RU2178288C2 - Method for treating nervous system diseases - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves administering complex medication therapy. Ozone and oxygen mixture is introduced in liquid carrier into the blood. Ozone and oxygen mixture is introduced as gas into biologically active points. EFFECT: enhanced effectiveness of treatment. 3 cl, 1 tbl

Description

 The present invention relates to the field of nervous diseases and can be used in the complex treatment of patients with vascular and vertebral diseases of the nervous system. A well-known universal factor in the pathogenesis of diseases of the nervous system is hypoxia with the development of metabolic acidosis, "oxidative stress" with activation of lipid peroxidation of membranes, and lipid metabolism disturbance. Despite the presence of common signs of diseases of the nervous system, each of them is characterized by its own characteristics. So, with migraine, an important role is played by a violation of the metabolism of biologically active substances, with discirculatory encephalopathy - atherosclerosis, arterial hypertension and their combination, leading to pathological changes in the vascular wall, progressive cerebrovascular insufficiency. With compression - ischemic neuropathy - nerve trunk ischemia due to compression of nerves and blood vessels, with osteochondrosis - degenerative - dystrophic changes in the intervertebral discs.

 Modern medicine has a whole arsenal of means of influencing a particular pathology of the nervous system. As a rule, the complex therapy carried out at the same time includes the use of tablet forms, the administration of drugs intravenously, intramuscularly. The consequences of such a pharmacological load are usually deplorable. Therefore, the efforts of the developers are aimed at preventing adverse effects on the patient's body through the introduction of therapeutic agents of universal effect, capable of correcting certain violations of various components of homeostasis. In this regard, the attention of researchers is drawn to the study of a wide range of biological effects of ozone.

 The pattern of sanogenetic reactions induced by infusions of ozonized physiological solution in patients with suprasegmental autonomic disorders includes an improvement in the energy metabolism of the nervous system, normalization of lipid peroxidation (LPO) processes of neuronal membranes (P. N 2109512, on 04.27.98). The introduction of ozonized saline solution contributes to the direct activation of oxygen-dependent reactions and improve blood supply to brain tissue. The membrane-stabilizing effect caused by the use of ozonized physiological solution helps to stimulate the processes of transmission, processing and storage of information in the central nervous system, in which the membranes of neurons play a leading role. The positive effect of infusions of ozonized saline on the well-being of patients with discirculatory encephalopathy (c. N 95102346 op. 10.12.97 in BI N 34, 1997) is determined by the normalization of indicators of homeostasis. In patients, there is a leveling of manifestations of metabolic acidosis, blood pH and electrolyte balance are restored, the development of coagulopathic reactions is prevented, the oxygen-transport function of red blood cells is significantly improved, and the plasma lipid spectrum is improved. The use of ozonized physiological solution in patients with migraine helps to stabilize vascular tone, reduce adhesion and aggregation of blood cells, normalizes the metabolism of biologically active substances involved in the pathogenesis of migraine paroxysms. The beneficial effect of ozonized physiological saline is also noted in the treatment of compression - ischemic neuropathy (Z. N 96103722 op. 05.20.98 in BI N 14, 1998). As a prototype, the authors considered a known method for the treatment of autonomic dystonia syndrome (P. N 2124356 op. 10.01.99, in BI No. 1). In accordance with this method, in the treatment of the above pathology of the nervous system, intravenous administration of ozonized physiological solution was added to the traditionally used complex therapy. The result of treatment in accordance with the well-known scheme was a decrease in the frequency and severity of vegetative crises, normalization of sleep and general well-being, including on days unfavorable by geometeorological factors. When using ozonized physiological solution, a decrease in the degree of tension of the functional regulatory systems of the body, an increase in the protective and adaptive capabilities of the autonomic nervous system, were noted. However, the known method is less effective in the treatment of diseases such as migraine, osteochondrosis of the spine, since providing a normalizing effect on various areas of homeostasis, it does not affect the local reflex level of exposure.

 The objective of the invention is to increase the effectiveness of a method of treating diseases of the nervous system.

 The problem is solved by a method of treating diseases of the nervous system by the complex effect on the patient’s body with therapeutic agents, including the introduction of an ozone-oxygen mixture into the bloodstream in a liquid carrier, in which, in accordance with the invention and, according to the indications, a gaseous ozone-oxygen mixture is injected subcutaneously and / or containing 500-5000 μg / l of ozone paravertebrally and to biologically active points according to generally accepted schemes and rules. In the treatment of migraine, 0.5-2.0 ml is administered every other day for 5-6 procedures, and in the treatment of neurological manifestations of osteochondrosis, 5-20 ml of an ozone-oxygen mixture is additionally paravertebral every other day for 5-6 procedures.

 Proposed in the present invention, the additional effect of the ozone-oxygen mixture on biologically active points allows you to run mechanisms that not only enhance the overall effect, but also have an independent sanogenetic effect associated with the implementation of reflex analgesic mechanisms. Creating a “depot” of the ozone-oxygen mixture in the acupuncture point, we achieve a double effect in the form of an effect on the biologically active point in the sedation mode and the implementation of the local metabolic effect of ozone. In this case, the functional activity of both peripheral nerve formations and the structures of the central nervous system are stimulated. The positive effect of paravertebral administration of the ozone-oxygen mixture in patients with neurological manifestations of osteochondrosis of the spine is associated with improved microcirculation in a particular vertebral motor segment, blocking inflammatory reactions by suppressing prostaglandin synthesis, decreasing muscular-tonic neurodystrophic manifestations due to the oxidation of pain mediators, and correcting local metabolic anion disturbances, and correcting local metabolic disturbances equilibrium on the membranes of pain receptors, posobstvuyuschim increase their sensitivity threshold. At the same time, a local desensitizing effect occurs. Thanks to these effects, afferent pathological impulse is interrupted, and the functioning conditions of the segmental apparatus of the spinal cord are improved. Thus, the proposed methods for the regional administration of ACS are pathogenetically substantiated and can significantly increase the effectiveness of the general effect of infusions of ozonized physiological solution on the body in patients with diseases of the nervous system.

 The authors know that in order to achieve a clinical effect in the treatment of diseases of the nervous system, the complex of therapeutic measures is supplemented by effects on biologically active points. In our method of treating migraine, the ozone-oxygen mixture is administered simultaneously in 4-5 biologically active points of different localization, every other day in combination with infusions of ozonized physiological solution, and the points are selected taking into account the severity of the pain syndrome, the localization and nature of the pain, its combination with edema, nausea, vomiting, increased blood pressure. The most commonly used points are: E 36, GI 4, GI 18, RP6, C7, V60, V62, E40. The effect increases when local points are included in the acupuncture recipe depending on the location of the pain. For pain in the temporo-dark region: VB2, VB17, TR 22, VB40, V2, V64, E8; in the occipital region: VB20, VG14, VG20, V 11, IG 14; in the frontal region: VB3, VB14, TR5, TR23, E36, E41. In case of combination with vomiting, the following points were used: P7, VC12, MC6, RP6. With severe swelling: R7, RP2, RP6. In the presence of high blood pressure: P7, MC6, R2. In the treatment of neurological manifestations of spinal osteochondrosis, paravertebral injection of an ozone-oxygen mixture was used: in the paravertebral muscles, at the point of greatest pain, 3 cm lateral of the spinous processes to a depth of 2-6 cm.In addition to paravertebral administration of ACS, its introduction to biologically active points (BAP) is also used. The following points were most often used: E36, V36, V23, V24, V25, V26, V36, V40, RP6, RP9, Gi11, VB34, VG4, VG14. The effect of various physical factors on biologically active points is known, in particular electrical stimulation and cauterization. However, it should be noted that during electrical stimulation of points in the case of careless handling of the equipment, failure to follow the instructions during the session, undesirable consequences are possible, especially if the equipment works from the city network and is not adequately isolated. Cauterization of BAT can also lead to complications in the form of burns, scars, suppurations, so the use of ozone is preferred. The ozone content in the ozone-oxygen mixture is set by the device "Medozons-95-2". The experience of using the described method for the treatment of patients with vascular and vertebral pathology shows that in order to achieve a beneficial effect and eliminate negative effects on the patient, the optimal number of procedures is from 10 to 12, carried out daily. The preliminary clinical trials showed that fewer procedures are not accompanied by a clinical effect, and more procedures are not practical. Doses of introduced ozone in each case are set according to individual indications and taking into account the effectiveness of the procedures. Based on the analysis of statistical data, it turned out that introducing ozone into biologically active points in doses of less than 0.5 ml is ineffective, and introducing more than 2.0 ml is impractical.

 Sources of patent information did not reveal information on the treatment of vascular and vertebrogenic diseases of the nervous system by intravenous infusion of an ozonized physiological solution in combination with the introduction of an ozone-oxygen mixture at biologically active points and paravertebral intramuscular injection of an ozone-oxygen mixture. Therefore, the set of essential features, which provides an increase in the effectiveness of the treatment of vascular and vertebrogenic diseases of the nervous system, meets the criteria of patentability "novelty and technical level."

 The proposed method was treated 40 patients with migraine in the interictal period. The average age of patients was 30.5 years. The duration of the disease ranged from 1.5 to 9 years. Migraine with aura occurred in 32% of cases, migraine without aura - in 68%. The frequency of migraine attacks ranged from 1-3 times a year to 1-2 times a week. All patients complained of headache attacks, recurring, localized most often in one half of the head, mainly in the orbital-frontotemporal region. High-intensity pains were accompanied by nausea, sometimes vomiting, and were characterized by hyperesthesia to light and sound stimuli. The duration of the attack ranged from 3-4 hours to 3 days. In some patients, a change in the side of the headache was observed. As an aura, visual disturbances, paresthesia on the face and limbs were most often noted. In neurological status, micro-focal symptoms were revealed in the form of revitalization of tendon reflexes, anisoreflexia, Tremner symptom, horizontal nystagmus, tremor of fingers of extended arms and eyelids, weakening of convergence. In some patients, sensitive disorders were noted in the form of areas of hypesthesia, sometimes hemigipesthesia. The overwhelming majority of patients showed signs of autonomic dysfunction: bright red persistent dermographism, more pronounced on the side of pain, a "vascular necklace", arterial hypertension or lability of blood pressure, tendency to fainting, tachycardia, acrohyperhidrosis, poor cold tolerance, heat, stuffiness, tendency to allergic reactions, deterioration of health when the weather changes. In the mental sphere, anxiety-phobic syndrome, astheno-depressive syndrome, psychopathic disorders, various character accentuations were detected more often than others. The condition of the patients was evaluated at the beginning and at the end of the course of treatment. Subjective sensations and objective examination data were taken into account. Reactive, personal anxiety was assessed using the Spilberger-Khanin scale, the severity of autonomic disorders was assessed using the autonomic disturbance questionnaire (A.M. Vein, 1991) and cardiointervalography, and the intensity of headaches was visual analogue. The state of cerebral blood flow before and after ozone therapy was studied using transcranial ultrasound dopplerography (TUZDG), changes in the bioelectrical activity of the brain - electroencephalography. Changes in the intensity of blood lipid peroxidation processes were also taken into account. The control group consisted of 24 people who were infused with normal saline (4-6 procedures every other day) in combination with classical acupuncture sessions as a “placebo” procedure. The results of the treatment of migraine patients using the intravenous infusion method of ozonized physiological saline in combination with subcutaneous injection of an ozone-oxygen mixture in biologically active points are presented in table 1.

 As can be seen from the tabular data, the proposed method allows to normalize the psycho-emotional state of patients, reduce the intensity of headaches, and reduce the severity of autonomic disorders. The proposed combination of ozone therapy techniques promotes the development of decentralization processes in the heart rhythm control unit with the optimization of the autonomic tone in the cardiovascular system.

 At the same time, the intensity of lipid peroxidation processes taking part in the pathogenesis of migraine paroxysms decreases. As shown by the results of a Doppler study in the case of patients with migraine without aura in the main and control groups, during the treatment there was a tendency to increase the linear velocity of blood flow, which indicated an increased tone of intracranial vessels of large and medium caliber. However, in the main group, the increase in tone occurred more smoothly, a “soft” tonic effect was observed against the background of leveling of interhemispheric asymmetry of blood flow.

 In the control group, an increase in blood flow velocity was more significant, which indicated the possibility of a repeated attack of migraine. In the case of migraine with aura in patients, a tendency to a decrease in blood flow velocity by 6-8% was observed. In the control group, a tendency toward an increase in vascular tone continued. The analysis of the EEG picture showed that in the main group, against the background of treatment, there was an increase in the total power of the EEG, alignment of the specific gravity of the electrical activity of the delta and theta ranges according to the fronto-occipital gradient characteristic of healthy individuals. A moderate increase in α-activity was noted with a slight suppression of β-rhythm. In the control group, the placebo effect was characterized by the absence of significant changes, indicators of the electroencephalogram. On the whole, a decrease in the degree of disintegration in the functioning of the structures of the limbicoreticular complex was recorded in the main group. The advantages of the proposed method for the treatment of migraine found expression in an increase in the number of patients of the main group discharged from the hospital with a good therapeutic effect compared to the value of the same indicator in the control group (83 and 60%, respectively). Observation of patients after discharge from the hospital showed that in 62% of the patients of the main group, the remission achieved during treatment continued for more than 3 months. In the control troupe, within 3 months, 92% of patients experienced a resumption of migraine attacks.

CLINICAL EXAMPLES
Example No. 1. Patient K., 35 years old, was admitted to the clinic of nervous diseases with a diagnosis of migraine without aura with frequent attacks. The patient complained of paroxysmal headaches in the left temple. The patient’s mother has been suffering from migraine attacks for 50 years, a cousin suffers from fainting, and his uncle has epilepsy from his mother’s side. The patient herself suffers from headache since childhood, paroxysmal headache aggravation from 8 years. According to the patient, during attacks, heaviness appears in the left orbital-temporal region, which turns into a high-intensity pulsating headache in the left temporal-parietal region, the face turns pale, becomes pasty, swollen from the side of pain, and the size of the palpebral fissure decreases. After several hours of headache, vomiting occurs for 24 hours, after which the pain disappears, but a feeling of heaviness remains in the head. Between attacks, he often wakes up in the morning with a feeling of heaviness in his head. Deterioration of health over the past year. In recent months, seizures are repeated 1-3 times a week. Blood pressure 115/75 mm RT. Art. Pulse 68 per minute. In neurological status: the skin is clean, pale, pastiness of the left half of the face, Ch. M. N. without pathology. Tendon reflexes are lively, acrohyperhidrosis, diffuse persistent red dermographism. The patient underwent a course of ozone therapy, consisting of five intravenous drip infusions of an ozonized physiological solution in an amount of 200 ml, pre-sparged with an ozone-oxygen mixture of a certain concentration, every other day, in combination with subcutaneous injection of an ozone-oxygen mixture in biologically active points: E36, G14, RP6, VB2, VB17, TR22, E8. At the same time, the patient received treatment, including indomethacin, amitriptyline, intravenous administration of nicotinic acid from 1 ml to 10 ml according to the scheme on physiological saline, exercise therapy, massage of the neck collar, aeroionization, coniferous baths. As a result of the treatment, the intensity of headache in points decreased from 7.3 to 3.9, reactive anxiety in points decreased from 50.3 to 42.1, and personal anxiety from 52.4 to 51.2 points. The severity of vegetative disorders in points decreased during treatment from 33.6 to 10.4. The vegetative equilibrium index was 316.7 and 238.4, the vegetative rhythm indicator was 8.5 and 6.9 (respectively, at the beginning and at the end of treatment). Y max decreased from 3.1 to 2.4 imp / s, S increased from 21.4 to 23.8 imp / s. According to electroencephalography, an increase in bioelectric activity, the total power of the EEG was noted, the specific gravity of the electrical activity of the delta and theta ranges was aligned according to the frontooccipital gradient. According to dopplerography, there was a moderate increase in the tone of large and medium caliber vessels, a tendency to a smooth increase in the linear velocity of blood flow against the background of equalization of interhemispheric asymmetry of blood flow. As a result of the therapy, a decrease in the intensity of headaches was noted after the second session; after the fourth session, the attacks did not recur. After discharge from the hospital for 3.5 months, migraine attacks did not recur.

 Example No. 2. Patient S., 2.3 years old, was admitted to the clinic of nervous diseases with a diagnosis of migraine without aura. The patient complains of pulsating headaches in the left frontotemporal region. The sister and mother of the patient suffered from migraine. Headaches have become especially disturbing since 17 years. Headache attacks occur once a month on the first or second day of menstruation. Attacks begin with the onset of irritability in the patient, severity appears in the left orbit, swelling of the left half of the face. Headaches last from 6 hours to a day, pulsating pains, accompanied by repeated vomiting, nausea, the patient at the time of the attack notes hypersensitivity to light, sound irritants. Analgesics during an attack practically do not help. In neurological status: there are no focal neurological symptoms. The patient is emotionally labile, anxious. Tendon reflexes d = s, animated. There is tremor of fingers of outstretched hands, a positive symptom of Tremner. A bright red dermographism, tachycardia is revealed. The patient notes a violation of the depth and frequency of breathing, "dissatisfaction with the breath", a feeling of lack of air. The patient underwent a course of ozone therapy, consisting of four intravenous drip infusions of an ozonized physiological solution in an amount of 200 ml, pre-sparged with an ozone-oxygen mixture, a certain concentration, every other day, in combination with subcutaneous injection of an ozone-oxygen mixture in biologically active points: E36, G14, RP6, VB3, VB14. At the same time, treatment was carried out, consisting of methindole, aminalon, pregnin, sibazon, intramuscular administration of xanthinol nicotinate, exercise therapy, massage of the cervical collar, pearl baths, darsonvalization of the scalp. As a result of the treatment, the intensity of the headache in points decreased from 6.3 to 4.2, reactive anxiety decreased from 48.5 to 40.9 points, personal anxiety decreased from 53.2 to 51.5 points. The severity of vegetative disturbances in points was 31.3 at the beginning of treatment, at the end of treatment - 25.8, the index of autonomic equilibrium decreased from 329.3 to 254.6, the vegetative rhythm decreased from 8.5 to 6.7, Y max 2.6 to 2.1 imp / s, S - increased from 21.3 to 23.8 imp / s. On the electroencephalograms, a moderate increase in alpha activity with a slight suppression of the beta rhythm was noted in dynamics. According to a Doppler study, a slight increase in the linear velocity of blood flow was detected against the background of a decrease in the severity of hemispheric asymmetry of blood flow. After discharge from the hospital, the patient was under the supervision of a neurologist, there was the occurrence of attacks of unilateral headache, much lower intensity, without concomitant nausea and vomiting about 1 time per month. Headache lasted no more than 6-8 hours, after which the attack stopped on its own, without requiring medication.

 Treatment of neurological manifestations of osteochondrosis of the spine. The proposed method was treated 52 patients with lumbar localization of osteochondrosis. The frequency of exacerbation ranged from 1 to 5 per year. All patients complained of lower back pain with irradiation in one or both legs, difficulty in movement in the lumbar spine, or gait disturbance to one degree or another. In neurological status, muscle-tonic and neurodystrophic manifestations, limitation of range of motion in the lumbar spine, Laseg symptom, signs of damage to one or two roots (usually L5 or S1) were determined.

 The patients' condition was assessed at the beginning and at the end of treatment in the course of a comprehensive clinical and functional examination: a visual-analogue pain scale, a quality of life questionnaire, the volume of active movements in the lumbar spine, the angle of Laseg’s symptom, the severity of radicular symptoms and neurodystrophic syndrome - in points, were performed vegetative tests with systolic and diastolic blood pressure, needle EMG.

 The control group consisted of 30 people who were treated by the method taken as a prototype using intravenous drip of ozonized physiological saline. In addition, patients of the experimental and control groups received NSAIDs, nicotinic acid, exercise therapy. The treatment results are presented in table 2.

 As can be seen from the tabular data, in patients of the main group there is a significant positive dynamics in the severity of pain, Lasseg symptom and range of motion in the lumbar spine. The dynamics of radicular and neurodystrophic syndromes is slightly less pronounced. The dynamics of needle EMG (a decrease in the duration of PDE) as a result of treatment is also more pronounced in the experimental group.

Clinical examples:
1. Patient V., 49 years old, was admitted to the clinic of nervous diseases with a diagnosis of discogenic radiculoischemia L5 and S1 - roots on the left with severe pain, moderate foot paresis. Complained of intense pain in the lower back and left leg, impaired gait. Pain first appeared 1.5 years before admission to the clinic, their occurrence is associated with hypothermia, physical overload. This aggravation was the fourth. In neurological status, there was a loss of function of L5 and S1 - the roots on the left: pain (YOUR) - 86.32 mm, Laseg symptom - with an angle of 41.2, limitation of range of motion in the lower back: forward - 12.67 mm, back - 10.2 mm, radicular syndrome - II point, neurodystrophic syndrome - III point. According to needle EMG: PDE duration is -14.3 mS from the anterior tibial muscle. A course of ozone therapy was carried out, consisting of paravertebral injections of an ozone-oxygen mixture No. 4 combined (every other day) in combination with the introduction of an ozone-oxygen mixture at acupuncture points: E36, V60, V40, V23, V25, RP6, GI 11, VB34, VG14, VG4.

 As a result of treatment (9 procedures), the following dynamics was achieved: pain (YOUR) - 28.71 mm, Laseg symptom with an angle of 68.3, range of motion in the lower back: forward - 16.32 mm, back - 13.43 mm, radicular syndrome - I point, neurodystrophic - II point. The duration of the PDV of the anterior tibial muscle according to needle EMG was 13.2 mS.

 2. Patient N., 23 years old, was admitted to the clinic of nervous diseases with complaints of moderate pain in the lower back and left leg and difficulty in moving the lower back. Diagnosis: discogenic radiculopathy of S1 root on the left with a mild pain syndrome. Sick 3 years, exacerbations - 1 time per year. In neurological status: pain - 48.3 mm, Laseg symptom - with an angle of 63.7, range of motion in the lower back: forward - 14.5 mm, back - 12.72 mm, radicular syndrome - I point, neurodystrophic syndrome - 0 points. A course of treatment was carried out, including paravertebral administration of the ozone-oxygen mixture No. 4 in combination (every other day) in combination with the introduction of the ozone-oxygen mixture at biologically active points: GI14, VG4, VG14, V60, RP6, RP9, E36, VB34. The following dynamics was achieved as a result of treatment: pain (VAS) - 9.1 mm, Laseg symptom - with an angle of 80, radicular syndrome - 0 points, neurodystrophic syndrome - 0 points, range of motion in the lumbar spine: forward 20.52 mm, back - 15.1 mm. According to needle EMG: before treatment, the duration of the PDE of the anterior tibial muscle is 11.8 ms, after treatment - 10.0 ms.

 As can be seen from the obtained results, the proposed method of treatment is effective, these methods are easy to use, lead to a lasting therapeutic effect in a short time, are economically viable due to the low cost of the procedures.

Sources of information
1. P. 2109512, publ. 04/27/98 , in BI N 12, 1998

 2. 3. N 95102346, publ. 12/10/97, in BI N 34, 1997

 3. 3. N 96103722, publ. 05/20/98, in BI N 14, 1998

 4. P. 2124356, publ. 01/10/99, in BI N 1, 1999 (prototype).

 5. Wayne A. M., Kolosova O. A., Yakovlev I. A., Karimov T. K. “Headache”. M. Medicine 1994

 6. Wayne A. M., Kolosova O. A. "Migraine", 1995

 7. Wayne A. M., Avrutsky V. M. "Pain and anesthesia" M. Medicine 1997

 8. Veselovsky V. P. "Practical vertebro-neurology and manual therapy." Riga, 1991

 9. Zhulev V. M., Lobzin B. S., Badzgaradze Yu. D. "Manual and reflex therapy in vertebral neurology" St. Petersburg, 1991

 10. D. R. Lawrence, P. N. Benitt "Clinical Pharmacology" M. Medicine, 1991

 11. Kukes V. G. "Clinical Pharmacology" M. Medicine, 1991

 12. Hoang Bao Tiau, La Quang Niep "Acupuncture" M. Medicine 1989

Claims (3)

 1. A method of treating diseases of the nervous system by a complex effect on the patient’s body with therapeutic agents, including the introduction of an ozone-oxygen mixture in a liquid carrier into the blood, characterized in that, in accordance with the indications, a gaseous ozone-oxygen mixture containing 500-5000 μg / l of ozone, in biologically active points (BAP) according to generally accepted rules and schemes.  2. The method according to p. 1, characterized in that in the treatment of migraine injected in 0.5-2 ml of ozone-oxygen mixture in BAT every other day for 5-6 procedures.  3. The method according to p. 1, characterized in that in the treatment of neurological manifestations of osteochondrosis of the spine, 0.5-2 ml of the ozone-oxygen mixture is introduced into the BAT every other day for 5-6 procedures, alternating with additional paravertebral administration of 5-10 ml of the ozone-oxygen mixture .

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