JPH10298109A - Preservative for emulsion and emulsion - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an emulsion having excellent storage stability and less adverse effects, since the subjective preservative imparts its excellent preservative efficacy even to 0/W type emulsion at its low concentration. SOLUTION: This preservative for emulsion comprises sorbic acid or a pharmaceutically acceptable salt thereof, and as needed, disodium edetate and boric acid. The other objective emulsion comprises sorbic acid or a pharmaceutically acceptable salt thereof, and as needed, disodium edetate and boric acid as well as the major drug. The storage method for the emulsion comprises compounding the emulsion with sorbic acid or a pharmaceutically acceptable salt thereof, and as needed, disodium edetate and boric acid at their respective pharmaceutically acceptable concentrations effective for storage of the emulsion.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a preservative for an emulsion containing sorbic acid or a pharmaceutically acceptable salt thereof, which provides excellent preservative efficacy at a low concentration, and contains the compound or the compound. The present invention relates to an emulsion that can be safely administered to humans, containing an emulsion preservative together with a base drug. Also,
The present invention relates to a method for preserving an emulsion, which comprises incorporating sorbic acid or a pharmaceutically acceptable salt thereof into the emulsion.

[0002]

2. Description of the Related Art When formulating eye drops, nasal drops and ear drops, a preservative is incorporated for the purpose of preventing secondary contamination by microorganisms present in the air, tears, nasal passages, ear canals, and the like. I do. The same applies to emulsions. Conventionally, when a drug is formulated into an emulsion, for example, a paraoxybenzoate, benzalkonium chloride or the like is blended as a preservative. However, when formulated into an emulsion, particularly an oil-in-water (O / W) emulsion, there is a problem that these conventional preservatives cannot provide a sufficient preservative effect. Also, p of the dispersion medium
When H is relatively high, the preservation effect is further attenuated because the microorganisms are easy to propagate. However, if the amount of the preservative is increased in order to enhance the preservability of the drug, side effects due to a high concentration of the preservative, such as increased irritation to the living body, may be caused.

[0003] As described above, when a drug is formulated into an emulsion, it is necessary to mix a preservative at a high concentration in order to obtain high preservability. There is a dilemma that the blending amount must be limited. Therefore, development of a preservative which gives an excellent preservation effect to an emulsion at a low concentration is desired.

[0004]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an emulsion, particularly an oil-in-water (O / W) emulsion, at a low concentration.
In particular, it is an object of the present invention to provide a compound capable of giving an excellent preservative effect to an oil-in-water emulsion having a high pH of a dispersion medium, and a preservative for emulsion containing the compound. Another object of the present invention is to provide an emulsion containing the compound or the preservative, which has excellent preservability and can be safely administered to humans, especially an ophthalmic, nasal or ear emulsion. It is.

[0005]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, when sorbic acid or a pharmaceutically acceptable salt thereof is added to the emulsion,
It has been found that an excellent preservative effect can be imparted to an emulsion even at a low concentration. Further, the present inventors
When the pH of the emulsion is high, if sodium edetate and boric acid are further added in addition to sorbic acid or a pharmaceutically acceptable salt thereof, better preservability can be obtained in the emulsion even at a low concentration. And completed the present invention.

That is, the present invention relates to a preservative for an emulsion containing sorbic acid or a pharmaceutically acceptable salt thereof, particularly 0.001 to 5 (W / V)%, preferably 0.01 to 5%, of the compound.
This is a preservative for an emulsion containing 1 (W / V)%. The present invention also relates to any one of the above emulsion preservatives containing sodium edetate and boric acid in addition to the compound, in particular, sodium edetate of 0.001 to 0.001.
0.2 (W / V)%, especially sodium edetate 0.0
0.05-0.1 (W / V)% and boric acid in 0.001
The emulsion preservative according to any one of the above, which is contained at a concentration of from 10 to 10 (W / V)%, particularly 0.01 to 5 (W / V)%.
Further, the present invention is any of the above preservatives for an emulsion having an ophthalmic, nasal or otic dosage form. Also,
Another invention relates to an emulsion containing sorbic acid or a pharmaceutically acceptable salt thereof, or a preservative for an emulsion containing the compound together with the active ingredient and a pharmaceutically acceptable carrier, particularly, sorbic acid or a pharmaceutically acceptable salt thereof. 0.0
01-5 (W / V)%, especially 0.01-1 (W / V)%
Is the above emulsion. The present invention also relates to an emulsion containing sorbic acid or a pharmaceutically acceptable salt thereof, sodium edetate and boric acid together with a main drug and a pharmaceutically acceptable carrier, or sorbic acid or a pharmaceutically acceptable salt thereof. Further, an emulsion containing a preservative for emulsion containing sodium edetate and boric acid together with the main drug and a pharmaceutically acceptable carrier, particularly, sorbic acid or a pharmaceutically acceptable salt thereof, in an amount of 0.001 to 5
(W / V)%, especially 0.01 to 1 (W / V)%, sodium edetate 0.001 to 0.2 (W / V)%, especially 0.005 to 0.1 (W / V)%, and boric acid in 0.1%.
001-10 (W / V)%, especially 0.01-5 (W / V)
V) The above emulsion containing at a concentration of%. Further, the present invention is any of the above emulsions having an ophthalmic, nasal or ear drop dosage form. The present invention relates to a method for preserving an emulsion, which comprises incorporating sorbic acid or a pharmaceutically acceptable salt thereof into an emulsion in a concentration effective for preserving the emulsion and at a pharmaceutically acceptable concentration, particularly sorbic acid or a pharmaceutically acceptable salt thereof. 0.001 to 5 (W / V)%, preferably 0.01 to 1
(W / V)%. The present invention also provides sorbic acid or a pharmaceutically acceptable salt thereof, sodium edetate and boric acid,
An emulsion preservation method comprising blending the emulsion at a concentration that is effective for preserving the emulsion and at a pharmaceutically acceptable concentration, in particular, using sorbic acid or a pharmaceutically acceptable salt thereof in an amount of 0.001 to 5 (W
/ E), especially 0.01-1 (W / V)%, and sodium edetate 0.001-0.2 (W / V)%, especially 0.1%.
005-0.1 (W / V)% and boric acid in 0.00
1 to 10 (W / V)%, especially 0.01 to 5 (W / V)%
The method according to the above, characterized in that the compound is blended at a concentration of: The present invention also relates to the method for preserving any of the above emulsions, wherein the emulsion has a dosage form for eye drops, nasal drops or ear drops.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The preservative for an emulsion of the present invention contains sorbic acid or a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts of sorbic acid that can be used in the present invention include, for example, salts of alkali metals such as sodium and potassium, and salts of alkaline earth metals such as calcium and magnesium.

When the preservative for an emulsion of the present invention is incorporated into an emulsion having a pH of 6.0 or more, the preservative for an emulsion further contains sodium edetate and boric acid in addition to sorbic acid or a pharmaceutically acceptable salt thereof. Is preferred.

The concentration of sorbic acid or a pharmaceutically acceptable salt thereof in the emulsion preservative of the present invention is 0.00
1 to 5 (W / V)%, preferably 0.01 to 1 (W / V)
V)%. When sodium edetate and boric acid are further contained, the concentration of sodium edetate is 0.001 to 0.2 (W / V)%, preferably 0.02%.
And the concentration of boric acid is 0.001 to 10.0 (W / V)%, preferably 0.0 to 0.1 (W / V)%.
1 to 5.0 (W / V)%.

The preservatives for the emulsion of the present invention include, in addition to sorbic acid or a pharmaceutically acceptable salt thereof, emulsifiers such as polysorbate 80 and polyoxyethylene hydrogenated castor oil 60, sodium acetate, monohydrogen phosphate and the like. Buffers such as disodium and tonicity agents such as sodium chloride and glycerin can be added.

The preservative for the emulsion of the present invention may be prepared by a known method. For example, sorbic acid or a pharmaceutically acceptable salt thereof is dissolved in sterile purified water or an aqueous solvent. This solution can be prepared by further dissolving sodium edetate and boric acid as needed, and further blending the above-mentioned additives as needed.

The preservative for an emulsion of the present invention is not particularly limited as long as it is an emulsion and can be blended with any emulsion. When used in an oil-in-water (O / W) emulsion, the preservative becomes a dispersion medium, and when used in a water-in-oil (W / O) emulsion, the preservative becomes a dispersed phase.

The emulsion preservative of the present invention is an oil-in-water type (O
/ W) emulsions and other types of emulsions can provide excellent storage efficacy even at low blending concentrations. Therefore, by incorporating the preservative for emulsion of the present invention into the emulsion, it is possible to provide an emulsion having a high preservability and a very low side effect of the preservative due to a low concentration of the preservative.

The use of the emulsion of the present invention is not particularly limited as long as it contains sorbic acid or a pharmaceutically acceptable salt thereof, or the above-mentioned preservative for an emulsion, together with the active ingredient. It is an emulsion. There is no particular limitation on the drug used as the main drug, and various drugs such as steroidal anti-inflammatory drugs, non-steroidal anti-inflammatory drugs, antibiotics, antiviral agents, fat-soluble vitamins, and combinations thereof are exemplified.

The concentration of sorbic acid or a pharmaceutically acceptable salt thereof in the emulsion of the present invention is 0.001 to 5
(W / V)%, preferably 0.01 to 1 (W / V)%. When sodium edetate and boric acid are further contained, the concentration of sodium edetate is 0.0%.
01-0.2 (W / V)%, preferably 0.005-
0.1 (W / V)%, and the content of boric acid is 0.0
01 to 10.0 (W / V)%, preferably 0.01 to
5.0 (W / V)%.

In the emulsion of the present invention, the content of the drug serving as the main drug varies depending on the type of each drug. For example, in the case of the emulsion of the present invention containing a steroidal anti-inflammatory drug as an active ingredient, the content is 0.1%. It is about 001 to 5 (W / V)%, preferably about 0.005 to 1 (W / V)%, and more preferably about 0.01 to 0.5 (W / V)%.

The type of oil contained in the emulsion of the present invention is preferably one having low toxicity and low irritation, especially one applicable to the eyes, nose, ears and the like. Castor oil, peanut oil, cottonseed oil, soybean oil, olive oil, medium chain fatty acid triglycerides, oleic acid and the like.

The emulsion of the present invention may contain a nonionic surfactant as an emulsifier in order to enhance emulsion stability. Examples of nonionic surfactants include polyoxyethylene sorbitan fatty acid esters (eg, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, etc.). Polyoxyethylene hydrogenated castor oil 60, sorbitan fatty acid esters (eg, sorbitan monooleate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, etc.),
Examples thereof include polyoxyethylene alkyl ether (for example, polyoxyethylene lauryl ether) and polyoxyethylene fatty acid ester (for example, polyoxyethylene monostearate).

The emulsion of the present invention may contain a buffer. Examples of the buffer include acetates such as sodium acetate, monosodium dihydrogen phosphate, disodium monohydrogen phosphate, monopotassium dihydrogen phosphate, phosphates such as dipotassium monohydrogen phosphate, and epsilon aminocaproic acid. And amino acids such as sodium glutamate, boric acid and its salts, citric acid and its salts, and the like.

The emulsion of the present invention may contain a tonicity agent. Examples of isotonic agents include sodium chloride, glycerin, glucose, mannitol, sorbitol and the like.

The emulsion of the present invention may further contain various additives such as a stabilizer, an antioxidant, a chelating agent, a pH adjuster, and a thickener. Examples of antioxidants include ascorbic acid and its salts, tocopherol, sodium thiosulfate, sodium bisulfite, pyruvic acid and its salts, and the like. Examples of chelating agents include sodium edetate, citric acid and salts thereof. p
Examples of the H adjustor include hydrochloric acid, phosphoric acid, acetic acid, sulfuric acid, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, and aqueous ammonia. The pH of the emulsion of the present invention is preferably from 2.5 to 8.5.

The median diameter of the dispersed phase particles in the emulsion of the present invention is preferably from 5 to 0.0001 μm, more preferably from 1 to 0.001 μm. The emulsion of the present invention can be prepared by a known method. That is, sorbic acid or a pharmaceutically acceptable salt thereof, and, if necessary, sodium edetate and boric acid, and if the main drug is water-soluble, further dissolve the main drug in water or an aqueous solvent to form an aqueous phase, It is prepared by emulsifying an aqueous phase and a separately prepared oil phase (in which the main drug is dissolved if the main drug is fat-soluble). If necessary, further emulsifiers and other additives can be added to the water phase and / or the oil phase.

More specifically, for example, in the case of an oil-in-water emulsion, sorbic acid or a pharmaceutically acceptable salt thereof, and, if necessary, further sodium edetate and boric acid; It can be prepared by adding the above additives and emulsifiers, adjusting the pH to 2.5 to 8.5 using a pH adjuster, and then adding an oil in which a drug serving as a main drug is dissolved to form an emulsion. it can. In order to perform uniform emulsification, known means such as a mixer, a homogenizer, a microfluidizer, and a high-pressure homogenizer can be used.

Alternatively, the emulsion of the present invention is an emulsion containing a preservative for the emulsion of the present invention prepared in advance, ie, sorbic acid or a pharmaceutically acceptable salt thereof, and, if necessary, sodium edetate and boric acid. In the preservative, emulsifiers and other additives, if necessary, and if the active ingredient is water-soluble, dissolve the active ingredient to form an aqueous phase, and separately from this, separate the emulsifier and other additives as needed in oil. In the case where the substance or the main drug is fat-soluble, it can also be prepared by dissolving the main drug into an oil phase, and emulsifying the aqueous phase and the oil phase using known means.

The emulsion of the present invention is preferably used as an emulsion for topical administration to the eyes, nose or ears, and is further preferably formulated into ophthalmic, nasal or ear drops for use.

The emulsion of the present invention has a high preservability because it contains a preservative exhibiting excellent preservative effect even at a low concentration.
Further, since the concentration of the preservative is low, side effects due to the preservative are extremely small.

[0027]

The present invention will be described in more detail with reference to the following examples and test examples, but the present invention is not limited to these examples.

Example 1 Castor oil 5.0 g polysorbate 80 4.0 g concentrated glycerin 2.6 g sodium acetate 0.01 g sorbic acid 0.1 g sodium hydroxide appropriate amount in 100 mL sterile purified water appropriate amount (pH 5.0) Heated to about 70 ° C, polysorbate 80,
Concentrated glycerin, sodium acetate and sorbic acid were added and dissolved, and the pH was adjusted to 5.0 with sodium hydroxide. While stirring this liquid with a homomixer, castor oil heated to about 70 ° C. was added to obtain a crude emulsion. This coarse emulsion was treated with a microfluidizer to further disperse the dispersed phase particles, and sterilized by filtration to obtain an emulsion.

Example 2 100,000 I.L. of retinol palmitate in 100 mL U. Castor oil 5.0 g Polysorbate 80 4.0 g Concentrated glycerin 2.0 g Sodium acetate 0.01 g Boric acid 0.5 g Sorbic acid 0.1 g Sodium edetate 0.05 g Sodium hydroxide Appropriate amount Sterilized purified water Appropriate amount (pH 6.0) Sterilization Heat the purified water to about 70 ° C. and use polysorbate 80,
Concentrated glycerin, sodium acetate, sorbic acid, boric acid and sodium edetate were added and dissolved, and the pH was adjusted to 6.0 with sodium hydroxide to obtain an aqueous phase. Separately, castor oil was heated to about 70 ° C., and retinol palmitate was added and dissolved to obtain an oil phase. The aqueous phase heated to about 70 ° C. was heated (about 70 ° C.) while stirring with a homomixer, and the oil phase was added to obtain a crude emulsion. This coarse emulsion was treated with a microfluidizer to further disperse the dispersed phase particles, and sterilized by filtration to obtain an emulsion.

Example 3 Tocopherol acetate 0.01 g in 100 mL Castor oil 5.0 g Polysorbate 80 4.0 g Concentrated glycerin 2.2 g Epsilon aminocaproic acid 0.05 g Sorbic acid 0.2 g Hydrochloric acid Appropriate amount Sterilized purified water Appropriate amount (pH 5.0) Sterile purified water is heated to about 70 ° C., and polysorbate 80,
Concentrated glycerin, epsilon aminocaproic acid and sorbic acid were added and dissolved, and the pH was adjusted to 5.0 with hydrochloric acid to obtain an aqueous phase. Separately, castor oil was heated to about 70 ° C., and tocopherol acetate was added and dissolved to obtain an oil phase. The aqueous phase heated to about 70 ° C. was heated (about 70 ° C.) while stirring with a homomixer, and the oil phase was added to obtain a crude emulsion. This coarse emulsion was treated with a microfluidizer to further disperse the dispersed phase particles, and sterilized by filtration to obtain an emulsion.

Example 4 Pyrenoxine 0.005 g castor oil 5.0 g polysorbate 80 4.0 g concentrated glycerin 2.6 g sodium acetate 0.01 g boric acid 0.1 g sorbic acid 0.1 g sodium edetate 0.05 g hydroxide in 100 mL Sodium qs Sterile purified water qs (pH 3.0) Sterile purified water is heated to about 70 ° C and polysorbate 80
Concentrated glycerin, sodium acetate, sorbic acid, boric acid and sodium edetate were added and dissolved, and the pH was adjusted to 3.0 with sodium hydroxide to obtain an aqueous phase. Separately, castor oil was heated to about 70 ° C., and pinorexin was added and dissolved to obtain an oil phase. The aqueous phase heated to about 70 ° C. was heated (about 70 ° C.) while stirring with a homomixer, and the oil phase was added to obtain a crude emulsion. This coarse emulsion was treated with a microfluidizer to further disperse the dispersed phase particles, and sterilized by filtration to obtain an emulsion.

Comparative Example 1 Castor oil 5.0 g polysorbate 80 4.0 g concentrated glycerin 2.6 g sodium acetate 0.01 g benzalkonium chloride 0.005 g hydrochloric acid qs sterile purified water qs in 100 mL instead of sorbic acid in 100 mL Was prepared in the same manner as in Example 1 except that benzalkonium chloride was used and pH was adjusted with hydrochloric acid instead of sodium hydroxide.

Comparative Example 2 Castor oil 5.0 g polysorbate 80 4.0 g concentrated glycerin 2.6 g sodium acetate 0.01 g chlorhexidine gluconate 0.005 g hydrochloric acid qs sterile purified water qs in 100 ml instead of sorbic acid in 100 ml An emulsion having the above formulation was obtained in the same manner as in Example 1 except that chlorhexidine gluconate was used and the pH was adjusted with hydrochloric acid instead of sodium hydroxide.

Comparative Example 3 Castor oil 5.0 g polysorbate 80 4.0 g concentrated glycerin 2.6 g sodium acetate 0.01 g methyl parahydroxybenzoate 0.026 g propyl paraoxybenzoate 0.014 g hydrochloric acid qs sterile purified water qs in 100 mL 0.0) An emulsion having the above formulation was obtained in the same manner as in Example 1 except that methyl paraoxybenzoate and propyl paraoxybenzoate were used instead of sorbic acid, and the pH was adjusted with hydrochloric acid instead of sodium hydroxide. .

Test Example 1 Storage Efficacy Test (1) A preservation efficiency test was performed on the emulsions of the formulations of Example 1 and Comparative Examples 1 to 3 in accordance with the thirteenth revised Japanese Pharmacopoeia. The results are shown in Tables 1 to 4.

[0036]

[Table 1]

[0037]

[Table 2]

[0038]

[Table 3]

[0039]

[Table 4]

From the above results, it was found that only the emulsion of the formulation of Example 1 containing sorbic acid killed bacteria in the second week and did not show any growth of fungi. It has been shown to have a preservative efficacy.

Example 5 Castor oil 5.0 g polysorbate 80 4.0 g concentrated glycerin 2.2 g sodium acetate 0.05 g boric acid 0.1 g sorbic acid 0.1 g sodium edetate 0.02 g sodium hydroxide in 100 ml 100 ml sterile purification Suitable amount of water (pH 6.0) An emulsion of the above formulation was obtained in the same manner as in Example 1 except that sodium edetate and boric acid were added in addition to sorbic acid.

Test Example 2 Storage Efficacy Test (2) A storage efficiency test was conducted on the emulsion of the formulation of Example 5 in the same manner as in Test Example 1. Table 5 shows the results.

[0043]

[Table 5]

As can be seen from Table 5, at pH 6.0, the emulsion of the formulation of Example 5 containing sorbic acid, boric acid and sodium edetate kills bacteria and increases fungal growth in the second week. It was not recognized, and was compatible with the Japanese Pharmacopoeia, indicating that it had excellent preservative efficacy.

Example 6 Medium-chain fatty acid triglyceride in 100 mL 5.0 g Polysorbate 80 4.0 g Concentrated glycerin 2.6 g Sodium acetate 0.05 g Sorbic acid 0.1 g Sodium hydroxide qs Sterile purified water qs (pH 5.0) Castor oil Was prepared in the same manner as in Example 1 except that a medium-chain fatty acid triglyceride was used in place of the above.

Comparative Example 4 Medium-chain fatty acid triglyceride in 100 mL 5.0 g Polysorbate 80 4.0 g Condensed glycerin 2.6 g Sodium acetate 0.05 g Benzalkonium chloride 0.005 g Hydrochloric acid Appropriate amount Sterilized purified water Appropriate amount (pH 5.0) Castor oil Was prepared in the same manner as in Comparative Example 1 except that a medium-chain fatty acid triglyceride was used in place of the above.

Test Example 3 Storage Efficacy Test (3) Emulsions of the formulations of Example 6 and Comparative Example 4
A storage efficiency test was performed in the same manner as in Test Example 1. The results are shown in Tables 6 and 7.

[0048]

[Table 6]

[0049]

[Table 7]

From the above results, even when the type of oil is medium-chain fatty acid triglyceride, in the emulsion containing sorbic acid of the formulation of Example 6, bacteria were killed in the first week, and fungal growth was also observed. However, it was shown to have excellent preservative efficacy because it was compatible with the Japanese Pharmacopoeia.

[0051]

EFFECTS OF THE INVENTION The preservative for emulsions of the present invention can impart excellent preservative efficacy to emulsions such as oil-in-water (O / W) emulsions even at low compounding concentrations, and therefore have a high preservability. It is possible to provide an emulsion which is high and has few side effects due to a preservative.
Further, by blending sodium edetate and boric acid, high storage stability can be obtained at a low concentration even in an emulsion having a high pH.

Claims (22)

[Claims] 1. An emulsion preservative containing sorbic acid or a pharmaceutically acceptable salt thereof. 2. The preservative for an emulsion according to claim 1, comprising sorbic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.001 to 5 (W / V)%. 3. The emulsion preservative according to claim 1, which contains sorbic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.01 to 1 (W / V)%. 4. The emulsion preservative according to claim 1, further comprising sodium edetate and boric acid. 5. A sodium edetate containing 0.001 to 0.
2 (W / V)% and boric acid in an amount of 0.001 to 10 (W
5. The preservative according to claim 4, wherein the preservative is contained at a concentration of (/ V)%. 6. A method for preparing sodium edetate from 0.005 to 0.5.
1 (W / V)% and boric acid in an amount of 0.01 to 5 (W / V).
5. The emulsion preservative according to claim 4, which contains V) at a concentration of%. 7. The preservative according to claim 1, wherein the emulsion has a dosage form for eye drops, nasal drops or ear drops. 8. An emulsion containing sorbic acid or a pharmaceutically acceptable salt thereof together with a base drug and a pharmaceutically acceptable carrier. 9. The emulsion according to claim 8, comprising sorbic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.001 to 5 (W / V)%. 10. The emulsion according to claim 8, comprising sorbic acid or a pharmaceutically acceptable salt thereof at a concentration of 0.01 to 1 (W / V)%. 11. The emulsion according to claim 8, further comprising sodium edetate and boric acid. 12. A method for preparing sodium edetate from 0.001 to 0.001.
0.2 (W / V)%, and boric acid in an amount of 0.001 to 10
The emulsion according to claim 11, which is contained at a concentration of (W / V)%. 13. The use of sodium edetate in an amount of from 0.005 to
0.1 (W / V)% and boric acid in an amount of 0.01 to 5 (W
The emulsion according to claim 11, which is contained at a concentration of (/ V)%. 14. The emulsion according to claim 8, which has a dosage form for eye drops, nasal drops, or ear drops. 15. An emulsion containing the preservative for emulsion according to any one of claims 1 to 7 together with a base drug and a pharmaceutically acceptable carrier. 16. A method for preserving an emulsion, comprising incorporating sorbic acid or a pharmaceutically acceptable salt thereof into the emulsion in a concentration effective for preserving the emulsion and at a pharmaceutically acceptable concentration. 17. The method according to claim 16, wherein sorbic acid or a pharmaceutically acceptable salt thereof is incorporated at a concentration of 0.001 to 5 (W / V)%. 18. The method according to claim 16, wherein sorbic acid or a pharmaceutically acceptable salt thereof is incorporated at a concentration of 0.01 to 1 (W / V)%. 19. The method according to any one of claims 16 to 18, wherein sodium edetate and boric acid are further blended in a concentration effective for preserving the emulsion and pharmaceutically acceptable. 20. A sodium edetate containing 0.001 to
0.2 (W / V)%, and boric acid in an amount of 0.001 to 10
20. The method according to claim 19, wherein the composition is blended at a concentration of (W / V)%. 21. A sodium edetate containing 0.005 to
0.1 (W / V)% and boric acid in an amount of 0.01 to 5 (W
The method of claim 19, wherein the compound is formulated at a concentration of (/ V)%. 22. The method according to claim 16, wherein said method is a method for preserving an emulsion having an ophthalmic, nasal or ear dosage form.
22. The method according to any one of to 21.