月桂酰精氨酸乙酯盐酸盐

1 Introduction

1.1 Description

Chemical Name: Ethyl-N^α-lauroyl-L-arginate• HCl
Synonyms: EthylLauroyl Arginate HCl, lauramide arginate ethyl ester,
LAE, Lauric arginate
INS No. :243
CAS No.: 60372-77-2
Ethyl-N^α-lauroyl-L-arginate • HCl is an antimicrobial widely used infood and cosmetics industries. It is a cationic surfactant that inhibits theproliferation of a wide variety of microorganisms, including both Gram positiveand Gram negative bacteria，molds and yeasts.
Ithas been evaluated for food safety as antimicrobial in food by the U.S. Foodand Drug Administration (FDA) in 2005 and as a food preservative by theEuropean Food Safety Authority (EFSA) in 2007.

1.2 Applications

Food Sector
Ethyl-N^α-lauroyl-L-arginate • HCl improvesthe safety of food products，extending their useful life，it can be used in meat products，drinks and juices，cheese，fish products，sauces，ready-made-meals，etc.
Cosmetics Sector
Ethyl-N^α-lauroyl-L-arginate • HCl offershigh antimicrobial activity in applications such as: moisturizing creams,facial soaps, makeup removing milks，toners，deodorants，shampoos，etc. Its INCI name is Ethyllauroyl arginate HCl.

2. Physical and Chemical Properties

2.1 Physical and Chemical Properties of dehydrated LAE

Test	Result
Appearance	White hygroscopic power
Molecular weight	421.02 g/mol
Melting temperature	50.5 to 58.0℃
Boiling temperature	Decomposes from 107℃
Relative density	1.11
Vapour pressure	5.45 ×10-4 Pa at 25℃
Surface tension	25.43 m N/m for a 1 g/l aqueous solution at 19℃
Water solubility	Greater than 247g/Kg at 20"C
Partition coefficient	1.43 at 20℃
Flammability (solids)	Not highly flammable
Explosive properties	Not explosive
Relative self-ignition temperature for solids	Does not self ignite
Oxidizing properties	Not oxidizing
Particle size distribution	0% below 10µm
Soli adsorption coefficient	K∝=58.0

2.2 ProductStability

Stability Test	Results
In a closed dark at 25℃ for 10 days and 5,6,10,and 12 months	No significant degradation was found after 12 months
At 30,50,75,100 and 121℃ for 1 and 5 hours	Stable for 5hours at ≤100℃ and for 1 hour at 121℃
At 4,25 and 50℃ and pH 0.5, 1.0, 1.5, 2.0, 2.5, 3.0and 3.5 for 10-52 days	At 4℃, no significant degradation if pH>1.5; at 25℃, no significant degradation if pH>2.5; at 50℃, no significant degradation if pH>3.0
Stability for 1-61 days after application to cooked ham	No significant degradation was found after 61 days at 4℃

3. Antimicrobial Efficacy

3.1 Mode of Action

Theactive ingredient，Ethyl-N^α-Iauroyl-L-arginate hydrochloride is a cationicsurfactant that inhibits the proliferation of a wide variety of microorganisms， including both Grampositive and Gram negative bacteria，molds，and yeasts. This inhibitory effect isa direct consequence of its chemical properties as a surface-active compoundthat leads to changes in the conductivity and solubility of solutions.Negatively charged materials， such as bacterial enzymes and membrane proteins， attract cationic surfactants， which degrade orsolubilize cell membranes， leading to loss of membrane potential， altering cell permeability andleaking cellular constituents. These changes result in the arrest of growth orcell lysis.

3.2 Ethyl-N^α-Iauroyl-L-arginate· HCl vs Nitrites

Example: LAURIC ARG I NATE AS A PRESERVATIVE FORMARINATED MEAT
Treatments
Three lots of marinated meat were produced:
The control lot (BI)，produced without any preservative.
Treatment with nitrites (NO₂). NaNO₂ was added at doses of 150 mg/kg of marinated meat. NaNO₂was addedas an ingredient more of the marinated solid.
Treatment with Lauric arginate (Ethyl-N^α-Iauroyl-L-arginate•HCl ,LAE).
LAE was added by dipping the fresh beef in a bath at1% of LAE in deionised water during 30 seconds. Fresh beef treated in this waywas used as described in the recipe.

Days	Sample	BI	NO2	LAE	Days	Sample	BI	NO2	LAE
	1	4.5	4.3	3.8		1	7.2	6.8	4.7
	2	4.3	4.5	3.7		2	7.2	7.1	5.5
	3	4.5	4.7	3.5		3	7.3	6.8	5.9
1	4	4.7	4.7	3.9	14	4	7.4	6.5	4.7
	5	4.8	4.5	3.7		5	7.4	6.1	3.9
	X	4.5	4.5	3.7		X	7.3	6.6	4.9
	Α	0.2	0.2	0.1		α	0.1	0.4	0.8
	1	4.5	4.3	4.0		1	8.4	7.7	6.1
	2	4.9	4.8	3.9		2	8.1	7.8	7.0
	3	4.7	4.2	3.7		3	8.4	7.1	5.9
3	4	4.5	4.7	3.7	17	4	8.4	7.3	5.9
	5	4.5	4.3	3.8		5	7.9	6.6	6.1
	X	4.6	4.4	3.8		X	8.2	7.3	6.2
	α	0.2	0.3	0.1		α	0.2	0.5	0.4
	1	4.2	4.1	3.7		1	8.4	8.3	5.6
	2	4.8	4.1	3.7		2	8.2	8.2	7.9
	3	4.8	4.7	3.8		3	8.6	7.9	5.9
7	4	4.9	4.5	3.5	21	4	8.7	8.3	6.4
	5	4.5	4.5	3.8		5	8.2	7.3	7.1
	X	4.6	4.4	3.7		X	8.4	8.0	6.6
	α	0.3	0.2	0.1		α	0.2	0.4	0.9
	1	6.9	4.8	3.9		1	8.5	8.7	7.7
	2	6.8	4.7	4.0		2	8.7	8.6	7.4
	3	6.7	4.9	3.9		3	8.5	8.3	6.9
10	4	6.9	4.7	3.9	24	4	8.7	8.5	7.7
	5	6.8	4.5	4.1		5	8.1	7.9	7.2
	X	6.8	4.7	4.0		X	8.5	8.4	7.4
	α	0.1	0.1	0.1		α	0.3	0.3	0.4

Conclusions
Microbiologicalresults show that LAE can reduce significantly the growth of natural occurringflora in the marinated meat. According to the previous conclusion，LAE could improve themicrobiological stability of marinated meat and guarantee the maintenance ofall its characteristics once it is consumed.
1. LAE is a good preservative for marinated meat.
2. LAE is a good substitute for nitrites and，nitrates in the preservationof marinated meat.

4 Toxicological Safety and Human Studies

4.1 In Vivo Investigations into the Metabolism of LAE inHumans
Thisstudy was conducted under Good Laboratory Practice (GLP) standards，as specified in the UK(Statutory Instrument 1999 No.3 106，as amended by Statutory Instrument2004 No. 994)， EC (Official Journal No.L 77/8， as amended in OfficialJournal No. L50/44)，and OECD (ENV/MC/CHEM(98)17). It was designed to investigate the rate andextent of metabolism of LAE in humans. In the first phase (Centra Labs ClinicalResearch 2005a)，two adult males received a single oral dose of 2.5 mg/kg bw LAE as a 25%solution in propylene glycol. Their blood was sampled at 0 h (pre-dose)，at 5，10，15，and 30 minutes，and at 1，2，4，8，12，and 24 hours postadministration. The collected plasma was isolated and extracted with methanol;the extract and residue were analyzed by HPLC with limits of quantification of1ng/d for LAE and its major metabolite, LAS, and 20 ng/mL for arginine
Asshown in Figure 1, LAE was not detected at any point and the LAS and argininelevels，declined to non-detectablelevels within 12 hours.

Inthe second phase (Centra Labs Clinical Research 2005b)，four adult males wereadministered a single dose of 1.5mg/kg bw LAE as a 25% solution in propyleneglycol. The methods were thesame as in the first study.
Asshown in Figure 2,the result were also similar: LAE was not detected，and the concentrations ofboth LAS and arginine decreased to undetectable levels within 12 hours of administration.

Regulatory Status

A.Center for Food Safety and Applied Nutrition，U.S. Food and Drug Administration(2005) Agency Response Letter GRAS Notice No. GRN 000164，http://cfsan.fda.gov/~rdb/opa-g164.html.
B.Scientific Committee on Consumer Products，European Commission (2005) Opinion onEthyl Lauroyl Arginate，COLIPA No P95， SCCP/0837/04.
C.European Food Safety Authority， 2007. Opinion of the Scientific Panel on Food Additives，Flavourings，Processing Aids andMaterials in Contact with Food on a request from the Commission related to anapplication on the use of ethyl lauroyl arginate as a food additive，The EFSA Journal，511，1-27.
D.Food StandardsAustraliaNew Zealand，Application A1015 EthylLauroyl Arginate As A Food Additive Explanatory Statement. This Applicationseeks to amend Standard 1.3.1 Food Additives of the Australia New Zealand FoodStandards Code (the Code) to include a new food preservative，ethyl lauroyl arginate.

5. Application Example

Control of Listeria monocytogenes on Cooked Cured Hamby Formulation with a
Lactate-Diacetate Blend and Surface Treatment with LAE.
Control ham with no added antimicrobials (control)
Ham formulated with 1.68% potassium lactate and 0.12%sodium diacetate (PLSD)
Control ham with 0.07% LAE as a surface treatment
Ham formulated with PLSD and LAE surface treatment
surface treatment (sprayed in bag and distributedacross meat surface during vacuum packing) (PLSD+ LAE)


Conclusions: Use of a post-Lethality inactivationtreatment such as LAE in combination with a growth inhibitor such as a lactate-diacetate blend in cooked cured ham results in reduction of the pathogen leveland continued suppression of growth when stored under vacuum at refrigeration(4 ℃).
Lauricarginate ethyl ester; lauramide arginine ethyl ester;ethyl-Nα-lauroyl-L-arginate·HCl; LAE; INS No. 243.
Physicochemical characterization
Ethyl lauroyl arginate is a white powder and its solubility in water at 20ºC is greater than247g/kg.Ethyl lauroyl arginate is soluble up to 20% in propyleneglycol, glycerin and ethanol. The pH of 1 % aqueous solution is in the range of3.64 to 4.25.
Chemical characterization
Ethyl-N^α-lauroyl-L-arginate HCl is the active ingredient of ethyl lauroyl arginate and its contents are >85%. Lauric acid, L-arginine HCl and ethanol are materials and their residual amounts are <5.0%, <3% and <0.5%, respectively. N^α-Lauroyl-L-arginine, ethyl laurate and ethyl arginate 2HCl are by-products andtheir contents are <3%, 3%, <1%, respectively. Other three minor by-products share the structure of ethyl-N^α-lauroyl-L-arginate HCl but have an additional lauroyl group. Water contents are <5%. Ashes heated at 700° are mainly NaCl and their amounts are <2%. Arsenic, cadmium, lead and mercury are notdetected.
Functional uses
Ethyl lauroyl arginate is used as preservative. Ethyl-N^α-lauroyl-L-arginate HCl which is a cationic surfactant has a wide spectrum of activity against Gram positive and negative bacteria, yeasts and moulds. It acts on cell membranesand the cytoplasm, and inhibits the growth of populations but in no case is celllysis observed under the conditions studied. It can be used in a wide range of foods.
Reaction and fate infoods
The stability of ethyl-N^α-lauroyl-L-arginate HCl is evaluated in different food matrices. It is found to be stable throughout the duration of the study in allprocessed food matrices.