Powder of non-nanoscale guanine particles and uses thereof in cosmetics

Abstract

The present invention relates to a method for preparing, by means of physicochemical polishing, a powder of non-nanoscale guanine particles, wherein all the dimensions of the particle have a minimum size greater than 100 nm and the particles have a single "alpha" polymorphic form, characterized in that the method comprises the following steps: (i) suspending the guanine particles (i1) in a basic aqueous solution or alternatively (i2) in an acidic solution, the base or alternatively acid concentrations being lower than the concentrations allowing the formation of guanine salts; (ii) filtering and recovering the particles; (iii) sequentially washing the particles with aqueous solutions having a decreasing base concentration when step (i) is carried out (i1) in a basic medium or alternatively with aqueous solutions having a decreasing acid concentration when step (i) is carried out (i2) in a basic medium, followed by rinsing the particles with water; and (iv) recovering, in particular by filtration, a powder of non-nanoscale particles having a single "alpha" polymorphic form.

Description

[0001] Non-nanometric guanine particle powder and its uses in cosmetics

[0002] FIELD OF INVENTION

[0003] The present invention relates to a process for preparing non-nanometric guanine particles, said particles and their uses in the field of cosmetics.

[0004] STATE OF THE ART

[0005] Guanine is generally found in powder form, containing nanoparticles (at least one dimension of which is less than 100 nm) that can diffuse through the skin and are therefore not permitted in cosmetics. Non-nanometric guanine particles are thus sought.

[0006] The removal of fine particles (smaller than 100 nm) can be achieved through a dissolution and recrystallization process called maturation, leading to what is known as Ostwald ripening (i.e., the growth of larger particles at the expense of smaller ones). However, it is not only the fine particles that will be affected by this treatment. Indeed, the size, morphology (textural properties), surface state of the particles, state of aggregation, crystallinity, polymorphic shape, and structural purity are all interrelated solid-state characteristics that will be affected by the dissolution-recrystallization treatment and may change.

[0007] Furthermore, due to its high melting point, guanine has very low solubility in water at neutral pH, and temperature cycling in water and acceptable organic solvents does not allow for the removal of these fine particles in a reasonable timeframe, while the larger particles are removed. Moreover, in its solid state, guanine has two alpha and beta polymorphic forms, which can pose stability problems, as well as a monohydrate and several hydrated salts (phosphate, hydrochloride, sodium salt).

[0008] Therefore, the need remains to develop a new process for obtaining non-nanometric guanine particles, while preserving or even improving their solid-state characteristics, such as particle surface state, aggregation state, crystallinity, polymorphic shape, and structural purity, without impacting their coverage properties. Structural purity is notably defined by Coquerel, G., in "The 'structural purity' of molecular solids—An elusive concept?", Chem. Eng. Process 2006, 45, 857–862.The inventors have rightly demonstrated that the use of a physicochemical polishing process, in particular in a double-jacketed reactor, preferably a Couette-Taylor type reactor, comprising in particular a step (i) of suspending the guanine particles (i1) in a basic solution or alternatively (i2) in an acidic solution, followed by sequential washings (iii) of said particles with aqueous solutions of decreasing concentration in base when step (i) is carried out (i1) in a basic medium or alternatively in acid when step (i) is carried out (i2) in an acidic medium; followed by rinsing with water, made it possible to promote the obtaining of a single stable polymorphic form with good crystallinity and the presence of crystals with dimensions greater than 100 nm.

[0009] To the Applicant's knowledge, this is the first time the Couette-Taylor process has been used on guanine, allowing control over both crystal size and the polymorphic shape of the particles. The short residence times will minimize any potential chemical degradation of the guanine.

[0010] DESCRIPTION OF THE INVENTION

[0011] A first object of the invention is a process for preparing, by physico-chemical polishing, a powder of non-nanometric guanine particles, all of whose particle dimensions have a minimum size greater than 100 nm and of a unique polymorphic "alpha" shape, characterized in that the process comprises the following steps:

[0012] (i) suspension of guanine particles (i1) in a basic aqueous solution or alternatively (i2) in an acidic aqueous solution, the concentrations of base or alternatively of acid being lower than the concentrations allowing the formation of guanine salts,

[0013] (ii) filtration and recovery of said particles.

[0014] (iii) sequential washing of said particles with aqueous solutions of decreasing base concentration when step (i) is carried out (ii) in a basic medium or alternatively with aqueous solutions of decreasing acid concentration when step (i) is carried out (ii) in an acidic medium, followed by rinsing with water, and

[0015] (iv) recovery, in particular by filtration, of a powder of non-nanometric guanine particles and of unique polymorphic shape "alpha".

[0016] The sequential washings of step (iii) are advantageously interspersed with filtrations (ii) to prevent uncontrolled precipitation of the dissolved material and the reformation of nanoparticles. The present invention also relates to a non-nanometric guanine particle powder, all particle sizes of which have a minimum size greater than 100 nm, obtained according to the preparation process defined in the invention.

[0017] The present invention also relates to a powder of non-nanometric guanine particles, characterized in that all particle dimensions have a minimum size greater than 100 nm and in that it is of a unique polymorphic "alpha" shape, comprising "alpha" shaped particles and less than 5% by weight, or even less than 1% by weight of "beta" shaped particles, or even is free of "beta" shaped particles.

[0018] Another object of the invention relates to a cosmetic composition comprising, in a physiologically acceptable medium, a powder of non-nanometric guanine particles, all of whose particle dimensions have a minimum size greater than 100 nm as defined above, and at least one additional cosmetic ingredient.

[0019] The present invention also relates to a cosmetic process for the care and / or makeup of keratinous materials comprising the application to said keratinous materials of a cosmetic composition as defined according to the invention.

[0020] FIGURES

[0021] Figure 1 Schematic representation of the Couette-Taylor reactor used for the polishing step.

[0022] Figure 2 Comparison of the X-ray diffractograms of a structurally pure alpha guanine, an initial a+p guanine from the supplier TCI and the calculated diffractogram of the structurally pure beta.

[0023] Figure 3 Comparison of X-ray diffractograms of a guanine from supplier TCI and a guanine obtained according to the process of the invention described in example 1-1 (double jacket reactor and isothermal batch mode) (pure alpha form with good crystallinity).

[0024] Figure 4a SEM image of the starting Guanine TCI (a+p mixture, magnification X20000).

[0025] Figure 4b: SEM image of the starting TCI Guanine (a+p mixture, magnification X50000). Figure 5a: SEM image of the overall appearance of the guanine aggregates obtained according to the process of the invention of Example 1-1 bis (Couette Taylor isothermal mode), magnification X20000.

[0026] Figure 5b: SEM image of the detail of the morphology and size of the guanine particles obtained according to the process of example 1-1 bis (Couette Taylor isothermal mode), magnification X50000.

[0027] Figure 6a: SEM image of a guanine particle powder obtained according to the process of example 1-2 (non-isothermal Couette Taylor), magnification X20000.

[0028] Figure 6b: SEM image of a guanine particle powder obtained according to the process of example 1-2 (non-isothermal Couette Taylor), magnification X50000.

[0029] Figure 7: X-ray diffraction pattern on guanine TCI powder after 15 min of polishing in a non-isothermal Couette Taylor mode (1 N NaOH), with a single intermediate wash with a 10' NaOH basil solution 5 M, then a final wash with water.

[0030] Figure 8: X-ray diffraction pattern on powdered guanine TCI after polishing as described in Example 5(a), and after sequential washings with recycled NaOH 10' 1 M (b), NaOH 10' 3 M (c) and NaOH 10' 5 M, and rinses with 10' NaOH 6 M and water (d).

[0031] Figure 9: X-ray diffraction pattern on powder of TCI guanine after polishing under acidic conditions as described in Example 6 (a), and after washing (b) compared to guanine obtained with the process according to the invention under basal conditions (c).

[0032] Figure 10: SEM image of a guanine particle powder obtained according to the process of example 6. This image shows the particle size distribution of the powder at the end of polishing under acidic conditions and subsequent washing.

[0033] Figure 11: Zoom of Figure 10 on the guanine particle powder obtained according to the process of Example 6 after the polishing step under acidic conditions and the subsequent washing. DETAILED DESCRIPTION OF THE INVENTION

[0034] The present invention therefore relates in particular to a process for preparing, by physico-chemical polishing, a powder of non-nanometric guanine particles, all of whose particle dimensions have a minimum size greater than 100nm and of a unique polymorphic "alpha" shape, characterized in that the process comprises the following steps:

[0035] (i) suspension of guanine particles (i1) in a basic aqueous solution or alternatively (i2) in an acidic solution, the concentrations of base or alternatively of acid being lower than the concentrations allowing the formation of guanine salts,

[0036] (ii) filtration and recovery of said particles,

[0037] (iii) sequential washing of said particles with aqueous solutions of decreasing base concentration when step (i) is carried out (ii) in a basic medium or alternatively with aqueous solutions of decreasing acid concentration when step (i) is carried out (ii) in an acidic medium, followed by rinsing with water, and

[0038] (iv) recovery, in particular by filtration, of a powder of non-nanometric guanine particles and of unique polymorphic shape "alpha".

[0039] By 'physico-chemical polishing' according to the invention, it is understood that the process according to the invention makes it possible to obtain a polishing of the particles, in other words the particles have a smoother surface state, with a transformation of particles of various polymorphic shapes into particles of a single polymorphic shape - the most stable at room temperature - by means of a step of (i) suspending said particles (i1) in a basic solution or alternatively (i2) in an acidic solution, the concentrations of base or alternatively of acid being lower than the concentrations allowing the formation of guanine salts; followed by sequential washings of said particles with aqueous solutions of decreasing concentration of base when step (i) is carried out (i1) in a basic medium or alternatively aqueous solutions of decreasing concentration of acid when step (i) is carried out (i2) in an acidic medium.

[0040] By 'unique polymorphic form' according to the invention, we mean a unique crystalline form, that is to say, one devoid of any other solid form; in other words, the powder comprises a single crystalline lattice and is free of amorphous particles. In the case of guanine according to the invention, this is a unique 'alpha' polymorphic form, that is to say, one comprising particles of the unique alpha form and less than 5% by weight, or even less than 1% by weight, of beta-form particles, or even free of beta-form particles. The guanine powder obtained according to the process of the invention is well crystallized; in other words, it has good crystallinity. Crystallinity refers to the degree of long-range structural order in a solid: it determines the degree of regularity of the 3D organization of crystalline compounds. It is zero for vitreous and amorphous compounds.Crystallinity can be assessed using various methods, such as those described in the review by Shah et al., *Journal of Pharmaceutical Sciences*, Vol. 95, No. 8, August 2006, and the review by Ilhan Uzun, *Journal of Polymer Research* (2023) 30:394. In one particular method, good crystallinity is assessed by the height of X-ray diffraction peaks, the resolution of peak clusters, and their full width at half maximum (FWHM). Alternatively, the area of ​​all peaks can be taken and the area between the baseline and a function that passes through all peak minima can be subtracted.

[0041] In the rest of the description we will speak of a guanine powder of unique polymorphic form or of unique crystalline form, it being understood that the powder obtained has good crystallinity.

[0042] In the description, we will speak interchangeably of 'nanometric particles' or 'nanoparticles' and conversely of 'non-nanometric particles', 'non-nano particles' or 'non-nanoparticles' or 'particles in which all dimensions of the particle have a minimum size greater than 100nm'.

[0043] Step (i) of physicochemical polishing

[0044] The physicochemical polishing according to the invention comprises a succession of dissolutions / recrystallizations designed to dissolve the finest particles and preferentially dissolve particles of metastable polymorphic shapes, followed by sequential washings (steps of progressive neutralization) to obtain a single and stable crystalline form.

[0045] The general principle of the process according to the invention consists of placing populations of guanine particles (11) in alkaline solutions (also called basic solutions) or alternatively (12) in acidic solutions to dissolve the nanoparticles. The concentrations of acids or bases will be limited to prevent the formation of the corresponding salts. A first step (1) comprises suspending the guanine particles (11) in a basic aqueous solution or alternatively (12) in an acidic aqueous solution, the concentrations of base or alternatively acid being lower than the concentrations allowing the formation of guanine salts, in order to prevent the reformation of nanoparticles during the stepwise neutralization.

[0046] This step is carried out in batch or continuous mode (understood as covering semi-continuous and continuous modes) in a double-jacketed reactor. According to a particular preferred mode, this step is carried out continuously (semi-continuously) in a Couette-Taylor type reactor.

[0047] By 'Couette Taylor type reactor' which is the preferred reactor according to the invention, we mean a reactor comprising two cylinders, each having a double jacket, the inner cylinder rotating at a defined speed while the outer cylinder is fixed, and the two cylinders being advantageously regulated in temperature independently.

[0048] The Couette-Taylor type reactor is shown in Figure 1. It was manufactured by Laminar Co., Ltd (South Korea). It has a capacity of 93 ml and is placed horizontally to eliminate any hydrostatic pressure effects.

[0049] In a specific configuration, the inner cylinder (radius = 19.5 mm) rotates at speeds between 30 rpm and 1200 rpm while the outer cylinder (radius = 23.4 mm) remains stationary. The gap between the two cylinders is 3.9 mm.

[0050] The two cylinders are independently temperature-controlled, with T1 being the setpoint temperature of the inner cylinder's thermostat and T2 the setpoint temperature of the outer cylinder's thermostat. Thus, the reactor can be used in isothermal mode (T1 = T2) and non-isothermal mode (T1 = T2). The inner and outer cylinder temperatures are controlled by a Lauda Proline RP890 and a Lauda Proline RP845, respectively.

[0051] The filtering device can be, for example: a Büchner funnel, a sintered glass, or a centrifuge used alone or in tandem, or continuous filtration devices (e.g., belt filter, modular screw filter).

[0052] The use of a continuous Couette-Taylor reactor is notably described by Bowen Zhang et al. (2025) and Marc L. (2024). The polishing conditions (e.g., temperature, duration, acid or base concentration) are adapted to the guanine and the acid or base chosen for the solution used in polishing step (i) so that the guanine is stable in this medium and not one of its salts.

[0053] According to a particular method, the process of the invention uses the following conditions:

[0054] Temperature: from 20°C to 95°C;

[0055] Duration: from 5 minutes to 20 hours, and

[0056] Concentration of acid or base of the solution used for the polishing steps (i) which is less than the concentration allowing the formation of guanine salts, in order to avoid the reformation of nanoparticles during the step neutralization.

[0057] According to a particular method, the polishing step (i) comprises suspending the guanine powder, under agitation, (ii) in a basic solution or alternatively (i2) in an acidic solution, at a temperature ranging from 20°C to 95°C, for a duration ranging from 5 minutes to 20 hours. According to a particular method as illustrated in the examples below, the duration is 15 minutes.

[0058] According to the process of the invention, the base (or acid) concentration of the guanine suspensions in the basic solution, or alternatively the acidic solution, in step (i), is lower than that required for salt formation, to prevent the subsequent reformation of nanoparticles during the stepwise neutralization. Indeed, the inventors observed that, for example, in a highly concentrated phosphoric acid suspension (between 7 M and 2.5 M), the guanine particles will be transformed into dihydrogen phosphate monohydrate: Guanine - H3PO4-I H2O. Suspending guanine in 2 M hydrochloric acid leads to the formation of dihydrate hydrochloride: Guanine - HCl- 2H2O. And the subsequent salting out of these salts will reform nanoparticles.

[0059] Thus, according to a first embodiment, the basic solution comprises a base chosen from: NaOH, Na2COa, K2CO3, KOH, NH4OH, Ca(OH)2, and mixtures thereof.

[0060] A person skilled in the art will adjust the concentration of the base to be used (il) in the basic solution of step (i), according to the type of base, it being understood that the concentration of the base solution must be less than that required to form the guanine salt.

[0061] For the NaOH base, a concentration ranging from 0.1 M to 1.66 M, and in particular less than 1.8 M, is preferred for the basic solution in step (i). At a given temperature, the higher the base concentration in step (i), the faster the polishing, but the greater the number of sequential washes (iii) required to obtain the single-shape 'alpha' non-nanometric guanine particle powder.

[0062] At a given temperature and conversely, the lower the base concentration at step (i), the slower the polishing, but the smaller the number of sequential washes (iii) required to obtain the unique 'alpha' shape non-nanometric guanine particle powder.

[0063] A person skilled in the art will therefore adjust the concentration, temperature, and duration of the process according to the invention to optimize the process for industrial production. Regarding temperature, the higher it is, the faster the polishing will be.

[0064] Thus, according to a particular method, step (i) includes suspending the guanine powder, under agitation, in a 1 M NaOH basic solution, at a temperature of 20°C for a period ranging from 5 minutes to 20 hours.

[0065] According to another embodiment, the acid solution comprises an acid selected from HCl, H2SO4, H3PO4, HNO3, HCIO4, and mixtures thereof.

[0066] A person skilled in the art will adjust the concentration of the acid to be used in the acid solution of step (i), according to the type of acid, it being understood that the concentration of the acid solution must be less than that which enables the formation of the guanine salt.

[0067] Thus, for H3PO4 acid, a concentration ranging from 0.2 M to 2.0 M will be used, in particular less than 2.125 M for the acid solution in step (i).

[0068] According to a preferred mode, the concentration of acid or alternatively base is sufficient to ensure rapid maturation kinetics (Ostwald ripening) and therefore acceptable productivity in the context of an industrial application.

[0069] In particular, the polishing step (i) is carried out in isothermal mode or alternatively with cyclic temperature variations otherwise named 'non-isothermal'.

[0070] According to a first particular method, the reaction is carried out isothermally. By 'isothermal method' according to the invention, it is understood that the polishing is performed at a constant temperature. The polishing temperature will generally range from 20 to 95°C.

[0071] According to another particular and preferred method, polishing is carried out using a method with temperature cycles.

[0072] By 'mode with temperature cycles' (also called 'non-isothermal mode') according to the invention, it is understood that the polishing is carried out by cycles with a temperature / time profile repeated over a given period.

[0073] According to this 'non-isothermal' or temperature-cycling mode, a temperature gradient can be used. It can be spatial, with two reactors regulated at different temperatures and connected to each other, the suspension circulating between the two reactors. It can also be temporal, with cyclic temperature programming based on time. In the case of a Couette-Taylor reactor, the two cylinders can be set to two different temperatures or, conversely, to the same temperature.

[0074] As an example, and as illustrated in the examples below, the guanine suspension is subjected to temperature cycles (temperature gradient between the outer reactor and the inner reactor), for example for 15 minutes.

[0075] Finally, the acidic or alternatively basic solutions used for the polishing steps have primarily a catalytic action and can therefore be recycled for successive operations. The associated benefit is improved yield. The solutions used for sequential washing can also be reused several times.

[0076] Thus, in an advantageous manner, the solution obtained in step (i) is reused as a catalyst in another batch, to treat new guanine particles according to the same process.

[0077] A skilled professional can thus optimize the polishing parameters to improve particle size distribution, structural purity, and yield, particularly by adjusting the following parameters:

[0078] - the concentration of acid (or alternatively base) and the quantity of acid (or alternatively base) relative to a unit mass of guanine;

[0079] - the temperature in isothermal mode (or with thermal oscillations); and - the residence time (duration) in the reactor in batch or continuous (semi-continuous) mode with a Couette-Taylor type reactor;

[0080] Other parameters such as the type and intensity of agitation, the presence or absence and intensity of ultrasound, the presence and concentration of additive(s), may also influence the polishing kinetics on an industrial scale.

[0081] The examples illustrated below have shown that, simultaneously with the disappearance of nanoparticles, the structural purity of the solid phase improves towards a single polymorphic form, such as the pure alpha form for example for guanine following the irreversible scheme: Physical mixture a + p — > pure a.

[0082] Since the a form is stable at room temperature and well above 100°C, the final product contains exclusively the relaxed a form with good crystallinity. This solid phase is therefore less susceptible to chemical and / or physical changes over time. Initial tests showed that coverage was not affected by the nanoparticle removal treatment.

[0083] Step (ii) of filtration and recovery of said particles

[0084] The filtering device, particularly in a Couette-Taylor type reactor, can be, for example: a Büchner, a sintered glass, or a centrifuge, used alone or in tandem, or continuous filtration devices (e.g., belt filter, modular screw filter).

[0085] According to a particular method, the filtering device is sintered glass of porosity No. 3 (from 16 to 40 pm) or preferably No. 4 (from 10 to 16 pm).

[0086] This filtering device thus makes it possible to separate non-nanometric guanine particles, all of whose particle dimensions have a minimum size greater than 100nm, from the mother solution.

[0087] The solid guanine particles deposited on a filter device and retained during filtration can be referred to as "filter cake".

[0088] Step (iii) of sequential washings (“neutralization”) The process according to the invention comprises (iii) sequential washings of said guanine particles with aqueous solutions of decreasing concentration of base or alternatively of acid (depending on whether step (i) was carried out with (i1) a basic medium or alternatively (i2) an acidic medium), allowing a return to neutral pH by progressive steps, advantageously interspersed with filtrations in order not to cause uncontrolled precipitation of the dissolved guanine and thus reform nanoparticles.

[0089] 'Sequential washes' means at least 2 washes performed in sequence.

[0090] Thus, according to a first embodiment, the basic solution comprises a base selected from NaOH, Na2COs, K2CO3, KOH, NH4OH, Ca(OH)2, and mixtures thereof, at a concentration lower than that required to form guanine salts, in order to prevent the reformation of nanoparticles during the stepwise neutralization. Preferably, the basic solution comprises NaOH at a concentration ranging, in particular, from 0.1 M to 1.66 M, especially less than 1.8 M for the basic solution in step (i), and at decreasing base concentrations down to 10⁻¹⁰ M. 5 M for the basic solutions of step (iii).

[0091] Indeed, if the solution is too alkaline (for example, NaOH equal to or greater than 1.8 M), then it is the hydrated sodium salt that crystallizes. Similarly, if the solution is too acidic—with H3O4 equal to or greater than 2.125 M, for example—then it will be the hydrated phosphate that crystallizes.

[0092] The return of these salts to guanine alone will recreate nanoparticles and will therefore be counterproductive.

[0093] According to another embodiment, the acid solution comprises an acid selected from HCl, H2SO4, H3PO4, HNO3, HCI4, and mixtures thereof, at a concentration lower than that required to form guanine salts, in order to prevent the reformation of nanoparticles during the stepwise neutralization. Preferably, the acid solution comprises H3PO4 at a concentration ranging, in particular, from 0.2 M to 2.0 M for the acid solution in step (i), which must be less than 2.125 M, and at decreasing acid concentrations down to 10⁻¹⁰ M. 5 M for acidic solutions from step (iii).

[0094] To increase the overall yield of guanine polishing, it is advantageous to wash successive filter cakes with basic or, alternatively, acidic solutions saturated with guanine. A "saturated guanine solution" here refers to a solution that can no longer dissolve any more guanine at the working temperature and the concentration of acid or base used.

[0095] This step (iii) of sequential washings with decreasing concentrations of base or alternatively aqueous solutions with decreasing concentrations of acid depending on whether step (i) is carried out (il) in basic medium or alternatively (i2) in acidic medium, is followed by a water rinse.

[0096] Step (iv) of particle recovery

[0097] The powder of non-nanometric guanine particles and of unique polymorphic shape is then recovered by a recovery step (iv), in particular by filtration.

[0098] The filtering device is as described in step (ii).

[0099] In one particular embodiment, the process according to the invention comprises the following steps:

[0100] (i) suspension of guanine particles in a basic aqueous solution, preferably a basic aqueous solution comprising NaOH, the base concentration being lower than the concentration allowing the formation of guanine salts, such as a concentration of 1M when the base is NaOH,

[0101] (ii) filtration and recovery of said particles,

[0102] (iii) sequential washing of said particles with aqueous solutions of decreasing base concentration, preferably with aqueous solutions of decreasing base concentration saturated with guanine, for example with NaOH solutions of successive concentrations 10' 1 M, 10' 3 M and 10' 5M, the washings being preferably interspersed with filtrations; and then followed by a wash and rinse with water, and

[0103] (iv) recovery, in particular by filtration, of a powder of non-nanometric guanine particles and of unique polymorphic shape "alpha".

[0104] As an example for the sequential washings of step (iii) according to this embodiment: the filter cake (solid particles recovered from the filter in step ii) is washed with a 10' NaOH solution 1 M saturated with guanine and then filtered; and the resulting filter cake is rinsed with a 10' NaOH solution 2 M saturated with guanine, then the filtration cake is washed with a 10' NaOH solution 3 M saturated with guanine and then filtered; and the resulting filter cake is rinsed with a 10' NaOH solution 4 M saturated with guanine, then the filtration cake is washed with a 10' NaOH solution 5M saturated with guanine and then filtered; and the resulting filter cake is rinsed with a 10' NaOH solution 6 M, then the filter cake is washed and rinsed with water and filtered.

[0105] In one particular embodiment, the process according to the invention comprises the following steps:

[0106] (i) suspension of guanine particles in an acidic aqueous solution, preferably an acidic aqueous solution comprising H3PO4, the acid concentration being lower than the concentration allowing the formation of guanine salts, such as a concentration of 2 M when the acid is H3PO4, preferably at reflux temperature under an atmosphere,

[0107] (ii) filtration and recovery of said particles,

[0108] (iii) sequential washing of said particles with aqueous solutions of decreasing acid concentration, preferably with aqueous solutions of decreasing acid concentration saturated with guanine, for example with a 0.5 M HsPCl solution, preferably at a temperature of 60°C, the washing preferably being followed by filtration; and then followed by washing and rinsing with water, preferably after cooling, preferably at ambient temperature, and

[0109] (iv) recovery, in particular by filtration, of a powder of non-nanometric guanine particles and of unique polymorphic shape "alpha".

[0110] Powder of no

[0111] The present invention also relates to a powder of non-nanometric guanine particles in which all particle dimensions have a minimum size greater than 100nm, obtained according to the preparation process defined according to the invention.

[0112] The present invention also relates to a non-nanometric guanine particle powder characterized in that all particle dimensions have a minimum size greater than 100 nm and in that it comprises unique alpha (stable) shape particles and less than 5% by weight, or even less than 1% by weight of beta shape particles, or even free of beta shape particles.

[0113] Another object of the invention relates to a cosmetic composition comprising, in a physiologically acceptable medium, a powder of non-nanometric guanine particles, all of whose particle dimensions have a minimum size greater than 100 nm as defined above, and at least one additional cosmetic ingredient.

[0114] By "cosmetic composition" we mean any composition intended for cosmetic purposes, that is to say aesthetic purposes, which may be brought into contact with the superficial parts of the human body and more particularly with keratinous materials, in particular human skin and / or lips.

[0115] By "physiologically acceptable medium" we mean any excipient suitable for topical use, in contact with keratinous materials, without risk of toxicity, incompatibility, instability and / or allergic response.

[0116] The additional cosmetic ingredient may be chosen from emollients, oils, surfactants, gelling and / or structuring agents, fillers, pigments, cosmetic actives, preservatives, perfumes, and mixtures thereof.

[0117] The composition may be a skincare composition and / or a makeup composition of keratinous materials.

[0118] According to the invention, "keratinous materials" means: skin and / or its appendages, in particular: nails, eyelashes, eyebrows, lips, and more particularly human skin and / or lips.

[0119] The composition may be in any form suitable for topical application to keratinous materials, such as, for example, a cream, a serum, a lotion, an oil, a powder, a balm, or a stick, without this being limiting.

[0120] The non-nanometric guanine particle powder, all of whose particle dimensions have a minimum size greater than 100 nm as defined above, may represent from 0.001% to 30% by weight relative to the total weight of the composition, in particular from 0.01% to 25%, in particular from 1% to 15% by weight relative to the total weight of the composition.

[0121] Process

[0122] The present invention also relates to a cosmetic process for the care and / or makeup of keratinous materials comprising the application to said keratinous materials of a cosmetic composition as defined according to the invention.

[0123] The composition is as described previously.

[0124] The present invention will now be illustrated in the following non-limiting examples.

[0125] Percentages are expressed as a percentage of raw material weight relative to the total weight of the composition, unless otherwise stated.

[0126] EXAMPLES

[0127] Example 1: Preparation of non-nanometric guanine particles according to the process of the invention

[0128] The initial guanine particles, including nanometric particles, come from the supplier TCI and have a mixture of polymorphic forms: alpha / beta with the distribution ranging from 20 / 80 to 80 / 20.

[0129] Another sample of guanine particles obtained by precipitation and comprising nanometric particles with an alpha / beta polymorphic form (10 / 90 distribution) is used as a negative control.

[0130] There are two possible routes for removing nanometric guanine particles: the acidic route or the basic route. Working in an alkaline (basic) medium has proven easier and yielded a higher rate. However, in both cases, returning to an acceptable pH results in a significant decrease in the crystallinity of the final product and the potential formation of new fine particles. To avoid this problem, the solid is progressively washed sequentially (step (iii)) with aqueous solutions of decreasing base concentration when the polishing step (i) is performed (il) in a basic medium (or alternatively, an aqueous solution of decreasing acid concentration when polishing (i) is performed (i2) in an acidic medium).

[0131] 1-1 Process according to an isothermal batch mode (double-jacketed reactor)

[0132] According to a first method, the non-nanometric guanine particle powder was obtained in a double-jacketed reactor (30g in 300cc of 1M NaOH solution) using an isothermal method.

[0133] The solubility of guanine in 1 M aqueous sodium hydroxide at 20°C is 5.66% (mass fraction). The progressive, multi-stage washing process ensures that no significant loss of crystallinity is observed and also prevents the uncontrolled nucleation of new nanoparticles.

[0134] In total, suspension under stirring in 1 M NaOH at 20°C for 16 hours, followed by sequential washing, resulted in:

[0135] 1. a structurally pure form,

[0136] 2. suppression of fine particles (particles smaller than 100nm), and

[0137] 3. Improved crystallinity.

[0138] 1-1bis Process according to a semi-continuous - continuous isothermal mode (Taylor Couette reactor)

[0139] Alternatively, the non-nanometric guanine particle powder was obtained in a Couette Taylor reactor in an isothermal mode.

[0140] The treatment consists of suspension under stirring (1200 rpm) in 1 M NaOH at 80°C for 15 minutes.

[0141] After filtration through No. 4 sinter, the solid was vigorously washed by resuspension with a 10' aqueous sodium hydroxide solution 5 M, then rinsed with water and led to:

[0142] 1. a structurally pure form and

[0143] 2. suppression of fines (particles smaller than 100nm).

[0144] 1-2 Process according to a mode with temperature cycles ('non-isothermal' mode)

[0145] The 'non-isothermal' mode is achieved with a temperature gradient. This can be spatial, with two reactors regulated at different temperatures and connected to each other, the suspension circulating between the two reactors, as exemplified below. Alternatively, it can be temporal, with a cyclic temperature program as a function of time. According to this example of a non-isothermal mode, non-nanometric guanine particle powder was obtained in a Couette Taylor-type reactor using a temperature cycling mode with several thermostats: outer cylinder jacket 80°C, inner cylinder jacket 70°C. The TCI (Total Carbonate Index) of guanine corresponds to a suspension concentration of 21.33% w / w. Inner cylinder rotation: 1200 rpm.

[0146] After 15 minutes of these continuous, cyclical temperature variations between the two cylinders, the suspension was filtered through a No. 4 glass filter (no loss at the filter, i.e., the filtrate was clear). The solid was vigorously washed by resuspension with an aqueous sodium hydroxide solution for up to 10 minutes. 5 M, then rinsed with water.

[0147] The cycle profile can be amplified and shortened to accelerate maturation, the temperatures of the two cylinders can be modified, and the sodium hydroxide concentration in the polishing stage can also be adjusted up to 1.66M. The sequential washing can also be 'softened' by adding more intermediate stages. It is also possible to achieve this polishing by circulating the suspension between two reactors at different temperatures or with a time-based cyclic program on a single double-jacketed reactor connected to a programmable thermostat with a heat transfer fluid circulation system.

[0148] Example 2: Effect of a basic wash (NaOH 10' 5 M) unique before a water wash, after the polishing step compared to a condition without washes.

[0149] This example consisted of comparing, respectively, the control (TCI guanine) not subjected to the process of the invention, condition A in which the TCI guanine is subjected to the process of the invention comprising a 15-minute polish in a Taylor Couette NaOH (1 N) according to examples 1-1 bis and 1-2 described above before washing, and a comparative condition B in which the TCI supplier's guanine is subjected to a 15-minute polish in a Taylor Couette NaOH (1 N) but with a single intermediate NaOH wash at a concentration of 10⁻¹². 5 M before the final water wash.

[0150] Example 3: Evaluation of the distribution and structure of the guanine particles obtained in example 1-1 bis (Taylor Couette in 'isothermal' mode), as well as their conductivity performance. The characteristics and properties of the guanine particles thus obtained in example 1-1 (isothermal mode) were evaluated, compared to the initial guanine particles comprising nanometric guanine particles containing both alpha and beta forms.

[0151] 3-1 Effect of the process of the invention on the particle size distribution of and the purity of a form

[0152] XRD analyses on powder at room temperature were recorded on a Bruker D8 Discover instrument under the following conditions:

[0153] Analysis range: 3°-40° (2-theta)

[0154] Analysis step size: 0.04°

[0155] Measurement time per step: 1 s

[0156] k-filter (Ni)

[0157] Copper anticathode (Å = 0.15418 nm), 40 kV, 40 mA

[0158] Anti-diffusion knife with low angles

[0159] Data processing: Bruker software [va release 2018 V 4.3.0.1],

[0160] Figure 2 shows that the initial guanine powder from supplier TCI comprises both the alpha and beta forms.

[0161] Figure 3 confirms the pure crystalline 'alpha' form of the guanine particle powder obtained according to example 1-1, and its maintenance of crystallinity during successive washes.

[0162] 3-2- of the

[0163] The morphology and size of the initial guanine particles and the particles obtained according to the process of the invention were observed by Scanning Electron Microscopy (SEM) under the following conditions:

[0164] JEOL brand MEB model JSM 7200F

[0165] Secondary electron imaging mode

[0166] 25x to 100,000x magnification

[0167] Deep empty mode engaged

[0168] Acceleration voltage of 5-20kV

[0169] Sample preparation: the samples were glued onto pads using conductive adhesives and were coated with gold (a few nm) to reduce charge accumulation during observations, using a Bal-Tec SCD500 metallizer. The images are shown in Figures 4a (20000x magnification) and 4b (50000x magnification) for the initial guanine (TCI) (alpha / beta) and in Figures 5a (20000x magnification) and 5b (50000x magnification) for the guanine (alpha) obtained according to the process of the invention (example 1-1 bis isothermal mode), as well as in Figure 6 for the guanine (alpha) obtained according to the process of the invention (example 1-2 non-isothermal mode) (6a: 20000x magnification and 6b: 50000x magnification).

[0170] The following morphological characteristics were observed:

[0171] The edges of the particles (alpha) are smoother than for the initial TCI product (alpha / beta);

[0172] Some surfaces are smooth;

[0173] - Absence of isolated particles below 100 nm.

[0174] 3-3 Evaluation of confidence

[0175] The non-nanometric guanine particle powder obtained according to example 1-1 (isothermal mode) was evaluated for its coverage performance according to the following protocol:

[0176] Preparation of a varnish (nail polish base) with 4% guanine powder in a varnish base;

[0177] The varnish is spread evenly (spreading of 300pm) on a contrast card (for example Leneta 2A) and then dried;

[0178] The dry spread is analyzed by spectrophotometer (MA98, at 45° relative to the specular angle).

[0179] In the results described below, coverage is expressed as a percentage: 100% indicates that there is no color difference between the black and white parts of the contrast card after spreading; then, by comparing the white side and the black side, a % of coverage is obtained.

[0180] The initial guanine sample containing nanoparticles (supplier TCI) (approximately 50% alpha / 50% beta) exhibits 44.3% coverage, while the guanine powder without nanoparticles and solely in the alpha form (100% "alpha") obtained according to the process of the invention exhibits a comparable coverage of 44.4%. These results demonstrate that the guanine powder without nanoparticles and in the single alpha form, obtained according to the process of the invention, exhibits comparable coverage to the initial guanine sample (containing nanoparticles).

[0181] Another coverage test was performed in parallel, following the same protocol, with a guanine sample containing nanoparticles obtained by precipitation (approximately 90% "beta" / 10% "alpha"): a coverage value of 29.8 was obtained, significantly lower than that evaluated with guanine powder without nanoparticles and in the single alpha form (100% alpha). This demonstrates the advantage of enriching a guanine sample in the alpha form, or even obtaining a guanine powder in the single alpha form, to achieve the desired coverage properties. and the structure of obtained in example 1-2 in mode with Thus of their coverage

[0182] The characteristics and properties of the guanine particles thus obtained in example 1-2 (mode with thermal cycles) were evaluated.

[0183] 4-1 Effect of the process of the invention on the qranulometry of and the purity of a form

[0184] The nano or non-nano nature of the guanine powder obtained in example 1-2 is evaluated by scanning electron microscope imaging on several samples.

[0185] XRD powder analyses are performed on the same apparatus as described previously.

[0186] Figure 7 confirms the structural purity of the alpha crystalline form of the guanine particle powder obtained according to Example 1-2, and its maintenance during washing with aqueous sodium hydroxide solution 10' 5 M and the final wash with water.

[0187] The effect is very clear on the particle size distribution, which, moreover, are all of the alpha polymorphic form.

[0188] 4-2- Microscopic analysis of particles The morphology and size of the guanine particles obtained according to the process described in example 1-2, were observed by Scanning Electron Microscopy (SEM), under the conditions described previously.

[0189] Figure 6 illustrates the SEM image of guanine obtained according to the process described in example 1-2 (6a with X20000 magnification, and 6b with X50000 magnification).

[0190] The following morphological characteristics were observed:

[0191] The edges of the guanine particles obtained according to the process described in example 1-2 are smoother than for the initial TCI product;

[0192] Some surfaces are smooth;

[0193] - Absence of isolated particles below 100 nm.

[0194] 4-3 Evaluation of confidence

[0195] The non-nanometric guanine particle powder obtained according to example 1-2 was evaluated for its coverage performance according to the protocol described in the previous example.

[0196] The initial guanine sample in the presence of nanoparticles (supplier TCI) has a coverage of 44.2% and the guanine powder without nanoparticles and only of alpha form obtained according to the process of the invention (1-2) has a comparable coverage of 43.1%.

[0197] These results have therefore shown that the process according to the invention of polishing guanine particles in the presence (i1) of a basic solution or alternatively (i2) of an acidic solution, followed by sequential washes with decreasing base concentration when step (i) is carried out (i1) in a basic medium or sequential washes with decreasing acid concentration when step (i) is carried out (i2) in an acidic medium, followed by rinsing with water, in particular in a Couette-Taylor type reactor, and whether in isothermal mode or in thermal cycle mode, in batch or continuous (semi-continuous), makes it possible to obtain non-nanometric guanine particles, of a unique stable polymorphic "alpha" form and whose coverage properties are consistent with the coverage properties of the initial compound.

[0198] Such non-nanometric guanine particles obtained according to the process of the invention are therefore advantageous and usable in the formulation of cosmetic compositions. 5: Recycling of sodium hydroxide solutions in the process for preparing non-nanometric guanine according to the invention

[0199] The inventors have shown that the 1 M NaOH solution obtained after filtration (“mother liquor”) always contains a non-negligible amount of dissolved guanine (about 66 g / L).

[0200] This example shows the possibility and the interest of recycling this sodium hydroxide solution used saturated with guanine in the process of preparing non-nanometric guanine particles according to the invention.

[0201] The initial guanine particles, including nanometric particles, come from the supplier TCI and have a mixture of polymorphic forms: alpha / beta with the distribution ranging from 20 / 80 to 80 / 20.

[0202] 28.5 g of guanine TCI were mixed for 7 h at room temperature in 100 mL of 1 M NaOH solution saturated with guanine.

[0203] The solid was filtered and collected. It was then washed with 100 mL of 10' NaOH solution 1 M saturated with guanine for 4 h under vigorous stirring and then filtered. The resulting filter cake was rinsed with 50 mL of 10' NaOH 2 M saturated.

[0204] The solid was then washed with 100 mL of 10' NaOH solution 3 M saturated with guanine for 6 h under vigorous stirring and then filtered. The resulting filter cake was rinsed with 50 mL of 10' NaOH 4 M saturated.

[0205] The solid was then washed with 100 mL of 10' NaOH 5 M was stirred vigorously for 4 hours and then filtered. The resulting filter cake was rinsed with 50 mL of NaOH 10- 6 Mr.

[0206] The solid was then washed with 150 mL of water for 3 hours under vigorous stirring and then filtered. The resulting filter cake was rinsed twice with 50 mL of water.

[0207] The solid was placed for 14 hours in a fan-assisted oven at 45°C. The final yield was greater than 99%. This experiment demonstrates that the basic solution has a catalytic effect on the suspension. The industrial process can include the reuse of the NaOH 10' washing solutions. n M (n = 1, 2, 3, 4) saturated in guanine for a quasi-quantitative yield.

[0208] The characteristics and properties of the guanine particles thus obtained were evaluated.

[0209] The XRD analyses on powder at room temperature were recorded on a Bruker D8 Discover instrument under the conditions described in example 3.1 above.

[0210] Figure 8 shows that a pure 'alpha' crystalline form of the guanine particle powder can also be obtained under these conditions.

[0211] Example 6: Preparation of non-nanometric guanine particles according to the process of the invention using an acidic aqueous solution

[0212] The initial guanine particles, including nanometric particles, come from the supplier TCI and have a mixture of polymorphic forms: alpha / beta with the distribution ranging from 20 / 80 to 80 / 20.

[0213] 70 g of guanine TCI were refluxed in 320 mL of H3PO42M for 4 h on two occasions.

[0214] The solid was filtered and resuspended with stirring for 4 hours in 150 mL of 0.5 M H3PO4 at 60°C. The suspension was cooled to room temperature and the solid was filtered again through a No. 3 sintered glass.

[0215] The solid was resuspended in 200 mM water for 10 h at room temperature. The product was then filtered and dried.

[0216] The resulting product was off-white.

[0217] The characteristics and properties of the guanine particles thus obtained were evaluated in comparison to the initial guanine particles, which included nanometric guanine particles containing both alpha and beta forms, and to guanine particles obtained using the process with a basic aqueous solution. X-ray diffraction (XRD) analyses of the powder at room temperature were recorded on a Bruker D8 Discover instrument under the conditions described in Example 3.1 above.

[0218] Figure 9 confirms the pure crystalline form "alpha" of the guanine particle powder obtained according to the process of the invention with an acidic aqueous solution, and its maintenance of crystallinity during washings.

[0219] Figure 10 shows the particle size distribution of the powder at the end of polishing in acidic medium and sequential washing.

[0220] Figure 11 is a zoom on the powder obtained after the acid polishing step and sequential washing.

[0221] These images, compared to Figure 4a, show the production of non-nanometric guanine under these acidic conditions.

[0222] REFERENCES

[0223] Coquerel, G., in The 'structural purity' of molecular solids-An elusive concept? , Chem. Eng. Process 2006, 45, 857-862. MARC, Laureline; Schneider, Jean-Marie; Kim, Woo-Sik; Coquerel, Gérard- A promising solution to ensure Ibuprofen continuous crystallization limiting the encrustation in a Couette- Taylor crystallizer; Journal:, 2024; Industrial & Engineering Chemistry Research 63(38):16462-16471, DOI: 10.1021 / acs.iecr.4c01667

[0224] Birju Shah, Vasu Kakumanu, Arvind K. Bansal; Analytical Techniques for Quantification of Amorphous / Crystalline phases in Pharmaceuticals Solids; Journal of Pharmaceutical Sciences, Vol. 95, No.8, August 2006.

[0225] Ilhan llzun, Methods of determining the degree of crystallinity of polymers with X-ray diffraction: a review. Journal of Polymers Research (2023) 30:394.

[0226] Bowen Zhang, Gerard Coquerel, Jinsoo Kim, Bum Jun Park, Woo-Sik Kim- Deracemization of Sodium Chlorate by Hydrodynamic Attrition of Taylor Vortex Flow; Separation and Purification Technology; Separation and Purification Technology 354 (2025) 128700, On line access : https: / / doi.Org / 10.1016 / j.seppur.2024.128700.

Claims

TJ DEMANDS 1. A process for preparing, by physico-chemical polishing, a powder of non-nanometric guanine particles, all of whose particle dimensions have a minimum size greater than 100 nm and of a unique polymorphic "alpha" shape, characterized in that the process comprises the following steps: (I) suspension of guanine particles (11) in a basic aqueous solution or alternatively (12) in an acidic solution, the concentrations of base or alternatively of acid being lower than the concentrations allowing the formation of guanine salts, (II) filtration and recovery of said particles, (III) sequential washing of said particles with aqueous solutions of decreasing base concentration when step (i) is carried out (ii) in a basic medium or alternatively with aqueous solutions of decreasing acid concentration when step (i) is carried out (ii2) in an acidic medium, followed by rinsing with water, and (IV) recovery, in particular by filtration, of a powder of non-nanometric guanine particles and of unique polymorphic form "alpha".

2. The method according to claim 1, characterized in that it is carried out in a double-jacketed reactor, and in particular with the following conditions: Temperature: from 20°C to 95°C; Duration: from 5 minutes to 20 hours; and Concentration of acid or base of the solution used for step (i) which is less than the concentration allowing the formation of guanine salts.

3. A process according to one of claims 1 or 2, characterized in that step (i) is carried out in batch or continuous (semi-continuous) mode.

4. Batch process according to claim 3, characterized in that the solution obtained in step (i) is reused as a catalyst in another batch, to treat new guanine particles according to the same process.

5. A process according to any one of claims 1 to 4, characterized in that the basic solution comprises a base selected from: NaOH, Na2CO3, K2CO3, KOH, NH4OH, Ca(OH)2, and mixtures thereof, at a concentration lower than the concentration required to form guanine salts, preferably NaOH, at a concentration ranging in particular from 0.1 M to 1.66 M for the basic solution of step (i), and at decreasing base concentrations down to 10' 5 M for the basic solutions of step (iii).

6. A process according to claim 5, wherein step (i) comprises suspending the guanine powder, under stirring, in a 1 M NaOH basic solution, at a temperature of 20°C for a period of 5 minutes to 20 hours.

7. A process according to any one of claims 1 to 4, characterized in that the acid solution comprises an acid selected from HCl, H2SO4, H3PO4, HNO3, HCI4, and mixtures thereof, at a concentration lower than the concentration required to form guanine salts, preferably H3PO4, at a concentration ranging in particular from 0.2 M to 2.0 M for the acid solution of step (i), and at decreasing acid concentrations down to 10' 5 M for acidic solutions from step (iii).

8. A method according to any one of claims 1 to 7, characterized in that step (i) is carried out at isothermal temperature or alternatively with cyclic temperature variations.

9. Powder of non-nanometric guanine particles having all particle dimensions a minimum size greater than 100 nm obtained according to the preparation process defined in any one of claims 1 to 8.

10. Powder of non-nanometric guanine particles, characterized in that all particle dimensions have a minimum size greater than 100nm and in that it is of unique polymorphic shape 'alpha', comprising particles of shape 'alpha' and less than 5% by weight, or even less than 1% by weight of particles of shape 'beta', or is free of particles of shape 'beta'.

11. Cosmetic composition comprising, in a physiologically acceptable medium, a powder of non-nanometric guanine particles, all of whose particle dimensions have a minimum size greater than 100nm as defined in claim 9 or claim 10, and at least one additional cosmetic ingredient.

12. Cosmetic process for the care and / or makeup of keratinous materials comprising the application to said keratinous materials of a cosmetic composition as defined in claim 11.

Images