CN102488660A - Sustained-release pellet containing pirfeudone - Google Patents
Sustained-release pellet containing pirfeudone Download PDFInfo
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- CN102488660A CN102488660A CN2011104310588A CN201110431058A CN102488660A CN 102488660 A CN102488660 A CN 102488660A CN 2011104310588 A CN2011104310588 A CN 2011104310588A CN 201110431058 A CN201110431058 A CN 201110431058A CN 102488660 A CN102488660 A CN 102488660A
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Abstract
The invention discloses a sustained-release pellet containing pirfeudone. The sustained-release pellet is prepared from 15-90 percent by mass of pirfeudone and the balance of pharmaceutically-acceptable auxiliary materials. Due to the adoption of the sustained-release pellet containing pirfeudone, the blood concentration can quickly reach treatment concentration, acting time can be kept for a long time, the blood concentration is stable, the phenomenon of 'peak valley' existing in ordinary preparation release is avoided, the sustained-release pellet has a more durable medicament effect, high bioavailability, low toxic and side effects and a more stable curative effect and is convenient to take, the taking times can be reduced from three times a day to one time or two times a day, the medicament taking compliance of a patient is enhanced, and the probability of abuse and outage is lowered.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of slow-release micro-pill that contains pirfenidone.
Background technology
Idiopathic pulmonary fibrosis (Idiopathie pulmonary fibrosis; IPF) being the most serious a kind of form of expression of interstitial lung disease (interstitiallung disease), is the disease that turns to main diseases Li Tezheng with diffusivity alveolar chronic inflammatory disease and interstitial fibers.The sickness rate of interstitial pulmonary fibrosis is in rising trend in recent years.Worldwide have 5,000,000 people to suffer from this disease at present nearly, such patient's average life is merely 2.8 years, and annual about 40000 patients are therefore and dead, and this disease also has obvious increase at China's sickness rate.
The known factor of pulmonary fibrosis that causes has at present: radiation and medicine; Occupational exposure; Inherited genetic factors, other factors also have sarcoidosis (Sarcoidosis), chronic obstructive pulmonary disease (COPD), pulmonary tuberculosis, fungal infection of lung, parasitic disease of lung asthma, SARS, the human world infection of influenza bird flu virus etc.Pulmonary fibrosis has potential huge pathogenesis basis, and many common basic diseases all might cause the fibrosis of pulmonary, should cause the greater attention of medical science pharmaceutical field.
At present 17-hydroxy-11-dehydrocorticosterone and immunosuppressant are mainly adopted in the treatment of IPF,, only have the part patient effective with to anti-inflammatory, but effect and unsatisfactory.Though diagnosis and the treatment guide (draft) of IPF have been formulated in April, 2002 China medical association respiratory disease credit meeting, still do not have a kind of gratifying Therapeutic Method so far.
Pirfenidone (pirfenidone; PFD); 5-methyl isophthalic acid-phenyl-2-(1H)-pyridone; Be at the synthetic micromolecular compound seventies, Recent study person finds that it has inhibitory action for the fibrosis of tissue, and increasing result of the test has confirmed the significant curative effect of pirfenidone aspect fibrosis.Pirfenidone can be through reducing pulmonary vascular permeability, downward modulation iuntercellular adhesion molecule ICAM-1 level, the inflammation-inhibiting cell migration and suppress transforming growth factor TGF-β and I type at transcriptional level, the III collagen mRNA is expressed its effect of bringing into play.The fibroblast that can suppress lung, the leiomyoma cell proliferation suppresses fibrosis and changes; Improve the injury of lung that bleomycin causes, suppress the pneumonia reaction, alleviate the pulmonary fibrosis degree; In addition, hepatic fibrosis, renal fibrosis, myocardial fibrosis etc. have all been shown good inhibition effect.Existing at present tablet goes on the market in Japan.
But common oral solid formulation peak reaching time of blood concentration of pirfenidone and half-life are shorter; Repeatedly take medicine; Make blood drug level be prone to produce " peak valley " phenomenon, drug effect can not be brought into play lastingly, and can strengthen the untoward reaction of medicine; Thereby make that the compliance of taking medicine for a long time is poor, influence the clinical effectiveness of medicine.
Summary of the invention
Technical problem to be solved by this invention is the deficiency to above-mentioned prior art, and a kind of slow-release micro-pill that contains pirfenidone is provided.This slow-release micro-pill can make blood drug level reach treatment concentration rapidly, can keep longer action time again, and blood drug level is steady; Avoid " peak valley " phenomenon of ordinary preparation release, drug effect is more lasting, and bioavailability is high; Taking convenience, toxic and side effects is low, and curative effect is more stable; And medicining times is reduced to once-a-day or twice by three times on the original one, strengthens patient's drug compliance, the probability that has reduced abuse and stopped using.
For solving the problems of the technologies described above, the technical scheme that the present invention adopts is: a kind of slow-release micro-pill that contains pirfenidone is characterized in that said slow-release micro-pill is the slow-release micro-pill of being processed by pirfenidone and pharmaceutically acceptable auxiliary material; The quality percentage composition of pirfenidone is 15%～90% in the said slow-release micro-pill, and surplus is auxiliary material.
Above-mentioned a kind of slow-release micro-pill that contains pirfenidone, said slow-release micro-pill comprises celphere, medicine layer, slow release layer and pastille release layer from inside to outside successively; The quality percentage composition of said slow-release micro-pill empty ball core is 30%～60%; Said medicine layer comprises 10%～50% the pirfenidone that accounts for whole slow-release micro-pill quality and 1%～10% the binding agent that accounts for whole slow-release micro-pill quality; Said slow release layer comprises 1%～5% the framework material that accounts for whole slow-release micro-pill quality, 0.5%～2.5% plasticizer that accounts for whole slow-release micro-pill quality and 1%～5% the antiplastering aid that accounts for whole slow-release micro-pill quality; Said pastille release layer comprises 5%～30% the pirfenidone that accounts for whole slow-release micro-pill quality and 1%～5% the binding agent that accounts for whole slow-release micro-pill quality.
Above-mentioned a kind of slow-release micro-pill that contains pirfenidone; Said binding agent is one or more in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is one or more in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is one or more in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol, and said antiplastering aid is one or more in Pulvis Talci, silicon dioxide and the magnesium stearate.
Above-mentioned a kind of slow-release micro-pill that contains pirfenidone, said slow-release micro-pill is by containing pill core and slow release ball core mixes; The said pill core that contains is made up of celphere and the medicine layer that is wrapped on the celphere; Wherein celphere accounts for 20%～40% of whole slow-release micro-pill quality, and said medicine layer comprises 10%～50% the pirfenidone that accounts for whole slow-release micro-pill quality and 1%～30% the binding agent that accounts for whole slow-release micro-pill quality; Said slow release ball core is made up of celphere and the pastille slow-release layer that is wrapped on the celphere; Wherein celphere accounts for 10%～20% of whole slow-release micro-pill quality, said pastille slow-release layer comprises 5%～30% the pirfenidone that accounts for whole slow-release micro-pill quality, account for whole slow-release micro-pill quality 1%～5% framework material, account for 0.5%～2.5% plasticizer of whole slow-release micro-pill quality and account for 1%～5% antiplastering aid of whole slow-release micro-pill quality.
Above-mentioned a kind of slow-release micro-pill that contains pirfenidone; Said binding agent is one or more in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is one or more in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is one or more in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol, and said antiplastering aid is one or more in Pulvis Talci, silicon dioxide and the magnesium stearate.
Above-mentioned a kind of slow-release micro-pill that contains pirfenidone, said slow-release micro-pill is mixed by rapid release ball core and slow release ball core; Said rapid release ball core comprises 15%～30% the pirfenidone that accounts for whole slow-release micro-pill quality, account for 1%～5% porogen of whole slow-release micro-pill quality and account for 1%～10% binding agent of whole slow-release micro-pill quality; Said slow release ball core is formed by containing pill core and being wrapped in the slow release layer that contains on the pill core; The said pill core that contains comprises 30%～60% the pirfenidone that accounts for whole slow-release micro-pill quality, accounts for 2%～10% porogen of whole slow-release micro-pill quality and accounts for 2%～20% binding agent of whole slow-release micro-pill quality, and said slow release layer comprises 1%～5% the framework material that accounts for whole slow-release micro-pill quality, account for 1%～5% porogen of whole slow-release micro-pill quality and account for 1%～5% antiplastering aid of whole slow-release micro-pill quality.
Above-mentioned a kind of slow-release micro-pill that contains pirfenidone; Said binding agent is one or more in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is one or more in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said porogen is one or more in Polyethylene Glycol, microcrystalline Cellulose and the lactose, and said antiplastering aid is one or more in Pulvis Talci, silicon dioxide and the magnesium stearate.
First kind of method for preparing that contains the slow-release micro-pill of pirfenidone of the present invention may further comprise the steps:
Step 1, preparation contain pill core: take by weighing celphere; And take by weighing pirfenidone and binding agent according to the percentage composition of each component of medicine layer; The binding agent that takes by weighing is dissolved in ethanol or the purified water, is mixed with the binding agent mass concentration and is 0.4%～15% solution; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release layer: the percentage composition according to each component of slow release layer takes by weighing framework material, plasticizer and antiplastering aid; Framework material is dissolved in ethanol or the purified water; Be mixed with the framework material mass concentration and be 1%～10% solution; Add plasticizer and antiplastering aid then, stirring obtains the suspendible coating solution; At last the pill core that contains for preparing in the step 1 is placed airpillow-dry granulator, in granulator, spray into the suspendible coating solution and carry out coating, obtain the pill core that contains of slow release layer parcel after the drying;
Step 3, preparation pastille release layer: the percentage composition according to each component of pastille release layer takes by weighing pirfenidone and binding agent, and binding agent is dissolved in ethanol or the purified water, is mixed with the binding agent mass concentration and is 1%～12% solution; Then pirfenidone is added in the solution, stirring obtains suspension; The pill core that contains with the slow release layer parcel for preparing in the step 2 places airpillow-dry granulator at last, in granulator, sprays into suspension and carries out coating, obtains containing the slow-release micro-pill of pirfenidone after the drying.
The method for preparing that another kind of the present invention contains the slow-release micro-pill of pirfenidone may further comprise the steps:
Step 1, preparation contain pill core: the percentage composition according to containing pill core branch component takes by weighing celphere, pirfenidone and binding agent, and binding agent is dissolved in ethanol or the purified water, is mixed with the binding agent mass concentration and is 0.4%～15% solution; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release ball core: the percentage composition according to each component of slow release ball core takes by weighing celphere, pirfenidone, framework material, plasticizer and antiplastering aid; Framework material is dissolved in ethanol or the purified water; Be mixed with the framework material mass concentration and be 1%～10% solution; Add pirfenidone, plasticizer and antiplastering aid then, stirring obtains slow-release suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into slow-release suspension and carry out coating, obtain slow release ball core after the drying;
Step 3, preparation slow-release micro-pill: the slow release ball core for preparing in pill core and the step 2 that contains for preparing in the step 1 is mixed in proportion, obtain containing the slow-release micro-pill of pirfenidone.
The method for preparing that the third contains the slow-release micro-pill of pirfenidone of the present invention may further comprise the steps:
Step 1, preparation contain pill core: take by weighing pirfenidone, binding agent and porogen according to the percentage composition that contains each component of pill core; Pirfenidone, binding agent and porogen mix homogeneously are obtained mixed powder; In the coating pan with the mixed powder input rotation of 2/7ths amounts; According to spraying purified water and the process cycling of adding the residue mixed powder, with the round as a ball glomeration granule of mixed powder; Then spherical particle is crossed 30 mesh sieves, the oversize after sieving is crossed 25 mesh sieves,, remove siftage and obtain containing pill core crossing siftage oven dry back behind 25 mesh sieves after 30 mesh sieves;
Step 2, preparation slow release ball core: the percentage composition according to each component of slow release layer takes by weighing framework material, porogen and antiplastering aid; Framework material is dissolved in ethanol or the purified water; Be mixed with the framework material mass concentration and be 1%～10% solution; Add porogen and antiplastering aid then, stirring obtains the suspendible coating solution; The part that at last step 1 is prepared contains pill core and places airpillow-dry granulator, in granulator, sprays into the suspendible coating solution and carries out coating, obtains slow release ball core after the drying;
Step 3, preparation slow-release micro-pill: the residue for preparing in the step 1 is contained pill core as the slow release ball core mix homogeneously for preparing in rapid release ball core and the step 2, obtain containing the slow-release micro-pill of pirfenidone.
Slow-release micro-pill of the present invention can be made into granule or capsule.
The method for preparing of granule is: the slow-release micro-pill that will contain pirfenidone is packed in the aluminium foil bag, obtains containing the slow-releasing granules of pirfenidone, and wherein every bag contains pirfenidone 0.2g～0.8g; The consumption of slow-releasing granules is every day 1～2 time, each 1～2 bag.
The method for preparing of capsule is: the slow-release micro-pill that will contain pirfenidone is packed in the capsule, obtains containing the slow releasing capsule of pirfenidone, and wherein every capsules contains pirfenidone 0.2g～0.4g; The consumption of slow releasing capsule is every day 1～2 time, each 1～2.
The present invention compared with prior art has the following advantages:
1, the slow-release micro-pill distribution table area in gastrointestinal tract that contains pirfenidone of the present invention increases, and local excitation reduces or eliminates to gastrointestinal tract, and bioavailability increases; In addition; The micropill particle diameter is little, and it is little to receive digestive tract food to carry the rhythm and pace of moving things to influence, and not influenced by gastric emptying.
2, the slow-release micro-pill that contains pirfenidone of the present invention can make blood drug level reach treatment concentration rapidly, can keep longer action time again, and blood drug level is steady; Avoid " peak valley " phenomenon of ordinary preparation release, drug effect is more lasting, and bioavailability is high; Taking convenience, toxic and side effects is low, and curative effect is more stable; And medicining times is reduced to once-a-day or twice by three times on the original one, strengthens patient's drug compliance, the probability that has reduced abuse and stopped using.
The drug release behavior of the pharmaceutical preparation of 3, being processed by the slow-release micro-pill that contains pirfenidone of the present invention is a summation of forming several micropill drug release behaviors of a dosage; The error of indivedual micropills in preparation and defective are unlikely drug release behavior to whole preparation and produce and have a strong impact on, so repeatability and concordance in release accumulation behavior obviously are superior to tablet.
4, capsule or the granule processed by the slow-release micro-pill that contains pirfenidone of the present invention can increase stability of drug, cover disagreeable taste, good looking appearance, and good fluidity, dust is little, is convenient to control of quality during production, improves production environment.
5, the micropill packing on demand of the different rate of releasing drug of the present invention both can make medicine reach therapeutic effect rapidly, can keep long action time again; Blood drug level is steady, can effectively reduce medicining times, and repeatability is good; Untoward reaction is low, can improve patient's drug compliance.
The specific embodiment
Embodiment 1
The slow-release micro-pill of present embodiment comprises celphere, medicine layer, slow release layer and pastille release layer from inside to outside successively; The quality percentage composition of said slow-release micro-pill empty ball core is 30%; Said medicine layer comprises 50% the pirfenidone that accounts for whole slow-release micro-pill quality and 3% the binding agent (30 POVIDONE K 30 BP/USP 30) that accounts for whole slow-release micro-pill quality; Said slow release layer comprises 2% the framework material (ethyl cellulose) that accounts for whole slow-release micro-pill quality, accounts for 2.5% plasticizer (triethyl citrate) of whole slow-release micro-pill quality and accounts for 1.5% antiplastering aid (Pulvis Talci) of whole slow-release micro-pill quality; Said pastille release layer comprises 10% the pirfenidone that accounts for whole slow-release micro-pill quality and 1% the binding agent (30 POVIDONE K 30 BP/USP 30) that accounts for whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing the 300g celphere, 500g pirfenidone and 30g binding agent 30 POVIDONE K 30 BP/USP 30 are dissolved in binding agent in the ethanol, are mixed with the binding agent mass concentration and are 0.4% solution; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release layer: take by weighing 20g framework material ethyl cellulose; 25g plasticizer triethyl citrate and 15g antiplastering aid Pulvis Talci; Framework material is dissolved in the ethanol; Be mixed with the framework material mass concentration and be 5% solution, add plasticizer and antiplastering aid then, stirring obtains the suspendible coating solution; At last the pill core that contains for preparing in the step 1 is placed airpillow-dry granulator, in granulator, spray into the suspendible coating solution and carry out coating, obtain the pill core that contains of slow release layer parcel after the drying;
Step 3, preparation pastille release layer: take by weighing 100g pirfenidone and 10g binding agent 30 POVIDONE K 30 BP/USP 30, binding agent is dissolved in the ethanol, be mixed with the binding agent mass concentration and be 1% solution; Then pirfenidone is added in the solution, stirring obtains suspension; The pill core that contains with the slow release layer parcel for preparing in the step 2 places airpillow-dry granulator at last, in granulator, sprays into suspension and carries out coating, obtains containing the slow-release micro-pill of pirfenidone after the drying.
Embodiment 2
Present embodiment is identical with embodiment 1, and wherein difference is: said binding agent is sodium carboxymethyl cellulose, sucrose or starch, perhaps is at least two kinds in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin or polyvinyl alcohol, perhaps is at least two kinds in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is Polyethylene Glycol, phthalic acid ester or spermol; Perhaps be at least two kinds in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol; Said antiplastering aid is silicon dioxide or magnesium stearate, perhaps is at least two kinds in Pulvis Talci, silicon dioxide and the magnesium stearate.
Embodiment 3
The slow-release micro-pill of present embodiment comprises celphere, medicine layer, slow release layer and pastille release layer from inside to outside successively; The quality percentage composition of said slow-release micro-pill empty ball core is 60%; Said medicine layer comprises 10% the pirfenidone that accounts for whole slow-release micro-pill quality and 10% the binding agent (1.5% sodium carboxymethyl cellulose and 8.5% sucrose) that accounts for whole slow-release micro-pill quality; Said slow release layer comprises 5% the framework material (2% cellulose acetate and 3% hypromellose) that accounts for whole slow-release micro-pill quality, accounts for 0.5% plasticizer (spermol) of whole slow-release micro-pill quality and accounts for 5% antiplastering aid (4.5% silicon dioxide and 0.5% magnesium stearate) of whole slow-release micro-pill quality; Said pastille release layer comprises 5% the pirfenidone that accounts for whole slow-release micro-pill quality and 4.5% the binding agent (1.0% sodium carboxymethyl cellulose and 3.5% sucrose) that accounts for whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing the 600g celphere, and the 100g pirfenidone, 15g sodium carboxymethyl cellulose and 85g sucrose in purified water, are mixed with the binding agent mass concentration and are 15% solution with binding agent sodium carboxymethyl cellulose and sucrose dissolved; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release layer: take by weighing the 20g cellulose acetate, 30g hypromellose, 5g spermol; 45g silicon dioxide and 5g magnesium stearate; Framework material cellulose acetate and hypromellose are dissolved in the ethanol, are mixed with the framework material mass concentration and are 1% solution, add the plasticizer spermol then; Antiplastering aid silicon dioxide and magnesium stearate, stirring obtains the suspendible coating solution; At last the pill core that contains for preparing in the step 1 is placed airpillow-dry granulator, in granulator, spray into the suspendible coating solution and carry out coating, obtain the pill core that contains of slow release layer parcel after the drying;
Step 3, preparation pastille release layer: take by weighing the 50g pirfenidone, 10g sodium carboxymethyl cellulose and 35g sucrose in purified water, are mixed with the binding agent mass concentration and are 12% solution with binding agent sodium carboxymethyl cellulose and sucrose dissolved; Then pirfenidone is added in the solution, stirring obtains suspension; The pill core that contains with the slow release layer parcel for preparing in the step 2 places airpillow-dry granulator at last, in granulator, sprays into suspension and carries out coating, obtains containing the slow-release micro-pill of pirfenidone after the drying.
Embodiment 4
Present embodiment is identical with embodiment 3; Wherein difference is: said binding agent is a kind of in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch or more than three kinds; Perhaps being sodium carboxymethyl cellulose and 30 POVIDONE K 30 BP/USP 30, perhaps is Carboxymethyl cellulose sodium and starch, perhaps is 30 POVIDONE K 30 BP/USP 30 and sucrose; Perhaps being 30 POVIDONE K 30 BP/USP 30 and starch, perhaps is sucrose and starch; Said framework material is a kind of in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol or more than three kinds; Perhaps being two kinds in ethyl cellulose, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol, perhaps is the mixture of a kind of and cellulose acetate in ethyl cellulose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is triethyl citrate, Polyethylene Glycol or phthalic acid ester, perhaps is at least two kinds in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol; Said antiplastering aid is Pulvis Talci, silicon dioxide or magnesium stearate, perhaps is Pulvis Talci and silicon dioxide, perhaps is Pulvis Talci and magnesium stearate.
Embodiment 5
The slow-release micro-pill of present embodiment comprises celphere, medicine layer, slow release layer and pastille release layer from inside to outside successively; The quality percentage composition of said slow-release micro-pill empty ball core is 40%; Said medicine layer comprises 20% the pirfenidone that accounts for whole slow-release micro-pill quality and 1% the binding agent (starch) that accounts for whole slow-release micro-pill quality; Said slow release layer comprises 1% the framework material (polyvinyl alcohol) that accounts for whole slow-release micro-pill quality, accounts for 2% plasticizer (phthalic acid ester) of whole slow-release micro-pill quality and accounts for 1% antiplastering aid (silicon dioxide) of whole slow-release micro-pill quality; Said pastille release layer comprises 30% the pirfenidone that accounts for whole slow-release micro-pill quality and 5% the binding agent (starch) that accounts for whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing the 400g celphere, 200g pirfenidone and 10g starch add binder starch in the purified water, are mixed with the binding agent mass concentration and are 8% solution; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release layer: take by weighing the 10g polyvinyl alcohol; 20g phthalic acid ester and 10g silicon dioxide; The framework material polyvinyl alcohol is dissolved in the purified water; Be mixed with the framework material mass concentration and be 5% solution, add plasticizer phthalic acid ester and antiplastering aid silicon dioxide then, stirring obtains the suspendible coating solution; At last the pill core that contains for preparing in the step 1 is placed airpillow-dry granulator, in granulator, spray into the suspendible coating solution and carry out coating, obtain the pill core that contains of slow release layer parcel after the drying;
Step 3, preparation pastille release layer: take by weighing the 300g pirfenidone, 50g starch adds binder starch in the purified water, is mixed with the binding agent mass concentration and is 6% solution; Then pirfenidone is added in the solution, stirring obtains suspension; The pill core that contains with the slow release layer parcel for preparing in the step 2 places airpillow-dry granulator at last, in granulator, sprays into suspension and carries out coating, obtains containing the slow-release micro-pill of pirfenidone after the drying.
Embodiment 6
Present embodiment is identical with embodiment 5, and wherein difference is: said binding agent is sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30 or sucrose, perhaps is at least two kinds in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose or acroleic acid resin, perhaps is at least two kinds in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is triethyl citrate, Polyethylene Glycol or spermol, perhaps is at least two kinds in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol; Said antiplastering aid is Pulvis Talci or magnesium stearate, perhaps is at least two kinds in Pulvis Talci, silicon dioxide and the magnesium stearate.
Embodiment 7
The slow-release micro-pill of present embodiment is by containing pill core and slow release ball core mixes; The said pill core that contains is made up of celphere and the medicine layer that is wrapped on the celphere; Wherein celphere accounts for 40% of whole slow-release micro-pill quality, and said medicine layer comprises 10% the pirfenidone that accounts for whole slow-release micro-pill quality and 30% the binding agent that accounts for whole slow-release micro-pill quality (5% sodium carboxymethyl cellulose, 10% 30 POVIDONE K 30 BP/USP 30,5% sucrose and 10% starch); Said slow release ball core is made up of celphere and the pastille slow-release layer that is wrapped on the celphere; Wherein celphere accounts for 10% of whole slow-release micro-pill quality, said pastille slow-release layer comprises 5% the pirfenidone that accounts for whole slow-release micro-pill quality, account for whole slow-release micro-pill quality 3.5% framework material (2% methylcellulose and 1.5% acroleic acid resin), account for 0.5% plasticizer (triethyl citrate) of whole slow-release micro-pill quality and account for 1% antiplastering aid (Pulvis Talci) of whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing the 400g celphere, 100g pirfenidone, 50g sodium carboxymethyl cellulose; 100g 30 POVIDONE K 30 BP/USP 30; 50g sucrose and 100g starch, with the binding agent sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30; Sucrose and starch dissolution are mixed with the binding agent mass concentration and are 15% solution in purified water; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release ball core: take by weighing the 100g celphere, 50g pirfenidone, 20g methylcellulose; The 15g acroleic acid resin; 5g triethyl citrate and 10g Pulvis Talci are dissolved in framework material methylcellulose and acroleic acid resin in the purified water, are mixed with the framework material mass concentration and are 1%～10% solution; Add pirfenidone, plasticizer triethyl citrate and antiplastering aid Pulvis Talci then, stirring obtains slow-release suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into slow-release suspension and carry out coating, obtain slow release ball core after the drying;
Step 3, preparation slow-release micro-pill:, obtain containing the slow-release micro-pill of pirfenidone with the slow release ball core mix homogeneously for preparing in pill core and the step 2 that contains for preparing in the step 1.
Embodiment 8
Present embodiment is identical with embodiment 7, and wherein difference is: said binding agent be in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch a kind of, two or three; Said framework material is a kind of in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol or more than three kinds; Perhaps being two kinds in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, acroleic acid resin and the polyvinyl alcohol, perhaps is the mixture of a kind of and methylcellulose in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose and the polyvinyl alcohol; Said plasticizer is Polyethylene Glycol, phthalic acid ester or spermol, perhaps is at least two kinds in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol; Said antiplastering aid is silicon dioxide or magnesium stearate, perhaps is at least two kinds in Pulvis Talci, silicon dioxide and the magnesium stearate.
Embodiment 9
The slow-release micro-pill of present embodiment is by containing pill core and slow release ball core mixes; The said pill core that contains is made up of celphere and the medicine layer that is wrapped on the celphere; Wherein celphere accounts for 20% of whole slow-release micro-pill quality, and said medicine layer comprises 50% the pirfenidone that accounts for whole slow-release micro-pill quality and 1% the binding agent (sodium carboxymethyl cellulose) that accounts for whole slow-release micro-pill quality; Said slow release ball core is made up of celphere and the pastille slow-release layer that is wrapped on the celphere; Wherein celphere accounts for 15% of whole slow-release micro-pill quality, said pastille slow-release layer comprises 10% the pirfenidone that accounts for whole slow-release micro-pill quality, account for whole slow-release micro-pill quality 1% framework material (hydroxyethyl-cellulose), account for 1% plasticizer (phthalic acid ester) of whole slow-release micro-pill quality and account for 2% antiplastering aid (silicon dioxide) of whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing the 200g celphere, and the 500g pirfenidone, 10g binding agent sodium carboxymethyl cellulose is dissolved in binding agent in the purified water, is mixed with the binding agent mass concentration and is 0.4%～15% solution; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release ball core: take by weighing the 150g celphere; The 100g pirfenidone, 10g hydroxyethyl-cellulose, 10g phthalic acid ester and 20g silicon dioxide; The framework material hydroxyethyl-cellulose is dissolved in the ethanol; Be mixed with the framework material mass concentration and be 1% solution, add pirfenidone, plasticizer phthalic acid ester and antiplastering aid silicon dioxide then, stirring obtains slow-release suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into slow-release suspension and carry out coating, obtain slow release ball core after the drying;
Step 3, preparation slow-release micro-pill:, obtain containing the slow-release micro-pill of pirfenidone with the slow release ball core mix homogeneously for preparing in pill core and the step 2 that contains for preparing in the step 1.
Embodiment 10
Present embodiment is identical with embodiment 9, and wherein difference is: said binding agent is 30 POVIDONE K 30 BP/USP 30, sucrose or starch, perhaps is at least two kinds in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is ethyl cellulose, cellulose acetate, hypromellose, hymetellose, methylcellulose, acroleic acid resin or polyvinyl alcohol, perhaps is at least two kinds in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is triethyl citrate, Polyethylene Glycol or spermol, perhaps is at least two kinds in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol; Said antiplastering aid is Pulvis Talci or magnesium stearate, perhaps is at least two kinds in Pulvis Talci, silicon dioxide and the magnesium stearate.
Embodiment 11
The slow-release micro-pill of present embodiment is by containing pill core and slow release ball core mixes; The said pill core that contains is made up of celphere and the medicine layer that is wrapped on the celphere; Wherein celphere accounts for 15% of whole slow-release micro-pill quality, and said medicine layer comprises 15% the pirfenidone that accounts for whole slow-release micro-pill quality and 7.5% the binding agent (4% sucrose and 3.5% starch) that accounts for whole slow-release micro-pill quality; Said slow release ball core is made up of celphere and the pastille slow-release layer that is wrapped on the celphere; Wherein celphere accounts for 20% of whole slow-release micro-pill quality, said pastille slow-release layer comprises 30% the pirfenidone that accounts for whole slow-release micro-pill quality, account for whole slow-release micro-pill quality 5% framework material (hymetellose), account for 2.5% plasticizer (1% triethyl citrate, 0.5% Polyethylene Glycol, 0.5% phthalic acid ester and 0.5% spermol) of whole slow-release micro-pill quality and account for 5% antiplastering aid (2% Pulvis Talci, 1% silicon dioxide and 2% magnesium stearate) of whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing the 150g celphere, and the 150g pirfenidone, 40g sucrose and 35g starch in purified water, are mixed with the binding agent mass concentration and are 0.4%～15% solution with binding agent sucrose and starch dissolution; Then pirfenidone is added in the solution, stirring obtains suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into suspension and carry out coating, obtain containing pill core after the drying;
Step 2, preparation slow release ball core: take by weighing the 200g celphere, 300g pirfenidone, 50g hymetellose; The 10g triethyl citrate, 5g Polyethylene Glycol, 5g phthalic acid ester; The 5g spermol, 20g Pulvis Talci, 10g silicon dioxide and 20g magnesium stearate; The framework material hymetellose is dissolved in the ethanol, is mixed with the framework material mass concentration and is 10% solution, add pirfenidone, plasticizer triethyl citrate, Polyethylene Glycol, phthalic acid ester and spermol then; With antiplastering aid Pulvis Talci, silicon dioxide and magnesium stearate, stirring obtains slow-release suspension; At last celphere is placed airpillow-dry granulator, in granulator, spray into slow-release suspension and carry out coating, obtain slow release ball core after the drying;
Step 3, preparation slow-release micro-pill:, obtain containing the slow-release micro-pill of pirfenidone with the slow release ball core mix homogeneously for preparing in pill core and the step 2 that contains for preparing in the step 1.
Embodiment 12
Present embodiment is identical with embodiment 11; Wherein difference is: said binding agent be in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch a kind of, three kinds or four kinds; Perhaps be two kinds in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30 and the sucrose; Perhaps being sodium carboxymethyl cellulose and starch, perhaps is 30 POVIDONE K 30 BP/USP 30 and starch; Said framework material is ethyl cellulose, cellulose acetate, hypromellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin or polyvinyl alcohol, perhaps is at least two kinds in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer be in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol a kind of, two or three; Said antiplastering aid is one or both in Pulvis Talci, silicon dioxide and the magnesium stearate.
Embodiment 13
The slow-release micro-pill of present embodiment is mixed by rapid release ball core and slow release ball core; Said rapid release ball core comprises 30% the pirfenidone that accounts for whole slow-release micro-pill quality, account for 1% porogen (microcrystalline Cellulose) of whole slow-release micro-pill quality and account for 1% binding agent (30 POVIDONE K 30 BP/USP 30) of whole slow-release micro-pill quality; Said slow release ball core is formed by containing pill core and being wrapped in the slow release layer that contains on the pill core; The said pill core that contains comprises 60% the pirfenidone that accounts for whole slow-release micro-pill quality, accounts for 2% porogen (microcrystalline Cellulose) of whole slow-release micro-pill quality and accounts for 2% binding agent (30 POVIDONE K 30 BP/USP 30) of whole slow-release micro-pill quality, and said slow release layer comprises 1% the framework material (ethyl cellulose) that accounts for whole slow-release micro-pill quality, account for 1% porogen (microcrystalline Cellulose) of whole slow-release micro-pill quality and account for 2% antiplastering aid (Pulvis Talci) of whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing 900g pirfenidone, 30g binding agent 30 POVIDONE K 30 BP/USP 30 and 30g porogen microcrystalline Cellulose; The pirfenidone that takes by weighing, binding agent and porogen mix homogeneously are obtained mixed powder; In the coating pan with the mixed powder input rotation of 2/7ths amounts; According to spraying purified water and the process cycling of adding the residue mixed powder, with the round as a ball glomeration granule of mixed powder; Then spherical particle is crossed 30 mesh sieves, the oversize after sieving is crossed 25 mesh sieves,, remove siftage and obtain containing pill core crossing siftage oven dry back behind 25 mesh sieves after 30 mesh sieves;
Step 2, preparation slow release ball core: take by weighing 10g framework material ethyl cellulose; 10g porogen microcrystalline Cellulose and 20g antiplastering aid Pulvis Talci; Framework material is dissolved in the ethanol; Be mixed with the framework material mass concentration and be 1%～10% solution, add porogen microcrystalline Cellulose and antiplastering aid Pulvis Talci then, stirring obtains the suspendible coating solution; 2/3rds in the pill core that contain with the step 1 preparation places airpillow-dry granulator at last, in granulator, sprays into the suspendible coating solution and carries out coating, obtains slow release ball core after the drying;
Step 3, preparation slow-release micro-pill: the residue for preparing in the step 1 1/3rd pastille ball cores as the slow release ball core mix homogeneously for preparing in rapid release ball core and the step 2, are obtained containing the slow-release micro-pill of pirfenidone.
Embodiment 14
Present embodiment is identical with embodiment 13, and wherein difference is: said binding agent is sodium carboxymethyl cellulose, sucrose or starch, perhaps is at least two kinds in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin or polyvinyl alcohol, perhaps is at least two kinds in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said porogen is Polyethylene Glycol or lactose, perhaps is at least two kinds in Polyethylene Glycol, microcrystalline Cellulose and the lactose; Said antiplastering aid is silicon dioxide or magnesium stearate, perhaps is at least two kinds in Pulvis Talci, silicon dioxide and the magnesium stearate.
Embodiment 15
The slow-release micro-pill of present embodiment is mixed by rapid release ball core and slow release ball core; Said rapid release ball core comprises 15% the pirfenidone that accounts for whole slow-release micro-pill quality, account for 5% porogen (2% Polyethylene Glycol, 2% microcrystalline Cellulose and 1% lactose) of whole slow-release micro-pill quality and account for 10% binding agent (4% sodium carboxymethyl cellulose, 4% 30 POVIDONE K 30 BP/USP 30 and 2% starch) of whole slow-release micro-pill quality; Said slow release ball core is formed by containing pill core and being wrapped in the slow release layer that contains on the pill core; The said pill core that contains comprises 30% the pirfenidone that accounts for whole slow-release micro-pill quality, accounts for 10% porogen (4% Polyethylene Glycol, 4% microcrystalline Cellulose and 2% lactose) of whole slow-release micro-pill quality and accounts for 20% binding agent (8% sodium carboxymethyl cellulose, 8% 30 POVIDONE K 30 BP/USP 30 and 4% starch) of whole slow-release micro-pill quality, and said slow release layer comprises 5% the framework material (2.5% hymetellose and 2.5% hydroxyethyl-cellulose) that accounts for whole slow-release micro-pill quality, account for 4% porogen (2% Polyethylene Glycol, 1% microcrystalline Cellulose and 1% lactose) of whole slow-release micro-pill quality and account for 1% antiplastering aid (silicon dioxide) of whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing the 450g pirfenidone; 300g binding agent (120g sodium carboxymethyl cellulose, 120g 30 POVIDONE K 30 BP/USP 30 and 60g starch); 150g porogen (60g Polyethylene Glycol, 60g microcrystalline Cellulose and 30g lactose); The pirfenidone that takes by weighing, binding agent and porogen mix homogeneously are obtained mixed powder; In the coating pan with the mixed powder input rotation of 2/7ths amounts, according to spraying purified water and the process cycling of adding the residue mixed powder, with the round as a ball glomeration granule of mixed powder; Then spherical particle is crossed 30 mesh sieves, the oversize after sieving is crossed 25 mesh sieves,, remove siftage and obtain containing pill core crossing siftage oven dry back behind 25 mesh sieves after 30 mesh sieves;
Step 2, preparation slow release ball core: take by weighing 50g framework material (25g hymetellose and 25g hydroxyethyl-cellulose); 40g porogen (20g Polyethylene Glycol, 10g microcrystalline Cellulose and 10g lactose) and 10g antiplastering aid (silicon dioxide); Framework material is dissolved in the purified water; Be mixed with the framework material mass concentration and be 1%～10% solution, add porogen and antiplastering aid then, stirring obtains the suspendible coating solution; 2/3rds in the pill core that contain with the step 1 preparation places airpillow-dry granulator at last, in granulator, sprays into the suspendible coating solution and carries out coating, obtains slow release ball core after the drying;
Step 3, preparation slow-release micro-pill: the residue for preparing in the step 1 1/3rd pastille ball cores as the slow release ball core mix homogeneously for preparing in rapid release ball core and the step 2, are obtained containing the slow-release micro-pill of pirfenidone.
Embodiment 16
Present embodiment is identical with embodiment 15; Wherein difference is: said binding agent be in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch a kind of, two kinds or four kinds; Perhaps be sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30 and sucrose; Perhaps being sodium carboxymethyl cellulose, sucrose and starch, perhaps is 30 POVIDONE K 30 BP/USP 30, sucrose and starch; Said framework material is a kind of in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol or more than three kinds; Perhaps being two kinds in ethyl cellulose, cellulose acetate, hypromellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol, perhaps is the mixture of a kind of and hymetellose in ethyl cellulose, cellulose acetate, hypromellose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said porogen is one or both in Polyethylene Glycol, microcrystalline Cellulose and the lactose; Said antiplastering aid is Pulvis Talci or magnesium stearate, perhaps is at least two kinds in Pulvis Talci, silicon dioxide and the magnesium stearate.
Embodiment 17
The slow-release micro-pill of present embodiment is mixed by rapid release ball core and slow release ball core; Said rapid release ball core comprises 20% the pirfenidone that accounts for whole slow-release micro-pill quality, account for 4% porogen (3% microcrystalline Cellulose and 1% lactose) of whole slow-release micro-pill quality and account for 5% binding agent (2% sodium carboxymethyl cellulose and 3% 30 POVIDONE K 30 BP/USP 30) of whole slow-release micro-pill quality; Said slow release ball core is formed by containing pill core and being wrapped in the slow release layer that contains on the pill core; The said pill core that contains comprises 40% the pirfenidone that accounts for whole slow-release micro-pill quality, accounts for 8% porogen (6% microcrystalline Cellulose and 2% lactose) of whole slow-release micro-pill quality and accounts for 10% binding agent (4% sodium carboxymethyl cellulose and 6% 30 POVIDONE K 30 BP/USP 30) of whole slow-release micro-pill quality, and said slow release layer comprises 3% the framework material (1% acroleic acid resin and 2% polyvinyl alcohol) that accounts for whole slow-release micro-pill quality, account for 5% porogen (3% microcrystalline Cellulose and 2% lactose) of whole slow-release micro-pill quality and account for 5% antiplastering aid (2% Pulvis Talci, 1% silicon dioxide and 2% magnesium stearate) of whole slow-release micro-pill quality.
The method for preparing of the slow-release micro-pill of present embodiment is:
Step 1, preparation contain pill core: take by weighing 600g pirfenidone, 150g binding agent (60g sodium carboxymethyl cellulose and 90g 30 POVIDONE K 30 BP/USP 30) and 120g porogen (90g microcrystalline Cellulose and 30g lactose); The pirfenidone that takes by weighing, binding agent and porogen mix homogeneously are obtained mixed powder; In the coating pan with the mixed powder input rotation of 2/7ths amounts; According to spraying purified water and the process cycling of adding the residue mixed powder, with the round as a ball glomeration granule of mixed powder; Then spherical particle is crossed 30 mesh sieves, the oversize after sieving is crossed 25 mesh sieves,, remove siftage and obtain containing pill core crossing siftage oven dry back behind 25 mesh sieves after 30 mesh sieves;
Step 2, preparation slow release ball core: take by weighing 30g framework material (10g acroleic acid resin and 20g polyvinyl alcohol); 50g porogen (30g microcrystalline Cellulose and 20g lactose) and 50g antiplastering aid (20g Pulvis Talci, 10g silicon dioxide and 20g magnesium stearate); Framework material is dissolved in the ethanol; Be mixed with the framework material mass concentration and be 1%～10% solution, add porogen and antiplastering aid then, stirring obtains the suspendible coating solution; 2/3rds in the pill core that contain with the step 1 preparation places airpillow-dry granulator at last, in granulator, sprays into the suspendible coating solution and carries out coating, obtains slow release ball core after the drying;
Step 3, preparation slow-release micro-pill: the residue for preparing in the step 1 1/3rd pastille ball cores as the slow release ball core mix homogeneously for preparing in rapid release ball core and the step 2, are obtained containing the slow-release micro-pill of pirfenidone.
Embodiment 18
Present embodiment is identical with embodiment 17; Wherein difference is: said binding agent be in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch a kind of, three kinds or four kinds; Perhaps being two kinds in sodium carboxymethyl cellulose, sucrose and the starch, perhaps is the mixture of a kind of and 30 POVIDONE K 30 BP/USP 30 in sucrose and the starch; Said framework material is a kind of in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol or more than three kinds; Perhaps being two kinds in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose and the polyvinyl alcohol, perhaps is the mixture of a kind of and acroleic acid resin in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose and the methylcellulose; Said porogen is a kind of in Polyethylene Glycol, microcrystalline Cellulose and the lactose or three kinds, perhaps is Polyethylene Glycol and lactose, perhaps is Polyethylene Glycol and microcrystalline Cellulose; Said antiplastering aid is one or both in Pulvis Talci, silicon dioxide and the magnesium stearate.
Release degree to the slow-release micro-pill that contains pirfenidone of the embodiment of the invention 1, embodiment 3, embodiment 5, embodiment 7, embodiment 9, embodiment 11, embodiment 13, embodiment 15 and embodiment 17 is measured, and assay method is: according to drug release determination method (two appendix X of Chinese Pharmacopoeia version in 2010 D, first method), i.e. oar method; Sample thief is a dissolution medium with 900mL water, and rotating speed is 75rpm; Operation in accordance with the law at 2h, 4h, 6h, 8h, 10h, 12h time point, is got solution 10mL respectively and is filtered; While supplementing water 10mL, precision is measured in filtrating 3mL to the 50mL volumetric flask, and thin up is to scale; As need testing solution, it is an amount of that in addition precision takes by weighing the pirfenidone reference substance, be dissolved in water and quantitatively dilution process the solution that contains 15 μ g pirfenidones among every 1mL; As reference substance solution, use ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2010 A) then, be that the 316nm place surveys trap at wavelength; Calculate the release degree, the result sees the following form:
Table 1 contains the release degree testing result of the slow-release micro-pill of pirfenidone
| Detection time | 2h | 4h | 6h | 8h | 10h | 12h |
| Embodiment 1 | 11.6％ | 38.7％ | 51.3％ | 62.4％ | 85.7％ | 92.4％ |
| Embodiment 3 | 15.4％ | 29.8％ | 50.7％ | 70.7％ | 81.3％ | 90.8％ |
| Embodiment 5 | 14.9％ | 21.3％ | 42.1％ | 79.1％ | 87.3％ | 94.9％ |
| Embodiment 7 | 18.1％ | 27.4％ | 46.9％ | 75.4％ | 85.9％ | 92.7％ |
| Embodiment 9 | 17.7％ | 31.3％ | 54.8％ | 73.7％ | 89.3％ | 96.2％ |
| Embodiment 11 | 19.2％ | 33.4％ | 56.9％ | 80.1％ | 88.6％ | 96.8％ |
| Embodiment 13 | 18.2％ | 30.4％ | 48.2％ | 74.2％ | 83.2％ | 94.2％ |
| Embodiment 15 | 16.5％ | 31.2％ | 51.5％ | 75.8％ | 84.7％ | 95.6％ |
| Embodiment 17 | 17.2％ | 29.8％ | 43.5％ | 79.5％ | 83.5％ | 97.2％ |
Can find out that from table 1 slow-release micro-pill that contains pirfenidone of the present invention discharges slowly sustainable release 12h; Both can make medicine reach therapeutic effect rapidly; Can keep long action time again, blood drug level is steady, can effectively reduce the patient take medicine frequency with take medicine quantity.
The above; It only is preferred embodiment of the present invention; Be not that the present invention is done any restriction, every technical spirit changes any simple modification, change and the equivalent structure that above embodiment did according to the present invention, all still belongs in the protection domain of technical scheme of the present invention.
Claims (7)
1. a slow-release micro-pill that contains pirfenidone is characterized in that, said slow-release micro-pill is the slow-release micro-pill of being processed by pirfenidone and pharmaceutically acceptable auxiliary material; The quality percentage composition of pirfenidone is 15%～90% in the said slow-release micro-pill, and surplus is auxiliary material.
2. a kind of slow-release micro-pill that contains pirfenidone according to claim 1 is characterized in that said slow-release micro-pill comprises celphere, medicine layer, slow release layer and pastille release layer from inside to outside successively; The quality percentage composition of said slow-release micro-pill empty ball core is 30%～60%; Said medicine layer comprises 10%～50% the pirfenidone that accounts for whole slow-release micro-pill quality and 1%～10% the binding agent that accounts for whole slow-release micro-pill quality; Said slow release layer comprises 1%～5% the framework material that accounts for whole slow-release micro-pill quality, 0.5%～2.5% plasticizer that accounts for whole slow-release micro-pill quality and 1%～5% the antiplastering aid that accounts for whole slow-release micro-pill quality; Said pastille release layer comprises 5%～30% the pirfenidone that accounts for whole slow-release micro-pill quality and 1%～5% the binding agent that accounts for whole slow-release micro-pill quality.
3. a kind of slow-release micro-pill that contains pirfenidone according to claim 2; It is characterized in that; Said binding agent is one or more in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is one or more in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is one or more in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol, and said antiplastering aid is one or more in Pulvis Talci, silicon dioxide and the magnesium stearate.
4. a kind of slow-release micro-pill that contains pirfenidone according to claim 1 is characterized in that, said slow-release micro-pill is by containing pill core and slow release ball core mixes; The said pill core that contains is made up of celphere and the medicine layer that is wrapped on the celphere; Wherein celphere accounts for 20%～40% of whole slow-release micro-pill quality, and said medicine layer comprises 10%～50% the pirfenidone that accounts for whole slow-release micro-pill quality and 1%～30% the binding agent that accounts for whole slow-release micro-pill quality; Said slow release ball core is made up of celphere and the pastille slow-release layer that is wrapped on the celphere; Wherein celphere accounts for 10%～20% of whole slow-release micro-pill quality, said pastille slow-release layer comprises 5%～30% the pirfenidone that accounts for whole slow-release micro-pill quality, account for whole slow-release micro-pill quality 1%～5% framework material, account for 0.5%～2.5% plasticizer of whole slow-release micro-pill quality and account for 1%～5% antiplastering aid of whole slow-release micro-pill quality.
5. a kind of slow-release micro-pill that contains pirfenidone according to claim 4; It is characterized in that; Said binding agent is one or more in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is one or more in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said plasticizer is one or more in triethyl citrate, Polyethylene Glycol, phthalic acid ester and the spermol, and said antiplastering aid is one or more in Pulvis Talci, silicon dioxide and the magnesium stearate.
6. a kind of slow-release micro-pill that contains pirfenidone according to claim 1 is characterized in that, said slow-release micro-pill is mixed by rapid release ball core and slow release ball core; Said rapid release ball core comprises 15%～30% the pirfenidone that accounts for whole slow-release micro-pill quality, account for 1%～5% porogen of whole slow-release micro-pill quality and account for 1%～10% binding agent of whole slow-release micro-pill quality; Said slow release ball core is formed by containing pill core and being wrapped in the slow release layer that contains on the pill core; The said pill core that contains comprises 30%～60% the pirfenidone that accounts for whole slow-release micro-pill quality, accounts for 2%～10% porogen of whole slow-release micro-pill quality and accounts for 2%～20% binding agent of whole slow-release micro-pill quality, and said slow release layer comprises 1%～5% the framework material that accounts for whole slow-release micro-pill quality, account for 1%～5% porogen of whole slow-release micro-pill quality and account for 1%～5% antiplastering aid of whole slow-release micro-pill quality.
7. a kind of slow-release micro-pill that contains pirfenidone according to claim 6; It is characterized in that; Said binding agent is one or more in sodium carboxymethyl cellulose, 30 POVIDONE K 30 BP/USP 30, sucrose and the starch; Said framework material is one or more in ethyl cellulose, cellulose acetate, hypromellose, hymetellose, hydroxyethyl-cellulose, methylcellulose, acroleic acid resin and the polyvinyl alcohol; Said porogen is one or more in Polyethylene Glycol, microcrystalline Cellulose and the lactose, and said antiplastering aid is one or more in Pulvis Talci, silicon dioxide and the magnesium stearate.
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| CN2011104310588A CN102488660A (en) | 2011-12-15 | 2011-12-15 | Sustained-release pellet containing pirfeudone |
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| CN107080741A (en) * | 2017-04-28 | 2017-08-22 | 北京工业大学 | Pirfenidone sustained release preparation and preparation method |
| CN108938601A (en) * | 2018-08-15 | 2018-12-07 | 珠海润都制药股份有限公司 | A kind of metformin hydrochloride enteric-coated sustained release pellet and preparation method thereof |
| CN110248646A (en) * | 2016-11-11 | 2019-09-17 | 细胞治疗技术合伙股份有限公司 | Slow releasing composition comprising pirfenidone is used to treat and reverse the medicinal usage of people's steatohepatitis (NAFLD/NASH) |
| US11766426B2 (en) | 2012-03-28 | 2023-09-26 | Excalibur Pharmaceuticals, Inc. | Semi-solid topical composition containing pirfenidone and modified diallyl disulfide oxide (M-DDO) for eliminating or preventing acne |
| US11779574B2 (en) | 2007-08-14 | 2023-10-10 | Excalibur Pharmaceuticals, Inc. | Gel containing pirfenidone |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11779574B2 (en) | 2007-08-14 | 2023-10-10 | Excalibur Pharmaceuticals, Inc. | Gel containing pirfenidone |
| US11766426B2 (en) | 2012-03-28 | 2023-09-26 | Excalibur Pharmaceuticals, Inc. | Semi-solid topical composition containing pirfenidone and modified diallyl disulfide oxide (M-DDO) for eliminating or preventing acne |
| CN110248646A (en) * | 2016-11-11 | 2019-09-17 | 细胞治疗技术合伙股份有限公司 | Slow releasing composition comprising pirfenidone is used to treat and reverse the medicinal usage of people's steatohepatitis (NAFLD/NASH) |
| CN106619734A (en) * | 2016-12-15 | 2017-05-10 | 湖南中健欣元生物科技有限公司 | Royal jelly pellet lozenge and preparation method thereof |
| CN106619734B (en) * | 2016-12-15 | 2019-09-03 | 湖南中健欣元生物科技有限公司 | A kind of royal jelly pellet lozenge and preparation method thereof |
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| WO2023208241A1 (en) * | 2022-04-29 | 2023-11-02 | 越洋医药开发(广州)有限公司 | Pirfenidone sustained-release oral solid preparation |
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