Hemina Skin Rebuilding and Reconditioning Therapy: Treating Ichthyosis & Xerosis. Heyde E. Lopez Monica Sanders Erin Sposato

Transcription

1 Hemina Skin Rebuilding and Reconditioning Therapy: Treating Ichthyosis & Xerosis Heyde E. Lopez Monica Sanders Erin Sposato

2 Purpose To design a moisturizing package that treats ichthyosis skin disorder and xerosis (dry skin) May target other skin disorders

3 Agenda Anatomy The Skin Disorder Treatment Our Original Product Substitutes and Modeling Consumer Attitudes Demand Model Manufacturing Economic Analysis

4 Anatomy

5 The Human Skin Self-contained organ that exists as a semipermeable barrier layer Two components with interdependent functions: epidermis and dermis Source:

6 Epidermis ~40 µm thick Four (or five) layers 1. Stratum corneum 2. (Stratum lucidium) 3. Stratum granulosum 4. Stratum spinosum 5. Stratum basale Basal membrane (6) Source:

7 Stratum Corneum Generally ~10-15 µm thick Tough but pliable quality given by keratin layers of corneocytes embedded in a matrix of lamellar lipids

8 Stratum Corneum Brick and mortar structure Corneocytes (bricks) Anucleated, non-viable, keratin-rich cells Hydrophilic Lipid lamellae (mortar) Tight lateral packing Hydrophobic Ceramides (40-50%) Cholesterol (25%) Fatty acids (10-15%) Other lipids, such as cholesterol sulfate (<5%) Source:

9 Stratum Corneum Cohesion Desmosomes - main cohesive forces Protein bridges Attach to cell envelopes and lock into position Covalent bonding of lipids in matrix van der Waals forces hold the lipid lamellae and the corneocytes Source:

10 Desquamation Corneocytes break apart and are lost Enzymatic process dissolves desmosomes These proteolytic enzymes are present in wellhydrated SC Defective desquamation - corneocytes build up

11 Natural Moisturizing Factor High concentration inside the corneocytes Some in the intercellular lipid matrix Humectants - absorb water Allow for the outermost layers of the SC to remain hydrated

12 Stratum Corneum Desmosomes Lipid Matrix NMF Components Lactic acid Urea Urocanic acid PCA Citrates Sugars Corneocytes

13 Types of diffusion through skin Percutaneous difussion: Rate and extent that a chemical is absorbed into and through the skin Transepidermal water loss (TEWL) Passage of water from the body through the skin into the outside environment

14 Percutaneous Diffusion SC is rate-limiting step Corneocytes Lipid lamellae Intercellular diffusion through the lipid lamellae *rate determining component of the SC barrier Transcellular diffusion through both the corneocytes and lipid lamellae Diffusion through appendages (hair follicles and sweat ducts)

15 The Skin Disorder

16 Xerosis Dry skin of a normal or non-pathological state Low water content in SC Dry and itchy skin Occurs when natural moisture is drawn out Can be due to cold weather or exposure to too much water

17 Ichthyosis What is it? A family of disorders in the production and/or desquamation of epidermal cells Generically characterized by dry, thickening, scaly skin Figure 1: Ichthyosis Vulgaris Figure 2: Ichthyosis Vulgaris Source: Geneva Foundation for Medical Education and Research,

18 Ichthyosis Incidence Several ichthyoses exist most affect only one person out of tens of thousands Most common forms Ichthyosis Vulgaris Incidence: 1 in 250 Source:

19 Ichthyosis Vulgaris Reduced water content affects the enzymatic reactions governing desquamation Genetic defects inherited Rare cases are acquired AIDS and cancer Currently, there is no cure Symptomatic treatment

20 Treatment

21 Treatment To better treat the disorder, it is necessary to improve skin function by Promoting desquamation Replacing components such as NMF Restoring the lipid barrier Current treatments focus on only one step of the cascade of dehydration No current product that is offered as a package to treat different causes of poor hydration

22 Current Treatment Many topically applied moisturizers work to trap water - occlusives Can be very greasy unpleasant to consumer Some ingredients promote desquamation Keratolytic agents such as lactic acid Current treatment has disadvantages Very temporary Focuses on one symptom

23 Moisturizers Maintain hydration and smoothness of the skin Putting water back into the skin is no longer the only method for hydrating the skin Active ingredients can improve abnormal skin function and structure

24 Moisturizer Components Active Ingredients Occlusives Emollients Retard water loss by forming a layer on the surface of skin Fill intercellular spaces with droplets of oil Humectants Exfoliants Draw water from the dermis and from air by hydrogen bonding into the epidermis Increase sloughing of dead cells on the surface of the skin

25 Moisturizer Components Complementary Ingredients Emulsifying agents Preservatives Thickeners ph Adjustors Antioxidants Help the emulsion Prevent microbiologic contamination Help reach a specific viscosity Adjust the ph of the moisturizer Prevent oxidative damage in the skin

26 Moisturizer Technology Liposomes - Cheap and simple to manufacture Microemulsions - Droplets are greater than 0.5 nm in size - High surface area allow Advantages effective transport of active to skin W/O O/W nm diameter Low toxicity Uptake by endocytosis (can fuse with cell wall) Biodegradable and non-toxic in nature Replace surfactants and emulsifiers Disadvantages Short circulation half-time

27 Manufacturing Delivery Technology 1. Inverted emulsion with aqueous solution to encapsulate active 2. Emulsified in an organic continuous phase PEG coating 3. Techniques to control size particle and encapsulation yield (sonication and extrusion) Bath sonicator

28 Our Original Product

29 Skin Rebuilding and Reconditioning Therapy Package of 3 separate products: 1. Pre-Shower Lotion (16 oz) - Promotes desquamation 2. Shower Gel (20 oz) - Restores NMF and exfoliates 3. After-Shower Lotion (16 oz) - Rebuilds skin barrier and leaves skin smooth and hydrated

30 Target of Our Product Desmosomes Lipid Matrix NMF Components Lactic acid Urea Urocanic acid PCA Citrates Sugars Corneocytes Water

31 Skin Rebuilding and Reconditioning Therapy Our package works as a system of treatment that will surpass current treatments because ours will rebuild skin function producing a longer period of relief Rather than replacing water lost by the SC, our products will give the skin the tools it needs to prevent future dehydration and scaling

32 Original Formulation Active ingredients based on the intended function of each package product Pre-Shower After-Shower Gel Lotion Lotion - - Ammonium Lactic Ceramide acid lactate Intended to restore the - γ-linoleic acid These lipid ingredients matrix are found Effective - Urea for treatment of ichthyotic disorders by naturally in the skin as helping - - Sodium Cholesterol to shed PCAthe built up layers of corneocytes components of the NMF - - Urocanic Dimethicone acid Humectants that will absorb - Lanolin water into the skin - Citric Acid

33 FDA Regulations FDA does not regulate cosmetics as it does to drugs But.. Manufacturers are not obligated to pre-register their Cosmetics products are before defined they as go articles into market applied to the body in any manner...for cleansing, beautifying, promoting attractiveness, or altering the appearance Cosmetic producers must keep ingredients below the regulated concentration given in the Cosmetic Ingredients Review

34 Original Formulation: Pre-Shower Lotion Pre-Shower Lotion Formulation Ingredient Water Ammonium Lactate Retinyl Palmitate Jojoba Oil PEG-4 Cetyl Alcohol Octyldodecanol Phenoxyethanol Maleic Acid Percent (%) Function Solvent Desquamation Antioxidant Emollient Emollient/Liposome Formation Emulsifier Thickener Preservative ph Adjuster

35 Original Formulation: Shower Gel Ingredient Shower Gel Formulation Percent % Function Water 52 Solvent Polysorbate Surfactant Cocoamidopropyl Betaine 5 Surfactant Lactic Acid 4 Exfollient/NMF Urea 4 NMF Sodium PCA 3 NMF Urocanic Acid 3 NMF Citric Acid 3 NMF Oleic Acid 3 Emollient/Thickener Cetyl Alcohol Emulsifier Phenolxyethanol 0.2 Preservative Maleic Acid ph Adjustor

36 Original Formulation: After-Shower Lotion After-Shower Lotion Formulation Ingredient Water Dimethicone Lanolin PEG-4 Cetyl Alcohol Ceramide Isostearic Acid Palm Oil γ-linoleic Acid Cholesterol Phenoxyethanol Maleic Acid Percent % Function Solvent Humectant Humectant Emollient/Liposome Formation Emulsifier SC Lipid/Humectant Thickener Emollient SC Lipid SC Lipid Preservative ph Adjustor

37 Cost for the Package Cost (million $) Raw Material Cost/yr Total Product Cost/yr Annual Product Revenue/yr NPW

38 Substitutes and Modeling Consumer Attitudes

39 Substitute Ingredients Ingredients costing more than $10^5 / year were considered for replacement with less expensive chemicals serving the same purpose Active ingredients were not substituted PEG was also not substituted - liposome formation

40 Pre-Shower Lotion Substitutes Material Deionized Water Ammonium Lactate* Jojoba Oil PEG Octyldodecanol Retinyl Palmitate (Vitamin A Palmitate) Cetyl Alcohol Phenoxyethanol Maleic Acid Function Solvent Desquamation Emollient Emulsifier/Liposome Formation Thickener Antioxidant Emulsifier Preservative ph Adjuster Fragrance Substitutes Castor Oil Paraffin Oil Ascorbic Acid Polysorbate Peppermint Oil

41 Shower Gel Substitutes Material Deionized Water Polysorbate-20 Cocoamidopropyl Betaine Lactic Acid Urea Sodium PCA Urocanic Acid Citric Acid Oleic Acid Cetyl Alcohol Phenoxyethanol Maleic Acid Function Solvent Surfactant Surfactant NMF NMF NMF NMF NMF Emollient/Thickener Emulsifier Preservative ph Adjuster Fragrance Substitutes Polysorbate Peppermint Oil

42 After-Shower Lotion Material Deionized Water Dimethicone Lanolin PEG Cetyl Alcohol Isostearic Acid Palm Oil Ceramide γ-linoleic acid Cholesterol Phenoxyethanol Maleic Acid Function Solvent Humectant Humectant/Emollient Emollient/Liposome Formation Emulsifier Thickener Thickener SC Lipid/Emollient SC Lipid SC Lipid Preservative ph Adjustor Fragrance Substitutes Sorbitol Isopropyl Palmitate Polysorbate Paraffin Oil Peppermint Oil

43 Consumer Preferences Based on Physical Properties

44 Happiness Model Optimizes relative happiness by determining formulation based on 4 factors: Effectiveness Spreadability Thickness Creaminess Related Based on to surface curing tension ability of active ingredients and PEG Thickness Creaminess = = (Viscosity) (Smoothness 0.5 * Thickness) 0.5 [ P] These Viscosity concentrations *( found or ) 4 σ = ρ are estimated weighted for based all on ingredients function L ρg Smoothness 1000 = (Coefficient of Friction) 0.5 Curing Ideal values ability determined viscosity from: experiment and ( C ) [P] determined from structure general recommendations ρ G neglected at low pressure C w 0 0 w C * w DM Ideal Cw HM

45 Happiness Model Pre-Shower Pre-Shower Smoothness Crea m- iness Effecti veness Spreadability Fraction CIR allowed maximum Viscos -ity µ (cp) Thick -ness µ^.5 (cp^.5 ) Grease Sense upon Application Coefficient of friction Ideal Value Curing ability C wo (g/l) Surface tension Constituent Ideal values Deionized Water 55% S 0 72 Ammonium Lactate* 10% S Jojoba Oil 5% I Total Mixture Value Happiness percentage Weight of variable Relative happiness= 0.783

46 Diffusion Model Accounts for mass transport through: Oil Phase Water Phase Protein Phase C w 0 0 w C * w DM Ideal Cw ( C ) HM Disregards: Diffusion through the appendages since it accounts for 0.1% of the total surface area of the skin TEWL since it is constant and represents a very small portion of the water contained by the body

47 Diffusion Model of the SC This equation was derived using a diffusion model based on Fick s Law C C x w = 1 w Lsc 2 π n= 1 sin Dscn π t 2 R L This model is a function of time and location in the skin 1 n nπx L sc e sc 2 sc 2 10 minutes- Pre-shower Lotion 3 minutes- Shower Gel 12 minutes- Post-Shower Lotion 5 µm- Pre-shower Lotion 15 µm- Shower Gel 15 µm- After-Shower

48 Demand Model

49 Market Trends Patients will always need a product to treat the disorder No cure Demand should never decrease No cure Approximate constant number of people affected by the disorder

50 Demand Model β p β = d d d H H = D d = α p d α D p2 = α p + β p 1 2 Constants Demand Constants beta alpha Time (year)

51 Distribution and Advertising Promoting our package to the Icthyosis community by: Free samples to: General practitioners and dermatologists Patients registered on Ichthyosis registries Advertisements in: Icthyosis organization websites Posting in medical offices

52 Manufacturing

53 Process Design

54 Equipment Equipment Tank 1: Shower Gel Tank 2: Lotion Tank 3: Lotion Colloid Mill Bath Sonicator Homogenizer 2 Pumps Total Equipment Cost Specifications 15.1 m m m hp 115 V 100 L/hr m 3 /s Cost ($) 43,750 38,700 38,700 15, ,500 5,500 $154,000

55 Economic Analysis

56 Raw Material Cost Original Raw Material Cost Substitute Raw Material Cost Cost (million $/year) Pre-Shower Shower Gel After Shower Total Cost (million $/yr) PreShower Shower Gel After Shower Total Year Year

57 Economic Evaluation Optimized Original Formulation Optimized Substitute Formulation Equipment Cost Equipment Cost Fixed Capital Investment Fixed Capital Investment Total Capital Investment Total Capital Investment Net Profit Net Profit NPW NPW 28.55

58 Net Present Worth vs Package Price NPW (million $)) Optimal Formulation NPW vs Package Price Price per Package ($) NPW (million $) Substitutes NPW vs Package Price Price per Package ($)

59 Final Formulation Pre-Shower Shower Gel After-Shower Ingredient % Ingredient % Ingredient % Deoinized Water 55 Deoinized Water Deoinized Water 50 Ammonium Lactate 10 Sodium PCA 3 Isopropyl palmitate 2 Ascorbic Acid Lactic Acid 1 Sorbitol 2 Castor Oil Urocanic Acid 1.5 Ceramide Polysorbate Citric Acid γ-linoleic acid Paraffin Oil Urea 9 Cholesterol Maleic acid Polysorbate Polysorbate Phenoxyethanol Cocoamidopropyl Betaine 5 Paraffin Oil 10 PEG Oleic Acid 6 Isostearic Acid 5 Peppermint Oil Phenoxyethanol 1 Maleic acid Maleic acid PEG 15 Peppermint Oil Peppermint Oil Phenoxyethanol 0.001

60 Questions?