EA019154B1 - Hexapeptides and compositions thereof - Google Patents

Abstract

The present invention relates to peptides of the formula Tyr-X-Gly-Phe-X-Xwherein if Xis Gly or L-Ala, Xis independently Leu, Met, Ile, or Val; and Xis independently Asp or Glu; or if Xis D-Ala and Xis Asp, Xis independently Leu, Met, Ile, or Val; or if Xis D-Ala and Xis Glu, Xis independently Met, Ile, or Val; and compositions thereof.

Description

Field of Invention

The invention relates to new hexapeptides and compositions based on them. In particular, it relates to skin care compositions and dermatological compositions containing these hexapeptides.

BACKGROUND OF THE INVENTION

There are no published or published data pertaining to the new hexapeptides of the general formula Tut-X ₁ -61y-Rye-X ₂ -X ₃ , where if X! - this is C1u or L-A1a, then X ₂ is independently Le, Me1. Not or Wa1; and X ₃ is independently Acre or 61i; or, if X ₁ is E-L1a and X ₃ is Acre, then X ₂ is independently Le, Me1, 11e or Wa1; either their derivatives or salts; as well as data related to the use of these peptides as ingredients in skin care and dermatological compositions.

In a way that was not obvious from the prior art, we found that when applied externally to the skin, these peptides help improve blood microcirculation in the vessels of the skin, especially aging skin.

The purpose of the invention is to offer these new peptides and compositions based on them for pharmacology and dermatology.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a peptide characterized by the general formula (I) Tut-X ₁ -61y-Rye-X ₂ -X ₃ where, if X ₁ is C1u or L-A1a, then X ₂ is independently Lei, Me1, 11e or Wa1; and X ₃ is independently Acre or 61i; or, if X ₁ is E-L1a and X ₃ is Acre, then X ₂ is independently Le, Me1, 11e or Wa1; or, if X ₁ is O-A1a and X ₃ is 61i, then X ₂ is independently Me1, 11e or Wa1.

As used herein, the term “peptide” means a sequence of six amino acid residues, wherein the claimed amino acids may be in b- or Ό-form. In preferred embodiments of the invention, the amino acids are in L form. In some embodiments of the present invention, alanine may be in either b or b form.

In preferred embodiments of a practical embodiment of the present invention, a peptide having the general formula (I) is selected from the group consisting of

- 1 019154

Further, the present invention provides a pharmaceutical composition, characterized in that it contains a peptide having an amino acid sequence selected from the group consisting of

8Eph GO ΝΟ: 1, Zef GO ΝΟ: 2, 8Eph GO N0: 3, 8Eph GO N0: 4, 8Eph GO N0: 5,

ZEP GO N0: 6, ZEP GO N0: 7, ZEP GO N0: 8, ZEP GO N0: 9, ZEP GO N0: 10,

ZEP GO N0: 11, ZEP GO N0: 12, ZEP GO ΝΟ: 13, ZEP GO N0: 14, ZEP GO N0:

15, Zef GO N0: 16, Zef GO ΝΟ: 17, Zef GO ΝΟ: 18, Zef GO N0: 19, Zef GO

N0: 20, Zef GO N0: 21, Zef GO N0: 22, Zef GO N0: 23;

and a pharmaceutically acceptable carrier.

Further, the present invention provides a skin care composition, characterized in that it comprises a peptide having an amino acid sequence selected from the group consisting of

ZEP GO N0: 1, ZEP GO N0: 2, ZEP GO N0: 3, ZEP GO N0: 4, ZEP GO N0: 5,

ZEF GO N:: 6, ZEF GO ΝΟ: 7, ZEF GO ΝΟ: 8, ZEF GO ΝΟ: 9, ZEF GO ΝΟ: 10,

ZEP GO ΝΟ: 11, ZEP GO N0: 12, ZEP GO N0: 13, ZEP ΙΟ ΝΟ: 14, ZEP GO N0:

15, GEF GO N0: 16, GEF GO N0: 17, GEF GO N0: 18, GEF GO N0: 19, GEF GO

N0: 20, Zef GO N0: 21, Zef GO ΝΟ: 22, Zef GO N0: 23;

and a dermatologically acceptable carrier.

Further, the present invention provides a dermatological composition, characterized in that it contains a peptide having an amino acid sequence selected from the group consisting of

ZEP GO ΝΟ: 1, ZEP GO ΝΟ: 2, ZEP GO ΝΟ: 3, ZEP GO ΝΟ: 4, ZEP GO N0: 5,

ZEP GO N0: 6, ZEP GO N0: 7, ZEP GO N0: 8, ZEP GO ΝΟ: 9, ZEP GO N0: 10,

ZEP GO N0: 11, ZEP GO N0: 12, ZEP GO N0: 13, ZEP GO ΝΟ: 14, ZEP GO ΝΟ:

15, Zef GO N0: 16, Zef GO ΝΟ: 17, Zef GO N0: 18, Zef GO ΝΟ: 19, Zef GO

ΝΟ: 20, Zef ΙΟ ΝΟ: 21, Zef GO N0: 22, Zef GO ΝΦ: 23;

and a dermatologically acceptable carrier.

As used herein, the term skin care composition means a composition for external application to human skin to improve the appearance and condition of the skin. In this regard, the term skin / skin covers all skin or any area of the skin, including hair, nails, etc.

As used herein, the term “dermatological composition” means a pharmaceutical composition designed for skin use, for example, for application to a skin site affected by a skin disease or inflammation. Examples of such diseases and conditions include decreased skin elasticity, reduced skin density, loss of natural skin moisture, dry skin, itchy skin, boils, acne, wrinkles, lentiginosis, age-related (senile) spots, skin melanosis, hyperpigmentation, hyperkeratotic formations on the skin, skin atrophy, senile purpura, psoriasis, eczema, inflammatory dermatosis, spider veins (arachnid veins), keratoses, as well as brittle hair and nails. Other skin diseases that can be treated using the composition of the present invention include those described by Friedberg et al. (Egheebbegde e! A1.), In Dermatology in Medicine Fitzpatrick, 6th ed., 2003 (ΡίΙζραίΓίοΚ'δ Ogta! Oododa ίη Seiega1 Mebkte (6! 1ι Εάίίίοη, 2003)), Kerdel et al. (Кег6е1, е! А1.) Treatment of dermatological diseases (Oegta! O1osche Tyegareiysk (2005)), as well as in Nagbtai e! A1., Soobtai & Sytai'k: Pharmacological basis of therapy, 10th ed., 2001. (Thye P11agtaeo1aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa!

The peptide content in the present invention ranges from 0.00001 to 10%, preferably from 0.0001 to 0.1%, relative to the weight of the entire composition.

As used herein, the term “dermatologically acceptable carrier” means one or more liquid, semi-solid or solid solvents suitable for use on any part of the human skin and compatible with peptides of general formula (I), as well as other active active ingredients and additional ingredients of the present invention. Examples of such carriers include, but are not limited to, distilled or deionized water, propylene glycol, glycerol, and oil.

The compositions of the present invention can be used to control the condition of the skin, visible or perceptible violations of the integrity of the skin (especially the surface of the skin; such violations are usually undesirable). Such disorders can be caused or result from exposure to internal and / or external factors, they include signs of skin aging described in

- 2 019154 this document. The term skin regulation includes prophylactic regulation and / or therapeutic regulation of skin conditions, including visible and / or perceptible violations of the integrity of the skin. In this document, prophylactic regulation of the skin condition means slowing down, minimizing and / or preventing the appearance of visible and / or perceptible violations of the integrity of the skin. In this document, therapeutic regulation of the skin condition means improving the skin condition, for example, reducing, minimizing and / or smoothing the integrity of the skin. The regulation of the condition of the skin includes improving both the appearance and sensation of the skin. In addition, the compositions of the present invention are particularly useful for the treatment of acne, as well as other skin diseases and inflammations.

The compositions of the present invention are particularly suitable for treating signs of aging of the skin, especially on visible or perceptible disturbances in the integrity of the skin associated with aging. Exposure to signs of skin aging includes a prophylactic and / or therapeutic effect on one or more of these signs (likewise, exposure to a particular sign of skin aging, such as wrinkles, wrinkles, pores, includes prophylactic and / or therapeutic impact on this symptom). As used herein, a prophylactic effect on such signs includes slowing, minimizing and / or preventing the appearance of signs of skin aging. As used herein, therapeutic effects on such signs include improving the condition of the skin, for example, weakening, minimizing and / or smoothing out signs of skin aging.

Signs of skin aging include, but are not limited to, all external visible and palpable tactile manifestations, as well as other macro- and micro-effects of skin aging. Such signs may be caused or result from exposure to internal or external factors, such as age-related (chronological) aging and / or environmental influences. These signs may be the result (but not limited to only) of such processes as the development of structural disorders, such as wrinkles, both fine and small superficial and large deep wrinkles, skin lines and folds, cracks, irregularities, bumps, large pores (for example associated with accessory structures such as ducts of the sweat glands, sebaceous glands and hair follicles), roughness, lamination and / or other forms of manifestation of skin irregularities, loss of skin elasticity (loss and / or inactivation of skin elastin), sagging I (including swelling in the eyes and double chin), loss of skin hardness, loss of density, loss of elasticity during deformation, discoloration (including circles under the eyes), spots, yellowish color, hyperpigmented areas of the skin, such as , age (senile) spots and lentigo, keratosis, atypical differentiation, hyperkeratosis, elastosis, collagen rupture, as well as other histological changes in the stratum corneum, dermis, epidermis and skin vascular system (for example, telangiectasia or vascular stars hibernation), and underlying tissues, especially those located close to the skin.

The compositions of the present invention may contain additional ingredients. Such additional ingredients are usually used individually in a volume of from 0.0005 to 10.0%, preferably from 0.0005 to about 1.0%, relative to the weight of the entire composition.

Examples of suitable additional ingredients are, but are not limited to, depigmentation promoting substances; humidifiers; bactericidal (e.g. antibacterial) substances; anti-acne substances; substances that slow down the aging process; anti-wrinkle substances, antiseptic agents; local anesthetics; substances that promote wound healing; deodorants and antiperspirants; means for moisturizing and softening the skin; components that contribute to tanning; bleaching agents; antifungal agents; means for depilation; painkillers for external use; substances that relieve irritation; means to prevent diaper rash; makeup products; vitamins and nutrients such as thiamine, riboflavin, niacin, pantothenates, pyridoxine, folic acid, cobalamin, biotin, choline, inositol, ascorbic acid, lipoic acid, carnitine, etc .; amino acids and their derivatives, such as alanine, arginine, asparagine, aspartic acid, carnitine, citrulline, cysteine, dimethylglycine, gamma-aminobutyric acid, glutamic acid, glutamine, glutathione, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine; mineral elements such as boron, calcium, chromium, cobalt, copper, fluorine, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium, zinc; plant extracts; retinoids; bioflavonoids; antioxidants; substances with skin conditioner properties; clarifiers for hair; chelating agents; cell renewal enhancers; dyes; as well as a mixture of the above components.

Examples of suitable humectants include, but are not limited to, water-soluble liquid polyhydric alcohols (polyols) from the group consisting of glycerol, propylene glycol, hexylene glycol, butylene glycol, pentylene glycol, dipropylene glycol, and mixtures thereof.

Suitable amino acids include amino acids obtained by hydrolysis of various proteins, as well as their salts, esters and acyl derivatives. Examples of such amino acids may

- 3 019154 are amphoteric amino acids, such as alkylamidoalkylamines, for example stearyl acetyl glutamate, capryloyl silk amino acids, capryloyl collagen amino acids; capryloyl keratin amino acids; capryloyl green pea amino acids; cocodimonium hydroxypropyl silk amino acids; corn gluten amino acids; cysteine; glutamic acid; glycine; amino acids of hair keratin; hair amino acids such as aspartic acid, threonine, serine, glutamic acid, glycine, alanine, half-cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, cysteic acid, lysine, histidine, arginine, cysteine, tryptophan, citrulline; lysine; silk amino acids, wheat amino acids; as well as a mixture of the above substances.

Examples of suitable proteins are (but are not limited to) collagen, deoxyribonuclease, iodinated corn grain protein; keratin; milk protein; protease; Whey Protein; silk; sweet almond proteins; wheat germ proteins; wheat proteins; wheat proteins; alpha and beta helix of keratin proteins; hair proteins such as intermediate filament proteins, high sulfur proteins, ultra high sulfur proteins, intermediate filament proteins, tyrosine high proteins, glycine and tyrosine high proteins, trichogialine, arginine-rich peptides such as oligoarginines ( Arg) ₈ , or a mixture of the above substances.

Examples of suitable antiperspirants and deodorants include, but are not limited to, aluminum hydrochlorides, aluminum and zirconium hydrochlorides, as well as mixtures of the above.

Examples of suitable irritant-removing agents include, but are not limited to, camphor, menthol, methyl salicylate, peppermint and clove oil, ichthammol, and mixtures of the above.

Examples of suitable anti-aging processes include, but are not limited to, retinoids; vitamins such as vitamin C, vitamin B and their derivatives; antioxidants, including acids, such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid, alpha-hydroxyisocaproic acid, atrolactic acid, alpha-hydroxyisovaleuronic acid, these , glucoheptonic acid, 1,4lactone of glucoheptonic acid, gluconic acid, gluconolactone, glucuronic acid, glucuronolactone, glycolic acid, isopropylpyruvate, m ethyl pyruvate, mucic acid, pyruvic acid, sugar, acid, 1,4-lactone sugar, tartaric acid and tartronic acid; succinic acid or its salts; acids such as beta-hydroxybutyric acid, beta-phenyl lactic acid, beta-phenylpyruvic acid; plant extracts such as extract of green tea, soy, milk thistle (milk thistle), seaweed, aloe, angelica, bitter orange, coffee, smoked fruit (gold thread), grapefruit, fungus mushroom, honeysuckle, cuckoo tears (Job's tears), lithosperm (passerine), mulberry (mulberry), peony, pueraria, rice, safflower, or a mixture of the above extracts.

Examples of suitable depigmentation agents include, but are not limited to, hydroquinone and its derivatives; vitamins such as niacin, vitamin C and its derivatives; extracts, such as chamomile and green tea extract, as well as mixtures thereof.

Examples of suitable skin whitening components include, but are not limited to, hydroquinone, catechol and its derivatives, ascorbic acid and its derivatives, as well as a mixture of the above substances.

The compositions of the present invention are prepared using well-known procedures. Such procedures include (but are not limited to) mixing the peptides of the present invention with other ingredients of the composition by the traditional method. Guidance on the preparation of cosmetic and dermatological compositions of this invention can be found in the following reference: Remington: The Science and Practice of Pharmaceuticals, 20th ed. (Ket1id1oy: You do not have all the apostles rtasbse ο Ма riattasu 201st eb. Mask RIBNyid, EVYuP RA, 2000 Ι8ΒΝ 0-912734-04-3), as well as in the Encyclopedia of Pharmaceutical Technology (Exodus 1. . & 1. With Wow1ai, Magse1 Ekeket, 1is., Уον Watk, 1988 Ι8ΒΝ 0-8247-2800-9 or in a more recent version). As is well known to qualified persons, characteristic additives to dermatological compositions include (but are not limited to) ointment bases, solvents, buffering agents, pH-maintaining substances, preservatives, moisturizers (moisture-retaining substances), chelating agents, antioxidants, stabilizers, emulsifiers , suspending components, gelling components, flavoring agents, as well as skin protection products.

The compositions of the present invention can be presented in various forms. These forms include, but are not limited to, lotions, gels, creams, sprays and solutions.

The compositions of the present invention can be used to regenerate damaged hair and stimulate hair growth. In addition, the compositions of the present invention are particularly useful for improving the condition and appearance of nails, enhancing the growth and regeneration of nails, for giving nails strength and flexibility, and also for eliminating problems associated with nails, such as changing shape and

- 4 019154 texture of the nail plate, thickening of the nails, fragility and brittleness of the nails.

The compositions of the present invention are particularly useful for influencing local body fat, including cellulite. The term local body fat refers to areas of excess sebum, such as cellulite, as well as excess adipose tissue. The term cellulite means deposits of adipose tissue, which usually do not respond to diet and exercise. Cellulite is not the only cosmetic disease found in women. Striae (stretch marks) is another cosmetic defect that occurs not only in women, but also in men.

The invention provides a skin care method comprising the step of applying an effective amount of a composition of the present invention to skin, hair or nails. According to the method described in the present invention, an effective amount of the composition is applied to the skin, after which it is desirable to leave it on the skin for at least 15 minutes, more preferably for about 30 minutes, and even more preferably for about 1 hour, most preferably several hours, for example up to 12 hours. This method can be repeated from 1 to 5, preferably 1-3 times a day. Typically, an effective amount of the composition is from 1 to about 100 g, preferably from 1 to about 20 g.

The invention provides a method of dermatological care / treatment, comprising the step of applying an effective amount of a composition of the invention to the skin. According to the method described in the invention, an effective amount of the composition is applied to the skin, after which it is desirable to leave it on the skin for at least 15 minutes, more preferably for about 30 minutes, and even more preferably for about 1 hour, most preferably for several hours for example, up to 12 hours. This method can be repeated from 1 to 5, preferably 1-3 times a day. Typically, an effective amount of the composition is from 1 to about 100 g, preferably from 1 to about 20 g.

The compositions of the present invention are usually designed so that the pH of the composition is from 4.5 to 9.5, more preferably from about 5 to 8.5.

Peptides can be obtained by solid phase peptide synthesis (TPS). In a preferred embodiment of the present invention, according to the TPS method, protected amino acids in organic solvents are added to the resin bound peptide chain, which results in the preparation of the target peptide with a specific sequence in a fully protected bound resin form. After that, the finished peptide can be isolated by deprotection and cleavage from the polymer carrier. Such a synthesis can be carried out using both automated and automated methods.

The following examples are provided to demonstrate the invention. The examples are illustrative only, they should in no way limit the scope of the invention.

Example 1

This example demonstrates the preparation of the peptides of the present invention and their anti-inflammatory activity.

Peptides with the amino acid sequences of 8EC C N0: 1 to 23 were obtained by the method of solid-phase peptide synthesis (TPS), using the classical C. C. Vu1.Sieesh procedure. 271, 29537-44, 1996), using an automatic peptide synthesizer (Arrieb VuvuCheshv 430A Reribe ZupShebheg) according to the instructions given in the instruction manual provided by the supplier. Peptides were isolated in the form of acetates with an average purity> 90%.

The anti-inflammatory activity of peptides 8EC C N0: 1-23 was tested ίη νίΐτο. In a human keratinocyte culture, the effectiveness of peptides was shown to suppress the production of pro-inflammatory cytokine interleukin-1a by cells in response to stimulation by interleukin-1 beta. Stimulation of keratinocytes of 0.5 μg / L interleukin-β for 48 h leads to a 55-fold increase in the release of pro-inflammatory cytokine interleukin-1a by cells (1,400 μg / L compared to 0.024 μg / L in the control), which characterizes the developing inflammatory process. An additional introduction of peptides at a concentration of 7 mg / L into the incubation medium led to a significant decrease in the stimulated production of interleukin-1a by cells to levels not exceeding 0.300 μg / L for all studied peptides 8EC EC N0: 1-23. Thus, the peptides of the present invention have pronounced anti-inflammatory properties, which makes them useful in pharmaceutical and dermatological compositions.

Example 2

This example demonstrates a composition in the form of a gel for skin care.

- 5 019154

Ingredients Content A peptide selected from the group of the following 1 mg sequences: 8Е () Ιϋ ΝΟ: from 1 to 23 Phosphate buffer Amount sufficient for maintain pH 5.5 Ethyl cellulose 60 mg Deionized water Up to 10.0 ml

Preparation of the gel: the peptide is mixed with the above ingredients in the traditional way to obtain a gel for skin care.

Method for skin care using a gel: Apply 1 ml of the aforementioned gel to the skin of the face, preferably left on the skin for at least 15 minutes.

Example 3

This example demonstrates a pharmaceutical dermatological composition in gel form.

Ingredients Content A peptide selected from the group of the following 1 mg sequences: 5Eph Yu N0: 1 to 23 Phosphate buffer Amount sufficient for maintain pH 5.5 Ethyl cellulose 60 mg Deionized water Up to 10.0 ml

Preparation of the gel: the peptide is mixed with the above ingredients by the traditional method to obtain a dermatological composition in the form of a gel.

Method of skin treatment using gel: Apply 1 ml of the aforementioned gel to the skin of the face, preferably left on the skin for at least 15 minutes.

Example 4

This example demonstrates the effectiveness of an external composition containing the peptide 8Ef ΙΌ N0: 3 as a skin care product.

A composition containing 0.02% hexapeptide with an amino acid sequence of 8Ef ΙΌ N0: 3 was applied to the area under the eyes of volunteers with characteristic dark circles (n = 19, women, average age 45.6 ± 10.9 years) twice a day, for four weeks. The effectiveness of skin moisturizing was evaluated using the device Sogpsots1g SM825. The skin hydration level after four weeks of use significantly increased by 22% (p <0.01). Visual assessment of photos of volunteers made using the UyoGaes Oshek device. showed a decrease in dark circles under the eyes of 58% of the volunteers. Thus, the external composition containing the peptide of the present invention is effective in improving skin hydration and improving the appearance of the skin.

Example 5

This example demonstrates the effectiveness of an external dermatological composition containing the peptide 8Ef ΙΌ N0: 3, as a means to reduce the effects of sunburn.

A composition containing 0.02% hexapeptide with an amino acid sequence of 8Ef ΙΌ N0: 3, or a placebo, was applied to the reddened and swollen area of the skin of the back, subjected to sunburn, to volunteers (n = 6, men, average age 41 ± 12 years). Efficiency was assessed by the time required to relieve burn symptoms. The average time to relieve burn symptoms in the group using the composition containing the peptide was 2.1 times faster than in the placebo group. Thus, a dermatological composition comprising a peptide of the present invention is effective in reducing the effects of sunburn.

- 6 019154

LIST OF SEQUENCES OF AMINO ACIDS <110> υΝΙΤΕ.η TESNZH) ЬОС1Е8 и АС <120> HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130> 772/10 <150> PCT / EP 2008/055011 <ON160SERNOPSER1011EREPLES1151ESERNOZER1151ESLET’s 04.151ESLET PER_1601ESLET_1601SEL'S PER_1601SEL'S1011EPER_1601SER1 GO N05: 23 <210> 8EO GO ΝΟ: 1 <211> LENGTH; 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 1

Tug C1u C1u Rye Ley Azr

5 <110> ΓΓΝΙΤΕϋ TESNIOEOS1E8 and IT AC <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NUMBER: 8Е0 ГО 0808 ГО > 8Εζ * ΙΌΝΟ: 2 <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 2

Tug A1a C1u Rye Ley Azr

5 <1 s> υΝίΤΕϋ τΕΟΗΝουοοίΕδ it as <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEE SEQUENCE NO. N08: 23

- 7 019154 <210> 8ΕφΠ) ΝΟ: 3 <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 3

Tug O-A1a O1u Rye Ley Avr

5 <110> ΓΓΝΙΤΕΠ TESKNO01E8 IT AC <120> HEXAPEPTIDES AND COMPOSITIONS THEREOF <13 0> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NUMBER 5EO GO N05: 23 210> 8E <2 ΙΟΝΟ: 4 <211> LENGTH: 6 <212> TYPE: PKT <213> ORGANISM: Artificial SEQUENCE <220> 8ΙΜΙΤΑΚ .: Tug C1u C1u Pbie Lye <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 4

Tug C1u C1u Rye Not Azr

5 <110> ΗΝΙΤΕΟ ΤΕΟΗΝΟίΟΟΙΕδ it AC <120> HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130 772/10 <150> PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 5ES GO N05: 23 <210> 5Er GO ΝΟ: 5 <211> LENGTH: 6 <212> TYPE: RK.T <213> ORGANISM: Artificial SEQUENCE <220> 51M1DAK: Tug O1u C1u Rye Lei <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE

- 8 019154

Tug A1a O1u Rye Ne Azr

5 <110> υΝΙΤΕΟ CLOSE AXIS with IT JSC <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NUMBER ZEZ GO N08: 23 > 8EC GO ΝΟ: 6 <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <220> 81MGOAK: Tug O1u O1u Rye Ley <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE

Tug P-A1a O1u Rye Ne Azr

5 <110> ϋΝΙΤΕΏ TESNIOOOOO1E8 IT Co. <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NO. 8EO GO N08: 23 <210 > 8ΕΟΙϋΝΟ: 7 <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <220> 81MGOAK: Tug O1u O1u Rye Ley <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 7

Tug O1u O1u Rye MeG Azr

5 <110> ϋΝΙΤΕϋ ΤΕΟΗΝΟΕΟΟΙΕδ IT AO <120> HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130> 772/10

- 9 019154 <150> PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 8Ep GO N08: 23 <210> 8EC1O N0: 8 <211> LENGTH: 6 <212> TYPE: Г'КТ < 213> ORGANISM: Artificial SEQUENCE <220> 81M1EAK: Tug O1u O1u Rie Uie <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 8

Tug A1a 61u Pb Μ βΐ Azr

I 5 <110> ϋΝΙΤΕϋ CLOSE CT AO <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NO. 8EC GO N08: 23 210> 8ETSGOIO: 9 <211> LENGTH: 6 <212> TYPE: PET <213> ORGANISM: Artificial SEQUENCE <220> 81M1LV: Tug SLU <31u РЬЬЬЕ <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE 9

Tug E-A1a O1u Rye Me1 Azr

5 <110> υΝΙΤΕΟ TESNJ) AFTER8 it JSC <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NO. 8EC GO N08: 23 <210> 8EO ΙΟΝΟ: 10 <211> LENGTH; 6 <212> TYPE: RKT

- 10 019154 <213> ORGANISM: Artificial SEQUENCE <220> 8GMP.AK: Tug C1u C1u Pbie Bie <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 10

Tug O1u O1u Rye Ua1 Azr

5 <110> υΝΙΤΕϋ TESNETSOOOO1E8 it JSC <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NO. 8EC 210 N08: > 8EO GO ΝΟ: AND <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <220> PUNAK: Tug 61u O1u Rye Ley <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE

Here A1a O1y Rye Ua1 Azr

5 <1 y> iggeO ΤΕΟΗΝοωοΐΕδ it as <120 HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160 SEQUENCE NO. 8EC GO N08: 23 <210> 8ЕО Ю ΝΟ: 12 <211> LENGTH: 6 <212> TYPE: PKT <213> ORGANISM: Artificial SEQUENCE <220> 81MP.AK: Tug 61u 61u Rye Uye <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 12

Tug O-A1a C1u Rye Ua1 Azr

5

- 11 019154 <110> ϋΝΙΤΕϋ TESNPOOOOO1E8 υΤ JSC <120> HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130> 772/10 <150> PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 23: 08E <210> δΕΟΙΏΝΟ: 13 <211> LENGTH: 6 <212> TYPE: PET <213> ORGANISM: Artificial SEQUENCE <220> 81М1БАЕ: Tug О1у О1у РЬеи <223> ADDITIONAL INFORMATION: synthetic <400 SEQUENCE:

Tug С1у О1у РЬе Лей О1и

5 <110> CMGGEL ΤΕΟΗΝΟΪ.ΟΟΙΕδ um AO <120 HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130 772/10 <150 PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 8EO GO N03: 23 <210> 8EC GO N0: 14 <211> LENGTH: 6 <212> TYPE: PET <213> ORGANISM: Artificial SEQUENCE <220> 81M1AE: Tug O1u O1u Pie Lei <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE

Tug A1a O1u Rye Ley O1i

5 <110> υΝΙΤΕϋ TESNI0Ь001E5 it JSC <120> HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130> 772/10 <150> PCT / EP 2008/055011 <151> 04.24.2008

- 12 019154 <160> SEQUENCE NUMBER 8Ef Yu N08: 23 <210> 8Е0 ГО ΝΟ: 15 <211> LENGTH: 6 <212> TYPE: РКТ <213> ORGANISM: Artificial SEQUENCE <220> 81М1БАК: Туг О1е ОЬу О1уЬ1у1 <223> ADDITIONAL INFORMATION: synthetic <400 SEQUENCE: 15

Tug O1y SPu Rye Pe S1i

5 <110> ΗΝΙΤΕϋ ΤΕΟΗΝΟΣΟΟΙΕδ иТJSC <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 8EO GO N08: 23 <210 > 8ΕΟΙΒΝΟ: 16 <211> LENGTH: 6 <212> TYPE: RK.T <213> ORGANISM: Artificial SEQUENCE <220> 81M1AK: Tug <31u 61y Rye Uye <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 16

Tug A1a SIu Rye Pe O1i

5 <110> υΝΙΤΕΟ TESNIOUSSKT AS <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NUMBER 8EC 210 N08: 8EOGOMO: 17 <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <220> 81MSHAK: Tug С1у 61у Рее Рее

- 13 019154 <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 17

Tug E-A1a O1u Rye Ne O1i

5 <110> ϋΝΙΤΕΟ ΤΕΟΗΝΟΓΟΟΙΕδ IT Co. <120> HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <130> 772/10 <150> PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NO. 5EC GO N05: 23 <210 > 8EC ΙΠ ΝΟ: 18 <211> LENGTH: 6 <212> TYPE: PKT <213> ORGANISM: Artificial SEQUENCE <220> 51M1AK: Tug С1у О1у РЬеи <223> ADDITIONAL INFORMATION: synthetic <400> AFTER SEQUENCE 18

Tug O1u O1u Rye Me! C1 and

5 <110> υΝΙΤΕϋ TESNIOOOOO £ E5 ϋΤ AO <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NUMBER 23 ZET GO N05: <210> 5ΕφΙϋΝΟ: 19 <211> LENGTH: 6 <212> TYPE: PET <213> ORGANISM: Artificial SEQUENCE <220> ZEUNAK: Tug O1u O1u Rye Lye <223> ADDITIONAL INFORMATION: synthetic <400 SEQUENCE 19

Tug A1a O1u Rye Me! <31and

5

- 14 019154 <110> υΝΙΤΕϋ TESN £ LUOS | E8 BT AO <120> HEXAPEPTIDES AND COMPOSITIONS ON THEIR BASIS <13 0> 772/10 <150> PCT / EP 2008/055011 <151> 04/24/2008 <160> SEQUENCE NUMBER 5ЕО ГО N08: 23 <210> -8Е0 ГО ΝΟ: 20 <211> LENGTH: 6 <212> TYPE: PKT <213> ORGANISM: Artificial SEQUENCE <220> 81MSHAK: Tug O1u С1у Рее Бе <223> ADDITIONAL INFORMATION: <400> SEQUENCE: 20

Tug P-A1a O1y Rye Me1O1i

5 <110> Τ'ΝΙ ΓΕϋ ΤΕΟΗΝΟΙΌΟΙΕδ BT AO <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 8Е0 GO N08: 23 <210> 8Ef GO N0: 21 <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <220> 8ΙΜΓΤΑΚ: Tug O1u С1у Рее бе <223> ADDITIONAL INFORMATION: synthetic <400 SEQUENCE 21

Tug O1u O1u Pbu Va1 C1i

5 <110> ϋΝΙΤΕϋ ΤΕΟΗΝΟΕΟΟΙΕδ BT AO <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130> 772/10 <150> PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 8Е0 GO N08: 23

- 15 019154 <210> 8ΕφΠ) ΝΟ: 22 <211> LENGTH: 6 <212> TYPE: PKT <213> ORGANISM: Artificial SEQUENCE <220> 81M1 TANK: Tug С1у О1у РЬЬЬе <223> ADDITIONAL INFORMATION INFORMATION: : 22

Tug A1aO1y Rye Ua1 01i

5 <110> υΝΙΤΕϋ TESNIOOOEZ IT JSC <120> HEXAPEPTIDES AND COMPOSITIONS BASED ON THEM <130 772/10 <150 PCT / EP 2008/055011 <151> 04.24.2008 <160> SEQUENCE NUMBER 8ef GO N08: 23 <210> GO N0: 23 <211> LENGTH: 6 <212> TYPE: RKT <213> ORGANISM: Artificial SEQUENCE <220 81M1 TANK: Tug O1u 01u Rye Yeey <223> ADDITIONAL INFORMATION: synthetic <400> SEQUENCE: 23

Tug 0-A1a O1y Rye Ua1 01i

Claims (4)

CLAIM 1. A peptide characterized by the general formula (Ι) Tug-I-A1a-O1y-Pb-X ₂ -X ₃ where, if X ₃ is Acre, then X ₂ is independently Le, MeG 11e or Wa1; or, if X ₃ is 01i, then X ₂ is independently MeG 11e or Va1. 2. The peptide according to claim 1, selected from the group consisting of Tug-I-A1a-01u-Rye-Eey-Acre (8EO ΙΌ N0: 3) 3. A pharmaceutical composition comprising a peptide having an amino acid sequence selected from the group consisting of: 8E0 ΙΌ N0: 3, 8E0 ΙΌ N0: 6, 8E0 ΙΌ N0: 9, 8E0 ΙΌ N0: 12, 8E0 ΙΌ N0: 17, 8E0 ΙΌ N0: 20, 8Е0 ΙΌ N0: 23; and a pharmaceutically acceptable carrier. 4. A skin care composition comprising a peptide having an amino acid sequence selected from the group consisting of: 8E0 ΙΌ N0: 3, 8E0 ΙΌ N0: 6, 8E0 ΙΌ N0: 9, 8E0 ΙΌ N0: 12, 8E0 ΙΌ N0: 17, 8Е0 ΙΌ N0: 20, 8Е0 ΙΌ N0: 23; and a dermatologically acceptable carrier. 5. A dermatological composition comprising a peptide having an amino acid sequence selected from the group consisting of 8E0 ΙΌ N0: 3, 8E0 ΙΌ N0: 6, 8E0 ΙΌ N0: 9, 8E0 ΙΌ N0: 12, 8E0 ΙΌ N0: 17, 8E0 ΙΌ N0: 20, 8E0 ΙΌ N0: 23; and a dermatologically acceptable carrier. 4 ^^ Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky per., 2