CN107898898A - End attached soft capsule and its production method and application - Google Patents

End attached soft capsule and its production method and application Download PDF

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Publication number
CN107898898A
CN107898898A CN201711401803.8A CN201711401803A CN107898898A CN 107898898 A CN107898898 A CN 107898898A CN 201711401803 A CN201711401803 A CN 201711401803A CN 107898898 A CN107898898 A CN 107898898A
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soft capsule
group
filtrate
filter residue
obtains
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CN107898898B (en
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王健
杨海燕
宋汉敏
李振国
张壮丽
李海燕
李逢春
王莉
张竞
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Henan Food And Drug Inspection Institute
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Henan Food And Drug Inspection Institute
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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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
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    • 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
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    • A61K36/185—Magnoliopsida (dicotyledons)
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    • A61K36/185—Magnoliopsida (dicotyledons)
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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    • 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)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/754—Evodia
    • A—HUMAN NECESSITIES
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • 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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Abstract

The present invention relates to a kind of production method for the attached soft capsule that ends：1）Volatile oil is extracted, obtains total volatile oil, filter residue 1 and filtrate 1；2）Water-soluble position is extracted, obtains filter residue 2 and filtrate 2；Filtrate 1 and filtrate 2 are mixed, is dried in vacuo after normal heating concentration, obtains medicinal extract 1；3）Extract the molten position of alcohol：Filter residue 1 is mixed with filter residue 2, handles, obtains medicinal extract 2；Medicinal extract 1 and medicinal extract 2 are denoted as extract powder；4）Soybean oil, beeswax and extract powder and total volatile oil are mixed, obtain soft capsule content；5）Glycerine, water, ethyl hydroxy benzoate and gelatin are heated and mixed, obtains soft capsule shell glue；6）By step 4）Gained soft capsule content and step 5）The attached soft capsule of Chinese mugwort is prepared in gained soft capsule shell glue input encapsulating machine.The attached soft capsule dose of the Chinese mugwort is few, drug release rate is fast and stability is high, is alternatively arranged as anti-inflammatory drug.

Description

End attached soft capsule and its production method and application
Technical field
The invention belongs to technical field of medicine, and in particular to the attached soft capsule of one kind Chinese mugwort and its production method and application.
Background technology
Aifu nuangong pills, aifu nuangong wan prescription is by folium artemisiae argyi (charcoal) 120g, prepared RHIZOMA CYPERI with vinegar 240g, evodia rutaecarpa 80g processed, Chinese cassia tree 20g, Angelica sinensis 120g, Ligusticum wallichii 80g, Radix Paeoniae Alba (parched with wine) 80g, glutinous rehmannia 40g, astragalus root 80g and ten medicines of teasel root 60g composition (see：National Pharmacopeia committee member It can compile Pharmacopoeias of People's Republic of China (2015 editions) first, China Medical Science Press, 2015.), there is qi-regulating blood-nourishing, The effect of warm the womb menstruation regulating；For diseases such as the irregular menstruation caused by the deficiency of blood stagnation of the circulation of vital energy, the lower burnt cold of insufficiency type, dysmenorrhoea, Yao Xi Acid pains.《Middle traditional Chinese medicines Allusion quotation》Provide aifu nuangong pills, aifu nuangong wan preparation method：Ten Herbs in prescription are ground into fine powder, are sieved, add the refined honey of recipe quantity, are made big Honeyed bolus or small honey pill；Usage and dosage：Each 9g, it is 2-3 times daily.Aifu nuangong pills, aifu nuangong wan has dose, and (dose makes greatly with it greatly It is related with crude drug), be not easy to storage the shortcomings of.
The present invention keeps aifu nuangong pills, aifu nuangong wan flavour of a drug and recipe quantity constant, is developed into soft capsule, it is intended to reduces medicine clothes Dosage, accelerates medicine drug release rate, and improves the stability of medicine.In addition, the present invention is to soft capsule content and capsule shell material Material preferably, the attached soft capsule that ends is prepared for production and provides reference.
The content of the invention
Present invention aims to overcome that prior art defect, there is provided a kind of dose is few, the fast and stability of drug release property is high End attached soft capsule.
Present invention also offers the application of the production method of the attached soft capsule of above-mentioned Chinese mugwort, as well as anti-inflammatory drug.
To achieve the above object, the present invention adopts the following technical scheme that：
A kind of production method for the attached soft capsule that ends, it includes the following steps：
1) extraction of volatile oil：
Prepared RHIZOMA CYPERI with vinegar, evodia rutaecarpa, Chinese cassia tree, Angelica sinensis and the Ligusticum wallichii of recipe quantity are weighed, is crushed as powder, at room temperature with 8-12 weight Water again soaks 10-15h, then distills 6-7h using steam distillation, collects the volatile oil of layer waterborne in extractor, under Layer emulsifying part collects lower floor's oil droplet after adding a small amount of sodium chloride stirring, obtains total volatile oil；Residue in cucurbit is filtered, Obtain filter residue 1 and filtrate 1；
2) extraction at water-soluble position：
Weigh charred FOLIUM ARTEMISIAE ARGYI, Radix Paeoniae Alba, glutinous rehmannia, radix astragali, the teasel root of recipe quantity, at room temperature with the water of 8-12 times of weight immersion 1- 5h, is heated to slight boiling condition and decocts 30-60min, filtering, is extracted 1-3 time, merging filtrate, obtains filter residue 2 and filtrate 2；Will filter Liquid 1 and filtrate 2 mix, and are dried in vacuo after normal heating concentration, obtain medicinal extract 1；
3) the molten position extraction of alcohol：
After filter residue 1 is mixed with filter residue 2, is dried, weighing, with filter residue 1 and 40-60% second of 7-9 times of 2 gross weight of filter residue Alcohol solution heating slightly boiling extracts 20-40min, extracts 1-3 time, extracting solution is filtered, is mixed, recycle ethanol, gained thick paste It is dried in vacuo after normal pressure concentration, obtains medicinal extract 2；Medicinal extract 1 and medicinal extract 2 are denoted as extract powder；
4) preparation of soft capsule content：Soybean oil, beeswax and extract powder and total volatile oil are mixed, obtain soft capsule Content；
5) preparation of soft capsule shell glue：Glycerine, water, ethyl hydroxy benzoate and gelatin are heated and mixed, obtains soft capsule Shell glue；
6) preparation of soft capsule：By soft capsule shell glue input obtained by soft capsule content obtained by step 4) and step 5) The attached soft capsule of Chinese mugwort is prepared in encapsulating machine.
Step 4) is specially：Soybean oil 4.85kg and beeswax 138g are heated to being completely melt, mixes, cool down, added The extract powder 2.21kg of 120 mesh sieves, be put into homogeneous 10min on homogenizer, then adds total volatile oil 11ml, mixes, and crosses twice After colloid mill, homogeneous 10min, obtains soft capsule content, spare.
Step 5) is specially：Glycerine 2kg, water 5kg and ethyl hydroxy benzoate 5g are taken, the heating stirring in glue tank is changed, when temperature liter Gelatin 5kg swellings are put at up to 85 DEG C, are stirred continuously, 60 DEG C standing 4h, -0.08Mp vacuum outgas 30mins complete to swelling, Obtain soft capsule shell glue.
When preparing soft capsule in step 6), the technological parameter is controlled to be：50-60 DEG C of glue box temperature, sprinkler body temperature 35-37 DEG C, 16-18 DEG C, roller rotating speed 0.5r/min, mould rotating speed 1.5r/min of cryogenic temperature, adjusts both sides capsule shell thickness 0.7-0.9mm, after encapsulating machine is in stable condition, suppresses soft capsule, and through cooling down, it is dry, end attached soft capsule finished product to obtain the final product.
The present invention provides the attached soft capsule of Chinese mugwort being prepared using the above method.
Present invention also offers application of the attached soft capsule of above-mentioned Chinese mugwort in terms of anti-inflammatory drug is prepared.
Soft capsule is the domestic novel form just to have grown up in recent years, with loading amount is accurate, bioavilability is high, scattered Uniformly, it is easy to absorb after being disintegrated, convenient to take, good appearance, the advantages that patient is easily accepted by and uses.The formulation is in Chinese medicine preparation In application increasingly paid attention to, exploitation Chinese medicinal soft capsule become TCM modern preparations research hotspot.
The present invention is considered on the basis of original prescription proportioning, dis-medicinal part is removed, to reduce dose.For to greatest extent Active ingredient is preserved, after formulation ingredients are determined, Literature Consult is carried out to each medicinal material, specifies the active ingredient and its property of each medicinal material Matter, so as to facilitate design technology route.Prepared RHIZOMA CYPERI with vinegar, evodia rutaecarpa, Chinese cassia tree, Angelica sinensis, Ligusticum wallichii gomi herbs in aifu nuangong pills, aifu nuangong wan prescription Containing volatile oil active ingredient, to avoid the loss of volatile oil in processing procedure, first volatile oil extracting therein is come out, then Water carries respectively, alcohol extracting fully extracts active ingredient, to achieve the purpose that " discarding the dross and selecting the essential ".In present invention foundation prescription not The characteristics of with medicine, medicinal material of the part containing volatile oil component is individually extracted, then water carry, alcohol extracting, with ensure it is each effectively into The stability divided.
Content is uniform and stable before the forming for Chinese medicinal soft capsule, also to there is certain mobility, therefore present invention selection Uniformity, stability, sedimentation volume ratio are found through experiments that as inspection target：Extract powder, soybean oil, beeswax mass ratio are 1：2.2：0.0625, when medicinal extract Powder Particle Size is 120 mesh, obtained content is uniform and stable, good fluidity, easy to be molded.
In softgel shell preparation process, glue box temperature, sprinkler body temperature and cryogenic temperature can influence softgel shell quality.Glue box temperature mistake Height, glue easily adhere to glue box desiccation, cause the uneven even longitudinal cracking of shell thickness；The too low then glue of temperature flows out not smooth, capsule Thickness of the shell is uneven, rough surface.Sprinkler body temperature is excessive, and softgel shell is readily soluble disconnected, the yielding adhesion of soft capsule；Temperature is too low, content Easily aggregation caking, blocks nozzle.Cryogenic temperature is excessive, and glue easily flows on roller, and shell thickness is uneven, easily blocks refrigeration wind Machine；Temperature is too low, and softgel shell supercooling, vapor is easy to the liquefaction of softgel shell surface, causes the increase of softgel shell viscosity, inconvenient.Glue box temperature Degree and cryogenic temperature have considerable influence to softgel shell, should control -60 DEG C of glue box temperature 50 C, and cryogenic temperature is 16 DEG C -18 DEG C, refrigeration Temperature can suitably be adjusted according to room temperature, but temperature as low as droplet can not occur by roller, and otherwise softgel shell viscosity is too big, is unfavorable for grasping Make and be molded.Sprinkler body temperature not only influences softgel shell quality, also has an impact to content mobility, soft to ensure that softgel shell toughness is good Capsule loading amount is homogeneous, and sprinkler body temperature is normally identified as 35 DEG C -37 DEG C.
Brief description of the drawings
Fig. 1 is Y=(A, B) reciprocation response surfaces and contour map；
Fig. 2 is Y=(A, C) reciprocation response surfaces and contour map；
Fig. 3 is Y=(B, C) reciprocation response surfaces and contour map.
Embodiment
Technical scheme is further discussed in detail with reference to embodiments, but protection scope of the present invention It is not limited thereto.
1. instrument and material
1.1 experimental instrument and equipment
The full-automatic encapsulating machine of YWJ100-II types (Beijing Xinhangcheng Science ＆ Technology Development Co., Ltd.)；The encapsulated glue of temperature control type Plane supplies glue bucket (Beijing Xinhangcheng Science ＆ Technology Development Co., Ltd.)；(bright Medical Instruments is limited forever in Beijing for DZF-1 vacuum driers Company)；Volatile oil extractor (Nanjing Chemistry Reagent Co., Ltd.)；Electric jacket (Nanjing Cole's instrument experiment Co., Ltd)；Number Aobvious thermostat water bath (Shanghai Jiang Xing Instrument Ltd.)；Electric heating constant-temperature blowing drying box (the limited public affairs of the upper grand instrument and equipment of Nereid Department)；JML-100 colloid mills (Zhengzhou Yu Xiang mechanical equipments Co., Ltd)；Homogenizer.
1.2 experiment material
Prescription medicinal material [folium artemisiae argyi (charcoal), rhizoma cyperi (vinegar system), evodia rutaecarpa (system), Chinese cassia tree, Angelica sinensis, Ligusticum wallichii, Radix Paeoniae Alba (parched with wine), Huang, radix astragali (honey is processed), teasel root], beeswax (apiculture Co., Ltd of Beijing Tongrentang, lot number：20150202), soybean oil (Jiangxi benefit Pu Sheng pharmaceutcal corporation, Ltds), PEG400 (Shanghai Ling Feng chemical reagent Co., Ltd, lot number：20140821), gelatin (Luo Sailuo Gelatin Co., Ltd, lot number：2006444), glycerine (Suichang of Zhejiang Province Hui Kang pharmaceutcal corporation, Ltds), ethyl hydroxy benzoate (Hunan that health system Medicine limited company), atoleine (Chengdu Hua Yi pharmaceutic adjuvants manufacture Co., Ltd, lot number：20160401), water is Pure water.
2. method and result
The extraction of 2.1 volatile oil
Prepared RHIZOMA CYPERI with vinegar, evodia rutaecarpa, Chinese cassia tree, Angelica sinensis, the Ligusticum wallichii of recipe quantity are weighed, is crushed as coarse powder, at room temperature with 10 times of weight Water soaks 12h, then distills 6.5h using steam distillation, collects the volatile oil of layer waterborne in extractor, emulsification portion of lower floor Divide after adding a small amount of sodium chloride stirring and collect lower floor's oil droplet, obtain total volatile oil.Residue in cucurbit is filtered, obtains filter residue 1 With filtrate 1.
The extraction at 2.2 water-soluble positions
Weigh charred FOLIUM ARTEMISIAE ARGYI, Radix Paeoniae Alba, glutinous rehmannia, radix astragali, the teasel root of recipe quantity, at room temperature with 12 times of weight water immersion 1 it is small when, add Heat is to slight boiling condition and decocts 45min, and filtering (extraction is three times), gained filtrate will mix, and obtain filter residue 2 and filtrate 2 three times.Will filter Liquid 1 and filtrate 2 mix, and vacuum drying (pressure be -0.08kPa, 80 DEG C) after normal heating concentration, obtains medicinal extract 1.
The molten position extraction of 2.3 alcohol
Filter residue 1 is mixed with filter residue 2, dries, weighs, with filter residue 1 and 50% ethanol water of 8 times of 2 gross weight of filter residue Slightly boiling extraction 30min (extraction is twice) is heated, extracting solution will filter, mix twice, and put and recycle ethanol (temperature 45 on revolving instrument DEG C -50 DEG C), vacuum drying after the concentration of gained thick paste normal pressure (pressure be -0.08kPa, 80 DEG C), obtains medicinal extract 2.Medicinal extract 1 and medicinal extract 2 are denoted as extract powder.
2.4 content evaluation indexes and preferred (single factor exploration)
2.4.1 the establishment of evaluation index
1) uniformity：Extract powder and various auxiliary materials is taken to be mixed and stirred for, it is in suspension liquid to make it, and whether observation liquid mixes Uniformly, if having caking.10 points are full marks, are scored respectively.
2) mobility：By glass bar horizontal by 45 ° of placements, suspension is allowed, toward flowing down, to observe medicine above glass bar The situation that liquid drips.Scored respectively with wire, stable and uniform shape, drop-wise and lumps, 10 points are full marks.
3) sedimentation volume ratio：Take the suspension of same volume to be put into the graduated cylinder of same size, be uniformly mixed and stand 24h, Observation whether there is sedimentation, records the elemental height of liquid level and final height, calculates sedimentation volume ratio, sedimentation volume ratio is said closer to 1 Bright liquid is more stable.
2.4.2 content preparation method
The decentralized medium and suspending agent of recipe quantity are taken, 80 DEG C are heated to being completely melt, mix cooling, add recipe quantity mistake 120 mesh sieve extract powders, are put into homogeneous 10 minutes on homogenizer, to obtain the final product.
It is with the uniformity of mixture of extract powder and auxiliary material (30%), mobility (30%), sedimentation volume ratio (40%) Index, gives a mark respectively, and each index contribution margin is added in same sample, is the comprehensive grading of the sample, and such as the 2nd part of sample integrates Scoring=(6.0/8.0) × 30+ (8.0/8.0) × 30+ (0.72/0.95) × 40=82.82.
2.4.3 content prescription screening
2.4.3.1 the selection of decentralized medium
Soft capsule requires content as that can have certain mobility and good physics with the solution or suspension of encapsulated Stability.Common auxiliary material is produced according to soft capsule, selects three kinds of soybean oil, atoleine, polyethylene glycol 400 decentralized media to carry out Experiment, and scored according to evaluation index.As a result such as table 1
1 decentralized medium of table screens
Decentralized medium Suspending agent Uniformity Mobility Sedimentation volume ratio Scoring
Soybean oil Beeswax 8 8 0.95 100.00
Atoleine Beeswax 6 8 0.72 82.82
PEG400 Beeswax 7 8 0.85 92.04
From experimental result：In three kinds of decentralized media, content uniformity that soybean oil is prepared as decentralized medium and Mobility is preferable, and cheap, therefore is set to decentralized medium.
2.4.3.2 suspending agent screens
For ensure medicinal powder it is dispersed, store for a long time it is not stratified, be commonly incorporated into suspending agent ensure suspension stablize, soft capsule system Often selection beeswax lacks small toxicity as suspending agent, dosage during standby.
2.4.3.3 soybean oil dosage is investigated
Not same amount soybean oil is taken respectively, is handled by " 2.4.2 " item, adds recipe quantity beeswax and 120 mesh extract powders, the result is shown in Table 2.With twice of soybean oil of extract powder weight, obtained content is uniform and stable, good fluidity, and state is optimal.
2 soybean oil dosage of table is investigated
Numbering Soybean oil:Cream powder Beeswax:Cream powder Granularity/mesh Scoring
1 1：1 1：10 120 67.90
2 1.5：1 1：10 120 75.05
3 2：1 1：10 120 85.72
4 2.5：1 1：10 120 85.02
5 3：1 1：10 120 68.05
2.4.3.4 suspending agent dosage is investigated
Not same amount beeswax is taken respectively, is handled by " 2.4.2 " item, adds recipe quantity soybean oil and 120 mesh extract powders, the result is shown in Table 3.With beeswax:Cream powder=1:15 mass ratio addition, suspending best results, obtained content is uniform and stable, good fluidity.
3 suspending agent dosage of table is investigated
Numbering Soybean oil:Medicinal powder Beeswax:Cream powder Granularity/mesh Scoring
1 2：1 1：5 120 82.14
2 2：1 1：10 120 86.53
3 2：1 1：15 120 88.03
4 2：1 1：20 120 85.44
5 2：1 1；25 120 70.50
2.4.3.5 medicinal powder granularity is investigated
Varigrained extract powder is taken respectively, is handled by " 2.4.2 " item, adds recipe quantity soybean oil and beeswax, the result is shown in Table 4.Optimal with 120 mesh granularity content material states, i.e., obtained content is uniform and stable, good fluidity.
4 medicinal extract Powder Particle Size of table is investigated
Numbering Soybean oil:Medicinal powder Beeswax:Medicinal powder Granularity/mesh Scoring
1 2：1 1：15 80 65.4
2 2：1 1：15 100 77.12
3 2：1 1：15 120 85.03
4 2：1 1：15 140 82.44
5 2：1 1：15 200 70.50
2.4.4 response surface optimization preparation process
2.4.4.1 response surface design and result
To determine the best prescription proportioning of the attached soft capsule of Chinese mugwort, according to the central combination design principle of Box-Behnken, It is from change that medicine is chosen on the basis of single factor experiment with substrate composition (A), suspending agent and drug ratio (B), medicinal powder particle diameter (C) Amount, content comprehensive grading (Y) is response, and the response of Three factors-levels is carried out by 8.0 softwares of Design-Expert Face experimental design, to analysis of experimental data processing, founding mathematical models, determine that best prescription matches.Response surface empirical factor water Flat table is shown in Table 5.Box-Behnken experimental designs and it the results are shown in Table 6.The variance analysis of regression model is shown in Table 7.
5 response surface empirical factor level code table of table
6 Box-Behnken experimental designs of table and result
The variance analysis of 7 regression model of table
Regression analysis is carried out by 8.0 softwares of Design-Expert, is obtained between each factor and content comprehensive grading Polynary quadratic regression equation：Y=88.41-0.78A+3.27B+2.34C+1.61AB-0.35AC-0.5BC-5.21A2- 4.77B2-4.22C2。
As seen from Table 7：Model has conspicuousness (P in experiment<0.0001), illustrate that the model has statistical significance. Each factor and response relation significantly (R in regression equation2=0.9840), illustrating the change of response has 98.4% to derive from institute Variable is selected, and tests first order B, C and quadratic term A in established fit equation2、B2、C2There is pole significant difference (P with model <0.01), lose plan item P=0.1437 and do not have conspicuousness, show that equation is preferable to the fitting degree of experiment, which can be predicted Content optimum preparating condition.
It can be seen that from fit equation：Medicine has content negatively influencing, suspending agent and drug ratio with substrate composition (A) (B) and medicinal powder granularity (C) is in active influence to content, and three is B ＞ C ＞ A to the influence degree of content, and wherein suspending agent is used Amount and influence of the medicinal powder granularity to content are extremely notable.
2.4.4.2 factor reciprocation
The reciprocation of 3 factors influential on soft capsule content comprehensive grading is analyzed, respectively obtain it is each because The response surface and contour map of the reciprocation relation of element, are shown in Fig. 1, Fig. 2, Fig. 3.
As shown in Figure 1, the change of A and B can all make content comprehensive grading that gentle domatic change be presented, and contour is in ellipse Circle, illustrates both to have a certain impact to the comprehensive grading of content.When A or B are determined, the gradient of A is substantially gently in B The gradient, short axle illustrates that influences of the B to content comprehensive grading is more than A on the contour of A.Compared to Fig. 2 and 3, Fig. 1's Contour distribution tends to ellipse, illustrates that the influence that content is scored in the interaction between A, B is notable.And Fig. 2, Fig. 3 In contour close to circle, illustrate that substrates quantity is not shown with cream Powder Particle Size and suspending agent dosage and the reciprocation of medicinal powder granularity Write.
2.4.4.3 confirmatory experiment result
By Design-Expert software analysis, simulation show that the highest optimum organization of embedding rate is A=1：2.24, B= 1：16.62nd, C=125.13, i.e. medicine and substrate composition 1：2.24th, suspending agent and drug ratio 1：16.62, medicinal powder particle diameter During 125.13 mesh, the content comprehensive grading of preparation is up to 89.2529.For the facility of practical operation, by optimised process bar Part is modified to medicine and substrate composition 1：2.2nd, suspending agent and drug ratio 1：16th, 120 mesh of medicinal powder particle diameter, carries out repeated three times Experiment, the microcapsules efficiency measured three times is averaged, is as a result (88.55 ± 0.89), and predicted value is approached with actual value, is rung Answer face optimum results reliable.It is feasible using the attached soft capsule content technique of response surface optimization Chinese mugwort.
2.5 softgel shell prescription is preferred
The primary raw material of soft capsule shell is gelatin and water, is commonly incorporated into glycerine and is usually as plasticizer, three's mass ratio Gelatin：Glycerine：Water=1：0.4-0.6：1, to prevent from going mouldy, 0.1% ethyl hydroxy benzoate, ethylparaben etc. are commonly incorporated into as antibacterial Agent.2.5.1 the preparation process of softgel shell
The glycerine, water and ethyl hydroxy benzoate of recipe quantity are taken, the heating stirring in glue tank is changed, puts into when temperature is increased to 85 DEG C The gelatin swelling of recipe quantity, it is complete to being swollen to be stirred continuously 3-5h, 60 DEG C stand 4 it is small when after, vacuum pressure pump exhaust bubble, is protected Temperature, it is spare.
2.5.1.1 softgel shell proportioning screening
With the toughness of softgel shell and viscosity for inspection target, gelatin, glycerine, water three different quality are investigated with comparison softgel shell Influence, the results are shown in Table 8.The results show：Gelatin：Glycerine：Water=1：0.4：Softgel shell is optimal made from 1.
8 softgel shell different ratio of table is investigated
Different ratio Toughness Viscosity
1：0.3：1 Difference Generally
1：0.4：1 It is good It is good
1：0.5：1 Generally It is good
1：0.6：1 Generally It is poor
1：0.7：1 Difference It is very poor
2.5.1.2 temperature is screened
Glue box temperature, sprinkler body temperature and cryogenic temperature in preparation process can influence softgel shell quality.Found through experiment：Room 25 DEG C of temperature, indoor humidity control -60 DEG C of glue box temperature 50 C, 35 DEG C -37 DEG C of sprinkler body temperature, cryogenic temperature under the conditions of being 60%RH At 16 DEG C -18 DEG C, obtained softgel shell character is optimal, is easy to preparations shaping.
2.6 soft capsule preparation processes
By gelatin：Glycerine：Water=1：0.4：1 ratio, takes the glycerine, water and ethyl hydroxy benzoate of recipe quantity, in glue tank is changed Heating stirring, the gelatin swelling of recipe quantity is put into when temperature is increased to 85 DEG C, is stirred continuously 3-5h to being swollen completely, 60 DEG C quiet Put 4 it is small when, -0.08Mp, vacuum outgas 30min.Content presses " 2.4.3.3 " item preferred proportion, according to the method for " 2.4.2 " item Prepare, add volatile oil, mix, after crossing twice of colloid mill, homogeneous 10min, is placed in encapsulating machine, opens power supply, adjusts work Skill parameter：Glue box temperature：55 DEG C, 36 DEG C of sprinkler body temperature, 17 DEG C of cryogenic temperature, roller rotating speed 0.5, mould rotating speed 1.5, adjustment two Side rubber thickness 0.7-0.9mm, after machine is in stable condition, suppresses soft capsule, the soft capsule prepared is transferred to rotating cage, and Wind turbine and rotating cage are opened, is allowed to cool, is dry, getting product.
To investigate technology stability, empirically optimum condition has carried out following pilot experiments：
1) preparation of soft capsule content：Input soybean oil 4.85kg, beeswax 138g are heated to being completely melt, mix, is cold But, the extract powder 2.21kg of 120 mesh sieves was added, is put into homogeneous 10min on homogenizer, then adds total volatile oil 11ml, was mixed Even, after crossing twice of colloid mill, homogeneous 10min, obtains soft capsule content, content is in dark brown brown, spare；
2) preparation of soft capsule shell glue：Glycerine 2kg, water 5kg and ethyl hydroxy benzoate 5g are taken, heats and stirs in glue tank is changed Mix, gelatin 5kg swellings are put into when temperature is increased to 85 DEG C, be stirred continuously to swelling completely, 60 DEG C of standings 4h, -0.08Mp are true Sky degassing 30min, obtains soft capsule shell glue；
3) preparation of soft capsule：By soft capsule shell glue input obtained by soft capsule content obtained by step 1) and step 2) The attached soft capsule of Chinese mugwort is prepared in encapsulating machine (controls the technological parameter to be：55 DEG C of glue box temperature, 36 DEG C of sprinkler body temperature, refrigeration temperature 17 DEG C, roller rotating speed 0.5r/min, mould rotating speed 1.5r/min of degree, adjusts 0.7-0.9mm of both sides capsule shell thickness, treats soft After capsule machine is in stable condition, suppress soft capsule, and through cooling down, it is dry, end attached soft capsule finished product to obtain the final product).About prepare soft capsule 9000, ratio of briquetting about 90%.The attached soft capsule loading amount of Chinese mugwort prepared is 0.8g, is provided according to Chinese Pharmacopoeia, content uniformity symbol States Pharmacopoeia specifications are closed, every is equipped with 0.24g extract powders, and beeswax amount is 0.015g, soybean oil 0.5264g, and volatile oil content is 0.75 μ l, every is 1.41g equivalent to crude drug amount.Provided by the usage and dosage of aifu nuangong pills, aifu nuangong wan, the attached soft capsule of Chinese mugwort after improvement Usage and dosage is：Three times per day, once two grains；Compared to former pill, dose greatly reduces.
The attached soft capsule that ends to the above-mentioned present invention being prepared has carried out following related tests of pesticide effectiveness.
1. analgesic test
Influence (writhing test) of the 1.1 attached soft capsules of Chinese mugwort to glacial acetic acid induced mice writhing number
Mouse 60, half male and half female, 22 ± 2g of weight, is randomly divided into 6 groups, every group 12.1. blank control group：Give big Soya-bean oil；2. positive controls 1：Aspirin group 10mg/ml；Positive controls 2：Give aifu nuangong pills, aifu nuangong wan 0.2g/ml；3. it is attached to end Soft capsule administration group：High dose group 3.64g/kg, middle dose group 1.82g/kg；Low amounts group 0.91g/kg, drug concentration are respectively 181.99mg/ml, 90.995mg/ml, 45.4975mg/ml, equivalent to 10 times, 5 times, 2.5 times of dose,equivalent.Volume, which is administered, is 0.2ml/10g weight, once a day, successive administration 6 days, fasting for solids but not liquids 12h before last dose, 30min, divides after the last administration 0.7% glacial acetic acid solution 0.2ml/ is not injected intraperitoneally only, observes and records the animal writhing number occurred in 20min immediately and go out The number of animals of existing writhing response, the analgesia percentage of administration group is calculated by following equation.
Influence (X ± SD, n=12) of the table 9 to glacial acetic acid induced mice writhing response
Packet Dosage (g/kg) Writhing number Analgesia rate %
Blank control group / 22.2±9.6 /
Positive drug group 1 0.2 5.8±5.1** 73.87
Positive drug group 2 4 13.8±6.9* 37.84
Low dose group 0.91 21.0±6.3 0.05
Middle dose group 1.82 15.7±8.3 29.27
Advanced amount group 3.64 13.7±4.9* 38.29
Note：* p ＜ 0.05；* p ＜ 0.01vs control, it is the same below
As can be seen from Table 9：The basic, normal, high dosage group of attached soft capsule that ends can reduce mouse writhing number, wherein high dose Measure statistically significant (p ＜ 0.05), analgesia rate increases and increases with drug dose.
Influence (hot-plate) of the 1.2 attached soft capsules of Chinese mugwort to thermostimulation induced mice pain
Take female mice, using intelligent hot-plate instrument replication mouse normal pain threshold twice, choose Basic Pain Threshold 5~ Mouse between 30 seconds 50,20 ± 2g of weight, 5 groups, every group 10 are randomly divided into by the threshold of pain.Packet and dosage are same as above, Once a day, successive administration 5 days, measure the threshold of pain in 60 minutes after the last administration.Record mouse is from hot plate is put into occurring licking metapedes Pain threshold of the time (second) as the mouse, METHOD FOR CONTINUOUS DETERMINATION 2 times, if pain threshold more than 60 seconds, in terms of 60 seconds.It the results are shown in Table 10。
Influence (X ± SD, n=10) of the table 10 to thermostimulation induced mice pain
Packet Dosage (g/kg) The threshold of pain time (s)
Blank control group / 13.21±4.46
Positive drug group 1 0.2 16.78±3.88**
Low dose group 0.91 18.08±5.36**
Middle dose group 1.82 19.26±4.94**
Advanced amount group 3.64 22.22±7.04**
The result shows that：The basic, normal, high dosage group of attached soft capsule that ends can dramatically increase the mouse threshold of pain time (p ＜ 0.01), Extending the threshold of pain time increases and increases with drug dose, and analgesic effect is better than positive drug group.
2 anti-inflammatories test (new discovery)
The influence of 2.1 attached warm the womb soft capsule paraxylene induced mice ear swellings
Mouse 50, weight 18-22g is taken, half male and half female, is randomly divided into 5 groups, every group 10.Positive controls：Give cloth Ibuprofen 8mg/ml；The dosage of blank control group and high, medium and low dosage administration group is same as above 1.1.Once a day, successive administration 6 My god, fasting for solids but not liquids 12h before last dose, after the last administration 30min, two sides applies dimethylbenzene 0.02 before and after mouse right ear respectively Milliliter/only, left ear is without any processing.Animal cervical dislocation is put to death after 4h, two ears are cut along auricle substrate, with 9 millimeters of diameter Card punch, lays round auricle at same position respectively, weighs.Respectively swelling, swelling rate and suppression are calculated by following calculation formula Rate processed.
Swelling (%)=auris dextra piece weight-left auricle weight；
The influence (X ± SD, n=10) of 11 paraxylene induced mice ear swelling of table
Packet Dosage (g/kg) Swelling Swelling rate % Inhibiting rate %
Blank control group / 0.0060±0.0025 58.21±14.08 /
Positive controls 0.16 0.0059±0.0014 43.28±6.67** 25.65
Low dose group 0.91 0.0060±0.0023 48.87±16.85 16.05
Middle dose group 1.82 0.0047±0.0013 40.31±11.69** 30.75
Advanced amount group 3.64 0.0036±0.0012* 31.39±12.08** 46.07
As can be seen from Table 11：Compared with blank control group, the basic, normal, high dosage group of attached soft capsule that ends and positive drug group are equal Swelling rate can be reduced, positive drug group, middle dose group and high dose group are statistically significant (p ＜ 0.01)；To mice ear Inhibiting rate with drug dose increase and increase.Test result indicates that：The attached soft capsule of medicine Chinese mugwort of the present invention has preferable anti-inflammatory to make With.
2.2 abdominal cavity dyestuff exudation methods
Abdominal cavity dyestuff exudation method：Take mouse 50, weight 18-22g, half male and half female is randomly divided into 5 groups, every group 10, sun Property control group：Give brufen 8mg/ml；Remaining packet and dosage are same as above.Once a day, successive administration eight days.Last is given Fasting for solids but not liquids 12h before medicine, after the last administration 60min, the Evans blue 0.25ml/ of tail vein injection 0.5% only, i.e. 0.1ml/ 10g, is then injected intraperitoneally 0.7% 0.2ml/, glacial acetic acid, cervical dislocation is put to death after 20min, with 6ml normal saline flushing abdomens Chamber, is gently rubbed, and suctions out intraperitoneal cleaning solution, adds physiological saline to 10ml in collecting pipe after merging, 3000rpm, 15min centrifugation, Supernatant colorimetric estimation OD values under 590nm, the dye of every mouse peritoneal infiltration is looked into then at Evans blue OD values-concentration standard curve Doses.It the results are shown in Table 12.
Influence (X ± SD, n=10) of the table 12 to mouse peritoneal dyestuff seepage discharge
Packet Dosage (g/kg) Dyestuff seepage discharge (ug/ml)
Blank control group / 2.589±0.817
Positive controls 0.16 2.294±0.902
Low dose group 0.91 2.615±0.930
Middle dose group 1.82 2.252±0.625
Advanced amount group 3.64 0.710±0.319**
The result shows that：Compared with blank control group, the basic, normal, high dosage group of Aifunuangong soft capsule and positive drug group are equal for this Abdominal cavity dyestuff seepage discharge can be reduced, wherein high dose group is statistically significant (p ＜ 0.01)；There is the obvious work for suppressing inflammatory exudation With.The influence of 3 pairs of underage mouses
Female mouse 50,11~13g of weight, is randomly divided into 5 groups, every group 10, positive controls：It is attached warm to give Chinese mugwort Palace ball 0.2g/ml；Remaining packet and dosage are same as above..Once a day, successive administration 14 days.Fasting can't help before last dose Water 12h, after the last administration 30min, retroorbital venous clump take blood, then put to death mouse, uterus and ovary are won, rapidly in precision Weigh on electronic scale, calculate mouse ovarian and Uterine coefficient.Enzyme-linked immunization (ELISA method) method measures serum estradiol content. In units of g, organ coefficient is represented organ weights with organ weights/weight × 100%.It the results are shown in Table 13,14.
Influence (X ± SD, n=10) of the table 13 to underage mouse serum estradiol
Influence (X ± SD, n=10) of the table 14 to underage mouse ovary, uterus
The result shows that：The attached basic, normal, high dosage group of soft capsule of present invention Chinese mugwort can increase underage mouse serum estradiol and contain Amount, wherein low dose group has significant difference (p ＜ 0.05), and middle and high dosage group has significant difference (p ＜ 0.01).Another dissection It was found that：The attached basic, normal, high dosage group of soft capsule of present invention Chinese mugwort can increase underage mouse ovary, the wherein weight in uterus, high dose Uterine coefficient has significant difference (p ＜ 0.01).
Irregular menstruation is often developed with female reproductive system, and the change of female hormone and the functional status in uterus are related, Chinese mugwort Attached soft capsule can make underage mouse uterus, ovarian weight augmentation, increase serum estradiol content, show that the medical instrument has similar estrogen Sample acts on, or has the function that to promote hypothalamic-pituitary-ovarian axis at the same time；It can make endometrial hyperplasia, promote the menstrual cycle Change, this provides theoretical foundation for clinical treatment irregular menstruation.
The influence of 4 pairs of dysmenorrhea model in mice
Female mice 50, weight 18-22g is taken, is randomly divided into five groups, every group 10, positive controls：Give Bu Luo It is fragrant；Model group：Give Estradiol Valerate；The dosage of blank control group and high, medium and low dosage administration group is same as above 1.1.Daily Once, successive administration 10 days, are administered volume 0.2ml/10g weight.The 1-10 days morning dose Estradiol Valerates of modeling medicine, and it is first Secondary dosage doubles (0.4ml/ is only), and the attached soft capsule various concentrations liquid of Chinese mugwort and the positive were given once daily since the 6th day afternoon Medicine etc..After last dose 40min, intraperitoneal injection oxytocins 1u/ only, after 5min, records the animal writhing number occurred in 30min And there is the number of animals of writhing number, the analgesia percentage of administration group is calculated according to the following formula：By each group mouse after 30min Pluck eyeball and take blood, 1500rpm, centrifuges 15min, take serum, spare.
Influence (x ± s, n=10) of the table 15 to the writhing response of dysmenorrhea model in mice
Packet Dosage (g/kg) Writhing number Analgesia rate %
Blank control group / 24.3±5.4 /
Positive controls 0.16 14.3±5.8* 41.1
Low dose group 0.91 18.9±6.0 22.2
Middle dose group 1.82 17.3±5.2 28.8
Advanced amount group 3.64 15.2±4.8* 37.4
As can be seen from Table 15：Compared with model group, the attached basic, normal, high dosage group of soft capsule of present invention Chinese mugwort can substantially reduce Dysmenorrhoea mouse writhing reaction times, and be in dose dependent.
The effect of Rat Experimental dysmenorrhea model caused by 5 pairs of oxytocins：
Rat 70 is taken, is randomly divided into 7 groups, every group 10.Negative control group, model group, positive drug group (positive drug group 1： Give brufen；Positive drug group 2：Give aifu nuangong pills, aifu nuangong wan), the attached soft capsule low dose group (0.405g/kg) of Chinese mugwort, middle dose group (0.819g/kg), high dose group (1.638g/kg).Model reference literature is prepared (such as：Liu Jin, waits applications Rat Experimental pain Stop analgesic activity [J] experimental animals and the comparative medicine of emplastrum, 2015,35 (2) through model evaluation dysmenorrhoea：167-169；It is old Strange chief editor:Herbal pharmacology research methodology (the 3rd edition) Beijing:People's Health Publisher, 2011:1205).Except negative control Group is outer, and the equal gavage of every rat of remaining each group gives Progynova (estradiol valerate tablet), once a day (first day administration 0.2mg Every, second day to the 9th day 0.1mg every, the tenth day 0.2mg every).Start within 5th day, gastric infusion, negative control group Equivalent soybean oil is given with model group, remaining each group gastric infusion.Last give Progynova 24 it is small when after, when last dose 1 is small Afterwards, each group rats by intraperitoneal injection oxytocins 2u/ only, observes the pain reaction of rat in 30 minutes, strong by uterus of writhing response The index (dysmenorrhoea) of strong contraction, observes animal writhing number (rat abdomen indent, trunk and hindlimb extension, buttocks and side limb Rotation in vivo).After observation, rat is anaesthetized with 8% urethane, abdominal aortic blood, anti-freezing, takes serum, and -20 DEG C of preservations are standby With enzyme-linked immunization (ELISA method) measure TXB2, 6-keto-Fl α, the content of β-EP；Take anti-freezing hematometry hemorheology.
The influence of 5.1 pairs of pain writhing responses
Influence of the table 16 to writhing response caused by pain
Packet Dosage (g/kg) Writhing number Analgesia rate %
Blank control group / / /
Model group / 13.4±4.0 /
Positive drug group 1 0.2 3.3±2.3** 75.37
Positive drug group 2 2.0 6.5±4.2* 51.49
Low dose group 0.405 9.2±3.6 31.3
Middle dose group 0.819 4.1±1.8** 69.40
Advanced amount group 1.638 3.2±1.5** 76.11
Note：The * p ＜ 0.05 compared with model group；* p ＜ 0.01
As can be seen from Table 16：Compared with model group, it is big that the basic, normal, high dosage group of attached soft capsule that ends can substantially reduce dysmenorrhoea Mouse writhing response number.
Dysmenorrhea model rat blood TXB caused by 5.2 pairs of oxytocins2, 6-keto-Fl alpha contents influence
17 Aifunuangong soft capsule of table is to dysmenorrhea model rat blood TXB2, 6-keto-Fl ɑ contents influence (x ± s, n =10)
Packet Dosage (g/kg) TXB2 6-keto-Flɑ TXB2/6-keto-Flɑ
Blank control group / 42.17±6.14 252.65±91.24 0.1669
Model group / 48.90±6.91## 157.19±51.85# 0.3110
Positive drug group 1 0.2 37.36±6.82** 164.24±77.65 0.2271
Positive drug group 2 2.0 38.54±8.57** 190.92±59.34 0.2019
Low dose group 0.405 39.79±6.43** 201.77±57.80 0.1972
Middle dose group 0.819 38.26±6.09** 210.01±72.93 0.1822
Advanced amount group 1.638 35.01±2.33** 220.02±72.86* 0.1591
Note：The ##p ＜ 0.01 compared with blank control group；The * p ＜ 0.05 compared with model group, * * p ＜ 0.01
As can be seen from Table 17：Model group rats serum T XB2Content increases (p ＜ 0.01), and 6-keto-Fl alpha contents reduce (p ＜ 0.05), TXB2/ 6-keto-Fl α ratios increase.Compared with model group, end the basic, normal, high dosage group of attached soft capsule and the positive Medicine group 1,2 can make TXB2Content significantly reduces (p ＜ 0.01)；The 6-keto-Fl alpha contents increase of positive drug group 1,2, but do not have Statistical significance, the basic, normal, high dosage group of attached soft capsule that ends can increase 6-keto-Fl alpha contents, and wherein high dose group has statistics Learn meaning (p ＜ 0.05), TXB2/ 6-keto-Fl α ratios increase and reduce with drug dose.
The influence of dysmenorrhea model rat blood β-EP contents caused by 5.3 pairs of oxytocins
Influence (x ± s, n=10) of the 18 Aifunuangong soft capsule of table to dysmenorrhea model rat blood β-EP contents
Packet Dosage (g/kg) β-EP
Blank control group / 105.38±23.45
Model group / 63.56±25.51##
Positive drug group 1 0.2 104.30±30.01**
Positive drug group 2 2.0 87.22±26.23
Low dose group 0.405 87.22±26.23*
Middle dose group 0.819 88.42±21.38*
Advanced amount group 1.638 93.43±20.71**
Note：The ##p ＜ 0.01 compared with blank control group；The * p ＜ 0.05 compared with model group, * * p ＜ 0.01
As can be seen from Table 18：Model group rats serumβ-EP contents significantly reduce (p ＜ 0.01).Compared with model group, The basic, normal, high dosage group of attached soft capsule that ends and positive drug group 1,2 can increase the content of β-EP, and wherein positive drug group 1 has statistics Meaning (p ＜ 0.01), 2 no difference of science of statistics of positive drug group；The attached soft capsule that ends is low, middle dose group difference is obvious (p ＜ 0.05), high Dosage group has significant difference (p ＜ 0.01).
The influence of dysmenorrhea model hemorheology of rat caused by 5.4 pairs of oxytocins
Influence of the 19 Aifunuangong soft capsule of table to dysmenorrhea model hemorheology of rat
Note：The ##p ＜ 0.01 compared with blank control group；The * p ＜ 0.05 compared with model group, * * p ＜ 0.01
Influence of the 20 Aifunuangong soft capsule of table to dysmenorrhea model hemorheology of rat
Note：The ##p ＜ 0.01 compared with blank control group；The * p ＜ 0.05 compared with model group, * * p ＜ 0.01
It can be seen that by table 19 and 20：It is model group rats plasma viscosity, packed cell volume, complete compared with blank control group Blood undercut relative indices, whole blood height, which cut relative indices, erythrocyte aggregation index, whole blood undercut reduced viscosity, notable difference (p ＜ 0.05)；Reduction viscosity of blood, erythrocyte mechanical fragility no difference of science of statistics.Compared with model group, end attached soft capsule Basic, normal, high dosage group and positive drug group 1,2 can obviously improve hemorheology index, and the attached soft capsule that ends increases with drug dose Add, improve hemorheological indexes, in dose dependent, such as reduce plasma viscosity.Show：Ending attached soft capsule can be bright Aobvious glutinous, dense, the poly- state for improving Dysmenorrhea Rats blood, has the function of tonifying blood and regulating menstruation.

Claims (6)

1. a kind of production method for the attached soft capsule that ends, it is characterised in that include the following steps：
1）The extraction of volatile oil：
Prepared RHIZOMA CYPERI with vinegar, evodia rutaecarpa, Chinese cassia tree, Angelica sinensis and the Ligusticum wallichii of recipe quantity are weighed, is crushed as powder, at room temperature with 8-12 times of weight Water soaks 10-15h, then distills 6-7h using steam distillation, collects the volatile oil of layer waterborne in extractor, lower floor's breast Change after part adds a small amount of sodium chloride stirring and collect lower floor's oil droplet, obtain total volatile oil；Residue in cucurbit is filtered, must be filtered Slag 1 and filtrate 1；
2）The extraction at water-soluble position：
Charred FOLIUM ARTEMISIAE ARGYI, Radix Paeoniae Alba, glutinous rehmannia, radix astragali, the teasel root of recipe quantity are weighed, soaks 1-5h with the water of 8-12 times of weight at room temperature, It is heated to slight boiling condition and decocts 30-60min, filtering, is extracted 1-3 time, merging filtrate, obtains filter residue 2 and filtrate 2；By filtrate 1 Mixed with filtrate 2, be dried in vacuo after normal heating concentration, obtain medicinal extract 1；
3）The molten position extraction of alcohol：
After filter residue 1 is mixed with filter residue 2, is dried, weighing, with filter residue 1 and 40-60% ethanol waters of 7-9 times of 2 gross weight of filter residue Solution heating slightly boiling extracts 20-40min, extracts 1-3 time, extracting solution is filtered, is mixed, recycle ethanol, gained thick paste normal pressure It is dried in vacuo after concentration, obtains medicinal extract 2；Medicinal extract 1 and medicinal extract 2 are denoted as extract powder；
4）The preparation of soft capsule content：Soybean oil, beeswax and extract powder and total volatile oil are mixed, obtain soft capsule content Thing；
5）The preparation of soft capsule shell glue：Glycerine, water, ethyl hydroxy benzoate and gelatin are heated and mixed, obtains soft capsule shell glue Liquid；
6）The preparation of soft capsule：By step 4）Gained soft capsule content and step 5）Gained soft capsule shell glue puts into flexible glue The attached soft capsule of Chinese mugwort is prepared in capsule machine.
2. the production method for the attached soft capsule that ends as claimed in claim 1, it is characterised in that step 4）Specially：By soybean oil 4.85 kg and beeswax 138g are heated to being completely melt, mix, cool down, and add 2.21 kg of extract powder of 120 mesh sieves, are put into Homogeneous 10min on matter machine, then adds total volatile oil 11ml, mixes, and after crossing twice of colloid mill, homogeneous 10min, obtains soft capsule Content, it is spare.
3. the production method for the attached soft capsule that ends as claimed in claim 1, it is characterised in that step 5）Specially：Take glycerine 2kg, Water 5kg and ethyl hydroxy benzoate 5g, the heating stirring in glue tank is changed, gelatin 5kg swellings are put into when temperature is increased to 85 DEG C, are constantly stirred Mix, 60 DEG C standing 4h, -0.08Mp vacuum outgas 30mins complete to swelling, acquisition soft capsule shell glue.
4. the production method for the attached soft capsule that ends as claimed in claim 1, it is characterised in that step 6）In when preparing soft capsule, control Technological parameter processed is：50-60 DEG C of glue box temperature, 35-37 DEG C of sprinkler body temperature, 16-18 DEG C of cryogenic temperature, roller rotating speed 0.5r/ Min, mould rotating speed 1.5r/min, adjust 0.7-0.9mm of both sides capsule shell thickness, after encapsulating machine is in stable condition, compacting Soft capsule, and through cooling down, it is dry, end attached soft capsule finished product to obtain the final product.
5. the attached soft capsule of Chinese mugwort being prepared using any the method for Claims 1-4.
6. application of the attached soft capsule of Chinese mugwort as anti-inflammatory drug described in claim 5.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112932971A (en) * 2021-03-04 2021-06-11 江西思乡农业有限公司 Rhizoma polygonati processing device and processing method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050024514A (en) * 2003-09-01 2005-03-10 박정숙 Composition containing Alpiniae Semen and Pueraria Flower
CN101474276A (en) * 2008-12-31 2009-07-08 四川禾邦阳光制药股份有限公司 Soft capsule preparation with function for dissolving breast mass and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050024514A (en) * 2003-09-01 2005-03-10 박정숙 Composition containing Alpiniae Semen and Pueraria Flower
CN101474276A (en) * 2008-12-31 2009-07-08 四川禾邦阳光制药股份有限公司 Soft capsule preparation with function for dissolving breast mass and preparation method thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
卢祥之: "《中华养生茶》", 31 July 2013, 人民军医出版社 *
程东岩等: ""艾附暖宫颗粒挥发油提取工艺的研究"", 《中国实验方剂学杂志》 *
蓝太富等: "《家庭常见成药（修订本）》", 31 May 1991, 四川科学技术出版社 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112932971A (en) * 2021-03-04 2021-06-11 江西思乡农业有限公司 Rhizoma polygonati processing device and processing method thereof
CN112932971B (en) * 2021-03-04 2022-12-02 江西省思乡赣品绿色食品有限公司 Rhizoma polygonati processing device and processing method thereof

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