COMPOSITIONS AND METHODS FOR REDUCING HAIR LOSS AND INCREASING HAIR GROWTH
20220008360 · 2022-01-13
Assignee
Inventors
Cpc classification
A61K9/0014
HUMAN NECESSITIES
International classification
Abstract
Method of mitigating or reversing the effect of alopecia comprising applying select aryl alkanones to those areas of the skin suffering hair thinning and/or loss/
Claims
1. A method of treating hair loss disorders and increasing hair growth in a mammalian subject, the method comprising administering to the subject a therapeutically effective amount of an aryl alkanone, in dermatologically or topically acceptable carrier, belonging to the following structure: ##STR00012##
2. The method of claim 1, wherein aryl alkanones are having IL-17 inhibitory activity, more specifically IL-17A inhibitory activity.
3. The method of claim 1, wherein one or more of the aryl alkanones are having boosting activity on growth factors linked hair growth.
4. The method of claim 3, wherein the growth factors are Platelet Derived Growth Factors (PDGF), Insulin Growth Factors (IGsl), Vascular Endothelial Growth Factors (VEGFs), Fibroblast growth factors (FGFs).
5. The method of claim 1, wherein the hair loss disorder is selected from androgenetic alopecia (AGA), non-scarring alopecia, scarring alopecia, male and female pattern AGA, alopecia areata (AA), alopecia totalis (AT), alopecia universalis (AU), eyebrow alopecia, eyelash alopecia, male pattern hair loss, female pattern hair loss, hypotrichosis, hereditary hypotrichosis simplex, frontal fibrosing alopecia, cicatricial alopecia, folliculitis decalvans, tufted folliculitis, dissecting cellulitis of the scalp, ring alopecia, chemotherapy induced alopecia, superficial or deep infections of the scalp, or tinea capitis.
6. The method of claim 1, wherein the subject is a human.
7. The method of claim 1, wherein the hair growth was observed on scalp or eyebrow after application of the present inventive composition in a dermatologically or topically acceptable vehicle.
8. The method of claim 1, wherein the inhibitor is administered locally, systemically, topically, orally, intradermally, or by injection.
9. The method of claim 1, wherein administration is to an alopecic area of the body.
10. The method of claim 1, wherein administration is to a head, a scalp, an eyebrow area, or an eyelash area of the subject.
Description
BRIEF DESCRIPTION OF THE FIGURES
[0033]
[0034]
[0035]
DETAIL DESCRIPTION OF THE INVENTION
[0036] As used in the present specification, the following terms shall have the meanings as presented:
[0037] A “dermatologically acceptable carrier” refers to a material that acts as a diluent, dispersant or carrier for the stated actives, especially the aryl alkanone(s), and is recognized in the industry as acceptable or suitable for use, preferably long term use, in skin contact and, to the extent appropriate or applicable, has been approved or is otherwise approvable by a regulatory agency of a government or governmental body or is listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use on humans.
[0038] The term “improves” or “improved” is used to convey that the method and compositions of the present teaching manifest an improvement in hair growth and health, as well as scalp health, as compared to the untreated hair and skin. In particular, it is manifest in thicker hair and/or broader hair coverage as compared to the hair and treated areas prior to the application of the claimed compositions.
[0039] The term “modulating” generally refers to the ability of the claimed compositions to down-regulate, suppress or inhibit or, alternatively, up-regulate or stimulate the expression of the mentioned genes, cytokines, growth factors and the like, as appropriate.
[0040] The term “optional” or “optionally” means that the subsequently described subject, event or circumstance may or may not occur, and that the description includes instances where the event occurs and instances where it does not and/or when the subject is present and when it is not present.
[0041] The terms “effective amount” and “hair promoting effective amount” refer to the amount of the specified compound or composition that when applied to the skin is able to affect the desired effect whether on a molecular level, as evidenced by changes in the level or concentration of targeted materials, especially cytokines and other factors, and/or on a macro level whereby visual changes are evident with respect to hair growth and thickening.
[0042] Erring on the side of caution and in an effort to avoid having overlooked or inadvertently omitted certain descriptive matter, particularly complementary and supplementary descriptive matter, it is hereby stated and affirmed that the technical publications as well as the patent and patent application publications mentioned herein are all incorporated herein in their entirety by this reference. Indeed, for example, while the current specification could present page after page of description of suitable dermatologically acceptable vehicles, supplemental or ancillary ingredients, and co-actives as well as various cosmetic and skin care compositions into which the aryl alkanones can be incorporated, such would not be productive as the same are well known and well recognized by those skilled in the art and those that come into being subsequent to the filing of this application will readily be appreciated as suitable as well
[0043] According to a first embodiment, there is provided a method of promoting and/or stimulating hair growth, particularly on the scalp, eyelids, and the eyebrow region, comprising applying to those areas of the skin, particularly the scalp, eyelids, or eyebrow region, where one desires to provide for fuller and/or healthier hair, particularly thicker hair, one or more aryl alkanones corresponding to the general Structure 1
##STR00006##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5, which may be the same or different, are independently H, OH, alkyl or alkoxy wherein the alkyl or alkoxy groups are linear or branched and have from 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms; and R.sub.6 is H, COCH.sub.3 or CO.sub.2R.sub.7, wherein R.sub.7 is a linear or branched alkyl having 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms. Most preferably, the aryl alkanone is applied topically in a carrier or as a component of a skin care and/or cosmetic composition. The composition is applied directly to the skin, particularly in those hair covered areas of the skin where thicker hair is desired or those areas of the skin where hair is missing but desired, or to the base of the hair strands, including eyebrows and eyelashes, themselves.
[0044] In accordance with a second aspect of the present teaching there is provided a method of mitigating or counteracting the effects of alopecia, said method comprising applying to those areas of the body, particularly the scalp, eyelids, and eyebrow region of the face, which are manifesting and/or suffering from alopecia an effective amount of one or more aryl alkanones corresponding to the general Structure 1
##STR00007##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5, which may be the same or different, are independently H, OH, alkyl or alkoxy wherein the alkyl or alkoxy groups are linear or branched and have from 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms; and R.sub.6 is H, COCH.sub.3 or CO.sub.2R.sub.7, wherein R.sub.7 is a linear or branched alkyl having 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms, in a dermatologically acceptable carrier.
[0045] In accordance with a third aspect of the present teaching there is provided a method of inhibiting interlueken-17 (IL-17) and/or modulating those cytokines and/or growth factors responsible for hair growth including Insulin Growth Factor 1 (IGF-1), Platelet-derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), and/or Vascular Endothelial Growth Factor (VEGF), said method comprising applying to those areas of the body in which hair growth promotion and/or stimulation is desired, particularly the scalp, eyelids, and eyebrow region of the face, an effective amount of one or more aryl alkanones corresponding to the general Structure 1
##STR00008##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Rr, which may be the same or different, are independently H, OH, alkyl or alkoxy wherein the alkyl or alkoxy groups are linear or branched and have from 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms; and R.sub.6 is H, COCH.sub.3 or CO.sub.2R.sub.7, wherein R.sub.7 is a linear or branched alkyl having 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms, in a dermatologically acceptable carrier.
[0046] In accordance with a fourth aspect of the present teaching there is provided topical compositions comprising two or more aryl alkanones corresponding to the general Structure 1
##STR00009##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5, which may be the same or different, are independently H, OH, alkyl or alkoxy wherein the alkyl or alkoxy groups are linear or branched and have from 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms; and R.sub.6 is H, COCH.sub.3 or CO.sub.2R.sub.7, wherein R.sub.7 is a linear or branched alkyl having 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms, which compositions manifest improved promotion and/or stimulation of hair growth, especially new hair growth, as compared to a composition wherein only one of the select aryl alkanones is present.
[0047] Finally, in accordance with a fifth aspect of the present teaching there is provided topical compositions comprising one or more aryl alkanones corresponding to the general Structure 1
##STR00010##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5, which may be the same or different, are independently H, OH, alkyl or alkoxy wherein the alkyl or alkoxy groups are linear or branched and have from 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms; and R.sub.6 is H, COCH.sub.3 or CO.sub.2R.sub.7, wherein R.sub.7 is a linear or branched alkyl having 1 to 8 carbon atoms, preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms, in combination with a known active for promoting or stimulating hair growth and/or new hair generation, most especially where the combination manifests an improved promotion and/or stimulation of hair growth as compared to each active individually, particularly a synergistic effect.
[0048] Preferred compounds according to Structure 1 generally fall into four groups as follows: [0049] Group A wherein R.sub.1, R.sub.2, and R.sub.5 are H and R.sub.4 is an alkyl or alkoxy group of from 1 to 8, preferably from 1 to 6, more preferably from 1 to 4 carbon atoms, most preferably OCH.sub.3, and R.sub.6 is H, COCH.sub.3 or CO.sub.2C.sub.2H.sub.5; [0050] Group B wherein R.sub.1 and R.sub.5 are H, R.sub.2 and R.sub.4 are OCH.sub.3, R.sub.3 is OH, and Re is H, COCH.sub.3 or CO.sub.2C.sub.2H.sub.5; [0051] Group C wherein R.sub.1, R.sub.2, and R.sub.5 are H, R.sub.4 is OCH.sub.3, R.sub.3 is OH, and R.sub.6 is H, COCH.sub.3 or CO.sub.2C.sub.2H.sub.5; and [0052] Group D wherein R.sub.1, R.sub.2, and R.sub.5 are H, Rand R.sub.3 are alkoxy groups, which may be the same or different, of 1 to 8, preferably, 1 to 6, more preferably 1 to 4, carbon atoms, and Re is H, COCH.sub.3 or CO.sub.2C.sub.2H.sub.5.
[0053] The most preferred aryl alkanone compounds for use in the practice of the present teaching are those compounds of Structure 2:
##STR00011##
wherein R.sub.2, R.sub.3, R.sub.4 and R.sub.6 are as described above.
[0054] Exemplary preferred aryl alkanone compounds include: [0055] Compound 1 (Acetyl Zingerone): R is H; R.sub.3 is OH; R.sub.4 is OCH.sub.3; and R.sub.6 is COCH.sub.3; [0056] Compound 2: R.sub.2 is H; R.sub.3 is OH; R.sub.4 is OCH.sub.3; and R.sub.6 is CO.sub.2C.sub.2H.sub.5; [0057] Compound 3: R.sub.2 and R.sub.4 are H; R.sub.3 is OH; and Re is COCH.sub.3; [0058] Compound 4: R.sub.2 and R are H; R.sub.3 is OH; and Re is CO.sub.2C.sub.2H.sub.5; [0059] Compound 5: R.sub.2 and R.sub.4 are OCH.sub.3; R.sub.3 is OH; and Re is COCH.sub.3; [0060] Compound 6: R.sub.2 and R.sub.4 are OCH.sub.3; R.sub.3 is OH; and Re is CO.sub.2C.sub.2H; [0061] Compound 7: R.sub.2, R.sub.3 and R.sub.4 are OCH.sub.3; and Re is COCH.sub.3; [0062] Compound 8: R.sub.2. R.sub.3 and R.sub.4 are OCH.sub.3; and Re is CO.sub.2C.sub.2H.sub.5; [0063] Compound 9: R.sub.2 and R.sub.4 are H; R.sub.3 is OCH.sub.3; and Re is CO.sub.2C.sub.2H.sub.5; [0064] Compound 10: R.sub.2 and R.sub.4 are H; R.sub.3 is OCH.sub.3; and Re is COCH.sub.3; [0065] Compound 11 (Methyl Acetyl Zingerone): R.sub.2 is H; Re and R.sub.4 are OCH.sub.3; and Re is COCH.sub.3; [0066] Compound 12 (Raspberry Ketone): R.sub.2 and R.sub.4 are H; R.sub.3 is OH; and R.sub.6 is H; and [0067] Compound 13 (Methyl Raspberry Ketone): R.sub.2 and R.sub.4 are H; R.sub.3 is OCH.sub.3; and Re is H.
[0068] Although the aryl alkanone(s) could be applied to the skin or hair directly, it is/they are typically applied as a component of a composition. Most preferably, the compositions according to the present teaching comprise the aryl alkanone in a dermatologically acceptable carrier or excipient and/or as a component of a skin or hair care product, as a component of a cosmetic composition, or as a component of a topically applied pharmaceutical composition.
[0069] Generally speaking, the aryl alkanones may be combined with/incorporated into any known carrier or base composition employed in skin or hair care/treatment compositions; especially those carriers and excipients that are suitable for long term and repeated application to the skin without manifesting sensitization or irritation or inflammation. Suitable carriers and excipients include any of the known topical excipients and like agents necessary for achieving the particular form of the skin care composition desired. Exemplary excipients include, e.g., mineral oils, silicone oils, and emulsifying agents as well as water, alcohol, or water/alcohol combinations, or other solvent(s) or solvent systems in which the aforementioned actives may be, e.g., soluble, dispersed, emulsified, etc. Preferably, though, the compositions according to the present teaching will include excipients and the like that create a substantially stable, homogenous composition and/or provide body, improved partition coefficient, and viscosity to the composition so that the aryl alkanone does not merely run off the skin once applied. Suitable carriers and carrier compositions are described at length in, for example, Gonzalez et. al.—U.S. Pat. No. 7,186,404; Aust et. al.—U.S. Pat. No. 7,175,834; Roseaver et. al.—U.S. Pat. No. 7,172,754; Simoulidis et. al.—U.S. Pat. No. 7,175,835; Mongiat et. al.—U.S. Pat. No. 7,101,536; Maniscalco—U.S. Pat. No. 7,078,022; Forestier et. al. U.S. Pat. Nos. 5,175,340, 5,567,418, 5,538,716, and 5,951,968; Deflandre et. al.—U.S. Pat. No. 5,670,140; Chaudhuri—U.S. Pat. Nos. 6,831,191, 6,602,515, 7,166,273, 6,936,735, and 6,699,463; Chaudhuri et. al.—U.S. Pat. Nos. 6,165,450 and 7,150,876; Bonda et. al. U.S. Pat. No. 6,962,692; Rodan et. al. —U.S. Pat. No. 9,144,434, Wang et. al. U.S. Pat. No. 5,830,441 and Auspitz et. al.—US 2007/0110685 A1.
[0070] The final form of these compositions and their method of manufacture depend, in part, upon the mode of administration as well as the other ingredients to be incorporated into the composition. Accordingly, the compositions containing the aryl alkanones may be in form of solutions, suspensions, emulsions, powders, creams, lotions, serums, gels, sustained-release formulations, aerosols, sprays, and the like. In following, the compositions may be prepared by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, suspending, etc. All of such options and methods are conventional in the art.
[0071] The compositions according to the present teaching as well as the compositions employed in the methods of the present teaching typically comprise the aryl alkanone(s), with or without the additional hair growth promoter, in a dermatologically acceptable carrier with the aryl alkanone being present in an effective amount. Alternatively, the aryl alkanone(s) may be incorporated into a cosmetic or hair care product including shampoos, conditioners, eyebrow fillers, moisturizing compositions, sunscreens, and the like. The aryl alkanone(s) are present in a hair promoting/hair growth stimulating effective amount, generally from 0.01 to 20, preferably from 0.05 to 10, more preferably, from 0.1 to 5, most preferably 0.1 to 2.5, weight percent, based on the total weight of the composition. Where a second, typically conventional, hair growth promoter is employed in the claimed compositions, it too is present in an amount of from 0.01 to 20, preferably from 0.05 to 10, more preferably, from 0.1 to 5, most preferably 0.1 to 2.5, weight percent, based on the total weight of the composition. Most preferably, when both the aryl alkanone(s) and a second, non-aryl alkanone hair growth promoter or stimulator are employed the amount of each is in the range of from about 0.1 to about 5 wt %, more preferably from about 0.1 to about 2.5 wt %, based on the total weight of the composition. In following, when both are present the weight ratio of the aryl alkanone(s) to the second, non-aryl alkanone hair growth or stimulating agent will vary depending upon the selection of the second, non-alkanone hair growth or stimulating agent loss, however, they will generally be present in a weight ratio of 20:1 to 1:20, preferably from 10:1 to 1:10, more preferably 5:1 to 1:5, most preferably 2:1 to 1:2.
[0072] Ideally, the combination of the aryl alkanone(s) and/or the combination of the aryl alkanone and the second, non-aryl alkanone hair growth promoter or stimulator, provides a synergistic result whereby, though the aforementioned ranges still apply, the effect of the combination in terms of improved hair thickness and/or growth is greater or more effective than for either active alone at the same level of application. In this respect, one is able to use less of the hair promotion or hair growth actives to achieve the same or better results than using the same amount of each alone. This also has the benefit of reducing the concerns or risks of sensitization, irritation, etc., while maintaining or achieving a high degree of hair loss reduction or regrowth effect.
[0073] As noted, the aryl alkanones are preferably incorporated into or combined with a carrier or other composition. Besides those mentioned above, suitable carriers also include formulated base compositions used in the preparation of, for example, scalp care health and beauty aid products, cosmetic compositions, pharmaceutical or therapeutic skin care products and the like. Such compositions have, as their primary objective, the application of the aryl alkanone(s) and, optionally, the second, non-aryl alkanone hair growth or stimulating active, for the purpose of promoting and/or stimulating hair growth. However, these compositions may be supplemented with other co-active ingredients, such as antioxidants, sunscreen actives, vitamins, anti-inflammatory agents, moisturizers, emollients, humectants, skin lighteners, anti-acne ingredients, compatible solutes and the like, and mixtures thereof, in their conventional amounts. Alternatively, or in addition thereto, these compositions may also include other ingredients that have no or little bearing upon the intended end-use or application of the treatment aspect of these compositions, but aid in the preparation and/or longevity thereof, such as solubilizers, surfactants, stabilizers, thickeners, preservatives, buffers, etc. and/or the aesthetic qualities thereof, e.g., dyes, perfumes, scents, opacifiers, colorants, etc.
[0074] Alternatively, as previously mentioned, the aryl alkanone can be incorporated into or added to existing skin and hair care products, including cosmetics, shampoos, hair conditioners, eye brow fillers, and the like where the aryl alkanone is a secondary active and/or hair growth and stimulation is a secondary consideration. This is particularly desirable as a preventative or mitigator to hair thinning and loss due to, among other causes, aging, dietary issues, pharmaceutical or their therapeutic treatments known to cause or be associated with hair thinning and/or loss, and the like.
[0075] It is impractical to attempt to list all of the ingredients which may be combined with the aryl alkanones and/or all the compositions into which the aryl alkanones may be incorporated. However, those skilled in the art will readily appreciate the same in light of the teaching hereof and the intended purpose for which the aryl alkanone is being applied.
[0076] The amount of the aryl alkanone, especially the aryl alkanone composition, to be applied is generally that amount which is sufficient to provide a thin film of the composition to the treated skin and/or to the hair, especially the roots of the hair, i.e., that portion of the hair at the skin line. Typically, a small quantity of the composition, for example from 0.1 to 5 ml, is applied to the skin/hair from a suitable container or applicator and spread over and/or rubbed into the skin using the hands or fingers or a suitable device. Preferably, the aryl alkanone composition is applied at least once, preferably at least twice, daily until the desired hair thickening/hair growth effect is attained and/or for so long as alopecia continues to manifest itself. Alternatively, the aryl alkanone composition is applied continually, as a daily ritual, to improve hair health, thickening and/or rejuvenation. In this regard, a user may adopt a routine of application of the aryl alkanone composition where the aryl alkanone is the key or a key active ingredient to address pre-existing hair thinning and/or hair loss until the desired effect is attained and then employ a hair care or cosmetic composition containing the aryl alkanone as a daily routine to maintain hair fullness and coverage and/or prevent hair loss or thinning. Although the focus of the discussion has been with the application of the compositions to the scalp, eyelid and eyebrow region, it is to be appreciated that the composition and method is applicable to any area of the body suffering from alopecia or where hair growth is desired including those specifically mentioned above as well as the pubic region, chest, underarms, etc.
[0077] Not intending to be bound thereby, it is believed that the hair growth and/or hair stimulating effect is, at least in part, a result of the down-regulation/inhibition of interleukin-17 or interaction between IL-17A and IL-17R (receptor of IL-17A) or the modulating of IL-17 downstream genes, especially those down-stream genes, that are down-regulated/inhibited or up-regulated/stimulated, respectively, by IL-17, especially IL-17A. Additionally, following on the foregoing and/or independent thereof, it is also believed that the aryl alkanones of the present teaching up-regulate/stimulate the expression of various growth factors, particularly growth factors associated with hair growth, including, but not limited to, Insulin Growth Factor 1 (IGF-1), Platelet-derived Growth Factor β (PDGFβ), Platelet-derived Growth Factor α (PDGFα), Fibroblast Growth Factor 1 and 7 (FGF-1 and 7), Vascular Endothelial Growth Factor (VEGF) by the specified aryl alkanones. Accordingly, it is believed that actives that influence these factors as well as concentrates, such as platelet concentrates, that contain these factors will act synergistically with the aryl alkanones of the present teaching. Other influencing factors and agents to be used in combination with the aryl alkanones, besides those already mentioned herein, include, but are not limited to, isosorbide esters, especially the diesters and linoleic acid esters and similar compounds as disclosed in, e.g., U.S. Pat. Nos. 8,496,917; 9,636,321 and 10,597,402, the contents of which are incorporated herein by reference, as well as various plant extracts including terminalia chebula extract, Phyllanthus embilica extract, and the like.
[0078] Preferred co-actives are ones providing a linoleic component to the composition, especially, one or more of linoleic acid, alinoleic ester, a linoleic glycoside and/or a linoleic glyceride, especially a triglyceride. Especially preferred is linoleic acid and/or a short chain, C.sub.1 to C.sub.8, esters, most especially ethyl linoleate. Alternatively, especially owing to their availability, ease of formation and use, and cost, one may use one or more long chain fatty acid, ester, glycoside and/or glyceride compositions having a high linoleic content, particularly those wherein the linoleic content is at least 30%, preferably at least 40%, more preferably at least 45%, by weight, or even higher levels such as at least 50%, preferably at least 60%, more preferably at least 65%, by weight. Generally speaking, the long chain fatty acids are characterized as having from 14 to 22 carbon atoms and may be saturated or unsaturated. As noted, their esters, especially short chain esters, as noted above, glycosides, and glycerides, especially triglycerides, are also suitable and efficacious as are combinations thereof with each other and/or with the long chain fatty acids. Furthermore, one may enhance the linoleic content of long chain fatty acid, ester, glycoside and/or glyceride compositions by adding one or more of linoleic acid, a linoleic ester, a linoleic glycoside and a linoleic glyceride.
[0079] Additionally, while one may, and may preferably, elect to use the individual linoleic compounds noted above, or combinations thereof, it is more typical to employ fatty acid oils obtained or derived from natural sources containing high levels of the linoleic compounds. Suitable oils include those disclosed in Orsavova, J. et. al., “Fatty Acids Composition of Vegetable Oils and Its Contribution to Dietary Energy Intake and Dependence of Cardiovascular Mortality on Dietary Intake of Fatty Acids,” Int. J. Mol. Sci. 2015, 16, 12871-12890, which is incorporated herein by reference, especially the oils isolated from safflower, grape seed, Silybum marianum, hemp, sunflower, wheat germ, pumpkin seed, sesame, rice bran, almond, rapeseed, peanut, olive, and coconut. Table 1 presents the breakdown of the oleic acid, linoleic acid and linolenic acid content (% by weight) of some of the more preferred oils.
TABLE-US-00001 TABLE 1 Source of natural oils and typical fatty acid cornpositions* Oils Oleic Acid Linoleic Acid Linolenic Acid Safflower 8-21 68-83 <0.5 Grapeseed 12-25 60-75 ~0.2 Rosehip 14-16 43-46 31-34 Sunflower typical 14-40 48-74 ~0.4 Sunflower special ~85 ~6 <0.5 Hemp ~10 ~52 ~10 Walnut 26-35 45-60 <1 Sesame 35-50 35-50 <1% Evening Primrose 5-11 70-77 <1% Soybean 17-30 48-58 5-11 Wheat-germ 12-23 52-59 3-10 *Reference: https://essentialoils.co.za/rosehip-analysis.htm
[0080] As noted, these natural oils are comprised of a plurality of different fatty acids, oftentimes a combination of unsaturated, mono-saturated and/or polyunsaturated long chain fatty acids. The oils may be used as is or further purified to isolate specific long chain fatty acids or mixtures thereof. Suitable fatty acid esters may be obtained by esterifying with wide range of alcohols, such methanol, ethanol, propanol, butanol, pentanol, hexanols, etc. and are also available commercially. Similarly, suitable fatty acid glycerides may be obtained by esterifying the long chain fatty acids with glycerol. Of course, it is to be appreciated that the long chain fatty acid, ester and glyceride compositions may contain other fatty acids and esters, particularly where they are already present in the starting materials.
EXAMPLES
[0081] Having described the invention in general terms, the following sets of examples will now demonstrate various embodiments of the inventive compositions and their use. In the following examples, unless otherwise indicated, all temperatures are set forth in degrees Celsius and all parts and percentages are by weight based on the total composition as applied to the scalp or eyebrow.
Example 1
[0082] A scalp serum (Composition 1) according to the present teaching was prepared having the composition as presented in Table 2.
TABLE-US-00002 TABLE 2 Composition 1 INCI name Trade Name/Supplier % w/w Phase A Water 62.15 Panthenol Ritapan DL, 50%/Rita 1.00 Niacinamide Niacinamide/DSM 1.00 Denatured Alcohol Denatured/Alcohol/ 15.00 Quality Chemical Polyquaternium-10 Ritaquta 3000/Rita 0.75 Butylene Glycol Jeechem Bugl/Jeen 4.00 Glycerin Glycerin/Jeen 3.00 Dehydroacetic Acid & Benzyl Geogard 221/Lonza 1.00 Alcohol Trisodium Ethylenediamine Natrlquest E30/Innospec 0.10 Disuccinate Phase B Ethoxydiglycol Transcutol CG/Gattefosse 8.00 Acetyl Zingerone (Compound 1) Synoxyl ® AZ/Sytheon/ 2.00 Present invention Rasberry Ketone (Compound 12) Synoxyl ® RK/Sytheon/ 2.00 Present invention Total 100.00
[0083] Composition 1 was prepared by weighing each of the components of Phase A and combining them in a main kettle equipped with a homogenizer and heating, while mixing, to 50-55° C. Similarly, each of the components of Phase B were weighed and combined in a side kettle and heat with mixing to 45° C. Mix was continued in each kettle until all solids were dissolved. When both phases attained the proper temperature and were uniform, Phase B was added to Phase A and the combination mixed for 10-15 minutes. The resulting composition was found to have a pH 5.0 to 5.5.
Example 2
[0084] A second scalp serum (Composition 2) according to the present teaching was prepared having the composition as presented in Table 3, Composition 2A having Acetyl Zingerone (Compound 1) and Composition 2B having Methyl Acetyl Zingerone (Compound 11). These compositions were prepared according to the same procedure as Composition 1.
TABLE-US-00003 TABLE 3 Compositions 2A and 2B INCI name Trade Name/Supplier % w/w Phase A Water 64.15 Panthenol Ritapan DL, 50%/Rita 1.00 Niacinamide Niacinamide/DSM 1.00 Polyquaternium-10 Ritaquta 3000/Rita 0.75 Butylene Glycol Jeechem Bugl/Jeen 4.00 Glycerin Glycerin/Jeen 3.00 Water & Sodium Benzoate & Euxyl K 712/Schulke 1.00 Potassium Sorbate Phase B Ethoxydiglycol Transcutol CG/Gattefosse 23.00 Acetyl Zingerone (Compound 1) Synoxyl ® AZ/Sytheon/Present 2.00 or or invention or 2.00 Methyl Acetyl Zingerone Synoxyl ® (Compound 11) inventionMAZ/Sytheon/Present Total 100.00
Example 3
[0085] An evaluation of the compositions according to the present teaching were applied to three male subjects to evaluate their effect in promoting hair growth and rejuvenation as follows: [0086] Composition 1 was applied to the scalp of an African American individual (44 yrs. old male) twice a day for three months. He had been experiencing hair loss and had been bald for the last five years. He shows receding hairline on the front of the head and loss of hair on the crown of the head. He doesn't have any underlying skin conditions like eczema. Prior to the application of the Composition 1, the individual had applied Rogaine for a period of four months, but failed to see any growth. When using both Rogain and Composition simultaneously, significant hair growth and thickening was manifest as shown in
Example 4—Gene Assay—IL-17A Impact
[0089] As noted in the Background, interleukin 17 (IL-17), particularly interleukin-17A (IL-17A), is believed to have a role in alopecia and its manifestation. In an effort to understand the possible effect of the aryl alkanones in impacting the effect of IL-17A, a microarray study was performed using RNA from EpiDerm FT (RHE) tissues (Mattek. Ashland, Mass.). In the experiment, standard methods of tissue processing and RNA extraction were followed. RNA obtained from cultures following 24 hours of exposure to acetyl zingerone (AZ-Compound 1) were analyzed using Agilent human 8X60K arrays (AZ, n=2; CTL, n=2). Microarray processing, normalization, quality control, probe annotation, probe filtering, differential expression testing, and motif/annotation enrichment analysis steps are followed as described in the literature (WR Swindell et al. Psoriasis drug development and GWAS interpretation through in silico analysis of transcription factor binding sites, Clinical and translational medicine, 4:13, 2015). As shown in
Example 5—Growth Factor Effect
[0090] A series of experiments were conducted to evaluate the effect on various aryl alkanones on several genes/growth factors specific to hair growth. Human hair follicle dermal papilla cell (HFDPC, lot #2905, cat.#602K-05a, obtained from a 46 year old Caucasian female) were purchased from Cell Applications, San Diego, Calif.) and were grown in the supplier-recommended medium until subconfluence. Cells were then seeded at 75,000/well in the 24 well plates and the next day they were exposed to different dilutions of test materials and their combinations. The treated culture were maintained for 24 h, after which they were observed through a Nikon inverted microscope. The cells were harvested and rinsed and RNA was extracted and purified with RNeasy Plus Mini kit cat. #74134 from Qiagen, (Germantown, Md.), using QiaCube Connect robotic station (Qiagen). Purified total RNA was assessed at 260 nm and 280 nm with NanoDrop Lite (Thermo Fisher Scientific, Waltham, Mass.). cDNA was prepared using High-Capacity RNA-to-cDNA™ Kit from Applied BioSystems (Carlsbad, Calif.) and the expression of the genes of interest, specifically IGF-1 and PDGFβ,) was measured by real-time quantitative PCR with BioRad iCycler iQ Detection System using TaqMan primer assays with FAM-labeled probes from Applied BioSystems and Azura 2×Taq Mix Master (Azura Genomics, Raynham, Mass.). Efficiency ΔΔCt method was used for quantification of results, after the normalization of gene expression to 18S (the housekeeping gene). Genes were considered differentially expressed if they were detected in at least one triplicate average (<50 cycles to detection), the p value, as determined by the two-tailed t-test, was ≤0.05 and the modulation was 22.0. To establish the optimal methods, multiple experiments were performed.
[0091] Table 4 presents the results of this study. The results are presented as the fold change (FC) of the expression of the indicated gene as compared to the water control: water being normalized. The results are considered statistically significant when p=<0.05. As shown in Table 4, the aryl alkanones, with the exception of raspberry ketone (RK) at low level, provided a marked upregulation of each of the growth factors, whereas the comparative compound, zingerone, manifested no effect. Accordingly, it is believed that an up-regulation of the various growth factors associated with hair growth may account for the hair growth and thickening realized by the use of the aryl alkanones of the present teaching. Although the results obtained with the combination of RK and AZ and RK and MAZ suggested a dilution or reduction in the effect of AZ and MAZ alone, the actual marked improvement in hair growth and thickening realized by the combination in Example 3 suggests that other growth factors may be more optimally up-regulated by RK and its combination with AZ and MAZ.
TABLE-US-00004 TABLE 4 Test Material P value IGF-1 p value PDGFB Water Control 1 100 1 100 Zingerone 50 ug/ml No effect No effect Zingerone 200 ug/mL No effect No effect AZ + RK 50 + 50 ug/mL No effect 0.034 2.2 MAZ + RK 100 + 100 ug/mL No effect 0.000 4.0 Raspberry Ketone (RK) No effect No effect 50 ug/mL Raspberry Ketone (RK) No effect 0.054 1.7 100 ug/mL Acetyl Zingerone (AZ) 0.000 5.3 0.000 7.0 50 ug/mL Acetyl Zingerone (AZ) 0.000 5.5 0.000 3.0 100 ug/mL Acetyl Zingerone (AZ) 0.004 7.5 Not done 200 ug/mL Methyl Acetyl Zingerone 0.002 4.9 0.009 46 (MAZ) 50 ug/mL Methyl Acetyl Zingerone (MAZ) 0.000 8.0 0.001 5.7 100 ug/mL Methyl Acetyl Zingerone (MAZ) 0.000 3.7 0.002 3.2 200 ug/mL
Example 6—Hair and Scalp Conditioner
[0092] In Examples 1 and 2, serum formulations were prepared for direct application to stimulate and promote hair growth, particularly for those suffering from alopecia areata. While those compositions are also efficacious and suitable for use on those individuals suffering from androgenetic alopecia, modified traditional hair care formulations are an alternative way to deliver the active for promoting growth, particularly for those in the early stages of androgenetic alopecia, particularly where large bald areas have yet to manifest. In following there is provided a hair and scalp condition formulated according to the formulation provided in Table 5. This formulation is prepared according to conventional general methodologies which typically comprises individually preparing Phases A and B and then combining the two and allowing the combined formulation to hydrate. Separately Phase C is prepared and heated to 80° C. After fully hydrating the combination of Phases A and B, the combination is heated to 75° C. and Phase C is gradually added while mixing. The mixture is then cooled under propeller agitation until cooled to 40° C. Meanwhile, Phase D is separately prepared and, once the combination of Phase A, B and C is cooled, Phase D is added to the mixture while maintaining mixing until uniform.
TABLE-US-00005 TABLE 5 Hair and Scalp Conditioner INCI name % w/w Phase A Water (demineralized) 82.00 Phase B Hydroxyethylcellulose 1.00 Glycerin 2.00 Cetrimonium Chloride 0.50 Phenoxyethanol 1.00 Potassium Sorbate 0.25 Phase C Glycery Stearate 1.00 Cetary Alcohol 5.00 Cetyl Esters 0.50 Behentrimonium Chloride 1.00 lsosorbide Dicaprylate 2.00 Caprylic/Capric Triglyceride 0.50 PEG-8 1.00 Aryl Alkanone of Structure 1 0.50 Phase D Panthenyl Hydroxypropyl 0.30 Steardimonium Chloride Panthenol 0.30 Hydrolyzed Rice Protein 1.00 Sodium Hydroxide 0.15
[0093] Any of the aryl alkanones according to Structure 1, preferably of Structure 2, can be employed in the hair and scalp conditioner. Most preferably the aryl alkenone is acetyl zingerone, methyl acetyl zingerone, raspberry ketone, methyl raspberry ketone and combinations of any two, three or all four.
Example 7: Sunscreen Spray
[0094] One of the issues with alopecia of the scalp is that the scalp becomes more susceptible to sunburn. Accordingly, it is strongly recommended to apply a sunscreen to the scalp to protect it from sun damage. According to this example there is prepared a sunscreen spray formulation which not only protects against sunburn but also promotes hair growth and thickening. The exemplary formulation is presented in Table 6 and is prepared by preparing Phase A and a pre-mix of Phase B, the latter being heated to 75° C. with mixing until it is completely free of solids. Phases Aand C are then added to phase B at 50° C. with continued mixing.
TABLE-US-00006 TABLE 6 Broad spectrum clear spray sunscreen INCI name Trade Name/Supplier % w/w Phase A Ethanol Ethanol 39.00 VA/Butyl Maleate/lsobornyl Acrylate Advantage Plus/Ashland 2.00 Copolymer Phase B Avobenzone Eusolex 9020/EMD 3.00 Trimethoxybenzylidene Pentanedione* Synoxyl ® HSS/Sytheon 2.50 Homosalate Eusolex HMS/EMD 10.00 Octyl Salicylate Eusolex OS/EMD 5.00 Aryl Akanone 1.00 PEG-8 PEG 400/Acme 5.00 Diisopropyl Adipate Dermol DIA/Alzo 5.00 Phase C Phenethyl Benzoate X-tend 226/Ashland 20.50 C12-15 Alkyl Benzoate Finsolv TN/Innospec 5.00 Isosorbide Dicaprylate HydraSynol ™ DOI/Sytheon 2.00 Total 100.00 *Trimethoxy benzylidene Pentanedione is as photostabilizer and in-vivo SPF booster. This can be replaced with Octocrylene or Diethylhexyl syringylidene malonate or Ethylhexyl mothocycrylene
[0095] As with the hair and scalp conditioner of Example 6, any of the aryl alkanones according to Structure 1, especially Structure 2, can be employed in the instant sunscreen composition. Most preferably the aryl alkenone is acetyl zingerone, methyl acetyl zingerone, raspberry ketone, methyl raspberry ketone and combinations of any two, three or all four.
Example 8: Broad Spectrum Sunscreen Spray
[0096] A second, broad spectrum sunscreen spray formulation for use in the practice of the present teaching is of the formulation presented in Table 7. This product is produced in the same manner as the sunscreen composition of Example 7. Once again, as in Example 7, any of the aryl alkanones according to Structure 1, especially Structure 2, may be employed in the instant broad spectrum sunscreen spray. Most preferably the aryl alkenone is acetyl zingerone, methyl acetyl zingerone, raspberry ketone, methyl raspberry ketone and combinations of any two, three or all four.
TABLE-US-00007 TABLE 7 Broad spectrum clear spray sunscreen INCI name Trade Name/Supplier % w/w Phase A Ethanol Ethanol 39.00 VA/Butyl Maleate/lsobornyl Acrylate Advantage Plus/Ashland 2.00 Copolymer Phase B Avobenzone Eusolex 9020/EMD 3.00 Trimethoxybenzylidene Pentanedione Synoxyl ® HSS/Sytheon 2.50 Homosalate Eusolex HMS/EMD 10.00 Octyl Salicylate Eusolex OS/EMD 5.00 PEG-8 PEG 400/Acme 8.00 Diisopropyl Adipate Dermal DIA/Alzo 2.00 Phase C Phenethyl Benzoate X-tend 226/Ashland 20.50 C12-15 Alkyl Benzoate Finsolv TN/Innospec 5.00 Isosorbide Disunflowerseedate HydaSynol ™ IDL/Sytheon 2.00 Total 100.00
[0097] The patents, patent publications and other documents cited herein, including any cross-referenced or related patent or patent applications, are hereby incorporated herein by reference in their entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is pertinent prior art with respect to any invention disclosed or claimed herein or that it alone, or in combination with any other citation or combination of citations, teaches, suggests or discloses any such invention. Further, to the extent that any meaning or definition expressly applied to a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.
[0098] The various embodiments described above are provided by way of illustration only and should not be construed as or deemed to limit the claims attached hereto. The present invention can suitably comprise, consist of, or consist essentially of, any of the disclosed or recited elements. Thus, the invention illustratively disclosed herein can be suitably practiced in the absence of any element, which is not specifically disclosed as being required herein. Furthermore, various modifications and changes to the teachings herein will be recognized by those skilled in the art having the benefit of the present teachings and may be made to the present teachings without departing from the true spirit and scope of the invention as claimed and are, hence, deemed and to be deemed within the full scope of the appended claims.