CN1771911B - Re-dispersible nanometer particle of insoluble medicine and its preparation - Google Patents
Re-dispersible nanometer particle of insoluble medicine and its preparation Download PDFInfo
- Publication number
- CN1771911B CN1771911B CN 200510061510 CN200510061510A CN1771911B CN 1771911 B CN1771911 B CN 1771911B CN 200510061510 CN200510061510 CN 200510061510 CN 200510061510 A CN200510061510 A CN 200510061510A CN 1771911 B CN1771911 B CN 1771911B
- Authority
- CN
- China
- Prior art keywords
- sirolimus
- nanoparticle
- nanometer particle
- protective agent
- redispersible
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000003814 drug Substances 0.000 title claims abstract description 115
- 239000002245 particle Substances 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 239000008187 granular material Substances 0.000 claims abstract description 51
- 239000000843 powder Substances 0.000 claims abstract description 45
- 238000004108 freeze drying Methods 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000003223 protective agent Substances 0.000 claims abstract description 28
- 238000001694 spray drying Methods 0.000 claims abstract description 26
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims abstract description 19
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims abstract description 19
- 229960002930 sirolimus Drugs 0.000 claims abstract description 19
- 239000002775 capsule Substances 0.000 claims abstract description 3
- 239000003826 tablet Substances 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims description 37
- 239000000725 suspension Substances 0.000 claims description 36
- 239000002105 nanoparticle Substances 0.000 claims description 28
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 16
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 15
- 229930195725 Mannitol Natural products 0.000 claims description 15
- 239000000594 mannitol Substances 0.000 claims description 15
- 235000010355 mannitol Nutrition 0.000 claims description 15
- 239000012153 distilled water Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 9
- 238000007710 freezing Methods 0.000 claims description 9
- 230000008014 freezing Effects 0.000 claims description 9
- 229920001993 poloxamer 188 Polymers 0.000 claims description 9
- 229940044519 poloxamer 188 Drugs 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 8
- 229920001983 poloxamer Polymers 0.000 claims description 7
- 229960000502 poloxamer Drugs 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 238000009413 insulation Methods 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 238000005057 refrigeration Methods 0.000 claims description 5
- 230000000630 rising effect Effects 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims 2
- 229940067606 lecithin Drugs 0.000 claims 2
- 235000010445 lecithin Nutrition 0.000 claims 2
- 239000000787 lecithin Substances 0.000 claims 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 2
- 230000015271 coagulation Effects 0.000 abstract 1
- 238000005345 coagulation Methods 0.000 abstract 1
- 239000006185 dispersion Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 229940126589 solid medicine Drugs 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 15
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 238000007865 diluting Methods 0.000 description 8
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000002159 nanocrystal Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000008342 pharmaceutical dispersion Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention provides one kind of re-dispersible nanometer particle powder of insoluble medicine sirolimus and its preparation process. The re-dispersible nanometer medicine particle powder consists of nanometer sirolimus particle 0.6-100 wt%, freeze drying protecting agent 0-99.3 wt% and spray drying protecting agent 0-96.4 wt%, and has average particle size after re-dispersion in water of 1000 nm. The nanometer medicine particle powder is prepared through freeze drying process or spray drying process suitable for industrial production. The preparation process has less coagulation of nanometer particle, and the prepared nanometer medicine particle powder may be used in preparing nanometer solid medicine preparations, including tablet, capsule, granule, etc.
Description
Technical field
The invention belongs to redispersible Nano medication manufacturing method of power, relate to the dry compositions screening and the manufacture method of insoluble drug sirolimus nanoparticle suspension.
Background technology
Developing rapidly of nanosecond science and technology greatly promotes the great discovery and the technological revolution in fields such as biotechnology, information technology, caused the great-leap-forward development of nanometer biotechnology and relevant medicinal industry thereof.With " medicine and therapeutic gene nanometer formulation " is the nano-drug preparation theory and the technology of core, is faced with historical opportunity to develop.
Adopt nanotechnology, can greatly increase the specific surface area of water-insoluble drug, improve the dissolution of medicine in body fluid, thereby significantly improve bioavailability of medicament, reduce individual variation, reduce toxic and side effects." Elan Inc. " company has adopted a kind of technology platform that is called as nanocrystal technology (NanoCrystal technology), with a kind of special grinding technology the particle diameter of medicine is reduced to extremely little scope (diameter≤400nm).The sirolimus nanometer sheet that " Elan Inc. " company adopts this technology to produce, approval and list marketing in calendar year 2001 acquisition U.S. FDA become U.S. FDA first granted " nanometer formulation " since the dawn of human civilization.
The Nano medication powder is the basis that follow-up nano-solid preparation is made.By suitable prescription and Technology, the medicament nano granule suspension is manufactured the Nano medication powder that possesses redispersibility, be the basis that Nano medication is really realized industrialization.
Lyophilization and spray drying technology are that liquid or semi-solid form pharmaceutical dispersions create solid forms medicine common method.In the states of matter transformation process of Nano medication powder, its core is the Nano medication powder for preparing at the medicament nano granule suspension, and the diameter of aspirin particle behind the redispersion must be similar or approaching to dry preceding diameter of aspirin particle.Only in this way, could realize the suitability for industrialized production of nanometer formulation product, safe and effective when guaranteeing clinical practice.
Yet, in the Nano medication powder manufacturing technology field of redispersibility, lack system always and effectively explore and research, also lack its corresponding theory and instruct.The redispersibility of Nano medication powder has become a major issue that restricts the Nano medication industrialization at present.Along with the development of nanometer formulation technology, solve this technical problem more apparent urgent.
" a kind of indissoluble medicament nano granule and preparation method thereof " (number of patent application 200510061371.1) described the preparation of insoluble drug sirolimus nanoparticle suspension; with " solvent diffuse-high pressure breast is even " technology; select suitable nanoparticle protective agent, its medicament nano granule particle diameter is controlled in the 500nm.
Based on the nanoparticle that method for preparing obtains, only rely on nanoparticle coating material (surfactant), be difficult to realize the stability of medicament nano granule.Adopt common lyophilization or spray drying process, but adhesion between the associated particle crystallization and growth cause the disappearance of quick redispersibility.The invention describes and adopt lyophilization or spray drying technology, can keep the original particle diameter of medicament nano granule in manufacturing, and the application that realizes aspects such as quick redispersion characteristic.
Summary of the invention
An object of the present invention is to provide a kind of redispersible nanometer particle of insoluble medicine; form by sirolimus nanoparticle and lyophilization or spray drying protective agent poloxamer 188, mannitol, polyvinylpyrrolidone K30; the weight percentage of sirolimus nanoparticle is 0.6%～100%; protective agent poloxamer 1880%～99.3%; mannitol 0%～93.8%, polyvinylpyrrolidone K30 0%～40.9%.
Medicament nano granule powder provided by the invention, behind the chance water redispersion, its mean diameter is less than 1000nm, or after meeting the water redispersion, its mean diameter is less than 500nm.
Freezing drying protective agent is selected one or more the mixture in polyvinylpyrrolidone k30, poloxamer, mannitol, sorbitol, lactose, sucrose, glucose, the trehalose for use, and its consumption is 0%～99.3% (w/w) of total solid.
The spray drying protective agent is selected one or more the mixture in polyvinylpyrrolidone k30, poloxamer, mannitol, sorbitol, lactose, sucrose, glucose, the trehalose for use, and its consumption is 0～96.4% (w/w) of total solid.
Freezing drying protective agent consists of poloxamer 188 0%～99.3% (w/w), mannitol 0%～90.0% (w/w), polyvinylpyrrolidone k30 0%～40.9% (w/w).
The spray drying protective agent consists of poloxamer 188 0%～43.0% (w/w), mannitol 0%～93.8% (w/w), polyvinylpyrrolidone k30 0%～27.9% (w/w).
Second purpose of the present invention provides the preparation method of redispersibility nanorize medical solid powder, is achieved through the following technical solutions:
(1) freeze-drying preparation: get the medicament nano granule suspension that obtains according to application number 200510061371.1 disclosed methods; after adding the freezing drying protective agent dissolving; place the lyophilizing dish; liquid level is 2～3cm; put on the flaggy of lyophilization mechanical goods chamber; about 6～7 hours of-45 ℃ of pre-freezes; open water vessel refrigeration switch, finish the back in the pre-freeze insulation and open vacuum pump, when the vacuum reading is reduced to 10 handkerchiefs when following; the goods room temperature that raises gradually is to-5 ℃; be incubated about 24～30 hours, when products temperature and flaggy temperature near the time, continue rising flaggy temperature to about 35 ℃ and be incubated 3 hours; lyophilization is about 34 hours altogether, obtains the Nano medication powder.Medicament nano granule powder through freeze-drying prepares can form medicament nano granule by redispersion in distilled water.
(2) spray drying method for preparation: get the medicament nano granule suspension that obtains according to application number 200510061371.1 disclosed methods; add the dissolving of spray drying protective agent respectively; control spray-dired inlet temperature: 130 ℃; leaving air temp: 85 ℃; material flow: 5ml/min; air velocity 600L/min collects and obtains the Nano medication powder.The medicament nano granule powder that spray-dried method prepares can form medicament nano granule by redispersion in distilled water.
Redispersible medicament nano granule powder provided by the invention can prepare the Nano medication solid preparation, and dosage form is tablet, capsule, granule etc.
This medicament nano granule provided by the invention and redispersible medicament nano granule powder, composition is simple, method is practical reliable.Selected main adjuvant poloxamer 188, mannitol, polyvinylpyrrolidone K30 etc. are common medicinal supplementary material.The medicament nano granule manufacture method adopts solvent diffuse-high pressure newborn even, but suitability for industrialized production.Redispersion medicament nano granule manufacturing method of power adopts lyophilization and spray drying, possesses the industrialization prospect of production.
The present invention is to provide a kind of new indissoluble medicament nano granule suspension lyophilization or spray drying and form, comprise lyophilization or spray drying protective agent composition that the nanoparticle particle is provided, can reduce the cohesion of nanoparticle in lyophilizing or the dried process of spray.The present invention provides simultaneously and has used these protectant concrete grammars.
The specific embodiment
The present invention is further described in conjunction with the embodiments.
Embodiment one: the freeze-drying preparation of medicament nano granule powder
Get the medicament nano granule suspension that obtains according to application number 200510061371.1 disclosed methods; with distilled water diluting or without dilution; add poloxamer 188 dissolvings; place the lyophilizing dish; liquid level is 2～3cm; put on the flaggy of lyophilization mechanical goods chamber, about 6～7 hours of-45 ℃ of pre-freezes are opened water vessel refrigeration switch; finish the back in the pre-freeze insulation and open vacuum pump; reduce to 10 handkerchiefs when following when the vacuum reading, the goods room temperature that raises gradually is incubated about 24～30 hours to-5 ℃; when products temperature and flaggy temperature near the time; continue rising flaggy temperature to about 35 ℃ and be incubated 3 hours, lyophilization is about 34 hours altogether, obtains the Nano medication powder.
Nano medication powder adding distil water is diluted to the preceding same medicine concentration of lyophilizing; hand vibration 1min redispersion; medicament nano granule suspension behind the redispersion continues with 20 times of distilled water dilutings or without dilution, with Zetasizer 3000HS analysis-e/or determining particle diameter and surface potential (referring to table 1).
Result of study shows, the direct lyophilization of medicament nano granule suspension, and the particle diameter behind the freeze-dried powder redispersion significantly increases.Add the protective agent poloxamer in the medicament nano granule suspension, along with the decline of suspension Chinese medicine concentration, the particle diameter of medicament nano granule reduces gradually behind the freeze-dried powder redispersion.Therefore, when lyophilization, need to add an amount of freezing drying protective agent poloxamer, the concentration of suspension Chinese medicine is controlled at 5mg/ml and following.
Size ratio is than (g/100ml) before and after the lyophilization of table 1 different pharmaceutical concentration nanoparticle suspension
Embodiment two: the freeze-drying preparation of medicament nano granule powder
Get the medicament nano granule suspension that obtains according to application number 200510061371.1 disclosed methods; it is 5mg/mL that adding distil water is diluted to drug level; adding recipe quantity mannitol and polyvinylpyrrolidone K30 respectively dissolves as freeze drying protectant (referring to table 2); place the lyophilizing dish, liquid level is 2～3cm.Put on the flaggy of lyophilization mechanical goods chamber, about 6～7 hours of-45 ℃ of pre-freezes, open water vessel refrigeration switch, finish the back in the pre-freeze insulation and open vacuum pump, when the vacuum reading is reduced to 10 handkerchiefs when following, the goods room temperature that raises gradually is to-5 ℃, be incubated about 24～30 hours, when products temperature and flaggy temperature near the time, continue rising flaggy temperature to about 35 ℃ and be incubated 3 hours, lyophilization is about 34 hours altogether, obtains the Nano medication powder.
Nano medication powder adding distil water is diluted to the preceding same medicine concentration of lyophilizing, hand vibration 1min redispersion.Medicament nano granule suspension behind the redispersion continues with 20 times of distilled water dilutings, with Zetasizer3000HS analysis-e/or determining particle diameter and surface potential (referring to table 2).
Size ratio before and after the lyophilization of table 2 drug level 5mg/mL nanoparticle suspension
Result of study shows, under high drug level condition, adopts recipe quantity mannitol and polyvinylpyrrolidone k30 as freeze drying protectant, and the medicament nano granule particle diameter of redispersion is significantly increased after the freeze-dried powder lyophilizing.
Embodiment three: the freeze-drying preparation of medicament nano granule powder
Get the medicament nano granule suspension that obtains according to application number 200510061371.1 disclosed methods; with distilled water diluting to drug level 2mg/mL; add recipe quantity poloxamer 188 respectively; mannitol and polyvinylpyrrolidone k30 dissolve as freeze drying protectant (referring to table 3); place the lyophilizing dish; liquid level is 2～3cm; put on the flaggy of lyophilization mechanical goods chamber; about 6～7 hours of-45 ℃ of pre-freezes; open water vessel refrigeration switch; finish the back in the pre-freeze insulation and open vacuum pump; reduce to 10 handkerchiefs when following when the vacuum reading, the goods room temperature that raises gradually is incubated about 24～30 hours to-5 ℃; when products temperature and flaggy temperature near the time; continue rising flaggy temperature to about 35 ℃ and be incubated 3 hours, lyophilization is about 34 hours altogether, obtains the Nano medication powder.
Nano medication powder adding distil water is diluted to the preceding same medicine concentration of lyophilizing, hand vibration 1min redispersion.Medicament nano granule suspension behind the redispersion continues with 20 times of distilled water dilutings, with Zetasizer3000HS analysis-e/or determining particle diameter (referring to table 3).
Result of study shows, reducing under the drug level condition, adopts suitable freezing drying protective agent, can obviously improve the particle diameter behind the freeze-dried powder redispersion.
Size ratio before and after the lyophilization of table 3 drug level 2mg/mL nanoparticle suspension
Embodiment four: the spray drying method for preparation of medicament nano granule powder
Get the medicament nano granule suspension that obtains according to application number 200510061371.1 disclosed methods; with distilled water diluting or without dilution; add mannitol; dissolving; control spray-dired inlet temperature: 130 ℃, leaving air temp: 85 ℃, material flow: 5ml/min; air velocity 600L/min collects and obtains the Nano medication powder.
Nano medication powder adding distil water is diluted to spray and does preceding same medicine concentration; hand vibration 1min redispersion; medicament nano granule suspension behind the redispersion continues with 20 times of distilled water dilutings or without dilution, with Zetasizer 3000HS analysis-e/or determining particle diameter (referring to table 4).
Result of study shows, the direct spray drying of medicament nano granule suspension, and the particle diameter behind the nanoparticle redispersion significantly increases.Add protective agent mannitol in the medicament nano granule suspension, along with the decline of suspension Chinese medicine concentration, the particle diameter of nanoparticle reduces gradually behind the freeze-dried powder redispersion.When the concentration of medicament nano granule suspension Chinese medicine is controlled at 5mg/ml and following, add spray drying after an amount of protective agent, can obtain the medicament nano granule powder of redispersion particle diameter＜500nm.
Size ratio is than (g/100ml) before and after the table 4 different pharmaceutical concentration nanoparticle suspension spray drying
Embodiment five: the spray drying method for preparation of medicament nano granule powder
Get the medicament nano granule suspension that obtains according to application number 200510061371.1 disclosed methods; it is 5mg/mL that adding distil water is diluted to drug level; add recipe quantity poloxamer 188, mannitol and polyvinylpyrrolidone K30 respectively as the dried protective agent of spray (referring to table 5) dissolving; control spray-dired inlet temperature: 130 ℃; leaving air temp: 85 ℃; material flow: 5ml/min, air velocity 600L/min collects and obtains the Nano medication powder.
Nano medication powder adding distil water is diluted to spray and does preceding same medicine concentration, hand vibration 1min redispersion, and the medicament nano granule suspension behind the redispersion continues with 20 times of distilled water dilutings, with Zetasizer3000HS analysis-e/or determining particle diameter (referring to table 5).
Result of study shows; to prepare the indissoluble medicament nano granule suspension according to the method that number of patent application 200510061371.1 provides, to be diluted to drug level be 5mg/mL; select suitable spray drying protective agent, can significantly improve the particle diameter behind the nanoparticle redispersion.
The different spray drying protective agents of table 5 are to spraying the influence of doing front and back medicament nano granule particle diameter
Need not further to elaborate, believe and adopt the disclosed content in front, those skilled in the art can use the present invention to greatest extent.Therefore, the embodiment of front is interpreted as only illustrating, but not limits the scope of the invention by any way.
Claims (8)
1. redispersible nanometer particle of insoluble medicine, it is characterized in that: form by sirolimus nanoparticle and freezing drying protective agent, its weight percentage is, sirolimus nanoparticle 0.6%～100%, freezing drying protective agent 0～99.3%, two constituent content sums are 100%, and the mean diameter behind this nanoparticle powder chance water redispersion is less than 1000nm;
Described redispersible nanometer particle of insoluble medicine adopts freeze-drying method to prepare, described sirolimus nanoparticle derives from sirolimus nanoparticle suspension, this suspension is in every milliliter, the amount of sirolimus is 10mg or 5mg or 2mg or 1mg or 0.2mg or 0.1mg, and sirolimus: lecithin: the weight ratio of poloxamer 188 is 1.0: 0.1: 0.225;
Described freezing drying protective agent weight percent consists of poloxamer 1880%～99.3%, mannitol 0%～90.0%, and polyvinylpyrrolidone k300%～40.9%, each constituent content sum is 100%.
2. redispersible nanometer particle of insoluble medicine, it is characterized in that: form by sirolimus nanoparticle and spray drying protective agent, its weight percentage is, sirolimus nanoparticle 0.6%～100%, spray drying protective agent 0～96.4%, two constituent content sums are 100%, and the mean diameter behind this nanoparticle powder chance water redispersion is less than 1000nm;
Described redispersible nanometer particle of insoluble medicine adopts spray drying process to prepare, described sirolimus nanoparticle derives from sirolimus nanoparticle suspension, this suspension is in every milliliter, the amount of sirolimus is 10mg or 5mg or 2mg or 1mg or 0.2mg or 0.1mg, and sirolimus: lecithin: the weight ratio of poloxamer 188 is 1.0: 0.1: 0.225;
Described spray drying protective agent weight percent consists of poloxamer 1880%～43.0%, mannitol 0%～93.8%, and polyvinylpyrrolidone k300%～27.9%, each constituent content sum is 100%.
3. a method for preparing the described redispersible nanometer particle of insoluble medicine of claim 1 is characterized in that the freeze-drying method preparation, realizes by following steps:
The thing nanoparticle suspension of getting it filled; add freezing drying protective agent; dissolving; place the lyophilizing dish; liquid level is 2～3cm; put on the flaggy of lyophilization mechanical goods chamber ,-45 ℃ of pre-freezes 6～7 hours are opened water vessel refrigeration switch; finish the back in the pre-freeze insulation and open vacuum pump; reduce to 10 handkerchiefs when following when the vacuum reading, the goods room temperature that raises gradually is incubated 24～30 hours to-5 ℃; when products temperature and flaggy temperature near the time; continue rising flaggy temperature to 35 ℃ and be incubated 3 hours, lyophilization is 34 hours altogether, obtains the Nano medication powder.
4. a method for preparing the described redispersible nanometer particle of insoluble medicine of claim 2 is characterized in that the spray drying process preparation, realizes by following steps:
The thing nanoparticle suspension of getting it filled adds the dissolving of spray drying protective agent, controls spray-dired inlet temperature: 130 ℃, and leaving air temp: 85 ℃, material flow: 5ml/min, air velocity 600L/min collects and obtains the Nano medication powder.
5. the preparation method of a kind of redispersible nanometer particle of insoluble medicine according to claim 3 is characterized in that: through the medicament nano granule powder that freeze-drying prepares, redispersion forms medicament nano granule in distilled water.
6. the preparation method of a kind of redispersible nanometer particle of insoluble medicine according to claim 4 is characterized in that: the medicament nano granule powder that spray-dried method prepares, redispersion forms medicament nano granule in distilled water.
7. each described a kind of redispersible nanometer particle of insoluble medicine application in preparation Nano medication solid preparation of claim 1-2.
8. application according to claim 7 is characterized in that: dosage form is tablet, capsule, granule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510061510 CN1771911B (en) | 2005-11-10 | 2005-11-10 | Re-dispersible nanometer particle of insoluble medicine and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510061510 CN1771911B (en) | 2005-11-10 | 2005-11-10 | Re-dispersible nanometer particle of insoluble medicine and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1771911A CN1771911A (en) | 2006-05-17 |
| CN1771911B true CN1771911B (en) | 2010-05-12 |
Family
ID=36759166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510061510 Active CN1771911B (en) | 2005-11-10 | 2005-11-10 | Re-dispersible nanometer particle of insoluble medicine and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1771911B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100427584C (en) * | 2006-08-11 | 2008-10-22 | 江南大学 | Plant lactobacillus and method of biological preparing conjugated linoleic acid using the same |
| CN107049963B (en) * | 2017-06-23 | 2020-11-03 | 北京化工大学 | Sirolimus nano-drug composition and preparation method thereof |
| CN114869852A (en) * | 2021-12-28 | 2022-08-09 | 青岛润达生物科技有限公司 | Preparation method for improving antioxidant activity of ganoderma lucidum polysaccharide powder and protective agent |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475205A (en) * | 2002-08-15 | 2004-02-18 | 刘云清 | Medicine conveying system--preparation method of solid nano medicine |
| CN1493361A (en) * | 2003-08-29 | 2004-05-05 | 上海医药工业研究院 | Lipid nano-particle of glyceride behenate and its preparation method |
| CN1493278A (en) * | 2003-08-29 | 2004-05-05 | 上海医药工业研究院 | Silymarin behenic acid glyceride lipid nano particle oral solution dosage and its preparation method |
| CN1568938A (en) * | 2003-07-22 | 2005-01-26 | 范敏华 | Nanometer emulsion and preparation method thereof |
-
2005
- 2005-11-10 CN CN 200510061510 patent/CN1771911B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475205A (en) * | 2002-08-15 | 2004-02-18 | 刘云清 | Medicine conveying system--preparation method of solid nano medicine |
| CN1568938A (en) * | 2003-07-22 | 2005-01-26 | 范敏华 | Nanometer emulsion and preparation method thereof |
| CN1493361A (en) * | 2003-08-29 | 2004-05-05 | 上海医药工业研究院 | Lipid nano-particle of glyceride behenate and its preparation method |
| CN1493278A (en) * | 2003-08-29 | 2004-05-05 | 上海医药工业研究院 | Silymarin behenic acid glyceride lipid nano particle oral solution dosage and its preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1771911A (en) | 2006-05-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhao et al. | Long-term storage of lipid-like nanoparticles for mRNA delivery | |
| Pardhi et al. | Nanocrystals: an overview of fabrication, characterization and therapeutic applications in drug delivery | |
| Vass et al. | Drying technology strategies for colon-targeted oral delivery of biopharmaceuticals | |
| Kumar et al. | Ketoconazole encapsulated in chitosan-gellan gum nanocomplexes exhibits prolonged antifungal activity | |
| Wang et al. | A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid–polymer hybrid nanoparticles | |
| Liu et al. | A mini review of nanosuspensions development | |
| Yu et al. | Dry powder aerosols of curcumin-chitosan nanoparticle complex prepared by spray freeze drying and their antimicrobial efficacy against common respiratory bacterial pathogens | |
| CN102274190B (en) | Paclitaxel alhumin submicron for injection and preparation method thereof | |
| CN103705469B (en) | A kind of honokiol nanoparticle and preparation method thereof | |
| Alfagih et al. | Pulmonary delivery of proteins using nanocomposite microcarriers | |
| He et al. | Formulating food protein-stabilized indomethacin nanosuspensions into pellets by fluid-bed coating technology: physical characterization, redispersibility, and dissolution | |
| CN103330680A (en) | Nano drug transdermal preparation and preparation method thereof | |
| CN104224710B (en) | A kind of docetaxel nanometer micella, its preparation method and application | |
| Alamdaran et al. | In-vitro study of the novel nanocarrier of chitosan-based nanoparticles conjugated HIV-1 P24 protein-derived peptides | |
| CN105456287A (en) | Selenium sulfide ultrafine powder and preparing method thereof | |
| Elsayed et al. | Inhalable nanocomposite microparticles: preparation, characterization and factors affecting formulation | |
| CN1771911B (en) | Re-dispersible nanometer particle of insoluble medicine and its preparation | |
| Tran et al. | Effects of storage on the stability and aerosolization efficiency of dry powder inhaler formulation of plasmid DNA-chitosan nanoparticles | |
| WO2018196819A1 (en) | Protein particle wrapped with medicine insoluble in water and preparation method therefor | |
| CN107137350A (en) | A kind of taxol polymer micelle and preparation method thereof | |
| Luo et al. | Targeted chemotherapy for breast cancer using an intelligent doxorubicin-loaded hexapeptide hydrogel | |
| CN108309943B (en) | Compound preparation based on medicine particles | |
| CN102018676B (en) | Method for preparing water-soluble medicine naonparticles and suspension aerosol thereof | |
| Ma et al. | Development and solidification of multifunction stabilizers formulated self-assembled core-shell Deacetyl mycoepoxydience nanosuspensions | |
| CN102133177B (en) | Plagiochin nanocrystal preparation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |