CN103110931B - Prepare the method for sieve miaow ester peptidoliposome - Google Patents
Prepare the method for sieve miaow ester peptidoliposome Download PDFInfo
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- CN103110931B CN103110931B CN201310088137.2A CN201310088137A CN103110931B CN 103110931 B CN103110931 B CN 103110931B CN 201310088137 A CN201310088137 A CN 201310088137A CN 103110931 B CN103110931 B CN 103110931B
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- miaow ester
- sieve miaow
- peptidoliposome
- sieve
- liposome
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Abstract
The invention discloses a kind of method preparing sieve miaow ester peptidoliposome; take cholesterol as stabilizing agent; sucrose is freeze drying protectant; vitamin E is antioxidant; film dispersion method is adopted to prepare sieve miaow ester peptidoliposome; adopt high pressure homogenization method to make the particle diameter of liposome be less than 120nm, envelop rate is greater than 85% simultaneously.Sieve miaow ester peptidoliposome prepared by the method decreases the degraded of sieve miaow ester peptide, extends administration time, improves the compliance of patient, improve the targeting of sieve miaow ester peptide simultaneously, enhance its antitumor action.In formula, each composition is physiological compatibility material, and safety is high, can reduce the toxic and side effects of medicine.In addition, the preparation method technique that the present invention relates to is simple, with low cost, is applicable to suitability for industrialized production.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of method preparing sieve miaow ester peptidoliposome.
Background technology
Sieve miaow ester peptide (romidepsin); a kind of histon deacetylase (HDAC) (histone deacetylase; HDAC) inhibitor; it can cause histone to surpass acetylation; thus affect the gene expression of cell, in some cancerous cell, excessive histon deacetylase (HDAC) can suppress to regulate and control the gene activation of normal cell activity; therefore the activity reduction of this enzyme can activate these genes, and causes decreased growth or the stopping of cancerous cell.
Liposome is that every one deck is lipid bilayer, and vesicle inside is aqueous phase by amphiphilic species phospholipid and other amphoteric compounds as the multilamellar vesicle formed when cholesterol etc. is dispersed in aqueous phase.Liposome structure has the features such as applicable vivo degradation, avirulence and non-immunogenicity.Lot of experimental data proves that liposome has can improve drug therapeutic indices as pharmaceutical carrier, reduces drug toxicity and reduces the advantages such as drug side effect.And in recent years along with the development of biotechnology, liposomal preparation technique gradual perfection, liposome mechanism of action is illustrated further, and liposome more and more comes into one's own as the research of pharmaceutical carrier.
Sieve miaow ester peptide is a kind of peptides, easily degrade in vivo, thus affect its curative effect, and after making sieve miaow ester peptidoliposome, pharmaceutical pack is rolled in bilayer, can reduce the degraded of medicine, prolong drug circulation time in vivo, improve the targeting to tumor, thus improve its antitumor action.At present, domesticly in the research of sieve miaow ester peptide, blank is almost.
Summary of the invention
Technical problem to be solved by this invention overcomes above-mentioned deficiency existing in prior art, and provide a kind of method preparing sieve miaow ester peptidoliposome, to fill up domestic deficiency in the research of sieve miaow ester peptide formulations.
To achieve these goals, the present invention adopts following technical scheme:
Prepare a method for sieve miaow ester peptidoliposome, comprise following flow process:
(A) sieve miaow ester peptidoliposome formula
Described sieve miaow ester peptidoliposome formula comprises sieve miaow ester peptide, phospholipid, cholesterol, freeze drying protectant, antioxidant and buffer salt, and in formula, to be respectively sieve miaow ester peptide 2%-10%, phosphatidase 5 %-70%, cholesterol 1%-20%, freeze drying protectant 5%-25%, antioxidant 0.05%-5% and buffer salt appropriate for each components by weight;
(B) sieve miaow ester peptidoliposome preparation technology
Adopt film dispersion method to prepare sieve miaow ester peptidoliposome, concrete steps are:
(B1) phospholipid, cholesterol, antioxidant and sieve miaow ester peptide being dissolved in appropriate organic solvent and pouring in pear shape bottle, on Rotary Evaporators, organic solvent is removed in decompression, forms uniform thin film at bottle wall;
(B2) obtain adding the appropriate buffer salt containing freeze drying protectant in the pear shape bottle of homogeneous film in B1, aquation on a rotary evaporator, until eluted completely by dry film, and obtains homodisperse liposome;
(B3) liposome that B2 obtains is crossed high pressure homogenizer, obtain the liposome that mean diameter is less than 120nm;
(B4) lyophilizing after the liposome subpackage obtained by B3, every bottle containing sieve miaow ester peptide 10mg.
Further, described phospholipid is derive from the natural phospholipid in Semen sojae atricolor, egg yolk, animal viscera.
Further, described freeze drying protectant is one or more in mannitol, glucose, lactose, sucrose, maltose, trehalose.
Further, described antioxidant is one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, vitamin E, ascorbyl palmitate.
Further, described buffer salt is phosphate buffer, and its pH value is 6.8.
Further, the organic solvent in described (B1) step is the chloroform-methanol of 1: 1-1: 5.
Compared with prior art, The present invention reduces the degraded of sieve miaow ester peptide, extend administration time, improve the compliance of patient, improve the targeting of sieve miaow ester peptide simultaneously, enhance its antitumor action.In formula, each composition is physiological compatibility material, and safety is high, can reduce the toxic and side effects of medicine.In addition, the preparation method technique that the present invention relates to is simple, with low cost, is applicable to suitability for industrialized production.
Accompanying drawing explanation
Fig. 1 is the flow chart of sieve miaow ester peptidoliposome preparation technology of the present invention.
Detailed description of the invention
Below in conjunction with the drawings and specific embodiments, the invention will be further described.
The method that the present invention prepares sieve miaow ester peptidoliposome discloses sieve miaow ester peptidoliposome formula and sieve miaow ester peptidoliposome preparation technology, as follows:
(A) sieve miaow ester peptidoliposome formula
Described sieve miaow ester peptidoliposome formula comprises sieve miaow ester peptide, phospholipid, cholesterol, freeze drying protectant, antioxidant and buffer salt, and in formula, to be respectively sieve miaow ester peptide 2%-10%, phosphatidase 5 %-70%, cholesterol 1%-20%, freeze drying protectant 5%-25%, antioxidant 0.05%-5% and buffer salt appropriate for each components by weight.
Described phospholipid is derive from the natural phospholipid in Semen sojae atricolor, egg yolk, animal viscera.Described freeze drying protectant is one or more in mannitol, glucose, lactose, sucrose, maltose, trehalose.Described antioxidant is one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, vitamin E, ascorbyl palmitate.Described buffer salt is phosphate buffer, and its pH value is 6.8.
(B) sieve miaow ester peptidoliposome preparation technology
Adopt film dispersion method to prepare sieve miaow ester peptidoliposome, concrete steps are:
(B1) phospholipid, cholesterol, antioxidant and sieve miaow ester peptide being dissolved in appropriate organic solvent and pouring in pear shape bottle, on Rotary Evaporators, organic solvent is removed in decompression, forms uniform thin film at bottle wall.
(B2) obtain adding the appropriate buffer salt containing freeze drying protectant in the pear shape bottle of homogeneous film in B1, aquation on a rotary evaporator, until eluted completely by dry film, and obtains homodisperse liposome.
(B3) liposome that B2 obtains is crossed high pressure homogenizer, obtain the liposome that mean diameter is less than 120nm.
(B4) lyophilizing after the liposome subpackage obtained by B3, every bottle containing sieve miaow ester peptide 10mg.
Organic solvent in described (B1) step is the chloroform-methanol of 1: 1-1: 5.Certainly, the present invention is not limited to this, and in other embodiments, the organic solvent in described (B1) step also can be the organic solvent of other technical grade.
Embodiment 1: refer to Fig. 1, present invention is disclosed a kind of method preparing sieve miaow ester peptidoliposome, comprises following flow process:
Sieve miaow ester peptidoliposome prescription:
| Sieve miaow ester peptide | 0.3g |
| Injection fabaceous lecithin | 5g |
| Cholesterol | 1g |
| Sucrose | 2g |
| Vitamin E | 0.3g |
| PH value is 6.8 phosphate buffers | 100ml |
Sieve miaow ester peptidoliposome preparation technology: recipe quantity injection fabaceous lecithin, cholesterol, vitamin E and sieve miaow ester peptide are dissolved in the chloroform-methanol of 1: 1 and pour in pear shape bottle, on Rotary Evaporators, under 30rpm, 40 DEG C of water bath condition, organic solvent is removed in decompression, forms uniform thin film at bottle wall; Be in the phosphate buffer of 6.8 in 100ml pH value by recipe quantity sucrose dissolved, pour in pear shape bottle, in Rotary Evaporators, under 30rpm, 25 DEG C of water bath condition, aquation is complete; The liposome obtained is crossed high pressure homogenizer, pressure is 900bar, cycle-index is 3 times, obtain the liposome that mean diameter is 108nm; By lyophilizing after liposome subpackage, every bottle containing sieve miaow ester peptide 10mg.
Embodiment 2: refer to Fig. 1, present invention is disclosed a kind of method preparing sieve miaow ester peptidoliposome, comprises following flow process:
Sieve miaow ester peptidoliposome prescription:
| Sieve miaow ester peptide | 0.3g |
| Injection fabaceous lecithin | 5g |
| Cholesterol | 1g |
| Sucrose | 2g |
| Vitamin E | 0.3g |
| PH value is 6.8 phosphate buffers | 150ml |
Sieve miaow ester peptidoliposome preparation technology: recipe quantity injection fabaceous lecithin, cholesterol, vitamin E and sieve miaow ester peptide are dissolved in the chloroform-methanol of 1: 3 and pour in pear shape bottle, on Rotary Evaporators, under 40rpm, 45 DEG C of water bath condition, organic solvent is removed in decompression, forms uniform thin film at bottle wall; Be in the phosphate buffer of 6.8 in 150ml pH value by recipe quantity sucrose dissolved, pour in pear shape bottle, in Rotary Evaporators, under 40rpm, 35 DEG C of water bath condition, aquation is complete, the liposome obtained is crossed high pressure homogenizer, pressure is 700bar, cycle-index is 5 times, obtains the liposome that mean diameter is 95nm; By lyophilizing after liposome subpackage, every bottle containing sieve miaow ester peptide 10mg.
Embodiment 3: refer to Fig. 1, present invention is disclosed a kind of method preparing sieve miaow ester peptidoliposome, comprises following flow process:
Sieve miaow ester peptidoliposome prescription:
| Sieve miaow ester peptide | 0.3g |
| Injection fabaceous lecithin | 5g |
| Cholesterol | 1g |
| Sucrose | 2g |
| Vitamin E | 0.3g |
| PH value is 6.8 phosphate buffers | 200ml |
Sieve miaow ester peptidoliposome preparation technology: recipe quantity injection fabaceous lecithin, cholesterol, vitamin E and sieve miaow ester peptide are dissolved in the chloroform-methanol of 1: 5 and pour in pear shape bottle, on Rotary Evaporators, under 50rpm, 50 DEG C of water bath condition, organic solvent is removed in decompression, forms uniform thin film at bottle wall; Be in the phosphate buffer of 6.8 in 200ml pH value by recipe quantity sucrose dissolved, pour in pear shape bottle, in Rotary Evaporators, under 50rpm, 45 DEG C of water bath condition, aquation is complete, the liposome obtained is crossed high pressure homogenizer, pressure is 600bar, cycle-index is 7 times, obtains the liposome that mean diameter is 82nm; By lyophilizing after liposome subpackage, every bottle containing sieve miaow ester peptide 10mg.
The present invention reduces the degraded of sieve miaow ester peptide, extend administration time, improve the compliance of patient, improve the targeting of sieve miaow ester peptide simultaneously, enhance its antitumor action.In formula, each composition is physiological compatibility material, and safety is high, can reduce the toxic and side effects of medicine.In addition, the preparation method technique that the present invention relates to is simple, with low cost, is applicable to suitability for industrialized production.
More than in conjunction with most preferred embodiment, invention has been described, but the present invention is not limited to the embodiment of above announcement, and should contain various carry out according to essence of the present invention amendment, equivalent combinations.
Claims (1)
1. prepare a method for sieve miaow ester peptidoliposome, it is characterized in that, comprise following flow process:
(A) sieve miaow ester peptidoliposome formula
Described sieve miaow ester peptidoliposome formula comprises sieve miaow ester peptide, phospholipid, cholesterol, freeze drying protectant, antioxidant and buffer salt, and in formula, each components by weight is respectively sieve miaow ester peptide 0.3g, injection fabaceous lecithin 5g, cholesterol 1g, sucrose 2g, vitamin E 0.3g and pH value is 6.8 phosphate buffer 1 00ml;
(B) sieve miaow ester peptidoliposome preparation technology: recipe quantity injection fabaceous lecithin, cholesterol, vitamin E and sieve miaow ester peptide are dissolved in the chloroform-methanol of 1: 1 and pour in pear shape bottle, on Rotary Evaporators, under 30rpm, 40 DEG C of water bath condition, organic solvent is removed in decompression, forms uniform thin film at bottle wall; Be in the phosphate buffer of 6.8 in 100ml pH value by recipe quantity sucrose dissolved, pour in pear shape bottle, in Rotary Evaporators, under 30rpm, 25 DEG C of water bath condition, aquation is complete; The liposome obtained is crossed high pressure homogenizer, pressure is 900bar, cycle-index is 3 times, obtain the liposome that mean diameter is 108nm; By lyophilizing after liposome subpackage, every bottle containing sieve miaow ester peptide 10mg.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1660410A (en) * | 2004-12-24 | 2005-08-31 | 沈阳药科大学 | bFGF liposome and preparation method |
| CN101011357A (en) * | 2006-11-16 | 2007-08-08 | 西安力邦医药科技有限责任公司 | Process for preparing Paclitaxel liposome preparation |
| CN101687010A (en) * | 2006-12-29 | 2010-03-31 | 格洛斯特制药公司 | Romidepsin preparation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1530465B2 (en) * | 2002-06-26 | 2015-12-16 | MediGene AG | Method of producing a cationic liposomal preparation comprising a lipophilic compound |
| IT1404011B1 (en) * | 2010-12-03 | 2013-11-08 | Uni Degli Studi Magna Graecia Di Catanzaro | CONJUGATED NANOVECTOR WITH TSH FOR TREATMENT OF THYROID CANCER |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1660410A (en) * | 2004-12-24 | 2005-08-31 | 沈阳药科大学 | bFGF liposome and preparation method |
| CN101011357A (en) * | 2006-11-16 | 2007-08-08 | 西安力邦医药科技有限责任公司 | Process for preparing Paclitaxel liposome preparation |
| CN101687010A (en) * | 2006-12-29 | 2010-03-31 | 格洛斯特制药公司 | Romidepsin preparation |
Non-Patent Citations (2)
| Title |
|---|
| 抗肿瘤药罗米地辛的药理与临床研究;杜燕京等;《中国新药杂志》;20111231;第2卷(第7期);第573-576页 * |
| 薄膜分散法制备 RGD脂质体;齐滨等;《长春中医药大学学报》;20080430;第24卷(第2期);第155页左栏第一段、右栏最后一段和第156页左栏第一段 * |
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Effective date of registration: 20200401 Address after: 510670 room B03, building 301, No.1, Nanxiang Second Road, Huangpu District, Guangzhou (Guangzhou high tech Industrial Development Zone), Guangzhou City, Guangdong Province Patentee after: Guangzhou maikaian Biomedical Research Institute Co., Ltd Address before: 510000 Guangdong city of Guangzhou province Luogang District spire J Road No. 1 the first floor of the building by 1. Patentee before: GUANGZHOU MEDCAN PHARMATECH Ltd. |
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