Injectable solution at ph 7 comprising at least one basal insulin having a pi of between 5.8 and 8.5 and a copolyamino acid carrying carboxylate charges and hydrophobic radicals

Abstract

The invention relates to physically stable compositions in the form of an injectable aqueous solution, the pH of which is between 6.0 and 8.0, and comprising at least: a) one basal insulin whose isoelectric point (pI) is between 5.8 and 8.5, and b) a copolyamino acid carrying carboxylate charges and at least one hydrophobic radical.

Description

INJECTABLE SOLUTION AT PH 7 COMPRISING AT LEAST ONE BASAL INSULIN WITH A PI BETWEEN 5.8 AND 8.5 AND A CHARGE-BEARING CO-POLYAMINOACID CARBOXYLATES AND HYDROPHOBIC RADICALS

[0001] The invention relates to insulin injection therapies for treating diabetes.

[0002] The invention relates to physically stable compositions in the form of an injectable aqueous solution, having a pH between 6.0 and 8.0, comprising at least one basal insulin having an isoelectric point (pi) between 5.8 and 8.5 and a co-polyamino acid carrying carboxylate charges and hydrophobic radicals.

[0003] Insulin therapy, or diabetes therapy by insulin injection, has seen remarkable progress in recent years thanks in particular to the development of new insulins offering better correction of patients' blood glucose compared to human insulin and which allow for better simulation of the physiological activity of the pancreas.

[0004] When a patient is diagnosed with type 2 diabetes, a gradual treatment plan is implemented. Initially, the patient takes oral antidiabetic drugs (OADs) such as metformin. When OADs alone are no longer sufficient to regulate blood glucose levels, a change in treatment must be made, and depending on the patient's specific needs, different treatment combinations may be used. For example, the patient may initially receive basal insulin such as insulin glargine or insulin detemir in addition to OADs, and then, depending on the progression of the disease, a combination of basal and prandial insulin.

[0005] Furthermore, today, to ensure the transition from treatments by DAOs, when these are no longer able to control the level of glucose in the blood, to a basal insulin / prandial insulin treatment, the injection of GLP-1 RA analogues is recommended.

[0006] GLP-1 RAs, for Glucagon-Like Peptide-1 receptor agonists, are insulinotropic peptides or incretins, and belong to the family of gastrointestinal hormones (or Gut Hormones) which stimulate insulin secretion when blood glucose is too high, for example after a meal.

[0007] Gastrointestinal hormones (Gut hormones) are also called satiety hormones. They include, in particular, GLP-1 RA (glucagon-like peptide-1 receptor agonist) and GIP (glucose-dependent insulinotropic peptide), oxyntomodulin (a proglucagon derivative), peptide YY, amylin, cholecystokinin, pancreatic polypeptide (PP), ghrelin, and enterostatin, which have peptide or protein structures. They also stimulate insulin secretion in response to glucose and fatty acids and are therefore potential candidates for the treatment of diabetes.

[0008] Among these, GLP-1 RAs have yielded the best results to date in drug development. They have enabled patients with type 2 diabetes to lose weight while achieving better blood sugar control.

[0009] Analogues or derivatives of GLP-1 RA have thus been developed, in particular to improve their stability.

[0010] On the other hand, to cover his daily insulin needs, a diabetic patient currently has, schematically, two types of insulins with complementary actions: prandial insulins (or so-called rapid-acting insulins) and basal insulins (or so-called slow-acting insulins).

[0011] Prandial insulins allow for rapid management (metabolism and / or storage) of glucose obtained from meals and snacks. The patient must inject a prandial insulin before each meal or snack, approximately 2 to 3 injections per day. The most commonly used prandial insulins are: recombinant human insulin, NovoLog® (aspart insulin from NOVO NORDISK), Humalog® (lispro insulin from ELI LILLY), and Apidra. ® (insulin glulisine from SANOFI).

[0012] Basal insulins maintain the patient's blood glucose homeostasis between meals. They primarily work by blocking the endogenous production of glucose (hepatic glucose). The daily dose of basal insulin generally corresponds to 40-50% of the total daily insulin requirement. Depending on the basal insulin used, this dose is administered in one or two injections, evenly spaced throughout the day. The most commonly used basal insulin is Levemir. ® (insulin detemir from NOVO NORDISK) and Lantus ® (insulin glargine from SANOFI).

[0013] To be exhaustive, it should be noted that NPH (insulin NPH stands for Neutral Protamine Hagedorn; Humulin NPH) ® Insulatard ® ) is the oldest insulin Basal. This formulation results from the precipitation of human insulin (anionic at neutral pH) by a cationic protein, protamine. The microcrystals thus formed are dispersed in an aqueous suspension and dissolve slowly after subcutaneous injection. This slow dissolution ensures a prolonged release of insulin. However, this release does not guarantee a constant insulin concentration over time. The release profile is bell-shaped and lasts only between 12 and 16 hours. It is therefore injected twice a day. This basal N-PH insulin is much less effective than modern basal insulins, such as Levemir. ® and Lantus ® NPH is a basal insulin with intermediate action.

[0014] The principle of NPH has evolved with the advent of rapid-acting insulin analogs, resulting in products called "Premix" offering both rapid and intermediate action. NovoLog Mix® (NOVO NORDISK) and Humalog Mix® (ELI LILLY) are formulations containing a rapid-acting insulin analog, Novolog ® and Humalog®, partially complexed with protamine. These formulations thus contain microcrystals of intermediate-acting insulin analog and a portion of soluble insulin with a rapid action. These formulations offer the advantage of rapid-acting insulin, but they also have the drawback of NPH insulin, i.e., a limited duration of action of between 12 and 16 hours and insulin released in a "bell-shaped" pattern. However, these products allow the patient to inject a basal intermediate-acting insulin with a prandial rapid-acting insulin in a single dose. Many patients are concerned about reducing the number of injections they require.

[0015] Currently marketed basal insulins can be classified according to the technical solution that achieves prolonged action, and to date two approaches are used.

[0016] The first mechanism of action, that of insulin detemir, is its binding to albumin in vivo. It is an analog, soluble at pH 7, which includes a fatty acid side chain (tetradecanoyl) attached at position B29, which, in vivo, allows this insulin to bind to albumin. Its prolonged action is primarily due to this affinity for albumin after subcutaneous injection.

[0017] However, its pharmacokinetic profile does not allow it to cover a day, which means that it is most often used in two injections per day.

[0018] Another insulin that is soluble at pH 7 is insulin degludec, marketed under the name Tresiba. ®dIt also includes a fatty acid side chain attached to insulin (hexadecandioyl-yl-Glu).

[0019] The second, that of insulin glargine, is precipitation at physiological pH. Insulin glargine is an analog of human insulin obtained by elongating the C-terminal portion of the B chain of human insulin with two arginine residues and substituting the asparagine A21 residue with a glycine residue (US 5,656,722). The addition of two arginine residues was intended to adjust the isoelectric point (pi) of insulin glargine at physiological pH, thus rendering this analog of human insulin insoluble in physiological conditions.

[0020] Therefore, the substitution of GA21 was designed to make insulin glargine stable at acidic pH, thus allowing its formulation as an injectable solution at acidic pH. During subcutaneous injection, the transition of insulin glargine from an acidic pH (pH 4-4.5) to a physiological pH (neutral pH) causes it to precipitate under the skin. The slow redissolution of the insulin glargine microparticles ensures a slow and prolonged action.

[0021] The hypoglycemic effect of insulin glargine is almost constant over a period of 24 hours, which allows most patients to limit themselves to a single injection per day.

[0022] Insulin glargine is considered today to be the most widely used basal insulin.

[0023] However, the necessarily acidic pH of basal insulin formulations, such as insulin glargine, which have an isoelectric point between 5.8 and 8.5, can be a significant drawback. This acidic pH sometimes causes injection pain in patients and, more importantly, prevents formulation with other proteins, particularly prandial insulins, as these are not stable at an acidic pH. The impossibility of formulating a prandial insulin at an acidic pH stems from the fact that, under these conditions, a prandial insulin undergoes a secondary deamidation reaction at position A21, which fails to meet the stability requirements applicable to injectable medications.

[0024] To date, in applications WO 2013 / 021143 Al, WO 2013 / 104861 Al, WO 2014 / 124994 Al and WO 2014 / 124993 Al it has been demonstrated that it was possible to solubilize these basal insulins, of the insulin glargine type whose isoelectric point is between 5.8 and 8.5, at neutral pH, while maintaining a difference in solubility between the in-vitro medium (the container) and the in-vivo medium (under the skin), independently of the pH.

[0025] Application WO 2013 / 104861 Al, in particular, describes compositions in the form of an injectable aqueous solution, having a pH between 6.0 and 8.0, comprising at least (a) a basal insulin having an isoelectric point pi between 5.8 and 8.5 and (b) a carboxylate-charge-bearing co-polyamino acid substituted by hydrophobic radicals.

[0026] These prior art compositions have the major drawback of not being sufficiently stable to meet the specifications applicable to pharmaceutical formulations.

[0027] In the examples in the experimental part of this patent application it is demonstrated that the compositions described in particular in WO 2013 / 104861 Al exhibit unsatisfactory stability over time.

[0028] There is therefore a need to find a solution that allows the solubilization of a basal insulin whose isoelectric point (pi) is between 5.8 and 8.5 while maintaining its basal profile after injection but which also allows to satisfy standard physical stability conditions for insulin-based pharmaceutical products.

[0029] Surprisingly, the applicant found that the co-polyamino acids carrying carboxylate charges and hydrophobic radicals according to the invention make it possible to obtain compositions in the form of solutions which not only meet the requirements described in WO 2013 / 104861 Al but which are also able to confer improved physical stability to said compositions without having to increase the amount of excipients used.

[0030] These previously unattainable performance levels are further maintained when basal insulin with an isoelectric point between 5.8 and 8.5 is combined in the composition with prandial insulin and / or a gastrointestinal hormone.

[0031] Thus, surprisingly, the affinity of the co-polyamino acids according to the invention for insulin glargine has been increased in that it allows for solubilization and stabilization of insulin glargine solutions at a [Hy] / [basal insulin] ratio lower than that of the prior art; these results are also obtained without altering, or even improving, the propensity of insulin glargine to precipitate as demonstrated in the experimental part.

[0032] This improved affinity also makes it possible, in the context of chronic treatments, to limit the level of exposure to said excipients.

[0033] The co-polyamino acids carrying carboxylate charges and hydrophobic Hy radicals according to the invention exhibit excellent resistance to hydrolysis. This can be verified in particular under accelerated conditions, for example by hydrolysis tests at basic pH (pH 12).

[0034] In addition, forced oxidation tests, for example of the Fenton oxidation type, show that co-polyamino acids carrying carboxylate charges and hydrophobic Hy radicals exhibit good resistance to oxidation.

[0035] The invention thus relates to physically stable compositions in the form of an injectable aqueous solution, having a pH between 6.0 and 8.0, comprising at least: a) a basal insulin whose isoelectric point (pi) is between 5.8 and 8.5 and b) a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical of formula X.

[0036] In one embodiment, the invention relates to a composition in the form of an injectable aqueous solution, having a pH between 6.0 and 8.0, comprising at least: a) a basal insulin whose isoelectric point pi is between 5.8 and 8.5; b) a co-polyamino acid bearing carboxylate charges and hydrophobic radicals -Hy, said co-polyamino acid being composed of glutamic or aspartic units and said hydrophobic radicals Hy being of the following formula X: Formula X in which GpR is chosen from among the radicals of formulas VII, VU' or VII": ; GpG and GpH, identical or different, are chosen from the radicals of formulas XI or XI': * - NH - G - NH - * Formula XI Formula GpA is chosen from among the radicals of formula VIII Formula VIII In which A' is chosen from among the radicals of formula VIII', III" or VIH'" Formula VIII' Formula VIII" Formula VIII'" -GpL is chosen from among the radicals of formula XII . r HN * Formula XII, GpC is a radical with formula IX: Formula IX; the * indicate the attachment sites of the different groups linked by amide functions; a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 1, 2 or 3 if a = 1; a' is an integer equal to 1, 2 or 3 b is an integer equal to 0 or 1; c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; d is an integer equal to 0, 1 or 2; if e is different from 0 then at least one of the g, h or I is different from 0; and if a = 0 then 1 = 0; A, Ai, Az and AB, identical or different, are linear or branched alkyl radicals, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring, comprising from 1 to 8 carbon atoms; B is a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising from 1 to 9 carbon atoms or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and 1 to 5 oxygen atoms; Cx is a linear or branched monovalent alkyl radical, possibly including a cyclic portion, in which x indicates the number of carbon atoms and: ■ When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x < 25, ■ When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, • When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, * When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, ■ When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, G is a branched alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid function(s). R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms bearing one or more -CONH2 functions, or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and from 1 to 5 oxygen atoms: the hydrophobic radical(s) -Hy of formula X being linked to the PLG: via a covalent bond between a carbonyl group of the hydrophobic radical -Hy and a nitrogen atom on the PLG, thus forming an amide function resulting from the reaction of an amine group on the PLG and an acid group on the precursor -Hy' of the hydrophobic radical -Hy, and via a covalent bond between a nitrogen atom of the hydrophobic radical -Hy and a carbonyl carried by the PLG thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical -Hy and an acid function carried by the PLG, the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between 0 < M < 0.5; When several hydrophobic radicals are carried by a co-polyamino acid, they are either identical or different. - the degree of DP polymerization in glutamic or aspartic units for PLG chains is between 5 and 250; the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K + .

[0037] The invention also relates to a method for preparing stable injectable compositions.

[0038] The pH of the compositions according to the invention is between 6.0 and 8.0, preferably between 6.6 and 7.8 or even more preferably between 6.8 and 7.6.

[0039] The said co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy is soluble in aqueous solution at pH between 6.0 and 8.0, at a temperature of 25 °C and at a concentration less than 100 mg / ml.

[0040] The said co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy is soluble in aqueous solution at pH between 6.0 and 8.0, at a temperature of 25 °C and at a concentration less than 60 mg / ml.

[0041] The co-polyamino acid is a statistical co-polyamino acid in the chaining of glutamic and / or aspartic units.

[0042] The term "alkyl radical" refers to a carbon chain, linear or branched, which does not include any heteroatoms.

[0043] In the formulas, the * indicate the attachment sites of the different elements represented.

[0044] Physically stable composition means compositions that meet the visual inspection criteria described in the European, American and international pharmacopoeias, i.e. compositions that are clear and do not contain visible particles, but are also colorless.

[0045] The term "injectable aqueous solution" refers to solutions whose solvent is water and which meet the conditions of the EP and US pharmacopoeias.

[0046] The compositions in the form of an injectable aqueous solution according to the invention are clear solutions. A "clear solution" is defined as a composition that meets the criteria described in the American and European Pharmacopoeias concerning injectable solutions. In the US Pharmacopoeia, solutions are defined in Part 1151, which refers to injection. <1> (referring to <788> according to USP 35 and specified in <788> according to USP 35 and in <787> , <788> And <790> USP 38 (from 1 er August 2014), according to USP 38). In the European Pharmacopoeia, injectable solutions must meet the criteria given in sections 2.9.19 and 2.9.20.

[0047] The term "co-polyamino acid consisting of glutamic or aspartic units" refers to non-cyclic linear chains of glutamic acid or aspartic acid units linked together by peptide bonds, said chains having a C-terminal part, corresponding to the carboxylic acid at one end, and an N-terminal part, corresponding to the amine at the other end of the chain.

[0048] The term "soluble" means capable of producing a clear, particle-free solution at a concentration of less than 100 mg / ml in distilled water at 25 °C.

[0049] The radicals Hy, GpR, GpG, GpH, GpA, GpL and GpC are each independently identical or different from residue to residue.

[0050] In one embodiment, the composition according to the invention is characterized in that Hy comprises between 15 and 100 carbon atoms.

[0051] In one embodiment, the composition according to the invention is characterized in that Hy comprises between 30 and 70 carbon atoms.

[0052] In one embodiment, the composition according to the invention is characterized in that Hy comprises between 40 and 60 carbon atoms.

[0053] In one embodiment, the composition according to the invention is characterized in that Hy comprises between 20 and 30 carbon atoms.

[0054] In one embodiment, the composition according to the invention is characterized in that Hy comprises more than 30 carbon atoms.

[0055] In the formulas, the * indicate the attachment sites of hydrophobic radicals to P LG or between the different groups GpR, GpG, GpH, GpA, GpL and GpC to form amide functions.

[0056] The Hy radicals are attached to the PLG via amide functions.

[0057] In one embodiment, r=0 and the hydrophobic radical of formula X is linked to the PLG via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom carried by the PLG, thus forming an amide function resulting from the reaction of an amine function carried by the precursor of the PLG and an acid function carried by the precursor Hy' of the hydrophobic radical.

[0058] In one embodiment, r = l or 2 and the hydrophobic radical of formula X is bonded to the PLG: ■ via a covalent bond between a nitrogen atom of the hydrophobic radical and a carbonyl group on the PLG, thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical and an acid function on the PLG or, • via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom carried by the PLG, thus forming an amide function resulting from the reaction of an acid function of the precursor Hy' of the hydrophobic radical -Hy and an amine function of the PLG.

[0059] In one embodiment, if GpA is a radical of the formula City and r = l, then: The GpCs are linked directly or indirectly to Nai and N2, and the PLG is linked directly or indirectly via GpR to Npi, or 2. The GpCs are linked directly or indirectly to N ai and NPI, and the P LG is linked directly or indirectly via GpR to "2, or The GpCs are linked directly or indirectly to N2 and Npi, and the PLG is linked directly or indirectly via GpR to N a i.

[0060] In one embodiment, if GpA is a radical of the formula City and r=0, then: GpCs are linked directly or indirectly to N aiand N "2 and the PLG is linked directly or indirectly to Npi; or - the GpCs are linked directly or indirectly to N1 and N1, and the PLG is linked directly or indirectly to N2; or GpCs are linked directly or indirectly to N a 2 and Npi, and the PLG is linked directly or indirectly to N ai .

[0061] In one embodiment, if GpA is a radical of formula VUId and r=l, then GpCs are linked directly or indirectly to N a i, N'2 and Npi and the PLG is linked directly or indirectly via GpR to Np; or GpCs are linked directly or indirectly to IM a i, Na2 and Np2 and PLG is linked directly or indirectly via GpR to Npi; or GpCs are linked directly or indirectly to N a i, Npi and Np2 and the PLG is linked directly or indirectly via GpR to Noi; or GpC is linked directly or indirectly to IM "2, IMpi and Np and PLG is linked directly or indirectly via GpR to Nai.

[0062] In one embodiment, if GpA is a radical of formula VUId and r=0, then GpCs are linked directly or indirectly to N a i, N CÛ and Npi and the PLG is linked directly or indirectly to Np; or The GpCs are linked directly or indirectly to Nai, N a 2 and Np2 and the PLG is linked directly or indirectly to Np1; or GpCs are linked directly or indirectly to N a i, Npi and Np2 and the PLG is linked directly or indirectly to I 0. ; or GpCs are linked directly or indirectly to N a 2, Npi and Np and the PLG is linked directly or indirectly to N ai .·

[0063] In one embodiment, when r=2 then the GpR group linked to the PLG is chosen from among the GpRs of formula VII.

[0064] In one embodiment, when r=2 then the GpR group linked to the PLG is chosen from the GpRs of formula VII and the second GpR is chosen from the GpRs of formula VII".

[0065] In one embodiment, when r=2 then the GpR group linked to the P LG is chosen from among the GpRs of formula VU".

[0066] In one embodiment, when r=2 then the GpR group linked to the PLG is chosen from among the GpRs of formula VU" and the second GpR is chosen from among the GpRs of formula VII.

[0067] In one embodiment, a = 0,

[0068] In an embodiment where h = 1 and g = 0,

[0069] In an embodiment h= 0 and g = l,

[0070] In one embodiment, r = 0, g = l and h = 0.

[0071] In one embodiment, at least one of the g, h or I is different from 0.

[0072] In at least one embodiment of g and h is equal to 1.

[0073] In at least one embodiment of g and h is equal to 1.

[0074] In one embodiment a = 1 and I = 1.

[0075] In one embodiment, if I = 0, at least one of the g or h is equal to 0.

[0076] In one embodiment, if I = 1, at least one of the g or h is equal to 0.

[0077] In an embodiment g+h>2.

[0078] In one embodiment g is greater than or equal to 2 (g>2).

[0079] In one embodiment h is greater than or equal to 2 (h>2).

[0080] In one embodiment, g+h>2 and a and I are equal to 0 (a=l=0).

[0081] In one embodiment, g+h>2 and b is equal to 0 (b=0).

[0082] In one embodiment, g or h is greater than or equal to 2 (g>2) and b is equal to 0.

[0083] In one embodiment, g+h ³2, b is equal to 0 (b=0) and e is equal to 1 (e= l).

[0084] In one embodiment g or h is greater than or equal to 2 (g >2) b is equal to 0 (b=0) and e is equal to 1 (e= l).

[0085] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r = 2 of formula Xc', as defined below. Formula Xc' in which GpRi is a radical of formula VII. Formula VII in which GpR, GpG, GpA, GpL, GpH, GpC, R, a, a', g, h, I and G have the definitions given previously.

[0086] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r = 2 of formula Xc', as defined below: Formula Xc' in which GpRi is a radical of formula VU". OO * — URU— * Formula VII" in which GpR, GpG, GpA, GpL, GpH, GpC, R, a, a', g, h, I and G have the definitions given previously.

[0087] In an embodiment g = h = 0, a = 1, GpA is a radical of Formula VIII with s' = 1 and A' of Formula VIH' or VIII", and I = 1.

[0088] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r = 2 of formula Xc', as defined below: Formula Xc' in which GpRi is a radical of formula VII. Formula VII in which GpR, GpG, GpA, GpL, GpH, GpC, R, a, a', g, h, I and I' have the definitions given previously.

[0089] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r = 2 of formula Xc', as defined below: Formula Xc' in which GpRi is a radical of formula VU". in which GpR, GpG, GpA, GpL, GpH, GpC, R, a, a', g, h, I and P have the definitions given previously.

[0090] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which i = o, of formula Xb' as defined below Formula Xb' in which GpR is chosen from among the radicals of formulas VII, VU' or VII": ; GpG is chosen from among the radicals of formula XI or CG: * - NH - G - NH - * Formula XI Formula GpA is chosen from among the radicals of formula VIII in which s' = 1 represented by the Villa formula or of formula VIII in which and s' = 0 represented by the VUIb formula: — * Formula VUIb GpC is a radical with formula IX; Formula IX; the * indicate the attachment sites of the different groups linked by amide functions; a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 1 or a' = 2 if a = 1; a' is an integer equal to 1 or 2 and o if a' is equal to 1 then a is equal to 0 or to 1 and GpA is a radical of formula VlIIb and, o if a' is equal to 2 then a is equal to 1, and GpA is a radical of Villa formula; b is an integer equal to 0 or 1; c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; d is an integer equal to 0, 1 or 2; e is an integer equal to 0 or 1; g is an integer equal to 0, 1, 2, 3, 4, 5 or 6; h is an integer equal to 0, 1, 2, 3, 4, 5 or 6, and at least one of the g or h is different from 0; r is an integer equal to 0, 1, or 2, and s' is an integer equal to 0 or 1; Ai is a linear or branched alkyl radical, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring, comprising from 1 to 6 carbon atoms; B is a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising from 1 to 9 carbon atoms or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and 1 to 5 oxygen atoms; C x is a linear or branched monovalent alkyl radical, possibly including a cyclic part, in which x indicates the number of carbon atoms and: When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x < 25, When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, ■ When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, • When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, • When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, - G is a branched alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid function(s), R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms bearing one or more -CONH2 functions, or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and from 1 to 5 oxygen atoms: - The hydrophobic radical(s) Hy of formula X being linked to PLG: o via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom carried by the PLG thus forming an amide function resulting from the reaction of an amine function carried by the PLG and an acid function carried by the precursor of the hydrophobic radical, and o via a covalent bond between a nitrogen atom of the hydrophobic radical and a carbonyl carried by the PLG, thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical and an acid function carried by the PLG. - the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between 0 < M < 0.5; When several hydrophobic radicals are carried by a co-polyamino acid, they are either identical or different. - the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K + .

[0091] In one embodiment, said at least one hydrophobic radical—Hy is chosen from the radicals of formula X as defined below in which I = 0, -GpA is chosen from the radicals of formula VIII in which s' = 1 and A' is chosen from the radicals of formula VIII" or VIH'", of formula Xb' as defined below: Formula Xb' in which GpR is chosen from among the radicals of formulas VII, VIF or VII": GpG is chosen from among the radicals of formula XI or XI': O * He r H * * - NH - G - NH - * GN Formula XI Formula XI GpA is chosen from among the radical formulas, City or VUId: ormu ee Formula VlIId; GpC is a radical with formula IX: The * indicate the attachment sites of the different groups linked by amide functions; a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 2 or 3 if a = 1; a' is an integer equal to 2 or 3 and o if a' is equal to 1 then a is equal to 0 and, o if a' is equal to 2 or 3 then a is equal to 1, and GpA is a radical of formula Ville or VlIId; b is an integer equal to 0 or 1; - c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; d is an integer equal to 0, 1 or 2; e is an integer equal to 0 or 1; g is an integer equal to 0, 1, 2, 3, 4, 5 or 6; h is an integer equal to 0, 1, 2, 3, 4, 5 or 6, and at least one of the g or h is different from 0; r is an integer equal to 0, 1, or 2, and s' is an integer equal to 1; Ai, A2, A3, identical or different, are linear or branched alkyl radicals, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring, comprising from 1 to 6 carbon atoms; B is a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising from 1 to 9 carbon atoms or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and 1 to 5 oxygen atoms; Cx is a linear or branched monovalent alkyl radical, possibly including a cyclic portion, in which x indicates the number of carbon atoms and: • When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x ≤ 25, ■ When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, • When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, The hydrophobic radical(s) Hy of formula X being linked to PLG: o via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom carried by the PLG thus forming an amide function resulting from the reaction of an amine function carried by the PLG and an acid function carried by the precursor -Hy' of the hydrophobic radical, and o via a covalent bond between a nitrogen atom of the hydrophobic radical and a carbonyl carried by the PLG, thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical and an acid function carried by the PLG. G is a branched alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid function(s), R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms bearing one or more -CONH2 functions, or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and from 1 to 5 oxygen atoms: the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between 0 < M < 0.5; When several hydrophobic radicals are carried by a co-polyamino acid, they are either identical or different. the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K + .

[0092] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which a = 1 and a' = 1 of formula Xa as defined below: Formula Xa in which GpA is a radical of formula VIII and A' is chosen from among the radicals of formula VIII' with s'=0 and GpA is a radical of formula VUIb Formula VUIb And GpR, GpG, GpL, GpH, GpC, Ai, r, g, h, I and G have the definitions given previously.

[0093] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which a = 1 of formula Xb as defined below: Formula Xb in which GpA is a radical of formula VIII and A' is chosen from among the radicals of formula VIII' with s' = 1 and GpA is a radical of Formula Villa Villa Package And GpR, GpG, GpL, GpH, GpC, Ai, a', r, g, h, I and G have the definitions given previously.

[0094] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which a = 1 as defined below: Formula Xb in which GpA is a radical of formula VIII and A is chosen from among the radicals of formula VIII" with s'= l and GpA is a radical of Formula Ville And GpR, GpG, GpL, GpH, GpC, Ai, Ai, r, g, h, a', I and G have the definitions given previously.

[0095] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which a = 1 as defined below: Formula Xb in which GpA is a radical of formula VIII and A is chosen from among the radicals of formula VIII'" with s'= l, and GpA is a radical of formula VIII''' Formula VlIId; And GpR, GpG, GpL, GpH, GpC, Ai, A2, A3, a', r, g, h, I and G have the definitions given previously.

[0096] In one embodiment, the composition according to the invention is characterized in that said hydrophobic radicals are chosen from hydrophobic radicals of formula X in which GpA is a radical of formula VlIIb, a' = 1 and I = 0 represented by the following formula Xe: Formula Xe GpR, GpG, GpA, GpH, GpC, r, g, h, and a have the definitions given previously.

[0097] In one embodiment, r=0, and GpA is chosen from among the radicals of formula Villa and VlIIb.

[0098] In one embodiment, r=0, g=0 and GpA is chosen from the radicals of formula Villa and VlIIb.

[0099] In one embodiment, r=0, GpA is chosen from the radicals of formula Villa and VlIIb and h=0. [000100] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r=l of formula Xc, as defined below: Formula Xc in which GpR is a radical of formula VII. HH * N— R— N * Formula VII And GpG, GpA, GpL, GpH, GpC, R, a, a', g, h, I, a' and G have the definitions given previously. [000101] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r=l of formula Xc, as defined below: Formula Xc in which GpR is a radical of formula VII'. Formula VU' And GpG, GpA, GpL, GpH, GpC, R, a, a', g, h, I, a' and G have the definitions given previously. [000102] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r= l of formula Xc as defined below Formula Xc in which GpR is a radical of formula VU". [000103] In one embodiment, r= l and GpR is chosen from among the radicals of formula VII' or VII" and h = 0. [000104] In one embodiment, r= l, g =0 and GpR is a radical of formula VII' and h = 0. • In one embodiment, r= l, g=0 and GpR is a radical of formula VU' and h = 1. [000105] In one embodiment, r= l, g=0, GpR is a radical of formula VU', GpA is chosen from among the radicals of formula Villa or VUIb and h = 0. [000106] In one embodiment, r- 1, g =0, GpR is a radical of formula VU', GpA is chosen from among the radicals of formula Villa or VUIb and h = 1. [000107] In one embodiment, r= l, g=0, GpR is a radical of formula VU', GpA is a radical of formula Villa and h = 0. [000108] In one embodiment, r= l, g =0, GpR is a radical of formula VU', GpA is a radical of formula Villa and h = 1. [000109] In one embodiment, r= l, g=0, GpR is a radical of formula VII', GpA is a radical of formula VUIb and h = 0. [000110] In one embodiment, r= l, g=0, GpR is a radical of formula VU', GpA is a radical of formula VUIb and h = 1. [000111] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X as defined below: Formula X in which GpC is a radical of formula IX in which e=0 and GpC is a radical of formula IXa Formula IXa [000112] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X as defined below: Formula X in which GpC is a radical of formula IX in which e = l, b = 0 and GpC is a radical of formula IXd Formula IXd [000113] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X as defined below: Formula X in which GpC is a radical of formula IX in which e= l and GpC is a radical of formula IXb Formula IXb [000114] In one embodiment, said at least one hydrophobic radical—Hy is chosen from among the radicals of formula X in which r, g, a, l, h are equal to 0, of formula Xd as defined below: Formula Xd, in which GpC is a radical of formula IX, in which e=0, b=0 and GpC is a radical of formula IXe [000115] In one embodiment, the composition according to the invention is characterized in that said hydrophobic radicals are chosen from hydrophobic radicals of formula X in which a' = 2 and a = 1 and I = 0 represented by the following formula Xf: Formula Xf GpR, GpG, GpA, GpH, GpC, r, g and h have the definitions given previously. [000116] In one embodiment, the composition according to the invention is characterized in that said hydrophobic radicals are chosen from hydrophobic radicals of formula X in which h = 0, I = 0 and I' = 1 represented by the following formula Xg: GpR, GpG, GpA, GpC, r, g, a and a' have the definitions given previously. [000117] In one embodiment, the composition according to the invention is characterized in that said hydrophobic radicals are chosen from hydrophobic radicals of formula X in which h = 0, a' = 1 represented by the following formula Xh: Formula Xh GpR, GpG, GpA, GpC, r, a and g have the definitions given previously. [000118] In one embodiment, the composition according to the invention is characterized in that said hydrophobic radicals are chosen from hydrophobic radicals of formula X in which h = 0, a' = 2 and a = 1 represented by the following formula Xi: Formula Xi GpR, GpG, GpA, GpC, r and g have the definitions given previously. [000119] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent linear alkyl radical comprising from 2 to 12 carbon atoms. [000120] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent alkyl radical comprising from 2 to 6 carbon atoms. [000121] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent linear alkyl radical comprising from 2 to 6 carbon atoms. [000122] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent alkyl radical comprising 2 to 4 carbon atoms. [000123] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent linear alkyl radical comprising 2 to 4 carbon atoms. [000124] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent alkyl radical comprising 2 carbon atoms. [000125] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent linear alkyl radical comprising from 1 to 11 carbon atoms. [000126] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent alkyl radical comprising from 1 to 6 carbon atoms. [000127] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent alkyl radical, comprising from 2 to 5 carbon atoms and bearing one or more amide (-CONH2) functions. [000128] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent linear alkyl radical, comprising from 2 to 5 carbon atoms and bearing one or more amide (-CONH2) functions. [000129] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a radical chosen from the group consisting of the radicals represented by the formulas below: [000130] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a radical of formula XI. [000131] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a radical of formula X2. [000132] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is linked to the co-polyamino acid via an amide function carried by the carbon in the delta or epsilon position (or in position 4 or 5) relative to the amide function (-CONH2). [000133] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is an unsubstituted linear ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms. [000134] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is an ether radical. [000135] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is an ether radical comprising 4 to 6 carbon atoms. [000136] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a divalent alkyl radical comprising 6 carbon atoms. [000137] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is an ether radical represented by the formula [000138] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a polyether radical. [000139] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a linear polyether radical comprising 6 to 10 carbon atoms and 2 to 3 oxygen atoms. [000140] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a polyether radical chosen from the group consisting of the radicals represented by the formulas below: [000141] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a radical of formula X3. [000142] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a radical of formula X4. [000143] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a polyether radical chosen from the group consisting of the radicals represented by the formulas X5 and X6 below: [000144] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a polyether radical of formula X5. [000145] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which R is a polyether radical of formula X6. [000146] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which the GpG and / or GpH radical has the formula CG in which G is an alkyl radical comprising 6 carbon atoms represented by the formula Z below: Formula Z [000147] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which the GpG and / or GpH radical has the formula XI in which G is an alkyl radical comprising 4 carbon atoms represented by the formula Z below: Formula Z' [000148] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which the GpG and / or GpH radical is of formula XI in which G is an alkyl radical comprising 4 carbon atoms represented by -(CH2)2-CH(COOH)-. [000149] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which the GpG and / or GpH radical is of formula XI in which G is an alkyl radical comprising 4 carbon atoms represented by -CH((CH2)2COOH)-. [000150] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which the GpG and / or GpH radical is of formula XI in which G is an alkyl radical comprising 3 carbon atoms represented by -CH2-CH-(COOH). [000151] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which the GpG and / or GpH radical is of formula XI in which G is an alkyl radical comprising 3 carbon atoms represented by -CH(CH2)COOH)-. [000152] Formulas X, Xa, Xb... and GPA In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xe, Xf, Xg, Xh and Xi is a radical in which the GpA radical is of formula VIII and in which Ai, A2 or A3 is chosen from the group consisting of radicals represented by the formulas below: [000153] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which the GpC radical of formula IX is chosen from the group consisting of the radicals of formulas IXe, IXf or IXg shown here: [000154] In one embodiment, the composition is characterized in that the hydrophobic radical of formulas X, Xa, Xb, Xb', Xd, Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which the GpC radical of formula IX is chosen from the group consisting of radicals of formulas IXe, IXf or IXg in which b is equal to 0, corresponding respectively to the formulas IXh, IXi, and IXj shown here: [000155] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which the GpC radical corresponds to the formula IX or IXe in which b = 0, and corresponds to the formula IXh. [000156] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of linear alkyl radicals. [000157] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of branched alkyl radicals. [000158] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of alkyl radicals comprising between 19 and 14 carbon atoms. [000159] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of the radicals represented by the formulas below: [000160] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of alkyl radicals comprising between 15 and 16 carbon atoms. [000161] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of the radicals represented by the formulas below: [000162] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of the radicals represented by the formulas below: [000163] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of alkyl radicals comprising between 17 and 25 carbon atoms. [000164] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of alkyl radicals comprising between 17 and 18 carbon atoms. [000165] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of the alkyl radicals represented by the formulas below: [000166] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of alkyl radicals comprising between 18 and 25 carbon atoms. [000167] In one embodiment, the composition is characterized in that the hydrophobic radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi is a radical in which Cx is chosen from the group consisting of the alkyl radicals represented by the formulas below [000168] In one embodiment, the composition is characterized in that the hydrophobic radical is a radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi in which the GpC radical of formula IX is chosen from the group consisting of radicals in which Cx is chosen from the group consisting of alkyl radicals comprising 14 or 15 carbon atoms. [000169] In one embodiment, the composition is characterized in that the hydrophobic radical is a radical of formula X, Xa, Xb, Xb', Xc, Xd, Xe, Xf, Xg, Xh and Xi, wherein the GpC radical of formula IX is chosen from the group consisting of radicals in which Cx is chosen from the group constituted by the radicals represented by the formulas below: [000170] In one embodiment, when a' = 1, x is between 11 and 25 (11 < x < 25). In particular, when x is between 15 and 16 (x = 15 or 16) then r = 1 and R is an ether or polyether radical, and when x is greater than 17 (x > 17) then r = 1 and R is an ether or polyether radical. [000171] In one embodiment, when a' = 2, x is between 9 and 15 (9 < x < 15). [000172] In one embodiment, the copolyamino acid is chosen from the copolyamino acids of formula XXXb in which the hydrophobic radical -Hy is chosen from the group of hydrophobic radicals of formula X, Xc', Xa, Xb', Xc, Xe, Xg and Xh in which a' = 1 and = 1 and GpC is a radical of formula IXe. [000173] In one embodiment, the copolyamino acid is chosen from the copolyamino acids of formula XXXb in which the hydrophobic radical -Hy is chosen from the group of hydrophobic radicals of formula X, Xc', Xa, Xb', Xc, Xe, Xg and Xh in which a' = 1 and = 1 and GpC is a radical of formula IX in which e=0. [000174] In one embodiment, the copolyamino acid is chosen from the copolyamino acids of formula XXXb in which the hydrophobic radical -Hy is chosen from the group of hydrophobic radicals of formula X, Xc', Xa, Xb, Xc, Xf, Xg and Xi in which a' = 2 or l' = 2 and GpC is a radical of formula IXe. [000175] In one embodiment, the copolyamino acid is chosen from the copolyamino acids of formula XXXb in which the hydrophobic radical -Hy is chosen from the group of hydrophobic radicals of formula X, Xc', Xa, Xb, Xc, Xf, Xg and Xi in which a' = 2 and l' = 2 and GpC is a radical of formula IX in which e = 0. [000176] In one embodiment, the copolyamino acid is chosen from the copolyamino acids of formula XXXa in which the hydrophobic radical -Hy is chosen from the group of hydrophobic radicals of formula X, Xc', Xa, Xb', Xc, Xe, Xg and Xh in which a' = 1 and G = 1 and GpC is a radical of formula IXe. [000177] In one embodiment, the copolyamino acid is chosen from among the copolyamino acids of formula XXXa in which the hydrophobic radical -Hy is chosen in the group of hydrophobic radicals of formula X, Xc', Xa, Xb, Xc, Xf, Xg and Xi in which a' = 2 or l' = 2 and GpC is a radical of formula IXe. [000178] In one embodiment, the hydrophobic radical Hy is chosen from the group of hydrophobic radicals of formula X, in which h is greater than or equal to 2 and GpC is of formula Ixe. [000179] In one embodiment, the hydrophobic radical Hy is chosen from the group of hydrophobic radicals of formula X, in which g is greater than or equal to 2 and a, I and h are equal to 0 and GpC is of formula Ixe. [000180] In one embodiment, the composition is characterized in that the hydrophobic radical is chosen from among the hydrophobic radicals of formula X, Xc', Xa, Xb, Xb', Xc, Xe, Xg and Xh in which a'= l and l'= l and in which Cx is chosen from the group consisting of linear alkyl radicals. [000181] In one embodiment, the composition is characterized in that the hydrophobic radical is chosen from among the hydrophobic radicals of formula X, Xc', Xa, Xb, Xb', Xc, Xf, Xg and Xi in which a'=2 or !'=2 and in which Cx is chosen from the group consisting of linear alkyl radicals. [000182] In one embodiment, the hydrophobic radical -Hy is chosen from the group of hydrophobic radicals of formula X, in which GpR is a radical of formula VII, GpH is a radical of formula XI and GpC is a radical of formula IX in which e= l, b=0 and x= 13. [000183] In one embodiment, the copolyaminoacid is a poly-L-glutamate of sodium modified at one of its ends of the formula shown below described in example Bl. [000184] In one embodiment, the copolyaminoacid is a poly-L-glutamate of sodium modified at one of its ends of the formula shown below described in Example B18. [000185] In one embodiment, the composition according to the invention is characterized in that the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.007 and 0.3. [000186] In one embodiment, the composition according to the invention is characterized in that the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.01 and 0.3. [000187] In one embodiment, the composition according to the invention is characterized in that the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.02 and 0.2. [000188] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.007 and 0.15. [000189] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.01 and 0.1. [000190] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.02 and 0.08. [000191] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 9 and 10 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.03 and 0.15. [000192] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 11 and 12 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.015 and 0.1. [000193] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 11 and 12 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.02 and 0.08. [000194] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 13 and 15 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.01 and 0.1. [000195] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 13 and 15 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.01 and 0.06. [000196] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.007 and 0.3. [000197] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.01 and 0.3. [000198] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.015 and 0.2. [000199] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 11 and 14 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.1 and 0.2. [000200] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 15 and 16 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.04 and 0.15. [000201] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 17 and 18 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.02 and 0.06. [000202] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 19 and 25 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.01 and 0.06. [000203] In one embodiment, the composition according to the invention is characterized in that the hydrophobic radical corresponds to the formula X in which the radical Cx comprises between 19 and 25 carbon atoms and the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0.01 and 0.05. [000204] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the following co-polyamino acids of formula XXXa': formula XXXa in which, D represents, independently, either a -CH2- group (aspartic unit) or a -CH2-CH2- group (glutamic unit), Hy is a hydrophobic radical chosen from among the hydrophobic radicals of formula X, in which r = 1 and GpR is a radical of Formula VII, Ri is a hydrophobic radical chosen from among the hydrophobic radicals of formula X in which r = 0 or r = 1 and GpR is a radical of Formula VII', or a radical chosen from the group consisting of an H, a linear acyl group in C2 to C10, a branched acyl group in C4 to C10, a benzyl, a terminal 'amino acid' unit and a pyroglutamate, R2 is a hydrophobic radical chosen from among the hydrophobic radicals of formula X in which r = 1 and GpR is a radical of Formula VII, or a radical -NR'R", R' and R" identical or different being chosen from the group constituted by H, the linear or branched or cyclic alkyls in C2 to C10, the benzyl and said R' and R" alkyls can together form one or more saturated, unsaturated and / or aromatic carbon rings and / or can include heteroatoms, chosen from the group consisting of O, N and S; X represents a cationic entity chosen from the group comprising alkali cations; n + m represents the degree of polymerization DP of the co-polyamino acid, that is, the average number of monomeric units per co-polyamino acid chain, and 5 < n + m < 250. [000205] When the co-polyamino acid comprises one or more aspartic unit(s), the latter may undergo structural rearrangements. [000206] In one embodiment, the composition according to the invention is characterized in that when the co-polyamino acid comprises aspartate units, then the co-polyamino acid may further comprise monomeric units of formula XXXI and / or XXXI': Formula XXXI Formula CCCG [000207] A co-polyamino acid with statistical grafting is called a co-polyamino acid carrying carboxylate charges and at least one hydrophobic radical, a co-polyamino acid of formula XXXa. [000208] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formulas XXXa', in which Ri = R'i and R2 = R'2, of the following formula XXXa: Formula XXXa in which, m, n, X, D and Hy have the definitions given previously, R'i is a radical chosen from the group consisting of an H, a linear acyl group at C2 with C10, a branched acyl group at C4 with C10, a benzyl, a terminal "amino acid" unit and a pyroglutamate, R'2 is a radical -NR'R", R' and R" identical or different being chosen from the group consisting of H, linear or branched or cyclic alkyls in C2 to C10, benzyl and said R' and R" alkyls being able to form together one or more saturated, unsaturated and / or aromatic carbon rings and / or being able to include heteroatoms, chosen from the group consisting of O, N and S. [000209] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formulas XXXa, in which Hy is a radical of formula X. [000210] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXa, in which Hy is a radical of formula X, in which r= l. [000211] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from co-polyamino acids of formula XXXa, in which Hy is a radical of formula X, in which r= l, and for GpC, b=0. [000212] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from co-polyamino acids of formula XXXa, in which Hy is a radical of formula X and in which GpC is a radical of formula IX. [000213] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXa, in which Hy is a radical of formula X and in which GpC is a radical of formula IX and r= l. [000214] A co-polyamino acid with definite grafting is called a co-polyamino acid carrying carboxylate charges and at least one hydrophobic radical, a co-polyamino acid of formula XXXb. [000215] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXa' in which n = 0 of the following formula XXXb: Formula XXXb in which m, X, D, Ri and R2 have the definitions given previously and at least Ri or R2 is a hydrophobic radical of formula X. [000216] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from co-polyamino acids of formula XXXa' in which n = 0 of formula XXXb and Ri or R2 is a hydrophobic radical of formula X. [000217] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXb, in which RI = R'I, of formula XXXb': Formula XXXb' in which m, X, D, R'i and R2 have the definitions given previously and R2 is a hydrophobic radical of formula X. [000218] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXb, in which R2 = R'2, of formula XXXb": Formula XXXb" in which m, X, D, Ri and R'2 have the definitions given previously and Ri is a hydrophobic radical of formula X. [000219] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from co-polyamino acids of formula XXXb or XXXb" in which Ri is a hydrophobic radical of formula X and GpR is of formula VII'. [000220] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXb or XXXb" in which Ri is a hydrophobic radical of formula X and GpR is of formula VII". [000221] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXb or XXXb" in which Ri is a hydrophobic radical of formula X and GpR is of formula VII' and GpC is of formula IX. [000222] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from co-polyamino acids of formula XXXb or XXXb' in which Ri is a hydrophobic radical of formula X and GpR is of formula VU' and GpC is of formula IX. [000223] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from co-polyamino acids of formula XXXb or XXXb' in which R2 is a hydrophobic radical of formula X in which r = 1 and GpR is of formula VII. [000224] In one embodiment, the composition is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXXa', in which at least one of the Ri or R2 is a hydrophobic radical as defined above, of the following formula XXX: formula XXX in which. D represents, independently, either a -CH2- group (aspartic unit) or a -CH2-CH2- group (glutamic unit), Hy is a hydrophobic radical chosen from among the hydrophobic radicals of formula X, in which r = 1 and GpR is a radical of Formula VII, Ri is a hydrophobic radical chosen from among the hydrophobic radicals of formula X in which r=0 or r=l and GpR is a radical of Formula VII', or a radical chosen from the group consisting of an H, a linear acyl group at C2 to C10, a branched acyl group at C4 to C10, a benzyl, a terminal "amino acid" unit and a pyroglutamate, R2 is a hydrophobic radical chosen from among the hydrophobic radicals of formula X in which r = 1 and GpR is a radical of Formula VII, or a radical -NR'R", R' and R" identical or different being chosen from the group consisting of H, linear or branched or cyclic alkyls in C2 to C10, benzyl and said R' and R" alkyls which together may form one or more saturated, unsaturated and / or aromatic carbon rings and / or may include heteroatoms, chosen from the group consisting of O, N and S, at least one of the Ri or R2 is a hydrophobic radical as defined above, X represents an H or a cationic entity chosen from the group comprising metallic cations; n + m represents the degree of polymerization DP of the co-polyamino acid, that is, the average number of monomeric units per co-polyamino acid chain, and 5 < n + m < 250. [000225] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXX, XXXa, XXXa', XXXb, XXXb' or XXXb" in which the group D is a -CH2- group (aspartic unit). [000226] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formula XXX, XXXa, XXXa', XXXb, XXXb' or XXXb" in which the group D is a -CH2-CH2- group (glutamic unit). [000227] In one embodiment, the composition according to the invention is characterized in that Ri is a radical selected from the group consisting of a linear acyl group at C2 to C10, a branched acyl group at C4 to C10, a benzyl, a terminal "amino acid" unit and a pyroglutamate. [000228] In one embodiment, the composition according to the invention is characterized in that Ri is a radical chosen from the group consisting of a linear acyl group in C2 to C10 or a branched acyl group in C4 to C10. [000229] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is chosen from the co-polyamino acids of formulas XXXa, XXXb, XXXb' or XXXb" in which the co-polyamino acid is chosen from the co-polyamino acids in which the group D is a -CH2- group (aspartic unit). [000230] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from the co-polyamino acids of formulas XXXa, XXXb, XXXb' or XXXb' in which the co-polyamino acid is selected from the co- polyamino acids in which the D group is a -CH2-CH2- group (glutamic unit). [000231] In one embodiment, the composition according to the invention is characterized in that n + m is between 10 and 200. [000232] In one embodiment, the composition according to the invention is characterized in that n + m is between 15 and 150. [000233] In one embodiment, the composition according to the invention is characterized in that n + m is between 15 and 100. [000234] In one embodiment, the composition according to the invention is characterized in that n + m is between 15 and 80. [000235] In one embodiment, the composition according to the invention is characterized in that n + m is between 15 and 65. [000236] In one embodiment, the composition according to the invention is characterized in that n + m is between 20 and 60. [000237] In one embodiment, the composition according to the invention is characterized in that n + m is between 20 and 50. [000238] In one embodiment, the composition according to the invention is characterized in that n + m is between 20 and 40. [000239] The invention also relates to the co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy, said co-polyamino acid being composed of glutamic or aspartic units and said hydrophobic radicals Hy chosen from the radicals of formula X as defined below: Formula X in which GpR is chosen from among the radicals of formulas VII, VU' or VU": ; GpG and GpH, identical or different, are chosen from the radicals of formulas XI or XI': NH-G-NH- * Formula XI Formula XI' GpA is chosen from among the radicals of formula VIII Formula VIII In which A' is chosen from among the radicals of formula VIII', VIII" or VIII' Formula VIII' Formula VIII' Formula VIII' -GpL is chosen from among the radicals of formula XII Formula XII, GpC is a radical with formula IX: Formula IX; the * indicate the attachment sites of the different groups linked by amide functions; a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 1, 2 or 3 if a = 1; a' is an integer equal to 1, 2 or 3; b is an integer equal to 0 or 1; c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; d is an integer equal to 0, 1 or 2; e is an integer equal to 0 or 1; g is an integer equal to 0, 1, 2, 3, 4, 5 or 6; h is an integer equal to 0, 1, 2, 3, 4, 5 or 6, and at least one of g, h or I is different from 0; I is an integer equal to 0 or 1 and = 1 if I = 0 and = 2 if I = 1; r is an integer equal to 0, 1, or 2, and s' is an integer equal to 0 or 1; and if e is different from 0 then at least one of the g, h or I is different from 0; and if a = 0 then 1 = 0; A, Ai, Ai and A3, identical or different, are linear or branched alkyl radicals comprising from 1 to 8 carbon atoms, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring; B is an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms, or a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising 1 to 9 carbon atoms. C x is a linear or branched monovalent alkyl radical possibly including a cyclic portion, in which x indicates the number of carbon atoms and: ■ When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x < 25, ■ When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, ■ When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, ■ When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, • When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, G is a linear or branched divalent alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid functions, R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched, comprising 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched, comprising 1 to 12 carbon atoms bearing one or more -CONH2 functions or an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms, The hydrophobic radical(s) -Hy of formula X being linked to PLG: via a covalent bond between a carbonyl group of the hydrophobic radical -Hy and a nitrogen atom on the PLG, thus forming an amide function resulting from the reaction of an amine group on the PLG and an acid group on the precursor -Hy' of the hydrophobic radical -Hy, and via a covalent bond between a nitrogen atom of the hydrophobic radical -Hy and a carbonyl group carried by the PLG thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical -Hy and an acid function carried by the PLG, the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between 0 < M < 0.5; When several hydrophobic radicals are carried by a co-polyamino acid, they are either identical or different. the degree of DP polymerization in glutamic or aspartic units for PLG chains is between 5 and 250; - the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K + . [000240] The invention also relates to the precursor Hy' of the hydrophobic radical -Hy of formula X' as defined below: Formula X' in which GpR is chosen from among the radicals of formulas VII, VU' or VU": GpG and GpH, identical or different, are chosen from the radicals of formulas XI or XI': * - NH - G - NH - * Formula XI Formula XI' GpA is chosen from among the radicals of formula VIII Formula VIII In which A' is chosen from among the radicals of formula VIII', VIII" or VIII' Formula VIII' Formula VIII" Formula VIII' -GpL is chosen from among the radicals of formula XII Formula XII, GpC is a radical with formula IX: Formula IX; the * indicate the attachment sites of the different groups linked by amide functions; a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 1, 2 or 3 if a = 1; a' is an integer equal to 1, 2 or 3; b is an integer equal to 0 or 1; c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; d is an integer equal to 0, 1 or 2; e is an integer equal to 0 or 1; g is an integer equal to 0, 1, 2, 3, 4, 5 or 6; h is an integer equal to 0, 1, 2, 3, 4, 5 or 6, and at least one of g, h or I is different from 0; I is an integer equal to 0 or 1 and = 1 if I = 0 and = 2 if I = 1; r is an integer equal to 0, 1, or 2, and s' is an integer equal to 0 or 1; and if e is different from 0 then at least one of the g, h or I is different from 0; and if a = 0 then 1 = 0; A, Ai, Ai and A3, identical or different, are linear or branched alkyl radicals comprising from 1 to 8 carbon atoms, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring; B is an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms, or a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising 1 to 9 carbon atoms. C x is a linear or branched monovalent alkyl radical possibly including a cyclic portion, in which x indicates the number of carbon atoms and: ■ When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x < 25, ■ When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, « When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, ■ When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, "When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, G is a linear or branched divalent alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid functions, R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched, comprising 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched, comprising 1 to 12 carbon atoms bearing one or more -CONH2 functions or an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms, The hydrophobic radical(s) -Hy of formula X being linked to PLG: via a covalent bond between a carbonyl group of the hydrophobic radical -Hy and a nitrogen atom on the PLG, thus forming an amide function resulting from the reaction of an amine group on the PLG and an acid group on the precursor -Hy' of the hydrophobic radical -Hy, and via a covalent bond between a nitrogen atom of the hydrophobic radical -Hy and a carbonyl group carried by the PLG thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical -Hy and an acid function carried by the PLG, the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between 0 < M < 0.5; When several hydrophobic radicals are carried by a co-polyamino acid, they are either identical or different. the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K+ . [000241] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by polymerization. [000242] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by ring-opening polymerization of a glutamic acid N-carboxyanhydride derivative or an aspartic acid N-carboxyanhydride derivative. [000243] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by polymerization of a glutamic acid N-carboxyanhydride derivative or an aspartic acid N-carboxyanhydride derivative as described in the journal article Adv. Polym. Sci. 2006, 202, 1-18 (Deming, TJ). [000244] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by polymerization of a glutamic acid N-carboxyanhydride derivative. [000245] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by polymerization of a glutamic acid N-carboxyanhydride derivative selected from the group consisting of methyl polyglutamate N-carboxyanhydride (GluOMe-NCA), benzyl polyglutamate N-carboxyanhydride (GluOBzl-NCA) and t-butyl polyglutamate N-carboxyanhydride (GluOtBu-NCA). [000246] In one embodiment, the glutamic acid N-carboxyanhydride derivative is methyl poly-L-glutamate N-carboxyanhydride (L-GluOMe-NCA). [000247] In one embodiment, the glutamic acid N-carboxyanhydride derivative is benzyl poly-L-glutamate N-carboxyanhydride (L-GluOBzl-NCA). [000248] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by polymerization of a glutamic acid N-carboxyanhydride derivative or an aspartic acid N-carboxyanhydride derivative using as an initiator an organometallic complex of a transition metal as described in the publication Nature 1997, 390, 386-389 (Deming, TJ.). [000249] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by polymerization of a derivative of glutamic acid N-carboxyanhydride or of a derivative of aspartic acid N-carboxyanhydride using ammonia or a primary amine as an initiator as described in patent FR 2,801,226 (Touraud, F.; et al.) and the references cited by that patent. [000250] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by polymerization of a glutamic acid N-carboxyanhydride derivative or an aspartic acid N-carboxyanhydride derivative using as an initiator hexamethyldisilazane as described in the publication J. Am. Chem. Soc. 2007, 129, 14114-14115 (Lu H.; et al.) or a silylated amine as described in the publication J. Am. Chem. Soc. 2008, 130, 12562-12563 (Lu H.; et al.). [000251] In one embodiment, the composition according to the invention is characterized in that the process for synthesizing the polyamino acid obtained by polymerization of a derivative of glutamic acid N-carboxyanhydride or of a derivative of aspartic acid N-carboxyanhydride from which the co-polyamino acid is derived comprises a step of hydrolysis of ester functions. [000252] In one embodiment, this ester function hydrolysis step may consist of hydrolysis in acidic medium or hydrolysis in basic medium or be carried out by hydrogenation. [000253] In one embodiment, this step of hydrolysis of ester groups is an acid hydrolysis. [000254] In one embodiment, this step of hydrolysis of ester groups is carried out by hydrogenation. [000255] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by depolymerization of a higher molecular weight polyamino acid. [000256] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by enzymatic depolymerization of a higher molecular weight polyamino acid. [000257] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by chemical depolymerization of a higher molecular weight polyamino acid. [000258] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by enzymatic and chemical depolymerization of a higher molecular weight polyamino acid. [000259] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by depolymerization of a higher molecular weight polyamino acid chosen from the group consisting of sodium polyglutamate and sodium polyaspartate. [000260] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by depolymerization of a higher molecular weight sodium polyglutamate. [000261] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is derived from a polyamino acid obtained by depolymerization of a higher molecular weight sodium polyaspartate. [000262] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is obtained by grafting a hydrophobic group onto an acidic poly-L-glutamic acid or acidic poly-L-aspartic acid using the amide bond formation processes well known to those skilled in the art. [000263] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is obtained by grafting a hydrophobic group onto an acidic poly-L-glutamic acid or acidic poly-L-aspartic acid using the amide bond formation processes used for peptide synthesis. [000264] In one embodiment, the composition according to the invention is characterized in that the co-polyamino acid is obtained by grafting a hydrophobic group onto a poly-L-glutamic acid or poly-L-aspartic acid as described in patent FR 2,840,614 (Chan, YP; et al.). [000265] In the following, the units used for insulins are those recommended by the pharmacopoeias, the corresponding values ​​in mg / ml of which are given in the table below: [000266] Basal insulin with an isoelectric point between 5.8 and 8.5 is understood to be an insoluble insulin at pH 7 and with a duration of action between 8 and 24 hours or longer in standard models of diabetes. [000267] These basal insulins, whose isoelectric point is between 5.8 and 8.5, are recombinant insulins whose primary structure has been modified mainly by the introduction of basic amino acids such as Arginine or Lysine. They are described, for example, in the following patents, patent applications, or publications: WO 2003 / 053339, WO 2004 / 096854, US 5,656,722, and US 6,100,376, the contents of which are incorporated by reference. [000268] In one embodiment, the basal insulin with an isoelectric point between 5.8 and 8.5 is insulin glargine. Insulin glargine is marketed under the brand name Lantus. ® (100 U / ml) or Toujeo ® (300 U / ml) by SANOFI. [000269] In one embodiment, the basal insulin whose isoelectric point is between 5.8 and 8.5 is a biosimilar insulin glargine. [000270] A biosimilar insulin glargine is being marketed under the brand name Abasaglar® or Basaglar ® by ELI LILLY. [000271] In one embodiment, the compositions according to the invention comprise between 40 and 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000272] In one embodiment, the compositions according to the invention comprise 40 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000273] In one embodiment, the compositions according to the invention comprise 75 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000274] In one embodiment, the compositions according to the invention comprise 100 U / mL (i.e. about 3.6 mg / mL) of basal insulin having an isoelectric point between 5.8 and 8.5. [000275] In one embodiment, the compositions according to the invention comprise 150 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000276] In one embodiment, the compositions according to the invention comprise 200 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000277] In one embodiment, the compositions according to the invention include 225 U / mL of basal insulin with an isoelectric point between 5.8 and 8.5. [000278] In one embodiment, the compositions according to the invention comprise 250 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000279] In one embodiment, the compositions according to the invention comprise 300 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000280] In one embodiment, the compositions according to the invention comprise 400 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000281] In one embodiment, the compositions according to the invention comprise 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5. [000282] In one embodiment, the mass ratio between basal insulin, whose isoelectric point is between 5.8 and 8.5, and co-polyamino acid, i.e. co-polyamino acid / basal insulin, is between 0.2 and 8. [000283] In one embodiment, the mass ratio is between 0.2 and 6. [000284] In one embodiment, the mass ratio is between 0.2 and 5. [000285] In one embodiment, the mass ratio is between 0.2 and 4. [000286] In one embodiment, the mass ratio is between 0.2 and 3. [000287] In one embodiment, the mass ratio is between 0.2 and 2. [000288] In one embodiment, the mass ratio is between 0.2 and 1. [000289] In one embodiment, the concentration of co-polyamino acid carrying carboxylate charges and hydrophobic radicals is at most 60 mg / mL. [000290] In one embodiment, the concentration of co-polyamino acid carrying carboxylate charges and hydrophobic radicals is at most 40 mg / mL. [000291] In one embodiment, the concentration of co-polyamino acid carrying carboxylate charges and hydrophobic radicals is at most 20 mg / mL. [000292] In one embodiment, the concentration of co-polyamino acid carrying carboxylate charges and hydrophobic radicals is at most 10 mg / mL. [000293] In one embodiment, the concentration of co-polyamino acid carrying carboxylate charges and hydrophobic radicals is at most 5 mg / ml. [000294] In one embodiment, the concentration of the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is at most 2.5 mg / ml. [000295] In one embodiment, the compositions according to the invention further comprise prandial insulin. Prandial insulins are soluble at pH 7. [000296] Prandial insulin is understood to mean rapid or "regular" insulin. [000297] Rapid prandial insulins are insulins that must meet the needs caused by the ingestion of proteins and carbohydrates during a meal; they must act in less than 30 minutes. [000298] In one embodiment, prandial insulin referred to as "regular" is human insulin. [000299] In one embodiment, prandial insulin is recombinant human insulin as described in the European Pharmacopoeia and the American Pharmacopoeia. [000300] Human insulin is marketed, for example, under the brand name Humulin ® (ELI LILLY) and Novolin ® (NOVO NORDISK). [000301] So-called very rapid (fast acting) prandial insulins are insulins which are obtained by recombination and whose primary structure has been modified to decrease their time of action. [000302] In one embodiment, so-called very rapid-acting prandial insulins are chosen from the group including insulin lispro (Humalog ® ), insulin glulisine (Apidra®) and insulin aspart (NovoLog ® ). [000303] In one embodiment, prandial insulin is lispro insulin. [000304] In one embodiment, prandial insulin is insulin glulisine. [000305] In one embodiment, prandial insulin is insulin aspart. [000306] In one embodiment, the compositions according to the invention comprise in total between 60 and 800 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000307] In one embodiment, the compositions according to the invention comprise in total between 100 and 500 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000308] In one embodiment, the compositions according to the invention comprise a total of 800 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000309] In one embodiment, the compositions according to the invention comprise a total of 700 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000310] In one embodiment, the compositions according to the invention comprise a total of 600 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000311] In one embodiment, the compositions according to the invention comprise a total of 500 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000312] In one embodiment, the compositions according to the invention comprise a total of 400 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000313] In one embodiment, the compositions according to the invention comprise a total of 300 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000314] In one embodiment, the compositions according to the invention comprise a total of 266 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000315] In one embodiment, the compositions according to the invention comprise a total of 200 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000316] In one embodiment, the compositions according to the invention comprise a total of 100 U / mL of insulin with a combination of prandial and basal insulin whose isoelectric point is between 5.8 and 8.5. [000317] The proportions between basal insulin, whose isoelectric point is between 5.8 and 8.5, and prandial insulin are, for example, expressed as percentages of 25 / 75, 30 / 70, 40 / 60, 50 / 50, 60 / 40, 63 / 37, 70 / 30, 75 / 25, 80 / 20, 83 / 17, 90 / 10 for formulations such as those described above containing 60 to 800 U / mL. However, any other proportion may be achieved. [000318] In one embodiment, basal insulin with an isoelectric point between 5.8 and 8.5 and prandial insulin are present respectively in the following concentrations (in U / ml) 75 / 25, 150 / 50, 200 / 66 or 300 / 100. [000319] In one embodiment, basal insulin, whose isoelectric point is between 5.8 and 8.5, and prandial insulin are present respectively in the following concentrations (in U / ml): 75 / 25. [000320] In one embodiment, basal insulin, whose isoelectric point is between 5.8 and 8.5, and prandial insulin are present respectively in the following concentrations (in U / ml) 150 / 50. [000321] The hydrophobic radical ratio per basal insulin is defined as the ratio of their respective molar concentrations: [Hy] / [basal insulin] (mol / mol) to obtain the expected performance, namely the solubilization of basal insulin at pH between 6.0 and 8.0, the precipitation of basal insulin and the stability of the compositions according to the invention. [000322] The minimum value of the hydrophobic radical per basal insulin [Hy] / [basal insulin] ratio, measured, is the value at which the basal insulin is solubilized, since solubilization is the minimum effect to be obtained; this solubilization conditions all the other technical effects which can only be observed if basal insulin is solubilized at pH between 6.0 and 8.0. [000323] In the compositions according to the invention, the hydrophobic radical ratio per basal insulin [Hy] / [basal insulin] may be greater than the minimum value determined by the solubilization limit. [000324] In one embodiment, the hydrophobic radical ratio per basal insulin [Hy] / [basal insulin] <3. [000325] In one embodiment, the ratio of hydrophobic radical to basal insulin [Hy] / [basal insulin] <2. [000326] In one embodiment, the ratio of hydrophobic radical to basal insulin [Hy] / [basal insulin] < 1.75. [000327] In one embodiment, the hydrophobic radical ratio per basal insulin [Hy] / [basal insulin] < 1.5. [000328] In one embodiment, the hydrophobic radical ratio per basal insulin [Hy] / [basal insulin] < 1.25. [000329] In one embodiment, the hydrophobic radical ratio per basal insulin [Hy] / [basal insulin] < 1.00. [000330] In one embodiment, the hydrophobic radical ratio per basal insulin [Hy] / [basal insulin] < 0.75. [000331] In one embodiment, the ratio of hydrophobic radical to basal insulin [Hy] / [basal insulin] < 0.5. [000332] In one embodiment, the hydrophobic radical ratio per basal insulin [Hy] / [basal insulin] < 0.25. [000333] In one embodiment, the compositions according to the invention further comprise a gastrointestinal hormone. [000334] The term “gastrointestinal hormones” means hormones selected from the group consisting of GLP-1 RA (Glucagon like peptide-1 receptor agonist) and GIP (Glucose-dependent insulinotropic peptide), oxyntomodulin (a proglucagon derivative), peptide YY, amylin, cholecystokinin, pancreatic polypeptide (PP), ghrelin and enterostatin, their analogues or derivatives and / or their pharmaceutically acceptable salts. [000335] In one embodiment, the gastrointestinal hormones are GLP-1 RA analogues or derivatives selected from the group consisting of exenatide or Byetta ® (ASTRA-ZENECA), liraglutide or Victoza ® (NOVO NORDISK), lixisenatide or Lyxumia® (SANOFI), albiglutide or Tanzeum ® (GSK) or dulaglutide or Trulicity ® (ELI LILLY & CO), their analogues or derivatives and their pharmaceutically acceptable salts. [000336] In one embodiment, the gastrointestinal hormone is pramlintide or Symlin ® ® (ASTRA-ZENECA). [000337] In one embodiment, the gastrointestinal hormone is exenatide or Byetta ® , its analogues or derivatives and their pharmaceutically acceptable salts. [000338] In one embodiment, the gastrointestinal hormone is liraglutide or Victoza ® , its analogues or derivatives and their pharmaceutically acceptable salts. [000339] In one embodiment, the gastrointestinal hormone is lixisenatide or Lyxumia ® , its analogues or derivatives and their pharmaceutically acceptable salts. [000340] In one embodiment, the gastrointestinal hormone is albiglutide or Tanzeum ® , its analogues or derivatives and their pharmaceutically acceptable salts. [000341] In one embodiment, the gastrointestinal hormone is dulaglutide or Trulicity®, its analogues or derivatives and their pharmaceutically acceptable salts. [000342] In one embodiment, the gastrointestinal hormone is pramlintide or Symlin®, its analogues or derivatives and their pharmaceutically acceptable salts. [000343] When used by reference to a peptide or protein, the term "analog" means a peptide or protein in which one or more constituent amino acid residues have been substituted by other amino acid residues and / or in which one or more constituent amino acid residues have been deleted and / or in which one or more constituent amino acid residues have been added. The percentage of homology permitted for the present definition of an analog is 50%. [000344] The term "derivative", when used by reference to a peptide or protein, means a peptide or protein or analogue chemically modified by a substituent not present in the reference peptide or protein or analogue, i.e. a peptide or protein that has been modified by the creation of covalent bonds to introduce substituents. [000345] In one embodiment, the substituent is chosen from the group consisting of fatty chains. [000346] In one embodiment, the concentration of gastrointestinal hormone is within a range of 0.01 to 100 mg / mL. [000347] In one embodiment, the concentration of exenatide, its analogues or derivatives and their pharmaceutically acceptable salts is within a range of 0.04 to 0.5 mg / mL. [000348] In one embodiment, the concentration of liraglutide, its analogues or derivatives and their pharmaceutically acceptable salts is within a range of 1 to 10 mg / mL. [000349] In one embodiment, the concentration of lixisenatide, its analogues or derivatives and their pharmaceutically acceptable salts is within a range of 0.01 to 1 mg / mL. [000350] In one embodiment, the concentration of albiglutide, its analogues or derivatives and their pharmaceutically acceptable salts is between 5 and 100 mg / mL. [000351] In one embodiment, the concentration of dulaglutide, its analogues or derivatives and their pharmaceutically acceptable salts is between 0.1 and 10 mg / mL. [000352] In one embodiment, the concentration of pramlintide, its analogues or derivatives and their pharmaceutically acceptable salts is between 0.1 and 5 mg / mL. [000353] In one embodiment, the compositions according to the invention are made by mixing commercial solutions of basal insulin having an isoelectric point between 5.8 and 8.5 and commercial solutions of GLP-1 RA, analogue or derivative of GLP-1 RA in volume ratios within a range of 10 / 90 to 90 / 10. [000354] In one embodiment, the composition according to the invention comprises a daily dose of basal insulin and a daily dose of gastrointestinal hormone. [000355] In one embodiment, the compositions according to the invention comprise between 40 U / mL and 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and between 0.05 and 0.5 mg / mL of exenatide. [000356] In one embodiment, the compositions according to the invention comprise between 40 U / mL and 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and, from 1 to 10 mg / mL of liraglutide. [000357] In one embodiment, the compositions according to the invention comprise between 40 U / mL and 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and, from 0.01 to 1 mg / mL of lixisenatide. [000358] In one embodiment, the compositions according to the invention comprise between 40 U / mL and 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and, from 5 to 100 mg / mL of albiglutide. [000359] In one embodiment, the compositions according to the invention comprise between 40 U / mL and 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and, from 0.1 to 10 mg / mL of dulaglutide. [000360] In one embodiment, the compositions according to the invention comprise 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.04 to 0.5 mg / mL of exenatide. [000361] In one embodiment, the compositions according to the invention comprise 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 1 to 10 mg / mL of liraglutide. [000362] In one embodiment, the compositions according to the invention comprise 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.01 to 1 mg / mL of lixisenatide. [000363] In one embodiment, the compositions according to the invention comprise 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 5 to 100 mg / mL of albiglutide. [000364] In one embodiment, the compositions according to the invention include 500 U / mL of basal insulin with an isoelectric point between 5.8 and 8.5 and 0.1 to 10 mg / mL of dulaglutide. [000365] In one embodiment, the compositions according to the invention comprise 400 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.04 to 0.5 mg / mL of exenatide. [000366] In one embodiment, the compositions according to the invention comprise 400 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 1 to 10 mg / mL of liraglutide. [000367] In one embodiment, the compositions according to the invention comprise 400 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.01 to 1 mg / mL of lixisenatide. [000368] In one embodiment, the compositions according to the invention comprise 400 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 5 to 100 mg / mL of albiglutide. [000369] In one embodiment, the compositions according to the invention comprise 400 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.1 to 10 mg / mL of dulaglutide. [000370] In one embodiment, the compositions according to the invention include 300 U / mL of basal insulin with an isoelectric point between 5.8 and 8.5 and 0.04 to 0.5 mg / mL of exenatide. [000371] In one embodiment, the compositions according to the invention comprise 300 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 1 to 10 mg / mL of liraglutide. [000372] In one embodiment, the compositions according to the invention comprise 300 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.01 to 1 mg / mL of lixisenatide. [000373] In one embodiment, the compositions according to the invention comprise 300 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 5 to 100 mg / mL of albiglutide. [000374] In one embodiment, the compositions according to the invention comprise 300 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.1 to 10 mg / mL of dulaglutide. [000375] In one embodiment, the compositions according to the invention comprise 225 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.04 to 0.5 mg / mL of exenatide. [000376] In one embodiment, the compositions according to the invention comprise 225 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 1 to 10 mg / mL of liraglutide. [000377] In one embodiment, the compositions according to the invention comprise 225 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.01 to 1 mg / mL of lixisenatide. [000378] In one embodiment, the compositions according to the invention comprise 225 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 5 to 100 mg / mL of albiglutide. [000379] In one embodiment, the compositions according to the invention comprise 225 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and, from 0.1 to 10 mg / mL of dulaglutide. [000380] In one embodiment, the compositions according to the invention comprise 200 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.04 to 0.5 mg / mL of exenatide. [000381] In one embodiment, the compositions according to the invention include 200 U / mL of basal insulin with an isoelectric point between 5.8 and 8.5 and 1 to 10 mg / mL of liraglutide. [000382] In one embodiment, the compositions according to the invention comprise 200 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.01 to 1 mg / mL of lixisenatide. [000383] In one embodiment, the compositions according to the invention comprise 200 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 5 to 100 mg / mL of albiglutide. [000384] In one embodiment, the compositions according to the invention comprise 200 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.1 to 10 mg / mL of dulaglutide. [000385] In one embodiment, the compositions according to the invention comprise 100 U / mL (i.e. about 3.6 mg / mL) of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.04 to 0.5 mg / mL of exenatide. [000386] In one embodiment, the compositions according to the invention include 100 U / mL (approximately 3.6 mg / mL) of basal insulin with an isoelectric point between 5.8 and 8.5 and 1 to 10 mg / mL of liraglutide. [000387] In one embodiment, the compositions according to the invention comprise 100 U / mL (i.e. about 3.6 mg / mL) of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.01 to 1 mg / mL of lixisenatide. [000388] In one embodiment, the compositions according to the invention comprise 100 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 5 to 100 mg / mL of albiglutide. [000389] In one embodiment, the compositions according to the invention comprise 100 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.1 to 10 mg / mL of dulaglutide. [000390] In one embodiment, the compositions according to the invention comprise 40 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.04 to 0.5 mg / mL of exenatide. [000391] In one embodiment, the compositions according to the invention comprise 40 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 1 to 10 mg / mL of liraglutide. [000392] In one embodiment, the compositions according to the invention include 40 U / mL of basal insulin with an isoelectric point between 5.8 and 8.5 and 0.01 to 1 mg / mL of lixisenatide. [000393] In one embodiment, the compositions according to the invention comprise 40 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 5 to 100 mg / mL of albiglutide. [000394] In one embodiment, the compositions according to the invention comprise 40 U / mL of basal insulin having an isoelectric point between 5.8 and 8.5 and 0.1 to 10 mg / mL of dulaglutide. [000395] The invention also relates to compositions which further comprise ionic species, said ionic species making it possible to improve the stability of the compositions. [000396] The invention also relates to the use of ionic species selected from the group of anions, cations and / or zwitterions to improve the physico-chemical stability of the compositions. [000397] In one embodiment, the ionic species comprise less than 10 carbon atoms. [000398] Said ionic species are chosen from the group of anions, cations and / or zwitterions. By zwitterion is meant a species bearing at least one positive charge and at least one negative charge on two non-adjacent atoms. [000399] Said ionic species are used alone or in mixture and preferably in mixture. [000400] In one embodiment, the anions are chosen from among the organic anions. [000401] In one embodiment, the organic anions comprise less than 10 carbon atoms. [000402] In one embodiment, the organic anions are chosen from the group consisting of acetate, citrate and succinate [000403] In one embodiment, the anions are chosen from anions of mineral origin. [000404] In one embodiment, the anions of mineral origin are chosen from the group consisting of sulfates, phosphates and halides, in particular chlorides. [000405] In one embodiment, the cations are chosen from among the organic cations. [000406] In one embodiment, the organic cations comprise less than 10 carbon atoms. [000407] In one embodiment, the organic cations are chosen from the group consisting of ammoniums, for example 2-Amino-2-(hydroxymethyl)propane-1,3-diol where the amine is in the form of ammonium. [000408] In one embodiment, the cations are chosen from among the cations of mineral origin. [000409] In one embodiment, the cations of mineral origin are chosen from the group consisting of zinc, in particular Zn2+ and the alkali metals, in particular Na+ and K+ , [000410] In one embodiment, the zwitterions are chosen from among the zwitterions of organic origin. [000411] In one embodiment, the organically sourced zwitterions are chosen from amino acids. [000412] In one embodiment, the amino acids are chosen from the aliphatic amino acids in the group consisting of glycine, alanine, vain, isoleucine and leucine. [000413] In one embodiment, the amino acids are chosen from among the cyclic amino acids in the group consisting of proline. [000414] In one embodiment, the amino acids are chosen from among the hydroxylated or sulfur-containing amino acids in the group consisting of cysteine, serine, threonine, and methionine. [000415] In one embodiment, the amino acids are chosen from the aromatic amino acids in the group consisting of phenylalanine, tyrosine and tryptophan. [000416] In one embodiment, the amino acids are chosen from among the amino acids whose carboxyl function of the side chain is amidified in the group consisting of asparagine and glutamine. [000417] In one embodiment, the zwitterions of organic origin are chosen from the group consisting of amino acids having an uncharged side chain. [000418] In one embodiment, the zwitterions of organic origin are chosen from the group consisting of aminodiacids or acidic amino acids. [000419] In one embodiment, the aminodiacids are chosen from the group consisting of glutamic acid and aspartic acid, possibly in the form of salts. [000420] In one embodiment, the zwitterions of organic origin are chosen from the group consisting of basic or so-called "cationic" amino acids. [000421] In one embodiment, the so-called "cationic" amino acids are chosen from arginine, histidine and lysine, in particular arginine and lysine. [000422] In particular, zwitterions comprise as many negative charges as positive charges and therefore an overall charge of zero at the isoelectric point and / or at a pH between 6.0 and 8.0. [000423] These ionic species are introduced into the compositions in the form of salts. The introduction of these salts may be in solid form before being dissolved in the compositions, or in the form of a solution, in particular a concentrated solution. [000424] For example, the cations of mineral origin are supplied in the form of salts chosen from sodium chloride, zinc chloride, sodium phosphate, sodium sulfate, etc. [000425] For example, anions of organic origin are supplied in the form of salts chosen from sodium or potassium citrate, sodium acetate. [000426] For example, amino acids are added in the form of salts selected from arginine hydrochloride, histidine hydrochloride or in non-salted form such as histidine, arginine. [000427] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 10 mM. [000428] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 20 mM. [000429] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 30 mM. [000430] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 50 mM. [000431] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 75 mM. [000432] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 100 mM. [000433] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 200 mM. [000434] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 300 mM. [000435] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 500 mM. [000436] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 600 mM. [000437] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 700 mM. [000438] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 800 mM. [000439] In one embodiment, the total molar concentration of ionic species in the composition is greater than or equal to 900 mM. [000440] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 1000 mM. [000441] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 1500 mM. [000442] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 1200 mM. [000443] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 1000 mM. [000444] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 900 mM. [000445] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 800 mM. [000446] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 700 mM. [000447] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 600 mM. [000448] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 500 mM. [000449] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 400 mM. [000450] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 300 mM. [000451] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 200 mM. [000452] In one embodiment, the total molar concentration of ionic species in the composition is less than or equal to 100 mM. [000453] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 1000 mM. [000454] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 1000 mM. [000455] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 1000 mM. [000456] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 1000 mM. [000457] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 1000 mM. [000458] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 1000 mM. [000459] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 1000 mM. [000460] In one embodiment, the total molar concentration of ionic species in the composition is between 300 and 1000 mM. [000461] In one embodiment, the total molar concentration of ionic species in the composition is between 400 and 1000 mM. [000462] In one embodiment, the total molar concentration of ionic species in the composition is between 500 and 1000 mM. [000463] In one embodiment, the total molar concentration of ionic species in the composition is between 600 and 1000 mM. [000464] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 900 mM. [000465] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 900 mM. [000466] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 900 mM. [000467] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 900 mM. [000468] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 900 mM. [000469] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 900 mM. [000470] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 900 mM. [000471] In one embodiment, the total molar concentration of ionic species in the composition is between 300 and 900 mM. [000472] In one embodiment, the total molar concentration of ionic species in the composition is between 400 and 900 mM. [000473] In one embodiment, the total molar concentration of ionic species in the composition is between 500 and 900 mM. [000474] In one embodiment, the total molar concentration of ionic species in the composition is between 600 and 900 mM. [000475] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 900 mM. [000476] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 800 mM. [000477] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 800 mM. [000478] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 800 mM. [000479] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 800 mM. [000480] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 800 mM. [000481] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 800 mM. [000482] In one embodiment, the total molar concentration of ionic species in the composition is between 300 and 800 mM. [000483] In one embodiment, the total molar concentration of ionic species in the composition is between 400 and 800 mM. [000484] In one embodiment, the total molar concentration of ionic species in the composition is between 500 and 800 mM. [000485] In one embodiment, the total molar concentration of ionic species in the composition is between 600 and 800 mM. [000486] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 700 mM. [000487] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 700 mM. [000488] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 700 mM. [000489] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 700 mM. [000490] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 700 mM. [000491] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 700 mM. [000492] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 700 mM. [000493] In one embodiment, the total molar concentration of ionic species in the composition is between 300 and 700 mM. [000494] In one embodiment, the total molar concentration of ionic species in the composition is between 400 and 700 mM. [000495] In one embodiment, the total molar concentration of ionic species in the composition is between 500 and 700 mM. [000496] In one embodiment, the total molar concentration of ionic species in the composition is between 600 and 700 mM. [000497] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 600 mM. [000498] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 600 mM. [000499] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 600 mM. [000500] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 600 mM. [000501] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 600 mM. [000502] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 600 mM. [000503] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 600 mM. [000504] In one embodiment, the total molar concentration of ionic species in the composition is between 300 and 600 mM. [000505] In one embodiment, the total molar concentration of ionic species in the composition is between 400 and 600 mM. [000506] In one embodiment, the total molar concentration of ionic species in the composition is between 500 and 600 mM. [000507] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 500 mM. [000508] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 500 mM. [000509] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 500 mM. [000510] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 500 mM. [000511] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 500 mM. [000512] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 500 mM. [000513] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 500 mM. [000514] In one embodiment, the total molar concentration of ionic species in the composition is between 300 and 500 mM. [000515] In one embodiment, the total molar concentration of ionic species in the composition is between 400 and 500 mM. [000516] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 400 mM. [000517] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 400 mM. [000518] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 400 mM. [000519] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 400 mM. [000520] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 400 mM. [000521] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 400 mM. [000522] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 400 mM. [000523] In one embodiment, the total molar concentration of ionic species in the composition is between 300 and 400 mM. [000524] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 300 mM. [000525] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 300 mM. [000526] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 300 mM. [000527] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 300 mM. [000528] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 300 mM. [000529] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 300 mM. [000530] In one embodiment, the total molar concentration of ionic species in the composition is between 200 and 300 mM. [000531] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 200 mM. [000532] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 200 mM. [000533] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 200 mM. [000534] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 200 mM. [000535] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 200 mM. [000536] In one embodiment, the total molar concentration of ionic species in the composition is between 100 and 200 mM. [000537] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 100 m M. [000538] In one embodiment, the total molar concentration of ionic species in (a composition is between 20 and 100 mM. [000539] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 100 mM. [000540] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 100 mM. [000541] In one embodiment, the total molar concentration of ionic species in the composition is between 75 and 100 mM. [000542] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 75 mM. [000543] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 75 mM. [000544] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 75 mM. [000545] In one embodiment, the total molar concentration of ionic species in the composition is between 50 and 75 mM. [000546] In one embodiment, the total molar concentration of ionic species in the composition is between 10 and 50 mM. [000547] In one embodiment, the total molar concentration of ionic species in the composition is between 20 and 50 mM. [000548] In one embodiment, the total molar concentration of ionic species in the composition is between 30 and 50 mM. [000549] In one embodiment, said ionic species are present in a concentration ranging from 5 to 400 mM. [000550] In one embodiment, said ionic species are present in a concentration ranging from 5 to 300 mM. [000551] In one embodiment, said ionic species are present in a concentration ranging from 5 to 200 mM. [000552] In one embodiment, said ionic species are present in a concentration ranging from 5 to 100 mM. [000553] In one embodiment, said ionic species are present in a concentration ranging from 5 to 75 mM. [000554] In one embodiment, said ionic species are present in a concentration ranging from 5 to 50 mM. [000555] In one embodiment, said ionic species are present in a concentration ranging from 5 to 25 mM. [000556] In one embodiment, said ionic species are present in a concentration ranging from 5 to 20 mM. [000557] In one embodiment, said ionic species are present in a concentration ranging from 5 to 10 mM. [000558] In one embodiment, said ionic species are present in a concentration ranging from 10 to 400 mM. [000559] In one embodiment, said ionic species are present in a concentration ranging from 10 to 300 mM. [000560] In one embodiment, said ionic species are present in a concentration ranging from 10 to 200 mM. [000561] In one embodiment, said ionic species are present in a concentration ranging from 10 to 100 mM. [000562] In one embodiment, said ionic species are present in a concentration ranging from 10 to 75 mM. [000563] In one embodiment, said ionic species are present in a concentration ranging from 10 to 50 mM. [000564] In one embodiment, said ionic species are present in a concentration ranging from 10 to 25 mM. [000565] In one embodiment, said ionic species are present in a concentration ranging from 10 to 20 mM. [000566] In one embodiment, said ionic species are present in a concentration ranging from 20 to 300 mM. [000567] In one embodiment, said ionic species are present in a concentration ranging from 20 to 200 mM. [000568] In one embodiment, said ionic species are present in a concentration ranging from 20 to 100 mM. [000569] In one embodiment, said ionic species are present in a concentration ranging from 20 to 75 mM. [000570] In one embodiment, said ionic species are present in a concentration ranging from 20 to 50 mM. [000571] In one embodiment, said ionic species are present in a concentration ranging from 20 to 25 mM. [000572] In one embodiment, said ionic species are present in a concentration ranging from 50 to 300 mM. [000573] In one embodiment, said ionic species are present in a concentration ranging from 50 to 200 mM. [000574] In one embodiment, said ionic species are present in a concentration ranging from 50 to 100 mM. [000575] In one embodiment, said ionic species are present in a concentration ranging from 50 to 75 mM. [000576] With regard to cations of mineral origin and in particular Zn 2+ , its molar concentration within the composition can be between 0.25 and 20 mM, in particular between 0.25 and 10 mM or between 0.25 and 5 mM. [000577] In one embodiment, the composition includes zinc. [000578] In one embodiment, the composition comprises from 0.2 to 2 mM of zinc. [000579] In one embodiment, the composition includes IMaCI. [000580] In one embodiment, IMaCl is present in a concentration ranging from 2 to 25 mM. [000581] In one embodiment, NaCl is present in a concentration ranging from 2.5 to 20 mM. [000582] In one embodiment, NaCl is present in a concentration ranging from 4 to 15 mM. [000583] In one embodiment, NaCl is present in a concentration ranging from 5 to 10 mM. [000584] In one embodiment, the compositions according to the invention further comprise buffers. [000585] In one embodiment, the compositions according to the invention comprise buffers at concentrations between 0 and 100 mM. [000586] In one embodiment, the compositions according to the invention comprise buffers at concentrations between 15 and 50 mM. [000587] In one embodiment, the compositions according to the invention comprise a buffer selected from the group consisting of a phosphate buffer, Tris (trishydroxymethylaminomethane) and sodium citrate. [000588] In one embodiment, the buffer is sodium phosphate. [000589] In one embodiment, the buffer is the Tris (trishydroxymethylaminomethane). [000590] In one embodiment, the buffer is sodium citrate. [000591] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 0 and 5000 pM. [000592] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 0 and 4000 mM. [000593] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 0 and 3000 pM. [000594] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 0 and 2000 pM. [000595] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 0 and 1000 pM. [000596] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 50 and 600 pM. [000597] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 100 and 500 pM. [000598] In one embodiment, the compositions according to the invention further comprise zinc salts at a concentration between 200 and 500 pM. [000599] In one embodiment, the compositions according to the invention further comprise preservatives. [000600] In one embodiment, the preservatives are chosen from the group consisting of m-cresol and phenol, alone or in mixture. [000601] In one embodiment, the concentration of the preservatives is between 10 and 50 mM. [000602] In one embodiment, the concentration of the preservatives is between 10 and 40 mM. [000603] In one embodiment, the compositions according to the invention further comprise a surfactant. [000604] In one embodiment, the surfactant is chosen from the group consisting of propylene glycol and polysorbate. [000605] The compositions according to the invention may further include additives such as tonicity agents. [000606] In one embodiment, the tonicity agents are chosen from the group consisting of glycerin, sodium chloride, mannitol and glycine. [000607] The compositions according to the invention may further include all excipients conforming to pharmacopoeias and compatible with insulins used at the concentrations of use. [000608] The invention also relates to a pharmaceutical formulation according to the invention, characterized in that it is obtained by drying and / or lyophilization. [000609] In the case of local and systemic releases, the envisaged modes of administration are intravenous, subcutaneous, intradermal or intramuscular. [000610] Transdermal, oral, nasal, vaginal, ocular, buccal, and pulmonary routes of administration are also considered. [000611] In one embodiment, the composition according to the invention is characterized in that it is administered once a day. [000612] In one embodiment, the composition according to the invention is characterized in that it is administered at least twice a day. [000613] In one embodiment, the composition according to the invention is characterized in that it is administered twice a day. [000614] In one embodiment, the composition according to the invention is characterized in that it further comprises a prandial insulin. [000615] In one embodiment, the composition according to the invention further comprising at least one prandial insulin is characterized in that it is administered once a day. [000616] In one embodiment, the composition according to the invention further comprising at least one prandial insulin is characterized in that it is administered at least twice a day. [000617] In one embodiment, the composition according to the invention further comprising at least one prandial insulin is characterized in that it is administered twice a day. [000618] In one embodiment, the composition according to the invention is characterized in that it further comprises a gastrointestinal hormone. [000619] In one embodiment, the composition according to the invention further comprising at least one gastrointestinal hormone is characterized in that it is administered once a day. [000620] In one embodiment, the composition according to the invention further comprising at least one gastrointestinal hormone is characterized in that it is administered at least twice a day. [000621] In one embodiment, the composition according to the invention further comprising at least one gastrointestinal hormone is characterized in that it is administered twice a day. [000622] In one embodiment, the composition according to the invention is characterized in that the gastrointestinal hormone is a GLP-1 RA. [000623] In one embodiment, the composition according to the invention further comprising a GLP-1 RA is characterized in that it is administered once a day. [000624] In one embodiment, the composition according to the invention further comprising at least one GLP-1 RA is characterized in that it is administered at least twice a day. [000625] In one embodiment, the composition according to the invention further comprising at least one GLP-1 RA is characterized in that it is administered twice a day. [000626] The invention also relates to unit-dose formulations with a pH between 6.0 and 8.0 comprising a basal insulin whose isoelectric point is between 5.8 and 8.5. [000627] The invention also relates to unit-dose formulations with a pH between 6.0 and 8.0 comprising a basal insulin with an isoelectric point between 5.8 and 8.5 and a prandial insulin. [000628] The invention also relates to unit-dose formulations with a pH between 6.0 and 8.0 comprising a basal insulin with an isoelectric point between 5.8 and 8.5 and a gastrointestinal hormone, as defined above. [000629] The invention also relates to unit-dose formulations with a pH between 6.0 and 8.0 comprising a basal insulin with an isoelectric point between 5.8 and 8.5, a prandial insulin and a gastrointestinal hormone, as defined above. [000630] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.8 comprising a basal insulin whose isoelectric point is between 5.8 and 8.5. [000631] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.8 comprising a basal insulin with an isoelectric point between 5.8 and 8.5 and a prandial insulin. [000632] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.8 comprising a basal insulin with an isoelectric point between 5.8 and 8.5 and a gastrointestinal hormone, as defined above. [000633] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.8 comprising a basal insulin with an isoelectric point between 5.8 and 8.5, a prandial insulin and a gastrointestinal hormone, as defined above. [000634] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.6 comprising a basal insulin whose isoelectric point is between 5.8 and 8.5. [000635] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.6 comprising a basal insulin with an isoelectric point between 5.8 and 8.5 and a prandial insulin. [000636] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.6 comprising a basal insulin with an isoelectric point between 5.8 and 8.5 and a gastrointestinal hormone, as defined above. [000637] The invention also relates to unit-dose formulations with a pH between 6.6 and 7.6 comprising a basal insulin with an isoelectric point between 5.8 and 8.5, a prandial insulin and a gastrointestinal hormone, as defined above. [000638] In one embodiment, the unit-dose formulations further include a co-polyamino acid as defined above. [000639] In one embodiment, the formulations are in the form of an injectable solution. [000640] In one embodiment, the basal insulin whose isoelectric point is between 5.8 and 8.5 is insulin glargine. [000641] In one embodiment, GLP-1 RA, an analogue or derivative of GLP-1 RA, is selected from the group comprising exenatide (Byetta®), liraglutide (Victoza®). ® ), lixisenatide (Lyxumia®), albiglutide (Tanzeum ® ), dulaglutide (Trulicity®) or one of their derivatives. [000642] In one embodiment, the gastrointestinal hormone is exenatide. [000643] In one embodiment, the gastrointestinal hormone is liraglutide. [000644] In one embodiment, the gastrointestinal hormone is lixisenatide. [000645] In one embodiment, the gastrointestinal hormone is biglutide. [000646] In one embodiment, the gastrointestinal hormone is dulaglutide. [000647] The solubilization at pH between 6.0 and 8.0 of basal insulins whose isoelectric point is between 5.8 and 8.5, by co-polyamino acids carrying carboxylate charges and at least one hydrophobic radical according to the invention, can be observed and controlled in a simple way, with the naked eye, by means of a change in the appearance of the solution. [000648] The solubilization at pH between 6.6 and 7.8 of basal insulins whose isoelectric point is between 5.8 and 8.5, by co-polyamino acids carrying carboxylate charges and at least one hydrophobic radical according to the invention, can be observed and controlled in a simple way, with the naked eye, thanks to a change in the appearance of the solution. [000649] Furthermore, and just as importantly, the applicant was able to verify that a basal insulin whose isoelectric point is between 5.8 and 8.5, solubilized at pH between 6.0 and 8.0 in the presence of a co-polyamino acid carrying carboxylate charges and at least one hydrophobic radical according to the invention retains its action as a long-acting insulin whether alone or in combination with a prandial insulin or a gastrointestinal hormone. [000650] The applicant was also able to verify that prandial insulin mixed at pH between 6.0 and 8.0 in the presence of a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical according to the invention and a basal insulin, whose isoelectric point is between 5.8 and 8.5, retains its action as a rapid insulin. [000651] The preparation of a composition according to the invention has the advantage of being able to be carried out by simply mixing an aqueous solution of basal insulin with an isoelectric point between 5.8 and 8.5, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical according to the invention, in aqueous solution or in lyophilized form. If necessary, the pH of the preparation is adjusted to a pH between 6.0 and 8.0. [000652] The preparation of a composition according to the invention has the advantage of being able to be carried out by simply mixing an aqueous solution of basal insulin with an isoelectric point between 5.8 and 8.5, a prandial insulin solution, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical according to the invention, in aqueous solution or in lyophilized form. If necessary, the pH of the preparation is adjusted to a pH between 6.0 and 8.0. [000653] The preparation of a composition according to the invention has the advantage of being able to be carried out by simply mixing an aqueous solution of basal insulin having an isoelectric point between 5.8 and 8.5, a solution of GLP-1 RA, an analog or derivative of GLP-1 RA, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical according to the invention, in aqueous solution or in lyophilized form. If necessary, the pH of the preparation is adjusted to a pH between 6.0 and 8.0. [000654] The preparation of a composition according to the invention has the advantage of being able to be carried out by simply mixing an aqueous solution of basal insulin with an isoelectric point between 5.8 and 8.5, a prandial insulin solution, a solution of GLP-1 RA or a GLP-1 RA analog or derivative, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical according to the invention, in aqueous solution or in lyophilized form. If necessary, the pH of the preparation is adjusted to a pH between 6.0 and 8.0. [000655] In one embodiment, the mixture of basal insulin and co-polyamino acid is concentrated by ultrafiltration before mixing with prandial insulin in aqueous solution or in lyophilized form. [000656] If necessary, the composition of the mixture is adjusted with excipients such as glycerin, m-cresol, zinc chloride, and polysorbate (Tween ®) by adding concentrated solutions of these excipients to the mixture. If necessary, the pH of the preparation is adjusted to a pH between 6.0 and 8. Part A - Synthesis of hydrophobic intermediate compounds Hv allowing the obtaining of -Hv radicals. Example Al: Al molecule Molecule 1: Product obtained by the reaction between Fmoc-Lys(Fmoc)-OH and 2-Cl-trityl chloride resin. [000657] To a suspension of Fmoc-Lys(Fmoc)-OH (7.32 g, 12.40 mmol) in dichloromethane (60 mL) at room temperature, DIPEA (4.32 mL, 24.80 mmol) is added. After complete solubilization (10 min), the resulting solution is poured onto 2-Cl-trityl chloride resin previously washed with dichloromethane (100-200 mesh, 1% DVB, 1.24 mmol / g) (4.00 g, 4.96 mmol) in a reactor suitable for peptide synthesis on a solid support. After 2 h of stirring at room temperature, HPLC-grade methanol (0.8 mL / g resin, 3.2 mL) is added, and the mixture is stirred at room temperature for 15 min. The resin is filtered, washed successively with dichloromethane (3 x 60 mL), DMF (2 x 60 mL), dichloromethane (2 x 60 mL), isopropanol (1 x 60 mL) and dichloromethane (3 x 60 mL). Molecule 2 i Product obtained by the reaction between molecule 1 and a DMF / piperidine mixture 80:20. [000658] Molecule 1, previously washed with DMF, is treated with a DMF / piperidine 80:20 mixture (60 mL). After 30 min of stirring at room temperature, the resin is filtered, washed successively with DMF (3 x 60 mL), isopropanol (1 x 60 mL) and dichloromethane (3 x 60 mL). Molecule 3: Product obtained by the reaction between molecule 2 and Fmoc-Glu(OtBu)- OH . [000659] To a suspension of Fmoc-Glu(OtBu)-OH (10.55 g, 24.80 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 9.43 g, 24.80 mmol) in a 1:1 DMF / dichloromethane mixture (60 mL), DIPEA (8.64 mL, 49.60 mmol) is added. After complete solubilization, the resulting solution is poured onto molecule 2. After 2 h of stirring at room temperature, the resin is filtered and washed successively with DMF (3 x 60 mL), isopropanol (1 x 60 mL), and dichloromethane (3 x 60 mL). Molecule 4: Product obtained by the reaction between molecule 3 and a 50:50 DMF / morpholine mixture. [000660] Molecule 3, previously washed with DMF, is treated with a 50:50 DMF / morpholine mixture (60 mL). After 1 h 15 of stirring at room temperature, the resin is filtered, washed successively with DMF (3 x 60 mL), isopropanol (1 x 60 mL) and dichloromethane (3 x 60 mL). Molecule 5: Product obtained by the reaction between molecule 4 and molecule 11. [000661] By a process similar to that used for molecule 3 applied to molecule 4 and to molecule 11 (8.07 g, 24.80 mmol) in DMF (60 mL), molecule 5 is obtained. Molecule 6: Product obtained by the reaction between molecule 5 and a mixture of dichloromethane / l,l,l,3,3,3-hexafluoro-2-propanol (HFIP) 80:20. [000662] Molecule 5 is treated with a dichloromethane / 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) mixture 80:20 (60 mL). After 20 min of stirring at room temperature, the resin is filtered and washed with dichloromethane (2 x 60 mL). The solvents are evaporated under reduced pressure. Two co-evaporations are then performed on the residue, first with dichloromethane (60 mL) and then with diisopropyl ether (60 mL). The product is purified by silica gel chromatography (dichloromethane, methanol). A white solid of molecule 6 is obtained. Yield: 2.92 g (52% over 6 steps) *H NMR (CD3OD, ppm): 0.90 (6H); 1.22-2.47 (88H); 3.13-3.25 (2H); 3.45-3.76 (4H); 4.24-4.55 (5H). LC / MS (ESI+): 1131.9 (calculated ([M+H] + ) : 1131.8). Molecule 7 1 Product obtained by the reaction between molecule 6 and N-Boc ethylenediamine. [000663] To a solution of molecule 6 (2.82 g, 2.49 mmol) in Me-THF (20 mL) at room temperature, I-V-hydroxybenzotriazole (HOBt, 496 mg, 3.24 mmol) and I-V-Boc ethylenediamine (BocEDA, 440 mg, 2.74 mmol) are successively added. The mixture is cooled to 0 °C, and then (3-dimethylaminopropyl)- / V'-ethylcarbodiimide hydrochloride (EDC, 621 mg, 3.24 mmol) is added. The reaction mixture is stirred for 15 min at 0 °C and then for 18 h at room temperature. The organic phase is diluted with dichloromethane (30 mL) and washed with saturated aqueous NH4Cl solution (2 x 20 mL), saturated aqueous NaHCC solution (2 x 20 mL), and saturated aqueous NaCl solution (2 x 20 mL). The organic phase is dried over a2SO4, filtered, and concentrated under reduced pressure. A white solid of molecule 7 is obtained after recrystallization in acetonitrile. Yield: 2.47 g (78%) *H NMR (CDCI3, ppm): 0.87 (6H); 1.09-1.77 (77H); 1.84-2.49 (20H); 2.99-3.83 (10H); 4.16-4.25 (1H); 4.27-4.47 (4H); 5.68 (0.1H); 5.95-6.08 (0.9H); 6.91-7.14 (2H); 7.43-7.57 (1H); 7.68-7.78 (1H); 8.22-8.35 (1H). LC / MS (ESI+): 1273.9 (calculated ([M+H] + ): 1273.9). Molecule Al [000664] To a solution of molecule 7 (2.47 g, 1.94 mmol) in dichloromethane A 4 N HCl solution in dioxane (7.27 mL) is added to a 20 mL sample at room temperature, and the mixture is stirred for 16 h at room temperature. After concentration under reduced pressure, co-evaporation, and washing with diisopropyl ether, a white solid of the Al molecule as the HCl salt is obtained. This solid is dissolved in water (100 mL), and the pH is adjusted to 7 by adding a 1 N aqueous NaOH solution. The solution is lyophilized, and the lyophilized product is dried by co-evaporation with toluene. A white solid of the Al molecule is obtained. Yield: 1.64 g (80%) *H NMR (D2O, ppm): 0.90 (6H); 1.15-2.59 (70H); 3.06-3.86 (10H); 4, 19-4.43 (5H). LC / MS (ESI+): 1061.8 (calculated ([M+H] + ): 1061.8). Example A2: molecule A2 Molecule 8: Product obtained by coupling between myristic acid and methyl L-glutamate. [000665] To a solution of myristic acid (35.0 g, 153.26 mmol) in tetrahydrofuran (THF, 315 mL) at 0 °C, N-hydroxysuccinimide (NHS, 17.81 g, 154.79 mmol) and N,N-dicyclohexylcarboxydiimide (DCC, 31.94 g, 154.79 mmol) are successively added. The mixture is stirred for 48 h while the temperature is raised to room temperature, filtered through a sintered filter, and then added to a solution of L-methyl glutamate (24.95 g, 154.79 mmol) and N,N-diisopropylethylamine (DIPEA, 99.0 g, 766.28 mmol) in water (30 mL). The reaction mixture is stirred at 20 °C for 48 h and then concentrated under reduced pressure. Water (200 mL) is added, and the resulting mixture is treated by successively adding ethyl acetate (AcOEt, 100 mL) followed by a 5% aqueous solution of NazCCh (50 mL). The aqueous phase is then washed again with AcOEt (100 mL), acidified by adding a 10% aqueous solution of HCl, and the product is extracted with dichloromethane (DCM, 3 x 150 mL).The organic phase is dried over a2SO4, filtered and concentrated under reduced pressure. A white solid of molecule 8 is obtained. Yield: 47.11 g (84%) *H NMR (CDC, ppm): 0.87 (3H); 1.07-1.66 (10 p.m.); 2.02-2, 11 (1H); 2.18-2.36 (3H); 2.39-2.47 (1H); 2.50-2.58 (1H); 3.69 (3H); 4.54-4.59 (1H); 6.62 (1H); 8.26 (1H). LC / MS (ESI+): 372.2 (calculated ([M+H] + ) : 372.3). Molecule 9: Product obtained by coupling between molecule 8 and methyl L-glutamate. [000666] By a process similar to that used for the preparation of molecule 8 and applied to molecule 8 (35.0 g, 94.21 mmol) and to methyl L-glutamate (15.33 g, 95.15 mmol), a white solid of molecule 9 is obtained after recrystallization in acetonitrile. Yield: 24.0 g (49%) NMR !H (DMSO-d6, ppm): 0.85 (3H); 1.06-1.51 (10 p.m.); 1.70-1.94 (3H); 1.96-2.15 (3H); 2.29-2.40 (4H); 3.58 (3H); 3.58 (3H); 4.16-4.22 (1H); 4.25-4.32 (1H); 7.93 (1H); 8, 16 (1H); 12.66 (1H) . LC / MS (ESI+): 515.3 (calculated ([M + H] + ): 515.3). Molecule 10; Product obtained by coupling between molecule 9 and N-Boc ethylenediamine. [000667] To a suspension of molecule 9 (24.0 g, 46.63 mmol) in DCM (285 mL) at 0 °C, HOBt (714 mg, 46.66 mmol), BocEDA (8.97 g, 55.96 mmol) in solution in DCM (25 mL), and then EDC (9.83 g, 51.30 mmol) are successively added. The reaction mixture is stirred for 1 h at 0 °C and then for 18 h at room temperature. The organic phase is washed with a saturated aqueous solution of NaHCO3 (2 x 300 mL), an aqueous solution of 1 N HCl (2 x 300 mL), and a saturated aqueous solution of NaCl (500 mL). Methanol (40 mL) is added, the organic phase is dried over Na2SO4, filtered, and concentrated under reduced pressure. A white solid of molecule 10 is obtained after recrystallization in acetonitrile. Yield: 27.15 g (89%) NMR !H (CDCh, ppm): 0.87 (3H); 1.07-1.68 (22H); 1.42 (9H); 1.97-2.18 (4H); 2.22-2.31 (2H); 2.35-2.55 (4H); 3, 19-3.29 (2H); 3.30-3.38 (2H); 3.66 (3H); 3.68 (3H); 4.34-4.41 (1H); 4.42-4.48 (1H); 5.54 (1H); 6.99-7.18 (2H); 7.56 (1H). LC / MS (ESI+): 657.4 (calculated ([M+H] + ) : 657.4). Molecule A2 [000668] A solution of molecule 10 (27.15 g, 41.33 mmol) in a DCM / methanol mixture (410 mL) at 0 °C is combined with a solution of 4 N HCl in dioxane (51.7 mL), and the mixture is stirred for 2 h at 0 °C and then for 16 h at room temperature. After concentration under reduced pressure and co-evaporation with methanol (2 x 150 mL), a white solid of molecule A2 in the form of a hydrochloride salt is obtained after recrystallization in acetonitrile. Yield: 23.2 g (95%) NMR !H (DMSO-d6, ppm): 0.85 (3H); 1.05-1.52 (22H); 1.71-1.85 (2H); 1.87-2.03 (2H); 2.07-2, 18 (2H); 2.24-2.37 (4H); 2.84 (2H); 3.24-3.38 (2H); 3.58 (3H); 3.58 (3H); 4, 17-4,24 (2H); 7.95-8.08 (5H); 8, 14 (1H). LC / MS (ESI+): 557.3 (calculated ([M + H] + ) : 557.4), Example A3: molecule A3 Molecule 11: Product obtained by the reaction between myristoyl chloride and L-proline. [000669] To a solution of L-proline (300.40 g, 2.61 mol) in 2 N aqueous sodium hydroxide (1.63 L) at 0 °C, myristoyl chloride (322 g, 1.30 mol) in dichloromethane (DCM, 1.63 L) is slowly added over 1 h. At the end of the addition, the reaction mixture is brought back to 20 °C over 3 h, then stirred for an additional 2 h. The mixture is cooled to 0 °C, and then a 37% aqueous HCl solution (215 mL) is added over 15 min. The reaction mixture is stirred for 1 h between 0 °C and 20 °C. The organic phase is separated, washed with a 10% aqueous HCl solution (3 x 430 mL), a saturated aqueous NaCl solution (430 mL), dried over Na₂SO₄, filtered through cotton, and then concentrated under reduced pressure. The residue is dissolved in heptane (1.31 L) at 50 °C, and the solution is then gradually brought to room temperature.After initiating crystallization using a glass rod, the medium is heated again to 40 °C for 30 min and then brought back to room temperature for 4 h. A white solid is obtained after filtration through a sintered slurry, washing with heptane (2 x 350 mL) and drying under reduced pressure. Yield: 410 g (97%) *H NMR (CDCIa, ppm): 0.88 (3H); 1.28 (20H); 1.70 (2H); 1.90-2.10 (3H); 2.36 (2H); 2.51 (1H); 3.47 (1H); 3.56 (1H); 4.61 (1H). LC / MS (ESI): 326.4; 651.7; (calculated ([M+H] + ) : 326.3 ; ([2M+H] + ) : 651.6). Molecule 12: Product obtained by coupling between molecule 11 and methyl L-glutamate. [000670] By a process similar to that used for the preparation of molecule 8 and applied to molecule 11 (30.0 g, 92.17 mmol) and to methyl L-glutamate (15.60 g, 96.78 mmol), a white solid of molecule 12 is obtained after solubilization in refluxing acetone, cooling to room temperature, and filtration through a sintered slurry. The filtrate is evaporated, and the residue is precipitated in acetone as before, this operation being repeated three times. Yield: 15.5 g (36%) *H NMR (DMSO-d6, ppm): 0.85 (3H); 1.07-1.37 (20H); 1.40-1.50 (2H); 1.71-2.27 (8H); 2.30-2.40 (2H); 3.28-3.54 (2H); 3.58 (1.3H); 3.59 (1.7H); 4.14-4.28 (1H); 4.28-4.37 (1H); 8.06 (0.55H); 8.33 (0.45H); 12.64 (1H). LC / MS (ESI+): 469.2 (calculated ([M+H] + ) : 469.3). Molecule 13: Product obtained by coupling between molecule 12 and N-Boc ethylenediamine. [000671] By a process similar to that used for the preparation of molecule 10 and applied to molecule 12 (15.5 g, 33.05 mmol) and to BocEDA (5.83 g, 36.36 mmol), a white solid of molecule 13 is obtained after recrystallization in acetonitrile. Yield: 19.8 g (83%) *H NMR (DMSO-d6, ppm): 0.85 (3H); 1.07-1.55 (10 p.m.); 1.37 (9H); 1.69-2, 19 (7H); 2.22-2.36 (3H); 2.91-3.17 (4H); 3.28-3.60 (5H); 4, 11-4, 18 (0.7H); 4.20-4.28 (1H); 4.38-4.42 (0.3H); 6.74 (1H); 7.64 (0.7H); 7.87 (0.7H); 7.98 (0.3H); 8.22 (0.3H). LC / MS (ESI+): 611.4 (calculated ([M+H]÷): 611.4). Molecule A3 [000672] By a process similar to that used for the preparation of molecule A2 and applied to molecule 13 (16.8 g, 27.50 mmol), a white solid of molecule A3 in the form of a hydrochloride salt is obtained after recrystallization in acetonitrile. Yield: 13.5 g (90%) *H NMR (DMSO-d6, ppm): 0.85 (3H); 1.08-1.52 (10 p.m.); 1.70-2.37 (10H); 2.80-2.90 (2H); 3.22-3.62 (4H); 3.57 (3H); 4.15-4.28 (1.75H); 4.41-4.44 (0.25H); 7.81-8.13 (4.51-1); 8.24-8.29 (0.25H); 8.33-8.39 (0.25H). LC / MS (ESI+): 511.3 (calculated ([M+H] + ): 511.4). Example A4: Molecule A4 Molecule 14: Product obtained by the reaction between lauroyl chloride and L-proline [000673] By a process similar to that used for the preparation of molecule 11 and applied to lauroyl chloride (27.42 g, 685.67 mmol) and L-proline (60.0 g, 247.27 mmol), a white solid of molecule 14 is obtained. Yield: 78.35 g (96%) NMR (CDCb, ppm): 0.87 (3H); 1.26 (16H); 1.70 (2H); 1.90-2.10 (3H); 2.35 (2H); 2.49 (1H); 3.48 (1H); 3.56 (1H); 4.60 (1H). LC / MS (ESI+): 298.1 (calculated ([M + H] + ): 298.2). Molecule 15 i Product obtained by coupling between molecule 14 and methyl L-glutamate. [000674] By a process similar to that used for the preparation of molecule 8 and applied to molecule 14 (34.64 g, 116.46 mmol) and to methyl L-glutamate (19.14 g, 118.79 mmol), a white solid of molecule 15 is obtained after recrystallization in acetonitrile. Yield: 37.28 g (73%) NMR X H (CDCb, ppm): 0.85 (3H); 1.08-1.42 (16H); 1.54-1.06 (2H); 1.80-2.47 (10H); 3.42-3.80 (2H); 3.65 (2.55H); 3.67 (0.45H); 4.37-4.40 (0.15H); 4.51-4.58 (0.85H); 4.58-4.67 (1H); 7.26 (0.15H); 7.65 (0.85H); 8.06 (1H). LC / MS (ESI+): 441.1 (calculated ([M+H] + ) : 441.3). Molecule 16: Product obtained by coupling between molecule 15 and / V-Boc ethylenediamine. [000675] By a process similar to that used for the preparation of molecule 10 and applied to molecule 15 (37.30 g, 84.66 mmol) and to BocEDA (14.92 g, 93.13 mmol), a white solid of molecule 16 is obtained after recrystallization in acetonitrile. Yield: 43.10 g (87%) *H NMR (DMSO-d6, ppm): 0.85 (3H); 1.08-1.53 ​​(18H); 1.37 (9H); 1.70-2.36 (10H); 2.91-3.60 (9H); 4.11-4.18 (0.7H); 4.21-4.28 (1H); 4.38-4.42 (0.3H); 6.38 (0.1H); 6.74 (0.9H); 7.65 (0.7H); 7.87 (0.7H); 7.99 (0.3H); 8.22 (0.3H). LC / MS (ESI+): 583.4 (calculated ([M+H] + ): 583.4). Molecule A4 [000676] By a process similar to that used for the preparation of molecule A2 and applied to molecule 16 (43.10 g, 73.96 mmol), a white solid of molecule A4 in the form of a hydrochloride salt is obtained after recrystallization in acetonitrile. Yield: 31.90 g (83%) *H NMR (DMSO-d6, ppm): 0.85 (3H); 1.05-1.37 (4 p.m.); 1.39-1.52 (2H); 1.70-2.37 (10H); 2.29-2.91 (2H); 3.20-3.62 (7H); 4.16-4.29 (1.7H); 4.42-4.46 (0.3H); 7.86-8.18 (4.6H); 8.32 (0.3H); 8.40 (0.3H). LC / MS (ESI+): 483.2 (calculated ([M + H] + ) : 483.3). Example A5: molecule A5 Molecule 17: Product obtained by the reaction between l-amino-4,7,10-trioxa-13-tridecane amine and tert-butyl phenylcarbonate. [000677] To a solution of l-amino-4,7,10-trioxa-13-tridecane amine (112.29 g, 509.71 mmol) in ethanol (510 mL) at 80 °C, tert-butyl phenylcarbonate (49.50 g, 254.86 mmol) is added dropwise. The reaction mixture is stirred at 80 °C for 3.5 h and then concentrated under reduced pressure. The residue is dissolved in water (250 mL), the pH is adjusted to 2.3 with a 37% HCl solution, and the mixture is extracted with methyl tert-butyl ether (MTBE, 2 x 150 mL). The aqueous phase is made basic to pH 12.6 by the addition of a 2 N NaOH solution and extracted with DCM (3 x 250 mL). The organic phase is washed with a 1 N aqueous NaOH solution (1 x 100 mL), a saturated aqueous NaCl solution (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. A yellow oil with molecule 17 is obtained. Yield: 54.4 g (67%) NMR ! H (CDCb, ppm): 1.40-1.58 (11H); 1.73-1.81 (4H); 2.80-2.84 (2H); 3.20-3.70 (2 p.m.); 5.11 (1H). LC / MS (ESI+): 321.2 (calculated ([M + H] + ): 321.2). Molecule 18; Product obtained by coupling between molecule 12 and molecule 17. [000678] By a process similar to that used for the preparation of molecule 10 and applied to molecule 12 (20.46 g, 43.66 mmol) and molecule 17 (16.79 g, 52.39 mmol), a white wax of molecule 18 is obtained after purification by flash chromatography (eluent: DCM, methanol), solubilization of the residue in DCM (300 mL), washing of the organic phase with an aqueous solution of NaHCCh (2 x 150 ml_), an aqueous solution of 10% HCl (2 x 150 ml_), a saturated aqueous solution of NaCl (2 x 150 mL), drying on Na2SO4 and concentration under reduced pressure. Yield: 30.15 g (90%) *H NMR (DMSO-d6, ppm): 0.85 (3H); 1.09-1.52 (31H); 1.55-1.67 (4H); 1.69-2.36 (10H); 2.91-2.98 (2H); 3.02-3.17 (2H); 3.28-3.61 (5 p.m.); 4.12-4.17 (0.7H); 4.20-4.28 (1H); 4.39-4.42 (0.3H); 6.37 (0.1H); 6.71 (0.9H); 7.59 (0.7H); 7.85 (0.7H); 7.94 (0.3H); 8.21 (0.3H). LC / MS (ESI+): 771.4 (calculated ([M + H] + ): 771.5). Molecule A5 [000679] By a process similar to that used for the preparation of molecule A2 and applied to molecule 18 (30.0 g, 38.91 mmol), a white solid of molecule A5 in the form of a hydrochloride salt is obtained after solubilization of the residue in water (500 mL) and lyophilization. Yield: 25.2 g (91%) *H NMR (DMSO-d6, ppm): 0.85 (3H); 1.06-1.37 (20H); 1.39-1.52 (2H); 1.58-1.66 (2H); 1.70-2.37 (12H); 2.78-2.85 (2H); 3.01-3.15 (2H); 3.31-3.62 (5 p.m.); 4.11-4.17 (0.7H); 4.19-4.27 (1H); 4.41-4.44 (0.3H); 7.63-7.71 (0.7H); 7.90-8.24 (4H); 8.28-8.35 (0.3H). LC / MS (ESI+): 671.4 (calculated ([M+H] + ) : 671.5). Example A7: molecule A7 Molecule 21: Product obtained by coupling between molecule 11 and L-lysine. [000680] By a process similar to that used for the preparation of molecule 8 applied to molecule 11 (133.00 g, 408.61 mmol) and to L-lysine (31.36 g, 214.52 mmol), a white solid of molecule 21 is obtained after crystallization twice in acetone. Yield: 106.50 g (68%) NMR ^ (DMSO-de, ppm): 0.85 (6H); 1.26 (40H); 1.35-1.50 (6H); 1.50-2.10 (10H); 2.10-2.25 (4H); 3.01 (2H); 3.31-3.55 (4H); 4.10-4.40 (3H); 7.68 (0.6H); 7.97 (1H); 8.27 (0.4H); 12.50 (1H). LC / MS (ESI): 761.8; (calculated ([M+H] + ) : 762.1). Molecule 22: Product obtained by coupling between molecule 21 and methyl / V-Boc-L-lysinate. [000681] By a process similar to that used for the preparation of molecule 10 applied to molecule 21 (43.00 g, 56.50 mmol) in solution in THF and in methyl / V-Boc-L-lysinate hydrochloride (20.12 g, 67.79 mmol), a transparent solid of molecule 22 is obtained and used without further purification. Yield: 55.80 g (98%) *H NMR (DMSO-d6, ppm): 0.86 (6H); 1.08-2.03 (64H); 1.37 (9H); 2.07-2.30 (4H); 2.84-3.09 (4H); 3.29-3.57 (4H); 3.58-3.65 (3H); 4, 14-4.43 (4H); 6.40 (0.1H); 6.74 (0.9H); 7.69 (0.6H); 7.82 (0.6H); 7.95-8.06 (1H); 8.11-8.20 (0.4H); 8.26 (0.4H). LC / MS (ESI): 1003.8 (calculated ([M +H] + ) : 1003.8) . Molecule 23: Product obtained by saponification of molecule 23. [000682] A solution of molecule 22 (55.80 g, 55.61 mmol) in a 1:1 TH F / water mixture (370 mL) at 0 °C is treated by the slow addition of a LiOH solution (2.00 g, 83.41 mmol) in water (185 mL). After 16 h of stirring at 0 °C, the mixture is concentrated under reduced pressure and the residue is resuspended in water (500 mL). DCM (500 mL) is added, the heterogeneous mixture is cooled to 10 °C and acidified by adding a 10% aqueous HCl solution to pH 1. The aqueous phase is extracted with DCM (2 x 300 mL), the combined organic phases are washed with a saturated aqueous NaCl solution (2 x 300 mL), dried over Na₂SO₄, filtered, and concentrated under reduced pressure. A white solid of molecule 23 is obtained after crystallization in acetone. Yield: 46.10 g (84%) *H NMR (pyridine-d6, ppm): 0.85 (6H); 1.05-2.03 (67H); 2.07-2.61 (10H); 3.12-3.93 (8H); 4.54-4.93 (2H); 4.98-5.16 (2H); 7.35-7.45 (1H); 8.34-8.63 (1H); 8.94-9.41 (2H). LC / MS (ESI): 989.8 (calculated ([M+H] + ): 989.8). Molecule A7 [000683] A solution of molecule 23 (12.00 g, 12.13 mmol) in dichloromethane (40 mL) at 0 °C is combined with a solution of 4 N HCl in dioxane (15.20 mL), and the mixture is stirred for 15 h at 0 °C and 5 h at room temperature. The reaction mixture is concentrated under reduced pressure, and the residue is dissolved in a mixture of DCM (120 mL) and 2 N NaOH (60 mL). After phase separation, the organic phase is washed with 2 N NaOH (60 mL), dried over Na₂SO₄, and concentrated under reduced pressure. Yield: 10.90 g (98%) RM *H (DMSO-d6, ppm): 0.86 (6H); 1.05-2.27 (70H); 2.45-2.52 (2H); 2.90-3.58 (6H); 3.67-3.76 (1H); 4.02-4.10 (0.6H); 4.11-4.17 (0.4H); 4.20-4.26 (0.6H); 4.30-4.39 (1H); 4.42-4.46 (0.4H); 7.29-7.42 (1H); 7.71-7.80 (0.6H); 7.97-8.05 (0.6H); 8.10-8.24 (0.4H); 8.33-8.45 (0.4H). [000684] LC / MS (ESI): 887.7 (calculated ([MH]): 887.7). Example A5a: molecule A5a Molecule 3a: Product obtained by the reaction between Fmoc-Lys(Fmoc)-OH and 2-Cl-trityl chloride resin. [000685] To a suspension of Fmoc-Lys(Fmoc)-OH (7.32 g, 12.40 mmol) in DCM (60 mL) at room temperature, DIPEA (4.32 mL, 24.80 mmol) is added. After complete solubilization (10 min), the resulting solution is poured onto resin 2-Cl-trityl chloride (100-200 mesh, 1% DVB, 1.24 mmol / g) (4.00 g, 4.96 mmol) previously washed with DCM, in a reactor suitable for peptide synthesis on solid supports. After 2 h of stirring at room temperature, HPLC-grade methanol (0.8 mL / g resin, 3.2 mL) is added and the medium is stirred at room temperature for 15 min. The resin is filtered and washed successively with DCM (3 x 60 mL), DMF (2 x 60 mL), DCM (2 x 60 mL), isopropanol (1 x 60 mL), and DCM (3 x 60 mL). Molecule 4a: Product obtained by reaction between molecule 3a and a DMF / piperidine mixture 80:20. [000686] Molecule 3a, previously washed with DMF, is treated with a mixture DMF / piperidine 80:20 (60 mL). After 30 min of stirring at room temperature, the resin is filtered, washed successively with DMF (3 x 60 mL), isopropanol (1 x 60 mL) and DCM (3 x 60 mL). Molecule 5a: Product obtained by reaction between molecule 4a and 8-(9-Fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (Fmoc-020c-OH). [000687] To a suspension of Fmoc-O20c-OH (9.56 g, 24.80 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 9.43 g, 24.80 mmol) in a 1:1 DMF / DCM mixture (60 mL), DIPEA (8.64 mL, 49.60 mmol) is added. After complete solubilization, the resulting solution is poured onto molecule 4a. After 2 h of stirring at room temperature, the resin is filtered and washed successively with DMF (3 x 60 mL), isopropanol (1 x 60 mL), and dichloromethane (3 x 60 mL). Molecule 6a: Product obtained by reaction between molecule 5a and a DMF / piperidine mixture 80:20. [000688] By a process similar to that used for molecule 4a applied to molecule 5a, molecule 6a is obtained. Molecule 7a: Product obtained by reaction between molecule 6a and lauric acid. By a process similar to that used for molecule 5a applied to molecule 6a and lauric acid (4.97 g, 24.80 mmol) in DMF (60 mL), molecule 7a is obtained. Molecule 8a: Product obtained by reaction between molecule 7a and a mixture of dichloromethane / l,l,l,3,3,3-hexafluoro-2-propanol (HFIP) 80:20. [000689] Molecule 7a is treated with a dichloromethane / 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) mixture 80:20 (60 mL). After 20 min of stirring at room temperature, the resin is filtered and washed with dichloromethane (2 x 60 mL). The solvents are evaporated under reduced pressure. Two co-evaporations are then performed on the residue, first with dichloromethane (60 mL) and then with diisopropyl ether (60 mL). A white solid of molecule 8a is obtained after recrystallization in acetonitrile. Yield: 2.63 g (66% over 6 steps) NMR !H (CDCb, ppm): 0.87 (6H); 1.09-1.66 (40H); 1.77-1.98 (2H); 2.13-2.29 (4H); 3.24-3.75 (18H); 3.95-4.07 (4H); 4.65-4.70 (1H); 6.23-6.37 (1 H); 6.39-6.62 (1H); 6.74-6.91 (1H); 7.38-7.54 (1H). LC / MS (ESI): 801.6 (calculated ([M +H] + ): 801.6). Molecule 9a: Product obtained by the reaction between molecule 8a and N-Boc ethylenediamine. [000690] To a solution of molecule 8a (2.63 g, 3.29 mmol) in chloroform (20 mL) at room temperature, HOBt (654 mg, 4.27 mmol) and BocEDA (580 mg, 3.62 mmol) are successively added. The mixture is cooled to 0 °C and then EDC (819 mg, 4.27 mmol) is added. The reaction mixture is stirred for 15 min. The organic phase was incubated at 0 °C and then at room temperature for 18 hours. It was washed with a saturated aqueous solution of IMH-I (2 x 10 mL), a saturated aqueous solution of NaHCl (2 x 10 mL), and a saturated aqueous solution of NaCl (2 x 10 mL). The organic phase was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. A white solid of molecule 9a was obtained after purification by silica gel chromatography (eluent: dichloromethane, methanol). Yield: 2.37 g (76%) NMR 'Ή (CDCh, ppm): 0.87 (6H); 1.08-1.47 (34H); 1.43 (9H); 1.48-1.70 (7H); 1.78-1.87 (1H); 2.14-2.25 (4H); 3, 16-3.71 (22H); 3.92-4.04 (4H); 4.47-4.52 (1H); 5.33 (1H); 6.10 (1H); 6.65-7.01 (1H); 7.11-7.30 (2H); 7.47-7.63 (1H). A5a molecule [000691] A solution of molecule 9a (2.37 g, 2.51 mmol) in dichloromethane (50 mL) at room temperature is combined with a solution of 4 M HCl in dioxane (6.3 mL), and the mixture is stirred for 2 h at room temperature. After concentration under reduced pressure, the residue is dissolved in dichloromethane (50 mL) and then washed with 1 N NaOH (2 x 12.5 mL) and saturated NaCl (25 mL). The organic phase is dried over Na₂SO₄, filtered, and concentrated under reduced pressure. A white solid of molecule A5a is obtained after recrystallization in acetonitrile. Yield: 1.57 g (74%) *H NMR (CDCh, ppm): 0.87 (6H); 1.08-1.43 (34H); 1.48-1.71 (7H); 1.74-1.93 (3H); 2.14-2.25 (4H); 2.79-2.86 (2H); 3.17-3.71 (20H); 3.93-4.05 (4H); 4.47-4.54 (1H); 6.08-6.29 (1H); 6.84-7.01 (1H); 7.15-7.32 (2H); 7.50-7.64 (1H). LC / MS (ESI): 843.6 (calculated ([M + H] + ): 843.7). Example A6a: A6a molecule Molecule 10a: Product obtained by hydrogenation of retinoic acid. [000692] A solution of retinoic acid (19.0 g, 63.24 mmol) in methanol (450 mL) in the presence of 10% palladium on carbon (1.9 g) is placed under a hydrogen atmosphere (1 atm) at room temperature. After overnight, the reaction mixture is filtered through a sintered filter, and the filtrate is concentrated under reduced pressure. A colorless oil of molecule 10a is obtained. Yield: 19.50 g (99%) NMR ^ (CDCh, ppm): 0.45-2.01 (35 H); 2.10-2.17 (1H); 2.33-2.38 (1 H); 11.14 ( 1H) . LC / S (ESI): 309.3; (calculated ([MH] ): 309.3). Molecule l ia: Product obtained by coupling between Boc-l-amino-4,7,10-trioxa-13-tridecane amine (BocTOTA) and molecule 10a. [000693] By a process similar to that used for the preparation of molecule 9a applied to molecule 10a (19.3 g, 62.15 mmol) and to BocTOTA (23.9 g, 74.58 mmol), an orange oil of molecule l ia is obtained. Yield: 37.05 g (97%) *H NMR (CDCb, ppm): 0.43-1.71 (49 H); 2.13-2.17 (1H); 3.17-3.24 (2H); 3.32-3.39 (2H); 3.51-3.66 (12H); 4.77 (0.1H); 4.94 (0.9H); 6, 13 (0.9H); 6.29 (0.1H). LC / MS (ESI): 613.5; (calculated ([M+H] + ) : 613.5). A6a molecule [000694] By a process similar to that used for the preparation of molecule A5a applied to molecule lia (34.9 g, 56.94 mmol), an orange oil of molecule A6a is obtained. Yield: 28.5 g (97%) NMR 1 H (CDCb, ppm): 0.41-1.96 (42 H); 2.13 (1H); 2.78 (2H); 3.31-3.36 (2H); 3.53 (4H); 3.55-3.58 (4H); 3.60-3.63 (4H); 6.43 (1H) . LC / MS (ESI): 513.5; (calculated ([M+H]+ ) : 513.5). Example AS: AS molecule Molecule 15a: Product obtained by the reaction between decanoic acid and L-leucine. [000695] By a process similar to that used for the preparation of molecule 8 applied to decanoic acid (8.77 g, 50.94 mmol) and L-leucine (7.00 g, 53.36 mmol), a white solid of molecule 15a is obtained. Yield: 9.17 g (66%) *H NMR (DMSO-d6, ppm): 0.82-0.89 (9H); 1.18-1.65 (5 p.m.); 2.04-2, 14 (2H); 4, 19- 4,23 (1H); 7.98 (1H); 12.40 (1H). LC / MS (ESI): 286.2 (calculated ([M+H] + ) : 286.2) . Molecule 16a: Product obtained by the reaction between molecule 15a and the methyl ester of L-lysine. [000696] To a solution of molecule 15a (9.16 g, 32.11 mmol) in THF (160 mL) are successively added triethylamine (8.12 g, 80.27 mmol) and 2-(lH- Benzotriazol-l-yl)-l,l,3,3-tetramethyluronium tetrafluoroborate (TBTU) is added, and the mixture is stirred for 30 min at room temperature. L-lysine methyl ester dihydrochloride (3.93 g, 16.86 mmol) is added, and the reaction mixture is stirred for 3 h and then concentrated under reduced pressure. The residue is diluted with acetonitrile (200 mL), the organic phase is filtered and washed with 1 N aqueous HCl and then with water, dried over Na₂SO₄, filtered, and concentrated under reduced pressure. A white solid of molecule 16a is obtained after trituration of the residue in acetonitrile. Yield: 7.33 g (66%) H NMR (DMSO-d6, ppm): 0.80-0.91 (18H); 1.06-1.72 (38H); 2.03-2, 16 (4H); 2.91-3.07 (2H); 3.60 (1.15H); 3.61 (1.85H); 4.13-4.28 (2H); 4.33-4.44 (1H); 7.79-7.92 (3H); 8.13-8.26 (1H). LC / MS (ESI) 695.7 (calculated ((M + H] + ) : 695.6). Molecule 17a: Product obtained by the saponification of molecule 16a. (000697] To a solution of molecule 16a (7.33 g, 10.55 mmol) in a mixture THF / methanol / water (105 mL) is mixed with LiOH (505.13 mg, 21.09 mmol) at 0 °C, and the mixture is stirred for 20 h at room temperature and concentrated under reduced pressure. The aqueous phase is acidified with 1 N HCl solution to pH 1, and the resulting solid is filtered, washed with water, and dried under reduced pressure to yield a white solid of molecule 17a. Yield: 7.09 g (99%) NMR l H (DMSO-d6, ppm): 0.80-0.89 (18H); 1.18-1.73 (40H); 2.03-2.16 (4H); 2.91-3.05 (2H); 4.03-4.13 (1 H); 4.21-4.27 (1 H); 4.31-4.40 (1H); 7.79-8.02 (4H). LC / MS (ESI): 681.7 (calculated ((M +H] + ) : 681.6). Molecule 18a: Product obtained by the reaction between molecule 17a and N-Boc ethylenediamine. [000698] By a process similar to that used for the preparation of molecule 16a applied to molecule 17a (7.09 g, 10.41 mmol) and to N-Boc ethylenediamine (1.83 g, 11.45 mmol), a white solid of molecule 18a is obtained after trituration in acetonitrile. Yield: 6.64 g (77%) ppm): 0.80-0.91 (18H); 1.15-1.73 (49H); 2.03-2, 18 (4H); 2.92-3, 13 (6H); 4.05-4.30 (3H); 6.71-6.83 (1H); 7.69-8.23 (5H). LC / MS (ESI): 824.0 (calculated ( (M + H) + ): 823.7). Molecule A8 [000699] By a process similar to that used for molecule A5a applied to molecule 18a (3.00 g, 3.64 mmol) without basic washing, a beige solid of molecule A8 in the form of a hydrochloride salt is obtained after co-evaporation 4 times of the residue in methanol. Yield: 2.66 g (96%) NMR XH (DMSO-d6, ppm): 0.80-0.91 (18H); 1.15-1.76 (40H); 2.03-2, 19 (4H); 1.78-2.89 (2H); 2.91-3.07 (2H); 3.22-3.37 (2H); 4.08-4, 14 (1H); 4, 17-4.28 (2H); 7.81-8.36 (8H). LC / MS (ESI): 723.7 (calculated ([M+H] + ) : 723.6). Example A9: Molecule A9 Molecule 19a: 13-Methyltetradecanoic acid. [000700] In a dry three-necked flask under argon, magnesium shavings (5.50 g, 226.3 mmol) are introduced. The magnesium is covered with anhydrous THF (25 mL), and a few drops of l-bromo-2-methylpropane are added at room temperature to initiate the reaction. After observing an exothermic reaction and slight turbidity of the medium, the remaining l-bromo-2-methylpropane (28.42 g, 207 mmol), diluted in THF (60 mL), is added dropwise over 1 h while the temperature of the medium remains stable between 65 and 70 °C. The reaction medium is then heated under reflux for 2 h. [000701] In a three-necked flask under argon, a solution of CuCl₂ (280 mg, 2.83 mmol) dissolved in β-methylpyrrolidone (NMP) previously distilled at 0 °C is dropwise added to a solution of 11-bromoundecanoic acid (25 g, 94.27 mmol) dissolved in THF (60 mL). A slightly warmed solution of the organomagnesium compound diluted in THF (50 mL) is then dropwise added to this solution to maintain the temperature of the mixture below 25 °C. The mixture is then stirred at room temperature for 16 h. The medium is cooled to 0 °C and the reaction is stopped by the slow addition of a 1 N aqueous HCl solution until pH 1 is reached (300 mL). The medium is then extracted with hexane (100 mL) and ethyl acetate (2 x 75 mL). After washing the organic phase with a 1 N aqueous HCl solution (100 mL) and water (100 mL), and drying over a₂S₄ apparatus, the solution is filtered and concentrated under vacuum to give a brown solid.After purification by flash chromatography (cyclohexane, ethyl acetate), a white solid is obtained. Yield: 18.1 g (79%) NMR X H (CDCI3, ppm): 0.87 (6H); 1, 11-1,18 (2H); 1.20-1.38 (16H); 1.51 (1H); 1.63 (2H); 2.35 (2H) . Molecule 20: Product obtained by the reaction between molecule 19a and L-leucine. [000702] To a solution of molecule 19a (18.05 g, 74.46 mmol) in THF (745 mL) at room temperature, DCC (14.63 g, 70.92 mmol) and NHS (8.16 g, 70.92 mmol) are successively added. After 40 h of stirring at room temperature, the medium is cooled to 0 °C for 20 min and filtered through a sintered filter. L-leucine (9.77 g, 74.46 mmol), DIPEA (86 mL), and water (150 mL) are added to the filtrate. After 20 h of stirring at room temperature, the medium is diluted with a saturated aqueous solution of NaHCC (200 mL). The aqueous phase is washed with ethyl acetate (2 x 200 mL) and acidified with an aqueous solution of 2 N HCl to pH 1. The precipitate is filtered, rinsed thoroughly with water, and dried under vacuum at 50 °C. Three times, the solid is triturated in pentane, sonicated, and then filtered to give a white solid. Yield: 18.8 g (75%) NMR ^ (CDCb, ppm): 0.86 (6H); 0.96 (6H); 1.12-1.18 (2H); 1.20-1.78 (22H); 2.24 (2H); 4.58-4.63 (1H); 5.89 (1H). LC / MS (ESI): 356.2; (calculated ([M+H] + ) : 356.6). Molecule 21a: Product obtained by the reaction between molecule 20 and Boc-tri(ethyleneglycol)diamine. [000703] To a solution of molecule 20 (16.7 g, 46.97 mmol) in THF (235 mL), DIPEA (20.3 mL) and TBTU are added at room temperature. After 20 min of stirring, Boc-tri(ethyleneglycol)diamine (14 g, 56.36 mmol) is added. After stirring at room temperature for 5 h, the mixture is concentrated under vacuum. The residue is resuspended in ethyl acetate (500 mL), washed with a saturated aqueous solution of NaHCCb (3 x 200 mL), an aqueous solution of 1 N HCl (3 x 200 mL), and a saturated aqueous solution of NaCl (3 x 200 mL). After drying on Na2SO4, filtration and concentration under vacuum, the residue is purified by flash chromatography (cyclohexane, ethyl acetate, methanol) to give a colorless oil. Yield: 23.5 g (85%) NMR ! H (CDC, ppm): 0.86 (6H); 0.93 (6H); 1.10-1.17 (2H); 1.19-1.08 (31H); 2, 18 (2H); 3.23-3.65 (12H); 4.41-4.56 (1 H); 5.12-5.47 (1H); 5.99-6.11 (0.75H); 6.48-6.65 (1H); 7.30-7.40 (0.25H). Molecule A9 [000704] By a process similar to that used for the preparation of molecule A5a applied to molecule 21a (23.46 g, 40.04 mmol) without basic washing, the residue The solution obtained after concentration under vacuum is triturated in a mixture of a ketone, nitriIe / acetone. The supernatant is removed and the pasty residue is dried under vacuum. The residue is then triturated in acetone (150 mL) and the white solid of molecule A9, in the form of the hydrochloride salt, is filtered, rinsed with acetone, and then dried under vacuum. Yield: 13.0 g (64%) NMR X H (DMSO-d6, ppm): 0.79-0.90 (12H); 1.09-1.61 (24H); 2.03-2, 17 (2H); 2.92-2.98 (2H); 3, 15-3,23 (2H); 3.40 (2H); 3.50-3.58 (4H); 3.61 (2H); 4.30-4.23 (1H); 7.88-8.14 (5H). LC / MS (ESI): 486.4; (calculated ([M-CI] + ) : 486.8). Example AlO: AlO molecule Molecule 22a: Product obtained by the reaction between octanoyl chloride and L-proline. [000705] By a process similar to that used for the preparation of molecule 11 and applied to octanoyl chloride (150.0 g, 0.922 mol) and L-proline (212.3 g, 1.844 mol), a colorless oil of molecule 22a is obtained after washing the organic phase with an aqueous solution of 10% HCl (3 x 300 mL), a saturated aqueous solution of NaCl (300 mL), drying over Na2SO4, filtration through cotton, concentration under reduced pressure, then the residue is purified by flash chromatography (eluent: DCM, MeOH) Yield: 134 g (60%) *H NMR (CDC, ppm): 0.87 (3H); 1.10-1.52 (8H); 1.57-1.74 (2H); 1.79-2.52 (6H); 3.37-3.67 (2H); 4.37-4.42 (0.07H); 4.53-5.63 (0.93H); 9.83 (1H). LC / MS (ESI): 242.1; (calculated ([M+H] + ) : 242.2). Molecule 23a: Product obtained by coupling between molecule 22a and L-lysine. [000706] To a solution of molecule 22a (132 g, 0.547 mol) in THF (924 mL) cooled to a temperature below 5 °C, NHS (66.1 g, 0.574 mol) and DCC (118.5 g, 0.574 mol) are successively added. After 21 h of stirring, the precipitate is removed by precipitation, and the filtrate is added over 30 min to a solution of L-lysine (41.98 g, 0.287 mol) in a mixture of deionized water (82 mL) and DIPEA (476 mL, 2.735 mol) at 15 °C. After 23 h of stirring at room temperature, the reaction mixture is concentrated under reduced pressure to give an oily residue, which is then diluted in water (1.3 L). The aqueous phase is washed twice with AcOEt (2 x 0.5 L), cooled to a temperature below 10 °C, and acidified by adding a solution 120 mL of 6 N HCl was used to achieve a pH of 1, then extracted three times with DCM (3 x 0.6 L). The organic phases were combined, washed with a saturated NaCl solution (0.6 L), dried over Na₂SO₄, and then concentrated under reduced pressure. The resulting foam was refluxed in acetone (240 mL) for 2 hours. After overnight storage at 10 °C, pentane (240 mL) was added dropwise. After 1 hour of stirring, the precipitate was collected by vacuum filtration, washed with a 1:1 mixture of pentane and acetone (150 mL), and then dried under vacuum. Yield: 83.9 g (52%) *H NMR (CDCI3, ppm): 0.87 (6H); 1.06-1.78 (25H); 1.80-2.41 (1 p.m.); 2.80-3.72 (6H); 4.30-4.39 (0.15H); 4.46-4.70 (2.85H); 7.84 (1H); 7.93 (1H) . LC / MS (ESI): 593.5; (calculated ([M+H] + ): 593.4). Molecule 24: Product obtained by coupling between molecule 23a and the m ethyl ester of L-lysine. [000707] On molecule 23a (76.26 g, 0.129 mol) are successively added HOPO (3.57 g, 32.1 mmol), LysOMe dihydrochloride (15.0 g, 64.3 mmol), and EDC (34.53 g, 0.18 mol) are added, followed by DMF (600 mL) that has been previously cooled to 5 °C. After dissolution, triethylamine (43.9 mL, 0.315 mol) is added dropwise, maintaining the temperature below 5 °C for 2 hours after the addition is complete. After overnight cooling to room temperature, the reaction mixture is poured onto a water / ice mixture (2 kg) and DCM (0.5 L). After 15 minutes of stirring, the phases are separated. The aqueous phase is extracted twice with DCM (2 x 0.4 L). The organic phases are combined, washed with 0.5 L of 1 N HCl solution, then with 0.5 L of saturated NaCl solution, dried over Na₂SO₄, concentrated under reduced pressure, and the residue is purified by flash chromatography (eluent: DCM, MeOH). Yield: 56.7 g (67%) NMR XH (CDCb, ppm): 0.87 (12H); 1.10-2.40 (82H); 2.86-3.72 (5 p.m.); 4.16-4.60 (7H); 6.83-8.01 (6H). A10 molecule [000708] A solution of molecule 24 (4.0 g, 3.05 mmol) in ethylenediamine (30 mL) is heated to 50 °C overnight. The reaction mixture is then diluted with methyltetrahydrofuran, and the organic phase is washed four times with a saturated NaCl solution (4 x 30 mL) and then twice with water (2 x 50 mL) before being dried over Na₂SO₄ and then concentrated under reduced pressure. The residue is solubilized in acetonitrile under reflux for 30 min, and then the solution is cooled to temperature room temperature with stirring overnight. The white precipitate is then collected by vacuum filtration, washed with cold acetonitrile (2 x 20 mL), and then dried under vacuum. Yield: 3.0 g (74%) *H NMR (CDC, ppm): 0.87 (12H); 1.09-2.37 (84H); 2.74-4.56 (25H); 6.85-8.00 (7H). LC / MS (ESI): 1338.0 (calculated ([M+H]+ ) : 1338.0). Example Ai l: Ai l molecule [000709] The Ai l molecule is obtained by the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (40.0 g, 1.16 mol / g). The first amino acid, Fmoc~Lys(Fmoc)-OH (1.5 equivalents), was grafted in DCM (10V) in the presence of DIPEA (3.0 equivalents). Unreacted sites were capped with methanol (0.8 mL / g resin) at the end of the reaction. The couplings of protected amino acids Fmoc-Glu(OtBu)-OH (2.5 equivalents), Fmoc-Pro-OH (2.5 equivalents) and myristic acid (2.5 equivalents) are carried out in DMF (10V), in the presence of HATU (2.5 equivalents) and DIPEA (3.7 equivalents). [000710] The Fmoc protecting groups are removed using a DMF / piperidine 80:20 (10 V) solution. The product is cleaved from the resin using a DCM / HFIP 80:20 (10 V) solution. After concentration under reduced pressure, the residue is purified by silica gel chromatography (dichloromethane, methanol). Yield: 56.5 g (65%) H NMR (CD3OD, ppm): 0.90 (6H); 1.22-2.53 (140H); 3.12-3.25 (2H); 3.43-3.80 (4H); 4.17-4.54 (9H). LC / MS (ESI+): 1894.5 (calculated ([M+Na] + ) : 1894,2) , Example A12: Molecule A12 Molecule 25: Product obtained by hydrogenation of farnesol. [000711] To a solution of farnesol (60.00 g, 269.82 mmol) in THF (1200 mL) under argon, platinum oxide (PtCh, 613 mg, 2.70 mmol) is added and the medium is placed under 1 atm of dihydrogen and then stirred for 6 days at room temperature. After filtration through celite with THF rinsing, a black oil with molecule 25 is obtained after concentration under reduced pressure. This compound is used without further purification. Yield: 61.60 g (100%) *H NMR (CDCIa, ppm): 0.85 (3H); 0.87 (6H); 0.90 (3H); 1.01 -1.43 (15H); 1.47-1.66 (3H); 3.62-3.76 (2H). Molecule 26: Product obtained by oxidation of molecule 25 [000712] To a solution of molecule 25 (61.60 g, 269.68 mmol) in a dichloroethane / water mixture (1350 mL / 1080 mL), tetrabutylammonium bromide (46.95 g, 145.63 mmol), acetic acid (416 mL, 7.28 mol), and then KMnO4 (127.85 g, 809.04 mmol) are successively added in small fractions while maintaining the temperature between 11 and 13 °C. The reaction mixture is then stirred for 4.5 h under reflux, cooled to 0 °C, and acidified to pH 1 with a 37% HCl solution (50 mL). α2SO3 (186.94 g) is gradually added while maintaining the temperature between 0 and 10 °C, and the mixture is stirred until complete decolorization. The medium is acidified to pH 1 with a 37% HCl solution, then water (500 L) and DCM (500 mL) are added. The phases are separated, and the aqueous phase is extracted with DCM (2 x 500 mL).The combined organic phases are washed with a 10% aqueous HCl solution (400 mL), water (2 x 400 mL), and a saturated aqueous NaCl solution (400 mL), dried over a₂SO₄, filtered, and concentrated under reduced pressure. A yellow oil with molecule 26 is obtained after purification by flash chromatography (eluent: cyclohexane, AcOEt). Yield: 54.79 g (84%) NMR ! H (CDCh, ppm): 0.85 (3H); 0.87 (6H); 0.97 (3H); 1.03-1.43 (1 p.m.); 1.52 (1H); 1.91-2.01 (1H); 2, 11-2, 18 (1H); 2.32-2.39 (1H). LC / MS (ESI-): 241.3 (calculated ([MH]): 241.2). Molecule 27: Product obtained by coupling between molecule 26 and methyl L-prolinate. [000713] To a solution of molecule 26 (54.70 g, 225.66 mmol) in DCM (1500 mL) at 0 °C, HOBt (3.46 g, 22.57 mmol), DIPEA (117.92 mL, 676.97 mmol), methyl L-prolinate hydrochloride (56.06 g, 338.49 mmol), and then EDC (64.89 g, 338.49 mmol) are successively added. The reaction mixture is stirred. The medium was incubated at 0 °C for 1 h, then at room temperature for 18 h. It was then diluted with DCM (1000 mL) and washed with a saturated aqueous solution of NaHCCh (2 x 1 L), a 1 N aqueous solution of HCl (2 x 1000 mL), and a saturated aqueous solution of NaCl (2 x 1000 mL). The organic phase was dried over Na₂SO₄. 4» filtered and concentrated under reduced pressure to give a yellow oil of molecule 27 which is used without further purification. Yield: 77.15 g (97%) *H NMR (DMSO-de, ppm): 0.79-0.89 (12H); 0.98-1.43 (13H); 1.51 (1H); 1.70-2.32 (7H); 3.33-3.42 (0.4H); 3.46-3.57 (1.6H); 3.59 (2.4H); 3.67 (0.6H); 4.23-4.32 (0.8H); 4.53-4.62 (0.2H). LC / MS (ESI+): 354.2 (calculated ([M+H] + ): 354.3). Molecule 28: Product obtained by the saponification of molecule 27. [000714] A solution of molecule 27 (77.15 g, 218.22 mmol) in a 1:1 THF / MeOH mixture (1454 mL) at 0 °C is dropwise added a solution of LiOH (7.84 g, 327.33 mmol) in water (727 mL). The reaction mixture is stirred at 0 °C for 18 h and then at room temperature for 5 h. The organic solvents are evaporated under reduced pressure. Water (500 mL), a 10% aqueous HCl solution (200 mL), and DCM (800 mL) are added, and the phases are separated. The aqueous phase is extracted with DCM (2 x 1 L). The combined organic phases are washed with water (500 mL), a saturated aqueous solution of NaCl (500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow 28-molecule oil which is used without further purification. Yield: 71.72 g (97%) *H NMR (DMSO-de, ppm): 0.73-0.95 (12H); 0.95-1.42 (13H); 1.51 (1H); 1.65-2.32 (7H); 3.24-3.64 (2H); 4.13-4.28 (0.8H); 4.37-4.50 (0.2H); 12.44 (1 H). LC / MS (ESI+): 340.2 (calculated ([M+H] + ): 340.3). Molecule A12 [000715] Molecule A12 is obtained by the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (34.5 g, 1.16 mmol / g). [000716] The ethylenediamine (10.0 equivalents) grafting is carried out in DCM (10V), in the presence of DIPEA (10.0 equivalents). The unreacted sites are capped with methanol (0.8 mL / g resin) at the end of the reaction. [000717] Couplings of protected amino acids Fmoc-Lys(Fmoc)-OH (1.5 equivalents), Fmoc-Glu(OMe)-OH (3.0 equivalents) and molecule 28 (3.0 equivalents) are carried out in a DCM / DMF 1:1 (10V) mixture, in the presence of HATU (1.0 equivalent with respect to the acid) and DIPEA (2.0 equivalents with respect to the acid). [000718] The Fmoc protecting groups are removed using a DMF / piperidine 80:20 (10 V) solution (after coupling of lysine) or a 50% morpholine solution in DMF (after coupling of glutamic acids). [000719] The product is cleaved from the resin using a 50:50 DCM / TFA solution (10 V). After evaporation, the residue is solubilized in MeTHF (450 mL) and the organic phase is washed with a saturated aqueous solution of IMaHCO3 (3 x 450 mL) followed by a saturated aqueous solution of NaCl (200 mL). After drying over Na2SO4, the organic phase is filtered, concentrated under reduced pressure, and the residue is purified by silica gel chromatography (dichloromethane, methanol, NH4OH). Yield: 13.95 g (31% overall over 7 steps). *H NMR (DMSO-de, ppm): 0.73-0.91 (24H); 0.96-2.41 (56H); 2.72 (2H); 2.89-3.10 (2H); 3.15-3.26 (2H); 3.26-3.51 (4H); 3.57 (3H); 3.58 (3H); 3.99-4.50 (5H); 6.07 (2H); 7.59-8.39 (5H). LC / MS (ESI+): 1118.2 (calculated ([M+H] + ): 1117.8). Example A13: Molecule A13 Molecule 29: Product obtained by polymerization of y-benzyl-L-glutamate / V-carboxyanhydride initiated by / V-Boc-ethylenediamine. [000720] In a reactor, γ-benzyl-L-glutamate / V-carboxyanhydride (39.44 g, 149.82 mmol) is dissolved in DMF (81 mL) at 25 °C. The mixture is then stirred until completely dissolved, cooled to -10 °C, and then a solution of BocEDA (6.00 g, 37.45 mmol) in DMF (7 mL) is rapidly introduced. The reaction mixture is stirred at 0 °C for 3 h, and then a solution of HCl in 1,4-dioxane (3.33 M, 11.8 mL, 39.29 mmol) is added. The reaction mixture is stirred at room temperature and then poured onto a MeOH / IPE solution (125 mL / 495 mL) cooled by an ice bath. After 65 h of stirring at room temperature, the precipitate is filtered on a sintered sinter, washed with IRE (2 x 90 mL) and dried at 30 °C under reduced pressure. Yield: 21.71 g (54%) DP (estimated from NMR) C H): 4.9 The calculated average molar mass of molecule 29 in hydrochloride salt form is 1270.9 g / mol. *H NMR (DMSO-d6, ppm): 1.35 (9H); 1.72-2.09 (9.8H); 2.23-2.60 (9.8H); 2.86-3.19 (4H); 3.85 (1H); 4.14-4.52 (3.9H); 4.86-5.23 (9.8H); 6.33-6.85 (1H); 7.09-7.55 (24.5H); 7.88-8.42 (6.9H); 8.67 (1H). Molecule 30: Product obtained between the coupling of myristoyl chloride and molecule 29. [000721] After solubilizing molecule 29 as its hydrochloride salt (12.46 g, 9.80 mmol) in DCM (115 mL), the solution is cooled to 0 °C. Triethylamine (2.35 g, 23.24 mmol) and a myristoyl chloride solution (3.16 g, 12.79 mmol) are then successively added to DCM (16 mL). The reaction mixture is stirred at 0 °C for 4 h and then at room temperature for 2 h before being poured onto 110 mL of ... Yield: 9.77 g (69%) DP (estimated from *H NMR): 5.1 The calculated average molar mass of molecule 30 is 1488.7 g / mol. *H NMR (CDCI3, ppm): 0.87 (3H); 1.07-1.51 (29H); 1.51-1.64 (2H); 1.80-2.75 (22.4H); 2.98-3.73 (4H); 3.84-4.50 (5.1H); 4.86-5.32 (10.2H); 5.71-6.47 (1H); 6.72-8.38 (31, 6H). Molecule A13 [000722] A solution of molecule 30 (4.70 g, 3.16 mmol) in DCM (31 mL) at 0 °C is mixed with TFA (31 mL). The reaction mixture is stirred at 0 °C for 2 h and then concentrated under reduced pressure and at room temperature. The residue is resuspended in DCM (100 mL) and then concentrated to dryness under reduced pressure and at room temperature. The residue is solubilized in DCM (100 mL) and washed with a solution The organic solution was treated with aqueous carbonate buffer at pH 10.4 (326 mL followed by 2 x 200 mL) and then with aqueous HCl solution (0.1 mL, 2 x 200 mL). The organic solution was dried over Na₂SO₄, filtered, and then concentrated to dryness at 40 °C under reduced pressure. Yield: 3.96 g (88%) DP (estimated from NMR) J H): 5.2 The calculated average molar mass of the A13 molecule in hydrochloride salt form is 1446.9 g / mol. *H NMR (TFA-d, ppm): 0.91 (3H); 1.17-1.47 (20H); 1.60-1.74 (2H); 1.99-2.78 (22.8H); 3.41-4.05 (4H); 4.62-4.83 (5.2H); 5.05-5.35 (10.4H); 6.99-8.02 (26H). Example A14: Molecule A14 Molecule 31: Product obtained by the reaction between molecule 14 and Boc-ethylenediamine. [000723] By a process similar to that used for the preparation of molecule 10, applied to molecule 14 (12.00 g, 40.35 mmol) and to BocEDA (7.76 g, 48.42 mmol), a colorless oil of molecule 31 is obtained and used without further purification. Yield: 17.40 g (94%) *H NMR (CDC, ppm): 0.86 (3H); 1.11-1.68 (18H); 1.41 (9H); 1.80-2.38 (6H); 3.06-3.35 (4H); 3.37-3.49 (1H); 3.51-3.73 (1H); 4.26-4.31 (0.1H); 4.45-4.52 (0.9H); 4.91-5.19 (1H); 6.97 (0.1H); 7.23 (0.9H). LC / MS (ESI+): 440.4 (calculated ([M + H] + ) : 440.3). AI4 molecule [000724] After a process similar to that used for the preparation of molecule A2 applied to molecule 31 (8.85 g, 20, 13 mmol) in solution in DCM, a white solid of molecule A14 is obtained after basic washing, concentration under reduced pressure and then recrystallization in acetonitrile. Yield: 6.53 g (96%) NMR 1 H (DMSO, ppm): 0.85 (3H); 1.07-1.56 (20H); 1.68-2.03 (4H); 2.09-2.29 (2H); 2.50-2.58 (2H); 2.96-3, 11 (2H); 3.21-3.59 (2H); 4.17-4.21 (0.65H); 4.25-4.29 (0.35H); 7.68 (0.65H); 8.00 (0.35H) LC / MS (ESI): 340.3; (calculated ([M + H] + ): 340.3). ,3). Molecule A15 [000725] Molecule A15 is obtained by the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (16.0 g, 1.16 mmol / g). [000726] The grafting of ethylenediamine (20.0 equivalents) is carried out in the DCM (10V). The sites that did not react are capped with methanol (0.8 mL / g resin) at the end of the reaction. [000727] Couplings of protected amino acids Fmoc-Lys(Fmoc)-OH (3.0 equivalents), Fmoc-Glu(OBn)-OH (4.0 equivalents) and molecule 11 (3.0 equivalents) are carried out in DMF (10V) (Lys couplings and molecule 11) or a DCM / DMF 1:1 mixture (10V) (Glu coupling), in the presence of HATU (1.0 equivalent with respect to the acid) and DIPEA (1.5 equivalents with respect to the acid). [000728] The Fmoc protecting groups are removed using a DMF / piperidine 80:20 (10 V) solution (after coupling of lysine) or a 1% DBU solution in DMF (after coupling of glutamic acids) [000729] The product is cleaved from the resin using a 50:50 DCM / TFA solution (10 V). After evaporation, the residue is solubilized in ethyl acetate (400 mL) and the organic phase is washed with an aqueous solution of buffer carbonate at pH 10 (1 M) (2 x 400 mL) followed by a saturated aqueous solution of NaCl (400 mL). After drying over Na₂SO₄, the organic phase is filtered, concentrated under reduced pressure, and the residue is purified by silica gel chromatography (dichloromethane, methanol, NFUOH), then by recrystallization in acetonitrile. Yield: 16.20 g (70% overall over 7 steps). NMR X H (DMSO-de, ppm): 0.85 (6H); 1.11-2.57 (72H); 2.50-5.57 (2H); 2.90-3.08 (4H); 3.36-3.61 (4H); 4.06-4.43 (5H); 5.08 (4H); 7.27-7.40 (10H); 7.51-8.31 (5H). LC / MS (ESI-F): 1242.0 (calculated ([M+H] + ): 1241.9). Example A16: Molecule A16 Molecule 32: Product obtained by SPPS [000730] Molecule 32 is obtained by the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (50.0 g, 1.14 mmol / g). [000731] The grafting of the first amino acid Fmoc-Glu(OtBu)-OH (1.3 equivalents) is carried out in DCM (10V), in the presence of DIPEA (2.6 equivalents). The unreacted sites are capped with methanol (0.8 mL / g resin) at the end of the reaction. [000732] The couplings of the protected amino acid Fmoc-Glu(OtBu)-OH (1.3 equivalents) and of molecule 11 (3.0 equivalents) are carried out in DMF (10V), in the presence of HATU (1.0 equivalent with respect to the acid) and DIPEA (1.5 equivalents with respect to the acid). [000733] ​​The Fmoc protecting groups are removed using a DMF / piperidine 80:20 (10 V) solution. [000734] The product is cleaved from the resin using a DCM / HFIP 80:20 solution (10 V). After concentration under reduced pressure, the residue is purified by trituration in diisopropyl ether. Yield: 35.78 g (90%) NMR C H (CDCh, ppm): 0.88 (3H); 1.19-1.35 (20H); 1.43 (9H); 1.44 (9H); 1.55-1.67 (2H); 1.90-2.46 (2 p.m.); 3.46-3.54 (1 H); 3.63-3.71 (1H); 4.33-4.40 (1H); 4.43-4.52 (2H); 7.35 (0.05H); 7.40 (0.05H); 7.63 (0.95H); 7.94 (0.95H). LC / MS (ESI+): 696.4 (calculated ([M+H] + ) : 696.5). Molecule 33: Product obtained by the reaction between molecule 32 and N-CBz ethylenediamine. [000735] By a process similar to that used for the preparation of molecule 7 and applied to molecule 32 (30.0 g, 43.11 mmol) and N-CBz ethylenediamine hydrochloride (CBzEDA₂HCl, 11.93 g, 51.73 mmol), and in the presence of DIPEA (15.0 mL, 86.22 mmol), a beige solid of molecule 33 is obtained. It is used without further purification. Yield: 37.6 g (100%) NMR X H (CDCh, ppm): 0.88 (3H); 1, 19-1.34 (20H); 1.42 (9H); 1.44 (9H); 1.52-2.54 (16H); 3.16-3.70 (6H); 4.08-4.15 (1H); 4.19-4.25 (1H); 4.43-4.53 (1H); 5.00 (1H); 5.08 (1 H); 6.56 (1H); 7.00 (1H); 7.24-7.37 (5H); 7.59 (1H); 8.41 (1H) . LC / MS (ESI+): 872.5 (calculated ([M+H] + ) : 872.6). Molecule A16 [000736] To a solution of molecule 33 (37.6 g, 43.11 mmol) in methanol (376 mL), Pd / A Oa (3.76 g) is added under an argon atmosphere. The mixture is placed under a hydrogen atmosphere (7 bar) and stirred at room temperature for 72 h. After filtering the catalyst through P4 sintered material and then through a 0.2 µm hydrophilic Omnipore PTFE membrane, the filtrate is evaporated under reduced pressure to give molecule A16 in the form of a sticky oil. Yield: 31.06 g (98%) NMR (CDCb, ppm): 0.88 (3H); 1.19-1.35 (20H); 1.43 (9H); 1.46 (9H); 1.56-1.67 (2H); 1.92-2.12 (6H); 2.24-2.54 (8H); 2.71 (2H); 2.90 (2H); 3.22-3.32 (1H); 3.42-3.51 (1H); 3.55-3.64 (1H); 3.73-3.81 (1H); 4, 13-4,21 (1H); 4.26-4.33 (1H); 4.39-4.48 (1H); 7, 10 (1H); 7.71 (1H); 8.45 (1H). LC / MS (ESI+): 738.5 (calculated ([M + H] + ): 738.5). Molecule A17 [000737] Molecule A17 is obtained by the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (64.66 g, 1.16 mmol / g). [000738] The ethylenediamine (10.0 equivalents) grafting is carried out in DCM (10V), in the presence of DIPEA (10.0 equivalents). The unreacted sites are capped with methanol (0.8 mL / g resin) at the end of the reaction. [000739] The couplings of the protected amino acid Fmoc-Glu(OMe)-OH (1.5 equivalents) and molecule 28 (1.5 equivalents) are carried out in a DCM / DMF 1:1 mixture (10V) for the coupling of glutamic acid or in DMF (10V) for the coupling of molecule 28, in the presence of HATU (1.0 equivalent with respect to the acid) and DIPEA (2.0 equivalents with respect to the acid). [000740] The Fmoc protecting groups are removed using a 50:50 DMF / morpholine solution (10 V). [000741] The product is cleaved from the resin using a 50:50 DCM / TFA (10 V) solution. After evaporation, the residue is solubilized in MeTHF (500 mL) and the organic phase is washed with a 5% aqueous solution of IMazCOa (3 x 250 mL). The aqueous phases are then extracted with MeTHF (1 x 150 mL). The combined organic phases are dried over Na₂SO₄ and filtered. A 1.25 M HCl in MeOH solution is added, and the mixture is concentrated under reduced pressure. The residue is purified by silica gel chromatography (dichloromethane, methanol) to give the hydrochloride salt of molecule A17 in the form of a light brown solid. Yield: 12.48 g (30% overall over 5 steps). NMR X H (DMSO-de, ppm): 0.76-0.90 (12H); 0.97-1.41 (13H); 1.45-1.55 (1H); 1.68-2.40 (UH); 2.77-2.92 (2H); 3.20-3.64 (4H); 3.57 (3H); 4.15-4.49 (2H); 7.90- 8.48 (5H). LC / MS (ESI+): 525.5 (calculated ([M+H]+ ) : 525.4). Example A18: Molecule A18 Molecule 34: Product obtained by hydrogenation of phytol. [000742] To a phytol solution (260.00 g, 878.78 mmol) in ethanol (1.25 L) under argon, Raney nickel 50% in water (30.75 g, 175.36 mmol) is added. The mixture is placed under 1 bar of hydrogen and then agitated for 8 days at room temperature. After filtration through a celite / silica / celite pad, rinsing with ethanol, a colorless oil of molecular weight 34 is obtained after concentration under reduced pressure. Yield: 261.40 g (quantity). ¹H NMR (CDCh, ppm): 0.84 (6H); 0.86 (6H); 0.89 (3H); 1.00-1.46 (22H); 1.46-1.68 (3H); 3.61-3.73 (2H). Molecule 35: Product obtained by oxidation of molecule 34. [000743] By a process similar to that used for the preparation of molecule 26 applied to molecule 34 (29.00 g, 97.13 mmol), a yellow oil of molecule 35 is obtained. Yield: 28.70 g (94%) NMR (CDCh, ppm): 0.84 (6H); 0.86 (6H); 0.97 (3H); 1.00-1.41 (20H); 1.52 (1H); 1.96 (1H); 2.14 (1H); 2.35 (1H); 11.31 (1H). LC / MS (ESI): 311.1 (calculated ([MH]): 311.3). Molecule 36: Product obtained by coupling between molecule 35 and methyl L-prolinate. [000744] By a process similar to that used for the preparation of molecule 27 applied to molecule 35 (18.00 g, 57.59 mmol) and to methyl L-prolinate hydrochloride (14.31 g, 86.39 mmol), a yellow oil of molecule 36 is obtained. Yield: 23.20 g (95%) *H NMR (DMSO-de, ppm): 0.78-0.89 (15H); 0.97-1.43 (20H); 1.43-1.56 (1H); 1.70-1.96 (4H); 1.96-2.32 (3H); 3.33-3.56 (2H); 3.59 (0.6H); 3.67 (2.4H); 4.27 (0.8H); 4.57 (0.2H). LC / MS (ESI): 424.4 (calculated ([M + H] + ) : 424.4) . Molecule 37: Product obtained by the saponification of molecule 36. [000745] By a process similar to that used for the preparation of molecule 28 applied to molecule 36 (21.05 g, 49.68 mmol), a yellow oil of molecule 37 is obtained. Yield: 20.40 g (99%) NMR X H (DMSO-de, ppm): 0.77-0.91 (15H); 0.97-1.43 (20H); 1.43-1.56 (1H); 1.67-1.96 (4H); 1.96-2.29 (3H); 3.26-3.56 (2H); 4.20 (0.8H); 4.41 (0.2H). LC / MS (ESI): 410.3 (calculated ([M+H] + ): 410.4). Molecule A18 [000746] Molecule A18 is obtained by the conventional solid-phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (26.72 g, 1.16 mmol / g). [000747] By a process similar to that used for the preparation of molecule A17 applied to 4,7,10-trioxa-l, 13-tridecanediamine (TOTA, 68.30 g, 310.0 mmol), to Fmoc-Glu(OMe)-OH (23.77 mmol, 62.00 mmol) and to molecule 37 (19.04 g, 46.50 mmol), a yellow oil of molecule A18 in the form of hydrochloride is obtained. Yield: 5.53 g (23% overall over 5 steps). NMR ^ (DMSO-de, ppm): 0.76-0.89 (15H); 0.97-2.38 (36H); 2.77-2.87 (2H); 3.00- 3.17 (3H); 3.32-3.54 (1 p.m.); 3.57 (3H); 4.09-4.18 (0.75H); 4.20-4.29 (1H); 4.39-4.47 (0.25H); 7.63-8.36 (5H). LC / MS (ESI+): 755.7 (calculated ([M + H] + ): 755.6). Example A19: Molecule A19 [000748] Molecule A19 is synthesized in the same way as molecule A16 using molecule 14 instead of molecule 11 in the SPPS step. Overall yield (3 stages): 32.6 g (81%) NMR (CDCh, ppm): 0.88 (3H); 1.20-1.35 (16H); 1.43 (9H); 1.46 (9H); 1.56-1.68 (2H); 1.93-2, 11 (6H); 2.24-2.55 (10H); 2.85 (2H); 3, 19-3.29 (1H); 3.38-3.48 (1H); 3.55-3.64 (1H); 3.74-3.82 (1 H); 4, 14-4,21 (1H); 4.25-4.32 (1H); 4.41-4.50 (1H); 7.03 (1H); 7.69 (1H); 8.42 (1H). LC / MS (ESI): 710.4 (calculated ([M + H] + ) : 710.5). Example A20: Molecule A20 [000749] The A20 molecule is obtained by the conventional solid phase peptide synthesis (SPPS) method on 2-chlorotrityl chloride (CTC) resin (40.00 g, 1.16 m mol / g). [000750] The ethylenediamine (20.0 equivalents) grafting is carried out in DCM (10V). The unreacted sites are capped with methanol (0.8 mL / g resin) at the end of the reaction. [000751] Couplings of protected amino acids Fmoc-Lys(Fmoc)-OH (1.5 equivalents), Fmoc-Glu(OtBu)-OH (2.5 equivalents) and molecule 11 (2.5 equivalents) are carried out in DMF (10 V), in the presence of HATU (1.0 equivalent with respect to the acid) and DIPEA (1.5 equivalents with respect to the acid). [000752] The Fmoc protecting groups are removed using a DMF / piperidine 80:20 (10 V) solution. [000753] The product is cleaved from the resin using a 50:50 DCM / TFA solution (10 V). After evaporation, the residue is dissolved in water (600 mL), the pH of the solution is adjusted to 7 by adding 5 N NaOH, and then the product is lyophilized. The lyophilized product is purified by silica gel chromatography (dichloromethane, methanol, NF-OH) to give the A20 molecule as a white solid. Yield: 24.6 g (50% overall over 7 steps). eOD-d4, ppm): 0.90 (6H); 1.18-2.45 (68H); 2.45-2.60 (2H); 3.05-3.11 -3.19 (1H); 3.23-3.33 (1H); 3.43-3.66 (4H); 3.82-3.94 (2H); 4.10-4.51 I+): 1061.9 (calculated ( [M + H] + ): 1061.8). Part B - Synthesis of hydrophobic co-polyamino acids i) Co-polyamino acids of formula XXXa, XXXb and XXXb', XXXb" Co-polyamino acid B1: sodium poly-L-glutamate modified at one end by the Al molecule and having a number-average molar mass (Mn) of 2800 g / mol [000754] In a flask previously dried in an oven, g-benzyl-L-glutamate V-carboxyanhydride (8.95 g, 34 mmol) is dissolved in anhydrous DMF (34 mL). The mixture is cooled to 4 °C, and then a solution of Al₂O₅ (1.64 g, 1.55 mmol) in chloroform (6.6 mL) is rapidly added. The mixture is stirred between 4 °C and room temperature for 68 h, and then heated to 65 °C for 2 h. Half of the solvent is distilled under reduced pressure, and the reaction mixture is cooled to room temperature and added dropwise to diisopropyl ether (300 mL) with stirring. The white precipitate is collected by filtration, washed with diisopropyl ether (5 x 50 mL), and then dried under reduced pressure at 30 °C to obtain a white solid. The solid (7.9 g) is diluted in TFA (30 mL), and a 33% hydrobromic acid (H Br) solution in acetic acid (21 mL, 120 mmol) is then added dropwise at 0 °C.The solution is stirred for 2 h at room temperature and then dripped onto a 1:1 (v / v) diisopropyl ether / water mixture (360 mL) while stirring. After 2 h of stirring, the heterogeneous mixture is left to stand overnight. The white precipitate is collected by filtration and washed successively with GIRE (2 x 30 mL) and then with water (2 x 30 mL). The resulting solid is dissolved in water (200 mL), adjusting the pH to 7 by adding a 1 N aqueous sodium hydroxide solution. Water (65 mL) is added. The mixture is filtered through a 0.45 µm filter and then purified by ultrafiltration against 0.9% NaCl solution and then water until the permeate conductivity is less than 50 pS / cm. The co-polyamino acid solution is then concentrated to approximately 25 g / L theoretical, the pH is adjusted to 7 and the aqueous solution is filtered through 0.2 pm.This solution is diluted with water and acetone to obtain a 12 g / L solution containing 30 wt% acetone, and then filtered through activated carbon (3M R53SLP). The acetone is distilled (40 °C, 100 mbar), and the solution is purified by ultrafiltration through 0.9% NaCl and then water until the permeate conductivity is less than 50 pS / cm. The co-polyamino acid solution is then concentrated, and the pH is adjusted to 7. The aqueous solution is filtered through 0.2 µm and stored at 4 °C. Dry extract: 17.8 mg / g DP (estimated from NMR) 1 H): 26 According to the *H NMR: i = 0.038 The calculated average molar mass of co-polyamino acid B1 is 4994 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 2800 g / mol. Co-polyamino acid B2: sodium poly-L-glutamate modified by molecule A2, whose esters are saponified, and having a number-average molar mass (Mn) of 5200 g / mol. Co-polyvaminoadde B2-1: poly-L-glutamic acid resulting from the polymerization of γ-benzyl-L-glutamate / V-carboxyanhydride initiated by hexylamine [000755] In a double-jacketed reactor, γ-benzyl-L-glutamate N-carboxyanhydride (500 g, 1.90 mol) is dissolved in anhydrous DMF (1100 mL). The mixture is then stirred until completely dissolved, cooled to 0 °C, and then hexylamine (6.27 mL, 47.5 mmol) is rapidly added. The mixture is stirred at 0 °C for 5 h, between 0 °C and 20 °C for 7 h, and then at 20 °C for 7 h. The reaction mixture is then heated to 65 °C for 2 h, cooled to 55 °C, and methanol (3300 mL) is added over 1.5 h. The reaction mixture is then cooled to 0 °C and stirred for 18 h. The white precipitate is recovered by filtration, washed with diisopropyl ether (2 x 800 mL) and then dried under reduced pressure at 30 °C to give poly(gamma-benzyl-L-glutamic) acid (PBLG). [000756] To a solution of PBLG (180 g) in / V, / V-dimethylacetamide (DMAc, 450 mL), Pd / A Ch (36 g) is added under an argon atmosphere. The mixture is placed under a hydrogen atmosphere (10 bar) and stirred at 60 °C for 24 h. After cooling to room temperature and filtration of the catalyst through P4 sintered glass and then through a hydrophilic Omnipore 0.2 µm PTFE membrane, a pH 2 water solution (2700 mL) is added dropwise to the DMAc solution over a period of 45 min with stirring. After 18 h with stirring, the white precipitate is recovered by filtration, washed with water (4 x 225 mL), and then dried under reduced pressure at 30 °C. Co-poiyaminoacid B2 [000757] Co-polyamino acid B2-1 (15.0 g) is solubilized in DMF (230 mL) at 40 °C, then / V-methylmorpholine (NMM, 11.57 g, 114.4 mmol) is added. In parallel, molecule A2 in the form of its hydrochloride salt (10.17 g, 17.2 mmol) is suspended in DMF (250 mL), and triethylamine (2.39 mL, 17.2 mmol) is added. The mixture is then gently heated with stirring until completely dissolved. To the co-polyamino acid solution, cooled to 25 °C, are The solution of molecule A2, 2-hydroxypyridine N-oxide (HOPO, 3.81 g, 34.3 mmol), and then EDC (6.58 g, 34.3 mmol) were successively added. The reaction mixture was stirred at 25 °C for 2 h, filtered through a 0.2 mm woven filter, and added dropwise to 2.6 L of water containing 15 wt% NaCl and HCl (pH 2) while stirring. At the end of the addition, the pH was readjusted to 2 with a 1% HCl solution. N, and the suspension is left to stand overnight. The precipitate is collected by filtration and then rinsed with 2 x 100 mL of water. The resulting white solid is solubilized in 1.2 L of water by slowly adding a 1 N aqueous NaOH solution until pH 7 is reached with stirring, and then the solution is filtered through a 0.45 µm filter. Ethanol (30 wt%) is added, and the solution is filtered through a 3 M R53SLP activated carbon filter. A 10 N NaOH solution is slowly added with stirring until pH 13 is reached, and the mixture is left to stir for 2 h. After neutralization to pH 7 by adding a 37% HCl solution, the clear solution obtained is purified by ultrafiltration against a 0.9% NaCl solution and then water, until the permeate conductivity is less than 50 pS / cm. The co-polyamino acid solution is then concentrated and the pH is adjusted to 7. The aqueous solution is filtered through 0.2 µm and stored at 4 °C. Dry extract: 22.6 mg / g DP (estimated) According to the *H NMR: i = 0.15 The calculated average molar mass of co-polyamino acid B2 is 9301 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 5200 g / mol. Co-polyamino acid B3: sodium poly-L-glutamate modified by molecule A3, whose ester is saponified, and having a number-average molar mass (Mn) of 4900 g / mol [000758] Co-polyamino acid B2-1 (12.0 g) is solubilized in DMF (92 mL) at 40 °C, and then β-V-methylmorpholine (NMM, 9.25 g, 91.5 mmol) is added. In parallel, a solution of molecule A3 as its hydrochloride salt (7.51 g, 13.7 mmol) and β-V,β-diisopropylethylamine (DIPEA, 2.39 mL, 13.7 mmol) in DMF (27 mL) is prepared. The solution of molecule A3 and 2-hydroxypyridine N-oxide (HOPO, 3.05 g, 27.4 mmol) are successively added to the co-polyamino acid solution cooled to 25 °C. The mixture is cooled to 0 °C, then EDC (5.26 g, 27.4 mmol) is added. After 5 min at 0 °C, the reaction mixture is stirred at 25 °C for 2 h, filtered through a 0.2 mm woven filter, and dripped onto 950 mL of water containing 15 wt% NaCl and HCl (pH 2) while stirring. At the end After the addition, the pH is readjusted to 2 with a 1 N HCl solution, and the suspension is left to stand overnight. The precipitate is collected by filtration and then rinsed with 3 x 100 mL of water. The resulting solid is solubilized in 1 L of water by slowly adding a 1 N aqueous NaOH solution until pH 7 is reached with stirring. Once solubilization is complete, the pH is adjusted to 12 for 2 h and then to 13 for 1 h by adding a 10 N NaOH solution. After neutralization to pH 7 by adding a 37% HCl solution, this solution is diluted with water and ethanol to obtain a 12 g / L solution containing 30 wt% ethanol, and then filtered through a 3M R53SLP activated carbon filter. The resulting solution is filtered through 0.45 µm and purified by ultrafiltration against a 0.9% NaCl solution and then water until the permeate conductivity is less than 50 pS / cm. The co-polyamino acid solution is then concentrated and the pH is adjusted to 7.The aqueous solution is filtered through 0.2 µm and stored at 4 °C. Dry extract: 20.6 mg / g DP (estimated from NMR) a H): 40 According to the RMN 1 H: i = 0.15 The calculated average molar mass of co-polyamino acid B3 is 8977 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 4900 g / mol. Co-polyamino acid B4: sodium poly-L-glutamate modified by molecule A4, whose ester is saponified, and having a number-average molar mass (Mn) of 4700 g / mol. [000759] By a process similar to that used for the preparation of co-polyamino acid B3 applied to the hydrochloride salt of molecule A4 (7.12 g, 13.7 mmol) and to co-polyamino acid B2-1 (12.0 g), a poly-L-glutamate of sodium modified by molecule A4 whose ester is saponified is obtained. Dry extract: 19.4 mg / g DP (estimated from H NMR): 40 According to the *H NMR: i = 0.15 The calculated average molar mass of co-polyamino acid B4 is 8809 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 4700 g / mol. Co-polyamino acid B5: sodium poly-L-glutamate modified by the AS molecule, whose ester is saponified, and having a number-average molar mass (Mn) of 5400 g / mol [000760] By a process similar to that used for the preparation of co-polyamino acid B3 applied to the hydrochloride salt of molecule A5 (9.71 g, 13.7 mmol) and to co-polyamino acid B2-1 (12.0 g), a poly-L-glutamate of sodium modified by molecule A5 whose ester is saponified is obtained. Dry extract: 20.8 mg / g DP (estimated from NMR) 1 H): 40 According to the RMN 1 H: i = 0.15 The calculated average molar mass of co-polyamino acid B5 is 9939 g / mol. Organic HPLC-SEC (PEG calibrator): n = 5400 g / mol. Co-polyamino acid B7: sodium poly-L-glutamate modified at one end by molecule A7 and having a number-average molar mass (Mn) of 2500 g / mol [000761] By a process similar to that used for the preparation of co-polyaminoacid B1 applied to molecule A7 (2.50 g, 2.74 mmol) and to y-benzyl-L-glutamate / V-carboxyanhydride (15.89 g, 60.4 mmol), a sodium poly-L-glutamate modified at one of its ends by molecule A7 is obtained. Dry extract: 20.3 mg / g DP (estimated from MN) C H): 26 According to RM 0.038 The calculated average molar mass of co-polyamino acid B7 is 3893 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 2500 g / mol Co-polyamino acid B13: sodium poly-L-glutamate modified at one end by the garlic molecule, whose esters are deprotected, and having a number molar mass (Mn) of 3000 g / mol [000762] In a double-jacketed reactor, g-benzyl-L-glutamate N-carboxyanhydride (24.50 g, 93.05 mmol) is solubilized in anhydrous DMF (55 mL). The mixture is then stirred until completely dissolved, cooled to 0 °C, and then hexylamine (0.56 mL, 4.23 mmol) is rapidly introduced. The mixture is stirred at 0 °C for 48 h, and then a solution of Al₂I₂ (9.51 g, 5.08 mmol) in DMF (50 mL), HOPO (564 mg, 5.08 mmol), and EDC (973 mg, 5.08 mmol). The reaction mixture is stirred at 0 °C for 1 h, between 0 °C and 20 °C for 2 h, and then at 20 °C for 16 h. This solution is then poured into a 1:1 (10 V) FhO / MeOH mixture at room temperature with stirring. After 4 h with stirring, the white precipitate is recovered by filtration, washed with diisopropyl ether (2 x 100 mL), water (2 x 100 mL), and a 1:1 FhO / MeOH mixture (2 x 100 mL), and then dried under reduced pressure. [000763] The resulting solid is dissolved in TFA (220 mL) and stirred at room temperature for 2.5 hours. This solution is then poured into water (10 V) at room temperature while stirring. After 2.5 hours of stirring, the white precipitate is recovered by filtration, washed with water (2 x 200 mL), and then dried under reduced pressure. [000764] The resulting solid is solubilized in L / , / V-dimethylacetamide (DMAc, 210 mL), and then Pd / AteCb (2.1 g) is added under an argon atmosphere. The mixture is placed under a hydrogen atmosphere (6 bar) and stirred at 60 °C for 24 h. After cooling to room temperature and filtering the catalyst through P4 sintered glass and then through a 0.2 µm hydrophilic Omnipore PTFE membrane, a pH 2 water solution containing 15% NaCl (6 V) is added dropwise to the DMAc solution over a period of 45 min with stirring. After 18 h with stirring, the white precipitate is recovered by filtration, washed with water, and then dried under reduced pressure. The solid obtained is solubilized in water (600 mL) by adjusting the pH to 7 by adding a 1 N aqueous sodium hydroxide solution. The pH is then adjusted to pH 12 and the solution is kept under stirring for 1 h.After neutralization to pH 7, the solution is filtered through a 0.2 µm filter, diluted with ethanol to obtain a 30 wt% ethanol solution, and then filtered through activated carbon (3M R53SLP). The resulting solution is filtered through a 0.45 µm filter and purified by ultrafiltration against a 0.9% NaCl solution and then water until the permeate conductivity is less than 50 pS / cm. The co-polyamino acid solution is then concentrated and the pH adjusted to 7. The aqueous solution is filtered through a 0.2 µm filter and stored at 4 °C. Dry extract: 23.5 mg / g DP (estimated by NMR) 1 H) = 24 therefore i = 0.042 The calculated average molar mass of co-polyamino acid B13 is 5377 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 3000 g / mol. Co-polyamino acid B14: sodium poly-L-glutamate modified at one end by the A12 molecule, whose esters are deprotected, and having a number molar mass (Mn) of 3300 g / mol Co-poivaminoacid B14 - 1: poly-L-benzylglutamate modified at one end by the A12 molecule. [000765] In a previously oven-dried flask, γ-benzyl-L-glutamate / V-carboxyanhydride (50.00 g, 189.39 mmol) is dissolved in anhydrous DMF (65 mL). The mixture is then stirred until completely dissolved, cooled to 0 °C, and then a solution of molecule A12 (9.65 g, 8.63 mmol) in DMF (50 mL) is rapidly introduced. The mixture is stirred between 0 °C and room temperature for 2 days, then heated to 65 °C for 2 h. The reaction mixture is then cooled to room temperature and added dropwise to diisopropyl ether (1.8 L) while stirring. The white precipitate is collected by filtration, washed twice with diisopropyl ether, and then dried under vacuum at 30 °C to obtain a white solid. Co-polyamino acid B14 [000766] Co-polyamino acid B14-1 is solubilized in DMAc (250 mL), and then Pd / Al₂O₃ (5.0 g) is added under an argon atmosphere. The mixture is placed under a hydrogen atmosphere (10 bar) and stirred at 60 °C for 24 h. After cooling to room temperature and filtering the catalyst through P4 sintered material and then through a 0.2 µm hydrophilic Omnipore PTFE membrane, a pH 2 (6 V) water solution is added dropwise to the DMAc solution over a period of 45 min with stirring. After 18 h with stirring, the white precipitate is recovered by filtration, washed with water, and then dried under reduced pressure. The resulting solid is solubilized in water (1.25 L), adjusting the pH to 7 by adding a 1 IM aqueous sodium hydroxide solution. The pH is then adjusted to pH 13 and the solution is kept under stirring for 3 hours.After neutralization to pH 7, the solution is filtered through a 0.2 µm filter, diluted with ethanol to obtain a 30 wt% ethanol solution, and then filtered through activated carbon (3M R53SLP). The resulting solution is filtered through a 0.45 µm filter and purified by ultrafiltration against a 0.9% NaCl solution and then water until the permeate conductivity is less than 50 pS / cm. The co-polyamino acid solution is then concentrated and the pH adjusted to 7. The aqueous solution is filtered through a 0.2 µm filter and stored at 4 °C. Dry extract: 25.7 mg / g DP (estimated by RM N ^) = 24 therefore i = 0.042 The calculated average molar mass of co-polyamino acid B14 is 4720 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 3300 g / mol. Co-polyamino acid B15: sodium poly-L-glutamate modified by molecule A13, whose esters are deprotected, and having a number molar mass (Mn) of 4400 g / mol [000767] By a process similar to that used for the preparation of co-polyamino acid B3 applied to the hydrochloride salt of molecule A13 (3.39 g, 2.34 mmol) and to co-polyamino acid B2-1 (2.04 g), with a saponification step at pH 13 for 5 h in a mixture of water containing 30 wt% ethanol, a poly-L-sodium glutamate modified by molecule A13 whose esters are deprotected is obtained. Dry extract: 15.7 mg / g DP (estimated from HM NMR): 40 According to the *H NMR: i = 0.15 The calculated average molar mass of co-polyamino acid B15 is 12207 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 4400 g / mol. Co-polyamino acid B17: sodium poly-L-glutamate modified at one end by the A15 molecule, whose esters are deprotected, and having a number-average molar mass (Mn) of 1000 g / mol [000768] By a process similar to that used for the preparation of co-polyamino acid B14 applied to molecule A15 (10.85 g, 8.74 mmol) and to γ-benzyl-L-glutamate / V-carboxyanhydride (23.00 g, 87.37 mmol), with a saponification step at pH 12 for 2 h, a sodium poly-L-glutamate modified at one of its ends by molecule A15 whose esters are deprotected is obtained. Dry extract: 23.9 mg / g DP (estimated from *H NMR): 10 According to the *H NMR: i = 0.1 The calculated average molar mass of co-polyamino acid B17 is 2576 g / mol. Aqueous HPLC-SEC (PEG calibrator): Mn = 1000 g / mol. Co-polyamino acid B18: sodium poly-L-glutamate modified by molecule A16, whose esters are deprotected and having a number molar mass (Mn) of 5000 g / mol [000769] By a coupling process similar to that used for the preparation of co-polyamino acid B3 applied to molecule A16 (31.06 g, 42.08 mmol) and co-polyamino acid B2-1 (36.80 g), a beige solid is obtained after the acid precipitation step. This solid is diluted in TFA (100 g / L) and the mixture is stirred at room temperature for 3 h. The solution is then dripped onto water (3 V) while stirring. After 16 h of stirring, the precipitate is recovered by filtration and then washed with water. The solid obtained is solubilized in water by adjusting the pH to 7 by adding a 10 N aqueous sodium hydroxide solution. Once solubilization is complete, the pH is adjusted to pH 12 for 1 h by adding a 1 N NaOH solution. After neutralization to pH 7 by adding a 1 N HCl solution, the product is purified by a process similar to that used for the preparation of co-polyamino acid B3 (carbofiltration and ultrafiltration).A poly-L-sodium glutamate modified by the A16 molecule, whose esters are deprotected, is obtained. Dry extract: 28.2 mg / g DP (estimated from NMR) X H): 40 According to the RMN 1 H: i = 0.15 The calculated average molar mass of co-polyamino acid B18 is 9884 g / mol. Organic HPLC-SEC (PEG calibrator): n = 5000 g / mol. Co-polyamino acid B19: sodium poly-L-glutamate modified by molecule A17, whose esters are deprotected, and having a number molar mass (Mn) of 4900 g / mol [000770] By a process similar to that used for the preparation of co-polyamino acid B3 applied to the hydrochloride salt of molecule A17 (7.35 g, 13.09 mmol) and to co-polyamino acid B2-1 (11.45 g), with a saponification step at pH 13 for 3 h in a mixture of water containing 30 wt% ethanol, a poly-L-sodium glutamate modified by molecule A17 whose esters are deprotected is obtained. Dry extract: 25.7 mg / g DP (estimated from the NMR) X H): 40 According to the *H NMR: i = 0.15 The calculated average molar mass of co-polyamino acid B19 is 9062 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 4900 g / mol. Co-polyamino acid B20: sodium poly-L-glutamate modified by molecule A18, whose esters are deprotected and having a number molar mass (Mn) of 5800 g / mol [000771] By a process similar to that used for the preparation of co-polyamino acid B3 applied to the hydrochloride salt of molecule A18 (5.43 g, 6.86 mmol) and to co-polyamino acid B2-1 (6.00 g), with a saponification step at pH 13 for 3 h in a mixture of water containing 30 wt% ethanol, a poly-L-sodium glutamate modified by molecule A18 whose esters are deprotected is obtained. Dry extract: 22.0 mg / g DP (estimated from NMR) 1 H): 40 According to the *H NMR: i = 0.15 The calculated average molar mass of co-polyamino acid B20 is 10444 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 5800 g / mol. Co-polyamino acid B21: sodium poly-L-glutamate modified by molecule A19, whose esters are deprotected and having a number molar mass (Mn) of 5000 g / mol [000772] By a process similar to that used for the preparation of co-polyamino acid B18 applied to molecule A19 (32.64 g, 45.97 mmol) and to co-polyamino acid B2-1 (40.20 g), a poly-L-glutamate of sodium modified by molecule A19 whose esters are deprotected is obtained. Dry extract: 26.2 mg / g DP (estimated from NMR) a H): 40 According to the MH NMR: i = 0.15 The calculated average molar mass of co-polyamino acid B21 is 9716 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 5000 g / mol. Co-polyamino acid B22: sodium poly-L-glutamate modified at one end by molecule A20 and having a number-average molar mass (Mn) of 1900 g / mol [000773] By a process similar to that used for the preparation of co-polyamino acid B14 applied to molecule A20 (13.28 g, 12.51 mmol) in CHC (53 mL) and to g-benzyl-L-glutamate / V-carboxyanhydride (72.46 g, 275.2 mmol) in DMF (270 mL), with a saponification step at pH 12 for 1 h 30, a sodium poly-L-glutamate modified at one of its ends by molecule A20 is obtained. Dry extract: 27.3 mg / g DP (estimated from NMR) C H): 20 According to the *H NMR: i = 0.05 The calculated average molar mass of co-polyamino acid B22 is 4087 g / mol. Aqueous HPLC-SEC (PEG calibrator): Mn = 1900 g / mol. Co-polyamino acids of formulas XXXa, XXXb, XXXb' and XXXb REPLACEMENT SHEET (RULE 26) REPLACEMENT SHEET (RULE 26) Co-polyamino acid B7': sodium poly-L-glutamate modified at one end by the A5a molecule and having a number-average molar mass (Mn) of 2600 g / mol Cprpolya m in pactde B7'- l : poly-L-benzylgluta ate modified at one of its ends by the A5a molecule. [000774] In a previously oven-dried flask, γ-benzyl-L-glutamate / V-carboxyanhydride (10.1 g, 38.4 mmol) is dissolved in anhydrous DMF (19 mL). The mixture is then stirred until completely dissolved, cooled to 0 °C, and then a solution of molecule A5a (1.47 g, 1.74 mmol) in chloroform (3.7 mL) is rapidly introduced. The mixture is stirred between 0 °C and room temperature for 2 days, then heated to 65 °C for 2 h. The reaction mixture is then cooled to room temperature and added dropwise to diisopropyl ether (0.29 L) while stirring. The white precipitate is collected by filtration, washed twice with diisopropyl ether (5 x 50 mL), and then dried under vacuum at 30 °C to obtain a white solid. REPLACEMENT SHEET (RULE 26) Co-polyamino acid B7' [000775] Co-polyamino acid B7'-l (8.33 g, 33.0 mmol) is diluted in trifuloroacetic acid (TFA, 132 mL), and the solution is cooled to 4 °C. A 33% HBr solution in acetic acid (92.5 mL, 0.528 mol) is then added dropwise. The mixture is stirred at room temperature for 2 h, and then dripped onto a 1:1 (v / v) mixture of diisopropyl ether and water (0.8 L) while stirring. After 2 h of stirring, the heterogeneous mixture is left to stand overnight. The white precipitate is recovered by filtration, washed with IPE (2 x 66 mL), and then with water (2 x 66 mL). The resulting solid is then solubilized in water (690 mL) by adjusting the pH to 7 by adding a 1 N aqueous sodium hydroxide solution.After solubilization, the theoretical concentration is adjusted to 20 g / L by adding water (310 mL). The solution is filtered through a 0.45 µm filter and then purified by ultrafiltration against a 0.9% NaCl solution, followed by water until the permeate conductivity is less than 50 pS / cm. The resulting solution is filtered through a 0.2 µm filter and stored at 2–8 °C. Dry extract: 17.3 mg / g DP (estimated at M 1 H): 24 According to RM 0.042 The calculated average molar mass of co-polyamino acid B7' is 4430 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 2600 g / mol. Example BS: co-polyamino acid B8 - sodium poly-L-glutamate modified at one end by molecule A6a and having a number-average molar mass (Mn) of 2400 g / mol Co-polyamino acid B8-1: poly-L-benzylglutamate modified at one end by the A6 molecule. [000776] In a flask previously dried in an oven, γ-benzyl-L-glutamate / V-carboxyanhydride (19.0 g, 72.2 mmol) is dissolved in anhydrous DMF (19 mL). The mixture is then stirred until completely dissolved, cooled to 0 °C, and then a solution of molecule A6a (1.68 g, 3.28 mmol) in chloroform (3.7 mL) is rapidly introduced. The mixture is stirred between 0 °C and room temperature for 2 days, then heated to 65 °C for 2 h. The reaction mixture is then cooled to room temperature and added dropwise to diisopropyl ether (0.29 L) while stirring. The white precipitate is collected by filtration and washed twice. with diisopropylether (5 x 50 mL) then dried under vacuum at 30 °C to obtain a white solid. Co-polyamino acid B8 [000777] By a process similar to that used for the preparation of co-polyaminoacid B7' applied to co-polyaminoacid B8-1 (14.6 g, 61.5 mmol), a sodium poly-L-glutamate modified at one of its ends by the A6a molecule is obtained. Dry extract: 21.3 mg / g DP (estimated from NMR) 23 According to the RMN 1 H: i = 0.043 The calculated average molar mass of co-polyamino acid B8 is 3948 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 2400 g / mol. BIO co-polyamino acid: sodium poly-L-glutamate modified at one end by the A8 molecule and having a number-average molar mass (Mn) of 3100 g / mol Co-poivaminoacid B10-1: poly-L-benzylglutamate modified at one end by the A8 molecule. [000778] In a suitable container, the hydrochloride salt of molecule A8 (2.308 g, 3.04 mmol), chloroform (120 mL), 4 Å molecular sieve (1.5 g), and Amberlite IRN 150 ion-exchange resin (1.5 g) are introduced successively. After 1 h of roller agitation, the mixture is filtered and the resin is rinsed with chloroform. The mixture is evaporated and then co-evaporated with toluene. The residue is dissolved in anhydrous DMF (40 mL) for direct use in the polymerization reaction. [000779] In a previously oven-dried flask, γ-benzyl-L-glutamate / V-carboxyanhydride (20.0 g, 76.0 mmol) is dissolved in anhydrous DMF (19 mL). The mixture is then stirred until completely dissolved, cooled to 0 °C, and then a previously prepared solution of molecule A8 in chloroform (3.7 mL) is rapidly introduced. The mixture is stirred between 0 °C and room temperature for 2 days, then heated to 65 °C for 2 h. The reaction mixture is then cooled to room temperature and added dropwise to diisopropyl ether (0.29 L) while stirring. The white precipitate is collected by filtration and washed twice. with diisopropylether (5 x 50 mL) then dried under vacuum at 30 °C to obtain a white solid. Co-polyamino acid B10 [000780] By a process similar to that used for the preparation of co-polyaminoacid B7' applied to co-polyaminoacid B10-1 (15.2 g, 60.8 mmol), a sodium poly-L-glutamate modified at one of its ends by molecule A8 is obtained. Dry extract: 34.1 mg / g DP (estimated from NMR) : 31 According to R^: i = 0.032 The calculated average molar mass of co-polyamino acid B10 is 5367 g / mol. Organic HPLC-SEC (PEG calibrator): n = 3100 g / mol. Example Bll: co-polyamino acid Bl l - sodium poly-L-glutamate modified at one end by molecule A9 and having a number-average molar mass (Mn) of 3000 g / mol Co-polvaminoackle Bl l - 1 : poly-L-benzylglutamate modified at one of its ends by the A9 molecule. [000781] In a suitable container, the hydrochloride salt of molecule A9 (2.023 g, 3.87 mmol), chloroform (120 mL), 4 Å molecular sieve (1.5 g), and Amberlite IRN 150 ion-exchange resin (1.5 g) are introduced successively. After 1 h of roller agitation, the mixture is filtered and the resin is rinsed with chloroform. The mixture is evaporated and then co-evaporated with toluene. The residue is dissolved in anhydrous DMF (40 mL) for direct use in the polymerization reaction. [000782] By a process similar to that used for the preparation of co-polyamino acid B8-1 applied to the solution of molecule A9 previously prepared and to g-benzyl-L-glutamate / V-carboxyanhydride (25.5 g, 96.8 mmol), co-polyamino acid Bl l-1 is obtained. Co-polyamino acid Bl l [000783] By a process similar to that used for the preparation of co-polyamino acid B7' applied to co-polyamino acid Bl l-1 (18.4 g, 77.3 mmol), a poly-L-glutamate of sodium modified at one of its ends by the A9 molecule is obtained. Dry extract: 28.0 mg / g DP (estimated from NMR) X H): 29 According to the RN C H: i = 0.034 The calculated average molar mass of the co-polyamino acid Bll is 4828 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 3000 g / mol. Co-polyamino acid B12: sodium poly-L-glutamate modified at one end by the AlO₂ molecule and having a number-average molar mass (Mn) of 2700 g / mol Co-polyaminoacid B12-1: poly-L-benzylglutamate modified at one end by the A10 molecule. [000784] By a process similar to that used for the preparation of co-polyamino acid B10-1 applied to molecule A10 (3.0 g, 2.24 mmol) and to y-benzyl-L-glutamate / V-carboxyanhydride (12.99 g, 49.3 mmol), co-polyamino acid B12-1 is obtained. Co-polyamino acid B12 [000785] By a process similar to that used for the preparation of co-polyaminoacid B7' applied to co-polyaminoacid B12-1 (13.2 g, 48.0 mmol), a sodium poly-L-glutamate modified at one of its ends by the A10 molecule is obtained. Dry extract: 13.2 mg / g DP (estimated from MN ^): 24 According to RM 0.042 The calculated average molar mass of co-polyamino acid B12 is 4924 g / mol. Organic HPLC-SEC (PEG calibrator): Mn = 2700 g / mol. Part EC - Co-poivaminoacids counterexample s REPLACEMENT SHEET (RULE 26) [000786] The co-polyamino acids CEI and CE2 are synthesized according to the process described in application WO2017211916. Part C - Compositions Example Cl; ^lMlm^jtlosAjllae rapid aoalogiig iHunialog":! at 100 U / ffli [000787] This solution is a commercial lispro insulin solution marketed by the company ELI LILLY under the name Humalog ® This product is a rapid-acting insulin analog. The excipients in Humalog ® are meta-cresol (3.15 mg / mL), glycerol (16 mg / mL), disodium phosphate (1.88 mg / mL), zinc oxide (to have 0.0197 mg of zinc ion / mL), sodium hydroxide and hydrochloric acid for adjusting the pH (pH 7-7.8) and water. REPLACEMENT SHEET (RULE 26) Example C2. ; Rapid-acting insulin analog solution lispca_à_lflfl SQQ U / mL [000788] This solution is an insulin solution prepared from lispro insulin powder produced by Gan & Lee. This product is a rapid-acting insulin analog. The excipients used are m-cresol, glycerol, zinc oxide, sodium hydroxide, and hydrochloric acid for pH adjustment (pH 7-7.8), and water. The zinc concentration is 300 mM per 100 IU / mL of insulin. The concentration of the other excipients varies depending on the lispro concentration to obtain the desired concentrations in the final formulations. Example C3; Long-acting insulin analog solution . 1QP U / mL [000789] This solution is a commercial insulin glargine solution marketed by the company SANOFI under the name Lantus ® This product is a long-acting insulin analogue. The excipients in Lantus ®are zinc chloride (30 pg / mL), m-cresol (2.7 mg / mL), glycerol (20 mg / mL), polysorbate 20 (16 pM), sodium hydroxide and hydrochloric acid for pH adjustment (pH 4) and water. Example C4 Insulin solution qlarqine_i_100-40Q [000790] This solution is an insulin glargine solution prepared from insulin glargine powder produced by Gan8iLee. This product is a long-acting insulin analog. The excipients used are zinc chloride, m-cresol, glycerol, sodium hydroxide, and hydrochloric acid for pH adjustment (pH 4), and water. The zinc concentration is 460 pM per 100 IU / mL of insulin. The concentration of the other excipients varies depending on the concentration of glargine to obtain the desired concentrations in the final formulations. Part CA - Compositions containing insulin glargine G0007911 CAI preparation process: Preparation of a diluted co-polyamino acid / insulin glargine 50 U / mL composition at pH 7.1, following a process using insulin glargine in liquid form (in solution) and a co-polyamino acid in liquid form (in solution). [000792] To a co-polyamino acid stock solution at pH 7, concentrated solutions of metacresol and glycerin are added to obtain a co-polyamino acid solution with a concentration of Cstock co-polyamino acid / extracts (mg / mL). The amount The added excipients are adjusted to obtain a meta-cresol concentration of 35 mM and glycerin of 184 mM in the co-polyamino acid / insulin glargine 50 U / mL composition at pH 7.1. [000793] In a sterile container, a volume Vm of an insulin glargine solution at a concentration of 100 U / mL described in C3 or C4 is added to a volume Vmother of a co-polyamino acid solution at the concentration Cmother of a co-polyamino acid solution at the concentration Cmother of a co-polyamino acid solution at the concentration Cmother of a co-polyamino acid solution at the concentration Cmother of a co-polyamino acid solution at the concentration Cmother of a co-polyamino acid solution at the concentration Cmother of a co-polyamino acid solution at the concentration Cmother of a co-polyamino acid solution at the concentration Cco-polyamino acid at pH 7.1 to obtain a diluted composition Cco-polyamino acid (mg / mL) / insulin glargine 50 U / mL at pH 7.1. A cloudiness appears. The pH is adjusted to pH 7.1 by adding concentrated NaOH and the solution is placed at 40 °C for 2 h until completely solubilized. This visually clear solution is then placed at 4 °C. CA2 preparation process; Preparation of a co-polyamino acid / insulin glargine composition concentrated at pH 7.1 using a co-polyamino acid, following a process for concentrating a dilute composition. [000794] A co-polyamino acid / insulin glargine 50 U / mL composition at pH 7.1 described in Example CAI is concentrated by ultrafiltration through a 3 kDa regenerated cellulose membrane (Amicon ®Ultra-15 (marketed by Millipore). Following this ultrafiltration step, the retentate is clear, and the insulin glargine concentration is determined by reversed-phase chromatography (RP-HPLC). The insulin glargine concentration is then adjusted to the desired value by dilution in a solution of m-cresol / glycerin / Tween 20 excipients to obtain a final m-cresol concentration of 35 mM, a Tween 20 concentration of 52 mM, and an osmolarity of 300 mOsm / kg. The pH is measured and adjusted to pH 7.1 by adding concentrated NaOH and HCl. This visually clear solution at pH 7.1 has an insulin glargine concentration Csu glargine (U / mL) and a co-polyamino acid concentration Cco-polyamino acid (mg / mL) = Csu- diluted polyamino acid (mg / mL) X Csu glargine (U / mL) / 50 (U / mL).CA3 preparation process: Preparation of a concentrated co-polyamino acid / insulin glargine composition at pH 7.1, following a process using insulin glargine in liquid form (in solution) and a co-polyamino acid in liquid form (in solution). [000795] A glargine solution at 220-400 IU / mL containing the excipients described in Example C4 is added to a stock solution of a co-polyamino acid at pH 7.1. The concentration of excipients in the glargine solution is adjusted to obtain a m-cresol concentration of 35 mM and a glycerin concentration of 184 mM in the co-polyamino acid / insulin glargine composition at pH 7.1. A cloudiness appears. The pH is adjusted to 7.1 by adding concentrated NaOH, and the solution is placed in an oven at 40 °C for 2 h until complete solubilization. This visually clear solution is then placed at 4 °C after the addition of a volume of concentrated polysorbate 20 solution to obtain a final concentration of 52 mM. [000796] CA3a preparation process: Preparation of a co-polyamino acid / insulin glargine composition at pH 7.1, following a process using insulin glargine in liquid form (in solution) and a co-polyamino acid in liquid form (in solution). [000797] A 100-220 U / mL glargine solution containing the excipients described in Example C4 is added to a co-polyamino acid stock solution at pH 7.0-7.5. The concentrations of the excipients in the glargine solution are adjusted to obtain a concentration of 35 mM m-cresol and 230 mM glycerin in the co-polyamino acid / insulin glargine composition. A cloudiness appears. The pH is adjusted to 7.5 by adding concentrated NaOH, and the solution is placed in an oven at 40 °C for 2 h until complete solubilization. The resulting solution is visually clear. Preparation method: Preparation of a co-polyamino acid composition / insulin glargine at pH 7.1, following a process using insulin glargine in liquid form (in solution) and a co-polyamino acid in liquid form (in solution). [000798] To a co-polyamino acid stock solution at pH 7.0–7.5, a sodium chloride solution and a glargine solution at 100–220 U / mL, as described in Example C4, are added, in order. The concentrations of the excipients in the glargine solution are adjusted to obtain a concentration of 35 mM m-cresol and 230 mM glycerin in the co-polyamino acid / insulin glargine composition at pH 7.1. A cloudiness appears. The pH is adjusted to pH 7.5 by adding concentrated NaOH, and the solution is placed in an oven at 40 °C for 2 h until complete solubilization. The resulting solution is visually clear. [000799] According to preparation processes CA2, CA3, or CA3a and CA3b, co-polyamino acid / insulin glargine compositions have been prepared, for example, with insulin glargine concentrations between 100 U / mL and 300 U / mL. Example CA4: Preparation of co-polyamino acid / insulin olaraine 200 compositions U / mL at DH 7.1. [000800] Co-polyaminoacid / insulin glargine 200 U / mL compositions are prepared according to the processes described in CA2 and CA3 so as to obtain an insulin glargine concentration Cmsuiine glargine = 200 U / mL and a co-polyaminoacid concentration Cco-polyaminoaclde (mg / mL). These compositions are presented in Table 1 and the. Table 1: Compositions of insulin glargine (200 U / mL) in the presence of co-polyamino acid. Table a: Compositions of insulin glargine (200 U / mL) in the presence of co-polyamino acid B8. [000801] Co-polyamino acids allow insulin glargine to be solubilized at neutral pH and lead to a clear solution. CA5 preparation method: Protocol for determining the minimum concentration to solubilize insulin glargine at 50 U / mL at pH 7.1. [000802] Concentrated solutions of m-cresol and glycerin are added to a co-polyamino acid stock solution at pH 7-7.5. The amounts of excipients added are adjusted to obtain an m-cresol concentration of 35 mM and a glycerin concentration of 184 mM in a co-polyamino acid / insulin glargine 50 U / mL composition. [000803] In a 3 mL vial, 0.5 mL of an insulin glargine solution at a concentration of 100 U / mL, as described in Examples C3 or C4, is added to 0.5 mL of a co-polyamino acid / m-cresol / glycerin solution to obtain a co-polyamino acid (mg / mL) / insulin glargine 50 U / mL composition. A cloudiness appears. The pH is adjusted to pH 7.1 by adding concentrated NaOH, and the solution is placed in a static oven at 40 °C overnight. This procedure is performed for different concentrations of the co-polyamino acid. After overnight incubation at 40 °C, the samples are visually inspected and subjected to static light scattering at an angle of 173° using a Zetasizer (Malvern).The minimum co-polyamino acid concentration required to solubilize insulin glargine is defined as the lowest concentration at which the co-polyamino acid / insulin glargine mixture at pH 7.1 is visually clear and has a scattered intensity less than or equal to 1000 kcps (thousands of photons per second). The minimum concentrations of co-polyamino acid are presented in the following table lb. Table lb: Minimum co-polyamino acid concentration required to solubilize insulin glargine [000804] Co-polyamino acids B22, B7 and B13 allow insulin glargine to be solubilized with a mass concentration less than or equal to 0.88 mg / mL and with a hydrophobic molar / insulin glargine ratio less than or equal to 0.64. Table 1: Minimum ratio to solubilize insulin glargine. [000805] Co-polyamino acids B2, B3, B9, B15, B18, B19 and B21 allow insulin glargine to be solubilized with a mass concentration less than or equal to 1.25 mg / mL and with a co-polyamino acid / insulin glargine molar ratio less than or equal to 0.42. CA 6 preparation method: Determination of the minimum concentration to solubilize insulin glargine at 50 U / mL in the presence of sodium chloride at pH 7.1. [000806] The preparation process follows the CA5 preparation process with one difference: to the co-polyamino acid stock solution at pH 7-7.5, a concentrated sodium chloride solution is added to achieve the targets in the final composition, in addition to the m-cresol and glycerin solutions. The results are described in the following table. Table ld: Minimum ratios for solubilizing insulin glargine [000807] The addition of salt makes it possible to decrease the concentration of co-polyamino acid B22 to the threshold of glargine solubilization. Part CS - Compositions comprising insulin glargine and insulin lispro CB1 preparation method: Preparation of a diluted co-polyamino acid / insulin glargine 43 (U / mL) / insulin lispro 13.5 (U / mL) composition [000808] To a volume Vœ-polyaminoacid / insulin glargine diluted from the diluted co-polyaminoacid / insulin glargine 50 U / mL composition at pH 7.1 described in example CAI is added a volume Vmsuiine iispro of a lispro solution at 100 U / mL and water so as to obtain a co-polyaminoacid / insulin glargine 43 (U / mL) / insulin lispro 13.5 (U / mL) composition. CB2 i Preparation method: Preparation of a co-polyamino acid / insulin glargine / insulin lispro composition concentrated at pH 7.1 [000809] A co-polyamino acid / insulin glargine 43 (U / mL) / insulin lispro 13.5 (U / mL) composition described in Example CB1 is concentrated by ultrafiltration through a 3 kDa regenerated cellulose membrane (Amicon® Ultra-15 marketed by MILLIPORE). Following this ultrafiltration step, the retentate is clear, and the insulin glargine concentration in the composition is determined by reversed-phase chromatography (RP-HPLC). The insulin glargine concentrations The insulin lispro in the composition is then adjusted to the desired value by dilution in a solution of m-cresol / glycerin / Tween 20 excipients to obtain a final concentration of 35 mM m-cresol, 52 pM Tween, and an osmolarity of 300 mOsmol / kg. The pH is measured and adjusted, if necessary, to pH 7.1 by adding concentrated NaOH and HCl. This visually clear solution at pH 7.1 has an insulin glargine concentration of Cmsuime giargine (U / mL), an insulin lispro concentration of Gnsuime iispro = Cmsuime giargine x 0.33 and a co-polyaminoacid concentration of Cco-poiyammoacide (mg / mL) = Cco-polyaminoacid diluted (mg / mL) x Clnsullne giargine (U / mL) / 50 (U / mL). CB3 preparation method: Preparation of a co-polyamino acid / insulin glargine / insulin lispro composition concentrated at pH 7.1 [000810] To a volume Vco-polyaminoacid / insulin giargine concentrate of the co-polyaminoacid / insulin giargine concentrated composition at pH 7.1 described in Example CA3, a volume Vmsuime iispro of a lispro solution described in Example C2 is added. A volume of polysorbate 20 solution is also added to obtain a final concentration of 52 pM. The resulting solution, at pH 7.1, is visually clear and has a concentration of insulin giargine (Csu = giargine (U / mL)), a concentration of insulin lispro (Csu = giargine x 0.33), and a concentration of co-polyamino acid (Cε--polyaminoacid (mg / mL) = dilute Cε--polyaminoacid (mg / mL) x Cε--giargine (U / mL) / 50 (U / mL). The concentration of m-cresol is 35 mM and that of glycerin is 230 mM. CB4 preparation method: Preparation of a co-polyamino acid / insulin giargine 75 U / mL / insulin lispro 25 U / mL composition at pH 7.2 [000811] To a volume of the concentrated co-polyamino acid / insulin giargine composition at pH 7.2 described in Example CA3a or CA3b, a volume of a lispro solution described in Example C2 is added. The zinc concentration is adjusted to 0.5 mM by adding a volume of a concentrated ZnC solution. The pH is adjusted to 7.2 by adding a concentrated hydrochloric acid solution. The resulting visually clear solution has an insulin giargine concentration of 75 U / mL and an insulin lispro concentration of 25 U / mL. The m-cresol concentration is 35 mM and the glycerin concentration is 230 mM. CB5 preparation method: Preparation of a co-polyamino acid / insulin glargine 150 U / mL / insulin lispro 50 U / mL composition at pH 7.2 [000812] To a volume of the concentrated co-polyamino acid / insulin glargine composition at pH 7.2 described in Example CA4 or CAS, a volume of a lispro solution described in Example C2 is added. The zinc concentration is adjusted to 1 mM by adding a volume of a concentrated ZnC solution. The pH is adjusted to 7.2 by adding a concentrated hydrochloric acid solution. The resulting visually clear solution has an insulin glargine concentration of 150 U / mL and an insulin lispro concentration of 50 U / mL. The m-cresol concentration is 35 mM and the glycerin concentration is 230 mM. Example CB2 and CB3: Preparation of co-polyamino acid / insulin glargine 200 U / mL / insulin lispro 66 U / mL compositions at pH 7.1 [000813] Co-polyamino acid / insulin glargine 200 U / mL / insulin lispro 66 U / mL compositions are prepared according to one of the processes described in examples CB2 or CB3 so as to obtain an insulin glargine concentration Cmsuime glargine = 200 U / mL, an insulin lispro concentration C insu li ne iispro = 66 U / mL and a concentration of co-polyamino acid Cco-polyamino acid (mg / mL). These compositions are presented in Tables 2 and 2a. Table 2: Compositions of insulin glargine (200 U / mL) and insulin lispro (66 U / mL) in the presence of co-polyamino acid. Table 2a: Compositions of insulin glargine (200 U / mL) and insulin lispro (66 U / mL) in the presence of co-polyamino acid. Examples CB4 and CB5: Preparation of co-polyamino acid / insulin glargine / insulin lispro compositions at pH 7.2 [000814] Compositions of co-polyamino acid / insulin glargine 75 U / mL / insulin lispro 25 U / mL and compositions of co-polyamino acid / insulin glargine 150 U / mL / insulin lispro 50 U / mL are prepared according to the processes described in examples CB4 and CB5. Table 2b: Compositions of insulin glargine (75 and 150 U / mL) and insulin lispro (25 and 50 U / mL) in the presence of co-polyamino acid. [000815] Co-polyamino acids allow insulin glargine to be solubilized in the presence of insulin lispro at neutral pH and lead to a clear solution. [000816] Part CD - Results: Demonstration of the physical stability of the compositions according to the invention through the study of previously prepared compositions Example CD1: Accelerated stability at 25 °C in dynamic conditions [000817] Three 3 mL vials filled with 1 mL of co-polyamino acid / insulin glargine or co-polyamino acid / insulin glargine / prandial insulin are placed vertically on an orbital shaker. The shaker is placed in an oven at 25 °C and the vials are shaken at 250 rpm. The vials are visually inspected daily / weekly for the appearance of particulate matter. visible particles or turbidity. This inspection is carried out according to the recommendations of the European Pharmacopoeia (EP 2.9.20): the vials are subjected to illumination of at least 2000 lux and are observed against a white background and a black background. The number of days of stability corresponds to the duration after which at least two vials exhibit visible particles or are turbid. [000818] The accelerated stability result with co-polyamino acid B4 is presented in Table 3. Table 3: Stability results of the co-polyamino acid B4 / insulin glargine (200 U / mL) / insulin lispro (66 U / mL) composition at 25 °C under dynamic conditions. [000819] Co-polyamino acid B4 allows insulin glargine to be solubilized in the presence of insulin lispro at neutral pH and leads to a composition exhibiting good physical stability. Example CD2: Accelerated stability at 3 days °C [000820] At least five 3 mL cartridges filled with 1 mL of co-polyamino acid / insulin glargine / prandial insulin are placed in an oven at 30 °C under static conditions. The cartridges are visually inspected every two weeks to detect the appearance of visible particles or turbidity. This inspection is carried out according to the recommendations of the European Pharmacopoeia (EP 2.9.20): the cartridges are subjected to illumination of at least 2000 lux and are observed against a white background and a black background. The number of weeks of stability corresponds to the time after which the majority of the cartridges show visible particles or are turbid compared to a standard. [000821] The results of accelerated stability under static conditions are presented in the following table 4. Table 4: Stability results of co-polyamino acid / insulin glargine / insulin lispro compositions at 30 °C under static conditions. E ep > M -itatitm of insulin gtargine aprè£_mélanqe des compositions CQ- polvaminoacide / insulin olaroine 75 U / mL / Insulin lispro 25 U / mL avec albumin. [000822] This test demonstrates the precipitation of insulin glargine upon injection into a simulated physiological medium at physiological pH and ionic strength, containing albumin. These conditions allow for the simulation of the composition's behavior during subcutaneous injection. To 100 µL of a co-polyamino acid / insulin glargine 75 U / mL / insulin lispro 25 U / mL composition, 100 µL of a 20 mg / mL bovine albumin solution in a phosphate buffer at pH 7.4 is added. The phosphate buffer (PBS or phosphate buffer saline) is concentrated so that the NaCl and phosphate concentrations are 140 mM and 10 mM, respectively, after mixing with the composition. The precipitation of glargine in this medium is monitored at room temperature (20-25 °C) by absorbance measurements at 450 nm of the mixtures for 30 minutes. The absorbance measurements are performed using a UV-visible multi-well plate reader. [000823] The absorbance increases until it reaches a plateau. The precipitation time of glargine is defined as the time required for the measured absorbance to be greater than or equal to 80% of the plateau value. The precipitation times obtained with the compositions described above are shown in Table 5. Table 5: Precipitation time of insulin glargine after mixing the co-polyamino acid / insulin glargine / insulin lispro compositions with a medium that simulates the subcutaneous environment. [000824] The co-polyamino acid / insulin glargine / insulin lispro compositions of the invention lead to rapid precipitation of glargine after mixing with a medium that simulates the subcutaneous environment. Part D Pharmacokinetics Dl: Protocol for measuring the pharmacokinetics of insulin glargine and insulin lispro formulations. [000825] Studies in dogs were conducted with the aim of evaluating the pharmacokinetics of insulins after administration of a co-polyamino acid B22 / insulin glargine (150 U / mL) / insulin lispro (50 U / mL) composition. [000826] The pharmacokinetic profiles of insulin glargine (sum of circulating concentration of insulin glargine and its main metabolite M1) and insulin lispro were obtained for this composition. [000827] Ten animals that had been fasted for approximately 17.5 hours were injected subcutaneously with a dose of 0.68 U / kg of insulin. Blood samples were taken during the 16 hours following administration to characterize the pharmacokinetics of the insulins. Glargine, glargine-M1, and lispro levels were determined by a specific bioanalytical method. [000828] The pharmacokinetic parameters determined are as follows: - AUCo-1h, AUCo-2h, and AUCo-2h correspond to the area under the curve of insulin glargine (and its metabolite M1) concentrations as a function of time between 0 and 1 h, 0 and 2 h, and 10 and 16 h post-administration respectively; - AUCo-3omin, AUCo-1h, and AUCo-2h correspond to the area under the curve of insulin lispro concentrations as a function of time between 0 and 0.5 h, 0 and 1 h, and 8 and 16 h post-administration respectively; - AUCiast corresponds to the area under the curve between time 0 and the last measurement time taken on the subject. [000829] The following table 6 reports various pharmacokinetic parameters of insulin glargine and insulin lispro. Table 6: Mean pharmacokinetic parameters (ratio of means) of the CB5-6 composition comprising co-polyamino acid B22 / insulin glargine 150 U / mL / insulin lispro 50 U / mL. [000830] The results obtained show that, on the one hand, the glargine component of the formulation is absorbed rapidly (AUCo-ih and AUCo-2h) while retaining its basal character with significant coverage over the terminal part of the observation time (AUCio i6h). [000831] On the other hand, the lispro component is rapidly absorbed (AUCo-somin and AUCo-ih) and retains its prandial character. Indeed, no more lispro is observed beyond 8 hours (AUCs-ieh).

Claims

DEMANDS 1. Composition in the form of an aqueous solution for injection, having a pH between 6.0 and 8.0, comprising at least: a basal insulin whose isoelectric point pi is between 5.8 and 8.5; a co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy, said co-polyamino acid being composed of glutamic or aspartic units and said hydrophobic radicals Hy being of the following formula X: Formula X in which GpR is chosen from among the radicals of formulas VII, VIF or VU": ; GpG and GpH, identical or different, are chosen from the radicals of formulas XI or XI': Formula XF GpA is chosen from among the radicals of formula VIII Formula VIII In which A' is chosen from among the radicals of formula VIII', VIII" or VIII'" Formula VIII' Formula VIII" Formula VIII'" -GpL is chosen from among the radicals of formula XII Formula XII, GpC is a radical with formula IX Formula IX; the * indicate the attachment sites of the different groups linked by amide functions; a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 1, 2 or 3 if a = 1; a' is an integer equal to 1, 2 or 3 b is an integer equal to 0 or 1; c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; if e is different from 0 then at least one of the g, h or I is different from 0; and if a = 0 then 1 = 0; A, Ai, fia and A3, identical or different, are linear or branched alkyl radicals, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring, comprising from 1 to 8 carbon atoms; B is a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising from 1 to 9 carbon atoms or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and 1 to 5 oxygen atoms; C x is a linear or branched monovalent alkyl radical, possibly including a cyclic part, in which x indicates the number of carbon atoms and: ■ When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x < 25, ■ When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, * When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, * When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, * When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, G is a branched alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid function(s). R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched, comprising from 1 to 12 carbon atoms bearing one or more -CONH2 functions, or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and from 1 to 5 oxygen atoms: the hydrophobic radical(s) -Hy of formula X being linked to PLG: via a covalent bond between a carbonyl group of the hydrophobic radical -Hy and a nitrogen atom on the PLG, thus forming an amide function resulting from the reaction of an amine group on the PLG and an acid group on the precursor -Hy' of the hydrophobic radical -Hy, and via a covalent bond between a nitrogen atom of the hydrophobic radical -Hy and a carbonyl group on the PLG, thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical -Hy and an acid function on the PLG, the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between 0 < M < 0.5; When several hydrophobic radicals are carried by a co-polyamino acid, they are either identical or different. the degree of DP polymerization in glutamic or aspartic units for PLG chains is between 5 and 250; the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K + .

2. Composition according to claim 1, characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from the following co-polyamino acids of formula XXXa': formula XXXa' in which, D represents, independently, either a -CH2- group (aspartic unit) or a -CH2-CH2- group (glutamic unit), Hy is a hydrophobic radical chosen from among the hydrophobic radicals of formula X, in which r = 1 and GpR is a radical of Formula VII, Ri is a hydrophobic radical chosen from among the hydrophobic radicals of formula X in which r = 0 or r = 1 and GpR is a radical of formula VU', or a radical chosen from the group consisting of an H, a linear C2-C10 acyl group, a branched C4-C10 acyl group, a benzyl, a terminal 'amino acid' unit and a pyroglutamate, R.2 is a hydrophobic radical chosen from among the hydrophobic radicals of formula X in which r = 1 and GpR is a radical of Formula VII, or a radical -NR'R", R' and R" identical or different being chosen from the group consisting of H, linear or branched or cyclic alkyls in C2 to C10, benzyl and said R' and R" alkyls being able to form together one or more saturated, unsaturated and / or aromatic carbon rings and / or being able to include heteroatoms, chosen from the group consisting of O, N and S; - X represents a cationic entity chosen from the group comprising alkali cations; n + m represents the degree of polymerization DP of the co-polyamino acid, i.e. the average number of monomeric units per co-polyamino acid chain and 5 < n + m < 250.

3. Composition according to the preceding claim, characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from the co-polyamino acids of formulas XXXa', in which Ri = R'i and R å = R'2, with the following formula XXXa: Formula XXXa in which, m, n, X, D and Hy have the definitions given previously, R'i is a radical chosen from the group consisting of an H, a linear acyl group at C2 with C10, a branched acyl group at C4 with C10, a benzyl, a terminal "amino acid" unit and a pyroglutamate, R'2 is a radical -NR'R", R' and R" identical or different being chosen from the group consisting of H, linear or branched or cyclic alkyls in C2 to C10, benzyl and said R' and R" alkyls being able to form together one or more saturated, unsaturated and / or aromatic carbon rings and / or being able to include heteroatoms, chosen from the group consisting of O, IM and S.

4. Composition according to claim 2, characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from the co-polyamino acids of formula XXXa' in which n = 0 of the following formula XXXb: Formula XXXb in which m, X, D, Ri and R2 have the definitions given previously and at least Ri or R2 is a hydrophobic radical of formula X.

5. Composition according to claim 4 characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from the co-polyamino acids of formula XXXa' in which n = 0 of formula XXXb and Ri or R2 is a hydrophobic radical of formula X.

6. Composition according to claim any one of claims 4 and 5, characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from the co-polyamino acids of formula XXXb in which R2 is a hydrophobic radical of formula X in which r = 1 and GpR is of Formula VII.

7. A composition according to any one of claims 2 to 6, characterized in that Ri is a radical chosen from the group consisting of a linear acyl group in C2 to C10, a branched acyl group at C4 to C10, a benzyl, a terminal "amino acid" unit and a pyroglutamate.

8. Composition according to the preceding claim, characterized in that Ri is a radical selected from the group consisting of a linear acyl group in C2 to C10 or a branched acyl group in C4 to C10.

9. Composition according to any one of claims 2 to 8, characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from the co-polyamino acids of formulas XXXa', XXXa or XXXb in which the co-polyamino acid is selected from the co-polyamino acids in which the D group is a -CH2- group (aspartic unit).

10. A composition according to any one of claims 2 to 8, characterized in that the co-polyamino acid bearing carboxylate charges and hydrophobic radicals is selected from co-polyamino acids of formulas XXXa', XXXa, or XXXb, in which the co-polyamino acid is selected from co-polyamino acids in which group D is a -CH2-CH2- group (glutamic unit).

11. A composition according to any one of the preceding claims, characterized in that the basal insulin with an isoelectric point between 5.8 and 8.5 is insulin glargine.

12. Composition according to any one of the preceding claims, characterized in that it comprises between 40 and 500 U / mL of basal insulin having an isoelectric point between 5.8 and 8.

5.

13. Composition according to any one of the preceding claims, characterized in that the concentration of co-polyamino acid bearing carboxylate charges and hydrophobic radicals is at most 60 mg / mL.

14. Composition according to any one of the preceding claims, characterized in that the concentration of co-polyamino acid bearing carboxylate charges and hydrophobic radicals is at most 40 mg / mL.

15. Composition according to any one of the preceding claims, characterized in that the concentration of co-polyamino acid bearing carboxylate charges and hydrophobic radicals is at most 20 mg / mL.

16. Composition according to any one of the preceding claims, characterized in that the concentration of co-polyamino acid bearing carboxylate charges and hydrophobic radicals is at most 10 mg / mL.

17. Co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy, said co-polyamino acid being composed of glutamic or aspartic units and said hydrophobic radicals Hy chosen from the radicals of formula X as defined below: Formula X in which GpR is chosen from among the radicals of formulas VII, VIF or VU": GpG and GpH, identical or different, are chosen from the radicals of formulas XI or XI': * - NH - G - NH - * Formula XI Formula GpA is chosen from among the radicals of formula VIII Formula VIII In which A' is chosen from among the radicals of formula VIII', VIII" or VIII'" Formula VIII' Formula VIII" Formula VIII'" -GpL is chosen from among the radicals of formula XII Formula XII, GpC is a radical with formula IX Formula IX; The * indicate the attachment sites of the different groups linked by amide functions; - a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 1, 2 or 3 if a = 1; - a' is an integer equal to 1, 2 or 3; b is an integer equal to 0 or 1; - c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; d is an integer equal to 0, 1 or 2; e is an integer equal to 0 or 1; - g is an integer equal to 0, 1, 2, 3, 4, 5 or 6; h is an integer equal to 0, 1, 2, 3, 4, 5 or 6, and at least one of g, h or I is different from 0; - I is an integer equal to 0 or 1 and I' = 1 if I = 0 and G = 2 if I = 1; r is an integer equal to 0, 1, or 2, and s' is an integer equal to 0 or 1; and if e is different from 0 then at least one of the g, h or I is different from 0; and if a = 0 then 1 = 0; A, Ai, Ai and A3, identical or different, are linear or branched alkyl radicals comprising from 1 to 8 carbon atoms, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring; B is an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms, or a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising 1 to 9 carbon atoms. Cx is a linear or branched monovalent alkyl radical possibly including a cyclic portion, in which x indicates the number of carbon atoms and: ■ When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x < 25, ■ When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, * When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, * When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, * When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, G is a linear or branched divalent alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid function(s), R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched comprising from 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched comprising from 1 to 12 carbon atoms bearing one or more -CONH2 functions, or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and 1 to 5 oxygen atoms, The hydrophobic radical(s) -Hy of formula X being linked to PLG: via a covalent bond between a carbonyl group of the hydrophobic radical -Hy and a nitrogen atom on the PLG, thus forming an amide function resulting from the reaction of an amine function on the PLG and an acid function on the precursor -Hy' of the hydrophobic radical -Hy, and via a covalent bond between a nitrogen atom of the hydrophobic radical -Hy and a carbonyl atom attached to the PLG, thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical -Hy and an acid function carried by the PLG, the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between 0 < M < 0.5; When several hydrophobic radicals are carried by a co-polyamino acid, they are either identical or different. the degree of DP polymerization in glutamic or aspartic units for PLG chains is between 5 and 250; the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K + .

18. Precursor Hy' of the hydrophobic radical -Hy of formula X' as defined below: Formula X' in which GpR is chosen from the radicals of formulas VII, VU' or VII' Formula VII' or * _ li_ R JJ _ * Formula VU' GpG and GpH, identical or different, are chosen from the radicals of formulas XI or XI': * - NH - G - NH - * Formula XI Formula GpA is chosen from among the radicals of formula VIII Formula VIII In which A' is chosen from the radicals of formula HIV', VIII" or HIV' Formula VIII' Formula VIII' Formula VIII'" -GpL is chosen from among the radicals of formula XII Formula XII, GpC is a radical with formula IX: Formula IX; the * indicate the attachment sites of the different groups linked by amide functions; a is an integer equal to 0 or 1 and a' = 1 if a = 0 and a' = 1, 2 or 3 if a = 1; a' is an integer equal to 1, 2 or 3; b is an integer equal to 0 or 1; c is an integer equal to 0 or 1, and if c is equal to 0 then d is equal to 1 or 2; d is an integer equal to 0, 1 or 2; e is an integer equal to 0 or 1; g is an integer equal to 0, 1, 2, 3, 4, 5 or 6; h is an integer equal to 0, 1, 2, 3, 4, 5 or 6, and at least one of g, h or I is different from 0; I is an integer equal to 0 or 1 and I' = 1 if I = 0 and I' = 2 if I = 1; r is an integer equal to 0, 1, or 2, and s' is an integer equal to 0 or 1; and if e is different from 0 then at least one of the g, h or I is different from 0; and if a = 0 then 1 = 0; A, Ai, A2 and A3, identical or different, are linear or branched alkyl radicals comprising 1 to 8 carbon atoms, and possibly substituted by a radical from a saturated, unsaturated or aromatic ring; B is an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms, or a linear or branched alkyl radical, possibly comprising an aromatic ring, comprising 1 to 9 carbon atoms. Cx is a linear or branched monovalent alkyl radical possibly including a cyclic portion, in which x indicates the number of carbon atoms and: "When the hydrophobic radical -Hy carries 1 -GpC, then 9 < x < 25, ■ When the hydrophobic radical -Hy carries 2 -GpC, then 9 < x < 15, • When the hydrophobic radical -Hy carries 3 -GpC, then 7 < x < 13, « When the hydrophobic radical -Hy carries 4 -GpC, then 7 < x < 11, ■ When the hydrophobic radical -Hy carries at least 5 -GpC then, 6 < x < 11, G is a linear or branched divalent alkyl radical of 1 to 8 carbon atoms, said alkyl radical bearing one or more free carboxylic acid function(s), R is a radical chosen from the group consisting of a divalent alkyl radical, linear or branched comprising from 1 to 12 carbon atoms, a divalent alkyl radical, linear or branched comprising from 1 to 12 carbon atoms bearing one or more -CONH2 functions, or an unsubstituted ether or polyether radical comprising from 4 to 14 carbon atoms and 1 to 5 oxygen atoms, The hydrophobic radical(s) -Hy of formula X being linked to PLG: via a covalent bond between a carbonyl group of the hydrophobic radical -Hy and a nitrogen atom on the PLG, thus forming an amide function resulting from the reaction of an amine function on the PLG and an acid function on the precursor -Hy' of the hydrophobic radical -Hy, and via a covalent bond between a nitrogen atom of the hydrophobic radical -Hy and a carbonyl atom attached to the PLG, thus forming an amide function resulting from the reaction of an amine function of the precursor -Hy' of the hydrophobic radical -Hy and an acid function carried by the PLG, the ratio M between the number of hydrophobic radicals and the number of glutamic or aspartic units being between G < M < 0.5; - when several hydrophobic radicals are carried by a co-polyamino acid, then they are either identical or different. the free carboxylic acid functions being in the form of a salt of an alkali cation chosen from the group consisting of Na + and K+ .

19. Use of ionic species selected from the group of anions, cations and / or zwitterions to improve the physico-chemical stability of compositions.