Nipagin M is a broad spectrum antimicrobial agent designed for preservation of a wide range of cosmetics, toiletries and topical pharmaceuticals. 
Nipagin M is suitable to preserve both rinse- off and leave- on formulations.

Typical use concentrations of Nipagin M is 0.1 – 0.3 %.
Combinations of p- Hydroxybenzoic acid esters, e.g.with Nipasol M, Nipagin A or Nipabutyl exhibit increased activity compared with individual esters.

Nipagin M is freely soluble in most oils, waxes, fatty alcohols, but have relatively low solubility in water.
The low aqueous solubility does not affect the microbiological efficacy of the esters.
Most formulations requiring preservation contain a significant amount of water.
This may mean that Nipagin M cannot readily be added directly to the formulation.
Other methods of incorporation are quite straightforward however, and are listed below.

Dissolving in water
The solubility of Nipagin M increases greatly as the temperature of the water rises. 
Therefore a concentrate may be made up by heating an appropriate quantity of water to 60- 100 °C prior to addition of Nipagin M.
This concentrate may then be added to the formulation, provided that the ester concentration does not exceed its solubility in the formulation at normal ambient temperatures.

Dissolving in organic solvents Nipagin M is readily soluble in polar organic solvents.
Where such a solvent is already part of a formulation an
Nipagin M concentrate may be made up prior to addition.
If a suitable solvent is not already part of the formulation,a highly concentrated solution may be made up e.g. 32 % in Ethanol, which would give insignificant residual levels of ethanol in the end product.

Solubilisation in oils, emulsifiers etc.
Nipagin M is readily soluble in lipophilic ingredients and may be introduced to a formulation by adding to the oil phase with some warming before any emulsification stage. 
In multiphase systems, such as emulsions, it is often advisable to use a combination of aqueous dissolution
with either of the other methods to ensure adequate preservation. 
The ester may be incorporated in the water to its maximum solubility and any further quantities may be dissolved in the oil phase, or solvent, as appropriate.

pH stability
Nipagin M remains fully stable over a wide pH range from 4- 8. In general the lower the pH of the formulation, the more active is Nipagin M. 
That can result in a lower use concentration when the pH of the formulation is more acidic.

Temperature stability
Nipagin M is stable up to 80 °C.

Nipagin M is the best water soluble short-chain Paraben.

Broad spectrum of activity against bacteria and fungi
Low order of toxicity
Effectiveness at low concentrations
Stability over a broad pH-range
Biodegradability at environmental concentrations
Global acceptance in personal care applications

The solubility of Nipagin M in different solvents is illustrated in the following table.

Solvent % (w/w)
Water 10 °C 0.13
Water 25 °C 0.25
Water 80 °C 3.1
Water 100 °C 6.2
Acetone 39
Methanol 37
Ethanol 32
Propylene Glycol 26
Glycerol 3.3
Vegetable oils (arachis) 2.4
Liquid paraffin 0.02

Microbial Activity
Nipagin M exhibits microbiostatic activity against a wide range of bacteria, yeast and mould. 
This is illustrated by the following table which shows the minimum inhibitory concentration (MIC) of Nipagin M against examples of different groups of microorganisms.

Microorganisms MIC level (%)
Gram Negative Bacteria
Pseudomonas aeruginosa 0.20
Escherichia coli 0.10
Klebsiella aerogenes 0.075
Klebsiella pneumoniae 0.10
Serratia marcescens 0.075
Proteus vulgaris 0.10
Salmonella enteritidis 0.15
Salmonella typhi 0.15

Microorganisms MIC level (%)
Gram Positive Bacteria
Stpahylococcus aureus 0.15
Streptococcus haemolyticus 0.10
Bacillus cereus 0.075
Bacillus subtilis 0.10
Lactobacillus buchneri 0.10

Candida albicans 0.10
Saccharomyces cerevisiae 0.10

Aspergillus niger 0.10
Penicillium digitatum 0.05
Rhizopus nigricans 0.05

Storage instructions
The product must be stored in tighly closed container in a cool, well- ventilated, dry place.
Further information on handling, storage and dispatch is given in the EC safety data sheet

Methylparaben, also methyl paraben, one of the parabens, is a preservative with the chemical formula CH3(C6H4(OH)COO). 

Methylparaben is the methyl ester of p-hydroxybenzoic acid.

Natural occurrences
Methylparaben serves as a pheromone for a variety of insects and is a component of queen mandibular pheromone.

It is a pheromone in wolves produced during estrus associated with the behavior of alpha male wolves preventing other males from mounting females in heat.

Methylparaben is an anti-fungal agent often used in a variety of cosmetics and personal-care products. 
It is also used as a food preservative and has the E number E218.

Methylparaben is commonly used as a fungicide in Drosophila food media at 0.1%.[5] To Drosophila, methylparaben is toxic at higher concentrations, has an estrogenic effect (mimicking estrogen in rats and having anti-androgenic activity), and slows the growth rate in the larval and pupal stages at 0.2%.[6]

There is controversy about whether methylparaben or propylparabens are harmful at concentrations typically used in body care or cosmetics. 
Methylparaben and propylparaben are considered generally recognized as safe (GRAS) by the USFDA for food and cosmetic antibacterial preservation.
Methylparaben is readily metabolized by common soil bacteria, making it completely biodegradable.

Methylparaben is readily absorbed from the gastrointestinal tract or through the skin.
It is hydrolyzed to p-hydroxybenzoic acid and rapidly excreted in urine without accumulating in the body.
Acute toxicity studies have shown that methylparaben is practically non-toxic by both oral and parenteral administration in animals.
In a population with normal skin, methylparaben is practically non-irritating and non-sensitizing; however, allergic reactions to ingested parabens have been reported.
A 2008 study found no competitive binding for human estrogen and androgen receptors for methylparaben, but varying levels of competitive binding were seen with butyl- and isobutyl-paraben.

Preferred IUPAC name
Methyl 4-hydroxybenzoate
Other names
Methyl paraben;
Methyl p-hydroxybenzoate;
Methyl parahydroxybenzoate;
Nipagin M;
E number E218; Tegosept; Mycocten

CAS Number: 99-76-3 

Methyl 4-hydroxybenzoate

This information is based on our present state of knowledge and is intended to provide general notes on our products and their uses. 
It should not therefore be construed as guaranteeing specific properties of the products described on their suitability for a particular application. 
Any existing industrial property rights must be observed. 
The quality of our products is guaranteed under our General Conditions of Sale.

4-hydroxybenzoic acid, methyl ester
Methyl 4-hydroxybenzoate
Methyl 4-hydroxybenzoate
methyl 4-hydroxybenzoate
CAS names
Benzoic acid, 4-hydroxy-, methyl ester

IUPAC names
Benzoic acid, 4-hydroxy-, methyl ester
Benzoic acid, p-hydroxy-, methyl ester
Benzoic acid, p-hydroxy-, methyl ester (6CI,8CI), 4-(Carbomethoxy)phenol, 4-(Methoxycarbonyl)phenol, 4-Hydroxybenzoic acid methyl ester, 4-Hydroxymethyl benzoate, Methyl 4-(3'-butenyloxy)benzoate
Methyl 4-Hydroxybenzoate
Methyl 4-hydroxybenzoate
methyl 4-hydroxybenzoate
methyl parabel [INCI]
Methyl Paraben
methylparaben [INCI]
p-Hydroxybenzoic acid, methyl ester

Trade names
Faracide M
Methyl parahydroxybenzoate
Microcare MHB
Paratexin M
Solbrol M

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