RU2611364C1 - Antiseptic preparation and method for obtaining thereof - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine, namely to industrial preparation of antiseptic preparation for medical purposes. Claimed is antiseptic preparation, which includes nanoparticles of tempered silver in amount from 0.01 to 0.05 wt %, base, represented by viscofluid substance and water in amount not more than 5 wt % of preparation weight. Also claimed is method of obtaining said antiseptic preparation in form of stable hydrosol based on distilled water. Obtained antiseptic preparation, containing dispersed silver nanoparticles, can be used in ophthalmology, ENT, dermatology, dentistry, surgery, urology, obstetrics and genecology, and combustiology.

EFFECT: group of the inventions provides manufacturing and application of products for medical purposes in form of antiseptic hydrosol and gel-ointment preparation for processing respectively mucosal and skin surfaces of human body.

5 cl, 2 dwg, 8 ex

Description

An invention, which is a group of technical solutions united by a common inventive concept, relates to medicine, and more specifically to the industrial preparation of medical antiseptics containing dispersed silver nanoparticles, and can be used in ophthalmology, ENT, dermatology, dentistry, surgery, urology, obstetrics and gynecology, combustiology, etc.

The prior art biocidal concentrate for subsequent dilution containing metal nanoparticles with a size of 5-50 nm, which has a pronounced antimicrobial effect (patent RU 2286951, 2006).

These nanoparticles are obtained as a result of erosion of the material of electrodes placed in circulating water at high-frequency arc discharges.

The generated nanoparticles bind to clusters in the form of associates, attaching the structural elements of water formed under the action of pulsed arc discharges. As a result of the described technology, a concentrate is obtained in the form of a hydrosol: water-suspended clusters of metal nanoparticles (colloidal solution).

In this case, active technological control is carried out over the temperature gradient in the chamber and over the size of the interelectrode gap.

The described technical solution is intended for disinfection of water by a complex effect. So, under the action of high-energy electric discharges in a water stream, in addition to the generated compression waves and ultraviolet radiation, the creation of atomic oxygen and hydroxyl radicals, nanoparticles (60-75 wt.%), Ions (10-15 wt. .%) and microparticles (10-30 wt.%).

Microparticles have metallic properties - they are slightly soluble and practically do not participate in disinfection; Under the influence of gravitational forces, they either precipitate or are discharged together with treated water from the chamber in the form of ballast.

Metal ions have a non-specific inhibitory effect on microorganisms.

Thus, the synergistic effect of physical (compression waves, ultraviolet radiation) and chemical factors (metal nanoparticles, atomic oxygen, hydroxyl radicals) on microorganisms contained in the treated water is practically used.

A feature of the method for producing a dispersed system is the formation of associates due to coordination bonds of nanoparticles with the structural elements of the treated water, which contributes to its sterilization.

Under the action of electric discharges with energy in the range of 1-10 J / cm ³ (discharge frequency 10-100 Hz, current rise rate of 10 ⁶ -10 ⁷ A / s, distance between electrodes 1 cm, water flow rate 1-10 cm ³ / s ) with the material of electrodes made of iron, titanium, copper, silver, metal oxides and some alloys, it was found that in the pH range from weakly acidic to alkaline, clusters of nanoparticles of 5-50 nm in size are formed, which are characterized by an antiseptic and fungicidal effect, i.e. an antimicrobial effect against fungi, viruses and bacteria, respectively but.

Processing the circulating volume of water repeatedly, an aqueous dispersion is obtained with a given concentration of nanoparticle clusters and ions, while the concentration ratio of the ionic form and nanoparticle clusters is performed in accordance with the law of solubility.

Prepared by the proposed method, an aqueous dispersed system (hydrosol) can be used to disinfect other water by adding the resulting biological concentrate (diluting it).

A disadvantage of the known technical solution is the relatively low stability of the resulting dispersion system due to the presence of impurities (agglomeration centers) in the source water, which shortens the shelf life and the intended purpose.

The sedimentation stability of the described colloidal solution is low due to the saturation of the composition with ions during the galvanic dissolution of metal electrodes in the process of concomitant electrolysis.

A more effective antiseptic agent is known in the form of a biocidal concentrate with improved performance characteristics at a high content of functional nanoparticles, described in patent RU 2422377 C2, 2009, which is selected by technical essence and the number of matching features as the closest analogue to the proposed biocidal concentrate.

The known biocidal concentrate intended for subsequent dilution contains clusters of silver nanoparticles 5-50 nm in size, which are obtained by erosion of silver electrodes placed in circulating water as a result of high-frequency arc discharges with active monitoring of the interelectrode gap, when the nanoparticles form associates with water.

A feature of the preparation of the concentrate, which is performed in the form of a stable hydrosol in distilled water with a concentration of up to 100 mg / l, is that the nanoparticles formed, heated in an arc discharge gas medium in the interelectrode gap of 150-250 μm, are quenched when dropped into water.

To exclude the sparkless discharge mode, when high voltage pulses continue to act on the electrodes, saturating the composition with ions, the interelectrode gap is kept in a narrow range by means of an electric drive with a micrometric feed pitch, in accordance with active measurements with a proximity sensor.

With an interelectrode gap of less than 150 μm, technical problems arise of stable ignition of pulsed arc discharges, and more than 250 μm, the nanoparticle quenching mode is not provided.

Clusters of hardened silver nanoparticles are characterized by a higher specific surface energy, as a result of which the sedimentation stability of the prepared biocidal concentrate increases due to the formation of associates: the addition of structural elements of water to a cluster with a developed surface.

The prepared bioconcentrate in the form of a hydrosol with a high content of silver nanoparticle clusters in distilled water, in which there are no agglomeration centers, is suitable for dilution with drinking water (90 wt.%), Which at the same time receives a bactericidal treatment.

When diluting the biocidal concentrate with drinking water, the resulting product contains clusters of silver nanoparticles in an amount guaranteed below the maximum established norm, while maintaining a bactericidal effect.

The maximum achieved concentration of silver nanoparticles of 100 mg / l in the hydrosol is twice as high as in the known analogues.

A disadvantage of the known antiseptic is that its scope is limited by the possibility of disinfecting only water.

Despite the fact that the description of the patent indicates the possibilities of its use in combination with chitosan to affect the human immune system and metabolism in patients with superficial wounds, however, this effect has not been confirmed by any research.

In addition, the disadvantage is that the concentrate is used with the technically possible maximum content of silver nanoparticles not higher than 100 mg / l, since at a higher concentration the solution is stratified. This limits the effectiveness of the intended use of the product and the technological capabilities for creating medical devices more saturated with silver nanoparticles in the form of a gel or ointment preparation.

The technical problem to which the present invention is directed is to increase the functional reliability and effectiveness of the therapeutic and prophylactic effect of the agent prepared in the form of a gel or ointment preparation, thereby providing wider technological possibilities for the intended use.

The inventive antiseptic agent includes hardened silver nanoparticles in an amount of from 0.01 to 0.05 wt%, a base represented by a viscous fluid and water in an amount of not more than 5 wt. % by weight of the product.

In the particular case of the implementation of an antiseptic agent, the concentration of silver nanoparticles in the agent is from 100 to 500 mg / L.

Also in the particular case of the implementation of an antiseptic agent, glycerin and / or lanolin and / or petrolatum acts as a viscous fluid.

As an independent invention, a method for producing an antiseptic is claimed, comprising obtaining a stable hydrosol based on distilled water containing hardened silver nanoparticles of 5-50 nm in size, obtained by erosion of silver electrodes placed in circulating distilled water, as a result of high-frequency arc discharges in a controlled interelectrode gap, which is actively controlled by an electric drive with a micrometric feed pitch associated with a proximity sensor and with a concentration of silver nanoparticles in the range of 0.5-100 mg / l, after which, by stepwise extraction, the base is replaced by a viscous fluid sequentially combined with a hydrosol to a concentration of silver nanoparticles in the resulting product from 100 to 500 mg / l and a water content of not higher than 5 wt. % by weight of the product.

Also in the particular case of the method, glycerin and / or lanolin and / or petrolatum acts as a viscous fluid into which silver nanoparticles are extracted from the prepared hydrosol.

The technical results of the claimed invention is:

- the possibility of using funds for processing, respectively, the mucous and skin surfaces of the human body;

- a higher content of silver nanoparticles in the inventive tool, which improves the efficiency of the tool;

- obtaining a product that does not exfoliate and does not change its physical and technical characteristics and therapeutic properties for a long time.

The combination of a hydrosol with glycerin, lanolin, petroleum jelly, etc. a viscous fluid that is not miscible with water is accompanied by automatic extrusion of silver nanoparticles into an adjacent gel-ointment base, after which pure water is drained and combined with the next portion of the hydrosol to increase the concentration of silver nanoparticles to a predetermined value in the gel-ointment base.

The process of extrusion is controlled by the content in the prepared preparation of water no more than 5 wt. %, above which it significantly reduces the consistency.

The upper limit of the content of silver nanoparticles in the gel-ointment base of the preparation is limited to a concentration of 500 mg / l, since a further increase in the content of silver nanoparticles does not give a noticeable improvement in the medical effect on the treated lesions while slowing down the extraction of silver nanoparticles into the base and the practically unacceptable duration of the technological process as a whole.

The proposed antiseptic agent as a medical device based on, for example, glycerin, containing 100-500 mg / l distributed in the volume of a viscous-flowing base, is convenient for application to the exposed skin surfaces of a person’s body, where it is stored for a long time without flowing, providing an effective therapeutic effect on various types of lesions and diseases, expanding the possibilities of their intended use.

A feature of the preparation of an antiseptic solution with a high content of silver nanoparticles (more than 100 mg / l) is that when the nanoparticles of quenched silver obtained by electric arc directly contact with the gel-ointment base, the latter will be thermally destroyed.

Moreover, it is not technically feasible in serial production to distribute silver nanoparticles directly into a gel-ointment base, bypassing the hydrosol phase.

Therefore, each essential feature is necessary, and their combination in a stable relationship is sufficient to achieve a novelty of quality that is not inherent in the signs of disunity, that is, the technical problem posed in the invention is not solved by the sum of the effects, but by a new super-effect of the sum of the attributes.

The invention is illustrated by drawings, which have a purely illustrative purpose and do not limit the scope of the claims of the totality of the essential features of the formula, which schematically shows a plant for producing a hydrosol.

In FIG. 1 shows a diagram of an apparatus for preparing a hydrosol;

in FIG. 2 is the same electrical block diagram.

A pilot plant (Fig. 1) for preparing a biocidal aqueous concentrate contains two silver electrodes 1 and 2, placed in a vessel 3 and connected by current leads 4 through a parallel-connected storage capacitor 5, having a charging speed of 1-10 μs and whose capacitance is 0.004 μF , with adjustable power supply unit 6.

The vessel 3 is equipped with a pump 7 for circulating the processed fluid.

The discharge current sensor 8 is connected to an oscilloscope 9 for actively monitoring the saturation of distilled water with silver nanoparticles.

The electrodes 1 and 2 through a discharge capacitor 10 (Fig. 2) are connected to the control unit 11 of the voltage pulse generator 12, which are characterized by a short leading edge (several microseconds) in order to ensure a relatively short repetition period.

The pulse generator 12 provides an output voltage in the range of 1-10 kV, an energy pulse of 1-10 J current pulses with an amplitude of 0.5-5 kA and a repetition rate of 1-10 Hz.

The second output of block 11 is connected to an energy storage device (capacitor 5), which is connected through a high-voltage transformer 13 to a block 6 that controls the electric voltage — LATR-ohm, which is powered from the network.

The resonant frequency of the discharge circuit, composed of a storage capacitor 5, current leads 4 and electrodes 1, 2, is set to 30 MHz.

The described installation operates as follows.

When voltage is applied to the electrodes 1 and 2 from the power supply 6, when the breakdown voltage in the interelectrode gap 1-2 (200 μm) is an average of 8 kV, its capacity is discharged through current leads 4, electrodes 1, 2, and discharge gap 1- 2 between the last.

Monitoring the magnitude of the interelectrode gap 1-2 is carried out during the technological process according to the readings of the proximity sensor 8, by means of a regulated micrometric feed of a reversible electric drive (not conventionally shown).

In this case, the discharge pulse repetition rate is 50 Hz, and the duration of one discharge pulse is 3 × 10 ⁸ s.

The hydrosol preparation parameters (colloidal suspensions of silver clusters) are controlled by measurements of the attenuation of the optical beam and opalescence.

The sizes of silver nanoparticles in the prepared hydrosol, measured by an electron microscope, were 5-50 nm.

On the surface of dispersed silver clusters in water, a shell is formed of compounds of silver with dissolved oxygen, which stabilizes the prepared hydrosol.

The sedimentation stability of the prepared hydrosol is controlled by measuring the optical absorption characteristics in the wavelength range of 316–980 nm.

The control was carried out over a period of 36 months and confirmed the immutability of optical absorption, i.e., the absence of separation in a colloidal solution, the absence of sedimentation of silver nanoparticles in distilled water (antiseptic solution).

To prepare the product, the resulting hydrosol is combined, for example, with glycerin and actively mixed, accelerating the process of extraction of silver nanoparticles into glycerin.

After settling the mixture, the water is drained and the extraction operation is repeated until the glycerol is saturated with silver nanoparticles of a given concentration (in the range of 100-500 mg / l), while controlling the water content in the finished product is not more than 5 wt. %

The finished product can be packaged in tubes made of polymer or metal materials.

Tests of prototypes in clinical use for the treatment of patients with various diseases have confirmed the achievement of positive results on the reliability of functioning in a given usage schedule, providing increased effectiveness of the intended action, which allows recommending the invention for practical use in therapeutic and prophylactic purposes for patients.

The invention is illustrated by the following clinical examples of the use of the preparation prepared according to the present invention.

Example 1

Patient L., 19 years old. Received a 2nd degree burn as a result of boiling water on open skin. In order to prevent the occurrence of a local infectious process, a glycerol-based agent containing 450 mg / l silver nanoparticles was applied to a surface measuring 10 × 8 cm. No antibiotic-based drugs were used in this case. Within a week of using the indicated medical product, a positive dynamics of the patient’s recovery and the absence of signs of purulent inflammation of the lesion site were observed.

Example 2

Patient V., 56 years old. A boil appeared on the skin of the back. For 3-4 days, monotherapy was used with a vaseline-based agent containing 500 mg / l of silver nanoparticles, applied to a cotton-gauze swab applied to the bed at night. Four days later, the clinical manifestations of this disease disappeared. A positive result has been achieved.

Example 3

Patient S., 47 years old. The diagnosis is herpetic keratitis. He received treatment with well-known foreign and domestic antiviral ophthalmic drugs. Within 10 days, the dynamics of treatment are weakly positive. All drugs were canceled. The patient began to lay a glycerol-based product containing 110 mg / l of silver nanoparticles per eyelid of the affected eye 2 times a day. After 3-4 days, there was a complete absence of an inflammatory viral focus on the cornea of the right eye. The patient also confidently noted the absence of any complaints and a qualitative improvement in his condition.

Example 4

Patient K., 38 years old. Thermal burn of the thigh 2-3 degrees. The therapy was carried out by irrigating the burn surface with a solution of colloidal silver with a concentration of 75 mg / l 5-6 times a day for 3 days. The dynamics are weakly positive. On the 4th day of therapy, it was decided to change the colloidal silver solution to an ointment based on colloidal silver (with a silver concentration of 450 mg / l). This portion of the ointment was made 2.5 years ago. A pronounced positive dynamics began to be observed from the first day of applying the ointment in the treatment of burns. After 1.5 weeks, treatment was completed.

This clinical example indicates the greater effectiveness of the ointment in connection with a higher concentration of colloidal silver in it than in an aqueous solution. The example also proves the stability of the therapeutic effect of the ointment and its active substance (colloidal silver) for a long time, since the drug made six months ago was used and showed its effectiveness.

The use of the claimed drug in 20 patients confirmed its effectiveness and stability over the duration of the drug.

In addition, we presented studies related to the action of a solution prepared in accordance with the prototype, which also confirmed their effectiveness.

Example 5

Patient K., 41 years old. The diagnosis is “OD-keratitis” (inflammation of the cornea of the right eye). Within a week, she underwent a course of local ophthalmic drip preparations, which are broad-spectrum antibiotics and antiviral substances. Dynamics is negative. Despite the course of therapy, pain, a feeling of a foreign body, inflammation, as well as mucous discharge, increased.

Then, broad-spectrum antibiotics of a systemic nature in the form of intramuscular injections were connected to the treatment of the patient. Positive dynamics were not observed.

Then the patient was canceled for a day by local ophthalmic preparations and used instillation of a solution of colloidal silver in a consistency of 20 mg / l in an amount of 5-6 times a day, 1 drop. A clinically significant effect was noted immediately after the first day of application of this solution. The amount of discharge from the right eye decreased sharply, pain passed, and the injection of the right eye (inflammation) was significantly reduced. There were signs of epithelialization of corneal tissue defects. Three days later, the patient did not notice any disturbing manifestations. Obvious signs of eye recovery were confirmed by regular biomicroscopy - examination of the eyeball with a microscope.

Example 6

Patient I., 30 years old. She got sick with bilateral bacterial conjunctivitis (profuse purulent separation from both eyes). Within 5 days, it was treated locally with a broad-spectrum antibiotic of European production. Treatment without visible positive dynamics.

The antibiotic has been canceled. Instead, the patient began to instill a solution of colloidal silver in a consistency of 40 mg / l, 1 drop three times a day in both eyes. After one day of use, it was completely possible to get rid of purulent discharge. After another two days of instillation, all phenomena of inflammation of both eyes were finally stopped.

Example 7

Patient S., 47 years old. On the right eye was diagnosed with herpetic keratitis. He received treatment with well-known foreign and domestic antiviral ophthalmic drugs. Within 10 days, the dynamics of treatment are weakly positive.

The drugs were canceled. The patient began instillation in the right eye of a solution of colloidal silver in a consistency of 25 mg / l, 1 drop 4-5 times a day. After 3-4 days, there was a complete absence of an inflammatory viral focus on the cornea of the right eye. The patient also confidently noted the absence of any complaints and a qualitative improvement in his condition.

Example 8

Patient S., 55 years old. The diagnosis is a corneal ulcer of the left eye. In the treatment of the left eye, a solution of colloidal silver with a concentration of 30 mg / l was used with a manufacturing period of 6 months ago. Despite the date of manufacture of the solution, it did not change its color (light yellow), and no precipitation was observed at the bottom of the tank. When using this solution in the form of repeated (5-6 times a day) instillation in the left eye, pronounced positive dynamics was observed during 5 days of treatment. After another 3 days, a complete disappearance of a corneal ulcer of the left eye and clinical recovery were detected. In this clinical example, we can state that the quality and stability of this solution of colloidal silver is completely preserved for 6 months and its clinical properties are preserved while fighting infectious agents.

The achievement of the functional, technical, and service characteristics of stable hydrosols prepared on the described setup — colloidal solutions of nanoparticles in distilled water with specified properties and destination parameters, makes it possible to recommend them as effective medical devices.

A comparison of the proposed technical solution with the identified analogues of the prior art did not reveal an identical match of the totality of the essential features of the invention.

The proposed differences of the antiseptic drug for medical use, which directly follow from the statement of the technical problem, are not obvious to therapists of various specializations.

The manufacture of an antiseptic agent in various concentrations can be carried out serially on existing ion-plasma equipment, followed by the use of technology for the extraction of the solid phase of a colloidal solution into an adjacent viscous fluid.

From the foregoing, we can conclude that the invention meets the conditions of patentability.

Claims (5)

1. An antiseptic, including hardened silver nanoparticles in an amount of from 0.01 to 0.05 wt%, a base represented by a viscous fluid, and water in an amount of not more than 5 wt. % by weight of the product. 2. The tool according to p. 1, characterized in that the concentration of silver nanoparticles in the tool is from 100 to 500 mg / L. 3. The tool according to claim 1, characterized in that glycerin and / or lanolin and / or petroleum jelly acts as a viscous fluid. 4. A method of producing an antiseptic agent, including obtaining a stable hydrosol based on distilled water containing hardened silver nanoparticles of 5-50 nm in size, obtained by erosion of silver electrodes placed in circulating distilled water, as a result of high-frequency arc discharges in a controlled interelectrode gap, which is actively regulated by means of an electric drive with a micrometric feed pitch associated with a proximity sensor and with a concentration of silver nanoparticles in the range azone 0.5-100 mg / l, after which, through stepwise extraction, the base is replaced by a viscous fluid, sequentially combined with a hydrosol to a concentration of silver nanoparticles in the resulting product from 100 to 500 mg / l and a water content of not more than 5 wt. % by weight of the product. 5. The method according to p. 4, characterized in that glycerol and / or lanolin and / or petrolatum acts as a viscous flowing substance.

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