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INVENTION
Patent of the Russian Federation RU2132187
METHOD FOR TREATMENT OF SKIN DISEASES AND MUCOSIUM SHELLS AND MAGNETOACTIVE ORGANIC IRON CONNECTION USED IN IT
Name of the inventor: Antipov BG .; Kim VA; Lisitsa VS; Nadysev Yu.F.
The name of the patentee: Antipov Boris G.; Kim Vladimir Anatolievich; Lisitsa Valery Stepanovich; Nadysev Yuri Fedorovich
Address for correspondence: 121471, Moscow, ul.Gvardeyskaya, 14-219, Matveeva RM
Starting date of the patent: 1998.11.12
The invention relates to the field of medicine, namely dermatology, urology and gynecology. For the treatment of diseases of the skin and mucous membranes, an organic iron compound is introduced, which is a ferrocene compound with nitrogen-containing components injected with a suitable carrier, orally in the form of a hydroalcoholic suspension or externally in the form of ointments in an amount of 0.001-1 g based on the active substance, 3 times a day for 30 - 60 days. The proposed method avoids complications and is more effective.
DESCRIPTION OF THE INVENTION
The invention relates to the field of medicine and relates to methods for treating mucosal lesions in the tissues of the oral cavity, skin, muscles, bones, mucous membranes of the urogenital system based on drugs containing magnetoactive organic iron compounds.
The proposed method can be recommended for use in dermatology, cosmetology, dentistry, urology and gynecology with the aim of eliminating tissue defects with subsequent restoration of the circulatory microcirculatory network and regeneration of adjacent tissues, as well as veterinary medicine.
Skin is the outer covering of the human body and animals, performing various functions: protective, respiratory, thermoregulatory, pigment-forming, excretory, etc. Due to violations of these functions, caused by physical, mechanical, chemical influences, metabolic disorders, various pathologies can arise: hyperemia, swelling , Inflammation, dermatitis, scars, ulcers, burns, pyoderma, tumors, etc.
Mucous membranes are an inner shell of organs connected with the external environment and perform a number of similar functions - protective, transport, moisturizing, absorbing, etc. When they are violated, inflammations, erosions, ulcers, tumors occur.
The methods of treating these diseases depend on the cause of the onset, the nature of the damage and its consequences.
Currently, many drugs of both natural and synthetic origin are used to treat skin diseases and diseases of the mucous membrane. Among these drugs are widely used in dermatology such as: boric acid, zinc oxide, xerobes, furacillin and others. However, they require long-term use and do not give good results in treatment. Antibiotics (SU, 1196001), antiseptics (SU, 1805952), corticosteroids (RU, 94017429), proteolytic enzymes (RU, 2027432), and the like are also known. The use of these agents is often accompanied by a number of undesirable side effects. Currently, a significant amount of plant products, for example, based on St. John's wort, cranberry, sea-buckthorn, yarrow, etc., is also used. (GZMinejyan, Collection on Traditional Medicine and Non-traditional Methods of Treatment, Moscow, 1991). However, since diseases of the skin and mucous membranes require, as a rule, a multifactorial effect (analgesic, antiseptic, hemostatic, osmotic, etc.), these agents are not always effective or have an effect only in a number of limited cases.
The method closest to the claimed method is the treatment of trophic ulcers with an ointment containing iron compounds, which is magnetite, as described in published patent application RU 95109228 A1, June 10, 1997.
This technical solution can be specified as a prototype. However, the agent described in this solution contains a hydrophobic filler as a base and does not provide sufficient efficacy.
It is therefore an object of the present invention to provide methods of treatment and an agent with increased efficacy for the treatment of diseases of the skin and mucous membranes.
This object is achieved by the proposed method for treating a magnetoactive ferro-organic compound, which is a ferrocene compound with nitrogen-containing components, selected from the group of compounds with the general structural formula (I) 
wherein R 1 = CN, Cl, Br, J , CH 2 OH,
R 2 = XN- (CH 2) n -CO-, where X = H, COCH 3, n = 1-12,
When administered in an amount of 0.001-1 g 1-3 times a day orally, orally or injectively with a suitable carrier.
These iron compounds exhibiting valuable biomedical properties are novel and constitute the subject of the present invention.
In the analyzed literature, there are no sources describing this set of distinctive features, and the proposed technical solution clearly does not follow for a specialist from the level of modern technology. Thus, it meets the criteria of the invention "novelty" and "inventive step". The proposed invention can be used in clinical medicine and, thus, it meets the criterion of the invention "industrial applicability".
In diseases of the human body tissues accompanied by their defects - ulcerative lesions of mucous membranes and skin, diseases of bone tissue accompanied by tissue fistulas, and others - the main one in treatment is the stimulation and normalization of metabolic processes underlying normal blood circulation and metabolic energy processes based on On the interaction of iron with the receptors of cells and tissues. It is known that for the energy of tissues, which is based on oxidative phosphorylation, the main role is played by iron, which carries out the active transport of electrons.
Important for the processes of stimulation of tissue metabolism are organic compounds of magnetically active fine iron, which differ from ordinary iron by biological activity caused by delocalization of the electron density at large distances of the order of ~ 50 Angstrom, which leads to the appearance of spontaneous magnetization.
The claimed method of treatment based on organic iron compounds (LVS), in addition to activation of tissue phosphorylation processes leading to increased microcirculation of blood, is also characterized by the fact that the fine powder SCD has a selective effect on the so-called ferroceptors which, in addition to specific binding to the magnetoactive particle of the organic compound Iron provides signaling - trigger the receptor process, resulting in the biological effect of joining the cluster ferromagnetic particles to the ferroceptors of tissue cells, initiating a chain of reactions leading to the synthesis of ATP.
OSJ, used in the claimed method of treatment, are secondary messengers, participants in receptor cellular processes. In connection with this, the use of OSJ as a therapeutic drug for affecting the defects of the mucous membranes and tissues of the body is carried out in two directions:
1. Activation of phosphorylation for regulation of microcirculation of blood and lymph.
2. Activation of molecular energy phenomena by means of a receptor process - binding of ferromagnetic clusters by appropriate cell receptors.
OSZH obtained through a chemical reaction in a mixture consisting of ferrocene derivatives formula (IA) FeC 10 H 9 -R 1, where R 1 = CN, Cl, Br, J , CH 2 OH and heterosubstituted lactams in the presence of a catalyst such as nickel Raney, in an amount of from 0.1 to 2% at a temperature of from 100 to 300 o C.
The resulting compound is a powder with a specific gravity of 1.3-1.8 g / cm 3, the electrical conductivity of 10 -5 - 10 -8 ohm / cm 2, and the magnetic susceptibility of 23 G cm 3 / g, continuing up to t = 556 o K .
To illustrate the practice of the invention, the following examples of the preparation of specific compounds can be given.
Example 1
Dimetoksiferrotsena 2.46 g, 1.97 g and 0.04 g dodekalaktama Raney nickel solder glass in a vacuum ampoule and thermostated at the temperature of 200 o C for 24 hours. The resulting product is ground on a ball mill.
Example 2
1.86 g of ferrocene and 12.7 ml of N-acetylpyrolidone with 0.02 g of Raney nickel are heated to reflux in an argon flow for 16 hours. The resulting precipitate was washed with 15 ml of ethanol 3 times and dried under vacuum at 50-60 o C.
For use in medical purposes, grinding of the OSJ is performed by any method up to a finely dispersed state with particle sizes from 0.01 to 50 μm.
The introduction of the agent can be carried out in the following ways:
- orally, in the form of a suspension in a water-alcohol solution;
- intravenously or intramuscularly, directly into the area of tumor localization, in the form of a suspension in a 4% aqueous alcohol solution or a mixture thereof with other solvents, for example dimexide;
- externally, in the form of suspensions in an alcohol solution or in the form of ointments with an oil-alcohol filler.
Dosages of the active compound administered depend on the type of disease, the condition of the patient, his age, weight, etc. And can vary over a wide range from 0.001 to 1 g. In each application, the most effective compositions thereof are used, including solvents such as alcohol, dimexide, water, surfactants such as phospholipids, stabilizers, ointment Bases containing castor or other vegetable oil, essential oils, fatty acids or their ethers, etc.
An advantageous form for dermatological agents are ointments. The most preferred option for the claimed agent is its use as an emulsion ointment. However, depending on the nature of the disease or a defect in the skin or mucous membrane, it is possible to use the agent in the form of a gel, an alcohol-oil solution, a suspension, a paste, vaginal tablets, etc.
With the help of the selection of the dosage form, it is possible to dose the pharmacological agent, regulate the depth of its penetration into the skin and mucous membranes, and also the symptomatic therapeutic effect due to the dosage forms themselves. The agent is applied by application, by irrigation, syringing, using tampons, etc.
Along with external application, it is possible to administer the SSR internally or by injection, especially when treating tumorous skin and mucous diseases.
Oral administration may be recommended alone or as an addition to external administration of the OSJ. Possible intake of OSJ before bedtime 5-15 mg for 30-50 ml of water, in the morning 3-5 mg in 30-50 ml of water. With pains - up to 50 mg at any time.
The following examples serve to illustrate the invention, but do not limit it.
Example 3
Suspension for water-alcohol applications for diseases of the mucous membrane of the oral cavity and urogenital system.
In a 30 ml vial, one gram of the resulting fine-grained OSM is transferred and infused with 30 ml of a 38% alcohol solution for preservation and a steady state of a fine suspension for oral administration.
Example 4
To treat diseases of human body tissues: defects in the skin, muscles and bone structures accompanied by fistulas, an OSG of one gram is used with the addition of 20 ml of castor oil (or other) and 5-20 ml of alcohol.
Example 5
Oil applications are used to treat defects in human tissues, ulcerative processes, including trophic ulcers, tissue fistulas, various erosions and malignant fluid ulcers. From an alcohol-oil solution and a finely dispersed mixture, an ointment is prepared with the use of various excipients from the following calculation: 1 g of fine powder, 30 ml of alcohol-oil solution and 70 g of filler, all this is thoroughly mixed until a homogeneous emulsion is formed and injected into the tube. A thin layer of emulsion is applied to the wound surface and this procedure is repeated several times before tissue regeneration (skin, connective tissue, vessels).
As examples of the implementation of the claimed method of treatment, showing how the method of stimulating metabolic processes in the tissues of the human body is carried out, a number of observations can be cited.
Example 6. History of N.
Patient N., born in 1937. After extraction of the second molar tooth of the upper jaw, periodontitis with a non-healing trophic defect in the mucosa of the alveolar process of the upper jaw developed with a pronounced pain syndrome. Painful phenomena corresponded to signs of irrigation of the second branch of the trigeminal nerve. When examining the region of the distant second molar tooth of the upper jaw left, there was a defect in the mucosa with a swelling of the upper jaw. Palpation of the entire alveolar process of the upper jaw was accompanied by a pronounced pain reaction, which is especially noticeable in the area of the removed tooth, the mucous membrane was bleeding, and palpation of this area was accompanied by pain discharges in the area of the infrarbital nerve.
The patient was placed in a horizontal position on the couch face up and a napkin measuring 2 x 3 cm moistened with a fine suspension of OSJ on the mucosa of the removed tooth for 20 minutes was applied, after which the pain was sharply reduced. This procedure was done several times a day for three days. On the fourth day the patient noted the complete disappearance of the painful reaction in the region of the removed tooth and in the region of the maxilla. The alveolar process of the upper jaw is painless at palpation, the thickening of the mucosa in the area of the diseased tooth has disappeared, on the 4th day after the beginning of treatment the patient was healthy.
Example 7. History of the Disease of F.
The patient F. born in 1935. Suffered for 10 years obliterating atherosclerosis of the vessels of the lower limbs and varicose veins. After injury on the lower third of the shin of both legs trophic ulcers of 3 x 2 cm developed, which were unsuccessfully treated with topical preparations: ointment, levomycol, actovegin ointment, lotions 3% hydrogen peroxide solution, powder xerobes, etc.
Applications of organic compounds of iron (OSJ) in water-alcohol solution have been started. Two weeks later the swelling was significantly reduced and the pain syndrome disappeared. After a month and a half, the trophic ulcers were cleared, covered with a granulation tissue, the defect of the tissue was restored, and healing ensued (see Table 1).
Example 8. History of Disease A.
Patient A., born in 1920. After exacerbation of chronic thrombophlebitis and trauma, a trophic ulcer 2 x 2 cm in size appeared on the lower third of the right shin. Treatment with antibiotics and vascular drugs (teonecol, trental) did not bring significant relief. Wounds decreased, but the tissue defect remained 1 x 1.5 cm.
Started treatment of OSZH in the form of daily applications. On the 7th day after the treatment, active growth of granulation tissue and healing of the skin defect began. After 4 weeks, there was a clinical recovery (see Table 2 at the end of the description).
Example 9. Case history B.
Patient B. 1942 of the river. He suffers for 15 years with varicose veins of the legs. Objectively: a well-muscled physique, soft leg tissues are swollen; Skin integument of shin and foot of bluish shade. Pulse on the peripheral arteries of the feet is reduced. The subcutaneous veins are enlarged and crimped with dense knots. The trophic ulcer 7 x 3 cm is located on the lower third of the left shin with a scanty serous discharge. The bottom and edges of the wound are covered with small islets of pale granulation tissue. The trophic ulcer originated after a domestic trauma 3 months ago. Treatment was carried out by various ointments: levomekol, Vishnevsky ointment and actovigil. Treatment of the effect did not.
Treatment with a drug based on magneto-active organic compounds of iron began on 23.05.98 in the form of daily lubrication of the wound surface with a drug substance. The patient noted improvement in general condition. Pain, swelling decreased, and the wound was covered with a granulation tissue. Along the edges, the growth of epithelial tissue began, after three weeks the wound was closed, the pain and puffiness disappeared (see Table 3 at the end of the description).
Example 10. History of the disease
Patient B.A.D. Born in 1934. For 25 years suffers varicose veins of the legs, complicated by chronic thrombophlebitis. Periodically, trophic ulcers occur on the soft tissues of the shins. Objectively: a normal build, the lower third of the left leg is swollen, cold to the touch, the skin is bluish-brown in color. The trophic ulcer is located in the lower third of the left tibia measuring 6 x 5 cm with a serous discharge. Within 6 months was treated with antibiotics, ointments, lotions without visible effect.
Treatment with the preparation on the basis of magnetically active organic compounds of iron was started on 23.05.98 in the form of daily lubrication of the wound surface with a drug substance. After 7 days, the islands of the granulation began to appear in the wound, and after 4 weeks the entire wound was covered with a new epithelial tissue, and after 10 days the defect of the skin of the tissue disappeared (see Table 4 at the end of the description).
Example 11. Case history A.
Patient A. born in 1976. The diagnosis is erosion of the cervix. This disease suffers for 2 years. In view of the fact that the patient had not yet given birth, an outpatient treatment was applied, which had no effect (tampons with sea buckthorn oil, sanitation of the vagina with a 30% solution of dimexide + tampons with Vishnevsky ointment). Treatment of bacterial vaginosis was carried out by douching, using tampons with drugs intravaginally. The status is gynecological, the vagina is capacious, the neck is eroded, colplescopy revealed elements of ectopia. The body of the uterus and appendages without features. Vaginal discharge is slimy.
The treatment with intravaginal applications of OSJ in alcoholic-oil solution was started. After 3 weeks after the treatment, a positive result occurred - the ulcerous surface of the cervix completely regenerated. Conducted control examinations during the year showed no signs of recurrence of the underlying disease (see Table 5).
Example 12. Case history D.
Patient D. 1948 year of birth She complained of a sharp decrease in body weight, multiple nodes throughout the surface of the body of a dense consistency, a dark color up to 1.5 cm in diameter.
Diagnosis: skin melanoma.
Treatment was started by daily IM and oral administration of OSJ at 3 mg for 1.5 months. In the process of treatment there were pains in the lesions. By the end of treatment, most of the tumor nodes disappeared. Regression of subcutaneous metastases was noted. The condition is satisfactory. The patient is being observed.
Thus, a new highly effective method for the treatment of skin diseases and diseases of the mucous membranes based on organic iron compounds without side effects is proposed, which can be recommended for widespread introduction into clinical practice.
CLAIM
A method of treating diseases of the skin and mucous membranes, characterized in that an organic iron compound is introduced which is a ferrocene compound with nitrogen-containing components of the general formula I 
where R 1 - CN, Cl, Br, J , CH 2 OH;
R 2 - XN- (CH 2) n -CO-, wherein X = H, COCH 3, and n is 1 - 12,
In the amount of 0,001 - 1 g 1 - 3 times a day until complete regeneration of the affected tissues.
2. A process according to claim 1, characterized in that said ferrocene compound in finely dispersed state is applied to the skin or mucosa by application or irrigation in a suitable carrier.
3. The method of claim 2, wherein the addition of said ferrocene compound in the form of an alcohol-aqueous suspension in an amount of 3 to 20 mg per day.
4. A ferrocene compound of general formula I
where R 1 - CN, Cl, Br, J , CH 2 OH;
R 2 - XN- (CH 2) n -CO-, wherein X = H, COCH 3, and n is 1 - 12.
print version
Date of publication 01.04.2007гг
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