Uses of cooling agents
Natural cooling agents such as menthol, menthone, methyl acetate and peppermint oil are used to produce a feeling of coolness and freshness while providing a mint scent. They are widely used in daily products such as shower gels and shampoos. Due to the irritating effect of these cooling agents on the eyes and nose and the need to use larger doses, their use in food flavors is limited. Their application in food is mainly limited to chewing gum and mints. Only in such products are they produced by The "non-cooling effect" associated with cooling agents is generally acceptable.
In order to apply cooling agents to other product areas and produce chewing gum and other types of products with flavors other than mint, the development of new cooling agents is urgent and has become a very challenging task. Since the 1970s, various synthetic products with a cooling sensation have been developed and widely used in the edible flavor industry. Following the pioneering work of Watson and colleagues at Wilkinson Sword in the field of synthetic cooling agents, research in this area has attracted increasing attention. Compared to menthol, these cooling agents provide a strong cooling sensation without the burning sensation of menthol when used in high doses. In addition, since these cooling agents have almost no bitterness and mint aroma, they can be used in the formulation of non-mint flavored food flavors. These cooling agents also have a synergistic effect when used with menthol, creating a very distinctive sensation.
The skin's cool receptors are at the base of the epidermis, 0.1 to 0.2 mm below the skin surface, and have a diameter of about 1 mm. When the temperature drops to about 32°C, the cold receptor begins to emit signals. The lower the temperature, the stronger the signal. When the temperature drops below 13°C, you will feel pain, but the pain is felt through different receptors. The mouth may be more sensitive to cold sensations than the outer skin due to its easier penetration. The cooling sensation produced by menthol is thought to be caused by a decrease in Ca2+ conductivity.
The synergistic effect of ambient temperature and molecules has a significant impact on the cooling sensation. For example, low temperatures can enhance the cooling sensation of menthol, while high temperatures can do the opposite. In addition, the cooling sensation is also related to the sensitivity of the individual. Taking menthol as an example, the change in oral threshold is 0.02~10 μg, and most people belong to the relatively sensitive group.
Cooling agents are typically soluble in edible essential oils and bases and are typically mixed well before use in the end product. The amount of cooling agent used depends on the product being applied and often varies widely. Among food flavors, chewing gum and toothpaste have the highest usage, followed by candies and throat lozenges, and other soft drinks and products with high water content have lower usage. In addition, these cooling agents work best in polar systems, such as beverages than chewing gum. Therefore, in some products where the application of cooling agents is difficult, the cooling agents are usually made into sugar coatings to overcome the lipophilicity of the matrix.
Molecular structural characteristics of cooling agents
Cooling agent molecules usually have groups that can form hydrogen bonds, a compact carbon chain skeleton and an appropriate hydrophilic-lipophilic balance value. The relative molecular mass is usually between 150 and 350. The common characteristic of chemical cooling agents is that they are not likely to produce cooling fatigue. As long as they come into contact with receptors in the mouth or skin, they will always produce a cooling sensation. For some reason, amide cooling agents generally produce a cooling sensation faster than nitrogen-free ones, with the exception of menthol.
The relationship between the molecular structure and activity of cooling agents is not very clear so far. As mentioned earlier, cooling agent molecules often share some common properties. These characteristics can be used to guide the design of cooling agent molecules, but these properties cannot cover all compounds with cooling activity. Since lipophilicity and the formation of hydrogen bonds are the basic elements for producing a cooling sensation, most synthetic cooling agent molecules have such functional groups. Cooling agents can be divided into three categories based on their molecular structures: menthol and its derivatives, amides and other categories.
Menthol and its derivatives
For cooling agents derived directly from menthol, the cooling sensation produced by l-menthol derivatives is significantly stronger than that of d-menthol derivatives. Menthol is on the EFFA list of permitted flavoring ingredients in Europe, and its FEMA number is 2665. Menthol occurs naturally in peppermint, and steam-distilled Asian peppermint oil typically contains 75% l-menthol, compared with only about 50% in regular peppermint oil. Asian mint is the most economical and reliable source of natural mint (it can also be obtained through other varieties of mint). The price of natural menthol often fluctuates, while the synthetic one is relatively stable, but in general the natural one is cheaper.
Menthol is the most widely used traditional cooling agent. Since menthol can produce a cooling sensation on the skin at a dosage of less than 1%, it is particularly commonly used in daily fragrances. The effect of menthol is related to concentration. At low concentrations, it can provide a cooling sensation, while at higher concentrations above 2% to 5%, it will have local anesthesia and irritation. Different from the application of food flavors, the shortcomings of menthol in terms of smell and taste are often not easy to detect in daily flavors. Therefore, menthol is a very valuable cooling agent for daily use, but menthol is used in high concentrations. The irritating effect, especially to the eyes, is still very obvious.
The cooling threshold of menthol in the oral cavity is approximately 0.3 μg, and the cooling activity of l-menthol is 45 times stronger than that of d-menthol. Due to its relatively volatile nature, strong stimulating effect and inherent odor, menthol has limited its application as a cooling agent in food. However, menthol still has high use value in products where mint flavor is acceptable, such as chewing gum, breath fresheners and oral hygiene products. In these applications, menthol is often used with other odorless and longer-lasting cooling agents, such as monomenthol glutarate, which produces a sharper cooling sensation.
(1) Isomers of menthol and cooling agents with related structures
d-(+)-Neo-menthol is the epimer of l-menthol at the hydroxyl position. In the EFFA list of food flavoring ingredients allowed to be used in Europe, the FEMA number is 2666.
(±)-Menthone, in the EFFA list of permitted flavoring ingredients in Europe, FEMA number is 2667.
(1)-Isopulegol (Coolant P), in the EFFA list of food flavoring ingredients allowed to be used in Europe, the FEMA number is 2962. Isopulegol usually produces a cooling sensation, has a minty and grassy aroma, and is a little bitter. However, Takasago Company found that high-purity (1)-isopulementol (>99.7%) is odorless and can be used in lemon flavor. Provides a fresh, cooling sensation. (1)-Isopulegol is sold under the trade name "Coolant P" by Takasago Company.
(2) Menthol derivatives
Menthyl acetate is on the EFFA list of permitted flavoring ingredients in Europe, and its FEMA number is 2668. This compound is occasionally used as a cooling agent. Uses reported in the literature include use in breath fresheners, toothpastes, or with other compounds such as monomenthyl succinate.
Menthyl lactate (Frescolat ML), in the EFFA list of permitted flavoring ingredients in Europe, has a FEMA number of 3748. The compound is classified as a flavorant by FEMA despite its weak minty aroma and earthy taste. It provides a long-lasting cooling sensation in the mouth and is sold under the trade name Frescolat ML by Haarmann & Reimer.
Menthyl glycol carbonate (Frescolat MGC) and menthyl propylene glycol carbonate (Frescolat type MPC), both compounds are on the EFFA list of food flavoring ingredients allowed to be used in Europe, with FEMA numbers 3805 and 3806 respectively. In the EFFA list of food flavoring ingredients allowed for use in Europe, the CAS number of ethylene glycol derivatives is 156679-39-9, and the CAS number of the absolute configuration is l-form is 156324-78-6. The propylene glycol derivative in GRAS is a mixture of 1- and 2-position propylene glycol carbonate. These compounds appear in patent reports and are said to produce a cooling sensation on the skin and oral mucosa but are odorless.
Menthyl 1,2-propanetriol (FrescolatMGA), this compound is on the EFFA list of food flavoring ingredients allowed to be used in Europe, and its FEMA numbers are 3807 and 3808 respectively. Menthone 1,2-glycerol is marketed as Frescolat MGA at Haarmann & Reimer (now Symrise). A large number of literatures have reported its application in food flavor formulations, and in most cases it is used in combination with other cooling agents.
Mono-l-menthol succinate is on the EFFA list of permitted flavoring ingredients in Europe, and its FEMA number is 3810. Although mono-l-menthol succinate has been a known compound for over 100 years, it is still one of the better synthetic cooling agents currently on the market. British American Tobacco first reported its synthesis and application in tobacco in 1962, and in 1965 reported its use as a flavor ingredient in menthol cigarettes to release menthol. The synthesis of this compound is usually relatively simple and can be obtained by reacting menthol with succinic anhydride in a high-pressure or alkaline-catalyzed solution. The compound is odorless, can produce a good cooling sensation, is relatively long-lasting, and is relatively cheap.
Mono-l-(mono)-menthol glutarate (Cooler 2), IFF sells this compound (FEMA 4006) as an analogue of monomenthol succinate under the trade name Cooler 2. Its sensory properties are similar to those of succinate. At the same concentration (25 mg/L, in water), the cooling sensation is about 40 seconds slower, but very long-lasting. It may be the oral cooling agent with the longest lasting cooling sensation on the market. Although this compound has been known for a long time, it has only recently begun to be used in food flavors. Among the same type of cooling agent molecules, glutarate mono-l-(mono)-menthol ester also has a very unique properties, and since the compound is naturally identical, it has significant market advantages in traditional European markets. Other naturally equivalent cooling agents include menthol, menthyl acetate, and menthone, but these cooling agents are relatively short-lasting and often have some unwanted flavor. The earliest synthesis of this compound was in 1928. It was obtained from the alcoholysis of dimenthol ester. Similar to the succinate ester, it can also be easily prepared from the corresponding acid anhydride.
3-(l-menthyl)propyl-1,2-diol (TK-10, Cooling agent 10), this compound is in the EFFA list of food flavoring ingredients allowed to be used in Europe, FEMA number is 3784, in Takasago Company The product name is TK-10. Like other menthol-derived cooling agents, l-form menthol-derived 3-(l-menthol)propyl-1,2-diol has the best cooling sensation. There are patent reports indicating that derivatives of 1-acetyl-2-substituted-3-l-menthenylpropane, isomers of l-menthenyl-2S and 1-acetyl-2-substituted (Hor Ac) derivatives may It has a higher cooling effect, but these have not yet been commercialized. TK-10 is a cooling agent with a strong cooling sensation, and the threshold value in the oral cavity is about 1mg/L. According to reports, although most people consider the compound to be odorless, some still detect it as having some olfactory properties of menthol, some irritation and a bitter taste. At a concentration higher than 50 mg/L, the cooling sensation is long-lasting, but a menthol-like taste can be clearly felt. There are many literature reports on its application in food and daily flavors. Because this compound has a strong cooling sensation and a relatively strong taste, it is more commonly used in daily flavors.
3-(l-menthyl)propyl-1,2-diol has two derivatives with FEMA numbers, one is 3-(l-menthyl)-2-methylpropyl-1,2-diol , FEMA number is 3849, but the market is very small; the other is vanillin 3-(l-menthyl)propyl-1,2-diol, FEMA number is 3904, there are patent reports that it can be used in food flavor formulations middle.
Amides
As mentioned earlier, amide cooling agents can produce a cooling sensation quickly, and some of them have a very long-lasting cooling sensation. The following is the best amide cooling agent currently on the market. Among these amide cooling agents, the most common one on the market is N-ethyl-p-menthyl-3-amide (WS-3). and 2-isopropyl-N,2,3-trimethylbutanamide (WS-23) (WS-3 and WS-23 are registered trademarks of Warner-Lambert Company).
N-ethyl-p-menthyl-3-amide (WS-3), this compound is on the EFFA list of food flavoring ingredients allowed to be used in Europe, and its FEMA number is 3455. WS-3 may be the most important edible cooling agent, with a cooling threshold of about 0.2 mg/L. This compound is basically odorless and has only a weak minty aroma. Compared with menthol, it can produce a cooling sensation quickly and for a longer period of time. This compound was one of the earliest cooling agents discovered by Wilkinson Sword in his pioneering research work in the field of cooling agents. Subsequently, many patents reported its application in various fields. Warner-Lambert Company recently reported its application in food flavor formulations.
Givaudan and Millennium Chemicals now sell this compound. Although the three-dimensional structure is not indicated, the l-form should have the strongest cooling effect. The synthesis route usually involves first converting menthol into menthyl chloride, then preparing the corresponding Grignard reagent, reacting with dry ice, and converting the acid obtained into acid chloride, and then into N-ethyl amide.
2-Isopropyl-N,2,3-trimethylbutanamide (Cooler 3, WS-23), this compound is on the EFFA list of food flavoring ingredients allowed to be used in Europe, and its FEMA number is 3804. 2-Isopropyl The name N,2,3-trimethylbutanamide is somewhat confusing; it is more clearly named N-methyl-2-isopropyl-2,3-dimethylpropionamide. This compound is sold under the trade name WS-23 by some companies and Cooler 3 by IFF. Like WS-3, this compound is also one of the cooling agents developed by Wilkinson Sword. At present, the cooling agent is mainly used in food flavors, such as chewing gum, medicine and breath fresheners. The compound produces a pure cooling sensation without bitterness, burning or irritation. The price of this cooling agent has recently dropped to about $70/kg.
There are many different ways to synthesize WS-23, but the key lies in the synthesis of diisopropylpropylnitrile. Propylonitrile is first alkylated with isopropyl bromide to obtain diisopropylpropylnitrile, which is then hydrolyzed to obtain carboxylic acid and then converted into a methyl-substituted amide.
2-Pyrrolidone-5-carboxylic acid menthyl ester (Questice), which is a cooling agent sold under the trade name Questice by Quest International. Derivatives of proline l-form and d-form are registered, but what is actually sold is a mixture of proline l-form and d-form, both of which are epimeric. body relationship. So far, the product is limited to daily use, but since the compound is an amide derivative of menthol, the skin and oral mucosa are sensitive to it, and it is likely to be used in food flavors.
Other cooling agents
In addition to the cooling agents mentioned above, there are also other cooling agents.
AG-3-5 (Icilin), a derivative of ectoine-2-one, is reported to produce a cooling sensation. As early as 1972, it was reported that when a low dose (<1mg/kg) was injected into the peritoneum of mammals such as mice, the animals would tremble with cold. When the human body is accidentally exposed to the compound, it produces a cooling sensation that lasts about 15 minutes. After 5 to 10 mg of this compound is dissolved in orange juice and taken, a cooling sensation is produced in the mouth, throat, chest cavity and below. A cooling sensation on the inner surface of the cheeks, arms, and legs has also been reported. The compound has been tested to have very low toxicity, with an LD50 of about 1500 mg/kg, but it is suspected to have mutagenic effects. So far there are no reports on the application of this compound. However, this compound has a strong cooling sensation and has great potential application value.
Methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one (3-MPC), 5-methyl-2-(1-pyrrolidinyl)-2-cyclopentene-1 -ketone (5-MPC) and 2,5-dimethyl-4-(1-pyrrolidinyl)-3(2H)-furanone (DMPF), these three compounds are naturally present in malt and are composed of Hofmann and colleagues reported that it can produce a cooling sensation in the mouth and skin surfaces. These compounds were first discovered in the Maillard reaction of glucose and l-proline. Their structures were subsequently confirmed through isolation and chemical synthesis, and they were evaluated by sensory analysis to produce a cooling sensation.
The thresholds of these compounds are 5 to 100 times higher than menthol, but when tasted 50 times higher than the threshold, the cooling sensation is instantaneous, much stronger than menthol, and lasts significantly longer. Although these three compounds all have odors, their thresholds are higher than menthol, so the ratio of cooling threshold/aroma threshold is lower. Therefore, in products that do not require mint flavor, these compounds are better than menthol. Cooling agent selection. It is unclear whether such compounds can be produced on an industrial scale, but they may become very good natural cooling agents for industry.
4-Methyl-3-(pyrrolidinyl)-2(5H)-furanone (4MPF), also naturally found in malt, is more active and is reported to have a cooling sensation in the mouth that is 35 times stronger than menthol. , which is about 500 times stronger on the skin, and the cooling sensation lasts twice as long as menthol.
Mannitol and sorbitol, these two compounds have endothermic phenomena in saliva and therefore produce a cooling sensation. As non-nutritive sweeteners and anti-caking agents, they are widely used in food flavors such as chewing gum and gummies. .
Methyl salicylate, FEMA number 2745, has a typical wintergreen scent and can provide a sweet cooling sensation in some food flavors.
Where to buy cooling agent?
Cooling Agents suppliers and manufacturers-GREEN SPRING®Cooling Agents
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