CN107233322A - It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency - Google Patents
It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency Download PDFInfo
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- CN107233322A CN107233322A CN201710306805.2A CN201710306805A CN107233322A CN 107233322 A CN107233322 A CN 107233322A CN 201710306805 A CN201710306805 A CN 201710306805A CN 107233322 A CN107233322 A CN 107233322A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
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- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A61K9/20—Pills, tablets, discs, rods
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- A61K9/2004—Excipients; Inactive ingredients
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- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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Abstract
Progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency and preparation method thereof are treated the invention discloses a kind of.The treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency include the component of following parts by weight：100 parts of trinosin, 200 400 parts of sodium alginate, 100 200 parts of hydroxypropyl methyl cellulose, 0 800 parts of Gentran 40,50 200 parts of sodium carboxymethyl starch, 50 100 parts of lauryl sodium sulfate, 15 30 parts of superfine silica gel powder, 15 30 parts of magnesium stearate.Trinosin is prepared into inclusion compound by preparation method of the present invention using sodium alginate swelling techniques, then further by main ingredient inclusion compound prepared composition discrete piece.The dissolubility increase of product trinosin of the present invention, dissolution rate are higher, and disintegration time limited shortens, and bioavilability is improved, and improves curative effect.Its preparation method technique is simple, and production cost is low, consumes energy low, easily realizes industrialized production.
Description
Technical field
The invention belongs to medicine field, it is related to a kind of pharmaceutical preparation and preparation method thereof, it is more particularly to a kind of to be used to control
Treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency and preparation method thereof.
Background technology
Trinosin (ATP), is a kind of coenzyme.Trinosin is nucleotide derivative, be body from
The anakinetomer that body is produced, is the center that energy i (in vivo) is utilized and stored, participates in body fat, protein, sugar, nucleic acid and core
The metabolism of thuja acid.When body absorption, secretion, contraction of muscle and the biochemical synthetic reaction of progress etc. need energy, atriphos
Adenosine diphosphate (ADP) and phosphate are resolved into, is given off energy simultaneously, is played an important role in vital movement.Three phosphorus
Adenosine monophosphate disodium can penetrate blood cerebrospinal fluid barrier, can improve the stability and reconstruction ability of nerve cell membranous structure, promote
The regrowth of nervous process.Clinically be used for heart failure, myocarditis, myocardial infarction, cerebral arteriovenous malformation, coronary sclerosis,
Acute poliomyelitis, progressive myatrophy illness.Modern study shows that trinosin can suppress in animal experiment
The slow flow of calcium ions of long response time fiber, blocks or delays the forward conduction in atrioventricular nodal reentry approach, and heavy dose is also possible to resistance
Forward direction and conduct retrograde disconnected or that delay bypass；Also there is the vagal effect of of short duration strong enhancing in addition, thus can terminate
Arrhythmia cordis caused by atrioventricular nodal reentry and bypass foldback mechanism.
Because having above-mentioned good drug effect, trinosin is made into bulk drug, tablet, parenteral solution etc., wherein three
AMP disodium piece is the chemical drugs preparation being made using trinosin as raw material, trinosin piece record in
《National drug standards chemicals provincial standard rises national standard》9th, standard No. be WS-10001- (HD-0787)-
2002, specification is 20mg/ pieces, is mainly used in progressive myatrophy, cerebral hemorrhage sequelae, cardiac insufficiency, myocardosis and liver
The auxiliary treatment of inflammation etc..
Tablet, the parenteral solution being made in spite of above-mentioned trinosin, but due to the reasons such as technology of preparing, triphosphoric acid
Adenosine disodium piece has that disintegration time length, dissolution rate is low, absorption is poor and bioavilability, directly after taking
Influence the effect for the treatment of.In addition, the patient such as progressive myatrophy, cerebral hemorrhage sequelae, cardiac insufficiency, myocardosis and hepatitis
Long-term treatment is needed, injection is such as used for a long time and is inconvenient, treatment cost is high, the shortcoming of making patients' financial burden weight.And
And presently commercially available trinosin preparation is generally tablet, disintegration and work compared with, it is impossible to promptly mitigate slow patient symptom.Cause
This, it is necessary to prepare that disintegration rate is very fast, dissolution preferably, the treatment progressive myatrophy that is easy to absorb, bioavilability is higher,
The pharmaceutical preparation of cerebral hemorrhage sequelae, cardiac insufficiency, to meet a variety of demands that clinical treatment and family use.
Dispersible tablet (Dispersible tablets) is also known as water dispersion tablet (Water dispersible tablets), is
The tablet to form homogeneous viscous suspension can be disintegrated rapidly by referring to chance water.For conventional tablet, dispersible tablet absorbs fast, biological
Availability is high, and adverse reaction is small, can reduce excitant of the medicine to intestines and stomach.Dispersible tablet is convenient to take, can swallow, chew,
Containing sucking, it can also put and individually be taken after disperseing in water or with fruit juice, milk with taking, be especially suitable for old, children and to swallow solid difficult
Patient.Therefore, trinosin for main ingredient be used for treat chronic gastritis, the medicine of hyperhydrochloria makes dispersible tablet,
The shortcoming of trinosin piece presence is overcome, a variety of demands that clinical treatment and family use are met.
The content of the invention
The disintegration time length of the invention existed for existing trinosin piece, dissolution rate are low, absorption is poor and raw
Thing availability is relatively low, it is impossible to promptly play drug effect so as to which there is provided a kind of disintegration rate the problems such as quickly mitigating slow patient symptom
It hurry up, dissolution is good, decentralization is high, be easy to absorb, bioavilability is high, rapid-action, treatment progressive myatrophy convenient to take, brain
Bleeding sequelae, pharmaceutical preparation of cardiac insufficiency and preparation method thereof, solve trinosin at present on the market
The above mentioned problem that piece is present.Present invention treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency, are carried
High disintegration rate and bioavilability, so as to improve curative effect, present invention treatment progressive myatrophy, cerebral hemorrhage sequelae,
The preparation method of the pharmaceutical preparation of cardiac insufficiency, technique is simple, and production cost is low, consumes energy low, easily realizes industrialized production.
In order to solve the above technical problems, the present invention is achieved by the following technical solutions：
It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency, by following parts by weight
Component：100 parts of trinosin, 200-400 parts of sodium alginate, 100-200 parts of hydroxypropyl methyl cellulose, glucan
400-800 parts, 50-200 parts of sodium carboxymethyl starch, 50-100 parts of lauryl sodium sulfate, 15-30 parts of superfine silica gel powder, stearic acid
15-30 parts of magnesium.
It is described above treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency, most preferably preferably by
The component of following parts by weight：100 parts of trinosin, 300 parts of sodium alginate, 150 parts of hydroxypropyl methyl cellulose, Portugal gather
600 parts of sugar, 125 parts of sodium carboxymethyl starch, 75 parts of lauryl sodium sulfate, 20 parts of superfine silica gel powder, 20 parts of magnesium stearate.
Treatment progressive myatrophy described above, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency are prepared into scattered
Piece.
More than one described treatment progressive myatrophies, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency are prepared into
The method of dispersible tablet, comprises the following steps：
T1：Following components is weighed by weight：100 parts of trinosin, 200-400 parts of sodium alginate, hydroxypropyl
100-200 parts of methylcellulose, 0-800 parts of Gentran 40,50-200 parts of sodium carboxymethyl starch, lauryl sodium sulfate 50-100
Part, 15-30 parts of superfine silica gel powder, 15-30 parts of magnesium stearate, cross 100 mesh sieves, standby；
T2：Prepare trinosin inclusion compound；
T3：Taking hydroxypropyl methyl cellulose to be dissolved in the ethanol of 400-800 parts 65%, that hydroxypropyl methyl cellulose is made is dilute
Ethanol solution；
T4：It is another to take glucan, sodium carboxymethyl starch, lauryl sodium sulfate and the lower preparation gained Adenosine triphosphate of step T2
Glycosides disodium inclusion compound is added in mixer, is stirring evenly and then adding into hydroxypropyl methyl cellulose Diluted Alcohol solution, 10-15 points of stirring
Softwood is made in clock；
T5：Take the softwood being made to put in oscillating granulator, cross 20 mesh sieve wet granulations, wet granular is put in drying box and dried,
Take out, put and 50 mesh sieves progress whole grain is crossed in pelletizing machine, obtain dry particl after whole grain；
T6：Dry particl after grain is rounded to put in high efficient mixer, plus superfine silica gel powder and magnesium stearate, mix 30 minutes, be made
Treat tabletting trinosin mixed powder；
T7：Take trinosin mixed powder to put in tablet press machine, be pressed into plain piece, produce.
The preparation method of trinosin inclusion compounds is under step T2 described above：
S1：Take load weighted sodium alginate to put in material-compound tank, add water 600-800 parts be heated at 45-65 DEG C heating make it is molten
It is swollen complete；
S2：Be slowly added into trinosin under the conditions of maintaining the temperature at 45 DEG C -65 DEG C, insulated and stirred 1-2h, put to
Taken out after room temperature, be dried in vacuo 8-12h, crushed, crossed 80 mesh sieves, obtain trinosin inclusion compound.
Further, the vacuum drying vacuum is -0.06Mpa to -0.09Mpa, drying temperature under step S2
For 50 DEG C -65 DEG C, drying time is 8h-12h, and the mixing speed is 40rpm-60rpm, gained main ingredient inclusion compound control moisture
Content≤6%.
The drying temperature of the drying steps is 60 DEG C -80 DEG C under step T5 described above, and drying time is 10h-
12h, the dry particl controls moisture≤6%.
The beneficial effects of the invention are as follows：
1. the present invention overcomes the poorly water-soluble that existing disodium adenosine triphosphate tablet is present, disintegration and slower, the dissolution that works
Degree is low, and bioavilability is relatively low, it is impossible to promptly play drug effect so as to the problems such as quickly mitigating slow patient symptom.It is disintegrated product
Speed is significantly improved, and dissolution preferably, absorbs very fast, and energy quick acting, bioavilability is high, is conducive to improving curative effect, and clothes
With conveniently.
2. product drug dissolution of the present invention reaches more than 90%, it is significantly increased, has significantly than former formulation (sugar coated tablet)
Beneficial to the bioavilability for improving medicine, adverse reaction is reduced.
3. the present invention is with PVPP, glucan, carboxyrnethyl starch sodium, lauryl sodium sulfate, hydroxypropyl methyl fiber
Element, superfine silica gel powder gelatin, magnesium stearate, without sugared part, are conducive to the long-term taking of hyperglycemic patients, overcome original as auxiliary material
The shortcomings of formulation (sugar coated tablet) is unfavorable for hyperglycemic patients long-term taking.
4. the inventive method technique is simple, production equipment is operated without particular/special requirement, easily, consume energy it is low, time saving, be produced into
This is low, easily realizes industrialized production.
Embodiment
Although this specification is drawn a conclusion by particularly pointing out and claims of the present invention being clearly claimed, should
This believes that following explanation is better understood with the present invention.
As used herein, word " preferably " and variant refer to that this hair of specific beneficial effect can be provided in certain circumstances
Bright embodiment.However, other embodiments can also be preferred under identical or other environment.In addition, one
Or it is useless that the detailed description of multiple preferred embodiments, which is not offered as other embodiments, and it is not intended to from scope of the invention
Exclude other embodiments.
First, formulation conditions are screened
1. the selection of disintegrant
The species and consumption of disintegrant are most important to the disintegration of dispersible tablet, result of extraction, are the factors for first having to consider.
The disintegrant commonly used in dispersible tablet has sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, PVPP, cross-linked carboxymethyl fine
Plain sodium of dimension etc..Using hydroxypropyl methyl cellulose as adhesive, superfine silica gel powder:Magnesium stearate (1:1) it is glidant, respectively to 7%
PVPP, 7% sodium carboxymethyl starch, 7% low-substituted hydroxypropyl cellulose, 7% Ac-Di-Sol, 4 kinds of disintegrations
Agent carries out Selection experiment, overall merit is carried out by evaluation index of outward appearance, disintegration time limited and dispersing uniformity, to determine dispersible tablet
In optimal disintegrant species.It the results are shown in Table 1.
The optimization test result table of the disintegrant of table 1
It was found from the result of the test in table 1：It is smooth using sodium carboxymethyl starch tablet surface made from disintegrant, and disintegration
Time limit and dispersing uniformity are preferable, therefore present invention selection sodium carboxymethyl starch is disintegrant.The present invention continues to optimize carboxymethyl
The consumption of sodium starch, result of the test is shown in Table 2.
The sodium carboxymethyl starch consumption of table 2 investigates result table
It was found from the result of the test in table 2：The present invention is piece made from disintegrant using 5%-11% sodium carboxymethyl starches
Agent surface is smooth, and disintegration time limited and dispersing uniformity are preferable, thus the present invention selection sodium carboxymethyl starch as disintegrant when
Consumption is the 5%-11% for accounting for recipe quantity.
2. adhesive is selected
The present invention compared for the tabletting again of compressing dry granulation, wet granulation, and compressing dry granulation is bad using conventional tablet machines effect, right
Equipment requirement is high, therefore the present invention uses wet granulation tabletting again.Dispersible tablet uses the particle that hydrophilic adhesive is made, surface tool
Moisture is easily moistened after hydrophily, tabletting, is penetrated into, beneficial to disintegration of tablet.Water, 65% ethanol solution, 25% hydroxyl have been investigated in experiment
65% ethanol solution of propyl methocel, 65% ethanol solution of 35% hydroxypropyl methyl cellulose make adhesive, to make
Grain situation, tablet appearance, disintegration time limited and dispersing uniformity are that evaluation index carries out overall merit, the results are shown in Table 3.
The adhesive of table 3 investigates result table
It was found from the result of the test in table 3：The present invention uses 65% ethanol solution system of 25% hydroxypropyl methyl cellulose
Grain situation, tablet appearance, disintegration time limited and dispersing uniformity effect are best, therefore invention adhesives select 25% hydroxypropyl methyl
65% ethanol solution of cellulose.The present invention continues to optimize the consumption of hydroxypropyl methyl cellulose, and result of the test is shown in Table 4.
The binder dosage of table 4 investigates result table
It was found from the result of the test in table 4：The present invention use account for recipe quantity 10%-12% hydroxypropyl methyl celluloses as
Situation, tablet appearance, disintegration time limited and the dispersing uniformity effect of being pelletized during adhesive are preferable, therefore present invention selection accounts for recipe quantity
10%-12% hydroxypropyl methyl celluloses are used as adhesive.
3. it is swelled the selection of auxiliary material
Dispersible tablet is mainly medicine with least one disintegrant and being swelled supplementary product compatibility and forming.What is used at present is swelled auxiliary material
There are guar gum, XANTHAN GUM, alginates, glucan, amylum pregelatinisatum, HPMC, polysaccharide and calcium carboxymethylcellulose, hydroxypropyl fine
Tie up the hydrophilic high molecular polymers such as element.XANTHAN GUM, sodium alginate, glucan, HPMC and hydroxy propyl cellulose are compared in experiment
Element is swelled auxiliary material, using disintegration time as inspection target, the results are shown in Table 5.
Table 5 is swelled auxiliary material and investigates result table
It was found from the result of the test in table 5：Using glucan as when being swelled auxiliary material, the disintegration effect of dispersible tablet is best, therefore this
Invention selection glucan is to be swelled auxiliary material.Compare through experiment investigation, glucan is to account for prescription as being swelled auxiliary material to be best suitable for consumption
The 40% of amount.
4. the selection of surfactant
Surfactant has wetting and the effect of solubilising in pharmaceutical preparation, and surface is added in the prescription of dispersible tablet and is lived
Property agent is greatly improved the dissolution rate of dispersible tablet.Lauryl sodium sulfate, dodecyl sodium sulfate, Luo Bo are compared in experiment
Husky nurse and the dissolution experiment for not adding dispersible tablet in the case of three kinds of surfactant, the results are shown in Table 6.
The surfactant of table 6 investigates result table
Result of the test in table 6：In the dissolution results of three kinds of dispersible tablets, with lauryl sodium sulfate as
Result of extraction is best during surfactant, therefore present invention selection lauryl sodium sulfate is surfactant.Through experiment investigation pair
Than its consumption be recipe quantity 5% when tablet result of extraction it is best.
5. the selection of glidant
Powder flowbility is a critical nature in solid pharmaceutical preparation technique.Superfine silica gel powder, magnesium stearate are conventional
Glidant, can effectively improve the mobility of particle or powder in pelletizing press sheet or direct powder compression.Contrasted in experiment
2% superfine silica gel powder, 2% magnesium stearate, 2% magnesium stearate-superfine silica gel powder (1: 1) are as glidant, with disintegration time and hard
Spend for inspection target, progress overall merit.It the results are shown in Table 7.
The glidant of table 7 investigates result table
Result of the test in table 7：2% magnesium stearate-superfine silica gel powder (1: 1) is best as glidant effect, therefore
The present invention is from 2% magnesium stearate-superfine silica gel powder (1: 1) as glidant.
2nd, treatment progressive myatrophy, cerebral hemorrhage sequelae, the system of the pharmaceutical preparation prepared composition discrete piece of cardiac insufficiency
Preparation Method
Embodiment 1
It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation prepared composition discrete piece of cardiac insufficiency
Preparation method, comprises the following steps：
T1：Following components is weighed by weight：Trinosin 10000g, sodium alginate 20000g, hydroxypropyl first
Base cellulose 10000g, Gentran 40 000g, sodium carboxymethyl starch 5000g, lauryl sodium sulfate 5000g, superfine silica gel powder
1500g, magnesium stearate 1500g, cross 100 mesh sieves, standby；
T2：Prepare trinosin inclusion compound：Load weighted sodium alginate is taken to put in material-compound tank, the 60000g that adds water adds
Heat to heating at 45 DEG C makes to be swelled completely, and trinosin, insulated and stirred are slowly added under the conditions of maintaining the temperature at 45 DEG C
2h, puts to room temperature taking-up, in 50 DEG C of dry 12h of -0.06Mpa vacuums drying temperature, crushes, and crosses 80 mesh sieves, obtains triphosphoric acid
Adenosine disodium inclusion compound, it is 5.6% to determine its moisture；
T3：Take hydroxypropyl methyl cellulose to be dissolved in the ethanol of 40000g 65% and the dilute second of hydroxypropyl methyl cellulose is made
Alcoholic solution；
T4：It is another to take glucan, sodium carboxymethyl starch, lauryl sodium sulfate and the lower preparation gained Adenosine triphosphate of step T2
Glycosides disodium inclusion compound is added in mixer, is stirring evenly and then adding into hydroxypropyl methyl cellulose Diluted Alcohol solution, is stirred 10 minutes
Softwood is made；
T5：Take the softwood being made to put in oscillating granulator, cross 20 mesh sieve wet granulations, wet granular is put in drying box 60 DEG C and done
Dry 12h, takes out, and puts and 50 mesh sieves progress whole grain is crossed in pelletizing machine, obtain dry particl after whole grain, it is 5.7% to determine its moisture；
T6：Dry particl after grain is rounded to put in high efficient mixer, plus superfine silica gel powder and magnesium stearate, mix 30 minutes, be made
Treat tabletting trinosin mixed powder；
T7：Take trinosin mixed powder to put in tablet press machine, be pressed into plain piece, produce.
Embodiment 2
It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation prepared composition discrete piece of cardiac insufficiency
Preparation method, comprises the following steps：
T1：Following components is weighed by weight：Trinosin 10000g, sodium alginate 40000g, hydroxypropyl first
Base cellulose 20000g, Dextran 8 0000g, sodium carboxymethyl starch 20000g, lauryl sodium sulfate 10000g, superfine silica gel powder
3000g, magnesium stearate 3000g, cross 100 mesh sieves, standby；
T2：Prepare trinosin inclusion compound：Load weighted sodium alginate is taken to put in material-compound tank, the 80000g that adds water adds
Heat to heating at 65 DEG C makes to be swelled completely, and trinosin, insulated and stirred are slowly added under the conditions of maintaining the temperature at 65 DEG C
1h, puts to room temperature taking-up, in 65 DEG C of dry 8h of -0.09Mpa vacuums drying temperature, crushes, and crosses 80 mesh sieves, obtains Adenosine triphosphate
Glycosides disodium inclusion compound, it is 4.2% to determine its moisture；
T3：Take hydroxypropyl methyl cellulose to be dissolved in the ethanol of 80000g 65% and the dilute second of hydroxypropyl methyl cellulose is made
Alcoholic solution；
T4：It is another to take glucan, sodium carboxymethyl starch, lauryl sodium sulfate and the lower preparation gained Adenosine triphosphate of step T2
Glycosides disodium inclusion compound is added in mixer, is stirring evenly and then adding into hydroxypropyl methyl cellulose Diluted Alcohol solution, is stirred 15 minutes
Softwood is made；
T5：Take the softwood being made to put in oscillating granulator, cross 20 mesh sieve wet granulations, wet granular is put in drying box 80 DEG C and done
Dry 10h, takes out, and puts and 50 mesh sieves progress whole grain is crossed in pelletizing machine, obtain dry particl after whole grain, it is 4.1% to determine its moisture；
T6：Dry particl after grain is rounded to put in high efficient mixer, plus superfine silica gel powder and magnesium stearate, mix 30 minutes, be made
Treat tabletting trinosin mixed powder；
T7：Take trinosin mixed powder to put in tablet press machine, be pressed into plain piece, produce.
Embodiment 3
It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation prepared composition discrete piece of cardiac insufficiency
Preparation method, comprises the following steps：
T1：Following components is weighed by weight：Trinosin 10000g, sodium alginate 30000g, hydroxypropyl first
Base cellulose 15000g, Dextran 60 000g, sodium carboxymethyl starch 10000g, lauryl sodium sulfate 7500g, superfine silica gel powder
2000g, magnesium stearate 2000g, cross 100 mesh sieves, standby；
T2：Prepare trinosin inclusion compound：Load weighted sodium alginate is taken to put in material-compound tank, the 70000g that adds water adds
Heat to heating at 55 DEG C makes to be swelled completely, and trinosin, insulated and stirred are slowly added under the conditions of maintaining the temperature at 55 DEG C
1.5h, puts to room temperature taking-up, in 60 DEG C of dry 10h of -0.07Mpa vacuums drying temperature, crushes, and crosses 80 mesh sieves, obtains three phosphorus
Adenosine monophosphate disodium inclusion compound, it is 3.3% to determine its moisture；
T3：Take hydroxypropyl methyl cellulose to be dissolved in the ethanol of 60000g 65% and the dilute second of hydroxypropyl methyl cellulose is made
Alcoholic solution；
T4：It is another to take glucan, sodium carboxymethyl starch, lauryl sodium sulfate and the lower preparation gained Adenosine triphosphate of step T2
Glycosides disodium inclusion compound is added in mixer, is stirring evenly and then adding into hydroxypropyl methyl cellulose Diluted Alcohol solution, is stirred 12 minutes
Softwood is made；
T5：Take the softwood being made to put in oscillating granulator, cross 20 mesh sieve wet granulations, wet granular is put in drying box 70 DEG C and done
Dry 11h, takes out, and puts and 50 mesh sieves progress whole grain is crossed in pelletizing machine, obtain dry particl after whole grain, it is 3.2% to determine its moisture；
T6：Dry particl after grain is rounded to put in high efficient mixer, plus superfine silica gel powder and magnesium stearate, mix 30 minutes, be made
Treat tabletting trinosin mixed powder；
T7：Take trinosin mixed powder to put in tablet press machine, be pressed into plain piece, produce.
3rd, treatment progressive myatrophy, cerebral hemorrhage sequelae, the quality evaluation of the pharmaceutical preparation of cardiac insufficiency
1. determine disintegration time limited
Using Chinese Pharmacopoeia version " disintegration time limited inspection technique " (general rule 0921) in 2015, the above-mentioned embodiment 1- prepared is taken
3 samples and commercially available trinosin piece are detected, disintegration time limited is recorded respectively, 8 are the results are shown in Table.
The disintegration time mensuration situation of table 8
As can be seen from Table 8：Dispersible tablet prepared by pharmaceutical preparation of the present invention is than commercially available triphosphoric acid that common preparation method is made
Adenosine disodium piece time disintegration time limited shortens, and shows that it absorbs very fast, and energy quick acting is conducive to improving curative effect.
2. determine dissolution rate
Using Chinese Pharmacopoeia version " dissolution rate and drug release determination method " first method (general rule 0931) in 2015, above-mentioned preparation is taken
Good embodiment 1-3 samples and commercially available trinosin piece is detected that sample size is determined using using ultraviolet point
Light photometry, using trinosin as reference substance, absorbance is determined at 259nm, dissolution rate is then calculated, the results are shown in Table
9。
The dissolution determination situation of table 9
As can be seen from Table 9：Dispersible tablet prepared by pharmaceutical preparation of the present invention is than commercially available sugar coated tablet that common preparation method is made
Dissolution rate is significantly improved, and shows that its bioavilability is higher.
Claims (10)
1. a kind of treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency, it is characterised in that including
The component of following parts by weight：100 parts of trinosin, 200-400 parts of sodium alginate, hydroxypropyl methyl cellulose 100-
200 parts, 0-800 parts of Gentran 40,50-200 parts of sodium carboxymethyl starch, 50-100 parts of lauryl sodium sulfate, superfine silica gel powder 15-
30 parts, 15-30 parts of magnesium stearate.
2. progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency are treated as claimed in claim 1, its
It is characterised by, includes the component of following parts by weight：100 parts of trinosin, 300 parts of sodium alginate, hydroxypropyl methyl are fine
150 parts of dimension element, 0 part of Dextran 60,100 parts of sodium carboxymethyl starch, 75 parts of lauryl sodium sulfate, 20 parts of superfine silica gel powder, tristearin
Sour 20 parts of magnesium.
3. progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency are treated as claimed in claim 1 or 2,
Characterized in that, the pharmaceutical preparation prepared composition discrete piece.
4. a kind for the treatment of progressive myatrophy as claimed in claim 3, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency
The method of prepared composition discrete piece, comprises the following steps：
T1：Following components is weighed by weight：100 parts of trinosin, 200-400 parts of sodium alginate, hydroxypropyl methyl
100-200 parts of cellulose, 0-800 parts of Gentran 40,50-200 parts of sodium carboxymethyl starch, 50-100 parts of lauryl sodium sulfate,
15-30 parts of superfine silica gel powder, 15-30 parts of magnesium stearate, cross 100 mesh sieves, standby；
T2：Prepare trinosin inclusion compound；
T3：Take hydroxypropyl methyl cellulose to be dissolved in the ethanol of 400-800 parts 65% and hydroxypropyl methyl cellulose Diluted Alcohol is made
Solution；
T4：It is another to take glucan, sodium carboxymethyl starch, lauryl sodium sulfate and the lower preparation gained atriphos two of step T2
Sodium inclusion compound is added in mixer, is stirring evenly and then adding into hydroxypropyl methyl cellulose Diluted Alcohol solution, is stirred 10-15 minutes and is made
Into softwood；
T5：Take the softwood being made to put in oscillating granulator, cross 20 mesh sieve wet granulations, wet granular is put in drying box and dried, and takes out,
Put and 50 mesh sieves progress whole grain is crossed in pelletizing machine, obtain dry particl after whole grain；
T6：Dry particl after grain is rounded to put in high efficient mixer, plus superfine silica gel powder and magnesium stearate, mix 30 minutes, be made and wait to press
Piece trinosin mixed powder；
T7：Take trinosin mixed powder to put in tablet press machine, be pressed into plain piece, produce.
5. as claimed in claim 4 prepared by treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency
Into the preparation method of dispersible tablet, it is characterised in that the preparation method of trinosin inclusion compounds is under described step T2：
S1：Load weighted sodium alginate is taken to put in material-compound tank, adding water 600-800 parts to be heated to heating at 45-65 DEG C makes to be swelled
Entirely；
S2：Trinosin is slowly added under the conditions of maintaining the temperature at 45 DEG C -65 DEG C, insulated and stirred 1-2h is put to room temperature
After take out, be dried in vacuo 8-12h, crush, cross 80 mesh sieves, obtain trinosin inclusion compound.
6. as claimed in claim 5 prepared by treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency
Into the preparation method of dispersible tablet, it is characterised in that under described step S2 the vacuum drying vacuum be -0.06Mpa to -
0.09Mpa, drying temperature is 50 DEG C -65 DEG C, and drying time is 8h-12h.
7. as claimed in claim 5 prepared by treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency
Into the method for dispersible tablet, it is characterised in that the mixing speed is 40rpm-60rpm under described step S2.
8. as claimed in claim 5 prepared by treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency
Into the preparation method of dispersible tablet, it is characterised in that described step S2 lower gained trinosin inclusion compound control moisture
Content≤6%.
9. as claimed in claim 4 prepared by treatment progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency
Into the preparation method of dispersible tablet, it is characterised in that the drying temperature of the drying steps is 60 DEG C -80 DEG C under step T5, is done
The dry time is 10h-12h.
10. progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation system of cardiac insufficiency are treated as claimed in claim 4
The standby preparation method into dispersible tablet, it is characterised in that dry particl control moisture≤6% under step T5.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710306805.2A CN107233322A (en) | 2017-05-04 | 2017-05-04 | It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency |
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| CN201710306805.2A CN107233322A (en) | 2017-05-04 | 2017-05-04 | It is a kind of to treat progressive myatrophy, cerebral hemorrhage sequelae, the pharmaceutical preparation of cardiac insufficiency |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1666748A (en) * | 2004-03-10 | 2005-09-14 | 孙明杰 | Oral formulation of adetphos |
| CN103110602A (en) * | 2013-03-12 | 2013-05-22 | 成都天台山制药有限公司 | Disodium adenosine triphosphate troche medical composition |
-
2017
- 2017-05-04 CN CN201710306805.2A patent/CN107233322A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1666748A (en) * | 2004-03-10 | 2005-09-14 | 孙明杰 | Oral formulation of adetphos |
| CN103110602A (en) * | 2013-03-12 | 2013-05-22 | 成都天台山制药有限公司 | Disodium adenosine triphosphate troche medical composition |
Non-Patent Citations (3)
| Title |
|---|
| 刘克华: "三磷酸腺苷二钠片裂片问题的解决方法", 《中国生化药物杂志》 * |
| 国家药典委员会: "《中华人民共和国药典 2015年版 二部》", 30 June 2015, 中国医药科技出版社 * |
| 蒋伟杰: "ATP肠溶片薄膜包衣工艺", 《广东药学院学报》 * |
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