CN108478784A - A kind of pharmaceutical composition containing thymalfasin - Google Patents
A kind of pharmaceutical composition containing thymalfasin Download PDFInfo
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- CN108478784A CN108478784A CN201810511544.2A CN201810511544A CN108478784A CN 108478784 A CN108478784 A CN 108478784A CN 201810511544 A CN201810511544 A CN 201810511544A CN 108478784 A CN108478784 A CN 108478784A
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- thymalfasin
- pharmaceutical composition
- composition containing
- kettle
- solution
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
Abstract
The invention discloses a kind of pharmaceutical composition containing thymalfasin, described pharmaceutical composition includes that weight ratio is 1：13 thymalfasin and pharmaceutically acceptable high molecular material, by the way that ingredient to be dissolved in the mixed solvent of water/trifluoracetic acid/dichloromethane, crystalization in supercritical fluid precipitation is prepared.Pharmaceutical composition disclosed in this invention containing thymalfasin, it is with good stability, it can store for a long time at room temperature；And by selecting appropriate constituent, solvent and crystalization in supercritical fluid condition, the thymalfasin pharmaceutical composition with specific rate of release, grain size can be obtained, different medication demands can be met, there is larger application value.
Description
Technical field
The present invention relates to a kind of pharmaceutical compositions containing thymalfasin.
Background technology
Thymalfasin, also known as Thymine nucleotides (Thymosin- α 1) are immune regulators important in human body, can be used for
Treat chronic hepatitis B and enhancing immune system, while also have stimulation migration of vascular endothelial cells, promote angiogenesis and
Wound healing and other effects, have been used for hepatitis B, hepatitis C, malignant tumour and immune deficiency disorder etc. clinical treatment and
Research.Thymalfasin recognizes and receives for numerous doctors and patients as a kind of immunomodulator, clear mechanism.
The thymalfasin listed is freeze drying powder injection, such as the Zadaxin of import, domestic Ji Tai, Mai Puxin and day
Deng, thymalfasin is prepared into freeze drying powder injection by adding stabilizer, although its stability is made to obtain a degree of raising,
But 2-8 DEG C of storage is still needed to, and it is that the extremely complex physical chemistry occurred with caloic conversion becomes to be freeze-dried
Change process, many factors may influence the stability of finished product：Such as solution process for preparation it is possible that unstable quality, occurs
Degradation reaction；Surface action caused by high salt concentration caused by freezing concentration, pH value variation and dry dehydration in freeze-drying process；System
Agent moisture, auxiliary material crystallization etc..And the freeze drying powder injection administering mode listed is single, interval is short, and the duration is long, such as it
It is that every needle 1.6mg is subcutaneously injected in the recommended dose for the treatment of chronic hepatitis B, secondary weekly, successive administration 6 months (totally 52
Needle), during which it can not be interrupted, the compliance of such administering mode patient is very poor.
Invention content
It is good that the technical problem to be solved in the present invention is to provide a kind of stability, can be applied to prepare different modes of administration preparation
The pharmaceutical composition containing thymalfasin.
In order to solve the above technical problems, the invention discloses a kind of pharmaceutical composition containing thymalfasin, the composition
Including weight ratio is 1：The thymalfasin of 1-3 and pharmaceutically acceptable high molecular material, by the way that ingredient is dissolved in water/tri-
The mixed solvent of fluorine acetic acid/dichloromethane, crystalization in supercritical fluid precipitation are prepared.
The present invention is it was discovered by researchers that by being 1 by contained weight ratio：The thymalfasin of 1-3 and pharmaceutically acceptable
High molecular material is dissolved in the mixed solvent of water/trifluoracetic acid/dichloromethane, and what crystalization in supercritical fluid precipitation was prepared contains chest
The new pharmaceutical composition of gland method is with good stability, can store for a long time at room temperature.
When the high molecular material for being included is Macrogol 6000 or pluronic F-127, gained contains thymalfasin
Pharmaceutical composition have good dissolubility, add suitable hydroxypropyl methylcellulose can make pharmaceutical composition dispersibility more
Good, thymalfasin and the weight ratio of Macrogol 6000 or pluronic F-127 hydroxypropyl methylcelluloses are preferably 1：1.5：2.
When the high molecular material for being included is polylactic acid or Poly(D,L-lactide-co-glycolide, the method containing thymus gland of gained
New pharmaceutical composition can slow release, extension action time, reduction dosage rate, thymalfasin and polylactic acid or polylactic acid-
The weight ratio of co-glycolic acid is preferably 1：2.5.
The preparation method of pharmaceutical composition disclosed in this invention containing thymalfasin includes the following steps：A) mixed solution
Preparation：The mixed solvent of water/trifluoracetic acid/dichloromethane is added in the mixture of ingredient, is completely dissolved；b)CO2
Charging：Liquefy CO2By high-pressure pump through CO2Channel is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system, is passed through
Heating device and pressure-regulating valve regulation and control temperature in the kettle and pressure, make CO in kettle2Reach supercriticality；C) solution sample introduction：It is logical
The mixed solvent that solution channel is first passed through water/trifluoracetic acid/dichloromethane is crossed, after system reaches balance, mixed solvent is replaced
For the solution continuous sample introduction of step a) configuration, solvent is quickly and supercritical CO2It is sufficiently mixed and is flowed out through bottom and recycled, formation
Particles of solute falls to crystallization kettle bottom；D) dry：After sample introduction, continue to be passed through CO2To remove remaining solvent, then let out
Pressure collects sample in autoclave.
It is preferred that the volume ratio of mixed solvent water/trifluoracetic acid/dichloromethane is 4：2：4, the mass concentration of mixed solution is
30-50mg/mL, CO2Flow rate is 60mL/min, and pressure 160bar, 30 DEG C of temperature, the solution flow rate is 1.5mL/min, molten
Prefabricated nozzle diameter is 100 μm below liquid channel.
Pharmaceutical composition disclosed in this invention containing thymalfasin, it is with good stability, it can deposit for a long time at room temperature
It puts.And the disclosed pharmaceutical composition containing thymalfasin is prepared using crystalization in supercritical fluid precipitation, passes through selection
Appropriate constituent, solvent and crystalization in supercritical fluid condition, can obtain the thymalfasin with specific rate of release, grain size
Pharmaceutical composition, different medication demands can be met, there is larger application value.
Specific implementation mode
The above of the present invention is described in further detail again below by way of specific embodiment.But this should not be managed
Solution is limited only to embodiment below for the range of the above-mentioned theme of the present invention.The case where not departing from above-mentioned technological thought of the invention
Under, the various replacements or change made according to ordinary skill knowledge and customary means should all be included in the model of the present invention
In enclosing.
Embodiment 1
| Material forms | Prescription matches (g) |
| Thymalfasin | 1.0 |
| Macrogol 6000 | 1.0 |
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 50mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 3:3:4), make to be completely dissolved；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 30mL/min；
3) regulating and controlling temperature and pressure：It is 140bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 40 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured sprays into crystallization kettle by the intermediate channel of kettle head through 150 μm of nozzle
It is interior.Before being passed through solution, it is first passed through the mixed solvent (volume ratio 3 of water/trifluoracetic acid/dichloromethane:3:4) system, is made to reach flat
Weighing apparatus.The control of sample introduction flow rate is 1.3mL/min；
5) dry：After sample introduction, continue to be passed through CO220min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
Embodiment 2
| Material forms | Prescription matches (g) |
| Thymalfasin | 1.0 |
| Pluronic F-127 | 3.0 |
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 150mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 4:3:3), make to be completely dissolved；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 40mL/min；
3) regulating and controlling temperature and pressure：It is 150bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 35 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured is sprayed into through 80 μm of nozzle in crystallization kettle by the intermediate channel of kettle head.
Before being passed through solution, it is first passed through the mixed solvent (volume ratio 4 of water/trifluoracetic acid/dichloromethane:3:3) system, is made to reach balance.
The control of sample introduction flow rate is 1.4mL/min；
5) dry：After sample introduction, continue to be passed through CO215min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
Embodiment 3
Prescription：
| Material forms | Prescription matches (g) |
| Thymalfasin | 1.0 |
| Pluronic F-127 | 1.5 |
| Hydroxypropyl methylcellulose | 2.0 |
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 140mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 4:2:4), make to be completely dissolved；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 60mL/min；
3) regulating and controlling temperature and pressure：It is 160bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 30 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured sprays into crystallization kettle by the intermediate channel of kettle head through 100 μm of nozzle
It is interior.Before being passed through solution, it is first passed through the mixed solvent (volume ratio 4 of water/trifluoracetic acid/dichloromethane:2:4) system, is made to reach flat
Weighing apparatus.The control of sample introduction flow rate is 1.5mL/min；
5) dry：After sample introduction, continue to be passed through CO220min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
Embodiment 4
Prescription：
| Material forms | Prescription matches (g) |
| Thymalfasin | 1.0 |
| Macrogol 6000 | 2.5 |
| Hydroxypropyl methylcellulose | 2.0 |
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 150mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 4:2:4), make to be completely dissolved；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 60mL/min；
3) regulating and controlling temperature and pressure：It is 160bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 30 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured is sprayed into through 80 μm of nozzle in crystallization kettle by the intermediate channel of kettle head.
Before being passed through solution, it is first passed through the mixed solvent (volume ratio 4 of water/trifluoracetic acid/dichloromethane:2:4) system, is made to reach balance.
The control of sample introduction flow rate is 1.5mL/min；
5) dry：After sample introduction, continue to be passed through CO220min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
Embodiment 5
Prescription：
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 140mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 4:2:4), make to be completely dissolved, L-AA/L-AA sodium is added and is adjusted to pH value 6.5；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 60mL/min；
3) regulating and controlling temperature and pressure：It is 160bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 30 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured sprays into crystallization kettle by the intermediate channel of kettle head through 100 μm of nozzle
It is interior.Before being passed through solution, it is first passed through the mixed solvent (volume ratio 4 of water/trifluoracetic acid/dichloromethane:2:4) system, is made to reach flat
Weighing apparatus.The control of sample introduction flow rate is 1.5mL/min；
5) dry：After sample introduction, continue to be passed through CO220min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
Embodiment 6
Prescription：
| Material forms | Prescription matches (g) |
| Thymalfasin | 1.0 |
| Polylactic acid | 1.0 |
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 45mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 4:2:4), make to be completely dissolved；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 60mL/min；
3) regulating and controlling temperature and pressure：It is 160bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 30 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured is sprayed into through 10 μm of nozzle in crystallization kettle by the intermediate channel of kettle head.
Before being passed through solution, it is first passed through the mixed solvent (volume ratio 4 of water/trifluoracetic acid/dichloromethane:2:4) system, is made to reach balance.
The control of sample introduction flow rate is 1.5mL/min；
5) dry：After sample introduction, continue to be passed through CO220min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
Embodiment 7
Prescription：
| Material forms | Prescription matches (g) |
| Thymalfasin | 1.0 |
| Poly(D,L-lactide-co-glycolide | 2.5 |
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 50mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 4:2:4), make to be completely dissolved；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 60mL/min；
3) regulating and controlling temperature and pressure：It is 160bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 30 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured is sprayed into through 10 μm of nozzle in crystallization kettle by the intermediate channel of kettle head.
Before being passed through solution, it is first passed through the mixed solvent (volume ratio 4 of water/trifluoracetic acid/dichloromethane:2:4) system, is made to reach balance.
The control of sample introduction flow rate is 1.5mL/min；
5) dry：After sample introduction, continue to be passed through CO220min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
Embodiment 8
Prescription：
| Material forms | Prescription matches (g) |
| Thymalfasin | 1.0 |
| Poly(D,L-lactide-co-glycolide | 2.5 |
| L-AA/L-AA sodium | In right amount |
Preparation method：
1) preparation of mixed solution：Each material is accurately weighed, the mixing that 50mL water/trifluoracetic acid/dichloromethane is added is molten
Agent (volume ratio 4:2:4), make to be completely dissolved, L-AA/L-AA sodium is added and is adjusted to pH value 6.5；
2) liquefy CO2It is continually introduced into the high pressure crystal kettle of crystalization in supercritical fluid equipment system through high-pressure pump, control stream
Fast 60mL/min；
3) regulating and controlling temperature and pressure：It is 160bar to control pressure in high pressure crystal kettle, and passes through preheater and insulating box control
Temperature in the kettle processed is 30 DEG C, makes CO in kettle2Reach supercriticality；
4) solution sample introduction：The solution that step 1 is configured sprays into crystallization kettle by the intermediate channel of kettle head through 100 μm of nozzle
It is interior.Before being passed through solution, it is first passed through the mixed solvent (volume ratio 4 of water/trifluoracetic acid/dichloromethane:2:4) system, is made to reach flat
Weighing apparatus.The control of sample introduction flow rate is 1.5mL/min；
5) dry：After sample introduction, continue to be passed through CO220min is to remove remaining solvent；
6) sample in autoclave is collected in pressure release.
The experimental test result of the pharmaceutical composition containing thymalfasin prepared by above example of the present invention is as follows：
1) electron microscope scanning result is shown：Sample prepared by the embodiment of the present invention is fluffy white powder,
Sample dispersion is uniform, and primitive is the microballoon of a diameter of micro/nano level, and size is uniform, and no bulk crystals add water soluble or mixing.
Concrete outcome see the table below 1：
Table 1
| Character | Clarity of solution and color | Grain size (μm) | |
| Embodiment 1 | Fluffy white powder | Clear, colorless | 1.3 |
| Embodiment 2 | Fluffy white powder | Clear, colorless | 0.8 |
| Embodiment 3 | Fluffy white powder | Clear, colorless | 0.9 |
| Embodiment 4 | Fluffy white powder | Clear, colorless | 0.8 |
| Embodiment 5 | Fluffy white powder | Clear, colorless | 1.0 |
| Embodiment 6 | Fluffy white powder | Clear, colorless | 0.07 |
| Embodiment 7 | Fluffy white powder | Clear, colorless | 0.06 |
| Embodiment 8 | Fluffy white powder | Clear, colorless | 1.0 |
2) pharmacokinetics of evaluation embodiment of the present invention sample (or preparation of its preparation), as a result shows the present invention
Embodiment sample (or preparation of its preparation) has clinical advantage：Or easy to use or bioavilability is high, or with apparent slow
Effect is released, action time is longer, and concrete outcome see the table below 2.Evaluation method：The thymalfasin preparation that rat has listed is given respectively
(Zadaxin, reference preparation) and sample of the embodiment of the present invention (or preparation of its preparation), evaluate relative bioavailability and blood medicine
Concentration is less than the time of quantitative limit.
Table 2
3) pharmaceutical composition containing thymalfasin prepared by embodiment places under the conditions of 25 DEG C of 60%RH and investigates it surely
Qualitative, the stability of Examples 1 to 8 is all preferable.Concrete outcome see the table below 3：
Table 3
Claims (10)
1. a kind of pharmaceutical composition containing thymalfasin, is characterized in that：The composition includes that weight ratio is 1：The thymus gland method of 1-3
New and pharmaceutically acceptable high molecular material, it is molten by the mixing that ingredient is dissolved in water/trifluoracetic acid/dichloromethane
Agent, crystalization in supercritical fluid precipitation are prepared.
2. the pharmaceutical composition containing thymalfasin as described in claim 1, is characterized in that：The high molecular material is poly- second two
Alcohol 6000 or pluronic F-127.
3. the pharmaceutical composition containing thymalfasin as claimed in claim 2, is characterized in that：The composition also includes hydroxypropyl first
Cellulose.
4. the pharmaceutical composition containing thymalfasin as claimed in claim 3, is characterized in that：Thymalfasin and poly- in the ingredient
The weight ratio of ethylene glycol 6000 or pluronic F-127 hydroxypropyl methylcelluloses is 1：1.5：2.
5. the pharmaceutical composition containing thymalfasin as described in claim 1, is characterized in that：The high molecular material is polylactic acid
Or Poly(D,L-lactide-co-glycolide.
6. the pharmaceutical composition containing thymalfasin as claimed in claim 5, is characterized in that：Thymalfasin and poly- in the ingredient
The weight ratio of lactic acid or Poly(D,L-lactide-co-glycolide is 1：2.5.
7. the pharmaceutical composition containing thymalfasin as described in any one of claim 3-6, is characterized in that：The composition is also
Including L-AA sodium.
8. the preparation method of the pharmaceutical composition containing thymalfasin as described in claim 1, is characterized in that：Its preparation process packet
Include following steps：
A) preparation of mixed solution：The mixed solvent of water/trifluoracetic acid/dichloromethane is added in the mixture of ingredient,
It is completely dissolved；
b)CO2Charging：Liquefaction CO2 is by high-pressure pump through CO2Channel is continually introduced into the high pressure crystal of crystalization in supercritical fluid equipment system
In kettle, temperature in the kettle and pressure are regulated and controled by heating device and pressure-regulating valve, make CO in kettle2Reach supercriticality；
C) solution sample introduction：The mixed solvent of water/trifluoracetic acid/dichloromethane is first passed through by solution channel, system reaches balance
Afterwards, mixed solvent is changed to the solution continuous sample introduction of step a) configuration, solvent is quickly and supercritical CO2It is sufficiently mixed and through kettle
Bottom outflow recycling, the particles of solute of formation fall to crystallization kettle bottom；
D) dry：After sample introduction, continue to be passed through CO2 to remove remaining solvent, sample in autoclave is collected in subsequent pressure release.
9. the preparation method of the pharmaceutical composition containing thymalfasin as claimed in claim 8, is characterized in that：The mixed solvent
The volume ratio of water/trifluoracetic acid/dichloromethane is 4：2：4, the mass concentration of mixed solution is 30-50mg/mL, the CO2Stream
Rate is 60mL/min, and pressure is 16M bar, and 30 DEG C of temperature, the solution flow rate is 1.5mL/min, and solution channel lower section is prefabricated
Nozzle diameter is 100 μm.
10. the purposes of the pharmaceutical composition containing thymalfasin as described in claim 1, is characterized in that：For filling capsule, system
Standby dry suspensoid agent, Foradil Aerolizer formoterol fumarate or packing injection.
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| CN201810511544.2A CN108478784B (en) | 2018-05-25 | 2018-05-25 | A kind of pharmaceutical composition containing thymalfasin |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1720902A (en) * | 2005-06-23 | 2006-01-18 | 同济大学 | The supercritical anti-dissolving agent process prepares the method for biological degradable polymer drug-carried fine particle |
| CN105753962A (en) * | 2016-03-09 | 2016-07-13 | 海南正瑞医药科技开发有限公司 | Thymalfasin crystal and pharmaceutical composition thereof |
-
2018
- 2018-05-25 CN CN201810511544.2A patent/CN108478784B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1720902A (en) * | 2005-06-23 | 2006-01-18 | 同济大学 | The supercritical anti-dissolving agent process prepares the method for biological degradable polymer drug-carried fine particle |
| CN105753962A (en) * | 2016-03-09 | 2016-07-13 | 海南正瑞医药科技开发有限公司 | Thymalfasin crystal and pharmaceutical composition thereof |
Non-Patent Citations (1)
| Title |
|---|
| 高静: "胸腺五肽肺部吸入粉雾剂的研制及其药效学研究", 《中国优秀博硕士学位论文全文数据库（博士） 医药卫生科技辑》 * |
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