Methods for preparing transdermal therapeutic systems based on poly(lactic-co-glycolic acid) (versions)

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine. What is described is a method for preparing a transdermal therapeutic system based on poly(lactic-co-glycolic acid) involving dissolving poly lactide-co-glycolide and a pharmaceutically active substance in an organic solvent, mixing the prepared solution until dissolved completely, hot air drying until dry completely and having a constant weight to prepare a film, cutting the film into sections and packing, with the relation of lactide and glycolide varying within the range of 95:5 to 5:95 (versions).

EFFECT: preparing the transdermal therapeutic system based on poly(lactic-co-glycolic acid) that is biodegradable.

33 cl, 1 dwg, 3 tbl, 6 ex

 

The invention relates to the field of pharmaceutical industry, in particular to methods for transdermal therapeutic systems based on copolymers of lactic and glycolic acids.

Transdermal therapeutic system (TTS) is a dosage form for topical application in the form of plasters, non-woven fabric or film. TTC is capable of continuously and non to Lodge in the body drug (LAN) speeds, giving a flow constant level of drug concentration close to the optimal therapeutic level.

Transdermal therapeutic systems are an alternative to oral and parenteral introduction of medicines. Compared with oral administration, transdermal administration ensures fast action of the drug and helps to avoid reducing his activity as a result of passing through the liver. In addition, with this introduction becomes possible to reduce the frequency of drug administration, to reduce the required dose and avoid fluctuations in its concentration in blood, and the development of adverse reactions - to discontinue the treatment immediately. For some of transdermal drug delivery is the only way of introduction.

The task underlying the creation of this izopet the tion, consists in the further development of transdermal therapeutic systems, the technical result obtained at the solution of this task is to create biodegradable transdermal therapeutic systems based on copolymers of lactide and glycolide.

To achieve this result suggested methods of obtaining transdermal therapeutic system (TTS) based on copolymers of lactic and glycolic acids, the first of which involves the dissolution of a copolymer of lactide-glycolide and pharmacologically active substance in an organic solvent, mixing the resulting solution until complete dissolution, the drying hot air drying and constant weight to obtain the film, cutting the obtained film on parts and packaging; the second involves the dissolution of a copolymer of lactide-glycolide and pharmacologically active substance in an organic solvent, mixing the solution obtained in magnetic stirrer until dissolved, fill the feeder, the feed capillary voltage 5-40 kV, collecting the fibers on the receiving device to produce the non-woven material, the cutting of the obtained non-woven fabric into parts and the packaging; the third variant of the method includes the step of extruding a copolymer of lactide-glycolide with getting the thread and subsequent manufacturing of yarn woven material, the stage of dissolution of the copolymer of lactide-glycolide in an organic solvent, dissolving the pharmacologically active substance, mixing and homogenization of such solutions with the receipt of the final solution, and stage dives in the final solution of a woven material with subsequent cooling and drying; the fourth of declared variants of the method includes dissolving a copolymer of lactide-glycolide in ethyl acetate, adding a pharmacologically active substance in the buffer, mixing, centrifuging the mixture, removing the supernatant by dissolving the precipitate in ethyl acetate, obtaining the suspension and preparation on the basis of the spray.

Preferred, but not mandatory implementation options first, second and third variants of the method involve the ratio of lactide and glycolide be selected in the range from 95:5 to 5:95, preferably 75:25, most preferably 50:50; used as a copolymer of lactide-glycolide-polyethylene glycol (PEG) or - lactide-glycolide-polyvinylpyrrolidone (PVP), where PEG or PVP has a molecular weight of from 400 to 40,000 Da; additional use as plasticizers substances from the group of ε-caprolacton, esters of dicarboxylic acids, glycerin, emulsifiers substances from the group of poloxamer, tween-80 (polyoxyethylene-sorbitan monooleate); DL is the creation of the preset parameters of the release of pharmacologically active substances Aerosil and/or dimethyl sulfoxide, and as the organic solvent is a substance selected from the group comprising dichloromethane, chloroform, methylene chloride, ethyl acetate, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, acetone or mixtures thereof; in addition, the pharmacologically active substance may be a therapeutic or diagnostic agent, while in the case of the pharmacologically active substance is a therapeutic tool, it is chosen from the group including wound healing agent; antimicrobial agents; analgesics and anesthetics local action; anti-inflammatories; trophic factors; drugs for the treatment of addiction and abuse of drugs; drugs for the treatment of addiction and abuse of tobacco; medications to treat addiction and alcohol abuse; hormonal drugs; stimulants; drugs against obesity; cardiotropic means, if the pharmacologically active substance is a diagnostic tool, this tool for the diagnosis of radiation in medicine and/or radiation therapy; it should also be noted that to prevent the change of pH in the acidic side of the first-third variants of the inventive method can further be characterized by the use of wollastonite or bioglass (bioglass 45S5).

Image is etenia is illustrated in figure 1 with the schedule of tissue regeneration.

The ability to reach the desired result due to the fact that the copolymers of lactide and glycolide are biodegradable polymers, chains of which consist of chains of lactic and glycolic acids, the percentage which affects the rate of decomposition and, as a consequence, the release of pharmacologically active substances. Molecule polylactide is optically active D and L-isomers may be present in any ratio, with the exception of the copolymer of L-lactide and D-lactide with relative content links 50/50. The molecular weight of the copolymers may range from 30000 to 100000 Yes (masses were determined by gel permeation chromatography). It is also possible the synthesis of oligomers with a molecular weight of from 2500 to 10000 Da. To improve Biodegradability can be used copolymers containing addition copolymers of polylactide and/or polyglycolides the polyethylene glycol (PEG) of various molecular weights ranging from 400 Da to 40,000 Da.

In General, according to the declared variants of the method, can be obtained transdermal therapeutic system (TTS), based on the copolymer of lactide-glycolide and, if necessary, addition of polyethylene glycol, and/or polyvinylpyrolidone of various molecular weights, and/or plasticizer, and/or surface-activehost, and/or aerosol, and/or dimethyl sulfoxide (DMSO), which added a pharmacologically active substance, in General, such methods are divided into:

method of evaporation of organic solvent;

method electrospinning;

- method of producing composite materials;

- receipt of spray.

Example 1. Obtaining biodegradable TTC by evaporation of the organic solvent.

1.1. Dissolved 195 mg of a copolymer of lactide-glycolide (50:50; M=10000 Da) and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until dissolved, then the solution was dried with hot air until completely dry, then placed in a vacuum Cabinet, dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

1.2. Dissolved 486 mg of a copolymer of lactide-glycolide-ε-caprolactone (71:22:7; M=5000 Da) and 15 mg of the pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until dissolved, then the solution was dried with hot air until completely dry, then placed in a vacuum Cabinet and dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in sterile poly is terenowy bag, which then was sealed.

1.3. Dissolved 972 mg of a copolymer of lactide-glycolide-PEG (50:45:5; M=50000 Yes; MPEG=1000 Yes) and 20 mg of pharmacologically active substances in 60 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until dissolved, then the solution was dried with hot air until completely dry, then placed in a vacuum Cabinet, dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

1.4. Dissolved 972 mg of a copolymer of lactide-glycolide-PEG-ε-caprolactone (70:20:5:5; M=60000 Yes; MPEG1000 Da) and 20 mg of pharmacologically active substances in 100 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until dissolved, then the solution was dried with hot air until completely dry, then placed in a vacuum Cabinet and dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

1.5. Dissolved 195 mg of a copolymer of lactide-glycolide (50:50; M=70000 Yes), 10 mg of glycerol and 10 mg of pharmacologically active substances in 30 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until dissolved, then the solution was dried with hot air until it is fully dry, the donkey which was placed in a vacuum Cabinet and dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

1.6. Dissolved 195 mg of a copolymer of lactide-glycolide (50:50; M=80000 Yes), 20 ml poloxamer 188 and 15 mg of the pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until dissolved, then the solution was dried with hot air until completely dry, then placed in a vacuum Cabinet and dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

1.7. Dissolved 195 mg of a copolymer of lactide-glycolide (50:50; M=90000 Yes), 10 mg of Aerosil and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until dissolved, then the solution was dried with hot air until completely dry, then placed in a vacuum Cabinet and dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

1.8. Dissolved 195 mg of a copolymer of lactide-glycolide (50:50; M=100000 Yes), 10 ml of dimethyl sulfoxide (DMSO) and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until polehereteroy, then the solution was dried with hot air until completely dry, then placed in a vacuum Cabinet and dried residue from acetone to constant weight. The obtained film was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

Example 2. Obtaining biodegradable TTC method electrospinning.

2.1. Was dissolved 1 g of the copolymer of lactide-glycolide (50:50; M=35000 Yes) and 10 mg of pharmacologically active substances in 10 ml of ethyl acetate; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary voltage of 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

2.2. Was dissolved 1 g of the copolymer of lactide-glycolide-ε-caprolactone (75:20:5; M=40000 Da) and 15 mg of the pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary voltage of 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

2.3. Was dissolved 1 g of the copolymer of lactide-glycolide-PEG (50:45:5; M=50000 Yes; MPEG=1000 Yes) and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary voltage of 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

2.4. Was dissolved 1.0 g of a copolymer of lactide-glycolide-PEG-ε-caprolactone (70:20:5:5; M=60000 Yes; MPEG=1000 Yes) and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary voltage of 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

2.5. Was dissolved 1 g of the copolymer of lactide-glycolide (50:50; M=70000 Yes), 0.2 mg of glycerol and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

2.6. Was dissolved 1 g of the copolymer of lactide-glycolide (50:50; M=80000 Yes, 0.2 ml poloxamer 188 and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary voltage of 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

2.7. Was dissolved 1 g of the copolymer of lactide-glycolide (50:50; M=90000 Yes), 0.2 mg of Aerosil and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary voltage of 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

2.8. Was dissolved 1 g of the copolymer of lactide-glycolide (50:50; M=100000 Da), 0.2 ml DMSO and 10 mg is pharmacologically active substance in 10 ml of acetone; the resulting solution was thoroughly mixed on a magnetic stirrer until complete dissolution, was poured into the feeder, filed on capillary voltage of 20 kV and collecting the fibers on the receiving device. The obtained nonwoven fabric was cut into pieces and placed in a sterile polyethylene bag, which was then sealed.

Example 3. Obtaining biodegradable TTC method of composite materials.

3.1. 5 g of a copolymer of lactide-glycolide (50:50; M=50000 Da) was filled in an extruder, heated to 100°C; then at the die exit filament was collected on the drum and on the loom was preparing a woven material.

Dissolved 196 mg of a copolymer of lactide-glycolide (50:50; M=40000 Yes) in 30 ml of chloroform; 10 mg is pharmacologically active substance was dissolved in 4 ml of purified water; mixing the obtained solution and homogenized at 16000 rpm In the resulting solution was lowered woven material produced on the loom and immediately cooled with liquid nitrogen at -196°C. the Obtained composite material is pharmacologically active substances were placed in a freeze drying and dried at -85°C.

3.2. 5 g of a copolymer of lactide-glycolide (75:25; M=50000 Da) was filled in an extruder, heated to 100°C; then at the die exit filament was collected on the drum and on the loom was preparing a woven material.

Dissolved 196 mg of a copolymer of lactide-glycolide (50:50; M=60000 Yes) in 30 ml of chloroform; 10 mg is pharmacologically active substance was dissolved in 4 ml of purified water; mixing the obtained solution and homogenized at 16000 rpm In the resulting solution was lowered woven material and immediately cooled with liquid nitrogen at -196°C. the Obtained composite material is pharmacologically active substance was placed in lyophil the ing the drying and dried at -85°C.

3.3. 5 g of a copolymer of lactide-glycolide-ε-caprolactone (75:20:5; M=70000 Yes fell asleep in the extruder, heated to 100°C; then at the die exit filament was collected on the drum and on the loom was preparing a woven material.

Dissolved 196 mg of a copolymer of lactide-glycolide (50:50; M=80000 Yes) in 30 ml of chloroform; 10 mg pankakoski active substance was dissolved in 4 ml of purified water; mixing the obtained solution and homogenized at 16000 rpm In the resulting solution was lowered woven material and immediately cooled with liquid nitrogen at -196°C. the Obtained composite material is pharmacologically active substances were placed in a freeze drying and dried at -85°C.

3.4. 5 g of a copolymer of lactide-glycolide-PEG (70:25:5; M=90000 Yes; MPEG=1000 Yes) was filled in an extruder, heated to 100°C; then at the die exit filament was collected on the drum and on the loom was preparing a woven material.

Dissolved 196 mg of a copolymer of lactide-glycolide (50:50; M=30000 Da) in 30 ml of chloroform; 10 mg is pharmacologically active substance was dissolved in 4 ml of purified water; mixing the obtained solution and homogenized at 16000 rpm In the resulting solution was lowered woven material and immediately cooled with liquid nitrogen at -196°C. the Obtained composite material is pharmacologically active substances were placed in a freeze drying and dried at -85°C.

3.5. 5 g of a copolymer of lactide-glycolide-PEG-the-caprolactone (70:20:5:5; M=50000 Yes; MPEG=1000 Yes) was filled in an extruder, heated to 100°C; then at the die exit filament was collected on the drum and on the loom was preparing a woven material.

Dissolved 196 mg of a copolymer of lactide-glycolide (50:50; M=30000 Da) in 30 ml of chloroform; 10 mg is pharmacologically active substance was dissolved in 4 ml of purified water; mixing the obtained solution and homogenized at 16000 rpm In the resulting solution was lowered woven material and immediately cooled with liquid nitrogen at -196°C. the Obtained composite material is pharmacologically active substances were placed in a freeze drying and dried at -85°C.

3.6. 5 g of a copolymer of lactide-glycolide (50:50; M=30000 Da), 0.1 g of Aerosil fell asleep in the extruder, heated to 100°C; then at the die exit filament was collected on the drum and on the loom was preparing a woven material.

Dissolved 196 mg of a copolymer of lactide-glycolide (50:50; M=60000 Yes), in 30 ml of chloroform; 10 mg is pharmacologically active substance was dissolved in 4 ml of purified water; mixing the obtained solution and homogenized at 16000 rpm In the resulting solution was lowered woven material and immediately cooled with liquid nitrogen at -196°C. the Obtained composite material is pharmacologically active substances were placed in a freeze drying and dried at -85°C.

4. Getting spray with a pharmacologically active substance on the basis of copolymers mo is full-time and glycolic acids

5 g of a copolymer of lactide-glycolide dissolved in 20 ml of ethyl acetate, add 20 mg farmakologicheskogo substances in the buffer, intensively stirred, the mixture was centrifuged, remove supernatant, the precipitate is dissolved in 40 ml of ethyl acetate, receiving the suspension, on the basis of which prepare the spray is suitable for spraying onto the skin.

For efficacy studies received transdermal therapeutic system in the form of a film, nonwoven fabric, adhesives, containing a copolymer of lactide-glycolide and acexamate acid as a wound healing pharmacologically active substances, simulated wound surface removing the animal fur on the application site of the wound, then with a scalpel cut a piece of leather for panolayou wound size 225 mm2.

For the experiment used adult male Wistar rats weighing 200-250 g in 1 week kept for the purpose of acclimatization in cell groups of 5 animals. Animals were divided into 3 groups of 6 animals in each group:

1 control group; animals with a standard Dolnoslaskie wounds (225 mm2on the side surface of the body, which in the region of the defect does not affect any physical and chemical factors.

group 2 animals with standard Dolnoslaskie wounds (225 mm2on the side surface of the body, which is a region of the defect causing the spray "Panthenol".

group 3 animals with standard Dolnoslaskie wounds (225 mm2on the side surface of the body, which in the region of the defect causing the polymer film containing the copolymer of lactide-glycolide (50:50 M=30000 Da) and acexamate acid in accordance with the stated choice method (figure 1).

Research conducted within 15 days. Daily measured the area of RAS in all the experimental animals. All animals were taken brushstrokes-prints from the surface of wounds after 6, 12 and 24 hours. All animals were biopsy in 5, 10 15 the day with the subsequent production of histological preparations according to standard formulations.

The following examples illustrate the possibility of implementing the claimed TTC with various pharmacologically active substances.

Example 4. Analgesic activity of substances released from TTC.

Test "otdergivanija tail. The animal was placed in an individual plastic camera, the tail was immersed for 5 cm in water with a temperature of 55±1°C. In the test were fixed latent period of deliverance from a painful stimulus is the time period (s)during which the animal pulled the tail out of the water completely. The maximum time presenting a painful stimulus to 30 seconds. The original pain sensitivity was defined as the arithmetic average of the rates recorded at 60, 40, and 20 minutes to the applications TTC. The latent period of deliverance from a painful stimulus was fixed in 20, 40, 60, and 120 minutes after application. Analgesic activity was assessed by the change in the latent period of reaction according to the formula: A=Pop-Lesh where Lpop - latent period disposal after use TTS, Lesch - average latent periods of deliverance to use TTS.

Conducted application SMV males nonlinear albino rats weighing 200-300 g Control animals received the treatment is not conducted. The results are shown in table 1.

Table 1
The test sampleOTDELENIE tail (change the sensitivity, s)
20 min40 min60 min90 min120 min
Control0.5±0.10.5±0.10.3±0.10.2±0.1-0.1±0.1
TTC obtained by the evaporation method1 mg/kg11±1.2* 12.4±1.6*12.8±1.4*6.7±0.7*4.5±0.3*
TTC obtained by the method of electrospinning1 mg/kgof 5.7±0.7*7.5±0.8*5.3±0.6*4.1±0.5*4.3±0.4*
TTC representing a composite material1 mg/kgthe 4.7±0.9*5.2±1.4*4.3±0.7*2.1±0.60.2±0.1
pharmacologically active substance - indometacin10 mg/kg4.2±1.6*3.9±1.2*2.9±1.91.9±1.20.7±0.3
* - significance compared with control at P<0,05.

The presented results suggest that the use TTS causes a significant increase in the latent period of reaction otdergivanija tail in response to pain stimulation.

Example 5. Efficacy trials TTC test the inflammation caused by concanavalin A.

Reacts what I inflammation on the concanavalin a (Con A) is based on the ability of pectin vegetable origin to release mediators of inflammation. Did the applique TTC or have introduced the well-known anti-inflammatory agent in a/b for 20 min to Con A. Con And was introduced subplantar at a dose of 100 μg/20 g of body weight (20 μl of a solution at a concentration of 5 mg/ml), in the contralateral limb, the same volume of saline. After 1 hour, mice were scored, we determined the mass of legs and calculated the index of the reaction of inflammation (Il) according to the formula: IR=(PMAS-RK)*100/RK, where ROP is the mass of the foot hind legs, a pillow which was introduced by Kohn And RK - saline. A statistically significant difference between experimental and control groups in excess of 20%was considered significant (B. I. Lyubimov and others 2000).

Control animals were injected intraperitoneally distilled water. The results are shown in table 2.

Table 2
The test sampleInflammation caused by concanavalin And (index response)
Control16,4±1,5
TTC obtained by the evaporation method10 mg/kg9,2±1,1*
TTC obtained by the method of electrospinning10 mg/kg 13,1±2,4*
TTC representing a composite material10 mg/kg8,7±2,2*
pharmacologically active substance is diclofenac Na10 mg/kg13,7±1,6*
* - significance compared with control at P<0,05.

The results show that the use of anti-inflammatory agent in TTC compared with it in b/W causes a significant decrease in the inflammatory reaction in response to the introduction of concanavalin A.

Example 6. Study of antimicrobial activity as an active ingredient for TTC was taken Chloramphenicol 3% of the Study of antimicrobial activity was performed in accordance with the requirements of the global Fund XI, in vitro method of diffusion in agar. Sterile Petri dishes were placed on a perfectly horizontal surface, poured in 2% mastopathy agar (pH 7.2 to 7.4) in 20 ml of creating an optimal layer thickness equal to 4-5 mm For the types of microbes that do not grow on mesopatamia agar, such as streptococci, pneumococci and other applied 5% blood or serum agar. Before sowing Cup with the environment was dried in a thermostat.

A thick layer of agar was seeded 1-2 ml of the suspension is spicemix microorganisms and triturated with a spatula until a uniform distribution of microorganisms across the surface of the Petri dishes and at the same distance. Excess suspended solids were completely removed, dried for 30 minutes Then the drill bit (d=6 mm) made holes at a distance of 2.5 cm from the wall of the Petri dishes and at equal distances from each other, which are then filled with the studied objects. After the cups were placed in a thermostat at 37°C without turning, horizontally, to form a circular area.

The medicinal substance diffuses from the polymer carrier in agar, forming a drive around the zone of inhibition of growth of sensitive organisms, clearly stand out against the background of continuous growth. After 24 hours was measured diameters of zones of inhibition of growth. The results are shown in table 3.

Table 3
The culture testThe size of stunting in diameter, mm
TTC obtained by the evaporation methodTTC obtained by the method of electrospinningTTC representing a composite materialpharmacologically active substance is chloramphenicol
Staphylococcus aureus 209p201822 21
Staphylococcus aureus Type16141415
Staphylococcus epidermidis Wood-4627253332

Escherichia coli 6751091211
Escherichia paracoli10121211
Proteus vulgaris25202222
Bacillus subtillus L223232423
Bacillus anthracoides 9615131617

The criterion of Kruskal-Wallis P>0,05

More than 10 high activity, 10 - moderate activity, less than 10 - no activity.

1. A method of obtaining a transdermal therapeutic system based on copolymers of lactic and glycolic acids, including the dissolution of the copolymer of lactide-glycolide and pharmacologically active substance in an organic solvent, mixing the resulting solution until complete dissolution, the drying hot air drying and constant weight to obtain the film, cutting the obtained film on parts and packaging, the ratio of lactide and glycolide chosen in the range from 95:5 to 5:95, preferably 75:25, most preferably 50:50.

2. The method according to claim 1, in which is used a copolymer of lactide-glycolide-polyethylene glycol (PEG), where the PEG has a molecular weight of from 400 to 40000 Da.

3. The method according to claim 1, which additionally used as plasticizers substances from the group of ε-caprolacton, esters of dicarboxylic acids, glycerol, polyvinylpyrrolidone different molecular weight.

4. The method according to claim 1, which additionally used as emulsifiers substances from the group of poloxamer, tween-80 (polyoxyethylene-sorbitan monooleate).

5. The method according to claim 1, in which additionally to create the specified parameters release pharmaco is logicheskie active substances are used Aerosil and/or dimethylsulfoxide.

6. The method according to claim 1, in which the organic solvent used substance selected from the group comprising dichloromethane, chloroform, methylene chloride, ethyl acetate, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, acetone or mixtures thereof.

7. The method according to claim 1, wherein the pharmacologically active substance is a therapeutic or diagnostic agent.

8. The method according to claim 7, in which the pharmacologically active substance is a therapeutic agent selected from the group including wound healing agent; antimicrobial agents; analgesics and anesthetics local action; anti-inflammatories; trophic factors; drugs for the treatment of addiction and abuse of drugs; drugs for the treatment of addiction and tobacco abuse; drugs for the treatment of addiction and alcohol abuse; hormonal drugs; stimulants; drugs against obesity; cardiotropic tools.

9. The method according to claim 7, in which the pharmacologically active substance is a diagnostic tool for the diagnosis of radiation in medicine and/or radiation therapy.

10. The method according to any one of claims 1 to 9, which additionally use wollastonite or bioglass to prevent changes in pH in the acidic side.

11. The method of obtaining Tran the dermal therapeutic system based on copolymers of lactic and glycolic acids, including the dissolution of the copolymer of lactide-glycolide and pharmacologically active substance in an organic solvent, mixing the solution obtained in magnetic stirrer until complete dissolution, the feed capillary voltage 5-40 kV, collecting the fibers on the receiving device to produce the non-woven material, the cutting of the obtained non-woven fabric into parts and packaging.

12. The method according to claim 11, in which the ratio of lactide and glycolide selected in the range from 95:5 to 5:95, preferably 75:25, most preferably 50:50.

13. The method according to claim 11, in which is used a copolymer of lactide-glycolide-PEG or PVP, where PEG or PVP have a molecular weight of from 400 to 40000 Da.

14. The method according to claim 11, which further use as plasticizers substances from the group of ε-caprolacton, esters of dicarboxylic acids, glycerin.

15. The method according to claim 11, which further used as emulsifiers substances from the group of poloxamer, tween-80 (polyoxyethylene-sorbitan monooleate).

16. The method according to claim 11, in which additionally to create the specified parameters release of pharmacologically active substances are used Aerosil and/or dimethylsulfoxide.

17. The method according to claim 11, in which the organic solvent used substance selected from the group comprising dichloromethane, chloroform, chloride m is tilen, ethyl acetate tetrahydrofuranate or acetone.

18. The method according to claim 11, in which the pharmacologically active substance is a therapeutic or diagnostic agent.

19. The method according to p, in which the pharmacologically active substance is a therapeutic agent selected from the group including wound healing agent; antimicrobial agents; analgesics and anesthetics local action; anti-inflammatories; trophic factors; drugs for the treatment of addiction and abuse of drugs; drugs for the treatment of addiction and tobacco abuse; drugs for the treatment of addiction and alcohol abuse; hormonal drugs; stimulants; drugs against obesity; cardiotropic tools.

20. The method according to p, in which the pharmacologically active substance is a diagnostic tool for the diagnosis of radiation in medicine and/or radiation therapy.

21. The method according to any of § § 11-20, which further use wollastonite or bioglass to prevent changes in pH in the acidic side.

22. A method of obtaining a transdermal therapeutic system based on copolymers of lactic and glycolic acids, comprising the step of extruding a copolymer of lactide-glycolide with receiving threads and the subsequent manufacturer who tion of threads woven material, the stages of dissolution of the copolymer of lactide-glycolide in an organic solvent, dissolving the pharmacologically active substance, mixing and homogenization of the obtained solutions with the receipt of the final solution and the step of immersion in the final solution of woven material with subsequent cooling and drying.

23. The method according to item 22, in which the ratio of lactide and glycolide selected in the range from 95:5 to 5:95, preferably 75:25, most preferably 50:50.

24. The method according to item 22, in which is used a copolymer of lactide-glycolide-PEG, where the PEG has a molecular weight of from 400 to 40000 Da.

25. The method according to item 22, which is additionally used as plasticizers substances from the group of ε-caprolacton, esters of dicarboxylic acids, glycerin.

26. The method according to item 22, which is additionally used as emulsifiers substances from the group of poloxamer, tween-80 (polyoxyethylene-sorbitan monooleate).

27. The method according to item 22, in which additionally to create the specified parameters release of pharmacologically active substances are used Aerosil and/or dimethylsulfoxide.

28. The method according to item 22, in which the organic solvent used substance selected from the group comprising dichloromethane, chloroform, methylene chloride, ethyl acetate, tetrahydrofuranate or acetone.

29. The method according to item 22, to the m pharmacologically active substance is a therapeutic or diagnostic agent.

30. The method according to clause 29, in which the pharmacologically active substance is a therapeutic agent selected from the group including wound healing agent; antimicrobial agents; analgesics and anesthetics local action; anti-inflammatories; trophic factors; drugs for the treatment of addiction and abuse of drugs; drugs for the treatment of addiction and tobacco abuse; drugs for the treatment of addiction and alcohol abuse; hormonal drugs; stimulants; drugs against obesity; cardiotropic tools.

31. The method according to clause 29, in which the pharmacologically active substance is a diagnostic tool for the diagnosis of radiation in medicine and/or radiation therapy.

32. The method according to any of p-31, which further use wollastonite or bioglass to prevent changes in pH in the acidic side.

33. A method of obtaining a transdermal therapeutic system based on copolymers of lactic and glycolic acids, including the dissolution of the copolymer of lactide-glycolide in ethyl acetate, adding a pharmacologically active substance in the buffer, mixing, centrifuging the mixture, removing the supernatant by dissolving the precipitate in ethyl acetate, obtaining the suspension and cooking to her about the new spray.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to traumatology and orthopaedics, enabling preparing a biologically active preparation of autoblood for enhancing neogenesis processes. The presented technique involves sampling whole blood, centrifuging, selecting a middle layer of plasma so that to avoid the erythrocyte ingress. The centrifuged platelet concentrate is frozen in a cold room at temperature below minus 1 C°, dried for at least three minutes within the temperature range of 2 C° to 52 C°; the lyophilisate is sterilised before use.

EFFECT: technique of platelet-rich plasma lyophilisation enables preserving the TGF PDGF VEGF factor viability min 1,5 months from the moment of blood sampling.

1 tbl

FIELD: medicine.

SUBSTANCE: what is presented is a boric coating containing a barrier material and an adhesive material. The barrier material and adhesive material are applicable for combined or sequential postoperative application on the mucosal tissue. Such application provides a multilayer film dressing containing a layer of the above barrier material and a layer of the above adhesive material contacting with the barrier material and mucosal tissue. The dressing is left unmoved in place for 48 hours after the postoperative application of the multilayer film on the mucosal tissue. The dressing is absorbed for 14 days. The multilayer film dressing has an external rim surrounding a tonsil bed and a concave centre shaped after the tonsil bed.

EFFECT: reducing or eliminating pain sensations following the mucosal operations, including tonsilectomy, adenoidectomy or other pharyngeal operations.

19 cl, 17 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, more specifically to dressings used in general surgery, traumatology, obstetrics, gynaecology, proctology, dentistry for closure and healing of wounds (including post-operative), bed-sores, ulcers, burns, complicated purulent and putrid infections with an evident purulo-necrotic layer. A wound and burn closure and healing dressing containing a wound or burn facing therapeutic layer consisting of a therapeutic and sorption agent that is a layer of paste-like gel of iron or aluminium gel with added graphite carbon at 1 g of the additive per 100 ml of the gel, of the thickness of 0.5 cm providing a sorption ability not less than 10 g/g.

EFFECT: preparing the wound and burn dressing possessing high antimicrobial activity and analgesic characteristics, improved sorption ability and atraumatic properties.

7 tbl, 23 dwg

Wound tissue // 2483755

FIELD: medicine.

SUBSTANCE: invention refers to medicine, to preparing a therapeutic and preventing agent for treating radioreactions accompanying the course of radiotherapy. A wound tissue contains a textile fibre-porous material with a viscose component coated with a polymer and a drug preparation introduced therein; the novel is the fact that it is suggested to use the textile material which is made of flax-viscose fibres in ratio of components of flax:viscose 40 - 70 and 60-30, respectively. The fibre-porous material is prepared by needle suturing and has area density 180 g/m2 - 260 g/m2. The coating polymer is sodium alginate, while the drug preparation is introduced in the concentration of 0.25-30 wt %. The drug preparation coating the suggested flax-viscose carrier is presented by poorly soluble preparations of Furaginum, metronidazole, 5-fluoruracil, antioxidant Mexidol, biologically active substances - propolis, sea buckthorn and blackberry extracts.

EFFECT: presented drug preparation has proved itself to be easy to use, enabling higher clinical effectiveness, increasing a prolongation time.

6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents a sorption plate containing furacilin, differing by the fact that a process for making it involves using the additional excipient therapeutic powdered Kimmeridge clay (blue) Undorovskaya, chitosan solution, dimethylsulphoxide, glycerol, acetic acid and purified water in the following proportions (wt %): furacilin 0.75 - 1.5; dimethylsulphoxide 2.5 - 5.0; blue clay 7.5 - 8.5; 98% acetic acid 1.5 - 3.0; chitosan 2.5 - 4.5; glycerol (7.5 - 8.5); purified water up to 100.0.

EFFECT: invention provides making sorption plates for ensuring wound-healing, anti-inflammatory action in medical practice and higher sorption activity.

9 dwg, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a composition for preparing a polyurethane foam dressing which contains the ingredients in the composition in the following ratio, weight fractions: low-molecular polyesterpolyol No. 1 - 75-90, low-molecular polyesterpolyol No. 2 - 10-25, water - 1.0-2, a foaming agent - 1.0-3.0, an urethane formation catalyst - 0.05-0.3, a co-catalyst - 0.05-0, a foam regulator - 2.0-7.5, a bactericidal additive - 1.0-1.2, aromatic diisocyanate - 30-60.

EFFECT: requiring no additional fixation, the medical dressing is easily applied on a wound surface regardless of a configuration and a size of the injured area, and is formed directly on the patient's wound, providing a sterile surface and an anaesthetic effect; its open porous structure absorbs various wound discharges.

3 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to method of obtaining medical napkin for treatment of wounds and burns. In method of obtaining medical napkin, which includes carrying out textile material padding in solution of medication with the following drying in the air, padding is carried out in solution of sodium alginate polysaccharide with content of 18-22% dimexide, and after drying by method of textile printing water solution of polymer composition containing 18-22% of urea, 5-7% of sodium alginate is applied on textile carrier, with following drying of processed material in the air. Method makes it possible to considerably increase concentration of medication in napkin, considerably extend spectrum of applied medications, including by low-soluble, as it does not require presence of functional groups in medication for immobilisation on functional groups of fibre.

EFFECT: method is simpler in realisation, less durative, does not require additional processing of textile material, ie more manufacturable and economical.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to a therapeutic plaster which can provide injured skin or open wounds with an active substance promoting faster or improved wound healing. The plaster shows the new design features which particularly enable drug substances containing proteins or peptides, e.g. erythropoietin (EPO) to exhibit their wound healing and stimulating action ensured by active substance release from the plaster which is not subject to substantial inactivation by the substances contained in wound secretion, and is not metabolised.

EFFECT: making the therapeutic plaster which can provide injured skin or open wounds with an active substance promoting faster or improved wound healing.

37 cl, 1 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a biodegradable plaster containing at least one bioadhesive layer, and at least one non-bioadhesive layer with the bioadhesive layer containing at least one polyarphon dispersion, and at least one bioadhesive polymer with the polyarphon dispersion containing at least one pharmacologically active substance.

EFFECT: biodegradable plaster can deliver drugs, including poorly water soluble ones.

21 cl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a bandage for pain region processing. The bandage provides cooling and delivery of therapeutic formulations to this region. The bandage comprises a bearing carrier, an interpenetrating network of gel-type dope of polyvinyl alcohol and a cross-linking agent wherein the interpenetrating network is located in the bearing carrier, and at least one additional therapeutic agent.

EFFECT: bandage may be applicable many times on various body parts.

21 cl, 4 dwg, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and chemical-pharmaceutical industry, namely to drug preparations used in various spastic intestinal and pancreatic-biliary conditions, especially in irritable bowel syndrome, and to methods for making them. The drug preparation in the form of an orally dispersible tablet characterised by the fact that it contains a combination of hyoscine butyl bromide and diclofenac or its sodium salt in complex with polacrilin potassium in ratio of diclofenac or its sodium salt and polacrilin potassium of 1:2, and pharmaceutically acceptable additives containing mannitol, aspartame and crospovidone. Polyvinyl pyrrolidone K30, a flavouring agent and anhydrous colloidal silicon dioxide.

EFFECT: tablets have the improved bioavailability of the agent.

2 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a controlled-release active agent carrier. The declared carrier contains a natural or synthetic calcium carbonate with an activated surface whereto an active agent is bound. Natural or synthetic calcium carbonate with the activated surface represents a reaction product of natural or synthetic calcium carbonate with carbon dioxide and one acids wherein carbon dioxide is formed in situ when processed by an acid and or supplied from an external source.

EFFECT: invention also refers to a method for preparing the controlled-release carrier which consists in providing calcium carbonate with the activated surface in the form of a tablet or a powder, providing the active agent in the form of a solution or a suspension, contacting calcium carbonate with the activated surface with the active agent and separating the carrier from excess fluid.

17 cl, 5 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine, and represents a therapeutic composition in the form of an orally dispersed tablet for treating a pain syndrome in smooth muscle spasm characterised by the fact that it contains a combination of hyoscine butylbromide and a non-steroidal anti-inflammatory drug (NSAID) in the therapeutically effective amounts as active ingredients and pharmaceutically acceptable additives.

EFFECT: invention provides the higher efficacy and improved bioavailability of the active ingredient.

5 cl, 6 ex, 1 tbl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical compositions for treating urination disturbance that is a syndrome manifested by frequent urination, urinary incontinence, urine retention, etc. The pharmaceutical composition contains an anticholinergic preparation that is diphenyl-acetic acid tropine ester, and preparations of the other mode of action, including Tamsulosin hydrochloride or calcium channels or baclofen in the form of prolonged release tablets or capsules or transdermal dosage forms (gels, ointments or plasters).

EFFECT: using the invention enables extending the range of therapeutic agents and improving the clinical effectiveness in urination disturbances accompanying a variety of common urological, neurological and gynaecological conditions alongside with improving the quality of life in patients with the urination disturbance.

4 cl, 24 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: controlled release solid preparation contains a combination of (1) an antacid, (2) an immediate release portion containing a proton pump inhibitor, preferentially lansoprazole, and a basic substance, and (3) a delayed release portion comprising a proton pump inhibitor and a pH-independent material.

EFFECT: solid preparation according to the invention shows an increase in gastric pH up to 4 or higher 0,5 h after oral administration into a mammal and a retention time at pH 4 or higher for at least 14 hours a day.

16 cl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmacology, and concerns solid dosage forms of taurine. The dosage forms are applicable in treating type I and II diabetes mellitus, cardiovascular insufficiency and hepatobilliary systems. The dosage forms of taurine contain pharmaceutically acceptable carriers, excipients and additives differing by the fact that such forms have an external coating; as taurine promotors, they contain potassium chloride and N-vinylpyrrolidone copolymer.

EFFECT: solid dosage forms possess the improved pharmacological properties and improved efficacy in cardiovascular insufficiency, diabetes mellitus and hepatobilliary systems.

5 cl, 6 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and chemical-pharmaceutical industry, namely to using ipidacrine as an agent for treating disturbed potency.

EFFECT: pharmaceutical composition of ipidacrine represents a tablet, including a prolonged action tablet, or a solid gel capsule.

4 cl, 4 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents an implanted depot of a therapeutic agent for relieving, preventing or treating pain in a patient in need thereof, containing clonidine in the amount of 1 wt % to 15 wt % of the depot of the therapeutic agent, and at least one biodegradable polymer; the above depot of the therapeutic agent has a surface that provides releasing a peak dose of clonidine in the amount of 5 wt % to 20 wt % of total amount of clonidine in the above depot for 24 hours and releasing the effective amount of clonidine for a period of at least three days; the above polymer has characteristic viscosity 0.45 dl/g to 0.55 dl/g and contains poly(D,L-lactide), while said clonidine contains clonidine hydrochloride.

EFFECT: invention extends the range of products for relieving pain.

9 cl, 2 ex, 5 tbl, 34 dwg

Drug form // 2493830

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to drug form, preferably, to pill for per oral application, for pain treatment with controlled release of pharmacologically active composition (A), which it contains. Drug form contains pharmacologically active composition (A), which is potential for abuse, representing opioid or opioid derivative, and hydrophilic polymer (C). Part of surface of drug form by invention is convex, and the other part of its surface is concave. Drug form has tensile strength B1, at least, 500 H in direction of tension E1 and has tensile strength B2 lower than 500 H in direction of tension E2.

EFFECT: drug form by invention is stable to rupture and stable against abuse.

16 cl, 21 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical engineering, and concerns a combined antituberculous remedy containing isonicotinic acid hydrazide (isoniaside) and 2-benzylbenzimidazole (dibazol), and a polymer carrier that is an interpolymer complex of poly(meth)acrylic acid and polyethylene glycol, as well as a method for preparing it.

EFFECT: antituberculous remedy according to the invention has bacteriostatic and bactericidal action on tuberculosis mycobacteria; it provides the continuous maintainance of the active substance concentration at the therapeutically effective level; it causes no considerable blood variations; it is 2,5 times less toxic than isoniaside, and 10 times more active than isoniaside.

7 cl, 1 dwg, 11 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to pharmaceutics and consists in presenting a pharmaceutical composition applicable for the effective administration of low-molecular drug preparation and polymer compounds, such as peptides and proteins by a method, other than injection, and a method for preparing the given composition. The pharmaceutical composition for transmucosal administration contains (a) a positively or negatively charged drug preparation at pH of the prepared composition, (b) a pharmaceutically acceptable low particle having a size not less than 1 nm and no more than 50 mcm, and (c) a pharmaceutically acceptable coating polymer charged opposite in sign to the drug preparation at the above pH with a particle surface coated with a coating polymer, the drug substance fixed on the surface of the given particle by means of the coating polymer; and the complex is formed by a non-covalent interaction of the given low particle and the coating polymer, and a concurrent electrostatic interaction of the coating polymer and the drug preparation.

EFFECT: group of inventions provides higher stability, as well as control of the transmucosal absorption of the given drug preparation.

17 cl, 8 ex, 13 tbl, 10 dwg

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