CN107260694A - One kind treats silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation - Google Patents
One kind treats silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation Download PDFInfo
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- CN107260694A CN107260694A CN201710449321.3A CN201710449321A CN107260694A CN 107260694 A CN107260694 A CN 107260694A CN 201710449321 A CN201710449321 A CN 201710449321A CN 107260694 A CN107260694 A CN 107260694A
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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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K9/2022—Organic macromolecular compounds
- 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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Abstract
Silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation are treated the invention discloses one kind.The preparation includes the component of following parts by weight：90 110 parts of hanfangchin A, 400 600 parts of beta cyclodextrin, 270 330 parts of hydroxypropyl methyl cellulose, 50 100 parts of polyvinylpyrrolidone, 300 500 parts of lactose, 150 250 parts of microcrystalline cellulose, 10 30 parts of lauryl sodium sulfate, 10 20 parts of magnesium stearate.Main ingredient composition hanfangchin A is prepared into inclusion compound by preparation method of the present invention using beta cyclodextrin inclusion technique, and main ingredient inclusion compound further then is prepared into sustained release tablets.Invention formulation has the advantages that to reduce medicining times, the steady effective blood concentration of maintenance, reduces toxic side effect, reduce medication accumulated dose, imitate and treat good, and its preparation method is simple, and production cost is low, consumes energy low, easily realizes industrialized production.
Description
Technical field
The invention belongs to field of medicine preparations, it is related to a kind of preparation, more particularly to one kind treats silicosis, rheumatalgia, pass
Section pain and neuralgic long-acting novel formulation.
Background technology
Hanfangchin A is menispermaceous plants Fourstamen Stephania Root Stephania tetrandra S.Moore dry root through carrying
Take, separate, after purification gained high-purity alkaloids chemicals.Modern pharmacological research shows that hanfangchin A has：
(1) antitumor action, can suppress growth of cancer cells, promote it dead, and mechanism of action may have with regulation BC1-2 and Bax expression
Close；(2) antibacterial action, can suppress the growth of methicillin-resistant staphylococcus aureus, and can influence and suppress Candida albicans
The link intermediate product such as glycolysis, energetic supersession generation, reach the synergistic effect of collaboration Fluconazole；(3) effectively slow down by
Cardiac muscle cell's hypertrophy trend caused by AB, can also reduce fibrosis and the inflammatory reaction of heart；(4) anti-arrhythmia, leads to
The reset for crossing influence Na+ reaches antiarrhythmic effect；(5) osteoporosis is suppressed, the sclerotin that can effectively suppress model mice is dredged
Pine；(6) pharmacological actions such as the diaphragmatocele of careless ether induction can effectively be reduced.Therefore, hanfangchin A is made into bulk drug, tablet and note
Penetrate liquid, wherein hanfangchin A piece is the chemical drugs preparation being made using hanfangchin A as raw material, hanfangchin A piece record in
State Food and Drug Administration's national drug standards, standard code is WS-10001 (HD-0700) -2002, and specification is
20mg/ pieces, for treating rheumatalgia, arthralgia, neuralgia, merge for lung cancer with low dose radiation；Also it is used for pure silicon
The phase of lung I, II, III and each phase quartz lung.But it is due to hanfangchin A poorly water-soluble, causes oral administration biaavailability low and curative effect
It is unstable.
In addition, there is toxicity result of study to show, hanfangchin A is in addition to above-mentioned therapeutic action, also with potential
Genetoxic and antimutagenic effect, because its pharmacological action is extensive, it is difficult to reach safely and effectively there is medication requirement and side effect is big.
Hanfangchin A piece is as general formulation, for treating during above-mentioned disease, 3 administrations of daily requirement, and every time after administration
There is drug concentration fluctuation larger, cause obvious " crest " and " trough " phenomenon, when blood concentration is in " crest ", can produce
Toxic side effect, or even can produce a toxic reaction to a drug, when blood concentration is in " trough ", then do not reach the Expected Results for the treatment of, it is unfavorable
In the treatment of disease.In addition, rheumatalgia, arthralgia, neuralgia, simple silicosis, quartz lung Disease need long-term treatment,
Injection is such as used for a long time to be inconvenient, medical treatment cost is high, the shortcoming of patient economy burden weight.
Sustained release and controlled-release administrating system (sustained-release and controlled-release drug
Delivery systems) it is novel Drug Delivery Systems with fastest developing speed in recent years.Atrigel (Sustained
Release Drug Delivery System SRDDS) refer to that medicine slowly discharges to non-constant velocity from preparation in vivo,
So as to extend pharmaceutically-active class drug delivery system, sustained release preparation can be described as to a specific kind, in pharmacy of Chinese materia medica
Sustained release preparation is defined as durative action preparation or sustained-release preparation.Compared with ordinary preparation, sustained release preparation has advantages below：1. reduce
Administration number of times, to half-life short or needs the medicine of frequent drug administration, can improve the compliance of patient；2. blood concentration is steady, subtracts
Few " peak valley " phenomenon, reduces toxic side effect, improves curative effect；3. the stability of drug therapy is increased.
The disclosure of background above technology contents is only used for inventive concept and the technical scheme that auxiliary understands the present invention, and it is not
The prior art of present patent application is necessarily belonged to, the applying date of the above in present patent application is being shown without tangible proof
In the case of disclosed, above-mentioned background technology should not be taken to evaluate the novelty and creativeness of the application.
The content of the invention
, there is medicine after administration every time dense in 3 administrations of daily requirement that the present invention exists for existing hanfangchin A piece
Degree fluctuation is larger, causes obvious " crest " and " trough " phenomenon, and easily generation toxic side effect or therapeutic effect are undesirable etc.
Problem has reduction medicining times there is provided one kind, maintains steady effective blood concentration, reduction toxic side effect, reduction medication total
Treatment silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation of the advantages of dosage, effect have been treated and preparation method thereof.
Technical scheme is as follows：
One kind treats silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, includes the component of following parts by weight：
90-110 parts of hanfangchin A, 400-600 parts of beta-schardinger dextrin, 270-330 parts of hydroxypropyl methyl cellulose, polyvinylpyrrolidine
50-100 parts of ketone, 300-500 parts of lactose, 150-250 parts of microcrystalline cellulose, 10-30 parts of lauryl sodium sulfate, magnesium stearate
10-20 parts.
Treatment silicosis described above, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, are most preferably preferably included following heavy
Measure the component of part：100 parts of hanfangchin A, 500 parts of beta-schardinger dextrin, 300 parts of hydroxypropyl methyl cellulose, polyvinylpyrrolidine
75 parts of ketone, 400 parts of lactose, 200 parts of microcrystalline cellulose, 20 parts of lauryl sodium sulfate, 15 parts of magnesium stearate.
More than one described preparation methods for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, including
Following steps：
S1：Component is weighed by following parts by weight：90-110 parts of hanfangchin A, 400-600 parts of beta-schardinger dextrin, hydroxypropyl
270-330 parts of methylcellulose, 50-100 parts of polyvinylpyrrolidone, 300-500 parts of lactose, microcrystalline cellulose 150-250
Part, 10-30 parts of lauryl sodium sulfate, 10-20 parts of magnesium stearate；
S2：Prepare hanfangchin A inclusion compound；
S3：Take polyvinylpyrrolidone plus Diluted Alcohol solution to make dissolving, 5% polyvinylpyrrolidone Diluted Alcohol is made molten
Liquid；
S4：Take hanfangchin A inclusion compound made from step S2 and hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose,
Lauryl sodium sulfate be pre-mixed 20-40min, plus step S3 5% polyvinylpyrrolidone Diluted Alcohol solution, stir 10-
15min, is made softwood, crosses the granulation of 16 sieve meshes, dries, dry particl is made；
S5：Dry particl made from taking step S4 crosses 20 mesh sieve whole grains, and stiffened fatty acid magnesium mixing 20-30min, tabletting is produced
The treatment silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation.
The preparation method of hanfangchin A inclusion compounds is under step S2 described above：
T1：Hanfangchin A plus 300-500 parts of absolute ethyl alcohols are taken to make to be dissolved into hanfangchin A ethanol solution；
T2：Beta-schardinger dextrin is placed in material-compound tank, 400-600 parts of water are added, heating dissolves it at 35-45 DEG C, obtains
Beta-schardinger dextrin solution；
T3：Hanfangchin A ethanol solution is slowly added into beta-schardinger dextrin solution, stirring while adding, temperature is kept
3-4h is stirred at 35-45 DEG C, puts and places 6-8h to rearmounted 4-6 DEG C of room temperature, filters, discards mother liquor, filter residue and drying takes
Go out, cross 80 mesh sieves, obtain hanfangchin A inclusion compound.
Further, mixing speed described in step T3 is 100-200rpm, and filter residue and drying temperature is 50-60 DEG C, when drying
Between be 8-12h, moisture≤5% of gained hanfangchin A inclusion compound.
Drying temperature described in step S4 described above is 80-100 DEG C, and drying time is 8-10h, obtained dry particl
Moisture≤5%.
Application of the long-acting novel formulation described above in treatment silicosis, rheumatalgia, arthralgia and neuralgia.
The beneficial effects of the invention are as follows：
1st, hanfangchin A sustained release tablets are made in hanfangchin A by the present invention, are steadily had with medicining times, maintenance are reduced
The advantages of blood concentration, reduction toxic side effect, reduction medication accumulated dose, the effect of effect have been treated, overcomes existing hanfangchin A piece
The administration of daily requirement 3 times of presence, it is larger to there is drug concentration fluctuation after administration every time, causes obvious " crest " and " trough "
Phenomenon, the problems such as easily producing toxic side effect or undesirable therapeutic effect.
2nd, the present invention is with beta-schardinger dextrin, hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose, lauryl sodium sulfate, poly-
Vinylpyrrolidone, magnesium stearate etc., 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.
3rd, formulation preparation method technique of the invention is simple, production equipment is operated without particular/special requirement, easily, consume energy it is low,
Time saving, production cost is low, easily realizes industrialized production.
Brief description of the drawings
Fig. 1 is medicine releasing curve diagram in sustained release tablets and commercially available sugar coated tablet.
As shown in figure 1, commercially available hanfangchin A piece (sugar coated tablet) 2 hourly average Accumulation dissolutions be reach 80% with
On, and the long-acting novel formulation obtained by the present invention just reached more than 80% in 10 hours its average accumulated releases, showed that it has
There is preferable slow release effect.
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
1st, influence of hydroxypropyl methyl cellulose (HPMC) specification to insoluble drug release
Present invention experiment has been respectively compared the high viscosity hydroxypropyl methyl celluloses of three kinds of different sizes, i.e. HPMCK4M,
When HPMCK15M, HPMCK100M are as slow-release material, the influence to hanfangchin A release the results are shown in Table 1.
Influence of the table 1HPMC different sizes to release
The result of table 1 shows, the HPMC of different size has a certain impact to the release of hanfangchin A, and viscosity is higher
Rate of releasing drug is lower, and relatively, the present invention selects K4M and K15M equivalent to the HPMC of two kinds of specifications of K4M and K15M release
Slow-release material is used as after mixing.
2nd, influence of hydroxypropyl methyl cellulose (HPMC) consumption to insoluble drug release
The ratio of Experimental Comparison of the present invention HPMC (after K4M and K15M mixed in equal amounts) and hanfangchin A bulk drug is 2:
1、3:1、4:To the influence of hanfangchin A release when 1,2 are the results are shown in Table.
Influence of the table 2HPMC ratios different from main ingredient to release
As shown in Table 2：Influences of the HPMC with hanfangchin A bulk drug ratio to hanfangchin A release is larger, HPMC
Ratio with hanfangchin A bulk drug is 3:When 1, drug release rate effect is best, therefore present invention selection HPMC and Stephania tetrandra first
The ratio of plain bulk drug is 3:1.
3rd, the selection of filler
The present invention, as filler, compared for the ratio of lactose and microcrystalline cellulose from lactose, microcrystalline cellulose in experiment
Example is 1:1,2:1,3:To the influence of drug release rate when 1,3 are the results are shown in Table.
The lactose of table 3 and influence of the microcrystalline cellulose different proportion to release
As shown in Table 3, when the lactose of different proportion and microcrystalline cellulose are as filler, to the release of hanfangchin A
Have an impact, sustained-release tablets release speed slows down with the increase of lactose and microcrystalline cellulose ratio, lactose and microcrystalline cellulose ratio
Example is 2:1 is preferable as drug release rate during filler, therefore present invention selection lactose and microcrystalline cellulose ratio are 2:1 conduct is filled out
Fill agent.
4th, the selection of adhesive
Experiment investigation of the present invention 10% starch slurry, 75% ethanol, 5% polyvinylpyrrolidone Diluted Alcohol solution are as viscous
To the influence of drug release rate during mixture, 4 are the results are shown in Table.
Influence result table of the adhesive of table 4 to release
As shown in Table 4, the present invention use the Diluted Alcohol solution of 5% polyvinylpyrrolidone as release during adhesive most
It is good, therefore the Diluted Alcohol solution of the present invention 5% polyvinylpyrrolidone of selection is used as adhesive.
5th, the investigation of magnesium stearate consumption
The release of sustained release tablets, is as a result shown in when the addition for having investigated magnesium stearate respectively is 1%, 2%, the 3% of piece weight
Table 5.
Influence result table of the consumption of the magnesium stearate of table 5 to release
As shown in Table 5, the release of medicine is preferable when the amount that magnesium stearate accounts for piece weight is 1%, therefore present invention selection is stearic
Sour magnesium accounts for the 1% of the amount of piece weight.
6th, the investigation of lauryl sodium sulfate consumption (interior addition)
Hanfangchin A has stronger hydrophobicity, therefore selection lauryl sodium sulfate can be played as surfactant
Wetting action.The addition of experiment investigation of the present invention lauryl sodium sulfate consumption (interior addition) for piece weight 1%, 2%,
The release of sustained release tablets, the results are shown in Table 6 when 3%.
Influence result table of the consumption of the lauryl sodium sulfate consumption of table 6 (interior addition) to release
As shown in Table 6, when the consumption of lauryl sodium sulfate consumption (interior addition) accounts for 1%, the 2% of the amount of piece weight, medicine
Release almost, preferably, thus the present invention selection lauryl sodium sulfate consumption (interior addition) consumption account for piece weight amount
1%-2%.
2nd, the preparation method for the treatment of silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Embodiment 1
A kind of preparation method for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, including following step
Suddenly：
S1：Component is weighed by following weight：Hanfangchin A 90g, beta-schardinger dextrin 400g, hydroxypropyl methyl cellulose
270g, polyvinylpyrrolidone 50g, lactose 300g, microcrystalline cellulose 150g, lauryl sodium sulfate 10g, magnesium stearate 10g；
S2：Prepare hanfangchin A inclusion compound：Hanfangchin A plus 300g absolute ethyl alcohols is taken to make to be dissolved into hanfangchin A
Ethanol solution；Beta-schardinger dextrin is placed in material-compound tank, 400g water is added, heating dissolves it at 35 DEG C, β-ring paste is obtained
Smart solution；Hanfangchin A ethanol solution is slowly added into beta-schardinger dextrin solution, stirring while adding, temperature is maintained at 35
DEG C 4h is stirred with 100rpm speed, put and place 6h to rearmounted 4 DEG C of room temperature, filter, discard mother liquor, 50 DEG C of filter residue is done
Dry 12h, takes out, and crosses 80 mesh sieves, obtains hanfangchin A inclusion compound, and detection moisture is 2.3%；
S3：Take polyvinylpyrrolidone plus Diluted Alcohol solution to make dissolving, 5% polyvinylpyrrolidone Diluted Alcohol is made molten
Liquid；
S4：Take hanfangchin A inclusion compound made from step S2 and hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose,
Lauryl sodium sulfate be pre-mixed 20min, plus step S3 5% polyvinylpyrrolidone Diluted Alcohol solution, stir 10min, system
Into softwood, the granulation of 16 sieve meshes is crossed, dry particl is made in 80 DEG C of dry 10h, and detection moisture is 2.1%；
S5：Dry particl made from taking step S4 crosses 20 mesh sieve whole grains, and stiffened fatty acid magnesium mixing 20min, tabletting is produced.
Embodiment 2
A kind of preparation method for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, including following step
Suddenly：
S1：Component is weighed by following weight：Hanfangchin A 110g, beta-schardinger dextrin 600g, hydroxypropyl methyl cellulose
330g, polyvinylpyrrolidone 100g, lactose 500g, microcrystalline cellulose 250g, lauryl sodium sulfate 30g, magnesium stearate
20g；
S2：Prepare hanfangchin A inclusion compound：Hanfangchin A plus 500g absolute ethyl alcohols is taken to make to be dissolved into hanfangchin A
Ethanol solution；Beta-schardinger dextrin is placed in material-compound tank, 600g water is added, heating dissolves it at 45 DEG C, β-ring paste is obtained
Smart solution；Hanfangchin A ethanol solution is slowly added into beta-schardinger dextrin solution, stirring while adding, temperature is maintained at 35
DEG C 3h is stirred with 200rpm speed, put and place 8h to rearmounted 6 DEG C of room temperature, filter, discard mother liquor, 60 DEG C of filter residue is done
Dry 8h, takes out, and crosses 80 mesh sieves, obtains hanfangchin A inclusion compound, and detection moisture is 2.2%；
S3：Take polyvinylpyrrolidone plus Diluted Alcohol solution to make dissolving, 5% polyvinylpyrrolidone Diluted Alcohol is made molten
Liquid；
S4：Take hanfangchin A inclusion compound made from step S2 and hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose,
Lauryl sodium sulfate be pre-mixed 40min, plus step S3 5% polyvinylpyrrolidone Diluted Alcohol solution, stir 15min, system
Into softwood, the granulation of 16 sieve meshes is crossed, dry particl is made in 100 DEG C of dry 8h, and detection moisture is 2.1%；
S5：Dry particl made from taking step S4 crosses 20 mesh sieve whole grains, and stiffened fatty acid magnesium mixing 30min, tabletting is produced.
Embodiment 3
A kind of preparation method for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, including following step
Suddenly：
S1：Component is weighed by following weight：Hanfangchin A 100g, beta-schardinger dextrin 500g, hydroxypropyl methyl cellulose
300g, polyvinylpyrrolidone 75g, lactose 400g, microcrystalline cellulose 200g, lauryl sodium sulfate 20g, magnesium stearate 10g；
S2：Prepare hanfangchin A inclusion compound：Hanfangchin A plus 400g absolute ethyl alcohols is taken to make to be dissolved into hanfangchin A
Ethanol solution；Beta-schardinger dextrin is placed in material-compound tank, 500g water is added, heating dissolves it at 40 DEG C, β-ring paste is obtained
Smart solution；Hanfangchin A ethanol solution is slowly added into beta-schardinger dextrin solution, stirring while adding, temperature is maintained at 40
DEG C 3.5h is stirred with 150rpm speed, put and place 7h to rearmounted 5 DEG C of room temperature, filter, discard mother liquor, 55 DEG C of filter residue is done
Dry 10h, takes out, and crosses 80 mesh sieves, obtains hanfangchin A inclusion compound, and detection moisture is 2.5%；
S3：Take polyvinylpyrrolidone plus Diluted Alcohol solution to make dissolving, 5% polyvinylpyrrolidone Diluted Alcohol is made molten
Liquid；
S4：Take hanfangchin A inclusion compound made from step S2 and hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose,
Lauryl sodium sulfate be pre-mixed 30min, plus step S3 5% polyvinylpyrrolidone Diluted Alcohol solution, stir 12min, system
Into softwood, the granulation of 16 sieve meshes is crossed, dry particl is made in 90 DEG C of dry 9h, and detection moisture is 2.4%；
S5：Dry particl made from taking step S4 crosses 20 mesh sieve whole grains, and stiffened fatty acid magnesium mixing 25min, tabletting is produced.
Embodiment 4
A kind of preparation method for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, including following step
Suddenly：
S1：Component is weighed by following weight：Hanfangchin A 95g, beta-schardinger dextrin 450g, hydroxypropyl methyl cellulose
285g, polyvinylpyrrolidone 60g, lactose 350g, microcrystalline cellulose 175g, lauryl sodium sulfate 15g, magnesium stearate 12g；
S2：Prepare hanfangchin A inclusion compound：Hanfangchin A plus 350g absolute ethyl alcohols is taken to make to be dissolved into hanfangchin A
Ethanol solution；Beta-schardinger dextrin is placed in material-compound tank, 450g water is added, heating dissolves it at 38 DEG C, β-ring paste is obtained
Smart solution；Hanfangchin A ethanol solution is slowly added into beta-schardinger dextrin solution, stirring while adding, temperature is maintained at 38
DEG C 4h is stirred with 130rpm speed, put and place 7h to rearmounted 5 DEG C of room temperature, filter, discard mother liquor, 52 DEG C of filter residue is done
Dry 11h, takes out, and crosses 80 mesh sieves, obtains hanfangchin A inclusion compound, and detection moisture is 2.7%；
S3：Take polyvinylpyrrolidone plus Diluted Alcohol solution to make dissolving, 5% polyvinylpyrrolidone Diluted Alcohol is made molten
Liquid；
S4：Take hanfangchin A inclusion compound made from step S2 and hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose,
Lauryl sodium sulfate be pre-mixed 25min, plus step S3 5% polyvinylpyrrolidone Diluted Alcohol solution, stir 11min, system
Into softwood, the granulation of 16 sieve meshes is crossed, dry particl is made in 85 DEG C of dry 10h, and detection moisture is 2.5%；
S5：Dry particl made from taking step S4 crosses 20 mesh sieve whole grains, and stiffened fatty acid magnesium mixing 22min, tabletting is produced.
Embodiment 5
A kind of preparation method for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, including following step
Suddenly：
S1：Component is weighed by following weight：Hanfangchin A 105g, beta-schardinger dextrin 550g, hydroxypropyl methyl cellulose
315g, polyvinylpyrrolidone 80g, lactose 450g, microcrystalline cellulose 225g, lauryl sodium sulfate 25g, magnesium stearate 17g；
S2：Prepare hanfangchin A inclusion compound：Hanfangchin A plus 450g absolute ethyl alcohols is taken to make to be dissolved into hanfangchin A
Ethanol solution；Beta-schardinger dextrin is placed in material-compound tank, 550g water is added, heating dissolves it at 42 DEG C, β-ring paste is obtained
Smart solution；Hanfangchin A ethanol solution is slowly added into beta-schardinger dextrin solution, stirring while adding, temperature is maintained at 42
DEG C 4h is stirred with 180rpm speed, put and place 7h to rearmounted 4 DEG C of room temperature, filter, discard mother liquor, 58 DEG C of filter residue is done
Dry 9h, takes out, and crosses 80 mesh sieves, obtains hanfangchin A inclusion compound, and detection moisture is 2.9%；
S3：Take polyvinylpyrrolidone plus Diluted Alcohol solution to make dissolving, 5% polyvinylpyrrolidone Diluted Alcohol is made molten
Liquid；
S4：Take hanfangchin A inclusion compound made from step S2 and hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose,
Lauryl sodium sulfate be pre-mixed 35min, plus step S3 5% polyvinylpyrrolidone Diluted Alcohol solution, stir 14min, system
Into softwood, the granulation of 16 sieve meshes is crossed, dry particl is made in 95 DEG C of dry 8h, and detection moisture is 2.8%；
S5：Dry particl made from taking step S4 crosses 20 mesh sieve whole grains, and stiffened fatty acid magnesium mixing 28min, tabletting is produced.
3rd, the quality evaluation for the treatment of silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
1st, dissolution in vitro
Using Chinese Pharmacopoeia version " dissolution rate and drug release determination method " first method (general rule 0931), Example 1- in 2015
5 samples prepared and commercially available hanfangchin A piece (sugar coated tablet) are detected that sample size determines and uses ultraviolet spectrometry
Photometry, using hanfangchin A as reference substance, absorbance is determined at 280nm, dissolution rate is then calculated, the results are shown in Table 7.
The dissolution determination situation of table 7
As can be seen from Table 7, long-acting novel formulation of the invention is than commercially available sugar coated tablet insoluble drug release phase that common preparation method is made
To steady, long half time, show that its bioavilability is high, while its adverse reaction is relatively small.
2nd, drug release patterns
Details are shown in Fig. 1.
The specific implementation of the invention is not to be limited to these illustrations for above content, is led for technology belonging to the present invention
For the those of ordinary skill in domain, without departing from the inventive concept of the premise, some simple deduction or replace can also be made,
The scope of patent protection that the present invention is determined by the claims submitted should be all considered as belonging to.
Claims (10)
1. one kind treats silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, it is characterised in that including following weight
The component of part：90-110 parts of hanfangchin A, 400-600 parts of beta-schardinger dextrin, 270-330 parts of hydroxypropyl methyl cellulose, poly- second
It is 50-100 parts of alkene pyrrolidone, 300-500 parts of lactose, 150-250 parts of microcrystalline cellulose, 10-30 parts of lauryl sodium sulfate, hard
10-20 parts of fatty acid magnesium.
2. treatment silicosis according to claim 1, rheumatalgia, arthralgia and neuralgic long-acting novel formulation, its feature exist
In including the component of following parts by weight：100 parts of hanfangchin A, 500 parts of beta-schardinger dextrin, 300 parts of hydroxypropyl methyl cellulose,
75 parts of polyvinylpyrrolidone, 400 parts of lactose, 200 parts of microcrystalline cellulose, 20 parts of lauryl sodium sulfate, 15 parts of magnesium stearate.
3. a kind for the treatment of silicosis according to claim 1 or 2, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Preparation method, it is characterised in that comprise the following steps：
S1：Component is weighed by following parts by weight：90-110 parts of hanfangchin A, 400-600 parts of beta-schardinger dextrin, hydroxypropyl methyl are fine
Tie up 270-330 parts of element, 50-100 parts of polyvinylpyrrolidone, 300-500 parts of lactose, 150-250 parts of microcrystalline cellulose, dodecane
10-30 parts of base sodium sulphate, 10-20 parts of magnesium stearate；
S2：Prepare hanfangchin A inclusion compound；
S3：Take polyvinylpyrrolidone plus Diluted Alcohol solution to make dissolving, 5% polyvinylpyrrolidone Diluted Alcohol solution is made；
S4：Take hanfangchin A inclusion compound made from step S2 and hydroxypropyl methyl cellulose, lactose, microcrystalline cellulose, 12
Sodium alkyl sulfate be pre-mixed 20-40min, plus step S3 5% polyvinylpyrrolidone Diluted Alcohol solution, stir 10-15min,
Softwood is made, crosses the granulation of 16 sieve meshes, dries, dry particl is made；
S5：Dry particl made from taking step S4 crosses 20 mesh sieve whole grains, and stiffened fatty acid magnesium mixing 20-30min, tabletting is produced described
Treat silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation.
4. the preparation side according to claim 3 for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Method, it is characterised in that the preparation method of hanfangchin A inclusion compound is described in step S2：
T1：Hanfangchin A plus 300-500 parts of absolute ethyl alcohols are taken to make to be dissolved into hanfangchin A ethanol solution；
T2：Beta-schardinger dextrin is placed in material-compound tank, 400-600 parts of water are added, heating dissolves it at 35-45 DEG C, obtains β-ring
Dextrin solution；
T3：Hanfangchin A ethanol solution is slowly added into beta-schardinger dextrin solution, stirring while adding, temperature is maintained at
35-45 DEG C of stirring 3-4h, puts and places 6-8h to rearmounted 4-6 DEG C of room temperature, filter, and discards mother liquor, and filter residue and drying is taken out,
80 mesh sieves are crossed, hanfangchin A inclusion compound is obtained.
5. the preparation side according to claim 4 for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Method, it is characterised in that mixing speed described in step T3 is 100-200rpm in the preparation method of hanfangchin A inclusion compound.
6. the preparation side according to claim 4 for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Method, it is characterised in that filter residue and drying temperature described in step T3 is 50-60 DEG C in the preparation method of hanfangchin A inclusion compound, is done
The dry time is 8-12h.
7. the preparation side according to claim 4 for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Method, it is characterised in that the moisture of hanfangchin A inclusion compound contains obtained by step T3 in the preparation method of hanfangchin A inclusion compound
Amount≤5%.
8. the preparation side according to claim 3 for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Method, it is characterised in that drying temperature described in step S4 is 80-100 DEG C, and drying time is 8-10h.
9. the preparation side according to claim 3 for treating silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation
Method, it is characterised in that moisture≤5% of the dry particl obtained by step S4.
10. treatment silicosis, rheumatalgia, arthralgia and neuralgic long-acting novel formulation according to claim any one of 1-2,
Characterized in that, application of the preparation in treatment silicosis, rheumatalgia, arthralgia and neuralgia.
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| CN1424112A (en) * | 2002-12-17 | 2003-06-18 | 上海医药工业研究院 | Water soluble dressing for insoluble medicines and preparation thereof |
| CN104955330A (en) * | 2012-09-13 | 2015-09-30 | Cba制药有限公司 | Tetrandrine pharmaceutical formulations and method |
| KR20140086210A (en) * | 2012-12-28 | 2014-07-08 | 한국식품연구원 | Composition comprising tetrandrine for treating obesity-induced inflammation |
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Application publication date: 20171020 |