Transdermally absorbable formulation containing donepezil

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. What is described is a transdermally absorbable formulation prepared by dissolving donepezil in an adherent plaster base, which contains a hydrophobic polymer and an absorption enhancer. The absorption enhancer represents one substance, or two or more substances specified in lauryl alcohol, triethyl citrate, isopropylmyristate, cetyl lactate, oleyl alcohol, sorbitan monooleate, polyethyleneglycol monostearate, lauromacrogol, N-methyl-2-pyrroldone and triacetin.

EFFECT: transdermally absorbable formulation can administer donepezil stably for a relatively long period of time and can provide both blood donepezil increase, and the properties of sustained release of donepezil.

4 cl, 4 dwg, 6 tbl, 26 ex

 

Area of technology

[0001]

The present invention relates to a transdermally absorbablethe composition, which contains a substrate and an adhesive layer containing an adhesive base and a drug. More specifically, the present invention relates to drug transdermally absorbable composition against dementia, in which the drug is contained as an active ingredient, represents donepezil, which is used for the treatment of dementia.

The level of technology

[0002]

Donepezil is a drug which suppresses the action of acetylcholinesterase, which is widely used to suppress the development of symptoms of dementia when dementia type Alzheimer's disease or the so-called Alzheimer's disease. In Alzheimer's disease, for which I was informed about the failure of the cholinergic system in the brain, acetylcholinesterase inhibitor such as donepezil, increases the amount of acetylcholine in the brain and stimulates the cholinergic system in the brain. Usually examples of currently used formulations of donepezil include oral input, such as tablets, capsules, syrups, granules and injection and rectal administration.

[0003]

However, patients who have progressed to symptomsidentify, it is often difficult to take a drug against dementia. As a dosage form that is suitable for such a case, the patent document 1 describes a transdermal composition and suppository that contains donepezil. However, the patent document 1 is an invention, which mainly refers to the ointments, creams or suppositories that are unstable active ingredient is administered over a long period of time.

In addition, in patent document 2 described cohesive agent containing donepezil, which has a rate of penetration through the skin of at least 1.2 µg/cm2/h or above. However, because the active ingredient is dispersed in the adhesive tape, the properties of the transdermal absorption of the drug, in particular the rapid increase of the level of the drug in the blood after administration, are insufficient.

The list of documents of prior art

Patent document

[0004]

Patent document 1: Japanese Laid patent application Hei. 11-315016

Patent document 2: international patent publication WO 03/032960

Description of the invention

The problem solved by the invention

[0005]

Therefore, to solve standard problems, the objective of the present invention is to provide you with�argasi donepezil transdermal absorbable composition, which can stably enter donepezil over a long period of time and can implement as a property fast improving of donepezil in the blood and property of slow release of donepezil.

In addition, another objective of the present invention is to provide, in transdermally absorbable composition containing the amplifier absorption, high stability transdermally absorbable composition, which prevents the crystallization of the main drug, due to the content of transdermal amplifier absorption, so that donepezil is not crystallized even in conditions of long term storage.

Means of solving the problem

[0006]

To solve these problems, the result of careful study, the authors present invention found that the rate of penetration of drugs through the skin can be increased through the use of a transdermally absorbable composition wherein the donepezil, which is an active ingredient, dissolved in the adhesive base of the patch, which contains a hydrophobic polymer and the amplifier absorption.

In addition, in particular for the composition (hereinafter sometimes herein referred to as "the composition of the ICI"), which contains a block copolymer styrene-isoprene-styrene (sometimes the dal� herein referred to as "SIS") as a base material, the authors present invention also found that the composition, which has high properties of transdermal absorption of a basic drug and are able to consistently release the essential medicine without crystallization of donepezil even under conditions of prolonged storage, may be provided by mixing the ester of hydrogenated rosin and glycerol acting as imparting stickiness means, and donepezil as the main medicinal ingredient in optimal mixing ratio.

In addition, the authors present invention also found that the composition of the SIS crystallization of donepezil can be prevented without reducing the adhesive properties of the composition by optimizing the mixing ratio between the SIS and liquid paraffin, thereby completing the present invention.

[0007]

Therefore, the present invention is a transdermally absorbable composition, which has the following specific composition.

In particular, the main aspects of the present invention are as follows.

(1) the Transdermally absorbable composition obtained by dissolving donepezil, which is an active ingredient in the adhesive base of the patch, which contains a hydrophobic polymer resin� amplifier and absorption.

(2) the Transdermally absorbable composition according to the above (1), where the amplifier removals is one substance or two or more substances selected from lauryl alcohol, triethylcitrate, isopropylmyristate, cutilletta, olejowego alcohol, sorbitanoleat, polietilenglikolmonostearat, lauromacrogol, N-methyl-2-pyrrolidone and triacetin.

(3) the Transdermally absorbable composition according to the above (1) or (2) where the amplifier removals is one substance or two or more substances selected from lauryl alcohol, isopropylmyristate, lauromacrogol and triacetin.

[0008]

Among them is one aspect of the present invention is a composition of the SIS, in particular, contains the following.

(4) the Transdermally absorbable composition obtained by dissolving donepezil, which is an active ingredient in the adhesive base of the patch, which contains a block copolymer styrene-isoprene-styrene, an ester of hydrogenated rosin and glycerol, liquid paraffin and the amplifier absorption.

(5) Transdermally absorbable composition according to the above (4), where the amplifier removals is one substance or two or more substances selected from lauryl alcohol, lauromacrogol and triacetin.

(6) Transdermal absorbable comp�in according to the above (4) or (5), where the mixed amount of the amplifier absorption ranges from 1 to 10 wt%.

(7) Transdermally absorbable composition according to any one of the above (4) to (6), where the mixing ratio between the ester of hydrogenated rosin and glycerol and donepezil is an ester of hydrogenated rosin and glycerol/donepezil = 1.5 to 8.

(8) Transdermally absorbable composition according to any one of the above (4) to (7), where the mixing ratio between the block copolymer styrene-isoprene-styrene and liquid paraffin is a block copolymer of styrene-isoprene-styrene/liquid paraffin = 0.7 to 1.5.

[0009]

Consequently, most specifically, the present invention is as follows.

(9) Transdermally absorbable composition obtained by dissolving from 5 to 30 wt%. donepezil, which is an active ingredient in the adhesive base of the patch, which contains from 5 to 90 wt%. the block copolymer styrene-isoprene-styrene, from 5 to 70 wt%. ester of hydrogenated rosin and glycerol, and 10 to 70 wt%. liquid paraffin, where the mixing ratio between the ester of hydrogenated rosin and glycerol and donepezil is an ester of hydrogenated rosin and glycerol/donepezil = 1.5 to 8, and the ratio of components� of the mixture of block copolymer styrene-isoprene-styrene and liquid paraffin is a block copolymer of styrene-isoprene-styrene/liquid paraffin = 0.7 to 1.5.

[0010]

In addition, as another aspect of the present invention is as follows.

(10) Transdermally absorbable composition obtained by dissolving donepezil, which is an active ingredient in the adhesive base of the patch, which contains an acrylic polymer and, as the amplifier absorption, isopropyl myristate.

(11) Transdermally absorbable composition according to the above (10), where the mixed amount of isopropylmyristate as an amplifier of removals constitutes from 10 to 30% of the mass.

The effect of the invention

[0011]

In accordance with the present invention provided transdermally absorbable composition containing dissolved donepezil, which comprises a hydrophobic polymer and the amplifier absorption.

Using transdermally absorbable composition containing donepezil dissolved, envisaged by the present invention, it is possible to realize the beneficial effects of the rapid increase in the level of donepezil in the blood after the introduction and presentation of effective blood level for a long period of time.

[0012]

In addition, the present invention can provide a composition which exhibits stable properties of the main release of the drug without the occurrence of crystallization of the main drug�public funds even during long-term storage.

[0013]

Hence, according to containing donepezil transdermal absorbable composition provided by the present invention can occur effective absorption of donepezil in the blood stream through the skin. Thus, transdermally absorbable composition has such a beneficial effect that can prevent side-effects from the digestive system that observed with oral administration, and side effects from the nervous system, which can be caused by a sudden increase in the blood level.

Consequently, even for patients with advanced symptoms of dementia, the present invention can provide containing donepezil transdermal absorbable composition that can stably effectively to enter donepezil and which is very effective in the treatment of patients with advanced dementia.

Brief description of the drawings

[0014]

Fig.1 presents a graph that illustrates the results of the nail penetration through the skin of thein vitrotest example 1 of the present invention.

Fig.2 is a graph illustrating the test results for penetration through the skin of thein vitrotest example 2 of the present invention.

Fig.3 is a graph illustrating the test results for penetration through the skin of thein vitrofrom �test of example 3 of the present invention.

Fig.4 is a graph illustrating the results of the test to measure the level of donepezil in the blood of the rabbit for containing donepezil transdermal absorbable composition of the present invention.

Ways of carrying out the invention

[0015]

More detail is described containing donepezil transdermal absorbable composition provided by the present invention.

The term "transdermally absorbable composition" in the present invention relates to an adhesive tape, which comprises at least a substrate and an adhesive composition. The term includes a reservoir type patches for outdoor use, which have a layer of storage of medicines and plasters for external use with a single-layer matrix.

[0016]

Since the patches with a matrix for outdoor use directly glued to the skin using an adhesive composition having samepeople strength of the plaster containing the active ingredient, compared to the reservoir type patches for outdoor use, plasters matrix have superior adhesion properties, as well as more good properties of absorption of the drug.

Therefore, despite the fact that the transdermally absorbable composition according to the present invention mainly about�Isan on the basis of the patch with the matrix as an example, the present invention is not limited to this.

[0017]

Form transdermally absorbable composition provided by the present invention is not specifically limited, provided that the adhesive composition comprises donepezil dissolved in it, and the release of donepezil occurs with a pharmacologically effective rate.

Typically transdermally absorbable composition is formed from a layer of adhesive containing a drug (donepezil) and the substrate material, which is laminated to the rear surface of the layer of adhesive. Preferably, this layer of adhesive had samepeople force that may stick throughout the effective surface area that is sufficient for the treatment on the skin surface for 24 hours or more. However, when it is difficult, you can also use the leaf cover, which has a greater surface area than containing a drug layer, and has an adhesive force.

[0018]

Transdermally absorbable composition according to the present invention may deliver the drug consistently without any problems with adhesion by dissolving donepezil and/or its pharmaceutically acceptable salt in the adhesive composition.

Examples of salts include, but without specific limit, hydrochloride, sulfates, maizy�ATA citrate, fumarate, tartrate, maleate and acetates.

Therefore, in the present invention, the term "donepezil" refers to both donepezil and its pharmaceutically acceptable salts.

In addition, mix the amount of donepezil, based on the total weight of the adhesive composition is from 5 to 30 wt.%, preferably from 5 to 20 wt%. and more preferably from 10 to 20% of the mass.

[0019]

The adhesive composition of the present invention comprises a hydrophobic polymer as an adhesive composition, which has samepeople force.

Despite the fact that the hydrophobic polymer is not specifically limited, it is preferable to use a rubber polymer, an acrylic polymer or silicone polymer.

Examples of the rubber polymer include block copolymer styrene-isoprene-styrene, isoprene, polyisobutylene (hereinafter in this document, "PIB"), a block copolymer styrene-butadiene-styrene (hereinafter in this document, "SBS) and styrene-butadiene rubber (hereinafter referred to herein as a "SBC"). Among them, the ICU is preferred.

[0020]

The acrylic polymer is not specifically limited, provided that it copolymerizate so as to contain at least one kind of (meth)acrylic derivative, the 2-ethylhexylacrylate, methyl acrylate, butyl acrylate, hydroxyethylacrylate, 2-ethylhexyl�the acrylate, etc.

Specific examples include the adhesives described in "Iyakuhin Tenkabutsu 2007 Jiten" (Dictionary of Drug Excipients 2007, Ed. by the Japan Pharmaceutical Excipients Council), such as a copolymer of acrylic acid/octylacrylate, solution of copolymer 2-ethylhexylacrylate/vinyl pyrrolidone, copolymer of acrylate/vinyl acetate, copolymer of 2-ethylhexylacrylate-2-ethylhexylacrylate/datetimeformat, the emulsion copolymer resins, methyl acrylate/2-ethylhexylacrylate and acrylic polymers in solutions of acrylic resins alkanolamines, as well as a series of acrylic adhesives DURO-TAK (manufactured by Henkel Corp.), a series of Eudragit (produced by Higuchi, Inc.) etc.

[0021]

Specific examples of the silicone resin include silicone rubbers such as polyorganosiloxane.

[0022]

Two or more kinds of these hydrophobic polymers can be mixed together for use. Mix the amount of these polymers, taking into account the formation of the layer of adhesive and sufficient permeability, based on the total weight of the composition of these polymers is from 5 to 90 wt.%, preferably from 10 to 80 wt%. and more preferably from 10 to 70 wt%.

[0023]

Preferably, the adhesive composition transdermally absorbable composition provided by the present invention include an amplifier removals. Examples of enhancers of absorption, which can be used include slo�ethyl fatty acid ester, higher alcohol, a surfactant, etc.

Specific examples of the amplifier absorption include meilleure, exellent, triethylcitrate, isopropyl myristate (hereinafter in this document, "IPM"), myristylated, octyldodecanol, tetralite, triacetin, catallactic, laurinlactam, methyl salicylate, glycolicglycolic, etilenglikolevye, diethylbenzene, diisopropylbenzene, the triglyceride fatty acids with medium chain length, lauryl alcohol, stearyl alcohol, isostearoyl alcohol, ministerului alcohol, alerby alcohol, cetyl alcohol, glycerylmonostearate, glycerylmonostearate, glycerylmonostearate, glycerylmonostearate, sorbitanoleat, servicemanual, monolaurate sucrose, Polysorbate 20, propilenglikolmonostearata, polietilenglikolmonostearat, polietilenglikolmonostearat, lauromacrogol, HCO-60, diethanolamides, N-methyl-2-pyrrolidone, Crotamiton, and dimethyl sulfoxide. Preferred are triethylcitrate, isopropyl myristate, catallactic, alerby alcohol, servicemanual, polietilenglikolmonostearat, lauromacrogol, N-methyl-2-pyrrolidone and triacetin.

[0024]

Among them, a composition in which one substance or two or more substances selected from isopropylmyristate, lauromacrogol, lauryl alcohol and triacetin, can exhibit properties of high release of�basic medicines at an initial attach and excellent properties of sustained release of the drug. In particular, when using SIS as the hydrophobic polymer, the effects when combined with lauromacrogols, laurinova alcohol or triacetine, high. In addition, when using the acrylic polymer is preferably used in combination with isopropyl myristate.

[0025]

Considering sufficient permeability of the primary drugs as a composition of plaster and skin irritation, such as redness and swelling, preferred to mix from about 0.01 to 30 wt%. this amplifier removals, based on the total weight of the composition layer of the adhesive. In particular, when using a combination of ICU and of one substance or two or more substances selected from triacetin, lauromacrogol and lauryl alcohol, mix a number of these amplifiers absorption is preferably from 1 to 10 wt%. and more preferably 3 to 8 wt%.

On the other hand, when using a combination of acrylic polymer and isopropylmyristate, mix the number of amplifier absorption is preferably from 10 to 30 wt%. and more preferably from 20 to 30 wt%. If the mixed amount of the amplifier absorption is less than 0.01%, the desired characteristics of the main release of the drug cannot be achieved, whereas if the blend amount �leaves more than 30% wt., experience undesirable effects such as deterioration of properties of the composition or increase skin irritation.

[0026]

The adhesive composition transdermally absorbable composition provided by the present invention may also contain a plasticizer. Examples of plasticizers that can be used include petroleum-based oils (e.g., paraffin of process oil, naphthenic technological oil, aromatic technological oil, etc.), squalane, squalene, vegetable oils (such as olive oil, Camellia oil, tall oil, peanut oil, castor oil, etc.), silicone oil, esters of dibasic acids (e.g., dibutyl phthalate, dioctyl phthalate, etc.), liquid rubber (e.g., polybutene, liquid isoprene rubber, etc.), liquid complex fatty acid ester (isopropyl myristate, exellent, diethylbenzene, diisopropylbenzene, etc.), diethylene glycol, polyethylene glycol, propylene glycol, dipropyleneglycol, etc. Especially preferred is a liquid paraffin, liquid polybutene or silicone oil. Most preferred is a liquid paraffin.

[0027]

Two or more kinds of these components can be mixed together for use. The total mixing amount of such plasticizers based on the total composition layer adhesi�and, considering sufficient permeability through the skin and a sufficient cohesive force as the composition of the tape is 10 to 70 wt.%, preferably from 10 to 60 wt.%, more preferably from 10 to 50 wt%. and even more preferably from 10 to 30% of the mass.

[0028]

It is preferable to admix imparting the adhesiveness of the resin in the adhesive layer of the present invention in order to adjust the adhesive strength of the composition. In addition, some giving the stickiness of the resin show the effect on dissolution of donepezil, so giving such tackifying resin can also be used to adjust the solubility of donepezil in the adhesive.

Examples of imparting stickiness of resins that can be used include derivatives of rosin (for example, rosin, ester of rosin and glycerol, gidrirovannoe rosin, esters of hydrogenated rosin and glycerol ester of rosin and pentaerythritol, etc.), alicyclic saturated hydrocarbon resins (e.g., ARKON P100 production company Arakawa Chemical Industries, Ltd.), aliphatic hydrocarbon resins (e.g., QUINTONE B170 production company Zeon Corporation), terpene resins (e.g., CLEARON P-125 production company Yasuhara Chemical Co., Ltd.), resin maleic acid, etc. From the viewpoint of the adhesive properties of the composition and solubility of donepezil in the composition, CL�iny ester of hydrogenated rosin and glycerol is especially preferred.

[0029]

Mix the amount of giving such tackifying resin, based on the total composition of the adhesive composition, taking into account the sufficient adhesive strength as the adhesive composition, and irritation on the skin during the exfoliation, is from 5 to 70 wt.%, preferably from 5 to 60 wt%. and more preferably from 10 to 50 wt%.

[0030]

Because containing donepezil transdermal absorbable composition provided by the present invention is a transdermally absorbable composition for systemic effects, the crystallization of the main drug during storage can lead to reduced levels of donepezil in the blood, despite the fact that the patch is glued, which is not desirable. Therefore, preferably, the crystals of donepezil were not formed in the structure even under conditions of prolonged storage. However, since the present invention is a composition, which comprises an amplifier transdermal absorption, it is difficult to maintain the homogeneity of the foundations of long stored in the product so that the crystallization of the main drug can occur, due to the increase of heterogeneity framework.

[0031]

Thus for the composition of the SIS attempted to increase the solubility of donepezil, forcing to operate ester HYDR�levers of rosin and glycerol as solubilizer donepezil in addition to functioning as giving the stickiness of the resin. However, when the ester of hydrogenated rosin and glycerol was added in a certain amount or more, see the deterioration of the properties of the main release of the drug due to the fact that the solubility of donepezil becomes too high. Therefore, it is important to mix the ester of hydrogenated rosin and glycerol with a suitable mixing ratio.

[0032]

Based on the research that was conducted by the authors of the present invention, it was found that the preferred ratio of components of the mixture of ester of hydrogenated rosin and glycerol, and in the containing donepezil donepezil transdermal absorbable composition of the present invention is an ester of hydrogenated rosin and glycerol/donepezil = 1.5 to 8, more preferably from 1.5 to 5 and more preferably from 2 to 4. In particular, if an ester of hydrogenated rosin and glycerol/donepezil is less than 1.5, there is a risk of crystallization of the main drug in the composition during storage due to the low solubility of donepezil in the composition, whereas if the ratio is more than 8, deteriorate the properties of the main release of the drug.

[0033]

In addition, also found that there is a relationship between�into mixed number of ICU and crystallization of donepezil in the composition of the ICU. In particular, when the SYSTEM is constrained by the mobility of donepezil in the composition, which means that it is possible to restrain the crystallization of the main drug. However, when contains a large number of ICU, it can also cause deterioration of the adhesive properties of the composition.

On the contrary, mixing of liquid paraffin promotes crystallization of donepezil. In particular, the mixed liquid paraffin, contribute not only to the mobility of donepezil in the composition, but since the liquid paraffin has a low solubility in the donepezil, there is a decrease of solubility of donepezil in the overall composition. However, the reduction of the mixed amount of liquid paraffin leads to deterioration of the adhesive properties.

[0034]

In view of this situation, the present invention makes it possible to restrain the crystallization of donepezil without compromising the adhesion properties by optimizing the mixing ratio between the liquid paraffin and ICI.

In particular, the mixing ratio between the SIS and liquid paraffin in the present invention is a ICU/liquid paraffin = 0.7 to 1.5, and preferably from 0.8 to 1.5. If ICU/liquid paraffin is less than 0.7, mix the amount of liquid paraffin is redundant, so there may be crystallization of donepezil during long-term storage. Another article�Rhone, if ICU/liquid paraffin is more than 1.5, since the content of the SIS is too high, it can cause deterioration of the adhesive force.

[0035]

In transdermally absorbable composition provided by the present invention, optionally you can use an antioxidant, filler, crosslinking agent, preservative and UV absorber.

Preferred examples of the antioxidant include tocopherol and ester derivatives, ascorbic acid, ascorbicacid, nordihydroguaiaretic acid, dibutylaminoethanol (referred to in this document "OSH"), trouble soothing, etc.

Preferred examples of fillers include calcium carbonate, magnesium carbonate, silicates (e.g., aluminum silicate, magnesium silicate, etc.), silicic acid, barium sulfate, calcium sulfate, concat calcium, zinc oxide, titanium oxide, silicon dioxide, etc.

[0036]

Preferred examples of crosslinking means include thermoset resins such as amino resins, phenolic resins, epoxy resins, alkyd resins and unsaturated polyesters, organic crosslinking agents such as isocyanate compounds and isocyanate compounds, and inorganic crosslinking agents such as metals or metal compounds.

Preferred examples of the preservative include AMYLPEROXY�soat, propylparahydroxybenzoate, butylperoxybenzoate, etc.

Preferred examples of the UV absorber include those derived from p-aminobenzoic acid, Anthranilic acid, salicylic acid derivatives, compound amino acid, dioxane derivatives, coumarin derivatives, imidazoline derivatives, pyrimidine derivatives, etc.

[0037]

Antioxidant, filler, crosslinking agent, preservative, ultraviolet absorber, etc. may be mixed in amounts of preferably 10 wt%. or less, more preferably 5% by mass. or less and most preferably 2 wt%. or less based on the total weight of the composition layer of the adhesive composition.

[0038]

Transdermally absorbable composition according to the present invention, which has such a composition as described above, can be obtained by any method. Examples of the method include a method, usually referred to as "hot melt", which contains the drug composition fundamentals heated to dissolution, the dissolved composition framework is applied to remove the film or substrate, and then the resulting object is bonded to the substrate or remove the film; and method, generally referred to as "method with a solvent, which contains a drug component bases are dissolved in a solvent, such as toluene, hexane and ethyl acetate the resulting mixture was dispensed at shooting the film or the substrate, the solvent was removed by drying, and then the resulting object is bonded to the substrate or remove the film.

[0039]

The substrate for transdermally absorbable composition of the present invention may be an elastic or inelastic material. For example, the base material can be selected from the non-woven cloth, polyurethane, polyester, polyvinyl acetate, polyvinylidenechloride, polyethylene, polyethylene terephthalate (hereinafter in this document, "PET"), aluminum sheet, etc. and a composite material of these examples.

[0040]

In addition, the removed film is not specifically limited, provided that the adhesive layer is protected and contained medication against dementia donepezil does not change until until transdermally absorbable composition is not applied to the skin, and provided that the film is coated with silicone so that it can be easy to peel away.

Specific examples include silicone film polyethylene film polyethylene terephthalate or polypropylene film.

[0041]

Thus obtained transdermally absorbable composition according to the present invention is obtained by dissolving the active ingredient donepezil in the adhesive base of the patch, which is mixed hydrophobic polymer, power absorption, and R described above�lichnye supplements. With this line-up appear, the excellent effects of increasing the level of donepezil in the blood after administration and maintaining effective blood levels for a long time.

EXAMPLES

[0042]

Further, the present invention is described in more detail using the following examples of the invention. However, the present invention is not limited to these examples, and the present invention can be various modification within the technical scope of the invention. In addition, in the following examples, unless otherwise indicated, "%" means " wt.%".

[0043]

Example 1

(Formula)

ICU15%
Liquid paraffin24%
OSH1%
Slimy ester of hydrogenated rosin and glycerol35%
Triacetin5%
Donepezil20%
The total number of100%

[0044]

First, donepezil was dissolved in the mixed solution of triacetin and toluene. Then the remaining components�patients under stood, dissolved in toluene, was added to the mixture. Then the mixture was coated remove the foil, and then the toluene was removed by drying. Then covered with removable film was bonded with PET film base, to obtain a transdermal absorbable composition according to the present invention.

[0045]

Examples 2-10

Using the mixture, shown in the following table 1, were obtained transdermally absorbable compositions of examples 2-10 of the present invention, based on the method described in example 1, as described above.

[0046]

Table 1
ComponentExample
12345678910
ICU15161517151515 161717
Liquid paraffin24232423242424232321
OSH1111111111
Ester of hydrogenated rosin and glycerol35353534353535353434
Triacetin5 5
Triethyl citrate5
Isopropyl myristate5
Catallactic5
Polyethylene glycol monolaurate5
Sorbitan monooleate5
Lauromacrogol5
Alerby alcohol5
N-methyl-2-pyrrolidone 52
Donepezil20202020202020202020
Total100100100100100100100100100100

[0047]

Comparative example 1

Transdermally absorbable composition as comparative example 1 was obtained in the same manner as in example 1, except that didn't add amplifier absorption (triacetin).

In addition, the stage were the same as in example 1.

[0048]

Examples 11-21

Using the mixture, are presented in the following table 2, transdermal absorbable compositions of examples 11-21 were obtained based on the method described in example 1, except that the modified mix the amount of donepezil and mix the number of Tria�etina, lauromacrogol and lauryl alcohol as an amplifier of absorption.

[0049]

Table 2
ComponentExample
1112131415161718192021
ICU2222171722222222222222
Liquid paraffin17221719,5172216212717 21
OSH11111111111

Ester of hydrogenated rosin and glycerol4040404040404040404040
Triacetin5557,5
Lauromacrogol 5551
Lauryl alcohol551
Silicon dioxide1
Donepezil151020151510151551515
Total100100100100100100100100100100

[0050]

Example 22

(Formula)

Acrylic adhesive70%
(DURO-TAK 87-2287, manufactured by Henkel Corp.)
IPM10%
Donepezil20%
The total number of100%

[0051]

Transdermally absorbable composition of example 22 of the present invention obtained based on the formula described above, using an acrylic adhesive.

In particular, donepezil, IPM and acrylic adhesive is thoroughly mixed with the solvent (ethyl acetate). The resulting mixture was coated remove the foil, and then the ethyl acetate was removed by drying. Then covered with removable film was bonded with PET film base, to obtain a transdermal absorbable composition according to the present invention.

[0052]Examples 23-25

Transdermal absorbable compositions of examples 23 to 25 of the present invention was obtained in the same manner, as in example 22, based on the formulas given in the following table 3.

[0053]

Example 26

(Formula)

Silicone rubber75%
(BIO-PSA 4601, by Dow Corning Corp.)
Triacetin5%
Donepezil20%
The total number of100%

[0054]

Donepezil, triacetin and the silicone rubber is thoroughly mixed with the solvent (ethyl acetate). The resulting mixture was coated remove the foil, and then the ethyl acetate was removed by drying. Then covered with removable film was bonded with PET film base, to obtain a transdermal absorbable composition of example 26 of the present invention.

[0055]

Comparative example 2

Transdermally absorbable composition as comparative example 2 was obtained in the same manner as in example 22, except that didn't add amplifier absorption (IPM).

The stage was the same as in example 22.

The formulas for examples 22-26 and comparative example 2 together are shown in table 3.

[0056

Table 3
ComponentExampleComparative example
22232425262
Acrylic adhesive7056526480
Silicone rubber75
ICU5
IPM10303010
Lauromacrogol10
Triacetin5
Donepezil201413162020
Total100100100100100100

[0057]

Test example 1

The test for permeability through the skin of hairless rats

To explore the properties of release of the drug donepezil for the composition of the SIS, in particular, the properties of release of donepezil, starting directly from the introduction, when initially attached patch test on the permeability through the skinin vitrocarried out on rats using appropriate transdermal absorbable compositions of examples 1-9 and compare�form of further example 1.

[0058]

[Method]

Was otlivali the skin of the abdomen hairless rats and face of the dermis did facing the side of the receptor layer. The inside was filled with phosphate-saline buffer and the warm water of 37°C was passed through the water jacket.

The respective test compounds attached to a round shape (1,54 cm2and pasted on isecheno the skin. He took samples of the receptor solution in the dynamics, and we calculated the rate of penetration through the skin (mg/cm2/h) in a constant state (8 to 10 hours after start of the test) by measuring the amount of penetration of donepezil, based on high performance liquid chromatography.

[0059]

[Results]

The results are shown in Fig.1.

Based on the results presented in Fig.1, it is confirmed that the compositions of examples 1-9 of the present invention exhibit properties of more rapid release of the drug than the composition of comparative example 1.

[0060]

Test example 2

The test for permeability through the skin in rats

To explore the properties of release of the drug donepezil for the composition of the SIS, in particular the properties of release of donepezil, starting directly from the introduction, when initially attached patch test on the permeability through the skinin vitrowas performed on rats, used a�UY relevant transdermally absorbable compositions of examples 11-13, 15-18, 20 and 21.

[0061]

[Method]

Was otlivali the skin of the abdomen hairless rats and face of the dermis did facing the side of the receptor layer. The inside was filled with phosphate-saline buffer and the warm water of 37°C was passed through the water jacket.

The respective test compounds attached to a round shape (1,54 cm2and pasted on isecheno the skin. He took samples of the receptor solution in the dynamics, and we calculated the rate of penetration through the skin (mg/cm2/h) in a constant state (from 12 to 24 hours after start of the test) by measuring the amount of penetration of donepezil, based on high performance liquid chromatography.

[0062]

[Results]

The results are shown in Fig.2.

Based on the results presented in Fig.2, it is confirmed that the compositions of the respective examples demonstrate the properties of the fast release of the drug. This point also can be confirmed by comparing the speed of penetration through the skin with comparative example 1 of test example 1.

[0063]

Test example 3

The test for permeability through the skin in rats

To explore the properties of release of the drug donepezil for acrylic composition, in particular the properties of release of donepezil, starting directly from the introduction, when�Acelino attached patch the test for permeability through the skinin vitrowas performed on rats, using an appropriate transdermal absorbable compositions of examples 23-25 and comparative example 2.

[0064]

[Method]

Was otlivali the skin of the abdomen of Wistar rats and face of the dermis did facing the side of the receptor layer. The inside was filled with phosphate-saline buffer and the warm water of 37°C was passed through the water jacket.

The respective test compounds attached to a round shape (1,54 cm2and pasted on isecheno the skin. He took samples of the receptor solution in the dynamics and calculated the rate of penetration through the skin (mg/cm2/h) in a constant state (from 12 to 24 hours after start of the test) by measuring the amount of penetration of donepezil, based on high performance liquid chromatography.

[0065]

[Results]

The results are shown in Fig.3.

It is confirmed that the compositions of the respective examples of the present invention exhibit properties of more rapid release of the drug than the composition of comparative example 3.

[0066]

Test example 4

Test to measure the level in the blood of the rabbit

Test to measure the level of donepezil in rabbit plasma was carried out using transdermal absorbable compositions of example 1 and comparative when�EPA 1 (the number of injection drugs 70 mg, respectively).

Each of the patches (transdermal absorbable compositions) pasted on the back of the rabbit, on which the hair was removed, blood was drawn in the dynamics, and measured the levels of donepezil in plasma, based on LC-MS.

The results are shown in table 4.

Based on the results, it is confirmed that the patch (transdermally absorbable composition) in example 1 of the present invention can release the drug longer than the patch (transdermally absorbable composition) of comparative example 1.

[0067]

Test example 5

A stability test of the composition

Following a stability test was performed on the sample of each of the transdermally absorbable compositions of the examples 1, 3, 7, 11, 17, 23 and 24, which was stored for 1 month under conditions of storage at 60°C. These results are shown in table 4.

The test objects consisted of the following.

[0068]

(1) observation of the presence or absence of the precipitation of crystals on the surface of the structure

Each of the stored formulations were observed with respect to the presence or absence of the precipitation of crystals on the surface of the composition visually and with a microscope (C).

The evaluation was performed as follows.

X: Precipitation of crystals can podtverdivshaya.

Δ: Precipitation of crystals can be confirmed using a microscope.

A: Precipitation of crystals cannot confirm.

[0069]

(2) a stability Test of the main drugs

The level of the drug in the formulations of examples 11, 17, 23 and 24, in which the precipitation of crystals were not observed stored in the formulations was measured by liquid chromatography, and coefficient of residual drug (relative %) of each formulation after storage, based on the content of donepezil in every composition before storage as the original value (100%).

[0070]

(3) a stability Test of the main release of the drug

The test for release in the formulations of examples 11, 17, 23 and 24, which were not observed precipitation of crystals stored in the formulations was carried out using the method of USP Drug Release Apparatus 6 (Cylinder) to determine the release rate of donepezil by liquid chromatography.

[0071]

Table 4: test Results on the stability of each composition

[0072]

[0073]

In each of the formulations were stored was no precipitation of crystals, which can be confirmed visually. In particular, in examples 11, 17, 23 and 24, respectively, precipitation of crystals is not observed�of Udall even when observed with a microscope.

In addition, the content of the basic medicines and release properties of the respective compositions of examples 11, 17, 23 and 24 is essentially not worsened and, therefore, found that it was transdermally absorbable preparations which showed excellent stability.

[0074]

Test example 6

Test for primary skin irritation rabbit

Primary skin irritation in examples 11, 13, 18-21, 23 and 24 and commercially available adhesive tape against dementia (Rivastigmine, the content of 9.6 mg) as a control means tested, based on the Draize method using rabbit.

Each test composition was glued within 24 hours to healthy skin on the back of the rabbit and on damaged skin. The condition of the skin was visually determined after 1 h, 24 h and 48 h after separation of the patch, based on the criteria listed in table 5 and calculated stimulation index of each of the test formulations.

The criteria for determining the stimulation index is shown in table 5, and the measurement results are shown in table 6.

[0075]

Table 5
Criteria
Eritrea and crusting AssessmentThe formation of edemaAssessment
No Eritrea0No edema0
Easy Eritrea1Very slight swelling1
Explicit Eritrea2Mild swelling2
Medium to strong Eritrea3Average swelling3
From strong Eritrea to easy formation of a crust4Severe swelling4

[0076]

(1) the stimulation Index was determined based on the following formula.

Stimulation index (SI)=[Total amount of the assessments at 1 and 48 h after separation]/4

(2) Assessment of irritation based on the received stimulation index, as follows:

Evaluation of irritation

SI=0: No irritation

0<SI<2: Mild irritation

2≤SI<5: Average level of irritation

5≤SI: severe irritation

[0077]

Table 6
The test compositionExampleControl drug
1113181920212324
Stimulation index (SI)2,93,03,03,03,02,82,52,53,3

[0078]

Based on the above results, it can be confirmed that transdermally absorbable composition according to the present invention is a highly safe composition, which is as or more secure than commercially available adhesive tape against dementia.

Industrial applicability

[0079]

According containing donepezil transdermal absorbable composition provided by the present invention can occur effective absorption don�Pasila, which is the active ingredient into the bloodstream through the skin.

In addition, it is possible to avoid adverse effects on the digestive system, which was observed after oral administration, and side effects on the nervous system, which can be caused by a sudden increase in the blood level. In addition, the composition, in particular, is effective as a composition for external use, which is intended for long-term administration of donepezil and may shed light on the treatment of dementia.

1. Transdermally absorbable composition obtained by dissolving donepezil, which is an active ingredient in the adhesive base of the patch containing the block copolymer styrene-isoprene-styrene, an ester of hydrogenated rosin and glycerol, liquid paraffin and the amplifier absorption, where
(a) the mixing ratio between the ester of hydrogenated rosin and glycerol and donepezil is an ester of hydrogenated rosin and glycerol/donepezil = 1.5 to 8, and
(b) the mixing ratio between the block copolymer styrene-isoprene-styrene and liquid paraffin is a block copolymer of styrene-isoprene-styrene/liquid paraffin = 0.7 to 1.5, and
where the amplifier removals is one substance or two or more substances, you�early from lauryl alcohol, triethylcitrate, isopropylmyristate, cutilletta, olejowego alcohol, sorbitanoleat, polietilenglikolmonostearat, lauromacrogol, N-methyl-2-pyrrolidone and triacetin.

2. Transdermally absorbable composition according to claim 4, wherein the amplifier removals is one substance or two or more substances selected from lauryl alcohol, lauromacrogol and triacetin.

3. Transdermally absorbable composition according to claim 1 or 2, where the mixed amount of the amplifier absorption ranges from 1 to 10 wt%.

4. Transdermally absorbable composition obtained by dissolving from 5 to 30 wt.%, donepezil, which is an active ingredient in the adhesive base of the patch containing from 10 to 70 wt.%, the block copolymer styrene-isoprene-styrene, 10 to 50 wt.%, ester of hydrogenated rosin and glycerol, and 10 to 60 wt.%, liquid paraffin, where the mixing ratio between the ester of hydrogenated rosin and glycerol and donepezil is an ester of hydrogenated rosin and glycerol/donepezil = 1.5 to 8, and the mixing ratio between the block copolymer styrene-isoprene-styrene and liquid paraffin is a block copolymer of styrene-isoprene-styrene/liquid paraffin = 0.7 to 1.5.

5. Transdermally absorbable composition obtained by solution�ia donepezil, which is the active ingredient in the adhesive base of the patch containing from 10 to 70 wt.%, the block copolymer styrene-isoprene-styrene, 10 to 50 wt.%, ester of hydrogenated rosin and glycerol, and 10 to 60 wt.%, liquid paraffin, where the mixing ratio between the ester of hydrogenated rosin and glycerol and donepezil is an ester of hydrogenated rosin and glycerol/donepezil = 1.5 to 8, and the mixing ratio between the block copolymer styrene-isoprene-styrene and liquid paraffin is a block copolymer of styrene-isoprene-styrene/liquid paraffin = 0.7 to 1.5, and, as the amplifier absorption, isopropyl myristate.

6. Transdermally absorbable composition according to claim 5, where the mixed amount of isopropylmyristate as the amplifier absorption is from 10 to 30 wt%.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts, wherein A is thiazolyl, oxazolyl, thienyl, furyl, imidazolyl, pyrazolyl or oxadiazolyl (structures of which are presented in cl.1 of the patent claim), R1 represents C1-6alkyl; R2 represents (i) phenyl substituted by halogen; C1-6alkyl optionally substituted by morpholine or C1-6dialkylamino; C1-6alkoxy optionally substituted by halogen; or heterocyclyl, wherein a heterocyclyl substitute is specified in morpholine; pyrazolyl optionally substituted by C1-6alkyl; piperidinyl; pyrrolidinyl; oxadiazolyl substituted by C1-6alkyl; furyl substituted by C1-6alkyl; dioxydoisothiazolidinyl; triazolyl; tetrazolyl substituted by C1-6alkyl, tridiazolyl substituted by C1-6alkyl; thiazolyl substituted by C1-6alkyl; pyridyl; or pyrazinyl; (ii) substituted or unsubstituted heterocyclyl specified in quinolinyl; pyridyl substituted by C1-6alkoxy or morpholinyl; or benzo [d] [1, 2, 3] triazolyl substituted by C1-6alkyl; R3 represents phenyl substituted by 2 or 3 substitutes specified in halogen; C1-6alkyl; C1-6alkoxy optionally substituted by halogen; hydroxy group; cyano; or -C(=O)ORa, wherein Ra represents phenyl; R4 represents hydrogen, C1-6alkyl or C1-6halogenalkyl. The invention also refers to a pharmaceutical composition containing the compounds of formula (I), a method for PDE10 inhibition, a method of treating neurological disorders, and to intermediate compounds: 2-(4-chlor-3,5-dimethoxyphenyl)furan and 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzaldehyde.

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39 cl, 13 ex, 2 tbl, 77 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: given invention refers to new 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole derivatives, which can be used for modulating histamine receptors in individuals or for treating neurodegenerative diseases. The above derivatives have formula , wherein R1 is specified in an alkyl, substituted alkoxy or phenyl, and aralalkyl; R2 is specified in an alkyl, C6-C14-aryl optionally substituted by 1 to 5 substitutes specified in alkoxy and alkyl; R3 is an alkyl; and R4 is an alkyl.

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20 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to new quinolin-4-one derivatives of formula (1) or to its pharmaceutically acceptable salt, wherein R1 represents: (1) hydrogen, (2) C1-C6 alkyl, (35) carbamoyl-C1-C6 alkyl optionally containing morpholinyl-C1-C6 alkyl, or (36) phosphonoxy-C1-C6 alkyl optionally containing one or two C1-C6 alkyl groups on a phosphonoxy group; R2 represents: (1) hydrogen or (2) C1-C6 alkyl; R3 represents phenyl, thienyl or furyl, wherein a phenyl ring presented by R3, can be substituted by one C1-C6 alkoxy group; R4 and R5 are bound to form a group presented by any of the following formulas: , , , , , , or a group presented by the following formula: a group optionally containing one or more substitutes specified in a group consisting of C1-C6 alkyl groups and oxogroups; R6 represents hydrogen; and R7 represents C1-C6 alkoxy group. The invention also refers to a pharmaceutical composition based on the compound of formula , to a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method for preparing the compound of formula , as well as to specific compounds.

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18 cl, 1 tbl, 257 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of structural formula (I), which possesses phosphodiesterase 10 inhibitory activity. In formula (I), R1 represents hydrogen, halogen or lower alkyl; the ring A represents optionally substituted 6-10-merous monocyclic or bicyclic heteroaryl containing 1 to 3 nitrogen atoms as heteroatoms, or a group containing a cycloaliphatic 6-merous ring condensed with the above heteroaryl, which is specified in 6-merous cycloalkane and aliphatic 6-merous heterocyclic ring containing an oxygen atom; the ring B represents optionally substituted 4-6-merous monocyclic nitrogen-containing group, which can additionally contain an oxygen atom or a 3-6-merous monocyclic hydrocarbonic group, which can be optionally saturated; R3 represents hydrogen; lower alkyl optionally substituted by a substitute specified in lower alkoxy; or lower cycloalky. The R2,Y radicals, as well as substitutes of the rings A and B are presented in the patent claim.

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20 cl, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present group of inventions refers to medicine, namely to neurology, and concerns treating vegetative-vascular dystonia, dizziness syndrome of various origins, and kinetosis. That is ensured by administering a therapeutic agent containing an activated-potentiated form of brain-specific protein S-100 antibody and using the activated-potentiated form of endothelial NO-synthase antibodies as an additional exalting agent.

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9 cl, 16 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: claimed group of inventions relates to medicine, namely to neurology, and deals with treatment of Alzheimer's disease. For this purpose pharmaceutical composition, which contains activated potentiated form of antibodies to brain-specific protein S-100 and activated potentiated form of antibodies to endothelial NO-synthase, is introduced.

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9 cl, 5 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention represents a liquid dosage form of a hopantenic acid calcium salt possessing nootropic activity, containing an effective amount of the hopantenic acid calcium salt and additive agents. It represents drops, and as additive agents, it contains benzoic acid, sodium saccharinate, an orange flavour, hydrochloric 1M, Trilon B and water.

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2 cl, 4 ex

FIELD: medicine, pharmaceutics.

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5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, chemical-pharmaceutical industry and concerns agents possessing the nootropic and neuromodulatory activity. A tabletted pharmaceutical composition possessingthe nootropic and neuromodulatory activity, characterised by the fact that as an active substance, it contains N-cabamoylmethyl-4-phenyl-2-pyrrolidone; the additives are lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, colloidal silicon dioxide (aerosil) and calcium stearate. The tablets of the composition are prepared by direct compression.

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3 cl, 3 ex

FIELD: medicine.

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9 cl, 5 dwg, 8 ex

FIELD: medicine, pharmaceutics.

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7 cl, 8 tbl, 39 ex

Antiviral agent // 2542488

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to an antiviral agent and aims at inactivating a wide range of viruses. The antiviral agent contains an active agent presented by particles of at least one type of iodide formed by iodine and an element formed in 4-6th periods of the 8-10th or 12-15th groups of the periodic table, Cu or Au. The above element found in the 4-6th periods of the 8-10th or 12-15th groups of the periodic table represents Sb, Ir, Ge, Sn, Tl, Pt, Pd, Bi, Fe, Co, Ni, Zn, In or Hg. What is also presented is the antiviral agent containing particles of at least one type of a cuprous compound as an active ingredient. The above cuprous compound represents chloride, acetate, sulphide, iodide, bromide, peroxide, oxide or thiocyanide.

EFFECT: using the group of inventions provides the agent having the high antiviral activity; the above agent is able to exhibit and maintain its antiviral activity easily since it requires no preparation or special washing.

5 cl, 4 tbl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining adhesive composition without application of solvent, to adhesive composition, which does not contain fillers and is obtained by said method. Method includes a) supply of highly-molecular polyisobutylene (HM PIB) into extruding device, where said HM PIB in fact does not contain fillers, solvents and plasticisers; b) mixing said HM PIB with low-molecular polyisobutylene (LM PIB) in said extruding device to form melt, which in fact does not contain filler, solvents and plasticisers; c) addition of active pharmaceutical ingredient (API) to said melt to obtain API/PIB melt; and d) passing said API/PIB melt through head to form said adhesive composition, which in fact does not contain fillers, solvents and plasticisers.

EFFECT: method of obtaining adhesive composition for production of pressure-sensitive adhesive matrix layers for transdermal delivery of medicinal media without application of inflammable solvents eliminates need in drying blocks, favourably influences environment without any release of solvent, with no undesirable remains of solvent remaining in obtained composition.

21 cl, 4 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine. What is described is a system of the transdermal delivery of a drug containing an effective dose of an antithrombotic agent, such as tirofiban, or its pharmaceutically acceptable salt. A dose of the delivered drug is proportional to an applied plaster size and reaches 60-85% of thrombocyte inhibition. The system enables providing the individualised treatment of patients. There are presented methods of treating various disorders, when the thrombocyte inhibition is required.

EFFECT: transdermal delivery system can deliver the drug to the patient for the prolonged period of time.

25 cl, 12 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to a method for active substance (AS) delivery through an epidermal barrier. The declared method involves using a matrix-type transdermal patch containing a substrate, a protective tape and a polymer layer, and characterised by the fact that 10% PEG-12 dimethicone niosomes are introduced into the polymer layer of the transdermal patch; then the substrate is coated with the polymer layer. The ACs are encapsulated into the niosomes with the use of hemogeniser APV, as well as 10 wt % propylene glycol and 5 wt % isopropyl myristate.

EFFECT: improving the active substance penetration with maintaining the biological activity and prolonging the active substance action.

2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and cosmetology and can be used for the effective transdermal delivery of the wide range of active substances (AS). What is declared is a method for the transdermal delivery of the active substances as a part of PEG-12 dimethicone niosomes characterised by the fact that the AS are included into the niosomes in the concentration of 10% by homogenising gel containing 10% niosomes in the homogeniser APV.

EFFECT: invention provides the higher transdermal effect of the interstitial delivery of the AS as a part of the niosomes.

3 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a method for producing a therapeutic tissue involving producing a polymer base containing alginic acid salt, administering an active substance in a therapeutically effective amount, agitating the mixture in a slow-speed mixer, applying the prepared composition on a textile material containing at least 50% cellulose fibres, while the composition of the polymer with the active substance is applied on the textile material through a mesh template at a cell size of 200 to 450 mcm to generate a continuous polymer layer on the face surface of the textile material not penetrating to the inner side.

EFFECT: method enables extending the range of therapeutic agents and biologically active additives, enabling variation of their concentration that causes their concentration in treating various diseases, enables fast transformation of the technological process and its cost-effectiveness.

28 cl, 23 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and represents a carrier for the delivery of an active agent having the water content of less than 10 wt %, comprising the carrier and a delivery composition containing a carbon matrix, a volatile active agent enclosed into the carbon matrix, and a release agent enclosed into the carbon matrix; the release agent represents a gas specified in carbon dioxide, nitrogen oxide, air, hydrogen sulphide and nitrogen, or an initiating release agent specified in citric acid and bicarbonate, which is initiated by water to form the gas.

EFFECT: invention provides stabilising the volatile agent by the carbon matrix and increasing the effective area of application of the volatile active agent.

11 cl, 3 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine. Described is a method of delivering a medicinal active agent, which includes a stage, at which an individual medicinal product is introduced to a mammal, requiring useful effects for health or treatment of the health state. The product contains one or more filaments, which contain a base material, the medicinal active agent and optionally aesthetic agents, volume-adding means, plasticisers and cross-linking agents.

EFFECT: product is strong during transportation and can contain a wide range of medicinal active agents and aesthetic agents.

37 cl, 6 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and represents toilet paper with the therapeutic properties containing a paper carrier with introduced therapeutic agents in the form of nanoparticles uniformly across the total volume in the weight relation of 1:50 to 1:1000; the therapeutic agents introduced into the dry paper substrate are presented either by a complex of Hamamelis Virginiana in the form of an infusion, or in homeopathic dilutions of 3-6-C, Aesculus Hyppocastanum in the form of an infusion, or in homeopathic dilutions of 3-6-C and Acidum Nitricum in dilutions of 6-12-C, or a complex of Hamamelis Virginiana in the form of an infusion or in dilutions of 3-6-C, Aesculus Hyppocastanum in the form of an infusion in dilutions of 3-6-C, Acidum Nitricum in dilutions of 6-12-C and camomile (Matricaria Chamomilla) in the form of an infusion or in dilutions of 3-6-C.

EFFECT: invention provides the improved preventive and therapeutic properties of the product with simplifying and cheapening the process.

1 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to bioencapsulation, namely to a method for cephalosporin bioencapsulation, wherein poludan is used as a microcapsule coating. The declared method is characterised by adding a cephalosporin powder 0.060 g and the E472 preparation 0.05 g as a surfactant to 1% aqueous poludan 2 g. The prepared mixture is mixed; after the reaction mixture ingredients are dissolved to prepare a transparent solution, carbinol 1 ml as the first precipitation agent, and acetone 5 ml as the second precipitation agent are added drop by drop very slowly. The prepared microcapsule suspension is filtered in a filter, washed in acetone and dried in a drying cabinet; the method is implemented at 25°C.

EFFECT: simplifying and fastening the process of microencapsulation in poludan and higher weight yield.

3 ex

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