Antiinflammatory compositions and methods of application thereof

FIELD: medicine.

SUBSTANCE: composition for skin irritation relief with antiinflammatory properties containing olive leaves extract (Olea Europea) and an antiinflammatory substance containing a combination of sodium cocoyl amino acids, magnesium asparate and potassium asparate taken in a certain parity (versions). Personal hygiene products (versions).

EFFECT: composition and based product exhibit high antiinflammatory properties at rather low amounts.

12 cl, 4 ex

 

The technical FIELD TO WHICH the INVENTION RELATES.

The present invention relates to compositions that can exhibit anti-inflammatory properties and, in particular, to compositions containing a combination of anti-inflammatory substances that can be unexpectedly high synergistic anti-inflammatory properties compared to conventional compositions.

The prior art INVENTIONS

There are various active substances for skin care, suitable for use in compositions for personal hygiene. Examples of such active substances for skin care include olive leaf extract, which has been described as a means of exhibiting antihypertensive and hypoglycemic activity, anti-free radicals in food and cosmetics and anti-inflammatory activity when administered orally (see, for example, Leaf extract of Olea europea rich in oleuropein, a product from it, their application as medicines and composition containing them. Combes, Georges; Escaut, Alexandre. Fr. Demande FR 2507477 Al 19821217, 1982; Gonzales M, et al. Hypoglycemic activity of olive leaf, Planta Med 1992 Dec; 58(6):513-515; Use of an extract from the leaves of Olea Europea as an antiradical agent. Amari, Giorgio. Eur. Pat. Appl. (1999), EP 937455 A1 19990825; Fehri B, et al. Olea europaea L.: stimulant, anti-ulcer and anti-inflammatory effects. Boll Chim Farm (1996)135(1):42-49), Sigesbeckia (sacred grass), which was used as a cure for malaria, rheumatism, renal colic and the quality of the ve funds from trichophytia together with glycerin, sapana, which was used to improve blood circulation and resolve blood stasis and to reduce swelling and ease pain, and feverfew girl recognized by the tool, with significant medicinal properties when taken through the mouth and used as antipyretic. Other active ingredients for skin care include oil extracts, such as an oil extract of Boswellia Serrata (frankincense)oil, described as exhibiting antitumor and protivoastmatichesky properties, oil and oat extract, described as exhibiting anti-inflammatory and antioxidant properties.

Applicants recognize the need to develop combinations of active ingredients for skin care for effective treatment, reduction and/or prevention of inflammation of the skin due to various reasons. Although applicants pay tribute to various recognized active substances which exhibit anti-inflammatory properties, in the General case it is difficult, if not impossible, to predict combinations of these active substances, which will be unexpectedly high synergistic anti-inflammatory activity and are effective in reducing inflammation.

In addition, applicants have discovered that in some applications it may be desirable to use relatively low for the number of active substances from the point of view of value for reducing undesirable color and odor, related with certain active substances, to ensure stability, etc. However, many active substances or their combinations tend to exhibit low efficacy or lack of efficacy when used in such low quantities. Accordingly, applicants have recognized the need for combinations of active substances for skin care, which are similar to the high synergistic anti-inflammatory properties and efficiency, and some combinations that can be effective when used in relatively low quantities.

The INVENTION

Applicants have discovered compositions which satisfy the expected requirements for combinations of active substances for skin care, which exhibit unexpectedly high synergistic anti-inflammatory properties. In addition, applicants have recognized that some such compositions exhibit unexpectedly high anti-inflammatory properties in relatively low quantities.

In accordance with some of the options for implementing the present invention relates to compositions containing (a) anti-inflammatory agents selected from the group consisting of extracts of olive leaf, Holly (Holy grass), wood sapana, pyrethrum girl and combinations of two or more of them, and (b) p is atuomobile substance, including at least one lebonyolithato and at least one salt of metal.

In accordance with some of the options for implementing the present invention relates to personal hygiene, including composition according to the present invention.

In additional embodiments implementing the present invention also relates to methods of treatment/reduction of inflammation and/or redness through contact with the skin, requiring reduction of inflammation, the composition according to the present invention and/or contact with skin that needs reducing inflammation, personal hygiene according to the present invention.

Description of the preferred embodiments

In accordance with some preferred variants of implementation of the present invention relates to compositions containing a) anti-inflammatory agents selected from the group consisting of extracts of olive leaf, Holly (Holy grass), wood sapana, pyrethrum girl and combinations of two or more of them, and (b) an anti-inflammatory agent comprising at least one lebonyolithato and at least one salt of metal. Applicants unexpectedly discovered that the combination of anti-inflammatory substances are synergistic and unexpectedly high protivovospalitel the properties, in particular, compositions according to the claimed invention show anti-inflammatory properties, which are higher, often above about 1.2 times higher than approximately 1.8 times than the total anti-inflammatory properties of the individual active components.

Used in the present description, the term "anti-inflammatory substance" means in the General case, any compound or combination of compounds which, when applied to inflamed skin can reduce this inflammation. Examples of active agents suitable for use in the present invention include olive leaf extract, including any water-soluble and oil-soluble extracts of Olea europea, as well as Holly, wood sapana, pyrethrum girl, and combinations of two or more of them, etc. In some preferred embodiments, the active substance includes olive leaf extract (water-soluble extract, manufactured by B & T srl (Italy, Milan) under the trade name Eurol BT and oil-soluble solution produced by Active Organics), Holly (manufactured by Sederma Edison NJ) and pyrethrum girl (produced Indena, (Milan, Italy)), etc.

Any suitable cosmetically acceptable anti-inflammatory agent, comprising at least one lebonyolithato and at least anusol metal, can be used in the invention. Examples of suitable lipoamino include those that are formed when linking amino acids such as alanine, glycine, glutamic acid, aspartic acid, and chain fatty acids, such as, for example, chains of fatty acids of coconut oil, etc. and their salts. Some preferred limousinedisney include chocolatechocolate (formed by the binding of alanine, glycine, glutamic acid and aspartic amino acids molecules of cocola) and their salts, including sodium, potassium salt, etc. In particular, some preferred limousinedisney include sodium chocolatechocolate. Examples of suitable metal salts include sodium, potassium, calcium, magnesium salts, and combinations of two or more of them, etc. Some preferred metal salt include aspartate, gluconate, glycophosphate etc. Some preferred anti-inflammatory agents contain at least one lebonyolithato and at least one aspartate metal. Some of the more preferred materials contain one or more lebonyolithato and at least two aspartate metal. For example, a particularly preferred anti-inflammatory agent contains a combination of sodium chocolatechocolate, aspartate and magnesium aspartate potassium (combined the AI with their sarcosine), sold by Seppic under the trade name Sepicalm S and Sepicalm S WP.

Any suitable number of (a) anti-inflammatory agents selected from the group consisting of extracts of olive leaf, Holly (Holy grass), wood sapana, pyrethrum girl and combinations of two or more of them ("substance"), and (b) anti-inflammatory agents, including at least one lebonyolithato and at least one salt of metal (substance (b)")can be used in the present invention. In some preferred embodiments, the implementation of these compositions contain from more than 0 to less than 100 wt. percent of substance (a) and from less than 100 to more than 0 wt. percent of substance (b) (as used herein throughout, the term "wt. percentage" means wt. the percentage on the basis of the active substance, based on the total weight of the active substance (a) and (b), unless specifically stated otherwise). In some preferred embodiments, the implementation of the composition contains from about 10 to about 90 wt.% substances (a) and from about 90 to about 10 wt.% substance (b), more preferably from about 20 to about 80 wt.% substances (a) and from about 80 to about 20 wt.% substance (b), and even more preferably from about 40 is about 60 wt.% substances (a) and from about 60 to about 40 wt.% substance (b).

In some preferred embodiments, the implementation of the mass ratio of substances (a) to the ingredient (b) is from about 4:1 to about 1:4. In some other embodiments, the implementation ratio is from about 2:1 to about 1:2, and in other embodiments is preferably approximately 1:1.

Compositions according to the present invention may additionally include any number of different additional anti-inflammatory and other cosmetically active substances in addition to the substance (a) and the substance (b). "Cosmetically active agent" is a compound that has a cosmetic or therapeutic effect on the skin, for example substances for the treatment of wrinkles, acne or skin whitening. In one embodiment, the substance is selected from the group of, but not limited to, consisting of: hydroxy acids, benzoyl peroxide; sulfur resorcinol; D-panthenol; hydroquinone; anti-inflammatory substances; substances, whitening the skin; anti-microbial and anti-fungal substances, such as miconazole, ketoconazole and eluvial; vitamins such as ascorbic acid, Tocopherols and tocotrienols, such as Tocopheryl acetate; retinoids, such as retinol, retinal, the palmitate of retinol, acetate retinol, retinoic acid; hormones such the AK estrogen and dihydroxyanthracene; 2-dimethylaminoethanol; lipoic acid; amino acids such as Proline and tyrosine; lactobionic acid; substances, tanning, such as dihydroxyacetone; dimethylaminoethanol; acetyl-coenzyme A, Niacin, Riboflavin; thiamin; ribose; vectors of electrons, such as NADH and FADH2; plant extracts, such as Ginkgo biloba, aloe Vera and soy; and their derivatives. Examples of hydroxy acids include, but are not limited to, (i) alpha-hydroxy acid such as glycolic acid, malic acid, citric acid and tartaric acid, (ii) beta-hydroxy acids such as salicylic acid, and/or (iii) the PHA. See, for example, European patent Application No 273202. Examples of derivatives of ascorbic acid include, but are not limited to, ascorbyl palmitate, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl phosphate zinc, ascorbyl glucoside, sodium ascorbate, ascorbyl polypeptide. Examples of the hydroquinone derivative include, but are not limited to, arbutin. In some preferred embodiments, the implementation of the composition according to the present invention further comprises one or more Tocopherols and/or esters of tocopherol, such as tocopherol acetate.

Applicants have found that compositions according to the present invention, showing neozed the NGOs high anti-inflammatory properties, can be used with great advantage in any means from those intended for personal hygiene/health care. For example, the present invention can be used in creams, lotions, balms, means for washing, the gels, cosmetic pencils, sprays, ointments, Musso and means of decorative cosmetics. These tools can contain several types of cosmetically acceptable systems of vehicles, including but not limited to the above, single-phase solutions (for example, solutions based on oil), emulsions and gels. The term "cosmetically acceptable topical carrier" means a carrier for topical application, which can include other ingredients, dispersed or dissolved therein, and has an acceptable safety. Personal hygiene items may be intended for use by consumers in skin care, skin care children, women, the treatment of wounds in combination of two or more of such cases and the like, Such means can be designed for various applications, including the application to reduce the appearance of "diaper" dermatitis, acne, anti-aging, protection against UV-radiation, application for softening, moisturizing, a combination of two or more of the above items, etc.

Personal hygienics health care, containing the composition according to the present invention may additionally include any of a variety of substances that are generally accepted for use in vehicles for personal hygiene. For example, can be used one or more anionic, nonionic, amphoteric and/or cationic surfactants, pearlescent or opalescent agents, thickening agents, secondary conditioners, hygroscopic substances, hepatoblastoma substances and additives that improve the appearance, make pleasant to the touch and improve the odor of the compositions, such as colorants, perfumes, preservatives, buffer substances, etc.

Personal hygiene products obtained in accordance with the present invention may contain any reasonable number of presents anti-inflammatory compositions. Applicants unexpectedly found that compositions according to the present invention possess significant anti-inflammatory effects, even when presented in compositions for personal care products in relatively low quantities, such low as 0.02 wt. the percentage of the active substance, or less, based on the total mass of the facilities for personal hygiene (hereinafter used in the present description "of the masses. the percentage composition tool"). Accordingly, facilities for personal hygiene according to the present invention can in order to keep from more than 0 to about 5 wt.% composition means, including from about 0.02 to about 4 wt.% songs in the vehicle, from about 0.1 to about 2 wt.% composition means, and from about 0.1 to about 1 wt.% composition tool. In some preferred embodiments, the implementation of personal hygiene items contain from more than 0 to about 1 wt.% composition tool, more preferably from about 0.02 to about 0.5 wt.% composition tool, and even more preferably from about 0.02 to about 0.1 wt.% composition tool.

The present invention also relates to methods for treating and/or reducing inflammation and/or redness on the skin, caused by any reason, including, but not limited to, various forms of eczema and psoriasis, acne vulgaris or acne rosacea, contact dermatitis and allergic dermatitis, photodermatosis, infections caused by alien organisms, insect bites, physical friction and dryness of the skin. In some embodiments, the implementation of the methods according to the invention include skin contact with a composition comprising an anti-inflammatory agent selected from the group consisting of extracts of olive leaf, Holly (Holy grass), saprovore wood, pyrethrum girl and combinations of two or more of them, and the anti-inflammatory wishes is in, including at least one lebonyolithato and at least one salt of metal. In some other embodiments implementing the present invention relates to methods for treating and/or reduce inflammation on the skin through skin contact, requiring anti-inflammatory treatment, means of personal hygiene, containing the composition according to the present invention.

The composition and/or personal care products according to the present invention can be contacted with the skin through any means, corresponding to the presented methods. For example, compositions and tools can be tapicerki applied on the skin, hair or nails. Preferably, in some embodiments, the implementation of the compositions and/or products are applied tapicerki on the skin.

Applicants have found that the methods according to the invention lead to a decrease in redness and, more generally, to reduce inflammation of the skin more effectively than the compared methods.

EXAMPLES

The invention is additionally illustrated by the following examples, which are intended to be an explanation, but in no way limit the present invention.

Example 1: Determination on RAW 264 cell line macrophages

Mononuclear phagocytes, or macrophages, in large quantities found in the skin and are an important component of the born of the immune response. In skin macrophages are the first cells involved in the recognition and elimination of foreign pathogens such as bacteria through the production of nitric oxide, a potential Pro-inflammatory mediator. Be that as it may, the release of nitric oxide, they may also cause inflammation in the skin and damage to the adjacent skin cells and unregulated production of nitric oxide can cause tissue damage. The ability of olive leaf extract, Sepicalm or combination of olive leaf extract and Sepicalm to influence the inflammatory response was illustrated by their ability to reduce the activation of macrophages in the following analysis.

Cells of the cell line of mouse macrophages (RAW 264) were adjusted for the density of 4×1056cells/ml in DMEM with 10% FBS (American type culture Collection, Manassas, VA) and 100 ál was made in tissue culture in 96-well flat-bottomed Petri dish. Murine macrophage cells were stimulated mcg/ml component of the bacterial cells by lipopolysaccharide (LPS) as a positive control, or in the presence or in the absence of olive leaf extract, Sepicalm or combination of olive leaf extract and Sepicalm. Culture of macrophages were exposed for 24 hours at 37°C the effects of 5% CO2in the presence or in the absence of the samples, then education is their nitrites, stable end product of nitric oxide was studied by Griess assay. The results are expressed as percentage of inhibition of production of inflammatory mediator compared to stimulated control cultures.

RAW 264 Murine macrophages stimulated by LPS

4:1
the analyzed material (concentration)Percentage (%) inhibition of the release
nitric oxide
The ratio Sepicalm: olive leaf extract
The olive leaf extract (0.01 per cent)
Sepicalm (0,01%)
6,5+/-0,0
12,1+/-0,05
The olive leaf extract (0,01%)+ Sepicalm (0,01%)20,9+/-0,02*1:1
The olive leaf extract (0,02%)
Sepicalm (0,02%)
24,5+/-1,2
27,1+/-1,1
The olive leaf extract (0,02%)+ Sepicalm (0,02%)77,2+/-0,1*1:1
Olive leaf (0,005%)
Sepicalm (0,02%)
1,31+/and-0.6
32,1+/and-0.6
Olive leaf (0,005%)+
Sepicalm (0,02%)
39,8+/-1,4*
Sepicalm (0,005%)
Olive leaf (0,02%)
3,26+/-1,5
16,6+/and-0.6
Sepicalm (0,005%)+ olive leaf (0,02%)29,31+/of-2.1*1:4
*= P < 0.05 compared with only olive leaf extract or Sepicalm using unpaired student test

Although the olive leaf extract and Sepicalm have a pronounced individual anti-inflammatory activity, we unexpectedly discovered that the combination of olive leaf extract and Sepicalm significantly more effective in reducing inflammation. Anti-inflammatory activity of the combination of olive leaf extract and Sepicalm, larger than a separate activity in the amount shows that the combination of olive leaf extract and Sepicalm has a synergistic effect.

Example 2: Comparison of augmentation Sepicalm aqueous solution potentiation oil solution of natural extracts in RAW 264 Macrophage cell line.

The ability Sepicalm synergistically enhance the anti-inflammatory activity of aqueous and oil solution of extracts of natural substances was illustrated by the ability to reduce the activation of macrophages in the following analysis.

Murine macrophage cells cell lines (RW 264) were adjusted to a density of 4×105 6cells/ml in DMEM with 10% FBS (American type culture Collection, Manassas, VA) and 100 μl was deposited in tissue culture in 96-well flat-bottomed Petri dish. Murine macrophage cells were stimulated with 0,mcg/ml component of the bacterial cells by lipopolysaccharide (LPS), as absolute control, or in the presence or in the absence of Sepicalm, water-soluble extracts (Sigesbeckia and Cesalpinia), partially water-soluble/partially oil-soluble extracts of feverfew maiden), oil-soluble extracts (Oil Extract of Oats, Oil extract of Boswellia Serrata) or combination of extracts plus Sepicalm. Sigesbeckia, also called the sacred grass, is a water extract (Sederma Edison NJ). In China it is used as a means of malaria, rheumatism, renal colic; in Britain, mainly for the treatment of trichophytia in connection with glycerol. Brazilwood, also called Supanova tree, is a water extract of the dried pith of the wood Cesalpinia fragrant. It is used to improve blood circulation and resolve blood stasis and to reduce swelling and relieve pain. Feverfew girl is water-soluble and oil-soluble components (Indena, Milan, Italy). Tanacetum parthenium - a plant commonly known as feverfew girl, has been known since the middle ages as about latausha significant medicinal properties when oral administration is used as a common means of ingesting, hence its common name. Oil Boswellia extract (Quest Intl, South Plainfield, NJ) also called olibanum, is an oil-resinous gum of a tree, Boswellia Serrata, found in the forests of the dry parts of India. His oily, resinous gum flavored, transparent and brownish yellow in color. The main ingredients of the extract are triterpene acid, and bozvelievi acids, one of which is responsible for anti-edematous and protivoastmatichesky properties of Boswellia Serrata. Oil extract of oats (Dragoco, Totowa, NJ) isolated from oats, Avena sativa, has been used as agents against irritation and as an antioxidant. Culture of macrophages were exposed for 24 hours at 37°C the effects of 5% CO2in the presence or in the absence of the samples, then the formation of nitrite, a stable end product of nitric oxide was studied by Griess assay. The results are expressed as percentage of inhibition of production of inflammatory mediator compared to stimulated control cultures.

RAW 264 Murine macrophages stimulated by LPS

The test substance(concentration)Percentage(%)
inhibition of the release of the ICI nitrogen
Physical solubility
Sepicalm (200 ág/ml)of 10.58±0,7
Sigesbeckia (2 µg/ml)20,2±1,7Water soluble
Sigesbeckia (2 µg/ml) +
Sepicalm (200 ág/ml)
53,9±0,8*
Supanova tree (20 µg/ml)25,9±5,2Water soluble
Supanova tree (20 μg/ml) + Sepicalm (200 ág/ml)66,8±1,3*
Feverfew maiden (80 µg/ml)36,0±1,0Water-soluble/ oil-soluble
Feverfew maiden (80 μg/ml) +
Sepicalm (200 ág/ml)
55,63±1,9*
Oil extract of oats
(50 µg/ml)
8,3±3,6oil-soluble
Oil extract of oats
(50 μg/ml) + Sepicalm (200 ág/ml)
12,5±0,6
Oil Boswellia Serrata extract (50 µg/ml)8,7±3,1oil-soluble
Oil Boswellia Serrata extract (50 μg/ml) + Sepicalm (200 ág/ml)17,55±0,6
*= P < 0.05 compared only with the compound/extract, using paired student test

It was shown that Sepicalm causes a synergistic increase in anti-inflammatory activity of water-soluble extracts (Sigesbeckia and Sapana) and partially water-soluble/partially oil-soluble extracts of feverfew girl), not identified synergistic increase in anti-inflammatory activity of oil-soluble extracts (oil extract of oats, oil extract of Boswellia Serrata). These data demonstrate that Sepicalm may enhance aktivnosti water-soluble extracts and partially water-soluble/partially oil soluble extracts.

Example 3

The study was performed on four Caucasian women with skin 1-3 types on the Fitzpatrick scale. Were not allowed to use lotion/other products on the area intended for the study during the study.

The skin of volunteers was subjected to drying during intensified washing. Studied were aware of the following method of drying of the skin during the 7-day period before the study. This technique was washing both legs (below the knee) with soap "ivory" twice a day. This methodology was followed during the course of the study.

For research evaluation was performed before and 4 hours after application of certain amounts of money. Irritation was also induced in some places on the feet by using techniques of shaving before applying means only 1 and day 3, and evaluated as described above. Two tools were studied; the tool containing the active composition consisting of 1,0% Sepicalm 0.01% of olive leaf and 0.5% Coviox T90 ("active" means), and is identical molded tool-placebo ("placebo"), consisting of only 0.01% olive leaf extract as an anti-inflammatory active substances.

The assessment included determination of reddening of the skin, measured using spectroscopy with diffuse coefficient from which Azania (DRS) to calculate the absorption by oxyhemoglobin.

Percentage change in redness in 4 hours after application of each medicinal product on dry skin.

Day 1Day 2Day 3Day 4
The active ingredient24,65%-37,81%-22,52%-27,13%
SE17,53%8,35%10,04%9,48%
Placebo31,74%-12,68%4,86%of 6.31%
SE27,12%to 12.28%23,59%22,19%

Percentage change in redness in 4 hours after application of each medicinal product on dry skin, irritated skin.

Day 1Day 2Day 3 Day 4
The active ingredientto 7.67%-39,69%-31,78%of 1.13%
SE7,19%11,59%9,79%13,37%
Placebo15,88%-3,86%-1,96%-5,80%
SE23,97%26,25%is 11.39%11,43%

Example 4

The mixture of ingredients that show beneficial synergistic effect, can be introduced into the composition of different types of funds. Tools may include, but is not limited to the above, emulsions, surfactants, can be dry-pill/powder and polymer system. Examples of each type of ingredients of the system and the upper and lower bounds of the interval is also defined.

4A - Emulsion system Leave

Components%wt./wt. the interval song
the lower borderthe upper boundary
The aqueous phase is water/thickener/surfactant, all other water-soluble ingredients30,000098,0000
The oil phase/softening agent, wax, fatty alcohols, surfactants, all other oil soluble/miscible ingredients2,000070,0000
Solids to improve the appearance, feel and protection of the skin0,001015,0000
The olive leaf extract0,00010,7500
Sodium chocolatechocolate, sarcosin, potassium aspartate, magnesium aspartate, propylene glycol, water0,005010,0000
Additional natural derived/obtained from natural sources ingredients with known useful properties for extra effect0,005010,0000

4B is a System of surface-active substances - Washable

Components%wt./wt. the interval song
the lower borderthe upper boundary
The aqueous phase is water/thickener/surfactant2,000098,0000
The oil phase/softening agent, waxes, fatty alcohols, surfactants2,000098,0000
Solids to improve the appearance, feel and protection of the skin0,001015,0000
The olive leaf extract0,00010,7500
Sodium chocolatechocolate, sarcosin, potassium aspartate, magnesium aspartate, propylene glycol, water0,005010,0000
Additional natural derived/obtained from natural sources ingredients with known useful properties for extra effect0,005010,0000

4C - System surface-active substances (solid)

Components%wt./wt. the interval song
the lower borderthe upper boundary
Soap base1,000099,0000
Surface-active basis (not containing soap)1,000099,0000
softening/skin conditioners0,050010,0000
odorants0,00002,0000
Disodium EDTA0,01001,0000
Distilled water0,000010,0000
The olive leaf extract0,00010,7500
Sodium chocolatechocolate, sarcosin, potassium aspartate, magnesium aspartate, propylene glycol, water0,005010,0000
Additional natural derivative/receiving the data from a natural source ingredients with known useful properties for extra effect 0,005010,0000

4D - Polymer system is a Leave - in or rinse-off

Components%wt./wt. the interval song
the lower borderthe upper boundary
The aqueous phase is water/thickener15,000098,0000
The oil phase/softening agent, waxes, fatty alcohols2,000085,0000
Polymer systems1,000010,0000
Solids to improve the appearance, feel and protection of the skin0,001015,0000
The olive leaf extract0,00010,7500
Sodium chocolatechocolate, sarcosin, potassium aspartate, magnesium aspartate, propylene glycol, water0,005010,0000
Additional natural proizvodi the e/obtained from natural sources ingredients with known useful properties for extra effect 0,005010,0000

4E Powder or tablets - Insoluble or Soluble

Components%wt./wt. the interval song
the lower borderthe upper boundary
Corn starch0,500099,0000
Talc0,500099,0000
The diluent/filler/carrier0,000025,0000
Binder/sintering substance0,000040,0000
Lubricant0,000010,0000
Disintegrant0,000025,0000
Solids to improve the appearance, feel and protection of the skin0,001015,0000
The olive leaf extract 0,00010,7500
Sodium chocolatechocolate, sarcosin, potassium aspartate, magnesium aspartate, propylene glycol, water0,005010,0000
Additional natural derived/obtained from natural sources ingredients with known useful properties for extra effect0,005010,0000

4F - Anhydrous tool

Components%wt./wt. the interval song
the lower borderthe upper boundary
Liquid @25 ° C, soluble in water ingredients, i.e. esters, mineral oil, soybean oil, etc.0,0199,9900
Liquid 0-S, poorly soluble in water ingredients099,0000
Self emulsifiable waxes015,0000
Hygroscopic substance0,05/td> 3,0000
Flavor/fragrances0,310,0000
The olive leaf extract0,00010,7500
Sodium chocolatechocolate, sarcosin, potassium aspartate, magnesium aspartate, propylene glycol, water0,005010,0000
Additional natural derived/obtained from natural sources ingredients with known useful properties for extra effect0,005010,0000

The tools described in examples 4A-4F are made via the following methods (techniques):

Manufacturing instructions for the systems containing oil and water:

1) combine the ingredients of the aqueous phase, mixing and heat to homogeneity;

2) combine oil phase ingredients, mix and heat to homogeneity;

3) then add the oil phase to the aqueous phase at the same temperature of both phases, with stirring;

4) mix until smooth, homogenize if necessary;

5) add preservatives and fragrances after cooling.

Manufacturing instructions to be the water systems:

1) first, place all the ingredients into the pot;

2) to heat with stirring until a homogeneous phase;

3) pour in forms or packaging and allow to cool.

1. Composition for reducing skin irritation with anti-inflammatory properties, containing (a) an anti-inflammatory agent, representing the olive leaf extract (Olea Europea), and (b) an anti-inflammatory agent containing a combination of sodium chocolatechocolate, asparate magnesium and asparate potassium ratio of ingredient (a) to ingredient (b) is approximately 4:1.

2. The composition according to claim 1, where the specified composition further comprises one or more Tocopherols.

3. A means of personal hygiene, containing the composition according to claim 1.

4. A means of personal hygiene according to claim 3, containing the specified composition in an amount of from about 0.02 to about 1 wt.% composition tool.

5. A means of personal hygiene according to claim 4, containing the specified composition in an amount of from about 0.02 to about 0.1 wt.% composition tool.

6. A means of personal hygiene according to claim 5, additionally containing tocopherol.

7. A means of personal hygiene to reduce the irritation of the skin containing composition with anti-inflammatory properties, containing (a) an anti-inflammatory agent, representing the olive leaf extract (Olea Europea) and (b) about iloveparishilto substance, containing a combination of sodium chocolatechocolate, asparate magnesium and asparate potassium, and the ingredient (a) and ingredient (b) is represented in the specified composition in a ratio of about 4:1.

8. A means of personal hygiene to reduce the irritation of the skin containing composition with anti-inflammatory properties, containing (a) an anti-inflammatory agent, representing the olive leaf extract (Olea Europea), and (b) an anti-inflammatory agent containing a combination of sodium chocolatechocolate, asparate magnesium and asparate potassium, and the ingredient (a) and ingredient (b) is represented in the specified composition in a ratio of about 1:4 of the anti-inflammatory composition is present in the means of personal hygiene in amount from greater than 0 to about 5 wt.% composition in the product.

9. A means of personal hygiene according to claim 7, where the specified composition with anti-inflammatory properties present in the means of personal hygiene in an amount of more than 0.02 to about 0.5 wt.% composition in the product.

10. A means of personal hygiene according to claim 7, where the specified composition with anti-inflammatory properties present in the means of personal hygiene in an amount of more than 0.02 to about 0.1 wt.% composition in the product.

11. Composition for reducing skin irritation, containing (a) p is atuomobile substance, contains olive leaf extract (Olea Europea), and (b) an anti-inflammatory agent containing a combination of sodium chocolatechocolate, asparate magnesium and asparate potassium, and the ingredient (a) and ingredient (b) is represented in the specified composition in a ratio of about 1:1 and the specified ingredient (a) is present in the means of personal hygiene in the amount of about 0.02 wt.%.

12. A means of personal hygiene to reduce the irritation of the skin containing composition with anti-inflammatory properties, containing (a) an anti-inflammatory agent containing olive leaf extract (Olea Europea) in an amount of about 0.02 wt.% from the specified composition and (b) an anti-inflammatory agent containing a combination of sodium chocolatechocolate, asparate magnesium and asparate potassium, in the amount of about 0.02 wt.% from this composition, and the ingredient (a) and ingredient (b) is represented in the specified composition in a ratio of about 1:1 and the specified anti-inflammatory composition is present in the means of personal hygiene in the amount of about 0.02 wt.%.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to novel pyrimidine derivatives of formula (I) or their pharmaceutically acceptable salts which possess inhibiting activity with respect to focal adhesion kinase (FAK), proteintyrosinekinase ZAP-70, receptor of insulin-like growth factor 1 (IGF-1R), tyrosinekinase activity of anaplastic lymphoma (ALK) and fusion protein NPM-ALK. In formula (I) , R0, R1 and R2 independently represent hydrogen, C1-C8 alkyl, 5- or 6-member heterocycle, containing 1,2 or 3 heteroatoms, selected from N, O and S, C1-C8alkoxy group, C1-C8alkylsulphinyl, C1-C8alkylsulphonyl, C5-C10arylsulphonyl, halogen, carbamoyl, sulphamoyl, etc.; R3 represents C1-C8alkylsulphinyl, C1-C8alkylsulphonyl, C5-C10arylsulphonyl, carbamoyl or sulphamoyl; R4 represents hydrogen or C1-C8alkyl; R5 represents chlorine or bromine; R6 represents hydrogen; R7, R8, R9 and R10 independently represent C1-C8alkyl, C5-C10aryl, possibly substituted by 5- or 6-member heterocycle, containing 1, 2 or 3 heteroatoms, selected from N, O and S, where substituents are selected from C1-C8alkyl, hydroxy, hydroxy-C1-C8alkyl, C1-C8alkoxy C1-C8alkyl, cyano, oxo, C1-C8alkylamino, diC1-C8alkylamino, carbamoyl, C1-C8alkylcaronyl, 5-10-member heterocycle, containing 1, 2 or 3 heteroatoms, selected from N and O, which is probably substituted by C1-C8alkyl; C1-C8alkoxy group, halogen- C1-C8alkoxy group, etc; A represents C. Invention also relates to pharmaceutical composition and to application of compounds of formula (I) for preparation of medication.

EFFECT: novel compounds possess useful biologic activity.

15 cl, 61 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I

in form of a salt, where R1 and R2 each independently denotes phenyl, where one or both R1 and R2 are substituted in one, two or three positions by the following groups: halogen, C1-C8alkyl or C1-C8alkoxy, and R3 is hydroxy, or R1 and R2 each denotes an unsubstituted phenyl, and R is hydrogen, C1-C8alkyl, C1-C8alkoxy or C1-C8alkylthio, or R1 is C3-C8cycloalkyl and R2 is phenyl or a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes oxygen and sulphur, and R3 is hydroxy, or -CR1R2R3 denotes 9-hydroxy- 9H-fluoren-9-yl or 9-hydroxy-9H-xanthen-9-yl, and R4 is C1-C8alkyl substituted in one, two or three positions by a -CO-N(R5)R6 group, where R5 is hydrogen and R6 is a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes nitrogen and oxygen, optionally substituted with phenyl, or R1 and R2 each denotes an unsubstituted phenyl, and R3 is hydroxy and R4 is C1-C8alkyl substituted in one, two or three positions by a -CO-N(R5)R6 group, where R5 is hydrogen and R6 is 5-methyl-3-isoxazolyl or R1 and R2 each denote unsubstituted phenyl, and R3 is hydroxy and R4 is 1-ethyl substituted in one, two or three positions by a -CO-N(R5)R6 group, where R5 is hydrogen, R6 is a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes nitrogen and oxygen, provided that the formula I compound is not (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(pyrazin-2-ylcarbamoylmethy)-1-azoniumbicyclo[2.2.2]octane, (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(isoxazol-3-ylcarbamoylmethyl)-1-azoniumbicyclo [2.2.2]octane bromide or (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(pyrimidin-4-ylcarbamoylmethyl)-1-azoniumbicyclo [2.2.2]octane bromide. The invention also relates to a pharmaceutical composition, to use of compounds in any of claims 1-8, as well as to methods for synthesis of formula I compounds.

EFFECT: obtaining new biologically active compounds which have M3 muscarinic receptor mediated activity.

14 cl, 254 ex, 1 tbl

Composition // 2398587

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicinal agents and concerns a composition for preparing a medicinal agent for local treatment of inflammations, containing at least, one glucocorticoid and N-chlorotaurine or N-chlorotaurine salt. There is also discovered a medicinal agent containing specified composition and application of the composition for preparing a medicated mixture for local treatment of inflammations.

EFFECT: lowered profile of (toxic) by-effects.

13 cl, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, and concerns a method for cutting time of manifestation of anaesthetising/antipyretic composition containing an effective amount of an anaesthetic/antipyretic agent containing acetylsalicylic acid, acetaminophen, caffeine and an alkaline agent, and said method involves addition to the composition of at least one alkaline agent cutting time of manifestation of the anaesthetising/antipyretic composition.

EFFECT: quick manifestation of anaesthetising/antipyretic effect, non-toxicity.

9 cl, 4 ex, 4 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine and is intended for pain-killing, anti-inflammatory and febrifugal action in case of application group NSAID medications with different points of impact. Medications ketorol and nise are used in combination and successively. On the first day after operational intervention perorally introduced is ketorol in dose 10 mg every 4-6 hours. On the second day introduced is nise in dose 100 mg 2 times a day for 5 days. Total course of treatment constitutes 5-7 days.

EFFECT: method allows to increase efficiency of pharmacological disease treatment, ensure possibility to reduce treatment course due to high efficiency of said combined scheme of treatment which combines pain-killing and anti-inflammatory action, reduce number of side effects of applied drugs, alleviate the course of said diseases.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to an antimicrobial, anti-inflammatory and anaesthetic agent. The antimicrobial, anti-inflammatory and anaesthetic agent containing dry extract of Veronica chamaedrys herb, anilocaine and Dimexid in the form of an aqueous mixture purified in the ratio 1:1, at the certain relation of components. A method for preparing the agent involving dissolution of dry extract of Veronica chamaedrys herb in the aqueous mixture of Dimexid purified in the ratio 1:1, in the specific environment; thereafter the solution is cooled to room temperature, added with anilocaine at stirring and filtered.

EFFECT: agent described above exhibits effective complex antimicrobial, anti-inflammatory and anaesthetic action.

2 cl, 6 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to molecular pharmacology and specifically to a peptide which is part of an interleukine-15 (IL-15) sequence which can inhibit biological activity of the said molecule.

EFFECT: obtaining a peptide which inhibits T cell proliferation induced by IL-15, and apoptosis caused by tumour necrosis factor when bonding with the alpha subunit of the (IL-15R) receptor.

8 cl, 4 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel biologically active substances of the class of complex compounds of N-heterylamides of 4-aryl-2,4-dioxobutanoic acids. The invention discloses bis{3-phenyl-1-[2-(5-methyl-1,3,4-thiadiazolyl)]carboxamido-1,3-propanedionato}manganese having anti-inflammatory and analgesic activity and formula: .

EFFECT: high output of compounds with pronounced anti-inflammatory and analgesic activity, as well as low toxicity.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-(2-benzothiazolyl)amide 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenoic acid of formula: , which has antimicrobial and anti-inflammatory activity along with low toxicity.

EFFECT: obtaining a compound which can be used to treat diseases associated with pathogenic microorganisms and inflammation.

1 cl, 2 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of general formula (I), where R1 - C1-C6alkyl, (C1-C6alkyl)C1-C6alkyl, di(C1-C6)C1-C6alkyl or C3-C6dicloalkyl; each R2 independently represents halogen, C1-C6alkyl, halogen-substituted C1-C6alkyl or cyano; R3 - hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkinyl, hydroxyl, hydroxy-substituted C1-C6alkyl, C1-C6alkoxy, C3-C6cycloalkyl, cyano, C(=O)H, phenyl, (C3-C6cycloalkyl)C1-C6alkoxy, (C1-C6alkoxycarbonylamino)C1-C6alkoxy or (C1-C6alkylcarbonylamino)C1-C6alkoxy; R4 represents hydroxyl, C1-C6alkoxy, the group -NH(C=O)R4a, where R4a is halogen-substituted C1-C6alkyl, or the group -NH(CH2)2OR4b, where R4b is benzyl or phenyl ethyl; and m = 1 or 2 in a free form or in the form of pharmaceutically acceptable salt. Besides the invention refers to a pharmaceutical composition of the compounds applied for treatment or prevention of a disease or condition wherein vaniloid receptor activation acts the part or participates.

EFFECT: invention refers to application of the named compounds for preparing a drug to be applied for treatment or prevention of pain or gastrointestinal disturbance.

20 cl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is offered an antioxidant and antihypoxic agent represented by an infusion solution and containing 0.5-10.0 of 6-methyl-2-ethyl-3-hydroxy-pyridine succinate, sodium chloride, sodium hydroxide or hydrochloric acid and water for injections in a certain ratio, g/l. The agent (Mexidol for injections) is used for treatment of acute and chronic disturbed cerebral circulation of ischemic and hemorrhagic nature, acute myocardial infarction, prevention of reperfusion syndrome, unstable angina, acute and chronic pancreatitis. The stabilisation is ensured by prevention of oxidation of a 6-methyl-2-ethyl-3-hydroxy-pyridine succinate molecule.

EFFECT: infusion form is characterised by higher storage stability.

3 ex

FIELD: medicine.

SUBSTANCE: invention relates to method of obtaining medication on the basis of biologically active substance, which includes binding biologically active substance to neutral carrier, as neutral carrier metal or semiconductor nanoparticles are used, and as biologically active substance used is bacteriorodopsin in therapeutically efficient amount, whose molecules are linked to nanoparticle surface with formation of ligand shell.

EFFECT: obtained nanoparticles ensure efficient transportation of bacteriorodopsin into cells and tissues.

10 ex

FIELD: medicine.

SUBSTANCE: invention relates to medical agents and concerns a remedy in the form of an injection precursor product for obtaining liquid injectable composition, containing as agent for prevention and/or treatment of neurodegenerative diseases, nervous disorders or diseases requiring nerves regeneration the effective quantity of (2R)-2-propyloctane acid or salt thereof, and 1-5 equivalents of the basic ion of metal as per 1 equivalent of (2R)-2-propyloctane acid or salt thereof, metal salt selected from phosphoric acid metal salt, carbonic acid metal salt, and sulfurous acid metal salt and may optionally contain metal hydroxide as the source(s) of the basic metal ion.

EFFECT: development of the remedy which is resistant to pH fluctuations and does not grow turbid at solution.

21 cl, 3 dwg, 21 tbl, 22 ex

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical composition, which contains ZD6474 or its pharmaceutically acceptable salt, fragile thinner and second thinner, which is practically insoluble and possesses compression plasticity. Fragile thinner represents calcium hydrophosphate, and second thinner, which is practically insoluble and possesses compression plasticity, represents microcrystalline cellulose.

EFFECT: good bioavailability for active substance.

5 cl, 7 tbl, 5 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: peroral medicinal form with immediate release of derivatives of benzapene-1-acetic acid includes said active substance in amount up to 65% of total weight of medicinal form; 10% wt of alkaline compound or mixture of alkaline compounds; from 0.1 to 10% of one or more surface-active substances, and optionally includes auxiliary materials in amount from 1% to 45% of total medicinal form weight. Invention also relates to methods of obtaining said medicinal form.

EFFECT: invention allows to obtain stable in application medicinal forms with increased biological availability of active substance.

21 cl, 3 dwg, 5 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical composition for peroral introduction, which possesses time of release delay, which includes particles containing medication in pharmaceutical composition core; medium layer, which contains two types of water-soluble components: solubility-reducing agent of salting-out or acid type and changed into insoluble form substance of salting-out or acid type; and external layer for regulating rate of water penetration, which contains water-insoluble substance.

EFFECT: invention ensures possibility of temporary defense against insoluble substance dissolving, ensures quick release of medication after definite delay time with possibility to control delay time.

12 cl, 18 dwg, 3 tbl, 31 ex

FIELD: medicine.

SUBSTANCE: method includes following stages: mixing of water with compound composition, including preparation, modifying rheology, and therapeutically active compound, for obtaining paste; extruding portion of paste for extrudate formation; spheronisation of extrudate portion for formation of spheronised particles, and drying of portion of spheronised particles. Said method includes control of water content, used in compound composition, for obtaining from 80 to 98% of particles, which have diametre from 800 to 1500 mcm.

EFFECT: possibility of application in pharmaceutics.

25 cl, 3 dwg, 3 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: combined chondroprotective pharmaceutical composition is made in the form of gel and contains chondroitin sodium sulphate, glucosamine sulphate sodium chloride, propylene glycol, Carbomer (Carbopol), lavender oil, methyl parahydroxybenzoate (Nipagin, methylparaben), sodium methabisulphite, ethanol and purified water in the relevant ratio of the components.

EFFECT: stimulated mechanisms of cartilage reparation, suppressed activity of enzymes destroying cartilage tissue, anaesthetising and antiinflammatory action within an application area.

1 ex

FIELD: medicine.

SUBSTANCE: present invention concerns medical products, particularly a liquid pharmaceutical composition containing ionite bound Pradofloxacine, and filled ionite is dispersed in a carrier medium containing water and one or more structurally viscous gelling agents, and the elastic ratio of the composition makes 5 to 50 Pa, and also to application thereof for making a medical product.

EFFECT: compositions shows improved physical stability and provide available intake of the preparation by animals.

5 cl, 1 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: present group of inventions concerns medicine, more specifically coated implants and devices. There is offered ceramic composition-precursor for making high-strength bio-elements used as an absorbable or partially absorbable biomaterial where the composition contains at least one silicate with Ca as a base cation with the absorption rate less or equal to the bone growth rate, and this at least one silicate acts as a base binding phase in a biomaterial, and this at least one silicate Ca is present in amount 50 wt % or more, and all other components if any are presented by additives, such as an inert phase, and/or additives which make a biomaterial to be radiopaque. There is offered hardened ceramic material which is based on the ceramic composition-precursor and is in the hydrated form. There is offered a medical implant, application of the medical implant, and also a device or a substrate coated with the uncured ceramic composition-precursor and/or hardened ceramic material.

EFFECT: invention provides a biomaterial having initial and constant durability which is dissolved in due time and reacts with an organism to generate a new tissue.

29 cl, 1 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: rehabilitation of children with remitted chronic rhinosinusitis is ensured by the administration of Sinupret as a cytoprotector. The preparation is introduced by 25 drops 3 times a day, daily for 24-30 days. Rehabilitation is conditioned by ensured competence of nasal mucosa cells due to newly ascertained reparative ability of Sinupret, with local destructive processes of pavement and columnar epithelium cells and neutrophils be decreased.

EFFECT: higher rehabilitation effectiveness.

5 tbl, 2 ex

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