(19)
(11)EP 2 306 999 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
07.09.2016 Bulletin 2016/36

(21)Application number: 09761818.5

(22)Date of filing:  28.07.2009
(51)International Patent Classification (IPC): 
A61K 31/194(2006.01)
A61K 31/23(2006.01)
A61K 45/06(2006.01)
A61K 47/12(2006.01)
A61K 9/00(2006.01)
A61K 31/20(2006.01)
A61K 31/722(2006.01)
A61P 7/00(2006.01)
A61K 47/36(2006.01)
(86)International application number:
PCT/EP2009/059749
(87)International publication number:
WO 2009/150257 (17.12.2009 Gazette  2009/51)

(54)

Compositions for treating rosacea comprising chitosan and a dicarboxylic acid amide

Zusammensetzungen enthaltend Chitosan und Dicarbonamid zur Behandlung von Rosacea

Compositions pour traiter la rosacée comprenants du chitosane et un amide dicarboxylique


(84)Designated Contracting States:
AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR
Designated Extension States:
AL BA RS

(30)Priority: 05.08.2008 EP 08161799

(43)Date of publication of application:
13.04.2011 Bulletin 2011/15

(73)Proprietor: Polichem SA
1526 Luxembourg (LU)

(72)Inventors:
  • MAILLAND, Federico
    CH-6900 Lugano (CH)
  • MURA, Emanuela
    I-22100 Como (IT)

(74)Representative: Pistolesi, Roberto et al
Dragotti & Associati Srl Via Nino Bixio, 7
20129 Milano
20129 Milano (IT)


(56)References cited: : 
WO-A-01/74165
WO-A-2004/082628
WO-A-2007/084998
WO-A-2007/149868
US-A1- 2004 156 873
WO-A-2004/068970
WO-A-2006/010590
WO-A-2007/086211
WO-A-2008/038147
US-A1- 2008 069 779
  
  • MARAMALDI G ET AL: "POTASSIUM AZELOYL DIGLYCINATE: A MULTIFUNCTIONAL SKIN LIGHTENER" COSMETICS & TOILETRIES, WHEATON, IL, US, vol. 117, no. 3, 1 March 2002 (2002-03-01), page 43/44,46,48,50, XP009054339 ISSN: 0361-4387
  • RIGANO, LUIGI ET AL: "Problem skin: physiological and hygienic treatments" COSMETIC TECHNOLOGY (MILANO, ITALY) , 8(5), 17-25 CODEN: CTECFI; ISSN: 1127-6312, 2005, XP008100138
  
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description


[0001] The present invention relates to compositions containing chitosan, a chitosan derivatives which is hydroxyalkyl chitosan or a physiologically acceptable salt thereof, and a short-medium chain dicarboxylic acid amide, or a physiologically acceptable salt thereof, for the preparation of a medicament, or a medical device, or a sanitary product, or a cosmetic, forming a film after application onto the skin of the face and of other affected areas, useful for protecting skin in rosacea, a chronic inflammatory condition of the skin, and other skin conditions characterized by teleangectasia, like couperose and leg teleangectasia.

BACKGROUND OF THE INVENTION



[0002] Rosacea is a common but often misunderstood condition that is estimated to affect over 13 million people worldwide (Plewig & Jansen in: Fitzpatrick's Dermatology in General Medicine. Freedberg et al. Eds., 6th ed., McGRAW-HILL pub., NY 2003, p. 688). It affects white-skinned people of Celtic or northern European descent, and has been named the 'curse of the Celts'. It is rarer in dark-skinned people, like American and African blacks.

[0003] It begins as erythema (flushing and redness, also called "couperose") on the central face and across the cheeks, nose, or forehead but can also less commonly affect the neck and chest. As rosacea progresses, other symptoms can develop such as semi-permanent erythema, teleangiectasia (dilation of superficial blood vessels on the face), red domed papules (small bumps) and pustules, red gritty eyes, burning and stinging sensations, and in some advanced cases, a red lobulated nose (rhinophyma). The disorder can be confused with, and co-exist with acne vulgaris and/or seborrhoeic dermatitis. Rosacea affects both sexes, but is almost three times more common in women, is common in the third and fourth decade and peaks between the ages of 40 and 50 years. The presence of rash on the scalp or ears suggests a different or co-existing diagnosis, as rosacea is primarily a facial diagnosis.

[0004] The pathogenesis of rosacea in unknown, and various factors have been suspected to contribute to this condition. Among the various factors, the following have been claimed to play a role: degenerative changes of the perivascular/ vascular collagen, that lead to small vessel dilatation resulting in flushing, teleangiectasia, erithema; perivascular leakage of potentially inflammatory substances; abnormal tissue response to cytokines and other mediators; use of topical drugs (corticosteroids). Exposure to temperature extremes can cause the face to become flushed as well as strenuous exercise, heat from sunlight, severe sunburn, cold wind, moving from cold to hot environment. There are also some foods and drinks that can trigger flushing, these include alcohol, caffeine (hot tea and coffee), and spicy food. Microorganism also have been claimed to contribute to the development or complicate rosacea, like Demodex folliculorum, Helicobacter pylori or Propionibacterium acnes.

[0005] Treatment of rosacea is inconclusive. Systemic or topical treatments include antibiotics, metronidazole and antifungals; retinoids, some beta blockers, spironolactone. No causal treatment has ever been proposed, and lifelong symptomatic treatment is often necessary, as just few cases may go into a permanent remission of the symptoms. Long term treatment of rosacea is limited by the intrinsic toxicity of drugs.

[0006] Leg teleangectasia consists in very thin varicose capillaries, with calibre within 0,1 and 1 mm, that are classified as follows:
  1. 1) Teleangectasia due to venous insufficiency, accompanied by other clinical signs of venous insufficiency. They are localized at the foot back, retromalleolar region, legs, and at the medial thigh surface.
  2. 2) Teleangectasia due to hormonal abnormalities, localized at the medial and anterolateral thigh surface. They spontaneously occur during menarche, menopause, pregnancy or under contraceptive treatment.
  3. 3) Very thin teleangectasia due to constitutional weakness of the capillary system, mainly at the distal portion of the legs. This is triggered by UV radiation, and by hot and cold temperature.
  4. 4) Matting type teleangectasia
  5. 5) Reticular varicous veins: in most cases they represent the nourishing veins for the districts that are interested by telengectasia.


[0007] No satisfactory treatment exists for leg teleangectasia and the only possible treatment is aesthetic surgery.

[0008] Thus, there is an unsatisfied need of safe and active medical tools to protect a skin that is unusually vulnerable to chemical and physical insults.

[0009] Chitosan and its derivatives are amino-polysaccharides, derived from the chitin extracted from the exoskeleton of the crustaceans, known in the art for their use in different preparations. KR20020084672 discloses chitosan as an ingredient of microspheres, useful as a carrier for separation of proteins or peptides; KR20020048534 reports chitosan as an ingredient of a pack composition for skin massage, including paraffin wax as an effective component; JP2005306746 is teaching the use of chitosan to obtain a wrinkle therapeutic agent as an ingredient of gel-like or spongy preparations of botulinus toxin. WO2005055924 reports chitosan derivatives as ingredients of hydrogels useful for cavity-filling wound dressings. JP2004231604 teaches compositions of chitosans having a high deacetylation degree, as an ingredient of a carrier sheet with a porous spongy texture. WO03042251 discloses compositions comprising chitosan in the form of a network of nano-sized fibres. WO02057983 discloses a multilayered, air gap sheet of chitosan with a regular lamellar structure which retains drugs for a prolonged period of time; JP11060605 teaches an amphiphilic chitosan derivative which can be used as dispersion stabilizer or emulsifier in a drug for application to skin. Finally, EP1303249, discloses a nail varnish composition containing at least one antimycotic agent and an hydroxyalkyl or a carboxyalkyl chitosan, whereas WO2004/112814 discloses a nail restructuring composition based on one herb extract from the genus Equisetum in combination with hydroxypropyl chitosan.

DESCRIPTION OF THE INVENTION



[0010] It has now surprisingly been found that preparations containing chitosan or its derivatives, which are hydroxyalkyl chitosans, and at least the amide of a short-medium chain (from 6 to 12 carbon atoms) aliphatic dicarboxylic acid may form an elastic film onto the skin, after application and drying, suitable to protect the skin from chemical or physical insults. The two components of the film, saccharidic and lipidic, act in a synergistic way and have a protective activity superior to that of the two components alone.

[0011] The film forming compositions according to the present invention may easily be sprayed onto the skin surface, by allowing quick drying and easy formation of an elastic film, that avoids bothersome sensation of oily skin. The film forming compositions according to the present invention may also be applied on the skin by gently massage. The film formed after drying protects the skin from the insult of both hot and cold temperature, decreases the inflammation due to ultraviolet radiation and prevents the growth of microorganisms by coating them and inhibiting their vital functions.

[0012] The object of the present invention is thus represented by a pharmaceutical and/or cosmetic composition containing:
  1. (A) at least chitosan, a chitosan derivative which is hydroxyalkyl alkyl chitosan and/or a physiologically acceptable salt thereof, and;
  2. (B) at least a C6-C12-dicarboxylic acid amide and/or a physiologically acceptable salt thereof.


[0013] Said composition is useful to form a film after application onto the skin and drying, that protects the skin of the face and the other areas affected byrosacea as well as by other skin conditions characterized by teleangectasia.

[0014] Chitosan derivatives are hydroxyalkyl chitosans, such as hydroxypropyl chitosan, being the claimed water soluble chitosans derivatives.

[0015] Among the C6-C12-dicarboxylic acids, C8-C16-dicarboxylic acids are particularly preferred, Cg-dicarboxylic acids being the most preferred; according to additional preferred ambodiments, such dicarboxylic acids are linear and/or alkyl acids.

[0016] The C6-C12-dicarboxylic acid amide which is used for the purposes of the present invention is preferably represented by the following formula:

        ROC-(CH2)n-COR

wherein:

"n" is comprised between 4 and 10, preferably between 6 and 8 and, more preferably, it is 7;

R is a -N(R')(R'') group, wherein:

R' is H or a C1-C4-alkyl group, and

R" is H, a C1-C4-alkyl group or a C1-C4-carboxy group.



[0017] According to preferred embodiments, said C1-C4-alkyl groups are methyl or ethyl whereas said C1-C4-carboxy group is carboxy methyl.

[0018] The preferred C6-C12-dicarboxylic acid is azelaic acid. Among C6-C12-dicarboxylic acid amides, azelaic acid amides, such as azeloyl diglycine, are thus preferred, and may be in form of a salt, preferably a sodium or potassium salt, such as potassium azeloyl diglycinate.

[0019] The composition according to the present invention may be applied by a gently massage on the skin, or may be sprayed by allowing the formation of an elastic film after drying. The composition according to the present invention allows a long lasting intimate contact and continuous protection of the skin for many hours after the application.

[0020] Compositions according to the present invention are in the form are in the form of liquid, semiliquid or semisolid preparations, including solutions, suspensions, lotions, emulsions, colloids, creams, gels, with a content in component A from 0.1 to 10 wt.% (percentages by weight are given with respect to the whole preparation), preferably from 0.2 to 5 wt.%, more preferably from 0.25 to 2.0 wt.% and with a content in component B from 0.1 to 30 wt.% (percentages by weight are given with respect to the whole preparation), preferably from 0.25 to 25 wt.%, more preferably from 0.5 to 20 wt.%.

[0021] Compositions according to the present invention are superior to the conventional formulations, in that they leave an uniform and invisible film. Moreover, compositions according to the present invention do not dirty, do not dry like gels and lotions do, and do not give bothersome sensation when applied, like other rigid film preparations do.

[0022] Pharmaceutical compositions are prepared according to conventional technique, using compatible excipients, adjuvants and/or pharmaceutically or cosmetically acceptable carriers, and may contain, in combination, other active principles with complementary or, in any case, useful activity.

[0023] Examples of these compositions prepared according to the present invention include: solutions, emulsions, suspensions, colloids, creams, gels, for application to affected skin.

[0024] The compositions according to the present invention may contain one or more additional ingredients selected from solvents, sunscreens, skin-conditioning agents, emollients, moisturizers, emulsifying agents, viscosity-increasing agents, UV-A filters, plant extracts, antioxidants.

[0025] The pharmaceutical compositions and the uses of the present invention will now be more fully described by the following examples. It should, however, be noted that such examples are given by way of illustration.

Example 1



[0026] An oil in water cream having the following w/w % composition was prepared:
1. POTASSIUM PALMITOYL HYDROLYZED WHEAT PROTEIN 1.00%
2. GLYCERYL STEARATE 2.00%
3. CETEARYL ALCOHOL 2.00%
4. GLYCERYL STEARATE SE 1.00%
5. DICAPRYLYL ETHER 4.00%
6. ETHYLHEXYL METHOXYCINNAMATE 4.00%
.7. BUTYL METHOXYDIBENZOYLMETHANE 1.00%
8. LECITHIN 0.02%
9. TOCOPHEROL 0.001%
10. ASCORBYL PALMITATE 0.001%
11. CITRIC ACID 0.001%
12. TOCOPHERYL ACETATE 0.50%
13. PURIFIED WATER 81.00%
14. HYDROXYPROPYL CHITOSAN 0.50%
15. XANTHAN GUM 0.50%
16. DENATURATED ETHYL ALCOHOL 1.00%
17. PHENETHYL ALCOHOL 0.50%
18. CAPRYLYL GLYCOL 0.50%
19. POTASSIUM AZELOYL DIGLYCINATE 0.50%

Preparation



[0027] 

Phase A: Hydroxypropyl chitosan was dispersed in ca. 50%wt of total water until a clear solution was obtained. The solution was heated at 65°C ± 2°C and Xanthan gum was added and stirred until a homogenous solution was obtained.

Phase B: Potassium palmitoyl, Glyceryl Stearate, Cetearyl Alcohol, Glyceryl Stearate SE, Dicaprylyl Ether, Ethylehexyl methoxycinnamate, Butyl methoxydibenzoylmethane, Lecithin, Tocopherol, Ascorbyl Palmitate, Citric Acid and Tocopheryl Acetate were mixed together and heated at 65°C ± 2°C.



[0028] Phase B was added to Phase A under agitation (turbo) to allow the emulsification. The resulting emulsion was cooled to 35°C ± 2°C under continuous mixing.

[0029] Caprylyl Glycol dissolved into Phenethyl Alcohol, Potassium Azeloyl Diglycinate dissolved in the rest of purified water (50%wt) and Ethyl Alcohol were mixed into the emulsion at the end of preparation. The product was kept under gentle agitation until a homogenous oil in water cream was obtained.

Example 2



[0030] An oil in water cream having the following w/w % composition was prepared:
1. POTASSIUM PALMITOYL HYDROLYZED WHEAT PROTEIN 3.00%
2. GLYCERYL STEARATE 5.00%
3. CETEARYL ALCOHOL 5.00%
4. GLYCERYL STEARATE SE 3.00%
5. DICAPRYLYL ETHER 6.00%
6. ETHYLHEXYL METHOXYCINNAMATE 6.00%
7. BUTYL METHOXYDIBENZOYLMETHANE 3.00%
8. LECITHIN 0.04%
9. TOCOPHEROL 0.01%
10. ASCORBYL PALMITATE 0.01%
11. CITRIC ACID 0.01%
12. TOCOPHERYL ACETATE 1.00%
13. PURIFIED WATER 59.93%
14. HYDROXYPROPYL CHITOSAN 1.00%
15. XANTHAN GUM 1.00%
16. DENATURATED ETHYL ALCOHOL 3.00%
17. PHENETHYL ALCOHOL 1.00%
18. CAPRYLYL GLYCOL 1.00%
19. POTASSIUM AZELOYL DIGLYCINATE 1.00%

Preparation



[0031] The formulation was prepared by using the same method described for Example 1.

Example 3



[0032] An oil in water cream having the following w/w % composition was prepared:
1. POTASSIUM PALMITOYL HYDROLYZED WHEAT PROTEIN 2.00%
2. CETEARYL ALCOHOL 5.00%
3. GLYCERYL STEARATE SE 3.00%
4. DICAPRYLYL ETHER 5.00%
5. ETHYLHEXYL METHOXYCINNAMATE 4.00%
6. LECITHIN 0.04%
7. ASCORBYL PALMITATE 0.01%
8. CITRIC ACID 0.01%
9. TOCOPHERYL ACETATE 1.00%
10. PURIFIED WATER 72.94%
11. HYDROXYPROPYL CHITOSAN 1.00%
12. XANTHAN GUM 1.00%
13. DENATURATED ETHYL ALCOHOL 3.00%
14. PHENETHYL ALCOHOL 1.00%
15. POTASSIUM AZELOYL DIGLYCINATE 1.00%

Preparation



[0033] 

Phase A: Hydroxypropyl chitosan was dispersed in ca. 50%wt of total water until a clear solution was obtained. The solution was heated at 65°C ± 2°C and Xanthan gum was added and stirred until a homogenous solution was obtained.

Phase B: Potassium palmitoyl, Cetearyl Alcohol, Glyceryl Stearate SE, Dicaprylyl Ether, Ethylehexyl methoxycinnamate, Lecithin, Ascorbyl Palmitate, Citric Acid and Tocopheryl Acetate were mixed together and heated at 65°C ± 2°C.



[0034] Phase B was added to Phase A under agitation (turbo) to allow the emulsification. The resulting emulsion was cooled to 35°C ± 2°C under continuous mixing.

[0035] Phenethyl Alcohol, Potassium Azeloyl Diglycinate dissolved in the rest of purified water (50%wt) and Ethyl Alcohol were mixed into the emulsion at the end of preparation. The product was kept under gentle agitation until a homogenous oil in water cream was obtained.

Example 4



[0036] An oil in water cream having the following w/w % composition was prepared:
1. POTASSIUM PALMITOYL HYDROLYZED WHEAT PROTEIN 2.00%
2. GLYCERYL STEARATE 4.00%
3. CETEARYL ALCOHOL 4.00%
4. GLYCERYL STEARATE SE 2.00%
5. DICAPRYLYL ETHER 5.00%
6. ETHYLHEXYL METHOXYCINNAMATE 8.00%
7. BUTYL METHOXYDIBENZOYLMETHANE 2.00%
8. BIS-ETHYLHEXYLOXYPHENOL METHOXYPHENYL TRIAZINE 3.00%
9. LECITHIN 0.040%
10. TOCOPHEROL 0.002%
11. ASCORBYL PALMITATE 0.002%
12. CITRIC ACID 0.002%
13. TOCOPHERYL ACETATE 0.20%
14. HYDROXYPROPYL CHITOSAN 1.00%
15. XANTHAN GUM 0.30%
16. DENATURATED ETHYL ALCOHOL 2.00%
17. PHENETHYL ALCOHOL 0.50%
18. CAPRYLYL GLYCOL 0.50%
19. POTASSIUM AZELOYL DIGLYCINATE 0.50%
20. PURIFIED WATER q.s to 100.00%

Preparation



[0037] The preparation was made as in Example 1. A homogenous oil in water cream was obtained.

Example 5



[0038] A comparative evaluation of the inhibition of VEGF (Vascular Endothelial Growth Factor) release on human 3D artificial skin was tested by the preparation as per the Example 4, compared to two different preparations, respectively named LPOL2899A (same as per the Example 4, but not containing POTASSIUM AZELOYL DIGLYCINATE), LPOL2899B (same as per the Example 4, but not containing HYDROXYPROPYL CHITOSAN) and LPOL2899C (same as per the Example 4, but not containing either POTASSIUM AZELOYL DIGLYCINATE or HYDROXYPROPYL CHITOSAN).

[0039] The effect of the four preparations was tested on the inhibition of Vascular Endothelial Growth Factor (VEGF) production induced by a pro-inflammatory stimulus on 3D human epidermis. VEGF is a strong angiogenic protein that significantly influences the vessels permeability and is constitutively expressed in keratinocytes, i.e. the cells of the skin. Under stressful conditions, such as exposure to soluble inflammation mediator like IL-1 alpha, epidermal keratinocytes increase the synthesis and release of VEGF. Epidermis units have been treated with IL-1α in the cell medium to induce an increase in the VEGF synthesis, and at the same time treated applying the investigated samples undiluted on the epidermis corneous layer. Following 24 h treatment, the cell culture medium below the epidermis units was collected and analyzed for the VEGF content through an ELISA assay.

[0040] The tested samples were the preparation as per the Example 4 and the two comparative preparations LPOL2899A and LPOL2899B. Skin units treated with IL-1α only have been used as positive controls. The experiment was carried out in three replicas.

[0041] In vitro test system employed consists of a tridimensional artificial system of human epidermis (Mattek, USA) i. e. a reconstructed artificial human skin model comprising normal human epidermal keratinocytes, growing as an integrated three-dimensional cell culture model, perfectly mimicking the human skin in vitro. The model exhibits normal barrier functions (presence of a differentiated stratum corneum).

[0042] About 20 mg of each undiluted sample have been applied on epidermis unit in three replicas, the exposure 30' following the products application, epidermis units, except the controls, have been treated for 2 h with 500 pg/ml of IL-1α (Prospec) in the cell medium, to improve the VEGF synthesis.

[0043] After 2 h the cel medium has been removed and changed. The incubation of the samples has been carried up to 24 hours at 37°C, 5% CO2.

[0044] As positive control epidermis units treated with IL-1 α only have been used. At the end of the exposure period, the products were removed, the tissue gently washed with phosphate buffer (PBS) for further MTT and viability assay, and the culture medium have been collected for VEGF assay.

[0045] VEGF release assay following IL-1α treatment, 500 pg/ml, with and without treatment with the samples is reported in the following table.
SampleVEGF pg/ml (DS%)% inhibition
Preparation of Example 4 + 500pg/ml IL-1α 313,21 (26,9) 46,4
LPOL 2899A + 500pg/ml IL-1α 386,03 (4,6) 33,9
LPOL 2899B + 500pg/ml IL-1α 433,86 (6,9) 25,7
LPOL 2899C + IL-1α 477,25 (4,1) 18,3
500pg/ml IL-1α (positive control) 583,93 (7,5) --------


[0046] The preparation containing the vehicle, but not the two ingredients potassium azeloyl diglycinate and hydroxypropyl chitosan, inhibited the IL-1 α induced VEGF release by only 18%. the effect of the preparation containing hydroxypropyl chitosan was 25.7% inhibition and that of the preparation containing potassium azeloyl diglycinate was 33.9% inhibition. The preparation as per the Example 4 had the strongest inhibitory effect (46.4% inhibition) confirming a synergistic activity of the two components on the protection of skin against the insult of IL-1 α.


Claims

1. A composition containing:

(A) at least chitosan, a hydroxyalkyl chitosan and/or a physiologically acceptable salt thereof, and;

(B) at least a linear and/or alkyl C6-C12-dicarboxylic acid amide and/or a physiologically acceptable salt thereof.


 
2. A composition according to claim 1, characterized in that said hydroxyalkyl chitosan is water soluble.
 
3. A composition according to claim 1, characterized in that said hydroxyalkyl chitosan is hydroxypropyl chitosan.
 
4. A composition according to claim 1, characterized in that the physiologically acceptable salt of said chitosan, hydroxyalkyl chitosan and/or C6-C12-dicarboxylic acid amide is a sodium and/or potassium salt.
 
5. A composition according to claim 1, characterized in that said C6-C12-dicarboxylic acid is a C8-C10-dicarboxylic acid, preferably a C9-dicarboxylic acid.
 
6. A composition according to claim 1, characterized in that said dicarboxylic acid is azelaic acid.
 
7. A composition according to claim 1, characterized in that said C6-C12-dicarboxylic acid amide has the following formula:

        ROC-(CH2)n-COR

wherein:

• n is comprised between 4 and 10, preferably between 6 and 8 and, more preferably, it is 7;

• R is a -N(R')(R'') group, wherein:

• R' is H or a C1-C4-alkyl group, and

• R" is H, a C1-C4-alkyl group or a C1-C4-carboxy group.


 
8. A composition according to claim 7, characterized in that said C1-C4-alkyl group is methyl and/or ethyl and said C1-C4-carboxy group is carboxy methyl.
 
9. A composition according to claim 1, characterized in that said C6-C12-dicarboxylic acid amide is azeloyl diglycine.
 
10. A composition according to claim 1, characterized in that said C6-C12-dicarboxylic acid amide salt is potassium azeloyl diglycinate.
 
11. A composition according to claim 1, characterized in that component (A) is present in amounts of from 0.1 to 10%, preferably from 0.2 to 5%, more preferably from 0.25 to 2.0%, with respect to the weight of the whole composition.
 
12. A composition according to claim 1, characterized in that component (B) is present in amounts of from 0.1 to 30%, preferably from 0.25 to 25%, more preferably from 0.5 to 20 wt%, with respect to the weight of the whole composition.
 
13. A composition according to claim 1, characterized by being in liquid, semiliquid or semisolid form, including solution, suspension, lotion, emulsion, colloid, cream or gel.
 
14. A composition according to claim 1, characterized by containing pharmaceutically and/or cosmetically acceptable active ingredients, excipients, adjuvants and/or carriers.
 
15. A composition according to any claims 1 to 14, for use in the treatment and/or prevention of rosacea.
 
16. A composition according to any of claims 1 to 14, for use in the treatment and/or prevention of teleangectasia, preferably leg teleangectasia.
 
17. A composition according to any of claims 1 to 14, for use in the treatment and/or prevention of couperose.
 


Ansprüche

1. Zusammensetzung umfassend:

(A) zumindest Chitosan, ein Hydroxyalkylchitosan und/oder ein physiologisch annehmbares Salz daraus; und

(B) zumindest ein lineares und/oder Alkyl-C6-C12-Dicarbonsäureamid und/oder ein physiologisch annehmbares Salz daraus.


 
2. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass das Hydroxyalkylchitosan wasserlöslich ist.
 
3. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass das Hydroxyalkylchitosan Hydroxypropylchitosan ist.
 
4. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass das physiologisch annehmbares Salz des Chitosans, Hydroxyalkylchitosans und/oder C6-C12-Dicarbonsäureamids ein Natrium- und/oder Kaliumsalz ist.
 
5. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass die C6-C12-Dicarbonsäure eine C8-C10-Dicarbonsäure, vorzugsweise eine C9-Dicarbonsäure ist.
 
6. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass die Dicarbonsäure Azelainsäure ist.
 
7. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass das C6-C12-Dicarbonsäureamid die folgende Formel aufweist:

        ROC-(CH2)n-COR

wobei:

- n zwischen 4 und 10 umfasst ist, vorzugsweise zwischen 6 und 8 und besonders bevorzugt 7 ist;

- R eine -N(R')(R")-Gruppe ist, wobei:

- R' H oder eine C1-C4-Alkylgruppe ist und

- R" H, eine C1-C4-Alkylgruppe oder eine C1-C4-Carboxygruppe ist.


 
8. Zusammensetzung gemäß Anspruch 7, dadurch gekennzeichnet, dass die C1-C4-Alkylgruppe Methyl und/oder Ethyl und die C1-C4-Carboxygruppe Carboxymethyl ist.
 
9. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass das C6-C12-Dicarbonsäureamid Azeloyl-Diglycin ist.
 
10. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass das C6-C12-Dicarbonsäureamidsalz ein Kaliumazeloyl-Diglycinat ist.
 
11. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass Komponente (A) in Mengen von 0,1 bis 10%, vorzugsweise von 0,2 bis 5%, besonders bevorzugt von 0,25 bis 2,0% in Bezug auf das Gewicht der gesamten Zusammensetzung vorliegt.
 
12. Zusammensetzung gemäß Anspruch 1, dadurch gekennzeichnet, dass Komponente (B) in Mengen von 0,1 bis 30%, vorzugsweise von 0,25 bis 25%, besonders bevorzugt von 0,5 bis 20 Gew.-%, in Bezug auf das Gewicht der gesamten Zusammensetzung vorliegt.
 
13. Zusammensetzung gemäß Anspruch 1, gekennzeichnet durch das Vorliegen in flüssiger, semi-flüssiger oder semi-fester Form, einschließlich Lösung, Suspension, Lotion, Emulsion, Kolloid, Creme oder Gel.
 
14. Zusammensetzung gemäß Anspruch 1, gekennzeichnet durch Beihnalten pharmazeutisch und/oder kosmetisch annehmbarer aktiver Bestandteile, Bindemittel, Hilfsstoffe und/oder Trägerstoffe.
 
15. Zusammensetzung gemäß einem der Ansprüche 1 bis 14 zur Verwendung in einer Behandlung und/oder Vorbeugung von Rosacea.
 
16. Zusammensetzung gemäß einem der Ansprüche 1 bis 14 zur Verwendung in einer Behandlung und/oder Vorbeugung von Teleangiektasie, vorzugsweise Bein-Teleangiektasie.
 
17. Zusammensetzung gemäß einem der Ansprüche 1 bis 14 zur Verwendung in einer Behandlung und/oder Vorbeugung von Couperose.
 


Revendications

1. Composition contenant :

(A) au moins un chitosane, un chitosane hydroxyalkylé et/ou un sel physiologiquement acceptable de ceux-ci ; et

(B) au moins un amide d'acide dicarboxylique alkylique en C6 à C12 et/ou linéaire et/ou un sel physiologiquement acceptable de ceux-ci.


 
2. Composition selon la revendication 1, caractérisée en ce que ledit chitosane hydroxyalkylé est soluble dans l'eau.
 
3. Composition selon la revendication 1, caractérisée en ce que ledit chitosane hydroxyalkylé est le chitosane hydroxypropylé.
 
4. Composition selon la revendication 1, caractérisée en ce que le sel physiologiquement acceptable dudit chitosane, dudit chitosane hydroxyalkylé et/ou dudit amide d'acide dicarboxylique alkylique en C6 à C12 est un sel de sodium et/ou de potassium.
 
5. Composition selon la revendication 1, caractérisée en ce que ledit acide dicarboxylique en C6 à C12 est un acide dicarboxylique en C8 à C10, de préférence un acide dicarboxylique en C9.
 
6. Composition selon la revendication 1, caractérisée en ce que ledit acide dicarboxylique est l'acide azélaïque.
 
7. Composition selon la revendication 1, caractérisée en ce que ledit amide d'acide dicarboxylique en C6 à C12 répond à la formule suivante :

        ROC-(CH2)n-COR

dans laquelle :

• n est compris entre 4 et 10, de préférence entre 6 et 8, plus préférablement c'est 7 ;

• R est un groupe -N(R')(R"), où :

• R' est H ou un groupe alkyle en C1 à C4, et

• R" est H, un groupe alkyle en C1 à C4 ou un groupe carboxy en C1 à C4.


 
8. Composition selon la revendication 7, caractérisée en ce que ledit groupe alkyle C1 à C4 est un groupe méthyle et/ou éthyle et ledit groupe carboxy C1 à C4 est un carboxyméthyle.
 
9. Composition selon la revendication 1, caractérisée en ce que ledit amide d'acide dicarboxylique en C6 à C12 est l'azéloyldiglycine.
 
10. Composition selon la revendication 1, caractérisée en ce que ledit sel d'amide d'acide dicarboxylique en C6 à C12 est le diglycinate d'azéloyle potassique.
 
11. Composition selon la revendication 1, caractérisée en ce que le composant (A) est présent en des quantités de 0,1 à 10 %, de préférence de 0,2 à 5 %, plus préférablement de 0,25 à 2,0 %, par rapport au poids de la composition totale.
 
12. Composition selon la revendication 1, caractérisée en ce que le composant (B) est présent en des quantités de 0,1 à 30 %, de préférence de 0,25 à 25 %, plus préférablement de 0,5 à 20 % en poids, par rapport au poids de la composition totale.
 
13. Composition selon la revendication 1, caractérisée en ce qu'elle est sous une forme liquide, semi-liquide ou semi-solide, y compris une solution, une suspension, une lotion, une émulsion, un colloïde, une crème ou un gel.
 
14. Composition selon la revendication 1, caractérisée en ce qu'elle contient des principes actifs, des excipients, des adjuvants et/ou des véhicules pharmaceutiquement et/ou cosmétiquement acceptables.
 
15. Composition selon l'une quelconque des revendications 1 à 14, pour une utilisation dans le traitement et/ou la prévention d'une rosacée.
 
16. Composition selon l'une quelconque des revendications 1 à 14, pour une utilisation dans le traitement et/ou la prévention d'une télangiectasie, de préférence d'une télangiectasie sur les jambes.
 
17. Composition selon l'une quelconque des revendications 1 à 14, pour une utilisation dans le traitement et/ou la prévention d'une couperose.
 






Cited references

REFERENCES CITED IN THE DESCRIPTION



This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description




Non-patent literature cited in the description