A SolventA Solvent--Free Free BiocatalyticBiocatalytic Process Process for Cosmetic & Personal Care Ingredientsfor Cosmetic & Personal Care Ingredients

Green Chemistry and Engineering Conference, 23 June 2009Green Chemistry and Engineering Conference, 23 June 2009

Stephanie K. Stephanie K. ClendennenClendennen, Ph.D.& Neil W. Boaz, Ph.D., Ph.D.& Neil W. Boaz, Ph.D.

Eastman Chemical CompanyEastman Chemical Company

Cosmetic ingredients: Esters

Category

ActivesPreservativesSunscreensFilm formers

<1%

Esters are a class of cosmetic and personal care ingredients represented across functional categories.

An example of an active is retinol, a proven “anti-aging” ingredient that can Film formers

ExfoliantsSurfactantsThickenersEmulsifiersEmollientsHumectantsSolvents>10%

proven “anti-aging” ingredient that can irritate skin.

Esterification can stabilize retinol and reduce its irritation potential.

2 Making retinyl esters�

Acid chloride (or anhydride) esterification:

R1 Cl

O

+ R23N R NR2

3

O

+

+ R-OH

Cl-

R1 OR

O

+ R23NH+ Cl-

product

b d t

solvent

Process comparison: Retinyl esters Conventional

Biocatalyticby-product

3Solvent is used in the reaction and for purification.

Process comparison: Retinyl esters Twelve Principles of Green Chemistry were applied to the process.

US Patent allowed4

Idebenone esters

Idebenone is an effective antioxidant and a new anti-aging ingredient. A potential drawback of idebenone is irritation.

Idebenone esters were prepared by enzymatic esterification & tested.

5 In vitro assays predict irritation potential.

A long-chain idebenone ester was compared to idebenone in an in vitro

cytotoxicity assay.

Idebenone ester cytotoxicity

80

100

120 Idebenone Ester

Cell Viability

(% of Control)

The idebenone ester is significantly less cytotoxic than idebenone.

0 200 400 600 800 10000

20

40

60

80

Idebenone

Concentration (µM)

Cell Viability

(% of Control)

Mouse

melanocytes;

MTT assay.

6 The idebenone ester process was optimized.

Process comparison: Idebenone esters

Biocatalytic

Process 1

Biocatalytic

Process 2

Biocatalytic

Process 3

Product quality

Yield 98% 98% 99%

Assay 98.4% 98.3% 98.3%

Residual idebenone 0.2% 0.4% 0.6%Residual idebenone 0.2% 0.4% 0.6%

Residual acid 0.2% 0.3% 0.3%

Reaction Solvent

(Liters /kg product)2.87 0 0

Isolation Solvent

(Liters /kg product)7.47 3.37 0

Total solvent

(Liters/kg product)10.34 3.37 0.00

Ready to practice solvent-free.7

Alcohol Reactant Fatty Acid Reactant

Solvent-free biocatalysis

Reaction product is substantially pure, no further processing is required.

Boaz & Clendennen, Cosmetics & Toiletries Magazine, in press.8

Process benefits & impact

� Solvent-free process: no trace solvent residue, reduces purification cost/energy

� High selectivity: low waste, unique additions

� Modest temperature: low energy consumption, minimize � Modest temperature: low energy consumption, minimize oxidative by-products (& color), sensitive materials OK

� Renewable biocatalyst: immobilized for complete removal

� Flexible: many innovative products can be made, raises possibility of product customization

� Global environmental benefit is limited by volume.

9 “Actives” are low volume ingredients.

� Estimate for “actives” is ~1 kMT

� Regional demand for emollient esters:

Cosmetic esters market

Emollient estersEmollient esters VolumeVolume((kMTkMT))

Revenue Revenue ($M)($M)

� Worldwide market for all C&PC esters to $1.8B by 2010 or ~500 kMT

North America 19 53

Europe 32 120

Total 51 173

Sources: 2008 Global Industry Analysis; SRI Consulting Cosmetic Report 2007

10 Look at emollient esters.

Process comparison: Emollient esters

Conventional

11

Reaction temperature is a differentiator.

Biocatalytic

catalyst(re-used)

by-products

volatiles

steam

reaction

deodorizing

raw materials

catalyst(re-used)

Conventional Biocatalytic

inputs raw materials

reaction

outputs

drying

Process comparison: Emollient esters

liquid

outputs

Adapted from Veit, 2004, Eng. Life Sci. 4: 508-511.

100-150oC

>150oC

<100oCliquid

filter aidsolid

drying

filtration

packaging

bleaching

packaging

Batch Continuous

12

Process benefits & impact

� High selectivity: low waste, unique additions

� Modest temperature: minimize oxidative by-products, odor & color, sensitive materials OK

� Renewable biocatalyst: immobilized for complete removal

� Flexible: many innovative products can be produced, allows product customization

� Global environmental benefit is limited by volume

� Continuous: advantaged over conventional & batch synthesis in water use, capital / smaller footprint, energy use.

13 Energy use was compared.

Estimated energy and greenhouse gas savingsper MT of emollient ester

Units ConventionalProcess

Eastman EnzymaticProcess

Savings

Methodology from Thum & Oxenboll, “Biocatalysis: A sustainable process for production of cosmetic ingredients,” IFSCC Congress 2006, Osaka.

Process

Without heat

integration

With heatintegration

Without heat

integration

With heatintegration

Energy (GJ) 4.50 0.84 0.55 77% 86%

Greenhouse Gas

(kg CO2

equivalents)304 57 38 77% 86%

As a reference point, burning 1 gallon of gasoline releases ~10 kg CO2.

14 How good is that?

Emollient Esters Regional Demand

Cosmetic Esters Global Forecast

2010

10,000

100,000

1,000,000

GH

G S

avin

gs (M

T C

O2 e

quiv

ale

nts

)Estimated greenhouse gas potential savings*

based on product volume

Batch Scale

EastmanContinuous Process

Regional Demand 2007

1

10

100

1,000

1 10 100 1,000 10,000 100,000 1,000,000

GH

G S

avin

gs (M

T C

O2 e

quiv

ale

nts

)

Volume (MT)

*Difference between conventional and enzymatic processes.15

Summary

� Biocatalysis is inherently green.

� Solvent-free is greener.

� Green is good for business.

� A solvent-free biocatalytic process is good for the environment.

� The overall benefit is proportional to product volume.

16

Thank you

and Marcie Natale, Sandra Reid, Jeff Clauson, Jim McCaulley

and Robert Lin, Mark Shelton, Michael Wempe.

17

For more information:

www.eastman.com/GreenProcess