RU2068691C1 - Agent for treatment of viral diseases caused by herpes virus - Google Patents

Abstract

FIELD: medicine, virology. SUBSTANCE: proposed agent used as antiherpetic drug is para-aminobenzoic acid. Preparation is effective for treatment of herpetic damage of the different localization. EFFECT: enhanced effectiveness of agent.

Description

 The invention relates to medicine, in particular to the treatment of viral diseases caused by the herpes virus.

 Specific antiviral virusostatic drugs used in the clinic are known. These include deoxyribonuclease. However, experimentally, the antiviral effect of DNAase in clinical use did not bring the desired results.

 In addition, the clinic uses 5-iodine-2-deoxyuridine, which, due to toxicity, is not administered under the conjunctiva, but is used in the form of drops. The use of drops of this drug for more than 10 days can have a toxic effect on the epithelium of the cornea and conjunctiva, causing the phenomenon of follicular allergic conjunctivitis, acupuncture keratitis, even the development of micropanus phenomena. Therefore, even with good tolerance, the use of this drug for more than 10 days is not recommended.

 Oxolinic ointment is also known, which, in addition to toxicity, has an irritating effect (1).

Known para-aminobenzoic acid PABA (vitamin H ¹ ), which is used to increase the yield of a number of crops, as well as in perfumes as additives in creams and lipsticks to protect the skin from the damaging effects of UV rays as a screening non-toxic substance. Before antibiotics were discovered, PABA was a cure for typhus and rickettsiosis.

 Despite the fact that PABA has been known since the beginning of the 20th century and in recent years numerous positive qualities have been established, it has not yet been widely used in medicine (2).

 The objective of the invention is the expansion of the range of products for the treatment of viral diseases caused by the herpes virus, which do not have negative effects, i.e. non-toxic to the human body.

 The problem was solved in that para-aminobenzoic acid (PABA) was used as an agent for treating diseases caused by the herpes virus.

Para-aminobenzoic acid (PABA) has the following structure C ₇ H ₇ NO ₂ M. m. 137.15.

представляет собой соединение, обладающее широким спектром биологических активностей. ПАБК является природным соединением, содержится в большом количестве в дрожжах и проростках пшеницы, в тканях животных в печени и легких. В качестве лечебного препарата используют синтетическую ПАБК. ПАБК является витамином Н¹ и входит в состав молекулы фолиевой кислоты (группа витаминов В), а также в большое количество других изученных биологических соединений и является физиологически активным метаболитом.

is a compound with a wide range of biological activities. PABA is a natural compound, found in large quantities in yeast and wheat seedlings, in animal tissues in the liver and lungs. As a therapeutic drug, synthetic PABA is used. PABA is vitamin H ¹ and is part of the folic acid molecule (Vitamin B group), as well as a large number of other biological compounds studied, and is a physiologically active metabolite.

 Numerous physiologically active derivatives of PABA are used as painkillers (novocaine, anestezin), lipid-lowering and other drugs. With the introduction of novocaine into the internal environment of the body, it breaks down into PABA and diethylaminoethanol, which has only a vasodilating effect. PABA, released in the body from the composition of novocaine, behaves as an active physiological compound. PABA is not a mutagen, moreover, PABA has antimutagenic properties, dramatically increasing the efficiency of DNA repair after the action of supermutagens.

 PABA has the properties of a powerful reparogen, restoring the genetic structure of bacterial cells after exposure to ionizing radiation. The ability of PABA to regulate the activity of vital enzymes is known, restoring their activity after exposure to heat shock, ultraviolet and ionizing radiation. In particular, PABA is able to increase the activity of DNAase and RNAse, which have the properties of inhibiting the development and reproduction of DNA-containing viruses that cause herpetic keratitis, adenovirus lesions, and others. Based on this, it is clear that PABA as a medicine for viral diseases can mobilize the activity of endogenous enzymatic tissue systems in the fight against viral infection.

In vitro experiments have shown that PABA has a pronounced virucidal effect on the herpes simplex virus (WFP-T, L ₂ ). Upon contact of PABA with HSV in the environment of the Needle for 90 minutes at a temperature of 20 ^o C there was a dose-dependent decrease in the infectious titer. At a maximum dose of 20,000 μg / ml, the difference with control was 3.5 lg TC D ₅₀ .

The effectiveness of PABA on the model of experimental white mice encephalitis is shown. Mice were intraperitoneally infected with a culture of HSV-1, L ₂ at a dose of 10 LD ₅₀ / 0.2 ml. 4 hours after infection, PABA was started (intraperitoneally, at a dose of 5 mg / kg). Injections were given daily for four days. The mortality of experimental mice was reduced by 30% compared with the control. PABA also extended the life expectancy of infected mice by 4 days compared to control. PABA, applied in an effective therapeutic dose, on the 8th day after infection reduced the reproduction of HSV-1 in the brain of white mice by 15 times compared with the control.

 The therapeutic antiviral effect of PABA was also confirmed during clinical trials of the drug. Preliminary clinical trials have yielded positive results.

The treatment is carried out as follows: patients with an appropriate diagnosis were injected with a PABA solution in physiological saline at a concentration of 2 • 10 ^-3 5 • 10 ^-3 % in the form of instillation into the conjunctival sac and subconjunctival injection, depending on the severity and course of the disease, instillations were prescribed from 3 to 8 once a day; and injection under the conjunctiva once a day, 0.2 0.4 ml of the same concentration until the disappearance of clinical symptoms, then the treatment in the form of instillation continued for 7-10 days 2-4 times a day.

 In those patients who had a protracted course of the disease and were immediately treated for 2-3 months with known specific antiviral and nonspecific drugs, cryoapplication of the affected cornea was performed at the beginning of PABA treatment. No other specific antiviral drugs were taken during PABA treatment.

 Example 1. A woman of 35 years old with a diagnosis of primary herpetic treelike keratitis of the right eye. Eye condition: severe mixed conjunctival injection, severe corneal syndrome. The cornea is swollen, in the center of the cornea along the lesion there is erosion. The fluorescence test is positive. Vis 0.08 n / a. From the day of receipt in the form of instillation received a 0.002% solution of PABA for 12 days 6-8 times, on the following days until discharge 4-6 times a day, then after discharge received 2-3 times a day for a week. I received no other specific antiviral drugs, either local or general. On the 6th day, the fluorescence test was negative, from the 5th day there was a positive dynamics of all the symptoms of the disease. On the 12th day, corneal edema disappeared. On the 19th day, at discharge, the eyes are calm, in the center of the cornea there is a slight cloud-like clouding. Vis 0.8 n / a.

 Example 2. A woman of 40 years old with a diagnosis of relapse of herpetic keratouveitis. The primary disease was 4 years ago, as a result of which moderate corneal opacity remained. Complaints of photophobia and moderate eye pain, mild lacrimation. In the center, the surface layers of the cornea are slightly swollen. Moderate conjunctival hyperemia. Vis 0.1 n / a. The patient received, as an instillation, a 0.002% PABA solution 3 times a day for a week. On the 5th day, all the symptoms of the disease disappeared: lacrimation, corneal edema. Vis 0.4 n / a. In addition to PABA, the patient did not receive other drugs.

 Example 3. A boy of 7 years old with a diagnosis of primary metaherpetic keratitis of the right eye. Prior to admission, it was unsuccessfully treated for a month with specific (local and general pyrogenal, IDU 1% and others) and nonspecific medicines in stationary conditions. On admission: a degenerative change in the cornea, covering 1/3 of the cornea in the lower temporal sector (between 4-7 hours), reaching the edge of the pupil. Severe mixed conjunctival hyperemia with edema. Severe corneal syndrome (lacrimation, photophobia, severe pain in the eye). Biomicroscopy revealed defects of the corneal epithelium, the cornea is rough, intense clouding of the deep layers of the stroma. Within 3 days of observation before treatment, corneal degeneration progressed rapidly to the center. After cryoplication with simultaneous instillation of PABA (0.002%) 4-6 times a day, on the 3rd day, a positive dynamics of all symptoms was noted, the fluorescence test was negative (complete corneal epithelization). On the 10th day from the start of treatment, at discharge, the eyes are calm, the cornea is almost transparent. Vis 0.9 n / a.

Example 4. A man of 37 years. The diagnosis is the primary protracted form of herpetic Kerotouveitis. Mixed pyrocorneal injection and conjunctival edema, pronounced corneal syndrome, affects 2/3 of the cornea (upper and outer parts), erosion, swelling of the cornea and upper stroma are noted in places. The cornea was penetrated by newly formed vessels. The pattern of the iris as a result of edema is smeared. Changed the structure of the vitreous. There were cyclical pains. Vis 0.01 n / a. After unsuccessful treatment under stationary conditions (half-dan in the form of instillations and subconjunctival injections, pyrogenal parenterally according to the scheme and topically, antiherpetic gamma globulin topically, vitamin B ₂ , etc. (cryoapplication with simultaneous instillation of 0.005% PABA was performed on the patient for 25 days. due to neovascularization of the cornea, 1% emoxipin was prescribed as instillation 3-4 times a day.On the 3rd day, the corneal fluorescence test was negative, positive dynamics of all symptoms was noted from that day. from the beginning of our treatment, the eye was calm, there was no pericorneal injection, the cornea was almost transparent, there was a regression of blood vessels to the level of limbs, there were no cyclical pains. Vis. 0.1 n / k. 10 days after the end of treatment as a result of hypothermia, the patient turned out to have an exacerbation of the disease: pronounced corneal syndrome, corneal edema, severe unbearable pain in the eye, severe cyclic pain Subconjunctival injections of 0.3 ml of a 0.02% PABA solution were made to the patient from the day of treatment and he received drops in the conjunctival a bag of 6-8 times a day PABA solution of the same concentration. At night, the patient took pain medication. From the 3rd day of treatment, the pain in the eye decreased, the patient stopped taking painkillers and there was a positive dynamics of all the symptoms. Thus, the attack of the disease was stopped. Treatment continued for up to 15 days. After 15 days, the eye is calm, the cornea is almost transparent. Vis 0.1 n / a. Subsequent instillation within 10 days 2-3 times a day is recommended.

 A total of 19 patients received treatment, all 19 people had an improvement in their eye condition and the disappearance of disease symptoms within 3 weeks. During the year, the observed patients had no relapse, all patients noted a state of comfort in the eye from the first days of PABA treatment. Not a single case of drug intolerance or other adverse reactions was observed.

Claims (1)

 The use of para-aminobenzoic acid as a treatment for viral diseases caused by the herpes virus.