CN108542909B - Aspirin phospholipid solidified composition, preparation method thereof and pharmaceutical preparation - Google Patents
Aspirin phospholipid solidified composition, preparation method thereof and pharmaceutical preparation Download PDFInfo
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Abstract
The invention belongs to the technical field of pharmaceutical preparations. The invention discloses an aspirin phospholipid solidified composition, which is prepared from aspirin, phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor; the invention discloses a preparation method of an aspirin phospholipid solidified composition, which comprises the steps of aspirin crushing, mixture preparation, mixture solidification and the like; the invention also discloses an aspirin phospholipid pharmaceutical preparation which is a tablet, capsule or granular preparation prepared from the aspirin phospholipid solidified composition. After the aspirin and the phospholipid form a compound, the release of the aspirin in the stomach can be reduced, the adverse reaction of the gastrointestinal tract of the medicine can be obviously reduced, the medication compliance can be improved, the medicine solubility can be improved, the medicine absorption can be enhanced, the medicine bioavailability can be improved, and the adverse reaction of the medicine can be reduced; the preparation method of the aspirin phospholipid curing composition has simple process and good reproducibility, and can realize modern commercial production.
Description
Technical Field
The invention relates to the technical field of medicinal preparations, in particular to an aspirin phospholipid solidified composition, a preparation method thereof and a medicinal composition.
Background
Aspirin (Aspirin), also known as acetylsalicylic acid, is one of three classic drugs in history, has obvious effect and low price as an antipyretic analgesic with long history, is still the most widely applied antipyretic analgesic and anti-inflammatory drug to date, and is a standard preparation for comparing and evaluating other drugs. Pharmacological research shows that aspirin can permanently inactivate COX-1 activity and inhibit platelet function, has no dose-related effect and can quickly achieve the inhibition effect at an extremely low concentration (nmol/L), namely, has a definite anticoagulation effect, so that the aspirin can be used as a medicament for preventing thrombus. The Chinese expert consensus recommends that the long-term aspirin application dose is 75-100 mg/day in the first-level prevention, and 75-150 mg/day in the second-level prevention.
The maximum toxic and side effects of aspirin are that gastrointestinal tract mucosal erosion, bleeding, ulcer and the like are easily caused. Besides relieving pain and fever, aspirin is required to be taken for a long time when used for treating rheumatic fever, arthritis, antithrombotic diseases and other diseases, and the incidence of toxic and side effects is increased. Although people improve the dosage form, such as adding suppository to avoid the contact of the medicine with the gastrointestinal tract, the medicine is very inconvenient to take; if the enteric-coated preparation is prepared, although the incidence of toxic and side effects is reduced to a certain extent, the leakage phenomenon occurs in part of tablets in the stomach, so that the stomach is stimulated and the gastric mucosa is damaged; if the content of free salicylic acid in the enteric-coated tablet is high, salicylic acid poisoning reaction can be caused, and the problem is still not solved fundamentally.
Disclosure of Invention
In order to solve the problem of salicylic acid poisoning of aspirin preparations, the invention provides an aspirin phospholipid solidified composition which can reduce gastrointestinal irritation, protect gastric mucosa and solve the problem of salicylic acid poisoning;
the present invention provides a process by which aspirin phospholipid solidified compositions can be prepared;
the invention also provides a medicinal preparation prepared from the aspirin phospholipid solidified composition.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
an aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor in a weight ratio of 1: 1-3: 1-4: 0.1-0.4: 0.05-0.2; the adsorbent is at least one of microcrystalline cellulose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, dry starch, sodium carboxymethyl starch, silicon dioxide, crospovidone or pregelatinized starch; the viscosity regulator is at least one of tricaprylin, caprylic/capric triglyceride, caprylic/capric/linoleic triglyceride, propylene glycol dicaprylate/dicaprate or butanediol dicaprylate/dicaprate; the hydrolysis inhibitor is at least one of tartaric acid, oxalic acid, malic acid, citric acid, ascorbic acid or succinic acid.
The liquid phospholipid has protective effect on gastrointestinal mucosa, and can increase viscosity of mucus layer together with mucus glycoprotein; slow down H+The bicarbonate secreted by the gastric epithelium has sufficient time to neutralize the mucus layer; in addition, a hydrophobic layer can be formed on the surface of the mucous membrane, so that the protein in the mucus and the cells is prevented from being hydrolyzed.
After the aspirin and the liquid phospholipid form a compound, the release of the aspirin in the stomach can be reduced, the adverse reaction of the gastrointestinal tract of the medicine can be obviously reduced, the dissolving performance of the medicine can be improved, the medicine absorption can be enhanced, the bioavailability of the medicine can be improved, and the adverse reaction of the medicine can be reduced.
The adsorbent can solidify liquid phospholipid, and the composition is more stable and suitable for modern commercial production.
Preferably, the liquid phospholipid is at least one of phosal 35SB, phosal 53MCT, phosal 75SA, phosal 50PG, phosal 50SA +, soya lecithin or sunflower lecithin.
Preferably, the content of phosphatidylcholine in the liquid phospholipid is 25-75 wt%.
Preferably, the adsorbent is at least one of microcrystalline cellulose, croscarmellose sodium, silicon dioxide, crospovidone, or pregelatinized starch.
Preferably, the silica is amino-modified mesoporous silica.
Preferably, the amino modified mesoporous silica is prepared by preparing 80 parts by weight of ammonium nitrate aqueous solution with the pH value of 6.0-6.5, dissolving 0.4-0.9 part by weight of trimethyl ammonium bromide in the ammonium nitrate aqueous solution, dissolving and stirring, naturally defoaming, preheating the solution to 70-85 ℃, adding 4-5 parts by weight of ethyl orthosilicate, stirring at 70-85 ℃ for 2-3 minutes, injecting alkali reaction liquid along the tangential direction of the liquid surface at a linear speed of 1-2 m/s while stirring to make the pH value of the solution 9-10, stirring at 70-85 ℃ for 1-2 hours to prepare mesoporous silica mixed liquid, concentrating the mesoporous silica mixed liquid to 40-50 parts by weight, adjusting the pH value to 7-8, adding 0.1-0.3 part by weight of disodium glutamate, stirring at 30-40 ℃ for 2-3 hours, finally, filtering, washing with water and washing with ethanol to obtain amino modified mesoporous silica; the alkali reaction solution is an ammonia water solution with ammonia content of 15-20 wt% added with 5-10 wt% of sodium hydroxide and 0.1-0.5 wt% of sorbitol fatty acid ester.
The irritation of aspirin to the stomach is mainly caused by the fact that the aspirin preparation is acidic after being dissolved out of the stomach to cause damage to the gastric mucosa, and particularly, the free salicylic acid generated after the aspirin preparation is dissolved out of the stomach causes salicylic acidosis; although the invention has adopted liquid phospholipid to coat aspirin and has slowed down H+The rate of entry into the gastric environment, but it is still not completely free of H+The product after the adsorbent is combined with the aspirin liquid phospholipid is adsorbed and solidified by the adsorbent, and the adsorbent can be in omnibearing contact with the aspirin liquid phospholipid combined product, so that the adsorbent can be subjected to amino modification to obtain H in the aspirin liquid phospholipid combined product+On release H+The amino group of the branch on the surface of the adsorbent is neutralized in advance, so that H entering the stomach after aspirin is hydrolyzed is further reduced+So as to better protect the stomach and reduce the damage of aspirin to the stomach. Meanwhile, the adsorbent adopts amino modified mesoporous silicon dioxide, the mesoporous silicon dioxide has strong adsorption effect, the mesoporous structure is suitable for adsorbing the aspirin liquid phospholipid combined product in the invention, the adsorbent can be firmly combined with the aspirin liquid phospholipid combined product, and the released H can be better treated+。
When the amino modified mesoporous silica is prepared, the mesoporous silica is prepared firstly, and then the surface of the silica is modified by using amino acid salt. Preparing mesoporous silicon dioxide by adopting a method of hydrolyzing ethyl orthosilicate, firstly dissolving a template agent of cetyltrimethylammonium bromide in an acidic ammonium nitrate solution, then adding ethyl orthosilicate, and then introducing an alkaline solution into the solution to realize hydrolysis in an alkaline environment; the amino modification stage is carried out immediately after the mesoporous silicon dioxide is prepared, and the amino modification stage is carried out by concentrating, adjusting the pH value and then adding amino acid. The alkaline solution in the invention adopts a mixed solution composed of sodium hydroxide, sorbitol fatty acid ester and ammonia water, only low-concentration ammonia water can be adopted due to high-temperature treatment, a small amount of sodium hydroxide is added for adjusting the pH value of the solution, in addition, foam can bring adverse effects in the whole process, and simultaneously, a large amount of bubbles can be generated when stirring or injecting the alkaline solution due to the surface activity of a template agent of cetyl trimethylammonium bromide, and the sorbitol fatty acid ester is added for defoaming. The alkaline solution is added in an injection mode, so that the effect of auxiliary stirring can be achieved, and the purpose of enabling the alkaline solution to be mixed more uniformly in the vertical direction can be achieved, so that hydrolysis of the tetraethoxysilane is integrally uniform instead of being carried out in a layered mode, the external appearance of the prepared mesoporous silica is guaranteed to be more uniform, and the internal pore channels are also more uniform.
Preferably, the viscosity modifier is tricaprylin.
Preferably, the hydrolysis inhibitor is at least one of tartaric acid and citric acid.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
The preparation method of the aspirin phospholipid composition mainly comprises two parts, namely preparation of an aspirin and liquid phospholipid mixture and solidification of the mixture, wherein the mixture is solidified, so that the composition is more stable, and is more suitable for storage and transportation and modern commercial production.
Preferably, in step a, aspirin is comminuted to D 9010 to 30 μm.
Preferably, in step b, the hydrolysis inhibitor is dispersed in the viscosity modifier and then added to the liquid phospholipid.
An aspirin phospholipid pharmaceutical preparation is tablet, capsule or granule prepared from aspirin phospholipid solidified composition.
Therefore, the invention has the following beneficial effects:
(1) the existing preparation process of the phospholipid compound is that solid phospholipid and medicine are dissolved in organic solution, then the organic solution is removed, and finally the phospholipid compound is prepared into different dosage forms according to the requirement; the process can not avoid the problem of organic residue, and the explosion prevention of organic solvent, the safety protection of production workers and the discharge of waste water and waste gas need to be paid attention to during production. The preparation method of the aspirin phospholipid curing composition has the advantages of no organic residue, small environmental pollution, simple process and good reproducibility, and can realize modern commercial production.
(2) After the aspirin and the phospholipid form a compound, the release of the aspirin in the stomach can be reduced, the adverse reaction of the gastrointestinal tract of the medicine can be obviously reduced, and the medication compliance is improved;
(3) the aspirin phospholipid solidified composition can improve the solubility of the medicine, enhance the medicine absorption, improve the bioavailability of the medicine and reduce the adverse reaction of the medicine;
drawings
FIG. 1 is a graph showing the in vitro cumulative dissolution rates of examples 1 to 9.
Detailed Description
The technical solution of the present invention will be further described with reference to the following embodiments.
It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the present invention, all the equipments and materials are commercially available or commonly used in the industry, and the methods in the following examples are conventional in the art unless otherwise specified.
Example 1
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 810g, the adsorbent is 940g, the viscosity regulator is 179.9g, and the hydrolysis inhibitor is 74.8 g;
the liquid phospholipid is phosal 35SB, the content of phosphatidylcholine in the liquid phospholipid is 50 wt%, the adsorbent is silicon dioxide, the viscosity regulator is tricaprylin, and the hydrolysis inhibitor is citric acid.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9020 μm for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid medicinal preparation is capsule prepared from aspirin phospholipid solidified composition.
Example 2
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein 270g of aspirin, 810g of liquid phospholipid, 540g of adsorbent, 79.9g of viscosity regulator and 44.8g of hydrolysis inhibitor are added; the liquid phospholipid is phosal 35SB, the content of phosphatidylcholine in the liquid phospholipid is 50 wt%, the adsorbent is amino modified mesoporous silica, the viscosity regulator is tricaprylin, and the hydrolysis inhibitor is citric acid;
the amino modified mesoporous silica is prepared by preparing 80 weight parts of ammonium nitrate aqueous solution with the pH value of 6.0, dissolving 0.6 weight part of hexadecyl trimethyl ammonium bromide in the ammonium nitrate aqueous solution, naturally defoaming after dissolving and stirring, then the above solution was preheated to 80 ℃ followed by addition of 4 parts by weight of ethyl orthosilicate and stirring at 80 ℃ for 3 minutes, then injecting the alkali reaction solution along the tangential direction of the liquid level at the linear velocity of 1m/s while stirring to ensure that the pH value of the solution is 10, stirring for 2 hours at 80 ℃ to prepare mesoporous silica mixed liquor, concentrating the mesoporous silica mixed liquor to 40 parts by weight, adjusting the pH value of the mesoporous silica mixed liquor to 7, adding 0.2 part by weight of disodium glutamate into the mesoporous silica mixed liquor, stirring and treating for 2 hours at 35 ℃, and finally filtering, washing with water and washing with ethanol to prepare amino modified mesoporous silica; the alkali reaction solution was an aqueous ammonia solution containing 16 wt% of ammonia to which 5wt% of sodium hydroxide and 0.2 wt% of a sorbitol fatty acid ester were added.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9020 μm for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid medicinal preparation is capsule prepared from aspirin phospholipid solidified composition.
Example 3
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 810g, the adsorbent is 940g, the viscosity regulator is 259.8g and the hydrolysis inhibitor is 74.8 g;
the liquid phospholipid is prepared from phosal 35SB and phosal 53MCT in a weight ratio of 1: 1, the content of phosphatidylcholine in the liquid phospholipid is 50 wt%, the adsorbent is silicon dioxide, the viscosity regulator is tricaprylin, and the hydrolysis inhibitor is citric acid.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9020 μm for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid pharmaceutical preparation is tablet, capsule or granule prepared from aspirin phospholipid solidified composition.
Example 4
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 810g, the adsorbent is 940g, the viscosity regulator is 259.8g and the hydrolysis inhibitor is 74.8 g;
the liquid phospholipid is prepared from phosal 35SB, phosal 53MCT and phosal 75SA in a weight ratio of 1: 1: 1, the content of phosphatidylcholine in the liquid phospholipid is 50 wt%, the adsorbent is silicon dioxide, the viscosity regulator is tricaprylin, and the hydrolysis inhibitor is citric acid.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9020 μm for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid medicinal preparation is capsule prepared from aspirin phospholipid solidified composition.
Example 5
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 810g, the adsorbent is 1100g, the viscosity regulator is 179.9g, and the hydrolysis inhibitor is 74.8 g;
the liquid phospholipid is phosal 35SB, the content of phosphatidylcholine in the liquid phospholipid is 50 wt%, and the adsorbent is microcrystalline cellulose and silicon dioxide according to the weight ratio of 1: 1, the viscosity regulator is glyceryl tricaprylate, and the hydrolysis inhibitor is tartaric acid.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9020 μm for use;
b) putting liquid phospholipid into a container, heating in water bath, stirring, simultaneously vacuumizing and degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in the water bath and vacuumizing environment after degassing is finished, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid medicinal preparation is prepared from aspirin phospholipid solidified composition and is in the form of capsule.
Example 6
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 810g, the adsorbent is 110g, the viscosity regulator is 179.9g, and the hydrolysis inhibitor is 74.8 g;
the liquid phospholipid is phosal 35SB, the content of phosphatidylcholine in the liquid phospholipid is 50 wt%, and the adsorbent is prepared from microcrystalline cellulose, silicon dioxide and crospovidone according to a weight ratio of 3: 2: 6, the viscosity regulator is tricaprylin, and the hydrolysis inhibitor is tartaric acid.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9020 μm for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment at the same time, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid medicinal preparation is capsule prepared from aspirin phospholipid solidified composition.
Example 7
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 810g, the adsorbent is 110g, the viscosity regulator is 179.9g, and the hydrolysis inhibitor is 74.8 g;
the liquid phospholipid is prepared from phosal 50PG and phosal 50SA + according to the weight ratio of 1: 1, the content of phosphatidylcholine in the liquid phospholipid is 50 wt%, and the adsorbent is silicon dioxide and pregelatinized starch in a weight ratio of 6: 5, the viscosity regulator is caprylic/capric triglyceride, and the hydrolysis inhibitor is oxalic acid.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9020 μm for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment at the same time, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid pharmaceutical preparation is tablet, capsule or granule prepared from aspirin phospholipid solidified composition.
Example 8
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 810g, the adsorbent is 810g, the viscosity regulator is 81g, and the hydrolysis inhibitor is 40.5 g;
the liquid phospholipid is prepared from soybean lecithin and sunflower lecithin in a weight ratio of 1: 1, the content of phosphatidylcholine in the liquid phospholipid is 25 wt%, and the adsorbent is prepared from microcrystalline cellulose, silicon dioxide, crospovidone and pregelatinized starch according to the weight ratio of 7: 10: 2: 5, the viscosity regulator is caprylic acid/capric acid/linoleic acid triglyceride, and the hydrolysis inhibitor is malic acid and ascorbic acid according to the weight ratio of 1: 1, in a mixture of the components.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D 9010 μm for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid pharmaceutical preparation is tablet prepared from aspirin phospholipid solidified composition.
Example 9
An aspirin phospholipid solidified composition is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor, wherein the aspirin is 810g, the liquid phospholipid is 2430g, the adsorbent is 3240g, the viscosity regulator is 324g, and the hydrolysis inhibitor is 162 g;
the liquid phospholipid is prepared from phosal 35SB and soybean soft phospholipid according to the weight ratio of 1: 1, the content of phosphatidylcholine in the liquid phospholipid is 75 wt%;
the adsorbent is prepared from low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, dry starch and sodium carboxymethyl starch in a weight ratio of 1: 1: 1: 1 mixture composed by weight ratio;
the viscosity regulator is prepared from glycerol tricaprylate, propylene glycol dicaprylate/dicaprate and butanediol dicaprylate/dicaprate in a weight ratio of 1: 1: 1;
the hydrolysis inhibitor is prepared from tartaric acid, malic acid, citric acid and succinic acid according to a weight ratio of 1: 1: 1: 1, in a mixture of the components.
A preparation method of an aspirin phospholipid solidified composition comprises the following steps:
a) pulverizing aspirin to its D90Is 30 mu m for standby;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment at the same time, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture; wherein the hydrolysis inhibitor is dispersed into the viscosity regulator and then added;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
An aspirin phospholipid medicinal preparation is a granular preparation obtained by directly packaging an aspirin phospholipid solidified composition.
Performance testing of the invention:
(1) in vitro dissolution assay:
the dissolution method comprises the following steps: referring to the second method of the dissolution method in Chinese pharmacopoeia, the rotating speed is 75rpm, 900ml of pH6.8 phosphate buffer solution containing 10 millimole cholic acid; the cumulative dissolution rates of examples 1 to 9 are shown in Table 1.
TABLE 1 in vitro cumulative dissolution rates of examples 1-9
The dissolution result shows that the in vitro dissolution conditions of samples in different examples are not obviously different, the dissolution rate in 30min is more than 85 percent, and the preparation belongs to a quick dissolution preparation.
(2) SD rat gastrointestinal tract irritation test
The samples of example 1 and example 7 were selected for the SD rat gastrointestinal tract stimulation test.
TABLE 2SD rat gastrointestinal irritation test samples
| Sample (I) | Specification of | Manufacturer of the product |
| Physiological saline | —— | Baxter Healthcare (Shanghai) Co.,Ltd. |
| Example 1 sample | 81 mg/granule | Zhejiang Hengchung biological medicine Co., Ltd |
| Example 8 sample | 81 mg/granule | Zhejiang Hengchung biological medicine Co., Ltd |
| Aspirin tablet | 500 mg/tablet | SHANDONG XINHUA PHARMACEUTICAL Co.,Ltd. |
| Aspirin |
100 mg/granule | Mayne PharmaP International Pty Ltd. |
The experimental method comprises the following steps: 50 healthy SD mice with qualified quarantine are divided into 5 groups, and each group comprises 10 mice. Animals were weighed and administered orally for 14 days at a dose of 300 mg/kg. After the administration is finished, animals are fasted and are not forbidden to be watered overnight, general anatomical observation is carried out, main organs are weighed, and pathological sections are made on the stomach. The degree of gastric injury in SD mice after the experiment is shown in Table 3.
TABLE 3 statistics of the degree of gastric injury in SD mice after the experiment
Note: 0-normal; 1-mild; 2-moderate; 3-Severe.
Compared with the normal saline control group, the aspirin tablet, the sample in the example 1, the sample in the example 7 and the aspirin enteric capsule group have mild gastric injury, and the aspirin tablet group has obvious gastric injury after the sample in the example 2 and the aspirin enteric capsule group are treated. Statistical analysis is carried out on the injury conditions by adopting a rank sum test, and compared with the sample group of the example 2 and the sample group of the example 8, the aspirin enteric capsule group has P more than 0.05 and has no statistical difference; compared with the aspirin tablet group, P is less than 0.05, and the statistical difference is obtained.
The results indicate that capsules and tablets of aspirin phospholipid compositions can reduce gastrointestinal irritation.
It will be understood that modifications and variations can be made by persons skilled in the art in light of the above teachings and all such modifications and variations are intended to be included within the scope of the invention as defined in the appended claims.
Claims (9)
1. An aspirin phospholipid solidifying composition characterized by:
the aspirin-phospholipid composite material is prepared from aspirin, liquid phospholipid, an adsorbent, a viscosity regulator and a hydrolysis inhibitor in a weight ratio of 1: 1-3: 1-4: 0.1-0.4: 0.05-0.2;
the adsorbent is at least one of microcrystalline cellulose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, dry starch, sodium carboxymethyl starch, silicon dioxide, crospovidone or pregelatinized starch;
the viscosity regulator is at least one of tricaprylin, caprylic/capric triglyceride, caprylic/capric/linoleic triglyceride, propylene glycol dicaprylate/dicaprate or butanediol dicaprylate/dicaprate;
the hydrolysis inhibitor is at least one of tartaric acid, oxalic acid, malic acid, citric acid, ascorbic acid or succinic acid;
the content of phosphatidylcholine in the liquid phospholipid is 25-75 wt%.
2. An aspirin phospholipid solidifying composition according to claim 1, characterized in that:
the liquid phospholipid is at least one of phosal 35SB, phosal 53MCT, phosal 75SA, phosal 50PG, phosal 50SA +, soybean lecithin or sunflower lecithin.
3. An aspirin phospholipid solidifying composition according to claim 1, characterized in that:
the adsorbent is at least one of microcrystalline cellulose, croscarmellose sodium, silicon dioxide, crospovidone or pregelatinized starch.
4. An aspirin phospholipid solidifying composition according to claim 1, characterized in that:
the viscosity regulator is tricaprylin.
5. An aspirin phospholipid solidifying composition according to claim 1, characterized in that:
the hydrolysis inhibitor is at least one of tartaric acid and citric acid.
6. A process for preparing an aspirin phospholipid solidified composition according to claim 1, 2, 4 or 5, characterized by the steps of:
a) pulverizing aspirin for use;
b) placing liquid phospholipid in a container, heating in water bath, stirring, and simultaneously vacuumizing and degassing; after degassing, adding a hydrolysis inhibitor, a viscosity regulator and aspirin in a water bath and vacuum environment, and then uniformly stirring to obtain an aspirin liquid phospholipid mixture;
c) adding the adsorbent into a wet granulator, and then adding the aspirin liquid phospholipid mixture for wet granulation to obtain the aspirin phospholipid composition.
7. The method of claim 6, wherein the phospholipid-solidified composition comprises:
in said step a, aspirin is pulverized to D thereof9010 to 30 μm.
8. The method of claim 6, wherein the phospholipid-solidified composition comprises:
in the step b, the hydrolysis inhibitor is firstly dispersed into the viscosity regulator and then added into the liquid phospholipid.
9. An aspirin phospholipid pharmaceutical preparation, which is characterized in that: which is a tablet, capsule or granule formulation made from the aspirin phospholipid solidified composition of claim 1 or 2 or 3 or 4 or 5.
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| CN1543358A (en) * | 2000-12-19 | 2004-11-03 | �ÿ���˹ϵͳ��ѧ���»� | Nsaid formulations comprising lecithin oils for protecting the gastrointestinal tract and providing enhanced therapeutic activity |
| US20100173876A1 (en) * | 2000-12-19 | 2010-07-08 | The Board Of Regents Of The University Of Texas System | Oil-based nsaid compositions and methods for making and using same |
| CN103957888A (en) * | 2011-09-29 | 2014-07-30 | PLx制药公司 | Ph dependent carriers for targeted release of pharmaceuticals along the gastrointestinal tract, compositions therefrom, and making and using same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1543358A (en) * | 2000-12-19 | 2004-11-03 | �ÿ���˹ϵͳ��ѧ���»� | Nsaid formulations comprising lecithin oils for protecting the gastrointestinal tract and providing enhanced therapeutic activity |
| US20100173876A1 (en) * | 2000-12-19 | 2010-07-08 | The Board Of Regents Of The University Of Texas System | Oil-based nsaid compositions and methods for making and using same |
| CN103957888A (en) * | 2011-09-29 | 2014-07-30 | PLx制药公司 | Ph dependent carriers for targeted release of pharmaceuticals along the gastrointestinal tract, compositions therefrom, and making and using same |
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Address after: 310000 room 1109, building 2, Wanjing Lake Central West area, Xiasha street, Qiantang new area, Hangzhou, Zhejiang Patentee after: ZHEJIANG HAICHANG BIO-TECH CO.,LTD. Address before: 311100 22 / F, building 4, No. 1500, Wenyi West Road, Yuhang District, Hangzhou City, Zhejiang Province Patentee before: ZHEJIANG HAICHANG BIO-TECH CO.,LTD. |