JP2006225392A - Cross-linked polymer of carbohydrate - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To produce an active ingredient which is based on various proteins or peptides, does not have the problem of allergy facing on the employment of such the substances, and has a tightening effect, and furthermore to produce a cross-linked polymer of a carbohydrate. <P>SOLUTION: This cross-linked polymer uses at least one carbohydrate having at least one primary alcohol functional group. This polymer can be used for producing compositions intended to be coated on the skins to obtain effects for tightening and/or arranging the skins. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to the production of active ingredients which are based on various protein or peptide substances, but without the problems of allergies encountered when such substances are used and which have a tensing effect. The invention further relates to producing a crosslinked polymer of carbohydrates.

  Cosmetic formulations very often contain substances that can induce a characteristic tightening effect. Such an effect can improve recognition of the effectiveness of cosmetic preparations, especially due to the perceptual effect noticed significantly by consumers.

  Moreover, such a tightening effect, on the one hand, temporarily reduces skin wrinkles, but on the other hand, when used in preparations around the eyes, neck, neckline or hand type, Can tighten.

  The substances best known to have such properties are, inter alia, bovine serum albumin or collagen, which are the molecules most frequently used before. More recently, substances developed for the purpose of such activity have turned to plant source materials, and in particular, plant proteins have become widely used for such activity purposes. .

  Thus, for example, the plant albumin fraction of cereals or legumes was the subject of a patent of particular interest as an analog of bovine serum albumin (Patent Document 1). Polymerization of plant proteins with the aid of bifunctional agents has also been described for various cosmetic purposes (Patent Documents 2 and 3). In addition, substances made by polymerizing fractions obtained by subjecting plant proteins to hydrolysis have been described and used for the purpose of tightening with cosmetics (Patent Document 4).

  However, the use of proteins in cosmetics has become a problem because proteins can induce immune responses with varying strengths and can even induce allergies that cannot be tolerated at all. Some examples of proteins well known to those skilled in the art to cause such immune responses are proteins derived from wheat, nuts, hazelnuts, peanuts, and milk.

  It should be taken into account that the use of skin irritating compounds, such as proteins, in cosmetics may be restricted or prohibited by law in the future.

A special solution that will allow engineers in the field to alleviate the problem that certain compounds that can be used in cosmetics or drugs for the purpose of tightening effects can also cause irritation Is not described in the prior art.
WO94 / 18944 FR 2,766,090 (corresponding to US Pat. No. 5,912,016) FR 2,780,901 (corresponding to US Pat. No. 6,197,757) WO 03/040216 A1

  The main object of the present invention is to solve such a new technical problem, which allows the user to obtain the effect of tightening and / or trimming the skin surface in a perceptible manner. Providing compounds that do not induce any possible allergic reactions.

  One object of the present invention is a toning solution [which preferably exhibits excellent biocompatibility, complete biodegradability, complete anabolism, is completely harmless. And is based on starting materials that can be found not only in the animal kingdom but also in the plant kingdom and can also be produced by microbial fermentation]. Is to solve various technical problems.

  One object of the present invention is also to solve the technical problem by providing a novel process for the preparation of compounds which makes it possible to solve the technical problems listed above.

  It is the first time that all such technical problems are solved in a manner that can be used inexpensively and on an industrial scale, notably in a cosmetic scale, in a satisfactory manner.

  The inventors have found in a surprising manner that a cross-linked polymer of at least one carbohydrate or carbohydrate derivative can be used on skin tissue, such as human skin, to obtain an effect of tightening and / or conditioning it. .

  Accordingly, the present invention relates to a crosslinked polymer of at least one carbohydrate containing at least one primary alcohol functional group according to the first aspect, and in particular, a crosslinked polymer obtainable according to the method defined below. About. If the polymer of at least one carbohydrate containing at least one primary alcohol functional group is in the form of a capsule or sphere, in particular in the form of a microcapsule or microsphere, or in the form of a nanocapsule or nanosphere, Such polymers are excluded from the present polymer.

  The present invention relates to a cosmetic and / or skin-drug and / or pharmaceutical composition comprising a cross-linked polymer as defined above according to a second aspect.

  The present invention also provides a composition according to the third aspect intended to obtain an effect of tightening and / or conditioning said tissue by applying a cross-linked polymer as defined above to the skin tissue of a subject. Also related to use in

  The term “carbohydrate” as used herein means not only carbohydrates but also carbohydrate derivatives containing at least one or more primary alcohol functions.

  Within the context of the present invention, the effect of tightening and / or trimming mainly does not cross-link the viscosity of the applicant's opinion and / or skin roughness measurement and / or the aqueous solution of the cross-linked carbohydrate. It is the effect measured by comparing with an aqueous solution of carbohydrates.

  The present invention, according to one variant, relates to the use of the crosslinked polymer in the manufacture of a composition intended to be applied to the skin tissue of a subject to obtain a reduction in said tissue wrinkles and / or small wrinkles.

  The present invention, according to another variant, relates to the use of the crosslinked polymer in the manufacture of a composition intended to apply to the skin tissue of a subject to improve the biomechanical properties of the tissue.

  The composition is advantageously a cosmetic, dermopharmaceutical or pharmaceutical composition intended to be applied to at least part of the face, in particular around the eyes and / or neck and / or hands and / or neckline and / or chest. is there.

  The product derived from the present invention exhibits the effect of conditioning the skin when a composition containing it is applied. The product derived from the present invention does not have any effect that it causes any appreciable allergy when such a composition is applied to the skin.

  The product of the present invention is adsorbed on the surface of the skin to form a smooth and continuous elastic membrane. Thus, of particular interest are the filmogenic, tightening and plasticizing properties that carbohydrates, notably polysaccharides and / or oligosaccharides and / or polyols, exhibit when they are so polymerized. .

  Accordingly, the product of the present invention advantageously has film-forming and / or plasticizing properties.

  Such carbohydrate is preferably selected from any one of polysaccharides, oligosaccharides, polyols and / or mixtures thereof.

  The present invention, according to a fourth aspect, relates to a method of cosmetic care, which comprises topically applying a composition as defined above.

  Applicants are aware of a method of polymerizing polysaccharides or oligosaccharides (COLETICA FR 2,688,422, US Pat. No. 5,562,924). However, such a process is an emulsion interfacial polymerization process suitable for producing microcapsules and producing microspheres. Thus, using such a method, high molecular weight polymers of carbohydrates cannot be obtained in forms other than sphere and / or capsule form, particularly in neither microcapsule nor microsphere form.

  Therefore, according to the fifth aspect, the present invention describes a method for producing a crosslinked polymer, which comprises a crosslinking reaction between a primary alcohol functional group possessed by a carbohydrate and a reactive functional group possessed by a crosslinking agent. Causing in a homogeneous aqueous phase to obtain a crosslinked polymer of at least one carbohydrate.

  Such carbohydrates are preferably selected from any one of polysaccharides, oligosaccharides, polyols and mixtures thereof.

  The molecular weight of the carbohydrates in the first embodiment, in particular polyols and / or oligosaccharides, is equal to or greater than 150 grams per mole (shown as g / mol or Dalton, ie Da in the rest of the context), preferred Is equal to or greater than 2,000 Da.

  In this first embodiment, the molar ratio of carbohydrates, in particular polyols and / or oligosaccharides to crosslinker is advantageously greater than or equal to 0.1, preferably equal to or greater than 1.

The molecular weight of the carbohydrate, in particular the polysaccharide, in the second embodiment is equal to or greater than 50,000 Da, preferably equal to or greater than 100,000 Da, more preferably 300.
Equal to or greater than 1,000 Da. In this case, hydrolysis may be carried out prior to the crosslinking reaction so that a mainly soluble polymer can be produced by the polymerization reaction. Methods for subjecting carbohydrates to hydrolysis are known to those skilled in the art.

  In this second embodiment, advantageously, the molar ratio of carbohydrate, in particular polysaccharide, to crosslinking agent is less than 0.1, preferably less than 0.01.

Such polysaccharides preferably have a primary alcohol function as a diosidic moiety.
moiety) 0.5 to 4 per one.

  Advantageously, before reacting such a carbohydrate, it is mixed with excipients that are acceptable by the topical route, in particular cosmetically or dermatologically acceptable excipients.

  According to another special embodiment variant, the concentration of carbohydrates with primary alcohol functionality, notably polysaccharides and / or oligosaccharides and / or polyols, is from 0.001% to 50% by weight of the aqueous phase, more Specially within the range of 0.1 to 10% by weight.

  Said cross-linking agent is preferably a polyfunctional cross-linking agent, i.e. a cross-linking agent containing at least two reactive functional groups which can mainly react with the primary alcohol functional groups of the carbohydrate, which is preferably polycarboxylic acid It is selected from any one of chloride, carboxylic anhydride, polyisocyanate, polythioisocyanate, polyaldehyde and mixtures thereof.

  If such a carbohydrate is in the high molecular weight range, it is preferred to subject it to hydrolysis in a homogeneous aqueous phase and then contact it with a crosslinker prior to reacting it.

  The method advantageously comprises removing the compound insoluble in the aqueous phase after the crosslinking reaction if insoluble compounds are present at the end of the reaction.

  In a particular embodiment, the method comprises dissolving the carbohydrate in an aqueous phase and then adding it to a phase containing a cross-linking agent, which can be dissolved or insoluble in alcohols such as ethanol and / or butylene glycol. It comprises the formation of a crosslinked polymer of carbohydrates, notably a high molecular weight polymer, in contact for a time sufficient to obtain carbohydrate crosslinking.

  As explained in the above paragraph, the inventors obtained high molecular weight polymers by polymerizing carbohydrates in a homogeneous aqueous phase. This method is extremely advantageous from the viewpoint of industrial production because the number of reaction steps is limited, the cost of starting materials is limited and the safety of workers is maintained.

  It was unexpected that the resulting polymer had a property known as the “tightening effect” property.

  The invention is particularly notable for crosslinking crosslinked carbohydrates such as polysaccharides and / or oligosaccharides and / or polyols, preferably with the aid of multifunctional agents known to those skilled in the art. Relates to the use of carbohydrates crosslinked by crosslinking with their primary alcohol functionality.

The present invention relates to a process for producing high molecular weight polymers (or cross-linked products) of carbohydrates, notably polysaccharides and / or oligosaccharides and / or polyols containing primary alcohol functional groups, The following sequential steps:
1) dissolving a material rich in carbohydrates, notably polysaccharides and / or oligosaccharides and / or polyols, in an aqueous phase;
2) Add the multifunctional agent (crosslinking agent) selected as described above to polymerize the carbohydrate,
3) optionally removing insoluble (insoluble) reaction products from the reaction medium,
Comprising the steps of:

  Using the process of the present invention, a carbohydrate of interest, notably a carbohydrate of interest in cosmetics, notably a polysaccharide and / or oligosaccharide and / or polyol polymer (crosslinked) is produced. be able to. The carbohydrate polymer thus obtained has a high molecular weight and surprisingly exhibits full skin tolerance.

  One of the advantages of the method of the present invention is that high molecular weight molecular structures (inducing improved biomechanical properties of the skin) from materials rich in carbohydrates, ie polysaccharides and / or oligosaccharides and / or polyols. Can create a three-dimensional network that can be generated).

  It is not easy to define a cross-linked polymer according to the invention in a clear manner, because it is impossible to identify the degree of cross-linking. As will be explained, the term “high molecular weight polymer” as used by the inventors means that a significant percentage of the chain has a molecular weight equal to or greater than 50,000 daltons, especially to crosslink polysaccharides. Preferably means a polymer having a molecular weight equal to or greater than 150,000 daltons, more preferably equal to or greater than 300,000 daltons.

Other additional or alternative features of the method of the invention are the following:
The material rich in carbohydrates, notably polysaccharides and / or oligosaccharides and / or polyols, is preferably selected from natural sources of plant and / or animal sources and / or biotechnological sources (eg fermentation) To do.
The material is dissolved in the water phase at a rate of 20 g / l to 500 g / l.

According to a particular embodiment, the polysaccharides and / or oligosaccharides and / or polyols having the primary alcohol functional groups listed above are selected from the group consisting of:
The following polysaccharides:
-Galactomannans, such as galactomannans derived from guar, such as Viscogum (TM) (SANOFI), or galactomannans derived from carob beans, such as Lygomme (TM) (SANOFI) or MeyproFlure (TM) or Meyprodyn (TM) ( Commercially available galactomannans under the name MEYHALL);
-Carrageenans, eg carrageenans extracted from red algae, eg carrageenans commercially available under the name Satiagel ™ or Satiagum ™ (DEGUSSA) or Genvisco ™ (HERCULES);
-Glucomannan, for example glucomannan derived from konjac gum, such as glucomannan commercially available under the name Nutricol (TM) (FMC Corporation) or Propol (TM) (FMC SCHIITZU);
A polysaccharide having primary alcohol functional groups derived from fermentation, such as xanthan (KELKO), Gallane ™ (KELKO), Curdlane ™ (TAKEDA) or hyaluronic acid;
-Cellulose, such as Natrosol ™ 250HHX (AQUALON), Klucel EF ™ (AQUALON), Vivapur ™ (Instel)
Chimos);
-Cellulose derivatives such as hydroxypropylmethylcellulose (Aqualon), methylethylcellulose (Aqualon), methylhydroxymethylcellulose (Aqualon) or Blanose (TM) (Aqualon);
-Polyholosides, such as Dextran (TM), Dextran T70, T500 or T2000, Dextran sulfate (Pharmacia Fine Chemicals);
-Agar, eg food quality agar (Sigma), bacteriological agar (Setexam), Monogar M540 Agar (Setexam) or Agar QSN5 (Setexam);
An alginate, for example the sodium salt of alginic acid A2158 (Sigma), Satialgine ™ (Degussa) or sodium alginate FD 125 (Danisco);
-Derived from starch, eg amylopectin (Fluka), amylose (Fluka), Nastar ™ (Coscula), Waxy Maize starch (Roquette), Waxillis ™ (Roquette), starch derived from wheat (Roquette), rice Starch (Roquette), potato-derived starch (Roquette) or corn-derived starch (Roquette);
-Chitosan, such as Kitamer (TM) (Unipex);
A curdlan, eg Pureglucan ™ (Takeda);
-Gum adragante or gum tragacanth (Emiga);
-Gum arabic or gum acacia (Colin) or Valgum (TM) (Valmar);
-Chia gum (Sigma);
-Elemi rubber (Emiga);
-Gellan gum, such as Kelcogel ™ (SPCI);
-Gum gati or Indian Gum (Sigma);
-Karaya gum (Sigma);
-Shellac (Sigma);
-Manila rubber (Sigma);
Examples of the following oligosaccharides, monosaccharides or disaccharides (commercially available from Sigma unless otherwise specified):
-Cyclodextrins (especially alpha, beta or gamma cyclodextrins or their derivatives);
Dextrin (Glucidex 40 ™ or Glucidex 47 ™, Roquette);
-Raffinose, cellobiose, sucrose, maltose, lactose, trehalose, dihydroxyacetone (DHA), fructose, sorbose, ribose, deoxyribose, xylose, arabinose, glucose, mannose, galactose, erythrose, threose, allose, atrose, gulose, idose , Talose, erythrulose, xylulose, psicose, tagatose, cedoheptulose, xylobiose, chitobiose, nigerose, aminaribiose, kojibiose, sophorose, gentianse (gentiose) se), turanose, stachyose, bell bus course (verbascose);
-Gluconic acid, gluconolactone, glucosamine, galactosamine, galactosamine sulfate, glucosamine sulfate;
-Saponins, for example saponins from the bark of quilla;
-Guanosine, uridine;
-Streptomycin sulfate;
-Riboflavin; and the following polyols shown as examples: (commercially available from Roquette unless otherwise specified):
Glycerol, sorbitol, erythritol (Sigma), maltitol, sorbitol, mannitol, lactitol (Sigma), galactitol (Sigma), ribitol (Sigma), glycerol (Sigma), xylitol, myo -Inositol, polyethylene glycol, or PEG with a certain molecular mass and thus with different degrees of polymerization.

  According to a special embodiment, the polysaccharides and / or oligosaccharides and / or polyols having the primary alcohol functional groups described above are preferably polysaccharides derived from xanthan, cellulose, carob beans, xylitol, maltose, carrageenan , Raffinose, acacia gum, mixture of glycerol (eg 10% w / w) and xanthan (eg 2% w / w), mannitol (eg 10% w / w) and inulin (eg 5% w / w) ) And any one of these mixtures, which are preferably cross-linked using sebacic acid dichloride or terephthalic acid dichloride.

  According to a special embodiment, xanthan which crosslinks polysaccharides and / or oligosaccharides and / or polyols having primary alcohol functional groups as described above preferably with sebacic acid dichloride, cellulose which is crosslinked with sebacic acid dichloride, Rubber derived from carob beans cross-linked with sebacic acid dichloride, xylitol cross-linked with sebacic acid dichloride, maltose cross-linked with sebacic acid dichloride, carrageenan cross-linked with terephthalic acid dichloride, terephthalic acid dichloride used Cross-linked raffinose, acacia rubber cross-linked with terephthalic acid dichloride, glycerol cross-linked with terephthalic acid dichloride (eg 10%, weight / weight) and xanthan (eg 2%, A mixture of mannitol (eg, 10%, weight / weight) and inulin (eg, 5%, weight / weight) and any one of these mixtures that are crosslinked using terephthalic acid dichloride. Select from the group consisting of polysaccharides.

  According to an advantageous embodiment, the production method comprises a carbohydrate having a primary alcohol function, notably polysaccharides and / or oligosaccharides and / or polyols, which are dissolved in the aqueous phase and then contain the carbohydrates. The aqueous phase is cross-linking agent (which has a functional group that can react preferentially with the primary alcohol function of the carbohydrate and is soluble or insoluble in alcohols such as ethanol and / or butylene glycol, notably Is sufficient to provide a high molecular weight carbohydrate polymer by polymerizing between the primary alcohol functional group of the carbohydrate and the reactive functional group of the cross-linking agent. It is characterized by being conducted for hours.

  According to one embodiment, which is a variant of the process according to the invention, such a crosslinking agent is any one of poly (acid chloride), poly (anhydride), polyisocyanate, polythioisocyanate, polyaldehyde and mixtures thereof. Select from the group consisting of Advantageously, a cross-linking agent is selected that has a non-reactive portion that the skin can tolerate so that the separation operation does not have to be performed after neutralizing the reactants.

  For example, such poly (acid chloride) is selected from acid trichloride and acid dichloride so that it forms an ester bond.

  Advantageously, the weight ratio at which such crosslinkers dissolve in the alcohol generally varies from 5 to 30%, but preferably from 10 to 20%.

  According to preferred features, such cross-linking agents are selected from phthalic acid trichloride, phthalic acid dichloride, sebacic acid dichloride, azelaic acid dichloride, succinic acid dichloride, tricarboxylic acids such as dichloride or trichloride such as citric acid. The poly (acid anhydride) is, for example, an acid dianhydride, such as succinic dianhydride or maleic dianhydride.

  The aqueous phase according to another particularly advantageous embodiment of the process according to the invention is an aqueous alkaline phase, ie an aqueous phase whose pH is alkaline and therefore has a pH greater than 7. A preferred pH range is a pH in the range of about 7.1 to about 10. A more preferred pH is in the range of 8 to 10, preferably 8 to 9. A strong base such as KOH or NaOH, or a weak base such as ammonia solution, borate, phosphate or carbonate may be used as the base that brings the aqueous phase to a basic pH.

  The crosslinked polymers of carbohydrates according to the present invention are prepared in the form of topical compositions, notably cosmetics, skin-drugs or pharmaceutical compositions. From this, excipients for such compositions include, for example, preservatives, softeners, emulsifiers, surfactants, humectants, thickeners, conditioners, matifying agents, stabilizers, At least one compound selected from the group consisting of antioxidants, texture agents, whitening agents, film forming agents, solubilizers, pigments, dyes, fragrances and solar filters is included. Such excipients are preferably amino acids and their derivatives, polyglycerol, cellulose esters, polymers and derivatives, lanolin derivatives, phospholipids, lactoferrin, lactoperoxidase, sucrose-based stabilizers, vitamin E And derivatives thereof, natural and synthetic waxes, vegetable oils, triglycerides, insaponifiables, plant sterols, plant esters, silicon and derivatives thereof, protein hydrolysates, jojoba oil and derivatives thereof, fat-soluble / water-soluble Selected from the group consisting of esters, betaines, aminoxides, plant extracts, esters of sucrose, titanium dioxide, glycine and parabens, more preferably butylene glycol, steareth-2, steareth-21 Glycol-15 stearyl ether, cetearyl alcohol, phenoxyethanol, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, butylene glycol, natural tocopherol, glycerol, sodium dihydroxycetyl, isopropyl hydroxycetyl ether, glycol stearate, triisononaoine ), Octyl cocoate, polyacrylamide, isoparaffin, laureth-7, carbomer, propylene glycol, glycerol, bisabolol, dimethicone, sodium hydroxide, PEG 30-dipolyhydroxystearate, capric acid / caprylic acid triglyceride, cetearyl octanoate, Dibutyl adipate, grape seed oil, jojoba oil, magnesium sulfate Cium, EDTA, cyclomethicone, xanthan gum, citric acid, sodium lauryl sulfate, mineral wax and oil, isostearyl isostearate, propylene glycol dipelargonate, propylene glycol isostearate, PEG 8 beeswax, hydrogenated coconut heart oil (palm tree heart oil) glycerides, hydrogenated coconut oil glycerides, lanolin oil, sesame oil, cetyl lactate, lanolin alcohol, castor oil, titanium dioxide, lactose, sucrose, low density polyethylene and isotonic saline.

The composition described above is preferably a solution (which is an aqueous or oil solution), cream or aqueous gel or oily gel, notably in a pot or tube form, notable shower gel, shampoo, milk , Emulsions, microemulsions or nanoemulsions (which are noteworthy oil-in-water or water-in-oil or multiple or silicon containing), lotions, noteworthy lotions in glass bottles, plastic bottles, measuring bottles , Aerosols, ampoules, liquid soaps, dermatological bars, ointments, foams and anhydrous products (preferably in liquid, pasty or solid form, eg stick form, noteworthy lipstick form) etc. Formulate into a form selected from

  Other objects, features and advantages of the present invention will clearly occur to those skilled in the art when read with reference to the present examples, which are given by way of illustration only and are not intended to limit the scope of the invention in any way. Will.

  This embodiment constitutes an integral part of the present invention and any feature that appears to be novel compared to any state-of-the-art by interpreting the entire description encompassing this embodiment is the function and generality of this embodiment. This constitutes an integral part of the present invention.

  Accordingly, the range of all the examples is a general range.

Moreover, in this example, all percentages are by weight unless otherwise specified, temperatures are expressed in degrees Celsius unless otherwise specified, and pressures are atmospheric unless otherwise specified.
Example

Cross-linking of a 2% aqueous solution of xanthan, demonstrating the tightening effect shown on human skin A preparation of the polysaccharide xanthan (5,000,000 Da) is prepared as follows: 2.10 g of xanthan (KELTROL, SPCI) is dissolved in 93.1 g of cold demineralized water. Next, 4.8 g of NaHCO ₃ is added to the blend under vigorous stirring. After complete dissolution, the pH is stabilized to a value in the range of 8 to 8.4.
2. Preparation of crosslinking agent: 0.75 g of sebacic acid dichloride is dissolved in 4.25 g of butylene glycol.
3. Crosslinking of aqueous xanthan solution: 2. 1. Prepare the solution prepared in 1. Add under stirring to the solution prepared in. The whole is left under stirring for 60 minutes to cause polymerization between the alcohol function of one activated diacid and the other polysaccharide. The reaction is promoted by making the medium basic. After the reaction, a solution containing a crosslinked xanthan can be used as it is, but it contains an insoluble substance. Such insoluble matter may be removed by filtering the product, for example, using a device having a cutoff threshold of 0.22 μm.
4). Principle of measuring the tightening effect: “Video” is mainly used for the purpose of characterizing the cosmetic effect exhibited by the product produced by polymerizing the polysaccharide in the present invention on the biomechanical properties of the skin.
The effect of tightening is measured using a device sold under the trademark Digitizer ™ (Courage et Kazaka). With such a device, a skin roughness variable can be measured, which is measured by the appearance of skin relief images in the form of “ridges and valleys”. The tightening effect increases as the roughness decreases. Two measurement areas (2 cm × 2 cm) are determined on the forearm, and 3. 50 mg of the solution prepared in (1) is applied. Apply 50 mg of uncrosslinked xanthan solution to the second region. After leaving to dry for 1 minute, the volume variable is measured using a “Video Digitizer ™”. The measurement is repeated 10 times for the purpose of improving the uniformity of the measurement. The tightening effect induces a reduction in roughness as measured after treatment. The results are shown in the following table:
Roughness measured with Video Digitizer ™
Unpolymerized solution Before polymerized solution application 64.22 ± 1.56 76.80 ± 0.83
5 minutes after application 64.20 ± 1.56 61.20 ± 1.24
Roughness reduction, ie 0% 20.3%
Tightening effect (%)
This test shows that a significant tightening effect can be obtained when the product of the present invention is applied to the skin of a healthy volunteer.

Crosslinking of a 2% aqueous solution of xanthan 1% trisodium citrate is added to a 2% xanthan solution during stage 1 of Example 1. All other steps are the same. The tightening effect is close to the effect obtained in Example 1.

Crosslinking of 2% aqueous solution of xanthan 0.4% of (tris [hydroxymethyl] aminomethane) is added to the 2% xanthan solution during stage 1 of Example 1. All other steps are the same. The tightening effect is close to the effect obtained in Example 1.

Cross-linking of 2% aqueous solution of xanthan 0.5% of disodium phosphate is added to 2% xanthan solution during stage 1 of Example 1. All other steps are the same. The tightening effect is close to the effect obtained in Example 1.

Crosslinking of cellulose aqueous solution and sensory evaluation An aqueous solution of cellulose (1,000,000 Da) is prepared as follows: 0.56 g of Natrosol ™ 250HHX is dissolved in 94.64 g of cold demineralized water. Next, 4.8 g of NaHCO ₃ is added to the blend under vigorous stirring. After complete dissolution, the pH is stabilized to a value in the range of 8 to 8.4.
2. Preparation of crosslinking agent: 1.5 g of sebacic acid dichloride is dissolved in 8.5 g of butylene glycol.
3. Crosslinking of aqueous cellulose solution: 2. 1. Prepare the solution prepared in 1. Add under stirring to the solution prepared in. The whole is left under stirring for 60 minutes to cause polymerization between the alcohol function of one activated diacid and the other polysaccharide. The reaction is promoted by making the medium basic. After the reaction, a solution containing a cross-linked product of Natrosol ™ 250HHX can be used as it is.
4). Principle for measuring the tightening effect: Two measurement areas (2 cm × 2 cm) are determined on the forearm, and 50 mg of a solution containing a cross-linked Natrosol ™ 250HHX is applied to the first area. Apply 50 mg of uncrosslinked Natrosol ™ 250HHX solution to the second area.

After leaving to dry for 1 minute, the sense of preparation is evaluated by sensory evaluation by a group of volunteers. Sensory evaluation for human skin Uncrosslinked Natrosol Crosslinked Natrosol
(Trademark) 250HHX solution (trademark) 250HHX solution
+++++
+: The effect of tightening was not significantly felt. +++: The effect of tightening was felt very significantly. By this test, when the product of the present invention was applied to the skin of a healthy volunteer, a significant tightening effect could be obtained. This can be detected by sensory evaluation.

Cross-linking of an aqueous solution of carob bean gum (300,000 Da) During step 1 of Example 5, a 5% solution of carob beans, preferably a 2% solution of carob beans, is prepared. All other steps are the same. The tightening effect is close to the effect obtained in Example 5.

Crosslinking of aqueous xylitol (152 Da) A 5% solution of xylitol is prepared during step 1 of Example 5. All other steps are the same. The tightening effect is close to the effect obtained in Example 5.

Crosslinking of aqueous maltose (342 Da) solution During stage 1 of Example 5, a 20% solution of maltose is prepared. All other steps are the same. The tightening effect is close to the effect obtained in Example 5.

Example 9a
Cross-linking and fluidity modification of carrageenan aqueous solution An aqueous solution of carrageenan (500,000 Da) (Genuvisco ™, HERCULES) is prepared as follows: 0.55 g of Genuvisco ™ (HERCULES) is placed in 94.65 g of cold demineralized water. Next, 4.8 g of NaHCO ₃ is added to the blend under vigorous stirring. After complete dissolution, the pH is stabilized to a value in the range of 8 to 8.4.
2. Preparation of crosslinking agent: 0.1 g of terephthalic acid dichloride is dissolved in 0.9 g of ethanol.
3. Cross-linking of carrageenan aqueous solution: 2. 1. Prepare the solution prepared in 1. Add to the aqueous solution prepared in. The whole is left under stirring for 60 minutes to cause polymerization between the alcohol function of one activated diacid and the other polysaccharide. The reaction is promoted by making the medium basic. After the reaction, the solution containing the carrageenan crosslinked product may be used as it is, or may be filtered for the purpose of removing insoluble compounds.

The effect of tightening is close to the effect obtained in Example 5.
Principle of viscosity measurement: Viscosity measurement is carried out by comparing the viscosity of an aqueous solution of a crosslinked polysaccharide with the viscosity of an aqueous solution of an uncrosslinked polysaccharide. The viscometer used is a Brookfield RVTDV-II rotating device, which is used at speed 50 and needle 04.

Moreover, polymerizing carbohydrates induces an increase in molecular mass, thereby inducing an increase in viscosity that it exhibits in the dissolution medium. The degree of polymerization can be measured by such a viscosity increase test.
Viscosity measurement Uncrosslinked carrageenan solution Crosslinked carrageenan solution 588 cps 2632 cps
(Example 9b)
Crosslinking of an aqueous carrageenan solution that has been previously hydrolyzed 1. Preparation of an aqueous solution of carrageenan (Genuvisco ™, HERCULES) hydrolyzate is carried out as follows: 10 g of Genuvisco ™ (HERCULES) is placed in 90 g of 0.1 M HCl solution (0.1 mol / l). The hydrolysis is carried out for 5 hours at 60 ° C. with gentle stirring and then stopped by neutralization by using 1 M NaOH to bring the pH to the range 8-9.
2. Preparation of crosslinking agent: 0.1 g of terephthalic acid dichloride is dissolved in 0.9 g of ethanol.
3. Cross-linking of carrageenan aqueous solution: 2. 1. Prepare the solution prepared in 1. Add to the aqueous solution prepared in. The whole is left under stirring for 60 minutes to cause polymerization between the alcohol function of one activated diacid and the other polysaccharide. The reaction is promoted by making the medium basic. After the reaction, the solution containing the cross-linked carrageenan is subjected to diafiltration to remove salts, and then filtered for the purpose of removing insoluble compounds, or may be used as it is.

  The effect of tightening is greater than the effect observed in the example shown above (particularly greater than the effect obtained when using the product of Example 5).

Crosslinking of an aqueous solution of raffinose pentahydrate (594 Da) A 10% solution of raffinose is prepared during stage 1 of Example 9. All other steps are the same. Although the tightening effect is close to that obtained in Example 5, the panelists detected a very clear softening effect.

Crosslinking of Acacia Gum Aqueous Solution During step 1 of Example 9, a 5% solution of acacia gum (250,000 Da) is prepared. All other steps are the same. The tightening effect is greater than the effect obtained in Example 5.

Crosslinking of an aqueous solution of polysaccharide / polyol mixture A solution of glycerol (92 Da) (10%, weight / weight) and xanthan (2%, weight / weight) is prepared during Stage 1 of Example 9. All other steps are the same. Although the tightening effect is close to that obtained in Example 5, the panelists detected a very clear softening effect.

Crosslinking of an aqueous solution of an oligosaccharide / polyol mixture During Step 1 of Example 9, a solution of mannitol (182 Da) (10%, weight / weight) and inulin (about 5000 Da) (5%, weight / weight) is prepared. All other steps are the same. Although the tightening effect is close to that obtained in Example 5, the panelists detected a very clear softening effect.

Use of the product of the invention in an oil-in-water emulsion type cosmetic or pharmaceutical formulation 14a:
A Water 100 (Qsp)
Butylene glycol 2
Glycerin 3
Sodium dihydroxycetyl phosphate 2
Isopropyl hydroxycetyl ether
B Glycol stearate SE 14
Triisononaoin 5
Octyl cocoate 6
C butylene glycol, 2
Methylparaben,
Ethylparaben, propylparaben pH adjusted to 5.5 D Product of the invention 0.01-10%
Formula 14b:
A Water Amount to be 100 Butylene glycol 2
Glycerin 3
Polyacrylamide, isoparaffin, 2.8
Laureth-7
B Butylene glycol, 2
Methylparaben,
Ethylparaben, propylparaben, phenoxyethanol, 2
Methylparaben,
Propylparaben, Butylparaben Ethylparaben Butylene glycol 0.5
D Product of the invention 0.01-10%
Formula 14c:
A Carbomer 0.50
Propylene glycol 3
Glycerol 5
Amount of water to be 100 B Octyl cocoate 5
Bisabolol 0.30
Dimethicone 0.30
C Sodium hydroxide 1.60
D Phenoxyethanol, 0.50
Methylparaben,
Propylparaben, Butylparaben Ethylparaben E Fragrance 0.30
F Product of the invention 0.01-10%

Examples of the Invention The product of the invention is used in a water-in-oil emulsion formulation A PEG 30 Dipolyhydroxystearate 3
Capric acid triglyceride 3
Cetearyl octoate 4
Dibutyl adipate 3
Grape seed oil 1.5
Jojoba oil 1.5
Phenoxyethanol, 0.5
Methylparaben,
Propylparaben, Butylparaben Ethylparaben B Glycerin 3
Butylene glycol 3
Magnesium sulfate 0.5
EDTA 0.05
Amount of water to be 100 C Cyclomethicone 1
Dimethicone 1
D Fragrance 0.3
E Product of the invention 0.01-10%

Examples of the invention The products of the invention are used in shampoo or shower gel type formulations. A Xanthan gum 0.8
Amount of water to be 100 B Butylene glycol, 0.5
Methylparaben,
Methylparaben,
Ethyl paraben, propyl paraben,
Phenoxyethanol, 0.5
Methylparaben,
Propylparaben, Butylparaben Ethylparaben C Citric acid 0.8
D Sodium laureth sulfate 40.0
E Product of the invention 0.01-10%

Examples of the invention The products of the invention are used in lipstick-type formulations and other anhydrous products A mineral wax 17.0
Isostearyl isostearate 31.5
Propylene glycol dipelargonate 2.6
Propylene glycol isostearate 1.7
PEG 8 beeswax 3.0
Hydrogenated palm kernel oil glycerides, 3.4
Hydrogenated palm glyceride lanolin oil 3.4
Sesame oil 1.7
Cetyl lactate 1.7
Mineral oil, lanolin alcohol 3.0
B Castor oil Amount to be 100 Titanium dioxide 3.9
CI 15850: 1 0.616
CI 45410: 1 0.256
CI 19140: 1 0.048
CI 77491 2.048
C Product of the invention 0.01-5%

Examples of the invention The product of the invention is used in a formulation of an aqueous gel (around eyes, slimer, etc.) A Amount of water to 100 Carbomers 0.5
Butylene glycol 15
Phenoxyethanol, methylparaben, 0.5
Propylparaben, butylparaben,
Ethylparaben B Product of the invention 0.01-10%

Evaluation of cosmetic acceptance of the formulation containing the subject matter of the invention The compound obtained according to Example 2 was mixed with 10% in 0.5% xanthan gel and evaluated using the rabbit eye, in rats Toxicity studies were performed by taking a single oral dose test that showed no abnormal toxicity and a test of sensitization using guinea pigs.
Assessment of primary irritation of rabbit skin According to the method recommended by OECD Directive for the "Acute Irritation / Corrosion Effect on Skin" study, 0.5 ml was applied to the skin of 3 rabbits without diluting the formulation described above. Apply at a dose of

21/02/82 Official Journal of the French
The products are classified according to the criteria defined in 1/2/1982 Decision published in Republic ("JORF").

From the results of this test it was possible to conclude that the formulation containing the compound obtained according to Example 2 was classified as non-irritating to the skin.
Evaluation of Rabbit Eye Irritation OECD No. dated February 24, 1987 for the study of “Effects of Acute Irritation / Corrosion on the Eye”. In accordance with the method recommended by 405 Direct, the formulation described above was instilled once into the eyes of three rabbits at a rate of 0.1 ml.

From the results of this test, it was concluded that the formulation can be considered as non-irritating to the eye in the sense of Direct 91/326 EEC when used as is, ie without dilution.
Study on Absence of Abnormal Toxicity when Orally Administered to Rats Once OECD No. 24, Feb. 24, 1987 According to 401 Directive recommended and cosmetically compatible protocol, the formulation described above was administered orally once to 5 male rats and 5 female rats at a dose of 5 g / kg body weight.

The measured LD0 and LD50 are 5,000 mg / Kg or more. Therefore, the tested formulations are classified as not being in danger of consumption.
Assessment of skin sensitization in guinea pigs A maximization test described by Magnusson and Kligmann in the formulation described above, ie Direct Line No. OECD. Received protocol matching 406.

  The formulations described in the examples given above are classified as not sensitizing the skin on contact with the skin.

  By way of comparison, commercial wheat protein that had been cross-linked according to the method of Example 1 induced sensitization in 40% of animals that were tested according to the test protocol.

Claims (17)

  A method for producing a crosslinked polymer of at least one carbohydrate component containing at least one primary alcohol functional group, wherein the carbohydrate component has at least one primary alcohol functional group and a crosslinking agent. A method comprising obtaining a crosslinked polymer of said carbohydrate component by crosslinking at least one reactive functional group in an aqueous phase.   The method of claim 1, wherein the carbohydrate component is selected from polysaccharides, oligosaccharides, polyols or mixtures thereof.   The method of claim 1, wherein the cross-linking agent is selected from polycarboxylic acid chlorides, carboxylic anhydrides, polyisocyanates, polythioisocyanates, polyaldehydes or mixtures thereof.   The method according to claim 1, wherein the carbohydrate component is subjected to hydrolysis before reacting in the aqueous phase and before contacting with the crosslinking agent.   The method of claim 1, further comprising removing compounds insoluble in the aqueous phase after the crosslinking reaction.   A method for producing a crosslinked polymer of at least one carbohydrate component containing at least one primary alcohol functional group, wherein the carbohydrate component containing at least one primary alcohol functional group is dissolved in an aqueous phase. After that, a phase containing a crosslinking agent having at least one reactive functional group and the aqueous phase are combined to obtain a crosslinked polymer of the carbohydrate component having a molecular weight equal to or greater than 50,000 daltons. Mixing comprising sufficient time.   A crosslinked polymer obtainable by the method according to claim 1.   A crosslinked polymer obtainable by the method according to claim 6. The carbohydrate component is a) -galactomannan derived from galactomannan, guar or carob beans,
-Carrageenan, a carrageenan derived from red algae,
-Glucomannan, glucomannan derived from konjac gum,
-Polysaccharides with primary alcohol functional groups derived from fermentation, xanthan, hyaluronic acid,
-Cellulose,
A cellulose component selected from the group consisting of hydroxypropylmethylcellulose and methylethylcellulose, methylhydroxymethylcellulose;
-Polyholoside,
-Agar,
Alginate, sodium salt of alginic acid, sodium alginate,
-Starch, amylopectin, amylose, starch derived from wheat, starch derived from rice, starch derived from potato, starch derived from corn,
-Chitosan,
-Card run,
-Adragante rubber or tragacanth rubber,
-Gum arabic or gum acacia,
-Kia rubber,
-Elemi rubber,
-Gellan gum,
-Gatch rubber or Indian rubber,
-Karaya gum,
-Shellac, and-manila rubber,
A polysaccharide selected from the group consisting of:
b)-cyclodextrin, alpha cyclodextrin, beta cyclodextrin or gamma cyclodextrin and any mixtures thereof,
-Dextrin,
-Raffinose, cellobiose, sucrose, maltose, lactose, trehalose, dihydroxyacetone (DHA), fructose, sorbose, ribose, deoxyribose, xylose, arabinose, glucose, mannose, galactose, erythrose, threose, allose, atrose, gulose, idose , Talose, erythrulose, xylulose, psicose, tagatose, cedoheptulose, xylobiose, chitobiose, nigerose, aminaribiose, cojibiose, sofolose, gentianose, gentiobiose, melibiose, melezitose, turanose, stachyose, bell bass course
-Gluconic acid, gluconolactone, glucosamine, galactosamine, galactosamine sulfate, glucosamine sulfate,
-Saponins, saponins derived from quilla bark,
-Guanosine, uridine,
-Streptomycin sulfate, and-riboflavin,
Oligosaccharides selected from the group consisting of monosaccharides and disaccharides, and c) -glycerol, sorbitol, erythritol, maltitol, sorbitol, mannitol, lactitol, galactitol, ribitol, glycerol, xylitol, Myo-inositol and polyethylene glycol,
A polyol selected from the group consisting of:
The crosslinked polymer of claim 7 selected from the group consisting of:   Xanthan that the carbohydrate component is crosslinked using sebacic acid dichloride, cellulose that is crosslinked using sebacic acid dichloride, rubber derived from carob beans that is crosslinked using sebacic acid dichloride, xylitol that is crosslinked using sebacic acid dichloride, sebacine Maltose to be crosslinked with acid dichloride, carrageenan to be crosslinked with terephthalic acid dichloride, raffinose to be crosslinked with terephthalic acid dichloride, acacia rubber to be crosslinked with terephthalic acid dichloride, glycerol to be crosslinked with terephthalic acid dichloride and A mixture selected from the group consisting of a mixture of xanthan, a mixture of mannitol and inulin crosslinked with terephthalic acid dichloride, or a polysaccharide which is a mixture thereof. Crosslinked polymer in claim 7.   A composition comprising the polymer according to claim 7, wherein the composition is selected from a cosmetic composition, a dermatological composition and a pharmaceutical composition.   11. A composition comprising the polymer of claim 10, wherein the composition is selected from a cosmetic composition, a dermopharmaceutical composition, and a pharmaceutical composition.   A cosmetic care method selected from the group consisting of tightening the skin, conditioning the skin, obtaining wrinkle reduction, obtaining small wrinkle reduction and improving the biomechanical properties of the skin, claiming Item 8. A method comprising applying the crosslinked polymer according to Item 7 to the skin.   A cosmetic care method selected from the group consisting of tightening the skin, conditioning the skin, obtaining wrinkle reduction, obtaining small wrinkle reduction and improving the biomechanical properties of the skin, claiming Item 11. A method comprising applying the crosslinked polymer according to Item 10 to the skin.   The method according to claim 13 or 14, wherein the cosmetic care is performed on at least a part selected from the group consisting of a face, a neck, a hand and a neckline.   A cosmetic care method comprising topically applying a cosmetic composition comprising the polymer of claim 7.   A cosmetic care method comprising topically applying a cosmetic composition comprising the polymer of claim 10.