A chlorogenic acid self-emulsifying composition capsule and preparation method thereof

Abstract

The present invention provides a chlorogenic acid self-emulsifying composition capsule and a preparation method thereof. The chlorogenic acid self-emulsifying composition capsule of the present invention comprises a capsule shell and a chlorogenic acid self-emulsifying composition wrapped in the capsule shell; the chlorogenic acid self-emulsifying composition comprises a complex formed by chlorogenic acid and a lipid material, an oil phase, an emulsifier and an emulsifier; the capsule shell is a hard capsule or a soft capsule, and the soft capsule does not contain gelatin. The chlorogenic acid self-emulsifying composition capsule provided by the present invention has good stability, and the drug does not migrate in gelatin hard capsules, hydroxypropyl methylcellulose hard capsules and starch hard capsules.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and in particular relates to a chlorogenic acid self-emulsifying composition capsule and a preparation method thereof. Background Art

[0002] Chlorogenic acid is a phenolic acid composed of caffeic acid and quinic acid, also known as coffee tannin. It is a phenylpropanoid compound produced by plants through the shikimic acid pathway during aerobic respiration. Chlorogenic acid is widely found in plants such as honeysuckle, eucommia leaves, sunflower seeds, artemisia capillaris and blue pot flower, and has multiple pharmacological effects such as antioxidant, antibacterial, antiviral, hypoglycemic, lipid-lowering, hypotensive and immunomodulatory.

[0003] CN110179750A discloses a chlorogenic acid self-emulsifying composition and its use, wherein the chlorogenic acid self-emulsifying composition is a uniform oily liquid formed by an oil phase, an emulsifier and an emulsifier. However, the prior art does not disclose a capsule filling or preparation method suitable for the chlorogenic acid self-emulsifying composition.

[0004] In order to facilitate oral administration and quantitative measurement of liquid medicines, they are generally placed in capsules made of gelatin, glycerin or other suitable pharmaceutical materials alone or in combination. The preparation methods include dripping, compression and filling.

[0005] The dripping method is completed by a dripping pill machine with a double-layer dripper. Specifically, the gelatin solution and the oily drug solution are respectively placed in a liquid storage tank, and the two liquids are sprayed at different speeds through a concentric tubular double-layer nozzle, so that a certain amount of gelatin liquid wraps a certain amount of drug solution, and then drips into another immiscible coolant. After the gelatin liquid contacts the coolant, it becomes spherical due to surface tension and gradually solidifies into a soft capsule.

[0006] The pressing method is to make the gelatin into a film of uniform thickness, then place the drug solution between two films, and use a steel plate mold or a rotary mold to press the soft capsule. At present, the rotary molding method is mainly used in production (the shape of the mold can be elliptical, spherical or other shapes). The filling method is to directly fill the drug solution into the formed hard capsule made of gelatin or other capsule materials.

[0007] CN1449766A discloses a Yinhuang soft capsule preparation and a preparation method thereof, which contains honeysuckle extract, baicalin, honeysuckle volatile oil, solvent and stabilizer, wherein the honeysuckle extract contains chlorogenic acid. The Chinese invention patent application with publication number CN1939408B discloses a Yinhuang liquid capsule and a preparation method thereof. The background technology of the patent application mentions that the Yinhuang gelatin soft capsule disclosed in the Chinese invention patent application with publication number CN1449766A will disintegrate and migrate its contents after being stored for a period of time due to the volatilization of its active ingredient volatile oil. CN1939408B determines the optimal ratio between raw materials and auxiliary materials through exploratory experiments to ensure the stable quality of the Yinhuang liquid capsule. As each drug disclosed in CN1939408B has its specific physical and chemical properties, a general technical solution cannot be directly applied to the preparation of a specific drug preparation with specific physical and chemical properties without creative experimental research. The liquid capsule preparation method in the patent may not be suitable for other drug preparations. Therefore, developing a method for preparing liquid capsules suitable for chlorogenic acid self-emulsifying compositions has important application value. Summary of the invention

[0008] The object of the present invention is to provide a chlorogenic acid self-emulsifying composition capsule with good stability, wherein the chlorogenic acid self-emulsifying composition capsule has a small migration amount in a soft capsule shell not containing gelatin, and the chlorogenic acid migration rate in hydroxypropyl methylcellulose and starch soft capsules is less than 3%; and almost no migration occurs in gelatin hard capsules, hydroxypropyl methylcellulose hard capsules and starch hard capsules.

[0009] The present invention unexpectedly found that a large amount of chlorogenic acid will migrate in the gelatin soft capsule of the chlorogenic acid self-emulsifying composition during the preparation process, and as the storage time increases, the drug further migrates, resulting in damage to the drug content. The present invention provides a method for reducing the migration of chlorogenic acid in the chlorogenic acid self-emulsifying composition to the capsule shell during the preparation and storage process, and a chlorogenic acid self-emulsifying composition hard capsule and a chlorogenic acid self-emulsifying composition soft capsule with good stability.

[0010] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0011] In a first aspect, the present invention provides a chlorogenic acid self-emulsifying composition capsule, wherein the chlorogenic acid self-emulsifying composition capsule comprises a capsule shell and a chlorogenic acid self-emulsifying composition wrapped in the capsule shell;

[0012] The chlorogenic acid self-emulsifying composition comprises a complex formed by chlorogenic acid and a lipid material, an oil phase, an emulsifier and an emulsifier aid; the capsule shell is a hard capsule or a soft capsule, and the soft capsule does not contain gelatin.

[0013] In the present invention, the chlorogenic acid self-emulsifying composition has a small migration amount in the soft capsule shell without gelatin and can be stably stored.

[0014] In the present invention, the chlorogenic acid mobility = 1 - (the content of chlorogenic acid in the contents after capsule molding / the content of chlorogenic acid in the contents before capsule molding).

[0015] Preferably, the raw materials for preparing the soft capsule include a rubber material, a plasticizer, water and an optional preservative.

[0016] Preferably, the raw materials for preparing the soft capsule include, by weight: 35-45 parts of a rubber material, 5-7 parts of a plasticizer, 140-180 parts of water, and 0-0.6 parts of a preservative.

[0017] In the present invention, the weight proportion of the rubber material in the raw materials for preparing the soft capsule is 35 to 45 parts, for example, 35 parts, 38 parts, 40 parts, 42 parts or 45 parts.

[0018] In the present invention, the weight proportion of the plasticizer in the raw materials for preparing the soft capsule is 5 to 7 parts, for example, 5 parts, 5.5 parts, 6 parts, 6.5 parts or 7 parts.

[0019] In the present invention, the weight proportion of water in the raw materials for preparing the soft capsule is 140 to 180 parts, for example, 140 parts, 150 parts, 160 parts, 170 parts or 180 parts.

[0020] In the present invention, the weight proportion of the preservative in the raw materials for preparing the soft capsule is 0 to 0.6 parts, for example, it can be 0.1 parts, 0.2 parts, 0.3 parts, 0.4 parts, 0.5 parts or 0.6 parts.

[0021] In the present invention, the content of each component of the raw material of the soft capsule affects the stability of the final capsule preparation. When the amount of the sizing agent is increased and the amount of water is reduced, the resulting capsule shell has weak elasticity and high hardness, and is difficult to form during preparation. When the amount of the sizing agent is reduced and the amount of the plasticizer is increased, the resulting capsule shell becomes soft, has an uneven thickness, and has a large amount of chlorogenic acid migration.

[0022] Preferably, the rubber material comprises semi-synthetic polymer material and / or natural polymer material.

[0023] Preferably, the semi-synthetic polymer material comprises a cellulose-based polymer material.

[0024] Preferably, the cellulose-based polymer material includes any one of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, cellulose acetate phthalate, methyl cellulose or ethyl cellulose, or a combination of at least two thereof.

[0025] Preferably, the natural polymer material includes starch-based polymer material.

[0026] Preferably, the starch-based polymer material includes natural starch and / or modified starch.

[0027] Preferably, the natural starch comprises corn starch and / or tapioca starch.

[0028] Preferably, the modified starch includes any one of grafted starch, oxidized starch or pregelatinized starch, or a combination of at least two thereof.

[0029] Preferably, the grafted starch comprises hydroxypropyl carboxymethyl starch and / or carboxymethyl starch.

[0030] In the present invention, the chlorogenic acid mobility of the chlorogenic acid self-emulsifying composition in the hydroxypropyl methylcellulose and starch soft capsule is less than 3%.

[0031] Preferably, the plasticizer includes any one of sorbitol, mannitol or glycerol, or a combination of at least two of them.

[0032] Preferably, the preservative includes any one of methylparaben, butylparaben or ethylparaben, or a combination of at least two of them.

[0033] Preferably, the raw materials for preparing the hard capsule include: a sizing agent, a plasticizer, a gelling agent, water and an optional preservative.

[0034] Preferably, the raw materials for preparing the hard capsule include, by weight: 100-200 parts of a rubber material, 10-14 parts of a plasticizer, 12-15 parts of a gelling agent, 200-600 parts of water, and 0-0.6 parts of a preservative.

[0035] In the present invention, the weight proportion of the rubber material in the raw materials for preparing the hard capsule is 100 to 200 parts, for example, 100 parts, 120 parts, 140 parts, 150 parts, 160 parts, 180 parts or 200 parts.

[0036] In the present invention, the weight proportion of the plasticizer in the raw materials for preparing the hard capsule is 10 to 14 parts, for example, 10 parts, 11 parts, 12 parts, 13 parts or 14 parts.

[0037] In the present invention, the weight proportion of the gelling agent in the raw materials for preparing the hard capsule is 12 to 15 parts, for example, 12 parts, 13 parts, 14 parts or 15 parts.

[0038] In the present invention, the weight proportion of water in the raw materials for preparing the hard capsule is 200 to 600 parts, for example, 200 parts, 250 parts, 300 parts, 350 parts, 400 parts, 450 parts, 500 parts, 550 parts or 600 parts.

[0039] In the present invention, the weight proportion of the preservative in the raw materials for preparing the hard capsule is 0 to 0.6 parts, for example, it can be 0.1 parts, 0.2 parts, 0.3 parts, 0.4 parts, 0.5 parts or 0.6 parts.

[0040] Preferably, the rubber material of the hard capsule includes semi-synthetic polymer material and / or natural polymer material.

[0041] Preferably, the semi-synthetic polymer material comprises a cellulose-based polymer material.

[0042] Preferably, the cellulose-based polymer material is any one of hydroxypropylmethylcellulose, sodium carboxymethylcellulose, cellulose acetate phthalate, methylcellulose or ethylcellulose, or a combination of at least two thereof, preferably hydroxypropylmethylcellulose.

[0043] Preferably, the natural polymer material includes starch polymer material and / or gelatin.

[0044] Preferably, the starch-based polymer material includes natural starch and / or modified starch.

[0045] Preferably, the natural starch comprises corn starch and / or tapioca starch.

[0046] Preferably, the modified starch includes any one of grafted starch, oxidized starch or pregelatinized starch, or a combination of at least two thereof.

[0047] Preferably, the grafted starch comprises hydroxypropyl carboxymethyl starch and / or carboxymethyl starch.

[0048] In the present invention, the chlorogenic acid self-emulsifying composition hardly migrates in gelatin hard capsules, hydroxypropyl methylcellulose hard capsules and starch hard capsules, indicating that the chlorogenic acid self-emulsifying composition is best stored in hard capsules.

[0049] Preferably, the plasticizer includes any one of sorbitol, mannitol or glycerol, or a combination of at least two of them.

[0050] Preferably, the gelling agent comprises any one of gum arabic, carrageenan or pectin, or a combination of at least two of them.

[0051] Preferably, the preservative includes any one of methylparaben, butylparaben or ethylparaben, or a combination of at least two of them.

[0052] Preferably, the capsule shell is a hard capsule, and the specifications of the capsule shell are:

[0053] The length of the cap is 10.8 to 11.20 mm, for example, it can be 10.8 mm, 11.0 mm or 11.2 mm;

[0054] The body length is 18.40 to 18.80 mm, for example, 18.40 mm, 18.60 mm or 18.80 mm;

[0055] The wall thickness is 0.085-0.115 mm, for example, 0.085 mm, 0.095 mm, 0.105 mm, 0.115 mm, etc.

[0056] The body wall thickness is 0.085 to 0.115 mm, for example, it can be 0.085 mm, 0.095 mm, 0.105 mm, 0.115 mm, etc.

[0057] Preferably, the content of chlorogenic acid in the chlorogenic acid self-emulsifying composition is 5 to 200 mg / g, preferably 10 to 150 mg / g.

[0058] The content of chlorogenic acid in the chlorogenic acid self-emulsifying composition of the present invention is 5 to 200 mg / g, for example, 5 mg / g, 10 mg / g, 20 mg / g, 40 mg / g, 60 mg / g, 80 mg / g, 100 mg / g, 120 mg / g, 140 mg / g, 150 mg / g, 160 mg / g, 180 mg / g or 200 mg / g, etc.

[0059] In a second aspect, the present invention provides a method for preparing the chlorogenic acid self-emulsifying composition capsule according to the first aspect, the method for preparing the chlorogenic acid self-emulsifying composition capsule comprising: encapsulating the chlorogenic acid self-emulsifying composition into a capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.

[0060] Preferably, the capsule shell is a hard capsule shell, and the preparation method comprises the following steps:

[0061] The chlorogenic acid self-emulsifying composition is filled into a hard capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.

[0062] Preferably, the temperature of the filled contents is 20-25°C, for example, 20°C, 21°C, 22°C, 23°C, 24°C or 25°C.

[0063] Preferably, the capsule shell is a soft capsule shell, and the preparation method comprises the following steps:

[0064] The capsule material of the soft capsule is liquefied, and the chlorogenic acid self-emulsifying composition is encapsulated in the soft capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.

[0065] Preferably, the step of liquefying the capsule material comprises:

[0066] Heat the water, add the optional preservative according to the formula amount and stir until dissolved, then add the rubber and plasticizer, and degas after dissolving.

[0067] Preferably, the heating temperature is 50-60°C, for example, 30°C, 35°C, 40°C, 45°C or 50°C.

[0068] Preferably, the degassing is carried out by a vacuum pump, and the degassing pressure is 0.05-0.1 MPa, for example, it can be 0.05 MPa, 0.06 MPa, 0.07 MPa, 0.08 MPa, 0.09 MPa or 0.1 MPa, etc., and the degassing time is 20-30 min, for example, it can be 20 min, 21 min, 23 min, 25 min, 27 min, 29 min or 30 min, etc.

[0069] Preferably, the encapsulation method comprises a pressing method or a dripping method.

[0070] Preferably, the pressing process comprises the following steps:

[0071] The liquefied rubber liquid is made into a sheet, coated on a rubber wheel, cooled to form a rubber skin, the chlorogenic acid self-emulsifying composition is sprayed out from a nozzle, and a roller mold is used to cut the rubber skin to form a soft capsule.

[0072] Preferably, the filling amount of the chlorogenic acid self-emulsifying composition is 0.1 to 0.6 mL / grain, for example, 0.1 mL / grain, 0.2 mL / grain, 0.3 mL / grain, 0.4 mL / grain, 0.5 mL / grain or 0.6 mL / grain.

[0073] Preferably, the cooling temperature is 10-20°C, for example, it can be 10°C, 15°C, 16°C, 17°C, 18°C, 19°C or 20°C.

[0074] In the present invention, when preparing soft capsules by compression, the glue liquid is made into a film with uniform thickness, and then the drug solution is placed between two films, and the soft capsules are compressed by a steel plate mold or a rotary mold. The shape of the mold by the rotary molding method can be elliptical, spherical or other shapes.

[0075] Preferably, the step of the dripping method comprises the following steps:

[0076] The liquefied gel and chlorogenic acid self-emulsifying composition are dripped out from a nozzle and cooled in an oily coolant to form a spherical soft capsule.

[0077] Preferably, the filling amount of the contents of the chlorogenic acid self-emulsifying composition capsule is 0.1 to 0.6 mL / capsule, for example, 0.1 mL / capsule, 0.2 mL / capsule, 0.3 mL / capsule, 0.4 mL / capsule, 0.5 mL / capsule or 0.6 mL / capsule, etc.;

[0078] Preferably, the oily coolant includes any one of vegetable oil, silicone oil or liquid paraffin, or a combination of at least two of them.

[0079] Preferably, the cooling temperature is 10-20°C, for example, it can be 10°C, 15°C, 16°C, 17°C, 18°C, 19°C or 20°C.

[0080] In the present invention, the soft capsule is prepared by the dripping method using a pill dropping machine with a double-layer dripper. Specifically, gelatin solution and oily drug solution are respectively contained in a liquid storage tank, and the two liquids are sprayed at different speeds through a concentric tubular double-layer nozzle, so that a certain amount of gelatin solution wraps a certain amount of drug solution, and then drips into another mutually immiscible cooling liquid. After the gelatin solution contacts the cooling liquid, it becomes spherical due to the surface tension, and gradually solidifies to form a soft capsule.

[0081] Compared with the prior art, the present invention has the following beneficial effects:

[0082] (1) The present invention provides a method for reducing the migration of chlorogenic acid in a chlorogenic acid self-emulsifying composition into a capsule shell during preparation and storage, and a chlorogenic acid self-emulsifying composition hard capsule and a chlorogenic acid self-emulsifying composition soft capsule with good stability.

[0083] (2) The chlorogenic acid self-emulsifying composition capsule provided by the present invention has a small migration amount in the soft capsule shell without gelatin, and the chlorogenic acid migration rate in hydroxypropyl methylcellulose and starch soft capsules is less than 3%; almost no migration occurs in gelatin hard capsules, hydroxypropyl methylcellulose hard capsules and starch hard capsules. The chlorogenic acid self-emulsifying composition capsule provided by the present invention has good stability and low chlorogenic acid migration rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0084] Figure 1 This is a picture of the finished product of the chlorogenic acid self-emulsifying composition hard capsule in Example 1.

[0085] Figure 2 This is a finished product picture of the chlorogenic acid self-emulsifying composition gelatin soft capsule in Comparative Example 1. DETAILED DESCRIPTION

[0086] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0087] The preparation method of the chlorogenic acid self-emulsifying composition described in the embodiment:

[0088] (1) Preparation of chlorogenic acid lipid complex

[0089] Soybean lecithin was used as the lipid material, chlorogenic acid and soybean lecithin were added in a mass ratio of 1:2.2, and added together into a 1L round-bottom flask, and anhydrous ethanol was used as the solvent to control the drug concentration at 60 mg / mL. After the chlorogenic acid and soybean lecithin were completely dissolved, they were placed at room temperature for 15 minutes, and then the anhydrous ethanol was removed by rotary evaporation at 100 rpm and 40°C. After the ethanol was evaporated to dryness, the ethanol was removed by continued vacuum drying at 100 rpm at room temperature for 1 hour. The chlorogenic acid lipid complexes obtained were all fully compounded, and the compounding rate was above 99%.

[0090] (2) Preparation of blank self-emulsifying concentrate

[0091] Ethyl oleate, an emulsifier (labrasol as an emulsifier) ​​and a co-emulsifier (transcutol HP as a co-emulsifier) ​​were weighed in a mass ratio of 2:5:3, and the mixture was stirred and mixed to obtain the blank self-emulsifying concentrate.

[0092] (3) Preparation of chlorogenic acid self-emulsifying composition

[0093] Based on a drug loading of 60 mg (in terms of chlorogenic acid), the chlorogenic acid lipid complex obtained in step (1) and the blank self-emulsifying concentrate obtained in step (2) were mixed and placed in an air bath oscillator at a temperature of 25° C. and a rotation speed of 210 rpm to obtain the chlorogenic acid self-emulsifying composition.

[0094] Example 1

[0095] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the raw materials for preparing the hard capsule shell include, by weight: 100 parts of hydroxypropyl methylcellulose, 10 parts of sorbitol, 12 parts of gum arabic, 300 parts of water and 0.4 parts of methyl parahydroxybenzoate.

[0096] The capsule shell is a hard capsule, and the specifications of the capsule shell are:

[0097] The length of the cap is 11.20mm, the length of the body is 18.80mm, the wall thickness of the cap is 0.115mm, and the wall thickness of the body is 0.115mm.

[0098] The chlorogenic acid self-emulsifying composition was filled into a hard capsule shell. The temperature of the filled contents was 25° C. The filling amount of the chlorogenic acid self-emulsifying composition was 0.5 mL / capsule to obtain the chlorogenic acid self-emulsifying composition capsule. The finished product of the obtained chlorogenic acid self-emulsifying composition hard capsule is shown in FIG. Figure 1 shown.

[0099] Example 2

[0100] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the raw materials for preparing the hard capsule shell include, by weight: 120 parts of sodium carboxymethyl cellulose, 12 parts of sorbitol, 13 parts of gum arabic, 300 parts of water and 0.5 parts of methyl parahydroxybenzoate.

[0101] The preparation method is as in Example 1.

[0102] Example 3

[0103] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the raw materials for preparing the hard capsule shell include, by weight: 120 parts of pregelatinized starch, 14 parts of sorbitol, 15 parts of gum arabic, 300 parts of water and 0.4 parts of methyl parahydroxybenzoate.

[0104] The preparation method is as in Example 1.

[0105] Example 4

[0106] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the raw materials for preparing the hard capsule shell include, by weight: 100 parts of gelatin, 10 parts of sorbitol, 12 parts of gum arabic, 300 parts of water and 0.4 parts of methyl parahydroxybenzoate.

[0107] The preparation method is as in Example 1.

[0108] Example 5

[0109] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the raw materials for preparing the soft capsule shell include, by weight: 40 parts of hydroxypropyl methylcellulose, 6 parts of glycerol, 150 parts of water and 0.2 parts of methyl parahydroxybenzoate.

[0110] The preparation method steps are as follows:

[0111] Heat water to 50°C, add methyl paraben and stir until dissolved, then add hydroxypropyl methylcellulose and sorbitol, and use a vacuum pump to degas after dissolution. The degassing pressure is 0.1 MPa and the degassing time is 20 minutes.

[0112] The liquefied rubber liquid is made into a sheet, coated on a rubber wheel, cooled at 10°C to form a rubber skin, and the chlorogenic acid self-emulsifying composition is sprayed out from a nozzle. The filling amount of the chlorogenic acid self-emulsifying composition is 0.5 mL / grain, and the rubber skin is cut by a roller mold to form a soft capsule.

[0113] Example 6

[0114] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the raw materials for preparing the soft capsule shell include, by weight: 35 parts of hydroxypropyl methylcellulose, 6.5 parts of glycerol, 140 parts of water and 0.2 parts of methyl parahydroxybenzoate.

[0115] The preparation method steps are as follows:

[0116] Heat water to 60°C, add methyl paraben and stir until dissolved, then add hydroxypropyl methylcellulose and sorbitol, and use a vacuum pump to degas after dissolution. The degassing pressure is 0.05 MPa and the degassing time is 30 minutes.

[0117] The liquefied gel and the chlorogenic acid self-emulsifying composition were dripped out from the nozzle and cooled in vegetable oil at a temperature of 20° C. to obtain spherical soft capsules. The filling amount of the chlorogenic acid self-emulsifying composition capsules was 0.5 mL / capsule.

[0118] Example 7

[0119] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the raw materials for preparing the soft capsule shell include, by weight: 45 parts of pregelatinized starch, 7 parts of glycerol, 180 parts of water and 0.2 parts of methyl parahydroxybenzoate.

[0120] The preparation method is similar to that of Example 5.

[0121] Example 8

[0122] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the raw materials for preparing the soft capsule shell include, by weight: 40 parts of sodium carboxymethyl cellulose, 6 parts of glycerol, 150 parts of water and 0.2 parts of methyl parahydroxybenzoate.

[0123] The preparation method is similar to that of Example 5.

[0124] Example 9

[0125] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the raw materials for preparing the soft capsule shell include, by weight: 25 parts of hydroxypropyl methylcellulose, 5 parts of glycerol, 140 parts of water and 0.2 parts of methyl parahydroxybenzoate.

[0126] The preparation method is similar to that of Example 5.

[0127] Comparative Example 1

[0128] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the raw materials for preparing the soft capsule shell include, by weight: 40 parts of gelatin, 6 parts of glycerol, 150 parts of water and 0.2 parts of methyl parahydroxybenzoate.

[0129] The preparation method is as shown in Example 5. The finished product of the chlorogenic acid self-emulsifying composition gelatin soft capsule is as shown in FIG. Figure 2 shown.

[0130] Comparative Example 2

[0131] The present embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein the capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the raw materials for preparing the soft capsule shell include, by weight: 40 parts of gelatin, 6 parts of glycerol, 200 parts of water and 0.2 parts of methyl parahydroxybenzoate.

[0132] The preparation method is similar to that of Example 5.

[0133] Test Example 1

[0134] The chlorogenic acid content in the chlorogenic acid self-emulsifying composition capsules described in Examples 1 to 9 and Comparative Examples 1 to 2 was measured under accelerated conditions (25°C, 60% humidity) for 6 months and long-term conditions (4°C refrigerator) for 12 months. The test results are shown in Table 1:

[0135] Determination method:

[0136] The content of chlorogenic acid in the prepared capsules was determined by HPLC. The content of chlorogenic acid after molding determined by HPLC / the dosage of chlorogenic acid.

[0137] Table 1

[0138]

[0139] The chlorogenic acid self-emulsifying composition has no chlorogenic acid migration in the capsule shells of Examples 1 to 4 during the preparation process, accelerated conditions, and long-term conditions. The mobility results of chlorogenic acid in Examples 1 to 4 show that the chlorogenic acid self-emulsifying composition does not migrate in hydroxypropyl methylcellulose hard capsules, sodium carboxymethyl cellulose hard capsules, pregelatinized starch hard capsules, and gelatin hard capsules, indicating that the chlorogenic acid self-emulsifying composition has the best effect when stored in hard capsules.

[0140] It can be seen from the mobility results of chlorogenic acid in Examples 5 to 8 that the chlorogenic acid self-emulsifying composition has a mobility of 1% during the preparation of hydroxypropyl methylcellulose soft capsules, a mobility of 2% under accelerated conditions, and a mobility of 1% under long-term conditions; in the preparation of pregelatinized starch soft capsules, the mobility is 2%, the mobility under accelerated conditions is 3%, and the mobility under long-term conditions is 2%; in the preparation of sodium carboxymethyl cellulose soft capsules under accelerated conditions, the mobility is 2%, the mobility is 3%, and the mobility under long-term conditions is 2%; the results show that the chlorogenic acid self-emulsifying composition can be preserved for a long time in hydroxypropyl methylcellulose soft capsules, pregelatinized starch soft capsules and sodium carboxymethyl cellulose soft capsules.

[0141] It can be seen from the migration results of chlorogenic acid in Example 5 and Example 9 that when the amount of the sizing agent is reduced, the relative contents of glycerol and water in the capsule shell increase, the capsule shell becomes soft, the thickness is uneven, and the migration amount of chlorogenic acid is large.

[0142] By comparing the mobility results of chlorogenic acid in Example 5 with those in Comparative Examples 1 to 2, it can be seen that the mobility of the chlorogenic acid self-emulsifying composition under the accelerated conditions of the soft capsule shell containing gelatin is 16%; the results show that the chlorogenic acid self-emulsifying composition is not suitable for using a soft capsule shell containing gelatin, and the soft capsule shell containing gelatin will adsorb the active ingredients in the chlorogenic acid self-emulsifying composition, affecting the stability of the chlorogenic acid self-emulsifying composition.

[0143] In summary, the present invention found that the migration amount of the chlorogenic acid self-emulsifying composition in the soft capsule shell without gelatin was small, and the chlorogenic acid migration rate in hydroxypropyl methylcellulose and starch soft capsules was less than 3%; almost no migration occurred in gelatin hard capsules, hydroxypropyl methylcellulose hard capsules and starch hard capsules, indicating that the chlorogenic acid self-emulsifying composition is best stored in hard capsules, followed by starch soft capsules and hydroxypropyl methylcellulose soft capsules, and gelatin soft capsules have the worst effect.

[0144] The chlorogenic acid self-emulsifying composition capsule provided by the present invention has a capsule shell that can protect the main component from the effects of oxygen and water molecules in the air, can be stored for a long time, and has improved drug stability. At the same time, the content is liquid for easy absorption.

[0145] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. A chlorogenic acid self-emulsifying composition capsule, It is characterized in that The chlorogenic acid self-emulsifying composition capsule comprises a capsule shell and a chlorogenic acid self-emulsifying composition wrapped in the capsule shell; The chlorogenic acid self-emulsifying composition comprises a complex formed by chlorogenic acid and a lipid material, an oil phase, an emulsifier and an emulsifier aid; The capsule shell is a soft capsule, and the soft capsule does not contain gelatin; The raw materials for preparing the soft capsule shell include, by weight: 35-45 parts of a rubber material, 5-7 parts of a plasticizer, 140-180 parts of water, and 0-0.6 parts of a preservative; The glue in the soft capsule is selected from any one of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and pregelatinized starch; The plasticizer in the soft capsule is selected from any one of sorbitol, mannitol and glycerol; The preservative in the soft capsule is selected from any one of methyl parahydroxybenzoate, butyl parahydroxybenzoate and ethyl parahydroxybenzoate; The content of chlorogenic acid in the chlorogenic acid self-emulsifying composition is 10 to 150 mg / g.

2. A method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 1, It is characterized in that The preparation method of the chlorogenic acid self-emulsifying composition capsule comprises: encapsulating the chlorogenic acid self-emulsifying composition into a capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.

3. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 2, It is characterized in that The capsule shell is a soft capsule shell, and the preparation method comprises the following steps: The capsule material of the soft capsule is liquefied, and the chlorogenic acid self-emulsifying composition is encapsulated in the soft capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.

4. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 3, It is characterized in that The step of liquefying the capsule material comprises: Heat the water, add the optional preservative according to the formula amount and stir until dissolved, then add the rubber and plasticizer, degas after dissolving.

5. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 4, It is characterized in that The heating temperature is 50-60°C.

6. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 4, It is characterized in that The degassing is performed by a vacuum pump, the degassing pressure is 0.05-0.1 MPa, and the degassing time is 20-30 min.

7. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 3, It is characterized in that The encapsulation method includes a compression method or a dripping method.

8. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 7, It is characterized in that The steps of the pressing method include the following steps: The liquefied rubber liquid is made into a sheet, coated on a rubber wheel, cooled to form a rubber skin, the chlorogenic acid self-emulsifying composition is sprayed out from a nozzle, and a roller mold is used to cut the rubber skin to form a soft capsule.

9. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 8, It is characterized in that The filling amount of the chlorogenic acid self-emulsifying composition is 0.1 to 0.6 mL / grain.

10. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 8, It is characterized in that The cooling temperature is 10-20°C.

11. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 7, It is characterized in that The steps of the dripping method include the following steps: The liquefied gel and chlorogenic acid self-emulsifying composition are dripped out from a nozzle and cooled in an oily coolant to form a spherical soft capsule.

12. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 11, It is characterized in that The filling amount of the chlorogenic acid self-emulsifying composition capsule is 0.1-0.6 mL / capsule.

13. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 11, It is characterized in that The oily coolant includes any one of vegetable oil, silicone oil or liquid paraffin, or a combination of at least two of them.

14. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 11, It is characterized in that The cooling temperature is 10-20°C.

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