CN106309370A - Paclitaxel pH-sensitive long-circulation liposome and preparation method thereof - Google Patents
Paclitaxel pH-sensitive long-circulation liposome and preparation method thereof Download PDFInfo
- Publication number
- CN106309370A CN106309370A CN201610835887.5A CN201610835887A CN106309370A CN 106309370 A CN106309370 A CN 106309370A CN 201610835887 A CN201610835887 A CN 201610835887A CN 106309370 A CN106309370 A CN 106309370A
- Authority
- CN
- China
- Prior art keywords
- paclitaxel
- long circulating
- circulating liposomes
- quick
- liposome
- 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.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a paclitaxel pH-sensitive long-circulation liposome. The paclitaxel pH-sensitive long-circulation liposome is characterized by being prepared from the following matters in percentages by mass: 0.5-3% of paclitaxel, 1-10% of hemisuccinate cholesterol, 5-15% of a pH-sensitive film material, 0.1-1% of a hydrophilic material and 75-90% of a hydration medium material. By the liposome provided by the invention, the shortcoming that the paclitaxel is not water-soluble is overcome. Compared with an existing preparation, the paclitaxel pH-sensitive long-circulation liposome has the characteristics that toxic and side effects are reduced, due to long acting time of the liposome, drug administration time is prolonged, compliance of a patient is increased, meanwhile, targeting ability of the paclitaxel as a chemotherapy drug is improved, and the anti-tumor effect is improved.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular it relates to the quick long circulating liposomes of the pH of antitumor drug paclitaxel
And preparation method thereof.
Background technology
Paclitaxel is a complicated diterpene-kind compound, and by suppressing micro-pipe to realize antitumor action, it is one
Outstanding broad-spectrum anti-cancer drug.Paclitaxel can produce bone marrow depression, peripheral nervous toxicity, muscle/arthralgia, arrhythmia
And the toxic and side effects such as gastrointestinal toxicity, its dose limiting toxicity reduces for biting neutrophilic leukocyte.Owing to paclitaxel is in water
Solvability is very poor, so commercially available preparation uses Cremophor EL and ethanol as solvent.Cremophor EL can cause
Serious anaphylaxis, even if using 17-hydroxy-11-dehydrocorticosterone and antihistamine drug in advance, the incidence rate of this untoward reaction is still 41%
Left and right.And the use of Cremophor El so that paclitaxel is in vivo in nonlinear kinetics.
Avoid the use of Cremophor EL, reduce the toxic and side effects of medicine, paclitaxel is made Liposomal formulation
One important purpose.Such as, the Paclitaxel liposome preparation of company of the U.S., trade name LEP-ETU.This prescription includes
DOPC, cholesterol and cuorin (mol ratio is 90:5:5), wherein the concentration of paclitaxel is the mol ratio of 2mg/ml, medicine and fat
For 1:33, the mean diameter of liposome is 150nm.The clinical trial of this liposome shows that the maximum tolerated dose of LEP-ETU surpasses
Crossing commercial preparation Taxol, even if not accepting antihistamine drug treatment, Most patients is also resistant to repeatedly infuse.
The vesicle that lipid system is film material by phospholipid and additives form, has bilayer structure.Owing to it is tied
Structure is similar to biomembrane, can encapsulate water solublity and fat-soluble medicine, has raising medicine stability, less drug dose, reduces poison
Property；Change the advantage such as medicine distribution in vivo energy targeting release and extensively noted and and further investigation.
In recent years, research and the application of liposome have remarkable progress, and the liposome of some medicines has been used for multiple administration on the way
Footpath and preparation have also carried out clinical practice widely.As pharmaceutical carrier, liposome can be used for tumor, infectious disease, painstaking effort
The treatment of pipe disease and dermatosis etc..
So, find that the poor stability of liposome has become the subject matter in its application simultaneously, after liposome enters human body,
Due to various factors effects such as the haemproteins in blood, opsonin, antibody, liposome ruptures, the quick seepage of encapsulation object medicine,
Quickly by reticuloendothelial system identification, absorption, limit its target function.
Summary of the invention
It is contemplated that overcome drawbacks described above, solve paclitaxel water-insoluble and the problem of side effect, thus allow and be prepared for
A kind of quick long circulating liposomes of paclitaxel pH and preparation method thereof.
A kind of quick long circulating liposomes of paclitaxel pH that the present invention provides, it is characterised in that contained by following mass percent
The material of amount is prepared from:
Further, a kind of quick long circulating liposomes of paclitaxel pH that the present invention provides, also have a characteristic that i.e.,
Above-mentioned pH sensitivity film material is selected from NIPA and derivant, two Palmic acid phospholipid and derivant, senior fat
One in fat acid phospholipid and derivant, polyoxyethylene acyl hydramine and derivant, dioleoyl ethanolamine and derivant thereof or
Several.
The most such as: two Palmic acid phospholipid, heptadecanoic acid phospholipid, dioleoyl ethanolamine etc..
Further, a kind of quick long circulating liposomes of paclitaxel pH that the present invention provides, also have a characteristic that i.e.,
Above-mentioned phospholipid is the phospholipid that surface is carried out by hydrophilic material modifying.
Further, a kind of quick long circulating liposomes of paclitaxel pH that the present invention provides, also have a characteristic that i.e.,
Above-mentioned phospholipid is sweet selected from dipalmitoyl phosphatidyl choline, Phosphatidylserine, phosphatidylinositols, PHOSPHATIDYL ETHANOLAMINE, phosphatidyl
Oil, phosphatidylcholine, two Cetyl Phosphates, dimyristoyl phosphatidyl choline, distearoyl phosphatidylcholine, two lauroyl phosphorus
Phosphatidylcholine, DOPC, DSPE.
The most such as: molecular weight is the PEG of 1000-10000, molecular weight is the AEO of 1000-10000, molecular weight is 1000-
One or more in the non-ionic polyacrylamide of 10000.
Further, a kind of quick long circulating liposomes of paclitaxel pH that the present invention provides, also have a characteristic that aquation
Dielectric material is the buffer solution of 3-6 selected from pH.
Further, a kind of quick long circulating liposomes of paclitaxel pH that the present invention provides, also have a characteristic that i.e.,
Above-mentioned buffer solution delays selected from tartaric acid/sodium tartrate buffer solution, acetic acid/acetate buffer solution, citrate buffer solution, citric acid
Rush the one in liquid, sodium formate buffer, acetic acid/sodium-acetate buffer, acetic acid/ammonium acetate buffer, phosphoric acid class buffer.
It addition, present invention also offers the preparation method of above-mentioned a kind of quick long circulating liposomes of paclitaxel pH, its feature exists
In, concrete technology step is as follows:
Step one, paclitaxel, cholesterol, pH sensitivity film material, hydrophilic material are dissolved in organic solvent, be configured to A,
B, C, solution D；Above-mentioned A, B, C, the mass percent concentration of solution D are 10-85%.
Aqueous vehicles material is dissolved in water for injection, regulates pH to 3-6, configure aqueous vehicles；
Step 2, B is added in A, mixing；
Step 3, be sequentially added into C and D after,；
Step 4, regulation pH to 3-6；
Step 5, the product of step 4 is revolved and steams, film forming；
Step 6, addition aqueous vehicles, aquation；
Step 7, after homogenizing at least one times, aseptic filtration, subpackage i.e. obtains the injection quick liposome of paclitaxel pH.Typically
Select the scheme of repeatedly homogenizing under the most multiple pressure environment.
Further, the preparation method of above-mentioned a kind of quick long circulating liposomes of paclitaxel pH that the present invention also provides for, also have
Have the particular feature that i.e.,
In step one, one or more in alcohols, halogenated hydrocarbon, ethers, arene of organic solvent；As: second
Alcohol, methanol, propanol, chloroform, dichloromethane, carbon tetrachloride, ether, dimethyl ether, diethyl ether, oxolane, dioxane, benzene,
Toluene equal solvent.It preferably is selected from the boiling point solvent less than 85 DEG C.
In step 2, B is added the maximal rate that the speed in A can become rapidly clarification with mixed liquor and is advisable；
In step 5, the step that rotation is steamed is carried out 1-3 hour under the water bath condition of 50-80 DEG C；
In step 6, the step of aquation is carried out 1-3 hour under the water bath condition of 50-80 DEG C；
In step 7, the step of homogenizing is carried out under the water bath condition of 50-80 DEG C, homogenization pressure be 0-10000bar not
Deng.
The effect of the present invention and effect:
The liposome that the present invention provides, solves the water-insoluble shortcoming of paclitaxel, reduces poison secondary compared with existing preparation
Effect, due to its long action time, thus extends administration time, improves the compliance of patient, also improve chemotherapy simultaneously
The targeting of drug taxol, enhances its antitumor action.
Meanwhile, the quick liposome of pH that the present invention provides is the liposome sensitive to pH change (particularly to low pH), selects
Lipid materials to pH sensitivity, the most such as: two Palmic acid phospholipid or heptadecanoic acid phospholipid are that film material is prepared as the quick fat of medicine carrying pH
Plastid.
Owing to, under human normal state, the pH value of body should maintain between 7.3～7.4, the most slightly in alkalescence.Because tumor
Cell is faster than normal cell growth, and does not often catch up with the foot of tumor cell rapid amplifying in the supply of tumor tissues medium vessels
Step, the oxygen of supply and nutriment are not enough.Tumor cell is always in the microenvironment of anoxia and scarce nutriment growth, metabolism mistake
Journey is also different from normal cell, generates the acidic metabolites such as more lactic acid so that the tissue of solid tumor tissue periphery
Liquid pH value reduces.Owing to the pH of mesenchyma stroma of tumors is lower than the pH of normal surrounding tissue cell, therefore select the present invention provide to pH
Sensitive lipoidis material makes liposome, when this liposome enters into tumor locus, owing to the reduction of pH causes fatty acid
The non-phase Rotating fields of substrate chemical conversion hexagonal crystal phase, so that film merges, can realize the effect of accelerated release in vitro.Such that it is able to raising medicine
The targeting of thing, reduces dosage, reduces the side effect that medicine brings.
It addition, select the phospholipid that (such as: PEG etc.) water wetted material is modified as the raw material preparing liposome in the present invention
One of, a kind of liposome through being modified can be obtained by water wetted material, this structure increases compliance and the hydrophilic of liposome, logical
Cross the phagocytosis of monocytes/macrophages system, reduce the interaction of liposome adipose membrane and plasma protein, extend circulation time, favorably
The absorption to medicine in tumor tissues and pathogenic site, and then realize macrocyclic effect.This long circulating liposomes is conducive to liver
Tissue beyond spleen or the targeting of organ.Meanwhile, antibody or part are combined in the end of PEG, both can keep long circulating,
The identification to target body can be kept again.
Detailed description of the invention
Embodiment one,
| Paclitaxel | 0.5g |
| Injection succinic acid half-ester cholesterol | 2.8g |
| Dioleoyl ethanolamine | 4.2g |
| PEG2000-DSPE | 0.2g |
| Tartaric acid | 12g |
| Sodium tartrate | 27g |
By the paclitaxel of recipe quantity, injection succinic acid half-ester cholesterol, dioleoyl ethanolamine, PEG2000-DSPE is dissolved in
The ethanol of 95% is respectively in (can also be methanol, chloroform, dichloromethane etc.) A, B, C, solution D.
A is poured in three-necked bottle；Under agitation, by glass dropping pipe B at the uniform velocity added in A (speed is to add mixing
Liquid can become rapidly the maximal rate of clarification and be advisable.) mix about 1min after the entry to be completely.C is added in three-necked bottle, treat to add completely
About 1min is mixed after entering.Slowly being sequentially added into C and solution D, after being added completely into, with 1.25MHCl solution, (final holding solution is clear
Regulation pH clearly) is 5.4.Reactant liquor is added in the rotary evaporator in water-bath, control rotating speed, 65 DEG C of rotary evaporations 2 hours.
The tartaric acid of recipe quantity, sodium tartrate are dissolved in water for injection, add 1.25M HCl and adjust pH to 5.25.Take
Above-mentioned aqueous vehicles adds in revolving bottle, 65 DEG C of aquations 2 hours.Treat 65 DEG C of homogenizer homogenizing (0bar3 time, 200bar3 time,
800bar5 time), use subpackage after 0.22um polyether sulfone filter element aseptic filtration i.e. to obtain the injection quick liposome of paclitaxel pH.
Embodiment two,
| Paclitaxel | 0.5g |
| Injection cholesterol | 0.8g |
| Dioleoyl ethanolamine | 4.2g |
| PEG2000-DSPE | 0.2g |
| Tartaric acid | 12g |
| Sodium tartrate | 27g |
By the paclitaxel of recipe quantity, injection cholesterol, dioleoyl ethanolamine, PEG2000-DSPE is dissolved in organic solvent
It is respectively A, B, C, solution D.A is poured in three-necked bottle；Under agitation, drip pipe by glass and B is at the uniform velocity added (speed in A
The maximal rate that can become rapidly clarification with addition mixed liquor is advisable.) mix about 1min after the entry to be completely.C is added three-necked bottle
In, mix about 1min after the entry to be completely.Being slowly added to 1.25M HCl solution (final holding solution clarification) is 5.4 to pH.Treat
Mix after being added completely into.Reactant liquor is added in the rotary evaporator in water-bath, control rotating speed, rotary evaporation.
The tartaric acid of recipe quantity, sodium tartrate are dissolved in water for injection, add 1.25M HCl and adjust pH to 5.25.Take
Above-mentioned aqueous vehicles adds in revolving bottle, aquation.After homogenizer homogenizing, aseptic filtration, subpackage i.e. obtains the quick lipid of paclitaxel pH
Body.
Embodiment three,
| Paclitaxel | 1.4g |
| Injection cholesterol | 4.8g |
| DPPA | 2.5g |
| PEG1000-DLPC | 0.1g |
| Citrate buffer solution | 39.8g |
By the paclitaxel of recipe quantity, injection cholesterol, DPPA, PEG1000-DLPC is dissolved in organic solvent
It is respectively A, B, C, solution D.A is poured in three-necked bottle；Under agitation, drip pipe by glass and B is at the uniform velocity added (speed in A
The maximal rate that can become rapidly clarification with addition mixed liquor is advisable.) mix about 1min after the entry to be completely.C is added three-necked bottle
In, mix about 1min after the entry to be completely.Being slowly added to 1.25M HCl solution (final holding solution clarification) is 6 to pH.Treat
Mix after full addition.Reactant liquor is added in the rotary evaporator in water-bath, control rotating speed, rotary evaporation.
The citric acid/sodium citrate of recipe quantity is dissolved in water for injection, adds 1.25M HCl and adjust pH to 6.Take above-mentioned
Aqueous vehicles adds in revolving bottle, aquation.After homogenizer homogenizing, aseptic filtration, subpackage i.e. obtains the quick liposome of paclitaxel pH.
Embodiment four,
| Paclitaxel | 1g |
| Injection cholesterol | 0.7g |
| Dioleoyl ethanolamine | 7.2g |
| AEO1000-DPPC | 0.4g |
| Tartaric acid | 15g |
| Sodium tartrate | 28g |
By the paclitaxel of recipe quantity, injection cholesterol, dioleoyl ethanolamine, AEO1000-DPPC is dissolved in organic solvent
It is respectively A, B, C, solution D.A is poured in three-necked bottle；Under agitation, drip pipe by glass and B is at the uniform velocity added (speed in A
The maximal rate that can become rapidly clarification with addition mixed liquor is advisable.) mix about 1min after the entry to be completely.C is added three-necked bottle
In, mix about 1min after the entry to be completely.Being slowly added to 1.25M HCl solution (final holding solution clarification) is 5.4 to pH.Treat
Mix after being added completely into.Reactant liquor is added in the rotary evaporator in water-bath, control rotating speed, rotary evaporation.
The tartaric acid of recipe quantity, sodium tartrate are dissolved in water for injection, add 1.25M HCl and adjust pH to 5.25.Take
Above-mentioned aqueous vehicles adds in revolving bottle, aquation.After homogenizer homogenizing, aseptic filtration, subpackage i.e. obtains the quick lipid of paclitaxel pH
Body.
Embodiment five,
| Paclitaxel | 1.5g |
| Injection succinic acid half-ester cholesterol | 0.5g |
| Heptadecanoic acid phospholipid | 2.5g |
| AEO1000-DPPC | 0.5g |
| Acetic acid | 15g |
| Sodium acetate | 30g |
The paclitaxel of recipe quantity, injection succinic acid half-ester cholesterol, heptadecanoic acid phospholipid, AEO1000-DPPC are dissolved in
Organic solvent is respectively A, B, C, solution D.A is poured in three-necked bottle；Under agitation, by glass dropping pipe, B is at the uniform velocity added
Enter in A that (speed can become rapidly the maximal rate of clarification and is advisable adding mixed liquor.) mix about 2min after the entry to be completely.By C
Add in three-necked bottle, mix about 5min after the entry to be completely.It is slowly added to 1.25M HCl solution (final holding solution clarification) extremely
PH is 3.Mix after the entry to be completely.Reactant liquor is added in the rotary evaporator in water-bath, control rotating speed, rotary evaporation.
The acetic acid of recipe quantity, sodium acetate are dissolved in water for injection, add 1.25M HCl and adjust pH to 3.4.Take above-mentioned water
Change medium and add in revolving bottle, aquation.After homogenizer homogenizing, aseptic filtration, subpackage i.e. obtains the quick liposome of paclitaxel pH.
Claims (10)
1. the quick long circulating liposomes of paclitaxel pH, it is characterised in that by the material preparation of following mass percentage content
Become:
2. a kind of quick long circulating liposomes of paclitaxel pH as claimed in claim 1, it is characterised in that:
Described pH sensitivity film material is selected from NIPA and derivant, two Palmic acid phospholipid and derivant, height
Level Fatty acids Phospholipids and derivant, polyoxyethylene acyl hydramine and derivant, dioleoyl ethanolamine and derivant thereof in one
Plant or several.
3. a kind of quick long circulating liposomes of paclitaxel pH as claimed in claim 1, it is characterised in that:
Described hydrophilic material is the phospholipid that surface is carried out by hydrophilic material modifying.
4. a kind of quick long circulating liposomes of paclitaxel pH as claimed in claim 3, it is characterised in that:
Described phospholipid is selected from dipalmitoyl phosphatidyl choline, Phosphatidylserine, phosphatidylinositols, PHOSPHATIDYL ETHANOLAMINE, phospholipid
Acyl glycerol, phosphatidylcholine, two Cetyl Phosphates, dimyristoyl phosphatidyl choline, distearoyl phosphatidylcholine, two Laurels
Phosphatidyl choline, DOPC, DSPE.
5. a kind of quick long circulating liposomes of paclitaxel pH as claimed in claim 1, it is characterised in that:
Described hydrophilic material selected from molecular weight be the PEG of 1000-10000, molecular weight be the AEO of 1000-10000, molecular weight
For one or more in the non-ionic polyacrylamide of 1000-10000.
6. a kind of quick long circulating liposomes of paclitaxel pH as claimed in claim 1, it is characterised in that:
Described aqueous vehicles material is the buffer solution of 3-6 selected from pH.
7. a kind of quick long circulating liposomes of paclitaxel pH as claimed in claim 6, it is characterised in that:
Described buffer solution is selected from tartaric acid/sodium tartrate buffer solution, acetic acid/acetate buffer solution, citrate buffer solution, citron
In acid buffer, sodium formate buffer, acetic acid/sodium-acetate buffer, acetic acid/ammonium acetate buffer, phosphoric acid class buffer one
Kind.
8. a kind of quick long circulating liposomes of paclitaxel pH as claimed in claim 1, it is characterised in that by following mass percent
The material of content is prepared from:
9. the preparation method of a kind of quick long circulating liposomes of paclitaxel pH as described in claim 1-8 is arbitrary, it is characterised in that
Concrete technology step is as follows:
Step one, paclitaxel, cholesterol, pH sensitivity film material, hydrophilic material are dissolved in organic solvent, be configured to A, B, C,
Solution D；
Aqueous vehicles material is dissolved in water for injection, regulates pH to 3-6, configure aqueous vehicles；
Step 2, B is added in A, mixing；
Step 3, be sequentially added into C and D after, mixing；
Step 4, regulation pH to 3-6；
Step 5, the product of step 4 is revolved and steams, film forming；
Step 6, addition aqueous vehicles, aquation；
Step 7, after homogenizing at least one times, aseptic filtration, subpackage i.e. obtains the injection quick liposome of paclitaxel pH.
10. the preparation method of a kind of quick long circulating liposomes of paclitaxel pH stated such as claim 9, it is characterised in that: step one
In, one or more in alcohols, halogenated hydrocarbon, ethers, arene of organic solvent；In step 2, B is added in A
The speed maximal rate that can become rapidly clarification with mixed liquor be advisable；
In step 5, the step that rotation is steamed is carried out 1-3 hour under the water bath condition of 50-80 DEG C；
In step 6, the step of aquation is carried out 1-3 hour under the water bath condition of 50-80 DEG C；
In step 7, the step of homogenizing is carried out under the water bath condition of 50-80 DEG C, and homogenization pressure is 0-10000bar.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610835887.5A CN106309370A (en) | 2016-09-20 | 2016-09-20 | Paclitaxel pH-sensitive long-circulation liposome and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610835887.5A CN106309370A (en) | 2016-09-20 | 2016-09-20 | Paclitaxel pH-sensitive long-circulation liposome and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106309370A true CN106309370A (en) | 2017-01-11 |
Family
ID=57788128
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610835887.5A Pending CN106309370A (en) | 2016-09-20 | 2016-09-20 | Paclitaxel pH-sensitive long-circulation liposome and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106309370A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110981837A (en) * | 2019-12-03 | 2020-04-10 | 沈阳药科大学 | Paclitaxel weakly acidic derivative active drug-loaded liposome and preparation and application thereof |
| CN111329838A (en) * | 2020-05-09 | 2020-06-26 | 南京绿叶制药有限公司 | Paclitaxel liposome pharmaceutical composition and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1509166A (en) * | 2001-03-26 | 2004-06-30 | Liposome composition for improved intracellular delivery of therapeutic agent | |
| CN1846692A (en) * | 2006-05-15 | 2006-10-18 | 沈阳药科大学 | Long circulation liposome prepn of polyene taxol and its prepn process |
| CN102274185A (en) * | 2011-08-10 | 2011-12-14 | 山东大学 | Antitumor pH-sensitive liposome and freeze-dried powder injection thereof, and preparation methods thereof |
| CN104193779A (en) * | 2014-08-22 | 2014-12-10 | 四川大学 | PH-sensitive phospholipid medicinal material as well as preparation method and application thereof |
-
2016
- 2016-09-20 CN CN201610835887.5A patent/CN106309370A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1509166A (en) * | 2001-03-26 | 2004-06-30 | Liposome composition for improved intracellular delivery of therapeutic agent | |
| CN1846692A (en) * | 2006-05-15 | 2006-10-18 | 沈阳药科大学 | Long circulation liposome prepn of polyene taxol and its prepn process |
| CN102274185A (en) * | 2011-08-10 | 2011-12-14 | 山东大学 | Antitumor pH-sensitive liposome and freeze-dried powder injection thereof, and preparation methods thereof |
| CN104193779A (en) * | 2014-08-22 | 2014-12-10 | 四川大学 | PH-sensitive phospholipid medicinal material as well as preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| 李维凤等: "《药学专业知识.1》", 30 April 2015 * |
| 梅兴国: "《微载体药物递送系统》", 30 November 2009 * |
| 王一婕: "二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT)脂质体的制备及其体内药代动力学研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
| 郭慧玲等: "《药剂学》", 28 February 2014 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110981837A (en) * | 2019-12-03 | 2020-04-10 | 沈阳药科大学 | Paclitaxel weakly acidic derivative active drug-loaded liposome and preparation and application thereof |
| CN111329838A (en) * | 2020-05-09 | 2020-06-26 | 南京绿叶制药有限公司 | Paclitaxel liposome pharmaceutical composition and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jing et al. | A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier for paclitaxel | |
| US9814734B2 (en) | Bufalin liposome, preparation method therefor and application thereof | |
| CN112451487A (en) | Curcumin active drug-loaded liposome and preparation method thereof | |
| CN105853403B (en) | A kind of paclitaxel palmitate liposome and preparation method thereof | |
| WO2011066684A1 (en) | Liposome of irinotecan or its hydrochloride and preparation method thereof | |
| WO2022160971A1 (en) | Concentrate containing poorly soluble drug, and emulsion prepared therefrom | |
| WO2022160970A1 (en) | Concentrated solution of insoluble drug not containing ethanol, and micellar solution prepared therefrom | |
| CN109224084A (en) | TPGS modification docetaxel liposome administration nano-drug administration system and and preparation method thereof, application | |
| CN103405385B (en) | A kind of temozolomide's intravenous injection fatty breast and preparation method thereof | |
| CN106692059B (en) | A kind of hypoxemia response lipidosome drug carrier and the preparation method and application thereof | |
| CN101524329B (en) | Bicyclo-ethanol submicron emulsion and preparation method thereof | |
| CN102188439B (en) | Nanoparticle liposome for releasing different medicines in programmed manner and preparation and use thereof | |
| CN1706371B (en) | Efficient sword-like iris seed preparation and its preparation process | |
| CN109718228A (en) | The antitumor Lymph Node Metastasis of mitoxantrone acts on and its pharmaceutical preparation | |
| CN101829052A (en) | Self-emulsifying preparation of taxane compound and preparation method thereof | |
| CN102552137B (en) | Triptolide fat emulsion injection and preparation method thereof | |
| CN102274188A (en) | Solid lipid nanoparticles comprising andrographolide and preparation method and application thereof | |
| CN106309370A (en) | Paclitaxel pH-sensitive long-circulation liposome and preparation method thereof | |
| CN100479820C (en) | Itraconazole liposome and preparation process thereof | |
| CN108743534B (en) | Tripterine or tripterine derivative vesicle and preparation method thereof | |
| CN104546722B (en) | Miriplatin lipidosome and preparation method thereof | |
| CN108721643B (en) | pH sensitive liposome for immune chemotherapy | |
| CN110464708A (en) | A kind of spirulina nanometer formulation and preparation method thereof | |
| CN111481559B (en) | High-concentration fulvestrant composition and preparation method thereof | |
| CN107802600B (en) | Icariin bone targeting nano liposome as well as preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170111 |