CN104491848A - Anti-AIDS nano-microsphere - Google Patents
Anti-AIDS nano-microsphere Download PDFInfo
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- CN104491848A CN104491848A CN201410767852.3A CN201410767852A CN104491848A CN 104491848 A CN104491848 A CN 104491848A CN 201410767852 A CN201410767852 A CN 201410767852A CN 104491848 A CN104491848 A CN 104491848A
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Abstract
The invention discloses an anti-AIDS nano-microsphere. The nano-microsphere comprises AIDS virus lysozyme, nano-particles, polymer and medicinal auxiliaries. The preparation method comprises the following steps: preparing a nano-drug from the AIDS virus lysozyme and medicinal auxiliaries; adding the nano-drug into an organic solvent mixed solution containing polymer for emulsifying to prepare a nano-drug suspension; adding the nano-drug suspension into the nano-particles for re-emulsifying to obtain a nano-particle suspension; solidifying the nano-particle suspension, and centrifuging to collect the microsphere. According to the invention, proper polymer materials and the microsphere preparation method are selected, the prepared microsphere has the characteristics of high drug-loading capacity and high encapsulation efficiency, and has an effect of reinforcing cell adhesion since a nano-particle layer is assembled on the surface of the microsphere, so that the absorption rate of an AIDS patient to the AIDS virus lysozyme can be greatly improved.
Description
[technical field]
The present invention relates to Nano medication granule, specifically, be a kind of anti-AIDS nanometer microsphere, belong to pharmaceutical technology sectors.
[technical background]
Acquired immune deficiency syndrome (AIDS) is a kind of disease of the compromised immune caused because of viral infection, and the untoward reaction of HIV sufferers is relevant to the selection of antiviral therapy scheme, and the most untoward reaction of HIV sufferers betides in 1st month after treatment.After antiviral therapy, Most patients CD4+T cell counting rises all to some extent.At present still without radical cure measure, but the life cycle of patient effectively can be extended by antiviral therapy, improve the life quality of patient, but long-term antiviral therapy can cause the many untoward reaction of patient, as common symptom of digestive tract, neuromuscular system untoward reaction, and more serious hepatic and renal function is impaired, bone marrow depression etc., once occur that untoward reaction produces certain impact by the compliance of the patient implementing antiviral therapy.
Nano medication of the present invention can improve the drug level near HIV sufferers sick cell thus improves the utilization rate of medicine and reduce medicine normal tissue organ toxic and side effects.And anti-AIDS nanometer medicine microspheres provided by the invention, the utilization rate of medicine can not only be improved and reduce medicine normal tissue organ toxic and side effects, and have selected suitable polymeric material and method for preparing microsphere, high and the feature that envelop rate is high of microsphere drug loading of preparation, and its surface-assembled one deck nano-particle has the effect of enhancing cell adhesion, greatly improve human body to AIDS virus lytic enzyme absorbance.
[summary of the invention]
In order to effectively acquired immune deficiency syndrome (AIDS) can be treated, alleviate the misery of HIV sufferers, the invention provides a kind of anti-AIDS nanometer microsphere, and anti-AIDS nanometer medicine microspheres provided by the invention, the interest rate of medicine can not only be improved and reduce medicine normal tissue organ toxic and side effects, and have selected suitable polymeric material and method for preparing microsphere, high and the feature that envelop rate is high of microsphere drug loading of preparation, and its surface-assembled one deck nano-particle has the effect of enhancing cell adhesion, greatly improve human body to AIDS virus lytic enzyme absorbance.
The invention provides following technical scheme:
A kind of anti-AIDS nanometer microsphere, adopts following technical scheme to obtain:
A, AIDS virus lytic enzyme and pharmaceutic adjuvant are prepared into Nano medication, in described Nano medication, the percentage by weight of AIDS virus lytic enzyme is 0.10%-45%, and the percentage by weight of pharmaceutic adjuvant is 0.01%-30%;
It is carry out emulsifying in the organic solvent mixed liquor of 50%-15.0% polymer to obtain Nano medication suspension that B, Nano medication step (1) prepared are dispersed in weight percent concentration according to the weight ratio of 1:1-1:10;
C, emulsifying in step (2) to be obtained Nano medication suspension joins containing percentage by weight be carry out in the suspension of 5%-55% nano-particle double emulsionly obtaining nano-particle suspension;
D, to transfer to obtained nano-particle suspension double emulsion in step (3) containing percentage by weight be solidify 5-10 hour in the aqueous solution of 1%-5% inorganic salts;
E, sample obtained in step (4) is carried out centrifugalize, collect microsphere, and wash thus obtained microsphere, lyophilizing afterwards, obtaining surface self-organization has nano-particle and the inner microsphere containing AIDS virus lytic enzyme.
A kind of anti-AIDS nanometer microsphere, in the process adopting as above technical scheme to prepare, note following some:
In a, above-described anti-AIDS nanometer method for preparing microsphere, pharmaceutic adjuvant described in steps A is injecting drug use adjuvant, the one in the optional little saccharide of medication adjuvant (as sucrose, trehalose, glucose, maltose or lactose etc.), polyhydroxy compounds (as glucosan, sodium alginate, chitosan, starch, cellulose or cyclodextrin etc.), amino-acid compound (as lysine, arginine, glutamic acid or histidine etc.) or inorganic salts material (as mantoquita, calcium salt, magnesium salt, molybdenum salt etc.) or combination in any.
In b, above-described anti-AIDS nanometer method for preparing microsphere, the polymer in step B selects one or more in caprolactone, polylactic acid, polylactic acid-polyglycol, poly lactic-co-glycolic acid, hydroxyacetic acid-polylactic acid-polyglycol or polyethylene glycol-caprolactone.
In c, above-described anti-AIDS nanometer method for preparing microsphere, in step B, in polymer organic solvent mixed solution, also should be added with the Polyethylene Glycol that percentage by weight is 1%-15% or poloxamer.
In d, above-described anti-AIDS nanometer method for preparing microsphere, the organic solvent in step B in polymer organic solvent mixed solution is selected from one or more in ethyl acetate, acetonitrile, chloroform, dichloromethane or acetone.
In e, above-described anti-AIDS nanometer method for preparing microsphere, in step D, inorganic salts can be selected from one in mantoquita, calcium salt, magnesium salt, molybdenum salt etc. or combination in any.
The present invention adopts above technical scheme to prepare, have selected suitable polymeric material and method for preparing microsphere, high and the feature that envelop rate is high of microsphere drug loading of preparation, and its surface-assembled one deck nano-particle has the effect of enhancing cell adhesion, greatly improve human body to AIDS virus lytic enzyme absorbance.
[detailed description of the invention]
Below in conjunction with specific embodiment, the present invention is elaborated.But should be appreciated that, these embodiments only for illustration of the present invention, and are not intended to limit the scope of the invention.The improvement made according to the present invention of those skilled in the art and adjustment, still belong to protection scope of the present invention in actual applications.
Embodiment 1
Be loaded with the preparation method of AIDS virus lytic enzyme Nano microsphere, comprise the steps:
(1) getting 10mg AIDS virus lytic enzyme is dissolved in pharmaceutic adjuvant, then pharmaceutic adjuvant is added--little saccharide is (as sucrose, trehalose, glucose, maltose or lactose etc.), choose the pharmaceutic adjuvant of sucrose as this embodiment, 10mg AIDS virus lytic enzyme is dissolved in 0.5mg sucrose, then above-mentioned solution being transferred to 3.0ml concentration is in Polyethylene Glycol (PEG8000) aqueous solution of 3%, abundant mixing, then-80 DEG C of refrigerator pre-freezes 10 hours, use freeze dryer lyophilizing again, then wash with dichloromethane and dissolve PEG centrifugal removing PEG obtains anti-AIDS nanometer medicine,
(2) Nano medication obtained in step one being dosed weight percent concentration is 6.0% have in the organic solvent of polymer to exchange and be prepared into nano-particle suspended emulsion, chooses caprolactone and the polylactic acid organic solvent as polymer;
(3) emulsifying in step (2) being obtained that Nano medication suspension joins containing percentage by weight is carry out in the suspension of 15.0% nano-particle double emulsionly obtaining nano-particle suspension;
(4) being transferred to by obtained nano-particle suspension double emulsion in step (3) containing percentage by weight is solidify 6 hours in the aqueous solution of 1.5% inorganic salts;
(5) sample obtained in step (4) is carried out centrifugalize, collect microsphere, and wash thus obtained microsphere, lyophilizing afterwards, obtaining surface self-organization has nano-particle and the inner microsphere containing AIDS virus lytic enzyme.
AIDS virus lytic enzyme Nano microsphere obtained in the present embodiment, the percentage by weight of medicine is 39.2%, and the percentage by weight of polymer is 39.0%, and the percentage by weight of pharmaceutic adjuvant is 21.8%.
Embodiment 2
Be loaded with the preparation method of AIDS virus lytic enzyme Nano microsphere, comprise the steps:
(1) getting 10mg AIDS virus lytic enzyme is dissolved in pharmaceutic adjuvant, then pharmaceutic adjuvant is added--little saccharide is (as sucrose, trehalose, glucose, maltose or lactose etc.), choose the pharmaceutic adjuvant of maltose as this embodiment, 10mg AIDS virus lytic enzyme is dissolved in 0.5mg maltose, then above-mentioned solution being transferred to 3.0ml concentration is in Polyethylene Glycol (PEG8000) aqueous solution of 3%, abundant mixing, then-80 DEG C of refrigerator pre-freezes 10 hours, use freeze dryer lyophilizing again, then wash with dichloromethane and dissolve PEG centrifugal removing PEG obtains anti-AIDS nanometer medicine,
(2) Nano medication obtained in step one being dosed weight percent concentration is 7.5% have in the organic solvent of polymer to exchange and be prepared into nano-particle suspended emulsion, chooses the organic solvent of polylactic acid-polyglycol as polymer;
(3) emulsifying in step (2) being obtained that Nano medication suspension joins containing percentage by weight is carry out in the suspension of 16.5% nano-particle double emulsionly obtaining nano-particle suspension;
(4) being transferred to by obtained nano-particle suspension double emulsion in step (3) containing percentage by weight is solidify 7 hours in the aqueous solution of 2.5% inorganic salts;
(5) sample obtained in step (4) is carried out centrifugalize, collect microsphere, and wash thus obtained microsphere, lyophilizing afterwards, obtaining surface self-organization has nano-particle and the inner microsphere containing AIDS virus lytic enzyme.
AIDS virus lytic enzyme Nano microsphere obtained in the present embodiment, the percentage by weight of medicine is 40.6%, and the percentage by weight of polymer is 38.5%, and the percentage by weight of pharmaceutic adjuvant is 20.9%.
Embodiment 3
Be loaded with the preparation method of AIDS virus lytic enzyme Nano microsphere, comprise the steps:
(1), getting 15mg AIDS virus lytic enzyme is dissolved in pharmaceutic adjuvant, then pharmaceutic adjuvant is added--polyhydroxy compounds is (as glucosan, sodium alginate, chitosan, starch, cellulose or cyclodextrin etc.), choose the pharmaceutic adjuvant of sodium alginate as this embodiment, 15mg AIDS virus lytic enzyme is dissolved in 0.2mg sodium alginate, then above-mentioned solution being transferred to 3.0ml concentration is in Polyethylene Glycol (PEG8000) aqueous solution of 3%, abundant mixing, then-80 DEG C of refrigerator pre-freezes 10 hours, use freeze dryer lyophilizing again, then wash with dichloromethane and dissolve PEG centrifugal removing PEG obtains anti-AIDS nanometer medicine,
(2) Nano medication obtained in step one being dosed weight percent concentration is 8.5% have in the organic solvent of polymer to exchange and be prepared into nano-particle suspended emulsion, chooses caprolactone and the polylactic acid organic solvent as polymer;
(3) emulsifying in step (2) being obtained that Nano medication suspension joins containing percentage by weight is carry out in the suspension of 17.0% nano-particle double emulsionly obtaining nano-particle suspension;
(4) being transferred to by obtained nano-particle suspension double emulsion in step (3) containing percentage by weight is solidify 6.5 hours in the aqueous solution of 3.5% inorganic salts;
(5) sample obtained in step (4) is carried out centrifugalize, collect microsphere, and wash thus obtained microsphere, lyophilizing afterwards, obtaining surface self-organization has nano-particle and the inner microsphere containing AIDS virus lytic enzyme.
AIDS virus lytic enzyme Nano microsphere obtained in the present embodiment, the percentage by weight of medicine is 42.2%, and the percentage by weight of polymer is 39.5%, and the percentage by weight of pharmaceutic adjuvant is 18.3%.
Embodiment 4
Be loaded with the preparation method of AIDS virus lytic enzyme Nano microsphere, comprise the steps:
(1), getting 20mg AIDS virus lytic enzyme is dissolved in pharmaceutic adjuvant, then pharmaceutic adjuvant is added--polyhydroxy compounds is (as glucosan, sodium alginate, chitosan, starch, cellulose or cyclodextrin etc.), choose cellulose and the cyclodextrin pharmaceutic adjuvant as this embodiment, 20mg AIDS virus lytic enzyme is dissolved in 0.3mg cellulose and cyclodextrin, then above-mentioned solution being transferred to 3.0ml concentration is in Polyethylene Glycol (PEG8000) aqueous solution of 3%, abundant mixing, then-80 DEG C of refrigerator pre-freezes 10 hours, use freeze dryer lyophilizing again, then wash with dichloromethane and dissolve PEG centrifugal removing PEG obtains anti-AIDS nanometer medicine,
(2) Nano medication obtained in step one being dosed weight percent concentration is 9.0% have in the organic solvent of polymer to exchange and be prepared into nano-particle suspended emulsion, chooses polylactic acid-polyglycol and the poly lactic-co-glycolic acid organic solvent as polymer;
(3) emulsifying in step (2) being obtained that Nano medication suspension joins containing percentage by weight is carry out in the suspension of 17.5% nano-particle double emulsionly obtaining nano-particle suspension;
(4) being transferred to by obtained nano-particle suspension double emulsion in step (3) containing percentage by weight is solidify 6.5 hours in the aqueous solution of 3.5% inorganic salts;
(5) sample obtained in step (4) is carried out centrifugalize, collect microsphere, and wash thus obtained microsphere, lyophilizing afterwards, obtaining surface self-organization has nano-particle and the inner microsphere containing AIDS virus lytic enzyme.
AIDS virus lytic enzyme Nano microsphere obtained in the present embodiment, the percentage by weight of medicine is 41.8%, and the percentage by weight of polymer is 40.5%, and the percentage by weight of pharmaceutic adjuvant is 17.7%.
Embodiment 5
Be loaded with the preparation method of AIDS virus lytic enzyme Nano microsphere, comprise the steps:
(1), getting 20mg AIDS virus lytic enzyme is dissolved in pharmaceutic adjuvant, then pharmaceutic adjuvant is added--amino-acid compound is (as lysine, arginine, glutamic acid or histidine etc.), choose the pharmaceutic adjuvant of glutamic acid as this embodiment, 20mg AIDS virus lytic enzyme is dissolved in 0.3mg glutamic acid, then above-mentioned solution being transferred to 3.0ml concentration is in Polyethylene Glycol (PEG8000) aqueous solution of 3%, abundant mixing, then-80 DEG C of refrigerator pre-freezes 10 hours, use freeze dryer lyophilizing again, then wash with dichloromethane and dissolve PEG centrifugal removing PEG obtains anti-AIDS nanometer medicine,
(2) Nano medication obtained in step one being dosed weight percent concentration is 8.30% have in the organic solvent of polymer to exchange and be prepared into nano-particle suspended emulsion, chooses polylactic acid-polyglycol and the poly lactic-co-glycolic acid organic solvent as polymer;
(3) emulsifying in step (2) being obtained that Nano medication suspension joins containing percentage by weight is carry out in the suspension of 16.5% nano-particle double emulsionly obtaining nano-particle suspension;
(4) being transferred to by obtained nano-particle suspension double emulsion in step (3) containing percentage by weight is solidify 7 hours in the aqueous solution of 4.5% inorganic salts;
(5) sample obtained in step (4) is carried out centrifugalize, collect microsphere, and wash thus obtained microsphere, lyophilizing afterwards, obtaining surface self-organization has nano-particle and the inner microsphere containing AIDS virus lytic enzyme.
AIDS virus lytic enzyme Nano microsphere obtained in the present embodiment, the percentage by weight of medicine is 42.6%, and the percentage by weight of polymer is 39.6%, and the percentage by weight of pharmaceutic adjuvant is 17.8%.
Although the present invention is described in detail above to have used general explanation and specific embodiment, and on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Claims (8)
1. an anti-AIDS nanometer microsphere; it is characterized in that; described anti-AIDS nanometer microsphere is prepared by the following method; AIDS virus lytic enzyme and pharmaceutic adjuvant are prepared into Nano medication; described Nano medication is added in the organic solvent mixed liquor containing polymer and carry out emulsifying, obtained Nano medication suspension, then Nano medication suspension is added in nano-particle carry out double emulsionly obtaining nano-particle suspension; again nano-particle suspension is cured, collected by centrifugation microsphere.
2. an anti-AIDS nanometer microsphere, is characterized in that, described AIDS virus lytic enzyme is the serum preparation directly or indirectly extracted from mosquito body.
3. anti-AIDS nanometer microsphere according to claim 1, it is characterized in that, in Nano microsphere, the percentage by weight of AIDS virus lytic enzyme is 0.10%-45%, and the percentage by weight of pharmaceutic adjuvant is 0.01%-30%, and the percentage by weight of polymer is 3.50%-55.0%.
4. anti-AIDS nanometer microsphere according to claim 1, is characterized in that, comprise the following steps:
(1) AIDS virus lytic enzyme and pharmaceutic adjuvant are prepared into Nano medication, in described Nano medication, the percentage by weight of AIDS virus lytic enzyme is 0.10%-45%, and the percentage by weight of pharmaceutic adjuvant is 0.01%-30%;
(2) it is carry out emulsifying in the organic solvent mixed liquor of 5.0%-15.0% polymer to obtain Nano medication suspension that Nano medication step (1) prepared is dispersed in weight percent concentration according to the weight ratio of 1:1-1:10;
(3) emulsifying in step (2) being obtained that Nano medication suspension joins containing percentage by weight is carry out in the suspension of 5%-55% nano-particle double emulsionly obtaining nano-particle suspension;
(4) transferring to obtained nano-particle suspension double emulsion in step (3) containing percentage by weight is solidify 5-10 hour in the aqueous solution of 1%-5% inorganic salts;
(5) sample obtained in step (4) is carried out centrifugalize, collect microsphere, and wash thus obtained microsphere, lyophilizing afterwards, obtaining surface self-organization has nano-particle and the inner microsphere containing anti-AIDS drug.
5. the anti-AIDS nanometer microsphere according to claim 1,2,3, it is characterized in that, in step as above (1), pharmaceutic adjuvant is injecting drug use adjuvant, the optional polysaccharide compound of medication adjuvant, amino-acid compound, inorganic salts material, little saccharide or polyhydroxy compounds, one or more in waiting.
6. the anti-AIDS nanometer microsphere according to claim 1,2,3, it is characterized in that, the polymer in step as above (2) selects one or more in caprolactone, polylactic acid, polylactic acid-polyglycol, poly lactic-co-glycolic acid, hydroxyacetic acid-polylactic acid-polyglycol or polyethylene glycol-caprolactone.
7. the anti-AIDS nanometer microsphere according to claim 1,2,3, is characterized in that, also should be added with the Polyethylene Glycol or poloxamer that percentage by weight is 1%-15% in step as above (2) in polymer organic solvent mixed solution.
8. the anti-AIDS nanometer microsphere according to claim 1,2,3, it is characterized in that, the organic solvent in step as above (2) in polymer organic solvent mixed solution is selected from one or more in ethyl acetate, acetonitrile, chloroform, dichloromethane or acetone.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101869579A (en) * | 2009-04-23 | 2010-10-27 | 罗家弃 | AIDS virus lytic enzyme |
| CN203315381U (en) * | 2012-10-22 | 2013-12-04 | 唐伟钊 | Nanometer anti-AIDS (Acquired Immune Deficiency Syndrome) and anti-inflammatory medicament with radiotherapy function |
| CN103690491A (en) * | 2013-10-14 | 2014-04-02 | 皖南医学院 | Preparation method of PEG-PLA/PLA composite drug loaded nanometer microballoon |
| CN103768621A (en) * | 2012-10-22 | 2014-05-07 | 唐伟钊 | Nano targeted or conventional anti-AIDS or anti-inflammatory-infection medicine with radiotherapy function and preparation method thereof |
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2014
- 2014-12-12 CN CN201410767852.3A patent/CN104491848A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101869579A (en) * | 2009-04-23 | 2010-10-27 | 罗家弃 | AIDS virus lytic enzyme |
| CN203315381U (en) * | 2012-10-22 | 2013-12-04 | 唐伟钊 | Nanometer anti-AIDS (Acquired Immune Deficiency Syndrome) and anti-inflammatory medicament with radiotherapy function |
| CN103768621A (en) * | 2012-10-22 | 2014-05-07 | 唐伟钊 | Nano targeted or conventional anti-AIDS or anti-inflammatory-infection medicine with radiotherapy function and preparation method thereof |
| CN103690491A (en) * | 2013-10-14 | 2014-04-02 | 皖南医学院 | Preparation method of PEG-PLA/PLA composite drug loaded nanometer microballoon |
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Application publication date: 20150408 |