Emulsion comprising hydrogel and fat or fat derivative

Abstract

The present invention relates to an emulsion, gelling emulsion or gel comprising a hydrogel and a fat or fat derivative. In one embodiment, the emulsion further comprises at least one active ingredient selected from the group consisting of local anesthetics, vitamin C derivatives, anti-inflammatory agents, antioxidants, and mixtures thereof. The invention also relates to a method for preparing an emulsion, a gelling emulsion or a gel according to the invention, characterized in that said method comprises the following steps: e) providing a fat or a fat derivative; f) providing a hydrogel; g) aseptically mixing the hydrogel with the fat or fat derivative; h) emulsifying the mixture until an emulsion, a gelling emulsion or a homogeneous gel is obtained. The invention also relates to a kit for preparing an emulsion, a gelling emulsion or a gel of fat or fat derivatives and hyaluronic acid, said kit comprising a cartridge 4 and at least 2 injectors, such that it can be ensured that the process and the gel obtained are sterile.

Description

[0001] The present invention relates to a spreadable gel in the form of an emulsion comprising a hydrogel and a fat or a fat derivative.

[0002] The present invention therefore relates to a gelled emulsion comprising a hydrogel and a fat or a fat derivative.

[0003] The invention also relates to an emulsion comprising a hydrogel and a fat or a fat derivative.

[0004] Fat or fat derivatives are understood to mean fat filling fat, MICROFAT, or NANOFAT.

[0005] In one embodiment, the fat is lipoflavor fat, MICROFAT, or NANOFAT.

[0006] Fat grafting fat is fat composed of adipose tissue that has been removed using a cannula and has not undergone any transformation or alteration.

[0007] MICROFAT is fat composed of adipose tissue that has been removed using a small diameter cannula and has not undergone any transformation or alteration.

[0008] NANOFAT is fat consisting of explanted adipose tissue that has been subjected to the mechanical action of a knife to liquefy it and then filtered to obtain a highly fluid, cell-rich material.

[0009] NANOFAT is also available with a kit designed for processing adipose tissue to release the stromal vascular fraction from adipose tissue cells.

[0010] In one embodiment, the fat is lipofilling fat.

[0011] In one embodiment, the fat is MICROFAT.

[0012] In one embodiment, the fat is NANOFAT.

[0013] The emulsion obtained is in the form of a composition as exemplified in Example 7, the viscoelastic properties of which are those of a gel with a G′ greater than or equal to 20 Pa.

[0014] In one embodiment, G' is greater than or equal to 30 Pa.

[0015] In one embodiment, G' is greater than or equal to 40 Pa.

[0016] The emulsion according to the invention is therefore a gelled emulsion or a gel.

[0017] In one embodiment, the gel, gelled emulsion or milk according to the invention is characterized in that the volume ratio of hydrogel / fat or fat derivative is between 0.5 / 4.5 and 2 / 3.

[0018] In one embodiment, the gel, gelled emulsion or milk according to the invention is characterized in that the volume ratio of hydrogel / fat or fat derivative is 1 / 4.

[0019] The hydrogel is composed of at least one polysaccharide selected from the group consisting of hyaluronic acid, keratan, heparin, cellulose, cellulose derivatives (particularly hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylmethylcellulose, carboxymethylcellulose), alginic acid, xanthan gum, carrageenan, chitosan, chondroitin, heparin precursors, and biologically acceptable salts thereof, alone or as a mixture.

[0020] In one embodiment, the polysaccharide is hyaluronic acid.

[0021] In one embodiment, the polysaccharide is hyaluronic acid or a salt thereof, alone or as a mixture.

[0022] In one embodiment, the polysaccharide is hyaluronic acid in the form of a sodium or potassium salt.

[0023] In one embodiment, the polysaccharide is hyaluronic acid in the form of its sodium salt.

[0024] In one embodiment, the polysaccharide is non-cross-linked hyaluronic acid or a salt thereof, alone or as a mixture.

[0025] In one embodiment, the polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture.

[0026] In one embodiment, the polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture, the cross-linking being carried out by at least one cross-linking agent.

[0027] In one embodiment, the polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture, the cross-linking being carried out by at least one bifunctional or polyfunctional cross-linking agent.

[0028] In one embodiment, the polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture, the cross-linking being carried out by at least one bifunctional cross-linking agent being butanediol diglycidyl ether (BDDE) or 1,2,7,8-diepoxyoctane.

[0029] In one embodiment, the polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture, the cross-linking being performed by BDDE.

[0030] In one embodiment, the polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture, the cross-linking being carried out by at least sodium trimetaphosphate or potassium trimetaphosphate.

[0031] When a cross-linking agent is used to cross-link a polysaccharide, and more particularly, hyaluronic acid, the cross-linking rate (x) is theoretically calculated using the following formula:

[0032]

[0033] In hyaluronic acid, the repeating unit is a disaccharide motif.

[0034] In one embodiment, the cross-linking ratio x of the cross-linked hyaluronic acid is from 0.001 to 0.5.

[0035] In one embodiment, the cross-linking ratio x of the cross-linked hyaluronic acid is from 0.01 to 0.4.

[0036] In one embodiment, the cross-linking ratio x of the cross-linked hyaluronic acid is from 0.1 to 0.3.

[0037] In one embodiment, the cross-linking ratio x of the cross-linked hyaluronic acid is 0.06.

[0038] In one embodiment, the cross-linking ratio x of the cross-linked hyaluronic acid is 0.07.

[0039] In one embodiment, the cross-linking ratio x of the cross-linked hyaluronic acid is 0.12.

[0040] In one embodiment, the polysaccharide is co-cross-linked hyaluronic acid or a salt thereof, alone or as a mixture.

[0041] In one embodiment, the polysaccharide is cross-linked or non-cross-linked hyaluronic acid or a salt thereof which has been chemically modified by substitution, alone or as a mixture.

[0042] In one embodiment, the polysaccharide is doubly cross-linked hyaluronic acid as described in patent application WO 2000 / 046253 in the name of Fermentech Medical Limited.

[0043] In one embodiment, the polysaccharide is a mixture of cross-linked and non-cross-linked hyaluronic acid or a salt thereof.

[0044] In one embodiment, the polysaccharide is a mixture of cross-linked hyaluronic acid or its salts.

[0045] In one embodiment, the polysaccharide is a mixture of cross-linked hyaluronic acid or its salts, such as described in patent application WO 2009 / 071697 in the name of the Applicant.

[0046] In one embodiment, the polysaccharide is a mixture of hyaluronic acids obtained by mixing several hyaluronic acids or salts thereof of different molecular weights before crosslinking, as described in patent application WO2004092222 in the name of Cornéal Industrie.

[0047] In one embodiment, the polysaccharide is a hyaluronic acid or a salt thereof substituted with groups conferring lipophilic or moisturizing properties, such as the substituted hyaluronic acids described in patent application FR 2983483 in the name of the Applicant. This application describes a method for simultaneously substituting and crosslinking polysaccharides via their hydroxyl functional groups in an aqueous phase, characterized in that the method comprises the following steps: (i) placing the polysaccharide in an aqueous medium, (ii) placing it in the presence of at least one substituent precursor, (iii) placing it in the presence of a crosslinking agent, and (iv) obtaining and isolating the substituted and crosslinked polysaccharide. These method steps can be perfectly implemented within the framework of the present invention.

[0048] In one embodiment, the polysaccharide is hyaluronic acid or a salt thereof grafted with glycerol, for example as described in application WO2017162676 in the name of MERZ.

[0049] In one embodiment, the molecular weight Mw of the at least one hyaluronic acid is in the range of 0.01 MDa to 5 MDa (0.01≤Mw≤5 MDa).

[0050] In one embodiment, the molecular weight Mw of the at least one hyaluronic acid is in the range of 0.1 MDa to 3.5 MDa (0.1≤Mw≤3.5 MDa).

[0051] In one embodiment, the at least one hyaluronic acid has an average molecular weight Mw in the range of 1 MDa to 3 MDa (1≤Mw≤3 MDa).

[0052] In one embodiment, the molecular weight Mw of the at least one hyaluronic acid is 1 MDa.

[0053] In one embodiment, the molecular weight Mw of the at least one hyaluronic acid is 3 MDa.

[0054] In one embodiment, the concentration of hyaluronic acid [HA] is from 2 mg / g to 50 mg / g of the total weight of the hydrogel.

[0055] In one embodiment, the concentration of hyaluronic acid [HA] is 4 mg / g to 40 mg / g of the total weight of the hydrogel.

[0056] In one embodiment, the concentration of hyaluronic acid [HA] is from 5 mg / g to 30 mg / g of the total weight of the hydrogel.

[0057] In one embodiment, the concentration of hyaluronic acid [HA] is from 10 mg / g to 30 mg / g of the total weight of the hydrogel.

[0058] In one embodiment, the concentration of hyaluronic acid [HA] is 20 mg / g of the total weight of the hydrogel.

[0059] In one embodiment, the concentration of hyaluronic acid [HA] is 14 mg / g of the total weight of the hydrogel.

[0060] In one embodiment, the concentration of hyaluronic acid [HA] is 10 mg / g of the total weight of the hydrogel.

[0061] In one embodiment, the gel, gelled emulsion or lotion further comprises at least one active ingredient selected from the group consisting of a local anesthetic, a vitamin C derivative, an anti-inflammatory agent, an antioxidant, and mixtures thereof.

[0062] In one embodiment, the gel, gelled emulsion or emulsion is free of emulsifiers, for example as described in patent application WO2011019822 in the name of JOHN HOPKINS.

[0063] In one embodiment, the gel, gelling emulsion or cream does not contain compounds that promote vascularization (angiogenesis or angiogenesis) as described in patent application US20120189708 in the name of ALLERGAN.

[0064] In one embodiment, the gel, gelling emulsion or emulsion does not contain a polymer that promotes cell viability or cell proliferation, for example, silk fibers or collagen as described in application US20180055971 in the name of ALLERGAN.

[0065] In one embodiment, the hydrogel is sterile, which means that the hydrogel has undergone a sterilization step after its preparation, which is carried out by heating, by moist heat, by gamma radiation (γ), by accelerated electron beams, or by sterile filtration (0.22 μm) in the case of hydrogels based on non-cross-linked hyaluronic acid.

[0066] In one embodiment, the sterilization step is performed by steam autoclaving.

[0067] In one embodiment, steam autoclaving is conducted at a temperature of 121°C to 134°C, for a duration appropriate to that temperature.

[0068] In one embodiment, steam autoclaving is performed at a temperature of 127°C to 130°C for a duration of 1 to 20 minutes.

[0069] In one embodiment, the sterilization value F0 is greater than 1 minute at 121°C.

[0070] In one embodiment, the sterilization step is performed by irradiation with gamma (γ) rays.

[0071] In one embodiment, the process for preparing a gel, gelled emulsion or milk according to the invention further comprises at least one step of adding at least one active ingredient.

[0072] In one embodiment, at least one active ingredient is added in powder form.

[0073] In one embodiment, at least one active ingredient is added in the form of a solution or suspension.

[0074] In one embodiment, at least one active ingredient is added in the form of a solution or suspension in a solvent or solution selected from the group consisting of water, saline solution, such as a phosphate buffered solution, such as PBS.

[0075] In one embodiment, at least one active ingredient is added to the hyaluronic acid.

[0076] In one embodiment, at least one active ingredient is added at a later stage during the steps of preparing the gel, gelled emulsion or milk according to the invention.

[0077] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one active ingredient selected from the group consisting of local anesthetics, microbe C derivatives, anti-inflammatory agents, antioxidants and mixtures thereof.

[0078] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic.

[0079] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of 0.1% to 5% relative to the total mass of the emulsion.

[0080] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of 0.1% to 4% relative to the total mass of the emulsion.

[0081] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of 0.1% to 2% relative to the total mass of the emulsion.

[0082] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of 0.1% to 1% relative to the total mass of the emulsion.

[0083] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of 0.1% to 0.5% relative to the total mass of the emulsion.

[0084] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic to obtain a local anesthetic concentration of about 0.3% relative to the total mass of the emulsion.

[0085] In one embodiment, the local anesthetic is selected from the group of aminoesters.

[0086] In one embodiment, the amino ester is selected from procaine, benzocaine, chloroprocaine and tetracaine in base or salt form (eg, hydrochloride form).

[0087] In one embodiment, the local anesthetic is selected from the group of aminoamides.

[0088] In one embodiment, the aminoamide is selected from lidocaine, mepivacaine, prilocaine, articaine, atocaine, bupivacaine, etidocaine, and ropivacaine in base or salt form (eg, hydrochloride form).

[0089] In one embodiment, the local anesthetic is selected from the group of amino ethers.

[0090] In one embodiment, the aminoether is selected from diaminocaine and pramoxine in base or salt form (eg, in hydrochloride or cyclamate form).

[0091] In one embodiment, the amino ether is selected from lidocaine, mepivacaine, and salts and isolated isomers thereof.

[0092] In one embodiment, the aminoether is lidocaine.

[0093] In one embodiment, the aminoether is lidocaine or a pharmaceutically acceptable salt thereof.

[0094] In one embodiment, the amino ether is lidocaine hydrochloride.

[0095] In one embodiment, the aminoether is mepivacaine.

[0096] In one embodiment, the aminoether is mepivacaine or a pharmaceutically acceptable salt thereof.

[0097] In one embodiment, the amino ether is selected from racemic mepivacaine hydrochloride, (r)-mepivacaine hydrochloride, (s)-mepivacaine hydrochloride, (r)-mepivacaine and (s)-mepivacaine, or a pharmaceutically acceptable salt thereof.

[0098] In one embodiment, the amino ether is mepivacaine hydrochloride.

[0099] In one embodiment, the amino ether is (r)-mepivacaine hydrochloride.

[0100] In one embodiment, the amino ether is (S)-mepivacaine hydrochloride.

[0101] In one embodiment, the amino ether is racemic mepivacaine hydrochloride.

[0102] In one embodiment, the amino ether is (r)-mepivacaine.

[0103] In one embodiment, the amino ether is (s)-mepivacaine.

[0104] In one embodiment, the amino ether is racemic mepivacaine.

[0105] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one aminoether local anesthetic selected from the group consisting of lidocaine, mepivacaine, and mixtures thereof.

[0106] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, ie lidocaine.

[0107] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, i.e. lidocaine, to obtain a lidocaine concentration ranging from 0.1% to 5% relative to the total mass of the emulsion.

[0108] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, i.e. lidocaine, to obtain a lidocaine concentration ranging from 0.1% to 4% relative to the total mass of the emulsion.

[0109] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, i.e. lidocaine, to obtain a lidocaine concentration ranging from 0.1% to 2% relative to the total mass of the emulsion.

[0110] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, i.e. lidocaine, to obtain a lidocaine concentration ranging from 0.1% to 1% relative to the total mass of the emulsion.

[0111] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, i.e. lidocaine, to obtain a lidocaine concentration ranging from 0.1% to 0.5% relative to the total mass of the emulsion.

[0112] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, i.e. lidocaine, to obtain a local anesthetic concentration of about 0.3% relative to the total mass of the emulsion.

[0113] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, ie mepivacaine.

[0114] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, namely mepivacaine, to obtain a mepivacaine concentration ranging from 0.1% to 5% relative to the total mass of the emulsion.

[0115] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, namely mepivacaine, to obtain a mepivacaine concentration ranging from 0.1% to 4% relative to the total mass of the emulsion.

[0116] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, namely mepivacaine, to obtain a mepivacaine concentration ranging from 0.1% to 2% relative to the total mass of the emulsion.

[0117] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, namely mepivacaine, to obtain a mepivacaine concentration ranging from 0.1% to 1% relative to the total mass of the emulsion.

[0118] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, namely mepivacaine, to obtain a mepivacaine concentration ranging from 0.1% to 0.5% relative to the total mass of the emulsion.

[0119] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic, i.e. mepivacaine, to obtain a local anesthetic concentration of about 0.3% relative to the total mass of the gel, gelled emulsion or emulsion.

[0120] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic (ie dyclonine in base or salt form, such as the hydrochloride form).

[0121] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one local anesthetic selected from the group consisting of chlorobutanol, guanifecarol and polidocanol.

[0122] In one embodiment, the local anesthetic is chlorobutanol.

[0123] In one embodiment, the local anesthetic is guanfilcarnitine.

[0124] In one embodiment, the local anesthetic is polidocanol.

[0125] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent.

[0126] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from steroidal anti-inflammatory drugs and non-steroidal anti-inflammatory drugs.

[0127] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from non-steroidal anti-inflammatory drugs.

[0128] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from the group comprising salicylated anti-inflammatory agents, propionic acid derivatives, indole derivatives, pyrazole derivatives, oxicams and coxibs.

[0129] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from the group comprising diclofenac, nimésulfide, niflumic acid, mefenamic acid and nabumetone, alone or as a mixture.

[0130] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one salicylated anti-inflammatory agent selected from the group comprising diflunisal, benolate and aspirin, alone or as a mixture.

[0131] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from the group of propionic acid derivatives comprising, alone or as a mixture, amiprofen, ketoprofen, ibuprofen, naproxen, flurbiprofen and tiaprofenic acid.

[0132] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from the group of indole derivatives comprising, alone or as a mixture, indomethacin, sulindac and etodolac.

[0133] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from the group comprising pyrazole derivatives, in particular phenylbutazone.

[0134] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from the group of oxicams comprising, alone or as a mixture, piroxicam, tenoxicam and meloxicam.

[0135] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from the group of coxibs comprising, alone or as a mixture, celecoxib, etoricoxib and rofecoxib.

[0136] In one embodiment, the concentration of the nonsteroidal anti-inflammatory drug in the gel, gelled emulsion or cream according to the invention is from 0.01 mg / g to 2000 mg / g.

[0137] In one embodiment, the concentration of the nonsteroidal anti-inflammatory drug in the gel, gelled emulsion or cream according to the invention is from 0.1 mg / g to 1000 mg / g.

[0138] In one embodiment, the concentration of the nonsteroidal anti-inflammatory drug in the gel, gelled emulsion or cream according to the invention is from 0.5 mg / g to 500 mg / g.

[0139] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one steroidal anti-inflammatory drug.

[0140] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one steroidal anti-inflammatory drug selected from the group comprising dexamethasone, prednisolone, corticosterone, budesonide, sulfasalazine, mesalazine, cetirizine, diphenhydramine, antipyrine, methyl salicylate, loratadine, thymol, carvacrol, bisabolol, allantoin, eucalyptol, phenazone (antipyrine), isopropyl antipyrine, alone or as a mixture.

[0141] In one embodiment, the concentration of the steroidal anti-inflammatory agent in the gel, gelled emulsion or cream according to the invention is from 0.01 mg / g to 2000 mg / g.

[0142] In one embodiment, the concentration of the steroidal anti-inflammatory agent in the gel, gelled emulsion or cream according to the invention is from 0.1 mg / g to 1000 mg / g.

[0143] In one embodiment, the concentration of the steroidal anti-inflammatory agent in the gel, gelled emulsion or cream according to the invention is from 0.5 mg / g to 500 mg / g.

[0144] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from sucrose octasulfate and salts thereof.

[0145] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory agent selected from sucrose octasulfate and its sodium and potassium salts.

[0146] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory water-soluble salt of sucrose octasulfate selected from the group consisting of alkali metal salts, alkaline earth metal salts, silver salts, ammonium salts, amino acid salts.

[0147] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory water-soluble salt of sucrose octasulfate selected from alkali metal salts or alkaline earth metal salts.

[0148] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-inflammatory water-soluble sucrose octasulfate salt selected from the following: sodium salt of sucrose octasulfate or potassium salt of sucrose octasulfate.

[0149] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antimicrobial agent.

[0150] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antimicrobial agent selected from the group comprising gentamicin, silver sulfadiazine, metronidazole, fusidic acid, bacitracin, eosin, povidone iodine, copper gluconate, zinc gluconate, manganese gluconate, or salts thereof, alone or as a mixture.

[0151] In one embodiment, the concentration of the antimicrobial agent in the gel, gelled emulsion or cream according to the invention is from 0.1 mg / g to 200 mg / g.

[0152] In one embodiment, the concentration of the antimicrobial agent in the gel, gelled emulsion or cream according to the invention is from 0.5 mg / g to 100 mg / g.

[0153] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one glycoside or glycoside derivative.

[0154] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the present invention further comprises at least one step of adding at least one glycoside or glycoside derivative selected from the group comprising: D-pyranose glucose, 1,4-glycoside, esculin, hesperidin, diosmin, arbutin, artoside or aloin, alone or in mixture.

[0155] In one embodiment, the concentration of glycoside in the gel, gelled emulsion or emulsion according to the invention is from 0.1 mg / g to 200 mg / g.

[0156] In one embodiment, the concentration of glycoside in the gel, gelled emulsion or emulsion according to the invention is from 0.5 mg / g to 100 mg / g.

[0157] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent.

[0158] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent selected from the major elements.

[0159] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the present invention further comprises at least one step of adding at least one macroelement selected from the group comprising iron gluconate, calcium gluconate, copper gluconate, zinc gluconate, manganese gluconate, magnesium gluconate or potassium gluconate, trimethylsilanol, trimethylsilanolate, potassium trimethylsilanolate, methylsilanol mannuronate, sodium monoethyltrisilanol o-hydroxybenzoate, alone or as a mixture.

[0160] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent selected from essential amino acids.

[0161] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one essential amino acid selected from the group comprising isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine, alone or as a mixture.

[0162] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent chosen from semi-essential amino acids.

[0163] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one semi-essential amino acid selected from the group comprising arginine and histidine, alone or as a mixture.

[0164] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent selected from non-essential amino acids.

[0165] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one non-essential amino acid selected from the group comprising alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, tyrosine, alone or as a mixture.

[0166] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent selected from vitamins.

[0167] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one vitamin selected from the group consisting of retinol, thiamine, riboflavin, niacinamide, adenine, calcium pantothenate, pyridoxine, inositol, biotin, folic acid, para-aminobenzoic acid, cobalamin, vitamin C, choline chloride, alone or as a mixture.

[0168] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one tissue moisturizing agent or tissue regenerating agent selected from nucleic acids.

[0169] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one nucleic acid selected from the group consisting of deoxyadenosine, deoxycytidine, deoxyguanosine, deoxythymidine, methylcytosine, alone or as a mixture.

[0170] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent selected from coenzymes.

[0171] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one coenzyme selected from the following alone or as a mixture: thiamine pyrophosphate, coenzyme A, FAD, NAD, NADP, UTP.

[0172] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the present invention further comprises at least one step of adding at least one moisturizing agent or tissue regenerating agent selected from the group consisting of deoxythymidine, glutathione, sodium pyruvate, lipoic acid and putrescine, alone or as a mixture.

[0173] In one embodiment, the concentration of the tissue moisturizing or rejuvenating agent in the gel, gelled emulsion or milk according to the invention is from 0.01 mg / g to 500 mg / g.

[0174] In one embodiment, the concentration of the tissue moisturizing or rejuvenating agent in the gel, gelled emulsion or milk according to the invention is from 0.1 mg / g to 200 mg / g.

[0175] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant.

[0176] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group of polyols.

[0177] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol selected from the group consisting of mannitol, sorbitol, propylene glycol, xylitol, glycerol, maltitol, lactitol and erythritol.

[0178] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol selected from the group consisting of mannitol, sorbitol, maltitol and glycerol, alone or as a mixture.

[0179] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol selected from the group consisting of mannitol, sorbitol and maltitol, and salts thereof.

[0180] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of 0.1 to 50 mg / ml relative to the total mass of the emulsion.

[0181] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of 5 to 40 mg / ml relative to the total mass of the emulsion.

[0182] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of 10 to 40 mg / ml relative to the total mass of the emulsion.

[0183] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of 20 to 40 mg / ml relative to the total mass of the emulsion.

[0184] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol to obtain a polyol concentration of 30 to 40 mg / ml relative to the total mass of the emulsion.

[0185] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol, namely mannitol.

[0186] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of 5 to 40 mg / ml relative to the total mass of the emulsion.

[0187] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of 10 to 40 mg / ml relative to the total mass of the emulsion.

[0188] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of 20 to 40 mg / ml relative to the total mass of the emulsion.

[0189] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding mannitol to obtain a mannitol concentration of 30 to 40 mg / ml relative to the total mass of the emulsion.

[0190] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol, namely sorbitol.

[0191] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of 5 to 40 mg / ml relative to the total mass of the emulsion.

[0192] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of 10 to 40 mg / ml relative to the total mass of the emulsion.

[0193] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of 20 to 40 mg / ml relative to the total mass of the emulsion.

[0194] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding sorbitol to obtain a sorbitol concentration of 30 to 40 mg / ml relative to the total mass of the emulsion.

[0195] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol, namely maltitol.

[0196] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one polyol, ie glycerol.

[0197] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding a mixture of mannitol and sorbitol.

[0198] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group of vitamin C derivatives.

[0199] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group of vitamin C derivatives comprising magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbic acid-2-glucoside, and mixtures thereof.

[0200] In one embodiment, the at least one vitamin C derivative is magnesium ascorbyl phosphate.

[0201] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group of tocopherol and vitamin E derivatives.

[0202] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group consisting of carotenoids and retinoids and derivatives thereof.

[0203] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group consisting of carotenoids and retinoids and derivatives thereof comprising retinol, retinoic acid, retinal, retinol esters and carotene.

[0204] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group of tripeptide mimetics.

[0205] In one embodiment, the tripeptide mimetic is glutathione.

[0206] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group comprising different forms of Coenzyme Q10, ubiquinone or ubiquinol.

[0207] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one vitamin.

[0208] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one vitamin selected from the group comprising retinol, thiamine, riboflavin, niacinamide, dexpanthenol, pyridoxine, ascorbic acid, ergocalciferol, tocopherol, biotin and folic acid, alone or as a mixture.

[0209] In one embodiment, the vitamin concentration in the emulsion according to the invention is from 0.01 mg / g to 200 mg / g.

[0210] In one embodiment, the vitamin concentration in the emulsion according to the invention is from 0.01 mg / g to 100 mg / g.

[0211] In one embodiment, the vitamin concentration in the emulsion according to the invention is from 0.5 mg / g to 50 mg / g.

[0212] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one amino acid.

[0213] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one amino acid selected from the group consisting of essential amino acids, semi-essential amino acids and non-essential amino acids, alone or as a mixture.

[0214] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one amino acid selected from the group of essential amino acids.

[0215] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one essential amino acid selected from the group comprising isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine, alone or as a mixture.

[0216] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one amino acid selected from the group of semi-essential amino acids.

[0217] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one semi-essential amino acid selected from the group comprising arginine and histidine, alone or as a mixture.

[0218] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one amino acid selected from the group of non-essential amino acids.

[0219] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one non-essential amino acid selected from the group comprising alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, tyrosine, alone or as a mixture.

[0220] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one amino acid selected from the group comprising hydroxyproline, taurine and ornithine, alone or as a mixture.

[0221] In one embodiment, the concentration of amino acids in the emulsion according to the invention is from 0.01 mg / g to 150 mg / g.

[0222] In one embodiment, the concentration of amino acids in the emulsion according to the invention is from 0.01 mg / g to 100 mg / g.

[0223] In one embodiment, the concentration of amino acids in the emulsion according to the invention is from 0.5 mg / g to 50 mg / g.

[0224] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one vasoconstrictor.

[0225] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one vasoconstrictor selected from the group comprising naphazoline, epinephrine, methoxyamine, methylnorepinephrine, norepinephrine, oxymetazoline, phenylephrine, pseudoephedrine, synephrine, cirazoline and xylometazoline.

[0226] In one embodiment, the concentration of the vasoconstrictor in the emulsion according to the invention is from 0.01 mg / g to 3 mg / g.

[0227] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one vasodilator.

[0228] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one vasodilator selected from the group comprising adenosine, nicotinic acid, minoxidil and diazoxide, alone or as a mixture.

[0229] In one embodiment, the concentration of the vasodilator in the gel, gelled emulsion or emulsion according to the invention is from 0.01 mg / g to 10 mg / g.

[0230] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-hemorrhagic or hemostatic agent.

[0231] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one anti-hemorrhagic or hemostatic agent selected from the group comprising aminocaproic acid or tranexamic acid, alone or as a mixture.

[0232] In one embodiment, the concentration of the anti-hemorrhagic or hemostatic agent in the gel, gelled emulsion or emulsion according to the invention is from 0.01 mg / g to 5 mg / g.

[0233] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant and at least one local anesthetic.

[0234] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one antioxidant selected from the group of polyols and at least one local anesthetic selected from the group of aminoamides.

[0235] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel 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 regeneration agent.

[0236] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel 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 regeneration agent.

[0237] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel 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 regeneration agent.

[0238] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one active ingredient chosen from heat-sensitive active ingredients.

[0239] In one embodiment, at least one heat-sensitive active ingredient is added during the preparation of the gel, gelled emulsion or emulsion according to the invention, ie during the step of mixing the hydrogel with the fat or fat derivative.

[0240] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding a so-called thermosensitive active ingredient of natural origin.

[0241] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention also comprises at least one step of adding a so-called thermosensitive active ingredient of synthetic origin.

[0242] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one thermosensitive active ingredient selected from the group consisting of peptides, hormones, proteins, growth factors, antibodies and vitamins, alone or as a mixture.

[0243] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one thermosensitive active ingredient selected from peptides.

[0244] In one embodiment, the added heat-sensitive active ingredient is a peptide.

[0245] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one thermosensitive active ingredient selected from hormones.

[0246] In one embodiment, the added heat-sensitive active ingredient is a hormone.

[0247] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one heat-sensitive active ingredient chosen from proteins.

[0248] In one embodiment, the added heat-sensitive active ingredient is a protein.

[0249] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one thermosensitive active ingredient chosen from growth factors.

[0250] In one embodiment, the added thermosensitive active ingredient is a growth factor.

[0251] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one thermosensitive active ingredient selected from antibodies.

[0252] In one embodiment, the added heat-sensitive active ingredient is an antibody.

[0253] In one embodiment, the process for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one heat-sensitive active ingredient chosen from vitamins.

[0254] In one embodiment, the vitamins are selected from retinol, thiamine, riboflavin, niacinamide, dexpanthenol, pyridoxine, ascorbic acid, ergocalciferol, tocopherol, biotin and folic acid, alone or as a mixture.

[0255] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one auxiliary ingredient for mesotherapy selected from tissue inducing agents.

[0256] In one embodiment, the auxiliary ingredient added for mesodermal therapy is a tissue inducing agent.

[0257] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the present invention further comprises at least one step of adding at least one auxiliary ingredient for mesotherapy selected from calcium hydroxyapatite, L-polylactic acid (PLLA), polycaprolactone, polymethyl methacrylate (PMMA) and / or polyalkylamide. In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the present invention further comprises at least one step of adding at least one carrier for a tissue inducer.

[0258] In one embodiment, the method for preparing an emulsion, gelled emulsion or gel according to the invention further comprises at least one step of adding at least one carrier for the tissue inducing agent selected from glycerol, carboxymethylcellulose, glycerol, polyethylene glycol or even dextran.

[0259] Target applications are more particularly the following pathologies or treatments:

[0260] - Aesthetic injections for the face: for mesotherapy, skin rejuvenation, filling of wrinkles and fine lines, skin blemishes and skin imperfections, or volume augmentation (zygomatic bone, chin, lips or any other part of the face, head or scalp);

[0261] - Enhanced tissue trophism; increased microvascularization, type II collagen, and tissue thickness;

[0262] - Body volume injections: breast and buttocks augmentation, G-spot enlargement, vaginoplasty, lip reconstruction, penis enlargement; or any area of ​​the body that requires fat volume or skin nutritional enhancement: hands and limbs, heels and support areas, buttocks and private areas;

[0263] - Treatment of osteoarthritis, injections into the joints to replace or supplement defective synovial fluid;

[0264] - Periurethral injections for the treatment of urinary incontinence due to sphincter insufficiency;

[0265] - Postoperative injection to prevent adhesions, especially peritoneal adhesions;

[0266] -Injections after presbyopia surgery using laser scleral incisions;

[0267] - Injection into the vitreous cavity;

[0268] - Injections during cataract surgery;

[0269] - Injections into the genitals;

[0270] -For injection into interstitial spaces.

[0271] More particularly, in cosmetic surgery, the emulsion according to the invention can be used, on the basis of its viscoelastic and remanent magnetic properties:

[0272] - To enhance skin hydration and quality through mesodermal treatment of the face, neck, décolleté or hands. In this case, a 22G to 32G diameter and usually 1 / 8" to 1 / 2" in length is used. 1 The product can be injected with a needle of varying sizes from 1 / 2". The composition can be injected manually or using an automatic device (eg, an injection pen and / or an injection gun).

[0273] - For tissue rejuvenation. In this case, a 22-gauge to 32-gauge diameter and usually 1 / 8” to 1 / 2” needles are used to inject the product.

[0274] - Used to fill fine, medium or deep wrinkles and uses small diameter needles (mainly 27G to 30G, usually 1 / 4 in length) 1 / 2”) for injection;

[0275] - as a bulking agent, where the injection is through a larger diameter (e.g. 25G to 27G) and longer (e.g. 30mm to 40mm) needle; or primarily through a cannula 40mm to 70mm in length and 22G to 25G in diameter; in this case, its cohesive nature will ensure that it is retained at the injection site.

[0276] For example, the gels, gelled emulsions or emulsions according to the invention also find important application in joint surgery and in dental surgery for filling periodontal pockets.

[0277] These few examples of uses are by no means limiting, the gel, gelled emulsion or milk according to the invention is more broadly intended for use in:

[0278] - filling volume;

[0279] - Create spaces between certain tissues;

[0280] - Replacement of insufficient physiological fluids;

[0281] -Reshape any body area.

[0282] The invention also relates to a method for preparing a gel, gelled emulsion or milk according to the invention, characterised in that the method comprises the following steps:

[0283] a) providing fat or fat derivatives,

[0284] b) providing a hydrogel,

[0285] c) aseptically mixing the hydrogel with fat or a fat derivative,

[0286] d) emulsifying the mixture until an emulsion, gelled emulsion or homogeneous gel is obtained.

[0287] In one embodiment, the hydrogel comprises an active ingredient as defined above.

[0288] In one embodiment, there is provided an active ingredient that is introduced upon mixing the hydrogel and the fat or fat derivative.

[0289] The fat, fat derivative, hydrogel and active ingredient are as defined above.

[0290] In various embodiments of the present invention, gels, gelling emulsions or emulsions comprising different hydrogels, different fat products or products derived from fat can be injected into the patient's body at different anatomical depths, in different body regions, and at different concentrations or dilutions. These different compositions and injection methods are adjusted according to the area to be treated and the different needs for remodeling or enhancing the nutritional properties of the treatment area. Therefore, different gels, gelling emulsions or emulsions can be used simultaneously or successively for the same area or different areas of the body.

[0291] The present invention makes it possible to significantly enhance the rheology of lipofilling fat by making it more suitable for injection. The gel, gelled emulsion or milk obtained is stable and has a consistency close to or equivalent to mayonnaise.

[0292] Gels, gelled emulsions or creams have a high level of extensibility, enabling them to be injected using very small diameter cannulas and allowing the practitioner to inject with extreme precision, as well as limiting adverse effects that are quite common with fat injections for liposuction alone.

[0293] The use of the emulsion, gelled emulsion or gel according to the invention makes it possible to significantly reduce the appearance of postoperative bruising compared to fat injections for lipofilling alone.

[0294] Additionally, this malleability makes the procedure easier for the surgeon and allows for a smoother procedure due to the good injectability of the emulsion.

[0295] Finally, this malleability allows surgeons to reshape different areas of the body. Once it is injected, the shape of the implanted area or implant can be modified. These post-injection modifications make it more desirable to achieve the desired effect.

[0296] The injection of the emulsion, gelled emulsion or gel according to the invention makes it possible to obtain a visible effect on the skin, such as, for example, an improvement in the radiance or a remodelling effect of the skin.

[0297] The visible effects on the skin remain noticeable for at least 3 months after injection.

[0298] The visible effects on the skin remain evident for at least 6 months after injection.

[0299] The visible effects on the skin remain evident for at least 12 months after injection.

[0300] The visible effects on the skin remain evident for at least 18 months after injection.

[0301] The invention also relates to a kit for preparing an emulsion, gelled emulsion or gel of fat or a fat derivative and hyaluronic acid, comprising a cartridge (4) and at least two syringes.

[0302] In one embodiment of the kit, the cartridge (4) comprises at least one hydrogel.

[0303] In one embodiment, the kit comprises at least 3 syringes.

[0304] In one embodiment, the kit comprises at least 4 syringes.

[0305] In one embodiment, the kit comprises at least 10 syringes.

[0306] Kit 1: Syringes 1 and 2 + cartridge 4 filled with hyaluronic acid.

[0307] Syringe 1 (medium volume syringe) is empty or filled with adipose tissue; barrel 4 contains hyaluronic acid gel (cross-linked or non-cross-linked); and syringe 2 (large volume syringe) is empty and has a capacity equal to the capacity of syringe 1 and barrel 4 combined (V1+V4).

[0308] 1. Collect fat for liposuction using Syringe 1 or previously prepared MICROFAT or NANOFAT (medium size syringe).

[0309] 2. Take out the barrel 4 pre-filled with hyaluronic acid and connect the syringe 1 to the barrel 4 using Luer-Lock connectors 1a and 4a.

[0310] 3. Add syringe 2 (large volume syringe V1 + V4) to the second tip 4-b of barrel 4 and operate the plungers 1b and 2b of both syringes 1 and 2 using back and forth movement to create an emulsion between the lipofilling fat and the hyaluronic acid gel.

[0311] 4. After several back and forth movements (at least 5 movements), completely draw up the emulsion into Syringe 2 (large volume syringe).

[0312] 5. Disconnect the syringe 2 from the barrel and prepare to inject the gel, gelled emulsion or emulsion contained in the syringe 2.

[0313] 6. A cannula is mounted on the tip 2a of the syringe 2 to perform the injection. The choice of these cannulas is at the discretion of the surgeon depending on the area to be treated.

[0314] An optional step may be performed to incorporate the active ingredient into the gel, gelled emulsion or emulsion of hyaluronic acid and lipofilling fat. These new steps may be combined at two different times.

[0315] -Implementation before step 3:

[0316] a) After several back and forth movements (at least 5 movements), completely draw up the gel, gelled emulsion or emulsion into Syringe 2 (large volume syringe).

[0317] b) Disconnecting the syringe 1 from the tip 4a of the barrel and connecting the syringe 5 containing the active ingredient to the tip 4b on the same barrel.

[0318] c) Empty the contents of syringe 5 into the barrel and then operate the plungers 2b and 5b of syringes 2 and 5 to mix the gel, gelled emulsion or cream containing the active ingredient.

[0319] d) Draw the mixture completely into syringe 2

[0320] or

[0321] - Implementation after step 4:

[0322] a) Disconnect the syringe 2 from the barrel.

[0323] b) Connecting together the syringe 2 containing the gel, gelled emulsion or cream of hyaluronic acid and fat for lipofilling and the syringe 5 containing the active ingredient via a double Luer lock connector connected to the tips 2a and 5a of the two syringes respectively.

[0324] c) Mix the gel, gelled emulsion or cream and the active ingredient by operating the respective plungers 2b and 5b of the syringes in a back and forth motion (at least 5 movements).

[0325] d) The emulsion mixed with the active ingredient is completely introduced into the syringe 2.

[0326] e) Disconnecting the syringe 2 and preparing to inject the gel, gelled emulsion or emulsion contained in the syringe 2.

[0327] Kit 2: Syringes 1, 2 and 3 + Cartridge 4

[0328] Syringe 1 (medium volume syringe) is used to collect fat for liposuction or transformed fat; syringe 3 (small volume syringe) contains hyaluronic acid gel (cross-linked or non-cross-linked); barrel 4 and syringe 2 (large volume syringe) are empty.

[0329] 1. Collect fat for liposuction using Syringe 1 (medium-sized syringe).

[0330] 2. Connect the syringe 1 to the empty barrel 4 using connectors 1a and 4a.

[0331] 3. Connect the syringe 3 (small syringe) containing HA gel to the empty cartridge 4 using connectors 3a and 4b.

[0332] 4. Fill the empty barrel 4 with the contents of syringe 3 (HA gel).

[0333] 5. Disconnect syringe 3 from tip 4b and connect syringe 2 (larger syringe V1 + V4) to tip 4b using connector 2a.

[0334] 6. Make a back and forth movement on the plungers 1b and 2b of the two syringes 1 and 2 to produce an emulsion (at least 5 movements),

[0335] 7. Completely fill Syringe 2 with the contents of Syringe 1 and Barrel 4.

[0336] 8. Disconnect the syringe 2 from the barrel and prepare to inject the gel, gelled emulsion or emulsion contained in the syringe 2.

[0337] 9. A cannula is mounted on the tip 2a of the syringe 2 to perform the injection. The choice of these cannulas is at the discretion of the surgeon depending on the area to be treated.

[0338] In one embodiment, a syringe 5 may be added to kit 1 or kit 2, for example in order to incorporate an active ingredient as defined above.

[0339] An optional step may be performed to incorporate the active ingredient into the gel, gelled emulsion or emulsion of hyaluronic acid and lipofilling fat. These new steps may be combined at two different times.

[0340] - Implementation after step 6:

[0341] a) Completely fill syringe 3 with the contents of syringe 1 and barrel 4.

[0342] b) Disconnect syringe 3 and connect syringe 5 via tip 5a in position on tip 4b of the barrel.

[0343] c) Empty the contents of syringe 5 into barrel 4.

[0344] d) operating the plungers 2b and 5b of the syringes 2 and 5 to move back and forth (at least 5 times) to mix the gel, gelled emulsion or milk and the active ingredient.

[0345] e) Completely fill syringe 2 with the contents of syringe 5 and barrel 4.

[0346] or

[0347] - Implementation after step 8:

[0348] a) Disconnect the syringe 2 from the barrel.

[0349] b) Connecting together the syringe 2 containing the gel, gelled emulsion or cream of hyaluronic acid and fat for lipofilling and the syringe 5 containing the active ingredient via a double Luer lock connector connected to the tips 2a and 5a of the two syringes respectively.

[0350] c) Mix the gel, gelled emulsion or cream and the active ingredient by operating the respective plungers 2b and 5b of the syringes in a back and forth motion (at least 5 movements).

[0351] d) Completely draw the gel, gelled emulsion or milk mixed with the active ingredient into syringe 2.

[0352] e) Disconnecting the syringe 2 and preparing to inject the emulsion contained in the syringe 2.

[0353] Kit 3: two 20 ml syringes (2), two 10 ml syringes (1), ten 1 ml syringes (3), all with or without Luer lock, and a cartridge (4).

[0354] In one embodiment, two 20 ml syringes are used to collect fat from the patient, two 10 ml syringes contain pure fat for liposuction or pure transformed fat (MICROFAT or NANOFAT), a 1 ml syringe is filled with different compositions to be injected into the patient, and a barrel (4) contains a gel for forming an emulsion.

[0355] 1. Collect fat from the patient using two 20 ml syringes.

[0356] 2. Wash the fat contained in two 20 ml syringes and then decant or centrifuge to separate the different components and keep only the pure fat.

[0357] 3. The fat phase is then introduced into one of two 10 ml syringes.

[0358] 4. Optionally, two 1 ml syringes can be used to collect 2 ml of pure fat.

[0359] 5. Use two 10 ml syringes to convert pure fat into lipofilling fat or into converted fat.

[0360] 6. Both syringes are connected via their Luer lock tips to the fat preparation device to obtain fat for lipofilling or converted fat.

[0361] 7. Once the liposuction fat or converted fat is obtained, introduce it in portions into four 1 ml syringes.

[0362] 8. Then connect a 10 ml syringe containing the remaining lipofilling fat or converted fat to the barrel (4) containing the gel via the Luer lock tip and tip (4a) and connect a second 10 ml syringe to the barrel on the second tip (4b).

[0363] 9. Aspirate the contents of the cartridge into the syringe containing the lipofilling fat or transformed fat and create an emulsion by moving it back and forth between two 10 ml syringes by operating their plungers (at least 5 movements).

[0364] 10. After the emulsion is formed, draw it completely into a 10 ml syringe.

[0365] 11. Four 1 ml syringes are then connected sequentially to the 10 ml syringe and filled with the emulsion to provide four syringes containing the gel, gelled emulsion or emulsion to be injected.

[0366] 12. After these various steps, the practitioner has two syringes containing pure fat,

[0367] 4 syringes containing fat for liposuction or transformed fat and 4 syringes containing a gel, gelled emulsion or emulsion according to the invention.

[0368] 13. A cannula is mounted on each of the syringes shown in point 12 using a Luer lock tip to perform the injection of the different compositions previously defined. The choice of these cannulas is at the discretion of the surgeon depending on the area to be treated.

[0369] Description of cartridges and different emulsification devices

[0370] In one embodiment, the cartridge is empty and it allows mixing of the lipofilling fat with a gel consisting of at least one polysaccharide (free or cross-linked), alone or in a mixture, to form a gel, gelled emulsion or milk according to the invention.

[0371] In one embodiment, the cartridge contains only a gel consisting of at least one polysaccharide (free and / or cross-linked), alone and / or in mixture, and which allows mixing the lipofilling fat with this gel to form a gel, gelled emulsion or emulsion according to the invention.

[0372] In one embodiment, the cartridge allows static mixing of the lipofilling fat with a gel consisting of at least one polysaccharide (free or cross-linked), alone or in a mixture, to form a gel, gelled emulsion or milk according to the invention.

[0373] In one embodiment, the cylinder for static mixing of fat for fat filling consists of two tips (6), the mixing cylinder (I) mixing the gel through the presence of two parallel planes (7c) and (8c), one of which has a single central hole (7d) and the second has multiple holes (8d) on the periphery.

[0374] In one embodiment, the cartridge for static mixing of fat and gel for lipofilling consists of two tips (9) and (10), also forming the body of a mixing cartridge (II), in which a mixing crossbar (11) is incorporated.

[0375] In one embodiment, a mixing barrel (III) for static mixing of fat and gel for fat filling consists of a tip (12), a connector (14) enclosing a mixing cross (15), and a body (13) comprising a vertical plane (13c) having a plurality of holes (13d).

[0376] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 0.5 ml to 10 ml.

[0377] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 0.5 ml.

[0378] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 1 ml.

[0379] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 2 ml.

[0380] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 3 ml.

[0381] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 4 ml.

[0382] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 5 ml.

[0383] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 6 ml.

[0384] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 7 ml.

[0385] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 8 ml.

[0386] In one embodiment, the capacity of the cartridge for static mixing of fat and gel for liposuction is 9 ml.

[0387] In one embodiment, the capacity of the cartridge used for static mixing of fat and gel for liposuction is 10 ml.

[0388] In one embodiment, the diameter of the cylinder used for static mixing of fat and gel for lipofilling is 8 mm to 30 mm.

[0389] In one embodiment, the diameter of the cylinder used for static mixing of fat and gel for lipofilling is 8 mm.

[0390] In one embodiment, the diameter of the cylinder used for static mixing of fat and gel for lipofilling is 10 mm.

[0391] In one embodiment, the diameter of the cylinder used for static mixing of fat and gel for lipofilling is 15 mm.

[0392] In one embodiment, the diameter of the cylinder used for static mixing of fat and gel for lipofilling is 20 mm.

[0393] In one embodiment, the diameter of the cylinder used for static mixing of fat and gel for liposuction is 25 mm.

[0394] In one embodiment, the diameter of the cylinder used for static mixing of fat and gel for lipofilling is 30 mm.

[0395] In one embodiment, the length of the cylinder used for static mixing of fat and gel for lipofilling is 45 mm to 100 mm.

[0396] In one embodiment, the length of the barrel used for static mixing of fat and gel for liposuction is between 45 mm.

[0397] In one embodiment, the length of the cylinder used for static mixing of fat and gel for liposuction is between 50 mm.

[0398] In one embodiment, the length of the barrel used for static mixing of fat and gel for liposuction is between 55 mm.

[0399] In one embodiment, the length of the cylinder used for static mixing of fat and gel for liposuction is between 60 mm.

[0400] In one embodiment, the length of the barrel used for static mixing of fat and gel for liposuction is between 65 mm.

[0401] In one embodiment, the length of the cylinder used for static mixing of fat and gel for liposuction is between 70 mm.

[0402] In one embodiment, the length of the barrel used for static mixing of fat and gel for liposuction is between 75 mm.

[0403] In one embodiment, the length of the cylinder used for static mixing of fat and gel for liposuction is between 80 mm.

[0404] In one embodiment, the length of the barrel used for static mixing of fat and gel for liposuction is between 85 mm.

[0405] In one embodiment, the length of the cylinder used for static mixing of fat and gel for liposuction is between 90 mm.

[0406] In one embodiment, the length of the barrel used for static mixing of fat and gel for liposuction is between 95 mm.

[0407] In one embodiment, the length of the cylinder used for static mixing of fat and gel for liposuction is between 100 mm. BRIEF DESCRIPTION OF THE DRAWINGS

[0408] Figure 1 A cartridge (4) and four syringes (1), (2), (3) and (5) are shown.

[0409] Figure 2 Shown is an overall view of an assembled mixing cartridge (I) consisting of two identical tips (6), a single-hole body (7), and a perforated body (8). The different parts constituting the mixing cartridge (I) are assembled to each other.

[0410] Figure 3 A cross-sectional view of the assembled mixing cartridge (I) is shown, showing components (7) and (8) fitted to each other.

[0411] Figure 4 A side view of the tips (6) is shown. These tips have a male Luer lock connector (6a) that enables the mixing cartridge (I) to be connected to a syringe and locked onto the syringe.

[0412] Figure 5 A cross-sectional view of the tips (6) is shown. These tips (6) are fitted into the perforated body (8) via circular notches (6b) so as to adapt to the reduced diameter (8b) of the perforated body (8), or are fitted into the perforated body (7) via circular notches (6b) so as to adapt to the reduced diameter (7b) of the perforated body (7).

[0413] Figure 6 A front view of the tip (6) is shown.

[0414] Figure 7A side view of a single-hole body (7) is shown, which can be connected to a tip (6) on one side by a reduction in the outer diameter (7a).

[0415] Figure 8 A cross-sectional view of a single-hole body (7) is shown, which can be connected to a perforated body (8) on one side by a circular notch (7b). This part has a plane perpendicular to the wall (7c), which is perforated with a hole parallel to the wall (7d). The hole is provided on the side connected to the tip (6).

[0416] Fig. 9 A front view of a single hole body (7) is shown, with the hole (7d) being located in the centre of a plane perpendicular to the wall (7c).

[0417] Fig.10 A side view of a perforated body (8) is shown which can be connected to the tip (6) on one side by a reduction in outer diameter (8a) and to the monopore body (7) on the other side by a reduction in outer diameter (8b).

[0418] Fig.11 A cross-sectional view of the perforated body (8) is shown, the portion having a plane perpendicular to the wall (8c) perforated with a plurality of holes parallel to the wall (8d). These holes are arranged on the side where the outer diameter (8a) is reduced, allowing connection with the tip (6).

[0419] Fig.12 A front view of the perforated body (8) is shown, with holes (8d) located on the periphery in a plane perpendicular to the wall (8c). This allows alternation of fluid movement within the mixing cartridge (I) without preferential pathways, thereby producing a static mixture of gel components according to the invention.

[0420] Fig.13 Shown is an overall view of an assembled mixing cartridge (II), which is composed of two separate bodies: body (10) and body (9). The different parts constituting the mixing cartridge (II) are assembled to each other.

[0421] Fig.14 A cross-sectional view of an assembled mixing cartridge (II) is shown, showing the two parts (9) and (10) forming the body of the cartridge fitted to each other, and showing that the device contains a mixing crossbar (11).

[0422] Fig.15 A side view of the body (10) is shown. The body (10) has a male Luer lock connector (10a) that enables the mixing cartridge (II) to be connected and locked on the syringe. The body (10) is assembled with the body (9) by a reduction in the outer diameter (10b).

[0423] Fig.16A cross-sectional view of the body (10) is shown.

[0424] Fig.17 A front view of the body (10) is shown.

[0425] Fig.18 A side view of the body (9) is shown. The body (9) has a male Luer lock connector (9a) that enables the mixing cartridge (II) to be connected and locked onto a syringe.

[0426] Fig.19 A cross-sectional view of the body (9) is shown. The body (9) fits onto the body (10) via a circular notch (9b) to accommodate the reduction in diameter (10b) of the body (10).

[0427] Fig. 20 A front view of the body (9) is shown.

[0428] Fig.21 Shown is a side view of a crossbar (11) which facilitates static mixing of the gel components according to the present invention. The mixing crossbar (11) is enclosed in a mixing cartridge (II) within the space formed by the assembly of the body (10) and the body (9).

[0429] Fig. 22 An overall view of the crossbar (11) is shown.

[0430] Fig.23 A front view of the crossbar (11) is shown.

[0431] Fig.24 Shown is an overall view of the assembled mixing cartridge (III), which is composed of the tip (12), the perforated body (13) and the connector (14). The different parts that make up the mixing cartridge (III) are assembled to each other.

[0432] Fig.25 A cross-sectional view of the assembled mixing cartridge (III) is shown, showing the various parts of which it is composed, (12) to (13) and (14) fitted to one another, and showing that the device includes a mixing crossbar (15) at the connector (14).

[0433] Fig.26 A side view of the tip (12) is shown. The tip has a male Luer lock connector (12a) that enables the mixing cartridge (III) to be connected and locked onto the syringe.

[0434] Fig. 27 A cross-sectional view of the tip (12) is shown. The tip (12) fits to the perforated body (13) via a circular notch (12b) to accommodate the reduction in diameter (13b) of the perforated body (13).

[0435] Fig.28 A front view of the tip (12) is shown.

[0436] Fig.29 A side view of a perforating body (13) is shown, which can be connected to the tip (12) on one side by a reduction in outer diameter (13a) and to the connector (14) on the other side by a reduction in outer diameter (13b).

[0437] Fig.30 A cross-sectional view of the perforated body (13) is shown, the portion having a plane perpendicular to the wall (13c) perforated with a plurality of holes parallel to the wall (13d). These holes are provided on the side (13a) connected to the tip (12).

[0438] Fig.31 A front view of a perforated body (13) is shown with holes (13d) located on the periphery in a plane perpendicular to the wall (13c) which allows alternation of fluid movement within the mixing cartridge (III) without preferential pathways, thereby producing a static mixture of gel components according to the invention.

[0439] Fig.32 Shown is a side view of a crossbar (15) which facilitates static mixing of the gel components according to the invention. The mixing crossbar (15) is enclosed in a mixing cartridge (III) within the space formed by the assembly of the perforated body (13) and the connector (14).

[0440] Fig.33 An overall view of the crossbar (15) is shown.

[0441] Fig.34 A front view of the crossbar (15) is shown.

[0442] Fig.35 A side view of the connector (14) is shown. The connector (14) has a male Luer lock connector (14a) that enables the mixing cartridge (III) to be connected and locked onto a syringe.

[0443] Fig.36 A cross-sectional view of the connector (14) is shown. The connector (14) fits to the perforated body (13) via a circular notch (14b) to accommodate the reduction in diameter (13b) of the perforated body (13).

[0444] Fig.37 A front view of the connector (14) is shown.

[0445] The following examples are provided to illustrate the invention. Example

[0446] Example 1: Hyaluronic acid gel

[0447] Commercial non-cross-linked hyaluronic acid gel (Product Hydro (VIVACY)) and a commercial cross-linked hyaluronic acid gel containing a local anesthetic (the product Juvederm (ALLERGAN)) are used to prepare the fat and hyaluronic acid emulsions according to the invention. These commercial hyaluronic acid gels are available in 1 ml syringes.

[0448] Example 2: Method for recovering fat for preparing fat emulsion.

[0449] Fat tissue, called liposuction fat, is preferably harvested from the abdomen or knee during surgery with the consent of a suitable donor.

[0450] The fat harvesting was performed under anesthesia using standard surgical techniques according to a protocol involving, inter alia: determining the area of ​​the body to be sampled; making an incision in the harvesting area with or without subsequent infiltration with Klein serum; using specific The brand's Tonnard cannula captures fat for liposuction and transfers the fat from the cannula into a sterile syringe under vacuum using a back and forth motion in the tissue and a fanning motion of the cannula to prevent bleeding and achieve a uniform appearance after collection.

[0451] 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.

[0452] The syringe filled with fat is ready to use or can be placed in a refrigerator prior to use.

[0453] Example 3: Method for preparing fat emulsion for fat filling

[0454] The recovered fat for liposuction was collected using a sterile 5 ml syringe equipped with a Luer lock system.

[0455] The sterile syringe is connected to one of the inlets of a sterile three-way valve or to one of the inlets of a sterile double Luer lock connector, whereas an empty sterile 5 ml syringe equipped with a Luer lock system is connected to one of the other inlets.

[0456] To obtain a homogenous emulsion based solely on lipofilling fat, the plunger is moved rapidly back and forth between two sterile syringes connected to each other by a three-way valve or a double Luer lock connector. At least 40 back and forth movements are required to obtain a satisfactory emulsion of lipofilling fat.

[0457] Example 4: Method for preparing an emulsion of fat and hyaluronic acid for fat filling according to the present invention

[0458] 4 ml of recovered fat for liposuction was collected using a sterile 5 ml syringe equipped with a Luer lock system.

[0459] The sterile syringe was connected to one of the inlets of a sterile three-way valve or to one of the inlets of a sterile double Luer lock connector, and a syringe containing 1 ml of hyaluronic acid gel was connected to one of the other inlets.

[0460] The hyaluronic acid gel is then introduced into a sterile syringe containing the fat for liposuction.

[0461] The syringe containing the hyaluronic acid gel was replaced with an empty sterile 5 ml syringe equipped with a Luer lock system.

[0462] To obtain a homogenous emulsion based on fat and hyaluronic acid for lipofilling, the plunger is moved back and forth rapidly between two sterile syringes connected to each other by a three-way valve or a double Luer lock connector. At least 40 back and forth movements are required to obtain a satisfactory emulsion of fat and hyaluronic acid for lipofilling.

[0463] In a variant, a kit comprising a cartridge as defined above is used to obtain a homogenous emulsion.

[0464] Example 5: Storage stability of the emulsion of fat and hyaluronic acid for fat filling according to the present invention.

[0465] According to the method of Example 2, the product The stability of the emulsions of fat for lipofilling and hyaluronic acid prepared by Hydro was monitored visually during horizontal storage on a table at 20°C, 2 hours and 4 hours after their preparation.

[0466] The stability of the fat emulsion for fat filling prepared according to the method of Example 1 was also evaluated in parallel according to the same protocol.

[0467] The results of this stability study are described in Table 1.

[0468] Table 1

[0469]

[0470] The pure emulsion of fat for fat filling degraded rapidly as shown by the formation of two phases after 2 hours of storage at room temperature.

[0471] The emulsion of fat and hyaluronic acid for fat augmentation according to the invention is stable at room temperature for at least 4 hours.

[0472] The stability of the emulsion of fat and hyaluronic acid for lipofilling according to the present invention provides the surgeon with flexibility and comfort in its use during surgical procedures.

[0473] Example 6: Injectability of the emulsion of fat and hyaluronic acid for fat filling according to the present invention

[0474] Starting from a freshly prepared emulsion and after storage at 20°C for 4 hours and 30 minutes, the emulsion prepared by the method of Example 2 was evaluated through a 27G and 25G cannula. The emulsion of fat and hyaluronic acid for fat filling prepared by Hydro and the product Juvederm according to the method of Example 2 Preparation of injectable emulsions of fat and hyaluronic acid for lipofilling.

[0475] For comparison, the injectability of freshly prepared fat emulsions for liposuction was evaluated through 27G and 25G cannulas.

[0476] The results of injectability are shown in Table 2.

[0477] Table 2

[0478]

[0479] The results obtained indicate that the emulsion of lipofilling fat and hyaluronic acid according to the invention allows the surgeon to use a cannula of smaller dimensions than cannulae that can be used to inject pure emulsion of lipofilling fat.

[0480] The emulsion of fat and hyaluronic acid for lipofilling according to the present invention can still be injected with a small-sized cannula at least 4.5 hours after its preparation, which provides comfort and flexibility in use during surgical procedures.

[0481] Example 7: Appearance of the emulsion of fat and hyaluronic acid for fat grafting according to the present invention after passing through the cannula

[0482] The stability of the fresh emulsions according to the invention and the stability 4.5 hours after their preparation were evaluated by visual observation of the sediment obtained after passing through a 25G cannula.

[0483] The emulsion tested was the same as that of Example 4.

[0484] The observed results for these different emulsions are shown in Table 3.

[0485] Table 3

[0486]

[0487] The emulsion of lipofilling fat and hyaluronic acid according to the invention has a better consistency after passing through the cannula than an emulsion of pure lipofilling fat, even after storage for 4.5 hours at room temperature.

[0488] The emulsion of fat for fat grafting and hyaluronic acid according to the present invention has a ductility close to that of a gel, and this characteristic is different from that of fat grafting fat alone. The emulsion obtained according to the present invention behaves like a modeling paste, which is a characteristic different from that of fat grafting fat alone.

[0489] Example 8: Rheological properties of the emulsion of fat and hyaluronic acid for fat filling according to the present invention

[0490] Viscoelastic properties were measured using a TA Instrument AR2000 rheometer. Measurements were performed at 25°C with a 2° 40 mm cone geometry at a deformation of 0.8% using a sweep frequency from 0.08 Hz to 5 Hz.

[0491] The fat emulsion for fat filling prepared according to Example 1 and the product prepared according to Example 2 were measured. Viscoelastic properties of emulsions of fat and hyaluronic acid for lipofilling prepared by Hydro.

[0492] Results of G' and Tanδ measurements at 1 Hz for different studied samples and the cutoff frequency f of the G' and G" curves 截止 This is shown in Table 4 below.

[0493] Table 4

[0494]

[0495] According to the present invention, The rheological properties of the emulsion of fat and hyaluronic acid for lipofilling prepared with the Hydro product were not affected by passage through a 25G cannula.

[0496] It can be noted that according to the present invention, the product The emulsion of fat and hyaluronic acid for fat filling prepared by Hydro has similar properties to commercial hyaluronic acid gel. The Tanδ value of Hydro is close to the Tanδ value of.

[0497] According to the present invention, The rheological properties of emulsions of lipofilling fat and hyaluronic acid prepared with the Hydro product are much more attractive than those of emulsions of pure lipofilling fat.

[0498] Example 9: Microscopic analysis of an emulsion of fat and hyaluronic acid for lipofilling according to the invention.

[0499] Microscopic analysis was performed using a Zweiss AXIO Scope A1 light microscope equipped with Filtrex software and at ×20 magnification.

[0500] Three types of samples were analyzed under a microscope: a sample of fat for fat filling, a sample of the fat emulsion for fat filling prepared according to Example 1, and a sample of the product prepared according to Example 2. Sample of an emulsion of fat and hyaluronic acid for lipofilling according to the invention prepared by Hydro.

[0501] The different observation results of the samples under the microscope are shown in Table 5 below.

[0502] Table 5

[0503]

[0504]

[0505] The emulsion of fat and hyaluronic acid according to the invention has a more homogeneous appearance, with small fat globules incorporated in a hyaluronic acid matrix.

[0506] Example 10: Comparative Clinical Study

[0507] Two groups of patients were formed, A and B. A contained 40 patients and B contained 40 patients, for a total of 80 patients.

[0508] Group A received injection lipofilling for facial rejuvenation using an emulsion of fat and hyaluronic acid, while Group B received injection lipofilling for facial rejuvenation using fat.

[0509] For each patient in Group A, an emulsion of hyaluronic acid and fat for fat grafting taken from the patient was prepared according to the method of Example 4. The hyaluronic acid used was product Hydro, its concentration in mannitol phosphate buffer (VIVACY Laboratories) was 14 mg / g, the fat was a washed and decanted MICROFAT type fat for fat filling, and the volume ratio of hyaluronic acid to fat was 1:4.

[0510] For each patient of Group B, fat for liposuction was obtained from the patient and was of the MICROFAT type.

[0511] At D0, fat was removed from the abdominal area of ​​each patient according to the protocol described in Example 2.

[0512] Injections into the face were performed using a TSK brand 25G Steriglide cannula after a pre-drilled hole was created using a TSK brand 23G Steriglide pre-drilled needle.

[0513] The practitioner responsible for the injection rated the volume injected per half of the face and assessed the ease of injection of the product using an injectability score. This 0 to 3 score was evaluated as follows:

[0514] 0: Not injectable: The product does not come out.

[0515] 1: Poor syringeability: Very high force is required to expel the product from the syringe, the product discharge flow is irregular and the cannula is clogged.

[0516] 2: Moderate syringeability: A large force is required to expel the product from the syringe, and the product discharge stream is accompanied by a jerk.

[0517] 3: Good injectability: moderate to low force is required to eject the product, injection is smooth and continuous,

[0518] No jerkiness.

[0519] The applicator also rated the spreadability of the product as it set using a 2-point scale:

[0520] 0: The product is not extensible: it does not deform and remains in lumps or disperses when kneaded or under finger pressure in an uncontrolled manner.

[0521] 1: The product is extensible: it stays in place by kneading or finger pressure.

[0522] On D+1, the injecting practitioner evaluated adverse effects in terms of incidence and severity, and patient rejuvenation was assessed using a patient satisfaction rating from 1 to 3:

[0523] 1: Unsatisfactory rejuvenation effect

[0524] 2: Moderately satisfactory rejuvenation effect

[0525] 3: Satisfactory rejuvenation effect

[0526] 4: Very satisfactory rejuvenation effect, intend to repeat

[0527] The results are summarized in Table 6 below:

[0528] Table 6

[0529]

[0530] These examples show that the gel according to the invention composed of lipofilling fat and hyaluronic acid makes it possible to obtain much more satisfactory rejuvenation results than the injection of lipofilling fat alone.

[0531] The gel according to the invention makes it possible to increase the extensibility of fat for lipofilling.

[0532] The gel according to the invention makes it easier to inject lipofilling fat, since there is no problem of cannula clogging, unlike in tests performed with lipofilling fat alone.

[0533] Furthermore, the injection of the gel according to the invention makes it possible to significantly limit the occurrence of side effects after injection. In fact, it was shown that only 5% of side effects (such as bruises) were observed with the gel according to the invention, compared to 50% with the injection of fat alone for lipofilling.

[0534] Example 11: In vitro injectability study of 10 samples

[0535] Mix 4cc of MICROFAT or NANOFAT type fat with 1cc of Hydro products are mixed, The Hydro product is a hyaluronic acid gel at a concentration of 14 mg / g in mannitol phosphate buffer, sold by VIVACY Laboratories, with a volume ratio of hyaluronic acid to fat of 1:4.

[0536] Manual syringeability testing was performed using a TSK Steriglide brand cannula and a BD brand 10 cc Luer lock syringe.

[0537] The choice of cannula is made among cannulae dedicated for injectable filling products (22G to 27G), ie, the size of the cannulae is smaller than the fat filling cannulae (19G to 21G) commonly used during surgical procedures.

[0538] The practitioner blindly assessed injectability and assigned an injectability score using the following injectability scale:

[0539] 0: Not injectable: The product does not come out.

[0540] 1: Poor syringeability: Very high force is required to expel the product from the syringe, the product discharge flow is irregular and the cannula is clogged.

[0541] 2: Moderate syringeability: A large force is required to expel the product from the syringe, and the product discharge stream is accompanied by a jerk.

[0542] 3: Good injectability: moderate to low force is required to eject the product, injection is smooth and continuous, without jerkiness

[0543] The results are summarized in Table 7 below:

[0544] Table 7

[0545]

[0546]

[0547] For the same cannula size, the injectability is at least the same or - even more generally - better than the object of the invention. This allows on the one hand to perform injections with smaller cannulas, which are therefore less traumatic for the patient, and on the other hand facilitates the practitioner's work because the action is smoother and more precise.

[0548] Example 12: Non-comparative clinical study of 45 cases

[0549] The gel studied in this example is produced by the conversion of fat into NANOFAT and the product Hydro composition, the product Hydro is a hyaluronic acid gel at a concentration of 14 mg / g in mannitol phosphate buffer, sold by VIVACY Laboratories, with a hyaluronic acid to fat ratio of 1:4 by volume.

[0550] Combine 4cc of NANOFAT with 1cc A non-comparative study of a mixture of Hydro products was conducted in 45 clinical cases over a 2-year period.

[0551] At D0, fat was removed from the abdominal area of ​​each patient and then injected into the face in the zygomatic area for facial rejuvenation using a 25G cannula. Each patient was injected on each side of the face and thus underwent 2 injection procedures.

[0552] Thus 90 injection operations were performed.

[0553] The results are summarized in Table 8 below:

[0554] Table 8

[0555]

[0556] The clinical study showed that this new method of skin rejuvenation satisfied all treated patients, with the vast majority stating that they were very satisfied. Furthermore, the effects were still evident more than a year after the procedure. Finally, side effects were rare, limited and mild.

Claims

1. An emulsion, gelled emulsion or gel comprising a hydrogel and a fat or a fat derivative.

2. The emulsion, gelled emulsion or gel according to claim 1, characterized in that The fat is MICROFAT or lipofilling fat, ie fat consisting of adipose tissue harvested using a small diameter cannula that has not undergone any transformation or alteration.

3. The emulsion, gelled emulsion or gel according to claim 1, characterized in that The fat is NANOFAT or fat consisting of explanted adipose tissue that has been subjected to the mechanical action of a knife to liquefy it and then filtered to obtain a highly fluid, cell-rich mass.

4. An emulsion, gelled emulsion or gel according to any one of the preceding claims, characterised in that The emulsion, gelled emulsion or gel further comprises an active ingredient selected from the group consisting of a local anesthetic, a vitamin C derivative, an anti-inflammatory agent, an antioxidant, and mixtures thereof.

5. An emulsion, gelled emulsion or gel according to any one of the preceding claims, characterised in that The hydrogel is composed of at least one polysaccharide selected from the group comprising hyaluronic acid, keratan, heparin, cellulose, cellulose derivatives (particularly hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylmethylcellulose, carboxymethylcellulose), alginic acid, xanthan gum, carrageenan, chitosan, chondroitin, heparin precursors, and biologically acceptable salts thereof, alone or as a mixture.

6. The emulsion, gelled emulsion or gel according to claim 6, characterized in that The polysaccharide comprises at least one hyaluronic acid or a salt thereof, alone or as a mixture.

7. The emulsion, gelled emulsion or gel according to claim 7, characterized in that The polysaccharide is hyaluronic acid in the form of a sodium or potassium salt.

8. An emulsion, gelled emulsion or gel according to any one of claims 6 to 8, characterized in that The polysaccharide is non-cross-linked hyaluronic acid or a salt thereof, alone or as a mixture.

9. An emulsion, gelled emulsion or gel according to any one of claims 6 to 8, characterized in that The polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture.

10. The emulsion, gelled emulsion or gel according to claim 10, characterized in that The polysaccharide is cross-linked hyaluronic acid or a salt thereof, alone or as a mixture, the cross-linking being carried out by at least one bifunctional cross-linking agent, the at least one bifunctional cross-linking agent being butanediol diglycidyl ether (BDDE) or 1,2,7,8-diepoxyoctane.

11. An emulsion, gelled emulsion or gel according to any one of claims 6 to 11, characterised in that The molecular weight mw of the at least one hyaluronic acid is in the range of 0.01 MDa to 5 MDa.

12. An emulsion, gelled emulsion or gel according to any one of claims 6 to 12, characterised in that The concentration of hyaluronic acid [HA] in the hydrogel is 2 mg / g to 50 mg / g of the total weight of the hydrogel.

13. An emulsion, gelled emulsion or gel according to any one of the preceding claims, characterised in that The hydrogel is sterile, which means that it has undergone a sterilization step after its preparation, which has been carried out by heating, by moist heat, by gamma radiation (γ), by accelerated electron beams, or by sterile filtration (0.22 μm) in the case of hydrogels based on non-crosslinked hyaluronic acid.

14. An emulsion, gelled emulsion or gel according to any one of the preceding claims, characterised in that The volume ratio of the hydrogel to the fat or fat derivative is 0.5 / 4.5 to 2 / 3.

15. Process for preparing an emulsion, gelled emulsion or gel according to any one of the preceding claims, characterized in that The method comprises the following steps: a) providing fat or fat derivatives, b) providing a hydrogel, c) aseptically mixing the hydrogel with fat or a fat derivative, d) emulsifying the mixture until an emulsion, gelled emulsion or homogeneous gel is obtained.

16. A kit for preparing an emulsion, gelled emulsion or gel according to any one of the preceding claims, characterized in that The kit comprises a cartridge (4) and at least 2 syringes.

17. The kit according to claim 15, characterized in that The cartridge (4) comprises at least one hydrogel.

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