CN103623345A - Preparation method of antivirus oral liquid - Google Patents

Preparation method of antivirus oral liquid Download PDF

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Publication number
CN103623345A
CN103623345A CN201310609317.0A CN201310609317A CN103623345A CN 103623345 A CN103623345 A CN 103623345A CN 201310609317 A CN201310609317 A CN 201310609317A CN 103623345 A CN103623345 A CN 103623345A
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volatile oil
preparation
oral liquid
solution
antivirus oral
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CN103623345B (en
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刘志庆
王翠霞
贾晓璐
苗海敏
王娜
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ZHENGZHOU DAMING PHARMACEUTICAL TECHNOLOGY Co Ltd
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ZHENGZHOU DAMING PHARMACEUTICAL TECHNOLOGY Co Ltd
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Abstract

The invention discloses a preparation method of antivirus oral liquid. The preparation method comprises the following steps: firstly crushing reed rhizome, radix rehmanniae, radix curcumae, rhizoma acori graminei, radix isatidis, pogostemon cablin, rhizoma anemarrhenae, forsythia and gypsum, uniformly mixing, extracting by using a water vapor distillation method, separating so as to obtain volatile oil and an extracting solution; concentrating the extracting solution, dehydrating the volatile oil, dissolving and treating the dehydrated volatile oil, phospholipid and cholesterol in a solvent so as to obtain a volatile oil liposome solution; adding auxiliary materials to the concentrated solution, adjusting the pH value, then adding the volatile oil liposome solution to the concentrated solution for fixing the volume, filtering so as to obtain the antivirus oral liquid, finally filling and sterilizing. According to the preparation method, liposome is used for encapsulating the volatile oil, so that the encapsulation efficiency is relatively high, and the encapsulation rate can reach about 95%. The preparation method is used for preparing the antivirus oral liquid and can be used for obviously improving the stability of the volatile oil and ensuring the curative effect of a product.

Description

The preparation method of antivirus oral liquid
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of preparation method of antivirus oral liquid.
Background technology
Antivirus oral liquid is market application Chinese medicine preparation very widely, the clinical treatment that is mainly used in anemopyretic cold and influenza.In pharmacopeia, the formulation and technology of antivirus oral liquid is as follows:
The formula of existing antivirus oral liquid is Radix Isatidis 129g, Gypsum Fibrosum 57g, Rhizoma Phragmitis 61g, Radix Rehmanniae 32g, Radix Curcumae 25g, Rhizoma Anemarrhenae 25g, Rhizoma Acori Graminei 25g, Herba Pogostemonis 29g and Fructus Forsythiae 46g.Its existing preparation method is:
Above nine taste medicines are decocted with water to twice, 3 hours for the first time, collect volatile oil, use HYDROXYPROPYL BETA-CYCLODEXTRIN enclose, or 1.5 hours for the first time (collecting volatile oil and volatile oil emulsion) simultaneously; 1 hour 20 minutes for the second time, filter, filtrate merges, be concentrated into appropriate, adding more than 85% ethanol, to make containing alcohol amount be 70%, standing, filtration, gained filtrate recycling ethanol is also concentrated into appropriate, adds volatile oil clathrate compound and proper honey, sucrose, flavoring orange essence, sodium cyclamate or adds volatile oil, volatile oil emulsion and proper honey, sucrose; Add water to 1000mL, mix, filtration, embedding, sterilization, obtain.And in the working standard of pharmacopeia, the pH value of regulation antivirus oral liquid should remain between 4.0~6.0.
Owing to containing volatile oil in the medical materials such as Fructus Forsythiae, Herba Pogostemonis, Rhizoma Acori Graminei, Radix Curcumae in the existing formula of antivirus oral liquid, according to existing bibliographical information, in pharmacodynamic experiment proof antivirus oral liquid patchouli alcohol have good bring down a fever, antibacterial action, but current extraction process adopts water extract-alcohol precipitation, the volatile ingredient extracting directly joins in oral liquid, because volatile oil water solublity is less and volatile.So, when being added to, volatile oil joins in filtrate, and in embedding and sterilization process, volatile oil can lose, and along with the prolongation of standing time, in finished product, volatile ingredient also can lose totally gradually.By study on the stability, finished product was placed after 1 year, and its volatile oil (take patchouli alcohol as investigating index) content significantly declines.Therefore, finished product stability is poor, may affect the former effective in cure of product; And because volatile oil has strong zest taste, affecting mouthfeel, child is difficult to accept.Be necessary to improve the existing method of preparing antivirus oral liquid for this reason, guarantee the volatile oil effective ingredient in product.
At present, also relevant for the Patents bibliographical information of antivirus oral liquid.For example: 1, application number is 02136474.5, name is called the application for a patent for invention of " antivirus oral liquid ".2, application number is 200610048411.3, name is called the application for a patent for invention of " preparation method of concentrated anti-virus oral administration liquid ".3, application number is 201210536048.5, name is called the application for a patent for invention of " a kind of antivirus oral liquid preparation method and products thereof ".4, application number is 200610122442.9, name is called the application for a patent for invention of " new technology of preparing antivirus oral liquid ".
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of preparation method of antivirus oral liquid.The antivirus oral liquid of preparing by technical solution of the present invention can effectively improve the active constituent content in product and improve the stability of product.
In order to address the above problem, the technical scheme that the present invention takes is:
The invention provides a kind of preparation method of antivirus oral liquid, comprise that pretreatment with Chinese medicine, extraction, preparation, dosing and fill concentrated, stearopten plastid sterilize, wherein:
A, pretreatment: according to the raw material of Rhizoma Phragmitis 400g, Radix Rehmanniae 200g, Radix Curcumae 175g, Rhizoma Acori Graminei 175g, Radix Isatidis 900g, Herba Pogostemonis 225g, Rhizoma Anemarrhenae 175g, Fructus Forsythiae 350g and Gypsum Fibrosum 400g, form, take various raw materials, the various raw materials that take are pulverized respectively, cross 5~10 mesh sieves, medicated powder mix homogeneously by after sieving, obtains mixed powder;
B, the mixed powder that step a is obtained adopt steam distillation to extract, and after extraction, by oil water separator, make volatile oil and extracting solution; The medicinal residues water obtaining after extraction extracts again, filters and makes extracting solution, and twice gained extracting solution merged;
C, the extracting solution obtaining after step b is merged add dehydrated alcohol, filter after standing, and gained filtrate, by decompression recycling ethanol, concentrates extracting solution, are concentrated in right amount, obtain concentrated solution;
The preparation of d, stearopten plastid: the volatile oil that step b is made dewaters, then adopt injection method, volatile oil 20~30mL after 35~50g phospholipid, 15~25g cholesterol and dehydration is dissolved in 100~200mL organic solvent, after dissolving, gained solution is slowly expelled in 500mL, the water of 30~50 ℃ by syringe under stirring condition, inject rear continuation and stirred 1~3h, then remove organic solvent, remaining liq is down to room temperature, obtains volatile oil liposome solutions;
E, dosing: the concentrated solution that step c is made adds other adjuvants, adjust pH to 5.0~6.0 with the sodium hydroxide solution of mass percentage concentration 10%, and the volatile oil liposome solutions that then adds steps d to obtain, uses purified water standardize solution, filters, and obtains antivirus oral liquid; Finally carry out fill, sterilizing.
According to the preparation method of above-mentioned antivirus oral liquid, described in step c, be concentrated in right amount, the extracting solution obtaining after concentrating accounts for 10~15% of former extracting solution weight.
According to the preparation method of above-mentioned antivirus oral liquid, phospholipid described in steps d is at least one in lecithin, hydrolecithin and soybean phospholipid.
According to the preparation method of above-mentioned antivirus oral liquid, after dissolving described in steps d, gained solution is slowly expelled in 500mL, the water of 30~50 ℃ by syringe under stirring condition, its mixing speed is 50~500r/min.
According to the preparation method of above-mentioned antivirus oral liquid, organic solvent described in steps d is ether or ethanol.
According to the preparation method of above-mentioned antivirus oral liquid, other adjuvants described in step e are Mel 800g, acesulfame potassium 700g and flavoring orange essence 10mL.
In preparation method of the present invention, stearopten plastid solution manufacturing method, except adopting injection method, can also adopt the reverse way of distillation, film dispersion method, ultrasound wave dispersion method, freeze-drying etc.Product prepared by the present invention is oral liquid, and clarity be there are certain requirements, and liposome particle diameter is required to be controlled at 1~10 μ m, and envelop rate requires to reach more than 90% simultaneously.Therefore, the present invention is through testing the definite preparation method of injection method as liposome solutions of usining.
positive beneficial effect of the present invention:
1, technical solution of the present invention is passed through the pretreatment to medical material, thereby improves the extraction efficiency of effective ingredient, increases the content of effective ingredient in product, thereby improves the curative effect of product.
2, technical solution of the present invention adopts liposome to seal volatile oil, adopt the technology of cyclodextrin inclusion compound to compare with prior art, its efficiency is higher, and (prior art adopts cyclodextrin inclusion compound, its inclusion rate is 40~85%, and the present invention adopts liposome to seal volatile oil, its envelop rate can reach 95% left and right), refer to the measurement result of table 1 liposome encapsulation of the present invention.In addition, adopt technical solution of the present invention to prepare antivirus oral liquid, can obviously improve the stability of volatile oil, guarantee the curative effect of product, refer to table 2 product stability result of the test of the present invention.
the specific embodiment:
Below in conjunction with embodiment, further set forth the present invention, but do not limit content of the present invention.All and technical scheme equivalence of the present invention all belongs to protection scope of the present invention.
Embodiment 1:
The preparation method of antivirus oral liquid of the present invention, its detailed step is as follows:
A, pretreatment: according to the raw material of Rhizoma Phragmitis 400g, Radix Rehmanniae 200g, Radix Curcumae 175g, Rhizoma Acori Graminei 175g, Radix Isatidis 900g, Herba Pogostemonis 225g, Rhizoma Anemarrhenae 175g, Fructus Forsythiae 350g and Gypsum Fibrosum 400g, form, take various raw materials, various raw materials are pulverized respectively, after pulverizing, cross 5~10 mesh sieves, medicated powder mix homogeneously by after sieving, obtains mixed powder;
B, extraction: to the water that adds 8 times of weight of mixed powder in the good mixed powder of step a pretreatment, be heated to boiling, vapor distillation extracts 3h, then by oil water separator, makes volatile oil 23.7mL and extracting solution 1943mL; Gained medicinal residues add the water of 5 times of weight of mixed powder again, decoct 2h, filter and make extracting solution, merge the extracting solution of twice gained;
C, concentrated: add dehydrated alcohol in the extracting solution after merging, make concentration of alcohol reach 70%, standing 24h filters, and filtrate, by decompression recycling ethanol, is concentrated in right amount extracting solution, obtains 1950mL concentrated solution;
The preparation of d, stearopten plastid: the volatile oil anhydrous sodium sulfate dehydration that step b is made, the anhydrous volatile oil of 20mL, 45g hydrolecithin, 24g cholesterol are dissolved in 100mL ether jointly, stirring lower solution is slowly expelled in 500mL, 50 ℃ of water by syringe, mixing speed is 350r/min, continues to stir 2h and make ether volatilization complete after injection; After being cooled to room temperature, obtain volatile oil liposome solutions, envelop rate is 94.8%;
E, dosing: after the 1950mL concentrated solution that step c is made filters, add Mel 800g, acesulfame potassium 700g and Fructus Citri tangerinae essence 10mL, sodium hydroxide solution adjust pH to 5.20 by mass percentage concentration 10%, the volatile oil liposome solutions that adds steps d to obtain, water is settled to 7000mL, filter, obtain antivirus oral liquid;
F, finally carry out fill, sterilizing: the fill of standardize solution liquid becomes 10mL/ to prop up; 121 ℃ of autoclaving 15min, gas chromatography detects, and contains patchouli alcohol 43 μ g in every 10mL antivirus oral liquid.
Embodiment 2:
The preparation method of antivirus oral liquid of the present invention, its detailed step is as follows:
A, pretreatment: according to the raw material of Rhizoma Phragmitis 400g, Radix Rehmanniae 200g, Radix Curcumae 175g, Rhizoma Acori Graminei 175g, Radix Isatidis 900g, Herba Pogostemonis 225g, Rhizoma Anemarrhenae 175g, Fructus Forsythiae 350g and Gypsum Fibrosum 400g, form, take various raw materials, various raw materials are pulverized respectively, after pulverizing, cross 5~10 mesh sieves, medicated powder mix homogeneously by after sieving, obtains mixed powder;
B, extraction: to the water that adds 8 times of weight of mixed powder in the good mixed powder of step a pretreatment, be heated to boiling, vapor distillation extracts 3h, then by oil water separator, makes volatile oil 23.7mL and extracting solution 1943mL; Gained medicinal residues add the water of 5 times of weight of mixed powder again, decoct 2h, filter and make extracting solution, merge the extracting solution of twice gained;
C, concentrated: add dehydrated alcohol in the extracting solution after merging, make concentration of alcohol reach 70%, standing 24h filters, and filtrate, by decompression recycling ethanol, is concentrated in right amount extracting solution, obtains 1950mL concentrated solution;
The preparation of d, stearopten plastid: the volatile oil anhydrous sodium sulfate dehydration that step b is made, the anhydrous volatile oil of 20mL, 45g hydrolecithin, 24g cholesterol are dissolved in 100mL ether jointly, stirring lower solution is slowly expelled in 500mL, 50 ℃ of water by syringe, mixing speed is 350r/min, continues to stir 2h and make ether volatilization complete after injection; After being cooled to room temperature, obtain volatile oil liposome solutions, envelop rate is 95.3%;
E, dosing: after the 1950mL concentrated solution that step c is made filters, add Mel 800g, acesulfame potassium 700g and Fructus Citri tangerinae essence 10mL, sodium hydroxide solution adjust pH to 5.20 by mass percentage concentration 10%, the volatile oil liposome solutions that adds steps d to obtain, water is settled to 7000mL, filter, obtain antivirus oral liquid;
F, finally carry out fill, sterilizing: the fill of standardize solution liquid becomes 10mL/ to prop up; 121 ℃ of autoclaving 15min, gas chromatography detects, and contains patchouli alcohol 44 μ g in every 10mL antivirus oral liquid.
Embodiment 3: substantially the same manner as Example 1, difference is:
In steps d: the anhydrous volatile oil of 25mL, 40g lecithin, 20g cholesterol are dissolved in 120mL ethanol jointly, stirring lower solution is slowly expelled in 500mL, 50 ℃ of water by syringe, mixing speed is 260r/min, continues to stir 2h and make ethanol volatilization complete after injection; After being cooled to room temperature, obtain volatile oil liposome solutions, envelop rate is 96.1%;
In step e: with the sodium hydroxide solution adjust pH to 5.0 of mass percentage concentration 10%;
In step f: gas chromatography detects, in every 10mL antivirus oral liquid, contain patchouli alcohol 43.5 μ g.
Embodiment 4: substantially the same manner as Example 1, difference is:
In steps d: the anhydrous volatile oil of 30mL, 35g soybean phospholipid, 15g cholesterol are dissolved in 150mL ethanol jointly, stirring lower solution is slowly expelled in 500mL, 50 ℃ of water by syringe, mixing speed is 400r/min, continues to stir 2h and make ethanol volatilization complete after injection; After being cooled to room temperature, obtain volatile oil liposome solutions, envelop rate is 95.1%;
In step e: with the sodium hydroxide solution adjust pH to 6.0 of mass percentage concentration 10%;
In step f: gas chromatography detects, in every 10mL antivirus oral liquid, contain patchouli alcohol 45 μ g.
Embodiment 5: the mensuration of liposome encapsulation
Get the volatile oil liposome turbid liquor having mixed, through 0.22 μ m filtering with microporous membrane, filtrate is used 100mL chloroform extraction, gets organic facies, after organic facies evaporate to dryness, add 0.5mL normal hexane to produce and process 5min, be transferred to 1mL volumetric flask, add inner mark solution, with normal hexane, be settled to 1mL, as test sample, carry out gas chromatographic analysis, by calculating, obtain patchouli alcohol content in 1mL sample, result is denoted as C 1.
Get the volatile oil liposome turbid liquor having mixed, add methanol breakdown of emulsion, use 100mL chloroform extraction, get organic facies, after organic facies evaporate to dryness, add 0.5mL normal hexane to produce and process 5min, be transferred to 1mL volumetric flask, add inner mark solution, with normal hexane, be settled to 1mL, as test sample, carry out gas chromatographic analysis, by calculating, obtain patchouli alcohol content in 1mL sample, result is denoted as C 2.
The formula of computational envelope rate is: envelop rate=(C 2-C 1)/C 2* 100%.
Measurement result is in Table 1.
Figure DEST_PATH_IMAGE001
From the measurement result of table 1, adopt technical solution of the present invention to seal its volatile oil, its envelop rate is up to 95% left and right, and compared with prior art envelop rate has had raising largely.
Embodiment 6: stability test
Get the antivirus oral liquid sample of preparing by embodiment 1 method, lot number is 20130301,20130302,20130303, the control sample 1 lot number 20130402(Guangzhou Xiang Xue Pharmacy stock Co., Ltd of purchase).
Stability test investigation method: three batch samples and reference substance are put into climatic chamber, control 40 ± 2 ℃ of temperature, humidity 75 ± 5%, respectively at the content detection of carrying out patchouli alcohol for 0,1,2,3,6 month, content detection result is as shown in table 2 below.
Figure 756436DEST_PATH_IMAGE002
From the experimental result of table 2, can find out, Chinese crude drug extracts after pulverizing again, and can improve the content of the volatile oil in product; Volatile oil after liposomal encapsulated is retained in more than 70% at content after 6 months accelerated tests, and existing product volatile oil content after 6 months accelerated tests only retains 50% effect.Prove that thus technical solution of the present invention can obviously improve the stability of volatile oil, the quality of product is more stable compared with commercially available prod.Illustrate that production method of the present invention has higher first carrying out and practicality.

Claims (6)

1. a preparation method for antivirus oral liquid, comprises preparation, dosing and the fill sterilization of pretreatment with Chinese medicine, extraction, concentrated, stearopten plastid, it is characterized in that:
A, pretreatment: according to the raw material of Rhizoma Phragmitis 400g, Radix Rehmanniae 200g, Radix Curcumae 175g, Rhizoma Acori Graminei 175g, Radix Isatidis 900g, Herba Pogostemonis 225g, Rhizoma Anemarrhenae 175g, Fructus Forsythiae 350g and Gypsum Fibrosum 400g, form, take various raw materials, the various raw materials that take are pulverized respectively, cross 5~10 mesh sieves, medicated powder mix homogeneously by after sieving, obtains mixed powder;
B, the mixed powder that step a is obtained adopt steam distillation to extract, and after extraction, by oil water separator, make volatile oil and extracting solution; The medicinal residues water obtaining after extraction extracts again, filters and makes extracting solution, and twice gained extracting solution merged;
C, the extracting solution obtaining after step b is merged add dehydrated alcohol, filter after standing, and gained filtrate, by decompression recycling ethanol, concentrates extracting solution, are concentrated in right amount, obtain concentrated solution;
The preparation of d, stearopten plastid: the volatile oil that step b is made dewaters, then adopt injection method, volatile oil 20~30mL after 35~50g phospholipid, 15~25g cholesterol and dehydration is dissolved in 100~200mL organic solvent, after dissolving, gained solution is slowly expelled in 500mL, the water of 30~50 ℃ by syringe under stirring condition, inject rear continuation and stirred 1~3h, then remove organic solvent, remaining liq is down to room temperature, obtains volatile oil liposome solutions;
E, dosing: the concentrated solution that step c is made adds other adjuvants, adjust pH to 5.0~6.0 with the sodium hydroxide solution of mass percentage concentration 10%, and the volatile oil liposome solutions that then adds steps d to obtain, uses purified water standardize solution, filters, and obtains antivirus oral liquid; Finally carry out fill, sterilizing.
2. the preparation method of antivirus oral liquid according to claim 1, is characterized in that: described in step c, be concentrated in right amount, the extracting solution obtaining after concentrating accounts for 10~15% of former extracting solution weight.
3. the preparation method of antivirus oral liquid according to claim 1, is characterized in that: phospholipid described in steps d is at least one in lecithin, hydrolecithin and soybean phospholipid.
4. the preparation method of antivirus oral liquid according to claim 1, it is characterized in that: after dissolving described in steps d, gained solution is slowly expelled in 500mL, the water of 30~50 ℃ by syringe under stirring condition, its mixing speed is 50~500r/min.
5. the preparation method of antivirus oral liquid according to claim 1, is characterized in that: organic solvent described in steps d is ether or ethanol.
6. the preparation method of antivirus oral liquid according to claim 1, is characterized in that: other adjuvants described in step e are Mel 800g, acesulfame potassium 700g and flavoring orange essence 10mL.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103961575A (en) * 2014-05-08 2014-08-06 肖勇 Chinese patent medicine for treating cold and preparation method thereof
CN109224072A (en) * 2018-11-20 2019-01-18 安徽东盛友邦制药有限公司 A kind of antiviral oral liquor of strengthen immunity and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1939525A (en) * 2006-09-27 2007-04-04 广州市香雪制药股份有限公司 Production of antiviral oral liquid
CN101002812A (en) * 2006-01-20 2007-07-25 江苏正大天晴药业股份有限公司 Medical use of volatile oil of traditional Chinese medicine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101002812A (en) * 2006-01-20 2007-07-25 江苏正大天晴药业股份有限公司 Medical use of volatile oil of traditional Chinese medicine
CN1939525A (en) * 2006-09-27 2007-04-04 广州市香雪制药股份有限公司 Production of antiviral oral liquid

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103961575A (en) * 2014-05-08 2014-08-06 肖勇 Chinese patent medicine for treating cold and preparation method thereof
CN109224072A (en) * 2018-11-20 2019-01-18 安徽东盛友邦制药有限公司 A kind of antiviral oral liquor of strengthen immunity and preparation method thereof
CN109224072B (en) * 2018-11-20 2022-05-03 安徽东盛友邦制药有限公司 Antiviral oral liquid for enhancing immunity and preparation method thereof

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