GB2414479A - Reactive cyclodextrins derivatised with proteins - Google Patents

Reactive cyclodextrins derivatised with proteins Download PDF

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GB2414479A
GB2414479A GB0411872A GB0411872A GB2414479A GB 2414479 A GB2414479 A GB 2414479A GB 0411872 A GB0411872 A GB 0411872A GB 0411872 A GB0411872 A GB 0411872A GB 2414479 A GB2414479 A GB 2414479A
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protein
cyclodextrin
hydrolysed
derivative
cyclodextrin derivative
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Alun Robert Barnes
Jill Elizabeth Parfrey
Robert Neil Comber
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Croda International PLC
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Croda International PLC
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Priority to PCT/GB2005/002123 priority patent/WO2005116085A1/en
Publication of GB2414479A publication Critical patent/GB2414479A/en
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    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
    • C08B37/0015Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/738Cyclodextrins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q13/00Formulations or additives for perfume preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00Anti-perspirants or body deodorants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/415Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0009Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
    • C08B37/0012Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08HDERIVATIVES OF NATURAL MACROMOLECULAR COMPOUNDS
    • C08H1/00Macromolecular products derived from proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/02Preparations for cleaning the hair

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  • Gastroenterology & Hepatology (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)

Abstract

A protein-cyclodextrin derivative obtained by the reaction of a reactive cyclodextrin with a protein is claimed. Preferably the protein is a hydrolysed protein, more preferably a vegetable protein from potato, wheat or soya. The reactive cyclodextrin has an organofunctional group such as a chloro-triazinyl, epoxide, acyl halide, sulphonyl halide, anhydride or aldehyde group. Uses of the protein-cyclodextrin derivative in cosmetic preparations, for hair care, skin care, fragrance retention, malodour control are claimed. The invention includes protein-cyclodextrin derivatives having the general formula (III) <EMI ID=1.1 HE=107 WI=133 LX=464 LY=1165 TI=CF> <PC>wherein: <EMI ID=1.2 HE=34 WI=47 LX=938 LY=2411 TI=CF> <PC>and R<1>-NH is the residue of a hydrolysed protein.

Description

COMPOUNDS
The present invention relates to novel protein-cyclodextrin derivatives useful in the preparation of hair care and skin care compositions. Compounds according to the present invention are particularly useful in systems for extending fragrance retention and de-odorising applications.
Hair care and skin care compositions often contain fragrance components. By their nature these components are volatile leading to them having short retention times, therefore extra fragrance is often included in a formulation to account for this.
Fragrance components are some of the most expensive components found in such formulations and so a method of prolonging fragrance retention would be valuable in prolonging the effect of the composition as well as allowing less of the fragrance material to be included in a formulation.
Hair and skin can also develop unpleasant odours by uptake from external environmental sources such as cigarette smoke and cooking smells and from internal sources such as body odours, thus imparting an unpleasant odour to hair and skin. Reducing or eliminating the sensory detection of these malodours is highly desirable.
The term "body odour" or "body malodour", as used herein, means odours that are generated as a result of the natural functioning of a human or mammalian body.
Such odours include, but are not limited to, odours produced by microorganisms of the human or mammalian skin (i.e. bacterial decomposition of skin secretions) or urine, and mixtures thereof. Such odours are mainly organic molecules, which have different structures and functional groups, such as amines, acids, alcohols, aldebydes, ketones, phenolics, and polycyclics including aromatics and, polyaromatics. These molecules may also be made up of sulphurs containing functional groups, such as thiol, mercaptan, sulphide and/or disulphide groups.
Cyclodextrins are ring shaped molecules, built up from glucose units [D-(+ )- glucopyranose units]. Cyclodextrins occur in nature and can be produced commercially by enzymatic transformation of starch. The 3 dimensional structure of cyclodextrin molecules leads to the formation of a cavity in the centre of the molecule that can trap a 'guest' molecule. The size of the cavity depends on the number of glucose units in the ring structure. The most common forms of cyclodextrin have 6, 7 and 8 glucose units and are called alpha-, beta- and gamma- cyclodextrin respectively. Cyclodextrin will form inclusion complexes with certain materials. Inclusion complexes occur when a guest molecule becomes incorporated into the cavity of the cyclodextrin. This ability to form inclusion complexes has led to a number of common applications for cyclodextrins.
One such application for cyclodextrins is application to substrates / surfaces with the intention of removing malodors. There are many publications concerning this application of which only a few examples follow. World Patent Application No WO 2003020231 describes a composition containing cyclodextrin for use as a skin deodorant. US patent specification No US6,284,231 describes a spray formulation for use as an odour absorbing composition on inanimate surfaces. World patent specification No W09,856,340 describes powdered compositions containing cyclodextrin-encapsulated perfume for use in body odour control compositions. US patent specification No US6,436,442 describes methods for manufacturing compositions comprising cyclodextrin. This patent is concerned with a method of formulating around the problems normally associated with cyclodextrins. The application is for capturing unwanted molecules, malodours, from inanimate and animate surfaces such as skin and hair. Reference is also made to helping the effects of fragrance in the formulation to endure. The cyclodextrins preferred are the more water-soluble alpha- and gamma- cyclodextrins and beta- cyclodextrins modified to enhance water Volubility.
W09,921,532 discloses "a substantially dry, disposable, personal cleansing product useful for both cleansing and conditioning the skin/hair and providing improved fragrance delivery". The composition uses cyclodextrin and modified cyclodextrin as one example of a compound that can aid fragrance delivery in this application.
A further application of cyclodextrins is to help improve solubility, stability and availability of active compounds. US patent specification No 6,080,733 describes modified cyclodextrins containing a thioureido linking group. The modified cyclodextrin is used to solubilise anti- tumour and anti-parasitic drugs in aqueous media.
US Patent Application No US 20030144222 describes the grafting of cyclodextrin onto a biocompatible amphiphilic polymer. The purpose of the invention is to modify the cyclodextrin properties to improve water solubility of the complexed cyclodextrin, thus encouraging tissue penetration of active agents complexed with the cyclodextrin in both cosmetic and dermopharmaceutical applications.
US Patent Application No US5,324,750 describes the modification of cyclodextrins to improve solubility and stability of inclusion complexes by covalently linking active compounds to cyclodextrin for use in orally delivered compositions. The covalently linked active compounds will then be released after the cyclodextrin molecule has been metabolized to glucose.
US patent specification no. US 4 678 598 specifies the use of a methylated cyclodextrin in a shampoo formulation. The purpose of the cyclodextrin is to mitigate the strong odour of the skin sensation inducing aromatic chemical that is being applied by use of the shampoo.
None of the above prior art considers the substantivity, if any, that cyclodextrins, or compounds containing cyclodextrin, may have for the skin or the hair.
Hydrolysed proteins are common personal care ingredients that are used as conditioning and moisturising agents for skin and hair. Hydrolysed proteins are known to have substantivity to hair from aqueous systems as described in the article The use of radiolabelling techniques to measure substantivity to, and penetration into, hair of protein hydrolysates' by R.T Jones and S.P. Chahal, International Journal of Cosmetic Science, 1997, Voi 19, pages 215-226.
The present invention retains the moisturising and conditioning properties of the hydrolysed protein component and the fragrance controlled release and malodour control properties of the cyclodextrin component. The hydrolysed protein component imparts substantivity to the protein cyclodextrin component, an unexpected advantage over the un- modified cyclodextrin component.
Accordingly, the present invention provides protein-cyclodextrin derivatives obtained by the reaction of a reactive cyclodextrin and a protein, and their use in a variety of cosmetic compositions.
Preferred protein-cyclodextrin derivatives have the general formula (I): [R -(NH)z]w - (Tb-C)p (I) wherein R'-(NH) is the residue of a protein R'NH2; T is the residue of an organofunctional group attached to cyclodextrin; C is cyclodextrin; b corresponds to the number of organofunctional groups on the reactive cyclodextrin and is preferably in the range 1 to 8; p corresponds to the number of organofunctional cyclodextrin reacted with amino groups on hydrolysed protein residues and will be preferably in the range of 1 to (w x z); z is the number of primary amine groups on the hydrolysed protein R'-NH2 available for reaction with the organofunctional cyclodextrin; w is the number of hydrolysed protein residues and is preferably in the range of 1 to (p x b) .
Preferably R4-(NH) is the residue of a hydrolysed protein and more preferably a vegetable protein hydrosylate such as a hydrosylate derived from potato, wheat or soya protein, and preferably potato protein.
In a preferred embodiment a protein and a reactive cyclodextrin are reacted in the range of 50% to 200% reactive cyclodextrin by weight of active protein.
A further preferred embodiment provides a protein-cyclodextrin derivative having the general formula (111):
OR
o/l OR ROW O:/ (111)
I OR OR O
A\ WAR As
RO
wherein: o or N New NHR' and R'-NH is the residue of a hydrolysed protein.
In further aspects the invention also provides, separately, for the use of protein- cyclodextrin derivatives as fragrance delivery agents, fragrance retention agents and malodour control agents. l
The present invention therefore provides a protein-cyclodextrin derivative obtainable by reacting a protein and a reactive cyclodextrin compound in the range from 10% to 500% reactive cyclodextrin by weight of active protein, more preferably 50 to 200% reactive cyclodextrin by weight of active protein. The reactive groups on the protein component are predominantly primary amino groups. The primary amino groups are either located at the end of the polypeptide chains of the protein or as side chain groups on basic amino acids such as Iysine. The degree of hydrolysis of the protein component will affect the number of end chain primary amino groups available for reaction. The greater the degree of hydrolysis of the protein component, the higher the number of end chain primary amino groups available for reaction. Therefore the degree of hydrolysis of the protein component will determine the number of reactive sites on the protein component available for derivatisation with the reactive cyclodextrin. Thus the ratio of protein to cyclodextrin in the finished product will vary. Similarly the reactive cyclodextrin compound can have more than one group available for reaction with the protein component of the product. This can also affect the ratio of protein to cyclodextrin in the final product. Due to the possibility of multiple reaction sites on both the protein and cyclodextrin components of the present invention, the present invention could comprise: (i) one protein molecule reacted with one cyclodextrin molecule, (ii) more than one protein molecule reacted with one cyclodextrin molecule, (iii) one protein molecule reacted with more than one cyclodextrin molecule, (iv) more than one protein molecule reacted with more than one cyclodextrin molecule, i.e. a co-polymeric or cross-linked product, (v) a combination of examples (i) to (iv).
The present invention also provides the use of a protein-cyciodextrin derivative composition to prolong the fragrance perceptibility of a formulation or aqueous solution applied to skin or hair.
The terms "fragrance" and "perfume" are intended to have the same meaning in this disclosure. The fragrance or perfume is included at a level that is non-irritating to the ordinary user's skin and/or respiratory tract, yet is discernible by the human sense of smell either before and/or after application to the skin. The perfume compositions should be safe for use on skin. The perfume compositions useful herein are comprised of perfume ingredients.
Perfume loading in the cyclodextrin complexes is typically from about 0. 1% to about 20% in cyclodextrin/perfume complexes. The cyclodextrin.perfume ingredient inclusion complexes and methods of formulation useful herein, are disclosed in detail in U.S. Patent No. 5,429,628, Trinh et al. issued July 4, 1995, which is incorporated herein by reference in its entirety.
A wide variety of perfume ingredients can be used in the present invention and such perfume ingredients will be selected by the person skilled in the art. A non-limiting list of preferred volatile perfume ingredients can be found in WO 98/56340 (Petersson et al) the entire text of which is incorporated herein by reference and which is intended to be an integral part of this disclosure.
It will be appreciated that the cyclodextrin derivative can be used to complex "actives" other than a perfume or fragrance. Thus these derivatives can be used to deliver to the skin or hair active agents such as antifungal agents, anti-dandruff agents, antibacterials, antibiotics, UK protective agents or the like. It is therefore possible, for the first time, to create a long lasting anti-dandruff shampoo or conditioner as a result of the slow release of active agent directly onto the hair.
Furthermore, as the active ingredient is released the emptied cyclodextrin moieties become available to absorb any malodour which might occur in the course of the users normal activities.
It is possible that a combination of compounds could be complexed with cyclodextrin. For example a mixture of perfume ingredients and an antifungal agent could be used.
The present invention provides the use of a protein-cyclodextrin derivative composition to control malodour when applied from a formulation or aqueous solution to skin or hair.
In order to form the protein cyclodextrin derivative of the present invention the protein and reactive cyclodextrin are reacted in the range from 10% to 500% reactive cyclodextrin by weight of active protein, preferably 50% to 200% reactive cyclodextrin by weight of active protein. The resulting derivative comprises 33% to 66% cyclodextrin and modified reactive amino groups of the protein in the range 10 - 100%.
We have found that hair treated with protein cyclodextrin derivatives of the present invention retains perceptible fragrance applied from a formulation for a significantly longer period than formulations without a protein cyclodextrin component.
We have found that hair treated with protein cyclodextrin derivatives of the present invention when exposed to environmental malodours exhibit a reduction in perceptible malodour.
Preferred derivatives for use according to the invention are those wherein the protein cyclodextrin derivative is the reaction product of a protein hydrolysate and a reactive cyclodextrin. More preferably the reactive cyclodextrin contains a chloro- triazine group capable of reacting with one or more amino groups of the protein, such as monochlorotriazinyl--cyclodextrin.
The protein may be derived from either animal or vegetable sources or by fermentation. It may be in the form of a chemically modified protein (for example, quaternised) provided that at least one free amino groups is still present in the protein molecule. Examples of proteins which are currently used in cosmetic formulations and can be used as the protein component of the current invention include collagen, elastin, keratin, casein, wheat protein, soya protein and silk. In this specification the term "protein" is used to include both native and hydrolysed proteins and it thus comprises both proteins properly so-called polypeptides, peptides and peptones, since the latter can all be categorised as hydrolysed proteins.
The average molecular weight of the protein component may be from 150 Daltons (D) to 500 kD, is preferably within the range from 200D to 50kD and is more preferably in the range of from 200D to 25.5kD, even more preferably 350D to 3000D expressed as weight average molecular weight (Mw) derived from size exclusion chromatography.
Especially preferred is when the protein hydrolysate is a vegetable protein hydrolysate, particularly wherein the vegetable protein hydrolysate is of potato or wheat origin.
It is necessary for the protein component to be capable of solution in water or other suitable solvent or co-solvent (such as alcohol, eg propylene glycol or polyethylene glycol) to enable reaction to occur.
The generic term "cyclodextrin" in the present invention is intended to include unsubstituted and substituted cyclodextrins both known and yet to be discovered.
Cyclodextrins suitable for use in the present invention include any of the known cyclodextrins such as unsubstituted cyclodextrins containing from 6 to 12 glucose units. Specific nonlimiting examples of such cyclodextrins include alpha cyclodextrin, beta-cyclodextrin, gamma- cyclodextrin, delta-cyclodextrin, epsilon cyclodextrin, zeta-cyclodextrin, nu-cyclodextrin, and mixtures thereof, and/or their derivatives, and/or mixtures thereof.
Suitable cyclodextrin derivatives include those cyclodextrin compounds of different degrees of substitution, specific examples of which include methyl-alpha cyclodextrin, methyl-beta-cyclodextrin, hydroxyethyl-betacyclodextrin, hydroxypropyl-alpha-cyclodextrin, hydroxypropyl-betacyclodextrin, cyclodextrin glycerol ethers, maltose-bonded cyclodextrins, cationic cyclodextrins, Quarternary ammonium cyclodextrins, anionic cyclodextrins such as carboxymethyl cyclodextrins, cyclodextrin sulfobutylethers, cyclodextrin sulphates, cyclodextrin succinylates, amphoteric cyclodextrins such as carboxymethyl/quaternary ammonium cyclodextrins, mono-3-6-anhydrocyclodextrins, and combinations thereof. Other examples of suitable cyclodextrin derivatives are disclosed in "Optimal Performances with Minimal Chemical Modification of Cyclodextrins", F Diedaini-Pilard and B. Perly, The 7th International Cyclodextrin Symposium Abstracts, April 1994, p.49; U.S. Patent No. 3,426, 011, issued to Parmerter et al. on Feb.4, 1969; U.S. Patent Nos. 3,453, 257, 3,453,258, 3,453,259 and 3,453,260, all issued to Parmerter et al. on Aug.5, 1969; U.S. Patent No. 3,553,191, issued to Parmerter et al. on Jan.5, 1971; U.S. Patent No. 3,565,887, issued to Parmerter et al. on Feb 23, 1971; U.S. Patent No. 4,535,152, issued to Szejtli et al. on Aug.13, 1865; U.S. Patent No. 4,616,008, issued to Hirai et al. on Oct.7, 1986; U. S. Patent No. 4,638,058, issued to Brandt et al. on Jan.20, 1987; U.S. Patent No. 4,746,734, issued to Tzuchiyama et al. on May 24, 1988; and U. S. Patent No. 4,678,598, issued to Ogino et al. on Jury, 1987; all of which disclosures are incorporated by reference herein. This list is not intended to be limiting. Rather it illustrates the very large range of cyclodextrins both known and yet to be discovered which can be used in the present invention.
It is also possible to use a mixture of cyclodextrins. Such mixtures absorb body odours more broadly by complexing with a wider range of odoriferous molecules having a wider range of molecular sizes.
The term "uncomplexed cyclodextrin" as used herein means that the cavities within the cyclodextrin in the composition are essentially unfilled.
The organofunctional cyclodextrin component is preferably soluble in a solvent common to the protein for efficient reaction to occur. The conditions for reaction of the organofunctional cyclodextrin with the protein to achieve efficient substitution ot primary amine groups on the protein must be carefully controlled, but will be apparent or readily determinable by those skilled in the art of protein modification.
As explained above, the organofunctional cyclodextrin component may be any of the known cyclodextrins containing from six to twelve glucose units, especially alpha- cyclodextrin, beta-cyclodextrin or gamma-cyclodextrin cyclodextrin, more especially beta-cyclodextrin. The alpha cyclodextrin consists of six glucose units, beta cyclodextrin consists of seven glucose units, gamma cyclodextrin consists of eight glucose units.
The organofunctional cyclodextrin component used for reaction with the protein component must contain at least one functional group capable of reacting with the chain terminal and/or side chain amino groups of the protein. The cyclodextrin component can contain more than one functional group capable of reacting with the chain terminal and/or side chain amino groups of the protein. Suitable reactive groups include, for example, chloro-triazinyl, epoxide, acyl halide, sulphonyl halide, anKydride, and aldehyde groups. One particular example of a reactive cyclodextrin is Cavasol W7 MCT produced by Wacker Chemie. This product comprises beta cyclodextrin containing chloro-triazinyl reactive groups.
A suitable method for the manufacture of protein / cyclodextrin compositions for use according to the invention is represented by the following steps: In a suitable vessel, the protein component is heated and the pH adjusted to ensure the conditions favour the reaction of the cyclodextrin functional group with amine groups on the protein over reaction with water in a hydrolysis reaction. A calculated quantity of organofunctional cyclodextrin is then added - the amount of cyclodextrin is calculated to modify 10-100%, preferably 50-90% of the available amino groups.
An excess of a primary amine containing compound, such as an amino acid, can then be added to ensure that all of the reactive groups on the organofunctional cyclodextrin have reacted. Following reaction, the pH is adjusted to acidic and worked up in a conventional manner. Conventional additives, such as preservatives, may then be added.
A preferred method for the manufacture of protein / cyclodextrin compositions for use according to the invention is represented by the following steps: (1) Load the protein component, preferably hydrolysed vegetable protein, into a suitable tank and heat to 20 - 90 C (preferably 60 - 80 C).
(2) Adjust pH to 6.0 - 10.0 (preferably 7.0-9.0) with sodium hydroxide.
(3) Add calculated quantity of reactive cyclodextrin (this is based on Formol titre) and is calculated to modify 10 -100% (preferably 80 - 90%) of the available amino groups, over a 30 to 120 minute period (preferably 45 to 75 minute period).
(4) Maintain temperature at 20-90 C (preferably 60-80 C) and pH at 6.0 10.0 (preferably 7.0 - 9.0) during reactive cyclodextrin addition.
(5) Maintain reaction conditions for a further 4 to 20 hours (preferably 7 - 10 hours).
(6) Add 0.5% - 4% (preferably 1%-3%) of an amino acid (optional) such as glycine and maintain temperature at 20-90 C (preferably 60-80 C) and pH at 6.0 - 10.0 (preferably 7.0 - 9.0) for 2 to 10 hours (preferably 4 to 8 hours).
(7) Acidify to pH 4.0 - 6.5 with a mineral acid such as hydrochloric acid.
(8) Preserve by addition of a preservative.
(9) Cool and adjust pH to 4.0 - 6.5.
(10) Filter through a depth filter pad to sparkling.
Accordingly a first aspect of the present invention comprises a compound of general formula (I): [R -(NH)z]w - (Tb-C)p (I) wherein R'-(NH) is the residue of a hydrolysed protein R-NH2; T is the residue of an organofunctional group attached to cyclodextrin; C is cyclodextrin; b corresponds to the number of organofunctional groups on the reactive cyclodextrin and will be preferably in the range 1 to 8; p corresponds to the number of organofunctional cyclodextrin reacted with amino groups on hydrolysed protein residues and will be preferably in the range of 1 to (w x z); z is the number of primary amine groups on the hydrolysed protein R'-NH2 available for reaction with the organofunctinal cyclodextrin; w is the number of hydrolysed protein residues and will preferably be in the range of 1 to (p x b).
R' is preferably the residue of a hydrolysed vegetable protein, such as hydrolysed wheat or potato protein, especially potato protein.
The nature of the group T. which is the residue of the organofunctional group of the reactive cyclodextrin used for reaction with the protein component to form the derivative, depends on the functional group originally present in the organofunctional cyclodextrin. For example, when the functional group originally present in the organofunctionai cyclodextrin was an acyl halide, the group T will typically contain a carbonyl group bonded directly to the nitrogen atom of the protein residue.
Preferably the group T is derived from reaction of the organofunctional cyclodextrin containing chloro-triazine groups as the functional group. In this case, in the final derivative of compound (I), the group T will contain a moiety of formula (II), with the nitrogen atom of the protein residue, R' bonded directly to one of the cyclic carbon atoms. The group C in formula (II) represents cyclodextrin. The group Y in formula (II) represents the residue of the compound used to remove the chloride group from this site that was present in cyanuric chloride from which this linking group is generally derived. In this case Y can be, but is not limited to OH, NH2, NHP, NPP', where P and P' are substituents on secondary and tertiary amines. Preferably this group, Y. is OH or an OH group deprotonated to O. y No (11) cow/ N Now R' The protein-cyclodextrin derivative preferably comprises a compound of formula (111) where R' is the residue of a hydrolysed protein; the groups R indicate that there may be more than one protein residue attached to each cyclodextrin molecule:
OR
OR O / _$0 Raft or N RO \ :$O O
RO
In the protein cyclodextrin derivative for use in the invention, carboxyl groups of the protein component and/or amino groups of the protein which are not bonded to the cyclodextrin component, can be chemically modified by reaction with a non- cyclodextrin, eg by esterification, acylation or quaternisation.
The derivatives of the present invention may be used to prepare simple aqueous compositions for application to the hair or skin, such as an aqueous "leave on" composition or an aqueous "rinse off" composition.
For such compositions, a dilute solution of the derivative in water may be used. The concentration of active ingredient in such a solution may range from 0.01% w/w to 10% w/w and is preferably 0.05% w/w to 5% w/w, more preferably 0.5% w/w to 2% w/w and most preferably about 1 % w/w.
Compounds and compositions according to the present invention can be also used in a wide variety of skin care formulations since hydrolysed proteins have substantivity for skin as well as hair. Skin care compositions include, but are in no way limited to, cleansing preparations, skin toners, moisturizers, scrubs, masks including face masks, washes, wipes, soap bars, creams, astringents, anti-ageing creams, anti-wrinkle creams, solar creams and tanning products, lip balms, make- up removers, exfoliants, perfumes, shower gels, bath oils, lotions and the like.
The present invention will now be illustrated with reference to the following
examples.
Example 1: Preparation of hydrolysed protein cyclodextrin derivative The following steps were carried out: 1. Hydrosolanum (1000g), a potato protein hydrolysate available from Croda Chemicals Europe Ltd. was loaded into a suitable beaker and stirred. The solution was heated to 75 C.
2. The pH was adjusted to 7.5 using 25% sodium hydroxide (68.8g) 3. Cavasol W7 MCT (313.5g), a compound of formula (A) below, (available from Wacker-Chemie GmbH, Hanns-Seidel-Platz 4, DE-81 737 Munchen, Germany) was added over 60 minutes.
4. During addition, pH was maintained in the range 7.0-7.5 using 25% sodium hydroxide (71.5g) and the temperature kept constant at 75 C.
5. The reaction mixture was stirred for a further 8 hours at 75 C.
6. 28% Hydrochloric acid (53.6g) was added to lower the pH to 5.5.
7. Phenoxyethanol (14.4g), potassium sorbate (3.6g) and disodium EDTA (1.8g) were added and the solution stirred overnight at room temperature.
8. The liquor was then fltered through a depth filter pad to sparkling.
OR
OR 0 / / 5-O OR o O (OR (A) R(oOR R=H i/ IN Now \ RO OR: Hi,
RO
Example 2: Preparation of quaternised hydrolysed protein cyclodextrin derivative The following steps were carried out: 1. Hydrosolanum (500g) (Croda Chemicals Europe Ltd), was loaded into a suitable beaker and stirred. The solution was heated to 75 C.
2. The pH was adjusted to 7.5 using 25% sodium hydroxide (35.1 g) 3. Cavasol W7 MCT (78.3g), (available from Wacker-Chemie GmbH, Hanns Seidel-Platz 4, DE-81737 Munchen, Germany) was added over 60 minutes.
4. During addition, pH was maintained in the range 7.0-7.5 using 25% sodium hydroxide (18.0g) and the temperature kept constant at 75 C.
5. The reaction mixture was stirred for a further 6 hours at 75 C.
6. The reaction mixture was cooled to 60 C and held at this temperature.
7. The pH of the reaction mixture was raised to 10.0 to 10.2 using 25% sodium hydroxide (22.5g).
8. 3-chloro-2-hydroxypropyltrimethyl ammonium chloride (Quab 151, available from Degussa) (31.8g) was added dropwise via a separating funnel over a one hour period with the pH of the reaction mixture maintained at 10.0 to 10.2 using 25% sodium hydroxide. 9. The reaction mixture was stirred at 60 C, with the pH maintained at 10.
0 to 10.2 using 25% sodium hydroxide (2.9g), for 4 hours.
10. 28% Hydrochloric acid (42.6g) was added to lower the pH to 4.5.
11. Phenoxyethanol (6.4g), potassium sorbate (1.6g) and disodium EDTA (0. 8g) were added and the solution stirred overnight at room temperature.
12. The liquor was then filtered through a depth filler pad to sparkling.
Example 3: Measurement of fragrance retention of a protein cyclodextrin derivative according to Example 1 applied to hair from an aqueous solution Aqueous test solutions containing the fragrance citral (a mixture of cisand trans- 3,7-dimethyl-2,6-octadienal), have been applied to hair swatches. An aqueous citral solution containing hydrolysed protein cyclodextrin derivative has been applied to hair from a rinse off system. The fragrance retention performance of the aqueous ctral solution containing hydrolysed protein cyclodextrin derivative (as in example 1) has been assessed against an aqueous citral solution containing no fragrance retention aids.
Materials used in example 3 Virgin European hair (de Meo) 10% Sodium laureth sulphate (SLES) Aqueous formulation without active Aqueous formulation with hydrolyzed protein cyclodextrin derivative (as in example 1) (1.0% active) Aqueous test formulation % byWt Water up to 100 Crillet 1 (Croda Chemicals Europe Ltd) 4.0 Citral (Sigma-Aldrich Chemical Company) 0.4 Hydrolysed protein cyclodextrin derivative qs (to provide 1.0% of active) Studv procedure 1. Virgin brown European hair was cut into swatches (300mg) and tied with cotton. The swatches were labelled A and B. 2. Each swatch was soaked in the aqueous test solution for 1 minute.
3. The A swatch was soaked in the aqueous test solution without active for 1 minute.
4. The B swatch was soaked in the aqueous test solution containing hydrolysed protein cyclodextrin derivative (1.0% active) for 1 minute.
5. The hair swatches were removed from the aqueous test solutions and rinsed under a running cold tap for 10 seconds.
6. The hair swatches were blotted dry on tissues.
7. The swatches were allowed to dry at ambient temperature and relative humidity for the desired time period (1, 2, or 6 hours) 8. The swatches were transferred to separate 5ml test tubes and methanol (HPLC grade, 5ml) added.
9. The test tubes were covered and the hair left for 30 minutes.
10. The hair swatches were removed and the methanol extracts analysed by Gas Chromatography under the following conditions: Gas Chromatooraphy analysis conditions Instrumentation: Agilent 6850 Series GO, with Agilent 7683 series injector Software: Agilent Chemstation software Injector: Injection volume: 5,ul Splitless injection Temperature: 220 C Pressure: 44.2kPa Total Flow: 138ml/min Purge flow to split vent: 130ml/min at Gamin Gas: Hydrogen Column: Agilent HP1 Methyl Siloxane Constant pressure mode H2 pressure: 44.3 kPa H2 flow: 2.8 ml/min Column average velocity: 50cm/s Oven: Initial temperature: 50 C Initial hold time: 1 min Ramp 1: 50-110 C, 20 C/min Ramp 2: 110-140 C, 5 C/min Ramp 3: 140-300 C, 40 C/min Final hold time: 7 minutes Total run time: 21 minutes Flame ionisation detector Citral shows two peaks on GO analysis (due to cis and bans isomers). The amount of citral present in the methanol extracts was determined from the ratio of the peak area detected for each peak to the peak area obtained for a sample of citral in methanol of known concentration. Fragrance retention values were calculated for each peak at each drying time using the following equation: Percentage fragrance retention = AD x 100 Where: An = Average peak area after 1 hour of drying At = Average peak area after 1, 2, 6 hours of drying The fragrance retention values for the two peaks obtained at each drying time were averaged. The results are shown in table 1, with standard deviation (SD) values for each data point, and in figure 1.
Table 1: % fragrance retention results for hair swatches treated with hvdrolysed protein cvclodextrin derivative and control Drying time / hours (SD) (SD) (SD) % fragrance retention for aqueous test solution containing 100 77.6 48 4 hydrolysed protein cyclodextrin (0) (8.7) (2.2) % fragrance retention for aqueous test solution without 100 69.0 43.9 active (0) (3 9) (1.4) # ., The study demonstrates that the hair samples treated with aqueous fragrance 1 solutions containing hydrolysed protein cyclodextrin derivative retained the A, fragrance, citral, to a greater extent than hair treated with the aqueous fragrance 2, 15 solution alone.
: Example 4: Measurement of fragrance retention of a quaternised protein :' . cyclodextrin derivative according to Example 2 applied to hair from an aqueous solution Aqueous test solutions containing the fragrance, citral (a mixture of cis- and trans- 3,7-dimethyl-2,6-octadienal), have been applied to hair swatches. An aqueous citral solutions containing quaternised hydrolysed protein cyclodextrin derivative has been applied to hair from a rinse off system. The fragrance retention performance of the aqueous citral solution containing quaternised hydrolysed protein cyclodextrin derivative (as in example 2) has been assessed against an aqueous citral solution containing no fragrance retention aids.
Materials used in example 4 Virgin European hair (de Meo) 10% Sodium laureth sulphate (SLES) Aqueous formulation without active Aqueous formulation with quaternised hydrolysed protein cyclodextrin derivative (as in example 2) (1.0% active) Aqueous test formulation % by Wt Water up to 100 Crillet 1 (Croda Chemicals Europe Ltd) 4.0 Citral (Sigma-Aldrich Chemical Company) 0.4 Quaternised Hydrolysed protein qs (to provide 1.0% of active) cyclodextrin derivative Studv procedure 1. Virgin brown European hair was cut into swatches (300mg) and tied with cotton. The swatches were labelled A and B. 2. Each swatch was soaked in the aqueous test solution for 1 minute.
3. The A swatch was soaked in the aqueous test solution without active for 1 I t minute. 8
4. The B swatch was soaked in the aqueous test solution containing quaternised hydrolysed protein cyclodextrin derivative (1.0% active) for 1 minute. :e
5. The hair swatches were removed from the aqueous test solutions and rinsed Ale, under a running cold tap for 10 seconds.
6. The hair swatches were blotted dry on tissues.
7. The swatches were allowed to dry at ambient temperature and relative humidity for the desired time period (1, 2, or 6 hours) 8. The swatches were transferred to separate 5ml test tubes and methanol (HPLC grade, 5ml) added.
9. The test tubes were covered and the hair left for 30 minutes.
10. The hair swatches were removed and the methanol extracts analysed by Gas Chromatography under the following conditions: Gas Chromatography analysis conditions
As in example 3.
Citral shows two peaks on GO analysis (due to cis and bans isomers being present).
The amount of citral present in the methanol extracts was determined from the ratio of the peak area detected for each peak to the peak area obtained for a sample of citral in methanol of known concentration. Fragrance retention values were calculated for each peak at each drying time using the following equation: Percentage fragrance retention = An x 100 Where: An = Average peak area after 1 hour of drying Al = Average peak area after 1, 2, 6 hours of drying The fragrance retention values for the two peaks obtained at each drying time were averaged. The results are shown in table 2, with standard deviation (SD) values for each data point, and in figure 2.
Table 2: % fragrance retention results for hair swatches quaternised hvdrolvsed . protein cvclodextrin derivative and control :'. | | Drying time / hours l (SD) L5D) _ eees % fragrance retention for aqueous test solution containing 100 90.0 71.8 quaternised hydrolysed protein cyclodextrin (0) (1.4) (0.1) % fragrance retention for aqueous test solution without 100 69.0 43.9 active (0) (3.9) ( 14) The study demonstrates that the hair samples treated with aqueous fragrance solutions containing quaternised hydrolyses cyclodextrin derivative retained the fragrance, citral, to a greater extent than hair treated with the aqueous fragrance solution alone.
Example 5: Measurement of fragrance delivery of a quaternised protein cyclodextrin derivative according to Example 2 applied to hair from a shampoo system Shampoo test solutions containing the fragrance, citral (a mixture of cis- and trans- 3,7-dimethyl-2,6-octadienal), have been applied to hair swatches. A shampoo containing citral and quaternised hydrolysed protein cyclodextrin derivative has been applied to hair from a rinse off system. The fragrance delivery performance of the shampoo containing quaternised hydrolysed protein cyclodextrin derivative (as in example 2) has been assessed against a shampoo formulation containing no quaternised hydrolysed protein cyclodextrin derivative.
Materials used in example 5 Virgin European hair (de Meo) Shampoo formulation without quaternised hydrolysed protein cyclodextrin derivative Shampoo formulation with quaternised hydrolysed protein cyclodextrin derivative (as in example 2) (1.0% active) Shampoo formulation % by Wt Water upto 100 Empicol ESB3 (Allbright & Wilson) 35.0 Incronam 30 (Croda Chemicals Europe Ltd) 15.0 : Crovol A70 (Croda Chemicals Europe Ltd) 3.0 Lactic acid (Sigma-Aldrich Chemical Company) to pH 6.5 - 7.0 . Citral (Sigma-Aldrich Chemical Company) 0.4 Phenova (Crodarom) 0.4 Hydrolysed quaternised protein qs (to provide 1.0% of active) cyclodextrin derivative Studv procedure 1. Virgin brown European hair was cut into swatches (300mg) and tied with cotton. The swatches were labelled A and B. 2. Each swatch was wet in running cold water for 10 seconds.
3. 5ml of shampoo formulation without hydrolysed quaternised protein cyclodextrin was massaged into the A swatch for 1 minute.
4. 5ml of shampoo formulation without hydrolysed quaternised protein cyclodextrin was massaged into the B swatch for 1 minute.
5. The hair swatches were rinsed under a running cold tap for 10 seconds.
6. The hair swatches were blotted dry on tissues.
7. The swatches were allowed to dry at ambient temperature and relative humidity for one hour.
8. The swatches were transferred to separate 5ml test tubes and methanol (HPLC grade, 5ml) added.
9. The test tubes were covered and the hair left for 30 minutes.
10. The hair swatches were removed and the methanol extracts analysed by Gas Chromatography under the following conditions: Gas Chromatouraphv analysis conditions
As in example 3.
Citral shows two peaks on GO analysis (due to cis and bans isomers). The amount of citral present in the methanol extracts was determined from the ratio of the peak area detected for each peak to the peak area obtained for a sample of citral in methanol of known concentration. Fragrance delivery values were calculated for each peak using the following equation: Percentage fragrance delivery = Weight of citral in the methanol extract x 100 Weight of citral in 5ml shampoo :' The fragrance delivery values for the two peaks obtained were averaged. The results are shown in table 3, with standard deviation (SD) values for each data point, and in figure 3.
Table 3: % fragrance delivery results for hair swatches treated with a shampoo containing quaternised hydrolysed protein cyclodextrin derivative and control % fragrance delivery for a shampoo containing 0.93 quaternised hydrolysed protein cyclodextrin (0.29) % fragrance delivery for a shampoo without quaternised 0.59 hydrolysed protein cyclodextrin _ (0.19) The study demonstrates that the shampoo containing quaternised hydrolysed protein cyclodextrin derivative delivered the fragrance, citral, to hair to a greater extent than shampoo without quaternised hydrolysed protein cyclodextrin derivative.
Example 6: Measurement of fragrance delivery of a quaternised protein cyclodextrin derivative according to Example 2 applied to hair from a conditioner system Conditioner test solutions containing the fragrance citral (a mixture of cis- and trans- 3,7-dimethyl-2,6-octadienal), have been applied to hair swatches. A conditioner containing citral and quaternised hydrolysed protein cyclodextrin derivative has been applied to hair from a rinse off system. The fragrance delivery performance of the conditioner containing quaternised hydrolysed protein cyclodextrin derivative (as in ' example 2) has been assessed against a conditioner formulation containing no quaternised hydrolysed protein cyclodextrin derivative.
Materials used in example 6 Virgin European hair (de Meo) Conditioner formulation without quaternised hydrolysed protein cyclodextrin derivative Conditioner formulation with quaternised hydrolysed protein cyclodextrin derivative (as in example 2) (1.0% active) Conditioner formulation % by Wt Water up to 100 Incroquat CTC-30 (Croda Chemicals Europe Ltd) 10.0 Crodacol CS90 (Croda Chemicals Europe Ltd) 5.0 Crillet 1 (Croda Chemicals Europe Ltd) 3. 2 Citral (Sigma-Aldrich Chemical Company) 0.4 Phenova (Crodarom) 0.4 Hydrolysed quaternised protein qs (to provide 1.0% of active) cyclodextrin derivative Study procedure 1. Virgin brown European hair was cut into swatches (300mg) and tied with cotton. The swatches were labelled A and B. 2. Each swatch was wet in running cold water for 10 seconds.
3. 5ml of conditioner formulation without hydrolysed quaternised protein cyclodextrin was massaged into the A swatch for1 minute.
4. 5ml of conditioner formulation without hydrolysed quaternised protein cyclodextrin was massaged into the B swatch for1 minute.
5. The hair swatches were rinsed under a running cold tap for 10 seconds.
6,: 6. The hair swatches were blotted dry on tissues.
7. The swatches were allowed to dry at ambient temperature and relative humidity for one hour.
8. The swatches were transferred to separate 5ml test tubes and methanol (HPLC grade, 5ml) added.
9. The test tubes were covered and the hair left for 30 minutes. . .
10. The hair swatches were removed and the methanol extracts analysed by Gas Chromatography under the following conditions: Gas ChromatoaraPhv analysis conditions
As in example 3.
Citral shows two peaks on GC analysis (due to cis and bans isomers). The amount of citral present in the methanol extracts was determined from the ratio of the peak area detected for each peak to the peak area obtained for a sample of citral in methanol of known concentration. Fragrance delivery values were calculated for each peak using the following equation: Percentage fragrance delivery = Weight of citral in the methanol extract x 100 Weight of citral in 5ml conditioner The fragrance delivery values for the two peaks obtained were averaged. The results are shown in table 4, with standard deviation (SD) values for each data point, and in figure 4.
Table 4: % fragrance delivery results for hair swatches treated with a conditioner containing quaternised hydrolvsed protein cyclodextrin derivative and control % fragrance delivery for a conditioner containing 3.23 quaternised hydrolysed protein cyclodextrin (1.07) % fragrance delivery for a conditioner without quaternised 2.06 hydrolysed protein cyclodextrin (0.64) The study demonstrates that the conditioner containing quaternised hydrolysed protein cyclodextrin derivative delivered the fragrance, citral, to hair to a greater extent than conditioner without quaternised hydrolysed protein cyclodextrin eeec' derivative Example 7: Measurement of the substantivity to hair of a hydrolysed protein cyclodextrin derivative according to Example 1 from shampoo and conditioner : systems Materials used in example 7 Virgin European brown hair (ex. De Meo Brothers) Basic shampoo base-10% water Basic hair conditioner -10% water Hydrolysed protein cyclodextrin derivative (as in example 1) 2% sodium lauryl ether sulphate (SLES) solution lodine'25 (Amersham Biosciences) Preparation of test solutions A 2.0Og sample of Protein Cyclodextrin derivative was radiolabelled using the Croda Chemicals Europe standard procedure.
Croda Chemicals Europe protein radiolabellinq procedure Materials: Solution 1 - Protein test solution.
Solution 2 -Solution 1 adjusted to pH 7.5 and diluted 1 in 10 in sodium phosphate buffer.
Solution 3 - 0.1% sodium iodide in pH 7.5 sodium phosphate buffer.
Solution 4 - Sodium phosphate buffer at pH 7.5 ( 0.25M NaH2PO4.2H2O [ 25. 359/ 500ml] + 0.25M Na2HPO4 [17.745g / 500ml] adjusted to pH 7.5 with NaOH).
Iodobeads (Perbio Science UK Ltd) lodine'25 (Amersham Biosciences) Procedure: 1) Rinse one iodobead with 5001 of buffer solution 4.
2) Open 1'25 vial and add 10OIll of buffer solution 4, mix for 30 seconds using pipette.
3) Add the buffer rinsed iodobead to the vial and close the vial.
4) Leave to stand for 2 minutes.
5) Open vial and add 1001 of diluted protein solution 2, mix for 30 seconds using pipette.
6) Close vial and allow to stand for 1 hour.
7) To a 1 Oml glass beaker containing magnetic flea add 2ml of protein solution : 1.
8) Place beaker on magnetic stirrer.
9) Open vial and remove reactant mixture by pipette and add to beaker.
10) Close vial.
11) Add 10OIll of sodium iodide solution 3 to beaker.
12) Cover beaker with lead shield.
13) Turn magnetic stirrer on for 5 minutes then turn off.
14) Set up ion-exchange column with 5 ml of resin IRA-94S in chloride form.
15) Rinse column with 200ml distilled water to remove residual chloride.
16) By pipette add 1'25 mixture to top of column.
17) lon-exchange at 1 ml/min and collect in 1 Oml volumetric flask washing mix through with distilled water to the 1 Oml mark to generate the test solution.
18) Count the test solution, 100111 3 times using different pipettes.
19) Store test solution in steel cabinet until ready for use.
The radiolabelled hydrolysed protein cyclodextrin derivative was added to formulations as detailed below to produce formulations containing 1% w/w hydrolysed protein cyclodextrin derivative as supplied.
Shampoo test solution % Basic shampoo base-10% water 90.0 Radiolabelled protein cyclodextrin derivative qs (to provide 1.0% as supplied) Distilled water upto 100 Conditioner test solution % Basic hair conditioner-10% water 90.0 Radiolabelled protein cyclodextrin derivative qs (to provide 1.0% as supplied) Distilled water up to 100 . Treatment of samples For each study, triplicate 1 OOmg hair swatches were used. The level of radiolabelled protein present on the hair swatches was measured after 1, 3 and 5 applications of the test solutions. Ail swatches were pre-washed in 2% SLES : solution, rinsed thoroughly and dried.
The treatment protocol was as follows: 1. Each hair swatch was immersed in water (10ml) for 60 seconds at 25 C.
2. Each hair swatch was dried by gently blotting between paper tissues.
3. Each hair swatch was immersed in 10ml of formulation under test for 60 seconds at 25 C, ensuring good and even contact.
4. Each hair swatch was removed from the test formulation and rinsed in 3 x 250ml water at 37 C; each rinse being for 30 seconds.
5. Each hair swatch was dried by gently blotting between paper tissues.
6. The radioactivity of each hair swatch was measured using a Gamma Counter.
Steps 3-5 were repeated 4 times to give five applications of each test formulation.
Further radioactivity measurements were taken after 3 and 5 applications of test formulation.
Results The substantivity results, for the treatment of virgin European brown hair with the shampoo and conditioner formulations are given in tables 5 and 6 respectively and in figure 5 below. The results show that a hydrolysed protein cyclodextrin derivative is substantive to virgin European brown hair from shampoo and conditioner formulations.
Table 5: Substantivitv (mo/1 OOq hair) on triplicate virgin hair swatches after shampoo treatments 1 - 5.
Treatments Tress 1 Tress 2 Tress 3 Mean SD 7.62 7.75 6.94 7.44 0.43 13.94 18.14 13.69 15.26 3.14 19.04 19.26 21.06 19.79 1.27 : . . 1 c . . : ' 5 : ' ' ': Table 6: Substantivitv (mq/1 OOq hair) on triplicate virgin hair swatches after conditioner treatments 1 - 5.
Treatments Tress 1 Tress 2 Tress 3 Mean SD 1 15.85 16.42 11.90 14.72 2.46 35.64 45.17 29.59 36.80 7.85 46.62 48.59 39.73 44.98 4.65 In summary, the invention comprises the following embodiments: 1. The preparation and use of protein-cyclodextrin derivatives for use in cosmetic compositions.
2. The use of a protein cyclodextrin derivative of (1) as a fragrance retention agent in hair and skin cosmetic formulations.
3. The use of a protein cyclodextrin derivative of (1) as a malodour control agent in hair and skin cosmetic formulations.
4. The use of a protein cyclodextrin derivative of (1) as a fragrance delivery agent in hair and skin cosmetic formulations.
5. A protein cyclodextrin derivative of (1) wherein a protein and reactive cyclodextrin are reacted in the range from 50% to 200% reactive cyclodextrin by weight of active protein. The resulting derivative thus comprises 33% to 66% cyclodextrin and modified reactive amino groups of the protein in the range 10 - 100%.
6. A protein cyclodextrin derivative of (1) wherein the protein cyclodextrin derivative is the reaction product of a protein hydrolysate and a reactive cyclodextrin.
7. A protein cyclodextrin derivative of (1) wherein the protein may be derived from either animal or vegetable sources or by fermentation.
8. A protein cyclodextrin derivative of (1) wherein the protein may be in the form :: . of a chemically modified protein (for example, quaternised) provided that some free amino groups are still present in the protein molecules.
9. A protein cyclodextrin derivative of (1) wherein the organofunctional cyclodextrin component may be any of the known cyclodextrins containing :' from six to twelve glucose units, especially alpha-cyclodextrin, beta cyclodextrin or gamma-cyclodextrin cyclodextrin, more especially beta cyclodextrin. The alpha cyclodextrin consists of six glucose units, the beta cyclodextrin consists of seven glucose units, the gamma cyclodextrin consists of eight glucose units 10. A protein cyclodextrin derivative of (1) wherein the average molecular weighs of the protein component may be from 150 Daltons (D) to 500 kD, is preferably within the range from 295D to 50kD and is more preferably in the range of from 295D to 25.5kD, even more preferably 350D to 3000D expressed as weight average molecular weight (Mw) derived from size exclusion chromatography.

Claims (37)

  1. Claims: 1. A protein-cyclodextrin derivative obtained by the reaction of a
    reactive cyclodextrin and a protein.
  2. 2. A protein-cyclodextrin derivative as claimed in Claim 1 having the general formula (I): [R -(NH)z]w - (Tb-C)p (I) wherein R'-(NH) is the residue of a hydrolysed protein R-NH2; T is the residue of an organofunctional group attached to cyclodextrin; C is cyclodextrin; b corresponds to the number of organofunctional groups on the reactive cyclodextrin and is preferably in the range 1 to 8; p corresponds to the number of organofunctional cyclodextrin reacted with amino groups on hydrolysed protein residues and will be preferably in the range of 1 to (w x z); z is the number of primary amine groups on the hydrolysed protein R'-NH2 available for reaction with the organofunctional cyclodextrin; w is the number of hydrolysed protein residues and is preferably in the range of 1 to (pxb).
  3. 3. A protein-cyclodextrin derivative according to Claim 1 or Claim 2 wherein R'-(NH) is the residue of a hydrolysed protein. :'
  4. 4. A protein-cyclodextrin derivative according to Claim 3 wherein the hydrolysed protein is a vegetable protein hydrosylate such as a hydrosylate derived from potato, wheat or soya protein, and preferably potato protein.
  5. 5. A protein-cyclodextrin derivative according to any preceding claim wherein a protein and a reactive cyclodextrin are reacted in the range of 50% to 200% reactive cyclodextrin by weight of active protein.
  6. 6. A protein-cyclodextrin derivative as claimed in any of Claims 2, or Claims 3 to 5 when dependent on Claim 2, wherein the group T comprises a residue of an organofunctional group selected from the group comprising: chloro-triazinyl, epoxides, acyl halides, sulphonyl halides, anhydrides and aldehyde groups.
  7. 7. A protein-cyclodextrin derivative as claimed in Claim 6 wherein the group T comprises a triazinyl group.
  8. 8. A protein-cyclodextrin derivative as claimed in any preceding claim wherein the protein moiety incorporates at least one quaternary ammonium group, providing that there is at least one unquaternised amino group in the protein to react with the reactive cyclodextrin.
  9. 9. A protein-cyclodextrin derivative as claimed in any preceding claim wherein the weight average molecular weight of the protein component is from 150 Daltons to 500KD.
  10. 10. A protein-cyclodextrin derivative as claimed in any preceding claim wherein the weight average molecular weight of the protein component is from 200D to : .' 50KD. . .
  11. 11. A protein-cyclodextrin derivative as claimed in any preceding claim wherein . the weight average molecular weight of the protein component is from 350D to :' 3000D.
    . . .
  12. 12. A protein-cyclodextrin derivative according to any preceding claim wherein the cyclodextrin component comprises a cyclodextrin containing from six to 12 glucose units, and preferably alpha-cyclodextrin, beta- cyclodextrin or gamma cyclodextrin or derivatives thereof.
  13. 13. A protein-cyclodextrin derivative according to any preceding claim having the general formula (111):
    OR
    OR O / /OR ROW RO) -< 0 (oOR ROo: (I I 1)
    TO FIR
    RO
    wherein: 40 8
    O 8 /
    8 8. NO /} \\ 888 R=Hor I/ N : \ I N=<, 8 NHR' 8 8 4 and R'-NH is the residue of a hydrolysed protein.
  14. 14. An inclusion complex formed from a protein-cyclodextrin derivative as claimed in any preceding claim wherein the guest molecule(s) in the cavity of the cyclodextrin is a fragrance.
  15. 15. The use of a protein-cyclodextrin derivative in a cosmetic composition.
  16. 16. The use according to Claim 15 wherein the cosmetic composition is a hair care composition.
  17. 17. The use according to Claim 15 wherein the cosmetic composition is a skin care composition.
  18. 18. The use of a protein-cyclodextrin derivative as a fragrance retention agent.
  19. 19. The use according to Claim 18 wherein the fragrance retention agent is used in a cosmetic composition such as a hair care or a skin care composition.
  20. 20. The use of a protein-cyclodextrin derivative as a malodour control agent.
  21. 21. The use according to Claim 20 wherein the malodour control agent is used in a cosmetic composition such as a hair care or a skin care composition.
  22. 22. The use of a protein-cyclodextrin derivative as a fragrance delivery agent.
  23. 23. The use according to Claim 22 wherein the fragrance delivery agent is in a cosmetic composition such as a hair care or a skin care composition.
    . . *
  24. 24. The use according to any of Claims 15 to 23 inclusive wherein the protein- cyclodextrin derivative has the general formula (I): * [R-(NH)z]w (Tb-C)p (1) l, c, wherein R'-(NH) is the residue of a hydrolysed protein R'-NH2; T is the residue of an organofunctional group attached to cyclodextrin; C is cyclodextrin; b corresponds to the number of organofunctional groups on the reactive cyclodextrin and is preferably in the range 1 to 8; p corresponds to the number of organofunctional cyclodextrin reacted with amino groups on hydrolysed protein residues and will be preferably in the range of 1 to (w x z), z is the number of primary amine groups on the hydrolyses protein R'-NH2 available for reaction with the organofunctional cyclodextrin; w is the number of hydrolyses protein residues and is preferably in the range of 1 to (p x b) .
  25. 25. The use according to Claim 24 wherein R'-(NH) is the residue of a hydrolyses protein.
  26. 26. The use according to Claim 25 wherein the hydrolysed protein is a vegetable protein hydrosylate such as a hydrosylate derived from potato, wheat or soya protein, and preferably potato protein.
  27. 27. The use according to any of Claims 15 to 26 inclusive wherein a protein and a reactive cyclodextrin are reacted in the range of 50% to 200% reactive cyclodextrin by weight of active protein.
  28. 28. The use according to Claim 24 or Claims 25 to 27 when dependent on Claim 24 wherein the group T comprises a residue of an organofunctional group selected from the group comprising: chloro-triazinyl, epoxides, acyl halides, sulphonyl halides, anhydrides and aldehyde groups.
    I F
  29. 29. The use according to Claim 29 wherein the group T comprises a triazinyl group. .
  30. 30. The use according to any of Claims 15 to 29 inclusive wherein the protein moiety incorporates at least one quaternary ammonium group, providing that there is at least one unquaternised amino group in the protein to react with the reactive cyclodextrin.
  31. 31. The use according to any of Claims 15 to 30 inclusive wherein the weight average molecular weight of the protein component is from 150 Daltons to 500KD.
  32. 32. The use according to any of Claims 15 to 31 inclusive wherein the weight average molecular weight of the protein component is from 200D to 50KD.
  33. 33. The use according to any of Claims 15 to 32 inclusive wherein the weight average molecular weight of the protein component is from 350D to 3000D.
  34. 34. The use according to any of claims 15 to 33 inclusive wherein the cyclodextrin component comprises a cyclodextrin containing from six to 12 glucose units, and preferably alpha-cyclodextrin, beta-cyclodextrin or gamma-cyclodextrin or derivatives thereof.
  35. 35. The use according to any of Claims 15 to 23 inclusive wherein the protein cyclodextrin derivative has the general formula (111):
    OR
    OR O / _:0/O (IIl)RO O 1< OR RO
    OR JO
    1 1 8 1 1 161; wherein: RO
    O
    R=Hor / N
    NO NHR'
    and R'-NH is the residue of a hydrolysed protein.
  36. 36. A hair care composition incorporating a protein-cyclodextrin derivative or an inclusion complex as claimed in any of Claims 1 to 14 inclusive.
  37. 37. A skin care composition incorporating a protein-cyclodextrin derivative or an inclusion complex as claimed in any of Claims 1 to 14 inclusive. :'
    # # .
GB0411872A 2004-05-27 2004-05-27 Reactive cyclodextrins derivatised with proteins Withdrawn GB2414479A (en)

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PCT/GB2005/002123 WO2005116085A1 (en) 2004-05-27 2005-05-27 Protein-cyclodextrin derivatives

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FR3006315B1 (en) 2013-05-31 2015-10-02 Centre Nat Rech Scient COMPATIBLE SELF-ASSOCIATIVE MICROPARTICLES AND NANOPARTICLES OF PROTEINS
FR3011470B1 (en) 2013-10-09 2017-01-06 Centre Nat De La Rech Scient (Cnrs) ANTIFUNGAL COMPOSITION COMPRISING AN ANTIFUNGAL AGENT AND HYDROPHOBIC CHITOSAN
CN110204739B (en) * 2019-05-06 2020-10-27 北京化工大学 Preparation of silk fibroin-based self-healing or/and conductive hydrogel

Citations (6)

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Publication number Priority date Publication date Assignee Title
US5068227A (en) * 1989-01-18 1991-11-26 Cyclex, Inc. Cyclodextrins as carriers
WO2000040962A1 (en) * 1998-12-30 2000-07-13 Kosak Ken M Cyclodextrin polymers for use as drug carriers
WO2001026617A1 (en) * 1999-10-08 2001-04-19 Coty B.V. Cosmetic preparation of active substances with a synergistically increased radical protection factor
US6436414B1 (en) * 1999-09-02 2002-08-20 Beiersdorf Ag Active ingredient combinations or adducts of biotin and/or biotin derivatives and cyclodextrins and use of such active ingredient combinations in cosmetic preparations
US20030040008A1 (en) * 2000-04-14 2003-02-27 Arc Seibersdorf Research Gmbh Method for lmmobilizing an analyte on a solid surface
WO2003026603A1 (en) * 2001-09-21 2003-04-03 Beiersdorf Ag Cosmetic and/or dermatological active ingredient combination of triterpenes and cyclodextrins

Family Cites Families (1)

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Publication number Priority date Publication date Assignee Title
DE4429229A1 (en) * 1994-08-18 1996-02-22 Consortium Elektrochem Ind Cyclodextrin derivatives with at least one nitrogen-containing heterocycle, their production and use

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5068227A (en) * 1989-01-18 1991-11-26 Cyclex, Inc. Cyclodextrins as carriers
WO2000040962A1 (en) * 1998-12-30 2000-07-13 Kosak Ken M Cyclodextrin polymers for use as drug carriers
US6436414B1 (en) * 1999-09-02 2002-08-20 Beiersdorf Ag Active ingredient combinations or adducts of biotin and/or biotin derivatives and cyclodextrins and use of such active ingredient combinations in cosmetic preparations
WO2001026617A1 (en) * 1999-10-08 2001-04-19 Coty B.V. Cosmetic preparation of active substances with a synergistically increased radical protection factor
US20030040008A1 (en) * 2000-04-14 2003-02-27 Arc Seibersdorf Research Gmbh Method for lmmobilizing an analyte on a solid surface
WO2003026603A1 (en) * 2001-09-21 2003-04-03 Beiersdorf Ag Cosmetic and/or dermatological active ingredient combination of triterpenes and cyclodextrins

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