Hybrid polymers and methods for obtaining same - Patents.com

Abstract

The present invention belongs to the technical field of hybrid polymers. More specifically, the present invention relates to a specific hybrid polymer. The hybrid polymer is obtained by a radical polymerization method between at least one unsaturated ethylenic monomer and at least one protein. The present invention also relates to the use of the composition in various compositions. The present invention also relates to the use of such compositions in various application fields.

Description

[Technical Field]

[0001] The present invention belongs to the technical field of hybrid polymers. More specifically, the subject of the present invention is a specific hybrid polymer. The hybrid polymer is obtained by a free radical polymerization method between at least one unsaturated ethylenic monomer and at least one protein. The present invention also relates to the use of the hybrid polymer in various compositions. The present invention also relates to the use of these compositions in various fields of application. [Background technology]

[0002] The development of hybrid polymers, ie polymer entities that combine at least two polymers with different properties, has been the subject of considerable research in recent years.

[0003] These hybrid polymers have the advantage that, given the large number of possible polymer combinations, they can exhibit unique functional properties and application possibilities, thereby leading to new synergistic effects.

[0004] Such hybrid polymers include those that combine biopolymers derived from natural and / or renewable resources with synthetic polymers derived from fossil resources. This type of hybrid polymer has attracted significant interest in many industries due to its similar application performance and potential for sustainable development as synthetic polymers. These characteristics make them attractive polymers for many applications and also offer opportunities for the innovation and development of more efficient and environmentally friendly products.

[0005] Many documents present hybrid polymers combining polysaccharides with synthetic polymers or polysaccharides with synthetic monomers. U.S. Patents 5,854,191, 5,223,171, 5,227,446, and 5,296,470 disclose the use of such hybrid copolymers in cleaning applications. Documents WO / 1810663, WO / 18108665, and WO / 18108667 each disclose such hybrids for use in cosmetic formulations.

[0006] However, the use of such polysaccharide hybrid polymers remains very limited to certain application areas, mainly in cosmetics, and such polysaccharide hybrids are not found in applications where the hybrid polymer must withstand difficult conditions such as high temperature or pressure, such as, for example, petroleum applications or textiles. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] U.S. Patent No. 5,854,191 [Patent Document 2] U.S. Patent No. 5,223,171 [Patent Document 3] U.S. Patent No. 5,227,446 [Patent Document 4] U.S. Patent No. 5,296,470 [Patent Document 5] WO / 1810663 [Patent Document 6] WO / 18108665 [Patent Document 7] WO / 18108667 [Patent Document 8] FR3125048 [Patent Document 9] FR3125045 [Patent Document 10] FR3125044 [Patent Document 11] FR3125043 [Patent Document 12] FR3125046 [Patent Document 13] WO2023 / 281233 [Patent Document 14] EP4175939 [Patent Document 15] WO2023 / 281088 [Patent Document 16] WO2023 / 281077 [Patent Document 17] WO2023 / 281076 [Patent Document 18] WO2023 / 281078 [Patent Document 19] WO2023 / 281084 [Patent Document 20] WO2023 / 281081 [Patent Document 21] WO21123599 [Patent Document 22] WO2020 / 094960A1 [Non-patent literature]

[0008] [Non-Patent Document 1] Chapter 11 of the book "Handbook of Applied Surface and Colloid Chemistry" by K. Holmberg [Non-patent document 2] Griffin WC, Classification of Surface-Active Agents by HLB, Journal of the Society of Cosmetic Chemists, 1949, 1, pp. 311-326. Summary of the Invention [Problem to be solved by the invention]

[0009] It has become an immense need to develop hybrid polymers that meet the expectations of different specifications in different application areas. [Means for solving the problem]

[0010] The applicant has developed hybrid polymers that combine monomer units and protein units, which are included in compositions that themselves find use in a variety of applications.

[0011] One subject of the present invention is hybrid polymers (HP).

[0012] According to a first aspect, the present invention relates to a hybrid polymer (HP) comprising monomer units of at least one monomer comprising at least one unsaturated ethylenic functional group and protein units, characterized in that the monomer units and the protein units are partially or entirely linked by at least one covalent bond and the mass ratio of the monomer units to the protein units is between 50 / 1 and 1 / 5.

[0013] According to a second aspect, the present invention provides a method for producing a medicament for the treatment of a cancer, comprising the following sequential steps: (A) preparing a mixture (M1) comprising at least one monomer containing at least one unsaturated ethylenic functional group, and 0.1% to 50% by weight of at least one protein, and optionally at least one solvent; (B) initiating polymerization in the mixture (M1) to obtain a hybrid polymer (HP); The present invention relates to a hybrid polymer (HP) obtained by free radical polymerization according to a method comprising:

[0014] According to a third aspect, the present invention provides a method for producing a medicament for the treatment of a cancer, comprising the following sequential steps: (A1) preparing an aqueous phase containing 1% by mass to 50% by mass of at least one protein, 4% by mass to 40% by mass of at least one monomer containing at least one unsaturated ethylenic functional group, and 20% by mass to 95% by mass of water; (A2) preparing a lipophilic phase containing 70% to 99% by mass of an inert hydrophobic liquid and 1% to 20% by mass of at least one surfactant; (A3) mixing the aqueous phase with the lipophilic phase to form an inverse emulsion; (B) polymerizing the inverse emulsion to obtain an inverse emulsion hybrid polymer (HP); The present invention relates to hybrid polymers (HP) obtained by free radical inverse emulsion polymerization by a process comprising:

[0015] According to a fourth aspect, the present invention provides a method for producing a medicament for the treatment of a cancer, comprising the following sequential steps: (A) preparing an aqueous solution containing 10% to 40% by weight of at least one monomer containing at least one unsaturated ethylenic functional group, and 1% to 30% by weight of at least one protein, water, and optionally at least one pH adjuster; (B) initiating radical polymerization in aqueous solution to obtain a hybrid polymer (HP) in the form of a gel; (C) crushing and drying the resulting gel to obtain a hybrid polymer (HP) in powder form; The present invention relates to a hybrid polymer (HP) obtained by free radical gel polymerization by a method comprising:

[0016] According to a fifth aspect, the present invention relates to the use of a hybrid polymer (HP) according to the invention, in particular as a viscosity modifier.

[0017] This aspect of the invention also relates to the use of the hybrid polymers (HP) according to the invention in various compositions, and to compositions comprising at least one hybrid polymer (HP) according to the invention.

[0018] The invention also relates to the use of such compositions in fields selected from hydrocarbon recovery, well drilling and cementing, hydrocarbon well stimulation, water treatment, fermentation must treatment, sludge treatment, papermaking, construction, wood treatment, hydraulic composition treatment, mining, cosmetic formulation, detergent formulation, textile manufacturing, battery component manufacturing, geothermal applications, diaper manufacturing, or agriculture. DETAILED DESCRIPTION OF THE INVENTION

[0019] Definitions and Overview Throughout this application, the following definitions apply unless otherwise stated.

[0020] "Hydrophilic monomer" refers to a monomer having an octanol / water partition coefficient, Kow, of 1 or less, where Kow is determined at 25°C in an octanol / water mixture having a volume ratio of 1 / 1 at a pH of 6-8.

[0021] "Hydrophobic monomer" refers to a monomer having an octanol / water partition coefficient, Kow, greater than 1, where the partition coefficient, Kow, is determined at 25°C in an octanol / water mixture having a volume ratio of 1 / 1 at a pH of 6-8.

[0022] The octanol / water partition coefficient Kow represents the ratio of the concentration (g / l) of the monomer between the octanol phase and the aqueous phase. It is given by:

[0023]

number

[0024] (In the formula, [monomer]octanol = equilibrium solubility concentration of the monomer in g / l in n-octanol [monomer]water = equilibrium concentration of monomer in g / l in water) It is defined as follows:

[0025] "X and / or Y" is understood according to the present invention to mean "X" or "Y" or "X and Y".

[0026] All possible combinations of the various disclosed embodiments, whether they are preferred embodiments or embodiments given as examples, are also part of the present invention. Furthermore, where ranges of values ​​are given, the limits are part of these ranges. The present disclosure also includes all combinations between the limits of these value ranges. For example, the value range "1 to 20, preferentially 5 to 15" means the disclosure of the ranges "1 to 5," "1 to 15," "5 to 20," and "15 to 20," as well as the values ​​1, 5, 15, and 20.

[0027] According to the present invention, the weight average molecular weight of the synthetic polymer according to the present invention is determined by measuring the intrinsic viscosity. The intrinsic viscosity may be measured by methods known to those skilled in the art, and in particular may be calculated from the reduced viscosity values ​​at various concentrations by a graphical method consisting in plotting the reduced viscosity values ​​(y-axis) as a function of concentration (x-axis) and extrapolating the curve to zero concentration. The intrinsic viscosity values ​​are read on the y-axis or using the least squares method. Then, the well-known Mark-Houwink equation: [η]=KM α (In the formula, [η] represents the intrinsic viscosity of the polymer as determined by a method for measuring viscosity in solution; K represents an empirical constant, M represents the molecular weight of the polymer, α represents the Mark-Houwink coefficient, α and K depend on the particular polymer-solvent system. Tables known to those skilled in the art give values ​​of α and K depending on the polymer solvent system.

[0028] The term "monomer unit" refers to the chemical unit associated with the corresponding monomer when polymerized in the polymer chain of a polymer.

[0029] The term "protein unit" refers to the chemical unit associated with the corresponding protein when grafted onto the polymer chain of a polymer.

[0030] Hybrid Polymer (HP) According to a first aspect, the present invention relates to a hybrid polymer (HP) comprising monomer units of at least one monomer comprising at least one unsaturated ethylenic functional group and protein units, characterized in that the monomer units and the protein units are partially or entirely linked by at least one covalent bond and the mass ratio of the monomer units to the protein units is between 50 / 1 and 1 / 5.

[0031] The mass ratio of monomer units to protein units is between 50 / 1 and 1 / 5, preferentially between 25 / 1 and 1 / 3, more preferentially between 10 / 1 and 1 / 2, more preferentially between 6 / 1 and 1 / 1.

[0032] The hybrid polymer (HP) advantageously has a weight average molecular weight of between 20,000 and 20,000,000 Daltons, preferentially between 100,000 and 15,000,000 Daltons.

[0033] The hybrid polymer (HP) preferably has a Brookfield viscosity of 1,000 to 100,000 cPs, more preferably 2,500 to 75,000 cPs, and even more preferably 5,000 to 50,000 cPs. The Brookfield viscosity is measured on a 1% by weight aqueous solution of the polymer using a Brookfield RVT unit viscometer at a rotation speed of 20 rpm.

[0034] The hybrid polymer (HP) comprises less than 40% by weight of protein, preferentially between 10% and 50% by weight of protein, and even more preferentially between 15% and 45% by weight of protein.

[0035] The hybrid polymer (HP) may be in the form of a solution, powder, inverse emulsion, water-in-water dispersion, suspension, or in "clear" form, i.e., a dispersion of solid polymer particles in an aqueous or oily fluid. If the hybrid polymer (HP) is in powder form, it may also be in the form of particles or beads.

[0036] According to the present invention, hybrid polymers (HP) can be linear or structured. Structured polymers refer to non-linear polymers with side chains that achieve a high degree of entanglement, which results in a very high viscosity at a low gradient when the polymer is dissolved in water. They are also called cross-linked polymers.

[0037] Monomers and monomer units: For the avoidance of doubt, the monomer units refer to the chemical units associated with the corresponding monomers when polymerized in the hybrid polymer (HP). The constituent monomers of the monomer units of the hybrid polymer (HP) are selected from monomers containing at least one unsaturated ethylenic functional group.

[0038] In the present application, the expressions "monomer unit" and monomer are used in an appropriate manner. For hybrid polymers (HP) according to the first aspect of the present invention, the expression "monomer unit" is appropriate and used, since the monomer reacts during polymerization and forms part of the polymer chain. For polymers (HP) obtained by a (free radical polymerization, or inverse emulsion polymerization, or gel polymerization) process, the expression "monomer" is appropriate and used, since the monomer is described in its pre-polymerization form.

[0039] If a claim refers, on the one hand, to at least one claim of the type "hybrid polymer (HP) comprising ..." and, on the other hand, to at least one claim of the type "hybrid polymer (HP) obtained by a (free radical polymerization, or inverse emulsion polymerization, or gel polymerization) process", both expressions can be used in the same sentence, e.g., in the claim. The monomers and preferences mentioned below are also applicable to both expressions.

[0040] This includes the monomers of the following patents, as the monomers may be synthetic and / or bio-based in nature: FR3125048, FR3125045, FR3125044, FR3125043, FR3125046, WO2023 / 281233, EP4175939, WO2023 / 281088, WO2023 / 281077, WO2023 / 281076, WO2023 / 281078, WO2023 / 281084, WO2023 / 281081.

[0041] Preferentially, these monomers are hydrophilic monomers chosen from nonionic, anionic, cationic and / or zwitterionic hydrophilic monomers, preferably having a single ethylenic unsaturation (double bond between two carbon atoms).

[0042] Nonionic hydrophilic monomers include water-soluble vinyl monomers such as acrylamide, methacrylamide, N-alkylacrylamide, N-alkylmethacrylamide, N,N-dialkylacrylamide (e.g., N,N-dimethylacrylamide or N,N-diethylacrylamide), N,N-dialkylmethacrylamide, alkoxylated esters of acrylic acid, alkoxylated esters of methacrylic acid, N-vinylpyrrolidone, N-methylol (meth)acrylamide, N-vinylcaprolactam, N-vinylformamide (NVF), N-vinylacetamide, N-vinylimidazole, N- Preferentially, the nonionic monomers are selected from the group consisting of vinyl succinimide, acryloylmorpholine (ACMO), glycidyl methacrylate, glyceryl methacrylate, diacetone acrylamide, methacrylic anhydride, acrylonitrile, maleic anhydride, itaconic anhydride, itaconamide, vinylpyridine, hydroxyalkyl (meth)acrylates, thioalkyl (meth)acrylates, isoprenol and its alkoxylated derivatives, hydroxyethyl (meth)acrylate and its alkoxylated derivatives, hydroxypropyl acrylate and its alkoxylated derivatives, vinyl acetate, and mixtures thereof. In these nonionic monomers, the alkyl groups are preferably C1-C5, more preferably C1-C3 alkyl groups. They are preferably linear alkyl groups.

[0043] The nonionic monomer units account for 1 to 99 mol %, preferentially 2 to 70 mol %, of the monomer units of the hybrid polymer (HP).

[0044] The anionic hydrophilic monomers are preferentially chosen from acrylic acid, methacrylic acid, dimethylacrylic acid, itaconic acid, crotonic acid, maleic acid, fumaric acid, acrylamidoundecanoic acid, 3-acrylamido-3-methylbutanoic acid, maleic anhydride, strong acid type monomers having, for example, sulfonic or phosphonic acid type functional groups, such as vinylsulfonic acid, vinylphosphonic acid, allylsulfonic acid, methallylsulfonic acid, 2-methylidenepropane-1,3-disulfonic acid, 2-sulfoethyl methacrylate, sulfopropyl methacrylate, sulfopropyl acrylate, allylphosphonic acid, styrenesulfonic acid, 2-acrylamido-2-methylpropanesulfonic acid (ATBS), 2-acrylamido-2-methylpropanedisulfonic acid, water-soluble salts of these monomers, such as alkali metal salts (different from the crystalline form of the sodium salt of 2-acrylamido-2-methylpropanesulfonic acid), alkaline earth metal salts or ammonium salts, and mixtures thereof.

[0045] The anionic monomer units represent 1 to 99 mol %, preferentially 2 to 70 mol %, more preferentially 3 to 50 mol % of the monomer units of the hybrid polymer (HP).

[0046] The term "salt" means that a proton from at least one acid functional group of the anionic monomer -R(=O)-OH (where R=P, S or C) is replaced by a metal or ammonium cation to form a salt of the type -R(=O)-OX (where X is a metal or ammonium cation). In other words, the non-salt form corresponds to the acid form of the monomer, e.g., RC(=O)-OH in the case of a carboxylic acid functional group, while the salt form of the monomer corresponds to RC(=O)O - X + (In the formula, X + corresponds to the form of a metal cation, preferentially an alkali metal cation or an ammonium cation). The salification of the acid functions of the polymer can be partial or complete.

[0047] The salt forms advantageously correspond to alkali metal (Li, Na, K, etc.) salts, alkaline earth metal (Ca, Mg, etc.) salts or ammonium salts (for example ammonium ions or tertiary ammonium salts). Preferred salts are sodium salts.

[0048] The salification may be carried out before or after the polymerization.

[0049] The cationic hydrophilic monomers are preferentially chosen from monomers derived from units of the vinyl type (advantageously acrylamide, acrylic, allyl or maleic type), these monomers bearing a phosphonium function, an ammonium salt or a quaternary ammonium salt.

[0050] In particular, mention may be made, but is not limited to, diallyldialkylammonium salts such as diallyldimethylammonium chloride (DADMAC), acidified or quaternized salts of dialkylaminoalkylacrylamides, for example, acidified or quaternized salts of dialkylaminoalkylmethacrylamides such as methacrylamidopropyltrimethylammonium chloride (MAPTAC) and acrylamidopropyltrimethylammonium chloride (APTAC), acidified or quaternized salts of dialkylaminoalkylacrylates such as quaternized or chlorinated dimethylaminoethylacrylate (ADAME), acidified or quaternized salts of dialkylaminoalkylmethacrylates such as quaternized or chlorinated dimethylaminoethylmethacrylate (MADAME), and mixtures thereof. Advantageously, the alkyl group is a C1-C3 alkyl group.

[0051] The cationic monomer units represent 1 to 99 mol %, preferentially 2 to 70 mol %, more preferentially 3 to 60 mol % of the monomer units of the hybrid polymer (HP).

[0052] Additionally, the present invention also encompasses DADMAC, APTAC and MAPTAC type monomers in which the counterion is sulfate, fluoride, bromide or iodide instead of chloride.

[0053] Preferentially, the cationic hydrophilic monomer is dimethylaminoethyl methacrylate in quaternized form.

[0054] Those skilled in the art will recognize how to prepare quaternized monomers, for example, by quaternizing agents of the RX type (R is an alkyl group and X is a halogen or sulfate).

[0055] "Quaternizing agent" refers to a molecule capable of alkylating a tertiary amine.

[0056] The quaternizing agent may be selected from dialkyl sulfates containing 1 to 6 carbon atoms or alkyl halides containing 1 to 6 carbon atoms. Preferentially, the quaternizing agent is selected from methyl chloride, benzyl chloride, dimethyl sulfate or diethyl sulfate.

[0057] The zwitterionic monomer is preferentially chosen from derivatives having units of vinyl type, in particular acrylamide, acrylic, allyl or maleic type. Preferentially, this monomer contains an amine or quaternary ammonium function and an acid function of carboxylic acid (or carboxylate), sulfonic acid (or sulfonate) or phosphoric acid (or phosphate) type. In particular, but without limitation, derivatives of dimethylaminoethyl acrylate, such as 2-((2-9-(acryloyloxy)ethyl)dimethylammonio)ethane-1-sulfonate, 3-((2-(acryloyloxy)ethyl)dimethylammonio)propane-1-sulfonate, 4-((2-(acryloyloxy)ethyl)dimethylammonio)butane-1-sulfonate, [2-(acryloyloxy)ethyl](dimethylammonio)acetate, derivatives of dimethylaminoethyl methacrylate, such as 2-((2-(methacryloyloxy)ethyl)dimethylammonio)ethane-1-sulfonate, 3-((2-(methacryloyloxy)ethyl)dimethylammonio)propane-1-sulfonate, 4-(2-(methacryloyloxy)ethyl)dimethylammonio)butane-1-sulfonate, [2-(methacryloyloxy)ethyl](dimethylammonio)acetate dimethylammonio)acetate, derivatives of dimethylaminopropyl acrylamide such as 2-((3-acrylamidopropyl)dimethylammonio)ethane-1-sulfonate, 3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate, 4-((3-acrylamidopropyl)dimethylammonio)butane-1-sulfonate, [3-(acryloyl)oxy)propyl](dimethylammonio)acetate, dimethylaminopropylmethylacrylamide, 2-((3-methacrylamidopropyl)dimethylammonio)ethane-1-sulfonate, 3-(dimethylammonio)propane-1-sulfonate-4-((3-methacrylamidopropyl)dimethylammonio)butane-1-sulfonate, and [3-(methacryloyloxy)propyl](dimethylammonio)acetate, and mixtures thereof. Other zwitterionic monomers are described by the applicant in document WO21123599.

[0058] Preferentially, preferred hydrophilic monomers are acrylamide, acrylic acid, oligomers of acrylic acid, 2-acrylamido-2-methylpropanesulfonic acid (ATBS) and / or its salts, N-vinylformamide (NVF), N-vinylpyrrolidone (NVP), dimethyldiallylammonium chloride (DADMAC), quaternized dimethylaminoethyl acrylate (ADAME), quaternized dimethylaminoethyl methacrylate (MADAME).

[0059] According to one aspect of the present invention, the monomer having an ethylenic functional group may be selected from the hydrophilic monomers described above, and may also be selected from hydrophobic monomers.

[0060] For the preparation of the hybrid polymers (HP), it is also possible to use hydrophobic monomers having a Kow partition coefficient greater than 1. They are advantageously chosen in particular from: Esters of (meth)acrylic acid with alkyl, arylalkyl, and / or ethoxylated and / or propoxylated chains, derivatives of (meth)acrylamide with alkyl, arylalkyl, or dialkyl, and / or ethoxylated and / or propoxylated chains, cationic allyl derivatives with alkyl, arylalkyl, or dialkyl, and / or ethoxylated and / or propoxylated chains, hydrophobic anionic or cationic (meth)acryloyl derivatives, and anionic or cationic monomeric derivatives of (meth)acrylamide with hydrophobic chains. The alkyl groups of these hydrophobic monomers are preferably C6-C24 alkyl groups. The most preferred monomers are bromoalkylated derivatives of methacrylamide dimethylaminopropyl with C8-C16 alkyl chains and ethoxylated behenyl methacrylate. n-hexyl (meth)acrylate, n-octyl (meth)acrylate, octyl (meth)acrylamide, lauryl (meth)acrylate, lauryl (meth)acrylamide, myristyl (meth)acrylate, myristyl (meth)acrylamide, pentadecyl (meth)acrylate, pentadecyl (meth)acrylamide, cetyl (meth)acrylate, cetyl (meth)acrylamide, oleyl (meth)acrylate, oleyl (meth)acrylamide, erucyl (meth)acrylate, erucyl (meth)acrylamide, and combinations thereof. - LCST (Lower Critical Solution Temperature) and / or UCST (Upper Critical Solution Temperature) monomers or macromonomers. In other words, the hydrophobicity may originate from the LCST and / or properties of the monomers or macromonomers. Patent application WO2020 / 094960A1 mentions such macromonomers with LCST properties.

[0061] Among these hydrophobic monomers, - the alkyl groups are preferably C3 to C20, more preferentially C3 to C8 alkyl groups; C6 to C20 alkyls are preferably linear alkyls, while C3 to C5 alkyls are preferably branched; - the arylalkyl group is preferably a C7 to C25, more preferably a C7 to C15 arylalkyl group; the ethoxylated chain preferably contains between 6 and 100, and more preferentially between 10 and 40, -CH2-CH2-O- groups, The propoxylated chain preferably contains 1 to 50, more preferably 1 to 20 -CH2-CH2-CH2-O- groups.

[0062] According to this aspect of the invention, preferred hydrophobic monomers are selected from N-isopropylacrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, N-tert-butylacrylamide, N-vinylcaprolactam, and diacetoneacrylamide.

[0063] Further according to this aspect of the invention, the concentration of the hydrophobic monomer is preferably between 0.0001 and 10 mol%, more preferentially between 0.001 and 5 mol%, even more preferentially between 0.01 and 3 mol%, even more preferentially between 0.1 and 2 mol%, even more preferentially between 0.2 and 1.5 mol%, even more preferentially between 0.3 and 1.3 mol%, the molar percentages being expressed relative to the total number of moles of monomers in mixture (M1).

[0064] The amount of the various monomers is adjusted by the person skilled in the art during the preparation of the water-soluble polymer according to the invention so as not to exceed 100 mol %.

[0065] Proteins and protein units For the avoidance of doubt, protein units refer to units associated with the corresponding protein when grafted onto the hybrid polymer (HP).

[0066] In the present application, the expressions "protein unit" and "protein" are used in an appropriate manner. For hybrid polymers (HP) according to the first aspect of the present invention, the expression "protein unit" is appropriate and used, since at least one protein reacts during polymerization and forms part of the polymer chain. For polymers (HP) obtained by a (free radical polymerization, or inverse emulsion polymerization, or gel polymerization) process, the expression "protein" is appropriate and used, since the protein is described in its pre-polymerization form.

[0067] If a claim refers, on the one hand, to at least one claim of the type "hybrid polymer (HP) comprising ..." and, on the other hand, to at least one claim of the type "hybrid polymer (HP) obtained by a (free radical polymerization, or inverse emulsion polymerization, or gel polymerization) process", both expressions can be used in the same sentence, e.g., in the claim. The following terms and preferences are also applicable to both expressions.

[0068] Herein, the term "protein" is used to include both native (or chemically unmodified) proteins and modified proteins. The term "modified protein" refers to a protein that has undergone one or more pretreatments. These pretreatments can be physical in nature, by shearing, or chemical in nature, by acid or alkaline hydrolysis and / or enzymatic hydrolysis via proteases.

[0069] The protein is obtained by conventional methods known to those skilled in the art, such as dissolving, grinding, screening and classification. The protein may be added to the mixture (M1) in solid or liquid form. Advantageously, the protein is added in powder form.

[0070] Advantageously, the native protein is preferred.

[0071] The proteins that make up the protein units of the hybrid polymer (HP) may be of animal origin; examples of animal proteins that may be mentioned include milk proteins such as β-lactoglobulin, casein and whey, serum proteins such as horse serum, placental proteins, fibrous dermal proteins such as collagen and elastin, and silk proteins.

[0072] The protein according to the invention may be of plant origin, such as corn, wheat, barley, oats, soybeans or peas, and may be, for example, glutelin, prolamin, zein and gluten. Preferentially, the plant protein is selected from soybean protein, wheat protein, oat protein and pea protein. Proteins may also be obtained from seeds, such as soybeans, cottonseed, peanuts, sunflowers, rapeseed, coconuts, flaxseeds, sesame, safflowers, peas, beans and lentils.

[0073] There are also proteins of bacterial and fungal origin, as well as proteins derived from algae and yeast.

[0074] Proteins may be soluble or insoluble in water, and the choice of protein solubility is of great interest in terms of the desired end use.

[0075] To convert proteins into a soluble form, they often require physical, chemical, or enzymatic treatment, such as acid or alkaline hydrolysis, yeast, bacterial, or enzymatic fermentation, extraction methods to remove trace components, coagulation from the extract by heating, digestion by addition of electrolytes, pH adjustment, or addition of precipitating agents.

[0076] Preferentially, the selected protein is soluble in water.

[0077] Preferentially, the protein selected is casein, a serum protein or a wheat protein.

[0078] Alternatively, the proteins may be present in the form of a mixture, which means a mixture comprising several proteins originating from the same or different kingdoms of life, such as a mixture comprising several proteins of animal origin, or a mixture comprising at least one protein of animal origin and at least one protein of plant origin and / or one protein of bacterial origin.

[0079] The proteins used in the graft copolymerization may be chemically modified in various ways before or after the graft polymerization.

[0080] Hybrid polymers (HP) obtained by free radical polymerization According to a second aspect, the present invention provides a method for producing a medicament for the treatment of a cancer, comprising the following sequential steps: (A) preparing a mixture (M1) comprising at least one monomer containing at least one unsaturated ethylenic functional group, and 0.1% to 50% by weight of at least one protein, and optionally at least one solvent; (B) initiating polymerization in the mixture (M1) to obtain a hybrid polymer (HP); The present invention relates to a hybrid polymer (HP) obtained by free radical polymerization according to a method comprising:

[0081] The mixture (M1) comprises preferentially 5% to 90% by weight, more preferentially 10% to 80% by weight, more preferentially 15% to 80% by weight, more preferentially 20% to 80% by weight, more preferentially 25% to 80% by weight, more preferentially 30% to 80% by weight, more preferentially 35% to 75% by weight, more preferentially 40% to 75% by weight, more preferentially 45% to 75% by weight, more preferentially 50% to 70% by weight, more preferentially 55% to 65% by weight of at least one monomer containing at least one unsaturated ethylenic functional group.

[0082] The mixture (M1) comprises preferentially 0.1% to 50% by weight, more preferentially 1% to 40% by weight, more preferentially 3% to 35% by weight, more preferentially 5% to 30% by weight, more preferentially 10% to 25% by weight of at least one protein.

[0083] The mixture (M1) comprises preferentially 1% to 90% by weight, more preferentially 5% to 80% by weight, more preferentially 10% to 70% by weight, more preferentially 15% to 60% by weight, more preferentially 20% to 50% by weight of at least one solvent.

[0084] The present invention particularly relates to a method for producing a process comprising the following sequential steps: (A) preparing a mixture (M1) containing 5% by mass to 90% by mass of at least one monomer containing at least one unsaturated ethylenic functional group, 0.1% by mass to 50% by mass of at least one protein, and at least 1% by mass of a solvent; (B) initiating polymerization in the mixture (M1) to obtain at least one hybrid polymer (HP); The present invention relates to a hybrid polymer (HP) obtained by a free radical polymerization method comprising:

[0085] Suitable solvents may be polar or non-polar.

[0086] Non-polar solvents include cyclohexane, heptane, benzene, toluene, xylene, ethylbenzene, and linear, branched, or cyclic alkanes having 2 to 20 carbon atoms, dichloromethane, and ethyl acetate.

[0087] Preferentially, the hybrid polymer is polymerized by free radical polymerization in a polar solvent, which in this case comprises water, alcohols and / or ketones. It is possible to use a polar solvent or a mixture of polar solvents.

[0088] The alcohol or ketone is preferably selected from methanol, ethanol, 1-propanol, 2-propanol, 2-methyl-2-propanol, 1-butanol, 2-butanol, dimethyl ketone, diethyl ketone, pentan-2-one, butanone, tetrahydropyran, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxane, 1,4-dioxane. The mixture of polar solvents is preferably a mixture of protic solvents (proton donors).

[0089] The solvent is preferentially water.

[0090] The protein is added to the polymerization ingredients in mixture (M1) of step (A) of the method described in this second aspect of the present application.

[0091] Preferentially, a single protein is added to the polymerization feedstock to form a hybrid polymer (HP).

[0092] The polymerization is a free radical polymerization, which includes polymerization using photochemical (UV or radiation) initiators, azo initiators, thermal initiators, or redox salts, as well as controlled radical polymerization (CRP) or matrix polymerization techniques.

[0093] Controlled radical polymerization techniques include, but are not limited to, techniques such as iodine transfer polymerization (ITP), nitroxide-mediated polymerization (NMP), or atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization, including macromolecular design by xanthate exchange (MADIX) techniques, various variations of polymerization using organometallic compounds (organometallic-mediated radical polymerization (OMRP)), and organic heteroatom-mediated radical polymerization (OHRP).

[0094] The polymerization initiator preferably used may be selected from compounds that dissociate into radicals under polymerization conditions, such as organic peroxides, hydroperoxides, hydrogen peroxide, persulfates, azo compounds and redox catalysts.The use of water-soluble initiators is preferred.In some cases, it is advantageous to use a mixture of various polymerization initiators, such as a mixture of redox salts and azo compounds.

[0095] Advantageously, the amount of initiator is between 5 and 1000 ppm, preferentially between 10 and 500 ppm, and more preferentially between 20 and 100 ppm relative to the total mass of the polymerization raw materials.

[0096] The initiator may be added to the mixture (M1) all at once by pouring or batchwise to the medium.

[0097] Preferentially, the polymerization is carried out in a temperature range ranging from 20° C. to 160° C., preferably from 30° C. to 100° C. It is preferably carried out at atmospheric pressure.

[0098] According to the present invention, hybrid polymers (HP) can be linear or structured. Structured polymers refer to non-linear polymers with side chains that achieve a high degree of entanglement, which results in a very high viscosity at a low gradient when the polymer is dissolved in water. They are also called cross-linked polymers.

[0099] The polymers according to the invention may be structured by: at least one structuring agent which may be chosen from the group comprising polyethylenically unsaturated monomers (having at least two unsaturated functional groups), such as vinyl, in particular allyl, acrylic and epoxy functional groups, such as methylenebisacrylamide (MBA), triallylamine, or tetraallylammonium chloride or 1,2-dihydroxyethylenebis(N-acrylamide); and / or macroinitiators, such as polyperoxides, polyazo compounds, and polytransfer agents, such as polymercaptan (co)polymers, and polyols, and / or - Functionalized polysaccharides.

[0100] The amount of branching / crosslinking agent in the monomer mixture is advantageously less than 4% by weight, more advantageously less than 1% and even more advantageously less than 0.5% by weight relative to the monomer content (by weight). According to a particular embodiment, it may be at least equal to 0.00001% by weight relative to the monomer content.

[0101] The polymerization is preferably carried out in an inert gas atmosphere in the absence of atmospheric oxygen, for example using nitrogen, argon or carbon dioxide as the inert gas, or using enzymatic deoxygenation.

[0102] Advantageously, the monomer containing at least one unsaturated ethylenic functional group to be polymerized and the protein are introduced into the reaction vessel at the beginning together with at least one polymerization primer and polymerized by heating to the optimum polymerization temperature. It may be advantageous to use two or more proteins. The terms "polymerization initiator" and "polymerization primer" refer to the same product having the same function of initiating the polymerization reaction.

[0103] The order in which the reactants are metered into the polymerization reactor can be freely changed. When multiple monomers are used in the graft copolymerization, the individual monomers can be metered into the polymerization zone sequentially, in the form of a mixture, or simultaneously from separate metering means. For example, it is possible to heat the protein solution or dispersion in the reactor to the required polymerization temperature, and add the monomers and initiator continuously or in batches.

[0104] Similarly, the pH of the reaction medium can also affect the hybrid polymer (HP). Acidic or basic monomers can be used in the form of their corresponding salts. For example, acrylic acid is used in the form of the free acid or in the form of an alkali metal salt. The polymerization can be carried out in a pH range ranging from 1 to 14, preferably from 6 to 12. By changing the pH, it is possible, for example, to precipitate the graft copolymer from the solution. This possibility can be utilized during the processing, purification, and isolation of the graft copolymer.

[0105] According to the present invention, the hybrid polymer (HP) may have a linear, branched, star-shaped or comb-branched structure, which can be obtained, for example, by choosing the initiator, the transfer agent, the polymerization technique, such as reversible addition-fragmentation chain transfer polymerization (RAFT), nitroxide-mediated polymerization (NMP) or atom transfer radical polymerization (ATRP), the incorporation or concentration of structural monomers, according to the general knowledge of the person skilled in the art.

[0106] The hybrid polymer (HP) obtained by free radical polymerization may be in the form described above in the section "Hybrid Polymer (HP)." The factors relating to the weight average molecular weight and Brookfield viscosity of the polymer described above are applicable to the hybrid polymer (HP) obtained according to this aspect of the invention.

[0107] Hybrid polymers (HP) obtained by free radical inverse emulsion polymerization According to a third aspect, the present invention relates to a hybrid polymer (HP) obtained by free radical polymerization, said free radical polymerization being an inverse emulsion polymerization, in which case the polymer (HP) is in the form of an inverse emulsion or a powder obtained by drying the inverse emulsion.

[0108] In this application, the expression "inverse emulsion" refers to both inverse emulsions and inverse microemulsions. Inverse emulsion polymerization, or water-in-oil emulsion polymerization, consists of emulsifying an aqueous phase containing monomers and proteins in an organic phase. This emulsification is carried out by a water-in-oil inverting agent.

[0109] In the present invention, the term "inverting agent" refers to an agent capable of emulsifying oil in water. More specifically, an inverting agent is considered to be a surfactant with an HLB of 10 or more, and a surfactant is considered to be a surfactant with an HLB strictly less than 10. Surfactants with an HLB of 8 to 10 are considered wetting agents. Those skilled in the art may refer to Chapter 11 of the book "Handbook of Applied Surface and Colloid Chemistry" by K. Holmberg, if necessary.

[0110] The hydrophilic-lipophilic balance (HLB) of a chemical compound is a measure of its hydrophilic and / or lipophilic properties, determined by calculating values ​​for different regions of the molecule, as described by Griffin in 1949 (Griffin WC, Classification of Surface-Active Agents by HLB, Journal of the Society of Cosmetic Chemists, 1949, 1, pp. 311-326).

[0111] In this study, we adopted the Griffin method, which is based on the calculation of values ​​based on the chemical groups of a molecule. Griffin assigned a dimensionless number between 0 and 20 to provide information on solubility in water and oil. A substance with an HLB value of 10 is distributed between the two phases so that the hydrophilic groups (molecular weight Mh) protrude completely into the water, while the hydrophobic groups (molecular weight Mp) are adsorbed in the non-aqueous phase.

[0112] The HLB value of a substance having a total molecular weight M, a hydrophilic portion having a molecular weight Mh, and a hydrophobic portion having a molecular weight Mp is: HLB=20(Mh / Mp) is given by

[0113] According to this third aspect, the present invention provides a method for producing a medicament for the treatment of a cancer, comprising the following sequential steps: (A1) preparing an aqueous phase containing 1% by mass to 50% by mass of at least one protein, 4% by mass to 40% by mass of at least one monomer containing at least one unsaturated ethylenic functional group, and 20% by mass to 95% by mass of water; (A2) preparing a lipophilic phase containing 70% to 99% by mass of an inert hydrophobic liquid and 1% to 20% by mass of at least one surfactant; (A3) mixing the aqueous phase with the lipophilic phase to form an inverse emulsion; (B) polymerizing the inverse emulsion to obtain an inverse emulsion hybrid polymer (HP); The present invention relates to hybrid polymers (HP) obtained by free radical inverse emulsion polymerization by a process comprising:

[0114] Steps (A1), (A2) and (A3) correspond to the substeps of step (A) in the free radical polymerization process for obtaining a hybrid polymer (HP) according to the second aspect of the present invention. The inverse emulsion obtained in step (A3) corresponds to the mixture (M1) from step (A) in the free radical polymerization process for obtaining a hybrid polymer (HP) according to the second aspect of the present invention.

[0115] The weight ratio of the aqueous phase to the lipophilic phase is preferably between 20 / 80 and 80 / 20, more preferentially between 70 / 30 and 30 / 70.

[0116] The inversion agent is preferentially added to the inverse emulsion after the polymerization step.

[0117] In step (A1), an aqueous phase is prepared by mixing at least one protein, at least one hydrophilic ethylenically unsaturated monomer, and water. The mixture may contain other compounds, such as a crosslinker.

[0118] The aqueous phase of step (A1) comprises between 1% and 50% by weight, preferentially between 1% and 40% by weight, more preferably between 1% and 40% by weight, of at least one protein, the protein being selected from those mentioned above with the same preferences.

[0119] The aqueous phase in step (A1) contains 4% to 40% by mass, preferably 10 to 35% by mass, more preferably 20 to 35% by mass of at least one hydrophilic ethylenically unsaturated monomer. The monomer containing at least one ethylenically unsaturated functional group is selected from the above-mentioned monomers containing at least one ethylenically unsaturated functional group having the same preference.

[0120] The aqueous phase of step (A1) comprises from 20% to 95% by weight, preferentially from 25% to 80% by weight, more preferentially from 35% to 75% by weight of water.

[0121] The aqueous phase is preferentially prepared at a solids concentration of 20% to 45% by weight. The skilled person will know how to adjust the ratio of monomer to protein depending on the desired properties.

[0122] In step (A2), a lipophilic phase is prepared by mixing at least one inert hydrophobic liquid and at least one surfactant.

[0123] The lipophilic phase of step (A2) comprises from 70% to 99% by weight, preferentially from 75% to 96% by weight, more preferentially from 80% to 93% by weight of an inert hydrophobic liquid.

[0124] The lipophilic phase also contains an inert hydrophobic liquid or a mixture of inert hydrophobic liquids. The inert hydrophobic liquid preferably represents an oil or a water-immiscible solvent. The oil used to prepare the water-in-oil emulsion of the present invention may be a mineral oil, a vegetable oil, a synthetic oil, or a mixture of several of these oils. Examples of mineral oils are mineral oils containing saturated hydrocarbons of the aliphatic, naphthenic, paraffinic, isoparaffinic, cycloparaffinic, or naphthyl type. Examples of synthetic oils are hydrogenated polydecene or hydrogenated polyisobutene, esters such as octyl stearate or butyl oleate. ExxonMobil Exxsol® products are suitable oils.

[0125] More specifically, the lipophilic phase consists of a heavy oil, a light oil and a surfactant, and those skilled in the art will know how to adjust the ratio of these three compounds to obtain a stable system that can withstand distillation under reduced pressure.

[0126] The lipophilic phase of step (A2) comprises from 1% to 20% by weight, preferentially from 1% to 15% by weight, more preferentially from 3% to 12% by weight of at least one surfactant.

[0127] The lipophilic phase contains at least one "surfactant", otherwise called an emulsifier, which corresponds to an agent capable of emulsifying water in oil, more specifically an aqueous phase in a lipophilic phase.

[0128] Examples of such surfactants include polyesters having a molecular weight of 1000 to 3000, condensation products of poly(isobutenyl)succinic acid or anhydride with polyethylene glycol, block copolymers having a molecular weight of 2500 to 3500, such as those sold under the name Hypermer®, sorbitan extracts such as sorbitan monooleate, sorbitan isostearate, or sorbitan sesquioleate, polyethoxylated sorbitan esters, or diethoxylated oleocetyl alcohol or tetraethoxylated lauryl acrylate, surfactant polymers, such as condensation products of higher fatty alcohols with ethylene oxide, such as the reaction product of oleyl alcohol with two ethylene oxide units, and condensation products of alkylphenols with ethylene oxide, such as the reaction product of nonylphenol with four ethylene oxide units. Products such as Witcamide® 511, betaine products, and ethoxylated amines are also excellent candidates as emulsifiers.

[0129] In a preferred embodiment, the surfactant is sorbitan monooleate, a polyethoxylated sorbitan ester, or tall oil fatty acid diethanolamine.

[0130] The surfactant may also be of bio-based nature selected from sucrose esters, alkyl polyglucosides (APGs), diglycerol esters, or phospholipids.

[0131] The inverse emulsion may comprise at least two surfactants in the lipophilic phase, preferably at least three surfactants, and better still at least four surfactants.

[0132] The inverse emulsion obtained according to the method preferably contains from 0.8% to 20% by weight, more advantageously from 1% to 10% by weight, of emulsifier.

[0133] In step (A3), the aqueous phase obtained in step (A1) and the lipophilic phase obtained in step (A2) are mixed to obtain an inverse emulsion. Generally, the step of emulsifying the two phases is carried out using means known to those skilled in the art.

[0134] As an example, in a reactor equipped with a temperature probe, an inert gas inlet, preferentially for nitrogen, and a mechanical stirrer, the lipophilic phase and then the aqueous phase are added before emulsification, thereby preferentially obtaining a stable inverse emulsion.

[0135] The medium obtained is then degassed with nitrogen before proceeding to the initiation of the polymerization, the subject of step (B), thereby obtaining the inverse emulsion hybrid polymer (HP), which is a free radical polymerization.

[0136] In certain embodiments, once the maximum temperature is reached, the system is subjected to aging.

[0137] After polymerization, an inverting agent is added to the inverse emulsion.

[0138] Inverting agents are surfactants with an HLB value greater than or equal to 10. As examples of such inverting agents, mention may be made of ethoxylated sorbitan esters such as sorbitan oleate ethoxylated with 20 equivalents of ethylene oxide (EO20), sorbitan laurate polyethoxylated with 20 mol of ethylene oxide, castor oil polyethoxylated with 40 mol of ethylene oxide, decaethoxylated oleodecyl alcohol, heptaethoxylated lauryl alcohol or sorbitan monostearate polyethoxylated with 20 mol of ethylene oxide. The inverting agent may also be a polyoxyethylenated alkylphenol, polyoxyethylenated (10 mol) cetyl ether, polyoxyethylenated alkylaryl ether, a quaternary ammonium derivative, potassium oleate, N-cetyl-N-ethylmorpholinium ethosulfate, sodium lauryl sulfate, a condensation product of a higher fatty alcohol with ethylene oxide, such as the reaction product of oleyl alcohol with 10 ethylene oxide units, a condensation product of an alkylphenol with ethylene oxide, such as the reaction product of isooctylphenol with 12 ethylene oxide units, a condensation product of an amine of a higher fatty acid with 5 or more ethylene oxide units, tristerylphenol ethylene oxide, an ethylene oxide condensation product of a partial higher fatty ester of a polyhydric alcohol and its internal anhydride (e.g., anhydrous mannitol and anhydrous sorbitol), an amine oxide, an alkyl polyglucoside, a glucamide, a phosphate ester or an alkylbenzene sulfonate, a water-soluble polymeric surfactant.

[0139] In a preferred embodiment, the inverting agent is an ethoxylated nonylphenol, preferably having 4 to 10 ethoxylation, an ethoxy / propoxy alcohol, preferably having C12 to C25 ethoxy / propoxylation, or an ethoxylated tridecyl alcohol, or an ethoxy / propoxy fatty alcohol.

[0140] The inverse emulsion may comprise at least two inverting agents, preferably at least three inverting agents, and even more preferably at least four inverting agents.

[0141] The polymer obtained by inverse emulsion polymerization (HP) is in the form of an inverse emulsion or a powder obtained by drying the inverse emulsion.

[0142] The resulting inverse emulsion can be diluted or concentrated. Dilution is generally achieved by adding water and / or oil to the inverse emulsion. The resulting emulsion can be concentrated, for example by distillation. In that case, a partially dehydrated inverse emulsion is obtained.

[0143] The product can be concentrated by removing all or part of the water and components of the lipophilic phase, such as light oils, generally by distillation under reduced pressure.

[0144] The inverting agent, or mixture of inverting agents, may be added after the distillation, i.e. at the very end of the process.

[0145] According to this third aspect of the invention, the polymer (HP) is in the form of an inverse emulsion. When the polymer (HP) is structured or crosslinked in aqueous droplets emulsified in a lipophilic phase, the polymer (HP) is in the form of a microgel dispersed in the lipophilic phase. This also includes a hybrid polymer dispersed in the main lipophilic phase. When the inverse emulsion is used in an aqueous phase, the hybrid polymer is dispersed in the main aqueous phase.

[0146] The inverse emulsion polymer (HP) obtained by inverse emulsion polymerization according to the invention comprises preferentially from 10% to 70% by weight, and preferentially from 30% to 60% by weight, of hybrid polymer (HP) relative to the total weight of the inverse emulsion.

[0147] Advantageously, the inverse emulsion comprises at least one hybrid polymer (HP), water (generally 10% to 50% by weight), an inert hydrophobic liquid (generally 5% to 50% by weight), at least one surfactant (generally 1% to 10% by weight), and at least one inversion agent (generally 1% to 10% by weight). The inverse emulsion polymer (HP) obtained by inverse emulsion polymerization according to the invention can be dried to obtain a powder. One particularly advantageous drying method is spray drying.

[0148] In this third aspect of the invention, the same factors as those described above, including their preferences, are again used: the nature of the polymerization initiator, the amount of said initiator, the nature of the structure and / or crosslinking agent, the amount of these said structure and / or crosslinking agent, the molecular weight of the resulting polymer (HP), the free radical polymerization, the structure (linear, structured, etc.) of the hybrid polymer (HP).

[0149] Hybrid polymers (HP) obtained by free radical gel polymerization According to a fourth aspect of the present invention, a hybrid polymer (HP) can be prepared by the following sequential steps: (A) preparing an aqueous solution containing 10% to 40% by weight of at least one monomer containing at least one unsaturated ethylenic functional group, and 1% to 30% by weight of at least one protein, water, and optionally at least one pH adjuster; (B) initiating radical polymerization in aqueous solution to obtain a hybrid polymer (HP) in the form of a gel; (C) crushing and drying the resulting gel to obtain a hybrid polymer (HP) in powder form; The gel is obtained by a free radical gel polymerization method comprising:

[0150] The protein is selected with the same preference from those described above. The monomer containing at least one ethylenically unsaturated functional group is selected with the same preference from those containing at least one ethylenically unsaturated functional group described above.

[0151] Prior to step (B), the aqueous solution is generally degassed, for example with nitrogen, to minimize the presence of dioxygen in the aqueous solution. During step (B), one or more polymerization initiators are added. The same polymerization initiators as those described above can be used in the same amounts.

[0152] Steps (A) and (B) are preferentially carried out in the same reactor, called the polymerization reactor.

[0153] In a preferred embodiment, the gel obtained in step (B) is aged at a final polymerization temperature of 80°C to 150°C for at least 60 minutes without heating.

[0154] According to this embodiment, the gel obtained in step (B) before being crushed and dried comprises 10% to 70% by weight, preferentially 20% to 60% by weight, and even more preferentially 30% to 55% by weight of hybrid polymer (HP).

[0155] The gel thus obtained is generally transported to a granulator and chopped, which is then dried, crushed and sieved to obtain the hybrid polymer (HP) in powder form.

[0156] The pH regulator is advantageously chosen from the following elements: hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, citric acid, formic acid, acetic acid, adipic acid, propionic acid, oxalic acid, benzoic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate. The skilled person will know how to define the pH to be reached at the end of step b), as well as the amount and choice of pH regulator, depending on the chemical nature of the polymer to be synthesized, and in particular the nature of the monomers (cationic, anionic, etc.).

[0157] As soon as the polymerization begins, depending on the initiation conditions selected, the aqueous solution heats up or warms up (exothermic reaction). Advantageously, due to the heat of polymerization released, the temperature of the reaction mixture generally rises to between 80° C. and 150° C., preferably between 80° C. and 100° C. The polymerization is advantageously carried out at atmospheric pressure.

[0158] The reactors used are most often jacketed so that the reaction mixture can be cooled or heated as needed. Once the polymerization reaction is complete, the resulting gel can be rapidly cooled, for example, by cooling the walls of the reactor.

[0159] After the polymerization reaction is complete and the gel is allowed to age for at least 60 minutes, the product resulting from the polymerization is a "free-standing" viscous gel.

[0160] Granulation consists in cutting the gel into small pieces. Advantageously, the average size of these gel pieces is less than 1 cm, more advantageously between 4 and 8 mm. A person skilled in the art will know how to select the appropriate means for optimal granulation. Granulation is also described in the section presenting the prior art.

[0161] The drying means and its conditions (duration + temperature) are a matter of routine choice for those skilled in the art. Industrially, drying is carried out by fluidized bed or rotor dryers, advantageously using air heated to temperatures between 70°C and 200°C, the temperature of the air being a function of the nature of the product and the drying time applied.

[0162] At the end of drying, the composition is in physical powder form, which is then crushed and sieved.

[0163] The grinding process consists in breaking down large polymer particles into smaller particles. This can be done by shearing or by mechanically crushing the particles between two hard surfaces. Various types of equipment known to those skilled in the art can be used for this purpose. For example, mention can be made of rotor mills, in which the particles are crushed on a compressing blade by a rotating part, or roll mills, in which the particles are crushed between two rotating cylinders. Sieving, in this case, is intended to remove particles with an average size that is too small or too large, depending on the specifications.

[0164] The hybrid polymer (HP) obtained by gel polymerization may be a water-swellable polymer or a superabsorbent, if the hybrid polymer (HP) is structured or crosslinked with one or more structural and / or crosslinking agents.

[0165] In this fourth aspect of the invention, the same factors as those described above, including their preferences, are again used: the nature of the polymerization initiator, the amount of said initiator, the nature of the structure and / or crosslinking agent, the amount of these said structure and / or crosslinking agent, the molecular weight of the resulting polymer (HP), the free radical polymerization, the structure (linear, structured, etc.) of the hybrid polymer (HP). Use of Hybrid Polymers (HP) in various applications

[0166] In a fifth aspect, the present invention relates in particular to the use of hybrid polymers (HP) as viscosity modifiers. This aspect of the invention also relates to the use of hybrid polymers (HP) according to the invention in various compositions, to the use of hybrid polymers (HP) as viscosity modifiers, to compositions comprising at least one hybrid polymer (HP) according to the invention, and to methods of using said compositions.

[0167] Said use relates to a hybrid polymer (HP) according to the first aspect of the invention, or obtained according to the second aspect of the invention (by free radical polymerization), or obtained according to the third aspect of the invention (by inverse emulsion polymerization), or obtained according to the fourth aspect of the invention (by gel polymerization).

[0168] The present invention therefore relates to the use of said hybrid polymers (HP) as viscosity modifiers in the recovery of hydrocarbons (oil and / or gas), in the drilling and cementing of wells, in the treatment of water in open, closed or semi-closed circuits, in the treatment of fermentation must, in the treatment of sludge, in papermaking, in construction, in the treatment of wood, in the treatment of hydraulic compositions (concrete, cement, mortar and aggregates), in mining, in the formulation of cosmetics, in the formulation of detergents, in the manufacture of textile printing pastes, in the manufacture of battery components, in geothermal applications, in the manufacture of diapers or in agriculture.

[0169] Advantageously, the present invention relates to the use of a hybrid polymer (HP) according to the invention in the preparation of a cosmetic composition as a thickener (thickening agent), conditioner (conditioning agent), stabilizer (stabilizing agent), emulsifier (emulsifying agent), fixative (fixing agent) or film former (film-forming agent).

[0170] The present invention also relates to the use of hybrid polymers (HP) as viscosity modifiers for pigment compositions used in textile printing, said agent comprising at least one hybrid polymer according to the invention.The present invention also relates to the use of polymers (HP) according to the invention as superabsorbents.

[0171] The hybrid polymers (HP) according to the present invention may be used as flocculants, coagulants, binders, fixatives, viscosity reducers, thickeners, absorbents, friction reducers, dewatering agents, drainage aids, filler retention agents, dewatering agents, conditioning agents, stabilizers, film formers, sizing agents, superplasticizers, clay inhibitors or dispersants. The present invention also relates to viscosity modifiers comprising at least one hybrid polymer (HP) according to the present invention in the fields selected from hydrocarbon recovery, well drilling and cementing, hydrocarbon well stimulation, papermaking, construction, mining, cosmetic formulations, detergent formulations, textile manufacturing.

[0172] Due to the wide range of possible applications of the composition, it is used in a variety of compositions.The present invention also relates to an aqueous composition comprising at least one hybrid polymer (HP) according to the invention, preferentially for thickening the composition.

[0173] The hybrid polymers (HP) according to the invention can thicken, solidify, bind, fix, reduce viscosity, provide absorbency, reduce friction, remove water, drain, retain, dehydrate, condition, stabilize, fix, film-form or size aqueous compositions depending on the intended field of application.

[0174] The implementation of the compositions according to the invention in compositions may be carried out in accordance with the knowledge and practice of the formulator, according to the intended field of application.

[0175] Advantageously, the composition according to the invention comprises between 0.001% and 5% by weight of the composition relative to the total weight of the formulation.

[0176] More specifically, the compositions can be used in fields selected from hydrocarbon recovery, well drilling and cementing, hydrocarbon well stimulation, water treatment, fermentation must treatment, sludge treatment, papermaking, construction, wood treatment, hydraulic composition treatment, mining, cosmetic formulation, detergent formulation, textile manufacturing, battery component manufacturing, geothermal applications, diaper manufacturing, or agriculture.

[0177] The invention also relates to the use of such compositions in fields selected from hydrocarbon recovery, well drilling and cementing, hydrocarbon well stimulation, water treatment, fermentation must treatment, sludge treatment, papermaking, construction, wood treatment, hydraulic composition treatment, mining, cosmetic formulation, detergent formulation, textile manufacturing, battery component manufacturing, geothermal applications, diaper manufacturing, or agriculture.

[0178] The present invention also relates to a method for the enhanced recovery of oil or gas by flushing subterranean formations, comprising the use of at least one hybrid polymer (HP) according to the present invention. [Example]

[0179] The advantages of the present invention can best be illustrated in a clear and non-limiting manner by the examples that follow.

[0180] I - Preparation of polymers in inverse emulsion

[0181] Example 1 (Invention): Synthesis of hybrid polymer HP1 in inverse emulsion The aqueous phase is prepared using 24.16% by weight sodium acrylate, 2.68% by weight whey protein powder, 73.11% by weight deionized water, 0.04% by weight Versenex 80, and 0.006% by weight azo initiator. The pH is adjusted to 7.0±0.1.

[0182] The lipophilic phase is prepared using 40.52% by weight of heavy oil (octyldodecyl myristate), 44.78% by weight of light oil (Isopar J), and the following surfactants: 4.90% by weight of Witcamide® 511 (tall oil fatty acid diethanolamine), 1.96% by weight of sorbitan monooleate VG, and 7.84% by weight of HYPERMER 6212.

[0183] The aqueous phase is added to the lipophilic phase with mixing to form an emulsion. The resulting dispersion is allowed to stabilize at 25°C while nitrogen is bubbled through it for 30 minutes, at which point 10 mL of a 0.002 wt% tert-butyl hydroperoxide emulsion and 10 mL of a 0.04 wt% sodium metabisulfite (MBS) emulsion are introduced into the dispersion at a flow rate of 0.1 mL per minute. The polymerization temperature is controlled between 38°C and 42°C for approximately 90 minutes. Residual monomer is scavenged by introducing a 0.03 wt% sodium metabisulfite (MBS) solution at a flow rate of 1.0 mL per minute.

[0184] The water-in-oil emulsion is then filtered using a 300 μm filter and then distilled under reduced pressure at 250 mbar to 80 mbar and 95° C. for 1 hour 30 minutes.

[0185] A water-in-oil hybrid polymer emulsion is obtained.

[0186] 4.5% by weight of an inverting agent (ethoxylated fatty alcohol: TO06) is added to the water-in-oil polymer emulsion.

[0187] Example 2 (Invention): Synthesis of hybrid polymer HP2 in inverse emulsion. An aqueous phase is prepared using 4.21 wt. % acrylamide, 45.79 wt. % acrylamido 2-(acryloyloxy)ethyl trimethylammonium chloride solution, 5.55 wt. % whey protein powder, 44.42 wt. % deionized water, and 0.03 wt. % azo initiator.

[0188] The pH is adjusted to 6.5±0.1.

[0189] The lipophilic phase is prepared from 58.95% by weight of heavy oil (octyldodecyl myristate), 28.10% by weight of light oil (Isopar J), and the following surfactants: 4.02% by weight of Witcamide® 511 (tall oil fatty acid diethanolamine), 1.79% by weight of sorbitan monooleate VG, and 7.14% by weight of HYPERMER 6212.

[0190] The aqueous phase is added to the lipophilic phase with mixing to form an emulsion.

[0191] The resulting dispersion is bubbled with nitrogen for 30 minutes while the temperature stabilizes at 25°C, at which point 0.004% by weight peroxide is added to the emulsion and 10 ml of a solution containing 0.04% by weight sodium metabisulfite emulsion is introduced into the dispersion at a flow rate of 10 milliliters per hour.

[0192] The polymerization temperature is controlled at 38°C to 42°C for about 90 minutes.

[0193] The water-in-oil emulsion is then filtered using a 300 μm filter and then distilled under reduced pressure at 250 mbar to 80 mbar and 90° C. for 1 hour 30 minutes.

[0194] A water-in-oil hybrid polymer emulsion is obtained.

[0195] 4.5 wt % of a high HLB surfactant (TO06) is added to the water-in-oil polymer emulsion.

[0196] (Counterexample): Synthesis of polymer P3 in inverse emulsion. The same protocol as in Example 2 was applied, but the protein was removed from the formulation.

[0197] Example 3 Viscosity measurement Brookfield viscosity is measured on 1.5 wt% aqueous solutions of the hybrid polymer using a Brookfield RVT unit viscometer at 25° C. and a rotation speed of 20 rpm. Table 1 summarizes the results.

[0198] [Table 1]

[0199] The hybrid polymer PH2 exhibits a much higher viscosity in water at 1.5% than that of polymer P3.

[0200] In this case, the Applicant has therefore observed that incorporating serum proteins into this type of emulsion is highly advantageous for improving the viscosity-modulating performance of the hybrid polymer according to the invention.

[0201] II - Synthesis of the hybrid polymers according to the invention by the gel method

[0202] Example 4 (Invention): Synthesis of hybrid polymer PH4 by gel method 45 g of serum protein is slowly added to an aqueous solution containing 550 g of deionized water, 310 g of acrylamido 2-(acryloyloxy)ethyl trimethylammonium chloride (ADC), and 95 g of acrylamide.

[0203] This aqueous solution is placed in a 2 L beaker, cooled to 0°C, and then placed in a Dewar flask.

[0204] The aqueous solution is homogenized for 15 seconds using a hand blender at a speed of 500 rpm, and then degassed under nitrogen bubbling for 15 minutes. Next, the following is added to the aqueous solution: 0.5 g of azo initiator (V50) and 0.003 g of transfer agent (sodium hypophosphite), and then 2.6 × 10 -4 The reaction is initiated by the sequential addition of 1 g of tert-butyl hydroperoxide followed by 1 g of sodium bisulfite. For a final temperature of 94°C, the reaction time is 60 minutes.

[0205] The resulting hybrid polymer PH4 is in the form of a gel, which can be granulated and dried overnight in an air stream at 70°C. The dried granules of polymer PH4 are then milled.

[0206] The resulting polymer PH4 is 100% water soluble and has a UL viscosity of 5g / l = 2.96cPs and an LVT unit of 60 rpm at 25°C?

[0207] Example 5 (This invention): Application test of PH4 Flocculation test on sludge from the Andrézieux wastewater treatment plant with a solids content of 12.2 g / l: To compare the effectiveness of polymer PH4, a flocculation test was carried out with a reference polymer.

[0208] The polymers are tested at a concentration of 3 g / l in deionized water.

[0209] A clumping test is carried out in a beaker to assess the quality of clumping and the amount of water drained after 10 seconds. Table 2 summarizes the results.

[0210] [Table 2]

[0211] Applicants have observed that polymer PH4 achieves similar application performance qualities as the reference polymer at similar dosages.

[0212] Drainage test: 5 ml of a solution containing 3 g / l of the polymer to be tested (Polymer PH4, Reference Polymer 1, Reference Polymer 2) is added to a 400 ml beaker containing 200 ml of sludge, after which the solution is mixed by decanting until flocculation occurs.

[0213] Place the filter cloth in a 90 mm diameter Büchner funnel and wet the entire assembly. Place the Büchner funnel under the graduated cylinder.

[0214] The flocculated sludge solution is poured into the Buchner funnel and a stopwatch is started.

[0215] The volume expelled after 5 and 10 seconds is recorded.

[0216] For a volume of 5 ml drawn from a 3 g / l polymer solution, the results are summarized in Table 3.

[0217] [Table 3]

[0218] Drainage corresponds to the volume of water collected in a given time; the higher the value, the better the polymer performs.

[0219] Applicant has observed that polymer PH4 is a better flocculant than the reference polymer.

[0220] Example 6 (Invention): Synthesis of hybrid polymer PH5 by gel method 140 g of serum protein and 10 g of cross-linking agent (methylenebisacrylamide) are slowly added to an aqueous solution containing 670 g of deionized water, 125 g of potassium acrylate, and 200 g of acrylamide.

[0221] This aqueous solution is placed in a 2 L beaker, cooled to 0°C, and then placed in a Dewar flask.

[0222] The aqueous solution is homogenized using a hand blender at a speed of 500 rpm for 15 seconds and then degassed under nitrogen bubbling for 10 minutes.

[0223] The following is then added to the aqueous solution: 0.21 g sodium persulfate, 0.15 g sodium metabisulfite (MBS), and 0.01 g Mohr's salt. For a final temperature of 94° C., the reaction time is 60 minutes.

[0224] The resulting hybrid polymer PH5 is in the form of a gel, which is then aged for 2 hours. It can then be granulated and dried overnight in an air stream at 70°C. The dried granules of polymer PH5 are then crushed.

[0225] Example 7 (This invention): PH5 application test PH5 water swelling applications Case 1) 0.5g of PH5 powder is added to 750ml of deionized water.

[0226] Mixing is carried out in a 20 cm diameter stainless steel rotating drum under a fume hood for 3 hours.

[0227] Case 2) 0.5g of PH5 powder is added to 750ml of municipal water.

[0228] Mixing is carried out in a 20 cm diameter stainless steel rotating drum under a fume hood for 3 hours.

[0229] In both cases, the entire mixture was placed on a screen with a mesh size of 100 μm and subjected to a 1.5 mm / g (1 g = 9.81 m / s2 ) for 1 minute (Retsch AS 200 Control sieve).

[0230] The product retained by the filter is weighed to give the absorption rate.

[0231] Table 4 summarizes the results.

[0232] [Table 4]

[0233] Polymer PH5 has a similar retention to the reference polymer.

Claims

1. A hybrid polymer (HP) comprising monomer units of at least one monomer containing at least one unsaturated ethylenic functional group and protein units, characterized in that the monomer units and the protein units are partially or entirely linked by at least one covalent bond, and the mass ratio of the monomer units to the protein units is 50 / 1 to 1 / 5.

2. The following sequential steps: (A) preparing a mixture (M1) comprising at least one monomer containing at least one unsaturated ethylenic functional group, and 0.1% to 50% by weight of at least one protein, and optionally at least one solvent; (B) initiating polymerization of the mixture (M1) to obtain at least one hybrid polymer (HP); Hybrid polymers (HP) obtained by a free radical polymerization method comprising:

3. The following sequential steps: (A1) preparing an aqueous phase comprising 1% to 50% by weight of at least one protein, 4% to 40% by weight of at least one monomer containing at least one unsaturated ethylenic functional group, and 20% to 95% by weight of water; (A2) preparing a lipophilic phase comprising 70% to 99% by weight of an inert hydrophobic liquid and 1% to 20% by weight of at least one surfactant; (A3) mixing the aqueous phase with the lipophilic phase to form an inverse emulsion; (B) polymerizing the inverse emulsion to obtain an inverse emulsion hybrid polymer (HP); 3. The hybrid polymer (HP) according to claim 2, obtained by free radical inverse emulsion polymerization by a process comprising:

4. 4. Hybrid polymer (HP) according to any one of claims 1 to 3, characterized in that the monomer units of the at least one monomer comprising at least one unsaturated ethylenic functional group or the at least one monomer comprising at least one unsaturated ethylenic functional group are hydrophilic, nonionic and / or anionic and / or cationic.

5. 5. Hybrid polymer (HP) according to any one of claims 1 to 4, characterized in that the monomer units of the at least one monomer comprising at least one unsaturated ethylenic functional group or the at least one monomer comprising at least one unsaturated ethylenic functional group are selected from acrylamide, acrylic acid, acrylic acid oligomers, 2-acrylamido-2-methylpropanesulfonic acid (ATBS) and / or its salts, N-vinylformamide (NVF), N-vinylpyrrolidone (NVP), dimethyldiallylammonium chloride (DADMAC), quaternized dimethylaminoethyl acrylate (ADAME), quaternized dimethylaminoethyl methacrylate (MADAME).

6. Hybrid polymer (HP) according to any one of claims 1 to 5, characterized in that the protein unit or at least one protein is a plant and / or animal protein.

7. 7. Hybrid polymer (HP) according to any one of claims 1 to 6, characterized in that the protein unit or at least one protein is casein, a serum protein or a wheat protein.

8. Hybrid polymer (HP) according to any one of claims 1 to 7, characterized in that it has a weight average molecular weight of 20,000 to 20,000,000 Daltons.

9. Hybrid polymer (HP) according to any one of claims 1 to 8, characterized in that the polymer is in the form of an inverse emulsion.

10. 10. Use of a hybrid polymer (HP) according to any one of claims 1 to 9 as a flocculant, coagulant, binder, fixative, viscosity reducer, thickener, absorbent, friction reducer, water removal agent, drainage aid, filler retention agent, dewatering agent, conditioning agent, stabilizer, film former, sizing agent, superplasticizer, clay inhibitor or dispersant.

11. 10. Use of the hybrid polymer (HP) according to any one of claims 1 to 9 in a field selected from hydrocarbon recovery, drilling and cementing wells, stimulation of hydrocarbon wells, water treatment, treatment of fermentation must, treatment of sludge, paper making, construction, wood treatment, treatment of hydraulic compositions, mining, cosmetic formulation, detergent formulation, textile manufacturing, manufacturing of battery components, geothermal applications, diaper manufacturing, or agriculture.

12. 10. An aqueous composition comprising at least one hybrid polymer (HP) according to any one of claims 1 to 9, wherein the aqueous composition comprises 0,001% to 5% by weight of said hybrid polymer (HP).

13. 13. Use of the composition of claim 12 in a field selected from hydrocarbon recovery, well drilling and cementing, hydrocarbon well stimulation, water treatment, fermentation must treatment, sludge treatment, papermaking, construction, wood treatment, hydraulic composition treatment, mining, cosmetic formulation, detergent formulation, textile manufacturing, battery component manufacturing, geothermal applications, diaper manufacturing, or agriculture.

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