JP2005530600A - P / O emulsion containing amino functional polyol - Google Patents

Abstract

The polyol-in-oil emulsion comprises at least one amino functional polyol such as (R) -panthenol in an oil-immiscible polyol phase having a melting point of less than 100 ° C., an oil phase, and at least one emulsifier. .

Description

  This invention relates to polyol-in-oil emulsions containing amino-functional polyols (P / O emulsions), processes for their preparation, polyol-in-oil-in-water emulsions containing these emulsions (P / O / W emulsions), cosmetics And / or their use in pharmaceutical, cleaning, food or agricultural compositions, and such cosmetic and / or pharmaceutical, cleaning, food or agricultural compositions. The invention further relates to the use of amino functional polyols as solvents for organic compounds that are insoluble or poorly soluble in lipophilic and hydrophilic media.

  In cosmetic and / or pharmaceutical, cleansing, food or agricultural compositions, emulsions of active ingredients are often used that can be prepared in a composition suitable for the desired application. The preparation of polyol-in-oil emulsions and polyol-in-oil-in-water emulsions is known per se. With the aid of such an emulsion, cosmetic and / or pharmaceutical, cleaning, food or agricultural active ingredients can be converted into a form suitable for the application. DE-A-43 41 114 relates to an anhydrous X / O emulsion comprising a non-aqueous oil-immiscible phase and an oil phase. This non-aqueous oil-immiscible phase may contain active ingredients, which may also be in solid form, for example for pharmaceutical, cosmetic or technical use. This emulsion is prepared using a special emulsifier with a maximum HLB value of 6 or a W / O emulsion. Polyols that can be used include propylene glycol, butylene glycol, polyalkylene glycol, glycerol, polyglycerol, and mixtures thereof.

  DE-A-43 41 113 relates to a stable complex emulsion of the X / O / Y type. Here, X is an oil immiscible component, O is an oil phase, and Y is an aqueous phase.

  In particular, W / O / W emulsions and P / O / W emulsions are described, in which case the polyol phase used is again propylene glycol, butylene glycol, polyalkylene glycol, glycerol, polyglycerol, or A mixture thereof may also be used.

  Various cosmetic or pharmaceutical, cleansing, food or agricultural active ingredients are insoluble or poorly soluble or slightly less soluble in hydrophilic and lipophilic media. In particular they are poorly soluble or insoluble in water or oil. Such active ingredients are therefore often applied only in a finely dispersed form of the solid in the carrier medium, which leads to drawbacks during formulation, metering and application. The presence of solids results in complex formulations of cosmetic or pharmaceutical, cleansing, food or agricultural compositions. In addition, it is often the case that the active ingredient is not supplied in a form suitable for the application.

  One object of the present invention is to provide cosmetic or pharmaceutical, cleaning, food or agriculturally compatible solubility promoters for active ingredients that are insoluble in hydrophilic and lipophilic media. In addition, a polyol-in-oil emulsion with a new type of polyol component is provided, which can act as a solubility promoter for the active ingredient. The disadvantages of known active ingredient formulations should be overcome.

  This object is achieved according to the invention by a polyol-in-oil emulsion comprising at least one amino functional polyol in an oil-immiscible polyol phase, an oil phase and at least one emulsifier having a melting point of less than 100 ° C. The

  As amino functional polyol, any suitable amino functional polyol having a melting point of less than 100 ° C., preferably less than 50 ° C., can be used. The expression “amino functional group” polyol means that there is at least one amine or amide group in the polyol. The polyol also has at least two hydroxyl groups. It may be an aliphatic polyol, an aromatic polyol, or an aromatic / aliphatic polyol. Preferably it is an aliphatic polyol. Particularly preferably, there are 2 to 10, particularly preferably 2 to 5, in particular 2 to 3 hydroxyl groups in the polyol. In addition to the functional group, the amino functional polyol can have a carbonyl group, a carboxyl group, a thiol group, and a carbon-carbon double bond or triple bond. In addition, they may have an ether group. If at least two free hydroxyl groups are present in the molecule, some hydroxyl groups present in the molecule may be etherified. Preferably, the amino functional polyol used in accordance with this invention contains one or two amide groups.

  According to the invention, it is preferred to use amino functional polyols having two or three hydroxyl groups and one or two amide groups. They may additionally have thiol groups or carboxyl groups. Preferably, the compound contains 5 to 15 carbon atoms, particularly preferably 7 to 12 carbon atoms.

  Preferably, the amino functional polyol is a pantothene derivative of general formula (I).

Preferably, R is a group CH ₂ -OR ^1. Preferably R ¹ is hydrogen or C _1-6 -alkyl, in particular hydrogen or C _1-3 -alkyl.

  Particular preference is given to using pantothenic acid, panthenol or pantethein. The pantothene derivative is preferably of the (R) type. Pantothenic acid can also be used in the form of a salt, and the pantothenic derivative (R) -panthenol is particularly preferred.

  Preferably, the compound used according to the invention has a molecular segment derived from pantoic acid and a molecular segment derived from β-alanine if it is a compound compatible with pantothenic acid.

Panthenol and pantothenic acid are known from the pharmaceutical field for wound healing and from hair treatment compositions and animal feed additives. The preparation can take place via biosynthesis from 2-oxo-3-methylbutanoic acid or from pantolactone. Still other preparation processes are generally known. Beilstein EIV 4, 25
71, Beilstein EV 18/1, 22, and Beilstein E IV 4, 2569f, and Isler et al., Vitamin II, pp. 309-339, Thieme-Verlag, Stuttgart, Reference may also be made to 1988. There is also extensive patent literature describing the use of pantothenic derivatives, especially panthenol, in cosmetic and pharmaceutical compositions.

  One or more polyol phases may be present in the polyol-in-oil emulsion (P / O emulsion) according to the invention. Preferably there is one polyol phase comprising at least one amino functional polyol as described above. Preferably, the polyol phase comprises at least 50% by weight, particularly preferably at least 80% by weight and in particular at least 95% by weight of amino functional polyol, based on the total polyol phase. Since pantothenic derivatives may be hygroscopic compounds, water may also be present in the polyol phase in an amount of up to 20% by weight, preferably up to 10% by weight, in particular up to 5% by weight, based on the entire polyol phase. Good. Preferably, the polyol phase is largely or completely anhydrous. Here, the sum of the pantothene derivative, other polyols and water is 100% by weight.

  Further polyols that may be present are conventionally known polyols such as propylene glycol, butylene glycol, ethylene glycol, polyalkylene glycol, glycerol, polyglycerol, glycoside, sorbitol, mannitol, pentaerythritol, Trimethylolpropane, or a mixture thereof. Suitable polyalkylene glycols are in particular polyethylene glycols and polypropylene glycols. Further suitable polyols are known to those skilled in the art, for example aromatic polyols such as emodin / aloe vera.

  Particularly preferably, the amino functional polyol as described above is present as the sole polyol in the polyol phase.

  According to this invention, the polyol phase is immiscible with the oil. This means that during the preparation of the P / O emulsion according to the invention, preferably the polyol is not soluble in the oil phase and the oil is not soluble in the polyol phase. Some deviations from this (for example solubility of up to 5% by weight, preferably up to 1% by weight, in particular up to 0.5% by weight) are not meaningful here. That means that in a P / O emulsion, an emulsion of the polyol phase is present in the oil phase and no solution of the polyol is present in the oil.

  All oils that may be used in the oil phase are known suitable oils and mixtures thereof. Examples of suitable oils are silicone oils and derivatives thereof, which may be linear or cyclic natural ester oils such as grape seed oil, olive oil or sunflower oil, synthetic ester oils such as neutral oils. Well, for example, citrate ester, lactate ester, oleate ester, salicylate ester, cinnamic acid ester or other organic photoprotective filters, or camphor derivatives, triglycerides, fatty alcohols or mixtures thereof, linear or branched Paraffin oil, isoparaffin oil, and ester oil may be used.

  In the P / O emulsion, the weight ratio of the polyol relative oil phase is preferably 10:90 to 90:10, particularly preferably 25:75 to 75:25, especially 40:60 to 60:40.

The emulsifier that may be used is any desired suitable emulsifier suitable for the preparation of an emulsion of an amino functional polyol in oil. Examples of suitable emulsifiers are glycerol esters, polyglycerol esters, sorbitan esters, sorbitol esters, fatty alcohols, propylene glycol esters, alkyl glucositol esters, sugar esters, lecithins, silicone copolymers, wool oils, and mixtures or derivatives thereof. It is. Glycerol esters, polyglycerol esters, alkoxylates and fatty alcohols, and isoalcohols are, for example, caster fatty acids, 12-hydroxystearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, stearic acid, myristic acid, lauric acid, It can also be derived from capric acid. In addition to the esters, succinic acid esters, amides or ethanolamides of fatty acids may also be present. Suitable fatty acid alkoxylates are in particular ethoxylates, propoxylates or ethoxylate / propoxylate mixtures.

  The amount of emulsifier can be matched to the actual requirements. Preferably, the emulsifier is used in an amount of 0.1 to 20% by weight, particularly preferably 0.5 to 15% by weight, in particular 1 to 8% by weight, based on the total P / O emulsion. In some cases, concentrations that deviate from this may be required.

  According to one embodiment of the invention, the polyol phase may contain cosmetic and / or pharmaceutical active ingredients that dissolve within the phase. This may also be an active ingredient for cleaning, food or agriculture.

  The active ingredient is preferably an organic compound that is insoluble or poorly soluble in lipophilic and hydrophilic media. The compounds here are not particularly soluble or poorly soluble in water and oil. Any suitable active ingredient can be used provided it is soluble in the amino functional polyol or in the polyol phase containing the amino functional polyol. Suitable active ingredients are, for example, dichlorphenac, ibuprofen, acetylsalicylic acid, erythromycin, ketoprofen, cortisone, glucocorticoid.

  Also suitable are cosmetic active ingredients, which are particularly sensitive to oxidation or hydrolysis, such as polyphenols. Here, catechin (epicatechin, epicatechin-3-gallate, epigallocatechin, epigallocatechin-3 gallate, etc.), flavonoid (luteolin, apigenin, rutin, quercetin, fisetin, ken Phenol, rhamnetin, etc.), isoflavones (genistein, daidzein, glycitein, prunetine, etc.), coumarins (daphnetin, umbelliferone, etc.), emodin, resveratrol, and oregonine.

  Vitamins such as retinol, tocopherol, ascorbic acid, riboflavin and pyridoxine are preferred.

  Also suitable are complete extracts from plants, which include, inter alia, the molecules or classes of molecules mentioned above.

  Any suitable amount of active ingredient can be mixed into the polyol phase. The amount that can be mixed is often determined by solubility and by the final field of use of the preparation. In general, 0.01 to 95% by weight, preferably 0.1 to 80% by weight, in particular 2 to 50% by weight, of the active ingredient is mixed with the amino functional polyol or polyol phase, Based on total with polyol. Expressed in another way, the weight fraction of the stated polyol can be replaced by the amount of active ingredient mentioned above in the amount of polyol phase. For example, 0.01 to 95% by weight of the polyol phase, based on the pure polyol phase, can be replaced by the active ingredient. This means that the above explanation regarding the fraction of the polyol phase emulsion is still applicable. Next, the content of the polyol or amino functional polyol is reduced by exactly the same fraction as the active ingredient present in the polyol phase.

  It is also possible to add a conventional carrier system for the active ingredient using amino-functional polyols to reach the polyol phase.

  The P / O emulsions described above can also be emulsified with water or water-in-oil emulsions. This results in a polyol-in-oil emulsion (P / O / W emulsion) comprising at least one emulsion as described above and additionally at least one aqueous phase. Such complex emulsions may correspond in structure to the emulsions described in DE-A-43 41 113, in which the polyol component is changed in an embodiment according to the invention. The structure of the polyol-in-oil emulsion can correspond to that of the emulsion described in DE-A-43 41 114 in which the polyol phase according to the invention is used as the polyol phase.

  When introducing the P / O emulsion according to the invention into a water or aqueous system, the weight ratio of the individual phases can be varied within wide limits. Preferably, the weight fraction of the P / O emulsion in the finally obtained P / O / W emulsion is 0.01 to 80% by weight, particularly preferably 0.1%, based on the total P / O / W emulsion. ~ 70% by weight, in particular 1-30% by weight.

  When the P / O emulsion according to the invention is introduced into the O / W emulsion, the fraction of the P / O emulsion is preferably 0.01-60, based on the finally obtained P / O / W emulsion. % By weight, particularly preferably 0.1-40% by weight, in particular 1-30% by weight. In the O / W emulsion used for this purpose, the oil fraction is preferably 1 to 80% by weight, particularly preferably 1 to 30% by weight, based on the O / W emulsion used.

  The individual phases of the emulsion can also have customary ingredients known for the individual phases. For example, the individual phases may contain further pharmaceutical or cosmetic, cleansing, food or agricultural active ingredients that are soluble in these phases. The aqueous phase may include, for example, organic soluble photoprotective filters, hydrophilically coated micropigments, electrolytes, alcohols, and the like. Some or all of the phases may additionally contain solids, preferably selected from dyes, microspheres, silica gel, and similar materials. The oil phase includes, for example, organically modified viscosity minerals, hydrophobically coated pigments, organic oil-soluble photoprotective filters, oil-soluble cosmetic active ingredients, waxes, metal soaps such as magnesium stearate, petrolatum, Or a mixture thereof. Dyes that may be mentioned are titanium dioxide, zinc oxide, and barium sulfate. In particular, titanium dioxide or zinc oxide is customary as a photoprotective filter in cosmetics and can be applied to the skin in a particularly smooth and uniform manner by means of the emulsion according to the invention. Microspheres or silica gels can be used as carriers for active ingredients, and waxes can be used as a base for polishes, for example.

  The aqueous phase can further include glycerol, polyethylene glycol, propylene glycol, ethylene glycol, and similar compounds, and derivatives thereof.

  Thus, drugs that are administered orally but are not stable under conditions prevailing in the stomach or that should be effective elsewhere in the gastrointestinal tract are delivered to their site of action using emulsions according to this invention. It is also possible to do. This emulsion does not break in the stomach, that is, it passes unchanged into the stomach. The contained active ingredient is therefore only released in the gastrointestinal tract afterwards due to degradation or dissolution of the emulsifier. The choice of the emulsifier can be adjusted in this regard to the conditions present at the site of action.

  The use of conventional auxiliaries and additives in the emulsion is known to those skilled in the art.

  The preparation of P / O emulsions according to the invention can take place by known processes, for example as described in DE-A-43 41 114 and DE-A-43 41 113. For preparation, the polyol phase and the oil phase, each optionally containing an emulsifier, are separately heated to a temperature in the range of 20 to 90 ° C. and then combined with stirring.

  Depending on the composition, the volume ratio of the phases, and any solid fraction that may be present, the emulsion may be prepared and present in the form of a solid emulsion or a flowable emulsion. These are very stable emulsions with high long-term stability under normal handling conditions. In particular, they meet conventional stability requirements in the temperature range of −5 ° C. to + 45 ° C. The droplets present in the emulsion are very resistant, so the emulsion is particularly suitable as a carrier for many types of active ingredients.

  Emulsions prepared using the above emulsifiers can be obtained by a simple mixing operation with stirring, in which case the stability of the emulsion is generally affected by the type of stirring device and stirring tool introduced. There is little if any. Any suitable standard commercial stirrer can be used to prepare the emulsion according to the invention.

  The emulsions according to the invention are preferably used in cosmetic and / or pharmaceutical compositions and also in cleaning, food or agricultural compositions. The invention thus also relates to their cosmetic and / or pharmaceutical compositions comprising at least one of the emulsions. The cosmetic and / or pharmaceutical composition may be hand lotion or body lotion, oil, ointment, paste, gel, lip care product, face care product, and similar compositions. The composition may be used in the form of a solid, liquid or aerosol.

  The invention further relates to the use of amino functional polyols as solvents for organic compounds that are insoluble or poorly soluble in lipophilic and hydrophilic media. Suitable molecules or groups of molecules include, for example, sphingosine, ceramide, and triterpenic acids such as oleanolic acid, betulinic acid, betulin, ursonic acid, boswellia acid, 18-β-glycyrrhetinic acid. There are also forskolin, sclareolide, andrographolide.

  Likewise suitable are total extracts from plants, which include, inter alia, the molecules or classes of molecules described above.

  Suitable lipophilic media here are those mentioned above, and suitable hydrophilic media are aqueous media with a water content of at least 80% by weight, preferably at least 90% by weight, in particular at least 95% by weight. Insoluble compounds are considered to be compounds whose solubility is less than 3%, preferably less than 1%, in particular less than 0.5%.

  The invention also relates to a solution of an organic compound which is preferably insoluble or poorly soluble in lipophilic and hydrophilic media in an amino functional polyol having a structure as described above.

  In addition, the invention provides amino functionality as a solubility promoter for introducing cosmetic and / or pharmaceutical, cleansing, food or agricultural active ingredients into polyol-in-oil or polyol-in-water emulsions. Relates to the use of base polyols.

  Emulsions according to this invention can demonstrate delivery and depot effects for the active ingredients present therein. They can thus act not only as a carrier but also as a depot, thereby allowing a delayed release of the active ingredient over a period of time.

  The emulsion according to the invention has the following advantages.

  Active ingredients that are sensitive to oxidation and sensitive to hydrolysis can be encapsulated in a stable manner, in particular in a manner that is stable for long periods of storage. Erosion due to moisture on the active ingredient can be reliably prevented with the emulsion according to the invention.

  Active ingredients that are insoluble or poorly soluble in hydrophilic and lipophilic media can be administered in the form of emulsions or dispersions.

  By using the emulsion according to the invention, the penetration properties of the cosmetic or pharmaceutical composition can be positively influenced. In particular, with the composite emulsions described above, depot effects and improved penetration can be achieved.

  By forming a liquid crystal gel network structure in the composite emulsion described above, the skin permeable barrier is overcome by building an ordered state corresponding to the ordered state of the skin lipid barrier. In such a carrier system, the penetration properties of the pharmacological and cosmetic active ingredients are decisively improved.

  The invention is illustrated in more detail by the following examples.

Example Example 1
Preparation example of POW containing pantothenyl ethyl ether

  The preparation is performed according to the following sequence of processing steps.

  1. Heat Phase A and Phase B separately to 80 ° C.

  2. Add Phase A to Phase B and homogenize for 1 minute.

  3. Cool to about 35 ° C. and homogenize for 1 minute.

  4). Cool Phase AB to 25 ° C. and mix Phase C using a spatula.

  5). Add phase D to phase E at room temperature and homogenize for 1 minute.

  6). Add phase DE to phase ABC and homogenize for 0.5 min.

  The physical stability of PO and POW emulsions is 3 months at 50 ° C. and 6 months or more at room temperature. Evaluation was performed visually and by optical microscope.

Example 2
Preparation example of POW containing pantothenyl ethyl ether and substitution of PO silicone oil phase with grape seed oil

  Preparation takes place as described in Example 1.

  The physical stability of PO and POW emulsions is 3 months at 50 ° C. and 6 months or more at room temperature. Evaluation was performed visually and microscopically.

Example 3
Examples of PO emulsions containing active ingredients

  The preparation is performed as described in Example 1 for the PO emulsion.

  The physical stability of the PO emulsion is 3 months at 50 ° C. and 6 months or more at room temperature. Evaluation was made visually.

Claims (12)

  A polyol-in-oil emulsion comprising at least one amino functional polyol in an oil-immiscible polyol phase, an oil phase and at least one emulsifier having a melting point of less than 100 ° C. The amino functional group polyol has the general formula (I):

The emulsion according to claim 1, which is a pantothene derivative of   3. Emulsion according to claim 2, characterized in that the pantoten derivative is (R) -panthenol.   4. Emulsion according to any of claims 1 to 3, characterized in that at least 50% by weight of amino functional polyol is present in the polyol phase.   5. Emulsion according to any of claims 1 to 4, characterized in that the polyol phase contains cosmetic and / or pharmaceutical, cleaning, food or agricultural active ingredients dissolved in the phase.   6. The polyol phase and the oil phase, each of which can contain an emulsifier, are heated separately to a temperature in the range of 20 to 90 [deg.] C. and then combined by stirring, according to claim 1-5. Process for the preparation of emulsions.   A polyol-in-oil-in-water emulsion comprising at least one emulsion according to any of claims 1-5 and additionally at least one aqueous phase.   Use of an emulsion according to any one of claims 1 to 5 and 7 in cosmetic and / or pharmaceutical, cleaning, food or agricultural compositions.   A cosmetic and / or pharmaceutical, cleaning, food or agricultural composition comprising at least one emulsion according to any of claims 1-5 and 7.   Use of amino functional polyols as solvents for organic compounds that are insoluble or poorly soluble in lipophilic and hydrophilic media.   A solution of an organic compound that is insoluble or poorly soluble in lipophilic and hydrophilic media in an amino functional polyol.   Use of an amino functional polyol as a solubility promoter for introducing cosmetic and / or pharmaceutical, cleansing, food or agricultural active ingredients into a polyol-in-oil emulsion or a polyol-in-oil-in-water emulsion.