Cosmetic compositions containing cyclic dipeptide compound
FIELD: medicine; cosmetology.
SUBSTANCE: invention contains antiperspirant, continuous phase and structure-forming agent containing cyclic depeptide derivative, method of production thereof, method of hidropoiesis prevention or reduction, derivative of cyclic depeptide and gel base for antiperspirant.
EFFECT: compositions have higher activity.
46 cl, 10 tbl, 6 ex
The SCOPE TO WHICH the INVENTION RELATES
The present invention relates to cosmetic compositions for application to human skin, to the preparation and use of such compositions and to a structure of substances for inclusion in such compositions and their receipt.
The BACKGROUND TO the INVENTION AND SUMMARY of the PRIOR art
Many cosmetic compositions for application to human skin is used structured carrier liquid for delivery of coloring or some other active substances to the skin surface. The main examples of such cosmetic compositions include compositions of antiperspirants or deodorants that are widely used to avoid or minimize the appearance of wet areas on the skin, especially in the armpit, or to control or prevent release an unpleasant odor, which could otherwise occur when the sweating. Other examples of cosmetic compositions include lipsticks.
Although structured programming is a concept often used in relation to substances, structuring the carrier fluid (liquid media), you can also use various other terms, including curing and gelation.
Antiperspirant or dezodoriruyuschee compositions p who was illegalise in the form of various products. One of them is the so-called "pencil", which is usually a rod apparently solid substance, held in the distribution container, and which retains its structural integrity and shape during use. In this respect, they represent a cosmetic composition in the form of a pencil containing other active ingredients. When part of the rod is carried out on the surface of the skin, the film compositions of the rod is transferred to the surface of the skin. Although the rod has the form of a solid object, is able to maintain its own form within a period of time, this substance is often structured liquid phase, so that the film composition can be easily transferred from the rod to another surface upon contact.
Pencils-antiperspirants can be divided into three categories. Suspension pencils contain particulate antiperspirant active substance suspended in a structured liquid phase carrier, which often is anhydrous and/or in many cases may be immiscible with water. Emulsion pencils usually have a hydrophilic phase mainly containing the active ingredient is an antiperspirant in solution, this phase forms an emulsion with the second, more hydrophobic liquid phase. The continuous phase of the emulsion is structureyou is Noah. Restoredatabase pencils are usually active ingredient is an antiperspirant, dissolved in a structured liquid phase, which is polar and can contain a polar organic solvent which is miscible with water, and the polar phase may contain water.
There is a solid literature on structuring cosmetic compositions, for example compositions of antiperspirants or deodorants.
Usually, many of the "pencils" structured with the use of natural or synthetic waxy substances, the concept of which include substances like beeswax so that they gradually soften with increasing temperature, until will not become a liquid, typically at about 95°C. Examples of structured wax "pencils" described in the article in Cosmetics and Toiletries, 1990, Vol 105, P75-78, U.S. patent 5169626 and 4725432 and in many other publications, some of them such substances referred to as hardening agents.
More specifically, in normal practice, "pencils" structured or utverjdali inclusion in the composition of fatty alcohols, often accompanied by castor wax. "Pencils", structured fatty alcohols, leave visible white deposits when applied to human skin; moreover, these attacks can be carried on clothing when account is the skin, and you can, for example, to detect white marks on the armhole of the garment without sleeves. Fatty alcohols are often considered as included in the General category waxy substances, but we noted that they are a more significant source of white attacks than various other waxy substances.
It was suggested several alternative waxy substances structuring or curing agents. For example, using dibenzylidene sorbitol (DBS) or its derivatives as geleobrazovanie for polar or hydrophilic liquid carrier has been proposed in several publications such as EP-A-512770, WO-92/19222, US 4954333, US 4822602 and US 4725430. Compositions containing such geleobrazovanie can have a number of disadvantages, including instability in the presence of acidic antiperspirant and relatively high processing temperatures required for the production of "pencils".
Other alternative proposed structuring substances include various classes of esters or amides, which are solid at ambient temperature and is able to be cured hydrophobic or water-immiscible carrier liquid. One class of such compounds include ester or amide derivatives of 12-hydroxystearate acid, described, inter alia, in US-A-5750096. Another class of such esters or am the Dov include amides and esters of N-acylaminoalkyl, of which di-n-butylamide N-Lauroyl-L-glutamic acid commercially available from Ajinomoto under the name GP-1. They are described in U.S. patent 3969087. Another class that might be exposed to as gel-forming substances include amide derivatives of two - and trekhosnovnykh carboxylic acids described in WO 98/27954, especially alkyl N,N'-dialkyl succinamide. Another amide structure of matter for water-immiscible liquid carriers are described in EP-A-1305604.
Although many amido-structuring substances have already been identified, the task is to classify others who can meet the rigorous standards of the beauty industry and to improve or eliminate one or more of the difficulties or disadvantages associated with various amido-structuring substances that have already been proposed or used.
The following class of compounds containing the-CO-NH - group, includes cyclopeptide, which are cyclic derivatives of amino acids. Various cyclopeptide were described in the article by K. Hanabusa et al, entitled "Cyclo(dipeptide)s as low molecular-mass Gelling Agents to harden Organic Fluids", J. Chem Soc. Commun., 1994, pp l401/2. These cyclopeptide satisfy the General formula
in which R1and R2mean organic radicals. The selection is illustrated to include two prophetic is Tami (8 and 9), in which R1was a complex alkylether representing or-CH2CO2CH2CH2CH2Me, or-CH2CO2CH2CH2CHMeCH2CH2CH2CHMe, and R2represented-CH2Ph. This document here called Hanabusa I.
In this introduction Hanabusa says that the most difficult problem to obtain a gelling agent with a low molecular weight is the stabilization of the formed gel, in other words, how to prevent the transformation of an unstable gel in the crystalline state. After spending an extensive amount of research in the field of gels formed by the use of geleobrazovanie with low molecular weight, Applicants can confirm that stabilization of such gels is often really serious and difficult problem, and, in fact, a problem that can be compounded in the cosmetic compositions of the presence of other cosmetic ingredients. Hanabusa I subsequently makes a General statement that educated gels (in this case using cyclopeptides illustrated in the list of organic liquids listed in Table 1) were stable even after several months.
Various other cyclo(dipeptides)satisfying the formula 1, above, were described in another article Hanabua et al., called "Low Molecular Weight Gelators for Organic Fluids: Gelation using a Family of Cyclo(dipeptide)s", Journal of Colloid and Interface Science 224, 231-244 (2000), named here Hanabusa II. This text describes the substance No. 22-28, which were more esters, such substances 8 and 9 in Hanabusa I, except that they were obtained from different alcohols. Applicants have found that such esters, and, in particular, of the 27 and 28 in Hanabusa II, obtained gels are not stable.
Applicants have tested a number of substances as geleobrazovanie in oils, which are common in the cosmetic compositions according to the Formula 1 in Hanabusa I, II-27 and II-28, which seemed to be the best geleobrazovanie according Hanabusa. Unfortunately, the resulting products showed poor performance storage at an ambient temperature of the laboratory. The applicants concluded that, at best, the ability of cyclopeptides to sustainable gelation of organic liquids might change significantly depending on the chemical nature of a substitute radicals R1and R2.
The number of derivatives of cyclic dipeptides was described as geleobrazovanie in Japanese Kokai No 2001-247451, on behalf of Pola Chemical Industries Inc Nisshin Oil Mills Ltd. There were either alkyl derivatives, which have already been described Hanabusa, or the unsubstituted College the strong derivative, which probably showed poor stability when tested in the same way as derivatives, proposed Hanabusa.
SUMMARY of the INVENTION
Currently, Applicants have found that the selected derivatives cyclopeptides can be used as structuring agents for cosmetic compositions. When using a moderate percentage of the composition, usually not more than 15% by weight and often less than 10% by weight, they are able to structure the composition such that it will exceed that achieved substances II-27 and II-28 y Hanabusa. Indeed, at the same time, and where appropriate, the composition can give coverage no worse than the rest with low visibility. It should be noted that the derivatives of cyclopeptides here alternative can be called diketopiperazine derivatives.
The present invention is the creation of structured cosmetic compositions in which the liquid carrier is structured using a structure of substances, other than those referred to above. Another objective of this invention is to provide a structure of substances, which can show properties that exceed at least the structural properties of substances II-27 and II-28 y Hanabusa, certain to enter the.
Another objective of certain embodiments of this invention is to provide compositions that have low visibility coverage, i.e. give a seamless finish.
It was found that the properties of the gels in the hydrophobic liquid carriers can be improved by the esterification of cyclo(dipeptide)acid alcohol, to obtain a cyclic residue.
In General, in the first aspect of the present invention features a cosmetic composition containing:
i) a substance with antiperspirant activity,
ii) a continuous phase which contains a water-immiscible carrier liquid, and
iii) structuring a substance that contains cyclopeptide derivative having the General formula
in which RArepresents a carbocyclic or heterocyclic group containing not more than 2 rings, in addition to unsubstituted cyclohexyl.
Such cyclopeptide connections here are sometimes referred to as DOPA derivatives or DOPAD, and radical, containing cyclopeptide and carboxyl group, here is sometimes called DOPA residue.
For the avoidance of doubt, used here DOPA derivative, a cyclic group in RAdirectly related to DOPA radical.
DOPA derivative, as described above, serves as structural materials for nesma is ivyselect water liquid media and when used in an appropriate amount, which preferably is less than 15% of the total composition, is able to structure the liquid in the gel with a stiffness sufficient to preserve his own form.
The applicant has found that the structure of the substances used in this invention, to form fibers or filaments in the liquid phase.
Not being tied to any particular theory or explanation, the Applicant believes that the formation of the gel network is formed of such fibers, which is distributed throughout the liquid phase. By heating the gel to the melting temperature of the gel yarn texturing compounds are dissolved, and the liquid phase becomes more mobile.
To maintain good sensory properties during use, it is preferable to include silicone oil, at least as a fraction of water-immiscible liquid carrier. The amount of silicone oil may be at least 10% by weight of the composition and/or at least 25% by weight of water-immiscible liquid carrier.
Fatty alcohol that is solid at a room temperature of 20°C, such as stearyl alcohol, lead to opaque white in appearance raids and, preferably, essentially absent, this implies the presence of not more than 3% by weight of the composition, more preferably, less than 1% and most preferably 0%. the AK mentioned, fatty alcohols are often considered as included in the General class waxy substances. In a General sense the term "wax" is usually applied to various substances or mixtures (including some fatty alcohols), which have some differences in chemical structure, but similar in their physical properties. This term basically means substances which are solid at 30°C, also often hard to 40°C, waxy in appearance or touch, but which gradually soften and eventually melt to low-viscosity liquid at a temperature below 95°C, usually below 90°C.
Perhaps this composition does not include more than 3% of any substance, which is a wax that is solid at 30°C, but razmyagchayuschiesya at elevated temperature and at 95°C melted and dissolved in water-immiscible liquids, which also are not able to form a network of fibres in the composition when cooled to 20°C.
As will be explained in more detail below, here in the cosmetic compositions of structured water-immiscible carrier fluid may be a continuous phase in the presence of a dispersed second phase, which may contain a suspension of particles of a solid substance, forming a suspension pencil, or dispersion of droplets lipofuze fluid. This solid substance may is set loose antiperspirant or deodorant active substance or pigment. This dispersed liquid phase may contain a solution of the above-mentioned active substances or active substances in water or other hydrophilic, i.e. lipophobia, solvent.
An additional advantage of the preferred structure of the substances according to this invention is that the gel, which they form, are physically more stable, both during the process and the resulting compositions, compared with geleobrazovanie II-27 and II-28 y Hanabusa.
The composition according to this invention will be mainly sold in the container through which it can be applied during use. This container may be of the usual type.
The second aspect of the present invention, therefore, offers a cosmetic product containing a distribution container having an aperture for delivery of the contents of the container, means for pushing the contents of the container through the hole and composition according to the first aspect of the present invention in this container.
Means for loading the contents of the container in the specified hole or holes for the passage through them, can be movable part which operates the user, or the nozzle in the container opposite the hole with access for fingers.
Songs and on this invention can be manufactured by conventional manufacturing methods cosmetic solids.
Thus, in accordance with a third aspect of the present invention features a method of manufacturing a cosmetic composition, comprising the stage of:
ai) the introduction of water-immiscible liquid carrier structure of a substance is one or more structures of the compounds defined in the first aspect,
a2) mixing the liquid carrier with solid or dispersed liquid phase containing a cosmetically active substance in the form of particles or dissolved, suspended in a water-immiscible liquid,
a3) heating a liquid medium or a mixture containing it, to the elevated temperature at which the structure forming substance is dissolved or dispersed in water-immiscible liquid carrier,
stage a1), a2) and a3) are performed in any order followed:
b1) introducing the mixture into a form, which, preferably, is a distribution container, and then
c1) cooling or by cooling the mixture to a temperature at which the solidified liquid media.
Suspended solids can be any cosmetically active substance that at least partially insoluble in lipophilic water-immiscible liquid carrier included in the number, and the dispersed liquid phase can be p is the target of such an active substance in a hydrophilic or polar solvent.
In the fourth aspect of the present invention, the cosmetically active substance contains antiperspirant or deodorant active ingredient. In accordance with the fourth aspect, a cosmetic method for preventing or reducing perspiration or create a fragrance on the skin, which includes the local application to the skin of a composition containing an antiperspirant or deodorant active substance, water-immiscible carrier liquid and structuring substance as defined above in the first aspect.
In the fifth aspect of the present invention offers a new ester derivatives of DOPA in accordance with the General formula given in the first aspect.
In the sixth aspect of the present invention proposes a method of obtaining new esters according to the fifth aspect, in which DOPA acid is reacted with at least equimolar amount of an alcohol of formula RAOH in the presence of at least 0.5 moles of activator per mole DOPA acid in the reaction medium containing dimethyl sulfoxide.
DETAILED DESCRIPTION AND IMPLEMENTATION OPTIONS for
As mentioned above, in accordance with the first aspect, the present invention requires structuring the substance in the water-immiscible liquid phase. There also may be other substances depending on the nature to which notizie. Will now be examined in turn various substances and will indicate the preferred features.
Structure of matter of the present invention satisfy the General formula:
in which RArepresents a carbocyclic or heterocyclic group containing not more than 2 rings, in addition to unsubstituted cyclohexyl.
Preferably, the carbocyclic or heterocyclic group in RAsubstituted by at least one alkyl, ether or ester substituent and/or contains at least one unsaturation of the ring. Unsaturated rings may result in non-aromatic group, for example containing 1 or 2 degrees of unsaturation or aromatic group. Although the gels were prepared using a derivative in which RAis unsubstituted tsiklogeksilnogo group, they are relatively unstable during storage under normal storage conditions, the stability can be improved by allocating one or more substituents around tsiklogeksilnogo group or the introduction of unsaturation or heteroatoms.
Here RAcan contain two condensed rings, but preferably contains a single six-membered ring or a carbocyclic or heterocyclic, or ring the internal bridge. In those cases where RAndis carbocyclic, it can be either saturated or unsaturated, preferably unsaturated, or aromatic. In those cases where RAndis heterocyclic, it is preferably saturated.
Although the cyclic group in RAmay be unsubstituted, except cyclohexyl, it is preferably substituted by at least one alkyl Deputy, which preferably contains not more than 16 carbon atoms. In some particularly preferred embodiments, the implementation of the alkyl substituent has the longest chain of up to 4 carbon atoms, and in some cases the total carbon content of up to 5 carbon atoms. Alkyl substituent may be linear or branched. Preferred examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl or t-butyl or isopentyl. In a series of particularly suitable derivatives of DOPA, RAcontains two or more alkyl substituents and especially those selected from the above list of preferred examples. Alkyl substituents may be the same, for example two or more methyl substituents, or may be a combination of different substituents, such as methyl and isopropyl substituents. In those cases where RAis saturated, C is mstiteli can be one and the same carbon atom in the ring, for example, two methyl groups, or different carbon atoms. In several particularly desirable derivatives, two alkyl substituent is meta or para relative to each other, for example meta methyl group or pair methyl and ISO-propyl group. In some derivatives, the ring may include a methylene bridge, which preferably also completes a six-membered ring.
In some suitable DOPA derivatives one alkyl substituent may be ortho or para with respect to communication with DOPA radical, as in 4-methyl-phenyl-. In some or other DOPA derivatives connection with DOPA radical is in the meta position with respect to one or preferably two methyl deputies.
In those cases where RAis heterocyclic, suitable heterocyclic atom is nitrogen. Conveniently, when the heterocyclic atom may be in the para position with respect to communication with DOPA radical. Moreover, in the row of the desired derivatives heteroatom is in the ortho position with respect at least one alkyl group, preferably in a saturated ring, and especially to the ortho methyl groups up to 4.
RAit is often easier just to call a radical from the corresponding alcohol, which can react with DOPA with the formation of ester bonds. Therefore, we wish the examples R Ainclude radicals of 4-alkylphenol, for example 4-nonyl-phenol, and 2,6-dialkyl - or 2,2,6,6-tetraalkyl-4-piperidinol, for example 2,2,6,6-tetramethyl-4-piperidinol.
In some particularly preferred DOPA derivatives ring in RAis carbocyclic and substituted by at least two alkyl groups, of which at least one represents methyl and the other, or one of the others, represents isopropyl. Examples of such RAradicals include menthol, thymol, isopinocampheol and 3.5-dealkilirovania, for example 3,5-dimethylcyclohexane. Particularly preferably, methyl group is in the para position relative to the isopropyl group, as derived from carvacrol. Particularly suitable is DOPAD from thymol, due to its ability to form a solid, transparent and stable "pencils".
Although many suitable DOPAD compounds described herein, substituted alkyl Deputy or deputies, at least one of the substituents may itself be an ethylene unsaturated, i.e. contain alkenylphenol group, which in many cases contains from 2 to 6 carbon atoms. Suitable examples include isopropanol and Isobutanol. Such unsaturated group may be used instead of the corresponding saturated alkyl groups containing the same Chi is lo carbon atoms, as explained above. One suitable DOPAD compound contains derived from carveol.
In other compositions DOPAD the connection can be replaced by simple or complex ether, in particular this refers to aromatic derivatives, such as esters of benzoic acid. Such esters typically contain up to 10 carbon atoms in the ester substituent. Suitable DOPAD group containing ester Deputy, include ethylbenzoic, butylbenzoate and hexylbenzoate.
DOPA derivatives used in this invention may be a mixture of compounds within this General formula, or can be an individual connection.
Data DOPA derivatives can be obtained by reaction of the corresponding alcohol with DOPA in the form of acid (DOPAA), or perhaps with the acid chloride, or possibly anhydride or a complex ester containing DOPA radical. DOPAA can be obtained by cyclization of aspartame.
The specified number of DOPA derivatives in the compositions of this invention may be from 0.1 to 15% by weight of the composition and preferably from 0.1 to 10%, and usually at least 0.3% and in many cases not more than 5%. In some particularly preferred embodiments, the implementation of a number of DOPA structuring substance constitutes from 0.5% to 3.5%. Here, unless otherwise indicated, % contents presents the mass calculated on the whole composition. If the composition is an emulsion with a separate dispersed phase, the number of structures(its) of the substances(a) may be from 0.15 to 20% by weight of the continuous phase, more likely, from 0.4% to 8% of this phase. In some particularly preferred embodiments, the implementation of the hydrophobic phase of the carrier contains from 1.5 to 4.5% DOPAD by weight, in the calculation of this phase. It should be noted that DOPA structuring of matter of this invention are particularly useful because they are able to form solid gels even at low concentrations structuring substances. This is advantageous not only because of the lower cost structure of a substance, often a relatively expensive component, but also due to the release site in the membership to include other desired components in the composition and reduce the number of components that can contribute to the visible raids. The use of fewer structural substances can also help during the preparation of gel-like compositions, offering more flexibility during the formation of the carrier liquid with well dispersed or dissolved gel.
The carrier fluid
Water-immiscible carrier fluid contains a single substance or mixture of substances, which are relatively hidrovo the tion, so as not to be mixed with water. In the media may be included with some hydrophilic liquid, provided that all the mixture in a carrier fluid immiscible with water. In General, it will be desirable that this carrier was a liquid (in the absence of structural substances) at a temperature of 15°C and above. She may have some volatility, but the pressure of its vapour will be mostly less than 4kpa (30 MND) at 25°C, so that the substance could be called the oil or mixture of oils. More specifically, it is desirable that at least 80% by weight of a hydrophobic liquid carrier would consist of substances with a vapour pressure not exceeding this value 4kpa at 25°C.
Preferably, the hydrophobic substance is a carrier comprised of volatile liquid silicone, i.e. liquid polyorganosiloxane. For a class "volatile" this matter should have moderate vapor pressure at 20 or 25°C. Typically, the vapor pressure of the volatile silicone is in the range from 1 or 10 PA to 2 kPa at 25°C.
It is desirable to include volatile silicone, because it gives the sensation of a "drier" for the applied film after application of the composition on the skin.
Volatile polyorganosiloxanes can be linear or cyclic or mixtures thereof. Preferred cyclic siloxanes include polydimethylsiloxane and, in particular containing from 3 to 9 and the Ohm silicon and preferably, not more than 7 silicon atoms and, most preferably, from 4 to 6 silicon atoms, otherwise often called cyclomethicone. Preferred linear siloxanes include polydimethylsiloxane containing from 3 to 9 silicon atoms. Volatile siloxanes are usually by themselves exhibit a viscosity below 10-5m2/s (10 Centistokes) and, in particular above 10-7m2/s (0.1 Centistokes), linear siloxanes typically exhibit a viscosity of less than 5 x 10-6m2/s (5 Centistokes). Volatile silicones may also contain branched, linear or cyclic siloxanes, such as the aforementioned linear or cyclic siloxanes substituted with one or more lateral-O-Si(CH3)3groups. Examples of commercially available silicone oils include oils having the class marking 344, 345, 244, 245 and 246 from Dow Corning Corporation; Silicone 7207 and Silicone 7158 company Union Carbide Corporation and SF1202 company General Electric.
Hydrophobic medium used here in the compositions may alternatively or additionally contain non-volatile silicone oils, which include polyalkylene siloxanes, polyalkylene siloxanes and polyethylsiloxane copolymers. They respectively can be selected from Dimethicone and dimethiconol of sipolilo. Commercially available non-volatile silicone oil on the Ute in products, available under the trademarks of the series Dow Corning 556 and Dow Coming 200. Other non-volatile silicone oils include oils under the trademark DC704. The inclusion of at least a certain amount of non-volatile silicone oil having a high refractive index, for example greater than 1.5, for example at least 10% by weight (preferably at least 25% to 100% and in particular from 40 to 80%) silicone oils, it is often useful in some compositions, as it facilitates the conversion to comparable values of the refractive indices of the components of the composition and, consequently, easier to create a transparent or translucent compositions.
Water-immiscible carrier liquid may contain from 0% to 100% by weight of one or more liquid silicones. Preferably, the liquid silicone is sufficient to ensure at least 10%, better at least 15%, by weight of the entire composition.
Hydrophobic liquid without silicon can be used instead of, or, more preferably, in addition to liquid silicones. Hydrophobic organic liquid without silicon, which can be included, comprise liquid aliphatic hydrocarbons such as mineral oil or hydrogenated polyisobutene, often chosen for the manifestation of low viscosity. The following examples of liquid hydrocarbons are n lidacenu and paraffins and ISO with at least 10 carbon atoms.
Other suitable hydrophobic carriers include liquid aliphatic or aromatic esters. Suitable aliphatic esters contain at least one alkyl group with a long chain, for example, esters derived from C1-C20alkanols, esterified With8-C22alanovoy acid or With6-C10escandinavo acid. Alcohol or acid portion of the molecule, or mixtures thereof, preferably selected so that each of them has a melting point below 20°C. Such esters include isopropylmyristate, laurierated, isopropyl, di-isopropylcarbonate and di-isopropylacetate.
Suitable liquid aromatic esters, preferably having a melting point below 20° (C) include fatty alkylbenzoates. Examples of such esters include the appropriate8-C18alkylbenzoates or mixtures thereof, including, in particular, With12-C15alkylbenzoates, for example available under the trademark Finsolv. The inclusion of alkylbenzoates as at least part of the hydrophobic carrier fluid can be useful because they can increase average (refractive index - TRANS) media containing volatile silicone, and thereby to simplify obtaining a transparent or translucent compositions.
The trail is either examples of suitable hydrophobic carriers include liquid aliphatic ethers, received at least one fatty alcohol, such as derivatives miristinovoi ether, for example PPG-3 ministerului ether or lower alkyl ethers of polyglycols, such as ether, called PPG-14 butyl ether by CTFA.
Can be used aliphatic alcohols, liquid at 20°C, and particularly preferably be used those which are immiscible with water. They include alcohols branched chain of at least 10 carbon atoms, such as isostearoyl alcohol and octyldodecanol. Such alcohols can contribute to the formation of a solution of DOPA derivatives in water-immiscible liquid carrier during the production of structured gels. Such alcohols can often be at least 10% or 15% by weight of water-immiscible mixture of a liquid medium, in many desirable mixtures can contain up to 70% or 80% of the mixture. In a series of suitable compositions, the proportion of such aliphatic alcohols in the above-mentioned mixture is from 10 or 15% to 30% by weight and in some other proportion is more than 30 mass%.
However, aliphatic alcohol that is solid at 20°C, usually linear alcohols, such as stearyl alcohol, preferably absent or present not more than 3% by weight of the entire composition, as indicated earlier, because they lead to a marked white fly when IU is coherent applying the composition to the skin.
Liquid, free from silicon which can range from 0-100% water-immiscible liquid carrier, but preferably, attended silicone oil, and that the number of components that are free from silicon, preferably up to 50 or 60% and even up to 80% of water-immiscible liquid carrier and in many cases from 10 to 60% by weight, for example from 15% to 30% or from 30%to 60%, by weight of the carrier liquid.
Liquid dispersed phase in the emulsion
If the composition is an emulsion, in which DOPA derivative acts as a structural substance in a hydrophobic continuous phase, the emulsion will contain more polar or lipophobia dispersed phase. The dispersed phase may be a solution of the active component.
Hydrophilic dispersed phase in the emulsion usually contains water as a solvent and may contain one or more water soluble or miscible with water, liquids in addition to or instead of water. The fraction of water in the emulsion in accordance with the present invention often chosen in the range of up to 60%, and in particular from 10% to 40% or 50% of the total composition.
One class of water-soluble or miscible with water liquids include monohydroxy alcohols, short-chain, for example from C1With4and, especially, ethanol or isopropanol, which can in order to give the composition deodorizing properties. When applied to the skin ethanol gives a cooling effect, because it is very volatile. It is preferable that the content of ethanol or any other monohydroxy alcohol with a vapor pressure above a 1.3 kPa (10 MND) did not exceed 15%, better not more than 8%, by weight of the composition.
The following class of hydrophilic liquids includes diols or polyols, preferably having a melting point below 40°C, or mixed with water. Examples of water-soluble, or miscible with water, liquids with at least one free hydroxyl group include ethylene glycol, 1,2-propylene glycol, 1,3-butyleneglycol, hexyleneglycol, diethylene glycol, dipropyleneglycol, 2-ethoxyethanol, onomatology ether of diethylene glycol, onomatology ether of triethylene glycol and sorbitol. Particularly preferred are propylene glycol and glycerin.
In the emulsion of the dispersed phase, probably, is from 5 to 80 or 85% by weight of the composition, preferably from 5 to 50, or 65%, more preferably from 25 or 35% up to 50 or 65%, while the continuous phase containing a structuring agent, here gives the balance of 15% or 35% up to 95% by weight of the composition. Can be useful compositions with a high proportion of the dispersed phase, i.e. from 65 to 85% of the dispersed phase, as they can give good hardness, even though to the focus structure of the substance can be only in a small proportion with the whole composition. However, compositions with a low proportion of the dispersed phase can also be useful because they give a feeling of warmth and dryness.
Emulsion composition generally will contain one or more emulsifying surfactants which may be anionic, cationic, zwitter-ionic and/or nonionic surfactants. The proportion of emulsifier in the composition is often selected in the range up to 10% by weight and, in many cases, from 0.1 or 0.25 up to 5% by weight of the composition. The most preferred amount is from 0.1 or 0.25, up to 3% by weight. Nonionic emulsifiers are often classified according to the HLB value (hydrophilic-lipophilic balance). It is desirable to use an emulsifier or mixture of emulsifiers with an overall HLB value in the range of 2 to 10, preferably from 3 to 8.
It may be convenient to use a combination of two or more emulsifiers having different HLB values above and below the desired value. Using two emulsifier together in the appropriate ratio, it is possible to easily achieve the average mass of HLB values, which leads to the formation of the emulsion.
Many suitable emulsifier with a high HLB are non-ionic ester or ether emulsifiers containing polyoxyalkylene part, especially polyoxyethylene part, often containing the t 2 to 80, and, mainly, from 5 to 60 oxyethylene units, and/or contain polyhydroxylated connection, such as glycerol or sorbitol or other aldit as the hydrophilic part. The hydrophilic part may contain polyoxypropylene. Emulsifiers optionally contain a hydrophobic alkyl, alkenylphenol or aracelio part, typically containing from about 8 to 50 carbon atoms, and in particular from 10 to 30 carbon atoms. The hydrophobic part may be either linear or branched and is often saturated, however, may be unsaturated, and optionally fluorinated. The hydrophobic part may contain a mixture of compounds with chains of different lengths, for example, obtained from fat, lard, palm oil, oil of seeds of sunflower or soybean oil. Such nonionic surfactants can be obtained from polyhydroxylated compounds, such as glycerol or sorbitol or other alditol. Examples of emulsifiers include ceteareth-10 to -25, ceteth-10-25, steareth-10-25 (i.e. C16-C18alcohols, ethoxylated 10-25 residues of ethylene oxide) and PEG-15-25 stearate or distearate. Other suitable examples include10-C20mono, di, or triglycerides of fatty acids. Additional examples include ethers, fatty18-C22alcohols and oxides (the t 8 to 12 EO).
Examples of emulsifiers which usually have a low HLB value, often a value from 2 to 6, are mono-or perhaps diesters of fatty acids and polyhydric alcohols, such as glycerin, sorbitol, aritra or trimethylolpropane. Fatty acyl part often is14to C22and in many cases is intense, including Cecil, stearyl, Arachidyl and behenyl. Examples include monoglycerides of palmitic or stearic acid, mono or desorbitada esters of myristic, palmitic or stearic acid, and trimethylolpropane monetary stearic acid.
A particularly desirable class of emulsifiers includes copolymers of dimeticone, namely dimethylpolysiloxane modified with polyoxyalkylene. Polyoxyalkylene group often represents a polyoxyethylene (POE), or polyoxypropylene (POP), or a copolymer of POE and POP. These copolymers often end With1-C12alkyl groups.
Suitable emulsifiers and co-emulsifiers are widely available under many trade names and designations, including the Abil™, Arlacel™, Brij™, Cremophor™, Dehydrol™, Dehymuls™, Emerest™, Lameform™, Pluronic™, Prisorine™, Quest PGPH™, Span™Tween™, SF1228, DC3225C and Q2-5200.
Cosmetically active substance
Used here cosmetically active substances can with erati substances with antiperspirant or deodorant active or dyes.
Substances with antiperspirant activity
This composition preferably contains a substance with antiperspirant activity. Substances with antiperspirant activity is preferably included in an amount of from 0.5 to 60%, in particular from 5 to 30% or 40%, and, particularly, from 5 or 10% up to 30 or 35% by weight of the composition.
Substances with the antiperspirant active for use here, often selected from salts with astringent action, including, in particular, salts of aluminium, zirconium and mixed aluminium/zirconium salts, including both inorganic salts, and salts with organic anions and complexes. Preferred binders salts include salts of aluminum, zirconium, and aluminum/zirconium halides and halogenerator salts such as chlorhidrate and activated alamoflorida.
Allogenicity usually defined by the General formula Al2(OH)xQy·wH2O, where Q is chlorine, bromine or iodine, x varies from 2 to 5 and x + y = 6, whereas wH2O represents a different degree of hydration. Especially effective halogenerator aluminium salts, known as activated alamoflorida described in EP-A-6739 (Unilever NV et al.), the contents of the description of which is incorporated herein by reference. Some activated salt does not retain its increased activity in PR is the absence of water, but used essentially in the anhydrous compositions, i.e. compositions that do not contain a distinct aqueous phase.
Zirconium active substances can usually be represented by the General empirical formula: ZrO(OH)2n-nzBz·wH2O, where z varies from 0.9 to 2.0 so that the value 2n-nz is zero or positive, n is the valency of B, and B is selected from the group consisting of chloride, other halide, sulpham, sulfate and mixtures thereof. Possible hydration to varying degrees presents wH2O. is Preferred that B is chloride and the variable z is in the range from 1.5 to 1.87. In practice, such zirconium salts themselves are usually not used only as a component of the combined aluminum and based on zirconium antiperspirants.
The above-mentioned aluminum and zirconium salts can be coordinated and/or bound water in various quantities and/or may be in the form of varieties of polymers, mixtures or complexes. In particular, hydroxyl salts of zirconium often present a number of salts having different numbers of hydroxyl groups. Particularly preferred may be the hydrochloride of zirconium aluminum.
Can be used antiperspirant complexes, based on the above-mentioned binders salts of aluminum is/or zirconium. The complex is often used in connection with the carboxylate group, and, mainly, this amino acid. Examples of suitable amino acids include dl-tryptophan, dl-β-phenylalanine, dl-valine, dl-methionine and β-alanine, and preferably glycine which has the formula CH2(NH2)COOH.
It is highly desirable to use a combination of halogenerator aluminum and clorhidrato zirconium together with amino acids such as glycine, which are disclosed in US-A-3792068 (Luedders et al.). Some of these Al/Zr complexes in the literature is usually called ZAG. ZAG active substance mainly containing aluminum, zirconium and chloride with Al/Zr ratio in the range of 2 to 10, mainly from 2 to 6, Al/Cl ratio from 2.1 to 0.9, and changing the number of glycine. The active substance of this preferred type, available from Westwood, from the Summit and from Reheis.
Other active substances which may be used include binders titanium salt, such as described in GB 2299506A.
Part of the solid salts in suspension antiperspirant composition usually contains a lot of any quantity of hydration water and any complexing agent, which may also be present in the solid active substance. However, when the active salt is included in the solution in a hydrophilic solvent, such as glycol, her weight is typically drop the et presence of any quantity of water.
If the composition is in the form of an emulsion, the active antiperspirant substance with properties will be dissolved in the dispersed phase. In this case, the active antiperspirant substance with properties often will be given from 3 to 60% by weight of the dispersed phase, in particular from 10% or 20%, up to 55% or 60% of this phase. Alternatively, the composition may take the form of a suspension, in which the active ingredient is an antiperspirant in the form of particles suspended in a water-immiscible liquid carrier. This song probably will not have any separate aqueous phase and can be appropriately called "essentially anhydrous", although it should be clear that a certain amount of water may be present in the associated with the active substance-antiperspirant or in a small amount in the form of a solution in a water-immiscible liquid phase. In such compositions, the particle size of the salt-antiperspirant often falls in the range from 0.1 to 200 microns with the average particle size is often from 3 to 20 μm. Can also be considered as a larger average particle size, or smaller, such as from 20 to 50 μm, or from 0.1 to 3 μm.
Active substances, deodorizing actions
Suitable substances with deodorizing activity may contain an effective deodorizing concentration of metal salts with antiperspirant the action, deodorizing fragrances, and/or antimicrobial agents, including, in particular, microbicides, such as chlorinated aromatic compounds, including derivatives of biguanide, materials which are known as Igasan DP300™ (triclosan), Tricloban™ and Chlorhexidine warranting special mention. Another class includes salts biguanide, such as salt, available under the trademark Cosmosil™. Substances deodorizing steps are typically used in concentrations from 0.1 to 25% by mass.
Other optional components include washed off the agents commonly present in an amount up to 10% mass/mass, to participate in the removal of the composition from the skin or clothing. Such wash off agents are typically non-ionic surfactants such as esters or ethers containing from8-C22alkyl part and a hydrophilic part, which may contain polyoxyalkylene group (POE or POP) and/or polyol.
Additional optional components present in this formulation contains one or more additional structural substances that may be used in addition to DOPA derivative. Here DOPAD can be a major structuring substance, this would imply the use of concentration, which is higher than the concentration is of additional structuring agents. However, in some preferred embodiments, the implementation of additional structural material may be present in an amount at least equal to the number DOPAD. In such preferred embodiments, the implementation of the DOPAD acts to weaken the properties of a secondary structure of the substance, so that the properties, when using the combined system structuring substances were better in at least one desired ratio compared with only additional structuring agents. The number of such additional structuring agents in the composition often varies from zero to not more than 15% of the composition. In some cases, additional structuring substance is present in a mass ratio to the DOPAD from 10:1 to 1:10.
Additional structuring agents used herein may be non-polymeric or polymeric. Can be included solid linear fatty alcohol and/or wax, but this is not preferred. In the anhydrous compositions, especially antiperspirants, which are suspension "pencils", polimernye additional structuring substance, sometimes called geleobrazovanie may be selected from fatty acids or their salts such as stearic acid or sodium stearate or 12 hydroc Starikova acid. In water "pencils" preferably do not use linear fatty acids, for example in water emulsion "pencils"because they can form insoluble precipitates with aluminium ions. Other suitable geleobrazovanie may contain dibenzylidene alidity, such as dibenzylidene. Following suitable geleobrazovanie can contain selected derivatives of N-acylaminoalkyl, including ester and amide derivatives, such as dibutylamine N-lauroylsarcosinate acid, such geleobrazovanie can be read in conjunction with 12-hydroxystearate acid or its ester or amide derivative. Even some of geleobrazovanie include amide derivatives of two or trekhosnovnykh carboxylic acids, such as alkyl N,N'-dialkylacrylamide, for example dodecyl N,N'-dibutylamine. Using the secondary structure of substances containing derivatives of N-acylaminoalkyl, in some particularly desirable compositions of their mass ratio to DOPAD selected in the range from 1:1 to 6:1.
Polymeric structuring agents, which can be used may contain organopolysiloxane elastomers such as the products of interaction of the polysiloxane with terminal vinyl groups with a cross-linking agent, or poly (methylsiloxane) or poly(a Hairdryer is zameshannyh) siloxanes with terminal alkyl or alkylpolyoxyethylene groups. A series of polyamides has also been described as structuring agents for hydrophobic liquids. Polymers containing siloxanes and groups, hydrogen bonding, which could be used as the secondary structure of substances, have been disclosed in WO 97/36572 and WO 99/06473. If there is a water dispersed phase, for structuring or thickening of this aqueous phase can be used polyacrylamides, polyacrylates or oxides polyalkylene.
It was also found that the compositions according to the invention may include dibenzylidene aldith, such as dibenzylidene sorbitol as an additional structuring substances, possibly together with the derived N-acylaminoacyl. It is desirable that the proportion of Aldata in the composition was chosen in the range from 0.1 to 0.5% by weight. In such compositions the mass ratio DOPAD to altitu, such as dibenzylidene the sorbitol, often chosen in the range from 3:1 to 10:1. When also using the derived N-acylaminoalkyl, as, for example, GP-1, then the mass ratio DOPAD to altitu often chosen in the range from about 4:1 to 10:1 and the mass ratio of GP-1, or other derived amino acids to DOPAD usually chosen in the range from about 5:2 to 2:3.
It is highly desirable that any additional structuring substance used here, it was fiber-forming, that is, education is Ivalo fibrous structure in a hydrophobic phase. Most preferably, the fiber-forming structure forming substance is a structuring agent, a fibrous structure which is not visible to the human eye.
Here, the composition can include one or more cosmetic additives, traditionally assumed for cosmetic hard or soft solids. Such cosmetic additives can include agents that enhance the sensation of the skin, such as talc or finely divided polyethylene, for example in amounts of up to about 10%; useful for skin substances such as allantoin or lipids, for example in an amount up to 5%; coloring agents; agents, cooling the skin, in addition to those already mentioned alcohols such as menthol, menthol and derivatives, often in an amount up to 2%, all the percentages are given by weight of the composition. Commonly used additives are odorants that are normally present in a concentration of from 0 to 4% and in many formulations from 0.25 to 2% by weight of the composition.
"Pencils", manufactured using DOPAD structuring substances can be either opaque or translucent, or even transparent, based at least in part, on the extent to which the matched refractive indices (RI) of the respective components. In respect of the compositions according to the present invention may receive is of translucent or transparent composition, because DOPAD structuring substance forms a fibrous structure in a hydrophobic liquid carrier, which is invisible to the human eye. Under the "selected" here means that the difference between the refractive index is less than 0.005 and preferably less than 0,002. In suspension "pencils" to achieve at least translucency, it is necessary to choose RI suspended cosmetically active substances, such as individual antiperspirant salts, RI suspendida mix oil carrier. This may facilitate the choice of suitable oils and, in particular, mixtures thereof, with RI above 1,46, for example, from a 1.46 to 1.56. With regard to suspended particles, the selection of RI can contribute to two factors. One involves crushing or grinding particles so as to greatly reduce or, ideally, remove the hollow spherical shell, which have different RI, and the second includes the regulation of the particle size in the production process or in the subsequent allocation process to obtain the distribution of particle size so that a small part is from 1 to 10 μm. The selection can additionally contribute to the change in RI suspended cosmetically active substances, such as aluminum containing substances with antiperspirant activity by after the respective processing water (rehydration) or by maintaining a relatively high water content during the production process. In the emulsion compositions of the respective components for the selection of the RI include the dispersed and the continuous liquid phase.
It is highly desirable to use a selection of RI, as described above, with the exception, to the extent necessary, additional suspended substances having a refractive index different from suspendida environment, such as, for example, suspended filler or additional cosmetically active substance, so that the resulting composition could miss at least 1% of the light (in the test described hereinafter).
Mechanical properties and packaging products
The compositions of this invention are structured liquids and dense. The composition of this invention typically will be sold as a product that contains a container with a large number of compositions, where the container has an opening for delivery of the composition and means for pushing the composition in the container toward the opening for delivery. Conventional containers take the form of a cylinder, oval in cross-section, with an opening for delivery at one end of the cylinder.
The composition of this invention can be sufficiently hard so that it is obvious not to be deformed when pressed by the hand and be suitable for use in the form and the Delia "pencil", in which a large number of compositions in the form of a rod placed in a cylindrical container having an open edge, which is the outermost part of the core composition is opened for use. The opposite edge of the cylinder is often closed.
Typically, the container will include a cover for the open edge of the container and an integral part of which is sometimes called a lift or piston fitted within the cylinder and capable of movement along its axis. The core composition is placed in the cylinder between the piston and the open edge of the cylinder. The piston is used to push the rod of the composition along the cylinder. The piston and rod compositions can be moved along the axis along the cylinder by physically pressing on the lower part of the piston with your finger or a rod inserted into the cylinder. Another possibility is that the rod attached to the piston protrudes through an opening or openings in the cylinder and is used for movement of the piston and rod. Preferably, the container also includes a transport mechanism for movement of the piston containing the rod with thread, which is along the axis of the rod through the hole, with a corresponding thread in the piston, and a device, installed in the cylinder for rotation of the rod. It is convenient to rotate the rod by hand wheel mounted on the closed end of the cylinder ie on the opposite side of the feed opening.
Component parts of such containers are often made of thermoplastic materials such as polypropylene or polyethylene. Descriptions of suitable containers, some of which have additional features that are found in the U.S. patents 4865231, 5000356 and 5573341.
Preparation of a composition
The compositions of this invention can be made by way of traditional manufacturing cosmetic solids. Such methods include preparation of a heated mixture of the composition at a temperature which is sufficiently increased in order to dissolve all structuring substance, filling the mixture into a form that may take the form of the distribution container, and then cooling the mixture, resulting in a structure of the substance is condensed in a network of fibers extending on water-immiscible liquid phase.
A suitable sequence of method for the composition, which is a suspension, includes first forming a solution structure of the substance in the water-immiscible liquid or in a water-immiscible liquids. This is typically done by shaking the mixture at a temperature high enough to dissolve all structuring agent (the temperature of dissolution), nab the emer temperature in the range from 50 to 140° C. the granular component, such as granular active ingredient is an antiperspirant, mixed with hot mixture. This should be done slowly, or granular solid material must be preheated in order to avoid premature gelation. The resulting mixture is then injected into the distribution container, such as a cylinder for "pencil". This is usually carried out at a temperature which is from 5 to 30°C higher than the temperature of curing of the composition. The container and contents are then cooled to ambient temperature. Cooling can be done, only leaving the container and its contents to cool. Cooling may be facilitated by blowing ambient or even chilled air above the containers and their contents.
In a suitable method for the manufacture of emulsion formulations, solution structure of the substance in the water-immiscible liquid phase is prepared at elevated temperature, as for suspension "pencils". When using any emulsifier, it is appropriately mixed with the liquid phase. Separately preparing an aqueous or hydrophilic dispersed phase by introducing the active substance in liquid antiperspirant part of this phase (if necessary: substances with antiperspirant activity can sometimes be supplied in aqueous solution, the which can be used as is). If possible, this solution of the active substance-antiperspirant, which will become the dispersed phase, preferably heated to a temperature similar to the temperature of the continuous phase with structuring substance, but without exceeding the boiling point of the solution, and then mixed with the continuous phase. Alternatively, this solution is injected at a rate which maintains the temperature of the mixture. If you want to work at temperatures above the boiling point of the dispersed phase, or at the temperature when the evaporation of this phase is significant, you can use a sealed device that allows you to reach a higher temperature. With structuring substances according to this invention is usually unnecessary. After mixing the two phases, the resulting mixture is filled distribution containers, usually at a temperature which is from 5 to 30°C higher than the temperature of curing of the composition, and allowed to cool as described above for suspension "pencils".
Many cosmetic compositions in accordance with the present invention, a mixture of a hydrophobic liquid carrier. In some convenient ways of cooking it is desirable to dissolve DOPAD structuring substance in the liquid component of the composition, such as alcohol, for example an alcohol carrier fluid, i.e. a branched aliphatic alcohol,for example isostearoyl alcohol or octyldodecanol, optional together with alcohol, has some Miscibility with water and a boiling point higher than the temperature of dissolution DOPAD in alcoholic liquid. This allows the remainder of the liquid-storage does not reach the temperature at which DOPA is dissolved or melted. The share of liquid carriers for dissolution DOPA often ranges from 15 to 65% by weight of the liquid carrier and, in particular, from 20 to 40%.
The preparation of the structure of matter
Derivatives of DOPA, used here as a structuring substances, can be obtained by the esterification of DOPA in the form of an acid with an alcohol corresponding to the radical, desired in DOPA derived.
In one suitable preceding stage DOPA acid (DOPAA) can be obtained by cyclization of aspartame, preferably in the presence of a large excess of an aliphatic alcohol with a low molecular weight, such as isopropanol, boiling under reflux for a long period. Preferably, the alcohol used in mass with respect to aspartame more than 50:1, for example, up to 100:1, and the reaction to continue for at least 10 hours at a temperature of phlegmy, for example from 15 to 24 hours. During the reaction aspartame is gradually dissolved. While cooling the resulting solution gives a white powder. Removing the solvent from the filtrate gives a firm the substance, after washing which acetone receive an additional amount of white matter, which is confirmed by the combined output DOPA acid 79%.
DOPAA can interact with the corresponding alcohol of formula RAOH, preferably in a molar ratio to the DOPAA at least from 1:1 to 10:1, especially from 1.5:1 to 7:1, and in particular at least 2:1 in dimethyl sulfoxide, in a suitable ratio of at least 4:1 (about:mass), preferably from 6:1 to 12:1, and preferably in the presence of an activator, such as carbonyldiimidazole, in the amount of, preferably, from 0.5 to 2 moles of activator per mole DOPA acid. The reaction is conveniently carried out at moderately elevated temperatures, for example up to 60°C, and, in particular, from 40 to 60°C for a period of at least 6 hours and preferably from 9 to 24 hours. The resulting solution is cooled rapidly by excess water in ambient temperature or colder, it is desirable that then the solution was cooled to ambient temperature, the solid precipitates and is filtered off, washed with water up until there remains no residual diimidazole, and then it can be cleaned by washing with diethyl ether or toluene and dried.
Example 1 and Comparative examples from CA on CI
Preparation of structural substances>
These examples and comparisons were performed following the conventional method using (2S-CIS)-(-)-5-benzyl-3,6-dioxo-2-piperazine acetic acid (DOPAA), which reacts with alcohols, and quantities of reagents and activators are described in Table 1 below.
In a 3-necked round bottom flask of 250 ml, equipped with a stirrer, were placed (2S-CIS)-(-)-5-benzyl-3,6-dioxo-2-piperazine acetic acid (DOPAA), and then stirring was introduced methylsulfoxide (8 ml per 1 g DOPAA) when the ambient temperature of the laboratory (about 22°C). DOPAA dissolved only partially. Then under stirring was added 1,1'-carbonyldiimidazole, in the amount indicated in the Table. Was an intensive foaming, and the reaction mixture was allowed to mix at room temperature for 45 minutes, after which the reaction mixture became transparent. Some alcohol was mixed with a transparent reaction mixture and kept at 50°C overnight (16 to 20 hours), and then left to cool to ambient temperature (about 22°C) and poured into water, getting a precipitate, which was filtered and washed with additional quantities of water to remove any residue diimidazole (which showed using1H NMR). The washed precipitate is then washed with diethyl ether, with the exception of NE, which was washed for that is the wall. The washed product was dried in a vacuum drying Cabinet to constant weight and were determined by its melting point, the results presented here were obtained using differential scanning calorimetry (DSC) with a heating rate of 10°C/min, except for those results that are tagged withET, which were obtained using a digital apparatus for measuring the melting point Electrothermal 9109. The purity of certain products could be determined using the selected method HPLC, since such derivatives were neliruum.
DOPAD substances in the Examples 1.16-1.18 received on a smaller scale using a modified method of reaction in which DOPAA activated with CDI in a single reaction vessel in 125 ml DMSO. After activation of the transferred volume in the reaction tube in Both'™ 12 local reaction centrifuge containing a corresponding number of selected alcohol.
Purity DOPAD substances PR-PR and CA-CK were determined using HPLC with reversed phase with ultraviolet (UV) detection.
Mobile phase was prepared, including 300 ml aliquots of deionized water to which was added 700 ml aliquots of acetonitrile purity HPLC and 1.0 ml triperoxonane acid (Aldrich spectrophotometric purity, TFA) and thoroughly mixed. 0.001 g sample CDP weighed in HPLC vial volume of the IOM 2 ml and brought up to volume with mobile phase.
Then the sample was analyzed on a HPLC analyzer, Hewlett Packard, equipped with a Hypersil ODS 5 μm C18, 250 x 4.6 mm @ Room Temp column, Hewlett-Packard 1050 Series Autosampler and a Hewlett-Packard 1050 UV Diode Array ® 210 nm Detector. The analysis was performed under the following conditions
Flow rate: 1.2 ml/min
Run time: 5 minutes
Injection volume: 20 ál
|An example or comparison||Alcohol||CDI||DOPA||Output||Purity||TPL|
|1.4||3,5-dime the Il-cyclohexanol||92||22||18,4||1,5||21||94||212|
|1.9||4-t-butylphenol||for 95.3||22,9||19,1||7,13||94,6||of 99.1||237|
|1.11||4-isopropylphenol||to 66.3||26,5||22,9||7,31||is 83.8||99,4||>230|
|1.12||3,5-dimethyle the ol||to 66.3||26,5||22,9||6,95||83,7||99,6||>200|
|1.15||Carvacrol||for 95.3||22,9||19,1||6,62||87,9||of 99.1||229ET|
|1.18||2-isopropoxyphenol||19, 0||4,6||the 3.8||0,57||of 37.8||98,8||178ET|
|CH||The cyclohexanol||of 147.4||35,4||30,5||2,12||20,4||91,4||224|
|CK||Benzyl alcohol :||for 95.2||22,8||19,1||5,8||87||99,7||222ET|
The materials used in the study gel or for the preparation of cosmetic compositions, their brand, in addition to the products of Example 1, were as follows:
1) Isostearoyl alcohol (ISA)(Pricerine 3515™ - Uniqema)
2) C12-15alkylbenzoic (Finsolv TN™ from Finetex Inc.)
3) Octyldodecanol (Eutanol GTM- Cognis)
4) volatile cyclomethicone (DC 245™ - Dow Corning Inc.)
5) Hydrogenated polydecene (Silkflo 364 NF™ - Albemarle)
6) 1,1,5,5-tetraphenylsilane (DC704™: Dow Corning Inc.)
7) Di-n-butylamide N-lauroyl-L-glutamic acid (GP-1™-Ajinomoto Co Inc)
8) Copolyol dimetikona: (Abil EM90™ -Th. Goldschmidt AG)
9) Al/Zr tetrachlorohydrex glycine complex (Reach 908™ -Reheis Inc.)
10) Crushed macrosporiosis AACH (A418™ Summit)
11) 50% aqueous solution of Al/Zr pentachloride (Zirconal 50™ BK Giulini)
12) Modified water AZG, made yourself freeze-drying of a solution AZAG (Rezal 67™) and filtration with obtaining bulk solids without hollow particles (˜37% of particles <10 μm) and treated with water to RI =1,526.
13) PG5 - Al/Zr pentachloride glycine complex (BK Giulini) without hollow particles (˜25% of particles <10 μm) (RI = 1,530)
14) BMA - Benzyl alcohol - Acros
15) DBS - Dibenzylidene sorbitol (Roquette Corp)
16) 12-HSA - 12-hydroxystearate acid (CasChem Inc.)
17) Rezal 36 GP (solid Al/Zr tetrahydrochloride glycine salt from Reheis Inc.)
18) Reach 908 (solid Al/Zr tetrahydrochloride glycine salt from Reheis Inc.)
19) Versamid 930 - polyamide from Cognis
20) DDK H18, silica from Wacker-Chemie GmbH
21) HDD H30, silica from Wacker-Chemie GmbH
22) HDD H30RX, silica from Wacker-Chemie GmbH
23) three(1,2-propandiol) n-butyl ether (Dowanol TPnB™ from Dow Corning Inc.)
24) propane-1,2-diol from Fisher
25) di(propane-1,2-diol) from Acros
26) PEG-30 dipolyhydroxystearate (Arlacel P135™ from Uniqema)
Example 2 - Structured gels
In this example, the gels prepared or tried to prijaviti in the range of typical organic solvents having a refractive index, shown in Table 2 below, using the structures of the compounds obtained in Example 1 or comparison.
Gels were prepared in a transparent glass flasks with a volume of 30 ml. of Solvent and gelling agent in visuali directly into the flask to obtain the total mass of the mixture 10, Into the flask were placed a little Teflon stirrer, and the mixture was stirred and heated until dissolution of cyclopeptide. Then the flask was removed from heat and the solution was allowed to cool and thicken in a fixed position.
The hardness of the gel was determined with the help of an experienced expert on the gels, using the qualitative assessment, by comparing with a standard gel after storage of the gel at ambient temperature for 1 day or 3 days. Transparency was determined by visual assessment, comparing with the standards, and for some of the samples were measured light transmission using the conventional method described in WO 00/61082 included here as a reference. The results are summarized here in Table 4.
The stability of the gel was evaluated in a series of samples with structural substance in a concentration of 1.5% by weight, by storing them for a long period of time at ambient temperature (20 to 25°C) and observing the change, if it occurs in their appearance or properties after a set period of time, this time a month. The results are summarized in Table 5.
|50:50 ISA: DC245||1,4278|
|50:50 ISA: Finsolv TN||1,4700|
|50:50 ISA: Silkflo 364NF||1,4552|
|Transparency||The hardness of a gel||Description|
|3||Average||L||There are liquid|
|4||Medium/Firm||D||Did not dissolve|
|50:50 ISA:Finsolv TN||1,5||T*93,3,G||1,5||T,3,G||1,5||T*83,5,G|
|50:50 ISA:Silkflo 364NF||1,5||t,4,G||1,5||T,3,G||1,5||T*81,5,G|
|50:50 ISA: DC245||1,5||t, 1, G+U||1,5||T,3,G+U||1,5||T,r,G+U|
|50:50 ISA:Finsolv TN||1,5||t, 1, G+U||1,5||T*84,3,G||1,5||T,r,G+U|
|50:50 ISA:Silkflo 364NF||1,5||t, 1, G+U||1,5||T,3,G||1,5||T,r,G+U|
|50:50 ISA: DC245||1,5||t,2,G+U||1,5||O,3, G||1,5||U+L|
|50:50 ISA:Finsolv TN||1,5||T*68,3,G||1,5||t/O,3,G||1,5||T,3,G|
|50:50 ISA:Silkflo 364NF||1,5||t,1,G||1,5||0,3,G||1,5||t,3,G|
|50:50 ISA:Finsolv TN||1,5||t,3,G|
|50:50 ISA:Finsolv TN||t,3,G|
|50:50 ISA:Finsolv TN||1,5||T,3,G|
|ISA||1,5||t,2,G||1,5||0,Or G||1,5||O P|
|50:50 ISA:Finsolv TN||1,5||t,1,G||1,5||T,1r,G||1,5||O P|
|50:50 ISA:Silkflo 364NF||1,5||t,2,G||1,5||T,1r,G||1,5||O P|
|ISA||1,5||U+L||1,5||O P||1,5||O P|
|50:50 ISA:DC245||1,5||U+L||1,5||U+S||1,5||O P|
|50:50 ISA:Finsolv TN||1,5||U+L||1,5||O P||1,5||O P|
|50:50 ISA:Silkflo 364NF||1,5||U+L||1,5||U+S||1,5||O P|
|ISA||1,5||L+O,P||1,5||O P||1,5||O P|
|50:50 ISA:DC704||1,5||O,0, g||1,5||O P||1,5||O P|
From the above it will be obvious that the comparison of geleobrazovanie, some of which were praised in the prior art, is clearly worse than geleobrazovanie used is presented in the present invention.
|Product||Description original gel||Description of gel after storage at room temperature|
|PR 1.1||Transparent, medium gels||Unchanged after 12 months|
|PR 1.2||Transparent, solid gels||Unchanged after 12 months|
|PR 1.3||Transparent, soft gels + undissolved solids||Unchanged after 12 months|
|PR 1.4||Transparent, medium gels||Unchanged after 12 months|
|PR 1.5||Transparent, soft, koutsokoumnis gels + undissolved solids||DC245/Finsolv original mix started to become opaque and the percolation of the solvent through day 1, but does not deteriorate after 8 months|
|PR 1.6||Translucent, soft/medium gels||Unchanged after 12 months|
|PR 1.7||Transparent/opaque medium gels||Slight loss of transparency after 3 months, but no further changes over the next 9 months|
|PR 1.8||Transparent medium gels. No gel DC245 with whom ESU||Unchanged after 8 months|
|PR 1.9||Transparent medium gels||Unchanged after 6 months|
|PR 1.10||Transparent/translucent middle gels||Unchanged after 6 months|
|PR 1.11||Transparent medium gel||Unchanged after 6 months|
|PR 1.12||Transparent solid gel||Unchanged after 6 months|
|PR 1.13||Translucent middle gels||Unchanged after 6 months|
|PR 1.14||Transparent medium/hard gels||Unchanged after 3 months|
|PR 1.15||Translucent middle gel||Unchanged after 3 months|
|PR 1.16||Translucent middle gel||Unchanged after 2 months (will be corrected)|
|PR 1.17||Transparent medium gel||Unchanged after 2 months (will be corrected)|
|PR 1.18||Transparent medium gel||Unchanged after 1 month (will be corrected)|
|PR 1.19||Transparent medium or medium firm gel||Unchanged for less is th least 7 months|
|CA||Transparent/translucent, soft/medium gels||The gels were not suitable for the manufacture of "pencils"because they became very soft and opaque in 2 weeks and leaking within 4 to 6 weeks|
|CB||Translucent, soft/medium gels||The gels were not suitable for the manufacture of "pencils"because they became very soft and opaque in 2 weeks and leaking within 4 to 6 weeks|
|CC||Translucent, soft, koutsokoumnis gels||The gels were not suitable for the manufacture of "pencils", as they became opaque and collapsed within 1 day|
|CD||Opaque paste or white sediment in a transparent solution||No gel|
|CE||No gel||No gel|
|CF||Has not been dissolved or precipitious in the form of an opaque crystalline viscous mass||No gel|
|CG||Opaque paste||No gel|
|CH||Translucent medium or medium/soft gel||The gel was opaque, often within days and was falling apart within 1 to 6 weeks|
|# example||Ave. 3.1||Ave. 3.2||Ave. 3.3||Ave. 3.4||Ave. 3.5|
|The product of Example 1.2||2,5||2,5||1,5||1|
|The product of Example 1.6||1,5|
|The amount of applied product (g) WetorDry at to||0,35||0,25||0,31||0,27||0,3|
|White BP.=24 h on WetorDry||13||16||14||27||20|
|The amount of applied product (g) to coat at to||0,99||0,63||0,82||0,63||1,08|
|White BP.=24 h on wool||17||17||16||15||20|
Comparative data for commercial suspension "pencils", structured using GP1 (GS), and commercial suspension "pencils", structured wax (WS), are given in Table 7.
|The amount of applied product (g) WetorDry at to||0,40||0,39|
|white BP.=24 h on WetorDry||28||121|
|The amount of applied product (g) to coat at to||0,61||1,10|
|white BP.=24 h on wool||23||110|
From Table 7 we see that the "pencils" of suitable strength can be obtained using the structure of the substances according to this invention at relatively low concentrations structuring agents. Moreover, even if the suspension "pencils", structured using the structure of the substances according to this invention, a bit softer (as measured by penetrometer)than GS or WS "pencils", and therefore could be expected to have higher pay-off" (the number of the applied product and more visible raids, "pay-off" similar to GS and WS "pencils"and white on the contrary lower.
Example 4 - transparent suspension "pencils"
In this Example, "pencils" was prepared using the method of Example 3 together with the stage of preparation. At the stage of preparation of the first measured RI substances the antiperspirant activity, using the standard method (Becke line test). Then determined the proportion of each of the oils carrier (counting and measuring), so that their average mass refractive index closely correspond to RI substances with antiperspirant activity. These compositions are summarized in Table 8.
|ISA||MT 18 : 34||17,61||17,36||17,55||17,61||17,36||16,71||17,49|
|Transparency (%P)||44||a 12.7||15,4||to 12.0||9,9||1,6%||0,7||5,9|
|The amount of applied product (g) to coat at to||nd||0,88||0,54||0,92||0,58||n/d||0,83||0,97|
|white BP.=24 h on wool||nd||15||17||20||17||n/d||17||13|
|"nd" means that the property was not defined|
|Benzyl alcohol :||8,81||19,68||1,96|
|Finsolv TN||12,21||to 22.83|
|Transparency (Visual scale)||n/d||n/d||2||3||0||-9|
|"nd" OSN which includes, that property was not specified|
|Benzyl alcohol :||1,92||1,98|
|; The ü (Visual scale)||7||6||4||1||0|
|"nd" means that the property was not defined|
From Table 8 we can see that has received relatively soft pencil, using an extremely low concentration of structural substances of the present invention, and the pencil has excellent transparency. "Pencils", containing GP-1 as a co-structure of matter, were more solid and still retain acceptable transparency. "Pencils" with similar hardness were obtained by the inclusion of dibenzylidene sorbitol.
Example 5 - opaque emulsion "pencils"
At the first stage of manufacture of opaque emulsion "pencils" of the present invention, a solution of the selected structure of the substances according to the invention, and, if present, GP1, ISA was prepared in the same manner as in the method for manufacturing the suspension "pencils" (Example 3). The remaining water-immiscible oil-carriers together with an emulsifier, Abil EM 90, was heated to 85°C on an oil bath at a speed of mixing with the shift of 2500 Rev/min. a Solution of the active substance-antiperspirant was heated up to 80°C and slowly added to a mixture of the oil/emulsifier, and the temperature obtained inthe mixture was maintained constant by heating at 85° C and subjected to shear efforts at 7500 rpm for 5 minutes. The emulsion was mixed into the solution structure of matter, which allowed to cool to ˜90°C. the resulting mixture was gently stirred to achieve complete mixing, poured in commercial 50 g cylinders for "pencils" at about 80°C and allowed to cool.
Data structures and properties "pencils" are summarized in Table 9.
|The product of Example 1.1||1,5|
|The product of Example 1.2||1,5|
|The amount of applied product (g) to coat at to||0,66||0,80|
|white BP.=24 h on wool||17||18|
Table 9 shows that even if the pencil in Example 5.1 was relatively mild for "pencil", he had a reasonable "pay-off" and only invisible plaque. Visually, it was slightly translucent. Harder pencil Example 5.2 also gave acceptable "pay-off" and invisible attacks.
Example 6 - transparent emulsion pencil
This example was repeated a common method of making emulsion "pencils", described in Example 5, starting from the preparation phase for the selection of the refractive index to obtain a translucent emulsion "pencil".
At the stage of preparation were obtained or measured refractive indices of the components of organic and aqueous phase in the emulsion, and determined the proportions of these components on the basis of counting or measurement, so that two phases are approximately fitted the refractive indices. Prepared two phases containing the established proportions of the components, we measured their refractive indices, and the proportions of oil-carriers in the continuous (water-immiscible) phase brought up to value required to more closely match the RI of the dispersed aqueous phase.
When using polymer Versamid, it was dissolved simultaneously with DOPAD. The suspension consisted of any number of silicon dioxide in fracc the Y. water-immiscible oil(ate) and any active ingredient is an antiperspirant, supplied in the form of solids, first dissolved in a given quantity of water.
In the Examples 6.10 and 6.11, the fraction ISA (7.4 parts for 6.10 and 5.9 parts for 6.11), the entire DC245 and Arlacel P135™ United in a beaker and heated to about 40°C to dissolve Arlacel. Pre-prepared aqueous solution Reach 908 then poured into a solution of Arlacel P135 under stirring verkhnepashino stirrer. The speed of the mixing apparatus was increased to 1500 rpm for two minutes to form an emulsion, and then the aqueous solution forms the dispersed phase. The emulsion was closed and heated to 55-58°C. DOPAD and the remaining ISA combined in a beaker together with propane-1,2-diola, di-(propane-1,2-diola), Dowanol TPnB™ and Finsolv TN™ (atmosphere) and heated to 135-140°C on a hot plate with stirring until dissolution DOPAD. The hot plate was then removed and the solution was allowed to cool to 65-70°C without stirring. The resulting solution is then poured into the emulsion and the mixture was slightly stirred to ensure complete mixing. The mixture is then poured into the cylinders for "pencils" and cooled in ambient conditions. The composition and its properties are summarized in Table 10.
|Example||6.1td align="center" namest="c5" nameend="c6"> 6.2||6.3||6.4||6.5||6.6|
|Finsolv TN||5,71||by 8.22||of 5.05||the 5.65|
|Benzyl alcohol :||br4.61|
|Hardness (mm)||18,6||n/d||the 13.4||11,9||17,2||14.4V|
|Transparency (Visual scale)||1||n/d||n/d||n/d||n/d||4|
|The amount of applied product (g) to coat at t||1,39||n/d||n/d||n/d||n/d||n/d|
|Hardness (mm)||to 19.9||17,2||14,8||14,7||17,6||17,1|
|Transparency (Visual scale)||-1||7||n/d||n/d||n/d||n/d|
|"nd" means that the property has not been defined is Elena|
Description "pencil" - defining properties
(i) Hardness "pencil" - penetrometer
The hardness and stiffness of the composition, representing a solid substance can be determined using penetrometry. If the composition is a softer solid, it will be observed as essentially devoid of any stability in the study on the penetrometer. A suitable method is the use of the laboratory setup of PNT penetrometer equipped with a wax needle Seta (weighing 2.5 g), which has a specified cone angle at the tip of the needle 9°10' ± 15'. Use the sample composition with a flat upper surface. The needle is lowered to the surface of the composition, and then carry out the measurement of the penetration hardness, by the fall of the needle and needle holder under a total weight (i.e. the combined weight of the needle and needle holder) 50 g for a period of 5 seconds, and then mark the depth of penetration. It is desirable to carry out tests on a number of points of each sample and the results averaged. Using a test of this type, suitable hardness for use in the distribution container with an open edge represents a penetration of less than 30 mm in this test, for example in the range of 2 to 30 mm, Preferably, the penetration is in the range from 5 mm to 20 mm
In the preliminary Protocol for this test measurements on the rod performed in the cylinder "pencil". The rod was twisted from the open edge of the cylinder, and then cut off, leaving a flat, uniform surface. The needle was carefully lowered to the surface of the rod, and then a measurement was performed penetration hardness. This process was carried out in six different points on the surface of the rod. Given the hardness readings represent the average of 6 measurements.
ii) Application of solid pencils (pay-off) (the number of the marked product)
Another property of the composition is the amount that is delivered to the surface when applied to the surface (representing the overlay product rod on human skin), sometimes called "pay-off". For this test application in the case, when the composition is a solid rod, capable of retaining its shape, the sample composition with a standardized shape and size and placed in the device, which causes the sample to the test surface in standardized conditions. The number transported to the surface, defined as the increase in the mass basis, to which is applied the composition. If you want, later you can define the color, opacity or transparency of the coating. In a separate methodology for such studies coatings and white, suitable for dense solid "pencils", use the unit DL the coating from the terminal on the basis of a standardized conditions, and then determined the average degree of the white coating using image analysis.
Used bases were:
a: 12 x 28 cm strip of grey abrasive paper (3M™ P800 WetorDry™ Carborundum paper)
b: 12 x 28 cm strip of black worsted wool fabric. Before using these principles were weighed. "Pencil" is not pre-used and a dome-shaped top surface is not changed.
The device contained flat base, to which by means of a clamp at each end was fastened a flat substrate. Hour, with a frame, which accommodates a standard size cylinder "pencil", was mounted on the arm, which is moved horizontally along the surface of the substrate by means of a pneumatic piston.
Prior to the measurement, each pencil was kept at the ambient temperature of the laboratory during the night. The rod is pushed to the edges of the cylinder were measured quantity. Then the cylinder was placed in the device and put the spring to position the pencil against the substrate with a standardized force. The device is operated so as to hold the rod horizontally through the base eight times. The Foundation was carefully removed from the device and again weighed. White coating may subsequently be determined as described in (v) below.
The white coating of the test (ii), above, were evaluated soon after application (i.e. within 30 minutes) or after approximately 24-hour interval.
This was done using a Sony XC77, monochrome video camera with Cosmicar lenses with a focal length of 16 mm, located vertically over the black table, to remove shadows lit high angle using fluorescent tubes. This device was first calibrated using a reference white card, then included fluorescent tube long enough to give a constant light output. The Carborundum cloth or paper with a coating on it from the previous test, was placed on the table and to record the image used on the camera. Chose the image area coverage and analyzed using an image analyzer Kontron IBAS™. The analyzer speculative shared the image on a large series of pixels, and to determine the level of gray of each pixel on a scale from 0 (black) to 255 (white). Calculated average intensity of gray. It was the determination of the whiteness of the coating, the higher the number, the whiter the floor. It was assumed that the low numbers show a clear coating that allows you to see the color of the canvas.
iv) the transparency of the part - transmission
The translucency of the composition can be defined by the m locations of the sample standardized thickness in the light beam of the spectrophotometer and measuring the transmittance, as a percentage of the missed light in the absence of a gel.
This test was performed using a dual beam spectrophotometer Perkin Elmer Lambda 40. Hot sample of the composition was poured in a cell volume of 4.5 ml, made of poly(methyl-methacrylate) (PMMA), and allowed to cool to ambient temperature 20-25°C. Such cuvette gives the thickness of the composition 1 see the Measurement was carried out at 580 nm with an identical but empty cuvette in the reference beam of the spectrophotometer, after keeping the sample in the cuvette within 24 hours. The transmittance was determined at any temperature in the range from 20-25°C, usually quite accurate, but if you need greater precision, the measurement is carried out at 22°C.
v) the transparency of the composition - scale visual assessment
The gel contained in a cell with a thickness of 1 cm, was placed directly on a sheet of white paper on which black printed 21 set of numbers. The size and thickness of figures systematically changed and were numbered from -12 (the large, thick set) 0 to 8 (the small, thin set). The score assigned to each gel, represented a set with the largest room, which can clearly be disassembled through the gel, the higher the number, the greater the transparency.
1. The antiperspirant composition containing
i) a substance with antiperspirant activity,
ii) a continuous phase containing nesmeshivayuscheysya water carrier liquid, and
iii) from about 0.15 to 20% by weight of the specified continuous phase structure of the substance, which contains cyclopeptide derived, further DOPAD, having the General formula
where RArepresents a saturated, unsaturated or aromatic carbocyclic group containing not more than 2 rings, 6-membered ring containing a methylene bridge, or 2,2,6,6-tetramethyl-4-piperidinyl,
where RAnot necessarily may be substituted by at least one linear or branched C1-16the alkyl, C2-6alkenyl, ether or ester group;
provided that RAis not unsubstituted cyclohexyl.
2. The composition according to claim 1, where RAin DOPAD is substituted carbocyclic saturated, unsaturated non-aromatic or aromatic ring.
3. The composition according to claim 1 or 2, where RAin DOPAD represents a single ring.
4. The composition according to claim 3, where the ring RArepresents a substituted tsiklogeksilnogo group.
5. The composition according to claim 3, where the ring RArepresents cyclohexenyl group, optionally substituted.
6. The composition according to claim 3, where the ring RArepresents a phenyl group, optionally substituted, or naphthanilide group, optionally substituted.
7. Com is azizia according to claim 1, where RAsubstituted by at least one alkyl group.
8. The composition according to claim 7, where the alkyl group is a methyl or isopropyl.
9. The composition according to claim 7, where RAsubstituted alkyl groups of from two to four.
10. The composition according to claim 9, where at least one of the alkyl groups is a methyl or optionally isopropyl.
11. The composition according to claim 1, where RArepresents a cyclohexane or benzene ring substituted methyl and ISO-propyl group, who are paraprotein in relation to each other.
12. The composition according to claim 1, where RAsubstituted by hydroxyl, ether or ester Deputy.
13. The composition according to claim 1, where DOPAD represents the balance of piperidinol, replaced by stands.
14. The composition according to claim 1, where the radical RAndrepresents the balance of thymol, isopinocampheol and 3.5-dealkilirovanie.
15. The composition according to 14, in which 3,5-dealkilirovania represents 3,5-dimethylcyclohexane.
16. The composition according to claim 1, where the radical RArepresents the balance of thymol.
17. The composition according to claim 1, where the radical RArepresents the balance of carveol or carvacrol.
18. The composition according to claim 1, where DOPAD is present in a concentration of from 0.1 to 15% by weight of the composition.
19. The composition according to p where DOPAD present in concentration the AI from 0.5 to 3.5% by weight of the composition.
20. The composition according to p where DOPAD is present in a concentration of from 0.4 to 8% by weight of the continuous phase.
21. The composition according to p, where the radical RAin DOPAD represents the balance of thymol.
22. The composition according to claim 1 where the water-immiscible carrier liquid contains a silicone oil and/or asilicone hydrophobic organic liquid selected from hydrocarbons, hydrophobic aliphatic esters, aromatic esters, hydrophobic hydrophobic alcohols and ethers.
23. The composition according to claim 1 where the water-immiscible carrier liquid contains a silicone oil in an amount of at least 10% by weight of the entire composition.
24. The composition according to claim 1, containing not more than 3% by weight of any fatty alcohol that is solid at 20°C.
25. The composition according to claim 1 containing no more than 3% of any waxy substance, which is solid at 30°, softened and melted and dissolved in water-immiscible liquid at 95°C.
26. The composition according to claim 1, where DOPAD used in conjunction with additional structuring substance containing a derivative of N-acylaminoalkyl, and/or hydroxystearic acid, and/or dimensionally.
27. The composition according to p where additional structural substance is dibutylated N-lauroylsarcosinate acid.
28. Composition p is p, where additional structural substance use in mass with respect to DOPAD from 1:10 to 10:1.
29. The composition according to p where additional structuring substance contains dibutylated N-lauroylsarcosinate acid or 12-hydroxystearic acid in a mass ratio to the DOPAD from 1:1 to 6:1.
30. The composition according to clause 29, where additional structuring substance contains dibenzylidene in mass with respect to DOPAD from 1:3 to 1:10.
31. The composition according to claim 1, containing a suspension of cosmetically active substances in a structured hydrophilic liquid carrier.
32. The composition according to p, where the carrier fluid and suspended cosmetically active substance have comparable coefficients of refraction and transmittance is at least 1%.
33. The composition according to claim 1, which is the emulsion cosmetically active substances in solution in the hydrophilic, preferably miscible with water, the dispersed phase.
34. The composition according to p, where the dispersed phase contains a diol or polyol.
35. The composition according to p, where the dispersed phase contains glycerin or 1,2-propandiol.
36. The composition according to p containing from 0.1 to 10% by weight of nonionic emulsifier.
37. The composition according to p, where the emulsifier is copolyol of alkyldimethyl.
38. The composition according to p, where the refractive indices of the dispersed and n is discontinuous phase of the emulsion comparable.
39. The composition according to claim 1, placed as a rod in the distribution container, where the specified container has a hole for the feed rod and the means for loading the specified rod through the hole.
40. The composition according to § 39, where the core is a dense gel, such that the needle penetration test (CPT) with the angle of the cone 9° 10 min, included in the gel is not more than 30 mm, when falling under the total mass of 50 g for 5 sec.
41. A method of obtaining a composition according to claim 1, which includes stages:
A1) the introduction of water-immiscible carrier liquid structuring substance representing one or more of the substances specified in claim 1,
A2) mixing the liquid carrier with solid or dispersed in the liquid phase, comprising a cosmetically active substance in particulate or dissolved form, suspended in a water-immiscible liquid,
A3) heating a liquid medium or a mixture containing the medium to high temperature at which a structure of the substance is dissolved or dispersed in water-immiscible liquid carrier,
at this stage a1), A2) and A3) are performed in any order followed:
b1) introducing the mixture into a form, which, preferably, is a distribution container, and then
c1) cooling or camoufla the vision of the mixture to a temperature in which solidifies liquid media.
42. The method according to paragraph 41, where DOPAD structuring substance dissolved in a single component hydrophobic liquid carrier at a temperature higher than the temperature, which reached a balance of hydrophobic media.
43. The method according to paragraph 41, which includes a step of pouring the mixture at an elevated temperature distribution in the container, and cooling the mixture in obtaining the composition according to § 39.
44. Cosmetic method for preventing or reducing perspiration on human skin comprising the local application to the skin the composition according to any one of claims 1 to 40.
45. Derived cyclopeptide (DOPAD), characterized in claim 1, where RAndis 2,2,6,6-tetramethyl-4-piperidinyl.
46. The gel basis for the introduction of substances with antiperspirant active containing water-immiscible oil and cyclopeptide derived (DOPAD)described in claim 1, except for compounds in which RArepresents the balance of menthol in a concentration effective for thickening water-immiscible oil, optionally together with additional structuring substance.
19.12.2002 - claims 1 to 44;
18.01.2002 - PP and 46;
01.08.2002 - PP and 46.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to compositions and methods for treatment of depressive disorder in subject using the therapeutically effective dose of agonist(s) of delta-receptors of the general formula: wherein Ar1 represents a 6-membered carbocyclic aromatic ring with a substitute Y at its carbon atom wherein Y represents carboxamide of the formula: CONR9R10 wherein both R9 and R10 represent ethyl group; Z is chosen from group consisting of hydrogen atom (H), -OH and alkoxy-group; Ar2 represents a 6-membered carbocyclic aromatic ring with a substitute X at its carbon atom wherein X represents H, or pharmaceutically acceptable ester or salt of such compound. Invention provides antidepressant effect in a patient in using indicated compounds in lower doses as compared with the known agonists of delta-receptors showing the related chemical structure with compounds proposed.
EFFECT: improved method of treatment, enhanced and valuable medicinal properties of compounds.
17 cl, 1 tbl, 21 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to compounds of formula I , wherein G is carbon or nitrogen atom; A is i) phenyl substituted with any from -COOH, -CONH2, COOCH3, -CN, -NH2 or -COCH3; ii) naphthyl, benzophuranyl, and quinolinyl; and iii) formulae , , .
Compounds of present invention are useful in particular in pain treatment.
EFFECT: new agents for pain treatment.
FIELD: organic chemistry.
SUBSTANCE: claimed method includes reaction of C60-fullerene with 1,2-diaminepropane in presence of Cp2TiCl2 as catalyst in toluene medium at room temperature (approximately 20°C) for 44-52 hours. Yield of target product is 73-90 %. Compound of present invention is useful as chelating agent, sorbent, biologically active compound and for production of new materials with desired electronic, magnetic and optical properties. .
EFFECT: new compound; method of increased yield and selectivity.
1 tbl, 1 ex
FIELD: organic chemistry, medicine, ophthalmology, pharmacy.
SUBSTANCE: invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the general formula (I): wherein X1, X2, X3, X4 and X5 mean -CH2 or one of them represents -NH and another X1-X5 represent -CH2; k = 0, 1 or 2; when t = 2, then radicals R1 are similar or different; R1 represents direct or branched (C1-C8)-alkyl or (C1-C8)-alkoxy-group; A means phenyl or pyridinyl; R2 means hydrogen atom (H), hydroxyl, halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; n = 0, 1-4; radicals R2 are similar or different, when n > 1; p = 0 or 1-5; Y means -OC(O); Z means -CH, or to their pharmaceutically acceptable salts. Compounds of the formula (I) possess agonistic activity with respect to muscarinic receptors and can be used in medicine as medicinal preparations for treatment of neurodegenerative diseases or diseases associated with increased intraocular pressure.
EFFECT: valuable medicinal properties of derivatives.
6 cl, 1 tbl, 2 dwg, 16 ex
and the polymer containing lactide links, glycolide links and links tartaric acids - which are found in the polymer at the next sootnoshenii: lactide units constitute from about 71% to about 73%, glycolide links from about 26% to about 28%; and the parts of tartaric acid from about 1% to 3%, and the amino group of the compound (a) relate ionic bond with the carboxyl groups of the acid units of the polymer; the particles of compound I, an average size of from about 10 microns to about 100 microns; pharmaceutical composition with delayed release and two methods of treatment of various diseases, including the introduction to the patient an effective amount of compound A, or microparticles
SUBSTANCE: invention relates to cosmetology, namely, represents transparent cosmetic or dermatologic composition, containing, at least, one antiperspirant active substance and, at least mandelic acid and water.
EFFECT: ensuring absence of opacity transparence and minimal stickiness of cosmetic composition.
8 cl, 3 ex, 1 tbl
SUBSTANCE: invention can be used in paint and varnish, cosmetic and other industries. Offered aluminium pigments are at least partially covered with greasing and having a) water spread coefficient within 40000 and 130000 cm2/g; b) average thickness h within less than 100 to 30 nm calculated from water spread coefficient and integral distribution h50 by data processing on thickness of scanning electron microscopy; c) relative width Δh of thickness distributions determined by data processing on thickness of scanning electron microscopy and calculated by corresponding relative frequencies integral curve by formula: 70% to 140%; d) form-factors d50/h more than 200; e) roughness degree calculated by specific surface area measured by BET method and spread coefficient according to the following formula: BET value/2 spread coefficient, from 0.30 to 0.9. Method of production of these pigments, as well as varnishes containing these pigments is offered.
EFFECT: production of very thin aluminium pigments without adhesive polymer film having excellent spreading capacity, high gloss value and improved metallic appearance, as well as reduced agglomeration tendency.
26 cl, 10 ex, 4 tbl, 5 dwg
SUBSTANCE: invention refers to application of compounds of formula [V] used for coolness effect. In general formula [V] X is independently selected from nitro, halogen, and C1-6alkoxy where alkyl group is linear with direct or branched chain and is bonded through oxygen atom; and Y is independently selected from hydroxy and halogen-C1-6alkyl where alkyl group is linear with direct or branched chain and is substituted with at least one halogen atom; provided that Y represents hydroxy, X is not nitrogroup. Compounds can be used in compositions for tooth-paste, mouth wash and foodstuff rinsing.
EFFECT: production of tetrahydropyramidon derivatives used in compositions for tooth-paste, mouth wash and foodstuff rinsing.
19 cl, 4 ex
FIELD: medicine, stomatology.
SUBSTANCE: medicinal and preventive elixir for oral cavity care contains alcohol, surface-active substance, glycerin, perfume, biologically active additive with chloroform extract of herbs, i.e. nettle, plantain, myrrh, flowers of chamomile and calendula, Vitamin 'A', sodium fluoride, anion-active SAS, antiseptic, as preservative - nipagin, nipasol, perfume, colouring agent.
EFFECT: prolonged biological activity, anti-inflammatory capacity and expressed desensitising property.
2 cl, 4 ex
FIELD: medicine, cosmetology.
SUBSTANCE: invention consists in creating a preparation, containing efficient amount of superoxidedismutase.
EFFECT: invention allows strengthening nails, reducing their fragility, improving nail content, enhancing their elasticity, reducing nail splitting, as well as restoring healthy appearance of nails and accelerating their growth.
5 cl, 3 ex
SUBSTANCE: invention concerns dentistry, particularly compositions for oral cavity hygiene improvement. The group of inventions includes composition for oral cavity care of increased stability and dental deposit fighting effect, as well as method for improving composition stability, and method for obtaining water composition for oral cavity care. The claimed composition includes carrier acceptable for oral cavity and containing a combination of ferment, cetylpyridinium chloride and reducing agent.
EFFECT: obtaining a composition with improved hygienic properties and dental deposit fighting effect.
37 cl, 2 ex, 11 tbl
FIELD: medicine, cosmetology.
SUBSTANCE: invention relates to cosmetics. The invention is characterised by that harmful effect of depilation, for example, inflammation appeared during depilation of axillary space and antiperspiration can be reduced by a composition of antiperspirant containing natural oil and glycerin in total concentration from 1.5 to 15% pts.wt. and at weight ratio from 4:1 to 1:4.
EFFECT: ensuring perspiration control and skin conditioning on the selected body area.
37 cl, 9 tbl, 9 ex
SUBSTANCE: tinting hairspray includes a film-forming substance, dissolvent, vitamin complex (VC), fragrance component, propellent or preservative, and, additionally ethyl acetate, and, as a vitamin complex (VC), Solutio oleosa of crystalline β-carotin that is preliminary extracted from a biomass of Blakeslea trispora mushroom, washed out in ethyl alcohol for excision of the remnants from the biomass, then the cleared crystals are dissolved in deodorised, refined sunflower, corn or olive oils.
EFFECT: high plasticity with a pronounced conditioning effect.
2 cl, 4 ex, 6 tbl
SUBSTANCE: mousse for styling damaged hair includes quaternised cationic polymer, wedding agent PEG-40 of hydrogenised castor oil, a modified corn starch, fragrance component, preservative, vitamin complex, UV-propellent and demineralised water. Additionally, it contains emulgents Cremophore A6 and Cremophore A25, and, as a vitamin complex, Solutio oleosa of crystalline β-carotin. The vitamin complex (VC) in the form of Solutio oleosa of crystalline β-carotin, contains β-carotin extracted from a biomass of mushroom Blakeslea trispora by washing with ethyl alcohol for excision of the remnants from the biomass, with the subsequent dissolution of the cleared crystals in deodorised, refined sunflower, corn or olive oils.
EFFECT: high plasticity; sun-protection properties and restoring effect after thermal styling.
2 cl, 4 ex, 6 tbl
SUBSTANCE: invention concerns cosmetology, particularly a moistening composition for cosmetic mix for hair and/or body washing, containing: natural moistening substance complex, including sodium lactate, lactic acid, glycerin, sodium chloride, sorbitol, serine, urea, allantoin and pentyleneglycol - 2.0-5.0 (mass %), grapefruit, orange, kiwi and apple juice concentrate, almond extract and malic acid in butyleneglycol solution - 2.0-5.0 (mass %), ethoxylated wheat embryo oil with addition of butyloctanol - 2.0-5.0 (mass %), water - up to 100 (mass %).
EFFECT: improved softening and moistening effect on skin and hair and reduction of skin dryness and excessive unctuosity.
2 cl, 2 tbl
FIELD: food products.
SUBSTANCE: alfalfa-based biologically active preparation (BAP) is manufactured by treatment with extraction agent and contains macro-and micronutrients, amino acids, protein, lipids, amino sugars, organic acids, carbohydrates and vitamins in the specified ratio. Method of BAP manufacturing involves grinding plant raw material, its treating with extraction agent which contains water solution of macro-and micronutrient salts, holding the extraction mixture under increased temperature and pressure with further separation, refinement and drying of the extract. Primarily plant raw material is extracted by condensate heated up to 60-80°C with mass relation of the plant raw material to the condensate equal to 1:6. Afterwards part of the extract is put into intermediate tank. The remaining part is supplied to the "hot extraction" apparatus warmed by water steam, and water solutions of macro- and micronutrients are introduced during mixing. The relation of the extract water solution to plant raw material accounts for 6:1 wt. Hot extraction is carried out under the temperature of 110-140°C and pressure 1.5 - 4.5 atm during 0.6 - 1.2 hours. Then excessive pressure is released and temperature is lowered down to 100°C. The mixture is further held for 0.2 - 0.8 hours. Then the extract is supplied for filtration and evaporation to the concentration of 45-50%. The evaporated extract is mixed with cold extract with mass relation 4.0-6.0 to 36.0. Finished mixture is bottled or dried and then packed.
EFFECT: invention allows manufacturing of a product with increased biological activity.
3 cl, 1 dwg, 13 tbl