Composition for transdermal delivery of medications into organism and thereon-based drug form
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions relates to medicine. Described is a composition for the transdermal introduction of medications (M) into a human and animal organism, including cases of urgent drug treatment and prevention of acute pathological conditions. The composition consists of a solution of one or several M in a mixture of at least two solvents: dialkylamide of lower carboxylic acid and (or) alkylpyrrolidone and monoterpenes and (or) monoterpenoids. The total volume concentration of N,N-dialkylamides of lower carboxylic acids or N-alkylpyrrolidones constitutes from 1% to 99% of the mixture volume.
EFFECT: composition makes it possible to realise urgent drug treatment and prevention of acute pathological conditions of a human and animal organism by a simple in implementation, safe and cheap method.
12 cl, 6 dwg, 4 ex
The group of inventions relates to the field of medicine and veterinary medicine, in particular to the development of new dosage forms, and can be used for the emergency care of a person or animal in acute pathological conditions that require the rapid ingestion of drugs (LV).
For the prevention or treatment of several acute pathological conditions required system (aimed at deleted from the introduction of organs and tissues) effect LV. In medical and veterinary practice, to achieve systemic effects BGN they are introduced into the body through the mouth (orally), by injection, through the upper respiratory tract (inhalation), through the mucous membranes (transmucosal) or through the skin (transdermal). The last three routes of administration are also used to achieve local (implemented in the area of introduction) actions LP.
The speed of development of systemic pharmacological effect LV introduced through the mouth, usually insufficient for emergency care [Mashkovsky M. D. Medicines. Manual for doctors. 15 ed. - M.: Publishing house “New wave”, 2005]. The introduction of the LP by mouth is not possible with convulsions, unconscious patient and acute pathological conditions, manifested by repeated vomiting or ileus pediatricain the th path on the interval between the oral cavity and the duodenum.
Intravenous introduction into the body provides a fast (with a latent period of several minutes) systemic effect LV. However, when the convulsions puncturing veins for intravenous LV hampered by the patient's movements. Intravenous LV also hampered due to decrease in diameter punktirnym veins during pathological conditions accompanied by a reduction in venous blood pressure.
For the prevention or treatment of acute pathological conditions apply intramuscular LV [instruction step treatment amazed with combat therapeutic pathology. Approved by the Head of CWMU the USSR Ministry of defense. - M., 1983]. In this case, the systemic effect of the LP can be provided with a latent period of from several minutes to tens of minutes [Mashkovsky, 2005], which in most cases corresponds to the conditions emergency care in acute pathological States of the organism.
The General lack of intravenous and intramuscular injection of LV is the need of the skills of performing the injection, which complicates the application of these techniques to people without such skills, in particular the wounded and the sick, in order to themselves and others. Injections in the absence of the relevant skills creates the risk of infectious complications, damage to the large blood soudo is or nerve trunks. Another disadvantage of intravenous and intramuscular injection of LV is the epidemiological risk posed by used syringes, syringe-tubes and needles.
The disadvantages of injection methods, deprived of the means of inhalation, transmucosal and TRANS-dermal LV in the body. All three ways are the most traditional medical practice and offer a variety of used dosage forms, including liquid dosage forms (solutions, liniments, emulsions, aerosols) and soft dosage forms (ointments, and patches) [State Pharmacopoeia of the USSR. 11th ed. - M.: Medicine, 1990, S. 136-162; Vinogradov, C. M., Katkov E. B.; Mukhin, E. A. Pharmacology with the recipe. - SPb.: Spec lit, 2000, S. 34-68]. The vast majority of the above transdermal and transmucosal dosage forms intended for the introduction of BGN local rather than systemic effects. A relatively new dosage form is a transdermal therapeutic system (TTS) is a dosage form from which BGN enter the bloodstream at a given speed through the skin [Mashkovsky, 2005, S. 13]; it is intended for introduction of the LP, both local and systemic action.
However, inhalation and transmucosal introduction of the LP in the body have some limitations. In particular it does not apply in cases of Nachod is of the patient in a gas mask or respirator (e.g., if the atmosphere is contaminated poisonous, radioactive substances or bacterial aerosols) or when the patient is unconscious.
The limitations of injection, inhalation and transmucosally how the introduction of the LP in the body, can be overcome by using TTS. Examples of industrially produced are TTC system containing hormone (estradiol, testosterone), analgesics (fentanyl, buprenorphine, lidocaine), vasodilator (nitroglycerin, nitrosorbid), hypotensive (clonidine), antiparkinsonian (selegiline, rivastigmine), antiemetics (granisetron), anti-inflammatory (diclofenac), psychotropic (methylphenidate), cholinergic (scopolamine, oxybutynin) tool [No L. Transdermal and transbuccal drug delivery: enhancement using iontophoresis and chemical enhances Doctor's degree thesis, New Jersey, 2010].
The benefits of TTC are no special requirements to the skills of their use and the possibility of prolonged - from several hours to several days - flow LP in the body. However, available on the market currently TTC have a slight performance compared with the means applied by injection, inhalation or transmucosal. Typically the latent period of the pharmacological effect known TTS is a few hours or even days [Bailey P. L. t al. Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy // Anesthesiology, 1990. - Vol.72, No. 6. - P. 977 - 980; Horwitz, E. et al. A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis // Oral Medicine, 1999. - Vol.87. - P. 700-708.; Muijsers et al. Transdermal fentanyl: an updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control // Drugs, 2001. - Vol.61. - P. 2289-2307.; Durand C. et al. Practical Considerations for Optimal Transdermal Drug Delivery // Am. J. Health Syst. Pharm, 2012. - Vol.69, N2. P. 116-124].
Greater performance (latency period of 5-30 min) declared very rarely and almost exclusively for the TTC calculated not on the system and local action contained in LP. Examples are TTC for local anesthesia [U.S. Patent 8273390; Application U.S. 20120108664; Application U.S. 20060140986; U.S. Patent 5985860; U.S. Patent 5667799; U.S. Patent 8273390].
The data presented demonstrate the possibility of obtaining using TTS not only local but also systemic pharmacological effects, the duration of the latent period which is not important to the user. However, these data indicate that the existing TTC do not provide the performance of the LP, sufficient for the acute treatment and prevention of acute pathological conditions. To achieve this goal, dosage form, speed transdermal supply of LP from which the blood would provide the latent period of the pharmacological effect, comparable with that for utilising the introduction of LV.
The issue of intensifying the submission in the body of the LP through the skin topical, as reflected in the number of patent documents. In particular, it is known to use the external physical impacts, not damaging the skin (heat, sono, electricity and iontophoresis) to accelerate transdermal th transfer BGN. The influence of an electric field applied in one of two TTS fentanyl, manufactured by Alza. One of them (Durogesic®matrix for independent use) meters BGN three days with a latent period of the analgesic effect of 12 h [Duragesic-matrix. Instructions for use]. The second (Ionsys® ionophoretically amplification) is three times shorter duration of action, but the latent period analgesic effect reduced to 10 min [Herndon CM, Iontophoretic drug delivery system: focus on fentanyl // Pharmacotherapy. 2007. - Vol.27, N 5. P. 745-754]. Referred to transdermal therapeutic systems require the use of special equipment and can be used only by medical personnel that do not meet the conditions of the emergency in order to self - or mutual.
Another approach to speeding up the submission in the body of the LP through the skin is drug intensification of local blood flow. Increased permeability of the skin to provide LV combined with the introduction of the LP and pharmacological agent that increase local blood flow. Nab is emer, in the patent application U.S. 20120108664 described method of transdermal administration of ibuprofen in conjunction with nitric oxide donors (II), in which a latent period of local (but not systemic) pharmacological effect of ibuprofen is 10-30 minutes
For enhanced transdermal receipt LV also proposed the use of microtemperature skin. Thus, in accordance with the application of the U.S. 20080008745, Horny layer of skin damage special applicators with microneedles. The use of 50 to 100 microneedles with a diameter of 75 μm to intensify the introduction of water-soluble derivatives of naltrexone reduced the time to reach therapeutic concentrations in plasma from 25 hours to 5 hours, increasing to 150 times the amount of BGN delivered into the body for 40 hours In another invention of the [U.S. Patent 6142939] microneedles named device, making the skin holes with a diameter of up to 1000 μm. However, as can be seen from the above example, even when used in the composition of the SMV microneedles, the time to achieve therapeutic concentrations of LP in plasma (5 h) remains an order of magnitude greater than with intramuscular injection (0.5 h) that does not meet the conditions of the emergency. The disadvantages of the described method applies its epidemiological danger associated with damage to the skin with microneedles.
It is known that micrones the tion phase, containing LV, in some cases accelerates its flow through the skin. When applying the oil dispersions of atropine or dexamethasone with particle size LV 0,05-0,30 µm latent period of action of drugs was three times less than the particle size of 20-50 microns. However, despite this, he was a few hours [U.S. Patent 6113921], which is considerably higher than the latent period in intramuscular LP and does not meet the conditions of emergency care in acute pathological States of the organism.
Another known method of intensification of receipt of LV through the skin is a combination of the LP with "accelerators suction". The accelerators include suction sulfoxidov, alcohols, polyols, alkanes, fatty acids and their esters, amines, amides (including urea and pyrrolidone), terpenes, cyclodextrins and surfactants [Sinha V. R. Permeation Enhancers for Transdermal Drug Delivery. Drug Development and Industrial Pharmacy, 2000. - Vol.26, N 11. - P. 1131-1140]. To speed up the absorption of natural origin include essential oils, terpenes and polysaccharides [Fox L. T. et al. The Transdermal Drug Delivery Enhancement by Compounds of Natural Origin. Molecules, 2011. - Vol.16, N12. - P. 10507-10540]. Terpenes categorized as "accelerators suction" due to their positive effect on the permeability of the skin for different compounds, and also due to the fact that natural terpenes classified by the FDA as safe substances [Fox L. T., 2011].
Others who shM-known accelerator of percutaneous absorption LV are alkylamide lower carboxylic acids, because they have high Salvaterra ability and satisfactory biocompatibility [Sinha V. R, 2000; N,N-dimethylacetamide toxnet data]. However, substances such structures usually do not use individually, and in combination with other solvents or detergents [Shemlale A. J. et al. Useful permeation enhancers for transdermal drug delivery // Internat. J. Pharma Research & Development-Online, 2010. - Vol.2, N 5. P. 1-6].
A well-known technique of simultaneous use of not one but two or more substances-accelerators suction. So, for delivery into the body of chelating agents (methionine, glutathione) to bind heavy metals, it is proposed to use a composition with three solvents (water, lower alcohol and dimethyl sulfoxide) [international application WO2005107723 and application U.S. 20080260653]. When this is declared a high rate of LP from it through the skin (0.1-1.0 mg/cm2for 20 minutes, that is up to 3 mg/(cm2·h)).
For transdermal delivery into the body of narcotic analgesic buprenorphine in U.S. patent 6004969 proposed to use a liquid or semi-liquid composition comprising a solvent from the group of terpenes and the solvent from the group of fatty alcohols or glycols. Identified the relationship of these solvents, providing the maximum speed of transdermal resorption of the LP, however, the latent period of therapeutic effect of this introduction was not the several hours.
Known liquid composition in the dosage form of bandage compress-type transdermal delivery into the body antagonists of muscarinic receptors with the aim of relaxation of smooth muscles of the urinary tract [European application ER]. The composition is designed for hours of use, includes an aqueous solution of ethanol and tea tree oil. In the case of a specific ratio of these solvents, according to in vitro experiments, therapeutic concentration of LP was achieved when the square patch 5-50 cm2that is 40 times less than when using solvents separately.
Inclusion of up to 2% limonene in the composition of the liquid pharmaceutical compositions containing unsubstituted or mono-, di - or tizamidine amines or inorganic bases, 16 times increased the rate of transdermal absorption of nonsteroidal anti-inflammatory LV. At the same time achieve therapeutic concentrations LV acid character in plasma was 0.5 to 1.0 h [U.S. Patent 5164416].
According to the information given in the international application WO 2012066537, the inclusion of limonene (up to 5%) in the composition of the liquid pharmaceutical compositions containing octanol (10%), significantly increases the rate of transdermal resorption LP, containing in the molecular structure of primary, secondary or tertiary amino group. If this is m according to in vitro experiments, the estimated time to achieve therapeutic concentrations of LP in plasma is a few hours.
From patent documents known examples of transdermal or transmucosal use some of the LP, which play an important role as a means of emergency prevention and emergency treatment of acute pathological conditions. Among these LP - steroidal anti-inflammatory drugs, such as dexamethasone; anticholinergic such as atropine; antidotes opioid drugs stimulants, such as naltrexone; neuroleptic such as droperidol [Mashkovsky, 2005, S. 572, 209, 65, 157].
In accordance with the data of some of the inventions that describes TTC matrix type or containing accelerators permeability, the latent period of the pharmacological effect of dexamethasone is 12 h [U.S. Patent 4537776] or 16 h [U.S. Patent 7794738] that does not meet the conditions of emergency care in acute pathological States of the organism.
The only example of a composition for use dexamethasone order to provide emergency care, including the right of self - or mutual aid is the composition intended for transmucosal (but not transdermal) applications LV providing the latent period of the pharmacological effect of 5-10 min [European application ER].
Known pharmaceutical compositions for transmucosal (but not transdermal) administration into the body of atrophy is a, providing an equally rapid pharmacological effect as when it is intramuscular. [Application U.S. 20070048229 and U.S. patent 5288497 and 5288498]. In the Application of the U.S. 20070048229, solvent atropine is a mixture of polar solvent and terpenes. Another example transmucosal injection of atropine given in the application for the invention of the Russian Federation 2010136974.
Known compositions for transmucosal (but not transdermal) the droperidola providing LV performance, close to that in intramuscular droperidola [Paten USA 5288497, 5288498 and RF Application 2008105830].
Naltrexone is mentioned among LV intended for prolonged transdermal injection of a polymeric matrix containing liquid and solid components; the latent period of the pharmacological effect is several hours [U.S. Patent 5446070]. With transdermal use in the composition has managed to introduce into the body naltrexone at a dose of that component is not more than one-third of the recommended daily dose in two days [U.S. Patent 4573995]. The claimed composition for use of naltrexone in a variety of ways, including transdermal, for the treatment of chronic inflammatory processes [RF Application 2010136974]. Transdermal introduction of naltrexone in therapeutic doses was provided only by the use of microneedles and demanded value is more time, namely 0.5-7.0) [Application U.S. 20080008745]. As in the above cases with dexamethasone, atropine and droperidol, only when transmucosal the use of naltrexone in the composition was able to obtain a pharmacological effect in terms comparable to those with the intramuscular injection of this LV [international application WO820376, U.S. Patent 6113921 and RF Application 2010136974].
Also known U.S. patent 5240932, which describes the achievement of long-term (1-7 days) analgesia by skin application to pharmaceutical compositions containing the hydrochloric salt of morphine and other opioid analgesics. The effect was achieved through the use of a liquid composition containing solvents of two types - non-polar (terpenes or fragrant oils containing, in a concentration of 1-20%) and polar (aqueous solutions of lower alcohols or lower glycols). It was tested four BGN, and for each of them was set optimal feed rate BGN qualitative and quantitative composition of solvents. The description shows that the ratio of concentrations of polar and nonpolar solvents has a significant impact on the rate of transdermal resorption LV. However, none of the described in the patent compositions were not suitable for emergency treatment. In particular, for 30 minutes after application of transdermal on is the mark of morphine in 10 cm 2the skin surface was not more than 1/10 of its single therapeutic dose.
As in U.S. patent 5240932, unlike other above analogs described compositions containing as solvents LV at the same time used a mixture of polar and nonpolar solvents, and this provides the effect of exposure introduced LV, this patent is the closest analogue of the claimed composition and adopted as a prototype.
The disadvantage of the prototype is that it cannot be applied in situations of emergency treatment or emergency prevention of acute pathological States of the organism.
The purpose of the claimed group of inventions is to develop a composition which would provide the possibility of emergency care required in cases of acute pathological conditions. This solved the technical problem of raising the rate of transdermal administration of medicinal substances with systemic effects.
The set problem is solved by a composition consisting of a solution of the appropriate type of pathology of one or more medicinal substances in a mixture of at least two solvents, the first solvent is selected from N-alkylamides or represents their mixture, and a second solvent selected from monoterpenes or monoterpenoid is or represents a mixture.
At the same time as the first solvent can be selected N,N-dialkylamide lower carboxylic acid or N-acylpyrrole General formula
R2=R1, R1means methyl or ethyl, a R3: denotes H, methyl, ethyl
R1means methyl or ethyl, a R2+R3means trimethylene; or
The composition of the solvent mixture composition is characterized by the fact that the volume ratio of the first and second solvent can be selected from about 1/99 to about 99/1.
The optimum composition of the mixture of the two solvents depends on the input of the LP and is determined empirically. For example, in the case of use as LV droperidola, the volumetric ratio of the first and second solvent can be selected from about 1/1 to 99/1. In the case of use as LV dexamethasone volumetric ratio of the first and second solvent can be selected from about 4/21 to about 99/1. And in the case of LV atropine and naltrexone volumetric ratio of the first and second solvents can be selected from about 1/99 to about 99/1.
Introduced into the composition of the claimed composition LV can be medicines for emergency care, means acting on the Central or peripheral nervous system, cardiovascular system, will provide the optimum system, money, influence on metabolism, immune system, antimicrobial, antiparasitic and antiviral agents. LV entered transdermal part of the claimed composition is selected in accordance with the current recommendations for treatment, emergency care or prevention.
The claimed composition is a separate dosage form, namely the solution, if it consists of low viscosity solvents, or liniment, if it includes viscous solvents.
The second group of inventions is a new dosage form for transdermal introduction of the LP, characterized in that it contains a composition consisting of a solution of the appropriate type of pathology of one or more of the LP in a mixture of at least two solvents, the first solvent is selected from N,N-dialkylamino lower carboxylic acids or N-alkylpyridine or represents their mixture, and a second solvent selected from monoterpenes or monoterpenoids or represents a mixture.
At the same time as the first solvent can be selected N,N-dialkylamide lower carboxylic acid or N-acylpyrrole General formula
R2=R1, Rimeans methyl or ethyl, a R3: denotes H, methyl ethyl
R1means methyl or ethyl, a R2+R3means trimethylene; or
The composition of the solvent mixture composition is characterized by the fact that the volume ratio of the first and second solvent can be selected from about 1/99 to about 99/1.
Mentioned dosage form may be in the form of ointment, liniment, cream, gel or aerosol.
The implementation of a group of inventions can be performed in different ways. For example, the first solvent mixture may be N,N-dimethylacetamide. However, instead of, or together with it can be used in any combination of N,N-dimethylamide formic, propionic acid, or N,N-diethylamide formic, acetic, or propionic acid, or N-ethylpyrrolidin, or a mixture of any of these organic amides. All of these organic amides of carboxylic acids possess similar physicochemical properties that are essential for the implementation of the proposed method: high polarity, solubility, ability to be mixed in any ratio with maloponyatnymi compounds, neutral pH aqueous solutions, high (>150°C) boiling point.
The second solvent mixture used for the dissolution of the LP, can be monoterpene, or oxygen-containing derivatives of monoterpenic series, or a mixture of terpenes and / or is) terpenoids these groups. For example, (+)-limonene, terpineol, Menton, carvon, pinene, camphor, verbena, verbena, verbenon, cineole, turpentine containing up to 78% of terpenes and terpenoids, or eucalyptus oil containing at least 60% terpenoids 1,8-cineole, 1,8-epoxy-para-Mentana and 1,4-cineole.
The inventive composition containing BGN required for emergency care or prevention can be obtained in a known manner of dissolution of the LP in one solvent, or solvent mixture, and then adding the desired amount of one or more solvents. Also this composition may be prepared by dissolving a certain amount of LP in a certain amount of ready-solvent mixture prepared in advance. This solution of the LP in the mixture of solvents can be stored in accordance with the known requirements of the Pharmacopoeia.
The inventive composition containing the solution of the LP in a mixture of two solvents, can be applied to the skin surface using a known dosing devices (measured capacities, including pipettes and dispensers, spray guns, spray cans and other).
The claimed composition BGN in a mixture of the above solvents may be used in the form of other known medicinal forms obtained on its basis: aerosol, emulsion, ointment (including gel, to the eat or liniment), prepared according to known methods using the standard for this dosage form ingredients [Vinogradov, C. M., Katkov E. B.; Mukhin, E. A. Pharmacology with the recipe. - SPb.: Spec lit, 2000. S. 34-68]. In this case, in the manufacture of known dosage forms "active ingredient" ("active principle") is the claimed composition BGN in a mixture of solvents.
So, for example, dosage form, made in the form of ointments may contain not more than 90% ointment bases, surfactants and stabilizers and at least 10% of the active ingredient, that is the particular solution of the LP in the mixture of the first and second solvents. This solution of the LP is dissolved in the lipophilic component, lipophilic-hydrophilic ointment bases or in part lipophilic base, then known for ointments way to populate the rest of the hydrophilic or lipophilic part of the bases, surfactants and stabilizers [State Pharmacopoeia. - 1990. S. 145-146; Vinogradov A. MT - 2000. C. 60-69].
Another example: pharmaceutical form, is made in the form of an aerosol spray can contain biologically active component of the claimed composition BGN in a mixture of solvents, if necessary component facilitating the dispersion (SAS) and a compressed gas propellant in a suitable container with a metering valve [State Pharmacopeia, 1990. - S. 136-138; Vinogradov, C. M. 2000. S. 57-59].
The claimed composition was manufactured and tested in the form of a solution. It has been experimentally determined that when applying the inventive composition to the skin of the back surface of the brush man in the volume of 0.04 ml of 1 cm2at room temperature, it is completely absorbed in less than 10 s, which allows for its distribution on the surface of the skin known technical devices - sprayers (sprinklers), spray cans, spatulas, rolls, tampons and other.
The impact made songs to your body when it is transdermal administration was tested experimentally. The tests were carried out on outbred rats. Animals were divided into several groups containing at least six individuals, including two in the control group. In one control group of animals was not treated (or, depending on the purpose of the experiment, did not prevention). The second control group of animals was injected intramuscularly therapeutic or prophylactic drug in the same dose as experimental animals. In each experimental group experimental animals transdermal introduced (by drawing in the amount of 0.1 ml per plot ventral surface of the neck area of 5 cm2using a pipette, and stencil) a composition containing a given dose of a particular LP in the mixture of the first the second solvent. In each experiment with a specific type of care or prevention used one LP for multiple groups. The experimental group of animals receiving transdermal same LP, differed qualitative composition of the selected solvents. For the composition of the same LP in a mixture of two solvents, the same qualitative composition varied volumetric ratio of the two solvents and investigated the dependence of the biological effect of compositions of the same qualitative composition from the quantitative content of solvents. The results were compared with the control group who did not receive treatment or prevention, and the control group received the treatment or prevention of LP in the same dose, but given intramuscularly.
Solvent mixture was prepared by volumetric method, mixing the first and second solvents. While both the first and second solvents can consist of a mixture of solvents (N,N-dialkylamino, N-alkylpyridine, terpenes, terpenoids), including mixtures of natural origin - turpentine or essential oils. Preparation of the inventive compositions was carried out by adding known amount of pre-prepared mixture of the first and second solvents to the sample selected LP (in the chemical form of the base) in the vial. The mixture was stirred until complete rest the rhenium LV and used in experiments.
Example 1. Evaluated the preventive effect of dexamethasone in the composition of the inventive transdermal composition for poisoning animals cyclophosphamide (the result of the experiments is depicted in Fig.1).
Preparing a solution of dexamethasone in a mixture solvent concentration of 20 mg/ml Dose of dexamethasone was 10 mg/kg of body weight of the rat. Rats of the control group prevention is not performed. The 28 rats experimental groups transdermal introduced the song with dexamethasone. In the 29-th group of animals was injected intramuscularly injectable dexamethasone in a dose of 10 mg/kg in 15 min after injection of dexamethasone or transdermal compositions with dexamethasone intraperitoneally injected cyclophosphamide at a dose of 600 mg/kg in aqueous solution (10 ml/kg). The animals were observed 2 days, recording the time of death. Expected environments singleton values (M±m, n=6) life expectancy after administration of cyclophosphamide.
In Fig.1 depicts curves of the average life expectancy of animals from high-quality (curves 1-4) the composition of the solvent introduced songs with dexamethasone. The proportion of solvent for each of the 7 groups of animals in each series marked with dots.
Curve 1 in Fig.1 (results marked with squares) corresponds to the composition with dexamethasone containing N,N-dimethylacetamide (the first solvent) and lemon (second solvent, monoterpene) in different concentrations.
Curve 2 in Fig.1 (results marked with circles) corresponds to the composition with dexamethasone containing N,N-dimethylacetamide (first solvent) and terpentine oil (second solvent comprises a mixture of monoterpenes Pimenov and Karen and monoterpenoids) in different concentrations.
Curve 3 in Fig.1 (results marked with triangles) corresponds to the composition with dexamethasone containing N,N-dimethylacetamide (first solvent) and turpentine (second solvent contains crude extract essential oils of coniferous trees, including a mixture of monoterpenes Pimenov and Karen and monoterpenoids) in different concentrations.
Curve 4 in Fig.1 (results marked with black triangles) corresponds to the composition with dexamethasone containing N,N-dimethylacetamide (first solvent) and essential oil of eucalyptus (second solvent comprises a mixture of monoterpenoid cineole with terpenoids) in different concentrations.
In addition, the experimentally determined average life span of rats in the control group who did not receive prophylaxis - she was 6.9±0.4 hours (Fig.1 this is indicated by the arrow y axis), and in the group that received prophylactic dexamethasone intramuscularly at a dose of 10 mg/kg it was 19.8±2,3 including the Statistical significance of the differences is between each of the experimental groups and the control group, and between the 29th of experimental and each of the twenty-eight test groups were evaluated using the criterion of Dunnet; significant difference from control (p≤0,05) shown in Fig.1 marks astrics.
Comparing values of life expectancy of rats who received transdermal oseltamivir composition dexamethasone, and then exposed to the toxicant (curves 1-4 in Fig.1), with the average life expectancy of rats who did not receive prophylaxis (6,9±0,4 h, as indicated by the arrow on the y-axis of Fig.1), clearly shows the prophylactic efficacy of transdermal injection of dexamethasone in the composition of the claimed composition.
When the concentration of N,N-dimethylacetamide in a mixture of more than 16% and up to 99%, inclusive, therapeutic effect was statistically significant; the average duration of life was not different (p≤0,05) from that of intramuscular prophylactic injection of dexamethasone (19,8±2.3 hours). As can be seen from Fig.1, therapeutic effect of TRANS-dermal composition of dexamethasone did not significantly dependent on the qualitative composition of the second solvent (individual monoterpene curve 1, a mixture of terpenes and terpenoids curves 2-4). The average life expectancy of rats that LV was administered prophylactically intramuscular or transdermal in the composition, was significantly higher than that of the animal, not receiving prophylaxis with dexamethasone (6,9±0,4 h, p≤0,05). Animals that LV was administered transdermal or intramuscular injection, did not differ in average life expectancy. Thus, prophylactic transdermal introduction into the body of dexamethasone using the claimed composition was delayed lethal effect of cyclophosphamide in the same way that intramuscular injection of dexamethasone at the same dose.
Example 2. Evaluated the results of treatment with atropine as part of the inventive transdermal composition for poisoning animals phosphorylcholine (the result of the experiments is depicted in Fig.2).
Preparing a solution of the base of atropine in a mixture of solvents concentration of 48 mg/ml Dose of atropine was 24 mg/kg of body weight of the rat. Rats in the thigh muscles of injected solution phosphorylcholine at a dose of 16 mg/kg Animals of the control group was not treated. The 28 rats experimental groups transdermal introduced the song with atropine. In the 29-th group of animals was injected intramuscularly with atropine sulfate at a dose of 24 mg/kg (calculated as base). The animals were observed during the day, and then counted the number of dead. The significance of the differences lethality in experimental groups with mortality in the control was assessed using Fisher's exact test.
In Fig.2 shows the curves lethality in rats that received from the providing phosphorylcholine, from qualitative (curves 1-4) the composition of the solvent introduced songs with atropine. The proportion of solvent for each of the 7 groups of animals in each series marked with dots.
Curve 1 in Fig.2 (results marked with squares) corresponds to the composition with atropine containing N-dimethylacetamide (first solvent) and lemon (second solvent, monoterpene) in different concentrations.
Curve 2 in Fig.2 (results marked with circles) corresponds to the composition with atropine containing N,N-dimethylacetamide (first solvent) and terpentine oil (second solvent comprises a mixture of monoterpenes Pimenov and Karen and monoterpenoids) in different concentrations.
Curve 3 in Fig.2 (results marked with triangles) corresponds to the composition with atropine containing N,N-dimethylacetamide (first solvent) and turpentine (second solvent contains solid extract, essential oils of coniferous trees, including a mixture of monoterpenes Pimenov and Karen and monoterpenoids) in different concentrations.
Curve 4 Of Fig.2 (results marked with black triangles) corresponds to the composition with atropine containing N,N-dimethylacetamide (first solvent) and essential oil of eucalyptus (second solvent comprises a mixture of monoterpenoid cineole with other terpenoids) in different concentric the s.
In addition, experimentally determined the mortality of rats within one day after the introduction of phosphorylcholine in the group who did not receive treatment, it was observed 100% mortality of Fig.2 this is indicated by the arrow y axis), and the mortality of rats in the group treated by intramuscular injection of atropine at a dose of 24 mg/kg (mortality was 0%). The statistical significance of differences in mortality in each experimental group compared with the control assessed using Fisher's exact test, and, in the cases p≤0.05 are shown in Fig.2 marks astrics. The statistical significance of differences in mortality in twenty-eight experimental groups, with mortality rates in the 29-th group evaluated similarly.
As can be seen from the data of Fig.2, applied to the skin the composition of atropine in a mixture of first solvent and a second solvent from the number used (curves 1-4 in Fig.2) increased the survival rate of rats exposed to phosphorylcholine. When the concentration of the first solvent in the composition with atropine containing N,N-dimethylacetamide (first solvent) and lemon (second solvent, monoterpene) from 1% to 99%, or, for other tested compositions with atropine, from 16 to 99%, therapeutic effect was statistically significant and close to therapeutic effect of intramuscular injection of atropine sulfate. Tera is efticiency the effect of transdermal application of atropine did not significantly depended what was the second solvent containing individual monoterpene (curve 1 of Fig.2) or a mixture of terpenes and terpenoids (curves 2-4 in Fig.2), was used for preparation of solvent atropine. Thus, with transdermal administration of atropine in compositions with a volume fraction of the first solvent in the mixture 16-99% survival rate did not differ significantly from that in intramuscular atropine equivalent dose.
Example 3. Evaluated the results of treatment with naltrexone in the composition of the inventive transdermal composition in the administration of fentanyl. The effect of therapeutic action songs recorded by three indicators: the frequency of loss of postural reflex (the result of the experiments is depicted in Fig.3), the term recovery ability of rats to arbitrary movement (the result of the experiments is depicted in Fig.4) and the length of absence of the ability of rats to arbitrary movement (the result is depicted in Fig.5).
Preparing a solution of the base of the naltrexone concentration of 9.6 mg/ml in a mixture of solvents. The dose of naltrexone was 4.8 mg/kg of body weight of the rat. Rats intraperitoneally injected with a solution of fentanyl (toxicant) at a dose of 0.75 mg/kg in the form of a 0.005% solution for injection. Animals of the control group was not treated. Rats 21 experimental group transdermal introduced the composition of naltrexone. In the 22-nd group of animals, the floor is Evesham toxicant, intramuscularly injected naltrexone in the form of a hydrochloric salt at a dose of 5.3 mg/kg, which corresponds to a dose of 4.8 mg/kg) basis.
In Fig.3 reflects the curves of the frequency of cases of loss of postural reflex in rats poisoned by phosphorylcholine, from qualitative (curves 1-3) composition of the solvent introduced songs with naltrexone. The proportion of solvent for each of the 7 groups of animals in each series marked with dots.
Curve 1 in Fig.3 (results marked with squares) corresponds to the composition with naltrexone containing N,N-dimethylacetamide (first solvent) and lemon (second solvent, monoterpene) in different concentrations.
Curve 2 in Fig.3 (results marked with circles) corresponds to the composition with naltrexone containing N,N-dimethylacetamide (first solvent) and terpentine oil (second solvent comprises a mixture of monoterpenes Pimenov and Karen and monoterpenoids) in different concentrations.
Curve 3 in Fig.3 (results marked with triangles) corresponds to the composition with naltrexone containing N,N-dimethylacetamide (first solvent) and turpentine (second solvent comprises a mixture of monoterpenes Pimenov and Karen) in different concentrations.
In the experiment represented in Fig.3, the animals were observed for 8 h by counting the number of rats is Ratusha postural reflex (accepted lateral position). In addition, the experimentally determined frequency of loss of postural reflex rats in the control group, which included animals that had not received treatment with naltrexone (Fig.3 this value, constituting 100% of the arrow y axis), as well as the above figure in the group of rats treated by intramuscular injection of naltrexone (in this group the rate was 0%). Statistical significance of differences in the frequency of cases of loss of postural reflex in the control group and experimental groups were evaluated using Fisher's exact test (F); in the case of p≤0.05 are shown in Fig.3 marks astrics. Statistical significance of differences in the frequency of cases of loss of postural reflex in each 1-21 experimental groups and in the 22nd experimental group was evaluated similarly.
As can be seen from the data shown in Fig.3, applying to the skin a composition with naltrexone in a mixture of two solvents prevented the transition to the lateral position of rats exposed to fentanyl. When the concentration of N,N-dimethylacetamide in a mixture of more than 1% to 99%, inclusive, therapeutic effect was statistically significant and was not materially dependent on any drug containing terpenes (curve 1 in Fig.3), a mixture of terpenes (curve 3 in Fig.3) or a mixture of terpenes and terpenoids (curve 2 in Fig.3), was used for prigotovleniya solvent. With transdermal administration of naltrexone in solutions with a volume fraction of the first solvent in the mixture of from 1% to 99%, the rate of loss of reflex (0%) coincided with one intramuscular injection of naltrexone in an equivalent dose.
To assess therapeutic effect of naltrexone in the composition in a model poisoning animals fentanyl at a dose of 0.75 mg/kg were also registered the term recovery in animals the ability to arbitrary movement of the cage (which is stated in the absence of pace in response to percussion of the tail). The average time interval between application to the skin of rats solution of naltrexone and restore their ability to arbitrary movement shown in Fig.4, and the conditions of poisoning and treatment are similar to those described for Fig.3. In Fig.4 used the same notation of compositions with naltrexone and groups of experimental animals, as in Fig.3. The significance of the differences with the control group in terms of recovery of the ability to arbitrary movement was assessed using the criterion of Gehan-Wilcoxon. Sign astrix noted a significant difference with the control group according to the criterion of Gehenna-test, p≤0,05.
In the absence of treatment the average term recovery of the ability of rats to arbitrary movement was 34.2±3,4 min (M±m, n=6), as indicated by the ordinate of Fig.4 by the arrow. When the content of N,N-dimethylacetamide (first solvent) in the transdermal composition from 1% to 99%, as with intramuscular injection of naltrexone equivalent dose none of the animals exposed to fentanyl, have not lost the ability to arbitrary movement (curves 1-3 in Fig.4).
To assess therapeutic effect of naltrexone in the composition in a model poisoning animals fentanyl at a dose of 0.75 mg/kg were also registered the third indicator of therapeutic efficacy, namely the duration of the absence in animals the ability to arbitrary movement in the cage, which stated that in the absence of pace in response to percussion of the tail, as shown in Fig.5 (experimental conditions described in Fig.3 and Fig.4). In the absence of treatment (control) average duration of absence in rats ability to arbitrary movement was 31.6±12,9 min (M±M, n=6), as indicated by the arrow in the y-axis of Fig.5. In the group of animals after administration of fentanyl received an injection of naltrexone hydrochloride, no animal has lost the ability to arbitrary movement.
As represented by Fig.5, a significant therapeutic effect of the composition with naltrexone was observed in the case for its introduction have used the camping N,N-dimethylacetamide or a mixture of terpenes, containing at least 1% N,N-dimethylacetamide.
Thus, in the case of transdermal injection composition naltrexone, as follows from the joint analysis of all three indicators of recovery model poisoning fentanyl: frequency of loss of postural reflex (the result of the experiments is depicted in Fig.3), term recovery of the ability of rats to arbitrary movement (the result of the experiments is depicted in Fig.4) and the length of absence of the ability of rats to arbitrary movement (the result of the experiments is depicted in Fig.5), transdermal composition naltrexone showed comparable with intramuscular injection of a therapeutic effect when the content of the first solvent is from 1% to 99%.
Example 4. Evaluated the results of treatment with droperidol in experimental acute agitation 2-amino-1-phenylpropane. therapeutic effect was evaluated by the ratio of the number of animal movements in a certain direction after 30 min after treatment with droperidol to the number of movements before the introduction droperidola. The result of the experiment is depicted in Fig.6.
Preparing a solution of the base of droperidol in a mixture of solvents concentration of 5 mg/ml Dose droperidola was 2.5 mg/ kg of body weight of the rat. Rats subcutaneously injected with a solution of 2-amino-1-phenylpropane in a dose of 5 mg/kg in wide,005% solution for injection for modeling of acute agitation. The five rats experimental groups transdermal introduced the song with droperidol. In the sixth experimental group of animals was injected intramuscularly droperidol dose of 2.5 mg/kg Animals of the control group was not treated. Before and 30 min after the introduction of the toxicant and droperidola measured the spontaneous locomotor activity of the animal in an unattended installation for registering movements "Cell activity" (Ugo Basile, Italy).
Built the dependence of the rate of spontaneous motor activity in the vertical (Fig.6 left) and horizontal directions (Fig.6 right) from the mixture of the first (N,N-dimethylacetamide) and second (monoterpene lemon) solvents. The significance of the differences in the number of movements for 3 min with the control group or the group treated with droperidol injection, were evaluated using the nonparametric criterion Mana-Whitney (U). The significance of the differences in the number of movements with the initial level was assessed using non-parametric criterion of Wilcoxon signed (W). Sign astrix noted a significant difference with the control group, p≤0,05, and the pound sign is the significant difference from baseline, p≤0,05. The arrows on the axes of ordinates shows the values in the group who did not receive treatment.
When treating animals with intramuscular droperidola vertical locomotor activity was 11%, and Gori is Antalya - 22% of the original level, which is significantly less than in the control group (p≤0,05). With transdermal administration droperidola significant therapeutic effect was observed in case of dissolution of the LP chose N,N-dimethylacetamide or a mixture of (+)-limonene containing from 1% to 99% N,N-dimethylacetamide. When the concentration of N,N-dimethylacetamide in a solvent mixture of from 1% to 99% of therapeutic effect does not differ materially from those in the group of animals treated with droperidol injection.
Thus, the experimental test composition with LV with different biological activity (steroid anti-inflammatory agent; cholinolytic; antidote drugs opioid series; adjunct) showed the achievement of this goal, namely the implementation of emergency treatment or emergency prevention of the claimed composition with speed and efficiency, comparable with the speed and efficacy of intramuscular injections of the corresponding LP. However, in contrast to previously known compositions intended for emergency or for the prevention of acute conditions, by intramuscular injection, the proposed composition allows you to:
- apply BGN in order of self-help or mutual aid individuals with no skills injections;
- houses in order to avoid contamination of the patient or of other people infectious diseases, blood-borne contact with used syringes or syringe-tubes;
to eliminate the possibility of damage to the main blood vessels and nerves.
1. Composition for transdermal administration of medicinal substances in the organism of man and animals, consisting of a solution of one or more medicinal substances in a mixture of at least two solvents, one of which is N,N-dialkylamino lower carboxylic acid or N-alkylpyridinium General formula
where R2=R1, R1means methyl or ethyl, a R3denotes H, methyl, ethyl,
R1means methyl or ethyl, a R2+R3means trimethylene;
or a mixture of the above N,N-dialkylamino and N-alkylpyridine, and the second solvent is at least one monoterpene or one monoterpenoids or their mixture.
2. The composition according to p. 1, characterized in that the volume ratio of the first and second solvents chosen from about 1/99 to about 99/1.
3. The composition according to p. 1, characterized in that, in the case of use as a medicinal substance droperidola, the volumetric ratio of the first and second solvents chosen from about 1/1 to 99/1.
4. The composition according to p. 1, characterized in that, in the case of use in quality is ve medicinal substance dexamethasone, the volumetric ratio of the first and second solvents chosen from approximately 4/21 to about 99/1.
5. The composition according to p. 1, characterized in that the transdermal input medicinal substances correspond to a kind of pathology or prevention targets.
6. The composition according to p. 1, characterized in that the transdermal input medicinal substance can be a means for emergency care, means acting on the Central or peripheral nervous system, cardiovascular system, urinary system, means influencing the metabolism, the immune system, antimicrobial, antiparasitic and antiviral agents.
7. Dosage form for transdermal administration of medicinal substances, characterized in that it contains a composition according to any one of paragraphs.1-6.
8. Dosage form under item 7, characterized by the fact that made in the form of ointment.
9. Dosage form under item 7, characterized in that in the form of cream.
10. Dosage form under item 7, characterized in that in the form of liniment.
11. Dosage form under item 7, characterized by the fact that is made in the form of a gel.
12. Dosage form under item 7, characterized by the fact that made in the form of an aerosol.
SUBSTANCE: group of inventions relates to therapy, namely to pulmonology, and can be used for suppressing bacteria Pseudomonas aeruginosa, growing in anaerobic conditions, as well as for the treatment of the pulmonary bacterial infection, caused by them. For this purpose an effective quantity of an aerosol of a fluoroquinolone antibiotic, selected from the group, consisting of levofloxacin and ofloxacin, in a concentration of 0.125-0.128 mg/l is introduced.
EFFECT: application of the claimed inventions makes it possible to influence the said bacteria with the quantity of the fluoroquinolone antibiotic, effective of their growth suppression.
22 cl, 3 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to the pharmaceutical industry and represents a composition for the external treatment and prevention of infections caused by the type 1, 2 herpes virus and bacterial complications caused by the herpetic infection, containing lysozyme, peroxidase, povyargol as active ingredients, escin and glycyrrhizinic acid or its salts as anti-inflammatory ingredients, liposomes on the basis of high-active hydrated lecithin in a combination with cholesterol as carriers and pharmaceutically acceptable carriers and excipients, with the ingredients of the composition being taken in certain proportions, wt %.
EFFECT: invention provides extending the range of products for treating and preventing the infections caused by type 1, 2 herpes virus and bacterial complications caused by the herpetic infection.
4 ex, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to pharmaceutics and represents a pharmaceutical composition for parenteral administration containing sub-micron particles of dosocahexaenoic acid ester dispersed in a water phase with the use of mixture of at least two surfactants specified in a) at least one fatty acid polyoxyethylene ester and b) at least one phospholipide derivative, as well as a method for preparing the above pharmaceutical composition.
EFFECT: invention provides higher pharmacological activity.
14 cl, 3 dwg, 3 tbl, 2 ex
SUBSTANCE: method involves preparing a liquid composition containing a pharmaceutical active ingredient, a mixture of solvents containing water, isopropanol in an amount of 5 wt % to 20 wt % and propylene glycol in an amount of 2 wt % to 25 wt %, and a phospholipid foaming agent in an amount of 2 wt % to 25 wt %, foaming the liquid composition mechanically with no propellant used, and measuring the foam volume and stability. That is followed by transforming the nature and/or changing the concentration of the pharmaceutically active ingredient and/or the phospholipid foaming agent and/or changing the concentration of one of the solvents to produce 250 ml of the liquid composition. The above liquid composition is expected to produce foam in the volume of 400 ml and with the stability so that 50% of an initial foam volume is observed so far after the 10-minute hold-up and measured by the standard SITA procedure. The invention also relates to a composition applicable for topical use and prepared by the method described above.
EFFECT: preparing the composition presented by the stable foam.
22 cl, 18 dwg, 1 tbl, 18 ex
SUBSTANCE: stabiliser includes modified chitosan which is obtained by modifying chitosan particles located in an emulsion of an organic solvent - water, with pH 6.0-6.5, by first reacting a mixture consisting of a carboxylic acid in an organic solvent and a condensing agent, and then with an organic base, wherein the carboxylic acid used is either palmitic acid or stearic acid or dodecanoic acid, the condensing agent used is a mixture of hydroxysuccinimide and an aliphatic carbodiimide or formaldehyde and an aliphatic isocyanide, and the organic base used is triethylamine.
EFFECT: effective liposome composition stabiliser which can be obtained using a simple method.
8 cl, 3 tbl, 5 ex, 7 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a carrier applicable for the local drug delivery. A drug is enclosed in a carrier, and the carrier comprises a coating able to release an enclosed drug as a result of a local stimulus. The coating additionally surrounds the contrast agent MR 19F which changes its detectability after being released from the carrier. The invention refers to a method for the drug delivery to an MRT-controlled individual, wherein the method involves administering the above carrier into the individual enabling the carrier releasing the drug, and forming MR 19F images with the use of a contrast produced by the contrast agent MR 19F.
EFFECT: invention enables monitoring the beginning of the drug release from the carrier.
18 cl, 11 dwg, 2 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics and concerns irinotecan liposomes or its hydrochloride containing irinotecan or its hydrochloride, neutral phospholipid and cholesterol, wherein the weight ratio of cholesterol to neutral phospholipid makes 1:3-5, and a method for preparing them.
EFFECT: liposomes have higher stability.
15 cl, 3 dwg, 10 tbl, 10 ex
SUBSTANCE: inhalation aerosol formulation for treating respiratory diseases contains salmeterol or salmeterol xinafoate, fluticasone or fluticasone propionate, a propellent modifier representing perfluorodecalin, and a propellent specified in 1,1,1,2 tetrafluoroethane (HFA-134a) and/or 1,1,1,2,3,3,3-heptafluoropropane (HPA-227ea).
EFFECT: higher respirable fraction and effective pulmonary delivery of the active ingredient; the aerosol has higher stability.
1 dwg, 6 ex
SUBSTANCE: inhalation formulation in the form of aerosol for treating bronchial asthma and chronic obstructive pulmonary disease containing ipratropium bromide monohydrate as an active ingredient, ethanol absolute as a solvent, an aerosol particle size regulator as an adjuvant consisting of triethyl citrate and an acid specified in a group: citric acid, hydrochloric acid, orthophosphoric acid, 1,1,1,4-tetrafluoroethane (HFA-134a) and/or 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea) as a propellant in certain proportions.
EFFECT: increasing the respirable fraction and obtaining an optimised particle size distribution profile.
SUBSTANCE: invention refers to methods of treating a patient suffering from severe and uncontrolled asthma which involve pulmonary administration of a glucocorticoid in the form of a vapour-phase nebulised aerosol in a combination with oral administration of a glucocorticoid. According to one of the declared methods, the nebulised aerosol is administered by inhalation at no more than 20 l/min rate in the total inhalation volume of at least 0.4 l of the vapour phase; t administration of the nebulised aerosol is preceded by administering no more than 150 ml of aerosol-free air. The glucocorticoid is administered in a daily dose of no more than 40 mg of prednisolone and an equivalent dose of another glucocorticoid. The other method of treating the patient involves pulmonary administration of the glucocorticoid in an amount of 400 to 4,000 mcg with using a nebuliser which is used to administer the glucocorticoid aerosol into the lower portion of the lungs at excessive pressure of 40 mbar or less that leads to deposition of more than 200 mcg of the glucocorticoid in the lower portion of the lungs. What is also declared is a method of treating the patient which involves pulmonary administration of the glucocorticoid in the amount of 400 to 4,000 mcg with the aerosol administered by inhalation consisting of three pre-specified periods wherein after the third period, the patient is advised to stop inhaling and exhale; the presented treatment leads to deposition of more than 200 microgram of the glucocorticoid in the lower portion of the lungs.
EFFECT: invention provides improved deposition of the inhaled glucocorticoid in the lower portion of the lungs, min 30% less consumption of oral glucocorticoids and fewer oropharyngeal side effects.
16 cl, 1 ex
SUBSTANCE: invention relates to an antibacterial composition and is intended for the oral cavity care. The antibacterial composition contains an antibacterial system, including a 4-isopropyl-3-methylphenol (IPMP) source of zinc ions and alkali metal C8-18 alkylsulphate and a perorally acceptable carrier or an excipient. The composition Ph constitutes from 5.5 to 7.5.
EFFECT: application of the invention provides the antimicrobial activity.
9 cl, 4 dwg, 3 tbl, 9 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to the pharmaceutical industry and represents a local pharmaceutical composition for treating rosacea containing at least 0.02% berberine or a biologically equivalent berberine analogue, such as palmatine, and an ingredient specified in a group consisting of water, methanol, ethanol and dimethylsulphoxide, wherein berberine or the biologically equivalent berberine analogue represents the major pharmaceutically active ingredient.
EFFECT: invention provides extending the range of products for treating rosacea.
4 cl, 6 ex, 2 dwg
SUBSTANCE: as an antibacterial quinolone compound, a composition contains one of the quinolone compounds, namely lomefloxacin, or norfloxacin, or pefloxacin, or levofloxacin, or sparfloxacine, or moxifloxacin, or gatifloxacin, or gemifloxacin, or their acceptable salts; a preserving agent is paraben esters, or a mixture thereof, or benzalkonium chloride, or cetrimide, or chlorobutanol, or chlorhexidine, and an ointment base in the following proportions, wt %: quinolone compound - 0.05-0.9, preserving agents - 0.0,2, ointment base up to 100. Methods for preparing the composition provide the ointment homogeneity and stability.
EFFECT: group of inventions provides prolonging the period of therapeutic action of the ointment, reducing the dosage frequency.
6 cl, 6 tbl, 32 ex
SUBSTANCE: invention refers to a method of treating recurrent skin and mucosal diseases caused by herpes simplex viruses type 1 and type 2 by coating a damaged region with a preparation containing a base including an active substance - (2,6-dichlorophenyl)amide carbopentoxysulphanic acid of the general formula: wherein X is Na, K, NH4, 2 times a day for 3-5 days, and if observing precursory symptoms, a repeated course of coating with the preparation is performed 1-2 times a day for 2-3 days.
EFFECT: invention provides higher clinical effectiveness in recurrent skin and mucosal diseases caused by herpes simplex viruses type one and type two.
2 cl, 4 ex
SUBSTANCE: ointment consists of emulsion base and pharmacologically active substance. The pharmacologically active substance of the ointment is presented by a fraction having a boiling temperature of 170-215°C (5-6 mm Hg) prepared by yolk pyrolysis on montmorillonite clay at 250-280°C for 20-30 min. The ointment also contains Carbomer, monoglycerides, hydrogenated coconut oil, glycerol, stearic acid, liquid paraffin, ethanol, myristyl myristate, hydrogenated lanolin, butylene glycol, polydimethyl siloxane, dimethicone, Nipagin, Nipasol, and a flavouring agent in certain proportions.
EFFECT: improving wound-healing action.
1 dwg, 1 tbl, 3 ex
SUBSTANCE: invention concerns an ointment composition for reducing hyperkeratosis, softening, stimulating skin regeneration, containing retinol palmitate, α-tocopherol as a stabilising agent, as well as emulsion wax, Vaseline oil, glycerol, ethanol and water.
EFFECT: higher efficacy and stability.
2 dwg, 4 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: pharmaceutical oil-in-water emulsion contains mometasone or mometasone furoate, propylene glycol and water. The propylene glycol concentration makes from 20 to approximately 45 wt %. A mass ratio of propylene glycol and water in the oil-in-water emulsion makes from 1:1 to approximately 1:3. A portion of mometasone or mometasone furoate is found insoluble in the emulsion.
EFFECT: composition is characterised by stability and therapeutic effect.
27 cl, 6 dwg, 5 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of pharmaceutics, in particular represents composition for topic application, which includes, into physiologically acceptable medium at least one derivative of naphthoic acid, benzoylperoxide and at least one film-forming component.
EFFECT: invention is characterised by the fact that said compound of naphthoic acid and benzoylperoxide are in dispersed in said composition form.
23 cl, 14 ex
SUBSTANCE: invention relates to a haemostatic anti-burn and wound-healing composition in the form of a hydrogel, which contains an active gel-forming component, a plasticiser, active and auxiliary components, namely a water-soluble heteropolymer of chitosonium salt in an amount from 1.0 to 10.0 wt %, a dexpanthenol substance and/or a 2-allyloxyethanol substance in an amount from 1.0 to 10.0 wt %, immobilised medicinal substances of aminocaproic or tranexamic acid in an amount from 0.1 to 5.0 wt % and calcium chloride in an amount from 0.05 to 2.0 wt %, immobilised medicinal substances of lidocaine or anylocaine in an amount from 0.1 to 5.0 wt % and chlorhexidine in an amount from 0.005 to 0.1 wt % and water.
EFFECT: extension of exploitation possibilities in stopping external capillary bleedings, local treatment of injured skin, non-healing wounds and local burns.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine and describes a non-aqueous ointment containing a compound of vitamin D, corticosteroid and ester of N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid in Vaseline, optionally containing mineral oil and tocopherol.
EFFECT: ointment is characterised by storage stability and high skin penetration of the corticosteroid.
23 cl, 4 dwg, 5 tbl, 3 ex
SUBSTANCE: described is biomaterial, stimulating the anti-tumour activity, which contains lyophilisate of postnatal induced lymphatic nodes (PNILN) of a patient with cancer. Described is a preparation, stimulating the anti-tumour activity, which contains as an active substance lyophilisate of PNILN of the patient with cancer, and as a solvent, water for injections, cremofor RH-40, an emulsifier T-2, peach oil, glycerol, Kollidon CL-M and benzyl alcohol with the specified component ratio.
EFFECT: obtaining a novel preparation of domestic production, which contains biomaterial, stimulating the anti-tumour activity, possessing the expressed prolonged action, and convenient in application.
3 cl, 5 dwg, 3 ex