WO2008014505A2

WO2008014505A2 - Blends for improved solubilization of active and functional organic compounds

Info

Publication number: WO2008014505A2
Application number: PCT/US2007/074710
Authority: WO
Inventors: Steven H. Bertz; Michael D. Drzewinski; Ilya Makarovsky
Original assignee: ISP Investments LLC
Current assignee: ISP Investments LLC
Priority date: 2006-07-28
Filing date: 2007-07-30
Publication date: 2008-01-31
Anticipated expiration: 2009-01-28
Also published as: WO2008014505A3

Abstract

In accordance with this invention, there is provided a blend which comprises the reaction product of an aryl alcohol and an alkyl or aryl carboxylic acid and the reaction product of a C1-C22 linear or branched, saturated or unsaturated alcohol and a hydroxy acid. The blend provides enhanced solubilization of active and functional organic compounds.

Description

BLENDS FOR IMPROVED SOLUBILIZATION OF ACTIVE AND FUNCTIONAL ORGANIC COMPOUNDS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of U.S. Provisional Application

Serial No. 60/834,221 , filed on July 28, 2006, the disclosure of which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to blends useful for the solubilization of active and functional organic compounds.

BACKGROUND OF THE INVENTION

[0003] Many commercial products, e.g., personal care, pharmaceutical, agricultural and industrial products, contain active or functional organic materials which require solubilization in the form of a solution, emulsion or dispersion, in aqueous or non-aqueous form. For example, personal care sunscreen compositions are well known in the art. See for example, U.S. Patent No. 6,436,376 and U.S. Publication Nos. 2003/0021847 and 2006/0002872. A personal care sunscreen formulation containing aromatic compounds such as avobenzone (Escalol^®) or benzophenone as active UVA/UVB absorbing ingredients, requires a solubilization agent to keep it in an emulsion and to prevent crystallization. Several such solubilizers are known, e.g. ethyl benzoate or a C-12-C1₅ alkyl benzoate; however, the former compound is a strong irritant, and the latter is only a poor solvent for avobenzone. Thus, it is desired to provide new and improved sunscreen formulations with different active materials and improved solubilizers for such formulations and other formulations containing an active or functional organic material.

[0004] U.S. Publication No. 2006/0002872 discloses topically applicable photoprotective compositions containing at least one 1 ,3,5-triazine UV-screening agent and a mixture including an arylalkyl benzoate compound and an oil containing in its structure at least one amide unit. However, there is no suggestion of the blends of this invention.

SUMMARY OF THE INVENTION

[0005] We have discovered that a blend which comprises the reaction product of an aryl alcohol and an alkyl or aryl carboxylic acid and the reaction product of a C₁-C₂₂ linear or branched, saturated or unsaturated alcohol and a hydroxy acid provides enhanced solubilization of active and functional organic compounds.

[0006] In accordance with this invention, there is provided a blend which comprises the reaction product of an aryl alcohol and an alkyl or aryl carboxylic acid and the reaction product of a C_rC₂₂ linear or branched, saturated or unsaturated alcohol and a hydroxy acid. The blend provides enhanced solubilization of active and functional organic compounds.

[0007] In another aspect, this invention provides compositions comprising at least one active or functional organic compound and the above-described blend. In preferred embodiments, the active or functional organic compound is selected from the group consisting of a personal care active, a cosmetic active, a pharmaceutical active, an industrial active, an agricultural active and a preservative active.

DETAILED DESCRIPTION OF THE INVENTION

[0008] Blends of the esters described herein have been found to give better performance than the individual components for dissolving a broad spectrum of active or functional organic compounds, including, for example, sunscreen actives.

[0009] For the purposes of the present invention, one of the esters (a) is prepared from an aryl alcohol and an alkyl or aryl carboxylic acid by known techniques. Preferred aryl alcohols include C₆-Ci₈ alcohols. Preferred aryl groups include phenyl and substituted phenyl. The alkyl portion of the carboxylic acid can contain 1 to 22, preferably 6 to 18 carbon atoms. The aryl portion of the aryl carboxylic acid can contain 6 to 18 carbon atoms. Preferred aryl groups include phenyl and substituted phenyl. Particulary preferred examples of ester (a) are phenethyl cyclohexane-carboxylate and phenethyl benzoate (X-Tend^® 226).

[0010] Examples of reaction products that are prepared from aryi alcohols and aryl carboxylic acids include, but are not limited to, the following esters: benzyl benzoate, p-methylbenzyl benzoate, 1-phenylethyl benzoate, 2-phenyiethyl benzoate, 1-phenylpropyl benzoate, 3-phenylpropyl benzoate, 4-phenylbutyl benzoate, 2-phenoxyethyi benzoate, 2-(N-benzyi-N-methylamino) ethy! benzoate, 2-phenylethyl p-fluorobenzoate, 2-phenylethyl o-anisate, 1-phenylethyl o-toluate, 2-phenylethyl o-toluate, 1-phenylethyl p-toluate, 2-phenyiethyl p-toluate, 1 -phenylethyl phenylacetate, 2-phenylethyl phenylacetate, 2-pheny!ethyl 2-phenylbutyrate, 3-phenylpropyl hydrocinnamate, and 3-phenylpropyl phenoxyacetate.

[0011] Examples of reaction products of aryl alcohols and alkyl carboxylic acids include, but are not limited to, the following esters: benzyl butyrate, 2-phenylethyl acetate, 2-phenylethyl propionate, 1-phenylethyl propionate, 2-phenylethyl cyclopropanecarboxylate, 2-phenylethyl pentanoate, 2-phenylethyl neopentanoate,

2-phenylethyl cyclohexanecarboxylate, 2-phenylethyl octanoate, 2-phenylethyl

2-ethylhexanoate, and 2-phenoxyethyi propionate. Formate esters such as 2-phenylethyl formate and 2-phenoxyethyl formate are also specifically contemplated.

[0012] Further examples of the esters (a) prepared from an aryl alcohol and an alky! or aryi carboxylic acid are described in commonly owned US Publication No. 2007/0172437, the disclosure of which is hereby incorporated by reference in its entirety.

[0013] The second ester reaction product (b) is prepared from a C_rC₂₂, preferably a Ce-Ci₈, and most preferably a Ci₂-Ci₅ linear or branched, saturated or unsaturated alcohol and a hydroxy acid. Preferred hydroxy acids include lactic acid, malic acid and citric acid. Examples of esters in this latter class include C₁₂-₁₅ alky! lactate (Ceraphyl^® 41 ), di-2-ethylhexyl malate (Ceraphyl^® 45) and alkyl citrates. The aikyl citrate can be a monoalkyl citrate, a dialky! citrate or a trialkyi citrate, the alkyl portion of which preferably contains up to about 12 carbon atoms. These ester reaction products can be prepared by techniques well know to those skilled in the art.

[0014] In a preferred embodiment (a) is phenethyi cyclohexane carboxylate or phenethyi benzoate.

[0015] In a preferred embodiment (b) is a C₁₂-₁₅ alkyl lactate, a di-2-ethyihexyl malate, or an alkyl citrate.

[0016] A composition also is described herein which is a personal care, cosmetic, pharmaceutical, industrial, agricultural or preservative formulation which includes the above described blend and an active or functional organic compound or combination thereof.

[0017] For example, the composition can include one or more UV filter actives, a terpenoid, a skin lightener, a skin smoother, a fragrance, a pharmaceutical active, or a biocide active.

[0018] Preferably, the blend dissolves at least 20% of the active(s), more preferably at least 15% and most preferably at least 20%.

[0019] Many modern sunscreen formulations contain more than one filter agent in order to get continuous coverage across the UVA and UVB regions. This creates solubility problems, as each sunscreen has its own unique solubility profile, and one solubilizing agent (solvent) is not optimal for ail of them. Triazine sunscreens, e.g. Uvinul^® T 150 and Tinosorb^® S, are especially difficult to dissolve. Mixtures of X-Tend^® 226 (ISP) U.S. Publication No. 2005/0019280A 1 and various esters were tested for their ability to dissolve U.S. as well as European-approved sunscreens. The Table shows that the mixtures of the invention provide improved across-the-board performance compared to the individual components. TABLE - Solubilities of Sunscreens (% w/w at 25⁰C) in individual Solvents and Solvent Solvent Avobenzone Oxybenzone Uvinul T 15Q Tinosorb S

Component 1

2-phenylethy! benzoate (X-Tend 226) 24 36 34

Component 2

C_12-15 aikyl tactate (Ceraphyl 41) 11 15 24 6 di-2-ethylhexyl malate {Ceraphyl 45) 12 18 38 5

Blends

2:1 X-Tend 226 + Ceraphyl 41 21 32 18 27 1 :1 X-Tend 226 + Ceraphyl 41 19 29 21 23 1 :2 X-Tend 226 + Ceraphyl 41 16 24 22 18

2:1 X-Tend 226 + Ceraphyl 45 20 31 20 20 1 :1 X-Tend 226 + Ceraphyl 45 18 29 24 17 1 :2 X-Tend 226 + Ceraphyi 45 16 25 27 14

[0020] For example, X-Tend^® 226 dissolves 7% of Uvinul^® T 150 and 34% of

Tinosorb^® S, while Ceraphyl^® 41 dissolves 24% of Uvinul^® T 150 and 6% of Tinosorb^® S. Of particular significance, the 1 ;1 mixture of these emollient esters dissolves 21 % of Uvinul^® T 150 and 23% of Tinosorb^® S in addition to 19% of Avobenzone and 29% of Oxybenzone.

[0021] In another example with two ester components, Ceraphyl^® 45 dissolves

38% of Uvinul^® T 150 but only 5% of Tinosorb^® S. By adding two parts by weight of X- Tend^® 226 to one part of Ceraphyl^® 45, the solubilities of the sunscreens in the resulting mixture are at least 20%.

[0022] Actives such as personal care, cosmetic, pharmaceutical, industrial, agricultural and preservative compounds, including biocides such as antibacterial, fungicidal, herbicidal and algaecidal compounds, are effectively solubilized by the solvent blends of the invention particularly to keep the active in emulsion form without crystallizing or precipitating out of the emulsion, and without requiring the use of large amounts of solvent. Compositions of the present invention may also include combinations of actives or functional organic compounds, such as, for example, a UV filter active (one or more thereof) and a pharmaceutical (one or more thereof).

[0023] UV filter actives that may be employed in the present invention compositions, and solubilized in the blends herein, include Avobenzone, Benzophenone-3, p-Aminobenzoic acid, Camphor benzalkonium methosulfate, Homosalate, Phenylbenzimidazole sulfonic acid, Terephthalidene dicamphor sulfonic acid, Benzylidene camphor sulfonic acid, Octocrylene, Polyacrylamidomethyl benzyiidene camphor, Ethylhexyl methoxycinnamate, PEG-25 PABA, lsoamyl p- methoxycinnamate, Ethylhexyl triazone, Drometrizole trisiloxane, Diethylhexy! butamido triazone, 4-Methylbenzylidene camphor, 3-Benzylidene camphor, Ethylhexyl salicylate, Ethylhexyl p-dimethylaminobenzoic acid, Benzophenone-4, benzophenone-5, Methylene bis-benztriazoiyl tetramethylbutylphenol, Disodium phenyl dibenzimidazoie tetrasulfonate, Bis-ethylhexyloxyphenol methoxyphenol triazine, and Poiysilicone-15. Such compositions may include one or more of the aforementioned UV filter actives.

[0024] Other persona! care and cosmetic actives include terpenoids such as

Betulin, Oleanolic acid and Ferulic acid, skin lighteners such as Kojic acid, Arbutin and Mulberroside A, and skin smoothers such as Ceramides, Allantoin and Pyrrolidone carboxylic acid. Fragrance compounds are also included in this category.

[0025] Examples of pharmaceutical activess include one or more of Furosemide,

Lovastatain, Clarithromycin, Diclofenac, Famotidine, Carbamaxepine, Dipyridamole, Chlorthiazide, Spironolactone, Dilantin, Imiprantne, Melfloquine, Cyclosporine, Glyburide, and Nimodipine.

[0026] Biocide actives that provide functional benefits in the compositions of the invention include IPBC, Folpet, Carbendazin, Chlorothalonil, Cybutryne, Atrazine and Prodiamine.

[0027] The invention has been described in detail with particular reference to preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention.

Claims

CLAIMS What is claimed:

1. A blend which provides enhanced solubilization of active and functional organic compounds comprising (a) the reaction product of an aryl alcoho! and an alkyl or aryl carboxylic acid and (b) the reaction product of a C1-C22 linear or branched, saturated or unsaturated aicohol and a hydroxy acid.

2. The blend of claim 1 wherein said reaction product of an aryl alcohol and an alkyl or aryl carboxylic acid is the reaction product of an aryl aicohol and an aryl carboxylic acid.

3. The blend of claim 1 wherein said reaction product of an aryl aicohol and an alkyl or aryl carboxylic acid is selected from the group consisting of benzyl benzoate, p-methylbenzyl benzoate, 1-phenyiethyi benzoate, 2-phenyiethyl benzoate, 1- phenylpropyl benzoate, 3-phenylpropyi benzoate, 4-phenylbutyl benzoate, 2- phenoxyethyl benzoate, 2-(N-benzyl-N-methyiamino) ethyl benzoate, 2-phenylethyl p- fluorobenzoate,2-phenylethyl o-anisate, 1-phenylethyl o-toluate, 2-phenylethyl o-toluate, 1 -phenylethyi p-toluate, 2-phenylethyl p-toluate, 1-phenylethyl phenylacetate, 2- phenylethyl phenyiacetate, 2-phenylethyl 2-phenyibutyrate, 3-phenylpropyi hydrocinnamate, 3-phenylpropyl phenoxyacetate, benzyl butyrate, 2-phenylethyl acetate, 2-phenylethy! propionate, 1-phenylethyl propionate, 2-phenylethyl cyciopropanecarboxylate, 2-pheny!ethyl pentanoate, 2-phenylethyl neopentanoate, 2- phenylethyl cyclohexanecarboxylate, 2-phenylethyl octanoate, 2-phenylethyl 2- ethylhexanoate, 2-phenoxyethyl propionate, 2-phenylethyl formate and 2-phenoxyethyl formate.

4. The blend of claim 1 wherein (a) is phenethy! cyclohexane carboxylate or phenethyl benzoate.

5. The blend of claim 1 wherein (b) is a C₁₂-₁₅ alkyl lactate, di-2-ethylhexyl malate or an alkyl citrate.

6. The blend of claim 1 wherein (a) is phenethyl cyclohexane carboxylate or phenethy! benzoate and (b) is a C12-1₅ alkyl lactate, di-2-ethylhexy! malate or an alkyl citrate.

7. A composition comprising at least one active or functional organic compound and the blend of claims 1-6.

8. The composition of claim 7 wherein said active or functional organic compound is selected from the group consisting of a personal care active, a cosmetic active, a pharmaceutical active, an industrial active, an agricultural active and a preservative active.

9. The composition of claim 8 wherein said active or functional organic compound is a personal care active.

10. The composition of claim 9 wherein said personal care active is a sunscreen active.

11. The composition of claim 10 wherein said sunscreen active is a UV filter active.

12. The composition of claim 8 wherein said active or functional organic compound is a terpenoid, a skin lightener, a skin smoother, or a fragrance.

13. The composition of claim 8 wherein said active or functional organic compound is a pharmaceutical active,

14. The composition of claim 8 wherein said active or functional organic compound is a biocide active.

15. The composition of claim 8 wherein at least 20% of said active or functional organic compound is dissolved in said blend.