Skin Care and Treatments of Melbourne Dermatology - Myristyl Nicotinate

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Myristyl Nicotinate

Myristyl Nicotinate

Myristyl nicotinate is a substance being studied in the prevention of skin cancer.

Myristyl nicotinate cream is also being studied as a way to help lessen the side effects of retinoic acid (a form of vitamin A) when it is used to treat skin that has been damaged by the sun.

Myristyl nicotinate cream contains a form of niacin (a member of the vitamin B complex).

Myristyl nicotinate is a type of chemopreventive (photoprotective) agent.

Wednesday, 28 July 2010

Topical Myristyl Nicotinate Creams

Topical Myristyl Nicotinate Creams

Nia 24 contains the ester prodrug myristyl nicotinate (MN), a lipophilic nicotinic acid derivative with potential chemopreventive activity.

Upon topical application, myristyl nicotinate penetrates into the epidermis where the agent is cleaved and is converted into nicotinic acid (also known as niacin and nicotinamide).

Nicotinic acid then diffuses into cells where it is converted to nicotinamide adenine dinucleotide (NAD).

NAD may stimulate poly(ADP-ribose) polymerase-1 (PARP-1), enhance skin cell turnover and epidermal differentiation and strengthen skin barrier function.

NAD is a coenzyme that plays a crucial role in many redox reactions.

PARP-1 is an enzyme that plays an important role in DNA repair.

Sunday, 9 August 2009

Formulation Compatibility of Myristyl Nicotinate with Drugs Used to Treat Dermatological Conditions Involving an Impaired Skin Barrier

A number of dermatology conditions including skin photodamage, atopic dermatitis, and rosacea involve skin barrier impairment and first line therapies for these conditions including retinoids and steroids further impair skin barrier function.

We have evaluated the compatibility of myristyl nicotinate, an agent that enhances skin barrier function, with drugs used to treat conditions where skin barrier impairment is present including photodamage (retinoic acid), atopic dermatitis (hydrocortisone, triamcinolone acetonide), rosacea (metronidazole), and seborrheic dermatitis (ketoconazole).

Myristyl nicotinate was found to be compatible with each of the drugs examined when formulated together and also was shown to be photocompatible with retinoic acid.

Our results suggest that the combination of myristyl nicotinate with these drugs is a feasible therapeutic development strategy.

Drug development and industrial pharmacy.

2007, vol. 33, no11, pp. 1176-1182 [7 page(s) (article)] (1/4 p.)

Wednesday, 28 July 2010

Study: Topical Myristyl Nicotinate Cream on the Skin of Healthy Volunteers

University of Arizona

National Cancer Institute (NCI)

ClinicalTrials.gov Identifier: NCT00619060


Chemoprevention is the use of certain drugs to keep cancer from forming.

The use of topical myristyl nicotinate cream may stop skin cancer from forming.

This randomized phase I trial is studying the side effects and best way to give topical myristyl nicotinate cream on the skin of healthy volunteers.

Study placed in the following topic categories:

Antimetabolites

Vasodilator Agents

Niacinamide

Vitamin B Complex

Skin Diseases

Antilipemic Agents

Trace Elements

Healthy

Cardiovascular Agents

Skin Neoplasms

Nicotinamide

Nicotinic Acids

Vitamin B3

Vitamins

Micronutrients

Nicotinic Acid

Niacin

Wednesday, 14 October 2009

Effect of Myristyl Nicotinate on Retinoic Acid Therapy for Facial Photodamage

Based on the hypothesis that skin barrier impairment is a contributor to side-effects associated with retinoic acid therapy, a double-blind, placebo-controlled pilot study examined the combined use of retinoic acid with myristyl nicotinate (MN), a lipophilic derivative of niacin that enhances skin barrier function, in female subjects with mild to moderate facial photodamage.

The study involved a 1-month run-in period with placebo or MN prior to initiation of retinoic acid therapy for 3 months. Analysis of skin biopsies revealed that retinoic acid therapy resulted in stratum corneum thinning of approximately 25% (P = 0.006 versus baseline) that was ameliorated by myristyl nicotinate use (P < 0.005).

Therapy resulted in an increased rate of transepidermal water loss (TEWL) of approximately 45% (P = 0.001 versus baseline) and use of myristyl nicotinate protected against the increase in TEWL with the strongest protection provided by prior use of myristyl nicotinate (P = 0.056 versus placebo).

Myristyl nicotinate use reduced the incidence of side-effects of the therapy and again prior use provided the greatest reduction of side-effects.

Subjects showed statistically significant clinical improvement (P < 0.05 versus baseline) during the study.

Myristyl nicotinate use did not interfere with any clinical improvement parameters and improved effects on temple laxity (P = 0.01 versus placebo).

Analysis of changes in epidermal thickness, Ki67-positive cells and intensity of loricrin staining demonstrated that MN either improved or did not interfere with retinoic acid efficacy.

These results show that prior and concurrent use of myristyl nicotinate can mitigate barrier impairment and improve the tolerability of retinoic acid therapy for facial photodamage without interfering with efficacy.

Department of Pharmacology & Toxicology, College of Pharmacy, and Arizona Cancer Center, University of Arizona, Niadyne Development Inc.,Tucson, AZ 85724, USA. mjacobson@pharmacy.arizona.edu

Jacobson MK, Kim H, Coyle WR, Kim M, Coyle DL, Rizer RL, Jacobson EL.

Wednesday, 28 July 2010

A Topical Lipophilic Niacin Derivative Increases NAD, Epidermal Differentiation and Barrier Function in Photodamaged Skin

The effects of myristyl nicotinate (MN), a nicotinic acid derivative designed to deliver nicotinic acid to skin without vasodilatation, on subjects with photodamaged skin have been studied.

Myristyl nicotinate increased skin cell nicotinamide adenine dinucleotide (NAD) by 25% (P = 0.001) demonstrating effective delivery of nicotinic acid to skin.

Relative to placebo, myristyl nicotinate treatment of photodamaged facial skin increased stratum corneum thickness by approximately 70% (P = 0.0001) and increased epidermal thickness by approximately 20% (P = 0.001).

In two separate studies, myristyl nicotinate treatment increased rates of epidermal renewal by 6% (P = 0.003) to 11% (P = 0.001) and increased the minimal erythemal dose by 8.9 (P = 0.07) and 10% (P = 0.05) relative to placebo. M

Myristyl nicotinate treatment resulted in reductions in the rates of transepidermal water loss (TEWL) of approximately 20% relative to placebo on cheeks (P = 0.012) and arms (P = 0.017) of study subjects.

Results of a tape stripping challenge before and after myristyl nicotinate treatment demonstrated a significant correlation (P = 0.03) between increased skin NAD content and resistance to changes in TEWL for myristyl nicotinate treated but not placebo subjects.

Rates of TEWL changed more rapidly and to a greater extent in atopic subjects compared with normal subjects.

The results indicate that myristyl nicotinate enhances epidermal differentiation and barrier function in skin, suggesting that this method of nicotinic acid delivery may prove useful in limiting progression of actinic skin damage and possibly in treating other conditions involving skin barrier impairment.

Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85724, USA. elaine.jacobson@pharmacy.arizona.edu

Jacobson EL, Kim H, Kim M, Williams JD, Coyle DL, Coyle WR, Grove G, Rizer RL, Stratton MS, Jacobson MK.

Thursday, 21 May 2009

Analysis and Stability Study of Myristyl Nicotinate in Dermatological Preparations by High-Performance Liquid Chromatography

Myristyl nicotinate is an ester prodrug under development for delivery of nicotinic acid to skin for treatment and prevention of conditions that involve skin barrier impairment such as chronic photodamage and atopic dermatitis or for mitigating skin barrier impairment that results from therapy such as retinoids or steroids.

The formulation stability of myristyl nicotinate is crucial because even small amounts of free nicotinic acid cause skin flushing, an effect that is not harmful but would severely limit tolerability.

We report here reversed-phase HPLC methods for the rapid analysis of myristyl nicotinate and nicotinic acid in dermatological preparations [see NIA 24].

Because of the large differences in polarity, myristyl nicotinate and nicotinic acid were analyzed by different chromatographic conditions, but they can be rapidly extracted from cream formulations using HPLC mobile phase as a solvent followed by HPLC analysis in less than 10 min.

The methods were validated in terms of linearity, precision and accuracy and mean recovery of myristyl nicotinate from topical creams ranged from 97.0-101.2%. Nicotinic acid at levels of 0.01% in the formulations could be quantified.

Stability studies show that myristyl nicotinate formulations are stable at room temperature for 3 years with less than 0.05% conversion to nicotinic acid. These methods will be effective for routine analysis of myristyl nicotinate stability in dermatological formulations [see NIA 24].

J Pharm Biomed Anal. 2007 Feb 19;43(3):893-9. Epub 2006 Oct 16.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.

Tashtoush BM, Qasem J, Williams JD, DeWald TP, Jacobson EL, Jacobson MK.

Wednesday, 28 July 2010

Simultaneous Determination of Myristyl Nicotinate, Nicotinic Acid and Nicotinamide in Rabbit Plasma by Liquid Chromatography—Tandem Mass Spectrometry Using Methyl Ethyl Ketone as a Deproteinization Solvent

Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its progression to skin cancer.

To facilitate dermal studies of Nia-114, a novel liquid chromatography—tandem mass spectrometry (LC—MS/MS) method using methyl ethyl ketone (MEK) as a deproteinization solvent was developed and validated for the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit plasma.

NAM is the principal metabolite of NIC, which is also expected to have chemopreventive properties. The analytes were chromatographically separated using a Spherisorb Cyano column under isocratic conditions, and detected by multiple reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run time of 9 min.

The method utilized a plasma sample volume of 0.2 ml and isotope-labeled D4 forms of each analyte as internal standards. The method was linear over the concentration range of 2—1000, 8—1000, and 75—1000 ng/ml, for Nia-114, NIC, and NAM, respectively.

The intra- and inter-day assay accuracy and precision were within ±15% for all analytes at low, medium, and high quality control standard levels.

The relatively high value for the lower limit of quantitation (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human, dog, rat, and mouse plasma were also determined, and mean values ranged from <2 ng/ml NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of 44—50% at room temperature by 2 h, and loss of 64—70% upon storage at ?20 °C for 1 week, whereas it was stable (<7% loss) upon storage at ?80 °C for 1 month.

Journal of Chromatography.

Volume 829, Issues 1-2, 27 December 2005, Pages 123-135

Paul Catza, Walter Shinna, Izet M. Kapetanovicb, Hyuntae Kimc, Moonsun Kimc, Elaine L. Jacobsonc, Myron K. Jacobsonc and Carol E. Greena, ,

a Toxicology and Metabolism Laboratory, SRI International, 333 Ravenswood Ave. Menlo Park, CA 94025, USA

b Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Executive Plaza North, Room 2116, 6130 Executive Blvd., Bethesda, MD 20892-7322, USA

c Department of Pharmacology and Toxicology, College of Pharmacy and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA

Tuesday, 27 July 2010

Niacin

Niacin

Niacin is a vitamin that repairs and prevents damage to skin cells.

Refer the skin care products containing niacin.

Saturday, 4 July 2009

Niacinamide

Niacinamide

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