CN112716911A - Caffeine microcapsule, preparation method thereof and compound paracetamol and alkyl amine preparation - Google Patents
Caffeine microcapsule, preparation method thereof and compound paracetamol and alkyl amine preparation 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
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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
- A61K31/13—Amines
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/37—Digestive system
- A61K35/413—Gall bladder; Bile
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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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
Abstract
The invention relates to the technical field of pharmaceutical preparations, in particular to a caffeine microcapsule, a preparation method thereof and a compound paracetamol and amantadine hydrochloride preparation. The caffeine microcapsule comprises a core material, a first wall material wrapping the core material and a second wall material wrapping the first wall material; the core material is caffeine, the first wall material is octenyl succinate starch, and the second wall material is carboxymethyl cellulose. The invention utilizes proper wall materials to carry out microencapsulation on the caffeine, delays the absorption of the caffeine in a human body, thereby furthest shortening the difference of the peak reaching time of the blood concentration of the caffeine and chlorpheniramine maleate, and better relieving the lethargy effect caused by the chlorpheniramine maleate. In addition, caffeine has strong bitter taste, and the direct addition of caffeine to the medicine results in bitter taste and poor taste. The caffeine microcapsule provided by the invention is added with the modified starch, so that the caffeine raw material is wrapped to a certain extent, the bitterness of the medicine is reduced, and the feeling of taking the medicine by a patient is better.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a caffeine microcapsule, a preparation method thereof and a compound paracetamol and alkyl amine preparation.
Background
The anti-cold medicine is a common medicine in daily life of people, is mostly a compound preparation in the market, is suitable for various colds, and has quick response and long efficacy. Most of them contain ingredients of antihistamine drugs chlorpheniramine maleate or diphenhydramine, which can relieve allergic symptoms of cold patients such as sneezing, rhinorrhea, lacrimation and the like, but because they can inhibit central nerves through blood brain barrier, the anti-cold drugs all show the side effects of sleepiness and sleepiness after taking, and cause inconvenience to life after taking.
Caffeine, a xanthine alkaloid compound, a central stimulant, can alleviate sleepiness caused by chlorpheniramine maleate to some extent, temporarily drive drowsiness and restore energy. Can enhance the antipyretic and analgesic effects of acetaminophen contained in the anti-cold medicine. Can also be used for resisting central inhibition of antihistamine chlorphenamine maleate, and relieving side effects of central inhibitor such as asthenia and lethargy. Therefore, the caffeine is added into the anti-cold medicine, which not only can assist and strengthen the treatment effect, but also can achieve the effect of relieving the side effect of sleepiness.
Gankang (compound paracetamol and amantadine hydrochloride tablet) is a common cold-resistant medicine, and comprises the main components of paracetamol, amantadine hydrochloride, artificial bezoar, chlorphenamine maleate and caffeine. Chlorpheniramine maleate serving as a first-generation antihistamine medicine is mainly used for skin mucosa allergy, can relieve symptoms such as watery nasal discharge, nasal obstruction, sneeze and the like, and has obvious lethargy as an adverse reaction. Caffeine in the medicine can resist central inhibition of chlorphenamine maleate, but the time of the two acting is different. The caffeine is absorbed rapidly and completely in gastrointestinal tract after oral administration, and the blood concentration reaches the peak value within about 15-60 minutes, and the peak value can last to 120 minutes. The oral blood concentration of chlorpheniramine maleate can reach the peak value after 3 hours. Therefore, after the patient takes the medicine for about 3 hours, the concentration of the chlorpheniramine maleate in the blood reaches the peak value, the adverse reaction of fatigue and sleepiness begins to aggravate, the peak value of the blood concentration of the caffeine is missed at the moment, so that the caffeine cannot well play a central excitation role, and the adverse reaction of the medicine lethargy is obvious.
Disclosure of Invention
In view of the above, the present invention provides a caffeine microcapsule, a preparation method thereof, and a compound paracetamol preparation. The invention delays the absorption of caffeine in human body by microencapsulation, thereby shortening the time difference of peak arrival time of blood concentration of chlorphenamine maleate and better relieving the lethargy effect caused by chlorphenamine maleate.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a caffeine microcapsule, which comprises a core material, a first wall material wrapping the core material and a second wall material wrapping the first wall material; the core material is caffeine, the first wall material is octenyl succinate starch, and the second wall material is carboxymethyl cellulose.
The caffeine microcapsule prepared by taking coffee as a core material, octenyl succinate starch as a first wall material and carboxymethyl cellulose as a second wall material properly delays the absorption of caffeine in a human body, thereby maximally shortening the difference of peak reaching time of blood concentration of chlorphenamine maleate and better relieving the lethargy caused by chlorphenamine maleate.
In some embodiments, the mass ratio of caffeine to the first wall material and the second wall material is (5-25): (1-5): (1-5). In some embodiments, the mass ratio is specifically 5:1:1, 5:5:5, or 25:1: 1.
The invention also provides a preparation method of the caffeine microcapsule, which comprises the following steps:
adding an organic solution of a core material into a first wall material aqueous solution to obtain a suspension;
dispersing, homogenizing and spray drying the suspension in sequence to obtain a caffeine wet capsule;
and uniformly mixing the caffeine wet capsule with the second wall material aqueous solution, and drying to obtain the caffeine microcapsule.
In some embodiments, the organic solution of the core material is an ethanol solution of the core material; the mass ratio of the core material to the ethanol is (5-25): (25-60). In some embodiments, the mass ratio of the core material to the ethanol is: 5:25, 5:60, 25: 60.
In some embodiments, the mass ratio of the first wall material to the water in the first wall material aqueous solution is 1-5: 10. In some embodiments, the mass ratio of the first wall material to the water is 5:10 or 1: 10. During preparation, the first wall material aqueous solution is prepared by firstly heating water to 80-85 ℃, adding the first wall material for dissolution, and cooling to room temperature.
In some embodiments, the mass ratio of the second wall material to the water in the second wall material aqueous solution is 1-5: 10. In some embodiments, the mass ratio of the second wall material to water is 5:10 or 1: 10. When preparing the first wall material aqueous solution, firstly heating water to 80-85 ℃, adding the first wall material for dissolving, and cooling to room temperature to obtain a second wall material aqueous solution.
In the present invention, the homogenization includes a first homogenization and a second homogenization.
In some embodiments, the pressure of the first homogenization is between 20MPa and 30MPa and the pressure of the second homogenization is between 2MPa and 10 MPa. In some embodiments, the first homogenization pressure is 20MPa or 30MPa and the second homogenization pressure is 2MPa or 10 MPa.
In some embodiments, the air inlet temperature of the spray drying is 180 ℃ to 200 ℃, and the air outlet temperature is 80 ℃ to 100 ℃. In some embodiments, the air inlet temperature of the spray drying is 180 ℃ or 200 ℃, and the air outlet temperature is 80 ℃ or 100 ℃.
In order to verify whether the peak time of the blood concentration of the caffeine and the chlorphenamine maleate in the body is consistent or not in the compound paracetamol and amantadine hydrochloride preparation prepared by the caffeine microcapsule, the invention adopts a high performance liquid chromatography to measure the blood concentration of the caffeine and the chlorphenamine maleate in the body at different times. The curve shows that the two components reach the highest value of blood concentration about 3 hours after being taken, and mouse experiments can verify that the peak time of the blood concentration of the two components of caffeine and chlorphenamine maleate is basically consistent after being taken, which indicates that after the caffeine is prepared into microcapsules, the compound paracetamol and amantadine hydrochloride tablets are prepared, and the adverse reaction of lethargy caused by chlorphenamine maleate can be effectively eliminated.
Based on the effects, the invention also provides the application of the caffeine microcapsule in preparing the anti-cold medicine containing chlorpheniramine maleate.
In some embodiments, the anti-cold drug containing chlorpheniramine maleate is a compound paracetamol and amantadine hydrochloride preparation.
The invention also provides a compound paracetamol and amantadine hydrochloride preparation, which comprises the caffeine microcapsule or the caffeine microcapsule prepared by the preparation method.
In some embodiments, the compound paracetamol and amantadine hydrochloride formulation further comprises acetaminophen, amantadine hydrochloride, artificial bezoar, chlorpheniramine maleate and pharmaceutically acceptable excipients in addition to the caffeine microcapsules of the present invention.
The invention does not have special requirements on the types of pharmaceutically acceptable auxiliary materials, and a person skilled in the art can select the proper types of auxiliary materials according to actual conditions to prepare various formulations such as tablets, capsules, granules and the like according to the preparation method of the conventional preparation in the field.
The compound paracetamol and amantadine hydrochloride preparation provided by the invention has no special limitation on the dosage of active ingredients contained in the preparation, can be prepared according to the dosage proportion disclosed by the prior art, and can also be used for adjusting each active ingredient. In the specific embodiment of the invention, the following components are used:
the caffeine microcapsule provided by the invention utilizes the appropriate wall material to carry out microencapsulation on the caffeine, and delays the absorption of the caffeine in a human body, thereby furthest shortening the difference of the peak time of blood drug concentration with chlorpheniramine maleate, solving the problem that the peak time of blood drug concentration is different after the caffeine and the chlorpheniramine maleate are taken, and relieving the lethargy effect caused by the chlorpheniramine maleate. The caffeine which originally reaches the peak value of blood concentration within 15-60 min is enabled to play a specific slow release role through the caffeine microcapsule technology, the peak value of the blood concentration is pushed to about 3 hours after the caffeine microcapsule technology is taken, so that the caffeine and the chlorpheniramine maleate simultaneously reach the time point of strongest drug effect, and the caffeine microcapsule technology can play a role of exciting the central nervous system when the chlorpheniramine maleate plays the drug effect, thereby effectively reducing or even eliminating the adverse reaction of tiredness and sleepiness, and greatly facilitating the life, study and work of patients. In addition, caffeine has strong bitter taste, and the direct addition of caffeine to the medicine results in bitter taste and poor taste. The caffeine microcapsule provided by the invention is added with the modified starch, so that the caffeine raw material is wrapped to a certain extent, the bitterness of the medicine is reduced, and the feeling of taking the medicine by a patient is better.
Drawings
FIG. 1 shows the chlorpheniramine maleate dosing curves for the formulation of example 1;
FIG. 2 shows the caffeine bolus time profile of the formulation of example 1;
FIG. 3 shows the chlorpheniramine maleate dosing curves for the formulation of comparative example 1;
FIG. 4 shows the caffeine bolus time curve for the comparative example 1 formulation;
FIG. 5 shows the chlorpheniramine maleate dosing curves for the formulation of comparative example 2;
figure 6 shows the caffeine bolus profile for the formulation of comparative example 2.
Detailed Description
The invention provides a caffeine microcapsule, a preparation method thereof and a compound paracetamol and amantadine hydrochloride preparation. Those skilled in the art can modify the process parameters appropriately to achieve the desired results with reference to the disclosure herein. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
The test materials adopted by the invention are all common commercial products and can be purchased in the market.
The invention is further illustrated by the following examples:
example 1 preparation of microcapsules of the invention
Heating water to 80 ℃, adding wall material octenyl succinate starch for dissolving, and cooling to room temperature, wherein the mass ratio of the wall material to the water is 5:10, so as to obtain a first wall material aqueous solution;
heating water to 80 ℃, adding a wall material of carboxymethyl cellulose for dissolving, and cooling to room temperature, wherein the mass ratio of the wall material to the water is 5:10, so as to obtain a second wall material aqueous solution;
mixing the core material (caffeine) and ethanol according to a mass ratio of 5:25 to obtain an ethanol solution of the core material;
the mass ratio of the caffeine to the first wall material and the second wall material is 5:1: 1;
and adding the ethanol solution of the core material into the first wall material aqueous solution to form a suspension.
Homogenizing the suspension after dispersing under 20MPa for the first time and 10MPa for the second time. Then spray drying is carried out, the air inlet temperature is 180 ℃, the air outlet temperature is 100 ℃, and the caffeine microcapsule wet capsule is obtained.
And uniformly mixing the caffeine microcapsule wet bag with a second wall material aqueous solution, carrying out secondary embedding, and removing water in a system by using a centrifugal drying agent to obtain the caffeine microcapsule.
Example 2 preparation of microcapsules of the invention
Heating water to 80 ℃, adding wall material octenyl succinate starch for dissolving, and cooling to room temperature, wherein the mass ratio of the wall material to the water is 5:10, so as to obtain a first wall material aqueous solution;
heating water to 80 ℃, adding a wall material of carboxymethyl cellulose for dissolving, and cooling to room temperature, wherein the mass ratio of the wall material to the water is 1:10, so as to obtain a second wall material aqueous solution;
mixing the core material with ethanol according to the mass ratio of 5:60 to obtain an ethanol solution of the core material;
the mass ratio of the caffeine to the first wall material and the second wall material is 5:5: 5;
and adding the ethanol solution of the core material into the first wall material aqueous solution to form a suspension.
Homogenizing the suspension after dispersing under 20MPa for the first time and 10MPa for the second time. Then spray drying is carried out, the air inlet temperature is 180 ℃, the air outlet temperature is 100 ℃, and the caffeine microcapsule wet capsule is obtained.
And uniformly mixing the caffeine microcapsule wet bag with a second wall material aqueous solution, carrying out secondary embedding, and removing water in a system by using a centrifugal drying agent to obtain the caffeine microcapsule.
Example 3 preparation of microcapsules of the invention
Heating water to 80 ℃, adding wall material octenyl succinate starch for dissolving, and cooling to room temperature, wherein the mass ratio of the wall material to the water is 1:10, so as to obtain a first wall material aqueous solution;
heating water to 80 ℃, adding a wall material of carboxymethyl cellulose for dissolving, and cooling to room temperature, wherein the mass ratio of the wall material to the water is 5:10, so as to obtain a second wall material aqueous solution;
mixing the core material (caffeine) and ethanol according to the mass ratio of 25:60 to obtain an ethanol solution of the core material;
the mass ratio of the caffeine to the first wall material and the second wall material is 25:1: 1;
and adding the ethanol solution of the core material into the first wall material aqueous solution to form a suspension.
Homogenizing the suspension after dispersing under 20MPa for the first time and 10MPa for the second time. Then spray drying is carried out, the air inlet temperature is 180 ℃, the air outlet temperature is 100 ℃, and the caffeine microcapsule wet capsule is obtained.
And uniformly mixing the caffeine microcapsule wet bag with a second wall material aqueous solution, carrying out secondary embedding, and removing water in a system by using a centrifugal drying agent to obtain the caffeine microcapsule.
EXAMPLE 4 preparation of Compound Paracetamol and Alkylamine tablet
Prepared using the caffeine microcapsules of example 1.
The specific prescription is as follows:
the process flow is as follows:
sieving and pulverizing acetaminophen, amantadine hydrochloride, caffeine microcapsule, artificial bezoar and chlorphenamine maleate, mixing with adjuvants such as filler, granulating by wet method, adding adjuvants such as lubricant, mixing, and tabletting to obtain compound paracetamol and amantadine hydrochloride tablet.
Test examples blood concentration measurement test
In order to verify the slow release effect of the caffeine microcapsule, the experiment of measuring the blood concentration at different times by adopting a high performance liquid chromatography is adopted, and a pharmaceutical time curve is drawn. Therefore, whether the peak time of the blood concentration of the caffeine microcapsule and the chlorpheniramine maleate in vivo is consistent or not is verified.
Collecting samples: healthy male mice were selected as 40 and randomly divided into 5 groups of 8 mice each (each mouse was used as a blood sampling point, each group was a drug timing curve). Mice were fasted for 12h before the experiment without water deprivation. Administering at a dose of 1mg/kg by intragastric administration, collecting blood from eyeball 1, 2, 3, 4, 5, 7, 9, and 11h after administration, placing in heparinized test tube, centrifuging at 3000r/min for 10min, and separating plasma.
High performance liquid chromatography conditions: a Kromasil C18 chromatography column; mobile phase: acetonitrile-water (containing 0.5% phosphoric acid, 0.4% triethylamine) ═ 10: 90; flow rate: 1.0 mL/min; detection wavelength: 264 nm; column temperature: at 30 ℃.
Experimental setup control and experimental groups (example 1 treatment group). Wherein, the control group comprises a control treatment group, a comparative example 1 treatment group and a comparative example 2 treatment group.
Control treatment group: the caffeine reference substance and the chlorpheniramine maleate reference substance are respectively precisely weighed and prepared into 10 mu g/mL reference substance solutions by using 0.1mol/L hydrochloric acid solution.
Example 1 treatment group: the compound paracetamol and amantadine hydrochloride tablets in the example 4 are respectively prepared into 10 mu g/mL test solution of the example 1 by using 0.1mol/L hydrochloric acid solution.
Comparative example 1 treatment group: the preparation method of the caffeine microcapsule has the advantages that the second wall material wall is modified starch, and other steps and parameters are the same as those of the preparation method of the microcapsule and the preparation method of the compound paracetamol and amantadine hydrochloride preparation. The prepared tablets were prepared into 10. mu.g/mL test solutions of comparative example 1 using 0.1mol/L hydrochloric acid solution, respectively.
Comparative example 2 treatment group: the step of secondary embedding by using a second wall material is omitted in the preparation method of the caffeine microcapsule, and other steps and parameters are the same as the preparation method of the microcapsule and the preparation method of the compound paracetamol and amantadine hydrochloride preparation. The prepared tablets were prepared into 10. mu.g/mL test solutions of comparative example 2 using 0.1mol/L hydrochloric acid solution, respectively.
Plasma sample treatment: precisely absorbing 0.5mL of a plasma sample, putting the plasma sample into a 10mL centrifuge tube, adding 5mL of ethyl acetate, uniformly mixing for 3min by vortex, centrifuging for 5min, taking 4mL of supernatant, and drying in a water bath at 40 ℃ by nitrogen. Re-dissolving the residue with 200 μ L mobile phase, vortex for 1min, and centrifuging at 13000r/min for 5 min.
Respectively and precisely sucking 20 μ L of the above reference solution and each sample solution, analyzing with high performance liquid chromatograph, calculating the concentrations of caffeine and chlorphenamine maleate in blood plasma according to external standard method, and drawing pharmaceutical time curve according to the blood concentration at different time points. The chlorpheniramine maleate dosing curves for the formulation of example 1 are shown in figure 1, and the caffeine dosing curves are shown in figure 2; the chlorpheniramine maleate dosing curve for the formulation of comparative example 1 is shown in fig. 3, and the caffeine dosing curve is shown in fig. 4; the chlorpheniramine maleate dosing curves for the formulation of example 1 are shown in figure 5 and the caffeine dosing curves are shown in figure 6.
The time curve of taking the medicine shows that the two components of the caffeine and the chlorpheniramine maleate in the treatment group in the example 1 reach the highest value of blood concentration about 3 hours after being taken, and a mouse experiment can verify that the peak arrival time of the blood concentration of the two components of the caffeine and the chlorpheniramine maleate after being taken is basically consistent, which indicates that the adverse reaction of preventing sleepiness brought by the chlorpheniramine maleate can be achieved by adding the compound paracetamol and amantadine hydrochloride tablets after the caffeine is prepared into microcapsules. The difference between the peak time of the blood concentration of the two components of the treatment group of the comparative example 1 and the treatment group of the comparative example 2 is large, which indicates that the adverse reaction effect of using the microcapsules of the comparative example 1 and the comparative example 2 to resist the lethargy brought by the chlorpheniramine maleate is not obvious.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that it is obvious to those skilled in the art that various modifications and improvements can be made without departing from the principle of the present invention, and these modifications and improvements should also be considered as the protection scope of the present invention.
Claims (10)
1. The caffeine microcapsule is characterized by comprising a core material, a first wall material wrapping the core material and a second wall material wrapping the first wall material; the core material is caffeine, the first wall material is octenyl succinate starch, and the second wall material is carboxymethyl cellulose.
2. The caffeine microcapsule according to claim 1, wherein the mass ratio of the caffeine to the first and second wall materials is (5 to 25): (1-5): (1-5).
3. A process for the preparation of caffeine microcapsules according to claim 1 or 2, which comprises:
adding an organic solution of a core material into a first wall material aqueous solution to obtain a suspension;
dispersing, homogenizing and spray drying the suspension in sequence to obtain a caffeine wet capsule;
and uniformly mixing the caffeine wet capsule with the second wall material aqueous solution, and drying to obtain the caffeine microcapsule.
4. The production method according to claim 3, wherein the organic solution of the core material is an ethanol solution of the core material; the mass ratio of the core material to the ethanol is (5-25): (25-60).
5. The preparation method according to claim 3, wherein the mass ratio of the first wall material to the water in the aqueous solution of the first wall material is (1-5): 10.
6. The preparation method according to claim 3, wherein the mass ratio of the second wall material to water in the second wall material aqueous solution is (1-5): 10.
7. The production method according to claim 3, wherein the homogenization includes a first homogenization and a second homogenization; the pressure of the first homogenizing is 20 MPa-30 MPa, and the pressure of the second homogenizing is 2 MPa-10 MPa.
8. The preparation method according to claim 3, wherein the inlet air temperature of the spray drying is 180-200 ℃, and the outlet air temperature is 80-100 ℃.
9. Use of the caffeine microcapsules according to claim 1 or 2 or the caffeine microcapsules prepared by the preparation method according to any one of claims 3 to 8 in the preparation of anti-cold drugs containing chlorpheniramine maleate.
10. A compound paracetamol and amantadine hydrochloride preparation, which is characterized by comprising the caffeine microcapsule according to claim 1 or 2 or the caffeine microcapsule prepared by the preparation method according to any one of claims 3 to 8.
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