emulsion comprising a hydrogel and grease or a grease derivative

Abstract

The present invention relates to an emulsion comprising a hydrogel and fat or a fat derivative. In one embodiment, the emulsion further comprises at least one active ingredient, said active ingredient being selected from the group consisting of local anesthetics, vitamin C derivatives, anti-inflammatories, antioxidants, and mixtures thereof. The invention also relates to the process for preparing the emulsions according to the invention, characterized in that it comprises the following steps: Fat or a fat derivative is provided; a hydrogel is provided; the hydrogel and the fat or fat derivative are mixed aseptically; the mixture is emulsified until a homogeneous emulsion is obtained.The invention also relates to a kit for the preparation of an emulsion of fat or fat derivative and hyaluronic acid comprising a cartridge 4 and at least 2 syringes.

Description

Title of the invention: emulsion comprising a hydrogel and fat or a fat derivative

[0001] The present invention relates to an emulsion comprising a hydrogel and fat or a fat derivative.

[0002] In one embodiment, the emulsion further comprises at least one active agent, said active agent being chosen from the group consisting of local anesthetics, vitamin C derivatives, anti-inflammatories, antioxidants, and mixtures thereof.

[0003] Fat or fat derivative means fat for lipofilling which is fatty tissue which is mechanically emulsified or a very fluid substance obtained from emulsified fatty tissue whose fat cells have been crushed and filtered, commonly referred to as nanofat.

[0004] In one embodiment, the fat is lipofilling fat consisting of mechanically emulsified fatty tissue.

[0005] In one embodiment, the fat is a fat derivative, said derivative being a very fluid substance obtained from emulsified, liquefied fatty tissue whose fat cells have been crushed and filtered, commonly referred to as nanofat.

[0006] In one embodiment, the emulsion according to the invention is characterized in that the hydrogel / fat or fat derivative volume ratio is between 0.5 / 4.5 and 2 / 3.

[0007] In one embodiment, the emulsion according to the invention is characterized in that the hydrogel / fat or fat derivative volume ratio is 1 / 4.

[0008] Said hydrogel consists of at least one polysaccharide chosen from the group consisting of hyaluronic acid, keratan, heparin, cellulose, cellulose derivatives (in particular hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylmethylcellulose, carboxymethylcellulose), alginic acid, xanthan, carrageenan, chitosan, chondroitin, heparosan, and their biologically acceptable salts, alone or as a mixture.

[0009] In one embodiment, said polysaccharide is hyaluronic acid.

[0010] In one embodiment, said polysaccharide is hyaluronic acid or one of of its salts, alone or in a mixture.

[0011] In one embodiment, said polysaccharide is hyaluronic acid in the form of sodium or potassium salt.

[0012] In one embodiment, said polysaccharide is hyaluronic acid in sodium salt form.

[0013] In one embodiment, said polysaccharide is non-hyaluronic acid crosslinked or one of its salts, alone or in mixture

[0014] In one embodiment, said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or in a mixture.

[0015] In one embodiment, said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or as a mixture, and in that said crosslinking is carried out by means of at least one crosslinking agent.

[0016] In one embodiment, said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or as a mixture, and in that said crosslinking is carried out by means of at least one bi- or polyfunctional crosslinking agent.

[0017] In one embodiment, said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or as a mixture, and in that said crosslinking is carried out by means of at least one bifunctional crosslinking agent being butanedioldi-glycidyl ether (BDDE) or 1,2,7,8-diepoxyoctane.

[0018] In one embodiment, said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or in a mixture, and in that said crosslinking is carried out by means of BDDE.

[0019] In one embodiment, said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or in a mixture, and in that said crosslinking is carried out by means of a sodium or potassium trimetaphosphate.

[0020] When the polysaccharide and more particularly hyaluronic acid is crosslinked by means of a crosslinking agent, the crosslinking rate (x) is calculated theoretically by means of the following formula:

[0021] [Math.l] number of moles of crosslinking agent introduced into the reaction medium X = -----------—^7---—----------:-----—,---:— number of moles of repeating units introduced into the reaction medium

[0022] In the case of hyaluronic acid, the repeating unit is a disaccharide unit.

[0023] In one embodiment, the crosslinked hyaluronic acid has a crosslinking rate x of between 0.001 and 0.5.

[0024] In one embodiment, the crosslinked hyaluronic acid has a crosslinking rate x of between 0.01 and 0.4.

[0025] In one embodiment, the crosslinked hyaluronic acid has a crosslinking rate x of between 0.1 and 0.3.

[0026] In one embodiment, the crosslinked hyaluronic acid has a crosslinking rate x of 0.06.

[0027] In one embodiment, the crosslinked hyaluronic acid has a crosslinking rate x of 0.07.

[0028] In one embodiment, the crosslinked hyaluronic acid has a crosslinking rate culation x of 0.12.

[0029] In one embodiment, said polysaccharide is co-crosslinked hyaluronic acid or one of its salts, alone or in a mixture.

[0030] In one embodiment, said polysaccharide is hyaluronic acid chemically modified by substitution, crosslinked or non-crosslinked, or one of its salts, alone or in a mixture.

[0031] In one embodiment, said polysaccharide is doubly crosslinked hyaluronic acid as described in patent application WO2000 / 046253 in the name of Fermentech medical limited.

[0032] In one embodiment, said polysaccharide is a mixture of hyaluronic acids, or one of their salts, crosslinked and non-crosslinked.

[0033] In one embodiment, said polysaccharide is a mixture of crosslinked hyaluronic acids, or one of their salts.

[0034] In one embodiment, said polysaccharide is a mixture of hyaluronic acids, or one of their salts, crosslinked such as that described in patent application WO2009 / 071697 in the name of the applicant.

[0035] In one embodiment, said polysaccharide is a mixture of hyaluronic acids, obtained by mixing several hyaluronic acids, or one of their salts, of different molecular masses prior to their crosslinking, as described in patent application WO2004092222 in the name of Cornéal industrie.

[0036] In one embodiment, said polysaccharide is hyaluronic acid or one of its salts, substituted by a group providing lipophilic or moisturizing properties, such as for example substituted hyaluronic acids as described in patent application FR2983483 in the name of the applicant. In this application is described a process for simultaneous substitution and crosslinking of a polysaccharide via its hydroxyl functions, in aqueous phase, characterized in that it comprises the following steps: (i) a polysaccharide is provided in an aqueous medium, (ii) it is placed in the presence of at least one precursor of a substituent, (iii) it is placed in the presence of a crosslinking agent, and (iv) the substituted and crosslinked polysaccharide is obtained and isolated. These process steps can be perfectly implemented within the scope of the present invention.

[0037] In one embodiment, said polysaccharide is hyaluronic acid or one of its salts, grafted with glycerol, for example as described in application WO2017162676 in the name of MERZ.

[0038] In one embodiment, the molecular mass mw of the at least one hyaluronic acid is within a range of 0.01 MDa and 5 MDa.

[0039] In one embodiment, the molecular mass mw of the at least one hyaluronic acid is within a range of 0.1 MDa and 3.5 MDa.

[0040] In one embodiment, the molecular mass mw of the at least one luronic acid is in a range of 1 MDa and 3 MDa. hya-

[0041] In one embodiment, the molecular mass mw of the at least one hyaluronic acid is 1 MDa.

[0042] In one embodiment, the molecular mass mw of the at least one hya- luronic acid is 3 MDa.

[0043] In one embodiment, the concentration of hyaluronic acid [HA] is between 2 mg / g and 50 mg / g of total weight of said hydrogel.

[0044] In one embodiment, the concentration of hyaluronic acid [HA] is between 4 mg / g and 40 mg / g of total weight of said hydrogel.

[0045] In one embodiment, the concentration of hyaluronic acid [HA] is between 5 mg / g and 30 mg / g of total weight of said hydrogel.

[0046] In one embodiment, the concentration of hyaluronic acid [HA] is between 10 mg / g and 30 mg / g of total weight of said hydrogel.

[0047] In one embodiment, the concentration of hyaluronic acid [HA] is 20 mg / g of total weight of said hydrogel.

[0048] In one embodiment, the hydrogel is sterilized, that is to say that it undergoes a sterilization step after its preparation, said sterilization step being carried out by heat, by moist heat, by gamma(y) radiation, by accelerated electron beam, or by sterilizing filtration (0.22 pm) in the case of hydrogels based on non-crosslinked hyaluronic acid.

[0049] In one embodiment, said sterilization step is carried out by steam autoclaving.

[0050] In one embodiment, the steam autoclaving is carried out at a temperature of 121 to 134°C, for a time adapted to the temperature.

[0051] In one embodiment, the steam autoclaving is carried out at a temperature between 127 and 130°C for a duration between 1 and 20 min.

[0052] In one embodiment, the sterilizing value F0 is greater than 1 min at 121°C.

[0053] In one embodiment, said sterilization step is carried out by irradiation with gamma (γ) rays.

[0054] In one embodiment, the process for preparing the emulsions according to the invention further comprises at least one step of adding at least one active ingredient.

[0055] In one embodiment, the at least one active ingredient is added in powder form.

[0056] In one embodiment, the at least one active ingredient is added in the form of a solution or suspension.

[0057] In one embodiment, the at least one active ingredient is added in the form of a solution or suspension, in a solvent or solution chosen from the group consisting of water, aqueous saline solutions e.g. phosphate buffer solution e.g. PBS.

[0058] In one embodiment, the at least one active ingredient is added to the hyaluronic acid.

[0059] In one embodiment, the at least one active ingredient is added after the step of preparing the emulsions according to the invention.

[0060] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one active agent chosen from the group consisting of local anesthetics, vitamin C derivatives, anti-inflammatories, antioxidants, and mixtures thereof.

[0061] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic.

[0062] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of between 0.1 and 5%, relative to the total mass of said emulsion.

[0063] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of between 0.1 and 4%, relative to the total mass of said emulsion.

[0064] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of between 0.1 and 2%, relative to the total mass of said emulsion.

[0065] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of between 0.1 and 1%, relative to the total mass of said emulsion.

[0066] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of between 0.1 and 0.5%, relative to the total mass of said emulsion.

[0067] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of approximately 0.3%, relative to the total mass of said emulsion.

[0068] In one embodiment, the local anesthetic is selected from the group of amino esters.

[0069] In one embodiment, the amino ester is selected from the group comprising procaine, benzocaine, chloroprocaine and tetracaine in base or salt form, for example in hydrochloride form.

[0070] In one embodiment, the local anesthetic is selected from the group of amino-amides.

[0071] In one embodiment, the amino-amide is selected from the group consisting of lidocaine, mepivacaine, prilocaine, articaine, aptocaine, bupivacaine, etidocaine and ropivacaine in base or salt form, for example in hydrochloride form.

[0072] In one embodiment, the local anesthetic is selected from the group of amino ethers.

[0073] In one embodiment, the amino ether is selected from the group comprising diamocaine and pramocaine in base or salt form, for example in hydrochloride or cyclamate form.

[0074] In one embodiment, the amino ether is selected from the group consisting of lidocaine, mepivacaine, and their salts and isolated isomers.

[0075] In one embodiment, the amino ether is lidocaine.

[0076] In one embodiment, the amino ether is lidocaine or one of its pharmaceutical salts. maceutical acceptable.

[0077] In one embodiment, the amino ether is lidocaine hydrochloride.

[0078] In one embodiment, the amino ether is mepivacaine.

[0079] In one embodiment, the amino ether is mepivacaine or one of its salts. pharmaceutically acceptable.

[0080] In one embodiment, the amino ether is selected from the group consisting of racemic mepivacaine hydrochloride, racemic mepivacaine hydrochloride, (r)-mepivacaine hydrochloride, (s)-mepivacaine hydrochloride, (r)-mepivacaine and (s)-mepivacaine, or a pharmaceutically acceptable salt thereof.

[0081] In one embodiment, the amino ether is mepivacaine hydrochloride.

[0082] In one embodiment, the amino ether is (r)-mepivacaine hydrochloride.

[0083] In one embodiment, the amino ether is (s)-mepivacaine hydrochloride.

[0084] In one embodiment, the amino ether is mepivacaine hydrochloride. racemic.

[0085] In one embodiment, the amino ether is (r)-mepivacaine.

[0086] In one embodiment, the amino ether is (s)-mepivacaine.

[0087] In one embodiment, the amino ether is racemic mepivacaine.

[0088] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one amino-ether local anesthetic chosen from the group consisting of lidocaine, mepivacaine, and mixtures thereof.

[0089] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being lidocaine.

[0090] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being lidocaine to obtain a lidocaine concentration of between 0.1 and 5%, relative to the total mass of said emulsion.

[0091] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being lidocaine to obtain a lidocaine concentration of between 0.1 and 4%, relative to the total mass of said emulsion.

[0092] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being lidocaine to obtain a lidocaine concentration of between 0.1 and 2%, relative to the total mass of said emulsion.

[0093] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being lidocaine to obtain a lidocaine concentration of between 0.1 and 1%, relative to the total mass of said emulsion.

[0094] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being lidocaine to obtain a lidocaine concentration of between 0.1 and 0.5%, relative to the total mass of said emulsion.

[0095] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being lidocaine to obtain a local anesthetic concentration of approximately 0.3%, relative to the total mass of said emulsion.

[0096] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being mepivacaine.

[0097] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being mepivacaine to obtain a mepivacaine concentration of between 0.1 and 5%, relative to the total mass of said emulsion.

[0098] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being mepivacaine to obtain a mepivacaine concentration of between 0.1 and 4%, relative to the total mass of said emulsion.

[0099] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being mepivacaine to obtain a mepivacaine concentration of between 0.1 and 2%, relative to the total mass of said emulsion.

[0100] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being mepivacaine to obtain a mepivacaine concentration of between 0.1 and 1%, relative to the total mass of said emulsion.

[0101] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being mepivacaine to obtain a mepivacaine concentration of between 0.1 and 0.5%, relative to the total mass of said emulsion.

[0102] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being mepivacaine to obtain a local anesthetic concentration of approximately 0.3%, relative to the total mass of said emulsion.

[0103] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic being dyclonine in base or salt form, for example in hydrochloride form.

[0104] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one local anesthetic chosen from the group consisting of chlorobutanol, guafecainol and po-lidocanol.

[0105] In one embodiment, the local anesthetic is chlorobutanol.

[0106] In one embodiment, the local anesthetic is guafecainol.

[0107] In one embodiment, the local anesthetic is polidocanol.

[0108] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory agent.

[0109] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory agent chosen from the group consisting of steroidal and non-steroidal anti-inflammatories.

[0110] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group consisting of non-steroidal anti-inflammatories.

[0111] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group comprising salicylate anti-inflammatories, propionic derivatives, indole derivatives, pyrazole derivatives, oxicams and coxibs.

[0112] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group comprising diclofenac, nimesulfide, niflumic acid, mefenamic acid and nabumetone, alone or as a mixture.

[0113] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one salicylated anti-inflammatory chosen from the group comprising diflunisal, benorilate and aspirin, alone or as a mixture.

[0114] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group of propionic derivatives comprising alminoprofen, ketoprofen, ibuprofen, naproxen, flurbiprofen and tiaprofenic acid, alone or as a mixture.

[0115] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group of indole derivatives comprising indomethacin, sulindac and etodolac, alone or as a mixture.

[0116] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group of pyrazole derivatives including in particular phenylbutazone.

[0117] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group of oxicams comprising piroxicam, tenoxicam and meloxicam, alone or as a mixture.

[0118] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory chosen from the group of coxibs comprising celecoxib, etoricoxib and rofecoxib, alone or as a mixture.

[0119] In one embodiment, the concentration of non-steroidal anti-inflammatory drugs in an emulsion according to the invention is between 0.01 and 2000 mg / g.

[0120] In one embodiment, the concentration of non-steroidal anti-inflammatory drugs in an emulsion according to the invention is between 0.1 and 1000 mg / g.

[0121] In one embodiment, the concentration of non-steroidal anti-inflammatory drugs in an emulsion according to the invention is between 0.5 and 500 mg / g.

[0122] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one steroidal anti-inflammatory agent.

[0123] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one steroidal anti-inflammatory agent chosen from the group comprising dexamethasone, prednisolone, corticosterone, budesonide, sulfasalazine, mesalamine, cetirizine, diphenhydramine, antipyrine, methyl salicylate, loratadine, thymol, carvacrol, bisabolol, allantoin, eucalyptol, phenazone (antipyrine), propy-phenazone, alone or as a mixture.

[0124] In one embodiment, the concentration of steroidal anti-inflammatories in an emulsion according to the invention is between 0.01 and 2000 mg / g.

[0125] In one embodiment, the concentration of steroidal anti-inflammatories in an emulsion according to the invention is between 0.1 and 1000 mg / g.

[0126] In one embodiment, the concentration of steroidal anti-inflammatories in an emulsion according to the invention is between 0.5 and 500 mg / g.

[0127] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory agent chosen from the group consisting of sucrose octasulfate and its salts.

[0128] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory agent chosen from the group consisting of sucrose octasulfate and its sodium and potassium salts.

[0129] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory water-soluble salt of sucrose octasulfate chosen from the group consisting of alkali metal salts, alkaline earth metal salts, silver salts, ammonium salts, amino acid salts.

[0130] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti-inflammatory water-soluble salt of sucrose octasulfate chosen from the group consisting of alkali metal salts or alkaline earth metal salts.

[0131] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one anti- flammatory water-soluble salt of sucrose octasulfate selected from the group consisting of sodium salt of sucrose octasulfate or potassium salt of sucrose octasulfate.

[0132] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antimicrobial.

[0133] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antimicrobial chosen from the group comprising gentamicin, silver sulfadiazine, metronidazole, fucidin, bacitracin, eosin, povidone iodine, copper gluconate, zinc gluconate, manganese gluconate or their salts, alone or as a mixture.

[0134] In one embodiment, the concentration of antimicrobials in an emulsion according to the invention is between 0.1 and 200 mg / g.

[0135] In one embodiment, the concentration of antimicrobials in an emulsion according to the invention is between 0.5 and 100 mg / g.

[0136] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one glycoside or glycoside derivative.

[0137] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one glycoside or glycoside derivative chosen from the group comprising D-glucopyranose, 1,4 glycoside, esculin, hesperidin, diosmin, arbutin, skimmin or aloin, alone or in mixtures.

[0138] In one embodiment, the concentration of glycosides in an emulsion according to the invention is between 0.1 and 200 mg / g.

[0139] In one embodiment, the concentration of glycosides in an emulsion according to the invention is between 0.5 and 100 mg / g.

[0140] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one tissue moisturizer or regenerator.

[0141] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one moisturizer or tissue regenerator chosen from the group consisting of macro-elements.

[0142] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one macroelement chosen from the group comprising iron, calcium, copper, zinc, manganese, magnesium or potassium gluconates, trimethylsilanol, trimethylsilanolate, potassium trimethylsilanolate, methylsilanol mannuronate, sodium monoethyl-trisilanol orthohydroxybenzoate, alone or as a mixture.

[0143] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one tissue moisturizer or regenerator chosen from the group consisting of essential amino acids.

[0144] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one essential amino acid chosen from the group comprising isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine, alone or as a mixture.

[0145] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one tissue moisturizer or regenerator chosen from the group consisting of semi-essential amino acids.

[0146] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one semi-essential amino acid chosen from the group comprising arginine and histidine, alone or as a mixture.

[0147] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one tissue moisturizer or regenerator chosen from the group consisting of non-essential amino acids.

[0148] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one non-essential amino acid chosen from the group comprising alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, tyrosine, alone or as a mixture.

[0149] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one moisturizer or tissue regenerator chosen from the group consisting of vitamins.

[0150] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one vitamin chosen from the group consisting of retinol, thiamine, riboflavin, nicotinamide, adenine, calcium pantothenate, pyridoxine, inositol, biotin, folic acid, para-aminobenzoic acid, cobalamin, vitamin C, choline chloride, alone or as a mixture.

[0151] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one tissue moisturizer or regenerator chosen from the group consisting of nucleic acids.

[0152] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one nucleic acid chosen from the group consisting of deoxyadenosine, deoxycytidine, deoxyguanosine, deoxythymidine, methylcytosine, alone or in mixture.

[0153] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one tissue moisturizer or regenerator chosen from the group consisting of coenzymes.

[0154] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one coenzyme chosen from the group consisting of thiamine pyrophosphate, coenzyme A, FAD, NAD, NADP, UTP, alone or as a mixture.

[0155] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one tissue moisturizer or regenerator chosen from the group consisting of deoxythymidine, glutathione, sodium pyruvate, lipoic acid and putrescine, alone or as a mixture.

[0156] In one embodiment, the concentration of tissue moisturizers or regenerators in an emulsion according to the invention is between 0.01 and 500 mg / g.

[0157] In one embodiment, the concentration of tissue moisturizers or regenerators in an emulsion according to the invention is between 0.1 and 200 mg / g.

[0158] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant.

[0159] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of polyols.

[0160] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol chosen from the group consisting of mannitol, sorbitol, propylene glycol, xylitol, glycerol, maltitol, lactitol and erythritol.

[0161] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol chosen from the group consisting of mannitol, sorbitol, maltitol and glycerol, alone or as a mixture.

[0162] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol chosen from the group consisting of mannitol, sorbitol and maltitol, alone or as a mixture.

[0163] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of between 0.1 mg / ml and 50 mg / ml, relative to the total mass of said emulsion.

[0164] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of between 5 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0165] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of between 10 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0166] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of between 20 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0167] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of between 30 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0168] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol being mannitol.

[0169] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of between 5 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0170] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of between 10 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0171] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of between 20 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0172] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of between 30 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0173] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol being sorbitol.

[0174] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of between 5 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0175] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of between 10 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0176] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of between 20 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0177] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of between 30 mg / ml and 40 mg / ml, relative to the total mass of said emulsion.

[0178] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol being maltitol.

[0179] In one embodiment, the process for preparing an emulsion according to the invention further comprises at least one step of adding at least one polyol being glycerol.

[0180] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding a mixture of mannitol and sorbitol.

[0181] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of vitamin C derivatives.

[0182] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of vitamin C derivatives comprising magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl-2-glucoside, and their mixture.

[0183] In one embodiment, said at least one vitamin C derivative is magnesium ascorbyl phosphate.

[0184] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of vitamin E derivatives and tocopherols.

[0185] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of carotenoids and retinoids and their derivatives.

[0186] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of carotenoids and retinoids and their derivatives comprising retinol, retinoic acid, retinal, retinol esters and carotene.

[0187] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of pseudo-tripeptides.

[0188] In one embodiment, the pseudo-tripeptide is glutathione.

[0189] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group comprising the different forms of coenzyme Q10, ubiquinone or ubiquinol.

[0190] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one vitamin.

[0191] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one vitamin chosen from the group comprising retinol, thiamine, riboflavin, nicotinamide, dexpenthenol, pyridoxine, ascorbic acid, ergocalciferol, tocopherol, biotin and folic acid alone or as a mixture.

[0192] In one embodiment, the concentration of vitamins in an emulsion according to the invention is between 0.01 and 200 mg / g.

[0193] In one embodiment, the concentration of vitamins in an emulsion according to the invention is between 0.01 and 100 mg / g.

[0194] In one embodiment, the concentration of vitamins in an emulsion according to the invention is between 0.5 and 50 mg / g.

[0195] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one amino acid.

[0196] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one amino acid chosen from the group consisting of essential amino acids, semi-essential amino acids and non-essential amino acids, alone or as a mixture.

[0197] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one amino acid chosen from the group of essential amino acids.

[0198] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one essential amino acid chosen from the group comprising isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine, alone or as a mixture.

[0199] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one amino acid chosen from the group of semi-essential amino acids.

[0200] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one semi-essential amino acid chosen from the group comprising arginine and histidine, alone or as a mixture.

[0201] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one amino acid chosen from the group of non-essential amino acids.

[0202] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one non-essential amino acid chosen from the group comprising alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, tyrosine, alone or as a mixture.

[0203] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one amino acid chosen from the group comprising hydroxyproline, taurine and ornithine, alone or as a mixture.

[0204] In one embodiment, the concentration of amino acids in an emulsion according to the invention is between 0.01 and 150 mg / g.

[0205] In one embodiment, the concentration of amino acids in an emulsion according to the invention is between 0.01 and 100 mg / g.

[0206] In one embodiment, the concentration of amino acids in an emulsion according to the invention is between 0.5 and 50 mg / g.

[0207] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one vasoconstrictor.

[0208] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one vasoconstrictor chosen from the group comprising naphazoline, epinephrine, methoxamine, methylnorepinephrine, norepinephrine, oxymethazoline, phenylephrine, pseudoephedrine, synephrine, cirazoline and xylometazoline.

[0209] In one embodiment, the concentration of vasoconstrictors in a emulsion according to the invention is between 0.01 and 3 mg / g.

[0210] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one vasodilator.

[0211] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one vasodilator chosen from the group comprising adenosine, nicotinic acid, minoxidil and diazoxide, alone or as a mixture.

[0212] In one embodiment, the concentration of vasodilators in an emulsion according to the invention is between 0.01 and 10 mg / g.

[0213] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antihemorrhagic or hemostatic agent.

[0214] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antihemorrhagic or hemostatic agent chosen from the group comprising aminocaproic acid or tranexamic acid, alone or as a mixture.

[0215] In one embodiment, the concentration of anti-hemorrhagic or hemostatic agents in an emulsion according to the invention is between 0.01 and 5 mg / g.

[0216] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant and at least one local anesthetic.

[0217] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant chosen from the group of polyols and at least one local anesthetic chosen from the group of amino-amides.

[0218] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant, at least one vitamin and at least one tissue regenerator.

[0219] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one amino acid, at least one vitamin and at least one tissue regenerator.

[0220] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one antioxidant, at least one amino acid, at least one vitamin and at least one tissue regenerator.

[0221] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one active agent chosen from the group consisting of heat-sensitive active agents.

[0222] In one embodiment, the at least one heat-sensitive active agent is added during the step of preparing the emulsions according to the invention, namely during the step of mixing the hydrogel and the fat or fat derivative.

[0223] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding a so-called heat-sensitive active ingredient of natural origin.

[0224] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding a so-called heat-sensitive active ingredient of synthetic origin.

[0225] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one heat-sensitive active ingredient chosen from the group consisting of peptides, hormones, proteins, growth factors, antibodies and vitamins, alone or as a mixture.

[0226] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one heat-sensitive active agent chosen from the group consisting of peptides.

[0227] In one embodiment, the added thermosensitive active is a peptide.

[0228] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one heat-sensitive active ingredient chosen from the group consisting of hormones.

[0229] In one embodiment, the added heat-sensitive active is a hormone.

[0230] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one heat-sensitive active ingredient chosen from the group consisting of proteins.

[0231] In one embodiment, the added thermosensitive active is a protein.

[0232] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one heat-sensitive active ingredient chosen from the group consisting of growth factors.

[0233] In one embodiment, the added heat-sensitive active is a growth factor.

[0234] In one embodiment, the method for preparing an emulsion according to the invention further comprises at least one step of adding at least one heat-sensitive active agent chosen from the group consisting of antibodies.

[0235] In one embodiment, the added thermosensitive active is an antibody.

[0236] In one embodiment, the method of preparing an emulsion according to the invention further comprises at least one step of adding at least one heat-sensitive active ingredient chosen from the group consisting of vitamins.

[0237] In one embodiment, the vitamins are selected from the group comprising retinol, thiamine, riboflavin, nicotinamide, dexpenthenol, pyridoxine, ascorbic acid, ergocalciferol, tocopherol, biotin and folic acid alone or in combination.

[0238] The applications targeted are more particularly the following pathologies or treatments: • Aesthetic injections in the face: mesotherapy, wrinkle filling, skin defects or volume (cheekbones, chin, lips); • Body volume injections: breast and buttock augmentation, G-spot augmentation, vaginoplasty, vaginal labia reconstruction, penis enlargement; • Treatment of osteoarthritis, injection into the joint to replace or supplement deficient synovial fluid; • Periurethral injection for the treatment of urinary incontinence due to sphincter insufficiency; • Post-surgical injection to prevent adhesions, particularly peritoneal; • Injection following presbyopia surgery using laser scleral incisions; • Injection into the vitreous cavity; • Injection during cataract surgery; • Injection into the genitals; • Injection for tissue spacing.

[0239] More particularly, in cosmetic surgery, depending on its viscoelastic and remanence properties, the emulsion according to the invention may be used: • to improve the hydration and quality of the skin by cutaneous mesotherapy of the face, neck, décolleté or hands. In this case the product is injected using a needle with a diameter varying between 27 and 32G and lengths generally varying between 1 / 8” and L?”. The composition may be injected either by hand or by means of automatic devices such as injector pens. • for filling fine, medium or deep wrinkles, and to be injected with fine diameter needles (27 Gauge to 30G most commonly, lengths generally being 1 / 2''); • as a volumizer with an injection either by needles of larger diameter, 25 to 27G Gauge for example, and longer (30 to 40 mm for example), or by cannulas of length mainly between 40 and 70mm and diameter 22 to 25G; in this case, its cohesive nature will ensure its maintenance at the injection site.

[0240] The emulsion according to the invention also finds an important application in

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[0251] joint surgery and dental surgery for filling periodontal pockets for example. These examples of use are in no way limiting, the emulsion according to the present invention being more broadly intended for: • fill volumes; • generate spaces between certain tissues; • replace deficient physiological fluids. The invention also relates to the process for preparing the emulsions according to the invention, characterized in that it comprises the following steps: a. Fat or fat derivative is available, b. We have a hydrogel, c. The hydrogel and the fat or fat derivative are mixed aseptically, d. The mixture is emulsified until a homogeneous emulsion is obtained. In one embodiment, the hydrogel contains an active ingredient as previously defined. In one embodiment, an active ingredient is provided which is introduced at the time of mixing the hydrogel and the fat or fat derivative. Fat, fat derivative, hydrogel and actives are as previously defined. The invention also relates to a kit for the preparation of an emulsion of fat or fat derivative and hyaluronic acid comprising a cartridge 4 and at least 2 syringes. In one embodiment of the kit, the cartridge (4) comprises at least one hydrogel. In one embodiment the kit includes at least 3 syringes. In one embodiment the kit includes at least 4 syringes. Kit 1: syringes 1 and 2 + cartridge 4 filled with hyaluronic acid. Syringe 1 (medium volume syringe) is empty or full of fatty tissue, cartridge 4 contains the hyaluronic acid gel (crosslinked or not) and syringe 2 (large volume syringe) is empty and its volume is equivalent to the addition of the volume of syringe 1 and cartridge 4 (VI + V4). 1. Use syringe 1 to collect fat for lipofilling (medium size syringe). 2. Take cartridge 4 pre-filled with hyaluronic acid and connect syringe 1 to cartridge 4 using Luer lock connectors 1a and 4a. 3. Add to the second tip 4-b, of cartridge 4, the syringe 2 (syringe large volume VI + V4) and operate the pistons 1b and 2b, of the two syringes 1 and 2, with back and forth movements to create the emulsion between the fat for lipofilling and the hyaluronic acid gel. 4. After several back and forth movements (< 15 movements), completely draw the emulsion into syringe 2 (large volume syringe). 5. Disconnect syringe 2 from the cartridge, the emulsion contained in this syringe 2 is ready to be injected. 6. Fit a cannula onto syringe 2, tip 2a, to inject the fat emulsion for lipofilling and hyaluronic acid. The choice of these cannulas is left to the surgeon's discretion depending on the area to be treated.

[0252] Optional steps can be carried out to allow the incorporation of active ingredients into the hyaluronic acid and fat emulsion for lipofilling. These new steps can be incorporated at two separate times. - Can be carried out before step 3: a) After several back and forth movements (< 15 movements), completely draw the emulsion into syringe 2 (large volume syringe).

[0253] b) Disconnect syringe 1 from tip 4a of the cartridge and connect syringe 5, containing the active ingredients, to this same cartridge on tip 4b.

[0254] c) Empty the contents of syringe 5 into the cartridge, then operate the pistons 2b and 5b of syringes 2 and 5 to mix the emulsion with the active ingredient.

[0255] d) Completely draw the mixture into syringe 2

[0256] where - Can be carried out after step 4: a) Disconnect syringe 2 from the cartridge.

[0257] b) Connect together syringe 2, containing the emulsion of hyaluronic acid and fat for lipofilling, and syringe 5, containing the active ingredient, via a double Luer Lock connector connected to the tips 2a and 5a of each of the two syringes.

[0258] c) Carry out back and forth movements (< 15 movements), to mix the emulsion and the active ingredient by actuating the pistons 2b and 5b of each of the syringes.

[0259] d) Completely draw up the emulsion mixed with the active ingredient into syringe 2.

[0260] e) Disconnect syringe 2, the emulsion contained in this syringe 2 is ready to be injected.

[0261] Kit 2: syringes 1, 2 and 3 + cartridge 4

[0262] Syringe 1 (medium volume syringe) is used to collect fat for lipofilling, syringe 3 (small volume syringe) contains the hyaluronic acid gel (crosslinked or not), cartridge 4 and syringe 2 (large volume syringe) are empty. 1. Use syringe 1 to collect fat for lipofilling (medium size syringe). 2. Connect syringe 1 to empty cartridge 4 using connectors 1a and 4a. 3. Connect syringe 3 (small syringe), containing the HA gel, to the empty cartridge 4 using connectors 3a and 4b. 4. Fill the empty cartridge 4 with the contents of syringe 3 (HA gel). 5. Disconnect syringe 3 from tip 4b and connect the syringe 2 (larger syringe VI + V4) using connector 2a. 6. Make back and forth movements on the pistons 1b and 2b, of the two syringes 1 and 2, to make the emulsion (< 15 movements). 7. Completely fill syringe 2 with the contents of syringe 1 and cartridge 4. 8. Disconnect syringe 2 from the cartridge, the emulsion contained in syringe 2 is ready to be injected. 9. Fit a cannula onto syringe 2, tip 2a, to perform the injections of the fat emulsion for lipofilling and hyaluronic acid. The choice of these cannulas is left to the surgeon's discretion depending on the area to be treated.

[0263] In one embodiment, a syringe 5 may be added to kit 1 or kit 2, for example to incorporate an active ingredient as defined above.

[0264] Optional steps can be carried out to allow the incorporation of active ingredients into the hyaluronic acid and fat emulsion for lipofilling. These new steps can be incorporated at two separate times. - Can be carried out after step 6: a) Completely fill syringe 3 with the contents of syringe 1 and cartridge 4.

[0265] b) Disconnect the syringe 3 and connect in its place, on the tip 4b of the cartridge, the syringe 5 via the tip 5a.

[0266] c) Empty the contents of syringe 5 into cartridge 4.

[0267] d) Actuate the pistons 2b and 5b of the syringes 2 and 5 to make back and forth movements (< 15 movements) to mix the emulsion and the active ingredient.

[0268] e) Completely fill syringe 2 with the contents of syringe 5 and cartridge 4.

[0269] where - Can be carried out after step 8: a) Disconnect syringe 2 from the cartridge.

[0270] b) Connect together syringe 2, containing the emulsion of hyaluronic acid and fat for lipofilling, and syringe 5, containing the active ingredient, by via a double Luer Lock connector, connected to tips 2a and 5a of each of the two syringes.

[0271] c) Carry out back and forth movements (< 15 movements), to mix the emulsion and the active ingredient by actuating the pistons 2b and 5b of each of the syringes.

[0272] d) Completely draw up the emulsion mixed with the active ingredient into syringe 2.

[0273] e) Disconnect syringe 2, the emulsion contained in this syringe 2 is ready to be injected. DESCRIPTION OF FIGURES

[0274] [Fig.l] represents a cartridge 4 and 4 syringes 1, 2, 3 and 5.

[0275] The following examples are given to illustrate the invention

[0276] EXAMPLES:

[0277] Example 1: Hyaluronic acid gels

[0278] A commercial non-crosslinked hyaluronic acid gel, the product Stylage® Hydro (VIVACY) and a commercial crosslinked hyaluronic acid gel comprising a local anesthetic, the product Juvederm Ultra® 2 (ALLERGAN), were used for the preparation of the fat and hyaluronic acid emulsions according to the invention. These commercial hyaluronic acid gels are available in 1 mL syringes.

[0279] Example 2: Process for recovering the fat used for the preparation of the fat emulsion.

[0280] Fatty tissue, called lipofilling fat, was harvested during surgery with the appropriate consent of the donor, preferably from the abdomen or knees.

[0281] The fat sampling was carried out following standard surgical techniques under anesthesia according to a protocol involving in particular identification of the area of ​​the body to be sampled, making an incision in the sampling area followed or not by infiltration with Klein serum, sampling the fat for lipofilling using a specific Tonnard cannula and transferring the fat from the cannula to a sterile syringe under vacuum using back-and-forth movements in the tissues and oscillating movements of the cannula to avoid bleeding and to obtain a regular appearance after sampling.

[0282] The choice of material used for the sample as well as its technical characteristics is left to the surgeon's discretion depending on the area to be treated.

[0283] The grease-filled syringe is ready to use or can be stored in the cold before use.

[0284] Example 3: Process for preparing a fat emulsion for lipofilling

[0285] Recovered fat for lipofilling is taken using a sterile syringe of 5 mL equipped with a Luer lock system.

[0286] This sterile syringe is connected to one of the inlets of a sterile 3-way valve or to one of the inlets of a sterile double Luer lock connector, while to one of the other inlets is connected an empty sterile 5 mL syringe equipped with the Luer lock system.

[0287] In order to obtain a homogeneous emulsion based solely on fat for lipofilling, rapid back-and-forth movements of the pistons between the two sterile syringes connected to each other by the 3-way valve or by the double Luer lock connector are carried out. At least 40 back-and-forth movements are necessary to obtain a satisfactory emulsion of fat for lipofilling.

[0288] Example 4: Process for preparing a fat emulsion for lipofilling and hyaluronic acid according to the invention

[0289] 4 mL of recovered fat for lipofilling are taken using a syringe sterile 5 mL bottle equipped with a Luer lock system.

[0290] This sterile syringe is connected to one of the inlets of a sterile 3-way valve or to one of the inlets of a sterile double Luer lock connector, while to one of the other inlets is connected a syringe containing 1 mL of hyaluronic acid gel.

[0291] The hyaluronic acid gel is then introduced into the sterile syringe containing the fat for lipofilling.

[0292] The syringe containing the hyaluronic acid gel is replaced by an empty sterile 5 mL syringe equipped with a Luer lock system.

[0293] In order to obtain a homogeneous emulsion based on fat for lipofilling and hyaluronic acid, rapid back and forth movements of the pistons between the two sterile syringes connected to each other by the 3-way valve or by the double Luer lock connector are carried out. At least 40 back and forth movements are necessary to obtain a satisfactory emulsion of fat for lipofilling and hyaluronic acid.

[0294] In a variant, the homogeneous emulsion is obtained using the kit comprising the cartridge as defined above.

[0295] Example 5: Storage stability of a fat emulsion for lipofilling and hyaluronic acid according to the invention

[0296] The stability of a fat emulsion for lipofilling and hyaluronic acid prepared according to the method of Example 2 from the product Stylage® Hydro was monitored visually during horizontal storage on a table at 20°C, 2 hours and 4 hours after its preparation.

[0297] The stability of a fat emulsion for lipofilling prepared according to the method of Example 1 was also evaluated in parallel according to the same protocol.

[0298] The results of this stability study are described in Table 1.

[0299] [Tables 1] Composition Fat emulsion for lipofilling Fat emulsion for lipofilling and hyaluronic acid Observation 2h Formation of two phases Homogeneous mixture 4h Formation of two phases Homogeneous mixture

[0300] A pure fat emulsion for lipofilling degrades rapidly as indicated by the formation of two phases after 2 hours of storage at room temperature.

[0301] The fat emulsion for lipofilling and hyaluronic acid according to the invention is stable at room temperature for at least 4 hours.

[0302] The stability of the fat emulsion for lipofilling and hyaluronic acid according to the invention offers flexibility and comfort to the surgeon in the context of its use during a surgical procedure.

[0303] Example 6: injectability of fat emulsions for lipofilling and hyaluronic acid according to the invention

[0304] The injectability of a fat emulsion for lipofilling and hyaluronic acid prepared according to the method of Example 2 from the product Stylage® Hydro and of a fat emulsion for lipofilling and hyaluronic acid prepared according to the method of Example 2 from the product Juvederm Ultra® 2 was evaluated through 27G and 25G cannulas from freshly prepared emulsions and after 4h30 of storage at 20°C.

[0305] For comparison, the injectability of a freshly prepared fat emulsion for lipofilling was evaluated through 27G and 25G cannulas.

[0306] The injectability results are shown in Table 2.

[0307] [Tables2] Composition Fat emulsion for lipofilling Fat emulsion for lipofilling and hyaluronic acid from the product Stylage® Hydro Fat emulsion for lipofilling and hyaluronic acid from the product Juvederm Ultra® 2 Aging of the emulsion Fresh Fresh 4h30 Fresh 4h30 Observation 27 G cannula Difficult to inject Injectable Injectable Injectable Injectable 25 G cannula Difficult to inject Injectable Injectable Injectable Injectable

[0308] The results obtained show that the fat emulsions for lipofilling and hyaluronic acid according to the invention allow the surgeon to use cannulas of a smaller size than those which can be used for the injection of a pure fat emulsion for lipofilling.

[0309] The fat emulsions for lipofilling and hyaluronic acid according to the invention can still be injected with small cannulas at least 4.5 hours after their preparation, which provides comfort and flexibility in terms of use during a surgical procedure.

[0310] Example 7: appearance of fat emulsions for lipofilling and hyaluronic acid according to the invention after passage through a cannula

[0311] The stability of fresh emulsions according to the invention and 4.5 hours after their preparation was evaluated by visual observation of the deposit obtained after passing through a 25G cannula.

[0312] The emulsions tested are identical to those of example 4.

[0313] The observation results of these different emulsions are presented in the table 3.

[0314] [Table 3]. Composition Fat emulsion for lipofilling Fat emulsion for lipofilling and hyaluronic acid from the product Stylage® Hydro Fat emulsion for lipofilling and hyaluronic acid from the product Juvederm Ultra® 2 Aging of the emulsion Fresh Fresh 4h30 Fresh 4h30 Observation Foamy appearance Smooth appearance Liquid emulsion with visible spreading Smooth appearance Emulsion without apparent spreading

[0315] The fat emulsions for lipofilling and hyaluronic acid according to the invention have better resistance after passing through a cannula than the pure fat emulsion for lipofilling, even after storage at room temperature.

[0316] Example 8: rheological properties of fat emulsions for lipofilling and hyaluronic acid according to the invention

[0317] The viscoelastic properties were measured using a TA instrument AR2000 rheometer. The measurements are carried out at 25 °C with a 2 ° 40 mm conical geometry using a frequency sweep from 0.08 to 5 Hz with a deformation of 0.8%.

[0318] Viscoelastic properties were measured for a grease emulsion for li- pofilling prepared according to example 1 and for a fat emulsion for lipofilling and hyaluronic acid prepared according to example 2 from the product Stylage® Hydro.

[0319] The results of the measurements of G' and Tan ô at 1 Hz, as well as the cut-off frequency of the G' and G", / cut-off curves, of the different samples studied are presented in Table 4 below.

[0320] [Tables4] Composition Observation G' (1 Hz) Tanô(1 Hz) / cutoff (Hz) Fat emulsion for lipofilling Without prior injection 6.2 Pa 0.35 - Fat emulsion for lipofilling and hyaluronic acid from the Stylage® Hydro product Without prior injection 22.8 Pa 0.87 0.6 After injection (25G cannula) 22.2 Pa 0.87 0.4 Stylage® Hydro gel Without prior injection 77.7 Pa 0.82 0.6

[0321] The rheological properties of the fat emulsion for lipofilling and hyaluronic acid according to the invention prepared from the Stylage® Hydro product are not affected by passage through a 25G size cannula.

[0322] It can be noted that the fat emulsion for lipofilling and hyaluronic acid according to the invention prepared from the product Stylage® Hydro has a Tan ô value close to that of the commercial hyaluronic acid gel Stylage® Hydro.

[0323] The rheological properties of the fat emulsion for lipofilling and hyaluronic acid according to the invention prepared from the Stylage® Hydro product are much more interesting than those of the pure fat emulsion for lipofilling.

[0324] Example 9: Microscopic analysis of fat emulsion for lipofilling and hyaluronic acid according to the invention

[0325] The microscope analyses were carried out using an Axio scope Al optical microscope from Zweiss, equipped with Filtrex software and with x20 magnification.

[0326] Three types of samples were analyzed under a microscope: a sample of a fat sample for lipofilling, a sample of a fat emulsion for lipofilling prepared according to example 1, a sample of a fat emulsion for lipofilling and hyaluronic acid according to the invention prepared according to example 2 from the product Stylage® Hydro.

[0327] The results of the various microscope observations of the samples are presented in Table 5 below.

[0328] [Table 5]. Sample Fat for lipofilling Fat emulsion for lipofilling Fat emulsion for lipofilling and hyaluronic acid Observations Presence of large fat globules stuck together Small unstable fat globules, stuck together with a tendency to group together Small stable fat globules spaced apart by a "protective" matrix Shape of particles Round - Round The fat and hyaluronic acid emulsion according to the invention has a more regular appearance with small fat globules incorporated in a hyaluronic acid matrix.

Claims

Claims

1. Emulsion consisting of a hydrogel and fat or fat derivative and optionally an active ingredient, characterized in that: - the fat or fat derivative is lipofilling fat consisting of mechanically emulsified fatty tissue, and - the hydrogel consists of at least one polysaccharide, said polysaccharide being hyaluronic acid or one of its biologically acceptable salts, alone or in a mixture, and - the concentration of hyaluronic acid [HA] in the hydrogel is between 2 mg / g and 50 mg / g of total weight of said hydrogel, - the active ingredient is chosen from the group consisting of local anesthetics, vitamin C derivatives chosen from magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl-2-glucoside and mixtures thereof, anti-inflammatory agents, antioxidants, and mixtures thereof.

2. Emulsion according to claim 1, characterized in that the fat derivative is a very fluid substance obtained from emulsified, liquefied fatty tissue whose fat cells have been crushed and filtered, commonly referred to as nanofat.

3. Emulsion according to any one of the preceding claims, characterized in that it comprises an active ingredient.

4. Emulsion according to claim 1, characterized in that said polysaccharide is hyaluronic acid in the form of sodium or potassium salt.

5. Emulsion according to claim 4, characterized in that said polysaccharide is non-crosslinked hyaluronic acid or one of its salts, alone or as a mixture.

6. Emulsion according to claim 4, characterized in that said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or as a mixture.

7. Emulsion according to claim 6, characterized in that said polysaccharide is crosslinked hyaluronic acid or one of its salts, alone or as a mixture, and in that said crosslinking is carried out by means of at least one bifunctional crosslinking agent being butanedioldiglycidyl ether (BDDE) or 1,2,7,8-diepoxyoctane.

8. Emulsion according to any one of claims 4 to 7, characterized in that the molecular mass MW of the at least one hyaluronic acid is within a range of 0.01 MDa and 5 MDa.

9. Emulsion according to any one of the preceding claims, characterized in that the hydrogel is sterilized, that is to say that it undergoes a sterilization step after its preparation, said sterilization step being carried out by heat, by moist heat, by gamma radiation (y), by accelerated electron beam, or by sterilizing filtration (0.22 pm) in the case of hydrogels based on non-crosslinked hyaluronic acid.

10. Emulsion according to any one of the preceding claims, characterized in that the hydrogel / fat or fat derivative volume ratio is between 0.5 / 4.5 and 2 / 3.

11. Process for preparing an emulsion according to any one of the preceding claims, characterized in that it comprises at least the following steps: a. Fat or fat derivative is provided, b. A hydrogel is provided, c. The hydrogel and the fat or fat derivative are mixed aseptically, characterized in that the fat or fat derivative is fat for lipofilling consisting of mechanically emulsified fatty tissue, d. The mixture is emulsified until a homogeneous emulsion is obtained.

12. Kit for the preparation of an emulsion according to any one of the preceding claims, characterized in that it comprises a cartridge (4) and at least 2 syringes, characterized in that the cartridge (4) comprises at least one hydrogel.

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