Abstract: The present disclosure relates to a composition comprising L-histidine and a dipeptide which at specific w/w ratio is able to delay the process of aging. Also provided are the methods of preparation and usage of the same.
FIELD OF INVENTION
[001] The present disclosure relates to the field of cosmetic formulations in general and compositions for the inhibition of skin aging in particular. There is provided a 5 composition comprising L-histidine and a dipeptide to address the problem of skin aging.
BACKGROUND OF THE INVENTION
[002] Human Skin undergoes chronological and progressive aging as a consequence
of both genetic as well as environmental factors. Extrinsic factors coupled with 10 intrinsic factors accelerate the process of skin aging and lead to major clinical
manifestations such as thinning, sagging, pigmentation and wrinkling.
[003] Skin being the outermost layer of the body is subjected to continuous attrition
which results in the degradation of ECM (Extra cellular matrix) and ultimately in the
deterioration of skin quality. 15 [004] One of the important parameters that contributes to a healthy skin is the
moisture content of the skin. A stressful lifestyle coupled with exposure to various
environmental factors such as sunlight and chemicals results in reduction of total
moisture content that further leads to thinning and sagging of skin. External factors
such as UV irradiation from the sun has deleterious effect on human skin, including 20 sun burn, immune suppression, cancer and premature aging (Gary J. et al., N. Engl. J.
Med., 1997; 337:1419-1429). According to a research by Potts RO et al. aged skin
has a lower water content than the skin of the younger men.
[005] US20040033246A1 features a composition comprising L-histidine and other
active ingredients for prevention of skin aging. 25 [006] US20060286046A1 describes a composition containing N-acetylcysteine and
L-carnosine for countering the effects of skin aging.
[007] US20100272790A1 reveals a composition comprising of a lipoic acid, a carnitine and a carnosine for treating skin.
[008] Although various studies have been performed with respect to the identification of compositions which possess anti-aging properties that aid in the 5 inhibition of the natural and premature skin aging, there still remains a requirement for better and safer options.
SUMMARY OF INVENTION
[009] In an aspect of the present disclosure, there is provided a composition 10 comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2- 2:1. 15 [0010] In an aspect of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-20 0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2- 2:1.
[0011] In an aspect of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and 25 (ii) at least one dipeptide; and (c) contacting said composition with skin, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging.
[0012] These and other features, aspects, and advantages of the present subject matter
will be better understood with reference to the following description and appended
claims. This summary is provided to introduce a selection of concepts in a simplified
form. This summary is not intended to identify key features or essential features of
5 the claimed subject matter, nor is it intended to be used to limit the scope of the
claimed subject matter.
BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS
[0013] The following drawings form a part of the present specification and are
included to further illustrate aspects of the present disclosure. The disclosure may be
0 better understood by reference to the drawings in combination with the detailed description of the specific embodiments presented herein.
[0014] Figure 1 shows the effect of the combination of L-histidine (H), and L-carnosine (C) on mitochondrial membrane potential at weight percentage of 0.05% L-histidine and 0.1% L-carnosine (H+C), in accordance with an embodiment of the
5 present disclosure.
[0015] Figure 2 shows the effect of the combination of L-histidine (H), and L-carnosine (C) on mitochondrial membrane potential at weight percentage of 0.1% L-histidine and 0.2% L-carnosine (H+C), in accordance with an embodiment of the present disclosure.
0 [0016] Figure 3 shows the effect of the combination of L-histidine (H), and L-carnosine (C) on mitochondrial membrane potential at weight percentage of 0.025% L-histidine and 0.05% L-carnosine (H+C), in accordance with an embodiment of the present disclosure.
DETAILED DESCRIPTION OF THE INVENTION
5 [0017] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be
understood that the present disclosure includes all such variations and modifications.
The disclosure also includes all such steps, features, compositions, and compounds
referred to or indicated in this specification, individually or collectively, and any and
all combinations of any or more of such steps or features. 5 Definitions
[0018] For convenience, before further description of the present disclosure, certain
terms employed in the specification, and examples are delineated here. These
definitions should be read in the light of the remainder of the disclosure and
understood as by a person of skill in the art. The terms used herein have the meanings 10 recognized and known to those of skill in the art, however, for convenience and
completeness, particular terms and their meanings are set forth below.
[0019] The articles “a”, “an” and “the” are used to refer to one or to more than one
(i.e., to at least one) of the grammatical object of the article.
[0020] The terms “comprise” and “comprising” are used in the inclusive, open sense, 15 meaning that additional elements may be included. It is not intended to be construed
as “consists of only”.
[0021] Throughout this specification, unless the context requires otherwise the word
“comprise”, and variations such as “comprises” and “comprising”, will be understood
to imply the inclusion of a stated element or step or group of element or steps but not 20 the exclusion of any other element or step or group of element or steps.
[0022] The term “including” is used to mean “including but not limited to”.
“Including” and “including but not limited to” are used interchangeably.
[0023] L-histidine is an essential α-amino acid used in the biosynthesis of proteins.
The production of this amino acid is reduced in our body and hence it is 25 primarilytaken in through diet. It has many vital functions within the body and is
involved in the synthesis of haemoglobin, tissue repair and strengthening of the
immune system (aminoacidstudies.org).
[0024] L-carnosine is a dipeptide molecule which is made up of beta alanine and
histidine amino acids. It has capability to protect cells and tissues from free radicals.
[0025] Mitochondrial membrane potential is the difference in electric potential between the interior and exterior of mitochondria. The transmembrane potential of the mitochondria drives the production of ATP.
[0026] Carriers are substances that serve as mechanisms to improve the delivery and 5 the effectiveness of the drug.
[0027] A diluent (also referred to as filler, dilutant, or thinner) is a diluting agent. [0028] An excipient is an inactive substance that serves as a vehicle or medium for a drug or other active substance. Excipients include colouring agents, humectants, preservatives, emollients and combinations thereof.
10 [0029] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described. All publications mentioned
15 herein are incorporated herein by reference.
[0030] Natural skin aging is an inevitable process that leads to the loss of cellular integrity and functioning. One of the factors needed to maintain the youthfulness of skin is the maintenance of mitochondrial function. Mitochondria are responsible for the production of adenosine triphosphate (ATP), which is the energy currency of a cell
20 as drives major metabolic interactions within the body. ATP is also an essential molecule in regulating DNA repair mechanisms, which is essential for the renewal of the cells of the skin. The potential across the mitochondrial membrane is responsible for the production of ATP-the currency of energy. Due to cellular senescence over a period of time there is loss in the mitochondrial membrane potential and thus a decline
25 in the yield of ATP. Thus, altering mitochondrial dynamics can cause mitochondrial defects and subsequently affect the process involved in maintaining the skin. The composition disclosed herein of L-histidine and a dipeptide provides a solution to address skin aging by protection of mitochondrial membrane potential.
[0031] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only. Functionally-equivalent products, compositions, and methods are clearly within the scope of the disclosure, as described herein. 5 [0032] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range
10 of 1:2-2:1.
[0033] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and
15 L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0034] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in
20 said composition is 1:2.
[0035] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%,
25 the at least one dipeptide weight percentage in said composition is in the range of
0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said
composition is in the range of 1:2-2:1.
[0036] In an embodiment of the present disclosure, there is provided a composition
comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one
7
dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. 5 [0037] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one 10 dipeptide w/w ratio in said composition is 1:2.
[0038] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-15 histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0039] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is carnitine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said 20 composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. [0040] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is carnitine, L-histidine weight percentage in said composition is in the 25 range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [0041] In an embodiment of the present disclosure, there is provided a composition
comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one
8
dipeptide is carnitine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [0042] In an embodiment of the present disclosure, there is provided a composition 5 comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. 10 [0043] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one 15 dipeptide w/w ratio in said composition is 1:2.
[0044] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is dipeptide-2, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-20 histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0045] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-25 carnosine w/w ratio in said composition is in the range of 1:2-2:1.
[0046] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight
percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2.
[0047] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight 5 percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, and L-histidine to L-carnosine w/w ratio in said composition is 2:1.
[0048] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at
10 least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. [0049] In an embodiment of the present disclosure, there is provided a composition
15 comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
20 [0050] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said
25 composition is 1:2.
[0051] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-
histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. 5 [0052] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range 10 of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[0053] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-15 carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0054] In an embodiment of the present disclosure, there is provided a composition 20 comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. 25 [0055] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said
composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is in the range of 1:2-2:1.
[0056] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one 5 diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2. [0057] In an embodiment of the present disclosure, there is provided a composition
10 comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2. [0058] In an embodiment of the present disclosure, there is provided a method of
15 preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said
20 composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. [0059] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one
25 dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said
composition, wherein L-histidine weight percentage in said composition is in the
range of 0.03%-0.09%, the at least one dipeptide weight percentage in said
composition is in the range of 0.06%-0.18%, and L-histidine to the at least one
dipeptide w/w ratio in said composition is 1:2.
12
[0060] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said 5 composition, wherein L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [0061] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide,
10 said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said composition, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight
15 percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. [0062] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one
20 dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range
25 of 1:2-2:1.
[0063] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide,
said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one
dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said
13
composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. 5 [0064] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; and (c) contacting L-histidine and the at least one dipeptide to obtain said composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight
10 percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0065] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) L-carnosine, said method
15 comprising: (a) obtaining L-histidine; (b) obtaining L-carnosine; and (c) contacting L-histidine and L-carnosine to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is in the range of 1:2-2:1.
20 [0066] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) L-carnosine, said method comprising: (a) obtaining L-histidine; (b) obtaining L-carnosine; and (c) contacting L-histidine and L-carnosine to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight
25 percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2.
[0067] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) L-carnosine, said method
comprising: (a) obtaining L-histidine; (b) obtaining L-carnosine; and (c) contacting L-14
histidine and L-carnosine to obtain said composition, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition 0.1%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2. 5 [0068] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining
10 the at least one excipient; and (f) contacting L-histidine, the at least one dipeptide, the at least one carrier, the at least one diluent and the at least one excipient to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one
15 dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[0069] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; (c)
20 obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one excipient; and (f) contacting L-histidine, the at least one dipeptide, the at least one carrier, the at least one diluent and the at least one excipient to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said
25 composition is in the range of 0.06%-0.18%, and L-histidine to the at least one
dipeptide w/w ratio in said composition is 1:2.
[0070] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at
least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method
15
comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one excipient; and (f) contacting L-histidine, the at least one dipeptide, the at least one carrier, the at least one diluent and the at least one excipient to obtain said 5 composition, wherein L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [0071] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at
10 least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one excipient; and (f) contacting L-histidine, the at least one dipeptide, the at least one carrier, the at least one diluent and the at least one excipient to obtain said
15 composition, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
20 [0072] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining
25 the at least one excipient; and (f) contacting L-histidine, the at least one dipeptide, the
at least one carrier, the at least one diluent and the at least one excipient to obtain said
composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight
percentage in said composition is in the range of 0.03%-0.09%, the at least one
dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and
16
L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[0073] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) the 5 at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one excipient; and (f) contacting L-histidine, the at least one dipeptide, the at least one carrier, the at least one diluent and the at least one excipient to obtain said
10 composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [0074] In an embodiment of the present disclosure, there is provided a method of
15 preparing a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining the at least one dipeptide; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one excipient; and (f) contacting L-histidine, the at least one dipeptide, the
20 at least one carrier, the at least one diluent and the at least one excipient to obtain said composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
25 [0075] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) L-carnosine; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining L-carnosine; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one
excipient; and (f) contacting L-histidine, the L-carnosine, the at least one carrier, the at least one diluent and the at least one excipient to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and 5 L-histidine to L-carnosine w/w ratio in said composition is in the range of 1:2-2:1.
[0076] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) L-carnosine; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining L-carnosine; (c) obtaining the at
10 least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one excipient; and (f) contacting L-histidine, L-carnosine, the at least one carrier, the at least one diluent and the at least one excipient to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and
15 L-histidine to L-carnosine w/w ratio in said composition is 1:2.
[0077] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; (ii) L-carnosine; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, said method comprising: (a) obtaining L-histidine; (b) obtaining L-carnosine; (c) obtaining the at
20 least one carrier; (d) obtaining the at least one diluent; (e) obtaining the at least one excipient; and (f) contacting L-histidine, L-carnosine, the at least one carrier, the at least one diluent and the at least one excipient to obtain said composition, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, and L-histidine to L-carnosine w/w ratio in
25 said composition is 1:2.
[0078] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide,
said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a
solution B of the at least one dipeptide; and (c) contacting solution A and solution B
18
to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. 5 [0079] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein L-histidine weight percentage in said composition
10 is in the range of 0.03%-0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0080] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide,
15 said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein L-histidine weight percentage in said composition is 0.05%, the at one least dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
20 [0081] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein the at least one dipeptide is selected from a group
25 consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[0082] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B 5 to obtain said composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. 10 [0083] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein the at least one dipeptide is L-carnosine, L-15 histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0084] In an embodiment of the present disclosure, there is provided a method of 20 preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide 25 weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[0085] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) L-carnosine, said method
comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of L-20
carnosine; and (c) contacting solution A and solution B to obtain said composition, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is in the range of 5 1:2-2:1.
[0086] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) L-carnosine, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of L-carnosine; and (c) contacting solution A and solution B to obtain said composition,
10 wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2. [0087] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) L-carnosine, said method
15 comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of L-carnosine; and (c) contacting solution A and solution B to obtain said composition, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2.
20 [0088] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein said solution A is prepared in an organic solvent.
25 [0089] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B
to obtain said composition, wherein said solution A is prepared in an inorganic solvent.
[0090] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, 5 said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein said solution B is prepared in an organic solvent. [0091] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (i) L-histidine; and (ii) at least one dipeptide, 10 said method comprising: (a) obtaining a solution A of L-histidine; (b) obtaining a solution B of the at least one dipeptide; and (c) contacting solution A and solution B to obtain said composition, wherein said solution B is prepared in an inorganic solvent.
[0092] In an embodiment of the present disclosure, there is provided a method of 15 inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and (ii) at least one dipeptide; and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said 20 composition is in the range of 1:2-2:1, and said composition inhibits skin aging.
[0093] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and (ii) at least one dipeptide; and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is in the range of 0.03%-25 0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging. [0094] In an embodiment of the present disclosure, there is provided a method of
inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-22
histidine; and (ii) at least one dipeptide; and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is 0.05%, the at one least dipeptide weight percentage in said composition is 0.0.1%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin 5 aging.
[0095] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and (ii) at least one dipeptide; and (b) contacting said composition with skin, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, 10 carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging. 15 [0096] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and (ii) at least one dipeptide; and (b) contacting said composition with skin, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight 20 percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging.
[0097] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-25 histidine; and (ii) at least one dipeptide; and (b) contacting said composition with skin, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at
least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging.
[0098] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-5 histidine; and (ii) at least one dipeptide; and (b) contacting said composition with skin, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging. 10 [0099] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and (ii) L-carnosine; and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, L-15 histidine to L-carnosine w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging.
[00100] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and (ii) L-carnosine; and (b) contacting said composition with skin, wherein 20 L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging.
[00101] In an embodiment of the present disclosure, there is provided a method of 25 inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; and (ii) L-carnosine; and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, L-histidine to L-carnosine w/w ratio in said
composition is 1:2, and said composition inhibits skin aging.
24
[00102] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein 5 L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging.
[00103] In an embodiment of the present disclosure, there is provided a method of 10 inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-15 0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging.
[00104] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; 20 and (v) at least one excipient, and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is 0.05%, the at one least dipeptide weight percentage in said composition is 0.1%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging. 25 [00105] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein
the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine,
25
and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging. 5 [00106] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said 10 composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging.
[00107] In an embodiment of the present disclosure, there is provided a method of 15 inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight 20 percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging.
[00108] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-25 histidine; (ii) at least one dipeptide; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said
composition is 0.1%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging.
[00109] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-5 histidine; (ii) L-carnosine; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to L-carnosine w/w ratio in said composition is in the range of 1:2-2:1, and said
10 composition inhibits skin aging.
[00110] In an embodiment of the present disclosure, there is provided a method of inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) L-carnosine; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein L-histidine
15 weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging. [00111] In an embodiment of the present disclosure, there is provided a method of
20 inhibiting skin aging comprising: (a) obtaining a composition comprising: (i) L-histidine; (ii) L-carnosine; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient, and (b) contacting said composition with skin, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, L-histidine to L-carnosine w/w ratio in said composition is
25 1:2, and said composition inhibits skin aging.
[00112] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-
histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential.
[00113] In an embodiment of the present disclosure, there is provided a composition 5 comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential.
10 [00114] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the
15 mitochondrial membrane potential.
[00115] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%,
20 the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. [00116] In an embodiment of the present disclosure, there is provided a composition
25 comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide
w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential.. [00117] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one 5 dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. 10 [00118] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition 15 inhibits skin aging by maintaining the mitochondrial membrane potential.
[00119] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to L-20 carnosine w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. [00120] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight 25 percentage in said composition is in the range of 0.06%-0.18%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. [00121] In an embodiment of the present disclosure, there is provided a composition
comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight
29
percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. 5 [00122] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at one least dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at
10 least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. [00123] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage
15 in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. [00124] In an embodiment of the present disclosure, there is provided a composition
20 comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential.
25 [00125] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at
30
least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential. 5 [00126] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range
10 of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential.
[00127] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at
15 least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the
20 mitochondrial membrane potential.
[00128] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one
25 dipeptide weight percentage in said composition is 0.1%, L-histidine to the at least
one dipeptide w/w ratio in said composition is 1:2, and said composition inhibits skin
aging by maintaining the mitochondrial membrane potential.
[00129] In an embodiment of the present disclosure, there is provided a composition
comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one
31
diluent; and (e) at least one excipient, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, L-histidine to L-carnosine w/w ratio in said composition is in the range of 1:2-2:1, and said composition inhibits skin aging 5 by maintaining the mitochondrial membrane potential.
[00130] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said
10 composition is in the range of 0.06%-0.18%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential.
[00131] In an embodiment of the present disclosure, there is provided a composition comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one
15 diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, L-histidine to L-carnosine w/w ratio in said composition is 1:2, and said composition inhibits skin aging by maintaining the mitochondrial membrane potential.
20 [00132] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one
25 dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[00133] In an embodiment of the present disclosure, there is provided a composition
for use in preparing formulations, said composition comprising: (a) L-histidine; and
(b) at least one dipeptide, wherein L-histidine weight percentage in said composition
is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said
32
composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[00134] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and 5 (b) at least one dipeptide, wherein L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [00135] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and
10 (b) at least one dipeptide, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
15 [00136] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and
20 L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[00137] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and (b) at least one dipeptide, wherein the at least one dipeptide is L-carnosine, L-histidine
25 weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [00138] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and
(b) at least one dipeptide, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. 5 [00139] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition
10 is in the range of 1:2-2:1.
[00140] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the
15 range of 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2.
[00141] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; and (b) L-carnosine, wherein L-histidine weight percentage in said composition is 0.05%,
20 L-carnosine weight percentage in said composition is 0.1%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2.
[00142] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one
25 excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[00143] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 5 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
[00144] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) at
10 least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [00145] In an embodiment of the present disclosure, there is provided a composition
15 for use in preparing formulations, said composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is selected from a group consisting of L-carnosine, carnitine, and dipeptide-2, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight
20 percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1. [00146] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one
25 excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is in the range of 1:2-2:1.
[00147] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) at least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight 5 percentage in said composition is in the range of 0.03%-0.09%, the at least one dipeptide weight percentage in said composition is in the range of 0.06%-0.18%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2. [00148] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) at
10 least one dipeptide; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the at least one dipeptide is L-carnosine, L-histidine weight percentage in said composition is 0.05%, the at least one dipeptide weight percentage in said composition is 0.1%, and L-histidine to the at least one dipeptide w/w ratio in said composition is 1:2.
15 [00149] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is in the range of 0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of
20 0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is in the range of 1:2-2:1.
[00150] In an embodiment of the present disclosure, there is provided a composition for use in preparing formulations, said composition comprising: (a) L-histidine; (b) L-carnosine; (c) at least one carrier; (d) at least one diluent; and (e) at least one
25 excipient, wherein L-histidine weight percentage in said composition is in the range of
0.03%-0.09%, L-carnosine weight percentage in said composition is in the range of
0.06%-0.18%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2.
[00151] In an embodiment of the present disclosure, there is provided a composition
for use in preparing formulations, said composition comprising: (a) L-histidine; (b) L-36
carnosine; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein L-histidine weight percentage in said composition is 0.05%, L-carnosine weight percentage in said composition is 0.1%, and L-histidine to L-carnosine w/w ratio in said composition is 1:2. 5 [00152] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein said composition can be for topical application. [00153] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein said composition can be in the form of an aerosol. [00154] In an embodiment of the present disclosure, there is provided a composition
10 as described herein, wherein said composition can be in the form of a lotion.
[00155] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein said composition can be in form of an oil. [00156] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein said composition can be in the form of a serum.
15 [00157] Although the subject matter has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the subject matter, will become apparent to persons skilled in the art upon reference to the description of the subject matter. It is therefore contemplated
20 that such modifications can be made without departing from the spirit or scope of the present subject matter as defined.
EXAMPLES
[00158] The disclosure will now be illustrated with working examples, which is
25 intended to illustrate the working of disclosure and not intended to take restrictively to
imply any limitations on the scope of the present disclosure. Unless defined otherwise,
all technical and scientific terms used herein have the same meaning as commonly
understood to one of ordinary skill in the art to which this disclosure belongs.
Although methods and materials similar or equivalent to those described herein can be
37
used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may vary.
5 Example 1
Material and Methods
[00159] L-histidine (CAS No. 71-00-1) and L-carnosine (CAS no. 305-84-0) were
procured from Sigma Aldrich.
[00160] Mitochondrial Membrane Potential assay: Human adult dermal fibroblasts
10 (Himedia. India) were seeded in 96- well plates (Costar) in fibroblast growth medium (Lonza). Seeding cell density was 10000 cells per well. The culture was incubated in a 37°(7 5% CO2 incubator and was allowed to reach 75% confluency. Post 24 hrs, the medium was replenished with specific concentrations of L-histidine and L-carnosine and incubated in a 37°(75% CO2 incubator. After 24 hours, cells were subjected to
15 mitochondrial membrane potential assay using a kit procured from Sigma (catalogue no. MAK159). This kit utilizes JC-10, which is a cationic and lipophilic dye, for determining the loss of MMP (mitochondrial membrane potential membrane) in cells. JC-10 forms reversible red fluorescent aggregates (Xex=540/Xem=590nm) in mitochondria of cells with a polarized mitochondrial membrane. Whereas in apoptotic
20 cells, MMP collapse results in the failure to retain JC-10 in the mitochondria and thus the dye returns to its monomeric, green fluorescent form (Xex=490/Xem=525nm). The ratio of green to red fluorescence which is converted to percentage is used to determine MMP. A higher value of percent green to red ratio indicates lower mitochondrial membrane potential and vice versa. In this case a value of percent green
25 to red ratio greater than 100 (control) signifies disruption in MMP. All steps were
[00161] Preparation of L-histidine (H) and L-carnosine (C): Histidine was prepared in distilled water (1.55% w/v) and L- Carnosine was prepared in distilled water (2.26% w/v)
Example 2
5 Effect of combination of L-histidine and L-carnosine on mitochondrial
membrane potential
[00162] L-histidine (H) and L-carnosine (C) were tested individually and in
combination at different concentrations to determine the effect on mitochondrial
membrane potential (Figure.1, Figure.2 and Figure.3). The protocol followed for the
10 experiment was the same as mentioned in Example 1. The concentrations tested are
mentioned in the table below:
[00163] When varying concentrations of L-histidine were tested individually no decrease or marginal decrease (in case of 0.05%) in the percent green/red fluorescence ratio with respect to control was observed. Similarly, in the case of L-carnosine no decrease in the percent green/red ratio with respect to control was observed. However, 5 a remarkable decrease of almost 20% (Figure.1) was observed when the actives were tested in a combination of L-histidine 0.05% and L-carnosine 0.1%. Other combinations of actives such as H+C-0.1%+0.2% (Figure.2) and H+C-0.025%+0.05% (Figure.3) were also tested but neither showed a decrease in the percentage green/red ratio with respect to control. Thus, L-histidine and L-carnosine show distinct synergy
10 at the concentrations of 0.05% L-histidine and 0.1% L-carnosine, in combination.
[00164] Additionally, the synergistic effect of L-histidine and L-carnosine in maintaining the MMP is apparent only at the 0.05% and 0.1% (1:2 w/w ratio) weight percentages. Other combinations of the actives with different weight percentages but same ratio of 1:2 did not show any synergism. Thus, a mere admixture of the two
15 actives does not result in a decrease of percent green to red fluorescent ratio and further in the synergistic protection of MMP. Therefore, this combination of L-histidine and L-carnosine cannot be arrived at without undue experimentation.
[00165] Thus, the present disclosure provides a synergistic composition of L-histidine 20 and L-carnosine, which exhibits a synergistic protection of mitochondrial membrane potential at a weight percentage of 0.05% L-histidine and 0.1% L-carnosine. This combination can thus aid in the inhibition of skin aging process. This apparent synergism of the said combination is not readily apparent at all concentration combinations (as discussed previously), suggesting that the results are not a result of
mere admixture of the two or routine in nature. Further, the identification of this combination to reduce skin again cannot be arrived at without undue experimentation, and is not obvious to a person skilled in the art.
| # | Name | Date |
|---|---|---|
| 1 | 201741011251-RELEVANT DOCUMENTS [29-09-2023(online)].pdf | 2023-09-29 |
| 1 | Form 5 [29-03-2017(online)].pdf | 2017-03-29 |
| 2 | Form 3 [29-03-2017(online)].pdf | 2017-03-29 |
| 2 | 201741011251-IntimationOfGrant02-12-2021.pdf | 2021-12-02 |
| 3 | Drawing [29-03-2017(online)].pdf | 2017-03-29 |
| 3 | 201741011251-PatentCertificate02-12-2021.pdf | 2021-12-02 |
| 4 | 201741011251-FER_SER_REPLY [26-11-2021(online)].pdf | 2021-11-26 |
| 4 | Description(Complete) [29-03-2017(online)].pdf_173.pdf | 2017-03-29 |
| 5 | Description(Complete) [29-03-2017(online)].pdf | 2017-03-29 |
| 5 | 201741011251-FER.pdf | 2021-10-17 |
| 6 | Other Patent Document [15-05-2017(online)].pdf | 2017-05-15 |
| 6 | 201741011251-FORM 18 [24-03-2021(online)].pdf | 2021-03-24 |
| 7 | Form 26 [15-05-2017(online)].pdf | 2017-05-15 |
| 7 | Correspondence by Agent_Submission of Power of Attorney_18-05-2017.pdf | 2017-05-18 |
| 8 | Form 26 [15-05-2017(online)].pdf | 2017-05-15 |
| 8 | Correspondence by Agent_Submission of Power of Attorney_18-05-2017.pdf | 2017-05-18 |
| 9 | Other Patent Document [15-05-2017(online)].pdf | 2017-05-15 |
| 9 | 201741011251-FORM 18 [24-03-2021(online)].pdf | 2021-03-24 |
| 10 | 201741011251-FER.pdf | 2021-10-17 |
| 10 | Description(Complete) [29-03-2017(online)].pdf | 2017-03-29 |
| 11 | 201741011251-FER_SER_REPLY [26-11-2021(online)].pdf | 2021-11-26 |
| 11 | Description(Complete) [29-03-2017(online)].pdf_173.pdf | 2017-03-29 |
| 12 | Drawing [29-03-2017(online)].pdf | 2017-03-29 |
| 12 | 201741011251-PatentCertificate02-12-2021.pdf | 2021-12-02 |
| 13 | Form 3 [29-03-2017(online)].pdf | 2017-03-29 |
| 13 | 201741011251-IntimationOfGrant02-12-2021.pdf | 2021-12-02 |
| 14 | Form 5 [29-03-2017(online)].pdf | 2017-03-29 |
| 14 | 201741011251-RELEVANT DOCUMENTS [29-09-2023(online)].pdf | 2023-09-29 |
| 1 | 201741011251searchqueryE_31-03-2021.pdf |