CN105663520A - Wuhu oral liquid and preparing method thereof - Google Patents
Wuhu oral liquid and preparing method thereof Download PDFInfo
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- CN105663520A CN105663520A CN201610113641.7A CN201610113641A CN105663520A CN 105663520 A CN105663520 A CN 105663520A CN 201610113641 A CN201610113641 A CN 201610113641A CN 105663520 A CN105663520 A CN 105663520A
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- oral liquid
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- radix angelicae
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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)
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- 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
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- 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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- 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
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Abstract
The invention relates to Wuhu oral liquid and a preparing method thereof. The Wuhhu oral liquid is prepared from the following raw materials in parts by weight: 100-150 parts of Chinese angelica, 100-150 parts of safflower, 100-150 parts of prepared rhizoma arisaematis, 100-150 parts of radices sileris, 68-104 parts of radix angelicae, 1-5 parts of tween-80, 0.5-3 parts of stevioside, 0.3-2 parts of sodium pyrosulfite and 1-6 parts of sodium calcium edetate. The Wuhu oral liquid improves the use rate of the medicine raw materials, so that the product is enhanced in medicine effect aspects of pain killing, inflammation resisting, blood activating and stasis removing, and the product stability is improved.
Description
Technical field
The invention belongs to technical field of Chinese medicines, relate to the oral liquid being effective ingredient with Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed), Radix Angelicae Dahuricae five kinds of Chinese medicine, particularly a kind of five tiger oral liquids and preparation method thereof.
Background technology
Five tigers dissipate former side and come from Qing Dynasty's " raising He Tingji side ", are the good medicine for treating traumatic injury, swelling and pain due to blood stasis, are recorded by going through version " Chinese Pharmacopoeia ". It is powder owing to five tigers dissipate former side. Powder is very fast relative to pill onset, but the relatively modern dosage form such as quick-acting is then relatively slow, exist in-convenience in use, poor bioavailability, the quality of the pharmaceutical preparations such as is difficult to control at the weak point. Oral liquid absorbs fast than pill and powder, good compared with tincture mouthfeel, zest is little.
Five tiger oral liquids are based in " Chinese Pharmacopoeia " five tigers and dissipate prescriptions carrying out the new drug of form improvement development. (the drug efficacy study of five tiger oral liquids such as Deng Hongzhu, No.1 Military Medical Univ.'s journal, publication date: 2000, issue: the 3rd phase, call background document 1 in the following text) disclose the pain stop and anti-inflammation effect of five tiger oral liquids and on the hemorheological impact of animal model with blood stasis. Result shows, no matter oral liquid or powder all has obvious pain relieving, antiinflammatory action, and whole blood viscosity and the HCT of rat's blood stasis model can be reduced, but oral liquid compared with powder in pain stop and anti-inflammation rapid-action, except curative effect relatively powder improves, oral liquid also overcomes powder and also exists and take inconvenience, absorb poor, and Hygienic Index is difficult to reach the weak point such as requirement, difficult quality control. Tan Xiaomei etc. (research of ferulaic acid content assay method in five tiger oral liquids, Chinese crude drug, 2003, (the 6th phase), call background document 2 in the following text) disclose the content assaying method of the effective ingredient ferulic acid of monarch drug Radix Angelicae Sinensis in five tiger oral liquids. Method: adopt high performance liquid chromatography, chromatographic column: C18 post (125 × 4mm, 5 μm); Mobile phase: methanol-1% acetic acid (24: 76); Theoretical cam curve is not less than 1500 in ferulic acid; Detection wavelength: 313nm. result: the range of linearity of ferulaic acid content is 0.11～0.385 μ g, r=0.9999, and mean sample recovery rate is 100.79%, RSD=1.87%. The method is simple and reliable, it is easy to operation, sensitive, accurate, and specificity is strong, favorable reproducibility, can be used for the mensuration of ferulaic acid content in five tiger oral liquids and quality control.
But the consumption of the unexposed five tiger each medical materials of oral liquid of background document 1 and preparation technology, also its adjuvant used unexposed. Research finds, five tiger oral liquids prepared by traditional method exist the weakness that in pharmacy procedure, effective ingredient runs off, and drug effect is not good, especially active component ferulic acid less stable, easily occurs that content declines, and limit the popularization and application of five tiger oral liquids.
Summary of the invention
The purpose of the present invention is intended to overcome existing five tigers to dissipate the drawbacks described above existed, it is provided that a kind of five tiger oral liquids and preparation method thereof, and this five tigers oral liquid is the oral liquid of a kind of pure Chinese medicine combination, the effects such as this product has blood circulation promoting and blood stasis dispelling, reducing swelling and alleviating pain. For the disease such as treat traumatic injury, swelling and pain due to blood stasis, sprain. This product has the advantages such as taking dose is little, mouthfeel good, taking convenience, absorption is very fast, onset is rapid, bioavailability is high, effective ingredient ferulic acid steady quality, production technology are simple.
Realize the object of the invention technical scheme as follows:
A kind of five tiger oral liquids, its raw material contains the component of following weight portion: the Radix Angelicae Sinensis of 100-150 part, the Flos Carthami of 100-150 part, the Radix Saposhnikoviae of 100-150 part, the Rhizoma Arisaematis (processed) of 100-150 part, the Radix Angelicae Dahuricae of 68-104 part, the tween 80 of 1-5 part, the stevioside of 0.5-3 part, the sodium pyrosulfite of 0.3-2 part, 1-6 part calcium disodium edetate.
Preferably, described five tiger oral liquids, its raw material contains the component of following weight portion: the Radix Angelicae Sinensis of 128 parts, the Flos Carthami of 128 parts, the Radix Saposhnikoviae of 128 parts, the Rhizoma Arisaematis (processed) of 128 parts, the Radix Angelicae Dahuricae of 88 parts, the tween 80 of 3 parts, the stevioside of 1 part, the sodium pyrosulfite of 1 part, the calcium disodium edetate of 2 parts.
Further preferably, five tiger oral liquids of the present invention, include following components making its raw material of 1000mL oral liquid: 100-150g Radix Angelicae Sinensis, 100-150g Flos Carthami, 100-150g Radix Saposhnikoviae, 100-150g Rhizoma Arisaematis (processed), the 68-104g Radix Angelicae Dahuricae, 1-5g tween 80,0.5-3g stevioside, the sodium pyrosulfite of 0.3-2g, 1-6g calcium disodium edetate.
Preferably, described five tiger oral liquids, count its raw material and include following components making 1000mL oral liquid: 128g Radix Angelicae Sinensis, 128g Flos Carthami, 128g Radix Saposhnikoviae, 128g Rhizoma Arisaematis (processed), the 88g Radix Angelicae Dahuricae, the tween 80 of 3g, the stevioside of 1g, the sodium pyrosulfite of 1g, 2g calcium disodium edetate.
Preferably, described five tiger oral liquid pH are 4.0-6.0; It is preferred that pH is 5.0.
Weight portion of the present invention can be the unit of weights well known in the art such as μ g, mg, g, kg, it is also possible to is its multiple, such as 1/10,1/100,10 times, 100 times etc.
Do not affecting on the basis of drug effect and stability, five tiger its raw materials of oral liquid of the present invention may also include pharmaceutically can adjuvant, and/or additive available on food.
The preparation method that the present invention also provides for above-mentioned five tiger oral liquids, comprises the following steps:
1) needed raw material (i.e. Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed), the Radix Angelicae Dahuricae, tween 80, stevioside, sodium pyrosulfite, calcium disodium edetate etc.) is weighed by formula;
2) after Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae being mixed, the concentration adding 5-10 times of weight is 60%-70% ethanol, reflux, extract, 1-3 time, each 1-2 hour, and gradation filters, merging filtrate, reclaims ethanol; It is evaporated to relative density 1.02-1.08 (50-70 DEG C), obtains concentrated solution;
3) by step 2) gained concentrated solution utilizes chitosan or " ZTC1+1 " clarifier to clarify, and filters to obtain clear liquor;
4) to step 3) gained clear liquor adds edible ethanol, make alcoholic strength to 7%-12% (referring to volumetric concentration), stir; Filter, collect filtrate;
5) to step 4) gained filtrate is pressed formula add tween 80, stevioside, sodium pyrosulfite, calcium disodium edetate, stir; Add purified water constant volume, regulate pH value, stir, filter;
6) fill, sterilizing, to obtain final product.
The preparation method of above-mentioned five tiger oral liquids, wherein:
Preferably, step 2) by after the mixing of Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae, the concentration adding 8 times of weight is 70% ethanol, reflux, extract, 3 times, each 2 hours, and gradation filters, merging filtrate, reclaims ethanol; It is evaporated to relative density 1.07 (50 DEG C), obtains concentrated solution, put to room temperature.
Preferably, step 3) described by step 2) gained concentrated solution utilizes the method that chitosan carries out clarifying to include: to make 1000mL oral liquid, adding mass concentration in gained concentrated solution is 2% chitosan-1% acetum (namely solvent is the acetum of volumetric concentration 1%) 50～100mL, it is sufficiently stirred for, heat to 60-70 DEG C of insulation 10-30min, put to room temperature, filter, take supernatant; Or
Preferably, step 3) described by step 2) gained concentrated solution utilizes " ZTC1+1 " clarifier method of carrying out clarifying to include: to make 1000mL oral liquid, the 1% acetum 30～100mL of 2% " ZTC1+1 " B component is added in gained concentrated solution, it is sufficiently stirred for, heats to 60 DEG C of insulation 10-20min, add the aqueous solution 15-60mL of 2% " ZTC1+1 " component A, 60 DEG C of insulation 10-20min, put to room temperature, filter, take supernatant.
Chitosan clarifier of the present invention can adopt commercial goods; Described " ZTC1+1 " clarifier is Beijing Zheng Tiancheng clarification technique company limited commercial goods product.
Preferably, step 4) described in be filtered into addition kieselguhr after utilize plate filter to filter; It is further preferred that the 1%-3% that diatomaceous consumption is medicinal liquid weight.
Preferably, step 5) can also add pharmaceutically can adjuvant, and/or additive available on food; To strengthen the stability of described oral liquid or to regulate mouthfeel; But not affect drug effect and stability for benchmark.
Preferably, step 6) sterilizing methods is that 121 DEG C of sterilizings are about 8-15min; Or 100 DEG C of sterilizings 30 minutes.
The present invention can adopt this area routine pH value regulator to regulate pH value, for instance sodium hydroxide, hydrochloric acid etc.
The present invention five tiger oral liquid recommendation dose is: 5-20mL, every day 2 times every time; Preferably each 10mL, every day 2 times.
The present invention five tiger oral liquid is based in " Chinese Pharmacopoeia " five tigers and dissipates prescriptions carrying out the new drug of form improvement development. The purposes such as taking dose is little, mouthfeel good, taking convenience, absorption is very fast, onset is rapid, bioavailability is high, effective ingredient ferulic acid steady quality, production technology is simple, product quality is easily controllable are reached after making five tiger oral liquids into.
The invention have the benefit that
The present invention five tiger oral liquid improves the utilization rate of pharmaceutical raw material, makes product drug effect in pain relieving, antiinflammatory and promoting blood circulation to remove blood stasis etc. obtain enhancing, and improves product stability.
Detailed description of the invention
Following example are used for illustrating the present invention, but are not limited to the scope of the present invention. Unreceipted concrete technology or condition person in embodiment, technology described by the document in this area or condition, or carry out according to product description. Agents useful for same or the unreceipted production firm person of instrument, be the conventional products can being commercially available by regular distributor. Wherein, chitosan clarifier is provided by Zhejiang Jin Ke pharmaceutcal corporation, Ltd; " ZTC1+1 " clarifier is provided by Beijing Zheng Tiancheng clarification technique company limited; Ovalbumin clarifier is provided by Chemical Reagent Co., Ltd., Sinopharm Group.
Embodiment 1
A kind of five tiger oral liquids, its raw material contains the component of following weight portion: the Radix Angelicae Sinensis of 100 parts, the Flos Carthami of 100 parts, the Rhizoma Arisaematis (processed) of 100 parts, the Radix Saposhnikoviae of 100 parts, the Radix Angelicae Dahuricae of 68 parts, the tween 80 of 1 part, the stevioside of 0.5 part, the sodium pyrosulfite of 0.3 part, the calcium disodium edetate of 1 part. The pH of this five tigers oral liquid is 6.0.
Embodiment 2
A kind of five tiger oral liquids, its raw material contains the component of following weight portion: the Radix Angelicae Sinensis of 150 parts, the Flos Carthami of 150 parts, the Rhizoma Arisaematis (processed) of 150 parts, the Radix Saposhnikoviae of 150 parts, the Radix Angelicae Dahuricae of 104 parts, the tween 80 of 5 parts, the stevioside of 3 parts, the sodium pyrosulfite of 2 parts, the calcium disodium edetate of 6 parts. The pH of this five tigers oral liquid is 4.0.
Embodiment 3
A kind of five tiger oral liquids, its raw material contains the component of following weight portion: the Radix Angelicae Sinensis of 128 parts, the Flos Carthami of 128 parts, the Rhizoma Arisaematis (processed) of 128 parts, the Radix Saposhnikoviae of 128 parts, the Radix Angelicae Dahuricae of 88 parts, the tween 80 of 3 parts, the stevioside of 1 part, the sodium pyrosulfite of 1 part, the calcium disodium edetate of 2 parts. The pH of this five tigers oral liquid is 5.0.
Embodiment 4
A kind of five tiger oral liquids, include following components making its raw material of 1000mL oral liquid: 150g Radix Angelicae Sinensis, 150g Flos Carthami, 150g Rhizoma Arisaematis (processed), 150g Radix Saposhnikoviae, the 104g Radix Angelicae Dahuricae, the tween 80 of 5g, the stevioside of 3g, the sodium pyrosulfite of 2g, 6g calcium disodium edetate. The pH of this five tigers oral liquid is 4.0.
Embodiment 5
A kind of five tiger oral liquids, include following components making its raw material of 1000mL oral liquid: 100g Radix Angelicae Sinensis, 100g Flos Carthami, 100g Rhizoma Arisaematis (processed), 100g Radix Saposhnikoviae, the 68g Radix Angelicae Dahuricae, the tween 80 of 1g, the stevioside of 0.5g, the sodium pyrosulfite of 0.3g, 1g calcium disodium edetate. The pH of this five tigers oral liquid is 6.0.
Embodiment 6
A kind of five tiger oral liquids, include following components making its raw material of 1000mL oral liquid: 128g Radix Angelicae Sinensis, 128g Flos Carthami, 128g Rhizoma Arisaematis (processed), 128g Radix Saposhnikoviae, the 88g Radix Angelicae Dahuricae, 3g tween 80,1g stevioside, the sodium pyrosulfite of 1g, 2g calcium disodium edetate. The pH of this five tigers oral liquid is 5.0.
Embodiment 7
The present embodiment provides the preparation method of five tiger oral liquids described in embodiment 6, to make 1000mL oral liquid, comprises the following steps:
1) by formula weigh needed raw material (namely Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed), the Radix Angelicae Dahuricae, tween 80, stevioside, sodium pyrosulfite, calcium disodium edetate);
2) after Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae being mixed, the concentration adding 8 times of weight is 70% ethanol, reflux, extract, 3 times, each 2 hours, and gradation filters, merging filtrate, reclaims ethanol; It is evaporated to relative density 1.07 (50 DEG C), obtains concentrated solution, put to room temperature;
3) clarification: adding mass concentration in gained concentrated solution is 2% chitosan-1% acetum 60mL, is sufficiently stirred for, heats to 60 DEG C of insulation 10min, puts to room temperature, filter, obtain clear liquor;
4) in clear liquor, then add the edible ethanol 167mL that volumetric concentration is 60%, stir; Add the kieselguhr of medicinal liquid weight 1%, stir and utilize plate filter to be filtered, collect filtrate;
5) add tween 80, stevioside, sodium pyrosulfite, calcium disodium edetate by formula, stir; Adding purified water and be settled to 1000mL, regulating pH value is 5.0, stirs, and filters;
6) fill, every fill 10mL, 100 DEG C of sterilizings about 30 minutes, to obtain final product.
The present embodiment five tiger oral liquid recommendation dose is: 10mL, every day 2 times every time.
Embodiment 8
The present embodiment provides the preparation method of five tiger oral liquids described in embodiment 5, to make 1000mL oral liquid, comprises the following steps:
1) needed raw material is weighed by formula;
2) after Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae being mixed, the concentration adding 10 times of weight is 60% ethanol, reflux, extract, 3 times, each 1 hour, and gradation filters, merging filtrate, reclaims ethanol; It is evaporated to relative density 1.02 (50 DEG C), obtains concentrated solution, put to room temperature;
3) clarification: adding mass concentration in gained concentrated solution is 2% chitosan-1% acetum 80mL, is sufficiently stirred for, heats to 60 DEG C of insulation 10min, puts to room temperature, filter, obtain clear liquor;
4) in clear liquor, then add the edible ethanol 150mL that volumetric concentration is 60%, stir; Add the kieselguhr of medicinal liquid weight 3%, stir and utilize plate filter to be filtered, collect filtrate;
5) add tween 80, stevioside, sodium pyrosulfite, calcium disodium edetate by formula, stir; Add purified water and be settled to 1000mL, regulate pH value, stir, filter;
6) fill, every fill 10mL, 121 DEG C of sterilizings about 10 minutes, to obtain final product.
The present embodiment five tiger oral liquid recommendation dose is: 12.8mL, every day 2 times every time.
Embodiment 9
The present embodiment provides the preparation method of five tiger oral liquids described in embodiment 4, to make 1000mL oral liquid, comprises the following steps:
1) needed raw material is weighed by formula;
2) after Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae being mixed, the concentration adding 5 times of weight is 65% ethanol, reflux, extract, 3 times, each 2 hours, and gradation filters, merging filtrate, reclaims ethanol; It is evaporated to relative density 1.08 (50 DEG C), obtains concentrated solution, put to room temperature;
3) clarification: add the 1% acetum 60mL of 2% " ZTC1+1 " clarifier B component in gained concentrated solution, it is sufficiently stirred for, heat to 60 DEG C of insulation 10min, add the aqueous solution 30mL of 2% " ZTC1+1 " clarifier component A, 60 DEG C of insulation 10min, put to room temperature, filter, obtain clear liquor;
4) it is subsequently adding the edible ethanol 180mL that volumetric concentration is 60%, stirs; Add the kieselguhr of medicinal liquid weight 1%, stir and utilize plate filter to be filtered, collect filtrate;
5) add tween 80, stevioside, sodium pyrosulfite, calcium disodium edetate by formula, stir; Add purified water and be settled to 1000mL, regulate pH value, stir, filter;
6) fill, every fill 10mL, 100 DEG C of sterilizings about 30 minutes, to obtain final product.
The present embodiment five tiger oral liquid recommendation dose is: 8.5mL, every day 2 times every time.
Comparative example 1
A kind of five tiger oral liquids, count its raw material and include following components making 1000mL oral liquid: 128g Radix Angelicae Sinensis, 128g Flos Carthami, 128g Radix Saposhnikoviae, 128g Rhizoma Arisaematis (processed), the 88g Radix Angelicae Dahuricae, 1g stevioside. The preparation method of this five tigers oral liquid, to make 1000mL oral liquid, comprises the following steps:
1) needed raw material is weighed by formula;
2) after Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae being mixed, add concentration 70% alcohol reflux 3 times of 8 times of weight, each 2 hours, filter, merging filtrate, reclaim ethanol; It is evaporated to relative density 1.07 (50 DEG C), obtains concentrated solution, put to room temperature;
3) clarification (employing adsorption clarification): add the egg protein suspension 60ml of 4% in gained concentrated solution, be sufficiently stirred for, heated and boiled 5 minutes, let cool; Add the kieselguhr of medicinal liquid weight 1%, stir and utilize plate filter to be filtered, collect filtrate;
4) add stevioside by formula, stir; Add purified water and be settled to 1000mL, stir, filter;
5) fill, every fill 10mL, 100 DEG C of sterilizings about 30 minutes, to obtain final product.
Experimental example 1
For solving the technical problem of the stability of ferulic acid, this experiment is according to the principal element (antioxidant affecting medicine stability, pH value etc.), through single factor experiment, find to adopt inflated with nitrogen, adopt antioxidant vitamins C, sodium sulfite, Cys etc. that the stability influence of ferulic acid is little; Adopt and regulate pH value, antioxidant sodium pyrosulfite merging chelating agent calcium disodium edetate has certain effect, but does not solve the stability problem of ferulic acid at all. Then adopt after changing clarification (flocculation) method, in fact it has surprisingly been found that solve the technical barrier of ferulic acid stability simultaneously. Specific experiment design is as follows.
To make 1000mL five tiger oral liquid, its preparation method comprises the following steps:
1. raw material is weighed by following weight ratio: Radix Angelicae Sinensis 128 grams, 128 grams of Flos Carthami, Rhizoma Arisaematis (processed) 128 grams, Radix Saposhnikoviae 128 grams, the Radix Angelicae Dahuricae 88 grams;
2. above Chinese medicine of the five flavours material, adds 8 times amount 70% alcohol reflux 3 times, each 2 hours, and gradation filters, merging filtrate, reclaims ethanol; It is evaporated to the concentrated solution of 730mL, puts to room temperature;
3. clarify;
Method a: add the egg protein suspension 60ml of 4% in gained concentrated solution, be sufficiently stirred for, heated and boiled 5 minutes, put to room temperature;
Or method b: in gained concentrated solution, add 2% chitosan-1% acetum 60ml, be sufficiently stirred for, heat to 60 DEG C of insulations 10 minutes, put to room temperature, filter, obtain clear liquor;
Or method c: in gained concentrated solution, add the 1% acetum 60mL of 2% " ZTC1+1 " clarifier B component, be sufficiently stirred for, heat to 60 DEG C of insulation 10min, add the aqueous solution 30mL of 2% " ZTC1+1 " clarifier component A, 60 DEG C of insulation 10min, put to room temperature, filter, obtain clear liquor;
4. in step 3. gained clear liquor, add concentration 60% edible distillate spirit 167ml, stir; Add the kieselguhr of medicinal liquid weight 1%, stir, utilize plate filter to be filtered, collect filtrate;
5. in step 4. gained filtrate, add 3g tween 80,1g stevioside; Stir; And/or
6. in step 5. gained medicinal liquid, add 1g sodium pyrosulfite (antioxidant), 2g calcium disodium edetate (chelating agent); Stir;
7. add purified water to 1000ml, regulate to pH value to 5.0 with sodium hydroxide solution; Stir, filter,
8. fill, every 10ml, 100 DEG C of sterilizings 30 minutes, to obtain final product.
Prepare experimental group sample as stated above, be distinctive in that step 3., 6. and step 7. whether regulate pH value difference, be specifically shown in following table. (in following table, 7. step specifically refers to regulate pH value)
Each for above-mentioned experimental group five tiger oral liquid sample 1-12 and comparative example 1 five tiger oral liquid sample are placed under high temperature (60 DEG C) condition and are accelerated experiment, by (researchs of ferulaic acid content assay method in five tiger oral liquids such as document Tan Xiao prunus mume (sieb.) sieb.et zucc.s, Chinese crude drug, 2003, (the 6th phase) background document 2) disclosed in method, detected the content of ferulic acid in each sample five tiger oral liquid respectively at the 0th, 5,10 days. Testing result is shown in following table.
Each five tiger oral liquid high-temperature sample (60 DEG C) influence factors test ferulaic acid content measurement result (unit mg/mL)
Each five tiger oral liquid high-temperature sample (60 DEG C) influence factors test ferulaic acid content measurement result (unit mg/mL)
Each five tiger oral liquid high-temperature sample (60 DEG C) influence factors test ferulaic acid content measurement result (unit mg/mL)
The stability of ferulic acid is made moderate progress by alone antioxidant and chelating agent as can be seen from the above table, but and inconspicuous, adjust pH value the improved stability effect of ferulic acid is better than alone antioxidant and chelating agent. Individually change flucculation process the improved stability of ferulic acid is relatively big, combine ferulic acid stability after adding antioxidant and chelating agent or adjusting pH value respectively and make moderate progress again, but ferulic acid degraded is still bigger. After triple combination's application, ferulic acid stability problem obtains basic solution, high temperature influence factor 10 days, and content declines within 5%.
By above-mentioned experimental group five tiger oral liquid sample 8 (its preparation method includes step, and 1. 2. 3. b is 4. 5. 6. 7. 8.), experimental group five tiger oral liquid sample 12 (its preparation method includes step, and 1. 2. 3. c is 4. 5. 6. 7. 8.), and comparative example 1 five tiger oral liquid sample carries out long-time stability experiment respectively, by (researchs of ferulaic acid content assay method in five tiger oral liquids such as document Tan Xiao prunus mume (sieb.) sieb.et zucc.s, Chinese crude drug, 2003, (the 6th phase) background document 2) disclosed in method, the content of ferulic acid in detection each sample five tiger oral liquid. Testing result is shown in following table.
Experimental group sample 8, each 3 batch samples of sample 12 are investigated 24 months through long-time stability as can be seen from the above table, ferulaic acid content is several unchanged, and content declines substantially in adopting sample long-time stability prepared by traditional oral liquid and preparation method thereof to investigate, long-term 24 months, content have dropped 33.8%. Illustrate that technical solution of the present invention effect in improving effective ingredient ferulic acid stability is obvious.
Experimental example 2 pharmacodynamic experiment
Experiment material medicine: five tiger oral liquids of embodiment 7 preparation, lot number: 20131104; Five tiger oral liquids of comparative example 1 preparation, lot number: 20131101; Five tigers dissipate (Tongrentang Pharmaceutical Factory, Beijing TongrenTang Co., Ltd, lot number 20130812), prepare desired concn with front with 10% ethanol. Matched group gives isometric 10% alcoholic solution. Aspirin, Shandong XinHua Pharmacy stock Co., Ltd produces, lot number: 20130402. Pethidine hydrochloride, Yichang Humanwell Pharmaceutical Co., Ltd. produces, lot number: 20130303. Animal: Kun Ming mice, 18-22g, male and female half and half. Rat, SD kind, 180-220g, male and female half and half, Fukang bio tech ltd of Beijing China provide.
1 analgesic effect
Mice is divided 5 groups by 1.1 mice acetic acid writhing test (namely embodiment 7 and comparative example 1 sample are tested after producing) at random, gavage gives 10% ethanol or medicine after 1 hour, lumbar injection 0.6% acetum 0.1ml/10g, observes the writhing number of times that mice is interior at 20 minutes, and result is in Table 1.
Table 1 acetic acid writhing test measures the analgesic activity of five tiger oral liquids
| Group | Dosage (g/kg) | Number of animals | Mouse writhing number of times |
| 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 tigers oral liquid (comparative example 1) | 6 | 10 | 16.4±3.56# |
| Five tigers oral liquid (embodiment 7) | 6 | 10 | 15.6±2.63# |
| Five tigers oral liquid (background document 1) | 6 | 10 | 16.7±3.97# |
Note: #P < 0.01 (compares with Normal group)
It is shown that five tigers dissipate all can reduce mouse writhing number of times with each five tiger oral liquids, compare with Normal group, there is statistical significance.
Mice is divided 5 groups by 1.2 mice acetic acid writhing test (embodiment 7 and comparative example 1 sample are tested after producing a year) at random, gavage gives 10% ethanol or medicine after 1 hour, lumbar injection 0.6% acetum 0.1ml/10g, observing the writhing number of times that mice is interior at 20 minutes, result is in Table 2.
Table 2 acetic acid writhing test measures the analgesic activity after five tiger oral liquids are placed a year
| Group | Dosage (g/kg) | Number of animals | Mouse writhing number of times |
| 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 tigers oral liquid (comparative example 1) | 6 | 10 | 21.9±3.19# |
| Five tigers oral liquid (embodiment 7) | 6 | 10 | 15.9±2.97# |
Note: #P < 0.01 (compares with Normal group)
It is shown that after sample is placed 1 year, five tiger oral liquids (embodiment 7) group drug effects are not apparent from reducing, but five tiger oral liquid (comparative example 1) drug effects reduce substantially, but both compare with Normal group, have statistical significance.
2, antiinflammatory action
2.1 mouse ear caused by dimethylbenzene xylene inflammation methods
2.1.1 five tiger oral liquid xylol cause mouse ear inflammatory effect (namely embodiment 7 and comparative example 1 sample are tested after producing)
Mice divides 5 groups at random, causes scorching first 45 minutes gavage 10% ethanol or medicine, 0.05ml dimethylbenzene is applied to both sides before and after mouse right ear, and another ear compares. Within 20 minutes, putting to death mice, cut two ears along auricle baseline, lay auricle with the card punch of diameter 8mm respectively in same position, weigh, with left ear weight for 100g, calculate auris dextra inflammation percentage weight increase, result is in Table 3.
Table 3 five tiger oral liquid antiinflammatory action
| Group | Dosage (g/kg) | Number of animals | Comparison | Cause scorching ear weightening finish % |
| 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 tigers oral liquid (comparative example 1) | 6 | 10 | 100.0 | 100.4±55.3* |
| Five tigers oral liquid (embodiment 7) | 6 | 10 | 100.0 | 99.5±58.2* |
| Five tigers oral liquid (background document 1) | 6 | 10 | 100.0 | 100.3±61.4* |
Note: * P < 0.01 (compares with Normal group)
It is shown that five tigers dissipate and each oral liquid all can suppress mice caused by dimethylbenzene xylene ear inflammation.
2.1.2 five tiger oral liquid xylol cause mouse ear inflammatory effect (embodiment 7 and comparative example 1 sample are tested after producing a year)
Mice divides 5 groups at random, causes scorching first 45 minutes gavage 10% ethanol or medicine, 0.05ml dimethylbenzene is applied to both sides before and after mouse right ear, and another ear compares. Within 20 minutes, putting to death mice, cut two ears along auricle baseline, lay auricle with the card punch of diameter 8mm respectively in same position, weigh, with left ear weight for 100g, calculate auris dextra inflammation percentage weight increase, result is in Table 4.
Antiinflammatory action after 1 year placed by table 4 five tiger oral liquid
| Group | Dosage (g/kg) | Number of animals | Comparison | Cause scorching ear weightening finish % |
| 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 tigers oral liquid (comparative example 1) | 6 | 10 | 100.0 | 121.4±47.4 |
| Five tigers oral liquid (embodiment 7) | 6 | 10 | 100.0 | 100.3±46.3* |
Note: * P < 0.01 (compares with Normal group)
It is shown that after sample is placed 1 year, five tiger oral liquids (embodiment 7) group drug effects are not apparent from reducing, and compare with Normal group, have statistical significance. But five tiger oral liquid (comparative example 1) drug effects substantially reduce.
3.1 rat paw Ovum Gallus domesticus album cause scorching method (namely embodiment 7 and comparative example 1 sample are tested after producing)
Five tiger oral liquids affect rat divide 5 groups at random to rat Ovum Gallus domesticus album foot are swollen, often group 9, light water 5ml is gavaged before every rat is tested, gavage gives 10% ethanol or medicine after 15 minutes, Ovum Gallus domesticus album 0.05ml is injected the rat hindleg sole of the foot subcutaneous, after causing before inflammation and causing inflammation 0.5,1.0,2.0,4.0,6.0 hours are measured rat paw volume, are calculated change in volume percentage rate, and result is in Table 5.
Ovum Gallus domesticus album is caused the impact of rat paw edema by table 5 five tiger oral liquid
* the scattered group of P < 0.05**P < 0.01 (comparing with Normal group) Δ P < 0.05:(and five tiger compares)
Result shows, each administration group rat paw edema degree is all significantly lower than Normal group, through statistical procedures, each moment after albumen injection, except being dispersed in 0.5 hour except five tigers, each administration group compares with matched group all significant difference, five tigers dissipate compares with each five tiger oral liquid groups, notable at 0.5 hour swelling degree difference, other each moment zero differences, illustrate that rat Ovum Gallus domesticus album arthritis is had obvious inhibiting effect by five tiger oral liquids and five brave dissipating, but five tiger's jaws take liquor ratio five tiger and dissipate rapid-action.
3.2 rat paw Ovum Gallus domesticus album cause scorching method (embodiment 7 and comparative example 1 sample are tested after producing a year)
Five tiger oral liquids affect rat divide 5 groups at random to rat Ovum Gallus domesticus album foot are swollen, often group 9, light water 5ml is gavaged before every rat is tested, gavage gives 10% ethanol or medicine after 15 minutes, Ovum Gallus domesticus album 0.05ml is injected the rat hindleg sole of the foot subcutaneous, after causing before inflammation and causing inflammation 0.5,1.0,2.0,4.0,6.0 hours are measured rat paw volume, are calculated change in volume percentage rate, and result is in Table 6.
The impact that Ovum Gallus domesticus album caused after 1 year rat paw edema placed by table 6 five tiger oral liquid
* the scattered group of P < 0.05**P < 0.01 (comparing with Normal group) Δ P < 0.05:(and five tiger compares)
It is shown that sample was placed after 1 year, five tigers oral liquids (embodiment 7) dissipate groups with five tigers and compare, at 0.5 hour swelling degree difference significantly, and other each moment zero differences; Five tigers oral liquid (comparative example 1) dissipate group with five tigers and compare, each moment zero difference, illustrating that sample places after 1 year five tiger oral liquid (embodiment 7) drug effects without reduction, and five tiger oral liquid (comparative example 1) drug effects reduce, to dissipate drug effects suitable with five tigers.
To sum up, drug effect during five tiger oral liquid (embodiments 7) 0 month and five tiger oral liquid (comparative example 1) and background document 1 drug effect no significant differences, but be better than five tigers and dissipate, places 1 year drug effect and be better than five brave oral liquids (comparative example 1).
Clinical treatment case
Carry out the clinical verification work of five tiger oral liquid (embodiment 7) treatment acute soft tissue injuries in 3 hospitals, and dissipate brave with five has compareed. Treatment group 35 example. Clinical recovery 17 example, effective 11 examples. Effective 6 examples, invalid 1 example, total effective rate 97.14%, cure-remarkable-effectiveness rate 80.00%; Matched group 33 example, clinical recovery 6 example, effective 8 examples, effective 17 examples, invalid 2 examples, total effective rate 90.39%, cure-remarkable-effectiveness rate 42.42%; Two groups of curative effects are checked through Ridit, have significant (P < 0.01). Result is shown in following table.
Table five tiger oral liquid therapeutical effect
| Group | Number of cases | Recovery from illness | Effective | Effectively | Invalid | Total effective rate |
| Treatment group | 35 | 17 | 11 | 6 | 1 | 97.14 |
| Matched group | 33 | 6 | 8 | 17 | 2 | 90.39 |
Comparing P < 0.01 between two groups of groups, difference is statistically significant.
This observed result also shows, five tigers oral liquid (embodiment 7) have no adverse reaction and toxic and side effects under observed case and observation dosage.
To sum up, five tigers oral liquid (embodiment 7) can obviously improve the clinical symptoms such as pain, swelling, ecchymosis, dysfunction. Dissipating with five tigers and compare, have taking convenience, patient is prone to accept, rapid-action, eutherapeutic feature.
Experimental example 3 long-time stability stability experiment
According to " Chinese Pharmacopoeia " 2010 editions medicine stability guidelines, embodiment 7 five tiger oral liquid three batches (lot number 20140101,20140102,20140103) sample is carried out long-time stability investigation, and investigation project is: character, discriminating, clarity, relative density, pH value, amount of alcohol, content, microbial limit etc.
By sample in three batches, placing when temperature 25 ± 2 DEG C, respectively at sampling in 0,3,6,9,12,18 months once, detect by stability high spot reviews project, compared with 0 month, result is shown in shown in table 3 below-1,3-2 and 3-3.
Three batch data results show: test sample is investigated through the long-time stability of 18 months, and institute's investigation project does not all have significance to change, and indices meets regulation, illustrate that five tiger oral liquids have good stability, and effect duration can fix tentatively 18 months.
Table 3-1 five tiger oral liquid long-term stable experiment assay (lot number 20140101)
Table 3-2 five tiger oral liquid long-term stable experiment assay (lot number 20140102)
Table 3-3 five tiger oral liquid long-term stable experiment assay (lot number 20140103)
Although, above the present invention is described in detail with a general description of the specific embodiments, but on basis of the present invention, it is possible to it is made some modifications or improvements, and this will be apparent to those skilled in the art. Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to the scope of protection of present invention.
Claims (10)
1. five tiger an oral liquid, its raw material contains the component of following weight portion: the Radix Angelicae Sinensis of 100-150 part, the Flos Carthami of 100-150 part, the Rhizoma Arisaematis (processed) of 100-150 part, the Radix Saposhnikoviae of 100-150 part, the Radix Angelicae Dahuricae of 68-104 part, the tween 80 of 1-5 part, the stevioside of 0.5-3 part, the sodium pyrosulfite of 0.3-2 part, 1-6 part calcium disodium edetate; Described five tiger oral liquid pH are 4.0-6.0.
2. five tiger oral liquids according to claim 1, it is characterized in that, its raw material contains the component of following weight portion: the Radix Angelicae Sinensis of 128 parts, the Flos Carthami of 128 parts, the Radix Saposhnikoviae of 128 parts, the Rhizoma Arisaematis (processed) of 128 parts, the Radix Angelicae Dahuricae of 88 parts, the tween 80 of 3 parts, the stevioside of 1 part, the sodium pyrosulfite of 1 part, the calcium disodium edetate of 2 parts.
3. five tiger oral liquids according to claim 1, it is characterized in that, include following components making its raw material of 1000mL oral liquid: 100-150g Radix Angelicae Sinensis, 100-150g Flos Carthami, 100-150g Radix Saposhnikoviae, 100-150g Rhizoma Arisaematis (processed), the 68-104g Radix Angelicae Dahuricae, 1-5g tween 80,0.5-3g stevioside, the sodium pyrosulfite of 0.3-2g, 1-6g calcium disodium edetate.
4. five tiger oral liquids according to claim 1, it is characterized in that, count its raw material and include following components making 1000mL oral liquid: 128g Radix Angelicae Sinensis, 128g Flos Carthami, 128g Radix Saposhnikoviae, 128g Rhizoma Arisaematis (processed), the 88g Radix Angelicae Dahuricae, the tween 80 of 3g, the stevioside of 1g, the sodium pyrosulfite of 1g, 2g calcium disodium edetate.
5. five tiger oral liquids according to any one of claim 1-4, it is characterised in that described five tiger oral liquid pH are 5.0.
6. the preparation method of five tiger oral liquids described in any one of claim 1-5, it is characterised in that comprise the following steps:
1) needed raw material is weighed by formula;
2) after Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae being mixed, the concentration adding 5-10 times of weight is 60%-70% ethanol, reflux, extract, 1-3 time, each 1-2 hour, and gradation filters, merging filtrate, reclaims ethanol; It is evaporated to relative density 1.02-1.08, obtains concentrated solution;
3) by step 2) gained concentrated solution utilizes chitosan or " ZTC1+1 " clarifier to clarify, and filters to obtain clear liquor;
4) to step 3) gained clear liquor adds edible ethanol, make alcoholic strength to 7%-12%, stir; Filter, collect filtrate;
5) to step 4) gained filtrate is pressed formula add tween 80, stevioside, sodium pyrosulfite, calcium disodium edetate, stir; Add purified water constant volume, regulate pH value, stir, filter;
6) fill, sterilizing, to obtain final product.
7. preparation method according to claim 6, it is characterised in that step 2) by after the mixing of Radix Angelicae Sinensis, Flos Carthami, Radix Saposhnikoviae, Rhizoma Arisaematis (processed) and the Radix Angelicae Dahuricae, the concentration adding 8 times of weight is 70% ethanol, reflux, extract, 3 times, each 2 hours, gradation filters, merging filtrate, reclaims ethanol; It is evaporated to relative density 1.07, obtains concentrated solution, put to room temperature.
8. the preparation method according to claim 6 or 7, it is characterized in that, step 3) described by step 2) gained concentrated solution utilizes the method that chitosan carries out clarifying to include: to make 1000mL oral liquid, adding mass concentration in gained concentrated solution is 2% chitosan-1% acetum 50～100mL, it is sufficiently stirred for, heats to 60-70 DEG C of insulation 10-30min, put to room temperature, filter, take supernatant; Or
Step 3) described by step 2) gained concentrated solution utilizes " ZTC1+1 " clarifier method of carrying out clarifying to include: to make 1000mL oral liquid, the 1% acetum 30～100mL of 2% " ZTC1+1 " B component is added in gained concentrated solution, it is sufficiently stirred for, heat to 60 DEG C of insulation 10-20min, add the aqueous solution 15-60mL of 2% " ZTC1+1 " component A, 60 DEG C of insulation 10-20min, put to room temperature, filter, take supernatant.
9. the preparation method according to claim 6 or 7, it is characterised in that step 4) described in be filtered into addition kieselguhr after utilize plate filter to filter; Preferably, diatomaceous consumption is the 1%-3% of medicinal liquid weight.
10. the preparation method according to claim 6 or 7, it is characterised in that step 5) be additionally added pharmaceutically can adjuvant, and/or additive available on food.
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