5 d. The present innovation enables to activate immune system, increase total protein and hemoglobin in blood that in its turn, prevents bronchopneumonia and remove stress in piglets after forming special raising groups.

EFFECT: higher efficiency of prophylaxis.

1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: method involves administering inmmunotherapy with recombinant interferon-α2b in daily dose of 3x106 MU. It is incubated in thermostat during 1 h at 37°C with 100 ml of autoblood and then it is intravenously introduced to a patient during 1-1.5h daily under blood formula control to reach leukocyte content of>4*109 /l, granulocytes >2*109 /l.

EFFECT: eliminated leukopenia and dose-limiting toxicity risk; accelerated treatment course; reduced risk of infectious complications.

FIELD: genetic engineering, proteins, medicine, pharmacy.

SUBSTANCE: invention relates to a method for preparing a fused protein representing immunoglobulin Fc-fragment and interferon-alpha and can be used in treatment of hepatitis. Method involves construction of a fused protein comprising immunoglobulin Fc-fragment prepared from Ig G1 or Ig G3 in direction from N-end to C-end and the end protein comprising at least one interferon-alpha. Fc-fragment and the end protein are joined directly or by a polypeptide bridge. The fused protein is used for preparing a pharmaceutical composition used in treatment of liver diseases and in a method for targeting interferon-alpha into liver tissues. Invention provides preparing the fused protein eliciting with biological activity of interferon-alpha providing its concentrating in liver and showing enhanced solubility, prolonged half-time life in serum blood and enhanced binding with specific receptors.

EFFECT: improved targeting method, valuable biological properties of fused protein.

10 cl, 5 dwg, 9 ex

FIELD: medicine, oncology.

SUBSTANCE: after removing malignant cerebral tumor one should conduct successive course of: cytokinotherapy consisting of 3 intramuscular injections of leukineferon at 48-h-long interval, adaptive immunotherapy with lymphokine-activated killer cells (LAKC) generated in the presence of recombinant interleukin-2 (IL-2). Moreover, LAKC should be introduced into the channel of removed tumor in combination with IL-2 as 2 procedures at 24-h-long interval. Then comes the course of adaptive immunotherapy with cytotoxic lymphocytes (CTL) generated due to cultivating patient's mononuclear blood cells together with dendritic cells loaded with a tumor antigen, in the presence of recombinant IL-2 to be introduced in combination with it into the channel of removed tumor as 2 procedures at 48-h-long interval. For obtaining dendritic cells in patients before operation it is necessary to isolate monocytes to cultivate with granulocytic-macrophageal colony-stimulating factor and interferon-α at maturating dendritic cells in the presence of monocytic conditioned medium and incubation of dendritic cells in the presence of tumor antigenic material for their loading with a tumor antigen. After immunotherapy with CTL on should conduct the course of vaccinotherapy with dendritic cells loaded with a tumor antigen in combination with subcutaneous injections of IL-2. The method enables to induce high specific anti-tumor immune response along with improved quality of life and prolonged duration of relapse-free period.

EFFECT: higher efficiency of immunotherapy.

2 cl, 2 ex

FIELD: medicine, infectology.

SUBSTANCE: one should introduce rhoncoleukin in standard dosages and standard mode in combination with corbiculin for internal intake per 2 g once daily after meals, being pre-dissolved in 50 ml water, at 8-wk-long course. The present innovation enables to decrease the size of liver, favors regression of disease clinical manifestations in shorter period of time and normalization of detoxicational, protein-synthetic, pigment functions of liver and prolonged remission of the disease mentioned due to corbiculin and rhoncoleukin synergism.

EFFECT: higher efficiency of therapy.

3 dwg, 2 ex, 3 tbl

Up!