RU2132187C1 - Method and magnetic active organic iron compound for treating skin and mucosa disease - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves administering organic iron compound as combination of Ferrocen and nitrogen-containing ingredients with appropriately selected carrier or per os as water-alcohol suspension or externally as ointment at a dose of 0.001-1 g of active substance contents 1-3 times a day during 30-60 days. EFFECT: reduced risk of treatment complications; enhanced effectiveness of treatment. 4 cl

Description

 The invention relates to medicine and relates to methods for treating lesions of the mucous membranes of oral tissues, skin, muscles, bones, mucous membranes of the genitourinary system based on drugs containing magnetically active organic compounds of iron.

 The proposed method can be recommended for use in dermatology, cosmetology, dentistry, urology and gynecology in order to eliminate tissue defects with the subsequent restoration of the circulatory microcirculatory network and the regeneration of adjacent tissues, as well as veterinary medicine.

 Skin is the outer cover of the human and animal body, performing a variety of functions: protective, respiratory, thermoregulatory, pigment-forming, excretory, etc. Due to violations of these functions due to physical, mechanical, chemical influences, metabolic disturbances, various pathologies can occur: hyperemia, edema , inflammation, dermatitis, scars, ulcers, burns, pyoderma, tumors, etc.

 Mucous membranes are the inner shell of organs associated with the external environment, and perform a number of similar functions - protective, transport, moisturizing, absorbing, etc. When they are disturbed, inflammation, erosion, ulcers, and tumors occur.

 Methods of treating these diseases depend on the cause of the occurrence, the nature of the damage and its consequences.

 Currently, numerous 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, xeroform, furatsillin and others. However, they require prolonged use and do not give good results in treatment. Also known are agents based on antibiotics (SU, 1196001), antiseptics (SU, 1805952), corticosteroids (RU, 94017429), proteolytic enzymes (RU, 2027432), etc. The use of these funds is often accompanied by a number of undesirable side effects. Currently, a significant amount of herbal products is also used, for example, based on St. John's wort, cranberries, sea buckthorn, yarrow, etc. (G.Z. Minejyan, Collection of traditional medicine and alternative methods of treatment, M., 1991). However, since diseases of the skin and mucous membranes require, as a rule, multifactorial effects (analgesic, antiseptic, hemostatic, osmotic, etc.), these agents are not always effective or have an effect only in a number of limited cases.

 Closest to the claimed is a method of treating trophic ulcers using an ointment containing iron compounds, which is magnetite, described in published patent application RU 95109228 A1, 10.06.97.

 This technical solution can be indicated as a prototype. However, the tool described in this solution contains a hydrophobic filler as a basis and does not provide sufficient exposure efficiency.

 Thus, the object of the present invention is to provide methods of treatment and agents with increased effectiveness for the treatment of diseases of the skin and mucous membranes.

где R₁ = CN, Cl, Br, J, CH₂OH,
R₂ = XN-(CH₂)_n-CO-, где X = H, COCH₃, n = 1-12,
при введении в количестве 0,001-1 г 1-3 раза в сутки наружно, перорально или инъекционно с подходящим носителем.The problem is solved using the proposed method of treatment with a magnetically active ferroorganic compound, which is a compound of ferrocene with nitrogen-containing components, selected from the group of compounds by the general structural formula (I)

where 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 externally, orally or injection with a suitable carrier.

 These iron compounds exhibiting valuable biomedical properties are new and also form the subject of this invention.

 In the analyzed literature, no sources have been identified that describe this set of distinctive features, and the proposed technical solution does not explicitly follow for a specialist from the level of modern technology. Thus, it meets the criteria of the invention of "novelty" and "inventive step". The present invention can be used in clinical medicine and, thus, it meets the criteria of the invention of "industrial applicability".

 In diseases of human body tissues accompanied by their defects - ulcerative lesions of the mucous membranes and skin, bone diseases accompanied by tissue fistulas, and others - the main treatment is the stimulation and normalization of metabolic processes that underlie normal blood circulation and metabolic energy processes based on the interaction of iron with receptors of cells and tissues. It is known that for tissue energy, which is based on oxidative phosphorylation, the main role is played by iron, which carries out the active transport of electrons.

 Of great importance for the processes of stimulation of tissue metabolism are organic compounds of magnetically finely dispersed iron, which differ from ordinary iron in biological activity due to the delocalization of electron density at large distances of the order of ~ 50 Angstroms, which leads to the appearance of spontaneous magnetization.

 The claimed method of treatment based on organic iron compounds (OSF), in addition to activating the processes of tissue phosphorylation, leading to increased blood microcirculation, is also characterized in that the fine powder of OSJ has a selective effect on the so-called ferroreceptors, which, in addition to specific binding to a magnetically active particle of the organic compound iron provides signal transmission - they start the receptor process, ending with the biological effect of the addition of cluster ferromagnetic h astits to ferroreceptors 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 cell processes. In this regard, the use of OSJ as a therapeutic drug for affecting defects in the mucous membranes and body tissues is carried out in two directions:
1. Activation of phosphorylation to regulate microcirculation of blood and lymph.

 2. Activation of molecular energy phenomena using the receptor process - binding of ferromagnetic clusters to the corresponding cell receptors.

The coolant is obtained by carrying out a chemical reaction in a mixture consisting of ferrocene derivatives of the 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 , electrical conductivity 10 ^-5 - 10 ^-8 Ohm / cm ² and a magnetic susceptibility of 23 G cm ³ / g, persisting up to t = 556 ^o K .

 To illustrate the implementation of the invention, the following examples of the preparation of specific compounds can be given.

 Example 1

2.46 g of dimethoxyferrocene, 1.97 g of dodecalactam and 0.04 g of Raney nickel are sealed in a vacuum glass ampoule and thermostated at a temperature of 200 ^o C for 24 hours. The resulting product is crushed in a ball mill.

 Example 2

1.86 g of ferrocene and 12.7 ml of N-acetylpyrrolidone with the addition of 0.02 g of Raney nickel are boiled in a flask under reflux in an argon stream for 16 hours. The resulting precipitate is washed in 15 ml of ethyl alcohol 3 times and dried in vacuum at a temperature of 50-60 ^o C.

 For therapeutic use, OSJ is ground in any way to a finely divided state with particle sizes from 0.01 to 50 microns.

The introduction of funds 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-alcoholic solution or its mixture 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 administered active compound depend on the type of disease, the condition of the patient, his age, weight, etc. and can vary in a wide range from 0.001 to 1 g. In each case of using the drug, its most effective compositions are used, including solvents, such as alcohol, dimexide, water, surfactants, such as phospholipids, stabilizers, ointments, as the target additives bases containing castor or other vegetable oil, essential oils, fatty acids or their esters, etc.

 The preferred form for dermatological products are ointments. The most preferred option for the claimed funds is its use in the form of an emulsion ointment. However, depending on the nature of the disease or defect in the skin or mucous membrane, it is possible to use the product in the form of a gel, alcohol-oil solution, suspension, paste, vaginal tablets, etc.

 With the help of the selection of the dosage form, it is possible to dose the pharmacological agent, to regulate the depth of its penetration into the skin and mucous membranes, as well as the symptomatic therapeutic effect due to the dosage forms themselves. The product is applied by application, by irrigation, douching, using tampons, etc.

 Along with external use, it is possible to administer OSJ orally or by injection, especially in the treatment of tumorous diseases of the skin and mucous membranes.

 Oral administration may be recommended on its own or as an adjunct to external administration of OSJ. It is possible to take OSJ before bedtime 5-15 mg per 30-50 ml of water, in the morning 3-5 mg in 30-50 ml of water. For pain - 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 oral mucosa and genitourinary system.

 In a 30 ml vial, one gram of the obtained finely divided coolant is transferred and 30 ml of a 38% alcohol solution is poured for preservation and obtaining a stable state of finely divided suspension for oral administration.

 Example 4

 For the treatment of diseases of human body tissues: defects in the skin, muscles and bone structures accompanied by fistulas, OSG is used in the amount of one gram with the addition of 20 ml of castor (or other) oil and 5 to 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 flowing ulcers. An ointment is prepared from an alcohol-oil solution and a finely dispersed mixture using various excipients from the following calculation: 1 g of finely divided powder, 30 ml of an alcohol-oil solution and 70 g of excipient, all this is thoroughly mixed until a homogeneous emulsion is introduced and introduced into the tube. A thin layer of emulsion is applied to the wound surface and this procedure is repeated several times until tissue (skin, connective tissue, vessels) is regenerated.

 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, a number of observations can be made.

 Example 6. History N.

 Patient N., born in 1937. After extraction of the second molar of the upper jaw, periodontitis with a non-healing trophic defect in the mucous membrane of the alveolar process of the upper jaw with severe pain syndrome developed on the left. Pain phenomena corresponded to the signs of irritation of the second branch of the trigeminal nerve. When examining the area of the removed second molar of the upper jaw, a mucous membrane defect with swelling of the upper jaw was noted on the left. 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 extracted tooth, the mucous membrane was bleeding, and palpation of this site was accompanied by pain discharges in the area of the infroorbital nerve.

 The patient was placed in a horizontal position on the couch face up and he was given a 2 x 3 cm napkin moistened with a fine suspension of coolant on the mucous membrane of the extracted tooth for 20 minutes, 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 area of the extracted tooth and in the upper jaw. The alveolar process of the upper jaw is painless upon palpation, the thickening of the mucous membrane in the area of the diseased tooth has disappeared, and on the 4th day after the start of treatment, the patient was healthy.

 Example 7. The history of the disease F.

 Patient F., born in 1935 suffered for 10 years atherosclerosis obliterans of the lower extremities and varicose veins. After an injury, 3 × 2 cm trophic ulcers developed on the lower third of the lower leg of both legs, which were unsuccessfully treated with topical drugs: Levomycol ointment, Actovegin ointment, lotions with 3% hydrogen peroxide solution, xeroform powder, etc.

 Treatment has begun with applications of organic iron compounds (OSF) in an aqueous-alcoholic solution. After two weeks, the edema significantly decreased and the pain syndrome disappeared. After a month and a half, the trophic ulcers were cleansed, covered with granulation tissue, the tissue defect recovered, healing started (see Table 1).

 Example 8. History of Disease A.

 Patient A., born in 1920 after exacerbation of chronic thrombophlebitis and trauma, a trophic ulcer of 2 x 2 cm in size appeared on the lower third of the right lower leg. Treatment with antibiotics and vascular drugs (teonecol, trental) did not bring significant relief. The wounds decreased, but the tissue defect remained 1 x 1.5 cm.

 The treatment of OSJ has been started in the form of daily applications. On the 7th day after treatment, the active growth of granulation tissue and the healing of a skin defect began. After 4 weeks, clinical recovery occurred (see table. 2 at the end of the description).

 Example 9. History B.

 Patient B., born in 1942 Suffers for 15 years with varicose veins of the legs. Objectively: well-built physique, soft tissues of the legs swollen; skin of the lower leg and feet bluish tint. The pulse on the peripheral arteries of the feet is reduced. The saphenous veins are dilated and convoluted with dense nodes. A trophic ulcer of 7 x 3 cm is located on the lower third of the left lower leg with scanty serous discharge. The bottom and edges of the wound are covered with small islands of pale granulation tissue. A trophic ulcer occurred after a household injury 3 months ago. The treatment was carried out with various ointments: levomekol, Vishnevsky ointment and actovigil. The treatment did not work.

 Treatment with a drug based on magnetically active organic compounds of iron began on 05/23/98 in the form of daily lubrication of the wound surface with a medicinal substance. The patient noted an improvement in general condition. Pain, swelling decreased, and the wound began to become covered with granulation tissue. At the edges, the growth of epithelial tissue began, after three weeks the wound closed, pain and swelling disappeared (see table 3 at the end of the description).

 Example 10. The history of the disease B.A.D.

 Patient B. A.D. Born 1934 for 25 years suffers from varicose veins of the legs, complicated by chronic thrombophlebitis. Trophic ulcers on the soft tissues of the lower leg periodically occur. Objectively: of normal physique, the lower third of the left tibia is swollen, chilly to the touch, bluish-brown skin. The trophic ulcer is located in the lower third of the left lower leg with a size of 6 x 5 cm with serous discharge. For 6 months, it was treated with antibiotics, ointments, lotions without a visible effect.

 Treatment with a drug based on magnetically active organic compounds of iron was started on 05.23.98 in the form of daily lubrication of the wound surface with a drug. After 7 days, granulation islands began to appear in the wound, and after 4 weeks the entire wound was covered with new epithelial tissue, and after another 10 days, the skin tissue defect disappeared (see Table 4 at the end of the description).

 Example 11. History A.

 Patient A., born in 1976. The diagnosis is cervical erosion. This disease suffers for 2 years. Due to the fact that the patient has not yet given birth, outpatient treatment was used that did not bring any effect (tampons with sea buckthorn oil, vaginal debridement with 30% Dimexidum solution + tampons with Vishnevsky ointment). The treatment of bacterial vaginosis was carried out by means of douching, the use of tampons with drugs intravaginally. Gynecological status, vagina capacious, cervical erosion, colposcopy revealed elements of ectopia. The body of the uterus and appendages without features. Vaginal discharge mucous.

 Treatment has begun with intravaginal applications of coolant in an alcohol-oil solution. 3 weeks after the treatment, a positive result occurred - the ulcer surface of the cervix fully regenerated. Conducted control examinations during the year did not reveal signs of relapse of the underlying disease (see table. 5).

 Example 12. Case history D.

 Patient D., born in 1948 She complained of a sharp decrease in body weight, multiple nodes over the entire surface of the body of a dense consistency, dark in color up to 1.5 cm in diameter.

 Diagnosis: skin melanoma.

 The treatment was started by daily IM and oral administration of 3 mg of OSG for 1.5 months. During treatment, pain was noted in the lesions. By the end of treatment, most of the tumor nodes disappeared. There was a regression of subcutaneous metastases. The condition is satisfactory. The patient is observed.

 Thus, a new highly effective method for the treatment of skin diseases and diseases of the mucous membranes based on organic compounds of iron without side effects, which can be recommended for widespread use in clinical practice, is proposed.

Claims (4)

1. A method of treating diseases of the skin and mucous membranes, characterized in that the organic iron compound is introduced, which is a ferrocene compound with nitrogen-containing components of the general formula I

where R ₁ is CN, Cl, Br, J, CH ₂ OH;
R ₂ - XN- (CH ₂ ) _n -CO-, in which X = H, COCH ₃ , and n takes the value 1 - 12,
in an amount of 0.001 - 1 g 1 to 3 times a day until the complete regeneration of the affected tissues.  2. The method according to claim 1, characterized in that the said ferrocene compound in a finely divided state is applied to the skin or mucous membrane by application or irrigation in a suitable carrier.  3. The method according to claim 2, characterized in that the indicated ferrocene compound is additionally administered in the form of an alcohol-aqueous suspension in an amount of 3 to 20 mg per day. 4. The ferrocene compound of General formula I

where R ₁ is CN, Cl, Br, J, CH ₂ OH;
R ₂ - XN- (CH ₂ ) _n -CO-, in which X = H, COCH ₃ , and n takes the value 1 - 12.

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