Pharmaceutical composition for treating vitiligo

Abstract

A pharmaceutical composition for treating vitiligo comprising adenosine, 2-deoxy-D- ribose, L-arginine, and niacin. The pharmaceutical composition comprises adenosine, 2-deoxy-D- ribose, L-arginine, and niacin with a weight ratio (adenosine: 2-deoxy-D-ribose: arginine: niacin) of 1-5:1-5:1-5:1-5 in an aqueous medium. The pharmaceutical composition further comprises a solvent, a first emulsifier, a second emulsifier, an anti-oxidant, a preservative, a chelating agent, and a buffer.

Description

Ref- 1403009PHARMACEUTICAL COMPOSITION FOR TREATING VITILIGOTECHNICAL FIELD

[0001] The present disclosure generally relates to an exemplary pharmaceutical composition for treating depigmentation, and more particularly to an exemplary pharmaceutical composition for treating vitiligo.BACKGROUND

[0002] Vitiligo is an autoimmune disorder characterized by the loss of pigmentation in the skin, resulting in the formation of lighter patches. This condition can adversely affect an individual’s appearance and contribute to a decrease in self-esteem, as it is a consequence of the immune system’s attack on melanocytes. Epidemiological data indicate that vitiligo affects approximately 0.5 to 1% of the global population, with a range of factors — such as genetic background, immune response, and stress levels — potentially influencing the likelihood of its development.

[0003] Examining the molecular mechanisms associated with vitiligo reveals that elevated levels of reactive oxygen species (ROS) can lead to melanocyte dysfunction and subsequent cell death. Numerous factors, including ultraviolet (UV) radiation, psychological stress, and exposure to chemical agents, are known to contribute to increased ROS levels. Therefore, medical interventions aimed at mitigating ROS levels in the depigmented skin patches may enhance melanocyte survival and promote the reduction of lesions. One promising approach to decreasing ROS levels in affected skin areas is the enhancement of blood circulation, which may supply essential nutrients and wash out ROS and excessive inflammation moieties, supporting melanocyte viability against immune system attacks. Consequently, natural ingredients that improve blood circulation could be effective in alleviating the symptoms of vitiligo.Ref- 1403009

[0004] Thereby there is a significant need for the development of a pharmaceutical composition composed of natural ingredients that can enhance blood circulation, targeting the fundamental molecular mechanisms implicated in vitiligo, thereby providing a viable therapeutic strategy for the management of this condition.SUMMARY

[0005] This summary is intended to provide an overview of the subject matter of the present disclosure, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. Its sole purpose is to present some concepts of one or more exemplary aspects in a simplified form as a prelude to the more detailed description that is presented later. The proper scope of the present disclosure may be ascertained from the claims set forth below in view of the detailed description below and the drawings.

[0006] One or more exemplary embodiments describe an exemplary pharmaceutical composition for treating vitiligo. Exemplary pharmaceutical composition may comprise adenosine, 2-deoxy-D-ribose, L-arginine, and niacin. Exemplary pharmaceutical composition may comprise adenosine, 2-deoxy-D-ribose, L-arginine, and niacin with a weight ratio (adenosine: 2-deoxy-D-ribose: arginine: niacin) of 1-5: 1-5: 1-5: 1-5 in an exemplary aqueous medium. Exemplary pharmaceutical composition may comprise adenosine with a concentration between 0.1% (w / v) and 10% (w / v). Exemplary pharmaceutical composition may comprise 2-deoxy-D-ribose with a concentration between 0.1% (w / v) and 10% (w / v). Exemplary pharmaceutical composition may comprise L-arginine with a concentration between 0.1% (w / v) and 10% (w / v). Exemplary pharmaceutical composition may comprise niacin with a concentration between 0.1% (w / v) and 10% (w / v).

[0007] Exemplary pharmaceutical composition may further comprise an exemplary solvent, an exemplary first emulsifier, an exemplary second emulsifier, an exemplary anti-oxidant, anRef- 1403009exemplary preservative, an exemplary chelating agent, and an exemplary buffer. An exemplary solvent may be propylene glycol. An exemplary first emulsifier may be octoxynol-9. An exemplary second emulsifier may be sorbitan stearate. An exemplary anti-oxidant may be vitamin E. An exemplary preservative may be 2-phenoxyethanol. An exemplary chelating agent may be ethylenediamine tetra acetic acid. An exemplary buffer may be sodium acetate trihydrate.

[0008] An exemplary topical pharmaceutical composition for treating vitiligo may comprise adenosine with a concentration between 0.1% (w / v) and 10% (w / v), 2-deoxy-D-ribose with a concentration between 0.1% (w / v) and 10% (w / v), L-arginine with a concentration between 0.1% (w / v) and 10% (w / v), niacin with a concentration between 0.1% (w / v) and 10% (w / v), propylene glycol with a concentration between 3% (w / v) and 7% (w / v), octoxynol-9 with a concentration between 0.1% (w / v) and 0.3% (w / v), sorbitan stearate with a concentration between 0.3% (w / v) and 0.7% (w / v), vitamin E with a concentration between 0.1% (w / v) and 0.3% (w / v), 2-phenoxyethanol with a concentration between 0.6% (w / v) and 0.8% (w / v), ethylenediamine tetra acetic acid with a concentration between 0.1% (w / v) and 0.3% (w / v), sodium acetate trihydrate with a concentration between 0.1% (w / v) and 0.3% (w / v) in an exemplary aqueous medium.

[0009] This Summary may introduce a number of concepts in a simplified format; the concepts are further disclosed within the “Detailed Description” section. This Summary is not intended to configure essential / key features of the claimed subject matter, nor is intended to limit the scope of the claimed subject matter.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The novel features which are believed to be characteristic of the present disclosure, as to its structure, organization, use and method of operation, together with further objectives and advantages thereof, will be better understood from the following drawings in which an exemplary embodiment will now be illustrated by way of example. It is expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as aRef- 1403009definition of the limits of the present disclosure. Exemplary embodiments will now be described by way of example in association with the accompanying drawings in which:

[0011] FIG. 1 illustrates a flowchart of an exemplary method for synthesis of an exemplary pharmaceutical composition, consistent with one or more exemplary embodiments of the present disclosure.

[0012] FIG. 2 illustrates a bar chart of fluorescent dye 2'7'-dichlorofluorescein diacetate (DCFH-DA) signal in human epidermal melanocyte cells following treatment with exemplary active ingredients of an exemplary pharmaceutical composition in a separate scenario and a mixture of exemplary active ingredients, consistent with one or more exemplary embodiments of the present disclosure.

[0013] FIG. 3 illustrates images of negative control, positive control and test group mice, consistent with one or more exemplary embodiments of the present disclosure.

[0014] FIG. 4 illustrates a bar chart representing transcutaneous oxygen pressure (mmHg) in negative control and test group mice, consistent with one or more exemplary embodiments of the present disclosure.DETAILED DESCRIPTION

[0015] detailed description, numerous specific details are set forth by way of examples to provide a thorough understanding of the relevant teachings related to the exemplary embodiments. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well-known methods, procedures, components, and / or circuitry have been described at a relatively high level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0016] The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in one or more exemplary embodiments of the present disclosure. For purposes of explanation, specific nomenclature is set forth to provide aRef- 1403009thorough understanding of the present disclosure. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to the exemplary implementations will be plain to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from the scope of the present disclosure. The present disclosure is not intended to be limited to the implementations shown but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0017] Disclosed herein is an exemplary pharmaceutical composition for treating vitiligo. ‘Vitiligo’ may refer to a chronic autoimmune disorder characterized by depigmented patches of skin. In an exemplary embodiment, molecular mechanism of vitiligo is rooted in melanocytes that may be attacked and destroyed by antigen- specific T cells, which may result in patchy depigmentation. In an exemplary embodiment, common drugs used to treat vitiligo may be ineffective, carry a significant risk of adverse effects (such as increased risk of skin sensitivity, skin cancer, and infection), or be unsuitable for young patients. More importantly, common drugs often focus on managing symptoms rather than addressing the underlying molecular mechanism, leading to limited success.

[0018] In an exemplary embodiment, an exemplary pharmaceutical composition may comprise adenosine, 2-deoxy-D-ribose, L-arginine, and niacin as exemplary active ingredients. In an exemplary embodiment, adenosine, 2-deoxy-D-ribose, L-arginine, and niacin may enhance blood circulation in skin patches. In an exemplary embodiment, adenosine, 2-deoxy-D-ribose, arginine, and niacin may lead to a more rapid removal of ROS and excessive inflammation moieties from vitiligo lesions. In an exemplary embodiment, enhancement in blood circulation may lead to supplementing essential nutrients for melanocytes, thus surviving from immune system attack. In an exemplary embodiment, improved blood circulation may help alleviate symptoms in patients with immune -related skin conditions like vitiligo, alopecia areata andRef- 1403009psoriasis. An exemplary embodiment, an exemplary pharmaceutical composition may comprise adenosine, 2-deoxy-D-ribose, L-arginine, and niacin with a weight ratio (adenosine: 2-deoxy-D-ribose: L-arginine: niacin) of 1-5: 1-5: 1-5: 1-5 in an exemplary aqueous medium. In an exemplary embodiment, an exemplary pharmaceutical composition may comprise adenosine with a concentration between 0.1% (w / v) and 10% (w / v). In an exemplary embodiment, an exemplary pharmaceutical composition may comprise 2-deoxy-D-ribose with a concentration between 0.1% (w / v) and 10% (w / v). In an exemplary embodiment, an exemplary pharmaceutical composition may comprise L-arginine with a concentration between 0.1% (w / v) and 10% (w / v). In an exemplary embodiment, an exemplary pharmaceutical composition may comprise niacin with a concentration between 0.1% (w / v) and 10% (w / v).

[0019] In an exemplary embodiment, an exemplary pharmaceutical composition may further comprise an exemplary solvent, an exemplary first emulsifier, an exemplary second emulsifier, an exemplary anti-oxidant, an exemplary preservative, an exemplary chelating agent, and an exemplary buffer.

[0020] In an exemplary embodiment, an exemplary solvent may be propylene glycol. In an exemplary embodiment, an exemplary first emulsifier may be octoxynol-9. In an exemplary embodiment, an exemplary second emulsifier may be sorbitan stearate. In an exemplary embodiment, an exemplary ant-oxidant may be vitamin E. In an exemplary embodiment, an exemplary preservative may be 2 -phenoxyethanol. In an exemplary embodiment, an exemplary chelating agent may be ethylenediamine tetra acetic acid. In an exemplary embodiment, an exemplary buffer may be sodium acetate trihydrate.

[0021] In an exemplary embodiment, an exemplary topical pharmaceutical composition for treating vitiligo may comprise adenosine with a concentration between 0.1% (w / v) and 10% (w / v), 2-deoxy-D-ribose with a concentration between 0.1% (w / v) and 10% (w / v), L-arginine with a concentration between 0.1% (w / v) and 10% (w / v), niacin with a concentration between 0.1% (w / v) and 10% (w / v), propylene glycol with a concentration between 3% (w / v) and 7% (w / v), octoxynol-Ref- 14030099 with a concentration between 0.1% (w / v) and 0.3% (w / v), sorbitan stearate with a concentration between 0.3% (w / v) and 0.7% (w / v), vitamin E with a concentration between 0.1% (w / v) and 0.3% (w / v), 2-phenoxyethanol with a concentration between 0.6% (w / v) and 0.8% (w / v), ethylenediamine tetra acetic acid with a concentration between 0.1% (w / v) and 0.3% (w / v), and sodium acetate trihydrate with a concentration between 0.1% (w / v) and 0.3% (w / v) in an exemplary aqueous medium.

[0022] FIG. 1 illustrates a flowchart 100 of an exemplary method for synthesis of an exemplary pharmaceutical composition, consistent with one or more exemplary embodiments of the present disclosure. In one or more exemplary embodiments, exemplary method 100 may comprise: forming an exemplary first phase by mixing propylene glycol, octoxynol-9, sorbitan stearate and vitamin E (step 102); forming an exemplary second phase by dissolving 2-phenoxyethanol, ethylenediamine tetra acetic acid, sodium acetate, adenosine, 2-deoxy-D-ribose, L-arginine and niacin in distilled water (step 104); and forming an exemplary pharmaceutical composition by adding an exemplary first phase to an exemplary second phase (step 106).

[0023] In further detail with respect to step 102, step 102 may comprise forming an exemplary first phase by mixing propylene glycol, octoxynol-9, sorbitan stearate and vitamin E. In an exemplary embodiment, forming an exemplary first phase by mixing propylene glycol, octoxynol-9, sorbitan stearate and vitamin E may include mixing propylene glycol, octoxynol-9 and sorbitan stearate in a weight ratio (propylene glycol: octoxynol-9: sorbitan stearate) of 50:2:5, followed by heating up to a temperature level of about 60 °C till sorbitan stearate melts to liquid form, cooling down to a temperature level of about 50 °C, and adding vitamin E with a concentration of (with respect to final volume of an exemplary first phase) about 0.2% (w / v) under continuous stirring, followed by rapidly cooling down to a temperature level of about 25 °C.

[0024] In further detail with respect to step 104, step 104 may comprise forming an exemplary second phase by dissolving 2-phenoxyethanol, ethylenediamine tetra acetic acid, sodium acetate, adenosine, 2-deoxy-D-ribose, L-arginine and niacin in distilled water. In an exemplaryRef- 1403009embodiment, forming an exemplary second phase by dissolving 2-phenoxyethanol, ethylenediamine tetra acetic acid, sodium acetate, adenosine, 2-deoxy-D-ribose, L-arginine and niacin in distilled water may include dissolving 2-phenoxyethanol with a final concentration of (with respect to the final volume of an exemplary second phase) of about 0.8% (w / v), ethylenediamine tetra acetic acid (EDTA) with a final concentration of (with respect to the final volume of an exemplary second phase) of about 0.2% (w / v), and sodium acetate trihydrate with a final concentration (with respect to the final volume of an exemplary second phase) of about 0.25% in distilled water under continuous stirring at a temperature level of about 25 °C, followed by pH adjustment at 5.0+0.1 by adding acetic acid glacial, and dissolving adenosine with a concentration of about 5 g / L, 2-deoxy-D-ribose with a concentration of about 5 g / L, L-arginine with a concentration of about 5 g / L and niacin with a concentration of about 5 g / L.

[0025] In further detail with respect to step 106, step 106 may comprise forming an exemplary pharmaceutical composition by adding an exemplary first phase to an exemplary second phase. In an exemplary embodiment, forming an exemplary pharmaceutical composition by adding an exemplary first phase to an exemplary second phase may include adding an exemplary first phase to an exemplary second phase under continuous stirring at a temperature level of about 25 °C. EXAMPLES

[0026] Hereinafter, one or more exemplary embodiments will be described in further detail with reference to examples. It will be obvious to a person having ordinary skill in the art that these examples may be for illustrative purposes only and are not to be interpreted to limit the scope of the present disclosure.Example 1: A Method for Synthesis of Pharmaceutical Composition

[0027] In this example, exemplary pharmaceutical composition was synthesized based on an exemplary process similar to method 100. To synthesize exemplary pharmaceutical composition, firstly an exemplary first phase may be prepared in a first solution container. An exemplaryRef- 1403009container may include but is not limited to, beakers, tins, flasks, tanks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, in first step an exemplary first mixture may be prepared by mixing propylene glycol, octoxynol-9 and sorbitan stearate in a weight ratio (propylene glycol: octoxynol-9: sorbitan stearate) of 50:2:5, followed by heating up to a temperature level of about 60 °C till sorbitan stearate melts to liquid form and then cooling down to a temperature level of about 50 °C. In the next step, vitamin E is added to an exemplary first mixture with a final concentration of (with respect to the final volume of an exemplary first phase) of about 0.2% (w / v) under continuous stirring, followed by rapidly cooling down to a temperature level of about 25 °C, resulting in formation of an exemplary first phase.

[0028] For example, to prepare about 60 mL of an exemplary first phase, 50 g of propylene glycol, 2 g of octoxynol-9 and 5 g of sorbitan stearate may be mixed and then heated up to a temperature level of about 60 °C till sorbitan stearate melts to liquid form and then cooling down to a temperature level of about 50 °C. In the next step, 2 g of vitamin E is added to an exemplary first mixture under continuous stirring, followed by rapidly cooling down to a temperature level of about 25 °C, resulting in formation of 60 mL of an exemplary first phase.

[0029] Separately, an exemplary second phase may be prepared in a second solution container. In an exemplary embodiment, in first step, an exemplary second mixture may be prepared by dissolving 2-phenoxyethanol with a final concentration of (with respect to the final volume of an exemplary second mixture) of about 0.8% (w / v), ethylenediamine tetra acetic acid (EDTA) with a final concentration of (with respect to the final volume of an exemplary second mixture) of about 0.2% (w / v), and sodium acetate trihydrate with a final concentration (with respect to the final volume of an exemplary second mixture) of about 0.25% in distilled water under continuous stirring at a temperature level of about 25 °C. In an exemplary embodiment, an exemplary water used for preparing an exemplary second mixture may include distilled water, double-distilled water, or ultrapure water. “Ultrapure water” may refer to water that has been purified using a combination of ultrafiltration technologies and ultraviolet photo -oxidation system.Ref- 1403009In the next step, pH of an exemplary second mixture is adjusted at 5.0+0.1 by adding acetic acid glacial, resulting in formation of an exemplary second phase.

[0030] For example, to prepare about 940 mL of an exemplary second phase, 8 g of 2-phenoxyethanol, 2 g of EDTA and 2.5 g of sodium acetate trihydrate may be dissolved in 930 mL of distilled water under continuous stirring at a temperature level of about 25 °C. In the next step, pH of an exemplary second mixture is adjusted at 5.0+0.1 by adding acetic acid glacial, resulting in formation of 940 mL of an exemplary second phase.

[0031] In the final step, an exemplary first phase is added to an exemplary second phase under continuous stirring at a temperature level of about 25 °C, resulting in formation of an exemplary pharmaceutical composition. For example, to prepare 1000 mL of an exemplary pharmaceutical composition, 60 mL of an exemplary first phase may be added to 940 mL of an exemplary second phase under continuous stirring at a temperature level of about 25 °C.Example 2: In-Vitro Cytotoxicity Assessment of Pharmaceutical Composition

[0032] In this example, cytotoxicity of exemplary produced pharmaceutical composition in “Example 1” was characterized by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide” assay (MTT). In this test, the cytotoxicity of different exemplary active ingredients in an exemplary pharmaceutical composition against human epidermal melanocyte cell line was assessed. For this purpose, human epidermal melanocyte cell (5xl03) was seeded in a 96-well plate and cultured for 24 hours. After treatment with each exemplary active ingredient, 10 pL of MTT is added to each well, followed by incubation at 37 °C for 4 h. Then, 100 pL of sodium dodecyl sulfate was added to each well, followed by an overnight incubation to dissolve formazan crystal. Next day, absorbance at wavelength of 570 nm was measured using a microplate spectrophotometer. Table 1 below shows the output of MTT assay for human epidermal melanocyte cells in a 96-well plate at varying concentrations (between 10 pM and 1280 pM) of each exemplary active ingredient of an exemplary pharmaceutical composition.Ref- 1403009Table 1: absorbance values measured at wavelength of 570 nm for human epidermal melanocyte cells at varying concentrations (between 10 pM and 1280 pM) of each exemplary active ingredient of an exemplary pharmaceutical composition, consistent with one or more exemplary embodiments of the present disclosure.

[0033] Looking at Table 1, it reveals that niacin has exhibited the highest half-maximal inhibitory concentration (IC50) at 526 pM whereas adenosine has demonstrated the lowest at 75 pM. The IC50 results indicate that all exemplary active ingredients of an exemplary pharmaceutical composition are tolerated by human melanocytes at concentrations below 40 pM. Based on MTT assay results, a concentration of 40 pM for exemplary all active ingredients of an exemplary pharmaceutical composition were selected for the subsequent in vitro and in vivo experiments.Example 3: Anti-oxidant Activity of Pharmaceutical Composition

[0034] In this example, anti-oxidant activity of exemplary produced pharmaceutical composition in “Example 1” was characterized by fluorescent dye 2'7'-dichlorofluorescein diacetate (DCFH-DA). In this test, human epidermal melanocyte cells (IxlO4) were seeded and cultured in 96-well plate, followed by incubation at 37 °C for 24 hours. Then, DCFH-DA was added to each well of 96-well plate with a final concentration of 10 pM, followed by incubationRef- 1403009in the dark at 37 °C for 1 hour. After 1 hour, the medium was withdrawn and cells were subjected to H2O2, followed by adding exemplary active ingredients of an exemplary pharmaceutical composition with a final concentration of 40 pM. After that, the level of reactive oxygen species (ROS) was quantified by measuring DCF fluorescent intensity at a wavelength between 485 nm and 530 nm to understand exemplary active ingredients’ potential to remove ROS.

[0035] FIG. 2 illustrates a bar chart 200 of fluorescent dye 2 '7 '-dichloro fluorescein diacetate (DCFH-DA) signal in human epidermal melanocyte cells following treatment with exemplary active ingredients of an exemplary pharmaceutical composition in a separate scenario and a mixture of exemplary active ingredients, consistent with one or more exemplary embodiments of the present disclosure. Referring to the FIG. 2, ROS level in H2O2-treated melanocyte cells is significantly higher than untreated group (control). Niacin and adenosine have demonstrated greater efficiency in reducing ROS levels compared to 2-deoxy-D-ribose, while L-arginine falls in between. Cells treated with the mixture of exemplary active ingredients of an exemplary pharmaceutical composition exhibited the lowest level of ROS, compared to each exemplary active ingredient of an exemplary pharmaceutical composition.Example 4: Animal Experiment of Pharmaceutical Composition

[0036] In this example, animal experiment of exemplary produced pharmaceutical composition in “Example 2” was conducted on chemical-induced animal model. To conduct the experiment, mice were divided into 3 groups, each consisting of 7 mice. The groups included a negative control group which was treated exclusively with distilled water for two weeks, a positive control group received a topical application of 60% monobenzone cream for two weeks to induce vitiligo, and a test group which was also treated with 60% monobenzone cream for two weeks, followed by the application of an emulsion containing each exemplary active ingredient of an exemplary pharmaceutical composition or their mixture at a concentration of 5 g / L.

[0037] For the experimental procedure, the hair of dorsal skin was shaved over in a 3x2 cm2area. During the initial first two weeks, distilled water was administered to negative control group,Ref- 1403009while 60% monobenzone cream was applied on skin of both positive control and test groups to chemically induce vitiligo. Subsequently, for an additional two weeks, an emulsion of each exemplary active ingredient of an exemplary pharmaceutical composition or their mixture at a concentration of 5 g / L was applied to the skin of mice in test group. Photographic documentation of each group of mice was conducted to monitor changes in pigmentation.

[0038] FIG. 3 illustrates images 300 of negative control, positive control and test group mice, consistent with one or more exemplary embodiments of the present disclosure. As depicted in FIG.3, topical application of 60% monobenzone cream resulted in induction of vitiligo in control positive and test group after 14 days, as evidenced by degradation of melanocyte and melanosome. Conversely, control negative group 302 treated solely with topical application of distilled water did not exhibit any sign of vitiligo.

[0039] By day 28 of experiment, positive control group continued to display pronounced skin and hair depigmentation, as they did not receive any therapeutic intervention to counteract vitiligo. In contrast, all mice receiving emulsion of each exemplary active ingredient of an exemplary pharmaceutical composition or their mixture demonstrated a gradual darkening in both skin and hair, indicating the efficiency of these exemplary active ingredients in combating vitiligo. Among the test group on day 28, mice treated with 2-deoxy-D-ribose showed more significant improvement compared to other exemplary active ingredients of an exemplary pharmaceutical composition. Notably, the mixture of all exemplary active ingredients of an exemplary pharmaceutical composition yielded the most pronounced repigmentation among other treatments.

[0040] Radiometer TCM400 is a non-invasive transcutaneous monitoring device to measure transcutaneous oxygen tension (tcpCh). tcpCh measures the amount of oxygen that diffuses from the capillary through the epidermis to the electrode and thus provides information on the amount of oxygen delivered to the skin through blood circulation. Therefore, tcpO2 measurement is an indicator of changes in the skin’s blood circulation which can be used to understand if exemplaryRef- 1403009active ingredients of an exemplary pharmaceutical composition might help to combat vitiligo through improvement in skin’s blood circulation.

[0041] FIG. 4 illustrates a bar chart 400 representing transcutaneous oxygen pressure (mmHg) in negative control and test group mice, consistent with one or more exemplary embodiments of the present disclosure. As shown in FIG. 4, transcutaneous partial pressure of oxygen was highest in mice treated with 2-deoxy-D-ribose, indicating a higher level of cutaneous blood circulation in this group. Other mice in test group receiving adenosine, L-arginine and niacin showed a modest increase in tcpO2 compared to negative control group. Mice treated with emulsion containing all exemplary active ingredients of an exemplary pharmaceutical composition showed the highest level of improvement in cutaneous blood circulation, 16% higher than those treated with 2-deoxy-D-ribose.

[0042] While the foregoing has described what are considered to be the best mode and / or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.

[0043] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0044] The scope of protection is limited solely by the claims that now follow. That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy theRef- 1403009requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way. Any unintended embracement of such subject matter is hereby disclaimed.

[0045] Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.

[0046] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein. Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions. An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0047] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0048] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study, except where specific meanings have otherwise been set forth herein. Relational terms such as “first” and “second” and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions.

[0049] The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used toRef- 1403009interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it may be seen that various features are grouped together in various implementations. This is for purposes of streamlining the disclosure, and is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter.

[0050] While various implementations have been described, the description is intended to be exemplary, rather than limiting and it will be apparent to those of ordinary skill in the art that many more implementations and implementations are possible that are within the scope of the implementations. Although many possible combinations of features are shown in the accompanying figures and discussed in this detailed description, many other combinations of the disclosed features are possible. Any feature of any implementation may be used in combination with or substituted for any other feature or element in any other implementation unless specifically restricted. Therefore, it will be understood that any of the features shown and / or discussed in the present disclosure may be implemented together in any suitable combination. Accordingly, the implementations are not to be restricted except in light of the attached claims and their equivalents. Also, various modifications and changes may be made within the scope of the attached claims.

Claims

Ref- 1403009What is claimed is:

1. A pharmaceutical composition for treating vitiligo comprising adenosine, 2-deoxy-D-ribose, L-arginine, and niacin.

2. The pharmaceutical composition of claim 1, comprising adenosine, 2-deoxy-D-ribose, L-arginine, and niacin with a weight ratio (adenosine: 2-deoxy-D-ribose: arginine: niacin) of 1-5:1-5: 1-5: 1-5 in an aqueous medium.

3. The pharmaceutical composition of claim 1, wherein adenosine has a concentration between 0.1% (w / v) and 10% (w / v).

4. The pharmaceutical composition of claim 1, wherein 2-deoxy-D-ribose has a concentration between 0.1% (w / v) and 10% (w / v).

5. The pharmaceutical composition of claim 1, wherein L-arginine has a concentration between 0.1% (w / v) and 10% (w / v).

6. The pharmaceutical composition of claim 1, wherein niacin has a concentration between 0.1% (w / v) and 10% (w / v).

7. The pharmaceutical composition of claim 1, further comprising a solvent, a first emulsifier, a second emulsifier, an anti-oxidant, a preservative, a chelating agent, and a buffer.

8. The pharmaceutical composition of claim 7, wherein the solvent is propylene glycol.

9. The pharmaceutical composition of claim 7, wherein the first emulsifier is octoxynol-9.

10. The pharmaceutical composition of claim 7, wherein the second emulsifier is sorbitan stearate.

11. The pharmaceutical composition of claim 7, wherein the anti-oxidant is vitamin E.

12. The pharmaceutical composition of claim 7, wherein the preservative is 2-phenoxyethanol.

13. The pharmaceutical composition of claim 7, wherein the chelating agent is ethylenediamine tetra acetic acid.

14. The pharmaceutical composition of claim 7, wherein the buffer is sodium acetate trihydrate.

15. A topical pharmaceutical composition for treating vitiligo, comprising:Ref- 1403009adenosine with a concentration between 0.1% (w / v) and 10% (w / v), 2-deoxy-D-ribose with a concentration between 0.1% (w / v) and 10% (w / v), L-arginine with a concentration between 0.1% (w / v) and 10% (w / v), niacin with a concentration between 0.1% (w / v) and 10% (w / v), propylene glycol with a concentration between 3% (w / v) and 7% (w / v), octoxynol-9 with a concentration between 0.1% (w / v) and 0.3% (w / v), sorbitan stearate with a concentration between 0.3% (w / v) and 0.7% (w / v), vitamin E with a concentration between 0.1% (w / v) and 0.3% (w / v), 2-phenoxyethanol with a concentration between 0.6% (w / v) and 0.8% (w / v), ethylenediamine tetra acetic acid with a concentration between 0.1% (w / v) and 0.3% (w / v), and sodium acetate trihydrate with a concentration between 0.1% (w / v) and 0.3% (w / v) in an aqueous medium.

Images