CN105311637A - Pharmaceutical composition containing herpetin - Google Patents
Pharmaceutical composition containing herpetin Download PDFInfo
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- CN105311637A CN105311637A CN201410378372.8A CN201410378372A CN105311637A CN 105311637 A CN105311637 A CN 105311637A CN 201410378372 A CN201410378372 A CN 201410378372A CN 105311637 A CN105311637 A CN 105311637A
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Abstract
The invention provides a pharmaceutical composition with a function of completely improving bioavailability and curative effects of herpetin. The pharmaceutical composition comprises the herpetin and phosphatidyl ethanolamine. The pharmaceutical composition has functions of liver injury prevention, liver protection, transaminase reduction and hepatitis B virus replication inhibition and can be used for treatment of liver injury and hepatitis B.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of pharmaceutical composition containing Bolengsu and preparation method thereof.
Background technology
Bolengsu (Herpetin) is the active monomer component separated from the lignanoid Herpetospermum pedunculosum (HerPetospermumcaudigerumWall.), chemical constitution is: 3-benzofuran first hydroxyl-2,3-dihydro-2-(4-hydroxy-3-methoxy) benzene-4-methoxyl group-6-(2-(3-hydroxyl-4-methoxyl group) benzene-3-first hydroxy-2-methyl oxolane), chemical constitution See Figure.
Pharmacological activity research shows, it has the effect of anti-liver injury, the liver protecting and ALT lowering, suppression hepatitis B replication, can be used for the treatment of hepatic injury, hepatitis B.But due to the chemical property of its indissoluble, present stage is not widely used in clinical.Liver energy drop pill is made in its total lignans position by prior art, but drop pill complicated component, and curative effect is not obvious, and the complex process of preparation, be difficult to the needs adapting to market.
The present inventor also once utilized cholesterol, soybean phospholipid to adopt film dispersion method to prepare HPT liposome solutions early stage, but in follow-up exploration, find that the liposome encapsulation obtained not is very high, and liposome easily breaks, and is not easy to preserve, and affects the treatment.Clinical at present, be badly in need of the pharmaceutical preparation of the suitable Bolengsu Clinical practice of exploitation.
The present inventor have been surprisingly found that, the pharmaceutical composition of Bolengsu and PHOSPHATIDYL ETHANOLAMINE can improve the bioavailability of Bolengsu, curative effect and stability thereof significantly.
Summary of the invention
The object of this invention is to provide and a kind ofly significantly improve the bioavailability of Bolengsu and the pharmaceutical composition of curative effect, described compositions is containing Bolengsu and PHOSPHATIDYL ETHANOLAMINE.
PHOSPHATIDYL ETHANOLAMINE is the good non-toxic of a kind of toleration
surfactant, can obtain in vivo
metabolism.The present inventor's research is surprised to find that, PHOSPHATIDYL ETHANOLAMINE can with the coupling of Bolengsu chemical constitution phase, promote its metabolic adsorption in vivo, be beneficial to and improve the bioavailability of Bolengsu.
The object of this invention is to provide a kind of pharmaceutically acceptable pharmaceutical preparation containing Bolengsu and acyl ethanolamine being suitable for Clinical practice.
Pharmaceutical preparation of the present invention, based on parts by weight, containing Bolengsu 1-10 part and acyl ethanolamine 10-100 part and other pharmaceutically acceptable excipient.
Pharmaceutically acceptable pharmaceutical preparation of the present invention is preferably from oral formulations, Parenteral formulations, slow releasing preparation, controlled release preparation etc.
Pharmaceutically acceptable pharmaceutical preparation of the present invention can be selected from: solid preparation, liquid preparation etc.
As concrete example, described preparation is selected from tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, sucks agent, granule, electuary, pill, micelle, powder, unguentum, sublimed preparation, microemulsion, suspensoid, powder, liposome, solution, injection, suppository, microcapsule, ointment, plaster, cream, spray, drop, patch; Preferred oral dosage form, as: capsule, tablet, oral liquid, granule, pill, powder, sublimed preparation, unguentum etc.
Pharmaceutical preparation of the present invention, except Bolengsu and acyl ethanol, also can add other pharmaceutically acceptable excipient, such as binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, flavoring agent, wetting agent, slow releasing agent, pH adjusting agent, antioxidant, coating solution etc.
As liquid preparation, suitable excipient comprises
antiseptic,
antioxidant,
correctives, aromatic,
cosolvent,
emulsifying agent,
solubilizing agent, osmotic pressure regulator,
coloring agentdeng.
Further preferably, as controlled release preparation, such as Liposomal formulation, suitable excipient is selected from cholesterol.
As one of specific embodiments, the combination of Bolengsu of the present invention and acyl ethanol can be made into Liposomal formulation.
The object of this invention is to provide a kind of solid preparation, comprise based on 1-5 part Bolengsu of parts by weight, 10-50 part PHOSPHATIDYL ETHANOLAMINE, filler 10-100 part, disintegrating agent 10-100 part and appropriate 75% ethanol; Preferably comprise based on 1 part of Bolengsu of parts by weight, 10 parts of PHOSPHATIDYL ETHANOLAMINE, starch 25 parts, carmethose 18 parts, appropriate 75% ethanol.
Described filler can be selected from starch, pregelatinized Starch, microcrystalline Cellulose, optimization microcrystalline Cellulose, Powderd cellulose, saccharide, sugar derivatives and combination thereof.
Described disintegrating agent can be selected from carboxymethylstach sodium, polyvinylpolypyrrolidone, primojel, L-hydroxypropyl cellulose, sodium carboxymethyl cellulose and combination thereof.
The object of this invention is to provide a kind of liquid preparation, comprise based on 0.05-0.5 part Bolengsu of parts by weight, 0.5-2 part PHOSPHATIDYL ETHANOLAMINE, 1-10 part glycerol, 1-5 part glucose sugar and appropriate sodium dihydrogen phosphate; Preferably comprise based on 0.08 part of Bolengsu of parts by weight, 1 part of PHOSPHATIDYL ETHANOLAMINE, 5 parts of glycerol, 2.5 portions of glucose sugar and appropriate sodium dihydrogen phosphate.
The object of this invention is to provide a kind of Liposomal formulation, comprise based on parts by weight, 0.1-1 part Bolengsu, 5-15 part PHOSPHATIDYL ETHANOLAMINE, 1-5 part cholesterol; Preferably comprise based on 0.32 part of Bolengsu of parts by weight, 10.1 parts of PHOSPHATIDYL ETHANOLAMINE, 2.52 parts of cholesterol.
A further object of the present invention is to provide the solid preparation of the Liposomal formulation of Bolengsu and PHOSPHATIDYL ETHANOLAMINE as freeze-dried powder, comprises 50-200 part Bolengsu liposome, 5-25 part sucrose, 5-25 part lactose based on parts by weight; Preferably comprise based on 125 parts of Bolengsu liposomees of parts by weight, 6.25 parts of sucrose, 6.25 parts of lactose.
To achieve these goals, invention further provides the method for the pharmaceutical preparation preparing compositions of the present invention.
One of specific embodiments, provides a kind of method preparing the tablet of Bolengsu and PHOSPHATIDYL ETHANOLAMINE, it is characterized in that comprising the following steps:
1. Bolengsu, PHOSPHATIDYL ETHANOLAMINE are dissolved in 75% ethanol, for subsequent use;
2. filler, disintegrating agent are pulverized, cross 80 mesh sieves, mix homogeneously, for subsequent use;
3. the adjuvant in is 2. added the ethanol 1., use fluidized bed granulation, until without residual powder, drying obtains primary granule.
4. the primary granule tabletting will obtained in 3., obtains tablet.
One of specific embodiments, provides a kind of method preparing liquid preparation containing Bolengsu and PHOSPHATIDYL ETHANOLAMINE, it is characterized in that comprising the following steps:
1. Bolengsu, PHOSPHATIDYL ETHANOLAMINE are dissolved in glycerol, for subsequent use;
2. by obtain 1. in solution and sodium dihydrogen phosphate add water for injection, regulate PH to 7.0;
3. the solution obtained in is 2. added glucose, regulate osmotic pressure, sterilizing, namely obtains liquid preparation.
One of specific embodiments, provide a kind of prepare liposome method, it is characterized in that comprising the following steps:
1. take Bolengsu, PHOSPHATIDYL ETHANOLAMINE and cholesterol, be dissolved in q. s. methylene chloride.
2. the mixed solution 1. obtained is proceeded in ground round-bottomed flask, at 20-40 DEG C of water-bath decompression removing dichloromethane, make filmogen bottom bottle, form an even lipid membrane;
3. the even lipid membrane 2. obtained is added appropriate span80 aqueous solution, at 30-60 DEG C, Rotary Evaporators rotates and washes film 20-40min.
4. by the lipid membrane eluting 3. obtained and hydration becomes liposome just suspension, water bath sonicator, crosses 0.22 μm of filter membrane, obtains Bolengsu liposome.
One of specific embodiments, provides a kind of method preparing liposome freeze-drying powder injection, is characterised in that and comprises the following steps:
1. Bolengsu liposome the present invention prepared adds sucrose and lactose, stirs and makes it all dissolve, be dispensed in the bottle of Xining;
2. freezing 2-5 hour in the refrigerator Xining bottle that suspension is housed 1. obtained being put into-20 to-40 DEG C, proceeds to lyophilized preparation 2-10 hour, can obtain Bolengsu lipidosome freeze-dried injection.
An object of the present invention, provide a kind of pharmaceutical composition prepare anti-liver injury, the liver protecting and ALT lowering, suppression hepatitis B replication effect medicine in purposes; Described medicine can be used for the treatment of hepatic injury, hepatitis B.
Detailed description of the invention
Following examples further illustrate of the present invention, but never limit the scope of the present invention.Elaborate the present invention further referring to embodiment, but it will be appreciated by those skilled in the art that the present invention is not limited to the preparation method of these embodiments and use.And those skilled in the art can carry out equivalent replacement, combination, improvement to the present invention according to description of the invention or modify, but these all will comprise within the scope of the invention.
Embodiment 1 tablet
(1) formula of Bolengsu tablet
1g Bolengsu, 10g PHOSPHATIDYL ETHANOLAMINE, starch 25g, 75% ethanol of carmethose 18g, 50ml.
(2) Bolengsu method for preparing tablet thereof
(1) Bolengsu of recipe quantity, PHOSPHATIDYL ETHANOLAMINE are dissolved in 75% ethanol, for subsequent use;
(2) by starch, the pulverizing such as sodium carboxymethyl cellulose, cross 80 mesh sieves, mix homogeneously, for subsequent use;
(3) (2) adjuvant is added the ethanol in (1), use fluidized bed granulation, until without residual powder, drying obtains primary granule.
(4) the primary granule tabletting will obtained in (3), obtains ripple rib disintegrating tablet
Comparative example 1 tablet
(1) formula of Bolengsu tablet
1g Bolengsu, starch 25g, 75% ethanol of sodium carboxymethyl cellulose 18g, 50ml.
(2) Bolengsu tablet producing technology
(1) Bolengsu of recipe quantity is dissolved in 75% ethanol, for subsequent use;
(2) by starch, the pulverizing such as sodium carboxymethyl cellulose, cross 80 mesh sieves, mix homogeneously, for subsequent use;
(3) (2) adjuvant is added the ethanol in (1), use fluidized bed granulation, until without residual powder, drying obtains primary granule.
(4) the primary granule tabletting will obtained in (3), obtains solid preparation
embodiment 2 injection
(1) formula of Bolengsu injection
0.08g Bolengsu, 1g PHOSPHATIDYL ETHANOLAMINE, 5ml glycerol, 2.5g glucose sugar and appropriate sodium dihydrogen phosphate
(2) Bolengsu process for preparation of injection
(1) Bolengsu, PHOSPHATIDYL ETHANOLAMINE are dissolved in glycerol, for subsequent use;
(2) solution in (1) that obtains and sodium dihydrogen phosphate are added water for injection, regulate PH to 7.0;
(3) solution obtained in (2) is added glucose, regulate osmotic pressure, sterilizing, namely obtains liquid preparation.
Comparative example 2 injection
(1) formula of Bolengsu injection
0.08g Bolengsu, 5ml glycerol, 2.5g glucose sugar and appropriate sodium dihydrogen phosphate
(2) Bolengsu process for preparation of injection
(1) Bolengsu is dissolved in glycerol, for subsequent use;
(2) solution in (1) that obtains and sodium dihydrogen phosphate are added water for injection, regulate PH to 7.0;
(3) solution obtained in (2) is added glucose, regulate osmotic pressure, sterilizing, namely obtains liquid preparation.
embodiment 3 liposome
(1) formula composition:
0.32mg Bolengsu, 10.1mg PHOSPHATIDYL ETHANOLAMINE, 2.52mg cholesterol, 10mL dichloromethane.(2) preparation technology
(1) according to the preferred prescription ratio of uniform Design, take Bolengsu, PHOSPHATIDYL ETHANOLAMINE and cholesterol, be dissolved in q. s. methylene chloride.
(2) proceeded to by the mixed solution that (1) obtains in 500mL ground round-bottomed flask, 30 DEG C of water-bath decompression removing dichloromethane, make filmogen bottom bottle, form an even lipid membrane.
(3) the even lipid membrane that (2) obtain is added appropriate span80 aqueous solution, at 40 DEG C, Rotary Evaporators rotates and washes film 30min.
(4) the lipid membrane eluting (3) obtained hydration become liposome just suspension, and water bath sonicator, crosses 0.22 μm of filter membrane, obtain Bolengsu liposome.
Comparative example 3a liposome
(1) formula composition:
0.31mg Bolengsu, 9.9mg soybean phospholipid, 2.52mg cholesterol, 10mL dichloromethane.
(2) preparation technology
(1) according to the preferred prescription ratio of uniform Design, take Bolengsu, soybean phospholipid, cholesterol, be dissolved in q. s. methylene chloride.
(2) proceeded to by the mixed solution that (1) obtains in 500mL ground round-bottomed flask, 30 DEG C of water-bath decompression removing dichloromethane, make filmogen bottom bottle, form an even lipid membrane.
(3) the even lipid membrane that (2) obtain is added appropriate span80 aqueous solution, at 40 DEG C, Rotary Evaporators rotates and washes film 30min.
(4) the lipid membrane eluting (3) obtained hydration become liposome just suspension, and water bath sonicator, crosses 0.22 μm of filter membrane, obtain Bolengsu liposome.
Comparative example 3b liposome
(1) formula composition:
0.31mg Bolengsu, 9.76mg soybean phospholipid, 2.44mg cholesterol, 10mL chloroform.
(2) preparation technology
(1) according to the preferred prescription ratio of uniform Design, take Bolengsu, soybean phospholipid and cholesterol, be dissolved in appropriate chloroform.
(2) mixed solution that (1) obtains is proceeded in 500mL ground round-bottomed flask, 30 DEG C of water-bath chloroform removed under pressure, make filmogen bottom bottle, form an even lipid membrane.
(3) the even lipid membrane that (2) obtain is added certain density F68 aqueous solution, at 50 DEG C, Rotary Evaporators rotates and washes film 30min.
(4) the lipid membrane eluting (3) obtained hydration become liposome just suspension, and water bath sonicator, crosses 0.22 μm of filter membrane, obtain Bolengsu liposome.
Embodiment 4 liposome freeze-drying powder injection
(1) formula composition:
Bolengsu liposome 125ml, sucrose 6.25g, lactose 6.25g that embodiment 3 must obtain
(2) preparation technology:
(1) the Bolengsu liposome that enforcement 3 obtains is added sucrose and the lactose of recipe quantity, stir and make it all dissolve, be dispensed in the bottle of Xining.
(2) in the refrigerator that the Xining bottle that suspension is housed (1) obtained puts into-40 DEG C freezing 5 hours, proceed to lyophilized preparation 7 hours, Bolengsu lipidosome freeze-dried injection can be obtained.
Comparative example 4a liposome freeze-drying powder injection
(1) formula composition:
Bolengsu liposome 125ml, sucrose 6.25g, lactose 6.25g that comparative example 3a obtains
(2) preparation technology:
(1) the Bolengsu liposome obtained by comparative example 3a adds sucrose and the lactose of recipe quantity, stirs and makes it all dissolve, be dispensed in the bottle of Xining.
(2) in the refrigerator that the Xining bottle that suspension is housed (1) obtained puts into-40 DEG C freezing 5 hours, proceed to lyophilized preparation 7 hours, Bolengsu lipidosome freeze-dried injection can be obtained.
Comparative example 4b liposome
(1) formula composition:
Bolengsu liposome 125ml, sucrose 6.25g, lactose 6.25g that comparative example 3b obtains
(2) preparation technology:
(1) the Bolengsu liposome obtained by comparative example 3b adds sucrose and the lactose of recipe quantity, stirs and makes it all dissolve, be dispensed in the bottle of Xining.
(2) in the refrigerator that the Xining bottle that suspension is housed (1) obtained puts into-40 DEG C freezing 5 hours, proceed to lyophilized preparation 7 hours, Bolengsu lipidosome freeze-dried injection can be obtained.
Embodiment 5 bioavailability is tested
Adopt the single centre EXPERIMENTAL DESIGN of open, random, dual crossing, two cycles, single oral dose.20 health volunteers are divided into A, B2 group at random, often organize the Bolengsu tablet that embodiment 1 is taken in subject per's test respectively, prepared by comparative example 1.Experimenter is before test after 1d dinner, and water 12h is can't help in fasting, and next day is the oral above-mentioned Bolengsu tablet of empty stomach early, with 200mL warm water delivery service, and notes down.Take medicine after 2h and carry out unified standard breakfast, can freely drink water.Duration of test is guarded by medical personnel, and tested period avoids strenuous exercise.Before experimenter takes medicine and after taking medicine 0.5,1.0,2.0,3.0,4.0,5.0,6.0,8.0,10,12,16 and 24h respectively get veins of upper extremity blood 4ml, anticoagulant heparin, get blood plasma ,-20 DEG C of preservations, thaw at RT during mensuration for centrifugal point after placing 30min.Adopt high-efficient liquid phase technique to measure the Bolengsu in blood plasma, data are as follows:
Table 1 pharmacokinetic parameters
As can be seen from the above experimental data, tablet prepared by the embodiment of the present invention 1 is compared with comparative example, and bioavailability improves greatly, has absolutely proved that the present invention is owing to adding PHOSPHATIDYL ETHANOLAMINE, improve bioavailability widely, obtain unexpected technical effect.
Embodiment 6 bioavailability is tested
Adopt the single centre EXPERIMENTAL DESIGN of open, random, dual crossing, two cycles, single oral dose.20 health volunteers are divided into A, B2 group at random, often organize the Bolengsu injection that embodiment 2 is injected in subject per's test respectively, prepared by comparative example 2.Experimenter is before test after 1d dinner, and water 12h is can't help in fasting, and next day early injects above-mentioned Bolengsu injection, and notes down.Carry out unified standard breakfast after administration 2h, can freely drink water.Duration of test is guarded by medical personnel, and tested period avoids strenuous exercise.Before experimenter takes medicine and after taking medicine 0.5,1.0,2.0,3.0,4.0,5.0,6.0,8.0,10,12,16 and 24h respectively get veins of upper extremity blood 4ml, anticoagulant heparin, get blood plasma ,-20 DEG C of preservations, thaw at RT during mensuration for centrifugal point after placing 30min.Adopt high-efficient liquid phase technique to measure the Bolengsu in blood plasma, data are as follows:
Table 2 pharmacokinetic parameters
As can be seen from the above experimental data, injection prepared by the embodiment of the present invention 2 is compared with comparative example, and bioavailability improves greatly, has absolutely proved that the present invention is owing to adding PHOSPHATIDYL ETHANOLAMINE, improve bioavailability widely, obtain unexpected technical effect.
experimental example 7the mensuration of envelop rate
The liposome prepared in embodiment 3 and comparative example 3a, 3b is got 0.5mL, is placed in Millpore super filter tube, after the centrifugal 10min of 4000rpm, collect filtrate, the free drug content in liposome solutions is designated as W
free; It is appropriate that another precision measures HPT liposome solutions, adds the ultrasonic 10min of methanol of 20 times amount, be measured in the same method HPT content, be designated as W
always, adopt Ultra Performance Liquid Chromatography according to following formulae discovery envelop rate: envelop rate (EE%)=(1-W
free/ W
always) × 100%, result is shown in following table 3.
Table 3 entrapment efficiency determination result
As shown in Table 3, the envelop rate of the Liposomal formulation of embodiment 3 preparation is significantly higher than the envelop rate of the Liposomal formulation of comparative example 3a and 3b.Illustrate when using the composition beyond the present invention's composition used, or when Ingredient Amount is when the Ingredient Amount scope that the present invention limits is outer, the liposome encapsulation of gained liposome is lower than the present invention.
Embodiment 8 bioavailability is tested
Adopt the single centre EXPERIMENTAL DESIGN of open, random, dual crossing, two cycles, single oral dose.30 health volunteers are divided into A, B, C etc. three groups at random, and often group subject per tests Bolengsu freeze-dried powder prepared by drug administration by injection embodiment 4, comparative example 4a, comparative example 4b respectively.Experimenter is before test after 1d dinner, and water 12h is can't help in fasting, and next day early injects above-mentioned Bolengsu preparation (joining distilled water) on an empty stomach, and notes down.Take medicine after 2h and carry out unified standard breakfast, can freely drink water.Duration of test is guarded by medical personnel, and tested period avoids strenuous exercise.Before experimenter takes medicine and after taking medicine 0.5,1.0,2.0,3.0,4.0,5.0,6.0,8.0,10,12,16 and 24h respectively get veins of upper extremity blood 4ml, anticoagulant heparin, get blood plasma ,-20 DEG C of preservations, thaw at RT during mensuration for centrifugal point after placing 30min.Adopt high-efficient liquid phase technique to measure the Bolengsu in blood plasma, data are as follows:
Table 4 pharmacokinetic parameters
As can be seen from the above experimental data, liposome prepared by the embodiment of the present invention 4 is compared with comparative example, and bioavailability improves greatly, has absolutely proved that the present invention is owing to adding PHOSPHATIDYL ETHANOLAMINE, improve bioavailability widely, obtain unexpected technical effect.
Claims (8)
1. improve the bioavailability of Bolengsu and a pharmaceutical composition for curative effect, it is characterized in that described compositions comprises Bolengsu and PHOSPHATIDYL ETHANOLAMINE.
2. pharmaceutical composition according to claim 1, is characterized in that, based on parts by weight, and Bolengsu 1-10 part and acyl ethanolamine 10-100 part.
3. pharmaceutical composition according to claim 2, is characterized in that described pharmaceutical composition is selected from pharmaceutically acceptable pharmaceutical formulations, based on parts by weight, comprises Bolengsu 1-10 part and acyl ethanolamine 10-100 part and pharmaceutically acceptable excipient.
4., containing a solid preparation for Bolengsu and PHOSPHATIDYL ETHANOLAMINE, it is characterized in that comprising based on 1-5 part Bolengsu of parts by weight, 10-50 part PHOSPHATIDYL ETHANOLAMINE, filler 10-100 part, disintegrating agent 10-100 part.
5., containing a liquid preparation for Bolengsu and PHOSPHATIDYL ETHANOLAMINE, it is characterized in that comprising based on 0.05-0.5 part Bolengsu of parts by weight, 0.5-2 part PHOSPHATIDYL ETHANOLAMINE, 1-10 part glycerol, 1-5 part glucose sugar and appropriate sodium dihydrogen phosphate; Preferably comprise based on 0.08 part of Bolengsu of parts by weight, 1 part of PHOSPHATIDYL ETHANOLAMINE, 5 parts of glycerol, 2.5 portions of glucose sugar and appropriate sodium dihydrogen phosphate.
6., containing a Liposomal formulation for Bolengsu and PHOSPHATIDYL ETHANOLAMINE, it is characterized in that comprising based on parts by weight, 0.1-1 part Bolengsu, 5-15 part PHOSPHATIDYL ETHANOLAMINE, 1-5 part cholesterol; Preferably comprise based on 0.32 part of Bolengsu of parts by weight, 10.1 parts of PHOSPHATIDYL ETHANOLAMINE, 2.52 parts of cholesterol.
7. contain a freeze-dried powder for the Liposomal formulation of Bolengsu and PHOSPHATIDYL ETHANOLAMINE, it is characterized in that comprising 50-200 part Bolengsu liposome, 5-25 part sucrose, the 5-25 part lactose based on parts by weight; Preferably comprise based on 125 parts of Bolengsu liposomees of parts by weight, 6.25 parts of sucrose, 6.25 parts of lactose.
8. claim 1 pharmaceutical composition prepare anti-liver injury, the liver protecting and ALT lowering, suppression hepatitis B replication effect medicine in purposes; Described medicine can be used for the treatment of hepatic injury, hepatitis B.
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| CN201410378372.8A CN105311637B (en) | 2014-08-04 | 2014-08-04 | A kind of pharmaceutical composition containing Bolengsu |
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| CN201410378372.8A CN105311637B (en) | 2014-08-04 | 2014-08-04 | A kind of pharmaceutical composition containing Bolengsu |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1486691A (en) * | 2003-05-29 | 2004-04-07 | 中国人民解放军第三○二医院 | Bolengsu compound and its prepn, medicine composition and use |
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2014
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1486691A (en) * | 2003-05-29 | 2004-04-07 | 中国人民解放军第三○二医院 | Bolengsu compound and its prepn, medicine composition and use |
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