CN114504563A - Chlorogenic acid self-emulsifying composition capsule and preparation method thereof - Google Patents
Chlorogenic acid self-emulsifying composition capsule and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention provides a chlorogenic acid self-emulsifying composition capsule and a preparation method thereof. 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 compound formed by chlorogenic acid and a lipid material, an oil phase, an emulsifier and a co-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 provided by the invention has good capsule stability, and the medicine does not migrate in a gelatin hard capsule, a hydroxypropyl methyl cellulose hard capsule and a starch hard capsule.
Description
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to a chlorogenic acid self-emulsifying composition capsule and a preparation method thereof.
Background
Chlorogenic acid is depside composed of caffeic acid and quinic acid, also called caffeotannic acid, and is a phenylpropanoid compound produced by plants in the aerobic respiration process through the shikimic acid pathway. Chlorogenic acid is widely present in plants such as honeysuckle, eucommia leaves, sunflower seeds, oriental wormwood, potted flowers and the like, and has various pharmacological effects of resisting oxidation, bacteria and viruses, reducing blood sugar, reducing blood fat, reducing blood pressure, regulating immunity and the like.
CN110179750A discloses a chlorogenic acid self-emulsifying composition and application thereof, wherein the chlorogenic acid self-emulsifying composition is a uniform oily liquid formed by an oil phase, an emulsifier and a co-emulsifier. However, the prior art does not disclose a suitable capsule filling or preparation method for the chlorogenic acid self-emulsifying composition.
To facilitate oral administration and dosing of liquid drugs, they are typically packaged in capsules made of gelatin, glycerin, or other suitable pharmaceutical materials, alone or in combination, by methods including the infusion method, the compression method, and the filling method.
The dripping method is implemented by a dripping pill machine with a double-layer dripping head, specifically, gelatin solution and oily liquid medicine are respectively contained in a liquid storage tank, the two liquids are sprayed out at different speeds through a concentric tubular double-layer spray head, a certain amount of liquid medicine is wrapped by a certain amount of gelatin solution, and then the gelatin solution is dripped into another immiscible cooling liquid, and the gelatin solution becomes spherical under the action of surface tension after contacting the cooling liquid and is gradually solidified to form the soft capsule.
The pressing method is a method of making the glue solution into films with uniform thickness, placing the liquid medicine between the two films, and pressing the soft capsule by using a steel plate die or a rotary die. At present, the rotary die pressing method is mainly adopted in production (the shape of the die can be oval, spherical or other shapes). The filling method is to directly fill the medicinal liquid into the formed hard capsule made of gelatin or other capsule materials.
CN1449766A discloses a soft capsule preparation of honeysuckle flower and scutellaria root and its preparation method, wherein the capsule preparation contains honeysuckle flower extract, baicalin, honeysuckle flower volatile oil, solvent and stabilizer, and the honeysuckle flower extract contains chlorogenic acid. The Chinese 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 patent application with publication number CN1449766A can not be disintegrated and the content can migrate due to the volatilization of the volatile oil of the active ingredient after being stored for a period of time, and the CN1939408B determines the optimal ratio between the raw materials and the auxiliary materials through exploratory experiments, thereby ensuring the stable quality of the Yinhuang liquid capsule. Just as each of the drugs disclosed in CN1939408B has specific physicochemical properties, a general technical solution cannot be directly applied to the preparation of specific pharmaceutical preparations with specific physicochemical properties without creative experimental studies, and the method for preparing liquid capsules in this patent is not necessarily suitable for other pharmaceutical preparations. Therefore, the development of a liquid capsule preparation method suitable for the chlorogenic acid self-emulsifying composition has important application value.
Disclosure of Invention
The invention aims to provide a chlorogenic acid self-emulsifying composition capsule with good stability, the migration amount of the chlorogenic acid self-emulsifying composition capsule in a soft capsule shell without gelatin is less, and the migration rate of chlorogenic acid in a hydroxypropyl methylcellulose and starch soft capsule is below 3%; migration hardly occurred in the hard gelatin capsule, the hydroxypropyl methyl cellulose capsule and the starch capsule.
The invention unexpectedly discovers that a gelatin soft capsule of the chlorogenic acid self-emulsifying composition can generate a large amount of migration of chlorogenic acid in the preparation process, and the medicine further migrates along with the prolonging of the storage time, so that the medicine content is damaged. The invention provides a method for reducing migration of chlorogenic acid in a chlorogenic acid self-emulsifying composition to a capsule shell in the preparation and storage processes, a chlorogenic acid self-emulsifying composition hard capsule with good stability and a chlorogenic acid self-emulsifying composition soft capsule with good stability.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides a chlorogenic acid self-emulsifying composition capsule, which comprises a capsule shell and a chlorogenic acid self-emulsifying composition wrapped in the capsule shell;
the chlorogenic acid self-emulsifying composition comprises a compound formed by chlorogenic acid and a lipid material, an oil phase, an emulsifier and a co-emulsifier; the capsule shell is a hard capsule or a soft capsule, and the soft capsule does not contain gelatin.
In the invention, the chlorogenic acid self-emulsifying composition has less migration in a soft capsule shell without gelatin and can be stably stored.
In the present invention, the chlorogenic acid mobility is 1- (content of chlorogenic acid in the content after the capsule molding/content of chlorogenic acid in the content before the capsule molding).
Preferably, the soft capsule is prepared from the raw materials of a sizing material, a plasticizer, water and an optional preservative.
Preferably, the preparation raw materials of the soft capsule comprise the following components in parts by weight: 35-45 parts of rubber material, 5-7 parts of plasticizer, 140-180 parts of water and 0-0.6 part of preservative.
In the invention, the weight part of the sizing material in the raw materials for preparing the soft capsule is 35-45 parts, for example, 35 parts, 38 parts, 40 parts, 42 parts or 45 parts.
In the invention, the weight portion of the plasticizer in the raw materials for preparing the soft capsule is 5-7 parts, for example, 5 parts, 5.5 parts, 6 parts, 6.5 parts or 7 parts.
In the invention, the weight part of the water in the raw materials for preparing the soft capsule is 140-180 parts, for example, 140 parts, 150 parts, 160 parts, 170 parts or 180 parts.
In the present invention, the preservative is 0 to 0.6 parts by weight, for example, 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part, or 0.6 part, in the raw materials for preparing the soft capsule.
In the invention, the content of each component of the raw materials of the soft capsule affects the stability of the finally obtained capsule preparation, and the obtained capsule shell has weak elasticity and high hardness under the conditions of increasing the dosage of rubber and reducing the dosage of water, and is difficult to form during preparation. The dosage of the rubber material is reduced, the dosage of the plasticizer is increased, the obtained capsule shell is soft, the thickness is not uniform, and the migration amount of chlorogenic acid is large.
Preferably, the rubber compound comprises a semi-synthetic polymer material and/or a natural polymer material.
Preferably, the semi-synthetic polymer material includes a cellulose-based polymer material.
Preferably, the cellulose-based polymer material comprises any one or a combination of at least two of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, cellulose acetate phthalate, methylcellulose or ethylcellulose.
Preferably, the natural polymer material includes a starch-based polymer material.
Preferably, the starch-based high molecular material comprises natural starch and/or modified starch.
Preferably, the native starch comprises corn starch and/or tapioca starch.
Preferably, the modified starch comprises any one of or a combination of at least two of grafted starch, oxidized starch or pregelatinized starch.
Preferably, the grafted starch comprises hydroxypropyl carboxymethyl starch and/or carboxymethyl starch.
In the invention, the chlorogenic acid self-emulsifying composition has a chlorogenic acid mobility of less than 3% in hydroxypropyl methylcellulose and starch soft capsules.
Preferably, the plasticizer comprises any one of sorbitol, mannitol or glycerol or a combination of at least two thereof.
Preferably, the preservative comprises any one or a combination of at least two of methylparaben, butylparaben or ethylparaben.
Preferably, the hard capsule is prepared from the following raw materials: a gum, a plasticizer, a gelling agent, water, and optionally a preservative.
Preferably, the hard capsule comprises the following raw materials in parts by weight: 100-200 parts of rubber material, 10-14 parts of plasticizer, 12-15 parts of gelling agent, 200-600 parts of water and 0-0.6 part of preservative.
In the hard capsule, the weight part of the sizing material in the preparation raw material of the hard capsule is 100-200 parts, and can be 100 parts, 120 parts, 140 parts, 150 parts, 160 parts, 180 parts or 200 parts, for example.
In the hard capsule, the plasticizer is 10-14 parts by weight, for example, 10 parts, 11 parts, 12 parts, 13 parts or 14 parts by weight.
In the invention, the gel in the raw materials for preparing the hard capsule is 12-15 parts by weight, for example, 12 parts, 13 parts, 14 parts or 15 parts.
In the hard capsule of the present invention, the weight part of the water in the raw materials for preparing the hard capsule is 200 to 600 parts, and may be, for example, 200 parts, 250 parts, 300 parts, 350 parts, 400 parts, 450 parts, 500 parts, 550 parts, 600 parts, or the like.
In the hard capsule, the preservative is 0 to 0.6 part by weight, for example, 0.1 part, 0.2 part, 0.3 part, 0.4 part, 0.5 part or 0.6 part.
Preferably, the size of the hard capsule comprises a semi-synthetic polymer material and/or a natural polymer material.
Preferably, the semi-synthetic polymer material includes a cellulose-based polymer material.
Preferably, the cellulose-based high molecular material is any one or a combination of at least two of hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, cellulose acetate phthalate, methyl cellulose or ethyl cellulose, and is preferably hydroxypropyl methyl cellulose.
Preferably, the natural polymer material includes a starch-based polymer material and/or gelatin.
Preferably, the starch-based high molecular material comprises natural starch and/or modified starch.
Preferably, the native starch comprises corn starch and/or tapioca starch.
Preferably, the modified starch comprises any one of or a combination of at least two of grafted starch, oxidized starch or pregelatinized starch.
Preferably, the grafted starch comprises hydroxypropyl carboxymethyl starch and/or carboxymethyl starch.
In the invention, the chlorogenic acid self-emulsifying composition hardly migrates in a gelatin hard capsule, a hydroxypropyl methyl cellulose hard capsule and a starch hard capsule, which shows that the chlorogenic acid self-emulsifying composition has the best effect when stored in the hard capsule.
Preferably, the plasticizer comprises any one of sorbitol, mannitol or glycerol or a combination of at least two thereof.
Preferably, the gelling agent comprises any one of or a combination of at least two of acacia, carrageenan or pectin.
Preferably, the preservative comprises any one or a combination of at least two of methylparaben, butylparaben or ethylparaben.
Preferably, the capsule shell is a hard capsule, and the specifications of the capsule shell are as follows:
the cap length is 10.8-11.20 mm, for example, 10.8mm, 11.0mm or 11.2 mm;
the length of the body is 18.40-18.80 mm, for example, 18.40mm, 18.60mm or 18.80 mm;
the thickness of the cap wall is 0.085-0.115 mm, for example, 0.085mm, 0.095mm or 0.105mm, 0.115mm, etc.;
the thickness of the body is 0.085 to 0.115mm, and may be, for example, 0.085mm, 0.095mm, 0.105mm, or 0.115 mm.
Preferably, the content of chlorogenic acid in the chlorogenic acid self-emulsifying composition is 5-200 mg/g, and preferably 10-150 mg/g.
The content of chlorogenic acid in the chlorogenic acid self-emulsifying composition is 5-200 mg/g, and can be 5mg/g, 10mg/g, 20mg/g, 40mg/g, 60mg/g, 80mg/g, 100mg/g, 120mg/g, 140mg/g, 150mg/g, 160mg/g, 180mg/g or 200mg/g, and the like.
In a second aspect, the present invention provides a method for preparing a chlorogenic acid self-emulsifying composition capsule according to the first aspect, comprising: encapsulating the chlorogenic acid self-emulsifying composition into a capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.
Preferably, the capsule shell is a hard capsule shell, and the preparation method comprises the following steps:
filling the chlorogenic acid self-emulsifying composition into a hard capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.
Preferably, the temperature of the filled contents is 20 to 25 ℃, and may be, for example, 20 ℃, 21 ℃, 22 ℃, 23 ℃, 24 ℃ or 25 ℃.
Preferably, the capsule shell is a soft capsule shell, and the preparation method comprises the following steps:
liquefying the capsule wall material of the soft capsule, and encapsulating the chlorogenic acid self-emulsifying composition into a soft capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.
Preferably, the step of liquefying the capsule material comprises:
heating water, adding optional preservative according to the formula amount, stirring until the preservative is dissolved, adding the sizing material and the plasticizer, dissolving and defoaming.
Preferably, the heating temperature is 50 to 60 ℃, for example, 30 ℃, 35 ℃, 40 ℃, 45 ℃ or 50 ℃.
Preferably, the defoaming is performed by a vacuum pump, the pressure of the defoaming is 0.05 to 0.1Mpa, such as 0.05Mpa, 0.06Mpa, 0.07Mpa, 0.08Mpa, 0.09Mpa or 0.1Mpa, and the time of the defoaming is 20 to 30min, such as 20min, 21min, 23min, 25min, 27min, 29min or 30 min.
Preferably, the encapsulation method comprises a pressing method or a dropping method.
Preferably, the step of pressing comprises the steps of:
making the liquefied glue solution into sheet, coating on a rubber wheel, cooling to obtain rubber, spraying chlorogenic acid self-emulsifying composition from a nozzle, and rolling and molding to break the rubber to obtain soft capsule.
Preferably, the chlorogenic acid self-emulsifying composition is filled in an amount of 0.1-0.6 mL/particle, for example, 0.1 mL/particle, 0.2 mL/particle, 0.3 mL/particle, 0.4 mL/particle, 0.5 mL/particle, or 0.6 mL/particle.
Preferably, the cooling temperature is 10 to 20 ℃, for example, 10 ℃, 15 ℃, 16 ℃, 17 ℃, 18 ℃, 19 ℃ or 20 ℃.
In the invention, when the soft capsule is prepared by a pressing method, the glue solution is made into films with uniform thickness, then the liquid medicine is placed between the two films, the soft capsule is pressed by a steel plate die or a rotary die, and the shape of the die adopting the rotary die pressing method can be oval, spherical or other shapes.
Preferably, the step of the drop making method comprises the steps of:
dripping the liquefied glue solution and chlorogenic acid self-emulsifying composition from a nozzle, and cooling in oily cooling liquid to form spherical soft capsule.
Preferably, the content of the chlorogenic acid self-emulsifying composition capsule is 0.1-0.6 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;
preferably, the oily cooling liquid comprises any one of vegetable oil, silicone oil or liquid paraffin or a combination of at least two of the above.
Preferably, the cooling temperature is 10 to 20 ℃, for example, 10 ℃, 15 ℃, 16 ℃, 17 ℃, 18 ℃, 19 ℃ or 20 ℃.
The invention relates to a dripping pill machine with a double-layer dripping head for preparing soft capsules by a dripping method, in particular to a dripping pill machine which is characterized in that gelatin solution and oily liquid medicine are respectively contained in a liquid storage tank, the two liquids are sprayed out at different speeds by a concentric tubular double-layer spray head, a certain amount of liquid medicine is wrapped by a certain amount of the gelatin solution and then dripped into another immiscible cooling liquid, and the gelatin solution becomes spherical under the action of surface tension after contacting the cooling liquid and gradually solidifies to form the soft capsules.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention provides a method for reducing migration of chlorogenic acid in a chlorogenic acid self-emulsifying composition to a capsule shell in the preparation and storage processes, a chlorogenic acid self-emulsifying composition hard capsule with good stability and a chlorogenic acid self-emulsifying composition soft capsule with good stability.
(2) The chlorogenic acid self-emulsifying composition capsule provided by the invention has less migration amount in a soft capsule shell without gelatin, and the migration rate of chlorogenic acid in hydroxypropyl methylcellulose and starch soft capsules is below 3%; migration hardly occurred in the hard gelatin capsule, the hydroxypropyl methyl cellulose capsule and the starch capsule. The chlorogenic acid self-emulsifying composition provided by the invention has good stability and low chlorogenic acid mobility.
Drawings
Fig. 1 is a diagram of a finished product of a chlorogenic acid self-emulsifying composition hard capsule in example 1.
FIG. 2 is a diagram of a finished product of the chlorogenic acid self-emulsifying composition gelatin soft capsule in comparative example 1.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
The preparation method of the chlorogenic acid self-emulsifying composition in the embodiment comprises the following steps:
(1) preparation of chlorogenic acid lipid complex
Taking soybean lecithin as a lipid material, feeding chlorogenic acid and the soybean lecithin according to the mass ratio of 1:2.2, adding the chlorogenic acid and the soybean lecithin into a 1L round-bottom flask together, taking absolute ethyl alcohol as a solvent, controlling the concentration of the medicine to be 60mg/mL, standing at room temperature for 15min after the chlorogenic acid and the soybean lecithin are completely dissolved, then carrying out rotary evaporation at 100rpm and 40 ℃ in a rotary evaporator, carrying out reduced pressure drying to remove the absolute ethyl alcohol, and continuing to carry out reduced pressure drying at 100rpm at room temperature for 1h after the ethyl alcohol is evaporated to dryness, thus removing the ethyl alcohol completely. The prepared chlorogenic acid lipid complex is completely compounded, and the compounding rate is over 99 percent.
(2) Preparation of blank self-emulsifying concentrate
Weighing ethyl oleate, an emulsifier (labrasol is taken as an emulsifier) and an auxiliary emulsifier (transcutol HP is taken as an auxiliary emulsifier) according to the mass ratio of 2:5:3, and uniformly stirring and mixing to obtain the blank self-emulsifying concentrated solution.
(3) Preparation of chlorogenic acid self-emulsifying composition
And (3) calculating the drug loading (calculated by chlorogenic acid) by taking 60mg, mixing the chlorogenic acid lipid complex obtained in the step (1) and the blank self-emulsifying concentrated solution obtained in the step (2), and placing the mixture in an air bath oscillator at the temperature of 25 ℃ and the rotation speed of 210 rpm. Obtaining the chlorogenic acid self-emulsifying composition.
Example 1
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the hard capsule shell is prepared from the following raw materials in parts by weight: 100 parts of hydroxypropyl methylcellulose, 10 parts of sorbitol, 12 parts of Arabic gum, 300 parts of water and 0.4 part of methyl p-hydroxybenzoate.
The capsule shell is a hard capsule, and the specifications of the capsule shell are as follows:
the cap length is 11.20mm, the body length is 18.80mm, the cap wall thickness is 0.115mm, and the body wall thickness is 0.115 mm.
Filling the chlorogenic acid self-emulsifying composition into a hard capsule shell, wherein the temperature of the filled content is 25 ℃, the filling amount of the chlorogenic acid self-emulsifying composition is 0.5 mL/capsule, so as to obtain a chlorogenic acid self-emulsifying composition capsule, and the finished product diagram of the chlorogenic acid self-emulsifying composition hard capsule is shown in figure 1.
Example 2
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the hard capsule shell is prepared from the following raw materials in parts by weight: 120 parts of sodium carboxymethylcellulose, 12 parts of sorbitol, 13 parts of Arabic gum, 300 parts of water and 0.5 part of methyl p-hydroxybenzoate.
The preparation method is as in example 1.
Example 3
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the hard capsule shell is prepared from the following raw materials in parts by weight: 120 parts of pregelatinized starch, 14 parts of sorbitol, 15 parts of Arabic gum, 300 parts of water and 0.4 part of methyl p-hydroxybenzoate.
The preparation method is as in example 1.
Example 4
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a hard capsule shell, and the hard capsule shell is prepared from the following raw materials in parts by weight: 100 parts of gelatin, 10 parts of sorbitol, 12 parts of Arabic gum, 300 parts of water and 0.4 part of methyl p-hydroxybenzoate.
The preparation method is as in example 1.
Example 5
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the soft capsule shell is prepared from the following raw materials in parts by weight: 40 parts of hydroxypropyl methylcellulose, 6 parts of glycerol, 150 parts of water and 0.2 part of methyl p-hydroxybenzoate.
The preparation method comprises the following steps:
heating water to 50 ℃, adding methyl p-hydroxybenzoate, stirring until the methyl p-hydroxybenzoate is dissolved, adding hydroxypropyl methyl fiber and sorbitol, dissolving, and defoaming by using a vacuum pump, wherein the defoaming pressure is 0.1Mpa, and the defoaming time is 20 min.
Preparing the liquefied glue solution into a sheet, coating the sheet on a rubber wheel, cooling the sheet at 10 ℃ to form a rubber, spraying the chlorogenic acid self-emulsifying composition from a nozzle, wherein the filling amount of the chlorogenic acid self-emulsifying composition is 0.5 mL/grain, and rolling and pressing the rubber to form the soft capsule.
Example 6
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the soft capsule shell is prepared from the following raw materials in parts by weight: 35 parts of hydroxypropyl methyl cellulose, 6.5 parts of glycerol, 140 parts of water and 0.2 part of methyl p-hydroxybenzoate.
The preparation method comprises the following steps:
heating water to 60 ℃, adding methyl p-hydroxybenzoate, stirring until the methyl p-hydroxybenzoate is dissolved, adding hydroxypropyl methyl fiber and sorbitol, defoaming by using a vacuum pump after the methyl p-hydroxybenzoate and the sorbitol are dissolved, wherein the defoaming pressure is 0.05Mpa, and the defoaming time is 30 min.
Dripping the liquefied glue solution and the chlorogenic acid self-emulsifying composition from a nozzle, cooling in vegetable oil at the temperature of 20 ℃ to obtain the spherical soft capsule, wherein the filling amount of the content of the chlorogenic acid self-emulsifying composition capsule is 0.5 mL/capsule.
Example 7
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the soft capsule shell is prepared from the following raw materials in parts by weight: 45 parts of pregelatinized starch, 7 parts of glycerol, 180 parts of water and 0.2 part of methyl p-hydroxybenzoate.
The preparation method refers to example 5.
Example 8
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the soft capsule shell is prepared from the following raw materials in parts by weight: 40 parts of sodium carboxymethylcellulose, 6 parts of glycerol, 150 parts of water and 0.2 part of methyl p-hydroxybenzoate.
The preparation method is referred to example 5.
Example 9
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the soft capsule shell is prepared from the following raw materials in parts by weight: 25 parts of hydroxypropyl methyl cellulose, 5 parts of glycerol, 140 parts of water and 0.2 part of methyl p-hydroxybenzoate.
The preparation method refers to example 5.
Comparative example 1
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the soft capsule shell is prepared from the following raw materials in parts by weight: 40 parts of gelatin, 6 parts of glycerol, 150 parts of water and 0.2 part of methyl p-hydroxybenzoate.
The preparation method refers to example 5. The diagram of the final product of the chlorogenic acid self-emulsifying composition gelatin soft capsule is shown in figure 2.
Comparative example 2
The embodiment provides a chlorogenic acid self-emulsifying composition capsule, wherein a capsule shell of the chlorogenic acid self-emulsifying composition capsule is a soft capsule shell, and the soft capsule shell is prepared from the following raw materials in parts by weight: 40 parts of gelatin, 6 parts of glycerol, 200 parts of water and 0.2 part of methyl p-hydroxybenzoate.
The preparation method refers to example 5.
Test example 1
The content of chlorogenic acid in the content of 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 ℃, 60% humidity) for 6 months and long-term (4 ℃ refrigerator) standing for 12 months. The test results are shown in table 1:
the determination method comprises the following steps:
and (3) measuring the content of chlorogenic acid in the prepared capsule by adopting an HPLC method. Content of chlorogenic acid/dosage of chlorogenic acid after molding by HPLC.
TABLE 1
The chlorogenic acid self-emulsifying composition in the capsule shells in the embodiments 1 to 4 has no migration of chlorogenic acid in the preparation process, the acceleration condition and the long-term condition. The migration rate 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, carboxymethyl cellulose sodium 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.
The mobility results of chlorogenic acid in examples 5 to 8 show that the chlorogenic acid self-emulsifying composition has a mobility of 1% in the preparation process of hydroxypropyl methylcellulose soft capsules, a mobility of 2% under an accelerated condition, and a mobility of 1% under a long-term condition; the mobility in the preparation process of the pregelatinized starch soft capsule is 2%, the mobility under an accelerated condition is 3%, and the mobility under a long-term condition is 2%; in the preparation process of the sodium carboxymethylcellulose soft capsule under the accelerated condition, the mobility is 2%, the mobility is 3% and the mobility under the long-term condition is 2%; the result shows that the chlorogenic acid self-emulsifying composition can be stored for a long time in hydroxypropyl methylcellulose soft capsules, pregelatinized starch soft capsules and sodium carboxymethyl cellulose soft capsules.
From the results of the mobility of chlorogenic acids in examples 5 and 9, it can be seen that the amount of the gum material is reduced, the relative content of glycerin and water in the capsule shell is increased, the capsule shell is soft and has uneven thickness, and the chlorogenic acid has a large migration amount.
As can be seen from the comparison of the mobility results of chlorogenic acid in example 5 and comparative examples 1-2, the mobility of the chlorogenic acid self-emulsifying composition under the acceleration condition of the soft capsule shell containing gelatin is 16%; the result shows 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 can adsorb active ingredients in the chlorogenic acid self-emulsifying composition and influence the stability of the chlorogenic acid self-emulsifying composition.
In conclusion, the invention finds that the migration amount of the chlorogenic acid self-emulsifying composition in a soft capsule shell without gelatin is less, and the migration rate of the chlorogenic acid in a hydroxypropyl methylcellulose and starch soft capsule is below 3%; migration hardly occurred in the hard gelatin capsule, hydroxypropyl methylcellulose capsule and starch capsule, indicating that the chlorogenic acid self-emulsifying composition stored in the hard capsule has the best effect, and the starch soft capsule and hydroxypropyl methylcellulose soft capsule have the next lowest effect, and the gelatin soft capsule has the worst effect.
The chlorogenic acid self-emulsifying composition capsule provided by the invention has the advantages that the capsule shell can protect the main component from the action of oxygen and water molecules in air, the capsule shell can be stored for a long time, the stability of the medicine is improved, and the content is liquid and is convenient to absorb.
The applicant declares that the above description is only a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and it should be understood by those skilled in the art that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are within the scope and disclosure of the present invention.
Claims (10)
1. The chlorogenic acid self-emulsifying composition capsule is characterized by comprising a capsule shell and a chlorogenic acid self-emulsifying composition wrapped in the capsule shell;
the chlorogenic acid self-emulsifying composition comprises a compound formed by chlorogenic acid and a lipid material, an oil phase, an emulsifier and a co-emulsifier; the capsule shell is a hard capsule or a soft capsule, and the soft capsule does not contain gelatin.
2. The chlorogenic acid self-emulsifying composition capsule according to claim 1, wherein the soft capsule is prepared from a sizing material, a plasticizer, water and optionally a preservative;
preferably, the preparation raw materials of the soft capsule comprise the following components in parts by weight: 35-45 parts of sizing material, 5-7 parts of plasticizer, 140-180 parts of water and 0-0.6 part of preservative;
preferably, the rubber compound comprises a semi-synthetic polymer material and/or a natural polymer material;
preferably, the semi-synthetic polymer material includes a cellulose-based polymer material;
preferably, the cellulose-based high molecular material comprises any one or a combination of at least two of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, cellulose acetate phthalate, methylcellulose or ethylcellulose;
preferably, the natural polymer material comprises a starch-based polymer material;
preferably, the starch-based high molecular material comprises natural starch and/or modified starch;
preferably, the native starch comprises corn starch and/or tapioca starch;
preferably, the modified starch comprises any one of or a combination of at least two of grafted starch, oxidized starch or pregelatinized starch;
preferably, the grafted starch comprises hydroxypropyl carboxymethyl starch and/or carboxymethyl starch;
preferably, the plasticizer comprises any one or a combination of at least two of sorbitol, mannitol, or glycerol;
preferably, the preservative comprises any one or a combination of at least two of methylparaben, butylparaben or ethylparaben.
3. The chlorogenic acid self-emulsifying composition capsule according to claim 1 or 2, wherein the raw materials for preparing the hard capsule comprise: a sizing, a plasticizer, a gelling agent, water, and optionally a preservative;
preferably, the hard capsule comprises the following raw materials in parts by weight: 100-200 parts of rubber material, 10-14 parts of plasticizer, 12-15 parts of gelling agent, 200-600 parts of water and 0-0.6 part of preservative;
preferably, the size of the hard capsule comprises a semi-synthetic polymer material and/or a natural polymer material;
preferably, the semi-synthetic polymer material includes a cellulose-based polymer material;
preferably, the cellulose-based high molecular material is any one or a combination of at least two of hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, cellulose acetate phthalate, methyl cellulose or ethyl cellulose, preferably hydroxypropyl methyl cellulose;
preferably, the natural polymer material comprises a starch polymer material and/or gelatin;
preferably, the starch-based high molecular material comprises natural starch and/or modified starch;
preferably, the native starch comprises corn starch and/or tapioca starch;
preferably, the modified starch comprises any one of or a combination of at least two of grafted starch, oxidized starch or pregelatinized starch;
preferably, the grafted starch comprises hydroxypropyl carboxymethyl starch and/or carboxymethyl starch;
preferably, the plasticizer comprises any one or a combination of at least two of sorbitol, mannitol, or glycerol;
preferably, the gelling agent comprises any one or a combination of at least two of acacia, carrageenan or pectin;
preferably, the preservative comprises any one or a combination of at least two of methylparaben, butylparaben or ethylparaben;
preferably, the capsule shell is a hard capsule, and the specifications of the capsule shell are as follows: the cap length is 10.8-11.20 mm, the body length is 18.40-18.80 mm, the cap wall thickness is 0.085-0.115 mm, and the body wall thickness is 0.085-0.115 mm.
4. The chlorogenic acid self-emulsifying composition capsule according to any one of claims 1 to 3, wherein the content of chlorogenic acid in the chlorogenic acid self-emulsifying composition is 5 to 200mg/g, preferably 10 to 150 mg/g.
5. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to any one of claims 1 to 4, which comprises the following steps: encapsulating the chlorogenic acid self-emulsifying composition into a capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.
6. The method for preparing a chlorogenic acid self-emulsifying composition capsule according to claim 5, wherein the capsule shell is a hard capsule shell, the method comprises the following steps:
filling the chlorogenic acid self-emulsifying composition into a hard capsule shell to obtain a chlorogenic acid self-emulsifying composition capsule;
preferably, the temperature of the filled contents is 20-25 ℃.
7. The method for preparing the chlorogenic acid self-emulsifying composition capsule according to claim 5, wherein the capsule shell is a soft capsule shell, and the method comprises the following steps:
liquefying the capsule wall material of the soft capsule, and encapsulating the chlorogenic acid self-emulsifying composition into a soft capsule shell to obtain the chlorogenic acid self-emulsifying composition capsule.
8. The method for preparing a chlorogenic acid self-emulsifying composition capsule according to claim 7, wherein the step of liquefying the capsule wall material comprises:
heating water, adding an optional preservative according to the formula amount, stirring until the preservative is dissolved, adding a sizing material and a plasticizer, dissolving and defoaming;
preferably, the heating temperature is 50-60 ℃;
preferably, the defoaming is carried out by adopting a vacuum pump, the defoaming pressure is 0.05-0.1 Mpa, and the defoaming time is 20-30 min;
preferably, the encapsulation method comprises a pressing method or a dropping method.
9. The method for preparing a chlorogenic acid self-emulsifying composition capsule according to claim 8, wherein the step of pressing comprises the steps of:
preparing the liquefied glue solution into a sheet, coating the sheet on a rubber wheel, cooling the sheet into rubber, spraying the chlorogenic acid self-emulsifying composition from a nozzle, and rolling and pressing the rubber to break the rubber to form a soft capsule;
preferably, the filling amount of the chlorogenic acid self-emulsifying composition is 0.1-0.6 mL/grain;
preferably, the cooling temperature is 10-20 ℃.
10. The method for preparing a chlorogenic acid self-emulsifying composition capsule according to claim 8, wherein the dropping method comprises the following steps:
dripping the liquefied glue solution and chlorogenic acid self-emulsifying composition from a nozzle, and cooling in an oily cooling liquid to form a spherical soft capsule;
preferably, the filling amount of the content of the chlorogenic acid self-emulsifying composition capsule is 0.1-0.6 mL/granule;
preferably, the oily cooling liquid comprises any one of vegetable oil, silicone oil or liquid paraffin or a combination of at least two of the vegetable oil, the silicone oil and the liquid paraffin;
preferably, the cooling temperature is 10-20 ℃.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110169955A (en) * | 2019-07-05 | 2019-08-27 | 陕西中医药大学 | A kind of production method of the soft capsule shell based on modified starch |
| CN110179750A (en) * | 2019-06-17 | 2019-08-30 | 四川九章生物科技有限公司 | A kind of chlorogenic acid self-emulsifying composition and application thereof |
| CN112336698A (en) * | 2019-08-09 | 2021-02-09 | 南京科宁检测科技有限公司 | Rapidly disintegrating vaginal soft capsule composition and preparation method thereof |
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| CN110179750A (en) * | 2019-06-17 | 2019-08-30 | 四川九章生物科技有限公司 | A kind of chlorogenic acid self-emulsifying composition and application thereof |
| CN110169955A (en) * | 2019-07-05 | 2019-08-27 | 陕西中医药大学 | A kind of production method of the soft capsule shell based on modified starch |
| CN112336698A (en) * | 2019-08-09 | 2021-02-09 | 南京科宁检测科技有限公司 | Rapidly disintegrating vaginal soft capsule composition and preparation method thereof |
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