CN103585466A - Sapodilla saponin composite precursor liposome and preparation method thereof - Google Patents

Sapodilla saponin composite precursor liposome and preparation method thereof Download PDF

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CN103585466A
CN103585466A CN201310588212.1A CN201310588212A CN103585466A CN 103585466 A CN103585466 A CN 103585466A CN 201310588212 A CN201310588212 A CN 201310588212A CN 103585466 A CN103585466 A CN 103585466A
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saponin
herba herminii
composite precursor
herminii saponin
liposome
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CN103585466B (en
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滕利荣
何妍茜
杨爽
孟庆繁
逯家辉
刘艳
王贞佐
程瑛琨
杨雪薇
权宇彤
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Jilin University
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Abstract

The invention discloses a sapodilla saponin composite precursor liposome and a preparation method thereof. The sapodilla saponin composite precursor liposome is prepared by sapodilla saponin, a pear peel extract, phospholipid, cholesterol, a surface active agent and a water-soluble carrier according to a certain method. The sapodilla saponin composite precursor liposome of the invention is ease to prepare, so that the scale production can be achieved; as the sapodilla saponin composite precursor liposome is a liquid or a dry solid particle material with an excellent flowing performance, easy storage is achieved before hydration. The material is added with pharmaceutical acceptable auxiliaries to prepare any oral liquid or external dosage forms in the pharmacy; the product quality is preferably guaranteed. The sapodilla saponin composite precursor liposome has the advantages of scientific formula, obvious cooperative effect between the sapodilla saponin and the pear peel extract, reasonable preparation technique, no damage on effective components in raw materials of traditional Chinese medicines, no toxic and side effect, no addiction and no drug resistance.

Description

Herba Herminii saponin's composite precursor liposome and preparation method
Technical field
The present invention is a kind of Herba Herminii saponin's composite precursor liposome and preparation method, with and at supplementing QI and nourishing YIN, and the effect in antitumor field, belongs to Chinese medicine preparation technical field.
Background technology
During the nearly last ten years, Herba Herminii saponin is mainly used in the aspects such as prevention or treatment cardiovascular and cerebrovascular vessel and prophylaxis of tumours, but its dosage form is mainly with general formulation or injection, general formulation is lower to Herba Herminii saponin's availability, and injection is all more complicated in production and use, therefore prepare a kind of taking convenience, and can medicine biology degree to obtain dosage form very necessary.The generation of taking advantage of a situation of oral liposome, adopts liposome to form drug effective region or monomer again, due to adding of phospholipid wherein, can extend its release time in vivo, increases the bioavailability of medicine.Prepare oral liposome, method be first prepared into recycle after liposome liposome powder in addition adjuvant make various dosage forms.
And Pericarpium Pyri extract has clearing away heart-fire and moistening the lung, pathogenic fire reducing promotes the production of body fluid, the effect of life lengthening; At < < book on Chinese herbal medicine new > > again: the saying of " promoting the production of body fluid to quench thirst, relieving restlessness is dried for clearing heart fire, nourishing kidney tonifying YIN ".Task of the present invention is to utilize Herba Herminii saponin and Pericarpium Pyri extract to have obvious synergism, prepare a kind of can have higher curative effect for the preparation of supplementing QI and nourishing YIN and anti-tumor drug.
Summary of the invention
The invention provides a kind of Herba Herminii saponin's composite precursor liposome, for supplementing QI and nourishing YIN and antineoplastic medical usage.
The present invention also provides the preparation method of Herba Herminii saponin's composite precursor liposome, is applicable to suitability for industrialized production.
The present invention open Herba Herminii saponin's composite precursor liposome, is characterized in that by following raw materials by weight portion than making:
Herba Herminii saponin 1, Pericarpium Pyri extract 0.01 ~ 1, phosphatidase 10 .2 ~ 5, cholesterol 0 ~ 0.5, surfactant 0 ~ 0.5, water-solubility carrier 0.2 ~ 20.
The preparation method of described Pericarpium Pyri extract is as follows:
Get 1 part of dry Pericarpium Pyri and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 4 ~ 8 (mass/volume) times of total medical material amount, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into 10% ~ 20% of original volume, by the volume ratio of supernatant/95% ethanol=1/ (1 ~ 3), adds 95% ethanol, and precipitation, gets supernatant, and after concentration and recovery ethanol, spraying is dried to obtain extract dry powder.
The preparation method of Herba Herminii saponin's composite precursor liposome of the present invention, comprises the following steps:
(1) described water-solubility carrier, phospholipid, surfactant, cholesterol, Pericarpium Pyri extract, Herba Herminii saponin are made to solution, mix, filter;
(2) dry, sieve, both obtained Herba Herminii saponin's composite precursor liposome.
The preparation method of Herba Herminii saponin's composite precursor liposome of the present invention, also can realize by following steps:
(1) described water-solubility carrier, Pericarpium Pyri extract and Herba Herminii saponin are made to solution, mix, be placed in flask, rotary evaporation, flask immerses in 30 ~ 70 ℃ of water-baths;
(2) phospholipid, cholesterol, surfactant dissolves, in dehydrated alcohol, are made solution; Add gradually in the powder bed of rotation, vacuum decompression is evaporated to solvent and is substantially evaporated completely;
(3) by powder for drying, sieve, obtain Herba Herminii saponin's composite precursor liposome.
Or
(1) get Herba Herminii saponin and Pericarpium Pyri extract and add water and be prepared into solution, phospholipid, surfactant, cholesterol are dissolved in dehydrated alcohol;
(2) ethanol solution is injected to Herba Herminii saponin's aqueous solution, make liposome solutions;
(3) water-solubility carrier is added in liposome solutions, spraying is dried or lyophilization, obtains Herba Herminii saponin's composite precursor liposome.
Herba Herminii saponin's composite precursor liposome adds after medically acceptable adjuvant, makes any oral or exterior-applied formulation in pharmaceutics.
The application of Herba Herminii saponin's composite precursor liposome in supplementing QI and nourishing YIN and antitumor field.
1, prepare oral formulations: the pharmaceutical composition of Herba Herminii saponin's pro-liposome powder being made to the different dosage form that is applicable to use clinically, suitably add as required again the excipient such as diluent, adsorbent, dispersant, wetting agent, binding agent, disintegrating agent, lubricant, absorption enhancer, solubilizing agent, antioxidant, surfactant, correctives, coloring agent, can be made into the dosage form such as tablet, capsule, powder, granule that is suitable for oral administration.
2, prepare external preparation: the pharmaceutical composition of Herba Herminii saponin's pro-liposome powder being made to the different dosage form that is applicable to use clinically, suitably add as required again additives or the substrate such as solubilizing agent, absorption enhancer, antiseptic, antioxidant, propellant, cosolvent, wetting agent, emulsifying agent, stabilizing agent, correctives, surfactant, can be made into the dosage form such as cataplasma, spray, aerosol, cream, ointment that is suitable for topical administration.
Good effect of the present invention is: utilize Herba Herminii saponin and Pericarpium Pyri extract to have obvious synergism, and compatibility science, preparation technology is reasonable, does not destroy the effective ingredient of raw material of Chinese medicine, has no side effect, and without addiction, has no drug resistance.
The specific embodiment
Below in conjunction with embodiment, the present invention is further explained.Should be understood that, following examples are only for explaining the present invention, rather than limit the scope of the invention.
embodiment 1
The present embodiment is Herba Herminii saponin's composite precursor liposome that Herba Herminii saponin, Pericarpium Pyri extract, phospholipid (Ovum Gallus domesticus Flavus lecithin), surfactant (NaTDC), cholesterol and water-solubility carrier (mannitol) are prepared into.
Get the dry Pericarpium Pyri of 200g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 1000mL times, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into 100mL, adds 95% ethanol 200mL, and precipitation, gets supernatant, and after concentration and recovery ethanol, spraying is dried to obtain extract dry powder.
Get Herba Herminii saponin 1g, Pericarpium Pyri extract dry powder 0.5g, Ovum Gallus domesticus Flavus lecithin 5g, NaTDC 0.25g, cholesterol 0.1g, mannitol 20g are dissolved in 30% alcoholic solution, mix, and filter, dry, sieve, both Herba Herminii saponin's composite precursor liposome.
embodiment 2
The present embodiment is Herba Herminii saponin's pro-liposome that Herba Herminii saponin, phospholipid (soybean lecithin), Pericarpium Pyri extract, surfactant (Tween 80), cholesterol and water-solubility carrier (fructose) are prepared into.
Get the dry Pericarpium Pyri of 100g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 500mL, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into the 50mL of original volume, adds 95% ethanol 100mL, and precipitation, gets supernatant, the dry extract dry powder that to obtain of spraying after concentration and recovery ethanol.
Fructose 10g, Pericarpium Pyri extract 1g and Herba Herminii saponin 2g are made to solution, mix, be placed in flask, rotary evaporation, flask immerses in 60 ℃ of water-baths; Soybean lecithin 5g, cholesterol 1g, Tween 80 0.2g are dissolved in 20mL dehydrated alcohol, make solution; Add gradually in the powder bed of rotation; Vacuum decompression is evaporated to solvent and is substantially evaporated completely; By powder for drying, sieve, obtain Herba Herminii saponin's composite precursor liposome.
embodiment 3
The present embodiment is Herba Herminii saponin's pro-liposome that Herba Herminii saponin, phospholipid (soybean lecithin), Pericarpium Pyri extract, surfactant (NaTDC), cholesterol and water-solubility carrier (Macrogol 2000) are prepared into.
Get the dry Pericarpium Pyri of 100g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 400mL, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into the 80mL of original volume, adds 95% ethanol 200mL, and precipitation, gets supernatant, the dry extract dry powder that to obtain of spraying after concentration and recovery ethanol.
Get Herba Herminii saponin 1g and Pericarpium Pyri extract 1g and add water and be prepared into solution, soybean lecithin 2g, NaTDC 0.2g, cholesterol 0.2g are dissolved in dehydrated alcohol; Ethanol solution is injected to Herba Herminii saponin's aqueous solution, make liposome solutions; Water-solubility carrier Macrogol 2000 15g is added in liposome solutions, and spraying is dry, obtains Herba Herminii saponin's composite precursor liposome.
embodiment 4
The present embodiment is Herba Herminii saponin's composite precursor liposome that Herba Herminii saponin, Pericarpium Pyri extract, phospholipid (soybean lecithin), surfactant (NaTDC), cholesterol and water-solubility carrier (lactose) are prepared into.
Get the dry Pericarpium Pyri of 200g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 1000mL times, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into 150mL, adds 95% ethanol 200mL, and precipitation, gets supernatant, and after concentration and recovery ethanol, spraying is dried to obtain extract dry powder.
Get Herba Herminii saponin 1g, Pericarpium Pyri extract dry powder 0.5g, soybean lecithin 5g, NaTDC 0.25g, cholesterol 0.1g, lactose 20g are dissolved in 60% alcoholic solution, mix, and filter, dry, sieve, both Herba Herminii saponin's composite precursor liposome.
embodiment 5
The present embodiment is Herba Herminii saponin's pro-liposome that Herba Herminii saponin, phospholipid (Ovum Gallus domesticus Flavus lecithin), Pericarpium Pyri extract, surfactant (NaTDC), cholesterol and water-solubility carrier (mannitol) are prepared into.
Get the dry Pericarpium Pyri of 100g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 500mL, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into the 100mL of original volume, adds 95% ethanol 300mL, and precipitation, gets supernatant, the dry extract dry powder that to obtain of spraying after concentration and recovery ethanol.
Mannitol 10g, Pericarpium Pyri extract 1g and Herba Herminii saponin 2g are made to solution, mix, be placed in flask, rotary evaporation, flask immerses in 50 ℃ of water-baths; Ovum Gallus domesticus Flavus lecithin 5g, cholesterol 1g, NaTDC 0.1g are dissolved in dehydrated alcohol, make solution; Add gradually in the powder bed of rotation; Vacuum decompression is evaporated to solvent and is substantially evaporated completely; By powder for drying, sieve, obtain Herba Herminii saponin's composite precursor liposome.
embodiment 6
The present embodiment is Herba Herminii saponin's pro-liposome that Herba Herminii saponin, phospholipid (soybean lecithin), Pericarpium Pyri extract, surfactant (NaTDC), cholesterol and water-solubility carrier (Macrogol 2000) are prepared into.
Get the dry Pericarpium Pyri of 100g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 400mL, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into the 50mL of original volume, adds 95% ethanol 150mL, and precipitation, gets supernatant, the dry extract dry powder that to obtain of spraying after concentration and recovery ethanol.
Get Herba Herminii saponin 1g and Pericarpium Pyri extract 1g and add water and be prepared into solution, soybean lecithin 2g, NaTDC 0.1g, cholesterol 0.1g are dissolved in dehydrated alcohol; Ethanol solution is injected to Herba Herminii saponin's aqueous solution, make liposome solutions; Water-solubility carrier Macrogol 2000 15g is added in liposome solutions, and lyophilization, obtains Herba Herminii saponin's composite precursor liposome.
embodiment 7
The present embodiment is Herba Herminii saponin's pro-liposome that Herba Herminii saponin, phospholipid (soybean lecithin), Pericarpium Pyri extract, cholesterol and water-solubility carrier (mannitol) are prepared into.
Get the dry Pericarpium Pyri of 100g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 400mL, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into the 50mL of original volume, adds 95% ethanol 150mL, and precipitation, gets supernatant, the dry extract dry powder that to obtain of spraying after concentration and recovery ethanol.
Get Herba Herminii saponin 1g and Pericarpium Pyri extract 1g and add water and be prepared into solution, soybean lecithin 2g, cholesterol 0.1g are dissolved in dehydrated alcohol; Ethanol solution is injected to Herba Herminii saponin's aqueous solution, make liposome solutions; Water-solubility carrier mannitol 15g is added in liposome solutions, and lyophilization, obtains Herba Herminii saponin's composite precursor liposome.
embodiment 8
The present embodiment is Herba Herminii saponin's pro-liposome that Herba Herminii saponin, phospholipid (Ovum Gallus domesticus Flavus lecithin), Pericarpium Pyri extract, surfactant (span) and water-solubility carrier (mannitol) are prepared into.
Get the dry Pericarpium Pyri of 100g and decoct with water extraction 3 times, the quantity of solvent at every turn adding is 400mL, and extraction time is 1 hour; Merge extractive liquid,, is concentrated into the 50mL of original volume, adds 95% ethanol 150mL, and precipitation, gets supernatant, the dry extract dry powder that to obtain of spraying after concentration and recovery ethanol.
Get Herba Herminii saponin 1g and Pericarpium Pyri extract 1g and add water and be prepared into solution, Ovum Gallus domesticus Flavus lecithin 2g, span 0.1g are dissolved in dehydrated alcohol; Ethanol solution is injected to Herba Herminii saponin's aqueous solution, make liposome solutions; Water-solubility carrier mannitol 15g is added in liposome solutions, and spraying is dry, obtains Herba Herminii saponin's composite precursor liposome.
embodiment 9
The present embodiment is Herba Herminii saponin's composite precursor liposome tablet.
Herba Herminii saponin's pro-liposome powder (embodiment 1): 1kg, starch, dextrin mixture and hypromellose (2/2/1): 1kg;
Get Herba Herminii saponin's pro-liposome powder, the adjuvant of weight such as add as excipient, mix homogeneously, obtains mixed-powder; Add 95% ethanol to make soft material, 16-20 mesh sieve is granulated, dry 30 minutes of 70 ~ 80 ℃ of wet granulars, 16-20 mesh sieve granulate, tabletting and get final product.Sundry item should meet 2010 editions tablet project relevant requirements of Pharmacopoeia of People's Republic of China.
following experiment has shown the beneficial effect of Radix Ginseng fruit saponin pro-liposome of the present invention:
1 experiment material and method
1.1 experiment material
Laboratory animal, SD male rat body weight 300 ± 10g, purchased from Jilin University's medical board Experimental Animal Center, in 20 ± 1 ℃ of room temperatures, humidity 55 ± 10%, in rate of ventilation 20 ± 2 times/time, raises 1 week under 12 hours light and shade cycling conditions, for experiment.Between preparation feeding period, feeding solid feed (purchased from Jilin University's medical board Experimental Animal Center), water freely absorbs.Pericarpium Pyri extract is prepared voluntarily by this laboratory, and Herba Herminii saponin's composite precursor liposome (as embodiment 1, embodiment 2, embodiment 3) is prepared voluntarily by this laboratory.
1.2 experimental technique
1.2.1 medication and sample collecting
Select qualified SD male rat, be divided at random 6 groups; The Herba Herminii saponin and Pericarpium Pyri extract mixtures (C) and the 3 groups of Herba Herminii saponin's composite precursor liposomees (embodiment 1, embodiment 2, embodiment 3) that gavage respectively Herba Herminii saponin (A), Pericarpium Pyri extract (B), weight ratio 1:1, dosage is 200mg/kg.After administration, 10min, 25min, 40min, 75min, 120min, 180min, 240min, 300min and 600min get blood through eye socket venous plexus, put in the plastic centrifuge tube of oiling heparin, the centrifugal 10min of 10000rpm, separated plasma ,-20 ℃ of Refrigerator stores are until analyze.
1.2.2 the preparation of blood serum sample
Get serum 200 μ L, add methanol ImL, vortex vibration 1min, 5000rmin -1centrifugal l0min, draws supernatant, and 40 ℃ of water-bath N2 dry up, and residue adds 200 μ L methanol, vortex 1min, and ultrasonic 5min fully dissolves residue, obtains need testing solution.
2 experimental results
The pharmacokinetic parameter comparative result of the Herba Herminii saponin of Herba Herminii saponin (A), Pericarpium Pyri extract (B), weight ratio 1:1 and Pericarpium Pyri extract mixtures (C) and 3 groups of Herba Herminii saponin's composite precursor liposomees (embodiment 1, embodiment 2, embodiment 3) is as shown in the table
Table 1 pharmacokinetic parameter comparison (n=6)
Figure 2013105882121100002DEST_PATH_IMAGE001
AUC value is one of important parameter of evaluating drug bioavailability, and this experimental studies results shows, under the drug-time curve of Herba Herminii saponin's group (A), area is 12183.29 ± 23 ngminmL -1; Under the drug-time curve of Pericarpium Pyri extract (B), area is 11159.35 ± 123 ngminmL -1; Under the Herba Herminii saponin of weight ratio 1:1 and Pericarpium Pyri extract mixtures (C) drug-time curve, area is 16028 ± 221 ngminmL -1; Long-pending 19235 ± 233,17235 ± 183,22235 ± 296 ngminmL that are respectively below 3 groups of Herba Herminii saponin's composite precursor liposomees (embodiment 1, embodiment 2, embodiment 3) drug-time curve -1.
The Evaluation On The Bioavailability result of study of Herba Herminii saponin (A), Pericarpium Pyri extract (B), Herba Herminii saponin and Pericarpium Pyri extract mixtures (C) and 3 groups of Herba Herminii saponin's composite precursor liposomees (embodiment 1, embodiment 2, embodiment 3) shows, Herba Herminii saponin and Pericarpium Pyri extract have significant synergism; On this basis, be prepared as after pro-liposome, extended soak time in its body, raising to a certain degree Herba Herminii saponin's bioavailability, comparatively remarkable to the improvement of drug bioavailability, reached preparation object.

Claims (5)

1. Herba Herminii saponin's composite precursor liposome, is characterized in that by following raw materials by weight portion than making:
Herba Herminii saponin 1, Pericarpium Pyri extract 0.01 ~ 1, phosphatidase 10 .2 ~ 5, cholesterol 0 ~ 0.5,
Surfactant 0 ~ 0.5, water-solubility carrier, 0.2 ~ 20.
2. the preparation method of Herba Herminii saponin's composite precursor liposome according to claim 1, the sequential steps comprising is:
1) described water-solubility carrier, phospholipid, surfactant, cholesterol, Pericarpium Pyri extract, Herba Herminii saponin are made to solution, mix, filter;
2) dry, sieve, both obtained Herba Herminii saponin's composite precursor liposome.
3. the preparation method of Herba Herminii saponin's composite precursor liposome according to claim 1, the sequential steps comprising is:
1) described water-solubility carrier, Pericarpium Pyri extract and Herba Herminii saponin are made to solution, mix, be placed in flask, rotary evaporation, flask immerses in 30 ~ 70 ℃ of water-baths;
2) phospholipid, cholesterol, surfactant dissolves, in dehydrated alcohol, are made solution; Add gradually in the powder bed of rotation, vacuum decompression is evaporated to solvent and is substantially evaporated completely;
3) by powder for drying, sieve, obtain Herba Herminii saponin's composite precursor liposome.
4. the preparation method of Herba Herminii saponin's composite precursor liposome according to claim 1, the sequential steps comprising is:
(1) get Herba Herminii saponin and Pericarpium Pyri extract and add water and be prepared into solution, phospholipid, surfactant, cholesterol are dissolved in dehydrated alcohol;
(2) ethanol solution is injected to Herba Herminii saponin's aqueous solution, make liposome solutions;
(3) water-solubility carrier is added in liposome solutions, spraying is dried or lyophilization, obtains Herba Herminii saponin's composite precursor liposome.
5. Herba Herminii saponin's composite precursor liposome according to claim 1 adds after medically acceptable adjuvant, makes any oral or exterior-applied formulation in pharmaceutics.
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