WO2003097027A1 - OIL-IN-WATER EMULSION OF l-MENTHOL - Google Patents

Abstract

Although an emulsion prepared by emulsifying l-menthol with an emulsifier alone remains stable within several hours after the preparation, l-menthol therein is then gradually separated out and migrates towards the surface. As l-menthol is separated out from the emulsion as described above, the component distribution in the emulsion becomes uneven. When such an emulsion is sprayed as a peristalsis controller onto, for example, the stomach wall, no constant effect can be achieved and, therefore, it is required to prepare the emulsion immediately before using. An oil-in-water emulsion of l-menthol which remains stable without suffering from the separation of l-menthol can be obtained by mixing l-menthol with a fatty acid, a fatty acid ester or a mixture thereof, an emulsifier and water and then emulsifying. When directly sprayed to, for example, the inside of a digestive tract, this emulsion immediately and continuously exhibits its effect of controlling the peristalsis. It can be safely used for a subject under contraindications for the use of scopolamine butyl bromide, for example, a patient with glaucoma.

Description

 Specification

L-menthol oil-in-water emulsion technology

 The present invention relates to separation of L-menthol for a long period after preparation, stable L-menthol oil-in-water emulsion without precipitation and a process for producing the same. Background art

 Gastric peristalsis at the time of gastroscope examination is an obstacle to accurate diagnosis, and it is also a cause of missing minute lesions such as micro cancer.

 Therefore, glucagon, which is an anticholinergic agent, pityl scopolamine (trade name: Buscopane et al.), Has conventionally been used as an anti-perspirant at the time of gastroscope examination. However, butylscopolamine bromide is a contraindication for use in patients with glaucoma, prostate hypertrophy, arrhythmia, etc., and there was a problem that glucagon has a very weak gastric beating inhibitory effect.

 In addition, some of these preparations may cause eye dysregulation, dizziness, etc. The administration of these preparations at the time of endoscopy, for example, for a while, for a while after the examination, There was also a problem that we had to avoid driving.

 On the other hand, it is already known that L-menthol has an effect of suppressing gastric motility, and by administering an emulsion of peppermint oil containing L-menthol as a main component directly to the gastric antrum, it is possible to It is being suppressed

 (GASTROINTESTINAL ENDOSCOPY, Volume 53, No. 2, 17-177 (2001).

However, the content of L and menthol in peppermint oil varies considerably depending on the place of origin of the heat-generating plants and plants, which are the raw material plants, the growing condition, the harvest time, the extraction method, etc. It is not always possible to obtain a certain effect even if a certain amount of it is used as it is as a gastric convulsant. Therefore, it may be possible to use L-menthol emulsion, but the purified L-menthol was emulsified with an emulsifier. By itself, L-menthol separates and precipitates from the emulsion in a relatively short time. Thus, when L-menthol comes out of the emulsion, the components in the emulsion become nonuniform, and even if this constant amount of the emulsion is sprayed on the stomach wall, for example, as a gastric motility control agent, the effect is not constant.

 Therefore, an object of the present invention is to provide a stable L-menthol oil-in-water emulsion which is free from separation and precipitation of L-menthol for a long time after preparation and a process for producing the same. Disclosure of the invention

 The present inventors have conducted various studies to obtain a stable aqueous emulsion of L-menthol, and as a result, L-menthol is emulsified by mixing it with a fatty acid, a fatty acid ester or a mixture thereof, an emulsifier and water. The inventors have found that stable L-in-water oil-in-water emulsions free of L-menthol precipitation for a long time can be obtained, and further studies have been conducted to complete the present invention.

 That is, the present invention

 (1) L-menthol oil-in-water emulsion comprising L-menthol (a), fatty acid, fatty acid ester or mixture thereof (b), and emulsifier (c),

 (2) The L-menthol oil-in-water emulsion according to (1), wherein the fatty acid, fatty acid ester or mixture thereof (b) is liquid at 45 ° C.

 (3) The L-menthol oil-in-water emulsion according to (1), wherein the fatty acid is at least one selected from forelic acid, linoleic acid, linolenic acid and lauric acid.

 (4) L-menthol oil-in-water-type milk according to (1) or (2), wherein the fatty acid ester is at least one selected from glycerine fatty acid ester, polyglycerin fatty acid ester, darikonic acid ester and higher alcohol fatty acid ester Agent,

 (5) An oil-in-water emulsion of L-menthol according to (4), wherein the glycerine fatty acid ester is at least one selected from monodaryceride, diglyceride and triglyceride.

(6) Glycerin fatty acid ester is medium chain triglyceride (MCT), soybean oil, (1) at least one selected from rapeseed oil, safflower oil, corn oil, coconut oil, olive oil, peanut oil, sesame oil and cottonseed oil;

 (7) The L-menthol oil-in-water emulsion according to any one of (1) to (6), wherein the ratio of L-menthol (a) to the whole emulsion is from 0.01 to 5% by weight.

 (8) The L-mentum according to (1) or (2), which contains 0.1 to 100 times by weight a Jf fatty acid, a fatty acid ester or a mixture thereof (b) relative to L-menthol (a) Oil-in-water emulsion,

 (9) The L-menthol oil-in-water emulsion according to any one of (1) to (8), wherein the emulsifier (c) is an edible surfactant.

 (10) The L-menthol oil-in-water emulsion according to (9), wherein the edible surfactant is a nonionic surfactant.

 (11) The L-menthol oil-in-water emulsion according to (10), wherein the edible nonionic surfactant is at least one selected from polyoxyalkylene glycol, sucrose fatty acid ester and solpitanic acid ester;

—L-menthol oil-in-water type emulsion described in (10), which is

 (13) The emulsifier (c) is contained in an amount of 0.1 to 20 times by weight the total weight of L-menthol (a) and Ji fatty acid, fatty acid ester or mixture thereof (b) (1) Or (2) L-menthol oil-in-water emulsion described in L,

 (14) The L-menthol oil-in-water emulsion according to (1) or (2), wherein the L-menthol oil-in-water emulsion has an average particle diameter of 100 nm or more and 500 mm or less;

 (15) A method for producing an L-menthol oil-in-water emulsion, which comprises mixing L-menthol (a) with a fatty acid, fatty acid ester or a mixture thereof (b), an emulsifier (c) and water to emulsify.

L-menthol (a) to be used in the present invention is a pigment obtained by steam-distilling a plant of C. v. Menthapiperita or V. v. Mentha avens is It is the main component of palm oil and is contained in an amount of 30% by weight or more. L-menthol can be obtained from this peppermint oil by fractional distillation or the like with a purity of 90% by weight or more. Recently, it is also manufactured by synthesis. In any case, L-type monosaccharide described in Japanese Pharmacopoeia is preferably used.

 The emulsion of the present invention can be obtained by emulsifying this L-menthol (a) in the presence of a fatty acid, a fatty acid ester or a mixture thereof (b) and an emulsifier (c). The fatty acid, fatty acid ester or mixture thereof (b) should be liquid at 45, preferably 38 ° C.

 Examples of the fatty acid used in the present invention include fatty acids having 8 to 22 carbon atoms such as forelic acid, lauric acid, decanic acid (purinic acid), linoleic acid and linolenic acid, among which lauric acid and the like are particularly preferred. Unsaturated fatty acids such as saturated fatty acid, foreic acid, linoleic acid and linolenic acid are preferred, and foreic acid is particularly preferred.

 Examples of the fatty acid moiety constituting the fatty acid ester used in the present invention include saturated fatty acids having 6 to 22 carbon atoms, such as cabronic acid, catecholic acid, catecholic acid, lauric acid, lauric acid, myristic acid, palmitic acid, stearic acid, etc. And unsaturated fatty acids having 10 to 20 carbon atoms such as forelic acid, linoleic acid, linolenic acid, etc., and alcohol moieties such as ethylene glycol, propylene glycol and polyethylene glycol (minute quantum numbers 40 to 20 0) 0), polypropylene glycol (approximately 500 to 2 0 0 0), glycols such as polydarycol, glycerin such as glycerin and polyglycerin (degree of polymerization 2 to 10), and Examples thereof include sugars such as sucrose and sorbitan or sugar alcohols, and higher alcohols having 16 to 30 carbon atoms.

As fatty acid ester ^ /, for example, monodaryl such as glycol monoborate, diglycolate such as glycol diolate, monodariceride such as glycerin monopalmitate, glycerin monoborate, glycerin dipalmitate, glycerin di Diglycerides such as oleate, triglycerides such as glycerine trilinoleate and glycerine trioleate, polydarylol polyfatty acid esters such as di- to deca-fatty acid esters of di- to decaglycoryl di- to deca-fatty acid esters of di- to decaglycerin, etc. Polyglycerin poly fatty acid ester Etc.

 Vegetable oils, which are mixtures of fatty acid triglycerides, are also suitable examples of fatty acid esters, such as soybean oil, rapeseed oil, safflower oil, corn seed, coconut oil, olive oil, peanut oil, sesame oil, cottonseed oil and medium-chain fatty acid triglycerides. (MCT) etc.

 Examples of the emulsifier (c) used in the present invention include edible nonionic surfactants, ionic surfactants and the like, and preferable ones are polyoxyalkyl glycols such as polyoxyethylene glycol. (Eg average molecular weight 1

Fatty acid esters of sorbitan or sucrose, such as sorbitan monostearate (eg average molecular weight 100 00 to 20 0 0 0 0), propylene glycol (eg average molecular weight 1 0 0 0 0 2 0 0 0 0), etc. And polyoxyethylene sorbitan monolaurate (so-called polysorbate type) and sucrose mono-ate.

 Any known method can be used to prepare the emulsion. One of the preferred methods is as follows.

 First, L-menthol is mixed with, preferably dissolved in, a fatty acid, fatty acid ester or a mixture thereof. The mixing and dissolution may be carried out at room temperature or under heating, preferably at 40 to 55 ° C. An emulsifier is added to the obtained homogeneous mixture of L-menthol and fatty acid or fatty acid ester, or a mixture thereof, and the mixture is thoroughly stirred using a stirrer such as a homomixer. A necessary amount of water is added to the solution, the solution is further stirred, and if necessary, ultrasonication is further carried out, or a high pressure emulsifier is used to make the grains in the emulsion as homogeneous as possible. The average grain size of the emulsion thus obtained is usually from 100 nm to 500 nm, preferably from 105 nm to 300 nm.

 The proportions of each component used in preparation of the emulsion are as follows.

 The proportion of L-menthol used in the emulsion is 0.01 to 5% by weight, preferably 0.1 to 5% by weight, and more preferably 0.5 to 3% by weight.

The ratio of fatty acid or fatty acid ester to menthol is 0.1 to 100 Weight times, preferably 0.1 to 20 times weight

 The ratio of the emulsifier (c) to the total weight of L) menthol) and fatty acid, fatty acid ester or mixture (b) is 0.01 to 2.0 times by weight, preferably 0.0 to 1.0 times by weight It is.

 Furthermore, if necessary, thickeners, stabilizers, preservatives, antifoaming agents and the like can be added as appropriate.

 As the thickener, carrageenan, methylcellulose (MC), carboxmethyl cellulose (CMC), guar gum, pectin, etc. may be mentioned. By adding these thickeners, it is possible to adjust the drooping rate when the emulsion is sprayed inside the digestive tract to an appropriate one. Although the addition amount of a thickener changes with kinds of thickener, it is normally selected in 0.01 to 5 weight%.

 Examples of the stabilizer include sodium edetate and the like. Examples of the preservative include sorbic acid, benzalconium chloride, paraben and the like, and examples of the antifoamer include silicone oils such as dimethylpolysiloxane xylophane. The appropriate amount of each can be added.

 The L-menthol oil-in-water emulsion of the present invention has an effect of appropriately suppressing its peristalsis by being directly applied to smooth muscle. Therefore, as an application site of the smooth muscle anti-beating agent comprising the L-menthol oil-in-water emulsion of the present invention, for example, gastrointestinal smooth muscle such as esophagus, stomach, duodenum, bile duct, small intestine, large intestine, colon, rectum etc. can be mentioned. . For example, at the time of digestive tract surgery or surgery with an endoscope, at the time of endoscopic examination of the digestive tract with an endoscope, or in other medical procedures where it is necessary to suppress digestive tract movements, this agent may be used as a sprayer or an endoscope forceps hole etc. Spray it directly into the digestive tract or fill the digestive tract such as the stomach or intestine through a tube etc., and let the emulsion contact smooth muscle. In the case of direct administration of a fixed amount of emulsion from a sprayer or a forceps hole of an endoscope tip, it is preferable to fill the prepared emulsion in a extrudable container such as a prefill syringe or the like. Of course, the emulsion of the present invention can also be stored in containers such as vials and ampoules. Brief description of the drawings

Fig. 1 shows the results of L 一 1 against carbachol-stimulated contraction of smooth muscle of Mormococcygeum ileum. It is a graph which shows the effect of menthol. BEST MODE FOR CARRYING OUT THE INVENTION

 The present invention will be specifically described by way of examples, comparative examples and test examples.

Example 1

 L-Men! ^ G of monohydroxide was mixed with 0.5 g of oleic acid and dissolved in a water bath at 50 ° C. Then, 0.2 g of sucrose fatty acid ester (Surf Hope; 1-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 5 OmL of water were added, and the mixture was emulsified with a homomixer (manufactured by POLYTRON PT1000 KINEMATICA). Water was added to make the total volume 140 mL, and emulsification was carried out with an ultrasonic emulsifier (manufactured by SONIFIER 250 BRANSON) at 50 ° C. for 30 minutes to obtain an emulsion. The average particle size of the emulsion was 165. Onm as a result of measurement by a particle size measuring apparatus (manufactured by Otsuka Electronics Co., Ltd.).

Comparative example 1

 0.2 g of sucrose fatty acid ester (made by SAIF HOPE 1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 10 OmL of water were added to 1 g of L-menthol and emulsified in a 50 ° C. water bath with a homomixer. Water was added to make the total amount 14 OmL, and ultrasonic emulsification was carried out at 50 ° C for 10 minutes to obtain an emulsion. The average particle size of the emulsion was 188.5 nm.

Comparative example 2

 1 g of L-menthol and 5.O g of propylene glycol were mixed and dissolved in a water bath at 50 ° C. Next, 0. 1 g of sucrose fatty acid ester (Surfhope; K-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) was added, and the mixture was emulsified with a homomixer. Water was added to bring the total volume to 14 OmL, and emulsification was carried out with an ultrasonic emulsifying machine at 50 ° (: 10 minutes) to obtain an emulsion. The average particle size of the emulsion was measured with a particle size measuring device. Example 2

L-Men! 1 g of L, 0.4 g of foreic acid and 0.1 g of stearic acid were mixed and dissolved in a water bath of 5. Next, 0.5 g of sucrose fatty acid ester (Safe Hope J-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 10 OmL of water were added, and the mixture was emulsified with a homomixer. Water was added to make the total volume 14 OmL, and ultrasonic emulsification was carried out at 50 ° C. for 10 minutes to obtain an emulsion. The average particle size of the emulsion was 111.2 nm. Example 3

 1 g of L-menthol, 0.25 g of oleic acid and 0.25 g of lauric acid were mixed and dissolved in a water bath at 50 ° C. Next, 0.5 g of sucrose fatty acid ester (Surf Hope J-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 10 OmL of water were added and the mixture was emulsified with a homomixer. Water was added to bring the total volume to 14OmL, and ultrasonication was carried out at 50 ° (: 10 minutes) to obtain an emulsion. The average particle size of the emulsion was 107.4 nm.

Example 4

 1 g of L-men and 4.0 g of soybean oil were mixed and dissolved in a 50 ° C. water bath. Next, 0.5 g of sucrose fatty acid ester (Saif Hophe J-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 5 OmL of water were added, and the mixture was emulsified with a homomixer. Water was added to make the total volume 14 OmL, and ultrasonic emulsification was carried out for 50, 10 minutes to obtain an emulsion. The average particle size of the emulsion was 219.3 nm.

Example 5

 1 g of L-menthol and 2.0 g of MCT (Panacet 800J manufactured by Nippon Oil and Fats Co., Ltd.) were mixed and dissolved in a 50 ° C. water bath. Next, 0.3 g of sucrose fatty acid ester (Serf Hope; [-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 5 OmL of water were added, and the mixture was emulsified with a homomixer. Water was added to make the total amount 14 OmL, and ultrasonic emulsification was performed at 50 ° C for 10 minutes to obtain an emulsion. The average particle size of the emulsion was 207.3 nm. Example 6

 1 g of L-menthol was mixed with 0.25 g of lauric acid and dissolved in a 50 ° C. water bath. Next, 0.2 g of sucrose fat J3 ester (Sauphope J-1816, manufactured by Mitsubishi Chemical Foods & Co., Ltd.) and 10.O mL of water were added, and the mixture was emulsified with a homomixer. Water was added to make the total volume 140 mL, and ultrasonic emulsification was carried out at 50 ° C. for 10 minutes to obtain an emulsion. The average particle size of the emulsion was 199 nm.

Example 7

1 g of L menthol was mixed with 0.75 g of propylene glycol fatty acid ester (Rikemar P0-100 manufactured by Riken Vitamin Co., Ltd.) and dissolved in a 50 ° C. water bath. Next, 0.5 g of sucrose fatty acid ester (Surfhope;-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 10 OmL of water were added, and the mixture was emulsified with a homomixer. Add water to the whole The emulsion was adjusted to 140 mL and subjected to ultrasonic emulsification for 50 minutes and 10 minutes to obtain an emulsion. The average particle size of the emulsion was 125. Onm.

Example 8

 1 g of L-menthol was mixed with 0.75 g of propylene glycol monoborate and dissolved in a 50 water bath. Next, Polysorbate—80

T-80 PA (manufactured by Sanyo Chemical Industries, Ltd.) 0.25 g and 10 OmL of water were added, and the mixture was emulsified with a homomixer. Water was added to make the total volume 14 OmL, and ultrasonic emulsification was carried out for 50, 10 minutes to obtain an emulsion. The average particle size of the emulsion was 186.7 nm.

Example 9

 1 g of L-menthol was mixed with 0.75 g of propylene glycol monoborate and dissolved in a 50 ° C. water bath. Subsequently, 0.25 g of sucrose fatty acid ester (Surfhope J-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 10 OmL of water were added, and the mixture was emulsified with a homomixer. Water was added to make the total amount 14 OmL, and ultrasonic emulsification was carried out at 50 ° C for 10 minutes to obtain an emulsion. The average particle size of the emulsion was 161.6 nm.

Example 10

 One gram of L menthol and 4.O g of olive oil were mixed and dissolved in a water bath at 50 ° C. Subsequently, 0.5 g of sucrose fatty acid ester (Surfhope; 1-1816, manufactured by Mitsubishi Chemical Foods Co., Ltd.) and 10 OmL of water were added, and the mixture was emulsified with a homomixer. Water was added to make the total volume 140 mL, and ultrasonic emulsification was carried out at 50 ° C. for 10 minutes to obtain an emulsion. The average particle size of the emulsion was 218.2 nm.

Test example 1

20 ml each of the emulsions obtained in Examples 1 to 10 and Comparative Examples 1 and 2 are put in a 20 ml vial, sealed, and allowed to stand at room temperature (average 25 ° C.), immediately after preparation for 48 hours. The stability of the emulsion was observed visually throughout. The results are shown in Table 1. 【table 1】

○: No floating oil droplets.

 Δ: Floating oil droplets are faintly observed.

 X: Floating oil droplets are clearly observed.

 As is clear from the results in Table 1, it was confirmed that the examples of the present invention are superior in storage stability to the comparative examples.

Test example 2

 Effects of L-menthol on carbachol-stimulated contraction of guinea pig isolated ileal smooth muscle

 Test material and method

 Animal Har 1 1 ey male guinea pig (6-: L 0 weeks old)

 Drug Use Nourishing solution (Tyrode solution)

Extraction and preparation of tissue samples The head of Mormogu, which had been fasted for 17 to 24 hours, was beaten and killed by bleeding from the carotid artery, and the laparotomy was exposed to expose the ileum. The ileum was removed about 15 cm from about 1 O cm away from the cecum and immersed in a nutrient solution to remove the contents. An ileal specimen of about 2 cm in length was prepared and used for the experiment.

 Fixation to the Magnus device

The excised tissue samples were self-inserted and suspended under a load of 0.5-1.5 g on an isometric transducer. After that, it was suspended for 30 minutes or more to stabilize, and drug treatment was started. Pre Magnus tube is warmed to 2 8 ° C in a state filled with Tyrode solution of 2 O mL, was air with 95% C_〇 ₂ Z 5% 0 ₂ mixed gas.

 Drug treatment

 The isolated ileal smooth muscle was treated with the L-menthol emulsion prepared in Example 1 and the solvent prepared in the same manner as in Example 1 except that L-menthol was not formulated, and after 5 minutes, rubalylcholine chloride (carbacol) was Treatment was carried out stepwise from low concentration. In addition, when the contraction response of smooth muscle decreased from the maximum peak, force rubacor was treated promptly, and the treatment was ended when the contraction response did not increase. L-menthol was treated to a final concentration of 86.0 mg / L. We also performed negative controls (no treatment).

 Result

 As apparent from FIG. 1, the L-menthol emulsion (dotted line) of the present invention clearly suppressed the stimulation contraction of calpacoll. At that time, the solvent (dotted line) was almost the same as no treatment (solid line) and did not affect the contraction. Industrial applicability

 Since the L-menthol emulsion of the present invention is stable after the preparation of the emulsion, it is not necessary to prepare it at the time of use. The suppression effect is exhibited and the effect lasts for a long time. Furthermore, it has the advantage of being able to be used without any problems for patients with glaucoma, prostatic hypertrophy, arrhythmia patients, etc. whose use is prohibited like Buscopan, so it is safe and easy. Peristalsis of the digestive tract can be suppressed.

Claims

The scope of the claims 1. L-menthol oil-in-water emulsion comprising 'L-menthol (a), fatty acid, fatty acid ester or mixture thereof (b) and emulsifier (c).  2. The L-menthol oil-in-water emulsion according to claim 1, wherein the fatty acid, fatty acid ester or mixture thereof (b) is 45 and liquid.  3. The L-menthol oil-in-water emulsion according to claim 1, wherein the fatty acid is at least one selected from foreic acid, linoleic acid, linolenic acid and lauric acid.  4. The L-menthol oil-in-water emulsion according to claim 1 or 2, wherein the fatty acid ester is at least one selected from glycerin fatty acid ester, polyglycerin fatty acid ester, daryl fatty acid ester and higher alcohol fatty acid ester.  5. The oil-in-water emulsion of L-menthol according to claim 4, wherein the glycerin fatty acid ester is at least one selected from monodarylide, diglyceride and triglyceride.  6. The glycerin fatty acid ester is at least one selected from medium chain triglyceride (MCT), soybean oil, rapeseed oil, safflower oil, corn oil, coconut oil, olive oil, olive oil, peanut oil, sesame oil and cottonseed oil. L-menthol oil-in-water emulsion described in 4;  7. The L_menthol oil-in-water emulsion according to any one of claims 1 to 6, wherein the ratio of L 1 menthol (a) to the whole emulsion is 0.01 to 5% by weight.  8. The L-menthol oil-in-water emulsion according to claim 1 or 2, wherein the fatty acid, fatty acid ester or mixture thereof (b) is contained in an amount of 0.1 to 100 times by weight with respect to L-menthol (a).  9. The L-menthol oil-in-water emulsion according to any one of claims 1 to 8, wherein the emulsifier (c) is an edible surfactant.  10. The L-menthol oil-in-water emulsion according to claim 9, wherein the edible surfactant is a nonionic surfactant. 11. Edible non-ionic surfactant is polyoxyalkylene glycol, sucrose 11. The L-menthol oil-in-water emulsion according to claim 10, which is at least one selected from fatty acid esters and sorbitan fatty acid esters.  12. The L-menthol oil-in-water emulsion according to claim 10, wherein the nonionic surfactant is polyoxyethylene polyoxypropylene glycol or polysorbate 80.  13. The method according to claim 1 or 2, wherein the emulsifier (c) is contained in an amount of 0.1 to 20 times by weight the total weight of L-menthol (a) and fatty acid, fatty acid ester or mixture thereof (b). L-menthol oil-in-water emulsion.  14. The L-menthol oil-in-water emulsion according to claim 1 or 2, wherein the L-menthol oil-in-water emulsion has an average particle diameter of 100 nm or more and 500 nm or less.  15. A method for producing an L-menthol oil-in-water emulsion, which comprises mixing L_menthol (a) with a fatty acid, fatty acid ester or a mixture thereof (b), an emulsifier (c) and water to emulsify.