KR100710639B1 - Transparent liquid preparation containing coenzyme Q10 and preparing method thereof - Google Patents

Abstract

The present invention provides a coenzyme Q10-containing transparent liquid formulation and a method for preparing the same, comprising polyoxyl n castor oil and polyglycerol fatty acid ester. The present invention can provide a transparent and stable coenzyme Q10-containing transparent liquid formulation.

Coenzyme Q10, polyoxyl n castor oil, polyglycerol fatty acid ester

Description

Transparent liquid preparation containing coenzyme # 10 and preparation method thereof

The present invention relates to a liquid formulation containing coenzyme Q10 and a process for preparing the same.

Coenzyme Q10, also called ubidecarenone, is a fat-soluble quinone that is synthesized in cells and participates in the formation of primary cells, and is a coenzyme that plays an important role in mitochondrial electron transport and ATP synthesis. It has been used for the treatment of congestive heart failure, and recently, it has been reported that myocardial protective action, prevention of carcinogenesis, anti-aging, blood LDL oxidation inhibition, blood pressure increase inhibition, etc. due to antioxidant activity has increased.

However, because coenzyme Q10 is poorly soluble in water, alcohol, etc., it is very difficult to use in liquid formulations, and it is difficult to dissolve in the body.

Korean Patent Laid-Open Publication No. 2002-0080370 attempts to overcome the above problem by using cyclodextrin, but this method has a problem that the manufacturing cost increases due to cyclodextrin, and in Japanese Patent Laid-Open Publication No. 2000-212066, coenzyme Q10, Coenzyme Q10 was prepared as an aqueous liquid by mixing an emulsifier, a polyhydric alcohol, and water, and then applying a high pressure. However, such an aqueous liquid solution should not only use an ultra-high pressure of 1000 kg / cm 2, but also have poor stability and may cause coenzyme Q10 to precipitate over time. It is known that Japanese Patent Laid-Open No. P2005-43A is known. In addition, Japanese Patent Application Laid-Open No. P2005-43A attempts to solubilize coenzyme Q10 using hydrophilic polyglycerol ricinoleic acid (caster oil acid) ester, but has the disadvantage of poor transparency and relatively poor storage stability, and coenzyme Q10. If the content of the high is difficult to prepare a transparent liquid formulation.

Therefore, the technical problem to be achieved by the present invention is to provide a coenzyme Q10-containing liquid formulation which is transparent and stable and is present in a dissolved state of coenzyme Q10, thereby improving absorption in vivo.

In order to achieve the above technical problem, the present invention comprises the steps of (A) preparing a mixed solution comprising coenzyme Q10, polyoxyl n castor oil (n is 30 to 40) and polyglycerol fatty acid ester; (B) adding water to the mixture to prepare a water-in-oil (w / o) type emulsion; And (c) adding water to the oil of step (b) to prepare an oil-in-water (o / w) type oil agent. Provides a method for producing a coenzyme Q10-containing transparent liquid formulation comprising a In addition, the present invention also provides a method for producing a coenzyme Q10-containing transparent liquid formulation, characterized in that step (a) and (b) occur simultaneously.

The present invention also provides a method for producing a coenzyme Q10-containing transparent liquid formulation, characterized in that it further comprises ethanol in the mixed solution of step (a).

More preferably, the present invention is coenzyme Q10-containing transparent liquid formulation, characterized in that the polyoxyl n castor oil of step (A) is polyoxyl 35 castor oil, and the polyglycerol fatty acid ester is decaglycerol stearate. It provides a method of manufacturing.

Preferably, the present invention is characterized in that the mixture of step (a) comprises 1.3-20 parts by weight of polyoxyl n castor oil (n is 30 to 40) and 0.28-8 parts by weight of polyglycerol fatty acid ester relative to the weight of coenzyme Q10 Coenzyme Q10 to provide a method for producing a transparent liquid formulation, more preferably, the present invention (A) the mixed solution of polyoxyl n castor oil (n is 30 to 40) 1.5-10 parts by weight and coenzyme Q10 weight and It provides a method for producing a coenzyme Q10 transparent liquid formulation, comprising 0.5-5 parts by weight of a polyglycerol fatty acid ester.

The present invention also provides a coenzyme Q10-containing oil-in-water (o / w) -type transparent emulsion comprising coenzyme Q10, polyoxyl n castor oil (n is 30 to 40), polyglycerol fatty acid ester and water.

More preferably, the present invention is coenzyme Q10-containing oil-in-water, characterized in that it contains 1.3-20 parts by weight of polyoxyl n castor oil (n is 30 to 40) to 0.28-8 parts by weight of polyglycerol fatty acid ester ( o / w) type transparent emulsion.

More preferably, the present invention provides coenzyme Q10-containing oil in water, wherein the polyoxyl n castor oil is polyoxyl 35 castor oil and the polyglycerol fatty acid ester is decaglycerol stearate. o / w) type transparent emulsion.

Hereinafter, the coenzyme Q10-containing transparent liquid formulation of the present invention and a production method thereof will be described in more detail.

The present invention is to prepare a water-in-oil (w / o) emulsion using a coenzyme Q10, polyoxyl n castor oil (n is 30 to 40), polyglycerol fatty acid ester and a small amount of water while gradually adding water step by step The production of oil-in-water (o / w) emulsions using a phase inversion phenomenon can produce a clear liquid formulation containing coenzyme Q10, which is poorly soluble, and is based on the surprising finding that these clear liquid formulations are very stable. . In other words, the present invention is based on the surprising discovery that a phase change phenomenon makes particles of the inner phase containing coenzyme Q10 very fine to produce a transparent and stable emulsion. The oil-in-water emulsion made can be easily prepared into a conventional beverage by adding water since the external phase is water.

The coenzyme Q10-containing oil-in-water transparent emulsion of the present invention includes polyoxyl n castor oil (n is 30 to 40) and polyglycerol fatty acid ester, which serves as an internal oil phase in which coenzyme Q10 can be dissolved and as an emulsifier.

Polyoxyl n castor oil (n is 30-40) is also called polyethylene glycol castor oil and is a nonionic solubilizer prepared by reacting castor oil with ethylene oxide in a molar ratio of 1: 30-40. As the preferred polyoxyl n castor oil (n is 30 to 40), polyoxyl 35 castor oil having n of 35 may be used, but is not limited thereto. Commercially available polyoxyl 35 castor oils are Cremophor ELP ™ or Cremophor EL ™ (BASF, Germany).

Preferred polyglycerol fatty acid esters may include hexa- and tetratradeca-glycerol and esters such as myristic acid, stearic acid, oleic acid, lauric acid, ercaic acid, behenic acid, but are not limited thereto. No, decaglycerol stearate is more preferred.

Coenzyme Q10-containing oil-in-water transparent emulsion of the present invention can be prepared as follows. First, a mixed solution containing coenzyme Q10, polyoxyl n castor oil (n is 30 to 40), a polyglycerol fatty acid ester, and a small amount of water is prepared, and then the mixed solution is stirred, shaken, or homogenized (oil-in-water). (w / o) type emulsions are prepared. In such a water-in-oil emulsion, coenzyme Q10 is present in a dissolved state in the external oil phase. Thereafter, water is added to the water-in-oil emulsion step by step, and the oil-in-water (o / w) emulsion is prepared by causing a phase change by stirring, shaking, or homogenizing. The internal phase of the oil-in-water emulsion in which coenzyme Q10 is dissolved due to the phase change is present as very fine particles to obtain a transparent and stable emulsion.

In the preparation method of the coenzyme Q10-containing oil-in-water transparent emulsion of the present invention, prior to preparing the oil-in-water emulsion, coenzyme Q10, polyoxyl n castor oil (n is 30 to 40) and a polyglycerol fatty acid ester in a mixed solution In order to increase the solubility of coenzyme Q10, ethanol may be added within a range not impairing the object of the present invention.

Coenzyme Q10-containing oil-in-water transparent emulsion of the present invention preferably comprises 1.3-20 parts by weight of polyoxyl n castor oil (n is 30 to 40) and 0.28-8 parts by weight of polyglycerol fatty acid ester relative to the weight of coenzyme Q10, 1.5 More preferably, it comprises -10 parts by weight of polyoxyl n castor oil (n is 30 to 40) and 0.5-5 parts by weight of polyglycerol fatty acid ester. When coenzyme Q10, polyoxyl n castor oil (n is 30 to 40) and polyglycerol fatty acid esters are contained in this ratio, it is easy to prepare a water-in-oil emulsion, produce a phase-in-oil emulsion, and thus are transparent and stable. It is easier to obtain oil-in-water emulsions. Once the oil-in-water emulsion is produced, since the outside is an aqueous phase, the internal fine oil-containing particles containing the oil-in-water type coenzyme Q10 can be stably maintained even if additional water is included for the production of beverages and the like.

The present invention also provides a liquid formulation comprising the coenzyme Q10-containing oil-in-water transparent emulsion of the present invention. The liquid formulation of the present invention may further include a stabilizer, a preservative, a pH adjuster, a flavoring agent, a coloring agent, and the like within the range not impairing the object of the present invention in addition to the emulsion.

It is considered that the liquid formulation of the present invention is not only transparent and stable, which is highly commercial, but also has a good absorption rate of coenzyme Q10 because coenzyme Q10 is dissolved.

Hereinafter, the following examples and the like will be described in order to describe the present invention in more detail. However, embodiments according to the present invention can be modified in many different forms and the scope of the present invention should not be construed as being limited to the embodiments described below. Embodiments of the present invention are provided by way of example in order to facilitate a specific understanding of the present invention.

Comparative Example 1

375 mg of citric acid was added to 400 g of water and stirred at room temperature to completely dissolve. Then, 50 mg of coenzyme Q10 was added thereto, followed by vigorous stirring at 65 ° C. for 20 minutes. After stirring, 187 mg of soybean lecithin was added and stirred at 65 ° C for 30 minutes. Thereafter, 94 mg of xanthan gum was added and stirred at 65 ° C. for 30 minutes to prepare an orange juice-type emulsion containing coenzyme Q10. Precipitation formed over time after preparation and was not stable.

Comparative Example 2

187 mg of citric acid was added to 50 g of water and stirred at room temperature to completely dissolve. Then, 50 mg of coenzyme Q10 was added thereto and stirred vigorously at 65 ° C. for 20 minutes. After stirring, 187 mg of soybean lecithin was added and stirred at 65 ° C for 30 minutes. Then, 50 mg of collagen and 94 mg of xanthan gum were added and stirred at 65 ° C. for 30 minutes to prepare an orange juice-type emulsion containing coenzyme Q10. Precipitation formed over time after preparation and was not stable.

Comparative Example 3

375 mg of citric acid was added to 50 g of water, stirred at room temperature to completely dissolve, and 50 mg of coenzyme Q10 was added thereto, followed by vigorous stirring at 65 ° C. for 20 minutes. After stirring, 1 g of diethylene glycol monoethyl ether (Transcutol ™) was added thereto, stirred for 10 minutes, and then 187 mg of soybean lecithin was added and stirred at 65 ° C. for 30 minutes. Then, 50 mg of collagen and 94 mg of xanthan gum were added and stirred at 65 ° C. for 30 minutes to prepare an orange juice-type emulsion containing coenzyme Q10. Precipitation formed over time after preparation and was not stable.

<Comparative Example 4>

375 mg of citric acid was added to 50 g of water, stirred at room temperature to completely dissolve, and 50 mg of coenzyme Q10 was added thereto, followed by vigorous stirring at 65 ° C. for 20 minutes. After stirring, 1 g of diethylene glycol monoethyl ether (Transcutol ™) and 1 g of glycerol-polyethylene glycol oxystearate (Cremophor RH40 ™) were added and stirred for 20 minutes. Thereafter, 187 mg of soy lecithin was added and stirred at 65 ° C. for 30 minutes, and then 50 mg of collagen and 94 mg of xanthan gum were added and stirred at 65 ° C. for 30 minutes to prepare an orange juice-type emulsion containing coenzyme Q10. Precipitation formed over time after preparation and was not stable.

Comparative Example 5

375 mg of citric acid was added to 50 g of water, and the mixture was stirred at room temperature to completely dissolve. Then, 50 mg of coenzyme Q10 was added thereto and stirred vigorously at 65 ° C. for 20 minutes. After stirring, 187 mg of soybean lecithin was added and stirred at 65 ° C for 30 minutes. Then, 150 mg of chitosan was added and stirred for 20 minutes. Then, xanthan gum 94 mg was added and stirred at 65 ° C. for 30 minutes to prepare a coenzyme Q10-containing emulsion. Precipitation formed during storage after preparation and was not stable.

Comparative Example 6

375 mg of citric acid was added to 50 g of water and stirred at room temperature to completely dissolve. Then, 50 mg of coenzyme Q10 was added thereto and stirred vigorously at 65 ° C. for 30 minutes. After stirring, 2 g of diethylene glycol monoethyl ether (Transcutol ™) and 1 g of glycerol-polyethylene glycol oxystearate (Cremophor RH40 ™) were added and stirred at 65 ° C. for 30 minutes. Thereafter, 187 mg of soybean lecithin was added and stirred for 30 minutes. Then, 150 mg of chitosan was added, stirred at 65 ° C. for 30 minutes, and 94 mg of xanthan gum was added thereto, followed by stirring for 20 minutes, thereby preparing an emulsion containing coenzyme Q10. Precipitation formed during storage after preparation and was not stable.

Comparative Example 7

Ryoto polyglyester SWA-10D ™ (a mixture of 40% decaglycerol stearate, 5% ethanol and 55% water, Mitsubishi-Kagaku Foods Co., Japan) was added to 50 g of water and stirred at 65 ° C for dissolution. Then, 50 mg of coenzyme Q10 was added thereto and stirred vigorously at 65 ° C. for 30 minutes. After adding 500 mg of liquid cyclodextrin, the mixture was stirred for 20 minutes, and 1 g of glycerol-polyethylene glycol oxystearate (Cremophor RH40 ™) was added thereto, followed by stirring for 20 minutes. Then, 187 mg of soy lecithin was added and stirred for 30 minutes to coenzyme Q10. The emulsion contained was prepared. Precipitation formed during storage after preparation and was not stable.

<Comparative Example 8>

500 mg of Ryto polyglyester SWA-10D ™ was added to 50 g of water, stirred at 65 ° C. to dissolve, and then 50 mg of coenzyme Q10 was added and stirred vigorously at 65 ° C. for 30 minutes. Then 500 mg of cyclodextrin was added and stirred again for 20 minutes. Thereafter, 1 g of glycerol-polyethylene glycol oxystearate (Cremophor RH40 ™) was added and stirred for 20 minutes. Then, 187 mg of soy lecithin was added and stirred for 30 minutes to prepare an emulsion containing coenzyme Q10. Precipitation formed during storage after preparation and was not stable.

Comparative Example 9

Add 50 g of coenzyme Q10, 1 g of glycerol-polyethylene glycol oxystearate (Cremophor RH40 ™) and 1 g of polyoxyl 35 castor oil (Cremophor ELP ™), dissolve at 65 ° C, add 500 mg of liquid cyclodextrin, and 30 minutes with 50 g of water. Stirred. After stirring, 2 g of diethylene glycol monoethyl ether (Transcutol ™) was added thereto, stirred for 20 minutes, and 150 mg of chitosan was added thereto, followed by stirring at 65 ° C. for 30 minutes to prepare a coenzyme Q10-containing liquid formulation. As a result, coenzyme Q10 was not dissolved.

Comparative Example 10

50 mg of coenzyme Q10 and 500 mg of liquid cyclodextrin were added and dissolved at 65 ° C. Then, 2 g of diethylene glycol monoethyl ether (Transcutol ™) was added and stirred with 500 g of water for 30 minutes. After stirring, 375 mg of chitosan was added thereto, followed by stirring at 65 ° C. for 30 minutes to prepare a coenzyme Q10-containing liquid formulation. As a result, coenzyme Q10 was not dissolved.

Comparative Example 11

Add 50 mg of coenzyme Q10, 500 mg of liquid cyclodextrin, and 1 g of polyoxyl 35 castor oil (Cremophor ELP ™) and dissolve at 65 ° C. Then, add 2 g of diethylene glycol monoethyl ether (Transcutol ™) and add 50 g of water for 30 minutes at 65 ° C. Was stirred to prepare a coenzyme Q10 containing liquid formulation. As a result, coenzyme Q10 was not dissolved.

Comparative Example 12

50 mg of coenzyme Q10, 500 mg of liquid cyclodextrin, and 1 g of polyoxyl 35 castor oil (Cremophor ELP ™) were dissolved at 65 ° C. Then, 2 g of diethylene glycol monoethyl ether (Transcutol ™) was added and stirred with 500 g of water for 30 minutes. . After stirring, 375 mg of chitosan was added thereto, followed by stirring at 65 ° C. for 30 minutes to prepare a coenzyme Q10-containing liquid formulation. As a result, coenzyme Q10 was not dissolved.

Comparative Example 13

50 mg of coenzyme Q10, 200 mg of sucrose fatty acid ester (sucrose stearic acid ester), and 94 mg of decaglycerol stearate were added and dissolved at 65 ° C., followed by stirring at 50 ° C. with 50 g of water for 30 minutes to prepare a coenzyme Q10-containing liquid formulation. As a result, coenzyme Q10 was not dissolved.

<Examples 1-10>

To prepare a coenzyme Q10-containing liquid formulation in the composition and content of Table 1. Ryoto polyglyester ester SWA-10D ™ (a mixture of 40% decaglycerol stearate, 5% ethanol and 55% water, Mitsubishi-Kagaku Foods Co., Japan), polyoxyl 35 castor oil (cremophor ELP ™, BASF Co., Germany) and coenzyme Q10 were mixed and then dissolved by warming and stirring at about 65 ° C. for 5 minutes. Thereafter, 1000 ml of water was gradually added thereto, followed by stirring to obtain a composition containing coenzyme Q10.

(Unit: g) SWA-10D ™ Cremophor ELP ™ Coenzyme Q10 Manufacture results Example 1 0.35 1.25 One muddiness Example 2 0.7 1.25 One muddiness Example 3 1.25 1.25 One Slightly turbid Example 4 1.5 1.25 One Slightly turbid Example 5 1.48 2.5 One Transparency Example 6 1.5 2 One Transparency Example 7 1.5 1.75 One Transparency Example 8 1.5 2 One Transparency Example 9 20 20 One Transparency Example 10 0.7 1.3 One Transparency

As shown in the results of Table 1 above, a transparent coenzyme Q10-containing liquid formulation was obtained when a polyoxyl n castor oil (n is 30 to 40) and a polyglycerol fatty acid ester having a predetermined content or more.

Experimental Example 1 Evaluation of Stability

As a result of evaluating the property stability of the coenzyme Q10-containing transparent liquid formulations of Examples 5 to 10, it was stable without changing the properties for 60 days at room temperature, 40 ° C, 50 ° C, 60 ° C, and thawing conditions after freezing.

In addition, the content stability of the coenzyme Q10-containing transparent liquid formulation prepared in Example 8 was evaluated, and the results of the residual content (percent) compared to the content before the start of the stability evaluation experiment are shown in Table 2.

1 week 2 weeks 4 Weeks 6 Weeks 12 Weeks content (%) Room temperature 95 96 96 94 94 40 ℃ 96 93 93 95 5 50 ℃ 93 94 92 91 95 60 ℃ 93 95 93 92 93 Thaw after freezing 95 94 94 95 94 Constellation Transparency Transparency Transparency Transparency Transparency

As can be seen from the results of Table 2, the coenzyme Q10-containing transparent liquid formulation of the present invention can be seen that the coenzyme Q10 is protected from the external environment and stable.

The present invention provides a transparent and stable coenzyme Q10-containing liquid formulation and a method for preparing the same. In addition, since the coenzyme Q10-containing liquid formulation of the present invention is present in a dissolved state of coenzyme Q10, absorption in vivo may be improved.

Claims (10)

(A) coenzyme Q10; Polyoxyl n castor oil (n is 30 to 40); And a polyglycerol fatty acid ester which is an ester of hexa- to tetratradeca-glycerol and any one selected from the group consisting of myristic acid, stearic acid, oleic acid, lauric acid, ercaic acid and behenic acid. Preparing a mixed liquid; (B) adding water to the mixture to prepare a water-in-oil (w / o) type emulsion; And (C) adding water to the oil of step (b) to prepare an oil-in-water (o / w) emulsion; Method for producing a coenzyme Q10-containing transparent liquid formulation comprising a. The method of claim 1, wherein the steps (a) and (b) occur simultaneously. The method according to claim 1, wherein the mixed solution of step (a) further comprises ethanol. The method of claim 1, wherein the polyoxyl n castor oil of step (a) is a polyoxyl 35 castor oil. The method according to claim 1, wherein the polyglycerol fatty acid ester of step (a) is decaglycerol stearate (decaglycerol stearate). According to claim 1, wherein the mixed solution of step (a) is characterized in that it comprises 1.3-20 parts by weight of polyoxyl n castor oil (n is 30 to 40) and 0.28-8 parts by weight of polyglycerol fatty acid ester to the weight of coenzyme Q10 A method for producing a coenzyme Q10 transparent liquid formulation. The mixed solution of step (a) is characterized in that it comprises 1.5-10 parts by weight of polyoxyl n castor oil (n is 30 to 40) and 0.5-5 parts by weight of polyglycerol fatty acid ester based on the weight of coenzyme Q10. A method for producing a coenzyme Q10 transparent liquid formulation. Coenzyme Q10; Polyoxyl n castor oil (n is 30 to 40); Polyglycerol fatty acid esters which are esters of hexa- to tetratradeca-glycerol with any one selected from the group consisting of myristic acid, stearic acid, oleic acid, lauric acid, ercaic acid and behenic acid; And coenzyme Q10-containing oil-in-water (o / w) type transparent emulsion, comprising water. The coenzyme Q10-containing water according to claim 8, wherein the emulsion contains 1.3-20 parts by weight of polyoxyl n castor oil (n is 30 to 40) and 0.28-8 parts by weight of polyglycerol fatty acid ester relative to the weight of coenzyme Q10. Heavy oil (o / w) clear emulsion. The coenzyme Q10-containing oil-in-water (o / w) -type transparent emulsion according to claim 8, wherein the polyoxyl n castor oil is polyoxyl 35 castor oil and the polyglycerol fatty acid ester is decaglycerol stearate. .