RU2191602C1 - Medicinal agent and method of treatment of allergic and pseudoallergic responses - Google Patents

Abstract

FIELD: medicine, pharmacy. SUBSTANCE: invention proposes antibody-base medicinal agent comprising activated form of polyclonal or natural antibodies raised to histamine taken in small or supersmall doses and prepared by multiple successive dilution and external effect being mainly by homeopathic technology. Invention relates also to method of treatment of allergic and pseudoallergic responses using activated form of antibodies raised to histamine taken in small or supersmall doses in mixture of different, mainly in hundredth homeopathic dilutions. Invention provides development of effective preparation used for treatment of allergic and pseudoallergic responses without adverse effects and can be used for treatment and prophylaxis of allergic and pseudoallergic responses. EFFECT: enhanced effectiveness and valuable medicinal properties of agent, improved method of treatment. 1 tbl, 9 ex

Description

 The invention relates to medicine and can be used for the treatment and prevention of allergic and pseudo-allergic reactions.

 The use of antibodies for the treatment of pathological syndromes is known from the prior art (SU 1131508 A, A 61 K 39/00, 1984; SU 1730144 A1, C 12 N 7/00, 1992).

 Medicines (serums, immunoglobulins) based on antibodies used in therapeutic doses are also known (for example, see the Russian Drugs Register, Encyclopedia of Medicines, 7th ed., 2000, pp. 358-359).

 However, the use of these drugs can be associated with undesirable side effects in connection with the introduction of significant doses of foreign protein into the body.

There is a method of treating allergic and pseudo-allergic reactions by exposure to histamine release and histamine-dependent activation of histamine H ₁ receptors (see, for example. Russian Drug Register 2001, 8th edition, M., "Radar", 2000, p. 451, 830) . However, their use is associated with the occurrence of a sedative effect that impedes certain activities.

 The invention is aimed at creating an effective drug for the treatment of allergic and pseudo-allergic reactions based on antibodies, which does not cause side effects.

 The solution to this problem is provided by the fact that the drug contains an activated form of ultra-low doses of monoclonal, polyclonal or natural antibodies to histamine, prepared by repeated serial dilution and external exposure, mainly by homeopathic technology.

The activation (potentiation) of antibodies to histamine in small or ultra-low doses according to this technology preserves biological and pharmacological activity in super-diluted solutions or in saturated dosage forms, which is manifested primarily in the modification of histamine metabolism and in the modification of effects mediated by histamine receptors, including H ₁ receptors. In this case, the direction of action of potentiated antibodies to histamine is determined primarily by the initial physiological state: under conditions close to normal, the effects of potentiated antibodies to histamine are qualitatively identical (unidirectional, synergistic) to the effects of histamine. In allergic and pseudo-allergic reactions, the most important mediator of which is histamine, the effects of antibodies are mainly anti-histamine.

In a method of treating allergic and pseudo-allergic reactions by modifying the effects on histamine metabolism and the effects of histamine mediated by histamine H ₁ receptors, an activated form of antibodies to histamine is used in small or ultra small doses obtained by repeated serial dilution and external exposure.

 In contrast to non-activated forms of antibodies, which are also used in small doses, homeopathic activated (potentiated) antibodies to histamine exert an effect that does not inhibit the activity of endogenous histamine, but modify the activity of histamine metabolism systems and modulate the effects of histamine mediated by histamine receptors.

 The drug is prepared mainly as follows.

To obtain antibodies, the conjugate of histamine with bovine serum albumin is used as an immunogen for immunization of rabbits. Monoclonal monospecific histamine serum is obtained by immunization of rabbits with the indicated immunogen according to one of the traditionally used schemes. Blood sampling is carried out from the marginal ear vein into sterile tubes. After clot retraction, the serum is separated by centrifugation, heated for 56 minutes at 56 ^° C to deactivate complement, poured into 2 ml portions and freeze-dried.

 Serum affinity purification is carried out in a column with macroporous glass, on the granules of which an affinity sorbent conjugate of histamine with polynitrophenyl acrylate is applied.

 The method of obtaining immune antibodies is described, for example, in the book: Immunological methods / ed. G. Fremel, Moscow: Medicine, 1987, p. 9-33.

 Isolated antibodies to histamine are subsequently diluted several times, simultaneously exposing them to standardized according to the rules of homeopathic technology, to obtain small or ultra-small doses (not containing molecules of the starting substance) (see Homeopathic medicines. Guide to the description and manufacture, V. Schwabe, Moscow, 1967, p. 12-38). In this case, a uniform decrease in concentration is made by successive dilution of 1 volume part of the starting substance (antibodies) in 9 volume parts (for decimal dilutions of D) or in 99 volume parts (for hundred dilutions of C) of a neutral solvent with multiple vertical shaking of each dilution obtained and using mainly separate containers for each subsequent dilution to obtain the desired dose (potency).

 External processing in the process of reducing the concentration can also be carried out by ultrasound, electromagnetic or other physical effects.

 A medicine prepared in this way is used, mainly in dosage forms and dilutions accepted in homeopathic practice, in the form of alcohol (aqueous) solutions or tablets (granules) obtained by soaking the filler in the dosage form by saturation with a potentized solution or by direct introduction of the latter into a liquid medicinal product form.

 It is preferable to use a mixture of various, mainly hundred, homeopathic dilutions.

 Example 1

 When studying the effect of antibodies to histamine on the development of immediate hypersensitivity reactions, the severity of anaphylactic reactions in Ba1b / c mice in response to sensitization with heterogeneous protein by normal horse serum (LS) was evaluated.

 Sensitization scheme: Drugs at a dilution of 1/10 were administered sc in 0.3 ml once a day, 5 times with an interval of 4 days. The resolving dose of the drug in a 1/10 dilution was administered iv 0.5 ml on the 7th day after the last sensitizing administration.

 In this case, the following shock pattern was observed: in the first minutes after the introduction of the resolving dose of the drug, excitation was observed, followed by depression. After 10-15 minutes, partial paresis of the extremities occurred, cyanosis, clonic convulsions, shortness of breath appeared. Between convulsions, the animal was in the "frog" position. After 30-40 minutes, death occurred or after 2 hours recovery.

The results were taken into account according to the following criteria:
- - no reaction; + - depressed state, covering eyes; ++ - cyanosis, minor cramps, depression; +++ - cyanosis, clonic convulsions, depression, pronounced paralysis, the position of the "frog"; ++++ - fatal outcome.

 Preparations containing monoclonal antibodies to histamine potentiated by the homeopathic method in a dilution mixture of D3 + D12 + C30 (Anti-G), placebo and drugs were administered as follows.

Group 1
on the 1st, 4th, 8th, 12th and 16th day, sensitization of drugs s / c 0.3 ml
from the 1st to the 10th day the introduction of anti-G (0.2 ml per os)
on the 23rd day (on the 7th day after the last injection of drugs) the introduction of a resolving dose of drugs and recording the results.

Group 2
in the 1st, 4th, 8th, 12th and 16th day, sensitization of drugs was administered subcutaneous 0.3 ml
from 1st to 10th day placebo administration (0.2 ml per os)
on the 23rd day (on the 7th day after the last injection of drugs) the introduction of a resolving dose of drugs and recording the results.

Group 3
on the 1st, 4th, 8th, 12th and 16th day, sensitization of drugs s / c 0.3 ml
from the 14th to the 23rd day the introduction of anti-G (0.2 ml per per os)
on the 23rd day (on the 7th day after the last injection of drugs) the introduction of a resolving dose of drugs and recording the results.

Group 4
on the 1st, 4th, 8th, 12th and 16th day, sensitization of drugs s / c 0.3 ml
from the 14th to the 23rd day, the introduction of a placebo (0.2 ml per os)
on the 23rd laziness (on the 7th day after the last injection of drugs) the introduction of a resolving dose of drugs and recording the results.

 Results. In groups where the course administration of anti-G onset simultaneously with sensitization (1-2), marked differences between control and experience were noted. In the control group (2) only 1 out of 9 mouse survived, while in the experimental group (1) half of the animals survived (4 of 8), and in 3 animals the manifestations of shock were moderate, without the development of pronounced paralysis, which allowed to evaluate its severity in ++.

 In the groups where the anti-G course was administered in the last 10 days before the administration of the resolving dose (3-4), a decrease in mortality was observed in the experimental group relative to the control group (from 85.7% to 66.6%).

 In addition, it should be noted that 3 hours after the 5th (last) immunization of animals in groups 1 and 2, a pronounced anaphylactic reaction was observed in group 2 (control), which manifested itself in an inhibited state, disheveled, cyanosis, which allows us to assess the severity of anaphylactic shock on + / ++. At the same time, no visible reactions were observed in group 1 (see table).

 From the above data it follows that the (potentiated) antibodies to histamine prepared according to the rules of homeopathic technology in ultra-low doses during prophylactic use significantly reduce the severity of allergic reactions of GNT in the form of anaphylactic shock.

 Example 2

 Patient K., 23 years old, turned to an allergist about hay fever with complaints of severe itching of the eyelids, frequent attacks of sneezing, itching and nasal congestion, heavy liquid discharge from the nose, general malaise (lethargy, drowsiness, decreased performance). These symptoms appear annually during the flowering period of cereals. Prescribed: potentiated immune rabbit antibodies to histamine C200: 1 tablet 3 times a day. At a second appearance after a week, the patient noted that after a short exacerbation on the first day of treatment, all allergy symptoms decreased significantly. Objectively: there are no signs of rhinitis and conjunctivitis. Recommended further use of the drug during the season 1 tablet 2-3 times a week in the morning.

 Example 3

 Patient J., 18 years old, turned to an ENT doctor with complaints of periodic nasal congestion and fluid discharge, attacks of sneezing and itching in the nose, itching of the eyelids. Symptoms come in contact with dust and pets. Diagnosis: year-round allergic rhinoconjunctivitis. Recommended: potentiated affinity-purified antibodies to histamine (a mixture of dilution C12 + C30 + C200) - 3 drops of an alcohol solution in a teaspoon of boiled water 1-3 times a day, depending on the severity of the symptoms. With repeated appearance after 1 month, the patient noted a significant decrease in the frequency and severity of allergy attacks.

 Example 4

 Patient K., 52 years old, was hospitalized in the therapeutic department in connection with right-sided lower-lobe pneumonia. After an intramuscular injection of ampicillin, generalized itchy rashes, a headache, and a feeling of swelling in the throat appeared. The patient was prescribed monoclonal antibodies to histamine in a dilution mixture of C200 + C1000, 1 tablet every 15 minutes. After the third dose of the drug, the patient noted a decrease in the sensation of swelling of the pharynx, headache, and itching. 2 hours after the start of treatment, the symptoms of an allergic reaction to the injected ampicillin were completely stopped.

 Example 5

 Patient E., 3 years old, after eating eggs and products containing eggs, itchy erythematous rashes and loose stools appear. Diagnosis: food allergy. Appointed: antibodies to histamine in a mixture of homeopathic dilution D3 + C3 + C30 1 tablet dissolve in the mouth for 30 minutes after consuming these products and 30 minutes after, as well as 2-3 times a day until the rashes disappear. When you visit the doctor again after 1 month, according to the parents, the number of cases of allergic reactions to the mentioned products has significantly decreased, and their severity has decreased. A maintenance dose of the drug is recommended 2 times a week, as well as 30 minutes before eating egg-containing foods. With a repeated appearance after 3 months: according to the parents, allergic reactions were no longer noted.

 Example 6

 Patient P., 7 years old, after consuming 2 bars of chocolate, developed a headache, local swelling of the oral mucosa, and itchy erythematous rashes. Previously, such reactions were stopped with antihistamines. Prescribed: antibodies to histamine in a mixture of homeopathic dilution C12 + C30, 1 tablet dissolve in the mouth every 15 minutes. 45 minutes after the start of treatment, all these symptoms of the pseudo-allergic reaction were stopped.

 Example 7

 Patient S., 34 years old, is observed by a pulmonologist regarding atopic bronchial asthma, worsening in the spring and summer due to the flowering of a number of trees and herbs (confirmed by skin allergy-diagnostic tests). In connection with the approaching period of the exacerbation of the disease, it is recommended to take antibodies to histamine in a mixture of homeopathic dilutions of C12 + C1000, 1 tablet daily until exacerbation and 3 times a day during exacerbation. At a second appearance in a month, the patient noted that asthma attacks were noticeably reduced (compared with the previous season), they are less likely to occur faster stopping. Subjective data are confirmed by peak flowmetry (self-monitoring) and respiratory function. Taking the drug allowed to reduce by 3 times the dose of the taken basic drugs (inhaled glucocorticosteroids).

 Example 8

 Patient T., 25 years old. It is observed by an ENT doctor about chronic vasomotor rhinitis, is forced to constantly use vasoconstrictor drops. At the next exacerbation of the disease, the patient was assigned affinity-purified polyclonal antibodies to histamine in a mixture of homeopathic dilutions C12 + C30 + C200, 1 tablet 3 times a day. Against the background of taking the drug in a patient after 3 hours, nasal breathing steadily recovered, nasal discharge decreased, and headache passed. After stopping the exacerbation, a maintenance dose of 1 tablet daily is recommended. At a repeated appearance after 3 months, the patient noted the absence of rhinitis attacks and related headaches.

 Example 9

 Patient D., 26 years old, turned to an allergist with complaints of frequent attacks of sneezing, itching and nasal congestion, abundant liquid discharge from the nose, general malaise (lethargy, drowsiness, decreased performance). These symptoms appear annually during the flowering period of cereals. Prescribed: potentiated by homeopathic technology, natural antibodies to histamine C200: 1 tablet 3 times a day. Natural antibodies were isolated from a pool of healthy donor sera. In isolation, the method of affinity chromatography (immunosorption) was used on columns with histamine adsorbed onto a solid phase (macroporous aminopropylated glass) (according to the method described, for example, in the book Natural antibodies to low molecular weight compounds. MA Myagkova. M .: MGUL, 2001, p. 70-114).

 At a second appearance after a week, the patient noted that after a short exacerbation on the first day of treatment, all the symptoms of allergies significantly decreased. Objectively: there are no signs of rhinitis and conjunctivitis. Recommended further use of the drug during the season 1 tablet 2-3 times a week in the morning.

Claims (4)

 1. A drug based on antibodies for the treatment of allergic and pseudo-allergic reactions, characterized in that it contains an activated form of monoclonal, polyclonal or natural antibodies to histamine in small or ultra-small doses, prepared by repeated serial dilution and external exposure, mainly by homeopathic technology.  2. The drug according to claim 1, characterized in that a mixture of various, mainly hundred, homeopathic dilutions is used. 3. A method of treating allergic and pseudo-allergic reactions by modifying the effects on histamine metabolism and the effects of histamine mediated by histamine H ₁ receptors, characterized in that they use the activated form of antibodies to histamine in small or ultra-small doses, obtained by repeated serial dilution and external exposure.  4. A method of treating allergic and pseudo-allergic reactions according to claim 3, characterized in that a mixture of various homeopathic dilutions is used.

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