阅读说明：本技术 化妆品/皮肤病学组合物 (Cosmetic/dermatological composition ) 是由 丹尼斯·巴里托 于 2019-12-30 设计创作，主要内容包括：本发明涉及一种药学或皮肤病学组合物并且涉及其作为药物的用途。本发明还涉及一种化妆品或皮肤病学组合物并且涉及包含本发明的所述组合物的护理试剂盒。本发明具体地应用于化妆品、药物和兽医领域中。(The present invention relates to a pharmaceutical or dermatological composition and to its use as a medicament. The invention also relates to a cosmetic or dermatological composition and to a care kit comprising said composition of the invention. The invention finds particular application in the cosmetic, pharmaceutical and veterinary fields.)

1. A pharmaceutical or dermatological composition for use as a medicament, the composition comprising:

-biocompatible polymers of the general formula (I)

AaXxYy (I)

Wherein:

a represents a monomer, and A represents a monomer,

x represents R₁COOR₂or-R₉(C＝O)R₁₀The radical(s) is (are),

y represents an O-sulfonate group or an N-sulfonate group corresponding to one of the following formulae: -R₃OSO3R₄、-R₅NSO3R₆、R₇SO₃R₈Wherein:

R₁、R₃、R₅and R₉Independently represents an optionally branched and/or unsaturated aliphatic hydrocarbon chain optionally containing one or more aromatic rings, in addition to benzylamine and benzylaminosulfonate, R₂、R₄、R₆And R₈Independently represents a hydrogen atom or a cation,

R₇and R₁₀Independently represents a bond, an optionally branched and/or unsaturated aliphatic hydrocarbon chain,

a represents the number of the monomers,

x represents the substitution rate of the group X for the monomer A,

y represents a substitution rate of the group Y for the monomer A; and

-hyaluronic acid.

2. A cosmetic, non-therapeutic or dermatological use of a composition comprising:

-biocompatible polymers of the general formula (I)

AaXxYy (I)

Wherein:

a represents a monomer, and A represents a monomer,

x represents R₁COOR₂or-R₉(C＝O)R₁₀The radical(s) is (are),

y represents an O-sulfonate group or an N-sulfonate corresponding to one of the formulaeGroup (b): -R₃OSO₃R₄、-R₅NSO₃R₆、R₇SO₃R₈Wherein:

R₁、R₃、R₅and R₉Independently represents an optionally branched and/or unsaturated aliphatic hydrocarbon chain optionally containing one or more aromatic rings, in addition to benzylamine and benzylaminosulfonate, R₂、R₄、R₆And R₈Independently represents a hydrogen atom or a cation,

R₇and R₁₀Independently represents a bond, an optionally branched and/or unsaturated aliphatic hydrocarbon chain,

a represents the number of the monomers,

x represents the substitution rate of the group X for the monomer A,

y represents a substitution rate of the group Y for the monomer A; and

-hyaluronic acid.

3. The composition for application or use according to claim 1 or claim 2, wherein the same or different monomer a is selected from a sugar, an ester, an alcohol, an amino acid, a nucleotide, a nucleic acid, a protein, or a derivative thereof.

4. The composition for use or application according to any one of claims 1 to 3, wherein the same or different monomers A are selected from sugars or derivatives thereof.

5. The composition for use or application according to any of claims 1 to 4, wherein up to 20% of the monomers A are independently monomers of the formula:

wherein R is₉And R₁₀Independently represents an oxygen atom, an optionally branched and/or unsaturated aliphatic hydrocarbon chain, independentlyHeteroaryl comprising one or more oxygen and/or nitrogen atoms, aldehyde functional groups, carboxylic acid groups, diols, substituted diols, formula-R₁₁-(X)n-R₁₂Wherein R is₁₁Represents optionally branched and/or unsaturated C₁To C₄An aliphatic carbon chain, X represents a heteroatom selected from oxygen and nitrogen, n is an integer between 1 and 4, and R₁₂Are a hydrogen atom, an optionally branched and/or unsaturated aliphatic hydrocarbon chain, a heteroaryl group independently comprising one or more oxygen atoms and/or nitrogen atoms, an aldehyde functional group, a carboxylic acid group, a diol, a substituted diol.

6. The composition for application or use according to any one of claims 1 to 5, wherein the amount of monomer "a" is such that the mass of the polymer of formula (I) is greater than or equal to 3000 daltons.

7. The composition for application or use according to any one of claims 1 to 6, wherein the substitution rate "x" is between 10% and 150%.

8. The composition for application or use according to any of the preceding claims, wherein the substitution rate "y" is between 10% and 170%.

9. The composition for application or use according to any one of the preceding claims, wherein the group R is selected from linear or branched alkyl, allyl or aryl.

10. The composition for application according to any one of the preceding claims, wherein the biocompatible polymer further comprises a chemical functional group Z, which is different from X and Y and is capable of providing the polymer with additional biological or physicochemical properties.

11. The composition for application according to claim 10, wherein the substitution rate "Z" of said group Z for all monomers a is between 1% and 50%.

12. The composition for application according to claim 10 or claim 11, wherein the group Z is a substance capable of providing improved solubility or lipophilicity to the polymer.

13. The composition for application according to claim 12, wherein said groups Z are the same or different and are selected from the group comprising: amino acids, fatty alcohols, ceramides or derivatives thereof, or indeed addressing nucleotide sequences.

14. The composition for use according to any one of claims 6 to 13, wherein the group R₉And R₁₀Independently and optionally substituted with a group Z.

15. The composition for use according to claim 1 or any one of claims 3 to 14 when dependent on claim 1, wherein the medicament is for the treatment of a tissue lesion and/or tissue desiccation and/or fibrosis.

16. The composition for use according to claim 1 or any one of claims 3 to 14 when dependent on claim 1, wherein the medicament is intended for the prevention and/or treatment of a disease and/or pathology selected from the group comprising fibrosis, histopathology, pathology and/or pathology of the locomotor system, retinal detachment, and/or treatment of age-related macular degeneration, dry age-related macular degeneration, wet age-related macular degeneration, tissue desiccation, mucosal desiccation, epidermolysis bullosa, periodontal disease, oral mucosal disease, burns, degenerative diseases.

17. The composition for use according to claim 1 or any one of claims 3 to 14 when dependent on claim 1, wherein the medicament is for the treatment of a skin lesion.

18. The composition for use according to claim 1 or any one of claims 3 to 14 when dependent on claim 1, wherein the medicament is for the treatment of a degenerative disease.

19. The composition for use according to claim 2 or any one of claims 3 to 14 when dependent on claim 2, wherein the non-therapeutic cosmetic use is an anti-ageing use and/or a use for protecting the skin from external aggressions and/or for treating and/or preventing skin ageing.

20. Use of a pharmaceutical composition comprising:

i. biocompatible polymers of the general formula (I)

AaXxYy (I)

Wherein:

a represents a monomer, and A represents a monomer,

x represents R₁COOR₂The radical(s) is (are),

y represents an O-sulfonate group or an N-sulfonate group corresponding to one of the following formulae: -R₃OSO3R₄、-R₅NSO3R₆、R₇SO₃R₈Wherein:

R₁、R₃、R₅and R₉Independently represents an optionally branched and/or unsaturated aliphatic hydrocarbon chain optionally containing one or more aromatic rings, in addition to benzylamine and benzylaminosulfonate, R₂、R₄、R₆And R₈Independently represents a hydrogen atom or a cation,

R₇and R₁₀Independently represents a bond, an optionally branched and/or unsaturated aliphatic hydrocarbon chain,

a represents the number of the monomers,

x represents the substitution rate of the group X for the monomer A,

y represents a substitution rate of the group Y for the monomer A; and

hyaluronic acid for use in the preparation of a medicament.

21. A cosmetic, non-therapeutic use of a composition comprising:

i. biocompatible polymers of the general formula (I)

AaXxYy (I)

Wherein:

a represents a monomer, and A represents a monomer,

x represents R₁COOR₂The radical(s) is (are),

y represents an O-sulfonate group or an N-sulfonate group corresponding to one of the following formulae: -R₃OSO3R₄、-R₅NSO3R₆、R₇SO₃R₈Wherein:

R₁、R₃、R₅and R₉Independently represents an optionally branched and/or unsaturated aliphatic hydrocarbon chain optionally containing one or more aromatic rings, in addition to benzylamine and benzylaminosulfonate, R₂、R₄、R₆And R₈Independently represents a hydrogen atom or a cation,

R₇and R₁₀Independently represents a bond, an optionally branched and/or unsaturated aliphatic hydrocarbon chain, a represents the number of monomers,

x represents the substitution rate of the group X for the monomer A,

y represents a substitution rate of the group Y for the monomer A; and

hyaluronic acid.

Technical Field

The present invention relates to a pharmaceutical or dermatological composition and to its use as a medicament or medical device.

The invention also relates to a cosmetic or dermatological composition and to a care kit comprising the composition of the invention.

The invention also relates to an anti-aging cosmetic or dermatological composition, and to a care kit comprising the composition of the invention.

The invention also relates to a cosmetic, dermatological hydration composition and to a care kit comprising the composition of the invention.

The invention also relates to an ophthalmic composition, in particular an ophthalmic composition for hydrating the cornea, and to a care kit comprising the composition of the invention.

The invention also relates to an anti-wrinkle cosmetic or dermatological composition, and to a care kit comprising the composition of the invention.

The invention also relates to a cosmetic or dermatological composition for use in the treatment of skin ageing for improving the appearance of the skin, and to a care kit comprising the composition of the invention.

The invention is particularly useful in the cosmetic, pharmaceutical and veterinary fields.

The invention is particularly useful in the fields of joint medicine and veterinary medicine, particularly for improving and promoting the locomotor function movements and restitution.

The invention is particularly useful in the pharmaceutical and veterinary fields of spinal locomotion, particularly for improving and facilitating locomotion and recovery of motor function.

The invention is used in the dental field, in particular for improving gingival and oral mucosa, fibrosis, such as muscle fibrosis, adhesions, fibrosis of the digestive system, fibrosis associated with surgery, cardiac fibrosis, brain fibrosis, for example as an antioxidant, for treating oxidative stress.

In the following description, references between brackets [ ] refer to the list of references set forth at the end of the text.

Background

The skin, which is not only the outer shell but also the organ itself, plays a vital role not only in protecting the body from external aggressions, but also in aesthetic and emotional level. The skin breathes, is sensitive to external aggressions and reacts to the general state of health and hormonal balance.

Human skin is composed of two components-the epidermis and the dermis. Hypodermal or subcutaneous connective tissue of widely varying thickness generally adheres functionally to the skin and is composed essentially of vascularized and innervated to a high degree of a fatty tissue that serves as the interface of underlying muscles and tendons. Suitable for sweat and sebaceous glands, skin appendages, hair and nails.

Healthy skin is skin that retains moisture. The skin is soft, firm, flexible and elastic. The dermis is composed of cellular structures with the main purpose of ensuring skin hydration. In the thin layer of epidermal, corneal cells, a protective keratin compound in the form of a "thousand layers" (or "thousands") acts as a barrier to retain moisture and to filter out moisture evaporation. The skin is composed of approximately 70% moisture, 1/5 which is the moisture stored in the body. Moisture flows from the dermis to the epidermis. A cell cushion (cellular cushion) composed of lipid-based fatty substances and more particularly ceramides prevents evaporation of water. This is the substance that determines the natural hydration factor of the epidermis. The normal hydration rate of moisture-retaining skin is between 13% and 15%. When this ratio drops to 10%, the skin will dehydrate. When the epidermis is not properly hydrated, the skin loses its suppleness and becomes dull due to lack of moisture or essential fatty acids.

The first visible signs related to age appear in texture, flexibility, color, clarity and appearance of wrinkles.

In the field of facial aesthetics, skin changes associated with age and hormonal regulation are often identified as skin atrophy, laxity, and weight gain. Atrophy corresponds to a significant thinning of the dermis and epidermis, resulting in a reduction in the number of epidermal cells and the thickness of dermal connective tissue, and a relaxation of the hypodermis and hypodermis (fat, muscle), resulting in skin redundancy and sagging. Laxity through visible collapse of the cheek and mandible lines and the area under the eyelids; as regards the thickening associated with weight gain with age, this is observed by swelling of the bottom of the face and neck.

These time-related signs of aging may be accelerated and amplified by lifestyles such as, inter alia, smoking, alcohol abuse, or exposure to sunlight. Said signs are also often accompanied by skin dryness and redness, which are associated with a loss of elasticity, resulting in a change in the quality of the skin tissue. The skin can wrinkle under mechanical pressure and take longer to recover and return to its original state. These visual signs are merely an extrinsic reflection of these internal changes related to the age of the skin tissue.

The decrease in epidermal thickness with age leads to a decrease in proliferation of basal layer cells, a decrease in the number of epidermal cell layers, alterations in the extracellular matrix of quantity, structure, tissue and function, both on proteins and on glycosaminoglycans (GAGs) and Proteoglycans (PGs), and the appearance of wrinkles.

Among these (GAGs), Hyaluronic Acid (HA) plays a central role in maintaining hydration at all levels of the skin layer, and the reduction of HA is associated with the appearance of wrinkles and with Heparan Sulfate (HS) in the natural balance regulating tissue homeostasis, ensuring a quadruple role in both epidermal and dermal or hypodermal tissues as an element for stabilizing, protecting the matrix architecture, storing and regulating the bioavailability of cellular communication factors in the microenvironment.

In order to reduce the adverse effects associated with alterations in skin and aging, many approaches have been sought to prevent, delay, improve various elements both in terms of proteins and GAG present in the skin. In particular, this may be a method which attempts to increase the synthesis, delay the degradation of endogenous products by introducing products which are able to substitute them but are more resistant to degradation, or else to introduce stimulators of matrix protein synthesis such as collagen or elastin, which also improve the properties of the skin at the mechanical and aesthetic level. Another possibility is to use surfactants which also have an immediate effect on the skin, reducing fine lines and wrinkles and smoothing the skin, but these effects are very short-term and superficial.

There are many cosmetic compositions, active ingredients, in the prior art for the treatment of skin aging. However, none of these compositions or none of these active ingredients is able to act in a lasting manner on the signs of ageing and/or is able to restore/improve the structure of the skin naturally.

Thus, in the prior art, there is a real need to find a compound and/or composition that makes it possible to effectively treat skin ageing and/or to improve the appearance of the skin in a lasting manner and/or to improve the structure of the skin.

There are also many cosmetic compositions, active ingredients, for treating skin ageing, the effects and/or benefits of which are time-limited, in particular due to their natural rate of elimination and/or environmental relevance, thus limiting the duration of the effect in relation to their presence on the area to be treated and/or on the skin.

Thus, there is a real need in the art to find compounds and/or compositions having an effect and/or benefit that is long-lasting, in particular compounds and/or compositions that make it possible to effectively treat skin ageing and/or to improve the appearance of the skin and/or to improve the structure of the skin in a lasting manner.

Furthermore, the known compositions and/or active ingredients are not effective in restoring and/or improving skin structure. In particular, the known compositions and/or active ingredients do not restore and/or improve the structure of the skin and/or effectively prevent skin ageing.

Furthermore, to be relatively effective, the known compositions and/or active ingredients require a large number of applications and/or a long duration of treatment and/or a high frequency of application, in particular on the skin. High application rates and/or high/long treatment durations may lead to skin irritation and possible allergic reactions.

Thus, in the prior art, there is a real need to find a compound and/or composition that makes it possible to effectively treat skin ageing and/or to improve the appearance of the skin, in particular allowing a limited number of applications to achieve an effect, in particular anti-ageing and/or improving the appearance of the skin.

Furthermore, the known compositions and/or active ingredients generally have a surface effect, for example only temporary, for example a few hours, not allowing a lasting and/or structural effect. Furthermore, the known compositions and/or active ingredients do not treat and/or compensate for the mechanisms and/or deficiencies caused by skin aging.

Hyaluronic acid is used, for example, in the cosmetic field as a hydrating compound, and also in the medical field, for example to treat vaginal or vulvar dryness. In particular, hyaluronic acid is used by means of injection, for example in the labial area, to re-swell and rehydrate the skin and restore the volume of the labia majora, which can protect the vulva and the vaginal orifice again, and also prevent the itching associated with such dryness. Hyaluronic acid is also used for the treatment of dry eye, dry hair and follicle rehydration, for example in the form of a gel or by microinjection, for example in cosmetic therapy alone or together with nutritional or protective cofactors. Hyaluronic acid may also be used in injections to improve sexual life in men by increasing their glands. Examples of the application and/or use of hyaluronic acid are specifically shown in the following documents: modified hyaluronic acid-based materials for biomedical applications (Modified hyaluronic acid based materials for biological applications), Tiwari S, Bahadur p., (Int J Biol macro) in the journal of biomacromolecules, month 1, 2019; 121:556-571.doi:10.1016/j.ijbiomac.2018.10.049. electronic edition 2018, 10 months, 12 days review [1 ]; hyaluronic acid, a promising living biomedical agent: recent updates to the effects of cosmetics and nutraceuticals and reviews of preclinical and clinical studies (Hyaluronic acid, a studying skin rejuvenated biomedicines: A review of recent updates and pre-clinical and clinical interventions on cosmetic and clinical effects.) Bukhari SNA, Roswandi NL, Waqas M, Habib H, Hussain F, Khan S, Sohail M, Ramli NA, Thu, HE, Hussain Z.International journal of biomacromolecules.2018, month 12; 120(Pt B) 1682-1695.doi:10.1016/j.ijbiomac.2018.09.188.doi:10.1016/j.ijbiomac.2018.09.188[2] and Reduction of post-operative adhesion development (Reduction of adhesion development) Diamond MP.Fertil Steril.2016 for 10 months; 106(5), 994-997.e1.doi:10.1016/j. fertnstert.2016.08.029. electronic version 2016, 9/month 10. overview [3 ]. However, despite many applications of hyaluronic acid, hyaluronic acid is used in injections, which requires precise medical procedures that cannot be performed daily by doctors as well as users.

Thus, there is a real need in the art to find a compound and/or composition that enables the effective treatment of tissue dryness, in particular skin dryness, in particular by topical application, for example by simple application to a tissue such as skin.

Thus, there is a real need in the art to find a compound and/or composition that can enable effective treatment of skin aging and/or can enable improvement in skin appearance by topical application, for example by simple application to tissue such as skin.

It is well known that over time, tissues, in particular the skin, undergo slow and irreversible development, resulting in anatomical, histological and functional changes.

There are many cosmetic compositions, active ingredients, in the prior art for the treatment of skin aging. However, none of these compositions or none of these active ingredients are capable of acting on and/or having a significant effect on mechanisms involving changes in the anatomy, histology and/or function of tissue, in particular skin.

Thus, in the prior art, there is a real need to find a compound and/or composition that is capable of enabling mechanisms that affect and/or have a significant effect on changes in anatomy, histology and/or function related to tissue, in particular skin.

Compounds, such as biocompatible polymers, which are used in the therapeutic field and which are capable of improving the tissue environment, are present in the prior art, and in particular, it is known to those skilled in the art that RGTA exerts an influence on the tissue repair and regeneration process by acting on the extracellular matrix, in particular protein elements which can protect the cellular and tissue microenvironment. The compounds are also well known for their pain-relieving and pain-relieving properties, as well as: possible anti-fibrotic activity (patent documents US06689741, US2014301972A1[4], Reversal of abnormal collagen production in Crohn 'S disease intestinal biopsy treated with a rejuvenating agent (Reversal of abnormal collagen production in Crohn' S disease intestinal biopsy), Alexaks C, Caruelle JP, Sezeur A, Cosnes J, Gendre JP, Mosnier H, Beaugerie L, Gallot D, Malafos M, Barritault D, Kern P. J. Gut.2004.1; 53; 85-90[5]), antioxidants (for stimulating apoptosis by polysaccharides), see the new pathway of mitochondrial prophase regulation (polysaccharide of collagen. beta. cholesterol. enteric, branched peptide of collagen. beta. cholesterol, branched peptide of collagen. E, branched peptide of collagen. beta. L, branched peptide of collagen, branched peptide of mitochondrial, branched peptide of collagen-beta. coli P. coli, branched peptide of collagen-beta. coli, branched peptide of collagen, branched peptide of L, branched peptide of L. coli, branched peptide of L, branched peptide of collagen, branched peptide of L, branched peptide of oligosaccharide, branched peptide of L, branched peptide of, caruelle JP, copy-Garcia D, Morin C. [ Cell Death differentiation (Cell Death Differ) ]2009, 5 months; 770 (5) to 81 Doi:10.1038/cdd.2009.9[6], Differential effects elicited by heparitin mimetics of the RGTA family in preventing oral mucositis without tumor protection (Differential effect triggered by the RGTA family of heparitin mimetics with no tumor protection Mangoni M, YueX, Morin C, Violot D, Frascogna V, Tao Y, Opolon P, Castaing M, Auperin A, Biti G, Barritault D, Vozenin-Brotons, Deutsch E, Bourhis J.International journal of radiation oncology Physics (Int J radiation Phys) 2009.7.2009 15; 74(4) 1242-50.doi 10.1016/J. ijrobp.2009.03.006[7]), healing (RGTA OTR4120, a heparan sulfate mimetic, a possible long-term active agent for healing burn skin (RGTA OTR4120, a topical sulfate mimetic, is a porous active to skin burn skin), Garcia-Filipee S, Barbier-Chassefierce V, Alexaks C, Huet E, Ledoux D, Kerros ME, Petit E, Barritault D, Caruelle JP, Kern P biomedical materials research part A (J Biomed Mater Res. A) 2007 for 1 year; 80(1) 75-8), promoting skin healing and treating pain (patent document EP1677807[9 ]).

These activities may be due in particular to the ability of these compounds to inhibit certain glycanases, such as heparanase, chondroitinase and hyaluronidase (Heparin-like synthetic polymers, named RGTA, mimic the biological effects of Heparin in vitro. round V, Medahi-Pelle A, Miao HQ, Vlodavsky I, Caruelle JP, Barritault D.J.Biol.Res.A.2006, 15 days; 78(4):792-7[10 (10) RGTAs ], a Heparin-like synthetic polymer, nano RGTAs, a mimic the biological effects of Heparin in vitro],EP1677807[9]Patent documents US06689741, US2014301972a1[4]]) The inhibition of elastase (FGF protection and inhibition of human neutrophil elastase by carboxymethyl benzylamide sulfonic acid dextran derivatives) (FGF protection and inhibition of human neutrophil elastase) — Meddahi a, Lemdjabar H, caroelle JP, Barritault D, Hornebeck w. (journal of biological macromolecules, 1996, 2 months); 18(1-2):141-5[11]Collagenase, plasmin (Human plasmin is inhibited by chemically modified dextrans) enzyme activity of Human plasmin (Ledoux D, copy-Garcia D, Escatin Q, Sago MA, Cao Y, Barritault D, Courtois J, Hornebeck W, Carue JP.. J. Biol Chem. 9/22.2000; 275(38):29383-90[12 (12) by 12)]) Andactivators of plasminogen or calpain (Heparan sulfate mimetics regulate calpain activity during rat Soleus regeneration.) Zimowska M, Szczepankowska D, Streminska W, copy D, Tournaire MC, Gautron J, Barritaut D, Moracczewski J, Martelly I. J. Cell physiology (J Cell physiology) 2001.8 months; 188(2):178-87[13 ] enzyme activity]) To provide protection in the region of the site (the site described in the literature as the heparin sulfate binding site or "heparin/heparin binding site") that binds to matrix proteins (growth and cell communication factors, i.e., VEGF and TGF β) ((ii))Or a rejuvenating agent that mimics heparan sulfate in rejuvenating medicine: from concept to cure of patients: (or ReGeneraTing Agents mimic heparan sulfate in regenerative medicine:from concept to curing patients).Barritault D,Gilbert-Sirieix M,Rice KL,F, Papy-Garcia D, Baudouin C, Desgranges P, Zakine G, Saffar JL, van Neck J., (Glycoconj J.) J.2017, 6 months; 34(3) 325-338, doi 10.1007/s10719-016 and 9744-5[ 14-])。

However, RGTA is used specifically during treatment of significant lesions and is often an expensive compound that cannot be used in the usual way, specifically in cosmetics.

There is therefore a real need to find new compounds, new compositions or treatments that make it possible to treat tissue ageing, in particular skin ageing, and/or to increase the therapeutic effect of the known compositions, while also reducing their cost.

Thus, in the prior art, there is a real need to find a compound and/or composition that enables the action and/or the significant effect on mechanisms involving age-related anatomical, histological and/or functional changes of tissues, in particular of the skin, while also having reduced costs.

Disclosure of Invention

The present invention aims in particular to meet these needs by providing a pharmaceutical composition, preferably a cosmetic or dermatological composition, comprising:

-biocompatible polymers of the general formula (I)

AaXxYy(I)

Wherein:

a represents a monomer, and A represents a monomer,

x represents-R₁COOR₂or-R₉(C＝O)R₁₀The radical(s) is (are),

y represents an O-sulfonate group or an N-sulfonate group corresponding to one of the following formulae: -R₃OSO₃R₄、-R₅NSO₃R₆、R₇SO₃R₈

Wherein:

R₁、R₃、R₅and R₉Independently represents an optionally branched and/or unsaturated aliphatic hydrocarbon chain optionally containing one or more aromatic rings, in addition to benzylamine and benzylaminosulfonate, R₂、R₄、R₆And R₈Independently represents a hydrogen atom or a cation,

R₇and R₁₀Independently represents a bond, an optionally branched and/or unsaturated aliphatic hydrocarbon chain,

"a" represents the number of monomers,

"X" represents the substitution rate of the group X for the monomer A,

"Y" represents the substitution rate of the group Y for the monomer A; and

-hyaluronic acid.

Advantageously, the inventors have surprisingly demonstrated that the association of a biocompatible polymer of general formula (I) as defined above (also referred to as RGTA in the present document) and hyaluronic acid makes it possible to treat and/or prevent the aging of biological tissues in a synergistic manner.

In particular, the inventors have demonstrated that the composition according to the invention advantageously allows preventing, reducing, eliminating or limiting the effects of age on the appearance of the skin, whether ageing is chronobiological or accelerated, for example due to external aggressions, for example due to radiation, such as UVA, UVA and/or ionizing rays.

The inventors have also surprisingly demonstrated that the effect achieved is visible and durable. In particular, the inventors have demonstrated that the composition according to the invention advantageously allows a visible and lasting reduction of signs and signs of aging, such as the reduction of fine lines and wrinkles, thus advantageously making it possible to improve the appearance of the skin, which may advantageously appear younger or have a more beautiful skin, such as a brighter skin, a more flexible, firmer and also firmer skin.

In particular, the inventors have demonstrated that the composition according to the invention advantageously makes it possible to protect tissues, such as the skin and/or mucous membranes, from external aggressions, for example due to exposure to radiation, such as UVA, UVA and/or ionizing radiation, cold, etc. In particular, the inventors have demonstrated that the composition according to the invention advantageously makes it possible to prevent and/or protect tissues such as the skin and/or mucous membranes from the effects of dryness. For example, the inventors have demonstrated that the compositions according to the invention advantageously synergistically exhibit a protective and/or hydrating effect on the mucosa and advantageously make it possible to reduce the effects associated with tissue desiccation.

The inventors have also demonstrated that the composition according to the invention advantageously makes it possible to promote the movement of joints and tendons, in particular by improving the properties of the tissues, such as hydration, flexibility, etc., in particular by improving the characteristics of the intervertebral discs and promoting the functional recovery of the tissues in a general way.

Furthermore, the inventors have demonstrated that the combination of a biocompatible polymer of general formula (I) according to the present invention and hyaluronic acid may be used/applied to any biological tissue, e.g. by topical application, e.g. through the skin and/or to the surface of the biological tissue. Furthermore, the inventors have demonstrated that the combination of a biocompatible polymer of general formula (I) according to the invention and hyaluronic acid can also be used/applied by injection.

The inventors have also surprisingly and unexpectedly demonstrated that the combination of a biocompatible polymer of general formula (I) according to the invention with hyaluronic acid shows a strong synergistic effect observed in the functional recovery of tissues and their recovery from scars.

Furthermore, the inventors have surprisingly and unexpectedly demonstrated that the combination of a biocompatible polymer of general formula (I) according to the invention with hyaluronic acid has a synergistic effect in scar treatment, such as scar treatment and scar aesthetic treatment.

Furthermore, the inventors have surprisingly demonstrated that the combination of a biocompatible polymer of general formula (I) according to the invention with hyaluronic acid has a lasting effect over time and in particular makes it possible to prolong the duration of the combined action by slowing down the elimination and moreover advantageously allows to restore both aspects of the synthesis and/or the production of biological elements, such as proteins constituting the extracellular matrix, the production of which decreases and/or changes with, for example, the ageing of biological tissues.

In the present document, "tissue" means any biological tissue of a mammal known to the person skilled in the art. The tissue may be, for example, connective, muscle, nerve, bone, cartilage, and/or epithelial tissue. For example, the tissue may be any biological tissue of any organ or organelle of a mammal known to those of skill in the art. The tissue may be, for example, digestive tract tissue, gastrointestinal tract tissue, food and excretory digestive system tissue, reproductive tract tissue, reproductive system tissue, visual, olfactory or auditory system tissue, sensory system tissue, circulatory system and/or cardiovascular system tissue, respiratory system tissue, muscular system tissue, motor system tissue. The tissue may be, for example, stomach tissue, cheek tissue, cornea, tympanic membrane tissue, cochlear tissue, skin tissue, bone tissue, cartilage tissue, tendon tissue, nerve tissue, bone marrow, nerve fibers, retina, artery and/or blood vessels, tissue of the renal or urodigestive system and/or any biological tissue allowing the passage of biological fluids, such as any biological tissue known to a person skilled in the art allowing the passage of biological fluids, such as schlemm's canal or the lymphatic system.

In the present document, "scar" means any tissue response to an insult of any type, duration or intensity, which results in inflammation and the formation of scar tissue that is different from the original tissue. For example, a "scar" may be the formation of any scar tissue known to those skilled in the art that is distinct from the original tissue. A "scar" may be, for example, scar tissue that is different from the original tissue, in which marks and/or fibrosis are formed that differ from aspects and characteristics of the original tissue, for example, in shape, flexibility, adhesiveness, and/or thickness.

In the present document, monomer means, for example, a monomer selected from the group comprising: a sugar, an ester, an alcohol, an amino acid, or a nucleotide.

In the present document, the monomers A which constitute the essential elements of the polymers of the formula I may be identical or different.

In the present document, monomer a may independently be a monomer of the formula:

wherein R is₉And R₁₀Independently represents an oxygen atom, an optionally branched and/or unsaturated aliphatic hydrocarbon chain, a heteroaryl group independently comprising one or more oxygen atoms and/or nitrogen atoms, an aldehyde function, a carboxylic acid group, a diol, a substituted diol, a compound of formula-R₁₁-(X)_n-R₁₂Wherein R is₁₁Represents optionally branched and/or unsaturated C₁To C₄An aliphatic carbon chain, X represents a heteroatom selected from oxygen and nitrogen, n is an integer between 1 and 4, and R₁₂Is a hydrogen atom, an optionally branched and/or unsaturated aliphatic hydrocarbon chain, independently comprising one or more oxygen atoms and/orNitrogen, aldehyde functional groups, carboxylic acid groups, glycols, substituted glycols.

In the present document, the association of the monomers may be such as to form a polymeric backbone, for example of the polyester, polyol or polysaccharide type, of the nucleic acid or of the protein type.

In the present document, the polyester may be, for example, a biosynthetic or chemically synthesized copolymer, such as an aliphatic polyester or a polyester of natural origin, such as a polyhydroxyalkanoate (polyhydroxyalconaote).

In the present document, the polysaccharides and derivatives thereof may be of bacterial, animal, fungal and/or plant origin. The polysaccharides and derivatives thereof may for example be single chain polysaccharides such as polydextrose, e.g. dextran, cellulose, beta-glucan or other monomers comprising more complex units, e.g. xanthan gum, e.g. glucose, mannose and glucuronic acid or indeed glucuronic acid esters (glucoluronane) and sugar-containing glucuronic acid esters (glucoglucuronane).

In the present document, the polysaccharides of plant origin may be single-chain, such as cellulose (glucose), pectin (galacturonic acid), fucoidan, starch or more complex, such as alginates (galacturonic acid and mannuronic acid).

In the present document, the polysaccharide of fungal origin may be, for example, scleroglucan (steroglucan).

In the present document, the polysaccharide of animal origin may be, for example, chitin or chitosan (glucosamine).

In the present document, the monomers A which constitute the essential elements of the polymers of the formula I may advantageously be identical.

In the present document, the monomer A which constitutes the basic element of the polymer of the formula I may advantageously be glucose.

The amount of monomer a defined by "a" in formula (I) may be such that the mass of the polymer of formula (I) is approximately between 2000 and 6000 daltons, for example corresponding to at least 10 glucose monomers. For example, the mass of the polymer of formula (I) may be approximately between 3000 daltons and 6000 daltons, for example corresponding to 12 to 20 glucose monomers.

The amount of monomer a defined by "a" in formula (I) may also be such that the mass of the polymer of formula (I) is less than about 2,500,000 daltons (corresponding to 7000 glucose monomers). Advantageously, the mass of the polymer of formula (I) may be between 3000 daltons and 250,000 daltons, such as 3000 daltons to 6000 daltons, or such as 20,000 daltons to 250,000 daltons, or such as 75,000 daltons to 150,000 daltons.

In the present document, in the radical-R which represents X₁COOR₂In, R₁Can be C₁To C₆Alkyl, such as methyl, ethyl, butyl, propyl, pentyl, preferably methyl, and R₂Can be a bond, C₁To C₆Alkyl radicals, e.g. methyl, ethyl, butyl, propyl, pentyl, R₂₁R₂₂Group, wherein R₂₁Is an anion, and R₂₂Is a cation selected from alkali metal groups.

The group X is preferably of the formula-R₁COOR₂Wherein R is₁is-CH₂-methyl, and R₂Is R₂₁R₂₂Group, wherein R₂₁Is an anion, and R₂₂Is a cation selected from alkali metal groups, preferably the group X is of the formula-CH₂-COO-or carboxymethyl groups.

In the present document, in the radical-R which represents X₉(C＝O)R₁₀In, R₉Can be C₁To C₆Alkyl, such as methyl, ethyl, butyl, propyl, pentyl, preferably methyl, and R₁₀Can be a bond, C₁To C₆Alkyl radicals, such as the methyl, ethyl, butyl, propyl, pentyl, hexyl radical.

The substitution rate of the group X defined by "X" in the general formula (I) for all monomers a may be 10% to 150%, 40% to 80%, and preferably about 50% or 60%.

In the present document, in the radical corresponding to one of the formulae, -R₃OSO₃R₄、-R₅NSO₃R₆、-R₇SO₃R₈And in the representative Y, R₃Can be a bond, C₁To C₆Alkyl, e.g. methyl, ethyl, butyl, propyl, pentyl, preferably methyl, R₅Can be a bond, C₁To C₆Alkyl, e.g. methyl, ethyl, butyl, propyl, pentyl, preferably methyl, R₇Can be a bond, C₁To C₆Alkyl, e.g. methyl, ethyl, butyl, propyl, pentyl, preferably methyl, R₄、R₆And R₈May independently be a hydrogen atom or a cation M⁺E.g. M⁺May be an alkali metal.

The radical Y is preferably of the formula-R₇SO₃R₈Wherein R is₇Is a bond, and R₈Is an alkali metal selected from the group comprising: lithium, sodium, potassium, rubidium, and cesium. The radical Y is preferably-SO₃ ^-、-SO₃ ^-、Na⁺A group.

The substitution rate of the group Y defined by "Y" in the general formula (I) for all monomers a may be 10% to 170%, 30% to 150%, 55% to 160%, 55% to 85%, 120% to 160%, and preferably about 70%, 140%, or 150%.

In the present document, in the definition of the above-mentioned substitution rate, a substitution rate "X" of 100% means that each monomer A of the polymer of the invention statistically contains one group X. Likewise, a substitution rate "Y" of 100% means that each monomer of the polymer of the invention statistically contains one group Y. Substitution rates above 100% indicate that each monomer statistically has more than one group of the type under consideration; vice versa, a substitution rate of less than 100% means that each monomer has statistically less than one group of the type considered.

The polymer may also include a chemical functional group, denoted as Z, that is different from X and Y.

In the present document, the groups Z may be identical or different and may be independently selected from the group comprising: amino acids, fatty alcohols, ceramides or derivatives thereof, or addressing nucleotide sequences.

The groups Z may also represent the same or different active agents. These active agents may be, for example, therapeutic agents, diagnostic agents, anti-inflammatory agents, antibacterial agents, antibiotics, growth factors, enzymes, antioxidant compounds, polyphenols, tannins, anthocyanins, lycopene, terpenes, and resveratrol.

In the present document, the group Z may advantageously be a saturated or unsaturated fatty acid. For example, the group Z may be a fatty acid selected from the group comprising: acetic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, hexacosanoic acid, myristoleic acid, palmitoleic acid, hexadecenoic acid (sapienic acid), oleic acid, elaidic acid, trans-octadecenoic acid, linoleic acid, linolenic acid, alpha-linoleic acid, gamma-linoleic acid, dihomo-gamma-linoleic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, or docosahexaenoic acid. The fatty acid is preferably acetic acid.

In the present document, the group Z may advantageously be an amino acid of the series L or D selected from the group comprising: alanine, asparagine, aromatic chains, such as tyrosine, phenylalanine, tryptophan, thyroxine or histidine. The amino acid is preferably phenylalanine.

In the present document, the group Z may be an antioxidant, such as vitamin A, C, E, B9, B6, glutathione, selenium, a polyphenol, such as a catechin, such as green tea, a flavonoid, a tannin, an anthocyanin, such as red fruit, lycopene, a terpene and resveratrol.

In the present document, the group Z may be an anti-ageing compound, for example a retinoid.

The group Z may advantageously provide additional biological or physicochemical properties to the polymer. For example, the group Z may increase the solubility or lipophilicity of the polymer, which allows, for example, improved diffusion or tissue penetration.

The group Z may advantageously provide additional biological or physicochemical properties to the polymer. Thus, the polymer of the invention may advantageously transport said compounds, e.g. when the group Z is selected from antioxidant compounds, anti-aging compounds, and thus provide additional and/or complementary biological effects.

The polymer in which Z is present corresponds to formula II below:

Aa Xx Yy Zz (II)

wherein A, X, Y, a, X, Y are as defined above and Z represents the substitution rate of the group Z.

In the present document, the substitution rate of the Z group represented by "Z" may be 1% to 50%, 10% to 25%, preferably 15%, 20% or 25%.

X, Y and the Z groups can be bound independently to monomer A and/or to each other. When at least one of groups X, Y and Z is independently bound to a group X, Y and Z different from the first group, one of the groups X, Y or Z is bound to monomer a.

Thus, the group Z may be directly bound to the monomer A by covalent bonding or bound to the groups X and/or Y by covalent bonding.

In the present document, the group Z may also be conjugated to the polymer of formula AaXxYy via a bond other than a covalent bond, for example via an ionic bond, for example via ionic interactions, a hydrophilic bond or a hydrophobic bond. The polymers of the invention can thus form a vectorised system of Z.

In the present document, the polymer may for example be an RGTA selected from the group comprising: compounds OTR4120, OTR41201, OTR41202, OTR41203, OTR41205, OTR41210, OTR41301, OTR41302, OTR41303, OTR41305, OTR41310, OTR 3131.

In the present document, the polymer may for example be an RGTA selected from the group comprising the following features mentioned in table 1 below: compounds OTR41201, OTR41202, OTR41203, OTR41205, OTR41210, OTR4120, OTR4122, OTR4125, OTR41301, OTR41302, OTR41303, OTR41305, OTR41310, OTR3131, OTR4132, OTR4135, OTR 415.

Table 1: aa Xx Yy and Aa Xx Yy Zz families of polymers, wherein a is glucose (molecular weight 180D), X is carboxymethyl (molecular weight 58D) Y: SO3^-(molecular weight: 80D), Z is acetate (molecular weight: 43D) or phenylalanine (molecular weight: 165D).

In the present document, the concentration of the composition may be from 0.1 μ g/mL to 100 μ g/mL by weight of the biocompatible polymer, relative to the volume of the composition. For example, a preferred concentration of the composition may be 1 μ g/mL to 10 μ g/mL by weight of the biocompatible polymer, relative to the total volume of the composition.

In the present document, the composition may be formulated and/or adjusted according to its application. For example, for topical administration, the composition can comprise 0.1 μ g/mL to 100 μ g/mL by weight of the biocompatible polymer, relative to the total volume of the composition.

For example, for parenteral administration, the composition may be administered to deliver a dose of biocompatible polymer of between 0.1mg and 5mg per kilogram of body weight.

The molecular weight of the biocompatible polymer present in the composition may be advantageously selected according to the route of administration of the composition and the target, e.g., epidermis, dermal mucosa, cornea, tympanic membrane, organ, intra-articular fluid, intraocular fluid.

For example, for topical or oral administration, the molecular weight may be between 3000 daltons and 6000 daltons to facilitate passage of the basement membrane. For example, for administration by intradermal or subcutaneous or intrathecal injection, or injection into a muscle or organ or intra-articular space, the molecular weight may be from 6000 daltons to 2,500,000 daltons, preferably from 20,000 daltons to 250,000 daltons, and for example from 75,000 daltons to 150,000 daltons.

Advantageously, when the biocompatible polymer has a molecular weight between 3000 and 6000 daltons, in the case of topical application, for example on epithelial cells, such as mucous membranes or skin, the biocompatible polymer may advantageously allow the basement membrane to pass through, advantageously achieving improved application, and may increase the effect over a greater distance.

Advantageously, the biocompatible polymer advantageously achieves increased usability and increased longevity regardless of tissue location when the biocompatible polymer has a molecular weight between 3000 daltons and 2,500,000 daltons.

In the present document, "hyaluronic acid" means any hyaluronic acid known to a person skilled in the art, such as the non-sulphated linear glycosaminoglycans constituted by D-glucuronic acid and N-acetyl-D-glucosamine of repeating units. The "hyaluronic acid" may for example be Hyaluronic Acid (HA), cross-linked hyaluronic acid, in its acid form or in its salt (hyaluronate) form. HA is a non-sulfated linear glycosaminoglycan composed of repeating units of D-glucuronic acid and N-acetyl-D-glucosamine (Tammi R., Agren UM., Tuhkanen AL., Tammi M. hyaluronic acid metabolism in skin (Hyalcuronan metabolism in skin). advances in Histochemistry and Cytochemistry 29(2):1-81,1994[15 ]). HA may for example be hyaluronic acid with an average molecular weight fraction of 5000 to 3,000,000 dalton, preferably between 50,000 and 2,000,000 dalton. In the present document, hyaluronic acid may be obtained by any method known to a person skilled in the art. These methods can be exemplified in the review of hyaluronic acid fragments: a method described in the information-rich system (Hyaluronan fragments: an information-rich system) (R.Stern et al, J.European Cell Biology 58(2006)699-715[16 ]). HA may also be a natural or modified hyaluronic acid, which is commercially available regardless of its name and/or molecular weight, for example a commercially available hyaluronic acid selected from: a Hyactive CPN; cristalheal; nutra HA; oligo HA; d, Factor; hyaludermjuvelift; restylane; revitacare, this list is not exhaustive. HAHIA may be hyaluronic acid sold by Condit Proro (Contipro) (https:// www.contipro.com/portal/manual-of-anti-agening-cosmetic-raw-materials/Hyactive) and/or by Qihuadan corporation (Givaudan) (https:// www.givaudan.com/fragments/active-beans/products/crystalline% C2% AE-range).

In the present document, the concentration of the composition may be 0.1 to 5 wt.% hyaluronic acid, relative to the total weight of the composition. For example, the concentration of the composition may be 0.5 wt.% to 2.5 wt.% hyaluronic acid, relative to the total weight of the composition.

In the present document, the composition may be formulated and/or adjusted according to its application. For example, for topical administration, the composition may comprise 0.5 to 2.5 wt.% hyaluronic acid, relative to the total weight of the composition.

For example, for parenteral administration, e.g., intra-articular administration, e.g., in the synovial fluid of the knee or in the synovial fluid of the trapezium-metacarpal or metacarpophalangeal joints, e.g., for carpal joint disease or e.g., for intra-tendinous such as tendonitis, the composition may be administered to deliver a dose of 1mg to 20mg of hyaluronic acid per mL of composition. For example, for parenteral administration, the concentration of the composition can be 0.1mg/mL to 20mg/mL hyaluronic acid.

The molecular weight of the biocompatible polymer present in the composition may be advantageously selected according to the route of administration of the composition.

In the present document, "pharmaceutical composition" means any form of pharmaceutical composition known to the person skilled in the art. In the present document, the pharmaceutical composition may for example be a composition for topical administration, such as an injectable solution for local or systemic injection, for example in physiological serum injectable in glucose solutions, in the presence of excipients such as dextran, for example at concentrations known to those skilled in the art, for example from micrograms to several milligrams per mL.

The pharmaceutical composition may for example be a medicament intended for oral administration, selected from the group comprising: liquid formulations, oral effervescent dosage forms, oral powders, multiparticulate systems, orodispersible galenic forms.

For example, when the pharmaceutical composition is for oral administration, the pharmaceutical composition may be in the form of a liquid formulation selected from the group comprising: solutions, syrups, suspensions, emulsions. When the pharmaceutical composition is in the form of an oral effervescent, the pharmaceutical composition may be in a form selected from the group consisting of tablets, granules, powders. When the pharmaceutical composition is in the form of an oral powder or multiparticulate system, the pharmaceutical composition may be in a form selected from the group comprising: pellets, granules, mini-tablets and microgranules. When the pharmaceutical composition is in the form of an orodispersible dosage form, the pharmaceutical composition may be in a form selected from the group comprising: orodispersible tablets, freeze-dried wafers, films, chewable tablets, capsules or medical chewing gums.

According to the present invention, the pharmaceutical composition may be a pharmaceutical composition for oral administration, e.g. by oral and/or sublingual administration, e.g. selected from the group comprising: buccal or sublingual tablets, dental pastes, dental buccal adhesive dressings, lozenges, drops, nebulized solutions.

According to the present invention, the pharmaceutical composition may be a pharmaceutical composition for intraurethral administration. Advantageously, when the pharmaceutical composition is suitable for intraurethral administration, the pharmaceutical composition may reach the epithelial cells of the bladder after administration.

According to the invention, the pharmaceutical composition may be, for example, a dermatological or cosmetic composition for topical application and/or application.

The dermatological or cosmetic composition according to the invention may comprise one or more dermatologically and/or cosmetically acceptable carriers. In the present document, "dermatologically and/or cosmetically acceptable carrier" means any cosmetic carrier known to the person skilled in the art; the dermatologically and/or cosmetically acceptable carrier may be, for example, any Cosmetic carrier that may be cited in the INCI dictionary (International Nomenclature of Cosmetic Ingredients) published by the PCPC (Personal Care Products Council).

The dermatological or cosmetic composition according to the invention may comprise one or more adjuvants known to the person skilled in the art. The dermatological or cosmetic composition may, for example, be one or more adjuvants selected from the group consisting of: ester-type agents, hydrating agents, emollients, mineral thickeners, organic thickeners, associative or otherwise water-and fat-soluble organic solar filters, mineral solar filters, silicon compounds, fragrances, preservatives, ceramides and pseudoceramides, vitamins and provitamins, proteins, chelating agents, alkalizing agents, acidifying agents, reducing agents, oxidizing agents, mineral fillers, adjuvants for colorants or any other adjuvant that may be cited in the INCI (international nomenclature for cosmetics) dictionary published by the PCPC (personal care products association).

The cosmetic composition according to the invention may be, for example, in any form known to the person skilled in the art. For example, the cosmetic composition may be an oil-in-water emulsion, a water-in-oil emulsion, a water-in-silicon emulsion, a multiple emulsion, a microemulsion, a nanoemulsion, a solid emulsion, an aqueous or hydroalcoholic gel, a cream, a gel, a milk, a lotion, a cream, an oil, a balm, an ointment, a mask, a compact, an impregnated carrier, such as a transdermal patch, an impregnated dressing, an aqueous lotion, a spray or hydroalcoholic and/or wax, a shampoo, a hair conditioner, a hair mask, a serum, or a lotion. The cosmetic composition according to the invention may preferably be in a form selected from creams, gels, ointments, oils.

The cosmetic or dermatological composition of the invention can be obtained by any suitable method for preparing a cosmetic and/or dermatological composition known to the person skilled in the art.

According to the invention, the pharmaceutical composition may be a pharmaceutical composition for respiratory or nasal administration, e.g. in the form of an aerosol.

According to the invention, the composition may be a composition for nasal or respiratory tract use, for example selected from the group comprising: nasal drops, nasal sprays, nasal powders, aerosols, e.g. compressed gas nasal aerosols and/or sprays or nebulisers.

Advantageously, when the pharmaceutical composition is suitable for nasal administration or for passage through the respiratory pathway, the pharmaceutical composition may advantageously be for passage through the broncholung.

According to the present invention, the composition of the present invention may be a composition for parenteral, e.g. subcutaneous, intramuscular, intravenous, intrathecal administration.

According to the present invention, the composition may be a composition for ocular administration, for example selected from the group comprising drops, gels, creams. The composition may be, for example, an eye wash, for example, for treating the cornea by applying the composition to the surface of the eye, for example in the treatment of the cartesian's membrane, by transcorneal injection, or indeed for treating glaucoma, to reduce fibrosis of Schlemm's canal (Schlemm's canal), for example, by injection into the aqueous or vitreous humor of the eye, for example, by topical application to the cornea.

Advantageously, when the composition is used for topical application on the cornea, said composition may advantageously be used in the transcorneal region, advantageously if the composition comprises a low molecular weight polymer, for example between 2000 daltons and 6000 daltons.

Depending on the galenic formulation used, the composition of the invention may also comprise at least one other active ingredient, in particular another therapeutically active ingredient, for example for simultaneous or separate use or for use distributed over time. The other ingredients may for example be active ingredients for the treatment of opportunistic infections, or vitamins or analgesics etc.

In the present document, the administration of the biocompatible polymer and the hyaluronic acid may be simultaneous, sequential or concurrent.

According to the invention, the administration may be performed at least one of topically, orally, by respiratory route or by injection. The two administrations may be carried out in the same or different ways. For example, the application of the biocompatible polymer and hyaluronic acid may be performed by topical application. Administration may also depend on the area and/or biological tissue to be treated.

According to the invention, the composition may, for example, be applied only once.

According to the invention, the composition may furthermore be administered, for example, daily, every other day, and weekly or less frequently. For example, the composition may be administered once a day, twice a day, or less frequently, e.g., once every other day or once a week.

Depending on the invention and the mode of administration, the composition may be applied in the form of a cream, for example daily, every other day and weekly or less frequently. For example, the composition may be administered once a day, twice a day, or less frequently.

According to the invention, the composition may be administered, for example, over a period of 1 day to 3 months, for example over a period of 2 months. For example, the composition may be administered over a period of 3 or 6 months, e.g., at a daily administration frequency.

For example, when the composition is in an injectable form, the composition may be administered at an administration frequency of every 3 months or 6 months or less.

The inventors have surprisingly demonstrated that the combination of a biocompatible polymer of formula AaXxYy or aaxxyyyzz with natural or modified hyaluronic acid advantageously and surprisingly makes it possible to achieve a synergistic effect in therapy. In particular, the inventors have demonstrated that the effects obtained are both synergistic effects extending beyond the individual effects of each of the compounds and also advantageously increasing the duration of these effects.

Furthermore, the inventors have surprisingly shown that the increase in duration of effect can be further increased, for example by using multiple administrations, for example by the same or different administration routes and/or specific administration dosimetry. For example, after administration of the composition according to the invention by e.g. subcutaneous, intramuscular injection, application through the skin, e.g. by topical application, of the composition according to the invention may be carried out.

In the present document, the compositions according to the invention can be applied simultaneously, consecutively or in parallel by different routes.

According to the present invention, at least one of the administrations may be performed by topical, oral or by injection. The two administrations may be carried out in the same or different ways. For example, administration of the composition can be by injection followed by topical application of the composition. Administration may also depend on the area and/or biological tissue to be treated.

Advantageously, when the application of the composition can be carried out by injection, followed by the topical application of the composition, the composition for topical application can be in a form chosen from a cream, a gel or a serum.

Advantageously, the inventors have surprisingly demonstrated that the topical application of a composition in a form selected from a cream, a gel or a serum surprisingly makes it possible to further extend the biological effect produced by the first application.

The invention also relates to a cosmetic or dermatological composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz and natural or modified hyaluronic acid for use in the non-therapeutic cosmetic treatment of skin ageing, wrinkles and/or wrinkles, in order to protect the scalp and for the regeneration of capillaries.

The biocompatible polymer is as defined above.

Hyaluronic acid is as defined above.

According to the invention, the patient may be any mammal. The patient may for example be an animal or a human.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above.

According to the invention, the mode and/or route of administration of the hyaluronic acid may be as defined above, preferably by injection into the biological tissue.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the invention, the frequency of administration of hyaluronic acid may be as defined above.

The invention also relates to a cosmetic or dermatological composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz and natural or modified hyaluronic acid for use in the non-therapeutic cosmetic prevention and/or treatment of hair loss and/or baldness.

The biocompatible polymer is as defined above.

Hyaluronic acid is as defined above.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above.

According to the invention, the mode and/or route of administration of the hyaluronic acid may be as defined above, preferably by injection into the biological tissue.

The cosmetic or dermatological composition comprising a biocompatible polymer of formula AaXxYy or aaxxyyyzz and hyaluronic acid according to the invention may be a composition for topical and/or capillary application, such as a cream.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the invention, the frequency of administration of hyaluronic acid may be as defined above.

The invention also relates to a cosmetic or dermatological anti-aging composition and/or a composition for protecting the skin from external aggressions and/or for treating and/or preventing skin aging, comprising a biocompatible polymer of formula AaXxYy or AaXyZz and hyaluronic acid.

The biocompatible polymer is as defined above.

Hyaluronic acid is as defined above.

According to the invention, the patient may be any mammal. The patient may for example be an animal or a human.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above.

According to the invention, the mode and/or route of administration of the hyaluronic acid may be as defined above, preferably by injection into the biological tissue.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the invention, the frequency of administration of hyaluronic acid may be as defined above.

The invention also relates to a cosmetic treatment method comprising applying to the skin a cosmetic composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz and hyaluronic acid.

The biocompatible polymer is as defined above.

Hyaluronic acid is as defined above.

According to the invention, the patient may be any mammal. The patient may for example be an animal or a human.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above.

According to the invention, the mode and/or route of administration of the hyaluronic acid may be as defined above, preferably by injection into the biological tissue.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the invention, the frequency of administration of hyaluronic acid may be as defined above.

In the present document, cosmetic treatment means non-therapeutic cosmetic treatment.

According to the invention, the non-therapeutic cosmetic treatment may be an anti-ageing cosmetic treatment, a cosmetic treatment for preventing skin ageing, a cosmetic treatment of skin ageing and/or a cosmetic treatment of mature skin.

Indeed, as mentioned above, the inventors of the present invention have surprisingly demonstrated that the composition according to the invention makes it possible to stimulate the hydration of tissues in a synergistic manner, advantageously over time and in particular in a manner correlated with the production of an improved tissue environment, thus surprisingly extending the effect of hyaluronic acid, while reducing the activity of the glycanase and stimulating the response of proximal cells, advantageously and surprisingly allowing the new synthesis of extracellular matrix components whose quality is improved while restoring the distribution and polarity of the matrix.

For such administration, for example, galenic forms as described above can be used. It can therefore be applied to the skin according to the galenic form used.

The application may be, for example, a simple application on the skin or a concomitant application with massaging the skin with the composition of the invention.

The application may be, for example, a continuous application of the composition according to the invention, said application comprising a first application of the composition according to the invention, for example by cutaneous injection, followed by a topical application of said composition according to the invention.

The composition is preferably applied using a sufficient amount of the composition, for example to ensure treatment of the entire surface of the skin to be treated. The application may for example be a conventional application, such as a cream on the skin. The application may also be, for example, an application to form a treatment mask.

The application may be, for example, daily, weekly, and bimonthly. The application may be, for example, once a day, twice a day, or less frequently.

The inventors have also surprisingly demonstrated that the composition according to the invention advantageously makes it possible to fill fine lines more effectively, while avoiding possible side effects compared to known products, such as collagen and/or botulinum toxin injections. Furthermore, the inventors have demonstrated that the composition according to the invention can be used as a filler, for example for filling fine lines, but also for injection in aesthetic treatments and/or as a filler, for example for hydration and expansion, for example in the area of male or female genital organs and/or sexual organs.

The invention therefore also relates to the use of a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid as a filler and/or filler, for example as a filler and/or filler of organs and/or biological tissues.

The invention therefore also relates to the cosmetic use as filler and/or filler of the skin, comprising a composition of a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid.

The inventors have also surprisingly demonstrated that the composition according to the invention advantageously makes it possible to improve the scarring of biological tissue lesions, in particular by promoting the hydration of the tissue and filling the lesion. In particular, the inventors have surprisingly demonstrated that the composition according to the invention advantageously makes it possible to promote cutaneous scarring and/or to improve the appearance of cutaneous lesions, such as scars.

The invention therefore also relates to the cosmetic use of a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for example to improve the appearance of skin lesions, such as scars.

The invention therefore also relates to the cosmetic use of a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid for the treatment of skin lesions.

The inventors have also surprisingly demonstrated that the composition according to the invention advantageously makes it possible to improve the scarring of biological tissue lesions, in particular by promoting the hydration of the tissue, preventing the formation of fibrosis and filling the lesions.

In particular, the inventors have demonstrated that the composition according to the invention advantageously makes it possible to increase the speed and physical quality of the scar tissue, in particular the mechanical properties of the scar tissue, the flexibility of the scar tissue and the hydration of the scar tissue.

Furthermore, the inventors have demonstrated that, in particular in the examples, the lesions that can be treated by the composition according to the invention can be any type of tissue lesion, regardless of its origin and any type of tissue or organ. In particular, from the following examples of effectively treating various pathologies, those skilled in the art will readily understand and be able to infer from this knowledge other tissue pathologies that can be treated by the present invention.

In the present document, "tissue lesion" means any lesion or lesion of any biological tissue of a mammal known to a person skilled in the art. This "tissue lesion" may be a lesion of, for example, connective tissue, muscle tissue, bone tissue, cartilage tissue and/or epithelial tissue. The "tissue lesion" may be, for example, any lesion of any organ or organelle of a mammal known to those skilled in the art. The "tissue pathology" may for example be damage to tissue of the digestive tract, tissue of the gastrointestinal tract, tissue of the alimentary and excretory digestive system, tissue of the reproductive tract, tissue of the reproductive system, tissue of the visual, olfactory or auditory system, tissue of the sensory system, tissue of the circulatory and/or cardiovascular system, tissue of the respiratory system, tissue of the muscular system, tissue of the motor system. Said "tissue lesion" may for example be a gastric tissue lesion, a cheek lesion, a corneal lesion, a tympanic lesion, a cochlear lesion, a skin lesion, such as a wound, a chronic wound, such as a diabetic wound, an ulcer wound, a decubitus ulcer, a skin burn, a necrotic wound, a venous lesion, an ischemic lesion, such as an ischemic necrosis, a lesion caused by a heart disease, such as a myocardial infarction, a bone lesion, such as a bone fracture, a bone defective fracture, a bone non-union fracture, a osteochondral lesion, a cartilage lesion, a tendon lesion, a surgical lesion, a lesion due to a surgical operation, a lesion caused by a medical treatment, such as a radiotherapy, a nerve tissue lesion, such as a brain lesion, a lesion, such as a tumor removal lesion, a bone marrow lesion, a nerve fiber lesion, such as a motor and/or sensory system lesion, a respiratory system lesion, such as a lung lesion, a circulatory system lesion, such as arterial and/or vascular lesions, digestive, hepatic, renal or urological lesions.

The invention also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXyYZz according to the invention and hyaluronic acid for use as a medicament.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating tissue pathologies.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating a tissue pathology selected from: eye disorders, vocal cord disorders, joint disorders, intervertebral disc disorders, tendinopathies and/or ligament disorders, retinopathies, e.g. retinal detachment, Behcet's disease: (disease) Induced lesions, superficial lesions, such as skin wounds, ulcers, such as ulcers of diabetic wounds, gastric ulcers.

The inventors have also demonstrated that the composition according to the invention advantageously makes it possible to become an accelerator/hydrating agent and/or a joint lubricant for joints after administration into the joints, advantageously makes it possible to prevent and/or treat joint inflammation, to prevent and/or treat arthritis and/or arthropathy.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating pathologies and/or pathologies of the locomotor system.

According to the present invention, by pathology and/or pathology of the locomotor system is meant any pathology and/or pathology known to the person skilled in the art capable of modifying and/or changing the function of the locomotor system. The pathology and/or condition may be, for example, a joint pathology, such as joint inflammation, arthropathy, arthritis. The pathology and/or condition may be, for example, a pathology in a tendon or ligament region, such as inflammation, stretching, flattening, lesions, breaking or tearing. The pathology and/or condition may be, for example, a pathology in the spinal column and/or disc region, such as displacement, flattening, compression, or compression associated with trauma, age, dehydration, or the like;

the inventors have also demonstrated that the composition according to the invention advantageously allows to fill and strengthen the sub-retinal environment, in particular in the case of retinal detachment, and advantageously protects the retinal microenvironment in dry ARMD and moist ARMD after administration into the eye, thus advantageously making it possible to prevent and/or treat retinopathies, such as retinal detachment and/or to treat age-related macular degeneration, dry age-related macular degeneration and wet age-related macular degeneration.

The inventors have also surprisingly demonstrated that the composition according to the invention advantageously makes it possible to improve tissue hydration.

Furthermore, the inventors have demonstrated that, in particular in the examples, the composition according to the invention makes it possible to treat and/or improve the hydration of all types of tissues or organs. In particular, from the following examples of effectively treating various tissues and organs, those skilled in the art will readily understand and can infer from this knowledge the tissues and organs capable of being treated by the present invention.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating tissue dryness.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating the dryness of a tissue, in particular selected from: drying of naturally moist mucous membranes, e.g. ocular, buccal, vaginal or nasal mucosa, tissue in contact with biological fluids like synovial fluid, cerebrospinal fluid, peritoneum, pericardial fluid, bone marrow, joint tissue, epithelium, e.g. drying of the bladder, drying of the lymphatic system, drying of the spinal cord.

Furthermore, the inventors have demonstrated that, in particular in the examples, the composition according to the invention makes it possible to treat and/or improve the hydration of tissue or organ mucus. In particular, from the following examples of effectively treating various tissues and organs, those skilled in the art will readily understand and can infer from this knowledge the tissues and organs capable of being treated by the present invention.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating dryness of mucous membranes, such as vaginal mucosa, oral mucosa.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating dry eyes.

The inventors have also surprisingly demonstrated that the composition according to the invention advantageously makes it possible to treat fibrosis of biological tissues; in particular, the inventors have demonstrated that the composition according to the invention surprisingly makes it possible to reduce fibrosis, in particular to synergistically reduce the synthesis ratio of collagen 3 and collagen 1(COL 3/COL1), the fibrosis being characterized in particular by an overexpression of COL3 relative to COL 1.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating fibrosis.

Furthermore, the inventors have demonstrated that, in particular in the examples, the fibrosis that can be treated by the composition according to the invention can be any type of fibrosis, regardless of its origin and of any type of tissue or organ. In particular, from the following examples of effectively treating various fibrosis, those skilled in the art will readily understand and be able to infer from this knowledge other fibrosis that can be treated by the present invention. These fibrosis may be, for example, fibrosis caused by ischemic lesions, such as muscle and/or cardiac ischemic lesions. The fibrosis may be, for example, in skeletal muscle ischemia or fragmentation, scar fibrosis in infarcted myocardial ischemia, fibrosis of tendon tissue or ligaments, fibrosis of bone tissue, e.g. bone callus, fibrosis of digestive tissue, e.g. in crohn's disease, fibrosis after radiotherapy, liver fibrosis, lung fibrosis, fibrosis due to Peyronie's disease, fibrosis after surgery, e.g. fibrosis leading to organ or tissue adhesion, e.g. fibrosis after gastrointestinal surgery, tendons, nerves, vascular surgery, natural fibrosis, e.g. fibrosis occurring during glaucoma, e.g. fibrosis of schlemm's canal, fibrosis occurring during e.g. Dupuytren's disease, fibrosis caused by carpal tunnel syndrome, and/or other tendon fibrosis.

According to the invention, hyaluronic acid is as defined above. Gamma ray

According to the invention, the biocompatible polymer of formula AaXxYy or AaXxYyZz is as defined above.

According to the invention, the pharmaceutical or dermatological composition is as defined above.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above.

The inventors have also surprisingly demonstrated that the composition according to the invention can be advantageously used for the treatment of epidermolysis bullosa. In particular, the inventors have surprisingly and unexpectedly demonstrated that a composition comprising a biocompatible polymer of formula AaXxYy or aaxxyyyzz and hyaluronic acid advantageously makes it possible to promote scarring of ulcers in children with epidermolysis bullosa.

The inventors have also surprisingly and unexpectedly demonstrated that the composition according to the invention advantageously makes it possible to promote the scarring of ulcers and to reduce the pain associated with these ulcers in a synergistic manner.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating epidermolysis bullosa.

According to the invention, hyaluronic acid is as defined above.

According to the invention, the biocompatible polymer of formula AaXxYy or AaXxYyZz is as defined above.

According to the invention, the pharmaceutical or dermatological composition is as defined above. The composition may advantageously be in a form suitable for spraying, for example using a spray.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above. The application may be, for example, a skin application by spraying, for example, using an atomizer comprising the composition.

The inventors have also surprisingly shown that the composition according to the invention can be advantageously used for the treatment of periodontal disease.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for the prevention and/or treatment of periodontal disease.

In the present document periodontal disease means any periodontal disease known to the person skilled in the art. The periodontal disease may be gingivitis or periodontitis, for example.

The inventors have also surprisingly shown that the composition according to the invention can be advantageously used for the treatment of diseases of the oral mucosa.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating pathologies of the oral mucosa.

In the present document, the pathology of the oral mucosa means any pathology of the oral mucosa known to a person skilled in the art. For example, the oral mucosa may be a canker sore, gingivitis, mucositis.

The inventors have also surprisingly shown that the composition according to the invention can be advantageously used for treating skin burns of any origin. These skin burns may be, for example, thermal burns, radiation burns, skin burns due to exposure to UV radiation, skin burns due to exposure to ionizing radiation, such as exposure to X-rays or gamma rays.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating skin burns.

According to the invention, hyaluronic acid is as defined above.

According to the invention, the biocompatible polymer of formula AaXxYy or AaXxYyZz is as defined above. The molecular weight of the biocompatible polymer of formula AaXxYy or AaXxYyZz may advantageously be between 3000 daltons and 150,000 daltons.

According to the invention, the pharmaceutical or dermatological composition is as defined above. The composition may advantageously be in a form suitable for spraying, for example using a spray and/or gel. The composition may advantageously be in a form suitable for spraying, e.g. a spray or a gel, and does not contain fatty acids.

Advantageously, when the composition is in a form suitable for spraying, for example a spray and/or a gel, and does not contain fatty acids, it advantageously makes it possible to treat burns, while avoiding the presence of fatty acid residues, thus preventing any possible adverse effects.

The inventors have also surprisingly demonstrated that the composition according to the invention can be advantageously used for the treatment of degenerative diseases.

The invention therefore also relates to a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz according to the invention and hyaluronic acid, for use as a medicament for preventing and/or treating degenerative diseases.

In the present document, degenerative diseases mean any degenerative disease known to the person skilled in the art. These degenerative diseases may for example be sequelae, such as sequelae associated with vascular cerebrovascular accidents, neurodegenerative diseases, such as Alzheimer's disease, such as Parkinson's disease, retinal degeneration, degenerative diseases associated with tissue degradation, such as joint and/or muscle, muscle diseases, age-related degenerative diseases.

The inventors have advantageously demonstrated that a composition comprising a biocompatible polymer of formula AaXxYy or aaxxyyyzz and hyaluronic acid makes it possible to reproduce a better cellular microenvironment favorable to the functional survival and recovery of tissues, advantageously allowing to reduce and/or treat degenerative diseases.

The invention also relates to a composition for application as a medicament, comprising a biocompatible polymer of formula AaXxYy or AaXyYZz and hyaluronic acid.

According to the invention, hyaluronic acid is as defined above. According to the invention, the biocompatible polymer of formula AaXxYy or AaXxYyZz is as defined above.

The composition is as defined above.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above.

The present invention also relates to a method for treating a patient, the method comprising any sequence of the following steps:

i. administering at least one biocompatible polymer; and

administering a hyaluronic acid to the subject in need thereof,

wherein the administration is simultaneous, sequential or alternating.

The biocompatible polymer is as defined above.

Hyaluronic acid is as defined above.

According to the invention, the patient may be any mammal. The patient may for example be an animal or a human.

According to the present invention, the mode and/or route of administration of the biocompatible polymer may be as defined above.

According to the invention, the mode and/or route of administration of the hyaluronic acid may be as defined above, preferably by injection into the biological tissue.

According to the invention, the frequency of administration of the biocompatible polymer may be as defined above.

According to the invention, the frequency of administration of hyaluronic acid may be as defined above.

According to the invention, the administration of hyaluronic acid and biocompatible polymer may be simultaneous, for example in a single mixture or composition, or sequential.

According to the invention, in the case of successive administration of hyaluronic acid and biocompatible polymer, for example for each administration, the dosimetry may be the administration of hyaluronic acid followed by the administration of the biocompatible polymer. For example, hyaluronic acid may be administered between 1 minute and 48 hours prior to administration of the biocompatible polymer.

In other words, even if a composition is mentioned in the description of the invention, it is understood that each of the compounds of the composition may be administered simultaneously with the other compounds (e.g. in a single composition or in two compositions, each of these compositions comprising one or more of the above-mentioned components, the mode of administration of each compound or composition in the compound or composition may be the same or different) or independently of each other, e.g. continuously, e.g. independently of the biocompatible polymer and independently of the hyaluronic acid, said administrations being carried out simultaneously or sequentially or in an alternating manner to the same patient in the order as described above or in a different order. These different administrations may be carried out once or twice weekly, independently of one another or in a correlated pattern (composition or co-administration), by the same or different administration means (injection, ingestion, topical application, etc.) for one or more weeks, continuously or discontinuously.

The present invention thus advantageously provides a general and simple response to complex technical problems for which there is a real and continuing need in the art. In the following examples, which are specified in a non-limiting manner, all types of pathologies whatever their origin, as well as all types of tissues or organs, can be easily inferred by the person skilled in the art.

In particular, the inventors have demonstrated that the present invention can be generalized to all pathologies and/or pathologies, in particular due to the particular common feature of pathologies and/or pathologies, which is an alteration of the extracellular matrix.

The invention also relates to a method for preparing an ex vivo graft comprising impregnating the graft and/or the organ to be transplanted with a composition comprising a biocompatible polymer of formula AaXxYy or AaXyZz as defined above and hyaluronic acid.

The invention also relates to the use of a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz as defined above and hyaluronic acid for the ex vivo preparation of grafts and/or organs.

The biocompatible polymer is as defined above.

Hyaluronic acid is as defined above.

According to the invention, impregnation can be carried out by any method known to the person skilled in the art. The impregnation may for example be by infusion of a composition comprising a biocompatible polymer of formula AaXxYy or aaxxyyyzz as defined above and hyaluronic acid or by spraying a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz as defined above and hyaluronic acid into the organ and/or into the organ into a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz as defined above and hyaluronic acid.

The present invention also relates to the use of a composition comprising a biocompatible polymer of formula AaXxYy or AaXxYyZz as defined above and hyaluronic acid for the preparation of an implantable biomaterial in vitro and/or ex vivo.

For example, for implantable biomaterials, the biocompatible polymer may be added after preparation of the biomaterial, e.g., tissue or organ, e.g., by dipping. The biocompatible polymer may also be added, e.g. from the beginning during the preparation of the biomaterial, e.g. a biocompatible polymer of formula AaXxYy or AaXxYyZz as defined below and hyaluronic acid in successive layers, e.g. in a manner similar to 3D printing.

In the present document, "implantable biomaterial" means any implantable biomaterial known and/or commercially available to those skilled in the art. The implantable biomaterial may be, for example, a compatible implantable material, such as any type of compatible implantable material that is biodegradable, cross-linked, or otherwise preferably implantable. The implantable biomaterial may be an implantable biomaterial based on protein cross-linking, such as collagen, fibrin, polysaccharides, such as dextran, chitin, hyaluronic acid, alginate, cellulose and derivatives thereof, a biodegradable and biocompatible copolymer based on glycolic acid, lactic acid, malic acid, polymers, which may undergo liquid-gel transition, for example by polymerization that may be controlled by temperature or by enzymes or radiation or by other methods. The implantable biomaterial may be, for example, a polymer based on polycaprolactone, polyurethane, polytetrafluoroethylene silicone, inorganic salts such as calcium phosphate or hydroxyapatite. The implantable biomaterial may for example be ceramic-based or metal, such as aluminium, steel, titanium and/or alloys thereof, or a material made of ceramic or metal. Advantageously, when the material is ceramic or metal based or made of ceramic or metal, impregnation makes it possible to cover the outer surface of the material; the impregnation can advantageously be carried out by spraying.

According to the invention, the impregnating composition may have a concentration of biocompatible polymer as defined above of 0.1 μ g/mL to 1 μ g/mL.

According to the invention, the impregnating composition may have a 0.5mg.ml^-1To 20mg.mL^-1As defined above.

According to the invention, the duration of the impregnation can be from 5 minutes to 24 hours. Advantageously, the duration of the impregnation may depend on the structure of the graft and/or organ and/or implantable material.

Advantageously, impregnation furthermore makes it possible to improve the effectiveness of the implantation. Indeed, the inventors have surprisingly demonstrated that the presence of polymer and hyaluronic acid in the transplant and/or organ preservation solution advantageously allows a synergistic protective and anti-apoptotic effect.

Advantageously, the inventors have surprisingly demonstrated that the composition according to the invention makes it possible to achieve a synergistic effect, in particular over time, of the combination of the regenerating and protecting properties of a biocompatible polymer of general formula AaXxYy or AaXxYyZz (also known as RGTA) with the hydration and mechanical properties of natural or modified hyaluronic acid.

Furthermore, the inventors have demonstrated that the composition according to the invention advantageously makes it possible to prevent and/or treat defects and/or alterations associated with sequelae of any kind and stresses (mechanical, oxidative, radiation, etc.) and with ageing of tissues and organs of any origin, in vitro, ex vivo and in vivo, in humans and in animals.

As shown, the composition according to the invention can be used to prevent, slow down and improve markers associated with tissue aging, in particular as markers on the skin, for example to prevent, slow down and improve the loss of fine lines, rings, elasticity and flexibility or tone due to the presence of markers, skin dryness, skin thickness and/or pigmentation.

As shown, the composition according to the invention may be used for preventing, slowing down and/or treating joint pathologies, such as the degeneration of cartilage or synovial tissue.

As shown, the composition according to the invention may be used for preventing, slowing and/or treating alterations in the quality of the epithelium and/or corneal stroma and/or vitreous humor.

As shown, the composition according to the invention may be used for preventing, slowing and/or treating alterations in the quality of the epithelial and/or bladder matrix.

As shown, the composition according to the invention may be used for preventing, slowing down and/or treating all biological tissues and/or fluids in which hyaluronic acid naturally occurs and/or may alter the underlying cells and/or tissues producing said biological tissues and/or fluids and/or may modify and/or alter the quality and/or stability of hyaluronic acid.

As shown, the composition according to the invention advantageously and surprisingly allows a synergistic restoration of the aesthetic and functional quality of the skin as a whole and also with other tissues, and produces a rejuvenating effect and a functional restoration and an unexpected long-lasting effect that cannot be achieved individually for each of the products.

In addition to what has been shown, the spread of the effect achieved by the first administration of the composition according to the invention can be further improved, for example, by an iterative contribution, for example a local contribution, to the epithelium/epidermis/mucosa.