PRODUCTS

NIPAGIN M

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.

EC / List no.: 202-785-7
CAS no.: 99-76-3

Synonyms:
Methyl 4-hydroxybenzoate; METHYLPARABEN; 99-76-3; Methyl paraben; Methyl p-hydroxybenzoate; Nipagin; Methyl parahydroxybenzoate; Maseptol; p-Hydroxybenzoic acid methyl ester; p-Methoxycarbonylphenol; 4-Hydroxybenzoic acid methyl ester; Benzoic acid, 4-hydroxy-, methyl ester; p-Carbomethoxyphenol; Tegosept M; Methaben; Metoxyde; Preserval; Metaben; Moldex; Paridol; Septos; Solbrol; Methyl parasept; Methyl butex; Methyl chemosept; Nipagin M; Aseptoform; Methylben; Abiol; Methyl-p-hydroxybenzoate; Preserval M; Solbrol M; 4-(Methoxycarbonyl)phenol; Methyl p-oxybenzoate; 4-Hydroxybenzoic acid, methyl ester; Methyl ester of p-hydroxybenzoic acid; p-Oxybenzoesauremethylester; MFCD00002352; FEMA No. 2710; Benzoic acid, p-hydroxy-, methyl ester; UNII-A2I8C7HI9T; NSC 3827; p-Hydroxybenzoic acid, methyl ester; p-Hydroxybenzoic methyl ester; 4-HYDROXY-BENZOIC ACID METHYL ESTER; Methylester kyseliny p-hydroxybenzoove; A2I8C7HI9T; CHEMBL325372; CHEBI:31835; NCGC00159376-02; NCGC00159376-04; E218; DSSTox_CID_2529; WLN: QR DVO1; DSSTox_RID_76616; DSSTox_GSID_22529; Methyl 4-hydroxybenzoate, 99%; Caswell No. 573PP; FEMA Number 2710; CAS-99-76-3; SMR000036660; CCRIS 3946

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. 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. 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. 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. Nipagin M is stable up to 80 °C.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. 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 is a 4-hydroxybenzoate ester resulting from the formal condensation of the carboxy group of 4-hydroxybenzoic acid with methanol. It is the most frequently used antimicrobial preservative in cosmetics. It occurs naturally in several fruits, particularly in blueberries. It has a role as a plant metabolite, an antimicrobial food preservative, a neuroprotective agent and an antifungal agent.Almost odourless, small colourless crystals or white crystalline powder.
Nipagin™ M is a broad spectrum antimicrobial agent designed for preservation of a wide range of cosmetics, toiletries and topical pharmaceuticals. It is suitable to preserve both rinse-off and leave-on formulations. This product is supplied as a white, crystalline powder.Methylparaben. Nipagin® M is a methyl 4-hydroxybenzoate. Acts as a preservative. Contains best water soluble short-chain Paraben. Nipagin® M is used in showers, liquid soaps, shampoos, syndets, bar soaps, antiperspirants & deodorants, wet wipes, hair conditioners, decorative cosmetics, creams, lotions and hair styling products.Nipagin M is the best water soluble short-chain Paraben.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. 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

Benefits
Broad spectrum of activity against bacteria and fungi
Low order of toxicity
Effectiveness at low concentrations
Stability over a broad pH-range
Water-soluble
Biodegradability at environmental concentrations
Global acceptance in personal care applications
Europe: maximum concentration 0.4 % (acid) for 1
ester, and 0.8 % (acid) for mixtures of esters, no restrictions, Annex VI, 76/768/EEC.
Japan: maximum concentration 1 % in cosmetic product, no restrictions.
USA: considered safe as used by Cosmetic Ingredient
Review (1984).

Uses
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.

Applications
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.

Incorporation
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.

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

Chemical name: Methyl 4-Hydroxybenzoate
Chemical structure
INCI designation
Methylparaben
Product properties
Appearance (20°C): White, crystalline powder.
Chemical and physical data
Melting point: 125 - 128 oC
Assayacc. BP/PH.Eur: 98.0 - 102.0 %

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

Yeasts
Candida albicans 0.10
Saccharomyces cerevisiae 0.10

Molds
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.

Uses
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]

Safety
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.