CN105663520B - Five brave oral solutions and preparation method thereof - Google Patents
Five brave oral solutions and preparation method thereof Download PDFInfo
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- CN105663520B CN105663520B CN201610113641.7A CN201610113641A CN105663520B CN 105663520 B CN105663520 B CN 105663520B CN 201610113641 A CN201610113641 A CN 201610113641A CN 105663520 B CN105663520 B CN 105663520B
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/238—Saposhnikovia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/286—Carthamus (distaff thistle)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
- A61K36/8884—Arisaema, e.g. Jack in the pulpit
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
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- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Abstract
The present invention relates to brave oral solutions of one kind five and preparation method thereof, raw material contains the component of following parts by weight: 100-150 parts of Radix Angelicae Sinensis, 100-150 parts of safflower, 100-150 parts of Rhizoma Arisaematis (processed), 100-150 parts of radix saposhnikoviae, 68-104 parts of the root of Dahurain angelica, 1-5 parts of Tween-80,0.5-3 parts of steviol glycoside, 0.3-2 parts of sodium pyrosulfite, 1-6 parts of mosatil.The brave oral solution of the present invention five improves the utilization rate of pharmaceutical raw material, make product analgesic, it is anti-inflammatory and in terms of drug effect enhanced, and improve product stability.
Description
Technical field
The invention belongs to technical field of traditional Chinese medicines, it is related to Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed), root of Dahurain angelica five kinds of Chinese medicine being effective
Brave oral solution of the oral liquid of ingredient, especially one kind five and preparation method thereof.
Background technique
The scattered original side of five tigers comes from the Qing Dynasty " raising the side He Tingji ", is the good medicine for treating traumatic injury, blood stasis and swelling pain, to go through
Version " Chinese Pharmacopoeia " is recorded.Since the scattered original side of five tigers is powder.Powder works very fast but relatively modern quick-acting relative to pill
Etc. it is then relatively slow for dosage forms, there are inconvenient to use, poor bioavailability, the deficiencies of quality of the pharmaceutical preparations is difficult to control place.It is oral
Liquor ratio pill and powder absorb it is fast, it is in good taste compared with tincture, irritation is small.
Five brave oral solutions are the new drugs that form improvement development is carried out according to the scattered prescription of five tigers in " Chinese Pharmacopoeia ".Deng Hongzhu etc.
(drug efficacy study of five brave oral solutions, No.1 Military Medical Univ.'s journal, the publication date: 2000, issue: the 3rd phase, call background document in the following text
1) the pain stop and anti-inflammation effect and the influence to animal model with blood stasis hemorheology for disclosing five brave oral solutions.The result shows that nothing
There are apparent analgesic, anti-inflammatory effect by oral solution or powder, and the whole blood viscosity and HCT of rat's blood stasis model can be reduced, but mouth
It is rapid-action in terms of pain stop and anti-inflammation compared with powder to take liquid, other than curative effect is improved compared with powder, oral solution also overcomes powder presence
Take it is inconvenient, absorb it is poor, the deficiencies of Hygienic Index is difficult to reach requirement, quality is difficult to control place.Tan Xiaomei etc. (five
The research of ferulaic acid content measuring method in brave oral solution, Chinese medicine, 2003, (the 6th phase), call background document 2 in the following text) disclose five
The content assaying method of the effective component ferulic acid of monarch drug in a prescription Radix Angelicae Sinensis in brave oral solution.Method: high performance liquid chromatography, chromatography are used
Column: C18 column (125 × 4mm, 5 μm)；Mobile phase: -1% acetic acid of methanol (24: 76)；Theoretical cam curve is not less than in terms of ferulic acid
1500；Detection wavelength: 313nm. result: the range of linearity of ferulaic acid content is 0.11~0.385 μ g, r=0.9999, average to add
The sample rate of recovery is 100.79%, RSD=1.87%.This method is simple and reliable, easily operated, and sensitive, accurate, specificity is strong, weight
Existing property is good, can be used for the measurement and quality control of ferulaic acid content in five brave oral solutions.
But the dosage and preparation process of each medicinal material of the undisclosed five brave oral solution of background document 1, it is also not publicly auxiliary used in it
Material.The study found that five brave oral solutions of conventional method preparation are there are the weakness that effective component in pharmacy procedure is lost, drug effect is not
Good, especially active constituent asafoetide absolute acid stability is poor, content decline easily occurs, limits the popularization and application of five brave oral solutions.
Summary of the invention
The purpose of the present invention is intended to that existing five tiger is overcome to dissipate existing drawbacks described above, provides the brave oral solution of one kind five and its system
Preparation Method, the five brave oral solution are a kind of oral liquids of pure Chinese medicine pharmaceutical composition, and this product has activating microcirculation and removing stasis medicinal, and detumescence stops
The effects of pain.For treating the illnesss such as traumatic injury, blood stasis and swelling pain, strain.This product is small, in good taste with taking dose, takes
Conveniently, absorption is very fast, work rapid, bioavilability height, effective component ferulic acid quality stabilization, simple production process etc. are excellent
Point.
Realize that the object of the invention technical solution is as follows:
The brave oral solution of one kind five, raw material contain the component of following parts by weight: 100-150 parts of Radix Angelicae Sinensis, 100-150 parts
Safflower, 100-150 parts of radix saposhnikoviae, 100-150 parts of Rhizoma Arisaematis (processed), 68-104 parts of the root of Dahurain angelica, 1-5 parts of Tween-80,0.5-3
Steviol glycoside, 0.3-2 parts of the sodium pyrosulfite, 1-6 parts of mosatil of part.
Preferably, described five brave oral solution, raw material contain the component of following parts by weight: 128 parts of Radix Angelicae Sinensis, 128 parts
Safflower, 128 parts of radix saposhnikoviae, 128 parts of Rhizoma Arisaematis (processed), 88 parts of the root of Dahurain angelica, 3 parts of Tween-80,1 part of steviol glycoside, 1 part
Sodium pyrosulfite, 2 parts of mosatil.
It is further preferred that of the present invention five brave oral solutions, include following so that its raw material in terms of 1000mL oral solution is made
Component: 100-150g Radix Angelicae Sinensis, 100-150g safflower, 100-150g radix saposhnikoviae, 100-150g Rhizoma Arisaematis (processed), the 68-104g root of Dahurain angelica, 1-5g
Tween-80,0.5-3g steviol glycoside, the sodium pyrosulfite of 0.3-2g, 1-6g mosatil.
Preferably, described five brave oral solutions, include following components so that oral solution in terms of 1000mL is made to count its raw material: 128g works as
Return, 128g safflower, 128g radix saposhnikoviae, 128g Rhizoma Arisaematis (processed), the 88g root of Dahurain angelica, the Tween-80 of 3g, the steviol glycoside of 1g, 1g burnt sulfurous
The mosatil of sour sodium, 2g.
Preferably, the five tiger oral solution pH is 4.0-6.0；Further preferred pH is 5.0.
Parts by weight of the present invention can be the unit of weight well known in the art such as μ g, mg, g, kg, be also possible to it again
Number, such as 1/10,1/100,10 times, 100 times.
On the basis of not influencing drug effect and stability, its raw material of five tiger oral solution of the present invention may also include pharmaceutically
Available additive on available auxiliary material and/or food.
The present invention also provides the preparation methods of above-mentioned five brave oral solutions, comprising the following steps:
1) by formula weigh required raw material (i.e. Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed), the root of Dahurain angelica, Tween-80, steviol glycoside,
Sodium pyrosulfite, mosatil etc.)；
2) after mixing Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica, adding the concentration of 5-10 times of weight is 60%-70%
Ethyl alcohol, refluxing extraction 1-3 times is 1-2 hours each, filters by several times, merging filtrate, recycles ethyl alcohol；It is concentrated under reduced pressure into relative density
1.02-1.08 (50-70 DEG C), obtains concentrate；
3) concentrate obtained by step 2) is clarified using chitosan or " ZTC1+1 " clarifying agent, filters to obtain clarified solution；
4) edible alcohol is added into clarified solution obtained by step 3), makes alcoholic strength to 7%-12% (referring to volumetric concentration), stirs
It mixes uniformly；Filtrate is collected in filtering；
5) Tween-80, steviol glycoside, sodium pyrosulfite, mosatil is added by formula into filtrate obtained by step 4),
It stirs evenly；Purified water constant volume is added, adjusts pH value, stirs evenly, filters；
6) filling, sterilizing to get.
The preparation method of above-mentioned five brave oral solutions, in which:
Preferably, step 2) will add the concentration of 8 times of weight to be after Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica mix
70% ethyl alcohol refluxing extraction 3 times, 2 hours every time, filters, merging filtrate by several times, recycles ethyl alcohol；It is concentrated under reduced pressure into relative density
1.07 (50 DEG C), obtain concentrate, put to room temperature.
Preferably, described concentrate obtained by step 2) is carried out clear method using chitosan includes: to make to step 3)
At 1000mL oral solution meter, it is that (i.e. solvent is body to -1% acetum of 2% chitosan that mass concentration, which is added, into gained concentrate
The acetum of product concentration 1%) 50~100mL, it is sufficiently stirred, is heated to 60-70 DEG C of heat preservation 10-30min, puts to room temperature, mistake
Filter, takes supernatant；Or
Preferably, step 3) is described carries out clear method packet using " ZTC1+1 " clarifying agent for concentrate obtained by step 2)
Include: to be made in terms of 1000mL oral solution, be added into gained concentrate 1% acetum 30 of 2% " ZTC1+1 " B component~
100mL is sufficiently stirred, and is heated to 60 DEG C of heat preservation 10-20min, adds the aqueous solution 15-60mL of 2% " ZTC1+1 " component A,
60 DEG C of heat preservation 10-20min are put to room temperature, and filtering takes supernatant.
Commercial goods can be used in chitosan clarifier of the present invention；" ZTC1+1 " clarifying agent is the positive day Cheng Cheng in Beijing
Clear Technology Co., Ltd. commercial goods product.
Preferably, it is filtered into described in step 4) after diatomite is added and is filtered using plate filter；It is further preferred that silicon
The dosage of diatomaceous earth is the 1%-3% of medical fluid weight.
Preferably, available additive on pharmaceutically available auxiliary material and/or food can also be added in step 5)；To increase
The stability of the strong oral solution adjusts mouthfeel；But on the basis of not influencing drug effect and stability.
Preferably, step 6) sterilizing methods are 121 DEG C of sterilizing about 8-15min；Or 100 DEG C sterilize 30 minutes.
The present invention can be used this field routine pH adjusting agent and adjust pH value, such as sodium hydroxide, hydrochloric acid etc..
The brave oral solution of the present invention five recommends dose are as follows: each 5-20mL, 2 times a day；It is preferred that each 10mL, 2 times a day.
The brave oral solution of the present invention five is the new drug that form improvement development is carried out according to the scattered prescription of five tigers in " Chinese Pharmacopoeia ".Change
Reach after Cheng Wuhu oral solution taking dose it is small, it is in good taste, convenient to take, absorb it is very fast, work rapidly, bioavilability it is high,
The purpose of effective component ferulic acid quality stabilization, simple production process, easily controllable product quality.
The invention has the benefit that
The brave oral solution of the present invention five improves the utilization rate of pharmaceutical raw material, makes product in analgesic, anti-inflammatory and promoting blood circulation to remove blood stasis etc.
The drug effect of aspect is enhanced, and improves product stability.
Specific embodiment
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..It is not specified in embodiment specific
Technology or conditions person, described technology or conditions according to the literature in the art, or carried out according to product description.It is used
Production firm person is not specified in reagent or instrument, is the conventional products that can be commercially available by regular distributor.Wherein, chitosan
Clarifying agent is provided by Zhejiang golden shell pharmaceutcal corporation, Ltd；" ZTC1+1 " clarifying agent is mentioned by the positive day in Beijing at clarification technique Co., Ltd
For；Ovalbumin clarifying agent is provided by Sinopharm Chemical Reagent Co., Ltd..
Embodiment 1
The brave oral solution of one kind five, raw material contain the component of following parts by weight: 100 parts of Radix Angelicae Sinensis, 100 parts of safflower, 100
The Rhizoma Arisaematis (processed), 100 parts of radix saposhnikoviae, 68 parts of the root of Dahurain angelica, 1 part of Tween-80,0.5 part of steviol glycoside, 0.3 part of coke of part are sub-
Sodium sulphate, 1 part of mosatil.The pH of the five brave oral solution is 6.0.
Embodiment 2
The brave oral solution of one kind five, raw material contain the component of following parts by weight: 150 parts of Radix Angelicae Sinensis, 150 parts of safflower, 150
The Rhizoma Arisaematis (processed) of part, 150 parts of radix saposhnikoviae, 104 parts of the root of Dahurain angelica, 5 parts of Tween-80,3 parts of steviol glycoside, 2 parts of pyrosulfurous acid
Sodium, 6 parts of mosatil.The pH of the five brave oral solution is 4.0.
Embodiment 3
The brave oral solution of one kind five, raw material contain the component of following parts by weight: 128 parts of Radix Angelicae Sinensis, 128 parts of safflower, 128
The Rhizoma Arisaematis (processed) of part, 128 parts of radix saposhnikoviae, 88 parts of the root of Dahurain angelica, 3 parts of Tween-80,1 part of steviol glycoside, 1 part of pyrosulfurous acid
Sodium, 2 parts of mosatil.The pH of the five brave oral solution is 5.0.
Embodiment 4
The brave oral solution of one kind five, include following components so that its raw material in terms of 1000mL oral solution is made: 150g Radix Angelicae Sinensis, 150g are red
Flower, 150g Rhizoma Arisaematis (processed), 150g radix saposhnikoviae, the 104g root of Dahurain angelica, the Tween-80 of 5g, the steviol glycoside of 3g, the sodium pyrosulfite of 2g, 6g
Mosatil.The pH of the five brave oral solution is 4.0.
Embodiment 5
The brave oral solution of one kind five, include following components so that its raw material in terms of 1000mL oral solution is made: 100g Radix Angelicae Sinensis, 100g are red
Flower, 100g Rhizoma Arisaematis (processed), 100g radix saposhnikoviae, the 68g root of Dahurain angelica, the Tween-80 of 1g, the steviol glycoside of 0.5g, 0.3g sodium pyrosulfite,
The mosatil of 1g.The pH of the five brave oral solution is 6.0.
Embodiment 6
The brave oral solution of one kind five, include following components so that its raw material in terms of 1000mL oral solution is made: 128g Radix Angelicae Sinensis, 128g are red
Flower, 128g Rhizoma Arisaematis (processed), 128g radix saposhnikoviae, the 88g root of Dahurain angelica, 3g Tween-80,1g steviol glycoside, the sodium pyrosulfite of 1g, 2g according to ground
Sour calcium sodium.The pH of the five brave oral solution is 5.0.
Embodiment 7
The present embodiment provides the preparation methods of described in embodiment 6 five brave oral solutions, to be made in terms of 1000mL oral solution, including
Following steps:
1) by formula weigh required raw material (i.e. Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed), the root of Dahurain angelica, Tween-80, steviol glycoside,
Sodium pyrosulfite, mosatil)；
2) after mixing Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica, adding the concentration of 8 times of weight is 70% ethyl alcohol, is returned
Stream extracts 3 times, 2 hours every time, filters, merging filtrate by several times, recycles ethyl alcohol；Relative density 1.07 (50 DEG C) are concentrated under reduced pressure into,
Concentrate is obtained, is put to room temperature；
3) clarify: it is -1% acetum 60mL of 2% chitosan that mass concentration is added into gained concentrate, is sufficiently stirred
It mixes, is heated to 60 DEG C of heat preservation 10min, put to room temperature, filtering obtains clarified solution；
4) the edible alcohol 167mL that volumetric concentration is 60% is then added into clarified solution, stirs evenly；Medical fluid weight is added
The diatomite of amount 1%, is stirred evenly and is filtered using plate filter, and filtrate is collected；
5) Tween-80, steviol glycoside, sodium pyrosulfite, mosatil is added by formula, stirs evenly；Purifying is added
Water is settled to 1000mL, and adjusting pH value is 5.0, is stirred evenly, and filters；
6) filling, every filling 10mL, 100 DEG C sterilizing about 30 minutes to get.
The brave oral solution of the present embodiment five recommends dose are as follows: each 10mL, 2 times a day.
Embodiment 8
The present embodiment provides the preparation methods of described in embodiment 5 five brave oral solutions, to be made in terms of 1000mL oral solution, including
Following steps:
1) required raw material is weighed by formula；
2) after mixing Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica, adding the concentration of 10 times of weight is 60% ethyl alcohol, is returned
Stream extracts 3 times, 1 hour every time, filters, merging filtrate by several times, recycles ethyl alcohol；Relative density 1.02 (50 DEG C) are concentrated under reduced pressure into,
Concentrate is obtained, is put to room temperature；
3) clarify: it is -1% acetum 80mL of 2% chitosan that mass concentration is added into gained concentrate, is sufficiently stirred
It mixes, is heated to 60 DEG C of heat preservation 10min, put to room temperature, filtering obtains clarified solution；
4) the edible alcohol 150mL that volumetric concentration is 60% is then added into clarified solution, stirs evenly；Medical fluid weight is added
The diatomite of amount 3%, is stirred evenly and is filtered using plate filter, and filtrate is collected；
5) Tween-80, steviol glycoside, sodium pyrosulfite, mosatil is added by formula, stirs evenly；Purifying is added
Water is settled to 1000mL, adjusts pH value, stirs evenly, and filters；
6) filling, every filling 10mL, 121 DEG C sterilizing about 10 minutes to get.
The brave oral solution of the present embodiment five recommends dose are as follows: each 12.8mL, 2 times a day.
Embodiment 9
The present embodiment provides the preparation methods of described in embodiment 4 five brave oral solutions, to be made in terms of 1000mL oral solution, including
Following steps:
1) required raw material is weighed by formula；
2) after mixing Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica, adding the concentration of 5 times of weight is 65% ethyl alcohol, is returned
Stream extracts 3 times, 2 hours every time, filters, merging filtrate by several times, recycles ethyl alcohol；Relative density 1.08 (50 DEG C) are concentrated under reduced pressure into,
Concentrate is obtained, is put to room temperature；
3) it clarifies: the 1% acetum 60mL of 2% " ZTC1+1 " clarifying agent B component being added into gained concentrate, sufficiently
Stirring, is heated to 60 DEG C of heat preservation 10min, adds the aqueous solution 30mL of 2% " ZTC1+1 " clarifying agent component A, 60 DEG C of heat preservations
10min is put to room temperature, and filtering obtains clarified solution；
4) the edible alcohol 180mL that volumetric concentration is 60% is then added, stirs evenly；The silicon of medical fluid weight 1% is added
Diatomaceous earth is stirred evenly and is filtered using plate filter, and filtrate is collected；
5) Tween-80, steviol glycoside, sodium pyrosulfite, mosatil is added by formula, stirs evenly；Purifying is added
Water is settled to 1000mL, adjusts pH value, stirs evenly, and filters；
6) filling, every filling 10mL, 100 DEG C sterilizing about 30 minutes to get.
The brave oral solution of the present embodiment five recommends dose are as follows: each 8.5mL, 2 times a day.
Comparative example 1
The brave oral solution of one kind five, includes following components so that oral solution in terms of 1000mL is made to count its raw material: 128g Radix Angelicae Sinensis, 128g
Safflower, 128g radix saposhnikoviae, 128g Rhizoma Arisaematis (processed), the 88g root of Dahurain angelica, 1g steviol glycoside.The preparation method of the five brave oral solution is to be made
1000mL oral solution meter, comprising the following steps:
1) required raw material is weighed by formula；
2) after mixing Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica, 70% alcohol reflux of concentration of 8 times of weight is added to mention
It takes 3 times, 2 hours every time, filtration, merging filtrate recycled ethyl alcohol；Relative density 1.07 (50 DEG C) are concentrated under reduced pressure into, concentrate is obtained,
It puts to room temperature；
3) clarification (using adsorption clarification): 4% egg protein suspension 60ml is added into gained concentrate, sufficiently stirs
It mixes, heating is boiled 5 minutes, is let cool；The diatomite of medical fluid weight 1% is added, stirs evenly and is filtered using plate filter,
Collect filtrate；
4) steviol glycoside is added by formula, stirs evenly；Purified water is added and is settled to 1000mL, stirs evenly, filters；
5) filling, every filling 10mL, 100 DEG C sterilizing about 30 minutes to get.
Experimental example 1
For solve ferulic acid stability the technical issues of, this experiment according to influence medicine stability principal element (resist
Oxygen agent, pH value etc.), through single factor experiment, discovery uses inflated with nitrogen, using antioxidant vitamins C, sodium hydrogensulfite, half Guang of L-
Propylhomoserin etc. is little to the stability influence of ferulic acid；Complexing agent edetic acid(EDTA) is merged using adjusting pH value, antioxidant sodium pyrosulfite
Calcium sodium has certain effect, but does not solve the stability problem of ferulic acid at all.Then square using clarification (flocculation) is changed simultaneously
After method, in fact it has surprisingly been found that solve the technical problem of asafoetide absolute acid stability.Specific experiment design is as follows.
To be made in terms of the brave oral solution of 1000mL five, preparation method includes the following steps:
1. weighing raw material by following weight ratios: 128 grams of Radix Angelicae Sinensis, 128 grams of safflower, 128 grams of Rhizoma Arisaematis (processed), radix saposhnikoviae 128 grams, it is white
88 grams of the root of Dahurian angelica；
2. the above traditional Chinese medicine of the five flavours material adds 8 times of 70% alcohol refluxs of amount to extract 3 times, 2 hours every time, filters by several times, merge filter
Liquid recycles ethyl alcohol；It is concentrated under reduced pressure into the concentrate of 730mL, is put to room temperature；
3. clarifying；
Method a: 4% egg protein suspension 60ml being added into gained concentrate, is sufficiently stirred, and heating is boiled 5 minutes,
It puts to room temperature；
Or method b: -1% acetum 60ml of 2% chitosan is added into gained concentrate, is sufficiently stirred, is heated to 60
It DEG C heat preservation 10 minutes, puts to room temperature, filtering obtains clarified solution；
Or method c: the 1% acetum 60mL of 2% " ZTC1+1 " clarifying agent B component is added into gained concentrate, fills
Divide stirring, be heated to 60 DEG C of heat preservation 10min, adds the aqueous solution 30mL of 2% " ZTC1+1 " clarifying agent component A, 60 DEG C of heat preservations
10min is put to room temperature, and filtering obtains clarified solution；
4. 60% edible distillate spirit 167ml of concentration is added into step 3. gained clarified solution, stir evenly；Medical fluid weight is added
1% diatomite, stirs evenly, and is filtered using plate filter, collects filtrate；
5. 3g Tween-80,1g steviol glycoside is added into step 4. gained filtrate；It stirs evenly；And/or
6. 1g sodium pyrosulfite (antioxidant) is added into step 5. gained medical fluid, 2g mosatil (complexing agent)；It stirs
It mixes uniformly；
7. purified water is added to 1000ml, pH value is adjusted to 5.0 with sodium hydroxide solution；It stirs evenly, filters,
8. filling, every 10ml, 100 DEG C sterilizing 30 minutes to get.
Preparing experimental group sample according to the above method, 3., 6. and 7. whether step adjusts pH value difference difference is step,
Specifically it see the table below.(in following table 7. step specifically refers to adjust pH value)
Each five tiger oral solution sample 1-12 of above-mentioned experimental group and the brave oral solution sample of comparative example 1 five are placed in high temperature (60 DEG C)
Under the conditions of carry out Acceleration study, by (research of ferulaic acid content measuring method, the Chinese medicine in five brave oral solutions such as document Tan Xiao plum
Material, 2003, (the 6th phase) background document 2) method disclosed in, respectively in the brave oral solution of the 0th, 5,10 day detection each sample five Ah
The content of Wei's acid.Testing result see the table below.
Each five brave oral solution high-temperature sample (60 DEG C) influence factor tests ferulaic acid content measurement result (unit mg/mL)
Each five brave oral solution high-temperature sample (60 DEG C) influence factor tests ferulaic acid content measurement result (unit mg/mL)
Each five brave oral solution high-temperature sample (60 DEG C) influence factor tests ferulaic acid content measurement result (unit mg/mL)
It is applied alone antioxidant and complexing agent to make moderate progress the stability of ferulic acid as can be seen from the above table, but is not obvious,
It adjusts pH value to be better than the improved stability effect of ferulic acid and antioxidant and complexing agent is applied alone.Individually change flucculation process to ferulic acid
Improved stability it is larger, respectively joint plus antioxidant and complexing agent or adjust pH value after asafoetide absolute acid stability make moderate progress again, but
Asafoetide acid degradation is still larger.After triple combination's application, ferulic acid stability problem obtains basic solution, high temperature influence factor 10
It, content declines within 5%.
4. 5. 6. 7. 8. by the brave oral solution sample of above-mentioned experimental group five 8 (preparation method includes that 1. 2. 3. b for step), experiment
The brave oral solution sample of group five 12 (preparation method includes that 1. 2. 3. c is 4. 5. 6. 7. 8. for step) and the brave oral solution sample of comparative example 1 five
Product carry out long-time stability experiment respectively, by document Tan Xiao plum etc. (research of ferulaic acid content measuring method in five brave oral solutions,
Chinese medicine, 2003, (the 6th phase) background document 2) method disclosed in, the content of ferulic acid in the brave oral solution of detection each sample five.Inspection
Surveying result see the table below.
Experimental group sample 8,12 each 3, sample batch samples are investigated 24 months through long-time stability as can be seen from the above table, Ah
There are few variations for Wei's acid content, and use content decline in the sample long-time stability investigation of traditional oral liquid and preparation method thereof preparation bright
Aobvious, 24 months long-term, content has dropped 33.8%.Illustrate that technical solution of the present invention is improving effective component asafoetide absolute acid stability side
Face effect is obvious.
2 pharmacodynamic experiment of experimental example
Experimental material drug: five brave oral solutions prepared by embodiment 7, lot number: 20131104；Five tigers prepared by comparative example 1
Oral solution, lot number: 20131101；Five tigers are scattered (Beijing TongrenTang Co., Ltd Tongrentang Pharmaceutical Factory, lot number 20130812),
Required concentration is prepared with 10% ethyl alcohol with preceding.Control group gives 10% ethanol solution of isometric(al).Aspirin, Shandong Xinhua system
The production of medicine limited liability company, lot number: 20130402.Pethidine hydrochloride, Yichang Humanwell Pharmaceutical Co., Ltd.'s production, batch
Number: 20130303.Animal: Kun Ming mice, 18-22g, half male and half female.Big white mouse, SD kind, 180-220g, half male and half female,
It is provided by Fukang Biotechnology Co., Ltd, Beijing China.
1 analgesic effect
Mouse is divided 5 by 1.1 mouse acetic acid writhing tests (being tested after embodiment 7 and the production of 1 sample of comparative example) at random
0.6% acetum 0.1ml/10g is injected intraperitoneally to 10% ethyl alcohol or after drug 1 hour in group, stomach-filling, observes mouse at 20 points
Writhing number in clock, the results are shown in Table 1.
The analgesic activity of the brave oral solution of 1 acetic acid writhing test of table measurement five
| Group | Dosage (g/kg) | Number of animals | Mouse writhing number |
| Normal control | 0 | 10 | 28.8±4.57 |
| Pethidine hydrochloride | 0.05 | 10 | 11.9±3.46# |
| Five tigers dissipate | 6 | 10 | 19.9±3.51# |
| Five brave oral solutions (comparative example 1) | 6 | 10 | 16.4±3.56# |
| Five brave oral solutions (embodiment 7) | 6 | 10 | 15.6±2.63# |
| Five brave oral solutions (background document 1) | 6 | 10 | 16.7±3.97# |
Note: #P < 0.01 (compared with Normal group)
The result shows that five tigers, which dissipate, can reduce mouse writhing number with each five brave oral solutions, and compared with Normal group, tool
It is statistically significant.
1.2 mouse acetic acid writhing tests (embodiment 7 and 1 sample of comparative example are tested after producing 1 year) divide mouse at random
5 groups, 0.6% acetum 0.1ml/10g is injected intraperitoneally to 10% ethyl alcohol or after drug 1 hour in stomach-filling, observes mouse at 20 points
Writhing number in clock, the results are shown in Table 2.
Analgesic activity of 2 acetic acid writhing test of the table measurement five after brave oral solution placement 1 year
| Group | Dosage (g/kg) | Number of animals | Mouse writhing number |
| Normal control | 0 | 10 | 27.5±3.62 |
| Pethidine hydrochloride | 0.05 | 10 | 12.1±3.59# |
| Five tigers dissipate | 6 | 10 | 19.6±3.72# |
| Five brave oral solutions (comparative example 1) | 6 | 10 | 21.9±3.19# |
| Five brave oral solutions (embodiment 7) | 6 | 10 | 15.9±2.97# |
Note: #P < 0.01 (compared with Normal group)
The result shows that sample, after placing 1 year, five brave oral solutions (embodiment 7) organize drug effect and are not apparent from reduction, but five tigers
Oral solution (comparative example 1) drug effect reduces obviously, but the two has statistical significance compared with Normal group.
2, anti-inflammatory effect
2.1 mouse ear caused by dimethylbenzene xylene inflammation methods
2.1.1 five brave oral solution paraxylene cause mouse ear inflammatory effect (after embodiment 7 and the production of 1 sample of comparative example
It is tested)
Mouse divides 5 groups at random, causes 45 minutes 10% ethyl alcohol of stomach-filling or drug before inflammation, and 0.05ml dimethylbenzene is applied to the mouse right side
Ear front and rear sides, another ear compare.20 minutes execution mouse, cut two ears along auricle base line, with the punch of diameter 8mm in
Auricle, weighing are laid in same position respectively, are 100g with left ear weight, calculate auris dextra inflammation percentage weight increase, the results are shown in Table 3.
The brave oral solution anti-inflammatory effect of table 3 five
| Group | Dosage (g/kg) | Number of animals | Control | Cause scorching ear weight gain % |
| Normal control | 0 | 10 | 100.0 | 159.6±34.2 |
| Aspirin | 0.1 | 10 | 100.0 | 95.70±39.5* |
| Five tigers dissipate | 6 | 10 | 100.0 | 105.3±45.7* |
| Five brave oral solutions (comparative example 1) | 6 | 10 | 100.0 | 100.4±55.3* |
| Five brave oral solutions (embodiment 7) | 6 | 10 | 100.0 | 99.5±58.2* |
| Five brave oral solutions (background document 1) | 6 | 10 | 100.0 | 100.3±61.4* |
Note: P < 0.01 * (compared with Normal group)
The result shows that five tigers dissipate and each oral solution can inhibit mice caused by dimethylbenzene xylene ear inflammation.
2.1.2 five brave oral solution paraxylene cause mouse ear inflammatory effect (embodiment 7 and 1 sample of comparative example production one
It is tested after year)
Mouse divides 5 groups at random, causes 45 minutes 10% ethyl alcohol of stomach-filling or drug before inflammation, and 0.05ml dimethylbenzene is applied to the mouse right side
Ear front and rear sides, another ear compare.20 minutes execution mouse, cut two ears along auricle base line, with the punch of diameter 8mm in
Auricle, weighing are laid in same position respectively, are 100g with left ear weight, calculate auris dextra inflammation percentage weight increase, the results are shown in Table 4.
Anti-inflammatory effect after the brave oral solution of table 4 five is placed 1 year
| Group | Dosage (g/kg) | Number of animals | Control | Cause scorching ear weight gain % |
| Normal control | 0 | 10 | 100.0 | 157.4±54.1 |
| Aspirin | 0.1 | 10 | 100.0 | 96.35±42.8* |
| Five tigers dissipate | 6 | 10 | 100.0 | 104.6±41.4* |
| Five brave oral solutions (comparative example 1) | 6 | 10 | 100.0 | 121.4±47.4 |
| Five brave oral solutions (embodiment 7) | 6 | 10 | 100.0 | 100.3±46.3* |
Note: P < 0.01 * (compared with Normal group)
It is and normal the result shows that sample, after placing 1 year, five brave oral solutions (embodiment 7) organize drug effects and are not apparent from reduction
Control group compares, and has statistical significance.But five brave oral solution (comparative example 1) drug effects are substantially reduced.
3.1 rat paw egg white cause scorching method (being tested after embodiment 7 and the production of 1 sample of comparative example)
On rat egg white, swollen influence rat divides 5 groups to five brave oral solutions at random enough, every group 9, gavages before every rat is tested
Light water 5ml, stomach-filling is subcutaneous by egg white 0.05ml injection rat hindleg plantar to 10% ethyl alcohol or after drug 15 minutes, before causing inflammation
And cause 0.5,1.0,2.0,4.0,6.0 hour measurement rat paw volume after inflammation, calculate volume change percentage, it the results are shown in Table
5。
The brave oral solution of table 5 five causes the influence of rat paw edema to egg white
* P < 0.01 the * * of P < 0.05 (compared with Normal group) Δ P < 0.05:(is compared with the scattered group of five tigers)
The result shows that each administration group rat paw edema degree is significantly lower than Normal group, it is statistically analyzed, In
At each moment after albumen injection, in addition to five tigers are dispersed in 0.5 hour, each administration group has a significant difference compared with the control group, and five
Tiger dissipates compared with each five brave oral solution groups, and significant in 0.5 hour swelling degree difference, other each moment indifferences illustrate five
Brave oral solution and five tigers, which dissipate, has an obvious inhibiting effect to rat egg white arthritis, but five tiger's jaws take five tiger of liquor ratio dissipate it is rapid-action.
3.2 rat paw egg white cause scorching method (embodiment 7 and 1 sample of comparative example are tested after producing 1 year)
On rat egg white, swollen influence rat divides 5 groups to five brave oral solutions at random enough, every group 9, gavages before every rat is tested
Light water 5ml, stomach-filling is subcutaneous by egg white 0.05ml injection rat hindleg plantar to 10% ethyl alcohol or after drug 15 minutes, before causing inflammation
And cause 0.5,1.0,2.0,4.0,6.0 hour measurement rat paw volume after inflammation, calculate volume change percentage, it the results are shown in Table
6。
The brave oral solution of table 6 five causes the influence of rat paw edema to egg white after placing 1 year
* P < 0.01 the * * of P < 0.05 (compared with Normal group) Δ P < 0.05:(is compared with the scattered group of five tigers)
The result shows that five brave oral solutions (embodiment 7) are swollen at 0.5 hour compared with the scattered group of five tigers after sample is placed 1 year
Swollen degree difference is significant, other each moment indifferences；Five brave oral solutions (comparative example 1) are compared with the scattered group of five tigers, each moment
Indifference illustrates that sample places Nian Houwu tiger oral solution (embodiment 7) drug effect without reduction, and five brave oral solutions (comparative example 1)
Drug effect reduces, suitable with the scattered drug effect of five tigers.
To sum up, five brave oral solutions (embodiment 7) 0 month when drug effect and five brave oral solutions (comparative example 1) and 1 medicine of background document
No significant difference is imitated, but is dissipated better than five tigers, 1 year drug effect is placed and is better than five brave oral solutions (comparative example 1).
Clinical treatment case
The clinical verification work that five brave oral solutions (embodiment 7) treat acute soft tissue injury has been carried out in 3 hospitals, and
It dissipates and is compareed with five tigers.Treatment group 35.Clinical recovery 17, effective 11.Effective 6, invalid 1, total effective rate
97.14%, cure-remarkable-effectiveness rate 80.00%；It is control group 33, clinical recovery 6, effective 8, effective 17, invalid 2, total effective
Rate 90.39%, cure-remarkable-effectiveness rate 42.42%；Two groups of curative effects are examined through Ridit, there is significant (P < 0.01).As a result it see the table below.
The brave oral solution therapeutic effect of table five
| Group | Number of cases | Recovery from illness | It is effective | Effectively | In vain | Total effective rate |
| Treatment group | 35 | 17 | 11 | 6 | 1 | 97.14 |
| Control group | 33 | 6 | 8 | 17 | 2 | 90.39 |
Two groups of comparison among groups P < 0.01, difference are statistically significant.
This observation result also shows that five brave oral solutions (embodiment 7) are under observed case and observation dosage without bad anti-
Should and toxic side effect.
To sum up, five brave oral solutions (embodiment 7) can obviously improve the clinical symptoms such as pain, swelling, ecchymosis, dysfunction.
It dissipates and compares with five tigers, with convenient to take, patient is easy to receive, rapid-action, eutherapeutic feature.
3 long-time stability stability experiment of experimental example
According to " Chinese Pharmacopoeia " 2010 editions medicine stability guidelines, to the three batches of (lot numbers of brave oral solution of embodiment 7 five
20140101,20140102,20140103) sample progress long-time stability investigation, investigate project are as follows: character, identification, clarification
Degree, relative density, pH value, amount of alcohol, content, microbial limit etc..
In three batches by sample, it is placed under conditions of 25 ± 2 DEG C of temperature, sampled one respectively at 0,3,6,9,12,18 month
It is secondary, by stability high spot reviews item detection, compared with 0 month, as a result see the table below shown in 3-1,3-2 and 3-3.
Three batch datas the result shows that: test sample by 18 months long-time stability investigate, investigated project do not have show
The variation of work property, indices meet regulation, illustrate that five brave oral solutions have preferable stability, validity period can fix tentatively 18 months.
The brave oral solution long-term stable experiment inspection result (lot number 20140101) of table 3-1 five
The brave oral solution long-term stable experiment inspection result (lot number 20140102) of table 3-2 five
The brave oral solution long-term stable experiment inspection result (lot number 20140103) of table 3-3 five
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, fall within the scope of the claimed invention without departing from theon the basis of the spirit of the present invention.
Claims (11)
1. the brave oral solution of one kind five, is made of the raw material for including following parts by weight: 100-150 parts of Radix Angelicae Sinensis, 100-150 parts red
Flower, 100-150 parts of Rhizoma Arisaematis (processed), 100-150 parts of radix saposhnikoviae, 68-104 parts of the root of Dahurain angelica, 1-5 parts of Tween-80,0.5-3 parts
Steviol glycoside, 0.3-2 parts of sodium pyrosulfite, 1-6 parts of mosatil；The five tiger oral solution pH is 4.0-6.0；
The preparation method of described five brave oral solutions, comprising the following steps:
1) required raw material is weighed by formula；
2) after mixing Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica, adding the concentration of 5-10 times of weight is 60%-70% second
Alcohol, refluxing extraction 1-3 times is 1-2 hours each, filters by several times, merging filtrate, recycles ethyl alcohol；It is concentrated under reduced pressure into relative density
1.02-1.08 obtains concentrate；
3) concentrate obtained by step 2) is clarified using chitosan or " ZTC1+1 " clarifying agent, filters to obtain clarified solution；
4) edible alcohol is added into clarified solution obtained by step 3), makes alcoholic strength to 7%-12%, stirs evenly；Filtering is collected
Filtrate；
5) Tween-80, steviol glycoside, sodium pyrosulfite, mosatil, stirring is added by formula into filtrate obtained by step 4)
Uniformly；Purified water constant volume is added, adjusts pH value, stirs evenly, filters；
6) filling, sterilizing to get.
2. according to claim 1 five brave oral solutions, which is characterized in that be made of the raw material for including following parts by weight: 128
Radix Angelicae Sinensis, 128 parts of the safflower, 128 parts of radix saposhnikoviae, 128 parts of Rhizoma Arisaematis (processed), 88 parts of the root of Dahurain angelica, 3 parts of Tween-80,1 part of part
Steviol glycoside, 1 part of sodium pyrosulfite, 2 parts of mosatil.
3. five brave oral solutions according to claim 1, which is characterized in that it is made in terms of 1000mL oral solution by including such as
Under raw material be made: 100-150g Radix Angelicae Sinensis, 100-150g safflower, 100-150g radix saposhnikoviae, 100-150g Rhizoma Arisaematis (processed), 68-104g
The root of Dahurain angelica, 1-5g Tween-80,0.5-3g steviol glycoside, the sodium pyrosulfite of 0.3-2g, 1-6g mosatil.
4. according to claim 1 five brave oral solutions, which is characterized in that count it by including so that oral solution in terms of 1000mL is made
Following raw material is made: 128g Radix Angelicae Sinensis, 128g safflower, 128g radix saposhnikoviae, 128g Rhizoma Arisaematis (processed), the 88g root of Dahurain angelica, the Tween-80 of 3g, 1g
Steviol glycoside, the sodium pyrosulfite of 1g, 2g mosatil.
5. according to claim 1-4 five brave oral solutions, which is characterized in that the five tiger oral solution pH is 5.0.
6. the preparation method of the brave oral solution of any one of claim 1-5 described five, which comprises the following steps:
1) required raw material is weighed by formula；
2) after mixing Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed) and the root of Dahurain angelica, adding the concentration of 5-10 times of weight is 60%-70% second
Alcohol, refluxing extraction 1-3 times is 1-2 hours each, filters by several times, merging filtrate, recycles ethyl alcohol；It is concentrated under reduced pressure into relative density
1.02-1.08 obtains concentrate；
3) concentrate obtained by step 2) is clarified using chitosan or " ZTC1+1 " clarifying agent, filters to obtain clarified solution；
4) edible alcohol is added into clarified solution obtained by step 3), makes alcoholic strength to 7%-12%, stirs evenly；Filtering is collected
Filtrate；
5) Tween-80, steviol glycoside, sodium pyrosulfite, mosatil, stirring is added by formula into filtrate obtained by step 4)
Uniformly；Purified water constant volume is added, adjusts pH value, stirs evenly, filters；
6) filling, sterilizing to get.
7. preparation method according to claim 6, which is characterized in that step 2) is by Radix Angelicae Sinensis, safflower, radix saposhnikoviae, Rhizoma Arisaematis (processed)
After root of Dahurain angelica mixing, adding the concentration of 8 times of weight is 70% ethyl alcohol, refluxing extraction 3 times, 2 hours every time, filters by several times, merges filter
Liquid recycles ethyl alcohol；It is concentrated under reduced pressure into relative density 1.07, obtains concentrate, is put to room temperature.
8. preparation method according to claim 6 or 7, which is characterized in that step 3) is described by concentrate obtained by step 2)
Carrying out clear method using chitosan includes: that mass concentration is added into gained concentrate to be made in terms of 1000mL oral solution
It for -1% 50~100mL of acetum of 2% chitosan, is sufficiently stirred, is heated to 60-70 DEG C of heat preservation 10-30min, puts to room temperature,
Filtering, takes supernatant；Or
Step 3) is described, and concentrate obtained by step 2) is utilized the clear method of " ZTC1+1 " clarifying agent progress includes: to be made
1000mL oral solution meter the 1% 30~100mL of acetum of 2% " ZTC1+1 " B component is added into gained concentrate, sufficiently
Stirring, is heated to 60 DEG C of heat preservation 10-20min, adds the aqueous solution 15-60mL, 60 DEG C of heat preservation 10- of 2% " ZTC1+1 " component A
20min is put to room temperature, and filtering takes supernatant.
9. preparation method according to claim 6 or 7, which is characterized in that be filtered into described in step 4) after diatomite is added
It is filtered using plate filter.
10. preparation method according to claim 9, which is characterized in that the step 4) benefit after being filtered into addition diatomite
It is filtered with plate filter；The dosage of diatomite is the 1%-3% of medical fluid weight.
11. preparation method according to claim 6 or 7, which is characterized in that step 5) is additionally added pharmaceutically available auxiliary
Available additive on material and/or food.
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| CN102423311A (en) * | 2011-11-12 | 2012-04-25 | 辽宁海神联盛制药有限公司 | Sodium ozagrel injection solution and preparation method thereof |
| CN102988461A (en) * | 2012-11-02 | 2013-03-27 | 山西大同大学 | Rhodiola rosea injection and preparation method thereof |
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