CN105616354A - Neogambogic acid liposome injection and preparation method thereof - Google Patents
Neogambogic acid liposome injection and preparation method thereof Download PDFInfo
- Publication number
- CN105616354A CN105616354A CN201410622327.2A CN201410622327A CN105616354A CN 105616354 A CN105616354 A CN 105616354A CN 201410622327 A CN201410622327 A CN 201410622327A CN 105616354 A CN105616354 A CN 105616354A
- Authority
- CN
- China
- Prior art keywords
- neogambogic acid
- acid
- neogambogic
- peg
- lipid
- 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
Abstract
The invention specifically relates to a neogambogic acid liposome injection and a preparation method thereof, belonging to the field of medicinal preparations. The neogambogic acid liposome injection comprises, by weight, 0.01 to 10% of neogambogic acid, 0.005 to 5% of a phosphatide material, 0.001 to 2% of cholesterol, 0.005 to 1.5% of pegylated lipid, 0.0025 to 2.5% of organic acid or ammonium sulfate, 0.1 to 25% of sugar and 0.1 to 15% of a buffering agent, with the balance being injection water. The neogambogic acid liposome injection provided by the invention improves the solubility of neogambogic acid and bioavailability of neogambogic acid in the body, prolongs in-vivo action time of neogambogic acid, reduces irritation and other toxic and side effects of neogambogic acid and better performs the biologically active anticancer treatment effect of neogambogic acid.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of neogambogic acid lipidosome injection and preparation method thereof, internal reticuloendothelial system phagocytic a kind of neogambogic acid lipidosome injection that can stably store and preparation method thereof is helped avoid it is more particularly related to a kind of.
Background technology
Neogambogic acid is isolated a kind of compound with relatively high anti-tumor activity from Chinese medicine gamboge, and its antimicrobial spectrum is relatively wide, and toxicity is relatively low, act on tumor cell to the property of can select that, and intact animal's hemopoietic system and immune system are not affected, body well-tolerated, to leukemia L1210, S180Ehrlich ascites carcinoma, Lewis lung cancer, La795 adenocarcinoma of lung, cancer of pancreas, gastric cancer, the entity tumor such as hepatocarcinoma all has good inhibiting effect, and wherein the anti-tumor activity of neogambogic acid is about 2 times of gamlogic acid, and neogambogic acid can effectively block cancerous cell at G0~G1Phase, and then suppress the growth of tumor cell, promoting the apoptosis of tumor cell, prompting neogambogic acid is the very potential cancer treatment drugs of one.
Neogambogic acid molecular formula: C38H46O9, molecular weight 631.0, structural formula:
Liposome (liposome) means micro-bubbles utricule drug encapsulation formed in lipoids bilayer, is a kind of synthetic membrane. In water, phospholipid molecule hydrophilic head inserts in water, and liposome hydrophobic tail stretches to air, forms the spherical liposomes of double-deck fat molecule after stirring, and diameter 25 ~ 1000nm is not etc. When amphiphatic molecule such as phospholipid and sphingolipid are scattered in aqueous phase, the hydrophobic tail of molecule is tended to flock together, and avoids aqueous phase, and hydrophilic head is exposed to aqueous phase, formed have bilayer structure vesicle, be called liposome. Liposome can be used for transgenic, or loads medicine, utilizes liposome with the feature of cell membrane fusion, medicine can be sent into cell interior. The preparation method of liposome has: injection method, film dispersion method, ultrasonic dispersion, reverse evaporation.
After nineteen sixty-five Bangham finds liposome, Gregoriadis and Rymen reported first in 1971 using liposome as pharmaceutical carrier, the end of the seventies in last century, liposome was initially as the effective carrier of anthracene ring antitumor medicinal, liposome is the bimolecular folliculus of similar biofilm structure, it it is the vesicle with single or multiple double-layer quantum dots, its main component is phospholipid, in phospholipid molecule, the part of phosphoric acid group has strong polarity (hydrophilic), and hydrocarbon chain has nonpolar (hydrophobicity). Have an advantage that 1) internal biodegradable, immunogenicity is little; 2) water-soluble and fat-soluble medicine all can embed delivery, medicament slow release, and duration of efficacy is long; 3) by cell endocytic fusion, medicine can directly be made a gift to someone in cell by liposome, it is to avoid uses high concentration free drug thus reducing untoward reaction; 4) normal structure capillary wall is complete, and most liposome can not permeate, and the permeability of tumor location blood capillary increases, and makes liposome medicament aggregate amount increase, and due to the slow release of medicine, is directly used in tumor locus, adds therapeutic effect. Liposome medicament enters after human circulation mainly by the leukocyte in reticuloendothelial system (reticuloendothelialsystem, RES), mononuclear cell and macrophage phagocytic, and this has special meaning for the treatment of RES tumor. Early stage liposome medicament application because of poor stability, medicine easy to leak, the shelf life is short, tissue-targeting is poor and is easily restricted by RES removing rapidly etc.; Wrap up now the liposome of polymer substance Polyethylene Glycol on its surface because its composition contains hydrophilic polymer, the hydrophilic on its surface can have been improved. The liposome of Polyethylene Glycol can stop plasma protein to adsorb, and nurses one's health in surface of liposome, and the phagocytosis reducing RES absorbs, and the interception of escape from immune system extends medicine circulation time in vivo, so generally also referred to as long circulating liposomes. The domestic liposome medicament listed the earliest is the injection Paclitaxel liposome that Nanjing Lvye Sike Pharma Co., Ltd. produces, subsequently, there are the Doxil injection that Changzhou Jinyuan Drug Industry Manufacturing Co., Ltd, Shanghai Fudan Zhangjiang biomedical Co., Ltd, Zhongqi Pharmaceutical Technology (Shijiazhuang) Co. Ltd. of Shiyao Group produce and the Amphotericin B for injection liposome of Shanghai Xinxianfeng Pharmaceutical Co., Ltd., Shanghai Xinya Pharmaceutical Industry Co. Ltd.'s production successively.
Neogambogic acid is glassy yellow amorphous powder, mp65 ~ 68 DEG C, at ethanol, the organic solvents such as methanol dissolve, in water insoluble, it is dissolved in organic solvent and sig water, there is optical activity, to ferric chloride in blueness, owing to neogambogic acid dissolubility in aqueous is low, after injection body zest is big, Half-life in vivo is short, limit its application clinically, it is thus desirable to use Modern preparations technology to be effectively improved the dissolubility of neogambogic acid, reduce zest, extend medicine action time in vivo and localized clusters amount, better play antitumaous effect, patent disclosed in inventor's early stage (Authorization Notice No. is CN101947204A) described neogambogic acid solid lipid nanoparticle and preparation method thereof, although solving the water solublity of neogambogic acid, the problems such as zest, but it is in stability and drug loading a bit deficient in, it is easily subject to humidity, temperature, the impact of illumination and oxidation Decomposition, the preparation method of patent disclosed in inventor's early stage (Authorization Notice No. is CN101879137B) described a kind of hidden liposome, the preparation method that this invention relates to a kind of hidden liposome, the method adopts secondary lyophilization, prepare into neogambogic acid hidden liposome, but this preparation method needs secondary lyophilizing, complex manufacturing is not suitable for industrialized production, and production cost is also high, there is the shortcomings such as organic removal of solvents is not clean in production technology, Anhui medicine, 13 (6): 596��598,2009 inventors disclose preparation and the entrapment efficiency determination thereof of the lipidosome freeze-dried powder of neogambogic acid, this section of article have studied the lipidosome freeze-dried powder of neogambogic acid, but this liposome does not add macrocyclic Pegylation fat, the neogambogic acid liposome prepared by the method enters in body and is easily swallowed by internal liver spleen reticuloendothelial system. described these all bring restriction to neogambogic acid in actual production and clinical practice, so the present invention is a kind of neogambogic acid lipidosome injection of preparation on the basis of early stage patent or research, the present invention improves the dissolubility of neogambogic acid and the bioavailability in body, reduce zest to body, extend medicine effect such as action time in body. neogambogic acid lipidosome injection provided by the invention, has the advantage that
1. the neogambogic acid liposome of the present invention improves the dissolubility of neogambogic acid, reduces zest, extends medicine action time in vivo and localized clusters amount, better plays antitumaous effect, reduce the toxic and side effects of neogambogic acid, improve the toleration of body;
2. the preparation of the present invention can overcome solid lipid nanoparticle to place row, the phenomenon that envelop rate is low outside process Chinese medicine, and neogambogic acid liposome drug loading is higher, performance is more stable, and preparation can stably be stored;
3. compared with the Emulsion of neogambogic acid, solid lipid nanoparticle etc., the preparation of the present invention is modified by long circulating adjuvant nanoparticle surface, help avoid the phagocytosis of internal liver spleen reticuloendothelial system, and there is slow-release function, it is possible to extend medicine circulation time in vivo.
Summary of the invention
Neogambogic acid medicine for above-mentioned prior art and our oneself separation purification, the present invention provides the novel medicine carrying body neogambogic acid liposome of a kind of neogambogic acid, neogambogic acid liposome drug loading of the present invention is higher, performance is more stable, and preparation can stably be stored. Another object of the present invention is to the preparation method that a kind of neogambogic acid liposome preparing the present invention is provided.
Neogambogic acid is wrapped in the bimolecular folliculus of the similar biofilm structure of liposome by the present invention, add the dissolubility of neogambogic acid, greatly reducing zest, preparation reaches the effects such as more specific targeting, controlled release to a certain extent, and physicochemical properties are stable.
For achieving the above object, the invention provides a kind of neogambogic acid liposome, it is being made up of by therapeutically effective amount substantially neogambogic acid, phospholipid material, cholesterol, lipid adjuvant, organic acid or ammonium sulfate, sugar, buffer agent, water for injection etc.
Specifically, in technique scheme, neogambogic acid liposome provided by the invention contains following ingredients:
Neogambogic acid 0.01��10%
Phospholipid material 0.005��5%
Cholesterol 0.001��2%
Pegylation fat 0.005��1.5%
Organic acid or ammonium sulfate 0.0025��2.5%
Sugar 0.1��25%
Buffer agent 0.1��15%
All the other add to appropriate for water for injection composition
Preferred formula is composed as follows:
Neogambogic acid 10g
Hydrogenated soy phosphatidyl choline 66g
Cholesterol 10g
Pegylation fat 8g
Organic acid or ammonium sulfate 5g
Sugar 800g
Buffer agent 50g
Water for injection adds to 1000mL
Described phospholipid material is selected from Ovum Gallus domesticus Flavus lecithin, hydrogenated yolk lecithin, soybean lecithin, hydrogenated soy phosphatidyl choline, DLPC, two myristoyl lecithin, DPPC, distearoylphosphatidylcholine, MPPC, PMPC, PSPC, SPPC, DOPC, two myristoyl phosphatidic acid, DPPA, two myristoyl phospholipid phthalein ethanolamine, two palmityl phospholipid phthalein ethanolamine, cephalin acyl serine, cranial nerve sphingomyelins, two palm fibres put phthalein sphingomyelin, distearyl sphingomyelin, one or more of DSPE, but it is not limited to this.
Described Pegylation fat is the stearate of 1000 ~ 10000Da selected from PEG molecular weight, PEG molecular weight is 1000 ~ 10000Da vitamin e succinate, methoxyl group PEG2000-distearoylphosphatidyl ethanol ammonium, cholesterol-PEG, dialycerides-PEG, DSPE multi-arm PEG or DSPE multi-arm PEG, PEG stearate and molecular weight are the mixture of the PEG of 200 ~ 10000Da, Myrj class, Brij class, PEG DSPE, PEG dipalmitoyl phosphatidyl choline, PEG DPPE, ganglioside, polyacrylamide, chitosan, Polyethylene Glycol gathers cetyl itrile group propionic ester, molecular weight is the PEG of 200 ~ 10000Da, one or more combination in any of PVP or PVA, but it is not limited to this.
Sugar is selected from one or more combination in any of trehalose, sucrose, mannitol, glucose, sodium chloride, lactose, sorbitol, xylitol, glucosan, Polyethylene Glycol, polyvinylpyrrolidone, dextran, glycerol or glycine, but is not limited to this.
Buffer agent is selected from histidine or glycine, but is not limited to this.
The preparation method that present invention also offers a kind of neogambogic acid liposome, the method comprises the following steps:
(1) neogambogic acid and the phospholipid material of claim 1, cholesterol, lipid adjuvant are added heat fusing or organic solvent dissolution, make lipid soln;
(2) lipid soln is put the evaporation of rotary evaporator rotating thin film, makes lipid membrane;
(3) by lipid membrane with the organic acid containing claim 1 or ammonium sulfate, sugar, aqueous solution of buffer agent hydration, concussion, or the lipid soln in (1) is directly mixed with aqueous solution concussion, make lipid aqueous dispersion;
(4) lipid aqueous dispersion is carried out emulsifying ultrasonic, homogeneous, microjet, press filtration process, thus preparing neogambogic acid liposome.
Further prepared neogambogic acid liposome can be carried out frozen dried or be placed in 4 DEG C of lower seals preservations, the technique that obtained neogambogic acid liposome wherein carries out frozen dried is: by 1 ~ 40%(weight ratio) freeze drying protectant be dissolved in the aqueous dispersion of neogambogic acid liposome of the present invention, this freeze drying protectant is selected from trehalose, sucrose, mannitol, glucose, sodium chloride, lactose, sorbitol, xylitol, glucosan, Polyethylene Glycol, polyvinylpyrrolidone, dextran, one or more combination in any of glycerol or glycine, but it is not limited to this, better to ensure formation lyophilized powder crystal formation, then it is divided in cillin bottle, it is placed in freezer dryer-45 DEG C of pre-freeze 2.5h, then it is warming up to-50 DEG C at 5 DEG C/h, maintain 10h, it is warming up to 0 DEG C again with 5 DEG C/h, maintain 8h, finally be warming up to 10 DEG C insulation 10h after outlet, jump a queue and seal.
Described organic solvent is selected from one or more combination in any of dichloromethane, chloroform, acetone, isopropyl acetone, methanol, ethanol, ether, oxolane, dimethyl carbonate, the tert-butyl alcohol, chlorobutanol, ethyl acetate, propylene glycol, dimethyl sulfone, petroleum ether or isopropanol, but is not limited to this.
Detailed description of the invention:
With embodiment, the present invention is further described and provides implementation detail more below.
Embodiment 1:
. 10g neogambogic acid is put rotary evaporator with hydrogenated soy phosphatidyl choline 66g, cholesterol 10g, Pegylation fat 8g and adds heat fusing, rotate, make lipid membrane; By lipid membrane with liquid containing ammonium sulfate 5g, sucrose 800g, glycine 5g aqueous solution hydration, concussion, make lipid aqueous dispersion; Lipid aqueous dispersion carries out emulsifying ultrasonic, homogeneous, microjet, extruding process with the filtering with microporous membrane of 0.80 ��m, 0.45 ��m, 0.25 ��m respectively, thus preparing neogambogic acid liposome turbid liquor; In the cillin bottle containing 7mg lactose, add 1mL neogambogic acid liposome turbid liquor, put into lyophilization in vacuum freeze drier (see freeze-drying curve 1), the neogambogic acid lipidosome injection lyophilized injectable powder namely made.
Freeze-drying curve 1:
Operation programming rate time (h) temperature (DEG C)
(1) pre-freeze 3 room temperature is to-30 DEG C��-50 DEG C
(2) insulation 1.5-50 DEG C
(3) evacuation 0.5-30 DEG C��-50 DEG C
(4) intensification is warming up to-5 DEG C for 5 DEG C/h 6
(5) intensification 5 DEG C/h 4-5 DEG C is warming up to 0 DEG C
(6) heat up 5 DEG C/h 30 DEG C to 10 DEG C
(7) heat up 5 DEG C/h 310 DEG C to 25 DEG C
(8) insulation 225 DEG C
Embodiment 2:
10g neogambogic acid is put rotary evaporator with hydrogenated soy phosphatidyl choline 66g, cholesterol 10g, Pegylation fat 8g and adds heat fusing, rotate, make lipid membrane; By lipid membrane with liquid containing ammonium sulfate 5g, sucrose 800g, glycine 5g aqueous solution hydration, concussion, make lipid aqueous dispersion; Lipid aqueous dispersion carries out emulsifying ultrasonic, homogeneous, microjet, extruding process with the filtering with microporous membrane of 0.80 ��m, 0.45 ��m, 0.25 ��m respectively, 1mL suspension is added in the cillin bottle containing 10mg lactose, put into lyophilization in vacuum freeze drier (see freeze-drying curve 2), the neogambogic acid lipidosome injection lyophilized injectable powder namely made.
Freeze-drying curve 2:
Operation programming rate time (h) temperature (DEG C)
(1) pre-freeze 3 room temperature is to-30 DEG C��-50 DEG C
(2) insulation 1.5-30 DEG C��-50 DEG C
(3) evacuation 0.5-30 DEG C��-50 DEG C
(4) intensification is warming up to-5 DEG C for 5-10 DEG C/h 6
(5) intensification 5-10 DEG C/h 4-5 DEG C is warming up to 0 DEG C
(6) intensification 5-10 DEG C/h 30 DEG C to 10 DEG C
(7) intensification 5-10 DEG C/h 310 DEG C to 25 DEG C
(8) insulation 225 DEG C
Embodiment 3:
10g neogambogic acid is put rotary evaporator with hydrogenated soy phosphatidyl choline 66g, cholesterol 10g, Pegylation fat 8g and adds heat fusing, rotate, make lipid membrane; By lipid membrane with liquid containing ammonium sulfate 5g, sucrose 800g, glycine 5g aqueous solution hydration, concussion, make lipid aqueous dispersion; Lipid aqueous dispersion carries out emulsifying ultrasonic, homogeneous, microjet, extruding process with the filtering with microporous membrane of 0.80 ��m, 0.45 ��m, 0.25 ��m respectively, 1mL suspension is added in the cillin bottle containing 10mg lactose, put into lyophilization in vacuum freeze drier (see freeze-drying curve 3), the neogambogic acid lipidosome injection lyophilized injectable powder namely made.
Freeze-drying curve 3:
Operation programming rate time (h) temperature (DEG C)
(1) pre-freeze 3 room temperature is to-30 DEG C��-50 DEG C
(2) insulation 1.5-30 DEG C��-50 DEG C
(3) evacuation 0.5-30 DEG C��-50 DEG C
(4) intensification is warming up to-5 DEG C for 5-10 DEG C/h 6
(5) intensification 5-10 DEG C/h 4-5 DEG C is warming up to 0 DEG C
(6) intensification 5-10 DEG C/h 30 DEG C to 10 DEG C
(7) intensification 5-10 DEG C/h 310 DEG C to 25 DEG C
(8) insulation 225 DEG C
Embodiment 4:
Being dissolved in acetone by 15mg neogambogic acid and 120mg monostearate, 300mg lecithin dissolves with a small amount of ethanol, and two parts remix, and constitutes organic facies. 400mg poloxamer-188 and 200mg tween 80 are dissolved in water for injection, constitute aqueous phase. 70-80 DEG C of organic facies is slowly dropped into synthermal under (70-80 DEG C) aqueous phase in, constant temperature stirs 1 hour, take out and stir 1 hour in 0-2 DEG C of aqueous phase, obtain neogambogic acid lipidosome injection suspension, with the filtering with microporous membrane of 0.45 ��m, in the cillin bottle containing 10mg mannitol, add 1mL suspension, put into lyophilization in vacuum freeze drier (see freeze-drying curve 4), the neogambogic acid lipidosome injection lyophilized injectable powder namely made.
Freeze-drying curve 4:
Operation programming rate time (h) temperature (DEG C)
(1) pre-freeze 3 room temperature is to-30 DEG C��-50 DEG C
(2) insulation 1.5-30 DEG C��-50 DEG C
(3) evacuation 0.5-30 DEG C��-50 DEG C
(4) intensification is warming up to-5 DEG C for 5-10 DEG C/h 6
(5) intensification 5-10 DEG C/h 4-5 DEG C is warming up to 0 DEG C
(6) intensification 5-10 DEG C/h 30 DEG C to 10 DEG C
(7) intensification 5-10 DEG C/h 310 DEG C to 25 DEG C
(8) insulation 225 DEG C
Embodiment 5:
Being dissolved in acetone by 5mg neogambogic acid and 75mg monostearate, 150mg lecithin dissolves with a small amount of ethanol, and two parts remix, and constitutes organic facies. 600mg poloxamer-188 and 300mg tween 80 are dissolved in water for injection, constitute aqueous phase. 70-80 DEG C of organic facies is slowly dropped into synthermal under (70-80 DEG C) aqueous phase in, constant temperature stirs 1 hour, take out and stir 1 hour in 0-2 DEG C of aqueous phase, obtain neogambogic acid lipidosome injection suspension, with the filtering with microporous membrane of 0.45 ��m, in the cillin bottle containing 10mg mannitol, add 1mL suspension, put into lyophilization in vacuum freeze drier (see freeze-drying curve 5), the neogambogic acid lipidosome injection lyophilized injectable powder namely made.
Freeze-drying curve 5:
Operation programming rate time (h) temperature (DEG C)
(1) pre-freeze 3 room temperature is to-30 DEG C��-50 DEG C
(2) insulation 1.5-30 DEG C��-50 DEG C
(3) evacuation 0.5-30 DEG C��-50 DEG C
(4) intensification is warming up to-5 DEG C for 5-10 DEG C/h 6
(5) intensification 5-10 DEG C/h 4-5 DEG C is warming up to 0 DEG C
(6) intensification 5-10 DEG C/h 30 DEG C to 10 DEG C
(7) intensification 5-10 DEG C/h 310 DEG C to 25 DEG C
(8) insulation 225 DEG C
Embodiment 6:
The outward appearance of neogambogic acid lipidosome injection lyophilized powder and the investigation of color and luster:
Taking the neogambogic acid lipidosome injection freeze-dried powder preparation obtained in example 5, perusal is faint yellow uniformly, and in loose block, surface exquisiteness is bright and clean, has enough intensity.
Embodiment 7:
The investigation of the redispersibility of neogambogic acid lipidosome injection lyophilized powder:
Take the neogambogic acid lipidosome injection freeze-dried powder preparation obtained in example 5, add distilled water 1mL, gently jolting, be separated into uniform faint yellow neogambogic acid liposome colloid solution in 30s, it was shown that lyophilized preparation redispersibility is good.
Embodiment 8:
The investigation of the pH value of neogambogic acid lipidosome injection lyophilized powder:
Take the neogambogic acid lipidosome injection freeze-dried powder preparation obtained in example 5, after adding distilled water dispersion, measure pH value, three batch sample measurement results respectively 7.18,7.22,7.20, mean ph value is 7.20, compares pH value change little, lyophilized preparation acidity on the weak side before lyophilizing.
Claims (11)
1. a neogambogic acid lipidosome injection, it is characterized in that this neogambogic acid lipidosome injection is made up of neogambogic acid, phospholipid material, cholesterol, lipid adjuvant, organic acid or ammonium sulfate, sugar, buffer agent etc., it is optimum containing following component: neogambogic acid, hydrogenated soy phosphatidyl choline, cholesterol, Pegylation fat, organic acid or ammonium sulfate, sugar, buffer agent, and all the other form for water for injection.
2. neogambogic acid lipidosome injection according to claim 1, it is characterised in that wherein the weight percentage of each component is:
Neogambogic acid 0.01��10%
Phospholipid material 0.005��5%
Cholesterol 0.001��2%
Pegylation fat 0.005��1.5%
Organic acid or ammonium sulfate 0.0025��2.5%
Sugar 0.1��25%
Buffer agent 0.1��15%
All the other add to appropriate for water for injection composition.
3. the neogambogic acid lipidosome injection according to claim 1,2, it is characterised in that the preparation method of this neogambogic acid lipidosome injection has: injection method, film dispersion method, ultrasonic dispersion, reverse evaporation.
4. according to claim 1, neogambogic acid lipidosome injection described in 2, it is characterized in that described phospholipid material is selected from Ovum Gallus domesticus Flavus lecithin, hydrogenated yolk lecithin, soybean lecithin, hydrogenated soy phosphatidyl choline, DLPC, two myristoyl lecithin, DPPC, distearoylphosphatidylcholine, MPPC, PMPC, PSPC, SPPC, DOPC, two myristoyl phosphatidic acid, DPPA, two myristoyl phospholipid phthalein ethanolamine, two palmityl phospholipid phthalein ethanolamine, cephalin acyl serine, cranial nerve sphingomyelins, two palm fibres put phthalein sphingomyelin, distearyl sphingomyelin, one or more of DSPE, but it is not limited to this.
5. according to claim 1, neogambogic acid lipidosome injection described in 2, it is characterized in that described Pegylation fat is the stearate of 1000 ~ 10000Da selected from PEG molecular weight, PEG molecular weight is 1000 ~ 10000Da vitamin e succinate, methoxyl group PEG2000-distearoylphosphatidyl ethanol ammonium, cholesterol-PEG, dialycerides-PEG, DSPE multi-arm PEG or DSPE multi-arm PEG, PEG stearate and molecular weight are the mixture of the PEG of 200 ~ 10000Da, Myrj class, Brij class, PEG DSPE, PEG dipalmitoyl phosphatidyl choline, PEG DPPE, ganglioside, polyacrylamide, chitosan, Polyethylene Glycol gathers cetyl itrile group propionic ester, molecular weight is the PEG of 200 ~ 10000Da, one or more combination in any of PVP or PVA, but it is not limited to this.
6. neogambogic acid lipidosome injection according to claim 1, it is characterised in that sugar is selected from one or more of lactose, maltose, sucrose, glucose or trehalose, but is not limited to this.
7. the neogambogic acid lipidosome injection according to claim 1,2, it is characterised in that buffer agent is selected from histidine or glycine, but is not limited to this.
8. the neogambogic acid lipidosome injection according to claim 1 ~ 7, the preparation method of the neogambogic acid lipidosome injection described in any one, it is characterized in that the method comprises the following steps:
Neogambogic acid and the phospholipid material of claim 1, cholesterol, lipid adjuvant are added heat fusing or organic solvent dissolution, makes lipid soln;
Lipid soln is put the evaporation of rotary evaporator rotating thin film, makes lipid membrane;
By lipid membrane with the organic acid containing claim 1 or ammonium sulfate, sugar, aqueous solution of buffer agent hydration, concussion, or the lipid soln in (1) is directly mixed with aqueous solution concussion, make lipid aqueous dispersion;
Lipid aqueous dispersion is carried out emulsifying ultrasonic, homogeneous, microjet, press filtration process, thus preparing neogambogic acid liposome.
9. method according to claim 8, wherein said organic solvent is selected from one or more combination in any of dichloromethane, chloroform, acetone, isopropyl acetone, methanol, ethanol, ether, oxolane, dimethyl carbonate, the tert-butyl alcohol, chlorobutanol, ethyl acetate, propylene glycol, dimethyl sulfone, petroleum ether or isopropanol, but is not limited to this.
10. method according to claim 8, wherein add freeze drying protectant further to make lyophilized formulations to described prepared neogambogic acid liposome, the technique that obtained neogambogic acid liposome carries out frozen dried is: by 1 ~ 40%(weight ratio) freeze drying protectant be dissolved in the lipid aqueous dispersion of neogambogic acid liposome of the present invention, this freeze drying protectant is better to ensure formation lyophilized powder crystal formation, then it is divided in cillin bottle, it is placed in freezer dryer-45 DEG C of pre-freeze 2.5h, then it is refrigerated to-50 DEG C at 5 DEG C/h, maintain 10h, it is warming up to 0 DEG C again with 5 DEG C/h, maintain 8h, finally be warming up to 10 DEG C insulation 10h after outlet, jump a queue and seal.
11. method according to claim 10; wherein said freeze drying protectant is selected from one or more combination in any of trehalose, sucrose, mannitol, glucose, sodium chloride, lactose, sorbitol, xylitol, glucosan, Polyethylene Glycol, polyvinylpyrrolidone, dextran, glycerol or glycine, but is not limited to this.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410622327.2A CN105616354A (en) | 2014-11-07 | 2014-11-07 | Neogambogic acid liposome injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410622327.2A CN105616354A (en) | 2014-11-07 | 2014-11-07 | Neogambogic acid liposome injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105616354A true CN105616354A (en) | 2016-06-01 |
Family
ID=56031985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410622327.2A Pending CN105616354A (en) | 2014-11-07 | 2014-11-07 | Neogambogic acid liposome injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105616354A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107213452A (en) * | 2017-02-16 | 2017-09-29 | 徐州市中心医院 | A kind of preparation of liposome comprising MAP30 albumen and contain method |
| CN115869286A (en) * | 2022-11-10 | 2023-03-31 | 海南卓泰制药有限公司 | Amsacrine-containing encapsulating composition and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1718183A (en) * | 2005-04-22 | 2006-01-11 | 王效山 | Neo-garcinolic acid prepn. for injection use, prepn. method and use thereof |
| CN101879137A (en) * | 2010-06-11 | 2010-11-10 | 夏伦祝 | Method for preparing stealth liposome |
| CN101947204A (en) * | 2010-07-21 | 2011-01-19 | 彭代银 | Neo-gambogic acid SLN (solid lipid nanoparticle) and preparation method thereof |
| CN102091036A (en) * | 2011-01-10 | 2011-06-15 | 中国药科大学 | Compound liposome containing anti-tumor drugs and preparation method and application thereof |
| CN103315961A (en) * | 2012-03-20 | 2013-09-25 | 安徽中医学院 | Neogambogic acid self-microemulsifying preparation and preparation method thereof |
-
2014
- 2014-11-07 CN CN201410622327.2A patent/CN105616354A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1718183A (en) * | 2005-04-22 | 2006-01-11 | 王效山 | Neo-garcinolic acid prepn. for injection use, prepn. method and use thereof |
| CN101879137A (en) * | 2010-06-11 | 2010-11-10 | 夏伦祝 | Method for preparing stealth liposome |
| CN101947204A (en) * | 2010-07-21 | 2011-01-19 | 彭代银 | Neo-gambogic acid SLN (solid lipid nanoparticle) and preparation method thereof |
| CN102091036A (en) * | 2011-01-10 | 2011-06-15 | 中国药科大学 | Compound liposome containing anti-tumor drugs and preparation method and application thereof |
| CN103315961A (en) * | 2012-03-20 | 2013-09-25 | 安徽中医学院 | Neogambogic acid self-microemulsifying preparation and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 方玲等: ""新藤黄酸脂质体冻干粉的制备及其包封率测定"", 《安徽医药》 * |
| 陈延杰等: ""新藤黄酸固体脂质纳米粒的制备与质量评价"", 《中国药业》 * |
| 黄霞等: ""新藤黄酸纳米脂质载体制备及其药剂学性质研究"", 《中草药》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107213452A (en) * | 2017-02-16 | 2017-09-29 | 徐州市中心医院 | A kind of preparation of liposome comprising MAP30 albumen and contain method |
| CN115869286A (en) * | 2022-11-10 | 2023-03-31 | 海南卓泰制药有限公司 | Amsacrine-containing encapsulating composition and preparation method thereof |
| CN115869286B (en) * | 2022-11-10 | 2023-08-18 | 海南卓泰制药有限公司 | Encapsulation composition containing amsacrine and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11858958B2 (en) | Blank liposome with ginsenoside Rg3 or its analog as membrane materials and preparations and uses thereof | |
| US10639276B2 (en) | Liposomes with ginsenoside as membrane material and preparations and use thereof | |
| CA2704258C (en) | Novel thermosensitive liposomes containing therapeutic agents | |
| US9005655B2 (en) | Non-pegylated long-circulating liposomes | |
| JP2008534525A (en) | Nanomicelle formulation of anthracycline antitumor antibiotic encapsulated in polyethylene glycol derivative of phospholipid | |
| CN103479578B (en) | The Liposomal formulation of a kind of maleic acid Pixantrone and preparation technology thereof | |
| JP2009507049A (en) | Nanomicelle formulation of vinca alkaloid anticancer drug encapsulated in polyethylene glycol derivative of phospholipid | |
| CN102805730A (en) | Ceramide liposome and preparation method and application thereof | |
| CN101953792B (en) | Irinotecan nano circulating liposome and preparation method thereof | |
| CN112137958A (en) | Doxorubicin and immunologic adjuvant-containing combined drug liposome and preparation method thereof | |
| CN103622924B (en) | A kind of docetaxel liposome and preparation method thereof | |
| CN103622909A (en) | Cardiolipin-containing new liposome preparation, and its application in antitumor drugs | |
| CN106109415B (en) | A kind of load camptothecin antineoplastic agents liposome, preparation method and applications | |
| IL169364A (en) | Process for manufacturing non-pegylated liposomes involving aqueous hydration medium with sucrose | |
| CN102805729A (en) | Vinflunine liposome preparation and preparation method of vinflunine liposome preparation | |
| CN105616354A (en) | Neogambogic acid liposome injection and preparation method thereof | |
| CN110882218B (en) | Liposome composition and preparation and application thereof | |
| CN102085189B (en) | Docetaxel liposome sterile lyophilized preparation and preparation method thereof | |
| CN101849915A (en) | Vinorelbine stealth liposome freeze-dried powder injection and preparation method thereof | |
| CN102670509B (en) | Liposomal formulation containing slightly solubility camptothecine and preparation method thereof | |
| CN102188378A (en) | Preparation method of liposome for coating and carrying water soluble drugs | |
| CN1326525C (en) | 10-hydroxy camptothecin long cyclic liposome and its freeze aried preparation | |
| Zhu et al. | Preparation and studies of docetaxel proliposome | |
| CN101732232B (en) | Docetaxel nano-particle composition | |
| CN102138898A (en) | Nanometer liposome serving as antitumor medicament |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for 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: 20160601 |